PMID- 9168608
TI  - Resuscitation of 'non-culturable' cells from aged cultures of Campylobacter
      jejuni.
AB  - When stationary phase batch cultures of Campylobacter jejuni were stored in
      sealed flasks under static conditions, viable numbers declined from 2 x 10(9)
      c.f.u. ml-1 to around 10(3)-10(6) c.f.u. ml-1 within 4-6 weeks. When the aged
      cultures were sparged with a microaerobic gas mixture, there was a rapid increase
      in viable numbers accompanied by a change from predominantly coccoid to vibrioid
      morphology. The most probable number (MPN) technique was used to distinguish
      resuscitation of injured or dormant cells from multiplication of residual viable
      cells. MPN estimates using fresh Brucella broth containing 0.2% mucin revealed
      that plate counts underestimated the true viable count by up to 23-fold. The
      experiments clearly demonstrated that a proportion of surviving cells in aged
      cultures were in an injured or latent state that prevented growth on agar plates.
      It is possible that the size of this fraction is greater than was demonstrated
      and that much higher recoveries would be obtained under other recovery
      conditions. Nevertheless, from presently available evidence, it must be concluded
      that the size of the latent fraction is quite small and that most of the increase
      in count that occurs on regassing a spent culture comes from multiplication of
      residual viable cells.

PMID- 9168609
TI  - Inhibition of Paracoccidioides brasiliensis by ajoene is associated with blockade
      of phosphatidylcholine biosynthesis.
AB  - In Paracoccidioides brasiliensis, a dimorphic fungus pathogenic for humans, no
      significant differences were observed in the phospholipid species of both
      morphological phases. The species observed were phosphatidylcholine (PC, 30-40%),
      phosphatidylethanolamine (PE, 27-28%), phosphatidylserine (16-19%),
      phosphatidylinositol (13-17%) and sphingomyelin (3-5%). The main fatty acids
      found in the yeast (Y) phase were palmitate (56%), linoleate (18%) and oleate
      (15%), while linoleate predominated (61%) in the mycelial (M) phase, followed by
      palmitate (27%) and oleate (7%). In the Y phase the main free sterol was ergosta
      5,22-dien-3 beta-ol (82%) plus some lanosterol (12%) and ergosterol (6%), while
      in the M phase, the latter predominated (88%), followed by low levels of ergosta
      5,22-dien-3 beta-ol (12%). Ajoene [(E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9
      oxide], a platelet aggregation inhibitor derived from garlic, induced alterations
      in phospholipid and fatty acid proportions such that PC was reduced to about 18%
      in both phases and PE increased to 38% (Y phase) or 44% (M phase), suggesting
      inhibition of PC synthesis. Ajoene also reduced saturated fatty acids (16:0 and
      18:0) from 67 to 35% in the Y phase, with a corresponding increase in the
      unsaturated components. This effect was not seen in the M phase.

PMID- 9168610
TI  - A 16 kDa protein family overexpressed by Streptococcus thermophilus PB18 in acid
      environments.
AB  - The one- and two-dimensional protein patterns of Streptococcus thermophilus PB18
      in the exponential and stationary phases of growth were analysed. One-dimensional
      SDS-PAGE showed that a 16 kDa protein was overexpressed in stationary phase as
      well as 2 h after an acid shock, and that it was not expressed when the bacteria
      reached the stationary phase in medium with limiting lactose concentrations (5 or
      10 g l-1), in which the pH (5.5) was not as acid as in control cultures (pH 4.7,
      lactose 20 g l-1). The results support the idea that this protein is expressed in
      response to the acidic environment and not in response to the growth phase. Two
      dimensional PAGE showed that nine proteins were expressed only during the
      exponential phase and ten others only during the stationary phase. The 16 kDa
      band seen in one-dimensional SDS-PAGE corresponded to a 16 kDa protein family
      observed on two-dimensional SDS-PAGE/IEF gels, whose expression was increased 8.5
      fold when the extracellular pH reached a critical value below 5.0. The N-terminal
      sequences of proteins from two spots on the two-dimensional gels (members of the
      16 kDa family) were determined and found to be identical. The physiological role
      of this protein family has not yet been elucidated.

PMID- 9168611
TI  - Catabolism of D-glucose by Pseudomonas putida U occurs via extracellular
      transformation into D-gluconic acid and induction of a specific gluconate
      transport system.
AB  - Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway
      but requires (i) its oxidation to D-gluconic acid by a peripherally located
      constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii)
      accumulation of D-gluconic acid in the extracellular medium, and (iii) the
      induction of a specific energy-dependent transport system responsible for the
      uptake of D-gluconic acid. This uptake system showed maximal rates of transport
      at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these
      conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a
      different transport system, specific for the uptake of glucose, was also
      identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM
      potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

PMID- 9168612
TI  - Increased pyruvate orthophosphate dikinase activity results in an alternative
      gluconeogenic pathway in Rhizobium (Sinorhizobium) meliloti.
AB  - The formation of phosphoenolpyruvate (PEP) is a major step in the gluconeogenic
      pathway in which tricarboxylic acid (TCA) cycle intermediates are converted to
      hexose sugars. In Rhizobium (now Sinorhizobium) meliloti this step is catalysed
      by the enzyme PEP carboxykinase (PCK) which converts oxaloacetate to PEP. R.
      meliloti Pck- mutants grow very poorly with TCA cycle intermediates as the sole
      source of carbon. Here, the isolation and mapping of suppressor mutations which
      allow Pck- mutants to grow on succinate and other TCA cycle intermediates is
      reported. Tn5 insertions which abolished the suppressor phenotype and mapped to
      the suppressor locus were located within the pod gene encoding pyruvate
      orthophosphate dikinase (PPDK). Strains carrying suppressor mutations had
      increased PPDK activity compared to the wild-type. The suppressor phenotype was
      dependent on the combined activities of malic enzyme and PPDK, which thus
      represent an alternative route for the formation of PEP in R. meliloti. PPDK
      activity was not required for symbiotic N2 fixation.

PMID- 9168613
TI  - Mitochondrial superoxide dismutase is essential for ethanol tolerance of
      Saccharomyces cerevisiae in the post-diauxic phase.
AB  - This work reports the role of both superoxide dismutases-CuZnSOD (encoded by
      SOD1) and MnSOD (encoded by SOD2)-in the build-up of tolerance to ethanol during
      growth of Saccharomyces cerevisiae from exponential to post-diauxic phase. Both
      enzyme activities increase from the exponential phase to the diauxic shift and
      from the diauxic shift to the post-diauxic phase. The levels of mRNA-SOD1 and
      mRNA-SOD2 increase from the exponential phase to the diauxic shift; however,
      during the post-diauxic phase mRNA-SOD1 levels decrease while mRNA-SOD2 levels
      remain unchanged. These data indicate the existence of two regulatory mechanisms
      involved in the induction of SOD activity during growth: synthesis de novo of the
      proteins (until the diauxic shift), and post-transcriptional or post
      translational regulation (during the post-diauxic phase). Ethanol does not alter
      the activities of either enzyme in cells from the diauxic shift or post-diauxic
      phases, although the respective mRNA levels decrease in post-diauxic-phase cells
      treated with ethanol (14% or 20%). Results of experiments with sod1 and sod2
      mutants show that MnSOD, but not CuZnSOD, is essential for ethanol tolerance of
      diauxic-shift and post-diauxic-phase cells. Evidence that ethanol toxicity is
      correlated with the production of reactive oxygen species in the mitochondria is
      obtained from results with respiration-deficient mutants. In these cells, the
      induction of superoxide dismutase activity by ethanol is low; also, the
      respiratory deficiency restores the capacity of sod2 cells to acquire ethanol
      tolerance.

PMID- 9168614
TI  - Cloning of a protopectinase gene of Trichosporon penicillatum and its expression
      in Saccharomyces cerevisiae.
AB  - A protopectinase (PPase)-encoding gene, PSE3, from Trichosporon penicillatum was
      cloned by colony hybridization using two oligonucleotide probes synthesized from
      the N-terminal amino acid sequences of native PPase SE1 and one peptide from a
      lysyl endopeptidase digest. Nucleotide sequencing revealed that PSE3 contains an
      ORF encoding a 367 amino acid protein. Mature PPase SE3 is composed of 340 amino
      acids and the N-terminus of the ORF appeared to correspond to a signal peptide
      and a propeptide processed by a KEX2-like proteinase. The deduced amino acid
      sequence of PSE3 was 65.4, 56.7, 58.1, 61.8 and 48.9% homologous to the
      polygalacturonases of Aspergillus oryzae, Aspergillus niger, Aspergillus
      tubigensis, Cochliobolus carbonum and Fusarium moniliforme, respectively. One
      domain, which might interact with polygalacturonic acid, is highly conserved not
      only in fungal polygalacturonases but also in bacterial and plant
      polygalacturonases. PSE3 was expressed in Saccharomyces cerevisiae, but three
      forms (the mature form, a glycosylated form and an uncharacterized processed
      form) of PPase SE3 were present among the PSE3 products.

PMID- 9168615
TI  - Near-UV-induced absorbance change and photochemical decomposition of ergosterol
      in the plasma membrane of the yeast Saccharomyces cerevisiae.
AB  - When cells of the yeast Saccharomyces cerevisiae were exposed to near-UV (300-400
      nm), their absorption spectra changed slightly within the range 220-300 nm with
      increasing dosage. Difference spectra, calculated by substracting the curve
      recorded in cells exposed to near-UV from the curve of unexposed cells, decreased
      with increasing dosage over a broad band with peaks at 272, 282 and 295 nm and a
      shoulder at 265 nm. These peaks were in agreement with the absorption maxima of
      ergosterol, which is one of the major components of the plasma membrane of yeast.
      Near-UV radiation induced a simultaneous decrease in absorption spectra and
      reduction of ergosterol content in the plasma membrane. Photochemical
      decomposition of ergosterol by near-UV radiation was revealed in vivo, although
      ergosterol is generally known to be photoconverted to previtamin D2 industrially
      by UV radiation in vitro. In order to remove photosensitizers, liposomes were
      prepared from phospholipids and glycolipids, with or without ergosterol from
      purified yeast plasma membranes. Liposomal ergosterol in the orientated state was
      photochemically decomposed by near-UV radiation but ergosterol in the
      disorientated state in a homogeneous solution was not. Near-UV radiation also
      induced a decrease in activity of membrane-bound ATPase. Dose-response curves for
      the reduction of ATPase activity were similar to that for decomposition of
      ergosterol, suggesting that near-UV caused membrane function damage.

PMID- 9168616
TI  - beta-Glucosylated proteins in the cell wall of the black yeast Exophiala
      (Wangiella) dermatitidis.
AB  - Wild-type cells of the pathogenic black yeast Exophiala (Wangiella) dermatitidis
      grown in a low-pH ascorbate medium became less melanized and less resistant to
      Zymolyase. This was accompanied by increased staining with fluorescently labelled
      concanavalin A. The sugar composition of wild-type and mutant cell walls was,
      except for the presence of galactose, similar to that of Saccharomyces
      cerevisiae. Digestion of mutant cell walls with laminarinase released
      galactomannoproteins. In addition, the released cell wall proteins contained
      glucose and reacted with affinity-purified 1,6-beta-glucan antiserum, indicating
      that they are linked to 1,6-beta-glucan. It is proposed that 1,6-beta
      glucosylated cell wall proteins generally occur among ascomycetes.

PMID- 9168617
TI  - The flgK motility operon of Borrelia burgdorferi is initiated by a sigma 70-like
      promoter.
AB  - A cluster of flagellar genes of Borrelia burgdorferi was identified and
      sequenced. This cluster comprises an operon, designated the flgK operon, which is
      initiated by a sigma 70-like promoter. The flgK operon consists of flbF (function
      unknown), flgK (encoding HAP1), flgL (encoding HAP3) and orfX (function unknown),
      and maps at 185 kb on the chromosome. In other bacteria, the hook-associated
      proteins HAP1 and HAP3 connect the flagellar filament to the hook and are
      required for the last stage of flagellar assembly. Reverse transcriptase-PCR
      analysis indicated that flbF through to orfX are transcribed as a single mRNA,
      and primer extension analysis revealed that transcription of the flgK operon is
      initiated by a sigma 70-like promoter upstream of flbF. Subcloning the flgK
      promoter element into a promoter probe cat vector revealed that the flgK promoter
      element had strong activity in both Escherichia coli and Salmonella typhimurium.
      In addition, when this construct was transformed into a fliA mutant of S.
      typhimurium which lacked a functional flagellar-specific sigma 28 factor, the
      flgK promoter was still functional. Based on these results, the promoter element
      of the flagellin gene (fla, hereafter referred to as flaB) was re-examined. flaB
      encodes the flagellar filament protein, and a sigma gp33-34-like promoter has
      been reported to be involved in the transcription of this gene. A transcriptional
      start point was found 1 bp downstream of the reported start site. The sequence
      around -10 and -35 are consistent with the presence of a sigma 70-like promoter
      in addition to the putative sigma gp33-34-like promoter for flaB. In contrast to
      the flgK promoter element, no activity was detected after subcloning a flaB
      promoter element into the promoter probe cat vector. Because a sigma 70-like
      promoter rather than a unique flagellar sigma factor is involved in the later
      stage of flagellar assembly, the regulation of B. burgdorferi flagellar genes is
      evidently different from that of other bacteria.

PMID- 9168618
TI  - Analysis of a new dimeric extradiol dioxygenase from a naphthalenesulfonate
      degrading sphingomonad.
AB  - A new extradiol dioxygenase was cloned by screening a gene bank from the
      naphthalenesulfonate-degrading bacterial strain BN6 for colonies with 2,3
      dihydroxybiphenyl dioxygenase (DHBPDO) activity. A 1.6 kb DNA fragment was
      sequenced and an ORF of 954 bp identified. Comparison of the deduced amino acid
      sequence of DHBPDO II from strain BN6 with previously published sequences showed
      the closest relationship to a metapyrocatechase (MpcII) from Alcaligenes
      eutrophus JMP 222. Thus, the enzyme was only distantly related to the main groups
      of catechol 2,3-dioxygenases or DHBPDOs. The dioxygenase was expressed using a T7
      expression vector and the enzymic characteristics of the protein were examined.
      The enzyme oxidized 2,3-dihydroxybiphenyl, 3-isopropylcatechol, 3-methylcatechol,
      4-fluorocatechol and 1,2-dihydroxynaphthalene. Comparison of the UV/visible
      spectrum of the product formed from 3,5-dichlorocatechol with previous reports
      suggested that this substrate is oxidized by different extradiol dioxygenases
      either by proximal or distal ring cleavage. The enzyme required Fe2+ for maximal
      activity. In contrast to most other extradiol dioxygenases, the enzyme consisted
      of only two identical subunits.

PMID- 9168619
TI  - Highly thermostable endo-1,3-beta-glucanase (laminarinase) LamA from Thermotoga
      neapolitana: nucleotide sequence of the gene and characterization of the
      recombinant gene product.
AB  - The nucleotide sequence of clone pTT26 (3786 bp), containing the gene for 1,3
      beta-glucanase LamA (laminarinase) from Thermotoga neapolitana, was determined.
      It contains an ORF encoding a protein of 646 aa (73328 Da). The central part of
      the protein is homologous to the complete catalytic domain of bacterial and some
      eukaryotic endo-1,3-beta-D-glucanases and belongs to family 16 of glycosyl
      hydrolases. This domain is flanked on both sides by one copy on each side of a
      substrate binding domain homologue (family II). The recombinant laminarinase
      protein was purified from Escherichia coli host cells in two forms, a 73 kDa and
      a processed 52 kDa protein, both having high specific activity towards laminarin
      (3100 and 2600 U mg-1, respectively) and K(m) values of 2.8 and 2.2 mg ml-1,
      respectively. Limited activity on 1,3-1,4-beta-glucan (lichenan) was detected (90
      U mg-1). Laminarin was degraded in an endoglucanase modus, yielding glucose,
      laminaribiose and -triose as end products. Thus LamA classifies as an endo-1,3(4)
      beta-glucanase (EC 3.2.1.6). The optimum temperature of the enzymes was 95
      degrees C (73 kDa) and 85 degrees C (52 kDa) at an optimum pH of 6.2. The
      superior thermostability of the 73 kDa enzyme is demonstrated by incubation
      without substrate at 100 degrees C, where 57% of the initial activity remained
      after 30 min (82% at 95 degrees C). Thus, LamA is the most thermostable 1,3-beta
      glucanase described to date.

PMID- 9168620
TI  - Molecular and immunological characterization of OprL, the 18 kDa outer-membrane
      peptidoglycan-associated lipoprotein (PAL) of Pseudomonas aeruginosa.
AB  - Immunological screening of a Pseudomonas aeruginosa cosmid library led to the
      identification of clones producing an 18 kDa outer-membrane protein. This protein
      reacted in Western blots with a polyclonal antiserum against outer-membrane
      proteins of P. aeruginosa and with a monoclonal antibody (MA1-6) specific for
      OprL, the peptidoglycan-associated outer-membrane lipoprotein (PAL). Sequencing
      of pOML7, a subclone expressing oprL, revealed an ORF of 504 bp encoding a
      polypeptide with a typical lipoprotein signal recognition sequence. Another ORF
      was found upstream of oprL, with homology to the TolB protein of Escherichia coli
      and Haemophilus influenzae. Downstream of oprL, a second ORF, of 321 bp, was
      found (orf2), encoding a protein with a signal peptide and with no homology with
      proteins of known biological function. After the stop codon of orf2, a rho
      independent terminator sequence was detected which is part of the P. aeruginosa
      PAO1 insertion element IS222. OprL showed homologies with all known PALs from
      Gram-negative bacteria, especially in the C-terminal part. mAb MA1-6 reacted with
      P. aeruginosa cells in immunofluorescence, and with E. coli cells expressing
      oprL, which had an abnormal, elongated morphology, an indication that production
      of the protein perturbed the division process.

PMID- 9168621
TI  - Fluorescent oligonucleotide rDNA probes that specifically bind to a common
      nanoflagellate, Paraphysomonas vestita.
AB  - Nanoflagellates are ecologically important, but morphological identification
      requires techniques which are not practicable for use in quantitative studies of
      populations; alternative methods of accurate recognition of nanoflagellate
      species in mixed populations are therefore desirable. Fluorescent oligonucleotide
      probes which hybridize with unique sequences of the small subunit (SSU) rRNA have
      been exploited as 'phylogenetic stains' in the identification of bacteria. In
      this paper we describe the preparation and application of probes which
      specifically hybridize with a common nanoflagellate species, Paraphysomonas
      vestita. The sequence of nucleotides in the SSU rRNA gene of this flagellate was
      determined and compared with those of related species to select unique P. vestita
      sequences 18-21 nucleotides in length. Five sequences in different parts of the
      SSU rRNA gene were used to design 5'-fluorescently labelled oligonucleotide
      probes. Published sequences were used to make probes that hybridized with all
      eukaryotes (EUK) or any cellular organism (UNI), and probes were designed not to
      hybridize with rRNA (CON). Optimum conditions for hybridization were determined.
      In all cases, UNI probes hybridized with the cells, but CON probes were only
      bound to a limited extent. All five probes targeted to P. vestita proved to be
      species-specific; they hybridized well with this species, but not with three
      other species of the same genus, nor with three more distantly related flagellate
      species, nor with a ciliate, nor with bacteria. These probes provide a means of
      quantitatively measuring the proportion of P. vestita cells in samples of mixed
      protists.

PMID- 9168622
TI  - Molecular and mutational analysis of a DNA region separating two methylotrophy
      gene clusters in Methylobacterium extorquens AM1.
AB  - A region of 14.2 kb has been analysed that is a part of a locus on the
      Methylobacterium extorquens AM1 chromosome containing a number of genes involved
      in one-carbon (C1) metabolism, including serine cycle genes, pqq genes,
      regulatory methanol oxidation genes and the gene for N5,N10-methylene
      tetrahydrofolate dehydrogenase (mtdA). Fifteen new ORFs have been identified
      within the new region, and their sequences suggest that they encode the following
      polypeptides: the C-terminal part of phosphoenolpyruvate carboxylase, malyl-CoA
      lyase, polypeptides of 9.4 and 31 kDa of unknown function, three putative
      subunits of an ABC-type transporter, two polypeptides similar to the products of
      mxaF and mxaJ from M. extorquens AM1 and other methylotrophs, a cytochrome c,
      three enzymes of folate metabolism, and polypeptides of 13 and 20.5 kDa with no
      homologues in the protein database. Ten insertion mutations have been generated
      in the region to determine if the newly identified genes are associated with C1
      metabolism. A mutation in mclA, encoding malyl-CoA lyase, resulted in a C1-minus
      phenotype, while mutations in the other genes all showed a C1-plus phenotype. It
      was not possible to obtain null mutants in a putative folate metabolism gene,
      folC, implying the necessity of these folate synthesis genes for metabolism of C1
      and multicarbon compounds. Mutations in the putative ABC transporter genes, the
      genes similar to mxaG and mxaJ, and other unidentified ORFs produced double
      crossover recombinants with a C1-positive phenotype. Promoter regions have been
      investigated upstream of orf3 and orf4 using the promoter probe vector pHX200.
      Transcription from these promoters was weak in wild-type M. extorquens AM1 but
      increased in regulatory mox mutants.

PMID- 9168623
TI  - Molecular analysis of mxbD and mxbM, a putative sensor-regulator pair required
      for oxidation of methanol in Methylobacterium extorquens AM1.
AB  - Five genes are thought to be required for transcription of methanol oxidation
      genes in Methylobacterium strains. These putative regulatory genes include mxcQE,
      which encode a putative sensor-regulator pair, and mxbDM and mxaB, whose
      functions are less well-understood. In this study, mxbDM in Methylobacterium
      extorquens AM1 were shown to be required for expression of a xylE transcriptional
      fusion to the structural gene for the large subunit of methanol dehydrogenase
      (mxaF), confirming the role of these genes in transcriptional regulation of mxaF.
      The nucleotide sequence suggests that mxbD encodes a histidine protein kinase
      with two transmembrane domains and that mxbM encodes a DNA-binding response
      regulator. A xylE transcriptional fusion to the putative mxbD promoter showed low
      level expression in wild-type cells grown on one-carbon (C1) compounds and no
      detectable expression in cells grown on succinate. Deletion analysis of this
      promoter construct showed that the region 229-129 bp upstream of the start of
      mxbD is required for expression. The expression of the mxbD-xylE fusion was
      examined in each of the five known regulatory mutant classes. xylE expression was
      reduced to non-detectable levels in MxcQ and MxcE mutants, but was not affected
      in the other regulatory mutants or in non-regulatory mutants defective in
      methanol oxidation. These results suggest a regulatory hierarchy in which the
      sensor-regulator pair MxcQE control expression of the sensor-regulator pair
      MxbDM, and MxbDM in turn control expression of a number of genes involved in
      methanol oxidation.

PMID- 9168624
TI  - Propionibacterium acnes, a resident of lipid-rich human skin, produces a 33 kDa
      extracellular lipase encoded by gehA.
AB  - Five independent clones of the Propionibacterium acnes P-37 lipase gene (gehA)
      were obtained in Escherichia coli, and the gene was localized to a 2.75 kb Xhol
      fragment by subcloning. The five clones were shown to contain the same gene by
      Southern blotting with a DIG-labelled probe to gehA. The nucleotide sequence of
      gehA was determined, and shown to contain a single ORF of 1017 kb, encoding a
      protein of 339 amino acids. The predicted molecular mass was 36 kDa. A 33 kDa
      (PAGE) radiolabelled polypeptide was detected from E. coli minicell preparations
      harbouring gehA, which could correspond to GehA after cleavage of the putative 26
      amino acid residue signal peptide. gehA was overexpressed in E. coli under the
      control of the bacteriophage T7 promoter, and the corresponding polypeptide was
      found to be present in insoluble aggregates. Active lipase was produced when the
      overexpressing strain was incubated at a reduced temperature in the presence of
      sucrose. Purification of lipase from P. acnes culture supernatant fluids
      confirmed the production of a 33 kDa (PAGE) lipase.

PMID- 9168625
TI  - Control of Neisseria gonorrhoeae pilin gene expression by environmental factors:
      involvement of the pilA/pilB regulatory genes.
AB  - The control of the expression of the pilin gene (pilE) in Neisseria gonorrhoeae
      under a wide variety of growth conditions has been studied. The expression of
      pilE was measured using transcriptional fusions between pilE and the gene
      encoding chloramphenicol acetyltransferase (CAT), and the level of pilin
      production was measured by Western blot analysis. Many of the conditions tested
      affected both growth rate and pilin gene expression (e.g. isoleucine, high
      osmolarity, high temperature, anaerobic growth, pH 6, urea and iron depletion).
      Changes in the level of many other proteins were also observed, depending on the
      conditions, indicating that gonococci undergo an adaptive response to
      environmental variations. Moreover, environment-induced changes in the level of
      many proteins, including pilin, seem to involve the pilA/pilB regulatory system,
      which has been previously proposed to modulate the expression of the gonococcal
      pilin gene.

PMID- 9168626
TI  - Variation in assimilating functions occurs in spontaneous Candida albicans
      mutants having chromosomal alterations.
AB  - In this study, four clinical isolates and over 100 colony morphology mutants,
      previously derived spontaneously from strain 3153A during growth on glucose
      medium, were examined for their utilization of 21 carbon and 3 nitrogen sources
      at various growth temperatures. The results demonstrated extensive variability in
      the pattern of assimilation among the mutants and strains, including both the
      gain and loss of assimilating functions. The persistent alterations in
      assimilation patterns observed in sequentially produced subclones illustrated an
      extensive ability of C. albicans populations to constantly produce new
      combinations of assimilating functions. The variability among spontaneous mutants
      derived from a single strain explains the well documented variability among
      natural isolates. From these results we established a relationship between the
      previously documented broad spectrum of spontaneous chromosomal aberrations in
      these mutants to the expression of genes controlling the utilization of
      alternative carbon and nitrogen sources. The existence of cryptic genes,
      responsible for growth on alternative substrates, was previously deduced from the
      analysis of other mutants obtained as a response to the restrictive condition on
      media containing non-assimilating carbon sources. Thus, mutants with altered
      assimilation functions can arise either on glucose medium or by selection on
      restricted media. Extensive differences between the patterns of chromosomal
      aberrations and the distribution of correlated phenotypes in the two groups of
      mutants indicated that the same phenotypes may be produced by two different
      mechanisms involving the same or different genes.

PMID- 9168627
TI  - Bacteriocins: nature, function and structure.
AB  - Bacteriocins are extracellular substances produced by different types of
      bacteria, including both Gram positive and Gram negative species. They can be
      produced spontaneously or induced by certain chemicals such as mitomycin C. They
      are biologically one of the important substances, and have been found to be
      useful in membrane studies and also in typing pathogenic microorganisms causing
      serious nosocomial infections. Bacteriocins are a heterogeneous group of
      particles with different morphological and biochemical entities. They range from
      a simple protein to a high molecular weight complex: the active moiety of each
      molecule in all cases seems to be protein in nature. The genetic determinants of
      most of the bacteriocins are located on the plasmids, apart from few which are
      chromosomally encoded. These bactericidal particles are species specific. They
      exert their lethal activity through adsorption to specific receptors located on
      the external surface of sensitive bacteria, followed by metabolic, biological and
      morphological changes resulting in the killing of such bacteria. This review
      summarises the classification, biochemical nature, morphology and mode of action
      of bacteriocins as well as their genetic determinants and the microbiological
      relevance of these bactericidal agents.

PMID- 9168628
TI  - Trends in the utilization of blood components in San Pablo Hospital; 1991-1996.
AB  - OBJECTIVE: The purpose of this paper was to evaluate the trends in the use of
      blood products in our hospital during the last six years. We selected for the
      study packed red cells and platelet products since they are the most frequently
      used, on a unit per unit basis they represent a larger component of the
      transfusion service budget and finally are the most frequent units involved in
      transfusion reactions. METHODS: The variables in the data bank that were utilized
      to study included, patients transfused, patients operated, units transfused,
      units prepared, and units discarded. From these variables we constructed the
      following new variables, Cross match to Transfusion ratio, units transfused to
      patients transfused ratio, units transfused to patients operated ratio, and
      finally patients operated to patients transfused ratio. The data was then
      organized by year and transported to SPSS software where the null hypothesis was
      tested through an analysis of the variance (ANOVA). RESULTS: The number of
      patients who underwent coronary artery bypass surgery increased over the last six
      years. An average increase of six additional patients per month was documented.
      An increase in the total number of packed Red Cells units transfused was seen
      with a mean of 167 units per month in 1992, 182 units in 1994 and 187 units in
      1996. (p = .425). A mean of 45 patients per month were transfused in 1992 as
      compared to 55 and 56 in 1994 and 1996 respectively. (p = .009). The ratio of
      patients operated to patients transfused decreased from 1.65 in 1992 to 1.3 and
      1.4 in 1992 and 1996. (p = .021) The intensity of Red Cell use in patients
      undergoing surgery was analyzed by using the ratio of number of red cell units
      transfused by the number of patients operated and transfused. This ratio was 3.7
      in 1992, 3.2 in 1994 and 3.3 in 1996. (p = .032) The use of platelets transfusion
      in the cardiovascular surgery arena appears to have changed very slightly over
      the five years in our institution. A non-significant trend in the number of
      patients who are operated and are transfused with platelets is noted, along with
      a mild decrease in the intensity of platelet use per patient transfused. NON
      CARDIOVASCULAR SERVICE: The number of patients transfused with packed Red Cells
      has not changed significantly in this service since 1992. The mean number of
      units transfused per month in 1992 and in 1994 was close to 222. In 1996, a mean
      number of 230 units per month were transfused. (p = .172) The mean number of
      patients transfused increased slightly from 74.5 patients per month in 1992 to
      77.5 in 1994 and 77.7 in 1996. (p = .585) The intensity of Red Cell transfusion
      support decreased somewhat with 2.98 in 1992 to 2.87 and 2.95 in 1994 and 1996.
      (p = .806) A marked increase in the number of platelet transfusion was
      documented. A mean number of 192 units were transfused in 1992 per month as
      compared to 333 and 360 in 1994 and 1996. (p = .27) This increase in platelet use
      was associated to an increase in the number of patients who were transfused with
      9 per month in 1992 and 16.5 and 16.4 in 1994 and 1996. (p = .005) The mean
      number of platelet transfused per patient decreased in a non significant fashion
      with 19.9 units and 20.6 units per transfused patient in 1992 and in 1994 to 19.2
      units in 1996. (p = .861). CONCLUSION: We have been able to define distinct
      changes in the trends of blood product utilization in our institution.

PMID- 9168629
TI  - Laparoscopic cholecystectomy in pregnancy.
AB  - Several recent literature reviews have shown that Laparoscopic cholecystectomy
      can be performed safely in pregnant females with symptomatic gallbladder disease.
      We have performed a retrospective analysis of all patients who underwent a
      cholecystectomy (6,080 patients) from January 1, 1990 until December 31, 1996 at
      San Pablo Medical Center. Lapa-cholecystecomy was performed in 4,252 (64%) and in
      the remaining 1,828 (36%) patients, an open cholecystectomy performed. Of the
      Laparoscopic cases, 5(0.1%) were performed in pregnant females with complicated
      gallbladder disease(GBD). The diagnosis of GBD was done with an abdominal
      sonogram. Four of the 5 patients had suffered from gallstones pancreatitis and
      one acute cholecystitis, prior to the operation. The records of patients were
      reviewed to secure the following variables, age, pre and post operative course
      and outcome. Intraoperative cholangiogram performed in 1 patient. No
      complications were seen in the mother or in the fetus in any of the five cases.
      Literature was reviewed to assess our reports. CONCLUSIONS: Pregnant females with
      complicated gallbladder disease can be safely managed with Laparoscopic
      cholecystectomy.

PMID- 9168630
TI  - A survey of parental knowledge about car seats in children.
AB  - Motor vehicle accidents are the main cause of death and disability between 1 and
      4 years of age. Since 1980 the Academy of Pediatrics has been promoting the
      correct use of car seats. The major reason that car seats are not fulfilling
      their full potential is their incorrect or lack of use. In order to evaluate
      parental knowledge about car seat use for children and their actual use in the
      population visiting HURRA, a survey was performed which demonstrated that only
      57.6% of the parents interviewed had infant car seats and that only 83.3% of
      owners actually use it. As many as 94.4% had correct knowledge about car seat
      use, but the majority of correct information was not provided by the medical
      staff. The majority of parents use seat belts for their own protection but a
      significantly smaller percentage use car seats for their own children.

PMID- 9168631
TI  - Impact of thrombolytic therapy for myocardial infarction in the Bayamon Public
      Health Care Sector--1993-1995 experience.
AB  - The study was designed to evaluate the compliance of general management
      guidelines, determine the effectiveness of Thrombolytic therapy (TTX), determine
      the complications, statistics and the "Door to Needle" time (DTN) in the
      management of Myocardial Infarction (MI) in the Bayamon public health care
      sector. METHODS: Retrospective record review and SPSS statistical calculations
      were performed. RESULTS: 66 cases (49m, 17f) discharged with MI from January 1993
      to June 1995 were included. 27 received TTX. 80% were between 30-69 y/o, while
      20% from 70-87 y/o. Past hx and habits; smoker 62%, ETOH 45%. Labs in adm; hypoMG
      15%, hypoK 11%. The Q MI = 63%, Non Q = 38%. The sinoatrial and ventricular
      arrhythmias were seldom seen (7.5% SVT, AIVR 3%). Intra and atrioventricular
      block (3%). The most frequent cardiac complication was CHF 10% and the non
      cardiac; BKP 16.5%. The mortality was (6.1%). The mean stay was 9.34 days.
      Therapy used; IV NTG 97%, ASA 84%, beta B 39%, TTX 42.2%, ACE inhibitors 32%.
      Absence of TTX was usually due to absence of EKG criteria (63%). TTX
      complications; hypotension 10.5%. The mean DTN was 1hr 58m,. 91% were discharged
      home, 23.3% cath, deaths 6%. The ER MD assessment of MI was correct in only 29%.
      CONCLUSIONS: The complications of patients with MI in the TTX era are below the
      ones before TTX. Mortality and morbidity have improved with the use of TTX. The
      medical therapy guidelines of MI are generally followed in HURRA. Improvement in
      the DTN is needed. The prolonged DTN and the inconsistency of the admission
      assessment by the ER personnel establishes the need to develop a training program
      which would regulate this abnormality.

PMID- 9168632
TI  - Evolving trends in thyroid surgery at San Pablo Hospital and Medical Center.

PMID- 9168633
TI  - Impact of minimally invasive surgery in children.
AB  - An important medical technological progress of this century corresponds to the
      application of minimal invasive surgical techniques in adults and children.
      Laparoscopic surgery is causing an impact in the results of many procedures done
      during the pediatric age. Within this review we explore the development of
      laparoscopic abdominal surgery in children along with basic physiology and
      complications of establishing a potential working space (pneumoperitoneum).
      Indications, results, and where we are headed in the management of various of the
      most common surgical conditions of children are issues discussed. Laparoscopic
      surgery has proven safe, efficient, technically feasible and well tolerated in
      most children. Produces early return to activities, reduced hospital stay, less
      hospital bills, and better cosmetic results when compared to open (conventional)
      procedures.

PMID- 9168634
TI  - Septicemia due to a non-0:1, non-0:139 Vibrio cholerae.
AB  - We describe a patient with a non-0:1, non-0:139 Vibrio cholerae septicemia
      associated with ecythema gangrenosa-like skin lesions. The patient acquired the
      infection in Puerto Rico. Given the high fatality rate, it is important for the
      medical community to consider the diagnosis in high risk patients with exposures
      in Puerto Rico tropical waters.

PMID- 9168635
TI  - Introduction to economic credentialing.

PMID- 9168636
TI  - [Potentiating effect of ethanol on alpha 1 adrenergic receptor mediated
      contraction of thoracic aorta from guinea pig].
AB  - Using aortic strips isolated from guinea pigs, effects of ethanol on vascular
      smooth muscle tonus were studied. 50mM of ethanol significantly potentiated the
      contractions induced by norepinephrine and phenylephrine, but did not influence
      those induced by KCl and clonidine. Furthermore, ethanol significantly augmented
      the contraction induced by phenylephrine in the presence of verapamil, and did
      not have any effects on the contractions induced by A23187, Ba2+, PDBu and BAY K
      8644. These results indicate that ethanol potentiates the alpha 1 adrenergic
      receptor-mediated contraction, depending on the extracellular calcium influx via
      the receptor-operated calcium channel.

PMID- 9168637
TI  - [Histopathological study on acute poisoning of methamphetamine, morphine or
      cocaine].
AB  - Methamphetamine, morphine or cocaine was injected intraperitoneally into Wistar
      rats (male, 6 weeks old) at a dose of 50 mg/kg, 125 mg/kg, or 50 mg/kg body
      weight, respectively. These doses of drugs were determined to ensure that the
      rats would show signs of drug intoxication and survive for a day. Over the period
      from 5 min to 18 hr after injection, concentrations of the drugs and metabolites
      in blood were analyzed by the GC/MS method, and the histopathological changes of
      the heart, lungs, liver and kidneys were examined by light microscopy. The time
      of maximum drug concentration in the blood after injection was 5 min in the
      methamphetamine-treated group, 1 hr (total morphine) in the morphine group and 5
      min in the cocaine group. These blood concentrations decreased with time. In the
      liver at 2.5 hr after injection of methamphetamine, centrolobular vacuolation and
      diffuse eosinophilic changes of hepatocytes appeared. At 6 hr this damage spread
      to the midzone of the liver and partial necrosis of the centrolobe was found. At
      18 hr the liver damage became worse and necrosis was also found in the midzone of
      the liver. In the heart, from 2.5 hr, eosinophilic changes of the myocardium were
      observed diffusely. Furthermore, at 18 hr, partial inflammatory cell infiltration
      and contraction bands were observed. The degree of histopathological damage did
      not coincide with the time of maximum drug concentration. In the morphine group,
      centrolobular and midzonal vacuolation, diffuse fatty degeneration and
      eosinophilic changes were observed in the liver from 2.5 hr to 18 hr after the
      administration. No necrosis was found, perhaps because the rats did not suffer
      the hyperthermia observed in the methamphetamine group. The degree of
      histopathological damage became more serious with time, as it did in the
      methamphetamine group. In the cocaine group, no histopathological changes were
      observed, probably because the doses of cocaine were too small to cause
      histopathological damage, and because cocaine is more rapidly metabolized than
      methamphetamine or morphine. These results suggest that in histopathological
      investigations necessitated by drug intoxication, measuring drug concentrations
      in the blood might be useful in determining the causes of histopathological
      changes more clearly.

PMID- 9168638
TI  - Effects of ethanol on the levels of brain 6R-L-erythro-5, 6, 7, 8
      tetrahydrobiopterin in the inbred strains of mice. DBA/2J, C3H/HeJ and C57BL/6J
      with different alcohol preferences.
AB  - 6R-L-erythro-5, 6, 7, 8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine,
      tryptophan and phenylalanine hydroxylases, the former two of which are the
      initial and the rate-limiting enzymes in the biosynthesis of the catecholamines
      and serotonin, respectively. The present study was designed to determine the
      changes in concentrations of 6R-BH4 in striatum and midbrain of the inbred
      strains of mice, DBA/2J, C3H/HeJ and C57BL/6J, with different genetically
      determined alcohol preferences, following the injection of ethanol (EtOH). The
      intraperitoneal administration of EtOH (0, 1, 2 and 4 g/kg) significantly and
      dose-dependently reduced the levels of striatal and midbrain 6R-BH4 in DBA/2J
      mice with the lowest alcohol preference, and EtOH (4 g/kg, i.p.) reduced the
      level of striatal 6R-BH4 in C3H/HeJ with medium alcohol preference. Following the
      administration of EtOH (4 g/kg, i.p.), brain 6R-BH4 levels in C57BL/6J mice with
      high alcohol preference were lowered compared with the control group, but the
      difference did not reach statistic significance. EtOH has a tendency to reduce
      the brain 6R-BH4 levels in mice with lower alcohol preference or higher
      sensitivity to EtOH. Based on these findings, it was proposed that differences in
      alcohol drinking behavior in the inbred strains of mice was influenced by brain
      6R-BH4.

PMID- 9168639
TI  - [Evaluation of intrapulmonary nodules by thoracoscopic ultrasonography].
AB  - We evaluated the usefulness of thoracoscopic ultrasonography for diagnosing
      intrapulmonary nodules. We studied 7 patients undergoing thoracoscopic
      operations. Three had benign lung tumors, one had metastatic lung tumors from a
      renal cell cancer, and three had primary lung cancers. During thoracoscopy three
      benign tumors were seen as masses protruding from the visceral pleura in to the
      pleural space, and two primary lung cancers were seen as pleural indentations.
      However, the presence of one metastatic lung tumor and one primary lung cancer
      could not be confirmed by thoracoscopy because of the lack of pleural changes.
      Furthermore, intrapulmonary spread of malignant tumors in four cases could not be
      seen by thoracoscopy. All tumors were seen clearly and their characteristics were
      identified by thoracoscopic ultrasonography. Partial lung resection during
      thoracoscopy was successful in all patients. We found thoracoscopic
      ultrasonography to be useful for confirming the presence of peripheral solid
      nodules, and for deciding where to make incisions for partial lung resection.

PMID- 9168640
TI  - [Effect of percutaneous transluminal mitral commissurotomy on pulmonary function
      and on the pulmonary vasculature].
AB  - We evaluated the therapeutic effect of percutaneous transluminal mitral
      commissurotomy (PTMC) on pulmonary function, and the damage caused to pulmonary
      vasculature by transient occlusion of the mitral valve during PTMC in patients
      with mild mitral stenosis. Pulmonary function tests were done and serum
      thrombomodulin was measured in 6 patients before and after PTMC. The mean
      pulmonary arterial pressure and mean pulmonary arterial wedge pressure decreased
      significantly from the control values, and the decreases were proportional to the
      increase in the area of the mitral valve. VC, %VC, and DLco were in the normal
      range before and after PTMC but PEFR, FEV1%, FEV1, V50, V25, and V50/V25 were
      significantly higher after PTMC. Change in the area of the mitral valve
      correlated with the changes in FEV1% (r = 0.841), in V50 (r = 0.624), and in V25
      (r = 0.697). The serum thrombomodulin levels before and after PTMC did not
      differ. We conclude that pulmonary dysfunction in patients with mild mitral
      stenosis MS is mainly due to an obstructive ventilatory defect, and that PTMC can
      correct this dysfunction without damaging the pulmonary vasculature.

PMID- 9168641
TI  - [Tuberculosis in patients with human immunodeficiency virus infection].
AB  - Six men (mean age: 36.3 +/- 29 years) infected with the human immunodeficiency
      virus (HIV), four Japanese and two from Myammar, were admitted to our hospital
      for treatment of tuberculosis. In five, HIV positivity on serologic testing was
      first found when tuberculosis was diagnosed. The mean CD4 cell count was 37.3 +/-
      29.6/microliters. Results of tuberculin skin tests were negative in 5 patients.
      One patient had pulmonary tuberculosis and 5 had miliary tuberculosis. Hilar and
      mediastinal lymphadenopathy was found on chest X-ray films in 4 patients and
      superficial lymphadenopathy was found in all patients. All patients had positive
      mycobacterial cultures of sputum and 2 patients had positive tests for acid-fast
      bacilli on smears of lymph-node aspirates. In one patient with tuberculosis
      meningitis, a culture of cerebrospinal fluid for acid-fast bacilli was positive.
      Epithelioid cell granulomas were found in samples of lung, liver, and bone marrow
      from 4 patients. Mycobacterium tuberculosis was isolated from all patients, and
      was not resistant to isoniazid, rifampicin, ethambutol, or streptomycin.
      Therefore all patients responded well to treatment of tuberculosis.

PMID- 9168642
TI  - [Problems in noninvasive positive pressure ventilation of patients with acute-on
      chronic hypercapnic respiratory failure].
AB  - In patients with acute exacerbations of chronic obstructive pulmonary disease non
      invasive positive pressure ventilation (NPPV) has been used to avoid endotracheal
      intubation. The aim of this study was to identify factors that can prevent the
      success of this technique. We applied a BiPAP ventilatory assist device
      (Respironics, Inc., Murrysville, PA) via a nasal mask to 13 patients with acute
      exacerbation of chronic respiratory failure and analyzed their clinical and
      physiological status. Intubation was not needed in 11 of 14 episodes (78%). The
      mean pH, PaCO2, and heart rate before BiPAP in the three patients who required
      intubation differed significantly from those in the patients who did not require
      intubation (pH 7.19 vs. 7.31: p < 0.05, PaCO2 107.8 vs. 77.8 Torr: p < 0.05,
      heart rate 127 vs. 105/min; p < 0.05). In those who required intubation the mean
      pH improved during the first 12 hours of BiPAP but then worsened. In 5 episodes,
      the PaCO2 increased during the initial trial of BiPAP, but decreased after the
      amount of supplemental oxygen was reduced. We conclude that NPPV should be used
      soon after respiratory failure begins, and care should be taken not to supply too
      much oxygen.

PMID- 9168643
TI  - [Clinicopathological features of interstitial pneumonia associated with
      amyopathic dermatomyositis].
AB  - We studied clinicopathological characteristics of interstitial pneumonia
      associated with amyopathic dermatomyositis. The subjects comprised two men and
      three women, and their mean age was 58.2 years. All subjects had cruptions
      specific for dermatomyositis, but had no signs of myositis. They all presented
      with acutely or subacutely developed coughing and dyspnea. Results of tests for
      anti-Jo-1 antibody were negative in all cases. Chest X-ray films showed
      infiltrations or streaky shadows, or both in the middle and lower lung fields.
      Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of
      lymphocytes and neutrophils. In one patients a specimen obtained by open lung
      biopsy showed homogeneous cell infiltrations in alveolar septa and regional
      alveolar damage. That patient was successfully treated with cyclosporin and
      corticosteroids in early phase of the disease. The other four patients received
      immunosuppressive agents after respiratory failure developed. All four died
      despite having received high-dose corticosteroid and immunosuppressive therapy.
      Examination of autopsy specimens showed diffuse alveolar damage.

PMID- 9168644
TI  - [Effect of smoking on the decline in forced expiratory volume in one second].
AB  - We used multiple regression analysis to study the effects of smoking cessation on
      the decline in forced expiratory volume in one second (FEV1). We studied 429
      healthy men for about 3 years. Each subject was assigned to one of three groups,
      according to their self-reported smoking history: 281 were current smokers, 67
      were former smokers, and 81 had never smoked. After statistical adjustment for
      initial age, initial FEV1, and decline in Maximum Mid-expiratory Flow (MMF),
      current smoking was found to be associated with a faster decline in FEV1. Having
      stopped smoking was associated with a slower decline in FEV1. The rate of decline
      in MMF was associated with the rate of decline in FEV1, which suggests that the
      rate of decline in FEV1 was greater in those subjects with small airways disease.

PMID- 9168645
TI  - [Incidence and clinical features of lung cancer in patients with idiopathic
      interstitial pneumonia].
AB  - We studied the incidence of lung cancer in the 599 patients with idiopathic
      interstitial pneumonia (IIP) who had visited to 37 institutions during 1991. In
      addition to 89 patients with lung cancer registered initially 29 were found
      during more than 4 years of follow-up, which indicates that annual incidence of
      lung cancer in these patients with IIP was a few percent. A total of 118 lung
      cancers accounted for 19.7% of all the IIP patients registered and also for 27.2%
      of the 435 IIP patients in whom a definite outcome was certified by this study.
      Most of the patients with lung cancer were older men who were heavy smokers. The
      distribution of histological types was not noteworthy. On the chest rentgenogrms,
      the tumors were found predominantly in the peripheral lung fields even in the
      patients with squamous cell cancer, but no apparent association with IIP lesion
      was observed. Surgical resection was done in only 52% of the patients with the
      disease at stage I or II; chemotherapy and/or radiotherapy were given to 52.4% of
      the patients with advanced disease, which may have been due to considerations of
      the adverse effects of anticancer treatment on the prognoses. The mortality in
      IIP patients with lung cancer was higher than in those without lung cancer,
      mainly due to progression of the lung cancer, not the IIP. This indicates the
      importance of lung cancer as a prognostic factor in patients with IIP.

PMID- 9168646
TI  - [Usefulness of enhanced computed tomography in the diagnosis of pulmonary
      thromboembolism].
AB  - Pulmonary thromboembolism (PTE) was diagnosed in 22 patients at Saga Medical
      School between 1981 and 1994. Enhanced computed tomography (CT) was done in 8
      patients, and filling defects in the central pulmonary artery were identified in
      6. Parenchymal shadows (wedge shaped shadows, subpleural consolidation, or
      nodular shadow's) were noted in 5. When enhanced CT was done during acute severe
      respiratory failure in 3 patients, pulmonary artery filling defects were found in
      all. These findings suggest that enhanced CT is useful as a diagnostic tool for
      acute PTE with respiratory failure. Electron beam CT may be a sensitive and
      specific means of diagnosing PTE because it can be done quickly and without
      breath-holding. We conclude that enhanced CT should be used as the first
      diagnostic procedure in patients with severe respiratory failure who may have
      PTE.

PMID- 9168647
TI  - [Adenosquamous cell carcinoma of the lung with multiple cystic metastases in the
      liver].
AB  - A 70-year-old man was admitted to the hospital because of mild dyspnea, a cough,
      and hemoptysis. A chest X-ray film and a computed tomographic scan showed a mass
      in the S1.2 region of the left lung, and swollen mediastinal lymph noes.
      Cytologic examination of sputum sample resulted in the diagnosis of lung cancer.
      The tumor did not respond to chemotherapy, and the patient died after seven
      months. Autopsy disclosed a solid tumor of left lung and many cystic lesions in
      the liver. Histological examination of the lung lesion revealed adenosquamous
      cell carcinoma. Metastatic lesions in the liver consisted of adenosquamous cell
      carcinoma, with predominantly squamous cell carcinoma. Cases of lung cancer in
      which hepatic metastases have many cystic cavities are rare.

PMID- 9168648
TI  - [Three cases of malignant lymphoma that developed from the chest wall].
AB  - Chronic tuberculous pyothrax and the development of non-Hodgkin's lymphoma (NHL)
      on the chest wall are believed to be closely related. We encountered three
      patients with NHL involving the chest wall in whom the tumor may have had a
      different origin Patient 1: A 65-year-old man with a history of pulmonary
      tuberculosis and right-sided pyothrax at the age of 28 years was found to have a
      tumor on the right sided of the chest wall, and NHL was diagnosed. Patient 2: A
      65-year old woman with a history of right-sided tuberculous pyothrax at the age
      of 2 years had a left-sided chest-wall tumor, and NHL was diagnosed. Patient 3: A
      78-year-old man with a history of tuberclous pleuritis on the left side at the
      age of 77 years was found to have a left-sided chest-wall tumor, and NHL was
      diagnosed. In patients 1 and 2, the Epstein-Barr virus was found in tissue
      specimens by in situ hybridization. These findings suggest that chronic
      tuberculous pyothrax and the development of NHL on the chest wall were not
      closely related in these patients, and that the Epstein-Barr virus may play an
      important role in the development of NHL on the chest wall after tuberculous
      pyothrax.

PMID- 9168649
TI  - [Interstitial pneumonia with Sjogren's syndrome: successful treatment with
      steroids and an immunosuppressant].
AB  - A 44-year-old woman was admitted to our hospital complaining of dyspnea. A chest
      X-ray film obtained on admission showed bilaterally shrunken lungs, and
      peripheral bundle-like and linear shadows. A chest CT scan revealed marked
      thickening of bronchovascular bundles and low lung volumes. Mild dryness of the
      mouth, and the results of a Rose-Bengal test, Schirmer test, and sialography led
      to the diagnosis of primary Sjogren's syndrome. Corticosteroid pulse therapy was
      followed by slight improvement. To determine the pathological diagnosis and to
      plan further therapy, video-assisted thoracoscopic lung biopsy was done.
      Examination of the biopsy specimen revealed alveolitis and infiltration of
      lymphocytes, which suggested active interstitial pneumonia. Therapy with
      corticosteroids and the immunosuppressant azathioprine was followed by marked
      improvement.

PMID- 9168650
TI  - [Juvenile onset of idiopathic interstitial pneumonia].
AB  - A 22-year-old first man came to our hospital because of dyspnea on exertion in
      February 1993, and was admitted in September 1994 because of progression of
      dyspnea. A chest roentgenogram showed diffuse ground-glass-opacities in the
      middle and lower lung fields, and an elevated diaphragm. Pulmonary-function
      testing revealed a low %VC and a low diffusing capacity. Examination of a
      specimen obtained by thoracoscopic lung biopsy revealed usual interstitial
      pneumonia. Immunohistochemical examinations showed the expression of
      intercellular adhesion molecule-1 on vascular endothelial cells and on alveolar
      epithelial cells. Dust inhalation and collagen vascular disease were ruled out
      and the diagnosis was idiopathic interstitial pneumonia. This condition develops
      only rarely in patients under 60 years old.

PMID- 9168651
TI  - [Systemic sarcoidosis with involvement of the spermatic cord].
AB  - A 49-year-old man presented with an enlarging, painful, right inguinal mass and
      small red nodules around his nose and upper lip. He had undergone an operation
      for a right inguinal hernia in childhood. Because malignancy was suspected, the
      right spermatic cord, testis, and epididymis were resected. Histological
      examination of the lesion in the spermatic cord revealed non-caseating
      epithelioid-cell granuloma and no acid-fast bacilli, which was compatible with
      sarcoidosis. A chest X-ray film and computed tomograms showed enlarged hilar
      lymph nodes and reticular infiltrates. Histological examination of specimens
      obtained by transbronchial lung biopsy and by skin biopsy also showed non
      caseating epithelioid-cell granulomas. After resection of the spermatic cord, the
      activity of angiotensin-converting enzume was 29.9 IU/L, which was above the
      reference range. Systemic sarcoidosis with involvement of the spermatic cord was
      diagnosed. Because he had no respiratory symptoms and his skin lesions resolved
      without treatment, he is currently under observation and is not receiving
      corticosteroid therapy.

PMID- 9168652
TI  - [Alveolar hemorrhage and glomerulonephritis in two patients with anti-neutrophil
      cytoplasmic antibodies].
AB  - A 55-year-old woman and a 56-year-old woman were admitted to the hospital because
      of dyspnea on exertion and bloody sputum. Chest roentgenography and computed
      tomography showed bilateral infiltrative shadows. Examination of bronchoalveolar
      lavage fluid and of specimens obtained by transbronchial lung biopsy revealed
      alveolar hemorrhage and hemosiderin-laden macrophages. Examination of specimens
      obtained by needle biopsies of the kidneys showed glomerulonephritis. Test for
      anti-neutrophil cytoplasmic antibody (ANCA) were positive; alveolar hemorrhage
      and glomerulonephritis accompanied by ANCA-related vasculitis was diagnosed. The
      patients' condition improved with administration of prednisolone and
      cyclophosphamide. Measurement of ANCA was useful for monitoring the activity of
      the disease.

PMID- 9168653
TI  - [A mesenchymal malignant mesothelioma that changed from mixed type to purely
      sarcomatous type].
AB  - A 65-year-old man was admitted to the hospital because of an abnormal shadow on a
      chest roentgenogram. A diagnosis of mixed-type malignant mesothelioma was made
      after transcutaneous needle biopsy and thoracoscopic biopsy. The tumor was
      considered to be inoperable because it had diffusely invaded surrounding tissue,
      and therefore the patient was treated with chemotherapy only. About one year
      later, he died of acute pneumonia. At autopsy, a mesenchymal malignant
      mesothelioma that did not have an epithelial component was found. We know of no
      previous report of a case in which a tumor with a biopsy-proven epithelial
      component apparently changed to a purely sarcomatous type. No satisfactory
      explanation for this phenomenon has been offered.

PMID- 9168654
TI  - [Lymphocytic interstitial pneumonia associated with Sjogren's syndrome and
      mediastinal lymphadenopathy: diagnosis by open-lung biopsy].
AB  - A 56-year-old woman was admitted to the hospital because of dry coughing and
      shortness of breath on exertion. In addition, dry eyes and cornea guttata
      suggested Sjogren's syndrome. Chest radiography revealed linear, reticular
      shadows throughout the lung fields, and enlargement of hilar and mediastinal
      lymph nodes. A specimen was obtained by transbronchial lung biopsy but the
      findings were not condusive; open-lung biopsy was done. The histopathological
      findings suggested lymphocytic meterstitial pneumonia. Results of genetic
      analysis and of immuno-histochemical examination conformed that the proliferating
      lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have
      been used to treat lymphocytic interstitial pneumonia, and they were effective in
      this case.

PMID- 9168655
TI  - [Allergic bronchopulmonary aspergillosis successfully treated with itraconazole].
AB  - A 67-year-old man was admitted to our hospital because of coughing, a low-grade
      fever, and abnormal shadows on a chest X-ray film. He had had asthma as a child,
      but had no asthmatic symptoms on admission. A CT scan showed collapse of the
      right middle lobe and mucoid impactions in the lingula. Bronchoscopy revealed
      thick mucus obstructing the right middle-lobe bronchus and the left upper-lobe
      bronchus. The eosinophil count and the IgE level were abnormally high.
      Aspergillus fumigatus was detected in his sputum. Tests for immediate skin
      reaction and precipitating antibody to aspergillus antigen were positive. After
      treatment with itraconazole he became asymptomatic. Radiographic abnormalities
      had resolved by 1 month after the start of treatment; a high resolution CT scan
      obtained after clinical improvement revealed central bronchiectasis. In this
      patient with allergic bronchopulmonary aspergillosis, a course of itraconazole
      alone was followed by satisfactory improvement.

PMID- 9168656
TI  - [Effects of bilateral lung volume reduction surgery in a patient with severe
      pulmonary emphysema].
AB  - A 61-year-old man suffering from severe pulmonary emphysema underwent lung volume
      reduction surgery on both upper lobes. By one year after surgery functional
      residual capacity had decreased by 2.5 L and FEV1 had increased by a factor of
      2.4. Diaphragm excursion, as assessed by dynamic magnetic resonance imaging, had
      increased and ventilation and pulmonary gas exchange had improved. Performance on
      a 6-minute-walk test and exercise tolerance measured on a bicycle ergometer
      improved, and both peak VE and VO2 increased. Before surgery, pulmonary artery
      pressure Ppa and pulmonary capillary wedge pressure Pewp during exercise were
      abnormally high, but 6 months after the operation the increases in Ppa and Pcwp
      during exercise were markedly reduced.

PMID- 9168657
TI  - [Central sleep apnea syndrome successfully treated with nasal bi-level positive
      airway pressure and sleep position adjustment].
AB  - A 55-year-old obese man was admitted to our hospital because of a severe morning
      headache. He snored and had recurrent episodes of sleep apnea that began 10 years
      earlier and had since become much worse. An overnight polysomnographic recording
      confirmed that he had sleep apnea syndrome, predominantly of the central type.
      The apneas were more frequent when he lay on his back (apnea index 54.5) than on
      his side (apnea index 1.2). He was treated with sleep position adjustment and
      nasal bi-level positive airway pressure, inspiratory positive airway pressure at
      5 cmH2O and expiratory positive airway pressure at 2 cmH2O. His snoring,
      headache, and oxygen desaturation resolved. This case suggests that airway
      collapse may cause central apnea, and that nasal continuous positive airway
      pressure, and nasal bi-level positive airway pressure and adjustment of sleep
      position can be effective in some patients with central-type sleep apnea
      syndrome.

PMID- 9168658
TI  - [Kartagener's syndrome with aspergilloma].
AB  - A 47-year-old man was referred to our hospital because of hemoplysis. He had a
      history of chronic sinusitis and surgical treatment of a spinal arteriovenous
      malformation. A chest X-ray film and computed tomographic scan showed
      dextrocardia, diffuse bronchiectasis, and an aspergilloma in the right upper lung
      field. The source of the bleeding could not be detected by fiberoptic
      bronchoscopy. Transbronchial mocosal biopsy was done and examination of a
      specimen by transmission electron microscopy revealed the lack of inner and outer
      dynein arms. A chest X-ray film and computed tomographic scan of his nephew, who
      had a long history of productive cough showed dextrocardia and right lower-lobe
      bronchiectasis. These findings indicate that hemoptysis in patients with
      Kartagener's Syndrome can be caused not only by bronchiectasis but also by
      aspergilloma.

PMID- 9168659
TI  - [Mycoplasma pneumoniae pneumonia with diffuse nodular shadows and right hilar
      lymphadenopathy].
AB  - A 51-year-old man was admitted to our hospital because of fever, a productive
      cough, and dyspnea. His chest X-ray film revealed diffuse reticulonodular shadows
      and right hilar lymphadenopathy. A chest CT scan revealed thickened bronchial
      walls and diffuse centriacinar or centrilobular nodular shadows. Serologic
      testing provided conclusive evidence of Mycoplasma pneumoniae infection. The
      diffuse pattern and hilar lymphadenopathy on chest X-ray films are uncommon in
      this disease, and they caused some uncertainty regarding the correct diagnosis.
      M. pneumoniae attaches to cells of the respiratory tract and produces a locally
      acting cytotoxin. Immunologic mechanisms have been shown to play an important
      role in the pathogenesis of pneumonia. This case suggests that immunologic
      mechanisms are an important factor in diffuse lung lesions.

PMID- 9168660
TI  - Relationship between the presenting symptoms and age at diagnosis in alcoholic
      and nonalcoholic chronic pancreatitis: analysis of 164 patients.
AB  - OBJECTIVE: To study the different forms of presentation, patient age, delay in
      diagnosis and incidence of calculi in alcoholic and nonalcoholic chronic
      pancreatitis. METHODS: We have studied 130 men and 34 women diagnosed as having
      chronic pancreatitis on the basis of clinical criteria and morphological and/or
      functional tests. RESULTS: Alcohol was the most common cause of chronic
      pancreatitis in men (89.1%) existing a significant difference with respect to
      women (p < 0.05). The mean age of the patients with alcoholic chronic
      pancreatitis was 45.6 +/- 11.3 years and that of patients presenting nonalcoholic
      chronic pancreatitis was 54.5 +/- 11.5 years (p < 0.01), the latter showing a
      bimodal distribution. The ages of the patients in whom the presenting symptom was
      abdominal pain and acute inflammatory episodes were 43.9 +/- 12.8 and 45.3 +/-
      13.5 years, respectively, significantly lower (p < 0.05) than the age of patients
      in whom presentation was signaled by the onset of diabetes or diarrhea (53.1 +/-
      11.2 and 61.2 +/- 12.9 years, respectively). Statistically significant
      differences existed in the delay in diagnosis when comparing the patients before
      and after 1985 (12.3 +/- 14.5 years, range 0 to 50 years, versus 0.42 +/- 0.9
      years, range 0 to 5 years; p = 0.005). At diagnosis, 14.3% of the patients whose
      presenting symptom was acute pancreatitis had pancreatic calculi, versus 42.2% of
      those who reported abdominal pain as the first indication. CONCLUSIONS: Alcoholic
      chronic pancreatitis predominates in men. Nonalcoholic chronic pancreatitis
      presents two peaks of prevalence. A substantial number of patients may remain
      pain-free up to diagnosis. Calculi are not uncommon during the initial period of
      chronic pancreatitis when pain is the presenting symptom, either in the form of
      isolated episodes of abdominal pain or attacks of acute pancreatitis.

PMID- 9168661
TI  - Usefulness of rectal dialysis to determine intrarectal eicosanoids release in
      ulcerative colitis.
AB  - The quantification of the local production of eicosanoids is of interest because
      it has been implicated in the mucosal damage of ulcerative colitis. In situ
      production of eicosanoids is not reflected by its urinary or seric levels,
      requiring invasive examinations. Thus, new non-invasive techniques such as rectal
      dialysis have been investigated. The purpose of this study was to assess whether
      the determination of the intrarectal eicosanoid levels measured by rectal
      dialysis is useful in detecting the presence of rectal inflammation in patients
      with ulcerative colitis. Thirty one patients with clinically active colitis and 7
      controls with irritable bowel syndrome have been studied. A 10 cm long dialysis
      bag was placed in the rectum for 1 hour. To determine the variability of the
      technique, the dialysis was repeated the next day in 6 controls. To detect
      intrarectal eicosanoids release in inactive colitis, rectal dialysis was
      performed in another group of 15 patients with clinical and endoscopically
      inactive colitis and compared with 9 patients with active colitis. PGE2, TXB2,
      and LTB4 were measured in rectal dialysates by immunospecific RIA. Dialysis was
      well tolerated by all participants. Intrarectal level of every eicosanoid was
      much higher in active colitis than in controls (p < 0.05) and in inactive colitis
      (p < 0.001). The mean coefficient of variation of duplicated dialysis ranged from
      15 to 28%. In conclusion, rectal dialysis is a non-invasive technique that allows
      to prove the presence of active inflammation in ulcerative colitis patients.

PMID- 9168662
TI  - Bacteremia following liver biopsy in transplant recipients with Roux-en-Y
      choledochojejunostomy.
AB  - Between 1990 and 1995, 666 percutaneous liver biopsies were performed in 196
      patients at Gregorio Maranon General Hospital (mean 3.4 biopsies/patient); 533
      biopsies (80.03%) were carried out in patients with choledochostomy biliary
      anastomosis and 133 (19.97%) in patients with choledochojejunostomy. Infectious
      complications, in the form of sepsis, occurred in two patients, who recovered
      favorably with antibiotic therapy. These two patients had undergone Roux-en-Y
      choledochojejunostomy (1.5%, not significant). Our findings suggest that the
      incidence of infectious complications after liver biopsy in transplant recipients
      is very low. Antibiotic prophylaxis at the time of liver biopsy in patients with
      Roux-en-Y choledochojejunostomy may decrease the frequency of infectious
      complications.

PMID- 9168663
TI  - Ultrasound-guided fine-needle aspiration biopsy. Study of the cost per patient
      and comparison with computed tomography-guided biopsy.
AB  - Between February 1992 and July 1995, we performed 222 ultrasound-guided fine
      needle aspiration biopsies (FNAB) in abdominal space-occupying lesions. The
      sensitivity was 90% and the specificity, 100%, with an overall diagnostic
      precision of 93%. We also determined the cost of each procedure (2,550 pesetas)
      and compared it with the cost of computerized tomography (CT)-guided biopsy
      (22,500 pesetas). These results and those reported in the literature indicate
      that there is no significant difference with respect to diagnostic yield, but
      that the difference in terms of expense is considerable. We believe that, in the
      assessment of abdominal lesions. CT-guided FNAB should be reserved for those
      lesions that prove inaccessible to ultrasound.

PMID- 9168664
TI  - Reticular fibers in the stroma of the thymus.
AB  - There were investigated thymic biopsies taken from 14 children deceased of
      intercurrent diseases. After routine paraffin procedures, slides were stained
      with hematoxylin-eosin, Gordon-Sweet, Wilder and Laidlaw methods. Reticular
      fibers are described in the stroma and parenchyma of the thymus. Their number and
      thickness are higher in connective septa, perivascular sheaths, at the cortico
      medullary junction and around Hassall's bodies. Their involvement in a basal
      membrane like structure located between epithelio-reticular cells and thymocytes
      is discussed.

PMID- 9168665
TI  - There are no in vivo pulsations of mouse blastocysts.
AB  - An important event at the onset of the implantation process in mammals is the
      hatching of the blastocyst from the zona pellucida. Microcinematographic studies
      of in vitro preimplantation development in mice revealed the pulsatile activity
      of blastocysts before and during the hatching period. It is generally accepted-
      up to now--that the in vitro hatching is at least partially the result of
      repeated contractions and reexpansions of the blastocyst. The presence of
      pulsatile activity in vivo may confirm this hypothesis. Mouse blastocysts were
      obtained by a rapid flushing (5-10') from uterine horns on day 4 of pregnancy and
      the presence or absence of contracted blastocysts was noted. From 410 examined
      blastocysts only 3% were contracted as compared with the very frequent in vitro
      pulsations. This result suggests that in mice the in vivo pulsatile activity of
      blastocysts, practically, does not exist. The in vivo contractions are probably
      determined by the suboptimal culture conditions.

PMID- 9168666
TI  - Immunohistochemical aspects of chromogranins in endocrine cells of the duodenal
      mucosa in some primates.
AB  - Endocrine cells in the duodenal mucosa of some primates (Cercopithecus aetiops,
      Macaca cinomolgus-nemestrina and Macaca rhesus) have been studied with
      immunohistochemical methods for chromogranins. Material sampling immediately
      after death (by carotid bleeding concomitantly with formalin 10% perfusion) was
      helpful in the study of endocrine cells. The location and number of endocrine
      cells of the duodenal mucosa of the primates under study are generally similar to
      those of humans. The use of an antibody cocktail against all three Cgs/Sgs
      appears to be the method of choice to identify neuroendocrine granule-containing
      cells. When comparing the results of this study with those obtained by us in a
      previous work by silver staining, the Grimelius technique is recommended together
      with the immunohistochemical techniques for chromogranins in the practice of the
      usual diagnosis of the endocrine pathology.

PMID- 9168667
TI  - Fine needle aspiration biopsy of the liver.
AB  - There were investigated 51 patients admitted with suspicion of chronic hepatitis
      and secondary tumours of the liver. In all cases, fine needle aspiration biopsy
      was performed, and smears were fixed by drying and stained with BPT-Dragan and
      May Grunwald-Giemsa. In chronic hepatitis, the needle aspiration biopsy has a
      limited importance in the diagnosis because it cannot notice architectural
      features. The nucleo-cytoplasmic lesions are better observed. In secondary
      tumours of the liver, the aspiration biopsy, through simplicity and fidelity,
      represents the main method in the diagnosis. Cytological results were compared
      with histological ones. On smears we observed hepatocytes and atypical cells.

PMID- 9168668
TI  - Anatomoclinical and bacteriological study on chronic marginal periodontal
      disease. Therapy with staphylococcic vaccine.
AB  - Histological, histochemical and electronmicroscopic investigations were carried
      out on gum biopsies taken from cases with chronic marginal periodontal disease
      before and after the treatment with staphylococcic vaccine, thus,
      morphopathologically proving the findings of Gafar et al. (1985) and of Georgescu
      et al. (1973; 1974; 1975; 1979; 1995). Before treatment, gum lesions were severe,
      consisting in an abundance of polymorphic inflammatory infiltrates in the chorion
      along with oedema and disorganised connective fibres, atrophies and ulceration of
      the mucosa, purulent deposits at the surface with bacteria and fungi. After the
      treatment with the staphylococcic vaccine, an epithelial regeneration was seen
      together with the absence of the chronic inflammation. The intensely fibroparius
      granulated tissue was also noted, in all cases observing abundant connective
      fibres, accounting for good results after treatment, notably the firmness of the
      tooth fitting.

PMID- 9168669
TI  - The value of the ultrastructural pattern of myeloperoxidase (MPO), platelet
      peroxidase (PPO) and acid phosphatase in identification of blastic cell types
      during acute transformation of chronic myeloproliferative disorders (cMPD).
AB  - We established the cell line of bone marrow and blood cells provided by 19 cases
      of cMPD by ultrastructural studies of their enzymatic content. Myeloblasts,
      megakaryoblasts and lymphoblasts were identified by the presence of
      myeloperoxidase, platelet peroxidase and acid phosphatase, respectively.

PMID- 9168670
TI  - Morphopathological and clinical diagnosis aspects of a bilateral dysembryoplasic
      renal tumor associated with Bourneville's tuberous sclerosis.
AB  - A 34-year old woman was admitted for bilateral flank pain, maleolary and
      palpebral oedema with an insidious evolution lasting for 5 years. Urogram showed
      a left ureteral duplicity and a right lacunary pelvic image. MRI and echography
      indicated the complete modification as a renal structure as well as the presence
      of some bilateral tumoral formations with a nonhomogenous structure, blood
      diffusion and adenopathy of the renal hilum. Nephrectomy revealed white-gray
      tumoral nodular tumours. The histopathological test evidenced proliferations of
      leiomyofibromatous, angiomatous, lipomatous, cartilaginous types with a benign
      aspect suggesting the diagnosis of a renal dysembryoplasic tumor (hamartoma).

PMID- 9168671
TI  - Nucleolar organizer regions (AgNORs) in intraepithelial neoplasia of the uterine
      cervix.
AB  - The authors have studied the AgNORs counts in intraepithelial lesions of the
      uterine cervix. The following values were obtained (mean +/- SD AgNORs/cell):
      normal specimens--2.11 +/- 0.98; mild dysplasia--2.83 +/- 1.12; moderate
      dysplasia--3.42 +/- 1.13; severe dysplasia--3.55 +/- 1.28; carcinoma in situ-
      4.63 +/- 1.34; glandular extensions of carcinoma in situ--4.64 +/- 0.98. The
      values in moderate and severe dysplasia were similar, an argument for grouping
      these categories in the high-grade lesions. AgNORs counts in carcinoma in situ
      were, however, higher than in severe dysplasia, suggesting a continuous evolution
      of the neoplastic process.

PMID- 9168672
TI  - Study on the nucleolar organiser regions in soft tissue liposarcoma.
AB  - The authors studied 24 cases of liposarcoma of soft tissue included in two
      categories: myxoid liposarcoma and pleomorphic liposarcoma. The 24 tumors were
      stained by Ploton's method for revealing the nucleolar organiser regions
      (AgNORs). AgNORs were counted in the nuclei of 100 cells/case. AgNORs in the
      cells of some cases showed hyperchromasia and an increased size. The results
      suggest a role of AgNORs as a possible prognostic discriminator of different
      histological types.

PMID- 9168673
TI  - Disseminated Langerhans cell histiocytosis: a case report with a light
      microscopic and ultrastructural study.
AB  - A case of disseminated Langerhans cell histiocytosis (L.C.H.) in a 9 month-old
      boy is reported. The clinical picture was characterized by severe multivisceral
      involvement with cutaneous and bone lesions. Histological examination of the skin
      biopsy revealed diffuse infiltration of large mononucleated histiocytes admixed
      with a small number of inflammatory cells. Ultrastructural examination confirmed
      the Langerhans cell (L.C.) phenotype by showing intracytoplasmic Birbeck granules
      in the proliferating histiocytes. We report the histological and ultrastructural
      characteristics of our case and review the diagnostic features of L.C.H. in the
      light of the criteria established by the Writing Group of the Histiocytic Society
      in 1987.

PMID- 9168674
TI  - [Genome analysis of human chromosome 21: transcript mapping of the Down syndrome
      region].

PMID- 9168675
TI  - [Mechanism of transcription activation by FTZ-F1].

PMID- 9168676
TI  - [Expression of brain prolactin receptor mRNA and induction of maternal behavior].

PMID- 9168677
TI  - [Detection of bioradicals by in vivo ESR spectrometry].

PMID- 9168678
TI  - [Activation induces dephosphorylation of cofilin (an actin/PIP2-binding protein)
      and its translocation to plasma membranes in leukocytes].

PMID- 9168679
TI  - [Proteases participating in metamorphosis of flesh fly (Sarcophaga peregrina)].

PMID- 9168681
TI  - Satisfaction with access to and quality of health care among Medicare enrollees
      in a health maintenance organization.
AB  - This study was designed to determine the levels and predictors of Medicare
      enrollees' satisfaction with access to medical care and quality of health care in
      a health maintenance organization. Data collected by an instrument adapted from
      the Group Health Association of America's Consumer Satisfaction Survey were
      analyzed after being linked with administrative data. In general, Medicare
      enrollees reported high satisfaction with both access to and quality of health
      care. Most members (96%) rated skill, experience, and training of physicians and
      the friendliness and courtesy of the staff favorably. A lower percentage of
      members (77%) rated favorably the ability to contact a physician after hours.
      Levels of satisfaction were essentially not explained by patient characteristics
      such as age, sex, geographic region, medications, or utilization. Stepwise
      regression identified the ease of arranging appointments as the strongest
      predictor of satisfaction, with access to care and outcomes of medical care as
      the strongest predictor of overall satisfaction with quality of health care.
      These findings indicate that items that members rated least favorably, such as
      ability to contact a physician after hours, added little to the prediction of
      satisfaction with access to and quality of health care.

PMID- 9168682
TI  - A breast cancer care report card. An assessment of performance and a pursuit of
      value.
AB  - The transition to managed care raises concerns about the resulting quality of
      care. The report card, a publicly released, standardized report on quality, has
      received widespread acceptance as a method to evaluate physician performance.
      Current report cards provide insufficient information to allow purchasers of
      health care to assess accurately the performance of professionals who provide
      breast care. To overcome these limitations, we propose an expanded report card on
      breast cancer care. Mammographers and general surgeons would assess an
      independent series of at least 100 consecutive cases of newly diagnosed breast
      cancer. Mammographers would determine the percentage of invasive cancers < 15 mm
      detected on screening mammograms in asymptomatic women aged 50 to 74 years.
      Surgeons would determine the percentage of combined stages 0 and 1 breast cancers
      detected and the percentage of patients receiving breast-conserving surgical
      therapy. Performance targets are set at 60% for invasive cancers < 15 mm detected
      on screening mammography, 60% for combined stage 0 and 1 breast cancers, and 50%
      for patients receiving breast-conserving therapy.

PMID- 9168683
TI  - Management of acute ischemic stroke. An update for primary care physicians.
AB  - Few areas of medicine have had as many major advances in recent years as the
      treatment and prevention of ischemic stroke. During the 1990s-"the decade of the
      brain"-carotid endarterectomy was demonstrated to be effective for preventing
      stroke in patients with significant carotid stenosis. Large clinical studies have
      documented the effectiveness of new antiplatelet agents and oral anticoagulant
      therapy for stroke prevention in specific patients groups, and recently tissue
      plasminogen activator was approved for the treatment of acute ischemic stroke.
      Because the use of these new therapies is restricted to specific patient
      subgroups, the accurate determination of the cause of stroke is now mandatory.
      Fortunately, advances in diagnostic methods, including cardiac and vascular
      ultrasonographic techniques and brain imaging, facilitate the determination of
      the stroke subtype in most patients. Additional advances in stroke treatment and
      prevention are on the immediate horizon. New therapeutic agents, including
      neuroprotective medications, and new treatment modalities such as cerebral
      angioplasty are promising investigational therapies.

PMID- 9168684
TI  - Evaluation and treatment of primary esophageal motility disorders.
AB  - Achalasia, diffuse esophageal spasm, and nutcracker esophagus constitute the main
      primary esophageal motility disorders. During the past decade major progress has
      been made in understanding their pathophysiology and in the ability to establish
      a precise diagnosis. In addition, minimally invasive surgical intervention has
      radically changed the therapeutic approach, and thoracoscopic or laparoscopic
      myotomy is probably the best treatment for most patients.

PMID- 9168685
TI  - Osteoporosis in men with spinal cord injuries.

PMID- 9168686
TI  - New approaches to managing spasticity in children with cerebral palsy.

PMID- 9168687
TI  - New drugs for improving injury outcome in spinal cord injuries.

PMID- 9168688
TI  - Management of suffering in patients with severe burn injury.

PMID- 9168689
TI  - Monoamine oxidase inhibitor overdose.

PMID- 9168690
TI  - Eosinophilic tuberculous pleural effusion.

PMID- 9168691
TI  - Life's brief candle. A Shakespearean guide to death and dying for compassionate
      physicians.

PMID- 9168692
TI  - Oxygen saturation: a fifth vital sign?

PMID- 9168693
TI  - Answers to the right question.

PMID- 9168694
TI  - Primary esophageal motility disorders: incisive decisions.

PMID- 9168695
TI  - Psychological effects of chronic injury in elite athletes. Correction.

PMID- 9168696
TI  - From red goggles to Helicobacter pylori.

PMID- 9168697
TI  - Alteration of medical records.

PMID- 9168698
TI  - Chest teleradiology in a teaching hospital emergency practice.
AB  - OBJECTIVE: New standards for hospital accreditation and health care reimbursement
      may require that faculty subspecialists be more available after regular working
      hours to supervise residents in academic radiology departments. We designed a
      receiver operating characteristic study to determine whether a thoracic
      radiologist who evaluated computed radiography (CR) images of the chest at a home
      based teleradiology workstation could add significant value to a junior
      resident's interpretations of films within the hospital for acutely ill patients.
      SUBJECTS AND METHODS: Using a hybrid cassette, we obtained analog chest films and
      CR images simultaneously for each of 252 acutely ill patients in the emergency
      department and in an intensive care unit. Interpretations of the analog films by
      three first-year residents were analyzed for 11 parameters deemed critical for
      patient management. Likewise, CR images of the same chest studies were viewed on
      a home teleradiology workstation by a faculty thoracic radiologist who analyzed
      the images for these 11 interpretive parameters. All interpretations by radiology
      residents and by the home-based thoracic radiologist were then compared with the
      interpretations of a consensus panel consisting of another thoracic radiologist
      and a full-time emergency department radiologist. RESULTS: Analysis of the pooled
      results from the three junior residents as a group failed to show significant
      differences between their interpretations of chest films and the interpretations
      of CR images by a thoracic radiologist at a home workstation. However, we
      observed significant differences for several image interpretation parameters
      between individual residents and the home-based radiology subspecialist.
      CONCLUSION: The data confirm that significant value can be added to the
      interpretations of chest films by individual junior residents when a home-based
      thoracic radiologist uses teleradiology to provide expert interpretations.
      Accordingly, it is reasonable to infer that on-line supervision by faculty
      subspecialists via teleradiology could be used to complement the scheduled visits
      that are being made now by individual faculty members of our institution to
      interpret films periodically with a radiology resident during overnight and
      weekend periods.

PMID- 9168699
TI  - Helicobacter pylori and peptic ulcer disease: evolution to revolution to
      resolution.

PMID- 9168700
TI  - Helicobacter pylori and gastroduodenal diseases: a minor revolution for
      radiologists.

PMID- 9168701
TI  - Carcinoma of the esophagus and esophagogastric junction: sensitivity of
      radiographic diagnosis.
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity of barium
      studies in revealing carcinoma of the esophagus and esophagogastric junction.
      MATERIALS AND METHODS: We retrospectively reviewed 50 cases of squamous cell
      carcinoma of the esophagus (n = 25) and adenocarcinoma of the esophagus (n = 14)
      or esophagogastric junction (n = 11) in which double-contrast (n = 46) or single
      contrast (n = 4) barium studies had been done. The original radiology reports
      were reviewed to determine whether the lesions had been seen on barium studies
      and whether cancer had been diagnosed. Records were also reviewed to determine
      the number of patients who underwent esophageal endoscopy because of findings
      suggestive of cancer on barium studies at some point from January 1992 through
      December 1992. Pathology records were then reviewed to determine the number of
      true- and false-positive barium studies during this same period. RESULTS: Lesions
      were shown on barium studies in 49 (98%) of 50 patients, and carcinoma of the
      esophagus or esophagogastric junction was diagnosed or suspected in 48 patients
      (96%). In a separate part of the study, we found that endoscopy had been
      recommended to rule out malignant tumor in only 26 (1%) of 2484 patients who
      underwent barium studies at some point from January 1992 through December 1992.
      Endoscopy revealed cancer in 11 of those 26 patients; the remaining 15 were
      assumed to have false-positive radiologic examinations. Barium studies therefore
      had a positive predictive value of 42%. CONCLUSION: The double-contrast barium
      study is a sensitive technique for the diagnosis of carcinoma of the esophagus
      and esophagogastric junction. This high sensitivity can be achieved while
      recommending endoscopy in only about 1% of all patients who undergo barium
      studies.

PMID- 9168702
TI  - Accuracy of staging rectal tumors with contrast-enhanced transrectal MR imaging.
AB  - OBJECTIVE: Our objective was to evaluate the accuracy of contrast-enhanced
      transrectal MR imaging in staging rectal adenoma and carcinoma by correlating
      with histopathologic findings. SUBJECTS AND METHODS: Thirty-five patients
      underwent transrectal MR imaging on a 1.5-T superconducting unit using unenhanced
      T1-weighted and T2-weighted spin-echo and turbo spin-echo sequences, a dynamic
      gadopentetate dimeglumine-enhanced turbo fast low-angle shot sequence, and
      enhanced T1-weighted spin-echo sequences. For all patients, histopathologic
      correlation was available from biopsy (n = 15) or surgical resection (n = 20).
      Two radiologists unaware of each other's interpretations of the scans interpreted
      each case from which we evaluated qualitative and quantitative data. RESULTS:
      Rectal adenomas (n = 15) were identified when imaging revealed an intact
      muscularis mucosae, a homogeneous internal structure, and high contrast
      enhancement of the lesion. Carcinomas staged as T1 by TNM criteria (n = 6) were
      best revealed by dynamic turbo fast low-angle shot sequences, in which an intact
      muscularis propria could be seen. Visualization of enhancing tumor tissue in the
      muscularis propria indicated T2 carcinoma (n = 5). All T3 (n = 5) and T4 (n = 4)
      carcinomas were correctly staged with dynamic and static MR imaging. The stage
      revealed by MR imaging correlated well with histologic staging results in 89%
      (observer 1) and 86% (observer 2) of interpretations. However, when interpreting
      MR imaging, observers tended to overstage and never understaged. CONCLUSION:
      Transrectal surface-coil MR imaging provided reliable information in staging
      patients before surgery and in evaluating rectal adenoma and carcinoma.

PMID- 9168703
TI  - Transvaginal versus anal endosonography for detecting damage to the anal
      sphincter.
AB  - OBJECTIVE: We undertook this study to establish the accuracy of transvaginal
      endosonography for detecting damage to the anal sphincter. SUBJECTS AND METHODS:
      Anal endosonography was performed in 47 parous patients and one nulliparous
      patient using a sonographic scanner, an 1850 endoprobe, and a 10-MHz transducer
      protected by a water-filled hard plastic cone. This procedure was followed by
      transvaginal sonography using the same system but with a water-filled balloon in
      43 and a dedicated vaginal probe Type 8551 of 10-MHz frequency in five. Axial
      images were obtained as low in the perineum as possible. The transvaginal images
      were reviewed with the observer unaware of the findings from anal endosonography
      and were then compared with the anal endosonograms. RESULTS: The transvaginal
      images were inadequate for review in three patients. In the remaining 45
      patients, anal endosonography showed internal sphincter defects in 18 and
      external sphincter tears in 21. Transvaginal endosonography showed eight internal
      and 10 external sphincter defects only, giving a sensitivity of 44% and a
      specificity of 96% for the detection of internal sphincter defects and a
      sensitivity of 48% and a specificity of 88% for external sphincter tears.
      CONCLUSION: Transvaginal examination is not accurate for assessing the anal
      sphincter because of the anatomic limitations this approach imposes on axial
      imaging of the anal canal.

PMID- 9168704
TI  - Local staging of pancreatic cancer: criteria for unresectability of major vessels
      as revealed by pancreatic-phase, thin-section helical CT.
AB  - OBJECTIVE: This study was conducted to determine the criteria for unresectability
      of major peripancreatic vessels in patients with pancreatic carcinoma as revealed
      by optimally enhanced, pancreatic-phase thin-section helical CT. SUBJECTS AND
      METHODS: Twenty-five patients with pancreatic adenocarcinoma who underwent local
      dissection during curative or palliative surgery also underwent preoperative
      pancreatic-phase thin-section helical CT (40- to 70-sec delay, 2.5- to 3-mm
      collimation). Tumor involvement of the portal and superior mesenteric veins and
      the celiac, hepatic, and superior mesenteric arteries was prospectively graded on
      a 0-4 scale based on circumferential contiguity of tumor to vessel. Subsequent
      surgical results were then correlated with the CT grades. RESULTS: At surgery,
      definitive evaluation was possible for 80 vessels. Forty-eight of 48 vessels
      graded 0 and three of three vessels graded 1 were resectable. Four of seven
      vessels graded 2, seven of eight vessels graded 3, and 14 of 14 vessels graded 4
      were unresectable. A threshold of between grades 2 and 3, which corresponded to
      tumor involvement of one-half circumference of the vessel, yielded the lowest
      number of false-negatives and an acceptable number of false-positives for
      unresectability. Such a threshold would have yielded a sensitivity of 84%, a
      specificity of 98%, a positive predictive value of 95%, and a negative predictive
      value of 93% for unresectability of the vessels studied. CONCLUSION: A grading
      system for tumor involvement of the major vessels in patients with pancreatic
      adenocarcinoma can be based on the degree of circumferential contiguity of tumor
      to vessel. Involvement of vessel to tumor that exceeds one-half circumference of
      the vessel is highly specific for unresectable tumor.

PMID- 9168705
TI  - Correlation of the arterial resistive index in pancreas transplants of patients
      with transplant rejection.
AB  - OBJECTIVE: This study was undertaken to determine whether arterial resistive
      indexes (RIs) in pancreas transplants correlate with biopsy-proven transplant
      rejection. MATERIALS AND METHODS: We retrospectively reviewed arterial RIs in
      pancreas transplants for all patients who underwent Doppler sonography within 1
      week before transcystoscopic or percutaneous biopsy of pancreas transplants. RIs
      were correlated with type and degree of rejection in the 20 transplants for which
      biopsies provided sufficient tissue for diagnosis. Three patients were
      subsequently eliminated from the study because of significant intervening therapy
      between sonography and biopsy. RESULTS: The nine transplants with no evidence of
      rejection had a mean arterial RI of 0.64 (range, 0.49-0.80). The six transplants
      with acute mild or moderate rejection had a mean RI of 0.67 (range, 0.56-0.73).
      The two transplants with acute severe rejection had a mean RI of 0.85 (range,
      0.80-0.90). We found no statistically significant difference between arterial RIs
      in pancreas transplants of patients with acute mild or acute moderate rejection
      and those with no evidence of rejection. CONCLUSION: Arterial RIs of pancreas
      transplants do not differentiate between acute mild or acute moderate rejection
      and absence of rejection. The higher mean value of arterial RIs in pancreas
      transplants with acute severe rejection suggests that elevated arterial RIs are
      sensitive, but not specific, for revealing acute severe rejection of pancreas
      transplants. However, our study data are limited, and a larger sample size is
      necessary to draw statistically significant conclusions.

PMID- 9168706
TI  - In vitro and clinical studies of image acquisition in breath-hold MR
      cholangiopancreatography: single-shot projection technique versus multislice
      technique.
AB  - OBJECTIVE: This study was undertaken to compare the in vitro and clinical value
      of two-dimensional multislice breath-hold MR cholangiopancreatography (MRCP) with
      a single-shot projection technique using a half-Fourier acquisition single-shot
      turbo spin-echo sequence. SUBJECTS AND METHODS: We examined 108 patients with
      pancreaticobiliary diseases, using breath-hold MRCP and a half-Fourier
      acquisition single-shot turbo spin-echo sequence on a 1.5-T MR unit with a body
      phased-array coil. Two data acquisition techniques were employed: multislice
      acquisition postprocessed by maximum intensity projection (MIP) (multislice
      technique) and single-shot projection with a thick slice (projection technique).
      In the multislice technique, nine contiguous slices were obtained with a
      thickness of 5 mm (acquisition time. 18 sec). In the projection technique, a
      single slice was obtained with a thickness of 30, 50, or 70 mm (acquisition time.
      2 sec). Contrast-to-noise ratio (CNR) between the common bile duct and the liver
      as well as detectability of normal structures and diseases were compared for
      these two acquisition techniques. In the multislice technique, source images were
      also evaluated. ERCP or percutaneous transhepatic cholangiography images were
      used as the gold standard. RESULTS: Most of the pancreatic duct and common bile
      duct was revealed on 54% and 100% of the projection images, respectively, and on
      35% and 98% of the MIP images, respectively, CNR was significantly higher with
      the multislice technique than with the projection technique (p < .01). With the
      projection technique, CNR decreased as slice thickness increased. Dilatation and
      occlusion of the pancreaticobiliary tree were equally well revealed by the two
      imaging techniques. However, abnormalities in the periampullary region and
      anomalies in the pancreaticobiliary tree were more clearly seen on projection
      images than on MIP images (p < .05). Stones in the common bile duct, gallbladder,
      or intrahepatic bile duct were best seen on source images acquired by the
      multislice technique (83% sensitivity). CONCLUSION: Because of the absence of
      misregistration and the speed of image acquisition, breath-hold single-shot MRCP
      using the projection technique with a slice thickness of 30 or 50 mm consistently
      revealed the pancreaticobiliary tree and periampullary region with an acceptable
      CNR. Stones in the bile duct were best seen on the source images acquired by the
      MIP technique.

PMID- 9168707
TI  - Still the great mimicker: abdominal tuberculosis.
AB  - Since the mid 1980s, a resurgence of tuberculosis has occurred. The disease is
      and will remain a serious public health threat worldwide. The clinical and
      radiologic features of abdominal tuberculosis may mimic those of many diseases.
      Radiologists evaluating abdominal images should consider the diagnosis of
      abdominal tuberculosis in immigrants from areas endemic for tuberculosis, in
      immunocompromised patients, and in high-risk patients such as the homeless.
      Imaging features that suggest the correct diagnosis are cecal amputation,
      ileocecal thickening and inflammation, shortening of the ascending colon, gaping
      of the ileocecal valve, mesenteric adenopathy, a misty mesentery, diffuse omental
      infiltration, loculate high-density ascites, an enhancing peritoneum with or
      without an omental line, nodularity of the surface of the mesenteric leaves, and
      transperitoneal permeation.

PMID- 9168708
TI  - Malignant autonomic nerve tumor of the duodenum.
AB  - GAN tumors are rare and their diagnosis and distinction from other
      gastrointestinal stromal tumors is based on electron microscopy findings.
      Although no specific distinctive diagnostic imaging features are seen, this
      diagnosis should be considered when a large solid mass adjacent to a bowel loop
      shows the presence of air.

PMID- 9168709
TI  - Design and implementation of an interventional MR imaging suite.

PMID- 9168710
TI  - MR arthrography: a review of current technique and applications.

PMID- 9168711
TI  - Injury of the posterior ligament complex in patients with acute spinal trauma:
      evaluation by MR imaging.
AB  - OBJECTIVE: We undertook this study to use MR imaging to determine the frequency
      of injury to the posterior ligament complex of the thoracolumbar spine in
      patients who have undergone acute thoracolumbar trauma. SUBJECTS AND METHODS:
      Sixty-eight patients with varying severity of thoracolumbar trauma were examined
      prospectively. The majority of injuries were related to motor vehicle accidents.
      The second most common cause was falls. Patients were examined with plain
      radiography and MR imaging. In addition to conventional MR imaging sequences
      consisting of T1-weighted and fast spin-echo T2-weighted sagittal and axial
      images, a fat-suppressed T2-weighted sagittal sequence was performed. The
      findings were correlated with surgery in six cases and with follow-up clinical
      examination that included physical examination and conventional anteroposterior
      and lateral radiographs. RESULTS: Posterior ligament complex injury was detected
      in 53% (n = 36) of all patients. Such injury was most common in patients with
      flexion-distraction (n = 15) and patients with dislocation fracture (n = 4). Of
      the patients with dislocation fracture, all had posterior ligament complex
      injury. Of the 24 patients with burst fractures, posterior ligament complex tear
      occurred in 42% (n = 10). Of the 23 patients with compression fractures, 26% (n =
      6) had posterior ligament complex tear. Injury to the interspinous ligaments
      occurred with decreasing frequency in patients with injury to the supraspinous
      ligament, flaval ligaments, posterior longitudinal ligament, and anterior
      longitudinal ligament. Surgical findings correlated with MR imaging in all six
      patients who underwent surgery. CONCLUSION: Injury to the posterior ligament
      complex, which is often encountered in patients with burst and compression
      fractures, can be reliably revealed by MR imaging.

PMID- 9168712
TI  - Using MR imaging to diagnose partial tears of the anterior cruciate ligament:
      value of axial images.
AB  - OBJECTIVE: The purpose of this study was to determine the usefulness of axial MR
      imaging for diagnosing partial anterior cruciate ligament (ACL) tears and to
      determine if patients could be categorized as having stable or unstable partial
      ACL tears on the basis of criteria of axial MR imaging. MATERIALS AND METHODS: We
      reviewed 238 patients who, over a 2-year period, underwent both MR imaging of the
      knee and arthroscopic evaluation of the ACL. According to arthroscopic
      examination, these patients had 143 normal ACLs, 67 complete ACL tears, and 28
      partial tears. The 28 partial tears included 20 stable tears (no ACL deficiency)
      and eight unstable partial tears having ACL deficiency or requiring ACL
      reconstructive surgery. The axial MR images were retrospectively reviewed by two
      interpreters who were unaware of the arthroscopic findings, and decisions were
      reached by consensus. The ACL was classified according to its axial configuration
      and continuity. RESULTS: By axial MR imaging criteria, we found 109 elliptical
      ACLs, 45 attenuated ACLs, three ACLs with increased intrasubstance signal
      intensity, six isolated ACL bundle signs, 19 ACLs that could not be visualized,
      and 56 cloudlike mass signs. Arthroscopically normal ACLs and stable partial
      tears were difficult to distinguish reliably on axial MR images. Unstable partial
      ACL tears could not be distinguished from complete ACL tears. However, using
      axial MR imaging, our observers were able to segregate stable ACLs (normal
      ligaments and stable partial tears) from unstable ACLs (unstable partial tears
      and complete tears) with 100% sensitivity and 96% specificity. CONCLUSION: Axial
      MR imaging of the ACL may provide important diagnostic information for patients
      who have ACL injury. On axial MR images, stable ACLs were elliptical, attenuated,
      or showed as areas of increased intrasubstance signal intensity. At arthroscopy,
      attenuated ACLs represented normal ACLs (76%) and stable partial tears (24%). On
      axial MR images, the configurations that indicated unstable ligaments were
      isolated ACL bundle, nonvisualized ACL, and cloudlike mass.

PMID- 9168713
TI  - Normal patellar retinaculum: MR and sonographic imaging with cadaveric
      correlation.
AB  - OBJECTIVE: The purpose of our study was to define retinacular anatomy with MR
      imaging and sonography. MATERIALS AND METHODS: Five cadaveric knee specimens
      underwent sonography and MR imaging using the following sequences: T1-weighted
      axial, sagittal, coronal, and five oblique planes and axial three-dimensional
      gradient-echo imaging. Three knees were injected with gelatin gadolinium solution
      before imaging. All five specimens were sectioned. Correlation was made between
      findings derived from MR imaging, sonography, and cadaveric sections. RESULTS: T1
      weighted axial images without intraarticular gadolinium were most useful for
      revealing the superficial layer and deep ligaments of the retinacula; however,
      the oblique sagittal and oblique coronal planes showed the deep ligaments more
      clearly in their craniocaudal dimensions. Sonography revealed the retinacula as
      bilaminar structures with discrete superficial and deep layers but failed to
      distinguish the deep ligaments from one another. CONCLUSION: Conventional T1
      weighted axial MR images showed the various components of the retinacula
      including the medial patellofemoral ligament, which is an important stabilizing
      structure. Oblique imaging planes may be a helpful adjunct to axial imaging
      planes. Sonography can consistently identify the retinacula and may be useful in
      their assessment.

PMID- 9168714
TI  - Measurements of cortical thickness in experimentally created endosteal bone
      lesions: a comparison of radiography, CT, MR imaging, and anatomic sections.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of cortical
      measurements of experimentally created endosteal cortical lesions and to assess
      the sensitivity of radiography, CT, and MR imaging in the detection and
      measurement of such lesions. MATERIALS AND METHODS: Thirty-six cortical lesions
      were created in three fresh cadaveric femurs. After performing radiography, CT,
      and MR imaging, we sectioned the specimens in the axial plane. We then measured
      the remaining cortex at the lesions and the normal cortex adjacent to the lesions
      on all images and corresponding anatomic sections. The measurements of thickness
      of the cortex as seen with the different imaging methods and the anatomic
      sections were compared. Measurements were repeated to evaluate the influence of
      different window settings on the MR imaging measurements. RESULTS: When measured
      on radiographs, cortical thickness was overestimated in 58% of lesions. With CT,
      cortical thickness was overestimated by 0-15% in 94% of all lesions. With MR
      imaging, cortical thickness was uniformly underestimated by 3-17%. Measurements
      made on MR images varied according to different window settings. The proton
      density-weighted sequence yielded the highest sensitivity in the detection of
      shallow cortical lesions; the T1-weighted spin-echo sequence was the least
      sensitive of the MR sequences. CONCLUSION: In our cadaveric study, cortical
      thickness in the presence of endosteal lesions was overestimated on radiographs
      and CT scans and underestimated on MR images. Measurements derived from MR
      imaging are strongly influenced by the window setting. MR imaging with the proton
      density-weighted sequence is the most sensitive for detection of shallow cortical
      lesions and is more sensitive than CT.

PMID- 9168715
TI  - Symptomatic osteochondromas: imaging features.

PMID- 9168716
TI  - MR imaging diagnosis of triangular fibrocartilage pathology with arthroscopic
      correlation.
AB  - OBJECTIVE: The goal of this study was to compare MR imaging with arthroscopy in
      evaluating triangular fibrocartilage (TFC) pathology. MATERIALS AND METHODS: The
      results of 178 MR imaging examinations of the wrist were independently reviewed
      by two musculoskeletal radiologists who were unaware of the the clinical history,
      including any subsequent surgery. One hundred forty-nine of these studies were
      obtained from symptomatic patients. Of these patients, 56 underwent arthroscopic
      evaluation of the TFC. The remaining 29 studies were obtained from control
      volunteers and duplicate cases to reduce bias. The data were divided into
      categories based on Palmer's classification of TFC injury. Diagnostic
      sensitivity, specificity, and accuracy were calculated for each category.
      RESULTS: Of the 56 patients who underwent arthroscopic evaluation of the TFC, 27
      had TFCs that were intact at surgery. Also, 27 complete perforations and two
      partial defects were found at surgery. Sensitivity for detecting central
      degenerative perforations was 91% for both observers I and II. Sensitivity for
      detecting radial slitlike tears was 100% and 86% for observers I and II,
      respectively. Sensitivity for detecting ulnar-sided avulsions was 25% and 50% for
      observers I and II, respectively. CONCLUSION: MR imaging is accurate in revealing
      TFC perforations.

PMID- 9168717
TI  - MR imaging of rotator cuff tendon tears: comparison of T2*-weighted gradient-echo
      and conventional dual-echo sequences.
AB  - OBJECTIVE: Although MR imaging evaluation of the rotator cuff is usually done
      with proton density- and T2-weighted spin-echo techniques, interest also exists
      in T2*-weighted gradient-recalled echo techniques. The shorter scan times of T2*
      weighted sequences can be used to increase the number of signal averages and thus
      improve the signal-to-noise ratio. Our purpose in this study was to compare the
      sensitivity and specificity of oblique coronal T2*-weighted MR image
      interpretations with conventional dual-echo T2-weighted MR image interpretations
      when diagnosing rotator cuff tears. SUBJECTS AND METHODS: Forty-seven consecutive
      patients who underwent both MR imaging and shoulder arthroscopy were included in
      this study. The MR examination included both a 7 min 20 sec acquisition time
      proton density- and T2-weighted oblique coronal sequence and a 7 min 5 sec T2*
      weighted oblique coronal sequence. The oblique coronal dual-echo T2-weighted
      images were evaluated by two of the authors independently, who were unaware of
      the arthroscopic findings. Each of the two observers graded each cuff as being
      intact, having a partial-thickness tear, or having a full-thickness tear. After a
      3-week interval, each of the two observers then interpreted the T2*-weighted
      oblique coronal MR images in the same manner. Sensitivity and specificity for the
      two sets of interpretations were calculated in terms of the ability of the
      observers to use the two sequences to distinguish an intact cuff from a rotator
      cuff tear and to distinguish a partial-thickness cuff tear from an intact cuff or
      full-thickness tear. The results were then compared using Student's t test
      calculations. RESULTS: For distinguishing an intact cuff from a torn cuff, the
      sensitivity of the observers' interpretations was lower for the T2*-weighted
      images than for the conventional dual-echo T2-weighted images. The specificity
      also decreased with interpretation of the T2*-weighted images for one observer
      and was unchanged for the second observer. For distinguishing a partial-thickness
      cuff tear from a non-partial-thickness cuff tear (intact or full-thickness tear),
      the sensitivity and specificity of both observers decreased with interpretations
      of the T2*-weighted images when compared with the conventional dual-echo T2
      weighted images. The results did not reach statistical significance. CONCLUSION:
      In this small study evaluating the ability of observers to diagnose rotator cuff
      tears on oblique coronal MR images only, interpretations of T2*-weighted images
      tended to be less sensitive and specific than interpretations of standard dual
      echo T2-weighted images.

PMID- 9168718
TI  - Power Doppler sonography: use in measuring alterations in muscle blood volume
      after exercise.
AB  - OBJECTIVE: The purpose of this study was to show the ability of power Doppler
      sonography (PDS) to evaluate exercise-induced changes in muscle blood volume.
      SUBJECTS AND METHODS: We evaluated 20 biceps muscles with PDS in 10 healthy
      volunteers before and after they underwent a standardized exercise protocol.
      Intramuscular blood volume was qualitatively analyzed using a subjective scoring
      system to evaluate vascular conspicuity, comparing sonograms obtained before and
      after exercise. We also collected preliminary data on the quantification of
      estimated fractional moving blood volume (EFMBV) measured on sonograms obtained
      in eight biceps muscles of five volunteers. Assessment of significance was
      calculated using a Wilcoxon signed-rank correlation of significance. The
      stability of relative changes in EFMBV was also assessed with measurements
      performed at three different times in five healthy volunteers. RESULTS: With
      exercise, all 20 biceps muscles showed a significant subjective increase in
      apparent vascularity (p < .0005). Likewise, preliminary data on EFMBV showed
      significant increases (p < .01) between baseline and peak exercise values (mean,
      470%; range, 180-900%). CONCLUSION: PDS revealed marked increases in
      intramuscular vascular conspicuity after exercise. EFMBV provided a potentially
      useful parameter to document such increases quantitatively.

PMID- 9168719
TI  - Musculoskeletal involvement in cystic echinococcosis: report of eight cases and
      review of the literature.
AB  - OBJECTIVE: Our purpose was to describe the morphologic appearance of
      musculoskeletal lesions in patients with cystic echinococcosis shown by CT and MR
      imaging. CONCLUSION: Patients with musculoskeletal lesions of cystic
      echinococcosis typically have cystic structures in adjacent soft tissues. These
      cysts morphologically resemble abscesses, with peripheral uptake of contrast
      medium and variable signal intensities on T1-weighted MR images. The absence of
      calcifications or endovesicular daughter cysts does not exclude the diagnosis of
      cystic echinococcosis.

PMID- 9168720
TI  - Bronchial dilatation in patients with HIV infection: CT assessment and
      correlation with pulmonary function tests and findings at bronchoalveolar lavage.
AB  - OBJECTIVE: Symptoms of airway disease occur in patients infected with HIV, and
      bronchiectasis has been reported in patients with AIDS. We evaluated thin-section
      thoracic CT scans in HIV-positive individuals for bronchial dilatation and
      correlated imaging findings with pulmonary function abnormalities and findings at
      bronchoalveolar lavage (BAL). SUBJECTS AND METHODS: Sixty-one subjects, 50 of
      whom were HIV-positive and 11 of whom were HIV-negative, underwent thin-section
      CT, BAL, and pulmonary function tests. Two radiologists evaluated the CT scans on
      two separate occasions for bronchial dilatation in each lobe. BAL and pulmonary
      function test data in the subjects with bronchial dilatation were compared with
      such data in subjects with normal bronchi seen on CT scans. RESULTS: Eighteen of
      the 50 HIV-positive subjects and none of the HIV-negative subjects had bronchial
      dilatation revealed by CT. Subjects with bronchial dilatation revealed by CT had
      significantly higher BAL neutrophil counts (p = .014) and significantly lower
      diffusing capacity (p = .003) than did subjects with normal bronchi revealed by
      CT. CONCLUSION: Bronchial dilatation is commonly revealed by CT scans of HIV
      positive individuals. The association of elevated levels of BAL neutrophils and
      decreased diffusing capacity with bronchial dilatation that we found in this
      study suggests that the neutrophil may be associated with airway damage and lung
      destruction in patients who are infected with HIV.

PMID- 9168721
TI  - Pulmonary mucormycosis: radiologic findings in 32 cases.
AB  - OBJECTIVE: The purpose of this study was to characterize the radiologic
      manifestations of pulmonary mucormycosis with clinical and pathologic
      correlation. MATERIALS AND METHODS: Clinical records, pathology reports, chest
      radiographs, and CT scans of 32 cases of pathologically proven pulmonary
      mucormycosis were retrospectively reviewed. RESULTS: The study group included 20
      males and 12 females with a mean age of 47 years old. Clinical data were
      available for 29 patients. Signs and symptoms included fever (n = 23), cough (n =
      21), bloody sputum (n = 9), dyspnea (n = 7), and chest pain (n = 6). Four
      patients were asymptomatic. Most patients were either immunocompromised (n = 20)
      or had diabetes mellitus (n = 9). Sputum or bronchoalveolar lavage cultures
      showed no growth in 17 of 18 cases. Diagnoses were confirmed at surgery or
      autopsy in all cases. Abnormalities seen on chest radiographs included lobar (n =
      15) or multilobar (n = 6) consolidation, solitary (n = 7) or multiple (n = 1)
      masses, and solitary (n = 3) or multiple (n = 2) nodules. Cavitation was seen on
      chest radiographs in 13 patients, and intracavitary masses were seen in four.
      Associated radiographic findings included hilar (n = 3) or mediastinal (n = 3)
      adenopathy and unilateral (n = 6) or bilateral (n = 3) pleural effusion. CT in 19
      patients revealed these significant additional findings: splenic (n = 1) or renal
      (n = 1) involvement, bronchial occlusion (n = 1), extrapulmonary invasion (n =
      1), and pulmonary artery pseudoaneurysm (n = 1). CONCLUSION: In our study,
      pulmonary mucormycosis typically was manifested in immunocompromised or diabetic
      patients by consolidation on chest radiographs; cavitation was seen in 40% of
      patients. CT revealed significant unsuspected abnormalities in 26% of patients.
      Definitive diagnosis required pathologic demonstration of the organism in
      affected tissue because cultures from our patients rarely showed growth.

PMID- 9168722
TI  - Accuracy of MR angiography compared with radionuclide scanning in identifying the
      cause of pulmonary arterial hypertension.
AB  - OBJECTIVE: MR imaging has proven accurate in identifying patients with chronic
      thromboembolic pulmonary hypertension (CTEPH). However, we know of no attempt to
      distinguish patients with CTEPH from patients with other causes of pulmonary
      arterial hypertension (PAH). Primary pulmonary hypertension (PPH) is the disease
      most frequently confused with CTEPH. We examined patients with CTEPH or PPH and
      control subjects to identify MR imaging features that might distinguish CTEPH
      from PPH, to compare the accuracy of MR angiography (MRA) with that of
      radionuclide scanning, and to determine the cardiac and pulmonary vascular
      measurements in these groups. SUBJECTS AND METHODS: T1-weighted and two
      dimensional multiplanar spoiled gradient-recalled scans were obtained in 30
      patients with CTEPH who had undergone conventional pulmonary angiography, 10
      patients with PPH, and 13 control subjects with no known vascular disease.
      Ventilation-perfusion scans were available in all patients with CTEPH and in six
      of the 10 patients with PPH. The MR scans were assessed independently by two
      radiologists who evaluated the appearance of segmental vessels and noted the
      presence of mosaic perfusion. Cardiac chambers and pulmonary vessels were
      measured on T1-weighted spin-echo scans. RESULTS: The two radiologists used MR
      angiograms to reliably distinguish between patients with CTEPH and those with
      PPH. The accuracy of MR angiograms matched that of ventilation-perfusion scans
      (92%). On T1-weighted scans, the two radiologists used cardiac and pulmonary
      vascular measurements to distinguish patients with PAH from control subjects but
      failed to distinguish between patients with CTEPH and those with PPH. CONCLUSION:
      MRA is useful in distinguishing patients with CTEPH from those with PPH. In this
      population, MRA had an accuracy that was identical to that of radionuclide
      scanning. Vascular and cardiac measurements made on MR scans reliably identified
      patients with PAH but did not distinguish between patients with CTEPH and those
      with PPH.

PMID- 9168723
TI  - High-resolution CT findings of pulmonary sarcoidosis.

PMID- 9168724
TI  - Bronchiolitis obliterans due to neuroendocrine hyperplasia: high-resolution CT-
      pathologic correlation.

PMID- 9168725
TI  - Percutaneous ethanol injection therapy: use of a directable needle guide.

PMID- 9168726
TI  - Correlation between the grade of tumoral invasion and pain relief in patients
      with celiac ganglia block.

PMID- 9168727
TI  - Helical CT angiography for examination of living renal donors.
AB  - OBJECTIVE: This prospective study was intended to determine if helical CT
      arteriography plus conventional radiography is sufficiently accurate to replace
      and less costly than excretory urography and conventional renal arteriography,
      the techniques currently used to examine living renal donors. SUBJECTS AND
      METHODS: Patients underwent CT arteriography with a helical CT scanner.
      Conventional radiographs were obtained during the pyelographic phase to evaluate
      the urothelium. Findings on CT arteriograms were compared with findings on
      conventional arteriograms and at surgery. RESULTS: Of 57 patients who underwent
      CT arteriography, 46 also underwent conventional arteriography and 40 underwent
      surgery. For those 46 patients, we found agreement between results of CT
      arteriography and conventional arteriography in 89% of kidneys. For those 40
      patients, we found agreement between results of CT arteriography and findings at
      surgery in 90% of kidneys and agreement between results of conventional
      arteriography and findings at surgery in 87% of kidneys. Of the 57 patients, six
      (11%) had findings on CT angiograms that precluded further consideration for
      donation. CONCLUSION: Eight to ten percent of renal arteries are not seen on
      renal arteriograms when compared with findings at surgery. Our results indicate
      that CT arteriography is as accurate as conventional arteriography at revealing
      the number of vessels that perfuse and drain the kidneys and can replace
      conventional arteriography. Use of CT angiography plus conventional radiography
      instead of excretory urography and conventional arteriography can result in a 35
      50% reduction in cost of the imaging studies in potential renal donors.

PMID- 9168728
TI  - Renal vein thrombosis after vascular pedicle injury[clin conference].

PMID- 9168729
TI  - Comparison of two algorithms and their associated charges when evaluating adrenal
      masses in patients with malignancies.
AB  - OBJECTIVE: This study was performed to compare two proposed algorithms used when
      evaluating an adrenal mass discovered during staging evaluation of a patient with
      a known malignancy. Such evaluation was meant to lead to determination of the
      relative charges associated with each algorithm. SUBJECTS AND METHODS: Fifty-four
      patients with known malignancies who required evaluation of an adrenal mass
      underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital
      charges incurred for each procedure and any associated complications were
      normalized using national relative-value scale charges and conversion factors. A
      decision analysis was performed to compare the relative charges that would have
      been incurred if adrenal MR imaging had been performed in all patients, followed
      by CT-guided biopsy only in those patients with MR findings not diagnostic of
      adrenocortical adenoma, and the relative charges incurred if only CT-guided
      adrenal biopsy had been performed in every patient. RESULTS: Twenty-three (43%)
      of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The
      sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma
      were 94% and 100%, respectively. The charges incurred by performing MR imaging as
      the initial examination with subsequent CT-guided biopsy only in those patients
      with CSI findings not diagnostic of adenoma would have been similar to those
      incurred by first performing CT-guided adrenal biopsy in every patient.
      CONCLUSION: CSI is an accurate, noninvasive technique for evaluating adrenal
      masses in patients with cancer. If CT-guided biopsy is used only when CSI is not
      diagnostic of adrenocortical adenoma, the associated charges would be virtually
      the same as when CT-guided biopsy is performed as the first test in every
      patient. Moreover, biopsies could have been avoided in 54% of these patients.

PMID- 9168730
TI  - Stromal invasion by carcinoma of the cervix: assessment with dynamic MR imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate dynamic MR imaging in
      assessing the depth of stromal invasion by carcinoma of the cervix and to compare
      dynamic MR imaging with T2-weighted and contrast-enhanced T1-weighted MR imaging.
      SUBJECTS AND METHODS: Forty-one patients with carcinoma that was clinically
      considered to be confined to the cervix were examined with T2-weighted, dynamic,
      and contrast-enhanced T1-weighted MR imaging before surgery. We evaluated
      enhancement patterns of the cervix and tumor and assessed the degree of stromal
      invasion with MR imaging. The degree of stromal invasion was divided into two
      groups: superficial disease (no stromal invasion or invasion of < or = 3 mm) and
      deep invasion (> 3 mm of stromal invasion). Then we compared these MR findings
      with histologic results for the depth of stromal invasion. RESULTS: With dynamic
      MR imaging, cervical carcinoma with deep invasion was seen as a focal enhanced
      area in the early dynamic phase. The cervical epithelium and stroma enhanced less
      vividly. In distinguishing deep invasion from superficial disease, we found the
      accuracy of T2-weighted MR images, dynamic MR images, and contrast-enhanced T1
      weighted MR images to be 76%, 98%, and 63%, respectively. In particular, the
      detectability of 3.1-5.0 mm of stromal invasion with dynamic MR images was
      significantly higher than that with the other techniques: with T2-weighted MR
      images, we saw 3.1-5.0 mm of stromal invasion in 23% of patients; with dynamic MR
      images, in 92%; and with contrast-enhanced T1-weighted MR images, in none.
      Superficial disease was not revealed with any of the three MR techniques.
      CONCLUSION: We believe that dynamic MR imaging is superior to T2-weighted MR
      imaging and contrast-enhanced T1-weighted MR imaging when assessing the depth of
      invasion of cervical carcinoma.

PMID- 9168731
TI  - Fibrous pseudotumor of the epididymis.

PMID- 9168732
TI  - Correlation of findings on transvaginal sonography with serum CA 125 levels.
AB  - OBJECTIVE: This study was performed to correlate findings on transvaginal
      sonography with differential levels of serum CA 125. MATERIALS AND METHODS: The
      study population included 144 patients who underwent transvaginal sonography for
      suspected pelvic mass and in whom a serum CA 125 level was established as part of
      the diagnostic workup. Levels of less than 36 U/ml were considered nonelevated;
      levels equal to or greater than 36 U/ml but less than 50 U/ml were considered
      mildly elevated; levels of 50-100 U/ml, moderately elevated: and levels greater
      than 100 U/ml, markedly elevated. Seventy-eight patients had pathologically
      proven gynecologic disease. Sixty-six patients were followed up with serial
      sonograms; benign gynecologic disease was diagnosed in 39 of these patients. In
      the 5-year period included in the study, the patients followed up with serial
      sonograms were imaged an average of 2.6 times during 2.1 years. RESULTS:
      Transvaginal sonography had a sensitivity of 97%, a specificity of 97%, and an
      overall accuracy of 94% for correctly revealing pathologically proven gynecologic
      disease. Interpreters of the sonograms misdiagnosed no carcinomas, even in
      patients with nonelevated levels of CA 125. Likewise, no benign lesions were
      incorrectly interpreted as malignant, even in patients with markedly elevated
      levels of CA 125. When interpreters used CA 125 alone to evaluate for malignancy,
      those interpreters achieved a sensitivity of 85% and a specificity of 29% in all
      patients with levels of CA 125 greater than or equal to 36 U/ml. Also, the use of
      CA 125 alone to evaluate for malignancy had an even lower specificity (17%) in
      postmenopausal patients who had levels of CA 125 that exceeded 100 U/ml.
      CONCLUSION: Transvaginal sonography is a sensitive tool for diagnosing
      gynecologic disease in spite of misleadingly high or low levels of CA 125.
      Evaluation of levels of CA 125 should be discouraged before sonograms are
      obtained.

PMID- 9168733
TI  - A simple method for relative assessment of the sound propagation velocity in
      breast tumors: technique and diagnostic efficacy.
AB  - OBJECTIVE: The purpose of this study was to describe and evaluate a method for
      assessing the sound propagation velocity in breast tumors relative to the
      velocity in adjacent tissue. SUBJECTS AND METHODS: Sixty-six patients with
      palpable breast tumors were studied. The scanning plane was aligned so that it
      transected the tumor and depicted the front of a rib or the pleura-lung interface
      behind the tumor. This contour was evaluated for distortion, and the height of
      the distortion and the height of the tumor were used to calculate the relative
      sound propagation velocity. RESULTS: A posterior reference line was revealed
      behind 62 of 66 tumors. Of these 62 tumors, an elevation was seen behind 49
      tumors, and no distortion was seen behind 13 tumors. A depression was never
      observed. The median relative sound propagation velocity of 1.07 that was
      calculated in 42 carcinomas (range, 1.00-1.14) was insignificantly higher (p =
      .079) than the median relative sound propagation velocity of 1.04 obtained in 20
      fibroadenomas (range, 1.00-1.15). CONCLUSION: Although assessment of relative
      sound propagation velocity in breast tumors was successful, the relative
      velocities differed only insignificantly between benign and malignant lesions.

PMID- 9168734
TI  - Ruptured or intact: what can linear echoes within silicone breast implants tell
      us?
AB  - OBJECTIVE: During sonographic evaluation of silicone breast implants for possible
      rupture, we have frequently encountered several patterns of linear echoes within
      the implants. To our knowledge, the significance of this finding has not been
      established in the literature. The purpose of this study was to determine whether
      internal echoes are significant in predicting implant rupture. SUBJECTS AND
      METHODS: Thirty-three patients with 64 silicone implants were prospectively
      entered into a study that included gray-scale sonography of the implants and
      subsequent surgical removal. Echo patterns within the implants were
      retrospectively evaluated on hard-copy films and compared with the integrity of
      the implant at surgery. RESULTS: Three categories of internal echo patterns were
      identified: "thick linear echoes." "thin linear echoes," and "commas." One or
      more of these echo patterns were seen in 57 (89%) of the 64 implants. Thick
      linear echoes were seen in 23 (36%) of the 64 implants, thin linear echoes were
      seen in 33 (52%) of the 64 implants, and commas were seen in 47 (73%) of the 64
      implants. All echo patterns were seen in intact and ruptured implants with nearly
      equal frequency. We found no statistical significance for any echo pattern in
      predicting whether an implant was ruptured or intact. Of the 64 implants, four
      were entirely free of internal echoes. All four implants were intact. CONCLUSION:
      A variety of linear echoes can be seen in most silicone breast implants on gray
      scale sonography. The presence or absence of linear echoes is not useful in
      predicting implant rupture. Complete absence of internal echoes, while highly
      predictive of an intact implant, is infrequently seen.

PMID- 9168735
TI  - Mammography of breast carcinoma in women who have mutations of the breast cancer
      gene BRCA1: initial experience.
AB  - OBJECTIVE: We describe for the first time (to our knowledge) the mammographic
      appearance of breast cancer and breast density in carriers of the breast cancer
      gene BRCA1. CONCLUSION: The mammographic appearance of breast cancer in BRCA1
      carriers was similar to that in the general population. All mammographic
      densities were observed. Appropriate mammographic management of these extremely
      high-risk patients is yet to be determined.

PMID- 9168736
TI  - Accuracy of prenatal sonography for detecting circumvallate placenta.
AB  - OBJECTIVE: We determined the accuracy of prenatal sonography for detecting
      placental circumvallation, a placental abnormality associated with increased
      fetal morbidity and mortality. MATERIALS AND METHODS: We analyzed 62 healthy
      pregnant (range, 18-36 weeks) patients with focused placental sonography for
      detection of morphologic abnormality using the published criteria for
      circumvallate placenta (irregular edge, uplifted margin, or placental sheet or
      shelf). Placental marginal sonograms were taken at 30 degrees intervals around
      the entire placental margin. Five experienced sonologists who were unaware of the
      pathologic findings independently reviewed the placental images and graded the
      placentas from 1 (definitely normal) to 5 (definitely circumvallate). Receiver
      operating characteristic (ROC) curves and area under the ROC curve were
      calculated for each reader. Gross and microscopic pathology was used as the gold
      standard for all cases. RESULTS: In the 62 patients, sonography revealed 49
      normal placentas (79%), 12 partially circumvallate placentas (19%), and one
      completely circumvallate placenta (2%). ROC curves for the reviewers resulted in
      values for area under the curve ranging from .39 to .58. The sonologist who
      achieved the highest value for the area under the curve classified the 13 cases
      of proven circumvallation as one case of definite circumvallation, four cases as
      uncertain or equivocal, and eight cases as probably or definitely normal
      placentas. Of the normal placentas, 35% were graded as probably or definitely
      circumvallate by at least one sonologist. All sonologists misgraded the case of
      complete circumvallation as normal. CONCLUSION: Focused placental sonograms
      interpreted by experienced sonologists fail to detect the placental edge
      abnormality in most cases of circumvallation. In our study, 17 of 49 normal
      placentas were diagnosed as probably or definitely circumvallate by one or more
      observers. Our sonologists' interpretations of sonograms showed that complete
      circumvallation was difficult to assess. Although our study had a limited number
      of patients, the accuracy of sonography of the placenta for revealing
      circumvallation appears to be limited.

PMID- 9168737
TI  - The effect of oligohydramnios on detection of fetal anomalies with sonography.
AB  - OBJECTIVE: The sonographic examination of fetuses is generally thought to be
      compromised when oligohydramnios is present because of the subjective impression
      of less adequate visualization of fetal anatomy. The aim of this study was to
      evaluate the extent to which oligohydramnios limits our ability to detect major
      anomalies on sonograms. MATERIALS AND METHODS: Records from the University of
      California, San Francisco from March 4, 1989 through January 4, 1994, were
      reviewed to identify all cases of premature rupture of the membranes in patients
      who then underwent nontargeted sonography. Sonographic results in pregnancies
      with oligohydramnios and without oligohydramnios (control population) were
      compared. Follow-up was obtained from a perinatal database, autopsy reports, and
      medical records. RESULTS: We found 345 patients with a history of premature
      rupture of the membranes (175 with oligohydramnios, 170 without oligohydramnios).
      Gestational age of fetuses was 16-38 weeks. Major congenital anomalies, including
      hydronephrosis, ventriculomegaly, intestinal atresias, hydrops, congenital
      diaphragmatic hernia, skeletal dysplasias, cloacal malformations, and
      gastroschisis, were revealed on sonography in 13 of 175 pregnancies with
      oligohydramnios and in 17 of the 170 pregnancies in the control group. Major
      anomalies missed in the oligohydramnios group included cardiac anomalies, club
      foot, small ventral hernia, limb reduction defect, and anal atresia. Major
      anomalies missed in the control group were club foot, anal atresia, and
      tracheoesophageal fistula. All of the major anomalies missed in both groups were
      of the type that are known to be difficult to diagnose before birth and that are
      frequently missed on sonography. CONCLUSION: Although oligohydramnios
      subjectively degrades image resolution, sonography still reveals important fetal
      anatomic landmarks. Major anomalies can be detected on sonography even when the
      pregnancy has less than the normal amount of amniotic fluid.

PMID- 9168738
TI  - For patients with renal insufficiency, do low-osmolar iodinated contrast agents
      lessen the risk of nephrotoxicity, compared with high-osmolar agents?

PMID- 9168739
TI  - What role, if any, does nuclear medicine play in the evaluation of
      nonhypertensive renal artery stenosis?

PMID- 9168740
TI  - In the management of a patient with nonmalignant obstructive uropathy and known
      infection, isn't it safer and more prudent to attempt retrograde placement of a
      ureteral stent before percutaneous nephrostomy?

PMID- 9168741
TI  - On gradient-echo terminology and receiver operating characteristic methodology.

PMID- 9168742
TI  - Re: Osteoid osteoma after a fracture of the distal radius.

PMID- 9168743
TI  - CT angiography of aortoiliac disease with volumetric rendering technique.

PMID- 9168744
TI  - Re: Ionic versus nonionic contrast media.

PMID- 9168746
TI  - Re: The illustrated radiology report.

PMID- 9168745
TI  - Tumoral calcinosis caused by underlying renal disease.

PMID- 9168747
TI  - Slaves to expedience?

PMID- 9168748
TI  - Primary saphenous vein aneurysm presenting as a femoral hernia: radiographic
      findings.

PMID- 9168749
TI  - Oblique axial and oblique coronal MR imaging of the proximal femur.

PMID- 9168750
TI  - Anaphylactoid reaction to oral contrast agent.

PMID- 9168751
TI  - Superimposition of nipple shadows and real lesions.

PMID- 9168752
TI  - Gastric leiomyosarcoma: detection on plain chest radiograph.

PMID- 9168753
TI  - Villous tumors of the ampulla Vater.
AB  - Patients with villous tumors of the ampulla Vater usually present with jaundice,
      intermittent or constant, but may seek care for abdominal pain, intestinal
      hemorrhage, or pancreatitis. Because villous tumors may harbor carcinoma in 30 to
      50 per cent of cases, appropriate management may require radical resection. We
      have managed four patients with villous lesions of the ampulla Vater occurring in
      1981, 1992, 1993, and 1995. Three were villous (two with malignant change) and
      one was a villoglandular adenoma. Treatment consisted of local excision with
      reimplantation of the ducts in one patient, Whipple resection in two patients,
      and biliopancreatic bypass in one who had distant nodal metastases not resectable
      for cure. This patient died 18 months after operation of an unrelated disease,
      but the others were well at last follow-up. The presentation as well as the
      diagnostic and therapeutic considerations in the management of villous tumors of
      the ampulla Vater are discussed.

PMID- 9168754
TI  - Cholecystogastrocolonic fistula with intrahepatic abscess: a rare complication of
      biliary stone disease.
AB  - A 52-year-old woman exhibited both a cholecystogastrocolonic fistula and
      intrahepatic abscess. Biliary-enteric fistulas are unusual complications of
      gallstone disease, and multiple, complex fistulas are extremely uncommon. Hepatic
      abscesses are also unusual complications of gallstone disease. The combination of
      a complex biliary-enteric fistula and hepatic abscess arising from gallstone
      disease has not been reported. In our patient, surgery was prompted by the
      hepatic abscesses; the fistula was not recognized preoperatively. We elected to
      resect gallbladder, gastric antrum, and transverse colon en bloc with primary
      closure of the gastric defect and, because the colon had not been "prepped," we
      created a right transverse colostomy and left mucus fistula. Under ideal
      circumstances, the anatomy of biliary fistulas is characterized preoperatively
      and managed definitively with a single procedure.

PMID- 9168755
TI  - Retroperitoneal fibrosis: a report of complete colonic obstruction.
AB  - Idiopathic retroperitoneal fibrosis (RPF) is a disease entity rarely encountered
      by the general surgeon. In most cases, ureteral stricture is the underlying
      problem requiring lysis of fibrotic adhesions. However, infrequently, the
      gastrointestinal tract may become involved. The following report describes the
      complications of intestinal obstruction by RPF in one of our patients. The
      discussion then focuses on the need for early diagnosis and treatment of
      gastrointestinal invasion by RPF.

PMID- 9168756
TI  - Laparoscopic examination of the traumatized spleen with blood salvage for
      autotransfusion.
AB  - The management of splenic trauma presents a dilemma to the surgeon, who must
      weigh the risks of operative versus nonoperative management. Laparoscopy has been
      used increasingly for trauma cases to decrease the morbidity associated with
      standard laparotomy. Autotransfusion of the patient's shed blood has also become
      widespread to decrease the risks associated with transfusion. We describe the
      case of a 15-year-old male with blunt splenic trauma, in which laparoscopy was
      used to examine the spleen to ascertain the need for operative treatment, to look
      for other intra-abdominal injuries, and to salvage intraperitoneal blood for
      autotransfusion. In this case, laparoscopy determined that laparotomy would be
      nontherapeutic, and that autotransfusion could obviate the need for banked-blood
      transfusion.

PMID- 9168757
TI  - Metastatic head and neck cancer to the percutaneous endoscopic gastrostomy exit
      site: a case report and review of the literature.
AB  - Percutaneous endoscopic gastrostomy (PEG) is a relatively safe procedure and is
      an important supportive treatment adjunct for patients with head and neck cancer.
      We report a case in which squamous cell carcinoma of the larynx implanted at a
      PEG exit site. This was resected for cure. In this case, and in five others
      reviewed in the literature, the PEG placement method was the "pull" technique. It
      is unknown whether other methods of PEG placement may reduce metastatic implants
      at the PEG exit site, but the possibility of this complication must be
      considered.

PMID- 9168758
TI  - Brachial plexus injury due to compression: an alternate mechanism of injury: case
      report and review of the literature.
AB  - We present a case of a brachial plexus injury due to compression of the nerves
      from a traumatic hematoma, with no associated bone or vascular injury. The
      paralysis in this case was not evident for 48 hours after the initial injury,
      implying that the brachial plexus was not damaged directly. Electromyograms
      documenting brachial plexopathy were obtained. The mechanism of injury in this
      case is different from the usual mechanisms of injury in brachial plexus trauma.
      The majority of brachial plexus injuries are associated with multisystem trauma.
      The mechanism of injury to the brachial plexus is either from extreme traction on
      the nerves or direct impact. Downward traction generally results in lesions in
      the upper cervical nerve roots, whereas upward traction results in lesions of the
      lower cervical nerve roots, C8 and T1. The usual symptoms of brachial plexus
      injuries include paralysis of the shoulder, arm, and/or hand with parasthesias
      and altered sensation. Temperature and color of the limb may be altered because
      of damage to the autonomic nervous system. The treatment of brachial plexus
      injuries varies depending on the mechanism and the time the injury is discovered
      in relation to the inciting trauma. Current treatment includes assessing function
      with physical examination, preoperative electromyogram, and then repair of viable
      nerve roots and associated vascular injuries.

PMID- 9168759
TI  - Management of splenic trauma at a rural, Level I trauma center.
AB  - The spleen is the most commonly injured organ in blunt abdominal trauma. There
      remains much controversy in the diagnosis and management of the injured spleen,
      with a recent trend toward nonoperative management. A 5-year period was reviewed
      at a rural, Level I trauma center to address issues of operative versus
      nonoperative management. During this time period, there were 136 patients
      identified as having trauma to the spleen. Most (95%) were the result of blunt
      trauma, and a majority of these were from motor vehicle accidents. Computed
      tomography was the most frequent method of diagnosis. Approximately half of the
      patients underwent immediate operative intervention. Of those initially observed,
      10 patients (16%) eventually were operated on. Most of the cases were due to
      underestimation of the severity of the splenic injury, and most received blood
      transfusion. This experience suggests that observation for splenic trauma is
      appropriate in many cases, as long as the surgeon is certain the spleen is not
      actively bleeding and the patient will not require blood transfusion.

PMID- 9168760
TI  - Delayed presentation of popliteal artery pseudoaneurysm following blunt trauma.
AB  - Popliteal artery pseudoaneurysms are not uncommon. They may result from
      penetrating or blunt trauma, arterial reconstructive surgery, invasive diagnostic
      or surgical orthopedic procedures, and perigenicular neoplasia. We report two
      patients with popliteal artery pseudoaneurysm diagnosed 3 months and 3 weeks,
      respectively, after blunt trauma. These two patients as well as many patients
      reported in the literature had palpable distal pulses and no obvious clinical
      signs of arterial injury following various forms of trauma. Arteriography in
      these circumstances is usually abandoned because of the low yield and the
      possible risk of complications. However, as we illustrate in this report,
      noninvasive diagnostic modalities such as duplex ultrasound and magnetic
      resonance arteriography are both safe and accurate for early detection of
      popliteal artery pseudoaneurysm. Once diagnosed, standard vascular reconstruction
      should be performed to prevent potential complications.

PMID- 9168761
TI  - A new standard of care: administration of preoperative antibiotics in the
      operating room.
AB  - Surgical site infections increase total hospital expenses and extend the length
      of hospital stay. Properly administered antibiotics are successful in minimizing
      postoperative subcutaneous wound infection secondary to perioperative bacterial
      contamination at the surgical site and are effective in most clean-contaminated
      surgical procedures. It is imperative that therapeutic levels of antibiotics be
      present during the time when the wound is open to maximize their effect to
      prevent the development of surgical wound infections. Only 32 per cent of 97
      patients sampled from 1992 to 1994 at the Louisville Veterans Affairs Medical
      Center were administered preoperative antibiotics within 1 hour prior to surgical
      incision. Changing the responsibility for preoperative antibiotic administration
      from ward or holding room nurses to the anesthesiologist in the operating room
      rendered such antibiotics delivered closer to the induction of anesthesia and
      subsequent incision. Eighty-eight per cent of 220 patients sampled in 1995 had
      antibiotics administered within 1 hour of incision. This change in institutional
      policy of antibiotic administration maximizes the likelihood of appropriate
      antibiotic tissue levels and thereby their potential efficacy. Routine
      prophylaxis should be administered as close to the time of induction of
      anesthesia as possible to provide the best chance for appropriate tissue levels
      above the minimum inhibitory concentration for potential bacterial contamination.

PMID- 9168762
TI  - Pneumoretroperitoneum secondary to an open reduction and internal fixation of a
      femoral fracture: case report.
AB  - We present a case of pneumoretroperitoneum detected on computed tomography that
      resulted from open reduction and internal fixation of a femoral fracture.
      Retroperitoneal air has many etiologies. These range from the clinically
      insignificant to the potentially catastrophic, if not recognized promptly. We
      present a case of retroperitoneal air secondary to open reduction and internal
      fixation of a femoral fracture. To our knowledge, this association has not
      previously been described.

PMID- 9168763
TI  - Cholecystectomy following the introduction of laparoscopy: more, but for the same
      indication.
AB  - To assess whether indications for cholecystectomy might have changed after the
      introduction of laparoscopic cholecystectomy (LC), the data from patients
      undergoing cholecystectomy at the University of South Alabama Medical Center
      during 1988 (before LC) and 1993 (after the introduction of LC) were
      retrospectively analyzed and compared. In 1993, the number of patients undergoing
      cholecystectomy for gallstone-related disease was 18 per cent higher than in 1988
      (87 vs 103, 1.4 per cent of all noncardiac operations vs 2.7 per cent, Chi
      square; P = 0.003). There was no difference in the mean Preoperative Severity
      Index, a quantitative evaluation of symptom complex, preoperative laboratory
      evaluation, and radiological findings. Besides obesity, there were also no
      differences between the groups in associated comorbidities that might affect the
      decision to proceed with operation. Furthermore, pathologic findings, including
      the distribution of patients with gallstone pancreatitis, symptomatic
      cholelithiasis, chronic cholecystitis, and acute cholecystitis, were similar in
      both groups. The indications for cholecystectomy did not broaden after the
      introduction of LC, but rather, more patients with similar indications are
      undergoing cholecystectomy now, as compared with the pre-laparoscopic era.

PMID- 9168764
TI  - Solitary breast metastasis to the ampulla and distal common bile duct.
AB  - The indications for pancreaticoduodenectomy have continued to expand over the
      past 10 to 15 years. This is in large part due to improved diagnostic studies,
      endoscopic retrograde cholangiopancreaticogram and computed tomography, and
      decreases in hospital perioperative morbidity and mortality. One third of breast
      cancer patients will develop metastatic disease usually to the liver, lung, or
      bone (World J Surg 1994;18:98-111). However, the presentation of painless
      jaundice due to a single metastatic lesion to the distal common bile duct from
      ductal adenocarcinoma of the breast is extremely rare. In this case report and
      review of the literature, we discuss the indications and emerging evidence that
      pancreaticoduodenectomies can now be performed for localized metastatic disease.

PMID- 9168765
TI  - Massive pulmonary embolus after surgery for renal cell carcinoma extending into
      the inferior vena cava: a case report.
AB  - Fatal massive pulmonary embolization following removal of an intracaval renal
      cell carcinoma was encountered. This case teaches that vena cava interruption
      should be considered as part of the perioperative management of patients with
      renal cell carcinoma tumor thrombus extending into the inferior vena cava.

PMID- 9168766
TI  - Cholestasis in patients with acquired immunodeficiency syndrome: a surgeon's
      perspective.
AB  - Cholestasis is a common finding in patients with acquired immunodeficiency
      syndrome. The underlying causes may be related to intrahepatic processes,
      cholecystitis, papillary stenosis, or sclerosing cholangitis. Published reports
      of hepatobiliary diseases in patients with acquired immunodeficiency syndrome are
      reviewed. The etiological factors are considered, and available therapeutic
      approaches are discussed. Hepatic causes of cholestasis indicate poor prognosis,
      and effective treatments are not yet available. Cholecystitis, often acalculous
      in origin, remains a surgical disease. Endoscopic sphincterotomy appears to give
      good results in the treatment of papillary stenosis. Although a standard approach
      to sclerosing cholangitis has not been established, a trial of appropriate
      antibiotics may be beneficial. Frequently, the cause of cholestasis is
      multifactorial in these patients; thus, a coherent therapeutic approach is
      essential for optimal clinical results.

PMID- 9168767
TI  - How many antibiotics are necessary to treat abdominal trauma victims?
AB  - We wanted to determine the value of single-versus multiple-antibiotic treatment
      in cases of penetrating abdominal trauma. Of 357 patients entered into a
      prospective, randomized, examiner-blinded study, 291 met all protocol criteria;
      101 of these patients received cefoperazone alone, 95 were given ceftriaxone with
      metronidazole, and 95 were placed on metronidazole, gentamicin, and ampicillin.
      Aerobic and anaerobic bacterial cultures were obtained upon opening and closing
      the peritoneum. The three groups were found to be similar upon evaluation of key
      parameters, such as the median number of febrile days, morbidity, incisional
      wound infection, intra-abdominal abscess, septicemia, other infections, hospital
      stay, and death. Fifteen of 291 (5%) patients had infectious complications, and
      12 (4.1%) developed noninfectious complications. There were six (2.1%) deaths,
      two in each antibiotic group. Noninfectious complications occurred more
      frequently in the triple-antibiotic group, which was statistically significant (P
      = 0.013). There were no therapeutic failures, and therefore, the routine usage of
      additional antibiotics to cover for enterococcus needs justification.

PMID- 9168768
TI  - Concomitant laparoscopic cholecystectomy and splenectomy for surgical management
      of hereditary spherocytosis.
AB  - Laparoscopic splenectomy is rapidly becoming a common treatment modality in the
      surgical management of hematological processes involving the spleen. Hereditary
      spherocytosis is the most common red blood cell membrane disorder, and its
      diagnosis is often associated with hemolytic crisis and premature cholelithiasis.
      This condition has not been successfully treated laparoscopically until recently,
      and to our knowledge, the technique of concomitant laparoscopic splenectomy and
      cholecystectomy described here is the first reported in U.S. literature. Our
      patients, a 16-year-old 5-foot 3-inch-tall 90 pound emaciated albino, presented
      with cholelithiasis, splenomegaly, and anemia. Because of persistent anemia and
      gastrointestinal symptoms, the patient underwent laparoscopic cholecystectomy and
      splenectomy. The cholecystectomy was performed in a standard laparoscopic
      fashion. An additional 12-mm trocar was utilized for takedown of the spleen. The
      umbilical incision was extended to 4.5 cm, and the spleen was extracted manually.
      Total operative time was 12 hours. Examination demonstrated a 15 x 10 x 5-cm
      spleen, which weighed 350 grams. The gallbladder microscopically showed
      cholecystitis and had several stones. In conclusion, we present a combined
      laparoscopic cholecystectomy and splenectomy for hereditary spherocytosis
      associated with splenomegaly, cholelithiasis, and cholecystitis.

PMID- 9168769
TI  - Thoracoscopic vagotomy as a safe adjunct to remedial gastric surgery.
AB  - Patients who have had prior subdiaphragmatic dissection with an incomplete
      vagotomy or Nissen fundoplication present added challenges when they require
      vagotomy and gastric resection. In this setting, thoracoscopic vagotomy offers
      significant advantages. A second attempt at vagotomy in a previously dissected
      field can be prolonged and frustrating. In addition to these concerns, repeat
      dissection can also lead to failure to find the vagal trunks, perforation of the
      esophagus, hemorrhage, and/or splenic injury. In our experience, three patients
      requiring gastrectomy or resection of a marginal ulcer have undergone
      thoracoscopic vagotomy at the time of transabdominal gastric surgery. The
      thoracoscopic approach avoided either a thoracoabdominal incision or combined
      thoracic and abdominal incisions while allowing dissection of the vagal trunks to
      be performed in normal tissue planes. The minimally invasive approach afforded
      decreased postoperative pain and excellent clinical results. Thoracoscopic
      vagotomy offers a welcome alternative to re-exploration of a previously dissected
      distal esophagus in search of vagal trunks, especially when they have been missed
      at the time of the first operation. Further application of this approach is
      recommended.

PMID- 9168770
TI  - Complications of epidural infusions for analgesia in postoperative and trauma
      patients.
AB  - Few studies compare complications of continuous and bolus epidural analgesia.
      Ninety-eight postoperative and trauma patients receiving epidural infusions over
      15 months were retrospectively studied. Continuous epidural analgesia was used
      for pain management in 60 patients (61%). Bolus epidural analgesia was
      administered to 38 patients (39%). Sixty patients reported 98 complications.
      Sixty-eight per cent of complications occurred in patients receiving continuous
      infusions. For the continuous infusions, motor blockade (18%), nausea/vomiting,
      (18%), and catheter leaks (12%) were the most common complications. For bolus
      infusions, nausea/vomiting (25%), mental status changes (21%), and erythema at
      placement site (13%) were encountered. Continuous infusions were associated with
      an increased incidence of complications compared with bolus infusions (P < 0.05).
      Patients undergoing abdominal surgery had an increased incidence of complications
      compared with other patients (P < 0.05). Epidural catheters are safe and
      effective for pain management, but they are not without risk. Hemodynamic
      stability and pulmonary status should be considered when evaluating patients.

PMID- 9168771
TI  - The role of preoperative factor V Leiden screening in different geographic
      populations.
AB  - Patients harboring a specific mutation in the coagulation factor V gene have been
      identified as being at significantly increased risk for venous thrombosis. A
      simple genetic test that identifies carriers of this mutation (the factor V
      Leiden allele) is available and may have utility in various clinical settings,
      including preoperative risk assessment for thromboembolic complications. In this
      regard, it is generally agreed that prospective studies addressing the role of
      preoperative factor V Leiden mutational analysis are needed to clearly define the
      clinical prognostic/diagnostic significance of the presence of this mutation in
      surgical patients. This report questions the role that population dynamics
      (genetic and environmental backgrounds of individual populations) plays in the
      analysis of factor V genotypic data in relation to postsurgical thromboembolic
      complications. We have determined that the frequency of individuals carrying the
      factor V Leiden allele is 7.9 per cent for our South Central Pennsylvania
      population (395 wild type, 32 heterozygotes, 2 homozygotes) using a polymerase
      chain reaction-restriction fragment length polymorphism technique that
      specifically detects the factor V Leiden mutation. This baseline population
      information is useful from both a clinical and a basic science viewpoint.
      However, considering the various unknown genetic and environmental differences
      between geographically distinct populations, the significance of this result, in
      terms of clinical management of our surgical patients, is yet to be determined.

PMID- 9168772
TI  - Long-term quality of life outcome after treatment for Helicobacter pylori gastric
      infection.
AB  - Helicobacter pylori has been associated with a number of upper gastrointestinal
      diseases. Treatment directed toward H. pylori promotes ulcer healing and
      decreases ulcer recurrence. This study reports a longer-term quality of life
      follow-up in a group of patients treated for H. pylori. Thirty patients who were
      treated for upper gastrointestinal symptoms at least 2 years (median 32 months)
      prior to the initiation of this study had the Gastrointestinal Symptom Rating
      Scale questionnaire mailed to them. 19 patients responded. This scale measures
      abdominal pain, heartburn, acid regurgitation, sucking sensations in the upper
      abdomen, nausea and vomiting, borborygmus, abdominal distention, and belching.
      Three groups of patients were studied: symptomatic patients without H. pylori
      infection, symptomatic patients with H. pylori infection and successful
      eradication, and symptomatic patients with H. pylori infections without
      eradication. The median symptom scores for each group were no more than 1.5.
      However, there were no statistically significant differences among these three
      groups in any of the eight items measured by the Gastrointestinal Symptom Rating
      Scale. The sample size of this study was sufficient to detect a difference
      between groups of 1.6. Patients treated for H. pylori have no to occasional upper
      gastrointestinal symptoms in more than 2 years' follow-up. There appears to be no
      difference in patients treated for the infection and those without the infection.

PMID- 9168773
TI  - Abdominal compartment syndrome: case reports and implications for management in
      critically ill patients.
AB  - Five cases are reviewed in which intra-abdominal pressures were used to decide
      whether critically ill patients would undergo exploratory laparotomy. This is a
      retrospective case series of a convenience sample of five critically ill,
      postoperative patients with a variety of underlying illnesses admitted to a
      surgical intensive care unit in a university hospital. Intra-abdominal
      compartment pressures were measured using the indirect method of urinary bladder
      pressure. In patients with signs of abdominal compartment syndrome, intra
      abdominal pressures were measured. The pressures were measured every 6 hours
      until the signs had resolved or the patient was taken for exploratory laparotomy.
      All patients had Foley catheters. The drainage tubing to the catheters was
      clamped after the infusion of 200 cc of sterile water. An 18-gauge needle was
      inserted into the sampling port of the drainage tubing proximal to the clamp, and
      the needle was connected to a pressure transducer. An elevated abdominal
      compartment pressure was considered at greater than 25 mm Hg. The case series
      were reviewed to determine in critically ill patients whether intra-abdominal
      pressures could assist in deciding which patients required emergent exploratory
      laparotomy. The patients underwent frequent venous and arterial blood gas and
      hemodynamic measurements. If the clinical course of the patients worsened as
      indicated by requiring additional pressors, ventilator support and/or oliguria
      intra-abdominal pressures were measured every 6 hours. The five patients whose
      intra-abdominal pressures were elevated were taken for exploratory laparotomy.
      Four patients were found to have urgent surgical conditions. Intra-abdominal
      pressures can be used to help decide which patients can be aggressively supported
      and observed and which patients need re-exploration. At exploration the patient
      may be found to have necrotic large or small intestines instead of the classical
      abdominal compartment syndrome findings of ascites, hematoma, and bowel wall
      edema. In symptomatic patients with abdominal compartment pressures greater than
      30 mm Hg, the patient should be taken for exploration. It is not necessary to
      perform any further diagnostic tests before exploring the patient.

PMID- 9168774
TI  - Modifications of Bishop's method for pediatric gastrostomy closure.
AB  - In 1981, H.C. Bishop described a simple and effective method for pediatric
      gastrostomy closure. We have modified this approach in order to simplify and
      shorten the period of postoperative management.

PMID- 9168775
TI  - Lincoln's last hours.

PMID- 9168776
TI  - Re: Safe and effective early postoperative feeding and hospital discharge after
      open colon resection.

PMID- 9168777
TI  - Compartment-selective sensitivity of cardiovascular morphogenesis to combinations
      of retinoic acid receptor gene mutations.
AB  - Several aspects of normal cardiovascular development require signaling by the
      vitamin A metabolite retinoic acid. We have previously established germ-line
      mutations in mice in the genes that encode the RAR alpha 1, RAR beta, and RXR
      alpha retinoic acid receptors as a means of studying the function of these
      receptors in vivo. Although mutation of RXR alpha results in fetal ventricular
      defects, the RAR alpha 1 and RAR beta mutations are apparently nonphenotypic in
      the heart and elsewhere. In this study, we have established and analyzed
      combinations of these receptor gene mutations. Malformations of the ventricular
      chamber (chamber hypoplasia and muscular ventricular septal defects), conotruncus
      (double-outlet right ventricle, transposition, and membranous ventricular septal
      defects), aortic sac (persistent truncus arteriosus and aorticopulmonary window),
      and aortic arch-derived arteries were recovered in various combinations of the
      RAR alpha 1, RAR beta, and RXR alpha gene mutations. Depending on the combination
      of receptor mutations, selective defects were obtained in specific cardiovascular
      compartments, suggestive of differential expression or function of each receptor
      within domains of the developing heart.

PMID- 9168778
TI  - Changes in cell-to-cell electrical coupling associated with left ventricular
      hypertrophy.
AB  - The impedance to current flow in the intracellular compartment of guinea pig left
      ventricular myocardium was measured at 20 degrees C and 37 degrees C using tissue
      from hypertrophied hearts subjected to aortic constriction. Alternating current
      of varying frequency was passed longitudinally along myocardial preparations,
      which revealed two time constants: one attributed to the surface membrane at the
      ends of the preparation and a second lying in the intracellular pathway. The
      longitudinal impedance was quantitatively analyzed in terms of a parallel
      intracellular and extracellular pathway; the former had two series components,
      one attributable to the sarcoplasm and the other to the low-resistance junctions
      between adjacent cells. This interpretation was consistent (1) with control
      experiments using n-heptanol, which increased the component attributed to
      intercellular junctions but not sarcoplasmic resistivity, and (2) with
      suspensions of isolated myocytes, which yielded a similar value for the
      sarcoplasmic resistivity. Aortic constriction increased the heart weight-to-body
      weight ratio of experimental animals from a mean value of 3.10 +/- 0.28 to 5.05
      +/- 0.83 g/kg after 50 days of constriction and 5.60 +/- 0.95 g/kg after 150 days
      of constriction. An increase of heart weight-to-body weight ratio at 150 days of
      constriction was associated with an increased intracellular resistivity, which
      could be attributed solely to an increase of the junctional resistance between
      adjacent cells by approximately 44% at 20 degrees C and 140% at 37 degrees C; the
      sarcoplasmic resistivity was unchanged. The results are discussed in terms of
      altered conduction in hypertrophied myocardium as a possible basis for
      arrhythmias in this tissue.

PMID- 9168779
TI  - Outward K+ current densities and Kv1.5 expression are reduced in chronic human
      atrial fibrillation.
AB  - Chronic atrial fibrillation is associated with a shortening of the atrial action
      potential duration and atrial refractory period. To test the hypothesis that
      these changes are mediated by changes in the density of specific atrial K+
      currents, we compared the density of K+ currents in left and right atrial
      myocytes and the density of delayed rectifier K+ channel alpha-subunit proteins
      (Kv1.5 and Kv2.1) in left and right atrial appendages from patients (n = 28) in
      normal sinus rhythm with those from patients (n = 15) in chronic atrial
      fibrillation (AF). Contrary to our expectations, nystatin-perforated patch
      recordings of whole-cell K+ currents revealed significant reductions in both the
      inactivating (ITO) and sustained (IKsus) outward K+ current densities in left and
      right atrial myocytes isolated from patients in chronic AF, relative to the ITO
      and IKsus densities in myocytes isolated from patients in normal sinus rhythm.
      Quantitative Western blot analysis revealed that although there was no change in
      the expression of the Kv2.1 protein, the expression of Kv1.5 protein was reduced
      by > 50% in both the left and the right atrial appendages of AF patients. The
      finding that Kv1.5 expression is reduced in parallel with the reduction in
      delayed rectifier K+ current density is consistent with recent suggestions that
      Kv1.5 underlies the major component of the delayed rectifier K+ current in human
      atrial myocytes, the ultrarapid delayed rectifier K+ current, IKur. The
      unexpected finding of reduced voltage-gated outward K+ current densities in
      atrial myocytes from AF patients demonstrates the need to further examine the
      details of the electrophysiological remodeling that occurs during AF to enable
      more effective and safer therapeutic strategies to be developed.

PMID- 9168780
TI  - Rapid inactivation determines the rectification and [K+]o dependence of the rapid
      component of the delayed rectifier K+ current in cardiac cells.
AB  - Two characteristic features of the rapid component of the cardiac delayed
      rectifier current (IKr) are prominent inward rectification and an unexpected
      reduction in activating current with decreased [K+]o. Similar features are
      observed with heterologous expression of HERG, the gene thought to encode the
      channel carrying IKr, moreover, recent studies indicate that the mechanism
      underlying rectification of HERG current is the inactivation that channels
      rapidly undergo during depolarizing pulses. The present studies were designed to
      determine the mechanism of IKr rectification and [K+]o sensitivity in the mouse
      atrial myocyte cell line, AT-1 cells. Reducing [Mg2+]i to 0, which reverses
      inward rectification of some K+ channels, did not alter IKr current-voltage
      relationships, although it did decrease sensitivity to the IKr blockers
      dofetilide and quinidine 2- to 5-fold. To determine the presence and extent of
      fast inactivation of IKr in AT-1 cells, a brief hyperpolarizing pulse (20 ms to 
      120 mV) was applied during long depolarizations. Immediately after this pulse, a
      very large outward current that decayed rapidly to the previous activating
      current baseline was observed. This outward current component was blocked by the
      IKr-specific inhibitor dofetilide, indicating that it represented recovery from
      fast inactivation during the hyperpolarizing step, with fast reinactivation
      during the return to depolarized potential. With removal of inactivation using
      this approach, current-voltage relationships for IKr ([K+]o, 1 to 20 mmol/L) were
      linar and reversed close to the predicted Nernst potential for K+. In addition,
      decreased [K+]o decreased the time constants for open-->inactivated and
      inactivated-->open transitions. Thus, in these cardiac myocytes, as with
      heterologously expressed HERG, IKr undergoes fast inactivation that determines
      its characteristic inward rectification. These studies demonstrate that the
      mechanism underlying decreased activating current observed at low [K+]o is more
      extensive fast inactivation.

PMID- 9168781
TI  - Ca2+ as a mediator of ischemic preconditioning.
AB  - We tested the hypothesis that elevation of [Ca2+]i during ischemic
      preconditioning (IPC) stimulates protein kinase C (PKC), which confers the
      protection against the ischemic injury. Langendorff-perfused rat hearts were
      subjected to 40-minute global ischemia followed by 30-minute reperfusion (I/R).
      In preconditioned groups, hearts were subjected to either IPC, consisting of 5
      minute global ischemia and 10-minute reperfusion, or high-Ca2+ preconditioning
      (HCPC), ie, the 5-minute perfusion of higher Ca2+ perfusate (2.3 mmol/L Ca2+)
      followed by 10-minute perfusion of normal perfusate (1.8 mmol/L Ca2+), and then
      were subjected to I/R. A significant functional recovery and decreased lactate
      dehydrogenase release were observed in HCPC and IPC hearts compared with ischemic
      control hearts. ATP contents of preconditioned hearts were significantly higher
      than those of the ischemic control hearts. The cell structure in preconditioned
      hearts was preserved better than that in the ischemic control hearts.
      Furthermore, the activation and translocation of PKC from cytoplasm to sarcolemma
      were observed in the preconditioned hearts. Verapamil administered during IPC
      significantly attenuated the salutary effects of IPC. Administration of
      chelerythrine, a specific PKC inhibitor, completely abolished the HCPC- and IPC
      induced cardioprotection. The translocation of PKC by IPC was blocked by
      verapamil or chelerythrine. Immunohistochemical study using rabbit polyclonal
      antibody against PKC isoforms indicated that stress induced by IPC or HCPC evoked
      the translocation of PKC alpha and PKC delta to the cell membrane. Translocation
      of PKC isoforms was attenuated by the treatment with verapamil or chelerythrine.
      These results demonstrate that (1) a transient increase in [Ca2+]i during IPC is
      an important trigger for the activation of PKC, which is responsible for
      cardioprotection; (2) the elevation of [Ca2+]i during IPC, at least partly,
      resulted from Ca2+ entry via voltage-dependent Ca2+ channel; and (3) activation
      and translocation of PKC alpha and PKC delta occur during IPC and HCPC and may be
      important in preconditioning.

PMID- 9168782
TI  - Selective activation of A3 adenosine receptors with N6-(3-iodobenzyl)adenosine-5'
      N-methyluronamide protects against myocardial stunning and infarction without
      hemodynamic changes in conscious rabbits.
AB  - To examine the cardioprotective role of A3 adenosine receptors during myocardial
      ischemia/reperfusion injury, we tested the effect of N6-(3-iodobenzyl)adenosine
      5'-N-methyluronamide (IB-MECA), a potent and selective A3 adenosine receptor
      agonist, in models of myocardial stunning and infarction in chronically
      instrumented conscious rabbits. In phase I (studies of myocardial stunning),
      rabbits were subjected to six 4-minute coronary occlusions, each separated by 4
      minute reperfusion periods, after which the recovery of systolic wall thickening
      was measured (ultrasonic crystals). In phase II (studies of myocardial
      infarction), rabbits were subjected to a 30-minute coronary occlusion followed by
      3 days of reperfusion. In both phases, IB-MECA was administered as an intravenous
      bolus (100 micrograms/kg) 10 minutes before the first coronary occlusion. This
      dose of IB-MECA was determined in pilot studies to have no effect on heart rate,
      arterial blood pressure, or plasma histamine concentration in rabbits. In phase
      I, IB-MECA markedly improved the recovery of wall thickening after the six
      occlusion/reperfusion cycles, and this effect was sustained throughout the 5-hour
      observation period; the total deficit of wall thickening (a measure of the
      overall severity of myocardial stunning) was reduced by 68% (control, 129 +/- 16
      arbitrary units, n = 7; IB-MECA, 41 +/- 6 arbitrary units, n = 6; P < .01). The
      protective effects of IB-MECA against stunning were completely blocked by
      pretreatment with the nonselective adenosine receptor antagonist 8-p-sulfophenyl
      theophylline or the specific protein kinase C inhibitor chelerythrine. In phase
      II, IB-MECA reduced myocardial infarct size by 61%; infarct size (tetrazolium
      staining) was 41 +/- 4% of the risk region in control animals (n = 8) and 16 +/-
      6% in IB-MECA-treated animals (n = 8, P < .01). These results demonstrate that in
      conscious rabbits the A3 adenosine receptor agonist IB-MECA confers a powerful
      protection against both reversible (stunning) and irreversible (infarction)
      injury during acute myocardial ischemia and reperfusion by a protein kinase C
      mediated pathway, suggesting that selective activation of A3 receptors is an
      effective means of protecting the ischemic myocardium without hemodynamic
      changes.

PMID- 9168783
TI  - Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis
      and surface expression.
AB  - Leukocyte binding to the endothelium is one of the earliest events in the
      occurrence of atherosclerosis. Leukocyte adhesion molecules involved in this
      process have not been definitely identified. We have found that treatment of
      human aortic endothelial cells (HAECs) with minimally modified low-density
      lipoprotein (MM-LDL) for 24 hours caused a 2- to 3-fold increase of P-selectin
      protein, with little change in P-selectin surface expression. A 15-minute
      histamine treatment of cells exposed to MM-LDL caused a 50% to 100% increase in P
      selectin surface expression compared with cells not treated with the lipoprotein.
      This increase resulted in a 2-fold increase in binding of leukocytes to the
      endothelium. Immunostaining of permeabilized HAECs after MM-LDL treatment also
      revealed a highly reproducible increase in intracellular P-selectin associated
      with rod-shaped structures, typical of Weibel-Palade bodies. Oxidized
      phospholipids were shown to be mainly responsible for the action of MM-LDL. This
      increased P-selectin expression was associated with MM-LDL-induced cAMP
      elevation. Like histamine, highly oxidized low-density lipoprotein, especially
      the oxidized fatty acids, caused immediate redistribution of P-selectin to the
      cell surface followed by reinternalization. Immunohistochemical staining showed
      that endothelial cells on human fatty streak lesions expressed increased levels
      of P-selectin compared with nonlesion areas. These studies suggest that P
      selectin may play an important role in early recruitment of mononuclear cells to
      the subendothelium in human atherosclerosis and that oxidized lipoproteins may
      contribute to the increased expression of this molecule by increasing
      intracellular stores and causing redistribution to the cell surface.

PMID- 9168784
TI  - Lipoprotein lipase increases lipoprotein binding to the artery wall and increases
      endothelial layer permeability by formation of lipolysis products.
AB  - Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were
      investigated in a new model, the perfused hamster aorta. To do this, we developed
      a method to study LDL flux in real time in individually perfused arteries; each
      artery served as its own control. Using quantitative fluorescence microscopy, the
      rates of LDL accumulation and efflux were separately determined. Perfusion of
      arteries with buffer plus lipoprotein lipase (LpL) increased LDL accumulation 5
      fold (0.1 +/- 0.03 mV/min [control] versus 0.5 +/- 0.05 mV/min [LpL]) by
      increasing LDL retention in the artery wall. This effect was blocked by heparin
      and monoclonal antibodies directed against the amino-terminal region of
      apolipoprotein B (apo B). This suggests that specific regions of apo B are
      involved in LDL accumulation within arteries. Also, the effect of hydrolysis of
      triglyceride-rich lipoproteins on endothelial barrier function was studied. We
      compared endothelial layer permeability using a water-soluble reference molecule,
      fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma,
      dextran accumulation within the artery wall increased > 4-fold (0.024 +/- 0.01
      mV/min [control] versus 0.098 +/- 0.05 mV/min [LpL]). Under the same conditions,
      LpL increased LDL accumulation approximately 3-fold (0.016 +/- 0.003 mV/min
      [control] versus 0.047 +/- 0.013 mV/min [LpL]). Rapid efflux of LDL from the
      artery wall indicated that increased endothelial layer permeability was the
      primary mechanism during periods of increased lipolysis. Our data demonstrate two
      LpL-mediated effects that may increase the amount of LDL in the artery wall.
      These findings may pertain to the observed relationship between increased
      postprandial lipemia and atherosclerosis.

PMID- 9168785
TI  - Monocyte chemotactic protein-1 increases collateral and peripheral conductance
      after femoral artery occlusion.
AB  - Monocytes are activated during collateral artery growth in vivo, and monocyte
      chemotactic protein-1 (MCP-1) has been shown to be upregulated by shear stress in
      vitro. In order to investigate whether MCP-1 enhances collateral growth after
      femoral artery occlusion, 12 rabbits were randomly assigned to receive either MCP
      1, PBS, or no local infusion via osmotic minipump. Seven days after occlusion,
      isolated hindlimbs were perfused with autologous blood at different pressures,
      measuring flows at maximal vasodilation via flow probe and radioactive
      microspheres, as well as peripheral pressures. This allowed the calculation of
      collateral (thigh) and peripheral (lower limb) conductances from pressure-flow
      tracings (slope of the curve). Collateral growth on postmortem angiograms was
      restricted to the thigh and was markedly enhanced with MCP-1 treatment. Both
      collateral and peripheral conductances were significantly elevated in animals
      with MCP-1 treatment compared with the control group, reaching values of
      nonoccluded hindlimbs after only 1 week of occlusion (collateral conductance,
      70.6 +/- 19.23 versus 25.1 +/- 2.59 mL/min per 100 mm Hg; P < .01; peripheral
      conductance, 119.3 +/- 22.37 versus 45.4 +/- 6.80 mL/min per 100 mm Hg; P < .05).
      These results suggest that activation of monocytes plays an important role in
      collateral growth as well as in capillary sprouting.

PMID- 9168786
TI  - Vascular thrombin receptor regulation in hypertensive rats.
AB  - Thrombin has been implicated as an important mediator of vascular lesion
      formation in atherosclerosis and restenosis. To investigate a potential role for
      thrombin signaling in the vascular response to hypertension, we have studied
      thrombin receptor (TR) expression and regulation in hypertensive rats. Aortic TR
      mRNA was upregulated by angiotensin II (Ang II)-induced hypertension (10.7 +/-
      2.5 times control, P < .02), which correlated with a 4-fold increase in thrombin
      induced constriction in isolated endothelium-denuded aortic rings. The AT1
      receptor antagonist losartan normalized blood pressure and TR mRNA. Conversely,
      lowering blood pressure to the same degree with hydralazine did not abolish the
      upregulation of TR mRNA expression. When low-renin low-Ang II hypertension was
      induced in Dahl salt-sensitive rats, there was no detectable increase in the
      expression of aortic thrombin receptor mRNA. Finally, treatment with a chimeric
      heparin-binding form of the recombinant human Cu/Zn superoxide dismutase caused
      complete inhibition of TR mRNA upregulation, suggesting that an increased rate of
      superoxide anion production is an important signaling mechanism. Thus, increased
      TR expression via a redox-sensitive mechanism in the aortic smooth muscle of rats
      treated with Ang II represents a novel in vivo mechanism through which the
      hypertensive effects of Ang II are mediated.

PMID- 9168787
TI  - Nitric oxide promotes proliferation and plasminogen activator production by
      coronary venular endothelium through endogenous bFGF.
AB  - We reported previously that NO is responsible for the angiogenesis produced by
      endothelium-dependent vasodilating peptides. To investigate the mechanisms by
      which NO controls angiogenesis, NO was assessed for the ability to affect cell
      proliferation and upregulation of urokinase-type plasminogen activator (uPA)
      induced by basic fibroblast growth factor (bFGF) when added exogenously to or
      when produced endogenously by coronary venular endothelial cells (CVECs). The
      treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA
      upregulation and cell proliferation, which were prevented by anti-bFGF
      antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating
      peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating
      endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression
      as measured by Western blot analysis of CVEC extracts and by differential reverse
      transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of
      bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine. We
      conclude that NO promotes cell proliferation and uPA upregulation in CVECs by
      inducing endogenous bFGF and that this pathway mediates the angiogenetic response
      to the vasoactive neuropeptide SP. This signaling paradigm may provide an
      important link between shear rate, NO, bFGF, and coronary angiogenesis.

PMID- 9168788
TI  - Activity and expression of Na(+)-H+ exchanger isoforms 1 and 3 in kidney proximal
      tubules of hypertensive rats.
AB  - Increased activity of the cellular Na(+)-H+ exchangers (NHEs), especially isoform
      1 (NHE-1), is a recognized intermediate phenotype of hypertension. NHE activity
      has been demonstrated to be increased in proximal tubules of the spontaneously
      hypertensive rat (SHR). However, with the recent cloning of other members of this
      family of transporters, it is unclear which isoforms may contribute to this
      increased activity. We have used specific antibodies raised against glutathione-S
      transferase fusion proteins of rat NHE-1 and NHE-3 to determine the relative
      contributions of these isoforms to the NHE activity in freshly isolated and
      cultured proximal tubule cells from SHR and Wistar-Kyoto (WKY) normotensive
      control rats. In freshly isolated proximal tubule cells, NHE activity was
      elevated almost 3-fold in SHR cells (P < .001), and in both rat strains, the
      contribution from NHE-1 and NHE-3 was approximately equal. Western blots of
      membranes from these cells showed equal amounts of NHE-1 protein in SHR and WKY
      cells. However, NHE-3 protein expression was increased 50% in SHR cells (P <
      .001), and this may account for the elevated activity of this isoform in SHR. The
      effect of culturing these cells in vitro was then examined. Although total NHE
      activity in both cell types was decreased during culture, this was mainly due to
      loss of expression of NHE-3 protein. NHE-1 activity was persistently elevated in
      the SHR cells in culture. These findings suggest that elevated NHE activity in
      SHR proximal tubules could be mediated by two mechanisms: (1) increased NHE-1
      activity without any increased NHE-1 protein content that persists despite
      culture and may resemble those changes described for extrarenal tissues and (2)
      increased NHE-3 activity due to increased expression of NHE-3 protein.
      Disappearance of NHE-3 during culture implies that our culture conditions did not
      replicate the in vivo environment and may have removed the factors contributing
      to the increased NHE-3 expression in SHR cells.

PMID- 9168789
TI  - Non-voltage-gated Ca2+ influx through mechanosensitive ion channels in aortic
      baroreceptor neurons.
AB  - The mechanisms underlying mechanotransduction in baroreceptor neurons (BRNs) are
      undefined. In this study, we specifically identified aortic baroreceptor neurons
      in primary neuronal cell cultures from nodose ganglia of rats. Aortic
      baroreceptor neurons were identified by labeling their soma with the fluorescent
      dye 1,1'-dioleyl-3,3,3',3'-tetramethylin-docarbocyanine (DiI) applied to the
      aortic arch. Using Ca2+ imaging with fura 2, we examined these BRNs for evidence
      of Ca2+ influx and determined its mechanosensitivity and voltage dependence.
      Mechanical stimuli were produced by ejecting buffer from a micropipette onto the
      cell surface with a pneumatic picopump, producing a shift in the center of mass
      of the cell that was related to intensity of stimulation. Ninety-three percent of
      DiI-labeled neurons responded to mechanical stimulation with an increase in
      [Ca2+]i. The magnitude of the increases in [Ca2+]i was directly related to the
      intensity of the stimulus and required the presence of external Ca2+. The
      trivalent cations Gd3+ or La3+ in equimolar concentrations (20 mumol/L)
      eliminated the K(+)-induced rises in [Ca2+]i, demonstrating that both trivalent
      cations are equally effective at blocking voltage-gated Ca2+ channels in these
      baroreceptor neurons. In contrast, the mechanically induced increases in [Ca2+]i
      were blocked by Gd3+ (20 mumol/L) only and not by La3+ (20 mumol/L). Stretch
      activated channels (SACs) have been shown in other preparations to be blocked by
      Gd3+ specifically. Our data demonstrate that (1) BRNs, specifically identified as
      projecting to the aortic arch, have ion channels that are sensitive to mechanical
      stimuli; (2) mechanically induced Ca2+ influx in these cells is mediated by a
      Gd(3+)-sensitive ion channel and not by voltage-gated Ca2+ channels; (3) the
      magnitude of the Ca2+ influx is dependent on the intensity of the stimulus and
      the degree and duration of deformation; and (4) repeated stimuli of the same
      intensity result in comparable increases in [Ca2+]i. We conclude that mechanical
      stimulation increases Ca2+ influx into aortic BRNs independent of voltage-gated
      Ca2+ channels. The results suggest that Gd(3+)-sensitive SACs are the
      mechanoelectrical transducers in baroreceptors.

PMID- 9168790
TI  - Short-term exercise training enhances reflex cholinergic nitric oxide-dependent
      coronary vasodilation in conscious dogs.
AB  - The effects of exercise training on the coronary vasodilation following
      activation of the Bezold-Jarisch reflex were examined in conscious dogs. Mongrel
      dogs were chronically instrumented using sterile techniques for measurements of
      systemic hemodynamics and left circumflex coronary blood flow (CBF). With the
      heart rate controlled (150 bpm), veratrine (0.5 to 20 micrograms/kg) caused dose
      dependent increases in CBF; eg, 5 micrograms/kg of veratrine increased CBF by 61
      +/- 6% from 31 +/- 1.3 mL/min (P < .05). After exercise training, the dose
      response curve of CBF in response to veratrine was shifted to the left; eg, 5
      micrograms/kg of veratrine increased CBF by 101 +/- 12% (P < .05 compared with
      control) from 34 +/- 2.3 mL/min. The enhanced coronary vasodilation was blunted
      by nitro-L-arginine (NLA, 35 mg/kg). In anesthetized dogs after exercise
      training, electrical stimulation of the left vagus nerve caused greater increases
      in CBF, and NLA inhibited increases in CBF. Acetylcholine, norepinephrine,
      angiotensin II, and bradykinin caused greater increases in NO2- production in
      coronary microvessels from exercise-trained dogs compared with those from normal
      dogs. Our results indicate that the coronary vasodilation following activation of
      the Bezold-Jarisch reflex is enhanced in conscious dogs after exercise training.
      Since electrical stimulation of the vagus nerve caused greater coronary
      vasodilation and since the agonists resulted in greater increases in NO
      production in coronary microvessels from exercise-trained dogs, the mechanism
      responsible for the enhanced coronary vasodilation following activation of the
      Bezold-Jarisch reflex is most likely due to the increased release of NO from the
      endothelial cells.

PMID- 9168791
TI  - Epoxyeicosatrienoic acids activate K+ channels in coronary smooth muscle through
      a guanine nucleotide binding protein.
AB  - Epoxyeicosatrienoic acids (EETs) are endothelium-derived arachidonic acid
      metabolites of cytochrome P450. They dilate coronary arteries, open K+ channels,
      and hyperpolarize vascular smooth muscles. However, the mechanisms of these
      smooth muscle actions remain unknown. This study examined the effects of EETs on
      the large-conductance Ca(2+)-activated K+ channel (KCa) in smooth muscle cells of
      small bovine coronary arteries. In cell-attached patch-clamp experiments, 11,12
      EET produced a 0.5- to 10-fold increase in the activity of the KCa channels when
      added in concentrations of 1, 10, and 100 nmol/L. In the inside-out excised
      membrane patch mode, 11,12-EET was without effect on the activity of the KCa
      channel unless GTP (0.5 mmol/L) or GTP and ATP (1 mmol/L) were added to the bath
      solution. In the presence of GTP and ATP, the increase in the KCa channel
      activity with 11,12-EET in inside-out patches was comparable to that in cell
      attached patches. This effect of 11,12-EET in inside-out patches was blocked by
      the addition of GDP-beta-S (100 mumol/L). In outside-out patches, 11,12-EET also
      increased the KCa channel activity when GTP and ATP were added to the pipette
      solution. The addition of a specific anti-Gs alpha antibody (100 nmol/L) in the
      pipette solution completely blocked the activation of the KCa channels induced by
      11,12-EET. An anti-G beta gamma or anti-Gi alpha antibody was without effect. We
      conclude that 11,12-EET activates the KCa channels by a Gs alpha-mediated
      mechanism. This mechanism contributes to the effects of EETs as endothelium
      derived hyperpolarizing factors to hyperpolarize and relax arterial smooth
      muscle.

PMID- 9168792
TI  - Endothelin-1 alters the contractile phenotype of cultured embryonic smooth muscle
      cells.
AB  - Smooth muscle tissues may be classified into phasic (fast) or tonic (slow)
      contractile phenotypes. This study was initiated to examine the specification of
      these phenotypes during development and the role of growth factors in this
      process. We used myosin light chain 17 (MLC17) and myosin heavy chain transcript
      splice variants as markers of the tonic (aortic) and phasic (intestinal) smooth
      muscle phenotypes in chick embryos. By reverse transcription-polymerase chain
      reaction, we determined embryonic days 6 to 16 to be a critical period for the
      establishment of these phenotypes. During this period, endothelin-1 is present at
      40-fold-higher levels in aortic compared with intestinal tissues. To test the
      hypothesis that endothelin-1 may be involved in establishing the aortic (tonic)
      phenotype, we developed a system in which embryonic smooth muscle cells exhibit
      phasic and tonic contractile properties in vitro. Single-cell force measurements
      showed that cultured embryonic gizzard (phasic) cells developed force more
      rapidly (8 +/- 2 seconds) and achieved greater force (3.0 +/- 0.7 microN) than
      did cultured embryonic aortic (tonic) cells (20 +/- 0.7 seconds, 0.76 +/- 0.01
      microN; P < .05) in response to depolarization. Chronic exposure of the phasic
      (gizzard) cells to endothelin-1 prolonged the time to peak force (24 +/- 3
      seconds) and reduced the peak force (1.0 +/- 0.1 microN), so that the contraction
      resembled the tonic type. This effect, mediated by the endothelin-A receptor, was
      associated with a shift in MLC17 splicing to the tonic pattern. These results
      demonstrate that endothelin-1 is highly enriched in developing aortic compared
      with intestinal tissues and can convert phasic smooth muscle cells to the tonic
      type in vitro, suggesting a role for this growth factor during development in
      determining the contractile phenotype of smooth muscle cells.

PMID- 9168793
TI  - Hypercholesterolemia impairs a detoxification mechanism against peroxynitrite and
      renders the vascular tissue more susceptible to oxidative injury.
AB  - Previous studies have shown that glutathione (GSH) plays a central role in the
      protection against peroxynitrite (ONOO-) toxicity. The present study evaluated
      the changes of the GSH cytoprotective system against ONOO- in
      hypercholesterolemia and determined the effects of carvedilol, a beta-blocker
      with free radical-scavenging activity, on these hypercholesterol-induced changes.
      New Zealand White rabbits were fed either a normal diet, a high-cholesterol diet,
      or a high-cholesterol diet supplemented with either carvedilol or propranolol.
      Eight weeks later, the rabbits were killed, and the thoracic aortas were
      isolated. Total GSH content of aortic tissue, vasorelaxation response of aortic
      rings to exogenous ONOO-, No regeneration from ONOO- by aortic homogenate, and
      ONOO(-)-induced aortic tissue injury were examined. Hypercholesterolemia
      decreased tissue GSH content (0.52 +/- 0.08 versus 0.86 +/- 0.04 mumol/g in
      control, P < .01), attenuated the vasorelaxation response to ONOO- (40 +/- 4.1%
      versus 76 +/- 3.2%, P < .01), reduced NO regeneration from ONOO- (387 +/- 40
      versus 662 +/- 51 pmol, P < .01), and potentiated ONOO(-)-induced vascular tissue
      injury (37 +/- 4.4% versus 14 +/- 2.6% of increase in lactate dehydrogenase
      release after 3-morpholinosydnonimine exposure, P < .01). Treatment of the
      hypercholesterolemic rabbits with carvedilol, but not propranolol, significantly
      preserved tissue GSH content (0.79 +/- 0.05 mumol/g, P < .01 versus nontreated
      hypercholesterolemic rabbits), restored the vasorelaxation to ONOO- (61 +/- 2%, P
      < .01), increased NO regeneration from ONOO- (583 +/- 39 pmol, P < .01), and
      attenuated ONOO(-)-induced tissue injury (19 +/- 1.8%, P < .01). These results
      suggest that hypercholesterolemia impairs the GSH-mediated detoxification
      mechanism against ONOO- and renders the vascular tissue more susceptible to
      oxidative injury. Carvedilol, a novel vasodilating beta-blocker with antioxidant
      activity, significantly preserved this self-defense system and protected tissue
      from oxidant injury.

PMID- 9168794
TI  - The primordial germ cells of mammals: some current perspectives.

PMID- 9168795
TI  - Induction of smooth muscle cell phenotype in cultured human prostatic stromal
      cells.
AB  - Stromal cells are key regulators of growth and differentiation in the adult human
      prostate. Alterations in the stroma are believed to initiate the development of
      benign prostatic hyperplasia, and stromal-epithelial interactions may have a role
      in malignant progression. The prostatic stroma is composed of two major cell
      types, smooth muscle cells and fibroblasts. Cell cultures from the prostatic
      stroma have been established by several investigators, but the phenotype of these
      cells has not been extensively characterized and it is not clear whether they are
      fibroblastic or smooth muscle-like. In this study, the response of stromal cells
      cultured from normal prostatic tissues to transforming growth factor-beta (TGF
      beta) was investigated. We confirmed a previous report that TGF beta inhibited
      the growth of prostatic stromal cells in serum-containing medium, and showed that
      inhibition also occurred in serum-free medium. Growth inhibition by TGF beta was
      irreversible after 24 to 72 h of exposure. In the absence of TGF beta, cells were
      fibroblastic and expressed vimentin and fibronectin but little alpha-smooth
      muscle actin. After 3 days of exposure to 1 ng/ml of TGF beta, the majority of
      cells expressed alpha-smooth muscle actin and desmin, as demonstrated by
      immunocytochemistry and immunoblot analysis. This effect was specific and alpha
      smooth muscle actin was not induced by two other growth-inhibitory factors,
      retinoic acid or 1,25-dihydroxyvitamin D3. These results suggest that TGF beta is
      an important regulator of growth and differentiation of prostatic stromal cells
      and that a smooth muscle cell phenotype is promoted in the presence of TGF beta.

PMID- 9168796
TI  - Ultraviolet rays induced expression of lectins on the surface of a squamous
      carcinoma keratinocyte cell line.
AB  - Human keratinocytic cells from squamous carcinoma (SCL-1) present, under resting
      conditions, relatively low amounts of endogenous lectins (sugar-binding
      proteins). Upon uv irradiation, they express on their cell surface large amounts
      of endogenous lectin molecules able to bind neoglycoproteins bearing either alpha
      L-rhamnosyl or alpha-D-glucosyl residues. A similar binding specificity was found
      with normal human keratinocytes under the same culture conditions. At sunlike
      doses, uv.A (365 nm) was more efficient than uv.B (312 nm) in the expression of
      such receptors on the surface of SCL-1 cells. The increased presentation of
      lectins by SCL-1 cells was transient and reached a maximum 4 h after irradiation.
      Such a specific modulation of receptor expression upon uv irradiation might be
      biologically significant, considering the numerous intercellular recognition
      phenomena in skin biology. alpha-L-Rhamnose-specific receptor on SCL-1 could not
      be distinguished from alpha-D-glucose-specific receptor on the basis of
      neoglycoproteins binding, uptake, and related inhibitions. Lectin expression was
      mainly detected on the cell surface, and its overexpression due to uv rays
      required a de novo protein synthesis process.

PMID- 9168797
TI  - Biochemical differences between staurosporine-induced apoptosis and premature
      mitosis.
AB  - Apoptosis is morphologically related to premature mitosis, an aberrant form of
      mitosis. Staurosporine, a potent protein kinase inhibitor, induces not only
      apoptotic cell death in a wide variety of mammalian cells but also premature
      initiation of mitosis in hamster cells that are arrested in S phase by DNA
      synthesis inhibitors. Here we report on the biochemical differences between the
      two phenomena commonly caused by staurosporine. Rat 3Y1 fibroblasts that had been
      arrested in S phase with hydroxyurea underwent apoptosis by treatment with
      staurosporine, whereas S-phase-arrested CHO cells initiated mitosis prematurely
      when similarly treated with a low concentration of staurosporine. Chromosome
      condensation occurred in both apoptosis (3Y1) and premature mitosis (CHO).
      However, neither formation of mitotic spindles nor mitosis-specific
      phosphorylation of MPM-2 antigens was observed in apoptosis of 3Y1 cells, unlike
      premature mitosis of CHO cells. The p34cdc2 kinase activated in normal and
      prematurely mitotic cells remained inactive in the apoptotic cells, probably
      because the active cyclin B/p34cdc2 complex was almost absent in the S-phase
      arrested 3Y1 cells. The absence of intracellular activation of p34cdc2 in
      apoptosis was confirmed by immunohistochemical analyses using a specific antibody
      raised against Ser55-phosphorylated vimentin which is specifically phosphorylated
      by p34cdc2 during M phase. Furthermore, phosphorylation of histones H1 and H3,
      which is associated with mitotic chromosome condensation, did not occur in the
      apoptotic cells. These results indicate that the two phenomena, staurosporine
      induced apoptosis and premature mitosis, are different in their requirement for
      p34cdc2 kinase activation and histone phosphorylation.

PMID- 9168798
TI  - Detection of mutant p53 in clam leukemia cells.
AB  - Leukemia in the soft-shell clam, Mya arenaria, is characterized by tumor cells
      which are detected initially in the hemolymph. This disease is much more common
      in clams inhabiting polluted waters, suggesting an environmental component to its
      pathogenesis. In this study, leukemia cells were identified using a murine
      monoclonal antibody, 1E10, which recognizes a leukemia-specific protein expressed
      by tumor cells. Mutant p53 protein was detected using a murine monoclonal
      antibody (PAb 240) which reacts with mutant p53. Using immunofluorescence, the
      reactivity of clam cells to the 1E10 antibody was evaluated along with mutant p53
      protein reactivity. Reverse transcriptase-polymerase chain reactions followed by
      sequence analyses were utilized to examine clams with hemocytes reacting with the
      p53 antibody for possible p53 gene mutations. Mutant p53 protein was expressed by
      tumor cells from five animals with advanced disease (in which greater than 90% of
      cells reacted with 1E10). A C-->G transversion was detected at the end of exon 6
      from two of the five animals that reacted with both the mutant p53 antibody and
      1E10. This substitution changes the amino acid of this codon from proline to
      alanine. Overall, our results suggest that environmentally induced alterations in
      p53 can contribute to the pathogenesis of leukemia in soft-shell clams inhabiting
      polluted water and/or sediment.

PMID- 9168799
TI  - Role of heme-hemopexin in human T-lymphocyte proliferation.
AB  - Heme-hemopexin supports and stimulates proliferation of human acute T
      lymphoblastic (MOLT-3) cells, suggesting the participation of heme in cell growth
      and division. MOLT-3 cells express approximately 58,000 hemopexin receptors per
      cell (apparent Kd 20 nM), of which about 20% are on the cell surface. Binding is
      dose- and temperature-dependent, and growth in serum-free IMDM medium is
      stimulated by 100-1000 nM heme-hemopexin, consistent with the high affinity of
      the receptor for hemopexin, and maximal growth is seen in response to 500 nM
      complex. Growth was similar in defined minimal medium supplemented with either
      low concentrations of heme-hemopexin or iron-transferrin, and either of these
      complexes were about 80% as effective as a serum supplement. Heme-hemopexin, but
      not apo-hemopexin, reversed the growth inhibition caused by desferrioxamine
      showing that heme-iron derived from heme catabolism is used for cell growth.
      Cobalt-protoporphyrin (CoPP)-hemopexin, which binds to the receptor but is not
      transported intracellularly [Smith et al., (1993) J. Biol. Chem. 268, 7365], also
      stimulated cell proliferation in serum-free IMDM but did not "rescue" the cells
      from desferrioxamine. Furthermore, CoPP-hemopexin effectively competed for the
      hemopexin receptor with heme-hemopexin and diminished its growth stimulatory
      effects. In addition, protein kinase C (PKC) is translocated to the plasma
      membrane within 5 min after heme-hemopexin is added to the medium, reaches
      maximum activity within 5-10 min, and declines to unstimulated levels by 30 min.
      Heme-hemopexin and CoPP-hemopexin both augmented MOLT-3 cell growth stimulated by
      serum. Thus, heme-hemopexin not only functions as an iron source for T-cells but
      occupancy of the hemopexin receptor itself triggers signaling pathway(s) involved
      in the regulation of cell growth. The stimulation of growth of human T
      lymphocytes by heme-hemopexin is likely to be a physiologically relevant
      mechanism at sites of injury, infection, and inflammation.

PMID- 9168800
TI  - Fas/Fas ligand interaction contributes to UV-induced apoptosis in human
      keratinocytes.
AB  - Keratinocytes in human skin undergo apoptosis during various inflammatory
      processes and after ultraviolet (UV) irradiation. To determine if keratinocyte
      apoptosis may be mediated by the Fas/APO-1 receptor (CD95), a signal transduction
      pathway known to initiate programmed cell death of lymphocytes, we investigated
      Fas expression, modulation, and function in keratinocytes. Keratinocytes
      constitutively expressed the 2.5- and 1.9-kb Fas transcripts, as well as the 43
      kDa Fas protein. Treatment of interferon-gamma-stimulated keratinocytes with Fas
      agonistic antibody significantly promoted their cell death, indicating that Fas
      in keratinocytes is functional. UV irradiation induced Fas mRNA expression within
      16 to 24 h and Fas protein within 24 h and through 48 h after irradiation.
      Furthermore, keratinocytes constitutively expressed Fas ligand (FasL) mRNA and
      protein. UV irradiation induced FasL mRNA as early as 4 h after irradiation and
      elevated FasL mRNA levels were maintained for at least 24 h postirradiation.
      Moreover, a FasL neutralizing antibody significantly reduced UV-induced apoptosis
      of IFN-gamma-treated keratinocytes. Our data strongly suggest that the Fas system
      contributes to keratinocyte apoptosis in UV-irradiated human skin.

PMID- 9168801
TI  - Bone morphogenetic protein-6 is expressed in nonparenchymal liver cells and
      upregulated by transforming growth factor-beta 1.
AB  - Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta superfamily,
      which controls growth and differentiation during embryogenesis and acts as an
      osteoinductive factor in the adult organism. In order to gain further insights
      into the role of BMP-6, the present study analyzed the expression pattern of BMP
      6 in adult rat tissues with special emphasis to the liver, since TGF-beta 1,
      another member of the TGF-beta superfamily, has been shown to play a fundamental
      role in liver physiology. Rat BMP-6-coding cDNAs were generated by homology
      cloning using RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BMP
      6, respectively. By Northern blotting BMP-6-specific transcripts 3.7 kb in size
      were detected in major amounts in lung and in minor quantities in spleen, kidney,
      heart, brain, and liver. Among the different hepatic cell populations tested BMP
      6 expression was confined to nonparenchymal liver cells, namely rat hepatic
      stellate cells (HSC) and Kupffer cells (KC). During primary culture BMP-6
      expression was increased in HSC but declined in KC. Interestingly, TGF-beta 1
      stimulated BMP-6 expression of HSC especially at an early time point of culture,
      while interferon-gamma downregulated BMP-6 expression. The detection of BMP-6
      transcripts in the liver, the cell-type-restricted expression pattern, and its
      regulation propose that, in addition to its osteoinductive properties, BMP-6
      might play a role in liver growth and differentiation, in particular after tissue
      damage.

PMID- 9168802
TI  - Defective expression of beta 1-integrins in cells with constitutively active
      alpha L beta 2-integrins.
AB  - We have investigated a potential relationship between expression of beta 1
      integrins and adhesiveness of the beta 2-integrin LFA-1 (alpha L beta 2,
      CD11a/CD18). By an approach of random mutagenesis and selection we established
      clones from the human acute lymphatic leukemia cell line HPB-ALL with (i)
      constitutively active LFA-1 and (ii) with no apparent integrin-beta 1 cell
      surface expression. Thirty-seven of 42 clones selected for activated LFA-1 were
      found to have lost apparent integrin-beta 1 expression. Conversely, 7 of 21
      clones selected for lack of beta 1 expression were found to have activated LFA-1.
      Since this pointed toward a possible coupling between beta 1 expression and LFA-1
      activity, we further analyzed at which level beta 1 expression was blocked. We
      focused on one clone, HAP4, with activated LFA-1 and no detectable beta 1 cell
      surface expression and found, surprisingly, that it expressed wild-type levels of
      beta 1 mRNA and, in Western blots of whole cell lysates, apparently normal levels
      of beta 1 protein. However, in addition to beta 1 of the expected molecular
      weight, HAP4 expressed a unique 48-kDa band recognized by the polyclonal anti
      beta 1 antiserum. Immunoprecipitation experiments revealed that the epitope
      recognized by the anti-beta 1 antibody 4B4 was hidden or lost. The alpha 4-chain
      was found in its precursor form but it did not associate with any beta-chain, and
      it was not processed to its mature form. Instead alpha 4-chains were eventually
      degraded. Taken together this showed that beta 1-chains were produced but not
      properly processed in HAP4. From this we propose that HAP4 is deficient in a gene
      product required both for proper beta 1 folding and for repression of LFA-1
      adhesiveness.

PMID- 9168803
TI  - All-trans-retinoic acid blocks cell cycle progression of human ovarian
      adenocarcinoma cells at late G1.
AB  - We prepared single cell clones from two ovarian carcinoma cell lines, CA-OV3 and
      SK-OV3, and analyzed the effect of all-trans-RA treatment on cell division, DNA
      synthesis, and cell cycle stage distribution of these single cell clones. Our
      results show that despite the well-known heterogeneous nature of these cell
      lines, all single cell clones of SK-OV3 cells are resistant to the growth
      inhibitory effects of all-trans-RA. In contrast, all single cell clones of CA-OV3
      cells were growth inhibited by all-trans-RA. However, the extent of growth
      inhibition did vary somewhat from clone to clone. Additional studies employing
      flow cytometry showed that all-trans-RA blocked CA-OV3 cell cycle progression in
      the G1 stage. Finally, all-trans-RA was able to inhibit G1 progression in growth
      arrested CA-OV3 cells following stimulation with fetal bovine serum, insulin, IGF
      1, or estrogen. Since each of these growth factors is known to act via distinct
      signal transduction pathways, our results suggest that all-trans-RA blocks G1
      progression by targeting a downstream process or event which occurs at a point
      after the insulin/IGF-1, estrogen, and serum signal transduction pathways
      converge.

PMID- 9168804
TI  - In vitro characterization of chondrogenic cells isolated from chick embryonic
      muscle using peanut agglutinin affinity chromatography.
AB  - Specific binding to the lectin, peanut agglutinin (PNA), has been reported in
      embryonic precartilage tissues, including the condensing limb bud blastema and
      the caudal half of the developing somite. The present study aimed to test the
      hypothesis that PNA-binding may be a surface characteristic of chondroprogenitor
      cells residing within noncartilage tissues, such as muscle, which have the
      potential of being induced to form cartilage, e.g., in the presence of bone
      matrix-derived factors. Day-14 chick embryonic pectoral muscle, which contained
      histochemically detectable PNA-binding cells, was dissociated into single cells
      (TM cells) and fractionated by PNA affinity chromatography into PNA-binding
      (PNA+) and nonbinding (PNA-) cells by PNA-Sepharose 6 MB affinity chromatography.
      The differentiation potential of the PNA-affinity fractionated cells in vitro was
      analyzed as a function of culture plating cell density. Immunohistochemistry of a
      number of cell-type-specific differentiation markers, including sarcomeric actin,
      collagen type II, and aggrecan core protein, demonstrated that PNA+ cells, when
      cultured as a micromass at high density (20 x 10(6) cells/ml), exhibited a
      chondrocyte-like phenotype, whereas the PNA-cells remained myogenic; however,
      both PNA+ and PNA- monolayer cultures (4 x 10(4) cells/ml) behaved as myoblastic
      cells. The expression of collagen type II mRNA was also confirmed by coupled
      reverse transcription/polymerase chain reaction analysis. These observations
      suggest that PNA binding, i.e., the presence of specific galactose-containing
      cell surface moieties, is likely to be one of the characteristics of chondrogenic
      cells residing in mesenchymally derived embryonic tissues.

PMID- 9168805
TI  - Repression of muscle-specific gene activation by the murine Twist protein.
AB  - Inhibition of myogenic differentiation can be achieved by various mechanisms. The
      murine bHLH protein Twist has been shown to inhibit muscle differentiation in
      mammalian cells. Here we demonstrate that this inhibition is cell autonomous and
      does not alter cell proliferation. By overexpression of E12, we can distinguish
      the inhibitory mechanisms of Twist and the dominant negative HLH factor Id. A
      difference is seen both for the native muscle-specific enhancers of myogenin and
      myosin light chain 1/3 and for an enhancer consisting only of four E-boxes.
      Mutagenesis experiments revealed that both the basic region and an evolutionarily
      conserved carboxy-terminal domain are required for the Twist-specific type of
      inhibition. Loss of either of these regions renders Twist less efficient and more
      similar to Id. Gel mobility shift assays demonstrate that Twist can bind to the
      muscle creatine kinase E-box and inhibit DNA binding of heterodimers of E12 with
      myogenic bHLH transcription factors like MyoD. However, a fourfold excess of
      Twist compared to MyoD is required for both effects. Our results suggest that
      Twist inhibits muscle-specific gene activation by formation of actively
      inhibitory complexes rather than by sequestering E-proteins.

PMID- 9168806
TI  - Modulation of alpha 6/beta 1 integrin expression during differentiation of F9
      murine embryonal carcinoma cells to parietal endoderm.
AB  - In vitro differentiation of the murine embryonal carcinoma (EC) cell line F9
      parallels that of the early blastocyst, where visceral (VE) and parietal endoderm
      (PE) diverge from a common precursor, the primitive endoderm. This
      differentiation pathway is induced by retinoic acid (RA) and dibutyryl cyclicAMP
      (dcAMP) and is accompanied by progressive and dramatic changes in cell morphology
      and functions. Within 7 days of treatment the cells organize their cytoskeleton
      and synthesize large amounts of extracellular matrix proteins, becoming fully
      differentiated migratory cells; all these changes are likely to involve integrins
      expression and organization. We have investigated the changes in beta 1 integrin
      expression, its maturation, and organization on the cell surface in association
      with alpha 6, during the transition from undifferentiated F9 stem cells to
      migrating PE cells. By Western blotting and immunoprecipitation we showed a
      gradual decrease in the amount of the beta 1 subunit on the cell surface and a
      parallel progressive accumulation of immature protein, indicating that the
      control of beta 1 expression during F9 cells differentiation occurs first at post
      translational level and then at the level of transcription. Moreover, the
      induction of differentiation produces a marked decrease of alpha 6B and its
      association to a high molecular weight protein, while alpha 6A level increases.
      By immunofluorescence we found that upon differentiation there is a relocation of
      the beta 1 and alpha 6B integrin subunits from cell-cell contacts to focal
      contacts where they colocalize with vinculin. On the contrary alpha 6A, weakly
      present in F9 stem cells, is present in the focal contacts of PE cells and along
      the stress fibers. We suggest different roles for the two alpha 6 isoforms.

PMID- 9168807
TI  - Intact cell evidence for the early synthesis, and subsequent late apopain
      mediated suppression, of poly(ADP-ribose) during apoptosis.
AB  - Poly(ADP-ribose) polymerase (PARP), which is catalytically activated by DNA
      strand breaks, has been implicated in apoptosis, or programmed cell death. A
      protease (CPP32) responsible for the cleavage of PARP and necessary for apoptosis
      was recently purified and characterized. The coordinated sequence of events
      related to PARP activation and cleavage in apoptosis has now been examined in
      individual cells. Apoptosis was studied in a human osteosarcoma cell line that
      undergoes a slow (8 to 10 days), spontaneous, and reproducible death program in
      culture. Changes in the abundance of intact PARP, poly(ADP-ribose) (PAR), and a
      proteolytic cleavage product of PARP that contains the DNA-binding domain were
      examined during apoptosis in the context of individual, whole cells by
      immunofluorescence with specific antibodies. The synthesis of PAR from NAD
      increased early, within 2 days of cell plating for apoptosis, prior to the
      appearance of internucleosomal DNA cleavage and before the cells become
      irreversibly committed to apoptosis, since replating yields viable, nonapoptotic
      cells. Strong expression of full-length PARP was also detected, by
      immunofluorescence as well as by Western analysis, during this same time period.
      However, after approximately 4 days in culture, the abundance of both full-length
      PARP and PAR decreased markedly. After 6 days, a proteolytic cleavage product
      containing the DNA-binding domain of PARP was detected immunocytochemically and
      confirmed by Western analysis, both in the nuclei and in the cytoplasm of cells.
      A recombinant peptide spanning the DNA-binding domain of PARP was expressed,
      purified, and biotinylated, and was then used as a probe for DNA strand breaks.
      Fluorescence microscopy with this probe revealed extensive DNA fragmentation
      during the later stages of apoptosis. This is the first report, using individual,
      intact cells, demonstrating that poly(ADP-ribosyl)ation of nuclear proteins
      occurs prior to the commitment to apoptosis, that inactivation and cleavage of
      PARP begin shortly thereafter, and that very little PAR per se is present during
      the later stages of apoptosis, despite the presence of a very large number of DNA
      strand breaks. These results suggest a negative regulatory role for PARP during
      apoptosis, which in turn may reflect the requirement for adequate NAD and ATP
      during the later stages of programmed cell death.

PMID- 9168808
TI  - Activation of gelatinase A (72-kDa type IV collagenase) induced by monensin in
      normal human fibroblasts.
AB  - In monolayer culture, fibroblasts secrete all matrix metalloproteinases,
      including gelatinase A (72-kDa type IV collagenase), as inactive zymogens.
      Whereas limited proteolysis by plasmin or other matrix metalloproteinases (MMPs)
      can accomplish the extracellular activation of other proenzymes in this family,
      gelatinase A proenzyme is uniquely refractory to cleavage by such proteinases.
      Previously it has been shown that fibroblasts cultured in the presumably more
      physiologic culture milieu of a type I collagen lattice can be induced to secrete
      active gelatinase A. In monolayer culture, however, the plant lectin concanavalin
      A will induce gelatinase A activation. Here we show that in monolayer culture
      activation of gelatinase A by normal fibroblasts is also induced by the sodium
      ionophore monensin. The monensin response is dose-dependent, time-dependent,
      requires protein synthesis, and is specific to gelatinase A among the secreted
      matrix metalloproteinases. The activator appears to be associated with cell
      membranes and may be membrane-type matrix metalloproteinase 1(MT-MMP1). Both mRNA
      and immunodetectable protein of MT-MMP1 are increased with monensin treatment
      while message for the protein inhibitor of gelatinase A, TIMP-2, is unchanged.
      The monensin-induced signal transduction pathway leading to gelatinase activation
      in monolayer culture appears to be different from the integrin-mediated pathway
      operative in the collagen lattice system. The tyrosine kinase inhibitor genistein
      blocks monensin activation of gelatinase A in monolayer culture. In contrast,
      genistein has no effect on proenzyme activation in the collagen lattice.
      Likewise, the cyclooxygenase inhibitor indomethacin abrogates the monensin effect
      in monolayer culture and can be reversed by addition of exogenous prostaglandin
      E2 (PGE2). Neither indomethacin nor PGE2 affects activation of gelatinase A in
      the collagen lattice.

PMID- 9168809
TI  - M-cadherin-mediated cell adhesion and complex formation with the catenins in
      myogenic mouse cells.
AB  - M-cadherin is a member of the multigene family of calcium-dependent intercellular
      adhesion molecules, the cadherins, which are involved in morphogenetic processes.
      Amino acid comparisons between M-cadherin and E-, N-, and P-cadherin suggested
      that M-cadherin diverged phylogenetically very early from these classical
      cadherins. It has been shown that M-cadherin is expressed in prenatal and adult
      skeletal muscle. In the cerebellum, M-cadherin is present in an adherens-type
      junction which differs in its molecular composition from the E-cadherin-mediated
      adherens-type junctions. These and other findings raised the question of whether
      M-cadherin and the classical cadherins share basic biochemical properties,
      notably the calcium-dependent resistance to proteolysis, mediation of calcium
      dependent intercellular adhesion, and the capability to form M-cadherin complexes
      with the catenins. Here we show that M-cadherin is resistant to trypsin digestion
      in the presence of calcium ions but at lower trypsin concentrations than E
      cadherin. When ectopically expressed in LMTK- cells, M-cadherin mediated calcium
      dependent cell aggregation. Finally, M-cadherin was capable of forming two
      distinct cytoplasmic complexes in myogenic cells, either with alpha-catenin/beta
      catenin or with alpha-catenin/plakoglobin, as E-and N-cadherin, for example, have
      previously been shown to form. The relative amount of these complexes changed
      during differentiation from C2C12 myoblasts to myotubes, although the molecular
      composition of each complex was unaffected during differentiation. These results
      demonstrate that M-cadherin shares important features with the classical
      cadherins despite its phylogenetic divergence.

PMID- 9168810
TI  - In vivo interference of paromomycin with mitochondrial activity of Leishmania.
AB  - Paromomycin is an aminocyclitol aminoglycoside antibiotic used for the treatment
      of leishmaniasis. In view of the central role of mitochondria in cellular
      energetics and metabolism, its effect on in vivo mitochondrial activities of
      Leishmania donovani promastigotes-the parasite flagellate form-was investigated.
      The approach used flow cytometry, amperometric measure of O2 consumption, and, as
      a global estimate of mitochondrial dehydrogenases, thiazolyl blue reduction (MTT
      test); some in vitro controls were also made. When added to promastigote cultures
      for 24-72 h at 150-200 microM (= LC50), paromomycin doubled the generation time,
      inhibited respiration, and lowered its associated electric potential difference
      across mitochondrial membranes, as measured by rhodamine 123 fluorescence. The
      chemical analogue neomycin was ineffective. Furthermore, the in vivo
      mitochondrial dehydrogenase activities were lower, seemingly because of the
      shortage of respiratory substrates. Indeed, succinate addition to paromomycin
      treated cultures partly restored mitochondrial membrane potential. However, no
      immediate effect of paromomycin on respiration was observed, neither inhibition
      of redox chain nor increase of membrane permeability (uncoupling). It is proposed
      that paromomycin acts at a metabolic level upstream of the respiratory chain
      itself. This would have the observed delayed consequence because the cell energy
      supply would progressively decline since it depends upon the proton gradient
      viz., membrane potential-generated by respiration. In conclusion, paromomycin is
      an antibiotic affecting the cell's energetic metabolism; the respiratory
      dysfunction it induces may be a crucial aspect of its action against Leishmania
      and possibly other cells.

PMID- 9168811
TI  - Role of proliferation for intercellular induction of apoptosis.
AB  - We have recently described induction of apoptosis of transformed target cells by
      TGF-beta-treated nontransformed effector cells as a potential novel control step
      in oncogenesis. Here we study the role of proliferation of both cell types for
      the efficiency of induction of apoptosis. Inhibition of proliferation of
      transformed target cells by gamma irradiation or colchicine treatment did not
      affect their sensitivity to induction of apoptosis by TGF-beta-treated
      nontransformed effector cells. This finding indicates that sensitivity to
      intercellular induction of apoptosis is not related to cell cycle control. In
      contrast, the ability of nontransformed effector cells to induce apoptosis was
      dependent on their proliferation. Nontransformed cells blocked by gamma
      irradiation, colchicine treatment, or thymidine treatment were no longer able to
      induce apoptosis of transformed target cells. This inability seems to be
      partially due to substances that are released from proliferation-inhibited
      nontransformed effector cells and that interfere with induction of apoptosis.

PMID- 9168812
TI  - Effect of glucocorticoid hormones on viral gene expression, growth, and
      dysplastic differentiation in HPV16-immortalized ectocervical cells.
AB  - Steroid hormones are proposed to act as cofactors with human papillomaviruses
      (HPVs) in the etiology of cervical cancer. We and others reported that
      progesterone and glucocorticoid hormones induce the expression of HPV16 via three
      glucocorticoid response elements (GREs) in the viral regulatory region. Consensus
      GREs (GREcs) are useful in other systems for examining the effect of hormones
      after enhancing the response with mutated GREc constructs. Therefore, this study
      used human ectocervical cells (HEC) and HPV type 16 containing three GREcs to
      establish immortalized cells (HEC-16GREc). Northern blot assays showed that the
      level of viral E6-E7 oncogene RNA was increased by hormones substantially more in
      HEC-16GREc than in wild-type HPV16-immortalized human ectocervical cells (HEC
      16). The saturation density and the hormone response of the growth rate were
      significantly higher for HEC-16GREc and the doubling was faster in the presence
      of hormone than for HEC-16. Although both were nontumorigenic, only HEC-16GREc
      showed anchorage-independent growth, which was dependent on hormone. Also, HEC
      16GREc were more abnormal in their epithelium differentiation pattern in
      organotypic (raft) cultures. Furthermore, hormone-treated HEC-16GREc rafts showed
      more dysplastic features than hormone-treated HEC-16 rafts. These results suggest
      new features of the role of hormones: that enhanced expression of viral oncogenes
      in response to hormones apparently confers a greater risk for cervical cells
      containing HPV16. Further, HEC-16GREc could be ideal for studying hormone
      dependent and -independent malignant transformation.

PMID- 9168813
TI  - Hypoxia-induced apoptosis in human cells with normal p53 status and function,
      without any alteration in the nuclear protein level.
AB  - We have studied hypoxia-induced inactivation of cells from three established
      human cell lines with different p53 status. Hypoxia was found to induce apoptosis
      in cells expressing wild-type p53 (MCF-7 cells), but not in cells where p53 is
      either mutated (T-47D cells), or abrogated by expression of the HPV18 E6
      oncoprotein (NHIK 3025 cells). Apoptosis was demonstrated by DNA fragmentation,
      using agarose gel electrophoresis of DNA and DNA nick end labeling (TUNEL). We
      demonstrate that extremely hypoxic conditions (< 4 ppm O2) do not cause any
      change of expression in the p53 protein level in these three cell lines. In
      addition, the localization of p53 in MCF-7 cells was found exclusively in the
      nucleus in only some of the cells both under aerobic and hypoxic conditions.
      Furthermore, no correlation was found between the p53-expression level and
      whether or not a cell underwent apoptosis. Flow cytometric TUNEL analysis of MCF
      7 cells revealed that initiation of apoptosis occurred in all phases of the cell
      cycle, although predominantly for cells in S phase. Apoptosis was observed only
      during a limited time window (i.e., approximately 10 to approximately 24 h) after
      the onset of extreme hypoxia. While 66% of the MCF-7 cells lost their ability to
      form visible colonies following 15 h exposure to extreme hypoxia, only
      approximately 28% were induced to apoptosis, suggesting that approximately 38%
      were inactivated by other death processes. Commitment to apoptotic cell death was
      observed in MCF-7 cells even for oxygen concentrations as high as 5000 ppm. Our
      present results indicate that the p53 status in these three tumor cell lines does
      not have any major influence on cell's survival following exposure to extremely
      hypoxic conditions, whereas following moderate hypoxia, cells expressing
      functional p53 enhanced their susceptibility to cell death. Taken together,
      although these results suggest that functional p53 might play a role in the
      induction of apoptosis during hypoxia, other factors seem to be equally
      important.

PMID- 9168814
TI  - The enzymatic activity of Cu/Zn superoxide dismutase does not fluctuate in mouse
      spermatogenic cells despite mRNA changes.
AB  - In the mammalian testis, multiple mRNAs encoding the copper zinc superoxide
      dismutase (SOD-1) are expressed in postmeiotic male germ cells. Here we relate
      SOD-1 mRNA levels to SOD-1 protein and enzyme activity levels in mouse
      spermatogenic cells. Although the sizes and relative amounts of the multiple SOD
      1 mRNAs vary as male germ cells enter meiosis and proceed into the postmeiotic
      stages of spermatogenesis, the amount of SOD-1 protein and enzyme activity does
      not fluctuate significantly, suggesting a precise control of SOD-1 activity in
      male germ cells.

PMID- 9168815
TI  - Uncoupling of cell cycle arrest from the expression of monocytic differentiation
      markers in HL60 cell variants.
AB  - Differentiation generally leads to cell cycle arrest. Human leukemia HL60 cells
      respond to the presence of 1,25-dihydroxyvitamin D3 (1,25D3) by expressing a
      number of markers of the monocyte/macrophage phenotype and become arrested
      predominantly in the G1 phase of the cell cycle. We have recently reported a
      series (A) of 1,25D3-resistant variants of HL60 cells which proliferate in the
      presence of 1,25D3 and do not express differentiation markers (Exp. Cell Res.
      224, 312, 1996). We now describe another series (B) of such variants, which
      differ from A series cells grown in similar concentrations of 1,25D3 in that they
      express the CD14 antigen and nonspecific esterase, characteristic of the
      monocyte, while continuing to proliferate and they develop hypotetraploid DNA
      (4C) content at higher concentrations of ambient 1,25D3 than the A series cells.
      Cells in the B series with 4C DNA content (100B and 200B) also differed from the
      A series 4C cells by the absence of DNA binding by the full-length Sp1
      transcription factor. However, B series cells resembled the A series cells in
      exhibiting faster growth rates than the parental HL60 cells and showed high
      levels of vitamin D receptor and retinoid receptor X proteins. These results show
      that the initial steps in the 1,25D3 signaling pathway are intact in B series
      resistant cells and lead to the appearance of early markers of monocytic
      differentiation. However, the progression to subsequent events which comprise
      terminal differentiation and cell cycle arrest is halted during the adaptation to
      the presence of 1,25D3 in these cells. Thus, the availability of these variant
      cells should provide a system for studying the link between differentiation and
      cell cycle arrest.

PMID- 9168816
TI  - Expression of the vav oncogene in somatic cell hybrids.
AB  - The vav oncogene is expressed primarily in tissues of hematopoietic origin. While
      much effort has been focused on determining the role of vav in various signal
      transduction pathways, little is known about the mechanism by which vav is
      regulated in a tissue-selective manner. This issue was examined by developing
      somatic cell hybrids between human U937 cells, which express vav, and mouse
      Balb/c 3T3 cells, which do not. If vav is primarily regulated by the presence of
      positive acting transcription factors, then vav expression should be maintained
      in hybrid cells. In contrast, if the regulation of vav is primarily negative in
      nature, then vav expression should be extinguished in most of the somatic cell
      hybrids. Of the hybrid cells that were obtained, 64% were positive by reverse
      transcriptase-polymerase chain reaction for the expression of the vav oncogene.
      Differences in the pattern of restriction enzyme cleavage sites between the mouse
      and human PCR products were used to determine that 6 of 11 of the positive clones
      expressed the normally dormant mouse gene. The other positive clones were found
      to express the human vav gene. In all cases, the hybrid cells preferentially
      retained the chromosomes and the cellular morphological appearance of the mouse
      Balb/c 3T3 fusion partner, which does not express the vav oncogene. Since vav is
      able to be transiently expressed by hybrid cells with a predominately mouse
      phenotype, these results support the hypothesis that vav is regulated primarily
      by the presence of transactivating factors which stimulate transcription, rather
      than by a gene silencing mechanism.

PMID- 9168817
TI  - Mitofilin is a transmembrane protein of the inner mitochondrial membrane
      expressed as two isoforms.
AB  - Mitofilin, also known as heart muscle protein, is a recently identified
      mitochondrial protein. We have isolated two human cDNAs that encode different
      isoforms of mitofilin. Using reverse PCR, we provide evidence that both isoforms
      are derived by alternative splicing and encode two proteins of 88 and 90 kDa that
      are detected in immunoblot analyses with mitofilin-specific antibodies.
      Immunofluorescence microscopy, fractionating of human osteosarcoma cells, and
      protease protection experiments with isolated mitochondria and mitoplasts
      indicate that mitofilin is an integral membrane protein of the inner
      mitochondrial membrane. 35S-labeled mitofilin is transported into isolated yeast
      mitochondria in a reaction that depends on the membrane potential across the
      inner mitochondrial membrane (delta psi). During mitochondrial in vitro import,
      mitofilin is proteolytically processed to the mature protein that is also
      detected in cellular fractions, indicating that the amino-terminal leader
      sequence is removed. Sequence analysis and our results suggest that mitofilin is
      anchored in the inner mitochondrial membrane with an amino-terminal transmembrane
      domain, while the majority of the protein is extruding into the intermembrane
      space.

PMID- 9168818
TI  - Aggregation of Thy-1 glycoprotein induces thymocyte apoptosis through activation
      of CPP32-like proteases.
AB  - Mouse thymocytes are known to undergo apoptosis by ligating some unique anti-Thy
      1 monoclonal antibodies (mAbs), G7 and KT16. However, the precise mechanisms of
      Thy-1-mediated apoptosis are as yet unclear. We investigated Thy-1-mediated
      apoptosis using our previously generated anti-Thy-1 mAb, MCS-34, which was
      similar to G7 because both antibodies recognized both Thy-1.1 and Thy-1.2 and
      bound Thy-1A epitope. Unlike G7, MCS-34 alone could not induce apoptosis in
      thymocytes; however, it could induce apoptosis when it was cross-linked with
      second antibodies. Thus, MCS-34 could not aggregate by itself, but G7 could. In
      the course of investigating the apoptosis-related molecules that were involved in
      the thymocyte apoptosis induced by cross-linking of MCS-34 or by G7 ligation, we
      found that CPP 32-like proteases were activated during the apoptosis.
      Furthermore, the expression of bcl-2 and bcl-XL proteins was decreased in these
      apoptosis processes. Whereas the ligation of MCS-34 alone could not generate
      apoptosis signals that led to the activation of CPP32-like proteases and the
      decrease in bcl-2 and bcl-XL expression, the aggregation of Thy-1 glycoprotein
      might be crucial to signal thymocyte apoptosis. These results indicate that MCS
      34 is a useful anti-Thy-1 mAb for analyzing the Thy-1-mediated signals since MCS
      34 can control the level of apoptosis by using second antibodies.

PMID- 9168819
TI  - Fluorescence in situ hybridization with comets.
AB  - We have adapted the fluorescence in situ hybridization technique to single-cell
      gel electrophoresis (comet assayed) preparations. Since cells were embedded in
      agarose, probed regions could be visualized in three dimensions. This system
      makes it possible to determine the spatial distribution of chromosome-specific
      DNA sequences at the level of the individual nucleus (nonelectrophoresed) as well
      as in chromatin fibers of comets (electrostretched chromosomal DNA). This
      methodology is likely to bring new insights into the field of interphase nuclear
      ultrastructure. Here, we present the preliminary data obtained with human blood
      lymphocytes in Gzero after they have been electrophoresed for different times.
      Chromosome-specific areas (all centromeres, all telomeres, chromosome 7-specific
      centromere, and long arm of chromosome 3-specific telomere, as well as three
      segments of the O6-methylguanine-DNA methyltransferase gene) were investigated.
      Our results are in agreement with the concept that telomeres are in close
      association with the nuclear membrane and suggest that centromeres are relatively
      less condensed structures located in the center of the interphase nucleus.

PMID- 9168820
TI  - Reactivation of DNA replication in nuclei from terminally differentiated cells:
      nuclear membrane permeabilization is required for initiation in Xenopus egg
      extract.
AB  - We have used Xenopus egg extract to investigate the requirements for reactivation
      of DNA replication in nuclei isolated from terminally differentiated chicken
      erythrocytes. Previous work has shown that reactivation of erythrocyte nuclei in
      egg extract is accompanied by chromatin decondensation, nuclear envelope
      reformation, and the accumulation of egg lamin, LIII. However, in those studies,
      erythrocyte nuclei were prepared by methods that were not designed to maintain
      the selective permeability of the nuclear membrane, and as such, it is not clear
      if loss of nuclear membrane integrity played a role in the reactivation process.
      Therefore, the purpose of this study was to determine if changes in nuclear
      membrane permeability are required for reactivation of erythrocyte nuclei in egg
      extract. Nuclei with intact nuclear membranes were prepared from erythrocytes
      with streptolysin O and permeable nuclei by treatment of intact nuclei with the
      detergent Nonidet-P40. Like permeable nuclei, most intact nuclei decondensed,
      imported nuclear protein, and accumulated lamin LIII from the extract. However,
      unlike permeable nuclei, which replicated extensively in the extract, few intact
      nuclei initiated replication under the same conditions. These data demonstrate
      that permeabilization of the nuclear membrane is required for reactivation of DNA
      replication in terminally differentiated erythrocyte nuclei by egg extract and
      suggest that loss of nuclear membrane integrity may be a general requirement for
      replication of quiescent cell nuclei by this system.

PMID- 9168821
TI  - Plasminogen activator inhibitor-1 represses integrin- and vitronectin-mediated
      cell migration independently of its function as an inhibitor of plasminogen
      activation.
AB  - Cell migration involves the integrins, their extracellular matrix ligands, and
      pericellular proteolytic enzyme systems. We have studied the role of plasminogen
      activator inhibitor-1 (PAI-1) in cell migration, using human amnion WISH cells
      and human epidermoid carcinoma HEp-2 cells in an assay measuring migration from
      microcarrier beads and a modified Boyden-chamber assay. Active, but not latent or
      reactive center-cleaved, PAI-1 inhibited migration. A PAI-1 mutant without
      ability to inhibit plasminogen activation was as active as wild-type PAI-1 as a
      migration inhibitor, showing that inhibition of plasminogen activation was not
      involved. PAI-1 specifically interfered with intergrin- and vitronectin-mediated
      migration: Migration onto vitronectin-coated but not onto fibronectin-coated
      surfaces was inhibited by PAI-1, a cyclic RGD peptide inhibited migration, and
      both cell lines expressed vitronectin-binding alpha v-integrins. In addition,
      active PAI-1, but not latent or reactive center-cleaved PAI-1, inhibited
      vitronectin binding to integrins in an in vitro binding assay, without affecting
      binding of fibronectin. Monoclonal antibodies against the urokinase receptor,
      another vitronectin binding protein, did not affect cell migration in the beads
      assay, while some inhibitory effect was observed in the Boyden-chamber assay. We
      conclude that PAI-1, independently of its role as a proteinase inhibitor,
      inhibits cell migration by competing for vitronectin binding to integrins, while
      the interference of PAI-1 with binding of vitronectin to the urokinase receptor
      may play a secondary role. These data define a novel function for the serpin PAI
      1, enabling it to regulate cell migration over vitronectin-rich extracellular
      matrix in the body.

PMID- 9168822
TI  - Exposure of phosphatidylethanolamine on the surface of apoptotic cells.
AB  - In the early stages of apoptosis, phosphatidylserine (PS) is translocated from
      the inner side of the plasma membrane to the outer layer, which allows phagocytes
      to recognize and engulf the apoptotic cells. In this study we have analyzed the
      cell surface exposure of phosphatidylethanolamine (PE) in apoptotic CTLL-2 cells,
      a cytotoxic T cell line, using a tetracyclic polypeptide of 19 amino acids (Ro09
      0198) which specifically recognizes the structure of PE and forms a tight
      equimolar complex with the phospholipid. Fluorescence microscopic analysis showed
      that the peptide, conjugated with fluorescence-labeled streptavidin (FL-SA-Ro),
      bound effectively to the cell surface of cells undergoing apoptosis in response
      to withdrawal of interleukin-2 from the culture media, but not to nonapoptotic
      cells. The binding of FL-SA-Ro to apoptotic cells was not uniform and the intense
      staining was observed on surface blebs of apoptotic cells. The FL-SA-Ro binding
      was inhibited specifically by liposomes containing PE, suggesting that PE is
      mainly exposed on the surface blebs of apoptotic cells. The specific binding of
      FL-SA-Ro to the apoptotic cells was also confirmed using a flourescence-activated
      cell sorter and the time-dependent cell surface exposure of PE correlated well
      with the exposure of PS, as detected by the binding of annexin V. This study
      provides the first direct evidence that PE as well as PS is exposed on the cell
      surface during the early stages of apoptosis, resulting in the total loss of
      asymmetric distribution of aminophospholipids in the plasma membrane bilayer.

PMID- 9168823
TI  - Redox state changes in density-dependent regulation of proliferation.
AB  - The ability of certain transcription factors to bind to DNA has been demonstrated
      to be influenced by the redox environment. Therefore, fluctuations in the redox
      state of the cell may regulate the transcription of genes which control
      proliferation. To assess whether changes in the redox state may be related to
      proliferation, levels of oxidized (GSSG) and reduced (GSH) glutathione, the
      primary modulators of the redox state, were measured in cultures of varying
      densities of normal human fibroblasts which exhibit contact inhibition of
      proliferation, as well as fibrosarcoma cells, which lack this mechanism of growth
      control. Redox potentials calculated from normal, proliferating fibroblasts were
      found to be -34 mV more reducing than confluent, contact-inhibited cells.
      However, fibrosarcoma cells did not demonstrate this modulation in redox state.
      Further, to delineate whether these redox changes were the consequence or the
      cause of contact inhibition, cultures of subconfluent proliferating fibroblasts
      were treated with modulators of glutathione synthesis. Buthionine sulfoximine, an
      inhibitor of GSH synthesis, induced a less reducing redox state and decreased
      proliferation. In contrast, GSH synthesis precursors caused a more reduced redox
      state and increased proliferation. Collectively, these results suggest an
      interrelationship between redox state and growth control.

PMID- 9168824
TI  - CSF-1-induced and constitutive Il6 gene expression in mouse macrophages: evidence
      for PKC-dependent and -independent pathways.
AB  - It has been recently shown that CSF-1 enhanced the constitutive expression of the
      Il6 gene in resident mouse peritoneal macrophages (PM phi) but little is known
      about the pathways involved. In this report, we show that both constitutive and
      CSF-1-induced IL-6 release were enhanced and prolonged in the presence of the PKC
      inhibitors, staurosporine (SP) and its derivative, GF-109203X. Enhancement of
      constitutive IL-6 release required higher concentrations of inhibitors, while
      enhanced CSF-1-induced release was diminished when inhibitor concentrations
      exceeded defined limits. SP was also shown to activate constitutive IL-6 release
      by blood monocytes and elicited PM phi but had no effect on their responsiveness
      to CSF-1. Activation of PKC by exposure of resident PM phi to phorbol myristate
      acetate (PMA) also resulted in enhanced IL-6 release and PMA was shown to
      synergize with CSF-1. These data indicate that CSF-1 does not induce Il6 gene
      expression by amplifying the constitutive pathway in all mononuclear phagocyte
      subpopulations. It exerts its effects independently of PKC, which may activate
      Il6 gene expression in its own right by an alternative pathway. While CSF-1 and
      PKC are involved in separate pathways, the synergistic IL-6 response seen when
      PMA and CSF-1 interact suggests convergence of the two pathways. It is also
      apparent that multiple PKs, excluding PKC, may be involved in repressing
      constitutive and CSF-1-induced Il6 gene expression.

PMID- 9168825
TI  - Huntingtin immunoreactivity in the rat neostriatum: differential accumulation in
      projection and interneurons.
AB  - Huntington's disease is caused by a mutation of the gene encoding the protein
      huntingtin. Features of the human disease, characterized by selective loss of
      neurons from the neostriatum, can be replicated in rodents by administration of
      excitotoxins. In both affected individuals and the rodent model, there is massive
      loss of striatal projection neurons with selective sparing of interneurons.
      Furthermore, in the human disease the earliest evidence of striatal injury is
      found in striosomal regions of the striatum. The mRNA encoding huntingtin is
      known to be expressed by neurons throughout the brain, a distribution which does
      not account for the selective patterns of neuronal death which are observed.
      Using fluorescence immunocytochemistry and confocal microscopy with an antibody
      to huntingtin, we have observed that in rats a subset of striatal projection
      neurons contains dense accumulations of huntingtin immunoreactivity (HT-ir),
      while most neurons in the striatum contain much smaller amounts. The intensely
      stained neurons are concentrated within the striatal striosomes, as defined by
      calbindin-D28K staining. In the matrix regions, relatively few neurons contain
      dense accumulations of HT-ir, and these cells always lack perikaryal staining for
      calbindin-D28K. Striatal interneurons, identified by the presence of
      immunoreactivity for choline acetyltransferase, parvalbumin, calretinin, or
      neuronal nitric oxide synthase, exhibit little or no HT-ir. The paucity of HT-ir
      in striatal interneurons, as well as the prominence of staining in a subset of
      striosomal neurons, mirrors the selective vulnerability of these different types
      of cells in early stages of human Huntington's disease and in rodent excitotoxic
      models of the disorder. Our observations suggest that mechanisms which modulate
      the accumulation of huntingtin may play a central role in the neuronal
      degeneration of Huntington's disease.

PMID- 9168826
TI  - Expression of nitric oxide synthase in hypothalamic nuclei following axonal
      injury or colchicine treatment.
AB  - Nitric oxide (NO) has recently gained much attention due to its apparently double
      edged role in neuronal injury. This study was aimed at elucidating neuronal
      nitric oxide synthase (nNOS) expression in the brain after two types of injury,
      namely axonal transection and colchicine treatment. The neurosecretory
      hypothalamo-pituitary pathway served as a model for the reaction of central
      neurons to these two types of injury. Axonal transection, i.e., pituitary stalk
      section, resulted in a qualitative increase in NOS content in the supraoptic and
      paraventricular nuclei. In these nuclei, there was also an increase in the number
      of NOS-expressing neurons after the operation. Surprisingly, in the
      periventricular nucleus, a strong decrease in the number of NOS-positive
      magnocellular neurons was observed in the anterior part of the nucleus.
      Intracerebroventricular injection of colchicine resulted in an increase in the
      cell count in the paraventricular nucleus, while the other nuclei remained
      unchanged. Our results suggest that axonal injury results in an increase in nNOS
      expression in the major neurosecretory nuclei, while the periventricular nucleus
      shows the opposite reaction. Colchicine treatment has an effect similar to that
      of axotomy in the major neurosecretory nuclei, suggesting that an increase in NOS
      expression may be induced by interrupted axonal transport. In the periventricular
      nucleus, the decrease in the number of NOS-containing neurons suggests
      differences among hypothalamic NOS-containing neuron groups in response to
      neuronal injury.

PMID- 9168827
TI  - Enhanced levels of biochemical markers for cobalamin deficiency in totally
      gastrectomized rats: uncoupling of the enhancement from the severity of spongy
      vacuolation in spinal cord.
AB  - The totally gastrectomized (TGX) rat is a new experimental model for studying the
      pathogenesis of cobalamin (Cbl)-deficient myelopathy, i.e., subacute combined
      degeneration, total gastrectomy (TG) serving as a surgical paradigm of human
      pernicious anemia. We determined the serum levels of some biochemical indicators
      of Cbl deficiency in TGX rats at 2 to 10 months after TG. Methylmalonic acid
      (MMA) rose within 2 months and progressively increased thereafter until the end
      of the investigation period. 2-Methylcitric acid (MCA) rose significantly by 6
      months and showed a further increment 4 months later. Homocysteine was only
      clearly elevated much later than the serum MMA, i.e., 10 months after the
      operation. The concentrations of MMA, MCA, and cystathionine were increased in
      kidney, liver, and spinal cord (SC) of TGX rats at 10 months. Chronic treatment
      of TGX rats with Cbl greatly decreased the serum levels of all the metabolic
      indicators of Cbl deficiency. Chronic peroral administration of the antibiotic
      lincomycin to TGX rats in an attempt to suppress the enteric flora markedly
      decreased serum MMA levels. Only Cbl, however, given either for the first 2
      months after TG or for the third and fourth postoperative months (i.e., after SC
      abnormalities had already appeared) significantly decreased the severity of
      spongy vacuolation in SC white matter, although not completely preventing or
      repairing the neuropathological damage. Therefore, neither the early impairment
      in TGX rats of the Cbl-dependent methylmalonyl-coenzyme A mutase reaction nor the
      more delayed impairment of the Cbl-dependent methionine synthase step, as
      reflected by changes in serum metabolite levels, seems to be causally related to
      the TG-induced spongy vacuolation in SC white matter.

PMID- 9168828
TI  - Nitric oxide synthase in reactive astrocytes adjacent to beta-amyloid plaques.
AB  - This study provides the first evidence that nitric oxide is released by
      astrocytes surrounding beta-amyloid plaques. Nitric oxide is involved in many
      neuropathological conditions and can have either a neuroprotective or a
      neurotoxic function depending on its concentration and the redox state of the
      tissue. It is produced by the enzyme nitric oxide synthase, which can be located
      by a simple histochemical technique for demonstrating NADPH diaphorase. Using
      this method we examined tissue from 10 brains where there were varying numbers of
      beta-amyloid plaques in the cerebral cortex. In the 6 brains with moderate or
      high densities of plaques, primitive and cored plaques were associated with
      between 1 and 10 reactive astrocytes that contained NADPH diaphorase or were
      immunoreactive for the inducible form of nitric oxide synthase. In the 4 brains
      which had only low densities of plaques, the plaques were not associated with
      diaphorase-containing astrocytes. The percentage of plaques associated with 1 or
      more NADPH diaphorase-containing astrocyte varied between 1 and 21% and was
      correlated with the density of plaques. Astrocytes were the only form of NADPH
      diaphorase-positive glial cell associated with the plaques. There was no evidence
      of any nitric oxide synthase occurring in microglia.

PMID- 9168829
TI  - BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal
      outgrowth.
AB  - To assess the therapeutic potential of brain-derived neurotrophic factor (BDNF)
      in clinics, we extensively investigated the effects of BDNF on adult motor
      neurons in a rat spinal root avulsion model. Intrathecal administration of BDNF
      immediately after the spinal root avulsion greatly protected against the motor
      neuron cell death. BDNF also showed a protective effect on the atrophy of soma
      and on the reduction of transmitter-related enzymes such as choline acetyl
      transferase and acetylcholine esterase. Very interestingly, BDNF induced axonal
      outgrowth of severely damaged motor neurons at the avulsion site. The BDNF
      administration following 2-week treatment with phosphate-buffered saline after
      avulsion prevented further augmentation of cell death and reversed cholinergic
      transmitter-related enzyme deficiency. BDNF was demonstrated to possess a wide
      variety of biological effects on survival, soma size, cholinergic enzymes, and
      axonal outgrowth of adult motor neurons. These results provide a rationale for
      BDNF treatment in motor neuron diseases such as spinal cord injury and
      amyotrophic lateral sclerosis.

PMID- 9168830
TI  - Quinolinate immunoreactivity in experimental rat brain tumors is present in
      macrophages but not in astrocytes.
AB  - Experimental tumors of the central nervous system were investigated with
      antibodies to quinolinate to assess the cellular distribution of this endogenous
      neurotoxin. In advanced F98 and RG-2 glioblastomas and E367 neuroblastomas in the
      striatum of rats, variable numbers of quinolinate immunoreactive cells were
      observed in and around the tumors, with the majority being present within tumors,
      rather than brain parenchyma. The stained cells were morphologically variable,
      including round, complex, rod-shaped, and sparsely dendritic cells. Neuroblastoma
      and glioma cells were unstained, as were neurons, astrocytes, oligodendrocytes,
      ependymal cells, endothelial cells, and cells of the choroid plexus and
      leptomeninges. Glial fibrillary acidic protein immunoreactivity was strongly
      elevated in astrocytes surrounding the tumors. Dual labeling immunohistochemistry
      with antibodies to quinolinate and glial fibrillary acidic protein demonstrated
      that astrocytes and the cells containing quinolinate immunoreactivity were
      morphologically disparate and preferentially distributed external and internal to
      the tumors, respectively, and no dual labeled cells were observed. Lectin
      histochemistry with Griffonia simplicifolia B4 isolectin and Lycopersicon
      esculentum lectin demonstrated numerous phagocytic macrophages and reactive
      microglia in and around the tumors whose distribution was similar to that of
      quinolinate immunoreactive cells, albeit much more numerous. Dual labeling
      studies with antibodies to quinolinate and the lectins demonstrated partial
      codistribution of these markers, with most double-labeled cells having the
      morphology of phagocytes. The present findings suggest the possibility that
      quinolinate may serve a functional role in a select population of inflammatory
      cell infiltrates during the immune response to brain neoplasms.

PMID- 9168831
TI  - Neurotrophins and basic fibroblast growth factor induce the differentiation of
      calbindin-containing neurons in the cerebral cortex.
AB  - Lineage studies have recently shown that the expression of calcium-binding
      proteins in neurons of the cerebral cortex is not genetically programmed and is
      likely to be induced by external factors. Current hypotheses suggest that basic
      fibroblast growth factor (bFGF) and a number of neurotrophins play important
      roles in the proliferation and differentiation of cortical progenitor cells to a
      particular lineage. Using a dissociated cell culture system, we found that bFGF
      and the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3
      (NT-3), and nerve growth factor differentially affect the expression of the
      calcium-binding protein calbindin in selective neuronal subpopulations in the
      developing cerebral cortex. Specifically, BDNF and NT-3 greatly promoted the
      morphological differentiation of a relatively small, early-generated population
      of GABAergic neurons and induced the expression of calbindin in these cells.
      Furthermore, treatment with BDNF, NT-3, and bFGF produced an two- to threefold
      increase in the number of newly generated calbindin-positive neurons. The effect
      of bFGF was more striking in earlier (E14) than later (E16) ages, whereas the
      action of neurotrophins was independent of the age from which the cultures were
      prepared. Switching experiments combined with BrdU incorporation have suggested
      that NT-3 acts on postmitotic neurons rather than on proliferating progenitors to
      induce calbindin expression and that its action is mediated via trk receptors.
      Application of retroviral vectors in culture resulted in the presence of neuronal
      clones that were predominantly heterogeneous with regard to calbindin expression,
      suggesting, in agreement with our earlier in vivo studies, that the expression of
      this calcium-binding protein is not lineage dependent. Our results characterize
      the roles of BDNF, NT-3, and bFGF in the expression of calbindin in developing
      neocortical neurons.

PMID- 9168832
TI  - 5-Azacytidine and BDNF enhance the maturation of neurons derived from EGF
      generated neural stem cells.
AB  - EGF-generated neural stem cells can form astrocytes, neurons, and
      oligodendrocytes upon differentiation; however, the proportion of cells that
      actually form neurons is very small. In the present study, we have studied the
      effect that 5-azacytidine (5AzaC), a demethylation agent, and brain-derived
      growth factor (BDNF) have on the differentiation and maturation of neurons
      originating from EGF-generated neural stem cells. Stem cells were maintained
      under a variety of culture conditions using combinations of 5AzaC and BDNF either
      alone or together. More neurons, as determined by the number of beta-tubulin III
      immunoreactive somata, were present in cultures maintained in BDNF medium (a
      nearly fourfold increase compared to control cultures). 5AzaC did not
      significantly affect neuronal number, regardless of the presence of BDNF. In
      addition to neuronal number, the effect of 5AzaC and BDNF on the distribution of
      the microtubule proteins MAP2 and Tau was analyzed. In most cultures, MAP2 and
      Tau were colocalized throughout the neuron. In contrast, neurons cotreated with
      5AzaC and BDNF contained neurons that began to exhibit cytoskeletal segregation
      of MAP2 into the somatodendritic compartments. Tau remained dispersed within the
      somata and the axon. This effect was not produced when 5AzaC or BDNF was used
      individually. These results demonstrate that 5AzaC and BDNF cooperate to produce
      more mature neurons from EGF-generated neural stem cells then either molecule can
      alone.

PMID- 9168833
TI  - Synaptic remodeling and free radical formation after brain contusion injury in
      the rat.
AB  - The purpose of this study was to explore whether bilateral frontal cortex
      contusion in rats would demonstrate changes relevant for understanding the
      pathology of frontal lobe injury in humans. Rats were allowed to survive for 3,
      7, or 18 days postinjury (dpi). In the contused rats, albumin was trapped in
      frontal cortices, as well as in other brain areas, showing that neurons were
      exposed to plasma components. In the sham-operated rats, which had only
      craniotomy but no penetration of dura, the level of trapped albumin was also
      increased compared to intact controls, suggesting a partial lesion-like
      condition. Choline acetyltransferase activity was severely decreased in the
      frontal cortices of contused rats, compared to the sham-operated controls. The
      decrease was most pronounced at 3 dpi and less pronounced 18 dpi, suggesting that
      after the initial damage, regeneration of the cholinergic terminals occurred. The
      concentration of the mature presynaptic membrane protein D3(SNAP-25) was also
      decreased in the frontal cortices of contused rats at 3 and 7 dpi, whereas it was
      normalized at 18 dpi. Previously, we have evaluated changes in the rate of
      synaptic remodeling in brain injury by calculating the ratio of the neural cell
      adhesion molecule (NCAM) to D3(SNAP-25). The NCAM/D3(SNAP-25) ratio at 3 dpi was
      elevated by more than 60% in the frontal cortices of contused rats, suggesting a
      high initial rate of synaptic remodeling. The ratios were smaller at 7 and 18
      dpi, suggesting that after the initial burst, the rate of remodeling leveled off.
      In contrast, astrocyte activation was less pronounced at 3 dpi than at 7 and 18
      dpi, as measured by the levels of glial fibrillary acidic protein and glutamine
      synthetase immunoactivities. The immunoreactivity of glutamine synthetase more
      than doubled in the contused brains but its enzymatic activity increased less
      than 50%, suggesting that many enzymatic centers had been inactivated by free
      radicals. Calculated as the difference between the relative immunoreactivity and
      the relative enzymatic activity the "lost glutamine synthetase activity"
      increased continuously in frontal cortex and striatum from 3 to 18 dpi,
      indicating the production of free radicals long after the initial contusion
      event. In conclusion, following frontal cortical contusions the early synaptic
      damage was partly compensated by synaptic remodeling. We suggest that the
      continuous production of free radicals may have contributed to the declining
      remodeling rate and impair functional recovery.

PMID- 9168834
TI  - Maturational regulation and regional induction of cyclooxygenase-2 in rat brain:
      implications for Alzheimer's disease.
AB  - We explored the constitutive expression, maturational regulation, and relation to
      kainic-acid-induced apoptosis of cyclooxygenase (COX)-2 mRNA in rat brain. In
      adult rats, COX-2 mRNA was expressed primarily in limbic structures. Constitutive
      COX-2 mRNA expression increased markedly between Postnatal Day 7 (P7) and P14,
      reaching adult levels by P21. Despite intense KA-induced seizures, no COX-2 mRNA
      induction was found before P14 in any brain region examined. During response to
      KA-induced seizures in adult brain, COX-2 mRNA induction paralleled temporally
      and overlapped anatomically the appearance of cellular morphological features of
      apoptosis in subsets of cells of the pyramidal neuron layer of the hippocampal
      formation, amygdaloid complex, and pyriform cortex. While COX-2 mRNA showed KA
      induced elevation in the granule cell layer of the dentate gyrus, no detectable
      morphological features of apoptosis were found in this region. Finally, monotypic
      culture of rat corticohippocampal neurons confirmed the neuronal expression of
      COX-2 in vitro and revealed that COX-2 is induced during response to glutamate
      treatment, leading to neuron death. These studies may provide novel insights into
      the role of COX-2 and mechanisms of action of nonsteroidal anti-inflammatory
      drugs in Alzheimer's disease.

PMID- 9168836
TI  - Cholinergic synapses in human cerebral cortex: an ultrastructural study in serial
      sections.
AB  - Cholinergic axons in the human cerebral cortex were analyzed by electron
      microscopy. Choline acetyltransferase (ChAT) immunoreactivity was used to
      identify cholinergic axons in samples of anterior temporal lobe removed at
      surgery. A systematic survey of labeled axon varicosities, visualized in complete
      serial sections, showed that 67% of all varicosities formed identifiable synaptic
      specializations. These synapses were usually symmetric and quite small, often
      present in only one to two serial sections. However, an occasional synapse was
      asymmetric and larger, seen in five to seven serial sections. The postsynaptic
      processes at cholinergic synapses were often identified as spiny dendrites or
      spines. The existence of cholinergic axons in the human cerebral cortex has been
      demonstrated in numerous studies. Our findings provide the first ultrastructural
      evidence that these axons make synaptic contact with cortical neurons in the
      human brain.

PMID- 9168835
TI  - Embryonic precursor cells that express Trk receptors: induction of different cell
      fates by NGF, BDNF, NT-3, and CNTF.
AB  - Epidermal growth factor (EGF)-treated neurosphere cultures from embryonal
      striatum contain multipotential cells capable of neuronal, astrocytic, and
      oligodendroglial differentiation. In this study, we tested whether these neural
      precursor cells differentiate in the presence of neurotrophic factors. We first
      assayed neurosphere cells for expression of neurotrophin receptors. TrkA, TrkB,
      TrkC, and gp75 were detected by immunofluorescence microscopy in 60-80% of cells.
      In addition, the ciliary neurotrophic factor receptor alpha was expressed in 50
      60% of cells. In the presence of the mitogen, EGF, treatment of stem cells with
      neurotrophic factors had no apparent effect. Removal of EGF from cells resulted
      in cessation of cell proliferation and pronounced astrocytic (glial fibrillary
      acidic protein+) differentiation. Neuronal (neurofilament+) and oligodendroglial
      (galactocerebroside+) cells appeared in cultures treated with neurotrophic
      factors. Nerve growth factor (NGF) resulted in bipolar neuronal cells, and brain
      derived neurotrophic factor led to multipolar neuronal cells. Treatment with
      neurotrophin-3 or ciliary neurotrophic factor resulted in bipolar neuronal cells
      and oligodendrocytes. Neuronal differentiation in the presence of NGF was
      enhanced by extracellular matrix, and the resulting neuronal cells expressed
      choline acetyltransferase and, to a lesser degree, tyrosine hydroxylase. These
      studies demonstrate that neurotrophic factors influence the fates of these
      multipotential precursor cells. Indeed, the true utility of multipotential
      precursor cells is the production of different types of cells in different
      situations. Local cues, such as neurotrophic factors and extracellular matrix,
      may regulate production of different types of neural cells during development or
      in response to other stimuli, such as injury.

PMID- 9168837
TI  - Maturation of fetal human neural xenografts in the adult rat brain.
AB  - Transplantation of human fetal neural cells has been used for several years as a
      treatment for Parkinson's disease. These therapeutic trials were based on a large
      number of rat allografts studies, and the species to species extrapolation
      appeared valid in many respects. One major difference between neurons of various
      species, however, is their rate of maturation; indeed, human neurons have been
      proven to grow much more slowly than rat neurons. This has been studied mostly,
      up to now, at the light microscope level. In an attempt to determine the fine
      structural correlates of this protracted development and to detail the schedule
      of morphogenesis and synaptogenesis, human fetal brain stem tissue (at 8 weeks of
      gestation) was transplanted into a previously lesioned brain area of
      immunosuppressed adult rats. Transplants, which were allowed to develop for 15
      days to 3 months, were analyzed using the electron microscope. At 15 days, small
      cells containing a large nucleus were surrounded by wide extracellular spaces. At
      1 month, grafted neurons displayed a thin rim of cytoplasm and few thin
      processes. At 2 months, extracellular spaces tended to diminish. Thin processes
      formed bundles and large processes extended from enlarged neurons. Major changes
      were observed at 3 months survival as the neuropile filled up with cells and
      processes and synaptogenesis began. Comparison with a similar ultrastructural
      study of thalamic rat allografts shows that human cells develop following a
      pattern similar to that in rat cells but that the duration of each maturation
      step is largely extended.

PMID- 9168838
TI  - Spinal cord compression injury in guinea pigs: structural changes of endothelium
      and its perivascular cell associations after blood-brain barrier breakdown and
      repair.
AB  - This study examines morphological changes of the blood-brain barrier (BBB) after
      spinal cord compression. The lowest thoracic segment (T13) of female guinea pigs
      was injured and the BBB was tested from 7 days to 5.5 months postinjury using
      intravenously injected horseradish peroxidase (HRP) as a tracer. Tracer leakage
      in the injured segment was verified with the light microscope and the fine
      structure of capillaries was examined. Diffuse tissue staining was observed at
      T13 up to 2 weeks following injury. A leaky BBB correlated with expected changes
      in the fine structure of endothelial cell junctions. These were predominantly
      nonoverlapping cell junctions which, in many instances, were separated by clefts
      between adjacent cells. At early survival times, numerous capillary profiles with
      juxtaposed astrocyte foot processes were noted in addition to altered cell
      associations. Complete sealing of the BBB against interstitial HRP leakage was
      not observed until 17 days postinjury. After the first week, some of the
      endothelial cells were contacted by macrophages, processes of perivascular
      microglia, and processes of swollen and degenerating astrocytes. Perivascular
      spaces varied in extent and contained amorphous deposits of extracellular
      materials in addition to supernumerary layers of basal lamina. The early changes
      were followed by profound tissue restructuring due to loss of both neurons and
      glia. At longer survival times the BBB to HRP repaired. Endothelial cells formed
      complex overlapping junctions with zonulae occludentes. Most of the capillaries
      in the injured segment were no longer in direct contact with astrocyte foot
      processes, although reactive astrocytes constituted the predominant cell type in
      the remaining gray matter. Substantial expansion of perivascular spaces was
      evident. The cytoplasm of endothelial cells had numerous pinocytotic vesicles.
      Perivascular spaces contained layers of assembled collagen arranged
      perpendicularly to each other in addition to amorphous matrix materials. The
      findings suggest that decoupling of astrocyte foot processes from endothelial
      cell surfaces does not prevent reformation of tight junctions. It remains to be
      examined what effects the larger perivascular spaces, extracellular matrix
      deposits, and changes of cell associations may have on transport systems and
      ionic buffering. The data are relevant for estimating an opportune time for
      application of barrier-impermeable drugs to the lesion area.

PMID- 9168839
TI  - Low-dose vigabatrin (gamma-vinyl GABA)-induced damage in the immature rat brain.
AB  - The antiepileptic drug, vigabatrin, inhibits GABA transaminase, thus elevating
      GABA levels in the brain. In adult animal experiments, high-dose (200 mg/kg/day)
      chronic vigabatrin administration is associated with potentially reversible
      myelin vacuolation, a phenomenon not documented in humans. We hypothesized that
      vigabatrin might adversely affect myelination in the developing brain. Rats were
      given vigabatrin in doses comparable to those used clinically (15-50 mg/kg/day),
      from age 12 to 16 days. The rats were killed at age 19-20 days. We observed
      decreased myelin staining in the external capsule, axonal degeneration in white
      matter, evidence of glial cell death in the white matter, and reactive
      astrogliosis in the frontal cortex. We did not detect myelin vacuolation. These
      findings indicate that vigabatrin can have adverse and potentially irreversible
      effects on the developing rat brain. The mechanism of damage could be direct
      toxicity of vigabatrin or an indirect effect mediated through elevated GABA
      levels. Vigabatrin has been recommended as a treatment for some forms of
      childhood epilepsy; therefore, further studies are needed to assess the risks in
      children.

PMID- 9168840
TI  - NMDA receptor overstimulation triggers a prolonged wave of immediate early gene
      expression: relationship to excitotoxicity.
AB  - Exposure of the rodent striatum to quinolinic acid (QA, N-methyl-D-aspartate
      receptor agonist) induces immediate early gene (IEG; c-fos, c-jun, jun-B,
      zif/268) expression that may extend 12-24 h after injection. In order to
      determine the specificity of the prolonged IEG response to the QA injection, the
      temporal pattern of c-fos mRNA expression was examined during the first 4 h after
      administration of saline or QA (40 micrograms). As early as 30 min after
      intrastriatal injection, both saline and QA increased c-fos mRNA levels. In the
      saline group, this increase in IEG expression was only transient and returned to
      baseline by 1 h. In contrast, c-fos mRNA levels within QA-injected animals
      continued to rise significantly at 1 and 4 h. In a second experiment, rats
      received 4 ng to 40-micrograms injections of QA followed by sacrifice at 6 h to
      determine if increasing QA doses caused the appearance of the prolonged IEG
      response phase. The prolonged IEG response was evident at 6 h only in animal
      groups that received higher dose ranges (4-40 micrograms) of QA. A final
      experiment was undertaken to determine if blockage of NMDA receptor stimulation
      would also inhibit the prolonged IEG response at 6 h in relationship to neuronal
      sparing evidenced at 24 h post-QA injection. The NMDA receptor antagonist, MK
      801, blocked the prolonged IEG response at 6 h following QA (40 micrograms)
      injection while also preventing striatal neuropeptide mRNA decline by 24 h.
      Delaying the MK-801 administration for 1-2 h post-QA injection revealed that the
      intensity of the prolonged IEG mRNA response may be predictive of neuronal demise
      within the QA lesion site. These results suggest that prolonged IEG expression is
      associated with QA excitotoxicity of the rodent striatum and subsequent neuronal
      degeneration.

PMID- 9168841
TI  - Huntington's disease: N-methyl-D-aspartate receptor coagonist glycine is
      increased in platelets.
AB  - Experiments in vertebrates and striatal tissue cultures have provided evidence
      for a neuroexcitotoxic cause for the neurodegeneration in Huntington's disease
      (HD), via N-methyl-D-aspartate (NMDA) receptors. Glycine in vitro increases the
      response of NMDA receptors to its agonists via the NMDA receptor-associated
      glycine receptor, and the same effect has been observed in vivo. Significantly
      increased levels of glycine have previously been found in the cerebrospinal fluid
      of patients with HD. In this present study glycine was measured in platelets and
      plasma of patients with HD and in controls by high-pressure liquid
      chromatography. Mean glycine concentration was significantly increased (P < or =
      0.01) in platelets in HD compared to controls, though plasma glycine was normal.
      A possible role for glycine in the pathogenesis of HD, based on the
      excitotoxicity hypothesis of HD, is discussed.

PMID- 9168842
TI  - Postprandial changes in superoxide dismutase activity in subjects with Gilles de
      la Tourette syndrome and controls.
AB  - Erythrocyte measures of copper-zinc superoxide dismutase (CuZnSOD) were performed
      on 11 subjects with a clinical diagnosis of Gilles de la Tourette syndrome (GTS)
      and 6 healthy controls at specified intervals throughout the day. There were no
      significant differences between GTS subjects and controls but in both subjects
      and controls there was a significant increase in SOD, 75 min postprandially,
      which decreased to baseline 135 min postprandially. This has implications for the
      timing of biological samples in future studies of SOD. Possible reasons for the
      increase are discussed.

PMID- 9168843
TI  - Enhancement of the behavioral response to apomorphine administration following
      repeated treatment in the 6-hydroxydopamine-lesioned rat is temporally correlated
      with a rise in striatal preproenkephalin-B, but not preproenkephalin-A, gene
      expression.
AB  - Repeated dopamine receptor stimulation in the 6-hydroxydopamine (6-OHDA)-lesioned
      rat produces a marked enhancement in the behavioral response to a given dose of
      dopamine agonist. Such treatment also increases the synthesis of preproenkephalin
      B (PPE-B) throughout the striatum and preproenkephalin-A (PPE-A) rostrally. To
      examine the relationship between these changes, 6-OHDA-lesioned rats were treated
      with apomorphine (5 mg/kg) twice-daily. Between 0.5 and 7 days treatment,
      behavior was monitored and the levels of PPE-A and PPE-B mRNA were determined by
      in situ hybridization. A single injection of apomorphine induced a well-known
      rotational response contraversive to the lesion (314 +/- 22 rotations h-1).
      However, with repeated injection, the response to apomorphine was markedly
      enhanced, being significantly higher on Days 3 (704 +/- 60 rotations h-1), 5
      (1354 +/- 104 rotations h-1), and 7 (1680 +/- 117 rotations h-1). In the lesioned
      caudate-putamen, but not in the nucleus accumbens, PPE-B expression rose in a
      manner that was temporally correlated with the enhanced locomotor response to
      apomorphine. PPE-A expression in the lesioned striatum, significantly increased
      only after 7 days treatment, did not correlate with the behavioral response. In
      conclusion, PPE-B may contribute to the development of behavioral
      supersensitivity following repeated dopamine-replacement therapy in animal models
      of Parkinson's disease.

PMID- 9168844
TI  - PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie.
AB  - The present study investigated the relationship among PrP deposition, microglial
      activation, vacuolation, and neuronal death in the hippocampus of the 301V/VM
      murine scrapie model (mean incubation period 117 +/- 1 days). PrP deposition was
      first detected after 30 days and microglial activation after 60 days. Vacuolation
      in the CA1 and CA2 pyramidal layer was present from 90 days onward. Only
      occasional in situ end labeling (ISEL)-positive neurons were present in the
      hippocampus of scrapie-infected mice from 75 days postinoculation (d.p.i.),
      except at 105 d.p.i. when relatively large numbers of apoptotic, ISEL-positive
      neurons in the CA1 hippocampal region were observed. Terminally ill animals
      showed almost complete loss of CA1 pyramidal neurons. Electron microscopy of the
      CA1 region at 105 days confirmed that these neurons were dying by apoptosis.
      These data suggest that microglial activation in scrapie is a response to
      abnormal PrP deposition rather than a response to neuronal cell loss.

PMID- 9168845
TI  - New insights into the pathogenesis and management of steroid-resistant asthma.
AB  - A population of difficult-to-control asthmatics exists who, despite high-dose
      daily GC therapy, continue to display evidence for active disease. This group has
      been termed steroid resistant since they fail to adequately respond to aggressive
      courses of high-dose oral and inhaled GC therapy. Persistent immune activation
      and airway inflammation which to varying degrees is resistant to GC therapy
      appears to define the immunological abnormality underlying SR asthma. Recent
      studies utilizing molecular biological techniques have identified both ligand-
      and DNA-binding defects that could possibly account for steroid resistance at a
      molecular level. The evaluation of the SR asthmatic must be comprehensive in its
      scope as several confounding factors can contribute to this symptom complex.
      Among others, these include poor compliance, improper medication technique,
      inadequate anti-inflammatory therapy, unrecognized contributing diseases,
      incorrect diagnoses, environmental factors, and psychosocial disturbances. The
      management of the SR asthmatic is challenging, and every attempt should be made
      to maximize conventional therapy in these patients prior to embarking on
      alternative therapies as all of the alternative anti
      inflammatory/immunomodulatory modalities are associated with significant toxicity
      or cost. Second-generation inhaled GC therapy, methotrexate, cyclosporine, IVIG,
      and leukotriene antagonists are potential alternative therapies, and although
      they remain viable options, they have been used in small numbers, and for short
      periods of time, and fail to result in long-term remissions. Although much
      insight into the pathogenesis of SR asthma has been gained, several issues remain
      unresolved. Ongoing airway inflammation is thought to contribute to steroid
      resistance, but at present, we have no standard method of determining the degree
      of inflammation. The incorporation of bronchoscopy with transbronchial biopsy has
      the potential to provide the greatest amount of information regarding the
      presence or absence of ongoing airway inflammation, but the invasive nature of
      the procedure precludes its use in pediatric patients and the most severe adult
      asthmatics. Large multicenter, placebo-controlled studies evaluating the
      available alternative therapies that incorporate markers of airway inflammation
      are needed, as are studies that evaluate these therapies over longer periods of
      time. It is hoped that by better understanding the mechanisms involved and the
      natural history of the SR asthmatic, specific treatment modalities will be
      developed for this challenging group of severe asthmatics.

PMID- 9168846
TI  - Anti-interleukin-4 inhibits immunoglobulin E production in a murine model of
      atopic asthma.
AB  - Immunoglobulin E (IgE) plays an important role in allergy, acting as an
      initiating factor and being involved in its persistence and exacerbations. As
      interleukin-4 (IL-4) is critical in IgE synthesis, we propose that treatment of
      mice with monoclonal anti-IL-4 (11B11) prior to active sensitization with
      ovalbumin will inhibit IgE synthesis, therefore arresting the allergic process at
      an early stage. Mice treated with 11B11 and sensitized with saline or ovalbumin
      had significantly less serum IgE than their respective control groups which were
      treated with saline (p < 0.05). This study suggests that anti-IL-4 may be a
      prophylactic agent in asthma and allergic disease.

PMID- 9168847
TI  - Assessing asthma management from interviews of patients and family physicians.
AB  - Directed self-care is recommended in asthma. Adequate patient education and
      follow-up are nevertheless necessary to optimize outcomes. We compared the
      agreement between detailed information on asthma history and management,
      collected from the patient and the family physician, to validate the files of
      physicians and to assess patients' knowledge, attitude, and behavior concerning
      asthma. A sample of 54 asthma patients were interviewed in detail about use of
      medications and self-care practice; 36 family physicians (FPs) were interviewed
      concerning asthma therapy, history, and attitudes of the same patients. Forty
      eight percent of the patients expressed negative attitudes toward inhaled
      corticosteroids, for reasons of safety or lack of efficacy. Less than 20% of the
      patients made regular use of a peak flow meter. Eighty-three percent of the
      patients usually obtained prescriptions for asthma therapy from their FP, but on
      average, only 40% of these prescriptions were provided during visits specific to
      asthma. FPs were not optimally informed of actual treatments and outcomes and had
      poor perception of patients' attitudes toward treatment. Nonetheless, in about
      30% of the patients, FPs identified risk factors for adverse outcome, such as
      depression and family conflicts. A majority of interviewed patients had a
      negative perception of anti-inflammatory therapy, specifically relating to issues
      of safety and efficacy. Peak flow meters were seldom used and therapy was
      commonly prescribed outside visits specific to asthma. Despite being centrally
      involved in the care of asthma patients, FP did not optimally assess therapy and
      outcomes. The findings suggest suboptimal education and health status in this
      asthma population.

PMID- 9168848
TI  - Roxithromycin attenuates acid-induced cough and water-induced bronchoconstriction
      in children with asthma.
AB  - In the present study, we evaluated the effect of roxithromycin, a semisynthetic
      macrolide antibiotic, on the cough response to inhaled acetic acid (AA) and on
      the bronchoconstriction induced by ultrasonically nebulized distilled water
      (UNDW) in children with asthma. Ten hospitalized asthmatic children (8 boys and 2
      girls, mean +/- SEM age 12.6 +/- 0.4 years) were enrolled in this study. They
      were treated with 150 mg of roxithromycin once a day orally for 8 weeks without
      any side effects. All the patients underwent AA inhalation challenge before and
      2, 4, and 8 weeks after the administration of roxithromycin. Seven of the 10
      patients, who had a fall in FEV1 of at least 20% after UNDW inhalation, underwent
      UNDW inhalation challege at the same time. The cough threshold values, the lowest
      concentrations of AA eliciting coughs, and UNDW provocative dose producing a 20%
      fall in FEV1 (UNDW PD20) values 4 or 8 weeks after the administration of
      roxithromycin increased significantly over the initial values (p < 0.05). No
      significant change was observed in baseline FEV1 or serum theophylline
      concentrations throughout the study. These results support the notion that
      administration of roxithromycin may have favorable results in the treatment of
      childhood asthma.

PMID- 9168849
TI  - Smoking and asthma among 23-year-olds.
AB  - Participants in a longitudinal cohort study (the National Child Development
      Study) were asked, at the age of 23, about their smoking habits and asthmatic
      experiences since 16 years of age. Of the total sample (n = 8860) 10.8% reported
      smoking cigarettes, and the percentages were very similar in the two sexes
      although males tended to be heavier smokers. There was an association between
      asthma and smoking; more than expected of those reported as having asthma at any
      age had smoked, and of those with asthma since 16 years of age more reported
      smoking than expected by chance. In addition, all who report asthma at any time
      since the age of 16 are overrepresented among those who report current smoking (p
      < 0.001). Those reporting asthma since 16 are more likely to be living with
      others who smoke, and their spouses or partners were more likely to be heavy
      smokers (30+ cigarettes per day). In addition, in more than the expected number
      of homes where asthmatics live, there are others who smoke (p < 0.003).

PMID- 9168850
TI  - Impact of fluticasone propionate powder on health-related quality of life in
      patients with moderate asthma.
AB  - Because biological indicators alone do not adequately represent the comprehensive
      health status of a patient with asthma, we also assessed patients' health-related
      quality of life (HRQOL) in a randomized, double-blind, placebo-controlled study
      of the effects of the inhaled corticosteroid fluticasone propionate (FP). A total
      of 342 patients with moderate asthma were treated twice daily for 12 weeks with
      FP powder (50, 100, or 250 micrograms) or placebo. At regular intervals, patients
      completed the Medical Outcomes Study Short Form-36, acute version (SF-36A), a
      general health status questionnaire measuring eight dimensions of HRQOL; the 20
      item Living with Asthma (LWA-20) questionnaire, a disease-specific instrument
      measuring HRQOL; and three additional questions related to sleep loss and number
      of nighttime awakenings. Each of the three FP groups compared with placebo had
      significantly higher scores at study endpoint on the Physical Functioning (p <
      0.001) and Role-Physical (p < or = 0.0001) dimensions of the SF-36A; the FP 100-
      or 250-micrograms groups compared with placebo also had significantly higher
      scores on General Health Perceptions (p < 0.03), Vitality (p < 0.007), and Mental
      Health (p < 0.02). At endpoint, all three FP groups compared with placebo had
      significantly better scores on the LWA questionnaire (p < 0.05) and on the sleep
      related items (p < 0.0001). These data, collected using both a general health
      status questionnaire and an asthma-specific questionnaire, demonstrate that
      fluticasone propionate powder can improve HRQOL in patients with mild-to-moderate
      asthma.

PMID- 9168851
TI  - Distribution of IgE and IgG antibody levels against house dust mites in
      schoolchildren, and their relation with asthma.
AB  - Although asthmatic patients are known to have increased levels of IgG antibody
      against house dust mite (HDM), it is not clear whether or not the presence of HDM
      specific IgG antibody is associated with the etiological mechanism of asthma. To
      address this problem, we evaluated the relationship between HDM-specific IgG
      antibody levels and incidence of asthma in a general pediatric population. IgE
      and IgG antibody levels against Dermatophagoides farinae (Df) were examined by
      RAST and ELISA in a total of 722 randomly selected schoolchildren including 26
      subjects with asthma, and the relative prevalence rates of asthma in this
      population were evaluated in relation to both Df-specific IgE and IgG levels. The
      incidence of asthma correlated not only with levels of Df-specific IgE, but also
      with those of Df-specific IgG. There was a significant correlation between Df
      specific IgE and IgG levels both in the total population and in the asthmatic
      children. Because IgG and IgE responses occurred in parallel in this population,
      the clinical significance of HDM-specific IgG anti-body remains unclear. However,
      our findings have suggested that clinical expression of asthma in children is
      primarily dependent on their capacity to mount a immune response to HDM, which
      includes both IgE and IgG responses.

PMID- 9168852
TI  - Characteristics of predominantly nonwhite patients with frequent hospitalizations
      for acute asthma in Chicago.
AB  - The purpose of this study was to determine the characteristics of predominantly
      nonwhite patients with recurrent visits to the emergency department (ED) and
      admissions to an inner-city hospital in Chicago for acute asthma. Over a 21-month
      period, two groups of age and gender-matched individuals with asthma seen at the
      University of Illinois at Chicago Medical Center were studied: group I included
      26 patients with frequent visits to the ED and no more than one admission for
      acute asthma/year; and group II included 28 patients with recurrent visits to the
      ED and two or more admissions for acute asthma/year. We found that 70% of all
      patients (38/54) were females and 72% (39/54) were African-Americans. The latter
      predominated in group II (25/28; 89%). There were no significant differences in
      public aid recipients, baseline FEV1, type of antiasthma medications used, and
      illicit drug use between the two groups. However, group II reported more asthma
      onset before the age of 11 years and used higher daily doses of inhaled
      corticosteroids than group I (p < 0.05). The average duration of hospital stay in
      group II was significantly longer (3.3 +/- 0.4 days vs. 2.4 +/- 0.3 days,
      respectively, mean +/- SEM, p < 0.05), and the average cost per hospitalization
      in group II significantly exceeded that of group I ($5122 +/- $590 vs. $3740 +/-
      $450, respectively, p < 0.05). We conclude that African-American females are seen
      more frequently in the ED for acute asthma and admitted to the hospital in
      Chicago. They develop asthma before the age of 11 years, use higher daily doses
      of inhaled corticosteroids, and contribute significantly to the high cost of
      asthma care.

PMID- 9168853
TI  - Importance of selected inhaler characteristics and acceptance of a new breath
      actuated powder inhalation device.
AB  - The degree of patient comfort and satisfaction with an inhaler can have an
      important effect on compliance with asthma treatment and, hence, therapeutic
      success. The objective of this study was to assess, from the patient's
      perspective, the importance of various inhaler characteristics and then evaluate
      patient satisfaction with a new breath-actuated powder inhaler (Diskhaler) based
      on those characteristics. Self-administered patient satisfaction questionnaires
      were completed as part of a randomized, double-blind, placebo-controlled study of
      fluticasone propionate powder in the treatment of asthma. At baseline, patients
      rated the importance of five inhaler characteristics (convenient to carry,
      durability, easy to load, easy to hold and operate, and easy to clean). Following
      exposure to the Diskhaler over a period of 8 weeks, patients rated the inhaler on
      those same characteristics. They also rated their comfort using the inhaler and
      their overall satisfaction with the inhaler. Data were available from 274
      patients, the majority of whom expressed a high or very high level of
      satisfaction with the Diskhaler on each of the five characteristics. These
      ratings were congruent with their ratings of the importance of those same
      characteristics; 80-90% rated "convenient to carry," "durability," "easy to
      load," and "easy to hold and operate" as important or very important
      characteristics for an inhaler, while "easy to clean" was considered somewhat
      less important, with 63% rating this characteristic as important or very
      important. Following the initial exposure to the Diskhaler, 67% of patients were
      comfortable or very comfortable with the inhaler; that percentage increased to
      79% after 8 weeks of use. Following 2 and 8 weeks of use, 61 and 62%,
      respectively, were satisfied or very satisfied with the Diskhaler. In general,
      satisfaction ratings were not affected by treatment, indicating that patients
      were evaluating only the inhaler and not the efficacy of the study drug they
      received. This study helped to identify which selected inhaler characteristics
      are most important to patients with asthma. The Diskhaler inhaler performed well
      on those characteristics deemed important to the patients. From their first
      exposure to the Diskhaler, patients were comfortable using the device, and this
      overall acceptance of the inhaler was maintained throughout the study.

PMID- 9168854
TI  - A minimal response to albuterol challenge does not exclude a diagnosis of asthma.

PMID- 9168855
TI  - Molecular approaches to oral therapeutics: dentistry in the next millennium?

PMID- 9168856
TI  - Chilton, Fertig, Fleiss, and the Task Force on Design and Analysis in Dental and
      Oral Research.

PMID- 9168857
TI  - Localization and expression of CSF-1 receptor in rat dental follicle cells.
AB  - Colony-stimulating factor-1 (CSF-1) accelerates tooth eruption in rats and is
      localized in the dental follicle, a loose connective tissue sac that is necessary
      for eruption to occur. CSF-1 enhances the cellular events that occur in the
      follicle prior to eruption--namely, an influx of monocytes into the follicle
      early post-natally to form the osteoclasts needed to resorb bone for the eruption
      pathway. Because CSF-1 levels are at a peak at day 3 post-natally, and because
      CSF-1 has an autocrine effect on its own gene expression, the question remains as
      to what causes the subsequent decline in CSF-1 protein and mRNA after day 3 post
      natally. To determine if the autocrine effect is inhibited through the CSF-1
      receptor, analysis of the CSF-1 receptor mRNA levels in cultured dental follicle
      cells reveals that high concentrations of CSF-1 reduce the gene expression of the
      CSF-1 receptor. Interleukin 1 alpha, a molecule that enhances CSF-1 gene
      expression, has no effect on CSF-1 receptor mRNA levels. Immunostaining for the
      CSF-1 receptor protein shows that it is present in the dental follicle early post
      natally and is either absent or greatly reduced by day 10 post-natally. Earlier
      studies showed that the mRNA levels of the CSF-1 receptor also parallel this time
      course. Thus, the above results suggest that the feedback inhibition of the
      autocrine effect of CSF-1 on its own expression is through the effect of CSF-1
      inhibiting the translation and transcription of its receptor. In turn, these
      molecular interactions possibly regulate the cellular events that occur in the
      follicle prior to and during eruption.

PMID- 9168858
TI  - Expression of heparan sulphate and small dermatan/chondroitin sulphate
      proteoglycans in chronically inflamed human periodontium.
AB  - Proteoglycans (PGs) function in regulating aspects of cell behavior, such as
      proliferation, adhesion, and migration. In this report, we investigated the
      localization of three heparan sulphate PGs (basement membrane [BM] heparan
      sulphate PG, CD44, and syndecan-1) and two small dermatan/chondroitin sulphate
      PGs (decorin and biglycan) in chronically inflamed human periodontium. Frozen
      sections were analyzed by immunofluorescence microscopy. In inflamed tissue, BM
      heparan sulphate PG showed reduced immunostaining in subepithelial and
      subendothelial basement membrane. Loss of CD44 and syndecan-1 was common in
      epithelial cells of inflamed periodontal tissue. Suprabasal keratinocytes of
      epithelium expressed involucrin, a cornified envelope protein and marker for
      epithelial differentiation, while the expression of syndecan-1 was weak or
      absent. In contrast, expression of the mesenchymal variant of CD44 and syndecan-1
      was strong in infiltrating lymphocytes. Small dermatan/chondroitin sulphate PGs,
      decorin and biglycan, were also present in markedly reduced amounts in the
      periodontal connective tissue in chronic inflammation. In addition, decorin
      localized in the connective tissue along short rod-like structures. The results
      suggest that proteoglycan-dependent intercellular adhesion of keratinocytes is
      decreased and that adhesion of lymphocytes to matrix molecules via cell surface
      PGs increased in chronic inflammation. Disappearance of adhesion-modulating small
      dermatan/chondroitin sulphate PGs may further regulate cell migration in inflamed
      periodontium.

PMID- 9168859
TI  - Activation and novel processing of matrix metalloproteinases by a thiol
      proteinase from the oral anaerobe Porphyromonas gingivalis.
AB  - A critical outcome of periodontal disease is degradation of the collagenous
      periodontal ligament that connects teeth to bone in the dental arch. Periodontal
      diseases occur in response to bacterial colonization of the teeth, but their
      molecular pathogenesis is still speculative. One family of enzymes, known as the
      matrix metalloproteinases (MMPs), has been implicated in the degradation of the
      periodontal ligament. MMPs, which are also suspected to play a role in many other
      physiologic and pathologic remodeling processes, can be secreted by epithelial
      cells surrounding the teeth and are found in relative abundance in tissues and
      fluids near periodontally diseased sites. Since most MMPs are secreted as
      inactive zymogens which may be activated by limited proteolysis, it has been
      suggested that proteinases expressed by the infecting periodontal pathogens might
      activate latent host MMPs to initiate or accelerate degradation of the
      collegenous periodontal ligament. The aim of this work was to examine
      interactions between purified host MMPs and bacterial proteinase. In this
      article, we demonstrate that a proteinase isolated from the periodontopathogen
      Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze
      the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated
      to result from initial hydrolysis within their propeptide. Also, for MMP-1 and
      MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine
      residue at a previously unreported site which, for both MMPs, is one residue NH2
      terminal to the known autocatalytic cleavage site. These data describe a mode of
      virulence for the periodontopathogen Porphyromonas gingivalis that involves
      activation of host-degradative enzymes.

PMID- 9168860
TI  - Oral infections in home-living elderly patients admitted to an acute geriatric
      ward.
AB  - Little is known about the oral health of the frail and home-living elderly. The
      effects of dentogenic infections on the general condition of the elderly are also
      unknown. We therefore set out to investigate 191 elderly patients referred to an
      acute geriatric hospital due to sudden worsening of their general health. The
      patients' mean age was 81.2 +/- 6.4 years (range, 67 to 96 years), and they had
      lived at home before hospitalization. The patients were examined and their
      diagnoses set by a team of physicians. The dentist's examination was also made
      bedside. Panoramic x-rays were taken for those who were able to stand (n = 148).
      Particular attention was paid to the occurrence of dental infection foci and
      systemic infection parameters of blood. Only patients free from other than dental
      infections were included in the statistical analyses (n = 184). Panoramic x-rays
      revealed dentogenic infection foci in 71.1% of the dentate patients. Periodontal
      condition was poor in 96.2% of the patients (CPI score, 2 to 4). All infection
      parameters were high in patients with high periodontal treatment need, but the
      differences were not statistically significant. Neither were there statistically
      significant correlations between the number of dentogenic infection foci recorded
      from the radiographs and infection parameters of blood. More of the edentulous
      patients had positive salivary yeast counts than did the dentate patients (84.4%
      vs. 66.1%; P < 0.05). No correlation was found between the main systemic
      diagnoses and dental infections. Since the prevalence of dentogenic infection
      foci in our subjects was high, and they did not cause marked increase in the
      hematological infection parameters investigated, it seems clear that
      geriatricians should refer their patients for dental examinations. Although our
      patients represent the home-living elderly population in a Nordic country with a
      high standard of living and good medical care, dental care had been neglected
      regardless of the patients' systemic disease.

PMID- 9168861
TI  - Oral mucosal smokeless tobacco lesions among adolescents in the United States.
AB  - The presence of oral smokeless tobacco lesions among adolescents may be an early
      indicator of increased risk for oral cancers. Data from the 1986-1987 National
      Survey of Oral Health in US School Children were used to examine the cross
      sectional relationship between the use of tobacco and alcohol and the presence of
      white or whitish oral soft-tissue lesions. The sample included 17,027
      schoolchildren (aged 12 to 17 years) who provided information on the use of
      snuff, chewing tobacco, cigarettes, and alcohol and who received oral clinical
      examinations. Smokeless tobacco lesions were detected in 1.5% of students
      (projects to about 300,000 nationally), including 2.9% of males and 0.1% of
      females. These lesions were more prevalent among whites (2.0%) than among African
      Americans (0.2%) or Hispanics (0.8%). Modeling with multivariate logistic
      regression revealed that, among white males, current snuff use was the strongest
      correlate of lesions [odds ratio (OR) = 18.4; 95% confidence interval (CI) = 8.5
      39.8], followed by current chewing tobacco use [OR = 2.5; 95% CI = 1.3-5.0].
      Lesions were strongly associated with duration, monthly frequency, and daily
      minutes of use of snuff and chewing tobacco. These data suggest that snuff may be
      a stronger risk factor than chewing tobacco for smokeless tobacco lesions, but
      the use of either of these forms of oral tobacco exhibits a dose-response
      relationship with the occurrence of lesions. We found little evidence that the
      use of alcohol or cigarettes may increase the risk of smokeless tobacco lesions.
      Preventing smokeless tobacco lesions and their possible malignant transformation
      may be best accomplished among adolescents by preventing the use of snuff and
      chewing tobacco.

PMID- 9168862
TI  - Changes in self-reported dental anxiety in New Zealand adolescents from ages 15
      to 18 years.
AB  - Little is understood of the natural history of dental anxiety. The aim of this
      study was to examine three-year changes in self-reported dental anxiety among
      adolescent participants in the Dunedin Multidisciplinary Health and Development
      Study. Dental anxiety was estimated at ages 15 and 18 by means of the Corah
      Dental Anxiety Scale (DAS). A DAS score of 13+ defined high dental anxiety.
      Participants were assigned to one of four dental-anxiety study groups (Chronic,
      Incident, Remitted, or Never) on the basis of changes in reported level of
      anxiety from ages 15 to 18. Results are reported for the 691 participants who
      completed the DAS at both ages. The sample's overall dental anxiety score
      decreased significantly from age 15 (mean, 8.79) to 18 (8.52) (paired t test, t =
      2.37; P < 0.05). The Chronic and Never groups had small negative DAS increments,
      the Incident group showed a substantial positive increment, and the Remitted
      group recorded an even larger negative increment. Multivariate analysis showed
      that the DAS score at age 15 was the sole predictor of the change in DAS score
      for the Chronic and Remitted groups, and was a co-predictor for the Incident and
      Never groups. An episodic dental visiting pattern was a strong predictor of a
      positive change in DAS score for the Incident group; and for the Never group, a
      higher DMFS score at age 15 predicted a positive change in DAS score at 18, but
      being female was predictive of a decrement. This study indicates lower stability
      of dental anxiety in late adolescence than has been reported from other age
      groups.

PMID- 9168863
TI  - Three-year changes in self-perceived oral health status in an older Canadian
      population.
AB  - Although change is a central goal of oral health care interventions, little
      attention has yet been paid to change in self-perceptions of oral health status.
      This is an important omission, given the current emphasis on assessing health
      outcomes. This paper reports the results of a study which examined changes over a
      period of three years in self-perceived oral health among 611 community-dwelling
      Canadians aged 50 years and over. Change in self-perceptions was measured by
      means of a global transition item and change scores derived from repeat
      administrations of four subjective oral health status indicators. Overall, 20.5%
      reported that their oral health had deteriorated over the three-year observation
      period, 68.5% that it had remained the same, and 10.5% that it had improved.
      There was a significant association between these global change categories and
      change scores for the four subjective indicators. Because of the small number of
      edentulous subjects, the analysis of baseline characteristics predicting change
      was confined to dentate subjects. Bivariate and logistic regression analyses were
      used to compare the two groups reporting change with those whose oral health
      status remained stable over the observation period. The results suggest that,
      when compared with this reference group, those who deteriorated and those who
      improved were similar in some respects but distinct in others. Those who improved
      appeared to have specific oral conditions at baseline causing pain. Those who
      deteriorated had poor oral health in general and came from more disadvantaged
      backgrounds. However, the explanatory power of logistic regression models
      predicting change in self-perceived oral health was poor when judged in terms of
      model sensitivities. This was to be expected, given that the models did not
      include variables documenting the incidence of disease, receipt of dental care,
      or changes in social and personal circumstances over the observation period.

PMID- 9168864
TI  - Why do shear bond tests pull out dentin?
AB  - It is widely accepted that a dentin shear bond test which pulls out dentin must
      mean that the adhesive strength is superior to the cohesive strength of the
      dentin. Using numerical modeling techniques, Van Noort et al. (1988, 1989) and
      DeHoff et al. (1995) alerted the scientific community that there were massive
      stress concentrations in the familiar dentin bond test. It is not inconceivable
      that these localized high tensile stresses could initiate cracks which diverge
      monolithically into dentin, leaving the interface unchallenged. To test this
      hypothesis, we developed a failure accumulation simulation program which
      determined localized failure interactively "on the fly" with a finite element
      solver, and also included brittle behavior, adhesive and cohesive failure,
      stochastic response, and dynamic remeshing. All of the familiar dentin bond
      variables were included in the simulation. A parallel experimental dentin bond
      test validation was run, and the fractography was examined in the scanning
      electron microscope for mode of failure. The simulation confirmed the tensile
      monolithic fracture hypothesis. It is also confirmed that dentin pull-out was
      partly due to the biomechanics of the test and did not necessarily mean superior
      adhesive strength or even that the cohesive strength of the dentin was reduced.
      There is clear need for a new technology for the evaluation of biological
      interfaces, and the present work has shown the vital role of numerical modeling
      in the interpretation of such experimental procedures.

PMID- 9168865
TI  - Dissolution of mercury from dental amalgam at different pH values.
AB  - Dissolution of mercury from dental amalgam has been shown to be diminished by the
      formation of a tin oxide film on the surface of the mercury-rich gamma 1 phase
      (Marek, 1990b). Since tin oxides dissolve at low pH values (Deltombe et al.,
      1974), acidic conditions in the oral cavity may cause an increase in the mercury
      release. The purpose of this study was to determine the effect of acidity in the
      range of pH 1 to pH 8 on the rate of mercury dissolution in synthetic saliva from
      tin-free and tin-containing gamma 1 phase and two commercial dental amalgams. The
      tested hypothesis was that pH affects mercury dissolution only when a protective
      oxide film dissolves in an acidic environment. After exposures of the specimens
      for 2 hr or 24 hr in sealed glass bottles, the solutions were analyzed by
      flameless atomic absorption spectrophotometry for mercury and silver. The results
      have shown pH-independent mercury dissolution in the range of pH 3 to 8, and a
      much faster dissolution at pH 1. At all pH values, more mercury dissolved from
      the tin-free phase than from the tin-containing phase, and the rate of
      dissolution was lowest for the dental amalgams. The results were affected by the
      length of the test exposure. The pH independence in a wide range of pH values has
      been attributed to the atomic mechanism of mercury dissolution. The low rate of
      mercury dissolution from specimens containing tin has been explained by the
      formation of a barrier tin oxide film, which dissolved only at the lowest pH.
      Dissolution of silver at low pH values is believed to have accelerated
      dissolution of mercury from the tin-free gamma 1 phase. Variation of the
      dissolution rate with concentration of the dissolved species and kinetics of
      oxide film dissolution caused the effect of the exposure period.

PMID- 9168866
TI  - The association among occlusal contacts, clenching effort, and bite force
      distribution in man.
AB  - The contact area during habitual biting can vary according to the activity of the
      jaw musculature. Forceful masticatory muscle activity may also induce
      deformations of the dento-alveolar tissues and the supporting skeleton, yielding
      various tooth loads despite an apparently even distribution of tooth contacts. To
      investigate this variability, we measured bite forces simultaneously at multiple
      dental sites during maximum-effort clenching tasks. In each of four healthy
      adults with complete natural dentitions, four strain-gauge transducers in the
      right side of an acrylic maxillary appliance occluded with the lower canine,
      second premolar, and first and second molars. These, and matching contralateral
      contacts, were balanced by means of articulating paper and a force monitor (type
      F appliance). Bite forces were recorded when the subjects, without visual
      feedback, clenched maximally on the appliance. Similar recordings were made when
      contralateral molar and all contralateral contacts were removed (type R and type
      U appliances, respectively). Although the relation between individual forces
      often changed during the initial increase in force, it was generally constant
      around the maximum. The maximum forces at the four dental locations varied in
      distribution between subjects, but were characterized by posteriorly increasing
      forces. Forces in the anterior region (especially at the canine) significantly
      increased (up to 10 times) when clenching took place on unilateral contacts only
      (type U) as compared with fully balanced ones (type F). Bite force distribution
      thus changed with biting strength and the location of occlusal contacts.
      Increased force in the canine region during unilateral clenching seems related to
      the pattern of jaw muscle co-activation and the physical properties of the
      craniomandibular and dental supporting tissues which induce complex deformations
      of the lower jaw.

PMID- 9168867
TI  - Prenatal evaluation of fetal anomalies.
AB  - Advances in sonographic imaging have allowed for detailed examination of the
      fetus. A wide range of abnormalities of the fetal central nervous system, chest,
      gastrointestinal tract, genitourinary system, and skeleton are detectable by
      prenatal sonography. This article reviews the sonographic findings and prognostic
      implications of these abnormalities.

PMID- 9168868
TI  - Controversies in abdominal imaging.
AB  - Technologic improvement in ultrasound equipment, together with new clinical
      information, has altered the imaging of the abdomen in infants. Improvements in
      ultrasound equipment have allowed this to become the diagnostic test of choice
      for hypertrophic pyloric stenosis. Barium upper gastrointestinal radiography
      still remains the diagnostic test of choice for malrotation. New technologies for
      reduction of intussusception include air reduction and saline enemas with
      ultrasound monitoring. Controversies surrounding the different technologies and
      imaging strategies are discussed.

PMID- 9168869
TI  - Imaging children with acute right lower quadrant pain.
AB  - In summary, sonography is the primary modality for evaluating children with acute
      right lower quadrant pain. Sonography is particularly useful in the evaluation of
      children with suspected appendicitis in whom the clinical findings are equivocal,
      and in the evaluation of female children with suspected pelvic pathology.
      Findings at sonography should not supersede clinical judgement in patients who
      are believed to be at high clinical risk of having appendicitis on the basis of
      clinical signs and symptoms. Abdominal radiographs are helpful primarily if small
      bowel obstruction or perforation is suspected; CT is useful for evaluating
      complications of appendicitis and evaluating the postoperative patient.

PMID- 9168870
TI  - Imaging of developmental dysplasia of the hip.
AB  - Careful clinical examination remains the primary and most important way of
      diagnosing developmental dysplasia of the hip (DDH) in newborn infants. Repeated
      examinations during the first year are important to diagnose DDH subsequent to
      the newborn period. Sonography can detect cases of clinically silent DDH.
      Targeting high-risk infants for supplemental ultrasound screening at 4 to 6 weeks
      of age increases diagnosis of DDH and at significantly less expense than
      widespread screening. When sonography is not available, a pelvis radiograph at 3
      months should be obtained in high-risk infants. Sonography also is used to
      monitor hip position and acetabular development in children undergoing harness
      treatment. Computed tomography and magnetic resonance imaging are reserved for
      children with more severe dysplasia, often as preoperative studies to help
      orthopedic surgeons to select the appropriate procedure.

PMID- 9168871
TI  - Imaging of child abuse.
AB  - Diagnostic imaging plays a fundamental role in the evaluation of suspected
      physical abuse. Judicious application of modern imaging techniques to cases of
      suspected abuse aids in early and accurate diagnosis, leading to appropriate
      measures to protect all family members at risk of serious injury.

PMID- 9168872
TI  - Imaging the child with a limp.
AB  - A great many pathologic conditions can cause a child to limp. Prior to imaging,
      it is necessary to complete a thorough history and physical examination in order
      to limit the differential diagnosis to a few possible causes. The selection of
      imaging modalities should then be guided by the history and physical examination
      findings. Because of their sensitivity and specificity for detecting a wide range
      of bone pathology, radiographs should be obtained first. Plain radiographs often
      are diagnostic. The choice of sonography, CT, bone scintigraphy, or MR imaging is
      made while keeping in mind the strengths of each imaging modality.

PMID- 9168873
TI  - Magnetic resonance imaging of the cardiovascular system and airway.
AB  - Cardiovascular MR imaging is unique in its ability to combine anatomic,
      physiologic, and functional information in a single examination. Established
      applications in the pediatric population include the evaluation of the child with
      a suspected thoracic aortic arch anomaly, vascular compression of the airway,
      coarctation of the aorta, pulmonary arterial and venous abnormalities, and
      cardiac or paracardiac masses. The increasing availability of radiologists with
      the knowledge and commitment to cardiac imaging will allow this exciting
      technique to thrive in the future, to the benefit of our patients.

PMID- 9168874
TI  - Imaging of paranasal sinus disease.
AB  - Imaging plays an important role in the management of paranasal sinus disease in
      the pediatric population. An understanding of the advantages and disadvantages of
      available modalities enables the clinician to best utilize imaging resources.

PMID- 9168875
TI  - Diagnostic imaging in neuro-oncology.
AB  - Recent advances in imaging techniques, biologic characterization, and histologic
      classification have contributed to improving management of children with brain
      tumors. The overall prognosis of children with brain tumors nevertheless lags
      behind that of other pediatric oncologic diseases. This article reviews recent
      developments in tumor imaging.

PMID- 9168876
TI  - Diagnostic imaging in pediatric AIDS.
AB  - The manifestations of acquired immune deficiency syndrome (AIDS) in children are
      mainly secondary to opportunistic infection, lymphoproliferative diseases, and
      AIDS-related neoplasms. This article reviews the pathologic findings of various
      disorders afflicting children with AIDS and emphasizes the imaging of these
      disorders. Although many of the radiologic findings are not specific for a
      particular infection or neoplasm, the differential diagnostic possibilities for
      an abnormality can be narrowed down significantly with proper clinical
      correlation and knowledge of the imaging findings and pathologies specific to
      children with AIDS.

PMID- 9168877
TI  - Bone marrow transplantation in children. Imaging assessment of complications.
AB  - As the use of BMT increases for the treatment of a variety of malignant and
      nonmalignant diseases in children, awareness of the complications that can occur
      in these children is important. The imaging appearance of the complications that
      may occur in the central nervous system, paranasal sinus, lungs, abdomen, and
      pelvis in children following BMT have been reviewed. CT and MR imaging
      examination with the use of contrast material as indicated is important for
      defining pathology in the brain. Plain films should be supplemented with CT
      examination as needed to identify and characterize disease in the paranasal
      sinuses and lungs. Finally, the use of ultrasound and CT is crucial for defining
      complications that may occur in the abdomen and pelvis.

PMID- 9168878
TI  - Future directions in interventional pediatric radiology.
AB  - In conclusion, the explosion of interventional radiology and its impact on the
      pediatric patient have resulted in a completely new approach to the subspecialty
      of interventional pediatric radiology. The interventional radiologist has become
      an integral part of the management of patients and has become directly involved
      in the day-to-day care of patients. The use of interventional MR imaging recently
      has been described in clinical trial. Open-configuration magnets that allow full
      access to the patient and are equipped with instrument tracking systems provide
      an interactive environment in which biopsies, endoscopic procedures, and
      minimally invasive interventions or surgeries are performed. In addition, thermal
      ablation and image-based control of energy deposition also can be performed.
      Among these procedures, noninvasive MR-guided focused ultrasound ablation has the
      most promising future and may replace some conventional surgery. The merging of
      new and exciting technologies including MR, ultrasound, CT, and fluoroscopy into
      an environment in which both surgical and interventional radiologic procedures
      can be performed with image guidance is the basis of the operating room of the
      future. The role of the interventional radiologist as both the imager and
      interventionalist is central to this procedural environment; however, the
      interventional radiologist must accept all the responsibilities of imaging,
      therapy, patient care, and associated complications.

PMID- 9168879
TI  - Late promoter selection in the baculovirus gp64 envelope fusion protein gene.
AB  - The upstream promoter region of the Autographa californica multicapsid nuclear
      polyhedrosis virus (AcMNPV) gp64 gene contains five copies of TAAG, the conserved
      sequence found at the transcriptional initiation sites of almost all baculovirus
      late genes. In AcMNPV-infected Sf9 cells, late transcription initiation is
      detected from only two upstream TAAG sites and not from three downstream TAAG
      sites. To examine several models for preferential TAAG site utilization, we
      constructed a series of recombinant AcMNPV baculoviruses that contain promoter
      region sequences from the gp64 gene fused to a chloramphenicol acetyl transferase
      reporter gene. Promoter-reporter constructs were inserted in the polyhedrin
      locus. To test a scanning model in which TAAG sites are sequentially selected
      according to their location in the region, we generated recombinant viruses in
      which the highly transcribed sites were inactivated by point mutations.
      Transcription from the mutant promoter constructs was compared qualitatively and
      quantitatively to transcription from the wild-type gp64 promoter. Inactivation of
      the upstream TAAG sites did not result in increased transcription from the
      downstream TAAG sites, suggesting that immediate context, rather than position,
      determines promoter utilization. To test this hypothesis, we made a series of
      minimal promoter constructs containing decreasing quantities of the sequences
      immediately flanking one of the active gp64 TAAG sites. Reporter constructs
      containing a gp64 TAAG site and > or = 12 bp of flanking sequence on both sides
      were transcribed at near wild-type levels. Constructs with less flanking sequence
      (9 or 6 bp of flanking sequence) were accurately transcribed, but at
      substantially lower levels, and transcription was not detected from constructs
      containing only 3 bp of flanking sequence. These results suggest that nucleotides
      immediately flanking the TAAG site (4-6 bp) are necessary for basal promoter
      activity while additional flanking sequences (> or = 12 bp) are required for late
      promoter activation and regulation. To further examine late promoter selection,
      we constructed recombinant AcMNPV baculoviruses that contain heterologous late
      promoters from the gp64 gene of the related virus Orgyia pseudotsugata MNPV
      (OpMNPV). TAAG sites that serve as functional late promoters in OpMNPV were found
      to mediate transcription initiation at only basal levels in the context of the
      AcMNPV genome, suggesting that late promoter activation may be virus specific
      within the family Baculoviridae.

PMID- 9168880
TI  - The satellite RNA of barley yellow dwarf virus-RPV is supported by beet western
      yellows virus in dicotyledonous protoplasts and plants.
AB  - The subgroup II luteovirus barley yellow dwarf virus-RPV (BYDV-RPV) acts as a
      helper virus for a satellite RNA (satRPV RNA). The subgroup II luteovirus beet
      western yellows virus (BWYV) and the ST9-associated RNA (ST9a RNA), a BWYV
      associated RNA that encodes a polymerase similar to those of subgroup I
      luteoviruses, were assayed for their ability to support replication of satRPV
      RNA. SatRPV RNA was replicated in tobacco protoplasts in the presence of BWYV RNA
      or a mixture of BWYV plus the ST9a RNA, but not in the presence of ST9a RNA
      alone. ST9a RNA stimulated BWYV RNA accumulation which, in turn, increased the
      accumulation of satRPV RNA. SatRPV RNA was encapsidated in BWYV capsids primarily
      as circular monomers, which differs from the linear monomers found in BYDV (RPV +
      PAV) particles. SatRPV RNA was transmitted to Capsella bursa-pastoris plants by
      aphids only in the presence of BWYV and ST9a RNA. SatRPV RNA reduced accumulation
      of both BWYV helper and ST9a nonhelper RNAs in plants but did not affect
      symptoms. The replication of satRPV RNA only in the presence of subgroup II
      luteoviral RNAs but not in the presence of RNAs with subgroup I-like polymerase
      genes, in both monocotyledonous and dicotyledonous hosts, suggests that the
      specificity determinants of satRPV RNA replication are contained within the
      polymerase genes of supporting viruses rather than in structural genes or host
      plants.

PMID- 9168881
TI  - A hybrid baculovirus-T7 RNA polymerase system for recovery of an infectious virus
      from cDNA.
AB  - We established a hybrid baculovirus-T7 RNA polymerase system for transient
      expression in mammalian cells. Two recombinant baculoviruses carrying cDNA of
      bacteriophage T7 RNA polymerase, with or without a nuclear localization signal,
      under the control of a mammalian promoter were constructed. High level expression
      of T7 RNA polymerase was observed in various mammalian cell lines after infection
      with the recombinant baculoviruses. After transfection of plasmids containing the
      luciferase gene under the control of the T7 promoter, high luciferase activity
      was detected in cells infected with the recombinant baculoviruses. We also
      constructed a plasmid containing an entire cDNA clone of type 1 poliovirus under
      the T7 promoter. Two days after transfection of the plasmid into the cells
      infected with the recombinant baculoviruses, a high titer of poliovirus was
      recovered. The use of the recombinant baculoviruses did not cause any cytopathic
      effects even at a high multiplicity of infection. The lack of replication ability
      and low toxicity are the advantageous features of the hybrid baculovirus-T7
      polymerase system in comparison with the widely used vaccinia-T7 polymerase
      system for gene expression and recovery of infectious viruses from its cDNA.

PMID- 9168883
TI  - Host site selection for concerted integration by human immunodeficiency virus
      type-1 virions in vitro.
AB  - Host site selection for full-site integration by human immunodeficiency virus
      type-1 (HIV-1) intergrase (IN) from nonionic detergent-lysed virions was
      investigated. Linear retrovirus-like DNA (469 bp) possessing 3' OH recessed long
      terminal repeat termini was efficiently inserted by a bimolecular donor reaction
      into a supercoiled DNA target (2867 bp), producing the HIV-1 5-bp host site
      duplication. Sequence data were analyzed from 193 donor-target recombinants
      obtained from the linear 3.8-kb DNA product. The selection of host target sites
      appeared randomly distributed and was independent of lysis and assay conditions.
      The fidelity of the 5-bp duplications in comparison to other size duplications
      was highest (94%) with high-salt (300 mM NaCl) lysis of the virions and 60 mM
      NaCl for strand transfer using Mg2+ as the divalent cation. Base sequence
      analysis demonstrated some biases in the 5-bp duplications at the sites of strand
      transfer and at the immediate host sequences surrounding the duplications. In
      addition to the observed duplications, approximately 30% of the recombinants
      isolated from the linear 3.8-kb DNA product contained specific and repetitive
      small-size deletions. No deletions smaller that 17 bp were observed and the
      distance between the deletion sets had a periodicity of approximately 10 bp. The
      mechanisms involved in how HIV-1 IN produces the 5-bp duplications and the
      repetitive host site deletions are discussed.

PMID- 9168882
TI  - Amplification of recombinant adenoviral transgene products occurs by inhibition
      of histone deacetylase.
AB  - n-Butyrate (butyrate) has been shown to amplify transgene expression in cells
      infected with E1-defective adenoviruses. The present studies were undertaken in
      order to better define the actions of butyrate in the context of adenovirus gene
      expression, and to attempt to elucidate the mechanism by which butyrate mediates
      the transgene amplification. It was found that butyrate amplified viral transgene
      expression over a concentration range of 0.5-5 mM, and that the amplification
      required an exposure of 12-24 hr for maximal effect. Western blot analysis of
      representative viral proteins showed that butyrate treatment amplified DNA
      binding protein, but not fiber protein. A transient adenoviral replication system
      suggested that butyrate had a modest inhibitory effect on replication of the E1
      defective adenovirus. Use of a specific inhibitor of histone deacetylase,
      trichostatin A (TSA), reproduced the amplification of the viral transgene product
      achieved with the butyrate. In contrast, adenoviral transgene expression could
      not be amplified by TSA treatment in a cell line known to have a TSA-resistant
      histone deacetylase. Butyrate amplified steady-state gene expression of the viral
      transgene, but had no detectable effects on either DNA-binding protein or fiber
      steady-state gene expression. Nuclear run-off experiments showed that both
      butyrate and TSA caused an increase in the viral transgene transcription. It was
      concluded that inhibitors of histone deacetylase amplify adenoviral transgene
      expression at the transcriptional level.

PMID- 9168884
TI  - Mutations affecting lysine-35 of gpNu1, the small subunit of bacteriophage lambda
      terminase, alter the strength and specificity of holoterminase interactions with
      DNA.
AB  - The small subunit of lambda terminase, gpNu1, contains a low-affinity ATPase
      activity that is stimulated by nonspecific dsDNA. The location of the gpNu1
      ATPase center is suggested by a sequence match between gpNu1 (29-VLRGGGKG-36) and
      the phosphate-binding loop, or P-loop (GXXXXGKT/S), of known ATPase. The proposed
      P-loop of gpNu1 is just downstream of a putative helix-turn-helix DNA-binding
      motif, located between residues 5 and 24. Published work has shown that changing
      lysine-35 of the proposed P-loop of gpNu1 alters the response of the ATPase
      activity to DNA, as follows. The changes gpNu1 k35A and gpNu1 K35D increase the
      level of DNA required for maximal stimulation of the gpNu1 ATPase by factors of 2
      and 10-fold, respectively. The maximally stimulated ATPase activities of the
      mutant enzymes are indistinguishable from that of the wild-type enzyme. In the
      present work, the effects of changing lysine-35 on the cos-cleavage and DNA
      packaging activities of terminase were examined. In vitro, the gpNu1 K35A enzyme
      cleaved cos as efficiently as the wild-type enzyme, but required a 2-fold
      increased level of substrate DNA for saturation, suggesting a slight reduction in
      DNA affinity. In a crude DNA-packaging system using cleaved lambda DNA as
      substrate, the gpNu1 K35A enzyme had a 10-fold defect. In vivo, lambda Nu1 K35A
      showed a 2-fold reduction in cos cleavage, but no packaged DNA was detected. The
      primary defect of the gpNu1 K35A enzyme was concluded to be in a post-cos
      cleavage step of DNA packaging. In in vitro cos-cleavage experiments, the gpNu1
      K35D enzyme had a 10-fold increased requirement for saturation by substrate DNA.
      Furthermore, the cos-cleavage activity of gpNu1 K35D enzyme was strongly
      inhibited by the presence of nonspecific DNA, indicating that the gpNu1 K35D
      enzyme is unable to discriminate effectively between cos and nonspecific DNA. No
      cos cleavage was observed in vivo for lambda Nu1 K35D, a result consistent with
      the discrimination defect found in vitro for the gpNu1 K35D enzyme. In a crude
      packaging system the gpNu1 K35D enzyme had a 200-fold defect; in a purified
      packaging system, the gpNu1 K35D enzyme was found to be unable to discriminate
      between lambda DNA and nonspecific phage T7 DNA, a result indicating that the
      gpNu1 K35D enzyme is also defective in discriminating between lambda DNA and
      nonspecific DNA during DNA packaging.

PMID- 9168885
TI  - Identification of regions in HIV-1 Nef required for efficient downregulation of
      cell surface CD4.
AB  - Downregulation of cell surface CD4 is a characteristic property of all lentiviral
      Nef proteins. We have used mutational analysis to define regions within HIV-1 Nef
      that are critical for this biological activity. Two discontinuous regions in Nef,
      extending approximately from residues 96 to 144 and from residues 175 to 186, are
      reported to be essential for efficient CD4 downregulation. Interestingly, these
      sequences coincide with two conserved regions of the Nef protein that are
      juxtaposed to form a single surface on the known structure of Nef. A third, more
      amino terminal conserved region in Nef, previously reported to be important for
      Nef enhancement of virion infectivity, was found to be largely dispensable for
      CD4 downregulation. These data raise the possibility that Nef may contain two
      structurally distinct functional domains, only one of which contributes to the
      CD4 downregulation phenotype.

PMID- 9168886
TI  - Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication.
AB  - Human cytomegalovirus is a herpesvirus that induces numerous cellular processes
      upon infection. Among these are activation of cyclin-dependent kinase 2, which
      regulates cell cycle progression in G1 and S phase. We report here that
      inhibition of cellular Cdk2 activity blocks HCMV replication. Inhibition of Cdk2
      activity by roscovitine inhibits HCMV DNA synthesis, production of infectious
      progeny, and late antigen expression in infected cells in a dose-dependent
      manner. HCMV replication is also inhibited by the expression of a Cdk2 dominant
      negative mutant, whereas expression of wild-type Cdk2 has no effect on viral
      replication. These data indicate that activation of cellular Cdk2 is necessary
      for HCMV replication.

PMID- 9168887
TI  - Cucumber mosaic virus is restricted from entering minor veins in transgenic
      tobacco exhibiting replicase-mediated resistance.
AB  - Transgenic tobacco plants expressing an altered form of the 2a replicase gene
      from cucumber mosaic virus (CMV) strain Fny exhibited a suppression of viral
      replication and restricted viral movement when inoculated mechanically or by
      insect vectors. Resistant plants could be infected, however, through a graft
      union with an infected nontransformed plant. The infectious entity moved quickly
      through intergrafts of resistant tissue, indicating that it could move without
      replicating in the vascular system. Viral replication continued to be suppressed
      in systemically infected transgenic portions of grafted plants, as demonstrated
      by the synthesis of lower levels of viral RNA than in systemically infected
      nontransformed portions of the same grafted plants. Cell-to-cell spread within
      this tissue also occurred much more slowly than in nontransformed tobacco. Young
      inoculated levels of transgenic-resistant plants exhibited limited cell-to-cell
      virus movement, revealed as chlorotic lesions, but no long-distance virus
      movement occurred. The results of in situ hybridization studies on these lesions
      indicated that CMV RNA does not traffic from bundle-sheath cells to vascular
      parenchyma or companion cells in chlorotic lesions on the inoculated leaves of
      transgenic-resistant tobacco plants. The inhibition of long-distance movement was
      a consequence of restricted entry of the infectious entity into the vascular
      system.

PMID- 9168888
TI  - HTLV-I infection in squirrel monkeys (Saimiri sciureus) using autologous,
      homologous, or heterologous HTLV-I-transformed cell lines.
AB  - Peripheral blood mononuclear cells (PBMC) from three adult male squirrel monkeys
      (Saimiri sciureus) were transformed by human T-cell leukemia/lymphoma virus type
      I (HTLV-I) by cocultivation with lethally irradiated human MT-2 cells. Three
      permanent monkey T-cell lines producing HTLV-I were obtained and characterized.
      Six weeks after inoculation seroconversion was observed in three of three monkeys
      inoculated with autologous transformed T cells and in two of three monkeys
      receiving homologous cells. Proviral DNA was detected in their PBMC at various
      times after inoculation, with the highest proviral load and antibody titers being
      found in monkeys infected with homologous cells. Monkeys inoculated with
      heterologous MT-2 cells did not seroconvert, and HTLV-I provirus was detected
      only transiently in their PBMC. To determine whether in vitro and in vivo HTLV-I
      infection of squirrel monkey cells led to a selection of monkey-adapted viral
      mutants, comparative sequencing of the proviral gp21 env between ex vivo monkey
      HTLV-I-infected PBMC, the inoculum, and MT-2 cells was done and no significant
      differences were detected. The squirrel monkey, which is naturally free of simian
      T-cell leukemia/ lymphoma virus, thus appears to be a suitable model for
      evaluating HTLV-I candidate vaccines and for studying the pathogenesis of HTLV-I.

PMID- 9168889
TI  - The NS2 polypeptide of parvovirus MVM is required for capsid assembly in murine
      cells.
AB  - Mutants of minute virus of mice (MVM) which express truncated forms of the NS2
      polypeptide are known to exhibit a host range defect, replicating productively in
      transformed human cells but not in cells from their normal murine host. To
      explore this deficiency we generated viruses with translation termination codons
      at various positions in the second exon of NS2. In human cells these mutants were
      viable, but showed a late defect in progeny virion release which put them at a
      selective disadvantage compared to the wildtype. In murine cells, however, duplex
      viral DNA amplification was reduced to 5% of wildtype levels and single-strand
      DNA synthesis was undetectable. These deficiencies could not be attributed to a
      failure to initiate infection or to a generalized defect in viral gene
      expression, since the viral replicator protein NS1 was expressed to normal or
      elevated levels early in infection. In contrast, truncated NS2 gene products
      failed to accumulate, so that each mutant exhibited a similar NS2-null phenotype.
      Expression of the capsid polypeptides VP1 and VP2 and their subsequent assembly
      into intact particles were examined in detail. Synchronized infected cell
      populations labeled under pulse-chase conditions were analyzed by differential
      immunoprecipitation of native or denatured extracts using antibodies which
      discriminated between intact particles and isolated polypeptide chains. These
      analyses showed that at early times in infection, capsid protein synthesis and
      stability were normal, but particle assembly was impaired. Unassembled VP
      proteins were retained in the cell for several hours, but as the unprocessed
      material accumulated, capsid protein synthesis progressively diminished, so that
      at later times relatively few VP molecules were synthesized. Thus in NS2-null
      infections of mouse cells there is a major primary defect in the folding or
      assembly processes required for effective capsid production.

PMID- 9168890
TI  - Adaptation of measles virus to polarized epithelial cells: alterations in virus
      entry and release.
AB  - We have previously shown that the Edmonston strain of measles virus enters and is
      released preferentially at the apical surfaces of polarized epithelial cells.
      Small amounts of virus were found to be released at the basal surface. In the
      present study, we passaged the virus in polarized cells and characterized the
      passaged virus for its pattern of entry and release in epithelial cells as well
      as the ability to downregulate the receptor CD46. In contrast to the original
      stock virus, the passaged virus was found to be released at close to the same
      levels from both the apical and the basal surfaces. Accumulation of viral
      nucleocapsids and virus budding were observed at both membrane surfaces when
      cells were infected with the passaged virus. The passaged virus was also found to
      enter efficiently at the basal surface, unlike the original stock virus.
      Syncytial formation was observed at earlier times postinfection in cells infected
      with the passaged virus compared to cells infected with the stock virus. On Caco
      2 cells, CD46 is found on both surfaces but is preferentially expressed on the
      apical membrane. The original Edmonston stock and two other wild-type strains,
      Chicago and Davis, were found to downregulate CD46 levels on the apical but not
      on the basolateral membrane of Caco-2 cells, while the passaged Edmonston measles
      virus did not downregulate CD46 on either surface. These data indicate that
      passage of measles virus through polarized epithelial cells results in selection
      of virus which exhibits a bidirectional pattern of entry and release through both
      the apical and the basolateral surface and which no longer downregulates CD46
      expression on the cell surface.

PMID- 9168891
TI  - Differential immune recognition of LCMV nucleoprotein and glycoprotein in
      transgenic mice expressing LCMV cDNA genes.
AB  - We have generated doubly transgenic (DT) mice that independently express cDNA
      genes for the nucleocapsid protein (NP) and the surface glycoproteins (GP) of
      lymphocytic choriomeningitis virus (LCMV). By RT-PCR, transcription of both
      transgenes was detected at low levels in brain and kidney but was not observed in
      the thymus. Additionally, transcription of the GP transgene was observed in the
      spleen. Following challenge with exogenous LCMV, an anti-NP CTL response was
      induced in LCMV-infected DT mice, suggesting that nonresponsiveness to NP had not
      been established. In contrast, LCMV- infected DT mice were nonresponsive to GP
      and failed to mount any CTL response against GP, either at Day 7 or Day 30
      postinfection or following expansion of splenocyte populations in vitro. A
      significant number (33%) of adult DT mice survived intracerebral infection with
      LCMV, suggesting that virus-induced immunopathology in the central nervous system
      can be diminished by combined expression of the transgenes whereas no protective
      effect was conferred on singly transgenic mice, expressing NP or GP alone. The DT
      mice therefore create a novel host genetic background for comparative studies of
      the anti-LCMV immune responses relative to parental C57Bl/6 mice.

PMID- 9168892
TI  - AP-1 cis-response elements are involved in basal expression and Vmw110
      transactivation of the large subunit of herpes simplex virus type 2
      ribonucleotide reductase (ICP10).
AB  - The promoter of the large subunit of herpes simplex virus type 2 ribonucleotide
      reductase (ICP10) has two AP-1 cis-response elements, respectively located at
      positions -62 and -94 relative to the transcription start site (Wymer et al.,
      1989. J. Virol. 63, 2773-2784). Chloramphenicol acetyl transferase (CAT) analysis
      with hybrid constructions of the CAT structural gene and the ICP10 promoter or
      its mutants and gel retardation studies were used to examine the role of the AP-1
      cis-response elements in expression from the ICP10 promoter. Basal expression
      from the wild-type promoter was significantly (75-90%) reduced by mutation of the
      upstream or downstream AP-1 element. Mutation in the upstream AP-1 element also
      caused a 60% reduction in c-Jun-mediated activation. Activation was decreased 40%
      by mutation in the downstream AP-1 element and it was abrogated by mutation of
      both elements. Similar results were obtained for ACT-deleted mutants and mutants
      in which CT was mutated to AG. The trans-activation by Vmw110 was also reduced by
      mutation of the AP-1 elements (10- and 2-fold for the upstream and downstream
      element, respectively) and it was abrogated by mutation of both AP-1 elements.
      Mutation of nucleotides adjacent to the AP-1 cis-response elements had no effect
      on trans-activation. Gel retardation assays with a DNA probe representing the
      wild-type ICP10 promoter and nuclear extracts from HSV-1-infected cells
      identified one complex that was not seen with mock-infected cells or with cells
      infected with a Vmw110-deleted mutant. The complex was not seen when HSV-1
      infected cells were reacted with an AP-1-mutant DNA probe, and its formation was
      competed by an AP-1 but not a mutant AP-1 oligonucleotide. The migration of this
      complex was retarded by c-Fos antibody, suggesting that both AP-1 and Vmw110 are
      involved in its formation. A mutant deleted in all sequences upstream of the TATA
      box was also activated by Vmw110, but this activation was only 2-fold lower than
      that seen for the wild type and significantly higher (10-fold) than that seen for
      the double AP-1 mutants. The data suggest that AP-1 elements play a crucial role
      in ICP10 gene expression/activation.

PMID- 9168893
TI  - A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig
      tailed macaques has a limited number of amino acid substitutions in both SIVmac
      and HIV-1 regions of the genome and has offered cytotropism.
AB  - We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat,
      rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of
      chimeric simian-human immunodeficiency virus (SHIV) isolated from the
      cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus
      (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence
      analysis of PCR-amplified products revealed a total of 5 nucleotide changes in
      the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had
      no consensus amino acid substitutions, whereas vpr had 1 consensus substitution.
      The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino
      acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which
      originally had an ACG at the beginning of the gene, reverted to an initiation ATG
      codon and in addition contained a consensus amino acid substitution at position
      69 of this protein. As expected, the majority of the nucleotide substitutions
      were found in the env and nef genes. Thirteen and 5 amino acid changes were
      predicted for the corresponding Env and Nef proteins, respectively. In addition,
      one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino
      acid deletion in the V4 region. Using three independent assays, we determined
      that the changes in the SHIVKU-1 were associated with an increase in the
      efficiency of replication in macrophages. The strikingly few consensus changes in
      the virus suggest that conversion of this virus to one capable of causing AIDS in
      pig-tailed macaques was associated with relatively few changes in the viral
      envelope and/or accessory genes. These results will provide the basis for the
      development of a pathogenic, molecular clone of SHIV capable of causing AIDS in
      pig-tailed macaques.

PMID- 9168894
TI  - Daidzein sulfoconjugates are potent inhibitors of sterol sulfatase (EC 3.1.6.2).
AB  - Recent studies have associated high dietary isoflavone intake with low incidence
      of breast cancer. Since estrogenic steroids are important factors in the
      evolution of breast cancer, and in breast tumors they are derived mainly from the
      sterol sulfatase pathway, we have therefore investigated effects of the
      isoflavone daidzein and its sulfoconjugates, daidzein-4'-O-sulfate and daidzein
      7,4'-di-O-sulfate, on sterol sulfatase acitivity using dehydroepiandrosterone
      sulfate as substrate. While daidzein does not affect sterol sulfatase, its
      sulfoconjugates are potent inhibitors of this enzyme. Kinetic analyses reveal
      that daidzein-4'-O-sulfate and daidzein-7,4'-di-O-sulfate inhibit sterol
      sulfatase competitively with respect to the steroid substrate and with Ki values
      of 5.9 and 1 microM, respectively. Daidzein sulfo-conjugates also inhibit
      hydroxysteroid and phenol sulfotransferases but at much higher concentrations.
      These results provide a biochemical basis for the putative chemopreventive role
      of dietary isoflavones against breast cancer.

PMID- 9168895
TI  - Identification of a novel allele at the human NAT1 acetyltransferase locus.
AB  - Humans possess two N-acetyltransferase isozymes (NAT1 and NAT2). We cloned and
      sequenced a novel NAT1 allele (Genbank HSU 80835) that contained nucleotide
      substitutions at -344 (C-->T), -40 (A-->T), 445 [G-->A(Val-->Ile)], 459 [G-
      >A(silent)], 640 [T-->G(Ser-->Ala)], a 9 base pair deletion between nucleotides
      1065 and 1090, and 1095 (C-->A). The novel NAT1 allele which we have designated
      NAT1*17 is similar to NAT1*11 except for a G445A substitution (Val149-->Ile) in
      the NAT1 coding region. The G445A (Val149-->Ile) substitution yielded no
      significant changes in levels of immunoreactivity, as detected by Western blot,
      nor in intrinsic stability of the recombinant N-acetyltransferase protein.
      However, the G445A (Val149-->Ile) substitution yielded expression of recombinant
      NAT1 protein that catalyzed the N-acetylation of aromatic amines and the O- and
      N,O-acetylation of their N-hydroxylated metabolites at rates up to 2-fold higher
      than wild-type recombinant human NAT1.

PMID- 9168896
TI  - Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members
      of the TNF receptor superfamily.
AB  - CD30 is present on the surfaces of malignant cells from patients with Hodgkin's
      lymphoma, anaplastic large cell lymphoma, and other lymphomas. The yeast two
      hybrid genetic screen method was used to identify molecular effectors which
      mediate CD30 signalling events. Clones corresponding to genes coding for TRAF1,
      TRAF2, and TRAF3 molecules, postulated to be involved in signalling via the TNF
      and CD40 receptors, were isolated. In this report, we show that the CD30
      intracellular tail contains two motifs that bind TRAFs. The more amino terminal
      motif, 558PHYPEQET565, binds TRAF2 and 3, while the more carboxyl terminal motif,
      576MLSVEEEG583, binds TRAF1 and 2. We show that these amino acid motifs are
      conserved in TNFRp75 and CD40 and that sequences in these receptors homologous to
      TRAF-binding sequences found in CD30 can selectively bind the TRAFs in a
      predictable manner.

PMID- 9168897
TI  - Immunodetection of a protein related to mammalian arrestin in Euglena gracilis.
AB  - Six monoclonal antibodies directed against different epitopes of bovine retinal
      arrestin recognized a single polypeptide in extracts of achlorophyllous Euglena
      gracilis cells. This polypeptide had an apparent molecular weight slightly lower:
      45kDa vs. 48 kDa, and a more basic isoelectric point compared to that of bovine
      visual arrestin. It was located in an insoluble cytoplasmic fraction.
      Immunofluorescence assays show a cytoplasmic punctuated pattern suggesting a
      cluster distribution or a linkage to some cell structure. The presence of
      arrestine-like molecules in achlorophyllous Euglena gracilis cells suggests that
      these proteins might be involved in a peculiar step of chemical signal
      transduction processes.

PMID- 9168898
TI  - Restoration of fast inactivation in an inactivation-defective human heart sodium
      channel by the cysteine modifying reagent benzyl-MTS: analysis of IFM-ICM
      mutation.
AB  - It has been suggested that the region linking domain III and IV of voltage-gated
      sodium channels forms the inactivation gate. A combination of site-directed
      mutagenesis, cysteine covalent modification, and electrophysiological recording
      techniques was used to identify the role of the Phe1486, a conserved
      phenylalanine residue located in the III-IV linker of Na+ channels. This Phe1486
      is part of a hydrophobic amino acid cluster (IFM) that was proposed to play an
      essential role in the fast inactivation of voltage-gated sodium channels.
      Expression in tsA201 cells of an altered human heart 1 Na+ channel (hH1/F1486C)
      in which Phe1486 was replaced by a cysteine is associated with the appearance of
      a residual current, a loss of voltage-dependence of the time constants of
      inactivation, a shift of the steady-state inactivation to more depolarized
      voltages, and a recovery from inactivation that is faster than the wild-type hH1.
      Exposure of the cytoplasmic surface of mutant F1486C to the methanthiosulfonate
      reagents, MTSEA, MTSET, and MTSES, further disrupted macroscopic inactivation,
      but exposure to MTSBN completely restores fast inactivation and the voltage
      dependence of fast inactivation. These findings support the formulation that the
      IFM motif of the III-IV-linker of voltage-gated sodium channels serves as an
      essential component of the inactivation particle and that the phenyl group of
      Phe1486 may play a crucial role in inactivation gate closure.

PMID- 9168899
TI  - The role of mex-gene products in antibiotic extrusion in Pseudomonas aeruginosa.
AB  - The antibiotic extrusion machinery in Pseudomonas aeruginosa is assembled from
      the mex-operon encoded proteins, OprM and MexA-MexB, connecting the outer and
      inner membranes. To envisage the role of these proteins in antibiotic extrusion
      and resistance, we employed the gene replacement technique to construct mutants
      deficient in mexA, mexB, or oprM, and all possible combinations of these genes.
      Using the Southern and the Western blotting methods, we confirmed that only the
      target genes were disrupted. All the mutants deficient in OprM exhibited a 4 to
      16 times higher susceptibility against quinolone antibiotics, chloramphenicol,
      and gentamicin than the parent strain. The mutants deficient in MexA or MexB or
      both MexA and MexB were only 2 to 4 times more susceptible to these antibiotics
      than the parent strain. All the mutants lacking MexA, MexB, or OprM showed
      stereospecific hypersusceptibility to beta-lactam antibiotics than the parent
      strain. However, the extent of susceptibility to each beta-lactam was comparable
      among the mutants. Strains lacking OprM accumulated the highest level of
      ciprofloxacin among all these isogenic strains. The strains lacking either MexA
      or MexB accumulated lower levels of ciprofloxacin than the mutant lacking OprM,
      but the levels were still higher than in the parent strain. The results are
      consistent with the antibiotic susceptibility of these strains. These results
      suggest that the extrusion of antibiotics occurs most efficiently with a whole
      assembly of MexA/B-OprM, but it remains a possibility that OprM interacts with a
      putative inner membrane pump(s).

PMID- 9168900
TI  - Murine Cyp1a-1 induction in mouse hepatoma Hepa-1C1C7 cells by myristicin.
AB  - Mouse hepatoma Hepa-1c1c7 (Hepa-1) cells were treated with myristicin to assess
      the role of myristicin in the process of Cyp1a-1 induction. Treatment of Hepa-1
      cells with myristicin increased Cyp1a-1 transcription in a dose-dependent manner
      as shown by analysis of 7-ethoxyresorufin O-deethylase activity, Cyp1a-1 protein
      level, and Cyp1a-1 mRNA. Myristicin, however, did not competitively displace
      [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin from the Hepa-1 cytosolic aryl
      hydrocarbon (Ah) receptor in a competitive Ah receptor binding analysis using
      sucrose density gradient sedimentation and did not affect formation of DNA
      protein complexes between the Ah receptor and its DRE target in a gel mobility
      shift assay using oligonucleotides corresponding to DRE 3 of the Cyp1a-1. These
      results suggest that the induction of Cyp1a-1 gene expression by myristicin in
      Hepa-1 cells might occur through an Ah receptor-independent pathway.

PMID- 9168901
TI  - Induction of CYP1A1 by beta-naphthoflavone in IEC-18 rat intestinal epithelial
      cells and potentiation of induction by dibutyryl cAMP.
AB  - We have examined the inducibility of CYP1A1 by beta-naphthoflavone (BNF) in a rat
      intestinal epithelial cell line, IEC-18, and the associated interaction between
      cAMP and BNF. CYP1A1 was not constitutively expressed in IEC-18 cells. Upon
      treatment with BNF, CYP1A1 RNA, protein, and microsomal 7-ethoxyresorufin O
      deethylase activity were detected. Treatment with dibutyryl cAMP resulted in a 2
      fold increase in the extent of induction at both RNA and protein levels, with
      corresponding increases in CYP1A1 enzymatic activity. These results support the
      involvement of protein kinase A in Ah receptor-mediated induction of CYP1A1 and
      provide an in vitro model for further studies on the mechanisms underlying
      regional and cellular differences in the regulation of CYP1A1 gene expression in
      the small intestine.

PMID- 9168902
TI  - DnaJ potentiates the interaction between DnaK and alpha-helical peptides.
AB  - Molecular chaperones bind selectively to nascent, unfolded, misfolded, or
      aggregated polypeptides, and are involved in protein folding, protein targeting
      to membranes, and protein renaturation after stress. The DnaK chaperone of
      Escherichia coli is known to interact preferentially with positively charged
      hydrophobic peptides in an extended conformation. Accordingly, we show in the
      present study that DnaK has a low affinity for alpha-helical peptides. In the
      presence of its co-chaperone DnaJ and ATP, however, DnaK interacts more
      efficiently with alpha-helical peptides. This suggests that DnaJ triggers a
      conformational change in DnaK which improves its interaction with these peptides.
      The ability of the DnaK/DnaJ/GrpE chaperone machine to interact with alpha
      helical peptides (which represent the most frequent secondary structure in
      proteins) should be an important part of its role in protein folding and
      renaturation.

PMID- 9168903
TI  - Extrahepatic expression of NAD(P)H:menadione oxidoreductase, UDP
      glucuronosyltransferase-1A6, microsomal aldehyde dehydrogenase, and hepatic
      nuclear factor-1 alpha mRNAs in ch/ch and 14CoS/14CoS mice.
AB  - Oxidative stress-induced gene expression in liver of the untreated newborn
      c14CoS/c14CoS mouse, as compared with that in the cch/cch wild-type mouse,
      appears to be caused by homozygous loss of the fumarylacetoacetate hydrolase
      (Fah) gene on Chr 7 and absence of the FAH enzyme, which leads to increased
      levels of endogenous reactive oxygenated metabolites (ROMs) formed in the
      tyrosine degradative pathway. In these mice almost all studies to date have been
      carried out in liver. We have examined the extrahepatic expression of four genes.
      Two genes are members of the [Ah] battery and induced by ROM-mediated oxidative
      stress: NAD(P)H:menadione oxidoreductase (Nmo1) and UDP glucuronosyltransferase
      1A6 (Ugt1a6). The other two genes are decreased in the livers of 14CoS/ 14CoS
      mice as compared with that in ch/ch mice: microsomal aldehyde dehydrogenase
      (Ahd3) and hepatocyte-specific nuclear factor-1 alpha HNF-1 alpha (Hnf1 alpha).
      In liver plus nine extrahepatic tissues of untreated newborn 14CoS/14CoS mutant
      and ch/ch wild-type mice, we compared NMO1, UGT1A6, AHD3 and HNF-1 alpha mRNA
      levels. Our results show a wide variation in extrahepatic tissue-specific
      expression of all four transcripts and indicate that numerous differences exist
      in the extrahepatic expression of these genes between 14CoS/14CoS and ch/ch mice.

PMID- 9168904
TI  - Mitochondrial encephalomyopathy associated with a novel mutation in the
      mitochondrial tRNA(leu)(UUR) gene (A3243T).
AB  - We report a new mutation, an A-->T transition at nt 3243 in the mitochondrial
      tRNA(leu)(UUR) gene, in a 9-year-old girl who presented with muscle weakness of 3
      years duration complicated by rapidly progressive encephalopathy. In muscle, the
      activity of the mitochondrial respiratory chain complexes I, III, and IV was
      markedly reduced. The mutation, involving a highly conserved base pair in the
      dihydrouridine loop, was heteroplasmic in muscle (81.4%), skin (69.3%), and blood
      (13.8%) and was not present in blood of 50 healthy individuals. The mitochondrial
      3243 base is a "hot spot" for mutations; an A-->G transition at this position is
      found in a high proportion in most MELAS patients. Since the A-->T transition
      creates a new recognition site for the restriction enzyme TspRI, both ApaI and
      TspRI should be used to exclude a mutation at nt 3243.

PMID- 9168905
TI  - Solution conformation of nociceptin.
AB  - Nociceptin, a novel heptadecapeptide, interacts with ORL1 a G protein-coupled
      receptor whose sequence is closely related to that of the kappa opioid receptor
      but has no opioid activity. We have investigated the conformational preferences
      of Nociceptin also in comparison to Dynorphin A. The N-terminal part of
      Nociceptin has the same conformational preferences of the message of endogenous
      opioids but the C-terminal part of the sequence is more flexible than the
      corresponding address of Dynorphin A. [Tyr1]-Nociceptin, while retaining
      nociceptive activity, has also an opioid activity comparable to that of
      enkephalins.

PMID- 9168906
TI  - Phosphocholine-containing glycoglycerolipids (GGPL-I and GGPL-III) are species
      specific major immunodeterminants of Mycoplasma fermentans.
AB  - Mycoplasma fermentans has unique glycoglycerophospholipids (GGPLs: GGPL-I and
      GGPL-III). Previously, the structure of these lipids was determined as
      phosphocholine-6'-alpha-glucopyranosyl-(1'-3)-1, 2-diacyl-glycerol (GGPL-I) and
      1"-phosphocholine-2"-aminodihydroxypropane-3"-phospho-6'-alph++ + a-
      glucopyranosyl-(1'-3)-1, 2-diacyl-glycerol (GGPL-III). Thin-layer chromatography
      (TLC) immunostaining showed that the GGPLs were main lipid-antigens of the M.
      fermentans species. Anti-M. fermentans serum stained mainly the GGPLs, but the
      other anti-mycoplasma sera (anti-M. arginini, anti-M. hyorhinis, anti-M.
      pneumonia, anti-M. primatum, and anti-Acholeplasma laidlawii, anti-M. hominis,
      anti-M. orale, and M. salivarium) stained neither GGPL-I nor GGPL-III. The TLC
      analysis of glycolipids and phospholipids of various human related mycoplasmas
      showed clearly that GGPLs are specifically expressed in M. fermentans species.
      GGPL-I and GGPL-III ranged from 1.6 to 28% and from an undetectable level to 35%
      of total phospholipids, respectively. Although there was heterogeneity among the
      amounts of GGPL-I or GGPL-III of M. fermentans strains, all of the M. fermentans
      strains had GGPL-I and/or GGPL-III. These observations showed that GGPL
      structures are species-specific immunodeterminants of M. fermentans. The fact
      that the GGPLs are main phospholipid components of the M. fermentans species
      means the M. fermentans has a unique choline metabolic pathway. This observation
      may raise phylogenetic interest.

PMID- 9168907
TI  - Alternative usage of exon 1 of bovine PrP mRNA.
AB  - Here we report two types of bovine prion protein (PrP) mRNA that possessed
      different lengths of the 5'-untranslated region and were expressed in various
      bovine tissues. The two mRNA species were transcribed from identical positions
      but differed in the usage of the splice site for exon 1/intron. One mRNA
      possessed exon 1 consisting of 53 nucleotides and the other possessed exon 1
      consisting of 168 nucleotides. Usage of exons 2 and 3 was identical for the two
      mRNA species. The two mRNA species were detected in all but spleen tissue; the
      mRNA possessing 168-nt exon 1 was not detected in bovine spleen. This is the
      first report on the tissue-specific alternative splicing of PrPc mRNA in any
      other species. Only a low level of PrPc appeared to be present in bovine spleen.
      These results suggested the possibility that the mRNA possessing 53-nt exon 1 was
      inefficiently translated into Prp; however, in vitro translation analysis showed
      no marked difference in translational efficiency between the two mRNA species.

PMID- 9168908
TI  - Suppression of neutral cholesterol ester hydrolase activity by antisense DNA of
      hormone-sensitive lipase.
AB  - In order to investigate the role of the hormone-sensitive lipase (HSL) gene in
      the activity of neutral cholesterol ester hydrolase (NCEH) from a molecular
      perspective, Chinese hamster ovary (CHO) cells were transfected with rat
      antisense hormone-sensitive lipase cDNA, and three different cell lines,
      designated as anti-HSL, were established. NCEH activity in anti-HSL cells was
      reduced to approximately 50% of that in control CHO cells. The concentration of
      cellular esterified cholesterol increased and the concentration of free
      cholesterol decreased in the anti-HSL cell lines. These results suggest that the
      HSL gene has a function of NCEH as well.

PMID- 9168909
TI  - Hypocholesterolemic effect of lycopene and beta-carotene is related to
      suppression of cholesterol synthesis and augmentation of LDL receptor activity in
      macrophages.
AB  - Beta-Carotene and lycopene are derived from plants, and they share similar
      initial synthetic pathway with cholesterol, which is synthesized in animal but
      not in plant cells. Thus, we sought to analyze the effect of carotenoids on
      macrophage cholesterol metabolism, in comparison to the effect of LDL cholesterol
      and of the cholesterol synthesis inhibitor, fluvastatin. In J-774 A. 1 macrophage
      cell line, the cellular cholesterol synthesis from [3H]-acetate, but not from
      [14C] mevalonate, was suppressed by 63% any by 73% following cell incubation with
      beta-carotene or lycopene (10 microM) respectively, in comparison to a 90% and
      91% inhibition by LDL (100 micrograms of cholesterol), or by fluvastatin (10
      micrograms/ml) respectively. However, unlike LDL derived cholesterol, which also
      suppresses macrophage LDL receptor activity, lycopene and beta-carotene augmented
      the activity of the macrophage LDL receptor, similarly to the effect of
      fluvasfatin. In agreement with these in vitro observations, dietary
      supplementation of tomato's lycopene (60 mg/day) to 6 males for a 3 months period
      resulted in a significant 14% reduction in their plasma LDL cholesterol
      concentrations. We thus conclude that dietary supplementation of carotenoids may
      act as moderate hypocholesterolemic agents, secondary to their inhibitory effect
      on macrophage 3-hydroxy-3-methyl glutaryl coenzyme A (HMGCoA) reductase, the rate
      limiting enzyme in cholesterol synthesis.

PMID- 9168910
TI  - Transient expression of multiple genes in salinity-stressed young seedlings of
      rice (Oryza sativa L.) cv. bura rata.
AB  - To date only about 15 abundantly expressed osmoresponsive genes/proteins have
      been described in rice cultivars. Using in vivo radiolabeling followed by two
      dimensional electrophoresis and autoradiography, a record number of at least 35
      salinity stress-induced polypeptides (14-90 kDa) and 17 salt stress-repressed
      polypeptides were detected in a halotolerant Indica rice cultivar Bura Rata.
      These include > 20 hitherto unreported rice polypeptides that exhibited a low
      abundance, short-term expression during NaCl stress. Prolonged exposure to NaCl
      decreased their synthesis. These findings have widened the scope of further
      investigations into new osmoresponsive genes, especially those with possibly
      transient regulatory functions in rice halotolerance.

PMID- 9168912
TI  - Down-regulation of protein kinase CKII activity by sodium butyrate.
AB  - Butyrate, a dietary fiber derivative, is a well-known differentiating agent in
      cultured cell lines. In addition, its antineoplastic activity toward colon-rectum
      cancers has been documented both in vivo and in vitro. Despite the large amount
      of information on the potential clinical efficacy of butyrate, its mechanism of
      action at the molecular level has only been partially investigated. Here, we show
      that serine/threonine protein kinase CKII is a target of butyrate activity. In
      the human adenocarcinoma cell line, HT29, treated with 2 mM sodium butyrate, CKII
      activity decreases 50% at 24 and 48 hours after drug addition. The enzyme down
      regulation is not due to changes in protein amount since the levels of the
      different CKII subunits remain constant during butyrate treatment. The data
      reported provide the first evidence that CKII down-regulation is involved in the
      signal transduction pathway started by butyrate.

PMID- 9168911
TI  - Release of isoprostanes by human pulmonary artery in organ culture: a cyclo
      oxygenase and nitric oxide dependent pathway.
AB  - Isoprostanes are prostaglandin (PG)-like compounds initially described as formed
      by a direct action of radicals on arachidonic acid. However, the isoprostane 8
      iso PGF2 alpha, is released by platelets and monocytes by cyclo-oxygenase
      dependent pathways. The free radical NO can modulate arachidonic acid metabolism
      in some cells, but its potential role in isoprostane formation has not been
      studied. Using human pulmonary artery in organ culture (24 h), we therefore
      investigated the role of cyclo-oxygenase and NO in 8-iso PGF2 alpha release. In
      endothelium-denuded segments of pulmonary artery, the inflammatory agennts tumor
      necrosis factor alpha, interleukin-1 beta, interferon gamma, and
      lipopolysaccharide stimulated the release of PGE2 and 8-iso PGF2 alpha, which
      were attenuated in both cases by the cyclo-oxygenase inhibitor indomethacin. By
      contrast, the NO synthase inhibitor L-N(G)-intro-L-arginine methyl ester
      inhibited 8-iso PGF2 alpha but not PGF2 release. Thus, we show for the first time
      that human pulmonary vessels can produce isporostanes and that NO synthase and
      cyclo-oxygenase pathways are involved in their release.

PMID- 9168914
TI  - The stereospecificity of hydrogen transfer to NAD(P)+ catalyzed by lactol
      dehydrogenases.
AB  - The stereochemistry of hydrogen transfer to NAD(P)+ has been determined for five
      lactol dehydrogenases. It was found that D-glucose dehydrogenases from Bacillus
      megaterium and Cryptococcus uniguttulatus and L-rhamnose dehydrogenase from
      Aureobasidium pullulans are pro-S (B) specific, while D-glucose dehydrogenase
      from Thermoplasma acidophilum and D-xylose dehydrogenase from procine liver are
      pro-R (A) specific. The latter two enzymes are the first examples of A-specific
      dehydrogenases oxidizing aldoses at the anomeric carbon. These findings are
      discussed in terms of functional and historical models that seek to make
      predictive generalizations regarding dehydrogenase stereospecificity.

PMID- 9168913
TI  - Interferon regulates expression of mda-6/WAF1/CIP1 and cyclin-dependent kinases
      independently from p53 in B16 murine melanoma cells.
AB  - Interferons (IFNs) induce growth arrest and terminal differentiation through
      regulation of proliferative genes in a variety of cell types including tumor
      cells. Growth of melanoma cells is believed to be controlled by the cyclin
      dependent kinase inhibitor, mda-6/WAF1/CIP1 gene. IFNs affect the expression of
      WAF1 in several cell types, including human melanomas. In our earlier reports we
      demonstrated the antitumor and anticellular activities of different IFN-types on
      B16 murine melanoma cells. The present study aimed to demonstrate the involvement
      of mda-6/WAF1 and related cyclin-dependent kinases in antitumor action of
      different IFN-types in B16 melanoma cells. IFN-alpha has been proven to be a
      potent inducer of mda-6/WAF1, also inhibiting cyclin-dependent kinases, such as
      cdc2- and cdk2-kinase. This induction is p53-independent. However, IFN-gamma
      affects B16 cells differently, it induces p53 activity without inducing WAF1. The
      combination of IFN-alpha plus IFN-gamma is additive rather than synergistic. Our
      data demonstrate differential effects of different IFNs on murine B16 melanoma
      cells which may have relevance in nonsurgical treatment of melanomas.

PMID- 9168915
TI  - Formation of a molten-globule-like state of myoglobin in aqueous
      hexafluoroisopropanol.
AB  - The effects of aqueous hexafluoroisopropanol (HFIP) media on the structure of
      myoglobin are reported. Circular dichroism (CD) spectra of this alpha-helical
      protein in as little as 4% (v/v) HFIP indicate that native-like amounts of
      secondary structure remain while rigid tertiary structure is lost. However,
      thermal studies suggest some residual cooperativity of unfolding in this state.
      At much higher HFIP concentrations, the helicity exceeds the native value and the
      protein behaves as a series of independent helices which do not interact with
      each other. We did not observe cold denaturation of myoglobin, even though this
      phenomenon has been observed for molten globule states of myoglobin, as well as
      for monomeric amphipathic alpha-helices when moderate quantities of HFIP are
      present. The pH dependence of trifluoroethanol-induced disruption of tertiary
      structure revealed that the degree of disruption increases as the enthalpic
      advantage of the folded state is diminished at low pH.

PMID- 9168916
TI  - Curcumin and genistein, plant natural products, show synergistic inhibitory
      effects on the growth of human breast cancer MCF-7 cells induced by estrogenic
      pesticides.
AB  - Curcumin and genistein are two natural products of plants obtained from Curcuma
      longa Linn (turmeric) and soybeans, respectively. Both compounds when present at
      micromolar concentrations are able to inhibit the growth of estrogen-positive
      human breast MCF-7 cells induced individually or by a mixture of the pesticides
      endosulfane, DDT and chlordane or 17-beta estradiol. When curcumin and genistein
      were added together to MCF-7 cells, a synergistic effect resulting in a total
      inhibition of the induction of MCF-7 cells by the highly estrogenic activity of
      endosulfane/chlordane/DDT mixtures was noted. These data suggest that the
      combination of curcumin and genistein in the diet have the potential to reduce
      the proliferation of estrogen-positive cells by mixtures of pesticides or 17-beta
      estradiol. Since it is difficult to remove pesticides completely from the
      environment or the diet and since both turmeric and soybeans are not toxic to
      humans, their inclusion in the diet in order to prevent hormone related cancers
      deserves consideration.

PMID- 9168917
TI  - Inhibition of human leukocyte proteinase 3 by a novel recombinant serine
      proteinase inhibitor (LEX032).
AB  - The interaction of a bioengineered serpin (LEX032) with human leukocyte
      proteinase 3 (PR 3) has been investigated. LEX032 was found to be a time
      dependent inhibitor of PR 3, forming a highly-stable enzyme-inhibitor complex (Ki
      12 nM).

PMID- 9168918
TI  - The expression of genes modulating programmed cell death in normal human
      polymorphonuclear neutrophils.
AB  - Normal human polymorphonuclear neutrophils (PMN) have a short life and die in
      progression via apoptosis. In order to understand the molecular basis of PMN
      apoptosis, the expression of apoptosis-related (Fas, Fas-ligand, p53, and c-myc)
      and survival-related (bcl-2) genes was detected by flow cytometry, Western blot
      and reverse transcription-assisted polymerase chain reaction (RT-PCR). We found
      that Fas and Fas-ligand (FasL) were expressed on the surface of most of the
      cells. However, the disappearance of FasL was much faster than Fas after 24 h
      incubation. p53 and bcl-2 were also expressed in the cytoplasm of most of the
      cells. In contrast, the expression of c-myc was negligible in PMN. The addition
      of monoclonal anti-human Fas antibody (25 micrograms/ml) to PMN suspension
      enhanced whereas anti-FasL antibody (25 micrograms/ml) suppressed PMN apoptosis
      in 48 h incubation. These results suggest that the activation of Fas pathway
      induced by Fas-FasL interaction among PMNs is one of the mechanisms for
      spontaneous PMN apoptosis. Lack of proto-oncoprotein c-myc expression in PMN is
      responsible for their non-proliferative property and may aggravate the
      spontaneous apoptosis of the cells.

PMID- 9168919
TI  - Caveolin and MAL, two protein components of internal detergent-insoluble
      membranes, are in distinct lipid microenvironments in MDCK cells.
AB  - The MAL proteolipid and caveolin have been identified as components of internal
      detergent-insoluble membrane microdomains enriched in glycolipids and
      cholesterol. We have addressed the study of the glycolipid-enriched membranes in
      cells expressing endogenously only either MAL (Jurkat T cells) or caveolin
      (epithelial A498 cells) and in polarized MDCK cells which express both proteins
      simultaneously. Subcellular fractionation by centrifugation to equilibrium in
      sucrose gradients of Triton X-100 cell extracts from Jurkat and A498 cells
      revealed that MAL and caveolin are incorporated in detergent-insoluble buoyant
      membranes independently of the expression of each other and indicated the
      existence in these cells of insoluble membrane microdomains with either MAL or
      caveolin. Immunofluorescence analysis in MDCK cells indicated that both MAL and
      caveolin were located in the Golgi region, whereas caveolin was found in addition
      at the cell surface. Biochemical analysis in these cells revealed the existence
      of distinct membrane microenvironments differentially susceptible to detergent
      solubilization containing either internal MAL or internal plus surface caveolin.
      The observed heterogeneity within the internal glycolipid-enriched membrane
      fraction suggests the existence of distinct specialized lipid microenvironments
      in MDCK cells.

PMID- 9168920
TI  - The role of the N-terminal leucine residue in snake venom cardiotoxin II (Naja
      naja atra).
AB  - The N-terminal leucine residue of snake venom cardiotoxin II (CTX II) (Naja naja
      atra) was systematically replaced with D-leucine (CTXII-L1-D-L), glycine (CTXII
      L1G) or deleted [CTXII-(2-60)] to study the role of leucine residue in CTX II
      molecule. CTX II, CTXL1-D-L, CTXL1G and CTX(2-60) were produced by chemical
      synthesis method and purified by high performance liquid chromatography. Owing to
      folding problem in CTXII-(2-60), only CTX II, CTXII-L1-D-L and CTXII-L1G were
      produced in a pure form and characterized by amino acid analysis, mass
      spectrometry and peptide mapping. In the structural aspect, changing the Leu-1 by
      D-Leu or Gly causes a drastic alteration in the whole CTX II structure as
      detected by circular dichroism, 1-anilino-naphthalene-8-sulfonate (ANS)
      fluorescence assay. In the functional aspect, both CTXII-L1-D-L and CTXII-L1G are
      still retained substantial biological activity of CTX II. Therefore, the results
      indicate that both the chirality and the side-chain of the N-terminal leucine
      residue of CTX II are important elements in maintaining the whole CTX II
      structure. In addition, this study is the first report in elucidating the reason
      why the first N-terminal residue of most CTXs (90.3%) is leucine residue.

PMID- 9168921
TI  - Telomerase activity is elevated in early S phase in hamster cells.
AB  - Telomerase is a ribonucleoprotein that elongates telomeric repeats de novo. We
      examined the possibility that telomerase activity is cell cycle regulated by
      examining telomerase activity in cell cycle synchronized Chinese hamster ovary
      (CHO) B11 cells. Overall telomerase activity was similar in growing and quiescent
      cells. Further, cells synchronized in G1, S, or G2/M showed similar levels of
      telomerase activity. However, a detailed analysis of cells within S phase showed
      that there was a higher level of telomerase activity in early S phase when
      compared with other points in the cell cycle. These results suggest a
      relationship between telomerase activity and cell cycle regulation.

PMID- 9168922
TI  - Two N-terminal self-association domains are required for the dominant negative
      transcriptional activity of WT1 Denys-Drash mutant proteins.
AB  - Patients with Denys-Drash syndrome (DDS) have been shown to be constitutionally
      heterozygous for mutations of the WT1 gene. Almost all DDS mutations inactivate
      or remove the DNA-binding zinc finger region of WT1 and the resulting mutant
      proteins appear to act in a dominant negative manner. This may occur via WT1 self
      association, which has been shown to involve the first 180 amino acids. By
      creating a series of N-terminal deletions, we have further investigated WT1 self
      association using a yeast di-hybrid system and an in vitro protein binding assay.
      Our results suggest that there are two distinct domains within the N-terminal
      region facilitating self-association, residing from amino acids 1-45 and 157-253.
      Co-transfection of WT1 with progressively shorter N-terminal constructs
      demonstrates that both of these sites are required for a dominant negative
      activity as assessed by activation of a reporter construct.

PMID- 9168923
TI  - Involvement of the transcriptional factor GATA-1 in regulation of expression of
      coproporphyrinogen oxidase in mouse erythroleukemia cells.
AB  - Coproporphyrinogen oxidase (CPO; EC 1.3.3.3), the sixth enzyme of heme
      biosynthesis, transcribed from a single promoter is markedly induced during
      erythroid differentiation. CPO is ubiquitously expressed in all cells. To
      determine cis-acting elements of the human CPO gene, the promoter region of the
      gene was isolated, and three potential GATA-1 motifs and four GC boxes were found
      within this fragment. In a functional analysis of various deletion mutants, we
      found that the GATA-1 binding site at -143 to -138 was essential for basic and
      inducible expressions of the CPO gene in mouse erythroleukemia (MEL) cells. Gel
      mobility shift assay revealed that GATA-1 bound to the region is required for the
      expression and this was confirmed by observations that the nuclear protein bound
      to the GATA-1 motif was supershifted with anti GATA-1 antibody, by gel mobility
      shift assay. Furthermore, co-expression of mouse GATA-1 in MEL cells led to an
      increase in the promoter activity, which was markedly increased by dimethyl
      sulfoxide-treatment. These results indicate that GATA-1 plays an important role
      in regulation of transcription of the CPO gene in erythroid cells.

PMID- 9168924
TI  - Alternatively spliced isoforms of the Na+/Ca2+ exchanger in the guinea pig
      cochlea.
AB  - The cochlea has been suggested to express some Na+/ Ca2+ exchangers (NCX), since
      efficient acoustic transduction requires cytosolic calcium homeostasis. The
      present study revealed that several spliced isoforms of NCX are expressed in the
      guinea pig cochlea. Moreover, to determine their localization in the cochlea,
      microdissected RT-PCR was performed. The guinea pig cochlea was microdissected
      into three parts (lateral wall, the organ of Corti and modiolus). The cochlear
      lateral wall and the organ of Corti expressed only a single isoform of NCX1. On
      the other hand, five isoforms of NCX1 and four isoforms of NCX3 were detected in
      the cochlear modiolus. The alternative splicing may provide diverse functions for
      NCX in the cochlea.

PMID- 9168926
TI  - Does elevated nitric oxide production enhance the release of prostacyclin from
      shear stressed aortic endothelial cells?
AB  - Nitric oxide (NO) enhances prostacyclin (PGI2) production in agonist-stimulated
      endothelial cells, while peroxynitrite formed from NO and superoxide anion has
      been shown to activate cyclooxygenase. Using cultured bovine aortic endothelial
      cells (BAEC) exposed to arterial levels of laminar shear stress of 25 dynes/ cm2,
      we tested the hypothesis that NO mediated the elevated synthesis of PGI2 by shear
      stressed endothelium. Shear stress caused a large and rapid burst and sustained
      release of NO and PGI2 with the cumulative production at 1 hr enhanced 9.96-fold
      (n = 4, p < 0.005) and 9.16-fold (n = 3, p < 0.005), respectively, over
      stationary control production of 0.0257 nmol-NO/cm2-BAEC and 0.0193 ng-PGI2/cm2
      BAEC. The NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (100 microM,
      LNAME) and N(G)-nitro-L-arginine (10 microM, LNA), caused 87.5 and 65% reductions
      (n = 3, p < 0.02) of cumulative NO release at 1 hr, respectively, and 45 and 55%
      reductions (n = 3, p = 0.025) of PGI2 release, respectively. About half of the
      elevated production of PGI2 in shear stressed cells was due to NO-dependent
      signaling, indicating that hemodynamic control of these two dilatory molecules is
      partially coupled.

PMID- 9168925
TI  - Inhibition of HIV-1 replication by triple-helix-forming phosphorothioate
      oligonucleotides targeted to the polypurine tract.
AB  - We show the effects of triple-helix formation by assays of primer extension
      inhibition in vitro using two systems (two-strand-system (FTFOs) or three-strand
      system (TFOs) targeted to the polypurine tract (PPT) of HIV-1. The FTFOs were
      more effective than the TFOs. We found that the FTFOs containing phosphorothioate
      groups at the 3'- and 5'-ends, or inside the hairpin loop, exhibited higher
      inhibitory effects on cDNA synthesis and greater exonuclease resistance than the
      unmodified FTFOs and TFOs. The abilities of the FTFOs containing phosphorothioate
      groups at the antisense sequence sites to inhibit HIV-1 replications were
      examined. The FTFOs containing phosphorothioate groups at the antisense sequence
      sites inhibit the replication of HIV-1 more efficiently than the antisense
      oligonucleotides, indicating sequence-specific inhibition of HIV-1 replication.

PMID- 9168927
TI  - Palmitoyl-CoA stimulates cellular uptake and plasma membrane binding of
      carnitine.
AB  - Carnitine cellular uptake and plasma membrane binding was investigated in S49
      lymphoma cells. Palmitoyl-CoA was found to increase membrane binding of carnitine
      from 506 +/- 48 to 8,690 +/- 235 pmol/mg membrane protein. Palmitate and CoA
      acted synergistically and increased carnitine binding to plasma membranes but
      could not replace palmitoyl-CoA. The effect of palmitoyl-CoA on membrane binding
      of carnitine was maximal at 10 microM and required the presence of ATP. Palmitoyl
      CoA increased the cellular uptake rate of carnitine from 181 +/- 5 to 884 +/- 25
      amol/cell and h-1. We conclude that palmitoyl-CoA is a major regulator of
      cellular uptake of carnitine and, based on quantitative estimations, that the
      carnitine carrier binds more than one carnitine molecule.

PMID- 9168928
TI  - Chromosomal localization and partial genomic structure of the human peroxisome
      proliferator activated receptor-gamma (hPPAR gamma) gene.
AB  - We determined the chromosomal localization and partial genomic structure of the
      coding region of the human PPAR gamma gene (hPPAR gamma), a nuclear receptor
      important for adipocyte differentiation and function. Sequence analysis and long
      PCR of human genomic DNA with primers that span putative introns revealed that
      intron positions and sizes of hPPAR gamma are similar to those previously
      determined for the mouse PPAR gamma gene[13]. Fluorescent in situ hybridization
      localized hPPAR gamma to chromosome 3, band 3p25. Radiation hybrid mapping with
      two independent primer pairs was consistent with hPPAR gamma being within 1.5 Mb
      of marker D3S1263 on 3p25-p24.2. These sequences of the intron/exon junctions of
      the 6 coding exons shared by hPPAR gamma 1 and hPPAR gamma 2 will facilitate
      screening for possible mutations. Furthermore, D3S1263 is a suitable polymorphic
      marker for linkage analysis to evaluate PPAR gamma's potential contribution to
      genetic susceptibility to obesity, lipoatrophy, insulin resistance, and diabetes.

PMID- 9168929
TI  - Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a
      result of its membrane interactions.
AB  - The biological activity of the Alzheimer's disease amyloid beta protein may be
      related to modulation of membrane lipid peroxidation. The effect of amyloid beta
      protein fragment 25-35 [A beta(25-35)] on lipid peroxidation was examined in
      liposomes enriched with polyunsaturated fatty acids. The activity of A beta(25
      35) was compared to that of A beta(25-35) with either a scrambled sequence [A
      beta(25-35)scram] or a peptide sequence in which methionine was replaced with
      leucine [A beta(25-35) met]. A beta(25-35) inhibited lipid peroxidation in a dose
      and time-dependent manner. The antioxidant activity of A beta(25-35) was
      observed at concentrations as low as 10 nM. The relative antioxidant activities
      of the amyloid beta protein fragments were as follows: A beta(25-35) > A beta(25
      35) met > A beta(25-35)scram. The two more potent peptides intercalated into the
      membrane hydrocarbon core, as determined by small-angle x-ray diffraction
      approaches. These findings indicate that the amphiphilic A beta(25-35) peptide
      inhibits lipid peroxidation at low concentrations as a result of physicochemical
      interactions with the membrane lipid bilayer.

PMID- 9168930
TI  - ERC-55, a binding protein for the papilloma virus E6 oncoprotein, specifically
      interacts with vitamin D receptor among nuclear receptors.
AB  - VDR regulates gene expression in a ligand-dependent way by binding to cognate
      enhancer elements of target gene promoters. The ligand-dependent activation
      function, AF-2, of VDR is thought to require transcriptional co-activators/co
      repressors together with basal transcriptional machinery. Using a yeast two
      hybrid system with VDR, we have isolated a mouse Ca(2+)-binding protein
      (designated as VAF1) specifically interacting in vivo and in vitro with VDR among
      nuclear receptors like RAR, RXR, ER and GR. VAF1 is a mouse homologue to human
      ERC-55, which has recently been shown to interact with human papillomavirus
      oncogenic protein, E6[1]. Unlike those of many previously identified co
      activators, the VDR-VAF1 interaction was ligand-independent. Thus, VAF1 seems a
      putative VDR-specific cofactor modulating its function.

PMID- 9168931
TI  - Molecular cloning and expression analysis of rat Rgs12 and Rgs14.
AB  - We report the cloning of two novel rat regulators of G-protein signaling (RGS)
      cDNAs using a degenerate PCR strategy. The rRgs12 and rRgs14 cDNAs encode
      predicted polypeptides of 1387 and 544 amino acids, respectively. We have also
      identified the human orthologue of rRgs12 by alignment of cosmid sequences in the
      database which map the human RGS12 gene to chromosome 4p16.3. Furthermore, we
      identified human ESTs with high homology to rRgs14 which map to human chromosome
      5qter. Northern blot analysis indicates that rRgs14 is expressed at high levels
      in brain, lung, and spleen, whereas rRgs12 is expressed at high levels in brain
      and lung and lower levels in testis, heart, and spleen. Analysis of the predicted
      rRGS12 and rRGS14 polypeptides indicates that they are closely related and
      possess regions of homology outside of the conserved RGS domain. We have also
      identified conserved regions in RGS12 which are similar to protein domains found
      in mouse rhophilin and coiled-coil proteins suggesting possible interactions with
      ras-like G-proteins.

PMID- 9168932
TI  - Inhibition of lipid peroxidation by N-acetylserotonin and its role in retinal
      physiology.
AB  - N-Acetylserotonin (NAS) inhibits the peroxidation of linoleic acid induced by a
      water-soluble initiator, 2,2'-azobis(2-amidinopropane) (ABAP). Lipid peroxidation
      was detected by the formation of conjugated dienes, monitored
      spectrophotometrically at 236 nm. N-Acetylserotonin, at concentrations ranging
      from 200 nM to 20 microM, reduced the rate of ABAP-initiated lipid peroxidation
      in a concentration-dependent manner. The results of NAS-inhibited lipid
      peroxidation are compared to the antioxidant activities of melatonin, vitamin E,
      and a water-soluble vitamin E analog, Trolox. It is suggested that NAS acts as a
      physiological antioxidant in retinal photoreceptor cells.

PMID- 9168933
TI  - Bcl-2 relieves the trans-repressive function of the glucocorticoid receptor and
      inhibits the activation of CPP32-like cysteine proteases.
AB  - Glucocorticoid induces apoptosis in immature lymphocytes which is inhibitable by
      Bcl-2. Although glucocorticoid-mediated signal transduction is well understood,
      the mechanism of the induction of apoptosis by the activated glucocorticoid
      receptor as well as the inhibition of apoptosis by Bcl-2 remains enigmatic. Here
      we report that overexpressed Bcl-2 relieves the glucocorticoid receptor-mediated
      repressive function on the AP-1 activity and completely inhibits the activation
      of CPP32-like cysteine proteases. In contrast, glucocorticoid receptor-mediated
      transactivation was not affected by Bcl-2. This suggests that glucocorticoid may
      induce apoptosis by repressing transactivation by AP-1 which is relieved by Bcl
      2. Furthermore, we report evidence that, in contrast with CPP32-like proteases,
      ICE-like proteases are not involved in this apoptotic pathway.

PMID- 9168934
TI  - TNF-alpha mediates inducible nitric oxide synthase expression in human
      neuroblastoma cell line by cisplatin.
AB  - The human neuroblastoma cell line NB-39-nu expressed inducible nitric oxide
      synthase (iNOS) mRNA following treatment with a combination of interferon-gamma
      (IFN-gamma) and cis-diamminedichloroplatinum(II) (cisplatin). The level of iNOS
      mRNA peaked at 48 hr after treatment, and dexamethasone inhibited the induction
      of iNOS mRNA expression. Cisplatin induced tumor necrosis factor-alpha (TNF
      alpha) mRNA expression, and an anti-TNF-alpha neutralizing antibody inhibited the
      induction of iNOS expression by a combination of cisplatin and IFN-gamma in NB-39
      nu cells. Thus, iNOS expression in NB-39-nu cells by a combination of cisplatin
      and IFN-gamma involves in the TNF-alpha-mediated signal transduction mechanism.

PMID- 9168935
TI  - Integration of HTLV-1 provirus into mouse transforming growth factor-alpha gene.
AB  - Human T cell leukemia virus type 1 (HTLV-1) provirus integration was investigated
      in mice inoculated with MT-2 cells, a HTLV-1 producing human T-cell line. From
      spleen DNA derived from a MT-2 cell-injected mouse, we cloned a HTLV-1
      integration site by ligation-mediated PCR. The nucleotide sequence showed that
      HTLV-1 provirus was integrated into an intron of the mouse transforming growth
      factor-alpha gene in the reverse orientation. This result provides for the first
      time molecular evidence that mice can be infected with HTLV-1.

PMID- 9168936
TI  - High shear stress attenuates agonist-induced, glycoprotein IIb/IIIa-mediated
      platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is
      blocked.
AB  - High shear stress facilitates von Willebrand factor (vWF) binding to platelet
      glycoprotein (GP) Ib/IX, causing activation of GPIIb/IIIa to induce platelet
      aggregation. Here we report that activated GPIIb/IIIa, even occupied by ligands,
      is not sufficient to mediate platelet aggregation under high shear stress
      conditions when vWF binding to GPIb/IX is blocked. Platelet rich plasma or washed
      platelet suspension supplemented with purified human fibrinogen at a
      concentration of 2 mg/mL were treated with an anti-vWF monoclonal antibody NMC-4
      which blocks the binding of vWF to GPIb/IX. After addition of 10 mumol/L ADP,
      aggregation was continuously monitored under various shear stress conditions (0
      108 dyne/cm2) using a cone-plate type aggregometer previously described (Ikeda Y
      et al J Clin Invest 1991; 87:1234). The extent of maximal aggregation of agonist
      stimulated platelets in the presence of NMC-4 correlated inversely with the level
      of shear stress applied, with the virtual absence of aggregation at 108 dyne/cm2.
      Once aggregated by 10 mumol/L ADP under low shear stress (12 dyne/cm2), platelets
      could be disaggregated, in part, by the application of high shear stress (108
      dyne/cm2), and reaggregated when shear stress was returned to 12 dyne/cm2. Flow
      cytometric analysis revealed that platelets stimulated with 10 mumol/L ADP at 108
      dyne/cm2 bound fluorescein isothiocyanate (FITC)-labeled fibrinogen, although
      aggregation was absent in this experimental condition. These results demonstrate
      the dual effect of shear stress on platelet functions; a pro-aggregating activity
      that induces vWF-GPIb/IX interaction leading to platelet activation, and an anti
      aggregating force to prevent the growth of platelet thrombi. It is suggested that
      the efficacy of vWF blockade is greater under high shear than low shear stress
      conditions, and that a selective inhibition of platelet functions can be
      possible.

PMID- 9168938
TI  - Transcriptional activation of human LIM-HOX gene, hLH-2, in chronic myelogenous
      leukemia is due to a cis-acting effect of Bcr-Abl.
AB  - DNA methylation plays an important role in gene regulation. A human LIM-HOX gene,
      namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and
      located on chromosome 9q33-34.1, in the same region as the reciprocal
      translocation that creates the Bcr-Abl chimera of Philadelphia chromosome (H.-K.
      Wu et al., 1996, Oncogene 12, 1205-1212). To elucidate the mechanism of hLH-2
      transcriptional activation, we studied the methylation status of hLH-2 in normal
      bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II
      or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH
      2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in
      contrast, both alleles of the hLH-2 locus in CML cells were heavily
      hypomethylated. Furthermore, using a sensitive RT-PCR technique, we examined the
      expression of LH-2 in mouse x human hybrids and a wide array of mouse cell lines
      containing Abl or Bcr-Abl, and we failed to identify a consistent expression
      pattern in the cell lines tested. These results suggest that the transcriptional
      activation of hLH-2 in CML is likely due to a cis-acting effect, but not a trans
      acting effect, of the Bcr-Abl fusion protein. Because hypomethylated genes
      generally are transcribed more efficiently than hypermethylated genes, the high
      level of hLH-2 mRNA in CML cells probably is a consequence of the low level of
      methylation of the gene in the leukemic cells.

PMID- 9168937
TI  - Expression of extracellular calcium-sensing receptor by human lens epithelial
      cells.
AB  - The extracellular calcium-sensing receptor (CaR) confers the capacity to sense
      small changes in the extracellular Ca2+ concentration (Ca2+o) not only upon cells
      involved in maintaining systemic Ca2+ homeostasis but also upon those not
      directly involved in this process. Since high Ca2+o is known to affect various
      physiological processes in lens epithelium both in health and in disease states
      (e.g., the formation of cataracts in hypocalcemic states), we investigated the
      expression and function of the CaR in these cells. By RT-PCR and
      immunocytochemistry the CaR is expressed in human lens epithelial cells in
      culture. In addition, the open state probability of a Ca(2+)-activated potassium
      (K+) channel with a conductance of 82 +/- 3 pS is significantly increased by
      elevating Ca2+o to 3.0 mM or by application of 100 microM neomycin, both
      effective CaR agonists. Therefore, our data suggest that human lens-epithelial
      cells express the CaR, which may be functionally linked to Ca(2+)-activated K+
      channels and, perhaps, to other ion channels involved in ionic homeostasis in the
      lens.

PMID- 9168939
TI  - Regulation of renal vitamin D-24-hydroxylase by phosphate: effects of
      hypophysectomy, growth hormone and insulin-like growth factor I.
AB  - Dietary phosphate (Pi) regulates the production of 1,25-dihydroxyvitamin D3. This
      control is blunted in hypophysectomized (HPX) rats but can be restored by growth
      hormone (GH) or IGF-I. The regulation of the vitamin D catabolism by Pi, GH and
      IGF-I is less clear. In the present study, we found that the activity and
      transcript levels of the catabolic enzyme, vitamin D-24-hydroxylase (24-OHase)
      were decreased 3- and 5-fold, respectively, during Pi restriction in normal rats,
      but this effect is greatly reduced in HPX rats. Examination of the serum
      chemistries revealed that HPX rats on the high Pi diet had lower serum Pi levels
      than normal rats on this diet, presumably due to the known defective reabsorption
      of Pi by HPX rats. Treatment of HPX rats, adapted to a 0.6% P diet, with GH (150
      micrograms) or IGF-I (80 micrograms) suppressed 24-OHase mRNA levels by 88% and
      64%, respectively, by 20 hours and these effects were preceded by decreases in
      serum Pi. Our findings show that the 24-OHase is regulated by dietary Pi and this
      control is modulated by hypophysectomy, GH and IGF-I.

PMID- 9168940
TI  - Demonstration of a leptin binding factor in human serum.
AB  - Serum leptin levels are elevated in subjects with exogenous obesity, indicating
      that obesity is associated with leptin resistance. Since in man no abnormalities
      have yet been found in either the genes for leptin or its receptor, the mechanism
      of leptin resistance in obesity remains unknown. To determine if resistance might
      be related to leptin binding by a serum component, we assessed the carrier status
      of leptin in serum. The presence of a specific leptin binding factor in human
      serum has been established by (1) demonstrating [125I]-leptin binding to a serum
      component that is saturable and specifically displaceable only by unlabeled
      leptin and not by human growth hormone, pork insulin, insulin-like growth factors
      I and II, luteinizing or follicle stimulating hormones, transforming growth
      factor-beta 1, interleukin-6, or leukemia inhibiting factor; (2) fractionating
      the leptin bound serum complex and the serum leptin binding component on a
      molecular sieving column revealing a mass of approximately 450 kDa; and (3)
      identifying an inverse correlation between the concentration of serum leptin and
      the quantity of the leptin binding component. It is suggested that binding of
      leptin by this serum component may influence the physiologic response to leptin.

PMID- 9168941
TI  - Pharmacological characterization and tissue distribution of the human and rat
      GALR1 receptors.
AB  - The diverse biological functions of galanin are mediated via membrane bound high
      affinity receptors. In order to identify and characterize potential galanin
      receptor subtypes, we have examined the specific 125I-galanin binding to the CHP
      212 human neuroblastoma cell line. The galanin receptors expressed in CHP-212
      cells, like GALR1 have high affinity for galanin (Kd = 0.07 nM) and the potency
      for inhibition of 125I-galanin binding by galanin peptides parallels that of
      hGALR1 expressed in a stable CHO cell line. We confirmed that GALR1 is expressed
      in these cells by RT-PCR. We further determined the tissue expression patterns of
      hGALR1 which is expressed in a variety of human tissues at a very low level, with
      the highest levels seen in heart, small intestine and prostate. A species of
      approximately 70 kDa is recognized by antisera specific for hGALR1 by Western
      blot analysis and should allow future measurements of receptor protein
      expression.

PMID- 9168942
TI  - The regulation of membrane cofactor protein (CD46) expression by the 3'
      untranslated region in transgenic mice.
AB  - Regulation of the membrane cofactor protein (MCP: CD46) was examined. While the
      expression of MCP in mice carrying MCP(BC2) cDNA with 125 bp of 3' untranslated
      region (3'UT) was minimal, that in mice carrying MCP cDNA without total 3' UT was
      evident in many organs. Reverse transcriptase polymerase chain reaction (RT-PCR)
      analysis clearly showed the presence of mRNA even in transgenic mice with 3' UT,
      suggesting that the expression was regulated at the post-transcriptional stage.
      The in vitro expression data of MCP molecules on the stable Chinese hamster ovary
      (CHO) cell clone corresponded to that in transgenic mice. The first 125 bp
      downregulated the expression of MCP molecules in combination with not only beta
      actin, but also SR alpha, promoter. Also, this region inhibited expression of
      decay accelerating factor (DAF: CD55) molecules when it was inserted into cDNA of
      DAF. Furthermore, the first 32 bp of the 3' UT revealed the same downregulation
      effect as 125 bp on MCP molecules. These findings indicated that the first 125 bp
      (and the first 32 bp in particular) of 3' UT regulate the expression of MCP
      molecules in transgenic mice.

PMID- 9168943
TI  - Analysis of the mismatch and insertion/deletion binding properties of Thermus
      thermophilus, HB8, MutS.
AB  - The methyl-directed long patch repair pathway in Escherichia coli is involved in
      increasing the fidelity of replication specific repair of DNA polymerase
      incorporation errors. This pathway is mediated by three gene products, MutS,
      MutL, and MutH, which are conserved in higher eukaryotes. Mutations in human
      homologues of these proteins have been shown to be implicated in hereditary non
      polyposis colorectal cancer (HNPCC). A MutS homologue has recently been
      identified in the extremely thermophilic bacterium, Thermus thermophilus. Here we
      describe analysis of the binding properties of this protein, which has indicated
      it can identify all specific base mismatches as well as one, two and three base
      pair insertion/deletion mutations. We therefore believe this protein may be
      generally useful for applications involving mismatch detection.

PMID- 9168944
TI  - Localization of a negative thyroid hormone-response region in hepatic stearoyl
      CoA desaturase gene 1.
AB  - The effect of thyroid hormone on stearoyl-CoA desaturase gene 1 (SCD1) expression
      was investigated in mouse liver. Daily injections of 15 micrograms
      triiodothyronine (T3)/100 g body weight to hypothyroid mice resulted in
      repression of SCD1 mRNA levels by more than 50% in 48 hours and up to 65% in 6
      days. Transient co-transfections were performed with an expression vector for T3
      receptor alpha (T3R alpha) in HepG2 cells using chimeric reporter gene constructs
      of the SCD1 5'-flanking region. Transcriptional repression of the SCD1 putative
      promoter was observed upon treatment with 100 nM T3 when cotransfected with T3R
      alpha, but not without cotransfection of receptor. Transient gene expression
      studies localized a T3 response region to a 70-bp sequence in the SCD1 putative
      promoter. Eliminating the TATA box and an AP-2 binding site, DNA mobility shift
      analysis demonstrated specific binding of in vivo nuclear protein from mouse
      liver nuclear extract to a 43-bp sequence. DNA mobility shift with purified T3R
      alpha confirmed the presence of a T3 receptor binding site in this thyroid
      hormone-responsive region. These data indicate that SCD1 contains a negative T3
      response region in its proximal promoter.

PMID- 9168945
TI  - Characterization of the cloned promoter of the human initiation factor 4AI gene.
AB  - Protein synthesis initiation factor 4AI (eIF-4AI) is ubiquitously expressed in
      eucaryotic cells. We characterized the eIF-4AI gene promoter cloned from human
      fibroblasts. The minimal promoter, localized to a region in the 5'-noncoding
      region adjacent to the first exon, consisted of approximately 300 base pairs
      (bp), 80% of which were identical with those in the corresponding mouse promoter.
      The minimal promoter contained TATA and CAAT motifs and consensus sequences
      binding to SP1 (three sites) and AP2 (one site). Deletion analyses of the
      promoter revealed that a 24-bp region near 5'-end of the minimal promoter was
      essential for the efficient transcription, although the AP2 site in the region
      was dispensable. A fluorescence polarization assay suggested that the plus strand
      of the 24-bp region, despite the lack of known consensus sequences binding to
      transcription factors except for AP2, bound to unknown nuclear protein(s) in a
      sequence specific manner.

PMID- 9168946
TI  - Bacterial scavengase p20 is structurally and functionally related to
      peroxiredoxins.
AB  - Scavengase p20 was recently identified as a novel family of bacterial antioxidant
      enzymes possessing thioredoxin-linked thiol peroxidase activity. In this study,
      the Escherichia coli gene coding for scavengase p20 was isolated from three
      different strains and the nucleotide sequence was determined. Multiple alignment
      of amino acid sequence revealed that a previously unidentified Cys-61 is most
      conserved among all bacterial p20 scavengases and corresponds to the active site
      in the well-characterized peroxiredoxins. Phylogenetic analysis further supported
      that scavengase p20 is a novel subfamily of peroxiredoxins. Site-directed
      mutagenesis studies demonstrated that Cys-61 is indispensable for the antioxidant
      activities of scavengase p20. Taken together, our findings strongly suggest that
      the p20 scavengases are structurally and functionally related to peroxiredoxins.

PMID- 9168947
TI  - Method for identifying ligands activating either excitatory or inhibitory G
      protein-coupled receptors by functional coexpression in Xenopus oocytes.
AB  - Xenopus oocytes devoid of their follicular enclosure provide a frequently used
      expression system for investigating receptors that transduce through activation
      of adenylyl cyclase following injection of the appropriate mRNA. However, due to
      a low basal activity of the cyclase they cannot be utilized to investigate
      receptor-mediated reductions in endogenous cAMP levels. In order to overcome this
      limitation, a model was designed in which test clones for such inhibitory
      receptors were co-expressed with a beta 2-adrenoceptor, which elevated cAMP upon
      exposure to isoproterenol. Following injection of mRNA to express the alpha 2
      test receptor in the oocytes, marked reduction in cAMP could be measured after
      exposure to clonidine. Attenuation of cAMP levels was also seen following co
      expression of the dopamine D2 receptor along with dopamine administration. Thus,
      after inducing a receptor-mediated tone in adenylyl cyclase activity, Xenopus
      oocytes can be conveniently used to study also ligands that bind to inhibitory G
      protein coupled receptors.

PMID- 9168948
TI  - Side-chain specificity at three temperature-sensitive folding mutation sites of
      P22 tailspike protein.
AB  - The phage P22 tailspike protein is one of the few proteins for which both in vivo
      and in vitro folding pathways have been thoroughly characterized. Many
      temperature-sensitive folding (tsf) mutations that cause the mutant tailspike
      polypeptides not to be folded at high restrictive temperatures have been
      identified. One-third of the tsf mutation sites are located in one domain called
      the dorsal fin domain (residues 197-259), which protrudes on the solvent-exposed
      side of the main beta helix. In the present study, we introduced various amino
      acid substitutions at three tsf mutation sites (residue numbers 235, 238, and
      244) in this domain to elucidate the mechanism of these tsf mutations in detail.
      The side-chain specificity at these tsf sites, together with structural
      examination in the tertiary fold, strongly suggests that destabilization of
      folding intermediates by loss of specific interactions is likely to be the major
      cause of the tsf defect in the dorsal fin domain.

PMID- 9168949
TI  - Differential localization of G-proteins, G alpha o and G alpha i-1, -2, and -3,
      in polarized epithelial MDCK cells.
AB  - MDCK cells were stably transfected with rat G alpha o cDNA and confluent
      polarized monolayers were analyzed by immunocytochemistry to compare the
      intracellular targeting of G alpha o with the localization of the endogenously
      expressed G alpha i subunits. Immunofluorescence confocal microscopy showed that
      G alpha o is targeted strictly to the lateral membrane. Immunolocalization of G
      alpha i-1, -2, and -3 showed that G alpha i-1 and -2 are confined to the
      cytoplasm and G alpha i-3 is found on the lateral membrane, in the cytoplasm, and
      faintly on the apical surface of these cells. Thus, the different pertussis toxin
      sensitive G-proteins are differentially localized in polarized epithelial cells.

PMID- 9168950
TI  - Activation of Met tyrosine kinase by hepatocyte growth factor is essential for
      internal organogenesis in Xenopus embryo.
AB  - Hepatocyte growth factor (HGF) specifically activates Met tyrosine kinase
      receptor, leading to mitogenic, motogenic, and morphogenic responses in a wide
      variety of cells. To know a role of HGF in Xenopus embryogenesis, loss-of
      function mutation was introduced by dominant expression of truncated tyrosine
      kinase-negative Met. When tyrosine kinase-negative Met mRNA was micro-injected
      into two-cell to eight-cell stages Xenopus embryos, the liver development was
      mostly impaired and structures of pronephros and the gut were grossly
      underdeveloped in the restricted, late stage of development. These results
      strongly suggest that functional coupling between HGF and Met is essential for
      the development of internal organs originated from primitive gut and possibly
      involved in embryonic skeletogenesis. Together with developmental abnormality in
      mice mutated with HGF or Met gene, essential role of HGF for liver development is
      highly conserved from amphibian to mammalian species.

PMID- 9168951
TI  - Cytoplasmic gene expression system enhances the efficiency of cationic liposome
      mediated in vivo gene transfer into mouse brain.
AB  - Development of methodologies for gene transfer into the central nervous system
      (CNS) is important for fundamental research as well as clinical studies for gene
      therapy. Cationic liposomes (CL) are attractive vectors because of their safety
      and ease of use. However, to date only low rates of success have been reported.
      We succeeded in obtaining high transfection efficiencies into the newborn mouse
      brain in vivo by CL and a cytoplasmic gene expression system based on T7 RNA
      polymerase and T7 RNA polymerase- and the luciferase-gene with the T7 promoter
      sequence. This system showed an efficiency rate 2 orders of magnitude higher than
      the standard system, which used CL and luciferase genes with a Rous sarcoma virus
      promoter, pRSVL. In addition, in vitro experiments using LLCMK2 cells showed that
      cytoplasmic gene expression occurred rapidly (within 6 h) after transfection. In
      contrast, pRSVL required 24-48 h for induction of luciferase expression. Our
      results suggest that the cytoplasmic gene expression system is useful for gene
      delivery into the CNS.

PMID- 9168952
TI  - Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM
      1 expression in human endothelial cells.
AB  - Most studies on the antipsoriatic mode of action of dimethylfumarate focused on
      its antiproliferative effects in keratinocytes. Because inflammatory skin
      diseases are associated with an upregulation of endothelial cell adhesion
      molecules and because the presence of inflammatory cells in dermis and epidermis
      is considered an important feature in psoriasis, we tested the effect of DMF on
      cytokine-induced adhesion molecule expression in HUVEC, using in situ ELISA and
      Northern blotting. Dimethylfumarate inhibited ICAM-1, VCAM-1, and E-selectin
      expression and reduced adhesion of U937 cells to stimulated HUVEC.
      Monoethylfumarate and fumaric acid had no effect. Similar inhibitory effects for
      DMF on VCAM-1 expression were observed after stimulation of HUVEC with LPS, PMA,
      IL-4, and IL-1 alpha or in combinations with TNF alpha. These data are in
      agreement with previously reported effects of DMF on intracellular thiol levels
      and inhibition of NF-kappa B activation. The inhibitory effect on cytokine
      induced endothelial adhesion molecule expression may represent another target of
      dimethylfumarate in psoriasis.

PMID- 9168953
TI  - Identification and characterization of a constitutive HSP75 in sea urchin
      embryos.
AB  - An antiserum against a hsp of the 70-kDa family was prepared, by means of a
      fusion protein, which was able to detect a constitutive 75-kDa hsc in the sea
      urchin P. lividus. This hsc was present both during oogenesis and at all
      developmental stages. A two-dimensional electrophoresis has revealed four
      isolectric forms of this 75-kDa hsc. The amino acid sequence of the fragment used
      to prepare the anti-hsp70 antibodies revealed a 43% identity with the
      corresponding part of sea urchin sperm receptor, and in mature eggs a brighter
      immunofluorescence was seen all around the cell cortex where the receptor for sea
      urchin sperm is localized. In oocytes the hsp75 was localized in the cytoplasms
      but not in the nuclei. In the embryos a higher hsp75 concentration was found in
      the portion facing the lumen of the cells which invaginate at gastrulation.

PMID- 9168954
TI  - Electrophysiological responses to oxytocin and ATP in monolayers of a human sweat
      gland cell line.
AB  - It was shown that oxytocin (OT) elicits electrophysiological responses in
      cultured monolayers of NCL-SG3, a human immortalized sweat gland cell line. The
      response to OT was greater for basal applications. It was also found that
      monolayers respond to ATP with a transient transepithelial-potential change, with
      a more pronounced response to apical than to basal applications. The IC50 for the
      response to OT was 180 nM at room temperature. The response to OT was not due to
      effects of OT on vasopressin (AVP) receptors as evidenced by three tests: (a) The
      response was completely blocked by the selective OT-receptor antagonist [Mpa1,D
      Tyr(Et)2,Thr4,Orn8]-OT (CAP) applied at equal concentrations (100-1000 nM) to
      that of OT. (b) The response to OT was similar to that of ionomycin (2 microM) or
      ATP (150 microM). In contrast, the response to AVP (500 nM) or cAMP (2 mM) were
      smaller and of a different time course. (c) OT increased but AVP had no effect on
      the intracellular free calcium. It is suggested that OT may have a role in the
      regulation of salt balance in sweating.

PMID- 9168955
TI  - Vascular effects of L-arginine: anything beyond a substrate for the NO-synthase?
AB  - L-arginine supplementation is hypothesized to reduce endothelial dysfunction and
      atherogenesis via increased biosynthesis of nitric oxide. Here we describe
      superoxide scavenging properties of arginine as an additional aspect which needs
      to be considered. Furthermore, arginine reduced copper-induced lipid
      peroxidation, indicating that superoxide anions essentially contribute to this
      process. In intact endothelial cells, L-arginine but not D-arginine diminished
      superoxide release and reduced cell-mediated breakdown of nitric oxide. Our data
      indicate that the reported vascular effects of L-arginine supplementation might
      involve an increased bioavailability of nitric oxide due to its superoxide
      scavenging properties beside a potential increased NO biosynthesis.

PMID- 9168956
TI  - Mitochondrial mutations impair signal transduction in Dictyostelium discoideum
      slugs.
AB  - Subpopulations of mutant mitochondria appear to play important roles in
      degenerative processes associated with aging and are characteristic of many
      mitochondrial diseases. We have generated mutants carrying plasmid insertions in
      the Dictyostelium discoideum mitochondrial genome and have shown that phototaxis
      and thermotaxis in these mutants is more sensitive than growth and division to
      the presence of a subpopulation of defective mitochondria. This could result from
      direct impairment of a mitochondrial role in signal transduction, or indirectly
      from the effects of energy depletion. Either way, signal transduction may be the
      first cellular activity to be compromised by the accumulation of defective
      mitochondria in age-related tissue dysfunction and in mitochondrial disease.

PMID- 9168957
TI  - Proliferation of mouse fibroblasts induced by 1,2-dimethylhydrazine auto
      oxidation: role of iron and free radicals.
AB  - Activation of 1,2-dimethylhydrazine (DMH) by prolonged auto-oxidation (24-h)
      induced proliferation of mouse fibroblasts at low hydrazine concentrations (0.1
      1.0 mM) as determined by [3H-methyl]-thymidine uptake of confluent quiescent
      cells. Incubations were performed under conditions in which alkyl radicals are
      slowly formed by DMH auto-oxidation. The proliferative stimulus induced by DMH
      auto-oxidation complements that induced by insulin, PMA, and EGF. Inhibition by
      the iron chelators, o-phenanthroline and desferrioxamine, demonstrates that the
      induction of the proliferative effect is dependent on simple iron complexes.
      Proliferation was also inhibited by superoxide dismutase, catalase, and mannitol,
      implicating reactive oxygen species, although superoxide dismutase and catalase
      also inhibited alkyl radical formation, as determined by spin-trapping. These
      results suggest that cell proliferation induced by DMH auto-oxidation is mediated
      by reactive oxygen species, mainly the hydroxyl radical, and is dependent on
      simple iron complexes, possibly involving the Fenton reaction.

PMID- 9168959
TI  - A nonglycosylated, 68-kDa alpha-L-fucosidase is bound to the mollusc bivalve Unio
      elongatulus sperm plasma membrane and differs from a glycosylated 56-kDa form
      present in the seminal fluid.
AB  - The male reproductive system of the mollusc bivalve Unio elongatulus contains two
      distinct forms of alpha-L-fucosidase, one present in the gonad fluid and a second
      one associated with the sperm plasma membrane. Both activities were purified to
      homogeneity. The soluble seminal plasma enzyme had an oligomeric MW of 56 kDa as
      determined by MALDI-TOF mass spectrometry, whereas the enzyme purified from sperm
      plasma membranes had an MW of 68 kDa. Analyzed by lectin blotting with ConA and
      PNA, the 68 kDa enzyme did not bind either lectin, whereas the 56 kDa form bound
      ConA only. Both fucosidases followed a Michaelis-Menten kinetics with the K(m) of
      the sperm-bound enzyme being 7.1 x 10(-4) M and that of the seminal enzyme being
      9.1 x 10(-4) M. Both had a pH optimum of 5.0.

PMID- 9168958
TI  - Cloning of a cDNA encoding a novel importin-alpha homologue, Qip1: discrimination
      of Qip1 and Rch1 from hSrp1 by their ability to interact with DNA helicase
      Q1/RecQL.
AB  - We isolated two cDNA clones encoding human proteins which interact with DNA
      helicase Q1/RecQL, a human homologue of Eschelichia coli RecQ protein, by two
      hybrid screening. One of these proteins, named Qip1, was a novel protein
      homologous to the nuclear localization signal (NLS) receptor importin-alpha, and
      the other was the known protein Rch1, which is also a homologue of importin
      alpha. DNA helicase Q1 in human cell lysates was coprecipitated with bacterially
      expressed Qip1 and Rch1 fused with glutathione-S-transferase with glutathione
      Sepharose beads, confirming the interaction between these proteins and DNA
      helicase Q1. Two-hybrid experiments revealed that Qip1 interacted with the NLS of
      SV40 T antigen similar to Rch1 and hSrp1. In addition, interaction of the
      putative NLS in DNA helicase Q1 with Qip1 and Rch1 but not with hSrp1 was
      confirmed by the two-hybrid system.

PMID- 9168960
TI  - Expression of PrP mRNA is regulated by a fragment of MRP8 in human fibroblasts.
AB  - Prion protein (PrPc) is expressed in many tissues, both in human and animals. The
      scrapie isoform of PrPc has been shown to cause neurodegeneration. In other
      studies it has been demonstrated that overexpression of the PrP gene can result
      in nonneuronal tissue degradation. Little is known, however, about the normal
      function of PrPc and prion protein gene regulation. Using cultured periodontal
      ligament cells as an experimental model, we have demonstrated the stimulation of
      PrP mRNA expression by MRP8 (migration inhibitory factor-related protein).
      Additionally, we have shown that PDGF has an opposite effect acting as a
      suppresser. We propose that a correlation exists between PrPc mRNA expression and
      cell growth arrest and differentiation.

PMID- 9168961
TI  - Selective clinical ultrasound signals mediate differential gene transfer and
      expression in two human prostate cancer cell lines: LnCap and PC-3.
AB  - Low intensity ultrasound signals, similar to that employed in clinical therapy,
      are found to mediate differential gene transfer and expression of the Green
      Fluorescence Protein (GFP) reporter in two human prostate cancer cell lines,
      LnCap and PC-3. Cell suspensions in the presence or in the absence of GFP
      (44.5nM) were treated at 37 degrees C under a standing wave condition. Cells were
      exposed to either continuous wave, 932.7kHz ultrasound, or to several independent
      bursts, each burst comprising a 20% duty cycle (932.7kHz) sine wave. The burst
      "repetition" frequency was varied from 10Hz to 10kHz in several different
      experiments and each treatment received a net identical ultrasound energy
      exposure. Transient GFP expression levels in viable cells were monitored by flow
      cytometry. The findings revealed a strong ultrasound tone-burst frequency
      dependence on the transfection efficiencies. Interestingly, the ultrasound signal
      parameters which are routinely employed in clinical therapy did not yield any
      statistically significant enhancement in transfection efficiency relative to
      their sham counterparts.

PMID- 9168962
TI  - The Golgi sialoglycoprotein MG160, expressed in Pichia pastoris, does not require
      complex carbohydrates and sialic acid for secretion and basic fibroblast growth
      factor binding.
AB  - MG160, a type I membrane sialoglycoprotein of the medial cisternae of the rat
      Golgi apparatus, shows high homology (over 90%) with CFR, a fibroblast growth
      factor receptor, and ESL-1, an E-selectin ligand of the cell surface of murine
      myeloid cells. When Chinese Hamster Ovary (CHO) cells were stably transfected
      with a cDNA lacking the transmembrane and C-terminus cytoplasmic domain of MG160
      (delta TMCT), a fully processed protein of 160 kDa apparent molecular mass was
      recovered in the culture medium. When these cells were treated with tunicymycin,
      a 130- to 140-kDa protein was immunoprecipitated from the culture medium. A
      construct lacking the signal sequence, the single transmembrane, and the
      cytoplasmic domains of MG160 (delta TMCT-) was integrated at the HIS Pichia
      pastoris genome site using the expression vector pPIC 9 which possesses a yeast
      compatible signal sequence (Invitrogen). Recombinant protein accumulated in the
      medium to approximately 10 mg/L. The yeast recombinant protein lacked complex
      carbohydrates and sialic acid but bound 125I bFGF. Similarly, rat MG160 subjected
      to deglycosylation by peptide:N-glycosidase F (PNGase) bound 125I bFGF.

PMID- 9168963
TI  - Stalling of human methyltransferase at single-strand conformers from the
      Huntington's locus.
AB  - We describe evidence for a sequence of events in which the Human DNA(cytosine
      5)methyl-transferase first methylates spontaneous single-stranded conformers
      (SSCs) and then stalls at the methylated site to produce a complex with the
      conformationally unusual DNA. This property of the enzyme is a result of its
      ability to respond to a general loss of symmetry at its CG recognition site. The
      data suggest that DNA methyltransferase, itself, may physically participate in
      biological processes that distinguish between DNA that is in the normal Watson
      Crick paired conformation and DNA that is conformationally unusual (e.g. a
      hairpin loop or misassembled replication intermediate). The in vitro methylation
      of spontaneous SSCs from the Huntington's locus illustrates the phenomenon.

PMID- 9168964
TI  - Ascorbate stabilization is stimulated in rho(0)HL-60 cells by CoQ10 increase at
      the plasma membrane.
AB  - Long-term treatment with ethidium bromide of HL-60 cells induced a mitochondria
      deficient rho degree cell line, where mitochondrial DNA can not be identified by
      PCR and cytochrome c oxidase activity was 80% decreased. These cells showed a
      progressive increase of ascorbate stabilization which was 52% higher in the
      established rho degree HL-60 cells. Both CoQ10 and NADH-ascorbate free radical
      reductase of the plasma membrane were increased in rho(0)HL-60 cells compared to
      parental cells, while NADH-cytochrome c reductase was unchanged. CoQ10 is a
      component of the ascorbate stabilization activity in the plasma membrane that
      would provide both a mechanism to deplete the excess of NADH produced in rho(0)HL
      60 cells and for resistance to oxidative stress.

PMID- 9168965
TI  - Oxidative modification of tryptophan residues exposed to peroxynitrite.
AB  - The aim of this study was to clarify the mechanism of loss of Trp residues in
      proteins exposed to peroxynitrite. The Trp residues in bovine serum albumin and
      collagen IV were decreased by peroxynitrite treatment. To identify the
      degradation products of the Trp residue by peroxynitrite, tert-butoxycarbonyl-L
      tryptophan (Boc-Trp) was used as a model of the Trp residue in proteins, and the
      products formed from peroxynitrite-treated Boc-Trp were then isolated. Boc-Trp
      decreased with an increase in peroxynitrite concentration. N-Formylkynurenine,
      oxindole, and hydropyrroloindole were identified as major products. The formation
      of these products may account for the losses of Trp residues in proteins by
      peroxynitrite.

PMID- 9168966
TI  - Alternate COX-2 transcripts are differentially regulated: implications for post
      transcriptional control.
AB  - Prostaglandin (PG) synthesis during inflammation occurs mainly via the
      transcriptionally regulated cyclooxygenase, COX-2. In pulmonary type II A549
      cells, Northern analysis identified multiple IL-1 beta-inducible COX-2 mRNA
      transcripts. Amplification of 3'-cDNA ends by anchored PCR revealed products
      corresponding to the predominant 4.5 and 2.7 kb transcripts. Sequence analysis of
      amplification products indicated that these transcripts arose by alternate
      consensus and non-consensus polyadenylation site usage. The predominant 4.5 kb
      transcript showed a half-life in excess of two hours that was further stabilized
      by IL-1 beta. In addition, the COX-2 3'-untranslated region (UTR), which contains
      22 copies of the putative RNA instability motif, AUUUA, when cloned downstream of
      a constitutively expressed luciferase gene, was found to confer partial IL-1 beta
      responsiveness in LA-4 cells. Finally, in vivo in LPS-treated rats, differential
      expression of similar COX-2 mRNA isoforms was also observed. Taken together these
      data suggest a functional role for post-transcriptional mechanisms, including
      alternate polyadenylation, in the control of COX-2.

PMID- 9168967
TI  - Identification of a unique monocarboxylate transporter (MCT3) in retinal pigment
      epithelium.
AB  - The retinal pigment epithelium transports lactate between two tissue
      compartments, the interphotoreceptor matrix and the choriocapillaris. In this
      report we describe a 2.45-kb cDNA isolated from a chick cDNA RPE library that
      encodes a membrane protein found only in RPE cells. The deduced protein has 542
      amino acids with twelve putative membrane spanning domains. The cDNA has been
      designated MCT3 based on its 45% identity in amino acid sequence and structural
      similarity with the monocarboxylate transporters MCT1 and MCT2. Stable
      transfectants (pCl-neo/MCT3), made in a rat thyroid epithelial cell line (FRTL
      5), express MCT3 RNA. Transfectants had enhanced pyruvate uptake (used as a
      measure of lactate uptake) which was proton-dependent and inhibited by alpha
      cyano-4-hydroxycinnamate. In summary, MCT3's unique expression in RPE cells,
      multiple potential phosphorylation sites, and basolateral distribution suggest
      that MCT3 may regulate lactate levels in the interphotoreceptor space.

PMID- 9168968
TI  - Cloning and sequence analysis of the DNA polymerase alpha gene of Leishmania
      donovani: comparison with the human homologue.
AB  - The gene encoding the DNA polymerase alpha catalytic subunit of the kinetoplastid
      parasite L. donovani has been isolated, sequenced and compared with other
      eukaryotic homologues. The coding region is 4020 bp in length and specifies an
      inferred protein sequence of 1339 amino acids (aa). There is a high level of
      variability between the human and L. donovani gene sequences, but functional
      substrate-binding residues identified in humans and yeast appear to also be
      conserved in this parasite. The discovery of a cysteine-rich region located in
      the midst of the active sites of the enzyme, which appears to be unique to the
      Kinetoplastids, and aa differences found between some of the conserved regions
      implicated in catalytic function, may aid in drug design. The putative DNA
      binding Zn finger at the C-terminus of the protein appears highly species
      specific and may have potential as a drug target for blocking enzyme catalysis in
      the parasite.

PMID- 9168969
TI  - Molecular cloning and characterization of a cDNA for the highly conserved HMG
      like protein (Pf16) gene of Plasmodium falciparum.
AB  - A cDNA clone (PfHB3-2-4) of 1538 bp corresponding to the highly conserved HMG
      like protein (Pf16) was isolated. However, northern analysis suggests that the
      mRNA is about 2.2 to 2.3 kb. Analysis by RT-PCR indicated that the 0.6 to 0.7 kb
      sequence missing in the cDNA maps to the 3' end, suggesting that the cDNA is
      terminated within the 26 adenosine residues that are in the middle of the Pf16
      sequence. The most unique feature about this cDNA is the presence of two open
      reading frames (ORF), one from nucleotides 91 to 927 and the other starting from
      1421. The second ORF corresponds to Pf16. Expression of the cDNA clones in
      Escherichia coli and translation in rabbit reticulocytes of RNA transcribed from
      the T7 promoter of the cDNA clones revealed that only the 3' end Pf16 is
      translated from this mRNA. Further experiments with antisense oligonucleotides
      specific for Pf16 indicated that the Pf16 protein serves an important function in
      the life cycle of the parasite.

PMID- 9168970
TI  - Genetic and physical delineation of the region of the mouse deafness mutation
      shaker-2.
AB  - A total of 951 backcross progeny have been obtained from a backcross segregating
      for the mouse deafness mutation, shaker-2(sh-2). Linkage analysis provides a
      detailed genetic map in the vicinity of sh-2 which comprises 40 backcross mice
      identified as recombinant within a 4 cM region. This allows construction of a
      contig consisting of 21 BAC clones across an approximately 700-kb region of sh-2.
      This covers the entire nonrecombinant region of sh-2 and is therefore useful to
      facilitate the identification of genes in the sh-2 region.

PMID- 9168971
TI  - Conformational adaptation of annexin V upon binding to liposomes: a time-resolved
      fluorescence study.
AB  - The fluorescence intensity decay of the single tryptophan residue, Trp-187, of
      free annexin V is described by the sum of three lifetime components (5.4, 1.3,
      and 0.4 ns), which may be correlated to three ground-state classes of Trp
      conformers. The two major classes (44 and 48%) are embedded in the protein
      matrix. When annexin V binds to calcium and liposomes made of
      dioleoylphosphatidylcholine and dioleoylphosphatidylserine, similar results are
      obtained whatever the (10-200) lipid ratio. The Trp fluorescence decay is fitted
      with only two components (6.9-7.2 and 2.0-2.2 ns). Decay-associated spectra
      reveal that the longest lifetime of bound annexin V can be related to Trp
      residues (60%) located in a partially polar environment, which could correspond
      to the protein-membrane interface. The shortest lifetime is attributed to Trp
      residues (40%) which reside in a hydrophobic surrounding: these Trp residues
      would penetrate into the phospholipid membrane and contribute to the
      stabilization of the 2D-array of annexin V molecules.

PMID- 9168972
TI  - In vitro selection of DNA to chloroaromatics using magnetic microbead-based
      affinity separation and fluorescence detection.
AB  - In vitro selection (SELEX) of DNA ligands to the chloroaromatics, 4-chloroaniline
      (4-CA), 2,4,6-trichloroaniline (TCA) and pentachlorophenol (PCP), was performed
      by a novel method utilizing magnetic beads (MBs) having a linker arm for
      immobilization. Use of MBs was advantageous in obviating elution and
      precipitation of DNA as conjugated MBs with surface-captured template DNA could
      be directly added to PCR mixtures. In addition, a simplified PCR scheme requiring
      only one type of primer and a rapid fluorescence microscopic method for assessing
      nucleic acid binding after each round of SELEX were demonstrated.

PMID- 9168973
TI  - Sphingosine-1-phosphate mobilizes intracellular calcium and activates
      transcription factor NF-kappa B in U937 cells.
AB  - Sphingosine-1-phosphate (SPP), a metabolite of sphingolipids, has been implicated
      as a second messenger in cell growth regulation and signal transduction via
      calcium mobilization from internal stores. This study shows that SPP mobilizes
      intracellular calcium in U937 cells and demonstrates for the first time the
      ability of SPP to activate the transcription factor NF-kappa B in these cells.
      Furthermore, calcium release from the internal stores by thapsigargin (TG), an
      inhibitor of the endoplasmic reticulum Ca2+ pump, was associated with activation
      of NF-kappa B. Moreover, we have shown that while an intracellular calcium
      chelator BAPTA/AM was able to inhibit both SPP- and TG-induced NF-kappa B
      activation, it had no effect on TNF-induced NF-kappa B activation. In addition,
      SPP-induced NF-kappa B activation was blocked both by cyclosporin A, known to
      inhibit calcineurin phosphatase activity, and by the antioxidant butylated
      hydroxyanisole. These observations suggest that intracellular calcium
      mobilization is required for SPP-induced NF-kappa B activation, which may involve
      calcineurin- and redox-dependent mechanisms.

PMID- 9168974
TI  - 1 alpha,25-(OH)2-vitamin D3 stimulates the adenylyl cyclase pathway in muscle
      cells by a GTP-dependent mechanism which presumably involves phosphorylation of G
      alpha i.
AB  - To further understand the mechanism underlying 1,25(OH)2D3 activation of the cAMP
      pathway, the effect of the hormone on adenylyl cyclase (AC), GTPase and protein
      kinase A (PKA) activities as well as on the phosphorylation of G alpha i was
      studied in membranes from chick skeletal muscle cells. The sterol stimulated AC
      activity in a dose (0.1-10 nM) and time (1-5 min.) dependent fashion, provided
      GTP (10 microM) was present in the assay. High affinity GTPase activity was
      unaffected by the hormone. In the absence of GTP or in the presence of Mn2+ (20
      mM), 1,25(OH)2D3 effects on AC were abolished. PKA activity was increased (+120%)
      in cells pretreated (1 nM, 5 min.) with the sterol. Moreover, immunoprecipitation
      of G alpha i from [32P]-labeled myoblast membranes showed that 5 min. exposure to
      1 nM 1,25(OH)2D3 increased (1.5-2 fold) the phosphorylation of its alpha subunit.
      The present data suggest that in muscle cells, 1,25(OH)2D3 activates AC by a non
      direct, GTP-dependent action which could imply amelioration of Gi function by
      sterol-induced alpha i phosphorylation.

PMID- 9168975
TI  - The unusual stability of saporin, a candidate for the synthesis of immunotoxins.
AB  - Saporin, a monomeric protein extracted from the seeds of Saponaria officinalis,
      is an enzyme capable of specific depurination of the eukaryotic ribosomes.
      Because of its toxicity, saporin proved useful for the synthesis of immunotoxins,
      chimeric conjugates of a toxin and an antibody specifically directed against
      cancer cells or other targets. In this paper we report a study of the structural
      properties of saporin in the presence of denaturing agents and/or proteolytic
      enzymes. We found that saporin is extremely resistant to denaturation by urea or
      guanidine (up to 4 M), even at relatively high temperature (up to 55 degrees C).
      Moreover a structural change detected as a reduction of the fluorescence emission
      of the single Trp residue is reversible and is not paralleled by changes of the
      far UV CD spectrum, suggesting that even under harsh experimental conditions
      unfolding is limited. In good agreement with these results, guanidine-treated
      saporin is not attacked by proteolytic enzymes. The remarkable resistance of
      saporin to denaturation and proteolysis suggests this protein as an ideal
      candidate for biotechnological applications.

PMID- 9168976
TI  - Perturbation of cellular calcium delays the secretion and alters the
      glycosylation of thyroglobulin in FRTL-5 cells.
AB  - Treatment of FRTL-5 cells with a Ca2+ ionophore, A23187, or a specific inhibitor
      of the endoplasmic reticulum Ca2+ ATPases, thapsigargin, delayed thyroglobulin
      secretion. The secreted thyroglobulin showed an increased electrophoretic
      mobility and a reduced sensitivity to neuraminidase. Only thyroglobulin that was
      still in the endoplasmic reticulum was sensitive to the Ca(2+)-perturbant drugs
      as shown by experiments in which the drugs were added at different times during a
      chase. Analysis of the carbohydrate chains by BioGel P4 showed that thyroglobulin
      secreted in the presence of the Ca(2+)-perturbants displayed an increased ratio
      high mannose/complex chains.

PMID- 9168977
TI  - Isolation of a novel cytokine from human fibroblasts that specifically inhibits
      osteoclastogenesis.
AB  - A factor which inhibits osteoclast-like cell formation was found in the
      conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor,
      termed osteoclastogenesis inhibitory factor, OCIF, was purified to homogeneity.
      OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer
      with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of
      120,000. The N-terminus of OCIF is blocked and the determination of internal
      amino acid sequences revealed that OCIF has no homology to known proteins. OCIF
      inhibited in a dose-dependent manner osteoclastogenesis elicited through three
      distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D3,
      parathyroid hormone, and interleukin-11, respectively, in a dose range of 1 to 40
      ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone resorption by mature
      osteoclasts nor exerts any other biological activities. These data strongly
      suggest that OCIF is a novel cytokine which specifically inhibits
      osteoclastogenesis.

PMID- 9168978
TI  - Identification and characterization of MARCKS in Xenopus laevis.
AB  - MARCKS proteins are widely distributed in mammalian cells and subserve an
      important role as probes in the examination of signal transduction processes
      because they are specific endogenous phosphoreceptors for activated protein
      kinase C. Experiments were performed to determine whether MARCKS proteins are
      present in amphibia and to show their usefulness as substrates for stimulated PKC
      activation, using cultured renal epithelial cells (A6) derived from Xenopus
      laevis as an experimental model.

PMID- 9168979
TI  - Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf)
      antibody GUR76-23 which inhibits vWf interaction with alpha IIb beta 3 but not
      alpha v beta 3 integrin.
AB  - von Willebrand factor (vWf) is known to interact with the two beta 3 integrins,
      alpha IIb beta 3 and alpha v beta 3, in an RGD-dependent manner. We characterized
      a novel murine monoclonal antibody to human vWf, GUR76-23, which recognized a
      site within the carboxy-terminal half of the molecule containing the RGD
      sequence. This antibody inhibited high shear-induced platelet aggregation and
      blocked adhesion of ADP plus epinephrine-stimulated platelets to vWf, indicating
      that it interferes with the interaction with alpha IIb beta 3. Unlike antibodies
      against the RGD site, however, the antibody was without effect on adhesion of
      cultured human umbilical vein endothelial cells to vWf, a phenomenon known to
      involve the interaction with alpha v beta 3. GUR76-23 binding was not displaced
      by anti-RGD antibodies. These results suggest that the adhesive interaction of
      vWf with these two beta 3 integrins may be differentially modulated by a site(s)
      other than the common RGD module.

PMID- 9168980
TI  - Identification of human semaphorin E gene expression in rheumatoid synovial cells
      by mRNA differential display.
AB  - Rheumatoid arthritis (RA) is characterised by chronic inflammation of synovial
      tissue with aggressive proliferation of synovial cells causing destruction of
      cartilage and bone. Immunopathological mechanisms, infectious causes and genetic
      factors have been discussed, but the etiology of the disease has not been
      understood until now. Especially, the mechanisms driving tumourlike growth and
      invasive behaviour of fibroblastoid synovial cells have not been identified yet.
      Our aim is to find cellular factors which are mediators for such pathways. One
      possibility to approach this, is searching for disease-relevant genes. We applied
      the mRNA-differential display technique to compare mRNA expression patterns of
      normal and rheumatic synovial fibroblasts. We identified an upregulation of the
      human semaphorin E gene in rheumatoid synovial fibroblastoid cells. Interestingly
      semaphorin E is a member of a protein-family described to play an
      immunosuppressive role via inhibition cytokines. A relevance of this finding
      towards the pathogenesis of RA is discussed.

PMID- 9168981
TI  - A dtsR gene-disrupted mutant of Brevibacterium lactofermentum requires fatty
      acids for growth and efficiently produces L-glutamate in the presence of an
      excess of biotin.
AB  - A dtsR gene encoding a homolog of the beta subunit of some biotin-containing
      enzymes suppresses a detergent-sensitive mutation of Brevibacterium
      lactofermentum (E. Kimura et al., 1996, Biosci. Biotech. Biochem. 60, 1565-1570),
      which has been used for the fermentative production of L-glutamate. When the dtsR
      gene was disrupted, the organism exhibited strict fatty acid auxotrophy; oleate
      or oleate ester, but not palmitate ester or stearate ester, supported the growth
      of the delta dtsR mutant. Immunoblotting with an anti-DtsR antibody revealed that
      no intact DtsR was present in the cytosol of the delta dtsR mutant. In the
      presence of an excess of biotin, the wild type strain did not produce L-glutamate
      whereas the delta dtsR mutant efficiently produced it. The mechanism underlying
      the efficient production of L-glutamate by the delta dtsR mutant is discussed as
      to the possible role of dtsR in fatty acid metabolism.

PMID- 9168982
TI  - Irreversible metabolic transitions: the glucose 6-phosphate metabolism in yeast
      cell-free extracts.
AB  - The steady-state and dynamic behavior of a partial glycolytic reaction sequence
      are investigated in cell-free extracts of yeast. Pyruvate kinase, adenylate
      kinase and glucose 6-phosphate isomerase cooperate to a multienzyme system
      centered around the 6-phosphofructokinase (6-PFK) and fructose 1,6-bisphosphatase
      (FBPase) cycle. The reaction system operates under thermodynamically open
      conditions maintained by a continuous supply of substrates, i.e., glucose 6
      phosphate (Glc6P), ATP and phosphoenolpyruvate (PPrv) in a flow-through reaction
      chamber. Appropriate conditions lead to the occurrence of (two) coexisting and
      markedly different time-independent states in the metabolite concentrations and
      fluxes. For particular experimental conditions, changes in the influx adenylic
      energy charge, [AEC]IN, may cause transitions between these alternative steady
      states which are either reversible as it occurs in classical hysteresis
      phenomena, or, more importantly, irreversible (irreversible transitions, IT)
      where the system is not able to switch back to its previous state even when the
      perturbation is reverted. The emergence of these irreversible transitions do not
      result from artificial or non-realistic experimental constraints, but are a
      potential intrinsic property of any non-linear dynamic system exhibiting bi- or
      multistability. These one-way transitions may well have important biological
      implications with respect to switching, adaptation and memory phenomena.

PMID- 9168983
TI  - Hydroxyl radical mediates N epsilon-(carboxymethyl)lysine formation from Amadori
      product.
AB  - Recent studies demonstrated N epsilon-(carboxymethyl)lysine (CML) in several
      tissue proteins. Incubation of proteins with glucose leads through a Schiff base
      to Amadori products. Oxidative cleavage of Amadori products is considered as a
      major route to CML formation in vivo, whereas it is not known which reactive
      oxygen species (ROS) is involved. The present study is undertaken to identify
      such a ROS. We prepared heavily glycated human serum albumin (HSA) which
      contained a high level of Amadori products, but an undetectable level of CML.
      Incubation of glycated HSA with FeCl2, but not with H2O2, led to CML formation
      which was enhanced by H2O2, but inhibited by catalase or mannitol, whereas
      superoxide dismutase had no effect. Similar data were obtained by experiments
      using Boc-fructose-lysine as a model Amadori compound. These data indicate that
      hydroxyl radical generated by the reaction of Fe2+ with H2O2 mediates CML
      formation from Amadori compounds.

PMID- 9168984
TI  - Functional expression and characterization of frog photoreceptor-specific calcium
      binding proteins.
AB  - S-modulin (sensitivity-modulating protein) is a photoreceptor-specific calcium
      binding protein which plays an important role in the light adaptation process by
      controlling rhodopsin phosphorylation in rods. S-modulin and its cone homologue,
      s26, were expressed at high level (more than 30% of total protein) in Escherichia
      coli and then purified. They both inhibited rhodopsin phosphorylation in a
      calcium dependent manner. Myristoylated recombinants of S-modulin and s26 showed
      calcium-dependent changes in tryptophan emission spectra with half-maxima at
      about 0.7 microM free calcium concentration. However, the spectral changes are
      distinctive from each other, suggesting that there is some difference in the
      structural change between S-modulin and s26.

PMID- 9168985
TI  - Scanning force microscopy of the interaction events between a single molecule of
      heavy meromyosin and actin.
AB  - How close an approach is necessary for two interactive protein molecules to
      recognize each other before association? How strong a force field is exerted
      between two proteins at the recognition distance? How extensive are the
      association interfaces? How strong a force is necessary to pull the associated
      proteins apart? By means of atomic force microscopy at a truly single molecule
      level, these fundamental and intriguing questions were answered with the muscle
      proteins actin and myosin.

PMID- 9168986
TI  - Membrane binding and enzymatic activation of a Dbl homology domain require the
      neighboring pleckstrin homology domain.
AB  - Dbl-homology (DH) domains are invariably located immediately N-terminal to a
      pleckstrin homology (PH) domain. To understand the functional relationship
      between these two domains we expressed the DH domain alone, the PH domain alone,
      and the DH-PH combination of the invasion inducing protein Tiam-1 fused to
      glutathione-S-transferase (GST) or green fluorescent protein (GFP). We found that
      the GST-DH-PH and the GST-PH constructs bind to preparations of brain membranes
      and to the beta gamma subunits of trimeric G proteins in vitro, while the GST-DH
      and GST control do not. The GFP-DH-PH and GFP-PH constructs are localized to
      peripheral membranes of COS-7 cells in vivo, while GFP and GFP-DH domain
      constructs are found diffusely in the cytoplasm. The DH-PH domain combination
      activates Jun N-terminal kinase (JNK) strongly, but the DH domain alone and the
      PH domain alone have little effect. We conclude that membrane localization and
      enzymatic activation of the DH domain require the adjacent PH domain.

PMID- 9168987
TI  - Molecular cloning and tissue expression of a novel orphan G protein-coupled
      receptor from rat lung.
AB  - G protein-coupled receptors transduce the signal of a wide variety of hormones,
      neurotransmitters, cytokines, and other molecules across the cell membrane to
      elicit the corresponding response inside the target cells. We describe in this
      paper the molecular cloning and tissue distribution of a novel rat G protein
      coupled receptor, GPR41, with highest homology to the human orphan G protein
      coupled receptor DRY12. A lower degree of homology was seen with the receptors
      for bradykinin, angiotensin, and IL8. The expression of GPR41 appears to be the
      highest in brain and lung tissues, with lesser expression in heart, skeletal
      muscle, and kidney, as assayed by northern blotting. No GPR41 message was seen in
      spleen, liver, or testes. GPR41 failed to bind any of the ligands tested.

PMID- 9168988
TI  - Binding of wild-type p53 by topoisomerase II and overexpression of topoisomerase
      II in human hepatocellular carcinoma.
AB  - In order to study the mechanisms by which p53 function is regulated, human wild
      type p53 cDNA was cloned into a vaccinia virus vector and the expressed p53
      protein was used to investigate binding of the p53 by cellular proteins from a
      cDNA expression library from human liver. One protein that bound wild-type p53
      had > 99% homology with DNA topoisomerase IIb. p53 protein was
      coimmunoprecipitated from topoisomerase II-rich cell lysates (but not from
      topoisomerase II-deficient cell lysates) by an antibody to topoisomerase IIa and
      IIb. This binding was shown to occur without a dsDNA intermediary. Hepatocellular
      carcinomas (HCCs) and adjacent nontumorous liver tissues from ten patients were
      studied to determine the level of expression of topoisomerase II and p53.
      Overexpressed topoisomerase II proteins were detected by western blot in six of
      ten HCCs (60%), including several in which presumed wild-type p53 was detected by
      immunohistochemistry. No topoisomerase II expression was detectable in the ten
      nontumorous liver tissues from the same patients or in a sample of normal human
      liver.

PMID- 9168989
TI  - A possible involvement of Stat5 in erythropoietin-induced hemoglobin synthesis.
AB  - Erythropoietin (EPO) and its cell surface receptor (EPOR) play central roles in
      the proliferation and differentiation of mammalian erythroid progenitor cells.
      Recently both the tyrosine residues in the EPOR responsible for the activation of
      Stat5 and the role of Stat5 for EPO-dependent cell proliferation have been shown.
      Here, we describe the roles of Stat5 and of these tyrosine residues in the EPOR
      in the erythroid differentiation of murine hematopoietic cell line SKT6 which
      produces hemoglobin in response to EPO. Chimeric receptors carrying the
      extracellular domain of the EGF receptor and the intracellular domain of the EPOR
      were introduced into SKT6 cells. Like EPO, EGF equally activated Stat5 and
      induced hemoglobin. Activation of Stat5 and hemoglobin expression by EGF were
      markedly impaired in cells expressing the tyrosine mutated chimeric receptors. In
      addition, ectopic expression of the prolactin receptor, another cytokine receptor
      that activates Stat5, led to hemoglobin synthesis. Finally, hemoglobin synthesis
      was severely inhibited by overexpressing a dominant negative form of Stat5. These
      results collectively suggest that Stat5 plays a role in EPO-mediated hemoglobin
      synthesis in SKT6 cells.

PMID- 9168990
TI  - Cloning of a mRNA preferentially expressed in chondrocytes by differential
      display-PCR from a human chondrocytic cell line that is identical with connective
      tissue growth factor (CTGF) mRNA.
AB  - Chondrocyte- or chondrosarcoma cell line (HCS)-specific DNA fragments were
      obtained using differential display-PCR. Nucleotide sequences of 32 species
      derived from HCS cells were determined. One of the sequence tags (tag no. 24)
      corresponded to the nucleotide sequence of connective tissue growth factor
      (CTGF). Northern blot analysis showed that CTGF was highly expressed in HCS cells
      and rabbit growth cartilage cells in culture but was not expressed in
      osteoblastic cells in culture. In situ hybridization revealed that CTGF was
      expressed only in the hypertrophic chondrocytes of costal cartilage and the
      vertebral column in embryonic mice. The expression of CTGF in HCS cells was up
      regulated by the addition of TGF-beta or BMP-2. These findings suggest that CTGF
      participates in endochondral ossification.

PMID- 9168991
TI  - Endogenous interleukin-1 receptor antagonist is neuroprotective.
AB  - Interleukin-1 (IL-1) has been implicated in chronic and acute cerebral
      neuropathologies. IL-1 receptor antagonist (IL-1ra), a naturally occurring
      protein that binds to IL-1 receptors without inducing signal transduction, blocks
      several actions of IL-1. IL-1ra acts at the local level and it also circulates in
      the bloodstream. We now report evidence for a biological function of IL-1ra in
      the brain as an endogenous neuroprotective molecule. Cerebral expression of IL
      1ra mRNA is induced rapidly by focal cerebral ischemia in rats, and inhibition of
      the action of IL-1ra, by passive immuno-neutralization, markedly enhances
      ischemic damage. To our knowledge this is the first report of an action of
      endogenous IL-1ra in the brain. Control of IL-1ra expression or action may
      therefore provide a useful therapeutic strategy to limit acute neurodegeneration.

PMID- 9168992
TI  - Differential expression of a proteasomal subunit during chick development.
AB  - Removal of cardiac neural crest disrupts normal development of the heart and
      pharynx. Subtractive hybridization was used to identify differentially expressed
      messages after neural crest ablation in chick embryos. A 1 kb clone, homologous
      to PROS-28, a 28 kD alpha subunit of a Drosophila proteasome, was differentially
      expressed in embryos lacking neural crest. An increase of GPROS-28 expression in
      the head and pharyngeal arches of stages 12-21 chick embryos without cardiac
      neural crest accompanied generalized low-level expression throughout experimental
      and normal embryos. In addition, high levels of GPROS-28 expression were detected
      in normal embryos at particular sites and times in development in the limb buds,
      mesonephros, heart, liver, neural tube, dorsal root ganglia, and lung buds, when
      the cells in these regions were undergoing intense proliferation.

PMID- 9168993
TI  - Nuclear and cytosolic calcium signaling induced by extracellular ATP in rat
      kidney inner medullary collecting duct cells.
AB  - Using a laser scanning confocal microscopy of fluorescent Ca2+ indicator (Fluo-3
      AM) the spatiotemporal Ca2+ dynamics in cultured kidney inner medullary
      collecting duct cells was investigated. In response to extracellular ATP (100
      microM), nuclear (Fln) and cytosolic (Flc) fluorescence intensity increased
      simultaneously. UTP similarly increased Fln and Flc, but ADP and AMP did not. A
      ratio between Fln and Flc was about 1.06 +/- 0.03 at rest and increased 1.71 +/-
      0.02 at the peak of stimulation (n = 74). In Ca(2+)-free condition, ATP increased
      Fln and Flc with a smaller peak intensity, but the peak ratio was similar (1.52
      +/- 0.03, n = 70). Faster time resolution of 100 ms in line scanning mode did not
      detect the delay between nuclear and cytosolic Ca2- responses. Our results
      indicate that nuclear Ca2+ was not diffused from the cytoplasm and that it may be
      directly released from the nuclear envelope, a possible Ca2+ store.

PMID- 9168994
TI  - Rat TAFII31 gene is induced upon programmed cell death in differentiated PC12
      cells deprived of NGF.
AB  - Typical programmed cell death (PCD) requires de novo macromolecular synthesis and
      shares common morphological changes referred to as apoptosis. To elucidate the
      molecular mechanism of apoptosis, we isolated cDNA clones that are induced in
      differentiated PC12 cells deprived of NGF by differential display method. Among
      such clones, homology searches revealed that the one clone encodes the rat TATA
      binding-protein-associated factor TAFII31, a component of TFIID, and a
      transcriptional coactivator of the p53 protein. Northern analysis of various
      organs in human showed one band in heart, brain, skeletal muscle and pancreas,
      whose size is approximately 1.1 kb which identical to that of human TAFII31 mRNA,
      although the size of rat human TAFII31 mRNA is approximately 2.7 kb. The deduced
      amino acid sequence of the rat TAFII31 was 77% identical to that of the human
      TAFII31. Northern analysis of various organs in adult mice showed that expression
      levels of TAFII31 mRNA were strong in heart but weak in spleen, although this
      gene is ubiquitously expressed.

PMID- 9168995
TI  - Antisense oligonucleotides discriminating between two muscular Na+ channel
      isoforms.
AB  - Various 15-mer antisense oligodeoxynucleotides (aODNs) were constructed against
      RNAs coding for two closely related isoforms of the voltage-dependent Na+
      channel, i.e. those of human heart (hH1) and skeletal (hSkM1) muscle. When
      translated in vitro, either RNA yielded a 220 kDa band on polyacrylamide gels,
      indicating that the translation product had full length. Of six different aODN
      constructs developed against hH1 RNA, two each inhibited translation completely,
      moderately or not at all, depending on the target position. The specificity of
      the effect (no cross reaction at 10 microM) was confirmed by incubation with 15
      mer aODNs against hSkM1 RNA. The most effective aODNs were those hybridizing
      between bases 3840 and 3880 of hSkM1 RNA and the homologous segment of hH1 RNA.
      When either of the RNAs was co-injected with its most effective (phospho
      rothioate-capped) aODN into Xenopus oocytes, the production of Na+ channels was
      strongly suppressed (relative INa for hSkM1: 0.08 +/- 0.05 times control, n = 14;
      for hH1: 0.11 +/- 0.08, n = 11). We conclude that aODNs are able to discriminate
      between closely related RNAs. The efficacy of an aODN depends strongly on its RNA
      target position.

PMID- 9168996
TI  - Osteogenic protein-1 mRNA in the uterine endometrium.
AB  - OP-1, a bone morphogenetic protein (BMP) in the TGF-beta superfamily, is
      expressed at high levels in the kidney and in the endometrium of the uterus of
      non-pregnant mice. During pregnancy the OP-1 mRNA in the endometrium rapidly
      declined at 4 dpc. Thereafter, OP-1 transcripts were detected in the
      trophoblastic giant cells of the placenta and the fetal tissues. The uterine OP-1
      mRNA downregulation could be mimicked by administration of 17 beta-estradiol but
      not by progesterone to non-pregnant animals. In contrast, OP-1 mRNA expression in
      kidneys and ovaries was not affected by pregnancy or estrogen treatment. The
      selective effect of estrogen on OP-1 mRNA in the uterus suggests that OP-1
      expression is regulated by tissue specific mechanisms.

PMID- 9168997
TI  - Changes in BRCA2 expression during progression of the cell cycle.
AB  - It has been shown that genetic alterations in BRCA1 and BRCA2 can predispose an
      individual to develop breast cancer. We investigated the expression of both BRCA2
      and BRCA1 during the progression of the cell cycle by northern blot analysis. In
      MCF-10F (normal breast epithelial cell line) and MCF-7 (breast cancer cell line)
      cells the expression of BRCA2 RNA was low in G0 and early G1 phases then up
      regulated at the G1/S phase junction. Expression of BRCA2 was maintained at
      relatively high levels when cells progressed through S and G2/M phases. For MCF-7
      cells, the level of BRCA2 transcript decreased as cells were released from
      nocodazole-mediated metaphase arrest. This is consistent with the observation of
      low but detectable BRCA2 RNA level in G1 phase of the cell cycle. For both cell
      lines, the patterns of RNA expression of BRCA1 and BRCA2 were similar during the
      proliferation phase of cell cycle. However, the transcripts from both genes were
      undetectable in quiescent cells. These results suggest important functions for
      both BRCA2 and BRCA1 in regulation of cell growth.

PMID- 9168998
TI  - Sarcoplasmic reticulum-associated and protein kinase C-regulated ADP-ribosyl
      cyclase in cardiac muscle.
AB  - Two types of ADP-ribosyl cyclase activity were distinguished in dog and rat
      cardiac muscles by measuring the enzymatic conversion of NGD (as an NAD analog)
      into the fluorescent product cyclic GDP-ribose in cardiac muscle subcellular
      fractions. Both types of activity were confined to membrane fractions isolated
      from microsomes by sucrose gradient centrifugation. One of the activities co
      purified with fractions that were enriched in sarcolemma (SLM), as evidenced by
      immunodetection of the dihydropyridine receptor, while the other activity was
      found to co-precipitate with the sarcoplasmic reticulum (SR), that was identified
      on the basis of its immuno-staining with a ryanodine receptor monoclonal
      antibody. In certain aspects, the plasma membrane-bound ADP-ribosyl cyclase
      activity resembled the characteristics of CD38 or CD38-like proteins: it was
      sensitive to thiols and lectins and was recognized by a monoclonal anti CD38
      antibody. The SR enzyme had apparently distinct properties, as it was insensitive
      to both thiols and lectins and was not recognized by the CD38 antibody. In
      addition, the SR-associated ADP-ribosyl cyclase was inhibited by endogenous
      protein kinase C (PKC)-dependent phosphorylation in both dog and rat cardiac SR.
      The PKC-modulated SR ADP-ribosyl cyclase we describe here might be a principal
      component of the signal transduction machinery that is responsible for regulation
      of the intracellular levels of cADPR.

PMID- 9168999
TI  - Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c.
AB  - SNARE proteins have been implicated in the insulin-induced translocation of
      vesicles containing the GLUT4 glucose transporter to the plasma membrane of
      adipocytes. The role of the target SNARE SNAP-25 or its homologs in this process
      was investigated by screening a mouse adipocyte cDNA library with rat SNAP-25 and
      human SNAP-23 cDNA probes. Both positive clones isolated encoded a protein with
      87% sequence identity to human SNAP-23, and which was therefore designated mouse
      SNAP-23. Immunoblot and immunofluorescence analyses revealed that SNAP-23 is
      located predominantly in the plasma membrane of 3T3-L1 adipocytes incubated in
      the absence or presence of insulin. Of syntaxins 1 to 5, SNAP-23 bound with the
      highest affinity to syntaxins 1 and 4 in the yeast two-hybrid system. Expression
      of SNAP-23, syntaxin 4, and the syntaxin-binding protein Munc 18c in COS cells
      revealed that Munc18c reduced the amount of SNAP-23 bound to syntaxin 4 in a
      concentration-dependent manner. These results suggest that the binding of SNAP-23
      to syntaxin 4 is inhibited by Munc18c in adipocytes.

PMID- 9169000
TI  - Effect of boric acid solution on cartilage metabolism.
AB  - Pelvic cartilage of chick embryo was used to demonstrate that presence of boron
      in culture medium decreases synthesis of proteoglycans, collagen and total
      proteins but on the other hand increases the release of these macromolecules.
      However, when glucose concentration in culture medium is brought to 22mM, the
      synthesis decrease is no longer observed, whereas release increase persists.
      Proteins released into the culture medium included heat shock proteins (70 hsp)
      and tumor necrosis factor alpha (TNF alpha). The amount of phosphorylated
      proteins was enhanced in presence of boron while endoprotease activity in
      cartilage and in culture medium was significantly augmented. The in vitro effects
      of boric acid may explain its in vivo effect on wound healing.

PMID- 9169001
TI  - Electrolyzed-reduced water scavenges active oxygen species and protects DNA from
      oxidative damage.
AB  - Active oxygen species or free radicals are considered to cause extensive
      oxidative damage to biological macromolecules, which brings about a variety of
      diseases as well as aging. The ideal scavenger for active oxygen should be
      'active hydrogen'. 'Active hydrogen' can be produced in reduced water near the
      cathode during electrolysis of water. Reduced water exhibits high pH, low
      dissolved oxygen (DO), extremely high dissolved molecular hydrogen (DH), and
      extremely negative redox potential (RP) values. Strongly electrolyzed-reduced
      water, as well as ascorbic acid, (+)-catechin and tannic acid, completely
      scavenged O.-2 produced by the hypoxanthine-xanthine oxidase (HX-XOD) system in
      sodium phosphate buffer (pH 7.0). The superoxide dismutase (SOD)-like activity of
      reduced water is stable at 4 degrees C for over a month and was not lost even
      after neutralization, repeated freezing and melting, deflation with sonication,
      vigorous mixing, boiling, repeated filtration, or closed autoclaving, but was
      lost by opened autoclaving or by closed autoclaving in the presence of tungsten
      trioxide which efficiently adsorbs active atomic hydrogen. Water bubbled with
      hydrogen gas exhibited low DO, extremely high DH and extremely low RP values, as
      does reduced water, but it has no SOD-like activity. These results suggest that
      the SOD-like activity of reduced water is not due to the dissolved molecular
      hydrogen but due to the dissolved atomic hydrogen (active hydrogen). Although SOD
      accumulated H2O2 when added to the HX-XOD system, reduced water decreased the
      amount of H2O2 produced by XOD. Reduced water, as well as catalase and ascorbic
      acid, could directly scavenge H2O2. Reduce water suppresses single-strand
      breakage of DNA b active oxygen species produced by the Cu(II)-catalyzed
      oxidation of ascorbic acid in a dose-dependent manner, suggesting that reduced
      water can scavenge not only O2.- and H2O2, but also 1O2 and .OH.

PMID- 9169002
TI  - Diverse cytoprotectants prevent cell lysis and promote recovery of respiration
      and ion transport.
AB  - Numerous agents have been reported to prevent cell lysis. However, little
      information is available concerning the ability of cytoprotectants to promote the
      return of physiological functions. The goal of this study was to determine
      whether a diverse group of cytoprotectants prevent cell lysis and promote the
      recovery of respiration and ion transport following anoxia (60 min)/reoxygenation
      (60 min) in rabbit renal proximal tubule (RPT) suspensions. Cell lysis (LDH
      release) was determined immediately following the anoxic and reoxygenation
      periods. Mitochondrial function (basal respiration) and active Na+ transport
      (ouabain-sensitive respiration) was determined after the reoxygenation period.
      LDH release increased to 75 +/- 11% after the anoxic period and did not increase
      further during the reoxygenation period. LDH release in controls was 6 +/- 1% and
      did not vary over time. Glycine (2 mM), strychnine (1 mM), nifedipine (100
      microM) and niflumic acid (100 microM) added immediately prior to the anoxic
      period completely blocked LDH release. All cytoprotectants increased basal
      respiration from 39 +/- 7% of controls in the anoxic samples to 65-77% of
      controls. Glycine, strychnine and nifedipine increased ouabain-sensitive
      respiration from 10 +/- 3% of controls in anoxic samples to 51-77% of control.
      Niflumic acid did not increase ouabain-sensitive respiration. These results
      demonstrate that glycine, strychnine and nifedipine are "true' cytoprotectants
      preventing both cell lysis and promoting the recovery of mitochondrial function
      and ion transport after an anoxic insult.

PMID- 9169003
TI  - Expression of co-factors (SMRT and Trip-1) for retinoic acid receptors in human
      neuroectodermal cell lines.
AB  - Retinoic acid (RA) induces growth inhibition, differentiation or cell death in
      many human neuroblastoma cell lines. Recently, the transactivation activity of
      nuclear retinoids receptors has been shown to be modulated through physical
      association with other proteins that act as co-activators or as co-repressors. We
      investigated the expression of the co-repressor (SMRT) and co-activator (Trip 1)
      for retinoid and thyroid-hormone receptors in several neuroectodermal tumour cell
      lines, and its modulation by all-trans-retinoic acid, as well as by synthetic
      agonists, for RAR alpha, RAR beta, RAR gamma and RXR. We demonstrate that (i)
      SMRT and Trip-1 mRNAs are expressed in many human neuroblastoma and melanoma cell
      lines in basal conditions, (ii) SMRT mRNA expression in human neuroblastoma cell
      line SK-N-BE(2) increases after 48 hours of incubation with 1 microM RA and RARs
      specific agonists, (iii) Trip-1 mRNA in the same cell line does not change during
      incubation with RA or selective synthetic agonists for RARs and RXR.

PMID- 9169004
TI  - Expression of the Solfolobus acidocaldarius Rieske iron sulfur protein II (SOXF)
      with the correctly inserted [2FE-2S] cluster in Escherichia coli.
AB  - The Rieske protein II (Schmidt et al., 1996, FEBS Lett. 388, 43-46) from the
      thermoacidophilic crenarcheon Sulfolobus acidocaldarius (DSM 639) was expressed
      in E. coli cells. The full length protein was strictly bound to the E. coli
      membranes and could only be removed by detergent treatment indicating the
      presence of a membrane anchor. The iron sulfur cluster was correctly inserted
      into a fraction of the full length protein and much more effectively into a
      soluble form created by the deletion of the 45 N-terminal amino acids. The
      soluble form of the protein displayed the typical spectroscopic properties of a
      respiratory Rieske protein. The midpoint potential was +375 mV determined by CD
      redox potentiometry. The presented data demonstrate that the structure of the
      recombinant protein is very similar or identical to the authentic protein making
      this a powerful model system for the studies of Rieske proteins by site directed
      mutagenesis.

PMID- 9169005
TI  - Purification and characterization of a phytase from Klebsiella terrigena.
AB  - A cytoplasmatic phytase was purified about 410-fold to apparent homogeneity with
      a recovery of 28%. The enzyme is induceable under carbon limitation in the
      presence of phytate. It behaves as a monomeric protein of a molecular mass of
      about 40 kDa. The phytase is rather specific for phytate and exhibits optimal
      conditions for phytate degradation at pH 5.0 and 58 degrees C. Kinetic parameters
      for the hydrolysis of Na phytate are KM 300 microM and kcat 180 s-1 at 35 degrees
      C and pH 5.0. Phytate is hydrolyzed in a stepwise manner; the penta- and
      tetrakisphosphate were identified as I(1,2,4,5,6)P5 and I(1,2,5,6)P4.
      Consequently, this enzyme is a 3-phytase (EC 3.1.3.8).

PMID- 9169006
TI  - The regio- and stereo-selectivity of C19 and C21 hydroxysteroid glucuronidation
      by UGT2B7 and UGT2B11.
AB  - The capacity of two human hepatic UDP-glucuronosyltransferase (UGT) isoforms,
      UGT2B7 and UGT2B11, to metabolize more than 50 hydroxylated androgens and
      pregnanes was investigated. All mono- and dihydroxylated androgens with a
      hydroxyl function in the 3 alpha, 6 alpha, and 17 beta positions were
      glucuronidated by UGT2B7, but highest activity was generally observed for
      steroids containing a 3 alpha-hydroxy substituent. UGT2B7 did not glucuronidate 2
      alpha-, 2 beta-, 3 beta-, 6 beta-, 7 alpha-, 11 alpha-, and 11 beta
      monohydroxylated androgens, although the presence of hydroxyl groups at certain
      of these positions did not abolish the ability of UGT2B7 to metabolize diols
      which also possessed a 3 alpha- or 17 beta-hydroxyl group. 3 alpha
      Hydroxypregnanes were also glucuronidated by UGT2B7. Activity was not detected
      for 6 alpha-, 6 beta-, 11 beta-, 12 alpha-, 16 alpha-, 17 alpha-, 20 alpha-, or
      21-monohydroxylated pregnanes. Although 11 alpha-hydroxylated androgens were not
      glucuronidated by UGT2B7, this enzyme exhibited high activity toward the 11 alpha
      hydroxylated derivatives of 5 beta-prenanedione and progesterone. UGT2B11
      similarly glucuronidated 3 alpha-hydroxyandrogens and -pregnanes, but rates of
      metabolism were low compared to UGT2B7. With the exception of androsterone and
      its 5 beta-isomer, ring A/B stereochemistry appeared not to influence rates of
      hydroxysteroid glucuronidation by UGT2B7 and UGT2B11. Overall, the data indicate
      a high degree of stereo- and regioselectivity in the glucuronidation of
      hydroxyandrogens and -pregnanes by UGT2B7 and UGT2B11 and further suggest that
      UGT2B7 may contribute to the glucuronidation of 3 alpha-hydroxysteroids in
      humans.

PMID- 9169007
TI  - Effect of individual carbohydrate chains of recombinant antithrombin on heparin
      affinity and on the generation of glycoforms differing in heparin affinity.
AB  - Two major glycoforms of recombinant antithrombin which differ 10-fold in their
      affinity for the effector glycosaminoglycan, heparin, were previously shown to be
      expressed in BHK or CHO mammalian cell lines (I. Bjork, et al., 1992, Biochem. J.
      286, 793-800; B. Fan et al., 1993, J. Biol. Chem. 268, 17588-17596). To determine
      the source of the glycosylation heterogeneity responsible for these different
      heparin-affinity forms, each of the four Asn residue sites of glycosylation,
      residues 96, 135, 155, and 192, was mutated to Gln to block glycosylation at
      these sites. Heparin-agarose chromatography of the four antithrombin variants
      revealed that Gln 96, Gln 135, and Gln 192 variants still displayed the two
      functional heparin-affinity forms previously observed with the wild-type
      inhibitor, whereas the Gln 155 variant showed only a single functional high
      heparin affinity form. These results demonstrate that heterogeneous glycosylation
      of Asn 155 of recombinant antithrombin is responsible for generating the low
      heparin affinity glycoform. Analysis of heparin binding to the higher heparin
      affinity forms of the four variants showed that all exhibited increased heparin
      affinities of two- to sevenfold compared to wild-type higher heparin affinity
      form or to plasma antithrombin, with the Gln 135 variant showing the largest
      effect on this affinity. The extent of heparin-affinity enhancement was
      correlated with the distance of the mutated glycosylation site to the putative
      heparin-binding site in the X-ray structure of antithrombin. All variants
      displayed normal kinetics of thrombin inhibition in the absence and presence of
      saturating heparin, indicating that the carbohydrate chains solely affected
      heparin binding and not heparin-activation or proteinase-binding functions. These
      results indicate that all carbohydrate chains of recombinant antithrombin
      adversely affect heparin-binding affinity to an extent that correlates with their
      relative proximity to the putative heparin-binding site in antithrombin.

PMID- 9169008
TI  - Characterization of linamarase of latex and its localization in petioles in
      cassava.
AB  - The distribution of linamarase in latex and its purification, characterization,
      and immunocytochemical localization in petioles were studied in order to get an
      insight into the process of cyanogenesis in cassava. Crude latex exudate
      exhibited low linamarase activity, but on dilution the activity increased about
      fivefold. Assay using petiole latex collected in isotonic medium showed that the
      enzyme was distributed in vesicle-like structures. In vitro studies showed that
      about 50% activity was released from the vesicle into the medium within an hour.
      Latex linamarase was purified by ammonium sulfate fractionation and DEAE
      cellulose chromatography and was characterized with respect to its amino acid
      composition and kinetic properties. Gel filtration and SDS-PAGE analysis showed
      that the enzyme was made up of a 70,000-Da peptide. Immunocytochemical studies on
      the localization of linamarase in cassava petioles showed sporadic positive
      staining in the phloem and intense staining in the thickened corners of the
      collenchyma cells of the cortex, suggesting the distribution of linamarase in
      laticifers as well as in the cell wall.

PMID- 9169009
TI  - Epitope mapping of cytochrome P450cam (CYP101).
AB  - Eighteen linear antigenically active sites were revealed in cytochrome P450 from
      Pseudomonas putida (P450cam) by hexapeptide scanning. These sites occupy about
      31% of the protein sequence. Hexapeptide epitope sequences of P450cam are not
      found in other cytochromes P450. However, several cytochromes P450 contain
      shorter fragments of P450cam epitope sequences which may cause weak immune cross
      reactions. P450cam antigenic determinants are located generally at the boundaries
      of secondary structure elements. Mapping of P450cam antigenic determinants on the
      three-dimensional structure of this protein reveals 14 highly water-accessible
      antigenic sites and only 1 site (No. 322-327, QMLSGL) which is inaccessible to
      water. Several functionally important sites and amino acid residues of P450cam
      are localized within revealed linear epitopes or very close to them. These sites
      include substrate-binding regions, residues responsible for the putidaredoxin
      interaction (Arg72, Arg112, Lys314, and Arg364), heme binding (Gln108, Arg112,
      Asp297, Arg299, and Cys357), and proton translocation (Lys178, Arg186, and
      Glu366).

PMID- 9169010
TI  - Docking of verapamil in a synthetic Ca2+ channel: formation of a ternary complex
      involving Ca2+ ions.
AB  - The mechanism by which diverse drugs modulate voltage-dependent Ca2+ channels is
      ill-understood. We have approached this problem by examining the interaction of
      verapamil with a 97-residue synthetic channel peptide (SCP) that exhibits
      functional similarities to authentic L-type Ca2+ channels in terms of cation
      selectivity and permeation as well as interaction with channel-activating and
      blocking drugs (Grove et al. (1991) Proc. Natl. Acad. Sci. USA 88, 6418).
      Different possibilities of binding of verapamil inside the Ca(2+)-bound SCP were
      simulated using the Monte Carlo-with-energy-minimization method. In the optimal
      mode of the binding, verapamil adopted a folded conformation and fit snugly in
      the pore. The dimethoxyphenyl groups of the drug interacted with two Ca2+ ions
      coordinated to the acidic residues of SCP, thus forming a ternary complex of the
      drug, Ca2+, and channel. The isopropyl group of verapamil abetted a ring of four
      Ile residues constituting the putative SCP gate. The occlusion of this gate by
      verapamil in this manner was strikingly similar to that accomplished by the
      methyl group of dihydropyridine drugs. In conjunction with an earlier study on
      SCP bound to dihydropyridine drugs (Zhorov and Ananthanarayanan (1996) Biophys.
      J. 70, 22), our data suggest that, in general, drug modulation of SCP would
      involve the interaction of the ligands with the pore-bound Ca2+ and with the
      hydrophobic gate. In light of the functional similarity between SCP and L-type
      Ca2+ channel, it is likely that the latter would also interact with drugs in a
      similar fashion.

PMID- 9169011
TI  - Degradation of hyaluronan by peroxynitrite.
AB  - Treatment of high-molecular-weight hyaluronan (HA) with peroxynitrite at neutral
      pH (ONOO-/ONOOH) results in altered mobility on agarose gel electrophoresis, as
      well as reduced limiting viscosity number. Both effects are consistent with a
      reduction in HA molecular weight. HA is protected from peroxynitrite attack to
      varying extents by addition of alternate target molecules. Thiourea is extremely
      effective as a protective agent, dimethyl sulfoxide is moderately effective,
      while sodium benzoate and mannitol are slightly effective. A similar pattern of
      protection is observed when HA is degraded by hydroxyl radical generated by a
      metal ion/hydrogen peroxide system. On the basis of these observations,
      peroxynitrite is proposed to have hydroxyl radical-like activity in degrading HA.

PMID- 9169012
TI  - Ozone does not react with human erythrocyte membrane lipids.
AB  - Ozone was applied to sealed red cell ghost membranes at the rate of 95 nmol/min
      for periods up to 20 min. Acetylcholine esterase, on the outer face of the
      membrane, was inhibited up to 20%. Glyceraldehyde-3-phosphate dehydrogenase, on
      the inner surface of the membrane, was inhibited up to 87%. These differences
      reflected the inherent susceptibilities of the two enzymes and the presence or
      absence of the membrane barrier. Analysis of the total lipids of the ozone
      treated ghosts showed no significant change in the distribution of lipid classes
      and no significant change in the fatty acid composition. There was no significant
      change in the fatty acid composition of the phosphatidylcholine fraction. There
      was a slight increase in 18:0 and 20:2 + 20:3 in the phosphatidylethanolamine
      fraction. There was no change in the molecular species distribution of the
      phosphatidylcholine or the phosphatidylethanolamine fraction. There was no
      evidence for the formation of the phospholipid ozonolysis product, 1-acyl-2-(9
      oxo-nonanyl) derivatives of glyceryl-phosphoryl choline. There was no decline in
      the amount of cholesterol in the lipids derived from ozone-treated red cell
      membranes. Treatment of red cell ghost membranes and, by implication, the plasma
      membrane of cells by ozone therefore oxidizes peripheral proteins before it
      oxidizes lipids.

PMID- 9169013
TI  - Evidence that protein kinase C is involved in delta-aminolevulinate synthase
      expression in rat hepatocytes.
AB  - There are many factors that regulate the rate of synthesis of delta
      aminolevulinate synthase (ALA-S), the enzyme which governs the rate-limiting step
      in heme biosynthesis. In rat hepatocytes, phenobarbital increases ALA-S gene
      transcription and dibutyryl cAMP potentiates this induction, whereas insulin and
      glucose have the opposite effect. The present report provides evidence that
      protein kinase C (PKC) activation negatively influences ALA-S mRNA levels, as
      measured by Northern and slot-blot analysis. The addition of 1,2-dioctanoyl-sn
      glycerol (DOG) or 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC activator
      that mimics diacylglycerol function, to cultures led to a significant decrease of
      both basal and phenobarbital-induced ALA-S mRNA levels in a dose-dependent
      manner. This TPA effect depends on the specific activation of PKC because the
      analog 4 alpha-phorbol 12,13-diacetate, a nonstimulatory PKC phorbol ester, is
      unable to inhibit ALA-S mRNA. Furthermore, the effect of TPA is blocked by the
      PKC inhibitors staurosporine and calphostin C. Desensitization of the PKC pathway
      by prolonged exposure to TPA abolished the subsequent action of the phorbol
      ester. On the other hand, neither TPA nor DOG modified the half-life of ALA-S
      mRNA. The study of the combinatorial action of TPA and cAMP revealed that the
      inhibitory effect of TPA overcomes dibutyryl cAMP induction. Thus, these results
      indicate that PKC plays an essential role in regulating ALA-S expression,
      probably at a transcriptional level.

PMID- 9169014
TI  - Identification of proteolipid from an extremely halophilic archaeon Halobacterium
      salinarum as an N,N'-dicyclohexyl-carbodiimide binding subunit of ATP synthase.
AB  - ATP synthesis in an extremely halophilic archaeon, Halobacterium salinarum, was
      inhibited by N-cyclohexyl-N'-[4-(dimethylamino)-alpha-naphthyl]carbodiimide (NCD
      4), a fluorescent analog of N,N'-dicyclohexylcarbodiimide (DCCD). By tracing the
      fluorescent signal, a hydrophobic 8-kDa protein (proteolipid) was purified from
      the halobacterial membrane as one of the most DCCD-reactive proteins and its N
      terminal amino acid sequence was determined. The gene encoding the proteolipid
      was found in the region upstream of the genes encoding the two major subunits of
      halobacterial A-type ATPase [K. Ihara and Y.Mukohata (1991) Arch. Biochem.
      Biophys. 286, 111-116]. Halobacterial proteolipid was more similar in size to the
      proteolipid of F-type ATPase than that of V-type ATPase. However, multiple amino
      acid sequence alignment of proteolipids showed a higher degree of relatedness
      between V-type and A-type ATPase proteolipids. Together with the recent finding
      of a triplicate proteolipid encoding gene from the methanogenic archaeon
      Methanococcus jannaschii [C. J. Bult et al. (1996) Science 273, 1058-1073],
      proteolipids from archaea seem to have diverse characteristics in comparison with
      those from eubacteria or from eukaryotes.

PMID- 9169015
TI  - Identification of critical positive charges in XIP, the Na/Ca exchange inhibitory
      peptide.
AB  - The peptides XIP (RRLLFYKYVYKRYRAGKQRG) and C28R2 (LRRGQILWFRGLNRIQTQIRVVKAFRSS)
      correspond to the autoinhibitory domains of the Na-Ca exchanger and the plasma
      membrane Ca pump, respectively. An increase of ionic strength reduced the
      inhibition of exchange activity by XIP and C28R2, consistent with an important
      role for electrostatic interactions. Sulfosuccinimidyl acetate (SNA)-modified XIP
      did not inhibit Na-Ca exchange. Because SNA modifies lysines, we conclude that at
      least one of the positive charges at the XIP lysine positions (7, 11, or 17) is
      important for inhibition. 2CK-XIP (RRLLFYRYVYRCYCAGRQKG) has cysteines at 12 and
      14 and only one lysine (at 19).2CK-XIP inhibited Na-Ca exchange; thus positive
      charges at 12 and 14 are not essential. SNA-modified 2CK-XIP did not inhibit;
      thus a positive charge at 19 is important. Iodoacetic acid-modified 2CK-XIP
      inhibits the Na-Ca exchanger but not the PM Ca pump. These results show that the
      structural determinants for inhibition of the Na-Ca exchanger and the PM Ca pump
      are different, that positive charges at 7, 11, or 17 (or some combination) are
      more important than positive charges at 12 and 14 for inhibition by XIP of the Na
      Ca exchanger.

PMID- 9169016
TI  - Loading of iron into recombinant rat liver ferritin heteropolymers by
      ceruloplasmin.
AB  - We have reported previously that the heavy chain of ferritin is required for iron
      incorporation by ceruloplasmin (J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch.
      Biochem. Biophys. 335(1)). The purpose of this study was to determine how many
      heavy chains were required for ceruloplasmin to interact with ferritin such that
      iron loading occurred. The cDNA sequences encoding the heavy and light chains of
      rat liver ferritin were cloned into the baculovirus transfer vector pA-cUW51
      under the control of polyhedrin and p10 promoters, respectively, which was then
      incorporated by homologous recombination into the infections Autographa
      californica nuclear polyhedrosis virus genome. Both ferritin chains were
      expressed and assembled into two heteropolymers following the infection of insect
      cells by recombinant virus, which were separated by DEAE-Sepharose
      chromatography. The percentage of heavy (H) and light (L) chains making up the
      two heteropolymers, determined by gel scanning following the resolution of chains
      on SDS-PAGE, were equivalent to 1 H and 23 L chains and 2 H and 22 L chains. The
      maximal extent of iron loading was observed using 1 mol of rat ceruloplasmin per
      mole of H chain in the two heteropolymers. The extent of iron incorporation
      decreased with additional ceruloplasmin. Iron incorporation into rat liver
      ferritin, found to contain 10 H chains, increased as the molar ratio of
      ceruloplasmin to ferritin increased to 4:1 and remained the same up to 8:1. Iron
      loading into horse spleen ferritin, found to have one H chain, appeared similar
      to that for recombinant ferritin, having only one H chain. Therefore, we propose
      that the optimal molar ratio of ceruloplasmin to ferritin depends upon the
      numbers of H chain making up the ferritin molecule for the maximal incorporation
      of iron into ferritin. These results also suggest that the iron loading channel
      is contained within a single H chain subunit.

PMID- 9169017
TI  - The mechanism of apolipoprotein B-100 thiol depletion during oxidative
      modification of low-density lipoprotein.
AB  - Oxidation of low-density lipoprotein (LDL) is recognized to be a key step in
      atherogenesis. Previous studies show that LDL contains low-molecular-weight
      antioxidants such as vitamin E, beta-carotene, and ubiquinol, which can retard
      oxidative modification. In this report, we have evaluated the antioxidant
      potential of apolipoprotein B-100 (apo-B) thiols during LDL oxidation. Both apo-B
      thiols and vitamin E were depleted concomitantly during the lag phase of Cu(2+)
      mediated LDL oxidation. The rate of thiol depletion was significantly inhibited
      by the lipophilic spin trap N-tert-butyl-alpha-phenylnitrone (PBN) but not by the
      water-soluble spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN).
      Blocking apo-B thiols with sulfhydryl modifying agents increased the
      oxidizability of LDL. As with Cu2+, peroxynitrite also caused depletion of apo-B
      thiols, and again thiol depletion was inhibited by PBN but not by POBN. A
      PBN/lipid-derived radical adduct was observed by the electron spin resonance
      technique during oxidation of LDL with peroxynitrite. We conclude that apo-B
      thiol depletion is mediated by lipid peroxidation, prior to the onset of the
      propagation phase of LDL oxidation. The implications of apo-B thiols an intrinsic
      antioxidants of LDL are discussed.

PMID- 9169018
TI  - Rapid kinetic studies of SH oxidation-induced calcium release from sarcoplasmic
      reticulum vesicles.
AB  - We studied the kinetics of calcium release induced by SH oxidation in triads
      isolated from frog and rabbit skeletal muscle by measuring calcium fluxes by a
      fast filtration method. In both species SH oxidation induced release of 70-80% of
      the passively loaded calcium with a rate constant of 1 s-1. This rate constant is
      3 times higher than the rate constant of calcium-induced calcium release and 15
      times lower than the rate constant of ATP-induced release. Calcium release
      induced by SH oxidation exhibited the same calcium dependence of calcium-induced
      calcium release and was also inhibited by physiological [MG2+]. Neither SH
      oxidation-induced calcium release nor calcium-induced calcium release were
      regulated by luminal calcium. The redox state of thiol groups does not seem to
      control ATP-induced calcium release since the rate constant of calcium release
      after SH oxidation was not different from the rate constant measured in the
      presence of the reducing agent dithiothreitol. Our results do not support a role
      for SH oxidation, per se, as an essential step for the release of calcium from
      sarcoplasmic reticulum.

PMID- 9169019
TI  - DNA damage, gadd153 expression, and cytotoxicity in plateau-phase renal proximal
      tubular epithelial cells treated with a quinol thioether.
AB  - 2-Bromo-bis-(glutathion-S-yl)hydroquinone [2-Br-bis-(GSyl)HQ] causes DNA single
      strand breaks (SSB), causes growth arrest, induces the expression of gadd153 (a
      gene inducible by growth arrest and DNA damage), and decreases histone H2B mRNA
      in log-phase renal proximal tubular epithelial cells (LLC-PK1). Renal epithelial
      cells in vivo normally exhibit a low mitotic index, therefore experiments in both
      plateau- and log-phase cells are necessary for a comprehensive understanding of
      the stress response to 2-Br-bis-(GSyl)HQ. In the present article we demonstrate
      that not all features of the stress response in log-phase cells are reproduced in
      plateau-phase cells. Thus, although 2-Br-bis-(GSyl)HQ causes concentration and
      time-dependent increases in DNA SSB, and increases the expression of gadd153,
      histone H2B mRNA levels are unaltered in plateau-phase cells. The relationship
      between reactive oxygen species, DNA damage, gene expression, and cytotoxicity
      was also investigated. Our findings suggest that (i) 2-Br-bis-(GSyl)HQ-mediated
      DNA damage in LLC-PK1 cells is mediated by the generation of H2O2; (ii) DNA
      damage, either directly or indirectly, contributes to cell death; and (iii) DNA
      damage, either directly or indirectly, provides the initial signal for gadd153
      expression. In addition, DNA repair is rapid in LLC-PK1 cells, and the DNA-repair
      inhibitors 1-beta-D-arabinofuranosylcytosine and hydroxyurea have no effect on
      the amount of DNA SSB. Although the addition of 3-aminobenzamide following 2-Br
      bis-(GSyl)HQ exposure has no effect on the removal of DNA SSB, it causes a slight
      but significant increase in gadd153 expression and cell viability, indicating
      that activation of poly(ADP-ribose)polymerase may exacerbate toxicity. Finally,
      aurintricarboxylic acid did not prevent DNA SSB or cytotoxicity in 2-Br-bis
      (GSyl) HQ-treated LLC-PK1 cells, implying that activation of endonucleases does
      not play a role in these processes.

PMID- 9169020
TI  - Construction and expression of chimeric rat liver hydroxysteroid sulfotransferase
      isozymes.
AB  - The St-20 and ST-40 cDNAs encode rat liver hydroxysteroid sulfotransferases (HS
      ST) that are 90% identical in amino acid sequence but exhibit different substrate
      preferences for dehydroepiandrosterone (DHEA), androsterone (AD), and cortisol
      (CS). ST-40 is active for all three substrates, whereas ST-20 is mainly active
      for cortisol. To determine the domain responsible for the substrate preferences
      of the HS-STs, 20 chimeric HS-STs were constructed by reciprocal exchanges of DNA
      fragments derived from the cDNAs and were expressed in Escherichia coli. Some
      chimeric enzymes were enzymatically active for all three substrates, and some
      displayed reduced or lost CS-ST activity, with retention of DHEA- and AD-ST
      activities. Others lost all HS-ST activity. Analysis revealed that a central
      region (region III spanning amino acids 102-164 with five amino acid differences
      between ST-20 and ST-40) is essential for HS-ST activity, whereas regions II
      (amino acids 65-101) and IV (amino acids 165-219) are unimportant with regard to
      substrate preference. It was also shown that the parental combination of regions
      I (amino acids 1-64) and V (amino acids 220-284) is essential for CS-ST activity.
      Photoaffinity labeling with [35S]3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      revealed that some inactive chimeras lost affinity for PAPS. These results
      suggested that an ordered structure formed by regions I, III, and V is required
      for HS-ST activity, especially for substrate preference and PAPS binding.

PMID- 9169021
TI  - The N-terminal sequence of Lactococcus lactis phosphoglucose isomerase purified
      by affinity chromatography differs from the other species.
AB  - A specific monoclonal antibody, M3A, was produced to rapidly purify Lactococcus
      lactis phosphoglucose isomerase (PGI) for amino acid sequence analysis. M3A
      recognized the Lac. lactis PGI specifically and sensitively with both enzyme
      linked immunosorbent assay and Western blot analysis. The enzyme was rapidly
      purified to a specific activity of 21.8 U/mg with a yield of 20% by a three-step
      procedure, including M3A-bound Sepharose chromatography. The specific activity of
      PGI was increased about 64.1-fold from the cell lysate. The molecular mass of
      Lac. lactis PGI was estimated to be about 50 kDa by SDS-PAGE. The N-terminal
      amino acid sequence of Lac. lactis PGI exhibited no significant similarity to
      other PGIs, except for a 52.6% identity to Bacillus stearothermophilus PGI A and
      PGI B. These results suggest that there might be some molecular types of PGI.

PMID- 9169022
TI  - Resonance Raman spectroscopic studies of cellobiose dehydrogenase from
      Phanerochaete chrysosporium.
AB  - Cellobiose dehydrogenase (CDH), an extracellular hemoflavoenzyme produced by
      cellulose-degrading cultures of Phanerochaete chrysosporium, oxidizes cellobiose
      to cellobionolactone. The enzyme contains one 6-coordinate, low-spin b-type heme
      and one FAD cofactor per monomeric protein. In this work, resonance Raman (RR)
      spectra are reported for the oxidized, reduced, and deflavo forms of CDH as well
      as the individual flavin and heme domains of the enzyme obtained by peptide
      proteolysis. The RR spectra of the flavin and heme groups of CDH were assigned by
      comparison to the spectra of other hemoflavoenzymes and model compounds.
      Proteolytic cleavage of the CDH domains had only a minimal spectroscopic effect
      on the vibrational modes of the heme and FAD cofactors. Excitation of the
      oxidized CDH holoenzyme at 413 or 442 nm resulted in photoreduction of the heme.
      However, the same excitation wavelength used on the deflavo form of the enzyme or
      on the heme domain alone did not cause photoreduction, indicating that
      photoinitiated electron transfer requires the FAD cofactor. These observations
      suggest an enzymatic mechanism whereby reducing equivalents obtained from the
      oxidation of cellobiose are transferred from the FAD to the heme. A similar
      mechanism has been proposed for flavocytochrome b2 of Saccharomyces cerevisiae
      which oxidizes lactate to pyruvate (A. Desbois et al., 1989, Biochemistry 28,
      8011-8022).

PMID- 9169023
TI  - Mapping the mechanism-based modification sites in L-aspartase from Escherichia
      coli.
AB  - Inactivation of the enzyme L-aspartase from Escherichia coli by the substrate
      analog aspartate beta-semialdehyde has previously been shown to occur by the
      mechanism-based conversion to the corresponding product aldehyde, followed by
      covalent modification of cysteine-273 (F. Giorgianni et al. (1995) Biochemistry
      34, 3529). Inactivation by the product analog, fumaric acid aldehyde (FAA), has
      now been examined directly by adding a reduction step to the modification
      protocol in order to stabilize the resulting enzyme-FAA derivative(s). HPLC and
      mass spectrometric analyses of proteolytic digests of inactivated L-aspartase
      have confirmed the modification at cysteine-273, and have also identified an
      additional modified peptide. The inactivation at this additional site involves a
      crosslink between cysteine-140 and an adjacent lysine. Site-directed mutagenesis
      studies have shown that cysteine-140 is a very reactive and accessible
      nucleophile that is not, however, directly involved in enzyme activity. The
      adjacent lysine-139 that is modified does appear to play a role in substrate
      binding. A double mutant in which both of the reactive cysteines have been
      replaced is almost completely insensitive to modification by these substrate and
      product analogs.

PMID- 9169024
TI  - Purification and characterization of a rat liver protein that recognizes CCAAT
      homologous sequences of the metallothionein promoter and trans-activates this
      promoter.
AB  - C'BP-1, a protein that binds to the MRE-c' region (-135 to -110) of the mouse
      metallothionein-I (MT-I) gene in metal-independent manner, was purified from rat
      liver nuclear extract by ion exchange and affinity chromatography. Analysis by
      SDS-PAGE, UV cross-linking, and glycerol gradient sedimentation, taken together,
      showed that C'BP-1 is a dimer of the 34-kDa polypeptides. Affinity-purified C'BP
      1 could significantly stimulate transcription from mouse MT-I gene promoter.
      DNase I footprinting with the purified protein identified two binding sites for
      C'BP-1 located at positions -135 to -100 and -210 to -175 with respect to the
      start site of MT-I gene transcription. Both C'BP-1 binding sequences were found
      to contain imperfect dyad of the CCAAT homology. C'BP-1 was shown to make
      critical contacts with the CCAAT homology by methylation interference analysis
      and competition electrophoretic mobility shift assay with mutants harboring
      alterations in the CCAAT homology. An antibody that specifically recognizes C/EBP
      delta partially supershifted C'BP-1/MRE-c' complex, suggesting that C'BP-1 is
      identical to C/EBP delta or is closely related to C/EBP delta.

PMID- 9169025
TI  - Production of the rat complement regulator, Crry, as an active soluble protein in
      Pichia pastoris.
AB  - In this report, we describe the use of the methylotrophic yeast Pichia pastoris
      for the production of the rat complement regulator, Crry. Crry normally exists as
      an intrinsic membrane protein containing six to seven short consensus repeats
      (SCRs), a transmembrane region, and a cytoplasmic tail. To produce Crry as a
      soluble recombinant protein, nucleotides encoding the five N-terminal SCRs from
      the rat Crry cDNA were amplified by PCR, and cloned into the P. pastoris
      expression vector, pPIC9. This vector contains the yeast alpha-factor signal
      sequence, thereby leading to secretion of recombinant protein. This construct was
      subsequently integrated into P. pastoris strain GS115 genomic DNA. Secreted
      soluble Crry was produced by induction of the AOX1 promoter with methanol.
      Recombinant Crry protein was purified to homogeneity by sequential Mono Q and
      Mono P chromatography. The protein was highly active toward the alternative and
      classical pathways of complement, inhibiting the latter by approximately 90% at a
      concentration of 15 nM. The P. pastoris system offers an efficient method for the
      production of soluble recombinant Crry. Production of active rat Crry offers
      opportunities to study long-term models of disease in rats, which has not been
      possible with available heterologous complement inhibitors.

PMID- 9169026
TI  - Selenophosphate synthetase: enzyme labeling studies with [gamma-32P]ATP, [beta
      32P]ATP, [8-14C]ATP, and [75Se]selenide.
AB  - Selenophosphate synthetase catalyzes a reaction in which ATP and selenide are
      converted to H3SeP03, H3P04, and AMP in a 1:1:1 ratio. Selenophosphate is derived
      from the gamma phosphoryl group and orthophosphate from the beta phosphoryl group
      of ATP. In the absence of selenide, a slow reaction in which ATP is converted
      quantitatively to 2 H3P04 and AMP occurs. Labeling experiments carried out to
      detect a putative enzyme-bound pyrophosphate intermediate in the overall reaction
      showed that up to 0.6 equivalent of the 32P label from [gamma-32P]ATP was bound
      to protein under enzyme turnover conditions, but only a negligible amount of 32P
      from [beta-32P]ATP was present. Thus, no Enz-PP intermediate was present in a
      detectable amount under the experimental conditions used. Isolated enzyme samples
      contained 75Se from 75Se-labeled selenide and [14C]AMP from [8-14C]ATP in amounts
      similar to the bound 32P from [gamma-32P]ATP, suggesting that two of the final
      products, selenophosphate and AMP, were the radioactive compounds detected in
      these experiments.

PMID- 9169027
TI  - Conformational preferences of a peptide corresponding to the major antigenic
      determinant of foot-and-mouth disease virus: implications for peptide-vaccine
      approaches.
AB  - The conformational preferences in solution of a peptide corresponding to the GH
      loop of the VP1 capsid protein from the foot-and-mouth disease virus were
      examined by proton nuclear magnetic resonance and circular dichroism. The GH loop
      is the major antigenic determinant of the virus and participates in cell
      attachment through an integrin-like Arg-Gly-Asp sequence. The synthetic peptide,
      corresponding to residues Gly132 to Ser162 of the VP1 capsid protein of the
      serotype O, is largely disordered in aqueous solution as shown by the absence of
      long- and medium-range NOE contacts and by random-like chemical shifts values.
      Helical contents in aqueous solution were estimated to be less than 10%, as
      determined by extrapolation of trifluoroethanol titration from CD measurements,
      in good agreement with estimations from NMR experiments. In the presence of 40%
      trifluoroethanol an alpha-helix, flanked by two proline residues between Asn12
      (Asn143 in the intact protein) and Leu28 (159), is induced. This contrasts with
      the 3(10) helix observed between residues Leu148 and Val155 in the crystal
      structure of the dithiothreitol-reduced virus, indicating that the cosolvent does
      not stabilize a residual, low-populated structure, similar to that in the intact
      virus. Several algorithms also fail to predict the structure found in the intact
      virus because these are based mainly on local sequence information. The lack of
      structure of the peptide in aqueous solution strongly suggests that the
      conformational determinants sufficient for the structure stabilization of this
      highly immunogenic antigen are mostly dictated by interactions of the loop with
      other regions of the virus structure, and do not arise from local amino acid
      sequence information. The ability of designed GH-VP1 peptides to neutralize anti
      virus antibodies is likely to arise from antibody-induced conformation of the
      peptide and its application as peptide vaccines is not straightforward.
      Similarly, insertion of these peptides in carriers or macromolecular assemblies
      as vaccine vectors would depend on the conformation adopted at the insertion site
      and its success cannot be predicted.

PMID- 9169028
TI  - Genetic aberrations in pediatric acute lymphoblastic leukemia by comparative
      genomic hybridization.
AB  - Classical cytogenetic analysis plays an important role in the diagnosis and
      classification of childhood acute lymphoblastic leukemia (ALL). However, poor in
      vitro growth of the malignant cells and suboptimal quality of metaphase spreads
      may sometimes cause false-negative findings (normal karyotype). We used
      comparative genomic hybridization (CGH) to study whether this new method is able
      to detect and characterize genetic aberrations not detected by karyotyping. CGH
      showed clonal genetic aberrations in 8 of 13 cases, most of which showed gains of
      several chromosomes, indicating hyperdiploidy. The sensitivity of CGH was
      sufficient to detect a small interstitial deletion of 6q. One karyotypically
      complex case was resolved by CGH showing a high-level amplification of DNA
      sequences originating from the 12p12-13. Interphase fluorescence in situ
      hybridization (FISH) analyses confirmed the CGH findings in 2 cases, validating
      the accuracy of CGH. In conclusion, CGH experiments established the known fact
      that hyperdiploidy is the most common finding in pediatric ALLs and that CGH may
      detect aberrations that are not seen in the G-banded karyotype. CGH was also able
      to further characterize genetic aberrations such as gene amplification, which is
      occasionally involved in pediatric ALL as well as in other leukemias.

PMID- 9169029
TI  - Telomeric fusions in cultured human fibroblasts as a source of genomic
      instability.
AB  - In a human fibroblast clone we studied the evolution, during culture propagation,
      of a dicentric chromosome consisting of the end-to-end association of the short
      arm of chromosome 5 and the long arm of chromosome 16. Dual-color fluorescence in
      situ hybridization (FISH) with painting probes allowed us to define the structure
      of a variety of derivative chromosomes and to identify the mechanisms by which
      they originated. Asymmetric interchanges involving the intercentromeric region of
      the dicentric, bridge-breakage-fusion events, or breaks followed by sister
      chromatid fusion, originate unstable hetero- or homodicentric chromosomes with
      deletion or duplication; breakages not followed by reunion, or intradicentric
      recombination, presumably originate stable rearranged monocentric chromosomes.
      The variety of the derivatives is extremely large because the observed events may
      involve any site of the intercentromeric region, although the majority of them
      occurs after a break in 16qh. The results of this investigation document the
      evolution through successive steps of a telomeric fusion, a chromosome anomaly
      frequently observed in tumor and senescent cells. They also demonstrate that in
      cultured cells of normal origin, starting with this anomaly, various chromosomal
      mechanisms may produce translocations, duplications, and deletions. The karyotype
      instability produced by a telomeric fusion can be relevant for carcinogenesis
      because it may generate genetic changes critical in the multistep process of
      transformation.

PMID- 9169030
TI  - Two unbalanced translocations, t(12;22)(p13;q11) and t(12;?)(p13;?), in an
      aggressive chronic B-cell leukemia: TEL gene analysis using FISH.
AB  - The translocation t(12;22)(p13;q11) has been consistently described in myeloid
      malignancies and shown to result from a fusion between the TEL and MN1 genes.
      Previously described deletions of 12p in acute lymphoblastic leukemias have been
      recently shown to harbor undetected translocations involving the TEL gene at
      12p13. We document a case of an aggressive chronic B-cell leukemia whose cells
      had trisomy 12 and two unbalanced translocations involving 12p13, including a
      t(12;22)(p13;q11) as shown by conventional cytogenetics and fluorescence in situ
      hybridization (FISH). The 12p13 breakpoint of the t(12;22)(p13;q11) was telomeric
      to the TEL gene, and the second unbalanced translocation with breakpoint 12p13
      resulted in the deletion of TEL. This case demonstrates that TEL gene deletions
      may be relevant in cases of mature B-lymphoproliferative diseases.

PMID- 9169031
TI  - Cytogenetic and molecular genetic analysis of a pediatric pleomorphic sarcoma
      reveals similarities to adult malignant fibrous histiocytoma.
AB  - Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma
      removed from the left atrium of a 15-year-old girl. Histologic analysis was
      consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH).
      Although MFH is the most common soft-tissue sarcoma of late adulthood. It is
      extremely rare in childhood and its existence in the pediatric population remains
      controversial. Cytogenetic analysis revealed several alterations previously
      associated with adult MFH, including abnormalities of chromosomal bands 11p11 and
      19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and
      double minute chromosomes (dmin) suggestive of gene amplification. We therefore
      screened the case for amplification of genes localized to chromosomal bands 12q13
      14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which
      are frequently amplified and overexpressed in adult MFH. Southern and Northern
      blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our
      knowledge, such coamplification studies of the 12q13-14 amplicon have not been
      previously detected in pediatric MFH. Our results provide cytogenetic and
      molecular genetic evidence that pediatric and adult MFH are histogenetically
      related entities.

PMID- 9169032
TI  - Identification of chromosome changes in acute myeloid leukemia (AML-M2) by
      molecular cytogenetics.
AB  - Karyotyping with fluorescence in situ hybridization (FISH) is reported in two
      rare cases of AML-M2 FAB. In the first case FISH analysis confirmed the presence
      of a t(7;11)(p15:p15) translocation in a complex karyotype that also showed an
      unbalanced translocation involving the other chromosome 7, a rare rearrangement
      between chromosomes 9 and 20, and four or five copies of a small marker derived
      from chromosome 9. In the second case whole chromosome painting with probes for
      chromosomes 8, 14, and 21 revealed the presence of a masked t(8;21) translocation
      in which one chromosome 14 was involved in a newly discovered rearrangement,
      i.e., t(8;14;21)(q22-q24;q11;q22). Moreover , double color FISH using ETO-CDR P1
      probe and a cosmid for the 5' part of AML-1 on chromosome 21 showed a two color
      signal on the 8q-, suggesting a recombination between ETO and AML 1. Molecular
      cytogenetics overcomes limitation of chromosome banding in the interpretation of
      complex rearrangements.

PMID- 9169033
TI  - The expression of common fragile sites and genetic predisposition to squamous
      cell lung cancers.
AB  - The chromosomal aberration rates (including gaps and breaks) and expression
      frequency of fragile sites were determined in peripheral blood lymphocytes
      cultured with TC 199 medium from 8 patients with squamous cell lung cancer, 10 of
      their first-degree relatives, and 12 healthy control subjects. As a result of
      cytogenetic evaluation, both the chromosomal aberration rates and expression
      frequencies of common fragile sites observed in patients and their relatives were
      significantly higher than those in healthy control subjects. Our results showed
      that common fragile sites might be unstable factors in the human genome, and
      their expression might be affected by some genetic and environmental factors. As
      a result of this they might play an important role in genetic predisposition to
      lung cancer. The high expression of fra(3)(p14) in patients and their relatives
      may be a valid marker for genetic predisposition to lung cancer.

PMID- 9169034
TI  - Association of hereditary angioedema and hereditary breast cancer.
AB  - A family is presented in whom hereditary angioedema (HAE) and hereditary breast
      cancer were coexistent, an association not previously reported. A potential for
      genetic and treatment-related interactions between the two conditions exists. The
      use of the hormonal agent danazol to suppress HAE is unlikely to adversely affect
      the development or outcome of breast cancer. Surgery, chemotherapy, and
      radiotherapy were received by affected family members, without triggering edema.
      Whether hormonal breast cancer treatment affects the suppression of HAE by
      danazol remains unknown.

PMID- 9169035
TI  - Chromosomal aberration in lipoblastoma: a case with 46,XX,ins(8;6)(q11.2;q13q27).
AB  - Chromosomal aberrations involving 8q11.2 have been reported in lipoblastoma. We
      report here a case of lipoblastoma with new chromosomal aberration.
      46,XX,ins(8;6)(q11.2;q13q27). Cytogenetic analysis would facilitate the clinical
      differentiation between myxoid liposarcoma and the pathologically similar
      lipoblastoma and the identification of genetic loci related to cellular growth.

PMID- 9169036
TI  - t(High) frequency of telomeric associations in human ovarian surface epithelial
      cells transformed by human papilloma viral oncogenes.
AB  - Viral oncogenes are commonly used to transform and extend the in vitro life span
      of human epithelial cells. We have established 7 cell lines of human ovarian
      surface epithelial cells using human papilloma viral oncogenes (HPV-E6E7 ORFs).
      Cytogenetic analysis of the cell lines revealed a high frequency of telomeric
      associations ranging from 30% to 100% of the metaphases examined. The short arms
      of chromosomes 16, 19, 21, and 22 showed a higher rate of telomeric association.
      Telomeric association with other chromosomal ends appears to be random. Fusion of
      2 chromosomes ends may contribute to the genomic instability of transformed cells
      and lead to further genetic alterations involved in malignant transformation such
      as gene amplication and loss of heterozygosity. This is the first report
      describing a high frequency of telomeric associations in human ovarian epithelial
      cells transformed by HPV oncogenes.

PMID- 9169037
TI  - Clinical correlations of immunophenotypic variations and the presence of trisomy
      12 in B-cell chronic lymphocytic leukemia.
AB  - In a prospective study of 93 consecutive untreated patients with B-cell chronic
      lymphocytic leukemia, we examined the clinical relevance of surface
      immunoglobulin (sIg) heavy chain (HC) and light chain (LC) isotypes, CD11c or
      CD25 expression, and the presence of trisomy 12 by fluorescence in situ
      hybridization (FISH). Careful morphologic evaluation was performed to exclude
      patients with other forms of chronic lymphoid leukemias, including mantle cell
      lymphoma, prolymphocytic leukemia, and leukemia phase of lymphoma. In addition,
      clonally restricted sIg and CD5 surface determinant were expressed in all
      patients. Clinical presentation, including blood cell counts, clinical stage, and
      organomegaly, did not correlate with any of the measured variables. After a
      median follow-up period of 3 years, the particular HC or LC isotype or CD11c
      expression did not correlate with either disease progression or treatment-free
      survival. However, trisomy 12 and CD25 expressions were both associated with
      accelerated disease progression and a shorter treatment-free survival time. Our
      results confirm the adverse prognostic significance of trisomy 12 expression in
      chronic lymphocytic leukemia and suggest that CD25 expression may have an
      unfavorable clinical impact.

PMID- 9169038
TI  - Cytogenetic and molecular studies of siblings with ataxia telangiectasia followed
      for 7 years.
AB  - We present cytogenetic, immunologic, and molecular data obtained over 7 years
      from a family with ataxia telangiectasia (AT) including 2 affected children and
      their unaffected sibling, and their obligate heterozygous parents. In a period of
      3 years, the T lymphocytes from both AT patients showed clonal rearrangements of
      chromosomes 7 and 14 at specific bands (7p13, 7q35, 14q12, and 14q32), where loci
      for the Ig and TCH genes are located. A molecular study was carried out on
      peripheral blood and bone marrow samples from both patients using Southern blot
      and PCR for Ig and TCR genes. A monoclonal population for TCR gamma was observed
      in one of the two affected children, but only in peripheral blood.

PMID- 9169039
TI  - Homozygous deletion of the neurofibromatosis-1 gene in the tumor of a patient
      with neuroblastoma.
AB  - The neurofibromatosis type 1 (von Recklinghausen, NF1) gene has been proposed as
      a suppressor gene in tumors associated with neurofibromatosis. Recent
      publications have indicated that the NF1 gene can be rearranged in neuroblastoma
      cell lines. We analyzed DNA from a neuroblastoma patient with NF1 inherited as a
      familial trait on the paternal side. Using PCR and Southern techniques we showed
      that the patient had a constitutional deletion of several exons of the paternally
      derived NF1 gene and that the maternal copy of the gene had been deleted in the
      tumor of the patient. This is the first instance of a homozygous deletion
      reported in a primary neuroblastoma tumor. This suggests that NF1 inactivation in
      involved in the development or progression of some neuroblastomas in agreement
      with the hypothesized two hit model of inactivation for a tumor suppressor. These
      results are concordant with other groups that have detected unbalanced
      translocations t(1;17) in neuroblastoma tumors, with a breakpoint in chromosome
      17 that may coincide with the location of the NF1 gene.

PMID- 9169040
TI  - Acquired monosomy 7 in donor cells in a patient treated for acute lymphoblastic
      leukemia with bone marrow transplantation.
AB  - Two years after a bone marrow transplant (BMT) from his haploidentical mother, a
      28-year-old male with a history of acute lymphoblastic leukemia (ALI.) developed
      myelodysplastic syndrome (MDS) with monosomy 7 in his female bone marrow cells.
      Follow-up cytogenetic studies, including fluorescence in situ hybridization
      (FISH) performed twenty-seven and thirty-one months post-BMT consistently showed
      a female chromosome pattern with monosomy 7. Thirty-six and thirty-nine months
      post-BMT, further clonal evolution occurred, with the appearance of a sideline of
      the female cells that first expressed a del(10)(p11.2) and then developed a
      translocation, t(10;21)(p11.2;q22), in addition to the monosomy 7. Cytogenetic
      monitoring of this male patient helped to reveal a rare case of early MDS in
      transplanted donor cells and evolution of the acquired abnormal clone by
      identifying chromosomal alterations in the donated female bone marrow cells.

PMID- 9169041
TI  - Molecular characterization of a complex chromosomal rearrangement in a
      pleomorphic salivary gland adenoma involving the 3'-UTR of HMGIC.
AB  - Recently, the high mobility group protein gene, HMGIC, was identified as a common
      genetic denominator in benign tumors with chromosome 12q13-15 aberrations, such
      as lipomas, uterine leiomyomas, pleomorphic adenoma of the salivary glands,
      hamartomas of breast and lung, angiomyxomas, and endometrial polyps. In most
      cases, the rearrangements resulted in the separation of the three HMGIC DNA
      binding motifs from the acidic carboxy-terminal tail. Here, we report about the
      molecular characterization of a case of pleomorphic adenoma carrying a
      t(1;12)(p22;q15). Studies were performed on a cell line derived from the primary
      tumor, i.e., cell line Ad-312/SV40. Although the chromosome 12 breakpoint was
      initially mapped more than 1 Mb distal to the HMGIC gene by fluorescence in situ
      hybridization (FISH) analysis, the present molecular studies reveal a more
      complex chromosomal rearrangement that directly affects the HMGIC gene. Using 3'
      RACE analysis, a HMGIC fusion transcript was detected that contained the complete
      HMGIC, coding region but lacked the putative mRNA destabilizing AUUUA motifs that
      are normally present in the 3'-UTR of HMGIC. Wild-type HMGIC transcripts were
      also detected in the tumor cells. The results suggest that alterations in the 3'
      noncoding region of HMGIC may have to be considered as pathogenetically relevant.

PMID- 9169042
TI  - c-myc amplification in a preleukemia patient with trisomy 4 and double minutes:
      review of the unique coexistence of these two chromosome abnormalities in acute
      myelogenous leukemia.
AB  - Cytogenetic analysis of the bone marrow from a woman with preleukemia showed an
      aberrant clone with trisomy 4, double minutes, and a translocation
      t(8;9)(q21;q34). Fluorescence in situ hybridization (FISH) demonstrated that the
      double minutes were c-myc amplifications. A review of six cases in the literature
      and the present case with trisomy 4 and double minutes showed a preponderance of
      females and that the patients were mostly elderly. The acute myelogenous leukemia
      (AML) in these patients was either FAB subtype M2 or M4. In two out of seven
      cases, the double minutes were c-myc amplicons. The patients responded to
      treatment and there was karyotypic normalization during remission. There was no
      strong evidence of exposure to genotoxic agents.

PMID- 9169043
TI  - Myelodysplastic syndrome presenting with clonal rearrangement isolated to
      chromosomal region 1q.
AB  - Myelodysplastic syndrome (MDS) is a malignant hematologic disorder that may
      present with clinical features consistent with the diagnosis of severe aplastic
      anemia (SAA). Distinguishing the two disorders may depend on the presence of a
      clonal chromosomal abnormality. In the following, we report a case of MDS
      associated with what we believe to be a previously unreported clonal abnormality
      of chromosome 1q, a finding that enabled us to distinguish between MDS and SAA.

PMID- 9169044
TI  - A new case of trisomy 21 in a patient with an acute nonlymphocytic leukemia (M5b)

PMID- 9169045
TI  - Microtubule dependence of chromosome cycles in Xenopus laevis blastomeres under
      the influence of a DNA synthesis inhibitor, aphidicolin.
AB  - The spindle-assembly checkpoint of the cell cycle develops in Xenopus laevis
      embryos at the midblastula transition (MBT). Our previous experiments using
      animal-cap blastomeres indicate that the checkpoint is regulated by a mechanism
      that depends on age, but not on the nucleocytoplasmic (N/C) ratio (Clute and
      Masui, 1995). In the present study, the time of appearance of the spindle
      assembly checkpoint is examined in animal-cap blastomeres whose N/C ratio is
      reduced by treatment with aphidicolin. Animal-cap blastomeres treated with
      aphidicolin from the 2-cell stage cleave more slowly after 4th cleavage, in a
      dose-dependent manner, but cleavage and chromosome cycles continue up to the 11th
      to 13th cleavage and then arrest. Blastomeres treated with aphidicolin have a
      reduced DNA content and N/C ratio compared to control blastomeres of the same
      age. Nevertheless, nocodazole-sensitive chromosome cycles appear at the same time
      as in control blastomeres, at 3 to 5 hr after 5th cleavage, regardless of the N/C
      ratio. The arrest in interphase caused by treating blastula stage animals caps
      with aphidicolin can be reversed by treatment with caffeine. The caffeine-induced
      mitosis becomes sensitive to nocodazole after the MBT, but not before. Therefore,
      the same mechanism which stabilizes maturation-promoting factor activity in the
      absence of a mitotic spindle also operates after the MBT in blastomeres that are
      treated with aphidicolin, if mitosis is induced by caffeine. This mechanism may
      involve the translation of a maternal mRNA at the time of the MBT, as suggested
      previously.

PMID- 9169046
TI  - N-cadherin promotes the commitment and differentiation of skeletal muscle
      precursor cells.
AB  - Cells with the potential to form skeletal muscle are present in the chick embryo
      prior to gastrulation. Muscle differentiation begins after gastrulation within
      the somites. The role of cadherin-mediated adhesion in the commitment and
      differentiation of skeletal muscle precursor cells was examined by analyzing the
      expression of cell-cell adhesion molecules in cultures of epiblast, segmental
      plate, and somite cells and by determining the effects of adhesion-perturbing
      antibodies on the accumulation of MyoD and sarcomeric myosin. Cultured primitive
      streak stage epiblast cells downregulate E-cadherin and upregulate N-cadherin.
      This switch in cadherin expression also occurs in vivo as epiblast cells enter
      the primitive streak. Although MyoD protein is present in cells with N- or E
      cadherin, only cells with N-cadherin differentiate into skeletal muscle. In
      contrast to the primitive streak stage epiblast cells, prestreak epiblast cells
      maintain the expression of E-cadherin in vitro. While the majority of prestreak
      cells contain MyoD, only a few synthesize myosin. Treatment of primitive streak
      stage epiblast cells with function-perturbing antibodies to N-cadherin resulted
      in an inhibition of myosin accumulation and a decrease in the percentage of cells
      with MyoD. Segmental plate and somite cells are similar to primitive streak stage
      epiblast cells in that most differentiated into skeletal muscle when cultured in
      serum-free medium. While function-perturbing antibodies to N-cadherin inhibited
      the accumulation of myosin in these mesoderm cells, the number of MyoD positive
      cells was unaffected in somite cultures and only partially reduced in segmental
      plate cultures. These results suggest that N-cadherin-mediated cell-cell adhesion
      is involved in both the commitment of muscle precursors and their terminal
      differentiation.

PMID- 9169047
TI  - Multiple Ras signals pattern the Drosophila ovarian follicle cells.
AB  - During Drosophila oogenesis, spatially restricted activity of the TORPEDO
      receptor tyrosine kinase first recruits follicle cells adjacent to the oocyte to
      a posterior cell fate and then specifies dorsal follicle cells. Another receptor
      tyrosine kinase, BREATHLESS, stimulates migration of the anterior follicle cells
      known as border cells. Since Ras is known to mediate many receptor tyrosine
      kinase effects, we have investigated the role of Ras in follicle cell fate
      determination, differentiation, and migration throughout oogenesis. Early ectopic
      Ras activity induced transient expression of posterior follicle cell markers in
      anterior follicle cells, but did not inhibit anterior differentiation. Later
      ectopic Ras activity inhibited anterior follicle cell differentiation but did not
      induce posterior marker expression. Complete transformation of anterior follicle
      cells to posterior follicle cells required early ectopic Ras activity in egg
      chambers where terminal differentiation of anterior cells was inhibited. These
      results suggest that, in vivo as in vitro, Ras can have diverse effects on
      different cells, but, in addition, Ras activity can have different effects on the
      same cells at different stages in their development.

PMID- 9169048
TI  - Sorting of the initial cell types in Dictyostelium is dependent on the tipA gene.
AB  - About 8 hr after the initiation of development in Dictyostelium discoideum, a few
      randomly scattered cells express prestalk specific genes and subsequently sort
      out to the top of the aggregate where they form a tip. The tip elongates and
      forms the anterior of the migrating slug before differentiating into a stalk
      which supports the ball of spores in a mature fruiting body. Using REMI
      mutagenesis we isolated a mutant strain, AK244, in which the initial aggregate
      subdivides to give a highly papillated surface. This mutant fails to form slugs
      and appears to have a defect in sorting of prestalk cells. The disrupted gene,
      tipA, encodes a novel 83-kDa protein and is preferentially expressed in PST-O
      cells after the cell types have sorted out. Mutant strains that lack TipA express
      the prestalk-specific gene ecmA at reduced levels and form very few spores. These
      defects cannot be overcome by developing the mutant cells in the presence of wild
      type cells. Thus, TipA acts in a cell-autonomous manner at an early stage in
      development. Using strains carrying reporter constructs, we found that mutant
      cells expressing a prestalk marker remain dispersed in the aggregates. Prespore
      cells appear to sort such that the base is free of cells expressing cell-type
      specific markers. Even after 20 hr of development, when wild-type cells are
      undergoing terminal differentiation, prestalk cells in tipA mutants form very
      small clumps, most of which fail to sort to the periphery or the tops of
      aggregates. The tipA gene appears to play an essential role in the sorting of the
      initial cell types.

PMID- 9169049
TI  - Fibroblast growth factor receptor-1 (FGFR-1) is essential for normal neural tube
      and limb development.
AB  - Fibroblast growth factor receptor-1 (FGFR-1) is a membrane-spanning tyrosine
      kinase that serves as a high-affinity receptor for fibroblast growth factors. It
      has recently been shown that FGFR-1 mutant embryos die during gastrulation
      displaying severe growth retardation and defective mesodermal structures. This
      early lethality has obscured functions of FGFR-1 that might occur later in
      development. To circumvent these embryonic defects, we generated chimeras by
      injecting FGFR-1-deficient (R1-/-) ES cells into wild-type blastocysts. We found
      that the fgfr-1 gene plays an important role after gastrulation and that it acts
      in a cell-autonomous fashion. Embryos with a high contribution of R1-/- cells
      replicate the FGFR-1 null phenotype and die during gastrulation. In contrast, the
      majority of embryos with a low contribution of R1-/- cells complete gastrulation
      and display malformations of posterior structures at later stages of
      embryogenesis. These abnormalities include truncation of embryonic structures,
      limb bud malformation, partial duplication of the neural tube, tail distortion,
      and spina bifida caused by the amplification of neural tissue in the posterior
      portion of the spinal cord. Thus, FGFR-1 plays a role in neurulation, suggesting
      that there may be a connection between FGFR-1-mediated signal pathways and neural
      tube defects, the most common malformations in the human central nervous system.

PMID- 9169050
TI  - In vivo regulation of cytostatic activity in Xenopus metaphase II-arrested
      oocytes.
AB  - Metaphase II arrest of Xenopus oocyte is characterized by the presence of M-phase
      promoting factor (MPF) and of a microtubular spindle, both of which are stable in
      the presence of protein synthesis inhibitors. We studied in vivo this equilibrium
      state that is settled during meiotic maturation. At time of germinal vesicle
      breakdown (GVBD), cdc2 kinase and MAP kinase activities are stimulated. A
      component of the cyclin ubiquitin ligase, CDC27, is phosphorylated at the same
      time and remains phosphorylated until fertilization, indicating that an important
      component of the ligase complex is modified as early as GVBD. During a first
      period extending from GVBD until the cortical anchorage of the metaphase II
      spindle, homogeneous pools of cdc2 kinase and mitogen-activated protein (MAP)
      kinase activities are present in oocyte and are strictly dependent on protein
      turnover, since protein synthesis inhibition induces their total inactivation and
      drives oocytes into interphase. The metaphase II spindle, once anchored into the
      cortex, is no more sensitive to protein synthesis inhibition, likewise MAP kinase
      activity. During this cellular arrest, cdc2 kinase is divided into two distinctly
      regulated pools. The first one contains cyclin B that actively turns over and is
      subjected to a microtubular checkpoint. The second one is stable. Alteration of
      intracellular compartmentation of metaphase II oocytes either by gentle
      centrifugation or by cold shock inactivates MAP kinase and targets all cyclin B
      molecules for full destruction. We therefore suggest that MAP kinase participates
      to the cytostatic activity by preventing part of cyclin B molecules from entering
      the ubiquitination/degradation machinery which is still turned on in metaphase II
      oocytes.

PMID- 9169051
TI  - Cytoplasmically anchored plakoglobin induces a WNT-like phenotype in Xenopus.
AB  - Plakoglobin is one of two vertebrate proteins closely related to the Drosophila
      segment polarity gene product armadillo. Overexpression of plakoglobin induces
      neural axis duplication in Xenopus and the exogenous plakoglobin is localized to
      nuclei (Karnovsky, A., and Klymkowsky, M. W., Proc. Natl. Acad. Sci. USA 92,
      4255, 1995; Rubenstein, A., et al., Dev. Genet., 1997, in press). We have carried
      out a series of experiments to test whether the nuclear localization of
      plakoglobin is required for its inductive effects. Prior to the midblastula
      transition exogenous plakoglobin is cytoplasmic and concentrated in the cortical
      regions of blastomeres; after the midblastula transition exogenous plakoglobin
      accumulates in embryonic nuclei. The addition of a "nuclear localization
      sequence" does not change the timing of plakoglobin's nuclear localization,
      suggesting that it is anchored in the cytoplasm prior to the midblastula
      transition. Next, we constructed two "membrane-anchored" forms of plakoglobin.
      These are exclusively cytoplasmic; yet both were as effective at producing a "Wnt
      like" axis duplication as were "free," unfettered forms of plakoglobin. Moreover,
      expression of anchored plakoglobins had no apparent effect on the cytoplasmic or
      nuclear levels of beta-catenin. These data indicate that plakoglobin can act
      cytoplasmically to generate a WNT-like phenotype. Taken together with the
      ventralizing effects of a mutant from of the XTcf-3 transcription factor,
      described by Molenaar et al. Cell 86, 391, 1996, we speculate that in the early
      Xenopus embryo, activation of plakoglobin (or beta-catenin) inhibits the activity
      of XTcf-3 or a XTcf-3-like factor.

PMID- 9169052
TI  - Activation of the Wnt signaling pathway: a molecular mechanism for lithium
      action.
AB  - Glycogen synthase kinase-3 beta (GSK-3 beta/zeste-white-3/shaggy) is a negative
      regulator of the wnt signaling pathway which plays a central role in the
      development of invertebrates and vertebrates; loss of function and dominant
      negative mutations in GSK-3 beta lead to activation of the wnt pathway in
      Drosophila and Xenopus. We now provide evidence that lithium activates downstream
      components of the wnt signaling pathway in vivo, leading to accumulation of beta
      catenin protein. Our data indicate that this activation of the wnt pathway is a
      consequence of inhibition of GSK-3 beta by lithium. Using a novel assay for GSK-3
      beta in oocytes, we show that lithium inhibits GSK-3 beta from species as diverse
      as Dictyostelium discoideum and Xenopus laevis, providing a biochemical mechanism
      for the action of lithium on the development of these organisms. Lithium
      treatment also leads to activation of an AP-1-luciferase reporter in Xenopus
      embryos, consistent with previous observations that GSK-3 beta inhibits c-jun
      activity. Activation of the wnt pathway with a dominant negative form of GSK-3
      beta is inhibited by myo-inositol, similar to the previously described effect of
      coinjecting myo-inositol with lithium. The mechanism by which myo-inositol
      inhibits both dominant negative GSK-3 beta and lithium remains uncertain.

PMID- 9169053
TI  - Delta-1 is a regulator of neurogenesis in the vertebrate retina.
AB  - In the retina, cell fate determination is thought to be regulated by a series of
      local cell-cell interactions. Evidence suggests that retinal precursors utilize
      Notch-mediated intercellular signaling to regulate their fates. However, the
      identity of the endogenous ligand and its role in the Notch-signaling pathway is
      not well understood. We have identified C-Delta-1 as the putative endogenous
      ligand for Notch, in the developing chick retina. C-Delta-1 is coexpressed
      spatially and temporally with C-Notch-1 and their expression is associated with
      the temporal aspects of cell birth in the developing retina. This suggests that
      Delta-Notch signaling is utilized to maintain progenitors in an uncommitted state
      and that a subtle fluctuation in this signaling helps to sort out competent cells
      during successive cell-fate determination. We have tested the latter possibility
      in the specification of the ganglion cells. In early stages of retinal
      development when ganglion cells are the predominant cells born, decreasing C
      Delta-1 expression with antisense oligonucleotides increases the proportion of
      RA4 antigen-expressing ganglion cells which are recruited predominantly in the
      periphery. Conversely, use of exogenous Drosophila Delta leads to a decrease in
      the RA4 antigen-expressing ganglion cells. Our results suggest that C-Delta-1
      activation of the Notch pathway regulates the specification of retinal neurons in
      general and of ganglion cells in particular.

PMID- 9169054
TI  - Inhibition of chondrogenesis by Wnt gene expression in vivo and in vitro.
AB  - The Wnt family of secreted signaling proteins are implicated in regulating
      morphogenesis and tissue patterning in a wide variety of organ systems. Several
      Wnt genes are expressed in the developing limbs and head, implying roles in
      skeletal development. To explore these functions, we have used retroviral gene
      transfer to express Wnt-1 ectopically in the limb buds and craniofacial region of
      chick embryos. Infection of wing buds at stage 17 and tissues in the head at
      stage 10 resulted in skeletal abnormalities whose most consistent defects
      suggested a localized failure of cartilage formation. To test this hypothesis, we
      infected micromass cultures of prechondrogenic mesenchyme in vitro and found that
      expression of Wnt-1 caused a severe block in chondrogenesis. Wnt-7a, a gene
      endogenously expressed in the limb and facial ectoderm, had a similar inhibitory
      effect. Further analysis of this phenomenon in vitro showed that Wnt-1 and Wnt-7a
      had mitogenic effects only in early prechondrogenic mesenchyme, that cell
      aggregation and formation of the prechondrogenic blastema occurred normally, and
      that the block to differentiation was at the late-blastema/early-chondroblast
      stage. These results indicate that Wnt signals can have specific inhibitory
      effects on cytodifferentiation and suggest that one function of endogenous Wnt
      proteins in the limbs and face may be to influence skeletal morphology by
      localized inhibition of chondrogenesis.

PMID- 9169055
TI  - Lens induction by Pax-6 in Xenopus laevis.
AB  - Despite extensive study following the pioneering work of Spemann on lens
      development (Spemann, H. (1901) Verh. Anat. Ges. 15, 61-79) and the subsequent
      establishment of the concept of embryonic induction, the molecular mechanism of
      vertebrate lens induction remains largely unknown. Here we report that in Xenopus
      expression of Pax-6 results in lens formation in a cell autonomous manner. In
      animal cap experiments, Pax-6 induced expression of the lens-specific marker beta
      B1-crystallin without inducing the general neural marker NCAM. Ectopic Pax-6
      expression also resulted in the formation of ectopic lenses in whole embryos as
      well as in animal cap explants indicating that in vertebrates, as well as
      Drosophila (Halder, G., Callaerts, P., and Gehring, W.J. (1995) Science 267, 1788
      1792), Pax-6 can direct the development of major components of the eye.
      Interestingly, ectopic lenses formed in whole embryos without association with
      neural tissue. Treatments giving rise to anterior neural tissue in animal cap
      explants resulted in the expression of both beta B1-crystallin and Pax-6. Given
      the ability of Pax-6 to direct lens formation, we propose that the establishment
      of Pax-6 expression in the presumptive lens ectoderm during normal development is
      likely to be a critical response of lens-competent ectoderm to early lens
      inducers.

PMID- 9169056
TI  - Polycyclic aromatic hydrocarbon-DNA adducts in beluga whales from the Arctic.
AB  - The Arctic is still relatively pristine in nature, but it is also vulnerable to
      pollution because contaminants originating from midlatitudes are transported to
      the Arctic by atmospheric processes, ocean currents, and rivers (Muir et al.,
      1992). Recognition of this fact of Arctic vulnerability has resulted in a
      Declaration on the Protection of the Arctic Environment by eight Arctic
      countries. A manifest aim of this declaration is to develop an Arctic Monitoring
      and Assessment Program. We report here on the presence of measurable levels of
      polycyclic aromatic hydrocarbon-DNA adducts, including relatively high levels in
      Arctic beluga (Delphinapterus leucas). These results lend support to the value of
      developing biological assessment programs for Arctic wildlife.

PMID- 9169057
TI  - High blood cadmium levels are not associated with consumption of traditional food
      among the Inuit of Nunavik.
AB  - High levels of cadmium in the liver and kidneys of caribous and sea mammals of
      the Canadian Arctic have led to recommendations to remove such offal from the
      traditional diet. Blood cadmium levels have been found to be very high in samples
      of Inuit volunteers, hence the hypothesis that the Inuit might be exposed to
      cadmium through their diet. This survey of a population-based random sample of
      Nunavik residents (n = 518) confirms that blood cadmium of Inuit is indeed very
      high by comparison to published reports. Blood cadmium levels are closely
      associated with the current smoking status and are independent of dietary
      patterns among nonsmokers. Plasma omega-3 fatty acids concentrations have been
      used to assess the reliability of the dietary information collected by
      questionnaires and to test for any association of blood cadmium with the
      consumption of sea mammals. Blood cadmium levels are not related to the reported
      consumption of sea mammals. Blood cadmium levels are very high among smokers and
      are associated with levels of exposure to tobacco. Among nonsmoking Inuit, blood
      cadmium levels are comparable with those reported in nonsmokers elsewhere in the
      world. In reference to international standards, blood cadmium concentrations are
      high enough among the Inuit to warrant energetic public health interventions.

PMID- 9169058
TI  - Restriction of cadmium transfer to eggs from laying hens exposed to cadmium.
AB  - The transfer of Cd to eggs of white Leghorn laying hens has been shown to be
      restricted. After Cd was injected ip into laying hens, the Cd concentrations in
      the blood, livers, ovaries, and eggs were measured. Although the Cd
      concentrations in the maternal blood and livers increased remarkably at certain
      levels of administrations, the Cd concentration in the yolks of eggs was not
      significantly increased, and was less than 0.04 microgram/g wet weight. After egg
      production stopped in the highest injected group (7.5 mg Cd/kg), Cd in the yolks
      of eggs had an accumulated range of 0.02-0.03 microgram/g wet weight. This was
      despite the high Cd accumulation in the liver. Furthermore, the Cd concentration
      in the follicle walls of the ovary increased and was 13- to 52-fold higher than
      in the follicle yolks. An additional experiment was conducted in order to
      estimate whether hatching success is affected by the Cd in the laid eggs of Cd
      injected laying hens. The ratio of hatching success in the 0.3 or 1.2 micrograms
      Cd/egg-injected groups was similar to that in the saline-injected group,
      indicating that a small amount of Cd in the eggs might exert no marked influence
      on the hatching success. In conclusion, Cd transfer from laying hen to eggs was
      restricted after the maternal bird was exposed to Cd. Furthermore, Cd accumulates
      in the follicle walls of ovary. These results suggest that the follicle walls
      might play a role in protecting the follicle yolks against Cd toxicity.

PMID- 9169059
TI  - Elimination of beta-hexachlorocyclohexane in occupationally exposed persons.
AB  - The elimination of beta-hexachlorocyclohexane (beta-HCH) in humans was
      investigated in a group of 40 former workers of a lindane-producing plant by
      analyzing at least 2 blood specimens (3 specimens in 3 workers) from different
      time points. Assuming a first-order kinetic model for excretion, the median half
      life of beta-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr
      calculated by concentrations in extractable lipids. In univariate analyses an
      influence of age, percent body fat, and liver disease (additionally in whole
      blood an influence of contents of extractable lipids) on clearance was observed.
      All factors show a positive correlation with half-life. According to a multiple
      regression model, influence of percent body fat calculated according to
      Deurenberg et al. (1991) is an important covariate in the description of the
      variations of the clearance rate (calculated on the basis of extractable lipids)
      of beta-HCH. The data support the assumption of first-order kinetics.

PMID- 9169060
TI  - Simulated dermal contamination with capillary samples and field cholinesterase
      biomonitoring.
AB  - The extensive international use of organophosphorus compounds (OP) results in
      numerous acute intoxications each year. OPs inhibit acetylcholinesterase, the
      enzyme responsible for breaking down the neurotransmitter acetylcholine. The
      World Health Organization recognizes cholinesterase (ChE) biomonitoring as a
      preventive measure against OP overexposure. The aim of this study was to
      determine if dermal OP contamination could interfere with current field ChE
      biomonitoring assays, which use a fingerstick blood sample. In this study we also
      sought to determine if high levels of a plasma enzyme, A-esterase, could protect
      ChE from inhibition by hydrolyzing environmentally generated oxons potentially
      present in a fingerstick sample. A heparinized venous blood sample was collected
      from a volunteer. Erythrocyte acetylcholinesterase (AChE) and plasma
      butyrylcholinesterase (PChE) activities were measured using a field-based
      colorimetric cholinesterase kit. ChE dose-response curves were constructed by
      allowing 10-microliters blood samples to contact environmentally realistic levels
      of OP thioate and oxon for 10 s. An inhibition threshold could not be established
      for PChE when exposed to oxon within the time necessary to perform a fingerstick
      analysis. AChE was also inhibited by trace amounts of oxon consistent with
      previously reported environmental levels. These findings suggest that the
      reliability of field-based biomonitoring results is limited if OP residues remain
      on a skin surface at the time of sample collection. A-esterase's role in
      protecting ChE activity was investigated using capillary and venous blood from 30
      unexposed individuals. Baseline ChE activities were measured, as were individual
      A-esterase activities using paraoxon, diazoxon, and phenylacetate as substrates.
      Results were then compared to ChE activities measured after 10 s of contact with
      an environmentally realistic amount of OP, containing 1% oxon. Both ChE
      activities were significantly inhibited, with capillary values being
      significantly more inhibited than their venous counterparts. However, no
      protective effect could be associated between the degree of A-esterase activity
      and the subsequent level of ChE inhibition observed in an individual's blood.
      These results suggest that (1) if there is any uncertainty about OP skin
      contamination, venous blood would be a more appropriate specimen to employ when
      using field ChE biomonitoring kits--it is collected in larger volumes and has
      essentially no direct contact to dermal surfaces; and (2) A-esterase activity
      demonstrates no protective effect against ChE inhibition upon a blood droplet's
      brief contact with an OP residue containing traces of oxon.

PMID- 9169061
TI  - Comparative toxicity of polychlorinated biphenyls to Japanese quail (Coturnix c.
      japonica) and American kestrels (Falco sparverius).
AB  - Polychlorinated biphenyls (PCBs) and related halogenated hydrocarbons
      bioaccumulate to high concentrations in top predators, such as raptorial birds,
      yet little is known of PCB toxicity to such species. This study explored several
      aspects of both the acute and chronic response of American kestrels (Falco
      sparverius) to three purified PCB congeners and a commercial mixture, Aroclor
      1254, and compared the response to that of the Japanese quail (Coturnix c.
      japonica), a more studied species known to be PCB sensitive. In one experiment,
      adult female birds were given single oral doses of either Aroclor 1254, 3,3',4,4'
      TCB (PCB 77, IUPAC nomenclature), 3,3',4,4',5-PCB (PCB 126) or 2,2',4,4',5,5'-HCB
      (PCB 153) and sacrificed after 5 d. In kestrels, neither the pure compounds nor
      the mixture affected hepatic or renal porphyrin levels. There was slight but
      significant hepatic and renal ethoxyresorufin O-deethylase (EROD) induction in
      birds dosed with PCBs 77 and 126. A cytochrome P-4501A (CYP1A) cross-reactive
      protein was detected in liver and kidney of kestrels given PCBs 77 and 126, but
      not in Aroclor 1254-dosed birds. In quail, an acute dose of Aroclor 1254 caused
      significant liver weight increases, hepatic and renal EROD and aminopyrine n
      demethylase (APND) induction, and dose-related hepatic and renal porphyria. Quail
      treated with PCB 126 developed hepatic and renal porphyria; EROD and APND were
      also induced. Administration of PCB 77 caused only slight induction of hepatic
      EROD activity. PCB 153 caused some hepatic and renal porphyria and induced EROD
      to the same degree as PCB 126. A hepatic CYP1A cross-reactive protein was induced
      about 200-fold in all individual quail that exhibited significant EROD induction
      and was also induced in kidney of 1 quail given Aroclor 1254. A second experiment
      examined chronic exposure to Aroclor 1254 by feeding adult females of both
      species a daily dose of 7 mg/kg/d for 4-, 8-, and 12-wk periods. There were no
      effects on hepatic porphyrins in kestrels. APND and aldrin epoxidase (AE) were
      induced; EROD was not induced, although a hepatic CYP1A-like protein was detected
      in 1 kestrel dosed for 12 wk. Chronic exposure of quail to Aroclor 1254 caused
      highly significant increases in mean hepatic porphyrin levels and in activity of
      EROD, APND, and 4-chlorobiphenyl hydroxylase; a CYP1A-like protein was also
      induced about 200-fold. In both studies, Aroclor 1254 residues accumulated in
      tissues of both species, but there was no significant relationship between
      residue levels and effects. In conclusion, adult American kestrels were
      relatively insensitive to the effects of PCBs, from both acute and chronic
      exposure, on hepatic and renal porphyrin levels. Although concentrations of a
      CYP1A-like protein were increased in some kestrels given PCBs, EROD activity was
      only marginally increased, suggesting that catalytic activity of this protein
      differed among the two species.

PMID- 9169062
TI  - Interaction of ozone exposure with airway hyperresponsiveness and inflammation
      induced by trimellitic anhydride in sensitized guinea pigs.
AB  - The effect of prior ozone (O3) exposure on airway hyperresponsiveness and
      inflammation induced by trimellitic anhydride (TMA) has been investigated in TMA
      sensitized guinea pigs. Airway responsiveness was measured as the concentration
      of acetylcholine needed to increase baseline lung resistance (RL) by 300%
      (PC300). Ozone (3 ppm for 3 h) caused an increase in -log PC300 at 1 h after
      exposure, with return of -log PC300 to control levels at 8 h. Ozone also
      increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized
      guinea pigs at 8 h after challenge from 3.85 +/- 0.09 to 4.11 +/- 0.09. Ozone
      exposure prior to TMA challenge prevented the induction of airway
      hyperresponsiveness with a mean -log PC300 of 3.51 +/- 0.20, which was not
      different from that of control TMA-sensitized group. Baseline RL was
      significantly higher in ozone-pretreated animals after TMA challenge when
      compared to those of either control or challenged with TMA alone. Ozone had no
      effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude
      that a single exposure to ozone inhibits the increase in airway responsiveness
      but increases the bronchoconstrictor response induced by TMA in TMA-sensitized
      guinea pigs; however, the inflammatory airway response to TMA is unchanged by
      preexposure to ozone.

PMID- 9169063
TI  - Effect of furazolidone on sister-chromatid exchanges, cell proliferation
      kinetics, and mitotic index in vivo and in vitro.
AB  - Furazolidone is an antimicrobial compound used in human and veterinary medicine.
      The aim of this investigation was to determine its genotoxic capacity in vitro
      and in vivo. We used the human lymphocyte culture system to detect the effect of
      2.0, 4.0, 6.0, 8.0, or 10.0 micrograms/ml, and the mouse bone marrow assay to
      determine the effect of 8.6, 30.0, or 75.0 mg/kg furazolidone. In both systems we
      determined the frequency of sister-chromatid exchanges (SCE), the cell
      proliferation kinetics (CPK), and the mitotic index (MI). The in vitro results
      showed a significant SCE increase starting from the second dose tested and a CPK
      and MI decrease starting from the third dose. The in vivo results showed a SCE
      increase with the two high doses tested, but no significant modification was
      found in the CPK and MI with the three doses tested in the experiment.

PMID- 9169064
TI  - Furan-mediated uncoupling of hepatic oxidative phosphorylation in Fischer-344
      rats: an early event in cell death.
AB  - Furan is a potent rodent hepatotoxicant and carcinogen. The present study was
      done to examine the effects of furan on hepatic energy metabolism both in vivo
      and in vitro in male F-344 rats. Furan produced concentration- and incubation
      time-dependent irreversible reductions in ATP in freshly isolated F-344 rat
      hepatocytes. Furan-mediated depletion of ATP occurred prior to cell death and was
      prevented by including 1-phenylimidazole, a cytochrome P450 inhibitor, in the
      suspensions. Male F-344 rats were treated with furan (0-30 mg/kg, po) and killed
      24 hr later to prepare hepatic mitochondria. Furan produced dose-dependent
      increases in state 4 respiration and ATPase activity. Both of these changes were
      prevented by 1-phenylimidazole cotreatment. In a separate series of experiments,
      mitochondria were prepared from isolated rat hepatocytes following incubation
      with furan (2-100 microM) for 1-4 hr. Furan produced incubation time- and
      concentration-dependent increases in state 4 respiration and ATPase activity.
      Furan-mediated mitochondrial changes were prevented by adding 1-phenylimidazole
      to the hepatocyte suspensions. These results indicate that the ene-dialdehyde
      metabolite of furan uncouples hepatic oxidative phosphorylation in vivo and in
      vitro. In vitro studies using an isolated hepatocyte suspension/culture system
      demonstrated that the concentration response for furan-mediated mitochondrial
      changes in suspension corresponded with the concentration responses for cell
      death after 24 hr. Including 1-phenylimidazole or oligomycin plus fructose in
      hepatocyte suspensions prevented furan-induced cell death after 24 hr in culture.
      The results of this study indicate that furan-induced uncoupling of oxidative
      phosphorylation is an early, critical event in cytolethality both in vivo and in
      vitro.

PMID- 9169065
TI  - Hexachlorobenzene-induced immunomodulation and skin and lung lesions: a
      comparison between brown Norway, Lewis, and Wistar rats.
AB  - Strain dependence of the induction of skin and lung lesions by hexachlorobenzene
      (HCB) in the rat was studied to further the insight into the etiology of the
      lesions. To this end, 3- to 4-week-old female Brown Norway (BN), Lewis, and
      Wistar rats received diets supplemented with 150 mg (BN and Lewis), 450 mg (BN,
      Lewis, and Wistar) or 900 mg (BN and Wistar) HCB per kilogram diet for 4 weeks.
      Gross skin lesion development during exposure as well as pathologic changes in
      skin and lungs and various parameters of immunomodulation after exposure were
      assessed. General toxicity as judged by a slight increase in body weight gain and
      induction of liver cell hypertrophy was similar in BN and Lewis rats exposed to
      450 mg/kg HCB and in Wistar rats exposed to 900 mg/kg HCB. Skin lesions ranged
      from redness to large exudating sores with crusts. With regard to dose, time of
      onset, incidence, and severity, skin lesions were very severe in BN, moderate in
      Lewis, and negligible in Wistar. Porphyrins could not be detected in the skin,
      whereas porphyrins in the liver were seen only in Lewis rats. Histology showed
      epidermal hyperplasia, deep dermal venules with activated endothelium, and deep
      dermal inflammatory infiltrates mainly consisting of eosinophilic granulocytes in
      BN and of mononuclear cells in Lewis and Wistar. Nonlesional skin of HCB-exposed
      rats showed very similar, though less prominent, changes. Lung pathology appeared
      negligibly strain-dependent; histology showed venules with an activated
      endothelium surrounded by a perivascular infiltrate as well as focal alveolar
      macrophage accumulations in all strains. Parameters of immunomodulation showed
      moderate strain dependence; relative spleen weights were dose-dependently
      increased in BN and Wistar and in the 450 mg/kg group in Lewis rats. BN rats
      showed a more marked splenomegaly than the other strains. Relative popliteal
      lymph node weights were increased significantly in BN and Lewis rats exposed to
      450 mg/kg HCB. In all strains, HCB increased lymph node HEVs. Serum IgE and IgG
      levels were increased significantly in a dose-dependent way in BN rats only.
      Total serum IgM levels were elevated significantly in BN, Lewis, and Wistar rats
      that received 450 mg/kg and in Wistar rats that received 900 mg/kg HCB. Serum IgM
      levels against ssDNA were dose-dependently increased in all strains, being more
      marked in BN and Lewis than in Wistar rats. It is concluded that the HCB-induced
      inflammatory skin and lung pathologies have different etiology. Pronounced strain
      differences in the skin lesions suggest a specific involvement of the immune
      system. Skin lesions correlated significantly with all assessed parameters of
      immunomodulation in BN, with some in Lewis and with none in Wistar rats. No
      correlation was observed between the parameters of immunomodulation and lung
      lesions.

PMID- 9169066
TI  - Induction of liver-associated transforming growth factor beta 1 (TGF-beta 1) mRNA
      expression by carbon tetrachloride leads to the inhibition of T helper 2 cell
      associated lymphokines.
AB  - Acute treatment of B6C3F1 mice with a hepatotoxic dose (500 mg/kg) of carbon
      tetrachloride (CCl4) produced a marked but transient increase in transforming
      growth factor beta 1 (TGF-beta 1) mRNA expression in the liver within 24 hr. We
      have previously shown that an identical dose of CCl4 also produces a marked
      increase in serum TGF-beta 1 concentrations which peak at 48 hr and produce a
      marked inhibition of the anti-sRBC IgM antibody forming cell (AFC) response.
      Similar increases in TGF-beta 1 transcripts scripts in the liver were also
      induced by an acute hepatotoxic dose (600 mg/kg) of acetaminophen. No increase in
      TGF-beta 1 mRNA expression was detected in the spleen following treatment with
      either agent. Direct addition of TGF-beta 1 (0.05-1.0 ng/ml) to naive splenocyte
      cultures produced a marked and dose-related inhibition of the anti-sRBC IgM AFC
      response. Under the same conditions, TGF-beta 1 induced a marked decrease in IL-4
      and IL-5 mRNA expression in sRBC-sensitized splenocytes. Concomitantly, TGF-beta
      1 induced a rapid increase in NF-kappa B/Rel trans-acting factor binding within
      the first 24 hr post-sRBC sensitization of splenocytes. Conversely, NF-kappa
      B/Rel binding activity was inhibited on Days 2 through 4 in sRBC-sensitized
      splenocytes in the presence of TGF-beta 1. The increase in NF-kappa B/Rel binding
      within 24 hr following sRBC sensitization is consistent with the positive
      influence TGF-beta 1 exerts on Th1 cytokines such as IL-2 and IFN-gamma.
      Conversely the decrease in NF-kappa B/Rel binding at the later time period during
      the AFC response (Days 2-4) coincides with the inhibitory effects TGF-beta 1
      exerted on IgM production by B cells.

PMID- 9169067
TI  - In vitro metabolism of 4-vinylcyclohexene in rat and mouse liver, lung, and
      ovary.
AB  - 4-Vinylcyclohexene (4-VCH), the dimer of 1,3-butadiene, is an ovarian toxicant in
      mice due to the formation of a diepoxide metabolite, but the tissue-specific site
      of formation of the metabolites is unknown. Microsomal preparations from liver,
      lung, and ovaries obtained from female Crl:CD BR rats and female B6C3F1 mice were
      tested for their ability to metabolize the following reactions: 4-VCH to 4-VCH
      1,2-epoxide and 4-VCH-7,8-epoxide; 4-VCH-1,2-epoxide to 4-VCH diepoxide and 4-VCH
      1,2-diol; 4-VCH-7,8-epoxide to 4-VCH diepoxide and 4-VCH-7,8-diol; and hydrolysis
      of 4-VCH diepoxide. Microsomes were incubated with the test chemical and the
      reaction products were analyzed by gas chromatography. Rat liver and lung
      microsomes and mouse liver and lung microsomes metabolized 4-VCH to 4-VCH-1,2
      epoxide at detectable rates. Mouse liver had a Vmax for the reaction that was 56
      fold higher than that for rat liver (11.1 and 0.20 nmol/min/mg protein,
      respectively). The Vmax for mouse lung was 2-fold higher than that for rat lung.
      4-VCH-1,2-epoxide formation was not detected in ovarian microsomes from rats or
      mice. Metabolism of 4-VCH to 4-VCH-7,8-epoxide was detected in microsomes from
      rat liver and mouse liver and lung, at rates very low compared to those for
      metabolism to the 1,2-epoxide. Rat and mouse liver had very similar K(m) and Vmax
      values for metabolism of 4-VCH-1,2-epoxide to 4-VCH diepoxide. The Vmax for rat
      liver was 3.69 and for mouse liver was 5.35 nmol/min/mg protein. Rat and mouse
      ovaries did not have detectable capacity to metabolize 4-VCH-1,2-epoxide to the
      diepoxide. Rat and mouse liver and lung have very similar K(m) and Vmax values
      for metabolism of 4-VCH-7,8-epoxide to the diepoxide, while ovaries did not have
      detectable rates for this reaction. Hydrolysis of 4-VCH-1,2-epoxide to 4-VCH-1,2
      diol was at similar rates in rat and mouse liver microsomes. Hydrolysis of 4-VCH
      7,8-epoxide to 4-VCH-7,8-diol was detected only in rat liver microsomes.
      Hydrolysis of 4-VCH diepoxide was detected in rat and mouse liver and lung, and
      in rat ovary microsomes. The Vmax for rat liver was 9-fold greater than that for
      mouse liver (5.51 and 0.63 nmol/min/mg protein, respectively), and lung and ovary
      tissues were not as active as rat liver. The balance of activation versus
      detoxication reactions in rats and mice suggests that the mouse may be more
      susceptible to 4-VCH toxicity because of generation of high levels of epoxide
      metabolites. In general, the mouse is more efficient at metabolism of 4-VCH to
      epoxides than is the rat. In contrast, the rat may be more efficient at
      hydrolysis of epoxides. Thus, the rat would tend to produce a lower concentration
      of epoxide metabolites than the mouse, at equal doses of 4-VCH.

PMID- 9169068
TI  - Methylation of the NMDA receptor agonist L-trans-2,3-pyrrolidine-dicarboxylate:
      enhanced excitotoxic potency and selectivity.
AB  - This study investigated the excitotoxic properties of a novel series of NMDA
      analogues in which a methyl group was introduced to the 5-position of the
      pyrrolidine ring of L-trans-2,3-PDC, a previously identified NMDA receptor
      agonist. While all of these compounds induced NMDA-receptor-mediated injury,
      methylation increased in vivo excitotoxic potency 1000-fold. Injections (1 mu 1)
      in rat dorsal hippocampus of cis- and trans-5-methyl-L-trans-2,3-PDC (0.1 nmol)
      induced 50-70% neuronal damage to areas CA1 and CA4, comparable to that induced
      by 100 nmol of L-trans-2,3-PDC. Further, cis- and trans-methylated analogues
      induced distinct patterns of hippocampal pathology consistent with differential
      excitotoxic vulnerability of neurons expressing NMDA receptors. Neuronal damage
      produced by the 5-methyl-L-trans-2,3-PDCs could be blocked by coadministration of
      MK-801 (3 mg/kg ip), but not NBQX (25 nmol). Biochemical and physiological assays
      confirmed the action of the analogues as NMDA agonists, but did not provide an
      explanation for differences in excitotoxic potency between the methylated and
      nonmethylated 2,3-PDCs. or example, the activity of the compounds as inhibitors
      of 3H-glutamate binding (IC50 values: 0.4, 1.4, and 1.2 microM for cis-5-methyl
      ,trans-5-methyl-, and L-trans-2,3-PDC, respectively), agonists at NR1A/NR2B
      receptors (EC50 values: 5, 49, and 16 microM for cis-5-methyl-,trans-5-methyl-,
      and L-trans-2,3-PDC, respectively), and in vitro excitotoxins in cortical
      cultures varied only two- to fivefold as a consequence of methylation. Potential
      roles of NMDA receptor subtypes and transport in these effects are discussed. As
      potent and selective NMDA excitotoxins, cis- and trans-5-methyl-L-trans-2,3-PDC
      will be of value studying excitotoxic mechanisms, MDA-receptor-mediated
      pathology, and NMDA receptor heterogeneity.

PMID- 9169069
TI  - Disposition of netobimin, albendazole, and its metabolites in the pregnant rat:
      developmental toxicity.
AB  - Netobimin (NTB), a benzimidazole prodrug with a good anthelmintic spectrum, was
      administered orally to female rats at a dose of 59.5 mg NTB/kg, to study its
      pharmacokinetic behavior and the disposition of its most important metabolites,
      albendazole (ABZ), albendazole sulfoxide (ABZSO), and albendazole sulfone
      (ABZSO2). ABZ was found in plasma after 6 hr. Peak plasma concentrations (Cmax)
      and areas under curves (AUC) of ABZSO were eight- and fourfold higher,
      respectively, than those of ABZSO2. To study NTB disposition in pregnant rats,
      three different drug doses (50, 59.5, and 70.7 mg/kg) were given. No significant
      differences were found between plasma concentrations for each metabolite at the
      three doses studied. Only ABZ concentrations rose slightly as dose increased.
      ABZ, ABZSO, and ABZSO2 were found in amniotic sacs and embryos at concentrations
      that were higher than plasma at the same times. The fetuses obtained after
      administration of each of the doses of NTB were studied to detect developmental
      toxicity. A significant correlation was found between rate of developmental
      toxicity and metabolite concentration. ABZSO embryo concentrations could be the
      main factor accounting for toxicity.

PMID- 9169070
TI  - Depletion of glutathione by benzo(a)pyrene metabolites, ionomycin, thapsigargin,
      and phorbol myristate in human peripheral blood mononuclear cells.
AB  - Previous studies in this laboratory have shown that polycyclic aromatic
      hydrocarbons (PAHs) alter Ca2+ homeostasis and inhibit activation of both B and T
      lymphocytes obtained from rodents and humans. In the present studies, we
      demonstrate that alpha-naphthoflavone (ANF), an inhibitor of cytochrome P4501A
      activity, reduced the Ca2+ elevation produced by BaP in human peripheral blood
      mononuclear cell (HPBMC) lymphocytes. These results suggested that BaP
      metabolites may play a role in intracellular Ca2+ homeostasis in human
      lymphocytes. Reactive oxidative intermediates of BaP produced in HPMBC are known
      to be highly carcinogenic and have also been shown to be immunosuppressive. We
      examined the effects of benzo(a)pyrene (BaP), 7,12-dimethylbenz(a)anthracene
      (DMBA), benzo(e)pyrene (BeP), and anthracene, as well as certain BaP metabolites,
      on the levels of intracellular Ca2+ and glutathione in HPBMC. While BaP, DMBA,
      BeP, and anthracene did not cause a statistically significant decrease in GSH in
      HPBMC at concentrations of 1 or 10 microM following a 6-, 48-, or 72-hr exposure,
      reactive BaP metabolites including 4,5-epoxide BaP and 7,8-diol-9,10-epoxide BaP
      consistently produced a 20-30% depletion of glutathione in HPBMC following a 6-hr
      treatment period. These BaP metabolites also elevated intracellular Ca2+ in HPBMC
      during a 6-hr incubation. Results of these experiments suggest that metabolism of
      BaP to certain epoxide metabolites may be responsible for sulfhydryl damage
      leading to transient GSH depletion and Ca2+ elevation. These results are
      consistent with the hypothesis that sulfhydryl damage by certain PAH metabolites
      may lead to altered Ca2+ homeostasis, leading to inhibition of cell activation
      and proliferation in HPBMC.

PMID- 9169071
TI  - Effects of cadmium on electrolyte ions in cultured rat hepatocytes studied by X
      ray microanalysis of cryosections.
AB  - The distribution of elements in isolated and cultured rat hepatocytes was
      measured by energy dispersive electron probe X-ray microanalysis of freeze-dried
      ultrathin cryosections. The intracellular compartmentation of electrolyte ions,
      in particular the content of sodium, chloride, and potassium, was found to depend
      on culture conditions and on the amount of cadmium chloride added to the culture
      medium. In cells exposed to 1-10 microM cadmium without carbon dioxide supply,
      the potassium/sodium ratio decreased from control values of about 10 to values
      below 1 within 30 min. Changes of potassium and sodium content were followed by
      an increase in the intracellular chloride content. In cells exposed to 1-10
      microM cadmium with carbon dioxide supply, changes of the electrolyte composition
      were delayed to 1-2 days. An increase of intracellular chloride preceded the
      inversion of the intracellular potassium/sodium ratio. High cadmium doses induced
      a cytoplasmic calcium increase and finally disintegration and decay of cell
      structure. Almost normal potassium and sodium contents were found in cells
      exposed to 10 microM cadmium in the presence of 100 microM zinc with carbon
      dioxide for 1 day. Changes in the intracellular electrolyte composition by
      adverse or toxic conditions were detected before any structural damage became
      visible. Thus, energy dispersive electron probe X-ray microanalysis of
      cryosections proved to be a sensitive probe of cell viability and cytotoxicity.

PMID- 9169072
TI  - Bacterial endotoxin enhances the hepatotoxicity of allyl alcohol.
AB  - Lipopolysaccharide (LPS), or bacterial endotoxin, causes liver damage at
      relatively large doses in rats. Smaller doses, however, may influence the
      response to other hepatotoxicants. The purpose these studies was to examine the
      effect of exposure to relatively all doses of LPS on the hepatotoxic response to
      allyl alcohol, which causes periportal necrosis in laboratory rodents through an
      known mechanism. Rats were pretreated with LPS (100 micrograms/kg) 2 hr before
      treatment with a minimally toxic dose of allyl alcohol mg/kg), and liver toxicity
      was assessed 18 hr later from activity of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) in plasma and from histologic changes in liver
      sections. Plasma ALT and AST activities were not elevated significantly in rats
      treated with vehicle, LPS, or allyl alcohol alone, but pronounced increases were
      observed in rats treated with LPS and allyl alcohol. Significant liver injury
      occurred as early as 2 hr after allyl alcohol treatment in LPS-pretreated rats
      and peaked at 6 hr. LPS treatment did not affect the activity of alcohol
      dehydrogenase and did not affect the rate of production of NADH in isolated
      livers perfused with allyl alcohol; thus, LPS does not appear to increase the
      metabolic bioactivation of allyl alcohol into acrolein. On the other hand,
      pretreatment with 4-methylpyrazole, an inhibitor of alcohol dehydrogenase,
      abolished the hepatotoxicity of allyl alcohol in LPS-treated rats, indicating
      that production of acrolein was needed for LPS enhancement of the toxicity of
      allyl alcohol. Pretreatment of rats with gadolinium chloride (10 mg/kg), a known
      inactivator of Kupffer cell phagocytic function, decreased LPS augmentation of
      the response to allyl alcohol. These data indicate that LPS markedly enhances the
      hepatotoxic response to allyl alcohol. Furthermore, the results suggest that the
      LPS-induced enhancement of allyl alcohol hepatotoxicity occurs through a Kupffer
      cell-dependent mechanism.

PMID- 9169073
TI  - Aflatoxin B1 activation in human lung.
AB  - Inhalation exposure to the carcinogen aflatoxin B1 (AFB1) in certain occupations
      is considerable. Because circumstantial epidemiological evidence suggests that
      AFB1 inhalation may cause primary lung cancer, we investigated AFB1 activation by
      human lung microsomes. Microsomes were incubated with [3H]AFB1 (124 microM), and
      activation to the AFB1-8,9-epoxide was measured as the AFB1-glutathione (AFB1
      GSH) conjugate by HPLC. The formation of AFB1-GSH was in the range of 0.05-0.073
      fmol/mg protein/min. The role of cytochrome P450 (CYP) 3A in this activation was
      investigated by oxidation of nifedipine (a prototype substrate for CYP 3A), by
      immunoinhibition, and by immunoblot analysis. Nifedipine oxidation varied from
      0.2 to 19.2 pmol/mg protein/min in microsomes from different subjects, but did
      not correlate with AFB1 activation. Anti-human polyclonal CYP 3A4 IgG inhibited
      AFB1 activation. CYP 3A isoforms were immunoestimated to be in the range of 0.01
      1.90 pmol/mg protein. Neither CYP 1A2 nor associated activity was detected in the
      lung microsomes. These data indicate that human lung microsomes activate AFB1 to
      form the exo-AFB1-8,9-epoxide and that CYP(s) of the 3A subfamily may be
      responsible for this activity. The relatively low amount of AFB1 activation in
      human lung compared to that in human liver can be explained by the scarcity of
      CYP-containing cells in the lung. In situ AFB1 activation and resultant
      carcinogenic risk are distinctly possible in occupational settings where
      inhalation of AFB1-contaminated dusts occurs.

PMID- 9169074
TI  - Naphthalene cytotoxicity of differentiating Clara cells in neonatal mice.
AB  - Selective Clara cell injury produced by many bioactivated lung toxicants is
      thought to result from high levels of activating enzymes found in differentiated
      Clara cells. A recent study found an elevated susceptibility to the Clara cell
      toxicant 4-ipomeanol in neonatal rabbits when Clara cell P450 activity is low. To
      determine whether differentiating Clara cells in another species (mouse) are more
      susceptible to injury by a different bioactivated Clara cell toxicant
      (naphthalene), adult, 14-day postnatal (DPN) and 7DPN male mice were given a
      single intraperitoneal dose (25, 50, or 100 mg/kg) of naphthalene and killed 24
      hr later. Epithelial damage, as assessed by quantitative histopathology, included
      cellular swelling, vacuolization, and exfoliation. In 7DPN mice, bronchiolar
      epithelium was severely injured at the lowest dose of naphthalene tested, 25
      mg/kg. Bronchiolar epithelium in 14DPN mice was moderately injured at 25 mg/kg;
      injury severity was greatest at 50 and 100 mg/kg. Minimal bronchiolar epithelial
      injury occurred in adult mice at 50 mg/kg and moderate injury at 100 mg/kg. In
      proximal bronchi, epithelium of 7DPN mice showed signs of injury only at 100
      mg/kg. Bronchial epithelium of adult mice was not injured at any dose. Isolated
      distal airways from 7DPN and 14DPN mice were more sensitive to naphthalene
      exposure than isolated distal airways from adult mice. Despite the low levels of
      P450 activity, differentiating Clara cells in neonatal mice are more susceptible
      to injury by the bioactivated cytotoxicant naphthalene than are differentiated
      Clara cells in adult mice.

PMID- 9169075
TI  - Protection against methoxyacetic-acid-induced spermatocyte apoptosis with calcium
      channel blockers in cultured rat seminiferous tubules: possible mechanisms.
AB  - A calcium-mediated mechanism underlying spermatocyte apoptosis induced by 2
      methoxyethanol (2-ME) has been previously proposed. This hypothesis was tested in
      vitro in the present study using cultured juvenile (25 days old) and adult rat
      seminiferous tubules (JRST and ARST, respectively) with methoxyacetic acid (MAA,
      the active metabolite of 2-ME). In JRST, spermatocyte degeneration was
      morphologically obvious 19 hr after a 5-hr exposure to 5 mM MAA. The lesion was
      unaffected by the presence or absence of extratubular Ca2+. However, MAA-induced
      cell death was significantly prevented by cotreatment with the dihydropyridines
      (DHP) nifedipine (50 microM) and nicardipine (20 microM), as well as verapamil
      (50 microM) and TMB-8 (50 microM), all of which are able to inhibit calcium
      movement through plasma membranes. However, neither ryanodine, dantrolene, nor
      cyclosporin A and ruthenium red, which inhibit Ca2+ mobilization from
      intracellular stores (endoplasmic reticulum and mitochondria), affected the MAA
      induced cell death. Inhibition of calcium mobilization through IP3-sensitive
      pathways by blocking the product of IP3 with manoalide, neomycin, and U73122 did
      not block the MAA-induced lesion. The protective effects of 50 microM nifedipine
      and 50 microM TMB-8 were also observed in ARSTs treated with 10 mM MAA for 5 hr.
      However, when rat testicular sections were immunohistochemically stained with
      monoclonal antibodies specific for the alpha 1 (the DHP receptor) or the alpha 2
      subunits of DHP-sensitive calcium channels, no positive staining was found.
      Finally, in an attempt to see whether the intracellular free calcium
      concentrations ([Ca2+]i) in germ cells were increased after the MAA treatment,
      intact seminiferous tubules were loaded with indo-1 and were measured using laser
      scanning confocal microscopy. No detectable increase in the signal in MA A
      sensitive spermatocytes was observed, while a 34-54% increase in the signal could
      be detected in the same cell types when tubules were exposed to 10 microM of the
      calcium ionophore 4-bromo-A23187 for 5 min. Collectively, these data suggest that
      the protective effect of calcium channel blockers against the MAA-induced
      spermatocyte apoptosis is probably not through their blocking effect on DHP
      sensitive calcium channels. We postulate alternate mechanisms based on
      stabilization of cells membranes, or interactions with calmodulin or protein
      kinase C.

PMID- 9169076
TI  - Physiologically based pharmacokinetic modeling of a ternary mixture of alkyl
      benzenes in rats and humans.
AB  - The objective of the present study was to develop a physiologically based
      pharmacokinetic (PBPK) model for a ternary mixture of alkyl benzenes [toluene
      (TOL), m-xylene (XYL), and ethylbenzene (EBZ)] in rats and humans. The approach
      involved the development of the mixture PBPK model in the rat and extrapolation
      to humans by substituting rat physiological parameters and blood:air partition
      coefficients in the model with those of humans, scaling maximal velocity for
      metabolism on the basis of body weight0.75 and keeping all other model parameters
      species-invariant. The development of the PBPK model for the ternary mixture in
      the rat was accomplished by initially validating or refining the existing PBPK
      models for TOL, XYL, and EBZ and linking the individual chemical models via the
      hepatic metabolism term. Accordingly, the Michaelis-Menten equation for each
      solvent was modified to test four possible mechanisms of metabolic interaction
      (i.e., no interaction, competitive inhibition, noncompetitive inhibition, and
      uncompetitive inhibition). The metabolic inhibition constant (Ki) for each binary
      pair of alkyl benzenes was estimated by fitting the binary chemical PBPK model
      simulations to previously published data on blood concentrations of TOL, XYL, and
      EBZ in rats exposed for 4 hr to a binary combination of 100 or 200 ppm of each of
      these solvents. Competitive metabolic inhibition appeared to be the most
      plausible mechanism of interaction at relevant exposure concentrations for all
      binary mixtures of alkyl benzenes in the rat (Ki,TOL-XYL = 0.17; Ki,TOL-EBZ =
      0.79; Ki,XYL-TOL = 0.77; Ki,XYL-EBZ = 1.50; Ki,EBZ-TOL = 0.33; Ki,EBZ-XYL = 0.23
      mg/L). Incorporating the Ki values obtained with the binary chemical mixtures,
      the PBPK model for the ternary mixture simulated adequately the time course of
      the venous blood concentrations of TOL, XYL, and EBZ in rats exposed to a mixture
      containing 100 ppm each of these solvents. Following the validation of the
      ternary mixture model in the rat, it was scaled to predict the kinetics of TOL,
      XYL, and EBZ in blood and alveolar air of human volunteers exposed for 7 hr to a
      combination of 17, 33, and 33 ppm, respectively, of these solvents. Model
      simulations and experimental data obtained in humans indicated that exposure to
      atmospheric concentrations of TOL, XYL, and EBZ that remain within the
      permissible concentrations for a mixture would not result in biologically
      significant modifications of their pharmacokinetics. Overall, this study
      demonstrates the utility of PBPK models in the prediction of the kinetics of
      components of chemical mixtures, by accounting for mechanisms of binary chemical
      interactions.

PMID- 9169077
TI  - A multicompartment geometric model of the liver in relation to regional induction
      of cytochrome P450s.
AB  - A geometric, multicompartment model of the liver was developed to examine
      regional protein induction and to provide model output suitable for predicting
      the degree of induction in both the whole liver and in specific regions. The
      model was based on functional hexagonal arrays within the liver. A geometric
      representation was used to divide these functional units into five zones: a
      concentric periportal zone, a fenestrated periportal region that interconnects
      among multiple functional units, and three concentric centrilobular areas,
      referred to, respectively, as zones 1 through 5. The surface areas (and volumes
      for hexagonal cylinders) of these live zones were, respectively, 13.5, 25.2,
      33.9, 20.3, and 6.8% of the total liver. The pharmacokinetic model for induction
      had dissociation constants (Kd) and Hill constants (n) for interactions of
      transcriptional activator-ligand complexes with response elements on DNA.
      Estimates of regional induction were converted to color intensities to "paint"
      the two-dimensional liver for a visual comparison with immunohistochemical
      observations. To obtain sharp moving boundaries of induced areas with increasing
      dose (as noted in various experiments), n values in each subcompartment must be
      large. To create realistic total induction curves that are relatively smooth, the
      differences in Kd values between adjacent subcompartments must be less than
      fivefold. Because of the high n values, the low-dose induction characteristics
      predicted with the multicompartment liver model differ significantly from those
      predicted with a model that considers the liver as a single homogeneous
      compartment.

PMID- 9169078
TI  - Regional hepatic CYP1A1 and CYP1A2 induction with 2,3,7,8-tetrachlorodibenzo-p
      dioxin evaluated with a multicompartment geometric model of hepatic zonation.
AB  - A physiologically based pharmacokinetic (PBPK) model for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) was combined with a five-compartment geometric
      model of hepatic zonation to predict both total and regional induction of CYP450
      proteins within the liver. Three literature studies on TCDD pharmacokinetics and
      protein induction in female rats were analyzed. In simulating low-dose behavior
      for mRNA in whole liver and, particularly, in representing immunohistochemical
      observations, the five-compartment model was more successful than conventional
      homogeneous one-compartment liver models. The five-compartment liver model was
      used with the affinity of TCDD for the Ah receptor (AhR) held constant across all
      the liver (Kb = 0.2 nM). The presumed affinities of the AhR-TCDD complex for TCDD
      responsive elements in the CYP1A1 (Kd1) and CYP1A2 (Kd2) genes varied between
      adjacent compartments by a factor of 3. This parameterization leads to predicted
      81-fold differences in affinities between the centrilobular and the periportal
      regions. The affinities used for AhR-TCDD complex binding to TCDD response
      elements for CYP1A2 in compartment 3 (the midzonal area) ranged from 0.08 to 1.0
      nM in the three studies modeled. For CYP1A1 the corresponding dissociation
      constant in compartment 3 varied from 0.6 to 2.0 nM. In each compartment, the
      Hill coefficient for induction had to be 4 or greater to match the
      immunohistochemical results. This multi-compartment liver model is consistent
      with data on protein and mRNA induction throughout the liver and on the regional
      distribution of these proteins. No previous model has incorporated regional
      variations in induction. The PBPK analysis based on the multicompartment liver
      model suggests that the low-dose behavior for hepatic CYP1A1/CYP1A2 induction by
      TCDD is highly non-linear.

PMID- 9169079
TI  - Mercury in saliva and feces after removal of amalgam fillings.
AB  - The toxicological consequences of exposure to mercury (Hg) from dental amalgam
      fillings is a matter of debate in several countries. The purpose of this study
      was to obtain data on Hg concentrations in saliva and feces before and after
      removal of dental amalgam fillings. In addition Hg concentrations in urine,
      blood, and plasma were determined. Ten subjects had all amalgam fillings removed
      at one dental session. Before removal, the median Hg concentration in feces was
      more than 10 times higher than in samples from an amalgam free reference group
      consisting of 10 individuals (2.7 vs 0.23 mumol Hg/kg dry weight, p < 0.001). A
      considerable increase of the Hg concentration in feces 2 days after amalgam
      removal (median 280 mumol Hg/kg dry weight) was followed by a significant
      decrease. Sixty days after removal the median Hg concentration was still slightly
      higher than in samples from the reference group. In plasma, the median Hg
      concentration was 4 nmol/liter at baseline. Two days after removal the median Hg
      concentration in plasma was increased to 5 nmol/liter and declined subsequently
      to 1.3 nmol/liter by Day 60. In saliva, there was an exponential decline in the
      Hg concentration during the first 2 weeks after amalgam removal (t 1/2 = 1.8
      days). It was concluded that amalgam fillings are a significant source of Hg in
      saliva and feces. Hg levels in all media decrease considerably after amalgam
      removal. The uptake of amalgam mercury in the GI tract in conjunction with
      removal of amalgam fillings seems to be low.

PMID- 9169080
TI  - Strain differences in tissue concentrations of mercury in inbred mice treated
      with mercuric chloride.
AB  - Tissue concentrations of mercury were determined by cold vapor atomic absorption
      spectrometry in different inbred mouse strains after continuous treatment with
      HgCl2 (3 weekly sc injections of 0.5 mg/kg bw) for up to 12 weeks. Except for the
      thymus, in which steadily increasing mercury concentrations were found, in steady
      state levels of mercury were reached in blood and liver after 4 weeks and in
      spleen and kidney after 8 weeks. In the closely related strains C57BL/6, B10.D2,
      and B10.S, which differ only or primarily at the major histocompatibility
      complex, mercury concentrations in blood and liver were about twofold lower and
      renal concentrations were about three- to fivefold lower than those detected in
      strains A.SW and DBA/2. Another strain difference was observed in the spleen:
      after 8 and 12 weeks of continuous HgCl2 treatment, mercury concentrations in the
      spleen of strains A.SW, C57BL/6, and B10.S were significantly higher than those
      in strains DBA/2 and B10.D2. The strain difference in the spleen, an organ of the
      immune system, correlates with the susceptibility to the HgCl2-induced systemic
      autoimmune syndrome in mice in that the strains showing a higher mercury
      accumulation in the spleen are susceptible to this form of chemically induced
      autoimmunity, whereas the strains with lower mercury concentrations in the spleen
      are resistant.

PMID- 9169081
TI  - Cadmium inhibits DNA strand break rejoining in methyl methanesulfonate-treated
      CHO-K1 cells.
AB  - The cogenotoxicity of Cd has been recognized. This effect may stem from Cd
      inhibition of DNA repair. We studied the effects of Cd on DNA repair of methyl
      methanesulfonate (MMS)-damaged Chinese hamster ovary cells (CHO-K1) by single
      cell alkaline electrophoresis. The results indicate that in the presence of Cd,
      DNA strand breaks accumulated in MMS-treated cells. Using hydroxyurea (Hu) plus
      cytosine-beta-D-arabinofuranoside (AraC) to block DNA polymerization, DNA strand
      breaks accumulated and Cd had little inhibitory effects on these accumulations.
      However, Cd inhibited the rejoining of these DNA strand breaks, which could be
      rejoined 6 hr after release from Hu plus AraC blockage. These results indicate
      that the potency of Cd inhibition of DNA repair replication and/or ligation may
      be greater than the inhibition of DNA adduct excision. To further elucidate this
      mechanism, we used an in vitro cell-free assay system to analyze the Cd effects
      on DNA repair synthesis, DNA polymerization, and DNA ligation. We have shown a
      dose-dependent inhibition of these three activities by Cd in CHO-K1 cell extract.
      The IC50s of Cd were 55, 26, and 10 microM, respectively. Moreover, Cd inhibition
      of DNA ligation in cell extract could be recovered partially by thiol compounds
      such as glutathione, beta-mercaptoethanol, dithiothreitol, and metallothionein.
      Since both in vivo and in vitro studies demonstrated that Cd was more effectively
      involved in interfering with the DNA ligation step and that thiol agents could
      partially remove Cd inhibition of DNA ligation, we speculate that part of the Cd
      inhibition of DNA repair may be through binding of Cd to the proteins
      participating in DNA ligation.

PMID- 9169082
TI  - Carbaryl induces CYP1A1 gene expression in HepG2 and HaCaT cells but is not a
      ligand of the human hepatic Ah receptor.
AB  - In spite of increasing numbers of insecticides used in agriculture, there are
      serious concerns regarding the potential risks of exposure to these agents.
      Carbaryl is one of the most important carbamate insecticides and has been used
      for about 30 years to control a wide range of pests. The study was designed to
      investigate if, among various insecticides currently used in world agriculture,
      this compound could induce human CYP1A1, an enzyme known to play an important
      role in the chemical activation of xenobiotics to genotoxic derivatives. Studies
      on HepG2 and HaCaT cell lines showed that carbaryl is capable of increasing, in a
      dose-dependent manner, both the ethoxyresorufin rufin-O-dec, O-deethylase
      activity and the steady-state concentrations of CYP1A1 mRNA, suggesting a
      transcriptional activation of this gene. When alpha-naphthoflavone, a partial Ah
      receptor (AhR) antagonist, and 8-methoxypsoralen, which interferes with the
      binding of activated AhR to the xenobiotic responsive element (XRE), were added
      to the cultures, CYP1A1 induction was suppressed. However, competitive binding
      studies using the 9S enriched fraction of human cytosol indicated that carbaryl
      did not displace [3H]TCDD from AhR. These data, together with the activation of a
      XRE-directed CAT reporter gene by carbaryl, suggest that induction of CYP1A1
      involves the participation of the AhR and the XRE, but is not mediated by a
      direct carbaryl-receptor interaction. An alternative ligand-independent mechanism
      should be considered. Therefore, although carbaryl concentration in food is very
      low, care should be taken because of its possible adverse effects in human health
      through liver and skin, given the well established toxicological importance of
      CYP1A1 induction.

PMID- 9169083
TI  - Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella
      typhimurium: contrasting results with bromodichloromethane off chloroform.
AB  - Trihalomethanes (THMs) are the most prevalent disinfection by-products identified
      in chlorinated drinking water. Among the THMs, chloroform (CHCl3) generally
      occurs at the highest concentration in finished water, but the concentrations of
      each of the brominated THMs (CHBrCl2, CHBr2Cl, and CHBr3) can exceed that of
      CHCl3. Each of these four THMs was carcinogenic in rodents in chronic oral dosing
      studies. This study assessed THM mutagenicity in a strain of Salmonella
      typhimurium TA1535 that was transfected with rat theta-class glutathione S
      transferase T1-1 (+GST). The +GST strain and its nontransfected parent strain (
      GST) were employed in a plate-incorporation assay and exposed for 24 hr to the
      vapor of individual THMs at concentrations up to 25,600 ppm in sealed Tedlar
      bags. Base-substitution revertants were produced in the +GST strain in a dose
      dependent fashion by CHBrCl2 but not by CHCl3. At 4800 ppm CHBrCl2, which
      produced a calculated agar concentration of 0.67 mM, there were 419 +/- 75
      revertants per plate compared to a spontaneous level of 23 +/- 5. CHCl3 produced
      a doubling of revertants only at the two highest concentrations tested (19,200
      and 25,600 ppm). These results indicate that bromination of THMs confers the
      capability for theta-class GST-mediated transformation to mutagenic intermediates
      at low substrate concentrations, suggesting the possibility of a similar
      activation route in humans. Further, the very low affinity of the GSH-dependent
      pathway for CHCl3 demonstrates that different THMs can induce adverse effects via
      different mechanisms, indicating that risk evaluations of THMs should not treat
      members of this class as if they shared a common mode of action.

PMID- 9169084
TI  - A hexameric phosphorothioate oligonucleotide telomerase inhibitor arrests growth
      of Burkitt's lymphoma cells in vitro and in vivo.
AB  - A phosphorothioate oligonucleotide (PS-ODN) with sequence identical to the repeat
      sequence of the mammalian telomere, 5'-d(TTAGGG)-3', was incubated with a
      Burkitt's lymphoma-derived (OMA-BL1) cell line. This hexanucleotide inhibits
      telomerase activity in cell lysates, lengthens cell doubling time, and induces
      apoptosis. Concatenated repeats (12-, 18-, and 24-mers) of the 5'-d(TTAGGG)-3'
      motif induce similar cellular responses. Scrambled sequences do not efficiently
      inhibit telomerase activity or significantly alter cell growth and viability. The
      in vivo efficacy of this PS-ODN was evaluated in a xenograft human-nude mouse
      model. Once tumors were established these animals were administered the telomere
      mimic, 5'-d(TTAGGG)-3', a control scrambled sequence 5'-d(TGTGAG)-3', or saline
      for 14 days via a subcutaneous osmotic pumps in a blinded study monitoring tumor
      size with dose and time. A significant decrease in tumor size was observed in
      animals given 50 micrograms/mouse/day 5'-d(TTAGGG)-3', but not following 5'
      d(TGTGAG)-3', relative to the saline-treated animals. The antitumor activity of
      the 6-mer telomere mimic demonstrated a dose dependency including a reduction in
      metastatic nodules in the spleen. No activity was observed with the scrambled
      controls. In addition to antitumor activity we observed an increase in the mouse
      hematopoietic progenitor cell populations, BFU-e and CFU-GM. These results
      demonstrated the effects of a short hexameric oligonucleotide telomere mimic in
      vitro and in vivo and the potential utility of short oligonucleotides as
      telomerase inhibitors.

PMID- 9169085
TI  - Definitive evidence for the acute sarin poisoning diagnosis in the Tokyo subway.
AB  - A new method was developed to detect sarin hydrolysis products from erythrocytes
      of four victims of sarin (isopropylmethylphosphonofluoridate) poisoning resulting
      from the terrorist attack on the Tokyo subway. Sarin-bound acetylcholinesterase
      (AChE) was solubilized from erythrocyte membranes of sarin victims, digested with
      trypsin, the sarin hydrolysis products bound to AChE were released by alkaline
      phosphatase digestion, and the digested sarin hydrolysis products were subjected
      to trimethylsilyl derivatization and detected by gas chromatography-mass
      spectrometry. Isopropylmethylphosphonic acid, which is a sarin hydrolysis
      product, was detected in all sarin poisoning, victims we examined and
      methylphosphonic acid, which is a sarin and soman hydrolysis product, was
      determined in all victims. Postmortem examinations revealed no macroscopic and
      microscopic findings specific to sarin poisoning and sarin and its hydrolysis
      products were almost undetectable in their blood. We think that the procedure
      described below will be useful for the forensic diagnosis of acute sarin
      poisoning.

PMID- 9169086
TI  - Decreased transthyretin (TTR) concentrations in the cerebrospinal fluid after
      lead exposure.

PMID- 9169087
TI  - Developmental expression of morphoregulatory genes in the mouse embryo: an
      analytical approach using a novel technology.
AB  - The molecular techniques of in situ transcription and antisense RNA amplification
      (IST/aRNA) have allowed for the monitoring of coordinate changes in the
      expression of multiple genes simultaneously. However, the analysis of their
      concurrent behavior during murine embryogenesis has been problematic. Studies
      involving the investigation of temporal and spatial gene expression during
      embryogenesis have focused solely on the analysis of isolated, single gene
      events. Such an approach has failed to provide an integrative picture of genetic
      control over the varied and complicated cellular processes governing
      embryogenesis. In order to interpret the enormous amount of gene expression data
      generated by these procedures, we have attempted to develop an analytical
      framework by employing the statistical concepts of principal components analysis
      (PCA). For the current study, we performed IST/aRNA on neural tubes dissected
      from the highly inbred LM/Bc murine strain collected during four gestational time
      periods. A subset of these genes, representing a partial signaling pathway in the
      developing neuroepithelium, was then subjected to PCA. Here, we report that PCA
      highlighted the transcriptional interplay among the genes p53, wee-1, Tgf beta-2,
      and bcl-2 such that the combined reciprocal regulation of their gene products is
      suggestive of a predominant proliferative state for the developing
      neuroepithelium. The application of PCA to the gene expression data has
      elucidated previously unknown interrelationships among cell cycle genes, growth,
      and transcription factors on a transcriptional level during critical stages of
      neurulation. The information gleaned from this analysis, while not definitive,
      suggests distinct hypotheses to guide future research.

PMID- 9169088
TI  - The relationship of genotype to phenotype in phenylalanine hydroxylase
      deficiency.
AB  - Seventy-two adults with phenylketonuria were evaluated to investigate the
      genotypic relationship to phenotype. Patient data were collected by chart review
      and medical follow-up as well as current psychological evaluation. Nineteen
      diagnosed neonatally had remained on a phenylalanine-restricted diet all their
      lives, whereas 34 who were also diagnosed on newborn screening had discontinued
      dietary restriction during childhood. Nineteen others who were born prior to
      newborn screening were diagnosed later than the newborn period on clinical
      grounds but have remained on dietary restriction. Comparison between intellectual
      ability, academic achievement, and mental illness was made with degree of diet
      control as defined by range of blood phenylalanine levels over time. Diet
      discontinuation in childhood did not significantly lower IQ per se but appeared
      to diminish academic achievement. The lowest IQ scores were associated with poor
      dietary restriction of phenylalanine in the diet during childhood. While there
      appears to be a strong genotypic relationship to phenotypic metabolic parameters
      in phenylketonuria, there does not seem to be a similar relationship to
      intellectual ability in adults. Mutation R408W was not strongly related to the
      occurrence of mental illness in this sample. We conclude that dietary restriction
      of phenylalanine neonatally and good control contributed to normal intellectual
      development. Continuation of dietary treatment into adulthood appeared to improve
      academic achievement in patients with severe phenylalanine hydroxylase mutations.

PMID- 9169089
TI  - Highly conserved asparagine in the basic domain of Myc is dispensable for DNA
      binding, transformation, and apoptosis.
AB  - The basic region of c-Myc and other basic helix-loop-helix (b-HLH)-containing
      proteins bind to the palindromic DNA sequences CANNTG. For the myogenic factor
      MyoD, a member of the b-HLH family, mutation of several basic region residues
      abrogates muscle differentiation, but not DNA binding. One of the amino acid
      positions displaying this behavior in MyoD aligns with a highly conserved
      asparagine in Myc. This conserved asparagine displays complete tolerance for
      alanine substitution as measured by DNA binding. To test the possibility of
      whether the basic region of Myc encodes a second biological function, the
      conserved asparagine in c-Myc (N360) was mutated to alanine and tested for the
      Myc-dependent functions of cellular transformation and apoptosis. In contrast to
      the deleterious effects of such mutations in MyoD, the alanine mutant functions
      normally for both Myc-dependent cellular transformation and apoptosis induction.
      Therefore, a basic region function distinct from DNA binding may not be a general
      feature of HLH transcription factors.

PMID- 9169090
TI  - Decreased C-MYC and BCL2 expression correlates with methylprednisolone-mediated
      inhibition of Raji lymphoma growth.
AB  - Methylprednisolone (MP) and related corticosteroids are a fundamental part of
      regimens used to treat lymphoma and leukemia. In many of these malignancies,
      oncogenic activation of C-MYC and BCL2 is seen. Abnormalities of the tumor
      suppressor p53, which exerts growth-suppressing and apoptosis-enhancing functions
      through the transcriptional regulation of downstream genes including CDKN1,
      GADD45, and BCL2, are also often found. The goal was to determine the modulation
      of expression of the oncogenes (C-MYC and BCL2), the p53 pathway described above,
      and the apoptosis marker TGF-beta 1 in the human Raji lymphoma following MP
      treatment. Raji xenografts were grown in nude mice and growth curves
      characterized by sequential measurement. Mice were treated daily for 8 days with
      MP. Tumors were harvested untreated, or at 1 or 8 days after cessation of MP
      treatment, and the RNA was extracted. RT-PCR was used to determine the level of
      mRNA expression of the genes. Tumor growth was greatly reduced in the MP-treated
      mice. Gene expression levels for C-MYC and BCL2 were reduced at 1 day following
      MP and approached control levels 8 days after MP treatment. Expression levels of
      p53, CDKN1, and GADD45 were moderately and coordinately decreased at 1 day after
      cessation of MP treatment and remained repressed a week later. TGF-beta 1
      exhibited no change in expression levels. These results suggest that decreased
      expression of C-MYC and BCL2 may play a role in the molecular events that
      initiate and are responsible for the growth inhibition of Raji lymphoma
      xenografts by MP.

PMID- 9169091
TI  - Serum immunoreactive leptin concentrations in patients with anorexia nervosa
      before and after partial weight recovery.
AB  - Leptin, the product of the ob gene, is a recently discovered hormone secreted by
      adipocytes. Serum leptin concentrations increase in correlation with the
      percentage of body fat, but besides that little is known about the physiological
      actions of leptin in humans. In order to understand the role of leptin in severe
      malnutrition, in the present work 10 patients recently diagnosed with anorexia
      nervosa were studied both before and 2 months later, after partial weight
      recovery, and were compared with 18 normal-weight women as controls. Leptin was
      measured by a newly developed radioimmunoassay and both IGF-I and IGFBP-3 were
      measured by commercial radioimmunoassays. The mean (+/-SE) serum leptin
      concentrations (in microgram/liter) were 18.1 +/- 2.0 in control women with BMI
      of 21.1 +/- 0.3, significantly higher (P < 0.01) than that in the anorexia
      nervosa patients at diagnosis (2.2 +/- 0.1, BMI 15.3 +/- 0.6). These differences
      were also observed in IGF-I values (microgram/liter) that were 228.0 +/- 14.6 in
      controls and 157.4 +/- 28.7 in anorexia nervosa patients (P < 0.02). No
      differences were observed in IGF-BP3. After treatment, patients with anorexia
      nervosa experienced an increase in BMI (17.1 +/- 0.5, P < 0.0001 vs before)
      although they were still underweight. The partial recovery in weight led to a
      complete normalization of IGF-I levels (214.0 +/- 21.0 micrograms/liter) and to
      an enhancement in leptin levels (3.3 +/- 0.5 micrograms/liter; P < 0.03 vs before
      treatment), though still lower than those in normal-weight women (P < 0.05).
      Individually analyzed, a large dispersion was observed in control subjects, with
      leptin levels ranging from 5.5 to 38.7 micrograms/liter, while in all anorexia
      nervosa patients leptin levels were under 3 micrograms/liter. A treatment-induced
      increase in body weight led to an increase in leptin levels in 7 out of the 10
      anorexia nervosa patients studied and the 3 patients with no increase in leptin
      were all initially under the 14.5 BMI. In conclusion, leptin levels are severely
      reduced in anorexia nervosa patients with severe malnutrition, and a significant
      rise occurred after partial weight recovery. There seems to be a level of BMI
      below which leptin levels do not drop further but also do not increase despite
      weight gain. While IGF-I reflects the energy intake of the previous few weeks,
      the serum leptin concentration reflects the true status of the adipose stores, a
      fact that has useful clinical implications.

PMID- 9169092
TI  - Expression of PAX3 in Ewing's sarcoma family of tumors.
AB  - The Ewing's sarcoma family of tumors (ESFT) is the second most common pediatric
      malignancy originating in the bone and is characterized by the t(11; 22)
      translocation. PAX3, a member of the paired box family of genes, is expressed
      during embryonal development of neural crest cells and is involved in the t(2;
      13) translocation found in alveolar rhabdomyosarcoma. Since ESFTs are believed to
      be derived from neural crest tissue, we screened a series of Ewing's sarcoma and
      peripheral neuroectodermal tumor cell lines and tumor specimens for expression of
      PAX3. We found expression of PAX3 in most, but not all, of the specimens
      analyzed, including cell lines and patient material.

PMID- 9169093
TI  - Oral ingestion of mannose elevates blood mannose levels: a first step toward a
      potential therapy for carbohydrate-deficient glycoprotein syndrome type I.
AB  - Carbohydrate-deficient glycoprotein syndrome type I (CDGS) is an inherited
      metabolic disorder with multisystemic abnormalities resulting from a failure to
      add entire N-linked oligosaccharide chains to many glycoproteins. Fibroblasts
      from these patients also abnormally glycosylate proteins, but this lesion is
      corrected by providing 250 microM mannose to the culture medium. This correction
      of protein glycosylation suggests that providing dietary mannose to elevate blood
      mannose concentrations might also remedy some of the underglycosylation observed
      in these patients. We find that ingested mannose is efficiently absorbed and
      increases blood mannose levels in both normal subjects and CDGS patients. Blood
      mannose levels increased in a dose-dependent fashion with increasing oral doses
      of mannose (0.07-0.21 g mannose/kg body weight). Peak blood mannose
      concentrations occurred at 1-2 h following ingestion and the clearance half-time
      was approximately 4 h. Doses of 0.1 g mannose/ kg body weight given at 3-h
      intervals maintained blood mannose concentrations at levels 3- to 5-fold higher
      than the basal level in both normal controls (approximately 55 microM) and CDGS
      patients. No side effects were observed for this dosage regimen. These results
      establish the feasibility of using mannose as a potential therapeutic dietary
      supplement (nutraceutical) to treat CDGS patients.

PMID- 9169094
TI  - Insulin resistance and the transcription of the glucose-6-phosphatase gene in
      newborn dogs.
AB  - In the present report changes in the mRNA level of glucose-6-phosphatase (G6Pase;
      EC 3.1.39) in newborn and adult dogs in vivo were studied to further test the
      hypotheses that neonatal hyperglycemia may be due to unsuppressed gluconeogenesis
      by insulin and that the antidiabetic role of insulin-like growth factor-1 (IGF-1)
      may be intact in newborn dogs who have consistently demonstrated insulin
      resistance. Our results were the following: (i) Both renal and hepatic G6Pase
      mRNA were expressed at birth and increased with time during a 24-h period of
      fasting after birth. (ii) The renal G6Pase mRNA levels in newborn dogs did not
      respond to either insulin or epinephrine. (iii) Hyperinsulinemia lowered the
      liver G6Pase mRNA by only 16.3% in newborn dogs, but reduced the liver G6Pase
      mRNA to an undetectable level in adult dogs. (iv) Hyperglycemia decreased the
      hepatic G6Pase mRNA by 14.3% in newborn dogs under hyperinsulinemia. (v) Infused
      epinephrine did not elevate the hepatic G6Pase mRNA level in newborn dogs in the
      presence of hyperglycemia and hyperinsulinemia. (vi) In newborn dogs, hyper-IGF-1
      rapidly reduced the hepatic G6Pase mRNA level by 50%, and hypoglycemia was unable
      to elevate the hepatic G6Pase mRNA level under the hyper-IGF-1. We concluded that
      the reduced rate of suppression of transcription of the liver G6Pase gene by
      insulin in newborn dogs may reflect the unsuppressed neonatal hepatic
      gluconeogenesis due to insulin resistance and that the physiological roles of IGF
      1 seemed to be intact in newborn dogs and may be not responsible for neonatal
      hyperglycemia.

PMID- 9169095
TI  - Expression of myogenic regulatory factors in normal and dystrophic mice: effects
      of IGF-1 treatment.
AB  - Myogenic regulatory factors (MRFs) promote differentiation of muscle cells from
      fibroblasts and are induced by insulin-like growth factor I (IGF-1). Prior
      studies have shown synthesis of new muscle protein and improved muscle morphology
      when mature dy mice with muscular dystrophy are treated with IGF-1. We
      investigated whether these salutary effects of IGF-1 might be attributable to
      stimulation of MRFs. Male dy (129ReJ) mice and controls (129J) were assigned to
      IGF-1 treatment (10 micrograms twice daily) or non-treatment at about 5 weeks of
      life and sacrificed 6 weeks later. RNA was extracted from skeletal muscles,
      reverse transcribed, and amplified by polymerase chain reaction (PCR) using
      primers specific for each MRF. Competitive PCR was performed to quantify MyoD
      expression in response to IGF-1 treatment. Transcripts for myf-5, MRF4, and
      myogenin were detected in both control and dy mouse muscles; no apparent
      differences were observed between treatment groups. Quantitative analysis of
      transcripts for MyoD indicated no significant basal differences between control
      and dy mice. There was, however, significantly higher MyoD expression in the dy
      group, and a trend toward significance in the control group, following IGF-1
      treatment. These data suggest that IGF-1 exerts its in vivo effects in
      postembryonal muscle by stimulating MRFs.

PMID- 9169096
TI  - Effects of four organohalogen environmental contaminants on cytochrome P450 forms
      that catalyze 4- and 2-hydroxylation of estradiol in the rat liver.
AB  - The four environmental pollutants studied (3,3',4,4',5-pentachlorobiphenyl,
      2,2',4,4'-tetrabromodiphenyl ether, Tris-(p-chlorophenyl)methanol, and 3,4,5
      trichloroguaiacol) were all found to induce a significant increase in 4
      hydroxylation of estradiol activity in male rat liver microsomes. However, only
      3,3',4,4',5-pentachlorobiphenyl was found to significantly increase 4- and 2
      hydroxylation of estradiol in female rat liver microsomes. 4-Hydroxylation has
      been suggested to be responsible for the development of estrogen-dependent tumors
      and, therefore, it cannot be excluded that these pollutants can be a risk for the
      development of estrogen-dependent tumors in humans and wildlife.

PMID- 9169097
TI  - Oxidation of bilirubin by brain mitochondrial membranes--dependence on cell type
      and postnatal age.
AB  - Bilirubin is oxidized by brain mitochondrial membranes at a rate which may
      contribute significantly to clearance of bilirubin from the brain. Neurons appear
      to be more sensitive to bilirubin toxicity than glial cells. Clinical experience
      has suggested that sensitivity to bilirubin neurotoxicity may be greater in the
      neonate than later in life. We hypothesized that the ability to oxidize bilirubin
      would be lower in mitochondrial membranes from a pure neuronal compared to a
      mixed glial/neuronal source, and lower in immature than more mature brains.
      Mitochondria of synaptosomal and nonsynaptosomal origin were obtained from young
      rat brains by differential centrifugation in sucrose gradients. Synaptosomes were
      lysed by hypoosmotic treatment, and mitochondria were ruptured by sonication. The
      change in optical density of a bilirubin solution at 440 nm was measured over
      time following addition of the membrane suspension. The rate of bilirubin
      oxidation was significantly higher in nonsynaptic than in synaptic mitochondrial
      membranes [99.1 +/- 42.3 (mean +/- SD) vs 69.9 +/- 30.9 pmol/ min/mg protein, t =
      4.835, P = 0.0003]. "Crude" mitochondrial membranes were obtained by differential
      centrifugation in sucrose from the forebrains of rats of 7, 14, and 21 days
      postnatal age as well as adults, and from rabbits of 1 and 7 days postnatal age
      as well as adults. In both species the rates of bilirubin oxidation increased
      significantly with postnatal age (rats: F = 55.3, P < 0.0001; rabbits: F = 101, P
      < 0.0001). Mitochondrial membranes from a pure neuronal source oxidize bilirubin
      at a significantly lower rate than membranes from a mixed glial/neuronal source.
      This suggests that neurons may be less able to detoxify bilirubin locally and
      thus might contribute to the apparent higher sensitivity to bilirubin toxicity in
      these cells vs glia. Similarly, the lower bilirubin-oxidizing ability of
      mitochondrial membranes from immature brains seems compatible with the clinical
      impression of increased vulnerability to bilirubin neurotoxicity in the newborn.

PMID- 9169098
TI  - Detection of Epstein-Barr viral DNA in serum using rapid-cycle PCR.
AB  - Our study describes the comparison of a rapid nested PCR assay to standard
      serology techniques for the detection of Epstein-Barr virus (EBV) in serum. The
      sera of 81 patients with suspected EBV infection were analyzed; 54 were positive
      for one or more of the standard serology markers, i.e., IgM viral capsid antigen
      (VCA), IgG-VCA, Epstein-Barr nuclear antigen 1 (EBNA-1), and early antigen (EA),
      and 27 were negative for all serology markers. The sera from 15 normal healthy
      blood donors were also included. No EBV DNA was detected in any of the 15 blood
      donor samples or in any of the 27 samples with negative serology results. Eleven
      samples (20%) of the 54 with positive EBV serology results were positive for EBV
      DNA. Of these samples, 9 were EBV IgM-VCA positive and anti-EBNA negative,
      suggesting acute infection. One of the 11 samples had high titers of IgM-VCA, IgG
      VCA, anti-EBNA, and anti-EA. The last of the 11 samples was from a patient with
      acute infectious mononucleosis without sufficient sample volume for EBV serology
      testing. Seventeen of the total 96 samples from the study were IgM-VCA positive
      and anti-EBNA negative and 9 of these 17 samples (53%) tested positive for EBV
      DNA. These data suggest that the detection of EBV DNA by PCR in serum may be a
      useful indicator of active infection rather than latent virus.

PMID- 9169099
TI  - Identification of a ferritin light chain pseudogene near the glycerol kinase
      locus in Xp21 by cDNA amplification for identification of genomic expressed
      sequences.
AB  - We used cDNA amplification for identification of genomic expressed sequences
      (CAIGES) to identify genes in the glycerol kinase region of the human X
      chromosome. During these investigations we identified the sequence for a ferritin
      light chain (FTL) pseudogene in this portion of Xp21. A human liver cDNA library
      was amplified by vector primers, labeled, and hybridized to Southern blots of
      EcoRI-digested human genomic DNA from cosmids isolated from yeast artificial
      chromosomes in the glycerol kinase region of Xp21. A 3.1-kb restriction fragment
      hybridized with the cDNA library, was subcloned and sequenced, and a 440-bp
      intronless sequence was found with strong similarity to the FTL coding sequence.
      Therefore, the FTL pseudogene that had been mapped previously to Xp22.3-21.2 was
      localized specifically to the glycerol kinase region. The CAIGES method permits
      rapid screening of genomic material and will identify genomic sequences with
      similarities to genes expressed in the cDNA library used to probe the cloned
      genomic DNA, including pseudogenes.

PMID- 9169100
TI  - Developmental aspects of transcription of fructose-1,6-bisphosphatase in newborn
      dogs.
AB  - Our previous investigations demonstrated that unsuppressed gluconeogenesis under
      hyperinsulinemia in newborn dogs may be a mechanism of neonatal hyperglycemia. In
      the present study, the transcription of the gene for fructose-1,6-bisphosphatase
      (fru-1,6-P2ase; E 3.1.3.11) of newborn dogs was studied under various metabolic
      perturbations (age, suckling, fasting, and hyperinsulinemia). Total RNAs isolated
      from livers and kidneys were hybridized with a rat fru-1,6-P2ase cDNA probe. We
      observed that (i) fru-1,6-P2ase mRNA was expressed in both kidney and liver at
      birth and was about 40 and 80% of those in kidney and liver of adult dog,
      respectively; (ii) suckling decreased the kidney fru-1,6-P2ase mRNA level to 77.8
      +/- 1.7% (24 h) from 100.0 +/- 8.0% (4 h), but increased liver mRNA to 158.6 +/-
      11.4% (24 h) from 100.0 +/- 2.3% (4 h); (iii) during a 24-h period of fasting,
      the kidney fru-1,6-P2ase mRNA level did not change in the first 10 h and then
      increased 18.5% at 24 h, whereas the liver fru-1,6-P2ase mRNA increased ca. 20%
      during the first 10 h and then up to 161.1 +/- 18.0% at 24 h compared to that at
      100.0 +/- 11.4% (0 h); (iv) euglycemic hyperinsulinemia did not change the renal
      fru-1,6-P2ase mRNA level, but lowered the hepatic fru-1,6-P2ase mRNA level to
      56.0 +/- 8.7 from 100.0 +/- 11.8% (fasted controls) in newborn dogs, which was
      identical to that in adult dogs. These data suggest that the fru-1,6-P2ase in
      liver may play a more important role in glucose homeostasis of newborn dogs than
      that in kidney during the first day of their lives and that the incomplete
      suppression of transcription of the hepatic fru-1,6-P2ase gene by insulin in
      newborn dogs may not contribute to neonatal hyperglycemia due to insulin
      resistance.

PMID- 9169101
TI  - Quantitative-competitive polymerase chain reaction for rapid susceptibility
      testing of Mycobacterium tuberculosis to isoniazid.
AB  - The objective of this study was to determine whether quantitative-competitive
      polymerase chain reaction (QC-PCR) can be used for rapid susceptibility testing
      of Mycobacterium tuberculosis (MTB). QC-PCR was used to determine relative
      amounts of mycobacterial DNA inoculated at different isoniazid (INH)
      concentrations. A total of six different INH-sensitive (INH-S) and five INH
      resistant (INH-R) strains were inoculated in the presence of 0.0, 0.2, 1.0, and
      10.0 micrograms/ml of INH. DNA was quantified using QC-PCR at Week 0 and weekly
      thereafter for 3 weeks. For the QC-PCR, 10-fold dilutions of control (240 bp) DNA
      having the same primer set as the target DNA (123 bp) were used. The amount of
      target DNA was estimated by using known amounts of the internal standard. For INH
      S isolates there was > or = 1 log difference in DNA concentration in the presence
      of each INH concentration compared to that of the control within 1 to 3 weeks. In
      contrast, for INH-R isolates there were no apparent differences in DNA
      concentration between the control suspensions and those containing 0.2 and 1.0
      microgram/ml INH during the 3-week incubation period. The highest INH
      concentration (10 micrograms/ml), however, did abolish the DNA increase seen in
      the other MTB suspensions. This preliminary study suggests that by using
      concentrations of 0.2 or 1.0 microgram/ml of INH, QC-PCR may differentiate INH-R
      and INH-S MTB isolates within 1 week. This method may be of particular value when
      applied directly to clinical specimens with varying numbers of bacilli.

PMID- 9169102
TI  - Serotonin decreases cytoskeletal and cytosolic glycolytic enzymes and the levels
      of ATP and glucose 1,6-bisphosphate in skin, which is prevented by the calmodulin
      antagonists thioridazine and clotrimazole.
AB  - Serotonin (5-hydroxytryptamine) is believed to play a pathogenic role in skin
      damage and various skin abnormalities; however, its mechanism of action remains
      unknown. We show here that intradermal injection of serotonin in rats induced a
      marked reduction in the activities of the glycolytic enzymes, phosphofructokinase
      (EC 2.7.1.11) and aldolase (EC 4.1.2.13), in both the cytoskeletal and cytosolic
      fractions from skin. Serotonin also decreased the levels of glucose 1,6
      bisphosphate in skin, the powerful regulator of glucose metabolism. These
      serotonin-induced changes were accompanied by a marked decrease in ATP content in
      skin. All these pathological changes induced by serotonin were prevented by
      treatment with two structurally different calmodulin antagonists: thioridazine,
      an antipsychotic phenothiazine, or clotrimazole, from the group of the antifungal
      azole derivatives that were recently recognized as calmodulin antagonists. The
      present results suggest that calmodulin antagonists may be effective drugs in the
      treatment of skin damage under various pathological conditions and diseases in
      which serotonin levels are increased.

PMID- 9169103
TI  - Storage phosphor radiography.
AB  - Storage phosphor radiography is a digital technique that uses photo-stimulable,
      phosphor screens to substitute for conventional screen-film combinations. While
      the technique is more than 15 years old, it is only recently that technological
      and economic aspects of these systems have become favourable enough to envisage a
      more widespread clinical application.

PMID- 9169104
TI  - Digital radiography for clinical applications.
AB  - In the field of radiological research methods, digital imaging is becoming
      increasingly prevalent. Apart from computerised tomography, magnetic resonance
      tomography and angiography, also in projection radiography, traditional
      film/screen imaging is more and more being replaced by digital imaging using
      digital image-intensifier and storage phosphor technology. Digital imaging offers
      various new possibilities in image processing, storage and transmission. This may
      yield additional diagnostic information, dose reduction and fast availability of
      images. However, an inappropriate parameter selection for imaging and post
      processing as well as a lack of integration in the entire organisation may lead
      to a rejection of this innovative technology.

PMID- 9169105
TI  - Digital image processing.
AB  - The image quality of a radiograph is determined by the local contrast, spatial
      resolution, latitude and the image noise. The goal of digital processing is to
      improve the visualisation of pathology by optimising these physical parameters.
      Processing parameters need to be chosen correctly in order to overcome the
      inverse relationship between contrast and latitude while producing images that
      retain a conventional appearance. Unsharp mask filtering (UMF) is a simple
      technique for improving image quality. This technique, however, suffers from
      serious drawbacks, such as the suppression of pathologic lesions or artifacts
      that may simulate pathology. Manufacturers have developed different approaches in
      order to overcome problems and artifacts derived from this technique.

PMID- 9169106
TI  - Stimulable phosphor plates in chest radiology.
AB  - The stimulable phosphor plate technique has revolutionised radiology with
      portable equipment. The image quality permits diagnosis under difficult control
      conditions (ICUs). In order to achieve a signal-to-noise ratio, and therefore a
      contrast resolution similar to the commonly used film/screen systems, a higher
      radiation dose is needed. However, overall, with this technique a radiation dose
      reduction may be achieved as a result of the elimination of the need for retakes.
      The available stimulable phosphor plate systems, with adequate image processing
      are reliable, and at least as good as conventional film/screen systems for
      diagnosis in chest radiography. There are, however, other aspects that make the
      stimulable phosphor plate technique particularly appealing. Firstly, its
      reproducibility, which particularly in chest radiography allows images to be
      obtained with the same grey scale and darkness. Secondly, as this technique
      permits digital archiving and visualisation of images on screen, images can be
      rapidly distributed over a network making them available when and where they are
      needed.

PMID- 9169107
TI  - Maintaining efficiency in a satellite radiology department.
AB  - In this paper the organisation of a radiology satellite department is described.
      In the satellite department only bucky examinations are performed, thus avoiding
      the need for the duplication of sophisticated material and specialized staff. The
      satellite department maintains as efficient a service as the main radiology
      department. For this purpose a digital radiology system was chosen for the
      satellite department. This system permits digital data to be sent to the main
      location. This results in a maximisation of the advantages of a two-location
      system as well as avoiding the need for patients' files to be moved between
      different locations.

PMID- 9169108
TI  - Computer integrated radiology system: analogue goes digital.
AB  - At the end of 1995, a pilot project of a year and a half was successfully
      completed. The project had two main objectives. On the one hand, the aim was to
      have a performant analogue X-ray system replaced by a digital system. On the
      other, modalities of various manufacturers had to be integrated and evaluation
      had to be done on-screen. Within the scope of QA, this paper deals with a
      comparative study on the hard- and soft copy evaluation of 90 selected intensive
      thorax radiographs. A further element in our study was the adjusted work-flow of
      radiological technical assistants as well as a comparison of dose measurements in
      conventional and digital systems.

PMID- 9169109
TI  - Digital radiography. Results of a survey (part A) and a consensus conference
      (part B).
AB  - Digital imaging (digital image intensifier radiography, storage phosphor/selenium
      radiography) is increasingly becoming commonplace in radiology departments for
      diagnostic purposes. Despite 10 years of experience, the advantages and
      disadvantages of those methods are still heavily discussed among users,
      financiers and prescribers. This paper is to offer additional arguments for a
      thorough and objective discussion. No further comments or interpretations have
      been added to this paper. This paper consists of two main parts, A and B. The
      first part deals with the results of a user survey, the other part presents the
      results, i.e. statements, of a consensus conference.

PMID- 9169110
TI  - The influence of corticosterone and glucagon on metabolic recovery from
      exhaustive exercise in the desert iguana Dipsosaurus dorsalis.
AB  - The skeletal muscles of ectothermic vertebrates possess an elevated glyconeogenic
      capacity that is responsible for a major portion of lactate removal and glycogen
      resynthesis following exercise. In lizards, changes in plasma hormone levels and
      the influence of differing hormone levels on muscle metabolism postexercise are
      poorly understood. We measured the effects of 5 min of exhaustive exercise on
      plasma levels of glucagon and corticosterone in the desert iguana Dipsosaurus
      dorsalis. We also determined the extent to which these hormones influence, or are
      influenced by, postexercise plasma lactate concentrations postexercise. Exercise
      resulted in the accumulation of 20 mM blood lactate, while plasma glucose levels
      remained stable throughout 90 min of recovery. Plasma glucagon was elevated
      sevenfold during 5 min of exercise and returned to resting levels within 45 min
      of recovery. Glucagon stimulated lactate incorporation into glycogen in isolated
      red muscle fiber bundles. Plasma corticosterone was also elevated to three times
      normal resting values, but only after 45 min of recovery. Blocking corticosterone
      elevation with metyrapone did not alter the kinetics of plasma lactate removal.
      In lizards, the dramatic rise in plasma glucagon occurs at the same time as
      previously reported elevated skeletal muscle glyconeogenesis and elevated
      glucagon stimulates lactate removal in vitro, strongly suggesting a role for
      glucagon in postexercise skeletal muscle metabolism.

PMID- 9169111
TI  - Immunolocalization of aromatase- and androgen receptor-positive neurons in the
      goldfish brain.
AB  - Full expression of testosterone (T) actions in the brain requires both direct
      binding to androgen receptors (AR) and in situ aromatization to estradiol (E2).
      To determine the cellular basis of constitutively high aromatase and AR binding
      activities in teleost fish brain, and the neuroanatomic location and spatial
      relations of cells of each type, an immunocytochemical mapping study of goldfish
      (Carassius auratus) brain was carried out using antibodies to human placental
      aromatase and human/rat AR peptide and the avidin-biotin-peroxidase technique.
      Both antibodies specifically labeled cells that were neuronal in appearance and
      were most numerous in reproductive control centers: medial and ventral
      telencephalon (TEL) and preoptic and hypothalamic periventricular nuclei.
      Additional populations of aromatase- and AR-labeled cells were present in the
      olfactory bulbs, central telencephalon, and stratum periventriculare of the optic
      tectum. Anti-aromatase, but not anti-AR, labeled fiber tracts and fibrous layers
      in visual and auditory pathways, and perikarya and processes of premotor neurons
      known to integrate sensory input (reticulospinal neurons, Mauthner cells). Anti
      AR selectively labeled lateral TEL regions, the nucleus ventromedialis thalami,
      and discrete cell clusters in the medial tegmental nucleus. Aromatase
      immunoreactivity (-ir) was primarily cytoplasmic, whereas AR-ir was primarily
      nuclear, but relative intensity of nuclear vs cytoplasmic labeling with each
      antibody differed by brain region. Aromatase- and AR-ir cells were not obviously
      more numerous in goldfish brain than previously seen in birds and mammals,
      suggesting that enhanced expression occurs on a per cell basis. We conclude that
      T exerts its actions coordinately via direct and indirect pathways in most brain
      regions but independently via AR- or aromatase-mediated mechanisms in selected
      areas. These studies point to a wide role for androgen in modulating primary
      sensory signals as well as in classical reproductive processes.

PMID- 9169112
TI  - The effect of the aromatase inhibitor fadrozole and two polynuclear aromatic
      hydrocarbons on sex steroid secretion by ovarian follicles of coho salmon.
AB  - A variety of endogenous and exogenous factors can influence sex steroid
      production by salmon ovarian follicles and ultimately impact reproductive
      development. We examined the effect of an aromatase inhibitor, fadrozole, and
      common environmental contaminants (PAHs) on sex steroid secretion by ovarian
      follicles. Ovarian follicles of coho salmon were incubated in vitro with various
      concentrations of testosterone (0.10-0.40 microM) and fadrozole (10 and 100
      microM), or with varying doses (between 0.05 and 5.0 microM) of the PAHs beta
      naphthoflavone (BNF) and 20-methylcholanthrene (20-MC). 17 beta-Estradiol
      secretion was significantly reduced when follicles were incubated in the presence
      of fadrozole, BNF, or 20-MC. In contrast, 17 beta-estradiol production by ovarian
      follicles increased in a dose-dependent manner when incubated with increasing
      doses of the aromatizable androgen testosterone. Although increasing doses of
      PAHs significantly reduced follicular 17 beta-estradiol production no effect on
      testosterone secretion was observed. Hence, both fadrozole and PAHs can
      significantly reduce 17 beta-estradiol secretion by salmon ovarian follicles and
      may affect female sexual development.

PMID- 9169113
TI  - Effects of estradiol on the serotonin secretion and turnover in the hypothalamus
      of male tilapia, Oreochromis mossambicus, in vitro.
AB  - The effects of estradiol on the secretion and turnover of serotonin in the
      hypothalamic fragments of male tilapia, Oreochromis mossambicus, were studied
      using a static incubation system. The quantitative analysis of serotonin and its
      related metabolite, 5-hydroxyindoleacetic acid, were performed by high
      performance liquid chromatography with electrochemical detection. The
      hypothalamic fragments were incubated with 17 beta-estradiol at a concentration
      of 2 x 10(-8), 8 x 10(-8), 2 x 10(-7), 4 x 10(-7), or 4 x 10(-6) g/ml. The low
      dose of estradiol, 2 x 10(-8) g/ml, had no effect on the concentration of
      serotonin and 5-hydroxyindoleacetic acid or serotonin turnover in the
      hypothalamic incubation media. The moderate doses of estradiol 8 x 10(-8) and 2 x
      10(-7) g/ml, increased the concentrations of serotonin and 5-hydroxyindoleacetic
      acid in the hypothalamic incubation media, but had no effect on the serotonin
      turnover. The high doses of estradiol, 4 x 10(-7) and 4 x 10(-6) g/ml, did not
      alter the serotonin concentration in the hypothalamic incubation media, but
      increased the 5-hydroxyindoleacetic acid concentration and serotonin turnover.
      These results demonstrate that the moderate dose of estradiol increases the
      serotonin activity by increasing the serotonin concentration, whereas the high
      dose of estradiol increases the serotonin activity by increasing the ratio of 5
      hydroxyindoleacetic acid and serotonin. However, the serotonin concentration is
      homeostatically maintained in the extracellular fluid of hypothalamus under the
      high dose of E2 treatment.

PMID- 9169114
TI  - Development of a time-resolved fluoroimmunoassay (TR-FIA) for testosterone:
      measurement of serum testosterone concentrations after testosterone treatment in
      the rainbow trout (Oncorhynchus mykiss).
AB  - A sensitive time-resolved fluoroimmunoassay (TR-FIA) for testosterone was
      developed, and the assay system was used for measuring serum testosterone
      concentrations in rainbow trout. Testosterone-3-(O-carboxymethyl)oxime-bovine
      serum albumin (T-3-CMO-BSA) was immobilized by physical adsorption to the wells
      of microtiter plates. A competitive assay using two antibodies was performed
      among T-3-CMO-BSA in the solid-phase, unknown amounts of testosterone,
      testosterone antibodies, and europium labeled secondary antibodies, followed by
      measurements using a time-resolved fluorometer (DELFIA system). The TR-FIA had a
      sensitivity of 0.075 pg/50 microliters sample (1.5 pg/ml), and the range of the
      assay system was between 1.5 pg/ml and 25 ng/ml. The intra- and interassay
      coefficients of variation for the testosterone TR-FIA were satisfactorily low,
      and were between 1.62 and 6.38% and 2.96 and 8.29%, respectively. The assay
      system was applied to measure the serum testosterone concentrations after an
      injection of testosterone dissolved in saline, propyleneglycol, or coconut oil.
      Among the three solvents, the coconut oil group showed continuously high serum
      testosterone level. In contrast, the saline and propyleneglycol groups had
      maximum concentrations 24 hr after the injection, but their levels were
      significantly lower than that of the coconut oil group. The testosterone TR-FIA
      method is sensitive, repeatable, and is as accurate as conventional RIAs. It is
      very good for measuring serum testosterone concentrations.

PMID- 9169115
TI  - Ovarian receptors for insulin and insulin-like growth factor I (IGF-I) and
      effects of IGF-I on steroid production by isolated follicular layers of the
      preovulatory coho salmon ovarian follicle.
AB  - In this study, receptors for insulin and insulin-like growth factor I (IGF-I) in
      isolated theca-interstitial layers and granulosa cells of the coho salmon
      preovulatory ovary were characterized, and the effects of IGF-I on ovarian
      steroidogenesis were examined. Specific receptors for insulin and IGF-I were
      found in granulosa and theca-interstitial layers. In both follicular layers, IGF
      I receptors were greater in number and higher in affinity than insulin receptors.
      The effects of IGF-I on in vitro production of testosterone (T) and 17 alpha
      hydroxyprogesterone (17OH-P) by theca-interstitial layers and of 17 beta
      estradiol (E2) and 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) by
      granulosa cell layers were evaluated during the preovulatory period. Both human
      and salmon recombinant IGF-I inhibited the basal and GTH II-stimulated T and 17OH
      P production by theca-interstitial layers throughout the preovulatory period. In
      contrast, IGF-I stimulated the production of both E2 and 17,20 beta-P by
      granulosa cell layers prior to germinal vesicle breakdown (GVBD) but only
      stimulated the production of 17,20 beta-P by granulosa cell layers after GVBD.
      The inhibitory effects of IGF-I on steroid production by the theca-interstitial
      layer and the opposite stimulatory effects on steroid production by the granulosa
      cell layer, coupled by the presence of specific IGF-I receptors in both
      follicular layers, suggest that IGF-I may play a role in the regulation of
      steroidogenesis in the preovulatory coho salmon ovary.

PMID- 9169116
TI  - Thyroid hormone deiodination in various tissues of larval and upstream-migrant
      sea lampreys, Petromyzon marinus.
AB  - Properties and activities of four potential thyroid hormone (TH) monodeiodinating
      pathways (T4ORD, L-thyroxine (T4) outer-ring (5') deiodination to 3,5,3'-triiodo
      L-thyronine (T3); T4IRD, T4 inner-ring (5) deiodination to 3,3',5'-triiodo-L
      thyronine (reverse T3); T3ORD, T3 outer-ring deiodination to 3,5-diiodo-L
      thyronine; T3IRD, T3 inner-ring deiodination to 3,3'-diiodo-L-thyronine) were
      studied in microsomes of liver, kidney, muscle, and intestine of unmetamorphosed
      larvae and nontrophic upstream-migrant (spawning-phase) sea lampreys, Petromyzon
      marinus. T4ORD properties (pH optimum, dithiothreitrol cofactor requirement,
      apparent K(m), substrate preference and potency of potential inhibitors) were
      similar in most respects to those described previously for teleosts. T4ORD
      activity was detected in all larval tissues examined and was highest in
      intestine. In upstream migrants, T4ORD was also greatest in intestine, but low in
      muscle and kidney and undetectable in liver. T3ORD activity was not found in any
      tissue of either developmental stage. T4IRD and T3IRD activities were negligible
      in larval tissues, but present in kidney and particularly intestine of upstream
      migrants. We conclude that depending on developmental/physiological state, sea
      lampreys possess low-K(m) outer-ring and inner-ring monodeiodinases, which in
      most respects correspond functionally with those of teleosts. However, in
      contrast to teleosts, deiodination is particularly active in larval intestine,
      perhaps reflecting the release from the endostyle of TH into the lumen of the
      alimentary canal.

PMID- 9169117
TI  - The effects of exogenous thyroxine (T4) or triiodothyronine (T3), in the presence
      and absence of potassium perchlorate, on the incidence of metamorphosis and on
      serum T4 and T3 concentrations in larval sea lampreys (Petromyzon marinus L.).
AB  - Larval sea lampreys (Petromyzon marinus) measuring 100-119 mm in length were
      exposed to thyroxine (T4; 10 mg liter-1) or 3,5,3'-triiodothyronine (T3; 1 mg
      liter-1) in the presence and absence of the goitrogen potassium perchlorate
      (KClO4; 0.01%), for 4-24 weeks. Every 4 weeks, treated and untreated (control)
      groups of sea lampreys were examined for external signs of metamorphosis and
      serum was assayed for T4 and T3 concentrations. Precocious metamorphosis was
      observed following 8, 12, and 24 weeks of KClO4 treatment; however, metamorphosis
      was not observed in any control, or T4-, T3-, T4+KClO4-, and T3+KClO4-treated
      larvae. In addition, serum T4 and T3 concentrations were 62 and 72% lower in
      KClO4-treated individuals than in control animals, respectively. Treatment with
      exogenous thyroid hormones (TH), in the presence or absence of KClO4, resulted in
      serum T4 concentrations which were significantly greater (1.2- to 58-fold) than
      those of the controls in all sampling periods except one, but serum T3
      concentrations were not significantly elevated in more than 50% of the cases.
      TH+KClO4 treatments produced serum T3 concentrations which were significantly
      greater than those of KClO4-treated animals and never less than those of
      controls. These data indicate that larval sea lampreys have a tremendous capacity
      to take up and store exogenous T4 in their serum, but the uptake and/or serum
      storage of T3 appears to be stringently regulated. Also, the absence of both
      metamorphosis and a decline in serum TH concentrations in TH+KClO4-treated
      animals suggests that a decline in serum TH concentrations may be an essential
      factor contributing to the induction of metamorphosis by KClO4.

PMID- 9169118
TI  - Effects of polychlorinated biphenyl mixtures and three specific congeners on
      growth and circulating growth-related hormones.
AB  - Polychlorinated biphenyls (PCB) are ubiquitous environmental contaminants that
      bioaccumulate in avian species. Exposure to PCBs can result in decreased growth.
      Thyroid hormones and growth hormone (GH) are important for normal growth. The
      present studies employed the chicken embryo to investigate effects of Aroclor
      1242, Aroclor 1254, 2,2',6,6'-tetrachlorobiphenyl (TCB), 3,3',4,4'-TCB, and
      3,3',5,5'-TCB on growth and growth-related hormones. The following indices were
      measured: embryo mortality, body weights, bone length, pituitary GH content, and
      plasma concentrations of triiodothyronine (T3), thyroxine (T4), GH, and insulin
      like growth factor-1 (IGF-1). Fertile eggs were injected with PCBs on Day 0 and
      indices determined on Day 17 of incubation. Unexpectedly, 3,3',5,5'-TCB or low
      dose Aroclor 1242 treatment increased body weight and bone length (P < 0.05),
      whereas Aroclor 1242 (high dose), 3,3,4,4'-TCB, or Aroclor 1254 treatment reduced
      body weights and/or bone length (P < 0.05). Aroclor 1242 or 3,3',4,4'-TCB (low
      dose treatment) elevated plasma T4 concentrations (P < 0.05). Both growth and
      pituitary GH content were increased (P < 0.05) by 3,3',5,5'-TCB (low dose) or
      Aroclor 1242 treatment. Despite marked differences in growth rates, plasma T3,
      GH, and IGF-I concentrations were unaffected by PCB treatment. Growth-related
      hormones may not be responsible for the growth depression observed after PCB
      treatment. Possibly the decrease in growth occurred because of general toxicity.
      The importance of chlorine position in causing thyroid hormone axis alterations
      was not clearly established.

PMID- 9169119
TI  - False positive immunostaining of Locusta neurosecretory cells with a variety of
      preimmune sera.
AB  - A large number of antisera directed against vertebrate neuropeptides have been
      reported to yield positive staining when applied to insect brains. In most cases,
      the preimmune serum of the same animal in which the antiserum was developed is
      not available for testing in control experiments. We have experienced that a
      large percentage of preimmune sera, as well as a culture medium for hybridomas,
      stain cell populations and fibers in the central nervous system of the insect
      Locusta migratoria. Purification of these preimmune sera on a Protein A and
      Protein G support indicates that the reaction is due to preexisting antibodies of
      the IgG class. Western analysis of brain and nervous tissue extracts indicates
      the presence of two immunoreactive 27-kDa bands. These bands could also be
      visualized in other tissue extracts such as muscle, midgut, Malpighian tubules,
      and fat body of Locusta. The brain of other insect species, such as Periplaneta
      americana, Leucophaea maderae, and Neobellieria bullata were devoid of the false
      immunopositive reaction. There is no easy way to eliminate this type of
      immunoreaction. It follows that when affinity chromatographic purification of the
      antibody is not feasible, it is essential to include in the control procedure,
      the preimmune serum of the animal that was used for the production of the
      antiserum. This means that it should become common practice to sell or exchange
      sera together with their corresponding preimmune sera.

PMID- 9169120
TI  - Cockroach allatostatin-like immunoreactivity in the central nervous system of the
      freshwater snails Bulinus globosus (Planorbidae) and Stagnicola elodes
      (Lymnaeidae).
AB  - Allatostatin-like immunoreactivity was demonstrated in the central nervous system
      (CNS) neurons of the freshwater pulmonate snails Bulinus globosus (Planorbidae)
      and Stagnicola elodes (Lymnaeidae). Immunopositive neurons were localized using a
      monoclonal antibody highly specific to allatostatin I (APSGAQRLYGFGL-amide) from
      the cockroach Diploptera punctata. All CNS ganglia in both snail species
      contained immunopositive neurons. The pedal ganglia showed large numbers (80-100)
      of neurons in Bulinus and Stagnicola. Large numbers of immunopositive cells were
      also found in the cerebral (60) and buccal ganglia (20) of Bulinus. Other ganglia
      contained fewer immunopositive cells, but these cells were most concentrated in
      the cerebral (Stagnicola) and left parietal (Bulinus) ganglia and the visceral
      ganglia of both species. The high concentration of immunopositive cells in the
      pedal ganglia and axons demonstrable in the pedal nerves suggests that one
      possible function for a molluscan allatostatin-like peptide would be to modulate
      muscular function. Extract of Stagnicola CNS effected 50% inhibition of juvenile
      hormone synthesis by corpora allata of D. punctata at between 15 and 30 CNS
      equivalents, providing further evidence that the molluscan immunoreactive
      material is a peptide, or peptides, with sequence similarity to the active part
      of the D. punctata allatostatins.

PMID- 9169121
TI  - Modification of gonadotropin releasing hormone (GnRH) mRNA expression in the
      retinal-recipient Thalamus.
AB  - Although the environmental cues that trigger reproductive behaviors are known for
      many species, the mechanisms through which these signals influence the
      neurochemistry of the brain to produce behavior have been elusive. In this study,
      we describe a retinally modulated system of gonadotropin releasing hormone (GnRH)
      producing neurons in the thalamus of the plainfin midshipman fish, Porichthys
      notatus. Previously, we cloned and sequenced the cDNA for prepro-GnRH in
      midshipman. Here, using in situ hybridization, we localized prepro-GnRH mRNA to
      the ventrolateral nucleus of the thalamus, three divisions of the preoptic area,
      the ganglion of the terminal nerve, and the olfactory bulb. Since the thalamus,
      terminal nerve ganglion, and preoptic area have been associated with visual
      functions, we investigated the retinal connections in midshipman. In particular,
      biocytin tract tracing delineated a reciprocal connection between the
      ventrolateral nucleus of the thalamus and the retina. Retinofugal projections are
      exclusively contralateral. Experimental manipulation of this retinalthalamic loop
      through complete optic nerve transection shows that GnRH mRNA expression in the
      contralateral ventrolateral nucleus may be influenced by the retina. We
      hypothesize that a reciprocal retinothalamic GnRH circuit is important in
      modulating the expression of seasonal reproductive behaviors.

PMID- 9169122
TI  - Ontogenic changes in the circulating concentrations of insulin-like growth factor
      (IGF)-I, IGF-II, and IGF-binding proteins in the chicken embryo.
AB  - The ontogeny of circulating concentrations of insulin-like growth factor (IGF-)
      I, IGF-II, and IGF-binding proteins (IGF-BPs) was examined in the chick embryo.
      Distinct ontogenic changes in the circulating concentrations of IGF-I and IGF-II
      were observed. The present study confirms the overall profile for circulating
      concentrations of IGF-I. During middevelopment, plasma concentrations of IGF-I
      increased to a maximum which was attained on Day 14.5 of incubation. Thereafter,
      plasma concentrations of IGF-I declined with decreases (P < 0.05) between Days
      14.5 and 15.5 and between Days 16.5 and 17.5 of incubation. In contrast to the
      monophasic profile for IGF-I, plasma concentrations of IGF-II were maximal on Day
      10.5 of incubation and declined to a nadir on Day 17.5 of incubation. In late
      developmental stages (17.5 or 18.5 days of incubation), three IGF-BPs, having
      molecular weights of 22, 28, and 36 kDa, were detected in the plasma of chick
      embryos. No significant ontogenic changes in the circulating levels of the 28-
      and 36-kDa IGF-BPs were observed. However, it should be noted that prior to Day
      17.5 of incubation, the 22-kDa IGF-BP was nondetectable in the circulation. The
      role of these changes in the functioning of IGF in embryonic development is
      discussed.

PMID- 9169123
TI  - Cloning and characterization of rainbow trout (Oncorhynchus mykiss) somatolactin
      cDNA and its expression in pituitary and nonpituitary tissues.
AB  - A cDNA clone encoding rainbow trout (Oncorhynchus mykiss) somatolactin (rtSL) has
      been isolated from a rainbow trout pituitary cDNA library. This 2329-bp cDNA
      clone includes a very short 7-bp 5'-untranslated region, a coding region of 702
      bp, and a long 3'-untranslated region of 1620 bp. The deduced amino acid sequence
      of rtSL shows a polypeptide of 233 amino acid residues which consists of a 24
      amino-acid putative signal peptide followed by a 209-amino-acid mature
      polypeptide. This mature polypeptide has a molecular weight of 24 kDa. The rtSL
      shares 99% amino acid identity with chum salmon SL (csSL) and approximately 53
      77% amino acid identity with SLs in other fishes, including the 7 conserved
      cysteine residues. Although a glycosylation site has been identified in SL of
      other fish species, none is observed in rtSL polypeptide. The level of rtSL mRNA
      in a single pituitary gland was determined by RNA blot hybridization. Results
      showed that levels of SL mRNA in pituitary glands of 2-year-old fish were 4- to 7
      fold higher than those of 1-year-old fish. The tissue distribution of SL gene
      expression in adult fish was determined by reverse transcription-polymerase chain
      reaction (RT-PCR) and DNA blot hybridization. In addition to the pituitary gland,
      SL mRNA was detected in all tissues examined including brain, gill, heart,
      kidney, liver, skeleton muscle, spleen, ovary, testis, and immature oocytes. The
      extrapituitary expression of the SL gene was also detected in embryos and fry.
      The PCR products which contained the region coding for mature SL from heart and
      kidney were cloned and characterized. Nucleotide sequence analysis showed that
      the SL mRNAs in heart and kidney were identical to that in the pituitary gland.
      These results suggest that, although the pituitary gland is the predominant
      tissue for producing SL, it is not the only tissue that SL gene is expressed in,
      and the extrapituitary expression of rtSL gene starts from very early
      developmental stages.

PMID- 9169124
TI  - Changes in plasma concentrations of luteinizing hormone, progesterone, and
      testosterone in turkey hens during the ovulatory cycle.
AB  - Changes in luteinizing hormone (LH), progesterone, and testosterone
      concentrations were determined in blood samples taken every 10 min for 26 hr
      during an ovulatory cycle in laying turkey hens. During the 26-hr sampling
      period, one peak of both LH and progesterone and numerous peaks of testosterone
      were detected. The concentration of LH in plasma increased from basal level (2.44
      4.0 ng/ml) to maximum level (8.57-24.3 ng/ml) over 1 to 2 hr and then declined
      over 3 to 5 hr to a basal level. The duration of the descending portion of the
      peak was about double that of the ascending portion. The concentration of
      progesterone increased rapidly from a basal level of 1.18-1.65 ng/ml to a peak of
      6.18-11.87 ng/ml and then maintained a plateau before rapidly declining to basal
      level. The concentration of testosterone increased from a basal level of 0.06
      0.09 ng/ml to a peak level of 0.13-0.30 ng/ml. All maximum levels of testosterone
      preceded those of LH, and all maximum levels of LH preceded those of
      progesterone. The durations of the progesterone peaks were longer than those of
      the LH peaks. Progesterone concentrations returned to basal level after LH had
      returned to basal level, although the initial increase in progesterone
      concentration was earlier, later, or at the same time as LH. Peak durations of
      testosterone were variable. The preovulatory surges of LH and progesterone of
      five of nine sets of samples started at the end of the scotophase and ended
      during the beginning portion of the photophase. In three of nine sets both the
      start and the end occurred druing the scotophase and in one of nine sets during
      the photophase. It was concluded from this study that the patterns of secretion
      of LH, progesterone, and testosterone were similar in that the preovulatory surge
      was superimposed on a relatively stable basal level, while the temporal
      relationships of the ovulatory surges of these hormones were variable. The
      preovulatory surges were more tightly associated with ovulation rather than with
      photoperiod. Neither progesterone nor testosterone might be an initiator of the
      LH surge prior to ovulation.

PMID- 9169125
TI  - Identification and characterization of a seven transmembrane hormone receptor
      using differential display.
AB  - Targeted mutagenesis analysis has shown that the Cmyb proto-oncogene, which
      encodes a sequence-specific DNA binding protein, is required for normal murine
      fetal liver erythropoiesis and myelopoiesis. To identify novel genes involved in
      hematopoiesis, differential display analysis was conducted using total liver RNA
      isolated from 14.5-day postcoitus Cmyb wildtype, heterozygous, and homozygous
      mutant littermates. Using 4 oligo(dT) 3' primers and 5 arbitrary decamers as 5'
      primers, 22 differentially expressed genes have been identified. Eight putatively
      novel genes were identified from 12 cDNAs that were sequenced. One gene,
      initially designated DD7A5-7, is primarily expressed in cells of the myeloid
      lineage. The full-length DD7A5-7 cDNA is 3239 nucleotides, encoding a putative
      protein of 931 amino acids. The protein is a member of a family of hormone
      receptors containing 7 transmembrane segments. The receptor also contains 7
      epidermal growth factor-like (Egf-like) motifs at the amino terminal of the
      predicted protein. The gene is alternatively spliced, resulting in the deletion
      of one or more copies of the Egf-like motif. DD7A5-7 maps to mouse Chromosome 17
      and is the putative homologue of EMR1, a recently described Egf-like module
      containing mucin-like hormone receptor with 7 transmembrane segments in humans.
      Our results indicate that the Cmyb mutant fetuses represent a unique resource for
      identifying genes involved in hematopoiesis.

PMID- 9169126
TI  - The genomic organization of the Fanconi anemia group A (FAA) gene.
AB  - Fanconi anemia (FA) is a genetically heterogenous disease involving at least five
      genes on the basis of complementation analysis (FAA to FAE). The FAA gene has
      been recently isolated by two independent approaches, positional and functional
      cloning. In the present study we describe the genomic structure of the FAA gene.
      The gene contains 43 exons spanning approximately 80 kb as determined by the
      alignment of four cosmids and the fine localization of the first and the last
      exons in restriction fragments of these clones. Exons range from 34 to 188 bp.
      All but three of the splice sites were consistent with the ag-gt rule. We also
      describe three alternative splicing events in cDNA clones that result in the loss
      of exon 37, a 23-bp deletion at the 5' end of exon 41, and a GCAG insertion at
      the 3' portion also in exon 41. Sequence analysis of the 5' region upstream of
      the putative transcription start site showed no obvious TATA and CAAT boxes, but
      did show a GC-rich region, typical of housekeeping genes. Knowledge of the
      structure of the FAA gene will provide an invaluable resource for the discovery
      of mutations in the gene that accounts for about 60-66% of FA patients.

PMID- 9169127
TI  - Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and
      Y5 suggests coordinate transcriptional regulation.
AB  - The human y1 and y5 receptor genes are transcribed in opposite directions from a
      common promoter region on chromosome 4q31-q32. One of the alternately spliced 5'
      exons of the y1 receptor gene (1C) is also an integral part of the coding region
      of a novel neuropeptide Y receptor, Y5. Exon 1C of the y1 receptor gene, if
      translated from the opposite strand, encodes sequences corresponding to the large
      third intracellular loop of the Y5 receptor. The close proximity of the two
      neuropeptide Y receptor genes suggests that they have evolved from a gene
      duplication event with the small intron interrupting the coding sequence of the
      y1 gene being converted into a functional sequence within the y5 gene, while the
      reverse complementary sequence was utilized as an alternatively spliced 5' exon
      for the y1 gene. The transcription of both genes from opposite strands of the
      same DNA sequence suggests that transcriptional activation of one will have an
      effect on the regulation of gene expression of the other. As both Y1 and Y5
      receptors are thought to play an important role in the regulation of food intake,
      coordinate expression of their specific genes may be important in the modulation
      of NPY activity.

PMID- 9169128
TI  - Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic
      structure, promoter sequence, and chromosomal localization.
AB  - The mouse dihydrolipoamide dehydrogenase (Dld) gene has been cloned,
      characterized, and mapped. This nuclear gene encodes a mitochondrial protein that
      is shared among several alpha-keto acid dehydrogenase complexes and the glycine
      cleavage system. The Dld gene is contained within an approximately 21-kb region
      and consists of 14 exons ranging in size from 69 to 521 nucleotides. The open
      reading frame codes for a preprotein of 509 amino acids with a predicted mature
      protein of 474 amino acids that is highly conserved among mammalian species (>
      90% identical). Primer extension analyses have shown the gene to have
      transcription initiation sites with tissue-specific differences in relative
      utilization. The 5' flanking region is G-C rich and lacks a TATA box, but does
      contain initiator element and multiple transcription factor-binding consensus
      sequences. Northern blot analysis shows that the Dld mRNA in various tissues is
      approximately 2.4 kb in size. The Dld gene has been localized to the proximal
      region of chromosome 12, approximately 21 cM from the centromere.

PMID- 9169129
TI  - Characterization and chromosomal mapping of the human TFG gene involved in
      thyroid carcinoma.
AB  - Homology searches in the Expressed Sequence Tag Database were performed using
      SPYGQ-rich regions as query sequences to find genes encoding protein regions
      similar to the N-terminal parts of the sarcoma-associated EWS and FUS proteins.
      Clone 22911 (T74973), encoding a SPYGQ-rich region in its 5' end, and several
      other clones that overlapped 22911 were selected. The combined data made it
      possible to assemble a full-length cDNA sequence. This cDNA sequence is 1677 bp,
      containing an initiation codon ATG, an open reading frame of 400 amino acids, a
      poly(A) signal, and a poly(A) tail. We found 100% identity between the 5' part of
      the consensus sequence and the 598-bp-long sequence named TFG. The TFG sequence
      is fused to the 3' end of NTRK1, generating the TRK-T3 fusion transcript found in
      papillary thyroid carcinoma. The cDNA therefore represents the full-length
      transcript of the TFG gene. TFG was localized to 3q11-q12 by fluorescence in situ
      hybridization. The 3' and the 5' ends of the TFG cDNA probe hybridized to a 2.2
      kb band on Northern blot filters in all tissues examined.

PMID- 9169130
TI  - Genetic modifiers of Leprfa associated with variability in insulin production and
      susceptibility to NIDDM.
AB  - In an attempt to identify the genetic basis for susceptibility to non-insulin
      dependent diabetes mellitus within the context of obesity, we generated 401
      genetically obese Leprfa/Leprfa F2 WKY13M intercross rats that demonstrated wide
      variation in multiple phenotypic measures related to diabetes, including plasma
      glucose concentration, percentage of glycosylated hemoglobin, plasma insulin
      concentration, and pancreatic islet morphology. Using selective genotyping genome
      scanning approaches, we have identified three quantitative trait loci (QTLs) on
      Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass
      index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for
      genotype effect on plasma glucose concentration). The obese F2 progeny
      demonstrated sexual dimorphism for these traits, with increased diabetes
      susceptibility in the males appearing at approximately 6 weeks of age, as sexual
      maturation occurred. For each of the QTLs, the linked phenotypes demonstrated
      sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a
      region vicinal to that previously linked to adiposity in studies of diabetes
      susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely
      related to the Wistar counterstrain we employed. Several candidate genes,
      including tubby (tub), multigenic obesity 1 (Mob1), adult obesity and diabetes
      (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous
      to the QTL region identified on rat Chr. 1.

PMID- 9169131
TI  - Construction of a 5-Mb YAC contig from the putative 10q25 tumor-suppressor region
      for glioblastomas.
AB  - During the final step of the malignant progression to glioblastoma multiforme
      (GBM), the most frequent and malignant of primary brain tumors, more than 90% of
      the cases exhibit loss of genetic material on chromosome 10. We previously
      identified a 4-cM deletion interval in the 10q24-qter region that is common to
      all the GBM we have examined. A contig of 20 YACs spanning the 5 Mb of
      chromosomal DNA in the region has been assembled. Overlaps between YACs have been
      verified by STS content, fingerprinting analysis, and/or Alu-Alu PCR. The contig
      contains 17 known microsatellite markers, 15 new STSs derived from the insert
      ends of YACs, 9 ESTs, and 11 others STSs, for a total of 52 STSs (average marker
      density 1/100 kb). The physical map of this region will facilitate the search for
      a candidate tumor-suppressor gene(s) that is inactivated during the information
      of GBM.

PMID- 9169132
TI  - Testis-specific expression of a functional retroposon encoding glucose-6
      phosphate dehydrogenase in the mouse.
AB  - The X-chromosomal gene glucose-6-phosphate dehydrogenase (G6pd) is known to be
      expressed in most cell types of mammalian species. In the mouse, we have detected
      a novel gene, designated G6pd-2, encoding a G6PD isoenzyme. G6pd-2 does not
      contain introns and appears to represent a retroposed gene. This gene is uniquely
      transcribed in postmeiotic spermatogenic cells in which the X-encoded G6pd gene
      is not transcribed. Expression of the G6pd-2 sequence in a bacterial system
      showed that the encoded product is an active enzyme. Zymogramic analysis
      demonstrated that recombinant G6PD-2, but not recombinant G6PD-1 (the X
      chromosome-encoded G6PD), formed tetramers under reducing conditions. Under the
      same conditions, G6PD tetramers were also found in extracts of spermatids and
      spermatozoa, indicating the presence of G6pd-2-encoded isoenzyme in these cell
      types. G6pd-2 is one of the very few known expressed retroposons encoding a
      functional protein, and the presence of this gene is probably related to X
      chromosome inactivation during spermatogenesis.

PMID- 9169133
TI  - A novel myosin-like protein (myocilin) expressed in the connecting cilium of the
      photoreceptor: molecular cloning, tissue expression, and chromosomal mapping.
AB  - We have isolated a human cDNA clone encoding a novel acidic protein of MW 55,000
      that we designated "myocilin" since it has homology to myosin and is localized
      preferentially in the ciliary rootlet and basal body of the connecting cilium of
      photoreceptor cells. The deduced amino acid sequence of human myocilin showed
      significant homologies with nonmuscle myosin of Dictyostelium discoideum in the N
      terminal region and also with olfactomedin of bullfrog in the C-terminal region.
      Myocilin contained a leucine zipper-like motif similar to that seen in kinectin
      and other cytoskeletal proteins. These findings suggest that myocilin is a novel
      cytoskeletal protein involved in the morphogenesis of ciliated neuroepithelium
      such as photoreceptor cells. The myocilin gene (MYOC) was mapped to human
      chromosome 1q23-q24 by fluorescence in situ hybridization.

PMID- 9169134
TI  - Molecular cloning of the interleukin-1 gene cluster: construction of an
      integrated YAC/PAC contig and a partial transcriptional map in the region of
      chromosome 2q13.
AB  - Genes of the interleukin-1 (IL-1) gene cluster localized on chromosome 2q13 are
      implicated in many physiological and pathophysiological processes. We present
      here a high-resolution physical map of this region between markers D2S2008 and
      D2S4/PAX8. An integrated YAC/PAC contig and a partial transcriptional map were
      constructed by STS-constent mapping using the CEPH YAC library and three PAC
      libraries. A total of 3 YACs, 34 PACs, and 56 STSs were integrated: 33 newly
      generated probes to PAC end sequences, 9 polymorphic and 4 nonpolymorphic
      markers, 5 known genes, 4 expressed sequence tags, and 1 pseudogene. Within the
      map, a complete PAC contig of > 1 Mb encompasses the IL-1 gene cluster and PAX8,
      a paired-box-containing gene. This allowed us to define the transcriptional
      orientation of GLVR1, IL1B, and IL1RN and to show that PAX8 is localized outside
      the IL-1 gene cluster. FISH analysis localized PAC clones containing the IL-1
      gene cluster to 2q12-q13. The data provide the basis for further characterization
      of the IL-1 gene cluster and for the construction of a sequence-ready PAC contig
      of this region.

PMID- 9169135
TI  - Mapping individual cosmid DNAs by direct AFM imaging.
AB  - Individual cosmid clones have been restriction mapped by directly imaging, with
      the atomic force microscope (AFM), a mutant EcoRI endonuclease site-specifically
      bound to DNA. Images and data are presented that locate six restriction sites,
      predicted from gel electrophoresis, on a 35-kb cosmid isolated from mouse
      chromosome 7. Measured distances between endonuclease molecules bound to lambda
      DNA, when compared to known values, demonstrate the accuracy of AFM mapping to
      better than 1%. These results may be extended to identify other important site
      specific protein-DNA interactions, such as transcription factor and mismatch
      repair enzyme binding, difficult to resolve by current techniques.

PMID- 9169136
TI  - A 1.7-megabase sequence-ready cosmid contig covering the TSC1 candidate region in
      9q34.
AB  - The disease gene TSC1 has been genetically mapped to human chromosome region
      9q34, in a 4-cM interval between the markers D9S149 and D9S114. Within this
      interval there is conflicting genetic evidence as to the finer localization of
      the gene. We have used finger-printing methods and hybridization to produce a 1.7
      Mb overlapping clone map covering the TSC1 candidate region, with a single gap of
      20 kb. We have localized 12 previously cloned genes and 17 genetic markers on
      this map and have confirmed the order of the genetic map. This deep set of
      overlapping clones is now ready to be used for candidate gene isolation, for
      transcription studies, or for sequencing.

PMID- 9169137
TI  - FKHL15, a new human member of the forkhead gene family located on chromosome
      9q22.
AB  - FKHL15 was isolated from a cDNA library enriched for transcripts from 9q22.
      Isolation and sequencing of a 3.5-kb cDNA clone identified a putative 376-amino
      acid protein with greater than 80% homology over a 100-amino-acid stretch to the
      forkhead DNA-binding domain. The FKHL15 gene contains a region rich in alanine
      residues, frequently associated with transcriptional repression. The forkhead
      genes are believed to play important roles in development and differentiation in
      many different organisms and have also been implicated in the development of some
      tumors. The map position of FKHL15 on 9q22 places the gene within the candidate
      regions for the cancer predisposition syndrome multiple self-healing squamous
      epitheliomata and the degenerative neurological disorder hereditary sensory
      neuropathy type I. This is a region frequently lost in squamous cell cancer.

PMID- 9169138
TI  - Molecular cloning of a novel human gene encoding a 63-kDa protein and its
      sublocalization within the 11q13 locus.
AB  - A human cDNA previously isolated by virtue of its ability to complement partially
      the ultraviolet sensitivity of a xeroderma pigmentosum cell line was further
      characterized. The transcription unit is expressed as a single 4.0-kb mRNA that
      encodes a novel 63-kDa cytoplasmic protein, possibly initiating from an internal
      AUG codon. The gene encoding this protein, named UVRAG, has been extremely well
      conserved during evolution, implying an important role for this gene product in
      cell metabolism. The transcribed mRNA is constitutively expressed in a wide
      variety of human tissues. The protein encoded by this gene is predicted to
      contain a coiled-coil structure and is likely to be metabolically unstable based
      on the occurrence of a strong PEST domain. UVRAG was assigned to human chromosome
      11 by Southern hybridization to a somatic cell hybrid panel. Fluorescence in situ
      hybridization coupled with PCR analysis of human/rodent somatic cell hybrids
      containing segments of human chromosome 11 has localized this gene to a subregion
      of 11q13 in between the D11S916 and the D11S906 loci. Importantly, this region
      has been shown to be amplified in a variety of human malignancies, including
      breast cancer.

PMID- 9169139
TI  - The Cmv1 host resistance locus is closely linked to the Ly49 multigene family
      within the natural killer cell gene complex on mouse chromosome 6.
AB  - Natural killer (NK) cells play important roles in controlling tumor cells and
      against a range of infectious organisms. Recent studies of mouse NK cell surface
      receptors, which may be involved in the specificity of NK cells, have shown that
      many of these molecules are encoded by the Ly49 and Ly55 (Nkrp1) multigene
      families that map to distal mouse chromosome 6. Also mapping to this NK cell gene
      complex (NKC) is the resistance locus, Cmv1, which is involved in genetically
      determined resistance to murine cytomegalovirus (MCMV). The aim of this study was
      to localize Cmv1 more precisely in relation to other NKC loci by generating a
      high-resolution genetic map of the region. We have analyzed 1250 backcross mice
      comprising panels of 700 (BALB/c x C57BL/6J)F1 x BALB/c and 550 (A/J x
      C57BL/6J)F1 x A/J progeny. A total of 25 polymorphic genes or microsatellite
      markers were analyzed over a region of 10 map units from D6Mit134 to D6Mit59. The
      Cmv1 phenotypes of mice recombinant in this interval were tested by infection
      with MCMV. The results obtained indicate that the functionally important NKC
      region is a tightly linked cluster of loci spanning at least 0.4 map units.
      Furthermore, Cmv1 maps distal to, but very closely linked to, the Ly49 multigene
      family (< 0.2 map units), suggesting that MCMV resistance may be conferred by MHC
      class I-specific NK cell receptors.

PMID- 9169140
TI  - Molecular characterization of human neogenin, a DCC-related protein, and the
      mapping of its gene (NEO1) to chromosomal position 15q22.3-q23.
AB  - Neogenin was first identified in the chick embryo, and like a number of cell
      surface proteins of the immunoglobulin (Ig) superfamily, including N-CAM and L1
      (generally called cell adhesion molecules or CAMs), it is expressed on growing
      nerve cells in the developing nervous system of vertebrate embryos. Neogenin is
      also expressed in other embryonic tissues, suggesting a more general role in
      developmental processes such as tissue growth regulation, cell-cell recognition,
      and cell migration. Neogenin, unlike the CAMs, is closely related to a unique
      tumor suppressor candidate molecule, deleted in colorectal carcinoma (DCC). Like
      DCC, the neogenin protein consists of four immunoglobulin-like (Ig-like) domains
      followed by six fibronectin type III domains, a transmembrane domain, and an
      intracellular domain. We now report the cloning and sequencing of cDNA clones
      coding for the human neogenin protein. Human neogenin shares 87% identity with
      its chicken homolog, and like its chicken counterpart it is expressed in at least
      two different isoforms derived from alternative splicing in the intracellular
      domain. Northern blot analysis revealed two mRNA species of about 5 and 7 kb. The
      chromosomal location of the human neogenin gene (HGMW-approved symbol NEO1) was
      determined as 15q22.3-q23, using fluorescence in situ hybridization. The gene
      therefore maps in the vicinity of a locus associated with Bardet-Biedl syndrome.
      The identification of human neogenin and its chromosomal location provides a
      basis for studying its involvement in genetic disorders or diseases.

PMID- 9169141
TI  - The candidate sex-reversing DAX1 gene is autosomal in marsupials: implications
      for the evolution of sex determination in mammals.
AB  - The human X-linked DAX1 gene was cloned from the region of the short arm of the
      human X found in duplicate in sex-reversed Xdup Y females (E. Zanaria et al.,
      1994, Nature 372: 635-641). DAX1 is suggested to be required for ovarian
      differentiation and to play an important role in mammalian sex determination or
      differentiation pathways. Its proposed dose-dependent effect on sexual
      development suggests that DAX1 could represent an evolutionary link with an
      ancestral sex-determining mechanism that depended on the dosage of an X-linked
      gene. Furthermore, DAX1 could also represent the putative X-linked switch gene,
      which independently controls sexual dimorphisms in marsupial mammals in an X-dose
      dependent manner (D.W. Cooper et al., 1993, Semin. Dev. 4: 117-128). If DAX1 has
      a present role in marsupial sexual differentiation or had an ancestral role in
      mammalian sex determination, it would be expected to lie on the marsupial X
      chromosome, despite the autosomal localization of other human Xp genes. We
      therefore cloned and mapped the DAX1 gene in the tammar wallaby (Macropus
      eugenii). DAX1 was located on wallaby chromosome 5p near other human Xp genes,
      indicating that it was originally autosomal and that it is not involved in X
      linked dose-dependent sex determination in an ancestral mammal nor in marsupial
      sexual differentiation.

PMID- 9169142
TI  - A novel SH3-containing human gene family preferentially expressed in the central
      nervous system.
AB  - The Src-homology-3 domain (SH3) is an evolutionarily conserved, 50- to 60-amino
      acid module carried by intracellular proteins involved in the transduction of
      signals for cell polarization, motility, enzymatic activation, and
      transcriptional regulation. The SH3 drives protein-protein interactions through
      binding to proline-rich ligands. This function relies on the conserved secondary
      structure, whereas the SH3 primary structure is highly diverse. Taking advantage
      of the fact that the few conserved amino acids are clustered near the N- and C
      terminal ends, we designed degenerate oligonucleotides spanning these two regions
      and screened by PCR a variety of normal and tumor tissues for the expression of
      SH3-containing transcripts. Using this strategy, we have identified a novel SH3
      containing human gene family of six related transcripts that map to four
      different chromosomes. The SH3 domain lies at the C-terminal end and shows 56-50%
      amino acid homology to the C-terminal SH3 of Sem-5/Drk/GRB2. The N-terminal
      segment of this novel SH3GL (from SH3-containing Grb2-like) gene family does not
      resemble any known protein. Three of these transcripts are in-frame and show a
      peculiar tissue distribution: SH3GL2 is preferentially expressed in the brain,
      SH3GL3 in brain and testis, and SH3GL1 is ubiquitous.

PMID- 9169143
TI  - Characterization of the human and rat phospholemman (PLM) cDNAs and localization
      of the human PLM gene to chromosome 19q13.1.
AB  - Previous reports have demonstrated that the phospholemman (PLM), a 72-residue
      plasma-membrane protein enriched in skeletal muscle and heart, is a major
      substrate phosphorylated in response to insulin and adrenergic stimulation. Here
      we describe the isolation and characterization of human and rat PLM cDNA from the
      heart. Both PLM proteins share significant nucleotide and amino acid sequence and
      structural similarities with the previously published canine PLM and, to a lesser
      degree, with Na+/K(+)-ATPase gamma subunit, Mat-8 protein, and CHIF protein.
      Despite the functional diversity, all these proteins are quite small and possess
      a single transmembrane domain. Human PLM appears to be a unique gene localized on
      chromosome 19q13.1. The PLM mRNA is widely distributed in human tissues, with the
      highest expression in skeletal muscle and heart, suggesting a functional role in
      muscle contraction. Like canine PLM, both human and rat PLM induce a
      hyperpolarization-activated chloride current when expressed in Xenopus oocytes.
      The high degree of sequence and functional conservation among the mammalian PLM
      proteins indicates that this gene is conserved throughout evolution.

PMID- 9169144
TI  - A novel zinc finger-containing RNA-binding protein conserved from fruitflies to
      humans.
AB  - The Drosophila lark gene encodes an essential RNA-binding protein of the RNA
      recognition motif (RRM) class that is required during embryonic development.
      Genetic analysis demonstrates that it also functions as a molecular element of a
      circadian clock output pathway, mediating the temporal regulation of adult
      emergence in the fruitfly. We now report the molecular characterization of a
      human gene with significant similarity to lark. Based on fluorescence in situ
      hybridization and radiation hybrid mapping, the human gene has been localized to
      chromosome region 11q13; it is closely linked to several identified genes
      including the locus of Bardet-Biedl syndrome type 1. The lark-homologous human
      gene expresses a single 1.8-kb size class of mRNA in most or all tissues
      including brain. Additional database searches have identified a mouse counterpart
      that is virtually identical to the human protein. Similar to lark protein, both
      mammalian proteins contain two copies of the RRM-type consensus RNA-binding
      motif. Unlike most RRM family members, however, the Drosophila and mammalian
      proteins also contain a retroviral-type (RT) zinc finger that is situated 43
      residues C-terminal to the second RRM element. Within a 184-residue segment
      spanning the RRM elements and the RT zinc finger, the human and mouse proteins
      are 61% similar to the Drosophila lark sequence. These common sequence features
      and comparisons among a large collection of RRM proteins suggest that the human
      and mouse proteins represent homologues of Drosophila lark.

PMID- 9169145
TI  - Expression and human chromosomal localization to 17q25 of the growth-regulated
      gene encoding the mitochondrial ribosomal protein MRPL12.
AB  - Mitochondrial activity requires the expression of nuclear genes, whose products
      are part of multiproteic complexes leading to ATP production and delivery. We
      recently characterized a growth-activated mRNA encoding the human mitochondrial
      ribosomal MRPL12 protein, which is thought to act as a translational regulator of
      mitochondrial mRNAs. We show here that MRPL12 mRNA expression is enhanced in
      growth-stimulated cells as a result of transcriptional activation, a feature lost
      in transformed cell lines. MRPL12 mRNA is highly expressed in the colon, in which
      a reduction in mitochondrial activity was shown to be associated with tumor
      formation. The human MRPL12 protein is encoded by a unique gene located on
      chromosome 17 (q25-qter). As no predisposition to colon cancer linked to this
      chromosomal region was hitherto reported, the MRPL12 gene might be involved in
      the process of differentiation of colonic epithelial cells.

PMID- 9169146
TI  - Cloning and characterization of an alternatively spliced gene in proximal Xq28
      deleted in two patients with intersexual genitalia and myotubular myopathy.
AB  - We have identified a novel human gene that is entirely deleted in two boys with
      abnormal genital development and myotubular myopathy (MTM1). The gene, F18, is
      located in proximal Xq28, approximately 80 kb centromeric to the recently
      isolated MTM1 gene. Northern analysis of mRNA showed a ubiquitous pattern and
      suggested high levels of expression in skeletal muscle, brain, and heart. A
      transcript of 4.6 kb was detected in a range of tissues, and additional alternate
      forms of 3.8 and 2.6 kb were present in placenta and pancreas, respectively. The
      gene extends over 100 kb and is composed of at least seven exons, of which two
      are noncoding. Sequence analysis of a 4.6-kb cDNA contig revealed two overlapping
      open reading frames (ORFs) that encode putative proteins of 701 and 424 amino
      acids, respectively. Two alternative spliced transcripts affecting the large open
      reading frame were identified that, together with the Northern blot results,
      suggest that distinct proteins are derived from the gene. No significant homology
      to other known proteins was detected, but segments of the first ORF encode
      polyglutamine tracts and proline-rich domains, which are frequently observed in
      DNA-binding proteins. The F18 gene is a strong candidate for being implicated in
      the intersexual genitalia present in the two MTM1-deleted patients. The gene also
      serves as a candidate for other disorders that map to proximal Xq28.

PMID- 9169147
TI  - An integrated genetic and physical map of the autosomal recessive polycystic
      kidney disease region.
AB  - Autosomal recessive polycystic kidney disease is one of the most common
      hereditary renal cystic diseases in children. Genetic studies have recently
      assigned the only known locus for this disorder, PKHD1, to chromosome 6p21-p12.
      We have generated a YAC contig that spans approximately 5 cM of this region,
      defined by the markers D6S1253-D6S295, and have mapped 43 sequence-tagged sites
      (STS) within this interval. This set includes 20 novel STSs, which define 12
      unique positions in the region, and three ESTs. A minimal set of two YACs spans
      the segment D6S465-D6S466, which contains PKHD1, and estimates of their sizes
      based on information in public databases suggest that the size of the critical
      region is < 3.1 Mb. Twenty-eight STSs map to this interval, giving an average STS
      density of < 1/150 kb. These resources will be useful for establishing a complete
      transcription map of the PKHD1 region.

PMID- 9169148
TI  - Human sulfotransferase SULT1C1: cDNA cloning, tissue-specific expression, and
      chromosomal localization.
AB  - We have isolated and sequenced a cDNA that encodes an apparent human orthologue
      of a rat sulfotransferase (ST) cDNA that has been referred to as "ST1C1"-although
      it was recently recommended that sulfotransferase proteins and cDNAs be
      abbreviated "SULT." The new human cDNA was cloned from a fetal liver-spleen cDNA
      library and had an 888-bp open reading frame. The amino acid sequence of the
      protein encoded by the cDNA was 62% identical with that encoded by the rat ST1C1
      cDNA and included signature sequences that are conserved in all cytosolic SULT
      enzymes. Dot blot analysis of mRNA from 50 human tissues indicated that the cDNA
      was expressed in adult human stomach, kidney, and thyroid, as well as fetal
      kidney and liver. Northern blot analyses demonstrated that the major SULT1C1 mRNA
      in those same tissues was 1.4 kb in length. We next determined the partial human
      SULT1C1 gene sequence for a portion of the 5'-terminus of one intron. That
      sequence was used to design SULT1C1 gene-specific primers that were used to
      perform the PCR with DNA from human/rodent somatic cell hybrids to demonstrate
      that the gene was located on chromosome 2. PCR amplifications performed with
      human chromosome 2/rodent hybrid cell DNA as template sublocalized SULT1C1 to a
      region between bands 2q11.1 and 2q11.2.

PMID- 9169149
TI  - Genomic organization, complete sequence, and chromosomal location of the gene for
      human eotaxin (SCYA11), an eosinophil-specific CC chemokine.
AB  - Eotaxin is a CC chemokine that is a specific chemoattractant for eosinophils and
      is implicated in the pathogenesis of eosinophilic inflammatory diseases, such as
      asthma. We describe the genomic organization, complete sequence, including 1354
      bp 5' of the RNA initiation site, and chromosomal localization of the human
      eotaxin gene. Fluorescence in situ hybridization analysis localized eotaxin to
      human chromosome 17, in the region q21.1-q21.2, and the human gene name SCYA11
      was assigned. We also present the 5' flanking sequence of the mouse eotaxin gene
      and have identified several regulatory elements that are conserved between the
      murine and the human promoters. In particular, the presence of elements such as
      NF-kappa B, interferon-gamma response element, and glucocorticoid response
      element may explain the observed regulation of the eotaxin gene by cytokines and
      glucocorticoids.

PMID- 9169150
TI  - Genomic structure and chromosomal localization of GML (GPI-anchored molecule-like
      protein), a gene induced by p53.
AB  - Among its known functions, tumor suppressor gene p53 serves as a transcriptional
      regulator and mediates various signals through activation of downstream genes. We
      recently identified a novel gene, GML (glycosylphosphatidylinositol (GPI)
      anchored molecule-like protein), whose expression is specifically induced by
      wildtype p53. To characterize the GML gene further, we determined 35.8 kb of DNA
      sequence that included a consensus binding sequence for p53 and the entire GML
      gene. The GML gene consists of four exons; and the p53-binding sequence is
      present in the 5'-flanking region. In genomic organization this gene resembles
      genes encoding murine Ly-6 glycoproteins, a human homologue of the Ly-6 family
      called RIG-E, and CD59; products of these genes, known as GPI-anchored proteins,
      are variously involved in signal transduction, cell-cell adhesion, and cell
      matrix attachment. FISH analysis revealed that the GML gene is located on human
      chromosome 8q24.3. Genes encoding at least two other GPI-anchored molecules, E48
      and RIG-E, are also located in this region.

PMID- 9169151
TI  - Localization and characterization of the human ADP-ribosylation factor 5 (ARF5)
      gene.
AB  - ADP-ribosylation factor 5 (ARF5) is a member of the ARF gene family. The ARF
      proteins stimulate the in vitro ADP-ribosyltransferase activity of cholera toxin
      and appear to play a role in vesicular trafficking in vivo. We have mapped ARF5,
      one of the six known mammalian ARF genes, to a well-defined yeast artificial
      chromosome contig on human chromosome 7q31.3. In addition, we have isolated and
      sequenced an approximately 3.2-kb genomic segment that contains the entire ARF5
      coding region, revealing the complete intron-exon structure of the gene. With six
      coding exons and five introns, the genomic structure of ARF5 is unique among the
      mammalian ARF genes and provides insight about the evolutionary history of this
      ancient gene family.

PMID- 9169152
TI  - Aphidicolin-induced FRA3B breakpoints cluster in two distinct regions.
AB  - The common fragile site at chromosomal band 3p14.2 (FRA3B) is the most sensitive
      single site in the human genome to induced chromosomal lesions. This fragile site
      may predispose chromosome 3p to breakage that is commonly observed in lung,
      renal, and many other cancers. We previously used aphidicolin induction of FRA3B
      expression in a chromosome 3-only somatic cell hybrid to generate a series of
      hybrids with breakpoints in the 3p14.2 region. These breakpoints were localized
      to two distinct clusters, separated by 200 kb, that lie on either side of a
      region of frequent breakage within FRA3B as observed by FISH analysis. Seven
      proximal aphidicolin-induced breakpoints were localized at or near the end of a
      THE element. The THE-1 element is flanked by LINE and Alu repetitive elements.
      The eight distal aphidicolin-induced breakpoints clustered in a region capable of
      forming multiple hairpin-like structures. Thus repetitive elements and hairpin
      like structures may be responsible for chromosome fragility in this region.

PMID- 9169153
TI  - Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes
      reveals conservation of their gene and protein structures.
AB  - The very recently found evolutionarily conserved DNA-binding domain of 100 amino
      acids, termed the fork head domain, emerged from a sequence comparison of the rat
      hepatocyte transcription factor HNF-3 alpha and the homeotic gene fork head of
      Drosophila. We previously isolated a new member of this family, the mesenchyme
      fork head-1 (MFH-1) gene, which is expressed in developing mesenchyme. Here we
      describe the isolation of the mouse (MFH-1) and human (FKHL14) chromosomal MFH-1
      genes and the determination of the gene and protein structures of MFH-1. We found
      that the MFH-1 gene has no introns and that the identity of the amino acid
      sequences of mouse and human MFH-1 proteins is 94%. We also investigated the
      transcriptional activity of the mouse and human MFH-1 proteins and found that
      both proteins act as positive transactivators.

PMID- 9169154
TI  - Chromosomal localization of the human and mouse hyaluronan synthase genes.
AB  - We have recently identified a new vertebrate gene family encoding putative
      hyaluronan (HA) synthases. Three highly conserved related genes have been
      identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in
      the mouse. All three genes encode predicted plasma membrane proteins with
      multiple transmembrane domains and approximately 25% amino acid sequence identity
      to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any
      one HAS gene in transfected mammalian cells leads to high levels of HA
      biosynthesis. We now report the chromosomal localization of the three HAS genes
      in human and in mouse. The genes localized to three different positions within
      both the human and the mouse genomes. HAS1 was localized to the human chromosome
      19q13.3-q13.4 boundary and Has1 to mouse Chr 17.HAS2 was localized to human
      chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human
      chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces
      the recently reported relationship between a small region of human chromosome 19q
      and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical
      region delineated for the Langer-Giedion syndrome and can thus be excluded as a
      candidate gene for this genetic syndrome.

PMID- 9169155
TI  - Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved
      linkage groups on mouse chromosomes 3 and 8.
AB  - Npy1r and Npy2r, the genes encoding mouse type 1 and type 2 neuropeptide Y
      receptors, have been mapped by interspecific backcross analysis. Previous studies
      have localized the human genes encoding these receptors to chromosome 4q31-q32.
      We have now assigned Npy1r and Npy2r to conserved linkage groups on mouse Chr 8
      and Chr 3, respectively, which correspond to the distal region of human
      chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance
      between the human genes to be approximately 6 cM. Although ancient tandem
      duplication events may account for some closely spaced G-protein-coupled receptor
      genes, the large genetic distance between the human type 1 and type 2
      neuropeptide Y receptor genes raises questions about whether this mechanism
      accounts for their proximity.

PMID- 9169156
TI  - Assignment of the human stress-activated protein kinase-3 gene (SAPK3) to
      chromosome 22q13.3 by fluorescence in situ hybridization.

PMID- 9169157
TI  - Molecular cloning and mapping of a novel human KRAB domain-containing C2H2-type
      zinc finger to chromosome 7q36.1.

PMID- 9169158
TI  - Ethnic differences in uterine corpus cancer incidence and mortality in New
      Mexico's American Indians, hispanics and non-Hispanic whites.
AB  - BACKGROUND: Although ethnic and radical differences in uterine corpus cancer
      incidence and mortality have been reported worldwide, few published data have
      addressed the epidemiology of uterine cancer among US American Indians and
      Hispanics. METHODS: We reviewed uterine corpus cancer incidence and survival data
      from New Mexico's population-based cancer registry collected from 1969 to 1992,
      and examined State vital records data for uterine cancer deaths collected from
      1958 to 1992, focusing on ethnic differences in occurrence and outcomes of
      uterine malignancies. RESULTS: Non-Hispanic white women had age-adjusted
      incidence rates that were substantially higher (20.8 per 100,000) than rates for
      Hispanics (10.3) and American Indians (6.0) over the 24-year period. Uterine
      cancer mortality rates were also higher for non-Hispanic whites and Hispanics
      than for American Indian women, although mortality rates were substantially lower
      than incidence rates. Five-year survival for uterine cancer was comparable among
      all groups for all stages combined (87.3% for non-Hispanic whites, 81.4% for
      Hispanics, and 84.6% for American Indians). CONCLUSIONS: Our population-based
      data show ethnic differences in uterine corpus cancer incidence rates for non
      Hispanic white women that were double those for Hispanics, and triple those for
      American Indian women. Ethnic differences in survival were comparable. Aetiologic
      studies are warranted to investigate the dramatic ethnic differences in
      occurrence of uterine cancer.

PMID- 9169159
TI  - Family history of cancer and risk of lung cancer in lifetime non-smokers and long
      term ex-smokers.
AB  - BACKGROUND: Genetic factors appear to play a role in the aetiology of lung
      cancer. METHODS: To examine the association between family history of cancer (all
      types) and risk of lung cancer among non-smokers, we conducted a case-control
      study. Cases (n = 618) were identified through the Missouri Cancer Registry for
      the period 1986 through 1991, and included 432 lifetime non-smokers and 186 ex
      smokers who had stopped at least 15 years prior to diagnosis or had smoked for
      less than one pack-year. Controls (n = 1402) were selected through drivers
      licence and Medicare files. RESULTS: The risk of lung cancer increased directly
      in relation to the number of family members affected with cancer. The odds ratio
      (OR) associated with five or more first-degree relatives with cancer was 2.7 (95%
      confidence interval [CI] 1.2-6.1), with a significant linear trend in risk
      according to the number of relatives affected (P = 0.03). Increased lung cancer
      risk was associated with two or more affected siblings (OR = 1.4; 95% CI: 1.0
      1.9) and with two or more affected offspring (OR = 3.2: 95% CI: 1.3-8.1). Risk
      was slightly elevated for family history of lung cancer (OR = 1.3; 95% CI: 1.0
      1.8). CONCLUSIONS: Our study identified a slight increase in risk of lung cancer
      in relation to five or more relatives with cancer. Preventive implications of
      this increased risk are unclear because the attributable fraction is low in
      comparison to a variety of other factors.

PMID- 9169160
TI  - Are cancers of the salivary gland increasing? Experience from Connecticut, USA.
AB  - BACKGROUND: Recent studies indicate that cancers of the salivary gland are
      increasing, and the factors responsible for the increase are unknown. Artefactual
      changes, such as shift in classifying cancers of the floor of the mouth to
      cancers of the salivary gland, could affect the time trend for salivary gland
      cancer. METHODS: The current study examined the time trends for cancers of the
      salivary gland and for cancers of the floor of the mouth and lower gum by using
      Connecticut Tumor Registry data for the time period 1935-1992. A regression model
      was used to identify the components of birth cohort, period and age as
      determinants of the observed time trend. RESULTS: Cancers of the salivary gland
      have recently increased in Connecticut, with a relative risk of 1.48 (95% CI:
      1.06-2.08) for females in 1990-1992 compared to 1980-1984, and a comparable
      relative risk of 1.60 (95% CI: 1.16-2.22) for males. The increase was found in
      all age groups 40 and over, particularly among those aged 70 and over. The
      results from age-period-cohort modelling show a recent upturn in the trend for
      period slopes, with no clear increase from recent birth cohorts, which is
      consistent with the results from univariate analyses suggesting no clear increase
      among those under 40 years of age. CONCLUSION: Our results suggest that
      artifactual changes, such as a shift in designation of cancer sites, increasing
      use of the needle aspirate biopsies, and greater access to medical care for the
      elderly, may have largely contributed to the rising trend. The known risk
      factors, radiation exposure and a history of a prior cancer, can hardly explain
      the observed increase. The Epstein-Barr virus infection has only been associated
      with certain types of rare squamous cell carcinomas of the salivary gland in the
      Eskimo population. The AIDS epidemic also cannot explain why older age groups
      have accounted for most of the increase in incidence of the disease. An
      examination of the incidence rates for cancers of the salivary gland from other
      populations may help to clarify the issue.

PMID- 9169161
TI  - Growth and development and other risk factors for osteosarcoma in children and
      young adults.
AB  - BACKGROUND: Risk factors for osteosarcoma in young people were investigated in a
      population-based case-control study among residents of New York State, excluding
      New York City. METHODS: Cases (n = 130) were diagnosed between 1978 and 1988 at <
      or = 24 years of age. Controls were randomly selected from birth certificates and
      were pair matched to cases on year of birth and sex. Exposure information was
      obtained by telephone interview with a subject and/or parent, and from birth
      certificates and school and medical records. RESULTS AND CONCLUSIONS: A
      significant positive association was observed with height one year before
      diagnosis (P-value for trend = 0.02). No significant associations were observed
      between osteosarcoma and weight of body mass index one year before diagnosis,
      birth length, birthweight, gestational age, having reached puberty, having begun
      growth spurt, age at puberty, age growth spurt began, medical x-rays, antenatal
      exposures, family history of cancer, birth defects, or parental occupation.

PMID- 9169162
TI  - The influence of country of birth on mortality from all causes and cardiovascular
      disease in Sweden 1979-1993.
AB  - BACKGROUND: Epidemiological data on ethnicity and health in Sweden have mostly
      been derived from small populations and focused on morbidity. The present study
      highlights the relation between country of birth, adjusted for other social
      variables, and total mortality and mortality from circulatory diseases and
      coronary heart disease (CHD). METHODS: The interviews with 21,420 males and
      21,977 females aged 20-74 were conducted during a 7-year period, 1979-1985. The
      data consist of seven independent samples of the Swedish population. The present
      investigation was designed as a longitudinal follow-up study ranging from the day
      of the interview to 31 December 1993. Mortality data were obtained from the Cause
      of Death Register based on the Swedish national registration number. Person-years
      at risk were calculated from the date of the interview until death, or for those
      who survived, until the end of the follow-up period. The data were analysed by
      sex, using a proportional hazard model. RESULTS: Men born in Finland had an
      increased mortality from all causes of death. Women born in Finland had an
      increased mortality risk for circulatory diseases with a relative risk (RR) of
      2.15 (95% confidence interval [CI] : 1.45-3.20) when adjusted for age, marital
      status, form of housing tenure and years of education. The relationship between
      being a woman born in Finland or Eastern Europe and mortality for coronary heart
      disease (CHD) was significant with an RR of 2.18 (95% CI : 1.24-3.81) and 3.02
      (95% CI : 1.24-7.34) respectively. The form of housing tenure was significantly
      associated with mortality in all models. Education showed a graded relation to
      total mortality and to mortality from circulatory diseases and CHD. CONCLUSIONS:
      The increased mortality risk for Finnish males and females and, in addition the
      increased circulatory disease mortality risk for Finnish females and the strongly
      increased risk for CHD mortality for females born in Finland and Eastern Europe
      could not be explained by confounding by age, marital status or socioeconomic
      position.

PMID- 9169163
TI  - Serum uric acid and its correlates in Chinese adult populations, urban and rural,
      of Beijing. The PRC-USA Collaborative Study in Cardiovascular and Cardiopulmonary
      Epidemiology.
AB  - BACKGROUND: Reports on serum uric acid (SUA) levels in Chinese populations are
      sparse, but there is evidence that hyperuricaemia and gout are not uncommon. This
      paper characterizes SUA levels, their correlates, and their relationship to blood
      pressure (BP) and prevalent high blood pressure (HBP) for urban and rural adult
      population samples in north China. METHODS: In 1987-1988, a cross-sectional study
      was carried out, using standardized methods, on men and women aged 40.58 in a
      Beijing area urban steel mill (N = 2013) and on rural farms (1507). Main outcome
      measures were SUA, systolic and diastolic blood pressure (SBP, DBP), and
      prevalent HBP (SBP > or = 140 or DBP > or = 90 mmHg or receiving an
      antihypertensive drug). RESULTS: Mean SUA levels for men were 5.75 mg/dl in urban
      and 5.58 mg/dl in rural settings; for women, 4.67 and 4.48 mg/dl. Mean values
      were higher with age in women, but not in men. Age-standardized prevalence rates
      of HBP were significantly higher in upper SUA strata (men > or = 7.00, women > or
      = 6.00 mg/dl) than lower SUA strata both with and without inclusion of those on
      antihypertensive drugs. Mean SUA levels were correspondingly higher in
      hypertensive than non-hypertensive people. In multiple regression analyses, body
      mass index and serum triglycerides were strongly associated with SUA. Also SBP,
      DBP, and HBP were generally associated with SUA for the whole population sample,
      with smaller coefficients after excluding those on antihypertensive drugs.
      However, in these multivariate analyses the strength of the association was low
      order. CONCLUSION: In addition to its strong association with body mass index,
      SUA is independently related to serum lipids, particularly triglycerides, and to
      serum glucose. While some of the univariate relation of SUA to BP is apparently
      due to the strong relation of body mass to both SUA and BP, a low order
      significant relation between SUA and BP remains with control for BMI.

PMID- 9169164
TI  - The association of modernization with dyslipidaemia and changes in lipid levels
      in the Polynesian population of Western Samoa.
AB  - BACKGROUND: Obesity and non-insulin-dependent diabetes mellitus (NIDDM) have
      increased in prevalence in Polynesian Western Samoans over the 13-year period
      1978-1991, as the population undergoes an 'epidemiological transition'. METHODS:
      We therefore investigated changes in the frequency of dyslipidaemia over the same
      period in adults aged 25-74 years, and examined factors associated with
      dyslipidaemia in cross-sectional and longitudinal data. Subjects were drawn from
      three geographically defined locations representing different degrees of
      modernization. RESULTS: The age-standardized prevalence of dyslipidaemia
      increased in each location between 1978 (n = 1197) and 1991 (n = 1748) with the
      prevalence of hypercholesterolaemia (> or = 5.5 mmol/l) increasing from 18% to
      36% (P < 0.001), and that of hypertriglyceridaemia (> or = 2.0 mmol/l) increasing
      from 9% to 15% (P < 0.001) in the capital city, Apia. In 1991 the highest serum
      concentrations of total, high density lipoprotein (HDL) and calculated low
      density lipoprotein (LDL) cholesterol were found in Poutasi (intermediate level
      of modernization), and the highest triglyceride levels in urbanized Apia. Higher
      levels of body mass index (BMI), waist-hip ratio (WHR), glucose intolerance,
      fasting insulin concentration, physical inactivity, educational level, and
      occupational status were all associated with adverse lipid levels in univariate
      data. Obesity (BMI in women, WHR in men) and survey location were the most
      important correlates of abnormal lipid levels in logistic regression models.
      Fasting insulin was also independently associated with high triglyceride levels
      in men, while in women the increasing levels of fasting insulin were associated
      with adverse levels of total, LDL and HDL cholesterol, and triglycerides. In
      longitudinal data (n = 311), lower baseline levels of cholesterol and
      triglycerides were associated with greater increases in either parameter at
      follow-up. Elevated fasting insulin and female gender also predicted increasing
      cholesterol concentrations, and urban residence predicted an increase in
      triglyceride levels. CONCLUSIONS: Current levels of dyslipidaemia in Western
      Samoa are similar to those observed in developed Western populations, and are
      increasing rapidly. These findings, considered along with the high prevalence of
      other cardiovascular disease risk factors in Samoans, including smoking, obesity
      and NIDDM, suggest that cardiovascular disease will be a major health concern in
      the future.

PMID- 9169165
TI  - Relationship of alcohol use, physical activity and dietary habits with serum
      carotenoids, retinol and alpha-tocopherol among male Japanese smokers.
AB  - BACKGROUND: Despite considerable interest in the anticarcinogenic and anti
      atherosclerotic effects of carotenoids and alpha-tocopherol, little is known
      about determinants of these serum micronutrients. METHODS: The association of
      lifestyle factors including alcohol use, physical activity and dietary habits
      with serum levels of carotenoids (lycopene, lutein, cryptoxanthin and beta
      carotene), retinol and alpha-tocopherol were studied in 194 healthy men aged 24
      60 years who smoked > 15 cigarettes/day. A self-administered questionnaire
      ascertained consumption frequency of 12 food items, alcohol consumption, levels
      of physical activity and the number of cigarettes smoked per day. RESULTS: Of the
      dietary items studied, total vegetable intake was significantly, positively
      associated with beta-carotene levels, as was fruit intake with serum levels of
      each carotenoid. Tofu intake was unexpectedly, but strongly related to decreased
      levels of cryptoxanthin and beta-carotene. None of the food items was materially
      related to serum levels of retinol and alpha-tocopherol. Alcohol consumption was
      most strongly and inversely associated with levels of all the carotenoids except
      lutein, whereas was positively associated with retinol level but not with alpha
      tocopherol level. Frequency of participation in sports was significantly and
      positively associated with both retinol and alpha-tocopherol levels. The amount
      of cigarettes smoked per day was unrelated to each micronutrient level in this
      study of moderate or heavy smokers. CONCLUSIONS: The consumption of vegetables
      and fruits is an important determinant of serum carotenoid levels even in
      smokers. Alcohol consumption is inversely associated with carotenoid levels,
      although the mechanism for this is not clear. Tofu and physical activity
      influence serum levels of antioxidative micronutrients, and these relationships
      need further studies.

PMID- 9169166
TI  - Agreement between self and partner reports of paternal drinking and smoking. The
      ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
AB  - BACKGROUND: We examined agreement between self and proxy reports of paternal
      drinking and smoking behaviour using data collected as part of the prospective,
      population-based Avon (England) Longitudinal Study of Pregnancy and Childhood.
      METHODS: Information on the smoking and drinking habits of pregnant women's male
      partners was obtained through self-administered questionnaires completed by
      pregnant participants and by their partners. For dichotomous indicators (e.g.
      smoker versus non-smoker), we evaluated self/proxy agreement by calculating Kappa
      coefficients and per cent agreement. For ordinal measures of smoking and drinking
      amounts, we calculated per cent perfect agreement, per cent agreement within one
      category, and Spearman correlation coefficients. Data from 8414 respondent pairs
      were included in the analyses. RESULTS: Men's and women's reports of paternal
      smoking and drinking status were in nearly complete agreement (95% and 98%,
      respectively). For analyses of smoking and drinking amounts, agreement within one
      category remained high (90% and 98% for smoking and drinking, respectively), but
      perfect agreement on amount was somewhat lower (81% and 71%, respectively). Per
      cent perfect agreement on smoking amount was especially low (50%) when non
      smokers were excluded. When couples' reports were not in perfect agreement, women
      tended to report lower amounts of smoking and drinking for their partners
      compared to the men's self reports. CONCLUSIONS: Our results suggest that women's
      proxy reports of their partners' drinking and smoking status can be used with
      considerable confidence in reproductive epidemiological studies when the
      enrollment of both women and men as participants is infeasible for financial or
      logistical reasons. Caution is warranted, however, when proxy reports are used
      for more detailed information on smoking and drinking amounts.

PMID- 9169167
TI  - Mortality and morbidity of potentially misclassified smokers.
AB  - OBJECTIVE: Misclassification of smokers as non-smokers may bias estimates of the
      excess morbidity and mortality associated with smoking. The issue has been given
      little, if any, attention in prospective epidemiological studies. This study
      examined characteristics of potentially misclassified smokers with respect to
      mortality, morbidity, and risk factors. METHOD: A prospective study (within The
      Copenhagen Male Study, Denmark) used serum cotinine as an objective marker of use
      of tobacco. A serum concentration of 100 ng/ml was regarded as a relevant
      threshold for active smoking. In all, 3270 males aged 53-74 years who reported
      their previous and current tobacco habits, including the use of chew tobacco and
      snuff, were included. Incidence of all causes of mortality (ACM) during 9 years
      and death due to ischaemic heart disease (IHD) during 8 years of follow-up were
      the main outcome measures. RESULTS: Overall cumulative incidence rates of ACM and
      IHD were 19.1% and 4.3%, respectively. Of 1405 men who reported being non-tobacco
      users, i.e. no current smoking and no use of chewing tobacco or snuff, 1377 had
      levels < 100 ng/ml, 28 men (2%) had levels equal to or above this threshold value
      and were considered potentially misclassified smokers. They had significantly
      higher mortality rates, 35.7% versus 14.7%, P < 0.001, than other self-reported
      non-tobacco users, and a slightly higher prevalence of tobacco-related cancer,
      and a highly significant higher prevalence of myocardial infarction, P < 0.001.
      Compared to non-tobacco users with low cotinine, age-adjusted relative risks (95%
      CI) were 2.4 (1.3-4.5), P < 0.01, for ACM, and 5.3 (95% CI : 2.1-13.4), P <
      0.001, for IHD. CONCLUSIONS: Potentially misclassified smokers deviated strongly
      from other non-smokers with respect to mortality and morbidity. The importance of
      this reporting bias when estimating the risk associated with active or passive
      smoking is discussed.

PMID- 9169169
TI  - Enrollment of a population-based cohort of newborns at higher risk of developing
      a chronic condition: the EDEN study. Etude du Developpement des Nouveau-nes
      Study.
AB  - OBJECTIVE: To describe the methods used at birth to recruit a population-based
      cohort of newborns of all birthweights at higher risk of having a chronic
      condition, and to present baseline results. METHODS: Screening of all newborns at
      hospital discharge for five non-exclusive criteria: (1) low birthweight (LBW),
      (2) congenital anomalies or genetic disease, (3) specified conditions associated
      with a high probability of chronicity, (4) referral to a neonatal intensive care
      unit (NICU), (5) or defined social problems. Calculation of Hobel risk scores for
      children satisfying > or = 1 criterion. SUBJECTS: All 6477 live births delivered
      in the 19 maternity hospitals of a geographically defined region (Vaud,
      Switzerland) to resident mothers in 1993-1994. RESULTS: Twelve per cent (n = 760)
      of newborns met > or = 1 criterion: 6.3% of all newborns had an LBW (criterion
      1), 2.4% had a birth defect, 0.9% met criterion (3), 4.4% stayed in an NICU and
      1.6% had serious social problems. Hobel prenatal score was high (> or = 10
      points) for 41% of children with > or = 1 criterion, the intrapartum score for
      87% and the neonatal score for 68%. CONCLUSIONS: Most newborns identified by the
      above simple criteria also had elevated perinatal risks. The validity of the
      criteria will later be tested against the results of the examinations of children
      with > or = 1 criterion at 18 months and 4 years of age, but the assessment at
      birth already shows that normal birthweight (NBW) children, in agreement with
      previous studies, contribute half the children at high risk perinatally.

PMID- 9169168
TI  - Smoking and Parkinson's disease: a case-control study in Germany.
AB  - BACKGROUND: In a hospital based case-control study, we investigated the role of
      environmental factors in the aetiology of Parkinson's disease. This paper
      describes our results on smoking habits. METHODS: The smoking histories of 380
      Parkinson's disease (PD) patients recruited from nine German clinics were
      compared to those of age- and sex-matched control subjects (379 neighbourhood
      controls and 376 controls from the same region). Detailed information on smoking
      behaviour was collected in structured personal interviews in order to calculate
      the number of pack-years smoked up to the time of diagnosis. Conditional logistic
      regression was used to calculate odds ratios (OR) and control for potential
      confounders. RESULTS: Among PD patients, 44% had ever smoked, as compared to 59%
      in both control groups. Among ever-smoking patients, 74% quit prior to the date
      of diagnosis, as compared to roughly 45% of the ever-smoking control subjects.
      The OR for ever having smoked was 0.5 (95% confidence interval [CI]: 0.3-0.7), P
      trend < 0.00005). CONCLUSIONS: The results are considered in terms of criteria
      for causality. Plausible explanations for the observed inverse association
      between smoking and PD include: 1. A genetic predisposition that increases the
      risk for PD (such as defective detoxification enzymes) simultaneously decreases
      the likelihood of smoking. 2. Inherently lower dopamine levels in predestined PD
      patients cause them to be less prone to addiction. 3. Smoking is neuroprotective.

PMID- 9169170
TI  - Association of breastfeeding and stunting in Peruvian toddlers: an example of
      reverse causality.
AB  - BACKGROUND: Child feeding recommendations include breastfeeding beyond 12 months,
      however, some researchers have reported increased rates of malnutrition in
      breastfed toddlers. A negative association between growth and breast-feeding may
      reflect reverse causality; that is, the outcome (growth) is a determinant of the
      predictor (breastfeeding), and not vice versa. We examined this question with
      data from 134 Peruvian toddlers. METHODS: A linear regression analysis predicted
      length at the age of 15 months by length at 12 months, study interval, and 12
      14.9-month breastfeeding, complementary food intake, and diarrhoeal incidence.
      This analysis defined the association between breastfeeding and linear growth. To
      elucidate the direction of the effect between breastfeeding and linear growth,
      logistic regression was used to predict the probability of weaning by the end of
      14 months. Determinants included weight-for-age (W/A) at 12 months, complementary
      food intake at 9-11.9 months, and change in diarrhoeal incidence between 9 and
      14.9 months. RESULTS: There was a significant (P < 0.01) interaction of
      breastfeeding, diarrhoeal incidence, and complementary food intake on length at
      15 months. Increased breastfeeding was associated with a 1.0 cm decrease in
      length gain when dietary intake was low and diarrhoeal morbidity was high,
      implying that breastfeeding is harmful. The logistic analysis, however,
      demonstrated that the risk of weaning decreased only when W/A and dietary intake
      were low and diarrhoeal morbidity was high. CONCLUSIONS: The negative association
      between breastfeeding and linear growth reflected reverse causality. Increased
      breastfeeding did not lead to poor growth; children's poor growth and health led
      to increased breastfeeding. Children's health must be considered when evaluating
      the association of breastfeeding with anthropometric outcomes.

PMID- 9169171
TI  - High maternal mortality levels and additional risk from poor accessibility in two
      districts of northern province, Zambia.
AB  - BACKGROUND: Maternal mortality ratios in Kasama and Kaputa Districts, two remote
      rural areas of Northern Province, Zambia, were suspected to be very high. In
      order to evaluate the impact of a referral system baseline maternal mortality
      levels and additional maternal mortality risk arising from poor accessibility
      were estimated. METHODS: The sisterhood method was applied to a random population
      sample of 3123 respondents in Kasama District and to 2953 in Kaputa District
      during May and June 1995. For Kasama also hospital-based maternal mortality was
      calculated from record analysis from 1 January 1991 up to 31 December 1995.
      Population attributable risk and population etiological fraction were calculated
      for Kasama District. RESULTS: Maternal mortality ratio for Kasama District was
      764 per 100,000 live births and 1549 for Kaputa District. Kasama hospital-based
      maternal mortality was 543 per 100,000 live births. In Kasama District population
      attributable risk of maternal mortality from poor accessibility was 220 maternal
      deaths per 100,000 live births, and the population etiological fraction was 29%.
      In Kaputa District population attributable risk was 1006 maternal deaths per
      100,000 live births, and the population etiological fraction was 65%.
      CONCLUSIONS: This study suggests that solving the accessibility problem would
      decrease the mortality burden from maternal causes with at least 29% in Kasama
      District and 65% in Kaputa District.

PMID- 9169172
TI  - Gynaecological correlates of hysterectomy in Danish women.
AB  - BACKGROUND: The aim has been to assess the gynaecological characteristics of
      importance for hysterectomy performed for benign diseases. METHODS: In a
      prevalence study, 2301 Danish women aged 30, 40, 50, or 60 years, were selected
      at random in 1982, and self-report questionnaires were collected from 77%.
      Information about gynaecological and obstetric history, social background, weight
      and dieting history, and various lifestyles were recorded. Weight and height were
      measured. In an incidence study, the cohort was followed during 1982-1990 via
      central registers to assess the incidence of hysterectomy. Logistic and Cox
      regression were used to analyse data. RESULTS: In the prevalence study, 85% of
      the hysterectomies were performed for benign conditions. Early menarche (< or =
      11 years old) and short-term use of oral contraceptives (OC) (1-4 years) were
      independent correlates of these hysterectomies by multivariate analyses, whereas
      multiparity (> or = 4 childbirths) was confounded by education and weight-related
      factors. Long-term use of OC was associated with lower prevalence of
      hysterectomy. In the incidence study, short-term use of OC and ever use of
      progestogen-only minipills were independent risk factors for hysterectomy
      performed recently for benign diseases in women under 50 in the multivariate
      analyses. Abortions did not reach significance, and neither multiparity, long
      term use of OC, nor early menarche were important. CONCLUSION: The most important
      gynaecological characteristics related to premenopausal hysterectomy performed
      for benign diseases are hormonal contraceptives. These findings imply that the
      decision-making process concerning hysterectomy might depend on women's choice of
      contraception and compliance with OC as medical treatment.

PMID- 9169173
TI  - Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses
      and canning factories.
AB  - BACKGROUND: Apart from the use of vibrating tools, little is known about risk
      factors for Raynaud's phenomenon. However, it has been hypothesized that this
      disorder may have a multifactorial aetiology, involving potential causal or
      triggering factors which can be found in the workplace. The objective of the
      study is to identify individual and occupational risk factors of Raynaud's
      phenomenon in a population of workers not exposed to vibration, but exposed to
      cold. METHODS: The survey was carried out in 1987-1988 in 17 poultry
      slaughterhouses and six canning factories and included 1474 employees. Data were
      collected at the annual visit to the occupational health physician. Finger
      sensitivity to cold and Raynaud's phenomenon were identified from a list of
      symptoms occurring from exposure to cold. The role of potential risk factors was
      assessed using multiple logistic regression. RESULTS: A high prevalence of
      symptoms of finger sensitivity to cold was observed. Raynaud's phenomenon was
      more common in women than in men, was related to family history of the disease
      but not to smoking or alcohol consumption. After controlling for non-occupational
      factors, the following working conditions appeared as risk factors for Raynaud's
      phenomenon: use of plastic gloves, less than four rest breaks, breaks in an
      unheated place, continual repetition of the same series of operations, exertion
      of the arm or hand and being able to think of something else while working.
      CONCLUSION: The study showed that a number of working conditions were associated
      with an increased risk of Raynaud's phenomenon and finger sensitivity to cold.
      Changes in working conditions might reduce the risk of this disorder in the food
      processing industry.

PMID- 9169174
TI  - Prevalence of sleep apnoea syndrome in the Spanish adult population.
AB  - BACKGROUND: Some data indicate that obstructive sleep apnoea syndrome (OSAS), a
      disorder characterized by recurrent episodes of cessation of respiratory airflow
      during sleep, is highly prevalent in the general population but no such data
      exist in southern Europe. METHODS: In the Zaragoza metropolitan area (northeast
      of Spain) a representative sample of 1360 subjects aged > 18 years and selected
      by quota methods according to age, sex and geographical distribution agreed to
      participate. Trained interviewers visited selected residents to administer a
      sleep questionnaire in the presence of a bedmate or another closely-related
      person who lived in the subject's home; anthropometric data and arterial blood
      pressure were also recorded. All participants were invited to record nocturnal
      home oximetry (NHO). The NHO results were classified as 'abnormal' (or consistent
      with OSAS) in the presence of repetitive, short-duration arterial oxyhaemoglobin
      saturation (SaO2) fluctuations. RESULTS: The diagnosis of OSAS was established in
      subjects with loud (severe) snoring + excessive daytime sleepiness + abnormal
      oximetry In the group of 1222 subjects (597 males, 625 females) who agreed to
      have NHO, 63.7% of men and 36.3% of women snored 'usually' or 'always' (severe
      snorers): daytime sleepiness in active situations occurred in 12.1% and 14.4%
      respectively. The association of severe snoring plus daytime sleepiness plus
      abnormal NHO was found in 18 subjects (13 males, 5 females). CONCLUSIONS: We
      estimated that among Spanish adults, 0.8% of women and 2.2% of men meet the
      minimal criteria to diagnose sleep apnoea syndrome.

PMID- 9169175
TI  - Cognitive impairment in the Amish: a four county survey.
AB  - BACKGROUND: The prevalence of probable dementia was determined in a rural,
      homogeneous community of Amish individuals in the Midwestern USA. The Amish are a
      genetically isolated group with a low level of formal education (< or = 8 years)
      and few exposures to modern life, who live in intergenerational setting and have
      strong social support networks. METHODS: Using community directories, trained
      interviewers administered the Mini Mental State Examination (MMSE) and a medical
      history survey to all Amish over 64 years old in a four county area. Individuals
      with scores < 27 (out of a maximum of 30 points) were given additional
      neuropsychological tests. Results were reviewed by a neuropsychologist and
      subjects were classified with regard to probable cognitive impairment. RESULTS:
      The MMSE scores were inversely related with age and directly with education. The
      Amish have higher MMSE scores than reported for the general US population. The
      overall prevalence of probable cognitive impairment for those over 64 years was
      6.4%. The prevalence increased with age and lower education and was lowest among
      married individuals. CONCLUSIONS: The MMSE scores among the Amish were higher
      than the general population despite their low level of formal education. The
      lower level of cognitive impairment among the Amish could reflect a lack of
      inherited susceptibility to dementing diseases, or environmental factors
      characteristic of their traditional lifestyle. Even among this population with <
      or = 8 years of formal education, education may protect against cognitive
      impairment.

PMID- 9169176
TI  - A simple program to create exact person-time data in cohort analyses.
AB  - BACKGROUND: Before disease rates can be calculated a tabulation of the length of
      follow-up for each person in the cohort has to be made. In complicated analyses
      such tabulations are often stratified by many characteristics, some which show no
      change with time, such as gender or year of birth, and some which do change with
      time, such as age or cumulative exposure. Available computer programs often
      restrict the way these tables can be made, particularly when handling time
      dependent variables. METHODS: This paper presents a simple computer program which
      calculates the length of follow-up for each person in a study. RESULTS: Person
      time data can be tabulated by a large number of variables using this method. This
      program is extremely flexible in the way that time-dependent variables can be
      created, can categorize observations by any unit of person-time, and will run on
      a range of platforms including a personal computer. CONCLUSIONS: This method
      should simplify the task of creating person-time data for analyses of disease
      rates in epidemiological studies.

PMID- 9169177
TI  - Survival of AIDS patients according to type of AIDS-defining event. The AIDS in
      Europe Study Group.
AB  - BACKGROUND: There are known to be wide differences in the prognosis of patients
      with a diagnosis of AIDS. In this study of 6578 patients with AIDS form 17
      European centres, we develop a ranking of AIDS-defining illnesses, and determine
      how well this ranking holds after adjustment for potential confounding variables.
      METHODS: Survival from each AIDS-defining event was calculated and ranked using
      Kaplan-Meier estimation of median survival. Cox proportional hazards models with
      each disease modelled as a time dependant covariate were used to determine the
      risk of death after each diagnosis, before and after adjustment for potential
      confounders. RESULTS: Median survival after an initial AIDS-defining diagnosis of
      progressive multifocal leukoencephalopathy and malignant lymphoma was
      particularly poor (2 and 5 months respectively), while the longest median
      survival occurred after initial AIDS-defining illnesses of Kaposi's sarcoma and
      extrapulmonary tuberculosis (17 and 22 months respectively) Patients diagnosed
      with a primary brain lymphoma had shorter median survival times than patients
      with a peripheral lymphoma (median survival of 1 month and 4 months respectively
      P < 0.0001). In general, median survival in patients with cutaneous Kaposi's
      sarcoma (skin, oral) was between two and four times longer than patients with
      systemic involvement The ranking of diseases was found to be generally similar
      after adjustment for all potential confounders. CONCLUSIONS: AIDS-defining events
      can be grouped into three categories with median survival after diagnosis of < 6
      months. 6-12 months and > 12 months. The assigned ranking of disease would not be
      altered by prognostic factors such as age or CD4 lymphocyte count. These results
      have important implications in the design of clinical trials and patient
      management.

PMID- 9169178
TI  - HIV-related risk factors of blood donors in northern Thailand before and after
      knowing HIV test results.
AB  - BACKGROUND: The epidemic of Human Immunodeficiency Virus (HIV) infection led
      blood banks to initiate donation deferral criteria based on self-reported risk
      factors. However little information is available on the differences in reporting
      risk factors before and after HIV status is known. METHODS: Between April and
      July 1994, blood donors in a provincial hospital in northern. Thailand were
      interviewed at the time of donation, about their demographic characteristics and
      risk factors. All donors had agreed to learn their test results and were called
      back for post-test counselling and reinterview. RESULTS: HIV-positive blood
      donors were more likely to change from 'denying' to 'acknowledging' risk factors
      while HIV-negatives were more likely to change from 'acknowledging' to 'denying'.
      The differences between risk factors obtained before and after test results were
      known resulted in stronger, weaker or even opposite risk measures. CONCLUSION:
      The study results raise questions about the impact of the differences in
      reporting HIV-related risk factors by the donors on how effective donation
      deferral criteria can be developed.

PMID- 9169179
TI  - HIV infection and sexual behaviour among women with infertility in Tanzania: a
      hospital-based study.
AB  - BACKGROUND: Infertility is common in Africa, but virtually no data exist on HIV
      prevalence among infertile women. Mainly anthropological studies in Africa have
      shown that infertile women have higher risks of marital instability and possibly
      also have more sexual partners than fertile women. METHOD: This study was
      conducted in a hospital in northwest Tanzania during 1994 and 1995. Women
      presenting themselves with infertility problems to the outpatient clinic were
      interviewed, examined and blood was drawn. Women who came to deliver in the
      hospital, excluding primiparae, were taken as a control group. The analysis was
      limited to women > or = 24 years. In total 154 infertile and 259 fertile women
      were included in the study. RESULTS: HIV prevalence was markedly higher among
      infertile women than among fertile women: 18.2% and 6.6% respectively (adjusted
      odds ratio [OR] for age, residence and occupation 2.7; 95%-confidence interval
      [CI]: 1.4-5.3). Data on past sexual behaviour showed that infertile women had
      more marital breakdowns, more lifetime sexual partners and a higher level of
      exposure to sexually transmitted diseases (STD). CONCLUSION: Women with fertility
      problems appear to have higher HIV prevalence, which justifies more attention for
      such women in the context of AIDS programmes. In addition, caution is needed when
      using sentinel surveillance data from antenatal clinics to monitor HIV
      prevalence.

PMID- 9169180
TI  - Effect of age, sex and smoking habits on pneumococcal antibodies in an elderly
      population.
AB  - BACKGROUND: Pneumococcal infections are a common cause of morbidity and mortality
      among elderly people. Protection against pneumococcal infections is mediated by
      serotype-specific antibodies to capsular polysaccharides. To obtain an estimate
      of anti-pneumococcal immunity, prevalence and levels of pneumococcal antibodies
      were studied in an unvaccinated elderly population. METHODS: IgG antibodies to
      pneumococcal serotypes 3, 6A, and B and to cell wall polysaccharide (C-PS, a
      common antigen to all pneumococci) were measured by enzyme immuno-assay in 480
      subjects aged 64-97 years (206 men, 274 women) who were a random sample (41%) of
      elderly inhabitants in a semirural community in Finland. RESULTS: An average of
      10% of the elderly lacked antibodies to serotypes 3, 6A, and 8, and 62% of the
      elderly had them in low titres only. Anti-C-PS antibodies were found in 99% of
      the elderly, and in significantly higher titres than anti-capsular antibodies.
      Antibody titres to C-PS and to type 6A decreased with age. Elderly women had
      significantly lower antibody levels than men. Among the men, current smokers had
      higher antibody titres than non-smokers; in the women, this analysis was not
      possible because of infrequent history of smoking. The effect of smoking on
      antibody titres was reversible after cessation of smoking. CONCLUSIONS: A
      considerable proportion of the elderly lacked protective antibodies to commonly
      infecting pneumococcal serotypes 3, 6A, and 8. Smoking increased the prevalence
      and levels of pneumococcal antibodies probably as a consequence of numerous
      respiratory infections. These observations emphasize the importance of
      administration of the pneumococcal vaccine among the elderly.

PMID- 9169181
TI  - Prevention of congenital toxoplasmosis in Szeged, Hungary.
AB  - BACKGROUND: Toxoplasma gondii infection of the fetus can only be discovered or
      prevented by the appropriate serological screening and subsequent treatment of
      the mother and her offspring. In Hungary, there is no obligatory toxoplasma
      screening for pregnant women and both the reporting and follow-up of congenital
      toxoplasmosis cases is limited. In 1987 we started a systematic study in the
      Szeged region of Hungary, in which all pregnant women were screened and
      appropriate treatment given to all mothers and their offspring where congenital
      toxoplasmosis was suspected. METHODS: All pregnant women were routinely screened
      within the first 16 weeks of gestation for toxoplasma antibodies by complement
      fixation test (CFT). Seronegative cases were retested for possible seroconversion
      every second month. Patients with CFT titres > or = 1:256 were retested for anti
      P30 immunoglobulin A (IgA), IgM and IgG antibodies by ELISA and/or SDS-PAGE
      Western immunoblot in order to distinguish the acute and chronic phases of the
      infection. RESULTS: Up to the end of 1994, the sera of 17,735 gravidae were
      screened. Ten women were found to have seroconverted during pregnancy and 78 had
      high initial antibody levels accompanied by anti-P30 IgA antibodies at the very
      first screening. These two groups together were considered as definitely (10) or
      possibly (78) infected with Toxoplasma during pregnancy and were treated with
      Spiramycin. All of their offspring were also treated for one month and followed
      up by systematic serological and clinical screening for 2 years. No congenital
      toxoplasmosis was found in any of the offspring. CONCLUSIONS: Antenatal, early
      diagnosis and treatment of toxoplasmosis in mothers, together with treatment and
      follow-up of their offspring, may considerably reduce the incidence of the
      disease in the offspring.

PMID- 9169182
TI  - Prevalence of trachoma in eastern Turkey.
AB  - BACKGROUND: This study aims to define the prevalence of trachoma in Erzurum, a
      town in Eastern Turkey where all types of conjunctivitis are known to be endemic.
      METHODS: To determine the epidemiological characteristics of the active and
      residual disease in the area, we chose 20% of the households in 17 residential
      areas using simple random sampling. RESULTS: We examined 6386 individuals aged <
      30 and 2220 aged > 30 years. The active and the residual prevalence of the
      disease was found to be 3.2% in those aged < 30, and 1.9% for the group aged > or
      = 30. Risk factors included crowded households with five or more members,
      infrequent washing of the face, visiting thermal springs and the mutual use of
      towels by household members. According to the laboratory findings, trachoma with
      conjunctival smear was found positive in the first and second stages, but
      seropositivity was quite high in the third and fourth stages. The validity of the
      methods used for the diagnosis and the positive predictive values showed the
      sensitivity of the eyelid examinations to be 55.3%, specificity 95.4% and
      positive predictive value 23.9% which were the highest values in the field
      survey. CONCLUSIONS: Trachoma continues to be a serious public health threat in
      Erzurum, and eyelid examination is the most suitable method of diagnosis for
      surveillance of trachoma.

PMID- 9169183
TI  - Protective effect of breastfeeding on invasive Haemophilus influenzae infection:
      a case-control study in Swedish preschool children.
AB  - BACKGROUND: In Orebro County a 2.5-fold increase in the incidence of Haemophilus
      influenzae (HI) meningitis was found between 1970 and 1980, an observation that
      initiated the present study. MATERIALS AND METHODS: In order to search for
      associations between morbidity in invasive HI infection and possible risk
      factors, a case-control study was conducted over a 6-year period from 1987 to
      1992, before general Hib vaccination was introduced in Sweden. Fifty-four cases
      with invasive HI infection 139 matched controls were studied for possible risk
      factors such as day-care outside the home, short duration of breastfeeding,
      passive smoking, low socioeconomic level of the household, many siblings in the
      family, allergy, frequent, infections, repeated antibiotic treatments and
      immunoglobulin deficiency. RESULTS: Multivariate analysis showed a significant
      association between invasive HI infection and two independent factors, i.e. short
      duration (< 13 weeks) of exclusive breastfeeding, odds ratio (OR) 3.79 (95%
      confidence interval [CI] 1.6-8.8) and history of frequent infections, OR 4.49
      (95% CI : 1.0-21.0). For the age at onset 12 months or older, the associations
      were stronger, OR 7.79 (95% CI : 2.4-26.6) and 5.86 (95% CI : 1.1-30.6),
      respectively. When breastfeeding duration in weeks was analysed as a continuous
      variable the OR was 0.95 (95% CI : 0.92-0.99), indicating a decreased risk with
      each additional week. Increased OR were observed for other risk factors as well
      but not of the magnitude found for short duration of breastfeeding. DISCUSSION:
      The association of decreased risk for invasive HI infection and long duration of
      breastfeeding was persisting beyond the period of breastfeeding itself. This
      finding supports the hypothesis of a long-lasting protective effect of
      breastfeeding on the risk for invasive HI infection. CONCLUSION: A decreased risk
      for invasive HI infection with long duration of breastfeeding was found. Our
      results do have implications for strategies in breastfeeding promotion,
      especially in countries where Hib vaccination is too costly and not yet
      implemented.

PMID- 9169184
TI  - The geographical distribution of tick bites and erythema migrans in general
      practice in The Netherlands.
AB  - BACKGROUND: Lyme disease is caused by Borrelia burgdorferi which is transmitted
      in Europe by the tick ixodes ricinus. Erythema migrans is a skin lesion which is
      pathognomonic of Lyme disease. A retrospective study was carried out to determine
      the geographical distribution of the occurrence of tick bites and erythema
      migrans in the Netherlands and to identify ecological risk factors. METHODS: In
      April 1995, all general practitioners (GPs) in the Netherlands were asked to
      complete a postal questionnaire on the number of tick bites and erythema migrans
      case-patients seen in 1994 and the size of the practice. Reminders were sent to
      non-responders. Information on ecological risk factors by local government area
      was obtained from a geographical information system. RESULTS: The response rate
      was 79.9%. In 1994, GPs reported seeing approximately 33,000 patients with tick
      bites and 6500 with erythema migrans. The incidence rate of erythema migrans was
      estimated at 4.3 per 10,000 population. Ecological risk factors for both tick
      bites and erythema migrans were the proportion of the area covered by woods,
      sandy soil, dry uncultivated land, the number of tourist-nights per inhabitant
      and sheep population density. The cattle population density was a risk factor for
      erythema migrans. CONCLUSIONS: Using simple methods, a crude estimate of the
      incidence rate of erythema migrans was obtained rapidly, and high risk areas were
      identified. Lyme disease appears to be an important problem in the Netherlands.

PMID- 9169185
TI  - Is malnutrition associated with prolonged breastfeeding?

PMID- 9169186
TI  - Inguinal hernia repair: incidence of elective and emergency surgery, readmission
      and mortality.

PMID- 9169187
TI  - Validity of ICD code 410 to identify hospital admission for myocardial
      infarction.

PMID- 9169188
TI  - Level curves in Lexis diagrams.

PMID- 9169189
TI  - In vitro reconstitution and analysis of mononucleosomes containing defined DNAs
      and proteins.
AB  - Increasingly, biochemical analyses of processes that occur within eukaryotic
      nuclei such as transcription and replication require the construction of specific
      chromatin substrates. Nucleosome complexes reconstituted in vitro have been key
      elements in a variety of recent studies of polymerase progression and trans
      acting factor binding activities. Reconstituted complexes can be easily
      constructed from purified components in quantities suitable for biochemical and
      biophysical studies. In addition, reconstituted mononucleosome complexes exhibit
      native biochemical and biophysical properties but necessarily contain much less
      heterogeneity with regard to both protein and DNA components than bulk complexes
      isolated from natural sources. This review details the protocols for
      reconstitution of model mononucleosome complexes that contain unique DNA
      sequences and specifically tailored core histone proteins and describes common
      pitfalls associated with these procedures.

PMID- 9169190
TI  - Transcription of dinucleosomal templates.
AB  - Nucleosomes and the chromatin structures they assemble provide the architectural
      foundation for the transcription process. We describe the use of reconstituted
      chromatin templates assembled using purified histones and HMGs to investigate the
      significance of chromatin structure for transcription. Our structural assays
      include sucrose gradient fractionation, nucleoprotein gel analysis, micrococcal
      nuclease digestion, DNase I and hydroxyl radical cleavage mapping of nucleosome
      position, and determination of nucleosome mobility. We determine the consequences
      of incorporation of linker histones or HMG1 on the properties of the nucleosome
      and the transcription process. Our results indicate that linker histones and HMG1
      can direct the positioning of core histone-DNA interactions, restrict nucleosome
      mobility, and repress transcription.

PMID- 9169191
TI  - Nucleoprotein gel electrophoresis for the analysis of nucleosomes and their
      positioning and mobility on DNA.
AB  - Nucleoprotein gel electrophoresis, as well as its use in chromatin research, is
      reviewed from its early application in the characterization of native nucleosome
      composition to current uses in analyzing transcription factor-nucleosome
      complexes and in visualizing multiple nucleosome positioning. Despite our
      incomplete understanding of the principles behind the separation of particles in
      native polyacrylamide, gels, powerful new applications of the method have emerged
      in recent years. This offers the potential for novel experimental strategies,
      such as those that have led to the discovery of nucleosome mobility.

PMID- 9169192
TI  - Biochemical analysis of chromatin structure and function using Drosophila embryo
      extracts.
AB  - The biochemical analysis of chromatin structure and function is greatly
      facilitated by the availability of cell-free systems that assemble chromatin
      under physiological conditions. One such system that has shown great potential is
      derived from extracts of early Drosophila embryos. These embryos contain large
      maternal stocks of chromatin constituents, such as histones and assembly factors.
      Chromatin assembled in these extracts resembles native chromatin in many
      respects: it displays physiological nucleosome repeat lengths, it is complex,
      containing a wealth of nonhistone proteins as well as enzymatic activities, and
      it has dynamic properties that allow the interaction of DNA-binding proteins that
      regulate important cellular processes. Most importantly, chromatin with variant
      properties, e.g., with respect to the basic geometry of the nucleosomal array,
      histone modifications, and its content of linker histones or nonhistone proteins,
      can be obtained by manipulating the reconstitution conditions. The synthesis of
      uniform chromatin with specific characteristics should allow the analysis of the
      functional significance of the structural and biochemical heterogeneity observed
      in vivo.

PMID- 9169193
TI  - Chromatin studies by DNA-protein cross-linking.
AB  - Our current level of understanding of chromatin structure was to a large extent
      achieved with the help of DNA-protein cross-linking. The versatile inventory of
      cross-linking techniques allows the identification of the contacts between DNA
      and proteins with a single nucleotide-single amino acid precision, to detect
      minor components of the complex nucleoprotein systems, to reveal the interactions
      of the flexible protein domains with DNA, and to assay for conformational changes
      in the nucleosomes.

PMID- 9169194
TI  - Chromosomal mapping of core histone acetylation by immunoselection.
AB  - Acetylation of specific lysine residues in the N-terminal domains of core
      histones is a biochemical marker of active genes. To determine the spatial and
      temporal distribution of this reversible posttranslational modification, affinity
      purified polyclonal antibodies recognizing the epitope epsilon-acetyllysine have
      been used in immunoselection procedures with mononucleosomes and salt-soluble
      chromatin fragments generated by micrococcal nuclease. The DNA of the antibody
      selected chromatin was slot-blotted and probed with a variety of gene sequences:
      an enhanced hybridization signal, with respect to that from the DNA of the input
      chromatin, demonstrated elevated acetylation levels on the histones associated
      with the probing sequences. Using chicken embryonic erythrocytes as chromatin
      source and probes from the beta globin locus, it was shown that both the
      embryonic epsilon and adult beta genes are acetylated at 5 and 15 days, and the
      acetylation uniformly covers the whole of the locus, precisely comapping with the
      33 kb of open chromatin structure. Studies with proliferating human K562 cells
      show that the inactive but poised PDGF-beta gene is already hyperacetylated and
      that its acetylation status is not enhanced on induction. These results indicate
      that acetylation is not a consequence of transcription but a prerequisite and
      that it may be responsible for either generating or maintaining the open
      structure of poised and active genes.

PMID- 9169195
TI  - Fine resolution of histones by two-dimensional polyacrylamide gel
      electrophoresis: developmental implications.
AB  - A two-dimensional electrophoresis for fine separation of histones is described in
      detail. The method is relatively simple and gives very reproducible results. In
      the first dimension the histones are separated by their charge in acid-urea gels,
      while in the second dimension the separation is based on both the charge and the
      differential affinity of histones to Triton in acid-urea-Triton gels. In this
      electrophoretic system, the linker histones are resolved on the gel diagonal,
      while the core histones are separated above the diagonal. The electrophoresis is
      very sensitive to charge effect, and thus it is very well suited to resolving
      histone-modified forms. The application of the two-dimensional electrophoresis in
      Xenopus developmental studies is illustrated.

PMID- 9169196
TI  - Analytical ultracentrifugation and agarose gel electrophoresis as tools for
      studying chromatin folding in solution.
AB  - Analytical ultracentrifugation and agarose gel electrophoresis each can be used
      to accurately quantify changes in structure that accompany chromatin folding in
      solution. Analytical ultracentrifugation directly measures the extent of
      compaction of each species present in a chromatin sample under a wide range of
      solution conditions. Agarose gel electrophoresis yields information about changes
      in the average surface charge density, size and/or shape, and conformational
      flexibility during chromatin folding. When used together, these methodologies are
      particularly powerful. Protocols for the characterization of chromatin folding by
      analytical ultracentrifugation and agarose gel electrophoresis are described.
      Discussion focuses on analysis and interpretation of experimental chromatin
      folding data.

PMID- 9169197
TI  - Visualization and analysis of chromatin by scanning force microscopy.
AB  - The use of the scanning force microscope (SFM) to visualize and analyze chromatin
      fiber structures is presented. Protocols to prepare chromatin fibers for SFM
      imaging of fibers in air and in buffer are first discussed. Next, the conditions
      for acquiring high-quality SFM images such as optimal instrumental parameters,
      appropriate deposition substrates, and adequate procedures of sample deposition
      are described. It is shown that analysis and quantitation of the SFM images
      support an irregular, three-dimensional arrangement of nucleosomes in the native
      chromatin fiber. This structure is lost in linker histone-depleted fibers, which
      show, instead, a beads-on-a-string structure. Molecular modeling of the chromatin
      fiber structures and computer simulation of the SFM imaging process indicate that
      the natural variability of the linker length may be the major determinant of the
      structural irregularity of the native chromatin fiber. Removal of linker histones
      (H1/H5) may change the amount of DNA wrapped around the histone octamer, which in
      turn may induce the transition from a three-dimensional irregular helix to an
      extended beads-on-a-string structure. Studies of trinucleosomes indicate that
      both the average successive nucleosome center-to-center distance and the average
      angle between two successive linkers increase upon the removal of linker histone.

PMID- 9169198
TI  - Electron microscopy of chromatin.
AB  - Electron microscopy, with its ability to image DNA and nucleosomes, can provide a
      key visual link in the understanding of chromatin conformation. We discuss
      applications of EM to current chromatin research with emphasis on strategies that
      eliminate many of the potential problems associated with conventional EM
      preparative techniques. Cryo-electron microscopy (cryo-EM) of isolated chromatin,
      whereby samples are imaged "in solution" in thin vitrified films, is considered
      in detail, with emphasis on the recovery of three-dimensional information and on
      its application to linker DNA conformation and to salt-induced compaction.
      Factors that currently limit the technique, and the prospects of overcoming them,
      are also considered.

PMID- 9169199
TI  - Assays for transcription factors access to nucleosomal DNA.
AB  - Several promoters have been shown to have sequence specifically positioned
      nucleosomes that determine the architecture of the promoter. DNA binding proteins
      that regulate gene expression are in many cases known to bind to their cognate
      DNA segments organized within such positioned nucleosomes. It has become
      increasingly evident that the cooperation of chromatin and transcription factors
      results in an efficient and fine-tuned regulation of transcription. The first
      step in a gene induction event must be the access of transcription factors for
      the regulatory promoter/enhancer target sites. In this perspective it becomes
      interesting to evaluate the affinity of DNA binding proteins for their cognate
      binding site in a nucleosome context. Here we describe the preparation of
      nucleosome probe, a method for in vitro nucleosome reconstitution by salt
      dilution, purification of the reconstituted mononucleosomes, and characterization
      of the translational and rotational positions of the nucleosomal DNA. In
      addition, methods for affinity determination and characterization of protein
      nucleosomal DNA interaction, such as methylation protection and methylation
      interference by dimethyl sulfate, quantitative DNase I footprinting, and
      electrophoretic mobility shift assay, are described.

PMID- 9169200
TI  - Analysis of chromatin structure in vivo.
AB  - A number of important nuclear processes including replication, recombination,
      repair, and transcription involve the interaction of soluble nuclear proteins
      with DNA assembled as chromatin. Recent progress in a number of experimental
      systems has focused attention on the influence chromatin structure may exert on
      gene regulation in eukaryotes. With the advent of new technologies for the
      analysis of chromatin structure in vivo, studies evaluating the influence of
      chromatin structure on gene transcription have become feasible for a number of
      systems. This article serves as an introduction to the use of restriction
      endonucleases to define nucleosomal organization and characterize changes in this
      organization that accompany transcriptional activation in vivo. The procedure
      includes the isolation of intact transcriptionally competent nuclei, limited
      digestion with specific restriction endonucleases, and purification of the DNA.
      This DNA serves as the substrate for a linear amplification using single primers
      that generate enzyme-specific DNA fragments, which are then resolved by
      electrophoresis. Specific examples related to our studies of the influence of
      chromatin structure on steroid hormone regulation of transcription from the mouse
      mammary tumor virus promoter are provided to illustrate this technique and
      several novel variations. Alternative methods for analysis of chromatin
      architecture using DNase I, micrococcal nuclease, permanganate, and
      methidiumpropyl-EDTA-iron(II) are also described. Through the use of these
      methodologies one is able to determine both the translational and the rotational
      positions for a given nucleosome as well as quantify changes at a specific
      nucleosome in response to regulatory and developmental signals.

PMID- 9169201
TI  - Sequence analysis of plasmid pCC5.2 from cyanobacterium Synechocystis PCC 6803
      that replicates by a rolling circle mechanism.
AB  - The cyanobacterium Synechocystis sp. strain PCC 6803 contains several cryptic
      plasmids of 2.4, 5.2, and about 50 or 100 kbp. The complete nucleotide sequence
      of the 5.2-kbp plasmid, pCC5.2, has been analyzed and is reported here. This
      plasmid contains 5214 bp and 53.1% A+T. Six open reading frames, ORFs A-F
      (encoding peptides of larger than 90 amino acid residues), were located on both
      strands of pCC5.2. ORF B codes for a potential replication protein containing 971
      amino acids, for which there are three homologous proteins encoded by other
      cyanobacterial plasmids. ORF C encodes a polypeptide of 93 amino acids which
      shares homologies with products of two ORFs found in the protein database.
      Counterparts of the products of ORF A, D, E, and F could not be found in the
      protein database. Detection of a single-stranded DNA intermediate during
      replication of pCC5.2 indicates that this plasmid may also replicate by a rolling
      circle mechanism, as has been reported for pCA2.4 and pCB2.4 from the same strain
      of Synechocystis (PCC 6803).

PMID- 9169202
TI  - The resistance and integrase genes of pACM1, a conjugative multiple-resistance
      plasmid, from Klebsiella oxytoca.
AB  - pACM1 is an 85-kb conjugative plasmid from a clinical isolate of Klebsiella
      oxytoca that encodes resistance to beta-lactams (mediated by SHV-5 extended
      spectrum beta-lactamase), trimethoprim, sulfonamides, tetracycline,
      aminoglycosides, and mercuric chloride. The expression of the aminoglycoside
      resistance is difficult to detect, which could have clinical implications. A
      region of pACM1 containing five resistance genes and two putative integrons was
      characterized by restriction mapping and partial DNA sequencing. One integron
      appears to be class I (sull type); the second lacks a recognizable 3' conserved
      segment. Neither integron has the BamHI site predicted for the 5' conserved
      segment. Plasmids encoding SHV-5 from other bacterial strains appear to be
      closely related to pACM1 by restriction enzyme analysis, but have resistance/
      integron regions that vary in size and content from that of pACM1. Integrase
      mediated recombination might be responsible for genetic divergence in a widely
      distributed family of pACM1-like plasmids.

PMID- 9169203
TI  - Molecular properties of the erythromycin resistance plasmid pPV141 from
      Staphylococcus chromogenes.
AB  - The 2.3-kb erythromycin resistance (EmR) plasmid pPV141 of Staphylococcus
      chromogenes 3688 was isolated and characterized. Nucleotide sequence analysis
      identified ORF1 and ORF2 separated by a 445-bp spacing, encoding a 158-residue
      replication protein (Rep141) and a 244-residue erythromycin resistance protein
      (Erm, rRNA adenine N-6-methyltransferase), respectively. Structural analysis and
      Southern hybridization showed that the rep and ermM genes in pPV141 shared
      homology with other known EmR plasmids. Based on sequence analysis, pPV141 was
      classified as a unique member of the pSN2 family of EmR plasmids.

PMID- 9169204
TI  - Unmarked gene integration into the chromosome of Mycobacterium smegmatis via
      precise replacement of the pyrF gene.
AB  - After integration into the bacterial chromosome an exogenous gene may be stably
      expressed without continued selection for the recombinant locus. However,
      chromosomal integration events occur infrequently, requiring the concomitant
      integration of a drug resistance marker in order to identify colonies of
      recombinant cells. The generation of a drug-resistant recombinant strain can both
      reduce the in vivo applicability of the strain and preclude the use of
      recombinant vectors which use the same drug resistance marker. We have
      constructed a plasmid, pINT-delta, which allows recombination of exogenous genes
      onto the Mycobacterium smegmatis chromosome. The exogenous gene completely
      replaces the pyrF gene and the resultant strain lacks any exogenous drug
      resistance marker. The methodologies described herein are general and applicable
      even to those bacteria for which extrachromosomal plasmids are not available.
      Using pINT-delta we integrated the lacZ gene into the M. smegmatis chromosome via
      a precise exchange of lacZ and pyrF. The resultant strain was used to demonstrate
      that the expression of genes integrated at the pyrF locus is repressed twofold by
      inclusion of uracil in the growth medium. In addition, we used pINT-delta to
      construct an M. smegmatis strain with a precise deletion of its pyrF locus. This
      strain, TSm-627, grows normally in rich medium but does not grow in medium
      lacking uracil. TSm-627 cells allow the pyrF gene to be used as a selectable
      marker for growth on medium lacking uracil. In TSm-627 cells, the pyrF gene is
      also useful as a counterselectable marker on complete medium containing 5'
      fluoroorotic acid and uracil. Two pyrF-containing plasmids, designed to exploit
      the new delta pyrF strain, have been constructed and their possible applications
      to problems in mycobacteriology are discussed.

PMID- 9169205
TI  - Transfection of Actinomyces spp. by genomic DNA of bacteriophages from human
      dental plaque.
AB  - Bacteriophages that produced turbid or clear zones of lysis in strains of
      Actinomyces were isolated from 22 of 124 samples of fresh human dental plaque.
      All human and nonhuman strains of Actinomyces viscosus or Actinomyces naeslundii
      tested in this study were sensitive to infection by one or more of these phages.
      In contrast, none of the Actinomyces odontolyticus, Actinomyces israelii, or
      Actinomyces bovis strains tested were susceptible. Results of restriction
      endonuclease analyses indicated that the genomes of these phages consisted of
      double-stranded DNA molecules ranging in size between 16 and 60 kbp. Sequence
      homology under hybridization conditions of high stringency was observed among a
      few of the isolated phages. A lysogenized isolate of A. viscosus MG-1 was
      obtained following infection with a temperate phage, designated phi 225. Results
      of Southern blot analyses indicated that phi 225 replicated as a plasmid in the
      lysogenized strain. Genomic DNA from several lytic phages was used to establish
      conditions for transfection by electroporation of strains of Actinomyces spp.
      Efficiencies of DNA transfer ranged from 10(2) to 10(5) plaque-forming units per
      microgram of DNA were obtained under optimal transfection conditions. The results
      of these studies demonstrate that transfer of genetic information in Actinomyces
      spp. can be achieved by transfection.

PMID- 9169206
TI  - An expression vector encoding a lacZ reporter gene facilitates identification of
      stable, high-producing CHO cell clones.
AB  - We describe a vector and a streamlined procedure for isolating high-producing
      stable mammalian cell transfectants. The vector encodes the Escherichia coli lacZ
      gene as a reporter. We show that levels of beta-galactosidase activity, assayed
      in situ in clonal isolates, can be used to identify clones producing high levels
      of the protein of interest (in this case, soluble human CD4 protein).

PMID- 9169207
TI  - The distribution of visual attention in infants.
AB  - In this study, the relationships between the length, number, and distribution of
      looks were investigated. To this end, 5-, 7-, and 9-month-old infants were
      familiarized for 24 or 36 s with two identical geometric forms and tested with a
      novel form paired with the familiar one. The distribution of individual looks to
      different portions of the display were monitored. At all ages, infants who had
      briefer looks (short lookers) demonstrated more broadly distributed looks than
      long lookers; they showed more looks, more shifts, and inspection of more
      stimulus areas. Also, the greater numbers of shifts exhibited by short lookers
      included more horizontal, vertical, and diagonal shifts than long lookers. During
      the test trials, short lookers, primarily in the 5- and 9-month sample,
      demonstrated greater novelty preference. Data from this study suggest that the
      distribution of attention is related to short and long looking as is found when
      visual attention is assessed at a micro level (e.g., Bronson, 1991).

PMID- 9169208
TI  - Employing computer technology to assess visual attention in young children and
      adolescents with severe mental retardation.
AB  - The intent of this investigation was to establish a valid and sensitive computer
      measurement technique for educational assessment applications. An integral part
      of the investigation was to establish the similarities and differences in how
      prior reinforcement histories of individual stimuli affect attention to compound
      visual cues for young children of normal development versus adolescents with
      severe mental retardation, both groups having comparable mental age. A series of
      identical conflict compound discrimination tasks was presented to the two groups.
      In addition, generalization effects were investigated for both groups by
      presenting compounds containing some or all novel cues. The similarities and
      differences in performance for young children of normal development and
      adolescents with severe mental retardation were analyzed using multiple testing
      procedures. In addition to assessing stimulus control by presenting stimulus
      components separately following acquisition of compound discriminations, response
      topographies of the compound stimuli were recorded with a touch screen attached
      to a computer monitor screen. This study demonstrated that overselective
      attention did not occur only for students with severe mental retardation but also
      for young children of normal development if multiple tests were employed. A
      difference was found, however, between the two populations in the efficiency with
      which they shifted attention among elements of complex stimuli depending on prior
      conditioning histories. Presentation of compounds whose components had
      conflicting reinforcement histories was found to be a more sensitive assessment
      technique than presentation of compounds containing some or all novel components
      for distinguishing between the two groups. The use of multiple testing procedures
      was critical in preventing false conclusions from altered test performances
      arising from reinforcement contingencies in effect during the test.

PMID- 9169209
TI  - Picture naming by young children: norms for name agreement, familiarity, and
      visual complexity.
AB  - Researchers concerned with the development of cognitive functions are in need of
      standardized material that can be used with both adults and children. The present
      article provides normative measures for 400 line drawings viewed by 5- and 6-year
      old children. The three variables obtained-name agreement, familiarity, and
      visual complexity-are important because of their potential effect on memory and
      other cognitive processes. The normative data collected in the present study
      indicate that young children are different from adults in both the name most
      frequently assigned and the number of alternative names provided. The alternative
      names given by the children are either coordinate names or names of objects that
      are visually similar to the pictured object. In addition, the failure (to name)
      rate is higher among young children compared to adults. Thus, we conclude that
      unequivocal interpretation of age-related differences in cognitive functions can
      be made only when age-appropriate pictorial stimuli are chosen.

PMID- 9169210
TI  - Continuous monitoring of intracellular volumes in isolated rat hearts during
      normothermic perfusion and ischemia.
AB  - The present study describes an experimental setup that enables continuous
      measurement of cellular volumes in isolated organs. The procedure is a
      modification of a recently reported method that uses multinuclear NMR measured by
      59Co NMR of cobalticyanide and 1H NMR of water in isolated rat hearts at
      normothermia. The new apparatus contains a background flow which is shown to
      improve the rate of exchange of the marker between the interstitium and the
      external solution and allows detection of cellular shrinkage during no-flow
      ischemia. A series of experiments of marker loading and wash-out were performed
      to validate the method. In the Langendorff preparation, intracellular volumes (in
      units of milliliters per gram dry weight) of hearts perfused with Krebs-Henseleit
      solution oscillated around a mean value of 2.50 +/- 0.06 ml/gdw. During 30 min of
      ischemia the cells swelled to 2.88 +/- 0.08 ml/gdw and residual edema was
      observed after 30 min of reperfusion (2.62 +/- 0.08 ml/gdw). A hypoosmotic shock
      was used to assess changes in membrane permeability at different time points of
      ischemia and reperfusion. Water influx induced by the hypoosmotic shock at the
      end of ischemia was similar to that elicited in perfused hearts. After 15 and 30
      min of reperfusion, the magnitude of the response to hypoosmolarity decreased by
      9 and 37%, respectively, indicating a gradual permeabilization of the membranes,
      presumably to ions. The experimental setup was also used to monitor intracellular
      volumes as a function of time in anisoosmotic conditions. Cellular
      swelling/shrinkage were delayed for periods of 5 and 8 min at osmolarities of +/
      50 and +/-100 mosmol/liter, suggesting a limited capability of the heart to
      absorb an anisoosmotic shock. The variation in cellular volumes was proportional
      to the deviation of the conditions from isoosmolarity, and activation of volume
      regulatory mechanisms was demonstrated. The noninvasive technique presented in
      this study is capable of providing quantitative evidence of changes in cellular
      volumes in isolated hearts at a temporal resolution of 1 min and a spatial
      resolution of 4% (of cellular volume). As demonstrated in the cases of global
      ischemia and anisoosmolar conditions, the technique is expected to provide new
      insights into the mechanism of cellular-volume regulation.

PMID- 9169211
TI  - Adiabatic slice-selective excitation for surface coils.
AB  - A novel RF pulse designed to perform a diabatic slice-selective excitation for
      surface coils (ASSESS) is proposed in which Bzero gradient is modulated in
      concert with RF frequency modulation. Within the selected slice, the principles
      of BIR4 pulses are employed to obtain well-defined, pure-phase and self-refocused
      spin rotation of arbitrary flip angles despite the presence of high B1
      inhomogeneity produced by surface coils. Outside the slice, advantage is taken of
      the B1 field to dephase equilibrium magnetization to achieve slice selection or
      outer-volume suppression. This scheme should be useful for many localization
      techniques. Quaternion analysis of the overall propagator of the proposed pulse
      and numerical simulations using Bloch equations are performed. The pulse is
      tested experimentally on a phantom sample.

PMID- 9169212
TI  - Double-stacked dielectric resonator for sensitive EPR measurements.
AB  - A new approximate method for predicting the resonant frequencies and for solving
      the field distribution problem of a cylindrical dielectric resonator (DR) is
      developed. The model proposed in this paper bridges the gap between rigorous and
      accurate finite-element or Green function-based numerical methods on the one hand
      and on the other hand, simple approximate solutions in which the field
      distribution can be described analytically, but the resulting frequency is
      accurate within a few percent only. In the method described here, the approximate
      solution for the microwave field distribution is modified by substituting
      different values of the radial separation constants inside and outside of the
      diskshaped DR. The model is generalized for the double-stacked DR structure and
      enables one to introduce corrections that take into account the presence of the
      shielding walls and of the cylindrical sample hole. Good agreement is found
      between experimental and calculated results for both the single and double
      stacked structures that are designed around commercially available X-band DRs (9
      10 GHz). For the resonant frequency of the lowest transverse-electric TEzero1
      delta mode that is commonly used for EPR measurements, the accuracy of the method
      is better than 1%. Experimentally measured resonator filling factors are also in
      good agreement with those theoretically estimated. Both the theory and the
      experimental results suggest that the double-stacked DR structure with finite
      spacing between the ceramic cylinders is the most suitable for EPR measurements
      of long lossy samples.

PMID- 9169213
TI  - Relax, a flexible program for the back calculation of NOESY spectra based on
      complete-relaxation-matrix formalism.
AB  - RELAX is a flexible program for the quantitative analysis of NOESY spectra. It
      allows the simultaneous application of different models describing the internal
      and overall motion of the molecule under investigation for individual spin pairs
      or groups of spins. A correction for anisotropy effects due to the deviation of
      the molecule from a spherical shape is calculated automatically from the trial
      structure. The program can deal with completely relaxed spectra as well as
      spectra recorded with a short relaxation delay. An execution-time-controlled
      splitting of the relaxation matrix reduces the computation time significantly
      without any loss of accuracy. This is especially important for large molecules or
      medium distance cutoffs.

PMID- 9169214
TI  - Calculation of coherence-transfer behavior under planar versus isotropic mixing
      Hamiltonians and application to heteronuclear J cross-polarization experiments in
      solution-state NMR spectroscopy.

PMID- 9169215
TI  - Identification of ribose-base sequential NOEs according to base types in
      uniformly 13C-labeled RNAs.

PMID- 9169216
TI  - Indirect spin-spin coupling in multiple-quantum magic-angle-spinning NMR spectra
      of quadrupolar nuclei.

PMID- 9169217
TI  - Broadband adiabatic refocusing without phase distortion.

PMID- 9169218
TI  - The spatial dependence of spin-echo signals.
AB  - The signals in NMR spin echoes which are refocused by 90 degrees pulses are
      spatially modulated. The spatial modulation is not normally observed in images or
      profiles obtained using Hahn or stimulated echoes, but may cause errors if the
      sample structure varies on the distance scale of the modulation. Localized
      spectra measured using stimulated echoes will also show errors under these
      conditions. Simple Fourier-transform arguments show that conditions which allow
      the modulation to become visible in an image or profile have the effect of
      introducing a second echo into the time-domain acquisition window. Phase cycling
      may be used to remove the spatial dependence of the signals.

PMID- 9169219
TI  - A comparison between different imaging strategies for diffusion measurements with
      the centric phase-encoded turboFLASH sequence.
AB  - The study compared the results of three centrally reordered phase-encoded
      turboFLASH sequences for diffusion-weighted imaging (DWI). The sequences were
      conventional turboFLASH, turboFLASH with subtraction of T1-related effects, and
      turboFLASH with correction for T1-related effects during the imaging period only.
      The relative merits were studied with respect to image quality and accuracy by
      computer simulation and by experimental validation on phantoms and on in vivo rat
      brain. A T1-related underestimation of the diffusion coefficient ranging from 
      30% (T1 approximately 200 ms) to -5% (T1 approximately 1 s) was found to exist
      for the conventional sequence. Image artifacts, caused by longitudinal relaxation
      during the imaging period, are reflected in calculated diffusion maps. When the
      correction sequence is used, the artifacts and the systematic errors are reduced
      but longitudinal relaxation during the delay between preparation and imaging
      periods remains large enough to induce significant errors (-15% for T1
      approximately 200 ms to -3% for T1 approximately 1 s). The subtraction sequence
      eliminates the influence of T1 effects on the calibrations, but leads to
      identical artifacts for all diffusion-weighted images.

PMID- 9169220
TI  - Spinning sidebands in slow-magic-angle-spinning NMR spectra arising from tightly
      J-coupled spin pairs.
AB  - Complex spinning sidebands are observed in magic-angle-spinning (MAS) NMR spectra
      arising from isolated tightly J-coupled spin pairs under slow spinning
      conditions. Such spinning sidebands are sensitive to the magnitude and relative
      orientation of the chemical-shift tensors, the dipolar-coupling tensor, and the
      sign of the indirect spin-spin (J) coupling. We show that it is possible to
      extract information concerning such NMR parameters from an analysis of the
      observed spinning sidebands. As an example, numerical simulations are carried out
      to reproduce observed 31P MAS NMR spectra of a phosphole tetramer (1) and o
      bis(diphenylphosphino)benzene (2), so that invaluable information concerning the
      orientations of the phosphorus chemical-shift tensors and the sign of J(31P, 31P)
      can be deduced. Simulations are carried out by numerically evaluating the spin
      density matrix of the spin system.

PMID- 9169221
TI  - A robust method for estimating cross-relaxation rates from simultaneous fits to
      build-up and decay curves.
AB  - This paper introduces a novel computational method for estimating relaxation
      rates among pairs of spin orders. This method simultaneously estimates all the
      auto- and cross-relaxation rates from the same measurements, and avoids the ill
      conditioning problems associated with multiexponential fits. The method models
      the relaxation dynamics by a system of linear differential equations, and assumes
      that measurements of the spin orders have been made at an equally spaced sequence
      of time points. It computes a nonlinear least-squares fit of the exponential of
      the rate matrix at the shortest time point to these measurements. Preliminary
      estimates of the exponential matrix and initial spin orders from which to start
      the computations are obtained by solving simpler linear-least-squares problems.
      The performance of the method on simulated 2 x 2 test problems indicates that
      when measurements at eight or more equally spaced times spanning the maximum and
      inflection points of the build-up curves are available, the relative errors in
      the rates are usually less than the relative errors in the measurements. The
      method is further demonstrated by applying it to the problem of determining the
      cross correlation-induced cross-relaxation rates between the in-phase and
      antiphase coherence of the amide groups in the 15N-labeled protein oxidized
      flavodoxin. Finally, the possibility of extending the method to other kinds of
      relaxation measurements and larger spin systems is discussed.

PMID- 9169222
TI  - 1H NMR measurements of wet/dry ratio and T1, T2 distributions in lung.
AB  - Proton-magnetic-resonance measurements have been carried out on juvenile porcine
      peripheral lung parenchyma. The free-induction-decay signal contained a
      motionally restricted component which decayed in a few tens of microseconds and a
      mobile component with a T2 time greater than 1 ms. The average second moment, M2,
      for the motionally restricted signal was found to be 3.42 +/- (0.25) x 10(9) s-2.
      The T2 distribution for the mobile signal consistently showed four resolvable
      components of T2 range: 2-6, 10-40, 80-110, and 190-400 ms. The 2-6 ms component
      was present in a fully dehydrated preparation and was therefore assigned to a
      nonaqueous lung constituent. The motionally restricted FID component had a T1 =
      0.772 +/- 0.11 s and the mobile component had a T1 = 0.967 +/- 0.02 s. The
      hydrogen content per unit mass for lung parenchyma and water were estimated in
      two ways: (1) on the basis of chemical content and (2) on the basis of comparison
      of restricted and mobile signals to the gravimetric (G) water content for a lung
      sample studied at a wide range of water contents. Lung wet/dry weight ratios were
      estimated from the free-induction decays and compared with gravimetric
      measurement. The ratio of (wet/dry)NMR/(wet/dry)G was 1.00 +/- 0.08 and 1.00 +/-
      0.05 for the two methods of estimation.

PMID- 9169223
TI  - Four-dimensional 1H and 23Na imaging using continuously oscillating gradients.
AB  - A class of fast magnetic spectroscopic imaging methods using continuously
      oscillating gradients for four-dimensional (three spatial and one spectral)
      localization is introduced. Sampling may start immediately following the
      application of an RF excitation pulse, thus enabling measurement of spin density,
      chemical shift, and relaxation rates of short-T2 species. For spatial
      localization, steady-state sinusoidal gradient waveforms are used to sample a
      ball in k space. The two types of trajectories presented include: (1)
      continuously oscillating gradients with continuously rotating direction used for
      steady-state free-precession imaging and (2) continuously oscillating gradients
      followed by a spoiler directed along discrete projections. Design criteria are
      given and spatial-spectral and spatial-temporal reconstruction methods are
      developed. Theoretical point-spread functions and signal-to-noise ratios are
      derived while considering T2*, off-resonance effects, and RF excitation options.
      Experimental phantom, in vivo, and in vitro 1H and 23Na images collected at 2.35
      T are presented. The 1H images were acquired with isotropic spatial resolution
      ranging from 0.03 to 0.27 cm3 and gradient-oscillation frequencies ranging from
      600 to 700 Hz, thus allowing for the separation of water and lipid signals within
      a voxel. The 23Na images, acquired with 500 and 800 Hz gradient waveforms and
      0.70 cm3 isotropic resolution, were resolved in the time domain, yielding
      spatially localized FIDs.

PMID- 9169224
TI  - Absorption lineshapes in two-dimensional electron spin resonance and the effects
      of slow motions in complex fluids.
AB  - A methodology for obtaining pure absorption two-dimensional electron spin
      resonance spectra is presented for the case of large inhomogeneous broadening
      and/or slow motions. For slow motions, the spectra consist of "complex
      Lorentzians" superimposed with complex weighting factors, presenting a challenge
      to obtaining absorption spectra. It is shown how absorption-type spectra can be
      recovered for the two-pulse COSY and SECSY experiments in such cases. For three
      pulse 2D ELDOR experiments, absorption lineshapes can be obtained for the
      autopeaks, whereas the cross peaks would be of mixed-mode character, in general.
      However, for practical cases the dispersive components in the cross peaks will be
      relatively small. Theoretical and experimental absorption spectra are provided to
      illustrate the method and to show the improved resolution obtained from
      absorption lineshapes. In particular, the variation in linewidths across a SECSY
      spectrum, which is a key component in elucidating motional dynamics, is clearly
      rendered in the pure absorption mode. A convenient method for introducing the
      necessary phase corrections for the slow-motional spectra is also provided.

PMID- 9169225
TI  - Measurement of 1H T1 rho in a uniformly 15N-labeled protein in solution with
      heteronuclear two-dimensional spectroscopy.

PMID- 9169226
TI  - Measurement of dipolar contributions to 1JCH splittings from magnetic-field
      dependence of J modulation in two-dimensional NMR spectra.

PMID- 9169227
TI  - Three-dimensional structure of the porcine gastric H,K-ATPase from negatively
      stained crystals.
AB  - A low-resolution three-dimensional model of membrane-bound H,K-ATPase from pig
      gastric mucosa has been reconstructed by electron microscopy and image processing
      of two-dimensional crystals in negative stain. The crystal formation is induced
      by magnesium and vanadate, which stabilize the E2 conformation of the enzyme. The
      unit cell, with a size of a = b = 123 A, gamma = 90 degrees, has tetragonal p4
      symmetry. There are four separate alpha beta protomers within each unit cell. The
      high-contrast region is limited to the cytoplasmic part of the protein. The total
      volume of the observed asymmetric protein domain corresponds to a molecular mass
      of 80-90 kDa. It consists mainly of a large pear-shaped domain measuring 60 x 45
      A2, with a height of 50 A as measured perpendicular to the membrane plane. A
      small stalk segment, 20 A in length, forms a connection to the transmembrane
      region.

PMID- 9169228
TI  - Staphylococcus aureus alpha-toxin: characterization of protein/lipid
      interactions, 2D crystallization on lipid monolayers, and 3D structure.
AB  - Staphylococcus aureus alpha-toxin was characterized with respect to surface
      activity and its interaction with lipid monolayers. The protein alone had a
      detergent-like behavior at the air/water interface. Its affinity was higher for
      negatively charged than for neutral phospholipids. The interaction was pH
      dependent, showing a maximum increase at pH 7.0. Only a small part of the protein
      oligomer appeared to be inserted into the monolayers. Crystalline sheets of alpha
      toxin were formed using negatively charged phospholipids. Electron microscopy of
      such areas, at different tilt angles, allowed reconstruction of a three
      dimensional model following image processing. The sheets analyzed consisted of
      two protein layers arranged on a tetragonal lattice. Under the conditions used to
      grow the crystals the toxin formed 90-A-wide cylinders with a height of 70 A. One
      of the imposed fourfold axes running perpendicular to the plane of the
      crystalline layer is positioned at a protein-deficient region which forms a 25-A
      wide pore through the oligomer.

PMID- 9169229
TI  - Folding and assembly of hepatitis B virus core protein: a new model proposal.
AB  - Hepatitis B core antigen has been intensively studied. Recently, cryoelectron
      microscopy studies have determined the structure of human and duck hepatitis B
      virus nucleocapsids at low resolution. Both viruses assemble into core particles
      of two sizes with icosahedral dimer-clustered T = 3 and T = 4 symmetries. Both
      capsids present tightly clustered dimers composed of a shell and a protruding
      domain. The present work introduces a model for HBc folding, dimer formation, and
      assembly. The model is based in multiple alignments of HBc sequences from 20
      mammalian and avian isolates and secondary structure predictions. The 54% alpha
      helical conformation predicted is in good agreement with CD results reporting 53
      71% content of alpha-helices. Despite the sequence divergence of mammalian and
      avian proteins, the secondary structure prediction of both shows a high degree of
      coincidence, according to the multiple sequence alignment. The proposed fold of
      HBc monomers is built from five alpha-helices. In dimers, pairs of two of those
      helices conform the protruding domain. The model also suggests the convergence of
      the region preceding the protamine domain around the sixfold symmetry axes. The
      model gives answers to most of the standing questions concerning the nucleocapsid
      assembly and antigenic behavior of HBc protein.

PMID- 9169230
TI  - Three-dimensional reconstruction with contrast transfer function correction from
      energy-filtered cryoelectron micrographs: procedure and application to the 70S
      Escherichia coli ribosome.
AB  - Cryoelectron microscopy provides the means of studying macromolecules in their
      native state. However, the contrast transfer function (CTF) makes the images and
      the three-dimensional (3D) maps derived from them difficult to interpret. We
      developed methods to determine the CTF from experimental data and to obtain a CTF
      corrected 3D reconstruction. The CTF correction and 3D reconstruction
      accomplished in one step make it easy to combine different defocus data sets and
      decrease the error accumulation in the computation. These methods were applied to
      energy-filtered images of the 70S Escherichia coli ribosome, resulting in a
      distortion-free 3D map of the ribosome at 1/24.5 A-1 resolution, as determined by
      the differential phase residual resolution criterion.

PMID- 9169231
TI  - Electron microscopic localization of lacZ expression in the proximal convoluted
      tubular cells of the kidney in transgenic mice carrying chimeric
      erythropoietin/lacZ gene constructs.
AB  - Regulated expression of the erythropoietin (EPO) gene in the adult kidney plays a
      key role in the regulation of erythropoiesis. However, uncertainty exists
      regarding the type of kidney cells involved in EPO gene expression. We previously
      showed by light microscopy that the lacZ reporter gene is expressed and inducible
      by hypoxia/anemia in the proximal convoluted tubular (PCT) cells of the kidneys
      of transgenic mice carrying the 5'-lacZ construct, in which the lacZ gene was
      placed downstream of a 7.0-kb mouse EPO gene segment containing 6.5 kb of the 5'
      flanking sequence. We, report here the light and transmission electron
      microscopic examination of lacZ expression in the kidneys of transgenic mice
      carrying the 5'-lacZ construct and two additional constructs carrying the 6.5-kb
      5'-flanking sequence with the body of the gene alone, or along with the 1.2-kb 3'
      flanking sequence. The electron microscopic analyses unequivocally demonstrated
      that lacZ under the regulatory control of the 6.5-kb 5'-flanking sequence with or
      without the body of the gene and the 1.2-kb 3'-flanking sequence was expressed
      predominantly in the proximal convoluted tubular cells of the kidney following
      hypoxia induction.

PMID- 9169232
TI  - Bio-Beads: an efficient strategy for two-dimensional crystallization of membrane
      proteins.
AB  - This work establishes the potential of Bio-Beads as a simple alternative to
      conventional dialysis for removing detergent and for obtaining 2D crystals of
      integral membrane proteins useful for structure analysis by electron
      crystallography. Kinetic and equilibrium aspects of removal of different
      detergents by adsorption onto hydrophobic Bio-Beads SM2 have been systematically
      investigated and extended to 2D crystallization of different prototypic membrane
      proteins, including: (a) Ca2+ ATPase from sarcoplasmic reticulum; (b) melibiose
      permease from Escherichia coli; (c) cytochrome b6f from Chlamydomonas
      reinhardtii. Different crystals could be produced from all protein preparations,
      with optical diffraction down to 20-25 A in negative stain.

PMID- 9169233
TI  - Rational design of complex formation between plasminogen activator inhibitor-1
      and its target proteinases.
AB  - Considerable progress in understanding the mechanism of inhibition of proteinases
      by serpins has been obtained from different biochemical studies. These studies
      reveal that stable serpin/proteinase complex formation involves insertion of the
      reactive-site loop of the serpin and occurs at the acyl-enzyme stage. Even though
      no three-dimensional structure of a serpin/proteinase complex is resolved,
      structural information is available on some of the individual compounds.
      Molecular modeling techniques combined with recently acquired
      biochemical/biophysical data were used to provide insight into the stable complex
      formation between plasminogen activator inhibitor-1 (PAI-1) and the target
      proteinases: tissue-type plasminogen activator, urokinase-type plasminogen
      activator, and thrombin. This study reveals that PAI-1 initially interacts with
      its target proteinase when its reactive-site loop is solvent exposed and thereby
      accessible for the proteinase. Stable complex formation, however, involves the
      insertion of the reactive-site loop up to P7 and results in a tight binding
      geometry between PAI-1 and its target proteinase. The influence of different
      biologically relevant molecules on PAI-1/proteinase complex formation and the
      differences in inhibition rate constants observed for the different proteinases
      can be explained from these models.

PMID- 9169234
TI  - Immunocytology shows the presence of tobacco etch virus P3 protein in nuclear
      inclusions.
AB  - Intracellular localization studies of various potyvirus proteins have been made
      in hope of finding clues to their function(s). Immunocytological studies
      localized many of the tobacco etch virus (TEV)-encoded proteins in infected
      cells. We used antiserum against the nonstructural P3 protein of TEV to determine
      the subcellular location of the P3 protein in ultrathin sections of virus
      infected cells. Immunogold labeling with the antiserum showed labels associated
      with nucleoli, nuclei, or NIs, Absorption of antiserum with purified NIs or P3
      protein resulted in no labeling. TEV NIs are known to contain a bifunctional
      genome-linked protein-viral proteinase (NIa-VPg) and RNA-dependent RNA polymerase
      (NIb). It appeared that the TEV P3 protein was a third nonstructural viral
      protein of NIs of TEV if the NIa-VPg is considered one protein. The presence of
      P3 in NIs was also supported by Western blot assays. P3 protein in the nucleolus
      and nucleus could indicate that it, too, is involved in early stages of viral
      replication.

PMID- 9169235
TI  - Crystallization and preliminary X-ray analysis of neuropsin, a serine protease
      expressed in the limbic system of mouse brain.
AB  - Neuropsin (M(r) 25032) is a serine protease expressed in the limbic system of
      mouse brain. It has been implicated in various neurological processes including
      formation of memory and may be important as a drug target in the treatment of
      epilepsy. The recombinant protein was produced using a baculovirus expression
      system and was purified. Two crystal forms were obtained by a hanging-drop vapor
      diffusion method with polyethylene glycol. Preliminary X-ray crystallographic
      analysis revealed that crystal form I belongs to triclinic space group P1 with
      unit cell dimensions a = 97.16 A, b = 97.12 A, c = 46.75 A and alpha = 99.17
      degrees, beta = 99.77 degrees, gamma = 117.35 degrees. Self-rotation function
      analysis of these data of form I indicates the position of a noncrystallographic
      threefold axis. There are six molecules in the crystallographic asymmetric unit.
      Crystal form II also belongs to triclinic space group P1 but has unit cell
      dimensions of a = 38.40 A, b = 55.16 A, c = 65.37 A and alpha = 95.38 degrees,
      beta = 89.98 degrees, gamma = 110.46 degrees with two molecules in the
      crystallographic asymmetric unit. Form II has a noncrystallographic twofold axis.
      Intensity data to 3.1 A resolution for form I and to 2.2 A resolution for form II
      have been collected.

PMID- 9169236
TI  - Cannibalism can be beneficial even when its mean yield is less than one.
AB  - Two types of adult-on-juvenile cannibalism are discussed and differentiated:
      those with "mean yield of cannibalism" greater than one, and those with mean
      yield less than one. Two extant models--one continuous and one discrete--in which
      cannibalism is beneficial only when the mean yield exceeds one are reviewed and
      compared. The discrete model is modified and analyzed to demonstrate that
      cannibalism can be beneficial even when the mean yield is less than one.

PMID- 9169237
TI  - Branching process models for mutant genes in nonstationary populations.
AB  - A deleterious gene achieves a population balance between the opposing forces of
      selection and mutation. In this paper we explore the nature of this stochastic
      balance when the surrounding normal population is not at equilibrium. Assuming
      that new mutations occur according to a Poisson process and thereafter evolve by
      the rules of a continuous time branching process, we derive explicit formulas and
      recurrence relations determining the probability distribution of the current
      number of mutant individuals. In fact, we compute expectations for a variety of
      interesting random variables for genetic models involving autosomal dominant and
      X-linked diseases. We can also handle haplotype information on linked markers.
      This feature will be especially helpful in understanding the linkage
      disequilibrium strategy of positional cloning in population isolates. In the
      presence of exponential growth of the normal population, our formulas reduce to
      the evaluation of certain Laplace transforms.

PMID- 9169238
TI  - Deleterious mutations, variable epistatic interactions, and the evolution of
      recombination.
AB  - In this paper, we examine the conditions that allow increased recombination to
      evolve in the presence of recurrent deleterious mutation. We focus on a three
      locus model first studied by Feldman et al. (1980), which follows the dynamics of
      a modifier locus that alters the recombination rate between two loci subject to
      deleterious mutation. Although Feldman et al. (1980) indicated that increased
      recombination might be favored if there is diminishing-returns epistasis, we show
      that alleles that increase the recombination rate can only invade if there is
      synergistic epistasis between the loci under selection. Even with synergistic
      epistasis, evolution at the modifier locus will lead to decreased recombination
      if the modifier locus is loosely linked and epistasis is strong. Using the multi
      locus analysis of Barton (1995), we show that variability among loci in the sign
      and strength of epistasis further decreases the parameter space over which
      increased recombination may evolve. We conclude that, even with negative
      epistasis, increased recombination may only be favored when linkage is tight,
      especially if, as seems likely, epistatic interactions are highly variable among
      loci.

PMID- 9169239
TI  - Sky above clouds. Mental health in later life.

PMID- 9169240
TI  - The prognosis of depression in old age.
AB  - The authors sought to determine the prognosis of depression in old age by
      reviewing original literature on this topic from three computer databases. All
      reports used at least 20 patients over age 60, followed up for at least 1 year,
      with affective status as outcome, and a quantitative meta-analysis was performed
      to combine results. Sixteen hospital-based and five community-based studies were
      selected, involving 1,487 and 249 depressed subjects, respectively. Most studies
      had serious methodological limitations. For combined results, 60% of patients in
      the hospital-based studies were well or had relapses-with-recovery, and 14%-22%
      were continuously ill; 19%-34% of community subjects were well; 27% were
      continuously ill, and most of the remainder had died. Physical illness, cognitive
      impairment, and severe depressive symptoms were frequently but inconsistently
      related to poor prognosis. Future studies must attend to composition of study
      populations and outcome assessment and control of extraneous prognostic factors.

PMID- 9169241
TI  - Quantitative anatomic measures and comorbid medical illness in late-life major
      depression.
AB  - The authors examined the individual and relative roles of atrophy, comorbid
      medical illness, and cerebrovascular risk factors in the pathogenesis of late
      life major depressive disorder (MDD). They used magnetic resonance imaging
      techniques to study 28 subjects with late-life MDD, 29 healthy control subjects,
      and 34 subjects with probable dementia of the Alzheimer type (DAT). Depressed
      subjects showed increases in cerebrospinal fluid volumes comparable to the DAT
      group but significantly different from control subjects. High-intensity signals,
      but not measures of atrophy correlated significantly with cerebrovascular risk
      factor scores. A logistic regression revealed that both brain atrophy and medical
      illness are associated with an increased risk of developing MDD. Data suggest
      that both atrophy and comorbid medical illness increase the likelihood of
      developing MDD in late life.

PMID- 9169242
TI  - Assessment of behavioral symptoms in community-dwelling dementia patients.
AB  - The authors compared the CERAD Behavior Rating Scale for Dementia (CBRSD) with
      the Cohen-Mansfield Agitation Inventory (CMAI) for their ability to detect
      behavioral symptoms in community-dwelling dementia patients with mild-to-moderate
      global impairment. Both instruments were administered to caregivers of 33
      cognitively impaired patients seen in a dementia clinic at initial evaluation or
      follow-up visit. Endorsement of a higher percentage of items on the CBRSD than
      the CMAI suggests greater sensitivity of this instrument to the behavioral
      symptoms seen in community-dwelling patients. There was good correlation between
      the number of items endorsed on both scales but not between subscales of the CMAI
      and factors of the CBRSD that appeared related to agitation. Thus, the CBRSD and
      CMAI both seem to measure behaviors that occur in dementia patients, but the
      CBRSD's two agitation-related factors do not appear to measure agitation as
      defined by the CMAI.

PMID- 9169243
TI  - Cognitive deficits and psychopathology in elderly schizophrenic patients.
AB  - The authors investigated the syndromal and cognitive profiles of 25 DSM-III-R
      older schizophrenic inpatients with continuous acute psychotic symptoms and
      compared them with 20 younger schizophrenic patients by means of a
      multidimensional assessment battery. Subjects were medically well and without
      neurological comorbidity and were comparable in length of current hospitalization
      and medication regimens. There were no significant differences between the two
      groups on various symptom rating scores or on neurological variables. The older
      group's mean scores for various cognitive measures did not reach the value for
      senile dementia. They also scored significantly better on a memory test and on
      formal cognitive functions. These findings support the notion of a stable
      encephalopathy, rather than a dementia-like process, underlying the course of the
      illness. Authors discussed limitations and implications of these findings.

PMID- 9169244
TI  - Psychosocial predictors of mental health in a population of elderly women. Test
      of an explanatory model.
AB  - The understanding of adjustment to aging calls for models that illustrate the
      interaction of psychosocial and health factors. The authors surveyed a group of
      retired Catholic sisters, examining the contributions of psychosocial factors and
      religiousness to life satisfaction, psychological distress, and depression. Life
      satisfaction was best explained by a four-factor model that included mastery,
      social support, physical functioning, and religious commitment. General level of
      distress was best predicted by physical functioning, social support, and mastery,
      but not religiousness. Depression, on the other hand, was predicted by mastery,
      social support, and religious commitment. These data are consistent with a
      proposed model in which internal, external, and coping resources mediate the
      psychological impact of impaired functional status.

PMID- 9169245
TI  - The posttreatment illness course of depression in bereaved elders. High
      relapse/recurrence rates.
AB  - Losing close attachments through death in late life is common and can lead to
      depression. Previous work has shown the clinical benefits of treating these
      depressions. This article describes the 2-year course of 53 elderly subjects with
      bereavement-related depression after responding to various treatments. Forty-six
      patients experienced a full response to acute treatment, but 36% experienced
      relapse or recurrence. This finding suggests that the treatment response in
      depressed bereaved older patients is more brittle than expected.

PMID- 9169246
TI  - A double-blind comparison of trazodone and haloperidol for treatment of agitation
      in patients with dementia.
AB  - The authors compared the efficacy and side effects of trazodone and haloperidol
      for treating agitated behaviors associated with dementia. Twenty-eight elderly
      patients with dementia and agitated behaviors were randomly assigned to double
      blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day)
      for 9 weeks. There was no significant difference in improvement between the
      medication groups. Adverse effects, however, were more common in the group
      treated with haloperidol. Improvement in individual areas suggested that
      repetitive, verbally aggressive, and oppositional behaviors responded
      preferentially to trazodone, whereas symptoms of excessive motor activity and
      unwarranted accusations responded preferentially to haloperidol. These results
      indicate that moderate doses of trazodone and haloperidol are equally effective
      for treatment of overall agitated behaviors in patients with dementia, but
      specific symptoms may respond preferentially to a particular agent.

PMID- 9169247
TI  - An open pilot study of citalopram for behavioral disturbances of dementia. Plasma
      levels and real-time observations.
AB  - Citalopram, in European studies, has shown some early promise for treatment of
      poststroke depression and behavioral complications of dementia. An open pilot
      study of citalopram was conducted in 16 patients with dementia and behavioral
      disturbances. Citalopram was well tolerated by 13 of the patients, and 9 had a
      clinically impressive response. A significant overall mean reduction in
      disruptive vocalizations was observed by means of a novel technique of computer
      assisted real-time observation. The mean citalopram plasma level-to-dose ratio
      was found to be twice that previously reported in younger patients. These pilot
      findings should encourage future placebo concentration-controlled trials.

PMID- 9169248
TI  - Late-onset major depression with delusions after metoclopramide treatment.
AB  - The authors describe major depression with delusions occurring for the first time
      in an elderly man receiving metoclopramide and review the literature concerning
      metoclopramide and depression.

PMID- 9169249
TI  - Fluoxetine discontinuation in elderly dysthymic patients.
AB  - A group of 23 elderly outpatients with dysthymic disorder participated in a 13
      week fluoxetine trial. Twelve responders received open continuation treatment and
      subsequently discontinued fluoxetine (mean: 32 weeks on medication). During the
      24 weeks after discontinuation, 6 of the 12 patients relapsed. Clinical features,
      dose, and duration of fluoxetine treatment were not predictive of relapse. The
      50% relapse rate in this small sample is lower than that reported in young adult
      dysthymic patients but is high enough to warrant clinical caution.

PMID- 9169250
TI  - The apolipoprotein E epsilon 4 allele is associated with increased behavioral
      disturbance in Alzheimer's disease.

PMID- 9169251
TI  - Comparative bioavailability of aspirin and paracetamol following single dose
      administration of soluble and plain tablets.
AB  - In this study, the bioavailability of aspirin and paracetamol was compared in
      plain and soluble combination formulations in fasting, healthy volunteers. Blood
      samples were taken and Cmax, Tmax and AUC measured at various times following
      administration of single doses of the two formulations in 12 subjects. The
      rapidity of uptake of aspirin following administration of a soluble formulation
      suggests significant absorption from the stomach. There was no significant
      difference in the pharmacokinetic parameters of paracetamol derived from a
      soluble or plain formulation. A comparison of the uptake of aspirin from the
      soluble aspirin formulation with paracetamol from either plain or soluble tablets
      showed that aspirin entered the plasma and achieved peak levels significantly
      more quickly. However, the half life of paracetamol was significantly longer than
      that of aspirin. These findings suggest that onset of analgesia should be more
      rapid following dosing with soluble aspirin, a conclusion supported by
      comparative efficacy studies conducted with differing formulations of aspirin.

PMID- 9169252
TI  - A comparative study of Ocusert Pilo 40, intensive pilocarpine and low-dose
      pilocarpine in the initial treatment of primary acute angle-closure glaucoma.
AB  - Acetazolamide and pilocarpine have a central role in the initial management of
      primary acute angle closure glaucoma (PACG), but there is no consensus concerning
      their mode of delivery, as borne out by a recent survey of senior UK
      ophthalmologists reported below. Ocusert Pilo 40 was developed to remain in situ
      releasing pilocarpine for up to one week. In view of its potential advantages, a
      trial of Ocusert Pilo 40's efficacy in PACG was conducted. In two separate
      controlled studies, eyes diagnosed with PACG were randomised to receive Ocusert
      Pilo 40, and either an intensive pilocarpine regimen or a low-dose pilocarpine
      treatment. All patients also received Diamox 500 mg i.v. Two hours after starting
      topical treatment, the study was terminated and ocular and systemic response to
      treatment and the eventual outcome were assessed. In both studies, intravenous
      Diamox caused a fall of intraocular pressure (IOP) within 30 min. Over the
      treatment period, a comparable reduction in IOP was seen in the Ocusert-treated,
      the intensive-pilocarpine-treated, and the low-dose-pilocarpine-treated groups.
      No damage to the corneas were observed.

PMID- 9169253
TI  - Clinical evaluation of indomethacin-containing patches for osteoarthritis and
      extremity trauma.
AB  - Seventy-eight patients, aged 12-87 years, with osteoarthritis or extremity
      trauma, attached one indomethacin patch (containing 96 mg indomethacin) to the
      most symptomatic site twice daily. The final overall treatment outcome was
      excellent in 52% of the osteoarthritic patients and in 82% of the trauma
      patients, good in 27% and 13%, and fair in 3% and 0%, respectively. Side effects
      were reported by 4% of the patients. It is concluded that indomethacin-containing
      patches were effective and well-tolerated for the treatment of osteoarthritis and
      extremity trauma.

PMID- 9169254
TI  - Assessment of the efficacy of a last-generation polyvalent immunoglobulin in the
      treatment of idiopathic thrombocytopenic purpura.
AB  - High-dose intravenous immunogammaglobulin (h.d.IgG) has been proposed as a
      treatment of idiopathic thrombocytopenic purpura (ITP), but the clinical effect
      is usually short and adverse reactions have been reported in clinical studies
      using different immunoglobulin (Ig) preparations. In this study, the efficacy of
      a last-generation polyvalent immunoglobulin in the treatment of ITP in adults and
      the incidences of adverse reactions of this therapy were evaluated. The reported
      data were based on various clinical and laboratory parameters evaluated before,
      during and after therapy, with a follow-up of 6 months. The data showed
      administration of 400 mg/kg d of intravenous polyvalent intact IgG for 5 days
      significantly increased the platelet count in all 15 patients, the maximum level
      occurring on Day 10 and being maintained in some patients for 6 months. Its very
      rapid onset of action suggests it may be useful for correcting life-threatening
      thrombocytopenia where bleeding complicates the clinical course, and for severe
      ITP in seriously immunosuppressed or infected patients in whom corticosteroids or
      immunosuppressive agents cannot be safely administered. The treatment was also
      well tolerated. In conclusion, polyvalent Ig may be useful in ITP steroid
      refractory patients; further studies are required to evaluate clinical-laboratory
      parameters related to the long-term response of patients.

PMID- 9169255
TI  - Results of a postmarketing drug monitoring survey with a polidocanol-urea
      preparation for dry, itching skin.
AB  - In an open multicentre drug monitoring survey, 1611 patients with atopic
      dermatitis, contact eczema, dry eczema, psoriasis and pruritus were treated with
      a preparation containing 5% urea and 3% polidocanol (laurylmacrogol). To monitor
      the course of treatment, three examinations were performed, one at the start of
      therapy and two more at intervals of approximately two weeks. A marked
      improvement in the status of the skin was observed during treatment. A marked
      regression occurred in the principal signs of dry skin--scaling, dryness and
      roughness. Troublesome itching was also greatly reduced. Almost half of the
      patients (48.9%) were free of itching at the end of the observation period.
      Adverse drug effects arose in only 2.8% of cases, and were mostly smarting,
      itching and irritation. No intolerance reactions were observed in children under
      six years. At the end of the observation period the skin status was judged, by
      both the doctors and the patients as 'good' or 'very good' in almost 90% of
      cases. Furthermore, the assessment with regard to the regression of itching was
      almost identical.

PMID- 9169256
TI  - A pilot study of the effect of the glycosaminoglycan sulodexide on
      microalbuminuria in type I diabetic patients.
AB  - Fifteen out-patients with type I diabetes mellitus and microalbuminuria (mean +/-
      SEM: 95.4 +/- 13.9 micrograms/min), were administered the glycosaminoglycan
      sulodexide, with the aim of investigating its influence on the rate of albumin
      excretion. Sulodexide was given intramuscularly in a dose of 600
      lipoproteinlipase releasing units/day for three weeks. Albumin excretion was
      measured before dosing, at weekly intervals during dosing and also during the
      subsequent follow-up period of six weeks. Sulodexide yielded a clear-cut and
      statistically significant lowering of albumin excretion after the first week of
      treatment (from 95.4 +/- 13.9 micrograms/min to 53.6 +/- 11.1 micrograms/min; p =
      0.0055); albumin excretion was further decreased after three weeks of treatment
      (26.5 +/- 6.05 micrograms/min; p = 0.0007) and was maintained during the follow
      up period, at the end of which the mean value was still significantly lower than
      at baseline (39.6 +/- 10.3 micrograms/min; p = 0.01). Sulodexide short-term
      administration did not influence the routine haematological, haematochemical and
      coagulative tests performed contemporaneously. Patients' compliance with
      treatment was very good and no adverse events were reported.

PMID- 9169257
TI  - Gallery of medical devices.
AB  - This article provides an overview of the multitude of medical devices used in
      patients from head to toe. Simple line drawings show a wide assortment of medical
      devices. These drawings and the accompanying short descriptions are to be used
      for quick reference to identify some of the more common medical devices that are
      certain to appear on everyday radiographs. There is an extensive bibliography for
      the reader to obtain more detailed information about a particular device or
      medical apparatus. Knowing the specific name of a device is nearly impossible and
      is really not necessary, in particular, the eponyms attached to all manner of
      orthopedic apparatus. Many device names have evolved from their original meaning.
      What is important is the device's function and the recognition of its presence,
      as well as an understanding of its use and potential complications.

PMID- 9169258
TI  - The 4-hour glove for epoxy and acrylic monomer (dental and orthopedic personnel)
      and glyceryl monothioglycolate (hairdressers)

PMID- 9169259
TI  - A dermatologic diary. Portrait of a practice.

PMID- 9169260
TI  - Alopecia areata.
AB  - Alopecia areata is a frequent and physiologically compelling form of hair loss.
      It is most common in children and young adults, but can affect people of any age.
      Although it is usually limited to patches on the scalp, it may involve the entire
      scalp and other hair-bearing regions of the body. It may be associated with
      autoimmune disorders, especially of the thyroid. Its effective treatment often
      poses a difficult challenge.

PMID- 9169261
TI  - Cutaneous heparin necrosis in a patient with heterozygous protein S deficiency.
AB  - A patient with heterozygous protein S deficiency experienced cutaneous necrosis
      following subcutaneous heparin administration. Deficiencies of both protein C and
      protein S, known risk factors for the more frequently encountered coumarin
      necrosis, may predispose patients to this complication of heparin therapy as
      well. The putative association of protein S deficiency with cutaneous heparin
      necrosis could not be proven, however, since attempts to reproduce the heparin
      necrosis were unsuccessful.

PMID- 9169262
TI  - Diving suit dermatitis: a manifestation of Pseudomonas folliculitis.
AB  - Pseudomonas aeruginosa causes a variety of cutaneous infections. Pseudomonas
      folliculitis has been associated with a number of activities, particularly
      bathing in contaminated water and the use of contaminated objects while bathing.
      We present two unique cases in which the subjects noted Pseudomonas folliculitis
      after recreational use of diving suits.

PMID- 9169263
TI  - Onychomycosis.
AB  - Treatment options for onychomycosis are expanding, making accurate and prompt
      diagnosis of greater importance. Diagnosis of onychomycosis can be made by direct
      examination of potassium hydroxide-prepared nail clippings, culture, and
      histologic examination. We compared culture of nail clippings to histologic
      examination and show that histologic examination is a quick and reliable
      alternative.

PMID- 9169264
TI  - Cephalexin rash in infectious mononucleosis.
AB  - The ampicillin rash occurring in cases of infectious mononucleosis is well
      documented. Similar phenomena have also been observed with other antibiotics. The
      case of a patient with infectious mononucleosis treated with cephalexin who later
      showed a rash is presented and the previous literature is reviewed. The rash seen
      in this patient, who was treated with cephalexin, may be similar to the rash seen
      with ampicillin treatment of patients with infectious mononucleosis. The
      mechanism by which these eruptions occur is not completely understood, although
      there are many interesting theories. Perhaps rashes during infectious
      mononucleosis in association with other antibiotics are actually more common, but
      just not recognized. A heightened awareness of this possibility may therefore
      lead to recognition of more cases and further understanding of this entity.

PMID- 9169265
TI  - A case of chrysiasis.
AB  - Chrysiasis and chrysoderma are terms used to describe permanent pigmentation of
      the skin due to the parenteral administration of gold salts. A case of
      chrysiasis, including a photomicrograph of the characteristic orange-red
      birefringence of gold in tissue when viewed under cross-polarized light, is
      presented. A review of the literature on the pathogenesis of the pigmentation
      seen in this disorder is also presented.

PMID- 9169266
TI  - Reactivation of oral-lingual herpes by chlorinated swimming pool water. A case
      report.

PMID- 9169267
TI  - Blue rubber bleb nevus syndrome associated with diffuse angiokeratoma.
AB  - We report a case of the association of blue rubber bleb nevus syndrome with
      diffuse angiokeratoma, without any evidence of enzyme deficiencies. The lesions
      of both disorders had a late-onset appearance.

PMID- 9169268
TI  - Lesion size is a factor for determining the rate of port-wine stain clearing
      following pulsed dye laser treatment in adults.
AB  - Seventy-four adult patients with facial, truncal, and extremity port-wine stains
      (PWS) were treated with the flashlamp-pumped pulsed dye laser (PDL) with laser
      output ranging from 6.0 to 7.5 J/cm2. Response to treatment was analyzed by
      comparing the area of involvement following each treatment with the area of
      involvement measured in the first treatment session. All the PWS responded with
      25 to 90 percent lightening, and 85.1 percent of patients achieved 25 percent
      clearing. However, only 36.5 percent achieved 50 percent clearing, and none of
      the patients achieved 100 percent clearing. None of four patients with PWS
      greater than 100 cm2 achieved 50 percent clearing following a mean of 17.2 +/-
      5.7 treatments. These data emphasize the importance of objectively documenting
      clinical response to PDL treatment of PWS. Adult patients need to be made aware
      that complete clearing may not be obtainable by PDL treatment alone. This is
      especially important for adult patients with PWS larger than 100 cm2.

PMID- 9169269
TI  - Proposed guidelines for speakers discussing medications and other products.

PMID- 9169270
TI  - A patient with cutaneous T-cell lymphoma and dermatomyositis.
AB  - Dermatomyositis in adults has been associated with a variety of internal
      malignancies. We present a case of a patient with dermatomyositis and cutaneous T
      cell lymphoma.

PMID- 9169271
TI  - Skin metastases from prostate cancer associated with malignant melanoma.
AB  - A 66-year-old man, admitted to the hospital for prostatic carcinoma, presented
      with a nodular lesion located on the presternal region and a small nodule (0.5 cm
      in diameter) simulating a scalp sebaceous cyst located on the scalp. Moreover, an
      irregular darkbrown lesion was observed on the left side of the abdomen, and a
      brownish macula was also present on the presternal region. Histologic examination
      of the two nodular lesions revealed cutaneous metastases from prostatic
      carcinoma. The pigmented lesion, localized on the abdomen, proved to be a
      superficial spreading melanoma with a maximal depth of 1.36 mm. Histologic
      examination of the brownish lesion on the presternal region revealed nevus cell
      nests within the epidermis and in the dermis. We discuss the propensity of
      developing a secondary cancer in a patient with a primary malignancy.

PMID- 9169272
TI  - Major aphthous-like ulcers in two patients infected with human immunodeficiency
      virus.
AB  - Two patients infected with human immunodeficiency virus (HIV) presented with
      persistent, large, and painful oral ulcers. Results of cultures and examination
      of a biopsy specimen were negative for infection and malignancy. Major aphthous
      like ulcers should be considered in the differential diagnosis of oral ulcers in
      the HIV-infected patient.

PMID- 9169273
TI  - Topical treatment of psoriasis with fludarabine.
AB  - Fludarabine is not used as a topical medication for the treatment of psoriasis.
      In this study we evaluated the efficacy of fludarabine for this purpose. Four
      male patients with two bilaterally symmetrical psoriatic plaques were treated
      with 0.2 percent topical fludarabine in aquaphor (fludarabine site) or aquaphor
      alone (control site). The fludarabine and control sites were compared before and
      during the study on a weekly basis for three weeks by degree of redness,
      scaliness, and thickness on a scale of 0 to 4 (0, not apparent; 4, very
      apparent). The results of our study showed no significant difference between
      topical fludarabine and aquaphor in the treatment of psoriatic plaques.

PMID- 9169274
TI  - Immunotherapy of warts with masoprocol cream.

PMID- 9169275
TI  - Geographic information systems, spatial network analysis, and contraceptive
      choice.
AB  - How does family planning accessibility affect contraceptive choice? In this paper
      we use techniques of spatial analysis to develop measures of family planning
      accessibility, and evaluate the effects of these geographically derived measures
      in a multilevel statistical model of temporary method choice in Nang Rong,
      Thailand. In our analyses we combine spatial data obtained from maps and Global
      Positioning System (GPS) readings with sociodemographic data from surveys and
      administrative records. The new measures reveal (1) important travel time effects
      even when family planning outlets are close by; (2) independent effects of road
      composition; (3) the relevance of alternative sources of family planning supply;
      and (4) the importance of the local history of program placement.

PMID- 9169276
TI  - A mixture model for duration data: analysis of second births in China.
AB  - In this paper we introduce a mixture model in which we combine logistic
      regression and piecewise proportional hazards models for analysis of duration
      data. The model allows simultaneous estimation of two sets of effects of
      covariates: one of the probability of an event and the other of the timing of the
      event. We illustrate the application of the model through an analysis of the
      effects of women's characteristics and of the acceptance of a one-child
      certificate on the birth of second children in China. Both factors affect the
      probability of having a second child, but only the acceptance of a one-child
      certificate has a significant and strong effect on the second-birth interval.

PMID- 9169277
TI  - The number of Israeli immigrants in the United States in 1990.
AB  - In this paper we estimate the size of several categories of "Israeli" immigrants
      in the United States. According to the 1990 U.S. census, there were about 95,000
      Israeli-born immigrants in the United States in that year. Using the language and
      ancestry information available in the Public Use Microdata Sample (PUMS) of the
      1990 census, we estimate that of this total, about 80,000 are Jews and 15,000 are
      Palestinian Arabs born in Israel. In addition to the Israeli-born, we present a
      range for the number of Jewish immigrants from Israel who are not Israeli-born
      (about 30,000-56,000). Thus our estimate for the total number of Jewish
      immigrants from Israel in the United States in 1990 is between 110,000 and
      135,000. Fertility information available in the PUMS, also enable us to provide
      estimates for the number of second-generation Israelis in the United States in
      the 1990 (about 42,000). Finally, using both the 1980 and 1990 PUMS, we provide
      estimates for the rate of return migration among Israeli-born Jewish immigrants
      in the United States.

PMID- 9169278
TI  - Changing patterns of internal migration 1970-1990: a comparative analysis of Jews
      and whites in the United States.
AB  - Independently conducted yet complementary sets of data from the 1970/1971 and
      1990 National Jewish Population Surveys and the U.S. censuses of the same years
      were used to analyze changes in the internal migration of Jews and whites during
      the periods 1965-1970(1971) and 1985-1990. Interstate lifetime and five-year
      migration rates among Jews increased to levels significantly surpassing those of
      whites. Adjusting Jewish migration rates for the educational achievement of their
      white counterparts did not have much of an effect on lifetime migration or on the
      recent migration of the 1970/1971 Jewish population; however, it accounted
      meaningfully for the migration propensities of Jews in the period 1985-1990.
      These findings suggest that socioeconomic status has begun to play a larger role
      in promoting different migration patterns than in promoting ethnic group
      differences. Further, the direction of Jewish migrations followed those of whites
      (i.e., from the North-east and Midwest to the South and West): and due to their
      higher migration rates, Jews have considerably narrowed the regional distribution
      differences between themselves and whites. I interpret these results as evidence
      of the weakening role of ethnicity in present-day America.

PMID- 9169279
TI  - The mobility experience and neighborhood attachment.
AB  - In this study, I consider variables associated with an individual's most recent
      move into his or her current residence as predictors of neighborhood attachment.
      Using the 1978-1979 Seattle Community Attachment Survey, I find that elements of
      the mobility experience such as an individual's past history of migration, the
      motivations for moving, the amount of time involved in the move, and the distance
      traveled during the move have an effect on short- and long-term neighborhood
      attachment patterns independent of residential stability and investment
      predictors. The findings imply that psychosocial factors such as familiarity with
      the environment, increased premove exposure to the new environment, and perceived
      control during instances of transition have some impact on individuals' postmove
      attitudes and behaviors, and suggest that researchers should look beyond
      traditional "types of people" explanations of urban neighborhood attachment.

PMID- 9169280
TI  - Measuring immigrant wage growth using matched CPS files.
AB  - Cross-sectional estimates of immigrant wage growth have painted an optimistic
      picture of the ability of immigrants to adapt to the U.S. labor market: Studies
      using cross-sectional data have generally found the wage growth of immigrants to
      exceed that of the native born. This optimistic picture of immigrant economic
      assimilation was challenged by the important finding that compared to earlier
      immigrant cohorts, recent immigrants started at much lower wages. As such, the
      high wage growth of immigrants relative to the native born measured in cross
      sectional data may simply be the spurious result of declining immigrant earnings
      ability. In this paper, we match Current Population Survey samples so that the
      wages of individual immigrant and native-born men can be followed for one year.
      We find that the wage growth of immigrants does exceed that of the native born.
      The general finding of faster immigrant wage growth also holds when imposing the
      foreign-born geographic distribution upon natives, but not when imposing the
      native-born geographic distribution on the foreign born-a result consistent with
      some theories of immigrant assimilation. In each comparison, however, the actual
      wage growth of immigrants relative to natives is similar to the predictions of
      cross-sectional regressions. This similarity suggests that either there is no
      cohort quality bias in the cross-sectional estimates of immigrant wage growth, or
      that there has been a coincidental increase in immigrant wage growth as the entry
      wages of immigrants have fallen.

PMID- 9169281
TI  - Measuring spatial focusing in a migration system.
AB  - Equality indexes used in other geographical contexts may be used to gauge the
      degree of spatial focusing in an entire migration system or within the gross in-
      and out-migration fields of specific regions. They provide useful indicators of
      overall shifts in the patterns of interregional migration and can help give
      insight into the population redistributive roles played by specific regions.
      Perhaps the most common equality index used to measure income distribution is the
      Gini coefficient, yet it appears almost never to have been applied in migration
      research. In this paper we set forth a variety of Gini indexes to be used for
      different migration analyses and illustrate their application with recent data on
      U.S. interstate movements. We argue that the Gini index provides some singularly
      useful insights that differ from those afforded by other measures more commonly
      found to date in the migration analyst's tool kit.

PMID- 9169282
TI  - Breaking the racial barriers: variations in interracial marriage between 1980 and
      1990.
AB  - Using PUMS data from the 1980 and the 1990 U.S. Census, I apply log-linear models
      to examine interracial marriage among whites, African Americans, Hispanics, and
      Asian Americans. Rarely, but increasingly between 1980 and 1990, interracial
      marriage of whites occurs most frequently with Asian Americans, followed by
      Hispanics, and then by African Americans. Interracial marriage tends to be
      educationally homogamous and the odds of interracial marriage increase with
      couples' educational attainment. Among interracially married couples with
      different educational attainments, both men and women from lower status racial
      groups but with high education levels tend to marry spouses from a higher status
      racial group with low education levels.

PMID- 9169283
TI  - Family dissolution, family reconstitution, and children's educational careers:
      recent evidence for Sweden.
AB  - Both longitudinal and cross-sectional analyses on a large and recent Swedish data
      set demonstrate that, compared to children in intact families, children who have
      experienced family dissolution or reconstitution show lower educational
      attainment at age 16. Time constraints do not seem to be an important mechanism
      behind the negative effect of separation. Economic deprivation affects children's
      attainment negatively, but downward social mobility appears to be an even more
      important causal mechanism: Losing the parent with the higher social position
      probably reduces social capital and aspirations. When we control for
      socioeconomic characteristics, a small net effect of separation and
      reconstitution remains.

PMID- 9169284
TI  - Household structure and childhood immunization in Niger and Nigeria.
AB  - In this study, we use data from the Demographic and Health Surveys to examine the
      relationship between household structure and childhood immunization in Niger and
      Nigeria. We show that household structure is an important determinant of
      childhood immunization in Nigeria: Children from nuclear, elementary polygynous,
      and three-generational households are worse-off than those from laterally
      extended households. However, the lower odds of full immunization among children
      from three-generational and elementary polygynous households are attributable to
      low economic status and low maternal education levels, respectively. In Niger,
      household structure does not have a significant effect on children's likelihood
      of being fully immunized.

PMID- 9169285
TI  - Lamotrigine pharmacokinetics in patients receiving felbamate.
AB  - Drug interactions can significantly complicate the management of patients
      receiving multiple medications. It is essential therefore that potential
      pharmcokinetic interactions be evaluated as new antiepileptic medications are
      introduced. Lamotrigine (LTG) is a recently marketed medication whose
      pharmacokinetics are significantly influenced by concomitant drugs. Felbamate
      (FBM), another relatively new antiepileptic agent has been associated with
      multiple interactions including both enzyme induction and inhibition. The purpose
      of the present pilot study was to evaluate potential differences in lamotrigine
      kinetics in six patients concomitantly receiving FBM compared to five patients
      receiving lamotrigine as monotherapy. There was no statistically significant
      differences in either apparent LTG oral clearance (0.026 +/- 0.005 vs. 0.024 +/-
      0.01 l/kg per h, respectively), or in mean elimination half-life (33.7 +/- 7.5
      vs. 40.2 +/- 15.05 h, respectively). Oral clearance values in our patients are
      also consistent with data reported previously in the literature. Data from this
      pilot study suggest that a marked effect of FBM upon lamotrigine pharmacokinetics
      is unlikely.

PMID- 9169286
TI  - Brain creatine kinase reaction rates and reactant concentrations during seizures
      in developing rats.
AB  - Brain creatine kinase (CK) catalyzed phosphorus fluxes between phosphocreatine
      (PCr) and ATP and changes in reactant concentrations were measured using [31P]
      nuclear magnetic resonance spectroscopy ([31P]NMR) before and during
      pentylenetetrazole-induced seizures in 7 and 21 day old rats. The CK rate
      constants measured before seizures were three times higher in the older than in
      the younger rats. The rate constants increased 60% during seizures in the older
      rats but did not change or decreased in the younger. Small decreases in PCr were
      seen during seizures at both ages. A small decrease in ATP was seen at 7 days but
      not at 21 days.

PMID- 9169287
TI  - Effects of neocortical implants of cobalt and other seizure-inducing metals on
      brain C-14 2-deoxyglucose uptake.
AB  - Nine days after insertion of a pure cobalt metal rod into the visual cortex,
      regions of increased 2-DG uptake are observed both in relatively normal Nissl
      staining tissue lying around the implant site and in the connecting dorsal
      lateral geniculate nucleus of the thalamus. These hypermetabolic regions have
      been claimed to be the metabolic 'signatures' of tissue made epileptogenic by the
      cobalt. The present study showed, however, that while the 'dark patches' develop
      following posterior cortex implants, they do not appear after anterior cortex
      cobalt implants. Moreover, the dark patches were not detectable after cortical
      implants of other seizure-inducing metals such as antimony and nickel. These new
      findings indicate that the dark patches occur too idiosyncratically to make them
      the metabolic 'signatures' of tissue made epileptic by cobalt.

PMID- 9169288
TI  - Effect of topiramate on attention.
AB  - Impaired attention is a frequently reported side effect of anti-epileptic
      medication, as well as a frequent general complaint of epilepsy. It is thus
      important to evaluate the effect of new medications on attention processes.
      Attention was assessed weekly in ten subjects receiving topiramate over a 3 month
      period. Attention was evaluated with digit span, a widely used index of
      attention. Different number sequences were constructed and randomized to allow
      for repeated use. Four of nine subjects showed significant correlations between
      topiramate dosage and forward digit span measured weekly, such that higher dosage
      was associated with poorer attention. The average topiramate dosage and seizure
      reduction did not differ between these subjects and those who did not show a
      significant relationship.

PMID- 9169289
TI  - Blockade of spreading depression in chronic epileptic rats: reversion by
      diazepam.
AB  - Following pilocarpine-induced status epilepticus, rats become chronically
      epileptic showing 2-3 spontaneous recurrent seizures per week. The aim of this
      work was to verify the characteristics of spreading depression (SD) in these
      chronic epileptic rats (n = 16). SD was evoked in one point of the frontal cortex
      by topical application of KCl solution at 20 min intervals, and recordings were
      made in two points over the parietal cortex (a 'near' point and a 'remote' one,
      about 3 and 8 mm posterior to the stimulating region, respectively). In all
      control animals (n = 10), KCl stimulation elicited SD which in 100% of the cases
      propagated regularly to the two recording points. In the chronic epileptic rats
      only about 50% of the KCl applications were effective in eliciting SD, detected
      at the 'near' recording point. Of these, only 3% propagated to the 'remote'
      recording point. In eight of the above epileptic rats, diazepam (5-10 mg/kg,
      i.v.) was injected after 1-2 h of recording, when SD incidence in response to KCl
      stimulation has been established. After diazepam, the incidence of SDs
      propagating regularly to the 'near' and to the 'remote' recording points
      increased significantly, (132 and 53 SDs, respectively, out of 139 KCl
      stimulations), as compared with the incidence in the pretreatment period (33 and
      1, respectively, out of 63 stimulations; P < 0.005). These data indicate an
      impairment in the susceptibility to cortical SD in chronic epileptic rats
      suggesting modifications in cortical excitability in the pilocarpine model of
      epilepsy. They also indicate a facilitatory effect of diazepam on SD, confirming
      previous observations in non-epileptic rats.

PMID- 9169290
TI  - Preclinical characterization of MDL 27,192 as a potential broad spectrum
      anticonvulsant agent with neuroprotective properties.
AB  - The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL
      27,192) was evaluated in a variety of rodent models to assess its anticonvulsant
      profile and its potential neuroprotective activity. MDL 27,192 demonstrated
      anticonvulsant activity in a wide range of epilepsy models that are genetically
      based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse;
      spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS),
      electrically-based (MES seizures in mice and rats, corneally-kindled seizures in
      rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic
      acid, quinolinic acid and strychnine). When compared to valproate, orally
      administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and
      showed a safety index one to three-fold greater. Following a timed intravenous
      administration of PTZ to mice, MDL 27,192, but not phenytoin or carbamazepine,
      consistently increased the latencies to first twitch and clonus. MDL 27,192 was
      active in a genetic model of absence epilepsy, the GAERS rat model. These data
      indicate that MDL 27,192 likely exerts its anticonvulsant action by affecting
      seizure spread and by raising seizure threshold. MDL 27,192 did not display any
      signs of tolerance following subchronic (15 day) administration. In tests of
      neuroprotective potential, MDL 27,192 reduced infarct volume in a permanent
      middle cerebral artery occlusion model of focal cerebral ischemia in rats and
      reduced the loss of hippocampal dentate hilar neurons in an animal model of
      unilateral head injury. In summary, MDL 27,192 possesses a broad-spectrum
      anticonvulsant profile. The potential for reduced tolerance and neuroprotective
      activity are additional positive features of MDL 27,192's preclinical profile.

PMID- 9169291
TI  - Differential effects mediated by GABAA receptors in thalamic nuclei in lh/lh
      model of absence seizures.
AB  - Absence seizures represent synchronized burst-firing of thalamocortical neurons,
      which are driven by tonic GABAergic output of nucleus reticularis thalami (NRT).
      Activation of GABAA receptors on NRT neurons reduces NRT output and retards
      thalamocortical burst-firing. Although this mechanism in NRT may underlie
      antiabsence effects of benzodiazepines, it does not explain observations that
      barbiturates can worsen absence-seizures. In this study we tested the hypothesis
      that clonazepam and phenobarbital produce differential effects on GABAA receptors
      in the lh/lh genetic model of absence seizures after microinjection into NRT
      compared to VLa, a prototypic relay nucleus containing thalamocortical neurons.
      In NRT, phenobarbital (16-1600 nmol/cannula), clonazepam (160-2200 pmol/cannula)
      and muscimol (8.8-263 pmol/cannula) significantly suppressed absence seizure
      frequency. In VLa, phenobarbital (1.6 nmol) and muscimol (0.88 pmol) increased
      seizure frequency, whereas higher doses (160 nmol and 88 pmol, respectively)
      significantly suppressed seizure frequency. In contrast, clonazepam produced no
      effect on seizure frequency even at a dose of 2.2 nmol; this same dose
      significantly suppressed absence seizures after microinjection into NRT. These
      findings suggest that activation of GABAA receptors in NRT may suppress absence
      seizures, and that phenobarbital may worsen absence seizures through actions on
      GABAA receptors in thalamocortical cells (VLa). Region-specific GABAA receptor
      isoforms may underlie the contrasting effects of clonazepam after microinjection
      into NRT and VLa.

PMID- 9169292
TI  - Is cell death necessary for hippocampal mossy fiber sprouting?
AB  - To examine the relationship between cell death and sprouting of the mossy fibers,
      repeated seizures of the hippocampal-parahippocampal circuit were elicited in
      anesthetized rats. The presence of mossy fiber growth was assessed with the
      Timm's stain for zinc. At 4 weeks, after 18 repeated seizures, there was a
      significant increase in the degree of zinc containing granules in the inner
      molecular layer of the dentate gyrus. The amount of sprouting was less than that
      seen four weeks after a single injection of kainic acid. A silver impregnation
      stain and an assay for damaged DNA were used to detect damaged or dying neurons
      and immunohistochemistry for a 72 kDa heat shock protein was used to detect any
      neurons that had suffered potentially injurious stress. The same number of
      repeated seizures that caused sprouting of the mossy fibers did not cause
      detectable cell death or severe stress in any cells within the hippocampus,
      subicular region or adjacent entorhinal cortex. These experiments demonstrate
      that repeated seizures of the hippocampal-parahippocampal circuits can cause
      sprouting of mossy fibers in the absence of evidence of cell death. This supports
      the hypothesis that alterations in intrinsic neural excitability and impulse
      activity from the dentate gyrus can result in growth of axonal processes in the
      adult rat brain.

PMID- 9169293
TI  - A calcium antagonistic effect of the new antiepileptic drug lamotrigine.
AB  - The new antiepileptic drug lamotrigine (LTG; 3,5-diamino-6-(2,3-dichlorophenyl)
      1,2,4-triazine) has been shown to be effective in the treatment of focal
      epilepsies with or without secondary generalization. Furthermore, some case
      reports indicate an efficacy in the treatment of bipolar affective disorders. It
      has been suggested that the main mechanism of action of LTG is the inhibition of
      glutamate release through blockade of voltage sensitive sodium channels and
      stabilisation of the neuronal membrane. Since some antidepressant drugs and the
      antiepileptic substance carbamazepine have calcium antagonistic properties, which
      may be of significance in the pathophysiology of epilepsies and affective
      disorders, the interaction of lamotrigine with carbamazepine and the organic
      calcium channel blocker verapamil was analyzed in the low Mg(2+)-induced model
      epilepsy which has been shown to be suppressed specifically by organic calcium
      antagonists. Lamotrigine reduced the frequency of occurrence of low-magnesium
      induced field potentials in CA1 and CA3 areas of the hippocampus slice
      preparation (guinea pigs) in a dose-dependent manner. The subthreshold
      concentrations which yielded no effect were 1 mumol/l for lamotrigine, 10 mumol/l
      for carbamazepine and 2 mumol/l for verapamil. Combinations of these subthreshold
      concentrations elicited a reduction in the repetition rate of field potentials.
      The results indicate that lamotrigine behaves additive with verapamil and
      carbamazepine what can be due to a common action on the same subtype of calcium
      channels. It can be assumed that lamotrigine may have besides its action on high
      frequency sodium dependent action potentials also effects on calcium channels.

PMID- 9169294
TI  - Atypical facial pain: a double-blind placebo-controlled crossover pilot study of
      subcutaneous sumatriptan.
AB  - A double-blind placebo-controlled crossover pilot study involving 19 patients was
      undertaken to evaluate the efficacy of subcutaneous sumatriptan, a selective 5
      hydroxytryptamine (5-HT)-like receptor agonist, in the treatment of atypical
      facial pain (AFP). A reduction in total pain was found 120 min post injection in
      the sumatriptan group. Most patients, however, described the medication as
      ineffective overall, despite significant pain score reduction. The temporary
      improvement of pain scores with the active drug was thought to be too small to be
      of any clinical benefit, but suggests that vascular or neurogenic mechanisms may
      be involved in the aetiology of AFP. Sumatriptan is not an appropriate
      therapeutic option for patients with AFP, but could prove a valuable drug in
      experimental clinical pharmacology.

PMID- 9169295
TI  - Biphasic effects of 8-OH-DPAT on endurance of treadmill performance in the male
      rat.
AB  - Administration of the 5-HT1A receptor agonist 8-OH-DPAT produced a biphasic
      pattern of effects on endurance performance of rats walking on top of a treadmill
      drum ([symbol: see text] = 166 mm, 16 rpm; approximately 8 m min-1), with
      enhanced performance at a low dose (0.1 mg kg-1 s.c.) followed by impairment (0.2
      0.8 mg kg-1). The partial 5-HT1A receptor agonist (-)-pindolol improved the
      performance in the low dose range (0.5-2.0 mg kg-1 s.c.), whereas a higher dose
      (8 mg kg-1) was ineffective. The 5-HT1A receptor antagonist WAY-100,635 produced
      an impaired performance at a low dose (12.5 micrograms kg-1 s.c.), with a
      recovery of performance at higher doses (50-200 micrograms kg-1). It is suggested
      that the inhibition of central serotonergic neurotransmission produced by
      stimulation or blockade of 5-HT1A auto- and post-synaptic receptors,
      respectively, results in an improved endurance performance on the treadmill,
      whereas stimulation of postsynaptic 5-HT1A receptors has the opposite action. In
      support of this contention, the impaired performance produced by a high dose of 8
      OH-DPAT (0.8 mg kg-1) was antagonized by pretreatment with (-)-pindolol (2 mg kg
      1 s.c.).

PMID- 9169296
TI  - The effect of chronic lithium treatment on the calibre of axons and nerve fibres
      in the rat sural nerve.
AB  - Cases of peripheral neuropathy have been reported in humans receiving lithium
      therapy. However, no previous studies have addressed the question of whether
      chronic lithium treatment causes morphological changes in the peripheral nervous
      system in experimental animals. The present study used stereological methods to
      determine whether long-term administration of lithium affected the calibre of the
      axons or of the nerve fibres in the rat sural nerve. Twenty-two rats were divided
      into 2 groups and given either no treatment or lithium, with serum levels
      averaging from 0.5 to 0.7 mmol/l. After 30 weeks of treatment, the animals were
      killed and the sural nerve was isolated at the level of the knee and was removed.
      The cross-sectional area of axons and of nerve fibres was estimated by point
      counting. Compared with the controls, a strong tendency towards a reduced nerve
      fibre area in the lithium-treated animals was found, with a between-group
      difference of 1.79 microns 2 (P = 0.06). For the axon area, the difference was
      0.73 micron 2 (P = 0.20).

PMID- 9169297
TI  - Differential effects of three 5-HT receptor antagonists on the performance of
      rats in attentional and working memory tasks.
AB  - The effects of three different serotonin (5-HT) receptor antagonists (ketanserin,
      methysegide, methiothepin) in the modulation of attention, working memory and
      behavioural activity were investigated in this study by assessing the performance
      of rats in two separate cognitive models; the 5-choice serial reaction time (5
      CSRT) task, which measures attention, and the delayed non-matching to position
      (DNMTP) task, which measures working memory. Methysergide and methiothepin bind
      at the 5-HT1 and 5-HT2 as well as the 5-HT5-7 receptors, with varying degrees of
      selectivity, and ketanserin binds at the 5-HT2A receptors rather selectively.
      None of these agents bind to any significant extent to 5-HT3 or 5-HT4 receptors.
      In the 5-CSRT task, neither methiothepin (0.15 mg/kg) nor ketanserin (1.0 and 3.0
      mg/kg) impaired the choice accuracy of rats, although they induced sedation. The
      low doses of methysergide (1.5 and 3.0 mg/kg) slightly increased the behavioural
      activity of rats, whereas the high dose of methysergide (15.0 mg/kg) reduced
      behavioural activity and slightly reduced choice accuracy of the rats in the
      attentional task (monitoring of visual stimuli) under the baseline conditions or
      curtailed stimulus duration. This effect was not augmented at the reduced
      stimulus intensity. These findings suggest that the high dose of methysergide did
      not interfere with the visual discrimination of rats. Furthermore, methysergide
      did not reduce motivation for this task, since it did not increase food
      collection latencies. In the DNMTP task, methiothepin (0.15 mg/kg) induced a
      delay non-dependent deficit in choice accuracy. This could be due to an impaired
      alternation ability or akinesia, which increases an actual delay between sample
      and choice. Methiothepin (0.15 mg/kg) also interfered with behavioural activity
      of rats. Interestingly, ketanserin (1.0 mg/kg and 3.0 mg/kg) and methysergide
      (3.0-15.0 mg/kg) neither impaired the choice accuracy nor reduced the behavioural
      activity of rats in the DNMTP task. These results suggest that the blockade of 5
      HT2A receptors does not interfere with attention and working memory per se.
      However, all three serotonin receptor antagonists interfered with behavioural
      activity of rats in the 5-CSRT task more severely than in the DNMTP task. The
      possible role of serotonin and non-serotonin receptors underlying the influence
      of these antagonists on behavioural activity will be discussed.

PMID- 9169298
TI  - The effects of the 5-HT1A agonist flesinoxan, in three paradigms for assessing
      antidepressant potential in the rat.
AB  - 5-HT1A receptor agonists have been shown to be effective clinically in the
      treatment of depression and anxiety. Flesinoxan is an example which is highly
      selective for the 5-HT1A receptor subtype. The objective of this study was to
      appraise the antidepressant potential of flesinoxan (1 and 3 mg/kg s.c.) in three
      tests which are indicative of antidepressant activity. These are (1) the forced
      swim test, following sub-acute administration, (2) 'open field' activity in the
      olfactory bulbectomised (OB) rat, following chronic administration, and (3) 8-OH
      DPAT-induced hypothemia following chronic treatment. Both doses of flesinoxan
      significantly reduced the immobility time in the sham and OB groups when compared
      to their respective controls. In the 'open field', there was a significant
      increase in the ambulation of the OB control group. The higher dose of flesinoxan
      significantly reduced this deficit. In addition both doses of flesinoxan
      significantly attenuated the 8-OH-DPAT-induced hypothermic response. These
      effects of flesinoxan are quantitatively similar to those seen following the
      chronic administration of antidepressants. These studies illustrate the potential
      antidepressant properties of flesinoxan, and hence further emphasise the role of
      the 5-HT1A receptor in the pathogenesis of depression.

PMID- 9169299
TI  - Pharmacological treatment of severely depressed patients: a meta-analysis
      comparing efficacy of mirtazapine and amitriptyline.
AB  - Efficacy data were available from 405 severely depressed patients (baseline 17
      item Hamilton Rating Scale for Depression-HAMD scores > or = 25) participating in
      randomized, double-blind, amitriptyline-controlled studies of mirtazapine. Main
      efficacy variable were changes from baseline in the group mean 17-item HAMD
      scores and responder rates. Secondary efficacy variables were changes in
      depressed mood item on the HAMD and in factors derived from the 17-item HAMD
      scale. Treatment with either mirtazapine or amitriptyline resulted in robust
      reductions of baseline HAMD scores and in similar and high percentages of
      responders. Both drugs produced favourable effects on depressed mood and on
      symptoms commonly associated with depression, such as anxiety, sleep and
      vegetative disturbances. There were neither statistically significant nor
      clinically relevant differences between mirtazapine and amitriptyline at any
      assessment point nor at endpoint. The results demonstrate that the new
      antidepressant mirtazapine and the tricyclic antidepressant amitriptyline are
      equally effective in the treatment of severely depressed patients.

PMID- 9169300
TI  - Olanzapine versus haloperidol: acute phase results of the international double
      blind olanzapine trial.
AB  - A 6-week acute phase of an international 1-year double-blind study was conducted
      comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day,
      and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a
      dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with
      schizophrenia. The purpose was to determine whether olanzapine demonstrated a
      dose-related ability to decrease overall psychopathology with minimal associated
      extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine
      group showed statistically significantly greater improvement in overall
      psychopathology based on mean change in the CGI Severity score and statistically
      significantly greater improvement in positive psychotic symptoms based on mean
      change in both the BPRS positive score and the PANSS positive score compared with
      the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose
      response curve was observed across the range of all olanzapine dose groups. Acute
      extrapyramidal syndromes were reported less frequently among all olanzapine
      groups compared with the haloperidol group. Endpoint mean change on both the
      Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all
      olanzapine treatment groups compared with worsening for the haloperidol group.
      Olanzapine was associated with weight gain but did not appear to have any
      clinically meaningful effect on vital signs. Although olanzapine was associated
      with some increase in prolactin concentrations, increases were transient,
      occurred less often, and were of lesser magnitude than those observed with
      haloperidol.

PMID- 9169301
TI  - Implication of beta 1- and beta 2-adrenergic receptors in the antinociceptive
      effect of tricyclic antidepressants.
AB  - Tricyclic antidepressants have been shown to be useful for the treatment of pain
      of varying etiology. Monoaminergic systems seem to be implicated in this
      phenomenon. In this study, the influence of the selective beta 1- (CGP 20712A)
      and beta 2- (ICI 118551) adrenergic blockers on the antinociceptive effect of
      desipramine and nortriptyline was studied in mice using physical and chemical
      nociceptive tests that implicate different levels of sensory-motor integration in
      the central nervous system (CNS). An activity test was performed to detect "false
      positive" or "false negative" results. Results obtained show that both CGP 20712A
      and ICI 118551 are able to antagonize the antinociceptive effect of these
      antidepressants in physical tests (hot-plate and tail-flick). However, in
      chemical tests (acetic acid and formalin), the analgesic effect of the
      antidepressants used was only antagonized by CGP 20712A. These results suggest
      that the analgesic effect of desipramine and nortriptyline is mediated by beta
      adrenoceptors. The beta-adrenoceptor involved depends on the type of nociceptive
      stimulus: beta 1 and beta 2 are both implicated when the stimulus is physical,
      but only beta 1 is involved when the stimulus is chemical.

PMID- 9169302
TI  - Controlled trials of inositol in psychiatry.
AB  - Inositol is a simple polyol precursor in a second messenger system important in
      the brain. Cerebrospinal fluid inositol has been reported as decreased in
      depression. A double-blind controlled trial of 12 g daily of inositol in 28
      depressed patients for four weeks was performed. Significant overall benefit for
      inositol compared to placebo was found at week 4 on the Hamilton Depression
      Scale. No changes were noted in hematology, kidney or liver function. Since many
      antidepressants are effective in panic disorder, twenty-one patients with panic
      disorder with or without agoraphobia completed a double-blind, placebo
      controlled, four week, random-assignment crossover treatment trial of inositol 12
      g per day. Frequency and severity of panic attacks and severity of agoraphobia
      declined significantly with inositol compared to placebo. Side-effects were
      minimal. Since serotonin re-uptake inhibitors benefit obsessive compulsive
      disorder (OCD) and inositol is reported to reverse desensitization of serotonin
      receptors, thirteen patients with OCD completed a double-blind controlled
      crossover trial of 18 g inositol or placebo for six weeks each. Inositol
      significantly reduced scores of OCD symptoms compared with placebo. A controlled
      double-blind crossover trial of 12 g daily of inositol for a month in twelve
      anergic schizophrenic patients, did not show any beneficial effects. A double
      blind controlled crossover trial of 6 g of inositol daily vs. glucose for one
      month each was carried out in eleven Alzheimer patients, with on clearly
      significant therapeutic effects. Antidepressant drugs have been reported to
      improve attention deficit disorder (ADDH) with hyperactivity symptomatology. We
      studied oral inositol in children with ADDH in a double-blind, crossover, placebo
      controlled manner. Eleven children, mean age 8.9 +/- 3.6 years were enrolled in
      an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight.
      Results show a trend for aggravation of the syndrome with myo-inositol as
      compared to placebo. Recent studies suggest that serotonin re-uptake inhibitors
      are helpful in at least some symptoms of autism. However a controlled double
      blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine
      children with autism. Cholinergic agonists have been reported to ameliorate
      electroconvulsive therapy (ECT)-induced memory impairment. Inositol metabolism is
      involved in the second messenger system for several muscarinic cholinergic
      receptors. Inositol 6 g daily was given in a crossover-double-blind manner for
      five days before the fifth or sixth ECT to a series of twelve patients, without
      effect. These results suggest that inositol has therapeutic effects in the
      spectrum of illness responsive to serotonin selective re-uptake inhibitors,
      including depression, panic and OCD, and is not beneficial in schizophrenia,
      Alzheimer's ADDH, autism or ECT-induced cognitive impairment.

PMID- 9169304
TI  - Melperone treatment in an organic delusional syndrome induced by
      hyperprolactinemia: a case report.
AB  - A young female with organic delusional syndrome induced by hyperprolactinemia was
      admitted to the Psychiatry Clinic of Ankara Social Security Hospital. The most
      striking characteristic of her history was either worsening of the endocrinologic
      clinical outcome under conventional neuroleptic treatment or worsening of
      clinical psychiatric outcome under bromocriptine therapy. A new atypical
      neuroleptic, melperone, suggested to minimally affect plasma prolactin levels,
      was started. Her psychotic complaints significantly subsided and she was devoid
      of any symptomatological change regarding her endocrinological status. These
      results were discussed.

PMID- 9169303
TI  - Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral
      melatonin: a case report.
AB  - A 43 year old woman had suffered from insomnia for the past 11 years and was
      being treated with benzodiazepines. All attempts to stop benzodiazepine treatment
      resulted in withdrawal symptoms and a renewal of the insomnia. Treatment with 1
      mg of controlled release melatonin enabled the patient to completely cease any
      benzodiazepine use within two days, with an improvement in sleep quality and no
      side effects. Examination of urinary 6-sulphatoxymelatonin levels before the
      melatonin treatment indicated that the levels were very low and lacked the
      typical circadian rhythm of excretion. Reexamination of 6-sulphatoxymelatonin
      levels during melatonin treatment revealed the existence of a normal circadian
      rhythm of excretion. This case may suggest that some of the people suffering from
      insomnia and addicted to benzodiazepines may successfully undergo withdrawal from
      these drugs and improve their sleep by means of treatment with melatonin. The
      results of this single case study warrant further investigation of a larger
      population by means of a double-blind placebo-drug study.

PMID- 9169305
TI  - Is there a role for a pure noradrenergic drug in the treatment of depression?
AB  - Depression is thought to result from a dysfunction in the noradrenergic or
      serotonergic systems. The noradrenergic system appears to be associated with
      increased drive, whereas the serotonergic system relates more to changes in mood
      and it is possible that the different symptoms of depression may benefit from
      drugs acting mainly on one or other of the neurotransmitter systems. A series of
      studies has shown that interruption of serotonin synthesis compromises the
      efficacy of serotonin but not noradrenaline reuptake inhibitors, and interruption
      of noradrenaline synthesis compromises the efficacy of noradrenaline but not
      serotonin reuptake inhibitors (SSRIs). This suggests that the two classes of
      drugs owe their activity to functional changes in different neurotransmitter
      systems. Reboxetine represents a new class of drugs-the selective noradrenaline
      reuptake inhibitors (NARIs). It acts specifically at noradrenergic sites unlike
      the non-selective tricyclic antidepressants (TCAs). NARIs have a role in the
      treatment of depression, either alone or as adjunctive therapy.

PMID- 9169306
TI  - Noradrenaline in basic models of depression.
AB  - This review reports anatomical studies evaluating central and peripheral alpha 2-
      and beta-adrenoceptors. The results suggest abnormalities exist in the
      noradrenergic system in depressed patients. Most animal models involve the use of
      stress to simulate depression in man. All models that have been developed lead to
      differential changes in noradrenergic function. We have assessed the effects of
      reboxetine, a novel, selective noradrenaline-reuptake inhibitor (NARI) in
      olfactory bulbectomised rats, a procedure that induces significant changes in
      amygdala function. Reboxetine is an effective antidepressant in the forced swim
      test and open field test in bulbectomised rats. Unlike the tricyclic
      antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs),
      reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that
      reboxetine is selective for the noradrenergic system. Owing to the abnormalities
      that occur in depression, it would seem sensible to target the noradrenergic
      system for treatment of this condition.

PMID- 9169307
TI  - The effects of antidepressants on psychomotor function with particular reference
      to reboxetine.
AB  - This review assesses the relative efficacy and side-effect profile of the
      currently available treatment options for major depression and the new selective
      noradrenergic agent, reboxetine. The effects of these treatments on psychomotor
      function are reviewed using: choice reaction time (CRT) and critical flicker
      fusion threshold (CFFT) measurements to compare and contrast the various
      antidepressants. Tricyclic antidepressant (TCA) agents are associated with an
      increased risk of accidents, especially in the elderly (primarily accidents
      related to driving or falls/fractures due to postural hypotension). In
      comparison, the newer noradrenergic agents such as reboxetine have demonstrated
      significant improvements in the incidence and severity of effects on psychomotor
      function. Such a lack of side-effects makes agents like reboxetine most useful
      for the treatment of depression in ambulant patients performing their usual
      activities of daily living.

PMID- 9169308
TI  - Review of the pharmacokinetics and metabolism of reboxetine, a selective
      noradrenaline reuptake inhibitor.
AB  - The pharmacokinetics and metabolism of reboxetine, a selective noradrenaline
      reuptake inhibitor, in humans and animal models are reviewed here. Reboxetine has
      potent antidepressant activity, low affinity for alpha-adrenergic and muscarinic
      receptors and low toxicity in animals. It is a mixture of (R,R) and (S,S)
      enantiomer, the latter being more potent but no qualitative differences in
      pharmacodynamic properties are observed between the two. Humans rapidly absorb
      reboxetine (tmax about 2 h) with a terminal half-life of elimination (t1/2) of 13
      h, allowing twice-daily administration. Animal models also rapidly absorb
      reboxetine (tmax 0.5-2 h) but t1/2 was 1-2 h. Food does not affect
      bioavailability. There were no major inter-species differences in the metabolic
      profile of reboxetine. Elimination is principally renal in humans and monkeys.
      Reboxetine has linear pharmacokinetics in young, healthy males for single doses
      of 1-5 mg and in elderly, female depressed patients (up to 4 mg b.i.d.). Multiple
      dosing, gender or liver insufficiency had no significant effects on the
      pharmacokinetics. Elderly (particularly frail elderly) patients and patients with
      severe renal impairment may need dose reduction. Reboxetine shows no clinically
      relevant interaction with lorazepam and has no inhibitory effects on the major
      enzymes involved in drug metabolism. It may be possible to use reboxetine in
      combination with monoamine oxidase inhibitors as it has no inhibitory effect on
      this enzyme; in addition, it may protect patients against tyramine-induced
      reactions. In conclusion, reboxetine seems to be an antidepressant with
      negligible interference with the pharmacokinetics of other drugs thus fewer drug
      drug interactions are expected.

PMID- 9169309
TI  - Efficacy and tolerability of reboxetine compared with imipramine in a double
      blind study in patients suffering from major depressive offsodes.
AB  - A 6-week, randomised, double-blind, multicentre study in 256 patients with a DSM
      III-R diagnosis of major depression was carried out to compare the selective
      noradrenaline reuptake inhibitor (NARI), reboxetine, with the reference standard
      tricyclic antidepressant, imipramine. The efficacy of reboxetine, as measured by
      the extent of improvement of Hamilton Depression Rating Scale. Montgomery and
      Asberg Depression Rating Scale and the Clinical Global Impression Scale, was
      similar to that of imipramine. The improvement was observed in the overall
      population and in severely depressed and melancholic patients. Reboxetine
      tolerability compared favourably with that of imipramine. Frequency of
      discontinuation due to adverse events was lower in the reboxetine-treated group
      (10.0%) than in the imipramine-treated group (14.3%), and the cumulative risk of
      development (Kaplan-Meier analysis) of dry mouth, hypotension and/or related
      symptoms and tremor was significantly higher on imipramine than on reboxetine.

PMID- 9169310
TI  - Do noradrenaline and serotonin differentially affect social motivation and
      behaviour?
AB  - In a placebo-controlled 8-week study comparing the selective noradrenaline re
      uptake inhibitor (NARI), reboxetine, with the selective serotonin reuptake
      inhibitor (SSRI), fluoxetine, in major depression, patient social motivation and
      behaviour were investigated through a newly developed 21-item self-rating scale,
      the Social Adaptation Self-evaluation Scale (SASS). At last assessment the mean
      SASS total score was significantly superior on both reboxetine (n = 103) and
      fluoxetine (n = 100) compared with on placebo (n = 99). In addition, the SASS
      total score in the reboxetine group was significantly higher compared with the
      fluoxetine group. At point-biserial correlation analysis, all but one item
      discriminated reboxetine from placebo, while only 12 items discriminated
      fluoxetine from placebo. In the reboxetine-fluoxetine comparison, nine items
      showed a positive association with reboxetine, while the opposite was never seen;
      the association was maximal in the area of negative self perception and lack of
      motivation towards action. These results support, at social functioning level, a
      differential effect of selective manipulation of the noradrenergic or
      serotonergic system in keeping with the long-debated hypothesis on the specific
      involvement of serotonin in regulating mood and of noradrenaline in sustaining
      drive.

PMID- 9169311
TI  - Development and validation of a social functioning scale, the Social Adaptation
      Self-evaluation Scale.
AB  - The Social Adaptation Self-evaluation Scale (SASS) is a 21-item newly developed
      scale for the evaluation of patient social motivation and behaviour in
      depression. The scale was submitted to a validation procedure based on the data
      from a general population survey in 4000 individuals and from two controlled
      studies comparing the new selective noradrenaline reuptake inhibitor (NARI),
      reboxetine, with placebo and/or fluoxetine in 549 patients with major depression.
      The scale was shown to be valid, reliable and sensitive to change. The results of
      the multivariate analyses allowed the identification of three principal factors
      and five clusters. In view of its simplicity of use, and of its peculiar
      characteristic of investigating patient perspective on self and environment
      perception and on social motivation and behaviour, the scale represents a useful
      additional tool for the evaluation of social functioning in depression and will
      facilitate the development of new antidepressants with differential effects in
      this domain in depressed patients.

PMID- 9169312
TI  - Perceiving wisdom: do age and gender play a part?
AB  - The wisdom perceived to be possessed by videotaped individuals of varying ages
      was evaluated using the Smith and Baltes definition of wisdom [1]. The Life
      Planning Tasks (work-family dilemmas) and corresponding think-aloud protocols
      (responses) developed by Smith and Baltes were transformed into videotape stimuli
      to assess the presence of wisdom. Using an instrument derived from the Smith and
      Baltes description of wisdom, undergraduate respondents evaluated the wisdom they
      perceived to be contained in videotaped responses to Life-Planning Tasks. The age
      of the Life-Planning Task respondent was manipulated as either older or younger.
      A significant interaction between the age and gender of the videotape respondents
      and an interpretation of its effect on the perception of wisdom is discussed.
      Correlational results reveal a positive relationship between the lay person's
      definition of wisdom and that which was derived from Smith and Baltes.

PMID- 9169313
TI  - Achievement domain and life expectancies in Japanese civilization.
AB  - Previous studies have found that the expected life span of eminent personalities
      may vary systematically according to the domain of achievement. The current
      investigation examines this phenomenon more closely by 1) introducing
      methodological controls for potential gender and cohort artifacts, 2) adding
      substantive predictors (e.g., suicide and homicide) that provide clues regarding
      the substantive basis for the differences, 3) scrutinizing a greater variety of
      achievement domains in both creativity and leadership, and 4) using a non-Western
      sample of historical figures (1,632 Japanese born between 450 and 1883 A.D.).
      Multiple regression analyses revealed domain contrasts in life expectancy (e.g.,
      the shorter life spans of fiction authors and political figures, but the longer
      life spans of religious leaders and sword makers). In addition, the analyses
      helped decipher the extent to which these domain differences were due to violent
      death or to the stress of occupying high positions of power.

PMID- 9169314
TI  - Cultural differences in caregiving motivations for demented parents: Korean
      caregivers versus American caregivers.
AB  - The study examined differences in motivations for parent care of Korean
      caregivers and Caucasian American caregivers of elderly parents with dementia. A
      number of American caregivers, mostly daughters of the demented parents, had
      affectionate relationships with their parents, but they expressed a relatively
      low degree of filial responsibility. In contrast, among Korean caregivers, the
      care of demented parents was predominantly the responsibility of daughters-in-law
      who were less likely to have affectionate relationships with the parents-in-law.
      However, Korean caregivers expressed a significantly higher level of filial
      responsibility than the American caregivers. Some cultural differences between
      the two ethnic groups associated with parent care were discussed.

PMID- 9169315
TI  - Evaluation of infantilizing speech in a rehabilitation setting: relation to age.
AB  - The purpose of the present study was to assess whether reactions to infantilizing
      speech and content are a function of age when levels of dependence within an
      institutional environment are controlled. Ten individuals below the age of sixty
      five were compared with ten above age sixty-five. Respondents were given two sets
      of materials designed to produce comparative ratings of adult and infantilized
      speech content and intonation. The over sixty-five age group did not detect a
      difference between adult and infantilizing content. The under sixty-five age
      group reacted more negatively to infantilizing content than did the older group.
      Independence scores were not significantly correlated with either set of speech
      ratings, or to age. The difference between older and younger adults with the same
      level of functional impairment supports the empirical literature that
      infantilization is due in part to stereotyped expectations regarding the aged as
      more dependent and hence in need of childlike treatment.

PMID- 9169316
TI  - The Reminiscence Functions Scale: a replication.
AB  - This article reports the findings of a replication and validation study of the
      factor structure of the recently developed Reminiscence Functions Scale (RFS)
      [1]. Three hundred and ninety-nine adult subjects ranging in age from seventeen
      to forty-five years (M age = 22.7, SD = 5.7) completed the RFS. A principal
      components analysis indicated the viability of an eight-factor scale which
      strongly parallels the earlier scale construction. Factors were labeled: Boredom
      Reduction, Death Preparation, Identity, Problem-Solving, Conversation, Intimacy
      Maintenance, Bitterness Revival, and Teach/Inform. Internal consistency scores
      ranged from .74 to .86 and closely duplicated original scores. Age differences on
      Death Preparation and Teach/Inform were replicated. Potential uses of the RFS are
      documented.

PMID- 9169317
TI  - Strengths and needs of working-class African-American and Anglo-American
      grandparents.
AB  - This study examined gender and racial differences in the grandparenting strengths
      and needs of working class grandparents. A total of 192 African-American and
      Anglo-American grandmothers and grandfathers from the Washington, D.C.
      metropolitan area were administered the Grandparent Strengths and Needs
      Inventory. Grandmothers perceived themselves to be significantly more involved in
      teaching their grandchildren and significantly more successful in the grandparent
      role than grandfathers. African-American grandparents perceived themselves to be
      significantly more involved in teaching their grandchildren than Anglo-American
      grandparents, but were also significantly more likely than their Anglo-American
      counterparts to express frustration and need for information about the
      grandparenting role. A significantly greater percentage of African-American
      grandparents expressed interest in taking a grandparent education course than
      Anglo-American grandparents. Implications of the findings for grandparent
      education are discussed.

PMID- 9169318
TI  - Arsenic and the skin.

PMID- 9169319
TI  - Dermatologic manifestations of hepatitis C infection.

PMID- 9169320
TI  - Psoriasis and calcipotriol: an overview.

PMID- 9169321
TI  - Psoriasis and sex: a study of moderately to severely affected patients.
AB  - BACKGROUND: Psoriasis can have a significant impact upon sexual functioning for
      30%-70% of patients. We examined the dermatologic and psychologic factors
      associated with the effect of psoriasis on this important dimension of quality of
      life. METHODS: One hundred and twenty consenting psoriasis patients (63 men and
      57 women; mean +/- SD age, 46.8 +/- 15.7 years; mean +/- SD total body surface
      area affected, 53.4% +/- 22.9%) completed a battery of questionnaires which
      included their response (endorsed with a "Yes" or "No") to the following
      question: "Do you believe that since the onset of psoriasis your sexual activity
      has declined?" The differences in dermatologic and psychologic measures between
      the subgroup that endorsed a "Yes" response and the subgroup that endorsed a "No"
      response were examined. RESULTS: Forty-nine out of 120 patients (40.8%) were
      sexually affected, i.e. they endorsed a "Yes." There were no significant
      differences between the affected and unaffected groups with respect to marital
      status, age, sex, and duration of psoriasis. The affected group reported more
      joint pains (P = 0.01), marginally greater psoriasis severity affecting the groin
      region (P = 0.07), greater scaling (P = 0.06), and greater pruritus severity (P =
      0.07). Psychologically, the affected group had higher depression scores (P =
      0.02) which were in the range for clinical depression, a greater tendency (P =
      0.02) to seek the approval of others, and a marginally greater tendency (P =
      0.08) to drink alcohol. A decline in sexual activity was related to a decrease in
      the patient's sex drive for 42.6% of patients; however, only 14.9% of these
      patients attributed the decline in their sexual activity to decreased sex drive
      of their spouse/partner. CONCLUSION: In addition to some dermatologic factors,
      comorbid psychologic factors, such as depression and a tendency for alcohol use,
      may be important determinants of decreased sexual functioning in psoriasis.

PMID- 9169322
TI  - Intradermal antigen tests and the Koebner phenomenon in psoriasis.
AB  - BACKGROUND: Psoriasis is one of several dermatologic conditions in which
      nonspecific irritation may elicit the disease where it was not previously
      present. In this study we aimed to assess the cutaneous cellular immune reaction
      with intradermal antigen tests and the relation between Koebner's phenomenon and
      intradermal antigens. METHODS: Thirty psoriasis patients and 20 control subjects
      were tested with 0.1 mL intradermal injections of purified protein derivative
      (PPD), Candida (C), mumps (M), mixed respiratory vaccine (MRV), and saline
      control solutions. Koebner status was also determined in the psoriatic patients.
      Injection sites were evaluated at 72 h and on the eighth, 12th, 16th, and 20th
      days for erythema, induration, and local development of psoriasis. RESULTS: Two
      patients were Koebner positive and developed psoriasis at all five injection
      sites. However, local psoriasis development was observed at one or more injection
      sites in five Koebner-negative patients. In addition, intensity of delayed
      hypersensitivity reaction and resolution times demonstrate no significant
      difference between psoriatic and nonpsoriatic subjects statistically (P > 0.05).
      CONCLUSIONS: These findings may indicate that intradermal antigens used in this
      study were more effective in inducing the Koebner phenomenon than injury alone.
      Furthermore, we observed that there is no meaningful difference between psoriatic
      and nonpsoriatic subjects in developing cutaneous cellular immune reactions.

PMID- 9169324
TI  - Cutaneous localization of endothelin-1 in patients with systemic sclerosis:
      immunoelectron microscopic study.
AB  - BACKGROUND: Endothelin-1 (ET-1) has some relation to the pathogenesis of systemic
      sclerosis (SSc) and Raynaud's phenomenon. This study was performed to determine
      the localization of ET-1 in patients with SSc. METHODS: The localization of ET-1
      on the specimen by skin biopsies from nine patients with SSc, was observed with
      immunoelectron microscopic techniques. RESULTS: High-density deposits existed on
      the ribosomes and on the rough endoplasmic reticulum in the endothelial cells of
      microvessels of the upper dermis. The same findings were also seen in the
      fibroblasts of the dermis, but not found in the skin of normal controls. The
      level of deposits in the endothelial cells and dermal fibroblasts seemed to have
      a positive correlation with the serum levels of ET-1 of patients with SSc.
      CONCLUSIONS: From these results, it can be seen that ET-1 is produced much more
      from the endothelial cells and fibroblasts of the dermis in the skin of SSc
      patients than from the normal controls. It is suspected that ET-1 is one of the
      pathogenetic factors of SSc.

PMID- 9169323
TI  - The profile and outcome of pustular psoriasis in Singapore: a report of 28 cases.
AB  - BACKGROUND: Pustular psoriasis is a rare form of psoriasis that can be divided
      into generalized and localized forms. The aim of this study is to describe the
      patient profile and outcome of pustular psoriasis seen at a tertiary referral
      skin center in a tropical country. METHODS: The records of all patients with
      pustular psoriasis during the 4 years from 1989 to 1993 were reviewed. Diagnostic
      criteria for selection included at least one episode of either generalized or
      localized macroscopic noninfective pustulation. RESULTS: There were 28 patients
      with pustular psoriasis, with an age range of 4-77 years. Nineteen patients had
      generalized pustular psoriasis: Von Zumbusch (seven), annular form (two),
      juvenile form (six), pustular psoriasis of pregnancy (one), and the localized
      form of generalized pustular psoriasis (three). Nine patients had localized
      pustular psoriasis: palmoplantar pustulosis (five) and acrodermatitis continua
      (four). Patients with the acute Von Zumbusch pattern had recalcitrant disease
      with multiple flares and significant morbidity and mortality. Patients with the
      annular form had a subacute onset and a chronic course. In patients with the
      juvenile form of generalized pustular psoriasis, two patterns could be
      recognized: Zumbusch form (four) and annular form (two). Despite significant
      morbidity, each of our young patients had a relatively benign course with no
      deaths and an excellent response to etretinate therapy. Our nine patients with
      localized pustular psoriasis all had a chronic course: the average duration of
      disease was 6 years for patients with palmoplantar pustulosis and 12 years for
      patients with acrodermatitis continua. CONCLUSIONS: The pattern of pustular
      psoriasis seen in Singapore is similar to that reported in the Western
      literature. Using these categories we can provide guidelines for treatment and
      prognosis.

PMID- 9169325
TI  - Tungiasis in New York.

PMID- 9169326
TI  - A case of systemic nodular panniculitis associated with M1 (Val213) Z phenotype
      of alpha 1-protease inhibitor.

PMID- 9169327
TI  - Complete resolution of psoriasis vulgaris after excision of thyroid cancer.

PMID- 9169328
TI  - Conjunctival involvement in familial chronic benign pemphigus (Hailey-Hailey
      disease).

PMID- 9169329
TI  - Co-existence of cutaneous and presumptive pulmonary alternariosis.

PMID- 9169330
TI  - Wells' syndrome: vesiculobullous presentation and possible role of ectoparasites.

PMID- 9169331
TI  - Pustular panniculitis in a patient with rheumatoid arthritis.

PMID- 9169332
TI  - Isolated cutaneous Mycobacterium avium complex infection in AIDS.

PMID- 9169333
TI  - Candida folliculitis mimicking tinea barbae.

PMID- 9169334
TI  - Localized cutaneous infection by Scedosporium prolificans (inflatum).

PMID- 9169335
TI  - Membranous lipodystrophy associated with insulin lipoatrophy.

PMID- 9169336
TI  - Topical calcipotriene in combination with UVB phototherapy for psoriasis.
AB  - A total of 20 patients with symmetric plaque-type psoriasis were recruited for a
      controlled, investigator-blinded, right-left study. None of the patients had used
      any therapy other than emollients for 2 months prior to starting in the trial.
      All patients had a negative antinuclear antibody. By history, all patients had
      previously improved upon exposure to sunlight or ultraviolet light. Two
      symmetrical sites of equal severity were selected as target areas. Each patient
      was treated on one side with mineral oil twice daily and on the opposite side
      with calcipotriene 0.005% ointment twice daily. The investigator was blinded as
      to which site received which topical treatment. Both sides were treated with
      equal doses of ultraviolet B (UVB) three times weekly in graduated
      suberythemogenic doses. Ultraviolet B radiation was emitted by a group of 6-ft
      fluorescent bulbs (Light Sources FS72 T12 UVB HO) in a standard phototherapy
      unit. The above regimen was continued for a total of 12 weeks. The severity of
      psoriasis in the target sites was rated by the examiner at baseline and at weekly
      intervals for the 12 weeks of study. Target sites were rated by severity of
      erythema, scaling, plaque elevation, and pruritus, with each of these parameters
      being assigned a score on a four-point scale: 0, clear; 1, mild; 2, moderate; 3,
      severe. The four scores were added together to arrive at a total severity score
      for each of the target sites. Statistical analysis was performed using the paired
      t test, P values less than 0.05 were considered statistically significant. Eleven
      of the 20 patients (55%) showed a greater decrease in the severity of their
      psoriasis with UVB plus calcipotriene compared with UVB plus mineral oil. The
      difference in severity scores between the two groups was statistically
      significant as early as week 1 (P < 0.05). The difference between the UVB and
      calcipotriene group versus the UVB and mineral oil group peaked between weeks 3
      and 6. The differences then decreased but remained statistically significant
      through to week 12 (Fig. 1). There were no instances of local cutaneous
      irritation, but mild photosensitivity occurred symmetrically on both sides in
      three patients.

PMID- 9169337
TI  - Demographic evaluation of successful antipsoriatic climatotherapy at the Dead Sea
      (Israel) DMZ Clinic.
AB  - BACKGROUND: Natural balneologic properties, thermomineral springs and unequivocal
      success in improving psoriasis, attract an ever-growing number of psoriatics to
      the DMZ Clinic on the shores of the Dead Sea in Israel. METHODS: This paper
      analyses the rate of success of this balneotherapy in 740 psoriatics who flew in
      from Germany specifically for this treatment, during 1995, as a function of sex,
      family history of the disease, number of previous treatments at the Dead Sea,
      skin type, skin involvement, joint involvement, duration of treatment, sun
      exposure schedule, remission length, and psychologic supervision. RESULTS: After
      4 weeks, 70% of the patients were completely cleared, this improvement being
      about the same across both sexes. Family history of the disease, skin type, and
      psychologic support did not affect the rate of success. On the other hand,
      previous treatments at the Dead Sea, moderate to severe skin surface involvement,
      and participation of arthritis, improved the chance of better clearing of the
      psoriatic condition. Similar improvement was obtained by a longer sun-exposure
      schedule and a complete-4-week treatment. CONCLUSION: These results indicate that
      the medical improvement in the psoriatic condition after a 4-week stay at the
      Dead Sea can be better enhanced and its remission prolonged if additional
      demographic and anamnestic factors are carefully taken into account.

PMID- 9169338
TI  - Coal tar therapy in palmoplantar psoriasis: old wine in an old bottle?
AB  - BACKGROUND: Palmoplantar psoriasis (PPP) is a disabling condition which is
      usually resistant to most of the available therapeutic modalities. Coal tar is an
      accepted therapy for psoriasis which has not been well studied for PPP. METHODS:
      Thirty patients with a plaque type of PPP were allocated into two groups: Group A
      (19 patients) were treated with 6% crude coal tar (CCT) ointment and Group B (11
      patients) were treated with white petrolatum and salicylic acid. In both groups,
      ointment was applied and left on overnight. Wearing of gloves and socks during
      the night and application of emollients in the day was routinely advised. The
      lesions were assessed for erythema, scaling, and induration (ESI) every 2 weeks
      for a total of 8 weeks. Patients with greater than 50% improvement were
      considered to have good improvement. Side-effects, if any, were also monitored.
      RESULTS: In Group A, 76.5% of patients (13/17) showed good improvement, whereas
      only 45.5% of patients (5/11) in Group B showed the same magnitude of improvement
      (P < 0.05). No side-effects were reported by any patient in either of the groups.
      CONCLUSIONS: Crude coal tar is a safe, effective, and inexpensive modality for
      the treatment of PPP. We recommend coal tar under occlusion, along with the
      liberal use of emollients, as the first line of therapy for all cases of PPP.

PMID- 9169339
TI  - Historic view of vitiligo in Korea.

PMID- 9169340
TI  - An unusual case of benign neonatal hemangiomatosis mimicking juvenile
      xanthogranuloma.

PMID- 9169341
TI  - Skin ulcers in a young woman on low-dose estrogen-combination pill.

PMID- 9169342
TI  - Droxicam photosensitivity with dyshidrotic hand dermatitis.

PMID- 9169343
TI  - Topical tretinoin as an adjunctive therapy with intralesional triamcinolone
      acetonide for alopecia areata. Clinical experience in northern Saudi Arabia.

PMID- 9169344
TI  - Regulation of osteoclast function.

PMID- 9169345
TI  - Hip fracture and osteoporosis in a XIIth Dynasty female skeleton from Lisht,
      upper Egypt.
AB  - Osteoporosis and complications arising from loss of bone mass have been present
      in human populations for thousands of years. However, reports of this disease in
      antiquity remain uncommon. The purpose of this report is to describe an important
      case of osteoporosis in ancient Egypt because of its intrinsic interest and to
      provide perspectives on factors contributing to this condition today. The case
      providing the focus for this report is from Lisht, Upper Egypt and is dated to
      the XIIth Dynasty (1990-1786 B.C.). Methods used to characterize the pathology
      include gross anatomical study, radiology, and radiographic measurements.
      Observations, measurements, and indices all indicate osteoporosis complicated by
      fracture of the femoral neck and compression fractures of some vertebrae. The
      Lisht case adds to a small corpus of reports on osteoporosis and complicating
      factors of this disease in antiquity. Long-term survival of an extracapsular
      fracture of the femoral neck in this case is remarkable and may reflect
      supportive social conditions.

PMID- 9169346
TI  - Modulation of the effects of glucocorticoids on collagen synthesis in fetal rat
      calvariae by insulin-like growth factor binding protein-2.
AB  - To test the hypothesis that insulin-like growth factors (IGFs) play a role in the
      response of bone to glucocorticoids, we determined the effects of cortisol on the
      incorporation of [3H]proline into collagenase-digestible protein (CDP) and
      noncollagen protein (NCP), the percent collagen synthesis, and the incorporation
      of [3H]thymidine into DNA of 21-day fetal rat calvariae cultured in the presence
      and absence of recombinant human insulin-like growth factor binding protein-2
      (IGFBP-2). At 24 h, cortisol (100 nM) increased CDP labeling and the percent
      collagen synthesis, and these effects were blocked by IGFBP-2 (1000 nM). At 24 h,
      cortisol decreased the incorporation of [3H]thymidine into bone, which was not
      affected by the addition of IGFBP-2. At 48 h, cortisol (1000 nM) decreased CDP
      labeling, which was maintained in the presence of IGFBP-2. At 48 h, IGFBP-2 alone
      decreased basal levels of CDP and NCP labeling and the percent collagen
      synthesis. Our data suggest that endogenous IGFs maintain basal levels of
      collagen synthesis and mediate the early stimulatory effect of glucocorticoids on
      collagen synthesis in fetal rat calvariae. However, blocking endogenous IGFs does
      not abrogate the inhibitory effect of glucocorticoids on DNA synthesis and the
      later inhibition of collagen synthesis in calvariae.

PMID- 9169347
TI  - Involvement of different second messengers in parathyroid hormone- and
      interleukin-1-induced interleukin-6 and interleukin-11 production in human bone
      marrow stromal cells.
AB  - Previous studies have suggested that increased secretion of bone active
      cytokines, such as interleukin-6 (IL-6) and interleukin-11 (IL-11), from
      osteoblasts and stromal cells play a pivotal role in the activation of
      osteoclasts and the genesis of osteoporosis. Various systemic and local factors
      can stimulate IL-6/IL-11 production, but the intracellular mechanism for such
      stimulation is largely unknown. In this study, we characterized the second
      messenger signaling in parathyroid hormone (PTH)- and IL-1-induced production of
      IL-6/IL-11 and studied the possible modulating effects of estrogen. rhPTH(1-34)
      and rhIL-1 alpha dose-dependently stimulated IL-6 and IL-11 production from human
      bone marrow stromal cells (hBMSCs). Agonists for protein kinase A (PKA)
      (forskolin), and protein kinase C (PKC) (phorbol 12-myristate 13-acetate; PMA)
      also stimulated IL-6/IL-11 production. Rp-diastereoisomer of adenosine cyclic
      3',5'-phosphorothioate (Rp-cAMPS) and H-8, inhibitors of PKA, significantly
      inhibited PTH-stimulated IL-6/IL-11 production, but did not inhibit IL-1
      stimulated IL-6/IL-11 production. In contrast, staurosporine and calphostin C,
      inhibitors of PKC, suppressed IL-1-stimulated, but not PTH-stimulated, IL-6/ IL
      11 production. Pretreatment of cells with 17 beta-estradiol (17 beta-E2)
      antagonized IL-1-stimulated IL-6 production. However, PTH-stimulated IL-6
      production and IL-1- and PTH-stimulated IL-11 production were not affected by 17
      beta-E2. Similarly, 17 beta-E2 inhibited PMA-stimulated IL-6 production, whereas
      neither forskolin-stimulated IL-6/ IL-11 production nor PMA-stimulated IL-11
      production was affected by 17 beta-E2. These results indicate that different
      second messengers are involved in PTH- and IL-1-induced IL-6 and IL-11 production
      by hBMSCs: PTH and IL-1 stimulate IL-6/IL-11 production via a PKA-dependent and
      PKC-dependent pathway, respectively. Furthermore, our results suggest that
      regulation of cytokine production by estrogen in hBMSCs is selective; only the IL
      1-induced IL-6 production, which is mediated by PKC pathway, is inhibited, but
      PTH-induced IL-6 production and PTH/IL-1-induced IL-11 production are not
      inhibited by estrogen.

PMID- 9169348
TI  - Altered regulation of parathyroid hormone secretion by calcium in pregnant and
      lactating rats.
AB  - We have previously shown that the serum parathyroid hormone (PTH) concentration
      in lactating (L) rats is not suppressed by high serum Ca2+ to the same extent as
      in nonmated (NM) rats. To investigate further Ca2+ regulation of PTH secretion,
      parathyroid cells from NM rats and rats in late pregnancy and at peak lactation
      were dispersed and incubated for 2 h in medium containing 0.52-2.05 mM Ca2+.
      Medium PTH was assayed with a homologous immunoradiometric assay (IRMA). At the
      two highest Ca2+ levels (1.81 and 2.05 mM), medium PTH was significantly higher
      (p = 0.031) for cells from L rats than for cells from NM rats. In contrast,
      significantly less (p < 0.001) PTH was secreted for the L group versus the NM
      group at medium Ca2+ values of 1.27 and 1.46 mM. Estimated set points for L and
      NM groups were 1.17 mM and 1.35 mM, respectively, corresponding closely to the
      prevailing serum Ca2+ for these two groups. Consistent with the present in vitro
      data, high serum PTH (> 40 pg/ml) in L rats occurred only at serum Ca2+ values
      below 1.27 mM. Elevated serum PTH at lower serum Ca2+ levels was also seen in
      pregnant rats. Dispersed parathyroid cells from 20- to 21-day pregnant rats
      secreted significantly more PTH (p = 0.028) than cells from NM rats at all Ca2+
      levels tested (1.1-1.6 mM). In conclusion, the relationship between extracellular
      Ca2+ and PTH secretion is altered in rats during late pregnancy and at peak
      lactation, perhaps as part of the adaptation to the demands for calcium for pre-
      and postnatal growth.

PMID- 9169349
TI  - Regulation of serum calcitriol by serum ionized calcium in rats during pregnancy
      and lactation.
AB  - Serum calcitriol concentrations in rats follow a biphasic pattern during
      reproduction, with elevated levels during late pregnancy, a decline after
      parturition, and a rise to even higher levels during peak lactation. We have
      previously shown that serum calcitriol in rats at peak lactation correlates
      significantly with, and appears to be regulated by, serum ionized Ca (Ca2+), with
      parathyroid hormone (PTH) serving a permissive role. We have extended this study
      by determining if serum calcitriol also correlates with serum Ca2+ during late
      pregnancy, when calcitriol levels are clearly elevated, and during early
      lactation, when only modest increases in serum calcitriol are observed. Analyses
      of data combined from nonmated, 21-day pregnant (P), and 1-day lactating rats (L)
      revealed a significant regression (p < 0.001) of calcitriol on Ca2+, but a
      nonsignificant regression (p = 0.34) of calcitriol on serum PTH. An even stronger
      correlation (p < 0.001) between calcitriol and Ca2+ was found for the combined
      data for 5-, 8-, and 14-day L rats. The partial correlation coefficient for
      calcitriol versus Ca2+, with PTH as the independent variable, was highly
      significant (p < 0.01) for the data from both combined groups. However, the
      coefficient for calcitriol versus PTH, with Ca2+ as the independent variable, was
      not significant (p > 0.05). Fetal weights (uterus and contents) correlated
      significantly with both maternal calcitriol and Ca2+ concentrations (p < 0.01),
      but not with maternal PTH levels. Litter weights for 14-day-old pups likewise
      correlated significantly with maternal calcitriol and Ca2+ (p < 0.001). We
      conclude that hypocalcemia, induced by the demands for Ca for fetal calcification
      and milk production, appears to be a controlling factor in serum calcitriol
      elevation in late pregnancy and throughout lactation, whereas PTH may be
      important for calcitriol synthesis without playing a direct regulatory role.

PMID- 9169350
TI  - A vitamin D receptor gene polymorphism in the translation initiation codon:
      effect on protein activity and relation to bone mineral density in Japanese
      women.
AB  - The effect of a T-C transition polymorphism at the translation initiation codon
      of the human vitamin D receptor (VDR) gene on the biological function of the
      encoded protein was investigated. Of 239 Japanese women volunteers subjected to
      genotype analysis for this polymorphism, 32 (13%) were genotype MM (the M allele
      is ATG at the putative translation start site), 75 (31%) were genotype mm (the m
      allele is ACG at the putative translation start site), and 132 (55%) were
      genotype Mm. The bone mineral density (BMD) in the lumbar spine (L2-L4) was
      determined for 110 healthy premenopausal women from the volunteers and was shown
      to be 12.0% greater (p < 0.05) for mm homozygotes than for MM homozygotes.
      Synthesis of the proteins by the M and m alleles from the cloned cDNAs in vitro
      and in transfected COS-7 cells revealed them to have a size of 50 and 49.5 kD,
      respectively, as determined by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. This size difference is consistent with initiation of
      translation of the M allele-encoded protein from an ATG codon located at
      nucleotides +10 to +12 in the conventional open reading frame. The extent of
      vitamin D-dependent transcriptional activation of a reporter construct under the
      control of a vitamin D response element in transfected HeLa cells was
      approximately 1.7-fold greater for the m type VDR than for the M type protein.
      These results suggest that the polymorphism at the translation start site of the
      VDR gene may modulate BMD in premenopausal Japanese women.

PMID- 9169351
TI  - Association between intestinal vitamin D receptor, calcium absorption, and serum
      1,25 dihydroxyvitamin D in normal young and elderly women.
AB  - The exact mechanism for the decrease in intestinal calcium absorption with age is
      not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D
      (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein
      concentration are possible causes. The objective of this study was to examine the
      effect of age on these factors. Fifty-nine young women age 25-35 years were
      compared with 41 elderly women age 65-83 years who underwent measurements of VDR,
      calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic
      hormones. Calcium absorption by both tests was lower in the elderly women
      compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR
      protein concentration were not significantly different between the two age
      groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in
      both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and
      with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did
      not correlate with calcium absorption in young women or elderly women, nor did
      VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary,
      the decrease in calcium absorption cannot be explained by a decrease in
      intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium
      absorption tests only accounts for 12-30% of the variance in the age-related
      change in the calcium absorption tests. Other factors, not yet understood, are
      responsible for the decline in calcium absorption with age.

PMID- 9169352
TI  - Peyronie's disease is associated with Paget's disease of bone.
AB  - Peyronie's disease is an idiopathic disorder in which an inflammatory fibrosis
      occurs in the tunica albuginea of the corpora cavernosa which causes the erect
      penis to become deformed. Peyronie's disease has a prevalence of 1% in men over
      age 50 years. Paget's disease of bone is a chronic skeletal disease with areas of
      increased bone turnover leading to pain, deformity, and in some cases arthritis.
      Because of a high rate of Peyronie's disease in subjects in a Paget's disease
      industry-sponsored drug trial, we asked whether there was an association between
      Peyronie's disease and Paget's disease of bone. We evaluated 61 men with Paget's
      disease attending our clinic for metabolic bone disease in a tertiary referral
      hospital, reviewed hospital records of all men discharged from our three
      hospitals with the diagnosis of Peyronie's disease, and mailed a validated
      questionnaire about shape of the erect penis to 1500 male members of the Paget
      Foundation. In the clinic population of men with Paget's disease of bone, 51 of
      61 (83.6%) reported having normal erections; 10 patients (16.4%) were impotent.
      Sixteen of the 51 men (31.4%) had developed a bend or deformity in their erect
      penis which was confirmed by a urologist's examination to be Peyronie's disease.
      When the men with Paget's disease with and without Peyronie's disease were
      compared, there was no difference in their ages, years with Paget's disease, or
      serum alkaline phosphatase level. Upon medical record review, 1 patient of 262
      (0.4%) with Peyronie's disease was found to have Paget's disease of bone. The men
      with Paget's disease returned their questionnaires for a response rate of 44.8%
      and reported Peyronie's disease with a prevalence of 14.5%. We suggest that
      Peyronie's disease is associated with Paget's disease of bone. Furthermore, we
      suggest that Peyronie's disease may be a previously unrecognized complication of
      Paget's disease of bone.

PMID- 9169353
TI  - The functional block of TNF but not of IL-6 prevents bone loss in ovariectomized
      mice.
AB  - Considerable evidence supports the hypothesis that estrogen prevents bone loss by
      blocking the bone marrow cell production of pro-osteoclastogenic cytokines.
      However, controversy remains on the role of candidate factors, such as tumor
      necrosis factor (TNF) and interleukin-6 (IL-6). To investigate the contribution
      of these cytokines to the pathogenesis of ovariectomy (OVX)-induced bone loss,
      OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor of
      TNF, the anti-(IL-6) antibody (Ab) 20F3, or estrogen for the first 2 weeks after
      surgery. OVX caused a rapid decrease in trabecular bone volume (TBV) and an
      increase in in vivo bone resorption, as assessed by bone histomorphometry.
      Treatment with TNFbp completely prevented bone loss and the increase in both
      osteoclast formation and bone resorption induced by OVX, but had no effects in
      sham-operated controls. In contrast, treatment with anti-IL-6 antibody failed to
      prevent bone loss, and the increase in bone resorption and osteoclastogenesis
      induced by OVX. These data demonstrate that in nongenetically manipulated mice,
      the estrogen-regulated cytokine that plays a central role in the mechanism by
      which estrogen deficiency causes bone loss is not IL-6, but rather TNF.

PMID- 9169354
TI  - Method-based differences in the automated analysis of the three-dimensional
      morphology of trabecular bone.
AB  - The three-dimensional (3D) morphology of trabecular bone is frequently quantified
      using computer programs. However, there are no standardized implementations of
      morphology programs and many variations are possible. Even though programs may
      use the same basic method, results can be significantly different because of
      differences in implementation. Morphology data from different laboratories
      therefore may not be comparable. The method of directed secants, with parallel
      plate assumptions, is commonly used to quantify 3D morphology. We examined the
      effect of several variations in the implementation of this method on measurements
      of trabecular plate number (Tb.N), trabecular thickness, and trabecular spacing.
      Three-dimensional micromagnetic resonance images of 10 bovine trabecular bone
      specimens were analyzed using several variations of the directed secant method.
      An analysis of covariance with repeated measures suggested that variations in the
      algorithm used to count test line intersections, variations in the criteria used
      to classify a test coordinate as bone or marrow, and variations in the number of
      test grid rotations had significant effects on Tb.N (p < 0.0001). The largest
      difference in Tb.N (52%) was due to the method used to count test line
      intersections with the bone-marrow interface. Variations in the classification
      algorithm and variations in the number of test line grid rotations resulted in a
      6% difference in Tb.N. The spacing of the test line grids did not affect Tb.N (p
      = 0.28), and all differences were independent of volume fraction (p = 0.67).
      These data show that there can be significant differences in trabecular bone
      morphology measurements due only to the method used for the measurements. To
      facilitate comparisons between laboratories, we have made validated computer
      programs to measure trabecular bone morphology available over the Internet.

PMID- 9169355
TI  - Histomorphometric assessment of bone mass, structure, and remodeling: a
      comparison between healthy black and white premenopausal women.
AB  - While noninvasive studies of bone mass and turnover in blacks and whites abound,
      histologic evaluations are very rare. We have performed a comparative bone
      histomorphometric study of iliac biopsies from 55 healthy, premenopausal women
      including 21 blacks (mean age 33.4 + 1.2 years) and 34 whites (mean age 32.5 +
      0.8 years) of comparable age, weight, body composition, education, and lifestyle.
      Biochemical indices of mineral metabolism: parathyroid hormone, 25-hydroxyvitamin
      D, 1,25-dihydroxyvitamin D, serum ionized calcium, serum phosphorus, and urinary
      calcium/creatinine were measured in the fasting state. Blacks had lower 25
      hydroxyvitamin D (315 +/- 3.36 vs. 63.21 +/- 3.79 nmol/l, p = 0.0001).
      Histomorphometric indices of bone volume, structure, and connectivity were not
      different between groups. The following indices of bone remodeling were also
      similar in both groups: eroded perimeter, osteoid width, mineralizing perimeter,
      tissue-based bone formation rate, osteoid maturation time, active formation
      period, and activation frequency. However, osteoid perimeter (black [B] = 15.85
      +/- 1.30 vs. white [W] = 9.49 +/- 0.70%, p = 0.0002), osteoid area (B = 2.55 +/-
      0.32 vs. W = 1.39 +/- 0.12%, p = 0.003), single-labeled perimeter (B = 5.46 +/-
      0.54 vs. W = 4.04 +/- 0.33%, p = 0.03), mineralization lag time (B = 38.18 +/-
      4.04 vs. W = 21.83 +/- 1.60 days, p < 0.009), and total formation period (B =
      148.15 +/- 19.70 vs. W = 84.04 +/- 7.62 days, p = 0.0056) were higher in blacks
      than in whites. The quiescent perimeter (B = 76.91 +/- 1.40 vs. W = 84.25 +/-
      0.91%, p = 0.0001), mineral apposition rate (B = 0.70 +/- 0.02 vs. W = 0.75 +/-
      0.02 micron/day, p = 0.066), mineralizing osteoid perimeter (B = 0.49 +/- 0.04
      vs. W = 0.75 +/- 0.04%, p = 0.0001) and adjusted apposition rate (B = 0.35 +/-
      0.04 vs. W = 0.58 +/- 0.04 micron3/micron2/day, p = 0.0001) were all lower in
      blacks than in whites. These results indicate that there are no differences in
      bone volume, microstructure, or turnover between black and white premenopausal
      women. However, there are significant differences in the mechanism of bone
      formation between the two groups, with a lower rate of mineralized matrix
      apposition within each remodeling unit and a longer total formation period in
      blacks than in whites. The differences appear to the result of more frequent
      and/or longer inactive periods in the life span of the bone formation units in
      blacks. These differences may allow a greater overall deposition of bone mineral
      in black women and therefore help explain a higher bone mass and perhaps better
      bone quality in black than white women.

PMID- 9169356
TI  - Resistance to bone resorbing effects of PTH in black women.
AB  - Black women have a lower incidence of vertebral and hip fractures than white
      women, possibly due to differences in skeletal and mineral metabolism. One
      suggested mechanism is that blacks have decreased skeletal sensitivity to
      parathyroid hormone (PTH). To test this hypothesis, we infused h(1-34)PTH in
      healthy premenopausal black (n = 15) and white (n = 18) women over 24 h and
      measured serum and urine indices of bone turnover and calcium metabolism
      throughout the infusion. At baseline, the mean 25-hydroxyvitamin D (25(OH)D)
      concentration was significantly lower in black women (46%). There were also
      nearly significant trends toward higher PTH and lower urinary calcium and
      pyridinoline levels in black women. During infusion, there were no racial
      differences in the mean (1-34)PTH levels achieved or in resultant elevations of
      serum calcium or 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. Endogenous
      parathyroid suppression (measured by (1-84)PTH levels) was also similar between
      blacks and whites. There was an initial decline in urinary calcium/creatinine in
      both groups with a greater reduction in black women early in the infusion period
      (p < 0.05 at 8 h). Furthermore, blacks had lower levels of urinary
      calcium/creatinine throughout the infusion (p < 0.05 group difference). Bone
      formation markers (carboxy-terminal propeptide of type I procollagen and
      osteocalcin) decreased within 8 h and continued to decline throughout the
      infusion with no distinguishable racial differences (p < 0.05 time trend for
      both). The most dramatic difference between black and white women in response to
      PTH infusion was represented by the bone resorption markers. Three separate
      metabolites of bone resorption (cross-linked N-telopeptide of type I collagen,
      cross-linked C-telopeptide of type I collagen, and free pyridinoline) all showed
      substantially greater elevations in white (mean peak increments 399, 725, and
      43%) compared with black women (mean peak increments 317, 369, and 17%) during
      the infusion (p < 0.05 group differences for all three variables). These data
      strongly suggest that blacks have decreased skeletal sensitivity to the acute
      resorptive effects of increased PTH. This finding indicates that calcium
      homeostasis may be accomplished in blacks (during times of relative calcium
      deficiency) by greater conservation of calcium from nonskeletal sources (most
      likely renal) with relative preservation of skeletal tissue. These differences in
      calcium economy could account, at least in part, for the increased bone mass and
      lower incidence of osteoporotic fractures in black women.

PMID- 9169357
TI  - Whole body bone, fat, and lean mass in black and white men.
AB  - This research describes the effects of age, ethnicity, and body size and
      composition on whole body bone mass and bone density in healthy black and white
      men. We measured 79 male subjects, 42 white and 37 black, ranging in age from 33
      to 64 years. Whole body bone mineral content (WBBMC) and bone mineral density
      (WBBMD), as well as fat and lean mass, were evaluated with a Hologic 1000W bone
      densitometer. We explore the utility of different methods of controlling for
      variations in body size in the two ethnic groups. There are statistically
      significant ethnic differences only in the bone mass variables. The black men had
      a 15% higher WBBMC (3111 vs. 2712 g, p < 0.0001) and a 8% higher WBBMD (1.25 vs.
      1.16 g/cm2, p = 0.001) than the white men. Dividing WBBMD by height reduced the
      black/white difference to 6%. WBBMC, WBBMC/height, and WBBMD are strongly and
      significantly correlated with weight, body mass index (BMI), and body
      composition; correlations tended to be lower for WBBMD/height. Age is not
      significantly correlated with any of the variables in either ethnic group (p > or
      = 0.10). In multivariate linear regression models for predicting WBBMC or WBBMD,
      the two best models contained height, weight, and an interaction of ethnicity and
      weight (model r2 = 0.72 for WBBMC and r2 = 0.47 for WBBMD); and height, lean
      mass, and an ethnicity-fat interaction (model r2 = 0.69 for WBBMC and r2 = 0.46
      for WBBMD). Using analysis of covariance, we found that controlling for lean mass
      and height reduced the black/white difference in bone mass from 14.7 to 9.8%.

PMID- 9169359
TI  - Strain gradients correlate with sites of periosteal bone formation.
AB  - We examined the hypothesis that peak magnitude strain gradients are spatially
      correlated with sites of bone formation. Ten adult male turkeys underwent
      functional isolation of the right radius and a subsequent 4-week exogenous
      loading regimen. Full field solutions of the engendered strains were obtained for
      each animal using animal-specific, orthotropic finite element models.
      Circumferential, radial, and longitudinal gradients of normal strain were
      calculated from these solutions. Site-specific bone formation within 24 equal
      angle pie sectors was determined by automated image analysis of microradiographs
      taken from the mid-diaphysis of the experimental radii. The loading regimen
      increased mean cortical area (+/-SE) by 32.3 +/- 10.5% (p = 0.01). Across
      animals, some periosteal bone formation was observed in every sector. The amount
      of periosteal new bone area contained within each sector was not uniform.
      Circumferential strain gradients (r2 = 0.36) were most strongly correlated with
      the observed periosteal bone formation. SED (a scalar measure of stress/strain
      magnitude with minimal relation to fluid flow) was poorly correlated with
      periosteal bone formation (r2 = 0.01). The combination of circumferential,
      radial, and longitudinal strain gradients accounted for over 60% of the
      periosteal new bone area (r2 = 0.63). These data indicate that strain gradients,
      which are readily determined given a knowledge of the bone's strain environment
      and geometry, may be used to predict specific locations of new bone formation
      stimulated by mechanical loading.

PMID- 9169358
TI  - Tartronates: a new generation of drugs affecting bone metabolism.
AB  - In the search for a new class of bone-sparing agents for treating osteopenic
      disorders, we hypothesized that tartronic acid derivatives, sharing the chemical
      characteristics both of bisphosphonates and of Gla residues contained in matrix
      proteins such as osteocalcin, could positively affect bone metabolism. A series
      of tartronates was therefore tested for their ability to affect bone metabolism.
      In vitro resorption tests were performed examining pit formation by freshly
      isolated rat and rabbit osteoclasts plated onto bone slices and exposed to the
      drugs for 48 h. Tartronates bearing a linear side-chain (DF 1222 and DF 1363A)
      were the most effective in inhibiting pit excavation in the pM-nM range.
      Tartronates did not affect osteoclast viability, number, adhesion, or tartrate
      resistant acid phosphatase activity. Transient cell retraction was observed in
      osteoclasts plated onto glass and exposed to DF 1222. The maximal effect was seen
      in cells treated for 4 h at a concentration of 1 pM. DF 1222 accelerated
      mineralization in cultures of periosteal cells without affecting other osteoblast
      like functions. This product was therefore tested in vivo in ovariectomized mice.
      Bone mass in femur was evaluated, by ash gravimetry, 21 days after ovariectomy.
      Unfortunately, DF 1222, the most active of tartronates in vitro, was inactive in
      this test because of its high hydrophilicity and the subsequent too short
      residence time. On the contrary, its tetrahydropyranyl ether derivative, DF
      1363A, endowed with a significantly higher lipophilicity, showed a dose-dependent
      bone-sparing effect when administered subcutaneously at 10, 30, and 100
      mg/kg/die, thus confirming the activity seen in in vitro tests. Because of their
      feasible parallel effect on both bone resorption and formation, tartronate
      derivatives may be tested to candidate this class of products for clinical
      studies.

PMID- 9169360
TI  - The effect of aging on bone formation in porous hydroxyapatite: biochemical and
      histological analysis.
AB  - The effect of aging on osteoblastic differentiation of marrow stromal stem cells
      was examined. Porous hydroxyapatite (HA) disks were soaked in cells suspensions
      of bone marrow cells from young (8 weeks) and old rats (60 weeks) and then
      implanted subcutaneously in syngeneic young and old rats. The bone marrow/HA
      composites were harvested 8 weeks later, and the contents of bone Gla protein
      (BGP) and alkaline phosphatase (ALP) activity in them were determined.
      Histologically, bone formation could be detected in all the composites in young
      recipient rats; however, some old bone marrow/HA composites in old recipients did
      not show bone formation and the bone volume in the young bone marrow/HA
      composites was greater than in the old bone marrow/HA composites. The ratios of
      ALP activities of young bone marrow/HA composites to old bone marrow/HA
      composites in young and old recipients were about five times and four times,
      respectively. The ratios of BGP contents of young bone marrow/HA to old bone
      marrow/HA composite in young and old recipients were about nine and eight times,
      respectively. The results suggest that the decreased bone formation observed in
      old bone marrow cells was due to a smaller population of stromal cells and/or
      decreased capacity of differentiation of stromal stem cells into osteogenic
      cells.

PMID- 9169361
TI  - Pseudopseudohypoparathyroidism, presenting with osteoma cutis.

PMID- 9169362
TI  - Port-access bilateral internal mammary artery grafting for left main coronary
      artery disease: canine feasibility study.
AB  - BACKGROUND: To extend the applications of minimal access cardiac surgery, an
      endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia
      delivery and cardiac venting was used to perform bilateral internal mammary
      artery (IMA) bypass grafting in six dogs. METHODS: The left IMA (LIMA) was taken
      down thoracoscopically from three left lateral chest ports, followed by the right
      IMA (RIMA) from the right side. One left-sided port was extended medially 5 cm
      with or without rib resection, to expose the pericardium. Both IMAs were divided
      and exteriorized through the left anterior mediastinotomy. Flow and pedicle
      length were satisfactory in all cases. Femoral-femoral bypass was used and the
      heart arrested with antegrade delivery of cardioplegic solution via the central
      lumen of a balloon catheter inflated to occlude the ascending aorta. All
      anastomoses were made through the mediastinotomy under direct vision. In five
      studies the RIMA was attached to the left anterior descending artery (LAD) and
      the LIMA to the circumflex, and in one study the RIMA was tunneled through the
      transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All
      animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was
      108 +/- 27 minutes (mean +/- SD) and the clamp duration was 54 +/- 10 minutes.
      RESULTS: Preoperative and postoperative cardiac outputs were 2.9 +/- 0.71/min and
      2.4 +/- 0.31/min, respectively (p = NS), and corresponding pulmonary artery
      occlusion pressures were 6 +/- 3 mmHg and 7 +/- 2 mmHg, respectively (p = NS).
      All 12 grafts were demonstrated to be fully patent. Postmortem examination
      revealed well aligned pedicles and correctly grafted target vessels. CONCLUSION:
      This canine model demonstrates the potential for a less invasive approach to the
      surgical management of left main coronary artery disease in humans.

PMID- 9169363
TI  - Mitral valve reconstruction and mitral valve replacement for ischemic mitral
      insufficiency.
AB  - BACKGROUND: Patients with ischemic mitral incompetence have a high operative risk
      whether the valve is repaired or replaced. The advantage of repair over
      replacement is unclear in this group of patients. METHODS: Between April 1986 and
      December 1994, 232 patients underwent surgery for ischemic mitral valve
      insufficiency; mitral valve replacement was performed in 98 of them. Operative
      mortality was 13.3%. The actuarial survival rate after 5 years was 73.3%. The
      surgical risk in patients whose left ventricular ejection fraction (LVEF) was 10%
      30% (operative mortality 50.0%) was higher than in those whose LVEF was greater
      than 30%. Valve reconstruction was performed in 102 patients. Operative mortality
      in this patient group was 14.7%. The surgical risk in patients whose LVEF was <
      or = 30% was higher (operative mortality 42.9%). RESULTS: The total actuarial
      survival rate of all patients was 64.4% after 5 years. Mortality during follow-up
      was higher in patients with residual mitral valve insufficiency greater than
      grade I after mitral valve reconstruction. Twenty-four patients with severely
      impaired left ventricular function underwent heart transplantation. Operative
      mortality in this group was 12.5%. Eight patients received left ventricular
      aneurysmectomy in addition to valve surgery, three of them died early.
      CONCLUSIONS: We conclude that patients with highly impaired left ventricular
      function and ischemic mitral insufficiency are at too great a risk for either
      valve reconstruction or replacement. Cardiac transplantation should be considered
      for this patient group. However, patients with ischemic mitral insufficiency and
      moderately impaired left ventricular function can undergo valve reconstruction or
      replacement with an acceptable prognosis. The goal of mitral valve reconstruction
      should be reducing mitral valve insufficiency to at least grade I. If this is not
      achieved, the prognosis after repair is worse than after valve replacement,
      therefore, the surgeon should replace the valve without delay.

PMID- 9169364
TI  - Randomized, placebo-controlled, double-blind study of an ultra-low-dose aprotinin
      regimen in reoperative and/or complex cardiac operations.
AB  - BACKGROUND AND AIM OF THE STUDY: High-dose aprotinin is an effective but costly
      method to reduce transfusions after cardiopulmonary bypass (CPB). Very low doses
      of aprotinin have been shown to be effective in primary cardiac surgery, but not
      in patients undergoing procedures associated with the greatest usage of
      allogeneic blood products after CPB. We evaluated the efficacy of ultra-low-dose
      aprotinin in this patient population. METHODS: Aprotinin 1 million KIU or placebo
      was added to the priming solution of the CPB circuit of 52 patients undergoing a
      reoperation and/or a complex surgical procedure. Dryness of operative field,
      hemoglobin concentrations, coagulation parameters, chest drainage, and
      transfusion requirements were compared. RESULTS: Total chest drainage was not
      different between groups, but fewer patients in the aprotinin group required
      additional protamine postoperatively (35% vs 69% for controls, p = 0.03) and
      fewer received fresh frozen plasma (FFP; 19% vs 46% for controls, p = 0.04). Red
      cell transfusion was smaller in the aprotinin group compared to placebo (median 4
      and 2 units, respectively, p = 0.04). Transfusion of FFP, platelets,
      cryoprecipitates was not different between groups. Total number of units
      transfused tended to be reduced in the aprotinin group compared to control
      (median 2 and 7 units, respectively, p = 0.06). CONCLUSIONS: Prophylactic
      administration of ultra-low-dose aprotinin reduced transfusions in patients
      undergoing repeat operations or complex procedures. Aprotinin could be used in a
      more economical manner, even in this patient population at high-risk of receiving
      allogeneic blood products.

PMID- 9169365
TI  - Clinical implications of short-axis aortopulmonary rotation on juxtacommissural
      origin of the coronary artery in transposition of the great arteries and surgical
      strategy.
AB  - BACKGROUND: The relationship of short-axis aortopulmonary rotation (APR) with
      juxtacommissural origin of the coronary arteries (JOCA) in transposition of the
      great arteries (TGA) has never been elucidated. The surgical outcome of arterial
      switch operation (ASO) is influenced by the presence of JOCA. METHODS: Fifteen
      patients with TGA who presented to our institution between 1988 and 1995, and 23
      cases from the literature, all with documented JOCA and APR, were analyzed. Each
      coronary arterial type was assigned to one of five patterns, according to
      similarities of epicardial configuration. All our patients underwent an ASO with
      various techniques to deal with JOCA. RESULTS: JOCA near the facing commissure
      (FC, 35 cases), were more frequent with anterior TGA (29/31, 94%) except types
      5cj and 9j that were seen with posterior and right lateral TGA (4/4, 100%);
      whereas JOCA near the right-hand nonfacing commissure (RNC, 3 cases) were related
      with posterior TGA. Eta-square analysis showed significant correlation between
      various JOCA and short axis APR. Thirteen of our cases had JOCA near FC, two near
      RNC. Five of the former in whom the coronary artery was excised as a single
      button had a superior trapdoor; using a two-button technique three of the former
      had a lateral funnel and one of the latter had a medial trapdoor for the JOCA;
      all survived although on late noncoronary death was noted. In the remaining six
      cases without augmentation, only one survived (8/1 vs 1/5, p < 0.02). CONCLUSION:
      JOCA in TGA was related to short axis APR, generally near FC in anterior TGA
      (except types 5cj and 9j), and near the RNC in posterior TGA. A superior
      (lateral) or medial flap, to augment the coronary button for JOCA near FC or RNC
      is helpful for a successful ASO.

PMID- 9169366
TI  - Total extracardiac right heart bypass using a polytetrafluoroethylene graft.
AB  - BACKGROUND: With regard to hemodynamics and late arrhythmias, total cavopulmonary
      connection has been accepted as a superior technique as compared to Fontan type
      procedures. However, intra-atrial baffles for lateral tunnel or conduit remain
      construction retain some similar disadvantages. PATIENTS AND METHODS: As an
      alternative to total cavopulmonary connection, total extracardiac right heart
      bypass using a polytetrafluoroethylene tube for the inferior vena cava to
      pulmonary artery connection may obviate some problems. Five patients with complex
      heart disease necessitating one ventricle repair underwent this procedure
      successfully. RESULTS: Aortic cross-clamp time ranged from 0 to 24 minutes (mean
      = 15.8 min). No case required takedown or an additional step. Although the follow
      up periods have been relatively short (mean = 19 months), all patients are well
      and no arrhythmic event or thromboembolic episode has occurred. CONCLUSIONS: As a
      simple, safe, and reproducible procedure, total extracardiac right heart bypass
      is an alternative to Fontan or total cavopulmonary connection procedure.

PMID- 9169367
TI  - Cavo atriopulmonary anastomosis via a nonprosthetic medial tunnel.
AB  - A surgical technique is described to perform a total bypass of the venous
      ventricle (TBPVV) via a cavo atriopulmonary anastomosis wherein a medial atrial
      tunnel is constructed using autologous tissue. The procedure offers the advantage
      of maintaining low atrial pressure at the sinus node area without the use of
      prosthetic material. It also represents a good method for conversion of a
      bidirectional Glenn to a TBPVV avoiding surgical damage of the sinus node area.

PMID- 9169368
TI  - Coarctation in teenagers: two new surgical modifications.
AB  - BACKGROUND: Definitive surgical procedure for correction of aortic coarctation
      presenting initially in teenagers, remains an issue. Classic subclavian
      angioplasty as described by Waldhausen is not recommended after the age 1 or 2
      years. Prosthetic patch angioplasty has been associated with an unacceptable
      incidence of aneurysm formation and resection with end to end anastomosis is not
      always easy, owing to the development of friable collaterals. METHODS: In the
      last 4 years, we have utilized two surgical modifications for the treatment of
      primary isolated coarctation in teenagers. The first is aortoplasty, which relies
      on minimal resection of the coarctation segment and a plastic procedure of
      creating four identical flaps from the proximal and distal aorta, the
      interlocking of which will restore aortic lumen. The second modification is the
      use of a classic subclavian flap aortoplasty with the addition of a Gore-Tex
      graft, anastomosed between the upper lateral opening in the suture line and the
      distal left subclavian artery. Additionally, for the treatment of recurrent
      coarctation associated with cardiac anomalies, we have utilized the use of adult
      sized extra-anatomical conduit interposed between the ascending and the
      descending aorta. RESULTS AND CONCLUSIONS: All three procedures have yielded
      gratifying results and we believe will increase the options available for the
      surgeon treating teenagers' coarctation.

PMID- 9169369
TI  - Supravalvular stenotic mitral ring with ventricular septal defect.
AB  - BACKGROUND: Supravalvular mitral ring is exceedingly uncommon. METHODS: We report
      a 4-year-old girl with supravalvular stenotic mitral ring and ventricular septal
      defect (VSD). The VSD was closed by a Dacron patch and the supravalvular ring was
      excised. For treatment of supravalvular mitral ring with obstruction, surgical
      resection is commonly performed. RESULTS: There are no reports of long-term
      follow-up after resecting the supravalvular mitral ring. CONCLUSION: In our case,
      no mitral stenosis was evident on postoperative echocardiogram performed 3 years
      after surgery.

PMID- 9169370
TI  - Metastatic mucinous adenocarcinoma of the heart.
AB  - A case of metastatic mucinous adenocarcinoma to the heart is described. The
      patient presented with neurological symptoms consistent with an embolic
      cerebrovascular accident. Evaluation by the referring cardiologist at that time
      showed what appeared to be a left atrial myxoma. In a review of the English
      language medical literature, no other case of this nature was found.

PMID- 9169371
TI  - Surgical treatment of recurrence of an aneurysm of aberrant right subclavian
      artery.
AB  - A 52-year-old woman underwent incomplete resection of an aneurysm of the aberrant
      right subclavian artery. Three years later she was hospitalized because of a
      right superior mediastinal mass on the chest X-ray and a new angiography revealed
      dilatation of the remaining part of the aberrant right subclavian artery near its
      origin and involving the adjacent thoracic aorta and the distal aortic arch. At
      surgery, a left posterolateral thoracotomy in the fourth intercostal space was
      performed. Using deep hypothermia and circulatory arrest the aneurysm was excised
      and the aortic tract adjacent to the aneurysm was replaced with a Dacron
      prosthesis.

PMID- 9169372
TI  - Temporary mechanical support with the BVS 5000 assist device during treatment of
      acute myocarditis.
AB  - BACKGROUND: Ventricular support with the BVS 5000 (Abiomed) has been used as
      temporary circulatory assist for the failing heart. Our purpose is to summarize
      four cases illustrating the role of mechanical unloading in acute myocarditis.
      METHODS: Four patients aged 16- to 33-year old presented with congestive heart
      failure 4 to 20 days after a flu-like syndrome. All patients were in severe
      cardiogenic shock +/- renal and liver dysfunction. Ejection fraction ranged from
      5% to 26%. Indications for ventricular assist were failure of maximal medical
      treatment with > or = two inotropes +/- intra-aortic balloon pump. Myocardial
      biopsy revealed acute myocarditis in three patients and severe edema in one
      despite a characteristic clinical course. Two patients received immunotherapy
      with OKT3. Biventricular assist was used in three patients and left ventricular
      assist only was used in one. Mean support time was 8.3 days (7 to 11). RESULTS:
      All patients had recovery of myocardial function and were discharged from the
      hospital in good condition. CONCLUSION: The BVS 5000 device provides a safe,
      simple, and effective method to support the circulation during acute myocarditis.
      We hypothesize that this may facilitate myocardial recovery by decompressing the
      distended ventricle. Ventricular assist devices should be used early in the
      presence of hemodynamic deterioration on maximal medical therapy.

PMID- 9169373
TI  - A model for developing effective treatments: progression and interplay of theory,
      research, and practice.
AB  - The central thesis of this article is that advances in psychotherapy research for
      children and adolescents are limited, despite the large number of controlled
      studies and consistent conclusions about demonstrated effectiveness. The ways in
      which individual studies are conducted and the lack of an overall plan for the
      progression of research to identify effective treatments have contributed to the
      limited conclusions. In this article, I identify steps toward developing
      effective treatment that entail conceptualization and investigation of clinical
      problems, processes of change, and conditions that influence treatment outcome.
      Progress will not only require more systematic accretion of research, but also
      expansion in the range of questions, outcomes, and models of treatment delivery
      that are examined. Efforts to improve the knowledge base and to integrate
      knowledge into clinical practice can also be greatly enhanced by modifying the
      ways in which clinical work is conducted and specifically by systematically
      monitoring treatment implementation and patient progress.

PMID- 9169374
TI  - Life stressors, neighborhood disadvantage, and resources: a focus on inner-city
      children's adjustment.
AB  - Examined the contribution of particular stressors and resources to inner-city
      children's adjustment. Fourth, 5th, and 6th graders (N = 315; 66% from ethnic
      minority groups) reported on their recent exposure to stressful events and
      neighborhood disadvantage, their perceptions of self-worth and social support,
      and their behavioral and academic adjustment. Hierarchical regressions indicated
      unique contributions of stressful events and neighborhood disadvantage to
      predicting antisocial behavior; higher levels of self-worth and family support
      were related to lower levels of antisocial behavior, but higher levels of peer
      support were related to higher levels of antisocial behavior. Furthermore,
      whereas family support buffered the relation between stressful events and
      antisocial behavior, peer support exacerbated the effect of stressors on
      behavioral maladjustment.

PMID- 9169375
TI  - Peer relationships of young children: affiliative choices and the shaping of
      aggressive behavior.
AB  - Examined the occurrence of selective peer affiliation, and its impact on the
      development of aggressive behavior in four classrooms serving 72 preschool-age,
      high-risk boys and girls. Children classified as aggressive and nonaggressive
      were both highly selective in their peer affiliations, spending the majority of
      their time with a few same-sex classmates. Children generally established strong,
      stable, mutual affiliations with peers similar to themselves in aggression, but
      aggressive children had more difficulty establishing such affiliations. The
      interaction of peer dyads containing at least one aggressive child were
      characterized by more frequent, lengthy, and intense conflicts regardless of the
      affiliative relationship characterizing the dyad. The amount of time children
      spent interacting with aggressive peers predicted changes in observed and teacher
      rated aggressiveness 3 months later.

PMID- 9169376
TI  - Buffering children from marital conflict and dissolution.
AB  - Examined several protective mechanisms that may reduce deleterious correlates of
      marital conflict and marital dissolution in young children. One set of potential
      buffers focused on parent-child interaction: parental warmth, parental
      scaffolding/praise, and inhibition of parental rejection. As a second set of
      potential buffers, each parent was interviewed about their "meta-emotion
      philosophy"--that is, their feelings about their own emotions, and their
      attitudes and responses to their children's anger and sadness. The third set of
      potential buffers concerned intraindividual characteristics of the child,
      including the child's intelligence and regulatory physiology (basal vagal tone
      and vagal suppression). Fifty-six families with a preschool child were studied at
      two time points: when the children were 5 years old (Time 1) and again when the
      children were 8 years old (Time 2). At Time 1, naturalistic observations of
      marital and parent-child interaction were conducted and assessment of child
      regulatory physiology was obtained through measures of basal vagal tone and
      suppression of vagal tone. Parents were also interviewed individually about their
      feelings about their own and their children's emotions, and children's
      intelligence was assessed. At Time 2, assessment of child outcomes were obtained,
      including observations of peer interaction, mother ratings of behavior problems
      and mother and teacher ratings of peer aggression, mother ratings of child
      physical illness, and measures of achievement. Results indicated that all Time 1
      buffering factors protected children in face of marital conflict and dissolution.

PMID- 9169377
TI  - Social problem solving in hyperactive-aggressive children: how and what they
      think in conditions of automatic and controlled processing.
AB  - Examined how and what children think under conditions of automatic and controlled
      processing within the context of social problem solving. In a condition that
      elicited automatic processing, hyperactive-aggressive children did not differ in
      being able to identify the components of a problem or in the number of solutions
      generated to solve a problem, but were more aggressive in the types of solutions
      generated, as compared to nonhyperactive-nonaggressive children. Furthermore, in
      a condition eliciting controlled processing, hyperactive-aggressive children did
      not differ in identifying problem components, generating solutions, or in
      anticipating outcomes for solutions, but were less able to anticipate
      consequences, and were more aggressive in choosing a best solution to solve a
      problem, as compared to nonhyperactive-nonaggressive children. The study
      demonstrated a relation between problem-solving codes that discriminated between
      groups, and overall child adjustment. Implications for social problem-solving
      interventions are discussed.

PMID- 9169378
TI  - Worrisome thoughts in children clinically referred for anxiety disorder.
AB  - Administered a 31-item worry measure, based on criteria from the Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric
      Association, 1987) for anxiety disorders, to referred children with anxiety
      disorders (n = 72) or attention deficit hyperactivity disorder (ADHD; n = 50),
      and to nonreferred, never psychiatrically ill controls (n = 55). Anxiety and ADHD
      groups did not differ for self-reported worries. Anxious children did report more
      "intense" worries about separation and social evaluation than controls. ADHD
      children reported more intense worries about friends and school than controls.
      Separation worries were most prevalent in children with separation anxiety
      disorder, thus distinguishing this subgroup from both control groups. Results
      suggest that intense worries specific to one's anxiety disorder are more
      clinically relevant than the overall level of worry. Implications for assessment
      of worry are discussed.

PMID- 9169379
TI  - An investigation of negative affectivity in Australian adolescents.
AB  - Investigated the relation between anxiety and depression in a sample of 783
      nonreferred adolescents from metropolitan and rural areas of Melbourne,
      Australia. Participants were administered the Revised Children's Manifest Anxiety
      Scale (Reynolds & Richmond, 1985) and the Reynold's Adolescent Depression Scale
      (Reynolds, 1986). Correlations showed that anxiety and depression were closely
      related. However, exploratory factor analyses revealed that depression and
      anxiety items loaded on separate and quite distinct factors. These findings are
      discussed with reference to the construct of negative affectivity and Clark and
      Watson's (1991) tripartite model of anxiety and depression.

PMID- 9169380
TI  - Effect of co-occurrence on the referability of internalizing and externalizing
      problem behavior in adolescents.
AB  - Assessed the effect of co-occurring versus not co-occurring internalizing and
      externalizing behavior problems on the reasons parents reported for clinical
      referral of their adolescent child. Reasons for referral were coded for 181
      inpatient adolescents, and parent ratings of internalizing and externalizing
      behavior were obtained for a general population sample of 500 adolescents.
      Parents concurrently reported internalizing and externalizing behavior as reasons
      for referral less frequently (p < .0001) than would be expected given the
      correlation between these two domains in the general population sample. This
      suggests that the presence of externalizing problems may decrease parents'
      concern or awareness of internalizing problems, the presence of internalizing
      problems may decrease parents' concern or awareness of externalizing problems, or
      both. Implications for the clinical referral of adolescents and for informal
      parental efforts at helping their children with externalizing and internalizing
      problems are discussed.

PMID- 9169381
TI  - Perceived relationships with parents among adolescent inpatients with depressive
      preoccupations and depressed mood.
AB  - Hypothesized that two types of "depressogenic" preoccupations (self-critical and
      interpersonal), measured by the Depressive Experiences Questionnaire for
      adolescents (DEQ-A; Blatt, Shaffer, Bars, & Quinlan, 1992), would mediate
      associations between perceived difficulties with parents and adolescent
      depression. Adolescent inpatients between 11 and 17 years of age (N = 295; 158
      girls) in an acute-care psychiatric hospital completed the DEQ-A, a Reynolds
      (1986, 1989) depression questionnaire, and measures that assess experiences of
      alienation (vs. dependency) and separation-individuation conflicts in the
      adolescent-parent relationship. Alienation and counterdependency in relation to
      parents were associated with self-critical concerns; excessive closeness and
      dependency with interpersonal concerns; and separation-individuation conflicts
      with both types of concerns. Self-critical and interpersonal concerns were linked
      to adolescent depression and accounted for most of the variance initially
      explained by difficulties with parents.

PMID- 9169382
TI  - Clinically referred children and adolescents: fathers, family constellations, and
      other demographic factors.
AB  - Investigated the likelihood that clinically referred youth have contact with
      their biological father. Family demographics such as family constellation,
      race/ethnicity, and socioeconomic status were also explored. Based on 356
      consecutive therapy and assessment referrals to an outpatient clinic, slightly
      less than half (42.4%) of the children and adolescents referred due to
      psychological problems and more than half (67.8%) of the youth referred due to
      learning difficulties lived with both their biological mother and biological
      father. For those who did not live with both of their biological parents, 40.0%
      and 56.0%, respectively, had regular face-to-face contact with both biological
      parents. These figures suggest that, although the percentages of intact families
      are somewhat lower in treatment samples than in the general population or in a
      sample referred for learning difficulties, close to half of clinically referred
      youth continue to live with both of their biological parents. Future directions
      for the inclusion of fathers in clinical research are discussed.

PMID- 9169383
TI  - A Rorschach comparison of psychopathic and nonpsychopathic conduct disordered
      adolescents.
AB  - Forty-eight male subjects who met the DSM-IV (APA, 1994) criteria for conduct
      disorder (CD) were assessed for psychopathy level using a modified version of the
      Psychopathy Checklist-Revised (PCL-R, Forth, Hart, & Hare, 1990). Rorschach
      variables associated with self-perception, affects, and object relations, early
      behavioral problems and history of violence were compared between psychopathic
      and nonpsychopathic CD adolescents. Psychopathic CD subjects were significantly
      more self-centered and violent than nonpsychopathic CD subjects. Decreased
      attachment and anxiety were found in both CD groups. Our study adds empirical
      support to the heterogeneity noted among CD adolescents (PCL-R), supports the
      utility of the Rorschach for detecting individual differences among CD subjects,
      and extends the empirical work of Gacono and Meloy (1994) to adolescent
      psychopathy.

PMID- 9169384
TI  - Gender and drug differences in antisocial personality disorder.
AB  - The relation between childhood behavior disorders (CBD), attentional difficulties
      (ADD), and antisocial personality disorder (ASP) was examined in a clinical
      population of alcoholics and polysubstance abusers. Polysubstance abusers
      reported increased CBD symptomatology, increased attentional problems, a higher
      rate of ASP, and a greater number of both current and lifetime ASP symptoms
      relative to alcoholics without polysubstance abuse. An examination of gender
      effects revealed significant differences on self-reported adult attentional
      problems, with females endorsing a greater number of items. As a group, females
      exhibited the highest rate of ASP. Males showed a significant correlation between
      current ASP symptoms and both attention and conduct problems in early childhood.

PMID- 9169385
TI  - Expressive communicative ability, symptoms of mental illness and aggressive
      behavior.
AB  - The role of expressive communicative ability and level of mental illness symptoms
      in predicting aggressive behavior was explored in 67 adults with mental
      retardation. Overall rates of aggression were low with dangerous aggression more
      the exception than the rule. However, a subset of aggressive behaviors appeared
      to exist as a continuing risk for injury to others. Both expressive communicative
      ability and level of mental illness symptoms were strong predictors of aggressive
      behavior. In combination, high mental health symptoms and low expressive
      communicative ability were associated with the greatest prevalence of aggression.

PMID- 9169386
TI  - Relationships among child abuse, date abuse, and psychological problems.
AB  - Data on child abuse, date abuse and psychological problems were gathered from the
      same participants, 133 female undergraduates, in order to better examine possible
      relationships among the variables. Verbal abuse in childhood or on dates was
      examined as well as physical and sexual abuse. Factors influencing whether people
      remain in or leave abusive relationships were examined, along with possible
      mediators of the relationships between child abuse, date abuse, and psychological
      problems. Verbal, physical, and sexual child abuse were all associated with an
      increased risk of later date abuse or psychological problems. Abuse by a date was
      also associated with psychological problems. Low self-esteem and anger may have
      played mediating roles.

PMID- 9169387
TI  - Attributions of responsibility in father-daughter incest in relation to gender,
      socio-economic status, ethnicity, and experiential differences in participants.
AB  - One hundred and fifty-seven state college undergraduates (84 females and 73
      males) answered the Jackson Incest Blame Scale [JIBS] modified to include mother
      blaming after reading one of four vignettes about father-daughter incest in high
      or low SES White or Black families. Responses about incest prevalence (created
      for this study) in families with different ethnic and SES backgrounds varied with
      gender and SES of participants. Gender differences include blame of offender,
      situation, victim, and mother on the modified JIBS. Parents blamed the offender
      more than non-parents. Participants who knew an incest survivor disagreed
      significantly more with victim-blaming statements than those who did not know a
      survivor of incest.

PMID- 9169388
TI  - Non-referral of psychopathological child firesetters to mental health services.
AB  - The present study attempted to determine if those children with significant
      psychopathology were referred to mental health services after having initially
      been referred to the fire department. On file at the Portland Fire Department
      were 30 child firesetters whose parent or guardian had completed the Child
      Behavior Checklist. The CBCL had not been scored prior to the fire department's
      treatment referral, or prior to our review of the files. Significant
      psychopathology, determined after the CBCL had been scored, was not a determinant
      of future referral for mental health services. Thus, there is a need for fire
      departments and mental health professionals to work collaboratively to determine
      the appropriate treatment referral for child firesetters.

PMID- 9169389
TI  - Cognitive imbalance and antisocial personality characteristics.
AB  - A cognitive imbalance, in which intellectual functioning is elevated in the
      performance area in comparison to verbal IQ, has been posited as an antecedent
      condition in relation to antisocial behaviors. The current investigation was
      based on the notion of a developmental arrest in which verbal, analytical,
      controlling brain processes (analogous to verbal IQ) fail to develop
      commensurately with the more impulsive actions mediated by the motor areas of the
      cerebral cortex (analogous to performance IQ). The simple verbal IQ performance
      IQ discrepancy index used in prior studies was reformulated as a causal
      theoretical model consisting of shared and unique performance IQ variance. The
      participants were 325 adults including 141 prison inmates. They were administered
      the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Psychopathic
      Deviate (Pd) and Mania (Ma) scales of the Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2). These were the manifest (measured) variables in the model
      tested by means of structural equation modeling procedures. Several statistical
      indices suggested an excellent model-data congruence.

PMID- 9169390
TI  - Immediate antecedents to adolescents' offenses.
AB  - The current research examined importance ratings by adolescent offenders of
      immediate antecedents to their offenses. One hundred and fifteen adolescent
      offenders consecutively admitted to an inpatient psychiatric unit for court
      ordered assessment completed the High Risk Situations Questionnaire for Young
      Offenders (HRSQ-YO), an instrument designed to assess the self-reported
      importance of various antecedents to a past, highly salient, offense. Principal
      components analysis of responses to the 71 items of the HRSQ-YO resulted in three
      factors which were rotated to a varimax criterion and labelled Negative
      Affectivity, Delinquency, and Aggressivity. Delinquency factor scores were
      significantly higher for property offenses than for violent offenses, whereas
      Aggressivity factor scores were significantly higher for violent offenses than
      for property offenses. Negative Affectivity factor scores did not differ between
      property and violent offenses. Implications of the results for relapse prevention
      approaches to the reduction of recidivism among adolescent offenders are
      discussed.

PMID- 9169391
TI  - A cognitive approach to validation of the fixated-regressed typology of child
      molesters.
AB  - The fixated/regressed typology of child molesters has been widely used in
      classifying molesters. Although the terminology is psychodynamic in origin,
      cognitive correlations for the two types can be identified. A research instrument
      designed to assess child molester cognitions, attitudes, and background
      characteristics was administered to 94 molesters, one-third of whom had been
      identified as fixated and two-thirds as regressed. Data analysis yielded results
      which were generally supportive of the criteria for the two types. Fixated
      molesters were likely to be more child-centered, to molest male children outside
      the family, to come from "broken" homes, and to use alcohol less frequently than
      regressed molesters. Regressed molesters were likely to be better adjusted, to
      molest female children outside the family and to come from intact homes.

PMID- 9169392
TI  - Psychosocial characteristics of subtle and blatant racists as compared to
      tolerant individuals.
AB  - Studies in psychology have demonstrated that tolerant individuals demonstrate
      good psychological health and prejudiced individuals demonstrate poor
      psychosocial functioning. Past investigations have shown disturbances in
      interpersonal relationships for prejudiced individuals in childhood. Blatant
      racists aggressively assert that members of minority groups are inferior. Subtle
      racists blame social inequities on minority group cultures and customs. A
      questionnaire to distinguish tolerant individuals from blatant and subtle racists
      was employed. Tolerant individuals were shown to be psychologically healthier
      than both blatant and subtle racists. Both blatant and subtle racists show
      maladaptive patterns in psychosocial functioning. Both blatant and subtle racists
      report predicted disturbances in parental relationships, as well as insecure and
      hostile ties with peers.

PMID- 9169393
TI  - Serum testosterone in adult sex offenders: a comparison between Caucasians and
      North American Indians.
AB  - Patients admitted to the Phoenix Program for sex offender treatment at Alberta
      Hospital Edmonton were separated by family history into a group of North American
      Indians and a group of Caucasians, with respective sample sizes of 53 and 192
      after range matching the Caucasian to the North American Indian sample on a
      number of demographic variables. Controlling for body mass index and age, the two
      groups were equivalent in terms of 12 basic blood chemistry variables and 5 of 6
      endocrine measures. Serum testosterone did differ significantly (p < .0005,
      covariate adjusted means of 22.3 and 26.5 nmol/L, respectively, for Caucasians
      and North American Indians). Further research will be required to establish the
      generality of this result and to ascertain the etiology.

PMID- 9169394
TI  - Peer, family, and motivational influences on drug treatment process and
      recidivism for probationers.
AB  - Treatment efforts appear to be effective in reducing crime among drug using
      individuals, but components of the treatment process associated with client
      improvement need to be identified. Furthermore, these elements of treatment may
      play an intermediate role in the connection between client background
      characteristics and later criminal activity. The current study examines a
      structural equation model including client perceptions of their drug related
      problems, peer deviance, and family dysfunction as influences upon the formation
      of therapeutic relationships during treatment and rearrests following treatment.
      Results showed therapeutic relationships were positively associated with
      recognition of drug related problems and negatively related to rearrest. Peer
      deviance also was positively related to rearrest.

PMID- 9169395
TI  - The Criminal Sentiments Scale: predictive validity in a sample of violent and sex
      offenders.
AB  - This study investigated the predictive validity of the Criminal Sentiments Scale
      (CSS: Gendreau, Grant, Leipciger, & Collins, 1979) within a sample of violent and
      sex offenders using conviction and failure on conditional release as the
      criterion variables. The CSS was completed by 130 male offenders (65 sex
      offenders and 65 violent offenders) commencing a sentence of greater than two
      years in a Canadian federal institution. Average time at risk for the sample was
      16 months. Arrest and conviction rates for violent offenders and sex offenders
      were 24.6% and 13.8% respectively, overall failure on release resulting in
      reincarceration was 41.5% and 18.5% respectively. The results showed no
      relationship between the CSS and recidivism or release failure. Implications for
      clinical use among this population of offenders are discussed.

PMID- 9169396
TI  - Risk of testicular cancer in cohort of boys with cryptorchidism.
AB  - OBJECTIVE: To determine the risk of testicular cancer in relation to undescended
      testis and its treatment based on recorded details of the maldescent, treatment,
      and biopsy from case notes. DESIGN: Cohort study. SETTING: Hospital for Sick
      Children, Great Ormond Street, London. SUBJECTS: 1075 boys with cryptorchidism
      treated by orchidopexy or hormones at the hospital during 1951-64. MAIN OUTCOME
      MEASURES: Relative risk of testicular cancer in the cohort compared with men in
      the general population. RESULTS: 12 testicular cancers occurred in 11 of the
      patients during follow up to mid-1990 (relative risk of cancer in males with
      cryptorchidism = 7.5 (95% confidence interval 3.9 to 12.8)). The relative risk
      fell significantly beyond 15 years after orchidopexy but did not decrease with
      younger age at orchidopexy. Risk was significantly raised in testes that had had
      biopsy samples removed during orchidopexy (relative risk = 66.7 (23.9 to 143.3)
      compared with a testis in a man in the general population) and was significantly
      greater in these testes than in undescended testes that had not had biopsy
      samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or
      distinguishing clinical aspects of the testes that had had biopsy samples taken
      and later developed malignancies were evident in the case notes. No histological
      abnormalities were evident at initial biopsy except in one testis that had
      features of dysgenesis. CONCLUSIONS: Biopsy seems to be a stronger risk factor
      for testicular cancer than any factor previously identified. The trauma of open
      biopsy may contribute substantially to risk of malignancy or the testes may have
      been selected for biopsy on the basis of clinical factors predictive of
      malignancy but not mentioned in the case notes.

PMID- 9169397
TI  - Prospective randomised study of intensive insulin treatment on long term survival
      after acute myocardial infarction in patients with diabetes mellitus. DIGAMI
      (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction)
      Study Group.
AB  - OBJECTIVES: To test the hypothesis that intensive metabolic treatment with
      insulin-glucose infusion followed by multidose insulin treatment in patients with
      diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN:
      Patients with diabetes mellitus and acute myocardial infarction were randomly
      allocated standard treatment plus insulin-glucose infusion for at least 24 hours
      followed by multidose insulin treatment or standard treatment (controls).
      SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin
      treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause
      mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There
      were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in
      the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P
      = 0.011). The effect was most pronounced among the predefined group that included
      272 patients without previous insulin treatment and at a low cardiovascular risk
      (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed
      by intensive subcutaneous insulin in diabetic patients with acute myocardial
      infarction improves long term survival, and the effect seen at one year continues
      for at least 3.5 years, with an absolute reduction in mortality of 11%. This
      means that one life was saved for nine treated patients. The effect was most
      apparent in patients who had not previously received insulin treatment and who
      were at a low cardiovascular risk.

PMID- 9169398
TI  - Case-control study of sudden infant death syndrome in Scotland, 1992-5.
AB  - OBJECTIVE: To investigate the relation between routine infant care practices and
      the sudden infant death syndrome in Scotland. METHODS: National study of 201
      infants dying of the sudden infant death syndrome (cases) and 276 controls by
      means of home interviews comparing methods of infant care and socioeconomic
      factors. RESULTS: Sleeping prone (odds ratio 6.96 (95% confidence interval 1.51
      to 31.97) and drug treatment in the previous week (odds ratio 2.33 (1.10 to
      4.94)) were more common in the cases than controls on multivariate analysis.
      Smoking was confirmed as a significant risk factor (odds ratio for mother and
      father both smoking 5.19 (2.26 to 11.91)). The risk increased with the number of
      parents smoking (P < 0.0001), with the number of cigarettes smoked by mother or
      father (P = 0.0001), and with bed sharing (P < 0.005). A new finding was an
      increased risk of dying of the syndrome for infants who slept at night on a
      mattress previously used by another infant or adult (odds ratio 2.51 (1.39 to
      4.52)). However, this increased risk was not established for mattresses totally
      covered by polyvinyl chloride. CONCLUSIONS: Sleeping prone and parental smoking
      are confirmed as modifiable risk factors for the sudden infant death syndrome.
      Sleeping on an old mattress may be important but needs confirmation before
      recommendations can be made.

PMID- 9169399
TI  - Reproductive pattern, perinatal mortality, and sex preference in rural Tamil
      Nadu, south India: community based, cross sectional study.
AB  - OBJECTIVES: To study reproductive pattern and perinatal mortality in rural Tamil
      Nadu, South India. DESIGN: Community based, cross sectional questionnaire study
      of 30 randomly selected areas served by health subcentres. SETTING: Rural parts
      of Salem District, Tamil Nadu, South India. SUBJECTS: 1321 women and their
      offspring delivered in the 6 months before the interview. MAIN OUTCOME MEASURES:
      Number of pregnancies, pregnancy outcome, spacing of pregnancies, sex of
      offspring, perinatal and neonatal mortality rates. RESULTS: 41% of the women
      (535) were primiparous; 7 women (0.5%) were grand multiparous (> 6 births). The
      women had a mean age of 22 years and a mean of 2.3 pregnancies and 1.8 live
      children. The sex ratio at birth of the index children was 107 boys per 100
      girls. The stillbirth rate was 13.5/1000 births, the neonatal mortality rate was
      35.3/1000, and the perinatal mortality rate was 42.0/1000. Girls had an excess
      neonatal mortality (rate ratio 3.42%; 95% confidence interval 1.68 to 6.98; this
      was most pronounced among girls born to multiparous women with no living sons
      (rate ratio 15.48 (2.04 to 177.73) v 1.87 (0.63 to 5.58) in multiparous women
      with at least one son alive). CONCLUSIONS: In this rural part of Tamil Nadu,
      women had a controlled reproductive pattern. The excess neonatal mortality among
      girls constitutes about one third of the perinatal mortality rate. It seems to be
      linked to a preference for sons and should therefore be addressed through a
      holistic societal approach rather than through specific healthcare measures.

PMID- 9169400
TI  - Population based study of prevalence of islet cell autoantibodies in monozygotic
      and dizygotic Danish twin pairs with insulin dependent diabetes mellitus.
AB  - OBJECTIVE: To study the comparative importance of environment and genes in the
      development of islet cell autoimmunity associated with insulin dependent diabetes
      mellitus. DESIGN: Population based study of diabetic twins. SETTING: Danish
      population. SUBJECTS: 18 monozygotic and 36 dizygotic twin pairs with one or both
      partners having insulin dependent diabetes. MAIN OUTCOME MEASURES: Presence of
      islet cell antibodies, insulin autoantibodies, and autoantibodies to glutamic
      acid decarboxylase (GAD65) in serum samples from twin pairs 10 years (range 0-30
      years) and 9.5 years (2-30 years) after onset of disease. RESULTS: In those with
      diabetes the prevalence of islet cell antibodies, insulin autoantibodies, and
      autoantibodies to glutamic acid decarboxylase in the 26 monozygotic twins was
      38%, 85%, and 92%, respectively, and in the dizygotic twins was 57%, 70%, and
      57%, respectively. In those without diabetes the proportions were 20%, 50%, and
      40% in the 10 monozygotic twins and 26%, 49%, and 40% in the 35 dizygotic twins.
      CONCLUSION: There is no difference between the prevalence of islet cell
      autoantibodies in dizygotic and monozygotic twins without diabetes, suggesting
      that islet cell autoimmunity is environmentally rather than genetically
      determined. Furthermore, the prevalence of islet cell antibodies was higher in
      the non-diabetic twins than in other first degree relatives of patients with
      insulin dependent diabetes. This implies that the prenatal or early postnatal
      period during which twins are exposed to the same environment, in contrast with
      that experienced by first degree relatives, is of aetiological importance.

PMID- 9169401
TI  - Doctors and patients don't agree: cross sectional study of patients' and doctors'
      perceptions and assessments of disability in multiple sclerosis.
AB  - OBJECTIVES: To compare the judgments of clinicians on which domains of health in
      the short form questionnaire (SF-36) would be most important to patients with
      multiple sclerosis with the opinions of patients themselves; to compare
      assessment of physical disability in multiple sclerosis by a clinician using
      Kurtzke's expanded disability status scale and a non-clinically qualified
      assistant using the Office of Population Census and Surveys' (OPCS) disability
      scale with self assessment of disability and other domains of health related
      quality of life by patients using the SF-36 and the EuroQol questionnaire; and to
      compare the scores of patients for each domain of the SF-36 with control data
      matched for age and sex. DESIGN: Cross sectional study. SETTING: Clinical
      department of neurology, Edinburgh. SUBJECTS: 42 consecutive patients with
      multiple sclerosis attending a neurology outpatient clinic for review or a
      neurology ward for rehabilitation. MAIN OUTCOME MEASURES: Scores on the SF-36;
      EuroQol; Kurtzke's expanded disability status scale; the OPCS disability scale.
      RESULTS: Patients and clinicians disagreed on which domains of health status were
      most important (chi 2 = 21, df = 7, P = 0.003). Patients' assessment of their
      physical disability using the physical functioning domain of the SF-36 was highly
      correlated with the clinicians' assessment (r = -0.87, P < 0.001) and the non
      clinical assessment (r = -0.90, P < 0.001). However, none of the measures of
      physical disability correlated with overall health related quality of life
      measured with EuroQol, Quality of life correlated with vitality, general health,
      and mental health in the SF-36, each of which patients rated as more important
      than clinicians and for each of which patients scored lower than the controls.
      CONCLUSIONS: Patients with multiple sclerosis and possibly those with other
      chronic diseases are less concerned than their clinicians about physical
      disability in their illness. Clinical trials in multiple sclerosis should assess
      the effect of treatment on the other elements of health status that patients
      consider important, which are also affected by the disease process, are more
      closely related to overall health related quality of life, and may well be
      adversely affected by side effects of treatment.

PMID- 9169402
TI  - Influence of cholesterol on survival after stroke: retrospective study.
AB  - OBJECTIVE: To investigate the association between serum cholesterol concentration
      and cerebrovascular disease. DESIGN: Retrospective study. SETTING: Acute stroke
      unit of inner city general hospital. SUBJECTS: 977 patients with acute stroke.
      MAIN OUTCOME MEASURES: Serum total cholesterol concentration, type of stroke
      investigated by computed tomography or magnetic resonance imaging, three month
      outcome (good (alive at home) or bad (dead or in care)), long term mortality.
      RESULTS: After adjustment for known prognostic factors, higher serum cholesterol
      concentrations were associated with reduced long term mortality after stroke
      (relative hazard 0.91 (95% confidence interval 0.84 to 0.98) per mmol/l increase
      in cholesterol) independently of stroke type, vascular territory and extent, age,
      and hyperglycaemia. Three month outcome was also influenced independently by
      serum cholesterol (P = 0.024). CONCLUSIONS: Our data suggest an association
      between poor stroke outcome and lower serum cholesterol concentration. Until a
      prospective controlled study has confirmed the benefits of lowering cholesterol
      concentration in elderly subjects, the application of cholesterol lowering
      guidelines cannot be justified as secondary prevention of acute stroke.

PMID- 9169403
TI  - Review by a local medical research ethics committee of the conduct of approved
      research projects, by examination of patients' case notes, consent forms, and
      research records and by interview.
AB  - OBJECTIVE: To monitor the conduct of medical research projects that have already
      been approved by the local medical research ethics committee. DESIGN: Follow up
      study of ethically approved studies (randomly selected from all the studies
      approved in the previous year) by examination of patients' case notes, consent
      forms, and research records and by interview of the researchers at their
      workplace. SETTING: Tayside, Scotland (mixed rural and urban population).
      SUBJECTS: 30 research projects approved by Tayside local medical research ethics
      committee. MAIN OUTCOME MEASURES: Adherence to the agreed protocol, particularly
      for recruitment (obtaining and recording informed consent) and for specific
      requirements of the ethics committee, including notification of changes to the
      protocol and of adverse events. RESULTS: In one project only oral consent had
      been obtained, and in a quarter of the studies one or more consent forms were
      incorrectly completed. Inadequate filing of case notes in five studies and of
      consent forms in six made them unavailable for scrutiny. Adverse events were
      reported, but there was a general failure to report the abandoning or non
      starting of projects in two studies the investigators failed to notify a change
      in the responsible researcher. CONCLUSIONS: Monitoring of medical research by
      local medical research ethics committees promotes and preserves ethical
      standards, protects subjects and researchers, discourages fraud, and has the
      support of investigators. We recommend that 10% of projects should undergo on
      site review, with all others monitored by questionnaire. This would require about
      six person hours of time and a salary bill of 120 pounds per study monitored.

PMID- 9169404
TI  - Redox regulation of the DNA binding activity in transcription factor PEBP2. The
      roles of two conserved cysteine residues.
AB  - Transcription factor PEBP2/CBF consists of a DNA binding subunit, alpha, and a
      regulatory subunit, beta. The alpha subunit has an evolutionarily conserved 128
      amino acid region termed "Runt domain" that is responsible for both DNA binding
      and heterodimerization with the beta subunit. The Runt domain in all mammalian
      submembers of the alpha subunit contains two conserved cysteine residues, and its
      DNA binding activity undergoes redox regulation. To investigate the mechanism of
      this redox regulation, we performed site-directed mutagenesis of the two
      conserved cysteines in the Runt domain of the mouse PEBP2alphaA homolog.
      Substitution of Cys-115 to serine resulted in a partially impaired DNA binding,
      which remained highly sensitive to a thiol-oxidizing reagent, diamide.
      Conversely, the corresponding substitution of Cys-124 caused an increased DNA
      binding concomitant with an increased resistance to diamide. In contrast,
      substitution of either cysteine to aspartate was destructive to DNA binding to
      marked extents. These results have revealed that both Cys-115 and Cys-124 are
      responsible for the redox regulation in their own ways with low and high
      oxidizabilities, respectively. We have also found that two cellular thiol
      reactive proteins, thioredoxin and Ref-1, work effectively and synergistically
      for activation of the Runt domain. Interestingly, the beta subunit further
      enhanced the activation by these proteins and reciprocally prevented the
      oxidative inactivation by diamide. These findings collectively suggest the
      possibility that the Runt domain's function in vivo could be dynamically
      regulated by the redox mechanism with Trx, Ref-1, and the beta subunit as key
      modulators.

PMID- 9169405
TI  - Induction of cytosolic phospholipase A2 by oncogenic Ras in human non-small cell
      lung cancer.
AB  - Mutations in Ras family members that confer oncogenic potential are frequently
      observed in specific human cancers. We report that human non-small cell lung
      cancer (NSCLC) lines that harbor oncogenic mutations in Ki-Ras (H460, A549,
      H2122) synthesized high levels of prostaglandin E2 (PGE2) compared with NSCLC
      lacking Ras mutations or non-transformed lung epithelial cells (BEAS-2B). This
      increased PGE2 production was mediated by constitutively high expression of 85
      kDa cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2). The
      increased expression of cPLA2 protein was mediated through elevated mRNA levels
      and activation of the cPLA2 promoter. Induction of cPLA2 promoter activity was
      blocked by expression of dominant-negative forms of Ras. Inhibition of Ras by the
      farnesyltransferase inhibitor BZA-5B inhibited prostaglandin synthesis in H2122
      cells by decreasing expression of both cPLA2 and COX-2. Finally, inhibitors of
      eicosanoid synthesis blocked anchorage-independent growth of NSCLC lines
      exhibiting Ki-Ras mutations. These results identify cPLA2 as a novel Ras
      inducible regulator of eicosanoid synthesis that participates in cellular
      transformation.

PMID- 9169406
TI  - Developmental regulation of presenilin-1 processing in the brain suggests a role
      in neuronal differentiation.
AB  - Most cases of early-onset familial Alzheimer's disease are caused by mutations in
      the presenilin genes. Presenilin-1 (PS1) is subject to proteolytic cleavage
      resulting in the accumulation of N- and C-terminal fragments. In this report, we
      show that the proteolytic cleavage of PS1 is developmentally regulated in the
      brain. Low levels of full-length PS1 and higher levels of 30-kDa N-terminal and
      20-kDa C-terminal fragments are identified at all developmental stages in the rat
      brain. However, in the adult brain, additional 36-kDa N-terminal and 14-kDa C
      terminal fragments appear and become major PS1 species. Alternative N-terminal
      PS1 fragments also appear in the adult human brain, but are more heterogenous
      than in the rat brain. The alternative PS1 fragments are not detected at
      significant levels in rat or human peripheral tissues that express PS1. The
      alternative cleavage of PS1 is also detected in primary cultures of rat
      hippocampal neurons, but not in astrocytes, and is induced by neuronal
      differentiation. Furthermore, alternative PS1 cleavage is detected in rat PC12
      cells and human neuroblastoma SH-SY5Y cells following induction of neuronal
      differentiation. These results suggest that an alternative pathway of PS1
      proteolytic processing is induced in the brain by neuronal differentiation. PS1
      may therefore play an important role in brain development and neuronal function,
      which may relate to the brain-specific pathological effects of PS1 mutations.

PMID- 9169407
TI  - Molecular characterization of a 20.8-kDa Schistosoma mansoni antigen. Sequence
      similarity to tegumental associated antigens and dynein light chains.
AB  - Survival of Schistosoma mansoni within the infected host requires the parasite to
      actively maintain its protective tegument. The components responsible for this
      maintenance are therefore attractive targets for immunoprophylaxis or
      chemotherapy. Here we report the molecular characterization of a 20.8-kDa
      tegumental antigen with sequence similarity to dynein light chains and tegumental
      associated antigens. A cDNA encoding the 20.8-kDa polypeptide contains an open
      reading frame of 181 amino acids and predicts an isoelectric point of 7.27.
      Expression of the 20.8-kDa antigen is developmentally regulated, with the highest
      concentration found in cercariae. Our data show that the 20.8-kDa polypeptide
      specifically interacts with a S. mansoni 10.4-kDa dynein light chain that we have
      previously described (Hoffmann, K. F., and Strand, M. (1996) J. Biol. Chem. 271,
      26117-26123). Velocity sedimentation analysis of a parasite extract demonstrated
      that this 10.4-kDa dynein light chain and the 20.8-kDa polypeptide were present
      in a complex that sedimented at 4.4 Svedberg units. We have also shown by
      antibody cross-reactivity that a 20.8-kDa homolog of the S. mansoni antigen is
      present in Schistosoma japonicum, but not in Schistosoma hematobium or Fasciola
      hepatica. Because the 20.8-kDa polypeptide displays ideal characteristics of a
      potential vaccine candidate, including (i) expression in the tegument, (ii)
      significant divergence from mammalian brain cytoplasmic dynein, and (iii) a
      conserved homolog in S. japonicum, we are currently evaluating its
      immunoprophylactic efficacy.

PMID- 9169408
TI  - Interactions of the amino-terminal noncollagenous (NC1) domain of type VII
      collagen with extracellular matrix components. A potential role in epidermal
      dermal adherence in human skin.
AB  - Type VII collagen, the major component of anchoring fibrils, consists of a
      central collagenous triple-helical domain flanked by two noncollagenous domains,
      NC1 and NC2. The NC1 domain contains multiple submodules with homology to known
      adhesive molecules including fibronectin type III-like repeats and the A domain
      of von Willebrand factor. In this study, we produced the entire NC1 domain of
      human type VII collagen in the stably transfected human kidney 293 cell clones
      and purified large quantities of the recombinant NC1 protein from serum-free
      culture media. The recombinant NC1 formed interchain disulfide-bonded dimers and
      trimers and was N-linked glycosylated. Tunicamycin inhibited the cellular
      secretion of NC1, suggesting that N-linked glycosylation may play a role in NC1
      secretion. The recombinant NC1 was indistinguishable from the authentic NC1
      obtained from human amnions or WISH cells with respect to N-linked sugar content,
      electrophoretic mobility, rotary shadow imaging, and binding affinity to type IV
      collagen. Purified recombinant NC1, like authentic NC1, also bound specifically
      to fibronectin, collagen type I, and a laminin 5/6 complex. Both monomeric and
      trimeric forms of NC1 exhibited equal affinity for these extracellular matrix
      components, suggesting that the individual arms of NC1 can function
      independently. The multiple interactions of NC1 with other extracellular matrix
      components may support epidermal-dermal adhesion.

PMID- 9169409
TI  - Inhibition of HIV-1 replication using a mutated tRNALys-3 primer.
AB  - Cellular tRNALys-3 serves as the primer for reverse transcription of human
      immunodeficiency virus, type 1 (HIV-1). tRNALys-3 interacts directly with HIV-1
      reverse transcriptase, is packaged into viral particles and anneals to the primer
      binding site (PBS) of the HIV-1 genome to initiate reverse transcription.
      Therefore, the priming step of reverse transcription is a potential target for
      antiviral strategies. We have developed a mutant tRNALys-3 derivative with
      mutations in the PBS-binding region such that priming specificity was re-directed
      to the highly conserved TAR stem-loop region. This mutant tRNA retains high
      affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able
      to prime at both the targeted TAR sequence and at the viral PBS. Constitutive
      expression of mutant tRNA in T-cells results in marked inhibition of HIV-1
      replication, as determined by measurements of viral infectivity, syncytium
      formation, and p24 production. Inhibition of retroviral replication through
      interference with the normal process of priming constitutes a new anti-retroviral
      approach and also provides a novel tool for dissecting molecular aspects of
      priming.

PMID- 9169410
TI  - Cytotoxicity and apoptosis produced by arachidonic acid in Hep G2 cells
      overexpressing human cytochrome P4502E1.
AB  - The goal of the current study was to evaluate the effects of arachidonic acid, as
      a representative polyunsaturated fatty acid, on the viability of a Hep G2 cell
      line, which has been transduced to express human cytochrome P4502E1 (CYP2E1).
      Arachidonic acid produced a concentration- and time-dependent toxicity to Hep G2
      MV2E1-9 cells, which express CYP2E1, but little or no toxicity was found with
      control Hep G2-MV-5 cells, which were infected with retrovirus lacking human
      CYP2E1 cDNA. In contrast to arachidonic acid, oleic acid was not toxic to the Hep
      G2-MV2E1-9 cells. The cytotoxicity of arachidonic acid appeared to involve a
      lipid peroxidation type of mechanism since toxicity was enhanced after depletion
      of cellular glutathione; formation of malondialdehyde and 4-hydroxy-2-nonenal was
      markedly elevated in the cells expressing CYP2E1, and toxicity was prevented by
      antioxidants such as alpha-tocopherol phosphate, 6-hydroxy-2,5,7,8
      tetramethylchroman-2-carboxylic acid (trolox), propylgallate, ascorbate, and
      diphenylphenylenediamine, and the iron chelator desferrioxamine. Transfection of
      the Hep G2-MV2E1-9 cells with plasmid containing CYP2E1 in the sense orientation
      enhanced the arachidonic acid toxicity, whereas transfection with plasmid
      containing CYP2E1 in the antisense orientation decreased toxicity. The CYP2E1
      dependent arachidonic acid toxicity appeared to involve apoptosis, as
      demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP nick end
      labeling and DNA laddering experiments. Trolox, which prevented toxicity of
      arachidonic acid, also prevented the apoptosis. Transfection with a plasmid
      containing bcl-2 resulted in complete protection against the CYP2E1-dependent
      arachidonic acid toxicity. It is proposed that elevated production of reactive
      oxygen intermediates by cells expressing CYP2E1 can cause lipid peroxidation,
      which subsequently promotes apoptosis and cell toxicity when the cells are
      enriched with polyunsaturated fatty acids such as arachidonic acid. The Hep G2
      MV2E1-9 cells appear to be a valuable model to study interaction between CYP2E1,
      polyunsaturated fatty acids, reactive radicals, and the consequence of these
      interactions on cell viability and to reproduce several of the key features
      associated with ethanol hepatotoxicity in the intragastric infusion model of
      ethanol treatment.

PMID- 9169411
TI  - Insulin stimulates guanine nucleotide exchange on Rab4 via a wortmannin-sensitive
      signaling pathway in rat adipocytes.
AB  - Rab4, a member of the Rab family of Ras-related small GTP-binding proteins, has
      been shown to be associated with GLUT4-containing vesicles and implicated in the
      insulin action on glucose transport in rat adipocytes. In the present study, we
      investigated the insulin effects on the guanine nucleotide exchange on Rab4. In
      electrically permeabilized rat adipocytes, the amount of [35S]guanosine 5'-O-(3
      thiotrisphosphate) (GTPgammaS) bound to Rab4 increased in a time-dependent manner
      during 45 min of the incubation period. Addition of insulin resulted in about a 2
      fold stimulation of the binding of [35S]GTPgammaS to Rab4, indicating that
      insulin stimulated the guanine nucleotide exchange on the GTPase. Pretreatment of
      the cells with wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase,
      completely abolished the stimulatory effect of insulin on [35S]GTPgammaS binding
      to Rab4. Wortmannin also attenuated the nucleotide binding to Rab4 in the basal
      cells, suggesting that phosphatidylinositol 3-kinase activity may be essential
      for regulation of guanine nucleotide exchange on the GTPase and insulin may up
      regulate the exchange activity by stimulating the lipid kinase. Insulin-induced
      subcellular redistribution of Rab4 from the microsomal fraction to the soluble
      fraction was also inhibited by wortmannin. These results suggest that insulin
      stimulates the guanine nucleotide exchange on Rab4 via a phosphatidylinositol 3
      kinase-dependent signaling pathway and that Rab4 is one of possible targets of
      insulin action on intracellular vesicle traffic in rat adipocytes.

PMID- 9169412
TI  - Identification and sequence analysis of contact sites between ribosomal proteins
      and rRNA in Escherichia coli 30 S subunits by a new approach using matrix
      assisted laser desorption/ionization-mass spectrometry combined with N-terminal
      microsequencing.
AB  - Cross-linked peptide-oligoribonucleotide complexes derived from distinct regions
      of the rRNA and individual ribosomal proteins of the 30 S ribosomal subunits from
      Escherichia coli were isolated and purified. Cross-linking sites at the amino
      acid and nucleotide level were determined by N-terminal amino acid sequence
      analysis in combination with matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS). MALDI-MS analysis performed subsequent to a partial
      alkaline hydrolysis of cross-linked peptide-oligoribonucleotide complexes allowed
      for the first time the cross-linked rRNA moiety to be sequenced by this
      technique. In this manner Lys-44 in S4 was determined to be cross-linked to the
      oligoribonucleotide at positions 1531-1542 on the 16 S RNA (whereby either U-1541
      or A-1542 is the actual cross-link site), Lys-75 in S7 to positions 1374-1379 (C
      1378 cross-linked), Met-114 in S7 to 1234-1241 (U-1240 cross-linked), Lys-55 in
      S8 to 651-654 (U-653 cross-linked), and Lys-29 in S17 to 629-633 (U-632 cross
      linked). The novel approach applied here promises to be useful for similar
      studies on other known protein.RNA complexes.

PMID- 9169413
TI  - Reconstitution of alpha2D-adrenergic receptor coupling to phospholipase D in a
      PC12 cell lysate.
AB  - We have previously shown that alpha2-adrenergic receptor-mediated coupling to
      phospholipase D (PLD) in vascular tissues requires a tyrosine kinase activity
      (Jinsi, A., Paradise, J., and Deth, R. C. (1996) Eur. J. Pharmacol. 302, 183
      190). To further clarify this mode of regulation we reconstituted alpha2A/D
      adrenergic receptor-stimulated PLD activity in PC12 cells expressing the cloned
      receptor. [3H]Myristic acid-labeled cells were lysed by nitrogen cavitation, and
      aliquots of subnuclear fraction were utilized in the PLD assay. Agonist
      stimulated PLD activity was measured in the presence of 0.4% butanol as
      [3H]phosphatidylbutanol formation. Both GTP and its non-hydrolyzable analog
      guanosine 5'-O-(thiotriphosphate) stimulated PLD activity in a concentration- and
      time-dependent manner that required co-activation of protein kinase C by phorbol
      dibutyrate. Addition of epinephrine produced a 3-fold stimulation of PLD activity
      in the presence of GTP and GDP. This agonist-stimulated PLD activity was
      completely blocked by the alpha2-adrenergic receptor antagonist rauwolscine and
      by Clostridium botulinum toxin as well as by antibodies directed against either
      pp60(src), RhoA, or Ras GTPase-activating protein. These results indicate that
      coupling of the alpha2A/D-adrenergic receptor to PLD is complexly regulated by
      both the tyrosine kinase pp60(src) and the low molecular weight G protein RhoA.

PMID- 9169414
TI  - Characterization of Lnk. An adaptor protein expressed in lymphocytes.
AB  - Stimulation of the T cell antigen receptor (TCR) activates a set of non-receptor
      protein tyrosine kinases that assist in delivering signals to the cell interior.
      Among the presumed substrates for these kinases, adaptor proteins, which
      juxtapose effector enzyme systems with the antigen receptor complex, figure
      prominently. Previous studies suggested that Lnk, a 38-kDa protein consisting of
      a single SH2 domain and a region containing potential tyrosine phosphorylation
      sites, might serve to join Grb2, phospholipase C-gamma1, and phosphatidylinositol
      3-kinase to the TCR. To elucidate the physiological roles of Lnk in T cell signal
      transduction, we isolated the mouse Lnk cDNA, characterized the structure of the
      mouse Lnk gene, and generated transgenic mice that overproduce Lnk in thymocytes.
      Here we report that although Lnk becomes phosphorylated during T cell activation,
      it plays no limiting role in the TCR signaling process. Moreover, we have
      distinguished p38(Lnk) from the more prominent 36-kDa tyrosine phosphoproteins
      that appear in activated T cells. Together these studies suggest that Lnk
      participates in signaling from receptors other than antigen receptors in
      lymphocytes.

PMID- 9169415
TI  - The carboxyl-terminal region of STAT3 controls gene induction by the mouse
      haptoglobin promoter.
AB  - Haptoglobin (HP) is one of the major acute phase plasma proteins in the mouse,
      and its synthesis is additively induced by interleukin (IL)-6 and
      glucocorticoids. STAT3 serves as the mediator of the IL-6 receptor signal and
      appears to contribute to the transcriptional induction of acute phase protein
      genes. The carboxyl-terminal region of STAT3, consisting of an acidic domain and
      containing a serine phosphorylation site, has been proposed to contribute to the
      induction process. To assess the role of STAT3 in the transcriptional control of
      the HP promoter, we applied two mutant forms of STAT3: one with a deletion of the
      carboxyl-terminal 55 amino acid residues, STAT3Delta55C, and the other with a
      substitution of serine 727 to alanine, STAT3SA. Like the wild-type STAT3, both
      mutant STAT3 forms are activated by the signal-transducing subunit of the IL-6
      receptor, gp130, or by co-transfected IL-3 receptor. Ectopic expression and
      activation of wild-type STAT3 or STAT3SA in HepG2 hepatoma cells similarly
      enhance transcription through the IL-6-response element of the HP promoter. This
      enhancement is specific for STAT3 and cannot be reproduced by STAT1 or STAT5. In
      contrast, STAT3Delta55C inhibits IL-6-induced transcriptional activation.
      Interestingly, whereas receptor-activated STAT3 also enhances stimulation of the
      haptoglobin promoter by dexamethasone through the glucocorticoid receptor,
      activated STAT3Delta55C reduces the regulation below the level achieved by the
      glucocorticoid receptor alone. This transdominant action by STAT3Delta55C is
      dependent on a functional IL-6-responsive element. The data suggest that the
      carboxyl-terminal domain, but not its serine phosphorylation site of STAT3, is
      required for transcription as part of the hematopoietin receptor signaling as
      well as for cooperation with other transcription factors such as the
      glucocorticoid receptor.

PMID- 9169416
TI  - Variants of tissue-type plasminogen activator that display extraordinary
      resistance to inhibition by the serpin plasminogen activator inhibitor type 1.
AB  - Fibrinolysis is regulated in part by the interaction of tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous
      investigations suggest that three specific arginine residues, Arg-298, Arg-299,
      and Arg-304 of t-PA, play a critical role in this important regulatory
      interaction. Our earlier studies have demonstrated that conversion of any of
      these three residues to a glutamic acid residue reduced the rate of inhibition of
      t-PA by PAI-1 by factors varying from 58-64. In addition, we have reported that
      the second order rate constant for inhibition by PAI-1 of the variant t
      PA/K296E,R298E,R299E is reduced by a factor of approximately 2800 compared with
      that of wild type t-PA. In this study, we have significantly extended our earlier
      observations by identifying t-PA variants that are substantially more resistant
      to inhibition by PAI-1 than any previously reported variants of t-PA or urokinase
      type plasminogen activator. Single-chain t-PA/R275E,R298E, R299E,R304E, for
      example, is inhibited by PAI-1 approximately 120, 000 times less rapidly than
      single-chain, wild type t-PA. We also report the first direct comparison of the
      effects of charge reversal mutations of Arg-298, Arg-299, and/or Arg-304 on the
      properties of the single- and two-chain forms of t-PA. While these mutations
      confer extraordinary resistance to inhibition by PAI-1 to both forms of the
      enzyme, our observations reveal that the single-chain enzyme is affected to a
      greater extent than the two-chain enzyme. Two-chain, wild type t-PA is inhibited
      by PAI-1 approximately 1.4 times more rapidly than single-chain t-PA. The
      corresponding ratio increases to 7.6 or 6.7, respectively, for variants of t-PA
      containing the R298E, R299E or R298E,R299E,R304E mutations.

PMID- 9169417
TI  - Evidence for the direct involvement of transmembrane region 6 of the
      lutropin/choriogonadotropin receptor in activating Gs.
AB  - The luteinizing hormone/chorionic gonadotropin receptor (LHR) is a heptahelical
      receptor that interacts primarily with Gs. Previous studies by others have shown
      that some forms of familial male precocious puberty are associated with mutations
      of the human LHR in the sixth transmembrane region that result in constitutive
      activation of the receptor. This study demonstrates that a peptide corresponding
      to the lower portion of the sixth transmembrane region of the LHR can
      significantly activate adenylyl cyclase activity. Experiments with membranes
      derived from wild-type versus cyc- S49 cells demonstrate that the stimulation of
      cyclase by this peptide is due to an activation of Gs. As such, our data
      demonstrate a direct role for transmembrane region 6 of the rat LHR in activating
      Gs and therefore raise the possibility that mutations in transmembrane region 6
      of the LHR may directly affect the coupling of the receptor to Gs. Significantly,
      these data are the first to demonstrate the ability of a transmembrane portion of
      a G protein-coupled receptor, in the absence of any contributions from an
      intracellular loop region, to activate a G protein.

PMID- 9169418
TI  - Mutations in the 1,25-dihydroxyvitamin D3 receptor identifying C-terminal amino
      acids required for transcriptional activation that are functionally dissociated
      from hormone binding, heterodimeric DNA binding, and interaction with basal
      transcription factor IIB, in vitro.
AB  - To investigate a potential ligand-dependent transcriptional activation domain (AF
      2) in the C-terminal region of the human vitamin D receptor (hVDR), two conserved
      residues, Leu-417 and Glu-420, were replaced with alanines by site-directed
      mutagenesis (L417A and E420A). Transcriptional activation in response to 1, 25
      dihydroxyvitamin D3 (1,25-(OH)2D3) was virtually eliminated when either point
      mutant was transfected into several mammalian cell lines. Furthermore, both
      mutants exhibited a dominant negative phenotype when expressed in COS-7 cells.
      Scatchard analysis at 4 degrees C and a ligand-dependent DNA binding assay at 25
      degrees C revealed essentially normal 1,25-(OH)2D3 binding for the mutant hVDRs,
      which were also equivalent to native receptor in associating with the rat
      osteocalcin vitamin D responsive element as a presumed heterodimer with retinoid
      X receptor. Glutathione S-transferase-human transcription factor IIB (TFIIB)
      fusion protein linked to Sepharose equally coprecipitated the wild-type hVDR and
      the AF-2 mutants. These data implicate amino acids Leu-417 and Glu-420, residing
      in a putative alpha-helical region at the extreme C terminus of hVDR, as critical
      in the mechanism of 1, 25-(OH)2D3-stimulated transcription, likely mediating an
      interaction with a coactivator(s) or a component of the basal transcriptional
      machinery distinct from TFIIB.

PMID- 9169419
TI  - Reversible calcium-dependent interaction of liposomes with pulmonary surfactant
      protein A. Analysis by resonant mirror technique and near-infrared light
      scattering.
AB  - Surfactant protein A (SP-A) is crucial for lung function, including tubular
      myelin formation and lipid uptake by type II pneumocytes. Known properties of SP
      A in vitro are its Ca2+-dependent interaction with phospholipids and its role in
      the aggregation of liposomes. To dissect and to analyze these processes, we have
      immobilized SP-A and measured binding of liposomes by the resonant mirror
      technique. Liposome aggregation was followed separately by kinetic light
      scattering in suspensions. It was found that SP-A-mediated binding and
      aggregation of liposomes have a common K0.5 of 20 microM for free Ca2+,
      independent of the species (sheep, rat, or cow) and of the phospholipid
      composition, and that both reactions exhibit the same high cooperativity (Hill
      coefficients of 6-9) for Ca2+ ions. However, binding of liposomes to SP-A is >10
      fold faster than aggregation. Both processes are completely reversed by low Ca2+
      concentrations, but liposomes dissociate from SP-A in <0.3 s, whereas
      disaggregation of the liposomes takes approximately 30 s. At equilibrium, the
      level of aggregation depends on the concentration of free SP-A. We interpret
      these results to be a rapid and reversible sequence of three reactions: (i) a
      cooperative Ca2+-dependent conformational change in SP-A, (ii) binding of Ca2+
      bound SP-A to liposomes, and (iii) aggregation of the Ca2+/SP-A-bound liposomes.

PMID- 9169420
TI  - p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110.
AB  - The mammalian phosphoinositide 3-kinases (PI3Ks) p110alpha, beta, and delta form
      heterodimers with Src homology 2 (SH2) domain-containing adaptors such as
      p85alpha or p55(PIK). The two SH2 domains of these adaptors bind to
      phosphotyrosine residues (pY) found within the consensus sequence pYXXM. Here we
      show that a heterodimer of the Drosophila PI3K, Dp110, with an adaptor, p60, can
      be purified from S2 cells with a pYXXM phosphopeptide affinity matrix. Using
      amino acid sequence from the gel-purified protein, the gene encoding p60 was
      cloned and mapped to the genomic region 21B8-C1, and the exon/intron structure
      was determined. p60 contains two SH2 domains and an inter-SH2 domain but lacks
      the SH3 and breakpoint cluster region homology (BH) domains found in mammalian
      p85alpha and beta. Analysis of the sequence of p60 shows that the amino acids
      responsible for the SH2 domain binding specificity in mammalian p85alpha are
      conserved and predicts that the inter-SH2 domain has a coiled-coil structure. The
      Dp110.p60 complex was immunoprecipitated with p60-specific antisera and shown to
      possess both lipid and protein kinase activity. The complex was found in larvae,
      pupae, and adults, consistent with p60 functioning as the adaptor for Dp110
      throughout the Drosophila life cycle.

PMID- 9169421
TI  - Identification of novel human WW domain-containing proteins by cloning of ligand
      targets.
AB  - A recently described protein module consisting of 35-40 semiconserved residues,
      termed the WW domain, has been identified in a number of diverse proteins
      including dystrophin and Yes-associated protein (YAP). Two putative ligands of
      YAP, termed WBP-1 and WBP-2, have been found previously to contain several short
      peptide regions consisting of PPPPY residues (PY motif) that mediate binding to
      the WW domain of YAP. Although the function(s) of the WW domain remain to be
      elucidated, these observations strongly support a role for the WW domain in
      protein-protein interactions. Here we report the isolation of three novel human
      cDNAs encoding a total of nine WW domains, using a newly developed approach
      termed COLT (cloning of ligand targets), in which the rapid cloning of modular
      protein domains is accomplished by screening cDNA expression libraries with
      specific peptide ligands. Two of the new genes identified appear to be members of
      a family of proteins, including Rsp5 and Nedd-4, which have ubiquitin-protein
      ligase activity. In addition, we demonstrate that peptides corresponding to PY
      and PY-like motifs present in several known signaling or regulatory proteins,
      including RasGAP, AP-2, p53BP-2 (p53-binding protein-2), interleukin-6 receptor
      alpha, chloride channel CLCN5, and epithelial sodium channel ENaC, can
      selectively bind to certain of these novel WW domains.

PMID- 9169422
TI  - Transforming growth factor-beta1 inhibits type I inositol 1,4,5-trisphosphate
      receptor expression and enhances its phosphorylation in mesangial cells.
AB  - A potentially important cross-talk characteristic of transforming growth factor
      beta (TGF-beta) is to inhibit platelet-derived growth factor-induced
      intracellular calcium rise (Baffy, G., Sharma, K., Shi, W., Ziyadeh, F. N., and
      Williamson, J. R. (1995) Biochem. Biophys. Res. Commun. 210, 378-383) in murine
      mesangial cells. The present study examined the possible basis for this effect by
      evaluating the regulation of the type I inositol 1,4,5-trisphosphate receptor
      (IP3R) by TGF-beta. TGF-beta1 down-regulates IP3R protein expression by >90% with
      maximal and half-maximal effects after 8 and 2 h, respectively. TGF-beta1 also
      decreased IP3R mRNA expression by 59% after 1 h. Phosphorylation of the IP3R was
      also demonstrated as early as 15 min after TGF-beta1 exposure. Back
      phosphorylation assays of IP3R from TGF-beta1-treated mesangial cells with
      protein kinase A (PKA), indicated that TGF-beta1-induced phosphorylation of the
      IP3R occurs at similar sites as for PKA. In vitro kinase assays using the known
      IP3R peptide substrates for PKA, RPSGRRESLTSFGNP and ARRDSVLAAS, demonstrated
      that TGF-beta1 induces phosphorylation of both peptides (158 and 123% of control
      values, respectively). TGF-beta1-induced phosphorylation was prevented by the
      addition of the PKA inhibitor peptide in the in vitro kinase assay. It is
      proposed that TGF-beta-mediated effects on the IP3R may be an important
      characteristic of its ability to modulate the response of cells to factors that
      employ IP3R-mediated calcium release.

PMID- 9169423
TI  - Interaction of the erythrocyte lactate transporter (monocarboxylate transporter
      1) with an integral 70-kDa membrane glycoprotein of the immunoglobulin
      superfamily.
AB  - Treatment of intact erythrocytes with 4,4'-diisothiocyanostilbene-2, 2'
      disulfonate (DIDS) causes irreversible inhibition and chemical labeling of the
      lactate transporter, monocarboxylate transporter 1 (MCT1) (Poole, R. C., and
      Halestrap, A. P. (1992) Biochem. J. 283, 855-862). In rat erythrocytes DIDS also
      causes cross-linking of MCT1 to another protein in the membrane to give a product
      of 130 kDa on SDS-polyacrylamide gel electrophoresis. Cross-linking is markedly
      reduced by those compounds that protect against irreversible inhibition of
      lactate transport by DIDS and enhanced by imposition of a pH gradient across the
      plasma membrane to recruit the substrate binding site of MCT1 to an exofacial
      conformation. These data indicate that DIDS cross-linking is via the same site on
      MCT1 as is responsible for inhibition of transport. Antibodies raised against the
      cross-linked conjugate react with proteins of approximately 40 kDa (MCT1) and 70
      kDa on Western blots of erythrocyte membranes and an additional band of 130 kDa
      after treatment of erythrocytes with 100 microM DIDS. The 70-kDa protein that is
      cross-linked to MCT1 was purified and shown to contain N-linked carbohydrate; the
      apparent core molecular mass is 40 kDa. Amino acid sequencing showed that the
      protein is the rat equivalent of the membrane-spanning mouse teratocarcinoma
      glycoprotein GP-70, a member of the immunoglobulin superfamily related to basigin
      (Ozawa, M., Huang, R. P., Furukawa, T. , and Muramatsu, T. (1988) J. Biol. Chem.
      263, 3059-3062). Possible implications of the specific interaction between MCT1
      and this protein are discussed.

PMID- 9169424
TI  - Isolation of the SO4-4-GalNAcbeta1,4GlcNAcbeta1,2Manalpha-specific receptor from
      rat liver.
AB  - Glycoproteins, such as the glycoprotein hormone lutropin (LH), bear
      oligosaccharides terminating with the sequence SO4-4GalNAcbeta1,
      4GlcNAcbeta1,2Manalpha (S4GGnM) and are rapidly removed from the circulation by a
      receptor present in hepatic endothelial cells and Kupffer cells. Rapid removal
      from the circulation is essential for attaining maximal hormone activity in vivo.
      We have isolated a protein from rat liver which has the properties expected for
      the S4GGnM-specific receptor (S4GGnM-R). The S4GGnM-R is closely related to the
      macrophage mannose receptor (Man-R) both antigenically and structurally. At least
      12 peptides prepared from the S4GGnM-R have amino acid sequences that are
      identical to those of the Man-R. Nonetheless, the ligand binding properties of
      the S4GGnM-R and the Man-R differ in a number of respects. The S4GGnM-R binds to
      immobilized LH but not to immobilized mannose, whereas the Man-R binds to
      immobilized mannose but not to immobilized LH. When analyzed using a binding
      assay that precipitates receptor ligand complexes with polyethylene glycol, the
      S4GGnM-R is able to bind S4GGnM-bovine serum albumin (S4GGnM-BSA) conjugates
      whereas the Man-R is not. In contrast both the S4GGnM-R and the Man-R are able to
      bind Man-BSA. Monosaccharides that inhibit binding of Man-BSA by the Man-R
      enhance binding by the S4GGnM-R. Oligosaccharides terminating with S4GGnM and
      those terminating with Man are bound at independent sites on the S4GGnM-R. The
      S4GGnM-R present in hepatic endothelial cells may account for clearance of
      glycoproteins bearing oligosaccharides terminating with S4GGnM and glycoproteins
      bearing oligosaccharides terminating with either mannose, fucose, or N
      acetylglucosamine.

PMID- 9169425
TI  - Effects of intracellular tyrosine residue mutation and carboxyl terminus
      truncation on signal transduction and internalization of the rat bradykinin B2
      receptor.
AB  - Presently, little is known of the amino acid motif(s) participating in bradykinin
      B2 receptor-mediated signal transduction processes. In this report we investigate
      the potential role of the two existing tyrosine (Tyr) residues in the
      intracellular regions and the carboxyl terminus in the regulatory function of
      this receptor. Rat-1 cells, which do not contain detectable bradykinin B2
      receptor, were transfected with wild type and mutant receptor cDNAs. Tyr-131 and
      Tyr-321 were each mutated to corresponding alanine-, serine-, and phenylalanine
      containing sequences. The last 34 amino acid residues of the carboxyl terminus
      were truncated. Rat-1 cells transfected with the mutant forms of the receptor
      cDNA including the truncated COOH-terminal cDNA all bound [3H]bradykinin with
      essentially the same Kd of approximately 2.2 nM as cells transfected with the
      wild type bradykinin B2 receptor. However, mutating Tyr-131 resulted in important
      changes in bradykinin-stimulated phosphoinositide turnover and arachidonate
      release. For example, exchanging Tyr-131 for alanine led to an 80% decreased
      arachidonate release (p < 0.005), 90% decrease in inositol phosphate (IP)
      accumulation (p < 0.001), with receptor uptake at 15 min remaining essentially
      unchanged. Mutating the same Tyr to phenylalanine resulted in unchanged
      bradykinin-stimulated IP accumulation, only a slightly lowered arachidonate
      release, and unchanged receptor uptake at 15 min. Mutating Tyr-321 to alanine
      resulted in a very different pattern. There was a small but significant reduction
      in arachidonate release (p < 0.03) and IP accumulation (p < 0.008) with a large,
      30%, increase in receptor uptake at 15 min (p < 0.010). Truncation of a portion
      of the carboxyl tail also proved meaningful, with a 60% decrease in arachidonate
      release and an 80% decrease in IP accumulation. The truncation also resulted in a
      large, 130%, decrease in receptor uptake at 15 min (p < 0.023). Taken together,
      these results point to Tyr-131 as an important element in determining bradykinin
      stimulated arachidonate release and IP accumulation. Tyrosine phosphorylation at
      this site apparently does not play a major role. Tyr-131, Tyr-321, and the
      carboxyl tail appear to be important in determining receptor uptake.

PMID- 9169426
TI  - A repertoire of novel antibacterial diastereomeric peptides with selective
      cytolytic activity.
AB  - The increase in infectious diseases and bacterial resistance to antibiotics has
      resulted in intensive studies focusing on the use of linear, alpha-helical,
      cytolytic peptides from insects and mammals as potential drugs for new target
      sites in bacteria. Recent studies with diastereomers of the highly potent
      cytolytic peptides, pardaxin and melittin, indicate that alpha-helical structure
      is required for mammalian cells lysis but is not necessary for antibacterial
      activity. Thus, hydrophobicity and net positive charge of the polypeptide might
      confer selective antibacterial lytic activity. To test this hypothesis, a series
      of diastereomeric model peptides (12 amino acids long) composed of varying ratios
      of leucine and lysine were synthesized, and their structure and biological
      function were investigated. Peptide length and the position of D-amino acids were
      such that short peptides with stretches of only 1-3 consecutive L-amino acids
      that cannot form an alpha-helical structure were constructed. Circular dichroism
      spectroscopy showed that the peptides do not retain any detectable secondary
      structure in a hydrophobic environment. This enabled examination of the sole
      effect of hydrophobicity and positive charge on activity. The data reveal that
      modulating hydrophobicity and positive charge is sufficient to confer
      antibacterial activity and cell selectivity. A highly hydrophobic diastereomer
      that permeated both zwitterionic and negatively charged phospholipid vesicles,
      lysed eukaryotic and prokaryotic cells. In contrast, a highly positively charged
      diastereomer that only permeated slightly negatively charged phospholipid
      vesicles had low antibacterial activity and could not lyse eukaryotic cells. In
      the boundary between high hydrophobicity and high positive charge, the
      diastereomers acquired selective and potent antibacterial activity. Furthermore,
      they were completely resistant to human serum inactivation, which dramatically
      reduces the activity of native antibacterial peptides. In addition, a strong
      synergistic effect was observed at nonlethal concentrations of the peptides with
      the antibiotic tetracycline on resistant bacteria. The results are discussed in
      terms of proposed mechanisms of antibacterial activity, as well as a new strategy
      for the design of a repertoire of short, simple, and easily manipulated
      antibacterial peptides as potential drugs in the treatment of infectious
      diseases.

PMID- 9169427
TI  - Primary structure and catalytic mechanism of the epoxide hydrolase from
      Agrobacterium radiobacter AD1.
AB  - The epoxide hydrolase gene from Agrobacterium radiobacter AD1, a bacterium that
      is able to grow on epichlorohydrin as the sole carbon source, was cloned by means
      of the polymerase chain reaction with two degenerate primers based on the N
      terminal and C-terminal sequences of the enzyme. The epoxide hydrolase gene coded
      for a protein of 294 amino acids with a molecular mass of 34 kDa. An identical
      epoxide hydrolase gene was cloned from chromosomal DNA of the closely related
      strain A. radiobacter CFZ11. The recombinant epoxide hydrolase was expressed up
      to 40% of the total cellular protein content in Escherichia coli BL21(DE3) and
      the purified enzyme had a kcat of 21 s-1 with epichlorohydrin. Amino acid
      sequence similarity of the epoxide hydrolase with eukaryotic epoxide hydrolases,
      haloalkane dehalogenase from Xanthobacter autotrophicus GJ10, and bromoperoxidase
      A2 from Streptomyces aureofaciens indicated that it belonged to the alpha/beta
      hydrolase fold family. This conclusion was supported by secondary structure
      predictions and analysis of the secondary structure with circular dichroism
      spectroscopy. The catalytic triad residues of epoxide hydrolase are proposed to
      be Asp107, His275, and Asp246. Replacement of these residues to Ala/Glu, Arg/Gln,
      and Ala, respectively, resulted in a dramatic loss of activity for
      epichlorohydrin. The reaction mechanism of epoxide hydrolase proceeds via a
      covalently bound ester intermediate, as was shown by single turnover experiments
      with the His275 --> Arg mutant of epoxide hydrolase in which the ester
      intermediate could be trapped.

PMID- 9169428
TI  - A region of vitamin K-dependent protein S that binds to C4b binding protein
      (C4BP) identified using bacteriophage peptide display libraries.
AB  - Vitamin K-dependent protein S, a blood coagulation inhibitor, interacts with the
      C4b-binding protein (C4BP) in human plasma with high affinity (KD = 0.1 nM).
      Identification of a portion of protein S that binds to C4BP has been approached
      using random libraries of 6- and 15-mer peptides displayed on bacteriophage
      surfaces. Bacteriophage binding to the beta-chain of C4BP were selected in
      several rounds of affinity purification with intervening amplification in E.
      coli. Homology searches of the affinity purified peptide sequences against
      protein S led to the identification of four regions in protein S that were
      similar to several of the selected peptides. These regions were synthesized as
      linear peptides and tested in inhibition experiments. Only one distinct peak
      (around position 450) was observed when the homology scores versus human protein
      S sequence were averaged over all affinity purified peptides. A synthetic peptide
      comprising residues 439-460 in human protein S was found to inhibit protein S
      binding to C4BP. The same result was found with two overlapping peptides
      (residues 447-468 and 435-468, respectively) in a second set of synthetic
      peptides. Direct binding of the peptides to C4BP was inferred from titrations
      monitored by recording the near UV circular dichroism spectra or the polarization
      of tryptophan fluorescence. The results suggest that residues 447-460 constitute
      a portion of protein S that is important for the interaction with C4BP. These
      findings may have implications for patients suffering from thrombosis, due to the
      lack of free protein S, by directing the design of drugs that disrupt protein S
      binding to C4BP.

PMID- 9169429
TI  - Suppression of substance P biosynthesis in sensory neurons of dorsal root
      ganglion by prodrug esters of potent peptidylglycine alpha-amidating
      monooxygenase inhibitors.
AB  - Substance P as well as many other neuropeptides are synthesized as glycine
      extended precursors and converted to the biologically active C-terminal amides by
      posttranslational modification. The final step of posttranslational processing is
      catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM). In a previous
      study, N-substituted homocysteine analogs were found to be potent inhibitors of
      PAM partially purified from conditioned medium of cultured rat medullary thyroid
      carcinoma CA-77 cells. These compounds, however, were only modest inhibitors of
      substance P production in cultured dorsal root ganglion cells, possibly because
      of poor cell penetration. Several ester derivatives of hydrocinnamoyl
      phenylalanyl-homocysteine, one of the most potent PAM inhibitors, were prepared
      to increase the intracellular accessibility of these compounds. Hydrocinnamoyl
      phenylalanyl-(S-benzoyl-homocysteine) benzyl ester was identified as the most
      potent compound, inhibiting substance P biosynthesis in dorsal root ganglion
      cells with an IC50 of 2 microM. Inhibition of PAM resulted in a concomitant
      increase in the glycine-extended substance p (substance P-Gly) precursor peptide.
      In the presence of 3 microM benzyl ester derivative, the intracellular substance
      P-Gly level was 2.4-fold higher while the substance P level was 2.1-fold lower
      than the corresponding peptides in control cells. These results suggest that PAM
      inhibition represents an effective method for suppression of substance P
      biosynthesis and, therefore, may have therapeutic utility in conditions
      associated with elevated substance P levels. Furthermore, PAM inhibition may also
      prove useful in decreasing other amidated peptides.

PMID- 9169430
TI  - Kinetic analysis of pairing and strand exchange catalyzed by RecA. Detection by
      fluorescence energy transfer.
AB  - RecA is a 38-kDa protein from Escherichia coli that polymerizes on single
      stranded DNA, forming a nucleoprotein filament that pairs with homologous duplex
      DNA and carries out strand exchange in vitro. In this study, we measured RecA
      catalyzed pairing and strand exchange in solution by energy transfer between
      fluorescent dyes on the ends of deoxyribo-oligonucleotides. By varying the
      position of the dyes in separate assays, we were able to detect the pairing of
      single-stranded RecA filament with duplex DNA as an increase in energy transfer,
      and strand displacement as a decrease in energy transfer. With these assays, the
      kinetics of pairing and strand displacement were studied by stopped-flow
      spectrofluorometry. The data revealed a rapid, second order, reversible pairing
      step that was followed by a slower, reversible, first order strand exchange step.
      These data indicate that an initial unstable intermediate exists which can
      readily return to reactants, and that a further, rate-limiting step (or steps) is
      required to effect or complete strand exchange.

PMID- 9169431
TI  - Structure-function analysis of the mRNA cap methyltransferase of Saccharomyces
      cerevisiae.
AB  - The Saccharomyces cerevisiae mRNA cap methylating enzyme is a 436-amino acid
      protein encoded by the essential ABD1 gene. To identify structural features of
      ABD1 required for enzyme function, we introduced alanine mutations at 19
      positions within a 205-amino acid region of similarity to the methyltransferase
      domain of the vaccinia capping enzyme. Three new recessive lethal mutations,
      E170A, D194A, and R206A, were identified. Structure-function relationships were
      clarified by introducing conservative substitutions at Glu-170, Asp-194, and Arg
      206, and at Tyr-254 (an essential residue identified previously). Alleles E170D
      and D194E were viable, whereas E170Q and D194N were lethal; hence, acidic side
      chains were critical at both positions. R206K was viable, suggesting that a basic
      residue sufficed. Y254S was lethal, whereas Y254F was viable, albeit slow
      growing; thus, an aromatic side chain was important. The ABD1 mutations that were
      deleterious in vivo elicited catalytic defects in vitro. By studying the effects
      of amino- and carboxyl-terminal deletions, we defined a fully active catalytic
      domain of ABD1 from residues 130 to 426. Residues 110-129 were dispensable for
      methyltransferase activity in vitro, but essential for function in vivo. This
      analysis allowed us to delineate a subfamily of ABD1-like proteins within the
      superfamily of AdoMet-dependent methyltransferases. In addition, we identify a
      candidate Caenorhabditis elegans gene encoding a putative cap methyltransferase.
      All residues essential for ABD1 activity are conserved in the C. elegans
      homologue.

PMID- 9169432
TI  - Copurification of vimentin, energy metabolism enzymes, and a MER5 homolog with
      nucleoside diphosphate kinase. Identification of tissue-specific interactions.
AB  - Chromatography on immobilized antibodies specific to nucleoside diphosphate (NDP)
      kinase was utilized for affinity purification of this enzyme from detergent
      extracts of frog heart post-mitochondrial fractions. SDS-polyacrylamide gel
      electrophoresis analysis of eluates from these supports shows that five
      polypeptides co-purify with nucleoside diphosphate (NDP) kinase. Tryptic digests
      of each band were analyzed by mass spectrometric microsequencing. Data base
      searches by peptide mass matching and sequence homology led to the identification
      of these proteins as glyceraldehyde-3-phosphate dehydrogenase (40 kDa), creatine
      kinase (45 kDa), vimentin (55 kDa), pyruvate kinase (60 kDa), and a putative
      member of the antioxidant protein family (28 kDa). Distinct protein compositions
      were found in eluates of lung and liver extracts processed in a like manner. The
      28-kDa band and vimentin were associated with NDP kinase from all tissues, but co
      purification of pyruvate kinase was seen only in liver, while creatine kinase and
      glyceraldehyde-3-phosphate dehydrogenase were absent from eluates from lung and
      liver. The results suggest that while NDP kinase is associated with vimentin
      intermediate filaments and an antioxidant protein in most tissues, it interacts
      with energy metabolism enzymes in a tissue-specific manner.

PMID- 9169433
TI  - Analysis of the transmembrane topology and membrane assembly of the GAT-1 gamma
      aminobutyric acid transporter.
AB  - The transmembrane topology of the Na+- and Cl--dependent gamma-aminobutyric acid
      transporter GAT-1 has been studied using protein chimeras in Xenopus oocytes. A
      series of COOH-terminal truncations was generated to which a prolactin epitope
      was fused. Following expression of transporter-prolactin chimeras in Xenopus
      oocytes, the transmembrane orientation of each chimera was determined by testing
      for protease sensitivity in an oocyte membrane preparation. Data from protease
      protection assays with GAT-1-prolactin chimeras has shown that residues in the
      loops connecting hydrophobic domain (HD)3 and HD4 and HD7 and HD8 are accessible
      to protease in the cytoplasm and suggest the presence of pore loop structures
      which extend into the membrane from the extracellular face. Such pore loop
      structures may be involved in the formation of the substrate-binding pocket.
      Studies presented herein confirm that the NH2 and COOH termini are cytosolic and
      hydrophobic domains span the membrane in a manner consistent with the predicted
      hydropathy model for Na+- and Cl--dependent transporters. These data also provide
      insight into GAT-1 transmembrane assembly and suggest that a complex series of
      topogenic sequences directs this process. A potential pause-transfer sequence has
      been identified and may be responsible for the translocational pausing observed
      in this study.

PMID- 9169434
TI  - Effects of oxygen concentration on the expression of cytochrome c and cytochrome
      c oxidase genes in yeast.
AB  - Oxygen is an important environmental regulator for the transcription of several
      genes in Saccharomyces cerevisiae, but it is not yet clear how this yeast or
      other eukaryotes actually sense oxygen. To begin to address this we have examined
      the effects of oxygen concentration on the expression of several nuclear genes
      (CYC1, CYC7, COX4, COX5a, COX5b, COX6, COX7, COX8, and COX9) for proteins of the
      terminal portion of the respiratory chain. COX5b and CYC7 are hypoxic genes; the
      rest are aerobic genes. We have found that the level of expression of these genes
      is determined by oxygen concentration per se and not merely the presence or
      absence of oxygen and that each of these genes has a low oxygen threshold (0. 5-1
      microM O2) for expression. For some aerobic genes (COX4, COX5a, COX7, COX8, and
      COX9) there is a gradual decline in expression between 200 microM O2 (air) and
      their oxygen threshold. Below this threshold expression drops precipitously. For
      others (COX5a and CYC1) the level of expression is nearly constant between 200
      microM O2 and their threshold and then drops off. The hypoxic genes COX5b and
      CYC7 are not expressed until the oxygen concentration is below 0.5 microM O2.
      These studies have also revealed that COX5a and CYC1, the genes for the aerobic
      isoforms of cytochrome c oxidase subunit V and cytochrome c, and COX5b and CYC7,
      the genes for the hypoxic isoforms of cytochrome c oxidase subunit V and
      cytochrome c, are coexpressed at a variety of oxygen concentrations and switch on
      or off at extremely low oxygen concentrations. By shifting cells from one oxygen
      concentration to another we have found that aerobic genes are induced faster than
      hypoxic genes and that transcripts from both types of gene are turned over
      quickly. These findings have important implications for cytochrome c oxidase
      function and biogenesis and for models of oxygen sensing in yeast.

PMID- 9169435
TI  - Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor
      receptor activation.
AB  - The syndecan family of transmembrane heparan sulfate proteoglycans is abundant on
      the surface of all adherent mammalian cells. Syndecans bind and modify the action
      of various growth factors/cytokines, proteases/antiproteases, cell adhesion
      molecules, and extracellular matrix components. Syndecan expression is highly
      regulated during wound repair, a process orchestrated by many of these effectors.
      Each syndecan ectodomain is shed constitutively by cultured cells, but the
      mechanism and significance of this shedding are not understood. Therefore, we
      examined (i) whether physiological agents active during wound repair influence
      syndecan shedding, and (ii) whether wound fluids contain shed syndecan
      ectodomains. Using SVEC4-10 endothelial cells we find that certain proteases and
      growth factors accelerate shedding of the syndecan-1 and -4 ectodomains. Protease
      accelerated shedding is completely inhibited by serum-containing media. Thrombin
      activity is duplicated by the 14-amino acid thrombin receptor agonist peptide
      that directly activates the thrombin receptor and is not inhibited by serum.
      Epidermal growth factor family members accelerate shedding but FGF-2, platelet
      derived growth factor-AB, transforming growth factor-beta, tumor necrosis factor
      alpha, and vascular endothelial cell growth factor 165 do not. Shed ectodomains
      are soluble, stable in the conditioned medium, have the same size core proteins
      regardless whether shed at a basal rate, or accelerated by thrombin or epidermal
      growth factor-family members and are found in acute human dermal wound fluids.
      Thus, shedding is accelerated by activation of at least two distinct receptor
      classes, G protein-coupled (thrombin) and protein tyrosine kinase (epidermal
      growth factor). Proteases and growth factors active during wound repair can
      accelerate syndecan shedding from cell surfaces. Regulated shedding of syndecans
      suggests physiological roles for the soluble proteoglycan ectodomains.

PMID- 9169436
TI  - Exploring subunit-subunit interactions in the Escherichia coli bo-type ubiquinol
      oxidase by extragenic suppressor mutation analysis.
AB  - Cytochrome bo-type ubiquinol oxidase is a four-subunit heme-copper terminal
      oxidase and functions as a redox-coupled proton pump in the aerobic respiratory
      chain of Escherichia coli. On the basis of deletion and chemical cross-linking
      analyses on subunit IV, we proposed that subunit IV is essential for CuB binding
      to subunit I and that it is present in a cleft between subunits I and III (Saiki,
      K., Nakamura, H., Mogi, T., and Anraku, Y. (1996) J. Biol. Chem. 271, 15336
      15340). To extend previous studies, we carried out alanine-scanning mutagenesis
      for selected 16-amino acid residues in subunit IV to explore subunit-subunit
      interactions in bo-type ubiquinol oxidase. We found that only the replacement of
      Phe83 in helix III resulted in the reduction of the catalytic activity but that
      this did not significantly affect the UV-visible spectroscopic properties and the
      copper content. This suggests that individual amino acid substitutions, including
      the six invariant residues, are not enough to alter such properties of the metal
      centers. Extragenic suppressor mutations were isolated for the Phe83 --> Ala
      mutation of subunit IV and identified as missense mutations in helices VII and
      VIII in subunit I. These observations provide further support for specific
      interactions of subunit IV with helix VII and/or VIII, the CuB binding domain, of
      subunit I and suggest that subunit IV functions as a domain-specific molecular
      chaperon in the oxidase complex.

PMID- 9169437
TI  - Novel genes encoding 2-aminophenol 1,6-dioxygenase from Pseudomonas species AP-3
      growing on 2-aminophenol and catalytic properties of the purified enzyme.
AB  - 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas
      sp. AP-3 grown on 2-aminophenol. The product from 2-aminophenol by catalysis of
      the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas
      chromatographic and mass spectrometric analyses. The molecular mass of the native
      enzyme was 140 kDa based on gel filtration. It was dissociated into molecular
      mass subunits of 32 (alpha-subunit) and 40 kDa (beta-subunit) by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a
      heterotetramer of alpha2beta2. The genes coding for the alpha- and beta-subunits
      of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA
      and amnB) were 816 and 918 base pairs in length, respectively. The amino acid
      sequences predicted from the open reading frames of amnA and amnB corresponded to
      the NH2-terminal amino acid sequences of the alpha-subunit (AmnA) and beta
      subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed
      identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are
      homoprotocatechuate 2,3-dioxygenases from Escherichia coli W and C, respectively,
      belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had
      identity (23.3%) with only AmnB among the enzymes examined.

PMID- 9169438
TI  - Activation of the calcium-permeable cation channel CD20 by alpha subunits of the
      Gi protein.
AB  - When the calcium-permeable cation channel CD20 is expressed in Balb/c 3T3 cells,
      it is activated by insulin-like growth factor-I (IGF-I) via the IGF-I receptor
      (Kanzaki, M., Nie, L., Shibata, H., and Kojima, I. (1997) J. Biol. Chem. 272,
      4964-4969). The present study was conducted to investigate the role of G proteins
      in the regulation of the CD20 channel. In the excised patch clamp mode,
      activation of the CD20 channel by IGF-I required GTP, Mg2+, and ATP in the bath
      solution, and removal of either GTP or ATP attenuated the activation. Non
      hydrolyzable ATP could substitute for ATP, and guanyl-5'-yl thiophosphate blocked
      the activation of the channel by IGF-I. The CD20 channel was also activated by
      guanosine 5'-3-O-(thio)triphosphate, and ATP was not required for the activation.
      Addition of a preparation of Gi/Go holoprotein purified from bovine brain
      activated the CD20, and the beta-adrenergic receptor kinase peptide did not
      affect the number of channel openings induced by the G protein. The CD20 channel
      was stimulated by the GTP-bound form of recombinant Gi2 alpha subunit purified
      from Sf9 cells. The Gi3 alpha subunit was less effective, and the Gi1 alpha
      subunit had no effect. Purified recombinant beta1gamma2 subunits did not affect
      the activity of the channel. Finally, IGF-I-induced activation of CD20 was
      inhibited by an antibody against Gi2 alpha subunit. These findings indicate that
      the CD20 channel expressed in Balb/c 3T3 cells is activated by the IGF-I receptor
      via the alpha subunits of heterotrimeric G proteins.

PMID- 9169439
TI  - Thrombspondin acts via integrin-associated protein to activate the platelet
      integrin alphaIIbbeta3.
AB  - Integrin-associated protein (IAP or CD47) is a receptor for the cell/platelet
      binding domain (CBD) of thrombospondin-1 (TS1), the most abundant protein of
      platelet alpha granules. Although it associates with alphaIIbbeta3, IAP has no
      known function in platelets. TS1, the CBD, and an IAP agonist peptide (4N1K) from
      the CBD of TS1 activate the platelet integrin alphaIIbbeta3, resulting in
      platelet spreading on immobilized fibrinogen, stimulation of platelet
      aggregation, and enhanced tyrosine phosphorylation of focal adhesion kinase.
      Furthermore, 4N1K peptide selectively stimulates the phosphorylation of LYN and
      SYK and their association with FAK. The phosphorylation of SYK is blocked by
      pertussis toxin, implicating a Gi-like heterotrimeric G protein. IAP solublized
      from membranes of unstimulated platelets binds specifically to an affinity column
      of 4N1K peptide. Both alphaIIb and beta3 integrin subunits and c-Src bind along
      with IAP. This complex of proteins is also detected with immunoprecipitation.
      Activation of platelets with the agonist peptide 4N1K results in the association
      of FAK with the IAP-alphaIIbbeta3 complex. Thus an important function of TS1 in
      platelets is that of a secreted costimulator of alphaIIbbeta3 whose unique
      properties result in its localization to the platelet surface and the fibrin
      clot.

PMID- 9169440
TI  - Transcription elongation through DNA arrest sites. A multistep process involving
      both RNA polymerase II subunit RPB9 and TFIIS.
AB  - The role of yeast RNA polymerase II (pol II) subunit RPB9 in transcript
      elongation was investigated by examining the biochemical properties of pol II
      lacking RPB9 (pol IIDelta9). The maximal rate of chain elongation was nearly
      identical for pol II and pol IIDelta9. By contrast, pol IIDelta9 elongated more
      efficiently through DNA sequences that signal the elongation complex to pause or
      arrest. The addition of purified recombinant RPB9 to pol IIDelta9 restored the
      elongation properties of the mutant polymerase to those of the wild-type enzyme.
      Arrested pol IIDelta9 complexes were refractory to levels of TFIIS that promoted
      maximal read-through with pol II. However, both pol II and pol IIDelta9 complexes
      stimulated with TFIIS undergo transcript cleavage, confirming that transcript
      cleavage and read-through activities can be uncoupled. Our observations suggest
      that both TFIIS and RPB9 are required to stimulate the release of RNA polymerase
      II from the arrested state.

PMID- 9169441
TI  - RNA polymerase III transcription repressed by Rb through its interactions with
      TFIIIB and TFIIIC2.
AB  - The retinoblastoma susceptibility gene product (Rb) generally represses RNA
      polymerase III (Pol III)-directed transcription. This implies that Rb interacts
      with essential transcription factors. Mutations in either the A or B subdomains
      in the Rb pocket interfere with Rb-mediated repression of Pol III-directed
      transcription, which indicates that both subdomains are directly involved in this
      activity. Addition of either purified TFIIIB or purified TFIIIC2 partially
      relieves Rb-mediated repression and restores activity to nuclear extracts that
      had been depleted of essential factors by binding to Rb. Pull down and
      coimmunoprecipitation experiments as well as functional assays indicate that Rb
      interacts with both TFIIIB and TFIIIC2 and that the A subdomain is primarily
      required for binding TFIIIB and the B subdomain for binding TFIIIC2. While Rb
      interacts with both factors, the A subdomain is more important than the B
      subdomain in directing Rb-mediated repression, and TFIIIB is the principal target
      of that activity.

PMID- 9169442
TI  - Rhodopsin phosphorylation sites and their role in arrestin binding.
AB  - Rhodopsin, the rod cell photoreceptor, undergoes rapid desensitization upon
      exposure to light, resulting in uncoupling of the receptor from its G protein,
      transducin (Gt). Phosphorylation of serine and threonine residues located in the
      COOH terminus of rhodopsin is the first step in this process, followed by the
      binding of arrestin. In this study, a series of mutants was generated in which
      these COOH-terminal phosphorylation substrate sites were substituted with
      alanines. These mutants were expressed in HEK-293 cells and analyzed for their
      ability to be phosphorylated by rhodopsin kinase and to bind arrestin. The
      results demonstrate that rhodopsin kinase can efficiently phosphorylate other
      serine and threonine residues in the absence of the sites reported to be the
      preferred substrates for rhodopsin kinase. A correlation was observed between the
      level of rhodopsin phosphorylation and the amount of arrestin binding to these
      mutants. However, mutants T340A and S343A demonstrated a significant reduction in
      arrestin binding even though the level of phosphorylation was similar to that of
      wild-type rhodopsin. Substitution of Thr-340 and Ser-343 with glutamic acid
      residues (T340E and S343E, respectively) was not sufficient to promote the
      binding of arrestin in the absence of phosphorylation by rhodopsin kinase. When
      S343E was phosphorylated, its ability to bind arrestin was similar to that of
      wild-type rhodopsin. Surprisingly, arrestin binding to phosphorylated T340E did
      not increase to the level observed for wild-type rhodopsin. These results suggest
      that 2 amino acids, Thr-340 and Ser-343, play important but distinct roles in
      promoting the binding of arrestin to rhodopsin.

PMID- 9169443
TI  - Purification and cloning of a broad substrate specificity human liver
      carboxylesterase that catalyzes the hydrolysis of cocaine and heroin.
AB  - A human liver carboxylesterase (hCE-2) that catalyzes the hydrolysis of the
      benzoyl group of cocaine and the acetyl groups of 4-methylumbelliferyl acetate,
      heroin, and 6-monoacetylmorphine was purified from human liver. The purified
      enzyme exhibited a single band on SDS-polyacrylamide gel electrophoresis with a
      subunit mass of approximately 60 kDa. The native enzyme was monomeric. The
      isoelectric point of hCE-2 was approximately 4.9. Treatment with endoglycosidase
      H caused an increase in electrophoretic mobility indicating that the liver
      carboxylesterase was a glycoprotein of the high mannose type. The complete cDNA
      nucleotide sequence was determined. The authenticity of the cDNA was confirmed by
      a perfect sequence match of 78 amino acids derived from the hCE-2 purified from
      human liver. The mature 533-amino acid enzyme encoded by this cDNA shared highest
      sequence identity with the rabbit liver carboxylesterase form 2 (73%) and the
      hamster liver carboxylesterase AT51p (67%). Carboxylesterases with high sequence
      identity to hCE-2 have not been reported in mouse and rat liver. hCE-2 exhibited
      different drug ester substrate specificity from the human liver carboxylesterase
      called hCE-1, which hydrolyzes the methyl ester of cocaine. hCE-2 had higher
      catalytic efficiencies for hydrolysis of 4-methylumbelliferyl acetate, heroin,
      and 6-monoacetylmorphine and greater inhibition by eserine than hCE-1. hCE-2 may
      play an important role in the degradation of cocaine and heroin in human tissues.

PMID- 9169444
TI  - Mutations of pma-1, the gene encoding the plasma membrane H+-ATPase of Neurospora
      crassa, suppress inhibition of growth by concanamycin A, a specific inhibitor of
      vacuolar ATPases.
AB  - Concanamycin A (CCA), a specific inhibitor of vacuolar ATPases, inhibited growth
      of Neurospora crassa in medium adjusted to pH 7 or above. Mutant strains were
      selected for growth on medium containing 1.0 microM CCA. Sixty-four (of 66)
      mutations mapped in the region of the pma1 locus, which encodes the plasma
      membrane H+-ATPase. Analysis of V-ATPase activity in isolated vacuolar membranes
      from the mutant strains showed wild-type activity and sensitivity to CCA. In
      contrast, plasma membrane H+-ATPase activity in isolated plasma membranes from
      the mutants was reduced as compared with wild-type, and in four strains the
      activity showed increased resistance to vanadate. The most interesting change in
      the plasma membrane H+-ATPase was in kinetic behavior. The wild-type enzyme
      showed sigmoid dependence on MgATP concentration with a Hill number of 2.0, while
      the seven mutants tested exhibited hyperbolic kinetics with a Hill number of 1.0.
      One interpretation of these data was that the enzyme had changed from a
      functional dimer to a functional monomer. Mutation of the plasma membrane H+
      ATPase did not confer resistance by preventing uptake of CCA. In the presence of
      CCA both wild-type and mutant strains were unable to accumulate arginine, failed
      to concentrate chloroquine in acidic vesicles, and exhibited gross alterations in
      hyphal morphology, indicating that the CCA had entered the cells and inactivated
      the V-ATPase. Instead, we hypothesize that the mutations conferred resistance
      because the altered plasma membrane H+-ATPase could more efficiently rid the cell
      of toxic levels of Ca2+ or protons or other ions accumulated in the cytoplasm
      following inactivation of the V-ATPase by CCA.

PMID- 9169445
TI  - Lck-independent triggering of T-cell antigen receptor signal transduction by
      staphylococcal enterotoxins.
AB  - Superantigens (SAgs) activate T-cells in a manner specific to the Vbeta region of
      the T-cell antigen receptor. Stimulations by SAgs provoke drastic T-cell
      activation that leads to programmed cell death or the anergic state of responding
      cells. To characterize the signal transduction pathway initiated by SAgs, mutant
      lines derived from the human leukemic T-cell line Jurkat were tested for their
      reactivities against prototypic SAgs, staphylococcal enterotoxins. The J.CaM1.6
      cell line, which lacks Lck expression and lost reactivity against T-cell antigen
      receptor-mediated stimulation, was activated by staphylococcal enterotoxins in a
      manner indistinguishable from the Jurkat cell line. In contrast, the J.45. 01
      cell line, which lacks expression of functional CD45, showed severely impaired
      reactivity. The role of Lck appears to be replaced by another Src family protein
      tyrosine kinase, Fyn. In J.CaM1.6 cells, Fyn was rapidly phosphorylated and
      activated after staphylococcal enterotoxin treatment. The kinase-inactive mutant
      of Fyn significantly suppressed the reactivity against staphylococcal enterotoxin
      E in J.CaM1.6 cells, and the expression of the active form of Fyn reconstituted
      reactivity against staphylococcal enterotoxin E in J.45.01 cells. These results
      demonstrate that SAgs activate T-cells in an Lck-independent pathway and that Fyn
      plays a critical role in the process.

PMID- 9169446
TI  - Snmp-1, a novel membrane protein of olfactory neurons of the silk moth Antheraea
      polyphemus with homology to the CD36 family of membrane proteins.
AB  - While olfactory neurons of silk moths are well known for their exquisite
      sensitivity to sex pheromone odorants, molecular mechanisms underlying this
      sensitivity are poorly understood. In searching for proteins that might support
      olfactory mechanisms, we characterized the protein profile of olfactory neuron
      receptor membranes of the wild silk moth Antheraea polyphemus. We have purified
      and cloned a prominent 67-kDa protein which we have named Snmp-1 (sensory neuron
      membrane protein-1). Northern blot analysis suggests that Snmp-1 is uniquely
      expressed in antennal tissue; in situ hybridization and immunocytochemical
      analyses show that Snmp-1 is expressed in olfactory neurons and that the protein
      is localized to the cilia, dendrites, and somata but not the axons. Snmp-1 mRNA
      expression increases significantly 1-2 days before the end of adult development,
      coincident with the functional maturation of the olfactory system. Sequence
      analysis suggests Snmp-1 is homologous with the CD36 protein family, a
      phylogenetically diverse family of receptor-like membrane proteins. CD36 family
      proteins are characterized as having two transmembrane domains and interacting
      with proteinaceous ligands; Snmp-1 is the first member of this family identified
      in nervous tissue. These findings argue that Snmp-1 has an important role in
      olfaction; possible roles of Snmp-1 in odorant detection are discussed.

PMID- 9169447
TI  - Phosphorylation of serine 256 is required for cAMP-dependent regulatory
      exocytosis of the aquaporin-2 water channel.
AB  - The aquaporin-2 (AQP2) vasopressin water channel is translocated to the apical
      membrane upon vasopressin stimulation. Phosphorylation of serine 256 of AQP2 by
      cAMP-dependent protein kinase has been shown, but its relation to vasopressin
      regulated translocation has not been elucidated. To address this question, wild
      type (WT) AQP2 and a mutant with alanine in place of serine 256 of AQP2 (S256A)
      were expressed in LLC-PK1 cells by electroporation. Measurements by a stopped
      flow light-scattering method revealed that the osmotic water permeability (Pf) of
      LLC-PK1 cells transfected with WT was 69.6 +/- 6.5 microm/s (24.8 +/- 2.2
      microm/s for mock-transfected), and stimulation by 500 microM 8-(4
      chlorophenylthio)-cAMP increased the Pf by 85 +/- 12%. When S256A AQP2 was
      transfected, the cAMP-dependent increase in the Pf was only 8 +/- 5%. After cAMP
      stimulation, the increase in surface expression of AQP2 determined by surface
      biotin labeling was 4 +/- 10%, significantly less than that for WT (88 +/- 5%).
      In addition, an in vivo [32P]orthophosphate labeling assay demonstrated
      significant phosphorylation of WT AQP2 and only minimal phosphorylation of S256A
      AQP2 in LLC-PK1 cells. Our results indicated that serine 256 of AQP2 is necessary
      for regulatory exocytosis and that cAMP-responsive redistribution of AQP2 may be
      regulated by phosphorylation of AQP2.

PMID- 9169448
TI  - A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and
      human dorsal root ganglia.
AB  - Dorsal root ganglion neurons express a wide repertoire of sodium channels with
      different properties. Here, we report the cloning from rat, dorsal root ganglia
      (DRG), cellular expression, and functional analysis of a novel tetrodotoxin
      sensitive peripheral sodium channel (PN), PN1. PN1 mRNA is expressed in many
      different tissues. Within the rat DRG, both the mRNA and PN1-like
      immunoreactivity are present in small and large neurons. The abundance of sodium
      channel mRNAs in rat DRG is rBI > PN1 >/= PN3 >>> rBIII by quantitative reverse
      transcription-polymerase chain reaction analysis. Data from reverse transcription
      polymerase chain reaction and sequence analyses of human DRG and other human
      tissues suggest that rat PN1 is an ortholog of the human neuroendocrine channel.
      In Xenopus oocytes, PN1 exhibits kinetics that are similar to rBIIa sodium
      currents and is inhibited by tetrodotoxin with an IC50 of 4.3 +/- 0.92 nM. Unlike
      rBIIa, the inactivation kinetics of PN1 are not accelerated by the coexpression
      of the beta-subunits.

PMID- 9169449
TI  - Identification of structural elements of a scorpion alpha-neurotoxin important
      for receptor site recognition.
AB  - alpha-Neurotoxins from scorpion venoms constitute the most studied group of
      modifiers of the voltage-sensitive sodium channels, and yet, their toxic site has
      not been characterized. We used an efficient bacterial expression system for
      modifying specific amino acid residues of the highly insecticidal alpha
      neurotoxin LqhalphaIT from the scorpion Leiurus quinquestriatus hebraeus. Toxin
      variants modified at tight turns, the C-terminal region, and other structurally
      related regions were subjected to neuropharmacological and structural analyses.
      This approach highlighted both aromatic (Tyr10 and Phe17) and positively charged
      (Lys8, Arg18, Lys62, and Arg64) residues that (i) may interact directly with
      putative recognition points at the receptor site on the sodium channel; (ii) are
      important for the spatial arrangement of the toxin polypeptide; and (iii)
      contribute to the formation of an electrostatic potential that may be involved in
      biorecognition of the receptor site. The latter was supported by a suppressor
      mutation (E15A) that restored a detrimental effect caused by a K8D substitution.
      The feasibility of producing anti-insect scorpion neurotoxins with augmented
      toxicity was demonstrated by the substitution of the C-terminal arginine with
      histidine. Altogether, the present study provides for the first time an insight
      into the putative toxic surface of a scorpion neurotoxin affecting sodium channel
      gating.

PMID- 9169450
TI  - Visualization of G protein-coupled receptor trafficking with the aid of the green
      fluorescent protein. Endocytosis and recycling of cholecystokinin receptor type
      A.
AB  - A chimeric protein consisting of the cholecystokinin receptor type A (CCKAR) and
      the green fluorescent protein (GFP) was used for studying receptor localization,
      internalization, and recycling in live cells in real time in four different cell
      lines. Fusion of the C terminus of the CCKAR to the N terminus of the GFP did not
      alter receptor ligand binding affinity, signal transduction, or the pattern of
      receptor surface expression and receptor-mediated cholecystokinin (CCK)
      internalization. The use of a new GFP mutant with increased fluorescence allowed
      the continuous observation of CCKAR-GFP in stably expressing cell lines. Newly
      obtained biologically active fluorescent derivatives of CCK were used for
      simultaneous observation of receptor and ligand trafficking in CHO, NIH/3T3, and
      HeLa cells stably expressing the fluorescent CCKAR and in transiently transfected
      COS-1 cells. Receptor internalization was predominantly ligand dependent in HeLa,
      COS-1, and CHO cells, but was mostly constitutive in NIH/3T3 cells, suggesting
      the existence of cell-specific regulation of receptor internalization. The CCKAR
      antagonists, L-364,718 and CCK 27-32 amide potently inhibited spontaneous
      internalization of the receptor. The average sorting time of CCK and the receptor
      in the endosomes was about 25 min. The receptor recycled back to the cell
      membrane with an average time of 60 min. While the ligands sorted to lysosomes,
      no receptor molecules could be detected there, and no receptor degradation was
      observed during recycling. These results demonstrate the usefulness of GFP
      tagging for real time imaging of G protein-coupled receptor trafficking in living
      cells and suggest that this technique may be successfully applied to the study of
      the regulation and trafficking mechanisms of other receptors.

PMID- 9169451
TI  - Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor
      coupled to the Jak/STAT pathway.
AB  - The neurotransmitter serotonin mediates a wide variety of peripheral and central
      physiological effects through the binding to multiple receptor subtypes
      (Wilkinson, L. O., and Dourish, C. T. (1991) in Serotonin Receptor Subtypes:
      Basic and Clinical Aspects (Peroutka, S. J., ed) Vol. 15, pp.147-210, Wiley-Liss,
      New York). Among them, serotonin 5-HT2A receptors are known to activate the
      phospholipase C-beta second messenger pathway (Peroutka, S. J. (1995) Trends
      Neurosci. 18, 68-69). We identified and localized in rat skeletal muscle
      myoblasts a functional serotonin 5-HT2A receptor. This receptor was detected on
      the plasma membrane, in myoblasts, and at the level of T-tubules in contracting
      myotubes. Binding of serotonin to its receptor increases the expression of genes
      involved in myogenic differentiation. Unexpectedly, the 5-HT2A receptor is able
      to activate another signaling pathway; it triggers a rapid and transient tyrosine
      phosphorylation of Jak2 kinase in response to serotonin. Jak2 auto
      phosphorylation is followed by the tyrosine phosphorylation of STAT3 (signal
      transducers and activators of transcription) and its translocation into the
      nucleus. We also find that the 5-HT2A receptor and STAT3 co-precipitate with
      Jak2, indicating that they are physically associated. We conclude that the
      serotonin 5-HT2A receptor identified in skeletal muscle myoblasts is able to
      activate the intracellular phosphorylation pathway used by cytokines. The
      presence of serotonin receptors in T-tubules suggests a role for serotonin in
      excitation-contraction coupling and (or) an effect in skeletal muscle fiber
      repairing.

PMID- 9169452
TI  - Architectural accommodation in the complex of four p53 DNA binding domain
      peptides with the p21/waf1/cip1 DNA response element.
AB  - High resolution chemical footprinting and cross-linking experiments have provided
      a basis for elucidating the overall architecture of the complex between the core
      DNA binding domain of p53 (p53DBD, amino acids 98-309) and the p21/waf1/cip1 DNA
      response element implicated in the G1/S phase cell cycle checkpoint. These
      studies complement both a crystal structure and earlier biophysical studies and
      provide the first direct experimental evidence that four subunits of p53DBD bind
      to the response element in a regular staggered array having pseudodyad symmetry.
      The invariant guanosines in the highly conserved C(A/T)|(T/A)G parts of the
      consensus half-sites are critical to the p53DBD-DNA binding. Molecular modeling
      of the complex using the observed peptide-DNA contacts shows that when four
      subunits of p53DBD bind the response element, the DNA has to bend approximately
      50 degrees to relieve steric clashes among different subunits, consistent with
      recent DNA cyclization studies. The overall lateral arrangement of the four p53
      subunits with respect to the DNA loop comprises a novel nucleoprotein assembly
      that has not been reported previously in other complexes. We suggest that this
      kind of nucleoprotein superstructure may be important for p53 binding to response
      elements packed in chromatin and for subsequent transactivation of p53-mediated
      genes.

PMID- 9169453
TI  - DNA bending is essential for the site-specific recognition of DNA response
      elements by the DNA binding domain of the tumor suppressor protein p53.
AB  - We have used circular permutation assays to determine the extent and location of
      the DNA bend induced by the DNA binding domain of human wild type p53 (p53DBD)
      upon binding to several naturally occurring DNA response elements. We have found
      that p53DBD binding induces axial bending in all of the response elements
      investigated. In particular, response elements having a d(CATG) sequence at the
      junction of two consensus pentamers in each half-site favor highly bent complexes
      (bending angle is approximately 50 degrees ), whereas response elements having
      d(CTTG) bases at this position are less bent (bending angles from approximately
      37 to approximately 25 degrees ). Quantitative electrophoretic mobility shift
      assays of different complexes show a direct correlation between the DNA bending
      angle and the binding affinity of the p53DBD with the response elements, i.e. the
      greater the stability of the complex, the more the DNA is bent by p53DBD binding.
      The study provides evidence that the energetics of DNA bending, as determined by
      the presence or absence of flexible sites in the response elements, may
      contribute significantly to the overall binding affinity of the p53DBD for
      different sequences. The results therefore suggest that both the structure and
      the stability of the p53-DNA complex may vary with different response elements.
      This variability may be correlated with variability in p53 function.

PMID- 9169454
TI  - The type II transforming growth factor-beta receptor autophosphorylates not only
      on serine and threonine but also on tyrosine residues.
AB  - The type I and type II receptors for transforming growth factor-beta (TGF-beta)
      are structurally related transmembrane serine/threonine kinases, which are able
      to physically interact with each other at the cell surface. To help define the
      initial events in TGF-beta signaling, we characterized the kinase activity of the
      type II TGF-beta receptor. A recombinant cytoplasmic domain of the receptor was
      purified from Escherichia coli and baculovirus-infected insect cells. Anti
      phosphotyrosine Western blotting demonstrated that the type II receptor kinase
      can autophosphorylate on tyrosine. Following an in vitro kinase reaction, the
      autophosphorylation of the cytoplasmic domain and phosphorylation of exogenous
      substrate was shown by phosphoamino acid analysis to occur not only on serine and
      threonine but also on tyrosine. The dual kinase specificity of the receptor was
      also demonstrated using immunoprecipitated receptors expressed in mammalian cells
      and in vivo 32P labeling showed phosphorylation of the receptor on serine and
      tyrosine. In addition, the kinase activity of the cytoplasmic domain was
      inhibited by the tyrosine kinase inhibitor tyrphostin. Tryptic mapping and amino
      acid sequencing of in vitro autophosphorylated type II receptor cytoplasmic
      domain allowed the localization of the sites of tyrosine phosphorylation to
      positions 259, 336, and 424. Replacement of all three tyrosines with
      phenylalanines strongly inhibited the kinase activity of the receptor, suggesting
      that tyrosine autophosphorylation may play an autoregulatory role for the kinase
      activity of this receptor. These results demonstrate that the type II TGF-beta
      receptor can function as a dual specificity kinase and suggest a role for
      tyrosine autophosphorylation in TGF-beta receptor signaling.

PMID- 9169455
TI  - Atrial natriuretic peptide induces apoptosis in neonatal rat cardiac myocytes.
AB  - Early heart failure is characterized by elevated plasma atrial natriuretic
      peptide (ANP) levels, but little is known about the direct effects of ANP on
      cardiac myocytes. In neonatal rat cardiac myocytes, ANP induced apoptosis in a
      dose-dependent and cell type-specific manner. Maximum effects occurred at 1
      microM ANP, with a 4-5-fold increase in apoptotic cells, reaching a maximum
      apoptotic index of 19%. In contrast, the maximum apoptotic index of ANP-treated
      non-myocytes was 1.1 +/- 0.2%, equivalent to control cultures. ANP treatment also
      sharply reduced levels of Mcl-1 mRNA, a Bcl-2 homologue, coincident with the
      increase in the incidence of apoptosis. ANP induction of apoptosis was receptor
      dependent and mediated by cyclic GMP: the effect was mimicked by 8-bromo-cGMP, a
      membrane-permeable analog, and by sodium nitroprusside, an activator of soluble
      guanylyl cyclase, and was potentiated by a cGMP-specific phosphodiesterase
      inhibitor, zaprinast. Interestingly, norepinephrine, a myocyte growth factor,
      inhibited ANP-induced apoptosis via activation of the beta-adrenergic receptor
      and elevation of cyclic AMP. These results show that ANP is a specific effector
      of cardiac myocyte apoptosis in culture via receptor-mediated elevation of cGMP.
      Furthermore, at least in this model, ANP and norepinephrine may have opposing
      roles in the modulation of cardiac myocyte growth and survival.

PMID- 9169456
TI  - A novel lipopolysaccharide-response element contributes to induction of nitric
      oxide synthase.
AB  - The gene encoding the high output isoform of nitric oxide synthase represents a
      large class of alarm and defense genes transcriptionally induced in response to
      bacterial lipopolysaccharide (LPS). The promoters of most of these genes contain
      at least two LPS-response elements, one of which commonly binds transcription
      factors of the NF-kappaB/Rel family. Here a novel LPS-response element is
      identified in the inducible nitric oxide synthase promoter, termed LREAA, which
      contains critical adenosine residues lying 19-20 base pairs downstream of the
      proximal NF-kappaB binding element (NFkappaBd). Both NFkappaBd and LREAA are
      required for LPS-induced promoter activity. A protein partially recognized by
      antibody against transcription factor Oct-1 binds to the LREAA element
      constitutively in untreated macrophages while contributing to a DNA-protein
      complex that includes NF-kappaB p50 in macrophages treated with LPS. NF-kappaB
      p50 and the LREAA-binding proteins may together recruit an LPS-triggered
      transactivator of transcription.

PMID- 9169457
TI  - Sequence specificity and biochemical characterization of the RusA Holliday
      junction resolvase of Escherichia coli.
AB  - The RusA protein of Escherichia coli is an endonuclease that resolves Holliday
      intermediates in recombination and DNA repair. Analysis of its subunit structure
      revealed that the native protein is a dimer. Its resolution activity was
      investigated using synthetic X-junctions with homologous cores. Resolution occurs
      by dual strand incision predominantly 5' of CC dinucleotides located
      symmetrically. A junction lacking homology is not resolved. The efficiency of
      resolution is related inversely to the number of base pairs in the homologous
      core, which suggests that branch migration is rate-limiting. Inhibition of
      resolution at high ratios of protein to DNA suggests that binding of RusA may
      immobilize the junction point at non-cleavable sites. Resolution is stimulated by
      alkaline pH and by Mn2+. The protein is unstable in the absence of substrate DNA
      and loses approximately 80% of its activity within 1 min under standard reaction
      conditions. DNA binding stabilizes the activity. Junction resolution is inhibited
      in the presence of RuvA. This observation probably explains why RusA is unable to
      promote efficient recombination and DNA repair in ruvA+ strains unless it is
      expressed at a high level.

PMID- 9169458
TI  - HIV-1 Tat induces the expression of the interleukin-6 (IL6) gene by binding to
      the IL6 leader RNA and by interacting with CAAT enhancer-binding protein beta (NF
      IL6) transcription factors.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is associated with severe
      psoriasis, B cell lymphoma, and Kaposi's sarcoma. A deregulated production of
      interleukin-6 (IL6) has been implicated in the pathogenesis of these diseases.
      The molecular mechanisms underlying the abnormal IL6 secretion of HIV-1-infected
      cells may include transactivation of the IL6 gene by HIV-1. Here we report the
      molecular mechanisms of Tat activity on the expression of the IL6 gene. By using
      5' deletion mutants of pIL6Pr-CAT and using IL6:HIV-1-LTR hybrid constructs where
      discrete regions of the IL6 promoter replaced the TAR sequence in HIV-1 LTR, we
      identified a short sequence of the 5'-untranslated region of the IL6 mRNA that is
      required for Tat to trans-activate the IL6 promoter. This sequence acquires a
      stem-loop structure and includes a UCU sequence that binds to Tat and is
      necessary for full trans-activation. In addition, we provide the evidence that
      Tat can function by enhancing the CAAT enhancer-binding protein (C/EBP) DNA
      binding activity and is able to complex with in vitro translated C/EBPbeta, which
      is a major mediator of IL6 promoter function. By using the yeast two-hybrid
      system and immunoprecipitation, we observed that the interaction of Tat with
      C/EBP proteins also occurred in vivo. The data are consistent with the
      possibility that Tat may function on heterologous genes by interacting with RNA
      structures possibly present in a large number of cellular and viral genes. In
      addition, Tat may function by protein-protein interactions, leading to the
      generation of heterodimers with specific transcription factors.

PMID- 9169459
TI  - Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC
      chemokine LARC.
AB  - Liver and activation-regulated chemokine (LARC) is a recently identified CC
      chemokine that is expressed mainly in the liver. LARC functions as a selective
      chemoattractant for lymphocytes that express a class of receptors specifically
      binding to LARC with high affinity. To identifiy the receptor for LARC, we
      examined LARC-induced calcium mobilization in cells stably expressing five CC
      chemokine receptors (CCR1-CCR5) and five orphan seven-transmembrane receptors.
      LARC specifically induced calcium flux in K562 cells as well as 293/EBNA-1 cells
      stably expressing an orphan receptor GPR-CY4. LARC induced migration in 293/EBNA
      1 cells stably expressing GPR-CY4 with a bi-modal dose-response curve. LARC fused
      with secreted alkaline phosphatase (LARC-SEAP) bound specifically to Raji cells
      stably expressing GPR-CY4 with a Kd of 0.9 nM. Only LARC but not five other CC
      chemokines (MCP-1, RANTES, MIP-1alpha, MIP-1beta, and TARC) competed with LARC
      SEAP for binding to GPR-CY4. By Northern blot analysis, GPR-CY4 mRNA was
      expressed mainly in spleen, lymph nodes, Appendix, and fetal liver among various
      human tissues. Among various leukocyte subsets, GPR-CY4 mRNA was detected in
      lymphocytes (CD4(+) and CD8(+) T cells and B cells) but not in natural killer
      cells, monocytes, or granulocytes. Expression of GPR-CY4 mRNA in CD4(+) and
      CD8(+) T cells was strongly up-regulated by IL-2. Taken together, GPR-CY4 is the
      specific receptor for LARC expressed selectively on lymphocytes, and LARC is a
      unique functional ligand for GPR-CY4. We propose GPR-CY4 to be designated as
      CCR6.

PMID- 9169460
TI  - Synergy between interferon-gamma and tumor necrosis factor-alpha in
      transcriptional activation is mediated by cooperation between signal transducer
      and activator of transcription 1 and nuclear factor kappaB.
AB  - Interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) cooperate
      to induce the expression of many gene products during inflammation. The present
      report demonstrates that a portion of this cooperativity is mediated by synergism
      between two distinct transcription factors: signal transducer and activator of
      transcription 1 (STAT1) and nuclear factor kappaB (NF-kappaB). IFNgamma and
      TNFalpha synergistically induce expression of mRNAs encoding interferon
      regulatory factor-1 (IRF-1), intercellular adhesion molecule-1, Mig (monokine
      induced by gamma-interferon), and RANTES (regulated on activation normal T cell
      expressed and secreted) in normal but not STAT1-deficient mouse fibroblasts,
      indicating a requirement for STAT1. Transient transfection assays in fibroblasts
      using site-directed mutants of a 1.3-kilobase pair sequence of the IRF-1 gene
      promoter revealed that the synergy was dependent upon two sequence elements; a
      STAT binding element and a kappaB motif. Artificial constructs containing a
      single copy of both a STAT binding element and a kappaB motif linked to the
      herpes virus thymidine kinase promoter were able to mediate synergistic response
      to IFNgamma and TNFalpha; such response varied with both the relative spacing and
      the specific sequence of the regions between these two sites. Cooperatively
      responsive sequence constructs bound both STAT1alpha and NF-kappaB in nuclear
      extracts prepared from IFNgamma- and/or TNFalpha-stimulated fibroblasts, although
      binding of individual factors was not cooperative. Thus, the frequently observed
      synergy between IFNgamma and TNFalpha in promoting inflammatory response depends
      in part upon cooperation between STAT1alpha and NF-kappaB, which is most likely
      mediated by their independent interaction with one or more components of the
      basal transcription complex.

PMID- 9169461
TI  - The first 5 amino acids of the carboxyl terminus of phosphatidylinositol transfer
      protein (PITP) alpha play a critical role in inositol lipid signaling. Transfer
      activity of PITP is essential but not sufficient for restoration of phospholipase
      C signaling.
AB  - Phosphatidylinositol transfer protein (PITP) is essential for phospholipase C
      signaling and for constitutive and regulated vesicular traffic. PITP has a single
      lipid-binding site that can reversibly bind phosphatidylinositol (PI) and
      phosphatidylcholine (PC) and transfer these lipids between membrane compartments
      in vitro. The role of the carboxyl terminus was examined by comparing wild-type
      PITPalpha with PITPalpha in which 5, 10, and 20 amino acids were deleted from the
      C terminus. Delta5- and Delta10-PITP had reduced PI and PC transfer activities
      compared with wild-type PITP, with the effect on PI transfer being more marked
      than that on PC transfer. Delta20-PITP was inactive at all concentrations tested.
      All three truncated mutants were unable to restore G-protein-mediated
      phospholipase Cbeta stimulation in HL-60 cells. Delta5- and Delta10-PITP, but not
      Delta20-PITP, inhibited the signaling function of wild-type protein without any
      effect on lipid transfer in vitro. We conclude that (a) the carboxyl terminus of
      PITP plays a critical role in phospholipase C signaling; (b) the transfer
      activity is not the only determining factor that dictates the restorative
      function of PITP in inositol lipid signaling; and (c) the dominant inhibitory
      effects of Delta5- and Delta10-PITP on wild-type PITP in phospholipase C
      signaling suggest the existence of a receptor for PITP.

PMID- 9169462
TI  - Activation of NF-kappaB by antineoplastic agents. Role of protein kinase C.
AB  - Paclitaxel can induce tumor necrosis factor (TNF) and interleukin-1 gene
      expression, similar to lipopolysaccharides. Since lipopolysaccharide-induced
      expression of TNF is related to activation of NF-kappaB, we determined whether NF
      kappaB could be activated by paclitaxel. In the human lung adenocarcinoma cell
      line A549, paclitaxel activated NF-kappaB in a dose-dependent manner with maximal
      activation after 2-4 h. Since paclitaxel could up-regulate TNF and interleukin-1
      secretion and subsequent NF-kappaB activation could be caused by these cytokines,
      the effect of two other groups of anticancer drugs including vinca alkaloids
      (vinblastine and vincristine) and anthracyclines (daunomycin and doxorubicin),
      neither of which induce TNF or interleukin-1 gene expression, were examined. Like
      paclitaxel, vinblastine, vincristine, daunomycin, and doxorubicin each caused
      activation of NF-kappaB. Therefore, it is unlikely that activation of NF-kappaB
      caused by these agents or by paclitaxel is mediated via cytokine up-regulation.
      Furthermore, actinomycin D and cycloheximide, inhibitors of transcription and
      translation, respectively, did not inhibit paclitaxel-induced NF-kappaB
      activation. Several other transcription factors such as AP-1, AP-2, CREB, SP-1,
      or TFIID were not activated by antineoplastic agents demonstrating specificity of
      NF-kappaB activation. The involvement of both subunits in the NF-kappaB DNA
      binding complex was demonstrated by its abrogation by anti-p65 and by supershift
      by anti-p50 antibodies. Since protein phosphorylation is implicated in the
      activation of NF-kappaB, the effect of anticancer drugs on protein kinase C
      activity was measured. Vincristine, daunomycin, and paclitaxel significantly
      increased protein kinase C activity, and vinblastine and doxorubicin caused
      similar trends. Following treatment with antineoplastics (1-4 h), cytoplasmic
      IkappaBalpha degradation occurred concomitantly with translocation of p65 to the
      nucleus. Specific protein kinase C inhibitors (bisindolylmaleimide (GF109203X)
      and calphostin C) blocked the activation of NF-kappaB by each compound. Hence,
      protein kinase C activation may contribute to NF-kappaB activation by
      antineoplastic agents.

PMID- 9169464
TI  - ST-2, a telomere and subtelomere duplex and G-strand binding protein activity in
      Trypanosoma brucei.
AB  - From Trypanosoma brucei, we identified ST-2, a protein complex that interacts
      with telomeric DNA and exhibits novel features. It binds specifically to the
      double-stranded telomere repeats (TTAGGG) and more tightly to the subtelomere 29
      base pair elements that separate the telomere repeats from their proximal
      telomere-associated sequences. Interestingly, ST-2 showed still greater affinity
      for the G-rich strand of the telomere present either as an overhang or in a
      single-stranded form, but it exhibited the highest affinity for the G-rich strand
      of the subtelomere repeats. The binding characteristics of ST-2 are complementary
      to those of ST-1, a 39-kDa polypeptide we previously identified in T. brucei
      (Eid, J., and Sollner-Webb, B. (1995) Mol. Cell. Biol. 15, 389-397) that binds
      preferentially to the C-rich strands of the subtelomere and telomere repeats. UV
      cross-linking revealed five polypeptides of ST-2 that bind directly to the G-rich
      strand of the DNA, one of which is phosphorylated. Furthermore, the presence of
      ST-1 is critical for ST-2 complex binding both to the G-rich strand and to the
      duplex DNA, evidently as part of the ST-2 complex. This indicates that when
      binding to the duplex subtelomere and telomere repeats, ST-2 may act as a protein
      bridge with its ST-1 subunit binding to the C-rich strand and its five other
      cross-linkable polypeptides binding to the G-rich strand. Such an association
      could serve to hold the genomic subtelomeric and telomeric sequences in a
      partially single-stranded configuration to facilitate the recombinational events
      in this region that are crucial to the parasite.

PMID- 9169463
TI  - 5-Azadeoxycytidine-induced chromatin remodeling of the inactive X-linked HPRT
      gene promoter occurs prior to transcription factor binding and gene reactivation.
AB  - During the process of 5-aza-2'-deoxycytidine (5aCdr)-induced reactivation of the
      X-linked human hypoxanthine phosphoribosyltransferase (HPRT) gene on the inactive
      X chromosome, acquisition of a nuclease-sensitive chromatin conformation in the
      5' region occurs before the appearance of HPRT mRNA. In vivo footprinting
      experiments reported here show that the 5aCdr-induced change in HPRT chromatin
      structure precedes the appearance of three footprints in the immediate 5'
      flanking region that are characteristic of the active HPRT allele. These and
      other data suggest the following sequence of events that lead to the reactivation
      of the HPRT gene after 5aCdr treatment: (a) hemi-demethylation of the promoter,
      (b) an "opening" of chromatin structure detectable as increased nuclease
      sensitivity, (c) transcription factor binding to the promoter, (d) assembly of
      the transcription complex, and (e) synthesis of HPRT RNA. This sequence of events
      supports the view that inactive X-linked genes are silenced by a repressive
      chromatin structure that prevents the binding of transcriptional activators to
      the promoter.

PMID- 9169465
TI  - Heme oxygenase-mediated resistance to oxygen toxicity in hamster fibroblasts.
AB  - The role of heme oxygenase (HO)-1 was evaluated in the oxygen-resistant hamster
      fibroblast cell line, O2R95, which moderately overexpress HO when compared with
      the parental cell line, HA-1. To suppress HO-1 expression, O2R95 were transfected
      with HO-1 antisense oligonucleotide or treated with tin-mesoporphyrin (SnMP). To
      increase HO-1 expression, cells were transfected with HO-1 cDNA in a
      pRC/cytomegalovirus (CMV) vector. All cells were challenged with a 48-h exposure
      to 95% O2 (hyperoxia). When HO activity was suppressed, O2R95 cells had
      significantly decreased cell viability, increased susceptibility to lipid
      peroxidation, and increased protein oxidation in hyperoxia. In contrast, further
      overexpression of HO-1 did not improve resistance to oxygen toxicity. Antisense
      transfected cells and SnMP-treated cells with lowered HO activity showed
      increased levels of cellular heme compared with controls. In the HO-1 cDNA
      transfected O2R95 cells, cellular heme was lowered compared with controls;
      however, cellular redox active iron levels were increased. We conclude that HO
      mediates cytoprotection to oxygen toxicity within a narrow range of expression.
      We speculate that this protective effect may be mediated in part through
      increased metabolism of the pro-oxidant heme but that higher levels of HO
      activity obviate protection by increased redox active iron release.

PMID- 9169466
TI  - Characterization of a phenobarbital-responsive enhancer module in mouse P450
      Cyp2b10 gene.
AB  - Induction of drug- and carcinogen-metabolizing cytochrome P450s by xenobiotic
      chemicals is a common cellular defense mechanism, usually leading to increased
      detoxification of xenobiotics but sometimes, paradoxically, to formation of more
      toxic and carcinogenic metabolites. Phenobarbital (PB) is an archetypal
      representative for chemicals including industrial solvents, pesticides, plant
      products, and clinically used drugs that induce several genes within CYP
      subfamilies 2B, 2A, 2C, and 3A in rodents and humans. Although the transcription
      of these CYP genes is activated by PB, the associated molecular mechanisms have
      not yet been elucidated. Here we have analyzed, in detail, enhancer activity of a
      far upstream region of mouse Cyp2b10 gene and report a 132-base pair PB
      responsive enhancer module (PBREM) with a 33-base pair core element containing
      binding sites for nuclear factor I- and nuclear receptor-like factors. Mutations
      of these binding sites abolish the ability of PBREM to respond to inducers in
      mouse primary hepatocytes.

PMID- 9169467
TI  - Protein kinase C-alpha activity modulates transepithelial permeability and cell
      junctions in the LLC-PK1 epithelial cell line.
AB  - Modulation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate
      (TPA) disrupts the cell-cell junctions of the epithelial cell line LLC-PK1. To
      examine the role of specific PKC isoforms in this process we have created
      modified LLC-PK1 subclones that express wild-type and dominant negative versions
      of PKC-alpha under control of the tetracycline-responsive expression system.
      Overexpression of wild-type PKC-alpha rendered the cells more sensitive to the
      effects of TPA on transepithelial permeability as measured by loss of
      transepithelial resistance across the cell sheet. Conversely, expression of a
      dominant negative PKC-alpha rendered the cells more resistant to the effects of
      TPA as measured both by loss of transepithelial resistance as well as cell
      scattering. The properties of both subclones could be modulated by the addition
      of tetracycline, which suppressed the effect of the exogenous genes. These
      results indicate that the alpha isoform of PKC is at least one of the isoforms
      that regulate tight junctions and other cell-cell junctions of LLC-PK1 epithelia.

PMID- 9169468
TI  - Regulation of human apolipoprotein A-I gene expression by gramoxone.
AB  - To induce oxidative stress, HepG2 cells were exposed to a compound known as
      gramoxone. This compound undergoes a one-electron reduction to form a stable free
      radical which is capable of generating reactive oxygen species. We demonstrated
      that exposure of HepG2 cells to gramoxone (0.1 microM) resulted in a 2-fold
      decrease in apoA-I mRNA with no significant change in apoB and apoE mRNA levels.
      To examine if increased rates of mRNA degradation were responsible for the
      reduction in apoA-I mRNA levels, mRNA half-lives were measured in the presence of
      actinomycin D with and without gramoxone treatment. These studies revealed a 4
      fold increase in the rate of apoA-I mRNA degradation in cells exposed to
      gramoxone. In similarly treated cells, nuclear run-off assays indicated that the
      transcription rate of the apoA-I gene was also increased 2-fold. Consistent with
      nuclear run-off assays, transient transfection experiments using a series of pGL2
      derived luciferase reporter plasmids containing the human apoAI proximal promoter
      demonstrated that gramoxone treatment increased apoA-I promoter activity 2-fold.
      We have identified a potential "antioxidant response element" (ARE) in the apoA-I
      promoter region that may be responsible for the increase in apoA-I
      transcriptional activity by gramoxone. Gel mobility shift assays with an ARE
      oligonucleotide revealed increased levels of a specific protein-DNA complex that
      formed with nuclear extracts from gramoxone-treated cells. UV cross-linking
      experiments with the ARE and nuclear extracts from either untreated or gramoxone
      treated cells detected proteins of approximately 100 and 115 kDa. When a single
      copy of the ARE was inserted upstream of the SV40 promoter in a luciferase
      reporter plasmid, a significant 2-fold induction in luciferase activity was
      observed in HepG2 cells in the presence of gramoxone. In contrast, a plasmid
      containing a mutant apoAI-ARE did not confer responsiveness to gramoxone.
      Furthermore, pGL2 (apoAI-250 mutant ARE), in which point mutations eliminated the
      ARE in the apoAI promoter, showed no increase in luciferase activity in response
      to gramoxone. Taken together, the data suggest that gramoxone affects apoA-I mRNA
      levels by both transcriptional and post-transcriptional mechanisms.

PMID- 9169469
TI  - Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I
      and II.
AB  - During the intraerythrocytic stage of infection, the malaria parasite Plasmodium
      falciparum digests most of the host cell hemoglobin. Hemoglobin degradation
      occurs in the acidic digestive vacuole and is essential for the survival of the
      parasite. Two aspartic proteases, plasmepsins I and II, have been isolated from
      the vacuole and shown to make the initial cleavages in the hemoglobin molecule.
      We have studied the biosynthesis of these two enzymes. Plasmepsin I is
      synthesized and processed to the mature form soon after the parasite invades the
      red blood cell, while plasmepsin II synthesis is delayed until later in
      development. Otherwise, biosynthesis of the plasmepsins is identical. The
      proplasmepsins are type II integral membrane proteins that are transported
      through the secretory pathway before cleavage to the soluble form. They are not
      glycosylated in vivo, despite the presence of several potential glycosylation
      sites. Proplasmepsin maturation appears to require acidic conditions and is
      reversibly inhibited by the tripeptide aldehydes N-acetyl-L-leucyl-L-leucyl
      norleucinal and N-acetyl-L-leucyl-L-leucyl-methional. These compounds are known
      to inhibit cysteine proteases and the chymotryptic activity of proteasomes but
      not aspartic proteases. However, proplasmepsin processing is not blocked by other
      cysteine protease inhibitors, nor by the proteasome inhibitor lactacystin.
      Processing is also not blocked by aspartic protease inhibitors. This inhibitor
      profile suggests that unlike most other aspartic proteases, proplasmepsin
      maturation may not be autocatalytic in vivo, but instead could require the action
      of an unusual processing enzyme. Compounds that block processing are expected to
      be potent antimalarials.

PMID- 9169470
TI  - Single-stranded RNA recognition by the bacteriophage T4 translational repressor,
      regA.
AB  - The T4 protein, RegA, is a translational repressor that blocks ribosome binding
      to multiple T4 messages by interacting with the mRNAs near their respective AUG
      start codons. Other than the AUG, there are no obvious similarities between the
      affected mRNAs. High affinity RNA ligands to RegA were isolated using SELEX
      (systematic evolution of ligands by exponential enrichment). The selected RNAs
      exhibited the consensus sequence 5'-AAAAUUGUUAUGUAA-3'. The AUG was invariant,
      suggesting that it is the primary effector of binding specificity. The UU
      immediately 5' to the AUG and the upstream poly(A) tract were highly conserved
      among the selected RNAs. Boundary and footprinting experiments are consistent
      with the consensus sequence defining the RegA-binding site. Interestingly,
      chemical modification and nuclease digestion data indicate that the RNA-binding
      site is single-stranded, as if RegA discriminates between targets based on their
      primary sequence, not their secondary structure. Minor variations from the
      consensus at positions other than the universally conserved AUG have little
      effect on RegA binding, but accumulation of mutations has a profound effect on
      the interaction. Comparison of the in vivo targets for RegA to the SELEX
      generated consensus suggests a repression pattern whereby the translation of
      individual messages is sequentially halted until the least similarly affected
      message, the regA gene itself, is repressed.

PMID- 9169471
TI  - Benign HEXA mutations, C739T(R247W) and C745T(R249W), cause beta-hexosaminidase A
      pseudodeficiency by reducing the alpha-subunit protein levels.
AB  - Two benign mutations, C739T(R247W) and C745T(R249W), in the alpha-subunit of beta
      hexosaminidase A (Hex A) have been found in all but one of the currently
      identified Hex A-pseudodeficient subjects. To confirm the relationship of the
      benign mutations and Hex A pseudodeficiency and to determine how the benign
      mutations reduce Hex A activity, we transiently expressed each of the benign
      mutations, and other mutations associated with infantile, juvenile, and adult
      onset forms of GM2 gangliosidosis, as Hex S (alphaalpha) and Hex A (alphabeta) in
      COS-7 cells. The benign mutations decreased the expressed Hex A and Hex S
      activity toward the synthetic substrate 4-methylumbelliferyl-6-sulfo-beta-N
      acetylglucosaminide (4-MUGS) by 60-80%, indicating that they are the primary
      cause of Hex A pseudodeficiency. Western blot analysis showed that the benign
      mutations decreased the enzymatic activity by reducing the alpha-subunit protein
      level. No change in heat sensitivity, catalytic activity, or the substrate
      specificity to the synthetic substrates, 4-methylumbelliferyl-beta-N
      acetylglucosaminide or 4-methylumbelliferyl-6-sulfo-beta-N-acetylglucosaminide,
      was detected. The effects of the benign mutations on Hex A were further analyzed
      in fibroblasts, and during transient expression, using pulse-chase metabolic
      labeling. These studies showed that the benign mutations reduced the alpha
      subunit protein by affecting its stability in vivo, not by affecting the
      processing of the alpha-subunit, i.e. phosphorylation, targeting, or secretion.
      Our studies also demonstrated that these benign mutations could be readily
      differentiated from disease-causing mutations using a transient expression
      system.

PMID- 9169472
TI  - Domain-specific interactions of human HP1-type chromodomain proteins and inner
      nuclear membrane protein LBR.
AB  - HP1-type chromodomain proteins self-associate as well as interact with the inner
      nuclear membrane protein LBR (lamin B receptor) and transcriptional coactivators
      TIF1alpha and TIF1beta. The domains of these proteins that mediate their various
      interactions have not been entirely defined. HP1-type proteins are predicted by
      hydrophobic cluster analysis to consist of two homologous but distinct globular
      domains, corresponding to the chromodomain and chromo shadow domain, separated by
      a hinge region. We show here that the chromo shadow domain mediates the self
      associations of HP1-type proteins and is also necessary for binding to LBR both
      in vitro and in the yeast two-hybrid assay. Hydrophobic cluster analysis also
      predicts that the nucleoplasmic amino-terminal portion of LBR contains two
      globular domains separated by a hinge region. The interactions of the LBR domains
      with an HP1-type protein were also analyzed by the yeast two-hybrid and in vitro
      binding assays, which showed that a portion of the second globular domain is
      necessary for binding. The modular domain organization of HP1-type proteins and
      LBR can explain some of the diverse protein-protein interactions at the chromatin
      lamina-membrane interface of the nuclear envelope.

PMID- 9169473
TI  - Transcriptional regulation of neuronal nicotinic acetylcholine receptor genes. A
      possible role for the DNA-binding protein Puralpha.
AB  - Nicotinic acetylcholine receptors constitute a multigene family (alpha2-alpha9,
      beta2-beta4) expressed in discrete temporal and spatial patterns within the
      nervous system. The receptors are critical for proper signal transmission between
      neurons and their targets. The molecular mechanisms underlying receptor gene
      expression have not been completely elucidated but clearly involve regulation at
      the level of transcription. We previously identified a novel 19-base pair (bp)
      transcriptional regulatory element in the promoter region of the rat beta4
      subunit gene. This 19-bp element interacts specifically with DNA-binding proteins
      enriched in nuclear extracts prepared from adult rat brain. Using a combination
      of cellulose-phosphate, DNA-cellulose, and DNA sequence-specific affinity
      chromatographies, we purified the 19-bp element binding activity approximately
      19,000-fold. Analysis by denaturing gel electrophoresis revealed the presence of
      four polypeptides in the most purified fraction, ranging in molecular masses
      between 31 and 114 kDa. Peptide sequence analysis revealed that one of the
      polypeptides is the bovine homologue of the transcriptional regulatory factor,
      Puralpha. Electrophoretic mobility shift assays indicated that Puralpha interacts
      directly and specifically with the 19-bp element. In addition, mobility shift
      assays using an anti-Puralpha monoclonal antibody revealed the presence of
      Puralpha, or an immunologically related protein, in nuclear extracts prepared
      from brain tissue. We hypothesize that the interaction between Puralpha and the
      19-bp element is critical for proper expression of the beta4 subunit gene.

PMID- 9169474
TI  - Protein kinase C and protein kinase A inhibit calcium-dependent but not stress
      dependent c-Jun N-terminal kinase activation in rat liver epithelial cells.
AB  - In rat liver epithelial cells (GN4), angiotensin II (Ang II) and thapsigargin
      stimulate a novel calcium-dependent tyrosine kinase (CADTK) also known as PYK2,
      CAKbeta, or RAFTK. Activation of CADTK by a thapsigargin-dependent increase in
      intracellular calcium failed to stimulate the extracellular signal-regulated
      protein kinase pathway but was well correlated with a 30-50-fold activation of c
      Jun N-terminal kinase (JNK). In contrast, Ang II, which increased both protein
      kinase C (PKC) activity and intracellular calcium, stimulated extracellular
      signal-regulated protein kinase but produced a smaller, less sustained, JNK
      activation than thapsigargin. 12-O-Tetradecanoylphorbol 13-acetate (TPA), which
      slowly activated CADTK, did not stimulate JNK. These findings suggest either that
      CADTK is not involved in JNK activation or PKC activation inhibits the CADTK to
      JNK pathway. A 1-min TPA pretreatment of GN4 cells inhibited thapsigargin
      dependent JNK activation by 80-90%. In contrast, TPA did not inhibit the >50-fold
      JNK activation effected by anisomycin or UV. The consequence of PKC-dependent JNK
      inhibition was reflected in c-Jun and c-Fos mRNA induction following treatment
      with thapsigargin and Ang II. Thapsigargin, which only minimally induced c-Fos,
      produced a much greater and more prolonged c-Jun response than Ang II. Elevation
      of another intracellular second messenger, cAMP, for 5-15 min also inhibited
      calcium-dependent JNK activation by approximately 80-90% but likewise had no
      effect on the stress-dependent JNK pathway. In summary, two pathways stimulate
      JNK in cells expressing CADTK, a calcium-dependent pathway modifiable by PKC and
      cAMP-dependent protein kinase and a stress-activated pathway independent of
      CADTK, PKC, and cAMP-dependent protein kinase; the inhibition by PKC can
      ultimately alter gene expression initiated by a calcium signal.

PMID- 9169475
TI  - Isolation and characterization of the human gp130 promoter. Regulation by STATS.
AB  - Glycoprotein 130 (gp130), a shared component of all the receptors for the
      interleukin-6 cytokine family, transduces cytokine signals in part by activating
      latent cytoplasmic signal transducers and activators of transcription (STATs).
      STATs subsequently translocate into the nucleus and stimulate gene expression. In
      the studies reported here, the 5'-flanking region of the human gp130 gene was
      isolated and the transcription initiation sites were mapped. To demonstrate that
      the isolated DNA fragment contained a functional promoter, a plasmid construct
      containing 2433 base pairs of the gp130 5'-flanking region, inserted upstream
      from the firefly luciferase gene, was transiently transfected into HepG2 hepatoma
      cells. The construct exhibited constitutive promoter activity. In addition, a 5-h
      treatment with interleukin-6 or oncostatin M stimulated the activity of this
      promoter severalfold. Localization of the cytokine response element by 5'
      deletion analysis and site-directed mutagenesis revealed a cis-acting binding
      site for activated STAT complexes. Furthermore, DNA binding analysis demonstrated
      that this element binds activated STAT1 and STAT3 homo- and heterodimers. This
      STAT-binding element was sufficient to confer cytokine stimulation to a minimal
      herpesvirus thymidine kinase promoter. These results establish that the DNA
      fragment we have isolated contains the human gp130 promoter and that interleukin
      6 type cytokines may influence the activity of this promoter via activated STATs.

PMID- 9169476
TI  - Arrestin/clathrin interaction. Localization of the clathrin binding domain of
      nonvisual arrestins to the carboxy terminus.
AB  - We have recently demonstrated that the nonvisual arrestins, beta-arrestin and
      arrestin3, interact with high affinity and stoichiometrically with clathrin, and
      we postulated that this interaction mediates internalization of G protein-coupled
      receptors (Goodman, O. B., Jr., Krupnick, J. G., Santini, F., Gurevich, V. V.,
      Penn, R. B., Gagnon, A. W., Keen, J. H., and Benovic, J. L. (1996) Nature 383,
      447-450). In this study, we localized the clathrin binding domain of arrestin3
      using a variety of approaches. Truncation mutagenesis demonstrated that the COOH
      terminal half of arrestin3 is required for clathrin interaction. Assessment of
      the clathrin binding properties of various glutathione S-transferase-arrestin3
      fusion proteins indicated that the predominant clathrin binding domain is
      contained within residues 367-385. Alanine scanning mutagenesis further localized
      this domain to residues 371-379, and site-directed mutagenesis demonstrated the
      critical importance of both hydrophobic (Leu-373, Ile-374, and Phe-376) and
      acidic (Glu-375 and Glu-377) residues in the arrestin3/clathrin interaction.
      These results are complementary to the observation that hydrophobic and basic
      residues in clathrin are critical for its interaction with nonvisual arrestins
      (Goodman, O. B. , Jr., Krupnick, J. G., Gurevich, V. V., Benovic, J. L., and
      Keen, J. H. (1997) J. Biol. Chem. 272, 15017-15022). Lastly, an arrestin3 mutant
      in which Leu-373, Ile-374, and Phe-376 were mutated to Ala was significantly
      defective in its ability to promote beta2-adrenergic receptor internalization in
      COS-1 cells when compared with wild-type arrestin3. Taken together, these results
      implicate a discrete region of arrestin3 in high affinity binding to clathrin, an
      interaction critical for agonist-promoted internalization of the beta2-adrenergic
      receptor.

PMID- 9169477
TI  - Arrestin/clathrin interaction. Localization of the arrestin binding locus to the
      clathrin terminal domain.
AB  - Previously we demonstrated that nonvisual arrestins exhibit a high affinity
      interaction with clathrin, consistent with an adaptor function in the
      internalization of G protein-coupled receptors (Goodman, O. B., Jr., Krupnick, J.
      G., Santini, F., Gurevich, V. V., Penn, R. B., Gagnon, A. W., Keen, J. H., and
      Benovic, J. L. (1996) Nature 383, 447-450). In this report we show that a short
      sequence of highly conserved residues within the globular clathrin terminal
      domain is responsible for arrestin binding. Limited proteolysis of clathrin cages
      results in the release of terminal domains and concomitant abrogation of arrestin
      binding. The nonvisual arrestins, beta-arrestin and arrestin3, but not visual
      arrestin, bind specifically to a glutathione S-transferase-clathrin terminal
      domain fusion protein. Deletion analysis and alanine scanning mutagenesis
      localize the binding site to residues 89-100 of the clathrin heavy chain and
      indicate that residues 1-100 can function as an independent arrestin binding
      domain. Site-directed mutagenesis identifies an invariant glutamine (Glu-89) and
      two highly conserved lysines (Lys-96 and Lys-98) as residues critical for
      arrestin binding, complementing hydrophobic and acidic residues in arrestin3
      which have been implicated in clathrin binding (Krupnick, J. G., Goodman, O. B.,
      Jr., Keen, J. H., and Benovic, J. L. (1997) J. Biol. Chem. 272, 15011-15016).
      Despite exhibiting high affinity clathrin binding, arrestins do not induce coat
      assembly. The terminal domain is oriented toward the plasma membrane in coated
      pits, and its binding of both arrestins and AP-2 suggests that this domain is the
      anchor responsible for adaptor-receptor recruitment to the coated pit.

PMID- 9169478
TI  - T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase
      activation.
AB  - Interleukin-2 (IL-2) is a potent T cell mitogen. However, the signaling pathways
      by which IL-2 mediates its mitogenic effect are not fully understood. One of the
      members of the mitogen-activated protein kinase (MAPK) family, p42/44MAPK
      (ERK2/1), is known to be activated by IL-2. We have now investigated the response
      to IL-2 of two other members of the MAP kinase family, p54MAP kinase (stress
      activated protein kinase (SAPK)/Jun-N-terminal kinase (JNK)) and p38MAP kinase
      (p38/Mpk2/CSBP/RK), which respond primarily to stressful and inflammatory stimuli
      (e.g. tumor necrosis factor-alpha, IL-1, and lipopolysaccharide). Here we show
      that IL-2, and another T cell growth factor, IL-7, activate both SAPK/JNK and
      p38MAP kinase. Furthermore, inhibition of p38MAP kinase activity with a specific
      pyrinidyl imidazole inhibitor SB203580 that prevents activation of its downstream
      effector, MAPK-activating protein kinase-2, correlated with suppression of IL-2-
      and IL-7-driven T cell proliferation. These data indicate that in T cells p38MAP
      kinase has a role in transducing the mitogenic signal.

PMID- 9169479
TI  - An inhibitory fragment derived from protein kinase Cepsilon prevents enhancement
      of nerve growth factor responses by ethanol and phorbol esters.
AB  - We have studied nerve growth factor (NGF)-induced differentiation of PC12 cells
      to identify PKC isozymes important for neuronal differentiation. Previous work
      showed that tumor-promoting phorbol esters and ethanol enhance NGF-induced
      mitogen-activated protein (MAP) kinase activation and neurite outgrowth by a PKC
      dependent mechanism. Ethanol also increases expression of PKCdelta and
      PKCepsilon, suggesting that one these isozymes regulates responses to NGF. To
      examine this possibility, we established PC12 cell lines that express a fragment
      encoding the first variable domain of PKCepsilon (amino acids 2-144), which acts
      as an isozyme-specific inhibitor of PKCepsilon in cardiac myocytes. Phorbol ester
      stimulated translocation of PKCepsilon was markedly reduced in these PC12 cell
      lines. In addition, phorbol ester and ethanol did not enhance NGF-induced MAP
      kinase activation or neurite outgrowth in these cells. In contrast, phorbol ester
      and ethanol increased neurite outgrowth and MAP kinase phosphorylation in cells
      expressing a fragment derived from the first variable domain of PKCdelta. These
      results demonstrate that PKCepsilon mediates enhancement of NGF-induced signaling
      and neurite outgrowth by phorbol esters and ethanol in PC12 cells.

PMID- 9169480
TI  - The T cell-directed CC chemokine TARC is a highly specific biological ligand for
      CC chemokine receptor 4.
AB  - Thymus and activation-regulated chemokine (TARC) is a recently identified CC
      chemokine that is expressed constitutively in thymus and transiently in
      stimulated peripheral blood mononuclear cells. TARC functions as a selective
      chemoattractant for T cells that express a class of receptors binding TARC with
      high affinity and specificity. To identify the receptor for TARC, we produced
      TARC as a fusion protein with secreted alkaline phosphatase (SEAP) and used it
      for specific binding. By stably transfecting five orphan receptors and five known
      CC chemokine receptors (CCR1 to -5) into K562 cells, we found that TARC-SEAP
      bound selectively to cells expressing CCR4. TARC-SEAP also bound to K562 cells
      stably expressing CCR4 with a high affinity (Kd = 0.5 nM). Only TARC and not five
      other CC chemokines (MCP-1 (monocyte chemoattractant protein-1), RANTES
      (regulated upon activation, normal T cells expressed and secreted), MIP-1alpha
      (macrophage inflammatory protein-1alpha), MIP-1beta, and LARC (liver and
      activation-regulated chemokine)) competed with TARC-SEAP for binding to CCR4.
      TARC but not RANTES or MIP-1alpha induced migration and calcium mobilization in
      293/EBNA-1 cells stably expressing CCR4. K562 cells stably expressing CCR4 also
      responded to TARC in a calcium mobilization assay. Northern blot analysis
      revealed that CCR4 mRNA was expressed strongly in human T cell lines and
      peripheral blood T cells but not in B cells, natural killer cells, monocytes, or
      granulocytes. Taken together, TARC is a specific functional ligand for CCR4, and
      CCR4 is the specific receptor for TARC selectively expressed on T cells.

PMID- 9169481
TI  - Out on first.

PMID- 9169482
TI  - Psickle, the temporary leaky link between sickling and cellular dehydration.

PMID- 9169483
TI  - Perspectives series: cell adhesion in vascular biology. Adhesive interactions of
      sickle erythrocytes with endothelium.

PMID- 9169484
TI  - Perspectives series: host/pathogen interactions. Dynamics of HIV-1 replication in
      vivo.

PMID- 9169485
TI  - In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset
      obesity.
AB  - A decreased mobilization of triglycerides may contribute to fat accumulation in
      adipocytes, leading to obesity. However, this hypothesis remains to be proven. In
      this study, epinephrine-induced lipid mobilization was investigated in vivo in
      nine markedly obese children (160+/-5% ideal body weight) aged 12.1+/-0.1 yr
      during the dynamic phase of fat deposition, compared with six age-matched
      nonobese children. As an in vivo index of lipolysis, we measured glycerol flux
      using a nonradioactive tracer dilution approach, and plasma free fatty acid
      concentrations. In the basal state, the obese children had a 30% lower rate of
      glycerol release per unit fat mass than the lean children. To study the
      regulation of lipolysis, epinephrine was infused stepwise at fixed doses of 0.75
      and then 1. 50 microg/min in both groups. In lean children, glycerol flux and
      plasma free fatty acid increased to an average of 249-246% of basal values,
      respectively, in response to a mean plasma epinephrine of 396+/-41 pg/ml. The
      corresponding increase was only 55-72% in the obese children, although their mean
      plasma epinephrine reached 606+/-68 pg/ml. All obese and nonobese children,
      except an Arg64Trp heterozygote, were homozygotes for Trp at position 64 of their
      beta3-adrenoreceptor. The resistance of lipolysis to epinephrine showed no
      relationship with the Arg64 polymorphism of the beta3-adrenoreceptor gene. In
      summary, in vivo lipolysis, which mostly reflects the mobilization of lipid
      stores from subcutaneous adipose tissue, shows a decreased sensitivity to
      epinephrine in childhood onset obesity. Since our study was carried out in obese
      children during the dynamic phase of fat accumulation, the observed resistance to
      catecholamines might possibly be causative rather than the result of obesity.

PMID- 9169487
TI  - A synthetic peptide inhibitor for alpha-chemokines inhibits the growth of
      melanoma cell lines.
AB  - Melanoma growth stimulatory activity (MGSA/GROalpha) is a 73 amino acid peptide
      sharing sequence characteristics with the alpha-chemokine superfamily.
      MGSA/GROalpha is produced by diverse melanoma cell lines and reported to act as
      an autocrine growth factor for the cells. We tested the binding of MGSA/GROalpha
      to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could
      bind to MGSA/GROalpha but not to interleukin-8. Recently, we defined a novel
      hexapeptide, antileukinate, which is a potent inhibitor of binding of alpha
      chemokines to their receptors on neutrophils. When antileukinate was added to
      melanoma cells, it inhibited the binding of MGSA/ GROalpha. The growth of cells
      from both melanoma cell lines was suppressed completely in the presence of 100
      microM peptide. The cell growth inhibition was reversed by the removal of the
      peptide from the culture media or by the addition of the excess amount of
      MGSA/GROalpha. The viability of Hs 294T cells in the presence of 100 microM
      peptide was > 92%. These findings suggest that MGSA/GROalpha is an essential
      autostimulatory growth factor for melanoma cells and antileukinate inhibits their
      growth by preventing MGSA/GROalpha from binding to its receptors.

PMID- 9169486
TI  - Inactivation of Streptococcus pyogenes extracellular cysteine protease
      significantly decreases mouse lethality of serotype M3 and M49 strains.
AB  - Cysteine proteases have been implicated as important virulence factors in a wide
      range of prokaryotic and eukaryotic pathogens, but little direct evidence has
      been presented to support this notion. Virtually all strains of the human
      bacterial pathogen Streptococcus pyogenes express a highly conserved
      extracellular cysteine protease known as streptococcal pyrogenic exotoxin B
      (SpeB). Two sets of isogenic strains deficient in SpeB cysteine protease activity
      were constructed by integrational mutagenesis using nonreplicating recombinant
      plasmids containing a truncated segment of the speB gene. Immunoblot analyses and
      enzyme assays confirmed that the mutant derivatives were deficient in expression
      of enzymatically active SpeB cysteine protease. To test the hypothesis that the
      cysteine protease participates in host mortality, we assessed the ability of
      serotype M3 and M49 wild-type strains and isogenic protease-negative mutants to
      cause death in outbred mice after intraperitoneal inoculation. Compared to wild
      type parental organisms, the serotype M3 speB mutant lost virtually all ability
      to cause mouse death (P < 0.00001), and similarly, the virulence of the M49
      mutant was detrimentally altered (P < 0.005). The data unambiguously demonstrate
      that the streptococcal enzyme is a virulence factor, and thereby provide
      additional evidence that microbial cysteine proteases are critical in host
      pathogen interactions.

PMID- 9169488
TI  - Surface expression, polarization, and functional significance of CD73 in human
      intestinal epithelia.
AB  - During active intestinal inflammation polymorphonuclear leukocytes (PMN)
      transmigrate into the lumen and release 5'-AMP (J. Clin. Invest. 1993. 91:2320
      2325). 5'-AMP is converted to adenosine by the apical epithelial surface with
      subsequent activation of electrogenic Cl- secretion (the basis of secretory
      diarrhea) via apical A2b adenosine receptors (J. Biol. Chem. 1995. 270:2387
      2394). Using a polarized human intestinal epithelial monolayer (T84), we now
      characterize the basis of the observed conversion of 5'-AMP to adenosine required
      for this paracrine signaling pathway. An inhibitor of the ecto-5'-nucleotidase
      CD73, alpha, beta-methylene ADP (AOPCP), inhibited epithelial Cl- secretory
      responses to 5'-AMP, but not to authentic adenosine. Confocal immunofluorescent
      microscopy revealed CD73 to be surface expressed on both model and natural human
      intestinal epithelia. Expression was about sixfold greater on the apical cell
      surface as assessed biochemically by selective cell surface biotinylation, and
      morphologically by immunofluorescence. Treatment with phosphotidylinositol
      specific-phospholipase C (PI-PLC) released 95% of apical CD73, indicating that
      the intestinal CD73 possesses a glycosylphosphatidylinositol (GPI) anchor.
      Neither adenosine nor 5'-AMP stimulation induced intact T84 cells to shed surface
      CD73. The bulk of apical CD73 ( approximately 60%) was released from the cell
      surface by treatment with 1% Triton X-100 (TX-100) at 4 degrees C, but such
      release was not affected by pretreatment with ligand or by prior, antibody
      mediated cross-linking of CD73. Subsequent analyses showed that the subpool of
      CD73 released by TX-100 at 4 degrees C was not truly solubilized, but rather
      represented TX-100-induced release of CD73-containing membrane fragments. These
      membrane fragments displayed light density on sucrose gradients characteristic of
      detergent insoluble glycosphingolipid-rich membrane domains (DIGs)/ caveolae,
      were solubilized by n-octyl glucoside (NOG, 1%) at 4 degrees C, and contained
      caveolin. These data indicate that human intestinal epithelia express CD73, which
      is apically polarized and targeted to microdomains with DIGs/caveolae
      characteristics. CD73 likely participates in translating paracrine, PMN-derived
      5'-AMP signals to the authentic effector adenosine. These studies define CD73 as
      central to PMN-mediated intestinal Cl- secretion, the major directacting
      mechanism by which PMN induce intestinal epithelial Cl- secretion.

PMID- 9169490
TI  - Transcriptional control in keratinocytes and fibroblasts using synthetic ligands.
AB  - The skin is an attractive tissue for regulated target gene expression by virtue
      of its accessibility to topical regulating stimuli. We have used synthetic ligand
      driven intracellular oligomerization to accomplish specific target gene
      regulation in human skin keratinocytes and fibroblasts. GAL4 DNA binding domains
      and VP16 transactivation domains, each linked to the FK506 binding protein, were
      expressed in normal human skin keratinocytes and fibroblasts. These hybrid
      proteins underwent heterodimerization via the novel intracellular dimerizing
      agent FK1012 to generate a heterodimeric activator of target gene expression in
      vitro. Dimeric FK1012, but not monomeric FK506M induced target gene expression in
      a dose-dependent fashion. FK1012 exerted no detectable nonspecific effects on
      expression of cutaneous genes and did not alter cellular proliferation kinetics.
      Controlled oligomerization of hybrid transcription activators offers a potential
      approach to target gene regulation in cells of normal human skin.

PMID- 9169489
TI  - ATP-sensitive potassium channels mediate contraction-induced attenuation of
      sympathetic vasoconstriction in rat skeletal muscle.
AB  - Sympathetic vasoconstriction is sensitive to inhibition by metabolic events in
      contracting rat and human skeletal muscle, but the underlying cellular mechanisms
      are unknown. In rats, this inhibition involves mainly alpha2-adrenergic
      vasoconstriction, which relies heavily on Ca2+ influx through voltage-dependent
      Ca2+ channels. We therefore hypothesized that contraction-induced inhibition of
      sympathetic vasoconstriction is mediated by ATP-sensitive potassium (KATP)
      channels, a hyperpolarizing vasodilator mechanism that could be activated by some
      metabolic product(s) of skeletal muscle contraction. We tested this hypothesis in
      anesthetized rats by measuring femoral artery blood flow responses to lumbar
      sympathetic nerve stimulation or intraarterial hindlimb infusion of the specific
      alpha2-adrenergic agonist UK 14,304 during KATP channel activation with diazoxide
      in resting hindlimb and during KATP channel block with glibenclamide in
      contracting hindlimb. The major new findings are twofold. First, like muscle
      contraction, pharmacologic activation of KATP channels with diazoxide in resting
      hindlimb dose dependently attenuated the vasoconstrictor responses to either
      sympathetic nerve stimulation or intraarterial UK 14,304. Second, the large
      contraction-induced attenuation in sympathetic vasoconstriction elicited by nerve
      stimulation or UK 14,304 was partially reversed when the physiologic activation
      of KATP channels produced by muscle contraction was prevented with glibenclamide.
      We conclude that contraction-induced activation of KATP channels is a major
      mechanism underlying metabolic inhibition of sympathetic vasoconstriction in
      exercising skeletal muscle.

PMID- 9169491
TI  - Expression of bacterial superantigen genes in mice induces localized mononuclear
      cell inflammatory responses.
AB  - Bacterial superantigens are potent T cell activators, and superantigen proteins
      have been injected into mice and other animals to study T cell responses in vivo.
      When superantigen proteins are injected, however, the T cell stimulatory effects
      cannot be confined to specific tissues. Therefore, to target superantigen
      expression to specific tissues, we used gene transfer techniques to express
      bacterial superantigen genes in mammalian cells in vitro and in tissues in vivo.
      Murine, human, and canine cells transfected with superantigen genes in vitro all
      produced superantigen proteins both intracellularly and extracellularly, as
      assessed by bioassay, immunocytochemistry, and antigen ELISA. Superantigens
      produced by transfected eukaryotic cells retained their biologic specificity for
      T cell receptor binding. Intramuscular injection of superantigen plasmid DNA in
      vivo induced an intense intramuscular mononuclear cell infiltrate, an effect that
      could not be reproduced by intramuscular injection of superantigen protein.
      Intradermal and intravenous injection of superantigen DNA induced cutaneous and
      intrapulmonary mononuclear cell inflammatory responses, respectively. Thus,
      superantigen genes can be expressed by mammalian cells in vivo. Superantigen gene
      therapy represents a novel method of targeting localized T cell inflammatory
      reactions, with potential application to treatment of cancer and certain
      infectious diseases.

PMID- 9169492
TI  - Nitric oxide synthase lies downstream from vascular endothelial growth factor
      induced but not basic fibroblast growth factor-induced angiogenesis.
AB  - Systemic administration of the nitric oxide (NO) synthase inhibitor Nomega-nitro-
      arginine methyl ester (L-NAME) to rabbits bearing a corneal implant blocked
      vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor
      (bFGF)-induced angiogenesis. L-NAME completely blocked angiogenesis induced by
      VEGF-transfected MCF-7 breast carcinoma cells and the cells remained dormant in
      the cornea. Postcapillary endothelial cell migration and growth induced by VEGF
      were blocked by both the NO synthase inhibitor Nomega-mono-methyl--arginine and
      by the guanylate cyclase inhibitor LY 83583. We conclude that NO is a downstream
      imperative of VEGF-, but not bFGF-induced angiogenesis, and propose that the NO
      synthase/guanylate cyclase pathway is a potential target for controlling tumor
      angiogenesis in response to VEGF. Our studies support recent evidence that VEGF
      and bFGF induce angiogenesis by different mechanistic pathways using the
      alphavbeta5 and alphavbeta3 integrins, respectively.

PMID- 9169493
TI  - p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes.
AB  - Myocyte cell loss is a prominent and important pathogenic feature of cardiac
      ischemia. We have used cultured neonatal rat cardiac myocytes exposed to
      prolonged hypoxia as an experimental system to identify critical factors involved
      in cardiomyocyte death. Exposure of myocytes to hypoxia for 48 h resulted in
      intranucleosomal cleavage of genomic DNA characteristic of apoptosis and was
      accompanied by increased p53 transactivating activity and protein accumulation.
      Expression of p21/WAF-1/CIP-1, a well-characterized target of p53
      transactivation, also increased in response to hypoxia. Hypoxia did not cause DNA
      laddering or cell loss in cardiac fibroblasts. To determine whether the increase
      in p53 expression in myocytes was sufficient to induce apoptosis, normoxic
      cultures were infected with a replication-defective adenovirus expressing wild
      type human p53 (AdCMV.p53). Infected cells expressed high intracellular levels of
      p53 protein and exhibited the morphological changes and genomic DNA fragmentation
      characteristic of apoptosis. In contrast, no genomic DNA fragmentation was
      observed in myocytes infected with the control virus lacking an insert
      (AdCMV.null) or in cardiac fibroblasts infected with AdCMV.p53. These results
      suggest that the intracellular signaling pathways activated by p53 might play a
      critical role in the regulation of hypoxia-induced apoptosis of cardiomyocytes.

PMID- 9169494
TI  - Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation
      in transgenic mice.
AB  - D-type cyclin/cyclin-dependent kinase (CDK) complexes regulate transit through
      the restriction point of the cell cycle, and thus are required for the initiation
      of DNA synthesis. Transgenic mice which overexpress cyclin D1 in the heart were
      produced to determine if D-type cyclin deregulation would alter myocardial
      development. Cyclin D1 overexpression resulted in a concomitant increase in CDK4
      levels in the adult myocardium, as well as modest increases in proliferating cell
      nuclear antigen and CDK2 levels. Flow cytometric and morphologic analyses of
      dispersed cell preparations indicated that the adult transgenic cardiomyocytes
      had abnormal patterns of multinucleation. Histochemical analyses confirmed a
      marked increase in number of cardiomyocyte nuclei in sections prepared from the
      transgenic mice as compared with those from control animals. Tritiated thymidine
      incorporation analyses revealed sustained cardiomyocyte DNA synthesis in adult
      transgenic hearts.

PMID- 9169495
TI  - Anticoagulant synergism of heparin and activated protein C in vitro. Role of a
      novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V
      by activated protein C.
AB  - Interactions between standard heparin and the physiological anticoagulant plasma
      protein, activated protein C (APC) were studied. The ability of heparin to
      prolong the activated partial thromboplastin time and the factor Xa- one-stage
      clotting time of normal plasma was markedly enhanced by addition of purified APC
      to the assays. Experiments using purified clotting factors showed that heparin
      enhanced by fourfold the phospholipid-dependent inactivation of factor V by APC.
      In contrast to factor V, there was no effect of heparin on inactivation of
      thrombin-activated factor Va by APC. Based on SDS-PAGE analysis, heparin enhanced
      the rate of proteolysis of factor V but not factor Va by APC. Coagulation assays
      using immunodepleted plasmas showed that the enhancement of heparin action by APC
      was independent of antithrombin III, heparin cofactor II, and protein S.
      Experiments using purified proteins showed that heparin did not inhibit factor V
      activation by thrombin. In summary, heparin and APC showed significant
      anticoagulant synergy in plasma due to three mechanisms that simultaneously
      decreased thrombin generation by the prothrombinase complex. These mechanisms
      include: first, heparin enhancement of antithrombin III-dependent inhibition of
      factor V activation by thrombin; second, the inactivation of membrane-bound FVa
      by APC; and third, the proteolytic inactivation of membrane-bound factor V by
      APC, which is enhanced by heparin.

PMID- 9169497
TI  - Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E
      null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by
      effects on apolipoprotein E.
AB  - The mechanism of apolipoprotein (apo) CIII-induced hypertriglyceridemia remains
      uncertain. We crossed apoCIII transgenic and apoE gene knockout (apoE0) mice, and
      observed severe hypertriglyceridemia with plasma triglyceride levels of 4,521+/
      6, 394 mg/dl vs. 423+/-106 mg/dl in apoE0 mice, P < 0.00001 for log(triglycerides
      [TG]). Cholesterols were 1,181+/-487 mg/dl vs. 658+/-151 mg/dl, P < 0.0001.
      Lipoprotein fractionation showed a marked increase in triglyceride-enriched
      chylomicrons+VLDL. This increase was limited to the lowest density (chylomicrons
      and Sf 100-400) subfractions. Intermediate density lipoproteins (IDL)+LDL
      increased moderately, and HDL decreased. There was no significant increase in
      triglyceride production in apoCIII transgenic/apoE0 mice. The clearance of VLDL
      triglycerides, however, was significantly decreased. Lipoprotein lipase in
      postheparin plasma was elevated, but activation studies suggested LPL inhibition
      by both apoCIII transgenic and apoCIII transgenic/apoE0 plasma. ApoCIII
      overexpression also produced a marked decrease in VLDL glycosaminoglycan binding
      which was independent of apoE. The predominant mechanism of apoCIII-induced
      hypertriglyceridemia appears to be decreased lipolysis at the cell surface. The
      altered lipoprotein profile that was produced also allowed us to address the
      question of the direct atherogenicity of chylomicrons and large VLDL.
      Quantitative arteriosclerosis studies showed identical results in both apoCIII
      transgenic/apoE0 and apoE0 mice, supporting the view that very large triglyceride
      enriched particles are not directly atherogenic.

PMID- 9169496
TI  - Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon
      beta-1b therapy.
AB  - Costimulatory molecules help determine T cell responses. CD80 (B7-1) and CD86 (B7
      2), costimulatory proteins on antigen-presenting cells, bind to CD28 on T cells.
      When costimulation is coupled with a signal through the T cell receptor (TCR), T
      cell proliferation and cytokine secretion are induced. However, TCR signaling
      without CD80/CD86CD28 costimulation causes anergy. During multiple sclerosis (MS)
      exacerbations, circulating immune cells are activated, Th1 cytokine levels in the
      blood are elevated, and blood-derived immune cells destroy brain oligodendroglia.
      In the experimental autoimmune encephalomyelitis model of MS, CD80 on antigen
      presenting cells induces Th1 cell responses; CD86 enhances generation of Th2
      cells. Variation in CD80 and CD86 expression is likely to influence immune
      regulation in MS. We demonstrate that the number of circulating CD80(+)
      lymphocytes is increased significantly during MS exacerbations, but is normal in
      stable MS. These CD80(+) lymphocytes are predominantly B cells, based on two
      color flow cytometry. The number of CD71(+) and HLA-DR+ lymphocytes and monocytes
      is also increased in active MS. Therapy with IFN beta-1b markedly reduces the
      number of circulating CD80(+) B cells and increases CD86(+) monocyte number. HLA
      DR+, CD71(+), and CD25(+) mononuclear cell numbers are also reduced by therapy.
      The number of CD80(+) cells may be a useful surrogate marker during IFN-beta
      therapy, and reduction of CD80-mediated costimulation may be one therapeutic
      mechanism by which IFN-beta acts in MS.

PMID- 9169498
TI  - The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat
      kidney. Inhibition by a soluble P-selectin ligand.
AB  - Ischemia/reperfusion (I/R) injury associated with renal transplantation may
      influence both early graft function and late changes. The initial (</= 7 d)
      events of warm and in situ perfused cold ischemia of native kidneys in
      uninephrectomized rats were examined. mRNA expression of the early adhesion
      molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells
      and macrophages entered the injured kidney by 2-5 d; the associated upregulation
      of MHC class II antigen expression suggested increased immunogenicity of the
      organ. Th1 products (IL-2, TNFalpha, IFNgamma) and macrophage-associated products
      (IL-1, IL-6, TGFbeta) remained highly expressed after 2 d. To examine directly
      the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand
      (sPSGL) was used. Ischemic kidneys were perfused in situ with 5 microg of sPSGL
      in UW solution; 50 microg was administered intravenously 3 h after reperfusion. E
      selectin mRNA remained at baseline, leukocytes did not infiltrate the injured
      organs throughout the 7-d period, and their associated products were markedly
      inhibited. Class II expression did not increase. No renal dysfunction secondary
      to I/R occurred. The early changes of I/R injury may be prevented by treatment
      with soluble P- and E-selectin ligand. This may reduce subsequent host
      inflammatory responses after transplantation.

PMID- 9169499
TI  - Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent
      angiogenic factor.
AB  - The presence of mast cells near capillary sprouting sites suggests an association
      between mast cells and angiogenesis. However, the role of mast cells in blood
      vessel development remains to be defined. In an attempt to elucidate this
      relationship, we investigated the effect of human mast cells (HMC-1) and their
      products on human dermal microvascular endothelial cell (HDMEC) tube formation.
      Coculture of HMC-1 with HDMEC led to a dose-response increase in the network area
      of vascular tube growth. Moreover, the extent of neovascularization was enhanced
      greatly when HMC-1 were degranulated in the presence of HDMEC. Further
      examination using antagonists to various mast cell products revealed a blunted
      response (73-88% decrease) in the area of vascular tube formation if specific
      inhibitors of tryptase were present. Tryptase (3 microg/ml) directly added to
      HDMEC caused a significant augmentation of capillary growth, which was suppressed
      by specific tryptase inhibitors. Tryptase also directly induced cell
      proliferation of HDMEC in a dose-dependent fashion (2 pM-2 nM). Our results
      suggest that mast cells act at sites of new vessel formation by secreting
      tryptase, which then functions as a potent and previously unrecognized angiogenic
      factor.

PMID- 9169500
TI  - Early effects of iodine deficiency on radial glial cells of the hippocampus of
      the rat fetus. A model of neurological cretinism.
AB  - The most severe brain damage associated with thyroid dysfunction during
      development is observed in neurological cretins from areas with marked iodine
      deficiency. The damage is irreversible by birth and related to maternal
      hypothyroxinemia before mid gestation. However, direct evidence of this
      etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine
      content (LID), or LID supplemented with KI. Other rats were fed the breeding diet
      with a normal iodine content plus a goitrogen, methimazole (MMI). The
      concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were
      determined in the brain of 21-d-old fetuses. The proportion of radial glial cell
      fibers expressing nestin and glial fibrillary acidic protein was determined in
      the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the
      LID and MMI fetuses, as compared to their respective controls. The number of
      immature glial cell fibers, expressing nestin, was not affected, but the
      proportion of mature glial cell fibers, expressing glial fibrillary acidic
      protein, was significantly decreased by both LID and MMI treatment of the dams.
      These results show impaired maturation of cells involved in neuronal migration in
      the hippocampus, a region known to be affected in cretinism, at a stage of
      development equivalent to mid gestation in humans. The impairment is related to
      fetal cerebral thyroid hormone deficiency during a period of development when
      maternal thyroxinemia is believed to play an important role.

PMID- 9169501
TI  - cGMP-stimulated cyclic nucleotide phosphodiesterase regulates the basal calcium
      current in human atrial myocytes.
AB  - EHNA (Erythro-9-[2-hydroxy-3-nonyl]adenine) is a wellknown inhibitor of adenosine
      deaminase. Recently, EHNA was shown to block the activity of purified soluble
      cGMPstimulated phosphodiesterase (PDE2) from frog, human, and porcine heart with
      an apparent Ki value of approximately 1 microM and with negligible effects on
      Ca2+/calmodulin PDE (PDE1), cGMP-inhibited PDE (PDE3), and low Km cAMP-specific
      PDE (PDE4) (Mery, P.F., C. Pavoine, F. Pecker, and R. Fischmeister. 1995. Mol.
      Pharmacol. 48:121-130; Podzuweit, T., P. Nennstiel, and A. Muller. 1995. Cell.
      Signalling. 7:733- 738). To investigate the role of PDE2 in the regulation of
      cardiac L-type Ca2+ current (ICa), we have examined the effect of EHNA on ICa in
      freshly isolated human atrial myocytes. Extracellular application of 0.1-10
      microM EHNA induced an increase in the amplitude of basal ICa ( approximately 80%
      at 1 microM) without modification of the current-voltage or inactivation curves.
      The maximal stimulatory effect of EHNA on ICa was comparable in amplitude with
      the maximal effect of isoprenaline (1 microM), and the two effects were not
      additive. The effect of EHNA was not a result of adenosine deaminase inhibition,
      since 2'-deoxycoformycin (1-30 microM), another adenosine deaminase inhibitor
      with no effect on PDE2, or adenosine (1-10 microM) did not increase ICa. In the
      absence of intracellular GTP, the substrate of guanylyl cyclase, EHNA did not
      increase ICa. However, under similar conditions, intracellular perfusion with 0.5
      microM cGMP produced an 80% increase in ICa. As opposed to human cardiomyocytes,
      EHNA (1-10 microM) did not modify ICa in isolated rat ventricular and atrial
      myocytes. We conclude that basal ICa is controlled by PDE2 activity in human
      atrial myocytes. Both PDE2 and PDE3 may contribute to keep the cyclic nucleotides
      concentrations at minimum in the absence of adenylyl and/or guanylyl cyclase
      stimulation.

PMID- 9169502
TI  - Circumferential deformation and shear stress induce differential responses in
      saphenous vein endothelium exposed to arterial flow.
AB  - Adaptation of saphenous vein to the hemodynamic stresses of the arterial
      circulation is critical to the maturation of vein bypass grafts. We have
      investigated early adaptive responses of venous endothelium by placing excised
      human saphenous vein in a bypass circuit with either venous or arterial flow
      conditions, using external stenting to resolve the effects of longitudinal
      (shear) from circumferential stress. Endothelial protein concentrations were
      assessed by immunostaining area (ratio of protein/CD31) and Western blotting of
      endothelial cell lysates (staining ratio protein/vWf). In both unstented and
      stented veins nitric oxide synthase increased after 90 min of arterial flow:
      twofold increase of immunostaining area (P = 0.001), four- to fivefold increase
      by Western blotting (P = 0.02), and increased A23187mediated maximum endothelium
      dependent relaxation of vein rings (P = 0.01). In unstented veins, ICAM-1
      concentration was increased after 45 min of arterial flow: twofold increase by
      immunostaining (P = 0.001) and Western blotting (P = 0.038), with maximum
      fibrinogen-mediated endothelium-dependent relaxation increasing from 55.9+/-4.9
      to 97+/-2.1% (P = 0.01). In contrast, in unstented veins there was a threefold
      decrease of VCAM-1 and no change in P-selectin after arterial flow for 45 and 90
      min, respectively. However, no changes in ICAM-1 and VCAM-1 were observed in
      stented veins. The flow-induced alterations in nitric oxide synthase, ICAM-1, and
      VCAM-1 were abolished when 3 mM tetraethylammonium ion (K+ channel blocker) was
      included in the vein perfusate. The very rapid changes in ICAM-1 and VCAM-1
      expression are a response to circumferential stress, whereas the slower
      upregulation of nitric oxide synthase is a response to longitudinal (shear)
      stress. Similar changes could influence the adhesiveness of endothelium in newly
      implanted saphenous vein bypass grafts.

PMID- 9169503
TI  - Stochastic nature and red cell population distribution of the sickling-induced
      Ca2+ permeability.
AB  - To explore basic properties of the sickling-induced cation permeability pathway,
      the Ca2+ component (Psickle-Ca) was studied in density-fractionated sickle cell
      anemia (SS) discocytes through its effects on the activity of the cells'
      Ca2+sensitive K+-channels (KCa). The instant state of KCa channel activation was
      monitored during continuous or cyclic deoxygenation of the cells using a novel
      thiocyanate-densecell formation method. Each deoxy pulse caused a reversible,
      sustained Psickle-Ca, which activated KCa channels in only 10-45% of cells at
      physiological [Ca2+]o ("activated cells"). After removal of cells activated by
      each previous deoxy pulse, subsequent pulses generated similar activated cell
      fractions, indicating a random determination rather than the response of a
      specific vulnerable subpopulation. The fraction of activated cells rose
      monotonically with [Ca2+]o along a curve reflecting the cells' distribution of
      Psickle-Ca, with values high enough in a small cell fraction to trigger near
      maximal KCa channels. Consistent with the stochastic nature of Psickle-Ca,
      repeated deoxygenated-oxygenated pulsing led to progressive dense cell formation,
      whereas single long pulses caused one early density shift. Thus deoxygenation
      induced Ca2+-permeabilization in SS cells is a probabilistic event with large
      cumulative dehydrating potential. The possible molecular nature of Psickle-Ca is
      discussed.

PMID- 9169504
TI  - Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked
      by tilt.
AB  - The pathophysiology of neurally mediated syncope is poorly understood. It has
      been widely assumed that excessive sympathetic activation in a setting of left
      ventricular hypovolemia stimulates ventricular afferents that trigger hypotension
      and bradycardia. We tested this hypothesis by determining if excessive
      sympathetic activation precedes development of neurally mediated syncope, and if
      this correlates with alterations in baroreflex function. We studied the changes
      in intraarterial blood pressure (BP), heart rate (HR), central venous pressure
      (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked
      by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1
      episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy
      subjects who consistently experienced syncope during tilt (FS+, n = 20).
      Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were
      obtained after infusions of phenylephrine and sodium nitroprusside. Compared to
      CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed
      by a progressive decrease and ultimately complete disappearance of MSNA with
      syncope. SYN patients also had attenuation of norepinephrine increases and lower
      baroreflex slope sensitivity, both during tilt and after pharmacologic testing.
      FS+ subjects had the largest decrease in CVP with tilt and had significant
      increases in MSNA and heart rate baroreflex slopes. These data challenge the view
      that excessive generalized sympathetic activation is the precursor of the
      hemodynamic abnormality underlying recurrent neurally mediated syncope.

PMID- 9169505
TI  - Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated
      cytotoxicity.
AB  - Myonuclear apoptosis is an early event in the pathology of dystrophin-deficient
      muscular dystrophy in the mdx mouse. However, events that initiate apoptosis in
      muscular dystrophy are unknown, and whether elimination of apoptosis can
      ameliorate subsequent muscle wasting remains a major question. We have tested the
      hypothesis that cytotoxic T-lymphocytes initiate myonuclear apoptosis in
      dystrophic muscle, and examined whether perforin-mediated cytotoxicity plays a
      role in the pathophysiology of muscular dystrophy. Mdx mice showed muscle
      invasion by cytotoxic T cells and helper T cells at the onset of histologically
      detectable muscle fiber pathology. At this time, perforin-expressing cells were
      also present at elevated concentration. Mdx mice depleted of CD8(+) cells showed
      a significant reduction of apoptotic myonuclei concentration and a reduction in
      necrosis, judged by macrophage invasion of muscle fibers. Double-mutant mice,
      deficient in dystrophin and perforin, showed nearly complete absence of
      myonuclear apoptosis, and a significant reduction in the concentration of
      macrophages in the connective tissue surrounding muscle fibers. However, muscle
      fiber invasion by macrophages was not reduced significantly in double mutant
      mice. Thus, cytotoxic T-lymphocytes contribute significantly to apoptosis and
      necrosis in mdx dystrophy, and perforin-mediated killing is primarily responsible
      for myonuclear apoptosis.

PMID- 9169506
TI  - IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.
AB  - The early colocalization of T cells and the potent immunostimulatory cytokine IFN
      gamma to atherosclerotic lesions suggest that the immune system contributes to
      atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0
      mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this
      process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional
      IFN-gamma, was documented in apoE 0 atheromata. Then, the apoE 0 mice were
      crossed with IFN-gamma receptor (IFNgammaR) 0 mice to generate apoE 0/IFNgammaR 0
      mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a
      substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion
      lipid accumulation, a decrease in lesion cellularity, but a marked increase in
      lesion collagen content. Evaluation of the plasma lipoproteins showed that the
      compound knockout mice had a marked increase in potentially atheroprotective
      phospholipid/apoA-IV rich particles as well. This correlated with an induction of
      hepatic apoA-IV transcripts. These observations suggest that IFN-gamma promotes
      and modifies atherosclerosis through both local effects in the arterial wall as
      well as a systemic effect on plasma lipoproteins. Therefore, therapeutic
      inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor
      and stable atheromata.

PMID- 9169507
TI  - EGF receptor activation stimulates endogenous gastrin gene expression in canine G
      cells and human gastric cell cultures.
AB  - Gastrin release from the antral gastrin-expressing cell (G cell) is regulated by
      bombesin and luminal factors. Yet, these same extracellular regulators do not
      stimulate expression of the gene. Since the gastric mucosa expresses large
      quantities of EGF receptor ligands such as TGFalpha, we examined whether EGF
      receptor ligands stimulate gastrin gene expression in gastrin-expressing cell
      cultures. EGF receptor activation of primary cultures stimulated gastrin gene
      expression about twofold; whereas bombesin treatment of antral G cell cultures
      stimulated gastrin release but not gene expression. EGF and TGFalpha were weak
      stimulants of gastrin release. EGF receptor activation of AGS human gastric
      adenocarcinoma cell line stimulated gastrin gene expression nearly fourfold; and
      gastrin reporter constructs transfected into AGS cells were stimulated more than
      fourfold by EGF. EGF induction was conferred by the previously defined GC-rich
      gastrin EGF response element (gERE) element located at -68 to -53 bp upstream
      from the cap site since a mutation of the gERE element abolished both basal and
      EGF induction. Moreover, EGF treatment of AGS cells stimulated binding of the
      transcription factor Sp1 to this element. Collectively, these results demonstrate
      that gastrin gene expression and gastrin release are regulated by different
      signaling pathways: gene expression by EGF receptor activation and gastrin
      secretion by neuropeptides and luminal factors.

PMID- 9169508
TI  - Angiotensin II depolarizes podocytes in the intact glomerulus of the Rat.
AB  - The aim of this study was to examine the effects of angiotensin II (Ang II) on
      cellular functions of rat podocytes (pod) in the intact freshly isolated
      glomerulus and in culture. Membrane voltage (Vm) and ion currents of pod were
      examined with the patch clamp technique in fast whole cell and whole cell
      nystatin configuration. Vm of pod was -38+/-1 mV (n = 86). Ang II led to a
      concentration-dependent depolarization of pod with an ED50 of 10(-8) mol/liter.
      In the presence of Ang II (10(-7) mol/liter, n = 20), pod depolarized by 7+/-1
      mV. In an extracellular solution with a reduced Cl- concentration of 32
      mmol/liter, the effect of Ang II on Vm was significantly increased to 14+/-4 mV
      (n = 8). The depolarization induced by Ang II was neither inhibited in an
      extracellular Na+-free solution nor in a solution with a reduced extracellular
      Ca2+ (down to 1 micromol/liter). Like Ang II, the calcium ionophore A23187 (10(
      5) mol/liter, n = 9) depolarized pod by 10+/-2 mV, whereas forskolin (10(-5)
      mol/liter), 8-(4-chlorophenylthio)-cAMP and N2,2'-o-dibutyryl-cGMP (both 5 x 10(
      4) mol/liter) did not alter Vm of pod. The angiotensin 1 receptor antagonist
      losartan (10(-7) mol/liter) completely inhibited the Ang II-induced (10(-7)
      mol/liter) depolarization (n = 5). Like pod in the glomerulus, pod in short term
      culture depolarized in response to Ang II (10(-8) mol/liter, n = 5). Our results
      suggest that Ang II depolarizes podocytes directly by opening a Cl- conductance.
      The activation of this ion conductance is mediated by an AT1 receptor and may be
      regulated by the intracellular Ca2+ activity.

PMID- 9169509
TI  - A minimal role for selectins in the recruitment of leukocytes into the inflamed
      liver microvasculature.
AB  - A two-step paradigm for leukocyte recruitment has been established in a number of
      tissues including the mesentery, skin, and muscle, and necessitates an initial
      rolling step via the selectins before firm leukocyte adhesion via the integrins.
      In view of the many inflammatory diseases that involve the liver, we investigated
      the importance of rolling and the selectins in the hepatic microvasculature and
      compared the responses to that of the commonly used mesentery or cremaster
      microvasculature. We visualized the liver microvasculature using intravital
      microscopy and we determined that within the liver the majority of leukocytes
      adhere within the sinusoids (80%) in response to a chemotactic stimulus such as
      FMLP (20% in postsinusoidal venules) whereas leukocytes adhere exclusively within
      postcapillary venules in tissue like the mouse cremaster. In the sinusoids, the
      adhesive response to FMLP is not dependent upon selectins inasmuch as adhesion
      was not reduced in the sinusoidal vessels of P-selectin-deficient mice or E
      selectin/P-selectin- deficient animals in the presence or absence of L-selectin
      antibody. No rolling or adhesion was detected in response to FMLP in the selectin
      deficient cremaster microvasculature. Immunoneutralization of selectins with
      fucoidan in wildtype mice eliminated rolling and adhesion in the cremaster but
      failed to affect adhesion in the liver sinusoids in response to FMLP. More long
      term leukocyte recruitment with lipopolysaccharide (4 h) was also impaired in the
      cremaster but not the liver microvasculature in selectin-deficient animals.
      Leukocyte adhesion in the sinusoids was reduced in P-selectin-deficient mice also
      lacking intercellular adhesion molecule-1 (ICAM-1). This study for the first time
      demonstrates that selectins are not an essential step for leukocyte recruitment
      into the inflamed liver microvasculature.

PMID- 9169510
TI  - Role of ouabain-like compound in the rostral ventrolateral medulla in rats.
AB  - To determine whether ouabain-like compound (OLC) exerts modulatory influences on
      the activity of vasomotor neurons in the rostral ventrolateral medulla (RVLM), we
      examined the effects of microinjecting ouabain, digoxin-specific antibody Fab
      fragments, and mAb against ouabain on the rat RVLM. Microinjection of ouabain
      into the unilateral RVLM of anesthetized normotensive rats elicited dose
      dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve
      activity (RSNA). The pressor and sympathoexcitatory effects of ouabain in the
      RVLM were reversed by microinjections of an M2 muscarinic antagonist, gallamine,
      or digoxin-specific antibody Fab fragments. Furthermore, a prior microinjection
      in the RVLM of gallamine, digoxinspecific antibody Fab fragments, or kainic acid
      or intravenous injection of hexamethonium all prevented the pressor and
      sympathoexcitatory effects induced by a subsequent microinjection of ouabain.
      Microinjections of either digoxinspecific antibody Fab fragments or gallamine per
      se significantly decreased baseline MAP and RSNA. Injection of digoxin-specific
      antibody Fab fragments attenuated the effects of a subsequent injection of
      gallamine. Microinjection of mAb against ouabain, but not nonspecific IgG, also
      significantly decreased baseline MAP and RSNA. These results suggest that OLC in
      the RVLM contributes to the tonic activity of vasomotor neurons in anesthetized
      normotensive rats, and the action of OLC in the RVLM is at least partly mediated
      by M2 muscarinic mechanisms.

PMID- 9169512
TI  - Resurgent sodium current and action potential formation in dissociated cerebellar
      Purkinje neurons.
AB  - Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje
      neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive
      inward current was elicited when the membrane was repolarized to voltages between
      -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal
      inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed
      with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the
      resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had
      no such current. The current may reflect recovery of inactivated channels through
      open states, because in Purkinje neurons (but not CA3 neurons) there was partial
      recovery from inactivation at -40 mV, coinciding with the rise of resurgent
      current. In single-channel recordings, individual channels gave openings
      corresponding to resurgent and conventional transient current. Action potentials
      were recorded from dissociated neurons under current clamp to investigate the
      role of the resurgent current in action potential formation. Purkinje neurons
      fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented
      spontaneous firing, and brief depolarization then induced all-or-none firing of
      conglomerate action potentials comprising three to four spikes. When conglomerate
      action potentials were used as command voltages in voltage-clamp experiments, TTX
      sensitive sodium current was elicited between spikes. The falling phase of an
      action potential is similar to voltage patterns that activate resurgent sodium
      current, and thus, resurgent sodium current likely contributes to the formation
      of conglomerate action potentials in Purkinje neurons.

PMID- 9169511
TI  - Endogenous adenosine mediates the presynaptic inhibition induced by aglycemia at
      corticostriatal synapses.
AB  - Energy deprivation, as a result of aglycemia, leads to depression of the central
      synaptic transmission. Endogenous adenosine has been implicated in this
      depressant effect. We have studied the possible involvement of endogenous
      adenosine in the depression of corticostriatal excitatory transmission induced by
      glucose deprivation by using intracellular recordings in brain slices. After
      stimulation of corticostriatal fibers, EPSPs were recorded from striatal spiny
      neurons. Adenosine (3-300 microM) or brief periods (5-10 min) of aglycemia
      reduced the EPSP amplitude but did not alter the membrane potential and the
      resistance of the recorded cells. These inhibitory effects were not associated
      with an alteration of the postsynaptic sensitivity to exogenous glutamate but
      were coupled with an increased paired-pulse facilitation, suggesting the
      involvement of presynaptic mechanisms. A delayed postsynaptic membrane
      depolarization/inward current was detected after 15-20 min of glucose
      deprivation. The presynaptic inhibitory effects induced by adenosine and
      aglycemia were both antagonized either by the nonselective adenosine receptor
      antagonist caffeine (2.5 mM) or by the A1 receptor antagonists 8-cyclopentyl-1,3
      dimethylxanthine (CPT, 1 microM) and 1,3-dipropyl-8-cyclopentylxanthine (CPX, 300
      nM). Conversely, these antagonists affected neither the delayed membrane
      depolarization/inward current nor the underlying conductance increase produced by
      glucose deprivation. The ATP-sensitive potassium channel blockers tolbutamide (1
      mM) and glipizide (100 nM) had no effect on the aglycemia-induced decrease of
      EPSP amplitude. Our data demonstrate that endogenous adenosine acting on A1
      receptors mediates the presynaptic inhibition induced by aglycemia at
      corticostriatal synapses, whereas ATP-dependent potassium channels do not play a
      significant role in this presynaptic inhibition.

PMID- 9169514
TI  - Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2
      receptors.
AB  - Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing
      of motor information received from the cortex. Disruption of the D2R gene
      function in mice results in a severe locomotor impairment. This phenotype has
      analogies with Parkinson's disease symptoms. D2R-null mice were used to
      investigate the role of this receptor in the generation of striatal synaptic
      plasticity. Tetanic stimulation of corticostriatal fibers produced long-term
      depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly,
      recordings from D2R-null mice showed the converse: long-term potentiation (LTP).
      This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium
      free medium, LTP was also revealed in WT mice and found to be enhanced by L
      sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R
      agonist. In D2R-null mice this modulation was lost. Thus, our study indicates
      that D2Rs play a key role in mechanisms underlying the direction of long-term
      changes in synaptic efficacy in the striatum. It also shows that an imbalance
      between D2R and NMDA receptor activity induces altered synaptic plasticity at
      corticostriatal synapses. This abnormal synaptic plasticity might cause the
      movement disorders observed in Parkinson's disease.

PMID- 9169513
TI  - Brain-derived neurotrophic factor mediates the activity-dependent regulation of
      inhibition in neocortical cultures.
AB  - The excitability of cortical circuits is modulated by interneurons that release
      the inhibitory neurotransmitter GABA. In primate and rodent visual cortex,
      activity deprivation leads to a decrease in the expression of GABA. This suggests
      that activity is able to adjust the strength of cortical inhibition, but this has
      not been demonstrated directly. In addition, the nature of the signal linking
      activity to GABA expression has not been determined. Activity is known to
      regulate the expression of the neurotrophin brain-derived neurotrophic factor
      (BDNF), and BDNF has been shown to influence the phenotype of GABAergic
      interneurons. We use a culture system from postnatal rat visual cortex to test
      the hypothesis that activity is regulating the strength of cortical inhibition
      through the regulation of BDNF. Cultures were double-labeled against GABA and the
      neuronal marker MAP2, and the percentage of neurons that were GABA-positive was
      determined. Blocking spontaneous activity in these cultures reversibly decreased
      the number of GABA-positive neurons without affecting neuronal survival. Voltage
      clamp analysis of inhibitory currents demonstrated that activity blockade also
      decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal
      neuron firing rates. All of these effects were prevented by incubation with BDNF
      during activity blockade, but not by neurotrophin 3 or nerve growth factor.
      Additionally, blockade of neurotrophin signaling mimicked the effects of activity
      blockade on GABA expression. These data suggest that activity regulates cortical
      inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an
      important role in the control of cortical excitability.

PMID- 9169515
TI  - Structural abnormalities and deficient maintenance of peripheral nerve myelin in
      mice lacking the gap junction protein connexin 32.
AB  - Mutations affecting the connexin 32 (Cx32) gene are associated with the X-linked
      form of the hereditary peripheral neuropathy Charcot-Marie-Tooth disease (CMTX).
      We show that Cx32-deficient mice develop a late-onset progressive peripheral
      neuropathy with abnormalities comparable to those associated with CMTX, thus
      providing proof of the critical role of Cx32 in the maintenance of peripheral
      nerve myelin and an animal model for CMTX. Frequently observed features include
      abnormally thin myelin sheaths, cellular onion bulb formation reflecting myelin
      degeneration-induced Schwann cell proliferation, and enlarged periaxonal collars
      while nerve conductance properties are altered only slightly. These observations
      are consistent with earlier hypotheses suggesting a function of Cx32 as a channel
      forming protein that facilitates the communication between the abaxonal and
      adaxonal aspects of Schwann cell cytoplasm.

PMID- 9169516
TI  - Neuronal dopamine subpopulations maintained in hypothalamic slice explant
      cultures exhibit distinct tyrosine hydroxylase mRNA turnover rates.
AB  - Changes in mRNA stability have been shown to regulate critical intracellular
      processes. In this investigation, we studied tyrosine hydroxylase (TH) mRNA
      turnover in functionally and anatomically distinct dopaminergic (DA) populations
      of the rat hypothalamus. To this end, long-term slice explant cultures from
      postnatal, preoptic area/hypothalami, containing three anatomically discrete DA
      populations, were generated and maintained under defined conditions. The
      organotypic cultures were treated with the transcription inhibitors 5,6-dichloro
      1-D-ribofuranosylbenzimidazole or actinomycin D and processed for in situ
      hybridization histochemistry. Relative TH mRNA content per cell was quantitated.
      Single-cell analysis showed marked differences in basal TH mRNA turnover rates
      between DA neuronal populations. Anterior and midhypothalamic DA neurons
      exhibited half-time turnovers of 9-12 and 11-23 hr, respectively. In contrast, in
      the caudal hypothalamus, DA neurons of the arcuate nucleus had a significantly
      lower baseline level and more rapid turnover (6-7 hr) of TH mRNA. This
      investigation shows that basal turnover of a phenotypic mRNA, TH mRNA in DA
      neurons, is not an intrinsic property of the phenotypic marker. Furthermore, we
      found that destabilization of TH mRNA in the caudal hypothalamus corresponds to
      the known rhythmic output displayed by arcuate DA cells and, as such, may be
      critical for normal function of this population. We propose that intrinsic
      differences in the post-transcriptional regulation of TH permits neuronal
      subpopulations, which subserve different physiological functions, an additional
      mechanism to control DA biosynthesis in response to their unique needs.

PMID- 9169517
TI  - Sensitivity to jerky gene dosage underlies epileptic seizures in mice.
AB  - Animals with one deleted jerky allele are more susceptible to chemically induced
      seizures than wild-type mice and display recurrent behavioral seizures. The
      phenotype of these hemizygotes is characterized by no apparent neurological
      symptoms other than recurrent seizures reminiscent of human idiopathic epilepsy.
      The jerky gene encodes a 60 kDa protein resembling a number of DNA-binding
      proteins. Here, we show that the jerky gene is expressed in all tissues examined,
      including brain, liver, lung, spleen, testis, and ovary, and study an apparent
      paradox of how an allelic deletion of the ubiquitously expressed jerky gene can
      lead to hyperexcitability and seizures but not to other symptoms. We demonstrate
      that jerky has a dosage-sensitive function (haploinsufficiency) in brain and that
      this sensitivity to reduced jerky dosage could explain the occurrence of seizures
      in hemizygotes. However, jerky has a nondosage-sensitive function as well,
      because the total absence of jerky in homozygotes results in abnormalities of
      somatic and sexual development. A number of idiopathic epilepsies are dominantly
      inherited, such as benign familial neonatal convulsions, juvenile myoclonic
      epilepsy, as well as benign epilepsy with centrotemporal spikes, and the
      pathomechanism of these epilepsies may be based on haploinsufficiency in the
      brain.

PMID- 9169518
TI  - Comparison of N- and P/Q-type voltage-gated calcium channel current inhibition.
AB  - Activation of N- and P/Q-type voltage-gated calcium channels triggers
      neurotransmitter release at central and peripheral synapses. These channels are
      targets for regulatory mechanisms, including inhibition by G-protein-linked
      receptors. Inhibition of P/Q-type channels has been less well studied than the
      extensively characterized inhibition of N-type channels, but it is thought that
      they are inhibited by similar mechanisms although possibly to a lesser extent
      than N-type channels. The aim of this study was to compare the inhibition of the
      two channel types. Calcium currents were recorded from adrenal chromaffin cells
      and isolated by the selective blockers omega-conotoxin GVIA (1 microM) and omega
      agatoxin IVA (400 nM). The inhibition was elicited by ATP (100 microM) or
      intracellular application of GTP-gamma-S. It was classified as voltage-sensitive
      (relieved by a conditioning prepulse) or voltage-insensitive (present after a
      conditioning prepulse). The voltage-insensitive inhibition accounted for a 20%
      reduction of both currents, whereas the voltage-sensitive inhibition reduced the
      N-type current by 45% but the P/Q-type current by 18%. However, the voltage
      dependence of the inhibition, the time course of relief from inhibition during a
      conditioning prepulse, and the time course of reinhibition after such a prepulse
      showed few differences between the N- and P/Q-type channels. Assuming a simple
      bimolecular reaction, our data suggest that changes in the kinetics of the G
      protein/channel interaction alone cannot explain the differences in the
      inhibition of the N- and P/Q-type calcium channels. The subtle differences in
      inhibition may facilitate the selective regulation of neurotransmitter release.

PMID- 9169519
TI  - Control of NMDA receptor activation by a glycine transporter co-expressed in
      Xenopus oocytes.
AB  - We present evidence that membrane transporters can control the membrane
      receptor's agonist concentration in restricted extracellular spaces of a
      biological model. The model is constructed by co-expressing glycine/Na/Cl
      cotransporters (GLYT1b) and NMDA receptors (NMDARs) (composed of the subunits NR1
      and NR2A or NR2B) in Xenopus oocytes. We use the high-affinity glycine site of
      the NMDARs as a sensor of the actual juxtamembrane glycine concentration. We show
      that glycine uptake by GLYT1b dramatically reduces NMDAR currents by reducing the
      glycine concentration in extracellular spaces in which diffusion is restricted.
      This effect appears only in oocytes in which GLYT1b and NMDAR are co-expressed.
      It is Na+- and voltage-dependent, and is abolished when Na+ is replaced by Li+
      and when glycine is replaced by D-serine (a coagonist of the NMDAR that is not
      transported by GLYT1b). These results demonstrate the ability of the GLYT
      transporter to reduce glycine concentration at the level of NMDARs in restricted
      diffusion spaces. This observation could account for a prevalent role of membrane
      transporters in the modulation of synapse transmission in the CNS. From a more
      general point of view, our results draw attention to possible significant
      discrepancies between local concentrations at the level of substrate targets in
      biological membranes and their concentration in the bulk solution when membrane
      transporters are present.

PMID- 9169520
TI  - Identification of estrogen-responsive genes in neuroblastoma SK-ER3 cells.
AB  - To evaluate the role of estrogen receptor in the differentiation of cells of
      neural origin, we developed a molecular approach aimed at the identification of
      estrogen target genes by mRNA differential display PCR (ddPCR) in human
      neuroblastoma SK-ER3 cells. More than 3000 RNAs were examined, a few of which
      displayed a differential regulation pattern in response to 17beta-estradiol (E2).
      Sequence analysis of three differentially amplified ddPCR products showed
      homology with the growth-associated nuclear protein prothymosin-alpha (PTMA), the
      Bcl2-interacting protein Nip2, and one mRNA previously described by others in
      fetal human brain. Two ddPCR products, referred to as P4 and P10, corresponded to
      new DNA sequences. Northern analysis confirmed that estrogen treatment of SK-ER3
      cells resulted in the upregulation and downregulation of expression of these
      messages. In particular, PTMA was found to accumulate at both 1 and 17 hr after
      E2 treatment, whereas P10 product accumulated only at 1 hr. Conversely, P4, Nip2,
      and the fetal brain-related mRNAs were significantly decreased by the treatment.
      Further time course analysis of PTMA and Nip2 mRNAs levels indicated that the
      hormone exerted a marked biphasic regulatory effect on expression of both
      messages during the course of cell differentiation. In the present study we
      report for the first time the identification of a panel of estrogen target genes
      in neural cells that provide new insights in the molecular mechanism of action of
      E2 in cells of neural origin.

PMID- 9169521
TI  - Postsynaptic calcineurin activity downregulates synaptic transmission by
      weakening intracellular Ca2+ signaling mechanisms in hippocampal CA1 neurons.
AB  - Protein phosphorylation and dephosphorylation are believed to functionally couple
      neuronal activity and synaptic plasticity. Our previous results indicated that
      postsynaptic Ca2+/calmodulin (CaM) signaling pathways play an important role in
      setting synaptic strength, and calcineurin (CaN) activity limits synaptic
      responses during basal synaptic transmission and long-term potentiation
      expression. The inhibition of postsynaptic CaN activity by FK-506 or an
      autoinhibitory peptide induced synaptic potentiation in hippocampal slices, which
      occludes tetanus-induced LTP. FK-506-induced synaptic potentiation was expressed
      in adult but not young rats. To elucidate mechanisms underlying CaN-inhibited
      synaptic potentiation, we co-injected certain agents affecting Ca2+ signaling
      pathways with CaN inhibitors into CA1 neurons. Synaptic potentiation induced by
      FK-506 was significantly attenuated by co-injecting BAPTA, heparin/dantrolene
      (inhibitors of intracellular Ca2+ release), a CaM-binding peptide, or CaM-KII/PKC
      pseudosubstrate peptides. These results indicate that postsynaptic CaN activity
      can downregulate evoked synaptic transmission by weakening intracellular Ca2+
      signals and downstream protein kinase activities.

PMID- 9169522
TI  - Calcium homeostasis and reactive oxygen species production in cells transformed
      by mitochondria from individuals with sporadic Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with defects in mitochondrial function.
      Mitochondrial-based disturbances in calcium homeostasis, reactive oxygen species
      (ROS) generation, and amyloid metabolism have been implicated in the
      pathophysiology of sporadic AD. The cellular consequences of mitochondrial
      dysfunction, however, are not known. To examine these consequences,
      mitochondrially transformed cells (cybrids) were created from AD patients or
      disease-free controls. Mitochondria from platelets were fused to rho0 cells
      created by depleting the human neuroblastoma line SH-SY5Y of its mitochondrial
      DNA (mtDNA). AD cybrids demonstrated a 52% decrease in electron transport chain
      (ETC) complex IV activity but no difference in complex I activity compared with
      control cybrids or SH-SY5Y cells. This mitochondrial dysfunction suggests a
      transferable mtDNA defect associated with AD. ROS generation was elevated in the
      AD cybrids. AD cybrids also displayed an increased basal cytosolic calcium
      concentration and enhanced sensitivity to inositol-1,4, 5-triphosphate (InsP3)
      mediated release. Furthermore, they recovered more slowly from an elevation in
      cytosolic calcium induced by the InsP3 agonist carbachol. Mitochondrial calcium
      buffering plays a major role after this type of perturbation. beta-amyloid (25
      35) peptide delayed the initiation of calcium recovery to a carbachol challenge
      and slowed the recovery rate. Nerve growth factor reduced the carbachol-induced
      maximum and moderated the recovery kinetics. Succinate increased ETC activity and
      partially restored the AD cybrid recovery rate. These subtle alterations in
      calcium homeostasis and ROS generation might lead to increased susceptibility to
      cell death under circumstances not ordinarily toxic.

PMID- 9169523
TI  - Expression of specific tubulin isotypes increases during regeneration of injured
      CNS neurons, but not after the application of brain-derived neurotrophic factor
      (BDNF).
AB  - Axonal regrowth after injury is accompanied by changes in the expression of
      tubulin, but the contributions of substrate molecules and neurotrophic factors in
      regulating these changes in vivo are not known. Adult rat retinal ganglion cells
      (RGCs) were examined after intraorbital axotomy, after application of a
      peripheral nerve (PN) graft to stimulate regeneration, and after axotomy and
      treatment with brain-derived neurotrophic factor (BDNF). After these treatments
      we used in situ hybridization to study mRNA levels for betaI, betaII, betaIII,
      betaIVa, and Talpha1 tubulin isotypes. Levels of mRNA for all isotypes were
      downregulated after intraorbital axotomy. During regrowth of injured RGC axons,
      mRNA levels for betaII, betaIII, and Talpha1 isotypes were upregulated
      specifically and dramatically, suggesting that elevated expression of these
      isotypes is correlated specifically with axonal regrowth. A corresponding
      increase in betaIII protein levels was detected by immunocytochemistry. The betaI
      and betaIVa mRNAs were not increased during regeneration. BDNF did not elicit a
      specific increase in the mRNA levels for the betaIII and Talpha1 isotypes and had
      only a small effect on mRNA levels for the betaII isotype. Therefore, despite the
      ability of BDNF to support the survival of injured RGCs and to enhance neurite
      outgrowth of retinal neurons in vitro, the in vivo application of BDNF alone is
      unable to induce the program of changes in growth-associated tubulins that
      accompany regeneration of RGC axons into PN grafts. We speculate that, in
      addition to BDNF, cooperative signaling with substrate molecules is required to
      allow RGCs to regenerate and exhibit tubulin isotype switching.

PMID- 9169524
TI  - Differential susceptibility to neurotoxicity mediated by neurotrophins and
      neuronal nitric oxide synthase.
AB  - NMDA neurotoxicity, which is mediated, in part, by formation of nitric oxide (NO)
      via activation of neuronal NO synthase (nNOS), is modulated by neurotrophins.
      nNOS expression in rat and mouse primary neuronal cultures grown on a glial
      feeder layer is significantly less than that of neurons grown on a polyornithine
      (Poly-O) matrix. Neurotrophins markedly increase the number of nNOS neurons, nNOS
      protein, and NOS catalytic activity and enhance NMDA neurotoxicity via NO
      dependent mechanisms when neurons are grown on glial feeder layers. In contrast,
      when rat or mouse primary cortical neurons are grown on a Poly-O matrix,
      neurotrophins have no influence on nNOS neuronal number or NOS catalytic activity
      and reduce NMDA neurotoxicity. Primary neuronal cultures from mice lacking nNOS
      grown on a glial feeder layer fail to respond to neurotrophin-mediated
      enhancement of neurotoxicity. Together, these results indicate that nNOS
      expression and NMDA NO-mediated neurotoxicity are dependent, in part, on the
      culture paradigm, and neurotrophins regulate the susceptibility to NMDA
      neurotoxicity via modulation of nNOS. Furthermore, these results support the idea
      that NMDA neurotoxicity in culture is critically dependent on the developmental
      state of the neurons being assessed and suggest that, when cortical neurons are
      cultured on a glial feeder layer, they do not reach nearly as mature a phenotype
      as when grown on a Poly-O matrix.

PMID- 9169525
TI  - Tenascin-R is an intrinsic autocrine factor for oligodendrocyte differentiation
      and promotes cell adhesion by a sulfatide-mediated mechanism.
AB  - O4(+) oligodendrocyte (OL) progenitors in the mammalian CNS are committed fully
      to terminal differentiation into myelin-forming cells. In the absence of other
      cell types in vitro, OL differentiation reproduces the in vivo development with a
      correct timing, suggesting the existence of an intrinsic regulatory mechanism
      that presently is unknown. We have examined the effect of two isoforms of the
      extracellular matrix (ECM) molecule tenascin-R (TN-R), which is expressed by OLs
      during the process of myelination, on the adhesion and maturation of OLs in
      vitro. Here we show that the substrate-bound molecules supported the adhesion of
      O4(+) OLs independently of the CNS region or age from which they were derived. At
      the molecular level this process was mediated by protein binding to membrane
      surface sulfatides (Sulf), as indicated by the interference of O4 antibody and
      Sulf with the attachment of OLs or other Sulf+ cells, erythrocytes, to TN-R
      substrates and by direct protein-glycolipid binding studies. In the absence of
      platelet-derived growth factor (PDGF), exogenous TN-R induced myelin gene
      expression and the upregulation of its own synthesis by cultured cells, resulting
      in a rapid terminal differentiation of O4(+) progenitors. Our findings strongly
      suggest that TN-R represents an intrinsic regulatory molecule that controls the
      timed OL differentiation by an autocrine mechanism and imply the relevance of TN
      R for CNS myelination and remyelination.

PMID- 9169526
TI  - Identification and functional characterization of a K+ channel alpha-subunit with
      regulatory properties specific to brain.
AB  - The physiological diversity of K+ channels mainly depends on the expression of
      several genes encoding different alpha-subunits. We have cloned a new K+ channel
      alpha-subunit (Kv2.3r) that is unable to form functional channels on its own but
      that has a major regulatory function. Kv2.3r can coassemble selectively with
      other alpha-subunits to form functional heteromultimeric K+ channels with kinetic
      properties that differ from those of the parent channels. Kv2.3r is expressed
      exclusively in the brain, being concentrated particularly in neocortical neurons.
      The functional expression of this regulatory alpha-subunit represents a novel
      mechanism without precedents in voltage-gated channels, which might contribute to
      further increase the functional diversity of K+ channels necessary to specify the
      intrinsic electrical properties of individual neurons.

PMID- 9169528
TI  - Transporters buffer synaptically released glutamate on a submillisecond time
      scale.
AB  - The role of transporters in clearing free glutamate from the synaptic cleft was
      studied in rat CA1 hippocampal neurons cultured on glial microislands. The time
      course of free glutamate in the cleft during a synaptic event was estimated by
      measuring the extent to which the rapidly dissociating AMPA receptor antagonist
      kynurenate (KYN) was replaced by glutamate during a synaptic response. Dose
      inhibition of the AMPA receptor EPSC by KYN was less than predicted by the
      equilibrium affinity of the antagonist, and the rise time of AMPA receptor
      miniature EPSCs (mEPSCs) was slowed by KYN. Both results indicated that KYN
      dissociated from AMPA receptors and was replaced by synaptically released
      transmitter. When transporters were blocked by D,L-threo-beta-hydroxyaspartic
      acid (THA) or Li+, the mEPSC rise time in the presence of KYN was slowed further,
      indicating that transporters affect the glutamate concentration in the first few
      hundred microseconds of the synaptic response. The glutamate transient necessary
      to cause these effects was determined by developing a detailed kinetic model of
      the AMPA receptor. The model replicated the effects of KYN on the amplitude and
      rise time of the synaptic responses when driven by glutamate transients that were
      similar to previous estimates (; ). The effects of THA were replicated by slowing
      and enlarging the slower phase of the dual component transient by about 20% or by
      prolonging the single component by almost 40%. Because transport is too slow to
      account for these effects, it is concluded that transporters buffer glutamate in
      the synaptic cleft.

PMID- 9169527
TI  - Heterozygous peripheral myelin protein 22-deficient mice are affected by a
      progressive demyelinating tomaculous neuropathy.
AB  - Hereditary neuropathy with liability to pressure palsy (HNPP) is associated with
      a heterozygous 1.5 megabase deletion on chromosome 17 that includes the
      peripheral myelin protein (PMP) gene PMP22. We show that heterozygous PMP22 knock
      out mice, which carry only one functional pmp22 allele and thus genetically mimic
      HNPP closely, display similar morphological and electrophysiological features as
      observed in HNPP nerves. As reported previously, focal hypermyelinating
      structures called tomacula, the pathological hallmarks of HNPP, develop
      progressively in young PMP22(+/0) mice. By following the fate of tomacula during
      aging, we demonstrate now that these mutant animals are also interesting models
      for examining HNPP disease mechanisms. Subtle electrophysiological abnormalities
      are detected in PMP22(+/0) mice >1 year old, and a significant number of
      abnormally swollen and degenerating tomacula are present. Thinly myelinated axons
      and supernumerary Schwann cells forming onion bulbs as fingerprints of repeated
      cycles of demyelination and remyelination are also encountered frequently.
      Quantitative analyses using electron microscopy on cross sections and light
      microscopy on single teased nerve fibers suggest that tomacula are intrinsically
      unstable structures that are prone to degeneration; however, the severity of
      morphological and electrophysiological abnormalities in PMP22(+/0) mice is
      variable. These combined findings are reminiscent of the disease progression in
      HNPP and offer a possible explanation about why some HNPP patients develop a
      chronic motor and sensory neuropathy later in life that resembles demyelinating
      forms of Charcot-Marie-Tooth disease by both morphological and clinical criteria.

PMID- 9169529
TI  - Endogenous serine protease inhibitor modulates epileptic activity and hippocampal
      long-term potentiation.
AB  - Protease nexin-1 (PN-1), a member of the serpin superfamily, controls the
      activity of extracellular serine proteases and is expressed in the brain. Mutant
      mice overexpressing PN-1 in brain under the control of the Thy-1 promoter (Thy
      1/PN-1) or lacking PN-1 (PN-1-/-) were found to develop epileptic activity in
      vivo and in vitro. Theta burst-induced long-term potentiation (LTP) and NMDA
      receptor-mediated synaptic transmission in the CA1 field of hippocampal slices
      were augmented in Thy 1/PN-1 mice and reduced in PN-1-/- mice. Compensatory
      changes in GABA-mediated inhibition in Thy 1/PN-1 mice suggest that altered brain
      PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic
      transmission.

PMID- 9169530
TI  - The shaking-B2 mutation disrupts electrical synapses in a flight circuit in adult
      Drosophila.
AB  - The shaking-B2 mutation was used to analyze synapses between haltere afferents
      and a flight motoneuron in adult Drosophila. We show that the electrical synapses
      among many neurons in the flight circuit are disrupted in shaking-B2 flies,
      suggesting that shaking-B expression is required for electrical synapses
      throughout the nervous system. In wild-type flies haltere afferents are dye
      coupled to the first basalar motoneuron, and stimulation of these afferents
      evokes electromyograms from the first basalar muscle with short latencies. In
      shaking-B2 flies dye coupling between haltere afferents and the motoneuron is
      abolished, and afferent stimulation evokes electromyograms at abnormally long
      latencies. Intracellular recordings from the motoneuron confirm that the site of
      the defect in shaking-B2 flies is at the synapses between haltere afferents and
      the flight motoneuron. The nicotinic cholinergic antagonist mecamylamine blocks
      the haltere-to-flight motoneuron synapses in shaking-B2 flies but does not block
      those synapses in wild-type flies. Together, these results show that the haltere
      to-flight motoneuron synapses comprise an electrical component that requires
      shaking-B and a chemical component that is likely to be cholinergic.

PMID- 9169531
TI  - An ATP-dependent inwardly rectifying potassium channel, KAB-2 (Kir4. 1), in
      cochlear stria vascularis of inner ear: its specific subcellular localization and
      correlation with the formation of endocochlear potential.
AB  - Cochlear endolymph has a highly positive potential of approximately +80 mV. This
      so-called endocochlear potential (EP) is essential for hearing. Although pivotal
      roles of K+ channels in the formation of EP have been suggested, the types and
      distribution of K+ channels in cochlea have not been characterized. Because EP
      was depressed by vascular perfusion of Ba2+, an inhibitor of inwardly rectifying
      K+ (Kir) channels, but not by either 4-aminopyridine or tetraethylammonium, we
      examined the expression of Kir channel subunits in cochlear stria vascularis, the
      tissue that is supposed to play the central role in the generation of positive
      EP. Of 11 members of the Kir channel family examined with reverse transcription
      PCR, we could detect only expression of KAB-2 (Kir4.1) mRNA in stria vascularis.
      KAB-2 immunoreactivity was specifically localized at the basolateral membrane of
      marginal cells but not in either basal or intermediate cells. Developmental
      expression of KAB-2 in marginal cells paralleled formation of EP. Furthermore,
      deaf mutant mice (viable dominant spotting; WV/WV) expressed no KAB-2 in their
      marginal cells. These results suggest that KAB-2 in marginal cells may be
      critically involved in the generation of positive EP.

PMID- 9169532
TI  - RNA transport in dendrites: a cis-acting targeting element is contained within
      neuronal BC1 RNA.
AB  - In nerve cells, a select group of RNAs has been localized to dendritic domains.
      Here we have examined dendritic RNA transport in sympathetic neurons in primary
      culture, using a microinjection protocol with neuronal BC1 RNA and with BC1
      derived sequence segments. After cytoplasmic microinjection, full-length BC1 RNA
      was selectively transported to dendrites; in contrast, control RNAs such as
      nuclear RNAs and random-sequence irrelevant RNAs remained restricted to
      cytoplasmic areas proximal to the injection sites. Chimeric RNAs were constructed
      that contained the full-length BC1 sequence inserted upstream or downstream of
      the coding regions of nondendritic mRNAs. After microinjection, such chimeric
      RNAs were specifically targeted to dendrites; microinjected corresponding
      nonchimeric mRNAs were not. Dendritic transport of BC1 RNA was rapid: the average
      dendritic delivery rate within the first hour after microinjection was 242 +/- 25
      microm/hr. Whereas a 5'-BC1 segment of 62 nucleotides was transported to
      dendrites to extents and at levels similar to full-length BC1 RNA, a 3'-BC1
      segment of 60 nucleotides did not exit injected somata to any significant degree.
      A cis-acting dendritic targeting element is thus contained in the 5' part of
      neuronal BC1 RNA. These results demonstrate that mechanisms exist in neurons for
      fast and specific transport of selected RNAs to dendrites.

PMID- 9169533
TI  - Neurexin is expressed on nerves, but not at nerve terminals, in the electric
      organ.
AB  - Neurexins are highly variable transmembrane proteins hypothesized to be nerve
      terminal-specific cell adhesion molecules. As a test of the hypothesis that
      neurexin is restricted to the nerve terminal, we examined neurexins in the
      electric organ of the elasmobranch electric fish. Specific antibodies generated
      against the intracellular domain of electric fish neurexin were used in
      immunocytochemical and Western blot analyses of the electromotor neurons that
      innervate the electric organ. Our results indicate that neurexin is not expressed
      at electric organ nerve terminals, as expected by the neurexin hypothesis.
      Instead, neurexin is expressed by electromotor neurons and on myelinated axons.
      This neurexin has a molecular weight of 140 kDa, consistent with an alpha
      neurexin. In addition, we find that perineurial cells of the electromotor nerve
      also express a neurexin. These cells surround bundles of axons to form a
      diffusion barrier and are thought to be a special form of fibroblast. The results
      of the study argue against a universal role for neurexins as nerve terminal
      specific proteins but suggest that neurexins are involved in axon-Schwann cell
      and perineurial cell interactions.

PMID- 9169534
TI  - Prevention of normally occurring and deafferentation-induced neuronal death in
      chick brainstem auditory neurons by periodic blockade of AMPA/kainate receptors.
AB  - The role of glutamate receptors in regulating programmed neuronal death and
      deafferentation-induced neuronal death in the brainstem auditory nuclei was
      studied by in ovo drug administration to chick embryos. The nucleus laminaris
      (NL) undergoes programmed developmental cell death of 19% between embryonic day 9
      (E9) and E17. The AMPA/kainate receptor antagonist CNQX, when administered at
      doses of 200-300 microg/d from E8 to E15, prevented programmed neuronal death in
      NL through at least posthatching day 8, without producing anatomical or
      behavioral abnormalities. 3-((RS)-2-Carboxypiperazin-4-yl)-propyl-1-phos-phonic
      acid, an antagonist of NMDA receptors, had no effect on normal cell death in the
      NL. CNQX, given from E8 to E15 or only from E8 to E10, also blocked the 33%
      neuronal loss in the nucleus magnocellularis (NM) that follows surgical
      destruction of the otocyst on E3, a procedure that deafferents NM neurons by
      preventing formation of the cochlear nerve. Treatment either with CNQX or the
      more highly selective NBQX from E8 to E10, before the onset of synaptic
      transmission in NM and NL, was also effective in preventing normal neuronal death
      in NL. Analysis of the effects of CNQX or NBQX on spontaneous embryonic motility
      at E10 showed that the doses effective in preventing neuronal death suppressed
      motility for <8 hr. We conclude that periodic blockade of AMPA/kainate receptors
      can protect CNS neurons against subsequent programmed cell death or
      deafferentation-induced death.

PMID- 9169535
TI  - Local release of GABAergic inhibition in the motor cortex induces immediate-early
      gene expression in indirect pathway neurons of the striatum.
AB  - The neocortex is thought to exert a powerful influence over the functions of the
      basal ganglia via its projection to the striatum. It is not known, however,
      whether corticostriatal effects are similar across different types of striatal
      projection neurons and interneurons or are unique for cells having different
      functions within striatal networks. To examine this question, we developed a
      method for focal synchronous activation of the primary motor cortex (MI) of
      freely moving rats by local release of GABAergic inhibition. With this method, we
      monitored cortically evoked activation of two immediate-early gene protein
      products, c-Fos and JunB, in phenotypically identified striatal neurons. We
      further studied the influence of glutamate receptor antagonists on the stimulated
      expression of c-Fos, JunB, FosB, and NGFI-A. Local disinhibition of MI elicited
      remarkably selective induction of c-Fos and JunB in enkephalinergic projection
      neurons. These indirect pathway neurons, through their projections to the globus
      pallidus, can inhibit thalamocortical motor circuits. The dynorphin-containing
      projection neurons of the direct pathway, with opposite effects on the
      thalamocortical circuits, showed very little induction of c-Fos or JunB. The gene
      response of striatal interneurons was also highly selective, affecting
      principally parvalbumin- and NADPH diaphorase-expressing interneurons. The
      glutamate NMDA receptor antagonist MK-801 strongly reduced the cortically evoked
      striatal gene expression in all cell types for each gene examined. Because the
      gene induction that we found followed known corticostriatal somatotopy, was dose
      dependent, and was selectively sensitive to glutamate receptor antagonists, we
      suggest that the differential activation patterns reflect functional
      specialization of cortical inputs to the direct and indirect pathways of the
      basal ganglia and functional plasticity within these circuits.

PMID- 9169536
TI  - Glutamatergic enteric neurons.
AB  - We tested the hypothesis that glutamate, the major excitatory neurotransmitter of
      the CNS, is also an excitatory neurotransmitter in the enteric nervous system
      (ENS). Glutamate immunoreactivity was found in cholinergic enteric neurons, many
      of which were identified as sensory by their co-storage of substance P and/or
      calbindin. Glutamate immunoreactivity was concentrated in terminal varicosities
      with a majority of small clear synaptic vesicles. The immunoreactivities of both
      AMPA and NMDA receptor subunits were also detected on neurons in both submucosal
      and myenteric plexuses. The immunoreactivity of the EAAC1 neuronal glutamate
      transporter was widespread in both plexuses. Glutamate evoked depolarizing
      responses in myenteric neurons that had fast and slow components. The fast
      component was mimicked by AMPA, and the slow component was mimicked by NMDA. The
      fast component and the response to AMPA mimicked fast EPSPs evoked in 2/AH
      neurons; moreover, fast EPSPs as well as fast glutamate and AMPA responses were
      blocked by selective AMPA antagonists and potentiated by the glutamate uptake
      inhibitor L-(-)-threo-3-hydroxyaspartic acid. These observations demonstrate, for
      the first time, the presence of glutamatergic neurons and glutamate-mediated
      neurotransmission in the ENS.

PMID- 9169537
TI  - GABA activity mediating cytosolic Ca2+ rises in developing neurons is modulated
      by cAMP-dependent signal transduction.
AB  - In the majority of developing neurons, GABA can exert depolarizing actions,
      thereby raising neuronal Ca2+. Ca2+ elevations can have broad consequences during
      development, inducing gene expression, altering neurite outgrowth and growth cone
      turning, activating enzyme pathways, and influencing neuronal survival. We used
      fura-2 and fluo-3 Ca2+ digital imaging to assess the effects of inhibiting or
      activating the cAMP signal transduction pathway on GABA activity mediating Ca2+
      rises during the early stages of in vitro hypothalamic neural development. Our
      experiments stemmed from the finding that stimulation of transmitter receptors
      shown to either activate or inhibit adenylyl cyclase activity caused a rapid
      decrease in Ca2+ rises mediated by synaptically released GABA. Both the adenylyl
      cyclase activator forskolin and the inhibitor SQ-22,536 reduced the Ca2+ rise
      elicited by the synaptic release of GABA. Bath application of the membrane
      permeable cAMP analogs 8-bromo-cAMP (8-Br-cAMP) or 8-(4-chlorophenylthio)-cAMP
      (0.2-5 mM) produced a rapid, reversible, dose-dependent inhibition of Ca2+ rises
      triggered by synaptic GABA release. Potentiation of GABAergic activity mediating
      Ca2+ rises was observed in some neurons at relatively low concentrations of the
      membrane-permeable cAMP analogs (20-50 microM). In the presence of tetrodotoxin
      (TTX), postsynaptic Ca2+ rises triggered by the bath application of GABA were
      only moderately depressed (13%) by 8-Br-cAMP (1 mM), suggesting that the
      inhibitory effects of 8-Br-cAMP were largely the result of a presynaptic
      mechanism. The protein kinase A (PKA) inhibitors H89 and Rp-3', 5'-cyclic
      monophosphothioate triethylamine also caused a large reduction (>70%) in Ca2+
      rises triggered by synaptic GABA release. Unlike the short-term depression
      elicited by activation of the cAMP signal transduction pathway, Ca2+ depression
      elicited by PKA inhibition persisted for an extended period (>30 min) after PKA
      inhibitor washout. Postsynaptic depression of GABA-evoked Ca2+ rises triggered by
      H89 (in the presence of TTX) recovered rapidly, suggesting that the extended
      depression observed during synaptic GABA release was largely through a
      presynaptic mechanism. Long-term Ca2+ modulation by cAMP-regulating hypothalamic
      peptides may be mediated through a parallel mechanism. Together, these results
      suggest that GABAergic activity mediating Ca2+ rises is dependent on ongoing PKA
      activity that is maintained within a narrow zone for GABA to elicit a maximal
      Ca2+ elevation. Thus, neuromodulator-mediated changes in the cAMP-dependent
      signal transduction pathway (activation or inhibition) could lead to a
      substantial decrease in GABA-mediated Ca2+ rises during early development.

PMID- 9169538
TI  - Regional cerebral blood flow changes as a function of delta and spindle activity
      during slow wave sleep in humans.
AB  - In the present study, we investigated changes in regional cerebral blood flow
      (rCBF) in humans during the progression from relaxed wakefulness through slow
      wave sleep (SWS). These changes were examined as a function of spindle (12-15 Hz)
      and delta (1.5-4.0 Hz) electroencephalographic (EEG) activity of SWS. rCBF was
      studied with positron emission tomography (PET) using the H215O bolus method. A
      maximum of six 60 sec scans were performed per subject during periods of
      wakefulness and stages 1-4 of SWS, as determined by on-line EEG monitoring.
      Spectral analysis was performed off-line on the EEG epochs corresponding to the
      scans for computation of activity in specific frequency bands. The relationship
      between EEG frequency band activity and normalized rCBF was determined by means
      of a voxel-by-voxel analysis of covariance. delta activity covaried negatively
      with rCBF most markedly in the thalamus and also in the brainstem reticular
      formation, cerebellum, anterior cingulate, and orbitofrontal cortex. After the
      effect of delta was removed, a significant negative covariation between spindle
      activity and the residual rCBF was evident in the medial thalamus. These negative
      covariations may reflect the disfacilitation and active inhibition of
      thalamocortical relay neurons in association with delta and spindles, as well as
      the neural substrates underlying the progressive attenuation of sensory
      awareness, motor responsiveness, and arousal that occur during SWS. delta
      activity covaried positively with rCBF in the visual and auditory cortex,
      possibly reflecting processes of dream-like mentation purported to occur during
      SWS.

PMID- 9169539
TI  - Encoding of visual motion information and reliability in spiking and graded
      potential neurons.
AB  - We investigated the information about stimulus velocity inherent in the membrane
      signals of two types of directionally selective, motion-sensitive interneurons in
      the fly visual system. One of the cells, the H1-cell, is a spiking neuron,
      whereas the other, the HS-cell, encodes sensory information mainly by a graded
      shift of its membrane potential. Using a pseudo-random velocity waveform by which
      a visual grating is moving along the horizontal axis of the eye, both cell types
      follow the stimulus velocity at higher precision than in response to a step-like
      velocity function. To measure how much information about the stimulus velocity is
      preserved in the cellular responses, we calculated the coherence between the
      stimulus and the neural signals as a function of stimulus frequency. At
      frequencies up to approximately 10 Hz motion information is well contained in the
      electrical signals of HS- and H1-cells: For HS-cells the coherence value amounts
      to approximately 70%, and for H1-cells this value is approximately 60%. Comparing
      these values with the coherence expected from a linear encoding reveals that the
      fidelity of the original stimulus is deteriorated in the neural signal partly by
      neural noise and partly by the nonlinearity inherent in the process of visual
      motion detection. The degree to which this nonlinearity contributes to the
      decrease in coherence depends on the maximum velocity used in the experiments;
      the smaller the stimulus amplitude, the higher the coherence and, thus, the
      smaller the nonlinearity in encoding of stimulus motion. All these results are in
      agreement with model simulations in which visual motion is processed by an array
      of local motion detectors, the spatially integrated output of which is considered
      the equivalent of the neural signals of HS- and H1-cells.

PMID- 9169540
TI  - Studies on long-term depression in area CA1 of the anesthetized and freely moving
      rat.
AB  - Homosynaptic long-term depression (LTD) is reported to occur in field CA1 of
      hippocampal slices collected from immature brains. Because the effect has been
      postulated to be a memory storage mechanism, it is of interest to test for its
      presence in adult, awake animals. Unfortunately, not only has hippocampal LTD
      proved difficult to obtain reliably in vivo, but the few successful studies vary
      with respect to protocols and evidence that the depression is input-specific. The
      present study tested for input-specific (homosynaptic) LTD in field CA1 after
      application of various stimulation protocols to the Schaffer
      collateral/commissural projections in freely moving, adult rats. The results
      indicate that although low-frequency trains do induce decrements in synaptic
      transmission lasting for hours to several days, the success rate of eliciting
      input-specific LTD in the awake rat is very modest compared with the ease with
      which stable potentiation is obtained in the same synapses. Moreover, it is
      questionable that the effective protocols represent patterns of activity likely
      to occur during behavior. The stronger the afferent activation during low
      frequency stimulation, the greater was the probability of eliciting LTD
      accompanied by persistent heterosynaptic depression. Clear evidence for the
      occurrence of LTD, irrespective of stimulation protocol and current intensity,
      could not be obtained in rats under barbiturate anesthesia. In all, the results
      do not accord with the suggestion that LTD occurs routinely in the hippocampus in
      vivo as part of memory encoding.

PMID- 9169541
TI  - Ventral prefrontal cortex is not essential for working memory.
AB  - It is widely held that the prefrontal cortex is important for working memory. It
      has been suggested that the inferior convexity (IC) may play a special role in
      working memory for form and color (). We have therefore assessed the ability of
      monkeys with IC lesions to perform visual pattern association tasks and color
      matching tasks, both with and without delay. In experiment 1, six monkeys were
      trained on a visual association task with delays of up to 2 sec. Conservative IC
      lesions that removed lateral area 47/12 in three animals had no effect on the
      task. Further experiments showed that these lesions had no effect on the
      postoperative new learning of a color-matching task with delays of up to 2 sec or
      versions of the visual association task involving delays of up to 8 sec. In
      experiment 2, larger lesions of both areas 47/12 and 45A were made in the three
      control animals. This lesion caused a profound deficit in the ability to relearn
      simultaneous color matching, but subsequent matching with delays of up to 8 sec
      was clearly unimpaired. We suggest that the IC may be more important for stimulus
      selection and attention as opposed to working memory.

PMID- 9169542
TI  - Dual ultrastructural localization of mu-opioid receptors and NMDA-type glutamate
      receptors in the shell of the rat nucleus accumbens.
AB  - The effectiveness of NMDA antagonists in modulating the motor and motivational
      effects of opiates is attributed, in part, to functional associations involving
      NMDA receptors and micro-opioid receptors (MORs) in the shell of the nucleus
      accumbens (Acb). To determine the subcellular sites for potential functional
      interactions between opiate ligands and NMDA receptors in this region, we
      examined the ultrastructural localization of antipeptide antisera against MOR and
      the R1 subunit of the NMDA receptor in the Acb shell of the adult rat brain. MOR
      like immunoreactivity (MOR-LI) was seen primarily in dendrites, whereas NMDAR1
      like immunoreactivity (NMDAR1-LI) was detected more often in axon terminals
      forming asymmetric synapses. In these profiles, MOR labeling was localized mainly
      to extrasynaptic plasma membranes, whereas NMDAR1-LI was associated with both
      synaptic and extrasynaptic sites. Of 307 MOR-labeled processes, 17.9% of the
      dendrites and 9.4% of the axon terminals also contained NMDAR1-LI. In addition,
      24.7% of the dendrites containing only MOR-LI were apposed to NMDAR1-labeled
      axons or terminals. We conclude that in the shell of the Acb, the output of
      single neurons can be dually modulated by (1) activation of MOR and NMDA
      receptors in the same dendrites or (2) combined activation of presynaptic NMDA
      receptors in afferents contacting dendrites containing MOR. In addition, the
      colocalization of MOR and NMDAR1 in certain axon terminals in the Acb suggests
      their dual involvement in the presynaptic release of neurotransmitters in this
      region.

PMID- 9169543
TI  - Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect
      in male rats.
AB  - The Coolidge effect describes the reinitiation of sexual behavior in a "sexually
      satiated" animal in response to a novel receptive mate. Given the role of the
      mesolimbic dopamine (DA) system in the initiation and maintenance of motivated
      behavior, microdialysis was used to monitor nucleus accumbens (NAC) DA
      transmission during copulation, sexual satiety, and the reinitiation of sexual
      behavior. In agreement with earlier reports, the presentation of an estrous
      female behind a screen and copulation were associated with significant increases
      in NAC DA efflux. Return of NAC DA concentrations to baseline values coincided
      with a period of sexual satiety, although concentrations of the DA metabolites,
      dihydroxyphenylacetic acid and homovanillic acid, remained elevated. The
      presentation of a novel receptive female behind a screen resulted in a slight
      increase in NAC DA, which was augmented significantly during renewed copulation
      with the novel female. The present data suggest that the stimulus properties of a
      novel receptive female may serve to increase NAC DA transmission in a sexually
      satiated male rat, and this, in turn, may be related to the reinitiation of
      sexual behavior.

PMID- 9169544
TI  - Fetal transplants alter the development of function after spinal cord transection
      in newborn rats.
AB  - Pieces of fetal spinal tissue were transplanted into the site of complete
      midthoracic spinal transections in neonatal rat pups (transplant rats). The
      development of locomotion in these animals was compared with that of unoperated
      control rats and rats that received spinal transections alone (spinal rats).
      Reflex, treadmill and overground locomotion, staircase descent, and horizontal
      ladder crossing for a water reward were tested in control, spinal, and transplant
      rats from 3 weeks to adulthood. All tests were readily performed by control
      animals. Most spinal rats were unable to make many linked weight-supported steps
      on these tasks. Transplant rats were variable in their locomotor capabilities,
      but a subset of rats were able to demonstrate coordinated and adaptable
      locomotion on these tasks. Some transplant rats performed better on more
      challenging tasks, suggesting that motor strategies for these tasks used
      different information, perhaps from descending systems. Transplanted tissue
      survived, and in most cases there was immunocytochemical staining of serotonergic
      fibers passing into and caudal to the transplant, supporting the conclusion that
      descending systems grew through the transplanted tissue. Integration with the
      host tissue was often poor, suggesting that nonspecific or trophic effects of the
      transplant might also contribute to the development of locomotor function.
      Therefore several mechanisms may contribute to the repair of injured spinal cord
      provided by transplants that permit the development of useful locomotion.

PMID- 9169545
TI  - Parallel medullary gustatospinal pathways in a catfish: possible neural
      substrates for taste-mediated food search.
AB  - Taste and tactile fibers in the facial nerve of catfish innervate extraoral taste
      buds and terminate somatotopically in the facial lobe (FL)-a medullary structure
      crucial for gustatory-mediated food search. The present study was performed to
      determine the neural linkages between the gustatory input and the spinal motor
      output. Spinal injections of horseradish peroxidase (HRP) label spinopetal cells
      in the octaval nuclei, the nucleus of the medial longitudinal fasciculus, and
      reticulospinal neurons (Rsps) in the brainstem medial reticular formation (RF),
      including the Mauthner cell. A somatotopically organized, direct faciospinal
      system originating from superficial cells scattered in the lateral lobule of the
      facial lobe (ll) is also labeled. The brainstem reticulospinal cells are
      segmentally organized into 14 clusters within eight segments of the reticular
      formation and includes one cluster (RS5) directly ventral to the FL. Injections
      of HRP or fluorescent tracers into the medial lobule of the FL label a
      facioreticular projection terminating around the Rsps of RS5. DiI injections into
      this area of the RF retrogradely label deeply situated bipolar neurons,
      especially in the medial and intermediate lobules of the FL. Electrophysiological
      recordings in and around RS5 show units with large receptive fields and with
      responses to chemical and tactile stimulation. The FL projects to the spinal cord
      via two pathways: (1) a topographically organized direct faciospinal pathway, and
      (2) an indirect facioreticulospinal pathway in which reticular neurons process
      and integrate gustatory information before influencing spinal circuitry for motor
      control during food search.

PMID- 9169546
TI  - Inhibition of stress-induced neuroendocrine and behavioral responses in the rat
      by prepro-thyrotropin-releasing hormone 178-199.
AB  - A corticotropin release-inhibiting factor (CRIF) in brain has been postulated for
      several decades, based on increased plasma levels of ACTH and corticosterone
      after hypothalamic-pituitary disconnection. Recent in vitro studies indicate that
      prepro-TRH178-199 may function as an endogenous CRIF, prompting us to examine
      stress-related neuroendocrine and behavioral responses after in vivo
      administration to the adult male rat. Animals that were administered prepro
      TRH178-199 intravenously 5 min before restraint stress exhibited a significant
      attenuation of stress-induced elevations of ACTH, corticosterone, and prolactin,
      as compared with controls infused with vehicle, whereas thyroid-stimulating
      hormone (TSH) secretion was not changed. In behavioral studies of stress
      responsiveness, either the vehicle or prepro-TRH178-199 was administered
      intracerebroventricularly (ICV) 5 min before testing. In the open field, prepro
      TRH178-199 significantly increased grooming, locomotor activity, rearing, and
      sniffing behaviors. In the light/dark box, it significantly increased the time
      animals spent in the light compartment and increased the number of crossings
      between the light/dark compartments. In the plus maze, the peptide significantly
      increased the amount of time animals spent in the open arms. The same dose of
      peptide, administered ICV, had no effect on peripheral hormone release in
      response to restraint stress. Overall, these results support a role for prepro
      TRH178-199 in the inhibition of the neuroendocrine responses to stress at the
      level of the pituitary and indicate that it has central modulatory influences
      over stress-related behaviors.

PMID- 9169547
TI  - Chronic social stress alters levels of corticotropin-releasing factor and
      arginine vasopressin mRNA in rat brain.
AB  - In the visible burrow system model of chronic social stress, male rats housed in
      mixed-sex groups quickly form a dominance hierarchy in which the subordinates
      appear to be severely stressed. A subgroup of subordinates have an impaired
      corticosterone response after presentation of a novel restraint stressor, leading
      to their designation as nonresponsive subordinates. To examine the mechanism
      underlying the blunted corticosterone response in these animals, in situ
      hybridization histochemistry was used to quantify corticotropin-releasing factor
      (CRF) and arginine vasopressin (AVP) mRNA expression in the brain. In two
      separate visible burrow system experiments, the nonresponsive subordinates
      expressed a significantly lower average number of CRF mRNA grains per cell in the
      paraventricular hypothalamic nucleus compared with stress-responsive
      subordinates, dominants (DOM), or cage-housed control (CON) rats. The number of
      CRF mRNA labeled cells was also significantly lower in nonresponders than in
      responsive subordinates or DOM. In the central amygdala, CRF mRNA levels were
      increased in both groups of subordinates compared with CON rats, whereas
      responsive subordinates exhibited higher levels than the DOM rats as well. AVP
      mRNA levels did not vary with behavioral rank in any subdivision of the
      paraventricular hypothalamic nucleus. In the medial amygdala, the number of cells
      expressing AVP mRNA was significantly greater in CON rats compared with both
      groups of subordinates, although the average number of AVP mRNA grains per cell
      did not vary with rank. In addition, the number of AVP-positive cells
      significantly correlated with plasma testosterone level.

PMID- 9169548
TI  - Time course of cortical activations in implicit and explicit recall.
AB  - The distinction between implicit and explicit retrieval of learned material is
      central to recent thinking about the neural systems underlying memory. Word stem
      completion is one task in which subjects can be instructed either to make a
      deliberate recall (explicit instruction) or to be told to complete the stem with
      any appropriate word (implicit instruction). Positron emission tomography (PET)
      studies have indicated that during implicit retrieval, there is reduced blood
      flow in right posterior areas, whereas some tasks of explicit retrieval involve
      frontal and hippocampal activation. However, there is no information about the
      timing of these activations or how implicit and explicit retrieval might be
      related. We used word stem completion tasks similar to those used in the PET
      studies, but used high-density electrical recording designed to allow
      localization of the regions involved in the tasks and to provide temporal
      information. We found reduced activity for primed words in right posterior cortex
      corresponding to previous PET results. The reduction occurred within the first
      200 msec after input, suggesting early interaction with the information stored in
      this area. Similar reductions observed during explicit recall of the previously
      presented words indicate that priming is similar under implicit and explicit
      conditions. In addition, when priming was not an adequate basis for response,
      then frontal areas were active. Retrieval of unprimed words under implicit
      instruction elicited right frontal activation, whereas explicit retrieval
      activated frontal areas bilaterally. Left frontal and hippocampal activations
      appear to occur only when the retrieval involved use of the words from the list
      studied previously.

PMID- 9169549
TI  - Intron distribution in ancient paralogs supports random insertion and not random
      loss.
AB  - The intron positions of ten different protein families were examined to determine
      (the statistical likelihood of) whether spliceosomal introns are the result of
      random insertion events into previously intronless genes, on the one hand, or the
      result of random loss from common ancestral introns, on the other. The number of
      expected matches for the alternative scenarios was calculated for a binomial
      distribution by considering currently observed introns relative to all possible
      locations for insertion or loss. Introns occurring at approximately the same
      location (hereafter called a "match") were tallied for each of the paired
      proteins. Matches were identified by their positions in the multiple alignment
      and were defined as any two introns occurring within a window of 11 possible
      nucleotide positions, thereby allowing for possible alignment errors and "intron
      sliding." Matches were tallied from the raw data and compared with the expected
      number of matches for the two different scenarios. The results suggest that the
      distribution of introns in genes encoding proteins is due to random insertion and
      not random loss.

PMID- 9169550
TI  - engrailed duplication events during the evolution of barnacles.
AB  - Barnacles (Cirripedia) are a subclass of Crustacea. Their peculiar segmentation
      pattern (few segments, absence of abdominal segments, and, in the parasitic
      rhizocephalan, loss of segmentation at the adult stage) prompted us to study the
      engrailed gene, which encodes a homeodomain transcription factor and is expressed
      in arthropods in the posterior half of each segment. We searched for engrailed
      genes by PCR in a representative cross section of the Cirripedia. Eight
      unambiguous engrailed genes were cloned from five species, three genes belonging
      to the same species (Elminius modestus). This implies two duplication events.
      Molecular phylogenies were constructed and a cladistic approach was applied to
      the most informative sites. The results indicate that the older duplication
      (en.a/en.b) is probably very ancient and concerns the whole cirripedean subclass,
      whereas the other (en.a1/en.a2) is specific to the Elminius lineage.

PMID- 9169551
TI  - Thyroid hormone receptor genes of neotenic amphibians.
AB  - Since thyroid hormones play a pivotal role in amphibian metamorphosis we used PCR
      to amplify DNA fragments corresponding to a portion of the ligand-binding domain
      of the thyroid hormone receptor (TR) genes in several neotenic amphibians: the
      obligatory neotenic members of the family Proteidea the mudpuppy Necturus
      maculosus and Proteus anguinus as well as two members of the facultative neotenic
      Ambystoma genus: the axolotl Ambystoma mexicanum and the tiger salamander
      Ambystoma tigrinum. In addition, we looked for TR genes in the genome of an apode
      Typhlonectes compressicaudus. TR genes were found in all these species including
      the obligatory neotenic ones. The PCR fragments obtained encompass both the C and
      E domains and correspond to alpha and beta genes. Their sequences appear to be
      normal, suggesting that there is no acceleration of evolutionary rates in the TR
      genes of neotenic amphibians. This result is not surprising for Ambystomatidae,
      which are known to respond to T3 (3,3',5-triiodothyronine) but is not in
      agreement with biochemical and biological data showing that Proteidea cannot
      respond to thyroid hormones. Interestingly, by RT-PCR analysis we observed a high
      expression levels of TRalpha in gills, intestine, and muscles of Necturus as well
      as in the liver of Ambystoma mexicanum, whereas TRbeta expression was only
      detected in Ambystoma mexicanum but not in Necturus. Such a differential
      expression pattern of TRalpha and TRbeta may explain the neoteny in Proteidea.
      The cloning of thyroid-hormone-receptor gene fragments from these species will
      allow the molecular study of their failure to undergo metamorphosis.

PMID- 9169552
TI  - Nonplastid eukaryotic response regulators have a monophyletic origin and evolved
      from their bacterial precursors in parallel with their cognate sensor kinases.
AB  - We have analyzed all currently sequenced eukaryotic proteins containing either a
      kinase module or a receiver module, corresponding to those found in bacterial
      sensor kinases or response regulators, respectively, of the so-called two
      component regulatory systems. We demonstrate that the eukaryotic receiver modules
      belong to a single subfamily of the bacterial receiver modules. Moreover, the
      cognate eukaryotic kinase modules exhibit a similar clustering pattern on the
      sensor kinase phylogenetic tree, suggesting that they evolved in parallel with
      the receiver modules from a common ancestral source that bore both modules.
      Multiple alignments of the sequences corresponding to these modules are presented
      and discussed, and eukaryotic-specific signature sequences are derived.

PMID- 9169554
TI  - On the informational content of overlapping genes in prokaryotic and eukaryotic
      viruses.
AB  - In genetic language a peculiar arrangement of biological information is provided
      by overlapping genes in which the same region of DNA can code for functionally
      unrelated messages. In this work, the informational content of overlapping genes
      belonging to prokaryotic and eukaryotic viruses was analyzed. Using information
      theory indices, we identified in the regions of overlap a first pattern,
      exhibiting a more uniform base composition and more severe constraints in base
      ordering with respect to the nonoverlapping regions. This pattern was found to be
      peculiar to coliphage, avian hepatitis B virus, human lentivirus, and plant
      luteovirus families. A second pattern, characterized by the occurrence of similar
      compositional constraints in both types of coding regions, was found to be
      limited to plant tymoviruses. At the level of codon usage, a low degree of
      correlation between overlapping and nonoverlapping coding regions characterized
      the first pattern, whereas a close link was found in tymoviruses, indicating a
      fine adaptation of the overlapping frame to the original codon choice of the
      virus. As a result of codon usage correlation analysis, deductions concerning the
      origin and evolution of several overlapping frames were also proposed. Comparison
      of amino acid composition revealed an increased frequency of amino acid residues
      with a high level of degeneracy (arginine, leucine, and serine) in the proteins
      encoded by overlapping genes; this peculiar feature of overlapping genes can be
      viewed as a way with which they may expand their coding ability and gain new,
      specialized functions.

PMID- 9169555
TI  - Relationships between genomic G+C content, RNA secondary structures, and optimal
      growth temperature in prokaryotes.
AB  - G:C pairs are more stable than A:T pairs because they have an additional hydrogen
      bond. This has led to many studies on the correlation between the
      guanine+cytosine (G+C) content of nucleic acids and temperature over the last 20
      years. We collected the optimal growth temperatures (Topt) and the G+C contents
      of genomic DNA; 23S, 16S, and 5S ribosomal RNAs; and transfer RNAs for 764
      prokaryotic species. No correlation was found between genomic G+C content and
      Topt, but there were striking correlations between the G+C content of ribosomal
      and transfer RNA stems and Topt. Two explanations have been proposed-neutral
      evolution and selection pressure-for the approximate equalities of G and C
      (respectively, A and T) contents within each strand of DNA molecules. Our results
      do not support the notion that selection pressure induces complementary
      oligonucleotides in close proximity and therefore numerous secondary structures
      in prokaryotic DNA, as the genomic G+C content does not behave in the same way as
      that of folded RNA with respect to optimal growth temperature.

PMID- 9169553
TI  - Structural and evolutionary relationships among chitinases of flowering plants.
AB  - The analysis of nuclear-encoded chitinase sequences from various angiosperms has
      allowed the categorization of the chitinases into discrete classes. Nucleotide
      sequences of their catalytic domains were compared in this study to investigate
      the evolutionary relationships between chitinase classes. The functionally
      distinct class III chitinases appear to be more closely related to fungal enzymes
      involved in morphogenesis than to other plant chitinases. The ordering of other
      plant chitinases into additional classes mainly relied on the presence of
      auxiliary domains-namely, a chitin-binding domain and a carboxy-terminal
      extension-flanking the main catalytic domain. The results of our phylogenetic
      analyses showed that classes I and IV form discrete and well-supported
      monophyletic groups derived from a common ancestral sequence that predates the
      divergence of dicots and monocots. In contrast, other sequences included in
      classes I* and II, lacking one or both types of auxiliary domains, were nested
      within class I sequences, indicating that they have a polyphyletic origin.
      According to phylogenetic analyses and the calculation of evolutionary rates,
      these chitinases probably arose from different class I lineages by relatively
      recent deletion events. The occurrence of such evolutionary trends in cultivated
      plants and their potential involvement in host-pathogen interactions are
      discussed.

PMID- 9169556
TI  - Origin and inheritance of group I introns in 26S rRNA genes of Gaeumannomyces
      graminis.
AB  - Studies of the distribution of the three group I introns (intron A, intron T, and
      intron AT) in the 26S rDNA of Gaeumannomyces graminis had suggested that they
      were transferred to a common ancestor of G. graminis var. avenae and var. tritici
      after it had branched off from var. graminis. Intron AT and intron A exhibited
      vertical inheritance and coevolved in concert with their hosts. Intron loss could
      occur after its acquisition. Loss of any one of the three introns could occur in
      var. tritici whereas only loss of intron T had been found in the majority of var.
      avenae isolates. The existence of isolates of var. tritici and var. avenae with
      three introns suggested that intron loss could be reversed by intron acquisition
      and that the whole process is a dynamic one. This process of intron acquisition
      and intron loss reached different equilibrium points for different varieties and
      subgroups, which explained the irregular distribution of these introns in G.
      graminis. Each of the three group I introns was more closely related to other
      intron sequences that share the same insertion point in the 26S rDNA than to each
      other. These introns in distantly related organisms appeared to have a common
      ancestry. This system had provided a good model for studies on both the lateral
      transfer and common ancestry of group I introns in the 26S rRNA genes.

PMID- 9169557
TI  - Segmented gene conversion as a mechanism of correction of 18S rRNA pseudogene
      located outside of rDNA cluster in D. melanogaster.
AB  - The peculiarities of the sequences of 18S rDNA included in a 90-kb DNA segment
      cloned in YAC vector are described. This heterochromatic segment is situated on
      the X chromosome distal to the main rDNA cluster. The pseudo 18S rDNA sequence
      comprised undamaged stretches of rDNA interspersed with segments characterized by
      high density of nucleotide substitutions and insertions/deletions. The observed
      patchwork arrangement of unaltered rDNA sequences was considered as evidence of
      segmented gene conversion events between the normal and damaged genes which are
      thought to constitute one of the mechanisms of rDNA array homogenization. The 18S
      rDNA fragment (510 bp) located nearby, homologous to the internal, undamaged part
      of pseudo 18S rDNA, carries comparable density of randomly distributed nucleotide
      substitutions with no evidence of correction.

PMID- 9169558
TI  - Characterization of a small family (CAIII) of microsatellite-containing sequences
      with X-Y homology.
AB  - Four X-linked loci showing homology with a previously described Y-linked
      polymorphic locus (DYS413) were identified and characterized. By fluorescent in
      situ hybridization (FISH), somatic cell hybrids, and YAC screening, the X-linked
      members of this small family of sequences (CAIII) all map in Xp22, while the Y
      members map in Yq11. These loci contribute to the overall similarity of the two
      genomic regions. All of the CAIII loci contain an internal microsatellite of the
      (CA)n type. The microsatellites display extensive length polymorphism in two of
      the X-linked members as well as in the Y members. In addition, common sequence
      variants are found in the portions flanking the microsatellites in two of the X
      linked members. Our results indicate that, during the evolution of this family,
      length variation on the Y chromosome was accumulated at a rate not slower than
      that on the X chromosome. Finally, these sequences represent a model system with
      which to analyze human populations for similar X- and Y-linked polymorphisms.

PMID- 9169559
TI  - Evolutionary shifts in three major structural features of the mitochondrial
      genome among iguanian lizards.
AB  - A phylogenetic tree for major lineages of iguanian lizards is estimated from
      1,488 aligned base positions (858 informative) of newly reported mitochondrial
      DNA sequences representing coding regions for eight tRNAs, ND2, and portions of
      ND1 and COI. Two well-supported groups are defined, the Acrodonta and the
      Iguanidae (sensu lato). This phylogenetic hypothesis is used to investigate
      evolutionary shifts in mitochondrial gene order, origin for light-strand
      replication, and secondary structure of tRNACys. These three characters shift
      together on the branch leading to acrodont lizards. Plate tectonics and the
      fossil record indicate that these characters changed in the Jurassic. We propose
      that changes to the secondary structure of tRNACys may destroy function of the
      origin for light-strand replication which, in turn, may facilitate shifts in gene
      order.

PMID- 9169561
TI  - A conserved motif at the carboxy terminus of MAP kinases.

PMID- 9169560
TI  - Coordinated amino acid changes in the evolution of mammalian defensins.
AB  - The mammalian defensin molecule is a short, highly cationic peptide cytotoxic to
      both microbial and mammalian cells which is cleaved from a precursor including a
      signal peptide and a highly anionic propiece. A phylogenetic analysis of 28
      complete sequences from five mammalian species (mouse, rat, guinea pig, rabbit,
      and human) showed species-specific clusters of sequences, indicating that the
      genes duplicated after divergence of these species. Comparison of rates of
      synonymous and nonsynonymous nucleotide substitution suggested that gene
      duplication has often been followed by a period in which diversification of the
      mature defensins at the amino acid level has been selectively favored. In some
      comparisons, it appeared that amino acid differences in this region have appeared
      in a nonrandom fashion so as to change the pattern of residue charges. Because it
      has been hypothesized that the negative charge in the propiece serves to balance
      the positive charge in the mature defensin and thus to prevent cytotoxicity prior
      to cleavage, we used a maximum likelihood method of reconstructing ancestral
      states in order to test whether this balance has been maintained over
      evolutionary time in spite of rapid diversification of the mature defensin at the
      amino acid level. Reconstructed ancestral sequences always maintained a charge
      balance between mature defensin and propiece, and changes in the net positive
      charge of the mature defensin were balanced by corresponding changes in the
      propiece. The results support the hypothesis that, in the evolution of these
      proteins, amino acid changes have occurred in a coordinated fashion so as to
      preserve an adaptive phenotype.

PMID- 9169562
TI  - Unidentified open reading frames in the genome of Methanococcus jannaschii are
      similar in sequence to an archaebacterial gene for tRNA nucleotidyltransferase.
AB  - The protein sequence of ATP/CTP:tRNA nucleotidyltransferase (cca) from Sulfolobus
      shibatae was used to search open reading frames in the genome of Methanococcus
      jannaschii. Translations of two unidentified open reading frames showed
      significant sequence similarity to portions of the Sulfolobus cca protein. When
      the two open reading frames were joined together, the expanded open reading frame
      was similar in sequence to the entire Sulfolobus cca protein and displayed
      features of the active site signature sequence proposed for members of class I
      enzymes within the superfamily of nucleotidyltransferases (Yue et al., 1996, RNA
      2, 895-908). A possible UUG start codon was identified based on significant
      sequence similarity of the resulting amino-terminal region to that of Sulfolobus,
      and on a six-base complementarity between an adjacent upstream sequence and
      Methanococcus 16S rRNA.

PMID- 9169563
TI  - Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced
      radiotherapeutic drug of potential value for the treatment of bone metastases.
AB  - The search for an ideal radioisotope for systemic radiotherapy continues. As a
      generator-produced radioisotope emitting both beta and gamma rays and having a
      short physical half-life of 16.9 h, rhenium-188 is a very good potential
      candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene
      diphosphonate (HEDP) with 188Re and analyzed the biodistribution and bone uptake
      following intravenous injection in rats to assess its potential for clinical use.
      The rats were injected with approximately 14.8 MBq (0.4 mCi) 188Re-HEDP in a
      volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four
      rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis,
      muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In
      addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was
      taken from the urinary bladder immediately after killing. Tissue concentrations
      were calculated and expressed as percent injected dose per gram or per milliliter
      (% ID/g or ml). Bone lesions were created in the right tibial bone in three
      rabbits to calculate the lesion to normal uptake ratio (L/N ratio). The
      biodistribution data showed that the radioactivity in the bone tissue was as high
      as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity
      level in the kidney was highest at 1 h but declined rapidly throughout the study.
      The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool
      were all lower than 0.3% ID/g at 1 h and also declined rapidly. The biological
      half-life in bone was the longest (60.86 h). In contrast, the biological half
      lives in muscle and blood were short (2.99 h and 6.21 h respectively). The
      concentrations of radioactivity in muscle, spleen, testis, and stool were quite
      low throughout the study. Most of the radiotracer was excreted by the urinary
      system. The L/N ratio was 4.23+/-0.21 in rabbits injected with 188Re-HEDP and
      4.25+/-0.23 in those injected with technetium-99m methylene diphosphonate. In
      conclusion, we would suggest that 188Re-HEDP is a very good potential candidate
      for the treatment of bone metastases because of the following characteristics:
      (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma
      rays suitable for imaging; (4) there is highly selective uptake in the skeletal
      system and bone lesions; and (5) it has a low non-target uptake and rapid
      clearance in nonosseous tissue.

PMID- 9169564
TI  - In vitro and in vivo characterisation of nor-beta-CIT: a potential radioligand
      for visualisation of the serotonin transporter in the brain.
AB  - Radiolabelled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT) has been
      used in clinical studies for the imaging of dopamine and serotonin transporters
      with single-photon emission tomography (SPET). 2beta-Carbomethoxy-3beta-(4
      iodophenyl)nortropane (nor-beta-CIT) is a des-methyl analogue of beta-CIT, which
      in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter
      than beta-CIT (IC50=4.2 nM). Nor-beta-CIT may thus be a useful radioligand for
      imaging of the serotonin transporter. In the present study iodine-125 and carbon
      11 labelled nor-beta-CIT were prepared for in vitro autoradiographic studies on
      post-mortem human brain cryosections and for in vivo positron emission tomography
      (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with
      [125I]nor-beta-CIT demonstrated high binding in the striatum, the thalamus and
      cortical regions of the human brain. Addition of a high concentration (1 microM)
      of citalopram inhibited binding in the thalamus and the neocortex, but not in the
      striatum. In PET studies with [11C]nor-beta-CIT there was rapid uptake of
      radioactivity in the monkey brain (6% of injected dose at 15 min) and high
      accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus
      to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min,
      respectively. The ratios obtained with [11C]nor-beta-CIT were 20%-40% higher than
      those previously obtained with [11C]beta-CIT. Radioactivity in the thalamus and
      the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg).
      In conclusion, nor-beta-CIT binds to the serotonin transporter in the primate
      brain in vitro and in vivo and has potential for PET and SPET imaging of the
      serotonin transporter in human brain.

PMID- 9169565
TI  - Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's
      disease using iodine-123 dexetimide single-photon emission tomography.
AB  - Decreased muscarinic receptor binding has been suggested in single-photon
      emission tomography (SPET) studies of Alzheimer's disease. However, it remains
      unclear whether these changes are present in mildly demented patients, and the
      role of cortical atrophy in receptor binding assessment has not been
      investigated. We studied muscarinic receptor binding normalized to neostriatum
      with SPET using [123I]4-iododexetimide in five mildly affected patients with
      probable Alzheimer's disease and in five age-matched control subjects. Region of
      interest (ROI) analysis was performed in a consensus procedure blind to clinical
      diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was
      assessed by calculating percentages of cerebrospinal fluid in each ROI. An
      observer study with three observers was conducted to validate this method.
      Alzheimer patients showed statistically significantly less [123I]4-iododexetimide
      binding in left temporal and right temporo-parietal cortex compared with
      controls, independent of age, sex and cortical atrophy. Mean intra-observer
      variability was 3.6% and inter-observer results showed consistent differences in
      [123I]4-iododexetimide binding between observers. However, differences between
      patients and controls were comparable among observers and statistically
      significant in the same regions as in the consensus procedure. Using an MRI-SPET
      matching technique, we conclude that [123I]4-iododexetimide binding is reduced in
      patients with mild probable Alzheimer's disease in areas of temporal and temporo
      parietal cortex.

PMID- 9169566
TI  - Dementia with lewy bodies: a study of post-synaptic dopaminergic receptors with
      iodine-123 iodobenzamide single-photon emission tomography.
AB  - Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty
      by neuropathological examination. Diagnosis during life remains at best probable,
      based on the presence of symptoms known from autopsy studies to be frequently
      associated with DLB. The greatest practical clinical problem lies in
      distinguishing DLB and Alzheimer's disease (AD). In DLB there is a considerable
      degeneration of nigral neurones with depletion of striatal dopamine. In contrast,
      AD is not associated with significant changes in dopamine metabolism. Iodine-123
      iodobenzamide single-photon emission tomography (IBZM-SPET) measures post
      synaptic dopamine D2 neuroreceptor availability in the corpus striatum, but is
      nevertheless a method for assessing the integrity of the nigrostriatal
      dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal
      controls and 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5-2
      h after intravenous injection of 185 MBq of 123I-IBZM. Circular regions of
      interest were employed to calculate radioactivity ratios in each hemisphere as
      follows: caudate nucleus/frontal cortex, putamen/frontal cortex and caudate
      nucleus/putamen. The DLB patients had significantly lower left caudate/putamen
      ratios (95% confidence intervals: DLB 0.893-0.965, AD 0.972-1.175, controls 1.031
      1.168) than either controls or AD patients, and significantly lower right
      caudate/putamen ratios (95% confidence intervals: DLB 0.926-1.019, AD 0.954
      1.103, controls 1. 027-1.144) than controls. Our data suggest that patients with
      DLB diagnosed by clinical criteria have changes in striatal post-synaptic D2
      receptors. This may be of value in distinguishing DLB from AD during life.

PMID- 9169567
TI  - Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission
      tomography in patients with bladder cancer.
AB  - The purpose of this study was to assess the feasibility of imaging of bladder
      cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET)
      scanning. We studied 12 patients with histologically proven bladder cancer who
      had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of
      the urinary bladder with 1000-3710 ml saline was performed during nine of the
      studies. Dynamic and static PET images were obtained, and standardized uptake
      value images were reconstructed. FDG-PET scanning was true-positive in eight
      patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor
      mass lesions confirmed pathologically or clinically, 16 (80%) were detected by
      FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions
      and two of three proven regional lymph node metastases. FDG-PET was also capable
      of differentiating viable recurrent bladder cancer from radiation-induced
      alterations in two patients. In conclusion, these preliminary data indicate the
      feasibility of FDG-PET imaging in patients with bladder cancer, although a major
      remaining pitfall is intense FDG accumulation in the urine.

PMID- 9169568
TI  - A comparative study of technetium-99m sestamibi and technetium-99m tetrofosmin
      single-photon tomography in the detection of nasopharyngeal carcinoma.
AB  - The intention of this prospective study was to compare the diagnostic potential
      of technetium-99m sestamibi (MIBI) and a novel radiotracer, 99mTc-Tetrofosmin
      (Tetro), for the assessment of primary nasopharyngeal carcinoma (NPC) and the
      differentiation of residual disease from post-therapy changes. A total of 38
      patients underwent MIBI and Tetro single-photon emission tomography (SPET)
      imaging at initial presentation (n=22) or following therapy (n=16). The findings
      were correlated with computed tomography or magnetic resonance imaging (MRI) on a
      site-by-site basis. Tumour/background (Tm/Bkg) ratios were obtained on coronal
      sections. Biopsy (nine patients) and/or 12- to 24-month clinical follow-up data
      were available in the post-therapy group. All primary disease sites were
      accurately detected by both imaging studies. Although there was no statistical
      difference between the two imaging techniques in the detection of primary
      disease, MIBI was superior to Tetro in the detection of regional lymph node
      metastases (sensitivity: 95% vs 79%). Tetro and MIBI SPET were true-positive in
      all patients (n=7) with proven residual/recurrent disease. In nine patients who
      had no evidence of residual/recurrent tumour, MRI was false-positive in five
      while Tetro and MIBI SPET were false-positive in two and three patients,
      respectively. Tm/Bkg ratios were </=1.7 in all false-positive cases except one.
      Tetro, MIBI and MRI had specificities of 78%, 67% and 44%, and accuracies of
      87.5%, 81% and 69%, respectively. The results of Tetro and of MIBI SPET were not
      statistically different from one another with regard to the prediction of
      residual/recurrent or metastatic NPC.

PMID- 9169569
TI  - Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy:
      assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic
      acid myocardial single-photon emission tomography.
AB  - It has been reported that myocardial mitochondrial function can be improved by
      the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p
      iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic
      imaging using single-photon emission tomography (SPET). This study was conducted
      to determine whether the therapeutic effects of CoQ10 on idiopathic dilated
      cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients,
      comprising 14 men and one woman (mean age: 64+/-12 years), were examined. CoQ10
      was administered at 30 mg/day for a period of 35.7+/-12.4 days. BMIPP myocardial
      SPET was carried out before and after CoQ10 treatment. The count ratio of the
      heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region
      of interest method with anterior planar imaging. Representative short-axis
      tomograms were divided into 27 segments (three slicesxnine segments). Each
      segmental score was analysed semiquantitatively using a four-point scoring system
      (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio
      showed a significant improvement, from 2.39+/-0.39 to 2.54+/-0.47, after
      treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was
      significantly decreased to 10.1+/-4.3, compared to 13. 9+/-4.5 without CoQ10
      treatment (P<0.001). However, the percent fractional shortening measured using
      echocardiography was not significantly different before and after CoQ treatment
      (19.2+/-8.1 vs 19.7+/-7.1). BMIPP myocardial SPET was confirmed to be sensitive
      in evaluating the therapeutic effects of CoQ10 in patients with idiopathic
      dilated cardiomyopathy. This method is unique, since the therapeutic effects can
      be estimated from the perspective of metabolic SPET imaging.

PMID- 9169570
TI  - Scintigraphic evaluation of hepatic blood flow after intrahepatic portosystemic
      shunt (TIPS).
AB  - In patients with liver cirrhosis a transjugularly placed intrahepatic portocaval
      shunt (TIPS) is a non-surgical portosystemic device which aims to reduce portal
      venous pressure. In comparison with Doppler sonography, we evaluated in 28
      patients the diagnostic impact of liver perfusion scintigraphy (with technetium
      99m diethylene triamine penta-acetic acid) in the assessment of changes in the
      hepatic blood flow after TIPS shunting. The arterial and portal contributions to
      hepatic flow were calculated from the areas under the biphasic time-activity
      curve. In the course of TIPS shunting, patency is threatened by reocclusion.
      Angiography is the gold standard for TIPS shunt reassessment. However, there is a
      need for a less invasive diagnostic procedure, such as scintigraphy or Doppler
      sonography, for the early detection of shunt insufficiency. Scintigraphy
      demonstrated that prior to TIPS shunting the portal venous contribution to
      hepatic perfusion was reduced to 29.2%, this reduction being due to portal
      hypertension. After TIPS placement a significant increase in portal venous
      perfusion was observed (38.2%; P<0.02). TIPS shunt occlusion was identified in
      patients by a significant reduction in the scintigraphically measured portal
      venous contribution to hepatic blood flow. Hepatic perfusion scintigraphy appears
      to be a valuable method to determine the immediate effect of TIPS on hepatic
      blood flow. Post-TIPS follow-up studies of hepatic haemodynamics by liver
      perfusion scintigraphy appear able to contribute to the detection of TIPS shunt
      occlusion before the clinical consequences of this complication have become
      apparent.

PMID- 9169571
TI  - Evaluation of the limits of visual detection of image misregistration in a brain
      fluorine-18 fluorodeoxyglucose PET-MRI study.
AB  - In routine clinical work, registration accuracy is assessed by visual inspection.
      However, the accuracy of visual assessment of registration has not been
      evaluated. This study establishes the limits of visual detection of
      misregistration in a registered brain fluorine-18 fluorodeoxyglucose positron
      emission tomography to magnetic resonance image volume. The "best" registered
      image volume was obtained by automatic registration using mutual information
      optimization. Translational movements by 1 mm, 2 mm, 3 mm and 4 mm, and
      rotational movements by 1 degrees , 2 degrees , 3 degrees and 4 degrees in the
      positive and negative directions in the x- (lateral), y- (anterior-posterior) and
      z- (axial) axes were introduced to this standard. These 48 images plus six "best"
      registered images were presented in random sequence to five observers for visual
      categorization of registration accuracy. No observer detected a definite
      misregistration in the "best" registered image. Evaluation for inter-observer
      variation using observer pairings showed a high percentage of agreement in
      assigned categories for both translational and rotational misregistrations.
      Assessment of the limits of detection of misregistration showed that a 2-mm
      translational misregistration was detectable by all observers in the x- and y
      axes and 3-mm translational misregistration in the z-axis. With rotational
      misregistrations, rotation around the z-axis was detectable by all at 2 degrees
      rotation whereas rotation around the y-axis was detected at 3-4 degrees .
      Rotation around the x-axis was not symmetric with a positive rotation being
      identified at 2 degrees whereas negative rotation was detected by all only at 4
      degrees. Therefore, visual analysis appears to be a sensitive and practical means
      to assess image misregistration accuracy. The awareness of the limits of visual
      detection of misregistration will lead to increase care when evaluating
      registration quality in both research and clinical settings.

PMID- 9169572
TI  - Site-specific conjugation and labelling of prostate antibody 7E11C5.3 (CYT-351)
      with technetium-99m.
AB  - Attachment of chelating agents to the sugar residues of antibodies for subsequent
      radiolabelling is an attractive approach since it may have less effect on the
      immunoreactivity than attachment through lysine residues, which are distributed
      throughout the antibody and may be present near the antigen binding site. We have
      attached a new hydrazide-linked chelator CYT-395 (Cytogen Corp., Princeton, N.J.)
      to the sugar residues of the anti-prostate monoclonal antibody 7E11C5.3 and
      optimised the conditions for labelling the conjugate with technetium-99m in order
      to compare the conjugate to 7E11C5.3 antibody labelled directly with technetium
      using a mercaptoethanol reduction technique. Labelling yields of 70%-90% were
      obtained at specific activities up to 2000 MBq/mg antibody. The stability of the
      technetium-labelled conjugate in plasma or to a challenge with 0.1 or 1.0 mM
      cysteine was similar to that of direct-labelled antibody. In nine patients with
      prostate cancer, the plasma clearance of the labelled conjugate followed a two
      compartment model, with an average beta-phase half-life of 31.4+/-3.9 h. The
      average urinary clearance at 24 h was 15.3+/-5.0% of the injected dose. In this
      group of patients there was no significant difference between the blood and urine
      clearance of the labelled conjugate, and the clearances of the direct-labelled
      antibody.

PMID- 9169573
TI  - Rapid preparation method for technetium-99m bicisate.
AB  - The method currently recommended for the preparation of technetium-99m bicisate
      (99mTc-bicisate) requires a lengthy 30-min incubation at room temperature. The
      purpose of this study was to evaluate an alternative method to shorten the
      preparation time. 99mTc-bicisate was prepared with 3.7 GBq (100 mCi) 99mTc
      according to the manufacturer's instructions, except for the final incubation
      step, which was replaced with the microwave heating procedure. A standard thin
      layer chromatography (TLC) method (i.e., Baker-Flex silica gel IB-F TLC plate
      with ethyl acetate as mobile phase) was used for the determination of the
      radiochemical purity (RCP) of 99mTc-bicisate. Our evaluation with different
      microwave heating processes (300 W with different heating times) demonstrated
      that as the microwave heating temperature was increased (i.e., 44 masculine-71
      masculine C), an increased percentage of samples reached 95% within 5 min post
      preparation (n=58). The highest RCP value (i.e., 97.4%+/-0.5%, n=10) could be
      obtained immediately after an 8-s microwave heating time at 300 W (microwave
      temperature at 69 masculine C), and an average RCP value of 96.4%+/-1.3% (n=90)
      was maintained throughout the 24-h evaluation period. However, the trend seemed
      to reverse at higher microwave temperatures (i.e., 76 masculine-90 masculine C),
      which reconfirmed our initial findings that overheating had no benefit for the
      preparation of 99mTc-bicisate. To ensure that temperature was the only
      determining factor, a hot water incubator set at 69 masculine C was used (n=6).
      Similar RCP results were achieved. In conclusion, the use of a microwave oven at
      a low heat cycle provides a rapid and efficient way to prepare 99mTc-bicisate.

PMID- 9169574
TI  - A method for calibrating three-dimensional positron emission tomography without
      scatter correction.
AB  - Calibration for three-dimensional positron emission tomography (3D PET) using a
      uniform cylinder and cross-calibration with aliquots requires correction for
      scatter and attenuation. Thus the accuracy of the calibration is dependent on the
      scatter correction method, and on the applicability of the scatter correction for
      different regions of the body. A method has been developed which provides a
      calibration which does not require correction for scatter or attenuation, making
      it generally applicable and independent of the scatter correction. The method has
      been previously described for measurement of the absolute sensitivity of
      tomographic devices. This approach has been extended to give a calibration of the
      PET camera "in air" in units of kBq/pixel. The reconstructed images are
      multiplied by this factor to give accurate activity concentrations, after
      attenuation and scatter correction. The method has been used with a fully 3D
      filtered backprojection (reprojection) algorithm and iterative convolution
      subtraction scatter correction on data from an ECAT 953B. Using this method 3D
      PET images have been calibrated to within +/-5% accuracy, but this is highly
      dependent on the accuracy of the scatter correction. The method described here is
      practical and provides a means of calibrating a 3D PET system without the need
      for correction for scatter or attenuation of the calibration data.

PMID- 9169575
TI  - Discrepancy between blood flow and muscarinic receptor distribution in rat brain
      after middle cerebral artery occlusion.
AB  - To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a
      viable muscarinic neuronal marker which provides therapeutic information
      different from perfusional information in global brain, we evaluated the
      discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its
      five subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic
      (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham
      operated controls (n=6). In the acute phase, regional CBF was markedly reduced in
      the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only
      slightly. In the chronic phase, mAChR was reduced markedly in the infarcted
      lesion and the mRNA was also reduced. The mAChR was slightly reduced in the
      ipsilateral substantia nigra and pontine nucleus because of remote effects;
      however, regional CBF in the substantia nigra was slightly increased and did not
      change in the pontine nucleus. The discrepancy between CBF and mAChR was
      clarified, and the tendency toward a reduction in mRNA in the acute ischaemic
      region without a reduction in mAChR suggested the presence of cholinergic neurons
      which were viable but hypometabolic. It is concluded that mAChR imaging may be of
      value for the assessment of the viable cholinergic neuron density in vivo.

PMID- 9169576
TI  - Demonstration of decreased posterior cingulate perfusion in mild Alzheimer's
      disease by means of H215O positron emission tomography.
AB  - Although decreased posterior cingulate metabolism in Alzheimer's disease (AD) has
      been previously reported, there have been no reports on posterior cingulate
      perfusion. In this study we evaluated posterior cingulate perfusion as a relative
      value using statistical parametric maps (SPMs) and as an absolute value using
      conventional region of interest (ROI) settings. Twenty-eight subjects, including
      14 patients with mild AD (mean age: 66.4+/-12.1 years) and 14 normal controls
      (65.9+/-7.3 years) were studied. Regional cerebral blood flow (CBF) was measured
      with H215O and positron emission tomography (PET). In the SPM analysis, the left
      posterior cingulate and left parietotemporal CBFs were significantly decreased in
      the patients with mild AD (P<0.001). At a lower statistical threshold (P<0.05),
      the right posterior cingulate and right parietotemporal CBFs were also
      significantly decreased in the AD patients. In the ROI studies, the left parietal
      and posterior cingulate CBFs in the patients with mild AD were significantly
      lower than those of the normal controls by analysis of variance and post-hoc
      Scheffe's test (P<0.001). We conclude that posterior cingulate perfusion is
      decreased in mild AD, reflecting the pathological changes and metabolic reduction
      in the posterior cingulate gyrus that have previously been reported to occur in
      mild AD.

PMID- 9169577
TI  - Assessment of endogenous dopamine release by methylphenidate challenge using
      iodine-123 iodobenzamide single-photon emission tomography.
AB  - This double-blind, placebo-controlled study assessed pharmacologically induced
      endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in
      endogenous DA release after injection of the psychostimulant drug methylphenidate
      were evaluated by single-photon emission tomography (SPET) and constant infusion
      of iodine-123 iodobenzamide ([123I]IBZM), a D2 receptor radioligand that is
      sensitive to endogenous DA release. Methylphenidate induced displacement of
      striatal [123I]IBZM binding, resulting in a significantly decrease in the
      specific to non-specific [123I]IBZM uptake ratio (average: 8.6%) in comparison
      with placebo (average: -1.9%). Moreover, injection of methylphenidate induced
      significant behavioural responses on the following items: excitement, anxiety,
      tension, and mannerisms and posturing. The results of this study demonstrate the
      feasibility of using constant infusion of [123I]IBZM and SPET imaging to measure
      endogenous DA release after methylphenidate challenge and to investigate
      neurochemical aspects of behaviour.

PMID- 9169578
TI  - Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential
      diagnosis of pancreatic carcinoma: a report of 106 cases.
AB  - The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron
      emission tomography ([18F]FDG PET) as a tool for the differential diagnosis of
      pancreatic carcinoma while taking into account serum glucose level. A group of
      106 patients with unclear pancreatic masses were recruited for the study. PET was
      performed following intravenous administration of an average of 190 MBq [18F]FDG.
      Focally increased glucose utilisation was used as the criterion of malignancy. In
      addition, the "standardised uptake value" (SUV) was determined 45 min after
      injection. Carcinoma of the pancreas was demonstrated histologically in 74 cases,
      and chronic pancreatitis in 32 cases. Employing visual evaluation, 63 of the 74
      (85%) pancreatic carcinomas were identified by PET. In 27 of the 32 cases (84%)
      of chronic pancreatitis it was possible to exclude malignancy. False-negative
      results (n=11) were obtained mostly in patients with raised serum glucose levels
      (10 out of 11), and false-positives (n=5) in patients with inflammatory processes
      of the pancreas. Thus PET showed an overall sensitivity of 85%, a specificity of
      84%, a negative predictive value of 71%, and a positive predictive value of 93%.
      In a subgroup of patients with normal serum glucose levels (n=72), the results
      were 98%, 84%, 96% and 93%, respectively. Quantitative assessment yielded a mean
      SUV of 6.4+/-3.6 for pancreatic carcinoma as against a value of 3.6+/-1.7 for
      chronic pancreatitis (P<0.001), without increasing the diagnostic accuracy. This
      shows PET to be of value in assessing unclear pancreatic masses. The diagnostic
      accuracy of PET examinations is very dependent on serum glucose levels.

PMID- 9169579
TI  - The child in diagnostic nuclear medicine.

PMID- 9169580
TI  - Does fluorine-18 fluorodeoxyglucose metabolic imaging of tumours benefit
      oncology?
AB  - Fluoro-deoxyglucose (FDG) is a metabolic marker, which follows the same route
      into cells as that of glucose, and it can be radiolabelled with fluorine-18, 18F
      FDG making it suitable for imaging with positron emission tomography (PET). The
      fact that rapidly proliferating cells such as tumour cells accumulate 18F-FDG
      more avidly than those with a normal turnover rate has given rise to its
      potential in oncology. The rationale and previous published uses of 18F-FDG in
      oncology are reviewed, together with the various analysis techniques and
      associated methodological difficulties.

PMID- 9169581
TI  - Xist RNA is associated with the transcriptionally inactive XY body in mammalian
      male meiosis.
AB  - In eutherian mammals, X inactive-specific transcripts (Xist) are expressed in
      somatic cells possessing more than one X chromosome, and in germline cells of
      males, in which the single X chromosome is transcriptionally inactive. In early
      meiosis of males the sex chromosomes form an inactive XY nuclear compartment (XY
      body). We show by in situ reverse-transcribed polymerase chain reaction that Xist
      RNA is concentrated in the XY body. This fine localization suggests that Xist RNA
      is involved in inactivation of the male X chromosome, and that it has spreading
      capability, not only in cis but also in a quasi-cis mode, to juxtaposed non-X
      chromosomes. A hypothetical scheme links the evolution of heteromorphic sex
      chromosomes to the development of X condensation/inactivation in the male. The
      mechanism of X inactivation in somatic cells of mammalian females, resulting in
      male/female dosage compensation, has been recruited from the Xist-activated
      chromosome condensation machinery that developed in male meiosis earlier in
      evolution.

PMID- 9169582
TI  - Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres
      in mitosis.
AB  - Some autoimmune sera containing anticentromere autoantibodies also recognize a
      doublet of Mr 23 000 (p23) and 25 000 (p25) in addition to CENP (centromere
      protein)-A (Mr 19 000), -B (Mr 80 000), and -C (Mr 140 000). A p25 antigen
      (HP1(Hsalpha)) has been shown to be a human homolog of Drosophila HP1
      (heterochromatin protein 1). We have isolated a cDNA clone encoding another form
      of p25 (HP1(Hsbeta ) or p25beta) from a lambdaZap HepG2 library using human
      autoimmune serum. The deduced amino acid sequence of the clone contained a
      conserved chromodomain (chromatin modifier domain) in the N-terminal region and a
      heterochromatin binding domain in the C-terminal region. In immunofluorescence
      experiments, only affinity purified antibodies reactive with the C-terminal
      (amino acids 70-185) domain showed nucleoplasmic and heterochromatin staining,
      whereas N-terminal (amino acids 1-115) specific antibodies were nonreactive. In
      metaphase chromosome spreads, the C-terminal domain antibody was also localized
      to the centromeric regions of chromosomes. Association with centromeres was most
      prominent at anaphase and changed to a more generalized association with whole
      chromosomes in telophase. The cooccurrence of autoantibodies to centromere
      proteins and HP1 in certain autoimmune diseases might be a reflection of
      coordinated immune responses to these closely associated sets of proteins.

PMID- 9169583
TI  - The glutamate dehydrogenase, E74 and putative actin gene loci in the Drosophila
      montium subgroup. Chromosomal homologies among the montium species and D.
      melanogaster.
AB  - DNA-specific sequences from an enzyme-coding gene (glutamate dehydrogenase, gdh),
      a regulatory protein-coding gene (E74) and genes of the actin family were mapped
      by in situ hybridization on the polytene chromosomes of six species
      representative of the geographical distribution of the Drosophila montium
      subgroup of the melanogaster species group. In all species studied, one
      hybridization signal was detected for the gdh and E74 genes, and seven signals
      for the actin genes. The distribution of the actin-related loci in five montium
      species is similar to that of the other Drosophila species studied so far,
      although they present an extra signal. This distribution differs in the sixth
      montium species studied, D. kikkawai. Taking into account the present results, as
      well as previous data obtained mainly by in situ hybridizations, homologies among
      the polytene chromosomes of the montium subgroup species, as well as between
      these species and D. melanogaster, were also established.

PMID- 9169584
TI  - Roles of rDNA spacer and transcription unit-sequences in X-Y meiotic chromosome
      pairing in Drosophila melanogaster males.
AB  - Meiotic pairing of the X and Y chromosomes in Drosophila melanogaster males is
      mediated by the rDNA repeats, which are present in two tandem clusters, one in
      the centric X heterochromatin and the other near the base of the short arm of the
      Y chromosome. Deletion of the X chromosomal rDNA cluster disrupts X-Y pairing and
      causes high frequences of X-Y nondisjunction. Pairing can be partly restored by
      insertions of cloned complete rRNA genes or by rDNA fragments that include the
      intergenic spacer (IGS) region. A 240 bp repeated sequence in the IGS was shown
      to be effective in promoting pairing when present at copy numbers above five.
      This study further defines the rDNA sequences involved in mediating pairing.
      Germline insertions of a P element construct containing most of the rDNA
      transcription unit but no promoter or IGS region were obtained. Two single-copy
      insertions and four two-copy insertions proved unable to stimulate X-Y
      disjunction when located on an rDNA-deficient X chromosome. In addition, three
      insertions of a P element construct consisting of the IGS and promoter regions of
      the rDNA were characterized molecularly. These three insertions had previously
      been shown to range in pairing ability from very weak to quite strong. Molecular
      analysis revealed that the three insertions also vary in copy number of the 240
      bp IGS repeat and that these structural differences correlate with the
      differences in pairing ability. These data indicate that 240 bp repeats are
      considerably more effective than other regions of the rDNA in stimulating
      chromosome pairing.

PMID- 9169585
TI  - Chromosomal evolution of the Chinese muntjac (Muntiacus reevesi).
AB  - The aim of this study was to test the validity of the hypothesis that the 2n=46
      karyotype of the Chinese muntjac (Muntiacus reevesi) could have evolved through
      12 tandem fusions from a 2n=70 hypothetical ancestral karyotype, which is still
      retained in Chinese water deer (Hydropotes inermis) and brown-brocket deer
      (Mazama gouazoubira). Combining fluorescence-activated chromosomal sorting and
      degenerate oligonucleotide-primed polymerase chain reaction, we generated
      chromosome-specific DNA paint probes for 13 M. gouazoubira chromosomes and most
      of the M. reevesi chromosomes with the exception of 18, 19 and X. These paint
      probes were used for fluorescence in situ hybridisation to chromosomal
      preparations of M. reevesi, H. inermis and M. gouazoubira. Chromosome-specific
      paint probes from M. reevesi chromosomes 1-5 and 11 each delineated more than one
      homologous pair (18 pairs in total) on the metaphases of H. inermis and M.
      gouazoubira. All the other probes from M. reevesi and probes from M. gouazoubira
      each hybridised to one pair of homologous chromosomes or regions. The C5 probe,
      derived from centromeric satellite sequences of M. reevesi, hybridised to the
      centromeric regions of all chromosomes of these three species. Most
      interestingly, several non-random interstitial signals, which are apparently
      localised to the putative fusion points, were found on chromosomes 1-5 and 11 of
      M. reevesi. Both the reciprocal painting patterns and localisation of the C5
      probe demonstrate that M. reevesi chromosomes 1-5 and 11 could have evolved from
      18 different ancestral chromosomes through 12 tandem fusions, thus providing
      direct molecular cytogenetic support for the tandem fusion hypothesis of
      karyotype evolution in M. reevesi.

PMID- 9169586
TI  - Uniparental chromosome elimination in the early embryogenesis of the inviable
      salmonid hybrids between masu salmon female and rainbow trout male.
AB  - Chromosome elimination through chromosome loss and partial deletion is known to
      be one of the causes of embryonic inviability in some salmonid interspecific
      hybrids. Using fluorescence in situ hybridization and related techniques,
      including whole chromosome painting and comparative genomic hybridization,
      parental origin of eliminated chromosomes was identified in the inviable hybrids
      between masu salmon (Ms, Oncorhynchus masou) female and rainbow trout (Rb, O.
      mykiss) male at the early embryonic stage prior to death. In these hybrids, the
      haploid Rb chromosome number decreased to nearly half, whereas the Ms chromosomes
      were retained as one or occasionally two full haploid complements. The Rb
      chromosomes were also involved in the frequently observed fragments and
      micronuclei. Whereas the occurrence of fragments was constant throughout the
      observed period, chromosome loss occurred mainly from just after fertilization to
      the blastulae stage. In tissue sections and cell spreads of late blastula, some
      Rb chromosomes were trapped in the midzone from ana- to telophase, resulting in
      micronuclei at the subsequent interphase. Micronuclei and mitotic abnormalities
      were also observed in the androgenetic haploid hybrids. However, such
      abnormalities were seldom or never observed in the viable reciprocal hybrids. The
      present findings suggest that the paternal Rb chromosomes in the inviable hybrids
      are preferentially eliminated through mitotic abnormalities during early
      embryogenesis, owing to a possible incompatibility between the maternal Ms
      cytoplasm and paternal Rb genome.

PMID- 9169587
TI  - Genomic organization and phylogenetic relationships in the genus Dasypyrum
      analysed by southern and in situ hybridization of total genomic and cloned DNA
      probes.
AB  - Molecular cytogenetic methods have been used to study the controversial
      phylogenetic relationships between the species Dasypyrum villosum (L.) Candargy
      (2n=2x=14) and D. breviaristatum (Lindb. f.) Frederiksen (2n=4x=28). Using total
      genomic DNA from the two species as probes for in situ hybridization to
      chromosomes, we found that the pericentromeric regions of the chromosome arms of
      both species are similar, while distal regions show substantial differences. Two
      dispersed repetitive DNA sequences were isolated: pDbKB45 is distributed along
      the chromosomes but amplified in the subtelomeric regions of D. breviaristatum
      chromosomes, while pDbKB49, in both species, is less amplified in terminal
      regions. Size-separated restriction enzyme digests of DNA showed many repetitive
      fragments, but few in common between the two species. After probing Southern
      transfers with D. breviaristatum genomic DNA, all lanes showed similar
      hybridization patterns although one extra small band was evident in the D.
      breviaristatum lanes. In contrast, probing with D. villosum DNA showed very
      substantial differences between the two species. Genomic in situ hybridization to
      meiotic metaphases from an interspecific hybrid showed seven bivalents of D.
      breviaristatum origin and seven univalents from D. villosum. We also analysed the
      physical organization of 5S rDNA, 18S-25S rDNA and a tandemly repeated sequence
      from rye. Our data support an autotetraploid origin for D. breviaristatum, but
      its genome and that of D. villosum show extensive differences, so the tetraploid
      is unlikely to be directly derived from D. villosum.

PMID- 9169589
TI  - Evidence for a conserved binding motif of the dinuclear metal site in mammalian
      and plant purple acid phosphatases: 1H NMR studies of the di-iron derivative of
      the Fe(III)Zn(II) enzyme from kidney bean.
AB  - The di-iron core of mammalian purple acid phosphatases has been reproduced in the
      plant enzyme from kidney bean (Mr 111000) upon insertion of an Fe(II) ion in
      place of the native zinc(II) in the dinuclear Fe(III)Zn(II) core. The shortening
      of the electronic relaxation time of the metal centre allows detection of
      hyperfine-shifted 1H NMR resonances, although severe broadening due to Curie
      relaxation prevents independent signal assignment. Nevertheless, comparison of
      the spectral features of the structurally characterized plant enzyme with those
      of the mammalian species, which were previously extensively assigned, is
      consistent with a close similarity of the metal-binding sites, also suggested by
      previous sequence-alignment studies. Some differences appear to be mainly
      localized at the M(II) site. Spectral comparison was also carried out on the
      Fe(III)Co(II) derivatives.

PMID- 9169590
TI  - Phosphatidylinositol 3,5-bisphosphate defines a novel PI 3-kinase pathway in
      resting mouse fibroblasts.
AB  - PtdIns(3,5)P2 is identified as the product of an agonist-independent, wortmannin
      sensitive pathway in resting mouse cells. Results are presented here to indicate
      that PtdIns(3,5)P2 is formed by phosphorylation of PtdIns3P at the D-5 position,
      and they suggest that relatively constant cellular levels of PtdIns3P and
      PtdIns(3, 5)P2 are maintained by the concerted action of PtdIns3P 5-kinase and
      PtdIns(3,5)P2 5-phosphatase. These studies imply a novel mechanism for the action
      of PtdIns-specific phosphoinositide 3-hydroxykinases in mammalian cells.

PMID- 9169591
TI  - Modified proenzymes as artificial substrates for proteolytic enzymes:
      colorimetric assay of bacterial collagenase and matrix metalloproteinase activity
      using modified pro-urokinase.
AB  - We describe a new principle for assessment of the activity of proteolytic enzymes
      of all classes and show the application of this principle for the quantitative
      assay of bacterial collagenase and human matrix metalloproteinases (MMPs).
      Central to this new principle is the presence of a proenzyme that can be
      activated into an active enzyme by a single proteolytic event. The regular
      activation sequence in the proenzyme is replaced using protein engineering by an
      artificial sequence recognized by the proteinase to be determined. The latter can
      act as an activator for the newly engineered proenzyme. In the present paper a
      simple colorimetric assay for the determination for MMPs is described based on
      this principle. With the aid of protein engineering, a modified pro-urokinase has
      been prepared in which the activation sequence normally recognized by plasmin
      (Pro-Arg-Phe-Lys upward arrowIle-Ile-Gly-Gly) has been replaced by a sequence
      expected to be recognized and hydrolysed by many MMPs (Arg-Pro-Leu-Gly upward
      arrowIle-Ile-Gly-Gly). The active urokinase resulting from activation of the
      modified pro-urokinase by a MMP could be measured either directly, using a
      specific chromogenic peptide substrate for urokinase, or indirectly via urokinase
      catalysed plasminogen activation. The response of the assay to equal molar
      quantities of active MMPs decreases in the order MMP-2>MMP-9>MMP-1>MMP-3>MMP-7.
      The detection limit for MMP-9 was below 15 pM, corresponding to 3. 75x10(-15) mol
      per assay. Using the assay, increased MMP activity was detected in synovial
      tissue extracts from rheumatoid arthritis patients compared with those from
      osteoarthritis patients, and in stomach tumour extracts as compared with normal
      stomach tissue extracts.

PMID- 9169588
TI  - Regulated phosphorylation and dephosphorylation of tau protein: effects on
      microtubule interaction, intracellular trafficking and neurodegeneration.
AB  - This review attempts to summarize what is known about tau phosphorylation in the
      context of both normal cellular function and dysfunction. However, conceptions of
      tau function continue to evolve, and it is likely that the regulation of tau
      distribution and metabolism is complex. The roles of microtubule-associated
      kinases and phosphatases have yet to be fully described, but may afford insight
      into how tau phosphorylation at the distal end of the axon regulates cytoskeletal
      membrane interactions. Finally, lipid and glycosaminoglycan modification of tau
      structure affords yet more complexity for regulation and aggregation. Continued
      work will help to determine what is causal and what is coincidental in
      Alzheimer's disease, and may lead to identification of therapeutic targets for
      halting the progression of paired helical filament formation.

PMID- 9169592
TI  - Role of the 5' enhancer of the glutamine synthetase gene in its organ-specific
      expression.
AB  - In mammals, glutamine synthetase (GS) is expressed in a large number of organs,
      but the precise regulation of its expression is still obscure. Therefore a
      detailed analysis of the activity of the upstream regulatory element of the GS
      gene in the transcriptional regulation of its expression was carried out in
      transgenic mice carrying the chloramphenicol acetyltransferase (CAT) gene under
      the control of the upstream regulatory region of the GS gene. CAT and GS mRNA
      expression were compared in liver, epididymis, lung, adipocytes, testis, kidney,
      skeletal muscle and gastrointestinal tract, both quantitatively by ribonuclease
      protection analysis and topographically by in situ hybridization. It was found
      that the upstream regulatory region is active with respect both to the level and
      to the topography of GS gene expression in liver, epididymis, gastrointestinal
      tract (stomach, small intestine and colon) and skeletal muscle. On the other
      hand, in the kidney, brain, adipocytes, spleen, lung and testis, GS gene
      expression is not or only partly regulated by the 5' enhancer. A second enhancer,
      identified within the first intron, may regulate GS expression in the latter
      organs. Furthermore, CAT expression in the brain did not co-localize with that of
      GS, showing that the 5' regulatory region of the GS gene does not direct its
      expression to the astrocytes.

PMID- 9169593
TI  - Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen
      activated protein kinase and casein kinase in the cell nucleus: a possible role
      in the regulation of gene expression.
AB  - After insulin receptor activation, many cytoplasmic enzymes, including mitogen
      activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II
      (CKII) are activated, but exactly how insulin signalling progresses to the
      nucleus remains poorly understood. In Chinese hamster ovary cells overexpressing
      human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK
      II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm,
      in the unstimulated state. Nuclear localization of MAP kinase is also observed in
      3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found
      in the nucleus only in Fao and CHO cells. Insulin treatment for 5-30 min induces
      a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases
      and CKII are not translocated into the nucleus in response to insulin during this
      period. However, nuclear MAP kinase and CKII activities increase by 2-3-fold
      within 1-10 min after stimulation with insulin. By using gel-shift assays, it has
      been shown that insulin also stimulates nuclear protein binding to an AP-1 site
      with kinetics similar to MEK translocation and MAP kinase and CKII activation.
      Treatment of the extracts in vitro with protein phosphatase 2A or treatment of
      the intact cells with 5, 6-dichloro-1-beta-d-ribofuranosylbenzimidazole, a cell
      permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA
      binding activity, whereas incubation of cells with a MEK inhibitor produces only
      a slight decrease. These results suggest that insulin signalling results in the
      activation of serine kinases in the nucleus via two pathways: (1) insulin
      stimulates the nuclear translocation of some kinases, such as MEK, which might
      directly phosphorylate nuclear protein substrates or activate other nuclear
      kinases, and (2) insulin activates nuclear kinases without translocation. The
      latter is true of CKII, which seems to regulate the binding of nuclear proteins
      to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors.

PMID- 9169594
TI  - Modification of the N-terminus of human factor IX by defective propeptide
      cleavage or acetylation results in a destabilized calcium-induced conformation:
      effects on phospholipid binding and activation by factor XIa.
AB  - The propeptide of human coagulation factor IX (FIX) directs the gamma
      carboxylation of the first 12 glutamic acid residues of the mature protein into
      gamma-carboxyglutamic acid (Gla) residues. The propeptide is normally removed
      before secretion of FIX into the blood. However, mutation of Arg-4 in the
      propeptide abolishes propeptide cleavage and results in circulating profactor IX
      in the blood. We studied three such genetic variants, factor IX Boxtel (Arg-4-
      >Trp), factor IX Bendorf (Arg-4-->Leu) and factor IX Seattle C (Arg-4-->Gln).
      These variant profactor IX molecules bind normally to anti-FIX:Mg(II) antibodies,
      which indicates that the mutations do not seriously affect gamma-carboxylation.
      Metal ion titration of the binding of variant profactor IX to conformation
      specific antibodies demonstrates that the calcium-induced conformation is
      destabilized in the variant molecules. Also the binding of FIX Boxtel to
      phospholipids and its activation by factor XIa requires a high (>5 mM) calcium
      concentration. The three-dimensional structure of the Gla domain of FIX in the
      presence of calcium indicates that the acylation of the amino-terminus, rather
      than the presence of the propeptide, was responsible for the destabilization of
      the calcium-induced conformation. In order to confirm this, the alpha-amino group
      of Tyr1 of FIX was acetylated. This chemically modified FIX showed a similar
      destabilization of the calcium-induced conformation to variant profactor IX. Our
      data imply that the amino-terminus of FIX plays an important role in stabilizing
      the calcium-induced conformation of the Gla domain of FIX. This conformation is
      important for the binding to phospholipids as well as for the activation by
      factor XIa. Our results indicate that mutations in FIX that interfere with
      propeptide cleavage affect the function of the protein mainly by destabilizing
      the calcium-induced conformation.

PMID- 9169595
TI  - Evidence of ectokinase-mediated phosphorylation of osteopontin and bone
      sialoprotein by osteoblasts during bone formation in vitro.
AB  - Osteopontin (OPN) and bone sialoprotein (BSP) are phosphorylated glycoproteins
      that, together with osteonectin/secreted protein, acidic, rich in cysteine
      (SPARC) and osteocalcin, comprise the major non-collagen proteins of bone.
      Although phosphorylation of OPN and BSP, which is known to influence the
      biological properties of these proteins, has been shown to occur intracellularly,
      recent studies have demonstrated ectokinase activity in bone cell populations
      [Mikuni-Takagaki, Kakai, Satoyoshi, Kawano, Suzuki, Kawase and Saito (1995) J.
      Bone Miner. Res. 10, 231-241]. To determine whether OPN and BSP are
      phosphorylated by ectokinase activity we have used [gamma-32P]ATP and [gamma
      32P]GTP as cell-impenetrable phosphate donors to analyse for ectokinase activity
      in osteoblastic UMR106.06 cells and fetal rat calvarial cells (FRCCs). By pulse
      labelling confluent cells with radiolabelled nucleotides, the phosphorylation of
      endogenous and exogenously added OPN and BSP was demonstrated together with the
      labelling of a number of cell surface proteins. These phosphorylation reactions
      were inhibited by a cell-impermeable ectokinase inhibitor, K252b, and cell
      surface phosphorylation was also inhibited by exogenously added OPN and BSP
      substrates, indicating competition for the ectokinase enzyme. However,
      phosphorylation of OPN and BSP, both of which can mediate cell attachment through
      Arg-Gly-Asp (RGD) motifs, was not inhibited by an RGD peptide, suggesting that
      binding of OPN and BSP to cell surface integrins is not required. In similar
      experiments, ectokinase-mediated phosphorylation of OPN and BSP was demonstrated
      during mineralized tissue formation by FRCCs in vitro. These studies demonstrate
      that OPN and BSP secreted by bone cells are phosphorylated by a casein kinase II
      like ectokinase present on the surface of osteoblastic cells.

PMID- 9169596
TI  - Carrier-mediated transport of uridine diphosphoglucuronic acid across the
      endoplasmic reticulum membrane is a prerequisite for UDP-glucuronosyltransferase
      activity in rat liver.
AB  - UDP-glucuronosyltransferases (EC 2.4.1.17) is an isoenzyme family located
      primarily in the hepatic endoplasmic reticulum (ER) that displays latency of
      activity both in vitro and in vivo, as assessed respectively in microsomes and in
      isolated liver. The postulated luminal location of the active site of UDP
      glucuronosyltransferases (UGTs) creates a permeability barrier to aglycone and
      UDP-GlcA access to the enzyme and implies a requirement for the transport of
      substrates across the ER membrane. The present study shows that the recently
      demonstrated carrier-mediated transport of UDP-GlcA across the ER membrane is
      required and rate-limiting for glucuronidation in sealed microsomal vesicles as
      well as in the intact ER of permeabilized hepatocytes. We found that in both
      microsomes and permeabilized hepatocytes a gradual inhibition by N-ethylmaleimide
      (NEM) of UDP-GlcA transport into the ER produced a correspondingly increasing
      inhibition of 4-methylumbelliferone glucuronidation. That NEM selectively
      inhibited the UDP-GlcA transporter, without affecting intrinsic UGT activity, was
      demonstrated by showing that NEM had no effect on glucuronidation in microsomes
      or hepatocytes with permeabilized ER membrane. Additional evidence that UDP-GlcA
      transport is rate-limiting for glucuronidation in sealed microsomal vesicles as
      well as in the intact ER of permeabilized hepatocytes was obtained by showing
      that gradual selective trans-stimulation of UDP-GlcA transport by UDP-GlcNAc, UDP
      Xyl or UDP-Glc in each case produced correspondingly enhanced glucuronidation.
      Such stimulation of transport and glucuronidation was inhibited completely by
      NEM, which selectively inhibited UDP-GlcA transport.

PMID- 9169597
TI  - Kinetics of low-density lipoprotein receptor activity in Hep-G2 cells: derivation
      and validation of a Briggs-Haldane-based kinetic model for evaluating receptor
      mediated endocytotic processes in which receptors recycle.
AB  - The process of receptor-mediated endocytosis for receptors that recycle to the
      cell surface in an active form can be considered as being kinetically analogous
      to that of a uni-substrate, uni-product enzyme-catalysed reaction. In this study
      we have derived steady-state initial-velocity rate equations for this process,
      based on classical Briggs-Haldane and King-Altman kinetic approaches to multi
      step reactions, and have evaluated this kinetic paradigm, using as a model system
      the low-density lipoprotein (LDL)-receptor-mediated endocytosis of the trapped
      label [14C]sucrose-LDL in uninduced, steady-state Hep-G2 cells. Using the derived
      rate equations, together with experimentally determined values for Bmax (123
      fmol/mg of cell protein), Kd (14.3 nM), the endocytotic rate constant ke
      (analogous to kcat; 0.163 min-1), Km (80 nM) and maximal internalization velocity
      (26.4 fmol/min per mg), we have calculated the ratio ke/Km (0.00204 nM-1.min-1),
      the bimolecular rate constant for LDL and LDL-receptor association (0. 00248 nM
      1.min-1), the first-order rate constant for LDL-LDL-receptor complex dissociation
      (0.0354 min-1), the total cellular content of LDL receptors (154 fmol/mg of cell
      protein), the intracellular LDL receptor concentration (30.7 fmol/mg of cell
      protein) and the pseudo-first-order rate constant for LDL receptor recycling
      (0.0653 min-1). Based on this mathematical model, the kinetic mechanism for the
      receptor-mediated endocytosis of [14C]sucrose-LDL by steady-state Hep-G2 cells is
      one of constitutive endocytosis via independent internalization sites that
      follows steady-state Briggs-Haldane kinetics, such that LDL-LDL-receptor
      interactions are characterized by a rapid-high-affinity ligand-receptor
      association, followed by ligand-receptor complex internalization that is rapid
      relative to complex dissociation, and by receptor recycling that is more rapid
      than complex internalization and that serves to maintain 80% of cellular LDL
      receptors on the cell surface in the steady-state. The consistency with which
      these quantitative observations parallel previous qualitative observations
      regarding LDL-receptor-mediated endocytosis, together with the high correlation
      between theoretical internalization velocities (calculated from determined rate
      constants) and experimental internalization velocities, underscore the validity
      of considering receptor-mediated endocytotic processes for recycling receptors in
      catalytic terms.

PMID- 9169599
TI  - Subunit interaction in mammalian aldolases.
AB  - Enzyme inactivation was utilized to study subunit interaction in the
      homotetrameric glycolytic enzyme, aldolase. Isoenzymes from rabbit liver and
      skeletal muscle were inactivated in the presence of Pi and d-glyceraldehyde-P to
      a maximum stoichiometry of one modification per aldolase subunit. Subunit
      modification increased net negative charge on each subunit surface and was used
      to resolve modified aldolase isoenzymes into various chromatographic species. A
      combination of anion-(Mono Q) and cation- (Mono S) exchange chromatography
      separated the modified aldolase homotetramers into three distinct enzyme
      populations: unchanged enzyme, fully modified enzyme corresponding to one ligand
      molecule incorporated per subunit and partially modified enzyme in which only one
      subunit out of four is modified. Both fully and partially modified species were
      devoid of catalytic activity. Activity loss through modification of a single
      subunit in both aldolase isoenzymes indicates tightly coupled communication
      between subunit active sites and suggests simple functional regulation of
      aldolases.

PMID- 9169598
TI  - Escherichia coli L-aspartate-alpha-decarboxylase: preprotein processing and
      observation of reaction intermediates by electrospray mass spectrometry.
AB  - The Escherichia coli panD gene, encoding l-aspartate-alpha-decarboxylase, was
      cloned by PCR, and shown to complement a panD mutant defective in beta-alanine
      biosynthesis. Aspartate decarboxylase is a pyruvoyl-dependent enzyme, and is
      synthesized initially as an inactive proenzyme (the pi-protein), which is
      proteolytically cleaved at a specific X-Ser bond to produce a beta-subunit with
      XOH at its C-terminus and an alpha-subunit with a pyruvoyl group at its N
      terminus, derived from the serine. The recombinant enzyme, as purified, is a
      tetramer, and comprises principally the unprocessed pi-subunit (of 13.8 kDa),
      with a small proportion of the alpha- and beta-subunits (11 kDa and 2.8 kDa
      respectively). Incubation of the purified enzyme at elevated temperatures for
      several hours results in further processing. Using fluorescein thiosemicarbazide,
      the completely processed enzyme was shown to contain three pyruvoyl groups per
      tetrameric enzyme. The presence of unchanged serine at the N-terminus of some of
      the alpha-subunits was confirmed by electrospray mass spectrometry (ESMS) and N
      terminal amino acid sequencing. A novel HPLC assay for aspartate decarboxylase
      was established and used to determine the Km and kcat for l-aspartate as 151+/-16
      microM and 0.57 s-1 respectively. ESMS was also used to observe substrate and
      product adducts trapped on the pyruvoyl group by sodium cyanoborohydride
      treatment.

PMID- 9169600
TI  - Diadenosine polyphosphate hydrolase from presynaptic plasma membranes of Torpedo
      electric organ.
AB  - The diadenosine polyphosphate hydrolase present in presynaptic plasma membranes
      from the Torpedo electric organ has been characterized using fluorogenic
      substrates of the form di-(1, N6-ethenoadenosine) 5',5'''-P1,Pn-polyphosphate.
      The enzyme hydrolyses diadenosine polyphosphates (ApnA, where n=3-5), producing
      AMP and the corresponding adenosine (n-1) 5'-phosphate, Ap(n-1). The Km values of
      the enzyme were 0.543+/-0.015, 0.478+/-0.043 and 0. 520+/-0.026 microM, and the
      Vmax values were 633+/-4, 592+/-18 and 576+/-45 pmol/min per mg of protein, for
      the etheno derivatives of Ap3A (adenosine 5',5'''-P1,P3-triphosphate), Ap4A
      (adenosine 5',5"'-P1,P4-tetraphosphate) and Ap5A (adenosine 5',5'''-P1,P5
      pentaphosphate) respectively. Ca2+, Mg2+ and Mn2+ are enzyme activators, with
      EC50 values of 0.86+/-0.11, 1.35+/-0.24 and 0.58+/-0.10 mM respectively. The
      fluoride ion is an inhibitor with an IC50 value of 1.38+/-0.19 mM. The ATP
      analogues adenosine 5'-tetraphosphate and adenosine 5'-[gamma-thio]triphosphate
      are potent competitive inhibitors and adenosine 5'-[alpha,beta
      methylene]diphosphate is a less potent competitive inhibitor, the Ki values being
      0.29+/-0.03, 0.43+/-0.05 and 7.18+/-0.8 microM respectively. The P2-receptor
      antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulphonic acid behaves as a
      non-competitive inhibitor with a Ki value of 29.7+/-3.1 microM, and also exhibits
      a significant inhibitory effect on Torpedo apyrase activity. The effect of pH on
      the Km and Vmax values, together with inhibition by diethyl pyrocarbonate,
      strongly suggests the presence of functional histidine residues in Torpedo
      diadenosine polyphosphate hydrolase. The enzyme from Torpedo shows similarities
      with that of neural origin from neurochromaffin cells, and significant
      differences compared with that from endothelial vascular cells.

PMID- 9169601
TI  - Decreased susceptibility to calpains of v-FosFBR but not of v-FosFBJ or v
      JunASV17 retroviral proteins compared with their cellular counterparts.
AB  - The c-Fos and c-Jun transcription factors are rapidly turned over in vivo. One of
      the multiple pathways responsible for their breakdown is probably initiated by
      calpains, which are cytoplasmic calcium-dependent cysteine proteases. The c-fos
      gene has been transduced by two murine oncogenic retroviruses called Finkel
      Biskis-Jenkins murine sarcoma virus (FBJ-MSV) and Finkel-Biskis-Reilly murine
      sarcoma virus (FBR-MSV); c-jun has been transduced by the chicken avian sarcoma
      virus 17 (ASV17) retrovirus. Using an in vitro degradation assay, we show that
      the mutated v-FosFBR, but not v-FosFBJ or v-JunASV17, is resistant to calpains.
      This property raises the interesting possibility that decreased sensitivity to
      calpains might contribute to the tumorigenic potential of FBR-MSV by allowing
      greater accumulation of the protein that it encodes in infected cells. It has
      also been demonstrated that resistance to cleavage by calpains does not result
      from mutations that have accumulated in the Fos moiety of the viral protein but
      rather from the addition of atypical peptide motifs at its both ends. This
      observation raises the interesting possibility that homologous regions in viral
      and cellular Fos either display slightly different conformations or are
      differentially accessible to interacting proteins.

PMID- 9169603
TI  - Biochemical characterization of the arginine-specific proteases of Porphyromonas
      gingivalis W50 suggests a common precursor.
AB  - Extracellular proteases of Porphyromonas gingivalis specific for arginyl peptide
      bonds are considered to be important virulence factors in periodontal disease. In
      order to determine the number, inter-relationship and kinetic properties of these
      proteases, extracellular enzymes with this peptide-bond specificity were purified
      and characterized from P. gingivalis W50. Three forms, which we denote RI, RI-A
      and RI-B, accounted for all of the activity in the supernatant. All three enzymes
      contain an alpha chain of approximately 54 kDa with the same N-terminal amino
      acid sequence. RI is a heterodimer of non-covalently linked alpha and beta chains
      which migrate to the same position on SDS/PAGE but which can be resolved by 8 M
      urea/PAGE. RI-A and RI-B are both monomeric, but the molecular mass of RI-B (70
      80 kDa) is significantly increased due to post-translational modification with
      lipopolysaccharide. All forms show absolute specificity for peptide bonds with
      Arg in the P1 position and are also capable of hydrolysing N-terminal Arg and C
      terminal Arg-Arg peptide bonds. Thus they show limited amino- and carboxy
      peptidase activity. For the hydrolysis of Nalpha-benzoyl-L-Arg-p-nitroanilide,
      the pH optimum is 8.0 at 30 degrees C. The Vmax for all three enzymes is
      controlled by ionization of two residues with apparent pKas at 30 degrees C of 6.
      5+/-0.05 and 9.7+/-0.05, and DeltaH values of approximately 29 kJ/mol and
      approximately 24 kJ/mol in the enzyme-substrate complex. By analogy with papain,
      the pKa of 6.5 could be ascribed to a Cys and the pKa of 9.7 to a His residue. E
      64 [L-trans-epoxysuccinyl-leucylamide-4-(4-guanidino)butane] is a competitive
      inhibitor of RI, RI-A and RI-B. Based on physical properties and kinetic
      behaviour, RI-A appears to be analogous to gingipain from P. gingivalis HG66.
      However the alpha/beta structure of RI differs significantly from that of the
      high-molecular-mass multimeric complex of gingipain containing four
      haemagglutinins described by others. Since the genes for RI and high-molecular
      mass gingipain are identical, the data indicate that an alternative processing
      pathway is involved in the formation of RI from the initial precursor.
      Furthermore, the identical N-termini and enzymic properties of the catalytic
      component of RI, RI-A and RI-B suggest that the maturation pathway of the RI
      precursor may also give rise to RI-A and RI-B. The physiological functions of
      these isoforms and their role in the disease process may become more apparent
      through examination of their interactions with host proteins.

PMID- 9169602
TI  - Diacylglycerol generated by exogenous phospholipase C activates the mitogen
      activated protein kinase pathway independent of Ras- and phorbol ester-sensitive
      protein kinase C: dependence on protein kinase C-zeta.
AB  - The role of diacylglycerol (DG) formation from phosphatidylcholine in mitogenic
      signal transduction is poorly understood. We have generated this lipid at the
      plasma membrane by treating Rat-1 fibroblasts with bacterial phosphatidylcholine
      specific phospholipase C (PC-PLC). This treatment leads to activation of mitogen
      activated protein kinase (MAPK). However, unlike platelet-derived growth factor
      (PDGF) or epidermal growth factor (EGF), PC-PLC fails to activate Ras and to
      induce DNA synthesis, and activates MAPK only transiently (<45 min). Down
      regulation of protein kinase C (PKC) -alpha, -delta and -epsilon isotypes has
      little or no effect on MAPK activation by either PC-PLC or growth factors.
      However, Ro 31-8220, a highly selective inhibitor of all PKC isotypes, including
      atypical PKC-zeta but not Raf-1, blocks MAPK activation by PDGF and PC-PLC, but
      not that by EGF, suggesting that atypical PKC mediates the PDGF and PC-PLC
      signal. In line with this, PKC-zeta is activated by PC-PLC and PDGF, but not by
      EGF, as shown by a kinase assay in vitro, using biotinylated epsilon-peptide as a
      substrate. Furthermore, dominant-negative PKC-zeta inhibits, while (wild-type)
      PKC-zeta overexpression enhances MAPK activation by PDGF and PC-PLC. The results
      suggest that DG generated by PC-PLC can activate the MAPK pathway independent of
      Ras and phorbol-ester-sensitive PKC but, instead, via PKC-zeta.

PMID- 9169604
TI  - Topology of carnitine palmitoyltransferase I in the mitochondrial outer membrane.
AB  - The topology of carnitine palmitoyltransferase I (CPT I) in the outer membrane of
      rat liver mitochondria was studied using several approaches. 1. The accessibility
      of the active site and malonyl-CoA-binding site of the enzyme from the cytosolic
      aspect of the membrane was investigated using preparations of octanoyl-CoA and
      malonyl-CoA immobilized on to agarose beads to render them impermeant through the
      outer membrane. Both immobilized ligands were fully able to interact effectively
      with CPT I. 2. The effects of proteinase K and trypsin on the activity and
      malonyl-CoA sensitivity of CPT I were studied using preparations of mitochondria
      that were either intact or had their outer membranes ruptured by hypo-osmotic
      swelling (OMRM). Proteinase K had a marked but similar effect on CPT I activity
      irrespective of whether only the cytosolic or both sides of the membrane were
      exposed to it. However, it affected sensitivity more rapidly in OMRM. By
      contrast, trypsin only reduced CPT I activity when incubated with OMRM. The
      sensitivity of the residual CPT I activity was unaffected by trypsin. 3. The
      proteolytic fragments generated by these treatments were studied by Western
      blotting using three anti-peptide antibodies raised against linear epitopes of
      CPT I. These showed that a proteinase K-sensitive site close to the N-terminus
      was accessible from the cytosolic side of the membrane. No trypsin-sensitive
      sites were accessible in intact mitochondria. In OMRM, both proteinase K and
      trypsin acted from the inter-membrane space side of the membrane. 4. The ability
      of intact mitochondria and OMRM to bind to each of the three anti-peptide
      antibodies was used to study the accessibility of the respective epitopes on the
      cytosolic and inter-membrane space sides of the membrane. 5. The results of all
      these approaches indicate that CPT I adopts a bitopic topology within the
      mitochondrial outer membrane; it has two transmembrane domains, and both the N-
      and C-termini are exposed on the cytosolic side of the membrane, whereas the
      linker region between the transmembrane domains protrudes into the intermembrane
      space.

PMID- 9169605
TI  - Sheep mast cell proteinase-1, a serine proteinase with both tryptase- and chymase
      like properties, is inhibited by plasma proteinase inhibitors and is mitogenic
      for bovine pulmonary artery fibroblasts.
AB  - Sheep mast cell proteinase-1 (sMCP-1), a serine proteinase with dual
      chymase/tryptase activity, is expressed in gastrointestinal mast cells, and
      released systemically and on to the mucosal surface during gastrointestinal
      nematode infection. The potential for native plasma proteinase inhibitors to
      control sMCP-1 activity was investigated. Sheep alpha1-proteinase inhibitor
      (alpha1PI) inhibited sMCP-1 slowly, with second-order association rate constant
      (kass) 1. 1x10(3) M-1.s-1, whereas sheep contrapsin inhibited trypsin (kass
      2.2x10(6) M-1.s-1) but not sMCP-1. Western-blot analysis and gel filtration
      showed that when added to serum or plasma, sMCP-1 was partitioned between
      alpha1PI and alpha2-macroglobulin. The possibility that significant cleavage of
      plasma proteins could occur before sMCP-1 was inhibited was investigated using
      gel filtration and SDS/PAGE after adding sMCP-1 to plasma. Cleavage of ovine
      fibrinogen occurred in the presence of excess alpha1PI and alpha2-macroglobulin,
      the alpha-chain being cleaved C-terminally and the beta-chain at the putative Lys
      27. In addition, sMCP-1 was found to be mitogenic for bovine pulmonary artery
      fibroblasts, but was not mitogenic in the presence of soya-bean trypsin
      inhibitor. In terms of fibrinogen cleavage and fibroblast stimulation, sMCP-1
      shows functional similarities to mast cell tryptase.

PMID- 9169606
TI  - Synthetic, structural and biological studies of the ubiquitin system: synthesis
      and crystal structure of an analogue containing unnatural amino acids.
AB  - Ubiquitin is a 76-amino acid protein involved in the targeting for destruction of
      proteins in the cell. The protein can readily be synthesized chemically affording
      an extra dimension to studies of protein stability. Ubiquitin with various
      modifications to the hydrophobic core has been synthesized. In particular, two
      core amino acids have been replaced by aminobutyric acid (Val-26) and norvaline
      (for Ile-30) and the product crystallized. The refined crystal structure shows an
      overall contraction of the molecule and the side chain of Nva-30 rotates relative
      to Ile-30. However, the side chain rotation is not sufficient to compensate for
      the effect of the loss of the methyl group and hence a small cavity is introduced
      into the structure, which decreases the stability of the protein. The biological
      behaviour of the modified protein is unaltered. The observed changes in stability
      are of the magnitude expected for the removal of methyl groups from the
      hydrophobic core of a protein. Interestingly, the effect appears to be
      independent of the position of the removed methyl group. The intact structure,
      but not its stability, is important for recognition by the biological conjugating
      system.

PMID- 9169607
TI  - Dissimilar interaction of factor VIII with endothelial cells and lipid vesicles
      during factor X activation.
AB  - A localized and regulated cascade of proteolytic events is a prerequisite for
      normal haemostasis. The activation of factor X by activated factor IX (factor
      IXa) in the presence of activated factor VIII (factor VIIIa) is essential for the
      formation of a fibrin clot at sites of vascular injury. We observed sustained
      activation of factor X on the surface of vascular endothelial cells, whereas, in
      agreement with others, on synthetic negatively charged phospholipid vesicles and
      activated blood platelets factor X activation is transient and starts to decline
      a few minutes after the onset of the reaction. We examined the mechanism
      responsible for these differences in factor X activation. Procoagulant membrane
      and solution were analysed separately for the occurrence of factor VIII and its
      activation fragments. On negatively charged phospholipid vesicles, on
      dissociation of factor VIIIa, the 67 kDa light-chain fragment remains associated
      with the lipid membrane. As a result, factor VIII-binding sites remain occupied,
      and dampening of factor X activation occurs. In contrast, on monolayers of
      endothelial cells, no residual factor VIIIa fragments associated with the cell
      membrane were observed. During endothelial-cell-mediated activation of factor X,
      accumulation of factor VIIIa fragments was observed in the solution phase only.
      This finding suggests that, on endothelial cells, factor VIII-binding sites
      remain accessible for further factor VIII binding, guaranteeing sustained
      activation of factor X. These data demonstrate that the nature of the
      procoagulant membrane contributes to the regulation of the cofactor activity of
      factor VIII and thereby affects the progress of factor X activation.

PMID- 9169608
TI  - Phosphorylation of tau by glycogen synthase kinase 3beta affects the ability of
      tau to promote microtubule self-assembly.
AB  - To study the effects of phosphorylation by glycogen synthase kinase-3beta (GSK
      3beta) on the ability of the microtubule-associated protein tau to promote
      microtubule self-assembly, tau isoform 1 (foetal tau) and three mutant forms of
      this tau isoform were investigated. The three mutant forms of tau had the
      following serine residues, known to be phosphorylated by GSK-3, replaced with
      alanine residues so as to preclude their phosphorylation: (1) Ser-199 and Ser-202
      (Ser-199/202-->Ala), (2) Ser-235 (Ser-235-->Ala) and (3) Ser-396 and Ser-404 (Ser
      396/404-->Ala). Wild-type tau and the mutant forms of tau were phosphorylated
      with GSK-3beta, and their ability to promote microtubule self-assembly was
      compared with the corresponding non-phosphorylated tau species. In the non
      phosphorylated form, wild-type tau and all of the mutants affected the mean
      microtubule length and number concentrations of assembled microtubules in a
      manner consistant with enhanced microtubule nucleation. Phosphorylation of these
      tau species with GSK-3beta consistently reduced the ability of a given tau
      species to promote microtubule self-assembly, although the affinity of the tau
      for the microtubules was not greatly affected by phosphorylation since the tau
      species remained largely associated with the microtubules. This suggests that the
      regulation of microtubule assembly can be controlled by phosphorylation of tau at
      sites accessible to GSK-3beta by a mechanism that does not necessarily involve
      the dissociation of tau from the microtubules.

PMID- 9169609
TI  - Subcellular localization and function of melanogenic enzymes in the ink gland of
      Sepia officinalis.
AB  - The ink gland of the cuttlefish Sepia officinalis has traditionally been regarded
      as a convenient model system for investigating melanogenesis. This gland has been
      shown to contain a variety of melanogenic enzymes including tyrosinase, a
      dopachrome-rearranging enzyme and peroxidase. However, whether and to what extent
      these enzymes co-localize in the melanogenic compartments and interact is an open
      question. Using polyclonal antibodies that recognize the corresponding Sepia
      proteins, we have been able to demonstrate that peroxidase has a different
      subcellular localization pattern from tyrosinase and dopachrome-rearranging
      enzyme. Whereas peroxidase is located in the rough endoplasmic reticulum and in
      the matrix of premelanosomes and melanosomes, tyrosinase and dopachrome
      rearranging enzyme are present in the rough endoplasmic reticulum-Golgi transport
      system, at the level of trans-Golgi cisternae, trans-Golgi network and coated
      vesicles, and in melanosomes on pigmented granules. These results fill a
      longstanding gap in our knowledge of the melanin-producing system in Sepia and
      provide the necessary background for dissection at the molecular level of the
      complex interaction between melanogenic enzymes. Moreover, the peculiar and
      complex organization of melanin in an invertebrate such as Sepia officinalis is
      surprising and could provide the basis for understanding the process in more
      evolved systems such as that of mammals.

PMID- 9169610
TI  - Molecular cloning and heterologous expression of the isopullulanase gene from
      Aspergillus niger A.T.C.C. 9642.
AB  - Isopullulanase (IPU) from Aspergillus niger A.T.C.C. (American Type Culture
      Collection) 9642 hydrolyses pullulan to isopanose. IPU is important for the
      production of isopanose and is used in the structural analysis of
      oligosaccharides with alpha-1,4 and alpha-1,6 glucosidic linkages. We have
      isolated the ipuA gene encoding IPU from the filamentous fungi A. niger A.T.C.C.
      9642. The ipuA gene encodes an open reading frame of 1695 bp (564 amino acids).
      IPU contained a signal sequence of 19 amino acids, and the molecular mass of the
      mature form was calculated to be 59 kDa. IPU has no amino-acid-sequence
      similarity with the other pullulan-hydrolysing enzymes, which are pullulanase,
      neopullulanase and glucoamylase. However, IPU showed a high amino-acid-sequence
      similarity with dextranases from Penicillium minioluteum (61%) and Arthrobacter
      sp. (56%). When the ipuA gene was expressed in Aspergillus oryzae, the expressed
      protein (recombinant IPU) had IPU activity and was immunologically reactive with
      antibodies raised against native IPU. The substrate specificity, thermostability
      and pH profile of recombinant IPU were identical with those of the native enzyme,
      but recombinant IPU (90 kDa) was larger than the native enzyme (69-71 kDa). After
      deglycosylation with peptide-N-glycosidase F, the deglycosylated recombinant IPU
      had the same molecular mass as deglycosylated native enzyme (59 kDa). This result
      suggests that the carbohydrate chain of recombinant IPU differed from that of the
      native enzyme.

PMID- 9169612
TI  - Characterization of the human multidrug resistance protein containing mutations
      in the ATP-binding cassette signature region.
AB  - A number of mutants with single amino acid replacements were generated in the
      highly conserved ATP-binding cassette (ABC)-signature region (amino acids 531
      543) of the N-terminal half of the human multidrug resistance (MDR1) protein. The
      cDNA variants were inserted into recombinant baculoviruses and the MDR1 proteins
      were expressed in Spodoptera frugiperda (Sf9) insect cells. The level of
      expression and membrane insertion of the MDR1 variants was examined by
      immunostaining, and MDR1 function was followed by measuring drug-stimulated
      ATPase activity. We found that two mutations, L531R and G534V, practically
      eliminated MDR1 expression; thus these amino acid replacements seem to inhibit
      the formation of a stable MDR1 protein structure. The MDR1 variants G534D and
      I541R were expressed at normal levels with normal membrane insertion, but showed
      a complete loss of drug-stimulated ATPase activity, while mutant R538M yielded
      full protein expression but with greatly decreased ATPase activity. Increasing
      the ATP concentration did not restore MDR1 ATPase activity in these variants.
      Some amino acid replacements in the ABC-signature region (K536I, K536R, I541T and
      R543S) affected neither the expression and membrane insertion nor the ATPase
      function of MDR1. We found no alteration in the drug-sensitivity of ATP cleavage
      in any of the MDR1 variants that had measurable ATPase activity. These
      observations suggest that the ABC-signature region is essential for MDR1 protein
      stability and function, but alterations in this region do not seem to modulate
      MDR1-drug interactions directly.

PMID- 9169611
TI  - Allosteric equilibrium model explains steady-state coupling of beta-adrenergic
      receptors to adenylate cyclase in turkey erythrocyte membranes.
AB  - We used a simple experimental approach to clarify some contradictory predictions
      of the collision coupling and equilibrium models (e.g. ternary complex, two-state
      ternary complex or quinternary complex), which describe G-protein-mediated beta
      adrenergic receptor signalling in essentially different manners. Analysis of the
      steady-state coupling of beta-adrenoceptors to adenylate cyclase in turkey
      erythrocyte membranes showed that: (1) in the absence of an agonist, Gpp(NH)p (a
      hydrolysis-resistant analogue of GTP) can activate adenylate cyclase very slowly;
      (2) this activity reaches a steady state in approx. 5 h, the extent of activity
      depending on the concentration of the nucleotide; (3) isoprenaline-activated
      steady-state adenylate cyclase can be inactivated by propranolol (a competitive
      antagonist that relaxes the receptor activation), in the presence of Gpp(NH)p
      (which provides a virtual absence of GTPase) and millimolar concentrations of
      Mg2+ (the rate of this inactivation is relatively fast); (4) increasing the
      concentration of Gpp(NH)p can saturate the steady-state activity of adenylate
      cyclase. The saturated enzyme activity was lower than that induced by
      isoprenaline under the same conditions. This additional agonist-induced
      activation was reversible. In the light of these results, we conclude that
      agonist can also activate the guanine nucleotide-saturated system in the absence
      of GTPase by a mechanism other than guanine nucleotide exchange. We explain these
      phenomena in the framework of a quinternary complex model as an agonist-induced
      and receptor-mediated dissociation of guanine nucleotide-saturated residual
      heterotrimer, the equilibrium concentration of which is not necessarily zero.
      These results, which suggest a continuous interaction between receptor and G
      protein, can hardly be accommodated by the collision coupling model that was
      originally suggested for the present experimental system and then applied to many
      other G-protein systems. Therefore we attempt to unify the equilibrium and
      collision coupling approaches to provide a consistent theoretical basis for the G
      protein-mediated beta-adrenergic receptor signalling in turkey erythrocyte
      membranes.

PMID- 9169613
TI  - Mitogen-activated protein kinase translocates to the nucleus during ischaemia and
      is activated during reperfusion.
AB  - Growth factors and various cellular stresses are known to activate mitogen
      activated protein (MAP) kinase, which plays a role in conveying signals from the
      cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a
      prerequisite for translocation. Here, we investigate the translocation and
      activation of MAP kinase during ischaemia and reperfusion in perfused rat heart.
      Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol
      fraction to the nuclear fraction. Immunohistochemical observation shows that MAP
      kinase staining in the nucleus is enhanced after ischaemia for 40 min.
      Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear
      fraction during ischaemia, indicating that unphosphorylated MAP kinase
      translocates from the cytosol to the nucleus. During reperfusion (0-30 min),
      after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear
      fraction is increased with a peak at 10 min of reperfusion. The activation is
      confirmed by MAP kinase activity with similar kinetics to the tyrosine
      phosphorylation. However, the amount of MAP kinase in the fraction is almost
      constant during reperfusion for 10 min. Although an upstream kinase for MAP
      kinase, MAP kinase/extracellular signal-regulated kinase kinase (MEK)-1, remains
      in the cytosol throughout ischaemia and reperfusion, MEK-2, another upstream
      kinase for MAP kinase, is constantly present in the nucleus as well as in the
      cytoplasm, based on analyses by fractionation and immunohistochemistry.
      Furthermore, MEK-2 activity in the nuclear fraction is rapidly increased during
      post-ischaemic reperfusion. These findings demonstrate that nuclear MAP kinase is
      activated by tyrosine phosphorylation during reperfusion, probably by MEK-2.

PMID- 9169615
TI  - Enhanced expression of glucose-6-phosphate dehydrogenase in human cells
      sustaining oxidative stress.
AB  - Recent reports have demonstrated that glucose-6-phosphate dehydrogenase (G6PD)
      activity in mammalian cells is necessary in order to ensure cell survival when
      damage is produced by reactive oxygen intermediates. In this paper we demonstrate
      that oxidative stress, caused by agents acting at different steps in the
      biochemical pathway controlling the intracellular redox status, determines the
      increase in G6PD-specific activity in human cell lines of different tissue
      origins. The intracellular level of G6PD-specific mRNA also increases, with
      kinetics compatible with the induction of new enzyme synthesis. We carried out
      experiments in which cells were exposed to oxidative stress in the presence of
      inhibitors of protein or RNA synthesis. These demonstrated that increased G6PD
      expression is mainly due to an increased rate of transcription, with a minor but
      significant contribution of regulatory mechanisms acting at post-transcriptional
      levels. These results provide new information on the defence systems that
      eukaryotic cells possess in order to prevent damage caused by potentially harmful
      oxygen derivatives.

PMID- 9169614
TI  - Biochemical characterization of the mouse muscle-specific enolase: developmental
      changes in electrophoretic variants and selective binding to other proteins.
AB  - The glycolytic enzyme enolase (EC 4.2.1.11) is active as dimers formed from three
      subunits encoded by different genes. The embryonic alphaalpha isoform remains
      distributed in many adult cell types, whereas a transition towards betabeta and
      gammagamma isoforms occurs in striated muscle cells and neurons respectively. It
      is not understood why enolase exhibits tissue-specific isoforms with very close
      functional properties. We approached this problem by the purification of native
      betabeta-enolase from mouse hindlimb muscles and by raising specific antibodies
      of high titre against this protein. These reagents have been useful in revealing
      a heterogeneity of the beta-enolase subunit that changes with in vivo and in
      vitro maturation. A basic carboxypeptidase appears to be involved in generating
      an acidic beta-enolase variant, and may regulate plasminogen binding by this
      subunit. We show for the first time that pure betabeta-enolase binds with high
      affinity the adjacent enzymes in the glycolytic pathway (pyruvate kinase and
      phosphoglycerate mutase), favouring the hypothesis that these three enzymes form
      a functional glycolytic segment. betabeta-Enolase binds with high affinity
      sarcomeric troponin but not actin and tropomyosin. Some of these binding
      properties are shared by the alphaalpha-isoenolase, which is also expressed in
      striated muscle, but not by the neuron-specific gammagamma-enolase. These results
      support the idea that specific interactions with macromolecules will address
      muscle enolase isoforms at the subcellular site where ATP, produced through
      glycolysis, is most needed for contraction. Such a specific targeting could be
      modulated by post-translational modifications.

PMID- 9169616
TI  - Delayed oxidative degradation of polyunsaturated diacyl phospholipids in the
      presence of plasmalogen phospholipids in vitro.
AB  - The oxidative degradation of plasmalogen (alkenylacyl) phospholipids was analysed
      in the absence and the presence of polyunsaturated ester phospholipids by 1H-NMR
      and by chemical determination. Brain lysoplasmenylethanolamine (lyso-P-PE), brain
      P-PE and erythrocyte P-PE, containing an increasing number of intrachain double
      bonds at sn2, were oxidized with 2,2'-azobis-(2-amidinopropane hydrochloride)
      (AAPH; 2 or 10 mM) in Triton X-100 micelles (detergent/phospholipid 1:5,
      mol/mol). The formation of two peroxyl radicals was accompanied by the
      degradation of approx. one molecule of brain lyso-P-PE. On oxidation of brain P
      PE or erythrocyte P-PE (320 nmol) with 2 mM AAPH, the (alpha-vinyl) methine 1H
      signal of the enol ether decreased more rapidly than the methine proton peak of
      intrachain double bonds. The rate of enol ether degradation increased in the
      order: erythrocyte P-PE>brain P-PE>brain lyso-P-PE. The disappearance of the
      polyunsaturated ester phospholipids 1-palmitoyl-2-arachidonoyl
      phosphatidylcholine (16:0/20:4-PC) and 1-palmitoyl-2-linoleoyl
      phosphatidylcholine (16:0/18:2-PC) (100 nmol), as induced by 10 mM AAPH, was
      nearly completely inhibited by the plasmalogens (25 nmol) in the first 30 and 60
      min of incubation respectively, and was delayed at later time points.
      Plasmalogens and vitamin E (4-25 nmol) mitigated the decreases in 16:0/[3H]20:4
      PC (100 nmol) induced by 2 mM AAPH in a similar manner. The initial rate of
      degradation of intrachain double bonds of 16:0/20:4-PC and 16:0/18:2-PC (320
      nmol; 2 mM AAPH) was decreased by 59% and 81% respectively in the presence of 80
      nmol of brain lyso-P-PE. In conclusion, plasmalogens markedly delay the oxidative
      degradation of intrachain double bonds under in vitro conditions. Interactions of
      enol ether double bonds with initiating peroxyl radicals as well as with products
      generated by prior oxidation of polyunsaturated fatty acids are proposed to be
      responsible for this capacity of plasmalogens. Furthermore, the products of enol
      ether oxidation apparently do not propagate the oxidation of polyunsaturated
      fatty acids.

PMID- 9169617
TI  - Isolated rat hepatocytes differentially bind and internalize bovine lactoferrin N
      and C-lobes.
AB  - Isolated rat hepatocytes bind and internalize bovine lactoferrin (Lf) and its
      bound iron in a Ca2+-dependent manner. In this study, we determined if one or
      both halves of Lf (N- and C-lobes) were responsible for the interaction of Lf
      with hepatocytes. We isolated three tryptic fragments of bovine Lf. Cleavage at
      Arg284-Ser285 generated two fragments: N-terminal pp36 that contained 80% of Lf N
      lobe and C-terminal pp51. A second cleavage at Arg338-Ala339 generated a smaller
      fragment (pp44) that contained all of the C-lobe with no N-lobe elements.
      Hepatocytes bound Lf and pp51 in a Ca2+-dependent manner with the same affinity
      (Kd approx. 75 nM) and to nearly identical extents (approx. 10(6) sites per
      cell). Lf and pp51 competed with each other for binding to cells over a similar
      titration range. Hepatocytes internalized Lf at a faster rate than pp51 (kin=0.28
      and 0.19 min-1 respectively), but cells degraded pp51 at approx. twice the rate
      of native Lf. pp44 competed with 125I-labelled Lf for binding to Ca2+-dependent
      binding sites on hepatocytes as well as native Lf or pp51. In contrast,
      hepatocytes bound pp36 (Kd=90 nM, <=5x10(6) sites per cell) but did not
      internalize or degrade it appreciably. Moreover, pp36 binding to cells was not
      Ca2+-dependent, and pp36 competed poorly with native Lf and pp51 for binding to
      cells. We conclude from these findings that the Lf determinants responsible for
      binding to the Ca2+-dependent receptor on hepatocytes is present within the C
      lobe of Lf.

PMID- 9169618
TI  - Identification of critical residues in the colicin E9 DNase binding region of the
      Im9 protein.
AB  - 1H-15N NMR studies, in conjunction with mutagenesis experiments, have been used
      to delineate the DNase-binding surface of the colicin E9 inhibitor protein Im9
      (where Im stands for immunity protein). Complexes were formed between the 15 kDa
      unlabelled E9 DNase domain and the 9.5 kDa Im9 protein uniformly labelled with
      15N. Approx. 90% of the amide resonances of the bound Im9 were assigned and
      spectral parameters obtained from 1H-15N heteronuclear single quantum coherence
      (HSQC) spectra were compared with those for the free Im9 assigned previously.
      Many of the amide resonances were shifted on complex formation, some by more than
      2 p.p.m. in the 15N dimension and more than 0.5 p.p.m. in the 1H dimension. Most
      of the strongly shifted amides are located on the surfaces of two of the four
      helices, helix II and helix III. Whereas helix II had already been identified
      through genetic and biochemical investigations as an important determinant of
      biological specificity, helix III had not previously been implicated in binding
      to the DNase. To test the robustness of the NMR-delineated DNase-binding site, a
      selection of Im9 alanine mutants were constructed and their dissociation rate
      constants from E9 DNase-immunity protein complexes quantified by radioactive
      subunit exchange kinetics. Their off-rates correlated well with the NMR
      perturbation analysis; for example, residues that were highly perturbed in HSQC
      experiments, such as residues 34 (helix II) and 54 (helix III), had a marked
      effect on the DNase-immunity protein dissociation rate when replaced by alanine.
      The NMR and mutagenesis data are consistent with a DNase-binding region on Im9
      composed of invariant residues in helix III and variable residues in helix II.
      The relationship of this binding site model to the wide range of affinities (Kd
      values in the range 10(-4) to 10(-16)M) that have been measured for cognate and
      non-cognate colicin DNase-immunity protein interactions is discussed.

PMID- 9169619
TI  - Effects of temperature and SDS on the structure of beta-glycosidase from the
      thermophilic archaeon Sulfolobus solfataricus.
AB  - The effects of temperature and SDS on the three-dimensional organization and
      secondary structure of beta-glycosidase from the thermophilic archaeon Sulfolobus
      solfataricus were investigated by CD, IR spectroscopy and differential scanning
      calorimetry. CD spectra in the near UV region showed that the detergent caused a
      remarkable change in the protein tertiary structure, and far-UV CD analysis
      revealed only a slight effect on secondary structure. Infrared spectroscopy
      showed that low concentrations of the detergent (up to 0.02%) induced slight
      changes in the enzyme secondary structure, whereas high concentrations caused the
      alpha-helix content to increase at high temperatures and prevented protein
      aggregation.

PMID- 9169620
TI  - The ATP synthase gamma subunit provides the primary site of activation of the
      chloroplast enzyme: experiments with a chloroplast-like Synechocystis 6803
      mutant.
AB  - The activation characteristics of the F1Fo-ATP synthase (where F1 and Fo are the
      hydrophilic and membrane-bound parts respectively of the enzyme) from
      Synechocystis 6803 wild-type and a Synechocystis 6803 mutant with a chloroplast
      like insertion in the gamma subunit have been studied. Activation of the ATP
      synthase in wild-type and mutant membrane vesicles was performed by acid-base
      transition-induced generation of a proton motive force (Delta mu H+). Since the
      mutant containing the regulatory segment of the chloroplast gamma subunit showed
      thiol-modulation (typical of the chloroplast enzyme), this segment is indeed
      involved in the regulation of enzyme activation. It is shown that the ATP
      synthase from Synechocystis 6803 wild type corresponds functionally to the
      reduced form of the chloroplast ATP synthase, in view of the low Delta mu H+
      required for activation of the enzyme and the high stability of the active state.
      Both the cyanobacterial wild-type and mutant ATP synthases can be activated by
      methanol, which apparently does not require the presence of the gamma subunit
      regulatory segment.

PMID- 9169621
TI  - Assignment of a single disulphide bridge in human alpha2-antiplasmin:
      implications for the structural and functional properties.
AB  - Human alpha2-antiplasmin (alpha2AP) is a serpin involved in the regulation of
      blood coagulation. Most serpins, unlike smaller serine proteinase inhibitors, do
      not contain disulphide bridges. alpha2AP is an exception from this generalization
      and has previously been shown to contain four Cys residues organized into two
      disulphide bridges [Lijnen, Holmes, van Hoef, Wiman, Rodriguez and Collen (1987)
      Eur. J. Biochem. 166, 565-574]. However, we found that alpha2AP incorporates
      iodo[14C]acetic acid, suggesting that the protein contains reactive thiol groups.
      This observation prompted a re-examination of the state of the thiol groups,
      which revealed (i) a disulphide bridge between Cys43 and Cys116, (ii) that Cys76
      is bound to a cysteinyl-glycine dipeptide, and (iii) and Cys125 exists as either
      a free thiol or in a mixed disulphide with another Cys residue. The disulphide
      identified between Cys43 and Cys116 appears to be conserved in orthologous
      proteins since the homologous Cys residues form disulphide bonds in bovine and
      possibly mouse alpha2AP. The conservation of this disulphide bridge suggests that
      it is important for functional aspects of alpha2AP. However, the structural and
      functional analysis described in this study does not support this conclusion.

PMID- 9169622
TI  - Transformation of subcutaneous nitric oxide into nitrate in the rat.
AB  - Following its addition to arterialized blood in vitro, nitric oxide (NO) is
      transformed into nitrate in the erythrocytes. Inhaled NO is similarly transformed
      into nitrate in the blood in vivo. These observations suggest that nitrate is a
      universal end-metabolite of NO, i.e. of endogenously formed NO as well. However,
      endogenous NO may also be inactivated in tissues, i.e. outside the vascular
      lumen. To study the fate of NO metabolized with delayed access to the blood, rats
      were given subcutaneous injections of 15NO or K15NO3, and the plasma
      concentrations of 15NO3(-) were followed for 450 min after injection. The values
      for the distribution volume and plasma decay (t12) of 15NO3(-) did not differ
      between rats given 15N-labelled NO and NO3(-). The area under the plasma decay
      curve for rats given 15NO amounted to 89% of the corresponding area for animals
      given K15NO3. This demonstrates that 15NO, when given extravascularly in
      millimolar concentrations, is mainly transformed into 15N-labelled nitrate. Other
      rats were kept in an atmosphere containing a mixture of 16O2 and 18O2. Nitrate
      residues containing either one or two 18O atoms were isolated from the blood,
      indicating that inhaled oxygen was incorporated during both the formation of NO
      and the subsequent transformation of NO into nitrate. The fraction of nitrate
      residues containing two 18O atoms was larger than that containing one 18O atom.
      We propose that nitrate is a major stable metabolite of endogenous NO that does
      not primarily diffuse into the vascular lumen following formation. Hence nitrate
      seems to be the quantitatively most important end-product of the metabolism of
      endogenous NO. The transformation of endogenous NO into nitrate involves the
      incorporation of inhaled oxygen.

PMID- 9169623
TI  - A classification of dextran-hydrolysing enzymes based on amino-acid-sequence
      similarities.

PMID- 9169624
TI  - Air pollution, temperature, and regional differences in lung cancer mortality in
      Japan.
AB  - In this study, the authors investigated regional differences in lung cancer
      mortality in Japan, and, based on data acquired between 1970 and 1990 for 47
      Japanese prefectures, estimated the relationship between regional lung cancer
      mortality and air pollution and/or temperature. Investigators used data for
      nitrogen dioxide, sulfur dioxide, motor vehicle density, tobacco expenditure, and
      temperature as independent variables for age-adjusted lung cancer death rates.
      The age-adjusted lung cancer death rates were higher in the southern geographical
      block of Japan (i.e., approximately 1.2-fold in males and 1.1-fold in females)
      and in the northern block (approximately 1.2-fold in males) than in the central
      block. The regional differences in the age-adjusted lung cancer death rates were
      explained by nitrogen dioxide and temperature. Temperature caused a greater
      effect (regression coefficients) of nitrogen dioxide on the age-adjusted lung
      cancer death rates than did nitrogen dioxide alone in the southern block (i.e.,
      approximately 1.3-fold in males and 1.2-fold in females). These results provide
      the first evidence of a possible synergistic interaction between air pollution
      and high temperature on lung cancer mortality.

PMID- 9169625
TI  - Human exposure to elemental mercury in a contaminated residential building.
AB  - Residents of a condominium building in Hoboken, New Jersey, were exposed to
      mercury contamination in indoor air. Elevated levels of mercury were detected in
      urine samples provided by the residents, and 69% of the urine mercury levels were
      20 microg/l or greater. Urine mercury levels were correlated positively with the
      duration of residency in the building and with the time (i.e., h/d) residents
      spent in the building. Environmental and biomonitoring data indicated that the
      residents were being exposed to mercury levels that were cause for health
      concern. Local health authorities, therefore, declared the building to be unfit
      for habitation and ordered that the premises be vacated. Health officials
      monitored the personal belongings of residents for mercury contamination before
      the items were removed from the building. The residents were offered medical
      evaluations and support services as part of the relocation effort.

PMID- 9169626
TI  - Longitudinal distribution of ozone absorption in the lung: effects of nitrogen
      dioxide, sulfur dioxide, and ozone exposures.
AB  - Investigators used an ozone bolus inhalation method to study the effects of
      continuous exposure to ozone, nitrogen dioxide, and sulfur dioxide on ozone
      absorption in the conducting airways of human lungs. Healthy, young nonsmokers (6
      males, 6 females) were exposed on separate days for 2 h to air containing 0.36
      ppm nitrogen dioxide, 0.75 ppm nitrogen dioxide, 0.36 ppm sulfur dioxide, or 0.36
      ppm ozone. Every 30 min, the subject interrupted exposure for approximately 5
      min, during which he or she orally inhaled five ozone boluses-each in a separate
      breath. Investigators targeted penetration of the boluses distal to the lips in
      the 70-130-ml range, which corresponded to the lower conducting airways. The
      authors computed the change in absorption resulting from exposure (delta lambda)
      by comparing the amount of each ozone bolus that was absorbed with a
      corresponding value obtained prior to exposure. Results indicated that ozone
      exposure caused delta lambda to decrease relative to air exposure (p < .01),
      whereas both nitrogen dioxide and sulfur dioxide exposures caused an increase in
      delta lambda that was not significantly different from air exposure. This
      resulted, at least in part, to an artifact caused by preexposure to ozone
      boluses. The authors concluded that exposure of the lower conducting airways to
      nitrogen dioxide or sulfur dioxide increased their capacity to absorb ozone
      because more of the biochemical substrates that are normally oxidized by ozone
      were made available. During continuous ozone exposure, this excess of substrate
      is depleted and the absorption of ozone boluses decreases.

PMID- 9169627
TI  - Chamber exposures of children to mixed ozone, sulfur dioxide, and sulfuric acid.
AB  - To help assess acute health effects of summer air pollution in the eastern United
      States, we simulated ambient "acid summer haze" as closely as was practical in a
      laboratory chamber. We exposed young volunteers who were thought to be sensitive
      to this pollutant mixture on the basis of previous epidemiologic evidence.
      Specifically, we exposed 41 subjects aged 9-12 y to mixed ozone (0.10 ppm),
      sulfur dioxide (0.10 ppm), and 0.6-microm sulfuric acid aerosol (100 +/- 40
      microg/m3, mean +/- standard deviation) for 4 h, during which there was
      intermittent exercise. Fifteen subjects were healthy, and 26 had allergy or mild
      asthma. The entire group responded nonsignificantly (p > .05) to pollution
      exposure (relative to clean air), as determined by spirometry, symptoms, and
      overall discomfort level during exercise. Subjects with allergy/asthma showed a
      positive association (p = .01) between symptoms and acid dose; in healthy
      subjects, that association was negative (p = .08). In these chamber-exposure
      studies, we noted less of an effect than was reported in previous epidemiologic
      studies of children exposed to ambient "acid summer haze."

PMID- 9169628
TI  - Nitrogen dioxide, the oxides of nitrogen, and infants' health symptoms. ALSPAC
      Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
AB  - In this cross-sectional postal study, the authors measured nitrogen dioxide
      levels inside infants' bedrooms and outside their homes. During the 2-wk
      monitoring period, the authors investigated the association between nitrogen
      dioxide levels and 20 infant symptoms. The subjects were 1,200 women who had
      infants aged 3-12 mo. Median levels of indoor and outdoor nitrogen dioxide were
      6.8 and 12.6 ppb, respectively. Environmental factors that were associated
      significantly with indoor levels were gas cooking, cigarette smoking, reported
      traffic levels, and presence of a kerosene heater; use of a cooker hood was
      associated negatively with indoor nitrogen dioxide levels. There was no evidence
      for any short-term significant association between prevalence of respiratory
      symptoms and nitrogen dioxide levels. Diarrhea, the only symptom associated
      significantly and positively with indoor nitrogen dioxide levels, had unadjusted
      and adjusted odds ratios of 1.48 (95% confidence interval: 1.13, 1.95) and 1.38
      (1.11, 1.70), respectively. This association is discussed in terms of a proposed
      mechanism with nitric oxide. No association between a gas cooker in the home and
      diarrhea was found. The association between diarrhea and nitrogen dioxide level
      might have been a chance finding; the authors investigated 20 symptoms, and at
      least 1 was expected to be significant at the .05 level. The finding, however,
      was similar to that reported in a previous study in which a gas cooker was a
      proxy for nitrogen dioxide exposure.

PMID- 9169629
TI  - Sex differences in task performance associated with attention to ambient odor.
AB  - The effects of ambient odor (pleasant, unpleasant, none); odor suggestion
      (present, absent); and sex of subject on mood and performance measures were
      explored in a 3 x 2 x 2 experimental design. A total of 40 men and 40 women
      performed a clerical task and a speed and accuracy task (digit deletion), filled
      out self-evaluations of mood, predicted performance, and rated the odor quality
      of the test room. Ambient odor conditions significantly affected room smell
      ratings, but they had no effect on performance or mood. Odor suggestion produced
      a significant sex-related interaction effect on the digit deletion task,
      irrespective of actual ambient odor. The results are discussed with respect to
      sex differences observed in laboratory studies and in epidemiological
      investigations of multiple chemical sensitivity and sick building syndrome.

PMID- 9169630
TI  - Indoor pollution and sick building syndrome symptoms among workers in day-care
      centers.
AB  - In this study, we investigated indoor air quality and symptoms of respiratory
      illness in 264 nursing workers at 28 day-care centers in Taipei. Geometric mean
      concentrations of indoor and outdoor bacteria were 735 colony-forming units in
      air (CFU/m3) and 384 CFU/m3, respectively. In addition, geometric mean
      concentrations of indoor and outdoor fungi were 1,212 CFU/m3 and 1,032 CFU/m3,
      respectively. Aspergillus, Cladosporium, and Penicillium-microfungi that occurred
      most commonly-were found indoors and outdoors. Geometric mean concentrations of
      house dust mite allergens, Der p I and Der p V, were 58 ng/g dust and 14 ng/g
      dust, respectively. In addition, the observed high prevalence of dampness or mold
      problems in the day-care centers indicated that dampness was very common in this
      subtropical region. We found a significant relationship between dampness and work
      related sick building syndrome in the day-care-center workers. Furthermore,
      concentrations of fungi were lower in the day-care centers equipped with air
      conditioners/air cleaners than in centers that lacked such equipment. Also,
      Aspergillus was associated strongly with work-related sick building syndrome in
      the day-care-center workers.

PMID- 9169631
TI  - House dust mite allergens (Der p I and Der p V) within domestic environments of
      atopic and control children.
AB  - We used allergen-specific ELISA to evaluate environmental distributions of house
      dust mite allergens (Der p I and Der p V) in the homes of 46 asthmatic, 20
      atopic, and 26 nonatopic control children during the summer and winter. Geometric
      mean Der p I levels were approximately 10 times higher than geometric mean Der p
      V concentrations. The concentrations of Der p I and Der p V in winter were
      significantly higher than concentrations found in summer. In addition, we found
      no differences in Der p I concentrations among the three groups in summer;
      however, in winter, Der p I levels in the control group were significantly higher
      than levels in the homes of both asthmatic and atopic children. During the
      summer, concentrations of Der p V were lower in the control group, compared with
      the asthmatic group, but during the winter, concentrations in the control group
      were higher than levels found in either asthmatic or atopic children's homes. In
      this study, we did not establish an important relationship between mite allergen
      exposure and atopy/asthma.

PMID- 9169632
TI  - Exposure to chromium dust from homes in a Chromium Surveillance Project.
AB  - Investigators used a Lioy-Weisel-Wainman sampler to analyze the chromium content
      in house-dust samples obtained from households near chromium waste sites in
      Hudson County, New Jersey. Chromium concentrations in dust (microg/g)-indicative
      of non-background source contributions-were significantly higher in Jersey City
      homes than in control homes outside of Hudson County (228 and 111 microg/g,
      respectively; p < .001). Chromium dust loadings on surfaces (ng/cm2),
      representing the amount of chromium available for contact and a direct measure of
      exposure potential, were also higher in Jersey City homes than in control homes
      (31 ng/cm2 and 14 ng/cm2, respectively; p = .008). Near some of the sites,
      investigators found elevated chromium dust loads more frequently in homes
      occupied by at least one household member who had elevated urine chromium, as
      determined in a separate screening project, than in homes occupied by members
      whose urine chromium was not elevated. Individuals with elevated urine chromium
      levels were found less frequently in homes in which good housekeeping practices
      were evident than in homes absent such practices.

PMID- 9169633
TI  - An assessment of the tumorigenic properties of a Hudson County soil sample
      heavily contaminated with hexavalent chromium.
AB  - During much of this century, Hudson County, New Jersey, was a major center for
      the processing of chromium ore. Some of the residue from this processing was used
      in landfills and in construction materials throughout the county and, in some
      cases, in highly populated areas. Given that it is widely accepted that exposure
      to hexavalent chromium compounds poses a risk for the development of respiratory
      tract cancer, concerns were raised that individuals who worked or resided in
      chromium-contaminated areas might be at increased risk for the development of
      respiratory cancer. To address these concerns, we evaluated a Hudson County soil
      sample-heavily contaminated with chromium ore residue (Cr(+6) concentration at 5
      895 mg/kg)-with respect to its carcinogenic potential to the respiratory tract of
      Sprague-Dawley rats. Groups of animals were given repeated intratracheal
      exposures to one of four materials: (1) Hudson County chromium-contaminated soil
      (CCS), (2) CCS augmented with calcium chromate (CaCrO4), (3) CaCrO4 alone, or (4)
      control soil. Nominal total doses of Cr(+6) for each respective group were 324
      microg/kg, 7,975 microg/kg, 8,700 microg/kg, and 0.02 microg/kg. Incidences of
      malignant tumors and nephritis were not elevated in any group. Four primary lung
      tumors appeared in animals that received CCS + CaCrO4, and one primary lung tumor
      appeared in the group treated with CaCrO4 alone. These incidences were not
      significant statistically, but the rare spontaneous occurrence of these tumors in
      Sprague-Dawley rats suggested that they were treatment related. No primary lung
      tumors appeared in the control or CCS-treated groups.

PMID- 9169634
TI  - Magnetic field exposures in an automobile transmission plant.
AB  - Inconsistent findings from recent mortality studies of workers exposed to
      magnetic fields have led to calls for more detailed understanding of exposure
      distributions and metrics in various industries. The authors undertook personal
      monitoring at an automobile transmission plant to (a) learn if magnetic field
      exposure differences were present, (b) make assignments for a brain cancer study,
      and (c) compare two exposure indices. A wide range of average exposures occurred
      (i.e., 0.016-4.6 microtesla). Within-day variability was also large, and it
      reached 4 orders of magnitude for some workers. Unexpectedly, demagnetizers were
      found among the strong sources that contributed to elevated exposures. The
      authors used conventional summary measures to assign job groups to exposure
      categories, and they used a new index of exposure irregularity to make
      alternative assignments. These new assignments appeared to differ from the
      original ones with respect to work time in each exposure group (i.e., 54% of the
      work time fell into different exposure categories).

PMID- 9169635
TI  - Alcohol consumption and smoking habits as determinants of blood lead levels in a
      national population sample from Germany.
AB  - We investigated the influence of various lifestyle factors on blood lead levels
      in a representative sample from the general adult population (i.e., > or = 18 y
      of age) of West Germany in 1987-1988. The overall mean blood lead level was 73
      microg/l (standard deviation = 41.4 microg/l) in 834 men and 54 microg/l
      (standard deviation = 26.8 microg/l) in 1,065 women. In a multiple linear
      regression analysis, alcohol consumption accounted for the largest proportion of
      variability in blood lead levels, followed by both age and smoking. Other
      significant contributing factors were gender, hematocrit, calcium intake, and
      consumption of milk and milk products. Wine had a greater effect on blood lead
      levels than beer (i.e., per g of alcohol consumed). With respect to cigarette
      smoking (i.e., no. of cigarettes smoked/d), filterless cigarettes were associated
      with higher blood lead levels than filter-tipped cigarettes. In addition, smoking
      cigars, cigarillos, or a pipe resulted in higher blood lead levels than smoking
      only cigarettes. Alcohol consumption and smoking were independent contributors to
      blood lead levels in both men and women, but effects of alcohol consumption were
      stronger in women than in men. We concluded that consumption of alcohol and
      tobacco represent major avoidable sources of lead exposure.

PMID- 9169636
TI  - Exposure of pharmacy technicians to antineoplastic agents: reevaluation after
      additional protective measures.
AB  - In the past, special guidelines and protective measures have been introduced to
      protect hospital workers during the handling of antineoplastic agents;
      nevertheless, it was found that they did not prevent the uptake of these toxic
      compounds. In response, additional protective measures were introduced, including
      adaptations of the laminar downflow hood, use of special masks, use of double
      pairs of gloves, and replacement of ampules with vials. In the current study, the
      authors compared the effects in these additional measures with results of a
      previous study. Cyclophosphamide, 5-fluorouracil, and methotrexate constituted
      81% of the antineoplastic agents prepared; therefore, the investigators monitored
      these compounds again by personal air sampling and by determining the levels of
      contamination on masks and gloves. Cyclophosphamide in the urine of workers was
      also measured. During preparation, investigators concluded that there were lower
      concentrations of cyclophosphamide in the air than had occurred in the previous
      study. Replacement of ampules with vials (i.e., 5-fluorouracil) resulted in a
      significantly diminished contamination of latex gloves. Cyclophosphamide was
      detected in urine samples provided by six of nine technicians; the maximum amount
      excreted over 5 d was 2.6 microg. The mean cyclophosphamide excretion/d was not
      significantly lower than that found in the previous study (0.16 microg and 1.44
      microg, respectively). Despite an intensified hygienic regimen, exposure to
      antineoplastic agents cannot be reduced if the reasons for exposure remain
      unknown.

PMID- 9169637
TI  - Paranoid psychosis after exposure to cyanide.

PMID- 9169638
TI  - A Consensus Statement on unrelated donor bone marrow transplantation from the
      Consensus Panel chaired by EC Gordon-Smith.

PMID- 9169639
TI  - Donor search or autografting in patients with acute leukaemia who lack an HLA
      identical sibling? A matched-pair analysis. Acute Leukaemia Working Party of the
      European Cooperative Group for Blood and Marrow Transplantation (EBMT) and the
      International Marrow Unrelated Search and Transplant (IMUST) Study.
AB  - One hundred and ninety-one patients with acute leukaemia who received bone marrow
      from HLA-A, -B and -DR identical unrelated donors and were reported to EBMT
      and/or IMUST, were matched with 382 patients receiving autologous bone marrow for
      diagnosis, age, stage of disease and year of transplantation. Transplant-related
      mortality (TRM) was significantly higher in recipients of unrelated marrow
      compared to autograft recipients, 44 +/- 4% (+/- 95% confidence interval) and 15
      +/- 3% at 2 years in the two groups, respectively (P < 10(-4)). In contrast,
      relapse probability was lower in recipients of unrelated marrow, being 32 +/- 5%
      at 2 years compared to 55 +/- 3% in recipients of autografts (P < 10(-4)). Two
      year leukaemia-free survival (LFS) in patients with acute lymphoblastic leukaemia
      was 39 +/- 5% and 32 +/- 3% in the two groups, respectively. Among patients with
      acute myeloid leukaemia (AML), the corresponding figures were 36 +/- 6% and 46 +/
      5% in the two groups, respectively (P = NS). In AML in first remission (CR-1),
      the 2-year survival was 42 +/- 10% in recipients of unrelated bone marrow,
      compared to 69 +/- 8% in autograft recipients (P = 0.008). When all patients with
      acute leukaemia were included, the 2-year LFS was 38% in recipients of unrelated
      marrow, compared to 37% in autograft recipients (NS). In conclusion, this
      retrospective analysis supports the design of a prospective randomized study in
      patients with high-risk/advanced acute leukaemia who lack a suitable related bone
      marrow donor, to ascertain which of the two strategies, if any, should be
      favoured.

PMID- 9169640
TI  - Autografting in Philadelphia (Ph)+ chronic myeloid leukaemia using cultured
      marrow: an update of a pilot study.
AB  - Incubation of CML marrow in long-term culture (LTC) conditions may result in
      selection of normal (Ph-) LTC-initiating cells (LTC-IC) as early as 10 days, and
      in production of Ph- clonogenic cells and mature end cells within 5 weeks. This
      was the rationale for using marrow cells from 10-day-old LTC to autograft nine
      chronic phase CML patients, ineligible for HLA-matched sibling donor transplant,
      and who were selected on the basis of a pre-transplant screening LTC test. Of the
      transplanted patients three died; two of graft failure and one of therapy-related
      toxicity with 97% Ph- cells 16 months following the autograft. The reconstituting
      haemopoietic cells in the seven engrafted patients were 100% Ph- in four, > or =
      90% Ph- in two and 71% Ph- in the seventh, with a duration of complete
      cytogenetic response of 6-12 months. Three patients reverted to chronic phase and
      100% Ph+ haemopoiesis 27-36 months post-autograft. The other three patients
      remain in continuous haematological remission with 22% Ph- cells in one and
      complete cytogenetic remission in the other two 3-4 years post-autograft. IFN
      therapy was generally introduced on the first evidence of recurrence of Ph+ cells
      or of cytogenetic deterioration. Further strategies to modulate immune
      surveillance in vivo may improve the outcome of cultured marrow autografts which
      give an initial and rather prolonged bias towards Ph- haemopoiesis.

PMID- 9169641
TI  - Management of lymphoma recurrence after allogeneic transplantation: the relevance
      of graft-versus-lymphoma effect.
AB  - Donor lymphocyte infusions, by virtue of a graft-versus-tumor effect, have been
      shown to induce remissions in leukemia that recurs after allogeneic bone marrow
      transplantation. Similar effects have been postulated to contribute to the
      decreased recurrence rate observed after allogeneic transplantation in non
      Hodgkin's lymphoma. This lower recurrence rate may be due to a variety of other
      mechanisms. We aimed to evaluate the role of graft-versus-lymphoma effects in
      patients in whom lymphomas recur after allogeneic transplantation. At the time of
      recurrence, immunosuppressive therapy was withheld. Patients with non-responding
      disease received an infusion of donor lymphocytes. Patients were observed for
      response and graft-versus-host disease. Disease in four of nine patients
      responded to withdrawal of immunosuppressive therapy. A minor response was
      observed in one of three recipients of donor lymphocyte infusions. Responses were
      observed among two patients with follicular lymphoma, one with large cell
      lymphoma and one with lymphoblastic lymphoma. A minor response was observed in a
      patient with prolymphocytic leukemia/lymphoma. We conclude that withdrawal of
      immunosuppressive therapy and donor lymphocyte infusion can induce durable
      remissions in patients with recurrent lymphoma after allogeneic transplantation.

PMID- 9169642
TI  - A novel high-dose chemotherapy protocol with autologous hematopoietic rescue in
      patients with metastatic breast cancer or recurrent non-Hodgkin's lymphoma.
AB  - In this phase II trial, we used a double dose-intensive chemotherapy and stem
      cell rescue protocol to treat breast cancer (BCA) patients or non-Hodgkin's
      lymphoma patients (NHL). The first cycle consisted of high-dose melphalan
      followed by ABMT. The second cycle used a novel chemotherapy combination;
      thiotepa, etoposide, carboplatin and cyclophosphamide (TECC) followed by ABMT. We
      treated 12 patients in total, nine with BCA, three with NHL. All nine BCA
      patients were treated with the two cycle protocol. The three NHL patients were
      treated with the second cycle only. Bone marrow (BM, 1 patient), peripheral blood
      stem cells (PBSC, 10 patients) or both (1 patient) were reinfused 60-72 h after
      completion of each cycle of chemotherapy. Recovery was rapid; the ANC rose to
      greater than 500/microl on day +11 (+8 to + 20) and the platelet count to greater
      than 20000/microl on day +12 (+6 to +20). The toxicities included the expected
      neutropenic fevers, severe mucositis, diarrhea, and a low incidence of mild renal
      insufficiency. No patients developed veno-occlusive disease, hemorrhagic cystitis
      or overt bleeding. With a mean follow-up of 37 months, 83.3% of the patients are
      alive. Six patients are in complete remission; one patient with BCA relapsed and
      expired; one patient with NHL is in CR now over 18 months after relapse and
      subsequent treatment with interferon; one patient is too early to evaluate.
      Progression-free survival overall is 75%, which is at least equivalent to many
      other recent studies using similar regimens. In addition, we have also found that
      delayed addition of G-CSF during the mobilization of PBSC was feasible and
      resulted in excellent CD34+ cell counts and engraftments, and reduced treatment
      costs. These results indicate that this chemotherapy is effective with good
      remission rates and high progression-free survival rates. It is also well
      tolerated with acceptable toxicities that are manageable. Long-term follow-up of
      a larger cohort of patients will be needed to ascertain the overall efficacy of
      this type of therapy.

PMID- 9169643
TI  - Immune escape from a graft-versus-leukemia effect may play a role in the relapse
      of myeloid leukemias following allogeneic bone marrow transplantation.
AB  - We studied patients relapsing with myeloid leukemias following allogeneic bone
      marrow transplantation (BMT) for evidence of immune escape by clonal evolution of
      the leukemia. Relapsed cells from four out of five patients had a reduced ability
      to stimulate proliferation of lymphocytes from an HLA-mismatched responder. There
      was decreased susceptibility to lysis by CTL in three and reduced susceptibility
      to NK-mediated lysis in one. Relapsed leukemias had marked alterations in
      expression of critical surface molecules involved in immune responsiveness. Three
      had decreased expression of MHC class I and II, with no change or increase in
      CD54 (ICAM-1) or CD80 (B7.1). None of these responded to treatment with donor
      lymphocytes. Three patients showed no change, or increased expression of MHC with
      no change or decrease in ICAM-1 or B7.1. Two achieved remission - one in response
      to donor lymphocytes and one following withdrawal of cyclosporine. In one patient
      transplanted with myelodysplastic syndrome in transformation, interferon-gamma
      upregulated expression of MHC molecules in relapsed cells and increased their
      stimulatory capacity and target susceptibility to unmatched responder
      lymphocytes. These results suggest that immune escape through clonal evolution of
      the leukemia is a common occurrence in patients who relapse with myelogenous
      leukemias after BMT.

PMID- 9169644
TI  - Association of donor-derived host-reactive cytolytic and helper T cells with
      outcome following alternative donor T cell-depleted bone marrow transplantation.
AB  - Recipients of marrow from alternative donors (unrelated or HLA-mismatched related
      donors) have a higher incidence of post-transplant complications compared to
      recipients of marrow from HLA-identical siblings. HLA disparity undetected by
      routine typing techniques has been suggested as one cause for the increased
      complications observed. Limiting dilution analysis (LDA) of donor-derived, host
      reactive T cell precursor frequency prior to transplant has been proposed as a
      surrogate indicator of underlying HLA disparity which might be used to predict
      transplant outcome and aid in donor selection. We compared results of LDA of host
      reactive IL-2 producing helper T lymphocytes (HTLp) and/or cytolytic T
      lymphocytes (CTLp) in 77 alternative marrow donor/recipient pairs with transplant
      outcome using univariate and multivariate analysis. All donor grafts were
      depleted ex vivo of mature T cells. Median patient age was 15 years (1-53). Donor
      selection was based on serologic typing for HLA class I and high resolution
      oligotyping for HLA-DRB1-DRB5, and HLA-DQB1. HLA-A and HLA-B locus antigens were
      retrospectively defined by one dimensional isoelectric focusing (IEF). Cox
      proportional hazards regression models were used to assess the impact of
      frequency and estimated cell dose of CTLp and HTLp on outcome. The CTLp assay was
      most sensitive to HLA-A and HLA-B locus disparity detected by serology or IEF.
      The HTLp assay detected class I disparity but was most strongly reactive in the
      presence of HLA-DRB1 disparity. Univariate analysis indicated a significant
      association of CTLp frequency and dose with severe (grades 3-4) acute graft
      versus-host disease (GVHD), and of CTLp dose with chronic GVHD. Both assays were
      associated with survival and neither assay was associated with relapse. After
      adjustment for other significant covariables including known HLA disparity, the
      association of CTLp with acute GVHD was lost, however, CTLp frequency and CTLp
      dose remained associated with survival and HTLp frequency was associated with
      chronic GVHD. These data support the hypothesis that post-BMT complications may
      be influenced not only by T cell dose but by the alloreactive potential of the
      cells infused. LDA of alloreactive potential was useful in detecting disparity
      and in predicting survival or chronic GVHD in recipients of alternative donor TCD
      marrow grafts.

PMID- 9169645
TI  - Deficient reconstitution of early progenitors after allogeneic bone marrow
      transplantation.
AB  - Allogeneic bone marrow transplant recipients maintain normal peripheral blood
      counts long term, suggesting durable support from engrafted stem cells. In order
      to investigate late hemopoietic reconstitution at the level of committed and
      early progenitors (LTC-IC), we studied 64 long-term survivors at a median
      interval of 6 years (range: 2-20) after allogeneic bone marrow transplant. CFU-GM
      and BFU-E numbers did not differ from normal controls; CFU-GEMM were found to be
      significantly decreased (1.2 +/- 0.2/10(5) vs 3.1 +/- 0.4, P = 0.001). The most
      remarkable defect was however, the low frequency of LTC-IC (3.2 +/- 0.6/10(6) vs
      54.2 +/- 9.3, P = 0.0001) that did not improve with time and did not correlate
      with phase of the disease, conditioning regimen, CMV infections or GVHD. Number
      of infused cells and CFU-GM content of marrow grafts did not seem to influence
      the number of LTC-IC. This study documents a significantly reduced number of
      early progenitors in BMT patients despite normal numbers of committed progenitors
      and normal peripheral blood counts. This finding may suggest a permanent
      reduction of the stem cell reservoir after allogeneic bone marrow
      transplantation.

PMID- 9169646
TI  - Abnormal thyroid stimulating hormone (TSH) levels in adults following allogeneic
      bone marrow transplants.
AB  - Thyroid function abnormalities in 270 adult patients post-BMT are described.
      Various conditioning regimens were used and the effects of three TBI and one
      chemotherapy only based regimens are compared. The overall incidence of elevated
      TSH is 8.9; 3.8, 7.2 and 16.7% in those patients who received 300, 500 and 1200
      cGy respectively and 11.7% in those who received BuCy conditioning. Three cases
      (1.1%) of clinial hypothyroidism were observed. Compensated hypothyroidism
      defined as an elevated TSH in the presence of normal T3, T4 levels and transient
      in some cases, was the most common finding. All but four cases occurred in the
      first 2 years after BMT. In the remaining four, three occurred in patients with
      chronic GVHD. The results reported here show a lower prevalence than observed in
      most other reviews, particularly for children. A trend was observed with
      increasing radiation doses. The results are not significantly different from
      those we observed in the BuCy regimen.

PMID- 9169647
TI  - Umbilical cord blood collection and separation for haematopoietic progenitor cell
      banking.
AB  - Cord blood transplantation has been proven to be a suitable form of treatment for
      a variety of diseases in childhood and more recently in an increasing number of
      adult patients. Banks of cord blood cryopreserved after HLA testing are required
      in order to provide various HLA types for unrelated transplantation. To optimize
      storage space cord blood needs to be stored as a separated product. Several early
      methods of cord blood separation resulted in a significant loss of progenitor
      cells. We used a separation procedure where the donation was separated by
      centrifugation into a buffy coat fraction, a red cell fraction, and a plasma
      fraction. Twenty-five samples, (mean initial volume 81 ml) were assessed.
      Nucleated cells were recovered in the buffy coat fraction. Recoveries of
      nucleated cell count, total progenitors and CD34-positive cells in the buffy coat
      were 90%, 88% and 100%, respectively. The buffy fraction was tested for sterility
      by aerobic and anaerobic culture. Using this closed bag system, volume reduction
      was achieved while maintaining sterility and retaining progenitor cells in a
      final mean buffy coat volume of 44 ml. Red cell and plasma fractions were
      available for ABO grouping, virology testing and cryopreservation. The results
      show that cord blood can be effectively volume-reduced using simple and readily
      available blood banking techniques.

PMID- 9169648
TI  - Suppression of progenitor cell growth by vancomycin following autologous stem
      cell transplantation.
AB  - The occurrence of hematologic side-effects resulting from the use of vancomycin
      is rare. Prior to this report, vancomycin-induced neutropenia was believed to be
      due to a hypersensitivity reaction since antibodies directed against circulating
      neutrophils have been discovered in the serum of some patients. We demonstrate
      suppression of hematopoietic bone marrow progenitor cells in a patient
      experiencing vancomycin-induced neutropenia after an autologous hematopoietic
      stem cell transplantation for multiple myeloma. A bone marrow (BM) specimen
      obtained at the time of neutropenia demonstrated direct suppression of progenitor
      cell growth in vitro when vancomycin was added at increasing concentrations (1,
      10 and 50 microg/ml). No such trend was noted in a BM sample from the same
      patient obtained 11 months prior to transplantation and a normal control BM. The
      decrease in the total number of colony-forming units (CFU) was statistically
      significant at all the dose levels of vancomycin when compared to the number of
      CFU in the baseline BM sample (P < 0.05). The myeloid maturation arrest observed
      in the bone marrow sample obtained during the period of neutropenia and the dose
      dependent growth inhibition by vancomycin observed in vitro suggest a novel
      nonimmune mechanism of hematologic effects due to suppression of bone marrow
      progenitor cell growth.

PMID- 9169649
TI  - The use of an expanded circulating hematopoietic progenitor cell pool associated
      with bone marrow fibrosis for the support of autologous transplantation in IgD
      multiple myeloma.
AB  - Leukoerythroblastosis and myelofibrosis were observed at presentation in a
      patient with IgD myeloma. Interestingly, a 1000-fold increase in peripheral blood
      progenitor cells (PBPC) was found in the steady state without signs of any
      underlying myeloproliferative disorder. The myeloma was resistant to conventional
      therapy. The expanded PBPC were collected in the steady state and used to support
      two consecutive myeloablative courses. A complete remission of the myeloma was
      achieved, with resolution of myelofibrosis. Furthermore, the unprimed PBPC
      expanded as a result of myelofibrosis, provided a sustained hematopoietic
      reconstitution. This indicated that their hematopoietic potential was equivalent
      to that of PBPC mobilized by chemotherapy or growth factors.

PMID- 9169650
TI  - Autologous peripheral blood progenitor cell transplantation for non-Hodgkin's
      lymphoma with extensive bone marrow necrosis.
AB  - A patient with malignant lymphoma, large cell type and extensive bone marrow
      necrosis at presentation is reported. Bone marrow necrosis persisted even after a
      complete remission was induced with standard chemotherapy. Because of this
      adverse prognostic factor, circulating stem cells were collected and reinfused
      following a myeloablative regimen consisting of busulfan, etoposide and
      cyclophosphamide. The patient engrafted rapidly and a subsequent bone marrow
      examination was free of both lymphoma and necrosis. To the best of our knowledge,
      this is the first reported patient with extensive bone marrow necrosis in whom
      circulating progenitor cells were harvested and utilized successfully.

PMID- 9169651
TI  - Transfer of autoimmune thyroiditis and resolution of palmoplantar pustular
      psoriasis following allogeneic bone marrow transplantation.
AB  - We report an unusual case of a patient who was cured of one autoimmune disease
      (palmoplantar pustular psoriasis (PPP)) but developed another autoimmune disease
      (autoimmune thyroiditis) after allogeneic BMT. A 40-year-old man suffering from
      AML with PPP underwent allogeneic BMT from his HLA-identical sister for the
      treatment of AML. The patient experienced complete clearance of the cutaneous PPP
      despite the cessation of immunosuppressive therapy for over 2 years. However, he
      developed hyperthyroidism with anti-thyroglobulin antibodies 5 months after BMT,
      although he had showed normal thyroid functions without anti-thyroglobulin
      antibodies before BMT. The donor had no history of thyroid diseases and showed
      normal thyroid functions but was positive for anti-thyroglobulin antibodies.
      Thus, even when the donor is in a subclinical state, autoimmune thyroiditis may
      be transferred from donors to recipients by BMT.

PMID- 9169652
TI  - Hemolytic uremic syndrome following autologous peripheral blood stem cell
      transplantation in a patient with malignant lymphoma.
AB  - Hemolytic uremic syndrome (HUS) has been reported in patients receiving bone
      marrow transplantation. However, only a few cases of HUS following autologous
      peripheral blood stem cell transplantation (PBSCT) have been reported. We present
      a case of HUS developing after autologous PBSCT in a 40-year-old man with non
      Hodgkin's lymphoma. It appears that the chemotherapeutic agents administered
      during the conditioning regimen for PBSCT may have played an important role in
      the development of HUS in our patient. In the present case, the combination
      therapy of vincristine, methylprednisolone, and ticlopidine hydrochloride was
      effective.

PMID- 9169653
TI  - Reversible brain MRI changes in acyclovir neurotoxicity.
AB  - This case report shows reversible brain MRI changes probably associated with
      acyclovir toxicity. So far, neuroimaging in acyclovir toxicity had been negative
      or uninformative. A 12-year-old girl developed focal secondary generalizing
      epileptic fits following 4 weeks of prophylactic administration of acyclovir (3 x
      10 mg/kg body weight/day i.v.) on day +22 after allogeneic peripheral blood stem
      cell transplantation for CML. Infective causes were excluded. Brain MRI
      demonstrated multiple gadolinium-enhancing areas with impairment of the blood
      brain barrier in cortical and subcortical regions. Clinical symptoms and
      neuroimaging pathology resolved completely within 9 days of acyclovir withdrawal.

PMID- 9169654
TI  - Detection of hepatitis G virus from serum and liver of a patient with long-term
      liver dysfunction after autologous bone marrow transplantation.
AB  - Long-term effects after blood or bone marrow transplantation (BMT) are emerging
      as an important issue, as more patients are included in BMT programmes and as
      this procedure becomes more successful. Long-term liver dysfunction, mainly due
      to chronic graft-versus-host disease or hepatitis C virus infection, is a well
      known complication. Nevertheless, the diagnosis of liver disease in this patient
      group is sometimes difficult and, despite adequate studies, it may remain
      undetected. A novel hepatitis-associated virus, hepatitis G virus (HGV), has
      recently been identified. The virus belongs to the Flaviviridae family and is
      known to be parenterally transmitted, although there is no clear evidence to
      implicate this agent in causing acute or chronic hepatitis. We report a patient
      who developed mild, but persistent, abnormalities in transaminases for 2 years
      after an autologous BMT. HGV RNA was detected in both serum and liver. HGV RNA
      persisted in serum for at least 8 months. No other known hepatitis virus was
      found. This report provides the first direct evidence of a patient with long-term
      liver abnormalities after a BMT in whom the only known hepatitis virus isolated
      was the HGV.

PMID- 9169655
TI  - Bone marrow transplantation for Epstein-Barr virus-related clonal T cell
      proliferation associated with hemophagocytosis.

PMID- 9169656
TI  - Leukemic vasculitis: a newly described pattern of cutaneous involvement.

PMID- 9169657
TI  - The ASCP Resident Physician Section: results of surveys pertaining to graduated
      responsibility for residents in anatomic pathology. American Society of
      Cytopathology.

PMID- 9169658
TI  - The ASCP Resident Physician Section: results of surveys pertaining to "graduated
      responsibility for residents in anatomic pathology". American Society of
      Cytopathology.
AB  - Graduated responsibility for residents in anatomic pathology has been the subject
      of discussion among supervising staff and residents during the past few years.
      Presently a wide variation exists within pathology residency programs in the
      United States both in the degree of autonomy given to residents and in the areas
      of anatomic pathology (ie, surgical pathology, cytopathology, and autopsy
      pathology) within which the autonomy is granted. Recent surveys of supervising
      staff and residents have indicated a willingness to increase the level of
      independence for residents, especially at senior levels. Impediments include
      reimbursement, credentialing, and medicolegal issues. The results of the ASCP
      Resident Physician Section (RPS) surveys pertaining to graduated responsibility
      for residents in anatomic pathology are discussed.

PMID- 9169659
TI  - Leukemic vasculitis: a feature of leukemia cutis in some patients.
AB  - Cutaneous involvement is common in certain subtypes of acute leukemia and may be
      a reflection of a capacity of these tumors for tissue infiltration. We have
      recently noted that leukemia cutis can be accompanied by vasculitis in a subset
      of patients. We describe six cases of such leukemic vasculitis with findings
      ranging from mild microvascular injury to necrotizing arteritis. All cases were
      seen in patients with acute leukemia with myelomonocytic or monocytic features.
      In one patient, cutaneous leukemic vasculitis represented the initial
      manifestation of leukemia. In most cases, leukemic infiltration of the dermal
      blood vessels was the predominant pattern of involvement with minimal dermal
      infiltration. Vascular injury seemed to be mediated by leukemic blasts and not by
      reactive inflammatory cells. We propose the term leukemic vasculitis to describe
      such lesions.

PMID- 9169660
TI  - The significance of light chain-restricted bone marrow plasma cells after
      peripheral blood stem cell transplantation for multiple myeloma.
AB  - While plasmacytosis is a common occurrence in early post-bone marrow
      transplantation biopsy specimens, the significance of plasma cells in such
      specimens from patients with multiple myeloma (MM) is unknown. We attempted to
      retrospectively determine, by morphologic assessment of plasma cell percentage,
      immunohistologic assessment of plasma cell light chain ratio (LCR), and
      correlation with clinical outcome, the prevalence and significance of
      plasmacytosis in the posttransplantation bone marrow biopsy specimens of 25
      patients with MM who underwent autologous peripheral blood stem cell
      transplantation (PBSCT). No pre-PBSCT morphologic or immunologic characteristics
      were significantly associated with the post-PBSCT outcome in this group of
      patients. While 9% of all biopsy specimens and 25% of hypocellular biopsy
      specimens obtained during the first 60 days after the PBSCT contained more than
      10% plasma cells, 34% of all biopsy specimens obtained during this period had
      elevated LCRs. The dominant light chain in all cases with high LCRs was the same
      as that of the original tumors, implying that these plasma cells represent a
      portion of the patients' original tumors. However, the presence of tumoral plasma
      cells during the early post-PBSCT period was not associated with outcome (P>.5 at
      30 days and 60 days after transplantation). Histologic features of recurrent MM
      and elevated LCR occurring at day 90 or later are correlated with progression of
      disease (P=.02 and P=.0001, respectively). We conclude that the presence of
      tumoral plasma cells in the early post-PBSCT period likely represents residual
      tumor and should not be regarded as indicating imminent relapse, while the
      presence of tumor as assessed by histologic or immunohistochemical evaluation
      during the late post-PBSCT period should raise the concern of relapse and disease
      progression.

PMID- 9169661
TI  - Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and
      myelodysplastic and myeloproliferative syndromes.
AB  - The CD56 antigen is normally expressed on natural-killer cells but has
      additionally been shown to be present on a variety of hematologic malignancies,
      including a subset of acute myelogenous leukemia (AML). There is disagreement,
      however, about its prognostic significance and its association with specific
      cytogenetic abnormalities. All clinical samples from June 1994, through September
      1995, with increased myeloblasts were analyzed by multiparameter flow cytometry
      for anomalous expression of CD56. Patients with CD56+ blast cells were selected,
      and morphologic review was performed. Clinical information was obtained, and
      cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of
      the mixed lineage leukemia (MLL) gene was performed when possible. The samples
      from 23 of 114 patients studied demonstrated anomalous expression of CD56 on
      myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and
      chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients
      with CD56+ AML demonstrated at least partial monocytic differentiation.
      Dysplastic features were displayed in the samples of 12 patients. Correlation
      with specific cytogenetic abnormalities was not found. The MLL gene was
      rearranged in five of 18 patients. Seventeen patients have died, with a median
      survival of 4.6 months for patients with AML. Three have sustained a complete
      remission. One has findings of high-grade myelodysplastic syndrome. Two were
      unavailable for follow-up. Expression of CD56 was found in 20% of patients with
      increased myeloblasts, including patients with high-grade MDS, chronic
      myelogenous leukemia in blast crisis, and AML. This phenotype was associated with
      dysplasia, monocytic differentiation, and rearrangement of the MLL gene.

PMID- 9169662
TI  - CD16 antigen density on neutrophils in chronic myeloproliferative disorders.
AB  - Using flow cytometry, we quantitatively examined the density of the CD16 (IgG Fc
      receptor III) antigen on neutrophils in healthy control subjects, in patients
      with neutrophilia due to bacterial infection, and in patients with chronic
      myeloproliferative disorders (chronic myeloid leukemia [CML], polycythemia vera,
      or essential thrombocythemia). The density was expressed as the mean fluorescence
      intensity of neutrophils stained with fluorescein isothiocyanate-labeled anti
      CD16 monoclonal antibody. We also determined leukocyte alkaline phosphatase
      activity semiquantitatively in the same population. The mean (+/- SD) density of
      the CD16 antigen on neutrophils in patients with CML (n = 13; 240.4 +/- 134.8)
      was lower (P<.001 ) than in healthy control subjects (n = 25; 656.6 +/- 238.0),
      and the density was also lower than in patients with bacterial infection (n = 15;
      671.5 +/- 288.1), polycythemia vera (n = 7; 552.6 +/- 99.9), or essential
      thrombocythemia (n = 11; 671.5 +/- 411.5). The density of the CD16 antigen was
      300 or more in all healthy control subjects and in all patients examined, except
      for those with CML. The CD16 antigen density was less than 300 in 10 of the 13
      patients with CML. Leukocyte alkaline phosphatase activity was also low in 10 of
      the 13 patients with CML. These findings indicate that flow cytometric analysis
      of the density of neutrophil CD16 antigen is useful for the differential
      diagnosis of CML from other chronic myeloproliferative disorders.

PMID- 9169663
TI  - Multiple myeloma with hairy cell-like features.
AB  - Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-described disease
      entities with characteristic clinical and pathologic features. We describe two
      patients initially treated for MM in whom atypical clinical and morphologic
      features subsequently developed that raised the possibility of HCL. Although the
      cytologic appearance and immunophenotype were not diagnostic of HCL, these cases
      challenge the criteria used to diagnose MM, HCL, and other recently described
      villous neoplasms.

PMID- 9169665
TI  - Prothrombin time and activated partial thromboplastin time can be performed on
      the first tube.
AB  - The current practice standard for coagulation studies on venous blood specifies
      the use of the second (or subsequent) tube for testing. Unless other tests are
      ordered, the first tube is discarded. This practice, derived from early
      experience using nondisposable materials, gained support from a report based on
      modern phlebotomy methods but inexperienced phlebotomists. For our study, paired
      blood specimens were collected by experienced phlebotomists from 175 outpatients
      whose physicians had ordered coagulation tests. Prothrombin time (PT) and
      activated partial thromboplastin time (APTT) were performed on the first and
      second tubes. Similar values were obtained for PT and APTT. (PT: n = 174; mean =
      15.36 seconds; mean difference = 0.10 seconds; y = 1.02x - 0.28; t = 0.24; P>.81;
      r = 0.995; APTT: n = 160; mean = 38.25 seconds; mean difference = 0.48 seconds; y
      = 1.03x - 0.71; t = 0.25; P=.80; r = 0.993.) For coagulation tests on specimens
      collected by experienced phlebotomists, the first tube yields accurate results
      and need not be discarded.

PMID- 9169664
TI  - Performance of prothrombin-proconvertin time as a monitoring test of oral
      anticoagulation therapy.
AB  - Outcome and anticoagulation intensity was evaluated during 121 patient years of
      oral anticoagulant therapy monitored with the prothrombin-proconvertin clotting
      time (PP, also known as P&P). The PP-based international normalized ratio (INR;
      PP-INR) correlated well with the INR calculated from the prothrombin clotting
      time (PT; r = 0.92), and results were almost identical over a wide range after
      linear conversion (1/INR). When the PP-INR was 4.5 or less, the risk of major
      bleeding was 1 for every 118 treatment years, but it was 1 for every 73 days when
      the INR was 6 or more. The 1/PP-INR correlated better with factor II coagulant
      activity (r = 0.85) than did the 1/PT-INR (r = 0.78). The 1/PP-INR also
      correlated better with the native prothrombin antigen (r = 0.76) than did the
      1/PT-INR (r = 0.68). The PP and PT results correlated better with factor II
      coagulant activity than with native prothrombin antigen. Thus, the PP clotting
      time results can be accurately converted to INR. The results also suggest that
      the PP may have advantages over the PT as an indicator of anticoagulation
      intensity during oral anticoagulation.

PMID- 9169667
TI  - Hepatocytic globules in end-stage hepatic disease: relationship to alpha1
      antitrypsin phenotype.
AB  - Hepatic explant specimens from 171 patients with cirrhosis were examined to
      determine the incidence of periodic acid-Schiff (PAS)-positive diastase-resistant
      globules (PDRGs) in end-stage hepatic disease and whether the globules bear a
      specific relationship to the alpha1-antitrypsin (A1AT) phenotype or to causes of
      hepatic disease other than A1AT deficiency. PAS-positive diastase-resistant
      globules were detected in 17 (10%) of the hepatic explant specimens, and the
      globules in all of these cases were strongly immunoreactive for A1AT. In the 17
      patients with PDRGs, the cirrhosis was attributed preoperatively to A1AT
      deficiency (3 patients), ethanol abuse, viral hepatitis, or both (10 patients),
      cryptogenic cirrhosis (3 patients), and autoimmune hepatitis (1 patient). The
      A1AT isoelectric phenotypes classified according to the protease inhibitor (Pi)
      nomenclature for 16 of these patients were as follows: Pi ZZ (3 patients), Pi SS
      (1 patient), Pi MZ (8 patients), and Pi MM (4 patients). Because PDRGs were seen
      in a variety of A1AT phenotypes, serum electrophoretic analysis, not histologic
      examination, is required for the correct diagnosis of an A1AT abnormality.
      Furthermore, although PDRGs were seen in a variety of hepatic diseases, the
      majority of patients with globules had an undetected A1AT abnormality.
      Accordingly, on identification of hepatocytic PDRGs, the clinician should be
      alerted to the possibility of an unsuspected A1AT abnormality even in the
      presence of other causes of hepatic disease.

PMID- 9169666
TI  - p21(Waf1/Cip1) and p53 protein expression in breast cancer.
AB  - p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]
      interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a
      downstream mediator of p53. In this study, we sought to clarify the clinical
      significance of Waf1 and the relationship between Waf1 and p53 in breast cancer.
      For this purpose, the expressions of Waf1 and p53 were evaluated
      immunohistochemically in a series of 104 patients. Waf1 was expressed in 51 (49%)
      of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two
      proteins was seen in 76 cases (73%); 47 were Waf1-positive and p53-negative, and
      29 were Waf1-negative and p53-positive. A comparison with clinicopathologic
      parameters showed that Waf1 expression correlated with negative lymph nodes
      (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status
      (P<.01). Recurrence-free survival was lower for patients with Waf1-negative
      tumors than for those with Waf1-positive tumors (P<.0001). In multivariate
      analysis, Waf1 expression and low histologic grade (1 or 2) tumors had an
      independent prognostic significance for recurrence-free survival. These results
      suggest that Waf1 is induced mainly by a p53-dependent pathway and could be a
      reliable indicator of recurrence in breast cancer.

PMID- 9169668
TI  - Squamous carcinoma of the nasal vestibule: an analysis of five cases and
      literature review.
AB  - Five examples of squamous carcinoma of the nasal vestibule are reported. Possibly
      because this keratinizing tumor is histopathologically identical to squamous
      cancer in other locations, reports of this tumor in the pathology literature are
      uncommon. The patients were four men and one woman, of whom three men were
      smokers, although there are no consistent published associations with any
      environmental toxins to determine patients at risk. All five patients had
      localized disease treated by combinations of surgery and radiation therapy. Flap
      reconstructions and skin grafting were used in three patients; two patients
      underwent nasal amputations. Three patients also received postoperative
      irradiation. Three patients experienced recurrences from 2 to 13 years after the
      original treatment; there were no deaths related to this tumor. Histologically,
      these are typically ulcerated tumors seldom showing evidence of in situ
      carcinoma. Surgical margins of excision were positive or close in three cases but
      did not influence the chronic course of the disease. No clinical tumor staging
      system is generally accepted, and it seems that the prognosis for localized
      disease is good irrespective of clinical stage. Aggressive features, including
      penetration of cartilage and invasion of overlying skin, may be impressive, but
      do not preclude long-term survival if bulk disease can be surgically removed.

PMID- 9169669
TI  - Estimation of tumor volume in radical prostatectomy specimens in routine clinical
      practice.
AB  - Tumor volume may be an independent prognostic factor in prostatic adenocarcinoma
      but is too difficult, expensive, and time consuming to measure in routine
      clinical practice. We sought to evaluate several simple estimates of tumor volume
      in radical prostatectomy specimens. Specimens from 86 radical prostatectomies
      were completely sectioned, and the true tumor was volume calculated using a
      computer-assisted image analysis technique. True tumor volume was then compared
      with the results of several estimation techniques. True tumor volume ranged from
      0.004 to 9.74 cc (mean, 1.59 cc). The Pearson correlation coefficient of the
      length of the maximum dimension of tumor as measured from the slide with true
      tumor volume had an r2 of 0.688. However, 15 (75%) of 20 tumors less than 0.5 cc
      had a single maximum diameter of less than 10 mm, and only 3 (4%) of 66 tumors
      with volumes greater than 0.5 cc had a maximum diameter of less than 10 mm.
      Fifteen (68%) of 22 tumors with true tumor volumes greater than 2 cc had a
      maximum dimension greater than 20 mm, and only 2 (3%) of 64 tumors with volumes
      less than 2 cc had a maximum dimension greater than 20 mm. Increasing correlation
      with true tumor volume could be obtained from the largest single tumor area (r2 =
      0.749), the sum of the largest dimensions of two separate tumor foci (r2 =
      0.759), and the sum of the two largest areas (r2 = 0.859). For tumors with true
      volumes less than 0.5 cc, only 1 (5%) of 20 cases had a sum of the two largest
      areas greater than 65 mm2, and no tumor larger than 0.5 cc had a sum of less than
      65 mm2. For tumors larger than 2 cc, 19 (86%) of 22 tumors had a sum of the two
      largest areas greater than 250 mm2, and only 1 (2%) of 64 cases with a true tumor
      volume less than 2 cc had an area greater than 250 mm2. We conclude that tumors
      in radical prostatectomy specimens can be stratified by size based on simple
      measurements obtainable during routine pathology practice.

PMID- 9169670
TI  - Microglandular carcinoma of the pancreas.

PMID- 9169671
TI  - Sensitivity and specificity of the APC resistance assay in detection of
      individuals with factor V(Leiden)

PMID- 9169672
TI  - Teleradiology: will it transform the practice of radiology?

PMID- 9169673
TI  - Tumor angiogenesis: tutorial on implications for imaging.

PMID- 9169674
TI  - Diagnosing choledocholithiasis: how far can we push helical CT?

PMID- 9169675
TI  - Percutaneous cecostomy.

PMID- 9169676
TI  - Reports on contrast media reactions: analysis of data from reports to the U.S.
      Food and Drug Administration.
AB  - PURPOSE: To compare U.S. Food and Drug Administration (FDA) and manufacturer data
      about patient reactions to ionic and nonionic, low- and high-osmolar contrast
      media from 1990 through 1994. MATERIALS AND METHODS: Reactions to all available
      high-osmolar and four low-osmolar contrast media (ioxaglate, iohexol, iopamidol,
      and ioversol) were compared. Ioxaglate is composed of charged particles, and data
      are reported separately. Reactions were also compared with data from 1980 to
      1984, when only high-osmolar contrast media were available. RESULTS: With high
      osmolar contrast media compared with the three noncharged low-osmolar media, the
      incidence (per million examinations) was highest for all reported reactions
      (193.8 vs 44.4), severe reactions (37.4 vs 10.5), and deaths (3.9 vs 2.1). With
      high-osmolar media compared with ioxaglate, respectively, the incidence of total
      reactions was higher (193.8 vs 142.5), of severe reactions was almost the same
      (37.4 vs 33.6), and of death was lower (3.9 vs 6.4). The incidence of severe
      reactions to total reactions was higher with nonionic media (23.7%) and ioxaglate
      (23.6%) than with ionic media (19.3%). The incidence of death to severe reactions
      was 19.7% with nonionic media, 19.0% with ioxaglate, and 10.4% with high-osmolar
      media. The incidence of renal failure (as a percentage of total reports) was
      approximately 3.6 times higher with all low-osmolar contrast media (2.3%) than
      with high-osmolar media (0.6%), usually in patients with pathologic cardiac
      conditions. CONCLUSION: All of these factors merit consideration in the
      evaluation of the utility of a given contrast medium.

PMID- 9169677
TI  - Adverse events with radiographic contrast agents: results of the SCVIR Contrast
      Agent Registry.
AB  - PURPOSE: To determine prospectively the incidence of adverse events in
      angiography related to contrast agents, and the relative incidence of events with
      use of high-osmolality contrast agents (HOCAs) and low-osmolality contrast agents
      (LOCAs) and to ascertain if risk factors can help identify increased risk of an
      adverse event and patients likely to benefit from use of LOCAs. MATERIALS AND
      METHODS: From 26 high-volume institutions, data were collected on every patient
      who underwent angiography from July 1, 1990, to June 30, 1992. Information
      included demographic and risk factors, general medical status, previous
      administration of contrast media, procedural information, occurrence and
      characteristics of all adverse events up to 12 hours after procedures, and
      relation to contrast agents, treatment, and outcome. RESULTS: In 60,891 patients,
      there were 75,616 studies, 56% with nonionic LOCAs, 8% with the ionic LOCA, and
      36% with HOCAs. Most major risk factors correlated with an increased incidence of
      adverse events related to contrast media. Incidence of these adverse events
      varied with type of procedure, with a higher incidence associated with cardiac
      and interventional procedures. Overall adverse events related to contrast media
      and those for which treatment was necessary were significantly increased (P <
      .001) with use of HOCAs for all but arterial interventional procedures. Serious
      adverse events were not different between the two classes of agents except for
      cardiac procedures. Previous reaction to contrast medium was the most important
      risk factor in prediction of an adverse event. CONCLUSION: The safety benefit of
      use of LOCAs is limited. Patients most likely to benefit are those with a
      previous reaction or more than one other major risk factor. Selective use of
      LOCAs is an appropriate strategy.

PMID- 9169678
TI  - Fecal incontinence in children: treatment with percutaneous cecostomy tube
      placement--a prospective study.
AB  - PURPOSE: To evaluate the technique used for and long-term results of percutaneous
      cecostomy tube placement for the treatment of fecal incontinence in children.
      MATERIALS AND METHODS: After an initial pilot study in 15 patients, 42 additional
      patients with fecal incontinence aged 2-20 (mean, 11.5) years and weighing 9.9
      109.0 (mean, 39.2) kg underwent percutaneous cecostomy tube placement. Twenty
      nine patients had spina bifida, nine had imperforate anus, three had cloacal
      anomalies, and one had Hirschsprung disease. Mean follow-up was 265 days (range,
      8-503 days). RESULTS: Tube placement was successful in all patients. One patient
      developed local inflammation after accidental early retention-suture removal,
      which was treated with suture replacement and intravenous antibiotics. Another
      developed postprocedural ileus, which resolved. Late complications included
      constipation in one patient (treated with diet alteration), granulation tissue in
      seven patients (treated with silver nitrate cautery), and accidentally dislodged
      tubes in three patients (two successfully replaced at home and one replaced at
      the radiology suite). Vomiting related to the phosphate enema occurred in two
      patients. Resolution of soiling was achieved in all patients. CONCLUSION:
      Percutaneous cecostomy and antegrade enemas are very successful in achieving
      fecal continence and patient independence and acceptability, with minimal early
      and late complications.

PMID- 9169679
TI  - In-line pressures generated in small-bore central venous catheters during power
      injection of CT contrast media.
AB  - PURPOSE: To determine in-line pressures generated in small-bore central venous
      catheters during power injection of computed tomographic (CT) contrast media.
      MATERIALS AND METHODS: Five 3.0-7.0-F central venous catheters for pediatric
      patients were tested at full and half lengths in vitro. In-line pressures were
      measured during power injection of three contrast media. Rates of injection were
      increased in steps from 0.1 to 5.0 mL/sec or until a peak pressure of 100 psi
      (700 kPa) was achieved. The maximum tolerated flow rate was determined with
      reference to the manufacturer's suggested operating pressure limit for each
      catheter. RESULTS: At full length, the maximum tolerated flow rates were as
      follows: 2-3 mL/sec for the large lumen and 1-1.4 mL/sec for the small lumen of
      the 7.0-F double-lumen catheter; 0.2-0.4 and 0.8-1.2 mL/sec for the 3.0- and 4.0
      F peripherally inserted central catheters, respectively; 0.7-1.2 mL/sec for the
      6.6-F catheter; and only 0.2 mL/sec for the 4.2-F catheter, which ruptured during
      testing at higher flow rates. CONCLUSION: Flow rates were documented at which
      certain small-bore central venous catheters should tolerate power injection of CT
      contrast media with peak pressures remaining below the manufacturer's recommended
      operating pressure limits. These data may serve as a guide for clinical use.

PMID- 9169680
TI  - Bowel wall thickening in children: differentiation with US.
AB  - PURPOSE: To determine whether vascular, ischemic, and inflammatory causes of
      bowel wall thickening in children can be differentiated at gray-scale and color
      Doppler ultrasonography (US). MATERIALS AND METHODS: Thirty-seven children with
      acute bowel disease underwent graded compression US. Findings of bowel wall
      thickness, wall echotexture, location of bowel involvement, and presence of color
      Doppler flow were evaluated. Diagnoses were classified as inflammation (n = 25),
      vasculitis (n = 7), or ischemia (n = 5) and were confirmed with findings from
      colonoscopy and biopsy, stool culture analysis, surgery, and cutaneous biopsy,
      and with a combination of clinical and laboratory data. RESULTS: Patient age (P =
      .0022), bowel wall thickness (P = .0001), and color Doppler flow (P = .0013) were
      statistically significantly related to disease type. Wall thickening and absence
      of visible color Doppler flow suggested ischemia. Older patient age and visible
      color Doppler flow suggested inflammation, whereas younger patient age and
      visible color flow suggested vasculitis. Difference in location of bowel disease
      in patients with ischemic versus those with vascular wall thickening was
      statistically significant (P = .0185). No difference was found between disease
      type and wall stratification. CONCLUSION: Gray-scale and color Doppler flow US
      can aid in differentiating ischemic, vascular, and inflammatory bowel wall
      thickening.

PMID- 9169681
TI  - Left-sided congenital diaphragmatic hernia: value of prenatal MR imaging in
      preparation for fetal surgery.
AB  - PURPOSE: To evaluate the usefulness of prenatal magnetic resonance (MR) imaging
      in determination of the position of the fetal liver and amount of lung tissue in
      left-sided congenital diaphragmatic hernia. MATERIALS AND METHODS: In three
      pregnant women, MR imaging was performed with a 1.5-T magnet and fast gradient
      echo, half-Fourier single-shot turbo spin-echo, and echo-planar sequences. MR
      imaging findings were compared with those from ultrasound (US) performed the same
      day. The fetuses were 20, 23, and 32 weeks gestational age. RESULTS: The fetal
      liver was demonstrated in the chest in all three fetuses with MR imaging and in
      only one fetus with US. The best images of the fetal liver were obtained with a
      T1-weighted gradient-echo sequence. The best images of the entire fetus were
      obtained with a half-Fourier single-shot turbo spin-echo sequence. CONCLUSION: In
      these fetuses, MR imaging proved important by clearly demonstrating herniation of
      fetal liver into the chest, thereby changing family counseling and prenatal care.

PMID- 9169682
TI  - Third ventricle: size and appearance in normal fetuses through gestation.
AB  - PURPOSE: To define the size and appearance of the normal fetal third ventricle.
      MATERIALS AND METHODS: The third ventricle was prospectively assessed in 441
      consecutive normal second- and third-trimester fetuses. The fetuses were divided
      into six gestational age ranges. Data regarding the size and configuration of the
      third ventricle were analyzed for each group. RESULTS: The third ventricle was
      seen in 435 of 440 (98.9%) fetuses. It appeared as a single echogenic line
      between the thalami in 171 (38.9%) fetuses, as parallel echogenic lines outlining
      a fluid-filled lumen in 243 (55.2%) fetuses, and as divergent lines delineating a
      V-shaped fluid-filled structure in 21 (4.8%) fetuses. The single-line
      configuration was most common early in the second trimester. Later in pregnancy,
      the ventricle walls could be discerned as separate parallel or divergent lines
      outlining a fluid-filled lumen. The average width of the ventricle was relatively
      constant at approximately 1 mm from 12 to 28 weeks. After this time, it enlarged,
      reaching a maximum 1.9 mm. CONCLUSION: The third ventricle can be imaged in most
      second- and third-trimester fetuses. Its size and configuration evolve through
      the second and third trimesters. This evolution must be considered in the
      evaluation of normality. At any gestational age, a third ventricle greater than
      3.5 mm in width should be viewed with concern for abnormality.

PMID- 9169683
TI  - Dynamic TurboFLASH subtraction technique for contrast-enhanced MR imaging of the
      prostate: correlation with histopathologic results.
AB  - PURPOSE: To assess whether a TurboFLASH (fast low-angle shot) magnetic resonance
      (MR) sequence can improve the accuracy of fast spin-echo (SE) endorectal coil MR
      imaging in the staging and localization of prostate cancer. MATERIALS AND
      METHODS: In 57 patients with prostate cancer, MR imaging was performed with the
      following sequences: T1-weighted SE, T2-weighted fast SE, single-section
      gadolinium-enhanced dynamic subtracted TurboFLASH (one image every 1.25 or 2.5
      seconds), and late-phase gadolinium-enhanced T1-weighted SE. Retrospectively, two
      blinded independent readers graded onset and steepest slope of enhancement and
      assessed tumor involvement and capsular penetration. MR findings were correlated
      with histopathologic results. RESULTS: On TurboFLASH images, prostate cancer was
      characterized by early and rapidly accelerating enhancement compared with that of
      surrounding tissues. Average sensitivity, specificity, and accuracy for detection
      of tumor involvement for the two readers with TurboFLASH images were 73.5%,
      81.0%, and 77.5%. These values with fast SE images were 57.5%, 80.5%, and 72.0%.
      Depiction of capsular penetration and delineation and staging of tumor were
      better when TurboFLASH images were included with fast SE images. Differences
      between the two sequences, however, were not statistically significant.
      CONCLUSION: Because the TurboFLASH sequence did not statistically significantly
      improve tumor localization and staging results, routine use is not recommended.
      The technique may be useful for selected patients with equivocal evidence of
      capsular penetration.

PMID- 9169684
TI  - Prostatic cryosurgery: use of MR imaging in evaluation of success and technical
      modifications.
AB  - PURPOSE: To evaluate the usefulness of contrast material-enhanced magnetic
      resonance (MR) imaging in objective assessment of prostatic cryosurgery and the
      role of MR imaging in the modification of prostatic cryosurgical technique.
      MATERIALS AND METHODS: Thirty-eight consecutive patients with localized (T1-3,
      N0, M0) prostatic adenocarcinoma treated with prostatic cryosurgery underwent MR
      imaging without contrast enhancement before cryosurgery and unenhanced and
      gadolinium-enhanced MR imaging within 1-3 weeks after cryosurgery. The first 20
      patients also underwent MR imaging at 3 months after cryosurgery. MR imaging
      findings were correlated with those from transrectal ultrasound-directed
      prostatic staging biopsy. RESULTS: Cryonecrotic prostate was identified as
      avascular regions characterized by absolute signal void on contrast-enhanced
      images. With progressive modification of cryosurgical technique, complete
      cryoablation of the prostate was achieved in the latter nine of the 38 patients.
      When cryoablation was considered complete according to MR imaging criteria,
      findings invariably correlated with those at biopsy, with no residual prostate
      tissue or tumor. CONCLUSION: Gadolinium-enhanced MR imaging of the prostate after
      cryosurgery provides a highly accurate means of monitoring success. Objective MR
      imaging findings allow modifications to the technology and technique, resulting
      in optimal therapeutic results with prostatic cryosurgery.

PMID- 9169685
TI  - Transplanted renal artery: detection of stenosis with color Doppler US.
AB  - PURPOSE: To evaluate the influence of various parameters on peak systolic
      velocity in the transplanted renal artery and to define the normal range of peak
      systolic velocity. MATERIAL AND METHODS: Color Doppler ultrasonographic (US)
      findings in 105 patients were reviewed. There were no clinical or biologic
      findings suggestive of a stenosis in the transplanted renal artery in these
      patients. The peak systolic velocity in the transplanted renal and external iliac
      arteries and the renal resistive index were measured. RESULTS: A large range of
      peak systolic velocities was noted in the transplanted renal artery. Peak
      systolic velocity in the renal artery was statistically significantly correlated
      with that in the external iliac artery when there was no pronounced vessel
      curvature. There was no relationship between peak systolic velocity and resistive
      index or time between transplantation and US. High peak systolic velocity was
      associated with a pronounced vessel curvature. CONCLUSION: The normal range of
      peak systolic velocity in the transplanted renal artery has considerable
      variability. Because of the strong correlation, the ratio of velocity in the
      renal artery to that in the external iliac artery may be useful in detection of
      stenosis.

PMID- 9169686
TI  - Management of microcalcifications that develop at the lumpectomy site after
      breast-conserving therapy.
AB  - PURPOSE: To design a decision tree according to time from irradiation and site,
      morphology, and number of microcalcifications for the rational treatment of
      patients with microcalcifications at the lumpectomy site after breast-conserving
      therapy (BCT), to minimize performance of biopsy. MATERIALS AND METHODS: From a
      database of 504 women selected to receive BCT, those developing probably benign
      microcalcifications within 3 years of BCT received close follow-up with
      mammography. Patients developing fewer than four probably benign
      microcalcifications more than 3 years after treatment were offered mammography or
      biopsy. If microcalcifications appeared malignant or patients developed four or
      more microcalcifications after 3 years, biopsy was performed. RESULTS: Twenty
      eight patients (29 breasts [5.7%]) developed microcalcifications confined to the
      lumpectomy site. Fifteen patients (15 breasts) developed microcalcifications
      within 3 years of BCT and were followed up with mammography. Thirteen patients
      (14 breasts) developed microcalcifications confined to the lumpectomy site after
      more than 3 years. Among the latter group, microcalcifications appeared malignant
      in four breasts, and biopsy specimens revealed three recurrences. The remaining
      10 breasts were followed up with mammography. No patient undergoing mammographic
      follow-up without biopsy has had clinical evidence of local failure throughout
      the follow-up period. CONCLUSION: Follow-up mammography is an option when benign
      appearing microcalcifications develop at the lumpectomy site depending on time of
      appearance and number; it is the primary recommendation when these
      microcalcifications develop within 3 years after treatment.

PMID- 9169687
TI  - Stereotactic core biopsy of calcifications highly suggestive of malignancy.
AB  - PURPOSE: To assess stereotactic core biopsy for evaluation of Breast Imaging
      Reporting and Data System (BI-RADS) category 5 calcifications (highly suggestive
      of malignancy). MATERIALS AND METHODS: Retrospective review of mammograms
      revealed 31 women (aged 34-86 years) with BI-RADS category 5 calcifications who
      underwent 14-gauge stereotactic core biopsy with an automated gun. Records were
      reviewed to determine the frequency with which stereotactic core biopsy obviated
      a surgical procedure. Cost savings were based on Medicare estimates of $472 for
      stereotactic core biopsy and $1,335 for surgical biopsy. RESULTS: Of 31 patients,
      stereotactic core biopsy revealed carcinoma in 19 (61%), atypical ductal
      hyperplasia (ADH) in eight (26%), and benign findings discordant with
      mammographic results in four (13%). Surgical biopsy was recommended for the 12
      patients with ADH or benign but discordant core biopsy diagnoses. Of the 19
      patients with carcinoma at stereotactic core biopsy, two chose to undergo a
      second biopsy surgically, two had small foci of ductal carcinoma in situ (DCIS)
      that would have been fully excised with surgical biopsy, one with DCIS at
      stereotactic core biopsy underwent axillary dissection after invasion was found
      at surgery, and one underwent excision but had tumor at lumpectomy margins.
      Thirteen (42%) of 31 patients were spared a surgical procedure, saving $100 per
      patient. CONCLUSION: Stereotactic core biopsy with an automated gun obviated a
      surgical procedure in 42% of patients with BI-RADS category 5 calcifications,
      resulting in modest cost savings in this group.

PMID- 9169688
TI  - Breast calcification and mass detection with mammographic anode-filter
      combinations of molybdenum, tungsten, and rhodium.
AB  - PURPOSE: To determine whether contrast loss on mammograms obtained with tungsten
      (W)-molybdenum (Mo), rhodium (Rh)-Rh, and W-Rh anode-filter units affects
      calcification and mass detection relative to that on mammograms obtained with Mo
      Mo anode-filter units. MATERIALS AND METHODS: Three unfixed cadaveric breasts of
      4.0-, 5.5-, or 7.0-cm thickness were imaged with three mammographic units with Mo
      Mo, W-Mo, Rh-Rh, and W-Rh anode-filter combinations. Calcification clusters (<300
      microm in diameter) and masses (0.5-1.2 cm) placed on the cadaveric breasts
      simulated abnormal mammograms. Thirty-five images without and 57 images with
      added calcifications and masses were acquired with a 180-speed screen-film system
      and interpreted by four mammographic specialists. With a 150-speed screen-film
      system, 10 normal images and 30 abnormal images with added calcifications were
      obtained with Mo-Mo and Rh-Rh equipment and read by three of the four
      radiologists. RESULTS: For the 180-speed system, there were statistically
      significant differences (P < .05) in detection of calcifications on Mo-Mo images
      compared with W-Mo, Rh-Rh, and W-Rh images. These differences disappeared with
      the 150-speed system. For mass detection with the 180-speed system, W-Rh was
      significantly better than Mo-Mo (P = .02). CONCLUSION: Dose savings and increased
      penetration with Rh-Rh and W-Rh anode-filter combinations may decrease
      calcification detection if fast screen-film systems are used, but mass detection
      may be improved.

PMID- 9169689
TI  - Coaxial technique: approach to breast core biopsies.
AB  - PURPOSE: To assess the feasibility of the coaxial core breast biopsy technique
      performed under stereotactic and ultrasound (US) guidance in vitro and in vivo.
      MATERIALS AND METHODS: Biopsies were performed in vitro and in vivo with a
      coaxial technique. In vitro, the true needle-tip deviation was measured with a
      breast phantom on a stereotactic device with alteration of x and y axes. In vitro
      US studies were performed to evaluate the optimal technique for harvesting
      sufficient material for histologic work-up. In 205 patients, coaxial biopsy was
      performed in 210 suspicious lesions under US (61 lesions) or stereotactic
      (patient in the sitting position, n = 67; patient in the prone position, n = 82)
      guidance. In addition, the coaxial system was used for preoperative localization.
      Surgery and histologic work-up were performed in all cases. RESULTS: In vitro,
      the true needle-tip deviation was found to be less than indicated on the
      stereotactic device. A factor was introduced to correct this error. For US
      guidance, angulation or rotation of the coaxial needle within the lesion proved
      to be the best technique to increase the size of histologic specimen. Of the 210
      lesions, 112 were benign and 98 were malignant. Agreement between biopsy results
      and final postsurgical histologic analysis was found in 205 cases (98%).
      CONCLUSION: The coaxial breast biopsy technique is an accurate, simple, and time
      saving method performed under stereotactic or US guidance.

PMID- 9169690
TI  - Women with breast cancer: histologic findings in the contralateral breast.
AB  - PURPOSE: To investigate contralateral breast biopsy histologic findings in women
      with breast cancer. MATERIALS AND METHODS: Histologic findings in 237 patients
      with breast cancer who underwent contralateral breast biopsy for clinically or
      mammographically detected abnormalities were retrospectively reviewed. Malignant
      findings were categorized by histologic type. Benign findings were categorized by
      risk of breast cancer. Comparison was made with mammographically guided breast
      biopsy results in 1,294 patients without breast cancer. RESULTS: Of the 237
      patients, 168 (70.9%) had either malignancy or high-risk histologic findings. One
      hundred thirty-nine patients (58.6%) had malignant findings; 98 (41.4%) had
      benign findings. Of the 98 with benign findings, 29 (30%) had high-risk
      histologic findings. Thirty (33%) of the 91 patients with invasive cancer had
      invasive lobular carcinoma. Forty-seven (45.6%) of the 103 patients with
      malignant lesions at mammographically guided biopsies had ductal carcinoma in
      situ alone. CONCLUSION: Compared with biopsy in women without breast cancer,
      contralateral biopsy in women with breast cancer was more likely to show
      malignancy, invasive lobular carcinoma, or ductal carcinoma in situ alone (P <
      .001) or to show high-risk histologic benign findings (P < .001). Mammographic
      and clinical findings in the contralateral breast should be regarded as more
      suspicious than those in patients without known breast cancer.

PMID- 9169691
TI  - Graduates speak: the employment experience of 1995 graduates of diagnostic
      radiology and radiation oncology training programs.
AB  - PURPOSE: To determine the initial employment experience of 1995 graduates of
      radiology programs. MATERIALS AND METHODS: A questionnaire was mailed to all
      graduates of radiation oncology programs and to a stratified, random sample of
      600 graduates of diagnostic radiology programs. The final response rate was 66%.
      RESULTS: After graduation, 4%-10% of graduates worked for a period as locum
      tenens, worked in a job unrelated to radiology, or were unemployed. Immediate
      postgraduation unemployment was 2%-5%; 7-12 months later, it was less than 0.5%.
      Median actual salary was approximately equal to median expected salary. Radiation
      oncology fellowship graduates often had poorer outcomes. Almost half of the
      graduates with posttraining employment had a job with at least one characteristic
      regarded as unfavorable by some commentators (most commonly, undesirable location
      or no opportunity to become a partner), and at least one-fifth had and disliked
      such a characteristic. Geographic constraints, including the need to find
      employment for a spouse or companion, did not adversely affect employment
      outcome. CONCLUSION: Eventual unemployment was low, and starting salaries have
      not collapsed. Generally, the implications of job characteristics are best
      assessed by monitoring trends, but the prevalence of non-partnership track
      employment may well have increased.

PMID- 9169692
TI  - Patients with emphysema: quantitative CT analysis before and after lung volume
      reduction surgery. Work in progress.
AB  - PURPOSE: To quantitatively assess the morphologic changes in the lungs after lung
      volume reduction surgery and determine whether changes at quantitative computed
      tomography (CT) reflect changes in lung function. MATERIALS AND METHODS: In 10
      patients, chest CT images were obtained at full inspiration and expiration before
      and after surgery. A semiautomated segmentation method was developed to isolate
      the lung regions and calculate the lung volumes and frequency distribution of
      attenuation values. The changes in lung volume and attenuation after surgery were
      compared with clinical findings, and an exploratory evaluation of outcome
      predictors was conducted. RESULTS: Semiautomated segmentation and quantitative
      analysis compared favorably with manual techniques, and there was good
      correlation between the emphysema indexes and percentage predicted forced
      expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital
      capacity, and diffusing capacity. The emphysema index decreased from 60% to 38%
      at inspiration and from 60% to 27% at expiration after surgery. The average CT
      lung volume decreased from 7.5 to 5.6 L at inspiration (25%) and from 6.4 to 3.8
      L (41%) at expiration after surgery and correlated well with measurements at
      plethysmography. CONCLUSION: Substantial decreases in the lung volumes and
      emphysema index, increased airflow, possible reexpansion of some remaining lung,
      and the relation between preoperative quantitative CT indexes and clinical
      outcome suggest a multifactorial mechanism for improvement seen after surgery.

PMID- 9169693
TI  - Acute eosinophilic pneumonia: radiologic and clinical features.
AB  - PURPOSE: To determine the radiographic and computed tomographic (CT)
      characteristics of acute eosinophilic pneumonia. MATERIALS AND METHODS: Twelve
      consecutive patients with acute eosinophilic pneumonia were included in the
      study. The diagnosis was based on clinical symptoms and results of
      bronchoalveolar lavage. Plain chest radiographs were obtained in all patients; CT
      scans were obtained in three patients. Two thoracic radiologists reviewed the
      radiographs and CT scans. RESULTS: Ten patients had bilateral areas of air-space
      opacity on images obtained at presentation; in seven of these patients,
      interstitial areas of opacity were also present. Two patients had bilateral
      interstitial areas of opacity and no areas of air-space opacity. Interlobular
      septal thickening and ground-glass attenuation were present on CT scans in two
      patients; patchy bilateral consolidation was present on CT scans in one patient.
      Pleural effusion was present on radiographs in seven patients (58%) and was
      bilateral in five. Pleural effusion was present at some point during the course
      of disease in all patients. In all patients, air-space disease markedly improved
      within 3 days of initiation of treatment with corticosteroids. CONCLUSION: Acute
      eosinophilic pneumonia should be considered as a possible diagnosis when a
      previously healthy person presents with acute respiratory failure of unknown
      origin.

PMID- 9169694
TI  - Obliterative bronchiolitis: individual CT signs of small airways disease and
      functional correlation.
AB  - PURPOSE: Individual features of small airways disease depicted at computed
      tomography (CT) were correlated with functional indexes in patients with
      obliterative bronchiolitis. MATERIALS AND METHODS: Fifteen patients (all women)
      who fulfilled the strict criteria for diagnosis of obliterative bronchiolitis
      underwent thin-section CT at full inspiration and at end expiration. The CT scans
      were scored by two observers for extent of decreased attenuation of the lung
      parenchyma; end-expiration CT signs of air trapping; and bronchial dilation, wall
      thickening, and mucous plugging. The functional importance of each CT sign was
      evaluated. RESULTS: Areas of decreased attenuation were present in all patients
      (median score at end expiration, 61%; range, 21%-83%). Bronchial wall thickening
      was identified in 13 of the 15 patients. Correlations of the extent of decreased
      attenuation and measures of air-flow obstruction were strongest between decreased
      attenuation at end expiration and air flow at low lung volumes (r(s) = -.70, P <
      .005). This relationship remained intact after correction for the severity of
      bronchial wall thickening. CONCLUSION: In patients with obliterative
      bronchiolitis, the extent of decreased attenuation at CT was most strongly
      related to depression of pulmonary function tests of the small airways. Decreased
      attenuation is the cardinal sign for further quantitative studies of obliterative
      bronchiolitis.

PMID- 9169695
TI  - Thoracoabdominal aorta in Marfan syndrome: MR imaging findings of progression of
      vasculopathy after surgical repair.
AB  - PURPOSE: To determine the natural history of vasculopathy of the thoracoabdominal
      aorta in patients with Marfan syndrome after composite graft repair of the aortic
      root. MATERIALS AND METHODS: A total 224 magnetic resonance (MR) images obtained
      in 48 patients with Marfan syndrome over a period of 2.3-9.4 years (mean, 5.0
      years) were retrospectively reviewed. On each image, the diameter of the
      thoracoabdominal aorta was measured and the presence of dissection or major
      peripheral artery aneurysms was determined. RESULTS: In 31 (65%) of the 48
      patients, no statistically significant change (3 mm or less increase in diameter)
      in the diameter of the aorta occurred during the study (group 1); in the
      remaining 17 (35%) patients, a significant change occurred (greater than 3 mm
      increase) (group 2). The mean initial diameter of the native aorta was slightly
      larger in group 2 (mean, 27 mm +/- 8 [standard deviation]) than in group 1 (mean,
      23 mm +/- 6). In group 1, the mean rate of dilation was 0.07 mm/y +/- 0.2; in
      group 2, the rate was 2.3 mm/y +/- 3.3. Two patients with aortic dissection were
      in group 1, whereas 14 such patients were in group 2 (P < .001). Aneurysms that
      involved major peripheral arteries were present in four (13%) of the 31 group 1
      patients and in 12 (71%) of the 17 group 2 patients (P < .001). Surgical
      intervention was necessary in two group 1 patients and in 14 group 2 patients (P
      < .001). CONCLUSION: A subset of patients with Marfan syndrome manifested
      multiple forms of vasculopathy, including progressive aortic dilation,
      dissection, and peripheral artery aneurysm after composite aortic graft repair of
      the ascending aorta. Patients with these characteristics merit more frequent MR
      follow-up since further surgery was often necessary in these individuals.

PMID- 9169696
TI  - Prospective navigator correction of image position for coronary MR angiography.
AB  - PURPOSE: To determine the potential benefit of prospective navigator correction
      of image position for coronary magnetic resonance (MR) angiography. MATERIALS AND
      METHODS: Two-dimensional MR angiograms were obtained with free breathing in 12
      adult subjects. Navigator gating was used with and without prospective correction
      and with gating windows set at 3, 5, and 7 mm. MR angiograms were compared with
      those obtained with conventional, end-expiratory breath holding. RESULTS:
      Navigator gating with correction resulted in image quality equivalent to that
      obtained with breath holding, even with the 7-mm gating window. In contrast,
      navigator gating without correction allowed only maintenance of image quality
      similar to that obtained with breath holding for the 3- and 5-mm windows and
      resulted in decreased image quality with the 7-mm window (P < .05). Use of
      navigator gating with correction and the 7-mm window resulted in a 28% decrease
      in imaging time compared with breath holding and a 33% decrease compared with the
      3-mm gating window (P < .05 for both comparisons). CONCLUSION: Prospective,
      adaptive navigator correction of image position for free-breathing coronary MR
      angiography is a promising, novel approach to compensate for respiratory motion.

PMID- 9169697
TI  - Small arterial-portal venous shunts: a cause of pseudolesions at hepatic imaging.
AB  - PURPOSE: To compare hepatic angiographic findings of small arterial-portal venous
      shunts with those of other imaging modalities, and to determine whether these
      shunts are related to hepatocellular carcinoma. MATERIALS AND METHODS: At hepatic
      angiography in 223 patients, small arterial-portal venous shunts not directly
      related to hepatocellular carcinoma and focal areas of parenchymal contrast
      material enhancement more than 1 cm in diameter were found in 28 patients. These
      28 patients were prospectively evaluated with computed tomography (CT) during
      arterial portography (CTAP) (n = 12), CT after iodized oil administration (n =
      23), intraoperative ultrasonography (n = 5), or follow-up hepatic angiography (n
      = 13). Magnetic resonance (MR) images (n = 10) and dynamic CT scans (n = 4) in
      these patients were retrospectively reviewed. RESULTS: Arterial-portal venous
      shunts noted at angiography manifested as perfusion defects at CTAP in 10
      patients and as an area of arterial contrast enhancement at dynamic CT in three
      patients. No lesion was seen at MR imaging, and no persistent iodized oil uptake
      was seen at CT. There was no evidence of hepatocellular carcinoma tumor growth
      around the shunts at follow-up angiography, and no tumor was present at surgery.
      CONCLUSION: Understanding of the hemodynamic changes caused by these small shunts
      can aid in the interpretation of vascular imaging findings.

PMID- 9169699
TI  - Benign and malignant esophageal strictures: treatment with a polyurethane-covered
      retrievable expandable metallic stent.
AB  - PURPOSE: To evaluate the clinical effectiveness of a polyurethane-covered,
      retrievable, self-expandable metallic stent and hook catheter in the treatment of
      esophageal strictures. MATERIALS AND METHODS: Stents were constructed of 0.4-mm
      stainless steel wire in a cylindric zig-zag configuration of six to nine bends.
      Four to eight stents were connected in tandem by dipping in a polyurethane
      solution. A nylon loop was hooked inside to each bend of the proximal portion of
      the stent and strung with a thread. Under fluoroscopic guidance, 22 stents were
      placed in 16 patients with a malignant stricture and five patients with a benign
      stricture. The stent was removed with a hook catheter 2 months after placement in
      patients with a benign stricture and when complications occurred in patients with
      a malignant stricture. All patients had dysphagia with ingestion of soft foods or
      liquids. RESULTS: Stent placement was technically successful and well tolerated
      in 20 patients. In one patient, the stent was misplaced but relocated
      successfully. After stent placement, all patients were able to ingest solid
      and/or soft foods without dysphagia. After stent removal, strictures showed
      improvement but recurred in two patients. CONCLUSION: Use of polyurethane
      covered, retrievable expandable stents seems to be a feasible and effective
      method of treatment of benign and malignant esophageal strictures.

PMID- 9169700
TI  - Detection of choledocholithiasis: comparison of unenhanced helical CT and
      endoscopic retrograde cholangiopancreatography.
AB  - PURPOSE: To compare unenhanced helical computed tomography (CT) and endoscopic
      retrograde cholangiopancreatography (ERCP) in the detection of common bile duct
      calculi. MATERIALS AND METHODS: Within 13 months, 51 patients (aged 18-94 years)
      with clinically suspected choledocholithiasis underwent unenhanced helical CT
      immediately before undergoing ERCP. CT scans were evaluated for the presence of
      bile duct stones, ampullary stones, the gallbladder and gallbladder stones,
      intrahepatic biliary dilatation, and the size of the bile duct at the porta
      hepatis and in the pancreatic head. ERCP images were evaluated for the presence
      of bile duct or ampullary stones, as well as for biliary dilatation. RESULTS:
      Unenhanced helical CT depicted common bile duct stones in 15 of 17 patients found
      to have stones at ERCP. Three patients had stones impacted at the ampulla, all of
      which were detected with CT. In addition, there was one false-positive finding at
      CT. CT had a sensitivity of 88%, a specificity of 97%, and an accuracy of 94% in
      the diagnosis of common bile duct stones. CONCLUSION: Unenhanced helical CT is
      useful for evaluating suspected choledocholithiasis.

PMID- 9169698
TI  - Adventitial cystic disease of the popliteal artery: percutaneous US-guided
      aspiration.
AB  - PURPOSE: To evaluate percutaneous ultrasound (US)-guided aspiration as an
      alternative therapy for adventitial cystic disease. MATERIALS AND METHODS:
      Between September 1993 and June 1996, seven patients (six men, one woman; age
      range, 42-62 years; mean age, 48 years) presented with symptomatic adventitial
      cystic disease of the popliteal artery (one patient with subacute foot
      paresthesia, six patients with chronic calf claudication). Color Doppler
      sonography showed stenosis due to eccentric cysts. Five of the patients also
      underwent digital subtraction angiography, and four patients underwent magnetic
      resonance imaging. With real-time sonographic guidance, a 14-gauge needle was
      forwarded percutaneously into the cysts for aspiration. The aspiration procedure
      was performed on an outpatient basis with local anesthetics. RESULTS: The
      procedure was technically and clinically successful in all cases. No
      complications were noted. Follow-up color duplex sonography performed between 1
      and 32 months (mean, 14.8 months) after the procedure showed no relevant
      recurrent stenosis. CONCLUSION: Percutaneous US-guided aspiration is an easy,
      safe, efficacious method for treating adventitial cystic disease. In symptomatic
      patients who do not have thrombotic occlusion, it may be considered the treatment
      of choice.

PMID- 9169701
TI  - Hepatic lesion detection at MR imaging: a comparative study with four sequences.
AB  - PURPOSE: To compare results with the following magnetic resonance (MR) imaging
      sequences in the detection of focal hepatic lesions: fast spin-echo (SE) before
      and after administration of superparamagnetic iron oxide (SPIO) particles, fat
      suppressed T2-weighted SE, and dynamic gadolinium-enhanced fast low-angle shot
      (FLASH). MATERIALS AND METHODS: In 26 patients with known malignancy and
      documented focal liver lesions, 1.0-T MR imaging was performed prior to hepatic
      resection. All images were reviewed independently by four blinded observers.
      Sensitivity was calculated for each sequence and for each observer by means of
      alternative-free-response receiver operating characteristic (ROC) methods.
      RESULTS: The mean area under the alternative-free-response ROC curve with SPIO
      enhanced fast SE (0.85) was significantly greater (P < .02) than that with all
      other sequences. Detection was significantly improved with SPIO-enhanced fast SE
      compared with dynamic gadolinium-enhanced FLASH (which was the best of the other
      three sequences) for all lesions (P < .002) and for malignant lesions (P <
      .0002). CONCLUSION: Findings with the SPIO-enhanced fast SE sequence improved
      detection of focal liver lesions and had the highest diagnostic accuracy.

PMID- 9169702
TI  - Liver T2-weighted MR imaging: comparison of fast and conventional half-Fourier
      single-shot turbo spin-echo, breath-hold turbo spin-echo, and respiratory
      triggered turbo spin-echo sequences.
AB  - PURPOSE: T2-weighted spin-echo (SE) magnetic resonance imaging in the liver was
      compared with four sequences: fast and conventional half-Fourier single-shot
      turbo SE (HASTE) and breath-hold and respiratory-triggered turbo SE. MATERIALS
      AND METHODS: In 58 patients with focal liver lesions, imaging was performed with
      a 1.5-T magnet and a phased-array coil. Images obtained with fast HASTE
      conventional HASTE, breath-hold turbo SE, and respiratory-triggered turbo SE were
      compared. Results of quantitative, qualitative, and receiver operating
      characteristic analyses were compared. RESULTS: Lesion-to-liver contrast for
      solid tumors was significantly higher with the fast HASTE and respiratory
      triggered turbo SE sequences than with the conventional HASTE and breath-hold
      turbo SE sequences (P < .01) and for cystic lesions was significantly higher with
      the conventional and fast HASTE sequences than with the breath-hold or
      respiratory-triggered turbo SE sequences (P < .01). Artifacts were negligible on
      all fast and conventional HASTE images. In receiver operating characteristic
      analyses, diagnostic performance was significantly higher with the fast HASTE and
      respiratory-triggered turbo SE sequences than with the conventional HASTE and
      breath-hold turbo SE sequences (P < .01). CONCLUSION: Images obtained with the
      fast HASTE sequence were free from motion artifacts, and observer diagnostic
      performance was similar to that with the respiratory-triggered turbo SE sequence.

PMID- 9169703
TI  - Pancreatic fluid collections prior to intervention: evaluation with MR imaging
      compared with CT and US.
AB  - PURPOSE: To evaluate the ability of magnetic resonance (MR) imaging to depict
      solid debris within pancreatic collections prior to intervention and to help
      assess drainability, as well as to compare MR findings with those obtained at
      computed tomography (CT) and ultrasound (US). MATERIALS AND METHODS: Nineteen
      collections in 18 patients were evaluated with MR imaging, CT, and US prior to
      drainage. Prospective, blinded interpretations of imaging studies by three
      independent readers (each interpreted all the images obtained with only one
      modality) evaluated collection characteristics (debris, consistency, septation,
      wall thickness, and irregularity) and predicted drainability. Findings were
      compared with clinical diagnosis and clinical outcome of drainage. RESULTS: MR
      imaging and CT depicted all collections; US failed to depict two collections. In
      nine patients with subacute necrotic collections, solid debris was seen in eight
      (89%) at MR imaging, in two (22%) at CT, and in eight (89%) at US. In seven
      patients with pseudocysts, debris was seen in two (28%) at MR imaging and in none
      at CT, as well as in six (100%) of six at US. A collection was defined as "not
      drainable" on the basis of the depiction of solid necrotic debris more than 1 cm
      in diameter. With this definition, statistically significant differences between
      sensitivity and specificity values, respectively, were found for the prediction
      of actual drainability: MR imaging, 100% and 100%; CT, 25% and 100%; US, 88% and
      54%. CONCLUSION: Predrainage MR imaging should be performed in patients with
      subacute pancreatic collections to avoid infectious complications from
      unrecognized necrotic debris that cannot be removed with use of standard
      pseudocyst drainage techniques.

PMID- 9169704
TI  - Undifferentiated (embryonal) sarcoma of the liver: pathologic basis of imaging
      findings in 28 cases.
AB  - PURPOSE: To correlate the imaging and pathologic features of undifferentiated
      (embryonal) sarcoma (UES) and account for the discrepancy between the solid
      appearance at ultrasound (US) and the almost cystlike appearance at computed
      tomography (CT) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: The
      clinical, pathologic, and imaging findings in 28 patients (age range, 3-49 years)
      with pathologically proved UES were retrospectively reviewed. All patients
      underwent at least one cross-sectional imaging study to include CT (27 patients),
      US (21 patients), and MR imaging (six patients). Tumor size, gross morphology (n
      = 27), histologic features, and proportion of solid and cystlike components were
      evaluated and correlated to the imaging findings. RESULTS: The mean transverse
      diameter of the tumors was 14 cm (range, 10-25 cm). At gross examination, the
      tumors were predominantly solid (mean, 83% of tumor volume), and pathologic and
      US findings were concordant. Conversely, CT scans showed low attenuation
      (approximately that of water) in 88% of the tumor volume and T2-weighted MR
      images showed high signal intensity (approximately equal to that of cerebrospinal
      fluid) in 89% of the tumor volume. CONCLUSION: UES shows a misleading cystlike
      appearance at CT and MR imaging compared with US and pathologic findings. In a
      child or young adult with a liver tumor, this finding is useful in making a
      prospective diagnosis and avoiding misguided attempts at drainage.

PMID- 9169705
TI  - Peritumoral tissue reaction at transrectal US as a possible cause of overstaging
      in rectal cancer: histopathologic correlation.
AB  - PURPOSE: To assess if peritumoral tissue reaction (PTR) can be differentiated
      from tumor with transrectal ultrasound (TRUS) to avert overstaging. MATERIALS AND
      METHODS: Preoperative TRUS results in 40 consecutive patients with biopsy-proved
      rectal cancer were compared with histopathologic reports on the specimens (study
      1). To test the hypothesis that areas more anechoic than the tumor were deemed
      responsible for incorrect staging in study 1, a prospective study was undertaken
      in another 40 consecutive patients (study 2). The thickest part of PTR was
      measured, and results were compared with the histopathologic findings. RESULTS:
      In study 1, 28 (70%) of 40 rectal cancers were staged correctly with TRUS. PTR
      was responsible for the misinterpretation in six of seven overstaged cases. In
      study 2, 38 (95%) of 40 cancers were staged correctly, and the presence or
      absence of PTR was described in 39 cases (98%). A statistically significant
      positive correlation was noted between histopathologic classification of PTR and
      its thickness measured with TRUS (P = .0001). CONCLUSION: Because of its more
      anechoic appearance, PTR may be differentiated from the tumor by means of TRUS.
      This may lead to a statistically significantly higher accuracy of TRUS in the
      staging of rectal cancer due to the avoidance of overstaging.

PMID- 9169706
TI  - Abdomen after a Puestow procedure: postoperative CT appearance, complications,
      and potential pitfalls.
AB  - PURPOSE: To evaluate the postoperative computed tomographic (CT) appearance,
      complications, and potential pitfalls after a Puestow procedure (lateral side-to
      side pancreaticojejunostomy). MATERIALS AND METHODS: Forty CT examinations were
      performed after the Puestow procedure in 20 patients. Images were retrospectively
      reviewed by three radiologists. RESULTS: The pancreaticojejunal anastomosis was
      identified at 30 examinations and was immediately anterior to the pancreatic body
      or tail. The anastomosis contained fluid or gas on 11 scans and oral contrast
      material on four scans. On 15 scans, the anastomosis appeared as collapsed bowel
      without gas, fluid, or oral contrast material. The Roux-en-Y loop was identified
      on 28 (70%) scans and contained fluid or gas on 16 scans and oral contrast
      material on six scans. The Roux-en-Y loop appeared as collapsed bowel on six
      scans. When the anastomosis or Roux-en-Y loop contained fluid and gas, the
      appearance mimicked that of a pancreatic or parapancreatic abscess.
      Peripancreatic stranding was present on 28 scans and was due to either ongoing
      pancreatitis or postoperative change. Complications included 15 transient fluid
      collections, three abscesses, four pseudocysts, one hematoma, and one small-bowel
      and Roux-en-Y obstruction. CONCLUSION: Knowledge of the anatomy after a Puestow
      procedure is essential for accurate interpretation of CT scans.

PMID- 9169707
TI  - Lymphoma: role of whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in nodal
      staging.
AB  - PURPOSE: To compare 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) positron
      emission tomography (PET) with computed tomography (CT) in primary nodal staging
      of malignant lymphoma. MATERIALS AND METHODS: Sixty consecutive patients with
      untreated, histopathologically proved malignant lymphoma (aged 7-72 years; 33
      with non-Hodgkin lymphoma, 27 with Hodgkin disease) underwent FDG PET and
      contrast material-enhanced CT for nodal staging. Lymph node regions identified at
      both CT and PET were regarded as actual locations of disease. Discordant results
      were verified with biopsy or clinical follow-up whenever possible. RESULTS: One
      hundred sixty of 740 evaluated lymph node regions were identified as diseased at
      both CT and PET. Of the 25 additional regions seen with PET, seven were true
      positive; two, false-positive; and 16, unresolved. CT showed six additional
      disease manifestations; three were false-positive, and three were unresolved.
      Staging was changed in the four patients with the seven confirmed additional PET
      findings: from stage I to II in one patient and from stage II to III in three
      patients. Staging was changed from stage II to I in one of the three patients
      with false-positive CT findings. CONCLUSION: FDG PET may be more accurate for
      detecting nodal lymphoma than incremental CT.

PMID- 9169708
TI  - CT analysis of bowed stringed instruments.
AB  - PURPOSE: To determine the utility of computed tomography (CT) for the noninvasive
      evaluation of bowed stringed instruments. MATERIALS AND METHODS: Thirty-seven
      instruments that ranged in quality from student instruments to exquisite
      Stradivarius violins were analyzed with CT. Accuracy of thickness measurements
      was determined from 24 measurements of cross-sectional pieces sawed from a
      student violin. Accuracy of density measurements was determined from 328 CT
      attenuation measurements of 16 woods used in stringed instruments. RESULTS:
      Substantial differences of normal structure were noted between the masterpieces
      crafted in Cremona, Italy, and factory-produced student instruments. Unexpected
      defects were detected in nine of 14 instruments older than 100 years and ranged
      from a few wormholes (eight instruments) to many wormholes and extensive repair
      (one violin). CT thickness and attenuation measurements correlated well to the
      line of identity with actual measurements (P < .0001). Two cellos and a viola
      have been constructed from CT-derived information. The viola was awarded a gold
      medal at a recent international competition. CONCLUSION: CT provides the modern
      luthier and acoustic scientist with a unique tool for characterization of normal
      structure, defects, and repair and for accurate measurements of wood thickness
      and density. CT-derived information aids in the replication of original
      masterpieces. CT evaluation may have an important role in the valuation,
      insurance, and identification of valuable stringed instruments.

PMID- 9169709
TI  - Intracranial aneurysms: detection and characterization with MR angiography with
      use of an advanced postprocessing technique in a blinded-reader study.
AB  - PURPOSE: To assess magnetic resonance (MR) angiography for the detection and
      characterization of angiographically proved intracranial aneurysms by using an
      advanced method of postprocessing, in a blinded-reader study. MATERIALS AND
      METHODS: One hundred fifty-eight vessels were examined with catheter angiography
      and three-dimensional time-of-flight MR angiography in 44 patients with 63
      aneurysms and 15 patients with no aneurysm at catheter angiography.
      Postprocessing was performed off-line with an advanced multifeature-extraction,
      ray-tracing algorithm. MR angiograms were interpreted independently by three
      neuroradiologists blinded to the catheter angiographic results for presence,
      location, size, and morphology of the aneurysm. Proof of diagnosis was consensus
      reading of catheter angiograms. RESULTS: Mean sensitivity for detection of
      aneurysms was 75% (range, 70%-79%). As a screening tool (ie, detection of at
      least one aneurysm necessitating catheter angiography), mean sensitivity was 91%
      for all aneurysms and 95% for aneurysms larger than 3 mm. This method was not
      adequate for detection of lobulation or size of aneurysm. CONCLUSION: MR
      angiography with an advanced method of postprocessing can result in highly
      sensitive, specific studies for the diagnosis of intracranial aneurysms that are
      of sufficient size to be considered for surgical treatment, but it is inadequate
      for characterization of aneurysms.

PMID- 9169710
TI  - Persistent low back pain in patients suspected of having herniated nucleus
      pulposus: radiologic predictors of functional outcome--implications for treatment
      selection.
AB  - PURPOSE: To assess the relationship between imaging findings, therapy, and
      functional outcome in patients with persistent low back pain who are suspected of
      having herniated nucleus pulposus. MATERIALS AND METHODS: Data collected during a
      multicenter, longitudinal study were retrospectively analyzed (n = 1,084).
      Multivariate regression was used to determine the association between imaging
      findings, therapy, and functional outcome. The patient outcome measure was
      disability days: the number of days the patient was unable to perform work
      related activities. RESULTS: In patients with at least one normal advanced
      (imaging other than plain radiography) diagnostic study or with an unconfirmed
      diagnosis of herniated nucleus pulposus, outcome at 2-year follow-up was no
      better in patients who were treated than in those who were not. In patients with
      only abnormal advanced imaging results or with a concordant diagnosis based on
      clinical and imaging findings, outcome was better in patients who underwent
      surgery than in those treated nonsurgically. Patients with a free fragment,
      protrusion, or extrusion that was treated surgically had fewer disability days
      than patients treated nonsurgically. CONCLUSION: Advanced diagnostic imaging
      studies can play an important role in treatment selection in patients with
      persistent low back pain who are suspected of having herniated nucleus pulposus.

PMID- 9169711
TI  - Hemorrhagic and nonhemorrhagic stroke: diagnosis with diffusion-weighted and T2
      weighted echo-planar MR imaging.
AB  - PURPOSE: To determine if diffusion- and T2-weighted echo-planar magnetic
      resonance (MR) imaging can be used to detect acute hemorrhagic stroke and to
      differentiate hemorrhagic from nonhemorrhagic stroke. MATERIALS AND METHODS: A
      total of 118 examinations (diffusion- and T2-weighted MR imaging) in 19 patients
      with 27 nonhemorrhagic strokes and in six patients with seven hemorrhagic strokes
      were performed. The ratios of apparent diffusion coefficient and of signal
      intensity on T2-weighted MR images in lesions to those in contralateral control
      areas were calculated. RESULTS: Decreased ADC was shown in lesions of acute (0-3
      days) hemorrhagic stroke, as well as in lesions of acute nonhemorrhagic stroke.
      Hypointense areas were seen on T2-weighted MR images in patients with acute
      hemorrhagic stroke, in contrast to normal to increased signal intensity in those
      with acute nonhemorrhagic stroke. Apparent diffusion coefficient tended to remain
      decreased in hemorrhagic stroke lesions even 100 days after onset, in contrast to
      the increased coefficient in nonhemorrhagic stroke lesions at the late chronic
      stage (31 days or older). CONCLUSION: Diffusion- and T2-weighted echo-planar MR
      imaging can be used to detect and distinguish between acute hemorrhagic and
      nonhemorrhagic stroke.

PMID- 9169712
TI  - Frontotemporal dementia and early Alzheimer disease: differentiation with frontal
      lobe H-1 MR spectroscopy.
AB  - PURPOSE: To evaluate cerebral biochemical abnormalities in patients with
      frontotemporal dementia and Alzheimer disease and to determine whether proton
      (hydrogen-1) magnetic resonance (MR) spectroscopy can help differentiate among
      these two patient groups and healthy (control) subjects. MATERIALS AND METHODS:
      MR imaging and H-1 MR spectroscopy were performed in 14 patients with
      frontotemporal dementia, 12 with probable Alzheimer disease (Alzheimer), and 11
      healthy (control) elderly subjects. Spectra were acquired from midfrontal and
      temporoparietal gray matter with a double spin-echo sequence (repetition time,
      3,000 msec; echo time, 30 msec). Results were expressed in metabolite
      concentrations corrected for the presence of cerebrospinal fluid. RESULTS: In
      frontotemporal dementia patients, the frontal lobe showed reduced N-acetyl
      compounds (-28%) and glutamate plus glutamine (-16%), suggestive of neuron loss,
      and increased myo-inositol (MI) (+19%), suggestive of increased glial content. In
      three frontotemporal dementia patients, a lactate peak was present in the frontal
      lobe. In Alzheimer patients, no statistically significant abnormalities were
      observed in the frontal region, but MI was elevated (+8%) in the temporoparietal
      region. With use of linear discriminant analysis of MR spectroscopy data alone,
      92% of the frontotemporal dementia patients were correctly differentiated from
      the Alzheimer patients and control subjects. The overall accuracy for
      discrimination among all three groups was 84%. CONCLUSION: H-1 MR spectroscopy
      demonstrated biochemical abnormalities in patients with frontotemporal dementia
      and aided differentiation between patients with frontotemporal dementia and
      Alzheimer disease.

PMID- 9169713
TI  - Evaluation of an on-line patient exposure meter in neuroradiology.
AB  - PURPOSE: To assess the clinical performance and usefulness of an on-line patient
      exposure meter installed on a neuroradiologic biplane imaging system. MATERIALS
      AND METHODS: A commercial on-line patient exposure meter was installed on each
      plane of a biplane neuroradiologic imaging system. The meter computed skin
      exposures on the basis of selected technique factors (tube potential and current)
      and information about patient location relative to the x-ray tube. Simulations
      were performed to measure the system accuracy with an angiographic
      anthropomorphic head phantom with the skin exposures measured with an ionization
      chamber. Skin doses were computed for 114 consecutive patients who underwent
      diagnostic and interventional neuroradiologic procedures. RESULTS: Agreement
      between measured and computed skin exposures in fluoroscopy, plain radiography,
      and digital imaging was generally within 5% of the true skin dose. For all
      fluoroscopic and radiographic procedures, total median skin doses were 1.20 and
      0.64 Gy for the frontal and lateral planes, respectively. In both planes, patient
      skin doses resulted primarily from digital subtraction angiographic acquisitions.
      In 29 (25%) patients, the skin dose exceeded 2.00 Gy, but no radiation-induced
      deterministic effects were observed. CONCLUSION: An on-line patient exposure
      meter can provide accurate radiation skin dose data in patients undergoing
      diagnostic and therapeutic neuroradiologic procedures.

PMID- 9169714
TI  - Interstitial laser photocoagulation of osteoid osteomas with use of CT guidance.
AB  - PURPOSE: To evaluate interstitial laser photocoagulation (a minimally invasive
      percutaneous technique of thermal destruction of deep-seated tumors, with low
      power laser energy) in local destruction of osteoid osteoma, with computed
      tomographic (CT) guidance. MATERIALS AND METHODS: Fifteen patients (age range, 8
      48 years) with presumed osteoid osteoma were treated with CT-guided interstitial
      laser photocoagulation of the nidus. A high-power semiconductor diode laser (805
      nm) with a 400-microm optical fiber was used. The fiber was introduced into the
      nidus through an 18-gauge needle. Around the fiber tip, well-defined coagulative
      necroses from 5 to 9 mm (energy delivery, 400-1,000 J) were obtained. RESULTS:
      Fourteen patients had complete pain relief, which was apparent within 24 hours in
      eight patients. One patient had recurrence of pain after 6 weeks. The remaining
      nidus was treated a second time, with complete relief. Treatment was unsuccessful
      in one patient, and surgical excision was performed. Daily activities were not
      restricted after the intervention. All patients were followed up for more than 1
      year, with no sign of recurrence. The only notable complication was a mild reflex
      sympathetic dystrophy of the wrist in one patient. Sclerosis of the nidus was
      observed 4-6 months after the procedure. CONCLUSION: Percutaneous interstitial
      laser photocoagulation of osteoid osteoma seems to be a promising, simple,
      precise, and minimally invasive alternative to traditional surgical and
      percutaneous ablations.

PMID- 9169715
TI  - Osteomyelitis of the diabetic foot: MR imaging-pathologic correlation.
AB  - PURPOSE: To evaluate the efficacy of magnetic resonance (MR) imaging for the
      diagnosis of osteomyelitis in the diabetic foot by using anatomic and histologic
      studies of the resected tissue as a standard of reference. MATERIALS AND METHODS:
      Thirteen diabetic patients with high clinical suspicion of osteomyelitis
      underwent a total of 15 MR examinations before surgery. Correlation was made
      between MR findings and the histologic features of the resected tissue, which
      included 57 bones. RESULTS: Maximum signal intensity on the T2-weighted or short
      inversion time inversion-recovery images of the bones was due to osteomyelitis
      (prospective sensitivity, 90%; specificity, 71%). Eighteen bones with increased
      signal intensity showed only edema of the marrow. The range of signal intensity
      in edema overlapped that in osteomyelitis but was lower. The use of gadopentetate
      dimeglumine improved delineation of soft-tissue inflammatory masses, but this
      contrast material was not useful in distinguishing osteomyelitis from edema.
      CONCLUSION: Marrow edema cannot be reliably distinguished from osteomyelitis with
      MR imaging. Gadopentetate dimeglumine is of limited use. Some previously
      published false-positive reports of osteomyelitis were most likely due to edema
      of the marrow. MR imaging is useful in planning surgery of the infected diabetic
      foot, as it enables reliable distinction between normal and abnormal areas.

PMID- 9169716
TI  - Pseudodefect of the talar dome: an anatomic pitfall of ankle MR imaging.
AB  - PURPOSE: To identify a normal groove in the posterior aspect of the talus as a
      potential pitfall in interpretation of ankle magnetic resonance (MR) images.
      MATERIALS AND METHODS: In 40 patients, T1-weighted spin-echo and T2-weighted fast
      spin-echo sagittal MR images were retrospectively reviewed from 47 consecutive
      routine ankle examinations. The patients were referred for evaluation of ligament
      and tendon abnormalities, such as tendinitis and tear, and suspected osseous and
      osteochondral injuries. Images were assessed for the presence of an erosion-like
      defect in the posterior aspect of the talar dome. Radiographs were available in
      13 cases. Sagittal T1-weighted spin-echo sequences were also performed in 14
      embalmed cadaveric ankles, followed by sectioning and dissection of three
      specimens. RESULTS: A defect was seen in 45 of 47 ankle MR imaging examinations.
      Radiographs did not show the defect. All 14 cadaveric ankles demonstrated the
      defect at MR imaging. At anatomic dissection, the defect was a normal groove for
      the passage of the posterior talofibular ligament. CONCLUSION: The pseudodefect
      of the talar dome is a normal groove for the posterior talofibular ligament and
      should not be misinterpreted as an articular erosion or osteochondral defect.

PMID- 9169717
TI  - Necrotizing fasciitis: CT characteristics.
AB  - PURPOSE: To establish computed tomographic (CT) criteria for the diagnosis of
      necrotizing fasciitis. MATERIALS AND METHODS: Twenty CT scans in 20 patients with
      pathologically proved necrotizing fasciitis were reviewed retrospectively for
      fascial thickening, fat infiltration, focal fluid collection, soft-tissue gas,
      muscle involvement, and intra-abdominal extension; the findings were correlated
      with clinical factors, including associated illnesses, disease site, treatment,
      and outcome. RESULTS: Average patient age was 57.8 years; there were 13 men and
      seven women. Four patients (20%) died. Asymmetric fascial thickening and fat
      stranding were seen in 16 patients (80%). Gas tracking along fascial planes was
      present in 11 patients (55%), and abscesses were found in seven patients (35%).
      Infection sites were scrotum (n = 6), a lower extremity (n = 4), perineum (n =
      4), neck (n = 2), back (n = 2), arm (n = 1), and abdomen (n = 1). Underlying
      illness (n = 17) was diabetes in 10 patients (50%), alcoholism in three (15%),
      chronic renal failure in two (10%), and drug abuse in two (10%). CONCLUSION: CT
      criteria of asymmetric fascial thickening and gas are valuable in assessing
      suspected necrotizing fasciitis. CT also can provide information on coexistent
      deep collections.

PMID- 9169718
TI  - Hodgkin and non-Hodgkin lymphoma: local-regional radiation therapy after bone
      marrow transplantation.
AB  - PURPOSE: To assess the acute toxicity and therapeutic effect of local-regional
      radiation therapy after bone marrow transplantation performed for lymphoma in
      resistant relapse. MATERIALS AND METHODS: Twenty-one patients with Hodgkin (n =
      12) or non-Hodgkin lymphoma (n = 9) underwent local-regional radiation therapy
      after bone marrow transplantation. Posttransplantation radiation was delivered to
      the dominant site of pretransplantation disease. Three patients with Hodgkin
      lymphoma and four with non-Hodgkin lymphoma underwent radiation therapy for
      posttransplantation recurrence. Total body irradiation was used in 10 patients.
      Mean radiation dose was lower in patients who underwent total body irradiation
      than in those who did not (P = .05). RESULTS: Nineteen of 21 patients completed
      local-regional therapy. Nonhematologic toxicity was mild in 20 patients.
      Hematologic toxicity was severe in five patients, four of whom began radiation
      therapy with low platelet counts. In-field disease progression occurred in six of
      15 patients with relapse, including four with disease progression at the start of
      radiation therapy. Median progression-free survival was 12 months in patients
      with Hodgkin lymphoma and 1 month in patients with non-Hodgkin lymphoma.
      CONCLUSION: Posttransplantation local-regional radiation therapy can be safely
      administered in patients with lymphoma. Severe hematologic toxicity is a concern,
      however, in patients with low platelet counts.

PMID- 9169719
TI  - Breast-conserving radiation therapy: potential of inverse planning with intensity
      modulation.
AB  - PURPOSE: To evaluate inverse planning with beam-intensity modulation in breast
      conserving radiation therapy. MATERIALS AND METHODS: A prototype inverse
      treatment-planning system was used in five patients with early-stage breast
      tumors. The prescription for the breast was 5,040 cGy in 180-cGy fractions, with
      the primary tumor site receiving 6,000 cGy in 214-cGy fractions. Isodose
      distributions from the prototype were compared section by section with those from
      conventional three-dimensional planning. RESULTS: The inverse planning system
      showed dose variation of 84%-98% to 111%-113% in the primary tumor site. For
      whole-breast irradiation, 95% of the target volume received at least 4,000 cGy.
      High-dose areas were adjacent to the primary site. Lower-dose areas were in the
      most medial part of the breast. Compared with the conventional system, target
      doses were similar. The volume of lung and heart that received high doses was
      smaller; however, larger lung and heart volumes received doses of less than 1,200
      cGy. CONCLUSION: Intensity modulation may accomplish "concomitant boost"
      treatment. Acceptable dose gradients are achieved in the target volumes, with
      lower volumes of high-dose treatment in normal tissue. Plans that required
      comprehensive nodal radiation, in particular, were improved relative to
      conventional plans. Optimization of the planning system is needed to minimize the
      lung and heart volumes that receive low-dose radiation.

PMID- 9169721
TI  - Memory artifact related to selenium-based digital radiography systems.
AB  - Digital images acquired on radiography systems with amorphous selenium detectors
      are susceptible to "memory artifacts" from prior x-ray exposures. In routine
      clinical use and in a laboratory experiment, artifacts appeared in chest
      radiographs until the selenium recovered from initial exposure. Memory artifacts
      were eliminated when 3 minutes or more elapsed between acquisition of a lateral
      chest radiograph and acquisition of the next radiograph.

PMID- 9169720
TI  - US extended-field-of-view imaging technology.
AB  - PURPOSE: To develop an ultrasound (US) extended-field-of-view scanning technique
      that combines the convenience of a real-time scanner with the spatial advantages
      of a static B-mode scanner and provides a panoramic image in real time without
      position sensors or cumbersome articulated arms. MATERIALS AND METHODS: An image
      registration-based position-sensing technique was used to track probe motion and
      reconstruct a large composite image during real-time scanning. The probe motion
      (translation and rotation) was estimated by combining multiple local motion
      vectors. This computationally intensive process required a special programmable
      image processor. RESULTS: Large, resolution-preserved composite images up to 60
      cm long were obtained. Measurement accuracy as determined with phantom
      experiments was better than 5%. The method could be applied to any probe or image
      format. CONCLUSION: In addition to providing a panoramic image to expand
      diagnostic capabilities, extended-field-of-view US provides a more easily
      interpretable image and is an effective cross-specialty communication tool.

PMID- 9169722
TI  - Cause of perimesencephalic hyperattenuation in cases of ruptured vertebrobasilar
      aneurysm.

PMID- 9169723
TI  - Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout
      mice.
AB  - The importance of antibody-mediated immunity in primary and secondary Chlamydia
      trachomatis genital tract infections was examined by using a definitive model of
      B-cell deficiency, the microMT/microMT gene knockout mouse. Vaginally infected B
      cell-deficient microMT/microMT mice developed a self-limiting primary infection
      that was indistinguishable from infection of control C57BL/6 mice. Sera and
      vaginal secretions from infected mice were analyzed for anti-Chlamydia
      antibodies. C57BL/6 mice produced high-titered serum anti-Chlamydia
      immunoglobulin G2a (IgG2a), IgG2b, and IgA antibodies, and vaginal washes
      contained predominately anti-Chlamydia IgA. Serum and vaginal washes from
      infected B-cell-deficient mice were negative for anti-Chlamydia antibody. T-cell
      proliferation and delayed-type hypersensitivity assays were used as measures of
      Chlamydia-specific cell-mediated immunity and were found to be comparable for
      C57BL/6 and B-cell-deficient mice. Seventy days following primary infection, mice
      were rechallenged to assess acquired immunity. B-cell-deficient mice which lack
      anti-Chlamydia antibodies were more susceptible to reinfection than
      immunocompetent C57BL/6 mice. However, acquired immune resistance was evident in
      both strains of mice and characterized by decreased shedding of chlamydiae and an
      infection of shorter duration. Thus, this study demonstrates that cell-mediated
      immune responses alone were capable of resolving chlamydial infection; however,
      in the absence of specific antibody, mice were more susceptible to reinfection.
      Therefore, these data suggest that both humoral and cell-mediated immune
      responses were important mediators of immune protection in this model, though
      cell-mediated immune responses appear to play a more dominant role.

PMID- 9169724
TI  - Functional analysis of Mycoplasma arthritidis-derived mitogen interactions with
      class II molecules.
AB  - The ability of superantigens (SAGs) to trigger various cellular events via major
      histocompatibility complex (MHC) class II molecules is largely mediated by their
      mode of interaction. Having two MHC class II binding sites, staphylococcal
      enterotoxin A (SEA) is able to dimerize MHC class II molecules on the cell
      surface and consequently induces cytokine gene expression in human monocytes. In
      contrast, cross-linking with specific monoclonal antibodies or T-cell receptor is
      required for staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin 1
      (TSST-1) to induce similar responses. In the present study, we report how
      Mycoplasma arthritidis-derived mitogen (MAM) may interact with MHC class II
      molecules to induce cytokine gene expression in human monocytes. The data
      presented indicate that MAM-induced cytokine gene expression in human monocytes
      is Zn2+ dependent. The MAM-induced response is completely abolished by
      pretreatment with SEA mutants that have lost their capacity to bind either the
      MHC class II alpha or beta chain, with wild-type SEB, or with wild-type TSST-1,
      suggesting that MAM induces cytokine gene expression most probably by inducing
      dimerization of class II molecules. In addition, it seems that SEA and MAM
      interact with the same or overlapping binding sites on the MHC class II beta
      chain and, on the other hand, that they bind to the alpha chain most probably
      through the regions that are involved in SEB and TSST-1 binding.

PMID- 9169725
TI  - Generation of a mouse tumor necrosis factor mutant with antiperitonitis and
      desensitization activities comparable to those of the wild type but with reduced
      systemic toxicity.
AB  - In this study, we investigated whether the recently identified lectin-like domain
      of tumor necrosis factor (TNF) is implicated in its biological activities on
      mammalian cells. To this end, a mouse TNF (mTNF) triple mutant, T104A-E106A-E109A
      mTNF (referred to hereafter as triple mTNF), lacking the lectin-like affinity of
      mTNF for specific oligosaccharides, was compared with the wild-type molecule for
      various TNF effects in vitro and in vivo. The triple mTNF displayed a 50-fold
      reduced TNF receptor 2 (TNFR2)-mediated bioactivity but only a 5-fold-reduced
      TNFR1-mediated bioactivity in vitro. The specific activity of the triple mutant
      on L929 fibrosarcoma cells was slightly reduced compared with that of the wild
      type. We subsequently assessed the systemic toxicity of triple versus wild-type
      mTNF, since TNFR2 is partially implicated in this activity. The triple mTNF had a
      significantly reduced toxicity compared with that of wild-type mTNF in vivo.
      Moreover, we compared the effects of the triple and the wild-type mTNFs in TNFR1
      mediated phenomena, such as (i) induction of tolerance towards a lethal mTNF dose
      and (ii) protective activity in cecal ligation and puncture-induced septic
      peritonitis. No significant differences between the mutant and wild-type forms
      were observed. In conclusion, these results indicate that triple mTNF, lacking
      TNF's lectin-like binding capacity, has reduced systemic toxicity but retains the
      tolerance-inducing and peritonitis-protective activities of wild-type mTNF.

PMID- 9169727
TI  - Toxicity and immunogenicity of a verotoxin 1 mutant with reduced
      globotriaosylceramide receptor binding in rabbits.
AB  - The verotoxins (VT1 and VT2), produced by strains of enterohemorrhagic
      Escherichia coli, have been implicated in the pathogenesis of hemorrhagic colitis
      and the hemolytic uremic syndrome. To better understand the role of
      globotriaosylceramide (Gb3) receptor binding by the verotoxins in disease
      production, we examined the clinicopathologic effects of an intravenously (i.v.)
      administered verotoxin 1 mutant holotoxin (Phe30Ala) in rabbits. The substitution
      of alanine for phenylalanine 30 in the VT1 B subunit has been shown previously to
      reduce both Gb3 binding affinity and capacity in vitro. This reduction in
      receptor binding corresponded to a 10(5)-fold reduction in the toxic activity of
      VT1 on a Vero cell monolayer. In this study, purified 125I-labeled Phe30Ala was
      administered i.v. to rabbits to determine its specific distribution in rabbit
      tissues. In contrast to the rapid elimination of i.v. administered 125I-VT1 from
      the bloodstream, 125I-Phe30Ala had a 52-fold-longer half-life in serum and failed
      to localize preferentially in the gastrointestinal tract and central nervous
      system (CNS). Rabbits challenged with Phe30Ala at a dose equivalent to 10 times
      the 50% lethal dose (LD50) of VT1 showed no visible clinical symptoms typical of
      VT effect after 7 days. Administration of Phe30Ala at a dose equivalent to 100
      times the LD50 of VT1, however, caused both clinical and histopathologic features
      indistinguishable from VT1 toxemia in rabbits, although the onset of symptoms was
      delayed. Rabbits were immunized with Phe30Ala and challenged i.v. with either
      125I-VT1 or 125I-VT2. The specific uptake of 125I-VT1 in the gastrointestinal
      tract and CNS was totally inhibited in Phe30Ala immune rabbits. Only a partial
      decrease in target organ uptake was observed in Phe30Ala immune rabbits
      challenged with 125I-VT2. From this study, we conclude that Gb3 binding is
      responsible for target organ localization of VT1 and disease production in the
      rabbit. The ability of Phe30Ala to induce both strong antibody and protective
      responses against VT1 suggests that VT mutants with reduced receptor binding
      properties may be useful in vaccine strategies. A further reduction in the
      toxicity of Phe30Ala would be required for its use as a natural toxoid to protect
      against human verotoxigenic E. coli infections.

PMID- 9169726
TI  - Distribution of drb genes coding for Dr binding adhesins among uropathogenic and
      fecal Escherichia coli isolates and identification of new subtypes.
AB  - The Dr family of related adherence structures, some fimbriated and others
      afimbriated, bind to decay-accelerating factor molecules on human cells. Dr is
      associated with recurring urinary tract infection (UTI), but the distribution of
      Dr subtypes among uropathogenic Escherichia coli causing UTI among otherwise
      healthy women has yet to be described. A total of 787 UTI and fecal E. coli
      isolates from college women were screened for the presence of Dr sequences (drb).
      Fifteen percent of UTI strains were drb positive, compared to 5% of fecal
      strains. The adhesin (E gene) subtype of each drb-positive strain was determined
      by type-specific PCR followed by restriction enzyme analysis. Among 78 drb
      positive strains, we found 14 (18%) afaE1, 1 (1.3%) afaE2, 1 (1.3%) afaE3, 9
      (12%) draE, 9 (12%) draE-afaE3 hybrid, 1 (1.3%) daaE, 32 (41%) afaE5, 4 (5.1%)
      F131 E gene-like, and 7 untypeable strains. All untypeable E genes were cloned
      and sequenced, revealing four additional new classes of E genes, including two
      similar to the previously identified nonfimbrial E series. While a great range of
      diversity exists among the E genes, restriction fragment length polymorphism
      analysis demonstrated that all of these drb operons share a highly conserved gene
      structure. The most common subtype, afaE5, occurred three times as often among
      UTI than fecal strains. Over half of the drb-positive strains and 80% of those
      positive for afaE5 have the same virulence signature (positive for aer, kpsMT,
      ompT, and fim), suggesting an association of this profile with UTI pathogenesis.

PMID- 9169728
TI  - A recombinant Bacillus anthracis strain producing the Clostridium perfringens Ib
      component induces protection against iota toxins.
AB  - The Bacillus anthracis toxinogenic Sterne strain is currently used as a live
      veterinary vaccine against anthrax. The capacity of a toxin-deficient derivative
      strain to produce a heterologous antigen by using the strong inducible promoter
      of the B. anthracis pag gene was investigated. The expression of the foreign gene
      ibp, encoding the Ib component of iota toxin from Clostridium perfringens, was
      analyzed. A pag-ibp fusion was introduced by allelic exchange into a toxin
      deficient Sterne strain, thereby replacing the wild-type pag gene. This
      recombinant strain, called BAIB, was stable and secreted large quantities of Ib
      protein in induced culture conditions. Mice given injections of live BAIB spores
      developed an antibody response specific to the Ib protein. The pag-ibp fusion was
      therefore functional both in vitro and in vivo. Moreover, the immunized animals
      were protected against a challenge with C. perfringens iota toxin or with the
      homologous Clostridium spiroforme toxin. The protective immunity was mediated by
      neutralizing antibodies. In conclusion, B. anthracis is promising for the
      development of live veterinary vaccines.

PMID- 9169729
TI  - Virulence properties and clonal structures of strains of Escherichia coli O119
      serotypes.
AB  - A total of 110 Escherichia coli strains of serogroup O119 were examined for the
      presence of virulence properties characteristic of enteropathogenic E. coli
      (EPEC). Three virulence patterns were distinguished based on the detection of a
      chromosomal gene mediating intimate attachment (eaeA) and plasmid DNA involved in
      localized adherence (EAF and bfpA). The first pattern, represented by strains
      which hybridized with three gene probes, was the most common (68%) and, with a
      single exception, included only O119:H6 strains. Of these strains, 90% showed a
      typical localized adherence (LA) pattern in HEp-2 cells and 96% were positive for
      intimate attachment in a fluorescent-actin staining test with a 3-h incubation
      period. The second pattern was represented by strains which hybridized with the
      eaeA gene only. Most (89.5%) of these strains showed the LA phenotype but only
      after 6 h of incubation (LA-like phenotype). The third pattern consisted of
      strains which were positive for eaeA and bfpA but did not hybridize with the EAF
      probe. Most (80%) of these strains exhibited the LA-like phenotype. Analysis of
      several eaeA+ bfpA+ strains for the expression of the pilin subunit (BfpA) of the
      bundle-forming pili demonstrated that all LA strains expressed BfpA whereas the
      LA-like strains did not. The study of the clonal relationships, carried out by
      multilocus enzyme electrophoresis in 79 representative strains, defined 11
      distinct electrophoretic types (ETs). ET1 included 66% of the strains, most of
      which displayed the eaeA+ bfpA+ EAF+ pattern and were serotyped as O119:H6 or
      O119:H-. The remaining 10 ETs were each represented by no more than five strains
      and, with the exception of ET8, included strains of a single serotype. The
      genetic relatedness of the ETs revealed two main clusters, with most strains in
      cluster A having the eaeA+ bfpA+ EAF+ combination and a O119:H6 serotype. Cluster
      B was represented by atypical EPEC strains with only the eaeA+ and the eaeA+
      bfpA+ virulence pattern.

PMID- 9169730
TI  - Genetic and transcriptional analysis of flgB flagellar operon constituents in the
      oral spirochete Treponema denticola and their heterologous expression in enteric
      bacteria.
AB  - Oral spirochetes possess many potential virulence factors, including the capacity
      for tissue invasion and persistence despite a vigorous host immune response. In
      an attempt to identify treponemal immunoreactive components, sera derived from
      individuals with advanced periodontal disease were used as a reagent to isolate
      recombinant bacteriophage lambda clones expressing antigens of the oral
      spirochete Treponema denticola ATCC 35405. Nucleotide sequence analysis of a
      clone expressing three immunoreactive products has revealed seven T. denticola
      genes which appear to encode homologs of flagellar basal body constituents, FlgB,
      FlgC, FliE, and FliF, a flagellar switch component, FliG, and the putative
      flagellar export proteins, FliH and FliI, initially characterized in Salmonella
      typhimurium. Also identified was a gene resembling fliJ. Primer extension
      analysis identified a transcriptional start site 5' to the treponemal flgB gene.
      Appropriately spaced with respect to this start site was a sigma28 binding motif.
      The absence of additional identifiable sigma factor binding motifs within the
      treponemal sequence and the proximity of adjacent genes suggested operonic
      arrangement, and reverse transcriptase PCR provided evidence of cotranscription.
      Supporting the identification of these genes as flagellar components,
      heterologous expression in enteric bacteria of the putative switch basal body
      genes from T. denticola interfered with motility. Specifically, the presence of a
      plasmid expressing treponemal fliG reduced swarming motility in S. typhimurium,
      while in Escherichia coli, this plasmid conferred a nonmotile phenotype and a
      reduction in flagellar number. Thus, while spirochetal flagella are subject to
      unique synthetic and functional constraints, the organization of flagellar genes
      and the presence of sigma28-like elements are reminiscent of the flagellar
      systems of other bacteria, and there appears to be sufficient conservation of
      constituent proteins to allow interaction between T. denticola switch-basal body
      proteins and the flagellar machinery of gram-negative bacteria.

PMID- 9169731
TI  - Characterization of an antigen from Leishmania amazonensis amastigotes able to
      elicit protective responses in a murine model.
AB  - Lymphoproliferative responses to an antigen from Leishmania amazonensis
      amastigotes with an apparent molecular mass of 30 kDa, termed p30, were evaluated
      with BALB/c mice. The p30 antigen was purified after separation of parasite
      extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by
      electroelution. Lymphoproliferative responses to p30 were obtained by
      subcutaneous immunization of animals with L. amazonensis amastigote extracts, and
      maximal stimulation indices were observed at an antigen concentration of 5
      microg/ml. Induction of lymphoproliferation by p30 is stage specific, and no
      differences in the responses to this antigen between mice susceptible and
      resistant to L. amazonensis were detected. The predominant T cells characterized
      in the lymphocyte cultures were CD4+. Lymphokine analysis of the supernatants
      from these cultures indicated that Th1 is the subset involved in the
      lymphoproliferative responses to the antigen. BALB/c mice immunized with p30 and
      challenged with L. amazonensis amastigotes showed a very low level of infection,
      indicating a protective role for p30 and a correlation between Th1 and
      protection. Further biochemical characterization studies showed that this antigen
      presents cysteine proteinase activity.

PMID- 9169732
TI  - Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27
      epitopes on human monocytes.
AB  - The expression of serologic HLA-B27 epitopes on leukocytes of patients with
      reactive arthritis or ankylosing spondylitis has been shown to be modified in the
      course of the disease. The purpose of this work was to study whether phagocytosis
      of arthritis-triggering microbes in vitro alters the expression of HLA-B27
      molecules on human antigen-presenting cells and to characterize the underlying
      mechanisms. Human monocytes and HLA-B27- or HLA-A2-transfected human U-937 cells
      were exposed to Yersinia enterocolitica serotype O:3. The expression of different
      epitopes of HLA-B27 was monitored by using immunofluorescence, and their
      synthesis was determined by quantitative immunoprecipitation. Our results show
      that phagocytosis of Y. enterocolitica serotype O:3 changed the expression of
      serological HLA-B27 epitopes. This was due to the reduced synthesis of HLA-B27
      molecules. The expression of especially the epitopes which depend on the presence
      of peptides in the antigen-binding groove was changed. The expression of the ME1
      epitope, which has been shown to be important for T-cell recognition in patients
      with reactive arthritis, was decreased. Down-regulation of epitopes important for
      the T-cell recognition may impair the elimination of arthritis-triggering
      microbes and lead to persistent infection. In addition, Y. enterocolitica
      serotype O:3 seemed to alter the repertoire of peptides presented by the HLA-B27
      molecules on human monocytes. This may have a role in the pathogenesis of
      reactive arthritis via an autoimmune mechanism.

PMID- 9169733
TI  - Reactivation of chlamydial genital tract infection in mice.
AB  - A model was developed to study chlamydial quiescence in C3H/HeN (C3H) and
      C57BL/6N (C57) mice following genital tract infection by Chlamydia trachomatis
      MoPn. Reactivation of chlamydial shedding following immunosuppression indicated
      that viable MoPn remained in the genital tract for up to 4 or 5 weeks after the
      apparent clearance of a primary infection. Either cyclophosphamide or cortisone
      acetate treatment could cause reactivation, but cyclophosphamide was more
      effective. However, the frequency of reactivation by either drug diminished with
      time in both mouse strains. Progesterone treatment prior to infection of C57 mice
      greatly reduced the frequency of reactivation by cyclophosphamide and also
      correlated with the development of marked fluid accumulation and distension of
      the uterine horns in the vast majority of those animals. This pathology was
      apparent by 5 to 7 weeks postinfection and was consistently seen through 110 days
      postinfection. Neither of these phenomena was observed in C57 mice that had not
      been treated with progesterone or in C3H mice under any conditions tested. The
      infecting dose of MoPn did not clearly influence the frequency of reactivation in
      either inbred strain as defined by this model.

PMID- 9169734
TI  - Induction of nitric oxide production by polyosides from the cell walls of
      Streptococcus mutans OMZ 175, a gram-positive bacterium, in the rat aorta.
AB  - The cardiovascular dysfunctions associated with septic shock induced by gram
      negative or gram-positive bacteria (gram-positive or gram-negative septic shock)
      are comparable. In gram-negative septic shock, lipopolysaccharide (LPS) induces
      nitric oxide (NO) synthase, which contributes to the vascular hypotension and
      hyporeactivity to vasoconstrictors. The role of NO in gram-positive septic shock
      and the nature of the bacterial wall components responsible for the vascular
      effects of gram-positive bacteria are not well known. This study investigated the
      vascular effects of cell wall serotype polyosides, rhamnose glucose polymers
      (RGPs), from Streptococcus mutans, in comparison with lipoteichoic acid (LTA)
      from Staphylococcus aureus, on the induction of NO synthase activity in the rat
      aorta. We show that 10 microg of both RGPs and LTA per ml induced hyporeactivity
      to noradrenaline, L-arginine-induced relaxation, increases of 2.2- and 7.8-fold,
      respectively, of cyclic GMP production, and increases of 7- and 12-fold in
      nitrite release. All of these effects appeared after several hours of incubation
      and were inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of NO synthase. Electron paramagnetic resonance spin trapping
      experiments demonstrated directly that RGPs and LTA induced NO overproduction
      (four- to eightfold, respectively) in rat aortic rings; this production was
      inhibited by L-NAME and prevented by dexamethasone. These results demonstrate
      directly the induction of NO production in vascular tissue by LTA and show that
      another, chemically different component of gram-positive bacteria can also have
      these properties. This result suggests that different components of the gram
      positive bacterial wall could be implicated in the genesis of cardiovascular
      dysfunctions observed in gram-positive septic shock.

PMID- 9169735
TI  - Intranasal immunization with C5a peptidase prevents nasopharyngeal colonization
      of mice by the group A Streptococcus.
AB  - Early inflammatory events are initiated by phased production of C5a and
      interleukin-8 in tissue. Most serotypes of group A streptococci express a surface
      bound peptidase (SCPA) which specifically cleaves mouse and human C5a
      chemotaxins. This study investigates the impact of SCPA on colonization of the
      nasopharyngeal mucosa of mice and evaluates its potential to induce protective
      immunity. Two strains, serotypes M6 and M49, which contain insertion and deletion
      mutations in the SCPA gene (scpA) and represent the two major subdivisions of
      group A streptococci, were characterized and compared in a mouse intranasal
      infection model. In this model, SCPA mutants were more rapidly cleared from the
      nasopharynges of inoculated mice compared with wild-type strains. A 2,908-bp
      fragment of scpA49 gene, obtained by PCR, was ligated to the expression vector
      pGEX-4T-1 and expressed in Escherichia coli. The affinity-purified deltaSCPA49
      protein proved to be highly immunogenic in mice and rabbits. Although the
      purified deltaSCPA49 immunogen lacked enzymatic activity, it induced high titers
      of rabbit antibodies which were able to neutralize peptidase activity associated
      with M1, M6, M12, and M49 streptococci in vitro. This result confirmed that
      antipeptidase antibodies lack serotype specificity. Intranasal immunization of
      mice with the deleted form of the SCPA49 protein stimulated significant levels of
      specific salivary secretory immunoglobulin A (IgA) and serum IgG antibodies and
      reduced the potential of wild-type M1, M2, M6, M11, and M49 streptococci to
      colonize. These experiments suggest a new approach to vaccine development for
      prevention of streptococcal pharyngitis.

PMID- 9169736
TI  - Synthesis and immunological properties of Vi and di-O-acetyl pectin protein
      conjugates with adipic acid dihydrazide as the linker.
AB  - The Vi capsular polysaccharide of Salmonella typhi, a licensed vaccine for
      typhoid fever in individuals > or = 5 years old, induces low and short-lived
      antibodies in children, and reinjection does not elicit booster responses at any
      age. Its immunogenicity was improved by binding Vi to proteins by using N
      succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a linker. Similar findings
      were observed with the structurally related, di-O-acetyl derivative of pectin
      [poly-alpha(1-->4)-D-GalpA] designated OAcP. Protein conjugates of Vi and OAcP
      were synthesized by carbodiimide-mediated synthesis with adipic acid dihydrazide
      (ADH) as the linker. Hydrazide groups were introduced into proteins (bovine serum
      albumin or recombinant Pseudomonas aeruginosa exoprotein A) by treatment with ADH
      and 1-ethyl-3(3-dimethylaminopropyl carbodiimide (EDC). The resultant adipic acid
      hydrazide derivatives (AH-proteins), containing 2.3 to 3.4% AH, had antigenic and
      physicochemical properties similar to those of the native proteins. The AH
      proteins were bound to Vi and OAcP by treatment with EDC. The immunogenicity of
      Vi or OAcP, alone or as protein conjugates, was evaluated in young outbred mice
      and guinea pigs by subcutaneous injection of 2.5 and 5.0 microg, respectively, of
      polysaccharide, and antibodies were measured by enzyme-linked immunosorbent
      assay. All conjugates were significantly more immunogenic than Vi or OAcP alone
      and induced booster responses with 5- to 25-fold increases of antibodies. Vi
      conjugates were significantly more immunogenic than their OAcP analogs. A
      carboxymethyl derivative of yeast beta-glucan enhanced the anti-Vi response
      elicited by an OAcP conjugate but had no effect on the immunogenicity of Vi or of
      OAcP alone. Vi and OAcP conjugates synthesized by this scheme will be evaluated
      clinically.

PMID- 9169737
TI  - Pelvic inflammatory disease isolates of Neisseria gonorrhoeae are distinguished
      by C1q-dependent virulence for newborn rats and by the sac-4 region.
AB  - The virulence mechanism of Neisseria gonorrhoeae in pelvic inflammatory disease
      (PID) is not well understood, and an objective diagnostic method to identify
      patients with PID is lacking. We investigated the hypothesis that development of
      PID was associated with a C1q-dependent virulence property of gonococcal strains.
      Recent development of a C1q-dependent experimental model of gonococcal infection
      (S. Nowicki, M. Martens, and B. Nowicki, Infect. Immun. 63:4790-4794, 1995)
      created an opportunity to evaluate this hypothesis in vivo. Therefore, the
      virulence of 32 clinical isolates (18 PID isolates and 14 local infection [LI]
      isolates) was evaluated in experimental rat pups. A serum bactericidal assay was
      used to characterize a gonococcal serum-resistant (ser(r)) phenotype. PCR primers
      designed to amplify a suitable-size gonococcal sac-4 DNA fragment (unique for
      serum-resistant donor JC1) were used to evaluate the association of serum
      resistant genotype sac-4 with two phenotypes: C1q-dependent virulence expressed
      in vivo and resistance to bactericidal activity of human serum expressed in
      vitro. Strains were also characterized by auxotyping and serotyping. Of 32
      gonococcal strains, 15 (46.7%) caused C1q-dependent bacteremia in rat pups and
      were sac-4 positive and ser(r). However, of the 15 isolates, 13 (87%) represented
      strains associated with human PID and 2 (13%) were associated with LI. None of
      the strains that were completely serum-sensitive (ser(s)) and sac-4 negative
      produced C1q-dependent bacteremia in rat pups, suggesting that both ser(r) and
      sac-4 were required for infection. The serum-resistant recombinant recipient of
      sac-4 produced C1q-dependent bacteremia in the rat model similarly to the serum
      resistant donor of sac-4; the serum-sensitive parent strain did not produce
      bacteremia. These data suggest that sac-4-mediated serum resistance conferred C1q
      dependent virulence and is a unique characteristic associated with PID. These
      newly identified features may contribute to the understanding of the pathogenic
      mechanism of PID-associated strains and open perspectives for establishing novel
      diagnostic methods.

PMID- 9169738
TI  - Temporal effect of tumor necrosis factor alpha on murine macrophages infected
      with Mycobacterium avium.
AB  - Members of the Mycobacterium avium complex are a family of bacteria that persist
      within macrophages in the face of an immune response. Elimination of these
      organisms is likely due to cytokine-induced macrophage activation. Because
      macrophage activation by tumor necrosis factor alpha (TNF-alpha) appears critical
      for killing of intracellular M. avium, early downregulation of TNF-alpha levels
      in infected macrophages has been suggested as a survival mechanism for virulent
      strains of M. avium. We examined the relationship between TNF-alpha and growth of
      M. avium strains of differing virulence, as measured by their ability to grow in
      murine bone marrow-derived macrophages. When exogenous TNF-alpha was added
      immediately following macrophage infection, significant growth inhibition of
      virulent M. avium strains was observed. If TNF-alpha addition was delayed by 24 h
      or more, growth inhibition was abrogated. To determine if early downregulation of
      TNF-alpha levels could explain the differential growth of virulent and avirulent
      strains, levels of TNF-alpha and prostaglandin E2 (PGE2), which has been shown to
      suppress TNF-alpha production in uninfected macrophages, were quantified over
      time. Upregulation of both TNF-alpha and PGE2, as measured by enzyme-linked
      immunosorbent assay, was evident by 6 h postinfection, indicating that the
      ability of M. avium to replicate in macrophages was not directly correlated with
      early downregulation of TNF-alpha production. However, TNF-alpha bioactivity, as
      measured by cytotoxicity, was significantly decreased in virulent M. avium
      strains at all time periods examined. Treatment of infected macrophages with
      gamma interferon immediately after infection resulted in significantly increased
      levels of nitric oxide but did not affect the growth of virulent M. avium
      strains. These results suggest that while significant levels of TNF-alpha are
      present in supernatants from all M. avium strains, levels of biologically active
      TNF-alpha are significantly reduced in supernatants from virulent M. avium
      strains. Preliminary results suggest that upregulation of the soluble p75 TNF
      receptor may be one mechanism by which TNF-alpha bioactivity reduction occurs.

PMID- 9169739
TI  - Comparison of alternative buffers for use with a new live oral cholera vaccine,
      Peru-15, in outpatient volunteers.
AB  - During development of Peru-15, a new live oral vaccine for cholera, the role of
      buffer needed to be evaluated. Generally, oral bacterial vaccines are acid labile
      and need to be administered by using a formulation which protects them from
      gastric acid. We compared three different buffers for use with Peru-15, including
      a standard bicarbonate-ascorbic acid buffer, Alka-Seltzer, and a new electrolyte
      rice buffer, CeraVacx. Saline served as the control. Thirty-nine healthy adult
      volunteers received Peru-15 (10(8) CFU) with one of the three buffers or saline
      in a double-masked study. The volunteers were monitored for symptoms for 7 days
      after the dose, serum was tested for antibody responses by vibriocidal antibody
      and immunoglobulin G antitoxin enzyme-linked immunosorbent assays, and stool
      samples were tested for excretion of the vaccine strain. Side effects were
      minimal in all groups. All 30 volunteers who took Peru-15 with a buffer showed
      significant rises in vibriocidal antibody titer. The magnitude of the rises was
      higher in the CeraVacx group than in the other two buffer groups. Four of nine
      volunteers who took the vaccine with saline also showed increased titers, but
      they were lower than those in any of the three buffer groups. Excretion of the
      vaccine strain was similar in the buffer groups, but excretion was not associated
      with the magnitude of the vibriocidal responses. Excretion of Peru-15 was not
      detected in the saline group. We conclude that buffer does amplify the
      serological response to Peru-15 and that CeraVacx may provide benefits not
      provided by other buffers.

PMID- 9169740
TI  - Construction and characterization of a live attenuated vaccine candidate against
      Shigella dysenteriae type 1.
AB  - Vaccine candidates against Shigella dysenteriae type 1, which is associated with
      the most severe cases of bacillary dysentery, were constructed. The rfp and rfb
      gene clusters, which code for S. dysenteriae 1 O antigen biosynthesis, were
      randomly integrated into either the chromosome or the virulence plasmid of the
      rough attenuated Shigella flexneri aroD strain SFL124-27 with a minitransposon
      carrying an arsenite resistance selection marker. The recombinant clones
      efficiently expressed the recombinant O antigen, exhibited a normal growth
      pattern, were able to invade and survive within eukaryotic cells to the same
      extent as the parental strain, and expressed the recombinant antigen within
      invaded cells. A clone was selected as the vaccine candidate, which was
      demonstrated to be immunogenic and safe in animal models, leading to 47% full
      protection and 53% partial protection against challenge with the wild-type
      strain.

PMID- 9169741
TI  - Keratinocyte proinflammatory responses to adherent and nonadherent group A
      streptococci.
AB  - The gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the
      causative agent of a wide variety of suppurative infections of cutaneous tissues.
      Previous analyses have demonstrated that the M protein of S. pyogenes is an
      adhesin that directs the attachment of the streptococcus to keratinocytes in the
      skin. In this study, we have examined keratinocyte function in response to S.
      pyogenes and found that adherent versus nonadherent streptococci promote distinct
      patterns of expression of several proinflammatory molecules and keratinocyte cell
      fate. When analyzed by a quantitative reverse transcriptase PCR method, infection
      of cultured HaCaT keratinocytes with adherent, but not nonadherent, streptococci
      resulted in increased expression of mRNA for the cytokines interleukin-1alpha (IL
      1alpha), IL-1beta, and IL-8 but neither infection induced expression of tumor
      necrosis factor alpha. In contrast, both adherent and nonadherent S. pyogenes
      induced expression of IL-6 and each promoted synthesis and release of
      prostaglandin E2 (PGE2). However, considerably greater levels of IL-6 expression
      were stimulated by adherent streptococci relative to nonadherent streptococci and
      the kinetics of PGE2 release in response to nonadherent streptococci was delayed
      compared to the response to adherent streptococci. Staining with the fluorescent
      probe ethidium homodimer-1 revealed that keratinocyte membranes were rapidly
      damaged upon infection with adherent streptococci but were not damaged by
      nonadherent streptococci. Finally, treatments which inhibited streptococcal
      metabolism completely blocked the ability of adherent streptococci to elicit
      responses. These data suggest that expression of an adhesin is a strategy used by
      S. pyogenes to modulate keratinocyte responses during infection of the skin and
      implicate additional streptococcal products in these signaling interactions.

PMID- 9169742
TI  - Coexpression of the B subunit of Shiga toxin 1 and EaeA from enterohemorrhagic
      Escherichia coli in Vibrio cholerae vaccine strains.
AB  - A promoterless gene for the Shiga toxin 1 B subunit (stxB1) has been placed under
      transcriptional control of the Vibrio cholerae heat shock gene htpG. A
      chromosomal enterohemorrhagic Escherichia coli fragment containing eaeA and 400
      bp of upstream DNA was added to the construct, downstream of stxB1; no
      transcription terminators were located between the two genes. The plasmid
      construct was confirmed by DNA sequencing; in vitro transcription-translation
      studies demonstrated expression of EaeA from the plasmid. The htpGp-->stxB1, eaeA
      construct was inserted into lacZ on the chromosome of Peru2, an El Tor V.
      cholerae strain with both attRS1 sequences and the entire cholera toxin genetic
      element deleted, and into lacZ in JRB10, a Peru2 derivative that has a second
      copy of htpGp-->stxB1 also inserted in the V. cholerae virulence gene irgA. Two
      plasmid constructs, one containing stxB1 under the control of the tac promoter
      and another containing htpGp-->stxB1,eaeA, were transformed into Peru2.
      Expression of StxB1 by these constructs was quantified by enzyme-linked
      immunosorbent assay and was highest in the plasmid construct with stxB1 under the
      control of the tac promoter. Localization of EaeA to the outer membrane of the
      vector strains was demonstrated both by Western blotting and by
      immunofluorescence with an anti-EaeA antibody. A rabbit model for colonization by
      V. cholerae was used to compare the immune responses to the two heterologous
      antigens, StxB1 and EaeA, expressed by these strains. Rabbits immunized with
      Peru2 transformed with a plasmid carrying tac-->stxB1 developed neutralizing
      serum anti-StxB1 immunoglobulin G antibody responses. One of two rabbits
      immunized with a strain carrying a chromosomal copy of eaeA developed a marked
      immune response against EaeA. The plasmid construct containing htpGp-->stxB1,eaeA
      was unstable, producing low levels of StxB1 in vitro and not evoking anti-EaeA
      antibody responses in vivo following oral immunization. Chromosomal insertion of
      eaeA may be preferred for future expression of this antigen in V. cholerae
      vaccine constructs.

PMID- 9169743
TI  - Effects of adenosine on the functions of circulating polymorphonuclear leukocytes
      during hyperdynamic endotoxemia.
AB  - Endotoxin-activated polymorphonuclear leukocytes (PMNL) adhere to the vascular
      endothelium and cause damage by the release of toxic superoxide anions (O2-).
      Because adenosine is a potent inhibitor of PMNL in vitro, the present study
      investigates the effects of this nucleoside on the functions of circulating PMNL
      in a standardized porcine model of hyperdynamic endotoxemia. Ten anesthesized
      pigs received an intravenous (i.v.) 330-min infusion of endotoxin (5 microg/kg of
      body weight per h). Another 10 pigs were also infused with endotoxin plus
      adenosine (150 microg/kg/min [i.v.]); this treatment was begun 30 min prior to
      the beginning of endotoxin treatment. Control groups (five animals per group)
      received either adenosine or physiological saline. Infusion of endotoxin caused
      severe neutropenia, shedding of L-selectin, upregulation of beta2-integrins,
      increased binding of C3-coated zymosan particles, and subsequent phagocytosis by
      PMNL. While phagocytosis-induced production of oxygen radicals appeared to
      decrease, extracellular release of superoxide anions was strongly enhanced.
      Infusion of adenosine during endotoxemia had no effect on neutropenia, expression
      of adhesion molecules, C3-induced adhesion, phagocytosis, or intracellular
      production of oxygen radicals, whereas extracellular release of O2- was strongly
      inhibited. Thus, i.v. infusion of adenosine during endotoxemia could be useful in
      protecting from O2(-)-mediated tissue injury without compromising the
      bactericidal mechanisms of PMNL.

PMID- 9169744
TI  - Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma
      interferon gene knockout mice.
AB  - Mice (C57BL/6), treated with progesterone and infected intravaginally with the
      mouse pneumonitis strain of Chlamydia trachomatis (MoPn), acquired genital tract
      disease that ascended from the endocervix to the uterine horns, oviducts, and
      ovaries in a temporal fashion before the occurrence of spontaneous
      microbiological resolution by about 28 days after infection. Surprisingly,
      dissemination of MoPn in small numbers to draining lymph nodes, the peritoneal
      cavity, spleen, liver, kidneys, and lungs occurred in normal mice during the
      early stages of disease (7 to 14 days) in a portion of infected animals but
      resolved from these tissues, by microbiological criteria, prior to resolution of
      genital tract involvement. In contrast, gamma interferon knockout (IFN-gamma KO)
      mice exhibited dissemination of infection to a greater extent and for longer
      periods in a variety of tissues, and a portion of infected IFN-gamma KO mice
      failed to microbiologically resolve their genital tract disease. By comparison,
      C57BL/6 SCID mice uniformly failed to resolve their genital tract disease and
      exhibited high levels of dissemination to all tissues tested for extended (50
      day) periods of times. Interestingly, although IFN-gamma KO mice failed to
      completely clear organisms from their genital tracts, they exhibited an
      attenuated infection indistinguishable from that of heterozygous littermates when
      challenged 112 days after primary infection. These data support a role for IFN
      gamma in containing dissemination of MoPn from the genital tract to extragenital
      sites and in the microbiological resolution of infection. Data also indicate that
      IFN-gamma is not required for modulating reinfections, which normally follow a
      shorter and less dramatic course.

PMID- 9169745
TI  - Characteristics and prevalence within serogroup O4 of a J96-like clonal group of
      uropathogenic Escherichia coli O4:H5 containing the class I and class III alleles
      of papG.
AB  - The recent discovery of a geographically dispersed clonal group of Escherichia
      coli O4:H5 that includes prototypic uropathogenic strain J96 prompted us to
      determine the prevalence of J96-like strains within serogroup O4 and to further
      assess the characteristics of such strains. We used O:K:H;F serotyping, PCR-based
      genomic fingerprinting, pulsed-field gel electrophoresis (PFGE), multilocus
      enzyme electrophoresis (MLEE), and PCR detection of the three papG alleles and of
      the cytotoxic necrotizing factor 1 (cnf1) and aerobactin (aer) gene sequences to
      characterize the 15 O4 strains among 336 E. coli isolates from three clinical
      collections (187 from mixed-source bacteremia, 75 from urosepsis, and 74 from
      acute cystitis). J96-like strains constituted approximately half of the O4
      strains, or 2% of the total population. In contrast to other O4 strains, the J96
      like strains characteristically exhibited specific group III capsular antigens,
      the H5 flagellar and F13 fimbrial antigens, a distinctive PCR genomic
      fingerprint, the class III papG allele (plus, in 50% of strains, the enigmatic
      class I papG allele), and cnf1 but lacked aer. A subset of these strains was
      remarkably homogeneous with respect to all these characteristics and exhibited a
      distinctive PFGE fingerprint and MLEE pattern. These findings clarify the
      epidemiological relevance of J96 as a model extraintestinal pathogen, provide
      further evidence of the class I papG allele outside of strain J96, and offer
      insights into the evolution of E. coli serogroup O4.

PMID- 9169747
TI  - Vaccine- and antigen-dependent type 1 and type 2 cytokine induction after primary
      vaccination of infants with whole-cell or acellular pertussis vaccines.
AB  - Cytokine profiles were examined 1 month after primary vaccination of infants with
      a whole-cell pertussis vaccine (wP) (Connaught) or either of two acellular
      pertussis vaccines, aP-Chiron Biocine (aP-CB) or aP-SmithKline Beecham (aP-SB),
      each combined with diphtheria-tetanus toxoids (DT), in Bordetella pertussis
      antigen-stimulated or unstimulated peripheral blood mononuclear cells (PBMC).
      Pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were
      used as antigens, and the children were defined as responsive when their PBMC
      proliferated in response to these antigens. The controls were either children who
      received only DT or children who received pertussis vaccine but whose PBMC did
      not proliferate upon stimulation with B. pertussis antigens (unresponsive
      children). Antigen-stimulated PBMC of responsive wP recipients were characterized
      by an elevated production of T-helper-cell type 1 cytokines gamma interferon (IFN
      gamma) and interleukin 2 (IL-2), low to minimal production of IL-5, and no
      production of IL-4. The PBMC of aP vaccine-responsive recipients showed, in
      addition to the elevated IFN-gamma production, a consistent, antigen-dependent
      production of type 2 cytokines (IL-4 and IL-5), with PRN being the most and PT
      being the least effective antigen. Type 2 cytokine induction was more pronounced
      in aP-SB than in aP-CB recipients, as shown by the presence of IL-4 mRNA
      transcripts and higher IL-5 production in the former (161.6 +/- 36 and 47.9 +/-
      44 pg/ml [mean +/- standard error for five subjects each], respectively, after
      PRN stimulation). Appreciable, antigen-unstimulated (constitutive) IFN-gamma
      production was also detected in PBMC cultures of all vaccinees. However, this
      spontaneous IFN-gamma production was, in most vaccinees, significantly lower than
      the antigen-driven cytokine production. In contrast, no constitutive type 2
      cytokine production was ever observed in any vaccine group. PBMC from the two
      control groups (either DT or pertussis vaccine recipients) did not show any type
      2 cytokine production, while IFN-gamma production was comparable in both antigen
      stimulated and unstimulated conditions. Absence of type 2 cytokines and low
      levels of constitutive IFN-gamma production were also seen in prevaccination
      children. Thus, pertussis vaccines induce in infants a basically type 1 cytokine
      profile, which is, however, accompanied by some production of type 2 cytokines.
      The latter are more expressed by aP-SB than by aP-CB recipients, and with PRN
      than with other antigens, and they are minimally expressed in wP recipients and
      with PT as antigen. Our data also highlight a constitutive IFN-gamma production
      in infancy, which might reflect natural immunization and/or the burden of
      concomitant vaccinations and which may have an impact on T-helper-cell cytokine
      pattern polarization consequent to pertussis vaccination.

PMID- 9169746
TI  - Effect of anticoagulants on binding and neutralization of lipopolysaccharide by
      the peptide immunoglobulin conjugate CAP18(106-138)-immunoglobulin G in whole
      blood.
AB  - The 18-kDa cationic protein CAP18 is an antimicrobial protein isolated from
      rabbit granulocytes that binds lipopolysaccharide (LPS) and inhibits many of its
      biological activities. We covalently coupled a synthetic peptide representing
      amino acids 106 to 138 of CAP18 to human immunoglobulin G (IgG) by using the
      heterobifunctional linker N-succinimidyl-3-(2-pyridyidithio)propionate. The
      ability of CAP18(106-138)-IgG to bind and neutralize LPS in whole blood in the
      presence and absence of anticoagulants was studied. Both CAP18(106-138) and
      CAP18(106-138)-IgG significantly suppressed LPS-induced tumor necrosis factor
      (TNF) production in whole blood in the absence of anticoagulants. EDTA
      potentiated the ability of CAP18(106-138) and CAP18(106-138)-IgG to decrease LPS
      induced TNF production in a dose-dependent manner. In contrast, heparin inhibited
      the ability of CAP18(106-138) and CAP18(106-138)-IgG to suppress LPS-induced TNF
      production. EDTA also enhanced LPS capture in a fluid-phase binding assay that
      utilizes magnetic anti-IgG beads to capture CAP18(106-138)-IgG (and bound
      [3H]LPS) in whole blood. In contrast, heparin inhibited the binding dose
      dependently. We conclude that CAP18(106-138)-IgG binds to and neutralizes LPS in
      whole blood in the absence of anticoagulants. Further studies of its protective
      efficacy in animal models are warranted. Caution should be used in interpreting
      assays that measure the binding and neutralization of LPS in whole blood in the
      presence of calcium-binding anticoagulants or heparin.

PMID- 9169748
TI  - Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes
      produces a Th1-like cytokine response associated with fibrosis and scarring.
AB  - Chlamydia trachomatis-associated female infertility and ectopic pregnancy are
      caused by postinflammatory fibrosis and scarring of the upper genital tract.
      Scarring of the upper genital tract is associated with multiple infectious
      episodes with C. trachomatis. To study the immune response that occurs with
      multiple infections of C. trachomatis in the female upper genital tract, a Macaca
      nemestrina model was used. Subcutaneous pockets containing autologous salpingeal
      tissue implants were inoculated three times with C. trachomatis. The inflammation
      after three inoculations was associated with a mononuclear infiltrate dominated
      by CD8 T-cell lymphocytes. Perforin mRNA was induced in infected pockets,
      demonstrating that activated cytolytic lymphocytes were present in the lesions.
      Fibrosis, as evidenced by fibroblast proliferation and connective tissue
      deposition, was observed by the third infection. Cytokine mRNAs induced by
      repeated chlamydial infection included gamma interferon, interleukin-2 (IL-2), IL
      6, and IL-10 mRNAs, but IL-4 mRNA was not induced. Nearly identical findings were
      found in macaque fallopian tubes infected in situ repeatedly with C. trachomatis,
      validating the subcutaneous pocket model of chlamydial salpingitis. However, it
      was not possible to evaluate if there was an induction of perforin mRNA in
      infected salpingeal tubes in situ, because there was a high basal level of
      perforin mRNA in these tissues. These results suggest that repeated chlamydial
      infection of the female upper genital tract leads to CD8 T-cell predominance, a
      Th1-like cytokine milieu, and these inflammatory changes are associated with
      progression to fibrosis associated with female infertility.

PMID- 9169749
TI  - Identification of proteins of Francisella tularensis induced during growth in
      macrophages and cloning of the gene encoding a prominently induced 23-kilodalton
      protein.
AB  - The adaptation of facultative intracellular bacteria to host macrophages involves
      regulation of the synthesis of bacterial proteins. We analyzed the protein
      synthesis of Francisella tularensis LVS growing intracellularly in the macrophage
      like murine cell line J774 and extracellularly in culture medium. After pulse
      labeling with [35S] methionine and separation by one- and two-dimensional
      polyacrylamide gel electrophoresis, induction of a few proteins during
      intracellular growth was demonstrated. One of them, a 23-kDa protein, was
      prominently induced in the macrophages and also when extracellularly growing F.
      tularensis was exposed to hydrogen peroxide. After isolation of the 23-kDa
      protein from a preparative two-dimensional gel, a 22-amino-acid N-terminal
      peptide and two peptides obtained by trypsin digestion were sequenced. Based on
      the sequences, degenerate oligonucleotides were constructed for use as primers in
      a PCR. Hybridization of amplified DNA to XbaI-digested LVS DNA identified the
      gene of the 23-kDa protein in a 1.3-kb DNA fragment. Nucleotide sequence analysis
      revealed an open reading frame encoding a putative protein of a calculated
      molecular mass of 22.2 kDa. The open reading frame was preceded by a sequence
      typical of ribosome-binding sites in Escherichia coli. The amplified gene was
      successfully expressed by the pTrc99A vector in E. coli under control of the trc
      promoter. The gene product showed the same mobility and immunoreactivity as the
      23-kDa protein of F. tularensis. The deduced amino acid sequence showed no
      significant homology with protein sequences in current data banks. Thus,
      intracellular growth of F. tularensis in macrophages was associated with
      prominent upregulation of a novel 23-kDa protein.

PMID- 9169750
TI  - The Yersinia enterocolitica GsrA stress protein, involved in intracellular
      survival, is induced by macrophage phagocytosis.
AB  - The Yersinia enterocolitica gsrA gene is a stress protein gene which was
      originally identified as essential for protecting cells under both extracellular
      environmental stress and intracellular stress in macrophages due to phagocytosis.
      The gsrA gene was shown to be a member of the htrA class of genes and to possess
      a sequence homologous to that of the promoter recognized by a stress-induced
      sigma factor, sigmaE. In order to study the induction of the potentially sigmaE
      controlled gsrA gene in Y. enterocolitica after phagocytosis by macrophages, we
      identified GsrA by overproducing the protein using a T7 promoter-gsrA fusion. We
      found that it is translated as an unstable 49,500-Da protein which is processed
      by removal of an amino acid fragment consisting of 27 residues, resulting in a
      stable 46,800-Da protein. By radiolabeling proteins specific to bacteria in the
      J774-1 macrophage-like cell line, we found that the production of GsrA protein is
      indeed enhanced in bacterial cells growing within macrophage phagosomes.
      Transcriptional activation of the gsrA gene was determined by using the gsrA
      promoter-lacZ fusion system. This work provides the first piece of evidence that
      the sigmaE regulon responds to the stressful environment found in macrophages.

PMID- 9169751
TI  - Preferential recognition of human myocardial antigens by T lymphocytes from
      rheumatic heart disease patients.
AB  - Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune
      sequelae of upper respiratory infections with group A streptococci (GAS). To gain
      a better understanding of the pathogenesis of these diseases, we examined the in
      vitro proliferative responses of peripheral blood mononuclear cells (PBMC) from
      RHD patients to human myocardial proteins in a T-cell Western assay. A number of
      myocardial proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis were recognized by PBMC from both patients and controls. However,
      PBMC from a significant percentage of RHD patients (40%) responded to a discrete
      band of myocardial proteins migrating with an apparent molecular mass of 50 to 54
      kDa while none of the control subject PBMC responded to this protein band (P < or
      = 0.0001). To further investigate the link between infections with GAS and
      autoimmune carditis, we studied the proliferative responses of PBMC from patients
      and controls to myocardial proteins before and after in vitro stimulation of the
      cells with opsonized GAS isolated from ARF patients. Priming of PBMC with
      rheumatogenic GAS caused the percentage of RHD patients responding to the 50- to
      54-kDa myocardial proteins to increase from 43 to 90% (P < or = 0.0284). By
      contrast, PBMC from control subjects failed to recognize the 50- to 54-kDa
      myocardial proteins even after stimulation with the opsonized streptococci (P <
      or = 0.0001). The assay sensitivity was increased from 40 to 90% after priming of
      a patient's cells with opsonized GAS, but the positive predictive value was 100%
      in both unprimed and primed cultures. Antibodies generated to partially purified
      50- to 54-kDa myocardial proteins did not cross-react with either streptococcal
      homogenates, purified M protein, myosin, laminin, or vimentin, suggesting a lack
      of cross-reactivity at the humoral level. This study suggests that the 50- to 54
      kDa myocardial proteins contain a putative antigen that is preferentially
      recognized by T cells from RHD patients and demonstrates that exposure to
      streptococcal antigens enhances the ability of patients to recognize these
      proteins.

PMID- 9169752
TI  - Temperature-sensitive mutants of Actinobacillus pleuropneumoniae induce
      protection in mice.
AB  - Temperature-sensitive mutants of Actinobacillus pleuropneumoniae 4074, serotype
      1, were isolated after treatment with nitrosoguanidine and enrichment with
      penicillin and D-cycloserine. Of the four temperature-sensitive mutants evaluated
      in mice, one (A-1) had a tight phenotype (i.e., it ceased replication immediately
      after transfer to the nonpermissive temperature [37 degrees C]) and three (1-2, 4
      1, and 12-1) were coasters that continued replication for up to three generations
      after transfer to 37 degrees C. The reversion frequencies ranged from 10(-6) to
      10(-9), and cutoff temperatures ranged from 33 to 35 degrees C. No major changes
      were detected in the biochemical profiles; agglutination reactions;
      electrophoretic profiles of the lipopolysaccharides, outer membrane proteins, and
      hemolysin proteins; hemolytic titers; or CAMP factor reactions of the mutants and
      the wild-type bacteria. Groups of 3- to 5-week-old, female ICR mice were
      immunized intranasally with three doses of 3.5 x 10(6) CFU of the mutants over 3
      weeks and subsequently challenged intranasally with 5 50% lethal doses of the
      parental wild-type. Protection was induced by both the tight and the coaster
      mutants, with the 4-1 and 12-1 coasters eliciting greater protection (67 and 82%,
      respectively) than that induced by the A-1 tight mutant (57%). Intranasal
      immunization with both phenotypes induced serum antibody responses against the
      surface antigens and the hemolysin protein.

PMID- 9169753
TI  - A third secreted protein that is encoded by the enteropathogenic Escherichia coli
      pathogenicity island is required for transduction of signals and for attaching
      and effacing activities in host cells.
AB  - Enteropathogenic Escherichia coli strains are able to signal host cells, cause
      dramatic cytoskeletal rearrangements, and adhere intimately to the cell surface
      in a process known as the attaching and effacing effect. A pathogenicity island
      of 35 kb known as the locus of enterocyte effacement (LEE) is necessary and
      sufficient for this effect. The LEE encodes an outer membrane adhesin called
      intimin, a type III secretion apparatus, and the EspA and EspB secreted proteins.
      The DNA sequence of the region between espA and espB revealed a new gene, espD.
      The product of espD was demonstrated by using a T7 expression system. We
      constructed a nonpolar mutation in espD and found that the mutant is incapable of
      the signal transduction events that lead to activation of the putative intimin
      receptor in host cells and that the mutant fails to induce the attaching and
      effacing effect. These phenotypes were restored to the mutant by complementation
      with a plasmid containing the cloned espD locus. We demonstrated by
      immunoblotting and microsequencing that the EspD protein is secreted via the type
      III apparatus. Thus, we describe a novel locus encoding a secreted protein that
      is required for attaching and effacing activity.

PMID- 9169754
TI  - Pleiotropic effects of a mutation in rfaC on Escherichia coli hemolysin.
AB  - Several genes involved in the lipopolysaccharide (LPS) biosynthetic pathway have
      been shown to affect the expression or activity of Escherichia coli hemolysin
      (Hly), a secreted cytotoxin that is the prototype of the RTX family of toxins. To
      further study this relationship, E. coli K-12 strains harboring mutations in the
      LPS biosynthetic genes rfaS, rfaQ, rfaJ, rfaP, and rfaC were transformed with a
      recombinant plasmid harboring the hlyCABD operon and examined for their effects
      on extracellular expression and hemolytic activity. A mutation in rfaC that
      affected both extracellular expression and activity of Hly was studied in greater
      detail. This mutation led to a growth-phase-dependent decrease up to 16-fold in
      the steady-state level of extracellular HlyA, although transcription and
      secretion of HlyA were decreased no more than 2-fold. Specific hemolytic activity
      in toxin produced from the rfaC mutant strain was significantly reduced, in a
      growth-phase-dependent manner. With the rfaC gene supplied in trans, both the
      decreased expression and activity of Hly were restored to wild-type levels. Hly
      from the rfaC mutant strain exhibited much slower kinetics of hemolysis, a more
      rapid rate of decay of activity, and greater formation of apparently inactive
      HlyA-containing aggregates in culture supernatants than was exhibited in the wild
      type strain. A model is proposed for a physical interaction between LPS and Hly
      in which LPS with intact inner core participates in forming or maintaining an
      active conformation of Hly and helps to protect it from aggregation or
      degradation.

PMID- 9169756
TI  - Prelytic and lytic conformations of erythrocyte-associated Escherichia coli
      hemolysin.
AB  - Flow cytometry was developed as a method to assess the conformation of
      erythrocyte-bound Escherichia coli hemolysin polypeptide (HlyA). Topology of
      membrane-associated hemolysin (HlyA(E)) was investigated by testing surface
      accessibility of HlyA regions in lytic and nonlytic bound states, using a panel
      of 12 anti-HlyA monoclonal antibodies (MAbs). Hemolysin associates nonlytically
      with erythrocytes at 0 to 2 degrees C. To test the hypothesis that the nonlytic
      HlyA(E) conformation at 0 to 2 degrees C differs from the lytic conformation at
      23 degrees C, MAb epitope reactivity profiles at the two temperatures were
      compared by flow cytometry. Four MAbs have distinctly increased reactivity at 0
      to 2 degrees C compared to 23 degrees C. HlyA requires HlyC-dependent acylation
      at lysine residues 563 and 689 for lytic function. Toxin with cysteine
      substitution mutations at each lysine (HlyA(K563C) and HlyA(K689C)) as well as
      the nonacylated form of hemolysin made in a HlyC-deficient strain were examined
      by flow cytometry at 0 to 2 and 23 degrees C. The three mutants bind erythrocytes
      at wild-type toxin levels, but there are conformational changes reflected by
      altered MAb epitope accessibility for six of the MAbs. To test further the
      surface accessibility of regions in the vicinity of MAb-reactive epitopes,
      HlyA(E) was proteolytically treated prior to testing for MAb reactivity.
      Differences in protease susceptibility at 0 to 2 degrees and 23 degrees C for the
      reactivities of three of the MAbs further support the model of two distinct
      conformations of cell-associated toxin.

PMID- 9169755
TI  - Expression of botulinum toxin binding sites in Xenopus oocytes.
AB  - The binding of iodinated botulinum toxin type B to nerve membranes was studied by
      using rat and mouse preparations. The toxin was examined both in the single-chain
      and in the proteolytically processed dichain form, and binding sites both in the
      spinal cord and in various brain regions were assayed. Rat and mouse brains
      possessed specific binding sites for botulinum toxin type B. The average Kd
      values for the various rat and mouse membrane preparations examined were 4.2 +/-
      0.7 nM and 3.7 +/- 0.9 nM, respectively. The average Bmax values for the same
      tissue preparations were 7.3 +/- 0.7 pmol/mg of protein and 7.5 +/- 1.9 pmol/mg
      protein, respectively. The binding of botulinum toxin type B to rat brain
      membranes was not antagonized by a polyclonal antibody against the cytosolic
      domain of synaptotagmin 1 or by a monoclonal antibody directed against the
      luminal domain of synaptotagmin 1. In addition, these antibodies did not protect
      the mouse phrenic nerve-hemidiaphragm from toxin-induced neuromuscular blockade.
      Extraction of whole-brain mRNA and injection into Xenopus oocytes led to
      expression of binding sites for botulinum toxin. Extraction and injection of
      cerebellar mRNA led to expression of a higher density of binding sites. The
      number of binding sites was not diminished when oocytes were pretreated with
      antibodies against the cytosolic and luminal domains of synaptotagmin 1. These
      findings are likely to aid in the isolation, characterization, and reconstitution
      of toxin binding sites.

PMID- 9169758
TI  - Regulation of protein A synthesis by the sar and agr loci of Staphylococcus
      aureus.
AB  - The synthesis of protein A in Staphylococcus aureus is regulated by global
      regulatory loci such as sar and agr. Phenotypic data indicate that both sar and
      agr suppress protein A synthesis; like agr, sar also regulates protein A
      production at the transcriptional level. To determine the genetic requirement of
      sar in protein A suppression, we transformed shuttle plasmids containing various
      sar fragments into a sar mutant. Our results indicated that the 560-bp sarA
      transcript, or, more probably, the SarA protein (13.5 kDa), is sufficient for
      suppressing protein A gene transcription when introduced on a multicopy plasmid
      or as a single copy in the chromosome. Immunoblot analysis with a chicken anti
      protein A antibody also confirmed the reduction in protein A expression in these
      sar mutant clones. Complementation studies revealed that the transcription of the
      protein A gene can be suppressed in a sar mutant background by a plasmid
      containing RNAIII. Surprisingly, in agr deletion mutant clones and in clones
      derived from the agr-sar double mutant, protein A gene transcription can also be
      suppressed by plasmids containing the sarA transcript plus additional upstream
      sequence but not the sarA transcript alone. These data suggest that the sar locus
      can down-modulate protein A gene transcription via both RNAIII-dependent and
      RNAIII-independent pathways. Consistent with the hypothesis of an RNAIII
      independent pathway is an additional genetic requirement for protein A
      suppression in the agr deletion mutant RN6911 as well as the isogenic double sar
      agr mutant, whereas in the sar mutant background, the sarA transcript encoding
      the SarA protein alone is sufficient. These data suggested that both sar and agr
      are coregulators of protein A synthesis in S. aureus.

PMID- 9169757
TI  - Elevation of vacuolar pH inhibits the cytotoxic activity of furin-cleaved
      exotoxin A.
AB  - Exotoxin A (ETA) inhibits protein synthesis in cells by a process that involves
      receptor-mediated endocytosis and the transport of a 37-kDa proteolytic fragment
      across a membrane into the cytoplasm. The fragment is apparently generated by the
      endoprotease furin after the toxin has been endocytosed. Cleavage of ETA by furin
      requires a low pH in vitro, and presumably also in vivo. Drugs that raise the pH
      of intracellular compartments are known to protect cells from ETA. The simplest
      hypothesis to explain this protection has been that the drugs interfere with
      furin cleavage. To test this idea, we measured the effect of pH-elevating drugs
      on the action of ETA that had been precleaved with recombinant furin before
      addition to cells. Surprisingly, we found that pH-elevating drugs protected cells
      from precleaved ETA as well as intact ETA. These results suggest that the process
      by which ETA intoxicates cells requires a low vacuolar pH for another event in
      addition to proteolysis by furin.

PMID- 9169759
TI  - Evidence of genetic susceptibility to Chlamydia trachomatis-induced pelvic
      inflammatory disease in the pig-tailed macaque.
AB  - The macaque model of chlamydial pelvic inflammatory disease (PID) demonstrates
      individual variability in the time of onset of intrapelvic adhesions. Some
      animals develop adhesions rapidly, within 2 weeks after a single tubal
      inoculation with Chlamydia trachomatis, while in others, adhesions are not
      observed until 2 weeks after a second tubal inoculation. To test whether this
      variability correlates with major histocompatibility complex (MHC) class I
      haplotype, we used macaque alloantisera and mouse anti-HLA monoclonal antibodies
      to determine the MHC class I haplotypes of 44 C. trachomatis-infected macaques
      (Macaca nemestrina). Macaques developing gross tubal adhesions after the first
      chlamydial inoculation were classified as susceptible (n = 29), while those not
      developing adhesions until after the second chlamydial inoculation were
      classified as relatively resistant (n = 15), to adhesion formation. Three
      antibody specificities correlated with susceptibility (odds ratio [OR] 5.2, P <
      0.01; OR 6.1 and 4.3, P < 0.05), and two correlated with relative resistance to
      adhesions (OR 0.1, P < 0.05; OR 0.2, P < 0.01). Because several of these
      antibodies are cross-reactive, as many as five different MHC class I alleles
      (three increasing and two decreasing ORs) or as few as two different MHC class I
      alleles (one increasing and one decreasing OR) could be correlated with risk of
      adhesion formation. We conclude that in macaques, susceptibility or relative
      resistance to rapid formation of tubal adhesions is correlated with expression of
      MHC class I alleles, consistent with reports of MHC class I restriction of
      chlamydial immunopathology in humans.

PMID- 9169760
TI  - Synergistic effect of mutations in invA and lpfC on the ability of Salmonella
      typhimurium to cause murine typhoid.
AB  - Penetration of the intestinal mucosa at areas of Peyer's patches is an important
      first step for Salmonella typhimurium to produce lethal systemic disease in mice.
      However, mutations in genes that are important for intestinal invasion result in
      only moderately decreased virulence of S. typhimurium for mice. Here we report
      that combining mutations in invA and lpfC, two genes necessary for entry into
      Peyer's patches, results in a much stronger attenuation of S. typhimurium than
      inactivation of either of these genes alone. An S. typhimurium invA lpfC mutant
      was 150-fold attenuated by the oral route of infection but was fully virulent
      when the intestine was bypassed by intraperitoneal challenge of mice. During
      mixed-infection experiments, the S. typhimurium invA lpfC mutant showed a strong
      defect in colonizing Peyer's patches and mesenteric lymph nodes. These data
      suggest that mutations in invA and lpfC deactivate distinct pathways for
      intestinal penetration and colonization of Peyer's patches. While the inv
      mediated pathway is widely distributed, the lpf operon is absent from many
      phylogenetic groups within the genus Salmonella. To investigate how acquisition
      of the lpf-mediated pathway for mucosal penetration contributed to evolution of
      virulence, we studied the relationship between the presence of the lpf operon and
      the pathogenicity for mice of 18 isolates representing 14 Salmonella serotypes.
      Only strains possessing the lpf operon were able to cause lethal infection in
      mice. These data show that both the invA- and lpfC-mediated pathways of
      intestinal perforation are conserved in mouse virulent Salmonella serotypes.

PMID- 9169761
TI  - Two antigens on zygotes and ookinetes of Plasmodium yoelii and Plasmodium berghei
      that are distinct targets of transmission-blocking immunity.
AB  - We have developed transmission-blocking monoclonal antibodies (MAbs) against
      Plasmodium yoelii 21-kDa (Pys21) and 28-kDa (Pys25) ookinete surface proteins.
      These MAbs block infectivity of P. yoelii to Anopheles stephensi. One MAb, 14,
      cross-reacted by Western blotting with a 28-kDa surface protein (Pbs25) of P.
      berghei ookinetes and blocked oocyst development, as assayed by direct mosquito
      feeds on passively immunized P. berghei-infected mice. In total, we have
      identified two ookinete surface proteins in P. yoelii, one of which is also
      present in P. berghei. The transmission-blocking activity of the anti-Pys25 MAb 4
      was complete and more potent than that of the anti-Pys21 MAb 2. Moreover, Fab
      fragments of MAb 4 had transmission-blocking activity in mice. In comparison, Fab
      fragments of MAb 2 did not have detectable transmission-blocking effect, although
      F(ab')2 did. Furthermore, MAb 2 and MAb 4 appeared to block the in vitro
      formation and development of zygotes as well.

PMID- 9169762
TI  - Environmental regulation of fimbrial gene expression in Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis fimbriae are an important virulence factor involved in
      attachment and invasion. Fimbrillin, encoded by the fimA gene, is the major
      subunit protein of the fimbriae. To elucidate the influence of environmental
      signals on the expression of the fimA gene, a strain of P. gingivalis (designated
      PLE) containing a chromosomal transcriptional fusion between a promoterless lacZ
      gene and the fimA promoter region was constructed. Promoter activity was assessed
      by measurement of beta-galactosidase activity of PLE. An 11-fold increase in
      activity of fimA promoter was found as growth temperature declined from 39 to 34
      degrees C. Promoter activity decreased by approximately 50% in response to hemin
      limitation and upon culture on solid medium. In addition, the presence of serum
      or saliva in the growth medium decreased fimA promoter activity by similar
      amounts. A correlation between fimA promoter activity and phenotypic properties
      dependent upon fimbriae was established. P. gingivalis grown at 34 degrees C,
      compared to 39 degrees C, showed an increased ability to adhere to Streptococcus
      gordonii and to invade primary cultures of gingival epithelial cells. These
      studies indicate that expression of the P. gingivalis fimA gene is regulated at
      the transcriptional level in response to several environmental conditions and
      that altered fimA expression can also modulate the adherence and invasion
      abilities of P. gingivalis.

PMID- 9169763
TI  - Saturable CD14-dependent binding of fluorescein-labeled lipopolysaccharide to
      human monocytes.
AB  - We used rough lipopolysaccharide (ReLPS) to construct a fluorescein-labeled LPS
      (FITC-LPS) with a very high labeling efficiency that bound to isolated human
      monocytes in a CD14-dependent fashion and that in this respect behaved
      indistinctively from native LPS. The CD14-dependent binding could be inhibited
      either by a 1,000-fold excess of unlabeled LPS or by polymyxin B,
      bactericidal/permeability-increasing protein, cationic protein 18, or soluble
      CD14. Although this FITC-LPS preparation no longer possessed the ability to prime
      neutrophils for the production of reactive oxygen species or to stimulate human
      monocytes to produce tumor necrosis factor, activation of the Limulus amoebocyte
      lysate cascade was comparable to activation by native LPS. Binding to monocytes
      was enhanced by human pooled serum (HPS) or LPS-binding protein (LBP) for LPS
      concentrations up to 100 ng/ml and was completely CD14 dependent. For LPS
      concentrations exceeding 100 ng/ml, binding was still partially CD14 dependent,
      but not HPS or LBP dependent. CD14-dependent association of LPS with monocytes
      was shown to be totally saturable. In conclusion, we found an HPS- or LBP
      dependent binding of FITC-LPS to monocytes that was CD14 dependent at up to 100
      ng of LPS per ml, and saturation of binding was shown.

PMID- 9169764
TI  - Depletion of alveolar macrophages exacerbates respiratory mycoplasmosis in
      mycoplasma-resistant C57BL mice but not mycoplasma-susceptible C3H mice.
AB  - Indirect evidence suggests that innate immune mechanisms involving alveolar
      macrophages (AMs) are of major importance in antimycoplasmal defense. We compared
      the effects of AM depletion on intrapulmonary killing of Mycoplasma pulmonis
      during the early phase of infection in mycoplasma-resistant C57BL/6NCr (C57BL)
      and mycoplasma-susceptible C3H/HeNCr (C3H) mice. More than 80% of AMs were
      depleted in both strains of mice by intratracheal insufflation of liposome
      encapsulated dichloromethylene bisphosphonate (L-Cl2MBP), compared to no
      significant AM depletion in either strain following insufflation of liposome
      encapsulated phosphate-buffered saline (L-PBS), PBS alone, or no treatment. AM
      depleted (L-Cl2MBP) and control (L-PBS) mice were infected intranasally with
      10(5) CFU of M. pulmonis UAB CT, and their lungs were quantitatively cultured to
      assess intrapulmonary killing at 0, 8, 12, and 48 h postinfection. AM depletion
      exacerbated the infection in C57BL mice by reducing killing of the organism to a
      level comparable to that in C3H mice without AM depletion. In contrast, AM
      depletion did not alter killing in C3H mice. These results directly identify the
      AM as the main effector cell in early pulmonary antimycoplasmal defense and
      suggest that differences in mycoplasmal killing by AMs may explain the resistance
      of C57BL mice and the susceptibility of C3H mice to mycoplasmal infection.

PMID- 9169765
TI  - Distinct mechanisms of immunosuppression as a consequence of major surgery.
AB  - Altered host defense mechanisms after major surgery or trauma are considered
      important for the development of infectious complications and sepsis. In the
      present study, we demonstrate that major surgery results in a severe defect of T
      lymphocyte proliferation and cytokine secretion in response to coligation of the
      antigen receptor complex and CD28. During the early postoperative course, reduced
      cytokine secretion was observed for interleukin-2 (IL-2), gamma interferon, and
      tumor necrosis factor alpha, which are associated with the Th1 phenotype of
      helper T lymphocytes, and for IL-4, the index cytokine of Th2 cells. During the
      late postoperative course, T-cell cytokine secretion increased to normal levels.
      Production of the anti-inflammatory cytokine IL-10 was altered, with different
      kinetics being selectively elevated during the late postoperative course. In
      contrast, the capacity of peripheral blood monocytes to present bacterial
      superantigens and to stimulate T-cell proliferation was normal or enhanced after
      surgery despite a significant loss of cell surface HLA-DR molecules. Thus, the
      level of major histocompatibility complex class II protein expression does not
      appear to predict the antigen-presenting capacity of monocytes obtained from
      surgical patients with uneventful postoperative recovery. Secretion of IL-1beta
      and IL-10 by endotoxin-stimulated peripheral blood monocytes was increased at
      different time points after surgery. Major surgery therefore results in a
      distinct pattern of immune defects with a predominant defect in the T-cell
      response to T-cell receptor- and CD28 coreceptor-mediated signals rather than an
      impaired monocyte antigen-presenting capacity. Suppression of T-cell effector
      functions during the early phase of the postoperative course may define a state
      of impaired defense against pathogens and increased susceptibility to infection
      and septic complications.

PMID- 9169766
TI  - Effects of antibodies against cell surface protein antigen PAc
      glucosyltransferase fusion proteins on glucan synthesis and cell adhesion of
      Streptococcus mutans.
AB  - Cell surface protein antigen (PAc) and glucosyltransferases (GTFs) produced by
      Streptococcus mutans are considered to be major colonization factors of the
      organism, and the inhibition of these two factors is predicted to provide
      protection against dental caries. In this study, we have constructed fusion
      protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc
      with the glucan binding (GB) domain of GTF-I, an enzyme catalyzing the synthesis
      of water-insoluble glucan from sucrose, and fusion protein PAcA-SB, a fusion of
      PAcA with the sucrose binding (SB) domain of GTF-I. The recombinant fusion
      proteins were purified from cell extracts of Escherichia coli harboring the
      fusion genes, and rabbit antibodies against these fusion proteins were prepared.
      Water-insoluble glucan synthesis by cell-associated and cell-free GTF
      preparations from S. mutans as well as total glucan synthesis by GTF-I was
      markedly inhibited by anti-PAcA-GB immunoglobulin G (IgG) antibodies but not by
      anti-PAcA-SB IgG antibodies. Significant inhibition of the sucrose-independent
      and sucrose-dependent adhesion of S. mutans to saliva-coated hydroxyapatite beads
      was observed when anti-PAcA-GB antibodies were added to the reaction mixture.
      Anti-PAcA-SB antibodies inhibited the adhesion of S. mutans to the beads in the
      absence of sucrose but not in the presence of sucrose. Immunization with the
      fusion protein PAcA-GB may be useful for controlling the colonization of teeth by
      S. mutans.

PMID- 9169767
TI  - The decrease in nonsplenic interleukin-6 (IL-6) production after splenectomy
      indicates the existence of a positive feedback loop of IL-6 production during
      endotoxemia in dogs.
AB  - The spleen is involved in endotoxin-induced interleukin-6 (IL-6) production. To
      quantitate the relative contribution of the spleen to endotoxin-induced IL-6
      production, we studied the effect of endotoxin (1.0 microg/kg of body weight) in
      control dogs (n = 7) and splenectomized dogs (n = 7). Blood for analysis of tumor
      necrosis factor (TNF) and IL-6 was sampled from the femoral artery and the
      portal, hepatic, and splenic (only in controls) veins. Arterial plasma endotoxin
      and cortisol levels were also measured. Whole-body IL-6 production was calculated
      by a deconvolution technique. Splenic IL-6 production in control dogs was
      measured from splenic blood flow and arteriovenous concentration differences.
      Endotoxin levels were higher in splenectomized dogs (P < 0.05) because of a
      decreased distribution volume (P < 0.05) and decreased clearance of endotoxin (P
      < 0.05). Endotoxin-induced plasma IL-6 levels were decreased by approximately 75%
      in splenectomized dogs (P < 0.01), and whole-body IL-6 production rates were
      severalfold lower (median of 8.7 mg/4 h and range of 3.9 to 11.4 mg/4 h versus a
      median of 32.3 mg/4 h and a range of 22.7 to 70.2 mg/4 h) (P < 0.05). However, in
      control dogs splenic IL-6 production (0.6 +/- 0.2 mg/4 h) was only approximately
      2% of whole-body IL-6 production. Plasma TNF levels increased in both groups (P <
      0.01) but were not different between the groups. Plasma cortisol levels were
      slightly higher in splenectomized dogs than in control dogs (P < 0.05). In
      conclusion, splenectomy decreases the distribution volume and clearance rate of
      endotoxin. Splenectomy results in decreased endotoxin-induced IL-6 production,
      which is caused not by the absence of splenic IL-6 production, but by a decrease
      in nonsplenic IL-6 production. Therefore, the spleen is an important mediator in
      the complete activation of nonsplenic IL-6 production by endotoxin.

PMID- 9169768
TI  - Role of alphabeta and gammadelta T cells in the host response to Salmonella
      infection as demonstrated in T-cell-receptor-deficient mice of defined Ity
      genotypes.
AB  - Salmonella spp. are facultative intracellular bacteria which enter the body
      through the intestinal tract. We studied the roles of T cells expressing either
      the alpha and beta chains or the gamma and delta chains of the T-cell receptor
      (alphabeta T cells or gammadelta T cells, respectively) in the host defense
      against Salmonella using mice genetically deficient in either alphabeta T cells,
      gammadelta T cells, or both T-cell subsets. These mutant strains of mice were
      infected orally or intraperitoneally with Salmonella dublin, and the progression
      of the disease was monitored by determining bacterial numbers in the feces, gut
      wall, Peyer's patches, mesenteric lymph nodes, spleen, and liver. Since
      susceptibility to Salmonella infection in mice is strongly affected by the
      alleles at the Ity locus, T-cell-mutant mice with either the Ity-sensitive or Ity
      resistant phenotype were tested for resistance to S. dublin infection. We found
      that even though large numbers of intraepithelial and mucosal alphabeta and
      gammadelta T cells populate the normal intestine, they have no role in
      controlling the invasion of S. dublin into the intestine or the subsequent
      bacterial replication in the Peyer's patches or gut wall. Furthermore, systemic
      infections were equally severe for the first 6 days in normal, alphabeta T-cell
      deficient, and gammadelta T-cell-deficient mice, and alphabeta but not gammadelta
      T cells were required for clearance of S. dublin, regardless of the Ity
      phenotype. However, mice that lacked both T-cell subsets had higher bacterial
      counts in their livers 15 to 18 days after infection than did alphabeta T-cell
      deficient mice, suggesting that gammadelta T cells can contribute to acquired
      immunity to S. dublin.

PMID- 9169770
TI  - High-level heterologous expression and secretion in rapidly growing nonpathogenic
      mycobacteria of four major Mycobacterium tuberculosis extracellular proteins
      considered to be leading vaccine candidates and drug targets.
AB  - Mycobacterium tuberculosis, the primary etiologic agent of tuberculosis, is the
      world's leading cause of death from a single infectious agent, and new vaccines
      and drugs to combat it are urgently needed. The major extracellular proteins of
      M. tuberculosis, which are released into its phagosome in macrophages, its host
      cells in humans, are leading candidates for a vaccine and prime targets for new
      drugs. However, the development of these biologicals has been hampered by the
      unavailability of large quantities of recombinant extracellular proteins
      identical to their native counterparts. In this report, we describe the
      heterologous expression and secretion of four major M. tuberculosis extracellular
      proteins (the 30-, 32, 16-, and 23.5-kDa proteins--the first, second, third, and
      eighth most abundant, respectively) in rapidly growing, nonpathogenic
      mycobacterial species. Multiple attempts to obtain secretion of the proteins by
      using Escherichia coli- and Bacillus subtilis-based expression systems were
      unsuccessful, suggesting that high-level expression and secretion of these
      Mycobacterium-specific proteins require a mycobacterial host. All four
      recombinant proteins were stably expressed from the cloned genes' own promoters
      at yields that were 5- to 10-fold higher than those observed for the native
      proteins. The four proteins were purified to apparent homogeneity from culture
      filtrates by ammonium sulfate precipitation and ion-exchange and molecular sieve
      chromatography. The recombinant proteins were indistinguishable from their native
      counterparts by multiple criteria. First, N-terminal amino acid sequence
      determination demonstrated that processing of the leader peptides was highly
      accurate. Second, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis revealed identical migration patterns. Third, mass spectrometry analysis
      confirmed that differences in mass were < or = 5 Da. A homolog of the M.
      tuberculosis 30-kDa protein was identified in M. smegmatis by means of DNA
      analyses and immunoscreening. This is the first time that secretion of
      recombinant M. tuberculosis extracellular proteins in their native form has been
      achieved. This study opens the door to mass production of correctly processed and
      secreted extracellular proteins of M. tuberculosis in a heterologous host and
      allows ready evaluation of their biologic and immunologic function.

PMID- 9169769
TI  - Clostridium perfringens urease genes are plasmid borne.
AB  - Although many bacteria are ureolytic, and in some cases urease acts as a
      virulence factor, the urease phenotype has not been analyzed in the anaerobic
      pathogen Clostridium perfringens. In this study, approximately 2% of C.
      perfringens strains, representing the principal biotypes, were found to harbor
      the urease structural genes, ureABC, and these were localized on large plasmids
      that often encode, in addition, the lethal epsilon or iota toxins or the
      enterotoxin. This represents the first report of a plasmid-encoded urease in a
      gram-positive bacterium. The C. perfringens enzyme was highly similar to the
      ureases of other bacteria and cross-reacted with antibodies raised against the
      urease purified from Helicobacter pylori. Urease production was inhibited by urea
      and induced under growth conditions where the availability of nitrogen sources
      was limiting. To date, this form of regulation has been observed only for
      chromosomal ureABC genes.

PMID- 9169771
TI  - Assessment of the humoral immune response against Plasmodium falciparum rhoptry
      associated proteins 1 and 2.
AB  - Naturally occurring antibody responses to Plasmodium falciparum rhoptry
      associated proteins 1 and 2 (RAP-1 and RAP-2) were measured with recombinant and
      parasite-derived forms of the antigens. For comparative purposes, responses to
      multiple forms of three other malarial antigens were also examined. The sera of
      100 Papua New Guineans were screened for antibodies. Eighty-six and 82% of
      individuals over 30 years of age had antibodies that recognized parasite-derived
      RAP-1 and RAP-2, respectively. Importantly, we found that recombinant and native
      antigens share linear epitopes seen by the human immune system; thus, the
      recombinant proteins may be adequate human immunogens. However, antibodies
      affinity purified on recombinant RAP-1 reacted with other antigens in addition to
      parasite-derived RAP-1. Thus, the antigenicity of RAP-1 may have been
      overestimated previously. The recognition of RAP-1 and RAP-2 correlated with age
      and with the recognition of recombinant forms of the ring-infected erythrocyte
      surface antigen, merozoite surface protein 1, and merozoite surface antigen 2
      (MSA2) antigens. Antibodies to these antigens appear to be generated in response
      to the total exposure to malaria of the host. Antibodies to conserved regions of
      MSA2 had stronger correlations with both age and the recognition of other
      antigens than did the full-length recombinant MSA2 molecule. In contrast to
      results with the other antigens, there was no significant difference in the ages
      of individuals with a certain antibody titer to the full-length recombinant or
      parasite-derived MSA2 molecule, but antibodies to these two antigens did
      correlate with parasitemia. For all antigens tested, antibody levels after two
      infections can approach the peak levels of antibodies obtained in immune
      individuals.

PMID- 9169772
TI  - Impaired resistance to the development of toxoplasmic encephalitis in interleukin
      6-deficient mice.
AB  - The role of interleukin-6 (IL-6) in the pathogenesis of toxoplasmic encephalitis
      (TE) was examined by using IL-6-targeted mutant (IL-6(-/-)) mice. At 4 and 8
      weeks after infection with the ME49 strain of Toxoplasma gondii, significantly
      greater numbers of T. gondii cysts and areas of inflammation associated with
      tachyzoites were observed in brains of IL-6(-/-) mice than in those of control
      mice. Large areas of necrosis were observed only in brains of IL-6(-/-) mice.
      Tachyzoites were frequently detected in the areas of necrosis, suggesting that
      necrosis was caused by proliferation of the parasite. These results indicate that
      IL-6 is protective against development of TE by preventing formation of T. gondii
      cysts and proliferation of tachyzoites in brains of infected mice. Whereas in
      brains of control mice, large numbers of inflammatory cells were always observed
      in areas where tachyzoites were detected, in brains of IL-6(-/-) mice, only small
      numbers of inflammatory cells were observed in many areas with tachyzoites.
      Lymphocyte preparations isolated from brains of infected control mice had
      significantly higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells
      but lower ratios of CD8+ alpha/beta T cells compared to those of infected IL-6(-/
      ) mice. There were no differences in the ratios of these T-cell subsets in
      spleens between these mice. The amounts of mRNA for gamma interferon (IFN-gamma)
      detected by reverse transcriptase PCR were significantly smaller in brains of IL
      6(-/-) mice than in those of control mice, whereas amounts of IL-10 mRNA were
      greater in the former than in the latter. IL-6 mRNA was detected only in infected
      control mice. The protective activity of IL-6 against development of TE appears
      to be through its ability to stimulate IFN-gamma production and induce
      infiltration and accumulation of different T-cell subsets in brains of infected
      mice.

PMID- 9169773
TI  - Characterization of the canine type C enterotoxin produced by Staphylococcus
      intermedius pyoderma isolates.
AB  - The type C staphylococcal enterotoxins (SECs) are a group of highly conserved
      proteins with substantial antigenic cross-reactivity. Although Staphylococcus
      intermedius and coagulase-positive species of staphylococci are reported to
      produce SEC and other SEs, toxins produced by species other than Staphylococcus
      aureus have not been previously characterized. In this study we report the
      molecular, biological, and immunological properties of the canine SEC (SECcanine)
      expressed by pathogenic isolates of S. intermedius. The mature form of SECcanine
      has 239 amino acid residues and a pI of 7.0. Typical of the SEs, purified
      SECcanine induces an emetic response in monkeys and the proliferation of T cells
      in a Vbeta-dependent manner. Although SECcanine has >95% sequence identity to
      previously described SEC variants, its sequence is most related to SEC2 and SEC3.
      In contrast to the sequence similarity, the Vbeta profile induced by SECcanine is
      typical of that induced by SEC1. This result is likely explained by the
      conservation of a cysteine residue at position 26 in SECcanine; residues at this
      position have been previously shown to determine subtype-dependent differences in
      T-cell receptor interactions of other SEs. Overall, these results show that
      superantigen toxins produced by the multiple members of the genus Staphylococcus
      are highly conserved in respect to biological and structural properties. Further,
      the frequent association of SECcanine with pyoderma in dogs supports the notion
      that the toxins are important for staphylococcal survival and pathogenesis.

PMID- 9169774
TI  - Differential recognition of members of the carcinoembryonic antigen family by Opa
      variants of Neisseria gonorrhoeae.
AB  - Opacity (Opa) protein variation in Neisseria gonorrhoeae is implicated in the
      pathogenesis of gonorrhea, possibly by mediating adherence and entry of the
      bacteria into human tissues. One particular Opa protein mediates adherence to
      epithelial cells through cell surface proteoglycans. Recently, two other
      eukaryotic cell receptors for Opa proteins have been reported. These receptors
      are members of a subgroup of the carcinoembryonic (CEA) gene family that express
      CD66 antigens. CEA family members vary in their distribution in human tissues. In
      order to understand whether interactions between Opa and CEA-like molecules play
      any role in pathogenesis, we must investigate which CEA family members are able
      to serve as Opa receptors and which Opa proteins recognize CEA-like molecules. We
      therefore studied HeLa cells that were stably transfected with five different
      members of the CEA family, i.e., CEA, CEA gene family member 1a (CGM1a), CGM6,
      nonspecific cross-reacting antigen (NCA), and biliary glycoprotein a (BGPa). We
      infected these transfectants with all possible 11 Opa variants of gonococcal
      strain MS11 and determined the numbers of bacteria that were bound and
      internalized. To account for proteoglycan-mediated adherence, infection assays
      were also performed in the presence of heparin. Our results show that of the 11
      Opa variants of MS11, the same 4 recognized CGM1a and NCA. CGM6, however, was not
      recognized by any Opa variant of MS11. CEA was recognized by at least 9 of 11 Opa
      variants, and the BGP transfectants specifically bound and internalized 10 of 11
      Opa variants and also bound Opa-negative gonococci. Immunofluorescence
      experiments showed that clustering of CEA-like molecules occurred upon infection
      of HeLa transfectants with those Opa variants that interacted specifically with
      the CEA family member. Together these data show that CEA family members are
      differentially recognized by gonococcal Opa variants, suggesting that this
      phenomenon may contribute to cell tropism displayed by gonococci.

PMID- 9169776
TI  - Adjuvanticity and protective immunity elicited by Leishmania donovani antigens
      encapsulated in positively charged liposomes.
AB  - In the search for a leishmaniasis vaccine, extensive studies of cutaneous
      leishmaniasis have been carried out. Investigations in this regard with the
      visceral form are limited. As an initial step in the identification of the
      protective molecules, leishmanial antigens extracted from the membranes of
      Leishmania donovani promastigotes, alone or in association with liposomes, were
      evaluated for their immunogenicity and ability to elicit a protective immune
      response against challenge infection. Intraperitoneal immunization of hamsters
      and BALB/c mice with the leishmanial antigens conferred protection against
      infection with the virulent promastigotes. Encapsulation in positively charged
      liposomes significantly enhanced the protective efficacy of these antigens. The
      splenic parasite burden of hamsters was reduced by 97% after 6 months of
      infection. BALB/c mice exhibited 87 and 81.3% protection in the liver and spleen,
      respectively, after 4 months of infection. These protected animals elicited
      profound delayed-type hypersensitivity and increased levels of Leishmania
      specific immunoglobulin G (IgG) antibodies. Protection in mice also coincided
      with elevated levels of IgM and IgA antibodies, which decreased with disease
      progression in the control-infected animals. Although both IgG1 and IgG2a
      antibodies were present in the sera of infected mice, IgG1 appeared to be the
      predominant isotype, suggesting a preferential induction of the Th2 type of
      immune response over that of Th1. Effective stimulation of all the IgG isotypes,
      particularly IgG2a, after immunization with liposome encapsulated antigens seems
      to be responsible for the significant levels of resistance against the disease.
      Taken together, these data indicate a potential for the liposomal antigens as a
      vaccine which could trigger both humoral and cell-mediated immune responses.

PMID- 9169775
TI  - The role of tyrosine phosphorylation in lipopolysaccharide- and zymosan-induced
      procoagulant activity and tissue factor expression in macrophages.
AB  - The expression of surface procoagulants by exudative macrophages represents an
      important mechanism underlying local fibrin deposition at sites of extravascular
      inflammation. The present studies investigated the contribution of tyrosine
      phosphorylation to the generation of macrophage procoagulant activity (PCA) and
      tissue factor expression in response to proinflammatory stimuli. Both
      lipopolysaccharide (LPS) and zymosan rapidly stimulated tyrosine phosphorylation
      in elicited murine peritoneal macrophages. This effect was prevented by the
      tyrosine kinase inhibitors genistein and herbimycin and augmented by the addition
      of the phosphotyrosine phosphatase inhibitor vanadate. The vanadate-mediated rise
      in phosphotyrosine accumulation was abrogated by the use of diphenylene iodonium,
      an inhibitor of the respiratory burst oxidase, suggesting a role for peroxides of
      vanadate as contributors to the tyrosine phosphorylation. This notion was
      supported by the finding that vanadyl hydroperoxide markedly increased the
      accumulation of phosphotyrosine residues. To define the role of tyrosine
      phosphorylation in the induction of macrophage PCA by LPS, the effects of
      tyrosine kinase inhibition by genistein and herbimycin were investigated. Both
      agents inhibited the expression of macrophage PCA. Further, Northern blot
      analysis with the cDNA probe for murine tissue factor indicated that the
      inhibition occurred at the mRNA level or earlier. Since vanadate augmented
      phosphotyrosine accumulation, it was hypothesized that it might enhance
      generation of macrophage products. However, vanadate reduced induction of PCA in
      response to LPS. By contrast, vanadate augmented basal prostaglandin E2 (PGE2)
      release and stimulated PGE2 release by macrophages. Indomethacin prevented the
      increase in PGE2 but only partially restored normal levels of PCA. The effect of
      vanadate on tissue factor expression appeared to be posttranscriptional. These
      studies thus demonstrate, by functional Western blotting and Northern blotting
      techniques, that tyrosine phosphorylation plays a role in the regulation of
      macrophage PCA and tissue factor expression in response to proinflammatory
      stimuli.

PMID- 9169777
TI  - Lipopolysaccharide-induced interleukin 8 production by human whole blood is
      enhanced by epinephrine and inhibited by hydrocortisone.
AB  - To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide
      (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated
      with LPS in the presence or absence of these stress hormones. Epinephrine caused
      a dose-dependent increase in LPS-induced IL-8 production, which was mediated
      exclusively via beta-adrenergic receptors, as reflected by the facts that beta
      (but not alpha) receptor blockade reversed the epinephrine effect and beta (but
      not alpha) receptor stimulation reproduced the epinephrine effect. Further,
      elevating cellular cyclic AMP (cAMP) concentrations, a known effect of beta
      adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced
      IL-8 production. Epinephrine-induced upregulation of IL-10 production masked an
      even more pronounced stimulating effect of this hormone on IL-8 synthesis, as
      indicated by the finding that the extent of IL-8 upregulation was greater in the
      presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose
      dependently inhibited LPS-induced IL-8 production and reversed epinephrine
      induced enhancement of IL-8 production. Epinephrine and hydrocortisone have
      opposite effects on IL-8 production, which may be relevant for the understanding
      of endogenous and therapeutic stress hormone influences on IL-8 mediated
      inflammation.

PMID- 9169778
TI  - Immunomodulatory properties of porins of some members of the family
      Enterobacteriaceae.
AB  - The outer membrane protein (OMP) preparation of Salmonella typhi was observed to
      have several immunomodulatory properties. Treatment of mice with an
      intraperitoneal injection of the OMP preparation enhanced both cellular and
      humoral responses of the mice to an unrelated antigen, a killed vaccine of
      Mycobacterium vaccae; both the delayed-type hypersensitivity (DTH) response and
      the antibody titers were enhanced. The predominant isotype of the antibody
      shifted from immunoglobulin G1 (IgG1) to IgG2a upon treatment with OMP. Treatment
      of mice with the OMP preparation improved the efficiency of in vitro antigen
      presentation by the peritoneal cells and also induced the cells to secrete
      interleukin-1. Treatment with the lipopolysaccharide (LPS) preparation of S.
      typhi had the opposite effect; i.e., the DTH response to M. vaccae was
      suppressed. Treatment with OMP neutralized the suppressive effects of LPS. The
      OMP preparation also had an enhancing effect on the innate immune mechanisms of
      the mice. Intraperitoneal injection of the OMP preparation enhanced the
      microbicidal activity of the peritoneal cells, and production of nitric oxide
      intermediates was stimulated. Injection of the OMP preparation into footpads of
      naive nonimmune mice induced a sustained hypersensitivity response that peaked at
      24 h. Purified porins of the OMP preparation could induce both immunomodulation
      and hypersensitivity. Porins prepared from five different Salmonella strains and
      a strain of normal fecal Escherichia coli also exhibited immunomodulatory and
      hypersensitivity-inducing activities.

PMID- 9169779
TI  - Localization of human intestinal defensin 5 in Paneth cell granules.
AB  - Antibiotic peptides of higher animals include the defensins, first discovered in
      phagocytic cells but recently also found to be produced by epithelial cells. We
      biosynthesized recombinant human intestinal defensin 5 (rHD-5) using the
      baculovirus-insect cell expression system. Since insect cells process defensin
      incompletely and secrete the precursor proHD-5, we substituted a methionine for
      an alanine at a likely processing site to allow selective chemical cleavage with
      cyanogen bromide, and rHD-5 was used to elicit polyclonal antibodies. By the
      immunoperoxidase-staining technique, the antibodies selectively stained Paneth
      cells of the normal adult small intestine. Immunogold electron microscopy further
      localized HD-5 to the Paneth cell secretory granules. Since some defensins exert
      activity cytotoxic to mammalian cells, we assayed the effect of rHD-5 on the
      human intestinal cell lines Caco2 and Int407. proHD-5 did not exert cytotoxic
      activity, and rHD-5 showed only minimal activity against Int407 and was inert
      against Caco2. Since Paneth cells release their granules adjacent to the mitotic
      cells of the intestinal crypts, HD could protect this cell population against
      invasion and parasitization by microbes.

PMID- 9169780
TI  - Broad-spectrum antimicrobial activity of human intestinal defensin 5.
AB  - Defensins are antibiotic peptides expressed in human and animal myeloid and
      epithelial cells. Due to the limited availability of natural peptides, the
      properties of human epithelial defensins have not been studied. We assayed the
      microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the
      presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin
      (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria
      monocytogenes, Escherichia coli, and Candida albicans. In contrast to cryptdins,
      the mouse intestinal defensins, rHD-5 is active against both mouse-virulent wild
      type Salmonella typhimurium and its isogenic, mouse-avirulent phoP mutant. In the
      presence of salt, rHD-5 activity was reduced, and at 100 mM NaCl, activity
      against S. typhimurium was abolished. However, at all salt concentrations tested,
      rHD-5 remained bactericidal to L. monocytogenes. Activity against L.
      monocytogenes was not pH dependent but was diminished at pH 5.5 against wild-type
      S. typhimurium. This acid-induced resistance may have been mediated by the
      virulence gene regulator phoP, since the phoP mutant was equally sensitive at pH
      5.5 and pH 7.4. In the presence of trypsin, rHD-5 was partially cleaved, but even
      then, rHD-5 at 100 microg/ml decreased the number of CFU of wild-type S.
      typhimurium by more than 99%. The persistence of microbicidal activity of rHD-5
      under these conditions supports the notion that naturally occurring human
      intestinal defensin is an effective arm of mucosal host defense.

PMID- 9169782
TI  - Alterations in levels of DnaK and GroEL result in diminished survival and
      adherence of stressed Haemophilus ducreyi.
AB  - Haemophilus ducreyi is a hemin-requiring bacterium causing the genital ulcer
      disease chancroid. Previously we demonstrated that the heat shock protein GroEL
      was immunogenic and possibly highly expressed in a mammalian host. The present
      study was initiated to (i) determine the relative amounts of GroEL expressed by
      H. ducreyi during in vitro exposure to stresses and (ii) evaluate whether a high
      level of GroEL is directly or indirectly required for survival and adherence of
      stressed H. ducreyi. Using scanning densitometry of sodium dodecyl sulfate
      polyacrylamide gel electrophoresis protein profiles, we found that H. ducreyi
      expressed high basal levels of GroEL, averaging fivefold greater than in
      Escherichia coli. These high GroEL levels increased up to twofold upon exposure
      of the organism to heat shock or high levels of hydrogen peroxide and during
      adherence to two human genital cell lines. Furthermore, when the gene for DnaK
      was present on a multicopy plasmid in H. ducreyi, a 1.8-fold increase in DnaK and
      a 2.3-fold reduction in GroEL were seen. These results suggest that DnaK serves
      as a negative modulator of H. ducreyi GroEL. Subsequently we found that H.
      ducreyi with lower GroEL had diminished ability to survive when challenged by
      heat and oxidative stresses. In addition, the long, parallel chains
      characteristic of virulent strains of H. ducreyi were absent when GroEL was
      lowered, so that fewer bacterial cells adhered to the human cells. These results
      suggest that the unusually high basal levels of GroEL are involved, either
      directly or indirectly, in the survival, chaining, and adherence of H. ducreyi in
      the presence of the combined stresses of the host environment.

PMID- 9169781
TI  - Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding
      protein in live attenuated Salmonella vaccine strains.
AB  - Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against
      several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus
      (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to
      fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion
      protein was equally expressed in several attenuated vaccine strains derived from
      bacteria with different genetic backgrounds and different attenuating mutations.
      Single-dose immunization experiments with the aroA Salmonella typhimurium strain
      SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both
      the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1
      and the antigen-specific cytokine production in spleen cells were stronger in
      mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed
      sections of the worm's larval stage. Analysis of the isotype distribution of the
      specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1
      (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation
      of spleen cells from mice immunized with the different constructs with either
      Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related
      cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a
      Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the
      response to the Salmonella carrier and to the recombinant antigens. Salmonellae
      expressing the TetC-rEgDfl fusion are currently under evaluation as potential
      vaccines against E. granulosus.

PMID- 9169783
TI  - Ultrastructural analysis of primary human urethral epithelial cell cultures
      infected with Neisseria gonorrhoeae.
AB  - In men with gonococcal urethritis, the urethral epithelial cell is a site of
      infection. To study the pathogenesis of gonorrhea in this cell type, we have
      developed a method to culture primary human urethral epithelial cells obtained at
      the time of urologic surgery. Fluorescent analysis demonstrated that 100% of the
      cells stained for keratin. Microscopic analyses indicated that these epithelial
      cells arrayed in a pattern similar to that seen in urethral epithelium. Using
      immunoelectron and confocal microscopy, we compared the infection process seen in
      primary cells with events occurring during natural infection of the same cell
      type in men with gonococcal urethritis. Immunoelectron microscopy studies of
      cells infected with Neisseria gonorrhoeae 1291 Opa+ P+ showed adherence of
      organisms to the epithelial cell membrane, pedestal formation with evidence of
      intimate association between the gonococcal and the epithelial cell membranes,
      and intracellular gonococci present in vacuoles. Confocal studies of primary
      urethral epithelial cells showed actin polymerization upon infection. Polyclonal
      antibodies to the asialoglycoprotein receptor (ASGP-R) demonstrated the presence
      of this receptor on infected cells in the primary urethral cell culture. In situ
      hybridization using a fluorescent-labeled probe specific to the ASGP-R mRNA
      demonstrated this message in uninfected and infected cells. These features were
      identical to those seen in urethral epithelial cells in exudates from males with
      gonorrhea. Infection of primary urethral cells in culture mimics events seen in
      natural infection and will allow detailed molecular analysis of gonococcal
      pathogenesis in a human epithelial cell which is commonly infected.

PMID- 9169784
TI  - Localization of alpha/beta and gamma/delta T lymphocytes in Cryptosporidium
      parvum-infected tissues in naive and immune calves.
AB  - The nature of the host's T-lymphocyte population within the intestinal villi
      following Cryptosporidium parvum infection was characterized with a bovine model
      of cryptosporidiosis. In naive animals, infection with C. parvum resulted in
      substantial increases in the numbers of alpha/beta T cells, both CD4+ (150%) and
      CD8+ (60%), and of gamma/delta T cells (70%) present within the intestinal villi
      of the infected ileum. In immune animals, the host T-lymphocyte response to a
      challenge infection with C. parvum was restricted to alpha/beta T cells. The
      number of CD4+ T cells within the Peyer's patch of the ileum increased
      dramatically; however, there was little change in the number or localization of
      CD4+ T cells within the intestinal villi. In contrast, the number of CD8+ T cells
      within the intestinal villi increased following a challenge infection. In
      addition, the CD8+ T cells were found to be intimately associated with the
      epithelial cells of the intestinal villi. The precise correlation between the
      accumulation of CD8+ T cells and the normal site of parasite development suggests
      an important role for CD8+ T cells in the immune animal.

PMID- 9169785
TI  - Chlamydia trachomatis growth stimulates interleukin 8 production by human
      monocytic U-937 cells.
AB  - Growth of Chlamydia trachomatis serotypes L2 and L3 in a human monocytic cell
      line, U-937, increased the rate of interleukin 8 (IL-8) release 100-fold. Heat
      killed chlamydiae induced a 10-fold-lower level of production of IL-8. IL-8 may
      play an important role in the inflammatory reaction to chlamydial infection.

PMID- 9169787
TI  - Pathologic changes during acute Q fever: influence of the route of infection and
      inoculum size in infected guinea pigs.
AB  - As assessed by both standard histological staining and immunochemistry,
      intraperitoneal inoculation of C. burnetii in guinea pigs led to pathologic
      changes mainly in the liver, whereas intranasal inoculation led to pathologic
      changes mainly in the lungs. Myocarditis and positive blood cultures were
      observed only in those animals which received the highest inoculum. We therefore
      conclude that both the route of infection and the size of the inoculum influence
      clinical expression in acute Q fever.

PMID- 9169786
TI  - Distribution of endosomal, lysosomal, and major histocompatability complex
      markers in a monocytic cell line infected with Chlamydia psittaci.
AB  - The intracellular fate of Chlamydia psittaci during infection of a monocytic cell
      line, THP1, was characterized. Cytochalasin D inhibited phagocytosis of latex
      beads but had no effect on infection by C. psittaci, and vacuoles expressed the
      transferrin receptor, suggesting accessibility to the endocytic pathway. Early
      Chlamydia-containing vacuoles expressed major histocompatibility complex (MHC)
      class I molecules, and most vacuoles fused with host cell lysosomes, since they
      expressed LAMP-1 and had acidic pHs. In cells prestimulated with gamma
      interferon, vacuoles also expressed MHC class II molecules, suggesting that the
      monocytes might effectively process Chlamydia-derived antigens for presentation
      by MHC class I and class II molecules.

PMID- 9169788
TI  - Efficient immunity against Leishmania major in the absence of interleukin-6.
AB  - Mice genetically deficient in the pleiotropic cytokine interleukin-6 (IL-6)
      exhibit immunodeficiency against viral, bacterial, and fungal pathogens. When
      challenged with the protozoan parasite Leishmania major, IL-6-deficient mice
      controlled infection and mounted strong Th1 responses as efficiently as IL-6
      sufficient littermates. Thus, the successful activation of parasitized
      macrophages and class II-restricted T cells does not require a full inflammatory
      repertoire.

PMID- 9169789
TI  - Avirulence of LT2 strains of Salmonella typhimurium results from a defective rpoS
      gene.
AB  - In order to identify the genetic basis for the attenuation of Salmonella
      typhimurium LT2 strains, experiments were performed to identify a gene(s) which
      restores virulence to an avirulent LT2 strain. These and further experiments
      confirmed that an rpoS mutation is the sole determinant of the attenuation of S.
      typhimurium LT2.

PMID- 9169790
TI  - Interleukin-6 production by human monocytes stimulated with Cryptococcus
      neoformans components.
AB  - In order to ascertain if Cryptococcus neoformans components can induce
      interleukin-6 (IL-6) production, we stimulated human whole blood with purified
      capsular products. Their potencies in stimulating IL-6 release were mannoproteins
      > galactoxylomannan = glucuronoxylomannan > alpha(1-3)glucan. IL-6 production was
      tumor necrosis factor alpha independent and required the presence of monocytes
      and plasma. Since IL-6 can stimulate replication of the human immunodeficiency
      virus in monocytic cells, these findings may be clinically relevant.

PMID- 9169791
TI  - Infection of BALB/c mice with the filarial nematode Litomosoides sigmodontis:
      role of CD4+ T cells in controlling larval development.
AB  - Litomosoides sigmodontis is the only filaria which develops from infective larvae
      into adults in immunocompetent laboratory mice. Depletion of CD4+ T cells from
      infected BALB/c mice resulted in worm and microfilarial burdens significantly
      higher than those of infected controls. Th2 cytokines, eosinophilia, and
      immunoglobulin E, which were strongly induced in infected controls, were
      diminished in CD4-depleted mice.

PMID- 9169792
TI  - Characterization of Shigella type 1 fimbriae: expression, FimA sequence, and
      phase variation.
AB  - This study documents the presence of type 1 fimbriae on Shigella and confirms
      these mannose-sensitive adherence structures to be bona fide components of the
      Shigella surface. While laboratory-passaged Shigella strains and lyophilized
      clinical isolates failed to express type 1 fimbriae, 6 of 20 recent clinical
      isolates, including 4 Shigella flexneri strains, 1 Shigella boydii strain, and 1
      Shigella dysenteriae strain, produced type 1 fimbriae as detected by mannose
      sensitive hemagglutination (MSHA) and electron microscopy. Optimal production of
      a predominantly Fim+ population required serial passage every 48 to 72 h in
      unshaken brain heart infusion broth at 37 degrees C. Fim+ Shigella cultures were
      capable of reversibly switching to a non-MSHA, afimbriated phase during serial
      aerobic cultivation on tryptic soy agar plates. The amino acid sequence of S.
      flexneri type 1 FimA contained 18 substitutions compared to that of Escherichia
      coli fimbrillin. Indirect immunoelectron microscopy suggested the presence of
      both shared and unique epitopes on E. coli and S. flexneri type 1 fimbriae.
      Random phase variation between fimbriated and afimbriated states in Shigella was
      accompanied by the genomic rearrangement associated with phase variation in E.
      coli.

PMID- 9169793
TI  - Adherence of Mycoplasma gallisepticum involves variable surface membrane
      proteins.
AB  - Adherence of Mycoplasma gallisepticum to erythrocytes was examined by colony
      immunoblotting, detergent phase fractionation, trypsin treatment, comparison of
      protein profiles, and comparison of erythrocyte-bound mycoplasma protein
      fractions of hemadsorption-positive and -negative mutants. The binding of M.
      gallisepticum to chicken or human erythrocytes was found to be mediated via
      surface-exposed membrane proteins undergoing high-frequency phase variation.

PMID- 9169794
TI  - Conversion of M serotype 24 of Streptococcus pyogenes to M serotypes 5 and 18:
      effect on resistance to phagocytosis and adhesion to host cells.
AB  - In this study, we utilized recombinant strains expressing the M5 and M18 proteins
      and M- mutants of group A streptococci to compare the abilities of these M
      proteins to confer resistance to phagocytosis and to mediate adhesion to host
      cells. The data indicate that the M5 and M18 proteins can confer resistance to
      phagocytosis, that fibrinogen is required for this resistance, and that these M
      proteins can mediate adhesion to HEp-2 cells.

PMID- 9169795
TI  - The lipopolysaccharide O side chain of Vibrio vulnificus serogroup E is a
      virulence determinant for eels.
AB  - Vibrio vulnificus is a gram-negative bacterium capable of producing septicemic
      infections in eels and immunocompromised humans. Two biotypes are classically
      recognized, with the virulence for eels being specific to strains belonging to
      biotype 2, which constitutes a homogeneous lipopolysaccharide (LPS)-based O
      serogroup (which we have designated serogroup E). In the present study we
      demonstrated that the O side chain of this LPS determines the selective virulence
      of biotype 2 for eels: (i) biotype 1 strains (which do not belong to serogroup E)
      are destroyed by the bactericidal action of nonimmune eel serum (NIS) through
      activation of the alternative pathway of complement, (ii) biotype 2 strains (of
      serogroup E) are resistant to NIS, and (iii) rough mutants of biotype 2 lacking
      the O polysaccharide side chain are sensitive to NIS and avirulent for eels.

PMID- 9169796
TI  - Binding of Helicobacter pylori to sialic acid-containing glycolipids of various
      origins separated on thin-layer chromatograms.
AB  - Two standard strains of Helicobacter pylori, grown on solid or in liquid medium,
      were studied for their binding to sialic acid-containing glycosphingolipids on
      thin-layer plates. NCTC 11637, but not strain 11638, bound to mixtures of
      gangliosides of various human and animal origins with similar binding patterns
      and also to polyglycosylceramides of human erythrocytes, leukocytes, and
      placenta. There was an apparent specificity for NeuAc alpha3Gal of the neolacto
      series of gangliosides, since NeuAc alpha6Gal or ganglio-series gangliosides did
      not bind.

PMID- 9169797
TI  - Modulation of neutrophil superoxide response and intracellular diacylglyceride
      levels by the bacterial pigment pyocyanin.
AB  - Low concentrations of pyocyanin are reported to enhance superoxide production by
      human neutrophils exposed to various stimuli, yet the mechanism remains unknown.
      Using lucigenin-enhanced chemiluminescence, we examined the kinetics of the
      neutrophil superoxide response in the presence of pyocyanin. At all
      concentrations (12.5 to 200 microM), pyocyanin decreased the peak superoxide
      response while prolonging the duration of the response. The prolonged response
      may be associated with an observed increase in intracellular diacylglyceride
      levels due to pyocyanin exposure.

PMID- 9169798
TI  - Expression of the Streptococcus mutans fructosyltransferase gene within a
      mammalian host.
AB  - In vivo expression of the virulence-associated fructosyltransferase gene (ftf) of
      Streptococcus mutans has been examined. S. mutans ftf expression is affected by
      both the specific carbohydrate consumed and the age of the host animal.

PMID- 9169799
TI  - Identification and characterization of a DNA region involved in the export of
      capsular polysaccharide by Actinobacillus pleuropneumoniae serotype 5a.
AB  - Actinobacillus pleuropneumoniae synthesizes a serotype-specific capsular
      polysaccharide that acts as a protective barrier to phagocytosis and complement
      mediated killing. To begin understanding the role of A. pleuropneumoniae capsule
      in virulence, we sought to identify the genes involved in capsular polysaccharide
      export and biosynthesis. A 5.3-kb XbaI fragment of A. pleuropneumoniae serotype
      5a J45 genomic DNA that hybridized with DNA probes specific for the Haemophilus
      influenzae type b cap export region was cloned and sequenced. This A.
      pleuropneumoniae DNA fragment encoded four open reading frames, designated
      cpxDCBA. The nucleotide and predicted amino acid sequences of cpxDCBA contained a
      high degree of homology to the capsule export genes of H. influenzae type b
      bexDCBA, Neisseria meningitidis group B ctrABCD, and, to a lesser extent,
      Escherichia coli K1 and K5 kpsE and kpsMT. When present in trans, the cpxDCBA
      gene cluster complemented kpsM::TnphoA or kpsT::TnphoA mutations, determined by
      enzyme immunoassay and by restored sensitivity to a K5-specific bacteriophage. A
      cpxCB probe hybridized to genomic DNA from all A. pleuropneumoniae serotypes
      tested, indicating that this DNA was conserved among serotypes. These data
      suggest that A. pleuropneumoniae produces a group II family capsule similar to
      those of related mucosal pathogens.

PMID- 9169800
TI  - Analysis of the Legionella pneumophila fliI gene: intracellular growth of a
      defined mutant defective for flagellum biosynthesis.
AB  - Using a PCR-based strategy and degenerate oligonucleotides, we isolated a
      Legionella pneumophila gene that showed high sequence similarity to members of
      the fliI gene family. An insertion mutation that disrupted the fliI open reading
      frame was recombined onto the L. pneumophila chromosome and analyzed for its
      effects on production of flagella and intracellular growth. The mutation resulted
      in loss of surface-localized flagellin protein but had no effect on the ability
      of the bacteria to grow within cultured cells. Therefore, in spite of the fact
      that some aflagellar mutations render L. pneumophila unable to grow within
      macrophages, the isolation of this defined mutant confirms that production of
      flagella is not required for intracellular growth.

PMID- 9169802
TI  - Current and future therapy of nasopharyngeal cancer.

PMID- 9169801
TI  - Oral immunization of mice with attenuated Salmonella typhimurium aroA expressing
      a recombinant Mycoplasma hyopneumoniae antigen (NrdF).
AB  - Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia,
      a commercially expensive respiratory disease of swine. Salmonella typhimurium
      SL3261 was used as a live carrier of plasmid pKF1, which encodes a 15-kDa
      recombinant M. hyopneumoniae protein. This expressed recombinant protein consists
      of the carboxy-terminal 11 kDa of a 42-kDa M. hyopneumoniae NrdF ribonucleotide
      reductase R2 subunit protein. Rabbit anti-15-kDa serum was able to inhibit the
      growth of viable M. hyopneumoniae J in vitro. When used as a live oral vaccine,
      S. typhimurium SL3261(pKF1) induced a significant secretory immunoglobulin A
      immune response in the lungs of mice orally immunized against the M.
      hyopneumoniae antigen. Utilization of live oral vaccines expressing potentially
      protective M. hyopneumoniae proteins, such as the NrdF antigen, which can
      stimulate a lung mucosal response against surface-accessible proteins may provide
      a cost-effective alternative to the present control strategies used for porcine
      enzootic pneumonia.

PMID- 9169803
TI  - Prognostic factors in adult soft-tissue sarcomas of the head and neck.
AB  - PURPOSE: The main objectives of this study were (a) to review the treatment
      results of primary head and neck soft-tissue sarcoma at our institution, (b) to
      identify important prognostic factors in local control and survival, and (c) to
      assess the efficacy of salvage therapy. METHODS AND MATERIALS: Sixty-five
      patients were treated at the University of California, San Francisco, between
      1961 and 1993. Seventeen patients (27%) had low-grade, 10 (15%) had intermediate
      grade, and 38 (58%) had high-grade sarcomas. Tumors were > 5 cm in 35 patients.
      Local management consisted of surgery alone in 14 patients (22%), surgery and
      radiotherapy in 40 (61%), and radiotherapy alone in 11 (17%) patients. The median
      follow-up was 64 months. RESULTS: The 5-year actuarial local control rate of the
      entire group was 66%. Tumor size and grade were important predictors for local
      control on multivariate analysis. The actuarial local control rate at 5 years was
      92% for T1 vs. 40% for T2 primaries (p = 0.004), and 80% for Grade 1-2 vs. 48%
      for Grade 3 tumors (p = 0.01). None of the patients treated with radiotherapy
      alone with a dose of 50-65 Gy were controlled locally. Combined radiotherapy and
      surgery appeared to yield superior local control compared to surgery alone (77%
      vs. 59%); however, the difference was not statistically significant. The 5-year
      actuarial overall and cause-specific survivals were 56% and 60%, respectively.
      Unfavorable prognostic factors for cause-specific survival on multivariate
      analysis were age > 55 (p = 0.009), high tumor grade (p = 0.0002), inadequate
      surgery (p = 0.008), and positive surgical margins (p = 0.0009). In patients who
      underwent salvage therapy for treatment failure, the 5-year actuarial survival
      after salvage treatment was 26%. CONCLUSION: Tumor size and grade were important
      predictors for local control. Age, grade, adequacy of surgery, and status of
      surgical margins were significant prognostic factors for survival. There was a
      trend of improved local control with combined surgery and radiotherapy compared
      to either modality alone for high-risk patients. Radiotherapy alone with doses <
      or = 65 Gy was insufficient for control of gross disease. Aggressive salvage
      therapy was worthwhile in patients whose disease was uncontrolled after the
      initial treatment.

PMID- 9169804
TI  - Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of local
      and regional control.
AB  - PURPOSE: This retrospective study was conducted to review the results of
      treatment and to identify prognostic factors for local and regional control in a
      population of 378 patients with nasopharyngeal carcinomas treated in a single
      institution by radiation therapy alone. METHODS AND MATERIAL: All patients were
      treated at The University of Texas M. D. Anderson Cancer Center between 1954 and
      1992 following a consistent treatment philosophy but with evolving technique.
      There were 286 males and 92 females with a median age of 52 years (range: 16-86
      years). The majority of the patients were Caucasian (282 patients, 75%). Thirty
      two patients (8%) had one or more cranial nerve deficits. Three-fourths of the
      patients presented with AJCC Stage IV disease (T4, N0-3, 118 patients; T1-3, N2-3
      164 patients). Histologically, 193 tumors (51%) were squamous cell carcinomas,
      154 (41%) lymphoepitheliomas, and 31 (8%) unclassified carcinomas. Average total
      dose varied with T-stage and ranged from 60.2 to 72.0 Gy. Median follow-up time
      was 10 years. RESULTS: For the entire population the 5-, 10-, and 20-year
      actuarial survival rates were 48, 34, and 18%, respectively, with 184 patients
      (49%) dying of nasopharyngeal cancer. Actuarial control rates at 5, 10, and 20
      years were 71, 66, and 66% for the primary site and 84, 83, and 83% for the neck.
      A total of 100 patients (26%) had local failures and 51 patients (13%) had
      regional failures with a median time to recurrence of 8.2 months and 13 months,
      respectively. Advanced T-stage, squamous histology, and presence of cranial nerve
      deficits were poor prognostic factors for local control in both univariate and
      multivariate analyses. N-stage and tumor histology were significant factors for
      neck control. Treatment year, total dose within the ranges used, and duration of
      treatment did not have any significant effect on local or regional control. The
      actuarial incidence of Grade 3-5 late complications was 16, 19, and 29% at 5, 10,
      and 20 years, respectively. Twelve patients (3%) died of treatment-related
      complications; all but one fatal complication occurred before 1971 and the other
      in 1976. CONCLUSIONS: This study shows very good long-term local and regional
      control rates for nasopharyngeal carcinomas after definitive radiotherapy and
      establishes a benchmark for newer treatment strategies. Improvements in treatment
      technique over the years have dramatically reduced the frequency of severe late
      complications. Patients with advanced stage tumors and differentiated squamous
      histology have a relatively poor prognosis when treated with conventional
      radiotherapy and are candidates for dose escalation or combined modality studies.

PMID- 9169805
TI  - Radiosurgery for skull base malignancies and nasopharyngeal carcinoma.
AB  - PURPOSE: Patients with skull base lesions present a challenging management
      problem because of intractable symptoms and limited therapeutic options. In 1989
      we began treating selected patients with skull base lesions using linac
      stereotactic radiosurgery. In this study the efficacy and toxicity of this
      therapeutic modality is investigated. METHODS AND MATERIALS: Forty-seven patients
      with 59 malignant skull base lesions were treated with linac radiosurgery between
      1989 and 1995. Eleven patients were treated for primary nasopharyngeal carcinoma
      using radiosurgery as a boost (7 Gy-16 Gy, median: 12 Gy) to the nasopharynx
      after a course of fractionated radiotherapy (64.8-70 Gy) without chemotherapy.
      Another 37 patients were treated for 48 skull base metastases or local
      recurrences from primary head and neck cancers. Eight of these patients had 12
      locally recurrent nasopharyngeal carcinoma lesions occuring 6-96 months after
      standard radiotherapy, including one patient with nasopharyngeal carcinoma who
      developed a regional relapse after radiotherapy with a stereotactic boost. Lesion
      volumes by CT or MRI ranged from 0 to 51 cc (median: 8 cc). Radiation doses of
      7.0 Gy-35.0 Gy (median: 20.0 Gy) were delivered to recurrent lesions, usually as
      a single fraction. RESULTS: All 11 patients who received radiosurgery as a
      nasopharyngeal boost after standard fractionated radiotherapy remain locally
      controlled (follow-up: 2-34 months, median: 18). However, one patient required a
      second radiosurgical treatment for regional relapse outside the initial
      radiosurgery volume. Thirty-three of 48 (69%) recurrent/metastatic lesions have
      been locally controlled, including 7 of 12 locally recurrent nasopharyngeal
      lesions. Follow-up for all patients with recurrent lesions ranged from 1 to 60
      months (median: 9 months). Local control did not correlate with lesion size (p =
      0.80), histology (p = 0.78), or radiosurgical dose (p = 0.44). Major
      complications developed after 5 of 59 treatments (8.4%), including three cranial
      nerve palsies, one CSF leak, and one trismus. Complications were not correlated
      with radiosurgical volume (p = 0.20), prior skull base irradiation (p = 0.90), or
      radiosurgery dose > 20 Gy (p = 0.49). CONCLUSION: Stereotactic radiosurgery is a
      reasonable treatment modality for patients with skull base malignancies,
      including patients with primary and recurrent nasopharyngeal carcinoma. The dose
      distribution obtained with stereotactic radiosurgery provides better homogeneity
      than an intracavitary implant when used as a boost for nasopharyngeal lesions,
      especially lesions which involve areas distant to the nasopharyngeal mucosa.

PMID- 9169806
TI  - Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF)
      on the frequency and severity of radiation mucositis in patients with head and
      neck carcinoma.
AB  - PURPOSE: Based on the clinical evidence of mucosal protection by GM-CSF during
      cytotoxic chemotherapy, a pilot study was undertaken to determine the safety and
      mucosal reaction of patients receiving GM-CSF while undergoing definitive
      conventional fractionated radiotherapy in head and neck carcinoma. METHODS AND
      MATERIALS: Patients were considered eligible if buccal mucosa and oropharynx were
      included in the teleradiation field. Ten adult patients with squamous cell
      carcinoma of head and neck (buccal mucosa--8 and posterior 1/3 tongue--2) were
      entered into the trial. Radiation therapy was delivered with telecobalt machine
      at conventional 2 Gy fraction and 5 fractions/week. The radiation portals
      consisted of two parallel opposing lateral fields. GM-CSF was given
      subcutaneously at a dose of 1 microg/kg body weight, daily, after 20 Gy until the
      completion of radiation therapy. Patients were evaluated daily for mucosal
      reaction, pain, and functional impairment. RESULTS: The median radiation dose was
      66 Gy. Eight patients received > or = 60 Gy. The tolerance to GM-CSF was good.
      All 10 patients completed the planned daily dose of GM-CSF without interruption.
      Mucosal toxicity was Grade I in four patients till the completion of radiotherapy
      (dose range 50-66 Gy). Six patients developed Grade II reaction, fibrinous
      mucosal lesions of maximum size 1.0-1.5 cm, during radiotherapy. None developed
      Grade III mucositis. The maximum mucosal pain was Grade I during GM-CSF therapy.
      In two patients after starting GM-CSF the pain reduced in intensity. Functional
      impairment was mild to moderate. All patients were able to maintain adequate oral
      intake during the treatment period. Total regression of mucosal reaction occured
      within 8 days following completion of radiotherapy. CONCLUSIONS: GM-CSF
      administration concurrently with conventional fractionated radiotherapy was
      feasible without significant toxicity. The acute side effects of radiotherapy
      namely mucositis, pain, and functional impairment were nil to minimal. The
      results are suggestive of mucosal protection by GM-CSF during radiotherapy and
      warrants further study in randomized double blind trial.

PMID- 9169807
TI  - Can pretreatment computed tomography predict local control in T3 squamous cell
      carcinoma of the glottic larynx treated with definitive radiotherapy?
AB  - PURPOSE: To determine if pretreatment computed tomography (CT) can predict local
      control in T3 squamous cell carcinoma of the glottic larynx treated with
      definitive radiotherapy (RT). METHODS AND MATERIALS: Forty-two patients with
      previously untreated T3 squamous cell carcinoma of the glottic larynx were
      treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes
      and extent were determined by consensus of two head and neck radiologists on
      pretreatment CT studies. A tumor score was calculated and assigned to each
      primary lesion depending on the extent of laryngeal spread. Sclerosis of any
      laryngeal cartilage was recorded. The specific CT parameters assessed were
      correlated with local control. RESULTS: Tumor volume was a significant predictor
      of local control. For tumors measuring < 3.5 cm3, local control was achieved in
      22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was
      achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity
      using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of
      anatomic extent was also found to be a significant predictor of local control.
      The local control rate for tumors assigned a low tumor score (< or = 5) was 78%
      (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6,
      7, or 8) (p = 0.008). A significant decrease in the local control rate was
      observed for cancers involving the paraglottic space at the false vocal cord
      level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of
      the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors
      involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020).
      There were 12 patients with sclerosis of both the ipsilateral arytenoid and the
      adjacent cricoid cartilage. These patients showed a significant decrease in local
      control (4 of 12 [33%]). CONCLUSION: Pretreatment CT can stratify patients with
      T3 glottic carcinoma into groups more or less likely to be locally controlled
      with definitive RT. The local control rate for these tumors can be improved using
      a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic
      larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage
      sclerosis.

PMID- 9169808
TI  - Dose estimation to critical organs from vertex field treatment of brain tumors.
AB  - PURPOSE: Radiation management of intracranial tumors may require a noncoplanar
      vertex field that often irradiates the entire length of the body. In view of
      radiation related risks to the normal tissues dose estimation to the extracranial
      organs such as the thyroid gland, spinal cord, heart, and genitalia is performed
      for a vertex field. METHODS AND MATERIALS: A vertex field used clinically was
      reproduced on an anthropomorphic Rando phantom to measure radiation dose to
      various organs in the primary beam. Three photon beams (4, 6, and 10 MV), and two
      high energy electron beams (16 and 20 MeV) were used. Dosimetry was performed
      with an ion chamber sandwiched between phantom slices at the appropriate
      positions. All doses were normalized to the target dose at a depth of 5 cm. The
      effect of the head position was studied by rotating the gantry angle up to +/-20
      degrees to mimic the extension and flexion of the head. Theoretical calculation
      was performed using an exponential best fit to the depth dose table to estimate
      the dose to various points and compare with the measured dose. RESULTS: The
      measured normalized dose to the cervical cord, thyroid, heart, and female and
      male gonads are 60, 36, 16, 2.5, and 1.6%, respectively, for a 6 MV photon beam.
      The dose from 4 MV and 10 MV are slightly lower and higher, respectively. Doses
      from electron beams are about a factor of 4-10 lower than those of the photon
      beams. The measured gonadal dose from the primary beam is <5% of the target dose
      for all energies used in the study. The actual value, however, is dependent on
      the body structure, length, and the posture of the patient. A +5 degree head
      flexion had little effect on the dose to the various parts of the body. The head
      rotations greater than +/-10 degrees produced relatively lower doses by a factor
      of 10(-2) to the organs at distances greater than 40 cm from the prescription
      point. The radiation doses to the different critical organs estimated from the
      fitted curves are lower than the measured doses up to 35%. CONCLUSIONS: When a
      vertex field is used for the treatment of the brain tumors, the entire axial
      length of the body is irradiated which adds to the integral dose. Unlike the
      scattered and leakage radiation, the primary dose to extracranial critical organs
      is greater for higher energies. For a 10 MV beam the ovary and testis at a
      distance of 80 cm and 90 cm may receive a dose of 4.2 and 3%, respectively, of
      the target dose. The gonadal dose could be quite significant if the entire
      treatment is delivered using a vertex field. For pediatric and smaller patients,
      dose to the critical organs at known distances could be estimated from the
      empirical equation obtained from the measured data. While the risk-benefit ratio
      is often evaluated and acceptable for treating malignant tumors, the long-term
      complications need thorough assessment in younger and curable patients. In view
      of radiation carcinogenesis and genetic burden, dose reduction to critical organs
      should be considered using a 3D planning system to arrange beams in other
      nonaxial planes and by considering electron beams for the vertex field.

PMID- 9169809
TI  - Symptom resolution, tumor control, and side effects following postoperative
      radiotherapy for pituitary macroadenomas.
AB  - This study reports the outcome of 70 patients who were treated by a consistent
      treatment plan of surgery and postoperative radiotherapy (RT) for pituitary
      macroadenomas in the modern era [computed tomographic scan or magnetic resonance
      imaging (MRI), dopamine agonist therapy (DA) added as indicated, and
      immunohistochemical staining]. Sixty-two patients underwent transsphenoidal
      surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions
      postoperatively (vs. other dose fractionation schemes). Twenty-four patients
      received DA for prolactin-secreting tumors. With a median follow-up of 8 years
      (range 2-15), 68 patients have experienced continuous control of their tumors.
      Most symptoms related to mass effect abated, while physiologic symptoms such as
      amenorrhea from markedly elevated prolactin levels tended to persist. Treatment
      induced hypopituitarism occurred in 42% of the patients at risk. No patients in
      this series have died as a result of their pituitary tumor. No gross
      neuropsychologic dysfunction after treatment has been noted. While it is possible
      at this time with serial MRI to withhold postoperative RT and observe some
      patients who have had a "gross total" resection of a macroadenoma, the
      therapeutic ratio for surgery and adjuvant radiotherapy for patients with
      nonfunctional tumors as well as select patients with secretory macroadenomas is
      favorable.

PMID- 9169810
TI  - Consensus statement: guidelines for PSA following radiation therapy. American
      Society for Therapeutic Radiology and Oncology Consensus Panel.

PMID- 9169811
TI  - Stage T1-2 prostate cancer: a multivariate analysis of factors affecting
      biochemical and clinical failures after radical prostatectomy.
AB  - PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection
      and outcome evaluation after treatment of clinically localized prostate cancer.
      Careful case selection can have a profound impact on pathologic findings and
      ultimate outcome. In addition, salvage treatment is frequently initiated at the
      time of biochemical relapse rather than clinical recurrence. Consequently,
      patterns of failure can be significantly altered compared to previous times when
      PSA was not available. To better understand the impact of PSA on pathologic
      findings, outcome, and salvage treatment, we reviewed our experience in the PSA
      era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy.
      METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with
      clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The
      distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml
      (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%).
      The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen
      patients received adjuvant or neoadjuvant androgen suppression and 13 received
      postoperative radiotherapy. Only 31 patients (7%) had pathologically positive
      pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three
      percent of patients had surgical Gleason scores > or = 7, and 65% had
      extracapsular extension. The median follow-up time was 41 months. RESULTS: The
      projected overall survival at 7 years after surgery was 90%. The 5-year clinical
      relapse-free survival rate was 84%. At 5 years, the local control and distant
      failure rates were 92% and 91%, respectively. Biochemical relapse was defined as
      a detectable or rising PSA level after prostatectomy. The 5-year biochemical
      relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients
      with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for >
      20. Combining the two independent preoperative variables, iPSA and biopsy GS
      (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or =
      10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7).
      The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases
      (p < 0.001). On multivariate analysis, three factors independently predicted
      biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical
      specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5
      year bRFS rates for margin positive vs. margin negative patients were 37% vs.
      78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42%
      vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA.
      In patients who manifested biochemical failure followed by a clinical failure,
      the median interval between the PSA rise and clinical failure was 19 months
      (range 7-71). Margin involvement was the only independent predictor of local
      failure (p = 0.019). The 5-year local failure-free survival for negative margin
      cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN)
      involvement and high-risk group were the two independent predictors of distant
      failure. The 5-year distant failure-free survival for negative LN cases was 94%
      vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free
      survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For
      the 124 patients failing biochemically, 85 were observed and 39 were treated
      either with radiation or androgen deprivation. With a median follow-up of 32
      months, the clinical disease relapse-free survival was 79% for the treated
      patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION:
      Pretreatment PSA is the most potent clinical factor independently predicting
      biochemical relapse, thereby allowing markedly better case selection. Achieving
      negative margins, even in relatively advanced disease, provides excellent lon

PMID- 9169812
TI  - Equivalent biochemical failure-free survival after external beam radiation
      therapy or radical prostatectomy in patients with a pretreatment prostate
      specific antigen of > 4-20 ng/ml.
AB  - PURPOSE: Biochemical failure-free survival stratified by the pretreatment
      prostate-specific antigen (PSA) and biopsy Gleason score (bGl) is determined for
      prostate cancer patients managed definitively with external beam radiation
      therapy or radical retropubic prostatectomy. METHODS AND MATERIALS: A Cox
      regression multivariable analysis evaluating the variables of PSA, bGl, and
      clinical stage was used to evaluate the end point of time to PSA failure in 867
      and 757 consecutive prostate cancer patients managed definitively with external
      beam radiation therapy or radical retropubic prostatectomy, respectively. PSA
      failure-free survival was determined using Kaplan-Meier analysis. Comparisons
      were made using the log rank test. RESULTS: The pretreatment PSA, bGl, and
      clinical stage (T3,4 vs. T1,T2) were found to be independent predictors of time
      to post-treatment PSA failure for both surgically and radiation managed patients
      using Cox regression multivariable analysis. Patients with a pretreatment PSA of
      > 4 ng/ml and < or = 20 ng/ml could be classified into risk groups for time to
      post-therapy PSA failure: low = PSA > 4-10 ng/ml and bGl < or = 4; intermediate =
      PSA > 4-10 and bGl 5-7; or PSA > 10-20 ng/ml and bGl < or = 7; high = PSA > 4-20
      ng/ml and bGl > or = 8. Two-year PSA failure-free survival for surgically managed
      and radiation-managed patients, respectively, were 98% vs. 92% (p = 0.45), 77%
      vs. 81% (p = 0.86), and 51% vs. 53% (p = 0.48) for patients at low, intermediate,
      and high risk for post-therapy PSA failure. CONCLUSIONS: There was no statistical
      difference in the 2-year PSA failure-free survival for potentially curable
      patients managed definitively with surgery or radiation therapy when a
      retrospective comparison stratifying for the pretreatment PSA and bGl was
      performed.

PMID- 9169814
TI  - Cell kinetic measurements in prostate cancer.
AB  - PURPOSE: Two approaches have been suggested for escalating the total dose in
      radiotherapy treatment of prostate cancer. One is conformal radiotherapy; the
      other is hyperfractionation using many small fractions. Both imply some possible
      prolongation in overall treatment time. To judge whether prolonged treatment
      schedules would be detrimental, it is necessary to know the proliferation rates
      in human prostate tumors, specifically, the potential doubling time (Tpot). There
      is a lack of data on this parameter in the literature. METHODS AND MATERIALS:
      Seven patients with adenocarcinoma of the prostate were studied. A tracer dose of
      100 mg/m2 of IUdR was infused intravenously 4-12 h before biopies were taken.
      Biopsies were fixed in 70% ethanol, stored at 4 degrees C, and later prepared and
      stained by standard methods for flow cytometry, using the red fluorescence signal
      for DNA and the green fluorescence signal (fluorescein isothiocyanate) for 5-iodo
      2'-deoxyuridine. The duration of DNA synthesis (Ts) was determined by the
      relative movement (RM) method, knowing the interval between tracer administration
      and biopsy. Tpot was calculated as the quotient of Ts by labeling index (LI).
      RESULTS: In two of the seven tumors the LI was too low (<0.6%) for a reliable
      estimate of RM to be made, so no determination of Tpot was possible for these
      tumors. The mean LI values in the other five tumors were 2.4%, 1.4%, 1.0%, 3.0%,
      and 0.9%. The durations of Ts were 13.2, 9.5, 10.0, 11.7, and 12.7 h,
      respectively. The resulting values of Tpot were 23, 28, 42, 16, and 61 days,
      respectively. CONCLUSION: The low labeling indices in prostate tumors, also
      reported by others, made estimation of Ts by RM impossible in about a third of
      these tumors. However, five tumors yielded long estimates for Tpot, implying that
      prolongation from 6 to about 8 weeks should not be detrimental.

PMID- 9169813
TI  - Combined external beam irradiation and external regional hyperthermia for locally
      advanced adenocarcinoma of the prostate.
AB  - PURPOSE: To determine the safety and efficacy of combined external beam
      irradiation and external regional hyperthermia in the treatment of adenocarcinoma
      of the prostate. METHODS AND MATERIALS: From 1987 to 1994, 30 patients received
      combined external beam irradiation and external regional hyperthermia for locally
      advanced prostate cancer. The results of the 21 patients with newly diagnosed (n
      = 18) or locally recurrent (n = 3) adenocarcinoma are reported herein. No patient
      had evidence of distant metastases. Total radiotherapy doses of 65-70 Gy to the
      prostate were planned using a four-field box technique. Hyperthermia treatments
      were delivered using an annular phased array microwave device. The treatment goal
      was to achieve temperatures > or = 42 degrees C in all measured points within the
      prostate. RESULTS: Of the newly diagnosed patients, 16 out of 18 (89%) had T3 or
      T4 tumors, 11 out of 18 (61%) had Gleason scores of 7-9, and the mean
      pretreatment Prostate Specific Antigen (PSA) was 69 ng/ml. The median follow-up
      of all 21 patients was 36 months. None of the patients achieved the treatment
      goal of all intratumoral temperatures > or = 42 degrees C. The mean CEM 43 T90
      was 2.34 min. The disease-free survival at 36 months is 25%; 12 out of 18 (67%)
      of the patients have relapsed. The only significant predictor of relapse was
      pretreatment PSA. There were no complications > Grade 3. CONCLUSIONS: In spite of
      the inability to achieve high tumor temperatures, the relapse-free survival rate
      in this population of patients with very advanced localized prostate cancer
      treated with radiation therapy plus hyperthermia compares favorably with most
      series using radiation therapy alone. Further studies aimed at improving the
      ability to deliver hyperthermia to the prostate are warranted.

PMID- 9169815
TI  - Analysis of prognostic factors in stage IIB-IVA cervical carcinoma treated with
      radiation therapy: value of computed tomography.
AB  - PURPOSE: To define the influence of the tumor size measured by computed
      tomography (CT) and lymph node involvement detected by CT in patients treated
      with radiation therapy for Stage IIB-IVA carcinoma of intact uterine cervix.
      METHODS AND MATERIALS: This was a retrospective analysis of 233 patients with
      uterine cervical cancer managed with both external irradiation and high-dose-rate
      intracavitary brachytherapy (HDR-ICR) at Kanagawa Cancer Center. The results were
      analyzed for the end points of absolute survival (AS), disease-free survival
      (DFS), pelvic control (PC), and central control (CC). The parameters of stage, CT
      measured anterior-posterior (AP) cervix size, and CT-detected lymph node
      metastases were evaluated using univariate and multivariate analysis. RESULTS:
      The stage, AP cervix size, and lymph node involvement were significant
      pretreatment factors in univariate analysis with respect to AS, DFS, PC, and CC.
      Multivariate analysis confirmed that significant risk was associated with certain
      prognostic parameters. Those in terms of AS, in order of decreasing significance,
      were lymph node involvement, AP cervix size, age, and total HDR-ICR dose. When
      DFS was studied, lymph node involvement and AP cervix size were demonstrated to
      have a significant effect. Stage and lymph node involvement significantly
      affected PC. CONCLUSION: Because the International Federation of Gynecological
      Obstetrics staging system fails to incorporate important prognostic information
      about tumor volume and lymph node involvement, CT-detected lymph node metastases
      as well as CT-measured cervix size should be determined as complementary
      additional prognostic measures.

PMID- 9169816
TI  - Dose escalation for non-small cell lung cancer using conformal radiation therapy.
AB  - PURPOSE: Improved local control of non-small cell lung cancer (NSCLC) may be
      possible with an increased dose of radiation. Three-dimensional radiation
      treatment planning (3D RTP) was used to design a radiation therapy (RT) dose
      escalation trial, where the dose was determined by (a) the effective volume of
      normal lung irradiated, and (b) the estimated risk of a complication. Preliminary
      results of this trial were reviewed. METHODS AND MATERIALS: A graph of the iso
      normal tissue complication probability (NTCP) levels associated with a dose and
      effective volume (V(eff)) was derived, using normal tissue parameters derived
      from the literature. This led to a dose escalation schema, where patients were
      sorted into 1 of 5 treatment bins, determined by the V(eff) of the best possible
      treatment plan. The starting doses ranged from 63 to 84 Gy. Each treatment bin
      was then escalated separately, as in Phase I dose escalation fashion, with Grade
      > or = 3 radiation pneumonitis defined as dose limiting. To allow for dose
      escalation, we required patient follow-up to be > or = 6 months for at least
      three patients. 3D treatment planning was used to irradiate only the
      radiographically abnormal areas, with 2.1 Gy (corrected for lung
      inhomogeneity)/day. Clinically uninvolved lymph nodes were not treated
      prophylactically. RESULTS: A total of 48 NSCLC patients have been treated (Stage
      I/II: 18 patients; Stage III: 28 patients; mediastinal recurrence postsurgery: 2
      patients). No radiation pneumonitis has been observed in the 30 patients
      currently evaluable beyond the 6-month time point. All treatment bins have been
      escalated at least once. Current doses in the five treatment bins are 69.3, 69.3,
      75.6, 84, and 92.4 Gy. None of the 15 evaluable patients in any bin with > or =
      30% NTCP experienced clinical radiation pneumonitis, implying that the actual
      risk is < 20% (beta error rate 5%). Despite the observation of the clinically
      negative lymph nodes at high risk, there has been no failure in the untreated
      mediastinum as the sole site of first failure. Three of 10 patients receiving >
      or = 84 Gy have had biopsy proven residual or locally recurrent disease.
      CONCLUSION: Successful dose escalation in a volume-dependent organ can be
      performed using this technique. By incorporating the effective volume of
      irradiated tissue, some patients have been treated to a total dose of radiation
      over 50% higher than traditional doses. The literature-derived parameters appear
      to overestimate pneumonitis risk with higher volumes. There has been no obvious
      negative effect due to exclusion of elective lymph node radiation. When
      completed, this trial will have determined the maximum tolerable dose of RT as a
      single agent for NSCLC and the appropriate dose for Phase II investigation.

PMID- 9169817
TI  - Localized primary malignant lymphoma of bone.
AB  - PURPOSE: A single institution's experience with the treatment of localized
      primary malignant lymphoma of bone (PLB) was analyzed to identify major
      prognostic factors, toxicity, and optimal treatment for this rare malignancy.
      METHODS AND MATERIALS: A retrospective analysis of 45 previously untreated
      patients with Ann Arbor stage IE and IIE PLB from 1967 to 1992 was undertaken.
      All histopathologic material was reviewed. Irradiated patients received at least
      40 Gy. Systemic chemotherapy was generally doxorubicin based. Overall survival
      (OS), progression free survival (PFS), and disease-specific survival (DSS) were
      calculated actuarially. RESULTS: Histologically, there were 41 diffuse large
      cell, 2 diffuse mixed cell, 1 lymphocytic, and 1 lymphoblastic lymphomas.
      International Index scores were assessed on 43 patients. Thirty-six patients were
      treated with chemotherapy and radiation (CMT), five patients were treated with
      radiation only, and four patients were treated with chemotherapy only. Univariate
      analysis revealed significantly improved 5-year OS for those patients who had
      International Index scores of 0 vs. scores of 1 or 2 (85 vs. 53%, respectively, p
      = 0.004). Analysis failed to demonstrate a difference in OS, PFS, or DSS when
      comparing radiotherapy alone versus CMT, stage IE vs. stage IIE, or axial
      skeleton involvement vs. extremities. CONCLUSION: The outcome of patients with
      PLB is relatively favorable in the era of CMT. Doses of radiation in the range of
      46 Gy provide optimal local control with an acceptable rate of complications. The
      International Index is a valid prognostic tool for PLB.

PMID- 9169818
TI  - Is machine energy (4-8 MV) associated with outcome for stage I-II breast cancer
      patients?
AB  - PURPOSE: To assess the relationship between machine energy (4-8 MV) and treatment
      outcome in patients treated with conservative surgery and radiation therapy.
      METHODS AND MATERIALS: Between 1968 and 1985, 1624 patients were treated for
      clinical Stage I or II invasive breast cancer. The study population was limited
      to 1380 patients who underwent complete gross excision and received greater than
      or equal to 60 Gy to the tumor bed. Of these, 1125 were treated on a 4 MV, 153 on
      a 6 MV, and 102 on an 8 MV linear accelerator. Patients were selected for
      treatment on the 8 MV machine based on chest wall separations greater than 24 cm.
      Of patients treated on the 8 MV, netting was used for 42% and bolus was used for
      26%. The median dose with bolus was 14 Gy in seven fractions (range: 2-34.2 Gy).
      Patients treated on the 8 MV accelerator were older, had a higher percentage of
      clinical T2 tumors, a higher percentage of pathologically positive nodes, and a
      lower incidence of extensive intraductal component (EIC). Median follow-up times
      were 130, 153, and 102 months, respectively, for survivors treated on the 4, 6,
      and 8 MV machines. RESULTS: We analyzed the site and 5-year crude incidence of
      first failure by machine energy and found the pattern of first failure site
      (local, nodal, or distant) to be virtually identical for each energy group. Of
      the local failures, 12 were in the skin of the treated breast, and these failures
      were evenly distributed by machine energy. We performed a multivariate analysis
      to adjust for factors known to predict for treatment failure. When adjusted for
      these other variables, machine energy was not associated with an increased (or
      decreased) risk of recurrence (RR for 8 MV vs. 4 MV = 0.94, p = 0.7; RR for 6 MV
      vs. 4 MV = 1.0, p = 0.9). We also analyzed the nature and incidence of treatment
      complications (rib fracture, radiation pneumonitis, soft tissue necrosis, and
      brachial plexopathy) and found no significant differences among the three
      treatment groups when stratified by treatment technique (tangents only vs. three
      field). There was also no significant difference in cosmetic outcome at 5 years
      among the three groups. CONCLUSIONS: We conclude that machine energy over the
      range of 4 to 8 MV does not significantly affect treatment outcome. Specifically,
      it was feasible to treat patients with large chest wall separations using an 8 MV
      machine without an increase in skin recurrences and with the improved dose
      homogeneity afforded by 8 MV machines as compared with those of lower energies.

PMID- 9169819
TI  - Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients
      with carcinoma of the anal canal.
AB  - PURPOSE: To determine the efficacy and tolerance of a standardized protocol of
      chemotherapy and low-dose radiotherapy in the treatment of anal cancer in human
      immunodeficiency virus (HIV)-infected patients. METHODS AND MATERIALS: Between
      1987 and 1995, eight HIV-positive patients with squamous cell carcinoma of the
      anal canal, four of whom had acquired immunodeficiency syndrome (AIDS), received
      therapy at the Kaiser Permanente Medical Center. All patients were treated using
      a combined modality approach consisting of low-dose radiotherapy (30 Gy in 15
      fractions delivered 5 days/week), and chemotherapy [1000 mg/m2 of 5-fluorouracil
      (5-FU) delivered on days 1-4 and 29-32 as a continuous infusion over 96 h, and 10
      mg/m2 of mitomycin C delivered as a bolus injection on day 1]. Patients have been
      followed from 4 to 81 months (mean 41, median 38). RESULTS: All eight patients
      completed the therapy with minor variations to the protocol, and all have
      attained a clinical complete response. Four patients are alive and free of
      disease, and four died as a result of complications of AIDS, but remained free of
      anal carcinoma. There were no mortalities from the protocol and the morbidity was
      acceptable. Only one patient each was noted to have Radiation Therapy Oncology
      Group/European Organization for Research and Treatment of Cancer Grade 4
      hematologic and gastrointestinal acute toxicity, and no Grade 4 skin toxicity was
      noted. CONCLUSION: This combined therapy is effective for HIV-infected patients
      and appears to be tolerable with acceptable toxicities. It is best applied to
      patients who are HIV positive, or who have AIDS without concurrent major
      opportunistic infections. This approach is reasonable and affords patients a
      reasonably good chance at sphincter preservation by avoiding abdominoperineal
      resection. The optimal therapy for HIV-positive patients with advanced AIDS
      remains less well defined.

PMID- 9169820
TI  - An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated
      radiotherapy of murine mammary carcinoma.
AB  - PURPOSE: TNP-470, a synthetic analogue of fumagillin which is a natural product
      of Aspergillus fumigatus, has been noted as an angiogenesis inhibitor. Combined
      effects of TNP-470 with fractionated radiotherapy (RT) were investigated using a
      mouse tumor. METHODS AND MATERIALS: Tumors were early generations of mammary
      carcinoma in C3H/He mice. Treatments were initiated when tumors reached an
      average diameter of 4-5 mm. Tumor response was evaluated by tumor growth (TG)
      time assay and 50% tumor control dose (TCD50) assay. Tumors were irradiated
      locally under hypoxic conditions or in air. Five fractionated radiation doses
      were given in the TG time assay, whereas a single dose or 10 fractionated doses
      were given in the TCD50 assay. TNP-470 (100 mg/kg) was administered
      subcutaneously twice a week during and/or after RT. RESULTS: In the TG time
      assay, significant delay of tumor growth was observed by TNP-470 alone (100 mg/kg
      x 2) compared with control tumors (p < 0.001), indicating that TNP-470 alone has
      an antitumor effect in vivo. When TNP-470 was administered during fractionated
      RT, no additional delay of tumor growth was observed. However, additive effects
      of TNP-470 was noted when it was given after the end of fractionated RT. In the
      TCD50 assay, no significant difference in TCD50s was observed between RT alone
      and RT combined with TNP-470 in single dose experiments. Hypoxic fraction of
      tumors calculated from the TCD50s was not affected significantly by
      administrating TNP-470 24 h before RT. On the other hand, in 10-fraction
      experiments, the TCD50 (RT with TNP-470, in air) was significantly higher than
      the TCD50 (RT alone, in air) (p < 0.005), indicating that TNP-470 given during
      fractionated RT decreased radiocurability. This negative effect of TNP-470 was
      not observed when TNP-470 was combined with fractionated RT given under hypoxic
      conditions. CONCLUSION: The tumor control probability decreased by administrating
      TNP-470 during fractionated RT in air. This unexpected result may be attributable
      to partial inhibition of reoxygenation by TNP-470, because no significant
      difference was noted between the TCD50 (RT with TNP-470) and the TCD50 (RT alone)
      under hypoxic conditions.

PMID- 9169821
TI  - Dynamics of tumor oxygenation, CD31 staining and transforming growth factor-beta
      levels after treatment with radiation or cyclophosphamide in the rat 13762
      mammary carcinoma.
AB  - PURPOSE: Tumors are dynamic tissues that undergo marked molecular, biochemical,
      and physiologic changes in response to cytotoxic anticancer therapies.
      Understanding the changes in tumor oxygenation and transforming growth factor
      beta expression may allow improved treatment regimens to be developed. METHODS
      AND MATERIALS: The effects of a single dose of radiation therapy (20 Gy) or a
      single dose of chemotherapy (cyclophosphamide, 250 mg/kg) on several molecular
      and physiologic parameters of the rat 13762 mammary carcinoma growing
      subcutaneously in female Fischer 344 rats were explored. RESULTS: Treatment of
      the tumor-bearing animals with 20 Gy of radiation killed about two logs (99%) of
      the 13762 tumor cells, and treatment with cyclophosphamide (250 mg/kg) killed
      about 1.5 logs (95%) of the 13762 tumor cells. Hypoxia, as determined by a pO2
      electrode, initially decreased in the tumors of treated animals until 6 h.
      posttreatment and then increased, so that 24 h. after administration of the
      radiation therapy or the chemotherapy the number of intratumoral vessels as
      determined by CD31 staining increased until about 24 h after cytotoxic therapy.
      Transforming growth factor-beta1, measured by radioimmunoassay, peaked in the
      serum between 6 h and 18 h and again between 72 h and 96 h after radiation
      therapy and peaked in the tumor at 24 h and again at 72 h after radiation
      therapy. The first serum peak after cyclophosphamide was 3 h after drug
      injection, with second peaks at 36 h and 48 h after drug administration. In the
      tumor, transforming growth factor-beta1 peaked between 6 h and 8 h after drug
      administration and again 36 h and 72 h after drug. Apoptosis was maximal 6 h
      after 20 Gy and 24 h after cyclophosphamide. Vascular endothelial growth factor
      was also increased in tumors after cytotoxic therapy. CONCLUSIONS: These changes
      in the tumor physiologic status are sufficient to protect the tumor from a second
      cytotoxic insult administered days afterwards and to result in a restructuring of
      the tissue.

PMID- 9169822
TI  - Specific response of mouse tumor-feeding arterioles to stimulation by 5-HT1
      agonists.
AB  - Using intravital microscopy, we compared the responses to 5-HT1 receptor
      stimulation by the host-modified arterioles feeding a Meth-A tumor implanted in
      the flank of female Balb/c mice with the responses of tumor-independent
      arterioles (TIA) and those of control arterioles from mice without tumor. Topical
      administration of 5 x 10(-5) M serotonin in the presence of 10(-4) M ketanserin
      (5-HT2 receptors inhibitor) induced arteriolar vasodilation in TIA (+13%) and in
      the control arterioles (+19%), but induced constriction (-14%) in the tumor
      feeding arterioles (TFA). Topical administration of the general 5-HT1 agonist 5
      carboxamidotryptamine maleate (10(-6) to 10(-4) M) or the 5-HT1A agonist
      buspirone (2 x 10(-6) to 2 x 10(-4) M) induced vasoconstriction that was
      dramatically higher in TFA than in TIA or control arterioles (p < 0.0001 in both
      cases). In addition, topical administration of the 5-HT1B agonist M
      trifluoromethylphenylpiperazine (2 x 10(-6) to 2 x 10(-4) M) produced opposite
      responses, i.e., dose-dependent vasodilation in TIA and control arterioles, and
      dose-dependent constriction in TFA. Since we observed the same degree of
      vasodilation in response to 10(-4) M acetylcholine in all three groups of
      arterioles, the differences between the responses to 5-HT1 receptor stimulation
      were not due to the absence of endothelial-dependent dilatory mechanisms in the
      tumor-feeding arterioles. We conclude that 5-HT1 agonists are interesting
      pharmacologic tools for the modulation of tumoral blood flow, since they more
      dramatically constrict the microvasculature feeding the tumors than that feeding
      normal tissue.

PMID- 9169823
TI  - Topoisomerase inhibition by lucanthone, an adjuvant in radiation therapy.
AB  - PURPOSE: To determine whether lucanthone can inhibit human topoisomerases in
      vitro. METHODS AND MATERIALS: Lucanthone was incubated with human topoisomerases
      II and I together with their plasmid substrates, to determine if lucanthone
      interfered with the catalytic activities of topoisomerases and if it enhanced the
      formation of DNA strand breaks, as determined by agarose gel electrophoresis of
      the resultant plasmid forms. RESULTS: Incubation of the enzymes with lucanthone
      inhibited the catalytic activity of topoisomerases II and I. With topoisomerase
      II, it increased the abundance of DNA double strand breaks (cleavable complexes).
      CONCLUSION: Lucanthone, like actinomycin D, inhibited topoisomerases II and I. It
      may act to enhance the yield of DNA double strand breaks in cells through a
      mechanism of topoisomerase II inhibition.

PMID- 9169824
TI  - Subadditive interaction of radiation and Taxol in vitro.
AB  - PURPOSE: To examine the dependency of Taxol-radiation interactions on the
      scheduling of the two agents. METHODS AND MATERIALS: The human laryngeal squamous
      cell carcinoma line SCC20 was used for this study. Cells were irradiated as
      subconfluent cultures using Cs-137 gamma rays at a dose rate of 1.75 Gy/min.
      Cultures were pretreated with Taxol (7.5 nM for 12 h, S.F. = 0.4) and then
      irradiated with graded doses followed by either immediate plating or holding for
      6 h either in the absence or presence of 7.5 nM Taxol prior to plating for colony
      forming ability. Experiments in which cells were irradiated and then exposed to
      7.5 nM Taxol for both 12 and 18 h were also performed. Parallel-flow cytometric
      analyses of cell-cycle distribution of the various treated populations were
      carried out. RESULTS: The results indicate that pretreatment with Taxol induced a
      G2 block which was maintained during 6 h postirradiation holding either in the
      presence or absence of Taxol. No modification of radiosensitivity in the low-dose
      region was seen for cells treated with Taxol, irradiated, and plated immediately,
      with the resulting survival being compatible with an additive effect. However,
      for Taxol-pretreated cells held for 6 h postirradiation, either in the absence or
      presence of Taxol, the resulting survival reproducibly demonstrated a marked less
      than additive effect. This was particularly prominent for cells held in the
      presence of Taxol. Subsequent experiments in which Taxol was added to cells
      immediately postirradiation again demonstrated a less than additive effect of the
      two modalities. CONCLUSION: The results of this study are consistent with a dual
      mechanism of action involving Taxol-induced radiation resistance, possibly as a
      consequence of postirradiation holding in G2, and radiation-induced Taxol
      resistance through an as-yet-undefined mechanism.

PMID- 9169825
TI  - Acceleration of hemopoietic recovery in dogs after extended-field partial-body
      irradiation by treatment with colony-stimulating factors: rhG-CSF and rhGM-CSF.
AB  - PURPOSE: The influence of treatment with the two colony-stimulating factors, rhG
      CSF and rhGM-CSF, on the hemopoietic recovery in aplastic bone marrow sites after
      extended-field irradiation was studied in a canine model. METHODS AND MATERIALS:
      The dogs received irradiation of the cranial part of their body with a single
      dose of 11.7 Gy, comprising approximately 72% of the total bone marrow mass.
      Anatomically this type of exposure corresponds to upper body irradiation (UBI) as
      employed under clinical conditions. Treatment with both the CSFs was employed for
      7 days by daily injections of 30 microg/kg, starting 24 hr after irradiation.
      RESULTS: Treatment with rhGM-CSF did not completely prevent the initial decrease
      of the granulocyte counts, but caused an accelerated, though incomplete, recovery
      in the period from day 5 to day 15. In contrast, treatment with rhG-CSF caused
      two phases of granulocytosis and an early recovery to normal levels at day 11
      after irradiation. Treatment with rhG-CSF, but not with rhGM-CSF, was associated
      with a strong supra-normal increase of progenitor cells in the blood within the
      first 8 days and an accelerated hemopoietic recovery in the irradiated sites
      particularly within the first 7 days after the exposure. CONCLUSIONS: These
      results indicate that under conditions of partial-body irradiation short term
      treatment with G-CSF is superior to GM-CSF in initiating the hemopoietic recovery
      on the basis of endogenous stem cell seeding.

PMID- 9169826
TI  - Reproducible rat model for comparing late rectal toxicity from different
      brachytherapy techniques.
AB  - PURPOSE: Newer brachytherapy techniques, such as pulse-simulated low dose rate
      (PDR) and high dose rate (HDR) offer clinical and technical advantages over the
      conventional continuous low dose rate (CLDR) irradiation. The impact of these
      techniques on late normal tissue toxicity has remained largely undefined, with
      mathematical modeling and limited clinical experience providing some guidelines.
      We sought to develop a reproducible rat model for quantifying and comparing late
      rectal toxicity from different brachytherapy techniques. METHODS AND MATERIALS:
      An intrarectal applicator has been designed and techniques have been developed to
      deliver clinically relevant doses of CLDR to allow comparison to PDR and HDR.
      Female Wistar rats are utilized. The endpoints assessed are rectal obstruction
      and a histological grading of late rectal injury. RESULTS: Analysis of 65 rats
      given either sham or single acute pulse irradiation has demonstrated the model to
      be reproducible and reliable in evaluating late rectal toxicity. CONCLUSIONS: The
      use of this rat model to compare late rectal injury from various doses, dose
      rates, and fractionation parameters utilized by CLDR, PDR, and HDR will provide
      another tool for safely implementing these techniques into the clinical setting.

PMID- 9169827
TI  - A volumetric study of measurements and calculations of lung density corrections
      for 6 and 18 MV photons.
AB  - PURPOSE: For treatment of lung cancer, dose heterogeneity corrections and
      subsequent prescription alteration remain controversial. Previous dosimetry
      studies based on slab geometry with a single beam geometry do not represent the
      clinical situation. A circumscribed tumor within lung poses a more complex
      problem. Energy choice also remains controversial. METHODS AND MATERIALS: An
      anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm
      diameters by 5.0 cm length) with muscle-equivalent cylinders. The phantom was
      scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV,
      CTV, PTV1 including tumor and regional nodes, PTV2 including tumor only) were
      designated slice-by-slice. Three-dimensional planning was performed with large
      fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2, for 6
      and 18 MV photons. Homogeneous, Ratio-Tissue-Air-Ratio (RTAR), and convolution
      adapted RTAR (CARTAR) calculation algorithms were tested. Film was placed between
      phantom slices at the "tumor" levels. The phantom was irradiated with monitor
      units corresponding to homogeneous calculations, based on a homogeneous
      prescription. Measured and calculated doses were compared by isodoses and dose
      volume histograms. Ionization chambers and TLDs were also used for some test
      cases. RESULTS: The measured minimum dose covering PTV2 was within 5% of the
      homogeneous prescription dose of 70 Gy for 6 MV photons, while a lower dose (89%
      of prescription dose) was measured for 18 MV. The algorithms overpredicted the
      minimum dose to PTV2 by 6-18%. If the monitor units had been reduced according to
      simplistic heterogeneous calculations, the small PTV2 would have only been
      covered by 58 Gy for 18 MV irradiation. Based on this, a clinician may opt to
      actually increase the prescribed dose, thereby offsetting decreased monitor
      units. None of the algorithms predicted the diffuse penumbra associated with 18
      MV photons in lung. CONCLUSION: Before adjusting dose prescriptions based on
      heterogeneity corrections, realistic phantom studies must be performed. The
      accuracy and effect of the corrections must then be assessed. The deficient
      coverage of PTV2 by the 18 MV beam compares unfavorably with the slight increase
      (5%) in hot spots associated with 6 MV. Our studies support strong caution before
      reducing dose prescriptions based on simple algorithms.

PMID- 9169828
TI  - Consequences of optimization in PDR brachytherapy--is a routine geometrical
      optimization recommendable?
AB  - PURPOSE: On the basis of clinical examples for interstitial volume implants and
      surface molds the benefit and disadvantage of optimization in pulsed dose rate
      (PDR) brachytherapy using a stepping source was investigated. Geometrically
      optimized PDR dose distributions were compared with nonoptimized ones as produced
      by Ir wires. METHODS AND MATERIALS: In 25 patients who were treated with a double
      plane interstitial breast implant with flexible catheters the first smoothly
      surrounding isodose, the reference volume and the uniformity and quality index
      derived from natural dose-volume histograms (Anderson) were considered. The
      effect of geometrical optimization on surface molds, which were used to irradiate
      chest wall relapses from breast cancer, was investigated by analyzing the
      reference surface, dose profiles, and depth-dose curves of a source arrangement
      covering an area of 10 x 10 cm2. RESULTS: Only in 3 of 25 patients the dose
      distribution of the volume implant was worsened by geometrical volume
      optimization regarding the homogeneity or the first smoothly surrounding isodose.
      Predominantly geometrical volume optimization reduced underdosage at the edges of
      the implants and improved the dose uniformity. The reference volume was
      increased. The geometrical distance optimization of surface mold dose
      distributions resulted in an enhancement of the reference surface and an
      improvement of the dose homogeneity on the skin surface. CONCLUSIONS: Geometrical
      optimization substantially changes the dose distribution. Only in a minority of
      cases the dose distributions of volume implants were worsened by geometrical
      volume optimization. Nevertheless, a close look at the results has to be
      recommended, especially if an overdosage in the lateral regions of the dose
      distribution and a dose falloff near the middle catheters is observed. The
      enhancement of the reference volume by geometrical volume optimization must be
      considered when choosing the active lengths. In surface mold treatment planning
      geometrical distance optimization is necessary to achieve homogeneous dose
      distributions for irradiation fields of different size and shape.

PMID- 9169829
TI  - Impact of differences in ultrasound and computed tomography volumes on treatment
      planning of permanent prostate implants.
AB  - PURPOSE: Both ultrasound (US) and computerized tomography (CT) images have been
      used in the planning of prostate interstitial therapy. Ultrasound images more
      clearly define the apex and capsule of the prostate, while CT images define seed
      positions for postimplant dosimetry. Proper registration of the US volume with
      the CT volume is critical to the assessment of dosimetry. We therefore compared
      US and CT prostate volumes to determine if differences were significant. METHODS
      AND MATERIALS: Ten consecutive patients entered in an interstitial implant
      program were studied by pretreatment US. In addition, pretreatment CT scans were
      obtained and three physicians independently outlined the dimensions of the
      prostate on these images. The patients subsequently underwent placement of
      radioactive 125I or 103Pd. Postimplant CT images were obtained the next day and
      the postimplant prostate volumes were outlined by the same three physicians.
      Seven of 10 patients underwent late CT scans 9-14 months postimplant for
      comparison of preimplant and immediate postimplant CT studies. RESULTS: There
      were differences between US and CT volumes. Although the physician-to-physician
      variation was significant, the trends were consistent, with US prostate volume
      typically smaller (47%) than the preimplant CT volume and markedly smaller (120%)
      than the postimplant CT volume. Prostate volumes derived from late CT images did
      not consistently return to preimplant levels. CONCLUSIONS: Significant
      differences in volume of the prostate structure were found between US and CT
      images. The data suggests that: (a) Implants planned on CT tend to overestimate
      the size of the prostate and may lead to unnecessary implantation of the
      urogenital diaphragm and penile urethra. (b) Registration of initial US and
      postimplant CT prostate volumes required for accurate dosimetry is difficult due
      to the increased volume of prostate secondary to trauma. (c) Further study to
      determine the optimal time for the postimplant CT is necessary.

PMID- 9169830
TI  - The use of tertiary collimation for spinal irradiation with extended SSD electron
      fields.
AB  - PURPOSE: The spine can be treated with an electron beam when its maximum
      posterior depth is within the therapeutic range of electrons. Electron fields
      treated at extended source-to-surface distances (SSDs), however, have larger
      penumbras and narrower therapeutic isodose widths relative to those at the
      standard SSD of 100 cm. We investigated the use of tertiary collimation close to
      the patient surface for these fields to sharpen the penumbra, minimizing dose to
      normal tissue and maximizing target coverage. METHODS AND MATERIALS: Using film
      dosimetry in a polystyrene phantom, we measured the dose distribution for
      electron fields at extended SSD under varying collimation conditions. Beam
      penumbra and therapeutic width as a function of depth, SSD, applicator insert
      size, and tertiary collimator opening were determined. We also measured the dose
      distributions in the junction region for various gaps between x-ray fields and an
      electron field as used for craniospinal irradiation. RESULTS: Measurements show
      that tertiary collimation close to the skin surface reduces penumbra width
      (lateral distance between the 90 and 20% isodose lines) by 56% and increases
      therapeutic isodose width (lateral width of the 90% isodose curve) by 25% at a
      depth of dmax relative to standard collimation. These numbers change to 23 and
      13%, respectively, at an average depth of the spine. When lateral brain and
      posterior spine fields are used to irradiate the entire craniospinal axis,
      tertiary collimation aids in reducing the volume of the hot spot in the junction
      region by as much as 10% without compromising target coverage. CONCLUSIONS:
      Tertiary collimation for extended SSD electron fields is preferable to standard
      collimation in order to minimize dose to normal tissue and increase target
      coverage. This technique can be applied to both spinal and craniospinal
      irradiation. Support structures for the tertiary blocking are needed because the
      weight of the lead is usually too great for placement on the skin.

PMID- 9169831
TI  - Dynamics of pear-shaped dimensions and volume of intracavitary brachytherapy in
      cancer of the cervix: a desirable pear shape in the era of three-dimensional
      treatment planning.
AB  - PURPOSE: To evaluate the dynamics of pear-shaped dimensions and volume of the
      intracavitary brachytherapy, and to define a desirable pear-shape in the era of
      three-dimensional (3D) treatment planning. METHODS AND MATERIALS: Since Point A
      has been used for the dose specification, the pear shape defined the surface
      enclosed by Point A. This study utilized a new method of evaluating pear-shaped
      dimensions and its configuration. The pear shape was artificially divided into
      tandem and colpostat portions for evaluation of its changes. Width, height, and
      thickness at the tandem portion (Wt, Ht, and Tt) and at the colpostat portion
      (Wc, Hc, and Tc) were defined, respectively, on the frontal and sagittal plane.
      To evaluate the dynamics of the pear-shape configuration, 12 variations of
      applicator geometry and source loading were applied to generate the pear-shape
      isodose line and dose-volume histogram. RESULTS: When the source strengths in the
      colpostats were reduced for optimization with the same dose to Point A dose, Wc,
      Hc, and Tc were decreased, whereas Wt, Ht, and Tt were increased without a change
      in the overall pear-shaped volume. When the separation of the colpostats was
      increased without a change in the source strength, Wc was increased, whereas Hc
      and Tc were reduced without a change in Wt, Ht, Tt and overall pear-shape volume.
      When the separation of colpostats and distal tandem source were increased, these
      changes at the colpostat portion were magnified. However, when both colpostat
      separation and its source strength were increased proportionally, Wc, Hc, and Tc
      were increased proportionally as well as its volume. CONCLUSION: The dose
      specification at Point A is less meaningful without a desirable pear shape
      encompassing the tumor around the cervix. In the era of 3D treatment planning,
      understanding the dynamics of the pear shape should improve the individualized
      dosimetry according to tumor size and location. The relationships between a
      desirable pear shape and its tumor coverage should establish a more reliable dose
      specification for cancer of the cervix.

PMID- 9169832
TI  - Magnetically-enhanced radionuclide therapy (MERiT): in vitro evaluation.
AB  - PURPOSE: Radionuclide therapy is a promising method for delivering radiation dose
      selectively to tumors. In situations where electron -emitters are used and the
      tumor is small relative to the maximum range of therapeutic electrons, these
      particles exit the tumor before delivering the maximum amounts of radiation dose.
      In this study, the method of magnetically constraining electrons to small tumors,
      known as magnetically -enhanced radionuclide therapy (MERiT), is explored using
      in vitro experiments. METHODS AND MATERIALS: The potential utility of MERiT was
      investigated by first measuring the reduction of number of electrons exiting a
      small sphere containing 90Y embedded in a block of plastic scintillator.
      Measurements of total energy deposited in the plastic scintillator made inside
      and outside a 7 Tesla magnetic field were compared. Furthermore, an experiment
      utilizing lymphoma cells of human origin was performed. Groups of cells were
      added to wells containing 90Y-labeled bovine serum albumin (and control groups
      containing no radioactivity) were placed either inside a 7 Tesla magnet or at a
      position where the magnetic field was minimal (essentially zero) for 18 hr.
      RESULTS: The presence of a 7 Tesla magnetic field reduced the amount of energy
      deposited in the scintillator by 16.63 +/- 1.05%. This demonstrates that the
      magnetic field constrains a large fraction of the emissions to the sphere and
      implies that normal tissues adjacent to radiotracer-avid tumors can be protected
      from radiation dose. Results from the cell culture experiment showed that the
      presence of a 7 Tesla magnetic field significantly (p < 0.005) reduced the number
      of viable cells remaining after treatment with non-specific 90Y-labeled bovine
      serum albumin by 11.7% compared to the appropriate control group (90Y treated,
      not exposed to magnetic field). CONCLUSIONS: These initial physical and
      biological studies indicate that magnetically-enhanced radionuclide therapy can
      be effective in increasing radiation absorbed dose to small tumors, consequently
      reducing radiation dose to surrounding normal structures.

PMID- 9169833
TI  - The hardwiring of development: organization and function of genomic regulatory
      systems.
AB  - The gene regulatory apparatus that directs development is encoded in the DNA, in
      the form of organized arrays of transcription factor target sites. Genes are
      regulated by interactions with multiple transcription factors and the target
      sites for the transcription factors required for the control of each gene
      constitute its cis-regulatory system. These systems are remarkably complex. Their
      hardwired internal organization enables them to behave as genomic information
      processing systems. Developmental gene regulatory networks consist of the cis
      regulatory systems of all the relevant genes and the regulatory linkages amongst
      them. Though there is yet little explicit information, some general properties of
      genomic regulatory networks have become apparent. The key to understanding how
      genomic regulatory networks are organized, and how they work, lies in
      experimental analysis of cis-regulatory systems at all levels of the regulatory
      network.

PMID- 9169834
TI  - Association of Engrailed homeoproteins with vesicles presenting caveolae-like
      properties.
AB  - We report here that the homeoproteins Engrailed-1 and Engrailed-2 are present in
      specific non-nuclear subcellular compartments. Using electron microscopy, we
      observed that chick-Engrailed-2 expressed in COS-7 cells associates with membrane
      fractions that are characterized as caveolae. This characterization is based on
      morphological, biochemical and immunological criteria such as, in particular, the
      absence of clathrin coat and the presence of caveolin and cholera toxin-binding
      sites. These data are fully confirmed by subcellular fractionation experiments,
      which demonstrate that transfected chick-Engrailed-2 is present in low density
      membrane fractions that are resistant to Triton X-100, enriched in caveolin and
      solubilized by the addition of a cholesterol-binding detergent, a set of
      properties highly characteristic of caveolae. The association of Engrailed-2 with
      specific membrane fractions observed after transfection in COS-7 cells is also
      observed for endogenous Engrailed-1 and Engrailed-2 expressed at late embryonic
      stages in the cerebellum and posterior mesencephalon of the rodent. Indeed, the
      two proteins are present in membrane fractions that bear all the characteristics
      of microdomains or caveolae-like domains, i.e. Triton X-100 resistance, saponin
      solubilization, low density on sucrose gradients, enrichment in glycosphingolipid
      GM1, absence of transmembrane Neural Cell Adhesion Molecule, presence of the
      glypiated (GPI-anchored) glycoprotein F3/F11 and of the acylated growth
      associated protein GAP-43. Finally we demonstrate that part of the membrane
      associated Engrailed, either expressed in COS-7 cells or endogenously present in
      neural tissues, is not accessible to proteolytic enzymes unless the membranes
      have been permeabilized with detergent. This study suggests that, in addition to
      their well-known presence in the nucleus, Engrailed proteins are also associated
      with caveolae-like vesicles that are primarily transported anterogradely into the
      axon, and that they can get access to a compartment compatible with secretion.

PMID- 9169835
TI  - Coordination of early neural tube development by BDNF/trkB.
AB  - Neurotrophins signal through members of the trk family of tyrosine kinase
      receptors and are known to regulate several neuronal properties. Although
      initially characterized by their ability to prevent naturally occurring cell
      death of subsets of neurons during development, neurotrophins can also regulate
      the proliferation and differentiation of precursor cells. Here we report a novel
      involvement of neurotrophins in early development of the neural tube. We
      demonstrate that a functional trkB receptor is expressed by motor neuron
      progenitors in the ventral neural tube and that treatment of ventral neural tube
      explants with the trkB ligand Brain-Derived Neurotrophic Factor (BDNF) leads to a
      significant increase in the number of motor neurons. The only BDNF expression
      detectable at this stage is by a subset of ventrally projecting interneurons in
      the dorsal neural tube; ablating this region in vivo leads to a reduction of
      motor neuron numbers. This loss can be prevented by simultaneous treatment with
      BDNF. We propose that BDNF produced by dorsal interneurons stimulates
      proliferation and/or differentiation of motor neuron progenitors after
      anterograde axonal transport and release in proximity to the trkB-expressing
      motor neuron precursors, thereby coordinating development between dorsal and
      ventral regions of the neural tube.

PMID- 9169836
TI  - Differential expression of mammalian Numb, Numblike and Notch1 suggests distinct
      roles during mouse cortical neurogenesis.
AB  - During Drosophila neurogenesis, asymmetric cell divisions are achieved by
      differential segregation of Numb (d-Numb) into one of the daughter cells to cause
      a bias in the Notch mediated cell-cell interaction. We have isolated a second
      mammalian gene with significant sequence similarity to d-numb, mouse numblike.
      When expressed in dividing neural precursors in Drosophila, Numblike is
      symmetrically distributed in the cytoplasm, unlike endogenous d-Numb or expressed
      mouse Numb (m-Numb), both of which are asymmetrically localized to one half of
      the cell membrane. In d-numb loss-of-function mutant embryos, expression of
      Numblike allows both daughter cells of a neural precursor to adopt the fate of
      the cell that normally inherits d-Numb. In mice, numblike mRNA is preferentially
      expressed in adult and embryonic nervous system. In the developing neocortex,
      Numblike is expressed in postmitotic neurons in the cortical plate, but not in
      progenitors within the ventricular zone where m-Numb and Notch1 are expressed. We
      have also found that, in dividing cortical progenitors, Notch1 is distributed
      around the entire membrane, unlike m-Numb which is asymmetrically localized to
      the apical membrane. We propose that an interplay between cell-intrinsic
      mechanisms (executed by m-numb and numblike) and cell-extrinsic mechanisms
      (mediated by Notch1) may be involved in both progenitor cell proliferation and
      neuronal differentiation during mammalian cortical neurogenesis.

PMID- 9169837
TI  - Skeletal morphogenesis in the sea urchin embryo: regulation of primary mesenchyme
      gene expression and skeletal rod growth by ectoderm-derived cues.
AB  - The skeleton of the sea urchin embryo is synthesized by the primary mesenchyme
      cells (PMCs). Previous studies have shown that local interactions between PMCs
      and the neighboring ectoderm regulate several aspects of skeletal morphogenesis,
      including PMC distribution in the blastocoel, the size of the skeleton and its
      branching pattern. In the present study, we have further examined the regulation
      of skeletogenesis by the ectoderm. We generated a 'rate map' of skeletal growth,
      which revealed stereotypical changes in the rates at which specific skeletal
      elements elongate during development. We showed that three transcripts encoding
      PMC-specific gene products known to be involved in the synthesis of the skeleton
      exhibited dynamic, spatially regulated patterns of expression within the PMC
      syncytium. All three gene products showed high levels of expression at sites of
      skeletal rod growth, although the specific patterns varied among the genes. We
      present direct evidence, based upon cell transplantation experiments, that the
      expression of one of these genes, SM30, is responsive to local, ectoderm-derived
      cues. Based upon our studies, we suggest that short-range signals from different
      ectodermal territories may regulate the expression of PMC-specific gene products
      that are rate-limiting in skeletal biosynthesis, thereby locally influencing
      skeletal rod growth.

PMID- 9169838
TI  - Cell fate in the chick limb bud and relationship to gene expression.
AB  - We have produced detailed fate maps for mesenchyme and apical ridge of a stage 20
      chick wing bud. The fate maps of the mesenchyme show that most of the wing arises
      from the posterior half of the bud. Subapical mesenchyme gives rise to digits.
      Cell populations beneath the ridge in the mid apical region fan out into the
      anterior tip of the handplate, while posterior cell populations extend right
      along the posterior margin. Subapical mesenchyme of the leg bud behaves
      similarly. The absence of anterior bending of posterior cell populations has
      implications when considering models of vertebrate limb evolution. The fatemaps
      of the apical ridge show that there is also a marked anterior expansion and cells
      that were in anterior apical ridge later become incorporated into non-ridge
      ectoderm along the margin of the bud. Mesenchyme and apical ridge do not expand
      in concert--the apical ridge extends more anteriorly. We used the fatemaps to
      investigate the relationship between cell lineage and elaboration of Hoxd-13 and
      Fgf-4 domains. Hoxd-13 and Fgf-4 are initially expressed posteriorly until about
      the mid-point of the early wing bud in mesenchyme and apical ridge respectively.
      Later in development, the genes come to be expressed throughout most of the
      handplate and apical ridge respectively. We found that at the proximal edge of
      the Hoxd-13 domain, cell populations stopped expressing the gene as development
      proceeded and found no evidence that the changes in extent of the domains were
      due to initiation of gene expression in anterior cells. Instead the changes in
      extent of expression fit with the fate maps and can be attributed to expansion
      and fanning out of cell populations initially expressing the genes.

PMID- 9169839
TI  - Notch signalling regulates veinlet expression and establishes boundaries between
      veins and interveins in the Drosophila wing.
AB  - The veins in the Drosophila wing have a characteristic width, which is regulated
      by the activity of the Notch pathway. The expression of the Notch-ligand Delta is
      restricted to the developing veins, and coincides with places where Notch
      transcription is lower. We find that this asymmetrical distribution of ligand and
      receptor leads to activation of Notch on both sides of each vein within a
      territory of Delta-expressing cells, and to the establishment of boundary cells
      that separate the vein from adjacent interveins. In these cells, the expression
      of the Enhancer of split gene m beta is activated and the transcription of the
      vein-promoting gene veinlet is repressed, thus restricting vein differentiation.
      We propose that the establishment of vein thickness utilises a combination of
      mechanisms that include: (1) independent regulation of Notch and Delta expression
      in intervein and vein territories, (2) Notch activation by Delta in cells where
      Notch and Delta expression overlaps, (3) positive feedback on Notch transcription
      in cells where Notch has been activated and (4) repression of veinlet
      transcription by E(spl)m beta and maintenance of Delta expression by
      veinlet/torpedo activity.

PMID- 9169840
TI  - Identification of a lineage of multipotent hematopoietic progenitors.
AB  - All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are
      divided among three subpopulations of Thy-1.1(lo) Sca-1+ Lin(-/lo) c-kit+ cells:
      long-term reconstituting Mac-1- CD4- c-kit+ cells and transiently reconstituting
      Mac-1(lo) CD4- or Mac-1(lo) CD4(lo) cells. This study shows that the same
      populations, with similar functional activities, exist in mice whose
      hematopoietic systems were reconstituted by hematopoietic stem cells after lethal
      irradiation. We demonstrate that these populations form a lineage of multipotent
      progenitors from long-term self-renewing stem cells to the most mature
      multipotent progenitor population. In reconstituted mice, Mac-1- CD4- c-kit+
      cells gave rise to Mac-1(lo) CD4- cells, which gave rise to Mac-1(lo) CD4(lo)
      cells. Mac-1- CD4- c-kit+ cells had long-term self-renewal potential, with each
      cell being capable of giving rise to more than 10(4) functionally similar Mac-1-
      CD4- c-kit+ cells. At least half of Mac-1(lo) CD4- cells had transient self
      renewal potential, detected in the spleen 7 days after reconstitution. Mac-1(lo)
      CD4(lo) cells did not have detectable self-renewal potential. The identification
      of a lineage of multipotent progenitors provides an important tool for
      identifying genes that regulate self-renewal and lineage commitment.

PMID- 9169841
TI  - Competition and cooperation among receptor tyrosine phosphatases control
      motoneuron growth cone guidance in Drosophila.
AB  - The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved
      in motor axon guidance in the Drosophila embryo. Here we analyze the requirements
      for these three phosphatases in growth cone guidance decisions along the ISN and
      SNb motor pathways. Any one of the three suffices for the progression of ISN
      pioneer growth cones beyond their first intermediate target in the dorsal muscle
      field. DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate
      target, and DLAR is uniquely required for formation of a normal terminal arbor. A
      different pattern of partial redundancy among the three phosphatases is observed
      for the SNb pathway. Any one of the three suffices to allow SNb axons to leave
      the common ISN pathway at the exit junction. When DLAR is not expressed, however,
      SNb axons sometimes bypass their ventrolateral muscle targets after leaving the
      common pathway, instead growing out as a separate bundle adjacent to the ISN.
      This abnormal guidance decision can be completely suppressed by also removing
      DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that
      favors the bypass axon trajectory. Our results show that the relationships among
      the tyrosine phosphatases are complex and dependent on cellular context. At
      growth cone choice points along one nerve, two phosphatases cooperate, while
      along another nerve these same phosphatases can act in opposition to one another.

PMID- 9169842
TI  - Regulation of the neural crest cell fate by N-myc: promotion of ventral migration
      and neuronal differentiation.
AB  - During neural crest development in avian embryos, transcription factor N-myc is
      initially expressed in the entire cell population. The expression is then turned
      off in the period following colonization in ganglion and nerve cord areas except
      for the cells undergoing neuronal differentiation. This was also recapitulated in
      the culture of Japanese quail neural crest, and the cells expressing N-myc
      eventually coincided with those expressing neurofilaments. These findings
      suggested that N-myc is involved in regulation of neuronal differentiation in the
      neural crest cell population. In fact, transient overexpression of N-myc in the
      neural crest culture by transfection resulted in a remarkable promotion of
      neuronal differentiation. An experimental procedure was developed to examine the
      effect of exogenous N-myc expression in the neural crest cells in embryos. Neural
      crest cell clusters still attached to the neural tube were excised from Japanese
      quail embryos, transfected and grafted into chicken host embryos. Using this
      chimera technique, we were able to analyze the consequence of transient high N
      myc during the early phase of neural crest migration. Two effects were
      demonstrated in the embryos: first, high N-myc expression provoked massive
      ventral migration of the neural crest population and, second, those cells that
      migrated to the ganglion-forming areas underwent neuronal differentiation with
      the cell type determined by the nature of the ganglion. Thus, N-myc is involved
      in regulation of the neural crest fate in two different aspects: ventral
      migration and neuronal differentiation.

PMID- 9169843
TI  - Transcription factor mTEAD-2 is selectively expressed at the beginning of zygotic
      gene expression in the mouse.
AB  - mTEF-1 is the prototype of a family of mouse transcription factors that share the
      same TEA DNA binding domain (mTEAD genes) and are widely expressed in adult
      tissues. At least one member of this family is expressed at the beginning of
      mouse development, because mTEAD transcription factor activity was not detected
      in oocytes, but first appeared at the 2-cell stage in development, concomitant
      with the onset of zygotic gene expression. Since embryos survive until day 11 in
      the absence of mTEAD-1 (TEF-1), another family member likely accounts for this
      activity. Screening an EC cell cDNA library yielded mTEAD-1, 2 and 3 genes. RT
      PCR detected RNA from all three of these genes in oocytes, but upon
      fertilization, mTEAD-1 and 3 mRNAs disappeared. mTEAD-2 mRNA, initially present
      at approx. 5,000 copies per egg, decreased to approx. 2,000 copies in 2-cell
      embryos before accumulating to approx. 100,000 copies in blastocysts, consistent
      with degradation of maternal mTEAD mRNAs followed by selective transcription of
      mTEAD-2 from the zygotic genome. In situ hybridization did not detect mTEAD RNA
      in oocytes, and only mTEAD-2 was detected in day-7 embryos. Northern analysis
      detected all three RNAs at varying levels in day-9 embryos and in various adult
      tissues. A fourth mTEAD gene, recently cloned from a myotube cDNA library, was
      not detected by RT-PCR in either oocytes or preimplantation embryos. Together,
      these results reveal that mTEAD-2 is selectively expressed for the first 7 days
      of embryonic development, and is therefore most likely responsible for the mTEAD
      transcription factor activity that appears upon zygotic gene activation.

PMID- 9169844
TI  - Mesodermal subdivision along the mediolateral axis in chicken controlled by
      different concentrations of BMP-4.
AB  - Molecular mechanisms by which the mesoderm is subdivided along the mediolateral
      axis in early chicken embryos have been studied. When the presomitic mesoderm
      (medial mesoderm) was transplanted into the lateral plate, the graft was
      transformed into lateral plate tissue, indicating that the primitive somite was
      not fully committed and that the lateral plate has a cue for mesodermal
      lateralization. Since the lateral plate expresses a high level of BMP-4 mRNA, a
      member of the TGF-beta family, we hypothesized that it is the molecule
      responsible for the lateralization of the somite. To test this, we transplanted
      COS cells producing BMP-4 into the presomitic region. Those cells locally
      prevented the presomitic cells from differentiating into somites, converting them
      instead into lateral plate mesoderm, which was revealed by expression of
      cytokeratin mRNA, a marker for the lateral plate. The effect was dependent on the
      level of effective BMP-4: with a high level of BMP-4, the somite was transformed
      completely to lateral plate; with a low level, the somite formed but was occupied
      by the lateral somitic component expressing cSim 1, a marker for the lateral
      somite. These results suggest that different thresholds of effective BMP-4
      determine distinct subtypes of the mesoderm as a lateralizer during early
      development.

PMID- 9169845
TI  - Pax-6 functions in boundary formation and axon guidance in the embryonic mouse
      forebrain.
AB  - The Pax-6 gene encodes a transcription factor that is expressed in regionally
      restricted patterns in the developing brain and eye. Here we describe Pax-6
      expression in the early forebrain (prosencephalon) on embryonic day 9.5 (E9.5) to
      E10.5 using both whole-mount in situ hybridization and antibody labeling. We find
      close correlations between Pax-6+ domains and initial neural patterning, and
      identify corresponding defects in embryos homozygous for the Pax-6 allele, Small
      eye (Sey). Pax-6 expression defines the prosencephalon-mesencephalon boundary,
      and mutant embryos lack this morphological boundary. Markers of the caudal
      prosencephalon are lost (Pax-6, Lim-1, Gsh-1) and a marker for mesencephalon is
      expanded rostrally into the prosencephalon (Dbx). We conclude that the caudal
      prosencephalon (prosomere 1) is at least partially transformed to a mesencephalic
      fate. This transformation results in a specific deficit of posterior commissure
      axons. Sey/Sey embryos also exhibit an axon pathfinding defect specific to the
      first longitudinal tract in the prosencephalon (tpoc, tract of the postoptic
      commissure). In wild type, tpoc axons fan out upon coming in contact with a
      superficial patch of Pax-6+ neuron cell bodies. In the mutant, the tpoc axons
      have normal initial projections, but make dramatic errors where they contact the
      neuron cell bodies, and fail to pioneer this first tract. Thus Pax-6 is required
      for local navigational information used by axons passing through its domain of
      expression. We conclude that Pax-6 plays multiple roles in forebrain patterning,
      including boundary formation, regional patterning, neuron specification and axon
      guidance.

PMID- 9169846
TI  - Reassessing embryogenesis in the Ctenophora: the inductive role of e1 micromeres
      in organizing ctene row formation in the 'mosaic' embryo, Mnemiopsis leidyi.
AB  - Ctenophores are a phylum of diploblastic marine animals displaying biradial
      symmetry organized along an oral-aboral axis. One of the apomorphic sets of adult
      structures in ctenophores are the eight external comb rows, which run along the
      oral-aboral axis. Comb rows consist of serial arrays of individual comb plates of
      cilia, which beat in a coordinated fashion for locomotory behavior. Classical
      cell lineage experiments using chalk particles indicated that comb rows are
      derived exclusively from the four e1 micromeres at the 16-cell stage. This
      conclusion was also supported by the fact that no ctene rows (or their underlying
      endodermal canals) form when all four e1 micromeres were deleted. We have used
      intracellular diI cell lineage tracing to determine that, in addition to e1
      micromeres, the four m1 micromeres also make significant contributions to the
      ctene rows. Thus, e1 micromere derivatives not only generate comb plates but are
      required for ctene row formation by m1 derivatives. These results demonstrate
      that inductive interactions are an important component of early development in
      ctenophores and indicate that e1 micromeres influence the development of adjacent
      cell lineages (both m1 and endodermal lineages) during ctenophore embryogenesis.
      In addition, intracellular labeling has revealed that there are subtle variations
      in the composition of clones derived from identified embryonic blastomeres.
      Together these findings reveal a picture of ctenophore embryogenesis, which is in
      marked contrast to the former rigid 'mosaic' reputation of ctenophore
      development, and invite speculation as to the role of the cleavage program in
      embryonic patterning in the lower Metazoa.

PMID- 9169847
TI  - Switching the in vivo specificity of a minimal Hox-responsive element.
AB  - The homeodomain proteins encoded by the Hox complex genes do not bind DNA with
      high specificity. In vitro, Hox specificity can be increased by binding to DNA
      cooperatively with the homeodomain protein extradenticle or its vertebrate
      homologs, the pbx proteins (together, the PBC family). Here we show that a two
      basepair change in a Hox-PBC binding site switches the Hox-dependent expression
      pattern generated in vivo, from labial to Deformed. The change in vivo correlates
      with an altered Hox binding specificity in vitro. Further, we identify similar
      Deformed-PBC binding sites in the Deformed and Hoxb-4 genes and show that they
      generate Deformed or Hoxb-4 expression patterns in Drosophila and mouse embryos,
      respectively. These results suggest a model in which Hox-PBC binding sites play
      an instructive role in Hox specificity by promoting the formation of different
      Hox-PBC heterodimers in vivo. Thus, the choice of Hox partner, and therefore Hox
      target genes, depends on subtle differences between Hox-PBC binding sites.

PMID- 9169848
TI  - Transcriptional regulation of Notch and Delta: requirement for neuroblast
      segregation in Drosophila.
AB  - Segregation of a single neural precursor from each proneural cluster in
      Drosophila relies on Notch-mediated lateral signalling. Studies concerning the
      spacing of precursors for the microchaetes of the peripheral nervous system
      suggested the existence of a regulatory loop between Notch and its ligand Delta
      within each cell that is under transcriptional control. Activation of Notch leads
      to repression of the achaete-scute genes which themselves regulate transcription
      of Delta, perhaps directly. Here we have tested a requirement for transcriptional
      regulation of Notch and/or Delta during neuroblast segregation in embryos, by
      providing Notch and Delta ubiquitously at uniform levels. Neuroblast segregation
      occurs normally under conditions of uniform Notch expression. Under conditions of
      uniform Delta expression, a single neuroblast segregates from each proneural
      group in 80% of the cases, more than one in the remaining 20%. Thus
      transcriptional regulation of Delta is largely dispensable. We discuss the
      possibility that segregation of single precursors in the central nervous system
      may rely on a heterogeneous distribution of neural potential between different
      cells of the proneural group. Notch signalling would enable all cells to mutually
      repress each other and only a cell with an elevated neural potential could
      overcome this repression.

PMID- 9169849
TI  - Tight junction assembly during mouse blastocyst formation is regulated by late
      expression of ZO-1 alpha+ isoform.
AB  - The mouse preimplantation embryo has been used to investigate the de novo
      synthesis of tight junctions during trophectoderm epithelial differentiation. We
      have shown previously that individual components of the tight junction assemble
      in a temporal sequence, with membrane assembly of the cytoplasmic plaque protein
      ZO-1 occurring 12 hours before that of cingulin. Subsequently, two alternatively
      spliced isoforms of ZO-1 (alpha+ and alpha-), differing in the presence or
      absence of an 80 residue alpha domain were reported. Here, the temporal and
      spatial expression of these ZO-1 isoforms has been investigated at different
      stages of preimplantation development. ZO-1alpha- mRNA was present in oocytes and
      all preimplantation stages, whilst ZO-1alpha+ transcripts were first detected in
      embryos at the morula stage, close to the time of blastocoele formation. mRNAs
      for both isoforms were detected in trophectoderm and ICM cells.
      Immunoprecipitation of 35S-labelled embryos also showed synthesis of ZO-1alpha-
      throughout cleavage, whereas synthesis of ZO-1alpha+ was only apparent from the
      blastocyst stage. In addition, 33P-labelling showed both isoforms to be
      phosphorylated at the early blastocyst stage. The pattern and timing of membrane
      assembly of the two isoforms was also distinct. ZO-1alpha- was initially seen as
      punctate sites at the cell-cell contacts of compact 8-cell embryos. These sites
      then coalesced laterally along the membrane until they completely surrounded each
      cell with a zonular belt by the late morula stage. ZO-1alpha+ however, was first
      seen as perinuclear foci in late morulae before assembling at the tight junction.
      Membrane assembly of ZO-1alpha+ first occurred during the 32-cell stage and was
      zonular just prior to the early blastocyst stage. Immunostaining indicative of
      both isoforms was restricted to the trophectoderm lineage. Membrane assembly of
      ZO-1alpha+ and blastocoele formation were sensitive to brefeldin A, an inhibitor
      of intracellular trafficking beyond the Golgi complex. In addition, the tight
      junction transmembrane protein occludin co-localised with ZO-1alpha+ at the
      perinuclear sites in late morulae and at the newly assembled cell junctions.
      These results provide direct evidence from a native epithelium that ZO-1 isoforms
      perform distinct roles in tight junction assembly. Moreover, the late expression
      of ZO-1alpha+ and its apparent intracellular interaction with occludin may act as
      a final rate-limiting step in the synthesis of the tight junction, thereby
      regulating the time of junction sealing and blastocoele formation in the early
      embryo.

PMID- 9169850
TI  - Flk-1 expression defines a population of early embryonic hematopoietic
      precursors.
AB  - We have investigated the expression pattern of the Flk-1 receptor tyrosine kinase
      in mouse embryonic and fetal hematopoietic tissues as well as on hematopoietic
      precursor cells derived from these tissues. RNA analysis indicated that flk-1 was
      expressed in the yolk sac at day 10 of gestation, in the whole embryo at day 10
      and 12 of gestation, in the liver throughout fetal life and in embryoid bodies
      (EBs) generated from ES cells differentiated in culture. Flk-1 message was also
      detected in erythroid and macrophage colonies generated from precursors of yolk
      sac, fetal liver, adult marrow and EB origin. Using an antibody directed against
      the extracellular portion of the molecule we have found that up to 50% of cells
      from EBs differentiated for 4 days express Flk-1. Following the development of
      this early Flk-1+ population the number of receptor-positive cells declines
      progressively to represent less than 5% of the EBs by day 12 of differentiation.
      Kinetic analysis revealed that the establishment of the EB Flk-1+ population
      precedes the development of cells which express CD34, Ly6A (Sca-1) and AA4.1.
      Cell sorting experiments demonstrated that all day-4 EB-derived hematopoietic
      precursors are Flk-1+ whereas greater than 95% of those found within the day-12
      EBs are Flk-1-, suggesting that the precursor population which expresses this
      receptor represents an early but transient wave of hematopoietic development.
      Analysis of yolk sac and whole embryos at day 8.5 of gestation revealed a small
      but distinct Flk-1+ population that contained hematopoietic precursors. Day-12.5
      fetal liver contained few Flk-1+ cells that showed little hematopoietic
      potential. Together these findings indicate that Flk-1 is expressed on an early
      population of hematopoietic precursors that may represent the onset of embryonic
      hematopoiesis.

PMID- 9169852
TI  - The C. elegans gene pag-3 is homologous to the zinc finger proto-oncogene gfi-1.
AB  - Mutations in the Caenorhabditis elegans gene pag-3 result in misexpression of
      touch receptor-specific genes in the BDU interneurons and in motility defects. We
      cloned pag-3 and found that the gene encodes a C2H2-type zinc finger protein
      related to the mammalian GFI-1 protein. Sequencing of the three pag-3 alleles
      showed that two apparent null alleles encode a nonsense mutation before the zinc
      fingers and a missense mutation in the fourth zinc finger that changes a
      coordinating histidine to a tyrosine. The third allele contains a nonsense
      mutation in the N-terminal region but is not a null allele. Northern analysis
      showed that a single pag-3 transcript of about 1.6 kb is present in embryos and
      L1, L2 and L3 larvae. pag-3 message levels were about twofold higher in pag-3
      mutants than in wild-type animals, which suggested that pag-3 may negatively
      regulate its own expression. pag-3lacZ fusion genes were expressed in the BDU
      interneurons, the touch neurons, 11 VA and 11 VB ventral cord motor neurons, two
      AVF interneurons and in unidentified neurons of the retrovesicular ganglion. The
      BDU neurons and the ALM touch neurons are lineal sister cells in the AB.a lineage
      and the VA and VB motor neurons are lineal sister cells in the AB.p lineage. The
      VA motor neurons are required for backward movement and the VB motor neurons are
      required for forward movement. Mosaic analysis showed that the wild-type pag-3
      gene is required in the AB.p lineage for coordinated movement and in the AB.a
      lineage to suppress touch neuron gene expression in the BDU neurons. Because pag
      3 is expressed in both the BDU neurons and in the touch neurons, another
      protein(s) not expressed in the touch neurons may interact with pag-3 to repress
      touch neuron gene expression in the BDU neurons. Alternatively, another protein
      in the touch receptor cells may inactivate PAG-3 and allow expression of the
      touch receptor program. These results show that pag-3 is a temporally regulated
      gene that is expressed early in development and functions in multiple types of
      neurons. They also strongly suggest that the PAG3 protein is a DNA-binding
      protein with properties similar to the mammalian proto-oncogene product GFI-1.

PMID- 9169851
TI  - A leucine-rich repeat containing receptor-like kinase marks somatic plant cells
      competent to form embryos.
AB  - The first somatic single cells of carrot hypocotyl explants having the competence
      to form embryos in the presence of 2,4-dichlorophenoxyacetic acid (2,4-D) were
      identified using semi-automatic cell tracking. These competent cells are present
      as a small subpopulation of enlarged and vacuolated cells derived from cytoplasm
      rich and rapidly proliferating non-embryogenic cells that originate from the
      provascular elements of the hypocotyl. A search for marker genes to monitor the
      transition of somatic into competent and embryogenic cells in established
      suspension cell cultures resulted in the identification of a gene transiently
      expressed in a small subpopulation of the same enlarged single cells that are
      formed during the initiation of the embryogenic cultures from hypocotyl explants.
      The predicted amino acid sequence and in vitro kinase assays show that this gene
      encodes a leucine-rich repeat containing receptor-like kinase protein, designated
      Somatic Embryogenesis Receptor-like Kinase (SERK). Somatic embryos formed from
      cells expressing a SERK promoter-luciferase reporter gene. During somatic
      embryogenesis, SERK expression ceased after the globular stage. In plants, SERK
      mRNA could only be detected transiently in the zygotic embryo up to the early
      globular stage but not in unpollinated flowers nor in any other plant tissue.
      These results suggest that somatic cells competent to form embryos and early
      globular somatic embryos share a highly specific signal transduction chain with
      the zygotic embryo from shortly after fertilization to the early globular embryo.

PMID- 9169853
TI  - Expression of Pax-3 is initiated in the early neural plate by posteriorizing
      signals produced by the organizer and by posterior non-axial mesoderm.
AB  - Pax-3 is a paired-type homeobox gene that is specifically expressed in the dorsal
      and posterior neural tube. We have investigated inductive interactions that
      initiate Pax-3 transcript expression in the early neural plate. We present
      several lines of evidence that support a model where Pax-3 expression is
      initiated by signals that posteriorize the neuraxis, and then secondarily
      restricted dorsally in response to dorsal-ventral patterning signals. First, in
      chick and Xenopus gastrulae the onset of Pax-3 expression occurs in regions fated
      to become posterior CNS. Second, Hensen's node and posterior non-axial mesoderm
      which underlies the neural plate induce Pax-3 expression when combined with
      presumptive anterior neural plate explants. In contrast, presumptive anterior
      neural plate explants are not competent to express Pax-3 in response to
      dorsalizing signals from epidermal-ectoderm. Third, in a heterospecies explant
      recombinant assay with Xenopus animal caps (ectoderm) as a responding tissue,
      late, but not early, Hensen's node induces Pax-3 expression. Chick posterior non
      axial mesoderm also induces Pax-3, provided that the animal caps are neuralized
      by treatment with noggin. Finally we show that the putative posteriorizing
      factors, retinoic acid and bFGF, induce Pax-3 in neuralized animal caps. However,
      blocking experiments with a dominant-inhibitory FGF receptor and a dominant
      inhibitory retinoic acid receptor suggest that Pax-3 inductive activities arising
      from Hensen's node and posterior non-axial mesoderm do not strictly depend on FGF
      or retinoic acid.

PMID- 9169854
TI  - The held out wings (how) Drosophila gene encodes a putative RNA-binding protein
      involved in the control of muscular and cardiac activity.
AB  - In an attempt to identify genes that are involved in Drosophila embryonic cardiac
      development, we have cloned and characterized a gene whose function is required
      late in embryogenesis to control heart rate and muscular activity. This gene has
      been named held out wings (how) because hypomorphic mutant alleles produce adult
      animals that have lost their ability to fly and that keep their wings horizontal
      at a 90 degree angle from the body axis. In contrast to the late phenotype
      observed in null mutants, the How protein is expressed early in the invaginating
      mesoderm and this expression is apparently under the control of twist. When the
      different mesodermal lineages segregate, the expression of How becomes restricted
      to the myogenic lineage, including the cardioblasts and probably all the
      myoblasts. Antibodies directed against the protein demonstrate that How is
      localized to the nucleus. how encodes a protein containing one KH-domain which
      has been implicated in binding RNA. how is highly related to the mouse quaking
      gene which plays a role at least in myelination and that could serve to link a
      signal transduction pathway to the control of mRNA metabolism. The properties of
      the how gene described herein suggest that this gene participates in the control
      of expression of as yet unidentified target mRNAs coding for proteins essential
      to cardiac and muscular activity.

PMID- 9169855
TI  - Induction of cytokine transcripts in the central nervous system and pituitary
      following peripheral administration of endotoxin to mice.
AB  - The regional distribution and inducibility of cytokines in the normal brain is
      still a matter of controversy. As an attempt to clarify this issue, we studied
      the constitutive and induced expression of interleukin (IL)-1beta, IL-6, tumor
      necrosis factor (TNF)-alpha, and interferon (IFN)-gamma mRNAs in the brain,
      pituitary, and spleen of mice using qualitative and semiquantitative reverse
      transcription polymerase chain reaction. The contribution of nonbrain cells to
      the cytokine transcripts detected was considered. With the exception of IFN-gamma
      mRNA, transcripts for the other cytokines were found to be constitutively present
      in the brain. Following i.p. injection of lipopolysaccharide (LPS) at a dose
      below those described to disrupt the blood-brain barrier (BBB), cytokine mRNA
      expression was increased in the spleen, the pituitary, and the brain. In the
      brain, the onset of transcription varied from 45 min (IL-1beta, TNF-alpha) to 4
      hr (IFN-gamma), and the peak of mRNA accumulation was observed at different times
      depending on the cytokine and the brain region studied. IL-1 and IL-6 were highly
      expressed in the hypothalamus and hippocampus, while TNF-alpha expression was
      more marked in the thalamus-striatum. The cortex was the region in which
      cytokines were less inducible. The inducible expression of cytokine mRNAs in the
      brain was paralleled by stimulation of the hypothalamus-pituitary-adrenal axis.
      These results show the capacity of brain cells to synthesize different cytokine
      mRNAs in vivo and define the kinetics of their expression in several brain areas
      and in the periphery in parallel to the activation of a neuroendocrine pathway by
      endotoxin.

PMID- 9169856
TI  - Normal and reactive NG2+ glial cells are distinct from resting and activated
      microglia.
AB  - We have previously used antibodies to the NG2 proteoglycan and the alpha receptor
      for platelet-derived growth factor (PDGF alpha receptor) to identify
      oligodendroglial progenitor cells in vivo and in vitro. It has recently become
      evident that the GD3 antigen, which has been widely used as a marker for
      oligodendrocyte progenitor cells, is also expressed by microglial cells. In this
      study we have examined the relationship between the NG2+/PDGF alpha receptor+
      glial progenitor cells and microglial cells in normal developing and mature rat
      brain and in inflammatory lesions in mice with experimental autoimmune
      encephalomyelitis (EAE). Double-labeling of sections from normal rat brain using
      anti-NG2 antibodies and lectin from Griffonia simplicifolia (GSA I-B4) or
      monoclonal antibody 4H1 indicated that there is no overlap between NG2+ glial
      progenitor cells and microglia in the parenchyma of the central nervous system.
      In EAE lesions, both NG2+ cells and microglia, identified by antibodies to F4/80
      and CD45, displayed reactive changes characterized by increased cell number and
      staining intensity and shortening and thickening of cell processes. Both cell
      types were found surrounding perivascular infiltrates of lymphocytes. Double
      labeling EAE sections for NG2 and F4/80 or CD45 failed to reveal cells that co
      expressed both antigens, suggesting that reactive NG2+ cells are distinct from
      activated microglia. However, a close spatial relationship between NG2+ cells and
      microglia was observed in the normal brain and to a greater extent in EAE, where
      processes of an activated microglial cell were sometimes seen to encircle an NG2+
      cell. These observations are indicative of a functional interaction between
      microglia and the NG2+ glial cells.

PMID- 9169857
TI  - Association of syntaxin with SNAP-25 and VAMP (synaptobrevin) during axonal
      transport.
AB  - Two proteins of the presynaptic plasma membrane, syntaxin and SNAP-25, and a
      synaptic vesicle membrane protein, VAMP/synaptobrevin, form stable protein
      complexes that are involved in the docking and fusion of synaptic vesicles at the
      presynaptic membrane. These protein complexes have also been described in a
      homogeneous population of cholinergic synaptosomes purified from Torpedo electric
      organ. In the present study, we performed similar experiments combining velocity
      sedimentation and immunoprecipitation on control or ligated electric nerves and
      found it was possible to distinguish syntaxin that is in the axonal plasma
      membrane from syntaxin that is transported by the fast anterograde axonal flow.
      Although syntaxin that is resident in axonal membranes is associated with SNAP-25
      but not with VAMP, syntaxin that accumulates proximally to a ligature is
      associated with both SNAP-25 and VAMP in a stoichiometry very similar to that of
      the nerve terminal complex. In control nerves, lower amounts of syntaxin form a
      complex with VAMP, in proportion to syntaxin, which is conveyed by the axonal
      flow. Because added VAMP was unable to associate with syntaxin in solubilized
      control nerves and because neither solubilization by SDS nor dilution to the
      nanomolar range of syntaxin and VAMP concentrations before solubilization change
      the stoiechiometry between the immunoprecipitated proteins, this complex appears
      to be both formed prior to solubilization and stable thereafter. Hence,
      heterotrimeric complexes containing syntaxin, SNAP-25, and VAMP are already
      formed during fast anterograde axonal transport, before reaching the nerve
      endings.

PMID- 9169858
TI  - Cyclic AMP-mediated induction of the glial fibrillary acidic protein is
      independent of protein kinase A activation in rat C6 glioma.
AB  - N6-O'2-dibutyryl cAMP (dbcAMP), N6-monobutyryl cAMP (N6-mbcAMP), 8-Chloro cAMP
      (ClcAMP), and O'2-monobutyryl cAMP (O'2-mbcAMP) were used to study glial
      fibrillary acidic protein (GFAP) induction in rat C6 glioma. With the exception
      of O'2-mbcAMP, these cAMP analogs induced GFAP after stimulation of cells with a
      concentration of 0.5-1 mM. Only dbcAMP and N6-mbcAMP increased the intracellular
      concentration of cAMP. Protein kinase A (PKA) activation is often proposed to be
      involved in GFAP expression in astrocytes. Ion-exchange chromatography indicated
      that protein kinase activity is associated with PKA type II in C6. dbcAMP, N6
      mbcAMP, and ClcAMP upregulated the amount of cAMP-binding proteins approximately
      twofold. RI was upregulated in the cytosol and particulate fraction, whereas RII
      was not affected after stimulation with dbcAMP. Concomitant, the PKA activity
      decreased approximately 60% and 40% in the cytosol and particulate fraction,
      respectively. CREB is constitutively expressed in C6 and is downregulated after
      stimulation with dbcAMP. The membrane-permeable PKA inhibitor N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinoline sulfonamide (H89) did not suppress the
      induction of GFAP-mRNA and its translation into GFAP. On the contrary, depending
      on the time difference between H89 and dbcAMP addition to C6, GFAP synthesis
      could even be potentiated more than twofold. Experiments in the presence of
      cycloheximide showed that protein synthesis is necessary for GFAP transcription.
      Although all components of the PKA signal transduction pathway are present in C6,
      GFAP synthesis is not dependent on PKA activation but required the synthesis of
      an unidentified factor.

PMID- 9169859
TI  - Corticosterone regulates expression of BDNF and trkB but not NT-3 and trkC mRNA
      in the rat hippocampus.
AB  - Corticosterone has profound effects on growth, differentiation, and synaptic
      transmission of hippocampal neurons by activation of mineralocorticoid receptors
      (MRs) and glucocorticoid receptors (GRs). In the present study we tested if
      neurotrophins can be implicated in these effects. For this purpose we injected
      30, 300, and 1,000 microg corticosterone s.c. (per kg body weight) in
      adrenalectomized rats and measured the mRNA levels of brain-derived neurotrophic
      factor (BDNF), tyrosine receptor kinase (trk)B, neurotrophin (NT)-3, and trkC in
      hippocampal cell fields at 6 hr after steroid administration by in situ
      hybridization. NT-3 and trkC mRNA did not show significant changes in any
      hippocampal region after the various doses of corticosterone. BDNF mRNA decreased
      after corticosterone administration dose dependently, resulting in a maximal
      suppression of 35, 20, and 50% in dentate gyrus, CA3, and CA1, respectively.
      Interestingly, trkB responded to corticosterone in an inverted U-shaped fashion
      in CA3 and dentate gyrus: the low dose of corticosterone increased trkB mRNA
      expression in both regions by approximately 30%, while the effect of the two
      higher doses was not different from the vehicle injected controls. In conclusion,
      we found differential effects of low and high doses of corticosterone on BDNF and
      trkB expression in hippocampus, which suggests involvement of a coordinated MR-
      and GR-mediated action.

PMID- 9169860
TI  - Single K channel currents in Schwann cells from normal and neurofibromatosis
      affected damselfish.
AB  - Damselfish neurofibromatosis is a naturally occurring disease of a tropical
      marine fish species. Affected fish exhibit peripheral nerve sheath tumors which
      contain morphologically abnormal Schwann cells (SC), similar to tumors
      encountered in the human disease neurofibromatosis type 1. Unitary A-type K
      channels in cell-attached membrane patches of SC were studied. Three different K
      channel conductances of approximately 5, 10, and 15 pS were present in both
      normal SC (n = 10) and tumored SC (n = 9). The variability in K channel
      conductance coincided with a large range of both mean open time and open
      probability in patches from normal and tumored SC. Channel open time histograms
      were fit by a single exponential. The ranges of time constants for open times
      irrespective of conductance were 0.26-9.3 msec in patches from normal cells and
      0.60-0.73 msec in patches from tumored cells. These ranges were not significantly
      different. Inactivation time constants from ensemble averages of single channel
      currents averaged 83 +/- 46 msec for normal SC and 44 +/- 26 msec for tumored SC,
      which were not significantly different. These results suggest that A-type K
      currents from fish SC are composed of channels exhibiting multiple conductances
      and a variety of inactivation rates, which may account for the range of
      inactivation observed in whole cell currents but whose activity in membrane
      patches may not be wholly applicable to the whole cell currents.

PMID- 9169861
TI  - Immunocytochemical and electron microscope observations on astroglial
      interlaminar processes in the primate neocortex.
AB  - At variance with the rat, previous observations disclosed the presence of long
      interlaminar astroglial processes in the cerebral cortex of adult nonhuman
      primates. To examine its presence in human cerebral cortex, samples of frontal
      and temporal cerebral cortices were obtained during programmed brain surgery from
      a young patient with an intraventricular astrocytoma, and from one young and two
      adult patients with frontal and temporal lobe focal epilepsy, respectively.
      Samples of the visual cortex were also obtained at an autopsy of an 84-year-old
      woman without any known neurological disease. Brain tissues were processed for
      GFAP-IR immunocytochemistry. Long, interlaminar, GFAP-IR astroglial processes of
      usually 300-500 microm, but occasionally reaching almost 1,000 microm, were
      observed. These processes resembled those previously described in the cerebral
      cortex of adult New World monkeys. Available data suggest that they may represent
      a predominant characteristic in postnatal primate cerebral cortex. EM analysis of
      club-like endings disclosed a multilamellar organization of GFAP-IR intermediate
      filaments, and the presence of mitochondria and amorphous, electron dense
      material. Their possible function is yet to be determined.

PMID- 9169862
TI  - Striatal target-induced axonal branching of dopaminergic mesencephalic neurons in
      culture via diffusible factors.
AB  - The effects of striatal target cells on the morphological development of
      dopaminergic neurons were studied in dissociated cultures of embryonic rat
      mesencephalon. Mesencephalic neurons were cultured for four days in presence of
      target striatal cells or non target cerebellar ones. The outgrowth of
      dopaminergic neurons, visualized after tyrosine hydroxylase immunohistochemistry,
      was examined by quantitative morphometry. In cocultures, the increased complexity
      of dopaminergic neurites (branching) was the most striking pattern. It was
      dependent on the presence of target striatal cells as compared to non target
      ones. Cultures raised in presence or absence of serum lead to suggest the
      implication of striatal neurons rather than glia. Using MAP2 and phosphorylated
      neurofilaments immunohistochemistry in combination with tyrosine hydroxylase
      immunolabelling, it could be shown that the target-induced branching effect
      concerned only axonal and not dendritic processes. To further define whether
      diffusible factors from the striatal target would participate in the axonal
      branching effect, mesencephalic cells were cultured in conditioned medium from
      striatal neurons. Striatal conditioned medium enhanced dopamine uptake and
      dopamine neuron branching to the same extent as that observed in striatal
      cocultures. These findings demonstrate that soluble factors secreted by striatal
      neurons themselves selectively influence the branching of dopaminergic axons in
      vitro.

PMID- 9169863
TI  - Inducible nitric oxide synthase and nitric oxide production by oligodendrocytes.
AB  - It has been previously demonstrated that microglia and astrocytes produce
      micromolar amounts of nitric oxide in vitro. In this study, we demonstrate that
      primary rat oligodendrocytes can be stimulated to produce iNOS mRNA as detected
      by Northern blot and in situ hybridization analysis and a 131-kDa iNOS protein by
      Western blot analysis; protein was also detected in cells by single- and double
      label immunohistochemistry for iNOS and the oligodendrocyte-specific marker
      CNPase. NO/NOS are produced as a consequence of activation of the gene encoding
      the inducible nitric oxide synthase as determined by inhibition with actinomycin
      D and cyclohexamide. The iNOS is functional, leading to calcium/calmodulin
      independent NO production in these in vitro cultures.

PMID- 9169864
TI  - The yeast genome directory.

PMID- 9169865
TI  - Overview of the yeast genome.
AB  - The collaboration of more than 600 scientists from over 100 laboratories to
      sequence the Saccharomyces cerevisiae genome was the largest decentralised
      experiment in modern molecular biology and resulted in a unique data resource
      representing the first complete set of genes from a eukaryotic organism. 12
      million bases were sequenced in a truly international effort involving European,
      US, Canadian and Japanese laboratories. While the yeast genome represents only a
      small fraction of the information in today's public sequence databases, the
      complete, ordered and non-redundant sequence provides an invaluable resource for
      the detailed analysis of cellular gene function and genome architecture. In terms
      of throughput, completeness and information content, yeast has always been the
      lead eukaryotic organism in genomics; it is still the largest genome to be
      completely sequenced.

PMID- 9169866
TI  - Genetic and physical maps of Saccharomyces cerevisiae.
AB  - Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are
      presented. The genetic map is the result of 40 years of genetic analysis. The
      physical map was produced from the results of an international systematic
      sequencing effort. The data for the maps are accessible electronically from the
      Saccharomyces Genome Database (SGD: http://genome-www.stanford.
      edu/Saccharomyces/).

PMID- 9169867
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.
AB  - The complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome IV has
      been determined. Apart from chromosome XII, which contains the 1-2 Mb rDNA
      cluster, chromosome IV is the longest S. cerevisiae chromosome. It was split into
      three parts, which were sequenced by a consortium from the European Community,
      the Sanger Centre, and groups from St Louis and Stanford in the United States.
      The sequence of 1,531,974 base pairs contains 796 predicted or known genes, 318
      (39.9%) of which have been previously identified. Of the 478 new genes, 225
      (28.3%) are homologous to previously identified genes and 253 (32%) have unknown
      functions or correspond to spurious open reading frames (ORFs). On average there
      is one gene approximately every two kilobases. Superimposed on alternating
      regional variations in G+C composition, there is a large central domain with a
      lower G+C content that contains all the yeast transposon (Ty) elements and most
      of the tRNA genes. Chromosome IV shares with chromosomes II, V, XII, XIII and XV
      some long clustered duplications which partly explain its origin.

PMID- 9169869
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.
AB  - The complete nucleotide sequence of Saccharomyces cerevisiae chromosome VII has
      572 predicted open reading frames (ORFs), of which 341 are new. No correlation
      was found between G+C content and gene density along the chromosome, and their
      variations are random. Of the ORFs, 17% show high similarity to human proteins.
      Almost half of the ORFs could be classified in functional categories, and there
      is a slight increase in the number of transcription (7.0%) and translation (5.2%)
      factors when compared with the complete S. cerevisiae genome. Accurate
      verification procedures demonstrate that there are less than two errors per
      10,000 base pairs in the published sequence.

PMID- 9169868
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome V.
AB  - Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae
      chromosome V. Analysis of the sequence revealed a centromere, two telomeres and
      271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There
      are two Tyl transposable elements, each of which contains an ORF (included in the
      count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues
      in the public databases, and 112 (41%) are previously characterized yeast genes.

PMID- 9169870
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.
AB  - Large-scale systematic sequencing has generally depended on the availability of
      an ordered library of large-insert bacterial or viral genomic clones for the
      organism under study. The generation of these large insert libraries, and the
      location of each clone on a genome map, is a laborious and time-consuming
      process. In an effort to overcome these problems, several groups have
      successfully demonstrated the viability of the whole-genome random 'shotgun'
      method in large-scale sequencing of both viruses and prokaryotes. Here we report
      the sequence of Saccharomyces cerevisiae chromosome IX, determined in part by a
      whole-chromosome 'shotgun', and describe the particular difficulties encountered
      in the random 'shotgun' sequencing of an entire eukaryotic chromosome. Analysis
      of this sequence shows that chromosome IX contains 221 open reading frames
      (ORFs), of which approximately 30% have been sequenced previously. This
      chromosome shows features typical of a small Saccharomyces cerevisiae chromosome.

PMID- 9169871
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.
AB  - The yeast Saccharomyces cerevisiae is the pre-eminent organism for the study of
      basic functions of eukaryotic cells. All of the genes of this simple eukaryotic
      cell have recently been revealed by an international collaborative effort to
      determine the complete DNA sequence of its nuclear genome. Here we describe some
      of the features of chromosome XII.

PMID- 9169872
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.
AB  - Systematic sequencing of the genome of Saccharomyces cerevisiae has revealed
      thousands of new predicted genes and allowed analysis of long-range features of
      chromosomal organization. Generally, genes and predicted genes seem to be
      distributed evenly throughout the genome, having no overall preference for DNA
      strand. Apart from the smaller chromosomes, which can have substantially lower
      gene density in their telomeric regions, there is a consistent average of one
      open reading frame (ORF) approximately every two kilobases. However, one of the
      most surprising findings for a eukaryote with approximately 6,000 genes was the
      amount of apparent redundancy in its genome. This redundancy occurs both between
      individual ORFs and over more extensive chromosome regions, which have been
      duplicated preserving gene order and orientation. Here we report the entire
      nucleotide sequence of chromosome XIII, the sixth-largest S. cerevisiae
      chromosome, and demonstrate that its features and organization are consistent
      with those observed for other S. cerevisiae chromosomes. Analysis revealed 459
      ORFs, 284 have not been identified previously. Both intra- and interchromosomal
      duplications of regions of this chromosome have occurred.

PMID- 9169874
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.
AB  - Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to
      be discovered. It is the third-largest yeast chromosome after chromosomes XII and
      IV, and is very similar in size to chromosome VII. It alone represents 9% of the
      yeast genome (8% if ribosomal DNA is included). When systematic sequencing of
      chromosome XV was started, 93 genes or markers were identified, and most of them
      were mapped. However, very little else was known about chromosome XV which, in
      contrast to shorter chromosomes, had not been the object of comprehensive genetic
      or molecular analysis. It was therefore decided to start sequencing chromosome XV
      only in the third phase of the European Yeast Genome Sequencing Programme, after
      experience was gained on chromosomes III, XI and II. The sequence of chromosome
      XV has been determined from a set of partly overlapping cosmid clones derived
      from a unique yeast strain, and physically mapped at 3.3-kilobase resolution
      before sequencing. As well as numerous new open reading frames (ORFs) and genes
      encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs
      confirms the high proportion of orphan genes and reveals a number of ancestral
      and successive duplications with other yeast chromosomes.

PMID- 9169875
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.
AB  - The nucleotide sequence of the 948,061 base pairs of chromosome XVI has been
      determined, completing the sequence of the yeast genome. Chromosome XVI was the
      last yeast chromosome identified, and some of the genes mapped early to it, such
      as GAL4, PEP4 and RAD1 (ref. 2) have played important roles in the development of
      yeast biology. The architecture of this final chromosome seems to be typical of
      the large yeast chromosomes, and shows large duplications with other yeast
      chromosomes. Chromosome XVI contains 487 potential protein-encoding genes, 17
      tRNA genes and two small nuclear RNA genes; 27% of the genes have significant
      similarities to human gene products, and 48% are new and of unknown biological
      function. Systematic efforts to explore gene function have begun.

PMID- 9169876
TI  - BSE sets agenda for imported gelatin.

PMID- 9169877
TI  - Baffling skin ailments may originate in psyche.

PMID- 9169878
TI  - Dermatologic disorders diminish quality of life.

PMID- 9169873
TI  - The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
      evolutionary implications.
AB  - In 1992 we started assembling an ordered library of cosmid clones from chromosome
      XIV of the yeast Saccharomyces cerevisiae. At that time, only 49 genes were known
      to be located on this chromosome and we estimated that 80% to 90% of its genes
      were yet to be discovered. In 1993, a team of 20 European laboratories began the
      systematic sequence analysis of chromosome XIV. The completed and intensively
      checked final sequence of 784,328 base pairs was released in April, 1996.
      Substantial parts had been published before or had previously been made available
      on request. The sequence contained 419 known or presumptive protein-coding genes,
      including two pseudogenes and three retrotransposons, 14 tRNA genes, and three
      small nuclear RNA genes. For 116 (30%) protein-coding sequences, one or more
      structural homologues were identified elsewhere in the yeast genome. Half of them
      belong to duplicated groups of 6-14 loosely linked genes, in most cases with
      conserved gene order and orientation (relaxed interchromosomal synteny). We have
      considered the possible evolutionary origins of this unexpected feature of yeast
      genome organization.

PMID- 9169879
TI  - From the Food and Drug Administration.

PMID- 9169880
TI  - From the Centers for Disease Control and Prevention. Availability of diphtheria
      antitoxin through an investigational new drug protocol.

PMID- 9169881
TI  - From the Centers for Disease Control and Prevention. Respiratory diphtheria
      caused by Corynebacterium ulcerans--Terre Haute, Indiana, 1996.

PMID- 9169882
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States and worldwide, 1996-97 season, and composition of the 1997-98
      influenza vaccine.

PMID- 9169883
TI  - A piece of my mind. A child's pain.

PMID- 9169884
TI  - Blinding of clinical trials with concurrent economic analysis.

PMID- 9169885
TI  - Factors contributing to declines in cardiac mortality.

PMID- 9169886
TI  - Clinical crossroads: a 65-year-old man with an inguinal hernia.

PMID- 9169887
TI  - Clinical crossroads: a 65-year-old man with an inguinal hernia.

PMID- 9169888
TI  - Does organic gardening foster foodborne pathogens?

PMID- 9169889
TI  - The paradox of technology: learning to share control with the patient.

PMID- 9169890
TI  - The paradox of technology: learning to share control with the patient.

PMID- 9169891
TI  - Malpractice claims and physicians' communication patterns.

PMID- 9169892
TI  - Malpractice claims and physicians' communication patterns.

PMID- 9169893
TI  - Fatality associated with combined fluoxetine-amitriptyline therapy.

PMID- 9169894
TI  - Thrombolytic therapy for eligible elderly patients with acute myocardial
      infarction.
AB  - OBJECTIVE: To determine the correlates of thrombolytic therapy use in a
      population-based sample of elderly patients hospitalized with acute myocardial
      infarction who were eligible for the therapy on presentation. DESIGN:
      Retrospective cohort study using data from medical charts and administrative
      files. SETTING: All acute care, nongovernmental hospitals in Connecticut.
      PATIENTS: A cohort of 3093 patients aged 65 years and older with a discharge
      diagnosis of acute myocardial infarction covered by Medicare from May 1992 to May
      1993. RESULTS: Among the 753 patients with ST-segment elevation of 1 mm or more
      in at least 2 contiguous leads, left bundle branch block not known to be old, and
      no absolute contraindications to thrombolytic therapy who were not referred for
      direct angioplasty or bypass surgery, 419 patients (56%) did not receive
      thrombolytic therapy. The strongest predictors of not receiving thrombolytic
      therapy included advanced age, absence of chest pain, presentation more than 6
      hours after the onset of symptoms, left bundle branch block, total ST-segment
      elevation of 6 mm or less, presence of Q waves, ST-segment elevation in only 2
      leads, and altered mental status. Physicians documented why they did not
      administer thrombolytic therapy in 19% of the charts. Delay in presentation and
      increased age were the most common reasons cited. Among the subset of 261
      patients who presented with chest pain and within 6 hours of symptoms, 197 (75%)
      received thrombolytic therapy. CONCLUSIONS: Many eligible and ideal patients for
      thrombolytic therapy are not treated. Physicians are less likely to use
      thrombolytic therapy in eligible patients with characteristics associated with an
      increased risk of bleeding, lower-risk infarction, less certain diagnosis, less
      certain efficacy, or altered mental status. These findings suggest that the lack
      of treatment represents a clinical judgment rather than an inadvertent omission.
      In some cases, such as the lower use of thrombolytic therapy with older age,
      these judgments are not consistent with the published literature and may
      represent opportunities to improve care.

PMID- 9169895
TI  - Association of serum lipoprotein(a) levels and apolipoprotein(a) size
      polymorphism with target-organ damage in arterial hypertension.
AB  - OBJECTIVE: To investigate the association between lipoprotein(a) [Lp(a)] and
      other plasma lipids and apolipoproteins and target-organ damage (TOD) in patients
      with arterial hypertension. DESIGN: Cross-sectional study of a case series.
      SETTING: University medical center. PARTICIPANTS: Lipoprotein(a) and
      apolipoproteins were analyzed in 277 untreated patients with mild to moderate
      essential hypertension and in 102 healthy controls. Apolipoprotein(a) [apo(a)]
      phenotypes were additionally analyzed in an independent sample set of 106
      hypertensive and 105 control subjects. MAIN OUTCOME MEASURES: Staging of TOD
      obtained according to World Health Organization guidelines by clinical
      evaluation, and laboratory tests including measurments of creatinine clearance,
      proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and
      ultrasound examination of major arteries; levels of lipids, apolipoproteins,
      Lp(a), fibrinogen, and apo(a) phenotypes. RESULTS: Blood pressure, duration of
      hypertension, and levels of total cholesterol, low-density lipoprotein
      cholesterol, apolipoprotein B, Lp(a), and fibrinogen were significantly related
      to the presence and severity of TOD in univariate analysis. Stepwise multivariate
      analysis showed Lp(a) levels (P<.001) to be the best discriminator of the
      presence of TOD, followed by systolic blood pressure (P<.001), duration of
      hypertension (P=.01), and low-density lipoprotein cholesterol (P=.04). The Lp(a)
      levels were related to TOD independent of the level of blood pressure. We
      confirmed this association between Lp(a) concentrations and severity of TOD in a
      second independent sample set and observed a significantly higher frequency of
      low-molecular-weight apo(a) isoforms with increasing severity of TOD (P=.02).
      CONCLUSIONS: Lipoprotein(a) and apo(a) phenotype are sensitive indicators of the
      severity of TOD in patients with essential hypertension, and their evaluation
      might permit identification of hypertensive subjects liable to the development of
      organ damage. The higher frequency of low-molecular-weight apo(a) isoforms in
      patients with TOD demonstrates a genetically determined risk for the development
      of TOD in hypertensive patients.

PMID- 9169896
TI  - Pediatric window-cord strangulations in the United States, 1981-1995.
AB  - OBJECTIVE: To document the prevalence of pediatric asphyxial death from window
      covering cords in the United States and identify associated risk factors. DESIGN:
      Retrospective analysis of existing death certificate and incident files compiled
      by the US Consumer Product Safety Commission. SETTING: United States, 1981
      through 1995. PATIENTS: Children aged 1 month to 8 years suffering unintentional
      traumatic asphyxiation from a window-covering cord. RESULTS: A total of 183 fatal
      window-cord strangulations were reported for the years 1981 through 1995,
      representing a mortality rate of 0.14 (95% confidence interval [CI], 0.10-0.18)
      per 100000 persons (< or =3 years old) per year in the United States. Ninety
      three percent of victims were 3 years of age or younger. Pull cords on venetian
      type horizontal window coverings accounted for 86% of documented injuries. Infant
      victims were more likely to become entangled while put down for a nap and
      toddlers were more likely to be suspended by the cord after falling or jumping
      from a height (P=.002). Window coverings remained anchored and did not undrape
      when substantial weight was suspended in the draw-cord loop. CONCLUSIONS: Window
      covering cords represent a substantial strangulation hazard compared with other
      potentially harmful household products that were modified based on voluntary
      standards to mitigate the risk of injury. Product design modifications and
      parental education will be necessary to avert this type of fatal home injury.

PMID- 9169897
TI  - Initial employment status of resident physicians completing training in 1995.
AB  - OBJECTIVE: To assess the degree and type of difficulty encountered by resident
      physicians attempting to enter the workforce in 1995. DESIGN: Employment
      information derived from a 1-page descriptive survey completed by residency
      program directors from January 1, 1996, to June 15,1996, is described and
      compared with the results of a similar survey completed 1 year earlier. SETTING:
      Directors of 4568 residency programs in 31 specialties and subspecialties
      accredited by the Accreditation Council for Graduate Medical Education. MAIN
      OUTCOME MEASURE: The number of 1995 program graduates, their current professional
      status, and program directors' characterization of the experience of graduates
      who entered clinical practice, including the number who experienced major
      difficulties securing an acceptable practice position. Program directors reported
      actual and anticipated decreases in the number of residency positions and the
      likely availability of future professional opportunities. RESULTS: The 3819
      program directors (83.6%) who completed the survey reported that 20065 resident
      physicians completed a residency program during 1995. Of those seeking employment
      (n = 13215), most entered clinical practice (80.1%) or took an academic position
      (15.6%); 2.2% were unemployed or had taken a position in a specialty or
      subspecialty different from the one in which they were last trained. A portion
      (6.3%) of graduates who entered clinical practice in their specialty or
      subspecialty experienced difficulty finding a suitable position; the percentage
      was lowest among graduates of general surgery, psychiatry, and primary care
      specialties. CONCLUSIONS: Survey results regarding the 1995 graduates are
      consistent with those obtained regarding the 1994 graduates and suggest that the
      market for physician services in some disciplines continues to be restrictive. We
      found that graduates of the specialties of anesthesiology and plastic surgery,
      whom we reported had the greatest difficulty finding acceptable positions in
      1994, had less difficulty in 1995, suggesting a possible improvement in the
      market, less competition, a change in the respondents' perception of
      "acceptable," or a change in the resident physicians' willingness to pursue
      different opportunities. The general consistency of our results and their
      congruence with other published data suggest that this method is useful to
      identify and monitor trends in the physician market.

PMID- 9169898
TI  - Does it make clinical sense to equate terminally ill patients who require life
      sustaining interventions with those who do not?
AB  - Two US courts of appeals have ruled that competent, terminally ill patients have
      a constitutional right to physician-assisted suicide. The cases are now before
      the US Supreme Court, which is expected to issue a ruling later this year. This
      article analyzes the keystone of the courts' ruling: their assertion that
      competent, terminally ill patients who are being kept alive on life support are
      equivalent to competent, terminally ill patients who do not require such support.
      Because the former are permitted to end their lives by refusing treatment, the
      courts found that the latter also have a right to determine the time and manner
      of their death, through prescriptions for lethal doses of medication. This
      article analyzes whether the courts' thinking is premised on a clinically
      plausible view of the care of terminally ill patients. Based on a discussion of
      common situations involving terminal illness, we argue that the courts' reasoning
      is deeply flawed. The article also analyzes how the implications of the courts'
      reasoning might undermine the care of terminally ill patients.

PMID- 9169899
TI  - Determination of deltoid fat pad thickness. Implications for needle length in
      adult immunization.
AB  - OBJECTIVE: To measure deltoid fat pad thickness and determine the optimal needle
      length for deltoid intramuscular immunization in healthy adults. DESIGN, SETTING,
      AND PARTICIPANTS: Prospective study of 220 healthy health care workers (126
      women, 94 men) at the Mayo Medical Center, Rochester, Minn. MAIN OUTCOME
      MEASURES: Deltoid fat pad thickness determined by high-resolution ultrasound
      scanning, weight, height, and mid-deltoid arm circumference. RESULTS: We found a
      highly significant difference between women and men in deltoid fat pad thickness,
      with women having a thicker deltoid fat pad (11.7 vs 8.3 mm; P<.001). Women had a
      greater deltoid skin-fold thickness than men (34.7 vs 17.2 mm, P<.001) and an
      equal body mass index. According to the ultrasound findings, a standard 16-mm
      (5/8-in) needle would not have reached 5 mm into muscle in 17% (16/94) of men and
      48.4% (61/126) of women in this study. CONCLUSIONS: Among healthy adults of the
      age range we studied, the following needle lengths appear to be appropriate for
      true deltoid intramuscular immunization: For men across the weight ranges we
      studied (59-118 kg), use of a 25-mm (1-in) needle would result in at least 5 mm
      of muscle penetration in all subjects. For women who weighed less than 60 kg, a
      16-mm (5/8-in) needle would be sufficient to achieve muscle penetration of 5 mm.
      For women between 60 and 90 kg, a 25-mm (1-in) needle would be sufficient, and
      women greater than 90 kg would require a 38-mm (1.5-in) needle to ensure
      intramuscular administration.

PMID- 9169900
TI  - Can the clinical examination diagnose left-sided heart failure in adults?
AB  - We systematically reviewed the literature to ascertain how well clinicians
      determine the probability and type of left-sided heart failure in their patients.
      Left-sided heart failure is characterized by decreased left ventricular ejection
      fraction or increased filling pressure. The type of heart failure determines
      optimal treatment. Systolic dysfunction exists when ejection fraction is reduced.
      Diastolic dysfunction is presumed to be present when filling pressure is
      increased with a normal ejection fraction and without another explanatory
      diagnosis. Many findings are associated with heart failure, and wide variation
      exists in clinicians' ability to detect these findings. The best findings for
      detecting increased filling pressure are jugular venous distention and
      radiographic redistribution. The best findings for detecting systolic dysfunction
      are abnormal apical impulse, radiographic cardiomegaly, and q waves or left
      bundle branch block on an electrocardiogram. Diastolic dysfunction is especially
      difficult to diagnose, but is associated with an elevated blood pressure during
      heart failure.

PMID- 9169901
TI  - Physician-assisted suicide and euthanasia in the Netherlands. Lessons from the
      Dutch.

PMID- 9169902
TI  - Coronary thrombolysis for the elderly. Is clinical practice really lagging behind
      evidence of benefit?

PMID- 9169903
TI  - Tobacco use in Vietnam. Prevalence, predictors, and the role of the transnational
      tobacco corporations.
AB  - OBJECTIVE: To describe tobacco use in Vietnam and the impact of transnational
      tobacco corporations there. DESIGN: In cities, a multistage cluster design; in
      communes, a systematic sample design, using face-to-face interviews in all sites.
      SETTING: Hanoi, Ho Chi Minh City, and 2 rural communes in Vietnam. PARTICIPANTS:
      Random samples totaling 2004 men and women aged 18 years or older. MAIN OUTCOME
      MEASURES: Prevalence and correlates of tobacco smoking, amount and duration of
      smoking, age at initiation, quitting behavior, knowledge of health hazards of and
      attitudes toward smoking, and cigarette brand smoked, preferred, and recognized
      as most widely advertised. RESULTS: Smoking prevalence among men (n=970) was
      72.8% and 4.3% among women (n=1031). Male smokers had smoked a mean of 15.5
      years; the median age at initiation was 19.5 years. Among male smokers, 16%
      smoked non-Vietnamese cigarettes. More than twice as many (38%), however, said
      that they would prefer to smoke a non-Vietnamese brand if they could afford the
      cost. Among those who recalled any cigarette advertising (38%), 71% recalled a
      non-Vietnamese brand as the most commonly advertised. Male smokers who were
      significantly more likely to smoke non-Vietnamese brands lived in the south, were
      engaged in blue collar or business/service occupations, earned higher incomes,
      and lived in urban areas. CONCLUSIONS: Vietnam has the highest reported male
      smoking prevalence rate in the world. Unless forceful steps are taken to reduce
      smoking among men and prevent the uptake of smoking by youth and women, Vietnam
      will face a tremendous health and economic burden in the near future.
      Implementation of a comprehensive national tobacco control campaign together with
      international regulation will be the keys to the eradication of the tobacco
      epidemic in Vietnam and throughout the developing world.

PMID- 9169904
TI  - Bovine spongiform encephalopathy (BSE): causes and consequences of a common
      source epidemic.
AB  - Bovine spongiform encephalopathy (BSE) is a transmissible spongiform
      encephalopathy (TSE) or prion disease of cattle first recognized in 1986 in the
      United Kingdom, where it produced a common source epidemic that peaked in January
      1993 and has subsided markedly since that time. The epidemic began simultaneously
      at many geographic locations and was traced to contamination of meat and bone
      meal (MBM), a dietary supplement prepared from rendering of slaughterhouse offal.
      It appears that the epidemic was initiated by the presence of the agent of
      scrapie (a long-standing TSE of sheep) that was first transmitted to cattle,
      beginning in the early 1980s, when most rendering plants abandoned the use of
      organic solvents in the preparation of MBM. The epidemic was probably accelerated
      by the recycling of infected bovine tissues prior to the recognition of BSE. To
      terminate the epidemic, a prohibition on the feeding of ruminant-derived protein
      to ruminants was introduced in the United Kingdom in July 1988. The ruminant feed
      ban accounts for the decline of the epidemic after an interval of about 5 years,
      approximately equivalent to the average incubation period of BSE. Relatively few
      cases of BSE have occurred in cattle born after 1993, and it is predicted that
      the epidemic will terminate about the year 2000 based on an extrapolation of the
      present declining curve. A comparison of data from the United Kingdom with data
      from relatively low incidence countries, such as Switzerland, indicates that this
      epidemic has been mainly confined to the United Kingdom because of a unique
      concatenation of risk factors, including: 1) a high ratio of sheep to cattle; 2)
      a relatively high rate of endemic scrapie; 3) the heavy feeding of MBM to dairy
      cattle; and 4) changes in the rendering process used to prepare MBM. Recently,
      cases of a variant form of Creutzfeldt-Jakob disease (a TSE of humans) have been
      reported in the United Kingdom. These cases, at least 10 of which had onset in
      1994-1995, are distinguished by their occurrence in subjects under age 40 years,
      by their clinical presentation, and by their neurohistopathologic picture. The
      appearance of this novel disease and its concentration in the United Kingdom have
      raised the question that it might represent the transmission of BSE to humans.
      However, the cases gave no history indicating an unusual exposure to live cattle,
      to the preparation of beef products, or of dietary exposure to bovine tissues,
      and it remains to be determined whether they are associated with BSE.

PMID- 9169905
TI  - Epidemiology of insulin-like growth factor-I in elderly men and women. The Rancho
      Bernardo Study.
AB  - Insulin-like growth factor-I (IGF-I) is abundant in the circulation and has been
      shown to have a wide array of biologic effects. The authors carried out a cross
      sectional community-based study of 420 men and 419 nonestrogen-using
      postmenopausal women aged 50-97 years to ascertain the within-person and
      laboratory reliability of IGF-I measurements, and the association of IGF-I with
      common epidemiologic confounders. There was no evidence of seasonal or diurnal
      variation. IGF-I decreased linearly with age in both sexes, with significantly
      higher levels in men than women (134.1 microg/liter vs. 126.9 microg/liter; p =
      0.03) [corrected]. In age-adjusted analyses, IGF-I was not associated with
      height, total or central body fat, lean body mass, current smoking, physical
      activity, or commonly used medications. By contrast, in both men and women who
      reported any alcohol use, IGF-I levels were significantly higher compared with
      those in men and women who reported no alcohol use, and alcohol as a continuous
      variable showed a significant positive linear trend in men (p = 0.0007). The
      authors conclude that IGF-I varied significantly only with age, sex, and alcohol
      use. The minimal number of confounding variables, good reliability, and little
      intraindividual variation suggest that IGF-I should be suitable for epidemiologic
      research.

PMID- 9169906
TI  - Exercise intensity and subclinical cardiovascular disease in the elderly. The
      Cardiovascular Health Study.
AB  - The authors assessed the cross-sectional association between intensity of
      exercise in later life and coronary heart disease risk factors and subclinical
      disease among 2,274 men and women, 65 years of age and older, who were
      participants in the Cardiovascular Health Study (CHS) during 1989-1990. Subjects
      were free of prior clinical cardiovascular disease or impairment of physical
      function. Exercise intensity was characterized as low, moderate, or high, based
      on highest intensity exercise reported over the 2 weeks prior to the CHS baseline
      examination. After adjustment for age, education, and postmenopausal hormone
      therapy (among women), there was an inverse dose-response relationship of
      exercise intensity with selected risk factors. By low, moderate, and high
      exercise intensity, respectively: fasting insulin-men, 15.6 microU/ml, 14.1
      microU/ml, and 12.6 microU/ml, p for trend <0.001; women, 14.8 microU/ml, 13.8
      microU/ml, and 12.0 microU/ml, p for trend = 0.01; serum fibrinogen-men, 316.2
      mg/dl, 315.4 mg/dl, and 300.0 mg/dl, p for trend = 0.01; women, 327.3 mg/dl,
      317.0 mg/dl, and 310.7 mg/dl, p for trend = 0.01; lower extremity arterial
      disease by percent with ankle-arm index <0.9-men, 18.3, 5.5, and 3.7, p for trend
      = 0.01; women, 10.0, 5.7, and 2.8, p for trend = 0.02; evidence of myocardial
      injury by cardiac infarction/injury score (CIIS)-men, 8.0, 6.0, 3.9, p for trend
      <0.001; women, 4.6, 3.9, and 3.6, p for trend = 0.03. Adjustment for smoking,
      alcohol consumption, and total kilocalories expended in exercise altered the
      findings only slightly. The authors conclude that intensity of exercise in later
      life is associated with favorable coronary disease risk factor levels and a
      reduced prevalence of several markers of subclinical disease.

PMID- 9169907
TI  - No increased mortality in later life for cohorts born during famine.
AB  - Nutrition early in life may influence adult mortality. The fetal-origins
      hypothesis suggests that nourishment before birth and during the individual's
      infancy programs the development of risk factors for several important diseases
      of middle and old age. The present study was designed to evaluate the impact of
      extreme nutritional deprivation in utero and during infancy and early childhood
      on mortality in later life. The authors analyzed the survival of the cohorts born
      in Finland during the severe 1866-1868 famine and during the 5 years immediately
      preceding and 5 years immediately following the famine. The study included
      331,932 individuals born prior to the famine, 161,744 born during the famine, and
      323,321 born after the famine. The authors assessed survival by cohorts from
      birth to age 17 years and from age 17 to 40, 60, and 80 years, as well as average
      length of life after age 80 years. Survival from birth to age 17 years was
      significantly lower in cohorts born before and during the famine than in the
      cohorts born after the famine (males, 0.566 vs. 0.671, a difference of 0.105 (95%
      confidence interval (CI) 0.102-0.108); females, 0.593 vs. 0.692, a difference of
      0.099 (95% CI 0.096-0.102)). At subsequent ages, including old age, mortality was
      practically identical in the famine-born cohorts and in the five cohorts born
      before and after the crisis. For both males and females, survival from 17 to 80
      years and mean remaining lifetime at age 80 years were very similar across the 13
      cohorts studied. These findings suggest that, although cohorts subjected to
      prolonged and extreme nutritional deprivation in utero and during infancy and
      early childhood suffer an immediate rise in mortality, after the crisis has
      passed, they carry no aftereffects that influence their survival in later life.

PMID- 9169908
TI  - Misclassification bias in estimates of bereavement effects.
AB  - Prospective studies that examine marital status differences in health and
      mortality frequently fail to update information on marital status in statistical
      models. The authors illustrate how the resulting misclassification of marital
      status can produce substantial bias in estimates of bereavement effects
      associated with widowhood. They use as their main source of data the Longitudinal
      Study of Aging (LSOA), 1984-1990, a national survey of persons aged 70 years and
      older. The estimates are based primarily on 3,192 respondents who were married
      and cohabiting with their spouses at the time of the baseline survey and who
      could be matched to their spouses' records. Comparisons of widowhood status
      derived from matched spouse records with reported marital status recorded in LSOA
      interviews demonstrate that reliance on interview information leads to
      substantial misclassification of marital status. Results from survival models
      indicate that estimates of marital status effects are sensitive to whether and
      how marital status is updated after baseline interviews. For example, updating
      marital status in hazard models from interview information alone indicates a
      protective effect of widowhood, whereas classifying widowhood on the basis of
      spouses' death records reveals a significant bereavement effect (relative
      mortality risks between 1.3 and 1.4).

PMID- 9169909
TI  - Correcting for measurement error in the analysis of case-control data with
      repeated measurements of exposure.
AB  - The authors present a technique for correcting for exposure measurement error in
      the analysis of case-control data when subjects have a variable number of
      repeated measurements, and the average is used as the subject's measure of
      exposure. The true exposure as well as the measurement error are assumed to be
      normally distributed. The method transforms each subject's observed average by a
      factor which is a function of the measurement error parameters, prior to fitting
      the logistic regression model. The resulting logistic regression coefficient
      estimate based on the transformed average is corrected for error. A bootstrap
      method for obtaining confidence intervals for the true regression coefficient,
      which takes into account the variability due to estimation of the measurement
      error parameters, is also described. The method is applied to data from a nested
      case-control study of hormones and breast cancer.

PMID- 9169910
TI  - Body size and risk of breast cancer.
AB  - The relation between body size and breast cancer remains uncertain, particularly
      with regard to differences between pre- and postmenopausal women. The authors
      examined whether height, weight, body mass index, and weight change were
      associated with breast cancer risk among pre- and postmenopausal women. This
      population-based case-control study included women aged 20-74 years (n = 6,548)
      who were diagnosed with invasive breast cancer during 1988-1991 in Maine,
      Massachusetts, New Hampshire, and Wisconsin. Similarly aged control women (n =
      9,057) were selected at random from driver's license files and Health Care
      Financing Administration files. Height, weight, and information on other breast
      cancer risk factors were ascertained by telephone interview, and logistic
      regression was used to estimate multivariate-adjusted odds ratios and 95%
      confidence intervals. Among premenopausal women, the adjusted odds ratio for the
      upper quintile group of height relative to the lowest was 1.36 (95% confidence
      interval (CI) 1.05-1.76). The heaviest premenopausal women had a lower risk (odds
      ratio (OR) = 0.87, 95% CI 0.70-1.10). Among postmenopausal women, the adjusted
      odds ratios were higher for the upper quintile categories of both height (OR =
      1.27, 95% CI 1.11-1.45) and weight (OR = 1.57, 95% CI 1.37-1.79). Weight gain
      since ages 18 and 35 years was associated with increased postmenopausal breast
      cancer risk, and risk was lower in women who had lost weight. These findings
      suggest that programs to avoid weight gain merit study as a means to reduce risk
      of postmenopausal breast cancer.

PMID- 9169911
TI  - Melanocytic nevi and risk of cutaneous malignant melanoma in southern Spain.
AB  - The main objective of this study was to assess whether cutaneous malignant
      melanoma (CMM) shows a stronger relation with the melanocytic nevi count at the
      site where CMM was diagnosed than with the melanocytic nevi count at other sites,
      stratifying by histologic CMM type, in a southern Mediterranean population. Cases
      and controls were selected from a population in southern Spain in 1988-1993. The
      study population included 116 incident cases with non-familial CMM (International
      Classification of Diseases 9th Revision (ICD-9) code 172), and 116 controls
      matched 1:1 for sex and age (+/- 4 years). Data were collected by personal
      interview, and melanocytic nevi were counted over the entire body surface by
      clinical skin examination performed by a dermatologist. Crude and multiple risk
      factor-adjusted odds ratios and 95% confidence intervals were computed by
      conditional logistic regression analysis. After adjustment by skin type,
      unexposed skin color, and sun exposure, CMM was found to occur significantly more
      frequently in individuals with a high number of melanocytic nevi at the same site
      where CMM originated (odds ratio (OR) for >8 nevi = 12.0, 95% confidence interval
      (CI) 1.3-108.2). The ability to predict the number of melanocytic nevi on
      different anatomic sites on CMM, but excluding the CMM cases on each
      corresponding site, was also examined. A significant trend with the number of
      nevi on the anterior surface of thighs was found (OR for >4 nevi = 4.5, 95% CI
      1.4-14.9). Melanocytic nevi count on the melanoma site was the variable most
      closely related to superficial spreading melanoma subtype (SSM) (OR for >8 nevi =
      82.19, 95% CI 2.72-2,454). On the other hand, the number of melanocytic nevi on
      the melanoma site was unrelated to risk of CMM subtypes other than SSM. These
      results support the hypothesis that nevi are an important risk factor for
      melanoma, especially SSM, in populations with a darker ethnic background.

PMID- 9169912
TI  - Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to
      risk of breast cancer in postmenopausal women.
AB  - The authors examined the relation between postmenopausal serum levels of
      testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequent risk of
      breast cancer in a case-control study nested within the New York University
      Women's Health Study cohort. A specific objective of their analysis was to
      examine whether androgens had an effect on breast cancer risk independent of
      their effect on the biologic availability of estrogen. A total of 130 cases of
      breast cancer were diagnosed prior to 1991 in a cohort of 7,054 postmenopausal
      women who had donated blood and completed questionnaires at a breast cancer
      screening clinic in New York City between 1985 and 1991. For each case, two
      controls were selected, matching the case on age at blood donation and length of
      storage of serum specimens. Biochemical analyses were performed on sera that had
      been stored at -80 degrees C since sampling. The present report includes a subset
      of 85 matched sets, for whom at least 6 months had elapsed between blood donation
      and diagnosis of the case. In univariate analysis, testosterone was positively
      associated with breast cancer risk (odds ratio (OR) for the highest quartile =
      2.7, 95% confidence interval (CI) 1.1-6.8, p < 0.05, test for trend). However,
      after including % estradiol bound to sex hormone-binding globulin (SHBG) and
      total estradiol in the statistical model, the odds ratios associated with higher
      levels of testosterone were considerably reduced, and there was no longer a
      significant trend (OR for the highest quartile = 1.2, 95% CI 0.4-3.5).
      Conversely, breast cancer risk remained positively associated with total
      estradiol levels (OR for the highest quartile = 2.9, 95% CI 1.0-8.3) and
      negatively associated with % estradiol bound to SHBG (OR for the highest quartile
      = 0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These
      results are consistent with the hypothesis that testosterone has an indirect
      effect on breast cancer risk, via its influence on the amount of bioavailable
      estrogen. No evidence was found of an association between DHEAS and risk of
      breast cancer in postmenopausal women.

PMID- 9169913
TI  - Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic
      chronic hepatitis B virus carriers.
AB  - The authors conducted a study to assess the importance of underlying liver
      cirrhosis in the development of hepatocellular carcinoma (HCC) and the
      multifactorial etiology of liver cirrhosis in chronic carriers of hepatitis B
      virus (HBV). Between November 1980 and May 1990, all male hepatitis B surface
      antigen (HBsAg) carriers who routinely attended a clinic for asymptomatic HBV
      carriers at the Liver Unit of Chang-Gung Memorial Hospital, Taiwan, were enrolled
      in the study (n = 1,506). The authors used this cohort to investigate
      prospectively for liver cirrhosis and HCC at 6-month intervals by means of
      ultrasonography and clinical assessment. There were 16 incident cases of HCC and
      89 cases of liver cirrhosis (78 of whom were detected during follow-up)
      identified after an average follow-up of 7.1 years. Subclinical liver cirrhosis
      diagnosed by ultrasonography was significantly associated with the risk for HCC
      (multivariate-adjusted relative risk (RR) = 11.8, 95% confidence interval (CI)
      3.9-35.8). By multivariate analysis, the significant risk factors found for liver
      cirrhosis in HBsAg carriers were age, hepatitis B e antigen (HBeAg) carrier
      status, chronic hepatitis manifested by sustained elevated serum aminotransferase
      levels for > or = 6 months, cigarette smoking, non-A blood types, and low
      educational levels. Habitual alcohol drinking was not independently related to
      liver cirrhosis. However, the risk of liver cirrhosis associated with smoking was
      more striking among drinkers than nondrinkers (> or = 20 cigarettes/day vs.
      nonsmokers: drinkers, RR = 9.3, 95% CI 1.1-78.8; nondrinkers, RR = 1.85, 95% CI
      0.98-3.51), which suggests a possible modification effect of alcohol drinking on
      the liver cirrhosis risk of cigarette smoking. The authors observed synergistic
      effects on liver cirrhosis development for cigarette smoking with HBeAg carrier
      status and chronic hepatitis.

PMID- 9169914
TI  - Low cord blood pneumococcal immunoglobulin G (IgG) antibodies predict early onset
      acute otitis media in infancy.
AB  - Low maternally derived serum immunoglobulin G (IgG) antibodies to Streptococcus
      pneumoniae capsular polysaccharides (PS) combined with the inability of infants
      to produce anti-PS antibody may explain onset of otitis media in the first 6
      months of life. To explore this relation, cord blood samples were assayed for
      anti-PS IgG antibodies from 414 of 592 infants enrolled in a study of early onset
      otitis media between 1991 and 1994. Infants' ears were examined at health
      supervision and illness visits for the first 6 months of life in a large
      Minneapolis-St. Paul, Minnesota, health maintenance organization. Antibodies to
      seven common pneumococcal serotypes (3, 4, 6B, 14, 18C, 19F, and 23F) were
      measured by enzyme-linked immunoabsorbent assay (ELISA). Cox's regression
      analysis revealed that among infants with a sibling otitis media history, those
      with low concentrations of type 14 or 19F anti-PS cord blood antibody had earlier
      otitis media onset than those with higher cord blood antibody concentrations
      (relative risks (RR) (95% confidence intervals (CI)) = 1.77 (1.05-2.99) and 1.89
      (1.11-3.23), respectively). Day care attendance also increased risk (RR = 1.56,
      95% CI 0.96-2.52). Breastfeeding, parental smoking, and low anti-PS antibody to
      pneumococcal serotypes 3, 4, 6B, 18C, and 23F did not significantly affect the
      risk of early otitis media.

PMID- 9169915
TI  - Signal transduction pathways activated by ciliary neurotrophic factor and related
      cytokines.
AB  - Neuropoietic cytokines such as ciliary neurotrophic factor, leukemia inhibitory
      factor, and interleukin-6 are known to be responsible for a wide variety of
      effects on cells of the immune and nervous systems. The mechanisms by which such
      diverse effects are regulated and coordinated within cells is of central
      importance to the understanding of how these molecules function during
      development. This review discusses the receptor complexes through which
      neuropoietic cytokines signal and the mechanisms by which activation of specific
      enzymes such as the Jak family of kinases are transduced into changes of gene
      expression through molecules such as the Stat proteins. This review also
      discusses how this JAK-Stat signaling pathway is thought to interact with other
      known cascades, such as the mitogen-activated protein kinase pathway.

PMID- 9169916
TI  - Extrinsic signals in the developing nervous system: the role of neurokines during
      neurogenesis.
AB  - Vertebrate neurogenesis involves many distinct differentiation stages that are
      regulated by extrinsic signals. Survival and differentiation effects on cultured
      neurons of several lineages are elicited by members of the neurokine family of
      growth factors, ciliary neurotrophic factor (CNTF) and the related avian factor,
      growth promoting activity (GPA). The selective actions of these factors are
      mediated through the activation of heteromeric receptor complexes and depend on
      the presence of the ligand-binding receptor subunits CNTFR alpha and GPAR alpha.
      The in vivo localization of CNTFR alpha and GPAR alpha is consistent with the
      previously assigned biological functions but also suggest novel functions for
      these receptors and their ligands during neurogenesis.

PMID- 9169917
TI  - Leukemia inhibitory factor and ciliary neurotrophic factor in sensory neuron
      development.
AB  - Leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), and related
      proteins are potentially involved in several aspects of sensory neuron
      development. There is evidence that LIF promotes the differentiation of sensory
      neurons from progenitor cells of neural crest origin. Later in development, LIF,
      CNTF, oncostatin M and interleukin-6 promote the survival of cultured neurons.
      Some neurons, like those of the nodose ganglion, respond early in their
      development to these factors, whereas other neurons, like those of the trigeminal
      ganglion, respond much later. In addition to promoting sensory neuron survival,
      there is some evidence that LIF is able to influence neurotransmitter and
      neuropeptide expression in these neurons. These observations suggest that several
      kinds of sensory neurons may be influenced in various ways by LIF and related
      factors at different stages of their development.

PMID- 9169918
TI  - Regulation of oligodendrocyte cell survival and differentiation by ciliary
      neurotrophic factor, leukemia inhibitory factor, oncostatin M, and interleukin-6.
AB  - The regulation and maintenance of developmental lineages by trophic factors, both
      cell-mediated and soluble, is a key aspect of cellular differentiation in the
      nervous system. In this review we focus on oligodendrocytes and their progenitors
      and how differentiation and survival are regulated by four neuropoietic
      cytokines: ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M,
      and interleukin-6 (IL-6). We discuss how these cytokines act as "broad spectrum"
      factors. That is, how, even within a specific cell lineage, a given cytokine may
      have different effects on the target cells at various stages of differentiation.

PMID- 9169919
TI  - The development of cholinergic sympathetic neurons: a role for neuropoietic
      cytokines?
AB  - The sympathetic neurons that innervate eccrine sweat glands undergo a phenotypic
      switch from noradrenergic to cholinergic and peptidergic. The changes in
      neurotransmitter choice are retrogradely specified by interactions with the
      target tissue that are mediated by a secreted differentiation factor. Production
      of the target-derived differentiation factor requires noradrenergic innervation.
      The switch from noradrenergic to cholinergic and peptidergic is reproduced in
      culture when neonatal sympathetic neurons are treated with members of the
      neuropoietic cytokine family, leukemia inhibitory factor (LIF) or ciliary
      neurotrophic factor (CNTF), suggesting that these cytokines might be responsible
      for the target-induced change in neurotransmitter properties. Analysis of
      transgenic mice that lack either LIF or CNTF or both, however, does not support
      their candidacy: the transmitter properties of the sweat gland innervation is
      indistinguishable from that of wild-type mice. It seems likely that another and
      novel member of the, family is responsible.

PMID- 9169920
TI  - Ciliary neurotrophic factor as a motor neuron trophic factor.
AB  - The survival of developing motor neurons has long been known to depend on contact
      with target muscle. This observation caused an intensive search for motor neuron
      trophic factors. During that search, a surprisingly large number of factors,
      including neurotrophins, glia-derived neurotrophic factor, fibroblast growth
      factors, and ciliary neurotrophic factor (CNTF) were found to promote motor
      neuron survival in vitro. The present review article examines in detail the
      evidence concerning the potential motor neuron trophic role of CNTF in vivo. The
      main conclusion of the article is that CNTF likely functions as a maintenance and
      repair factor for adult motor neurons and is less likely to play a significant
      developmental role. In addition, the article reviews the literature concerning
      the use of CNTF for treating motor neuron diseases and possible side effects of
      such treatment.

PMID- 9169921
TI  - Changes in neuropeptide phenotype after axotomy of adult peripheral neurons and
      the role of leukemia inhibitory factor.
AB  - Adult peripheral neurons undergo dramatic shifts in gene expression following
      axotomy that are collectively referred to as the cell body reaction. Changes in
      neuropeptide expression are a prominent feature of these axotomized neurons. For
      example, while sympathetic, sensory, and motor neurons do not normally express
      the neuropeptides galanin and vasoactive intestinal peptide, they begin to do so
      within days after axotomy. In contrast, the expression of other peptides, which
      these neurons normally express, such as neuropeptide Y in sympathetic neurons and
      substance P in sensory neurons, is decreased. Recent studies in sympathetic
      neurons have demonstrated that leukemia inhibitory factor plays an important role
      in triggering these changes in neuropeptide phenotype in adult neurons. Future
      studies will be directed at determining to what extent LIF triggers the many
      other changes in gene expression after sympathetic axotomy and whether this
      cytokine plays a similar role in sensory and motor neurons.

PMID- 9169922
TI  - Does ciliary neurotrophic factor serve a different function in the rat versus the
      chicken?
AB  - Ciliary neurotrophic factor (CNTF) was first identified as a trophic activity
      that was able to support the survival of chick ciliary ganglion (CG) neurons in
      vitro. CNTF from rabbit and rat were subsequently purified from sciatic nerve and
      their cDNA sequences cloned. Another trophic molecule for CG neurons was
      identified as a growth promoting activity (GPA). GPA was purified from chicken
      sciatic nerve and cloned from embryonic chicken eye. The rat and rabbit CNTFs
      have a considerable amount of structural homology and are not secreted in
      significant quantities, whereas GPA is less similar in that it is only 49%
      homologous with rabbit and rat CNTF and is secreted by cells. This review
      discusses other similarities and differences in biological activities, molecular
      structure, receptor signaling and cellular distribution between CNTF and GPA and
      suggests that these molecules may have different functions in rodents and birds.

PMID- 9169923
TI  - Are there more members of the CNTF-GPA family?
AB  - Ciliary neurotrophic factor (CNTF) and growth promoting activity (GPA) are two
      members of a family of structurally and functionally related cytokines. Although
      the primary sequences of these proteins are only distantly related, many share
      striking functional similarities. The question of the potential existence of
      more, as yet undiscovered, members of this family, especially those most related
      to CNTF, is discussed. There are several biological systems which exhibit
      unexplained CNTF-like activities. This has led to speculation that there are
      indeed other CNTF-like proteins to be found. Because of the poor primary sequence
      conservation among known members of this family, even those sharing strong
      functional similarities, it is unlikely that a cloning approach based on sequence
      homology will find these putative new members of the family. Instead, a more
      biological approach, based on functional similarities, is more likely to succeed.

PMID- 9169924
TI  - Deposition of monodisperse particles in hollow models representing adult and
      child-size tracheobronchial airways.
AB  - A series of experiments was performed to determine deposition efficiencies of
      four sizes of radiolabeled monodisperse particles in custom-made hollow
      tracheobronchial models. The particles had geometric diameters of about 1, 5, 10,
      and 15 microm. The tracheobronchial models, consisting of a trachea and two or
      more additional generations, had dimensions representative of a typical adult, a
      7-y-old child, and a 4-y-old child; the child-size models were appropriately
      scaled-down replicas of the adult-size model. Each deposition experiment was
      conducted using a steady inspiratory airflow representative of low physical
      activity for the appropriate age of individual: 20 L min(-1) for the adult; 9 L
      min(-1) for the 7-y-old; 5.5 L min(-1) for the 4-y-old. The results indicate that
      deposition efficiency of the particles increased substantially (up to 35 times)
      in all three models as particle diameter increased from 1-15 microm, undoubtedly
      as a result of particle impaction and sedimentation-related phenomena. An
      analysis of variance demonstrated the occurrence of statistically-significant (p
      < 0.05) main effects of hollow model size and particle size; the interaction
      between the two parameters was also significant. In general, deposition
      efficiencies of the various sizes of particles were greater in the child-size
      models than in the adult-size model; this effect may have risk assessment
      implications. In addition, the results obtained experimentally agreed more
      closely with those predicted using a radiation-protection mathematical particle
      deposition formulation as the particle size increased for each of the sizes of
      models.

PMID- 9169925
TI  - Skin dose from radionuclide contamination on clothing.
AB  - Skin dose due to radionuclide contamination on clothing is calculated by Monte
      Carlo simulation of electron and photon radiation transport. Contamination due to
      a hot particle on some selected clothing geometries of cotton garment is
      simulated. The effect of backscattering in the surrounding air is taken into
      account. For each combination of source-clothing geometry, the dose distribution
      function in the skin, including the dose at tissue depths of 7 mg cm(-2) and
      1,000 mg cm(-2), is calculated by simulating monoenergetic photon and electron
      sources. Skin dose due to contamination by a radionuclide is then determined by
      proper weighting of the monoenergetic dose distribution functions. The results
      are compared with the VARSKIN point-kernel code for some radionuclides,
      indicating that the latter code tends to underestimate the dose for gamma and
      high energy beta sources while it overestimates skin dose for low energy beta
      sources.

PMID- 9169926
TI  - Phantom-derived estimation of effective dose equivalent from X rays with and
      without a lead apron.
AB  - Organ dose equivalents were measured in a humanoid phantom in order to estimate
      effective dose equivalent (H(E)) and effective dose (E) from low-energy x rays
      and in the presence or absence of a protective lead apron. Plane-parallel
      irradiation conditions were approximated using direct x-ray beams of 76 and 104
      kVp and resulting dosimetry data was adjusted to model exposures conditions in
      fluoroscopy settings. Values of H(E) and E estimated under-shielded conditions
      were compared to the results of several recent studies that used combinations of
      measured and calculated dosimetry to model exposures to radiologists. While the
      estimates of H(E) and E without the lead apron were within 0.2 to 20% of expected
      values, estimates based on personal monitors worn at the (phantom) waist
      (underneath the apron) underestimated either H(E) or E while monitors placed at
      the neck (above the apron) significantly overestimated both quantities. Also, the
      experimentally determined H(E) and E were 1.4 to 3.3 times greater than might be
      estimated using recently reported "two-monitor" algorithms for the estimation of
      effective dose quantities. The results suggest that accurate estimation of either
      H(E) or E from personal monitors under conditions of partial body exposures
      remains problematic and is likely to require the use of multiple monitors.

PMID- 9169928
TI  - Adaptation of ECOSYS-87 to Hong Kong environmental conditions.
AB  - This paper describes the adaptation work carried out on the radioecological model
      ECOSYS for radionuclide transfer in the Hong Kong ecological environment. The
      adapted model predicts that the ingestion dose due to dry deposition in Hong Kong
      shows less pronounced seasonal dependence than that in Germany. This is mainly
      attributed to differences in climate, agricultural and farming practices adopted
      in the two places. Brief discussions on model sensitivity, uncertainty, and
      validation are also given.

PMID- 9169927
TI  - 152Eu depth profiles in granite and concrete cores exposed to the Hiroshima
      atomic bomb.
AB  - Two granite and two concrete core samples were obtained within 500 m from the
      hypocenter of the Hiroshima atomic bomb, and the depth profile of 152Eu was
      measured to evaluate the incident neutron spectrum. The granite cores were
      obtained from a pillar of the Motoyasu Bridge located 101 m from the hypocenter
      and from a granite rock in the Shirakami Shrine (379 m); the concrete cores were
      obtained from a gate in the Gokoku Shrine (398 m) and from a pillar top of the
      Hiroshima bank (250 m). The profiles of the specific activities of the cores were
      measured to a depth of 40 cm from the surface using low background germanium (Ge)
      spectrometers. According to the measured depth profiles, relaxation lengths of
      incident neutrons were derived as 13.6 cm for Motoyasu Bridge pillar (granite),
      12.2 cm for Shirakami Shrine core (granite), and 9.6 cm for concrete cores of
      Gokoku Shrine and Hiroshima Bank. In addition, a comparison of the granite cores
      in Hiroshima showed good agreement with Nagasaki data. Present results indicates
      that the depth profile of 152Eu reflects incident neutrons not so high but in the
      epithermal region.

PMID- 9169929
TI  - New agents for in vivo chelation of uranium(VI): efficacy and toxicity in mice of
      multidentate catecholate and hydroxypyridinonate ligands.
AB  - Soluble uranyl ion [UO2(2+), U(VI)] is a kidney poison. Uranyl ion accumulates in
      bone, and the high specific activity uranium isotopes induce bone cancer.
      Although sought since the 1940's, no multidentate ligand was identified, until
      now, that efficiently and stably binds U(VI) at physiological pH, promotes its
      excretion, and reduces deposits in kidneys and bone. Ten multidentate ligands
      patterned after natural siderophores and composed of sulfocatechol [CAM(S)],
      carboxy-catechol [CAM(C)], or hydroxypyridinone [Me-3,2-HOPO] metal-binding units
      have been tested for in vivo chelation of U(VI). Ligands were injected
      intraperitoneally (i.p.) into mice 3 min after intravenous (i.v.) injection of
      233U or (232+235)U as UO2Cl2 [ligand-to-metal molar ratio 75 to 92]. Regardless
      of backbone structure, denticity, or binding unit, all 10 ligands significantly
      reduced kidney U(VI) compared with controls or with mice given CaNa3-DTPA, and
      four CAM(S) or CAM(C) ligands also significantly reduced skeleton U(VI). Several
      ligands removed U(VI) from kidneys, when injected at 1 or 24 h. Injected at molar
      ratios > or = 300, 5-LIO(Me-3,2-HOPO) and TREN-(Me-3,2-HOPO) reduced kidney U(VI)
      to about 10% of control. Given orally to fasted mice at molar ratios > or = 300,
      those ligands significantly reduced kidney U(VI). In mice injected i.v. with 0.42
      micromol kg(-1) of 235U and given 100 micromol kg(-1) of one of those Me-3,2-HOPO
      ligands i.p. daily for 10 d starting at 1 h after the U(VI)) loss of kidney U(VI)
      was greatly accelerated, and the kidneys of treated mice showed no microscopic
      evidence of renal injury. Crystals of uranyl chelates with linear tetradentate
      ligands containing bidentate Me-3,2-HOPO groups demonstrate a 1:1 structure.
      Considering low toxicity, effectiveness, and reasonable cost, the structurally
      simple linear tetradentate ligands based on the 5-LI backbone (diaminopentane)
      offer the most promising approach to a clinically acceptable therapeutic agent
      for U(VI). Work is in progress to identify the most suitable CAM or HOPO binding
      unit(s).

PMID- 9169930
TI  - Towards a generalized model for the primary and secondary contamination of lakes
      by Chernobyl-derived radiocesium.
AB  - As part of the UK Ministry of Agriculture Fisheries and Food Directorate of
      Fisheries Research (MAFF/DFR) post-Chernobyl monitoring program, a detailed study
      was carried out of the change over time in dissolved-phase 137Cs concentrations
      in a number of lakes in Cumbria, UK. These measurements have been combined with
      published data on 137Cs in Cumbrian and other European lakes in order to develop
      and test a "double exponential" model for changes in lakewater concentrations: A
      exp(-k1t) + B exp(-k2t) where the exponential terms correspond, respectively, to
      the initial fast flush of activity through the system followed by longer-term
      transfers (timescale, years) from the catchment. Parameter values have been
      determined for this model by curve-fitting to the set of measurements of post
      Chernobyl 137Cs activities in lakes. Values of fitted parameters are shown to be
      related, in a simple manner, to the physical characteristics of the system, in
      particular water residence time and mean lake depth. These parameters are
      generalized to give a simple empirical model for the full set of study lakes. The
      model is shown to give estimates of 137Cs activity to within a factor of 5 of
      field data for a period of several years after the fallout. Initial fractional
      losses of activity from catchment to lake were determined to be within the range
      0.44-8.7% per year, declining exponentially with a mean rate constant 0.98 x 10(
      3) d(-1).

PMID- 9169931
TI  - Predictions and maps of county mean indoor radon concentrations in the mid
      Atlantic states.
AB  - Measured surface radium content, geologic province information, information on
      the fraction of homes with basements and with living-area basements, and
      measurements from the EPA/State Residential Radon Surveys, were used in a
      Bayesian mixed effects regression to predict the distributions of short-term
      winter and annual living-area average radon concentrations by county in the mid
      Atlantic states. The information provided by those explanatory variables is
      roughly equivalent to collecting an extra 12 observations per county, effectively
      doubling the amount of information in a typical county. Predicted county
      geometric means are subject to standard errors of 15% to 30% for typical
      counties, with the uncertainty in a given county depending on the number of radon
      measurements in the county and the amount of information about the geologic
      province that contains the county. After controlling for soil radium
      concentration and the effect of measuring in a basement vs. the first floor,
      typical geologic provinces are found to be associated with elevation or
      depression of indoor radon concentrations by 30% on average, with some provinces
      having effects of considerably larger magnitude.

PMID- 9169932
TI  - Radon in residences: influences of geological and housing characteristics.
AB  - 222Rn is a radioactive gas emitted during the decay of 238U. 222Rn is a
      recognized lung carcinogen in humans and a common indoor air contaminant. This
      paper describes the results of research undertaken in 894 residences of the
      Province of Quebec (Canada), in which one of the objectives was to evaluate the
      influence of geological and housing characteristics on 222Rn levels. After a
      random selection of homes, 222Rn concentrations were measured with alpha track
      detectors in the basement and the main bedroom during two consecutive 6-mo
      periods. Geological subsoil characteristics were determined from various sources
      (e.g., geological maps, databanks on uranium sampling in lake and stream
      sediments), and housing characteristics were documented with a questionnaire.
      Statistical variance analysis of data indicates that geological factors only
      explain 5% and 4.5% of the variations in 222Rn concentrations, respectively, in
      the basement and on the first floor. When variables relative to housing
      characteristics are added, the analysis explains only 18% and 15% of the
      variations in 222Rn concentrations in the basement and on the first floor. These
      results illustrate the difficulties in predicting 222Rn concentrations in homes.

PMID- 9169933
TI  - The variations in long term TLD measurements of environmental background
      radiation at locations in southeastern New York state and northern New Jersey.
AB  - The variations of the measured dose rate in air should be recognized especially
      where background radiation is used as a comparative benchmark to assess radiation
      surveillance and environmental remediation work. In this note, the natural
      variations of the combined gamma and cosmic-ray background air-dose rate as
      measured by lithium fluoride thermoluminescence dosimeters are reported. The
      dosimeters were deployed monthly at locations within 150 km of the Environmental
      Measurements Laboratory in New York City. Urban and suburban stations were
      established with simultaneous indoor and outdoor measurements at some locations.
      Measurements were obtained over 10 to 18 years. The mean air-dose rates from the
      six outdoor and four indoor stations vary from 50.8 to 123.1 nGy h(-1). The range
      of the annual dose rates expressed as a percent-difference of the minimum and
      maximum is 5.3 to 18.0%. Commonly, 1-mo deviations from the long term mean of
      about +/-10 to +/-25% are observed. An abrupt decrease in the annual dose rate at
      one of the measurement sites was attributed to a minor relocation of a dosimeter.
      Structural shielding factors for the first and second floors of a residence are
      reported. The ground level location of a dosimeter inside another residence
      apparently resulted in a very high shielding factor. Finally, a gradual decrease
      of the dose rate at most of the stations is shown to exist (approximately -0.3
      nGy h(-1) y(-1) for the outdoor stations). Plausible causes of this trend are
      briefly discussed.

PMID- 9169934
TI  - In-situ measurements of 137Cs in soil by unfolding method.
AB  - An improved in-situ spectrometry measurement of 137Cs concentration in soil is
      introduced. The method uses the information contained in the pulse spectrum in
      order to forego the need for soil sampling. The approach is based on the
      unfolding of responses of a collimated and uncollimated HPGe detector to primary
      0.662 MeV photons and to photons scattered forward in the soil. The calibration
      of the in situ equipment has been performed by Monte Carlo calculations and by
      experiments. For unfolding of experimental detector responses the code SAND II
      has been found reliable and capable of calculating distribution of 137Cs in soil
      profile with adequate accuracy for environmental monitoring purposes. The
      analysis of the spectra indicates that 137Cs concentration in soil 10 y after
      Chernobyl accident would be measurable using a middle HPGe detector (20-30%
      relative efficiency) and a counting time on the order of 1 h. Even with smaller
      detectors, 137Cs concentrations of 5 kBq m(-2) are measurable, and the depth
      distribution of 137Cs activities above 10 kBq m(-2) in the soil can be estimated
      by the presented method when a counting time on the order of 3 h is used.

PMID- 9169935
TI  - Photon dose equivalent rate from a cylindrical source using a point kernel
      technique.
AB  - The photon dose equivalent rate as a function of distance from a cylindrical
      source was calculated using a point kernel technique in the energy range 0.3-5
      MeV. Buildup factors for a single medium were those given by the geometric
      progression formula. The buildup factor for the whole geometry was considered as
      that from a multilayer shield represented by the Broder formula with two
      corrections applied to it: the first for finite shield and the second for the
      contribution of the last layer as given by Kitazume. The accuracy of this
      algorithm was tested by performing a MCNP (General Purpose Monte Carlo Code for
      Neutral Particle Transport) calculation for the same source and comparing the two
      sets of results. The conclusion is that the point kernel technique, with the
      corrections mentioned above included, gives results that agree with those
      obtained by using MCNP in most cases to within 10%. Therefore, the method
      presented here is adequate for performing a dose equivalent rate computation as
      the effort for using it is much smaller than that needed using the MCNP code.

PMID- 9169936
TI  - Response to Suchanek et al.

PMID- 9169937
TI  - More on nuclear waste dumping in the ocean.

PMID- 9169938
TI  - NTS fallout-induced cancer in southwestern Utah.

PMID- 9169939
TI  - Excessive liver oxidant stress causes mortality in response to burn injury
      combined with endotoxin and is prevented with antioxidants.
AB  - We studied the effect of the oral administration of a water-soluble antioxidant
      solution containing ascorbic acid, glutathione, and a precursor for glutathione
      synthesis, N-Acetyl-L-cysteine, on liver antioxidant activity, liver cell
      energetics, and mortality in rats in response to a 20% third-degree burn injury
      challenged 5 days later with an intraperitoneal injection of 30 mg/kg endotoxin.
      Rats with burns were fluid-resuscitated with subcutaneous Ringer's lactate
      solution according to the Parkland formula (4 cc/kg/%burn). Rats challenged with
      endotoxin 5 days after burn were given an additional 100 ml/kg of subcutaneous
      Ringer's lactate solution immediately after the injection of endotoxin. A group
      of rats with burns challenged with endotoxin 5 days after burn were given an oral
      antioxidant solution beginning after burn injury. Liver cell energetics were
      measured as tissue energy charge potential (ECP), adenosine triphosphate (ATP)
      content, and total adenine nucleotides. The levels of endogenous liver
      glutathione, catalase, vitamin C, and vitamin E were measured to monitor
      antioxidant status. We found that burn injury alone did not produce any mortality
      over the 6-day period despite a 35% decrease in liver energy charge potential
      resulting from a decrease in ATP, a 34% decrease in liver catalase activity, and
      a 20% decrease in liver vitamin C. It was interesting that glutathione increased
      and vitamin E remained unchanged. We found that endotoxin injury combined with
      burn injury produced a 61% mortality rate with a 63% decrease in liver energy
      charge potential, again resulting from a decrease in ATP, a 74% decrease in liver
      catalase activity, a 16% decrease in vitamin C, and a 29% decrease in vitamin E.
      Glutathione was significantly decreased compared with burn alone. We compared the
      liver antioxidant status of survivors with that of nonsurvivors who were killed
      when appearing moribund and found that glutathione was decreased by 51% and
      vitamin C by 73% in nonsurvivors over that in survivors, whereas catalase and
      vitamin E levels were comparable between the two groups. The oral administration
      of the antioxidants prevented mortality and the decrease in antioxidant activity
      and attenuated the decrease in energy charge potential. We conclude that a 20%
      burn produces a modest decrease in liver energy charge potential and antioxidant
      defenses without producing mortality. The addition of endotoxin further decreases
      liver antioxidant defenses, liver energy charge potential, and markedly increases
      mortality. Antioxidants, given post-burn, restored antioxidant defenses,
      attenuated the altered cell energetics, and prevented mortality, indicating
      oxidants to be the cause of mortality. This data also suggests that a critical
      value of decreases in antioxidant defenses and ATP exists, resulting in
      mortality.

PMID- 9169941
TI  - Pressure-controlled ventilation for the long-range aeromedical transport of
      patients with burns.
AB  - Pressure-controlled ventilation is used to treat smoke inhalation injury to
      achieve adequate oxygenation and ventilation at lower peak inspiratory pressures.
      A portable pressure-controlled time-cycled transport ventilator permits this
      modality to be used in the field. We have examined the safety and efficacy of
      this ventilator for aeromedical transfer of thermally injured patients. Burn
      flight teams transported 146 intubated patients with thermal injury to the U.S.
      Army Burn Center with this system. The average extent of burn injury was 40.45%
      total body surface area with an average full-thickness injury of 25.29% total
      body surface area. The transport ventilator was used for 57 rotary wing and 89
      fixed wing missions. The study group was transported a total of 86,889 miles
      without in-flight morbidity, mortality, or failure of ventilation. Arterial blood
      gas analysis at conclusion of flight demonstrated an arterial pH > or = 7.35 in
      85% of the patients, an arterial partial pressure of carbon dioxide < or = 45
      torr in 97%, and an arterial partial pressure of oxygen > or = 70 torr in 99%.
      Pressure-controlled ventilation performed by an experienced transport team with
      this ventilator is safe and effective for the long-range aeromedical transfer of
      intubated patients with burns.

PMID- 9169940
TI  - NMR relaxation studies on hepatic intracellular and extracellular sodium in rats
      with burn injury.
AB  - In vivo longitudinal (T1) and transverse (T2) relaxation times of hepatic
      intracellular and extracellular sodium were studied in rats with sham burn or
      burn injury with 23Na NMR spectroscopy and shift reagent. Burn injury decreases
      hepatic extracellular sodium content by 17% compared with sham burn, whereas it
      increases the percent of the fast T2 component of extracellular sodium,
      suggesting an increase in the fraction of bound Na+/- sites in the extracellular
      space. It is interesting that the relaxation characteristics of intracellular
      sodium remained unchanged despite a 57% increase in intracellular sodium content,
      suggesting the increase in intracellular free sodium is matched by either a
      proportional increase in intracellular bound sodium or an uncovering of ordered
      domain sites that can preferentially orient rapidly exchanging sodium ions. This
      study also demonstrated that spin lattice (T1) relaxation rates or the percent
      contribution of the fast/slow T2 components of the combined
      intracellular/extracellular 23Na signal (before the infusion of shift reagent)
      may also be sensitive to changes in intracellular sodium levels during pathologic
      changes.

PMID- 9169942
TI  - Effects of a rapidly scanned carbon dioxide laser on porcine dermis.
AB  - This study systematically examined the effect of varying continuous-wave carbon
      dioxide laser scanning parameters on the resultant tissue effects. The effects of
      varying scanning speed, laser power, and laser beam diameter were assessed.
      Residual thermal damage at the center of the crater was approximately 120 microm
      independent of dwell time and laser irradiance. However, thermal damage zones
      along the sides of the ablation crater increased as laser dwell times exceeded 50
      msec. This study demonstrates that under appropriate conditions a scanned
      continuous-wave carbon dioxide laser can ablate tissue with a zone of residual
      thermal injury less than 200 microm, making it useful for cutaneous surgery and
      the debridement of burn wounds before skin grafting is performed.

PMID- 9169943
TI  - Kinetics of soluble interleukin-2 receptor after mechanical and burn trauma.
AB  - Extended trauma causes a failure of T-lymphocyte function due to suppressed
      interleukin-2 synthesis; however, the role of IL-2 receptor, especially its
      soluble form (sIL-2R), needs to be further evaluated. It was the objective of the
      study to assess the kinetics of sIL-2R within different settings of trauma and to
      define its clinical value and possible predictive role. Three groups of patients
      with trauma were included in the study. Groups 1 and 2 consisted of multiply
      injured patients (injury severity score 35 +/- 4 and 32 +/- 4, respectively);
      burned patients formed group 3 (injury severity score 38 +/- 9). Serum samples
      were collected at the site of the accident (group 1) and during the posttrauma
      course in the hospital (group 2, daily; group 3, weekly) and sIL-2R was measured
      in these samples. sIL-2R was within the normal range in groups 1 and 2, but was
      significantly increased in group 3. There was no correlation between serum
      concentrations of this mediator and susceptibility to infectious complications or
      outcome.

PMID- 9169944
TI  - A hyaluronic acid membrane delivery system for cultured keratinocytes: clinical
      "take" rates in the porcine kerato-dermal model.
AB  - The clinical take rates of cultured keratinocyte autografts are poor on a full
      thickness wound unless a dermal bed is provided. Even under these circumstances
      two important problems are the time delay in growing autografts and the fragility
      of the grafts. A laser-perforated hyaluronic acid membrane delivery system allows
      grafting at early confluence without requiring dispase digestion to release
      grafts from their culture dishes. We designed this study to investigate the
      influence of this membrane on clinical take rates in an established porcine
      kerato-dermal grafting model. The study demonstrated a significant reduction in
      take as a result of halving the keratinocyte seeding density onto the membrane.
      The take rates, however, of grafts grown on the membrane at half or full
      conventional seeding density and transplanted to a dermal wound bed were
      comparable, if not better, than those of keratinocyte sheet grafts.

PMID- 9169945
TI  - Prolonged use of propranolol safely decreases cardiac work in burned children.
AB  - Propranolol has been shown to be effective for as long as 5 days in massively
      burned children to reduce heart rate and cardiac work. This article describes the
      use of propranolol given for 10 days to burned children to test whether the drug
      remains effective and safe in reducing heart rate and cardiac work for longer
      periods. We prospectively studied 22 children, 1 to 10 years of age with burns
      covering > or = 40% of their total body surface area. These children were treated
      with 0.5 to 1.0 mg/kg propranolol given orally or intravenously every 8 hours for
      10 days. In both septic and nonseptic patients, propranolol significantly
      decreased their daily average heart rate (between 10% and 13%, p < 0.05) and rate
      pressure product (between 10% and 16%, p < 0.05) compared with their 24-hour mean
      before propranolol treatment. No significant change in mean arterial blood
      pressure, or plasma urea nitrogen creatinine or glucose levels could be shown. No
      hypotension, hypothermia, azotemia, hyperglycemia or hypoglycemia, arrhythmia,
      bronchospasm, or peripheral ischemia was noted during or after treatment. Whereas
      propranolol lowered heart rate more per milligram per kilogram body weight when
      given intravenously, both routes were safe and effective. From these data, we
      conclude that propranolol can be given to decrease the work of the heart safely
      and effectively for > or = 10 days.

PMID- 9169946
TI  - Immunogenicity of glycerol-preserved human cadaver skin in vitro.
AB  - Donor allograft skin preserved in 85% glycerol is used as a temporary coverage
      for large burn wounds. Glycerol treatment does not affect the structural
      integrity of the skin; cells are well preserved but dead. However, cells
      expressing major histocompatibility class II molecules can still be observed. In
      this study we investigated the mechanism underlying the clinical observation that
      glycerol-treated alloskin will be destroyed but after a prolonged period. We
      compared the in vitro immunogenicity of untreated and 85% glycerol-treated human
      skin cells. Human purified blood T cells did not proliferate when cultured with
      allogeneic treated skin cells, whereas untreated cells induced a distinct
      response. A moderate response was measured after adding T cells and viable
      antigen presenting cells, such as monocytes, to the allogeneic treated skin
      cells. However, the response on untreated skin cells was much higher. These
      results favor the suggestion that after transplantation of glycerol preserved
      skin is performed, an inflammatory process mediated by infiltrating host
      monocytes occurs rather than a rejection process mediated by T cells.

PMID- 9169947
TI  - Facial mutilation after an assault with chemicals: 15 cases and literature
      review.
AB  - Facial mutilation after an assault with chemicals is rarely discussed in the
      literature even though it is a devastating injury that occurs worldwide and is
      not prohibited or punished by special laws. It is our purpose to describe the
      devastating outcome of facial mutilation after an assault with chemicals and to
      draw attention to this injury as a worldwide problem. We studied fifteen patients
      who sustained facial mutilation with chemicals. The common story was that the
      patient's spouse was the perpetrator, that sulfuric acid was used, and that the
      deed occurred after marital or financial discord. All victims were disfigured
      severely and most became reclusive and rarely left their homes. Six patients
      (40%) had total bilateral blindness and one suffered partial loss of vision.
      Lower eyelid ectropion (14), microstomia (12), cervical flexion contracture (10),
      ear deformity (8), and nostril stenosis (6) were common. Few of the perpetrators
      were prosecuted. We reviewed the literature and found that the problem has been
      described all over the world, and that the outcome is similar to that which we
      described. The problem deserves worldwide recognition and attention.

PMID- 9169948
TI  - The management of burns under conditions of limited resources using topical
      aqueous sulfamylon (mafenide) hydrochloride spray.
AB  - The burn unit establishment in a Vietnamese military hospital (1970 to 1971) is
      an example of the management of burns under conditions of limited resources. The
      problems encountered and methods used in their solution are still relevant. This
      is the first (and possibly still the only) instance of such clinical use of
      topical Sulfamylon (mafenide) aqueous spray as the sole pregraft antibacterial
      agent for patients with deep partial-thickness and full-thickness burns (and
      associated injuries). The mafenide spray open treatment resulted in a
      bacteriostatic film permitting eschars to remain uninfected while more
      superficial burns healed and general status improved, enabling delayed grafting
      to be effective. Use of operating rooms, supplies, and personnel was minimized.
      The study group contained 211 patients; 86 (approximately 40%) had burns that
      exceeded 20% body surface area, and 26 (approximately 12%) had burns that
      exceeded 40% body surface area. As the procedures became fully established, all
      of the last 110 patients of this series survived. Only 17 deaths occurred in the
      total series; none were attributed to infection.

PMID- 9169949
TI  - Dupuytren's contracture after burns of the upper extremity.
AB  - A case of Dupuytren's contracture in a patient with previous history of burns of
      the upper extremity is reported. Because this patient has no predisposition to
      the disease, burns of the upper extremity should be considered as a trigger to
      the onset of the disease.

PMID- 9169951
TI  - To splint or not to splint--past philosophy and present practice: part III.

PMID- 9169950
TI  - Do custom-fitted pressure garments provide adequate pressure?
AB  - Pressure garment therapy has become the worldwide standard of care for the
      prevention and treatment of hypertrophic scars. There are many reports in the
      literature on pressure garment therapy but few studies state the amount of
      pressure actually provided. The purpose of our study was to determine the amount
      of pressure applied to the scar/garment interface by custom-fitted pressure
      garments. The Iscan (Tekscan, Inc.) system was used to document scar/garment
      interface pressures of 144 new custom-fitted pressure garments. Average pressure
      readings for garments for the anterior thigh, anterior trunk, abdomen, buttocks,
      posterior trunk, posterior thigh, and arm were less than 22 mm Hg. Average
      pressure readings for the dorsal hand, leg, forearm, and dorsal foot were more
      than 28 mm Hg, with smaller relative standard deviations. The pressure readings
      varied greatly between garments in this group, frequently resulting in standard
      deviations that were higher than the pressure readings. The data show that
      despite precise fitting techniques, pressure garments do not provide a consistent
      amount of pressure at the scar/garment interface. This means that studies that
      report results of pressure therapy, but do not verify the amount of pressure
      applied, are of limited value. Precise determination of pressure "dose" must be
      made before the efficacy of pressure garment therapy can be determined
      objectively.

PMID- 9169952
TI  - Determining when care for burns is futile.
AB  - Age, burn size, inhalation injury, and comorbid diseases are important factors in
      predicting survival of patients with burn injuries. These same factors are
      important in attempting to objectively define the point when burn care is futile.
      We reviewed the records of 3301 patients admitted to our Burn Center between
      January 1, 1986, and December 31, 1994. There were 114 deaths (3.45%), of which
      44 occurred within the first few days of admission. Seventy patients died at a
      later date. A do-not-resuscitate with comfort-measures-only order was written on
      33 patients (26.7%). We have developed objective criteria that include age,
      extent of burn, presence of inhalation injury, and major organ dysfunction to be
      applied in the determination of futility of further therapy, either at the time
      of admission or when patients develop progressive multi-organ system failure
      during the hospital course.

PMID- 9169953
TI  - Carotenoids and antioxidant vitamins in patients after burn injury.
AB  - Oxidative stress may contribute to secondary tissue damage and impaired immune
      function in patients after burn injury. The purpose of our study was to describe
      plasma antioxidant micronutrient concentrations in 26 adult patients admitted
      with extensive burn injuries (> 20 % total burn surface area) to a level-1 trauma
      burn center during a 21-day period after admission. The effect of administering
      beta-carotene was also examined with use of a prospective randomized subjects
      design: patients received either placebo or 30 mg/day in an enteral feeding.
      Plasma concentrations of alpha- and gamma-tocopherol, carotenoids (alpha and beta
      carotene, lycopene, beta-cryptoxanthin, lutein), and retinol were measured with
      high- performance liquid chromatography, and vitamin C was quantified with
      spectrophotometry, at baseline and twice per week. Vitamin C, tocopherol, and
      retinol concentrations were low at baseline, but levels increased significantly
      over the study period in both groups (p < 0.05). Plasma beta-carotene
      concentration increased when this carotenoid was provided in the oral feeding.
      Otherwise, plasma carotenoid concentrations were low at baseline and remained low
      throughout the study period despite normalization of associated lipids.

PMID- 9169954
TI  - Iron burns to the hand in the young pediatric patient: a problem in prevention.
AB  - Iron burns to the hand may result in both functional and cosmetic deformities in
      the young pediatric patient. To gain a better understanding of these injuries in
      terms of demographics, treatment, and outcome, and to address possible measures
      for prevention, the medical records of 82 pediatric patients suffering iron burns
      to the hand during the period 1987 to 1993 were reviewed. Iron burns to the hand
      occurred most commonly in male children less than 2 years of age. Most were minor
      partial-thickness burns that were treated in the outpatient setting with no
      adverse sequelae. Fifteen percent of patients, however, sustained full-thickness
      burns that required grafting. Ten percent of patients developed complications
      including hypertrophic scarring and scar contractures requiring surgical release.
      Socioeconomic factors and parental inexperience appeared to play a significant
      role, as most of these injuries occurred in low-income, single-parent, single
      child households. Most injuries were unintentional, however, many were caused by
      carelessness or neglect. Abuse was suspected or proven in 7% of cases. Parents
      may be unaware of the consequences of leaving a child unattended in the presence
      of a hot iron. The incidence of these injuries could be reduced effectively by
      improved public awareness of the problem and education in prevention.

PMID- 9169955
TI  - Chemical dependency in patients with burn injuries: a fortress of denial.
AB  - Chemical dependency is frequently encountered in patients admitted to burn
      centers. We were interested in the prevalence of chemical dependency among our
      patients, as well as the rate at which those patients sought further treatment
      after discharge. Blood and urine specimens were collected within 24 hours of
      admission from 843 patients more than 18 years of age admitted with acute
      injuries. Many patients admitted to substance abuse during routine psychosocial
      evaluation; others admitted only when confronted by the counselor with positive
      toxicology test results. Of 51 patients counseled, 12 denied a history of
      chemical dependency. Of the other 39, 21 admitted to a history of chemical
      dependency, and 31 tested positive for either alcohol or drugs in toxicology
      screening. Every patient identified with chemical dependency was informed of
      existing substance abuse programs and given the opportunity to be referred to any
      of these programs. Only half of the patients who were offered rehabilitation
      therapy accepted treatment.

PMID- 9169956
TI  - Choosing drug of choice from restrictive formulary.

PMID- 9169957
TI  - Channeling of three newly introduced antidepressants to patients not responding
      satisfactorily to previous treatment.
AB  - The demand for knowledge about differences in effectiveness, tolerability,
      safety, and economic outcomes between and within groups of antidepressant drugs
      when used in routine daily clinical practice is growing. For gaining this
      knowledge, observational pharmacoepidemiologic studies are often the most
      feasible option. However, the results of such studies can only be valid if either
      patient baseline characteristics associated with the outcome under study are
      similar or if differences can be adjusted for in the analysis. The aim of this
      study was to evaluate to what extent and for what type of patients three
      antidepressant drugs recently introduced in The Netherlands (mirtazapine,
      sertraline, and venlafaxine) were prescribed during the first year after their
      introduction and whether there were differences compared with longer-available
      antidepressant drugs. For this purpose, prescription drugs histories from 20
      pharmacies serving a population of approximately 200,000 persons were analyzed.
      One year after their introduction, the newly introduced antidepressant t drugs
      accounted for approximately 6% of new uses of all antidepressant drugs. In
      comparison to longer-available antidepressant, the newly introduced
      antidepressant drugs were more often prescribed for patients with prior
      prescriptions of another antidepressant drug (rate ratio [RR] 2.7 [95% confidence
      interval [CI], 2.3-3.0]), for patients with prior prescriptions of other
      psychotropic medicines (RR 1.3 [95% CI, 1.1-1.4), and by psychiatrists (RR 1.9
      [95% CI, 1.6-2.2]). In addition, the newly introduced antidepressant drugs seemed
      to be more often, although not significantly, prescribed for patients who had
      been hospitalized on a psychiatric ward (RR 1.5 [95% CI, 0.9-2.5]). No
      differences were observed with regard to age and gender distribution, the total
      number of medicines prescribed, and prescriptions of any cardiovascular or
      gastrointestinal medicine. These finding suggest that a significant proportion of
      the patients receiving one of the newly introduced antidepressant drugs did not
      respond satisfactorily to previous pharmacologic treatment. This channeling
      phenomenon may have important consequences for the interpretation of
      observational comparisons between different antidepressant drugs after their
      introduction.

PMID- 9169958
TI  - Pulse-dosing and conventional application of doxepin: effects on psychopathology
      and hypothalamus-pituitary-adrenal (HPA) system.
AB  - It has been shown that a single pulse-dosing (PD) dose of clomipramine improves
      depressive symptoms. However, so far PD and conventional (CONV) application of
      antidepressants have never been directly compared for an extended period. We
      performed a double-blind study of PD and CONV application of doxepin (DOX) in
      depressed patients. After a 1-week placebo treatment, nine parents in the PD
      group received 250 mg of DOX every 6 days and placebo on the other days until day
      39. Ten patients in the CONV group received increasing dosages of DOX until day 7
      and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)
      suppression/corticotropin-releasing hormone (CRH)-stimulation tests were
      completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21.
      In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D)
      differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p <
      0.03). In the CONV group, however, HAM-D scores improved significantly after 2
      days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day
      39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between
      the HAM-D scores of the two groups. In the PD group, the decline of cortisol
      after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions
      (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV
      group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs.
      10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area
      under-the-curve cortisol response after CRH was attenuated in the PD group (5,667
      +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01,
      respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/-
      2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude
      that CONV application of DOX is clinically superior compared with PD and that
      both modes of application have attenuating effects on hypothalamus-pituitary
      adrenal system activity.

PMID- 9169960
TI  - Pharmacokinetics of oral triazolam in children.
AB  - The purpose of this study was to determine the pharmacokinetic behavior of
      triazolam in children. Nine healthy children, aged 6 to 9 years, received oral
      triazolam (0.025 mg/kg suspended in Kool-Aid, Kraft General Foods, Chicago, IL)
      before dental treatment. Plasma triazolam concentrations were measured by gas
      chromatography/mass spectrophotometry at approximately 5, 15, 30, 45, 60, 90,
      120, 180, and 240 minutes. A one-compartment model with first-order absorption
      and varying parameters was used, and estimated concentration curves were obtained
      for each subject. The observed peak plasma concentration was 8.5 +/- 3.0 ng/mL
      (mean +/- SD). The observed time to peak plasma concentration was 74 +/- 25
      minutes. Elimination half-life was 213 +/- 144 minutes. Substantial recovery from
      signs and symptoms of clinical sedation required 180 to 240 minutes. The long
      duration of effect and relatively slow elimination should be noted by clinicians
      concerned with patient safety.

PMID- 9169959
TI  - A multicenter, double-blind comparison of the effects of nefazodone and
      fluoxetine on sleep architecture and quality of sleep in depressed outpatients.
AB  - This study was an 8-week, randomized, double-blind, parallel-group investigation
      that compared the effects of nefazodone and fluoxetine on sleep architecture and
      on clinician- and patient-rated sleep measures in 43 outpatients with moderate to
      severe, nonpsychotic major depressive disorder and insomnia. Twenty-two patients
      received nefazodone 200 mg daily for 1 week, followed by 400 mg daily for 7
      weeks. Twenty-one patients received fluoxetine 20 mg daily. Dosage increases (to
      500 mg/day for nefazodone and 40 mg/day for fluoxetine) were available after day
      29, depending on clinician judgement. Sleep parameters were measured during
      baseline phase, while patients were unmeasured and symptomatic, and at weeks 2,
      4, and 8 of treatment. Nefazodone and fluoxetine were equally effective as
      antidepressants. However, compared with baseline, nefazodone increased sleep
      efficiency and reduced the number of awakenings and percent awake and movement
      time, whereas fluoxetine increased the number of awakenings and did not
      significantly alter sleep efficiency or percent awake and movement time. Although
      fluoxetine increased stage 1 sleep and rapid eye movement (REM) latency and
      reduced total percent REM sleep, nefazodone increased REM sleep, decreased REM
      latency, and did not alter stage 1 sleep. Differences between treatment groups,
      based on change from baseline, revealed greater sleep efficiency, fewer
      awakenings, less percent awake and movement time, less percent stage 1 and more
      REM sleep, and shorter REM latency for nefazodone compared with fluoxetine.
      Significantly greater improvement in clinician- and patient-rated sleep
      disturbance was found with nefazodone compared with fluoxetine. Nefazodone was
      associated with better sleep quality.

PMID- 9169961
TI  - Modification of 35% carbon dioxide hypersensitivity across one week of treatment
      with clomipramine and fluvoxamine: a double-blind, randomized, placebo-controlled
      study.
AB  - The effects of short treatments (7 days) with clomipramine and fluvoxamine on the
      reactivity to inhalations of 35% CO2/65% O2 were compared in 39 panic patients
      who had positive responses to 35% CO2 inhalations. A double-blind, randomized,
      placebo-controlled design was applied. Each patient was given the 35% CO2
      challenge on days 0 (before starting treatment), 3, and 7. Patients on placebo
      did not report any significant changes in their reactivity to 35% CO2 across the
      three sessions, whereas patients on clomipramine and fluvoxamine reported a
      significant attenuation of the reactivity on day 7. These results indicate that
      treatments with clomipramine and fluvoxamine decrease hypersensitivity to 35% CO2
      after a few days, suggesting a relevant role of the modulation of CO2 sensitivity
      by the serotonergic system in antipanic properties of these compounds.

PMID- 9169962
TI  - Lithium pharmacokinetics in Chinese manic-depressive patients.
AB  - The pharmacokinetics of lithium was studied in 16 manic-depressive Chinese adults
      who were on lithium therapy in Hong Kong. A two-compartment open model was used
      to describe the plasma data obtained. The steady-state volume of distribution and
      total plasma clearance were estimated to be 63.4 +/- 38.3 L and 1.47 +/- 0.49
      L/hr, respectively, which were similar to those reported in studies of Caucasian
      subjects. The lithium clearance was found to be significantly related to lean
      body mass (r = 0.646, p < 0.01) but not to either total body weight, age, or
      creatinine clearance. Interindividual variability in lithium clearance was
      substantially reduced to a coefficient of variation of 24.6% from 33.3% when lean
      body mass was considered. The combined plasma and urine data indicate that the
      rate and extent of lithium absorption were similar to those of earlier studies in
      Caucasian subjects on a standard lithium dosage.

PMID- 9169963
TI  - The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness.
AB  - Anticonvulsants are used extensively in the treatment of bipolar disorder.
      Treating depression in bipolar disorder can be difficult because of the limited
      antidepressant effects of the standard mood stabilizers and the tendency of
      antidepressants to induce mania or decrease cycle length. Lamotrigine is a new
      anticonvulsant with few side effects that may have mood-stabilizing and elevating
      effects. Its mechanism of action probably involves the inhibition of excessive
      release of excitatory amino acids such as glutamate. Antiglutamatergic agents may
      be antidepressant and mood stabilizing. A case series of 16 patients treated with
      lamotrigine (dose range 50 mg to 250 mg, mean dose of responders = 141 mg) is
      presented along with two case reports. All patients were considered treatment
      resistant bipolar type I or II. Patients were rated on average 5 weeks after
      starting lamotrigine using a semistructured follow-up form that included symptom
      rating, Clinical Global Impressions (CGI), and Global Assessment of Functioning
      (GAF) scores. Eight of 16 patients were rated as "responders" (CGI < or = 2) and
      had a mean increase of 16 in their GAF scores. Lamotrigine seems to have
      antidepressant and mood-stabilizing effects, but this requires confirmation in
      randomized, controlled trials.

PMID- 9169964
TI  - A treatment for tardive dyskinesia and some other extrapyramidal symptoms.
AB  - The effects of the administration of acetazolamide and thiamine (A + T) on the
      symptoms of tardive dyskinesia (TD) and parkinsonism of 8 elderly and 25 younger
      chronic hospitalized mental patients were examined in a placebo-controlled,
      double-blind, counterbalanced two-period cross-over study with initial baselines
      and intervening washout periods. All patients were maintained on their prestudy
      psychoactive and anti-Parkinson medications, without alteration, throughout the
      study. The elderly group received 1.5 g acetazolamide and thiamine per day in
      three divided doses for 3 weeks. The younger group received 1.5 g thiamine and
      2.0 g acetazolamide per day in divided doses for 2 months. Both groups showed a
      significant decrease in scores on the Abnormal Involuntary Movement Scale (TD)
      and the Simpson-Angus Neurological Rating Scale (parkinsonism) while on A + T.
      The A + T effects were unrelated to age, gender, diagnosis, or maintenance
      medications.

PMID- 9169965
TI  - Extrapyramidal symptoms in patients treated with risperidone.
AB  - Data on extrapyramidal symptoms (EPS) from both arms of the North American
      multicenter comparative study of risperidone, placebo, and haloperidol were
      analyzed. The subjects were 523 patients with chronic schizophrenia who, after a
      1-week washout period, received placebo, risperidone (2, 6, 10, or 16 mg/day), or
      haloperidol (20 mg/day) for 8 weeks; the trial was completed by 253 patients.
      Severity of EPS was assessed by means of the Extrapyramidal Symptom Rating Scale
      (ESRS). Mean changes (increases) in ESRS scores from baseline to worst score were
      significantly lower in each risperidone group than the haloperidol group on the
      total ESRS (parkinsonism + dystonia + dyskinesia), total parkinsonism,
      hypokinetic symptoms, and on the questionnaire (p < 0.001). On several of the
      subscales (dyskinesia, buccolinguomasticatory, and Clinical Global Impression
      severity of dyskinesia), mean change scores were significantly lower in some of
      the risperidone groups than in the placebo group (p < 0.05). At the clinically
      most effective risperidone dose (6 mg/day), the mean ESRS change score was not
      significantly different from that of the placebo group. A significant linear
      relationship was noted between mean change scores and increasing risperidone dose
      on 4 of the 12 ESRS subscales; nevertheless, even at 16 mg/day of risperidone,
      mean change scores were lower than in the haloperidol group. A linear
      relationship between increasing risperidone dose and use of antiparkinsonian
      medications was also apparent. Acute dystonic reactions occurred both in patients
      receiving risperidone and haloperidol. Patients with severe baseline EPS were at
      higher risk of EPS during the study than patients with low or moderate baseline
      EPS. It is concluded that low doses of risperidone cause few or no EPS and
      recommendations for initiation of risperidone treatment are made.

PMID- 9169966
TI  - A novel tool to quantify physical activities: ambulatory accelerometry in
      psychopharmacology.
AB  - Accelerometry by means of body-mounted piezoresistive sensors was evaluated as a
      new method to quantify physical activities (body posture and physical and
      locomotor activity) in relation to the sedative and cardiovascular effects of
      benzodiazepines, in an ambulatory study. In a double-blind, randomized, crossover
      study, 12 healthy men received either an oral dose of 2 mg lorazepam, 0.5 mg
      alprazolam, 1 mg alprazolam, or a placebo on 4 different days. By means of a
      portable digital recorder, each day 4 hours of continuous measurements of
      accelerometer signals and heart rate were performed in a living room in the
      hospital. Changes in subjective sleepiness were assessed at the beginning,
      halfway, and at the end of the recording period. A separate validation study of
      the ambulatory environment was performed in three subjects, in which computer
      classification of activities based on accelerometry was compared with visual
      evaluation of simultaneously recorded videotapes. In our validation study,
      comparison of the computer classification with visual analysis based on
      videotapes revealed an overall agreement for spontaneous and standardized
      activities of 88% and 96%, respectively. In our pharmacological study, the
      subjects spent more time in the lying position (p < 0.01) and less time in the
      sitting position (p < 0.01) after benzodiazepine administration; the effects were
      strongest for lorazepam. Motility during static activities was reduced (p <
      0.025), with motility after lorazepam administration being lowest. Both lorazepam
      and alprazolam (0.5 and 1 mg) increased subjective sleepiness (p < 0.01). On
      average , lorazepam induced an overall increase in mean heart rate of about 6%,
      whereas alprazolam reduced mean heart rate by 2% versus placebo (p < 0.01); the
      effects were not dependent on posture. The validation study showed that
      accelerometry forms a reliable method to quantify aspects of normal daily
      activities. Our pharmacological study revealed that quantification of body
      postures, physical activity, and motility by means of ambulatory accelerometry
      proves to be an objective and promising tool to evaluate the psychological and
      cardiovascular effects of (psycho) pharmaca in relation to the postural and
      mobility activities of normal daily life.

PMID- 9169967
TI  - Selective serotonin reuptake inhibitor-induced serotonin syndrome: review.
AB  - The selective pharmacology of the selective serotonin reuptake inhibitors (SSRIs)
      results in a lower potential for pharmacodynamic drug interactions relative to
      other antidepressants such as the tricyclic antidepressants (TCAs) and monoamine
      oxidase inhibitors (MAOIs). However, the SSRIs have been implicated in the
      development of the serotonin syndrome--a potentially life-threatening
      complication of treatment with psychotropic drugs. The syndrome is produced most
      often by the concurrent use of two or more drugs that enhance central nervous
      system serotonin activity and often goes unrecognized because of the varied and
      nonspecific nature of its clinical features. The serotonin syndrome is
      characterized by alterations in cognition (disorientation, confusion), behavior
      (agitation, restlessness), autonomic nervous system function (fever, shivering,
      diaphoresis, diarrhea), and neuromuscular (ataxia, hyperreflexia, myoclonus)
      activity. The difference between this syndrome and the occurrence of adverse
      effects caused by serotonin reuptake inhibitors alone is the clustering of the
      signs and symptoms, their severity, and their duration. There are important
      pharmacokinetic interactions between SSRIs and other serotonergic drugs due
      principally to their effects on the cytochrome P450(CYP) isoenzymes, the
      potential for which varies widely amongst the SSRI group, which may increase the
      likelihood of a pharmacodynamic interaction. The exceptionally long washout
      period required after fluoxetine discontinuation may cause additional problems
      and/or inconvenience. Patients with serotonin syndrome usually respond to
      discontinuation of drug therapy and supportive care alone, but they may also
      require treatment with antiserotonergic agent such as cyproheptadine,
      methysergide, and/or propranolol. To reduce the occurrence, morbidity, and
      mortality of the serotonin syndrome, it must be both prevented by prudent
      pharmacotherapy and given prompt recognition when it is present.

PMID- 9169968
TI  - Nefazodone- and/or sodium tetradecyl sulfate-associated leukopenia, fever, and
      shaking chills in a patient with premenstrual dysphoric disorder.

PMID- 9169969
TI  - Venlafaxine-induced hyponatremia.

PMID- 9169970
TI  - Pindolol augmentation of tranylcypromine in psychotic depression.

PMID- 9169971
TI  - The monoamine oxidase inhibitor (MAOI) diet and kosher pizza.

PMID- 9169972
TI  - Tyramine content in Chinese food.

PMID- 9169973
TI  - Management of breakthrough panic disorder symptoms during pregnancy.

PMID- 9169974
TI  - Phenobarbital-induced disinhibition in the developmentally disabled: case report.

PMID- 9169975
TI  - Clozapine-induced necrotizing colitis.

PMID- 9169976
TI  - Cellulitis, eosinophilia, and unilateral pleural effusion associated with
      clozapine treatment.

PMID- 9169977
TI  - Clozapine and neuroleptic malignant syndrome: a never-ending story.

PMID- 9169978
TI  - Effectiveness of herbal medicine (shakuyaku-kanzo-to) for neuroleptic-induced
      hyperprolactinemia.

PMID- 9169979
TI  - The nondichotomy between lethal catatonia and neuroleptic malignant syndrome.

PMID- 9169980
TI  - Untreated psychopathology of candidates to "normal volunteers".

PMID- 9169981
TI  - Abuse liability of flunitrazepam.
AB  - Flunitrazepam is among the most frequently prescribed hypnotics in many
      countries. Although it was never marketed in the United States, flunitrazepam, in
      recent years, has been smuggled into the country, and reports of abuse--including
      alleged use of the drug to facilitate "date rape"--have attracted a great deal of
      scrutiny. It has been suggested that flunitrazepam may have greater liability for
      abuse than other benzodiazepines; such suggestions are supported by surveys of
      opioid abusers, many of whom report a distinct preference for flunitrazepam over
      other benzodiazepines. Experimental studies of animals and normal human subjects
      indicate that, although flunitrazepam has high efficacy and is very potent, it is
      pharmacologically similar to most other benzodiazepines. Although the studies are
      limited in number and scope, the data show no apparent differences between
      flunitrazepam and other benzodiazepines in ability to produce drug-taking or drug
      seeking behavior, in capacity to produce physiologic dependence, nor in the
      characteristics of withdrawal after administration of an antagonist or
      discontinuation of treatment. Similar to other benzodiazepines, flunitrazepam
      produces dose-dependent effects on psychomotor performance and recall.
      Flunitrazepam does not seem to be involved in medical emergencies more often than
      other benzodiazepines, and there is no indication that flunitrazepam is more
      toxic than other benzodiazepines when taken in overdose by drug abusers or other
      individuals. Survey research among typical patient populations suggests that
      flunitrazepam is characteristic of benzodiazepines in that it is used
      appropriately and conservatively, with low liability for abuse. Thus the reported
      preference for flunitrazepam among opioid abusers seems to be the only way in
      which flunitrazepam is distinguished from other benzodiazepines; it is unclear
      what characteristics of the drug may be responsible for this reported preference.
      The evidence considered in this review indicates that abuse of flunitrazepam in
      this special population is not associated with any distinctive threats to the
      health of the general public.

PMID- 9169982
TI  - Development and characterization of a mini capsular extrusion system for enteric
      delivery of metronidazole bearing liposomes.
AB  - A capsular extrusion system was developed for enteric delivery of metronidazole
      loaded liposomes. The system is essentially based on a miniosmotic pump except
      that the extrusion in the present system is brought about by the swelling of a
      swellable polymer which raises the vestibule and extrudes out the contents
      through a deliver orifice. Drug reservoir of the system contained freeze dried
      liposomes which become hydrated prior to extrusion. Extruded liposomes were
      uniform in size with 45-68% incorporation of metronidazole. When tested for in
      vitro antiamoebic and antibacterial activity it was found that the effectiveness
      of liposomal metronidazole was significantly higher as compared to the
      unformulated drug.

PMID- 9169983
TI  - Application of a colon delivery capsule to 5-aminosalicylic acid and evaluation
      of the pharmacokinetic profile after oral administration to beagle dogs.
AB  - Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid
      (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and
      evaluated by an in vivo experiment using beagle dogs. As a reference drug,
      sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule
      preparation. After the oral administration of SASP at the does of 25.0 mg/kg, the
      mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was
      9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0
      mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first
      appearance of 5-ASA into the systemic circulation was almost the same value
      between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP
      capsule than from PCC. These results suggest that this 5-ASA preparation would be
      an useful dosage form for the therapy of IBD from the point of avoiding the side
      effect of sulfapyridine, one of the metabolites of SASP.

PMID- 9169984
TI  - Modeling the route of administration-based enhancement in the brain delivery of
      EAB 515, studied by microdialysis.
AB  - EAB 515 (S-alpha-amino-5-phosphonomethyl[1,1'biphenyl]-3-propanoic acid) is an
      extremely hydrophilic N-methyl-D-aspartate antagonist. It shows marked CNS
      activity, in that it is a potent neuroprotector in models of cerebral ischemia,
      and also demonstrates social and non-social behavioral alteration following
      systemic administration in animals. Because of its high degree of ionization at
      physiologic pH, one would not expect appreciable brain uptake of EAB 515 across
      tight junctions of the blood-brain barrier. This is in contrast to its
      pharmacologic effect as well as brain/plasma ratios measured during systemic
      administration in rats. These observations lead us to investigate other transport
      pathways that might account for its brain uptake. Such mechanistic information is
      imperative in rational drug delivery and drug design strategies. Upon
      intracerebroventricular administration, the observed steady-state cortical
      extracellular fluid concentrations of EAB 515 were over 100-fold higher than
      those observed following intravenous administration, when normalized for the
      dosing rate. This increased distribution into the brain, based upon the route of
      administration, suggests the transport of drug directly between the cerebrospinal
      fluid and the brain extracellular space. The parameters of the model that
      adequately describes the data obtained from the two routes of administration in
      individual animals were estimated. The clinical significance of these results is
      in the use of intracerebroventricular administration for enhanced brain delivery
      of hydrophilic drugs that poorly cross the blood-brain barrier.

PMID- 9169985
TI  - Pharmacokinetics of mitomycin C (MMC) after intraperitoneal administration of MMC
      gelatin gel and its anti-tumor effects against sarcoma-180 bearing mice.
AB  - Gelatin viscous solution containing mitomycin C (MMC) was prepared and its
      antitumor effects were evaluated toward sarcoma-180 (S-180) ascite tumor bearing
      mice. Among various gelatin concentrations, 3% and 5% gelatin solutions
      potentiated the antitumor effects of MMC (7.5 mg/kg) against S-180 bearing mice.
      A "bell-shaped" profile was observed between % release of MMC from the gelatin
      matrix and increased life span (ILS) %. On the other hand, in the case of 10
      mg/kg dose of MMC, 7.5% and 10% gelatin solutions potentiated its antitumor
      effects. At both doses of 7.5 and 10 mg/kg of MMC, decrease in body weight of
      mice after intraperitoneal administration of MMC were suppressed by increasing
      the concentration of gelatin. To confirm a possible mechanism for increase in ILS
      % after intraperitoneal (i.p.) administration of the gelatin viscous solution
      containing MMC, we examined the pharmacokinetics of MMC after i.p. administration
      into rats. By the use of 3 % gelatin solution, mean residence time (MRT) and Tmax
      values were significantly prolonged, and Cmax was decreased as compared with the
      administration of MMC solution. These results suggested that the enhancement of
      antitumor effect of MMC by the gelatin viscous solution could be caused by
      decrease in the clearance rate of MMC from the peritoneal cavity to systemic
      circulation due to decreasing its diffusivity in gelatin matrix.

PMID- 9169986
TI  - Comparative evaluation of the severity of gastric ulceration by solid dispersions
      and coprecipitates of indomethacin.
AB  - The ulcerogenic activity of indomethacin was studied in rats following single and
      chronic doses of indomethacin in the form of pure drug, solid dispersions and
      coprecipitates. Each formulation was administrated as a suspension in a 2%
      methylcellulose solution. Gastrointestinal ulceration was assessed, four hours
      after a single dose and 24 hours following the last dose of a chronic four day
      dosing regimen, by counting the number of lesions and ulcers present. A rating
      scale was employed to evaluate the severity index. The coprecipitate formulation
      produced less severe ulceration than the solid dispersion and pure drug. This
      suggests that the severity of ulceration than the solid dispersion and pure drug.
      This suggests that the severity of ulceration may be related to the preparation
      methodology and drug release kinetics.

PMID- 9169987
TI  - Targeting naproxen to non-parenchymal liver cells protects against endotoxin
      induced liver damage.
AB  - Non-steroidal anti-inflammatory drugs (NSAID's) could be of value in the
      treatment of liver disease; however, their use in this situation is limited by
      renal side effects. Therefore, we explored whether naproxen covalently bound to
      human serum albumin NAP-HSA) was able to reduce toxicity in an acute model of
      liver disease induced by endotoxin in rats pretreated with Corynebacterium
      parvum. In the isolated perfused liver of such animals endotoxin induced
      cholestasis (0.62 +/- 0.05 vs. 0.24 +/- 0.09 microliter.min-1.g liver-1; p <
      0.05), increased vascular resistance (11300 +/- 400 vs. 311000 +/- 2000 dyn.s.cm
      5; p < 0.05) and alanine aminotransferase release (22 +/- 9 vs. 149 +/- IU/l; p <
      0.05). At the highest dose tested (22 mg/kg, corresponding to 6.0 mumoles
      naproxen), NAP-HSA normalized ALT release (21 +/- 10 IU/l: p < 0.05) while an
      equimolar amount of non-targeted naproxen was only partially effective (56 +/- 19
      IU/l). A conventional dose of naproxen similarly prevented transaminase release.
      Cholestasis and increased vascular resistance were also prevented by NAP-HSA.
      Drug targeting by linking drugs to proteins is a potentially useful approach to
      maximizing drug effect while minimizing adverse events; this could be
      particularly useful for compounds with potentially serious adverse effects in
      patients with chronic liver disease such as the nonsteroidal anti-inflammatory
      agents used in the present study.

PMID- 9169988
TI  - Release of amphotericin B from delivery systems and its action against fungal and
      mammalian cells.
AB  - Spectroscopic studies of four amphotericin B (AmB) lipid preparations--small
      negatively charged unilamellar vesicles "AmBisome", positively charged
      oligolamellar liposomes "Ampholiposomes", AmB Lipid Complex "L-AmpB33"--and AmB
      association with gamma cyclodextrin demonstrated that the composition of drug
      delivery system directly influences AmB organization. The aggregation state and
      release in external medium of AmB was monitored by circular dichroism and UV
      visible absorption. AmB short-term activity against Candida albicans (K+ leakage)
      was found to be correlated with the amount of free AmB released from lipid
      preparations. These data seem to indicate that lipid composition influences anti
      Candida albicans activity, by modulation of AmB binding to lipids.

PMID- 9169989
TI  - A long-circulating co-polymer in "passive targeting" to solid tumors.
AB  - A co-polymer of O-methyl polyethylene(glycol)-O'-succinate (MPEGs, m.w. 5100) and
      poly-l-lysine (PL, median m.w. 32700, degree of polymerization 256) has been
      synthesized by covalent grafting. The resultant MPEGs-PL (30% modification degree
      of epsilon-amino groups) had a hydrodynamic diameter corresponding to a 690 kD
      protein. Free amino groups (180/mol of the co-polymer) were used for conjugation
      of diethylene pentaacetic or succinic acid residues to MPEGs-PL. The potential of
      the resultant compound as a carrier of therapeutic and diagnostic drugs was
      studied using a rodent carcinoma models. The co-polymer had a blood pool half
      life of 36h in adenocarcinoma-bearing rats. Radioactively labeled preparations
      were resistant to trans-chelation with apotransferrin and stable in blood for 24
      h. The co-polymer accumulated in solid tumors at the level of 1.5-2% injected
      dose/g of tumor in 24 h. At that time, 34-40% of the accumulated polymer was
      associated with tumor cell fraction. The co-polymer non-covalently associated
      with cis-diamminedichloroplatinum(II), showed a cytostatic effect against mouse
      F9 carcinoma, and induced a reversal in tumor growth after intravenous
      administration.

PMID- 9169990
TI  - Human serum albumin as a probe for surface conditioning--a study of the ageing
      effect.
AB  - I125 radiolabelled HSA (HSA-I125) was utilised as a probe to quantify protein
      adsorption onto polystyrene (PS) and Poloxamine 908 coated PS (PS-908) particles.
      Upon ageing of the HSA-I125 a dramatic increase in the amount of protein adsorbed
      onto the two particle systems was observed. This phenomenon was not due to
      lability of the protein-radionuclide bond and no modifications in the secondary
      structure of the native and radiolabelled protein could be identified which could
      explain this unusual ageing effect. Using the amount of protein adsorbed to the
      uncoated particles as a control for each time point, it was possible to
      reproducibily determine the amount of HSA adsorbed to the coated particles.

PMID- 9169991
TI  - Neandertal incisor beveling.
AB  - In discussions of the Neandertals, there has been repeated emphasis on the
      accelerated rate of attrition and the frequent presence of labial beveling of
      their incisors. Interpretations of this dental attrition have related it to
      paramasticatory and dietary uses of their anterior teeth as well as to aspects of
      their facial morphology. In light of this, we examined the rate of beveling (the
      angle between the labial and incisal surfaces) of central incisors relative to
      tooth wear in samples of Neandertals, Inuits and Puebloan Amerindians. I1s show
      little change in the beveling angle with wear and no significant differences
      between the samples. I1s, however, exhibit a consistent pattern of increased
      beveling with dental attrition, progressing rapidly until the crown height
      approximates its labiolinguinal cervical diameter, and then proceeding at a
      slower rate. All three samples exhibit a similar pattern. However, the
      Neandertals have significantly greater beveling in more worn teeth than either
      recent human sample, and the Inuits have nonsignificantly increased beveling
      relative to the Puebloans in these more worn I1s. In this, it is the degree of
      development of beveling, not the pattern of beveling, which differentiates the
      Neandertals. It is hypothesized that the differences between the Neandertals and
      recent samples could be the product of: (1) contrast in initial incisor
      procumbency, (2) a labial separation of the maxillary and mandibular incisal
      occlusal surfaces during edge-to-edge bite, and/or (3) a greater degree of
      interproximal wear promoting increased "posterior tipping" of the maxillary
      incisors. The last appears most likely.

PMID- 9169992
TI  - Body proportions in Late Pleistocene Europe and modern human origins.
AB  - Body proportions covary with climate, apparently as the result of climatic
      selection. Ontogenic research and migrant studies have demonstrated that body
      proportions are largely genetically controlled and are under low selective rates;
      thus studies of body form can provide evidence for evolutionarily short-term
      dispersals and/or gene flow. Following these observations, competing models of
      modern human origins yield different predictions concerning body proportion
      shifts in Late Pleistocene Europe. Replacement predicts that the earliest modern
      Europeans will possess "tropical" body proportions (assuming Africa is the center
      of origin), while Regional Continuity permits only minor shifts in body shape,
      due to climatic change and/or improved cultural buffering. This study tests these
      predictions via analyses of osteometric data reflective of trunk height and
      breadth, limb proportions and relative body mass for samples of Early Upper
      Paleolithic (EUP), Late Upper Paleolithic (LUP) and Mesolithic (MES) humans and
      13 recent African and European populations. Results reveal a clear tendency for
      the EUP sample to cluster with recent Africans, while LUP and MES samples cluster
      with recent Europeans. These results refute the hypothesis of local continuity in
      Europe, and are consistent with an interpretation of elevated gene flow (and
      population dispersal?) from Africa, followed by subsequent climatic adaptation to
      colder conditions. These data do not, however, preclude the possibility of some
      (albeit small) contribution of genes from Neandertals to succeeding populations,
      as is postulated in Brauer's "Afro-European Sapiens" model.

PMID- 9169994
TI  - Age at death of Gibraltar 2.

PMID- 9169993
TI  - A multivariate analysis of Pleistocene hominids: testing hypothesis of European
      origins.
AB  - Multivariate analysis of intra- and inter-group variability in Middle and Upper
      Pleistocene human remains, based on facial traits, show close affinities between
      Upper Palaeolithic and Mesolithic samples, which are clearly distinct from Lower
      Palaeolithic and Neanderthal samples. The between-group differences observed were
      significant, although no sexual differentiation was considered. This allowed the
      classification of the fossil remains by discriminant analysis. A modern metrical
      pattern can be recognized for the Upper Palaeolithic sample, falling within the
      variability of anatomically modern humans. The samples from Skhul and Qafzeh,
      although exhibiting some plesiomorphous traits, also show modern-like metrical
      traits. The analysis strongly support a monophyletic origin for modern humans.

PMID- 9169995
TI  - New Kohatius (Omomyidae) from the Eocene of Pakistan.

PMID- 9169996
TI  - Comments on matrix permutation tests in the evaluation of competing models for
      modern human origins.

PMID- 9169997
TI  - Effect of high-performance liquid chromatography on plasma angiotensin II
      measurements in treated and untreated normotensive and hypertensive patients.
AB  - BACKGROUND: Angiotensin II (Ang II) levels are normally very low in human plasma,
      approximately 5 pg/ml. They are usually measured by radioimmunoassay after
      extraction and concentration. An additional high-performance liquid
      chromatography (HPLC) step is reportedly necessary for accurate measurement but
      it is laborious and time-consuming, severely limiting the number of samples that
      can be assayed. OBJECTIVE: To investigate whether the HPLC step was necessary for
      measuring Ang II in human plasma samples in our laboratory using our own Ang II
      antiserum. DESIGN: Human plasma Ang II levels, measured with and without the HPLC
      step, were compared in two different studies. Since the action of renin is the
      rate-limiting step in the production of Ang II in plasma, the relationships of
      plasma renin activity (PRA) to Ang II levels measured with and without HPLC were
      also evaluated. In the first study, 108 blood samples were collected from 29
      hypertensive patients during placebo or treatment with the Ang II antagonist BMS
      186295. In the second study blood samples were collected from 12 normal subjects
      before and during beta-adrenergic blockade. RESULTS: In samples collected during
      angiotensin II antagonism, which predictably increased plasma Ang II levels, a
      highly significant relationship between the Ang II measurements with and without
      HPLC was found (y = 0.99x + 1.7; r = 0.97, P < 0.001). The y intercept of 1.7
      pg/ml suggested that the nonspecific immunoreactivity was close to 2 pg/ml in
      samples assayed without the HPLC step. During beta-adrenergic blockade, which
      predictably suppressed plasma renin levels, highly significantly linear
      relationships between HPLC and non-HPLC Ang II measurements (y = 1.3x + 1.6; r =
      0.93. P < 0.001, n = 16) and between non HPLC Ang II and PRA (y = 1.9x + 1.7; r =
      0.73, P < 0.001, n = 108) were again found. The relationship between PRA and HPLC
      Ang II was also highly significant (y = 1.4x + 0.04; r = 0.92, P < 0.001, n =
      16), but the y intercept was significantly lower (P < 0.001), approaching zero,
      indicating the removal of nonspecific immunoreactivity during the HPLC step.
      CONCLUSIONS: These results demonstrate once more that, when using polyclonal
      antibody 182, the accuracy of the Ang II measurement in human plasma is improved
      by the inclusion of a HPLC step, especially for samples with Ang II levels in the
      normal-to-low range. They also show that plasma Ang II and PRA increase or
      decrease proportionally during treatment with Ang II antagonists or beta
      adrenergic blockade, respectively.

PMID- 9169998
TI  - Use of Fourier shape descriptors to improve the reproducibility of echographic
      measurements of arterial intima-media thickness.
AB  - BACKGROUND: A major source of error in the longitudinal assessment of the intima
      media thickness (IMT) is the difficulty in retrieving the same echographic view
      of the vessel. OBJECTIVE: To present a method for increasing the reproducibility
      of IMT measurements by ultrasound in large arteries. METHOD: The Fourier
      descriptor is a well-known means of describing an object's shape. By means of the
      discrete Fourier transform (DFT), the shape was represented in a frequency
      domain; the computational advantages of the DFT then permitted a measure of
      unlikeness between different shapes (the 'distance' measure; DM) to be defined
      and used as a criterion for reproducing the contour. When the sonographer
      compared successive images of a complex vascular segment, like the carotid
      bifurcation, the identity of the echographic cut was deduced from the identity of
      the vessel's contour. The best match of the baseline image was the view that
      minimized the contour DM. RESULTS: Preliminary studies in the carotid artery
      bifurcations of eight subjects showed that the DM responds to systematic
      variations in the ultrasound interrogation angle and reveals minimal changes in
      transducer position. Duplicate scans of 12 subjects were performed by three
      sonographers with different strategies for acquisition of the same images: a low
      DM was associated with a low difference in pairs of IMT measurements. Data were
      classified into two groups (normal or borderline vessels with a pooled mean IMT
      of 0.62 mm and overtly thickened segments with a pooled mean IMT of 1.31 mm).
      When minimization of the DM was the criterion for the acquisition of replicate
      scans, the mean absolute difference of paired data for the mean IMT of the distal
      common carotid artery was 0.03 +/- 0.02 mm for the first group and 0.06 +/- 0.03
      mm for the second group. This is a significant reduction in comparison with non
      quantitative alternative criteria for image reproduction. For the maximum IMT of
      the same segments the mean absolute differences were 0.07 +/- 0.03 and 0.13 +/-
      0.06 mm in the first and second groups, respectively. CONCLUSION: This method can
      be applied to the serial assessment of single atherosclerotic segments. The
      computational time is negligible. By reducing the scatter in sequential IMT data,
      longitudinal investigations (e.g. of the results of antihypertensive therapy)
      with shorter durations and smaller sample groups may be rendered feasible.

PMID- 9169999
TI  - Hyperinsulinemia and clustering of cardiovascular risk factors in middle-aged
      hypertensive Finnish men and women.
AB  - OBJECTIVE: To examine the relationship between hyperinsulinemia and clusters of
      cardiovascular risk factors in middle-aged hypertensive patients. DESIGN: A
      population-based study. SETTING: Pieksamaki District Health Center, and the
      Community health Center of the city of Tampere, in central Finland. SUBJECTS:
      Hypertensive men and women aged 36, 41, 46, and 51 years (n = 18) in the town of
      Pieksamaki, and a normotensive control population of 177 subjects aged 40 and 45
      years in the city of Tampere. MAIN OUTCOME MEASURES: Clusters of obesity (body
      mass index > 30.0 kg/m2), abdominal adiposity (waist:hip ratio > 1.00 for men and
      > 0.88 for women), hypertriglyceridemia (> 1.70 mmol/l), a low level of high
      density lipoprotein cholesterol (< 1.0 mmol/l in men and < 1.20 mmol/l in women)
      and abnormal glucose metabolism (impaired glucose tolerance or noninsulin
      dependent diabetes as defined by World Health Organization criteria) according to
      statistical quartiles of the fasting plasma insulin concentration. RESULTS: Among
      the hypertensives, there was a 2.0- to 3.6-fold higher risk of having a
      clustering of the insulin-resistance associated cardiovascular risk factors
      compared with that of the normotensives. Among the hypertensive subjects in the
      highest quartile of fasting plasma insulin there was a six- to 12-fold increase
      in risk associated with having two or more insulin resistance-associated
      cardiovascular risk factors compared with the subjects in the lowest quartile.
      There was a positive correlation between a high number of ascertained risk
      factors and high levels of fasting plasma insulin. CONCLUSION: In clinical
      practice, knowledge of the close relationship between risk-factor cluster status
      and fasting plasma insulin levels offers a tool to evaluate the occurrence of
      hyperinsulinemia in middle-aged hypertensive men and women.

PMID- 9170000
TI  - The response of renal plasma flow to angiotensin II infusion in a population
      based sample and its association with the parental history of essential
      hypertension.
AB  - BACKGROUND: Results from previous studies suggested that a blunted response of
      renal plasma flow (RPF) to angiotensin II infusion during a high-sodium diet (a
      phenotype associated with nonmodulation) is an intermediate phenotype for
      essential hypertension. OBJECTIVE: To determine whether RPF traits used to
      investigate nonmodulation have the characteristics of intermediate traits when
      examined in a population-based sample of adults aged 20-49.9 years. DESIGN AND
      METHODS: We examined the frequency distribution of baseline RPF and of its
      response to All infusion using maximum-likelihood commingling analysis in order
      to investigate the null hypothesis that the distributions of these traits are
      unimodal. We also examined the null hypothesis that there is no association
      between these candidate intermediate traits and the parental history of essential
      hypertension. RESULTS: There was some evidence for the commingling of multiple
      distributions underlying these traits both for women and for men but the
      commingled distributions overlapped substantially and the inferences about the
      commingling of distributions were sensitive to the method of RPF measurement,
      exclusion of outliers, and the method of adjustment for concomitants. There was
      no statistically significant association between any of the RPF traits and a
      parental history of essential hypertension. CONCLUSIONS: There is not
      sufficiently strong evidence to advocate the use of this set of intermediate
      traits to identify high-risk individuals or to relate genetic variation to the
      variation in risk of essential hypertension within this age range in the
      population at large.

PMID- 9170001
TI  - Relationship between renal plasma flow response to angiotensin II and blood
      pressure in a population-based sample.
AB  - OBJECTIVE: To assess whether interindividual variation in renal plasma flow or in
      its response to angiotensin II infusion is associated with interindividual
      differences in blood pressure in a population-based sample of 287 non-Hispanic
      whites (143 women and 144 men), aged 20-49.9 years. METHODS: After seven days of
      eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by
      measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg
      per min angiotensin II. Multiple linear regression methods were used to assess
      whether measures of the renal plasma flow and of its response to angiotensin II
      infusion were predictive of systolic or diastolic blood pressures measured prior
      to administration of the high-sodium diet, on day 6 of the high-sodium diet, or
      during the renal clearance procedure on day 7 prior to angiotensin II infusion.
      RESULTS: There was some evidence that measures of the renal plasma flow and of
      its response to angiotensin II infusion during the high-sodium diet were
      statistically significant predictors of measures of blood pressure in women;
      there was less evidence for this for blood pressures in men. Interindividual
      variation in measures of the renal plasma flow and of its response to angiotensin
      II infusion explained less than 10% of the interindividual variation in any
      measure of the blood pressure in both sexes. CONCLUSION: These results suggest
      that interindividual variation in renal plasma flow ad in its response to
      angiotensin II infusion during a high-sodium diet will be of limited utility in
      elucidating the basis for interindividual differences in blood pressure.

PMID- 9170002
TI  - Genetic variants of the renin-angiotensin system and ambulatory blood pressure in
      essential hypertension.
AB  - OBJECTIVE: To examine whether the angiotensinogen M235T and angiotensin
      converting enzyme insertion/deletion (I/D) variants are related to the severity
      of hypertension in patients with established essential hypertension. DESIGN: A
      cross-sectional study. SETTING: The hypertension clinic of the Benjamin Franklin
      University Hospital, Free University of Berlin. PARTICIPANTS: Three hundred and
      forty-three consecutive Caucasian patients who presented with treated or
      untreated (n = 115) hypertension were enrolled into the study. Twenty-two
      patients were excluded from analysis because they had secondary hypertension.
      MAIN OUTCOME MEASURES: Angiotensinogen M235T and angiotensin-converting enzyme
      I/D genotypes, 24 h ambulatory blood pressure values, the number of
      antihypertensive medications administered and left ventricular dimensions
      assessed by two-dimensional echocardiography. RESULTS: Neither the
      angiotensinogen nor the angiotensin converting enzyme genotype was related
      significantly to the average ambulatory blood pressure and left ventricular
      dimensions in hypertensives. Furthermore, neither the number of antihypertensive
      medications administered to treated patients nor blood pressure levels in
      untreated patients (n = 115) differed significantly between the genotypic groups.
      CONCLUSIONS: These results do not support the hypothesis that the studied
      molecular variants of the renin-angiotensin system may represent clinically
      useful markers of the severity of hypertension in Caucasians with established
      essential hypertension.

PMID- 9170003
TI  - Sodium intake regulates renin gene expression differently in the hypothalamus and
      kidney of rats.
AB  - OBJECTIVE: To elucidate the different effects of sodium intake on renin messenger
      RNA (mRNA) in the hypothalamus and the kidney and to investigate the role of
      hypothalamic renin in sodium-induced hypertension. DESIGN AND METHODS: We
      investigated the expression of the renin gene in the hypothalamus and the kidney
      of rats with altered sodium intake and those administered either
      deoxycorticosterone acetate (DOCA) or sodium. Diets containing a high (8% NaCl),
      normal (2% NaCl), or low (0.2% NaCl) amount of sodium were administered to 12
      week-old male Wistar rats for 10 days or 8 weeks before the rats were killed.
      Male Wistar rats administered either DOCA or 1% NaCl were killed 2 weeks (during
      the prehypertensive stage) or 6 weeks (during the hypertensive stage) after the
      start of treatment. The hypothalamus and kidneys were excised for extraction of
      total RNA. Competitive polymerase chain reaction of renin mRNA and deletion
      mutated renin RNA was performed, and the renin mRNA concentration was calculated.
      RESULTS: A high sodium intake for 10 days increased the renin mRNA in the
      hypothalamus; the hypothalamic renin mRNA had not been suppressed after 8 weeks
      of a high sodium intake despite the lowering in renal renin mRNA. Renin mRNA
      levels in the hypothalamus were not suppressed either in the prehypertensive or
      in the hypertensive stage in rats treated with DOCA or sodium, or both, although
      the renal renin mRNA was reduced in rats administered DOCA or sodium, or both,
      compared with that in sham-treated control rats, during both stages. CONCLUSIONS:
      The expression of the renin gene is regulated differently in the rat hypothalamus
      from that in the kidney. The constant expression of the renin gene in the
      hypothalamus during a chronic high sodium load might be related at least in part
      to the mechanism of the activated brain renin-angiotensin system in sodium
      induced hypertension.

PMID- 9170004
TI  - Role of kinins in basal and furosemide-stimulated renin secretion.
AB  - OBJECTIVE: There is evidence that kinins contribute to some of the renal,
      cardiovascular, and endocrine effects of the diuretic furosemide. The aim of the
      present study was to investigate the role of kinins in the regulation of renin
      secretion, blood pressure, and heart rate under resting conditions and after
      administration of furosemide. METHODS: The effects of icatibant, a potent,
      specific, and long-lasting bradykinin B2 receptor antagonist, on resting renin
      secretion, blood pressure, and heart rate, and on the responses of these
      variables to administration of furosemide, were investigated in conscious,
      chronically prepared rabbits. RESULTS: Injection of icatibant in doses of 0.1 and
      1.0 mg/kg blocked the hypotensive response to intravenous injections of
      bradykinin completely. The lower dose of icatibant decreased plasma renin
      activity in some animals, but did not alter their blood pressure or heart rate.
      The higher dose suppressed resting plasma renin activity from 10.2 +/- 2.2 to 5.6
      +/- 1.4 ng/ml/2 h (P < 0.01), without changing the blood pressure or heart rate.
      Injection of furosemide (2 mg/kg) caused a sustained increase i plasma renin
      activity from 6.7 +/- 1.6 to 15.9 +/- 3.3 ng/ml/2h (P < 0.01), a transient
      increase in mean arterial pressure from 72 +/- 3 to 78 +/- 3 mmHg (P < 0.05), and
      a sustained increase in heart rate from 228 +/- 8 to 253 +/- 6 bpm (P < 0.01).
      Neither dose of icatibant altered the cardiovascular and renin responses to
      furosemide. CONCLUSIONS: These results provide evidence that bradykinin B2
      receptors participate in the regulation of resting renin secretion, but not in
      the renin secretory or heart rate responses to furosemide.

PMID- 9170005
TI  - Effects of chronic losartan treatment on vascular reactivity in normotensive
      rats.
AB  - OBJECTIVE: To investigate the vasoactive properties of large (aorta) and small
      (mesenteric) arteries in vitro after chronic losartan treatment of normotensive
      rats, hence providing information on the role played by angiotensin II in
      vascular tone. METHODS: Wistar rats were treated with 10 mg/kg per day losartan
      for 3 weeks. Ring segments of thoracic aorta and mesenteric resistance arteries
      (200 microns diameter) were mounted in myographs and wall force measured
      isometrically. RESULTS: The mean carotid blood pressure was reduced significantly
      after chronic losartan treatment (108 +/- 3 mmHg, n = 17 versus 116 +/- 2 mmHg, n
      = 16 in control rats, P < 0.05). In the mesenteric resistance artery the
      contractile response to 125 mmol/l K+, phenylephrine and angiotensin II was not
      affected significantly by losartan treatment. A subcontractile concentration of
      angiotensin II (0.1 nmol/l) induced a significant potentiation of the response to
      0.03-100 mumol/l) phenylephrine (450 +/- 180 to 150 +/- 20% of the previous
      response to phenylephrine in control rats). This potentiation was attenuated
      significantly in the losartan group (240 +/- 80 to 100 +/- 15% of the previous
      response, P < 0.01 versus control rats). In the aorta, the response to 125 mmol/l
      K+ was not affected by chronic losartan treatment. The concentration required for
      the half-maximal effect for phenylephrine was increased significantly in the
      losartan group (0.51 +/- 0.11 mumol/l versus 0.17 +/- 0.03 mumol/l in controls
      rats; no change in maximum response) and the maximum response to angiotensin II
      was reduced significantly (0.7 +/- 0.08 mN/mg tissue versus 1.9 +/- 0.2 mN/mg
      tissue in control rats; the concentration for the half-maximal effect was not
      affected). Potentiation of phenylephrine-induced tone by 0.1 nmol/l angiotensin
      II (273 +/- 55 to 122 +/- 12% of the previous response in control rats) was
      attenuated significantly by losartan treatment (91 +/- 46 to 95 +/0 23% of the
      previous response, P < 0.01 versus control) CONCLUSIONS: Chronic administration
      of losartan could act on resistance arteries in normotensive rats by blocking the
      potentiation by angiotensin II of the agonist-induced tone.

PMID- 9170006
TI  - Effect of deoxycorticosterone acetate on blood pressure in relation to
      accumulation of low-density lipoprotein and fibrinogen by aorta and other tissues
      of normotensive Wistar rats.
AB  - OBJECTIVE: To evaluate the effect of different 4-week doses of
      deoxycorticosterone acetate (DOCA), together with 0.9% sodium chloride in the
      drinking water (DOCA-salt) on the blood pressure and on the accumulation of low
      density lipoprotein (LDL) and fibrinogen in artery walls ad other tissues in
      conscious, unrestrained, normotensive Wistar-Kyoto rats. METHODS: The
      accumulation of LDL labelled with 125I via the adduct tyramine cellobiose ([125I]
      TC-LDL) and of fibrinogen similarly labelled with 131I ([131I]-TC-fibrinogen) was
      compared in aortic walls, heart, liver, kidney, lung. skeletal muscle, and
      adrenal gland tissues during the final 24 h of a 4-week administration of DOCA
      salt, with vehicle-salt and saline as controls. RESULTS: In control and vehicle
      rats the blood pressure did not change significantly during the last 5 days of
      treatment. Administration of DOCA-salt produced a dose-dependent increase in
      blood pressure during the same period. DOCA-salt administration increased LDL
      accumulation in the aorta and the heart and decreased LDL accumulation in the
      adrenal gland compared with those in rats of the control and vehicle groups. DOCA
      salt administration did not affect fibrinogen accumulation significantly.
      CONCLUSION: DOCA-salt treatment produces an increase in arterial blood pressure
      accompanied by an increase in LDL accumulation by the aortic wall and heart and a
      decrease in LDL accumulation by the adrenal gland. These observations raise the
      possibility that one mechanism by which hypertension affects atherosclerosis is
      through increased LDL accumulation in arterial walls.

PMID- 9170007
TI  - Hypertension induced by foetal exposure to a maternal low-protein diet, in the
      rat, is prevented by pharmacological blockade of maternal glucocorticoid
      synthesis.
AB  - BACKGROUND: Hypertension and coronary heart disease are programmed by maternal
      undernutrition in utero. The feeding of low-protein diets to rats during their
      pregnancy results in higher blood pressure in the offspring from the age of
      weaning. OBJECTIVE: To determine whether a low-protein diet increases foetal
      exposure to glucocorticoids of maternal origin, resulting in altered hypothalamic
      pituitary-adrenal axis function and hypertension. DESIGN: Rats were fed an 18%
      casein diet (control) or a 9% casein diet (low protein) during pregnancy. Low
      protein-fed dams were injected with metyrapone to inhibit corticosterone
      synthesis or with metyrapone plus a replacement dose of corticosterone. The
      offspring of these pregnancies had their blood pressure determined when they were
      aged 7 weeks. METHODS: The systolic blood pressure was determined using an
      indirect tail-cuff method. Glucocorticoid action in the hypothalamus was measured
      using glycerol-3 phosphate dehydrogenase as a reference enzyme. RESULTS: Blood
      pressures of rats exposed to maternal low-protein diets in utero were elevated
      significantly relative to those of control rats. The animals that had been
      exposed to a maternal low-protein diet also exhibited increased glycerol-3
      phosphate dehydrogenase (GPDH) activity in the hypothalamus, whereas their
      pyruvate kinase activity was not changed. The offspring of rats injected with
      metyrapone did not have raised blood pressure or GPDH activities. Replacement of
      corticosterone during pregnancy had no effect upon the blood pressures and GPDH
      activities of male offspring, but it reversed the effects of metyrapone in female
      offspring. CONCLUSIONS: Exposure to a maternal low-protein diet in utero
      programmes hypertension in the rat. The data are consistent with the hypothesis
      that corticosteroids of maternal origin play a role in this programming effect.

PMID- 9170008
TI  - Role of vasopressin in essential hypertension: racial differences.
AB  - BACKGROUND: Arginine vasopressin (AVP), in addition to being an antidiuretic
      hormone, might also have pressor effects relevant to the maintenance of
      hypertension. Results from several experimental and clinical studies suggested
      that the pressor function of AVP is more important in low-renin hypertension and
      in the salt-loaded state and that it might be further maximized under sympathetic
      suppression. OBJECTIVE: To assess whether selective vasopressin receptor
      inhibition lowers the blood pressure in a racially diverse group of low-renin
      hypertensive subjects. METHODS: Thirty-nine hypertensive subjects (16 Caucasian,
      23 African-American) eating a 200 mmol/day sodium diet were administered a single
      intravenous dose of a selective vasopressin receptor antagonist and their blood
      pressure was monitored constantly for the ensuing 3 h. The protocol was repeated
      3 days later after treatment with a single oral dose of 0.4 mg clonidine.
      RESULTS: Of these patients, 54% had their blood sampled for determination of
      hormone profiles. African-Americans with hypertension had higher baseline plasma
      AVP levels than did Caucasians (1.13 +/- 0.05 versus 0.37 +/- 0.06 pg/ml,
      respectively, P < 0.05), and lower plasma renin activity (0.34 +/- 0.07 versus
      1.03 +/- 0.08 ng/ml per h, respectively, P < 0.05). Selective vasopressin
      receptor inhibition lowered the mean arterial pressure in African-Americans but
      not that in Caucasians (lowering by 28 +/- 4 mmHg in African-Americans versus
      lowering by 5 +/- 3 mmHg in Caucasians, P < 0.05). Moreover, vasopressin receptor
      blockade further reduced the arterial pressure in African-Americans but not that
      in Caucasians after pretreatment with clonidine. CONCLUSION: AVP seems to play a
      more important role as a pressor hormone in maintaining the elevation of arterial
      pressure in African-American hypertensives than it does in Caucasian
      hypertensives.

PMID- 9170009
TI  - Impaired renal haemodynamic response to amino acid infusion in essential
      hypertension during angiotensin converting enzyme inhibitor treatment.
AB  - OBJECTIVE: To determine whether hyperfiltration induced by amino acid infusion
      can be influenced by angiotensin converting enzyme (ACE) inhibition. DESIGN: We
      studied the acute effects of ramipril in 12 healthy control subjects and in 14
      patients with essential hypertension. We studied also the effects of 2 months'
      treatment with ramipril inn 12 patients with essential hypertension and performed
      a time-control study without amino acids infusion with 12 control subjects. The
      glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion
      of sodium (FENa) and fractional excretion of lithium (FELi) were determined
      during 6 clearance periods of 30 min each and amino acids infusion was
      administered during the last four periods. Plasma concentrations of angiotensin
      II, aldosterone, atrial natriuretic peptide (ANP), arginine vasopressin, insulin
      and glucagon were determined. RESULTS: Both the GFR and the RPF increased
      markedly in healthy subjects after amino acid infusion both with (GFR 7%, RPF 7%)
      and without ramipril (GFR 7%), RPF 8%), both P < 0.05. Ramipril administered
      acutely to essential hypertensives prevented the amino acid-induced increase in
      RPF [with ramipril 5% (NS), without ramipril 9% (P < 0.05)]. The GFR increased
      equally with (5%) and without (8%) ramipril (P < 0.20). ACE inhibition after 2
      months' treatment of essential hypertension blunted the amino acid-induced
      increase both in GFR and in RPF [with ramipril GFR 5% and RPF 3% (NS), without
      ramipril GFR 12%, RPF 11% (P < 0.05)]. The FENa did not change in all four
      experiments. The FELi, insulin and glucagon increased to the same extent in the
      first three experiments. ANP increased (P < 0.05) in control subjects both with
      and without ramipril; angiotensin II and aldosterone decreased significantly in
      control subjects without ramipril. CONCLUSIONS: The renal haemodynamic response
      both after acute and after short-term ACE inhibition is attenuated in essential
      hypertension. Presumably, this treatment makes the arterioles at the glomeruli
      unresponsive to subsequent amino acid infusion. This inhibition of
      hyperfiltration might be an important mechanism for the renal protective effect
      of ACE inhibition in some renal diseases.

PMID- 9170010
TI  - Drug compliance among hypertensive patients in Tabuk, Saudi Arabia.
AB  - OBJECTIVE: To estimate the compliance rate and associated factors among a
      population of hypertensive subjects registered in hospitals and primary health
      care centres. DESIGN: A prospective study carried out on a sample of hypertensive
      subjects. METHOD: Compliance with treatment by the study sample was measured
      using the pill-counting method. The reasons for noncompliance are listed and the
      status of blood pressure control among compliant and noncompliant subjects is
      reported. RESULTS: The compliance rate was 53.0%. It was associated positively
      with male sex, and negatively with older age, symptoms of illness and drug side
      effects. The degree of blood pressure control was worse among noncompliant
      subjects. Reasons for noncompliance included the asymptomatic nature of
      hypertension, a shortage of drugs, side effects, forgetfulness and lack of health
      education. CONCLUSIONS: The compliance rate was low in this study and was
      accompanied by inadequate blood pressure control among noncompliant subjects.
      Disoriented behavior regarding hypertension and its medications was observed.

PMID- 9170011
TI  - Mechanisms for the secretion of ANP.

PMID- 9170012
TI  - Isoniazid resistance and the point mutation of codon 463 of katG gene of
      Mycobacterium tuberculosis.
AB  - It has long been known that almost all isoniazid (INH) resistant mycobacteria
      lose the catalase and peroxidase activities along with reduced or no virulence
      for guinea pigs. Recently resistance to INH has become known to be associated
      with mutations of katG gene encoding the HPI (Hydroperoxidase I) type catalase
      and peroxidase. Among these mutations, the point mutation of codon 463 of katG
      gene is found frequently, and is suggested as being associated with INH
      resistance. Therefore we performed this study in order to confirm the correlation
      between the point mutation of codon 463 of the katG gene and INH resistance of M.
      tuberculosis in Korea. Fifty isolates, 32 of which were resistant to INH, and 18
      of which were sensitive to INH, were selected for this study. We used PCR-SSCP
      and RFLP analysis to detect the point mutation of the codon 463 of katG gene and
      confirmed the CGG (arginine) to CTG (leucine) mutation by direct sequencing
      analysis. Among 32 resistant isolates, 7 isolates (22%) had the same restriction
      pattern compared with that of the reference strain (H37Rv), and 25 isolates (78%)
      showed a different restriction pattern. Among 18 sensitive isolates, 7 isolates
      (39%) had the same restriction pattern compared with that of H37Rv, and 11
      isolates (61%) showed a different restriction pattern. These results suggest that
      the CGG to CTG change of codon 463 of katG gene of M. tuberculosis may be a
      polymorphism not related with INH resistance.

PMID- 9170013
TI  - Cytotoxicity and multinucleate giant cell formation in Chinese hamster lung
      fibroblast caused by crocidolite and chrysotile.
AB  - The mechanism of carcinogenic action of asbestos remains unclear but the physical
      properties of the fiber appear to be important in this process. Asbestos may
      cause multinucleate giant cell formation primarily by interfering with the normal
      course of mitosis. We evaluated the cytotoxicity and multinucleate giant cell
      formation induced by crocidolite and chrysotile in Chinese hamster lung
      fibroblast (V79 cell) with observation of phagocytic activities. Asbestos fibers
      were rapidly ingested by V79 cells and most fibers were inside the cells.
      Cytotoxicity was evaluated by observing inhibition of V79 cell proliferation with
      trypan blue exclusion test. For determination of frequency of multinucleate giant
      cells, the cells were treated with different doses of crocidolite or chrysotile
      for 72 hours. Crocidolite and chrysotile induced cytotoxicity in V79 cells in a
      dose-dependent manner. The pattern of inhibition of cell proliferation is similar
      for both types of fibers, but chrysotile was more potent at the highest level
      (20.0 micrograms/ml) of fiber concentration. There was a good relationship
      (regression coefficientcrocidolite = 0.02, P < 0.01; regression
      coefficientchrysotile = 0.04, P < 0.01) between the dose of both asbestos fibers
      and the frequency of multinucleate giant cells. Chrysotile was again more potent
      at inducing multinucleate giant cells in higher levels of fiber concentrations.
      We found that asbestos fibers were cytotoxic after phagocytosis and induced
      multinucleate giant cells by interfering mitosis.

PMID- 9170014
TI  - The etiology and clinical characteristics of mesenteric adenitis in Korean
      adults.
AB  - This study is aimed at investigating the etiology and clinical characteristics of
      mesenteric adenitis in Korean adults, prospectively. Clinical manifestations of
      fifteen patients who presented with the acute onset of right lower quadrant pain
      and sonographically enlarged mesenteric lymph nodes and normal appendix were
      evaluated. For etiologic diagnosis, stool culture, serologic test for Epstein
      Barr virus, and Widal test were performed. Colonoscopy with mucosal biopsies and
      microbial tissue cultures were performed in 12 of 15 patients. Of fifteen
      patients 6 were male and the average age was 29.9 (17 approximately 41) years.
      Associated symptoms were diarrhea (80%), fever (73%), nausea and vomiting (27%).
      Right lower quadrant tenderness was observed in all cases but rebound tenderness
      was observed only in 26.7% of the cases. Etiology was identified in 7 cases
      (47%): 2 Yersinia enterocolitica infection, 2 non-typhoidal Salmonella infection,
      2 tuberculosis, and 1 typhoid fever. In colonoscopic examination, signs of active
      inflammation were observed in 9 cases (75%) and inactive or normal findings in 3
      cases (25%). All of our patients, except for the patients with tuberculosis and
      typhoid fever who needed specific antibiotic therapy, improved spontaneously
      without using antibiotics. In conclusion, the etiology of mesenteric adenitis in
      Korean adults seems to be different from that of western countries. Furthermore,
      mesenteric adenitis in Korean adults is a clinical syndrome, frequently found in
      a relatively young age group, which improves spontaneously unless specific anti
      microbial agents are indicated by microbiological tests, such as tuberculosis or
      typhoid fever.

PMID- 9170015
TI  - Acute therapy for hyperkalemia with the combined regimen of bicarbonate and
      beta(2)-adrenergic agonist (salbutamol) in chronic renal failure patients.
AB  - This study was aimed to evaluate the efficacy of combination therapy of
      bicarbonate and salbutamol for hyperkalemia in 9 hemodialysis patients.
      Simultaneous administration of 8.4% sodium bicarbonate (i.v., 2 mEq/kg) for 1/2
      hour and salbutamol (15 mg) in nebulized form for 10 min was compared with
      treatment modality of either bicarbonate or salbutamol alone. Infusion of sodium
      bicarbonate induced a significant rise in plasma bicarbonate from 17.3 +/- 3.2 to
      22.1 +/- 2.4 mEq/L (p < 0.01), but was ineffective in lowering plasma potassium (
      0.13 +/- 0.06 mEq/L). As expected, salbutamol significantly lowered plasma
      potassium (-0.57 +/0 0.03 mEq/L, p < 0.02 vs. basal value) in all except 2
      patients. The combined regimen of bicarbonate and salbutamol to a total 9
      patients including 2 patients without hypokalemic effect to salbutamol alone
      revealed a substantially greater fall in plasma potassium (-0.96 +/- 0.08 mEq/L,
      p = 0.000 vs. either drug alone) accompanied with significant increase in plasma
      bicarbonate and blood pH. Treatment with salbutamol or the combined regimen
      produced slight increases in heart rate but not in blood pressure. It is
      concluded that the combined regimen of bicarbonate and beta(2)-adrenergic agonist
      (salbutamol) could be recommended as an efficient alternative for severe
      hyperkalemia in uremic patients, and is suggested that the enhanced transcellular
      hypokalemic effects of salbutamol in this combined regimen with bicarbonate would
      be related to the activation of Na-K pump with acute correction of underlying
      metabolic acidosis.

PMID- 9170016
TI  - Effects of altered body fluid balance and high blood pressure on the plasma brain
      natriuretic peptide in rats.
AB  - The present study was aimed to investigate the regulatory mechanisms of BNP
      release. Effects of acute and chronic perturbations in body fluid balance,
      changes in BP, and regulatory roles of NO and endothelin systems on BNP release
      were examined in rats. Although acute extracellular volume expansion did not have
      significant effects on plasma BNP, prolonged high-salt intake increased plasma
      BNP levels. Plasma BNP levels were also higher in 2K1C rats compared with the
      control. Although infusion of L-NAME increased the plasma BNP in control, it did
      not further affect the plasma BNP in rats with high-salt intake. Although L
      arginine (20 mg.kg-1 per min) per se did not have significant effects on plasma
      BNP, it blocked the stimulatory effect of L-NAME (200 micrograms.kg-1 per min).
      Plasma BNP was severalfold increased following a single injection of endothelin
      (0.3 micrograms/kg) in normal and high-salt intake groups, the magnitude of which
      was not significantly affected by the high-salt intake. Although indomethacin did
      not have significant effects on plasma BNP in normal rats, it blocked the
      stimulatory effect of 2K1C hypertension. It is concluded that BNP is regulated by
      chronic changes in body fluid balance and blood pressure. It is also suggested
      that endothelin and NO systems may directly regulate the secretion of BNP in
      vivo. An endogenous prostaglandin synthesis may be involved in the stimulated
      release of BNP in hypertension.

PMID- 9170017
TI  - Arthroscopic decompression for subacromial impingement syndrome.
AB  - Arthroscopic decompression and cuff debridement was performed on 47 cases in 45
      consecutive patients with either stage II or stage III impingement syndrome: 19
      with no actual tear of the cuff (stage II); 13 with a partial thickness tear
      (stage IIIa); 10 with complete tear less than 3 cm long (stage IIIb); and 5 with
      complete tear longer than 3 cm (stage IIIc). Patients were classified into
      impingement syndrome without tear (Group I), impingement syndrome with partial
      thickness tear (Group II), and impingement syndrome with full thickness tear
      (Group III). Group I had 19 cases, group II had 13 cases, and group III had 15
      cases. Patients were followed up for an average of 39.3 months (24 approximately
      62 months). In group I, postoperative UCLA ratings improved in 18 cases (95%) to
      satisfactory result rate. In group II, 11 patients (85%) had improvement to
      satisfactory result rate. In group III, 12 cases (80%) had improvement to
      satisfactory result rate. The arthroscopic subacromial decompression and rotator
      cuff debridement was effective in the treatment of subacromial impingement
      syndrome.

PMID- 9170018
TI  - In-vivo study on the harmful effect of the extremely low frequency unipolar
      pulsating magnetic field in mice.
AB  - We studied the biological effect of a magnetic field on murine brain and kidney.
      Magnetic field we used was generated by Magno-DR apparatus (Hanil Co., Korea)
      which produced a high density unipolar square pulsating magnetic field, about 0.3
      approximately 0.5 Tesla at 7 Hertz. Animals were placed in the chamber of the
      machine for various times from 4 hours to 24 hours. Histological sections of
      brain and kidney were made after perfusion fixation with paraformaldehyde. The
      light microscopic examination showed eosinophilic change of cytoplasm and
      positive immunohistochemical reaction to amyloid precursor protein in the neurons
      of the cerebral cortex. However, the thalamus and brain stem were less affected.
      The changes in the brain was seen in the mouse exposed more than 12 hours. The
      renal tubular epithelium showed degenerated tubules scattered in cortical area
      but little change was noted in glomeruli in the cortex and collecting tubules in
      the medulla. Immunohistochemistry of the kidney showed weakly positive reaction
      for the amyloid precursor protein in the distal tubular epithelium after 4 hours
      of exposure. These data suggest that strong pulsating magnetic fields could
      induce deleterious effect on the murine brain tissue and renal cortical tubules.

PMID- 9170019
TI  - Diagnostic potential of laser-induced autofluorescence emission in brain tissue.
AB  - Laser-induced autofluorescence measurement of the brain was performed to assess
      its spectroscopic properties and to distinguish brain tumors from the normal
      tissues. The excitation-induced emission spectra were plotted on a 2-dimensional
      map, the excitation-emission matrix, to determine the excitation wavelengths most
      sensitive for the spectroscopic identification of brain tumors. The excitation
      emission matrices of various types of human brain tumors and normal brain samples
      lead to the selection of three fluorescence peaks at 470, 520, and 630 nm,
      corresponding excitation light at 360, 440, and 490 nm, respectively for
      comparing the autofluorescence signatures of brain tissue. The fluorophores most
      likely related to each of these peaks are NAD(P)H, various flavins, and
      porphyrins, respectively. In vivo studies of rat gliomas showed that "NAD(P)H",
      "flavin", and "porphyrin" fluorescence were lower in gliomas than in normal
      brain. This finding suggests that there are certain relationship between brain
      tissue autofluorescence intensity and metabolic activity. In vitro human normal
      brain tissue fluorescence signals were lower in gray matter than in white matter
      and "NAD(P)H" fluorescence were lower in all measured human brain tumors than in
      normal brain. "Flavin" and "porphyrin" fluorescence in the neoplastic tissues was
      lower or higher than normal tissue depending on their nature. In conclusion, the
      fluorescence spectroscopic diagnostic system might be able to distinguish brain
      tumors from the normal brain tissue. The results of this study need to be
      verified and the investigation extended to human brain tumors in the operating
      room.

PMID- 9170020
TI  - Cardiac tamponade due to a rupture of the coronary arteriovenous aneurysm--a case
      report.
AB  - We experienced an unusual case of cardiac tamponde caused by a rupture of the
      coronary arteriovenous aneurysm in a 54-year-old woman. The patient was suffered
      from sudden chest pain and syncope, and was initially managed by
      pericardiocentesis following an echocardiogram which revealed a massive
      pericardial effusion with signs of cardiac tamponade. She was referred to our
      hospital under the impression of aortic dissection with cardiac tamponade. She
      underwent an emergency operation and was found to have a 2 x 2 cm sized bleeding
      cystic mass protruding from the proximal anterior descending coronary artery. The
      aneurysm was excised and the openings connected with the coronary artery and
      right ventricular outflow tract were closed with sutures from the inside of
      aneurysm. Subsequent coronary arteriography supported the diagnosis.

PMID- 9170021
TI  - Neonatal adenoviral pneumonia--report of three autopsy cases.
AB  - Adenovirus pneumonia, while common in infancy and childhood, is rarely documented
      but may be fatal in the neonatal period. In regard to the serious outcome and no
      responsiveness to common anti-viral agents, adenovirus infection should be
      considered in the differential diagnosis of pneumonia in neonates. We report
      three cases of fatal neonatal adenovirus pneumonia, all of which were diagnosed
      by postmortem examination. Two patients were born by cesarean section at 35 or 36
      weeks of gestation, and the other was a 5100 gm postmature baby born by vaginal
      delivery at 43 weeks of gestation. Respiratory insufficiency was detected just
      after birth or in the immediate postnatal period, and was associated with
      lethargy and chest X-ray findings of pneumonic infiltration. The postmortem
      findings of these patients were remarkably consistent and characterized by
      predominant lung involvement. The lungs showed diffuse massive consolidation with
      scattered patchy hemorrhage, and histologically revealed multifocal necrotizing
      alveolitis and/or bronchiolitis, often with hemorrhage. Alveolar lining cells and
      desquamated cells contained numerous smudge ells and many cells with
      characteristic inclusion bodies. Electron microscopy revealed that these
      inclusion bodies consisted of arrays of icosahedral particles of adenovirus. It
      is unusual that one of the patients, who was born by cesarean section without any
      evidence of prenatal infection, developed adenoviral pneumonia; this indicates
      that infection may occur in the immediate postnatal period as well as during
      passage of the birth canal.

PMID- 9170022
TI  - Guillain-Barre like syndrome associated with acute renal failure and
      thrombocytopenia following acute viral hepatitis A.
AB  - We reported a 43-year-old woman who showed a Guillain-Barre like syndrome
      associated with acute renal failure (ARF) and thrombocytopenia following acute
      viral hepatitis A(HA). The clinical feature was acute progressive and of
      ascending symmetric paraparesis which developed 5 days after gastrointestinal
      infection. Neurologic examination showed flaccid paraparesis, areflexia in all
      extremities and limitation on the straight leg raising test. Laboratory
      examinations showed the evidences of ARF, thrombocytopenia and HA. EMG findings
      suggested a polyradiculopathy. Renal biopsy showed the findings of acute
      interstitial nephritis, acute tubular necrosis and IgA deposition nephropathy.
      She was treated by plasmapheresis and platelet transfusion, then showed a rapid
      improvement, and has been well without further complication after discharge.

PMID- 9170023
TI  - Renal potassium wasting and hypocalciuria ameliorated with magnesium repletion in
      Gitelman's syndrome.
AB  - A woman aged 45 years was presented with hypokalemic metabolic alkalosis and
      hypomagnesemia associated with renal potassium and magnesium wasting. Her 24-hour
      urinary calcium excretion was strikingly low despite normocalcemia and normal
      creatinine clearance, which is one of characteristic findings of Gitelman's
      syndrome (GS). She was evaluated for the responses following Mg supplementation
      for 10 days, which showed marked increments in serum potassium and magnesium as
      well as improvements of the degree of renal potassium wasting and hypocalciuria.
      This amelioration of abnormal biochemical pictures in this patient after Mg
      supplementation proposes that the hypokalemia with renal potassium wasting and
      hypocalciuria may be caused by abnormal Mg metabolism.

PMID- 9170024
TI  - Acute myopathy induced by colchicine in a cyclosporine-treated renal transplant
      recipient--a case report and review of the literature.
AB  - We report a case of colchicine-induced myopathy related to short-term, customary
      administration of colchicine. A 49-year-old male was admitted because of muscle
      weakness and myalgia that had developed 10 days previously. He had received renal
      transplantation 5 years previously and took cyclosporine as an immunosuppressant.
      Two weeks before admission, gout was developed and he took colchicine (1.2 mg
      b.i.d) by himself for three days. Colchicine-induced myopathy was clinically
      suspected, and colchicine intake was stopped immediately. After that, clinical
      symptoms gradually improved and serum muscle enzyme returned to normal. In this
      case, mild renal dysfunction and drug interaction between cyclosporine and
      colchicine wee suggested to be the precipitating factors of colchicine-induced
      myopathy.

PMID- 9170025
TI  - Choroid plexus carcinoma in an infant.
AB  - Choroid plexus carcinoma is a rare tumor and has a strong tendency to spread
      along the cerebrospinal fluid pathway. The tumor frequently occurs in infants.
      Radiation therapy is not indicated in infants and the response of this tumor to
      chemotherapy is variable. Therefore, surgical removal plays a major role in the
      management of this tumor, especially in infants. A 2-month-old girl with an acute
      communicating hydrocephalus was presented. Through the left posterior parietal
      transcortical approach, a choroid plexus carcinoma which had poor demarcation
      from the posterior thalamus and the medial wall of the lateral ventricle was
      subtotally (> 95%) removed. Postoperatively a ventriculoperitoneal shunt was
      inserted. Chemotherapy was refused. Magnetic resonance imaging taken at 11 months
      after surgery showed multiple intracranial seeding of the tumor. She was in a bed
      ridden state. This case revealed the aggressive behaviour of choroid plexus
      carcinoma in an infant and the dismal result of subtotal removal alone, though it
      is rather radical.

PMID- 9170026
TI  - Encephalitis and polyradiculoneuritis following rubella virus infection--a case
      report.
AB  - Amongst neurological complications of rubella virus infection,
      polyradiculoneuritis as well as encephalitis is very rare. Only one case of
      postrubella polyradiculoneuritis combined with encephalitis has been reported to
      our knowledge. A 17-years-old male presented with suspected meningoencephalitis
      in a recent epidemic of rubella in a southern district of Korea. He developed
      symmetrical hyporeflexic weakness of all four extremities with urinary
      disturbance several days later. Rubella IgM antibody titer (enzyme linked
      immunosorbent assay) was 58 AU/mL in serum and 12 AU/mL in cerebrospinal fluid.
      Electrophysiologic studies showed peripheral polyradiculoneuropathy with
      multifocal conduction block. Considering the involvement of the central nerve as
      well as the peripheral nerve in an adult patient, this case is thought to be
      valuable in view of the pathophysiology of neurologic complication in rubella
      virus infection.

PMID- 9170028
TI  - Ovarian fibromas and cystadenofibromas: MRI features of the fibrous component.
AB  - Ovarian fibromas and cystadenofibromas are neoplasms that share a similar
      distinctive tissue component of dense fibrous tissue. We sought to describe the
      MRI features of these neoplasms and to determine if the fibrous component shows
      distinctive characteristics. Fourteen patients in whom MR images performed with
      multicoil and fast-spin-echo images and who subsequently underwent surgery for
      resection of ovarian fibromas or cystadenofibromas were identified from two
      institutions. Five patients had ovarian fibromas, and nine patients had fourteen
      cystadenofibromas. 1.5-T MR studies used T1-weighted spin echo and multiplanar T2
      weighted fast-spin-echo images, with fat saturation gadolinium-enhanced fast
      multiplanar gradient-echo images in seven patients. Studies were reviewed for
      findings of low (approximately equal to skeletal muscle) signal intensity solid
      components on T2-weighted images, characteristics of gadolinium enhancement, and
      associated endometrial findings. Images were obtained ex vivo from three adnexal
      surgical specimens with an 8-cm field of view and correlated with histology. All
      five of the fibromas showed predominantly very low signal intensity, similar to
      skeletal muscle, on T2-weighted images. Two of five fibromas were in patients
      with endometrial polyps and increased amounts of fluid in the pelvis. Thirteen
      cystadenofibromas were multicystic masses with bands of very low signal intensity
      ranging from 2 to 20 mm in the wall of the mass, and one was predominantly solid
      fibrous tissue. Pathologic correlation with specimen images showed that the low
      signal intensity material was the subepithelial fibrous component of the
      cystadenofibromas. Fibrous components of ovarian fibromas and cystadenofibromas
      are demonstrable by MR as solid components representing fibrous tissue of very
      low signal intensity on T2-weighted images.

PMID- 9170027
TI  - Microvessel density of invasive breast cancer assessed by dynamic Gd-DTPA
      enhanced MRI.
AB  - It has been postulated that the rapid enhancement demonstrated by breast
      carcinomas after administration of contrast media is a direct result of tumor
      angiogenesis. However, to date, little quantitative data have been published to
      support this view. A retrospective study has been undertaken to compare dynamic
      contrast-enhanced data obtained from 40 patients with microvessel density (MVD)
      evaluated in specimens immunohistochemically stained with a factor VIII related
      antigen. The dynamic data were analyzed quantitatively using both simple indices
      of enhancement and a two-compartment kinetic model. A moderate but significant
      correlation was demonstrated between initial enhancement and MVD, and this
      correlation strengthened when node-positive tumors were considered in isolation
      (r = .77, P < .0005). However, the data showed considerable variability. The
      enhancement characteristics of the tumors could not be explained solely by their
      MVD; therefore, MRI cannot be used to predict MVD in vivo. Further work is
      required to address the exact relationship between contrast-enhanced MRI and
      tumor angiogenesis.

PMID- 9170029
TI  - Delineation of liver necrosis using double contrast-enhanced MRI.
AB  - The purpose of this study was to demonstrate the potential usefulness of the
      combination of gadolinium and dysprosium to enhance the different between normal
      and necrotic liver tissue. Small regions of acute necrosis were induced by
      injecting 200-300 microliters of 95% alcohol into the liver of 26 rats. MRI was
      performed 24 hours after necrosis induction, before and immediately after
      injection of one or both contrast agents. Using a mixed T1/T2-weighted sequence,
      the signal intensity of (SI) of the normal liver was reduced by 70%, whereas the
      necrotic regions had more than a 50% increase in SI after double contrast. The
      region that was enhanced corresponded largely with the region of necrosis as
      observed postmortem. The lesion size, when identified, was largely underestimated
      using either of the agents along, albeit using the common pulse sequences. The
      double contrast effect of simultaneous administration of gadolinium and
      dysprosium allows accurate delineation of liver necrosis.

PMID- 9170030
TI  - Influence of copper on MRI of hepatocellular carcinoma.
AB  - The purpose of this paper is to clarify whether copper accumulation in
      hepatocellular carcinoma (HCC) is a cause of high intensity signal pattern on T1
      weighted images (T1-WI) by comparing the histologically proven copper
      accumulation with MR images. Forty-five surgically resected HCCs were analyzed.
      Distribution patterns of divalent copper by a modified Timm's method on their
      maximum cut surfaces were compared with signal patterns on corresponding T1-WI.
      The degree of copper accumulation in tumor compared with surrounding liver tissue
      was higher in 6 lesions, equal in 17 lesions, and lower in 22 lesions. High
      intensity pattern on T1-WI were observed in 3 of 6 lesions (50%), 10 of 17
      lesions (59%), and 10 of 22 lesions (45%). Distribution patterns of copper were
      not correlated with intensity patterns on T1-WI. We conclude that the
      paramagnetic effect of divalent copper accumulation in HCC is insufficient to
      influence the MRI.

PMID- 9170031
TI  - Effects of AMI-25 on liver vessels and tumors on T1-weighted turbo-field-echo
      images: implications for tumor characterization.
AB  - This study was devoted to tumor differentiation in liver MR T1-weighted imaging
      with superparamagnetic iron oxide (SPIO). Twenty-one patients with 40 liver
      lesions were studied at 1.5 T. Before and at least 45 minutes after SPIO
      administration, turbo-field-echo (TFE) T1-weighted, TFE T1 x T2*-weighted (MXT),
      and fat-suppressed turbo-spin-echo T2-weighted images were acquired. A
      quantitative analysis was performed blindly. On TFE T1-weighted images, the
      signal enhancement was -33% +/- 12 for the liver, -24% +/- 2 for adenomas and
      focal nodular hyperplasia, +60% +/- 33 for the hemangiomas; metastases and cyst
      enhancement were not significant. After SPIO on TFE T1-weighted images, the
      hemangioma-to-liver signal ratio (149% +/- 18) was definitely higher than the
      mean metastasis-to-liver signal ratio (90% +/- 16). This T1-related
      differentiation ability lacked dramatically on TFE MXT images and, in one case,
      was reduced on post-SPIO TFE T1-weighted images by a long imaging delay after
      SPIO administration (2 hours).

PMID- 9170032
TI  - Assessment of reperfusion injury by means of MR contrast agents in rat liver.
AB  - The purpose of this study was to investigate whether extracellular MR contrast
      agents or intracellular liver-specific MR contrast agents may enable the
      assessment of liver reperfusion injury. Ischemia-related reperfusion was induced
      in 32 rats using Pringle's maneuver. Pringle's maneuver consisted of cross
      clamping of the complete hepatoduodenal ligament for 45 minutes followed by 90
      minutes of reperfusion. Two extracellular (gadopentetate dimeglumine and
      gadobutrol) and two intracellular gadoxetic acid and SH U 555 A) MR contrast
      agents were evaluated as model agents. Control animals and animals with liver
      ischemia were used to calculate changes in liver signal enhancement after
      Pringle's maneuver. Significant changes in liver signal after reperfusion injury
      were observed only with reticuloendothelial system (RES)-specific SH U 555 A.
      Liver signal enhancement after Pringle's maneuver with RES-specific SH U 555 A
      was decreased by 25.4% as compared with the control group. RES-specific contrast
      agents such as SH U 555 A seem to be more sensitive to ischemia-related
      dysfunction of the liver than hepatobiliary contrast agents such as gadoxetic
      acid or extracellular gadolinium chelates at different concentrations because
      Kupffer cells are more sensitive to liver ischemia than hepatocytes.

PMID- 9170033
TI  - Oral administration of a low-cost negative contrast agent: a three-year
      experience in routine practice.
AB  - A low cost, well tolerated, and effective gastrointestinal contrast agent is
      needed for abdominal MRI. The authors tested, in vitro and in routine practice, a
      mixture of 192 g of barium sulfate (Micropaque HD oral, Guerbet, France) diluted
      in 500 ml of gastric antacid (Maalox, Rohrer, Fort Washington, PA). Its T1 and T2
      relaxation times were 324 and 14 msec, respectively (.2 T). This contrast agent
      was used in routine practice in 789 patients (.5 T). It had a low signal
      intensity in 86% and 82% of the cases on T1- and T2-weighted sequences,
      respectively. No side effect due to magnetic susceptibility was seen, even with
      gradient-echo sequences. The dilution of barium sulfate in gastric antacid,
      instead of water, causes a low signal intensity on all sequences for a low barium
      sulfate concentration (38% w/v). This product is an effective and low cost
      contrast agent in routine practice.

PMID- 9170034
TI  - MR multispectral analysis of multiple sclerosis lesions.
AB  - Although quantification of the lesion burden from serial MR examinations of
      patients with multiple sclerosis (MS) is a common technique to assess disease
      activity in clinical trials, pathologic change may occur within a lesion without
      a corresponding change in volume. Therefore, measures of lesion volume and
      composition may improve the sensitivity of detecting disease activity. A new
      technique has been developed that provides information about the intensity
      composition of MS lesions in standard spin-echo MR examinations. The new
      technique is based on the multispectral "feature space" intensity distributions
      of the lesions and normal tissues. Analysis of MR examinations of materials with
      known T1 and T2 times showed that feature space position from spin-echo
      examinations is largely determined from proton density (rho), T2, and the
      interecho delay. Information about intensity composition was obtained by reducing
      the multidimensional intensity distribution to one dimension while minimizing the
      loss of information. This technique was used to analyze eight lesions in standard
      spin-echo MR examinations of three patients with MS. Lesion distributions were
      compared between examinations by first calibrating the examinations based on the
      intensity distributions of cerebrospinal fluid (CSF), an internal reference
      tissue. Many of the lesion distributions had a distinctive peak at low intensity,
      corresponding to normal-appearing white matter (WM). Within the lesion
      distributions, increases in high intensity peaks generally were accompanied by
      reductions in the WM peak. Serial analysis of the lesion distributions revealed
      some dramatic fluctuations, even when lesion volume remained constant.

PMID- 9170035
TI  - High resolution T2-weighted imaging of the human brain using surface coils and an
      analytical reception profile correction.
AB  - High spatial resolution T2-weighted MR images of the human brain were obtained at
      1.5 T. An optimized fast spin-echo (FSE) sequence and 1.5 g/cm gradients were
      used to obtain T2-weighted images in 4 to 9 minutes with an in-plane resolution
      of .27 mm and slice thicknesses from 1.5 to 3 mm. Phased arrays of surface coils
      were used as receivers, providing increased sensitivity but image intensities
      dependent on the reception profile of the coils. This image nonuniformity was
      removed by analyzing the data with a theoretical intensity correction algorithm
      developed in this laboratory. The FSE sequences, the specialized phased arrays of
      surface coils, and the intensity correction algorithm allowed improved
      visualization of nerves within the inner auditory canals and surface anatomy of
      the cerebral cortex. It is expected that this technique will be useful for
      clinical applications that require high resolution imaging of small, superficial
      structures of the brain.

PMID- 9170036
TI  - Evaluation of peri-infarcted hypoperfusion with T2*-weighted dynamic MRI.
AB  - The purpose of this study was to evaluate cerebral perfusion with T2*-weighted
      dynamic MRI in the area around the infarcted core. We examined seven patients
      with subacute cerebral infarction. After bolus injection a gadopentetate
      dimeglumine, a series of gradient-echo images were recorded in a selected slice.
      From these images, concentration-time curves were created on a region-of-interest
      (ROI) basis around infarction for calculating relative regional cerebral blood
      volume (rrCBV). Brain perfusion single photon emission computed tomography
      (SPECT) study also was performed with intravenous injection of 123I-labeled N
      isopropyl-p-iodoamphetamine (123I-IMP). All patients showed prolonged signal
      decrease in the area around the infarcted core. ROI analysis showed significantly
      increased rrCBV compared to the normal side (P < .01, paired t test). The 123I
      IMP SPECT study showed that these areas had decreased cerebral blood flow. Theses
      findings suggest compensatory vascular dilatation due to decreased perfusion
      pressure. T2*-weighted dynamic MRI is a useful method for detecting compensatory
      vasodilatation of ischemic insult in the peri-infarcted area.

PMID- 9170037
TI  - Contrast-to-noise ratio in functional MRI of relative cerebral blood volume with
      sprodiamide injection.
AB  - The purpose of this study was to investigate the dependence of contrast-to-noise
      ratio (CNR) on the dose and rate of sprodiamide injection in magnetic resonance
      relative cerebral blood volume (rCBV) imaging. rCBV maps for 35 normal volunteers
      were constructed from dynamic MR image sets acquired with echo-planar spin-echo
      imaging after intravenous injection of sprodiamide. Doses of .1, .2, and .3
      mmol/kg, at rates of 2 ml/second and 5 ml/second, were tested. CNRs and
      blood/volume ratios of gray to white matter were computed. CNR depended on dose
      (P < .0001) but was independent of injection rate (P < .69). rCBV ratios of gray
      to white matter were dose independent (P < .38) and rate independent (P < .97).
      The dependence of CNR on dose, but not injection rate, has practical implications
      in optimal protocol design. The independence of gray/white ratios supports the
      theory underlying the generation of rCBV maps.

PMID- 9170038
TI  - Signal-to-noise analysis of cerebral blood volume maps from dynamic NMR imaging
      studies.
AB  - The use of cerebral blood volume (CBV) maps generated from dynamic MRI studies
      tracking the bolus passage of paramagnetic contrast agents strongly depends on
      the signal-to-noise ratio (SNR) of the maps. The authors present a semianalytic
      model for the noise in CBV maps and introduce analytic and Monte Carlo techniques
      for determining the effect of experimental parameters and processing strategies
      upon CBV-SNR. CBV-SNR increases as more points are used to estimate the baseline
      signal level. For typical injections, maps made with 10 baseline points have 34%
      more noise than those made with 50 baseline points. For a given peak percentage
      signal drop, an optimum TE can be chosen that, in general, is less than the
      baseline T2. However, because CBV-SNR is relatively insensitive to TE around this
      optimum value, choosing TE approximately equal to T2 does not sacrifice much SNR
      for typical doses of contrast agent. The TR that maximizes spin-echo CBV-SNR
      satisfies TR/T1 approximately equal to 1.26, whereas as short a TR as possible
      should be used to maximize gradient-echo CBV-SNR. In general, CBV-SNR is
      maximized for a given dose of contrast agent by selecting as short an input bolus
      duration as possible. For image SNR exceeding 20-30, the gamma-fitting procedure
      adds little extra noise compared with simple numeric integration. However, for
      noisier input images, can be the case for high resolution echo-planar images, the
      covarying parameters of the gamma-variate fit broaden the distribution of the CBV
      estimate and thereby decrease CBV-SNR. The authors compared the analytic noise
      predicted by their model with that of actual patient data and found that the
      analytic model accounts for roughly 70% of the measured variability of CBV within
      white matter regions of interest.

PMID- 9170039
TI  - Imaging of the lungs using 3He MRI: preliminary clinical experience in 18
      patients with and without lung disease.
AB  - The purpose of this study was to describe the 3He MRI findings of normal
      pulmonary ventilation in healthy volunteers and to evaluate abnormalities in
      patients with different lung diseases. Hyperpolarized 3He gas (300 ml, 3 x 10(5)
      Pa, polarized to 35-45% by optical pumping, provided in special glass cells) was
      inhaled by 8 healthy volunteers and 10 patients with different lung diseases.
      Imaging was performed with a three-dimensional fast low-angle shot (FLASH)
      sequence (TR = 11.8 msec; TE = 5 msec; transmitter amplitude, 5-8 V;
      corresponding flip angle, < 5 degrees) in a single breath-hold (22-42 seconds).
      Clinical and radiological examinations were available for correlation. The
      studies were performed successfully in eight of eight volunteers and in 8 of 10
      patients. The lung parenchyma of volunteers with normal ventilatory function
      exhibited rather homogeneous intermediate to high signal, whereas patients with
      chronic obstructive lung disease or bronchiectasis presented with severe signal
      inhomogeneities with patchy or wedge-shaped defects. The mass effect of
      bronchogenic carcinoma, chronic empyema, lymphadenopathy, or pleural effusion
      caused large signal defects, representing the lesion and adjacent
      hypoventilation, the extent of which had not been presumed from chest x-ray or
      CT. 3He MRI is a promising new modality for the assessment of pulmonary
      ventilation and its abnormalities. Additional studies are needed to determine its
      potential clinical role.

PMID- 9170040
TI  - Relative quantification of pulmonary edema with noncontrast-enhanced MRI.
AB  - Pulmonary edema is a debilitating effect of acute respiratory distress syndrome.
      The ability to measure it noninvasively with high sensitivity and in three
      dimensions could be useful in not only detection but also in assessment and
      guidance of treatment. To this end, a three-dimensional MRI pulse sequence to
      measure the formation of edema was developed and tested. Another sequence was
      tested to measure blood flow in distal pulmonary arteries. Pulmonary edema was
      induced in nine dogs via venous injections of oleic acid. Edema was verified by
      wet-to-dry weight ratio (5.30 +/- .38) and extra-vascular lung water at baseline
      (2.03 +/- 1.12 ml/g dry lung weight) versus postinjury (3.00 +/- 1.45 ml/g) (P <
      .005). The signal-to-noise ratio within the lungs increased from 5.47 +/- 1.00 at
      baseline to 7.51 +/- 1.96 (P < .005), and the time course of edema formation was
      resolved. Results from MR phase-contrast blood flow measurements were variable.
      The authors conclude that the three-dimensional scan provides a sensitive
      relative quantification of pulmonary edema formation without the use of contrast
      agents or ionizing radiation.

PMID- 9170041
TI  - Optimization of contrast timing for breath-hold three-dimensional MR angiography.
AB  - The purpose of this study was to determine the influence of various factors (age,
      weight, breathing, saline flush) on the contrast kinetics of a test bolus
      injection for the purpose of calculating the scan delay for optimized contrast
      enhanced three-dimensional MR angiography. Initially, the test bolus
      administration was optimized by evaluating the influence of breathing (breathing
      versus breath-hold) and the administration of a saline flush after the contrast
      injection (no flush versus flush) on the kinetics of a 4-ml Gd-DTPA test bolus
      injection in three healthy volunteers. Subsequently, in 33 patients referred for
      three-dimensional MR angiography of the renal arteries, test bolus kinetics were
      correlated to age, weight, and heart rate. In addition, the image quality of the
      three-dimensional MR angiograms was assessed on a four-point scale with regard to
      vessel visibility. The administration of a saline flush after the contrast
      injection significantly shortened the first appearance time (14 versus 16
      seconds, P < .05), as well as the time to maximal signal intensity (SI) (6 versus
      10 seconds, P < .05) and increased both maximum (67 versus 151 seconds, P < .05)
      and the SI slope (6.4 versus 20.5 seconds, P < .05). Breath-holding was shown to
      have no significant affect on the test bolus kinetics. No correlation was found
      between physiologic parameters and test bolus kinetics in the patient group.
      Image quality was graded as sufficient for diagnostic purposes in 32 of 33
      patients. The contrast travel time from injection site to the vascular system
      under consideration cannot be predicted based on physiologic parameters. This
      time interval can be reliably and accurately determined by a test bolus injection
      of a small volume of contrast agent followed by a saline flush during normal
      breathing.

PMID- 9170042
TI  - Measurement of collateral blood flow in a porcine model of aortic coarctation by
      velocity-encoded cine MRI.
AB  - The purpose of this study was to investigate the time course of development of
      collateral blood flow in an animal model of aortic coarctation. A juxtaductal
      aortic stenosis (model coarctation) was surgically created in five juvenile pigs.
      MRI was performed preoperatively, 1 to 2 days postoperatively, and 2 to 10 weeks
      postoperatively. Aortic blood flow was measured by velocity-encoded cine MR (VENC
      MR). The percent change in aortic blood flow (delta BF) from proximal to distal
      descending thoracic aorta was calculated, and a multiple-comparison paired t test
      used to assess changes in delta BF over time. Invasive flow measurements were
      obtained in one animal before sacrifice using an ultrasonic probe. delta BF
      preoperatively was -2 +/- 8% (mean +/- SE). delta BF increased to 32 +/- 7% (mean
      +/- SE, P = .022) 2 days postoperatively and 55 +/- 19% (P = .032) 2 to 8 weeks
      postoperatively. Invasive measurements were in qualitative agreement with the
      VENC-MR data. VENC-MR is an accurate noninvasive method of measuring collateral
      blood flow in aortic coarctation. Recruitment and development of collateral flow
      pathways occur rapidly in an animal model.

PMID- 9170043
TI  - Probing tumor microvascularity by measurement, analysis and display of contrast
      agent uptake kinetics.
AB  - This paper describes a measurement protocol for acquiring quantitative dynamic
      MRI data and novel analysis and display software (Magnetic Resonance Imaging
      Workbench (MRIW)). Proton density-weighted and T1-weighted two-dimensional
      gradient echo images are used to quantify tissue contrast agent concentration.
      The dynamic studies last approximately 7 minutes, with 10-second temporal
      resolution. Analyses of signal and concentration changes with time are performed,
      allowing capillary permeability-surface area product, tissue leakage space,
      enhancement onset time, mean enhancement gradient and maximum enhancement level
      to be mapped as false-color parametric overlays registered with anatomic images.
      Quantification of permeability and leakage space provides a method for comparing
      physiology in patients between visits or for intersite comparisons.

PMID- 9170044
TI  - Contrast enhancement pattern and frequency of previously unoperated lumbar discs
      on MRI.
AB  - Enhancement frequency and patterns (linear intradiscal, nodular intradiscal, and
      peridiscal) of the 210 previously unoperated lumbar discs were evaluated using
      contrast-enhanced lumbar MRI. They also were compared with morphologic
      abnormalities (normal, bulging, protruded, and extruded) and signal alteration
      (high signal on T2-weighted images) of the disc. Image interpretation was decided
      by the consensus of two musculoskeletal radiologists. Enhancement was observed in
      69 (32.6%) discs. The enhancement patterns were either intradiscal, linear of
      (79.7%) or nodular (10.2%), peridiscal (7.2%), or combined (2.9%). Thirty-five
      (77.8%) of the 45 herniated discs, 35 (77.8%) were enhanced, whereas 34 (20.6%)
      of 165 normal-appearing disc were enhanced. Enhancement was observed more
      frequently in discs with high signal intensity zones (P < 0.05). In the six
      patients with enhanced discs, surgery revealed granulation tissue in three
      extruded discs, two protruded discs, and one bulging disc. The authors believe
      that contrast enhancements are frequent in herniated discs and are not infrequent
      in normal-appearing discs. The understanding of various enhancement patterns may
      help in the interpretation of lumbar spine MRI.

PMID- 9170045
TI  - Evaluation of an ultrasmall superparamagnetic iron oxide in MRI in a bone tumor
      model in rabbits.
AB  - Ultrasmall superparamagnetic iron oxides (USPIOs) are a class of MRI contrast
      agents having moderately selective affinity for the reticuloendothelial cells of
      lymph nodes and bone marrow. This study evaluated a USPIO preparation, Combidex
      (Code 7227), in MRI of a rabbit bone tumor model. VX2 carcinoma implanted into
      the tibial marrow of nine subject rabbits was studied. After tumor growth, the
      subjects underwent MRI of their lesions both before and after intravenous
      administration of Code 7227. Code 7227 was judged subjectively to conspicuously
      reduce the signal intensity of normal marrow on some pulse sequences. A
      hypointense zone outlined the tumor margins on postcontrast imaging, which
      allowed improved visualization of the soft tissue component of the larger
      lesions. Accumulation of the contrast agent in a zone of inflammation outside the
      tumor margin was demonstrated on histologic sections of the lesions. Code 7227
      deserves additional study as a potential contrast agent for MRI of bone tumors.

PMID- 9170046
TI  - Fat-saturated contrast-enhanced T1-weighted MRI in evaluation of osteosarcoma and
      Ewing sarcoma.
AB  - To assess contrast-enhanced (C+), fat-saturated (FatSat), T1-weighted (T1W)
      imaging in the characterization of the soft tissue mass associated with primary
      bone tumors, we compared it with T2-weighted (T2W) imaging in patients with
      osteosarcoma (n = 36) and Ewing sarcoma family of tumors (Ewing sarcoma; n = 11).
      Periosseous tumor compared with normal muscle had greater contrast-to-noise ratio
      (CNR) on the FatSat T1W C+ image than on T2W for 81% (38/47; P < .0001) of
      patients. The CNR of periosseous tumor compared with subcutaneous fat was greater
      on FatSat T1W C+ for 98% (46/47; P < .0001). Radiologists found it easier to
      evaluate neurovascular bundle proximity to tumor with FatSat T1W C+ images than
      with T2W for 64% of patients (30/47; P < .0001). They judged FatSat T1W C+
      superior to T2W for periosseous tumor conspicuity and visualization of soft
      tissue necrosis in 62% (29/47; P < .0001). In patients with osteosarcoma or Ewing
      sarcoma, FatSat T1W C+ imaging may replace T2W imaging for soft tissue mass
      evaluation, especially if contrast is being used for dynamic enhancement.

PMID- 9170047
TI  - Triangular fibrocartilage and intercarpal ligaments of the wrist: does MR
      arthrography improve standard MRI?
AB  - The objective of this study was to assess the value of adding MR arthrography to
      standard MRI for patients with chronic wrist disorders. Thirty consecutive
      patients (age range, 19-73 years; mean, 36.2 years) were included in the
      investigation. The images were evaluated blindly and separately by two
      radiologists with regard to lesions of the scapholunate (SL) and lunotriquetral
      (LT) ligaments and the triangular fibrocartilage (TFC). Conventional two- or
      three-compartment arthrography was used as the standard of reference. For TFC
      lesions, standard MR images had a sensitivity of 92.3% (reader 1) and 84.6%
      (reader 2) and a specificity of 41.2% (reader 1) and 52.9% (reader 2). For MR
      arthrography, sensitivity was 84.6% (reader 1) and 84.6% (reader 2) and
      specificity was 88.2% (reader 1) and 100% (reader 2). For SL ligament tears,
      standard MRI had a sensitivity of 33.3% (reader 1) and 11.1% (reader 2) and a
      specificity of 47.6% (reader 1) and 57.1% (reader 2). For MR arthrography,
      sensitivity was 66.7% (reader 1) and 55.6% (reader 2) and specificity was 52.4%
      (reader 1) and 81.0% (reader 2). For LT ligament tears, standard MRI had a
      sensitivity of 28.6% (reader 1) and 35.7% (reader 2) and a specificity of 93.8%
      (reader 1) and 81.3% (reader 2). For MR arthrography, sensitivity was 35.7%
      (reader 1) and 23.1% (reader 2) and specificity was 93.8% (reader 1) and 94.1%
      (reader 2). In conclusion, the diagnostic performance of MRI in suspected lesions
      of the TFC and the SL and LT ligaments is improved by adding MR arthrography to
      the standard examination.

PMID- 9170048
TI  - Breath-holding in healthy and pulmonary-compromised populations: effects of
      hyperventilation and oxygen inspiration.
AB  - Suspension of respiration during end-expiration often is recommended to minimize
      body organ displacement between sequential image acquisitions. The purpose of
      this report is to evaluate techniques for end-expiratory breath-holding
      applicable to a pulmonary-compromised population. Eighty-seven consecutive
      outpatients with chronic pulmonary diseases and 31 healthy nonsmoking volunteers
      were recruited for the study. All subjects were asked to hold their breath in end
      expiration while in the supine position (29 after breathing room air, 29 after
      hyperventilating room air for six breaths, and 29 after breathing O2 from a
      portable oxygen tank via nasal cannula until pulse-oximeter readings stabilized
      or reached 100%). Each volunteer was tested with all three methods. The mean
      length of time for a breath-hole on room air without hyperventilation was 9.2
      seconds for the patients and 31.7 seconds for the volunteers. A breath-hold after
      hyperventilation of room air was timed at 12.3 seconds for the patients and 41.2
      seconds for the volunteers, and after O2 administration, the breath-hold was 22.4
      seconds for the patients and 60.9 seconds for the volunteers. No adverse effects
      occurred. The pulmonary-compromised patient can suspend respiration most
      successfully after O2 administration (P < .0001), whereas hyperventilation seems
      to be less beneficial. Nonpulmonary-compromised volunteers can hold their breath
      for longer periods of time.

PMID- 9170049
TI  - Thoracic outlet syndrome in a throwing athlete diagnosed with MRI and MRA.
AB  - Thoracic outlet syndrome comprises the clinical manifestations in the arm caused
      by compression of the neurovascular bundle as it leaves the thoracic inlet. The
      neurovascular bundle is composed of the subclavian artery, the subclavian vein,
      and the brachial plexus. The symptoms of thoracic outlet or inlet syndrome are
      most often caused by compression of the nerves of the brachial plexus, which is
      involved in up to 98% of cases; the remainder are due to vascular compression.
      MRI with MRA demonstrates well the anatomy of the brachial plexus as well as any
      vascular compression or occlusion. The relationship of the axillary and
      subclavian vein to the first rib and subclavius muscle also can be demonstrated.
      We present a college baseball player who presented with numbness in the fingers
      of his throwing hand when throwing a baseball. Evaluation with spin-echo and two
      dimensional time-of-flight MR angiographic (MRA) imaging of the thoracic outlet
      region revealed obstruction of the subclavian vein with the arm abducted. To our
      knowledge, no such cases have been diagnosed previously with MRI.

PMID- 9170051
TI  - Multibolus stimulated echo imaging of coronary artery flow.
AB  - One limitation of traditional bolus tagging techniques for MR angiography is the
      small amount of blood labeled by one tagging, resulting in a limited filling of
      the downstream vessels. We describe a multiple bolus technique using stimulated
      echoes (STE) for imaging coronary flow. A series of radiofrequency (RF) pairs are
      given with each pair selective at the region of tagging, thus tagging consecutive
      volumes of blood, and a final nonselective pulse is given to "read out" all of
      the tagged spins. In this way, multiple boluses of tagged blood are imaged at one
      time.

PMID- 9170050
TI  - Three-dimensional reconstruction of the liver venous system using the
      preservation solution as contrast agent.
AB  - To investigate whether MRI without using artificial contrast agents can provide
      sufficient image contrast to visualize the venous tree in the cold stored liver
      graft, two pig liver grafts were scanned with a multislice turbo spin-echo
      sequence with long TE (200 msec). The quality of the data obtained at 1-T field
      strength was sufficient for three-dimensional reconstruction of the hepatic
      vascular system, potentially useful for liver splitting surgery.

PMID- 9170052
TI  - MRI acoustic noise: sound pressure and frequency analysis.
AB  - The large gradient coils used in MRI generate, simultaneously with the pulsed
      radiofrequency (RF) wave, acoustic noise of high intensity that has raised
      concern regarding hearing safety. The sound pressure levels (SPLs) and power
      spectra of MRI acoustic noise were measured at the position of the human head in
      the isocenter of five MRI systems and with 10 different pulse sequences used in
      clinical MR scanning. Each protocol, including magnetization-prepared rapid
      gradient echo (MP-RAGE; 113 dB SPL linear), fast gradient echo turbo (114 dB SPL
      linear), and spin echo T1/2 mm (117 dB SPL linear), was found to have the high
      SPLs, rapid pulse rates, amplitude-modulated pulse envelopes, and multipeaked
      spectra. Since thickness and SPL were inversely related, the T1-weighted images
      generated more intense acoustic noise than the proton-dense T2-weighted measures.
      The unfiltered linear peak values provided more accurate measurements of the SPL
      and spectral content of the MRI acoustic noise than the commonly used dB A
      weighted scale, which filters out the predominant low frequency components.
      Fourier analysis revealed predominantly low frequency energy peaks ranging from
      .05 to approximately 1 kHz, with a steep high frequency cutoff for each pulse
      sequence. Ear protectors of known attenuation ratings are recommended for all
      patients during MRI testing.

PMID- 9170053
TI  - MRI-compatible cardiac pacing catheter.

PMID- 9170054
TI  - Female psychology in progress.

PMID- 9170055
TI  - Female psychology: an introduction.

PMID- 9170056
TI  - Freud and feminine subjectivity.
AB  - I have delineated a factor, subjectivity, to account for the difficulty in the
      psychoanalytic understanding of feminine sexuality, particularly the nature of
      feminine sexual pleasure. This factor has been unappreciated hitherto by
      psychoanalysts. Subjectivity is a notion that refers to the capacity of a person
      to posit him- or herself as an independent agent who determines or controls his
      or her own thoughts and actions. The construct feminine sexual pleasure, and by
      extension feminine subjectivity, was difficult for Freud and others to posit
      because of the implicit association among several mental phenomena. Subject,
      active, and libido (i.e., the source of active sexual pleasure) were, and to some
      extent still are, considered masculine attributes; whereas object, passive, and,
      by implication, the absence of an independent actively desirous state were
      considered feminine attributes. Freud's difficulty in accepting aggression in the
      mental life of women interfered with his gaining an implicit understanding of
      feminine subjectivity.

PMID- 9170057
TI  - Freud and the repudiation of the feminine.
AB  - This paper begins with a discussion of Freud's central ideas on the feminine in
      his landmark paper, Female Sexuality (1931), written within months after his
      mother's death. It then traces the evolution of these ideas from the perspective
      of his own history from childhood to old age. Using some of his letters and
      clinical papers as reference, one sees that his experience of the feminine in
      himself, and especially his repudiation of the female components of his own
      identity, contributed to his belief that such repudiation of the feminine in
      males was a universal, biologically rooted phenomenon. His personal evolution,
      enriched by self-analytical insights, is reflected in changes in the nature of
      his understanding of, and in his ability to accept, his women patients'
      representations of him as feminine and maternal.

PMID- 9170058
TI  - Feminist psychoanalytic theory: American and French reactions to Freud.
AB  - Ever since Freud's observations on women and their psychology were published,
      there have been revisions, expansions, and reactions to his ideas. Most recently,
      feminist psychoanalytic theorists from the United States and France have been
      fertile in producing revisions to traditional psychoanalytic theory about women.
      Reviewing the disjointed psychoanalytic traditions of the two countries provides
      a context for understanding the different approaches to feminist thinking that
      each country has produced. American feminist psychoanalytic theorists tend to
      stage reversals of traditional Freudian theory, while the French feminist
      psychoanalytic theorists have had to position themselves intellectually and
      politically with reference to the teachings of Lacan. This paper examines
      selected contemporary theorists from these two countries--Jean Baker Miller,
      Nancy Chodorow, and Carol Gilligan from the United States and Julia Kristeva,
      Luce Irigaray, and Helene Cixous from France--and discusses the difficulties of
      constructing a theory of sexual difference that avoids the pitfalls of either
      biological essentialism or its reverse, social constructionism.

PMID- 9170059
TI  - Nature, nurture, and core gender identity.
AB  - Literature about gender differences and their possible origins, and contemporary
      psychoanalytic formulations of gender, is reviewed. There is a broad consensus
      among investigators from different fields, and among psychoanalysts of different
      theoretical persuasions, that the modal female personality tends to be more
      sociocentric, and the modal male personality more self-centric. These modal
      personality differences may be qualitative rather than quantitative. The concept
      of core gender identity, which articulates the psychological root of these
      differences, is reexamined in the light of contemporary research into
      constitutional differences in the organization and activation of the brain, and
      an interactional model of core gender identity as a dynamic evolving phenomenon
      over the course of the life cycle is proposed.

PMID- 9170060
TI  - Unconscious representation of femininity.
AB  - This paper sets out some of the main differences in approaches to the study of
      female sexuality, in particular in terms of the place of the body and biology in
      the construction of femininity. It illustrates a dual aspect of femininity in its
      reference to lack and in its more immediate bodily reality, suggesting that it is
      the interplay of these two which traces a woman's sexual position.

PMID- 9170061
TI  - A reconsideration of object choice in women: phallus or fallacy.
AB  - Within the context of Freud's theory of instinctual drives, analytic data from
      three female patients are presented which refute his concept that penis envy is
      the basis for female object choice. Contrary to Freud's theory, these patients
      did not feel their genitalia or genital arousal were inadequate. Rather, they
      believed their genital sexuality and fantasies were powerful and gratifying, but
      dangerous and bad. Their subsequent guilt and fears led secondarily to their
      defensive wish to have a penis to avoid their core conflicts; their penis envy
      was pathological. The data unequivocally demonstrate that the clitoris is not an
      inferior organ, but is the locus for the initiation of intense pleasure and
      occasional orgasm as early as ages four to six, when vaginal awareness also is
      present. In addition the material provides evidence that girls choose fathers to
      feel loved and valued, and that their wish for a baby is not a substitute for a
      relinquished wish for a penis. Observational studies and a vignette suggest that
      the instinctual drives of the genital phase coalesce with a change in object
      relations, forming an important motivation for a girl to switch her primary love
      object from her mother to her father.

PMID- 9170062
TI  - Beyond the he and the she: toward the reconciliation of masculinity and
      femininity in the postoedipal female mind.
AB  - This paper concerns a postoedipal psyche organization in the female mind whereby
      early overinclusive body-ego representations and cross-sex identifications are
      recuperated symbolically in the context of a differentiated female identity. This
      reintegration allows the female to symbolize what has been "lost" upon awareness
      of sex differences, play out masculine aspects without there being a threat to
      her core, primary feminine identity, and by linking rather than prohibiting cross
      gender representations, provide imaginative elaboration and empathic access to
      another as a subject. This state does not reflect a denial of difference; rather,
      it reflects a psychic organization that uses symbolization to play with
      differences. Bisexual conflict can be mastered rather than repressed. Such
      mastery transcends normative, rigid, polarized sexual positions and gender
      conformity, perversions, and disturbed gender identity. Within the classical
      discourse, this mastery is suggested as an expansion of our limited and archaic
      notions of a genital stage specifically for the female. A new elaboration of a
      specific female genital stage can deepen our understanding of adult femininity
      and the development of cross-gender transference.

PMID- 9170063
TI  - From "nothing" to "something" to "everything": bisexuality and metaphors of the
      mind.
AB  - Psychoanalytic understanding of female sexuality has continued to evolve since
      Freud presented it as a central and abiding question in psychoanalytic theory.
      This paper is an attempt to demonstrate that much of what we have learned and
      added to our theory is based in part on the classical thinking which remains a
      foundation of psychoanalytic wisdom about human sexuality in general, male and
      female. And this foundation rests on the cornerstone of the human longing for
      completeness, for "everything"--a bisexual core. A clinical case, the basis of
      psychoanalytic data, demonstrates, primarily through the analysis of a dream, the
      neurotic derailments that follow upon a disavowal of the need for the little girl
      to identify with the metaphorical representation of male genitalia. The
      theoretical underpinnings of this perspective are presented as well as a
      correction of a common misreading of Freud's ideas about anatomical "bedrock."

PMID- 9170064
TI  - Theoretical gender and clinical gender: epistemological reflections on the
      psychology of women.
AB  - This paper points to problematic tendencies in psychoanalytic thinking about
      women and suggests approaches that might address these problems. Psychoanalytic
      theories about women tend to overgeneralize, universalize, and essentialize.
      Furthermore, they do not sufficiently explicate the inextricable cultural aspects
      in anyone's gender psychology, and they are often permeated with unreflected-upon
      cultural assumptions. I suggest that paying attention to clinical individuality
      and assuming that subjective gender has multiple components for everyone gives us
      better understanding of our patients and points us toward more accurate and
      complete gender theories. There are many psychologies of women. Each woman
      creates her own psychological gender through emotionally and conflictually
      charged unconscious fantasies that help construct her inner world, that
      projectively imbue cultural conceptions, and that interpret her sexual anatomy.
      By making some unconscious fantasies and interpretations more salient than
      others, each woman creates her own prevalent animation of gender.

PMID- 9170065
TI  - The meaning of perineal activity to women: an inner sphinx.
AB  - This paper is an inquiry into the close association of anal and genital functions
      in women and the background and meaning of that association. Excerpts from the
      analyses of two women with sexual and intellectual inhibitions illustrate aspects
      of erotic life deriving from anal-phase development, and the unconscious fantasy
      of an inner, erotic, and powerful "organ." Along with the lifting of their
      inhibitions, both analysands achieved integration of anal-sadistic and
      incorporative wishes with vaginal receptivity. Female anatomy and physiology are
      so arranged that the action of perineal and sphincter musculature also stimulates
      the genital. This fosters overlapping mental representations of vagina and rectum
      which in turn affect body image and unconscious fantasy in women. The experience
      of perineal contraction acquires complex psychic meanings with both libidinal and
      aggressive charge. The libidinal aspect is the largely covert erotic sensation
      that informs the mental representation of the genital and is destined to be
      integrated into female sexuality. The aggressive component may present as an
      unconscious fantasy of possessing an inner, powerful, and dangerous organ--a
      focus for conflict between anal-sadistic wishes and early elements of the
      superego.

PMID- 9170066
TI  - Primary femininity and female genital anxiety.
AB  - Primary femininity implies that female development proceeds along lines that
      generate anxiety about damage and loss similar to the fears of castration that
      trouble males. The female fears are classified as fear of painful penetration,
      fear of loss of pleasure, and fear of loss of procreative function. The first two
      fears are illustrated with clinical material showing the ways in which they
      manifest themselves in adult women.

PMID- 9170067
TI  - Castration anxiety or feminine genital anxiety?
AB  - Adherence to terminology that no longer reflects current theories of female
      development is explored and challenged. In particular, the concepts of castration
      anxiety and phallic phase are examined and an argument is made for the general
      usage of the terms, feminine genital anxiety and infantile genital phase.
      Relevant literature is reviewed and a case is presented to illustrate the
      concepts. Speculations are offered as to why we persist in keeping woman a "dark
      continent."

PMID- 9170069
TI  - Masturbation fantasies in a prelatency girl: early female body fantasy conflicts
      as a major determinant in the experience of primary femininity.
AB  - Material from a child-analytic case is presented demonstrating the way in which a
      girl created erotic fantasies from her understanding of bodily sensations and
      used those fantasies in masturbation. The material shows how analysis of early
      fantasies of this nature helps us to understand and follow a line of development
      of primary femininity in which core conflicts involving urethral sphincter,
      periurethral, and bladder sensations combine with genital area sensations in the
      creation of anxiety over fears of genital injury. The clinical implication of
      anxiety as the dominant affect early in female development in this case is
      discussed.

PMID- 9170068
TI  - Nevermore: the hymen and the loss of virginity.
AB  - A major milestone in a woman's life is the loss of virginity, "defloration," with
      the breaking of the hymen. Psychoanalysis has paid little attention to the
      meaning of defloration to either women or men, and virtually none to the hymen as
      a part of the female genitalia. The reasons for this disregard or avoidance are
      explored. Utilizing the few psychoanalytic writings, mythology, literature, and
      anthropological studies in addition to numerous clinical examples, the authors
      find that the unconscious meanings of the loss of virginity and the hymen emerge
      clearly. The common theme is that of negation, never, never again, never seen,
      known or named. Theoretical considerations regarding female sexuality are
      discussed. Technical implications for analyst-patient are presented.

PMID- 9170070
TI  - A revised psychoanalytic view of menopause.
AB  - The traditional psychoanalytic view of menopause regards it as inevitably
      accompanied by reactive depression resulting from the loss of reproductive
      function. This view is grounded on a theory of female sexual development that
      stresses the centrality of the phallic castration complex. The inevitable
      menopausal depression involves a remobilization of this complex and a
      reexperiencing of castration fears. The new view, based on the concept of primary
      feminine identity, complements the concept of a phallic castration complex with
      the related concept of female castration anxiety. In this view menopause, though
      it typically involves physical discomfort and a reworking of maternal
      identification, involves an interplay of both types of castration fears. By
      understanding and analyzing these fears, progressive adaptation to menopause,
      including the opportunity for enhanced creativity and emotional fulfillment, is
      possible. A clinical case example is presented to illustrate these ideas.

PMID- 9170071
TI  - Pregnancy--procreative process, the "placental paradigm," and perinatal therapy.
AB  - Based on extensive clinical experience with childbearing women, a metaphor is
      suggested depicting psychic reality during pregnancy as a "procreative
      container," constituted through three intertwining systems--physiological
      placental, intrapsychic-familial and socioenvironmental. Psychohistorically
      predisposed thresholds of tolerance are proposed, with each woman manifesting
      varying degrees of "permeability" or "psychological immunity" to engagement in
      the process of emotional gestation. A model illustrates variations in affective
      quality, fixity, and intensity of preconscious maternal representations
      underpinning defensive structures. This "placental paradigm" charts seven
      permutations of the combination of herself as mother to her fantasized baby (in
      relation to split aspects of herself as baby to her archaic mother) and effects
      of these imagined dyads on the postnatal exchange. The paper concludes with an
      exposition of unique features of psychoanalytic treatment during pregnancy and
      postnatally, and the impact of the procreative psychic reality on patient and
      analyst.

PMID- 9170072
TI  - The pregnant mother and the body image of the daughter.
AB  - This paper is about the place of the pregnant maternal body in the developing
      body image of the daughter. Adult examples from two cases are offered to
      demonstrate its lingering effects on the women's perceptions of their shapes,
      sizes, abdomens, breasts, and buttocks. Attention is drawn to its neglect in our
      formulations. It is suggested that the whole exterior of the body of the female
      is as important to her as the outer and inner genitals, and makes a vital
      contribution to the final shape of her gender role identity.

PMID- 9170073
TI  - On motherhood.
AB  - In working with mothers' responses to the total or partial loss of their child,
      it becomes evident that, at one level, they experience such a loss as an injury
      to the integrity of their body ego, which includes the child. Their capacity to
      invest the child as a bodily part of themselves as well as to release him and
      transfer bodily ownership to him in the course of personality growth necessitates
      flexible body boundaries. This characteristic of the female body ego is both
      gratifying and threatening to the mother as well as to others. It also has a
      profound impact on the growing boy's and girl's attempts to differentiate
      themselves from the mother bodily and to delineate their own sex-specific body
      ego. The nature and outcome of this difficult process has a significant effect on
      women's and men's attitudes to motherhood. These attitudes contain many defensive
      measures against the primitive anxieties of this early level, contributing
      perhaps also to the frequent neglect of motherhood in theories of female
      psychology.

PMID- 9170074
TI  - Two women and their mothers: on the internalization and development of mother
      daughter relationships.
AB  - This is a report from a 30-year followup study conducted by a member of Margaret
      Mahler's original separation-individuation research team. Based on a series of
      unstructured, clinical interviews with the original subjects and psychological
      testing of the subjects and their mothers, two mother-daughter pairs are compared
      from the perspective of the meaning of each daughter to her mother, how that
      meaning influenced the separation-individuation process, and how it influenced
      the unfolding of each daughter's life as a woman. Because the mother-child pairs
      were observed several times a week by both participant and nonparticipant
      observers beginning during the preverbal period, this study offers a unique
      opportunity to examine the influence of the earliest interactions on adult life.

PMID- 9170075
TI  - Toward further analytic understanding of lesbian patients.
AB  - Psychoanalytic understanding of lesbianism has been excessively welded to unitary
      dynamic and etiologic themes, while actual dynamics vary among lesbian patients.
      Clinical material will illustrate this variety. Limitations in past theories and
      countertransference issues will be discussed. It is proposed that dynamics in
      lesbian patients should not be confused with pathology, and that an object choice
      originally embedded in conflict can become secondarily autonomous or remain
      fluid.

PMID- 9170076
TI  - Hearing what cannot be seen: a psychoanalytic research group's inquiry into
      female sexuality.
AB  - Advances in the theoretical understanding of female psychology are not easily
      integrated into psychoanalytic practice. This paper reports on a study of female
      psychology and clinical practice by a group of seven female psychoanalysts.
      Through discussing the literature and case vignettes, we discovered a lag between
      current theoretical ideas and our clinical practice. The group identified an
      anachronistic emphasis on penis envy functioning as "bedrock." This report
      addresses how the group facilitated individual members' integration of theory and
      practice, and how this integration affected work with patients. We found that as
      we became open to considering a wider range of potential dynamic meanings of
      penis envy and female bodily concerns, we were able to explore a richer, and
      often surprising unfolding of vicissitudes. The discussion highlights some
      technical issues with this approach.

PMID- 9170078
TI  - A food safety system ... from embryo to maturity.

PMID- 9170077
TI  - Can we be both women and analysts?
AB  - The authors, candidates at a psychoanalytic institute that has not had a woman
      training analyst for more than 20 years, have a unique vantage point from which
      to examine the woman's development as an adult female and as a psychoanalyst. Our
      group has engaged in a series of discussions asking: Can we be both women and
      analysts? Comparing and contrasting our experiences with feedback from colleagues
      across the United States and abroad, we had to accept that our unique situation
      could not be a foil for the training dilemmas facing women. Our insights into the
      challenges involved with training, expression of sexuality, family ties,
      formation of an analytic identity, creative contributions to the field, and
      career progression have caused us to arrive at some sobering observations and
      hard-hitting questions which we present here. We hope that as we describe our
      discussions about the woman analyst's experience an active dialogue will arise
      within the reader's mind, and subsequently with colleagues.

PMID- 9170080
TI  - Mississippi State clarifies its curriculum.

PMID- 9170081
TI  - United States should export knowledge.

PMID- 9170082
TI  - Possible problems in measuring nitric oxide.

PMID- 9170084
TI  - Impact of the Animal Drug Availability Act on veterinary practitioners and the
      animal health industry.

PMID- 9170083
TI  - Evaluation of a practice-based ambulatory program in food animal medicine,
      surgery, and herd health management.
AB  - OBJECTIVE: To assess the educational value of a practice-based ambulatory program
      used at a school of veterinary medicine. DESIGN: Retrospective cohort study.
      SAMPLE POPULATION: Graduates of US veterinary medical schools between 1987 and
      1994. PROCEDURE: Phase I involved use of interviews and focus groups to assist in
      development of the questionnaire used in phase II, a retrospective cohort study.
      The pretested questionnaire was sent to a study population consisting of all
      graduates of the University of Wisconsin-Madison, School of Veterinary Medicine,
      between 1987 and 1994 as well as a control group who were randomly selected from
      the 1994 AVMA list of veterinarians. Control-group veterinarians were matched on
      the basis of professional activity, region, and year of graduation. RESULTS: 728
      of 1,067 veterinarians completed the questionnaire in phase II of the study
      (response rate, 68%). The practice-based ambulatory program at the University of
      Wisconsin-Madison compared favorably with university-based ambulatory programs in
      volume of experiences and perceived educational quality. Regardless of rotation
      type, female students were significantly less likely to observe or perform 12
      specific clinical procedures and were significantly less likely to rate
      instructional quality as excellent or very good, compared with male students.
      CLINICAL IMPLICATIONS: Practice-based ambulatory rotations can be a good
      alternative to existing university-based ambulatory rotations. Implementation of
      these programs should emphasize performance of procedures while striving to
      ensure participation of female students.

PMID- 9170085
TI  - What is your diagnosis? Ruptured bladder with uroperitoneum.

PMID- 9170086
TI  - Grounds for recovery and defenses in feed liability cases.

PMID- 9170087
TI  - Organisms isolated from dogs and cats with anaerobic infections and
      susceptibility to selected antimicrobial agents.
AB  - OBJECTIVE: To determine the prevalence of obligate anaerobic bacteria in
      bacterial infections in dogs and cats and susceptibility to selected
      antimicrobial agents. DESIGN: Case series. SAMPLE POPULATION: Specimens from
      1,267 dogs and 243 cats. PROCEDURE: Standard anaerobic and aerobic bacterial
      culture methods were used. Anaerobic isolates were tested for susceptibility to
      selected antimicrobial agents. RESULTS: Obligate anaerobic bacteria were isolated
      from 199 (15.7%) and 69 (28.4%) specimens obtained from dogs and cats,
      respectively. More than half of the specimens that contained obligate anaerobic
      bacteria were from draining tracts (exclusively dogs), pleural fluid, abscesses,
      bones, the respiratory tract, or the abdominal cavity. The most commonly isolated
      obligate anaerobic bacteria (approx 70% of all isolates) were Bacteroides spp,
      Peptostreptococcus spp, Fusobacterium spp, and Porphyromonas spp. Eighty percent
      of the specimens that contained obligate anaerobic bacteria also contained
      facultative anaerobic or aerobic organisms. The organisms most commonly isolated
      in association with obligate anaerobic bacteria were members of the family
      Enterobacteriaceae (Escherichia coli was the most common), Pasteurella spp, and
      Staphylococcus intermedius. Ninety-seven obligate anaerobic isolates were tested
      for susceptibility to ampicillin, amoxicillin-clavulanic acid, chloramphenicol,
      clindamycin, and metronidazole. All were susceptible to amoxicillin-clavulanic
      acid and chloramphenicol, and most were susceptible to metronidazole. Only 71% of
      the Bacteroides isolates were susceptible to ampicillin, and only 83% were
      susceptible to clindamycin. Only 80% of the Clostridium isolates were susceptible
      to clindamycin, but all were susceptible to ampicillin. CLINICAL IMPLICATIONS:
      Data on sites and conditions from which anaerobic bacteria are commonly isolated,
      along with results of susceptibility testing, may be useful in designing
      antimicrobial treatment regimens.

PMID- 9170088
TI  - Effect of racing on serum sodium and potassium concentrations and acid-base
      status of Alaskan sled dogs.
AB  - OBJECTIVE: To examine the effect of participation in a long-distance race on
      serum electrolyte concentrations, estimated exchangeable cation content, and acid
      base status of Alaskan sled dogs. DESIGN: Prospective study. ANIMALS: 9 male and
      5 female, sexually intact, physically fit Alaska sled dogs between 18 and 48
      months old. PROCEDURE: Body weight was recorded, and blood samples were collected
      from dogs before, during, and after a 300-mile race. RESULTS: Serum sodium and
      potassium concentrations decreased during the race, as did serum total protein,
      albumin, and globulin concentrations and PCV. Effects on acid-base status were
      minimal. Body weight and estimated total exchangeable cation content in dogs also
      decreased significantly during the race. CLINICAL IMPLICATIONS: Prolonged running
      is associated with decreases in serum cation concentration and estimated total
      exchangeable cation content in dogs, as in human beings and horses. However, the
      mechanism of the decrease in serum cation concentration likely differs among
      species. Clinical abnormalities associated with cation depletion were not
      observed in the dogs in this study.

PMID- 9170090
TI  - Intravenous administration of human immune globulin in dogs with immune-mediated
      hemolytic anemia.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous administration of
      human immune globulin in the treatment of dogs with immune-mediated hemolytic
      anemia (IMHA). DESIGN: Prospective clinical trial. ANIMALS: 10 dogs with
      confirmed primary IMHA that had failed to respond to conventional
      immunosuppressive treatment (administration of prednisone and cyclophosphamide or
      azathioprine). PROCEDURE: Diagnosis of IMHA was confirmed by detecting
      spherocytosis or autoagglutination in blood smears and by excluding secondary
      causes of IMHA. Dogs were treated with human immune globulin (1 g/kg [0.45 g/lb]
      of body weight, i.v.) during a 6- to 12-hour period. Prednisone treatment was
      continued in all dogs, and cyclophosphamide treatment was continued in 4.
      RESULTS: Median duration of prior immunosuppressive treatment was 12.5 days.
      Short-term response could not be evaluated in 2 dogs, because they were given
      blood transfusions within 7 days after immune globulin treatment. However, there
      was a significant increase in mean Hct and hemoglobin concentration in 8 other
      dogs from day 0 to 28 after treatment. Five dogs had clinically meaningful
      responses to treatment. Three dogs were alive 12 months after treatment. There
      were not any adverse effects that could be definitively attributed to immune
      globulin treatment; however, thrombocytopenia was observed in 6 dogs after
      treatment, and evidence of thromboembolism was detected at necropsy in 5 of the 7
      dogs that died. CLINICAL IMPLICATIONS: Human immune globulin may be useful for
      short-term stabilization of some dogs with IMHA; however, it did not appear to
      improve long-term survival.

PMID- 9170089
TI  - Correlation between subjective and objective measures used to determine severity
      of postoperative pain in dogs.
AB  - OBJECTIVE: To determine the association between subjective and objective
      variables commonly used to evaluate severity of postoperative pain in dogs.
      DESIGN: Prospective double-blind study. ANIMALS: 36 dogs with unilateral rupture
      of the cranial cruciate ligament that underwent surgery to stabilize the stifle.
      PROCEDURE: Each dog was assessed to determine severity of pain before and after
      surgery, using various subjective and objective criteria. RESULTS: Subjective
      measures of pain (scores for visual analogue and numerical rating scales)
      correlated poorly or were not correlated with heart rate, respiratory rate, blood
      pressure, and results of a pain threshold test. Scores for visual analogue and
      numerical rating scales correlated with each other and with the amount of
      vocalization at most time periods. CLINICAL IMPLICATIONS: We detected a weak
      association between commonly employed subjective and objective measures of pain.
      This indicated that some of these measurement techniques do not predictably
      reflect severity of postoperative pain in dogs. Therefore, clinicians should not
      rely too heavily on these variables when assessing severity of postoperative pain
      in dogs.

PMID- 9170092
TI  - Traumatic injury of the iliopsoas muscle in three dogs.
AB  - Three dogs with injuries of the iliopsoas muscle were examined. All dogs had a
      history of trauma. On physical examination, discomfort on hyperextension of the
      hip joints was detected. Palpation and stretching of the affected muscle by
      simultaneous internal rotation and extension of the hip joint elicited signs of
      pain. Abnormalities were not detected on pelvic radiography. On the basis of
      clinical signs and lack of radiographic abnormalities, a presumptive diagnosis of
      a strain injury of the iliopsoas muscle was made. Ultrasonography confirmed the
      presumptive diagnosis and provided further information about the location and
      extent of the injury. Traumatic injury to the iliopsoas muscle should be included
      as a differential diagnosis for lameness of the pelvic limb in dogs, and
      ultrasonography can be of value in the diagnosis of muscle injuries in dogs.

PMID- 9170091
TI  - Excision of a locally invasive thymoma causing cranial vena caval syndrome in a
      dog.
AB  - A 9-year-old female Golden Retriever was examined because of inappetance, labored
      breathing, edema, and distension of the veins of the neck. Thoracic radiography
      revealed pleural effusion and a cranial mediastinal mass. Biopsy results obtained
      by use of fine-needle aspiration were consistent with thymoma. At surgery, the
      tumor was found to have invaded the cranial vena cava. Extra- and intravascular
      portions were removed without complications, and the dog's clinical signs
      resolved. To our knowledge, this is the first documented report of an invasive
      thymoma causing cranial vena caval syndrome that has been successfully treated in
      a dog. In this instance, the simplest surgical method, namely venotomy and tumor
      extraction using venous inflow occlusion, was successful, obviating the need for
      temporary or permanent vascular conduits or grafts. These findings indicate that
      there is potential for surgical correction of invasive thymoma with cranial vena
      caval syndrome in some animals, and the prognosis is not always poor.

PMID- 9170093
TI  - Ultrasonographic identification of Dirofilaria immitis in the aorta and liver of
      a dog.
AB  - A 5-year-old sexually intact male mixed-breed dog was evaluated because of
      suspected vena caval syndrome secondary to heartworm disease. On physical
      examination, the dog was thin, icteric, and weak and had tachycardia and a
      cardiac murmur. Serum biochemical and hematologic abnormalities included
      hyperbilirubinemia, high serum alkaline phosphatase and alanine transferase
      activities, hypoalbuminemia, leukocytosis, and normocytic normochromic anemia.
      Dirofilaria immitis microfilariae were seen in a blood smear. Echocardiography
      was used to confirm the diagnosis of vena caval syndrome. Multiple aberrant adult
      heartworms were evident ultrasonographically in the abdominal aorta and its
      branches and within hypoechoic nodules in the left caudal lobe of the liver. The
      dog's condition deteriorated despite supportive treatment and retrieval of 58
      adult heartworms from the right side of the heart and vena cava, and the dog was
      euthanatized. At necropsy, adult heartworms were found in the aorta and
      inflammatory hepatic nodules. To our knowledge, ultrasonographic identification
      of heartworms within the systemic arterial system and liver of a dog has not been
      described previously.

PMID- 9170094
TI  - Chinaberry poisoning in two dogs.
AB  - Two young dogs became acutely ill following ingestion of fallen fruit from a
      chinaberry tree (Melia azedarach). Clinical signs of poisoning developed within
      hours and were characteristic of gastrointestinal and CNS disturbances. Despite
      prompt and aggressive emergency treatment, neither dog survived longer than 36
      hours after the onset of clinical signs of poisoning. Necropsy of 1 dog revealed
      severe renal congestion, moderate hepatic congestion, and a moderate amount of
      serosanguineous fluid in the abdominal cavity. To the best of our knowledge,
      previous reports of chinaberry poisoning of dogs are lacking. However, chinaberry
      poisoning is well documented in human beings and other animals. Therefore, we
      strongly recommend that dogs, in addition to other animals, have restricted
      access to chinaberry trees and their fruit to prevent potential poisoning.

PMID- 9170095
TI  - Validation of a regression model for standardizing lifetime racing performances
      of thoroughbreds.
AB  - OBJECTIVE: To determine the relationship between prediction errors of a
      regression model of racing finish times and earnings or finish position; the
      relationship between standardized finish times, determined by use of this model,
      and earnings or finish position; and whether this model was valid when applied to
      data for horses that underwent surgical treatment. DESIGN: Survey. SAMPLE
      POPULATION: Records of 6,700 healthy Thoroughbreds racing in Louisiana and of 31
      Thoroughbreds with idiopathic left laryngeal hemiplegia that underwent surgical
      treatment. PROCEDURE: Predicted and standardized finish times were calculated by
      use of the regression model for healthy horses, and the relationships between
      prediction error (actual--predicted finish time) and standardized finish times,
      and earnings and finish position, were examined. Then, the regression model was
      applied to data for horses with hemiplegia to determine whether the model was
      valid when used to calculate predicted and standardized finish times for lifetime
      performance data. RESULTS: Prediction error and standardized finish times were
      negatively correlated with earnings and positively correlated with finish
      position and, thus, appeared to be reliable measures of racing performance. The
      regression model was found to be valid when applied to lifetime performance
      records of horses with laryngeal hemiplegia. CLINICAL IMPLICATIONS: Prediction
      error and standardized finish times are measures of racing performance that can
      be used to compare performances among Thoroughbred racehorses across a variety of
      circumstances that would otherwise confound comparison.

PMID- 9170096
TI  - Laparoscopic diagnosis of ischemic necrosis of the descending colon after rectal
      prolapse and rupture of the mesocolon in two postpartum mares.
AB  - Two mares were referred for evaluation after dystocia and rectal prolapse.
      Diagnostic laparoscopy, performed while the horses were standing, was used to
      evaluate the condition of the distal portion of the colon, rectum, uterus, and
      mesocolon. In both horses, laparoscopic observation revealed tears in the
      mesocolon of the descending colon. Exploration from the left or right flank was
      adequate. Because of the poor prognosis associated with the findings, euthanasia
      was elected at completion of laparoscopy. Tears in the mesocolon are not easily
      detected by use of traditional tests. Laparoscopy proved to be a more thorough
      means of evaluating the caudal portion of the abdomen including the digestive and
      urogenital tracts in these horses. As a less invasive diagnostic tool,
      laparoscopy can be performed earlier in the course of disease than alternative
      approaches for direct viewing. Furthermore, laparoscopy can be used to access the
      viability of tissues as well as the location and severity of lesions for
      prognostic purposes. The distal portion of the descending colon can also be
      evaluated to determine whether celiotomy with anastomosis or colostomy may be the
      surgical procedure of choice.

PMID- 9170097
TI  - Evaluation of cartilage lesions on the medial femoral condyle as a cause of
      lameness in horses: 11 cases (1988-1994).
AB  - OBJECTIVE: To evaluate clinical findings and response to treatment in horses in
      which cartilage lesions on the medial femoral condyle were a cause of lameness.
      DESIGN: Retrospective case series. SAMPLE POPULATION: Medical records of 11
      horses that had cartilage lesions on the medial femoral condyle detected during
      arthroscopy of the stifle. PROCEDURE: Signalment, history, lameness examination,
      response to intra-articular anesthesia, radiographs of the stifle, observations
      during diagnostic arthroscopy, and treatment were extracted from the medical
      record of each horse. Follow-up examinations and outcome were available for all
      horses. RESULTS: All horses in the study had lameness, but their gait improved
      after intra-articular injection of anesthetic. Abnormalities were not observed on
      radiography of the stifle. Diagnostic arthroscopy was performed on 12 affected
      joints in 11 horses. Cartilage was dimpled, wrinkled, and infolded, and a blunt
      arthroscopic probe could be inserted into the subchondral bone. In addition to
      focal lesions, 4 horses had generalized damage to cartilage on the medial femoral
      condyle. Focal cartilage lesions on the femoral condyle were debrided. In 2
      horses, debridement was not performed because of extensive generalized damage to
      the cartilage. Six of 7 horses with focal cartilage lesions treated by
      debridement recovered completely and resumed previous activities. CLINICAL
      IMPLICATIONS: Cartilage lesions on the medial femoral condyle can cause lameness
      in performance horses. Diagnostic arthroscopy is necessary to make an accurate
      diagnosis. Debridement of focal cartilage lesions may allow some horses to
      successfully resume performance activities.

PMID- 9170098
TI  - Neuronal and glial localization of NMDA receptors in the cerebral cortex.
AB  - The crucial role of glutamate receptors of the N-methyl-D-aspartate (NMDA) type
      in many fundamental cortical functions has been firmly established, as has its
      involvement in several neuropsychiatric diseases, but until recently, very little
      was known of the anatomical localization of NMDA receptors in the cerebral cortex
      of mammals. The recent application of molecular biological techniques to the
      study of NMDA receptors has allowed the production of specific tools, the use of
      which has much increased our understanding of the localization of NMDA receptors
      in the cerebral cortex. In particular, immunocytochemical studies on the
      distribution of cortical NMDA receptors have: 1. Demonstrated the preferential
      localization of NMDA receptors in dendritic spines, in line with previous work;
      2. Disclosed a thus far unknown fraction of presynaptic NMDA receptors on both
      excitatory and inhibitory axon terminals: and 3. Shown that cortical astrocytes
      express NMDA receptors. These studies indicate that the effects of cortical NMDA
      receptor activation are not caused exclusively by the opening of NMDA channels on
      neuronal postsynaptic membranes, as previously assumed, and that the activation
      of presynaptic and glial NMDA receptors can contribute significantly to these
      effects.

PMID- 9170099
TI  - The effects of interferon-gamma on the central nervous system.
AB  - Interferon-gamma (IFN-gamma) is a pleotropic cytokine released by T-lymphocytes
      and natural killer cells. Normally, these cells do not traverse the blood-brain
      barrier at appreciable levels and, as such, IFN-gamma is generally undetectable
      within the central nervous system (CNS). Nevertheless, in response to CNS
      infections, as well as during certain disorders in which the CNS is affected, T
      cell traffic across the blood-brain barrier increases considerably, thereby
      exposing neuronal and glial cells to the potent effects of IFN-gamma. A larger
      portion of this article is devoted to the substantial circumstantial and
      experimental evidence that suggests that IFN-gamma plays an important role in the
      pathogenesis of the demyelinating disorder multiple sclerosis (MS) and its animal
      model experimental allergic encephalomyelitis (EAE). Moreover, the biochemical
      and physiological effects of IFN-gamma are discussed in the context of the
      potential consequences of such activities on the developing and mature nervous
      systems.

PMID- 9170103
TI  - P21(Cip1/WAF1) expression in the mouse testis before and after X irradiation.
AB  - During spermatogenesis, the radiosensitivity of testicular cells changes
      considerably. To investigate the molecular mechanisms underlying these
      radiosensitivity differences, p21(Cip1/WAF1) expression was studied before and
      after irradiation in the adult mouse testis. P21(Cip1/WAF1) is a cyclin-dependent
      kinase inhibitor (CDI) and has a role in the G1/S checkpoint and differentiation.
      P21(Cip1/WAF1) expression was observed in the normal testis, using Western
      blotting analysis. After a dose of 4 Gy, but not after 0.3 Gy, an increase in
      p21(Cip1/WAF1) expression could be determined in whole testis lysates. To
      investigate which germ cells are involved in p21(Cip1/WAF1) protein expression,
      immunohistochemical analysis was performed on irradiated testis. In the normal
      testis a weak staining for p21(Cip1/WAF1) was found in pachytene spermatocytes in
      epithelial stage V up to step 5 spermatids. A dose of 4 Gy of X-irradiation
      resulted in a transient increase of p21(Cip1/WAF1) staining in these cells with a
      maximum at 6 h post irradiation, despite the fact that the irradiation did not
      induce an increase in the number of apoptotic spermatocytes. When a dose of 0.3
      Gy was given, no increase in p21(Cip1/WAF1) staining was observed. Using the
      TUNEL technique, a 10-fold increase in apoptotic spermatogonia was found after a
      dose of 4 Gy. However, no staining for p21(Cip1/WAF1) was observed in
      spermatogonia, suggesting that these cells do not undergo a p21(Cip1/WAF1)
      induced G1 arrest prior to DNA repair or apoptosis. These data imply that
      p21(Cip1/WAF1) is a factor which could be important during the meiotic prophase
      in spermatocytes and repair mechanisms in these cells, but not in spermatogonial
      cell cycle delay or apoptosis induction.

PMID- 9170104
TI  - Analysis of glutaminase activity and RNA expression in preimplantation mouse
      embryos.
AB  - Glutamine is utilized as an energy substrate in preimplantation mouse embryos.
      Glutaminase is the enzyme responsible for the conversion of glutamine to glutamic
      acid, which then enters the trichloro acetic acid (TCA) cycle as alpha
      ketoglutarate. Glutaminase enzyme activity was assessed in preimplantation
      embryos that developed in vivo, and glutaminase RNA expression was examined in
      embryos that developed in vivo or were cultured in CZB medium to various
      preimplantation stages between 1-cell and blastocyst. Glutaminase activity in 1-8
      cell-stage mouse embryos that developed in vivo ranged from 0.009-0.01 U/mg
      protein (2.39-2.95 x 10(-7) U per embryo) and increased 3-4 fold to 0.034 U/mg
      protein (8.13 x 10(-7) U per embryo) at the blastocyst stage. Relative stage
      specific expression of glutaminase RNA was assessed by reverse transcription
      polymerase chain reaction (RT-PCR) in embryos that developed both in vivo and in
      CZB culture. In vivo, glutaminase RNA was expressed at the 1-cell stage, declined
      to 23% of 1-cell levels at the early 2-cell stage, and reaccumulated from late 2
      cell through blastocyst stage, where it reached a high of 204% of 1-cell levels.
      CZB-cultured embryos exhibited a similar pattern of developmental RNA expression,
      declining to 30% of 1-cell levels at the early 2-cell stage, and increasing RNA
      expression at the blastocyst stage to 191% of the 1-cell level.

PMID- 9170102
TI  - Developmental expression and regulation of the gap junction protein and
      transcript in rat ovaries.
AB  - The extensively developed network of cell-to-cell communication, generated by gap
      junctions, mediates transmission of small molecules between the cells of the
      ovarian follicle. Our study aimed at the analysis of the ontogeny and regulation
      of connexin43 (Cx43) the ovarian gap junction protein and its gene expression
      throughout folliculogenesis. Developmental analysis was performed using ovaries
      of immature rats at different ages and selected ovarian follicles of sexually
      mature female rats at different phases of their estrous cycle. In order to
      establish the effect of hormones involved in regulation of folliculogenesis on
      Cx43 modulation, the experimental animal model of sexually immature female rats
      administered with exogenous gonadotropins was employed. Developmental and
      hormonal modulations of Cx43 protein and its mRNA expression were studied by
      Western and Northern blot analysis, respectively. We found that Cx43 was
      undetectable in ovaries of rats on the first postnatal day, with a low level of
      this protein observed in 11-day-old rats ovaries. Some increase in the amount of
      Cx43 was observed at the age of 25 days with a dramatic elevation accompanied by
      phosphorylation of this protein that was specific to large antral follicles of
      sexually mature proestrous rats. Elimination of the protein was observed at
      estrus and could be prevented by cancellation of the preovulatory surge of
      luteinizing hormone (LH). This pattern of Cx43 modifications was mimicked by
      exogenous administration of hormones as follows: Pregnant mare's serum
      gonadotropin (PMSG) increased the Cx43 protein expression with a concurrent
      induction of its phosphorylation while a further human chorionic gonadotropin
      (hCG) injection resulted in a decrease of the signal. Analysis of the Cx43 mRNA
      showed a direct correlation between the Cx43 protein level and its gene
      expression. We conclude that: 1) At early folliculogenesis the ovarian gap
      junction protein Cx43 and its gene are developmentally regulated; and 2) After
      antrum formation, transcription, translation, and posttranslational modifications
      of Cx43 are regulated by gonadotropins.

PMID- 9170105
TI  - Nuclear transfer in sheep embryos: the effect of cell-cycle coordination between
      nucleus and cytoplasm and the use of in vitro matured oocytes.
AB  - The developmental ability of nuclear transplant sheep embryos derived from in
      vitro matured oocytes was studied by controlling cell-cycle coordination of donor
      embryonic nuclei and recipient cytoplasts. Oocytes were recovered from nonatretic
      antral follicles of adult sheep ovaries and cocultured with follicle shells in
      M199-based medium supplemented with gonadotrophins in a nonstatic system.
      Effective activation if IVM oocytes was obtained by applying two pulses of 1.0
      kv/cm 22 min apart in inositol-based electroporation medium to oocytes matured in
      vitro for 27 hr. Synthesis of DNA (S-phase) was assessed by BrdU incorporation
      and was found to initiate around 5 hpa (hours postactivation) and to persist
      until 18 hpa. Mitotic blastomeres were induced by treating embryos with 6.6
      microM nocodazole for 14-17 hr. Three types of transfers were compared directly:
      "S-->S," early embryonic nuclei (mostly in S-phase) were transferred to
      presumptive S-phase cytoplasts; "M-->MII," nocodazole-treated embryonic nuclei
      (most in M-phase) were transferred to MII-phase cytoplasts; and control (S-
      >MII), conventional nuclear transfer of fusion and activation simultaneously. The
      results showed that fusion and recovery rates did not differ among the three
      groups. However, after 6 days of in vivo culture, the morula and blastocyst
      formation rate was significantly higher for the M-->MII combination than for the
      control (28.3% vs. 8.1%, P < 0.05), while no significant differences in
      developmental rate were observed between S-->S and M-->MII, and between S-->S and
      control, though developmental rate was also increased for S-->S compared to
      control (20.9% vs. 8.1%, P > 0.05). Transfer of blastocysts derived from M-->MII
      or S-->S nuclear cytoplasmic reconstitution to synchronized recipient ewes
      resulted in the birth of lambs. These data suggest that in vitro matured oocytes
      can support full-term development of nuclear transplant sheep embryos when the
      cell cycle of nucleus and cytoplasm is coordinated, and that M-->MII nuclear
      transfer might be an efficient and simple way to improve the developmental
      competence of the reconstituted embryos.

PMID- 9170106
TI  - Requirement for protein synthesis during embryonic genome activation in mice.
AB  - Embryonic genome activation (EGA) occurs by the 2-cell stage in mouse embryos. To
      understand the molecular basis of EGA, it is important to determine whether EGA
      can be supported by maternally inherited factors or if it requires the synthesis
      of additional transcription factors. We used a quantitative reverse transcription
      polymerase chain reaction (RT-PCR) method to test whether protein synthesis is
      required for the transcriptional activation of six housekeeping genes (U2afbp-rs,
      Hprt, Pdha1, Prps1, Odc, and Cox7c). Cycloheximide treatment reduced the
      expression of these mRNAs in 2-cell embryos to the same degree as alpha-amanitin
      treatment. Cycloheximide treatment did not reduce the expression of maternally
      inherited mRNAs, indicating that its effect is specific for transcription
      dependent gene expression. These results contrast with earlier results reported
      for the Hsp70 gene. This difference may reflect differences in promoter
      requirements. We conclude that protein synthesis is required for the activation
      of most, if not all, housekeeping genes in the mouse embryo, and that the time of
      EGA may be controlled, in part, by the regulated recruitment of maternal mRNAs
      encoding key transcription factors.

PMID- 9170107
TI  - Expression and function of amphiregulin during murine preimplantation
      development.
AB  - Amphiregulin (Ar) is an EGF receptor ligand that functions to modulate the growth
      of both normal and malignant epithelial cells. We asked whether mouse
      preimplantation embryos express Ar, and if so, what the function of Ar is during
      preimplantation development. We used RT-PCR to show expression of Ar mRNA in
      mouse blastocysts, and using a polyclonal anti-Ar antibody and indirect
      immunofluorescence, we detected the presence of Ar protein in morula- and
      blastocyst-stage embryos. Ar protein was present in both the cytoplasm and
      nucleus in both morulae- and blastocyst-stage embryos, which is similar to Ar
      distribution in other cell types. Embryos cultured in Ar developed into
      blastocysts more quickly and also exhibited increased cell numbers compared to
      control embryos. In addition, 4-cell stage embryos cultured in an antisense Ar
      phosphorothioate-modified oligodeoxynucleotide (S-oligo) for 48 hr exhibited
      slower rates of blastocyst formation and reduced embryo cell numbers compared to
      embryos exposed to a random control S-oligo. TGF-alpha significantly improved
      blastocyst formation, but not cell numbers, for embryos cultured in the antisense
      Ar S-oligo. From these observations, we propose that Ar may function as an
      autocrine growth factor for mouse preimplantation embryos by promoting blastocyst
      formation and embryo cell number. We also propose that blastocyst formation is
      stimulated by Ar and TGF-alpha, while Ar appears to exert a greater stimulatory
      effect on cell proliferation than does TGF-alpha in these embryos.

PMID- 9170108
TI  - Establishment and characterization of a conditionally immortalized smooth
      muscle/myometrial-like cell line.
AB  - A novel smooth muscle/myometrial-like cell line, SMU1-10, has been generated from
      the uterus of a H-2Kb-tsA58 transgenic mouse carrying a thermolabile SV40 large T
      antigen gene. These cells grow continuously when maintained at the permissive
      temperature (33 degrees C) for the SV40 large T-antigen but stop dividing when
      placed at the non-permissive temperature (39 degrees C) and ultimately die within
      3 weeks. All of the SMU1-10 cells produce smooth muscle alpha-actin (SMAA) at
      both 33 degrees C and 39 degrees C. A subset of the cells also contain smooth
      muscle gamma-actin (SMGA), a hallmark of smooth muscle differentiation, and the
      fraction of cells staining for this actin increases from about 1% when maintained
      for three days at 33 degrees C to as much as 30% at 39 degrees C over the same
      length of time. However, the appearance of SMGA in SMU1-10 cells appears to be
      regulated mainly at a post-transcriptional level since in situ hybridization
      indicates that all cells contain SMGA mRNA at both 33 degrees C and 39 degrees C.
      SMU1-10 cultures also contain smooth muscle myosin heavy chain (SM-MHC) and SM22
      alpha, both of which are only found in smooth muscle of the adult mouse. Three
      additional smooth muscle (myometrium)-related markers, connexin 43, the
      thromboxane A2 receptor, and the progesterone receptor also are present in these
      cells. At the nonpermissive temperature for SV40 large T-antigen, the both level
      of SMGA mRNA and the number of cells staining for this actin are significantly
      increased in the presence of progesterone, a process that is similar to the
      upregulation of SMGA in the myometrium late in pregnancy. Overall, SMU1-10 cells
      provides a potentially useful in vitro model system to study smooth
      muscle/myometrial differentiation.

PMID- 9170100
TI  - Activity-dependent changes in voltage-dependent calcium currents and transmitter
      release.
AB  - Voltage-dependent Ca2+ channels are important in the regulation of neuronal
      structure and function, and as a result, they have received considerable
      attention. Recent studies have begun to characterize the diversity of their
      properties and the relationship of this diversity to their various cellular
      functions. In particular, Ca2+ channels play a prominent role in depolarization
      secretion coupling, where the release of neurotransmitter is very sensitive to
      changes in voltage-dependent Ca2+ currents. An important feature of Ca2+ channels
      is their regulation by electrical activity. Depolarization can selectively
      modulate the properties of Ca2+ channel types, thus shaping the response of the
      neuron to future electrical activity. In this article, we examine the diversity
      of Ca2+ channels found in vertebrate and invertebrate neurons, and their short-
      and long-term regulation by membrane potential and Ca2+ influx. Additionally, we
      consider the extent to which this activity-dependent regulation of Ca2+ currents
      contributes to the development and plasticity of transmitter releasing
      properties. In the studies of long-term regulation, we focus on crustacean
      motoneurons where activity levels, Ca2+ channel properties, and transmitter
      releasing properties can be followed in identified neurons.

PMID- 9170109
TI  - Effects of castration on thiol status in rat spermatozoa and epididymal fluid.
AB  - Mammalian spermatozoa gain their fertilizing ability as they mature in the
      epididymis, a process which is accompanied by oxidation of sperm protein thiols.
      Since sperm maturation is dependent upon normal androgenic support to the
      epididymis, the present work was designed to study the effects of castration on
      thiol status. Spermatozoa and epididymal fluid were isolated from the
      epididymides of male rats 5 days after castration or after 11 daily injections of
      the antiandrogen, cyproterone acetate. Spermatozoa and epididymal fluid were
      labeled with the fluorescent thiol labeling agent monobromobimane. Intact
      spermatozoa were evaluated by fluorescence microscopy, protein thiols were
      analyzed by electrophoresis, and fertilizing ability was examined after
      insemination of sperm suspension into the uterine horns of immature superovulated
      female rats. We found that both treatments resulted in an increase in cauda sperm
      thiols as shown by increased fluorescence in the intact spermatozoa. Protamines
      and nonbasic proteins were found to have increased levels of reactive thiols. The
      protein profiles of epididymal fluid from castrated rats were different from
      those of the controls, and the fluorescence patterns corresponded to the protein
      profiles. Our results indicate that testosterone withdrawal leads to inhibition
      of sperm thiol oxidation.

PMID- 9170110
TI  - Role of amphibian egg transglutaminase in the development of secondary cytostatic
      factor in vitro.
AB  - Fresh cytosols extracted from unfertilized amphibian eggs contain a cytostatic
      factor (CSF) which arrests the cell cycle at metaphase when microinjected into
      cleaving blastomeres. This CSF is sensitive to Ca2+, and is designated primary
      CSF (1 degree CSF). During storage of Ca(2+)-containing cytosols at 2 degrees C,
      stable CSF activity appears, designated secondary CSF (2 degrees CSF). In Rana
      pipiens egg cytosols, the development of 2 degrees CSF coincides with the
      formation of a protein complex with a molecular weight above 2,000 kDa, and this
      large molecule exhibits a high 2 degrees CSF activity when purified (Shibuya and
      Masui, 1989: Development 106:799-808). The present study shows that both the
      formation of 2 degrees CSF protein complex and the development of its activity
      are inhibited by ethylamine and glycine-ethyl-ester (GEE), both known as potent
      transglutaminase (TGase) inhibitors. An affinity-purified polyclonal antibody
      raised against mammalian transglutaminase reacts with an approximately 68-kDa
      protein in fresh egg cytosols, as well as with the 2 degrees CSF protein complex.
      In cytosols deprived of transglutaminase by immunoprecipitation, neither the
      development of 2 degrees CSF activity nor the formation of its protein complex
      can occur. These results indicate that transglutaminase of Rana pipiens eggs is
      responsible or the formation of 2 degrees CSF, and that transglutaminase itself
      is incorporated into 2 degrees CSF molecules.

PMID- 9170111
TI  - In vitro analysis of oocyte cumulus complex pickup rate in the hamster
      Mesocricetus auratus.
AB  - In mammals, the oocyte and its surrounding cumulus cells constitute on oocyte
      cumulus complex (OCC). During ovulation, OCCs are extruded into the peritoneal or
      bursal cavity, depending on the species, and are then rapidly picked up by the
      fimbria on the outer surface of the oviductal infundibulum and transported to the
      ampulla, where fertilization occurs. We developed a method to measure OCC pickup
      rates quantitatively in vitro, and we used this method to evaluate the effects of
      viscosity and temperature on pickup rates. Hamster infundibula are placed in a
      holding pipette in a chamber modified to study OCC pickup. Ciliary beat
      frequencies (CBF) can be measured in the same preparation. Pickup rates vary
      depending on the pathway on which the OCC travels over the surface of the
      infundibulum; however, rates for a given pathway are very consistent. The average
      pickup rate at room temperature calculated from three different
      pathways/infundibulum was 55.2 +/- 10.6 microns/sec. Both rates between
      infundibula from the same female and rates among infundibula from different
      females were in most cases similar. Preparations preincubated in vitro for 2.75
      hr produced rates similar to nonpreincubated samples, while longer preincubation
      resulted in decreased rates. Inclusion of Ficoll in culture medium to increase
      viscosity caused a concentration-dependent decrease in both OCC pickup rate and
      in CBF. However, a significant decrease in OCC pickup rate was only observed at
      viscosities higher than those found in bursal fluid. When trials were run at
      physiological temperature (36.4 degrees C) rather ambient temperature, rates
      increased to 136.7 +/- 29.9 (SD) microns/sec. Linear regression analysis
      demonstrated a strong positive correlation (r = 0.94) between OCC pickup rate and
      temperature. The OCC pickup rate assay can be used experimentally, and should be
      valuable in evaluating factors that affect rate and in studies dealing with the
      mechanism of OCC pickup.

PMID- 9170112
TI  - Sperm-egg interaction in the painted frog (Discoglossus pictus): an
      ultrastructural study.
AB  - The ultrastructure of sperm changes and penetration in the egg was studied in the
      anuran Discoglossus pictus, whose sperm have an acrosome cap with a typical tip,
      the apical rod. The first stage of the sperm apical rod and acrosome reaction
      (AR) consists in vesiculation between the plasma membrane and the outer acrosome
      membrane. The two components of the acrosome cap are released in sequence. The
      innermost component (component B) is dispersed first. The next acrosome change is
      the dispersal of the outermost acrosome content (component A). At 30 sec
      postinsemination, when the loss of component B is first observed, holes are seen
      in the innermost jelly coat (J1), surrounding the penetrating sperm. Therefore,
      this acrosome constituent might be related to penetration through the innermost
      egg investments. At 1 min postinsemination, during sperm penetration into the
      egg, a halo of finely granular material is observed around the inner acrosome
      membrane of the spermatozoon, suggesting a role for component A at this stage of
      penetration. Gamete-binding and fusion take place between D1 (the egg-specific
      site for sperm interaction) and the perpendicularly oriented sperm. Spermatozoa
      visualized at their initial interaction (15 sec postinsemination) with the
      oolemma are undergoing vesiculation. The first interaction is likely to occur
      between the D1 glycocalyx and the plasma membrane of the hybrid vesicles
      surrounding the apical rod. As fusion is observed between the internal acrosome
      membrane and the oolemma, it can be postulated that gametic interaction might be
      followed by fusion of the latter with the apical rod internal membrane that
      extends posteriorly into the inner acrosome membrane. Insemination of the
      outermost jelly layer (J3) dissected out of the egg, and observations of the
      ultrastructural changes of spermatozoa in this coat, indicate that J3 rather than
      the vitelline coat (VC) induces the AR. Interestingly, at the late
      postinsemination stage, VC fibrils are seen crosslinking the inner acrosome
      membrane. The role of this binding is here discussed.

PMID- 9170113
TI  - Cortical granule exocytosis in hamster eggs requires microfilaments.
AB  - Earlier work has demonstrated that hamster eggs that do not release a second
      polar body after fertilization in vitro lack a block to polyspermy (Stewart
      Savage and Bavister, 1987: Gamete Res 18:333-338). Since polar body release
      requires microfilaments, the involvement of microfilaments in cortical granule
      exocytosis was examined. When hamster eggs were treated with cytochalsin B (CB)
      for 1 hr and then coincubated with sperm for 90 min, there was a dose-dependent
      increase in both the percentage of eggs with more than one sperm penetrating the
      zona pellucida and the mean number of sperm that penetrated the zona, with a
      maximum effect at 20 micrograms CB/ml (100% polypenetration, 3.0 +/- 0.3
      sperm/egg). Cytochalasin-treated eggs retained 85% of their cortical granules 55
      min after insemination, as compared to unfertilized eggs. Longer time periods did
      not result in any further reduction. As seen with the scanning confocal
      microscope, an extensive microfilament network was present in the cortex of
      untreated eggs, with the cortical granules located within the cortical network.
      The cortical microfilament network was highly reduced in CB-treated eggs. When
      viewed with the electron microscope, the same number of cortical granules were
      located next to the plasma membrane in both cytochalasin-treated and untreated,
      unfertilized eggs. These data indicate that intact microfilaments are required
      for normal cortical granule exocytosis in the hamster egg, but the role of the
      microfilaments in exocytosis is unresolved.

PMID- 9170114
TI  - A maturation-related differential phosphorylation of the plasma membrane proteins
      of the epididymal spermatozoa of the hamster by endogenous protein kinases.
AB  - When the plasma membranes of caput and cauda epididymal spermatozoa of hamster
      were evaluated for their ability to undergo phosphorylation, a differential
      phosphorylation of the membrane proteins was observed. In the plasma membranes of
      the caput epididymal spermatozoa (immature), twelve proteins were phosphorylated
      (100, 76, 67, 65, 55, 52, 47, 42, 38, 32, 30, and 20 kD), whereas in the plasma
      membranes of cauda epididymal spermatozoa (mature), a differential
      phosphorylation pattern was observed with respect to the 94, 67, 52, and 47 kD
      proteins. The 94 kD protein was found to be phosphorylated and the 67 kD protein
      was found to be not phosphorylated in cauda spermatozoal plasma membrane (Cd SPM)
      in contrast to this protein in caput spermatozoal plasma membrane (Cpt SPM). The
      52 and 47 kD proteins were also more intensely phosphorylated in Cd SPM than Cpt
      SPM. The 100 kilodalton protein, although present in both Cpt and Cd sperm plasma
      membranes, was found to be phosphorylated at the tyrosine residues only in the Cd
      SPM, as indicated by the Western blot using antiphosphotyrosine antibody.
      Further, a differential phosphorylation of the substrate proteins present in the
      Cpt and Cd SPM was seen when Mg2+ in the assay buffer was replaced by other
      divalent cations. For instance, Zn2+ stimulated the phosphorylation of an 85 kD
      protein in cauda SPM and not in the caput SPM and Ca2+ stimulated the
      phosphorylation of a 76 kD protein only in the cauda SPM. The phosphoproteins in
      both the plasma membranes were found to be phosphorylated predominantly at the
      tyrosine residue. The differential phosphorylation at a 100 kD protein at
      tyrosine in the Cd SPM (Western blot), which is absent in the immature Cpt SPM,
      also indicated that certain proteins in the hamster spermatozoa are
      phosphorylated in a maturation-specific manner.

PMID- 9170115
TI  - Sleep anomalies in the chronic fatigue syndrome. A comorbidity study.
AB  - Polysomnographic findings were compared between a group of patients with the
      chronic fatigue syndrome (CFS; n = 49) and a matched healthy control (HC) group
      (n = 20). Sleep initiation and sleep maintenance disturbances were observed in
      the CFS group. The percentage of stage 4 was significantly lower in the CFS
      group. A discriminant analysis allowed a high level of correct classification of
      CFS subjects and HC. Sleep-onset latency and the number of stage shifts/hour
      contributed significantly to the discriminant function. The presence of these
      anomalies as well as the decrease in stage 4 sleep were not limited to the
      patients also diagnosed with fibromyalgia or with a psychiatric disorder. No
      association was found between sleep disorders and the degree of functional status
      impairment. The mean REM latency and the percentage of subjects with a shortened
      REM latency were similar in CFS and HC.

PMID- 9170116
TI  - Changes in acute-phase proteins during lithium potentiation of antidepressants in
      refractory depression.
AB  - This study was performed on 32 patients with refractory depression in whom
      lithium was added to antidepressant treatment in order to potentiate the
      therapeutic effect, and in 20 healthy controls. Plasma concentration of three
      acute-phase proteins (APPs): C-reactive protein, alpha-1-acid glycoprotein (AGP)
      and alpha-1-antichymotrypsin (ACT) as well as microheterogeneity of AGP and ACT
      were measured, before and after 4 weeks of lithium addition to antidepressants.
      Before Li addition, all patients studied had elevated values of APPs, which
      suggested the existence of immunological activation. A significant decrease in
      plasma levels of all APPs and the decrease of glycosylation values of AGP and ACT
      was observed after Li potentiation. A favorable clinical effect of lithium
      potentiation after 4 weeks was found in 24 patients (75%). Nonresponders to Li
      potentiation differed from responsers by their immunological indices prior to Li
      addition. They had higher values of reactivity coefficients, which means more
      inflammatory patterns.

PMID- 9170117
TI  - Plasma levels of cyclic GMP, immune parameters and depressive status during
      interferon therapy. A prospective study in Japan.
AB  - In this report, we investigated the relationship between depressive symptoms and
      plasma interferon (IFN)-alpha-like immunoreactivity, cyclic GMP (cGMP) and
      soluble interleukin-2 receptor (sIL-2R) levels during IFN therapy. An altered
      mood state was observed in 5 of 26 patients. IFN-alpha-like immunoreactivity in
      the depressed group tended to be elevated. cGMP levels of depressed patients were
      significantly greater than those of control subjects before and 6 weeks after IFN
      therapy. However, sIL-2R levels were not different between the two groups. These
      results suggest that a number of patients suffered from depression during IFN
      therapy and that patients had greater concentrations of cGMP levels.

PMID- 9170118
TI  - Pathophysiology and psychopharmacology of dementia--a new study design. 2.
      Cyclandelate treatment--a placebo-controlled double-blind clinical trial.
AB  - The aim of this randomized, double-blind, placebo-controlled 16-week study was to
      investigate the clinical efficacy of cyclandelate (Natil, 1,600 mg/day) in 139
      adult outpatients with cognitive impairment (70 allocated to cyclandelate; 69 to
      placebo). Quantitative-topological EEG, event-related potentials (P300) and
      psychophysiological interview-based rating scales were used. The efficacy of
      cyclandelate was demonstrated in the confirmatory statistical sense using a
      global Hailperin-Ruger test on 10 predefined primary variables at global
      significance level of 0.05 relating to psychopathology, psychometry,
      neuropsychophysiology and behavior. At psychopathological and behavioral level
      the reduction of the total scores of the rating scales (Alzheimer Disease
      Assessment Scale, Sandoz Clinical Assessment Geriatric Scale, and Nurnberger
      Selbsteinschatzungs-Liste) following a 16-week therapy revealed also an
      individual significant cyclandelate-placebo distinction in the confirmatory
      statistical sense. A difference between verum and placebo was also observed by
      the increase of the number of correct answers during performance of the number
      symbol test (psychometrical level). The objective electrophysiological data
      (neuropsychophysiological level) support these findings. Of particular interest
      is that following cyclandelate treatment the absolute theta power remained almost
      unchanged and an increase of P300 amplitude was observed. At the same time
      placebo led to a distinct theta power increase and a decrease of P300 amplitude,
      which was interpreted as the reflection of an impairment of the initial clinical
      state. Summarizing, cyclandelate proved to be efficacious compared to placebo in
      patients with mild to moderate cognitive impairment.

PMID- 9170119
TI  - Glucocorticoids and anabolic/androgenic steroids inhibit the synthesis of
      GABAergic steroids in rat cortex.
AB  - Cerebral side effects of therapy with glucocorticoids include mental alterations
      and behavioral disturbances such as nervousness, insomnia, changes in mood or
      psychological state and psychopathies of manic-depressive or schizophrenic type.
      We have investigated the effects of glucocorticoids, anabolic/androgenic steroids
      and the 5-alpha-reductase inhibitor N,N-bis (1-methyl)-3-oxo-4-aza-5-alpha
      androstane-17-beta-carboxamide (1-MAC) on the synthesis of the GABAergic steroids
      5-alpha-pregnane-3.20-dione (5-alpha-dihydroprogesterone) and 5-alpha-pregnane-3
      alpha-ol-20-one (5-alpha-tetrahydroprogesterone) in rat cortex in vitro. We found
      potent inhibition of progesterone-3-alpha-hydroxysteroid dehydrogenase (3-alpha
      HSDH) by prednisone, prednisolone, dexamethasone and fluocortolone. Inhibition of
      progesterone 5-alpha-reductase by glucocorticoids was not found. In addition,
      inhibition of 3-alpha-HSDH and 5-alpha-reductase by androgenic/anabolic steroids
      and inhibition of 5-alpha-reductase by 1-MAC could be demonstrated. The
      inhibition of progesterone metabolism in the cerebral cortex by exogenous
      steroids might lead to altered neuronal activity. We conclude that this mechanism
      could induce the cerebral side effects, such as mental modifications and
      behavioral disturbances, of the drugs investigated.

PMID- 9170120
TI  - Assessment of cognitive performance after progesterone administration in healthy
      male volunteers.
AB  - Administration of progesterone produces sleep EEG patterns that resemble those of
      agonistic modulators at the GABAA receptor. Previous studies evaluating the
      effects of an oral progesterone administration on attention performance in
      females pointed to putative sedative effects of progesterone at high dosages.
      However, no data are available whether progesterone dosages that influence sleep
      produce sedative hangover effects on the following morning. Therefore, we
      assessed the effects of a single oral dose of 300 mg micronized progesterone
      administered in the evening on cognitive performance parameters in male healthy
      volunteers on the following morning using a placebo-controlled double-blind
      crossover design. There was a great variability in bioavailability following
      progesterone intake. The administration of progesterone produced no consistent
      effects on attention performance. Thus, dosages of progesterone that are
      sufficient to modulate sleep are not likely to exert sedative hangover effects.

PMID- 9170122
TI  - Right ventricular outflow tract pacing.

PMID- 9170121
TI  - Relationship between the effects of a hypnotic drug, zopiclone, on
      polysomnography and on daytime EEGs.
AB  - The correlation between the effects of zopiclone (ZPC), a nonbenzodiazepine
      hypnotic drug, on sleep polysomnograms and on daytime EEGs was examined in 12
      healthy adult male volunteers. Sleep polysomnograms were recorded after a single
      oral administration of ZPC 10 mg or placebo according to the double-blind
      crossover method. Daytime EEGs were recorded after the administration of ZPC, 7.5
      mg, or placebo in the same manner, and recorded for 3 min with closed eyes at
      rest. Then, square roots of the absolute power (amplitude) of the delta-, theta-,
      alpha-, and beta-activities were calculated from the power spectrum obtained by
      the fast Fourier transform method. As a result, ZPC decreased the percentage of
      stage 1 sleep in total sleep time, while it increased the percentage of stage 2,
      total sleep time, and time of slow wave sleep in the first and second sleep
      cycles (SWS 1 and 2). Changes in SWS 1 and 2 correlated positively with the
      amplitude changes in daytime resting delta-activity. This indicates that the
      increase of SWS due to ZPC could be related to the change of delta-activity in
      the daytime resting EEG.

PMID- 9170123
TI  - Permanent pacing in Ebstein's anomaly.
AB  - Patients with Ebstein's anomaly present unique challenges to permanent pacing due
      to anatomical variations and tricuspid valve replacement. We retrospectively
      reviewed our experience with permanent pacing in patients with Ebstein's anomaly
      between 1976 and 1993. We identified 401 patients with Ebstein's anomaly, of whom
      15 (3.7%) required permanent pacing (1 of the 15 was implanted elsewhere). Of the
      15, there were 8 females and 7 males (mean age 32 years [range 7-74]); the
      indications for pacing were AV block in 11 and sinus node dysfunction in 4. Eight
      patients were programmed with VVI and seven with DDD. All VVI patients were paced
      epicardially. Two patients with DDD pacemakers had transvenous atrial and
      ventricular leads, 4 DDD patients had transvenous atrial leads and epicardial
      ventricular leads, and 1 patient had both epicardial and transvenous systems.
      Associated surgical procedures included tricuspid valve replacement in 14 of 15,
      atrial septal defect repair in 10 of 15, atrioplasty in 7 of 15, prior tricuspid
      annuloplasty in 4 of 15, pulmonary vein dilation in 1 of 15, and conduction
      system ablation in 2 of 15. Patients had a mean follow-up of 35 months (range 1
      168 months). Complications requiring operative intervention occurred in four
      patients. One patient had displacement of a transvenous ventricular lead. A
      second patient had an epicardial lead failure. A third patient had a
      nonfunctioning atrial lead that displaced across the tricuspid valve, causing
      severe tricuspid regurgitation. The fourth patient had multiple epicardial and
      endocardial leads exit block with secondary diaphragmatic stimulation. Permanent
      pacemakers were required in 3.7% of patients with Ebstein's anomaly, with the
      indication being intrinsic conduction disease in the majority of patients. Ninety
      three percent of patients required tricuspid valve replacement, suggesting more
      severe manifestation of Ebstein's anomaly. Twenty-seven percent had complications
      requiring surgical intervention. Thus, permanent pacing in patients with
      Ebstein's anomaly can be challenging and should be approached by an experienced
      physician.

PMID- 9170101
TI  - The cellular and molecular basis of peripheral nerve regeneration.
AB  - Functional recovery from peripheral nerve injury and repair depends on a
      multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival
      after axotomy is a prerequisite for regeneration and is facilitated by an array
      of trophic factors from multiple sources, including neurotrophins, neuropoietic
      cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived
      neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting
      mode to a growth mode and express growth-associated proteins, such as GAP-43,
      tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all
      of which have the potential to promote axonal regeneration. Axonal sprouts must
      reach the distal nerve stump at a time when its growth support is optimal.
      Schwann cells in the distal stump undergo proliferation and phenotypical changes
      to prepare the local environment to be favorable for axonal regeneration. Schwann
      cells play an indispensable role in promoting regeneration by increasing their
      synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N
      cadherin, and L2/HNK-1, by elaborating basement membrane that contains many
      extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by
      producing many neurotrophic factors and their receptors. However, the growth
      support provided by the distal nerve stump and the capacity of the axotomized
      neurons to regenerate axons may not be sustained indefinitely. Axonal
      regenerations may be facilitated by new strategies that enhance the growth
      potential of neurons and optimize the growth support of the distal nerve stump in
      combination with prompt nerve repair.

PMID- 9170124
TI  - PR interval adaptation in the denervated transplanted heart.
AB  - In the present study, the dynamic PR response upon standardized treadmill
      exercise was investigated in 21 transplant recipients (recipient age 48 +/- 17
      years, donor age 31 +/- 12 years, > 1 year after transplantation). HR and PR
      interval were measured at rest and at the end of each 25-W increase in workload
      till peak exercise. In 17 cases norepinephrine (NE) was assessed at rest, and at
      the end of each workload the HR increased from 99.3 +/- 14 to 143.4 +/- 25
      beats/min at individual peak exercise, and NE increased from 1,307 +/- 1,163 to
      3,688 +/- 2,036 pg/mL, while the PR interval shortened from 149.2 +/- 13 to 119.3
      +/- 20 ms. On average, PR decreased by 3.4 ms for a 10-beat increase in HR, and
      the HR-PR interval relationship was described by a linear regression (y = 176.8
      0.3469x, P = 0.0001). One patient who was unable to increase his NE levels upon
      exercise showed virtually no decrease in the PR interval and no HR increase. Both
      recipient age and donor age were moderately and significantly related to the
      minimum PR interval achieved at peak exercise (r = 0.6, P = 0.008 and r = 0.51. P
      = 0.049, respectively). These data show the following: (1) adaptation of the PH
      interval upon exercise does occur in the denervated transplanted heart; (2) the
      HR-PR relation is similar to that reported in the innervated heart; (3) the
      overall decline in PR interval is blunted, since denervated patients start at
      shorter resting PR intervals and achieve relatively longer PR intervals at peak
      exercise when compared to their innervated counterparts; (4) these exercise
      induced changes of the PR interval may be explained by circulating NE; and (5) NE
      levels achieved at peak exercise and the sensitivity of the AV node to NE seem to
      be age related.

PMID- 9170126
TI  - Modification of atrioventricular nodal electrophysiology by selective
      radiofrequency delivery on the anterior or posterior approaches.
AB  - An analysis was made in 14 isolated and perfused rabbit hearts of the
      electrophysiological effects of selective radiofrequency (RF) delivery in the
      anterior (group I, n = 7) or posterior zone (group II, n = 7) of the Koch
      triangle, with the aim of modifying atrioventricular nodal (AVN) conduction
      without suppressing 1:1 transmission. After opening the right atrium, RF was
      delivered (0.5 W) with a 1-mm diameter unipolar electrode positioned in the
      selected zone until a prolongation of no less than 15% was obtained in the
      Wenckebach cycle length (WCL). Before and after (30 min) RF, anterograde and
      retrograde AVN refractoriness and conduction were evaluated, stimulating from the
      crista terminalis (CT), the interatrial septum (IAS), and from the RV epicardium.
      After RF, the following percentage increments were observed in group I: AH(CT) =
      36% +/- 9%, AH(IAS) = 38% +/- 11%, WCL(CT) = 28% +/- 8%, WCL(IAS) = 22% +/- 6%,
      functional refractory period (FRP) of the AVN(CT) = 13% +/- 11%, FRP-AVN(IAS) =
      13% +/- 8%, retrograde WCL = 20% +/- 19%, and retrograde FRPVA = 13% +/- 16%. The
      increments observed in group II and the significances of the differences with
      respect to group I were: AH(CT) = 11% +/- 14% (P < 0.01), AH(IAS) = 19% +/- 32%
      (NS), WCL(CT) = 42% +/- 14% (P < 0.05), WCL(IAS) = 42% +/- 16% (P < 0.01), FRP
      AVN(CT) = 28% +/- 28% (NS), FRP-AVN(LAS) = 21% +/- 19% (NS), retrograde WCL = 35%
      +/- 24% (NS), and retrograde FRP = 16% +/- 13% (NS). In both groups, the AH
      interval variations were not correlated with those of the rest of the parameters
      analyzed. Truncated nodal function curves suggestive of a dual AV nodal pathway
      were obtained in three experiments, though in only one of them was this observed
      under basal conditions. In the other two experiments, with dual AV nodal
      physiology only after RF (one from each group), AV nodal reentrant tachycardias
      were triggered with atrial extrastimulus at coupling intervals equal to or
      shorter than at those that cause a sudden lengthening of the AH interval, RF
      delivered in the anterior and posterior zones of the Koch triangle produced
      effects of different magnitude on the AH interval and Wenckebach cycle length. In
      the anterior zone the AH interval was prolonged to a greater extent, while in the
      posterior zone the effects were greater on the Wenckebach cycle length. No
      correlation existed between the variations in AH interval and Wenckebach cycle
      length, regardless of where RF was delivered. The evaluation of anterograde AV
      nodal refractoriness was similar when stimulating from the crista terminalis or
      from the interatrial septum. By delivering RF, it was possible to induce dual AV
      nodal physiology and reentrant tachycardias.

PMID- 9170125
TI  - Temperature guided radiofrequency catheter ablation of myocardium: comparison of
      catheter tip and tissue temperatures in vitro.
AB  - Temperature monitoring during RF ablation has been proposed as a means of
      controlling the creation of the lesion. However, in vivo studies have shown poor
      correlation between lesion size and catheter tip temperature. Thus, we
      hypothesized a difference between catheter tip and tissue temperatures during RF
      catheter ablation, and that this difference may depend on flow passing the
      ablation site, tip electrode length, and catheter-tissue orientation. In vitro
      studies were performed using four different ablation catheters (tip electrode
      length: 2, 4, or 6 mm) with a thermistor or a thermocouple as temperature sensor.
      Set temperature was 70 degrees C and pulse duration was 30 seconds. Pieces of
      porcine left ventricle were immersed in a bath of isotonic saline-dextrose
      solution at 37 degrees C. The ablation catheters were positioned perpendicularly,
      obliquely, or parallel to the endocardium. A temperature sensor was inserted from
      the epicardial side and positioned 1 mm beneath the catheter-tissue interface.
      Experiments were made with a flow of 200 mL/min passing the ablation site or with
      no flow. The catheter tip and tissue temperatures differed significantly (P <
      0.0001) during ablation. This difference increased with time, with flow passing
      the ablation site, with the length of the tip electrode, and when the catheter
      was positioned perpendicularly or obliquely to the endocardium as compared to the
      parallel catheter-tissue orientation (P < 0.05). In conclusion, the tissue
      temperature may far exceed the catheter tip temperature, and intramyocardial
      superheating resulting in steam formation and popping may occur despite a
      relatively low catheter tip temperature.

PMID- 9170127
TI  - Ambulatory electrocardiography for the detection of pacemaker lead failure.
AB  - The suboptimal performance of some polyurethane bipolar pacing leads has
      highlighted concern about the optimal method of monitoring pacemaker lead
      performance. Since the manifestations of premature lead failure may be initially
      intermittent, we hypothesized that ambulatory electrocardiography (AECG) would be
      a more sensitive tool for the detection of pacing lead failure compared to
      increased pacemaker clinic surveillance. Since the Medtronic safety alerts on the
      4012, 4082, and 4004 leads, we have followed 261 patients by serial AECG and 165
      patients by increased pacemaker clinic surveillance. Lead failures were
      identified in 75 patients: 68 in the AECG group (31%) and 7 in the clinic group
      (4%, P < 0.001). Repeat AECG confirmed the lead failure in 38 (97%) of 39
      patients in which it could be done. Pacing lead failure documented by AECG could
      be confirmed by a subsequent clinic assessment in only 15 (25%) of 60 patients
      evaluated (P < 0.001). The actuarial survival of the 4012 lead was significantly
      lower in the AECG group compared to the clinic group (56% vs 87% survival at 8
      years, P < 0.002). Similar trends were observed for the 4082 and 4004 leads. AECG
      is a more sensitive method of surveillance for pacemaker lead function compared
      to pacemaker clinic assessment. AECG should be incorporated into the routine
      follow-up of pacemaker patients.

PMID- 9170128
TI  - Predictors of permanence of successful radiofrequency lesions created with
      controlled catheter tip temperature.
AB  - Transient interruption of accessory pathway (AP) conduction is often encountered
      during creation of RF lesions, with return of conduction after seconds to weeks.
      Maximum catheter tip temperature (Tmax) has not been shown to be a good predictor
      of successful RF ablation. However, other indices related to catheter tip
      temperature (T) may predict permanent AP interruption. Ninety-one successful RF
      applications in 58 patients (mean age 11.9 +/- 5.5 years, 38 WPW syndrome, 18
      concealed AP, 2 both) were reviewed retrospectively. Forty-two RF applications
      were transiently successful, with a median time of AP conduction recurrence of
      120 seconds (sec; range, 1 sec to > 1 day). This group was compared with 49
      permanently successful RF applications. T was measured and controlled using the
      Medtronic Atakr system (San Jose, CA, USA). RF lesion duration, power output,
      Tmax and time to Tmax (tmax) were not significantly different between the two
      groups. By univariate analysis, each of the following indices was able to
      discriminate between the transient and permanent lesions, and highly correlated
      with one another, T at the moment of AP interruption (Tsucc; transient 55.0 +/-
      7.9 degrees C vs permanent 49.8 +/- 7.7 degrees C, P = 0.0025), time to success
      (tsucc; transient 4.0 +/- 3.0 sec vs permanent 1.8 +/- 1.3 sec, P = 0.0001),
      ratio of Tsucc/Tmax (transient 0.76 +/- 0.23 vs permanent 0.57 +/- 0.27, P =
      0.0007) and ratio of tsucc/tmax (transient 0.91 +/- 0.69 vs permanent 0.41 +/-
      0.41, P = 0.0001). By logistic regression analysis, no single variable or
      combination of variables was superior to tsucc for prediction of outcome, with a
      breakpoint of 2.3 seconds having a sensitivity of 74% and a specificity of 65%.
      During temperature controlled RF application, indices of time and temperature
      were well-correlated with permanent elimination of AP conduction. Time to
      interruption of AP conduction < 2.3 seconds after the onset of RF application was
      predictive of the permanence of successful RF applications. Known relations
      between RF lesion volume and catheter tip temperature suggest that early
      conduction block may be an indicator of anatomical proximity of the catheter tip
      and the AP. These data suggest that, in conjunction with electrogram criteria,
      selection criteria for optimal sites for RF, application may continue to be
      refined after the onset of RF application, and support the practice of
      terminating RF application if AP conduction is not rapidly interrupted.

PMID- 9170129
TI  - An up-down Bayesian, defibrillation efficacy estimator.
AB  - In both the clinic and the laboratory, efficacy estimators are used to estimate
      the shock strength required to achieve a given defibrillation success rate. In
      the clinic, efficacy estimators are used to estimate highly effective doses
      (i.e., the shock strength that defibrillates 95% of the time), in order to choose
      the setting for an ICD. Efficacy estimators are used in the laboratory to compare
      defibrillation techniques and configurations. Current efficacy estimators are
      inadequate because they are either difficult to use, can only estimate the shock
      strength that defibrillates 50% of the time, or do not yield desirable accuracy
      (low RMS error). This article presents a Bayesian estimation technique that
      forces the difference between successive test shock strengths (step-size) to be a
      fixed value after each measurement. Constraining the difference dramatically
      reduces the computational complexity of the up-down Bayesian method. This new, up
      down Bayesian protocol can be used with up to 15 measurements to estimate the
      shock strength for any given success rate. Simulations show that the added
      constraint (fixed step-size) only slightly increases the rms error, as compared
      to the optimum Bayesian protocol. Our simulations also show that protocols can be
      generated for shock strengths rounded to the nearest 1, 10, or 50 V. without a
      great increase in RMS error. Experimental results from a subset of all the
      simulations are reported from six animals, showing a < -2.4% difference between
      the simulated and measured errors.

PMID- 9170130
TI  - Dual sensor pacemakers in children: what is the choice of sensor blending?
AB  - Dual sensor pacemakers were developed to obtain more appropriate responses to
      activity. We evaluated ten children with dual sensor pacemakers in different
      sensor blending circumstances using exercise testing to assess which ratio was
      optimal. Ten patients with several bradydysrhythmias (ages 6-16 years; mean 10.1
      years) were included in the study. Eight patients had VVIR pacemakers (Vitatron
      Topaz), models and two patients had VDD pacemakers implanted via the transvenous
      route. All patients were in a paced rhythm (98.5% pacing). Accurate T wave
      sensing ranged from 81%-100%; mean 92%, median 95%. Voluntary exercise testing
      with a CAEP protocol was performed using a treadmill with the pacemaker in VVIR
      mode. Medium activity threshold with three sensor blending ratios (QT = ACT, QT >
      ACT, and QT < ACT) were done in all patients. The mean duration of exercise was
      not statistically different among the three sensor blending ratios. After 90
      seconds of exercise, the mean pacing rate had increased by 12%, 3%, and 5%,
      respectively, in the three groups. At maximal exercise, the increases were 45%,
      42%, and 54%. Mean HRs during exercise in each of the three ratios were not
      significantly different, although we found a statistically significant increase
      in HR during the first two stages of rest period in the QT = ACT sensor blending
      ratio compared to the QT > ACT ratio. No difference was observed after the second
      stage. IN CONCLUSION: (1) there is no difference between the QT = ACT, QT < ACT,
      and QT > ACT sensor blending ratios; and (2) each child has to be evaluated by
      exercise testing to program a correct sensor blending ratio.

PMID- 9170131
TI  - Long-term survival and complications in patients with malignant ventricular
      tachyarrhythmias: treatment with a nonthoracotomy implantable cardioverter
      defibrillator with or without a subcutaneous patch.
AB  - The Endotak lead system and ICD has been used to treat patients with malignant
      ventricular arrhythmias. We analyzed the clinical characteristics of 1,053
      patients who underwent implantation of the Endotak lead system with or without a
      subcutaneous patch. Group A consisted of 567 patients receiving the Endotak lead
      with a subcutaneous patch; group B consisted of 486 patients receiving the
      Endotak lead alone. The 2-year survivals from sudden death, cardiac death, and
      total death in groups A and B were 97.6%/98.2% (P = 0.38), 88.6%/92.7% (P =
      0.09), and 84.7%/86.8% (P = 0.06), respectively. Minimum tested effective
      defibrillation energy at implantation was 17.2 +/- 5.2 J for group A and 15.8 +/-
      5.1 J for group B (P < 0.01). The operative mortality was 1.8% in group A and
      0.6% in group B (P = 0.09). The incidence of lead dislodgment, malfunction, and
      infection was 6.7% for group A and 3.5% for group B (P < 0.01). Sudden death
      survival was excellent in both groups with less lead complications in group B.
      The Endotak lead alone may be the preferred choice of lead configuration in those
      patients who have adequate defibrillation thresholds at implant.

PMID- 9170133
TI  - Atrial electrophysiological features in patients with Wolff-Parkinson-White and
      atrial fibrillation: absence of rate adaptation of intraatrial conduction time
      parameters.
AB  - Clinical electrophysiology has not yet clearly defined atrial features that can
      predict spontaneous occurrence of atrial fibrillation (AF). The aim of this work
      was to identify atrial electrophysiological features that can distinguish Wolff
      Parkinson-White patients with spontaneous AF from those without this arrhythmia.
      Sixty-nine patients with Wolff-Parkinson-White were divided into three groups:
      group I (16 patients) with spontaneous AF; group II (35 patients) with
      reciprocating tachycardia but not AF; and group III (18 patients) asymptomatic
      without documented arrhythmias. Atrial effective refractory periods (ERPs) and
      intraatrial conduction times in response to premature extrastimuli were analyzed.
      The latter were evaluated as the A1A2 interval minus the correspondent S1S2
      interval (A1A2-S1S2), S1A2 and the interval A1A2 following the shortest S1S2
      producing atrial activation (FRP'). All the parameters have been evaluated in two
      atrial sites and at two atrial pacing cycle lengths (600 and 400 ms). For all the
      parameters, the difference ("gradient") was calculated between the values of the
      same parameter measured at the atrial pacing cycle length of 600 ms and that
      found at the atrial pacing cycle length of 400 ms in the same recording site in
      each patient was calculated. Atrial ERP did not differ significantly in the three
      groups. Intraatrial conduction parameters, evaluated in the high right atrium
      (HRA), were longer when measured at an atrial pacing of 400 ms and showed a lack
      of rate adaptation in patients with spontaneous AF. In group I patients in
      particular, FRP' became longer with the increase of atrial rate, while in groups
      2 and 3, it usually shortened. The mean gradient of HRA FRP' was -15.0 +/- 19 ms
      in group I as compared to 5.7 +/- 13 ms in group II and 6.4 +/- 13 ms in group
      III (P < 0.001); sensitivity, specificity, and negative predictive value of a
      negative gradient in the identification of patients with spontaneous AF, were,
      respectively, 83%, 75%, and 93%. Patients from groups 2 and 3 did not differ in
      any of the analyzed parameters. Patients with Wolff-Parkinson-White and
      spontaneous AF showed prolonged intraatrial conduction times and a different
      behavior in response to modification of heart rate.

PMID- 9170132
TI  - The ongoing influence of staff training on the performance of radiofrequency
      catheter ablation.
AB  - The aim of this study was to assess whether the performance of RF catheter
      ablations continues to improve by further staff training once an initial success
      rate of > 90% has been achieved. Two hundred and ninety-five procedures of SVT
      catheter ablation using RF energy were studied. Atrial tachycardia and atrial
      flutter substrate ablations were not included. The procedures were performed
      during a 4-year period by the same physician and nurse, who had previous training
      in these procedures. The 4-year period was subdivided into four consecutive 1
      year periods in which 69, 72, 68, and 86 procedures were performed. The outcome,
      recurrence rate, and duration of the curative procedure were compared among the
      four periods. There was no significant difference in the initial success rate
      among the four periods. The recurrence rate decreased from 21.74% to 13.95% (P <
      0.05). The duration of the curative procedure decreased from 93.7 +/- 78.4
      minutes to 39.1 +/- 32.2 minutes (P < 0.001), and the fluoroscopic time decreased
      from 25.5 +/- 22.3 minutes to 11.3 +/- 8.2 minutes (P < 0.001). These results
      were similar when accessory pathway and selective AV nodal pathways ablations
      were separately evaluated. Following the initial staff training, during which the
      expected 80%-90% success rate is achieved, additional training will reduce the
      recurrence rate and the duration of the procedures at a similar level of success.

PMID- 9170134
TI  - Inappropriate management of self-terminating ventricular arrhythmias by
      implantable cardioverter defibrillators despite a specific reconfirmation
      algorithm: a report of two cases.
AB  - Algorithms that attempt to reconfirm the presence of an arrhythmia prior to
      definite treatment have been implemented in ICDs to prevent inappropriate shock
      therapy due to self-terminating ventricular arrhythmias. Nevertheless, in two
      patients, clinically inappropriate shocks were delivered after spontaneous
      conversion of the arrhythmia despite the use of a specific reconfirmation
      algorithm. Reconfirmation criteria were met due to a premature ventricular
      complex causing a short cycle in the first patient and a long postextrasystolic
      pause in the second patient. To avoid inappropriate shock therapy due to self
      terminating ventricular arrhythmias, further improvement of detection algorithms
      is required.

PMID- 9170135
TI  - Autonomic nervous system activity during tilt testing in syncopal patients,
      estimated by power spectral analysis of heart rate variability.
AB  - Spectral analysis of heart rate variability (HRV) was used to assess changes in
      autonomic function before and during postural tilt in 28 syncopal patients: 14
      (group A) with positive and 14 (group B) with negative tilting test, and 14
      normal controls (group C). Frequency-domain measurements of the high (HF) and low
      (LF) frequency bands and the ratio LF/HF were derived from Holter recordings,
      computed by Fast Fourier analysis for 4-minute intervals immediately before tilt
      testing, immediately after tilting, and just before the end of the test. In group
      A, the mean values of LF and HF decreased slightly in response to tilting while
      the LF/HF ratio increased, though these changes were not statistically
      significant. All parameters showed a statistically significant increase just
      before the onset of syncope. In group B, there were no significant changes in the
      parameters measured throughout the test. In group C, there was an increase in the
      LF and LF/HF ratio and a decrease in the HF immediately after tilting. There were
      no further significant changes in any of the parameters during the test. Syncopal
      patients have a different pattern of response to the orthostatic stimulus, in
      that they do not show the increase in sympathetic tone observed in normal
      individuals immediately after tilting. In the patients with a positive tilt test,
      there is a shift in the balance of ANS activity towards the sympathetic system
      shortly before the onset of syncope.

PMID- 9170136
TI  - Quantitative analysis of concealed conduction into accessory atrioventricular
      pathways in Wolff-Parkinson-White syndrome.
AB  - Concealed conduction is demonstrated to occur in an accessory AV pathway (AP). To
      test the hypothesis that anterograde and retrograde concealed conduction in the
      AP would have different characteristics, 35 consecutive patients with single APs
      were studied. The anterograde or retrograde ERP of the AP could be determined in
      23 of those patients. Anterograde concealed conduction in the AP was assessed in
      the first 13 patients with retrograde AP conduction (6 APs with retrograde
      conduction only and 5 with both directions) (group A). Retrograde concealed
      conduction in the AP was evaluated in the remaining 10 patients with anterograde
      AP conduction (6 APs with anterograde conduction only and 4 with both directions)
      (group B). The concealed conduction in the AP was quantified by determining the
      ERP of the AP using a "probe" extrastimulus (Sp) introduced in the opposite
      chamber. The ERP was determined both during conventional extrastimulus (S1S2
      method; ERPc) and during that with an Sp (S1SpS2 method; ERPp). The Sp was
      delivered before or after the last S1 with various S1Sp intervals. The ERPp was
      determined at each S1Sp interval. Three distinct patterns in concealed conduction
      in the AP were noted. In the first pattern, the ERPp was always shorter than the
      ERPc, whereas the reverse relation was noted in the second pattern. The third
      pattern showed a combination of the two. In group A, only the first pattern was
      noted. In group B, the first, second, and third patterns were noted in 4, 2, and
      4 patients, respectively. The first pattern was noted only in septal APs and the
      second and third were seen only in left free-wall APs. The second pattern was
      seen in patients with retrograde AP conduction, whereas the third one was mainly
      noted in patients without retrograde AP conduction. These observations indicate
      that anterograde and retrograde concealed conduction in the AP have different
      characteristics. Shortening of the ERPp might be due to the "peeling back"
      phenomenon, and its lengthening might be caused by the presence of the
      inhomogeneous refractory periods of the AP.

PMID- 9170137
TI  - Toward optimizing a preshaped catheter and system parameters to achieve single
      lead DDD pacing.
AB  - P wave electrogram amplitudes and atrial stimulation thresholds were determined
      in eight Hanford miniature swine using a preshaped catheter with an "S" curve in
      the SVC, and a major lobe in the atrium to enhance electrode contact with the
      atrial wall. The catheter was designed for pacing and sensing in the DDD mode. P
      wave amplitudes were also ascertained with two commercially available VDD leads
      and compared to the data from the experimental catheters. The preshaped catheter
      used two 6-mm2 platinum iridium atrial electrodes with a 7-mm separation. Both
      atrial electrodes are on the same side of the catheter, facing outward on the
      major atrial lobe formed in the catheter. The P wave amplitudes were tested only
      in the differential bipolar configuration. For the eight preshaped catheters, the
      mean was 6.6 +/- 3.8 mV while for the conventional leads it was 2.9 +/- 1.6 mV.
      The mean atrial stimulation thresholds ranged from 1.1 +/- 0.2 V to 2.3 +/- 1.2
      V, with still lower thresholds of 0.9-1.3 V when using the parallel unipolar
      atrial electrode configuration, in which both parts of the bipolar atrial
      electrode are configured as a unipolar electrode. The data suggest that bipolar
      simulation may be effective if sequential reverse polarity pulses are used to
      achieve cathodal stimulation from each electrode of the bipolar pair, on a beat
      to-beat basis.

PMID- 9170138
TI  - A useful marker during ablation.

PMID- 9170139
TI  - Dissimilar right atrial rhythms: a case report.
AB  - Dissimilar atrial rhythms are generally defined by the coexistence of atrial
      fibrillation in one atrium and a more regular rhythm in the other atrium, and are
      reported with left atrial enlargement and/or digitalis toxicity. We report a
      unique case of dissimilar atrial rhythms controlling two different parts of the
      same atrium without interfering with one another. The mechanism of the
      dissociation of two foci is not clear; however, scarring due to previous surgery
      remains a possibility.

PMID- 9170140
TI  - Surgical interruption of a left inferior vena cava following the transfemoral
      implantation of a permanent pacing lead.
AB  - This report describes the case of a patient in whom, after an unsuccessful
      attempt through the subclavian vein, a permanent pacing lead was inserted through
      the femoral vein and a left inferior vena cava with azygos continuation. The
      procedure was followed 4 months later by a pulmonary embolism complicating a
      right femoroiliac thrombosis. The patient was successfully treated by a
      percutaneous lead extraction procedure combined with an inferior vena caval
      surgical interruption.

PMID- 9170141
TI  - Accidental atrial and ventricular stimulation by pacemaker event marker.
AB  - A case of both atrial and ventricular stimulation by the sense event marker
      during external chest wall stimulation of a DDDR pacemaker is reported. This
      unusual phenomenon might produce pacemaker-mediated tachycardia.

PMID- 9170142
TI  - High dose neostigmine treatment of malignant sinus tachycardia.
AB  - Sinus tachycardia caused by circulating catecholamines in the setting of
      congestive heart failure may impair systemic perfusion because of decreased
      diastolic filling time. We report the case of a patient with Wolff-Parkinson
      White syndrome with angina and cardiogenic shock who improved dramatically
      following administration of neostigmine. Cardiac output, blood pressure, and
      stroke volume increased as heart rate was reduced. A previous attempt at heart
      rate control, in the same patient, using a low dose beta-antagonist, precipitated
      hemodynamic collapse. The remarkable recovery of our patient suggests that
      acetylcholinesterase inhibitors may warrant further investigation in patients
      with severe sinus tachycardia.

PMID- 9170143
TI  - Is this the natural history of the retention wire? A case report.
AB  - We report on a 71-year-old man who had a dual chamber pacemaker implanted in
      1991. A Class IV fracture of the Telectronics Accufix 330-801 atrial lead was
      observed on a chest X ray in December 1993. Serial chest X ray and fluoroscopy
      documented stable position of the migrated fractured J wire. The patient remained
      asymptomatic and a decision for conservative monitoring was made. A subsequent
      finding of a right atrial mass on echocardiography and evidence of pulmonary
      embolism on lung scan prompted a change of strategy. The patient underwent
      atriotomy, and a right atrial thrombus was discovered associated with the
      fractured J retention wire, both of which were extracted uneventfully. This case
      is illustrative that despite apparent stability of a Class IV fracture, it may
      result in endothelial injury with a thrombogenic nidus and resultant
      complications.

PMID- 9170144
TI  - Electrostimulated cardiomyoplasty: from experimental to clinical studies.

PMID- 9170145
TI  - Tryptamine: a possible endogenous substrate for CYP2D6.
AB  - The fact that CYP2D6 is not only expressed in liver but also in brain and the
      clinical association of this cytochrome with Parkinson's disease suggests the
      possibility of existence of some endogenous substrate, and among these perhaps
      one or more neurotransmitters could be metabolized by CYP2D6. In this study we
      explored such a possibility by studying the modulation of CYP2D6 activity by
      several neurotransmitters. Our findings confirm the occurrence of a competitive
      inhibition of dextromethorphan O-demethylation in the presence of tryptamine,
      with a Ki value of 44.6 microM. Tryptamine was metabolized in human liver
      microsomes by an enzyme activity with a K(m) of 3.6 +/- 0.9 microM. Such activity
      is NADPH dependent and is inhibited by quinidine and CYP2D6-specific substrates.
      The product of the reaction is tryptophol. These results suggest that tryptamine
      may be an endogenous substrate of CYP2D6.

PMID- 9170146
TI  - Human Ah receptor (AHR) gene: localization to 7p15 and suggestive correlation of
      polymorphism with CYP1A1 inducibility.
AB  - The mammalian aromatic hydrocarbon receptor (AHR) is a ubiquitous ligand
      activated transcription factor. AHR ligands include 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD; dioxin), benzo[a]pyrene, and polychlorinated and polybrominated
      biphenyls; the endogenous ligand is not yet known. Following ligand binding, the
      AHR transcriptionally activates genes encoding drug-metabolizing enzymes
      important in both the metabolic potentiation of substrates to genotoxic reactive
      intermediates and ultimate carcinogens, and the detoxification of toxic or
      carcinogenic drugs and other environmental pollutants. AHR-mediated gene
      expression is also involved in many critical life processes (e.g. cell type
      specific differentiation, cell division, apoptosis) by signal transduction
      mechanisms. Similar to mice, human populations exhibit a > 20-fold range of the
      CYP1A1 inducibility/AHR affinity phenotype. In the present study, we localized
      the human AHR gene to chromosome 7p15, using fluorescence in situ hybridization
      (FISH). Performing linkage analysis in a three-generation family, we show with
      good probability that the high CYP1A1 inducibility phenotype segregates with the
      7p15 region. Sequencing 93 nt (31 amino acids) of the human AHR gene's exon 9,
      which is the region correlated with the mouse A375V polymorphism responsible for
      the major portion of high vs low CYP1A1 inducibility/AHR affinity, we found no
      nucleotide differences; Val-381 was present in all five individuals examined
      (four related and one unrelated), two of whom show "high' and three of whom show
      "low' CYP1A1 inducibility. These data indicate that the "high' and "low' CYP1A1
      inducibility trait, in the population studied, cannot be explained by a
      difference among these 31 amino acids in exon 9 of the AHR gene.

PMID- 9170147
TI  - Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl
      hydroxylation and S-mephenytoin 4'-hydroxylation activities in livers of Japanese
      and Caucasian populations.
AB  - Genomic DNA was isolated from livers of 39 Japanese and 45 Caucasians and the
      genotypes of CYP2C9 and 2C19 genes were determined with PCR methods using
      synthetic oligonucleotide primers. Liver microsomes were also prepared from these
      human samples and activities for tolbutamide methyl hydroxylation and S
      mephenytoin 4'-hydroxylation were determined. The single base mutation of C416T
      (Arg144Cys) in CYP2C9 was detected in 22% of Caucasians but not in Japanese
      samples. Another single base mutation at A1061C (Ile359Leu) in the CYP2C9 gene
      was found with frequencies of about 8% in both races. We did not detect any
      individuals who have either homozygous Cys144/Cys144 or Leu359/Leu359 CYP2C9
      variant nor both heterozygous Cys144-Ile359 and Arg144-Leu359 CYP2C9 variant in
      the human samples examined. The CYP2C19m2 genetic polymorphism was found only in
      Japanese people, while CYP2C19m1 type was determined in both races, with higher
      incidence in Japanese than in Caucasian population. Immunoblotting analysis of
      human liver microsomes suggested that CYP2C9 is a major component of the human
      CYP2C enzyme pool; it accounted for approximately 20% of total P450 in liver
      microsomes of both human populations. The levels of CYP2C19 protein were
      determined to be about 0.8% and 1.4% of total P450 (mean) in Japanese and
      Caucasians, respectively. We did not detect CYP2C19 protein in liver microsomes
      of humans who were genotyped for CYP2C19 gene as m1/m1, m1/m2, and m2/m2 variants
      but detected CYP2C9 protein in all of the samples examined. Good correlations
      were found between levels of CYP2C9 and activities of tolbutamide methyl
      hydroxylation (r = 0.77) and between levels of CYP2C19 and activities of S
      mephenytoin 4'-hydroxylation (r = 0.86) in liver microsomes of the human samples
      examined. Tolbutamide methyl hydroxylation activities were lower in human samples
      with the Leu359 allele of CYP2C9 than those with the Cys144 allele and wild-type
      (Arg144-Ile359); the former type showed slightly higher K(m) values. When
      calculated on P450 basis, liver microsomes of individuals having m1/m1, m1/m2,
      and m2/m2 types of CYP2C19 had very low catalytic activities for S-mephenytoin 4'
      hydroxylation. These results provide useful comparisons for pharmacokinetic and
      toxicokinetic models of some of the clinically used drugs that are oxidized by
      CYP2C proteins in humans.

PMID- 9170148
TI  - Evidence for the effect of gender on activity of (S)-mephenytoin 4'-hydroxylase
      (CYP2C19) in a Chinese population.
AB  - There is evidence that the sex-dependent expression of individual forms of the
      human cytochrome P450s (CYPs) results in gender-related differences in the
      hepatic metabolism of certain drugs. Previous work has shown that conflicting
      evidence exists relating to the sex differences in the activity of (S)
      mephenytoin 4'-hydroxylase (CYP2C19). Accordingly, we assessed the effect of
      gender on CYP2C19 activity in a phenotyped and genotyped healthy unrelated
      Chinese population for further evidence of such a gender-based differentiation.
      One hundred and sixteen females and 129 males took one tablet of 100 mg racemic
      mephenytoin (Mesantoin, Sandoz) after emptying their urinary bladders. Amounts of
      (S)- and (R)-mephenytoin and its metabolite 4'-hydroxymephenytoin (4'-OH-M)
      excreted in the postdose 0-8 h urine collection were determined by GC and HPLC
      methods, respectively. The CYP2C19 activity was expressed as the ratio of S/R
      mephenytoin (S/R-ratio), the percentage of the dose excreted as 4'-OH-M (D%), and
      the log10 of the hydroxylation index which was defined as the ratio of micromoles
      of (S)-mephenytoin dose to micromoles of 4'-OH-M excreted in urine (1g HI). From
      all the subjects studied, 53 extensive metabolizers (EMs) and 19 poor
      metabolizers (PMs) phenotyped were randomly selected and the DNA extracted from
      their blood samples was utilized for genotyping analysis according to the
      previously developed standard procedures. In this population, the phenotype PMs
      were identified in 10.9% (14/128) of the males, as compared with 11.2% (13/116)
      of the females (chi 2 = 0.0045, df = 1; p > 0.05). In all phenotyped subjects,
      the S/R-ratio of EM males was significantly higher than that of EM females (mean
      +/- SD; 0.28 +/- 0.17 vs. 0.24 +/- 0.15; p = 0.030), but no sexual
      differentiation was observed (p > 0.05) in 4'-OH-M excreted among all EMs and
      PMs, or the S/R-ratio among all PMs. In all genotyped EMs, the frequency of
      homozygous EMs was 18.4% higher in females (51.7%, 15/29) than in males (33.3%,
      8/24) although there was no significant difference (chi 2 = 1.1370, df = 1, p >
      0.05), but the S/R-ratio was lower in homozygous females than in homozygous males
      (0.22 +/- 0.14 vs. 0.33 +/- 0.09; p = 0.046). Thus, we conclude that the higher
      CYP2C19 activity in females exists among both the phenotyped EMs and the
      genotyped homozygous EMs compared with that in males, and that the defect
      frequency of the enzyme activity is equal between the genders. We also conclude
      that the S/R-ratio is more a sensitive metabolic marker of CYP2C19 enzyme
      activity than the D% and 1g HI.

PMID- 9170149
TI  - Localization of polymorphic N-acetyltransferase (NAT2) in tissues of inbred mice.
AB  - Like humans, mice exhibit polymorphism in the N-acetylation of aromatic amines,
      many of which are toxic and/or carcinogenic. Mice have three N-acetyltransferase
      (Nat) genes, Nat1, Nat2 and Nat3, and Nat2 is known to be polymorphic. There is a
      dramatic difference in the acetylation of NAT2 substrates by blood from fast
      (C57BL/6J) compared with slow acetylator (A/J) mice. However, the acetylation of
      these substrates by liver cytosols from the two strains is very similar. In order
      to determine whether the expression of the NAT2 protein corresponded with the
      activities measured, a polyclonal antipeptide antisera was raised against the C
      terminal decapeptide of NAT2 and characterized using recombinant murine NAT2
      antigen. Enzyme-linked immunosorbent assays (ELISAs) demonstrated that the anti
      NAT2 antiserum bound in a concentration-dependent fashion to recombinant NAT2.
      Immunochemical analysis of mouse liver cytosols from C57BL/6J or A/J livers
      indicated that the level of NAT2 protein expressed in the two strains was
      similar. Immunohistochemical staining of C57BL/6J liver with anti-NAT2 antiserum
      showed that NAT2 was expressed in hepatocytes throughout the liver although the
      intensity of staining in the perivenous (centrilobular) region was higher than
      that in the periportal region. NAT2 was also detected in epithelial cells in the
      lung, kidney, bladder, small intestine and skin as well as in erythrocytes and
      lymphocytes in the spleen and hair follicles and sebaceous glands in the skin.
      Characterization of the distribution of NAT2 will be of value in elucidating the
      role of polymorphic N-acetylation in protecting the organism from environmental
      insults as well as in endogenous metabolism.

PMID- 9170150
TI  - NAT2 genotyping and efficacy of sulfasalazine in patients with chronic discoid
      lupus erythematosus.
AB  - Sulfasalazine is an effective agent for chronic discoid lupus erythematosus
      (CDLE) but the response to treatment is considerably variable between patients
      and is also unpredictable. The reason for this might relate to differences in
      metabolism of the drug which is extensively acetylated by the polymorphic enzyme
      N-acetyltransferase 2 (NAT2). To test this possibility, the N-acetylation
      phenotype of eleven patients with CDLE and treated by standard doses of
      sulfasalazine was retrospectively determined by genotyping. A clear-cut
      difference in the outcome of treatment was observed according to whether the
      patients were slow acetylators (SA) or rapid acetylators (RA). Eight out of 11
      patients responded to treatment with a complete or marked remission of the
      disease. Seven of them were RA. The three other patients who did not respond at
      all to the drug were SA. In addition, SA seem to be more prone to toxic events.
      These findings strongly suggest that the genetic polymorphism of NAT2 is
      responsible for differences in the response to sulfasalazine in patients with
      CDLE. Therefore, candidates for sulfasalazine therapy should be genotyped to
      identify those patients who might benefit from the drug.

PMID- 9170151
TI  - Paraoxonase (PON1) gene in mice: sequencing, chromosomal localization and
      developmental expression.
AB  - Serum paraoxonase hydrolyses the toxic metabolites of several organophosphorus
      insecticides, as well as the nerve agents soman and sarin. We have previously
      shown that elevated serum paraoxonase levels protect mice against organophosphate
      toxicity. In the present study, we determined the cDNA sequence and chromosomal
      location of the mouse paraoxonase gene, as well as its developmental expression
      in mice and rats. The mouse cDNA encodes a protein of 355 amino acids and shows
      81% identity with the human sequence. In situ hybridization demonstrated that the
      mouse paraoxonase gene maps to chromosome 6, a region conserved with the
      paraoxonase region of chromosome 7q21-22 in humans. Serum paraoxonase activities
      toward three substrates, paraoxon, chlorpyrifos-oxon and diazoxon, were very low
      at birth and increased with age reaching adult levels at 20 days in mice and 25
      days in rats. The increase of serum paraoxonase activity in developing animals
      correlates well with the increased resistance to organophosphate poisoning that
      has been reported in previous studies.

PMID- 9170152
TI  - CYP2D6 phenotype and genotype in a Canadian Native Indian population.

PMID- 9170153
TI  - Characterization of the 16+9 kb and 30+9 kb CYP2D6 XbaI haplotypes.

PMID- 9170154
TI  - UGT1*1 genotyping in a Canadian Inuit population.

PMID- 9170155
TI  - Lung cancer risk in relation to mephenytoin hydroxylation activity.

PMID- 9170156
TI  - Lack of correlation between phenotype and genotype for the polymorphically
      expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in
      pyrimidine catabolism. DPD deficiency is associated with an increased risk of
      toxicity in cancer patients receiving 5-fluorouracil (5-PU) treatment. DPD
      deficiency causes an inborn error of metabolism called thymine-uraciluria that is
      in some instances associated with convulsive disorders and developmental delay in
      children. We have studied the molecular mechanism accounting for DPD deficiency
      in a Pakistani pedigree having 2-year-old child with thymine-uraciluria and
      exhibiting some degree of motor impairment and developmental delay. A common
      splice mutation was found in the patient's dihydropyrimidine dehydrogenase (DPYD)
      gene that produces a mutant mRNA resulting in the complete lack of DPD protein
      and activity in lymphocytes and primary fibroblast. This trait segregated in the
      family following a typical Mendelian distribution. Surprisingly, the patient's
      brother also had thymine-uraciluria and was homozygous for the splicing mutation
      but was clinically asymptomatic. Sequence tagged sites (STS) linkage analyses
      within 5 megabases of telomeric and centromeric DNA surrounding the DPYD gene
      revealed no allelic polymorphism between the two brothers. These results suggest
      that DPD deficiency might not be the only cause of the more severe clinical
      phenotypes observed in certain thymine-uraciluria patients and that an incomplete
      correlation between phenotype and genotype is present in the population.

PMID- 9170157
TI  - Pigment cell research: what directions?
AB  - Over the past few years, pigment cell research has experienced unprecedented
      impetus in practically all areas. However, as is usually the case in periods of
      rapid development, several critical issues buried under the glitz of recent
      success are more or less the same as they have been for many years. Persisting
      misconceptions and scientific prejudices also contribute to cloud many issues. It
      appears, for example, that the common perception of melanocyte function is still
      biased by the traditional concept of a pigment producing cell. In fact, in
      addition to melanin, epidermal melanocytes are known to produce and excrete a
      number of melanin-related metabolites, such as DHI and DHICA, which appear to
      play a critical role in protection of epidermal tissues against toxic oxygen
      radical species as well as in inflammatory and immune reactions. Another major
      gap concerns the pheomelanin pigmentary system. This has traditionally been a
      neglected area of research in spite of compelling evidence for the abnormal
      susceptibility of red heads to sun damage and skin cancer. An increased attention
      to the peculiar biological and biochemical features of the pheomelanin forming
      cells will expectedly open new vistas on the UV susceptibility trait and the
      etiology of melanoma.

PMID- 9170158
TI  - Molecular basis of congenital hypopigmentary disorders in humans: a review.
AB  - Many specific gene products are sequentially made and utilized by the melanocyte
      as it emigrates from its embryonic origin, migrates into specific target sites,
      synthesizes melanin(s) within a specialized organelle, transfers pigment granules
      to neighboring cells, and responds to various exogenous cues. A mutation in many
      of the respective encoding genes can disrupt this process of melanogenesis and
      can result in hypopigmentary disorders. Following are examples highlighting this
      scenario. A subset of neural crest derived cells emigrate from the dorsal surface
      of the neural tube, become committed to the melanoblast lineage, and are targeted
      along the dorsal lateral pathway. The specific transcription factors PAX3 and
      MITF (microphthalmia transcription factor) appear to play a regulatory role in
      early embryonic development of the pigment system and in associated diseases (the
      Waardenburg syndromes). During the subsequent development and commitment of the
      melanoblast, concomitant expression of the receptors for fibroblasts growth
      factor (FGFR2), endothelin-B (EDNRB), and steel factor (cKIT) also appears
      essential for the continued survival of migrating melanoblasts. Lack or
      dysfunction of these receptors result in Apert syndrome, Hirschsprung syndrome
      and piebaldism, respectively. Once the melanocyte resides in its target tissue, a
      plethora of melanocyte specific enzymes and structural proteins are coordinately
      expressed to form the melanosome and to convert tyrosine to melanin within it.
      Mutations in the genes encoding these proteins results in a family of congenital
      hypopigmentary diseases called oculocutaneous albinism (OCA). The tyrosinase gene
      family of proteins (tyrosinase, TRP1, and TRP2) regulate the type of eumelanin
      synthesized and mutations affecting them result in OCA1, OCA3, and slaty (in the
      murine system), respectively. The P protein, with 12 transmembrane domains
      localized to the melanosome, has no assigned function as of yet but is
      responsible for OCA2 when dysfunctional. There are other genetically based
      syndromes, phenotypically resembling albinism, in which the synthesis of
      pigmented melanosomes, as well as specialized organelles of other cell types, is
      compromised. The Hermansky-Pudlak syndrome (HPS) and the Chediak-Higashi syndrome
      (CHS) are two such disorders. Eventually, the functional melanocyte must be
      maintained in the tissue throughout life. In some cases it is lost either
      normally or prematurely. White hair results in the absence of melanocytes
      repopulating the germinative hair follicle during subsequent anagen stages.
      Vitiligo, in contrast, results from the destruction and removal of the melanocyte
      in the epidermis and mucous membranes.

PMID- 9170159
TI  - Evidence to suggest that expression of MITF induces melanocyte differentiation
      and haploinsufficiency of MITF causes Waardenburg syndrome type 2A.
AB  - MITF (microphthalmia-associated transcription factor) encodes a transcription
      factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif. Ectopic
      expression of MITF is found to convert NIH/3T3 fibroblasts into cells with
      characteristics of melanocytes. MITF transfectants formed foci, which
      superficially resembled those induced by oncogenes, but did not exhibit malignant
      phenotypes. Instead, they contained dendritic cells that express melanogenic
      marker proteins such as tyrosinase and tyrosinase-related protein 1. Such
      properties were not observed in cells transfected with the closely related gene,
      TFE3. These findings indicated that MITF is involved in melanocyte
      differentiation. Two mutations (C760-->T and C895-->T) in MITF are found to be
      associated with individuals with Waardenburg syndrome type 2 (WS2). These
      mutations create stop codons in exon 7 and 8, respectively, and probably result
      in truncated proteins lacking HLH-Zip or Zip structure. To understand how these
      MITF mutations cause WS2 in heterozygotes, mutant MITF proteins were generated
      and used for DNA-binding and luciferase reporter assays. The mutated MITF
      proteins lose their DNA-binding activity and fail to transactivate the promoter
      of the tyrosinase gene. However, these mutated proteins do not appear to
      interfere with the activity of wild-type MITF protein in these assays, indicating
      that they do not show a dominant-negative effect. These findings suggest that the
      phenotypes of the two WS2 families are caused by loss-of-function mutations in
      one of the two MITF alleles, resulting in haploinsufficiency of the MITF protein,
      the transcription factor necessary for normal melanocyte differentiation.

PMID- 9170160
TI  - Signal transduction by the oncogenic receptor tyrosine kinase Xmrk in melanoma
      formation of Xiphophorus.
AB  - Melanoma formation in Xiphophorus is initiated by overexpression of an oncogenic
      version of the EGFR-related receptor tyrosine kinase Xmrk (Xiphophorus melanoma
      receptor kinase). High steady-state levels of Xmrk oncogene mRNA are found in
      malignant melanoma; however, this overabundance of transcripts appears to be not
      sufficient for manifestation of the full oncogenic potential of Xmrk. In
      addition, several amino acid exchanges cause the oncogenic receptor to be highly
      active, resulting in a strong tyrosine phosphorylation even without growth factor
      stimulation. Besides the receptor itself a Xmrk-specific signal transduction
      seems to be a critical part of the transformation machinery. Expression
      experiments in transgenic fish indicate that the Xmrk-mediated intracellular
      signalling is contributing to the cell-type specificity in development of
      hereditary melanoma in Xiphophorus.

PMID- 9170161
TI  - The role of alpha-MSH, its agonists, and C-AMP in in vitro avian melanocytes.
AB  - Little is known about the effect of alpha-MSH and other melanogenic stimulators
      on avian melanocytes. Tissue cultures of Barred Plymouth Rock regenerating
      feather melanocytes were established and the culture medium contained selected
      concentrations of alpha-MSH and other melanogenic stimulators in Ham's F-10
      medium supplemented with antibiotics and 10% new born calf serum. Cultures were
      maintained at 37 degrees C in 95% air/5% CO2. No increase in melanogenesis over
      control levels due to the addition of 10(-5) M Forskolin, 10(-4) M IBMX, 10(-3) M
      c-GMP, and 10(-3) M db-c-AMP was observed in the cultures on days 5 and 7.
      However, 2.5 (optimum), 5, and 10 micrograms/ml alpha-MSH and 10(-3) M 8-bromo-c
      AMP significantly increased melanogenesis over control levels on days 5 and 7.
      The stimulation of melanogenesis was detectable by a significantly increased
      number of melanocytes containing numerous stage IV melanosomes. No increase in
      melanocyte cell number was observed in any of the experimental cultures. The
      addition of 1, 2 (optimum), or 3 mM calcium did enhance the increased
      pigmentation effect of 2.5 micrograms/ml alpha-MSH. Two very convincing
      experiments showed that c-AMP was the second messenger for alpha-MSH in these
      birds. First, the c-AMP inhibitor, 10(-3) M Rp-c-AMPS, completely inhibited the
      stimulatory effect of alpha-MSH in these in vitro melanocytes. Second, direct
      measurements of c-AMP levels in feather tissue showed a significant increase in c
      AMP levels 10.min after alpha-MSH treatment. Controls received no alpha-MSH. The
      results showed that these avian melanocytes have alpha-MSH receptors and were
      able to respond to the hormone. C-AMP was the second messenger in this system.
      Apparently db-c-AMP was not able to enter these mature, highly-differentiated
      cells and c-AMP agonists, Forskolin and IBMX, were also either unable to enter
      these older cells or, if they did enter the cells, were unable to stimulate c-AMP
      production. Evidently the more lipophilic 8-bromo-c-AMP was able to enter these
      cells and stimulate melanogenesis.

PMID- 9170162
TI  - Melanogenesis, tyrosinase expression, and reproductive differentiation in black
      and white truffles (Ascomycotina).
AB  - White and black truffles of the genus Tuber are Ascomycotina as well as
      Neurospora crassa, which expresses tyrosinase dependently on the reproductive
      cycle. Tyrosinase expression dependent on reproductive differentiation has been
      also described in black truffles. We present novel and comparative work on
      melanogenic activities in black and white truffles that both express true
      tyrosinases. L-tyrosine 3-monooxygenase and L-DOPA oxidase activities colocalize
      as histochemically detected and are similarly located in white and black
      truffles, from the hypothecium through the sporogenic hyphae to asci and spores.
      Sulfur components of truffle flavours reversibly inhibit tyrosinase. The
      respiratory phenotype of truffle mitochondria is discussed in relation to
      reproductive differentiation and melanogenesis.

PMID- 9170164
TI  - Proposed reclassification of melanoma: a meeting held at the XVIth International
      Pigment Cell Congress, 3rd November 1996.
AB  - The current classification of cutaneous melanoma was developed in 1972 and
      revised in 1982. Since that time, new concepts and terminology have evolved that
      require consideration of a further revision. Regional meetings of interested
      parties have been held to review the Classification and there will be an open
      meeting on the topic at the 1997, 4th World Conference on Melanoma in Sydney,
      Australia. This paper reports on a meeting to discuss some of the concepts that
      will form part of that process, held on November 3, 1996 as part of the XVIth
      International Pigment Cell Conference. A questionnaire is included that will
      allow the interested reader to provide comments on the topic.

PMID- 9170163
TI  - The influence of extracellular matrix proteins on cutaneous and uveal
      melanocytes.
AB  - Cutaneous and ocular melanocytes are routinely cultured in complex mitogen-rich
      media. The physiological regulation of melanocyte proliferation and
      differentiation is not yet fully defined and this study summarises several
      separate lines of evidence which suggest that, in vivo, some of the signals
      required for melanocyte proliferation and differentiation may derive from
      extracellular matrix (ECM) proteins adjacent to these cells. Culture of cutaneous
      and uveal melanocytes on cell-derived and individual ECM proteins was found to
      influence cell morphology with such effects being most noticeable in mitogen
      deficient media. Similarly, cell-derived and individual ECM proteins increased
      tyrosinase activity in normal cutaneous melanocytes and effects of these ECM
      proteins were seen most consistently in mitogen-deficient media. Uveal
      melanocytes (as has been reported for cutaneous melanocytes) showed preferential
      attachment to fibronectin over other ECM substrates. This attachment was
      particularly sensitive to drugs which affected intracellular calcium or
      calmodulin activity. Acute addition of fibronectin to coverslips of uveal
      melanocytes loaded with Fura-2 produced an acute and transient increase in
      intracellular calcium which was more prevalent in low density than higher density
      cells. We conclude that ECM proteins in vitro are capable of influencing
      melanocyte morphology, tyrosinase activity, and proliferation and that an ECM
      induced elevation in intracellular calcium may be part of the signalling system
      that transmits ECM information into the cell.

PMID- 9170165
TI  - Sequence analysis of the human tyrosinase promoter from a patient with tyrosinase
      negative oculocutaneous albinism.
AB  - We examined the tyrosinase gene from a patient with tyrosinase-negative
      oculocutaneous albinism (OCA). First we studied the protein coding region,
      exon/intron junctions, and the proximal promoter region (positions -300 to +1) of
      her tyrosinase gene by direct sequencing. Although the results showed that she
      was heterozygote for the R77Q mutation, we could find no other mutation. To find
      a second mutation and compare the sequence in the 5'-flanking region of her
      tyrosinase gene between two OCA alleles, we amplified a 2422-bp stretch
      (positions -2065 to +357, including R77Q mutation site) by PCR, and cloned it
      into a plasmid vector. As a result, we discovered a difference between two OCA
      alleles in the GA repeat region. Therefore, we expect that the polymorphism in
      the GA repeat region of the tyrosinase gene will be used as a flanking marker of
      the OCA allele.

PMID- 9170166
TI  - The effect of ultraviolet B induced adult T cell leukemia-derived
      factor/thioredoxin (ADF/TRX) on survival and growth of human melanocytes.
AB  - Ultraviolet B (UVB) radiation is known to induce reactive oxygen species (ROS) in
      the skin. The skin, however, counteracts ROS by both constitutional and newly
      produced antioxidants. One such antioxidant, adult T cell leukemia-derived factor
      (ADF), a human homologue of thioredoxin (TRX), was shown to be efficiently
      produced in and released from cultured normal human keratinocytes after UVB
      irradiation by Northern and Western blot analyses and enzyme-linked
      immunoabsorbent assay (ELISA). Recombinant ADF (rADF) did not rescue UVB-induced
      melanocyte death, either when added pre- or post-UV irradiation. However, further
      addition of neutralizing antibody caused cell death of both keratinocytes and
      melanocytes. rADF was shown to induce higher expression in melanocortin-1
      receptor (MC1-R) mRNA accompanied by increased binding activity using 125I
      labeled [Nle4, D-Phe7]-alpha-MSH in melanocytes, leading to the enhanced
      increment of DNA synthesis. Taken together, it was shown that released ADF from
      UVB-irradiated keratinocytes acts as a survival factor for both keratinocytes and
      melanocytes but does not rescue UV-induced melanocyte death. Further, it may work
      as one of the stimulatory factors for UVB-induced melanogenesis by upregulating
      MSH-R binding activity in combination with the enhanced DNA synthesis by alpha
      MSH.

PMID- 9170167
TI  - Living and working in the sun: a symposium held as part of the XVIth
      International Pigment Cell Conference.

PMID- 9170168
TI  - Application of the new stereological probes to the study of the melanosome in
      Cloudman S91 melanoma cells.
AB  - The relationship between melanosome size and number and melanin content has been
      investigated in Cloudman S91 melanoma cells growing in vitro using both "model
      based" and "design-based" stereological procedures. Cells were cultured for 4
      days, harvested at daily intervals, and resin-embedded for light and electron
      microscopy; one aliquot of each sample of cells was assayed to determine its
      melanin content. By comparing their volume-weighted mean nuclear volume and their
      number-weighted mean nuclear volume, we have found that the nuclei of Cloudman
      melanoma cells form a fairly homogeneous population. The volume fraction and
      absolute volume of premelanosomes (VVpm, cell and Vpm) and mature melanosomes
      (VVmm, cell and Vmm) were all found to decrease progressively throughout the
      period of culture as did the number of premelanosomes (Npm) and mature
      melanosomes (Nmm). Whilst the volume-weighted mean volume of individual stage I
      and stage II premelanosomes, (VVipm), remained fairly constant at about 10 nm3,
      the volume of individual stage III and IV mature melanosomes showed significant
      variation ranging between about 13 nm3 and 32 nm3. The melanin content of the
      cells decreased progressively over the 4 days of culture. There were, however,
      considerable variations in both the average melanin content per unit volume of
      mature melanosomes, in the range 170-600 fg/micron3, and in the melanin content
      per individual mature melanosome, in the range 3-12 fg. Our findings show that
      stereological techniques can provide unbiased and sensitive tools for the study
      of the morphological basis of melanogenesis; their value will become even more
      evident when they are combined with techniques for the localization of
      melanogenic enzymes and their substrates.

PMID- 9170169
TI  - Melanocytes in vitro: how do they undergo mitosis?
AB  - Human melanocytes of the adult skin are slow-cycling cells with a highly
      dendritic morphology. Nevertheless in vitro proliferation can be achieved using
      adequate stimulators. Time lapse studies revealed the morphologic changes during
      melanocyte mitosis: dendrites are drawn back into the cell body, the cell becomes
      spherical and detaches from the support. Cell division takes place while the cell
      is suspended. Consecutively the two cells reattach to the support and form new
      dendrites. About 1% cells per culture are detached from the support and ca. 70%
      of these cells are viable and putative within mitosis. By every medium change
      mitotic cells become withdrawn supporting selection of G0-cells, Therefore we
      recommend centrifugation of exhausted medium in order to add mitotic cells back
      to the culture.

PMID- 9170170
TI  - Developing a consensus on quality criteria.

PMID- 9170171
TI  - Biologically based validation of PC electrophysiology data collection systems
      utilizing the Good Automated Laboratory Practices.
AB  - Since there was a scientific need to conduct electrophysiology measurements to
      detect possible ocular (electroretinography, ERG), central neurotoxic
      (quantitative electroencephalography, qEEG), and cardiac (electrocardiography,
      ECG) effects in animals used in certain regulatory studies, the acquisition of
      suitable automated PC software systems were required. This article describes the
      process by which these systems were validated to ensure that they met the
      scientific requirements, while also addressing the principles of Good Automated
      Laboratory Practices (GALP). After a thorough search of existing commercial
      packages, a plan was developed specific for each PC-based collection system
      selected for evaluation. The common elements of each plan included consideration
      of both scientific and GALP elements, such as necessary biological response
      variables, raw data acquisition and identification, acceptance criteria,
      security, protection, storage media, data integrity, audit requirements and
      standard operating procedures. The authors' approach to validation for each
      electrophysiology system was to determine scientific needs for accuracy,
      precision, and detection limit of biological effects concurrent with GALP
      requirements. The selected software systems were employed in separate scientific
      GLP studies conducted in dogs, rats, and mini-pigs to demonstrate the ability to
      detect cholinesterase effects due to multiple infusions of physostigmine, based
      on parallel measurement of cholinesterase biomarkers. Since the systems were
      designed for human usage, certain adaptations were necessary. A critical
      assumption to be tested was the ability of the system's algorithms to adequately
      capture and assimilate the data in an accurate fashion. Concomitantly, the
      related GALP needs, such as data integrity, security, CD-ROM archive, and
      personnel training requirements were evaluated, implemented, and defined to
      accommodate the application and process needs. The biological approach to
      validation of these PC-based electrophysiology systems met the necessary
      scientific acceptance criteria as well as compliance requirements in order to be
      used in regulatory studies.

PMID- 9170172
TI  - Toxicological considerations in environmental audit studies.
AB  - Environmental auditing has emerged as a new industrial management tool in recent
      years. It involves a careful examination of the organization, management
      procedures, product development, and equipment for environmental protection. The
      purpose of an environmental audit, from the toxicological point of view, is to
      assure that the total risk to humans, material, and environment should not
      increase as a result of a chemical process. The criteria to be adopted for such a
      safety audit are outlined.

PMID- 9170173
TI  - Integrating quality, safety, and environment management systems.
AB  - Internationally consistent ISO standards are in use, or are being developed, for
      quality systems, environmental management, and occupational health and safety.
      These standards outline a model for the management of quality, environment or
      safety. In many respects the process of developing management systems for these
      matters contains a number of common elements, including obtaining commitment from
      senior management; instituting consultative mechanisms; developing a policy;
      identifying components of the management program; resourcing, implementing, and
      reviewing the program; and integrating the program into the organization's
      strategic plan. The necessity of developing separate management systems for
      different organizational aspects is wasteful and inefficient. Better management
      systems will be developed if they are integrated into a single management
      structure.

PMID- 9170174
TI  - GLP soil characterization--the laboratory.
AB  - Good laboratory practices (GLP) for field studies have been implemented to
      provide accurate and complete data in all phases of field trials, including the
      characterization of the soil where the test system is grown. The soil
      characterization analysis generally offers two packages or series of analyses
      from which the sponsor may select. The Series I soil characterization is more
      comprehensive than the Series II. The Series II characterization includes pH,
      percent organic matter, cation exchange capacity (CEC), bulk density, percent
      sand-silt-clay, U.S. Department of Agriculture textural class, and 1/3-bar water
      holding capacity. In addition to these analyses, the Series I characterization
      includes: 15-bar water-holding capacity, and percent total nitrogen, phosphorus,
      and soluble salts.

PMID- 9170175
TI  - Quality assurance of clinical studies with production drugs.

PMID- 9170177
TI  - A historical progression of the Midwest Regional Chapter of the SQA.
AB  - The Historical Committee of the Midwest Regional Chapter of the Society of
      Quality Assurance has recorded and tracked the evolution and historical
      progression of our chapter from the initial authorization of regional chapters by
      the national society in 1990, through its growth in membership and area served,
      to its current status in October 1996. This article describes this growth as well
      as meeting attendance, location and topics of the training seminars, membership
      distribution, and the significant milestones accomplished as the chapter
      journeyed through a whirlwind past.

PMID- 9170176
TI  - A procedure for assessing a contract testing facility: one sponsor's perspective.
AB  - The government agencies responsible for Good Laboratory Practices (GLP) place
      accountability for assuring compliance of studies intended for submission on the
      sponsor. An initial step toward meeting these legal obligations includes a
      comprehensive assessment of the candidate testing facility. Literature review has
      substantiated that the initial evaluation may be best accomplished through both
      technical and compliance-focused inspections (O'Brien-Pomerleau, 1991; Schroeder,
      1989). Combined technical and compliance inspections have also been reported as
      an effective auditing approach for long-term studies (Hoover and Baldwin, 1984).
      However, for the purposes of the initial qualifying assessment inspection,
      personal experiences and published literature indicate that these two equally
      important evaluations are commonly conducted independently of one another
      (Scozzie, 1995). A collaborative approach utilized by Dow Corning Corporation in
      the preliminary assessment of a contract testing facility builds upon those
      methods just mentioned. Coupling this evaluation with a program of actively
      monitoring the testing facility's performance in study conduct provides continued
      assessment and has proven to be beneficial to all stakeholders (sponsor, testing
      facility, and regulatory agency). Details of the process practiced by this
      sponsor to assure that studies conducted by a contract testing facility meet GLP
      requirements are presented.

PMID- 9170178
TI  - Choose CE that's useful on the job today.

PMID- 9170179
TI  - Emphasize patient issues, not just professional issues.

PMID- 9170180
TI  - Drug administration practices in medical imaging: a survey.
AB  - Radiology administrators nationwide were surveyed to determine current drug
      administration practices in their imaging departments. The survey also obtained
      information about the educational backgrounds of radiologic technologists
      administering pharmaceuticals and the documentation procedures used by imaging
      departments. Survey results showed that 86% of responding institutions allow
      radiologic technologists to administer pharmaceuticals. However, the amount and
      type of education technologists received regarding drug administration was
      limited. In addition, the type of legal documentation regarding the
      administration of contrast media varied considerably among the responding
      institutions.

PMID- 9170181
TI  - Survey of contrast media use in southeastern U.S. hospitals.
AB  - This article reports the results of a survey of contrast media usage in hospitals
      in five southeastern states. Forty-three percent of hospitals surveyed reported
      using nonionic contrast media 100% of the time, while 71% used nonionic contrast
      more than 75% of the time. Hospitals with fewer than 399 beds showed an increase
      in universal nonionic contrast usage compared to hospitals with more than 400
      beds. Survey results also showed that radiographers administer contrast media in
      90% of hospitals. On average, radiographers administered contrast twice as often
      as radiologists. Hospitals favored selective protocols as the primary method to
      reduce nonionic contrast media usage. The low rate of reactions for nonionic
      contrast was the primary reason hospitals chose to use nonionic contrast.

PMID- 9170182
TI  - Radiographic evaluation of the soap man mummy.
AB  - This article describes how mobile radiography was used to examine a mummified
      cadaver exhumed in 1875 and stored in the Smithsonian Museum. Radiographs
      revealed artifacts imbedded in the cadaver, indicating 1824 as the earliest
      possible interment. Through radiographic assessment of the skeleton, researchers
      were able to approximate the individual's age at death. In addition, evidence of
      pathology, possibly ideopathic skeletal hyperostosis, suggested the individual
      may have been employed in manual labor. The radiographs, when compared to x-rays
      of another cadaver exhumed at the same time and place, refuted information in
      museum records.

PMID- 9170183
TI  - Defecation disorders and the role of defecography.
AB  - This continuing education article discusses abnormalities of defecation and the
      physical mechanisms by which these abnormalities occur. The article also
      describes the role of defecography and other imaging techniques used to diagnose
      abnormalities of defecation.

PMID- 9170184
TI  - A matter of degrees.

PMID- 9170186
TI  - The double outline sign.

PMID- 9170185
TI  - CA and leukemia group B 9251 protocol.

PMID- 9170187
TI  - Patient rapport in radiologic technology.

PMID- 9170188
TI  - Film viewing conditions in mammography.

PMID- 9170189
TI  - A guide for technical query contributors.

PMID- 9170190
TI  - Teaching critical thinking skills.

PMID- 9170191
TI  - Interactive questioning: why ask why?

PMID- 9170192
TI  - Add managed care to clinical education.

PMID- 9170193
TI  - CT improves diagnosis of pneumonia.

PMID- 9170194
TI  - Expand technology by sharing ideas.

PMID- 9170195
TI  - Magnet programs for student recruitment.

PMID- 9170196
TI  - Ductular expression of autoantigens in primary biliary cirrhosis.
AB  - The role of biliary epithelial cell (BEC) antigens in immune recognition and
      damage of biliary epithelium in primary biliary cirrhosis (PBC) is unknown. The
      major autoantigen in PBC (the mitochondrial enzyme pyruvate dehydrogenase
      dihydrolipoamide acetyltransferase [PDC-E2]) is abnormally distributed in the
      biliary epithelium of patients with PBC relative to controls. The antigen is not
      only present in mitochondria but also associated with the BEC plasma membrane.
      This atypical distribution of PDC-E2 is present both in early (stages I-II) and
      advanced (stages III-IV) disease, suggesting a role for the antigen in
      progression and/or etiology of PBC. The identity of the plasma membrane antigen
      remains unknown, but there is evidence to suggest that it is an antigen that
      cross reacts with antibodies to PDC-E2. Use of BEC purified from human liver may
      help in deciphering the possible importance of BEC plasma membrane antigens in
      immune recognition and toxicity toward BEC in PBC.

PMID- 9170197
TI  - The role of T cells in primary biliary cirrhosis.
AB  - While fervently studied by several laboratories, the role of T cells in the
      pathogenesis of primary biliary cirrhosis (PBC) still remains a mystery. The
      studies concerning cell phenotype, antigen specificity, and major
      histocompatibility complex (MHC)-T-cell receptor (TCR) interaction gathered thus
      far all address important aspects of this intriguing conundrum. However, the lack
      of an animal model and the genetic diversity of the human population with PBC
      make this task even more difficult. The possibilities regarding immune therapy
      resulting from such studies are of great importance. Future work concerning the T
      cell epitopes--for both the pyruvate dehydrogenase complex (PDC), its related
      mitochondrial autoantigens, and any as yet unidentified PBC-specific autoantigens
      -may provide valuable information with regard to disease therapy. In addition,
      knowledge with regard to TCR usage and MHC association will help to clarify the
      pathogenic mechanisms of this enigmatic disease.

PMID- 9170198
TI  - Cytokines in primary biliary cirrhosis.
AB  - Immunoreactivity to intra- and extracellular antigens is regulated mainly by two
      different types of T-helper cells, namely TH1 (producing mainly IFN-gamma and Il
      2) and TH2 (producing IL-4, -5, -10). Both types cross-regulate each other. TH1
      mechanisms seem to be involved principally in organ-specific autoaggressive
      disorders, while TH2 response is an expression of allergic conditions
      characterized by eosinophilic reactions and increased IgE levels. There are only
      a few reports dealing with cytokine profiles in patients with primary biliary
      cirrhosis (PBC). From studies analyzing the cytokine gene expression and
      cytokines in supernatants of nonstimulated and antigen-specific lymphocytes
      derived from the affected liver or peripheral blood of PBC patients, there is
      evidence that, in the course of the disease, predominantly TH1 cells are
      activated. However, in view of the eosinophilic reaction observed especially in
      patients with early PBC, it may well be that a switch from TH2 to TH1 occurs.
      Concerning the regulatory function of TH1/TH2 cells, a more refined evaluation of
      these T-cell subsets could help to provide a new insight into the natural course
      of PBC.

PMID- 9170199
TI  - Ursodeoxycholic acid in primary biliary cirrhosis.
AB  - In patients with primary biliary cirrhosis (PBC), ursodeoxycholic acid (ursodiol)
      improves laboratory test markers of cholestasis and hepatic inflammation as well
      as some hepatic histological features; it also delays histological progression in
      the early stages of PBC. Ursodiol is well tolerated and safe. Less well
      substantiated are that ursodiol either improves the quality of life or prevents
      liver transplantation or that it prolongs survival without transplantation. There
      are favorable trends for ursodiol in preventing transplantation and prolonging
      survival, but in the absence of randomized, placebo-controlled trials of
      sufficient duration, there remain impressions rather than statistically proved,
      strong conclusions.

PMID- 9170200
TI  - The use of methotrexate, colchicine, and other immunomodulatory drugs in the
      treatment of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which
      activated T lymphocytes attack and destroy epithelial cells in the small
      intralobular bile ducts of genetically susceptible patients. This article reviews
      the results of treatment of PBC with immunomodulatory agents. Results with drugs
      such as glucocorticoids, azathioprine, and chlorambucil have been disappointing
      because of either limited efficacy (azathioprine), toxicity (chlorambucil), or
      both (glucocorticoids). Colchicine improved tests of liver function in three
      prospective studies and was associated with improved survival for up to 4 years.
      However, survival benefits were lost at 8 years. Colchicine appears to slow the
      rate of progression of PBC but not to stop it. Preliminary results suggest that
      colchicine may have synergistic effects if used together with ursodeoxycholic
      acid, particularly in patients who are only partially responsive to
      ursodeoxycholic acid. Results with cyclosporine have been disappointing because
      of limited efficacy and predictable toxicity. The modest improvement in tests of
      liver function and survival are counterbalanced by the development of
      hypertension in some and worsening renal function in most. There is little
      beneficial effect on symptoms or histology. Results with methotrexate are
      promising. There are improvements in symptoms and tests of liver function that
      are equal to those seen with ursodeoxycholic acid and significant improvement in
      liver histology. Some patients, particularly those with striking inflammation and
      granulomas in portal triads, appear to have achieved sustained remission while on
      methotrexate. The effects of methotrexate are additive to those of
      ursodeoxycholic acid in patients whose blood tests have responded only partially
      to ursodeoxycholic acid. The most effective treatment of PBC will most likely use
      a combination of drugs such as ursodeoxycholic acid, colchicine, and
      methotrexate.

PMID- 9170201
TI  - Transplantation for primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) remains one of the commoner indications for
      orthotopic liver replacement. The two main indications for transplantation are
      poor quality of life (because of the liver) or end-stage liver disease. A number
      of prognostic models have identified risk factors indicating poor prognosis, but
      in practice serum bilirubin greater than 150 mumol/L is used most commonly. Other
      indications for transplantation include progression of hepatopulmonary syndrome,
      increasing osteoporosis, evidence of malnutrition, and development of
      hepatocellular carcinoma. Postoperatively, patients do well. Recurrence of PBC
      remains controversial, but an increasing number of centers now report that a
      proportion of patients develop evidence of recurrent disease in the allograft. As
      yet PBC recurrence remains of little practical importance, although as survival
      increases beyond 10 years, this may become more relevant.

PMID- 9170203
TI  - Job patterns of disabled beneficiaries.
AB  - This article presents basic findings about the job patterns of disabled-worker
      beneficiaries covered under the Social Security Administration Disability
      Insurance (DI) program as reported in the New Beneficiary Follow-up survey.
      Beneficiaries are asked retrospective questions about labor-force participation
      from the time of their first entitlement to disability benefits to the time of
      the interview. Twelve percent of those persons who enter the DI program as
      nonworking beneficiaries start a job during their entitlement to benefits. The
      mean time to the start of the job was 3.4 years. Of those who start a job, 50
      percent end the job before the end of their entitlement. Most of these persons
      leave the job for health-related reasons and, for most of them, the employer does
      not play a major role in their decision to stop working. For those who end the
      first job and are employed in subsequent jobs, the percentage who recover while
      still in the job decreases as the number of jobs increases.

PMID- 9170202
TI  - Survival algorithms and outcome analysis in primary biliary cirrhosis.
AB  - The natural history of primary biliary cirrhosis (PBC) is one of slowly
      progressive cholestasis with liver damage, development of cirrhosis with its
      concomitant complications, and death unless the patient undergoes liver
      transplantation. Natural history studies have identified several variables
      associated with a decreased survival in patients with PBC. The course of the
      disease can be divided into three time periods: (1) a presymptomatic phase,
      probably lasting up to 20 years; (2) a symptomatic phase, with anicteric or mild
      jaundice, lasting up to 5 to 10 years; and (3) a preterminal or accelerated phase
      with marked jaundice, lasting up to 2 years. Since the course of the disease is
      one of slow progression leading to liver failure and death unless liver
      transplantation intervenes, several investigators have developed statistical
      models to predict survival. The ability to predict survival for individual
      patients with PBC has been valuable in the management of these patients,
      particularly in patient selection and timing of liver transplantation. In
      addition, survival estimates can be utilized in education and counseling patients
      and their families. These models may also be used to evaluate the efficacy of new
      treatments by comparing natural history survival with the survival achieved by
      therapeutic effect. Over the past several decades, the natural history models of
      PBC have been developed in the absence of effective medical therapy. The efficacy
      of liver transplantation and survival following liver transplantation has now
      been quantitatively established. Future efforts should be aimed at determining
      not only survival of patients with primary biliary cirrhosis in the presence of
      effective medical therapy but also at assessing the quality of life and cost
      effectiveness of medical therapy and liver transplantation in the management of
      patients with primary PBC.

PMID- 9170204
TI  - Family unit incomes of the elderly and children, 1994.
AB  - The economic status of the elderly and that of children are analyzed using a
      comprehensive definition of income that takes selected types of noncash income
      and taxes into account. Estimates are presented for detailed age groups over the
      entire age range and for socioeconomic classifications within the elderly
      subgroup and within the subgroup of children. The article finds that children and
      the elderly are less well-off than the middle age groups. This result is obtained
      using median incomes and the percentage of the group that has low income, as
      defined in this article. When results obtained with the measures presented in
      this article are compared with those obtained with more commonly used measures,
      there are important differences for both the elderly and for children. For both
      groups, the composition of the low-income population differs in important ways
      from the composition of the official poverty population.

PMID- 9170205
TI  - The economics of retirement: a nontechnical guide.
AB  - Concern about the economic consequences of the aging of the United States
      population has prompted considerable research activity during the past two
      decades. Economists have carefully examined retirement patterns and trends, and
      sought to identify and measure the determinants of the timing of retirement by
      older workers. Much of the published retirement research is fairly technical by
      nature and is somewhat inaccessible to nonspecialist audiences. This article
      provides a nontechnical overview of this research. In contrast to other reviews
      of the retirement literature, this exposition emphasizes the basic ideas and
      reasoning that economists use in their research. In the course of recounting how
      economists' views about retirement have evolved in recent years, the article
      highlights landmark pieces of research, point out the specific advances made by
      the various researchers, and assesses what has been learned along the way.

PMID- 9170206
TI  - Excerpt from the report of the 1994-96 Advisory Council on Social Security:
      findings and recommendations.

PMID- 9170207
TI  - Research Grant Summary.
AB  - Several factors must be evaluated to determine the savings to the Social Security
      Trust Fund of increasing the normal retirement age above 65. What was examined
      was the cost savings that could be attributed to raising the normal retirement
      age from 6 to 120 months above age 65 after adjusting for possible increases in
      disability incidence with age and for the higher mortality of disabled persons
      between ages 65 and 75. Other sets of potentially significant factors, not
      explicitly examined above, are labor-market conditions (that is, how many and
      what types of jobs are available for older workers), and psychological factor
      (that is, the motivation to continue gainful employment). The calculations show
      that, other things being equal, increases in disability prevalence between ages
      65 and 75 will not substantially reduce the cost savings attributable to
      increasing the normal retirement age up to age 75. Thus, assuming that the U.S.
      labor market can absorb large numbers of older workers, and that older workers
      will be motivated to continue working, the savings generated by increases in
      normal retirement ages could be quite large. Indeed, with an increase of the
      normal retirement age of 70 or 72, it might be possible to provide much of the
      cost savings needed to meet the increased demands that will be put on the Social
      Security Trust Fund when the greatest number of the World War II baby boom
      cohorts reach age 65 in 32 years, in 2028. This savings may be possible because,
      in addition to the cost savings to the SSA pension program, the proportion of the
      population that continues to work until age 70 (or 72) will also contribute to
      the payroll tax. Their actual contribution will depend upon the numbers of older
      workers and their average wage rates. Nonetheless, the savings in pension costs
      (even adjusting for potential increases in disability with age), and the
      potential increases in payroll tax revenues, should significantly contribute to
      bringing the trust funds into actuarial balance.

PMID- 9170208
TI  - Retroviral stem cell gene therapy.
AB  - Long-term in vivo gene transfer studies in mice have shown that recombinant
      murine retroviruses are able to infect murine hemopoietic stem cells with high
      efficiency. Taken together the results indicated that the proviral structure was
      present at high frequency in circulating hemopoietic cells resulting in
      significant expression levels. Because of the success of these murine studies, it
      was believed that gene therapy would soon be applicable to treat a wide variety
      of congenital or acquired human diseases associated with the hemopoietic system.
      However, results from gene transfer studies in nonhuman primates and first human
      clinical trails have indicated that murine retrovirus infection of primate
      hemopoietic stem cells is inefficient. Although there are essential differences
      between the murine and primate gene therapy studies with respect to the
      recombinant viruses and transduction protocols used, these differences cannot
      solely account for the differences observed in infection efficiency. Therefore,
      in recent years effort has been spent on the identification of factors limiting
      retroviral transduction of primate hemopoietic stem cells. Increasing knowledge
      concerning hemopoiesis and retroviral infection has helped in identifying a
      number of limiting factors. Novel transduction strategies and tools have been
      generated which attempt to circumvent these limiting factors. These factors as
      well as the strategies that showed increased retroviral infection of primate
      hemopoietic stem cells will be discussed.

PMID- 9170209
TI  - The regulation of neovascularization of matrix metalloproteinases and their
      inhibitors.
AB  - The process of new capillary formation from preexisting vessels, angiogenesis, is
      a complex physiological event which is strictly controlled, occurring only very
      rarely under normal conditions. In contrast, there are a number of serious
      diseases, among them solid tumor growth, rheumatoid arthritis and several eye
      diseases, which are characterized by unrestricted new capillary growth and which
      are described as "angiogenic diseases." One of the key events required for
      successful angiogenesis is extracellular proteolysis. Increased attention has
      been focused on matrix metalloproteinase (MMP) family of enzymes whose activity
      is a rate-limiting step in extracellular matrix remodeling. This review will
      present the accumulating body of evidence, from a number of laboratories, which
      documents the important role of MMP activity in the regulation of angiogenesis.
      Taken together, these data suggest that one strategy for controlling the
      deregulated angiogenesis characteristic of these serious angiogenic diseases may
      be one which is operative at the level of the control of MMP activity.

PMID- 9170210
TI  - TGF-beta latency: biological significance and mechanisms of activation.
AB  - Transforming growth factor (TGF-) beta is secreted as a latent complex in which
      the mature growth factor remains associated with its propeptide. In order to
      elicit a biological response, the cytokine must be released from the latent
      complex, a process termed latent TGF-beta activation or TGF-beta formation.
      Although latent TGF-beta activation is a critical step in the regulation of its
      activity, little is known about the molecular mechanisms that lead to the
      production of active TGF-beta. In this article, we present an overview of the
      data available on this topic, and we propose a tentative model for the mechanism
      of TGF-beta formation based upon the observations with different cell systems and
      on recent findings on the structure of the latent TGF-beta complex.

PMID- 9170211
TI  - Evaluation of cytokines for expansion of the megakaryocyte and granulocyte
      lineages.
AB  - The goal of our study was to identify cytokine combinations that would result in
      simultaneous ex vivo expansion of both the megakaryocyte (Mk) and granulocyte
      lineages, since these cell types have the potential to reduce the periods of
      thrombocytopenia and neutropenia following chemotherapy. We investigated the
      effects of cytokine combinations on expansion of the Mk (CD41a+ cells and colony
      forming unit [CFU]-Mk) and granulocyte (CD15+ cells and CFU-granulocyte/monocyte
      [GM]) lineages. Peripheral blood CD34+ cells were cultured in serum-free medium
      with interleukin 3 (IL-3), stem cell factor (SCF), and various combinations of
      thrombopoietin (TPO), IL-6, GM-CSF, and/or G-CSF. The Mk lineage was primarily
      influenced by TPO in our cultures, although Mk and CFU-Mk numbers were increased
      when TPO was combined with IL-6. The primary stimulator of the granulocyte
      lineage was G-CSF, although many synergistic and additive effects were observed
      with addition of other factors. Expansion of CFU-GM increased upon addition of
      more cytokines. The cytokine combination of IL-3, SCF, TPO, IL-6, GM-CSF and G
      CSF produced the greatest number of granulocytes and CFU-GM. The minimum
      cytokines necessary for expansion of both the Mk and granulocyte lineages
      included TPO and G-CSF, since no other factors examined could increase Mk and
      granulocyte numbers to the same extent. The number of hematopoietic progenitors
      produced in our culture system should be sufficient for successful engraftment
      following myelosuppressive therapy if produced on a scale of about one liter.

PMID- 9170212
TI  - In vitro growth of mobilized peripheral blood progenitor cells is significantly
      enhanced by stem cell factor.
AB  - The existence of primitive hematopoietic progenitors in mobilized peripheral
      blood is suggested by clinical, phenotypic and in vitro cell culture evidences.
      In order to quantify primitive progenitors, 32 leukaphereses from 15 patients
      with lymphoid malignancies were investigated for the growth of multilineage
      colony-forming units (CFU-Mix), erythroid burst-forming units (BFU-E) and
      granulocyte-macrophage colony-forming units (CFU-GM) in the absence or presence
      of recombinant stem cell factor (SCF), a cytokine which selectively controls stem
      cell self-renewal, proliferation and differentiation. Primitive progenitors were
      also quantitated by means of a long-term assay which allows the growth of cells
      capable of initiating and sustaining hematopoiesis in long-term culture (LTC-IC).
      Addition of SCF (50 ng/ml) to methyl-cellulose cultures stimulated with maximal
      concentrations of G-CSF, GM-CSF, interleukin 3 and erythropoietin significantly
      increased the growth (mean +/- SE) of CFU-Mix (7.7 +/- 1.7 versus 2.4 +/- 0.6, p
      < or = 0.0001), BFU-E (47 +/- 10 versus 32 +/- 6, p < or = 0.002) and CFU-GM (173
      +/- 31 versus 112 +/- 20, p < or = 0.0001). Mean (+/- SE) percentages of SCF
      dependent CFU-Mix, BFU-E and CFU-GM were 60 +/- 5%, 19 +/- 5%, and 33 +/- 4%,
      respectively. Mean (+/- SE) LTC-IC growth per 2 x 10(6) nucleated cells was 221
      +/- 53 (range, 2 to 704). Linear regression analysis demonstrated a statistically
      significant correlation (r = .87; p < or = 0.0001) between LTC-IC and SCF
      dependent progenitors. In conclusion, our data suggest that: A) the optimal
      quantification of mobilized progenitors requires supplementation of
      methylcellulose cultures with SCF, and B) in vitro detection of SCF-dependent
      progenitors might represent a reliable and technically simple method to assess
      the primitive progenitor cell content of blood cell autografts. Such in vitro
      evaluation of immature hematopoietic progenitors might be clinically relevant for
      predicting the reconstituting potential of autografts.

PMID- 9170213
TI  - Optimization of the cycling of clonogenic and primitive cord blood progenitors by
      various growth factors.
AB  - The cycling status of cord blood progenitors and the culture conditions
      triggering their activation into S-phase have been studied using flow cytometry
      and a 3H-thymidine suicide assay. Mononuclear cells cultured either in Iscove's
      modified Dulbecco's medium (IMDM) +/- 10% fetal calf serum ([FCS]; IMDM + FCS) or
      in Dulbecco's modified Eagle's medium (DMEM) +/- 10% newborn bovine serum ([NBS];
      DMEM + NBS) were stimulated by various growth factors (GFs). Results showed that
      CD34+ cells, clonogenic progenitors (colony forming cells [CFCs]) and long-term
      culture initiating cells (LTC-IC) present in freshly harvested cord blood were
      quiescent. CFC numbers were maintained without cycling after 48-h cultures in
      serum-containing media without GFs. Addition of interleukin 3 (IL-3) + IL-6 +
      stem cell factor stimulated into S-phase approximately 40% of CFCs within 24-48
      h, without modifying their number except in DMEM + NBS where erythroid
      progenitors decreased. When cells were stimulated in IMDM + FCS by these three
      GFs + insulin-like growth factor I and basic fibroblast growth factor used at
      high concentration, more than 50% of CFCs were in S-phase and their total number
      was maintained. The latter culture conditions also recruited up to 66% of LTC-IC
      into S-phase. Our data underline the importance of the combination of GFs and
      culture media used for optimizing the cycling and maintenance of CFCs and LTC-IC
      within two days.

PMID- 9170215
TI  - Adhesion of thymocytes to bone marrow stromal cells: regulation by bFGF and IFN
      gamma.
AB  - We recently reported on selective interactions between immature T cell
      subpopulations and bone marrow (BM) stromal cells. To further study this process,
      we first examined the efficacy of methods estimating cell-cell adhesion and then
      investigating the effects of cytokines on thymocyte-stroma associations.
      Techniques based on the use of the fluorochromes calcein-acetomethylester
      (calcein-AM) and fluorescein diacetate (FDA) were studied and compared to regular
      cell counting methods. With calcein-AM labeling, the retention time was
      relatively long, while with FDA labeling, there was a rapid cellular efflux.
      Using calcein-AM, we developed an accurate quantitative fluorometric assay for
      determining the adherence of thymocytes to a BM stromal cell line (MBA-13). A
      maximal fraction of about 29% thymocytes was found to adhere to confluent MBA-13
      cell layers after four to six h of coculture. Whereas interleukin 1 did not
      change the rate of adhesion of thymocytes to the stroma, interferon-gamma (IFN
      gamma) significantly increased adhesion. Basic fibroblast growth factor (bFGF)
      had a dose-dependent biphasic effect on thymocyte adhesion, and a greater
      fraction of double negative thymocytes adhered to stroma pretreated with bFGF.
      Taken together, these results suggest that IFN-gamma and bFGF modulate T cells-BM
      stromal cell adhesion.

PMID- 9170214
TI  - Decreased or altered expression of the FHIT gene in human leukemias.
AB  - The FHIT (fragile histidine triad) gene on chromosome 3p14 is a candidate tumor
      suppressor gene, and its transcripts are shown to be abnormal in several human
      cancers. We examined 40 leukemia samples for the alterations of FHIT transcripts
      by reverse transcriptase-polymerase chain reaction (RT-PCR) and direct
      sequencing. Intact FHIT mRNA was not detected in two patients with acute myeloid
      leukemia (AML) and in one patient with chronic lymphocytic leukemia (CLL). The
      three cases expressed only an aberrant FHIT mRNA lacking exons 3 to 6 (FHIT delta
      3-6 mRNA), which could encode a polypeptide of 13 amino acids. Southern blot
      analysis on two samples from these cases showed no rearrangements of the FHIT
      gene. Although intact FHIT mRNA was detected as the main band in the remaining 37
      samples, 33 of them (14 of 14 AML, 11 of 13 chronic myeloid leukemia, five of
      five acute lymphocytic leukemia, and three of five CLL) expressed aberrant FHIT
      delta 3-6 mRNA. We barely detected the FHIT delta 3-6 mRNA in only one of 25
      normal control samples. Our results suggest that loss of the normal FHIT function
      may be involved in the genesis of at least some human leukemias and that
      expression of aberrant FHIT transcripts is rather specific and frequent in
      leukemia samples.

PMID- 9170216
TI  - Serum-free culture conditions for cells capable of producing long-term survival
      in lethally irradiated mice.
AB  - The goal of ex vivo culture is to expand and/or differentiate cells in culture
      such that they retain their functional characteristics when reinfused into a
      patient. The studies presented here analyzed the use of culture conditions devoid
      of serum to expand murine hematopoietic stem cells. Bone marrow cells from male
      B6D2F1/J mice were cultured for up to 28 days in serum-free medium in the absence
      or presence of stem cell factor (SCF), GM-CSF or a combination of the two
      factors. Cells cultured for up to 21 days were assessed for granulocyte
      macrophage colony-forming cells (GM-CFC), spleen colony-forming units, and cells
      responsible for short-term and long-term hematopoietic repopulation in lethally
      irradiated mice. Compared to initial seeding levels, the presence of SCF and GM
      CSF increased total cell numbers 90-fold and GM-CFC numbers 42-fold over a 21-28
      day culture period. Although spleen colony-forming unit cells did not increase,
      they were maintained at initial seeding levels over a 21-day period in the
      presence of SCF and GM-CSF. In lethally irradiated mice, survival enhancement and
      hematologic reconstitution were optimum with cells cultured for only seven days:
      survival at six months was 100% with cells cultured in SCF plus GM-CSF or SCF
      alone, compared to 50% with cells cultured with only GM-CSF. Hybridization
      analysis of bone marrow, spleen and thymus DNA from irradiated mice transplanted
      with these cultured cells confirmed male donor cell-derived repopulation at 45
      days and 180 days post-transplant. These studies illustrate that murine GM-CFC
      can be expanded and that long-term repopulating hematopoietic cells can, at the
      minimum, be maintained ex vivo in serum-free culture. The use of defined serum
      free culture systems holds great promise for further evaluation of the mechanisms
      that control hematopoietic stem cell proliferation.

PMID- 9170217
TI  - Bilateral bone anchor vaginal vault suspension: an initial report of a new
      technique.
AB  - Vaginal vault prolapse is usually treated by sacrospinous fixation. Although this
      procedure is very effective, it is associated with various complications that
      include injury to the pudendal neurovascular structures, the sciatic nerve,
      and/or chronic gluteal pain. A safer and simpler modification of sacrospinous
      vaginal vault suspension using the Vesica bone anchor kit is reported. Vaginal
      vault prolapse was corrected in six patients by suspending the apex of the
      vaginal vault to the ischial spine with Vesica bone anchors. Bladder neck
      suspension and correction of other vault pathology was performed at the same
      time. All patients had complete relief of their prolapse and have demonstrated no
      recurrence during the brief mean follow-up period of 7 months.

PMID- 9170219
TI  - Noninsufflative extraperitoneal laparoscopic varicocele ligation.
AB  - Currently, most laparoscopic procedures are performed through the intraperitoneal
      route utilizing standard insufflative technique to create a working space. We
      report our experience with the new technique of gasless extraperitoneal
      varicocelectomy performed in eight subfertile men, in which we effectively
      dissect the retroperitoneum by using a trocar balloon device (peritoneal
      distention balloon) and maintain the working cavity with a motorized abdominal
      wall retractor (Laparofan/Laparolift retraction system). In addition to the
      primary trocar, two valveless secondary trocars are placed, through which either
      laparoscopic or standard surgical instruments may be used. The spermatic veins
      are doubly clipped while the artery is preserved in all cases. The mean operative
      time was 150 +/- 51 min with no intraoperative complications, and all patients
      were discharged within 24 h. The average days to return to work was 6.5 +/- 3.0
      and the average postoperative analgesic requirement (pain pills) was 23.5 +/-
      9.9. There were no significant postoperative complications. Exposure and working
      space provided by the gasless technique are not as satisfactory as the standard
      insufflative technique, and operative time is far more extensive. To surmount
      these limitations in gasless laparoscopy, significant developments are required
      in retraction technology.

PMID- 9170218
TI  - "Tubeless" percutaneous surgery: a new advance in the technique of percutaneous
      renal surgery.
AB  - We describe our modification of the technique of traditional percutaneous renal
      surgery called "tubeless" percutaneous renal surgery. Fifty patients have now
      undergone percutaneous renal procedures without the use of a postoperative
      nephrostomy tube consisting of percutaneous nephrolithotripsy, percutaneous
      endopyelotomy, and both percutaneous stone extraction and endopyelotomy in the
      same setting. Our current modification of standard percutaneous surgical
      technique includes the placement of an internal ureteral catheter with primary
      closure of the access site using hemostatic skin sutures. The study group was
      compared to a control group of 50 patients who were age, sex and procedure
      matched who had undergone standard percutaneous renal procedures previously with
      routine placement of postoperative nephrostomy tubes. The incidence of
      complications, analgesia requirements, length of hospitalization, time of return
      to normal activities, and cost of treatment were compared between the two groups.
      All tubeless percutaneous procedures were successfully performed without
      significant complications. The initial 15 patients had postoperative renal
      ultrasounds demonstrating no urinoma. Hospital stay, analgesia requirements, and
      the patient's ability to return to normal activities were statistically
      significantly decreased in the patient group studied. The cost of a "tubeless"
      procedure was $1,638 compared with $3,750 (129% greater) for traditional
      percutaneous surgery (cost saving of $2,112/case). Tubeless percutaneous renal
      surgery is a safe procedure and offers advantages over the routine placement of a
      nephrostomy tube. The hospitalization period, analgesia requirements, return to
      normal activities, and cost are significantly less with this new technique.

PMID- 9170220
TI  - Current treatment of advanced prostate cancer.
AB  - Metastatic prostate cancer has been traditionally treated with androgen ablation
      using surgical orchiectomy or estrogens. The development of long lasting LHRH
      analogues has replaced these standard treatments in most patients with advanced
      prostate cancer. Several nonsteroidal antiandrogens are now available that may be
      used in combination therapy with LHRH analogues. This approach has been
      demonstrated in several large trials to improve the control of the disease. In
      spite of these advances, most men will eventually develop hormone resistance. New
      strategies being investigated include intermittent androgen ablation and
      combining initial hormonal therapy with chemotherapeutic agents. The management
      of hormone refractory disease remains a major clinical problem, with few standard
      chemotherapy agents demonstrating activity. This article reviews the principles
      of the current management of advanced prostate cancer and introduces some of the
      newer strategies under investigation.

PMID- 9170221
TI  - Transurethral vaporization of the prostate in the treatment of bladder outlet
      obstruction at two university hospitals.
AB  - Transurethral vaporization of the prostate (TVAP) is a new technique for the
      surgical treatment of men with benign prostatic hyperplasia (BPH). The primary
      advantage of TVAP appears to be shortened hospitalization and less bleeding than
      is associated with transurethral resection of the prostate (TURP). Since February
      1995, 66 consecutive men with bladder outlet obstruction (47 with persistent
      voiding symptoms and 19 in complete urinary retention) secondary to prostatic
      disease underwent TVAP at two university hospitals. TVAP was utilized in all
      patients regardless of prostate size. The mean length of follow-up was 3.2
      months. All 19 men in complete retention were able to void adequately following
      surgery with a mean postvoid residual volume of 18cc and a mean International
      Prostate Symptom Score (I-PSS) of 7.5. In the remaining patients, the I-PSS
      decreased from a mean of 19.6 to 8.4. Pre- and postoperative peak urinary flow
      rate data were available in 17 men and increased from 9 to 18 cc/s. Limited
      transurethral resection of prostatic tissue at the completion of TVAP was
      necessary to adequately relieve bladder outlet obstruction in 18% (12/66) of
      patients. Hospitalization of < 24 h was needed in 68% (45/66) patients. The
      urinary catheter was removed within 1 day of surgery in 68% (45/66) of men as
      well. Seven patients required catheter replacement postoperatively due to
      difficulty voiding (five men) or bleeding (two men). No patient required blood
      transfusion. TVAP is effective in relieving bladder outlet obstruction in men
      with and without urinary retention. The majority of patients require brief or no
      hospitalization and are able to void adequately within 24 h of surgery. TVAP
      appears to be less effective in men with large prostate glands, and limited TURP
      is more frequently needed in these cases. The long-term results of TVAP will
      require further study.

PMID- 9170222
TI  - The utility of the Malone antegrade continence enema for urologists.
AB  - Urologists often manage patients with neurogenic voiding dysfunction. These
      patients often have neuropathic bowel dysfunction. The malone antegrade
      continence enema (ACE) performed synchronously with a urinary continence
      procedure has been successful in pediatric patients. We report preliminary
      experience combining the ACE with a urinary continence procedure in two adult
      neurogenic patients. The ACE procedure is technically easy. Both patients had a
      separate urinary stoma and an appendicocecostomy for their ACE. Both patients are
      continent of stool at their appendicocecostomy and per rectum. Both patients have
      stabilized their urinary tracts. Complications were minimal. The ACE may benefit
      adult patients with impaired bowel evacuation and may be combined with a urinary
      continence procedure. Urologists can easily perform the ACE.

PMID- 9170223
TI  - Laparoscopic access with a visualizing trocar.
AB  - Although useful in most situations, there are several inherent disadvantages of
      the standard laparoscopic access techniques of Veress needle insertion and Hasson
      type cannula placement. Veress needle placement may be hazardous in patients at
      high risk for intraabdominal adhesions and difficult in patients who are obese.
      The usual alternative, the Hasson-type cannula, often does not provide a good gas
      seal. As another option, the use of a visualizing trocar (OPTIVIEW) has proven to
      be effective in the initial experience at the University of Michigan. The inner
      trocar of the visualizing trocar is hollow except for a clear plastic conical tip
      with two external ridges. The trocar-cannula assembly is passed through tissue
      layers to enter the operative space under direct vision from a 10-mm zero-degree
      laparoscope placed into the trocar. Results suggest that this technique is an
      excellent alternative to Veress needle placement when laparoscopic access is
      likely to be hazardous or difficult.

PMID- 9170224
TI  - The Pre and Post Massage Test (PPMT): a simple screen for prostatitis.
AB  - The segmented quantitative culture technique originally described more than 25
      years ago is acknowledged as the best test to diagnose prostatitis. However, it,
      is not widely used in clinical practice. This is especially true in primary care
      settings, but even most urologists appear to have abandoned the procedure. Herein
      is proposed a simple and cost-effective screen for prostatitis, which involves
      the culture and microscopic examination of urine before and after prostatic
      massage. This Pre and Post Massage Test (PPMT) was applied to a personal series
      of 53 patients and 59 patients from the literature in whom the results of the
      segmented cultures are available and the results were reevaluated. In this
      selected patient population the PPMT alone led to the same diagnosis in 102
      (91.1%). Within the expected limitations of this retrospective review, the
      calculated sensitivity and specificity of the PPMT were both 91%. This report
      should provoke researchers to review their prostatitis data, stimulate
      discussion, and hopefully convince physicians that adoption of a simpler
      diagnostic plan for prostatitis is far superior to doing no workup at all.

PMID- 9170225
TI  - A combined antegrade and retrograde technique for reestablishing ureteral
      continuity.
AB  - Ureteral injuries are not uncommon and may lead to ureteral stricture, complete
      obliteration, or urinary fistula. Traditionally, open surgical repair was
      required to reestablish ureteral continuity. With the development of improved
      instrumentation and technique, it is now possible to treat these injuries
      endoscopically. Endoscopic ureteroureterostomy has been demonstrated to be an
      effective means of treating ureteral strictures and obliterated segments of the
      ureter. We describe a combined ureteroscopic and fluoroscopic technique to
      reestablish ureteral integrity. Using this technique we have successfully treated
      two patients with ureteral injuries. The first patient had a ureterovaginal
      fistula that occurred after a hysterectomy. The second patient had a completely
      obstructed distal ureter. These cases and the techniques used to successfully
      manage them are described.

PMID- 9170226
TI  - Laparoscopic evaluation and management of a child with ambiguous genitalia,
      ectopic spleen, and Meckel's diverticulum.
AB  - Laparoscopy may be helpful in the evaluation and management of the child with
      intersex. Laparoscopic excision of dysgenetic gonads may be necessary due to the
      increased risk of malignancy. Residual mullerian duct structures are removed to
      prevent symptomatic complications at puberty. We present the case of a
      laparoscopic evaluation and management of a 46XY child with ambiguous genitalia,
      as well as the laparoscopic management of two unrelated anomalies discovered at
      the time of surgery.

PMID- 9170227
TI  - Intracranial metastatic adenocarcinoma of the prostate presenting as visual
      disturbance.
AB  - We report two cases of intracranial metastatic adenocarcinoma of the prostate
      that presented with visual disturbance. The two patients had no prior history of
      prostate cancer and both underwent invasive neurosurgical procedures. Progressive
      neurological decline mandated craniotomy in one patient and the other patient
      underwent transphenoidal surgery for biopsy. Androgen deprivation therapy was
      instituted postoperatively for both patients when prostate cancer was determined
      to be the source of the metastatic lesions.

PMID- 9170228
TI  - Minimally invasive management of the calcified ureteral stent.
AB  - The double "J" ureter stent has become one of the most basic and valuable tools
      in urology, but it can cause complications. Stent encrustation is one of its most
      difficult complications to manage. An evaluation and treatment algorithm that
      stratifies the treatment based upon the function of the stented kidney and the
      presence or absence of concomitant ureteral obstruction is presented. Minimally
      invasive surgery using ESWL and cystolitholapaxy is recommended as the first line
      of treatment of the extensively encrusted ureteral stent when the kidney has
      greater than 10% function.

PMID- 9170229
TI  - A new role for WHO in emergencies.

PMID- 9170230
TI  - Health sector approach to vulnerability reduction and emergency preparedness.
AB  - Vulnerability is increasing year by year. Statistics show that not only are the
      human and economic costs of emergencies and disasters increasing, but that the
      cost of relief assistance has increased 10-fold in the last 11 years. Relief
      assistance alone can lead to increased vulnerability, by reducing development
      assistance and leading to further social crises The concept of vulnerability
      consist of two aspects, susceptibility and resilience; vulnerability reduction
      aims to reduce susceptibility to hazards and increase community resilience to
      emergencies. Vulnerability reduction involves vulnerability assessment, hazard
      prevention and mitigation, and emergency preparedness. Vulnerability reduction
      aims to decrease community susceptibility and increase community resilience, and
      can focus on emergencies thus preventing many disasters. Vulnerability reduction
      protects human development, and prepared communities can maintain and improve
      their level of development. Vulnerability reduction is the responsibility of all,
      including the health sector, and all sectors at all levels must assist
      communities to participate in reducing vulnerability. The health sector work in
      vulnerability reduction requires coordination at all levels within a country. WHO
      has been assisting in this work at the international, regional and country levels
      for many years. There is a need for statistical indicators of vulnerability and
      the harm caused by major emergencies. Data from these indicators will assist in
      monitoring and evaluating vulnerability reduction, and targeting communities at
      risk.

PMID- 9170231
TI  - Disasters in Africa: old and new hazards and growing vulnerability.
AB  - Disasters occur when hazards and vulnerability meet. Out of 100 disasters
      reported worldwide, only 20 occur in Africa, but Africa suffers 60% of all
      disaster-related deaths. This is probably due to the type of hazards that affect
      this continent, to under-reporting, and to the fact that under the circumstances
      prevailing in Africa, it is easy for any disaster to escalate and multiply its
      impact. Africa's natural hazards are mainly epidemics, endemic diseases, drought,
      floods, agricultural pests and bush fires, but some areas are also susceptible to
      earthquakes, cyclones and volcanic eruptions. The natural hazards interact with
      manmade ones, such as armed conflicts, air, road and railway incidents, other
      industrial hazards such as mining accidents, chemical spills, etc., and with
      widespread vulnerability. The context is one of rapid population growth, forced
      movements of population, environmental degradation, precarious urbanization, food
      insecurity, poverty, fragile economies, infrastructures and institutions, and
      cultural and political instability. The 53 countries of the continent are highly
      susceptible and vulnerable and their 761,390,000 people are exposed to both
      natural and manmade hazards. Through complex causal chains, disasters affect
      people directly and indirectly. In the first 6 months of 1996, meningitis had
      already killed 5,000 people. Throughout Africa, there are 500,000 measles
      associated deaths each year; the direct and indirect costs of malaria are
      estimated at US$ 1.7 billion per year. In June 1996 food emergencies were looming
      in 14 African countries with 22 million people facing direct food shortages.
      Since 1980, conflicts have caused at least 3.7 million excess deaths and cost the
      Region about US$ 13 billion per year. Wars have destroyed 70% of the health
      network of some countries, and have left behind 30-40 million landmines, making
      Africa the most mine-infested continent in the world.

PMID- 9170232
TI  - Sustaining, protecting and promoting public health in Bosnia and Herzegovina.
AB  - Four years of war in Bosnia and Herzegovina have severely damaged the health care
      system and destroyed basic infrastructures. Yet in spite of these conditions and
      the reappearance of several "dormant" diseases, no major fatal disease outbreaks
      have occurred. Morbidity and mortality due to infectious diseases have remained
      surprisingly low. This article explores some of the reasons why this potentially
      enormous public health disaster was avoided. Public health interventions can
      generally be considered the outcome of two components: knowledge and action. War
      situations inhibit thorough or ideal data collection and therefore the balance
      between knowledge and action must be tipped towards the latter. In Bosnia and
      Herzegovina, the WHO/national health monitoring system maintained a sufficient
      level of surveillance so as to provide early detection of significant threats to
      health. As the lead health agency in the conflict, WHO applied several health
      monitoring strategies. Major fatal epidemics were avoided because health workers
      have become increasingly scientific in predicting epidemics in war situations and
      formulating the steps necessary to limit them. Some of the preventive
      interventions applied in Bosnia and Herzegovina to reduce the impact of
      infectious diseases are discussed.

PMID- 9170233
TI  - SUMA (Supply Management Project), a management tool for post-disaster relief
      supplies.
AB  - Frequently in the wake of disasters, large amounts of humanitarian supplies
      arrive from multiple sources within the country or from abroad. Only a portion of
      these donations actually responds to specific requests from the affected country.
      A significant part consists of unsolicited donations whose value--in terms of
      meeting immediate, life-threatening needs--is questioned by many disaster
      managers. In 1990, WHO initiated a supply management project, known as "SUMA", to
      provide national authorities with a management tool and the skills to sort and
      inventory large amounts of relief supplies in a short period of time. It is a
      technical cooperation programme to assist the local coordinating agency to get an
      accurate picture of what is potentially available in the affected area, and to
      sort the most valuable relief items from those of doubtful usefulness. National
      authorities have developed their SUMA teams in many situations, both in Latin
      America and the Caribbean; this article describes three of these experiences. A
      flood in Costa Rica, in 1995, where the Red Cross assumed national responsibility
      for managing relief supplies donated locally. The earthquake in Paez, Colombia,
      also in 1995, where the National Disaster Committee activated SUMA for all
      supplies sent to the disaster area, with the exception of specialized health
      shipments channelled through the Ministry of Health. In Haiti, in 1994, a complex
      disaster was compounded by a tropical storm. All civilian supplies arriving at
      the airport were processed by the SUMA team which included customs officers among
      its members. The traditional problem of unsorted and inappropriate supplies,
      noted in most international disasters, seems to have been negligible, a trend
      which can perhaps be credited to 20 years of preparedness activities in Latin
      America and the Caribbean. The superficial analysis of the data underlines the
      potential for operational research on the standardized databases generated by
      SUMA.

PMID- 9170234
TI  - Disaster preparedness: institutional capacity building in the Americas.
AB  - Latin American and Caribbean countries are prone to natural, technological and
      "complex" disasters. This vulnerability to catastrophic events led the region to
      undertake the long journey away from an ad hoc response towards institutional
      preparedness and, more recently, to disaster prevention and mitigation. This
      article attempts to outline the definitions and basic principles of institutional
      emergency preparedness, including reliance on the more effective use of existing
      resources, rather than establishment of special stockpiles and equipment; the
      critical importance of general participation and awareness; and the
      interrelationship of the health sector with others and the potential for
      leadership. How to assess the level of preparedness is discussed. Stress is
      placed on the fact that preparedness is traditionally confused with the existence
      of a written disaster plan. Preparedness should be seen as a never-ending,
      complex process that can only be assessed through an in-depth review of
      coordination, planning, training and logistic elements. There is also a
      fundamental distinction between preparedness, i.e., "getting ready to respond"
      and disaster prevention/mitigation, which aims to reduce the health impact. The
      latter calls for the collaboration of engineers, architects, planners and
      economists with the health sector. It is illustrated by the regional initiative
      in the Americas to reduce the physical vulnerability of hospitals to earthquakes
      and hurricanes. In spite of the encouraging achievements, much remains to be
      done. Weak areas include preparedness for technological disasters, and a true
      inter-country preventive approach to common disasters across borders. Electronic
      communications through the Internet will also help to suppress borders and
      boundaries, contributing to a truly collective approach to emergency preparedness
      and disaster relief coordination.

PMID- 9170235
TI  - Impact of Hurricane Luis on the health services of Antigua and Barbuda.
AB  - Antigua and Barbuda, located in the Caribbean, was one of the countries most
      affected by Hurricane Luis in 1995. Electricity, water supply and health
      facilities were disrupted for several weeks. Inadequate criteria at the design
      stages, unsound structural design, and lack of maintenance of building
      components, are some of the reasons that damage was so severe. The main hospitals
      and 6 health facilities were destroyed and flooded and most of the medical staff
      had to cope with their own damaged houses. Although the knowledge and materials
      are available to reduce the losses caused by hurricanes, building codes are not
      reinforced by laws and preventive maintenance to protect health care facilities
      from natural hazard damage is not usually budgeted for. The additional cost of
      making a single or two-storey health facility almost invulnerable to future
      catastrophe in a hurricane is only 2% in initial capital cost and becomes
      negligible when spread over the life of a building. The effort of UN
      International Decade for Natural Disasters (IDNDR) directed towards disaster
      mitigation should be increased over the remainder of the decade to ensure that
      standards are respected and building codes are mandatory.

PMID- 9170236
TI  - The effects of volcanoes on health: preparedness in Mexico.
AB  - The article reviews the most important aspects of volcanic eruptions and presents
      a summary of the harmful materials they emit. The main health effects can be
      classified as either physical (trauma, respiratory diseases, etc.) or
      psychological (depression, anxiety, nightmares, neurosis, etc.). Popocatepetl,
      the most famous active volcano in Mexico, lies on the borders of the States of
      Mexico, Puebla and Morelos. In 1993, seismic activity intensified, as did as the
      emission of fumaroles, followed in December 1994 by moderate tremors and strong
      emissions of gases and ash. In 1996, a number of seismic events led to an
      unexpected explosion. A daily emission of 8,000 to 15,000 tonnes of sulfur
      dioxide has been measured. Popocatepetl is located in a densely populated region
      of Mexico. A complex network to monitor the volcano using sophisticated equipment
      has been set up, including visual surveillance, seismic, geochemical and geodesic
      monitoring. An early warning system (SINAPROC/CENAPRED) has been developed to
      keep the population permanently informed. The warning system uses colour codes:
      green for normal, yellow for alert, and red for warning and evacuation. An
      emergency plan has been prepared, including evacuation and preparation for
      medical centres and hospitals in the region, as well as intense public
      information campaigns.

PMID- 9170237
TI  - Main scientific results of the WHO International Programme on the Health Effects
      of the Chernobyl Accident (IPHECA).
AB  - Scientific results obtained within the WHO International Programme on the Health
      Effects of the Chernobyl Accident (IPHECA) have confirmed the increase of thyroid
      cancer cases in children who were exposed to radiation due to the accident in
      1986. In the zones under surveillance in Belarus, the Russian Federation and
      Ukraine, the general morbidity for leukaemia and related diseases did not undergo
      a significant change after the accident. Accident recovery workers
      ("liquidators") are an especially high-risk group and need further medical follow
      up.

PMID- 9170238
TI  - Mental health under war conditions during the 1991-1995 war in the former
      Yugoslavia.
AB  - If this war were a "peace time disaster" it is estimated that more than one
      million people would be in need of assistance due to mental health issues. The
      estimated helping capacity, however, can cover only a small proportion of the
      need. This imbalance may create a severe threat to the mental health of the war
      torn population in a medium- and long-term perspective. Complications related to
      war-trauma-induced stress disorders may give rise to significant increases in
      alcohol and drug abuse, domestic and criminal violence, suicides, homicides and
      chronic mental illness. This article outlines the international efforts to
      include psychosocial and mental health interventions as part of the emergency
      assistance programme. Special emphasis is directed at the development of the new
      WHO Regional Model on Mental Health. The model is a coordinated set of mental
      health activities for a defined geographical area with a population of 300,000
      400,000 inhabitants. The key elements are: coordination, collection of background
      data ("war-time epidemiology"), capacity building and self-empowerment of local
      professionals at all levels, as well as a community-oriented approach to mental
      health care and primary health care. A new structure to achieve sustainability
      and continuity of preventive mental health interventions, the European University
      Centre for Mental Health and Human Rights, is proposed for the medium- and long
      term perspective of assistance.

PMID- 9170239
TI  - Standardization of health relief items needed in the early phase of emergencies.
AB  - Concepts, ideas and advocacy for standardization of medical materials have been
      in existence for over a hundred years and until 1957 were the domain of the Red
      Cross Movement. Following the Second World War there emerged both national and
      international organizations concerned with standardization of medical materials.
      The Gulf War brought deficiencies in emergency relief to the attention of the
      United Nations System and one of the consequences of this was the decision to
      standardize all emergency relief items needed in the early phase of emergencies.
      Standardization of health relief items made up one part of this process.

PMID- 9170240
TI  - Refugees: do not forget the basics.
AB  - This article describes the main challenges faced by relief workers in meeting the
      needs of refugees in terms of their health and nutritional status. The main
      causes of refugee deaths in "emergencies" have been documented and identified.
      This has allowed the definition of technical principles for health interventions
      in refugee settings: a multi-sectoral approach; involving the refugees; meeting
      specific needs of refugee children and women; instituting a simple and reliable
      health information system; and ensuring proper management and coordination among
      all partners. Two examples selected from UNHCR field operations illustrate how
      important it is to adhere to the basic technical principles. Finally, the article
      also emphasizes that health assistance in refugee situations takes place in a
      context which is complex and comprises many variables. In addition to their
      qualifications and experience, health professionals must also be aware of the
      global dynamics of a conflict situation. Their leading principle should be that
      all human beings have the right to appropriate health care.

PMID- 9170241
TI  - UNICEF's rich history in emergency response.
AB  - When conflict erupts or natural disasters strike, UNICEF's challenge is to
      provide for the emergency needs of civilians, especially women and children, who
      are caught in the crossfire or plagued by the drought or swept away by the flood.
      When emergency situations arise, threatening to derail UNICEF's ongoing work in a
      country, the challenge is to adapt programmes to better address the changing
      needs of the affected population. UNICEF's goal in all countries undergoing
      emergencies is to build on the work already done to lay the foundation for long
      term peace and progress. In most emergency cases, certain core interventions are
      applied to meet basic needs, including health (UNICEF's largest activity in
      emergencies), water supply and sanitation, education, nutrition, community
      development, advocacy and initiatives addressing the special needs of women and
      children. Specific programmes for unaccompanied children, women's reproductive
      health, child soldiers, land-mine awareness and child prisoners are also employed
      in many emergency situations. UNICEF works towards the day when children and
      women no longer face acute threats to their survival and development; but until
      such time as natural disasters and man-made conflict no longer pose threats to
      them, UNICEF remains committed to the range of activities required to ensure
      their protection and well-being.

PMID- 9170242
TI  - Childhood homicide, suicide, and firearm deaths: an international comparison.
AB  - This article is intended to provide a better understanding of the incidence of
      violent deaths among children under 15 years of age in highly industrialized
      countries/areas. We found that rates of violent childhood deaths are not uniform
      in the industrialized world and that rates in the United States greatly exceed
      those in the other countries and areas. In fact, total firearm deaths among
      children are 12 times higher in the United States than in all of the other
      countries or areas combined; childhood homicide rates are 5 times higher; and
      childhood suicide rates are twice as high. Five countries or areas, 3 of which
      are in Asia, reported no firearm deaths among children under 15 years old. These
      findings suggest the value of conducting further research to explore these cross
      national differences.

PMID- 9170243
TI  - Regulation of phosphotransferases in glucose- and xylose-fermenting yeasts.
AB  - This research examined the titers of hexokinase (HK), phosphofructokinase (PFK),
      and xylulokinase (XUK) in Saccharomyces cerevisiae and two xylose fermenting
      yeasts, Pachysolen tannophilus and Candida shehatae, following shifts in carbon
      source and aeration. Xylose-grown C. shehatae, glucose-grown P. tannophilus, and
      glucose-grown S. cerevisiae, had the highest specific activities of XUK, HK, and
      PFK, respectively. XUK was induced by xylose to moderate levels in both P.
      tannophilus and C. shehatae, but was present only in trace levels in S.
      cerevisiae. HK activities in P. tannophilus were two to three fold higher when
      cells were grown on glucose than when grown on xylose, but HK levels were less
      inducible in C. shehatae. The PFK activities in S. cerevisiae were 1.5 to 2 times
      higher than in the two xylose-fermenting yeasts. Transfer from glucose to xylose
      rapidly inactivated HK in P. tannophilus, and transfer from xylose to glucose
      inactivated XUK in C. shehatae. The patterns of induction and inactivation
      indicate that the basic regulatory mechanisms differ in the two xylose fermenting
      yeasts.

PMID- 9170244
TI  - Expression of Ascaris suum malic enzyme in a mutant Escherichia coli allows
      production of succinic acid from glucose.
AB  - The malic enzyme gene of Ascaris suum, was cloned into the vector pTRC99a in two
      forms encoding alternative amino-termini. The resulting plasmids, pMEA1 and
      pMEA2, were introduced into Escherichia coli NZN111, a strain that is unable to
      grow fermentatively because of inactivation of the genes encoding pyruvate
      dissimilation. Induction of pMEA1, which encodes the native animoterminus, gave
      better overexpression of malic enzyme, approx 12-fold compared to uninduced
      cells. Under the appropriate culture conditions, expression of malic enzyme
      allowed the fermentative dissimilation of glucose by NZN111. The major
      fermentation product formed in induced cultures was succinic acid.

PMID- 9170246
TI  - Production of alpha-terpineol from Escherichia coli cells expressing thermostable
      limonene hydratase.
AB  - The genes encoding a thermostable limonene hydratase have been located on a
      cloned fragment in Escherichia coli conferring growth on limonene and production
      of the monoterpenes perillyl alcohol and alpha-terpineol. Whole cell
      bioconversion studies at elevated temperature employing both an aqueous phase and
      neat limonene phase demonstrated significant production of alpha-terpineol with
      additional production of carvone.

PMID- 9170245
TI  - Asparaginase II of Saccharomyces cerevisiae. GLN3/URE2 regulation of a
      periplasmic enzyme.
AB  - The production of some extracellular enzymes is known to be negatively affected
      by readily metabolized nitrogen sources such as NH4+ although there is no
      consensus regarding the involved mechanisms. Asparaginase II is a periplasmic
      enzyme of Saccharomyces cerevisiae encoded by the ASP3 gene. The enzyme activity
      is not found in cells grown in either ammonia, glutamine, or glutamate, but it is
      found in cells that have been subjected to nitrogen starvation or have been grown
      on a poor source of nitrogen such as proline. In this report it is shown that the
      formation of this enzyme is dependent upon the functional GLN3 gene and that the
      response to nitrogen availability is under the control of the URE2 gene product.
      In this respect the expression of ASP3 is similar to the system that regulates
      the GLN1, GDH2, GAP1, and PUT4 genes that codes for glutamine synthetase, NAD
      linked glutamate dehydrogenase, general amino-acid permease, and high affinity
      proline permease, respectively.

PMID- 9170247
TI  - Fermentation of biomass-derived glucuronic acid by pet expressing recombinants of
      E. coli B.
AB  - The economics of large-scale production of fuel ethanol from biomass and wastes
      requires the efficient utilization of all the sugars derived from the hydrolysis
      of the heteropolymeric hemicellulose component of lignocellulosic feedstocks.
      Glucuronic and 4-O-methyl-glucuronic acids are major side chains in xylans of the
      grasses and hardwoods that have been targeted as potential feedstocks for the
      production of cellulosic ethanol. The amount of these acids is similar to that of
      arabinose, which is now being viewed as another potential substrate in the
      production of biomass-derived ethanol. This study compared the end-product
      distribution associated with the fermentation of D-glucose (Glc) and D-glucuronic
      acid (GlcUA) (as sole carbon and energy sources) by Escherichia coli B (ATCC
      11303) and two different ethanologenic recombinants--a strain in which pet
      expression was via a multicopy plasmid (pLOI297) and a chromosomally integrated
      construct, strain KO11. pH-stat batch fermentations were conducted using a
      modified LB medium with 2% (w/v) Glc or GlcUA with the set-point for pH control
      at either 6.3 or 7.0. The nontransformed host culture produced only lactic acid
      from glucose, but fermentation of GlcUA yielded a mixture of ethanol, acetic, and
      lactic acids, with acetic acid being the predominant end-product. The ethanol
      yield associated with GlcUA fermentation by both recombinants was similar, but
      acetic acid was a significant by-product. Increasing the pH from 6.3 to 7.0
      increased the rate of glucuronate fermentation, but it also decreased the ethanol
      mass yield from 0.22 to 0.19 g/g primarily because of an increase in acetic acid
      production. In all fermentations there was good closure of the carbon mass
      balance, the exception being the recombinant bearing plasmid pLOI297 that
      produced an unidentified product from GlcUA. The metabolism of GlcUA by this
      metabolically engineered construct remains unresolved. The results offered
      insights into metabolic fluxes and the regulation of pyruvate catabolism in the
      wild-type and engineered strains. End-product distribution for metabolism of
      glucuronic acid by the nontransformed, wild-type E. coli B and recombinant strain
      KO11 suggests that the enzyme pyruvate-formate lyase is not solely responsible
      for the production of acetylCoA from pyruvate and that derepressed pyruvate
      dehydrogenase may play a significant role in the metabolism of GlcUA.

PMID- 9170248
TI  - Performance of coimmobilized yeast and amyloglucosidase in a fluidized bed
      reactor for fuel ethanol production.
AB  - The performance of coimmobilized Saccharomyces cerevisiae and amyloglucosidase
      (AG) was evaluated in a fluidized-bed reactor. Soluble starch and yeast extracts
      were used as feed stocks. Conversion of soluble starch streams to ethanol has
      potential practical applications in corn dry and wet milling and in developmental
      lignocellulosic processes. The biocatalyst performed well, and demonstrated no
      significant loss of activity or physical integrity during 10 wk of continuous
      operation. The reactor was easily operated and required no pH control. No
      operational problems were encountered from bacterial contaminants even though the
      reactor was operated under nonsterile conditions over the entire course of
      experiments. Productivities ranged between 25 and 44 g ethanol/L/h/. The
      experiments demonstrated that ethanol inhibition and bed loading had significant
      effects on reactor performance.

PMID- 9170249
TI  - Immobilization of glucose oxidase with the blend of regenerated silk fibroin and
      poly(vinyl alcohol) and its application to a 1,1'-dimethylferrocene-mediating
      glucose sensor.
AB  - The structure and properties of the blend of regenerated silk fibroin (RSF) and
      poly(vinyl alcohol) (PVA) were investigated. The two polymers in the blend are in
      the state of phase segregation. Infrared (IR) spectra indicate that the RSF in
      the blend maintains its intrinsic properties, thus, ethanol treatment can
      transfer silk I structure of RSF to silk II structure. The water absorption
      property and mechanical property of the blend are improved in comparison with
      those of RSF. The blend maintains the major merit of RSF, that is, it can
      immobilize glucose oxidase on the basis of the conformational transition from
      silk I structure to silk II structure. The properties of the immobilized enzyme
      are examined. Moreover, the second generation of glucose sensor based on the
      immobilized enzyme is fabricated and it has a variety of advantages including
      easy maintenance of enzyme, simplicity of construction, fast response time and
      high stability.

PMID- 9170250
TI  - Separation of alpha-amylase by reversed micellar extraction. Effect of solvent
      type and cosolvent concentration on the transfer process.
AB  - The recovery of alpha-amylase from the crude enzyme preparation by the reversed
      micellar liquid-liquid extraction was investigated. The reversed micellar
      solution was formed by dissolving a cationic surfactant Aliquat 336 in six
      different alkanes (cyclohexane, n-hexane, isooctane, n-octane, n-decane, and n
      dodecane) respectively with addition of a cosolvent n-octanol. It was found that
      a minimal quantity of n-octanol was needed for Aliquat 336 to dissolve in apolar
      solvent and form reversed micelles. Furthermore, this minimal amount of n-octanol
      needed was found to be different when Aliquat 336 was dissolved in different
      alkanes. It tended to increase with the number of carbon atoms in alkane and also
      depended on the solvent structure. During the forward extraction process, it was
      revealed that a high value of solubilization of protein in Aliquat 336 reversed
      micelles could be achieved when four out of the six alkanes (cyclohexane, n
      hexane, isooctane, n-octane) were used as the solvent for Aliquat 336. After a
      full forward and backward extraction cycle, however, a high recovery of both the
      protein mass and alpha-amylase activity in the stripping solution could be
      obtained only when two out of the six alkanes (n-hexane and isooctane) were used
      as the solvent for Aliquat 336. When n-hexane and isooctane were used as the
      solvent for Aliquat 336, up to 80% of the total alpha-amylase activity in the
      crude enzyme preparation could be recovered at the end of extraction cycle,
      meanwhile alpha-amylase could be concentrated about 1.4-fold. In the cases of
      other four alkanes (cyclohexane, n-octane, n-decane, and n-dodecane) as solvent,
      most of the alpha-amylase activity in the crude enzyme preparation would be
      denatured after an extraction cycle.

PMID- 9170252
TI  - Conjugation of the Bowman-Birk soybean proteinase inhibitor with
      hydroxyethylstarch.
AB  - The classical Bowman-Birk soybean proteinase inhibitor was modified by
      hydroxyethylstarch. The modified inhibitor retained the capacity for simultaneous
      binding of trypsin and human leukocyte elastase. The inhibition constants, Ki, of
      bovine trypsin, alpha-chymotrypsin and human leukocyte elastase (HLE) increased
      not more than 10-, 1.5-, and 20-fold, respectively, on modification of the
      inhibitor. The less effective inhibition is presumably due to the steric
      hindrance brought about by the conjugation with polysaccharide molecules. The
      results obtained indicate the pronounced structure differences of the binding
      regions for trypsin and chymotrypsin/leukocyte elastase in the modified
      preparation.

PMID- 9170251
TI  - Mechanism and potential applications of bio-ligninolytic systems in a CELSS.
AB  - A large amount of inedible plant material, generated as a result of plant growth
      in a Controlled Ecological Life Support System (CELSS), should be pretreated and
      converted into forms that can be recycled on earth as well as in space. The main
      portion of the inedible biomass is lignocellulosic material. Enzymatic hydrolysis
      of this cellulose would provide sugars for many other uses by recycling carbon,
      hydrogen, oxygen, and nitrogen through formation of carbon dioxide, heat, and
      sugars, which are potential foodstuffs. To obtain monosaccharides from cellulose,
      the protective effect of lignin should be removed. White-rot fungi degrade lignin
      more extensively and rapidly than other microorganisms. Pleurotus ostreatus
      degrades lignin effectively, and produces edible and flavorful mushrooms that
      increase the quality and nutritional value of the diet. This mushroom is also
      capable of metabolizing hemicellulose, thereby providing a food use of this
      pentose containing polysaccharide. This study presents the current knowledge of
      physiology and biochemistry of primary and secondary metabolisms of
      basidiomycetes, and degradation mechanism of lignin. A better understanding of
      the ligninolytic activity of white-rot fungi will impact the CELSS Program by
      providing insights on how edible fungi might be used to recycle the inedible
      portions of the crops.

PMID- 9170253
TI  - Characterization of a monoclonal antibody that specifically inhibits pullulanase
      activity of Bacillus circulans amylase-pullulanase enzyme.
AB  - A monoclonal antibody (MAb) against amylase pullulanase enzyme from Bacillus
      circulans, which hydrolyzes not only the alpha-1,6-glycosidic linkage but also
      the alpha-1,4-glycosidic linkage to the same extent, has been produced by the
      fusion of BALB/c mouse spleen cells immunized with the native enzyme and
      P3x63Ag8U1 myeloma cells, and examined for inhibition of pullulanase activity in
      order to characterize the catalytic site of the pullulanase. The MAb recognizes
      active enzyme, but not the SDS-denatured or heat-inactivated protein, indicating
      that the antibody is highly conformational-dependent, specific for active enzyme.
      The antibody inhibited the pullulanase activity, but not amylase activity. The
      monoclonal antibody immunoblotted the enzyme and immunoprecipitated the enzyme.
      The immunoprecipitation was inhibited in the presence of substrate, pullulan, and
      the MAb competitively inhibited the binding of pullulan to the enzyme. The MAb,
      therefore, recognizes the pullulan-binding site of the enzyme. Kinetic analysis
      showed that the MAb inhibited pullulanase activity with inhibition constant (Ki)
      of 0.77 microgram/mL, providing evidence that the antibody decreases the
      catalytic rate of enzyme activity and has an effect on substrate binding. These
      results strongly confirm the previous observations that APE may have two
      different active sites responsible for the expression of amylase and pullulanase
      activities (Kim, C.H. and Kim, Y.S. Eur. J. Biochem. 1995, 227, 687-693).

PMID- 9170254
TI  - Purification and characterization of the D-hydantoinase from Bacillus circulans.
AB  - A D-hydantoinase (5,6-dihydropyrimidine amidohydrolase) was purified to
      homogeneity from Bacillus circulans. Purification of two hundred forty-three-fold
      was achieved with an overall yield of 12%. The relative molecular mass of the
      native enzyme is 212,000 and that of the subunit is 53,000. This enzyme is an
      acidic protein with an isoelectric point of 4.55. The enzyme is sensitive to
      thiol reagent and requires metal ions for its activity. The optimal conditions
      for the hydantoinase activity are pH 8.0-10.0 and a temperature of 75 degrees C.
      The enzyme is the most stable in a pH range of 8.5-9.5 and up to 60 degrees C.
      The enzyme is significantly stable not only at high temperatures but also on
      treatment with protein denaturant SDS. These remarkable properties are used for
      the purification procedure.

PMID- 9170255
TI  - Lignin biodegradation by the ascomycete Chrysonilia sitophila.
AB  - The lignin biodegradation process has an important role in the carbon cycle of
      the biosphere. The study of this natural process has developed mainly with the
      use of basidiomycetes in laboratory investigations. This has been a logical
      approach since most of the microorganisms involved in lignocellulosic degradation
      belong to this class of fungi. However, other microorganisms such as ascomycetes
      and also some bacteria, are involved in the lignin decaying process. This work
      focuses on lignin biodegradation by a microorganism belonging to the ascomycete
      class, Chrysonilia sitophila. Lignin peroxidase production and characterization,
      mechanisms of lignin degradation (lignin model compounds and lignin in wood
      matrix) and biosynthesis of veratryl alcohol are outstanding. Applications of C.
      sitophila for effluent treatment, wood biodegradation and single-cell protein
      production are also discussed.

PMID- 9170256
TI  - Purification and characterization of thermostable D-hydantoinase from
      thermophilic Bacillus stearothermophilus SD-1.
AB  - A thermostable D-hydantoinase of thermophilic Bacillus stearothermophilus SD-1
      was purified to homogeneity using an immuno-affinity chromatography. The affinity
      chromatography that employed polyclonal antibody immobilized on Sepharose 4B was
      simple to operate and gave a purification yield of 60% of enzyme activity.
      Molecular mass of the enzyme was determined to be about 133.9 kDa by gel
      filtration chromatography and the molecular mass of the subunit was 54 kDa on SDS
      PAGE. Mass spectrometric analyses were also performed for the determination of
      the molecular mass of the native enzyme and its subunit. The apparent molecular
      masses were 51.1 and 102.1 kDa for the subunit and native enzyme, respectively.
      Based on the molecular masses determined by these two methods, it is suggested
      that the D-hydantoinase exists as a dimeric conformation in the cell. Isoelectric
      pH of the enzyme was observed to be 4.47. It was found that the enzyme requires
      one manganese ion per molecule of enzyme for the activity. The optimal pH and
      temperature for the catalytic activity were about 8.0 and 65 degrees C,
      respectively. The half-life of the enzyme was estimated to be 30 min at 80
      degrees C, confirming that the enzyme purified is one of the most thermostable D
      hydantoinase reported so far. Kinetic constants of the enzyme for different
      substrates were also determined.

PMID- 9170257
TI  - Antigen-antibody binding kinetics for biosensor applications. A dual-fractal
      analysis.
AB  - The diffusion-limited binding kinetics of antigen (or antibody) in solution to
      antibody (or antigen) immobilized on a biosensor surface is analyzed within a
      fractal framework. The fit obtained by a dual-fractal analysis is compared with
      that obtained from a single-fractal analysis. In some cases, the dual-fractal
      analysis provides an improved fit when compared with a single-fractal analysis.
      This was indicated by the regression analysis provided by Sigmaplot (San Rafael,
      CA). These examples are presented. It is of interest to note that the state of
      disorder (or the fractal dimension) and the binding rate coefficient both
      increase (or decrease, a single example is presented for this case) as the
      reaction progresses on the biosensor surface. For example, for the binding of
      monoclonal antibody MAb 49 in solution to surface-immobilized antigen, a 90.4%
      increase in the fractal dimension (Df1 to Df2) from 1.327 to 2.527 leads to an
      increase in the binding rate coefficient (k1 to k2) by a factor of 9.4 from 11.74
      to 110.3. The different examples analyzed and presented together provide a means
      by which the antigen-antibody reactions may be better controlled by noting the
      magnitude of the changes in the fractal dimension and in the binding rate
      coefficient as the reaction progresses on the biosensor surface.

PMID- 9170258
TI  - The culture of chicken embryo fibroblast cells on microcarriers to produce
      infectious bursal disease virus.
AB  - The cultures of chicken embryo fibroblast (CEF) cells in flasks, spinner bottles,
      and bioreactors were studied. The growth and metabolism characteristics of CEF
      cells and the feasibility of the CEF cell culture in bioreactor were
      investigated. The plating process of the CEF cells on GT-2 microcarriers in
      spinner bottles was studied, and a plating kinetic model was presented. The
      culture of CEF cells in 1.5 L CelliGen bioreactor to produce infectious bursal
      disease virus (IBDV) had met success. Whereas the additive microcarriers were fed
      during the culture, the cell density was increased 10 times as against seed cells
      adhering to microcarriers and the virus titer was as high as 7.5. All the
      aforementioned experimental results have laid the foundation for high density
      culture of CEF cells and process scale-up.

PMID- 9170259
TI  - Immobilization of whole-cell penicillin G acylase by entrapping within
      polymethacrylamide beads.
AB  - Escherichia coli ATCC 11105 containing the periplasmic penicillin G acylase was
      entrapped within a copolymer of methacrylamide and N,N'-methylenebisacrylamide. A
      solution of monomer that was made up from methacrylamide and N,N'
      methylenebisacrylamide dissolved in buffer was mixed with lyophilized cells and
      ammonium persulfate. This suspension was then pumped drop by drop into in soybean
      oil supplemented with 0.06% (v/v) 3-(dimethylamino)-propionitril. During
      submerging in the oil phase, the droplets were hardened and induced to polymerize
      within the droplets. Particles with a volume ranging from 0.013-0.017 mL per bead
      containing a biomass concentration up to 38.0 g/L were prepared. The optimal
      condition for the deacylation of penicillin G to 6-aminopencillanic acid (6-APA)
      catalyzed by the immobilized whole-cell penicillin G acylase was found to be 45
      degrees C and pH 8.0. Product inhibition of this enzyme by 6-APA could be
      eliminated by controlling pH value at 8 during the course of penicillin G
      hydrolysis using a pH-stat. Conversion determined by the pH-stat method were 0.3%
      higher than that by p-dimethylaminobenzaldehyde method. Cell concentration in the
      matrix was found to be an important factor influencing the maximum velocity and
      the specific activity retained in the matrix. A kinetic model, in which the mass
      transfer resistances as a result of external film mass transfer and pore
      diffusion were assumed to be negligible, could properly describe the hydrolysis
      of penicillin G by the cells entrapped within the polymethacylamide beads.

PMID- 9170260
TI  - Bacterial degradation of natural rubber: a privilege of actinomycetes?
AB  - Using natural rubber latex as the sole source of carbon and energy 50 rubber
      degrading bacteria were isolated. Out of those 50 isolates, 33 were identified as
      Streptomyces species and 8 as Micromonospora species. Screening of 1220 bacteria
      obtained from different culture collections revealed 46 additional rubber
      degrading bacteria (Streptomyces 31 strains, Micromonospora 5, Actinoplanes 3,
      Nocardia 2, Dactylosporangium 1, Actinomadura 1, unidentified 3). All rubber
      degrading isolates were identified as members of the actinomycetes, a large group
      of mycelium-forming Gram-positive bacteria. Interestingly no Gram-negative
      bacterium could be isolated. In most strains expression of extracellular rubber
      degrading enzymes was repressed by glucose and/or succinate. The reduction of the
      average molecular mass of solution-cast films of natural rubber from 640000 to
      25000 in liquid culture upon bacterial growth indicates the participation of an
      endo-cleavage mechanism of degradation.

PMID- 9170261
TI  - Isolation and characterization of a Listeria monocytogenes mutant strain
      hyperproducing virulence factors.
AB  - A mutant strain characterized by hyperproduction of a number of cell wall and
      supernatant proteins was isolated after N'methyl-N'-nitro-N-nitrosoguanidine
      treatment of Listeria monocytogenes strain NCTC10527. Several of these proteins
      were identified as virulence factors. When a wild-type strain was grown in the
      presence of activated charcoal it was shown to exhibit the same protein pattern
      as the isolated mutant.

PMID- 9170262
TI  - Divergent activity and function of superoxide dismutases in Pasteurella
      haemolytica serotypes A1 and A2 and Pasteurella trehalosi serotype T10.
AB  - Representative strains of Pasteurella haemolytica serotypes A1 and A2 and
      Pasteurella trehalosi serotype T10 were examined for the presence of superoxide
      dismutase. Visualisation of superoxide dismutase enzyme activity on
      polyacrylamide gels, and specific inhibition with potassium cyanide verified a
      copper/zinc (Cu/Zn) superoxide dismutase only in serotype A2 whereas serotypes A1
      and T10 showed other superoxide dismutase activity. Using a simple freeze-thaw
      method the cellular location of superoxide dismutase enzyme activity was
      determined in all three serotypes. In serotypes A1 and A2 but not T10 superoxide
      dismutases were located in the periplasm. The viability of serotypes A2 and T10
      cells in the presence of exogenous superoxide was unchanged over a 30 min period,
      whereas serotype A1 cells declined in viability between 15 and 30 min. Purified
      immunoglobulin from sheep convalescent serum did not reduce superoxide dismutase
      activity in the serotypes in an in vitro assay. The presence of this enzyme
      within the pasteurellae suggests a supportive role in the virulence of this major
      pathogen of ruminants.

PMID- 9170263
TI  - Cleavage of the synaptobrevin/vesicle-associated membrane protein (VAMP) of the
      mouse brain by the recombinant light chain of Clostridium botulinum type B toxin.
AB  - The light chain of Clostridium botulinum type B toxin was expressed in
      Escherichia coli using the expression vector pEt-3a containing phage T7 promoter.
      The expressed protein was then purified by DEAE-cellulose and phosphocellulose
      chromatography and the proteolytic activity of the purified light chain was
      studied. The purified recombinant light chain cleaved synaptobrevin when mixed
      with the mouse brain microsome and the proteolytic activity of the light chain
      was inhibited if a metal chelating agent such as EDTA or 2,2'-dipyridyl was
      added. The recombinant light chain cleaved synaptobrevin more effectively than
      the native type B toxin. When the native toxin was trypinized and was reduced
      with DTT, its proteolytic activity was similar to that of the recombinant light
      chain.

PMID- 9170264
TI  - PCR-RFLP analysis of the Cryptosporidium oocyst wall protein (COWP) gene
      discriminates between C. wrairi and C. parvum, and between C. parvum isolates of
      human and animal origin.
AB  - Cryptosporidium wrairi was isolated from guinea pigs during a spontaneous
      outbreak of cryptosporidiosis. Despite the morphological and antigenic
      similarities to C. parvum, C. wrairi displayed a different host range and site of
      infection and may represent a separate species or sub-species. We used the
      polymerase chain reaction to clone two distinct 550 bp-long DNA fragments, Wc-I
      and Wc-II, of the gene encoding the Cryptosporidium oocyst wall protein (COWP) of
      C. wrairi, which showed 98% identity to the C. parvum homologue. Within Wc-I,
      polymorphic Rsal restriction sites were used to develop a polymerase chain
      reaction-restriction fragment length polymorphism method able to distinguish C.
      wrairi from C. parvum and to identify two groups of C. parvum isolates
      differentially associated with animal and human infections.

PMID- 9170265
TI  - Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial
      vaginosis.
AB  - A unique coryneform bacterium was isolated from a patient with bacterial
      vaginosis. Chemotaxonomical investigations demonstrated that the unknown
      bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly
      lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily
      differentiated from the other members of the genus Corynebacterium. Comparative
      16S rRNA gene analysis revealed that the bacterium represented a new subline
      within the genus Corynebacterium for which the name Corynebacterium
      lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291).

PMID- 9170266
TI  - Characterization of Orientia tsutsugamushi isolated in Taiwan by
      immunofluorescence and restriction fragment length polymorphism analyses.
AB  - A total of 10 strains of Orientia tsutsugamushi were isolated from field rodents
      and chiggers in Taiwan, and characterized by immunofluorescence analysis with
      monoclonal antibodies and by restriction fragment length polymorphism analysis of
      the 56-kilodalton (kDa) protein gene. The isolates were divided into two groups
      consisting of 1 and 9 strains which showed some relation to Gilliam and Karp type
      strains, respectively. However, all these isolates possessed characteristics
      distinct not only from those of known prototype strains including Gilliam and
      Karp but also from all isolates from Japan. These findings suggest the existence
      of a large number of immunotypic and genotypic variants among the strains of O.
      tsutsugamushi, and the distribution of distinguishable strains in each area to
      which this species is endemic.

PMID- 9170267
TI  - Prevalence of the speA2 and speA3 alleles in Streptococcus pyogenes isolated from
      TSLS patients in Japan.
AB  - More than 100 cases have been identified as streptococcal toxic shock-like
      syndrome (TSLS) in Japan, since the first case was reported in 1993. Of 26 S.
      pyogenes isolates associated with TSLS, 69% were M-types 1 and 3. This study
      focused on speA alleles which were carried by all M-type 1 and 3 isolates and
      isolates of some other M-types, irrespective of sources. We sequenced the
      nucleotides of the relevant region of the speA allele in all of these isolates.
      Consistent with other reports, these M-type 1 and 3 isolates carried the speA2
      and speA3 alleles, respectively. Our results indicate that these two speA
      alleles, which were prevalent world-wide have been disseminating in Japan.

PMID- 9170268
TI  - Characterization of dnaA gene expression in Mycoplasma capricolum.
AB  - Expression of the dnaA gene in Mycoplasma capricolum was studied. The
      transcriptional start site was located 10 bp upstream from the putative
      translational initiation codon. Immunoblotting analysis revealed that DnaA
      protein was expressed at the levels significantly larger than those in
      Escherichia coli, and was localized mainly in the membrane. The transcriptional
      level of dnaA gene was reduced by inhibition of DNA synthesis with methyl
      methanesulfonate or mitomycin C, while the level of DnaA protein did not change.
      Reduction of protein synthesis did not significantly affect the total amount of
      DnaA protein, suggesting that the rates of synthesis and degradation of the
      protein are slow. These observations showed that the expression pattern of dnaA
      gene in M. capricolum is different from those of walled bacteria in some aspects.

PMID- 9170269
TI  - El Tor hemolysin of Vibrio cholerae O1 forms channels in planar lipid bilayer
      membranes.
AB  - We investigated the channel formation by El Tor hemolysin (molecular mass, 65
      kDa) of Vibrio cholerae O1 biotype El Tor in planar lipid bilayers. The El Tor
      hemolysin channel exhibited asymmetric and hyperbolic membrane current with
      increasing membrane potential, meaning that the channel is voltage dependent. The
      zero-current membrane potential measured in KCI solution showed that permeability
      ratio PK+/PCl- was 0.16, indicating that the channel is 6-fold more anion
      selective over cation. The hemolysin channel frequently flickered in the presence
      of divalent cations, suggesting that the channel spontaneously opens and closes.
      These data imply that the El Tor hemolysin damages target cells by the formation
      of transmembrane channels and, consequently, is the cause of osmotic cytolysis.

PMID- 9170270
TI  - Characterization of monoclonal antibodies for rapid identification of Actinomyces
      naeslundii in clinical samples.
AB  - The purpose of this study was to generate highly specific serological reagents
      for the quantitative identification of Actinomyces naeslundii in clinical
      samples, in particular dental plaque. Balb/c mice were immunized with pasteurized
      human A. naeslundii strains representing different genospecies and serotypes. Ten
      hybrid cell lines secreting monoclonal antibodies reactive with A. naeslundii
      were isolated and characterized. Antibody specificity was determined by indirect
      immunofluo-rescence and enzyme-linked immunosorbent assay using strains from 59
      species and by immunofluorescence analyses of supragingival plaque from 10
      gingivitis patients. Nine monoclonal antibodies reacted selectively with A.
      naeslundii, whereas one additionally bound to Actinomyces israelii. They
      recognized at least nine different epitopes with characteristic expression
      patterns among the test strains. Six clusters of antigenically unique or closely
      related strains could be distinguished. Clusters 1, 4, and 5 represented by 12,
      18, and 5 strains, respectively, comprised over 80% of the A. naeslundii strains
      tested. All reference strains for genospecies 1 grouped with cluster 1. Strains
      associated with genospecies 2 fell into clusters 4 and 5. Tests with mutant
      strains indicated that three monoclonal antibodies recognize type 2 and one type
      1 fimbriae of genospecies 2. Only four isolates grouped with clusters 2 and 3
      characterized by the expression of cluster-specific antigens. Interestingly,
      cluster 2 and 3 bacteria were markedly more abundant in vivo than indicated by
      their sparse representation in our strain collection. Overall, all but one of the
      new monoclonal antibodies should prove of value for the serological
      classification and rapid quantitative determination of A. naeslundii in clinical
      samples.

PMID- 9170271
TI  - Characterization of Bacillus subtilis mutants resistant to cold shock-induced
      autolysis.
AB  - Bacillus subtilis vegetative cells undergo autolysis when exposed to cold shock
      treatment. A mutant (CA1) resistant to cold shock was isolated, and its DNA was
      used for the transformation of B. subtilis 168AR. The transformant (TR1) and CA1
      had almost completely lost major vegetative autolysins (Cw1B and Cw1G) and
      motility, and showed a filamentous cell morphology during the exponential phase.
      Expression of the sigD-lacZ fusion was reduced in TR1. But the introduction of a
      SigD overproducing plasmid, pHYSigD, into TR1 led to a considerable increase in
      the amount of autolysin, a normal cell morphology (short rod), and the cold shock
      sensitive phenotype. However, motility was not restored in the transformant. The
      roles of pleiotropic genes in cold shock-induced autolysis are discussed.

PMID- 9170272
TI  - Nucleotide sequence of a nicking site of the Streptomyces plasmid pSN22
      replicating by the rolling circle mechanism.
AB  - A putative nicking site in the double strand origin (DSO) of the Streptomyces
      plasmid pSN22 was identified by comparing the nucleotide sequence of the DSO
      region with those of two other Streptomyces plasmids, pIJ101 and pJVI. A 7-bp
      sequence of this putative nicking site, 5'-CTTGGGA-3', was similar to the
      consensus sequence of the nicking site of the pC194 group of plasmids. When
      several point mutations were introduced into this 7-bp sequence, the
      transformation abilities of the mutant plasmid molecules for Streptomyces
      lividans were either reduced or lost. Southern hybridization analysis indicated
      that these mutant plasmids could not replicate in S. lividans, but were
      integrated into the chromosomal DNA.

PMID- 9170273
TI  - Analysis of functional domains of Vibrio parahaemolyticus thermostable direct
      hemolysin using monoclonal antibodies.
AB  - Neutralizing monoclonal antibodies (mAbs) against Vibrio parahaemolyticus
      thermostable direct hemolysin (TDH) were used in probing the functional domains
      of this toxin. While pre-incubation of TDH with mAb 2A-13C inhibited further
      binding of TDH to erythrocytes, pre-incubation with another mAb 1-24 did not,
      indicating that mAb 1-24 epitope resides in a domain which is not involved in
      binding of TDH to erythrocytes. On the other hand after binding to erythrocytes,
      TDH could react with mAb 1-24 but poorly with mAb 2A-13C, indicating that the mAb
      2A-13C epitope is masked, possibly by erythrocyte surface. As both antibodies are
      TDH-specific and do not react with TRH (TDH-related hemolysin), we used TDH/ TRH
      chimeric proteins to identify location of the epitopes for mAbs by inhibition
      ELISA as well as Western blotting. The results showed that the mAb 1-24 epitope
      resides on a region near the C-terminal of TDH (residues 99-139), while the mAb
      2A-13C epitope resides on the N-terminal (residues 1-31). All these results
      suggested that, in TDH, the N-terminal region may be involved in binding process
      while the region near C-terminal may be involved in postbinding process.

PMID- 9170274
TI  - Immotile phenotype of an Escherichia coli mutant lacking the histone-like protein
      HU.
AB  - The histone-like protein HU in Escherichia coli are encoded by the hupA and hupB
      genes. A hupA-hupB double deletion mutant has now been shown to express an
      immotile phenotype. The motility of hupA or hupB single mutants was similar to
      that of wild-type cells. SDS-polyacrylamide gel electrophoresis revealed that the
      amount of flagellin in the hupA-hupB double deletion mutant was markedly reduced
      compared with the wild-type strain suggesting that the immotile phenotype of the
      double deletion mutant is caused by a loss of flagella.

PMID- 9170275
TI  - Functional expression of the PHA synthase gene phaC1 from Pseudomonas aeruginosa
      in Escherichia coli results in poly(3-hydroxyalkanoate) synthesis.
AB  - The potential of the production of polyhydroxyalkanoates (PHA), consisting of
      medium-chain-length (MCL) hydroxyfatty acids (C5-C14), in recombinant Escherichia
      coli was investigated. E. coli mutants affected in fatty acid degradation and
      fatty acid de novo synthesis were employed. We established the functional
      expression of the Pseudomonas aeruginosa PHA synthase gene phaC1. The coding
      region of phaC1 was subcloned via PCR into vector pBluescript SK-. The resulting
      plasmid pBHR71 enabled functional expression of phaC1 under lac promoter control
      and conferred synthesis and accumulation of PHA to various strains of E. coli.
      PHA synthesis was analysed with respect to the carbon source in various E. coli
      fad and fab mutants. This study provided evidence that intermediates of the fatty
      acid beta-oxidation can be directed to PHA synthesis and that 3-hydroxydecanoyl
      CoA is the main substrate for PHA synthase PhaC1 from P. aeruginosa. The E. coli
      fadB mutant LS1298 containing plasmid pBHR71 and cultivated in LB medium
      containing 0.5% (w/v) decanoate revealed the strongest accumulation of PHA
      contributing to about 21% of the cellular dry weight, which was composed of 2.5
      mol% 3-hydroxyhexanoate, 20 mol% 3-hydroxyoctanoate, 72.5 mol% 3-hydroxydecanoate
      and 5 mol% 3-hydroxydodecanoate.

PMID- 9170276
TI  - Single-step polymerase chain reaction for combined gene detection and
      epidemiological typing in three bacterial models.
AB  - We describe a new polymerase chain reaction (PCR) for combined gene detection and
      epidemiological typing (COGEDET), which allows bacterial typing and gene
      detection in a one-step assay. This assay, in which target gene-specific primers
      are used under low-stringency annealing conditions, was evaluated on 32
      Staphylococcus aureus strains using toxic shock syndrome toxin 1 (tst) primers,
      30 Clostridium difficile strains using toxin A (toxA) primers, and 30 Escherichia
      coli strains using cytotoxic necrotizing factor (cnf) primers. Typing
      performances with COGEDET were compared to those of conventional random
      amplification polymorphic DNA (RAPD), and gene detection performances, to those
      of conventional PCR followed by Southern blot hybridization. Concordances between
      conventional PCR/Southern blot and COGEDET were 96.9, 100 and 96.7% for the
      detection of the tst, toxA and cnf genes, respectively. Discriminatory indexes
      for the conventional RAPD and COGEDET techniques were similar in the three
      bacterial species tested. These results show that the COGEDET assay can replace
      two separate assays for typing and genes detection respectively, thus saving both
      technicians' time and reagents.

PMID- 9170277
TI  - Characteristics of perceptual grouping in rats.
AB  - Parametric analysis was made of the characteristics by which proximity and
      alignment serve as cues for perceptual grouping in rats. Rats were initially
      conditioned to discriminate a series of horizontal lines from vertical lines.
      Following training, rats were presented with test stimuli that consisted of
      bistable arrays of disjunct dots. A grouping cue (greater proximity, greater
      alignment, or both) was randomly assigned to either the horizontal or vertical
      orientation. The effectiveness of the cues was based on behavioral responses to
      the cued orientation. Results indicated that proximity served as a cue for
      perceptual grouping. The effectiveness of the proximity cue was less for rats
      than found previously in humans and, unlike humans, diminished with increased
      stimulus scale. Rats did not respond to alignment cues when used in isolation,
      although alignment facilitated grouping when used in conjunction with proximity
      cues. Diminished effectiveness of grouping cues likely reduces object recognition
      abilities, particularly for complex visual stimuli.

PMID- 9170278
TI  - Differences in the sexual conditioned behavior of male and female Japanese quail
      (Coturnix japonica).
AB  - The conditioned responses of male and female Japanese quail (Coturnix japonica)
      were compared in a Pavlovian conditioning procedure in which presentation of a
      brief conditioned stimulus was immediately followed by the release of a
      copulation partner. Male quail vigorously approached the conditioned stimulus and
      were much more likely to enter the compartment housing their copulation partner
      than were female birds (Experiment 1). In females, sexual conditioning resulted
      in increased squatting (Experiment 2). This response was the reflection of sexual
      behavior rather than more general social behavior (Experiment 3). These findings
      provide the first definitive evidence of sexual learning in female quail and are
      consistent with the interpretation that sexual conditioning increases sexual
      arousal or receptivity in both sexes but the increase has different behavioral
      manifestations in male and female quail.

PMID- 9170279
TI  - Menstrual synchrony under optimal conditions: Bedouin families.
AB  - Ovarian cycles of females living and interacting together have been shown to
      synchronize in a number of species. In humans, the related phenomenon of
      menstrual synchrony has been reported among roommates and best friends. Menstrual
      data were collected prospectively for 3 months from 27 Bedouin nuclear families
      living under conditions optimally conducive for synchrony: (a) women living
      together for many years, (b) a highly sexually segregated society, (c) standard
      living conditions, and (d) minimal use of oral contraceptives. Results show
      unequivocally the existence of menstrual synchrony: A 20%-25% shift toward
      synchrony was found for sisters-roommates, sisters-roommates who are close
      friends, and the family (all women in the family between 13 and 50 years of age).

PMID- 9170280
TI  - Use of olfactory cues in foraging by owl monkeys (Aotus nancymai) and capuchin
      monkeys (Cebus apella).
AB  - The authors tested free-ranging New World monkeys (nocturnal owl monkeys [Aotus
      nancymai] and diurnal capuchin monkeys [Cebus apella]) to determine the extent to
      which they use olfactory cues to locate food hidden in containers at 2 of 6
      feeding sites within a 1 1/2-ha forested enclosure. These 2 sites were selected
      randomly for each trial and then were baited with banana and banana peel residue.
      The 4 other sites were unbaited and unscented. In trials in which the food was
      not visible to the monkeys, Aotus monkeys located the baited sites at a level
      greater than expected by chance, whereas Cebus monkeys did not. Use of olfactory
      information by Aotus monkeys in foraging may be an adaptation for nocturnal
      foraging because olfactory cues are more salient than visual cues at low light
      levels.

PMID- 9170281
TI  - Development of stone tool use by wild chimpanzees (Pan troglodytes).
AB  - At the age of 3.5 years, wild chimpanzees at Bossou, Guinea, begin to use hammer
      and anvil stones to crack oil-palm nuts to get the kernels. To clarify the
      developmental processes, the authors did a field experiment in which stones and
      oil-palm nuts were provided. Infant chimpanzees' stone-nut manipulation was
      observed and video recorded. Data were collected from 3 infants younger than 4
      years old from 1992 to 1995. The authors analyzed 692 episodes of infants' stone
      nut manipulation and 150 episodes of infants' observation of nut cracking
      performed by adults. Infants observed other chimpanzees' nut cracking and got the
      kernels from them. The stone-nut manipulation developed from a single action on a
      single object to multiple actions on multiple objects. Although infant
      chimpanzees at the age of 2.5 years already acquired basic actions necessary for
      nut cracking, they did not combine the actions in an appropriate sequence to
      perform actual nut cracking.

PMID- 9170282
TI  - Age differences in the response of California ground Squirrels (Spermophilus
      beecheyi) to avian and mammalian predators.
AB  - The antipredator behavior of juvenile and adult California ground squirrels
      (Spermophilus beecheyi) was videotaped in Experiment 1 to measure the effects of
      age on assessment of a briefly presented live dog and a model red-tailed hawk
      (Buteo jamaicensis) in simulated flight. Adult squirrels treated the hawk as more
      dangerous than the dog, whereas juvenile squirrels showed less differentiation of
      the predator types. Juvenile squirrels also perceived the dog as a more immediate
      danger than adult squirrels did. For Experiment 2, the red-tailed hawk model was
      compared with models of a nonthreatening turkey vulture (Cathartes aura) and crow
      (Corvus brachyrhynchos). Neither age class differentiated the avian models;
      however, the adult squirrels treated these birds as more threatening than the
      juvenile squirrels did. Both studies suggest that learning may contribute to
      predator assessment.

PMID- 9170283
TI  - Social referencing by young chimpanzees (Pan troglodytes).
AB  - Social referencing is the seeking of information from another individual and the
      use of that information to evaluate a situation. It is a well-documented ability
      in human infants but has not been studied experimentally in nonhuman primates.
      Seventeen young nursery-reared chimpanzees (14 to 41 months old) were observed in
      a standard social referencing paradigm in which they received happy and fear
      messages concerning novel objects from a familiar human caregiver. Each
      chimpanzee looked referentially at their caregiver, and the emotional messages
      that they received differentially influenced their gaze behavior and avoidance of
      the novel objects. It is concluded that chimpanzees can acquire information about
      their complex social and physical environments through social referencing and can
      use emotional information to alter their own behavior.

PMID- 9170284
TI  - Transfers of food from adults to infants in tufted capuchins (Cebus apella).
AB  - This study examined the behavioral mechanisms that support transfer of food from
      adults to infants in tufted capuchins (Cebus apella). Two captive groups of
      capuchins were presented with abundant quantities of unshelled pecans or
      commercial pellets. Five of 11 infant subjects could not open the nuts. A variety
      of tolerated interactions were initiated by infants toward adults, and food was
      frequently transferred. All such interactions were more frequent with nuts (a
      preferred food) than with pellets. Adult capuchins were equally tolerant of
      infant capuchins that could open nuts and those that could not. Tolerated
      interactions during feeding could result in acquisition of dietary information by
      young capuchins or to important, if intermittent, nutritional support.

PMID- 9170285
TI  - Developmental changes in manipulation in tufted capuchins (Cebus apella) from
      birth through 2 years and their relation to foraging and weaning.
AB  - This study examined the contributions of physical and sensorimotor development to
      manipulation in capuchins (Cebus apella) from birth to 2 years. Between months 1
      6 and 7-12, manipulation increased significantly in frequency, in the proportion
      that was vigorous or required fine motor control, and in the proportion directed
      at portable objects. Fine motor control, moving objects in relation to the body,
      and stamina are largely in place by 12 months, after which little changed. All
      elements of the manipulative repertoire have appeared, and vigorous and dexterous
      activities have peaked before fully independent foraging. Emergence of permanent
      dentition and achievement of approximately half of adult body size accompany the
      attainment of fully independent foraging at 15 months. Thereafter, increasing
      strength and specific knowledge probably contribute more to changing foraging
      competence in young capuchins than do stamina and sensorimotor development.

PMID- 9170286
TI  - Isolation and characterization of new anti-HIV and cytotoxic leads from plants,
      marine, and microbial organisms.
AB  - New cytotoxic isomalabaricane triterpenes have been isolated from a sponge
      Stelletta sp. (1-7); anti-HIV pterocarpans (8 and 9) and isoflavanoids (12-16 and
      18) were elucidated from two tropical plants in the genus Erythrina; and anti-HIV
      enniatins (20 and 22-23) were characterized from fungi in the genera Fusarium and
      Alternaria. The enniatins were evaluated for in vivo anti-HIV activity in the
      hollow fiber assay.

PMID- 9170287
TI  - Selective demethylation of some aconitine-type norditerpenoid alkaloids.
AB  - Demethylation of some aconitine-type norditerpenoid alkaloids was carried out
      with trimethylsilyl iodide and with HBr in glacial AcOH. Aconitine (10),
      cammaconine (23), delphinine (3), falconerine (18), lappaconitine (22), and
      talatizamine (24) afforded partially demethylated products. When methoxyl groups
      are present at the C-16 and C-18 positions, these are demethylated, and the
      methoxyl group at the C-1 position underwent demethylation in none the alkaloids
      studied except falconerine (18). With HBr-AcOH, in the case of alkaloids
      possessing a C-3 hydroxyl group, the methoxymethyl at C-18 formed a
      tetrahydrofuran, cyclizing at the C-6 position. Detailed NMR spectral studies
      (1H, 13C, 1H homonuclear COSY, HETCOR, and selective INEPT) carried out on the
      demethylation products have enabled accurate chemical shift assignments to be
      made for the demethylated alkaloids.

PMID- 9170288
TI  - Two new antiprotozoal 5-methylcoumarins from Vernonia brachycalyx.
AB  - Two new isomeric 5-methylcoumarins, 2'-epicycloisobrachycoumarinone epoxide (1)
      and cycloisobrachycoumarinone epoxide (2), have been isolated from the roots of
      Vernonia brachycalyx by means of bioactivity-guided fractionation. The structures
      were elucidated by MS and NMR spectroscopic methods. Compounds 1 and 2 showed in
      vitro activity against Leishmania major promastigotes and against Plasmodium
      falciparum schizonts and demonstrated an inhibition on the proliferation of human
      lymphocytes, which was significantly weaker than the antiparasitic effects.

PMID- 9170289
TI  - Structural investigation of resin glycosides from Ipomoea lonchophylla.
AB  - A fraction from Ipomoea lonchophylla, which was toxic to mice, contained an
      inseparable mixture of resin glycosides with differing numbers of C5 ester groups
      on the hexasaccharide chain. After alkaline hydrolysis of the esters, the
      structure of the major component (1) was elucidated using high-field NMR
      spectroscopy, mass spectrometry, chemical studies, and comparison with known
      resin glycosides. Compound 1 was identified as 3,11-dihydroxytetradecanoic acid
      11-O-beta-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->3)- [alpha
      rhamnopyranosyl- (1-->4)]-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->2)
      beta -fucopyranoside.

PMID- 9170290
TI  - Antifungal diterpenoid alkaloids from Delphinium denudatum.
AB  - The roots of Delphinium denudatum have yielded a new diterpenoid alkaloid, 8
      acetylheterophyllisine (1), in addition to the known alkaloids vilmorrianone (2),
      panicutine (3), denudatine (4), isotalatizidine (5), and condelphine (6), as well
      as 3-hydroxy-2-methyl-4H-pyran-4-one (7). Compounds 1, 3, and 7 have not been
      isolated from this plant previously. The structures of compounds 1, 3, and 7 were
      determined through spectral and X-ray diffraction analyses. Compounds 1-3 have
      shown antifungal activity against a number of human pathogenic fungi.

PMID- 9170291
TI  - A bioactive seco-rosane diterpenoid from Vellozia candida.
AB  - Bioassay-directed fractionation of the bioactive alcoholic extracts of Vellozia
      candida yielded a new 6,7-seco-rosane diterpenoid, candidalactone (1), which
      showed moderate toxicity toward DNA repair-deficient mutants of Saccharomyces
      cerevisiae. Another new but inactive rosane diterpenoid, candidenodiol (3), was
      also obtained.

PMID- 9170292
TI  - 3-Epi-aplykurodinone B, a new degraded sterol from Aplysia fasciata.
AB  - The anaspidean mollusk Aplysia fasciata from Rio San Pedro (Cadiz, Spain)
      contains the known degraded sterols aplykurodinone B (2) and aplykurodin B (4)
      together with the new 3-epi-aplykurodinone B (5). The structure of 5 was
      elucidated by interpretation of spectral data, and its relative stereochemistry
      was established using NOEDS experiments. The new compound 5 exhibited
      cytotoxicity against four tumor cell lines.

PMID- 9170293
TI  - Identification of the novel antimicrobial fatty acid (5Z,9Z)-14-methyl-5,9
      pentadecadienoic acid in Eunicea succinea.
AB  - The phospholipid fatty acid composition of Eunicea succinea was investigated, and
      the novel (5Z,9Z)-14-methyl-5,9-pentadecadienoic acid was identified. Structural
      characterization was accomplished by means of mass spectrometry of its
      pyrrolidide derivative, NMR, FT1R, and total synthesis. Other interesting
      phospholipid fatty acids in E. succinea were the tetracosapolyenoic acids
      6,9,12,15,18,21-tetracosahexaenoic acid (24:6) and 6,9,12,15,18
      tetracosapentaenoic acids (24:5). The title compound was particularly active
      against Gram-positive bacteria such as Staphylococcus aureus (MIC 0.24 mumol/mL)
      and Streptococcus faecalis (MIC 0.16 mumol/ mL).

PMID- 9170294
TI  - Two new nitrogenous sesquiterpenes from the sponge Axinyssa aplysinoides.
AB  - Bioassay-guided fractionation of the EtOAc extract of the Palauan sponge Axinyssa
      aplysinoides yielded two novel alkaloids, 1 and 2. The structure of 2
      (formylamino)trachyopsane (1) was determined by X-ray analysis; and the structure
      of N-phenethyl-N'-2-trachyopsanylurea (2), by interpretation of the spectral
      data.

PMID- 9170295
TI  - Sch 54445: a new polycyclic xanthone with highly potent antifungal activity
      produced by Actinoplanes sp.
AB  - A novel antifungal agent, Sch 54445, was isolated from the fermentation broth of
      an Actinoplanes species. Sch 54445 was identified as a polycyclic xanthone
      related to the albofungin family of compounds on the basis of analyses of
      spectroscopic data. As a broad-spectrum antifungal agent, Sch 54445 exhibits
      highly potent activities against various yeasts and dermatophytes with MIC values
      approximately 0.00038 microgram/mL.

PMID- 9170296
TI  - Bripiodionen, a new inhibitor of human cytomegalovirus protease from Streptomyces
      sp. WC76599.
AB  - Bripiodionen (1), a new natural product, was isolated from Streptomyces sp.
      WC76599 during the screening of microbial fermentation extracts for their ability
      to inhibit human cytomegalovirus protease. The structure of 1 was elucidated by
      spectroscopic methods. Compound 1 displayed inhibitory activity against human
      cytomegalovirus protease with an IC50 value of 30 microM.

PMID- 9170297
TI  - Isolation and structure elucidation of ardisenone: a new, cytotoxic alkenylphenol
      from Ardisia iwahigensis.
AB  - A methanol extract of leaves and twigs from Ardisia iwahigensis demonstrated
      toxicity toward brine shrimp as well as LNCaP, ZR-75-1, and Lu1 human cancer
      cells in culture. A novel alkenylphenol, (Z)-1,16-bis(3-hydroxy-5-methoxyphenyl)
      10-hexadecene-1,15-dione (ardisenone) (1), was isolated from the extract by
      bioassay-directed fractionation. This compound demonstrated moderate cytotoxicity
      against BC1, Lu1, Col2, KB, KB-V1, and LNCaP cell lines.

PMID- 9170298
TI  - Structural equation modeling: basic concepts and applications in personality
      assessment research.
AB  - Structural equation modeling (SEM) has become an increasingly used methodological
      strategy in psychology. Nevertheless, many psychologists continue to be unclear
      about how to apply this analytic tool in their research. This article reviews SEM
      from a conceptual perspective, particularly focusing on confirmatory factor
      analysis. Additionally, the relation between SEM and other analytic techniques
      (e.g., exploratory factor analysis) are addressed. A confirmatory factor analytic
      example is presented and reviewed in detail. Finally, limitations of SEM and
      other considerations are discussed.

PMID- 9170299
TI  - Development and factor analytic validation of the SPANAS among women in Spain:
      (more) cross-cultural convergence in the structure of mood.
AB  - We reported our findings on the development and preliminary validation of a
      Spanish-language measure of positive and negative affect. Using confirmatory
      factor analytic techniques on data generated by 708 women in northern Spain, we
      obtained reasonable construct validity and reliability data for the measure.
      Consistent with past cross-cultural studies, a two-factor Positive Affect
      Negative Affect (PA-NA)structure emerged, with PA and NA as relatively
      independent entities. The structure in this sample converged with that reported
      for a culturally separate group of participants. This factor structure has
      therefore revealed invariance across a number of cultural groups in Asia, Europe,
      and North America.

PMID- 9170300
TI  - Body image in adulthood: a projective approach.
AB  - A sample of 210 persons varying by age (young adults, middle-aged, older adults),
      gender, and relationship status (single or involved) were administered the
      Holtzman Inkblot Technique (HIT) and Geriatric Draw-A-Person (G-DAP) to ascertain
      projectively assessed aspects of body image in adulthood. Results suggested that
      both the HIT and G-DAP were sensitive to the effects of age and gender, wherein
      young adults scored higher on both HIT Barrier and Penetration than both middle
      aged or older adults. In addition, G-DAP scores favored young adults. HIT
      Penetration scores varied by both age and relationship status.

PMID- 9170301
TI  - Detecting feigned depression and schizophrenia on the MMPI-2.
AB  - Increasingly, investigations evaluating the effectiveness of the MMPI-2 in the
      assessment of malingering employ methodologies whereby research participants are
      asked to feigned specific disorders rather than just to "fake bad." Yet there is
      little research addressing the issue of whether different validity scales and
      indicators work differently in the detection of different feigned disorders. In
      this study the comparative effectiveness of a number of validity scales and
      indicators on the MMPI-2 to assess feigned depression and feigned schizophrenia
      were evaluated. Overall, the validity scales and indicators were better at
      detecting feigned schizophrenia than they were in detecting feigned depression,
      attributable, most likely, to closer familiarity with depressive experiences. The
      validity scales F, Fb, and F(p) best distinguish patients with schizophrenia from
      participants feigning schizophrenia, and F and Fb best distinguish patients with
      depression from participants feigning depression.

PMID- 9170302
TI  - Impact of rater knowledge on sexually abused and nonabused girls' scores on the
      Draw-A-Person: Screening Procedure for Emotional Disturbance (DAP:SPED).
AB  - Human figure drawings collected from a clinical sample of 20 sexually abused and
      20 nonsexually abused girls were randomly assigned to 1 of 2 case descriptions:
      Actual, in which raters were told the girls' actual abuse status, or Pretend, in
      which raters were told that drawings were made by girls with the opposite abuse
      status. Using the Draw-A-Person: Screening Procedure for Emotional Disturbance
      (DAP:SPED) scoring system developed by Naglieri, McNeish, and Bardos (1991),
      three raters independently scored 44 randomly ordered protocols, 4 of which were
      commonly rated as checks for rater accuracy and observer drift. Results revealed
      no significant effect for girls' abuse status or the case description given to
      raters, thereby suggesting that the DAP:SPED is sufficiently objective to
      withstand the confounding influence of varying case descriptions.

PMID- 9170303
TI  - Confirmatory factor analyses of the Anxiety and Depression content scales of the
      MMPI-2.
AB  - A sample of 408 patients with substance use disorders was equally divided into
      derivation and cross-validation samples. All patients had taken the MMPI-2.
      Exploratory factor analyses of MMPI-2 item data in the derivation sample
      permitted construction of latent variable measurement models for the Anxiety
      (ANX) and Depression (DEP) content scales. The 2-factor models for ANX consisted
      of Trait Anxiety and Worry, and the 3-factor model for DEP contained factors of
      Trait Depression, Hopelessness, and Self-Depreciation. Confirmatory factor
      analyses in cross-validation demonstrated a good fit for both models and for
      their combination in a 5-factor measurement model. Latent variable correlations
      in the 5-factor model helped explain the high correlation and low discriminant
      validity of ANX and DEP.

PMID- 9170304
TI  - A racial comparison of combat veterans evaluated for PTSD.
AB  - This study attempted to replicate the work of Frueh, Smith, and Libet (1996),
      which showed racial differences on psychological measures of dissociation/thought
      disturbance and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) F-K
      index in combat veterans evaluated for posttraumatic stress disorder (PTSD).
      Veterans completed the Beck Depression Inventory, Mississippi Scale for Combat
      Related PTSD, a fixed-response format version of the Dissociative Experiences
      Scale (DES-FRF), and MMPI-2 prior to treatment at a Veterans Affairs hospital
      outpatient PTSD clinic. Contrary to expectation, significant racial differences
      on the DES-FRF, MMPI-2 validity scales, and MMPI-2 Scales 6 and 8 were not found.
      Consistent with the previous study, no racial differences on measures of anxiety,
      depression, or PTSD symptomatology were found; nor were there racial differences
      on clinician ratings of global assessment of functioning or on most categories of
      psychiatric diagnoses. This suggests that Black and White combat veterans
      evaluated for PTSD do not differ with regard to reported manifestation or
      severity of psychopathology.

PMID- 9170305
TI  - Personality traits and psychiatric rehospitalization: a two-year follow-up.
AB  - This study followed 188 people with psychiatric impairments for 2 years after
      their discharge from a public psychiatric facility to assess the impact of
      personality traits on rehospitalization. A Cox regression analysis revealed a
      significant relation between the pattern of personality traits and psychiatric
      rehospitalization. The significant relation was retained after age, sex, race,
      education. Axis I diagnosis, subscale scores on the Brief Symptom Inventory,
      Methods of Coping Scale, Level of Expressed Emotion Scale, and scores on the
      alcohol and drug dependence scales of the MCMI-II were included in a stepwise
      inclusion analysis. The implications of these results for the assessment and
      treatment of people with psychiatric impairments are discussed.

PMID- 9170306
TI  - Fluorescence in biophysics: accomplishments and deficiencies.

PMID- 9170307
TI  - Design of profluorescent protease substrates guided by exciton theory.

PMID- 9170308
TI  - Picosecond fluorescence decay curves collected on millisecond time scale: direct
      measurement of hydrodynamic radii, local/global mobility, and intramolecular
      distances during protein-folding reactions.

PMID- 9170309
TI  - Time-resolved room temperature tryptophan phosphorescence in proteins.
AB  - The application of luminescence, primarily fluorescence, to the study of protein
      structure and dynamics has been extensively exploited to facilitate the
      understanding of complex biological problems. The interest in the application of
      phosphorescence, however, shows that new and complementary information can be had
      by careful optical studies of the phosphorescence lifetime. As in the early days
      of fluorescence spectroscopy in proteins, a complete and rigorous interpretation
      of the room temperature phosphorescence remains to be developed; nevertheless, it
      is clear that time-resolved phosphorescence yields new information on proteins in
      solution, for example, the detection of subtle conformational changes during
      protein folding, which is outside the sensitivity of earlier techniques. In
      addition, the great sensitivity of the phosphorescence lifetime to structural
      changes associated with rigidity and of nearby quenchers suggests that detailed
      structural information can be obtained when this approach is combined with the
      power of site-directed mutagenesis or other more biophysical techniques such as
      energy transfer to attached acceptors. We have presented basic aspects of time
      resolved room temperature phosphorescence spectroscopy and demonstrated some
      useful features of the spectroscopic signals as well as the general approach to
      data analysis. However, it should be understood that extensions of this approach
      will easily allow faster and improved time resolution with greater sensitivity to
      highly quenched phosphorescing states. In addition, many extensions of this
      approach that are common to fluorescence spectroscopy have yet to be developed.
      For example, combining time-resolved phosphorescence with anaerobic stopped-flow
      techniques and more rapid data acquisition electronics will enable studies of
      conformational dynamics with considerably shortened dead times. Other
      possibilities include extending the preliminary studies of in vivo-based
      spectroscopy, such as to microscopy. In conclusion, time-resolved phosphorescence
      presents a new dimension to biophysical methodologies for the study of proteins,
      and it is likely that this area will continue to grow in capability as the
      fundamental understanding improves.

PMID- 9170310
TI  - Fluorescence line narrowing spectroscopy: a tool for studying proteins.
AB  - Perhaps the most important contribution of FLN is that it provides an
      experimental approach to relate physical changes in the protein to predicted
      dynamical behavior. It is clear that the sample is inhomogeneously broadened in a
      continuous manner, consistent with the damped motion of proteins. At the same
      time configurational substates can be selected, suggesting that there is indeed a
      hierarchy of protein motion and structure. As yet, identification of the
      structure, and relating it to the spectra, has not been achieved. It is clear
      that the electric field exerted by neighboring atoms shifts the electronic
      transition, and the inhomogeneity is greater when the surrounding disorder is
      greater. The inhomogeneity for the chromophore in the protein is dependent on the
      protein conformation and is intermediate between that of a crystal and a glass.
      The phonon coupling also depends on the chromophore and the protein. Fluorescence
      line narrowing provides in addition ground- and excited-state vibrational
      frequencies, thereby allowing for structural differences between the excited
      state and the ground-state molecule to be detected.

PMID- 9170311
TI  - Determination of ground-state dissociation constant by fluorescence spectroscopy.

PMID- 9170312
TI  - 1La and 1Lb transitions of tryptophan: applications of theory and experimental
      observations to fluorescence of proteins.

PMID- 9170313
TI  - Enhancement of protein spectra with tryptophan analogs: fluorescence spectroscopy
      of protein-protein and protein-nucleic acid interactions.

PMID- 9170314
TI  - Time-resolved fluorescence of constrained tryptophan derivatives: implications
      for protein fluorescence.

PMID- 9170315
TI  - Conformational heterogeneity in crystalline proteins: time-resolved fluorescence
      studies.

PMID- 9170316
TI  - Fluorescence methods for studying equilibrium macromolecule-ligand interactions.

PMID- 9170317
TI  - Fluorescence methods for studying kinetics of protein-folding reactions.

PMID- 9170319
TI  - Long-lifetime metal-ligand complexes as probes in biophysics and clinical
      chemistry.

PMID- 9170318
TI  - Intramolecular pyrene excimer fluorescence: a probe of proximity and protein
      conformational change.

PMID- 9170320
TI  - N-terminal modification of proteins for fluorescence measurements.

PMID- 9170322
TI  - Fluorescence assays for DNA cleavage.

PMID- 9170321
TI  - Fluorescence studies of zinc finger peptides and proteins.

PMID- 9170323
TI  - Fluorescent nucleotide analogs: synthesis and applications.

PMID- 9170324
TI  - Fluorescence approaches to study of protein-nucleic acid complexation.

PMID- 9170325
TI  - Fluorescence resonance energy transfer as a probe of DNA structure and function.

PMID- 9170326
TI  - Energy transfer methods for detecting molecular clusters on cell surfaces.

PMID- 9170327
TI  - Distribution analysis of depth-dependent fluorescence quenching in membranes: a
      practical guide.

PMID- 9170328
TI  - Mechanism of leakage of contents of membrane vesicles determined by fluorescence
      requenching.

PMID- 9170329
TI  - Fluorescence probes for studying membrane heterogeneity.

PMID- 9170330
TI  - Preparation of bifluorescent-labeled glycopeptides for glycoamidase assay.

PMID- 9170331
TI  - Preparation of fluorescence-labeled neoglycolipids for ceramide glycanase assays.

PMID- 9170332
TI  - Applications of fluorescence resonance energy transfer to structure and mechanism
      of chloroplast ATP synthase.

PMID- 9170333
TI  - Intrinsic fluorescence of hemoglobins and myoglobins.

PMID- 9170334
TI  - Multiple-domain fluorescence lifetime data analysis.

PMID- 9170335
TI  - Neuropeptides and mast cells.

PMID- 9170336
TI  - Naratriptan: biological profile in animal models relevant to migraine.
AB  - The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H
      indole-5-ethane-sulphonamide), a novel 5HT1B/1D receptor agonist, was
      investigated in a variety of experimental models of relevance to migraine.
      Naratriptan has high affinity for human recombinant 5HT1B and 5HT1D receptors
      (pKi = 8.7 +/- 0.03 and 8.3 +/- 0.1, respectively) and causes contractions of dog
      isolated basilar and middle cerebral artery (EC50 values of 0.11 and 0.07 microM,
      respectively). Naratriptan causes small contractions of human isolated coronary
      arteries (EC50 value of 0.17 microM; maximum contraction equivalent to 33% of 5HT
      maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of
      the carotid arterial bed (CD50 dose = 19 +/- 3 micrograms kg-1) and, in
      anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein
      extravasation in the dura (ID50 = 4.1 micrograms kg-1). In a variety of
      antinociceptive tests, naratriptan has no effect even at high doses. In conscious
      rats and dogs, naratriptan has high oral bioavailability (71% and 95%,
      respectively). The data show that naratriptan is a selective agonist at 5HT1B/1D
      receptors, with a pharmacological profile very similar to that of sumatriptan,
      albeit 2-3 fold more potent. These observations, coupled with high oral
      bioavailability in animals, suggest that naratriptan has the profile of an orally
      effective anti-migraine drug.

PMID- 9170337
TI  - Direct evidence for central sites of action of zolmitriptan (311C90): an
      autoradiographic study in cat.
AB  - The trigeminovascular system consists of bipolar neurons which innervate pain
      sensitive intracranial structures and projecting to neurons in the superficial
      laminae of the caudal trigeminal nucleus and of the dorsal horns of C1 and C2.
      The serotonin (5HT1B/D) agonist zolmitriptan (311C90) has been shown to be
      effective in the treatment of acute attacks of migraine and experimental data
      suggest that it may have both peripheral and central sites of action. This study
      sought to further investigate possible central effects of zolmitriptan (311C90)
      by examining its distribution in the central nervous system. Specific binding of
      [3H]-zolmitriptan was determined both ex vivo and in vitro in the cat brain. For
      the ex vivo studies, cats were anaesthetized with halothane and alpha-chloralose
      (60 mg/kg intraperitoneal). A femoral vein catheter was inserted for injection of
      the [3H]-zolmitriptan and then 1 h after injection the brain removed. For the in
      vitro studies fresh frozen brain slices were incubated with labelled and masking
      concentrations of zolmitriptan. The distribution of [3H]-zolmitriptan was
      determined using quantitative autoradiographic methods. The in vitro work
      demonstrated specific binding of [3H]-zolmitriptan in the superficial laminae of
      the trigeminal nucleus caudalis and dorsal horns of the C1 and C2 cervical spinal
      cord. The density of binding was 53 +/- 9 fmol/mg for the trigeminal nucleus
      caudalis, 47 +/- 7 fmol/mg for C1 and 50 +/- 6 fmol/mg for C2. The ex vivo work
      demonstrated binding in anatomically identical areas which was less dense than
      that seen with the in vitro method. These data confirm the existence of a
      population of receptors that specifically bind zolmitriptan following systemic
      administration. These receptors may, in part, be responsible for its clinical
      efficacy and reinforce the importance of central trigeminal neurons as a possible
      site of action of anti-migraine drugs.

PMID- 9170338
TI  - Enhanced nitric oxide release during cortical spreading depression following
      infusion of glyceryl trinitrate in the anaesthetized cat.
AB  - Intravenous infusion of glyceryl trinitrate (GTN) into migraineurs induces an
      immediate headache followed by migraine. We studied the effect of GTN (0.25
      microgram kg-1 min-1) on local cerebrovascular laser Doppler flux (rCBFLDF),
      artery diameter and NO concentration (selective NO microelectrode) in the pial
      middle cerebral artery perfusion territory of the anaesthetized cat, at rest and
      during cortical spreading depression (SD). GTN infusion induced a significant
      increase in pial artery diameter, rCBFLDF, and NO concentration. Following
      termination of infusion, NO concentrations remained significantly elevated above
      controls for 60 min, other parameters returned to baseline within 10 min (p <
      0.05, ANOVA, post hoc Dunnett's multiple comparison procedure). Two hours after
      termination of infusion KCl-evoked SD was initiated. GTN-treated animals
      exhibited significantly (p < 0.05, Kruskal-Wallis) elevated SD-induced NO release
      compared to controls. All other parameters remained unaffected. Our results
      demonstrate that GTN induces a prolonged increase in local NO concentrations and
      enhances SD-induced NO release.

PMID- 9170339
TI  - Release of histamine from dural mast cells by substance P and calcitonin gene
      related peptide.
AB  - The aim of the present study was to examine if the neuropeptides substance P
      (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive
      intestinal peptide (VIP) can stimulate histamine release from mast cells in the
      dura mater and thereby play a role in cranial vasoregulation and local neurogenic
      inflammation. Dura mater mast cells were compared with peritoneal mast cells in
      the rat. Histamine was released from dura mater mast cells by compound 48/80, SP
      and CGRP but from peritoneal mast cells only by compound 48/80 and SP. NPY and
      VIP released quite small amounts of histamine from dural mast cells. The release
      of SP and CGRP from rat dura mater mast cells was blocked by the receptor
      antagonists FK888 and CGRP8-37 respectively, suggesting receptor mediated release
      mechanisms. None of the stimuli released histamine from human or porcine dural
      mast cells, possibly because the sampling procedure injures and incapacitates the
      cells.

PMID- 9170340
TI  - Nitric oxide synthase inhibition in the histamine headache model.
AB  - Histamine has been widely used experimentally to induce headache in healthy
      subjects and migraine in migraineurs. There is evidence that the vascular effects
      of histamine are at least partially mediated by nitric oxide (NO). Hence we
      hypothesized that subjective symptoms and hemodynamic effects of histamine could
      be reduced by systemic NO-synthase inhibition. We therefore studied the effect of
      pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO
      synthase, or placebo on headache, flush and discomfort scores during histamine
      infusion. Additionally, blood flow velocities in the middle cerebral and the
      ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA
      blunted the effect of histamine in the ophthalmic artery and the ocular
      circulation, NO-synthase inhibition did not mitigate subjective symptoms.
      Histamine did not affect mean blood flow velocities in the middle cerebral
      artery. Hence, we conclude that NO-synthase inhibition reduces the histamine
      induced vascular effects in the ocular circulation, but is not sufficient to
      attenuate or abort the subjective symptoms provoked by histamine infusion.

PMID- 9170341
TI  - Haemodynamic correlates of early and delayed responses to sublingual
      administration of isosorbide dinitrate in migraine patients: a transcranial
      Doppler study.
AB  - In normal subjects or migraine patients, nitrates induce a non-specific early
      headache caused by vasodilation of intracranial arteries. In migraineurs a
      delayed headache response to nitrates may have a typical clinical profile of a
      spontaneous migraine attack. The cerebral vasomotor changes of this delayed
      response require further study. Isosorbide dinitrate (IDN), an exogenous nitric
      oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral
      transcranial Doppler device was used to monitor bilateral mean velocity (Vm)
      changes at the middle cerebral artery (MCA) after IDN administration and until
      delayed headache occurred. Spontaneous migraine-like headache occurred only in
      migraine patients during the delayed phase after IDN and was accompanied by a
      prolonged arterial vasodilation compared to normal subjects. This vasomotor
      response was more evident on the customary side of the head pain of a spontaneous
      migraine attack. Our findings suggest a particular vasomotor response to nitrates
      in migraine patients. This response is associated with the nitrate-induced
      headache and it is not evident in healthy pain-free controls during the delayed
      phase after administration of an NO donor. Owing to the short half-life of NO,
      the neurotransmitter released by IDN, and because of the late onset of headache,
      we believe the mechanism is unlikely to be vascular in origin, but may have a
      neurogenic component.

PMID- 9170342
TI  - Influence of caffeine and caffeine withdrawal on headache and cerebral blood flow
      velocities.
AB  - Caffeine consumption may cause headache, particularly migraine. Its withdrawal
      also produces headaches and may be related to weekend migraine attacks.
      Transcranial Doppler sonography (TCD) has shown changes in cerebral blood flow
      velocities (BFV) during and between attacks of migraine. In order to examine
      whether headache and changes in BFV could develop from controlled caffeine
      alterations, 20 healthy volunteers without a headache history, underwent clinical
      evaluation, TCD and serum caffeine measurements on four occasions, comparing
      conditions of regular caffeine intake, caffeine withdrawal and "re-caffeination".
      After 24 h of complete caffeine abstinence, 10 suffered from moderate to severe
      headaches with complete recovery within 1 h after caffeine intake. The BFVs in
      both middle cerebral, both posterior cerebral and basilar arteries were higher
      following the withdrawal period, reaching statistical significance in the left
      middle cerebral basilar and both posterior cerebral arteries. BFVs decreased
      significantly within half an hour after caffeine intake in all subjects, and were
      similar to baseline values after 2 h. Our results emphasize the relationship
      between caffeine withdrawal, the development of headache and alterations in
      cerebral blood flow velocities. Also, these findings indicate that accurate
      interpretation of TCD measurements should account for the influence of caffeine
      on BFVs.

PMID- 9170343
TI  - Cerebrovascular reactivity in migraine during headache-free intervals.
AB  - Alterations of intracranial vessel tone have been implicated in the
      pathophysiology of migraine. The cerebrovascular reactivity was measured by means
      of transcranial Doppler in 60 migraine patients with (n = 30) or without aura (n
      = 30) during the headache-free interval and in 30 healthy controls. The vasomotor
      response was evaluated during hypercapnia induced by inhalation of a mixture of
      CO2 5% and O2 95% and during hypocapnia obtained after voluntary
      hyperventilation. To improve the power of the study in detecting possible
      abnormalities of cerebrovascular reactivity, two different measures were
      performed at 1 week intervals in migraine patients and controls. Reactivity index
      values during CO2 inhalation were significantly different (p = 0.01) among the
      three groups during the first and second measurements; in particular, lower
      values were found in patients suffering from migraine without aura with respect
      to controls (p < 0.05, Scheffe's test). Values of reactivity index obtained
      following induction of hypocapnia did not differ between migraine patients and
      controls (all p values > 0.05). Our data suggest a reduced vasodilatory response
      to hypercapnia of cerebral arterioles in patients suffering from migraine without
      aura with respect to controls that might be related to baseline arteriolar
      vasodilation.

PMID- 9170344
TI  - Anginal headache and its basis.
AB  - A case is presented of angina manifesting itself initially solely as vertex and
      occipital headache, accompanied by EKG changes, provoked by exercise and relieved
      by rest. It was totally relieved by coronary bypass surgery and, later, by
      angioplasty. Its mechanism is probably a variation on the neural convergence
      usually invoked to explain the more typical chest pain angina.

PMID- 9170345
TI  - Electrophysiological effects of Bacillus sphaericus binary toxin on cultured
      mosquito cells.
AB  - The electrophysiological effects of both trypsinactivated native and 42- and 51
      kDa cloned binary toxins of Bacillus sphaericus were investigated on cultured
      Culex quinquefasciatus cells using the patchclamp technique. Rates of reduction
      in whole-cell membrane resistance were correlated with increasing native toxin
      concentration. The 42- or 51-kDa cloned toxin alone at 50 micrograms/ml reduced
      the resistance. Electrophysiological effects occurred before any changes were
      visible by phase-contrast microscopy.

PMID- 9170346
TI  - Pathogenicity of axenic Steinernema feltiae, Xenorhabdus bovienii, and the bacto
      helminthic complex to larvae of Tipula oleracea (Diptera) and Galleria mellonella
      (Lepidoptera).
AB  - The pathogenicity of the nematode-bacterium complex Steinernema feltiae
      Xenorhabdus bovienii to larvae of Tipula oleracea and Galleria mellonella was
      investigated by injection of dauer juvenile nematodes carrying their bacterial
      symbiont cells (monoxenic nematodes). Axenic nematodes (free of bacteria) and the
      symbiotic bacteria themselves were tested. The LC50 of X. bovienii in T. oleracea
      was 15,700 colony forming units (CFU)/larva compared to < or = 8 CFU in G.
      mellonella. Xenorhabdus bovienii is apparently removed from the tipulids
      hemolymph, possibly by cellular defense mechanisms. Axenic nematodes were less
      pathogenic than monoxenic nematodes for both insects. The difference was less
      pronounced in G. mellonella larvae: one axenic nematode was sufficient to kill
      80% in 1 day. The remaining insects found dead after 50 days were developmentally
      arrested. In T. oleracea 20 axenic nematodes caused 39% whereas 20 monoxenic
      dauer juveniles caused 90% mortality within 8 days. The data indicate that the
      virulence of the S. feltiae/X. bovienii complex is greater than the additive
      effect of the nematodes and their bacteria, further evidence for the synergistic
      activity of the symbiotic bacto-helminthic complex during pathogenesis.

PMID- 9170347
TI  - Encapsulation of the entomopathogenic nematode Steinernema feltiae in Tipula
      oleracea.
AB  - The encapsulation response of Tipula oleracea to the entomopathogenic nematode
      Steinernema feltiae was investigated by exposing the insects to nematode dauer
      juveniles (DJs) and by injecting DJs with and without the symbiotic bacteria
      Xenorhabdus bovienii. The encapsulation response varied considerably between
      individual insect larvae. The variation could not be attributed to a more or less
      scattered nematode invasion over time since it was also recorded after
      simultaneous injection of a fixed DJ dose. The proportion of encapsulated
      nematodes declined with increasing dose (injected DJs/larva) from approx 80% for
      1 DJ/larva to 33-34% for 20 DJ/larva. Tipula oleracea larvae were capable of
      encapsulating nematodes with and without symbionts inside the hemocoel; however,
      at doses of 10 and 20 DJ/larva, axenic nematodes were encapsulated less
      frequently than monoxenic nematodes. Injected axenic nematodes that were not
      encapsulated did not develop in T. oleracea larvae but disappeared from the
      insect's hemocoel. Coinjection of symbiotic bacteria increased encapsulation of
      axenic nematodes, showing that X. bovienii is triggering the encapsulation
      response of T. oleracea against S. feltiae.

PMID- 9170348
TI  - Phylogenetic relationships of entomopathogenic nematodes (Heterorhabditidae and
      Steinernematidae) inferred from partial 18S rRNA gene sequences.
AB  - Aligned 265-bp sequences of partial 18S rRNA gene were used to infer phylogenetic
      relationships among entomopathogenic nematodes by using maximum parsimony and
      likelihood methods. Phylogenetic analyses support Heterorhabditidae and
      Steinernematidae belonging to different monophylies. There was more sequence
      divergence in Steinernema species than in Heterorhabditis species. These results
      are congruent with the phylogenies based on morphological, life cycle, and
      distributional evidence. Examination of all trees within 1% of the length of the
      most parsimonious trees and bootstrap analyses support most relationships among
      Steinernema species but the relationships among Heterorhabditis species were not
      supported. We suggest that the partial 18S rRNA gene sequences may be too
      conserved for phylogenetic inference among Heterorhabditis species, but are well
      suited for phylogenetic inference within and among closely related families and
      genera of entomopathogenic nematodes and for inferring phylogenetic relationships
      among Steinernema species.

PMID- 9170349
TI  - Detection of phenoloxidase activity in the hemolymph of tsetse flies, refractory
      and susceptible to infection with Trypanosoma brucei rhodesiense.

PMID- 9170350
TI  - Society for Epidemiologic Research 30th annual meeting. Edmonton, Alberta,
      Canada, June 12-14, 1997. Abstracts.

PMID- 9170351
TI  - European Society of Anaesthesiologists annual congress. Lausanne, 3-6 May 1997.
      Abstracts.

PMID- 9170352
TI  - Radiology 1997. Imaging, Science and Oncology. Birmingham, United Kingdom, 19-21
      May 1997. Abstracts.

PMID- 9170353
TI  - Association of Surgeons of Great Britain and Ireland annual meeting. 9-11 April
      1997. Abstracts.

PMID- 9170354
TI  - The British Society of Gastroenterology Diamond Jubilee. March 1997.

PMID- 9170355
TI  - 44th Annual meeting of the Society of Nuclear Medicine. San Antonio, Texas, June
      1-5, 1997. Abstracts.

PMID- 9170356
TI  - Fractures of the femoral diaphysis in children. 1976.

PMID- 9170357
TI  - Accuracy of leg length prediction in children younger than 10 years of age.
AB  - In this study, the authors attempted to predict the ultimate leg length in normal
      children with normally growing legs, using Green-Anderson and Moseley techniques
      with chronologic and skeletal age. The predictions were based on serial growth
      studies of children between 5 and 10 years of age. Using skeletal age for
      prediction, the absolute mean error in predicting the ultimate leg length was 2.4
      cm using the Green-Anderson method and 2.58 cm using the Moseley method. Using
      the Moseley method for length prediction in boys, the mean error was 3.8 cm using
      skeletal age and 1.5 cm using chronologic age. For girls, using the Moseley
      method of leg length prediction, the mean error was 1.55 cm with skeletal age and
      2.46 cm with chronologic age. The significance of this study is that skeletal
      age, as determined by the Gruelich and Pyle Atlas, does not improve the accuracy
      of prediction of ultimate leg length in children younger than 10 years of age,
      except in girls with advanced bone age.

PMID- 9170358
TI  - Congenital clubfoot. Month of conception.
AB  - The medical records of 330 children who were born with uncomplicated congenital
      clubfoot were reviewed retrospectively. To determine their months of conception,
      the duration of gestation was extrapolated and those which were less than 40
      weeks were noted. The years of conception for the studied children were from 1956
      to 1994. Months of the year were ascribed angle values and the distribution of
      conceptions per month were grouped in radial manner. Using a circular analysis
      for variance a lack of uniform circular distribution was found for the grouped
      months of conception. There is a significant seasonal variation in the data. The
      mean month of conception was June. This finding is at variance with the peak
      months of conception for the population of the United States for the years 1989
      through 1993. The theory that congenital clubfoot is caused by an intrauterine
      Enterovirus may be supported by this data. The summer and fall peak of
      Enterovirus infections in temperate climates coincide with the stage of
      embryologic development (> 8 weeks) which would allow an anterior horn cell
      lesion to lead to a deformity such as congenital club foot.

PMID- 9170359
TI  - Surgery of the spine in myelodysplasia. An overview.
AB  - Significant spinal deformity is particularly common in nonambulatory patients
      with myelodysplasia. Progressive deformity may be caused by congenital anomalies,
      paralytic collapse, hip contractures, or spinal cord tethering. Existing or
      projected functional impairment should be the principle indication for treatment.
      Surgical treatment is complicated by poor soft tissue coverage, associated
      contractures, lack of sensation, weak bone, and absence of posterior elements.
      Successful fusion can be achieved by circumferential (anterior and posterior)
      fusion and current rigid segmental instrumentation. The unique deformities and
      bony anatomy require individualized techniques to achieve fixation.

PMID- 9170360
TI  - Osteochondritis dissecans as a cause of developmental dislocation of the radial
      head.
AB  - Osteochondritis dissecans of the capitellum produces an area of focal necrosis
      that may result in a potentially unstable relationship between the capitellum and
      the radial head. Seven patients with developmental instability of the radial head
      secondary to osteochondritis dissecans of the capitellum treated between 1984 and
      1995 were studied. All patients were male with an average age of 13 years. The
      most common symptom was pain with a decrease in range of motion. Patients lacked
      an average of 24.3 degrees extension. Initial plain radiographs were most helpful
      for evaluating the relationship of the radial head to the capitellum, and
      tomography or magnetic resonance imaging were helpful for the detection of loose
      bodies. The most common direction for instability was posterolateral. Treatment
      varied from conservative management with nonsteroidal antiinflammatory medication
      to open reduction and internal fixation of an osteochondral fragment. The average
      followup was 3.2 years. At latest followup, 11 patients were pain free; however,
      they lacked an average of 17 degrees extension. Only 2 patients progressed to
      complete dislocation of the radial head. Developmental instability of the radial
      head may occur secondary to osteochondritis dissecans of the capitellum. Plain
      radiographs are sufficient for initial detection and followup. Treatment is
      determined by the presence of loose bodies and the characteristics of the
      osteochondral defect. Initial symptoms will resolve; however, lack of extension
      may persist.

PMID- 9170361
TI  - The cerebral palsied hip.
AB  - Controversy exists regarding the role of pelvic obliquity in hip dysplasia and
      cerebral palsy. Earlier authors noted such a relationship but did not confirm its
      existence by scientific study. The current study confirms the association of
      pelvic obliquity to hip dysplasia in spastic cerebral palsy. At presentation of
      subluxation or dislocation before surgery, 80 patients were indexed into 5 body
      alignment types. Reclassifications were performed with passage of time to study
      the natural history and effects of surgery. Hip dysplasia was found in all cases
      to be consistent with the forces related to pelvic obliquity.

PMID- 9170362
TI  - Proposed curriculum model for resident education in pediatric orthopaedic
      surgery.
AB  - A curriculum developed for pediatric orthopaedic residency training is described.
      The curriculum is practice based, emphasizing those components thought to be
      necessary for orthopaedic practice. Highly technical or esoteric topics are
      deemphasized, because they are not relevant to practice capabilities at the end
      of residency training. The curriculum is designed to serve as a guide for
      educational direction in pediatric orthopaedic residency training, and not as a
      description of competency. Resource materials are being developed to provide the
      educator with relevant clinical material, objectives, and bibliography. The
      advantages of a practice based curriculum warrant further development of this
      model for other orthopaedic subspecialties.

PMID- 9170363
TI  - Current trends in the treatment of femoral shaft fractures in children and
      adolescents.
AB  - Healthcare cost containment and a desire for early discharge of the pediatric
      patient to the home environment have become important factors in the treatment of
      femoral shaft fractures in children. As a result, newer techniques of treatment
      have become popular. The immediate hip spica cast remains the primary method of
      treatment for most children 6 years of age and younger. The treatment for
      children between the ages of 6 and 10 years is the most controversial. Many such
      patients may be treated successfully with immediate hip spica casts. However,
      external fixation and flexible intramedullary rod fixation are being used more
      frequently, particularly in patients with multiple trauma. The initial enthusiasm
      for rigid intramedullary rod fixation of adolescent femoral fractures has been
      tempered by recent reports of femoral head avascular necrosis. Avoiding the
      piriformis fossa during rod insertion may prevent this complication. Most
      children and adolescents with femoral fractures can be treated successfully with
      a brief hospital course without compromising care or outcome.

PMID- 9170365
TI  - Traction in developmental dislocation of the hip. Is its use justified?
AB  - Traction has been used for decades in the treatment of developmental dislocation
      of the hip. Traction is advocated to facilitate closed reduction and to decrease
      the need for open reduction. The use of prereduction traction also is advocated
      to decrease the incidence of proximal femoral growth disturbance (aseptic
      necrosis). Recently, several studies have called into question this widely
      accepted adjunct in the treatment of developmental dislocation of the hip. A
      critical look was taken at the use of traction in the treatment of developmental
      dislocation of the hip and whether its use can be justified by the existing
      medical literature was ascertained. Although there are several impressive reports
      of the positive effects of traction in developmental dislocation of the hip,
      there are no clinical or experimental studies on the direct effect of traction.
      There are also no well controlled studies to analyze the effect of traction as a
      single variable. Thus, it cannot be proven that traction alters the outcome of
      developmental dislocation of the hip treatment, and hence, there is only
      anecdotal basis for its use in the treatment of developmental dislocation of the
      hip.

PMID- 9170364
TI  - Shortening in femoral shaft fractures in children treated with spica cast.
AB  - Early spica cast treatment is one method used for children's femoral shaft
      fractures; it is increasingly advocated as treatment that allows early hospital
      discharge. The outcome of early spica cast treatment in 100 children, ages 2 to
      10 years, with uncomplicated and isolated closed femoral shaft fractures treated
      at Johns Hopkins Hospital between October 1987 and March 1994 were analyzed. The
      objective was to identify those children who can be treated safely and dependably
      with early spica casting without excessive shortening of the fracture fragments.
      Eighty-one (81%) children had an acceptable outcome and 19 (19%) had an
      unacceptable outcome by the definition of more than 25 mm of fracture fragment
      overlap after clinical healing. A new clinical test, the telescope test, was
      statistically significant for correlation with spica cast outcome. Age, gender,
      fracture, location, mechanism of injury, fracture type, and resting radiograph of
      fracture fragment overlap were not statistically significant. The telescope test
      had a sensitivity of 80% and a specificity of 85% for predicting outcome. The
      relative risk for failure of spica cast treatment with a positive telescope test
      was 20.4 (95% confidence limits = 2.7-225.1). Children 2 to 10 years of age with
      uncomplicated femoral shaft fractures and a negative telescope test can be
      treated appropriately in most cases with early application of a spica cast.

PMID- 9170366
TI  - Occlusion of the left iliac artery after retroperitoneal exposure of the spine.
AB  - This case report describes a rare but treatable complication of anterior lumbar
      surgery. The patient underwent a revision anterior fusion from L2 to S1. Complete
      thrombotic occlusion of the left iliac artery developed in the patient. Prompt
      recognition of vascular compromise and arterial bypass of the iliac system lead
      to excellent functional recovery.

PMID- 9170367
TI  - Myelopathy due to hypoplasia of the atlas. A case report.
AB  - The authors report a 73-year-old woman who had spinal cord compression develop
      because of hypoplasia of the atlas associated with a retroodontoid pseudotumor
      diagnosed by magnetic resonance imaging. Radiographs of the cervical spine showed
      narrowing of the spinal canal at the level of the atlas and severe osteoarthrosis
      of the atlantoaxial joint without atlantoaxial subluxation. A remarkable
      neurologic recovery followed decompressive laminectomy of the atlas with
      posterior occipitocervical fusion. Postoperative magnetic resonance imaging
      showed significant reduction of the retroodontoid pseudotumor by fusion alone.
      The magnetic resonance imaging finding of spontaneous reduction of retroodontoid
      pseudotumor after posterior fusion argues against a need for transoral removal,
      which has a significant complication rate.

PMID- 9170368
TI  - Total hip arthroplasty in patients with osteonecrosis. The effect of cement
      techniques.
AB  - One hundred fifteen patients who underwent total hip replacement for
      osteonecrosis between June 1972 and April 1990 were divided into 3 groups
      according to the cause of the disorder: (1) osteonecrosis secondary to alcoholism
      (21 patients), (2) osteonecrosis secondary to hypersteroidism (29 patients), and
      (3) idiopathic osteonecrosis (65 patients). To determine the differences in short
      and long term arthroplasty failure rates, these 3 patient groups were compared
      with a group of 202 patients who received total hip replacement for
      osteoarthritis. Statistical analyses were carried out on the following
      definitions of failure: loosening of the acetabular component, loosening of the
      femoral component, and revision arthroplasty. Radiolucency and postoperative pain
      scores also were evaluated. A significant difference in the rate of failure
      because of loosening of the femoral component was found among the 4 groups.
      Likewise, a significant difference was found among the 4 groups in all revisions
      or loosenings or both. However, only the comparison between the idiopathic
      osteonecrosis and osteoarthritic groups showed a significant difference with
      survival analysis. Second generation cement technique was as significant as any
      variable relating to failure. The authors conclude that total hip arthroplasty is
      an equally viable treatment for the 3 types of osteonecrosis examined in this
      study; however, failure might be more imminent in studies where larger numbers
      are needed.

PMID- 9170369
TI  - Massive osteolysis after ceramic on ceramic total hip arthroplasty. A case
      report.
AB  - The case of a 66-year-old woman who sustained a pathologic femur fracture
      secondary to extensive osteolysis distal to a pressfit femoral prosthesis with a
      ceramic on ceramic bearing surface is reported. The femoral and acetabular
      bearing surfaces showed signs of visible wear, although the stem showed little
      evidence of burnishing. Material curetted from the femoral medullary canal in the
      area of the osteolysis contained extensive amounts of histiocytes and foreign
      body debris. Qualitative spectrographic analysis of the curetted material showed
      levels of aluminum to be approximately 10 times more prevalent than either cobalt
      or chromium. Although there is little understanding of the cellular reactions to
      ceramic debris products, the extensive osteolysis seen in this patient suggests
      that alumina ceramic bearings may not be as biologically inert as initially
      perceived.

PMID- 9170370
TI  - False aneurysm of the common femoral artery after total hip arthroplasty. A case
      report.
AB  - A 59-year-old healthy man presented with osteoarthritis of his left hip that was
      recalcitrant to nonoperative treatment. He subsequently elected to have
      arthroplasty of the hip performed. At 3 months after arthroplasty, he returned
      reporting progressive groin pain: most remarkable was a palpable mass in the
      groin region. An arteriogram showed a radiodense mass adjacent to the acetabulum,
      and a computed tomography scan with contrast confirmed a large false aneurysm
      originating from the common femoral artery. In this particular case, a pointed
      Hohmann retractor punctured the common femoral artery, creating the dynamics of
      the development of a false aneurysm. Primary suture repair of the vascular defect
      was performed, followed by a complete and uncomplicated recovery of the patient
      to full activity. Since this case, the authors have discontinued the use of
      pointed. Hohmann retractors and now use a blunt, rounded Hohmann retractor during
      total hip arthroplasty without compromising acetabular exposure. However, care
      must be taken in blunt retractor placement to avoid retractor slippage during the
      procedure. This case shows the need for awareness of potential mechanisms for
      vascular injury related to total hip arthroplasty.

PMID- 9170371
TI  - Analysis of particles in acetabular components from patients with osteolysis.
AB  - Acetabular polyethylene components were quantitatively analyzed for the presence
      of third body particles from 38 consecutively retrieved components. Backscattered
      electron imaging and correlated energy dispersive x-ray analysis were used for
      the assessments. Retrievals were divided into 4 groups based on methods of
      fixation and metal alloy types: 8 hydroxyapatite coated, 6 cobalt chrome porous
      coated, 17 titanium porous coated, and 7 cemented implants were evaluated. The
      backscattered electron imaging data showed that the components from the
      hydroxyapatite coated implants had larger particles than did the components from
      the cemented group. The hydroxyapatite group had 51 +/- 52 particles per mm2. The
      cobalt chrome alloy group had 10 +/- 9 particles per mm2, and the titanium alloy
      group had 9 +/- 16 particles per mm2. The cemented group had 5 +/- 4 particles
      per mm2. The difference between the cement group and the hydroxyapatite group was
      statistically significant. The elemental analysis showed that 70% of the
      particles in the hydroxyapatite group had calcium and phosphorus elements. Third
      body particles likely contribute to particulate generation. The results suggest
      that the hydroxyapatite coated components have the potential for producing
      greater amounts of particulate debris. Continued analysis of retrieved components
      for the presence of the third body particles is required.

PMID- 9170372
TI  - Survivorship analysis of cementless meniscal bearing total knee arthroplasty.
AB  - Four hundred seventy-three consecutive cementless cruciate retaining meniscal
      bearing primary total knee replacements were done on 375 patients from May 1985
      to February 1991. These were observed for a 10-year period (average, 5 years).
      Seventeen (3.6%) required change of components because of mechanical failure.
      There were 12 polyethylene fractures or dislocations. There were 5 tibial
      subluxations secondary to ligamentous instability occurring at an average of 21
      months postoperatively. There were 2 component loosenings secondary to bone graft
      resorption (1 femoral, 1 tibial). There were 5 infections (4 Staphylococcus
      aureus, 1 Pseudomonas). Significantly, with the exception of the 2 knees with
      bone graft resorption, there was no component (femoral, tibial, or patellar)
      loosening. Kaplan-Meier survival estimates, using as an endpoint of revision
      surgery for any mechanical reason (polyethylene breakage, polyethylene
      dislocation, or ligamentous instability), showed a survivorship of 94.6% at the 8
      year interval. Survivorship related to mechanical loosening of fixation of any
      component at the 8-year interval was 99%.

PMID- 9170373
TI  - Total knee arthroplasty for corticosteroid associated avascular necrosis of the
      knee.
AB  - Despite their age, patients younger than 50 years who have collapse of their
      femoral condyles caused by steroid associated avascular necrosis have few options
      except total knee arthroplasty. There have been no specific reports of the
      results of total knee replacements for this disease. Between 1980 and 1993, 31
      porous coated anatomic total knee replacements were performed in 21 patients
      younger than 50 years of age with avascular necrosis of the femoral condyles and
      tibial plateaus. There were 17 women and 4 men, with an average age of 36 years
      (range, 22-48 years). Seventeen of 21 patients had systemic lupus erythematosus,
      and all patients had a history of corticosteroid use. Patients underwent a
      complete clinical and radiographic evaluation at final followup that averaged 8.2
      years (range, 2-16 years). Overall, there were 17 good and excellent results
      (55%). Eleven knees were revised for aseptic loosening (37%), and 3 additional
      knees (10%) ultimately were revised for deep sepsis. All 6 knees in patients with
      no diagnosis of systemic lupus erythematosus had excellent clinical results.
      There were only 11 of 25 successful outcomes (44%) in the patients with systemic
      lupus erythematosus. There were no differences in results when patients were
      stratified by degree of steroid use, cemented versus cementless fixation, or
      activity level.

PMID- 9170374
TI  - Arthroplasty for rheumatoid forefoot deformities by a shortening oblique
      osteotomy.
AB  - Seventy-five feet in 47 patients (46 women, 1 man) who had rheumatoid arthritis
      were observed for an average of 6 years (range, 4-11 years) after an operation on
      the forefoot that included a shortening oblique osteotomy of the metatarsal neck
      of the lateral toes. In addition, patients underwent either flexible hinge toe
      implant arthroplasty or Mitchell's osteotomy in the first metatarsophalangeal
      joint. Forty-two feet (56%) looked normal with no valgus or dorsal displacement
      of the toes. Recurrence of callosities occurred in 9 feet (12%) with moderate
      pain in 3 feet. Thirty-nine (83%) patients were satisfied with the outcome after
      surgery. Resection arthroplasty often is recommended for management of forefoot
      deformities. However, as shown in this series, the improvement in deformities,
      function, and cosmesis of metatarsophalangeal joint preservation may be better
      with an osteotomy of the metatarsal neck than with a resection arthroplasty.
      Because of the development of combined drug therapy, the benefits of synovectomy,
      osteotomy, and shortening in length should be reconsidered. The authors' studies
      suggest that the shortening oblique osteotomy should be considered 1 of the
      surgical reconstruction options for patients with rheumatoid arthritis who have
      forefoot deformities.

PMID- 9170375
TI  - Resistance to activated protein C and Legg-Perthes disease.
AB  - Thrombophilia may cause thrombotic venous occlusion in the femoral head, with
      venous hypertension and hypoxic bone death, leading to Legg-Perthes disease.
      Resistance to activated protein C, the most common thrombophilic trait, was
      measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid
      was studied to delineate the CGA-->CAA substitution at position 1691 of the
      Factor V Leiden gene responsible for resistance to activated protein C. The
      activated protein C ratio was calculated by dividing clotting time obtained with
      activated protein C-calcium chloride by clotting time obtained with calcium
      chloride alone. Resistance to activated protein C, with a low activated protein C
      ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was
      the most common coagulation defect, found in 23 of 64 children with Legg-Perthes
      disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg
      Perthes disease had a low activated protein C ratio and the mutant Factor V gene
      (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or
      3 generation vertical and horizontal transmission of heterozygosity for the
      mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg
      Perthes disease, only 14 (22%) had entirely normal coagulation measures.
      Resistance to activated protein C appears to be a pathogenetic cause of Legg
      Perthes disease.

PMID- 9170376
TI  - Sensitivity of objective parameters in the diagnosis of pediatric septic hips.
AB  - This study examines the sensitivity of temperature, leukocyte count, and
      erythrocyte sedimentation rate in the diagnosis of pediatric septic arthritis of
      the hip by retrospective case analysis of 26 children, aged 0 to 6 years, in
      hospitals of central Brooklyn. The average presenting temperature was 38.4
      degrees C, with 65% of the patients having had a temperature higher than 38
      degrees C. The average leukocyte count was 13,500 per mL, with 73% of patients
      having a leukocyte count greater than 9000 per ml. The average erythrocyte
      sedimentation rate (21 cases) was 51 mm per hour, with 95% of the patients
      presenting with an erythrocyte sedimentation rate greater than 20 mm per hour. Of
      these children with septic hips, only 5% had a normal erythrocyte sedimentation
      rate, although 35% had a normal temperature and 27% had a normal leukocyte count.
      Neonates (age younger than 1 month) were not febrile (average temperature, 36.7
      degrees C) and did not have an elevated leukocyte count (average leukocyte count,
      9300 per mL) but did have an elevated erythrocyte sedimentation rate (average
      erythrocyte sedimentation rate, 45 mm per hour). Of these 3 values, erythrocyte
      sedimentation rate is the most sensitive indicator of septic arthritis of the hip
      in children 0 to 6 years of age.

PMID- 9170378
TI  - Use of osteonics UHR hemiarthroplasty for fractures of the femoral neck.
AB  - A clinical and radiographic study of bipolar hip arthroplasties was performed for
      fractures of the femoral neck. All patients were treated with the Osteonics UHR
      system. Clinical results were evaluated in 77 patients (77 hips) who were
      observed for an average of 4.8 years (range, 2-10 years). At the latest followup,
      67 (87%) patients were rated as having a good or excellent outcome according to
      the Hospital for Special Surgery hip rating system. Clinical ratings in patients
      treated with cementless UHR were similar to or better than those of patients with
      cemented UHR. Hip dislocation occurred in only 3 (2.3%) patients, in whom the hip
      joint was reduced by a closed procedure without inducing disassembly of the
      prosthetic components. None of the patients had definitive acetabular erosion.
      The motion of the outer head was evaluated radiographically in 63 patients in
      weightbearing and non-weightbearing conditions, 3 to 108 months after surgery.
      The relative motion at the 2 sites of articulation of the outer head had
      stabilized by 3 months after surgery and subsequently remained unchanged. The
      authors' findings indicate that UHR hemiarthroplasty of the femoral head is a
      reliable treatment for fractures of the femoral neck.

PMID- 9170377
TI  - Dynamic external fixation for distal radius fractures.
AB  - Thirty adult patients with closed comminuted and mostly intraarticular fractures
      of the distal radius were treated by closed reduction and immobilization with a
      dynamic external wrist fixator during a 2-year period. In 13 patients with
      severely comminuted and unstable fractures, additional Kirschner wires were used.
      After 10 to 14 days of rigid fixation in neutral position, the motion element was
      unlocked to allow up to 30 degrees flexion. Six weeks later, the fixator was
      removed. The patients then were observed for an average of 24 weeks. An excellent
      functional outcome was seen in 6 patients (20%), a good outcome in 20 patients
      (67%), and a fair outcome in 4 patients (13%). Anatomically, 15 patients (50%)
      had an excellent result, 14 (47%) a good outcome, and 1 (3%) a fair outcome. Only
      minimal loss of reduction averaging 1 degree palmar tilt was seen during
      mobilization. There were 2 major complications: 1 deep Kirschner wire tract
      infection and 1 index metacarpal fracture. Minor complications such as sensory
      disturbances and pin tenderness were present but recovered completely after
      removal of the fixator. This study provides promising data and offers an
      alternative method in the treatment of distal radius fractures with severe
      comminution. In cases with postreductive unstable fragments, additional Kirschner
      wires should be used to allow early mobilization of the wrist.

PMID- 9170379
TI  - Reamed interlocking intramedullary nailing of open fractures of the tibia.
AB  - One hundred twelve open tibial fractures were treated by reamed interlocking
      nailing in 108 patients. There were 31 (28%) Grade I fractures, 38 (34%) Grade
      II, 23 Grade IIIA (21%), and 20 (18%) Grade IIIB fractures. Early amputation was
      performed in 2 (10%) Grade IIIB fractures for severe crushing injuries.
      Compartment syndrome complicated 8 (7%) fractures. Mean time to union was 29
      weeks for Grade I fractures, 32 weeks for Grade II, 34 weeks for Grade IIIA, and
      39 weeks for Grade IIIB. Nonunion complicated 9 (8%) fractures: 1 (3%) Grade I
      fracture, 2 (5%) Grade II fractures, 3 (13%) Grade IIIA fractures, and 3 (17%)
      Grade IIIB fractures. Deep infection complicated 4 Grade II fractures (10%) and 2
      (11%) Grade IIIB fractures. Reamed locking intramedullary nailing is a safe and
      effective technique for management of open tibial fractures.

PMID- 9170380
TI  - Outcome after reinfection following reimplantation hip arthroplasty.
AB  - Between 1976 and 1992, reinfection developed in 34 patients treated for an
      infected total hip arthroplasty with removal of the prosthesis and implantation
      of another prosthesis. These patients included 15 men and 19 women with a mean
      age of 62 years. Infection recurred an average of 2.2 years after reimplantation
      of the new prosthesis. Followup after the diagnosis of reinfection averaged 5.1
      years. Reinfection after an attempt at reimplantation total hip arthroplasty was
      seldom compatible with a good functional outcome. Resection arthroplasty was
      reliable in eradicating reinfection but led to poor function and was associated
      with persistent pain. Although reimplantation of a third prosthesis allowed 3
      patients to achieve an excellent result, the 8 hips that failed a third
      reimplantation attempt had the worst functional results in this study. The
      results from the present series suggest that reinfection after an attempt at
      reimplantation is a contraindication to further attempts at a 1-stage
      reimplantation of another prosthesis. Those patients in whom the same single
      microorganism has been identified from the failed primary total hip and from the
      failed first reimplantation, however, may be reasonable candidates for an attempt
      at a 2-stage reimplantation of a third prosthesis, particularly when a deficiency
      in prior antibiotic therapy or surgical technique can be identified.

PMID- 9170381
TI  - Giant cell tumor of bone. Prognosis and treatment of pulmonary metastases.
AB  - Giant cell tumor of bone is a challenging clinicopathologic entity. Despite its
      benign designation, it has the capacity to recur locally and develop rare
      pulmonary metastases. Between 1945 and 1991, 104 patients with histologically
      benign giant cell tumors of bone, 5 of which metastasized to the lung, were
      treated at the authors' institution. In these cases, histologic materials from
      the lung were identical to those found in the primary bone lesion. The primary
      bone lesions were treated with local curettage (3), wide resection (1), and wide
      resection with prosthesis placement (1). The patients were observed for a mean of
      12.6 years (range, 5-38 years). Four of the 5 patients experienced local
      recurrences (average time interval, 34 months), with 3 patients experiencing 2 or
      more recurrences. The average time to lung metastasis was 23 months; 1 patient
      presented initially with pulmonary findings. Four patients underwent surgical
      resection of pulmonary metastases. All 4 patients are alive with no disease
      progression, despite incomplete pulmonary resections in 2 patients. Locally
      aggressive disease and multiple recurrences appear to be risk factors for
      pulmonary metastases in benign giant cell tumor of bone. Pulmonary metastases
      occurred within the first few years after discovery of primary bone tumors.
      Radiographs and computed tomographs of the chest are recommended to rule out this
      complication in patients with local recurrences. Resection of pulmonary
      metastasis is recommended. Long term survival is not incompatible with persistent
      pulmonary lesions.

PMID- 9170382
TI  - Cystic hygroma of the shoulder region. A case report.
AB  - Cystic hygroma is a rare congenital malformation of the lymphatic system. The
      lesion is characterized by the formation of a cystic mass of variable size. Most
      lesions are present in infancy or early childhood and are found predominantly in
      the region of the head and neck. This report describes a case with an unusual
      location of the lesion: A 12-year-old boy with a cystic hygroma in the shoulder
      presented with shoulder pain and swelling. The diagnosis was made by magnetic
      resonance imaging and confirmed after histologic examination of the resected
      specimen. This uncommon localization and condition of cystic hygroma should be
      included in the differential diagnosis of shoulder pain in children.

PMID- 9170383
TI  - Lymphoreticular dissemination of metal particles after primary joint
      replacements.
AB  - Twenty-three patients with a history of primary joint replacement followed by
      lymph node dissection procedure were studied. These specimens included pelvic,
      gastric, paraaortic, inguinal, retroduodenal, and axillary node chains. The lymph
      node specimens were sectioned, processed for scanning electron microscopic study,
      and viewed with backscattered electron imaging to identify metal particles. On
      detection of a metal particle, energy dispersive x-ray microanalysis was
      conducted to determine its elemental composition. Seven of 23 patients had metal
      alloy particles within the lymph node specimens. Metal particles were identified
      in the pelvic and axillary node chains. In each case, the metal alloy identified
      corresponded with the implanted type of alloy. The shortest interval between
      joint implantation and dissemination of metal to a lymph node chain was 6 months.
      These data suggest the need for continued followup to determine long term
      effects, if any, of this distribution of metal particles through the lymphatic
      system.

PMID- 9170384
TI  - Screw placement in the lumbar vertebral isthmus.
AB  - Anatomic parameters of the isthmus from L1 to L5 were measured in 30 dried lumbar
      spines. All measured parameters were fairly constant from L1 to L5. The mean
      values of the core length, thickness of the superior and inferior borders of the
      isthmus, superoinferior diameter and posterior and medial inclinations of the
      lumbar isthmus at L5 were 39.9 +/- 2.3 mm, 2.0 +/- 0.9 mm, 8.9 +/- 1.0 mm, 13.2
      +/- 2.5 mm, 35.9 degrees +/- 5.7 degrees and 31.8 degrees +/- 6.3 degrees,
      respectively. This study shows that a 40 mm long, 4 to 5 mm diameter screw should
      be inserted in the lumbar vertebral isthmus at an angle of 30 degrees laterally
      and anteriorly.

PMID- 9170385
TI  - Comparison of reconstruction nails for high subtrochanteric femur fracture
      fixation.
AB  - Subtrochanteric osteotomies were created in 18 matched pairs of embalmed
      cadaveric femora. The femora were stabilized with a Synthes, Zimmer, or Richards
      second generation femoral reconstruction nail with retrograde blade or screws.
      The femoral pairs were randomly assigned to groups based on nails used: Synthes
      versus Zimmer, Synthes versus Richards, and Zimmer versus Richards. The
      reconstructions were cyclically loaded in bending for 2000 cycles and then loaded
      to failure. The mean stiffness of the Synthes, Zimmer, and Richards
      reconstructions was 17%, 40%, and 40% of the intact femora, respectively. The
      Richards construct was the strongest, and predominately failed by fracture at the
      distal interlocking screw hole. The Zimmer construct failed by bending of the
      nail at the osteotomy site and fracture of the proximal femoral shaft. The
      Synthes construct was the most flexible and least strong and failed by bending of
      the spiral, retrograde blade with concomitant fracture of the femoral neck. This
      study indicates that fixation of subtrochanteric femur fractures with a Synthes
      spiral blade or Richards or Zimmer reconstruction nails provides stable fixation
      for postoperative loading conditions. However, the Richards and Zimmer nails were
      able to withstand higher loads than was the Synthes nail before failure.

PMID- 9170386
TI  - Protooncogene expression in osteogenesis induced by bone morphogenetic protein.
AB  - In this study, changes in the expression of protooncogenes c-fos and c-myc
      messenger ribonucleic acid were investigated in mice after implantation of bone
      morphogenetic protein. The expression of c-fos showed a biphasic pattern. The
      first increase was observed on Day 1 with the aggregation of round cells. The
      second increase was observed on Day 7 with the appearance of chondroblasts. The
      amount of c-myc messenger ribonucleic acid showed the sustained high levels from
      Days 2 to 7. During this period, the proliferation of mesenchymal cells was
      histologically evident. After Day 11, the expression of c-fos and c-myc decreased
      and remained at low levels despite the progress in chondroosteogenesis. The
      protooncogenes c-fos and c-myc appear to increase before calcification in the
      process of bone morphogenetic protein induced bone and cartilage development.

PMID- 9170387
TI  - Generation of free radicals during anoxia and reoxygenation in perfused
      osteoblastlike cells.
AB  - Sensitivity to ischemia and reperfusion injury is a main problem afflicting
      tissues exposed to a prolonged period of oxygen deprivation. The generation of
      oxygen free radicals, in particular, is considered a major cause of postischemic
      reperfusion injury. However, studies on the mechanisms of production of free
      radicals are limited by the difficulty to measure in real time their formation
      and to discriminate between the different oxyradical species. The aim of this
      study was to determine whether the formation of oxygen free radicals occurs in
      murine osteoblastlike cells (MC3T3-E1) exposed to anoxia and reoxygenation and to
      explore its relation to the reoxygenation injury. Cells were cast in agarose and
      perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Anoxia was obtained
      by shifting the gas phase of the media to 95% N2-5% CO2. Oxygen free radicals
      were detected by enhanced chemiluminescence: anion superoxide or hydrogen
      peroxide was measured by adding lucigenin or luminol plus horseradish peroxidase
      to the media, respectively. Cell injury was assessed by the rate of lactate
      dehydrogenase release. During the control period, lucigenin and luminol plus
      horseradish chemiluminescences were 15 +/- 1 nA per chamber and 20 +/- 2 nA per
      chamber, respectively. and lactate dehydrogenase release was 10 +/- 1 mU per
      minute. During anoxia, both chemiluminescences dropped to background levels,
      although lactate dehydrogenase release increased progressively to 38 +/- 7 mU per
      minute. During reoxygenation, O2 formation increased sharply to 45 +/- 6 nA and
      decreased to control levels; H2O2 production increased slowly, reaching 42 +/- 7
      nA at the end of the reoxygenation period; lactate dehydrogenase declined
      progressively to control values. These results show that osteoblastlike cells
      produce measurable amounts of superoxide and hydrogen peroxide radicals during
      reoxygenation. Because lactate dehydrogenase release did not appear to relate to
      chemiluminescence, oxyradical flux may serve as a signal for other events that
      eventually lead to cell injury.

PMID- 9170388
TI  - Histologic examination of meniscal repair in rabbits.
AB  - After a cylindrical defect was made in the anterior segment of the lateral
      meniscus in rabbits, the meniscus was examined postoperatively at 2, 8, and 13
      weeks. Horizontal sections were prepared at a central level of the meniscus from
      each sample and stained with hematoxylin and eosin, Safranin O, and Masson
      trichrome. In addition, part of the tissue was immunologically stained with
      antibodies to chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and
      Type II collagen. Hematoxylin and eosin stained specimens were analyzed for
      repair tissue by microscopic study, and the cells observed in repair tissue were
      found to change from fibroblastlike cells to chondrocytelike cells with the
      progress of repair. Safranin O stained specimens showed a higher stainability
      with the progress of repair, confirming that abundant proteoglycan existed. In
      cases of complete healing, the repair tissue immunostained with antibodies to
      chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, and Type II
      collagen showed a higher stainability than did the surrounding meniscus tissue.
      Thus, it is possible that the repair tissue might have been hyalinelike
      cartilage.

PMID- 9170389
TI  - Electromagnetic fields can affect osteogenesis by increasing the rate of
      differentiation.
AB  - Electromagnetic fields of various kinds can alter osteogenesis in animals with
      osteotomies and patients with nonunions, but the underlying cellular mechanisms
      are unknown. The aims of this study were to determine whether I gauss at 60 Hz
      affected periosteal proliferation and differentiation in either the normal rat
      tibia or 1 to 14 days after a surgically induced defect. In the injured rats,
      using histologic study, autoradiography, and morphometry, it was found that
      exposure for 1 or 3 days had no effect on proliferation but that it produced an
      increase in osteoblasts 3 days after the injury. Proliferation and
      differentiation were unaffected by exposure in the absence of injury. The results
      suggest that the primary effect of the fields was to promote differentiation but
      not proliferation. Because fields can stimulate proliferation of osteoblastlike
      cells in vitro, the results of this study may indicate the presence of an in vivo
      factor that antagonizes the tendency of fields to increase mitotic activity.

PMID- 9170390
TI  - Soft tissue mass in the foot of a 39-year-old woman.

PMID- 9170391
TI  - Magnetic resonance imaging of the musculoskeletal system. Part 8. The spine,
      section 1.
AB  - Magnetic resonance has assumed a preeminent role in the imaging evaluation of the
      spine. Owing to its multiplanar capability and superior soft tissue contrast,
      magnetic resonance imaging is the procedure of choice for a host of spinal
      disorders including degenerative disc disease, tumor evaluation, trauma, and
      spinal deformities. It represents the most accurate means of distinguishing
      between recurrent disc herniation and epidural fibrosis, and it excels at the
      assessment of many postoperative abnormalities such as infection, adjacent
      segment disc degeneration, and arachnoiditis. Magnetic resonance imaging is also
      helpful in the evaluation of numerous diagnostic challenges that are less well
      resolved by other means. This includes the distinction between disc herniation
      and epidural hematoma, synovial cyst from nonspecific fibrous thickening of a
      facet capsule, and the evaluation of numerous other soft tissue abnormalities.
      Computed tomography, computed tomography myelography, and scintigraphy continue
      to be useful for numerous specific disorders and in those patients with metal
      hardware or contraindications to magnetic resonance scanning. Overall, however,
      magnetic resonance is the imaging procedure preferred for many spinal disorders.
      This article is the first installment of a 3-part series discussing the role of
      magnetic resonance imaging of spinal disorders. Section 1 will describe the
      varying imaging modalities available and their relative advantages and
      disadvantages. A consideration of magnetic resonance imaging techniques will
      follow, followed by a discussion of the imaging manifestations of early
      degenerative disc disease. Section 2 will be devoted to an in depth discussion of
      specific pathologic processes encountered in patients with degenerative disc
      disease. Section 3 will end the series with a consideration of postoperative
      imaging followed by a discussion of spinal deformities, trauma, and neoplasms.

PMID- 9170392
TI  - Deep thoughts on tin men. Fact, fallacy, and future of mechanical circulatory
      support.

PMID- 9170393
TI  - Dystrophinopathy, the expanding phenotype. Dystrophin abnormalities in X-linked
      dilated cardiomyopathy.

PMID- 9170394
TI  - Hypertension, serum angiotensinogen, and molecular variants of the
      angiotensinogen gene among Nigerians.
AB  - BACKGROUND: We evaluated the association among the M235T and T174M variants of
      the angiotensinogen (AGT) gene, plasma AGT, and hypertension status in a sample
      of Nigerians. METHODS AND RESULTS: Participants were selected from the extremes
      of the blood pressure distribution obtained from the population survey of 2509
      men and women aged 25 to 74 years. Cases (hypertensive subjects) were individuals
      who had high blood pressure or were taking antihypertensive medication, and
      control subjects were individuals with low blood pressure who had never taken
      antihypertensive medication. We found a significant association between the M235T
      variant and plasma AGT level. Hypertensive subjects had higher plasma AGT levels
      compared with control subjects. The allele frequencies of the two variants were
      similar in the hypertensive patients and the control subjects. CONCLUSIONS: The
      consistent relationships observed between the M235T variant and the protein
      product and between plasma level of the protein and hypertension status in
      different ethnic groups provide some evidence for a biochemical mechanism linking
      DNA variation in the renin-angiotensin system with the hypertension phenotype.

PMID- 9170395
TI  - Aortic root dilatation in patients with spontaneous cervical artery dissection.
AB  - BACKGROUND: Spontaneous cervical artery dissections are a relatively common cause
      of ischemic stroke in young adults. Their mechanism is unknown, though it is
      generally assumed that an underlying minor form of extracellular matrix defect
      could exist. The present study tested the hypothesis that aortic and cardiac
      morphological abnormalities usually seen in patients with heritable connective
      diseases are more frequent in patients with spontaneous cervical artery
      dissections than in patients without such dissections. METHODS AND RESULTS: We
      performed a case-control study of 28 case patients with spontaneous cervical
      artery dissection and 84 control subjects with an ischemic stroke not due to
      cervical artery dissection. Control subjects were matched to case patients for
      age (+/-5 years), sex, and year of hospitalization. The aortic root was more
      frequently enlarged (ie, diameter > 34 mm) in case patients (56%) than in control
      subjects (15%). Mitral valve prolapse, mitral valve dystrophy, and aortic valve
      dystrophy were more frequent in case patients than in control subjects. In
      multivariate analyses, aortic diameter > 34 mm was the only variable associated
      with an increased risk of spontaneous cervical artery dissection (odds ratio,
      14.2; 95% CI, 3.2 to 63.6; P < .001). CONCLUSIONS: These results suggest that
      aortic root diameter enlargement is associated with an increased risk of
      spontaneous cervical artery dissection. This finding is consistent with the idea
      that a generalized defect of the extracellular matrix is present in patients with
      spontaneous cervical artery dissection.

PMID- 9170396
TI  - Transballoon intravascular ultrasound imaging during balloon angioplasty in
      animal models with coarctation and branch pulmonary stenosis.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) studies performed after balloon
      dilation provide a method for evaluating the adequacy of angioplasty and the
      nature of associated changes in vessel walls. Previously, IVUS studies required
      the use of separate scanning catheters inserted independently before and after
      balloon angioplasty. We tested a 0.035-in, 30-MHz IVUS transducer wire that
      images from within commercially available 5F balloon dilation catheters. METHODS
      AND RESULTS: Seven stenoses were created in the left pulmonary artery (n = 3) and
      in the aortic isthmus (n = 4) in six lambs (weight, 3.4 to 12.5 kg). The balloon
      catheter selected was advanced across the stenotic area and the IVUS wire
      advanced in the guide lumen to the center of the balloon. Continuous IVUS images
      were obtained through balloons before, during, and after dilation. Transballoon
      imaging confirmed balloon location within the stenotic segment. Luminal diameters
      of stenotic and adjacent vessel segments before and after angioplasty by IVUS
      showed good correlation with angiographic measurements (r = .93, P < or = .001).
      After successful dilation, imaging during deflation allowed the assessment of
      vascular elastic recoil, mural dissection, and luminal size without requiring
      changes in balloon position. Repeat dilation could be undertaken and the
      inflation pressure and technique modified on the basis of the observed results.
      CONCLUSIONS: This transballoon IVUS system provides important on-line information
      about lumen diameter and wall structure for evaluation of angioplasty without the
      need for catheter changes, providing a method to possibly reduce the likelihood
      of excessive wall damage and to potentially reduce the number of angiograms
      required to accomplish and confirm results.

PMID- 9170397
TI  - ACE gene polymorphism: ischemic heart disease and longevity in 10,150
      individuals. A case-referent and retrospective cohort study based on the
      Copenhagen City Heart Study.
AB  - BACKGROUND: Homozygosity for the deletion allele (D) of the angiotensin
      converting enzyme (ACE) gene insertion-deletion polymorphism has been suggested
      to be a potent risk factor for myocardial infarction. With one exception, the
      samples studied so far have been small and/or ethnically heterogeneous, and most
      investigators have studied men only. METHODS AND RESULTS: We investigated the
      association between ACE genotype and myocardial infarction as well as other
      manifestations of ischemic heart disease for both women and men in a case
      referent study (n = 10,150) as well as in a retrospective cohort study (n =
      7263). The cohort was from the ethnically homogeneous Danish population. Case
      subjects were from the same geographic area and had ischemic heart disease.
      Irrespective of the assumed degree of relative penetrance of the D allele, the
      odds ratios were not significantly different from 1.0 (P > .05) for ischemic
      heart disease, severe stenosis on coronary angiography, or myocardial infarction.
      There was also no association between ACE genotype and phenotypic variation in
      recognized risk factors for ischemic heart disease. Finally, the relative
      frequency of the D allele did not change as a function of age in subjects aged
      from 20 to > or = 80 years. CONCLUSIONS: In two large studies, a case-referent
      study and a retrospective cohort study in an ethnically homogeneous white
      population, there was no evidence for a statistically significant difference in
      the development of myocardial infarction or any other manifestations of ischemic
      heart disease between genotype classes of the ACE gene polymorphism in either
      women or men.

PMID- 9170399
TI  - A prospective study of passive smoking and coronary heart disease.
AB  - BACKGROUND: Several epidemiological studies have suggested an association of
      passive smoking with coronary heart disease (CHD). However, few studies have
      taken account of exposure to passive smoking in the workplace. Additionally,
      several studies have been unable to control for the full range of potential
      confounding factors. We examined prospectively the relationship of passive
      smoking with risk of CHD in a cohort of women. METHODS AND RESULTS: The study was
      carried out in an ongoing prospective cohort of US female nurses, in whom we
      assessed exposure to passive smoking at home and at work as well as duration of
      years spent living with someone who smoked regularly. We studied 32046 women 36
      to 61 years of age in 1982 who had never smoked and were free of diagnosed CHD,
      stroke, and cancer. During 10 years of follow-up (1982 to 1992), 152 incident
      cases of CHD (127 nonfatal myocardial infarction and 25 fatal CHD) occurred.
      Compared with women not exposed to passive smoking, the relative risks of total
      CHD-adjusted for a broad range of cardiovascular risk factors-were 1.58 (95% CI,
      0.93 to 2.68) among those reporting occasional exposure and 1.91 (95% CI, 1.11 to
      3.28) among women reporting regular exposure to passive smoking at home or work.
      There was no relation apparent between duration of living with a smoker and risk
      of CHD. CONCLUSIONS: Despite the fact that exposure to passive smoking was
      assessed by self-report and only at baseline (as well as other limitations),
      these data suggest that regular exposure to passive smoking at home or work
      increases the risk of CHD among nonsmoking women.

PMID- 9170398
TI  - Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac
      events in patients with healed myocardial infarction. Secondary Prevention Group.
AB  - BACKGROUND: The administration of calcium antagonists to patients with healed
      myocardial infarction is a controversial treatment. This study was conducted to
      elucidate the effect of short-acting nifedipine and diltiazem on cardiac events
      in patients with healed myocardial infarction. METHODS AND RESULTS: A controlled
      clinical open trial of 1115 patients with healed myocardial infarction was
      carried out between 1986 and 1994. The patients included 595 who received no
      calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who
      received short-acting diltiazem 90 mg/d. The primary end points were cardiac
      events, which were defined as fatal or nonfatal recurrent myocardial infarction;
      death from congestive heart failure; sudden death; and hospitalization because of
      worsening angina, congestive heart failure, or premature ventricular
      contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium
      antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio,
      1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not
      reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial
      effects of these drugs for reducing cardiac events in patients with such
      complications as hypertension or angina pectoris. CONCLUSIONS: This study showed
      that use of short-acting nifedipine and diltiazem in this postmyocardial
      infarction population was associated with a 24% higher cardiac event rate, but
      this strong adverse trend did not reach statistical significance.

PMID- 9170400
TI  - Fibrinolytic variables and cardiovascular prognosis in patients with stable
      angina pectoris treated with verapamil or metoprolol. Results from the Angina
      Prognosis study in Stockholm.
AB  - BACKGROUND: Disturbed fibrinolytic function may influence the progression of
      coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events.
      METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients
      with stable angina pectoris were studied prospectively during double-blind
      treatment with metoprolol or verapamil. Various measures of fibrinolytic function
      were studied in 631 (of 809) patients. During a median follow-up time of 3.2
      years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal
      myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of
      tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen
      activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were
      determined at baseline and after 1 month's treatment and were related to
      subsequent fatal and nonfatal CV events. Univariate Cox regression analysis
      revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P
      < .05), and low TPA-ag responses to exercise (P < .05) were associated with
      increased risk of subsequent CV death. After adjustment for baseline risk
      factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1
      activity independently predicted CV death or MI in male patients. Verapamil
      treatment was associated with a 10% decrease of TPA-ag levels and metoprolol
      treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS:
      Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well,
      independently predict subsequent CV death or MI in patients with stable angina
      pectoris.

PMID- 9170401
TI  - Induction of cytokine expression in leukocytes by binding of thrombin-stimulated
      platelets.
AB  - BACKGROUND: Activated platelets tether and activate myeloid leukocytes. To
      investigate the potential relevance of this mechanism in acute myocardial
      infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion
      and the occurrence of leukocyte-platelet conjugates in patients with AMI. METHODS
      AND RESULTS: We obtained peripheral venous blood samples in 20 patients with AMI
      before and daily for 5 days after direct percutaneous transluminal coronary
      angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the
      study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed
      increased leukocyte-platelet adhesion in patients with AMI compared with control
      patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 versus 35
      +/- 9; P = .003). In vitro, thrombin-stimulated fixed platelets bound to
      neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for
      interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in
      unfractionated leukocytes. After 4 hours, IL-1 beta and IL-8 concentration of the
      cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively,
      and cellular MCP-1 content had increased by 170 +/- 8%. Addition of activated
      platelets to adherent monocytes had a similar effect and was associated with
      nuclear factor-kappa B activation. Inhibition of binding by anti-P selectin
      antibodies reduced the effect of activated platelets on cytokine production.
      CONCLUSIONS: In patients with AMI, leukocyte-platelet adhesion is increased.
      Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes.
      Our findings suggest that leukocyte-platelet adhesion contributes to the
      regulation of inflammatory responses in AMI.

PMID- 9170402
TI  - Aortic valve replacement for aortic stenosis with severe left ventricular
      dysfunction. Prognostic indicators.
AB  - BACKGROUND: Aortic valve replacement for aortic stenosis (AS) carries an
      increased risk in the presence of left ventricular (LV) systolic dysfunction. Few
      data are available on the outcome of such patients. METHODS AND RESULTS: Between
      1985 and 1992, 154 consecutive patients (107 men and 47 women) with LV systolic
      dysfunction (ejection fraction [EF] < or = 35%) underwent aortic valve
      replacement for AS. The mean preoperative characteristics included EF, 27 +/- 6%;
      aortic valve mean gradient, 44 +/- 18 mm Hg; aortic valve area, 0.6 +/- 0.2 cm2;
      and cardiac output, 4.1 +/- 1.5 L/min. Simultaneous coronary artery bypass graft
      surgery was performed in 78 patients (51%). Perioperative (30-day) mortality was
      9% (14 of 154 patients). Fifty patients died during follow-up. Coronary artery
      disease (P = .002) and a reduced preoperative cardiac output (P = .03) were
      significantly related to reduced overall survival rate by multivariate analysis.
      Postoperative improvement occurred in most patients; 88% were New York Heart
      Association class III or IV before surgery versus 7% after surgery. Postoperative
      EF was assessed in 76% of survivors; 76% of these demonstrated improvement. By
      multivariate analysis, change in EF was inversely related to coronary disease (P
      = .002) and preoperative aortic valve area (P = .03). CONCLUSIONS: Despite LV
      dysfunction, the risk of aortic valve replacement for AS was acceptable and
      related to coronary artery disease and mean aortic gradient, and long-term
      survival was related to coronary disease and cardiac output. Improvement in
      symptoms and EF occurred in most patients.

PMID- 9170403
TI  - Effects of exercise during long-term support with a left ventricular assist
      device. Results of the experience with left ventricular assist device with
      exercise (EVADE) pilot trial.
AB  - BACKGROUND: Long-term implantation of a left ventricular assist device (LVAD) may
      be a future alternative treatment for end-stage heart failure. The objective of
      the present study was to determine the hemodynamic effects of supine bicycle
      exercise and functional capacity during upright treadmill exercise in 10 patients
      after LVAD implantation placed for refractory heart failure as a bridge to
      cardiac transplantation. METHODS AND RESULTS: With supine bicycle exercise, 46 +/
      25 days after device placement, heart and LVAD rates increased in parallel from
      87 +/- 12 to 117 +/- 14 bpm and 82 +/- 18 to 107 +/- 21 bpm, respectively. Peak
      O2 consumption was 8.2 +/- 1.7 mL O2.kg-1.min-1. Fick Systemic blood flow rose
      from 5.0 +/- 1.2 to 7.8 +/- 2.5 L/min. Right atrial and pulmonary capillary wedge
      pressures increased from 6 +/- 4 and 5 +/- 3 mm Hg to 12 +/- 5 and 13 +/- 8 mm
      Hg, respectively. End-diastolic left ventricular dimension increased from 3.9 +/-
      1.3 to 4.8 +/- 1.6 cm; however, right ventricular dimension decreased from 3.2 +/
      1.0 to 2.3 +/- 0.9 cm. With upright treadmill exercise, peak O2 consumption was
      14.1 +/- 2.9 mL O2.kg-1.min-1. CONCLUSIONS: This study indicates that exercise
      during long-term LVAD support is safe and is not limited by right heart
      decompensation. It also justifies a larger study to examine how exercise after
      LVAD implantation compares with that after cardiac transplantation.

PMID- 9170404
TI  - Serial assessment of the cardiovascular system in normal pregnancy. Role of
      arterial compliance and pulsatile arterial load.
AB  - BACKGROUND: Temporal changes in systemic arterial compliance and wave propagation
      properties (pulsatile arterial load) and their role in ventricular-systemic
      arterial coupling during gestation have not been explored. Noninvasive methods
      combined with recently developed mathematical modeling techniques were used to
      characterize vascular and left ventricular (LV) mechanical adaptations during
      normal gestation. METHODS AND RESULTS: Fourteen healthy women were studied at
      each trimester of pregnancy and again postpartum. Experimental measurements
      included instantaneous aortic pressure (subclavian pulse tracings) and flow
      (aortic Doppler velocities) and echocardiographic imaging of the LV. A small
      increase in LV muscle mass and end-diastolic chamber dimension occurred by late
      gestation, with no significant alterations in myocardial contractility. Cardiac
      output increased and the steady component of arterial load (total vascular
      resistance) decreased during pregnancy. Several changes in pulsatile arterial
      load were noted: Global arterial compliance increased (approximately 30%) during
      the first trimester and remained elevated thereafter. The magnitude of peripheral
      wave reflections at the aorta was reduced. The mathematical model-based analysis
      revealed that peripheral wave reflections at the aorta were delayed and that both
      conduit and peripheral vessels contributed to the increased arterial compliance.
      Finally, coordinated changes in the pulsatile arterial load and LV properties
      were responsible for maintaining the efficiency of LV-to-arterial system energy
      transfer. CONCLUSIONS: The rapid time course of compliance changes and the
      involvement of both conduit and peripheral vessels are consistent with reduced
      vascular tone as being the main underlying mechanism. The pulsatile arterial load
      alterations during normal pregnancy are adaptive in that they help to accommodate
      the increased intravascular volume while maintaining the efficiency of
      ventricular-arterial coupling and diastolic perfusion pressure.

PMID- 9170405
TI  - Local capture by atrial pacing in spontaneous chronic atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is considered to be maintained by multiple
      reentrant circuits without or with a very short excitable gap. However, the
      possibility of local atrial capture has been shown recently in experimental AF or
      induced AF in humans. METHODS AND RESULTS: This study was undertaken to evaluate
      the feasibility of atrial capture-suggestive of an excitable gap-in spontaneous
      chronic AF. Decremental pacing was performed in 47 right atrial sites in 14
      patients with chronic AF, not taking antiarrhythmic drugs. A Franz catheter (for
      pacing and monophasic action potential recording) and a recording quadripolar
      catheter positioned about 10 mm apart were used. Local capture was achieved in 41
      (87.2%) sites for a total of 100 captures. In 71 episodes the capture was lost
      within 15 seconds, while in the remaining 29, pacing was stopped after 15 seconds
      of stable capture. AF types immediately before capture were type 1 in 83 and type
      2 in 17 episodes. Type 3 AF was never captured. Pacing cycle at capture was 175.7
      +/- 20.9 ms. The baseline atrial interval (FF) was 185.4 +/- 24.5, significantly
      longer than the FF recorded during pacing immediately before capture (176.0 +/-
      19.8 ms) (P < .02). CONCLUSIONS: During spontaneous chronic AF in humans, (1)
      local capture by atrial pacing is possible up to at least 15 mm from the pacing
      site, (2) regional entrainment is possible during type 1 and type 2 AF but not
      type 3 AF, and (3) pacing before capture accelerates AF, probably by transient or
      local capture. These findings suggest that an excitable gap is present in chronic
      AF, therefore supporting the hypothesis that leading circle reentry is not the
      unique electrophysiological mechanism maintaining the arrhythmia.

PMID- 9170406
TI  - Quantitative assessment of alterations in regional left ventricular contractility
      with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry
      and pressure-volume relations.
AB  - BACKGROUND: Tissue Doppler imaging (TDI) is a novel method of color-coding
      myocardial velocity on-line. The objective of the present study was to evaluate
      endocardial velocity with TDI as a method of objectively quantifying alterations
      in regional contractility over a wide range induced by inotropic modulation.
      METHODS AND RESULTS: Myocardial length crystals were used to simultaneously
      assess regional left ventricular (LV) function, and high-fidelity pressure and
      conductance catheters were used to assess global LV contractility by pressure
      volume relations in nine open-chest dogs. Mid-LV M-mode and two-dimensional color
      TDI images were recorded during control and inotropic modulation stages with
      dobutamine and esmolol. Predicted significant increases in TDI indices occurred
      with dobutamine: peak systolic velocity of 4.41 +/- 1.07 to 6.67 +/- 1.07 cm/s*,
      systolic time-velocity integral (TVI) of 0.43 +/- 0.12 to 0.62 +/- 0.10 cm*, and
      diastolic TVI of 0.49 +/- 0.11 to 0.71 +/- 0.17 cm*. Opposing significant
      decreases occurred with esmolol: peak systolic velocity of 4.46 +/- 0.94 to 2.31
      +/- 0.81 cm/s*, systolic TVI of 0.47 +/- 0.12 to 0.19 +/- 0.11 cm*, and diastolic
      TVI of 0.55 +/- 0.11 to 0.33 +/- 0.11 cm* (*all P < .001 versus control). Changes
      in TDI peak systolic velocity were correlated with changes in fractional
      shortening (r = .88) and shortening velocity (r = .87) by sonomicrometry. Changes
      in TDI peak velocity from multiple mid-LV sites also correlated significantly
      with maximal elastance (r = .85 +/- .04) from pressure-volume relations.
      CONCLUSIONS: TDI measures reflect directional and incremental alterations in
      regional and global LV contractility and have the potential to quantify regional
      LV function.

PMID- 9170407
TI  - Evidence for a dystrophin missense mutation as a cause of X-linked dilated
      cardiomyopathy.
AB  - BACKGROUND: X-linked dilated cardiomyopathy (XLCM) has previously been shown to
      be due to mutations in the dystrophin gene, which is located at Xp21. Mutations
      in the 5' portion of the gene, including the muscle promoter, exon 1, and the
      exon 1-intron 1 splice site, have been reported previously. The purpose of this
      study was to analyze the originally described family with XLCM (and other) for
      dystrophin mutations. METHODS AND RESULTS: Polymerase chain reaction (PCR) was
      used to amplify genomic DNA, and reverse-transcriptase PCR amplified cDNA from
      RNA obtained from heart and lymphoblastoid cell lines. Primers to the muscle
      promoter, brain promoter, and Purkinje cell promoter were designed, in addition
      to the exon 1 to exon 14 regions of dystrophin. Single-strand conformation
      polymorphism analysis was used for mutation detection, and DNA sequencing defined
      the mutation. Protein modeling was used for amino acid and secondary structure
      analysis. A missense mutation in exon 9 at nucleotide 1043 was identified that
      causes an alanine to be substituted for threonine, a highly conserved amino acid,
      at position 279 (T279A). This mutation results in a change in polarity in the
      evolutionarily conserved first hinge region (H1) of the protein and substitution
      of a beta-sheet for alpha-helix in this portion of the protein, destabilizing the
      protein. CONCLUSIONS: A novel missense mutation in exon 9 of dystrophin causing
      an abnormality at H1 leads to the cardiospecific phenotype of XLCM.

PMID- 9170408
TI  - In vivo gene transfection of human endothelial cell nitric oxide synthase in
      cardiomyocytes causes apoptosis-like cell death. Identification using Sendai
      virus-coated liposomes.
AB  - BACKGROUND: Nitric oxide (NO) has various actions on the cardiovascular system,
      although its pathophysiological significance in myocardial cells remains obscure.
      The aim of the present study was to identify direct NO actions on cardiomyocytes
      by gene transfection in vivo using a newly developed vector under physiological
      conditions. METHODS AND RESULTS: Liposomes containing the beta-galactosidase
      (beta-gal) gene alone or with the human endothelial cell nitric oxide synthase
      (ecNOS) gene were coated with UV-inactivated Sendai virus and injected into the
      left ventricular wall of rat heart in vivo. Histological examination confirmed
      that the transfection efficiency was comparable to adenovirus-mediated
      transfection and that the new vector per se caused no inflammation. beta-Gal
      expression was confined to cardiomyocytes between two intercalated discs,
      suggesting that the transfected gene did not permeate the discs. An
      immunohistochemical study showed that cotransfection of the ecNOS gene induced
      massive myocardial cell shrinkage in both transfected cells and the adjacent
      myocytes in a time- and dose-dependent manner. Histochemical findings in shrunk
      cells coincided with apoptosis as identified by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick-end labeling. Electron microscopy of the
      lesion revealed myofibrillar degradation and accumulation of mitochondria but no
      apoptotic bodies. Pre-treatment with the NOS inhibitor N omega-nitro-L-arginine
      methyl ester abolished these morphological alterations. CONCLUSIONS: The
      efficient expression of the human ecNOS gene in vivo suggests that NO or its
      toxic metabolite caused myocardial degradation, a part of which was compatible
      with apoptosis of the transfected cardiomyocytes themselves and the adjacent
      cells as a paracrine effect. These morphological features mimicked acute
      myocarditis or ischemic injury.

PMID- 9170410
TI  - Images in cardiovascular medicine. Myocardial bridges.

PMID- 9170409
TI  - Regulation of fibrillar collagen gene expression and protein accumulation in
      volume-overloaded cardiac hypertrophy.
AB  - BACKGROUND: Interstitial collagen accumulation has been extensively demonstrated
      to be increased at both mRNA and protein levels in pressure-overloaded cardiac
      hypertrophy. However, few data are available regarding the effects of volume
      overload on myocardial collagens. METHODS AND RESULTS: To determine whether the
      alterations of collagens may occur in volume-overloaded cardiac hypertrophy, we
      measured collagen types I and III mRNA levels and protein accumulation in left
      ventricular (LV) myocardium of rats at 3, 7, and 28 days after the creation of an
      aortocaval (AC) shunt. Eccentric LV hypertrophy was produced in rats with AC
      shunting. Northern blot analysis on RNA extracted from LV tissue indicated that
      the steady state mRNA levels for both type I and III collagen were persistently
      upregulated in AC shunt rats compared with sham-operated operated control rats.
      In contrast, the biochemical collagen protein concentration and morphometric
      collagen volume fraction were comparable between sham-operated control and AC
      shunt rats at any study time point. Furthermore, the immunohistochemical staining
      of types I and III collagen and Sirius red staining on myocardial tissue sections
      revealed no significant alterations in the distribution or density of fibrillar
      collagens in AC shunt rats. Tissue collagenase activity was not different between
      control and AC shunt rats after 28 days. CONCLUSIONS: Cardiac volume overload
      increases LV collagen mRNA as does pressure overload. However, in contrast to
      pressure-overloaded hypertrophy, the upregulation of collagen transcriptional
      activity does not result in subsequent myocardial fibrosis in volume-overloaded
      hypertrophy due to AC shunting. Therefore, the upregulation of collagen gene
      expression and protein accumulation might be different in pressure-overloaded and
      volume overloaded hypertrophy.

PMID- 9170411
TI  - Images in cardiovascular medicine. An "ACE' of a test.

PMID- 9170412
TI  - Blind T-cell homeostasis and the CD4/CD8 ratio in the thymus and peripheral
      blood.
AB  - We present a model of the dynamics of CD4 and CD8 T-cell subsets in the thymus
      and peripheral blood and use it to study the blind homeostasis hypothesis, which
      states that the total T-cell population in the periphery is subject to regulation
      rather than regulation of the CD4 or CD8 subsets individually. Our model
      reconstructs experimental observations by Adleman and Wofsy on the effects of
      CD4+ T-cell depletion in mice. Our results point to the importance of the thymus
      in recovery from CD4+ T-cell depletion and particularly to the need to
      hypothesize an intrathymic feedback regulation of T-cell production exerted by
      CD4+ T cells. Our results support the blind homeostasis hypothesis for regulation
      of the peripheral blood levels of CD4+ and CD8- T cells.

PMID- 9170413
TI  - Zidovudine potentiates local and systemic inflammatory responses in the rat.
AB  - The effect of chronic treatment with zidovudine (AZT) on the inflammatory
      response was examined in the rat. AZT was administered orally for 36 days. On day
      35, inflammation was induced by hindpaw injection of 1% carrageenan lambda. Paw
      edema over a 24-hour period was used as a marker of the local inflammatory
      reaction. On day 36, quantification of immunoreactive T-kininogen and alpha 1
      inhibitor-3 in liver and serum was used to assess the systemic inflammatory
      response. Albumin was selected as a protein whose concentration is modified only
      slightly or not at all during the acute-phase response. Animals treated with AZT
      transiently exhibited significantly greater (18%) paw edema 3 hours after
      carrageenan injection. AZT treatment alone induced a 1.8-fold increase in serum T
      kininogen concentration, but it had no effect on albumin and alpha 1-inhibitor-3.
      In rats with inflamed paws, AZT administration led to a significant increase in
      liver (3.4-fold) and serum (1.8-fold) immunoreactive T-kininogen content. Dot
      blot analysis of total RNA isolated from liver correlated with the protein
      measurements. Our results indicate that chronic treatment with AZT potentiates
      the nonspecific local and the systemic inflammatory responses in the rat.

PMID- 9170414
TI  - Correlation between plasma HIV-1 RNA levels and the rate of immunologic decline.
AB  - To determine the influence of HIV-1 replication on immunologic decline and
      clinical outcome, we quantified the HIV-1 plasma viral load in 20 patients at
      different times over a mean period of 10.8 months. Quantitation was performed by
      branched DNA signal amplification (bDNA) and p24 antigenemia. Immunologic status
      was assessed through beta 2-microglobulin and CD4+ cell count determinations.
      CD4+ cell decline was expressed as a slope of the regression line constructed by
      the logarithms of CD4+ cell count observations. Mean values of plasma viral load
      were correlated with CD4+ cell decline and mean beta 2-microglobulin levels.
      Significant correlation was observed between plasma viral load quantified by the
      bDNA technique and CD4+ cell decline. No significant correlation was observed
      between plasma viral load quantified by p24 antigenemia and CD4+ cell decline. A
      significant correlation was observed between plasma viral load and beta 2
      microglobulin levels. Immunologic decline was better predicted from HIV-1 RNA
      levels than from the CD4+ cell count. Significantly higher plasma viral load was
      observed in patients who had clinical progression of HIV-1 infection. Thus, HIV-1
      plasma viral load quantified by a highly reliable technique such as bDNA showed
      that the immunologic decline is closely related to HIV-1 RNA replication.

PMID- 9170415
TI  - Anal cytology as a screening tool for anal squamous intraepithelial lesions.
AB  - Anal squamous intraepithelial lesions (ASIL) are common in homosexual and
      bisexual men, and high-grade ASIL (HSIL) in particular may represent an anal
      cancer precursor. Cervical cytology is a useful screening tool for detection of
      cervical HSIL to prevent cervical cancer. To assess anal cytology as a screening
      tool for anal disease, we compared anal cytology with anoscopy and histopathology
      of anal biopsies. A total of 2958 anal examinations were performed on 407 HIV
      positive and 251 HIV-negative homosexual or bisexual men participating in a
      prospective study of ASIL. The examination consisted of a swab for anal cytology
      and anoscopy with 3% acetic acid and biopsy of visible lesions. Defining abnormal
      cytology as including atypical squamous cells of undetermined significance and
      ASIL, the sensitivity of anal cytology for detection of biopsy-proven ASIL was
      69% (95% confidence interval: 60 to 78) in HIV-positive and 47% (95% confidence
      interval; 26 to 68) in HIV-negative men at their first visit and was 81% and 50%,
      respectively, for all subsequent visits combined. The absence of columnar cells
      did not affect the sensitivity, specificity, or predictive value of anal
      cytology. Anal cytology may be a useful screening tool to detect ASIL,
      particularly in HIV-positive men. The grade of disease on anal cytology did not
      always correspond to the histologic grade, and anal cytology should be used in
      conjunction with histopathologic confirmation.

PMID- 9170417
TI  - Induction of granulocyte colony-stimulating factor by acute febrile infection but
      not by neutropenia in HIV-seropositive individuals.
AB  - The objective of this study was to assess endogenous granulocyte colony
      stimulating factor (G-CSF) serum levels in HIV-seropositive individuals with
      persistent neutropenia or acute febrile infection. Serum levels of G-CSF were
      measured by enzyme-linked immunoabsorbent assay. HIV-seropositive subjects (n =
      28) with afebrile neutropenia (< 1000 neutrophils/microliter) showed low G-CSF
      serum levels (i.e., median was below the detection limit) not different from
      those of healthy volunteers (n = 66) or nonneutropenic HIV-seropositive controls
      (n = 75). In contrast, patients with acute myeloid leukemia and afebrile
      neutropenia from chemotherapy (n = 17) demonstrated markedly elevated G-CSF
      levels (median, 264 pg/ml; p < 0.0001). However, HIV-seropositive patients with
      pneumonia (n = 17) showed increases of G-CSF serum levels (median, 152 pg/ml; p <
      0.0001) similar to HIV-seronegative patients (n = 17) with pneumonia (median, 123
      pg/ml; p = 0.97). The results suggest that there may be a contribution of low G
      CSF serum levels to persistent neutropenia in HIV-seropositive individuals.
      Moreover, the different G-CSF serum levels in HIV-seropositive individuals in
      response to neutropenia or acute febrile inflammation suggest different
      mechanisms for the regulation of G-CSF.

PMID- 9170416
TI  - Definition and diagnosis of cytomegalovirus colitis in patients infected by human
      immunodeficiency virus.
AB  - The definition and routine diagnosis of cytomegalovirus (CMV) colitis in patients
      infected by human immunodeficiency virus (HIV) are controversial. In 100
      consecutive HIV-infected patients who underwent colonoscopy for the investigation
      of diarrhea, we compared the yields of routine diagnostic tools for CMV infection
      and assessed the risk of further CMV organ disease in subgroups of patients with
      the following features: full evidence of CMV colitis (group 1), colonic CMV
      infection but no endoscopic lesions (group 2), and no evidence of colonic CMV
      infection (group 3). All biopsies taken during colonoscopy were examined
      immediately by routine hematoxylin and eosin (H&E) staining and viral culture and
      then pooled for second-line H&E staining and immunohistology. Among the 15
      diagnoses of CMV colitis (group 1), two were missed during initial H&E
      examination, and both patients developed further CMV organ disease during follow
      up. Of the 12 group 2 patients 11 were not receiving anti-CMV drugs at the time
      of initial colonoscopy. CMV organ disease was not significantly more common in
      these patients than in group 3 during follow-up. We conclude that routine H&E
      staining of colonic biopsy specimens for CMV inclusions is not 100% sensitive for
      CMV colitis. The favorable outcome of colonic CMV infection without endoscopic
      lesions suggests that only patients with full evidence of CMV colitis warrant
      specific antiviral therapy.

PMID- 9170418
TI  - Associations of age, immunosuppression, and AIDS among homosexual men in the
      Tricontinental Seroconverter Study.
AB  - To characterize the associations of age, immunosuppression, and AIDS outcomes, we
      evaluated serial measures of CD4+ lymphocytes from 376 homosexual men with
      documented dates of HIV-1 seroconversion registered in the Tricontinental
      Seroconverter Study. Using regression models and adjusting for variation within
      individuals, we found no association between age and the number of CD4+
      lymphocytes at seroconversion or with CD4+ lymphocyte decline after
      seroconversion. Men who developed opportunistic infections had fewer CD4+
      lymphocytes at the time of diagnosis compared with men who developed AIDS
      defining Kaposi's sarcoma. Older age was significantly associated with higher
      numbers of CD4+ lymphocytes in individuals diagnosed with AIDS-defining Kaposi's
      sarcoma but was not significant for individuals with opportunistic infections.
      Because older age shortens the latency period of Kaposi's sarcoma and does not
      affect the CD4+ lymphocyte loss, it results in higher CD4+ lymphocytes at the
      time of diagnosis. These findings suggest distinct biologic mechanisms for
      various AIDS manifestations, which is important for clinical decision making and
      health care planning.

PMID- 9170419
TI  - Morbidity and mortality in European children vertically infected by HIV-1. The
      French Pediatric HIV Infection Study Group and European Collaborative Study.
AB  - Based on 392 infected children enrolled in two European prospective studies of
      infants born to HIV-infected women, with similar standard protocols, HIV disease
      progression in the first 6 years of life is described, using the 1994 CDC
      paediatric HIV classification. Most children had developed minor (A) or
      moderately severe (B) illness in the first 4 years of life, although usually it
      was transient in nature. Progression to U.S. Centers for Disease Control and
      Prevention (CDC) group C disease or HIV-related death is an estimated 20% (95%
      confidence interval 16-24%) during the first year of life, and 4.7% (3.3-6.5%)
      per year thereafter, giving a cumulative incidence of 36% (30-43%) by 6 years.
      The mortality rate at 6 years is 26% (20-32%). Two thirds of the children alive
      at 6 years had only minor symptoms, and one third had a CD4+ cell distribution of
      > 25% despite previous clinical manifestations and a transient period of moderate
      immune deficiency. Differences in zidovudine monotherapy between the two cohorts
      were not associated with the mortality rate. However, the risk of severe
      bacterial infections was lower in the French cohort, in which the use of
      antibacterial prophylaxis was more common. The early, severe form of HIV disease
      affects approximately 20% of infants, and after 6 years 75% of infected children
      are still alive. This has important implications for health-care planning.

PMID- 9170420
TI  - Effect of smoking on the clinical progression of HIV-1 infection.
AB  - Cigarette smoking as a risk factor in progression of HIV-1 disease was
      investigated in the Multicenter AIDS Cohort Study of homosexual men. Longitudinal
      data for T-cell subsets, HIV-related clinical symptoms, smoking behavior, and
      AIDS medication use were collected semiannually from 2,499 HIV-1-seropositive men
      for up to 9 years. Survival methods, including Kaplan-Meier analysis and
      multivariate Cox regression models, were used to assess the effect of cigarette
      smoking on development of Pneumocystis carinii pneumonia (PCP), AIDS, death, and
      self-reported oral thrush. After adjustment for CD4+ lymphocyte count and use of
      antiretroviral and anti-PCP medications, smoking was not significantly associated
      with progression to PCP, AIDS, or death in either the HIV-seroprevalent or
      seroincident cohort members. Among men who had baseline CD4+ cell counts >
      200/microliter, smoking was associated with a 40% increase in the hazard of oral
      thrush (p < or = 0.01). These data indicate that cigarette smoking does not have
      a major effect on the progression of HIV-1 infection to AIDS or death but may
      affect the incidence of oral thrush.

PMID- 9170421
TI  - Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x
      10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group.
AB  - The objective of this study was to assess whether patients with CD4+ cell counts
      <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS
      defining event; 187 patients from the placebo arm of a clinical trial of
      toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis,
      patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte
      count < 200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no
      severe liver, renal, or hematologic abnormalities. We used proportional hazards
      regression to study the relationships between baseline variables. AIDS-defining
      events as time-dependent variables, and survival. The risk of dying was increased
      by 1.9 for a 10-year increase in age and by 1.3 when CD4+ decreased by 50 x
      10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection,
      or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0
      40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining
      events was associated with an increased risk of dying, but the power to detect
      such an association was limited. We conclude that the occurrence of
      pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell
      count are important determinants of survival for HIV1-infected patients with CD4+
      counts < 200 x 10(6)/L who are toxoplasmosis antibody positive.

PMID- 9170422
TI  - Trends in heterosexually acquired AIDS in the United States, 1988 through 1995.
AB  - We used national AIDS surveillance data to characterize trends in the numbers and
      proportions of heterosexually acquired AIDS cases diagnosed from January 1988
      through December 1995 among adults and adolescents. We adjusted for expansion of
      the 1993 AIDS surveillance case definition and for delays in reporting, and we
      redistributed cases initially reported without risk. The chi-square test for
      linear trend was used to analyze trends at the p < 0.01 level by half-year of
      diagnosis and by sex, age, race or ethnicity, geographic region of residence at
      diagnosis, and partner's HIV exposure risk. From 1988 through 1995, heterosexual
      contact accounted for 10% of all AIDS cases. Heterosexual contact increased the
      most rapidly of all HIV exposure modes, with increases found among men and women
      in all age groups; among blacks, whites, and Hispanics: and among persons living
      in all geographic regions of the country. Blacks and Hispanics accounted for 75%
      of all persons reported with AIDS attributed to heterosexual contact. Although
      heterosexual contact with an injection drug user (IDU) accounted for most cases
      until 1993, cases increased most rapidly among persons reporting heterosexual
      contact with an HIV-infected partner whose risk was not specified. Findings
      suggest continued growth of the heterosexual AIDS epidemic. Because of the
      disproportionate and increasing number of heterosexually acquired AIDS cases
      among blacks and Hispanics, black and Hispanic communities at risk for HIV
      infection should be considered a high priority for prevention and education
      programs specifically targeting heterosexually active adolescents and adults.
      Epidemiologic and behavioral research and prevention program evaluation are
      urgent public health priorities to better control and prevent the further spread
      of HIV among heterosexually active adults and adolescents.

PMID- 9170423
TI  - Oral sex and HIV transmission.

PMID- 9170424
TI  - Immune reactivity of HTLV-IIa-infected Kayapo Indians with HTLV-IIb extended Tax
      epitope.

PMID- 9170425
TI  - Differentiated thyroid carcinoma in children and adolescents: a 37-year
      experience in 85 patients.
AB  - This study reports on 85 differentiated thyroid carcinoma (DTC) (72 papillary, 13
      follicular) patients, younger than 18 yr of age at the time of diagnosis,
      consecutively treated during the period 1958-1995. METHODS: Follow-up (median:
      111 mo, range 1-324 mo) consisted of clinical examination, serum thyroglobulin
      (Tg), 131I whole-body scintigraphy (whole-body scan) and other imaging
      procedures. RESULTS: Forty-six patients had undergone total thyroidectomy, 38
      partial thyroidectomy and 1 thyroid biopsy. In 47 patients, lymph-adenectomy was
      also performed. Five patients were treated after surgery by external
      radiotherapy, 59 by 131I therapy and 16 by both modalities. Iodine-131 therapy
      was successful in ablating thyroid remnants in 35/48 cases, lymph node metastases
      in 8/11 cases and lung metastases in 12/16 cases. Among the patients with
      scintigraphic-confirmed disappearance of lung metastases, serum Tg was still
      detectable in 10 cases, but continued to decrease spontaneously even without
      further therapeutic doses of 131I. All patients were still alive after a median
      period of 137 mo (range 5-444 mo). Six patients experienced a recurrence of the
      disease in the neck. Sixty-seven patients were free of disease, 3 had lymph node
      metastases, 4 lung metastases and 11 had detectable levels of Tg without
      demonstrable metastases. No impairment of female fertility or untoward genetic
      effects were noticed. One male patient, treated with 3.33 GBq of 131I, was
      infertile due to oligospermia. One case of gastric cancer and one of breast
      cancer occurred 8 and 19 yr, respectively, after 131I therapy. CONCLUSION: Iodine
      131 therapy is highly effective in reducing lung metastases, but undetectable
      levels of Tg are seldom achieved. Total thyroidectomy and 131I therapy is an
      effective and safe treatment for the majority of patients with DTC diagnosed in
      childhood or adolescence.

PMID- 9170426
TI  - Imaging prostate cancer with technetium-99m-7E11-C5.3 (CYT-351).
AB  - To evaluate the performance of the 99mTc-labeled monoclonal antibody CYT-351 in
      visualizing prostate cancer, radioimmunoscintigraphy (RIS) was performed in 35
      patients. METHODS: Antibody (0.5 mg) labeled with 600 MBq 99mTc was injected
      intravenously after obtaining informed consent. Planar and SPECT imaging was
      performed at 10 min and 6-8 and 22-24 hr postinjection. The scans were evaluated
      for visualization of the primary focus or local recurrence, extraprostatic
      invasion, lymph node involvement and uptake in bone and soft tissue metastases.
      RESULTS: Thirty-six studies in 35 patients were performed. In 13/14 evaluable
      studies with clinically localized prostate cancer, RIS had a true-positive rate
      of 92% (12/13). In eight patients with previous incidental carcinoma detected
      during transurethral resection undertaken for clinically benign disease, there
      were 86% true-positive results (6/7) and one true-negative result, which were
      confirmed by systematic needle biopsies. In six patients with evidence of local
      recurrence after a previous radical prostatectomy, the true-positive rate was
      100% (6/6), which was confirmed by raised or rising prostate-specific antigen
      levels (PSA) and/or by biopsy. In the eight patients with known metastases, the
      disease was visualized in 4/4 with progression but not in the 3/3 with
      regression; one patient demonstrated regressing disease as determined by PSA
      levels. The overall accuracy was 92%. CONCLUSION: RIS with 99mTc CYT-351 is
      capable of providing good quality images and yielding clinically useful
      information safely. It has a potentially important clinical role for patients
      with rising PSA levels but negative images by conventional modalities.

PMID- 9170427
TI  - Comparison of technetium-99m-MIBI and technetium-99m-tetrofosmin uptake by
      musculoskeletal sarcomas.
AB  - Technetium-99m-MIBI was initially developed for heart studies but it can also be
      used to depict tumors, predict multidrug resistance and evaluate chemotherapy.
      Recently, 99mTc-tetrofosmin, which exhibits similar physical properties, has been
      launched for heart studies. Tumor uptake and prediction of multidrug resistance
      have also been reported regarding the latter tracer. A comparison of these two
      tracers regarding the detectability of musculoskeletal sarcoma has been made.
      METHODS: Twenty patients with musculoskeletal sarcoma of the extremities or
      pelvis underwent planar examination after the administration of 99mTc-MIBI and
      99mTc-tetrofosmin with an interval of 2-7 days. The tumor activity was compared
      with one ipsilateral and one contralateral background region. RESULTS: There was
      a small, but not significant, difference in favor of 99mTc-MIBI with regard to
      both background regions. CONCLUSION: Technetium-99m-MIBI and 99mTc-tetrofosmin
      can both be used to visualize musculoskeletal sarcomas. The choice may depend on
      which agent is used routinely for myocardial studies in the laboratory.

PMID- 9170428
TI  - Total-body scintigraphy with thallium-201 and iodine-131 in the follow-up of
      differentiated thyroid cancer.
AB  - We analyzed the significance of total body scintigraphy with 201Tl in the follow
      up of patients with differentiated thyroid cancer, both in the preablation and
      ablated stages. METHODS: Prospective assessment was performed in 116 patients who
      were involved in 178 studies (115 in preablation and 63 after ablation). For
      ablation, an absence of uptake in the thyroid bed was required in the total 131I
      follow-up scan after 131I ablation therapy. Each study consisted of a 201Tl scan
      performed while the patient was receiving thyroid hormone therapy, an 131I scan
      performed when endogenous thyroid-stimulating hormone levels were higher than 50
      mlU/ml and determination of thyroglobulin (Tg) concentration using the same
      sample. RESULTS: In the 115 scans in the preablation group, the findings for
      201Tl and 131I agreed in 26 scans and disagreed in 89 scans. In 59 discordant
      studies, only 131I detected focal accumulation, and, in 54 of these, Tg levels
      were undetectable. Of the other 30 discordant studies, 201Tl and 131I detected
      focal uptake in 27 studies, although they did not reveal the same lesions, and in
      3 studies, only 201Tl detected focal accumulation; in these 30 studies, the
      association of detectable Tg predominated. Of the 63 studies in the ablated
      group, the results agreed for the two tracers in 49 and disagreed in 14 studies.
      In 13 of the 14 discordant studies, 201Tl detected focal uptake, and, in 10 of
      these, Tg was detectable. Thus, 31 of the 116 patients assessed (15 preablation
      and 16 ablated) had at least one lesion that was detected by 201Tl but not
      detected by 131I. A definitive diagnosis could be established in 26 patients, and
      the presence of thyroid cancer was confirmed in 23. The sensitivity and
      specificity in the ablated group were 94% and 96%, respectively, for 201Tl and
      29% and 100%, respectively, for 131I. CONCLUSION: The high sensitivity of 201Tl
      scintigraphy in detecting tumor tissue indicates that the inclusion of this
      technique in the follow-up of patients with differentiated thyroid carcinoma
      should be considered in both the preablation and the ablated stages.

PMID- 9170429
TI  - Standardized uptake value and quantification of metabolism for breast cancer
      imaging with FDG and L-[1-11C]tyrosine PET.
AB  - The aims of the study were to compare the value of L-[1-11C]tyrosine (TYR) and
      [IBF]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast
      cancer, to investigate the correlation between quantitative values and
      standardized uptake values (SUVs) and to estimate the value of SUVs for the
      evaluation of therapy. METHODS: Eleven patients with one or more malignant breast
      lesions and two patients with one or more benign breast tumors were studied with
      TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously.
      All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10
      malignant tumors and the 3 benign lesions, glucose consumption and protein
      synthesis rate were quantified. All lesions were studied using SUVs based on body
      weight, body surface area and lean body mass, with and without correction for
      plasma glucose or tyrosine levels. RESULTS: All malignant tumors were visualized
      with both FDG and TYR, but the visual contrast was better with FDG. Increased
      uptake of the tracers was seen in patients with fibrocystic tissue and
      complicated the visual assessment and the outlining of tumor tissue. Uptake in
      fibrocystic disease was more prominent with FDG than with TYR. No difference in
      tumor/nontumor ratio between the two tracers could be established. FDG showed a
      false-positive result in one benign lesion. No major differences between the SUVs
      as defined above were found, although the best correlation between glucose
      consumption and the SUV was observed when the SUV was based on body surface area
      and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean
      body mass was found to correlate best with protein synthesis rate (r = 0.83
      0.94). CONCLUSION: In this group of patients, TYR appears to be a better tracer
      than FDG for breast cancer imaging, because of lower uptake in fibrocystic
      disease. SUVs correlate well with quantitative values, but future studies must
      determine whether treatment evaluation is also reliable with SUVs.

PMID- 9170430
TI  - Radionuclide therapy of skin cancers and Bowen's disease using a specially
      designed skin patch.
AB  - Skin cancer is the most common malignancy in humans. Therapeutic modalities for
      skin cancer are local destruction, radiotherapy and surgery. External radiation
      therapy leads to good results, however, generally 5-6 wk of treatment is needed
      to deliver optimal radiation dose to tumors. In this study, a beta-emitting
      radionuclide, 166Ho, impregnated in a specially designed patch, was used on
      superficial skin cancers and Bowen's disease for local irradiation. METHODS: Ten
      mice with chemically induced skin tumors were studied. Five-millimeter size
      patches containing 22.2-72.15 MBq (0.6-1.95 mCi) 166Ho were applied to the tumor
      surface for 1-2 hr. In a human trial, patients with squamous-cell carcinoma (n =
      3), basal cell carcinoma (n = 1) and Bowen's disease (n = 1) were treated with
      patches containing 273.8-999 MBq (7.4-27 mCi) of 166Ho for 30 min to 1 hr.
      Pathologic examination was performed 4-7 wk after treatment in an animal model.
      Skin biopsy was performed 8 wk post-treatment in four patients. RESULTS: Tumor
      destruction was seen 1 wk post-treatment, however, radiation dermatitis or
      ulceration developed at the site of radionuclide application. Those reactions
      healed gradually with fibrosis or epithelialization, which was confirmed
      pathologically. No significant adverse reaction to radiation except subcutaneous
      fibrosis was found. CONCLUSION: Superficial skin tumors could be successfully
      treated by topical application of beta-emitting radionuclides.

PMID- 9170431
TI  - Clinical decision making based on radionuclide determined ejection fraction in
      oncology patients.
AB  - Decreased left ventricular ejection fraction (LVEF) is a relative
      contraindication for the use of potentially cardiotoxic chemotherapy. A resting
      LVEF of 50% is usually used as the lower limit of normal values. The decision to
      change chemotherapy, however, is complex and is affected by many factors,
      including ejection fraction. METHODS: To determine how LVEF data were used by
      clinical oncologists in clinical decision making, we performed a retrospective
      analysis of patients referred for ejection fraction measurements from the
      hematology/oncology divisionS of Stanford University from March 1992 through
      March 1995. The records of 565 patients treated with potentially cardiotoxic
      chemotherapy were evaluated. RESULTS: LVEFs < 50% were found in 153 patients. The
      charts of patients with reduced ejection fractions were reviewed to determine if
      the radionuclide measurement resulted in either discontinuation of the
      cardiotoxic agent or substitution of a less cardiotoxic drug or mode of
      administration. These specific changes in therapy occurred in only 43 of the 153
      (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection
      fractions < or = 40%. Patients with lower ejection fraction values were more
      likely to have their therapy changed than those with LVEFs close to normal.
      Patients with ejection fractions < or = 30 generally had cardiotoxic agents
      discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not
      changed, 81% had a normal increase in LVEF with exercise. CONCLUSION: In clinical
      practice at our institution, ejection fraction < 50% is not used as an absolute
      contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%,
      potentially cardiotoxic therapy is most often discontinued or omitted.
      Radionuclide evidence of cardiac reserve may account for decisions to continue
      cardiotoxic agents despite ejection fractions < 50% in the majority of patients.
      Further study will be needed to establish standard criteria. Reserve function, as
      measured by the change in ejection fraction from rest to stress may be an
      important parameter used by oncologists to help select patients for continued
      therapy in spite of a reduced ejection fraction. Our results argue that use of
      fixed criteria may be too restrictive.

PMID- 9170432
TI  - Localization of parathyroid glands using technetium-99m-tetrofosmin imaging.
AB  - Preoperative localization of hyperactive parathyroid glands is useful to minimize
      operative time and reduce patient morbidity. This investigation compared the
      sensitivity of radionuclide imaging with 99mTc tetrofosmin with that of
      ultrasonography and magnetic resonance (MR) imaging in patients with
      hyperparathyroidism. METHODS: Twenty-six patients with primary (n = 7) or
      secondary (n = 19) hyperparathyroidism were imaged with 99mTc tetrofosmin,
      ultrasound and MR imaging of the neck and thorax to localize the lesions. The
      presence of hyperparathyroidism was identified by an intact parathyroid hormone
      in vitro assay. The parathyroid/normal thyroid tissue activity ratio was
      calculated for all patients with evidence of an abnormality on tetrofosmin
      images. Pathological findings were compared with the results of imaging in 18 of
      the 26 patients who underwent parathyroidectomy. RESULTS: Technetium-99m
      tetrofosmin scans demonstrated focal uptake in 46 glands of 26 patients. The
      uptake was categorized as slight in 78.3% (36/46) and intense (parathyroid/normal
      thyroid tissue activity ratio, > 1.4) in 21.7% (10/46). Ultrasonography and MR
      imaging identified 44 and 47 glands, respectively, in these patients. Eleven of
      the 18 patients who underwent parathyroidectomy within 1 mo after tetrofosmin
      imaging had hyperplastic glands, while 7 had parathyroid adenomas. Tetrofosmin
      imaging successfully localized 7 of 7 (100%) adenomas and 27 of 37 (73.0%)
      hyperplastic glands. The sensitivities of each technique for localizing abnormal
      parathyroid glands were 77.3% (34/44) for tetrofosmin imaging: 68.2% (20/44) for
      ultrasonography: and 68.2% (30/44) for MR imaging. Technetium-99m tetrofosmin
      uptake ratio in the 18 patients with surgical exploration was not proportional to
      several oxyphil cells. CONCLUSION: Technetium-99m tetrofosmin parathyroid imaging
      may be useful for localizing abnormal glands in patients with primary and
      secondary hyperparathyroidism. The sensitivity of 99mTc tetrofosmin parathyroid
      imaging was high as compared to ultrasonography or MR imaging. The prolonged
      retention of tetrofosmin may not depend on the number of mitochondria-rich
      oxyphil cells.

PMID- 9170433
TI  - Characterizing an ectopic secreting carcinoid with indium-111-DTPA-D-Phe
      pentetreotide.
AB  - This report describes a technique that increases the specificity of 111In
      pentetreotide as evaluated in a patient with ectopic Cushing syndrome. METHODS:
      Two separate SPECT studies were performed with different pharmacologic protocols,
      both including treatment with cold octreotide. The imaging protocol provides
      acquisitions at 4 and 24 hr after injection. The quantitative approach was based
      on the ROI activity (manually designed) of an area of pathological lung uptake
      (ROI-T) versus background (ROI-NT). Histological, histochemical and specific mRNA
      measurements confirmed the presence of an SSR2 receptor carcinoid in the lung.
      RESULTS: The time course of ROI-T/ROI-NT is a linear increase between 4 and 24
      hr. Washout with cold octreotide diminished the ROI-T activity content and the
      saturation protocol increased ROI-T/ROI-NT, confirming the specific nature of the
      uptake. CONCLUSION: Displacement and saturation protocols in 111In-pentetreotide
      imaging demonstrated the specificity of tumor binding.

PMID- 9170434
TI  - Influence of chemotherapy on FDG uptake by human cancer xenografts in nude mice.
AB  - This study evaluated the use of PET with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG)
      for monitoring chemotherapy effects, using a human cancer xenograft (poorly
      differentiated human gastric cancer) in vivo model. METHODS: Tumor 18F-FDG
      uptakes and sizes were measured after administrating mitomycin (MMC), cisplatin
      (CDDP) and adriamycin (ADR) to xenograft-bearing nude mice and compared with 18F
      FDG tumor uptake and tumor size in a non-therapy group. The correlation between
      the uptake and size was also assessed. RESULTS: The largest reduction in tumor
      size after chemotherapy occurred in the MMC administered group, followed by the
      CDDP case, with no reduction in the ADR group as compared to the controls.
      Fluorine-18-FDG tumor uptake after chemotherapy was also decreased in the MMC and
      CDDP groups, in that order, but not in the ADR case. With MMC and CDDP, size
      reduction became significant on Days 8 or 11, whereas 18F-FDG tumor uptake had
      already been decreased on Days 3 or 7. CONCLUSION: Fluorine-18-FDG uptake
      decreases in parallel to the efficacy of anticancer agents and correlates with
      subsequent morphologic changes. We conclude that 18F-FDG PET tumor images are
      indeed useful for monitoring the effects of cancer chemotherapy.

PMID- 9170435
TI  - Transcobalamin II receptor imaging via radiolabeled diethylene
      triaminepentaacetate cobalamin analogs.
AB  - Rapidly dividing cells up-regulate the number of transcobalamin II receptors
      during DNA replication. We have developed diethylene-triaminepentaacetate (DTPA)
      cobalamin analogs for the purpose of imaging transcobalamin II receptors in
      malignant and nonmalignant tissue. METHODS: Methyl-, adenosyl- and cyanocobalamin
      b-(4-aminobutyl)-amide-DTPA analogs were synthesized. In vitro binding of the
      analogs to the transcobalamin proteins was assessed by the unsaturated vitamin
      B12 binding capacity assay and compared to DTPA and cyanocobalamin. The
      biodistribution of the 111In-DTPA cobalamin analogs was measured at 24 hr after
      injection into sarcoma-bearing mice and non-tumor-bearing mice and pigs. RESULTS:
      Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs and
      DTPA were 94.0%, 90.4%, 66.4%, and 3.6%, respectively, as efficient in binding to
      the transcobalamin proteins when compared to cyanocobalamin. At 24 hr after
      administration, the cobalamin analogs had 5-17 times and 20-29 times,
      respectively, the amount of uptake within the resected tissue samples and
      transplanted sarcomas when compared to 111In-DTPA. CONCLUSION: The radiolabeled
      DTPA cobalamin analogs are biologically active. Preliminary animal studies
      suggest that the analogs could be effective in vivo transcobalamin II receptor
      imaging agents.

PMID- 9170436
TI  - Radioassay of yttrium-90 radiation using the radionuclide dose calibrator.
AB  - Yttrium-90 is used in radioimmunotherapy because of its favorable physical half
      life and energetic pure beta emissions. However, it is often necessary to
      standardize 90Y sources to establish a dose calibrator dial setting for accurate
      calibration of clinical doses of 90Y preparations. METHODS: A solution of 90YCl3
      containing 2.81 kBq/ml (by supplier's calibration) was prepared by serial
      dilution In 0.05 M HCl. Ten 100-microliters aliquots of this solution were
      counted in a Packard liquid scintillation analyzer; the mean radioactivity in
      becquerels was determined and used to evaluate dial settings 48 x 10,775 x 70 and
      775 x 100 on a radionuclide dose calibrator for 90Y measurements. The dose
      calibrator response was also studied on 90Y sources at varying solution volumes
      in plastic and glass containers. RESULTS: Calibrator readings of 90Y sources in
      glass and plastic vials and plastic syringes were accurate at either dial setting
      48 x 10 (commonly used by many 90Y laboratories) or 775 x 70. Measurements of
      1.15 and 3.03 GBq (31 and 82 mCi, respectively) calibrated 90Y sources in either
      vial were -3.0 and +4.3%, respectively, at dial-setting 775 x 70 and -4.0 and
      +9.0% at 48 x 10. Yttrium-90 sources in plastic syringes gave higher readings
      than those in glass vials, therefore, requiring a container correction factor for
      accurate dose assay. Measurements of 90YCl3 shipments from four suppliers over a
      3-yr period demonstrated concurring calibration measurements at both 775 x 70 and
      48 x 10 settings for shipments from all suppliers. The dose calibrator response
      to 90Y radiation was linear within a 1-333 kBq range in a constant sample volume
      of 580 microliters. CONCLUSION: This work demonstrates the validity of using the
      48 x 10 dial-factor combination on the standard radionuclide dose calibrator for
      calibration of 90Y radiopharmaceuticals.

PMID- 9170437
TI  - Design and performance characteristics of an experimental cesium-137 irradiator
      to simulate internal radionuclide dose rate patterns.
AB  - When radionuclides are administered internally, the biological effect can depend
      on the total absorbed dose and the rate at which it is delivered. A 137Cs
      irradiator was designed to deliver dose-rate patterns that simulate those
      encountered in radionuclide therapy. METHODS: An 18-Ci 137Cs irradiator was
      fitted with a computer-controlled mercury attenuator that facilitated changes in
      dose rates as desired. The absorbed dose and dose rates were calibrated with
      MOSFET dosimeters customized for low dose-rates. RESULTS: Initial dose rates
      ranging from 0.01-30 cGy/hr can be delivered depending on the location of the
      cage in the irradiator and the thickness of the mercury in the attenuator system.
      To demonstrate the irradiator system's capability to deliver dose-rate patterns
      encountered in radionuclide therapy, a simulation was performed where the dose
      rate initially increased exponentially followed by an exponential decrease in the
      dose rate. CONCLUSION: The irradiator system is well-suited to expose small
      animals to any dose-rate pattern, thereby facilitating calibration of biological
      dosimeters (e.g., cell survival, chromosome aberrations), which can be used to
      measure the absorbed dose to a target tissue after administration of
      radionuclides.

PMID- 9170438
TI  - Potential and limitations of radioimmunodetection and radioimmunotherapy with
      monoclonal antibodies.
AB  - Recently, we developed a physiologically based pharmacokinetic model capable of
      predicting antibody biodistribution in humans by scaling up from mice. By
      applying this model to anticarcinoembryonic antigen murine antibody ZCE025, we
      address several critical issues in radioimmunodetection and radioimmunotherapy,
      including the optimal antibody doses, the desirable antibody form for cancer
      detection, the optimal combinations of antibody forms and radionuclides for
      cancer treatment and the effectiveness of the modality. METHODS: Under the
      baseline conditions of a standard 70-kg man with a 20-g tumor embedded in the
      liver, the model was used to: (a) estimate absorbed doses in tumor and normal
      tissues, (b) determine dose-dependent antibody uptake in the tumor, (c) simulate
      tumor-to-background antibody concentration ratio and (d) calculate therapeutic
      ratios for different antibody forms and radionuclides. Sensitivity analysis
      further enabled us to determine antibody delivery barriers and to assess the
      modality under average and favorable tumor physiological conditions. RESULTS: By
      using ZCE025 under the baseline conditions, the model found that Fab was the most
      suitable form for cancer diagnosis, while 131l combined with F(ab')2 provided the
      highest tumor-to-bone marrow therapeutic ratio for cancer treatment. Sensitivity
      analysis showed that antibody permeability was the major barrier for antibody
      accretion in tumors. It also demonstrated that normal tissue antigen expression
      at a level lower than in the tumor had little effect on the therapeutic ratio.
      CONCLUSION: The model demonstrates that: (a) for radioimmunodetection, the most
      effective antibody form (Fab for ZCE025) was the lower mol weight form, yet not
      sensitive enough for hepatic metastasis detection; and (b) for
      radioimmunotherapy, a relatively fast-clearing antibody form (F(ab')2 for ZCE025)
      in combination with long half-life beta(-)-emitters was optimal, yet inadequate
      as the sole therapeutic modality for solid tumors.

PMID- 9170439
TI  - Effect of myocardial viability assessed by technetium-99m-sestamibi SPECT and
      fluorine-18-FDG PET on clinical outcome in coronary artery disease.
AB  - PET imaging of myocardial perfusion and metabolism identifies regional viability
      as well as patients at high risk for future cardiac events. This study evaluated
      a combined "hybrid" imaging approach using 99mTc-sestamibi SPECT and [18F]fluoro
      2-deoxy-D-glucose (FDG) PET with regard to reversibility of regional dysfunction
      and to patient clinical outcome during a 2-yr follow-up. METHODS: In this study,
      161 consecutive patients underwent baseline viability imaging. All had regional
      wall motion (RWM) abnormalities and 88% had a history of previous myocardial
      infarction. Regions were classified by semiquantitative analysis of sestamibi and
      FDG uptake as normal, mild match, mismatch or scar. For clinical outcome,
      patients were divided into three groups: predominantly scar tissue (Group A, n =
      90), mild match (Group B, n = 26) and mismatch (Group C, n = 45). Treatment was
      performed with the knowledge of nuclear results. Cardiac events during follow-up
      were defined as death, myocardial infarction, unstable angina requiring
      revascularization, heart transplantation and survived resuscitation. RESULTS:
      Patients were followed for 29 +/- 6 mo. Revascularization rate was 30% in Group
      A, 81% in Group B and 80% in Group C, whereas the other patients were treated by
      medication. Only Group C demonstrated a significant reduction of cardiac events
      after revascularization, whereas, particularly in Group A, revascularization did
      not influence the frequency of events. Subjective assessment of angina pectoris
      and heart failure revealed more patients with improvement after revascularization
      as compared with conservative treatment. Of the 84 revascularized patients, 61
      underwent follow-up angiography at 5 +/- 2 mo with RWM analysis using the
      centerline method. RWM improved only in mismatch regions from -2.2 +/- 1.0 s.d.
      to -1.0 +/- 1.4 s.d. (p < 0.01), whereas regions with a mild match or scar did
      not change. CONCLUSION: Nuclear imaging using 99mTc-sestamibi SPECT and [18F]FDG
      PET allows diagnosis of viability in regions with reduced perfusion and function
      with prognostic implications for functional outcome as well as for identification
      of patients who benefit most from revascularization.

PMID- 9170440
TI  - Quantitative LVEF and qualitative regional function from gated thallium-201
      perfusion SPECT.
AB  - This study investigates the feasibility of routine clinical 201Tl gated perfusion
      SPECT (gated Tl), and compares quantitative left ventricular ejection fraction
      (LVEF) and visually-assessed regional wall motion and thickening to analogous
      values obtained from 99mTc-sestamibi gated perfusion SPECT (gated MIBI). METHODS:
      We studied 121 patients with a rest gated Tl (3-3.5 mCi, 35 sec/
      projection/poststress gated MIBI (25-30 mCi, 25 sec/projection) separate dual
      isotope protocol on a 90 degrees dual-detector camera. Automatic quantitation of
      LVEFs was accomplished using previously developed and validated software, while
      visual scoring of motion and thickening was performed using four-point scales.
      RESULTS: Average myocardial counts were lower in gated Tl images (306 +/- 81
      counts/pixel) compared to gated MIBI images (789 +/- 237 counts/pixel). The
      quality of gated Tl images was ranked as excellent, good, fair and poor in 24.0%,
      42.1%, 24.8% and 9.1%, respectively, of the patients, compared to 43.0%, 43.8%,
      9.1% and 4.1%, respectively, for gated MIBI images. Quantitative-gated Tl and
      gated MIBI LVEFs correlated well (y = 0.11 + 1.05x, r = 0.918, SEE = 6.35).
      Possible poststress myocardial stunning may have caused gated Tl LVEFs to
      overestimate gated MIBI LVEFs by a larger (p = 0.03) amount in ischemic patients
      (n = 47, y = -0.69 + 1.09x, r = 0.914, s.e.e. = 6.44) compared to nonischemic
      patients (n = 64, y = -1.58 + 1.05x, r = 0.919, s.e.e. = 5.93), the residual
      difference in LVEFs for this latter group being likely due to different isotope
      resolution in conjunction with small left ventricles. Exact agreement between
      gated Tl and gated MIBI segmental myocardial function in 41 nonischemic patients
      was 92.2% (kappa = 0.619) and 95.4% (kappa = 0.586) for motion and thickening
      scores, respectively. CONCLUSION: Thallium-201 gated SPECT imaging can be
      effectively performed on the majority of patients in our clinical environment and
      offers the opportunity to assess both myocardial perfusion and function using one
      injection and one imaging sequence, similarly to what is done with 99mTc-based
      agents.

PMID- 9170441
TI  - Comparison of SPECT and ectomography for evaluating myocardial perfusion with
      technetium-99m-sestamibi.
AB  - This study compared myocardial perfusion scintigraphy performed with ectomography
      to corresponding SPECT studies. METHODS: In a comparative study between SPECT and
      ectomography, 19 patients with suspected coronary artery disease were imaged
      under similar conditions. A two-day protocol using 99mTc-sestamibi was followed.
      In SPECT, 32 projection images were acquired by rotating the gamma camera
      detector through 180 degrees, from 45 degrees left posterior oblique to 45
      degrees right anterior oblique. Short-axis view sections and polar tomograms were
      reconstructed. In ectomography, a 30 degrees slant-hole collimator was rotated
      through 360 degrees in front of a stationary detector to obtain 64 projection
      images with different projection directions. The gamma camera was orientated
      perpendicular to the long axis of the left ventricle; the orientation was
      determined from the SPECT examination. Short-axis section images through the
      projected conical volume were reconstructed using a two-dimensional filtered back
      projection technique. In a blind test, the relative diagnostic value and image
      quality of the two methods were evaluated by three independent observers
      assessing short-axis view sections and polar tomograms. An objective evaluation
      based on relative values in the polar tomograms was also performed. The
      interpretations were evaluated with analysis of variance. RESULTS: After
      injection during exercise, there was no significant difference between SPECT and
      ectomography. After injection at rest, visualization of the left ventricle was
      superior (p < 0.05) and influence of external activity was less (p < 0.005) in
      ectomography. The activity level within a perfusion defect was significantly
      lower (p < 0.05) and its extension significantly larger (p < 0.05) in
      ectomography than in SPECT. There was no difference between the diagnosis based
      on SPECT or ectomography. CONCLUSION: In myocardial perfusion imaging with 99mTc
      sestamibi, ectomography provides information similar to that obtained with SPECT
      and can, therefore, be used clinically for evaluation of myocardial perfusion
      when the gamma camera is postitioned perpendicular to the long axis of the left
      ventricle.

PMID- 9170442
TI  - Progressive heterogeneity of myocardial perfusion in heart transplant recipients
      detected by thallium-201 myocardial SPECT.
AB  - Progressive graft atherosclerosis is a serious complication in long-term
      survivors after heart transplantation. Coronary angiography is insensitive with
      regard to the early and characteristic alterations. We evaluated the progression
      of these abnormalities and the influence of former rejection episodes. METHODS:
      Early after transplantation, 43 patients (34 men, mean age 53.7 +/- 10.7 yr)
      underwent stress and redistribution 201Tl myocardial SPECT after treadmill
      exercise. Twenty patients were followed-up to the second postoperative year, and
      13 patients to the third postoperative year. Thallium-201 distribution and
      kinetic abnormalities were documented in a scheme enclosing 20 myocardial
      segments. Additionally, a score was developed that measured the degree of
      inhomogeneity of 201Tl distribution and the severity of perfusion defects,
      respectively. RESULTS: Regarding scintigraphy, pathologic results could be found
      in 40% of segments (redistribution, 25%; reverse redistribution, 30%; persistent
      defects, 49%). Score values in heart transplant recipients differed significantly
      from normal controls (p < 0.001) and were comparable to patients with single
      vessel disease of their native hearts. Thallium-201 inhomogeneity in recipients
      after treatable rejection episodes did not differ from results in recipients
      without any biopsy-proven rejection. The follow-up of cardiac transplant patients
      revealed a significant increase of score values up to the third year after
      transplantation (p < 0.02), despite reproducible normal angiography. There was no
      direct correlation between score values and IVUS results, although there was a
      parallel trend in 10 of 12 follow-ups. CONCLUSION: Despite normal coronary
      angiography, 201Tl myocardial SPECT frequently revealed pathologic results in
      heart transplant recipients. Scintigraphic results did not correlate with intimal
      thickening of epicardial coronary arteries accessible to intravascular
      ultrasonography in the early phase after transplantation. The presented score of
      inhomogeneity might reveal progressive disease possibly caused by small vessel
      alterations.

PMID- 9170443
TI  - Left ventricular cavity-to-myocardium count ratio in technetium-99m-sestamibi
      SPECT in the detection of resting left ventricular dysfunction.
AB  - The aim of this study was to assess the value of the cavity-to-myocardium count
      ratio (C/M ratio) calculated in resting 99mTc-sestamibi SPECT images to identify
      patients with depressed left ventricular ejection fraction (LVEF). METHODS: In
      the 95 patients studied, the C/M ratio was calculated from the midventricular
      short-axis slice using regions of interest drawn in the center of the cavity and
      in the most active area of the ventricular wall; its value was compared with LVEF
      measured using two-dimensional echocardiography. RESULTS: The C/M ratio
      correlated with LVEF (r = 0.6, p < 0.000001) and was significantly lower in
      patients with abnormal LVEF than those with normal LVEF: 0.026 +/- 0.028 versus
      0.125 +/- 0.093, p < 0.000001. In the entire patient population, a C/M ratio <
      0.07 identified the patients with depressed LVEF with a 94% sensitivity, 71%
      specificity and 82% accuracy. CONCLUSION: The resting 99mTc-sestamibi C/M ratio
      is a useful parameter in identifying patients with depressed LVEF directly from
      the SPECT perfusion images.

PMID- 9170444
TI  - PET perfusion and vasodilator function after angioplasty for acute myocardial
      infarction.
AB  - The aims of this study were to validate invasive coronary Doppler flows against
      noninvasive PET assessments of myocardial perfusion and to examine the timing and
      degree of regional coronary vasodilator reserve recovery in patients who are
      successfully reperfused with primary angioplasty (PTCA) for acute myocardial
      infarction. METHODS: PTCA was performed in 21 consecutive patients with acute
      myocardial infarction; the final diameter stenosis was 25% +/- 7%. After
      restoration of TIMI Grade 3 flow, all patients underwent quantitative coronary
      angiography and distal Doppler coronary blood flow studies (basal and after
      adenosine-induced hyperemia) in the infarct and noninfarct vessels. Regional
      myocardial perfusion and vasodilator function were quantitated after intravenous
      adenosine infusion PET in all patients at 26 +/- 9 hr after acute PTCA. These
      were repeated in 17 patients 9 +/- 3 days later. RESULTS: Post-PTCA resting
      coronary flow was 35 +/- 15 ml/min in the infarct-related vessels and 50 +/- 24
      ml/min during peak hyperemia (p < 0.05). Coronary flow reserve (CFR) was 1.48 +/-
      0.34 and 2.08 +/- 0.62 in the infarct and noninfarct vessels, respectively (p <
      0.001). Early (< 36 hr) PET myocardial perfusion reserves (MPR) in the infarct
      and noninfarct regions were 1.59 +/- 0.33 and 2.03 +/- 0.62 (p < 0.01). Doppler
      CFR and PET MPR were correlated in the infarct (r = 0.61, p < 0.01) and
      noninfarct (r = 0.77, p < 0.0001) regions. Follow-up PET studies demonstrated
      improved MPR in both infarct and noninfarct regions (1.93 +/- 0.52 versus 2.54 +/
      0.97, p < 0.01). The improvement in coronary vasodilator function from the time
      of acute PTCA to follow-up PET in the infarct region was significant (p = 0.005).
      CONCLUSION: After successful mechanical revascularization by PTCA after acute
      myocardial infarction, intracoronary Doppler blood flows and noninvasive PET
      regional myocardial perfusion are correlated within the wide range of reperfusion
      blood flows observed in patients with contrast angiographic TIMI Grade 3 flow.
      Serial PET studies demonstrated a trend towards continued improvement in the
      vasodilator response in infarct-related myocardial regions after the restoration
      of blood flow by PTCA. PET offers the potential for accurate noninvasive serial
      assessment of reperfusion blood flow after primary angioplasty for acute
      myocardial infarction.

PMID- 9170445
TI  - Severe right ventricular contraction asynchronism revealing a large pericardial
      effusion.
AB  - A gated blood-pool equilibrium radionuclide angiography was performed in a
      patient to determine the ejection fraction for doxorubicin cardiotoxicity
      evaluation. The phase image of the first harmonic of the Fourier analysis
      revealed a severe delay of the right ventricular contraction compared with that
      of the left ventricle. This right ventricular contraction asynchronism was due to
      a large pericardial effusion, confirmed by the presence of the halo sign on the
      summed gated images and by echocardiography. The phase delay moves towards
      normalization after pericardiocentesis. Although radionuclide angiocardiography
      is not the best method for identification of pericardial effusion, this diagnosis
      should be evoked when a severe homogenous delay of the right ventricular
      contraction is observed.

PMID- 9170447
TI  - Comparison of motion correction algorithms for cardiac SPECT.
AB  - Patient motion remains a significant source of unsatisfactory cardiac SPECT
      examinations. The extent to which image recovery can be achieved with correction
      algorithms is unknown. METHODS: Nine subjects who had completed motion-free
      redistribution 201Tlcardiac SPECT subsequently underwent simultaneous dual
      isotope (201Tl/99mTc) SPECT with a 99mTc cutaneous point source, while the
      imaging table was subjected to predefined nonreturning y-translation movements.
      Cardiac reconstructions, marker reconstructions and marker-compressed dynamic
      images were generated from the raw data after applying the following correction
      methods: diverging squares, cross-correlation of the cardiac data and cross
      correlation of the marker. RESULTS: Marker cross-correlation performed
      significantly better than all other methods with good-excellent results in all
      evaluations. This compared with good-excellent results in none of 27 for the raw
      data, in 13 of 27 for cardiac cross-correlation and in 7 of 27 for diverging
      squares (p < 10(-5)). The superiority of the marker-based method was confirmed on
      analysis of bullseye difference maps and quantitation of residual motion in the
      point-source data. CONCLUSION: Motion artifacts can accurately be detected and
      corrected using cross-correlation of an external point-source. Furthermore, this
      technique provides useful independent information on the degree of image
      recovery.

PMID- 9170446
TI  - Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart.
AB  - The kinetics of EPI were studied in the isolated rat heart model to evaluate 11C
      epinephrine (EPI) as a radiotracer for the assessment of sympathetic neuronal
      function in the heart. METHODS: Isolated rat hearts were perfused in a working
      mode. Carbon-11-EPI was added to the perfusate during wash-in period of 20 min,
      followed by a washout period of 40 min. Radioactivity in the heart was externally
      monitored and time-activity curves were recorded as a function of time. Effluent
      samples were collected throughout each study to determine the fraction of 11C
      radioactivity as intact tracer. RESULTS: Time-activity curves of control hearts
      showed that 11C-EPI is taken up and retained by the myocardium. Desipramine
      inhibition (DMI) of uptake-1 resulted in a significant decrease in myocardial
      uptake and retention of 11C-EPI by 91% compared to controls. Addition of DMI to
      the perfusion medium during washout did not affect kinetics of 11C-EPI compared
      to control hearts. Reserpine pretreated rat hearts also showed significant
      decrease in tracer retention of 95% compared to controls. The metabolic data
      showed that, in control conditions, about 61% of 11C-EPI taken up by the rat
      heart is rapidly metabolized and released. CONCLUSION: Carbon-11-EPI traces
      sympathetic nerve terminals in the isolated rat heart. Uptake blockade by DMI and
      reserpine suggest that uptake and storage of 11C-EPI appear to be similar to that
      of norepinephrine. However, the prominent metabolic pathway warrants further
      consideration. These results suggest that 11C-EPI may be a suitable radiolabeled
      tracer for the evaluation of sympathetic vesicular function of the heart by PET.

PMID- 9170448
TI  - Technetium-99m-ECD brain SPECT in misery perfusion.
AB  - Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain
      distribution have been reported when brain tissue is supplied by excess blood
      flow. We evaluated changes in 99mTc-ECD brain activity in the opposing
      pathological state, in which cerebral blood flow (CBF) is more profoundly
      impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity
      with CBF and metabolism to investigate the dominant regulating factor on 99mTc
      ECD distribution. METHODS: Twelve patients with unilateral intracranial steno
      occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT.
      Relative 99mTc-ECD activities and the retention ratio of the affected and
      unaffected cortices were compared with CBF and oxygen metabolism obtained by PET.
      Change in the relationships until 1 hr after tracer injection were also analyzed.
      RESULTS: Relative 99mTc-ECD activity was significantly correlated with CBF, and
      the highest correlation was obtained for the first minute of imaging (r = 0.674,
      p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF
      decreased, whereas higher correlation was observed with the parameter of oxygen
      metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were
      dependent on changes in oxygen metabolism, and the retention ratio for the high
      oxygen extraction fraction (OEF) area was the same as that for the normal OEF
      area. CONCLUSION: In addition to CBF, brain distribution on 99mTc-ECD SPECT
      images is affected by brain metabolism, especially on delayed images after
      injection. The degree of discrepancy between CBF and metabolism should be
      considered when interpreting images of the misery perfusion state.

PMID- 9170449
TI  - Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched
      for dementia severity.
AB  - Despite controversial clinicopathological distinctions between Parkinson's
      disease with dementia (PDD) and Alzheimer's disease (AD), similar patterns of
      metabolic reduction in the posterior brain were reported previously using PET
      with [18F]fluorodeoxyglucose. The current study was designed to examine more
      specific regional differences in cerebral glucose metabolism between PDD and AD
      using accurate and objective brain mapping techniques. METHODS: This study
      included nine normal subjects, nine PDD patients and nine AD patients. PDD and AD
      groups were matched carefully for age, sex and general dementia severity as
      measured by Mini-Mental State Examination and Clinical Dementia Rating scales.
      Each subject underwent [18F]fluorodeoxyglucose-PET and neuropsychological
      testing. After anatomic standardization of PET image sets and stereotactic data
      extraction, absolute and normalized cerebral metabolic rates were assessed by
      region of interest and pixel-by-pixel analyses. RESULTS: PDD and AD showed global
      glucose metabolic reduction with similar regional accentuation involving the
      lateral parietal, lateral temporal and lateral frontal association cortices and
      posterior cingulate cortex in comparison to normal controls. When comparing
      between PDD and AD, however, PDD showed greater metabolic reduction in the visual
      cortex and relatively preserved metabolism in the medial temporal cortex.
      CONCLUSION: Although a common feature of metabolic abnormalities in the posterior
      brain exists in PDD and AD, the presence of regional metabolic differences
      suggests different degrees and combinations of disease specific underlying
      pathological and neurochemical processes.

PMID- 9170450
TI  - Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors.
AB  - The high glucose utilization of normal gray matter limits the detection of brain
      tumor tissue by PET using 18F-fluorodeoxyglucose (FDG). The aim of this study was
      to evaluate whether the examination of amino acid transport with the SPECT tracer
      123l-alpha-methyl-L-tyrosine (IMT) allows better identification of tumor tissue
      than FDG-PET. METHODS: Nineteen patients (16 with gliomas, 3 with nontumorous
      lesions) were included in the study. Two independent observers classified PET and
      SPECT images as positive or negative for tumor tissue and defined the extent of
      tumor with regions of interest. Tracer uptake of FDG and IMT was quantified by
      calculating the tumor uptake relative to contralateral gray and white matter.
      RESULTS: SPECT studies were interpreted concordantly in 18 patients (kappa =
      0.77) and all tumors were identified by both observers. PET studies were
      interpreted discordantly in 4 patients (kappa = 0.52) and only 10 tumors were
      identified by both observers, interobserver variability in definition of tumor
      extent was significantly lower in the IMT-SPECT than in the FDG-PET studies (p =
      0.03). Mean tumor uptake relative to gray and white matter was 1.93 +/- 0.42 and
      2.25 +/- 0.46 for IMT and 0.93 +/- 0.32 and 1.61 +/- 0.52 for FDG. All tumor
      uptake ratios were significantly (p < 0.01) higher for IMT than FDG, even when
      only glioblastomas were analyzed. No significant correlation was observed between
      the various uptake ratios of FDG and IMT. CONCLUSION: Despite the lower
      resolution and lower sensitivity of SPECT compared with PET, IMT-SPECT was
      clearly superior to FDG-PET in the detection and delineation of tumor tissue.

PMID- 9170451
TI  - Clinical evaluation of technetium-99m-L,L-ethylenedicysteine in patients with
      chronic renal failure.
AB  - Technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC), a new renal
      radiopharmaceutical, has been shown to have similar excretion characteristics but
      a higher plasma clearance than 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) in
      normal volunteers and patients with obstructive nephropathy. This study evaluated
      99mTc-L,L-EC in patients with chronic renal failure. METHODS: The clearance of
      99mTc-L,L-EC was compared with that of 125l-hippuran in 26 patients with varying
      degrees of chronic renal impairment (serum creatine 168-1163 mumol/liter). All 26
      patients also were imaged with 99mTc-L,L-EC (70-80 MBq). Fifteen patients had
      further imaging with 99mTc-MAG3 (100 MBq) the following day. RESULTS: A
      subjective analysis of the 99mTc-L,L-EC images revealed that all were of
      acceptable quality regardless of creatinine level. In the 15 patients who were
      imaged with both 99mTc-L,L-EC and 99mTc-MAG3, general image quality and target-to
      background ratios were similar. Time-activity curves and mean parenchymal transit
      times obtained with the two agents were almost identical. Plasma clearance values
      (mean +/- s.d.) of 99mTc-L,L-EC and 125l-hippuran were 81 +/- 68 ml/min and 114
      +/- 104 ml/min, respectively. Mean 99mTc-L,L-EC clearance was 71% of the mean
      125l-hippuran value. CONCLUSION: Technetium-99m-L,L-EC provides equally high
      quality images to 99mTc-MAG3 in patients with chronic renal failure. Technetium
      99m-L,L-EC clearance more closely resembles that of hippuran than does 99mTc-MAG3
      clearance. These features together with its ease of preparation make 99mTc-L,L-EC
      an attractive alternative to 99mTc-MAG3 in patients with chronic renal failure.

PMID- 9170452
TI  - Evidence of accelerated gastric emptying in longstanding diabetic patients after
      ingestion of a semisolid meal.
AB  - This study investigated the prevalence of accelerated gastric emptying in 40
      consecutive nonselected patients with longstanding insulin-dependent diabetes
      mellitus (range 11-54 yr; mean 27 yr). METHODS: The gastric emptying of a
      semisolid meal labeled with 99mTc was continuously recorded with a dual-head
      gamma camera for 90 min in patients who were supine. RESULTS: Eleven patients
      demonstrated delayed gastric emptying, but three male diabetics showed
      accelerated gastric emptying with retention values that were different from
      controls already after 10 min of recording (89% +/- 3% versus 96% +/- 4%; p <
      0.02). During the 90-min segment, accelerated gastric emptying reduced initial
      gastric contents to 11% +/- 8% (p < 0.001) as compared to 50% +/- 10% in control
      subjects and 78% +/- 6% (p < 0.001) in patients with delayed gastric emptyings.
      Accelerated gastric emptying was characterized by an almost equal initial meal
      distribution in proximal and distal compartments of stomach, both emptying
      approximately 90% of their contents within 90 min. Normal and delayed gastric
      emptying was characterized by a 60%-40% initial ratio of meal distribution
      between gastric compartments. During normal emptying, both compartments reduced
      contents with approximately 50%, but delayed gastric emptying was caused by only
      a 15% reduction of proximal contents accompanied by a 34% reduction in distal
      contents. CONCLUSION: Recording in the supine position to abolish gravitational
      influences demonstrated accelerated gastric emptying of a firm semisolid meal
      with a prevalence of 8%. However, delayed gastric emptying was shown as the
      predominant gastric manifestation of longstanding insulin-dependent diabetes
      mellitus with a prevalence of 28%.

PMID- 9170453
TI  - Disseminated islands of gastric mucosa in jejunum and ileum detected by
      technetium-99m-pertechnetate scintigraphy.
AB  - Disseminated islands of gastric mucosa are very rare in the small intestine. The
      secretion of hydrochloric acid can lead to ulceration which results in
      gastrointestinal bleeding. It is often difficult to localize the focus in case of
      gastrointestinal blood loss especially in the small bowel. Technetium-99m
      pertechnetate scintigraphy may be a helpful tool in detecting ectopic gastric
      mucosa. We report a case of a 21-mo-old boy with recurrent gastrointestinal
      bleeding. By using pertechnetate scintigraphy, extensive tracer accumulation in
      the jejunum and proximal ileum was detected. Histologically, multiple islands of
      ectopic gastric mucosa were found in about 50 excited mucosal and transmural
      biopsies. The unusual finding of disseminated accumulation of 99mTc-pertechnetate
      in the small intestine was the diagnostic clue for such a rare disease.

PMID- 9170455
TI  - Somatostatin receptors in schwannomas.

PMID- 9170454
TI  - Comparison of technetium-99m-ll-EC isomers in rats and humans.
AB  - Technetium-99m-L,L-ethylenedicysteine (99mTc-LL-EC) is a new renal imaging agent
      with pharmacokinetic properties reported to be slightly superior to those of
      99mTc-mercaptoacetyltriglycine (99mTc-MAG3); however, to better define the
      potential of the enantiomer 99mTc-DD-EC and the diastereomer 99mTc-DL-EC as renal
      imaging agents, we compared the three EC stereoisomers with 131I
      orthoiodohippurate (OIH) in a series of rats and humans. METHODS: Each 99mTc-EC
      stereoisomer was coinjected with OIH in six Sprague-Dawley rats for measurements
      of clearance and extraction fraction. Each stereoisomer was also coinjected with
      OIH in three human volunteers followed by sequential imaging, plasma clearance
      measurements and timed urine collections. RESULTS: Technetium-99m-DD-EC had the
      highest clearance and extraction efficiency in rats (p < or = 0.02). In humans,
      image quality was good with all three agents. The clearance ratio (EC/OIH) was
      82% +/- 8% for 99mTc-DD-EC compared to 70% +/- 3% and 40% +/- 5% for 99mTc-LL-EC
      and 99mTc-DL-EC, respectively. Technetium-99m-DD and 99mTc-LL-EC were excreted
      more rapidly than 99mTc-DL-EC. CONCLUSION: Technetium-99m-DD-EC has excellent
      imaging properties and the data suggest that its clearance may approach that of
      OIH more closely than any other 99mTc renal agent. A potential limitation is the
      fact that both 99mTc-DD and LL-EC exist in dianionic (80%) and monoanionic (20%)
      forms at physiological pH and it is unlikely that these two forms have the same
      clearance or protein binding affinity.

PMID- 9170456
TI  - Captopril renography in the detection of RVH.

PMID- 9170457
TI  - Discordant uptake of MIBI and HMPAO.

PMID- 9170458
TI  - Evaluating the significance of changes in brain SPECT.

PMID- 9170459
TI  - Intracellular fate of radiometals.

PMID- 9170461
TI  - Anal incontinence after anal sphincter disruption: a 30-year retrospective cohort
      study.
AB  - OBJECTIVE: To compare the prevalence of anal incontinence remote from delivery
      (approximately 30 years postpartum) in 29 women whose index delivery was
      complicated by anal sphincter disruption versus a matched control group of 89
      women who had an episiotomy without extension to the anal sphincter and versus a
      group of 33 women who delivered via cesarean. METHODS: In this retrospective
      cohort study, a structured questionnaire was sent to women in the above
      categories who delivered at a university hospital between 1961 and 1965 and for
      whom we could obtain current addresses. Outcome measures included frequent fecal
      and flatus incontinence and bothersome fecal and flatus incontinence. RESULTS:
      The three groups did not differ significantly in age, weight, age at delivery,
      parity, weight of largest baby, postmenopausal status, estrogen replacement
      usage, most medical conditions, or rectocoele, rectovaginal fistula, or
      incontinence surgeries. Frequent flatus incontinence was reported by nine
      (31.0%), 38 (42.7%), and 12 (36.4%) women in the anal sphincter disruption,
      episiotomy, and cesarean groups, respectively (not significant). The number of
      women with bothersome flatus incontinence was higher in the anal sphincter
      disruption group: 17 (58.6%) versus 27 (30.3%) in the episiotomy only group and
      versus five (15.2%) in the cesarean group (P = .001). Frequent fecal incontinence
      was reported by two (6.9%), 16 (18.0%), and 0 women (P = .008 between cesarean
      and episiotomy only groups), whereas bothersome fecal incontinence was reported
      by eight (27.6%), 23 (25.8%), and five (15.2%) women (not significant) in the
      anal sphincter disruption, episiotomy only, and cesarean groups, respectively.
      CONCLUSION: Regardless of the type of delivery, anal incontinence occurs in a
      surprisingly large number of middle-aged women.

PMID- 9170462
TI  - Pelvimetry by magnetic resonance imaging as a diagnostic tool to evaluate
      dystocia.
AB  - OBJECTIVE: To test the clinical value of magnetic resonance imaging (MRI)
      pelvimetry for the diagnosis of cephalopelvic disproportion. METHODS: All
      deliveries from January 1993 through December 1994 were reviewed to identify 42
      nulliparas at term with vertex presentation and cesarean delivery due to
      dystocia. Complete data were available for 41 women, and subjects were divided
      into the following two subgroups, according to clinical data: "cephalopelvic
      disproportion" (n = 28) and "failure to progress" (n = 13). Ten nulliparous women
      with uncomplicated vaginal delivery served as controls. Pelvimetry data from
      postpartum MRI were correlated with fetal and neonatal dimensions to evaluate
      various criteria for the diagnosis of cephalopelvic disproportion. RESULTS:
      Comparing both the fetal head volume derived from antepartum ultrasound
      assessment and the neonatal head volume (postpartum measurement) with maternal
      pelvic capacity determined by MRI, cephalopelvic disproportion (head volume
      exceeding pelvic capacity) indicated that 25 and 27, respectively, of the 28
      women had been clinically diagnosed correctly with cephalopelvic disproportion,
      corresponding to sensitivities of 89% and 96%, respectively. Fetal head volume
      was not larger than pelvic capacity in any of the women in the control group. In
      seven of the 13 women diagnosed as "failure to progress," the fetal head volume
      exceeded the pelvic capacity. CONCLUSION: A fetal head volume estimate exceeding
      MRI-measured pelvic capacity is a frequent finding in nulliparas with cesarean
      birth due to cephalopelvic disproportion. An appropriate prospective study to
      determine the benefits of an antepartum diagnosis of cephalopelvic disproportion
      in high-risk nulliparas is warranted.

PMID- 9170460
TI  - Genital herpes during pregnancy: inability to distinguish primary and recurrent
      infections clinically.
AB  - OBJECTIVE: To determine if the signs and symptoms of genital herpes in pregnancy
      accurately identify primary genital herpes infections using serologic testing for
      final classification. METHODS: Twenty-three women with clinical signs and
      symptoms suggestive of primary genital herpes infections in the second and third
      trimesters of pregnancy were subsequently cultured and tested serologically (for
      herpes simplex virus type 1 and herpes simplex virus type 2 antibodies) and
      classified as having true primary (no herpes simplex virus type 1 or type 2
      antibodies), nonprimary (heterologous herpes simplex virus antibodies present),
      or recurrent (homologous antibodies present) infections. RESULTS: Only one of 23
      women with clinical illnesses consistent with primary genital herpes virus
      simplex infections had serologically-verified primary infection. This primary
      infection was caused by herpes simplex virus type 1. Three women had nonprimary
      type 2 infections, and 19 women had recurrent infections. Among culture-proven
      recurrent infections, 12 were caused by herpes simplex virus type 2 and three by
      herpes simplex virus type 1. Only one infant was born preterm, and no clinically
      significant perinatal morbidity was observed. CONCLUSION: Correct classification
      of gestational genital herpes infections can be accomplished only when clinical
      evaluation is correlated with viral isolation and serologic testing using a type
      specific assay. Severe first episodes of genital herpes infections among women in
      the second and third trimesters of pregnancy are not usually primary infections
      and are not commonly associated with perinatal morbidity.

PMID- 9170463
TI  - Labor induction with intravaginal misoprostol in term premature rupture of
      membranes: a randomized study.
AB  - OBJECTIVE: To evaluate the safety and clinical effectiveness of intravaginal
      misoprostol, a synthetic prostaglandin E1 analogue, for labor induction in
      gravidas with premature rupture of membranes (PROM) at term. METHODS: One hundred
      forty-one pregnant women with term PROM were assigned randomly to one of two
      induction groups: 1) intravaginal misoprostol or 2) intravenous oxytocin by
      continuous infusion. RESULTS: Seventy subjects were allocated to the misoprostol
      group and 71 to the oxytocin group. The mean (+/- standard deviation) interval
      from induction to delivery was significantly shorter in the misoprostol group
      (416 +/- 276 compared with 539 +/- 372 minutes; P = .04). In 85.7% of patients in
      the misoprostol group, only one dose was required. Intrapartum complication
      rates, mode of delivery, and neonatal or maternal adverse event rates were
      similar in the two treatment groups. Uterine tachysystole occurred more
      frequently with misoprostol than with oxytocin (28.6% compared with 14.0%; P <
      .04). CONCLUSION: Intravaginal administration of misoprostol induces labor safely
      and effectively in patients with PROM at term.

PMID- 9170464
TI  - Induction of labor versus expectant management in macrosomia: a randomized study.
AB  - OBJECTIVE: Macrosomia at term is associated with increased maternal and neonatal
      morbidity, including a higher rate of cesarean delivery and shoulder dystocia.
      Induction of labor has been suggested as a means to prevent further weight gain
      and improve outcome. The aim of this study was to determine whether or not
      induction of labor in these cases improves maternal and neonatal outcome.
      METHODS: Patients at term with an ultrasonic fetal weight estimation of 4000-4500
      g were prospectively randomized into two groups: induction of labor (group D and
      expectant management (group II). Patients with diabetes, a previous cesarean
      delivery, or nonvertex presentation were excluded. Outcome variables included
      mode of delivery, arterial cord pH, presence of shoulder dystocia, brachial
      plexus injury, clavicular fracture, cephalohematoma, and intraventricular
      hemorrhage. RESULTS: Of 273 patients who were eligible for the study, 134 were
      randomized to group I and 139 to group II. Parity, gestational age, and fetal
      weight estimation were similar in the two groups. The neonates of group II
      patients were significantly heavier (4132.8 +/- 347.4 versus 4062.8 +/- 306.9 g;
      P = .024). The rate of cesarean delivery was 19.4% in group I and 21.6% in group
      II patients (not significant [NS]). Cord pH was similar in both groups. Shoulder
      dystocia was diagnosed in five group I and six group II patients (NS). None
      developed brachial plexus injury. There were two cases of mild, transient
      brachial plexus injury in group II patients without documented shoulder dystocia.
      Mild intraventricular hemorrhage was diagnosed in three of 44 group I and two of
      31 group II neonates evaluated (NS). CONCLUSION: In this prospective, randomized
      study, induction of labor for suspected macrosomia at term did not decrease the
      rate of cesarean delivery or reduce neonatal morbidity. Ultrasonic estimation of
      fetal weight between 4000 and 4500 g should not be considered an indication for
      induction of labor.

PMID- 9170465
TI  - Sex steroid receptors and human parturition.
AB  - OBJECTIVE: To investigate the correlation between sex steroid hormones and their
      receptors during normal and dysfunctional labor. METHODS: Myometrial and decidual
      biopsies along with maternal and cord blood samples were taken from women with or
      without labor activity. Estrogen and progesterone receptor contents in myometrium
      and decidua were determined by enzyme immunoassay, and hormone concentrations
      were analyzed by radioimmunoassay. RESULTS: In the lower segment of the uterus,
      the progesterone receptor concentrations of myometrium were significantly lower
      in oxytocin-resistant dystocia compared with those of normal labor and before
      labor (P < .04, P < .005, respectively). No significant difference was found in
      the estrogen receptors contents in the groups studied. The progesterone receptors
      of myometrium from the upper segment showed higher concentrations in active labor
      compared with those before labor and oxytocin-resistant labor (P <.01, P < .05,
      respectively). Estrogen receptors from the upper segment showed no significant
      difference in these regards. There was no difference in peripheral and myometrial
      sex hormone levels in the groups studied. CONCLUSION: These data suggest that, in
      the human, 1) oxytocin-resistant labor is associated with low levels of
      progesterone receptors, 2) estrogen receptors content in myometrium might have no
      or little relation to labor, and 3) functional labor seems not to be related to a
      decreased progesterone activity in the myometrium.

PMID- 9170466
TI  - Cost-minimization analysis of domiciliary antenatal fetal monitoring in high-risk
      pregnancies.
AB  - OBJECTIVE: To compare safety and cost-effectiveness of domiciliary antenatal
      fetal monitoring (cardiotocography and obstetric surveillance) with in-hospital
      monitoring in high-risk pregnancies. METHODS: From September 1992 to June 1994,
      150 consecutive women with high-risk pregnancies, who would otherwise be
      monitored in the hospital, entered a randomized controlled trial of in-hospital
      (n = 74) or domiciliary (n = 76) monitoring. The main outcome measures were
      neonatal safety (Prechtl neurologic optimality score, the proportion of non
      optimals) and cost-effectiveness. To test a two-point difference in mean Prechtl
      scores (two-tailed o = .05. 1-beta = .80), 150 women were needed. Safety and cost
      effectiveness were analyzed according to intention to treat. Conditional on the
      safety outcomes, a cost-minimization analysis based on actual resource use was
      performed. Uncertainty of results was explored by sensitivity analyses. RESULTS:
      Neonatal outcomes were equal. No cost-shifting between the antenatal and
      postpartum period occurred. Substituting domiciliary for in-hospital monitoring
      reduced mean (standard deviation) antenatal costs from $3558 ($2841) to $1521
      ($1459) per woman (P < .001). If costs were varied by the addition of 50%, costs
      were still reduced. The magnitude of the reduction was sensitive to the costs of
      hospital care and less sensitive to the costs of domiciliary monitoring.
      CONCLUSION: Domiciliary monitoring is safe and reduces costs by one-half. The
      technique seems transferable to other settings but local circumstances may
      sometimes hamper its dissemination.

PMID- 9170467
TI  - The effect of early discharge after vaginal delivery on neonatal readmission
      rates.
AB  - OBJECTIVE: To determine the effect of a structured program for early neonatal
      discharge from a tertiary medical center on the risk of neonatal readmission.
      METHODS: An early-discharge program was instituted at our tertiary medical center
      in July 1993, with the objective of discharging mothers and infants within 24
      hours after vaginal birth. The readmission rate of vaginally delivered infants
      during the early-discharge period (July 1, 1993, through March 31, 1995) was
      compared with the rate during a conventional-discharge period (January 1, 1992,
      through June 30, 1993). Analyses were performed to examine two groups within the
      early-discharge group: those discharged within 24 hours of vaginal delivery; and
      those discharged within 1 hospital day of vaginal delivery. RESULTS: During the
      early-discharge period, 1.24% of neonates were readmitted within 10 days of
      birth, compared with 1.35% during the conventional-discharge period. In the early
      discharge period group, infants born vaginally and discharged within 24 hours of
      birth had a readmission rate of 1.46% compared with 1.14% for those who stayed
      longer than 24 hours after delivery. Similarly, the readmission rate was no
      different for infants who were discharged within 1 hospital day. The primary
      indications for readmission in both periods were infections and jaundice.
      CONCLUSION: Implementation of a structured program for early neonatal discharge
      does not have an association with increased risk of neonatal readmission to the
      hospital.

PMID- 9170468
TI  - The predictive value of first-trimester embryonic heart rates in infertility
      patients.
AB  - OBJECTIVE: To analyze whether first-trimester embryonic (fetal) heart rates (FHR)
      are useful in predicting pregnancy outcome for infertility patients. METHODS:
      Patients in a university-based reproductive endocrinology and infertility
      practice were studied prospectively. Infertile women who achieved clinical
      pregnancy underwent first-trimester transvaginal sonographic evaluation, and FHR
      in patients achieving viable pregnancies were compared with those experiencing
      fetal loss. RESULTS: Overall, 99 pregnancies reached viability and 17 resulted in
      fetal loss before 20 weeks' gestation. Patient age, methods of conception, and
      number of previous fetal losses did not differ significantly between the two
      groups. A significant correlation (r = .70, P < .001) was found between
      increasing FHR levels and advancing gestational age in patients with viable
      pregnancies and, although to a weaker extent, patients who miscarried (r= .52, P
      < .05). A significantly higher number of viable pregnancies, compared with fetal
      losses, had FHR falling within one (70.7% compared with 41.2%, P < .025) and two
      (99.0% compared with 64.7%, P < .001) standard deviations of the mean for viable
      pregnancies at corresponding gestational ages. The majority of FHR of failing
      pregnancies fell below the individual reference ranges. CONCLUSION: First
      trimester FHR can help predict pregnancy outcome for infertility patients. Women
      with FHR outside the reference range from the mean for viable pregnancies at
      corresponding gestational ages may be at risk for eventual pregnancy loss.

PMID- 9170469
TI  - Prediction of adverse perinatal outcome by maternal serum screening for Down
      syndrome in an Asian population.
AB  - OBJECTIVE: To investigate the association between adverse perinatal outcomes and
      abnormal elevations of serum marker levels (alpha-fetoprotein [AFP] and free beta
      hCG) or a false-positive screen for Down syndrome. METHODS: Pregnancy outcome
      information was available for 5885 Taiwanese women under 35 years of age who had
      second-trimester maternal serum screening for Down syndrome, using AFP and free
      beta-hCG, and delivered a chromosomally normal fetus. Those with AFP at least 2.0
      multiples of the median (MoM), free beta-hCG at least 2.5 MoM, or a false
      positive screen (risk ratio at least 1:270) were identified, and the risk for
      adverse perinatal outcome was assessed. RESULTS: A serum AFP level at least 2.0
      MoM (n = 176, 3.0%) was significantly associated with the occurrence of preterm
      delivery, low Apgar scores, small-for-gestational-age infants, low birth weight
      or very low birth weight, fetal death, premature rupture of membranes,
      oligohydramnios, and a higher incidence of perinatal mortality. A serum free beta
      hCG level at least 2.5 MoM (n = 416, 7.1%) was significantly associated with low
      birth weight, an abnormally adherent placenta, and the occurrence of meconium
      stained amniotic fluid. A higher incidence of fetal structural anomalies other
      than neural tube or abdominal wall defects, large-for-gestational-age infants,
      and postpartum hemorrhage was observed for a calculated risk of at least 1:270 (n
      = 311, 5.3%) independent of the other biochemical markers. CONCLUSION: Asian
      women with unexplained elevations of serum AFP or free beta-hCG, or a false
      positive screen for Down syndrome are at increased risk for various adverse
      perinatal outcomes. Careful fetal ultrasound examination and thoughtful strategy
      for perinatal management are warranted for these patients.

PMID- 9170470
TI  - Second-trimester ultrasound markers for detection of trisomy 21: which markers
      are best?
AB  - OBJECTIVE: To investigate which second-trimester ultrasound markers for
      aneuploidy are the most diagnostically efficient in detecting fetal trisomy 21.
      METHODS: All second-trimester genetic sonograms performed since November 1, 1992
      for women at increased risk for fetal trisomy 21 were analyzed retrospectively.
      Statistical analysis included descriptive statistics, the test of proportions,
      and univariate and multivariable logistic regression analysis using trisomy 21 as
      the dependent variable and ten aneuploidy ultrasound markers as independent
      variables. RESULTS: There were 581 normal fetuses, 23 with trisomy 21 and four
      with other chromosomal abnormalities. When one or more abnormal ultrasound
      markers were present, the sensitivity and false-positive rate for trisomy 21 were
      87% and 13.4%, respectively. After adjusting for confounders, multivariate
      logistic regression analysis showed the best combination of ultrasound markers
      for detecting trisomy 21 to be nuchal fold thickening (relative risk [RR] 85.5;
      95% confidence interval [CI] 20.4, 357.7), pyelectasis (RR 25.2; 95% CI 6.7,
      95.0), and short humerus (RR 20.4; 95% CI 4.5, 92.1). The model combining these
      three ultrasound markers yielded a sensitivity of 87% and a false-positive rate
      of 6.7%. CONCLUSION: By using only three ultrasound markers (combination of
      nuchal fold thickening, pyelectasis, and short humerus) the false-positive rate
      is decreased from 13.4% to 6.7% without any compromise in the sensitivity (87%).
      The clinical usefulness of evaluating the various second-trimester ultrasound
      markers needs to be evaluated in prospective studies.

PMID- 9170471
TI  - Prenatal ultrasonographic diagnosis of fetal heart echogenic foci: no correlation
      with Down syndrome.
AB  - OBJECTIVE: To determine whether karyotype is indicated when fetal heart echogenic
      foci are encountered on prenatal sonogram. METHODS: Pregnant women who presented
      at two large district hospitals in Israel that treat 7200 gravidas per year, and
      in whom fetal heart echogenic foci were diagnosed, were studied prospectively.
      Identified cases had detailed prenatal and postnatal echocardiographic
      examinations, and pregnancy outcome was assessed. RESULTS: During 18 months, 2214
      low-risk pregnant women were examined sonographically, and 163 (7.4%) cases of
      fetal heart echogenic foci were detected at the first transvaginal sonography at
      13-16 weeks' gestation. On a repeat scan at 20-22 weeks' gestation, 59.5% of the
      foci could not be identified, leaving only 66 (3%) cases for postnatal
      evaluation. Left ventricle-right ventricle ratio for location of the fetal heart
      echogenic foci was 3:1; 4.9% of all cases had bilateral findings. The karyotypes
      of 16 fetuses were normal and no additional abnormalities were found. The
      remaining 50 cases were normal in appearance at delivery without any features
      that suggested trisomy 21. A review of the English language literature revealed
      that six of 489 cases with fetal heart echogenic foci (1.2%) had trisomy 21.
      However, statistical analysis of a hypothetical sample that produced these six
      cases revealed that the calculated risk of trisomy 21 in a fetus with fetal heart
      echogenic foci is about 0.002%. CONCLUSION: Karyotyping is unwarranted in the mid
      trimester fetus with incidental findings of fetal heart echogenic foci.

PMID- 9170472
TI  - Transvaginal sonographic imaging of early second-trimester fetal anatomy assisted
      by uterine fundal pressure.
AB  - OBJECTIVE: To assess the advantage of applying uterine fundal pressure to assist
      transvaginal sonographic imaging of early second-trimester fetal anatomy.
      METHODS: One hundred consecutive patients with singleton fetuses underwent
      routine transvaginal sonographic assessment of fetal anatomy between 13 and 17
      weeks' gestation. If the entire fetal anatomy including cardiac outflow tracts
      was not depicted, uterine fundal pressure was applied with the operator's
      nonscanning hand in a bimanual fashion, to facilitate transvaginal imaging.
      Transabdominal sonography was performed when visualization of the entire fetal
      anatomy was not obtainable with transvaginal or uterine fundal pressure-assisted
      transvaginal sonography. Observed fetal structures with and without fundal
      pressure were compared. Factors assessed that may have modified the value of
      fundal pressure included patient weight, gestational age, fetal presentation,
      previous abdominal surgery, and the presence of uterine fibroids. Statistical
      analysis included McNemar test, chi 2, Fisher exact test, and t test, with P <
      .05 considered significant. RESULTS: Visualization of lower limbs, head
      (including intracranial structures), upper limbs, kidneys, spine, gender, feet,
      hands (digits), face, four-chamber view, and cardiac outflow tracts was
      significantly enhanced by uterine fundal pressure-assisted versus nonassisted
      transvaginal sonography. Uterine fundal pressure improved transvaginal
      sonographic imaging in 91% of subjects, and in 51% of all subjects, a complete
      examination was thus obtained. In 20% of all subjects, transabdominal sonography
      was required to complete the examination. Complete fetal anatomic scanning was
      unobtainable despite uterine fundal pressure supplemented by transabdominal
      sonography in 29% of cases. Completion of the transvaginal sonographic fetal
      anatomic survey with uterine fundal pressure was related to gestational age (P <
      .02) and maternal weight (P < .05) yet not related to fetal presentation (P =
      .13), previous abdominal surgery (P = .06), or uterine fibroids (P = .26).
      CONCLUSION: Uterine fundal pressure applied during early second-trimester
      transvaginal sonographic evaluation of fetal anatomy significantly improves
      visualization of fetal structures otherwise located beyond the effective range of
      the transvaginal transducer.

PMID- 9170473
TI  - Umbilical venous velocity pulsations are related to atrial contraction pressure
      waveforms in fetal lambs.
AB  - OBJECTIVE: To identify the source of umbilical venous velocity pulsations, times
      of transmission from the atrial contraction pressure waveform to velocity waves
      in the inferior vena cava, ductus venosus, intra-abdominal umbilical vein, and
      intra-amniotic umbilical vein were examined. METHODS: Five lamb fetuses at 125
      135 days' gestation were instrumented with solid state pressure transducers in
      the inferior vena cava, fluid-filled catheters in the inferior vena cava and
      descending aorta, and epicardial pacemakers. Three to 5 days postoperatively,
      inferior vena cava, ductus venosus, and umbilical vein velocities were examined
      with Doppler ultrasound. Normal saline was administered and umbilical vein
      velocity pulsations developed (180 +/- 60 mL). In three fetuses, premature atrial
      contractions were induced under baseline conditions and after umbilical vein
      velocity pulsations developed. RESULTS: Times of transmission from the atrial
      contraction pressure waveform until velocity decreases in the fetal venous system
      were significantly different in the inferior vena cava, ductus venosus, intra
      abdominal umbilical vein, and intra-amniotic umbilical vein (P < .001). Times
      increased with the distance from the atrium. Inferior vena cava pressure
      increased with fluid administration from 3.7 +/- 4.7 mmHg to 9.3 +/- 2.3 mmHg (P
      < .01). Time from increased pressure waveforms with induced premature atrial
      contractions to the nadir of subsequent umbilical vein velocity waves decreased
      from 0.123 +/- 0.047 seconds before saline administration to 0.072 +/- 0.039
      seconds after saline administration (P < .001). CONCLUSION: Transmission time of
      atrial pressure into the venous circulation increases with distance from the
      atrium and decreases with volume loading. Umbilical venous velocity pulsations
      derive from atrial pressure changes transmitted in a retrograde fashion.

PMID- 9170474
TI  - Changes in hemodynamics, ventricular remodeling, and ventricular contractility
      during normal pregnancy: a longitudinal study.
AB  - OBJECTIVE: To investigate the hemodynamic changes occurring in normal pregnancy
      and to see if these changes were associated with an increase in myocardial
      contractility. METHODS: In a longitudinal study, primigravidas were studied with
      echocardiography in early (15 +/- 1.8 weeks), mid (26 +/- 1.2 weeks), and late
      (36 +/- 1.0 weeks) gestation, as well as at 6 weeks postpartum. Cardiac
      dimensions were measured with two-dimensional and M-mode echocardiography and
      hemodynamic indices were calculated. All measurements were made with subjects in
      the left lateral decubitus position. Statistical analysis was performed with
      repeated measures analysis of variance. RESULTS: Seventy-six women with normal
      pregnancy outcomes completed all four studies. From the baseline study to late
      gestation, an increase in cardiac output of 27% (from [mean +/- standard error]
      4.2 +/- 0.1 to 5.8 +/- 0.2 L/min, P = .001), and a decrease in total peripheral
      resistance of 33% (from 1356 +/- 69 to 941 +/- 37 dynes/second cm-5, P = .001)
      occurred. Over this same time period, left ventricular function, while
      demonstrating a small and non-significant increase in velocity of circumferential
      fiber shortening (from 1.25 +/- 0.02 to 1.27 +/- 0.02 cm/second), revealed a 12%
      decrease in wall stress (from 36.3 +/- 1.0 to 31.9 +/- 1.0 g/cm2, P = .001) and a
      13% decrease in the load-independent wall stress to velocity of circumferential
      fiber shortening ratio (from 30.0 +/- 1.2 to 26.1 +/- 1.0, P = .01), implying
      enhanced intrinsic myocardial contractility. CONCLUSION: Normal pregnancy is
      characterized by enhanced myocardial performance.

PMID- 9170475
TI  - Maternal oxygen desaturation with intravenous magnesium therapy.
AB  - OBJECTIVE: To describe the occurrence, treatment, and outcome of maternal oxygen
      desaturation during magnesium sulfate therapy. METHODS: A post hoc analysis of a
      randomized double-blind trial, designed to determine if mothers at risk for
      premature delivery treated with phenobarbital and vitamin K had less frequent
      intracranial hemorrhage in their newborns, was done. A subset of these patients
      at imminent risk for delivery received both intravenous magnesium sulfate and
      intravenous study drug (phenobarbital or placebo) and was monitored with maternal
      oxygen saturation monitoring. RESULTS: One hundred one women (29%) in the trial
      had pulse oximetry; 47 were assigned to placebo and 54 to the treatment group.
      The placebo and treatment groups had the following similarities: mean lowest
      oxygen saturation by pulse oximeter (93.4% +/- 3.0 compared with 93.1% +/- 3.3).
      mean highest magnesium levels (6.3 mEq/L +/- 1.5 compared with 6.2 mEq/L +/-
      0.9), frequencies of desaturation events defined as oxygen saturation below 90%
      (11% compared with 11%), gestational age at delivery, birth weight, Apgar scores,
      and cord arterial pH. Using regression analysis, multiple gestation was the only
      one of 14 independent variables associated with low maternal oxygen saturation.
      Preeclampsia was not associated with a greater risk of desaturation. The
      statistical power of this study is limited by its small sample sizes. CONCLUSION:
      Maternal oxygen desaturation occurs commonly with intravenous magnesium therapy,
      does not occur more frequently with simultaneous administration of intravenous
      phenobarbital, and does not cause decompensation in maternal or fetal status.
      Multiple gestation may be associated with lower maternal oxygen saturation.

PMID- 9170476
TI  - Changes in total, CD4+, and CD8+ lymphocytes during pregnancy and 1 year
      postpartum in human immunodeficiency virus-infected women. The Women and Infants
      Transmission Study.
AB  - OBJECTIVE: To assess changes in lymphocyte subsets during pregnancy and 1 year
      postpartum in human immunodeficiency virus (HIV)-infected women. METHODS: Changes
      in CD4+ and CD8+ cell counts, CD4 and CD8 percent, CD4/CD8 ratio, and total
      lymphocyte count and percent were assessed in each of 226 HIV-infected women
      followed during pregnancy and 1 year postpartum, and for each of 100 nonpregnant
      HIV-infected woman during 1 year. Trends over time were compared between pregnant
      women with and without several covariates. Postpartum changes over a 1-year
      period were compared to a 1-year period in the nonpregnant cohort. RESULTS: There
      was a mean increase of 2.76 per week in the CD4+ cell count during pregnancy (P =
      .04). No other characteristics changed significantly during pregnancy. The mean
      CD4+ and CD8+ cell counts, the CD8 percent, and the total lymphocyte count and
      percent increased immediately postdelivery. During the first postpartum year,
      there were statistically significant declines in the absolute CD4+ and CD8+ cell
      counts, the relative CD4 and CD8 percentages, and the total lymphocyte count and
      percentage. The rate of change for CD4+ and CD8+ counts, but not for CD4 percent,
      was less during 1 year in the nonpregnant cohort than in the first postpartum
      year, and the CD8 percent increased in the nonpregnant women. A wide variability
      in trends of all measurements during pregnancy was seen. CONCLUSION: During
      pregnancy, CD4 and CD8 percentages remain stable. There are no clinically
      significant changes during pregnancy or postpartum in any lymphocyte parameter we
      assessed. Postpartum changes in lymphocytes and lymphocyte subsets most likely
      represent a return to baseline from the physiologic changes of pregnancy and the
      immediate postpartum period.

PMID- 9170477
TI  - Pregnancy loss and autoantibodies against phospholipid-binding proteins.
AB  - OBJECTIVE: To evaluate the relationship between antibodies against beta 2
      glycoprotein I or prothrombin and pregnancy losses in women with antiphospholipid
      antibodies. METHODS: Women with antiphospholipid antibodies, (lupus anticoagulant
      and/or anticardiolipin antibodies), with (n = 41) and without (n = 61) a history
      of pregnancy loss were evaluated. Thirty-one out of the forty-one patients with
      pregnancy loss had early miscarriages (at less than 13 weeks) and ten patients
      had late miscarriages. Immunoglobulin (Ig)-G and IgM anti-beta 2-glycoprotein I
      and anti-prothrombin antibodies were measured by an enzyme-linked immunosorbent
      assay method. RESULTS: A significant association between pregnancy loss and
      positive IgM anti-beta 2-glycoprotein I antibodies was found (odds ratio 2.6; 95%
      confidence interval 1.03, 6.6; P = .043). Women with late pregnancy loss had
      higher levels of both IgG and IgM anti-beta 2-glycoprotein I antibodies compared
      with controls (P < .05). There was a good correlation between anticardiolipin and
      anti-beta 2-glycoprotein I antibodies levels (IgG: r = 0.75; IgM: r = 0.73). In
      contrast, there was no correlation between the levels of anticardiolipin or anti
      beta2-glycoprotein I antibodies and the levels of anti-prothrombin antibodies.
      Furthermore, the presence of anti-prothrombin antibodies was not associated with
      a history of pregnancy loss. CONCLUSION: The result of our study shows that there
      is a relationship between the presence of IgM anti-beta 2-glycoprotein I and
      previous miscarriages in women with anti-phospholipid antibodies.

PMID- 9170478
TI  - Usefulness of a breakfast test in the management of women with gestational
      diabetes.
AB  - OBJECTIVE: To assess the usefulness of a breakfast test in determining which
      women with gestational diabetes do not need self-monitoring of blood glucose
      levels (home monitoring). METHODS: A 1-hour post-standardized breakfast blood
      glucose below 7.8 mmol/L (140 mg/dL) was measured in 227 women and at or above
      7.8 mmol/L in 115. Within each group, women were randomized to home monitoring
      with a meter or to clinic follow-up. Target glucose values were 5.3 mmol/L (95
      mg/dL) fasting, 5.6 mmol/L (101 mg/dL) before meals, and 7.8 mmol/L (140 mg/dL) 1
      hour postprandial. Up to these thresholds women on clinic follow-up were
      transferred to home monitoring. Insulin therapy was started on the same
      thresholds in women randomized or transferred to home monitoring. Large for
      gestational age (LGA) newborns represented the main outcome, with the transfer
      rate to home monitoring and need of insulin therapy the secondary ones. RESULTS:
      The LGA delivery rate was not significantly different in the two follow-up groups
      in women with a breakfast result below 7.8 mmol/L (9.8 versus 4.3%) but was
      higher in the clinic follow-up among women with a breakfast result at or above
      7.8 mmol/L (13.3% versus 30.9%; P < .05). Fewer women with a breakfast result
      below 7.8 mmol/L were transferred to home monitoring (2.6 versus 52.7%; P < .001)
      or started on insulin therapy (3.6 versus 25.2%; P < .001). The breakfast test
      cutoff of 7.8 mmol/L predicted insulin need with a sensitivity of 91.0% and a
      specificity of 72.0% CONCLUSION: A breakfast test is useful in identifying a low
      risk population in which clinic follow-up may be used safety.

PMID- 9170479
TI  - Does hormone replacement therapy inhibit coronary artery calcification?
AB  - OBJECTIVE: To determine the association between the use of hormone replacement
      therapy (HRT) and coronary calcium, in postmenopausal women who had no history of
      coronary artery disease by double helical computed tomography (CT). METHODS: We
      used CT to compare the prevalence and extent of coronary calcium in 41
      postmenopausal women who were on HRT from the first year of menopause and 37 age
      matched controls who had never used HRT. RESULTS: Both groups had a similar rate
      of smoking, hypertension, a positive family history, and hypercholesterolemia.
      Coronary calcification was observed in 28.2% of the 78 women studied. The
      prevalence of coronary calcium was significantly lower among HRT users: six of
      the 47 (14.6%), compared with 16 of the 37 nonusers (43.2%) (P < .01). The
      recorded risk factors had no effect on the prevalence of coronary calcium.
      Stepwise logistic regression analysis, including age, coronary risk factors, and
      HRT use as independent variables, yielded HRT as the only variable determining
      the presence of coronary calcium (odds ratio = 0.2; 95% confidence interval 0.06,
      0.63; P = .006). CONCLUSION: The lower incidence of coronary calcium in the HRT
      users suggests that HRT is associated with decreased prevalence of the coronary
      calcification.

PMID- 9170480
TI  - Immunomodulation in women with endometriosis receiving GnRH agonist.
AB  - OBJECTIVE: To assess the changes in the subpopulations of lymphocytes and in
      lymphocyte mitogenic activity in women with endometriosis receiving GnRH-agonist
      treatment. METHODS: Twenty-six women with advanced endometriosis from the
      National Cheng Kung University Medical College were studied. Each received a
      total of six doses of GnRH agonist at 4-week intervals. Immunologic responses at
      various times after receiving GnRH-agonist treatment, including numbers of
      peripheral blood lymphocytes subsets and the lymphocyte proliferative activity,
      were analyzed using a repeated measures analysis of variance. Twenty-six healthy
      women who visited our gynecologic clinics for routine Papanicolaou smear
      examination at the time of the recruitment were enrolled as controls. The
      responses for each patient receiving GnRH agonist were normalized with respect to
      those of her matched control at each of the time points. The differences between
      post- and pretreatment data were estimated using generalized estimating
      equations. RESULTS: There was no significant difference in the sizes of
      lymphocyte subsets between patients and controls before treatment. After GnRH
      agonist treatment, there was a trend in the rise of natural killer cell numbers
      early in the treatment period, with P values of .05 and .07 at 1-2 weeks and 2-3
      weeks, respectively. This rise in natural killer cell numbers was not significant
      until 3-4 weeks and the second month after the treatment. There were no
      significant changes in the CD4+ and CD8+ T-cell subsets and B cells, although a
      slight increase in total T cells (ie, CD3+ T) was observed 1-2 weeks after
      receiving GnRH agonist. The T-cell mitogenic activities at the end of 2 and 4
      months after GnRH-agonist treatment were 1.5 and 1.8 times, respectively, of
      those before treatment. CONCLUSION: The increase in natural killer cell numbers
      and the upregulation of T-lymphocyte mitogenic activity, which might be caused by
      a direct effect of GnRH agonist or a consequence resulting from the depression of
      estradiol by GnRH agonist, may have implications in the clinical treatment of
      endometriosis.

PMID- 9170481
TI  - Contraceptive use among adolescent mothers at 6 months postpartum.
AB  - OBJECTIVE: To assess patterns and predictors of reliable and unreliable
      contraceptive use among adolescent mothers in the first 6 months following
      delivery. METHODS: We surveyed 462 women, 18 years of age or younger, at delivery
      and again at 6 months postpartum. Contraceptive behaviors were evaluated among
      the 359 adolescents who stated they were sexually active and not trying to
      conceive. RESULTS: Method discontinuation and switching were common during the 6
      month interval. Only 100 of 189 adolescents (53%) initially prescribed oral
      contraceptives were still using this method 6 months after delivery; ten of these
      100 stated that they had missed at least three pills in the last cycle. Twelve
      (10%) of the 115 adolescents who initiated depot-medroxyprogesterone acetate
      failed to obtain a second injection within 4 months of the initial injection or
      use an alternative method. In contrast nine of the ten women who received
      levonorgestrel implants were still using this method 6 months after delivery.
      Overall, 76% of the sample reported using reliable contraception at last
      intercourse. Multivariate analyses identified seven factors as predictive of
      reliable contraceptive use: school enrollment, not having failed a grade in
      school, adequate support, belief that pregnancy is likely without birth control,
      attendance at postpartum visit, prior abortion, and the adolescent's desire to
      wait at least 2 years before having another child. CONCLUSION: Interventions
      designed to reduce rapid repeat pregnancy during the adolescent years should
      address emotional, financial, and educational, as well as contraceptive, needs.

PMID- 9170482
TI  - Little knowledge and limited practice: emergency contraceptive pills, the public,
      and the obstetrician-gynecologist.
AB  - OBJECTIVE: To assess Americans' knowledge and attitudes about emergency
      contraceptive pills and the knowledge, attitudes, and practices of obstetrician
      gynecologists with respect to emergency contraceptive pills. METHODS: A random
      sample of a national cross-section of 2002 Americans, age 18 and older, including
      1000 women and 1002 men, was surveyed by telephone between October 12 and
      November 13, 1994. A nationally representative sample of 307 obstetrician
      gynecologists, whose names were drawn from the American Medical Association
      Physicians' Masterfile, was surveyed by telephone between February 1 and March
      21, 1995. Both Surveys addressed knowledge and attitudes about unplanned
      pregnancy and contraception options, including emergency contraception. Despite
      response rates of 50 and 77%, respectively, both unweighted samples closely
      mirror the populations from which they were drawn. RESULTS: Americans are not
      well informed about emergency contraceptive pills. Only 36% of respondents
      indicated that they knew "anything could be done" within a few days after
      unprotected sex to prevent pregnancy. Fifty-five percent said they had "heard of"
      emergency contraceptive pills, and only 1% had ever used them. Ninety-nine
      percent of obstetrician-gynecologists reported being "familiar" with emergency
      contraceptive pills. Twenty-two percent were "somewhat familiar." Among those who
      said they were "very familiar" with the method (77%), the majority considered
      emergency contraceptive pills to be "very safe" (88%) and "very effective" (85%).
      Overall, 70% of obstetrician-gynecologists surveyed said they had prescribed
      emergency contraceptive pills within the last year, but on an infrequent basis;
      77% of those who prescribed emergency contraceptive pills did so five or fewer
      times. CONCLUSION: Public knowledge about the availability and use of emergency
      contraceptive pills is limited, as is the practice of prescribing the pills among
      obstetrician-gynecologists. Because patients rely on health care providers for
      information on birth control, health care providers can improve knowledge about
      the availability of emergency contraceptive pills among their patients.

PMID- 9170483
TI  - Hormone replacement therapy as a risk factor for epithelial ovarian cancer:
      results of a case-control study.
AB  - OBJECTIVE: To evaluate the role of hormone replacement therapy (HRT) as a risk
      factor for the development of epithelial ovarian cancer. METHODS: A case-control
      study was performed that used 491 patients with epithelial ovarian cancer
      frequency matched for age at diagnosis (+/-5 years) with a control population of
      741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio
      (OR) for the development of epithelial ovarian cancer was estimated using
      logistic regression analysis with adjustment for age at diagnosis, parity, oral
      contraceptive use, smoking history, family history of epithelial ovarian cancer,
      age at menarche, menopausal status, income, and education. RESULTS: One hundred
      of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741
      patients (21.6%) in the control population had ever used HRT (OR 0.85; 95%
      confidence interval [CI] 0.62, 1.2). A significant association between HRT and
      specific histologic subtypes of epithelial ovarian cancer was not demonstrable
      for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), Clear cell carcinoma (OR
      1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A
      significant association between duration of use of HRT and the risk of developing
      epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI
      0.5, 1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95%
      CI 0.3, 1.4). CONCLUSION: A significant association between the use of HRT and
      the risk of developing epithelial ovarian cancer, even with prolonged exposure,
      is not demonstrable.

PMID- 9170484
TI  - Squamous cell carcinoma arising from mature cystic teratoma of the ovary: a
      clinicopathologic analysis.
AB  - OBJECTIVE: There have been few studies concerning the clinical pathology of
      squamous cell carcinoma arising from ovarian mature cystic teratoma. Thus, the
      objective of this study is to determine clinicopathologic factors affecting
      survival in this rare tumor. METHODS: From September 1979 to June 1996, 37
      patients with squamous cell carcinoma arising from ovarian mature cystic teratoma
      were treated by the Tokai Ovarian Tumor Study Group. A retrospective
      clinicopathologic and survival analysis of these patients was performed. The mode
      of infiltration was classified into expansive, moderately diffused, and diffused
      patterns. RESULTS: Although the 5-year survival rate was 94.7% and 80.0% for
      stage I and II patients, respectively, 12 of 13 patients with stage III died
      within 20 months (P = .0001). A significant difference was also observed between
      the survival of the groups with and without residual tumor at surgery (P =
      .0001). Pathologic features, grade, mode of infiltration, and vascular
      involvement were significant factors by univariate analysis. Multivariate
      analysis showed significant differences in survival related to grade (P = .0154)
      and mode of infiltration (P = .0053). The preoperative squamous cell carcinoma
      antigen level was significantly higher in the patients with squamous cell
      carcinoma arising from mature cystic teratoma than in patients with mature cystic
      teratoma (P < .0001). CONCLUSION: This study suggests that pathologic factors,
      grade, and mode of infiltration can provide valuable information for predicting
      the survival of patients with squamous cell carcinoma arising from mature cystic
      teratoma. In addition, squamous cell carcinoma antigen may be a useful marker to
      detect this disease preoperatively.

PMID- 9170485
TI  - Effect of a transportation incentive on compliance with the first prenatal
      appointment: a randomized trial.
AB  - OBJECTIVE: To evaluate the effectiveness of incentives for improving compliance
      with the first prenatal appointment. METHODS: One hundred four low-income women,
      intending to enroll for prenatal care in a system of Northern California family
      planning clinics, were recruited for a randomized trial. Study subjects were
      assigned randomly to one of three groups, receiving a taxicab voucher or a baby
      blanket coupon or an appointment slip (controls). Intention-to-treat analysis was
      used to compare compliance with the first prenatal appointment between the three
      groups. RESULTS: Subjects receiving the taxi voucher had a compliance rate of 82%
      for the first prenatal appointment, 22% higher than mean appointment compliance
      in the other groups. The odds ratio for missing the first appointment was 0.32
      (95% confidence interval 0.12, 0.88) in the taxi voucher group. This was not
      affected by controlling for possible confounders. Despite better appointment
      compliance, only one of 34 taxi vouchers distributed was actually used.
      CONCLUSION: A taxi voucher incentive was effective in improving compliance with
      the first prenatal appointment, despite the fact that only one subject actually
      used the voucher.

PMID- 9170486
TI  - Third-generation oral contraceptives and thromboembolism risk.
AB  - Recently, observational studies have suggested an increased risk of nonfatal
      venous thromboembolic complications in women using oral contraceptives (OCs)
      containing the third-generation progestins, gestodene and desogestrel. Because of
      the observational, rather than randomized, nature of these trials, the clinical
      relevance of these findings is difficult to interpret. Each study included one or
      more potential sources of bias. In particular, cases came almost exclusively from
      hospitalized patients with nonfatal venous thromboembolism, which represents only
      a minority of patients diagnosed with this condition according to current
      clinical practice. In the absence of a sound biologic rationale to explain the
      increased risk with third-generation OCs, and considering the potential sources
      of bias within the current studies, an alternative view argues against causality.
      Oral contraceptives remain safe and effective. Clearly, additional research is
      needed to determine the relationship between thromboembolic disease and the use
      of third-generation OCs. In the interim, women should be informed thoroughly with
      objective data on all risks associated with the use of OCs.

PMID- 9170487
TI  - Statistics for the Residency Review Committee: a clear windows approach.
AB  - Because the reporting requirements imposed by the Residency Review Committee
      (RRC) for Obstetrics and Gynecology have become more extensive, we sought to
      develop a Microsoft Windows 3.1 (Microsoft Corp., Redmond, WA)-based computer
      program for maintaining an on-line record of resident surgical experience. Data
      input for our program occurs in two stages. All residents are responsible for
      maintaining separate obstetrics and gynecology-primary care statistical booklets.
      Each booklet consists of individual perforated data sheets. The front of the
      obstetrics data sheets is a replica of the bottom portion of RRC S Form
      Obstetrics. The reverse side is a replica of the top half of S Form Obstetrics,
      listing all "accountable" obstetric procedures, coded by level of operator
      responsibility. The front of the gynecology data sheet replicates the S Form
      Primary and Preventive Ambulatory Medicine. The reverse of this sheet is a
      replica of S Form Gynecology and lists all "accountable" gynecologic procedures,
      again coded by level of operator responsibility. Residents submit data sheets on
      a daily basis to the residency program coordinator, who then enters each patient
      encounter into a user-friendly data base program. Data entry screens are
      essentially identical to the individual encounter forms, and input requires fewer
      than 30 seconds per form. Once the individual patient's data is entered on the
      screen, the computer program automatically updates the resident's cumulative
      surgical experience and stratifies experience by year of training. At any time,
      program administrators have on-line access to a comprehensive record of an
      individual resident's or group of residents' clinical experience.

PMID- 9170488
TI  - Premature rupture of membranes at term: a meta-analysis of three management
      schemes.
AB  - OBJECTIVE: To compare rates of cesarean birth, endometritis, chorioamnionitis,
      and serious neonatal infections among pregnancies complicated by premature
      rupture of membranes (PROM) at term and managed by immediate oxytocin induction,
      by conservative management (or delayed oxytocin induction), or by vaginal (or
      endocervical) prostaglandin E2, gel, suppositories, or tablets. DATA SOURCES: The
      English-language literature in MLD, LINE and other databases was searched through
      April 1996 using the terms "fetal membranes," "premature rupture," and "term."
      METHODS OF STUDY SELECTION: We included randomized trials comparing two or more
      management schemes for PROM at term. TABULATION, INTEGRATION, AND RESULTS: Twenty
      three studies with a total of 7493 subjects met the inclusion criteria and were
      included for analysis. Data regarding chorioamnionitis, endometritis, neonatal
      infections, and cesarean delivery were extracted. Meta-analyses were performed
      for the three interventions for these outcomes of interest using the Der-Simonian
      and Laird and Mantel-Haenszel techniques to estimate the pooled odds ratios
      (ORs). No statistically significant differences in cesarean deliveries or
      neonatal infections were noted among management schemes. Vaginal prostaglandins
      resulted in more chorioamnionitis than immediate oxytocin (OR 1.55, 95%
      confidence interval [CI] 1.09, 2.21), but less chorioamnionitis than conservative
      management (OR 0.68, 95% CI 0.51, 0.91). Immediate oxytocin induction resulted in
      fewer cases of chorioamnionitis (OR 0.67, 95% CI 0.52, 0.85) and endometritis (OR
      0.71, 95% CI 0.51, 0.99) than conservative management, although these results
      achieved significance only with the Mantel-Haenszel technique. CONCLUSION:
      Conservative management may result in more maternal infections than immediate
      induction with oxytocin or prostaglandins.

PMID- 9170489
TI  - The effect of amnioinfusion on the duration of labor.
AB  - OBJECTIVE: To test the hypothesis that women receiving intrapartum amnioinfusion
      have more rapid labors than do controls. DATA SOURCES: Prospective clinical
      trials of amnioinfusion published in major American obstetric and gynecologic
      journals between 1985 and 1995, identified through a literature search using
      MEDLINE and manual index review, were examined. METHOD OF STUDY SELECTION: Eleven
      studies that presented data regarding the length of labor were identified. Each
      study was reviewed for the design, number of subjects enrolled, volume of
      amnioinfusate, birth weight, maternal parity, interval from amniorrhexis to
      delivery, and total length of labor. TABULATION, INTEGRATION AND RESULTS: Meta
      analysis revealed no differences between amnioinfusion groups and controls with
      regard to length of labor or the interval between membrane rupture and delivery.
      CONCLUSION: Amnioinfusion has no effect on the duration of labor.

PMID- 9170490
TI  - Tips of the slongue: the enduring legacy of W.A. Spooner.
AB  - Slips of the tongue are common and often amusing phonic errors. Although surely
      not the first speaker to make such transpositions, W.A. Spooner (1844-1930) was
      well known for them and was the source of the eponym, "Spoonerism." Several of
      his noted slips are presented along with a whimsical obstetric presentation.

PMID- 9170491
TI  - Storage of newborn stem cells for future use.

PMID- 9170492
TI  - Complications and recovery from laparoscopy-assisted vaginal hysterectomy
      compared with abdominal and vaginal hysterectomy.

PMID- 9170493
TI  - Serum ionized magnesium levels in normal and preeclamptic gestation.

PMID- 9170494
TI  - Five complete genomes of JC virus type 3 from Africans and African Americans.
AB  - The central demyelinating disease progressive multifocal leukoencephalopathy
      (PML) is caused by the human polyomavirus JC virus (JCV). JCV evolved as
      geographically based genotypes of which Type 3 is an African variant first
      characterized in HIV-1 positive patients from Tanzania. This study reports the
      complete sequence of five JCV Type 3 strains. The entire JCV genome was PCR
      amplified from urine specimens of three African and two African-American
      individuals. The African consensus sequence was compared to the Type 1 and Type 2
      prototype strains, JCV (Mad-1) and JCV(GS/B), respectively. Type 3 differed in
      2.2% of its coding region genome from JCV (Mad-1) and in 1.3% from JCV(GS/B).
      Within the coding region the sequence variation among the three types was higher
      in the capsid protein VP1 and in the regulatory protein large T antigen than in
      the agnoprotein or in VP2/3. Notable Type 3-specific changes were located at
      sites adjacent to the zinc finger motif and near the major donor and acceptor
      splice junctions of large T antigen. Four of the five urinary Type 3 strains had
      an unrearranged, archetypal regulatory region. African strain #309 showed a 10-bp
      deletion at a location similar to that previously described for #307 from
      Tanzania. The African-American Type 3 strain #312 was closely related to the
      African consensus sequence. The complete genome of a urinary JCV strain from
      another African-American male, previously reported as a possible Type 5, showed a
      sequence difference of only 0.52% from the Tanzanian consensus and has been
      reclassified as a subtype of Type 3.

PMID- 9170495
TI  - Phylogenetic analysis of rabbit haemorrhagic disease and European brown hare
      syndrome viruses by comparison of sequences from the capsid protein gene.
AB  - A 398 bp fragment of the capsid protein (VP60) gene of 39 clinical samples of
      rabbit haemorrhagic disease virus (RHDV) and 17 of European brown hare syndrome
      virus (EBHSV), collected between 1981 and 1995 from 17 countries, was amplified
      by PCR and directly sequenced. The alignment of the nucleotide sequences and the
      subsequently constructed phylogenetic tree clearly separated RHDV from EBHSV as
      phylogenetic entities. The nucleotide homology rates between the RHDV and EBHSV
      groups ranged between 52.6% and 60.0%. The homology rates within the groups were
      much higher, 89.4% to 100% for the RHDV samples, and 89.4% to 100% for the EBHSV
      specimens. No intermediate viruses were found. Despite the high homology, three
      main branches could be identified in the phylogenetic tree of the RHDV samples,
      corresponding to the epizootiological data, while the EBHSV dendrogram did not
      show such well defined branches. The present results support the classification
      of RHDV and EBHSV as two distinct members of the Caliciviridae family.
      Nevertheless, a comparison with previously determined sequences of other
      caliciviruses shows that RHDV and EBHSV are more closely related to each other
      than to any other calicivirus.

PMID- 9170496
TI  - Sequence comparison of the 3'-terminal parts of the RNA of four German isolates
      of sugarcane mosaic potyvirus (SCMV).
AB  - The 3'-termini of the genome of four German isolates of sugarcane mosaic
      potyvirus (SCMV) were cloned and sequenced. The sequence data covered the 3' non
      coding region (3'NCR), coat protein and part of the nuclear inclusion b (NIb)
      genes of the isolates. Comparisons of the sequences revealed that the
      investigated isolates are very closely related. An alignment of the predicted
      coat protein amino acid sequences of the German isolates with sequence data for
      other members of the SCMV subgroup, in particular the two SCMV strains, SCMV-SC
      and SCMV-MDB, showed a limited degree of homology indicating that the German
      isolates may represent a distinct virus. However, this is mainly due to the
      previously reported unexpected sequence diversity in the surface exposed N
      terminal region of coat protein of SCMV isolates. Comparisons of the amino acid
      sequences of the core region of the coat proteins and the nucleotide sequences of
      the 3' NCR clearly show that the German isolates are strains of SCMV.

PMID- 9170497
TI  - Infection with human cytomegalovirus (HCMV) stimulates monocyte production of
      complement factor 3.
AB  - Complement biosynthesis in monocytes is stimulated by different microorganisms
      including Gram negative bacteria and yeasts. We have tested the effect of human
      cytomegalovirus (HCMV) on complement factor 3 (C3) production by cultured human
      monocytes. The monocytes were challenged with either a crude or a purified HCMV
      preparation obtained from the supernatant of HCMV-infected fibroblasts. When the
      monocytes were infected with 2 pfu/cell of virus and cultured for 2 days, the
      increase in C3 production compared to control ranged from 3% to 162%, median 62%
      (p < 0.01). However, crude HCMV was even more potent in stimulating C3
      production, as the increase in C3 values ranged from 104% to 507%, median 247% (p
      = 0.001). This indicates the presence in the crude HCMV preparation of a
      substance which acts synergistically with HCMV on the C3 production. When
      monocytes were stimulated by lipopolysaccharide (LPS), a well known inducer of
      C3, infection with crude or purified HCMV did not further increase C3 production.
      Both HCMV and substances produced during the propagation of HCMV in fibroblasts
      are able to stimulate C3 production in monocytes. Complement production by
      inflammatory cells may be of importance in host resistance against viral
      infections.

PMID- 9170498
TI  - Molecular characterisation of the 3'-end of the astrovirus genome.
AB  - We have sequenced the 3'-end of the RNA genomes of 14 serotyped and 12 untyped
      isolates of human astrovirus. The sequences, which include all 8 serotypes, were
      used to predict secondary structures, postulate possible functional domains,
      reveal conserved regions suitable for nucleic acid amplification and perform
      phylogenetic analysis. The final nucleotides of the capsid protein precursor gene
      and the adjacent 3'-noncoding region were highly conserved and, except for 35
      nucleotides with homology to a sequence in the 3'-end of a coronavirus RNA
      genome, unique to astrovirus family. This confirms that the 3'-end is a suitable
      target for universal and specific detection of astrovirus RNA. For the deduced 72
      C-terminal amino acids of the capsid protein precursor, distances between the
      serotypes were found to vary from 0.1 substitution per site between serotypes 3
      and 7 to more than one substitution per site between serotype 4 and the other
      serotypes. Different isolates of the same serotype were closely related, which
      indicates that the presently used type-specific antibodies differentiate between
      phylogenetically distinct groups. RNA secondary structures with minimal free
      energy were predicted using computer programs. Comparative sequence analysis
      verified the significance of certain of the predicted structural elements.

PMID- 9170499
TI  - In vivo growth of Epstein-Barr virus transformed B cells with mutations in latent
      membrane protein 2 (LMP2).
AB  - Epstein-Barr virus (EBV) causes infectious mononucleosis in adolescents and is
      associated with malignant B lymphocyte proliferation in AIDS patients, patients
      undergoing immune suppression for organ transplantation, and SCID mice. In vitro,
      EBV transformed, latently infected lymphoblastoid B cell lines (LCLs) contain EBV
      episomes and express nine virus encoded proteins. Six are nuclear proteins
      (EBNAs) and three are the integral membrane proteins, LMP1, LMP2A, and LMP2B. To
      determine if LMP2 was essential for in vivo growth, SCID mice were injected with
      LCLs containing wild-type EBV (LMP2+) or with LCLs transformed with EBV
      containing mutations in either LMP2A or LMP2B (LMP2-). SCID mice injected with
      the LMP2+ or LMP2- LCLs were monitored for tumor development, length of time to
      tumor development, and phenotypic characterization of the resulting tumors. No
      difference was observed in any of the above parameters between LMP2+ and LMP2-
      LCLs demonstrating that LMP2 is not essential for the in vivo growth of EBV
      transformed B lymphocytes in SCID mice.

PMID- 9170500
TI  - Genetic and functional complementation of the HSV1 UL27 gene and gB glycoprotein
      by simian alpha-herpesvirus homologs.
AB  - Utilizing co-transfection of DNA from glycoprotein gB- strain of HSV1 and cloned
      fragments of several simian alpha-herpesviruses containing the UL26, UL27 (gB
      glycoprotein), and UL28 gene homologs, replication-competent recombinant viruses
      were produced. Genetic analysis of one HSV1/SA8 recombinant (HSV1/SgB)
      demonstrated the presence of SA8 DNA comprising the entire UL27 (gB) gene and
      parts of the UL28 and UL26 ORFs in an otherwise HSV1 genome. The recombinant was
      shown to express the SA8 gB and p40 proteins (UL27 & UL26.5 gene products,
      respectively); all other proteins were indistinguishable from those of HSV1. The
      recombinant behaved like SA8 in gB-specific virus neutralization and cell surface
      antibody binding assays, while plaque morphology and replication kinetics were
      very similar to HSV1. Despite its overwhelming HSV1 genetic constitution, the
      recombinant displayed a pathogenic phenotype in mice very different from the
      parental HSV1. While HSV1 produced corneal disease in ocularly infected mice and
      readily spread to the nervous system. HSV1/SgB was markedly impaired in both
      respects. These results demonstrate the functional equivalency of the
      cercopithecine monkey virus gB glycoproteins and genes (including transcriptional
      regulatory elements) in HSV1, the functional nature of HSV1/SA8 chimeric UL28 and
      UL26 genes/proteins, and that UL28, gB and/or p40 proteins may effect the
      pathogenicity of HSV1.

PMID- 9170501
TI  - Comparison of field and vaccine strains of Australian fowlpox viruses.
AB  - The mild fowlpox vaccine, FPV M, widely used in Australia is composed of two
      predominant genotypes based upon differences identifiable in restriction enzyme
      analyses of plaque purified derivatives of this vaccine. The differences, where
      identifiable, were in the end fragments of the genomes. Five field isolates of
      FPV from chickens in New South Wales showed restriction enzyme profiles closely
      related to the more virulent (standard) vaccine strain, FPV S. The FPV S strain
      differs from FPV M in both terminal genome fragments and in the presence of a
      PstI fragment of approximately 10kb (this fragment was also present in PstI
      digests of all of the field isolates). Plaque purified derivatives of FPV M
      showed similar lesion development upon inoculation into the wing web of chickens.
      The field isolates showed significantly higher virulence in day-old and three
      week-old chickens in comparison with FPV M. One field isolate was similar to the
      FPV S vaccine. Two isolates had slowly developing wing web lesions, caused
      significant secondary lesions in three-week-old chickens and generalised poxvirus
      infection when inoculated into day-old chickens. For two isolates, the primary
      wing web lesion took even longer to develop and resolve although these isolates
      did not cause generalised poxvirus infection. It was possible to identify four
      virulence/pathogenicity types amongst these vaccine and field isolates of FPV.
      These strains may allow the characterisation of FPV encoded virulence factors.
      The field strains with higher virulence may be suitable as parent strains for the
      construction of FPV recombinants with enhanced immune responses to co-expressed
      vaccine antigens when compared with current FPV M strain based recombinants.

PMID- 9170502
TI  - Evolutionary relationships in the ilarviruses: nucleotide sequence of prunus
      necrotic ringspot virus RNA 3.
AB  - The complete nucleotide sequence of an isolate of prunus necrotic ringspot virus
      (PNRSV) RNA 3 has been determined. Elucidation of the amino acid sequence of the
      proteins encoded by the two large open reading frames (ORFs) allowed us to carry
      out comparative and phylogenetic studies on the movement (MP) and coat (CP)
      proteins in the ilarvirus group. Amino acid sequence comparison of the MP
      revealed a highly conserved basic sequence motif with an amphipathic alpha
      helical structure preceding the conserved motif of the '30K superfamily' proposed
      by Mushegian and Koonin [26] for MP's. Within this '30K' motif a strictly
      conserved transmembrane domain is present in all ilarviruses sequenced so far. At
      the amino-terminal end, prune dwarf virus (PDV) has an extension not present in
      other ilarviruses but which is observed in all bromo- and cucumoviruses,
      suggesting a common ancestor or a recombinational event in the Bromoviridae
      family. Examination of the N-terminus of the CP's of all ilarviruses revealed a
      highly basic region, part of which resembles the Arg-rich motif that has been
      characterized in the RNA-binding protein family. This motif has also been found
      in the other members of the Bromoviridae family, suggesting its involvement in a
      structural function. Furthermore this region is required for infectivity in
      ilarviruses. The similarities found in this Arg-rich motif are discussed in terms
      of this process known as genome activation. Finally, phylogenetic analysis of
      both the MP and CP proteins revealed a higher relationship of A1MV to PNRSV,
      apple mosaic virus (ApMV) and PDV than any other member of the ilarvirus group.
      In that sense, A1MV should be considered as a true ilarvirus instead of forming a
      distinct group of viruses.

PMID- 9170503
TI  - Tobacco veinal necrosis determinants are unlikely to be located within the 5' and
      3' terminal sequences of the potato virus Y genome.
AB  - Three potato virus Y isolates, representatives of distinct PVY groups, identified
      in potato fields in northern Poland were submitted to biological and molecular
      analysis. Phenotypically, two isolates, PVYN-Ny and PVYN-Wi, belong to the
      necrotic strain and the third one (PVYO-LW) to the common strain. PVYN-Wi,
      however, did not react with monoclonal antibodies directed against the necrotic
      strain isolates which recognise PVYN-Ny. To characterise the isolates, coat
      protein genes were sequenced and compared with sequences from databases. The
      necrotic PVYN-Wi isolate showed 99% amino acid homology with the common one-PVYO
      LW and significantly differed from the second necrotic isolate (PVYN-Ny).
      Sequence based homology matrix and phylogenetic analysis lead to classification
      of PVYN-Ny into group I, encompassing solely necrotic strain isolates, whereas
      PVYN-Wi falls into a phenotypically heterogeneous group II. The sequence analysis
      allowed for identification of putative group I-specific epitopes. 3'NTR (non
      translated region) sequences were identical for PVYN-Wi and PVYO-LW. The 5'NTR,
      P1 gene, coat protein gene and 3'NTR sequences of the common (PVYO-LW) and the
      necrotic (PVYN-Wi) isolates are 99-100% homologous. This suggests that tobacco
      veinal necrosis determinants are located outside the 3' and 5' terminal sequences
      of the PVY genome.

PMID- 9170504
TI  - Serological comparison of tospoviruses with polyclonal antibodies produced
      against the main structural proteins of tomato spotted wilt virus.
AB  - A new purification procedure for the tospoviruses of serogroups II and III was
      developed. SDS-polyacrylamide gel electrophoresis of purified tomato spotted wilt
      virus (TSWV; serogroup I), groundnut ringspot virus (GRSV: serogroup II), tomato
      chlorotic spot virus (TCSV; serogroup II) and impatiens necrotic spot virus
      (INSV; serogroup III) showed that the glycoprotein G2 of serogroup II members
      differs significantly in size from that of the serogroup I virus. Western
      immunoblot analysis using polyclonal antisera produced against purified
      glycoproteins TSWV-G1 and G2 as well as peptides of hydrophilic sequences of TSWV
      G1 and G2 expressed in Escherichia coli demonstrated a higher homology amongst G1
      of different serogroups than for G2. These results are supported by comparing the
      glycoprotein gene sequences of different serogroups.

PMID- 9170505
TI  - Foot-and-mouth disease virus-infected but not vaccinated cattle develop
      antibodies against recombinant 3AB1 nonstructural protein.
AB  - Foot-and-mouth disease (FMD) vaccines induce antibodies against structural and
      some nonstructural proteins present in vaccine preparations. To differentiate
      between FMDV-infected and vaccinated animals, we developed immunochemical assays
      capable of detecting antibodies against a FMDV nonstructural protein. Recombinant
      nonstructural 3AB1 protein was expressed in E.coli and in insect cells and used
      to detect anti-3AB1 antibodies. ELISA and Western blot analysis showed that sera
      from cattle infected with FMDV reacted with recombinant 3AB1 protein whereas sera
      from cattle which had been vaccinated against FMDV, mock-infected, or infected
      with different bovine viruses did not recognize the 3AB1 protein. In contrast,
      anti-virus infection associated antigen (VIAA) antibodies were present in both
      FMDV-infected and vaccinated animals. Detection of anti-3AB1 antibodies in sera
      of experimentally infected cattle obtained between 7 and 560 days postinfection
      indicated that immunological tests based on the detection of recombinant 3AB1
      protein could be used for the diagnosis of FMDV infection.

PMID- 9170506
TI  - Identification of three distinct antigenic sites in parapoxviruses.
AB  - Monoclonal antibodies (Mabs) were generated in BALB/c mice immunized with
      gradient-purified particles, envelopes and cores of intracellular mature orf
      virus D-1701. Three distinct antigenic sites were identified in this virus
      strain. Their topographical relationships was determined by pairwise epitope
      specificity studies in competition ELISAs. One MAb (class IgM) neutralized virus
      infectivity. Four micrograms/ml purified IgM gave a 50% reduction of 100 PFU of
      orf virus D-1701. As shown by immunogold electron microscopy (ELMI), all MAbs
      reacted with epitopes localized on the virus surface. Western blotting analysis
      demonstrated that two proteins of a Mr of 39kDa and 22kDa were the main targets
      for the Mabs. Cross-reactivity studies of several parapoxviruses (PPV)
      differentiated stomatitis papulosa virus strains from orf virus and milker's node
      virus (MNV) by a missing antigenic site.

PMID- 9170507
TI  - Identification of ovine herpesvirus-2 infection in sheep.
AB  - A polymerase chain reaction test for the detection of ovine herpesvirus-2 (OHV-2)
      DNA was used to identify sites of OHV-2 infection in peri-natal lambs and in
      adult sheep. OHV-2 was detected in the nasal secretions from all lambs within a
      period of two months following birth. Subsequently, OHV-2 DNA was identified in a
      number of epithelial tissues including the cornea, turbinates and pharynx. In
      addition, OHV-2 DNA was detected exclusively in B-lymphocytes from six of ten
      adult sheep tested. An infection cycle for OHV-2 in sheep is proposed which bears
      similarities with the gammaherpesviruses Epstein-Barr virus and mouse herpesvirus
      68.

PMID- 9170508
TI  - Complete nucleotide sequence of the genome of a severe cherry isolate of apple
      chlorotic leaf spot trichovirus (ACLSV).
AB  - The genome of the Balaton 1 severe cherry isolate of apple chlorotic leaf spot
      trichovirus (ACLSV-Bal1) has been cloned and sequenced. The genomic RNA is 7549
      nucleotide long, excluding the poly A tail. The genomic organization, with three
      overlapping open reading frames (ORF), is similar to that of the other sequenced
      ACLSV isolates. Sequence comparisons indicate a high variability between ACLSV
      isolates, with overall nucleotide sequence homology levels between 76 and 82%.
      The coat protein, encoded internally inside a larger ORF, is the most conserved
      protein (identity levels between 87 and 93%) while the central ORF, encoding the
      putative movement protein, is the most divergent (77 to 85% identity).

PMID- 9170509
TI  - Field evaluation of chicken egg yolk immunoglobulins specific for bovine
      rotavirus in neonatal calves.
AB  - The oral efficacy of chicken egg yolk immunoglobulins (yIg) specific for bovine
      rotavirus (BRV) serotypes G6 and G10 in protecting neonatal calves was examined
      in a herd of cattle under field conditions. In one of the three trials, yIg
      treated calves tested under high relative humidity (RH) showed a significantly
      increased mean body weight (P < 0.05) and a decrease in number of calves shedding
      high titer of BRV (G6) in stool compared to control calves (P < 0.01), suggesting
      that our yIg product was effective in a field condition with an epidemic outbreak
      of BRV diarrhea.

PMID- 9170510
TI  - Nucleotide sequencing of a part of the 5'-noncoding region of echovirus type 9
      and rapid virus detection during the acute phase of aseptic meningitis.
AB  - A part of the 5'-noncoding region of echovirus type 9 isolates was sequenced, and
      an attempt was made for rapid virus detection in clinical samples obtained from
      22 subjects hospitalized with aseptic meningitis. The sequence identity of 440-bp
      products amplified from the region by RT-PCR was 87.7% between the standard
      echovirus type 9(Hill strain) and the isolates. Specific IgM antibodies to Hill
      strain were positive in 45.5% by immunofluorescent antibody staining of virus
      infected cells. A high detection rate of PCR products was observed in
      cerebrospinal fluids (CSFs; 54.5%) at admission, and in peripheral mononuclear
      cells (PMCs; 72.7%) at the end of hospitalization. Viral genomes were detectable
      for 2 days in serum samples, and for 6 days in PMC samples after onset of
      disease. When specific IgM antibody titers were less than 1:40, the amplification
      rate of viral genome from serum samples was 50.0%. These results indicate that
      the combination of specific IgM determination and viral genome amplification from
      CSFs will be a rapid and reliable method for early diagnosis.

PMID- 9170511
TI  - Robert Doerr--prophet of the nature of viruses, founder of the "Archives of
      Virology".

PMID- 9170512
TI  - [Recent development of antitumor antimetabolites in Japan--cytosine arabinoside
      analogues].
AB  - Since there have been relatively high incidence of cancer of the digestive organs
      in Japan, many 5-fluorouracil analogues have been studied as the drugs to treat
      such cancers. Beside these fluoropyrimine compounds, cytosine arabinoside (ara-C)
      analogues have also been studied, and some of them have shown appreciable
      clinical activities against human malignancies. In this paper, as such analogues,
      experimental and clinical studies of gemcitabine (dFdC). DMDC and cytarabine
      ocfosfate were reviewed. Among these drugs, gemcitabine (Eli Lilly, Japan) showed
      more than 20% response rate against non-small cell lung cancer in the late phase
      II study in Japan. Unfortunately, clinical study of DMDC (Yoshitomi) is currently
      suspended because of the lack of the hint of clinical activity, but the author
      believes that this might show some clinical activities by changing the treatment
      regimens in the future. Cytarabine ocfosfate (Nippon Kayaku) has already put on
      market as the first drug to be active against ANLL and MDS by giving orally.

PMID- 9170513
TI  - [A Meaning for incurable patients to know the truth of their disease].
AB  - Actually most of unresectable solid cancers are incurable, except some pediatric
      cancers and germ cell tumors etc. For these patients, what doctors can provide is
      basically prolongation of life with acceptable quality. Without knowing the fact
      and possible advantage and disadvantage or side effect of any treatment, these
      patients cannot choose the treatment, either anti-cancer therapy or best
      supportive therapy. In such situation, prognosis is almost mandatory information.
      No body feels comfortable to hear severe facts of their diseases especially when
      they are hopeless. However, this information is essential to choose the treatment
      which has strong influence on their lives themselves. The 38 incurable patients
      and 33 with poor prognosis (cure rate will be less than 10%) treated by the
      author between 1993 and 1995 were analyzed to see the attitude of patients in
      such situation. After getting all information including effect and side effect of
      possible treatment, mean survival, and natural course of their disease, 24 out of
      70 selected supportive care. 11 of 70 requested consultation of a psychiatrist
      but all recovered soon with minimum treatment. In such critical or life
      threatening situation, decision is completely personal and cannot be done by
      their family. When doctors and patients can make a good relationship with
      confidence, patients can create their own style of remaining life and even death.

PMID- 9170514
TI  - [Cancer palliative medicine turning point in palliative oncology].
AB  - Hospice palliative care programs are rapidly growing in Japan. Although human
      science has attached importance comparing with natural science in this field, the
      latter approaches are recently developed to manage symptoms in terminal patients
      with advanced cancer. These scientific approaches include basic and clinical
      studies such as physiology, pharmacology, immunology, biochemistry, molecular
      biology, medical oncology, psycho-oncology and clinical ethics. These
      multidisciplinary approaches can clarify not only the mechanisms and relationship
      between cancer pain, cancer anorexia-cachexia syndrome and neuro-endocrine-immune
      systems with or without the abnormalities of body fluid, electrocyte balance,
      glucose-protein-lipid metabolisms but also clinical ethics and decision-making in
      terminal patients with advanced cancers. Based on these analyses, the strategies
      to modulate "homeostasis" for improving quality of life and even prolongation of
      life span could be developed in the near future. Our goal is to establish science
      based medical practice for management of symptoms and improving the quality of
      life through ethical and scientific clinical trials. Hospice-palliative care in
      cancer would be expected to confirm what the academic area has termed "cancer
      palliative medicine" or "palliative oncology".

PMID- 9170515
TI  - [Quality of life and chemotherapy in terminal stage of gastrointestinal cancers].
AB  - A patient in the terminal stage of gastrointestinal cancer is continuously
      worried by physical and psychological suffering, and asks for treatment to
      alleviate pain. We have conducted an assessment of the quality of life (QOL) in
      the terminal stage of cancer, and found a deterioration in active factor and
      total score of QOL 3 months before death. We have provided active chemotherapy in
      the terminal stage with the informed consent of the patient. The therapy has
      aimed at relieving suffering, prolonging survival and maintaining QOL.

PMID- 9170516
TI  - [Hospice program and palliative medicine].
AB  - Hospice and palliative care have important roles for cancer patients in an
      incurable state to alleviate their total pain and to achieve the best quality of
      life. Interdisciplinary team-doctors, nurses, therapists, social workers and so
      on provide effective support in order to fulfill the varying needs of patients
      and families. Pain relief as a palliative medicine is most urgently required by
      seventy percent of patients on admission to our Hospice at the Salvation Army
      Kiyose Hospital. A case is presented with some comments on pain management. Music
      therapy is also introduced. This is one of the complementary methods for
      consolation of the mind and body of patients. Some of them seem to find it
      beneficial.

PMID- 9170517
TI  - [Home terminal care for cancer patients].
AB  - Caring for terminal cancer patients at home is the ideal choice when the patient
      so desires and the relatives and the medical staff provide support. However there
      are numerous problems to overcome. Primarily the patient should understand the
      true nature of his or her disease, and the medical staff should be available for
      twenty-four-hour care, including telephone consultation, Doctors and nurses must
      have knowledge of palliative medicine as well as acquire communication skills.
      Crucial points in home care are the exchange of patient information with the
      hospital and the guarantee of hospitalization if necessary. It is desirable that
      home care doctors organize care teams which should be backed up by society and
      authority so as to be institutionally as well as financially feasible.

PMID- 9170518
TI  - [Clinical study of primary central nervous system lymphoma: the role of
      chemotherapy].
AB  - We conducted a retrospective study of 32 patients with histologically confirmed
      primary central nervous system lymphoma treated in our institute between 1971 and
      1995 with an emphasis on the role of chemotherapy. Thirty of the 32 patients
      underwent tumor resection, whereas 2 patients had biopsies only. Twenty-eight
      patients received adjuvant therapy, 9 of whom received radiation therapy alone, 2
      received chemotherapy alone, and 17 received both radiation therapy and
      chemotherapy. Chemotherapies performed were CHOP (cyclophosphamide, doxorubicin,
      vincristine, and prednisolone). VEMP or VENP (vincristine, cyclophosphamide,
      mercaptopurine [or Natulan], and prednisolone), intravenous ACNU (nimustine), and
      intravenous or intra-arterial MCNU (ranimustine) and CBDCA (carboplatin).
      Survival data were available for 30 of the 32 patients. The median survival time
      of this study was 12.5 months. Twenty-seven patients died from one month through
      79 months after the initiation of therapy, and 3 patients were alive for 13 to 69
      months. Two patients who received the combination of radiation therapy and
      chemotherapy survived longer than 5 years. Although radiation therapy and
      chemotherapy were individually both effective and prolonged the survival time,
      their combination was more effective. The median survival time was significantly
      shorter (7.0 vs 16.5 months, p < 0.05) for the patients who received radiation
      therapy alone than for the patients who received the combination of radiation
      therapy and chemotherapy. We conclude from our results and review of previous
      studies that it is important for the chemotherapy of primary central nervous
      system lymphoma 1) to apply a combination of a variety of effective drugs,
      similar to that for systemic malignant lymphoma, and 2) to make a sufficient
      amount of anti-cancer drugs penetrate the whole central nervous system, thereby
      satisfying the adequate dose intensity for each drug.

PMID- 9170519
TI  - [A comparative study between low-dose and high-dose medroxyprogesterone acetate
      (MPA) in the treatment of advanced and recurrent breast cancer--in relation to
      dose, serum concentration and response. Osaka Breast Cancer Research Group].
AB  - A prospective randomized study was carried out to evaluate the effectiveness of
      MPA in the treatment of breast cancer by comparing low dose (600 mg/day) with
      high dose (1,200 mg/day) of MPA. In 35 evaluable cases, the response rate to
      treatment was 40.0% (8/20) with low dose MPA and 26.7% (4/15) with high dose MPA.
      There was no significant difference between the two groups. The serum MPA
      concentration measured by high-performance liquid chromatography (HPLC) assay was
      23.2 +/- 17.6 ng/ml in the low-dose group and 89.5 +/- 56.7 ng/ml in the high
      dose group. Intrapatient variability in serum MPA concentration was relatively
      stable, but interpatient variability was large. No correlation was found between
      the response rate and serum MPA concentration. The above results indicate that a
      low dose of MPA (600 mg/day) is a useful treatment with high effectiveness and
      safety in advanced and recurrent breast cancer patients. Though no exact data on
      the optimal serum concentration could not be obtained, it was obvious that a
      successful response cannot be expected from a serum MPA concentration of less
      than 17 ng/ml, which was the average serum concentration in NC and PD patients of
      the low-dose group.

PMID- 9170520
TI  - [Glutathione levels in human colon cancer cell line M7609 following culture in a
      low sulfur amino acid medium and its sensitivity to various anticancer drugs].
AB  - Glutathione levels in human colon cancer cell line M7609 and its sensitivity to
      anticancer drugs were investigated in a complete medium RPMI-1640 (medium A) and
      an incomplete medium (medium B), which was prepared by removing glutathione and
      sulfur amino acids from medium A. Four different medium conditions were prepared
      by combining a medium A and a medium B; a medium of 100% medium A (Control), a
      50:50 mixture medium of medium A and medium B (Condition 2), a 20:80 mixture
      medium of medium A and medium B (Condition 3), and a 10:90 mixture medium of
      medium A and medium B (Condition 4). The cells were cultured in each medium for
      14 days, and intracellular levels of glutathione were determined to estimate the
      cell sensitivity to anticancer drugs. There were no significant differences in
      glutathione levels among the cancer agents in condition 2, as compared to those
      in the control. In condition 3, the reduced glutathione levels were decreased to
      23.1%, where CDDP, ADM, MMC and melphalane showed 2.5, 2.2, 1.8 and 1.5 times
      greater antitumor activity than in the control, respectively. In condition 4,
      cell proliferation was too low to collect adequate cells for glutathione
      determination. These results demonstrated that the decrease in cellular
      glutathione concentration with this method might enhance the cytotoxic effects of
      anticancer drugs.

PMID- 9170521
TI  - [Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker
      for urothelial cancer--NMP22 as a urinary marker for surveillance of bladder
      cancer. NMP22 Study Group].
AB  - This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear
      Matrix Protein 22) as a urinary marker for the surveillance of bladder cancer,
      especially in comparison with that of voided urine cytology. Urinary NMP22 values
      were determined for 144 patients with histologically diagnosed bladder cancer, 65
      patients with other urological cancers, and 171 healthy volunteers by use of a
      UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All
      bladder cancer patients were evaluated for urinary NMP22 values and voided urine
      cytology simultaneously from the same urine samples. Based on the data from the
      bladder cancer patients and the healthy volunteers, the cut-off value was set at
      12 U/ml. The median urinary NMP22 value for the bladder cancer patients was 17.8
      U/ml (95% CI: 13.1-29.0). The sensitivities of urinary NMP22 and voided urine
      cytology were 61.1% (88/144) and 33.8% (48/144), respectively, a significant
      difference (p < 0.00001). Multivariate analysis revealed that tumor size affected
      the urinary NMP22 values. The positive rate by tumor size was 42.3%, 59.1%, and
      85.0% for tumors of < 10 mm, 10-30 mm, and > 30 mm, respectively. Urinary NMP22
      values decreased postoperatively in 82.9% of the patients. The median NMP22
      values for prostate cancer and renal cancer were 4.4 U/ml (95% CI: 2.2-6.7) and
      6.2 U/ml (95% CI: 3.6-12.5). The positive rates were 24.2% and 31.3%,
      respectively, both of which were significantly lower than for bladder cancer. Our
      multicenter study indicates that urinary NMP22 test is more sensitive than voided
      urine cytology test for the surveillance of bladder cancer.

PMID- 9170523
TI  - [CPE chemotherapy for tongue carcinoma--clinical effects and side effects].
AB  - Recent advances in chemotherapy have markedly improved the treatment results for
      oral cancer. Among many chemotherapeutic regimens, the usefulness of multiple
      combination chemotherapy with cisplatin as the primary drug has been frequently
      reported. During the past 6-year period, we have performed combination
      chemotherapy with cisplatin as the primary drug, peplomycin, and etoposide (CPE
      chemotherapy) as one of the chemotherapeutic regimens for oral cancer. The
      subjects were 11 patients (7 males and 4 females) with tongue cancer treated by
      CPE chemotherapy as neoadjuvant chemotherapy at our department between March,
      1990 and April, 1995. RESULTS: PR in 8 (73%), and NC in 3 (27%). No patient
      showed CR and PD. The side effects observed were reversible findings such as
      transient myelosuppression, nausea-vomiting, and alopecia. No patient showed
      severe or persistent suppression of hematopoietic function.

PMID- 9170522
TI  - [Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker
      for urothelial cancer--screening for urothelial cancer in patients with
      microscopic hematuria. NMP Study Group].
AB  - This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear
      Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in
      patients with microscopic hematuria, especially in comparison with that of voided
      urine cytology. Urinary NMP22 values were determined for 183 patients with
      microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme
      linked immunosorbent assay. All patients were entered in this study before
      cystoscopy was performed, and were evaluated for NMP22 values and voided urine
      cytology simultaneously from the same urine samples. Of the 183 patients with
      microscopic hematuria, 14 cases of urothelial cancer were detected. For the other
      cases, 65 were of benign diseases and 104 were designated NED (No Evidence of
      Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED
      were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95%
      CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was
      significantly higher than for benign diseases and NED. When the cut-off value of
      urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial
      cancer was 85.7%, significantly higher than the 50% positive rate by voided urine
      cytology. This study indicates that urinary NMP22 is a useful tool for the
      screening of urothelial cancer in patients with microscopic hematuria.

PMID- 9170524
TI  - [A randomized comparative study of surgical adjuvant chemotherapy using 5
      fluorouracil and dl-leucovorin with CDDP 5-FU and dl-leucovorin for colorectal
      cancer].
AB  - A randomized comparative study of surgical adjuvant chemotherapy using dl
      leucovorin (dl-LV) and 5-fluorouracil (5-FU) (FL-therapy) with CDDP, 5-FU, and dl
      LV (PFL-therapy) was conducted. The following were the administration schedules:
      Arm A was 13 mg/m2 of CDDP, 300 mg/m2 of 5-FU, and 30 mg/body of dl-LV for 5
      consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5
      consecutive days. Both regimens were followed by biweekly administration of the
      same dose of dl-LV and 5-FU in outpatients. Arm A was started at the 26th
      postoperative day and arm B at the 21st day on average. Some 26 cases composed of
      11 cases of arm A and 15 cases of arm B completed the administration schedules.
      Only one case in arm A was complicated by local recurrence around 35 months after
      operation. Major toxicities were anorexia and neutropenia. Both toxicities were
      seen more in arm A than in arm B, showing complete recovery in all cases. These
      data suggest that PFL-therapy and FL-therapy seem to be possible and promising
      surgical adjuvant therapies for advanced colorectal carcinoma.

PMID- 9170525
TI  - [Clinical effect of two azasetron treatment methods against nausea and vomiting
      induced by anticancer drugs including CDDP].
AB  - Azasetron, a selective 5-HT3 receptor antagonist, has been previously shown to be
      highly effective in the prophylaxis of nausea and vomiting induced by anticancer
      drugs, and is widely used in the clinical setting in Japan. In order to improve
      the antiemetic effect of azasetron, we designed two treatment methods using this
      drug and compared the antiemetic effect of this method with that of standard
      bolus intravenous injection on nausea and vomiting associated with anticancer
      drug including 75 mg/m cisplatin (CDDP). The two-treatment group received an
      intravenous bolus injection of 5 mg azasetron before and 8 hours after the start
      of chemotherapy, and a standard group was given an intravenous bolus injection of
      10 mg azasetron only once a day. The inhibitory effect on vomiting in the two
      treatment group was significantly greater than those of the standard group on day
      1 and 2 (p = 0.0458, p = 0.0273), and the inhibitory effect on nausea of the two
      treatment group tended to be superior those of the bolus group on day 2 (p =
      0.0533). No adverse effects were observed in either group of this study. From
      these data, the two-treatment approach was considered to be highly effective in
      prophylaxis of nausea and vomiting induced by anticancer drug.

PMID- 9170526
TI  - [Induction chemotherapy based on histoculture drug response assay for a patient
      with advanced thymic cancer--a case report].
AB  - Histoculture drug response assay (HDRA) was applied to a biopsy specimen of
      advanced thymic cancer from a 68 years-old male patient. HDRA revealed that the
      tumor was not sensitive to CDDP but highly sensitive to 5-FU, ADM and MMC, which
      were administered as induction chemotherapy. The tumor regressed to 14% of the
      pretreatment size and was able to be completely resected with right and left
      brachiocephalic veins, superior vena cava, pericardium, right phrenic nerve and a
      part of right lung. Histologically, only a few small cancer nests remained in the
      fibrous tissue. The patient is alive and disease free 32 months after surgery.
      This result suggests that HDRA is useful to select anticancer agents which are
      sensitive to a rare kind of carcinoma such as thymic cancer.

PMID- 9170528
TI  - [Successful 5'-DFUR, CDDP and MMC combination therapy and 5'-DFUR and carboplatin
      combination therapy for a patient with inoperable advanced gastric cancer with
      peritonitis carcinomatosa].
AB  - A 71-year-old man with Borrmann type 3 gastric cancer and peritonitis
      carcinomatosa was treated with 5'-DFUR 600 mg/body p.o. daily, CDDP 50-80 mg/m2
      i.v. on day 1 and MMC 6 mg/m2 i.v. on day 2 after intraperitoneal injection of
      CDDP and OK-432. The cycle of CDDP and MMC was repeated every 4 or 5 weeks. After
      15 cycles of treatment, the primary gastric lesion disappeared and regional lymph
      node metastasis was reduced. Because of relapsing of the original lesion and
      concomitant renal dysfunction, a changed regimen of CDDP and Carboplatin was
      tried. Then the gastric lesion was reduced and lymph node metastasis disappeared.
      The patient has lived for about 3 years after diagnosis, but his gastric lesion
      is gradually worsening with duodenal invasion. This case indicates that these
      combination chemotherapies are quite promising as an effective treatment for
      advanced gastric cancer and good quality of patient's life.

PMID- 9170527
TI  - [Bone metastases responsive to pamidronate therapy in breast cancer].
AB  - A 66-year-old woman with locally advanced and metastatic breast carcinoma
      received combination chemotherapy, which comprised mitomycinC (total 84 mg) and
      anthracyclines (total : epirubicin 350 mg and pirarubicin 450 mg). She had been
      alive without tumor progression for more than one year thanks to these
      chemotherapies. Nevertheless, she thereafter complained of severe bone pain due
      to progression of bone disease. Since morphine administration could not give her
      sufficient pain relief, we tried to treat her bone pain with pamidronate in a
      dose of 30 mg weekly or biweekly. The pamidronate markedly relieved her bone pain
      and improved osteolytic bone lesions. In conclusion, pamidronate therapy can be a
      promising therapeutic modality for bone-derived pain in terminal patients.

PMID- 9170529
TI  - [A case of inoperable advanced gastric cancer remarkably responding to combined
      chemotherapy with UFT-E, MMC and PSK].
AB  - A 55-year-old male consulted a local doctor with the complaint of epigastralgia.
      Examination of the upper gastrointestinal tract revealed gastric cancer (Borrmann
      Type II) and he was referred to our hospital for operation. A few lymph nodes
      were palpable in the left supraclavicular fossa, and the biopsy of those lymph
      nodes revealed metastatic adenocarcinoma. The CT scan of the abdomen showed
      enlargement of paraaortic lymph nodes. Then, the patient was determined
      inoperable (T3, N4, H02 P01, M1 stage IVb). He was treated as an outpatient with
      UFT-E (300 mg/day, orally), Krestin (PSK 3.0 g/day, orally) and Mitomycin C (MMC
      6 or 8 mg once a week, intravenously repeated interval of 4 weeks). The total
      dose of UFT-E, PSK and MMC was 219 g, 1,095 g and 136 mg, respectively. One month
      later, lymph nodes in the supraclavicular fossa disappeared, and the lesion in
      the stomach completely responded. We have followed the patient for more than one
      year. He visits our the outpatient department and has kept working until now.

PMID- 9170530
TI  - [Two cases of advanced gastric cancer effectively treated with chemotherapy of 5
      fluorouracil, cisplatin and cytarabine].
AB  - We reported two cases of advanced gastric cancer effectively treated with
      chemotherapy of 5-fluorouracil (5-FU), cisplatin (CDDP) and cytarabine (Ara-C), 5
      FU (300-350 mg/body) was given by continuous intravenous infusion. Ara-C (20-40
      mg/body) by continuous infusion and CDDP (15-20 mg/body) were added intravenously
      for 3-6 days. For case 1, epirubicin (30 mg/body) was also given on the first day
      of each therapy course. Case 1 was a 62-year-old female who had gastric cancer
      with liver metastasis, ovarian metastasis and peritonitis carcinomatosa. After 3
      courses of the chemotherapy, reduction of ovarian metastasis greater than 75% was
      observed. The value of CA125 decreased from 6,800 U/ml to 527 U/ml and ascites
      disappeared. Case 2 was a 54-year-old male who had type 3 advanced gastric cancer
      with multiple liver metastases. He received 6 courses of the therapy. Both
      primary and metastatic tumors showed over 50% reduction in tumor size. These
      suggested that this combination therapy was effective for inoperable advanced
      gastric cancers.

PMID- 9170531
TI  - [Investigation of chemotherapy combined with peripheral blood stem cell
      transplantation (PBSCT) both in elderly and in recurred patients with small cell
      lung cancer].

PMID- 9170533
TI  - [TNM classification of carcinoma of the esophagus].
AB  - TNM classification of esophageal carcinoma was first described in the supplement
      to the first edition of the TNM classification in 1973. In the second edition,
      the classification was changed based on the data of 1,000 cases from the Task
      Force on Esophagus of American Joint Committee. In this edition, only the
      clinical classification was described, but the third edition included both
      clinical and post-surgical histopathological classification. But the criteria for
      T and pT classification differed. Before the fourth edition, specialists from
      Japan and the United States met in Hawaii in 1984. Data of the Japanese
      Nationwide Registration, including 7,742 patients from 1969 to 1978, were
      presented. After discussion based on these data, T was classified according to
      the depth of invasion, and perigastric lymph nodes were included in Regional
      Nodes in the fourth edition. Then, the TNM Research Committee of ISDE collected
      patient data of esophageal carcinoma from seven countries, and they were studied
      according to many factors. Based on these data, two proposals were made to the
      UICC TNM Committee. First, T1 should be divided into two categories: T1a, Tumor
      invasion of lamina propria; and T1b, Tumor invasion of submucosa. Second,
      metastases to distant lymph nodes should be grouped into the N classification
      instead of M classification. The first was accepted in the TNM Supplement of
      1993, and the second will be accepted in the Fifth Edition, which will appear in
      1997. It is important to accumulate data on many patients using the uniform
      registration form and to follow these patients very closely in the discussion of
      revisions to the TNM classification.

PMID- 9170534
TI  - 42nd Annual meeting of the Health Physics Society. San Antonio, Texas, 29 June-3
      July 1997. Abstracts.

PMID- 9170532
TI  - [Biweekly CHOP-E chemotherapy for aggressive non-Hodgkin's lymphoma].

PMID- 9170536
TI  - XXIV Annual meeting of the Arbeitsgemeinschaft Dermatologische Forschung.
      Leipzig, Germany, 24-26 January 1997. Abstracts.

PMID- 9170535
TI  - Society for Academic Emergency Medicine 1997 annual meeting. Washington D.C., May
      19-22, 1997. Abstracts.

PMID- 9170537
TI  - XIth World Congress of the International Society for Artificial Organs.
      Providence, Rhode Island, June 29-July 1, 1997. Abstracts.

PMID- 9170538
TI  - Extramural Grant Program 1996. Chicago, Illinois, June 4-5, 1996. Abstracts.

PMID- 9170540
TI  - 31st Annual scientific meeting of the European Society for Clinical
      Investigation. Kiel, Germany, 19-22 March 1997. Abstracts.

PMID- 9170539
TI  - 32nd Meeting of the Canadian Congress of Neurological Sciences. Saskatoon,
      Saskatchewan, June 24-28, 1997. Abstracts.

PMID- 9170541
TI  - [Material of the 2nd Congress of Pathophysiology of the Ukraine dedicated to the
      100th anniversary of the birthday of academician M.M. Sirotinin].

PMID- 9170542
TI  - 7th Annual meeting of the Society for Healthcare Epidemiology of America. St
      Louis, Missouri, April 27-29, 1997. Abstracts.

PMID- 9170544
TI  - American College of Sports Medicine 44th annual meeting. Denver, Colorado, May 28
      31, 1997. Abstracts.

PMID- 9170543
TI  - NOISE-CON 97. National Conference on Noise Control Engineering. State College,
      Pennsylvania, 15-17 June 1997. Abstracts.

PMID- 9170545
TI  - Europace '97. VIIIth Congress of the Working Groups on Cardiac Pacing and Cardiac
      Arrhythmias of the European Society of Cardiology. Athens, Greece, June 8-11,
      1997. Abstracts.

PMID- 9170546
TI  - 84th Annual meeting of the Swiss Society of Medical Radiology. Bale, 22-24 May
      1997. Abstracts.

PMID- 9170548
TI  - Undersea and Hyperbaric Medical Society annual scientific meeting. Cancun,
      Mexico, 19-21 June 1997. Abstracts.

PMID- 9170547
TI  - The Teratology Society 37th annual meeting. Palm Beach, Florida, June 21-26,
      1997. Abstracts.

PMID- 9170549
TI  - The physiological conundrum of hyperadrenergic orthostatic intolerance.
AB  - Orthostatic hypotension is a well-recognized medical problem in patients whose
      blood pressure falls dramatically with standing. Much less recognized is the
      syndrome of orthostatic intolerance. In patients with orthostatic intolerance,
      there are symptoms evoked by standing, but little actual fall in blood pressure.
      On the other hand, orthostatic intolerance patients frequently have a brisk
      tachycardia on standing. It has recently been recognized that many such
      individuals have a mild dysautonomia which may be brought on by conditions such
      as an antecedent viral illness, a rheumatologic disorder, or surgery/anesthesia.
      Recent studies of the hyperadrenergic (elevated plasma norepinephrine) subgroup
      of orthostatic intolerance is documenting a clinical spectrum including
      attenuated plasma renin activity and aldosterone, reduced supine blood volume
      coupled with dynamic orthostatic hypovolemia, elevated plasma norepinephrine and
      epinephrine, impaired clearance of norepinephrine from the circulation and
      evidence of partial dysautonomia. The emergence of partial dysautonomia as an
      important mechanism of orthostatic intolerance may lead to a substantial
      alteration in therapeutic approach.

PMID- 9170550
TI  - Responses of bat inferior collicular neurons to recorded echolocation pulse
      trains.
AB  - Under free field stimulation conditions, we studied the responses of inferior
      collicular neurons of the big brown bat, Eptesicus fuscus, to echolocation pulse
      trains which were recorded during the entire process of hunting. The entire
      series of recorded echolocation pulse trains was edited in different sequences
      according to echolocation pulses of different hunting phases. When stimulated
      with all edited sequences of echolocation pulse trains, the temporal
      characteristics and the relative position of the echolocation pulses of a
      specific hunting phase affect the number of impulses of each inferior collicular
      neuron studied. When stimulated with two different intensities, more than 59% of
      inferior collicular neurons studied discharged selectively to the echolocation
      pulses of a specific hunting phase such that the number of impulses discharged to
      the echolocation pulses of the most and least preferred hunting phases differed
      by at least 50%. Passible mechanisms for this selective response are discussed.

PMID- 9170551
TI  - Auditory P300, CT scans and cognitive state in Binswanger's disease.
AB  - The P300 component of evoked potential can reflect cognitive state in dementia
      patients. The purpose of this study was to investigate the value of P300 as an
      indicator of cognition in Binswanger's disease (BD) and to explore the possible
      causes of dementia in BD patients. P300 was measured at Cz site in 21 patients
      with BD and 21 controls matched with age, sex, handedness, and education. This
      measurement included P300 latency and amplitude. All patients were also given
      WAIS-RC test and scanned with computerized tomography (CT), and were treated with
      hyperbaric oxygenation (HBO). The relationships among P300, CT and WAIS-RC score
      were studied. BD patients had significantly prolonged P300 latency and a tendency
      of low amplitude P300, but the amplitude difference was not significant compared
      with controls. P300 latency was found to be negatively correlated with WARS-RC
      scale, and positively correlated with the change of white matter low attenuation
      (WMLA). WMLA was also correlated with WAIS-RC score. Treatment with HBO reduced
      P300 latency and had effect on the cognitive part of P300 but had no effect on CT
      changes. The significant association between neurophysiological and
      neuropsychological measurement suggests that P300 measurement reflects a
      disrupted aspect of cognitive function in BD patients, and it may be a useful
      means to assess the degree of subcortical cognitive deterioration and the effect
      of therapy. White matter lesion in BD is concerned to the occurrence of dementia
      by disturbing axonal conduction.

PMID- 9170552
TI  - Inhibition of corticosterone secretion by thyroxine in male rats.
AB  - The effects of thyroxine (T4) on the secretion of corticosterone both in vivo and
      in vitro in male rats were studied. Rats were thyroidectomized (Tx) or sham Tx.
      The Tx rats were subcutaneously with T4 (20 micrograms/kg) or saline once daily
      for two weeks. In an in vitro experiment, adrenal glands were incubated with
      ACTH, T4, or ACTH plus T4 in the presence or absence of 0.5 mM 3-isobutyl-1
      methylxanthine (IBMX) at 37 degrees C for 60 min. Medium and ether-extracted
      plasma samples were analyzed for corticosterone by radioimmunoassay (RIA). The
      accumulation of cyclic adenosine monophosphate (cAMP) in adrenal tissues after
      incubation with IBMX was measured by RIA. The levels of plasma corticosterone in
      Tx rats were significantly increased as compared with euthyroid rats. T4
      replacement in Tx rats restored plasma corticosterone to euthyroid level.
      Administration of T4 in vitro resulted in an inhibition of both basal and ACTH
      stimulated release of corticosterone. Both basal and ACTH-stimulated generations
      of cAMP in adrenal tissues were decreased by T4. These results suggest that T4
      inhibits the spontaneous and ACTH-stimulated secretion of corticosterone by
      acting directly at adrenal glands via a decrease in cAMP production.

PMID- 9170553
TI  - Altered intestinal transit is independent of gastroparesis in the early diabetic
      rats.
AB  - The object of this trial was to study whether deranged intestinal transit in
      diabetic rats should be responsible for their gastroparesis. Male Sprague-Dawley
      rats received i.v. injection of streptozotocin 5 days before the motility
      experiment. Diabetic induction led to a marked body weight loss. The rats were
      sacrificed 15 min after the feeding of radiochromium and charcoal contained test
      marker. Then the radioactivity represented gastric emptying and charcoal
      represented intestinal transit were counted. Diabetic induction delayed gastric
      emptying as compared with controls (mean +/- SE: 41.0 +/- 2.5% vs. 57.1 +/- 3.5%,
      p < 0.001) while the intestinal transit was also inhibited (34.2 +/- 1.4% vs.
      41.5 +/- 2.7%, p < 0.05). Diabetic gastric emptying values did not exhibit any
      correlation with intestinal transits but a correlation with plasma glucose levels
      was obtained (r = 0.522, p < 0.05). Gastric emptying values almost manifested a
      correlation with body weight ratios during the diabetic housing (r = 0.511, p =
      0.0515). We conclude that hyperglycemia is one of the mechanisms to delay liquid
      gastric emptying but the latter is not chiefly resulted from the deranged
      intestinal transit. Dysmotility is probable one of factors enabled to impair the
      body weight gain.

PMID- 9170554
TI  - Nucleus accumbens dopaminergic mediation of protection against gastric mucosal
      ulcerations by cold-restraint stress in the male hyperprolactinemic rats.
AB  - An investigation was undertaken to study the relationship between change in
      gastric lesion induced by cold-restraint stress and brain dopamine (DA) activity
      in male rat with chronic hyperprolactinemia. Male rats of Wistar strain were
      divided into two groups: one received extra two pieces of anterior pituitary (AP)
      from its littermates, the other grafted with several pieces of muscle served as
      control. Experiment I: From the 5th day to 40th day after transplantation, the
      levels of serum prolactin (PRL) in the AP-grafted group were higher than those of
      control (p < 0.05 or p < 0.01). Experiment II: On the 40th day after
      transplantation, AP-grafted and control rats were restrained and placed supine in
      a ventilated refrigerator with an ambient temperature of 5 degrees C for 3 hrs.
      Although gastric mucosal ulceration was observed in both groups, the ulcer index
      (including total number and length of gastric mucosal ulceration) was lower in AP
      grafted group than that in control group (p < 0.05 or p < 0.01). Experiment III:
      On the 40th day after transplantation, all rats were divided into AP-grafted and
      muscle-grafted rats. Subsequently, they were allowed to expose to cold-plus
      restraint stress and unstress (room temperature: 24 +/- 1 degrees C)
      respectively. After stress and unstress, all animals were immediately sacrificed
      by decapitation, the brains were dissected with Palkovits' micropunch technique.
      DA and its metabolites, DOPAC content in Nucleus accumbens (NAc) area of brain
      were assayed by HPLC with electrochemical detection. These results showed that
      concentrations of DA, DOPAC and their ratios (DOPAC/DA) in the NAc area of brain,
      were not statistically different under room temperature condition between muscle
      grafted and AP-grafted rats. The DOPAC/DA ratio in both groups showed significant
      increase in the brain's NAc area under cold-restraint stress condition as
      compared with unstress condition. But AP-grafted rats exhibited significantly
      higher DOPAC content in the brain's NAc area when compared with muscle-grafted
      rats under cold-restraint stress condition (171.7 +/- 22.1 versus 101.5 +/- 14.2
      ng/mg protein, p < 0.05). According to these findings, we suggest that reduced
      effect of chronic high serum PRL level from extra pituitary grafts on gastric
      mucosal ulceration produced by cold-restraint stress is probably mediated via
      Nucleus accumbens dopaminergic neuronal mechanism.

PMID- 9170555
TI  - Comparison of five measures derived from in vivo pulmonary vascular pressure-flow
      curves.
AB  - In order to facilitate evaluation of acute changes in lung vascular
      characteristics in vivo, pressure-flow (delta P-Q) curves of the pulmonary
      circulation were obtained by step-wise flow reduction. A balloon-tipped Swan-Ganz
      catheter was inserted via the jugular vein into the inferior vena cava of
      anesthetized, open chest, ventilated rabbits. Pulmonary arterial (Ppa) and left
      atrial (Pla) pressures were measured via catheters, and cardiac output Q by an
      electromagnetic flow probe on the aorta. Inflation of the balloon for 10 s
      reduced Q by 30-70%. delta P-Q curves were constructed by plotting a series of
      values of Q against corresponding delta P (= Ppa-Pla). To evaluate the
      feasibility and sensitivity of the method, these curves were compared under three
      conditions each paired with control (normoxia): hypoxia (8% O2), isoproterenol
      infusion, and serotonin infusion. Within our measured flow ranges, most delta P-Q
      plots were fairly linear, and extrapolated to a positive delta P intercept.
      Comparing slope, intercept, resistance, delta P at fixed Q, and Q at fixed delta
      P, we found that the latter two provided the more sensitive index to
      differentiate vasomotor changes. Since delta P-Q curves generally miss the
      origin, calculated pulmonary vascular resistance must depend on Q. Therefore,
      using the shifts in entire delta P-Q curves to select common range of Q and/or
      delta P is in general more quantitatively reliable for defining altered vascular
      characteristics.

PMID- 9170556
TI  - Phrenic nerve transfer in the repair of brachial plexus injuries: an animal
      model.
AB  - Ten young mongrel dogs underwent unilateral denervation of the brachial plexus.
      In six dogs, a 2-cm segment of phrenic nerve autograft was sutured to either the
      resected musculocutaneous nerve or the radial nerve. A hemoclip was applied to
      either musculocutaneous or radial nerve in the control groups. Five months
      postoperatively, the grafted musculocutaneous nerve demonstrated less fibrous
      tissue and less muscle atrophy of the biceps when compared to the control group
      with clipped nerve. In the group with the grafted radial nerve, the
      electromyographic findings of multiphasic action potential and muscle contraction
      from electric stimulation suggested reinnervation of the radial nerve. IN
      CONCLUSION: phrenic nerve transfer may be used to repair specific damages to
      nerve trunk with histological, electromyographic and clinical recovery.

PMID- 9170557
TI  - Spatial brain coherence during the establishment of a conscious event.

PMID- 9170558
TI  - Consciousness and cognition may be mediated by multiple independent coherent
      ensembles.
AB  - Short-term or working memory (WM) provides temporary storage of information in
      the brain after an experience and is associated with conscious awareness. Neurons
      sensitive to the multiple stimulus attributes comprising an experience are
      distributed within many brain regions. Such distributed cell assemblies,
      activated by an event, are the most plausible system to represent the WM of that
      event. Studies with a variety of imaging technologies have implicated widespread
      brain regions in the mediation of WM for different categories of information.
      Each kind of WM may thus be expected to involve many brain regions rather than a
      local, uniquely dedicated set of cells. Neurons in a distributed "cell assembly"
      may be self-selected by their temporally coherent activations. The process by
      which this fragmented representation of the recent past is reassembled to
      accomplish essentially automatic and reliable recognition of a recurrent event
      constitutes an important problem. One plausible mechanism to achieve the
      identification of past with previous events would require that the
      representational system mediating WM must coexist in spatial extent and somehow
      overlap in temporal activation with cell ensembles registering input from
      subsequent events. The detection of such a postulated mechanism required an
      experimental approach which would focus upon spatial patterns of coherent
      activation while information about different events was stored in WM and
      retrieved, rather than focusing upon the temporal sequences of activation in
      localized regions of interest. For this purpose, the familiar delayed matching
      from sample (DMS) task was modified. A series of information-free flashes, or
      "noncontingent probes," was presented before an initial series of visual
      information items, the Priming Sample, which were to be held in WM during a Delay
      Period. A second series of visual information items were then presented, the
      Matching Sample. The task required detection of any item in the second series
      which had been absent from the initial series. Thirty such trials with a
      particular category of visual information constituted a single task. Several DMS
      tasks with this standardized design, but with different categories of visual
      information, were presented within each test session. The information categories
      included letters of the alphabet, single digit numbers, or faces from a school
      yearbook. Event-related potentials (ERPs), were computed from 21 standardized
      electrode placements, separately for information-free probes and for information
      items in each interval of the trials within a task. Because each electrode is
      particularly sensitive to coherent activation of neurons in the immediately
      underlying brain regions, topographic maps were constructed and interpolated
      across the surface of the scalp. The momentary fluctuations of the resulting
      voltage "landscapes" throughout the task were then subjected to quantitative
      analysis. Distinctive landscapes sometimes persisted for prolonged periods,
      implying sustained engagement of very large populations of neurons. "Difference
      landscapes" were constructed by subtraction of topographic maps evoked by
      noncontingent probes during the Delay Period from maps of probe ERPs before the
      presentation of the initial information in the Priming Sample. Such probe
      difference landscapes displayed recurrent high similarity to momentary landscapes
      elicited during subsequent presentation of the information items in the Matching
      Sample. It seemed as if the distributed cell assembly continuously engaged by
      mediation of WM of the diverse attributes of the initial stimuli was being
      dynamically compared to the ensembles engaged by registration of the subsequent
      stimuli. Spatial Principal Component Analysis was applied to the sequences of
      momentary voltage landscapes observed throughout trials of each task. This method
      sought a small number of spatial patterns with which these large sets of
      inhomogeneous spatial distributions of voltage co

PMID- 9170559
TI  - Neural coherence and the content of consciousness.

PMID- 9170560
TI  - Consciousness and the organization of neural processes: commentary on John et al.

PMID- 9170561
TI  - Blindsight in hindsight.
AB  - Philosophers concerned with issues of mind have been turning to the
      neurosciences, especially neuropsychology, for empirical guidance. While I
      endorse this emphasis, I find that one important neuropsychological phenomenon,
      blindsight appears to have been misused by some prominent philosophers. In this
      paper, I examine this alleged misuse by spelling out the accounts of blindsight
      given by Daniel Dennett and Ned Block. I attempt to show that both Dennett and
      Block have ignored many complications surrounding blindsight including subjects'
      reports of visual sensations. This neglect has serious ramifications for their
      respective models of human consciousness which I also try to explicate. Further,
      by misrepresenting blindsight, these accounts serve to hamper scientific and
      philosophical understanding of the phenomenon and of consciousness. I conclude by
      sketching a model of blindsight that acknowledges these neglected details.

PMID- 9170562
TI  - A general model for the adaptive function of self-knowledge in animals and
      humans.
AB  - This article offers a general definition of self-knowledge that embraces all
      forms and levels of self-knowledge in animals and humans. It is hypothesized that
      various levels of self-knowledge constitute an ordinal scale such that each
      species in a lineage displays the forms of self-knowledge found in related
      species as well as new forms it and its sister species may have evolved.
      Likewise, it is hypothesized that these various forms of levels of self-knowledge
      develop in the sequence in which they evolved. Finally, a general hypothesis for
      the functional significance of self-knowledge is proposed along with
      subhypotheses regarding the adaptive significance of various levels of self
      knowledge in mammals including human and nonhuman primates. The general
      hypothesis is that self-knowledge serves as a standard for assessing the
      qualities of conspecifics compared to those of the self. Such assessment is
      crucial to deciding among alternative reproductive and subsistence strategies.
      The qualities that are assessed, which vary across taxa, range from the size and
      strength of the self to its mathematical or musical abilities. This so-called
      assessment model of self-knowledge is based on evolutionary biological models for
      social selection and the role of assessment in animal communication.

PMID- 9170563
TI  - Evaluative learning with "subliminally" presented stimuli.
AB  - Evaluative learning refers to the change in the affective evaluation of a
      previously neutral stimulus (NS) that occurs after the stimulus has been
      associated with a second, positive or negative, affective stimulus (AS). Four
      experiments are reported in which the AS was presented very briefly. Significant
      evaluative learning was observed in participants who did not notice the
      presentation of the affective stimuli (ASi) (Experiment 2) or could not
      discriminate between the briefly presented positive and negative ASi when asked
      to do so (Experiment 3). In two other experiments (Experiments 1 and 4), no
      significant learning effect was obtained. A meta-analysis performed on the
      present and previously reported results (De Houwer, Baeyens, & Eelen, 1994) gave
      evidence for a small, though statistically reliable evaluative learning effect
      when ASi are presented "subliminally." This finding supports the hypothesis that
      evaluative associations can be learned implicitly.

PMID- 9170564
TI  - Two forms of sequential implicit learning.
AB  - A serial reaction time (SRT) experiment tested the hypothesis that there are two
      independent forms of implicit learning: learning that is linked to making
      judgments about stimuli, and learning that is linked to motor processing.
      Participants performed 2, 6, or 12 blocks of single task SRT, dual task SRT, or
      observation with one of five sequence; each sequence had the same underlying
      structure. Participants then performed two implicit tests, SRT (a motor-linked
      test) and pattern judgment, as well as a generation test and an explicit
      knowledge test. There was a double dissociation of the effect of sequence surface
      structure on SRT and pattern judgment. SRT and pattern judgment competence
      developed independently of each other across length of acquisition task.
      Performance on both implicit tasks did not depend on explicit knowledge. These
      results indicate that the SRT and pattern judgment measures tap independent forms
      of implicit learning, which is consistent with the modular nature of memory and
      cognition.

PMID- 9170565
TI  - Similarities and differences between dreaming and waking cognition: an
      exploratory study.
AB  - Thirty-eight "practiced" dreamers (Study 1) and 50 "novice" dreamers (Study 2)
      completed questionnaires assessing the cognitive, metacognitive, and emotional
      qualities of recent waking and dreaming experiences. The present findings suggest
      that dreaming cognition is more similar to waking cognition than previously
      assumed and that the differences between dreaming and waking cognition are more
      quantitative than qualitative. Results from the two studies were generally
      consistent, indicating that high-order cognition during dreaming is not
      restricted to individuals practiced in dream recall or self-observation. None of
      the measured features was absent or infrequent in reports of either dreaming or
      waking experiences. Recollections of dreaming and waking experiences were similar
      for some cognitive features (e.g., attentional processes, internal commentary,
      and public self-consciousness) and different for other features (e.g., choice,
      event-related self-reflection, and affect).

PMID- 9170566
TI  - Interstitial cystitis.

PMID- 9170567
TI  - Ex vivo surgery for renal artery aneurysms.
AB  - BACKGROUND: Renal artery aneurysms (RAAs), once considered rare, are being
      recognized with increasing frequency. The treatment of aneurysms of the first
      ramification of the main renal artery is still controversial. METHODS: From
      November 1984 to May 1992, we treated 8 patients with RAA at the first
      ramification. All the patients were treated with an ex vivo technique and
      autotransplantation. RESULTS: The results, evaluated with intravenous pyelogram
      and arteriography were satisfactory. No operative deaths and no complications
      were noted. CONCLUSION: We concluded that surgery with an ex vivo technique and
      autotransplantation is an excellent method of treating this type of lesion.

PMID- 9170568
TI  - Effect of surgical stress on immune function in patients with urologic cancer.
AB  - BACKGROUND: To determine the immunosuppressive effect of surgery for urologic
      cancers, multiple variables of immune function were measured serially before and
      after operation in patients with urologic cancer. METHODS: Peripheral blood was
      obtained before operation and at postoperative day 7 and 14 from 20 patients with
      bladder cancer, renal pelvic, or ureteral cancer, or renal cell carcinoma.
      RESULTS: In patients with bladder cancer who were undergoing radical cystectomy
      with use of intestine for urinary diversion, the serum level of immunosuppressive
      acidic protein (IAP) increased, and serum levels of immunoglobulin (Ig)A, IgG,
      and IgM decreased after operation. In contrast, the number of CD25+ lymphocytes
      significantly increased. Transurethral resection of bladder cancer also resulted
      in an increase in serum IAP level, however, the number of CD4+ and human
      leukocyte-associated HLA-DR+ lymphocytes increased. In patients with renal pelvic
      or ureteral cancer undergoing nephroureterectomy with cuff, the level of serum
      IAP increased and serum IgG level decreased after operation. By contrast, the
      number of CD3+ lymphocytes increased. In patients with renal cell carcinoma,
      radical nephrectomy led to a significant increase in the number of CD8+
      lymphocytes. CONCLUSIONS: These findings suggest that surgical stress in patients
      with urologic cancer may result in both suppression and stimulation of host
      immunity.

PMID- 9170569
TI  - Phenotype frequency of human leukocyte antigens in Japanese patients with renal
      cell carcinoma who responded to interferon-alpha treatment.
AB  - BACKGROUND: Because of the high cost, low overall response rate (10% to 20%), and
      poor quality of life during interferon therapy for advanced renal cell carcinoma,
      it is important to distinguish patients likely to respond to treatment. The
      expression of human leukocyte antigens (HLA) may serve as a clinical marker for
      response to interferon treatment in patients with renal cell carcinoma. METHODS:
      We compared HLA phenotype frequency in 37 Japanese patients with advanced renal
      cell carcinoma who showed a favorable response to interferon-alpha, in 93 similar
      patients, before treatment, who did not receive interferon-alpha, and in 939
      healthy Japanese volunteers (historical control data). RESULTS: Six HLA antigens,
      B35, Bw48, Bw60, DRw6, DRw8, and DR9, were expressed at a significantly lower
      rate in the 93 pretreatment patients with renal cell carcinoma, compared with the
      control subjects. Three HLA antigens, excluding Bw60, DRw6, and DRw8, were
      expressed at a significantly higher rate in the patients who responded to
      interferon-alpha, compared with the pretreatment patients with renal cell
      carcinoma and control subjects. CONCLUSION: Three HLA antigens, B35, Bw48, and
      DR9, were expressed at a significantly higher rate in patients with renal cell
      carcinoma who showed a sensitivity to interferon-alpha, and could be important
      markers for clinical response to this antitumor therapy.

PMID- 9170570
TI  - Bladder dysfunction in patients with benign prostatic hyperplasia: relevance of
      cystometry as prognostic indicator of the outcome after prostatectomy.
AB  - BACKGROUND: We correlated cystometric findings to the clinical features of benign
      prostatic hyperplasia (BPH) and compared them in terms of outcome after
      prostatectomy. METHODS: Cystometric findings obtained from 78 patients who
      underwent prostatectomy were correlated with clinical features in BPH patients.
      In 41 consecutive patients of this group, prospective periodical cystometry was
      also performed. RESULTS: Low bladder compliance correlated significantly with an
      increase in age and prostate volume, detrusor instability and impaired
      contractility. Low compliance also correlated with irritative symptoms, decreased
      maximum flow rate, increased post-void residual urine and an increase in the
      American Urological Association symptom score. Postoperative persistent
      incontinence was associated with low bladder compliance and detrusor instability.
      In a prospective study, bladder dysfunction was not completely restored in 53% of
      patients examined at a mean interval of 7.7 months after prostatectomy.
      CONCLUSIONS: Among the cystometric parameters investigated, low compliance was
      the most relevant to the clinical features of BPH and had some predictive value
      for the outcome after prostatectomy. In about half of the BPH patients with
      bladder dysfunction preoperatively, this condition was irreversible for a
      significant period of time after prostatectomy, in spite of surgical relief of
      the infravesical obstruction.

PMID- 9170571
TI  - Transrectal ultrasonography to predict the clinical outcome of transurethral
      microwave thermotherapy in patients with benign prostatic hyperplasia.
AB  - BACKGROUND: This study evaluated the long-term efficacy of transurethral
      microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia
      (BPH), and determined whether the indices obtained with transrectal
      ultrasonography (TRUS) can predict the clinical response to TUMT. METHOD: Between
      November 1991 and June 1992, 43 patients with symptomatic BPH were treated with
      TUMT using the Prostcare device. The therapy consisted of a 1-hour treatment
      under topical anesthesia. The findings of uroflowmetry and AUA symptom score
      before treatment were compared with those obtained at each visit after the
      therapy. As the indices, the transition zone (TZ) volume, transition zone ratio
      (TZ ratio = TZ volume/total prostate volume), total prostate volume, and presumed
      circle area ratio (PCAR) were calculated. RESULTS: There was a significant
      correlation between pretreatment TZ ratio and residual urine volume (r = 0.472, P
      = 0.0022). The efficacy rates calculated by response criteria on the 3 point
      scale at 2 months, 12 months, and 30 months were 44.2%, 30.2%, and 25%,
      respectively. The significant prognostic factors that predicted the clinical
      effect 1 year after treatment were the TZ ratio and intraprostatic temperature.
      After controlling for the treatment temperature, the multivariate logistic
      regression model demonstrated that the TZ ratio was the significant predictor (P
      = 0.049) of 1 year efficacy of treatment. CONCLUSION: The present study showed
      that the efficacy rate of TUMT at 30 months was 25%, and that TRUS provides a
      simple parameter, the TZ ratio, which predicts the efficacy of TUMT.

PMID- 9170573
TI  - Correlation of transrectal ultrasonography and core biopsies with pathology
      results in radical prostatectomy specimens.
AB  - BACKGROUND: We compared preoperative tumor location, as identified by transrectal
      ultrasonography (TRUS), and TRUS-guided core biopsies with the final
      histopathological examination of radical prostatectomy specimens. METHODS: Thirty
      patients who had radical retropubic prostatectomy after evaluation with TRUS are
      included in the study. Diagnosis of prostate cancer was established with TRUS
      guided systematic (3 cores from base, mid and apex of the peripheral zone, and 1
      core from the transition zone of each side of the prostate) and lesion-directed
      core biopsies in all cases. Each prostate gland was halved for histopathological
      examination and results are reported in terms of "sides". RESULTS:
      Histopathological examination of the prostatectomy specimens revealed prostate
      cancer bilaterally in 29 glands (58 sides) and unilaterally in 1 gland.
      Preprostatectomy TRUS examinations missed cancer in 29 sides, and core biopsies
      were negative for cancer in 14 sides. CONCLUSION: This study revealed that 49% of
      prostate cancer lesions (n = 29 sides) were not recognized on TRUS and 52% of
      those (n = 15 sides) were diagnosed only by additional systematic biopsies.
      Furthermore, even with TRUS-guided systematic core biopsies, failure to detect
      the prostate cancer lesions may be as high as 24% (n = 14 sides).

PMID- 9170572
TI  - Pros-Eight transurethral radiofrequency thermotherapy for benign prostatic
      hyperplasia: preliminary clinical results.
AB  - BACKGROUND: We have developed a new transurethral thermotherapy device using 8MHz
      radiofrequency (RF) for the treatment of patients with symptomatic benign
      prostatic hyperplasia (BPH). We report the safety and effectiveness of the
      initial clinical experience with this device. METHODS: Sixty patients with
      symptomatic BPH were subjected to a single 1-hour treatment under local
      anesthesia. The treatment device uses extracorporeal RF capacitive heating in
      combination with radiative heating and conductive cooling of the urethra.
      RESULTS: In the 49 patients evaluable at 3 months, the mean International
      Prostate Symptom Score decreased from 17.8 to 13.1 (P < 0.0001) and the Quality
      of Life score decreased from 4.4 to 3.4 (P < 0.0005). Maximum flow rate increased
      from 8.1 to 9.7 mL/s (P < 0.05) at 3 months. Overall effectiveness by Homma's
      response criteria was as follows; excellent 4.1%, good 10.2%, fair 38.8% and poor
      46.9%. Side effects were minimal. Gross hematuria was seen in 3 patients and
      erosion of the external urethral meatus was seen in 2 patients, but none had
      urinary retention. CONCLUSIONS: In this initial clinical trial, transurethral RF
      thermotherapy was safe and resulted in modest symptomatic improvement. Further
      investigations for optimizing the treatment protocol seem warranted.

PMID- 9170574
TI  - Serum prostate-specific antigen values for the prediction of clinical stage and
      prognosis in patients with prostate cancer: an analysis of 749 cases.
AB  - BACKGROUND: The clinical significance of pretreatment serum prostate-specific
      antigen (PSA) values was studied to determine the ability to predict clinical
      stage and prognosis using a relatively large number of patients with prostate
      cancer. METHODS: Serum PSA values at diagnosis were analyzed from 749 patients
      with newly-diagnosed prostate cancer and registered in the Tokai Urological
      Cancer Registry. Correlations between the PSA value, the clinical stage and
      prognosis of the patients were evaluated. RESULTS: Serum PSA values at each stage
      of diagnosis showed positivity (> or = 3.6 ng/mL) in 23% (stage A1) to 91.2%
      (stage D2) of patients, and it was possible to obtain statistical differences
      between the stages, even between A1 and A2. Based on a cumulative study of PSA
      distribution, stages greater than A2 could be diagnosed using a cut-off of 7.2
      ng/mL, with a 99.2% positive predictive value (PPV), and a 16.2% negative
      predictive value (NPV). At a PSA level of 10.8 ng/mL, stages greater than B2
      could be predicted with a PPV of 95.3% but an NPV of 40.3%. Pretreatment PSA
      values were a significant prognostic indicator in stage D2 patients using 100 to
      150 ng/mL as the cut-off values. These differences were primarily found in the
      poorly differentiated group, which showed a statistical difference using cut-off
      PSA values from 75 to 150 ng/mL. CONCLUSIONS: Serum PSA levels from a large
      number of patients can be used to predict the stage and prognosis of prostate
      cancer patients.

PMID- 9170575
TI  - Recommended dose of flutamide with LH-RH agonist therapy in patients with
      advanced prostate cancer.
AB  - BACKGROUND: In a recent study by the Casodex Combination Study Group, USA,
      patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high
      treatment failure rate, mainly due to flutamide-induced diarrhea and
      hepatotoxicity. Our current study was conducted to determine the optimal dose of
      flutamide for use in this type of combination therapy. METHODS: In a randomized,
      multicenter study, 30 patients (hormone untreated; stage C or D) were divided
      into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg
      (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate
      (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin
      and leuprolide were administered to patients in a 1:1 ratio. Flutamide
      monotherapy at a daily dose of 375 mg was determined to be the optimal dose in
      Japan in our previous phase II study. The endpoints of this pilot study were the
      objective response and adverse events during the 12-week treatment. RESULTS: The
      objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the
      flutamide 175 mg group according to the Japanese response criteria for prostate
      cancer. Elevated PSA levels fell to within the normal range in 83.3% of the
      patients in the former group and in 93.3% of the patients in the latter group.
      One patient administered 250 mg of flutamide experienced diarrhea, while the
      serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide
      and 4 patients administered 375 mg of flutamide. CONCLUSIONS: Based on the
      findings of this pilot study of maximal androgen-depletion therapy for advanced
      prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH
      RH agonist. Assessment of the effects of our recommended regimen on longer term
      survival, quality of life and antiandrogen withdrawal syndrome of patients
      treated requires additional patients and time for follow-up.

PMID- 9170577
TI  - Effects of alterations in potassium and calcium concentrations on the pressure
      generated in rat whole bladder in vitro.
AB  - BACKGROUND: Various physiologic systems maintain the ionic equilibrium essential
      for normal neuron and smooth muscle function. These systems are impaired by
      nonphysiologic concentrations of extracellular cations. This study investigated
      the effects of altered extracellular concentrations of potassium and calcium on
      the in vitro pressure generation in the whole bladder of rats. METHODS: Pressure
      increases in response to field stimulation, as well as low and high doses of
      bethanechol, were determined in a Krebs solution containing a normal amount of
      potassium, and in excess of 10 mmol/L and 20 mmol/L of potassium. Each of these
      solutions had calcium concentrations, that were low (0.8 mmol/L), normal (2.5
      mmol/L), or high (7.5 mmol/L). RESULTS: The response to field stimulation was
      significantly decreased at the 20-mmol/L concentration of potassium in the
      presence of the different concentrations of calcium. The response to field
      stimulation increased as the extracellular concentration of calcium increased.
      The pressure increase caused by a low dose of bethanechol was significantly
      enhanced by elevations in the concentrations of both potassium and calcium. There
      was no difference in the response to a high dose of bethanechol in the presence
      of the various concentrations of potassium and calcium. CONCLUSION: These
      findings indicated that changes in the cationic equilibrium that result in
      blocking of the neuronal sodium channels, as well as increasing the level of
      intracellular bound calcium in smooth muscle, alter bladder function in vitro.

PMID- 9170576
TI  - Comparison of hormonal therapy and chemohormonal therapy in patients with newly
      diagnosed clinical stage D prostatic cancer.
AB  - BACKGROUND: In order to examine the usefulness of chemohormonal therapy, we
      conducted a multicentered randomized trial comparing hormonal therapy, using a
      luteinizing hormone-releasing hormone (LH-RH) agonist, with chemohormonal
      therapy, hormonal therapy plus cyclophosphamide (CPM), in patients with newly
      diagnosed clinical stage D prostatic cancer. METHODS: Between January 1991 and
      March 1995, 41 evaluable patients with stage D prostatic cancer were randomized
      into 2 groups: group A (hormonal therapy alone), goserelin acetate depot 3.6 mg
      subcutaneously every 4 weeks: group B (chemohormonal therapy), goserelin acetate
      depot 3.6 mg subcutaneously and CPM 1000 mg/m2 intravenously every 4 weeks. The
      responses to the therapies were evaluated based on the criteria of The Japanese
      Urological Association. RESULTS: There were no significant differences between
      the 2 groups with regard to objective and subjective response rates. No advantage
      in chemohormonal therapy was observed in the survival rate and progression-free
      survival rate. However, the survival rate and progression-free survival rate of
      responders were significantly higher than those of nonresponders in both groups.
      When the results were categorized by histologic grade patients with poorly
      differentiated adenocarcinoma had significantly higher response rates, survival
      rates, and disease-progression-free survival rates in Group B compared to similar
      patients in Group A. CONCLUSIONS: We conclude that chemohormonal therapy does not
      definitely improve the clinical response and prognosis of patients with stage D
      prostatic cancer; however, for patients with poorly-differentiated
      adenocarcinoma, chemohormonal therapy is a useful treatment.

PMID- 9170579
TI  - Adrenocortical adenoma producing 18-hydroxycorticosterone.
AB  - A 30-year-old man presented at our hospital with microscopic hematuria.
      Ultrasonography and computed tomography scanning revealed a right adrenal mass
      measuring 20 x 20 mm. The tumor was asymptomatic, but there was obvious
      accumulation on the right side when scintigraphy was performed with radioactive
      iodine (131I)-labeled adosterol. Endocrinology studies showed elevation of the
      plasma cortisol and renin concentrations, while the plasma aldosterone level was
      low. Right laparoscopic adrenalectomy was done on July 4, 1994. Histologic
      examination showed an adrenocortical adenoma. Serum levels of adrenocortical
      hormones were measured before and after surgery, and the tissue content for the
      same hormones was determined in the resected tumor. The hormonal studies showed
      that the tumor produced 18-hydroxycorticosterone.

PMID- 9170578
TI  - Effects of chronic renal failure on hypothalamo-pituitary-testicular axis
      function and fertility in rats.
AB  - BACKGROUND: We evaluated the effects of chronic renal failure on hypothalamo
      pituitary-testicular axis function in male Wistar rats. METHODS: Chronic renal
      failure was induced by five-sixths nephrectomy in male rats. Seven to 10 weeks
      after the surgery, serum area and creatinine concentrations and hematocrits were
      evaluated, and human chorionic gonadotropin (hCG) and gonadotropin-releasing
      hormone (GnRH) tests, and prolactin stimulating and suppression tests were
      performed. In addition, androgen-binding protein, epididymal sperm content,
      motility, and fertile potential were assessed. RESULTS: Basal serum testosterone
      concentrations and the response of testosterone to hCG were significantly lower
      in rats with chronic renal failure than in controls. Basal serum gonadotropin
      levels were elevated in rats with chronic renal failure, but the gonadotropin
      response to GnRH did not differ from that in controls. Serum prolactin levels
      responded appropriately to stimulation and suppression tests. Androgen-binding
      protein levels, epididymal sperm content, motility, and fertile potential were
      significantly lower in chronic rats. CONCLUSIONS: Chronic renal failure in rats
      interferes with endocrinologic mechanisms and testicular functions. Thus, uremic
      rats have a low fertile potential.

PMID- 9170580
TI  - Bilateral deoxycorticosterone-secreting adrenocortical adenoma.
AB  - A case of a 58-year-old man with bilateral deoxycorticosterone (DOC)-secreting
      adrenocortical adenoma is reported. Before surgery, plasma levels of DOC and
      corticosterone were markedly elevated, but both adrenal hormone levels normalized
      after the surgical removal of the bilateral adrenal tumors. The histologic
      examination revealed bilateral adrenocortical adenoma, but curiously, the tissue
      concentrations of DOC and corticosterone were elevated only in the right adrenal
      gland.

PMID- 9170581
TI  - Diagnosis and treatment of renal hydatid disease: presentation of four cases.
AB  - Hydatid disease of the urinary tract is uncommon, accounting for only 2% to 1% of
      all hydatid diseases. We report 4 patients with hydatid cystic disease of the
      kidney. Nephrectomy was performed on 1 patient because of the destruction of
      renal parenchyma by the hydatid cyst. The other 3 patients were treated by
      cystectomy to preserve the normal renal parenchyma. In these cases, Casoni's
      intradermal test and indirect hemagglutination (IHA) test were not found to be
      helpful in the diagnosis, and eosinophilia was not significant. Diagnostic
      features of hydatid cysts were mixed echogenicity on ultrasonography, and
      multivesicular cyst with mixed density on computerized tomography (CT). CT was
      the most useful and specific investigation. No complications were noted during
      the first 3 months of the follow-up. Despite its rarity, hydatid disease should
      be considered in the differential diagnosis of space-occupying lesions of the
      urinary tract. Parenchyma-sparing surgery (cystectomy, partial nephrectomy) or
      nephrectomy are the main treatment modalities.

PMID- 9170582
TI  - Solitary colonic metastasis of renal cell carcinoma seven years after
      nephrectomy: a case report.
AB  - An 83-year-old man, who had undergone right radical nephrectomy for renal cell
      carcinoma about 7 years previously, experienced melena and abdominal mass. Barium
      enema, colonoscopy, computed tomography, and arteriography showed a hypervascular
      mass on the transverse colon, and a partial transverse colectomy was performed.
      The postoperative histologic examination revealed that the tumor was a metastatic
      clear cell carcinoma.

PMID- 9170583
TI  - Inferior vena cava filter used for unresectable renal cell carcinoma with tumor
      thrombi.
AB  - A titanium Greenfield inferior vena cava filter was used for the treatment of 2
      patients with unresectable renal cell carcinomas with tumor thrombi to prevent a
      fatal pulmonary embolism induced by tumor clots released during systemic
      interferon therapy and embolization of the primary tumor. After treatment, the
      size of the renal cell carcinomas at the primary site and the tumor thrombi
      decreased by 50%. There were no fatal pulmonary embolisms or complications
      related to the filter during the observation period (24 and 25 months) after
      therapy. This method may be useful in the prevention of a fatal pulmonary
      embolism induced by embolization and systemic interferon therapy in these
      patients.

PMID- 9170584
TI  - Acute thrombosis in a contralateral kidney after radical nephrectomy: successful
      treatment by thrombolytic therapy using a tissue-type plasminogen activator.
AB  - A 67-year-old male became anuric immediately after a right radical nephrectomy
      for renal cell carcinoma. The patient was diagnosed with an acute arterial
      thrombosis of the remaining kidney within 4 hours after surgery by both CT scan
      and angiography. Thrombolytic therapy was started by a transcatheteral infusion
      of tissue-type plasminogen activator (TPA) resulting in a complete
      recanalization. Hydration and systemic administration of heparin followed, and
      renal function recovered within 3 weeks. This is the first report of acute
      thrombosis in a contralateral renal artery immediately after a radical
      nephrectomy which was successfully treated with TPA. It is probable that
      compression of the contralateral renal artery by the retractor for an extended
      period of time during surgery led to this unfavorable condition.

PMID- 9170585
TI  - Papillary cystadenocarcinoma of the prostate.
AB  - We report a papillary adenocarcinoma with cystic formation in the prostate of a
      64-year-old man, who presented with gross hematuria and pollakisuria.
      Immunohistochemically, the origin of this tumor was considered to be the prostate
      gland. Interestingly, this tumor grew into the muscle layer of the bladder with
      large glandular formation but no stromal changes.

PMID- 9170586
TI  - Tuberculoma arising in the inguinal portion of the spermatic cord: a case report.
AB  - A 50-year-old man was treated with excisional surgery for an asymptomatic
      inguinal spermatic cord mass. The lesion was proved to be tuberculous, and there
      was no apparent coexisting active disease elsewhere in the body. In addition to
      an intraoperative frozen-section examination, clinical findings of a strongly
      positive tuberculin skin test and normal erythrocyte sedimentation rate are
      considered to be helpful in establishing the diagnosis of a tuberculoma arising
      in either the scrotal or inguinal position.

PMID- 9170587
TI  - Fat is a health issue.

PMID- 9170588
TI  - Infant metabolic screening: a total quality management approach.
AB  - The principles of total quality management (TQM) were used to improve the infant
      metabolic screening program in a large urban hospital. Three quality indicators
      needed improvement; unsatisfactory specimen quality, delayed delivery to the
      state laboratory for testing, and specimen slips missing the date of collection.
      A multidisciplinary team identified the root causes of the poor quality and
      implemented remedies. Dramatic improvement in three infant screening indicators
      occurred within a 4-month period. Evaluation of the three indicators continued
      for the following 3-year period. Quality improvement programs that involve a
      multidisciplinary approach benefit the patient and staff and may reduce costs.

PMID- 9170589
TI  - Phenytoin as an alternative treatment for preeclampsia.
AB  - Magnesium sulfate is the preferred treatment for preeclampsia in the United
      States. Its use has been criticized because of the maternal, fetal, and neonatal
      side effects and its tocolytic action during labor. Phenytoin has been identified
      as an alternative for the treatment of preeclampsia and the prevention of
      eclampsia. The effects of magnesium sulfate with those of phenytoin on the
      mother, the fetus, and the neonate are compared. A nursing protocol summarizes
      nursing care for the obstetric patient receiving phenytoin. Phenytoin has certain
      demonstrable clinical advantages when used in the intrapartum period with
      patients with preeclampsia.

PMID- 9170590
TI  - Von Willebrand disease: a nursing perspective.
AB  - Von Willebrand disease, caused by a deficiency or abnormality of von Willebrand
      factor, is the most common hereditary bleeding disorder, occurring in
      approximately 1% of the population. This article is intended to raise the level
      of awareness in the health care community and define the nurse's role in
      recognizing the clinical presentation of this underdiagnosed bleeding disorder.

PMID- 9170591
TI  - The role of the clinical research coordinator in multicenter clinical trials.
AB  - The clinical research coordinator plays a crucial role in organizing a site's
      participation in the expanding arena of multicenter medical and pharmacologic
      clinical trials. This summary clarifies the role of the clinical research
      coordinator for inexperienced staff members assuming these responsibilities and
      outlines planning procedures leading to successful implementation. Emphasis is
      placed on establishing an interdependent relationship with the principal
      investigator, careful protocol assessment, team building, and staff feedback.
      Useful tools such as study manuals and physicians' study orders are described.

PMID- 9170592
TI  - Breastfeeding incidence after early discharge and factors influencing
      breastfeeding cessation.
AB  - OBJECTIVE: To determine if the incidence of breastfeeding at 6 to 8 weeks
      postpartum differs for a mother who had a (usual) 48-hour length of hospital stay
      versus a mother with a (shortened) 24-hour length of stay and what factors
      influenced the change from breastfeeding to bottle feeding. DESIGN: A descriptive
      two-group survey. PARTICIPANTS: A convenience sample of 101 primiparous
      breastfeeding women who had vaginal deliveries of healthy newborns and were
      between 6 and 8 weeks postpartum. OUTCOME MEASURE: The incidence of breast and
      bottle feeding at 6 to 8 weeks postpartum and what perceived factors influenced
      the decision to change to bottle feeding. CONCLUSIONS: No difference was found in
      the incidence of breastfeeding at 6 to 8 weeks postpartum for mothers who had a
      48-hour length of stay versus mothers who had a 24-hour length of stay with a
      home visit. Additional studies of the factors influencing change from breast to
      bottle feeding should be conducted.

PMID- 9170593
TI  - Metabolic bone disease in very-low-birth-weight infants: assessment, prevention,
      and treatment by neonatal nurse practitioners.
AB  - OBJECTIVE: To describe the current practice of neonatal nurse practitioners in
      assessing skeletal health and preventing and treating metabolic bone disease in
      very-low-birth-weight infants. DESIGN: Descriptive, retrospective survey.
      PARTICIPANTS: Neonatal nurse practitioners in the continental United States were
      systematically randomly selected. A 64% response rate was obtained (112). MAIN
      OUTCOME MEASURES: Responses to questions about assessing skeletal health and
      preventing and treating metabolic bone disease in very-low-birth-weight infants.
      RESULTS: Current practice of neonatal nurse practitioners includes assessing
      skeletal health of very-low-birth-weight infants on the 7th (47.3%) or 14th
      (19.6%) day of life, with subsequent assessments every 7 (63.3%) or 14 (18.8%)
      days. Neonatal nurse practitioners (85.1%) estimate the incidence of metabolic
      bone disease at less than 15%. Neonatal nurse practitioners initiate total
      parenteral nutrition (99%), provide parenteral calcium and phosphorous in ratios
      of 1.3-1.7:1 (9%), and add powdered fortifier (90.1%) and liquid fortifier
      (25.2%) to expressed breast milk. All respondents use formulas made for premature
      infants. Physical therapy is used by 46.8% of neonatal nurse practitioners.
      CONCLUSIONS: Neonatal nurse practitioners underestimate the incidence of
      metabolic bone disease. Parenteral calcium and phosphorous are given but in
      quantities that differ from the recommended ratio. Most neonatal nurse
      practitioners use formulas made for premature infants and add powdered fortifier
      to expressed breast milk. Although physical therapy is prescribed, more research
      on its effect on bone mineralization is warranted before this practice is
      recommended without reservation.

PMID- 9170594
TI  - Stressful events among pregnant Salvadoran women: a cross-cultural comparison.
AB  - OBJECTIVE: To compare stressful events, including violent episodes, experienced
      by pregnant Salvadoran women with those experienced by two other groups of low
      income, pregnant women living in the United States (non-Salvadoran Hispanics and
      non-Hispanics) and to examine the association between episodes of violence and
      drug or alcohol use among the three groups. DESIGN: Comparative, descriptive
      study. SETTING: Public health prenatal clinics. PARTICIPANTS: One hundred four
      Salvadoran, 69 non-Salvadoran Hispanic, and 187 non-Hispanic pregnant women. MAIN
      OUTCOME MEASURES: Difficult Life Circumstances (DLC) scale and psychosocial
      history assessment. RESULTS: Statistically significant differences were found
      among the three groups in total DLC scores, F(2, 357) = 14.98, p < .001; reported
      episodes of violence, F(2, 357 = 17.82, p < .001; and drug or alcohol use, F(2,
      357) = 6.33, p < .001. A significant difference was found to the extent that
      alcohol or drug use accounted for the variance in violence among the three
      groups, F(3, 360) = 6.28, p < .001. CONCLUSIONS: Cross-cultural comparisons
      revealed group differences in the number of stressful events, including episodes
      of violence and alcohol or drug use.

PMID- 9170595
TI  - Comparison of continuous versus intermittent sucking in very-low-birth-weight
      infants.
AB  - OBJECTIVE: To examine the effects of continuous and intermittent sucking on
      breathing and sucking during oral feedings in very-low-birth-weight infants.
      DESIGN: A quasi-experimental, within-subjects design with random assignment.
      Infants were observed twice in 1 day, once with a nasogastric tube and once
      without, in random order. SETTING: A Midwestern university-affiliated tertiary
      neonatal medical center. PARTICIPANTS: Eighteen very-low-birth-weight infants
      without severe neurologic problems or physical anomalies. On the day of the
      study, postnatal days were 17-82 days (M = 47.7, SD = +/- 19.3). INTERVENTIONS:
      Continuous sucking and intermittent sucking periods. MAIN OUTCOME MEASURES:
      Breathing parameters from prefeed to continuous sucking, and intermittent sucking
      to postfeed periods; and sucking parameters from continuous sucking to
      intermittent sucking were examined. RESULTS: Continuous sucking had more
      detrimental effects on infants' breathing (p < .05), with stronger sucking (p <
      .05) and more formula milk intake (p < .05) than intermittent sucking. Different
      patterns of change between continuous sucking and intermittent sucking indicated
      that continuous sucking affected breathing, oxygenation, and sucking more than
      did intermittent sucking. CONCLUSIONS: Nurses who feed very-low-birth-weight
      infants should learn to observe different sucking periods and breathing pauses
      during continuous sucking periods, particularly during the 1st minute of bottle
      feeding.

PMID- 9170596
TI  - Patient-focused models of care.
AB  - The structure and the process for delivering patient care will experience major
      changes during the next decade. Most hospitals have tried different alternatives,
      including restructuring, re-engineering, redesign, and the return to patient
      focused care. Staffing strategies may successfully move nurses from total patient
      care to delegated, shared accountability. During their short stays, new parents
      and their neonates receive streamlined, intensely focused care from cross-trained
      workers in a patient-focused care environment. Each interaction becomes a
      meaningful and educational one, with the focal point being the mother and the
      family.

PMID- 9170597
TI  - Case management and clinical paths: strategies to support the perinatal
      experience.
AB  - The needs of the perinatal client population and the current health care
      environment necessitate exceptionally well coordinated care throughout the entire
      episode. This is especially true of individuals who have complex problems,
      including pathophysiology, psychosocial, and economic issues. Case management
      enhances care coordination activities for individuals with complex issues.
      Clinical paths support the needs of the usual perinatal client. These two
      strategies have demonstrated effectiveness in supporting the coordination and
      management of care of perinatal clients.

PMID- 9170598
TI  - Use of accelerating clinical improvement in reorganization of care: the Dartmouth
      Hitchcock Medical Center experience.
AB  - Accelerating clinical improvement is a unique strategic method for accelerating
      the rate and effectiveness of improvements in strategically important clinical
      services. It promotes real reduction in the cost of service while preserving the
      quality and value within the system. Based on the components of process, value,
      benchmarking, change, and learning, the method can be used in any system or
      setting to produce value-driven change. Accelerating clinical improvement is
      being used within the Obstetrical Department of Dartmouth-Hitchcock Medical
      Center to decrease postpartum length of stay for families with spontaneous
      vaginal delivery. Familiarity with the method led to additional and ongoing
      improvements in the system. This method is important for nurses because it is
      continuous, multidisciplinary, addresses values of concern to families and
      providers, and is easily incorporated by nurse providers in any clinical setting.

PMID- 9170599
TI  - Outcomes management in women's health.
AB  - Outcomes management uses a quality and research approach to reducing costs in
      health care. Populations may be targeted for high volumes or their potential for
      cost savings. Outcomes are identified and measured through data collection and
      analysis. System and care processes that drive these outcomes are analyzed.
      Tenets related to outcomes management include questioning practice,
      administrative and physician involvement; recognizing that change is necessary;
      accepting uncontrollable factors; and valuing the outcomes management process.
      Resources necessary for managing outcomes include the use of collaborative
      practice teams, outcomes assessment, information systems, and educational support
      services. The women's health population can benefit from an outcomes management
      effort by improving and standardizing care for mothers and infants across the
      continuum. There is the opportunity to affect the wellness of this population
      even before the pregnancy occurs.

PMID- 9170600
TI  - [Single-dose toxicity studies of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl
      2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a
      novel drug for urinary frequency and incontinence, in mice, rats and dogs].
AB  - Comparative single-dose toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut
      2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS
      21), a new drug for the treatment of urinary frequency and incontinence, were
      conducted in ddY mice and Sprague-Dawley rats after
      oral(p.o.),intraperitoneal(i.p.) and subcutaneous(s.c.) administration, and in
      Beagle dogs after p.o. administration. The p.o. LD50 values of NS-21 were 852 and
      1167 mg/kg for male and female mice, 2839 and 1739 mg/kg for male and female
      rats, respectively. The i.p. LD50 values were 324 and 390 mg/kg for male and
      female mice, and 423 and 359 mg/kg for male and female rats, respectively. No
      death occurred in mice and rats at doses up to s.c. 5000 mg/kg. Minimum lethal
      dose for dogs could not be determined because of vomiting. Mydriasis was noted in
      all three species tested without regard to administration route. In addition,
      decreased spontaneous locomotor activity, prone or lateral position, hypopnea,
      hypothemia, ataxic gait, twitch and clonic convulsion were observed in mice and
      rats after p.o. and i.p. administration. In rats, salivation was observed after
      p.o. administration and lacrimation was observed after p.o. and i.p.
      administration. After s.c. administration, scab formation at the site of
      injection was observed in mice and rats. In dogs, vomiting, hyperemia of both
      conjunctiva and oral mucosa, prone position, tremor and clonic convulsion were
      observed after p.o. administration. Body weight was decreased or its gain was
      suppressed in mice and rats without regard to administration route. Body weight
      and food consumption were decreased in dogs after p.o. administration.
      Pathological examination showed congestion of lung in dead mice and rats after
      p.o. and i.p. administration. Distention of small intestine was observed in dead
      mice and rats after p.o. administration and in sacrificed rats after p.o.
      administration. Adhesion between the abdominal organs was observed in sacrificed
      mice and rats after i.p. administration. Thymic atrophy associated with a
      decrease in its organ weight was observed in dogs after p.o. administration.

PMID- 9170601
TI  - [Intraperitoneal single-dose toxicity studies of active metabolite, optical
      isomers, hydrolysis products and bi-product of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in
      mice].
AB  - NS-21, (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2
      phenylacetate monohydrochloride monohydrate, is a new drug for the treatment of
      urinary frequency and incontinence. To evaluate acute toxicities of its related
      compounds including the optical isomers of NS-21 ((S)NS-21 and (R)NS-21), the
      active metabolite of NS-21 ((R/S)RCC-36), the optical isomers of (R/S)RCC-36
      ((S)RCC-36 and (R)RCC-36), the hydrolysis products of NS-21 (RCC-32 and RCC-38)
      and the bi-product of NS-21 (RCC-66), single-dose intraperitoneal toxicity
      studies were conducted in ddY mice. The LD50 values of these compounds in male
      and female mice were as follows: 199 and 184 mg/kg for (S)NS-21, 261 and 240
      mg/kg for (R)NS-21, 74 and 100-150 mg/kg for (R/S)RCC-36, 93 mg/kg for (S)RCC-36
      in both sexes, 83 and 104 mg/kg for (R)RCC-36, higher than 510 mg/kg for RCC-32
      in both sexes, 340-510 mg/kg for RCC-38 in both sexes, and 1000-2000 mg/kg for
      RCC-66 in both sexes, respectively. The clinical signs included decreased
      spontaneous locomotor activity, prone or lateral position, ataxic gait, clonic
      convulsion, hypopnea, hypothermia, pale skin, mydriasis, abdominal distention and
      unkempt fur for (S)NS-21, (R)NS-21, (R/S)RCC-36, (S)RCC-36 and (R)RCC-36,
      decreased spontaneous locomotor activity, prone position, ataxic gait, clonic
      convulsion, tail elevation and hypopnea for RCC-32 and RCC-38, and decreased
      spontaneous locomotor activity and unkempt fur for RCC-66. Body weight was
      decreased or its gain was suppressed for every compound examined. Pathological
      examination of the dead mice showed atrophy of the thymus and spleen, intestinal
      distention with the retention of dark red contents, white spots or white
      materials in the abdominal fatty tissue for (S)NS-21, (R)NS-21, (R/S)RCC-36,
      (S)RCC-36, (R)RCC-36 and RCC-66, but no treatment related change for RCC-32 and
      RCC-38. Adhesion between the abdominal organs was observed in survivors treated
      with (S)NS-21, (R)NS-21, (S)RCC-36, (R)RCC-36, RCC-32 and RCC-66.

PMID- 9170602
TI  - [A 13-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in rats
      followed by a 5-week recovery test].
AB  - A 13-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in Sprague-Dawley rats. Male and female rats were
      given the drug orally for 13 weeks at doses of 0 (control), 6, 30, 150 and 750
      mg/kg. After discontinuation of the treatment, a 5-week recovery test was also
      conducted at doses of 0, 30, 150 and 750 mg/kg. Nine cases of death occurred in
      the 750 mg/kg group. Main pathological findings in these cases were congestion
      and edema in lung. Mydriasis, salivation, lacrimation and a decrease in body
      weight or a suppression of its weight gain were seen in the 30 mg/kg group and
      over. Piloerection and an increase in water consumption were seen in the 150 and
      750 mg/kg groups. In addition, a decrease in spontaneous locomotor activity,
      abdominal distention, unkempt fur, soft stool, diarrhea and decreases in feces
      and food consumption were seen in the 750 mg/kg group. Ophthalmologic examination
      confirmed mydriasis and lacrimation in the 30 mg/kg group and over. Urinalysis
      showed decreases in Na+ and K+ excretions in the 30 mg/kg group and over, an
      increase in urinary protein in the 150 and 750 mg/kg groups, and a decrease in
      urine volume in the 750 mg/kg group. Hematological examination showed decreases
      in hemoglobin and hematocrit in the 150 and 750 mg/kg groups, and a decrease in
      lymphocytes in the 750 mg/kg group. Blood chemical examination showed an increase
      in total protein in the 30 mg/kg group and over, a decrease in triglyceride in
      the 150 and 750 mg/kg groups, and an increase in BUN in the 750 mg/kg group.
      Pathological examination disclosed hepatocellular hypertrophy caused by
      hyperplasia of smooth-ER in the 30 mg/kg group and over, and a decrease in number
      of glycogen granules in the 150 and 750 mg/kg groups. Stimulated thyroid
      follicles were seen in the 30 mg/kg group and over. Increases in incidence and
      severity of chronic progressive nephropathy were observed in the 150 and 750
      mg/kg groups. Ultrastructual features of the renal lesions were swelling and foot
      process loss of the glomerular epithelial cells, absorption droplets in the
      glomerular epithelial cells, increase of lysosomes in the proximal tubular cells
      and hyaline casts in the tubular lumen. Adrenocortical hypertrophy was seen in
      the 150 and 750 mg/kg groups. In the 750 mg/kg group, a decrease of hematopoietic
      tissue in bone marrow and thymic and testicular tubular atrophy were observed.
      The recovery test showed that the above-mentioned changes were satisfactorily
      reversible or the degree and frequency of these changes were lowered. No
      treatment-related effects were seen in the 6 mg/kg group. These results show that
      the NOAEL (no observed adverse effect level) of NS-21 is 6 mg/kg for 13-week oral
      toxicity in rats.

PMID- 9170603
TI  - [A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in rats
      followed by a 9-week recovery test].
AB  - A 26-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1, 1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in Sprague-Dawley rats. Male and female rats were
      given the drug orally for 26 weeks at doses of 0 (control), 5, 50 and 500 mg/kg.
      After discontinuation of the treatment, a 9-week recovery test was also
      conducted. Two cases of death occurred in the 500 mg/kg group. Mydriasis,
      salivation and lacrimation were seen in the 50 and 500 mg/kg groups. Alopecia, a
      suppression of body weight gain and an increase in water consumption were seen in
      the 500 mg/kg group. Food consumption measurement showed no abnormalities
      attributable to the treatment. Ophthalmologic examination confirmed mydriasis in
      the 50 and 500 mg/kg groups. Urinalysis showed an increase in urine volume in the
      50 and 500 mg/kg groups, and an increase in urinary protein and decreases in Na+,
      K+ and Cl- excretions in the 500 mg/kg group. Hematological examination showed
      decreases in hemoglobin, hematocrit, MCV, MCH, MCHC and lymphocytes in the 500
      mg/kg group. Blood chemical examination showed increases in total cholesterol,
      phospholipid and total protein and decreases in glucose, triglyceride, free T3
      and T4 in the 500 mg/kg group. Measurements of liver drug-metabolizing enzymes
      showed an increase in T4UDP-GT activity in the 50 and 500 mg/kg groups, and an
      increase in cytochrome P-450 in the 500 mg/kg group. Pathological examination
      disclosed hepatocellular hypertrophy caused by hyperplasia of smooth-ER in the 50
      and 500 mg/kg groups, and a decrease in number of glycogen granules in the 500
      mg/kg group. Stimulated thyroid follicles were seen in the 50 and 500 mg/kg
      groups. Increases in incidence and severity of chronic progressive nephropathy
      were also observed in the 500 mg/kg group. In this dose group, adrenocortical
      hypertrophy was also observed. The recovery test showed that the above-mentioned
      changes were satisfactorily reversible. The serum concentrations of NS-21 and its
      active metabolite, RCC-36, in the treated groups were increased in a dose
      dependent manner. No treatment-related effects were seen in the 5 mg/kg group.
      These results show that the NOAEL (no observed adverse effect level) of NS-21 is
      5 mg/kg for 26-week oral toxicity in rats.

PMID- 9170604
TI  - [Oral single-dose and 13-week repeat-dose toxicity studies of RCC-36, the active
      metabolite of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2
      hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for
      urinary frequency and incontinence, in rats].
AB  - Oral single-dose and 13-week repeat-dose toxicity studies of (+/-)-4-ethylamino
      1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate
      monohydrochloride (RCC-36), an active metabolite of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, were conducted in male and female Sprague-Dawley rats. In the
      single-dose toxicity study, rats were given the drug at doses of 0 (control),
      400, 600, 900, 1350 and 2030 mg/kg. In the 13-week repeat-dose toxicity study,
      rats were given the drug for 13 weeks at doses of 0 (control), 3, 30 and 300
      mg/kg. After discontinuation of the treatment, a 5-week recovery test was also
      conducted. In the single-dose toxicity study, death occurred in the 600 mg/kg
      group and over, and LD50 values were 735 mg/kg in both sexes. The major clinical
      signs observed following the administration of this drug were mydriasis,
      salivation, decreased spontaneous locomotor activity, ataxic gait, lacrimation
      and urorrhea in the 400 mg/kg group and over, hypopnea and soft feces in the 600
      mg/kg group and over. In addition, prone or lateral position and tonic or clonic
      convulsion were observed in the dead animals. Rats showed a decrease in body
      weight or a suppression of its weight gain in the 400 mg/kg group and over.
      Macroscopic findings in the dead animals were congestion in lung and retention of
      foamy mucinous fluid in trachea. The animals alive showed no abnormalities
      attributable to the treatment. In the 13-week repeat-dose toxicity study, 13
      cases of death occurred in the 300 mg/kg group. Main pathological findings in
      these cases were congestion and edema in lung. Mydriasis was seen in the 30 mg/kg
      group and over. Lacrimation, salivation, wheezing, emaciation [corrected] wasting
      and unkempt fur were seen in the 300 mg/kg. A suppression of body weight gain and
      a decrease in food consumption were observed in the 300 mg/kg group. An increase
      in water consumption was seen in the 30 and 300 mg/kg groups. Ophthalmologic
      examination confirmed the mydriasis in the 30 mg/kg group and over. Urinalysis
      showed an increase in urine volume and a decrease in Na+ excretion in the 30 and
      300 mg/kg groups and decreases in K+ and Cl- excretions in the 300 mg/kg group.
      Hematological examination showed decreases in hemoglobin, hematocrit, MCV and
      MCH, and an increase in MCHC in the 300 mg/kg group. Blood chemical examination
      showed decreases in triglyceride and glucose, and an increase in total protein in
      the 300 mg/kg group. Pathological examination disclosed hepatocellular
      hypertrophy associated with hyperplasia of smooth-ER, a decrease in number of
      glycogen granules and an increase in number of lipofuscin in the 300 mg/kg group.
      Stimulated thyroid follicles were seen in the 300 mg/kg/group. In kidney, an
      increase in number of hyaline droplets in the proximal tubular epithelium, in
      which lysosomes and dense bodies were increased, was observed in the 300 mg/kg
      group. Dense bodies were increased also in the glomerular epithelium. In this
      dose group, adrenocortical hypertrophy was also observed. The recovery test
      showed that the above-mentioned changes were satisfactorily reversible or the
      degree and frequency of these changes were lowered. No treatment-related effects
      were seen in the 3 mg/kg group. These results show that the NOAEL (no observed
      adverse effect level) of RCC-36 is 3 mg/kg for 13-week oral toxicity in rats.

PMID- 9170605
TI  - [A 13-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in dogs
      followed by a 5-week recovery test].
AB  - A 13-week oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in beagle dogs. Male and female dogs were given the
      drug orally for 13 weeks at doses of 0 (control), 5, 25 and 125 mg/kg. After
      discontinuation of the treatment, a 5-week recovery test was also conducted. No
      effects related to the treatment were observed on survival. Mydriasis and a
      decrease in body weight or a suppression of its weight gain were seen in the 25
      and 125 mg/kg groups. Vomiting, salivation and a decrease in food consumption
      were seen in the 125 mg/kg group. Ophthalmologic examination confirmed the
      mydriasis in the 125 mg/kg group. Electrocardiographic examination and urinalysis
      showed no abnormalities attributable to the treatment. Hematological examination
      showed an increase in number of platelets in the 125 mg/kg group. Blood chemical
      examination revealed increases in GPT and ALP and a decrease in albumin in the 25
      and 125 mg/kg groups, and an increase in triglyceride in the 125 mg/kg group.
      Pathological examination disclosed hepatocellular hypertrophy in the 125 mg/kg
      group, hyperplasia of smooth-ER and concentric lamellar bodies derived from the
      smooth-ER, and bile pigments in the bile capillary, hepatocyte and stellate cells
      of Kupffer in the 25 and 125 mg/kg groups. Megakaryocytes in mesenteric lymph
      node were observed in the 25 and 125 mg/kg groups. The recovery test showed that
      the above-mentioned changes were satisfactorily reversible or the degree and
      frequency of these changes were lowered. No treatment-related effects were seen
      in the 5 mg/kg group. These results show that the NOAEL (no observed adverse
      effect level) of NS-21 is 5 mg/kg for 13-week oral toxicity in dogs.

PMID- 9170606
TI  - [A 12-month oral repeated dose toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in dogs
      followed by a 2-month recovery test].
AB  - A 12-month oral repeated dose toxicity study of (+/-)-4-diethylamino-1, 1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in beagle dogs. Male and female dogs were given the
      drug orally for 12 months at doses of 0 (control), 3, 17.5 and 100 mg/kg. After
      discontinuation of the treatment, a 2-month recovery test was also conducted. No
      effects related to the treatment were observed on survival and water consumption.
      Mydriasis, vomiting and a decrease in body weight or a suppression of its weight
      gain were seen in the 17.5 and 100 mg/kg groups. Salivation and a decrease in
      food consumption were seen in the 100 mg/kg group. Ophthalmologic examination
      confirmed the mydriasis in the 17.5 and 100 mg/kg groups. Electrocardiographic
      and hematological examinations and urinalysis showed no abnormalities
      attributable to the treatment. Blood chemical examination revealed increases in
      GPT and ALP in the 17.5 and 100 mg/kg groups, increases in GOT and triglyceride
      and a decrease in total protein in the 100 mg/kg group. Pathological examination
      disclosed hepatocellular hypertrophy and concentric lamellar bodies derived from
      the smooth-ER in the 100 mg/kg group, and hyperplasia of smooth-ER, an increase
      in number of lysosomes and bile pigments in the bile capillary, hepatocyte and
      stellate cells of Kupffer in the 17.5 and 100 mg/kg groups. The recovery test
      showed that the above-mentioned changes were satisfactorily reversible or the
      degree and frequency of these changes were lowered. The serum concentrations of
      NS-21 and its active metabolite. RCC-36, in the treated groups were increased in
      a dose-dependent manner. No treatment-related effects were seen in the 3 mg/kg
      group. These results show that the NOAEL (no observed adverse effect level) of NS
      21 is 3 mg/kg for 12-month oral toxicity in dogs.

PMID- 9170607
TI  - [Toxicokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2
      hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for
      urinary frequency and incontinence, in mice and rats during 13-week dietary
      administration].
AB  - Toxicokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2
      hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a new drug for the
      treatment of urinary frequency and incontinence, were studied in mice and rats
      during a 13-week dietary administration to determine the toxicokinetic profiles
      of NS-21 and its active metabolite (+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride (RCC-36) in dietary
      carcinogenicity studies. Male and female mice were given the drug in the diet at
      doses of 0(control), 30, 100 and 300 mg/kg/day, and male and female rats were
      given the drug at doses of 0(control), 10, 30 and 100 mg/kg/day. The chosen doses
      and means of administration were identical to those of a 78-week dietary
      carcinogenicity study in mice and 2-year dietary carcinogenicity study in rats.
      The plasma concentrations were measured on the first and the last day of the
      administration. For every treatment period, the plasma concentrations of NS-21
      and RCC-36 increased with dose in mice and rats. The sum of the area under the
      concentration-time curve(AUC) of NS-21 and RCC-36 was 2694 to 8614 ng.hr/ml in
      the maximum dose of mice, and 2232 to 3593 ng.hr/ml in the maximum dose of rats
      through the administration period. These results show that, when compared with
      therapeutic dose in humans(682 ng.hr/ml at 10 mg/body/day), the total maximal
      exposure to NS-21 and RCC-36 in the earlier dietary carcinogenicity studies were
      estimated to be 4 to 13 times higher in mice, and 3 to 5 times higher in rats.

PMID- 9170608
TI  - [The mechanism of increased thyroidal function caused by (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence,
      administration in rats].
AB  - A study was conducted to elucidate the mechanism of the increased thyroidal
      function caused by oral administration of (+/-)-4-diethylamino-1, 1-dimethylbut-2
      yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS
      21), a new drug for the treatment of urinary frequency and incontinence, in rats.
      Rats were given 500 mg/kg of NS-21 orally for 13 weeks. Rats were also given 500
      mg/kg of the drug and 15 micrograms/animal of thyroxine (T4) in order to assess
      the influence of T4 treatment. NS-21 caused decreases in both total and free T4
      and increases in TSH and thyroxine uridine diphosphate glucuronyltransferase
      (T4UDP-GT). Morphological examination of thyroid gland revealed stimulated
      follicles indicating heightened thyroidal function. The treatment of T4 inhibited
      the stimulating effect of NS-21 on thyroid gland. These results show that the
      administration of NS-21 caused induction of T4UDP-GT, which resulted in a
      compensatory stimulation of the thyroidal function by the increased secretion of
      pituitary TSH in response to increased blood thyroid hormone metabolism.

PMID- 9170609
TI  - [Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence (1).
      Fertility study in rats by oral administration].
AB  - Fertility and developmental toxicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in Crl:CD rats. Male rats were given NS-21 orally
      from 60 days before mating to the day of necropsy, and female rats were given NS
      21 orally from 14 days before mating to day 7 of pregnancy. The dose levels for
      both males and females were 0 (control), 2, 30 and 500 mg/kg. On day 20 of
      pregnancy, the females were sacrificed and their fetuses examined. At the 500
      mg/kg dosage level, one male and one female died. Salivation and dilated pupils
      occurred at the 30 and 500 mg/kg dosage levels, and rales occurred at 500 mg/kg.
      Body weights and food consumption were decreased, and water consumption was
      increased in both males and females at the 500 mg/kg dosage level. Decreases in
      the numbers of corpora lutea and implantations per litter and a lower number of
      live fetuses per litter were found at the 500 mg/kg dosage level. However, the
      incidence and number of postimplantation loss per litter were comparable among
      the treatment and control groups. These results demonstrate that the NOAEL (no
      observed adverse effect level) of NS-21 is 2 mg/kg for general toxicity in
      parental animals, and 30 mg/kg for reproductive function of the parent animals
      and for embryo-fetal development.

PMID- 9170610
TI  - [Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence (2).
      Teratogenicity study in rats by oral administration].
AB  - A study of teratogenicity and developmental toxicity of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a new drug for the treatment of urinary frequency and
      incontinence, was conducted in Crl:CD rats. Female rats were given NS-21 orally
      at dose levels of 0 (control), 2, 25 and 300 mg/kg from day 7 to day 17 of
      pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of
      pregnancy for examination of their fetuses, and the remaining pregnant rats
      (twenty-three per dose level) were allowed to deliver naturally for postnatal
      examination of their offspring. At the 300 mg/kg dosage level, rales, partially
      closed eyes and reduced activity were observed in pregnant rats. Decreases in
      body weight gain, food consumption and water consumption were observed in the
      dams at the 300 mg/kg dosage level. Fetal body weights were decreased at the 300
      mg/kg dosage level. The drug never altered the numbers of corpora lutea and
      implantations, fetal mortality, the number of live fetuses, sex ratio, placental
      weight, and external, visceral and skeletal development of fetuses. NS-21 did not
      affect the delivery of dams, the number of live newborns, birth index, body
      weight or survival index. Nor did NS-21 have any adverse effect on the postnatal
      development of the offspring, including physical and functional development,
      emotionality, motor activity, learning ability and reproductive performance.
      These results demonstrate that the NOAEL (no observed adverse effect level) of NS
      21 is 25 mg/kg for general toxicity in mother animals. 300 mg/kg for reproductive
      function in mother animal and 25 mg/kg for developmental toxicity.

PMID- 9170611
TI  - [Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence (3).
      Teratogenicity study in rabbits by oral administration].
AB  - A study of the effect of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new
      drug for the treatment of urinary frequency and incontinence, was conducted in
      New Zealand White rabbits during the period of fetal organogenesis. Female
      rabbits were given NS-21 orally at dose levels of 0 (control), 2, 10 and 50 mg/kg
      from day 6 to day 18 of pregnancy. Female rabbits were sacrificed on day 29 of
      pregnancy for examination of their fetuses. Five does in the 10 mg/kg dosage
      group and one doe in the 50 mg/kg dosage group died or were sacrificed in
      moribund condition. Two does in the control group died. Lacrimation and
      convulsion were observed in the 10 and 50 mg/kg groups, and no or soft stool was
      observed in the 50 mg/kg dosage group. Body weight gain, food and water
      consumptions were decreased in the 50 mg/kg dosage group. There were no effects
      of NS-21 in necropsy findings at cesarean sections in does at any dosage level.
      Developmental toxicity of fetuses was not apparent at any dosage level. These
      results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is
      2 mg/kg for maternal toxicity and 50 mg/kg for fetal toxicity.

PMID- 9170612
TI  - [Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate(NS-21), a novel drug for urinary frequency and incontinence (4).
      Perinatal and postnatal study in rats by oral administration].
AB  - A study of the effect of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new
      drug for the treatment of urinary frequency and incontinence, was conducted in
      Crl:CD rats during the perinatal and lactational periods. Female rats(thirty
      three per dose level) were given NS-21 orally at dose levels of 0 (control), 2,
      25 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant
      rats were allowed to deliver naturally for postnatal examination of their
      offspring. At the 300 mg/kg dosage level, reduced activity, salivation and rales
      were observed in dams, and five dams died. Decreases in body weight gain, food
      consumption and water consumption were also observed in the dams at the 300
      mg/kg. The number of remaining implantation sites was increased at 300 mg/kg,
      indicating fetal mortality. The number of live newborns, birth index and survival
      index at the birth were decreased at the 300 mg/kg dosage level. Reduced
      activity, paleness in color and/or discoloration were observed for many pups at
      the 300 mg/kg on lactation day 0. Body weights of male and female offspring at
      the birth were also decreased at the 300 mg/kg dosage group. Survival index at
      the 4 days was decreased at the 300 mg/kg dosage level. Body weight gains of male
      and female offspring were decreased at the 300 mg/kg during the lactational
      period and after weaning. NS-21 did not affect the postnatal development of the
      offspring, including physical and functional development, motor activity,
      emotionality, learning ability and reproductive performance. These results
      demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 25
      mg/kg for general toxicity and reproductive function in mother rats and 25 mg/kg
      for developmental toxicity of their offspring.

PMID- 9170613
TI  - [Mutagenicity studies of (+/-)-4-diethylamino-1,1,-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a
      novel drug for urinary frequency and incontinence].
AB  - The mutagenicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2
      hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the
      treatment of urinary frequency and incontinence, was investigated by the reverse
      mutation test in bacteria, the chromosome aberration test in vitro, and the
      micronucleus test in mice. The reverse mutation test was performed at a dose from
      31.3 to 4000 micrograms/plate, at which dose cell killing was observed, using
      Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli
      WP2uvrA. NS-21 did not increase revertant colonies significantly in any of the
      test strains with or without metabolic activation system (S9 mix). The chromosome
      aberration test was carried out at a dose from 3.75 to 140 micrograms/ml, at
      which dose more than 50% cell proliferation was inhibited, using cultured Chinese
      hamster lung cells (CHL/IU). No significant increases of the frequencies of cells
      with chromosome aberrations were observed with or without S9 mix. The
      micronucleus test was conducted in the bone marrow cells of Slc : ddY male mice.
      Mice were given NS-21 by a single oral administration at doses of 0, 43.8, 87.5,
      175, and 350 mg/kg, the geometric mean dose between the maximum tolerated dose
      and the minimum lethal dose. There were no significant increases in the
      frequencies of micronucleated polychromatic erythrocytes at any dose levels.
      These results show that NS-21 has no mutagenic activity in vitro or in vivo.

PMID- 9170614
TI  - [Mutagenicity studies of RCC-36, the active metabolite of (+/-)-4-diethylamino
      1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate
      monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and
      incontinence].
AB  - The mutagenicity of (+/-)-4-ethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2
      hydroxy-2-phenylacetate monohydrochloride (RCC-36), an active metabolite of (+/-)
      4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate
      monohydrochloride monohydrate (NS-21), was investigated by the reverse mutation
      test in bacteria, the chromosome aberration test in vitro, and the micronucleus
      test in mice. The reverse mutation test was performed at a dose range of 6.25-400
      micrograms/plate using Salmonella typhimurium TA100, TA1535, TA98, and TA1537,
      and Escherichia coli WP2uvrA. RCC-36 did not increase revertant colonies
      significantly in any of the test strains with or without metabolic activation
      system (S9 mix). The chromosome aberration test was carried out at a dose range
      of 2.5-20 micrograms/ml without S9 mix and 10-80 micrograms/ml with S9 mix using
      cultured Chinese hamster lung cells (CHL/IU). No significant increases of the
      frequencies of cells with chromosome aberrations were observed with or without S9
      mix. The micronucleus test was conducted in the bone marrow cells of Slc:ddY male
      mice. Mice were given RCC-36 by a single intraperitoneal administration at doses
      of 0, 10, 20, 40, and 80 mg/kg. There were no significant increases in the
      frequencies of micronucleated polychromatic erythrocytes at any dose levels.
      These results show that RCC-36 has no mutagenic activity in vitro or in vivo.

PMID- 9170615
TI  - Seventy-eight-week dietary carcinogenicity study of (+/-)-4-diethylamino-1,1
      dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride
      monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in
      mice.
AB  - The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new
      drug for the treatment of urinary frequency and incontinence, was assessed when
      it was administered in the diet of Charles River B6C3F1 mice for 78 weeks in
      dosages of 0, 30, 100 and 300 mg/kg/day. No drug-related effects occurred on
      survival, appearance or behavior, or occurrence, location or number of palpable
      masses. Average food consumption, food efficiency and hematologic values also
      were apparently unaffected. Statistically significantly low body weights were
      observed in the 100 and 300 mg/kg/day mice. The plasma concentrations of NS-21
      and its active metabolite, RCC-36, in the treated groups were increased in a dose
      dependent manner. Histopathological examinations disclosed midzonal
      hepatocellular vacuolization compatible with lipid vacuoles in both sexes at the
      300 mg/kg/day dose level. There were no test article-related effects on the
      incidence or type of neoplastic lesions. In conclusion, under the conditions of
      this study, no oncogenic effects were evident in B6C3F1 mice when NS-21 was
      administered in the diet in concentrations to produce an intake of up to 300
      mg/kg/day for 78 weeks.

PMID- 9170616
TI  - Two-year dietary carcinogenicity study of (+/-)-4-diethylamino-1, 1-dimethylbut-2
      yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS
      21), a novel drug for urinary frequency and incontinence, in rats.
AB  - The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new
      drug for the treatment of urinary frequency and incontinence, was assessed when
      it was administered in the diet of Charles River Fischer-344 rats for 2 years in
      dosages of 0, 10, 30 and 100 mg/kg/day. No drug-related effects occurred on
      survival, appearance or behavior, or occurrence, location or number of palpable
      masses. Food efficiency and hematologic values also were apparently unaffected.
      Statistically significantly low mean weekly body weights and average food
      consumption values were observed in the all dose groups. The plasma
      concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups
      were increased in a dose-dependent manner. Histopathological examinations
      disclosed test article-related increases in the incidence of periportal
      hypertrophy and midzonal hepatocellular vacuolization in the livers of the 100
      mg/kg/day animals. There were no test article-related effects on the incidence or
      type of neoplastic lesions. In conclusion, under the conditions of this study, no
      oncogenic effects were evident in Fischer-344 rats when NS-21 was administered in
      the diet in concentrations to produce an intake of up to 100 mg/kg/day for 2
      years.

PMID- 9170617
TI  - [Antigenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a
      novel drug for urinary frequency and incontinence].
AB  - An antigenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2
      cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new
      drug for the treatment of urinary frequency and incontinence, was conducted in
      Hartley guinea pigs and BALB/cAnN mice. The following results were obtained. No
      active systemic anaphylaxis reactions were found in guinea pigs immunized by
      subcutaneous injection of NS-21 alone or in combination with Freund's complete
      adjuvant (FCA). No 24-hr heterologous passive cutaneous anaphylaxis reactions
      were elicited in rats by sera from mice immunized by intraperitoneal injection of
      NS-21 alone or in combination with 3% aluminum hydroxide gel. No passive
      hemagglutination reactions were elicited by sera from mice immunized by
      subcutaneous injection of NS-21 in combination with FCA. These results show that
      NS-21 has no antigenicity under the present experimental conditions.

PMID- 9170618
TI  - Usefulness of 99Tcm-tetrofosmin scintimammography in palpable breast tumours.
AB  - The aim of this exploratory study was to assess the potential of discriminating
      malignant from non-malignant lesions using 99Tcm-tetrofosmin scintimammography in
      the detection of palpable breast tumours. Nine patients with palpable masses were
      studied; seven had malignant lesions and two had non-malignant lesions. All
      diagnoses were established by fine-needle aspiration (FNA) biopsy cytology. Each
      patient received 925 MBq (25 mCi) 99Tcm-tetrosfosmin intravenously. Planar prone
      views were acquired in the right lateral, left lateral and anterior positions,
      and the axillary regions were included in the field of view. Scintimammography
      showed focally increased tracer uptake in seven patients with a positive FNA
      result. The two patients with a negative FNA result showed no increased uptake.
      We suggest that 99Tcm-tetrosfosmin shows promise as a radiopharmaceutical in the
      detection and discrimination of the nature of palpable breast tumours. Larger
      studies are required to confirm these findings.

PMID- 9170619
TI  - Visualization of lung cancer with 99Tcm-tetrofosmin imaging: a comparison with
      201T1.
AB  - We evaluated the usefulness of 99Tcm-tetrofosmin imaging in lung cancer. The
      study sample comprised 46 patients with lung cancer. Single photon emission
      tomography was conducted after the intravenous injection of 740 MBq 99Tcm
      tetrofosmin and 111 MBq 201T1-chloride. We obtained an uptake ratio (counts per
      pixel in the lesion/counts per pixel in contralateral normal lung) for each scan
      to evaluate the degree of uptake in the tumour. Our results demonstrate that
      89.1% of the primary lung cancers were visualized by 99Tcm-tetrofosmin and 95.7%
      by 201T1. The difference between the 201T1 uptake ratio and the 99Tcm-tetrofosmin
      uptake ratio was significantly greater in squamous cell carcinomas than small
      cell carcinomas (P < 0.01) and tended to be greater in squamous cell carcinomas
      than adenocarcinomas (P = 0.093). This study has indicated that 99Tcm
      tetrofosmin, like 201T1, is a highly effective agent in the delineation of lung
      cancer. The difference between the 99Tcm-tetrofosmin and 201T1 uptake ratios
      might provide further information regarding the histological type of lung cancer.

PMID- 9170620
TI  - Effect of administered activity on precision in the assessment of renal function
      using gamma camera renography.
AB  - Split and total renal function are commonly assessed from time-activity curves
      obtained from gamma camera renography with 99Tcm-diethylenetriamine pentaacetate
      (99Tcm-DTPA) and 99Tcm-mercaptoacetyl-triglycine (99Tcm-MAG3). The impact of the
      statistical noise associated with these curves on the total precision in split
      and total renal function impairment was studied at different levels of
      administered activity by simulation. The simulation consisted of generated time
      activity curves, with statistical noise corresponding to the administration of 10
      400 MBq 99Tcm-DTPA or 7.5-150 MBq 99Tcm-MAG3. Our results indicate that the error
      induced by statistical noise in split renal function calculations is generally
      very low (< 3% at 100 MBq 99Tcm-DTPA or 75 MBq 99Tcm-MAG3) and only affects
      precision slightly in calculations at 45-50 MBq 99Tcm or more. Similar results
      were obtained for precision in GFR calculations, where the total error increased
      from 12.3% at 100 MBq 99Tcm-DTPA to 12.8% at 50 MBq, but decreased to 12.0% at
      400 MBq. Consequently, statistical noise has a minor effect on the precision in
      split and total renal function calculations at commonly used activity levels when
      it is reduced to approximately 50 MBq.

PMID- 9170621
TI  - Reproducibility of a single-sample method for 99Tcm-MAG3 clearance under clinical
      conditions.
AB  - The aim of this study was to assess the intra-individual reproducibility of 99Tcm
      mercaptoacetyltriglycine (99Tcm-MAG3) clearance in routine clinical practice in
      various circumstances using a single-sample method. Three groups of 30 patients
      each were enrolled in the study. Investigations were repeated on the same day
      with two different levels of activity (group A), within 1 week (group B), or
      after 1 year (group C). Blood samples were taken after 20 and 25 min and
      clearance values were averaged to minimize incidental errors after calculation
      according to the formula proposed by Bubeck et al. For clearance estimation on
      the same day, time-dependent background correction for residual activity was
      carried out. The mean difference was -2.0%, +6.0% and -1.5% (S.D. = 6.3%, 15.7%
      and 11.7%) for groups A, B and C respectively, taking into account values > 100
      ml min-1 only. We demonstrated that 99Tcm-MAG3 clearance is highly reproducible
      under the same conditions. However, a repeat clearance measurement on a separate
      day revealed large differences. Therefore, in follow-up studies for evaluation of
      changing kidney function (e.g. surgery or chemotherapy), differences should
      exceed 30% (i.e. 2 S.D. of group B) to be statistically significant.

PMID- 9170622
TI  - Computer-generated attenuation correction does not improve the accuracy of
      myocardial perfusion scintigraphy.
AB  - A short study was performed to determine if it is possible to increase the
      accuracy of thallium-201 (201T1) single photon emission tomographic myocardial
      perfusion imaging using computer-generated ('Chang') attenuation correction. The
      stress and rest myocardial perfusion studies from 22 patients with suspected or
      known ischaemic heart disease were reconstructed with and without "Chang'
      attenuation correction. For all patients, the scintigraphy results were compared
      with those of coronary angiography. Attenuation correction improved the accuracy
      of 201T1 myocardial perfusion imaging for defining myocardial ischaemia or
      infarction in 8% of coronary artery territories (23% of patients), but it was
      worse in 5% of coronary artery territories (14% of patients). These changes were
      not significant (McNemar's test). Therefore, computer-generated 'Chang'
      attenuation correction does not appear to improve the accuracy of myocardial
      perfusion scintigraphy. It is important that all techniques suggested to improve
      the accuracy of clinical images should be tested on patients before being widely
      used.

PMID- 9170623
TI  - Uptake index and stimulated salivary gland response in 99Tcm-pertechnetate
      salivary gland scintigraphy in normal subjects.
AB  - With a view to improve the diagnosis of salivary gland diseases (in particular,
      Sjogren's syndrome) associated with decreased salivary gland function and
      decreased stimulated salivary gland response, the normal range of radionuclide
      uptake function and the stimulated salivary gland response were established in 27
      subjects without any known salivary gland disease. Following injection of 99Tcm
      pertechnetate, sequential images were recorded for 40 min with oral
      administration of citric acid at 30 min. The total uptake index (TUI) was
      calculated as the sum of the background corrected count rates over the parotid
      and submandibular glands at 3 min divided by the injected dose. The TUI,
      expressed as a percentage of dose, was 0.55 +/- 0.12 (mean +/- S.D.). The
      stimulated salivary gland response (SSGR) was calculated as the difference
      between the rate constants (min-1) of monoexponential fits to the time-activity
      curves over the four salivary glands immediately after and before the
      administration of citric acid. The lower significance limit (P < 0.05) of the
      SSGR was a 2.4% decrease per min. The parameters TUI and SSGR can be used as a
      diagnostic tool in, for example, early Sjogren's syndrome.

PMID- 9170624
TI  - Scintigraphy of acute inflammatory lesions in rats with radiolabelled recombinant
      human interleukin-8.
AB  - We compared 125I-labelled recombinant human interleukin-8 (125I-IL-8) with 111In
      labelled human leukocytes (111In-WBC) and 67Ga-citrate for scintigraphic
      depiction of acute sterile inflammatory lesions in rats. Radioiodination of IL-8
      was catalysed by chloramine-T, and human leukocytes were radiolabelled with 111In
      oxine. Inflammatory lesions were induced in male rats by subcutaneous injection
      of 2% carrageenan suspension into their left hindlimbs. Twenty-four hours later,
      each rat received 1.8-3.7 MBq (50-100 microCi) of a single agent by intravenous
      injection. Sequential whole-body scintigrams were obtained between 0 and 96 h
      post-injection. Activities in the lesion-bearing and control hindlimbs were
      expressed as regional percent injected activity corrected for physical decay
      (%IA) by reference to concurrently imaged standards, and for 125I-IL-8 by direct
      tissue counting at necropsy as well. 125I-IL-8 displayed appropriate
      electrophoretic mobility, retained chemotactic and high-affinity receptor-binding
      activity in vitro, and exhibited exponentially decreasing activity in most
      tissues beginning shortly after intravenous injection. Scintigrams showed
      asymmetrically increased activity in the lesion-bearing hindlimb for all three
      agents. By scintigraphy, 125I-IL-8 activity in the lesion-bearing hindlimb
      reached a zenith 1-3 h post-injection at 4.8 +/- 0.5 %IA and decreased
      exponentially thereafter, with little change in lesioned-to-control limb ratios
      (mean L/C = 3.0 +/- 0.7) over the imaging period. By direct tissue counting,
      abscess-associated mean IL-8 activity per gram of tissue increased to four times
      that of adjacent muscle and nearly seven times that of contralateral muscle by 24
      h post-injection. Lesion-bearing hindlimb 111In-WBC activity also rose rapidly,
      reaching 4.2 +/- 0.6 %IA by scintigraphy at 3 h and an eventual plateau (maximum
      of 4.5 +/- 0.4 %IA) by 24 h. 67Ga scintigraphic activity in the lesion-bearing
      hindlimb peaked briefly at 3-6 h post-injection (9.2 +/- 0.5 %IA) and
      subsequently declined to a constant level of about 7.5 %IA. However, L/C for
      111In-WBC and for 67Ga-citrate each averaged only 1.5 +/- 0.3 over the imaging
      period, compared with a mean L/C of 1.2 +/- 0.2 for a blood pool radiotracer. We
      conclude that 125I-IL-8 is rapidly and selectively concentrated in regions of
      acute inflammation, presumably by high-affinity binding to IL-8 receptors on
      neutrophils within the inflammatory focus. Radioiodinated IL-8 offers an
      attractive alternative to 67Ga-citrate and 111In-WBC for early imaging of acute
      inflammatory lesions, and demonstrates significantly higher target-to-nontarget
      activity ratios in this model. The potential usefulness of radiolabelled IL-8 for
      clinical scintigraphy should be evaluated.

PMID- 9170625
TI  - Development of a three-dimensional computer-generated lung segment overlay chart.
AB  - Knowledge of segmental anatomy improves accuracy and precision in interpretation
      of perfusion lung studies. We report here a computer-oriented method that allows
      creation of an 'anatomic wire line diagram overlay of pulmonary segments'
      (AWLDOPS) for use as reference diagrams to more accurately localize segmental
      lung scan perfusion defects using MedImage Medview software. Superimposition of
      AWLDOPS and manipulation of the perfusion images is achieved so as to co-register
      images in size, obliquity and rotation.

PMID- 9170626
TI  - Close contact doses to children from radioactive patients.

PMID- 9170627
TI  - Thromboembolism: challenges for non-invasive diagnostic assessment.

PMID- 9170628
TI  - A diagnostic classification of problem behavior in dogs and cats.
AB  - Veterinary clinical ethology is a relatively new field in veterinary practice;
      with the development of a new discipline, problems often arise regarding
      diagnosis and the use of terminology. This article proposes a diagnostic system
      that can be applied by practitioners and researchers. The classification is
      divided into six main etiologic categories of behavior problems: (1) problems of
      a genetic origin, (2) problems caused during the animal's developmental stages,
      (3) ethogram deviations, (4) disturbed social interaction, (5) disease-related
      behavior, and (6) adaptation inabilities. Conditions may overlap, and all
      categories involved in a diagnosis should be mentioned for the sake of clarity
      and completeness.

PMID- 9170629
TI  - Canine communication.
AB  - Communication occurs when one individual, the sender, produces a signal that
      alters the behavior of another individual, the receiver. The signal can provide
      broadcast information about species and individual identity or transmitted
      information, in which the sender effects a change in the receiver's behavior. To
      reduce ambiguity, signals have evolved to be conspicuous, redundant, and
      stereotypic. These features allow communication signals to be produced by senders
      and perceived and acted upon appropriately by receivers, both conspecific and
      heterospecific. The modality of the communication signal can be visual,
      olfactory, or acoustic. Visual signals can be adjusted rapidly for response
      during interactions between individuals at close or medium range. Examples
      include displays of relative dominance or submission. Olfactory signals can be
      used for individual, sex, or group identity at close range during greetings and
      assessments of individuals. Excretory products can be used for olfactory
      communication over long distances and for long periods of time. Acoustic signals
      can be adjusted rapidly for close- and far-range communication. They do not
      persist in the environment. For dogs, communication is fundamental to maintaining
      affiliations, reducing competition, and identifying individuals. These factors
      are critical to the highly developed social behavior of dogs. In an ultimate
      sense, dogs have been selectively bred for positive interactions with humans; in
      a proximate sense, many dogs spend their lives in close social association with
      humans. For these reasons, many of the signals used by dogs in dog-dog
      communication are also used in dog-human communication. Veterinarians act as
      receivers for communication signals when greeting dogs as patients. The
      information obtained is used to assess the state of arousal and probability of
      future behavior of the dog so that handling of the animal can be facilitated. The
      goals are to minimize stress and injury, to successfully complete the treatment
      program, and to promote the health of the animal.

PMID- 9170630
TI  - Puppy socialization classes.
AB  - Setting up a puppy training program is one of the most important services
      veterinarians can offer. Puppy socialization classes aim not only to socialize
      the puppies so that they learn to interact well with children, adults, and other
      dogs, but also to teach basic obedience exercises. The classes build a strong
      bond between puppy, owner, and veterinary clinic. This article covers the
      techniques used, the structure of the classes, and outlines benefits for the dog,
      owner, veterinarian, and community.

PMID- 9170631
TI  - Assessment, management, and prognosis of canine dominance-related aggression.
AB  - Aggression directed toward owners is a common complaint, and one that causes a
      great deal of emotional conflict. Assessment and treatment of this disturbing
      behavior problem must address owner safety as well as realistic expectations for
      improvement. Relatively mild aggression may be treated with a combination of
      prevention of injury, increased structure in the home, and safe control of the
      dog, including obedience training to reward the dog for deference to the owner.
      Disproportionately severe or unpredictable aggression is less likely to respond
      to treatment. Mounting evidence exists that aggressiveness is genetically and
      neurobiologically driven. Research in other species, and early research in the
      dog, suggest that aggression may be reduced by drug therapy to modify brain
      neurochemistry. Such treatment is not a cure, however, and should be paired with
      a lifelong, systematic program of safety and control in the home.

PMID- 9170632
TI  - Social dynamics and behavior problems in multiple-dog households.
AB  - Certain behavior problems can be aggravated by the presence of conspecifics.
      Behavior problems that can occur in multiple-dog households as a result of social
      facilitation are discussed, along with behavior modification and pharmacologic
      treatments necessary to manage the problem.

PMID- 9170633
TI  - Assessment and treatment of excessive barking in the domestic dog.
AB  - Barking is a normal and common method of communication in the domestic dog, but
      it can become a problem behavior in specific circumstances. Excessive barking can
      be a mild annoyance or a severe problem, particularly if the owner is under
      pressure from other people to stop the dog's behavior. Preventive measures could
      reduce the likelihood of the behavior becoming problematic. Correctly assessing
      the motivation behind a dog's excessive barking once it becomes a problem is
      crucial to the implementation of a successful treatment regimen. Veterinarians
      should be prepared to give practical advice to clients in both instances, because
      the recommendations could improve the chance of the dog staying in the household.

PMID- 9170634
TI  - Diagnosis and treatment of destructive behavior in dogs.
AB  - Destructive behavior in dogs can be expensive for owners and life-threatening for
      dogs. The human-companion animal bond is jeopardized. A diagnostic plan should
      address both behavioral and medical causes of destructive behavior. Once a
      diagnosis has been established, a successful therapeutic plan can be formulated.
      Treatment includes modification of both behavior and environment and may
      incorporate the judicious use of psychotropic medication.

PMID- 9170635
TI  - Social behavior and aggressive problems of cats.
AB  - Cats form social groups in which individuals recognize each other, and the
      cohesiveness of the group is maintained by a variety of amicable behaviors.
      Agonistic behavior may occur between group members and between group members and
      nongroup members. Within the domestic environment, agonistic behavior may become
      a problem when it is directed at housemates or humans. Differential diagnosis and
      treatment of various problems of aggressive behavior are discussed.

PMID- 9170636
TI  - Feline inappropriate elimination.
AB  - Cases involving inappropriate elimination can be treated successfully through
      careful diagnosis, identification of causative factors, and development of an
      appropriate treatment plan. Veterinarians can provide a valuable service to their
      clients through case workups, educational information, and timely referrals.
      Normal elimination and marking behavior and causative factors involved in
      inappropriate elimination cases are reviewed. Treatments, including behavior
      modification techniques and drug therapy suggestions, also are included in this
      article.

PMID- 9170637
TI  - Sexual behavior problems in dogs and cats.
AB  - Sexual behavior problems do occur as a primary diagnosis, but excessive sexual
      behavior is a common secondary problem. Mounting occurs in almost half of dogs
      with behavior problems and 20% of cats with behavior problems.

PMID- 9170638
TI  - Using learning theory in animal behavior therapy practice.
AB  - This article reviews the principles of learning and how they can be employed in
      the scientific validation of animal behavior therapy. The nature of learned
      behavior is reviewed at a practical level. General programs for increasing and
      decreasing a behavior are described, along with guidelines for considering and
      assessing their efficacy in any given situation.

PMID- 9170639
TI  - Pharmacologic treatments for behavior problems.
AB  - Most of the future advances in therapy with behavioral medicine probably will be
      pharmacologic. Newer developments in tricyclic antidepressants, specific and
      nonspecific anxiolytics, narcotic agonist-antagonists, and benzodiazepines will
      have great relevance for veterinary medicine. As the field of behavioral medicine
      expands, its paradigm hopefully will enlarge to include combination therapy and
      the implementation of neuropharmacologic intervention as a diagnostic tool. At
      present, the veterinary practitioner can effectively aid many common behavioral
      problems, with the glaring exception of most aggressions, using extant drugs.

PMID- 9170640
TI  - Behavior problems of pet pigs.
AB  - Pigs of all kinds can be enjoyable, charming pets, but the reduced size of the
      Vietnamese potbellied pig makes it an excellent choice for a porcine pet. Their
      curious, almost childlike behavior, as well as their adaptability and ease of
      learning, can make them a real pleasure and a great challenge to keep. The author
      fears that as many as 25% to 50% of potbellied pigs are no longer in their
      original homes by 1 year of age primarily because of a high incidence of behavior
      problems. These are, in reality, "people problems," not "pet problems." The
      environmental and training requirements of the potbellied pig are more complex
      and require more understanding than those of the average dog or cat. The author's
      belief is that the potbellied pig's strong drive to be dominant is a unique
      behavioral characteristic that more people should be made aware of before
      acquiring a pet pig. With knowledge of normal pig behavior, problems can be
      avoided through proper socialization and training. If pet owners consult a
      veterinarian knowledgeable about pig behavior at the first sign of a problem,
      treatment usually can be successful.

PMID- 9170641
TI  - Ontogenetic variation in small-bodied New World primates: implications for
      patterns of reproduction and infant care.
AB  - This paper explores relations of ontogeny, life history strategies and patterns
      of infant care in 11 species of small-bodied New World monkeys. Analysis of these
      data suggests that differences in the social systems of Aotus, Callicebus,
      Saimiri, Callimico, Saguinus, Leontopithecus, Cebuella and Callithrix are closely
      tied to both the costs of reproduction and to the ontogenetic requirements of
      maturing young. In Saimiri, both rapid prenatal body weight and perinatal brain
      growth result in relatively high metabolic costs to breeding females. These
      costs, coupled with minimal nonmaternal assistance in caregiving, appear to favor
      a reproductive strategy that limits offspring production to a single birth at 2
      year intervals. In contrast, tamarins and marmosets are capable of producing
      twins twice in the same year. Prenatal investment in each offspring is relatively
      low, and the potentially high postnatal costs of nursing 2 infants are minimized
      by the evolution of a social system involving extensive extramaternal care
      giving. Cooperative infant care in callitrichins (tamarins and marmosets) serves
      to distribute the metabolic costs of infant ontogeny among several group members.
      Callimico is also characterized by a high reproductive output, with females
      capable of producing a single infant twice during the year. Infants continue to
      grow rapidly after weaning. Patterns of infant development in Callimico are
      similar to those found in tamarins and marmosets and support a close phylogenetic
      relationship among these taxa. Aotus and Callicebus are characterized by an
      alternative strategy. In these taxa, a monogamous mating system is associated
      with paternal certainty, male parental care, and provisioning of the young. The
      transfer of male energetic resources to a single offspring allows night and titi
      monkeys to maintain a comparatively short interbirth interval (1 year).
      Ecological and social factors, such as predation and feeding competition, do not
      appear to adequately explain much of the observed variation in infant development
      and preadult growth rates in these platyrrhines. Instead, reproductive strategies
      are strongly linked to ontogenetic patterns and life histories.

PMID- 9170642
TI  - Genetic relatedness and alloparental behaviour in a captive group of spider
      monkeys (Ateles geoffroyi).

PMID- 9170643
TI  - Predation on Milne-Edward's sifaka (Propithecus diadema edwardsi) by the fossa
      (Cryptoprocta ferox) in the rain forest of southeastern Madagascar.

PMID- 9170644
TI  - Daddy's girl? Anomalous social rank of a female rhesus macaque (Macaca mulatta).

PMID- 9170645
TI  - Pan paniscus and hominoid phylogeny: morphological data, molecular data and
      "total evidence'.

PMID- 9170646
TI  - Determination of selenium in feeds and premixes: collaborative study.
AB  - A total of 17 laboratories participated in a collaborative study for the
      determination of selenium in feeds and premixes using either a fluorometric or a
      continuous hydride generation atomic absorption (HGAA) method. Each collaborator
      analyzed 16 blind duplicate samples of feed and premixes from various feed
      manufacturers. The amount of Se in these materials ranged from 0.2 to 5500
      micrograms/g. Six laboratories used only the fluorometric procedure, 8
      laboratories used only the hydride generation atomic absorption procedure, and 3
      laboratories used both procedures. One laboratory in the fluorometric study and 3
      laboratories in the HGAA study were initially excluded because of invalid data.
      Poor agreement between the blind duplicates indicated probable sample interchange
      and/or dilution error. The data from 8 laboratories were submitted to statistical
      analysis, including data from 2 laboratories participating in both studies. The
      repeatability standard deviation (RSDr) for samples analyzed by the fluorometric
      procedure ranged from 5.9 to 33%, and the reproducibility standard deviation
      (RSDR) ranged from 12 to 33%. RSDr for samples analyzed by HGAA ranged from 2.8
      to 18%, and RSDR ranged from 4.0 to 36%. Both fluorometric and continuous hydride
      generation atomic absorption methods for the determination of Se in feeds and
      premixes have been adopted first action by AOAC INTERNATIONAL.

PMID- 9170647
TI  - Liquid chromatographic determination of nitrofuran residues in bovine muscle
      tissues.
AB  - A liquid chromatographic (LC) method was developed and statistically validated
      for simultaneous determination of nitrofurazone, nitrofurantoin, furazolidone,
      and furaltadone residues in bovine muscle tissues. These antimicrobial residues
      in samples stabilized at pH 6.0 were extracted with acetonitrile and purified by
      liquid-liquid partition between dichloromethane-ethyl acetate and hexane
      saturated with acetonitrile. The acetonitrile-ethyl acetate extract was
      concentrated, and drug residues were dissolved in LC mobile phase, filtered, and
      determined by LC. A C18 reversed-phase (ODS Hypersil) column at 35 degrees C, a
      mobile phase of 0.01M sodium acetate buffer (pH 4.5)-acetonitrile (70 + 30), and
      a UV/visible diode array detector at 365 nm were used. The retention times and UV
      spectra of peaks in spiked samples were compared with those of known nitrofurans.
      Limits of detection (LD) and quantitation (LQ) were 1 and 2 micrograms/kg,
      respectively. Average recoveries were 76% (range, 60-110%). Relative standard
      deviations ranged from 6 to 18% at 5 fortification levels from 1.5 to 20
      micrograms/kg). (Fortification levels for furaltadone were 3 to 40
      micrograms/kg). The method was used to analyze 350 samples per year from 1993 to
      1995.

PMID- 9170648
TI  - Liquid chromatographic determination of acriflavine and proflavine residues in
      channel catfish muscle.
AB  - A liquid chromatographic (LC) method was developed for determination of
      acriflavine (ACR) and proflavine (PRO) residues in channel catfish muscle.
      Residues were extracted with acidified methanol solution, and extracts were
      cleaned up with C18 solid-phase extraction columns. Residue concentrations were
      determined on an LC cyano column, with spectrophotometric detection at 454 nm.
      Catfish muscle was individually fortified with ACR (purified from commercial
      product) and PRO at concentrations of 5, 10, 20, 40, and 80 ppb (5 replicates per
      level). Mean recoveries from fortified muscle at each level ranged from 86 to
      95%, with relative standard deviations (RSDs) of 2.5 to 5.7%. The method was
      applied to incurred residues of ACR and PRO in muscle after waterborne exposure
      of channel catfish to commercial acriflavine (10 ppm total dye for 4 h). RSDs for
      incurred residues of ACR and PRO were in the same range as those for fortified
      muscle. Low residue concentrations (< 1% of exposure water concentration)
      suggested poor absorption of ACR and PRO in catfish.

PMID- 9170649
TI  - VIDAS enzyme-linked fluorescent immunoassay for detection of Salmonella in foods:
      collaborative study.
AB  - The VIDAS SLM method for detection of Salmonella was compared with the
      Bacteriological Analytical Manual (BAM)/AOAC culture method in a collaborative
      study. Twenty laboratories participated in the evaluation. Each laboratory tested
      one or more of 6 test products: milk chocolate, nonfat dry milk, dried whole egg,
      soy flour, ground black pepper, and ground raw turkey. No significant differences
      (P < 0.05) were observed between the 2 methods. The 2 methods were in agreement
      for 99% of 1544 samples analyzed. Of the 20 samples out of agreement, 8 were
      VIDAS SLM positive and BAM/AOAC negative, and 12 were VIDAS SLM negative and
      BAM/AOAC positive. The VIDAS SLM method for detection of Salmonella in foods has
      been adopted first action by AOAC INTERNATIONAL.

PMID- 9170650
TI  - High-sensitivity dry rehydratable film method for enumeration of coliforms in
      dairy products: collaborative study.
AB  - A dry-film coliform count plate that is inoculated with 5 mL sample was compared
      with the Violet Red Bile Agar plate method in a collaborative study by 18
      laboratories. Products analyzed were 2% milk, chocolate milk, cream, vanilla ice
      cream, cottage cheese, and cheese. Collaborators tested blind duplicate
      uninoculated samples and samples inoculated at low, medium, and high level.
      Significantly (P < 0.05) higher numbers of coliforms were recovered by the dry
      film method from 2% milk samples at the 3 inoculum levels, the chocolate milk at
      the low- and high-inoculum levels, and the cream at the high-inoculum level.
      Significantly higher counts were obtained by the agar method for cottage cheese
      samples at the low-inoculum level. The repeatability standard deviation for the
      dry-film method was significantly higher for the high-inoculum level chocolate
      milk sample and the medium-inoculum level cottage cheese. The same statistic was
      significantly higher for the agar method at all 3 inoculum levels in the 2% milk
      and the medium-inoculum level cream. The high-sensitivity dry rehydratable film
      method for enumeration of coliforms in dairy products has been adopted first
      action by AOAC INTERNATIONAL.

PMID- 9170651
TI  - Visual immunoprecipitate assay (VIP) for detection of enterohemorrhagic
      Escherichia coli (EHEC) O157:H7 in selected foods: collaborative study.
AB  - Five foods representative of a variety of food products were analyzed by the
      Visual Immunoprecipitate Assay (VIP) and the Bacteriological Analytical Manual
      (BAM) culture method for the presence of Escherichia coli O157:H7. A total of 21
      laboratories representing state and federal government agencies, as well as
      private industry, in the United States and Canada participated. Food types were
      inoculated with strains of E. coli O157:H7, with the exception of one lot of
      poultry, which was naturally contaminated. During this study, a total of 1377
      samples and controls were analyzed and confirmed, of which 508 were positive and
      867 were negative by both methods. Two samples were positive by BAM and negative
      by VIP. Because of the study design, it was not possible for the BAM method to
      produce false-negative or false-positive results. The VIP assay for detection of
      EHEC in selected foods has been adopted first action by AOAC INTERNATIONAL.

PMID- 9170652
TI  - Assurance enzyme immunoassay for detection of enterohemorrhagic Escherichia coli
      O157:H7 in selected foods: collaborative study.
AB  - Five foods types were analyzed by the Assurance EHEC (Escherichia coli O157:H7)
      enzyme immunoassay (EIA) and by the Bacteriological Analytical Manual (BAM)
      culture method. Each sample of each food type at each inoculation level was
      simultaneously analyzed by both methods. A total of 21 laboratories representing
      state and federal government agencies and private industry in the United States
      and Canada participated. Samples were inoculated with E. coli O157:H7, except for
      one lot of poultry that was naturally contaminated. A total of 1304 samples and
      controls were analyzed and confirmed, of which 473 were positive and 818 were
      negative by both methods. Thirteen samples were positive by BAM but negative by
      EIA. Because of the study design, it was not possible for the BAM method to
      produce false-negative or false-positive results. The Assurance method for
      detection of E. coli O157:H7 in selected foods has been adopted first action by
      AOAC INTERNATIONAL.

PMID- 9170653
TI  - Determination of long-life radiocesiums Cs-134 and Cs-137 in food by gamma-ray
      spectrometry: summary of collaborative study.
AB  - A collaborative study was conducted to validate a gamma-ray spectrometric method
      for determining cesium-134 and cesium-137 in foods. The Cs-134 and Cs-137
      contents are measured with a low-resolution, shielded TI-activated Nal
      scintillation detector connected to a multichannel gamma-ray spectrometer.
      Thirteen laboratories participated in the study. Participants received 8 samples
      of heather honey, milk, and mixed dried herbs, including 4 blind duplicates. The
      accuracy of mean measurements of both isotopes was in the range of 98 to 103%,
      compared with reference measurements made in one laboratory using a high
      resolution GeLi detector. Repeatability relative standard deviation (RSDr) values
      varied from 4.3 to 11.7% for 2 Cs-134 levels ranging from 121 to 337 Bq/kg and
      from 2.0 to 7.3% for 4 Cs-137 levels ranging from 210 to 1130 Bq/kg.
      Reproducibility relative standard deviation (RSDR) values ranged from 10.7 to
      14.9% for Cs-134 and from 4.1 to 7.4% for Cs-137. No outliers were identified,
      and the method worked well in the absence of "fresh" fission products. However,
      the method was less appropriate for radiocesium determinations for activity
      concentration < 100 Bq/kg at a counting time of 900 s or when Cs-137/Cs-134
      activity ratio was larger than 10. The gamma-ray method for determining Cs-134
      and Cs-137 in foods has been adopted first action by AOAC INTERNATIONAL.

PMID- 9170654
TI  - Liquid chromatographic determination of the glycoalkaloids alpha-solanine and
      alpha-chaconine in potato tubers: NMKL Interlaboratory Study. Nordic Committee on
      Food Analysis.
AB  - Twelve laboratories participated in a collaborative study to evaluate precision
      parameters of a liquid chromatographic method for analysis of the glycoalkaloids
      alpha-solanine and alpha-chaconine in potato tubers. Samples consisted of frozen
      potato tuber homogenates distributed as 3 blind duplicates and 3 split-level
      pairs. The analytical method included aqueous extraction, workup on disposable
      solid-phase extraction cartridges, and reversed-phase chromatography with
      photometric detection at 202 nm. Results for alpha-solanine and alpha-chaconine
      were received from 10 and 9 laboratories, respectively. Relative standard
      deviations for reproducibility for alpha-solanine and alpha-chaconine were
      similar, ranging from 8 to 13% in the applied concentration range of 12 to 260
      mg/kg fresh weight.

PMID- 9170655
TI  - Determination of total, saturated, and monounsaturated fats in foodstuffs by
      hydrolytic extraction and gas chromatographic quantitation: collaborative study.
AB  - Using gas chromatography (GC), 10 collaborating laboratories measured total,
      saturated, and monounsaturated fats in 8 blind duplicate pairs of foodstuffs. The
      method involves a hydrolysis/ether extraction of fat followed by quantitative GC
      analysis versus an internal standard. Calculations were designed to comply with
      federal regulations as specified in the Nutrition Labeling and Education Act of
      1990. The range of fat contents was about 1-50%. Collaborators received and
      analyzed (in triplicate) a pre-collaborative sample of known fat content as a
      practice sample. After satisfactory results were obtained, participants received
      the 16-sample set. The repeatability standard deviations (RSDr) for total fat
      ranged from 2.04 to 10.6%; the reproducibility standard deviations (RSDR) for
      total fat ranged from 3.74 to 15.8%. The hydrolytic extraction-GC method for
      determination of fat (total, saturated, and monounsaturated) in foodstuffs has
      been adopted first action by AOAC INTERNATIONAL.

PMID- 9170656
TI  - Gas chromatographic method for putrescine and cadaverine in canned tuna and
      mahimahi and fluorometric method for histamine (minor modification of AOAC
      Official Method 977.13): collaborative study.
AB  - A collaborative study was conducted to test a modification to the AOAC
      fluorometric method for histamine (AOAC Official Method 977.13) that substitutes
      75% methanol as the extracting solvent. All other steps remain unchanged. The
      extracts prepared with 75% methanol were also used to collaboratively test a gas
      chromatographic (GC) method for determination of putrescine and cadaverine in
      seafood. In the GC method, the extracted diamines are converted to fluorinated
      derivatives, the reaction mixtures are passed through solid-phase extraction
      columns, and the derivatives are quantitated by electron capture GC after
      separation on an OV-225 column. Fourteen laboratories using the GC method for
      putrescine and cadaverine and 16 laboratories using the fluorometric method for
      histamine analyzed 14 canned tuna and raw mahimahi (including blind duplicates
      and a spike) containing 0.2-2.6 ppm putrescine, 0.6-9.1 ppm cadaverine, and 0.6
      154 ppm histamine. At the 5 ppm level, recoveries ranged from 71 to 102% for
      putrescine and 77 to 112% for cadaverine; the respective repeatability relative
      standard deviations (RSDr) were 5.2 and 15%, and the respective reproducibility
      relative standard deviations (RSDR) were 8.8 and 18%. At the 50 ppm level,
      histamine recoveries ranged from 84 to 125%, RSDr was 3.6%, and RSDR was 9.4%.
      The GC method for determination of putrescine in canned tuna and cadaverine in
      canned tuna and mahimahi has been adopted first action by AOAC INTERNATIONAL, and
      the AOAC Official Method 977.13, Histamine in Seafood, Fluorometric Method, has
      been modified.

PMID- 9170657
TI  - Certification of nutrients in Standard Reference Material 1846: infant formula.
AB  - In 1996, the National Institute of Standards and Technology (NIST) released
      Standard Reference Material 1846 (Infant Formula), which can be used as a control
      material for assigning values to in-house control materials and for validating
      analytical methods for measurement of proximates, vitamins, and minerals in
      infant formula and similar matrixes. The SRM was manufactured by preparing a
      spray-dried formula base containing fat, protein, carbohydrates, and minerals and
      then combining that formula base with a dry-blend vitamin premix that supplied
      the vitamins. The Certificate of Analysis for SRM 1846 provides assigned values
      for concentrations of proximates (fat, protein, etc.), vitamins, and minerals for
      which product labeling is required by the Infant Formula Act of 1980 and by the
      Nutrition Labeling and Education Act of 1990. These assigned values were based on
      agreement of measurements by NIST and/or collaborating laboratories. Certified
      values are provided for vitamins A (trans), E, C, B2, and B6 and niacin.
      Noncertified values are provided for solids, ash, fat, nitrogen, protein,
      carbohydrate, calories, vitamin D, delta-tocopherol, gamma-tocopherol, vitamin
      B1, vitamin B12, folic acid, pantothenic acid, biotin, choline, inositol,
      calcium, phosphorus, magnesium, iron, zinc, copper, sodium, potassium, and
      chloride. Information values are provided for iodine, manganese, selenium, and
      vitamin K.

PMID- 9170658
TI  - Rapid liquid chromatographic method to distinguish wild salmon from aquacultured
      salmon fed synthetic astaxanthin.
AB  - Analytical methods are needed to determine the presence of color additives in
      fish. We report a liquid chromatographic (LC) method developed to identify the
      synthetic form of the color additive astaxanthin in salmon, based on differences
      in the relative ratios of the configurational isomers of astaxanthin. The
      distributions of configurational isomers of astaxanthin in the flesh of wild
      Atlantic and wild Pacific salmon are similar, but significantly different from
      that in aquacultured salmon. Astaxanthin is extracted from the flesh of salmon,
      passed through a silica gel Sep-Pak cartridge, and analyzed directly by LC on a
      Pirkle covalent L-leucine column. No derivatization of the astaxanthin is
      required-an important advantage of our approach, which is a modification of our
      previously described method. This method can be used to distinguish between
      aquacultured and wild salmon. The method has general applicability and can also
      be used to identify astaxanthins derived from other sources such as Phaffia yeast
      and Haematococcus pluvialis algae.

PMID- 9170659
TI  - Determination and degradation of methomyl in tomatoes and green beans grown in
      greenhouses.
AB  - A liquid chromatographic (LC) method using UV detection at 233 nm was used to
      study the degradation of methomyl in tomatoes and green beans grown in
      greenhouses. A liquid-liquid extraction with CH2Cl2-methanol (90 + 10, v/v) and a
      cleanup step with Florisil were combined with LC to isolate, recover, and
      quantitate the pesticide. Average recoveries obtained at spike levels of 0.03 and
      0.40 mg/kg were 83.2-84.7% for tomatoes and 83.3-87.5% for green beans.
      Determination limits were 0.03 mg/kg for tomatoes and 0.01 mg/kg for green beans.
      Levels of methomyl residues were studied in tomatoes and green beans grown in an
      experimental greenhouse to establish the effect of the kind of greenhouse,
      application dose, species grown, and climatic conditions on the degradation of
      this pesticide. Analysis of variance showed that doses did not affect the
      response. The half-life, however, is greater in a flat-roof greenhouse than in an
      asymmetric-roof greenhouse and is significantly longer for green beans than for
      tomatoes and longer in winter than in spring. A preharvest time of about 5 days
      may be suitable for green beans sprayed with methomyl. Tomatoes show residue
      levels at the time of application lower than Spanish minimum residue levels.

PMID- 9170660
TI  - Extraction and cleanup of organochlorine and organophosphorus pesticide residues
      in fats by supercritical fluid techniques.
AB  - A supercritical fluid extraction and cleanup procedure was developed for
      separating organochlorine and organophosphorus pesticides from fats.
      Supercritical carbon dioxide modified with 3% (v/v) acetonitrile was used to
      extract the pesticides at 60 degrees C and separate the pesticides from the fats
      at 4000 psi and 95 degrees C on an in-line, C1 silica-based column. The
      extraction and cleanup procedure gave good recoveries for 43 of 62 nonpolar to
      moderately polar organochlorine and organophosphorus pesticides from fats,
      whereas 49 were recovered through conventional Florisil column cleanup before
      quantitation. This procedure can extract and clean up pesticide residues from
      0.65 g animal-based fat and 1.0 g oils. Coeluted residues in the pesticide
      fraction ranged from 2.5 mg for butterfat to 0.8 mg for corn oil. Results for
      samples analyzed with this integrated extraction cleanup procedure were
      reproducible and comparable with results obtained with the current Total Diet
      Study methodology.

PMID- 9170661
TI  - Determination of o-phenylphenol, diphenylamine, and propargite pesticide residues
      in selected fruits and vegetables by gas chromatography/mass spectrometry.
AB  - A simple and rapid method was developed to detect o-phenylphenol, diphenylamine,
      and propargite in selected fruits and vegetables. Gas chromatography/mass
      spectrometry in the selective-ion monitoring mode was used to identify and
      quantitate the 3 residues. Residues were extracted with acetonitrile and
      transferred to acetone. Limits of detection were 10, 8, and 15 ppb for o
      phenylphenol, diphenylamine, and propargite, respectively. Recovery data were
      obtained by fortifying 4 matrixes (apples, oranges, canned peaches, and spinach)
      at 0.025-0.888 ppm. The method provides very good linearity data with low
      coefficients of variation.

PMID- 9170662
TI  - Improved protocol for an oxygen electrode method for determining hydrogen
      peroxide in foods.
AB  - An oxygen electrode method for determining residual hydrogen peroxide in foods
      has been further improved. Pretreatment, which includes extraction and
      neutralization, is done in a hydrogen peroxide extraction apparatus with nitrogen
      gas bubbling. The hydrogen peroxide concentration of the sample is corrected by
      subtracting the sample blank value, obtained for the sample through catalase
      treatment. Bubbling with nitrogen gas effectively minimized the sample blank
      value, making this method suitable for accurate determination of trace amounts of
      hydrogen peroxide in foods. Recoveries of hydrogen peroxide added at 1-10
      micrograms/g were 77.8-107.1% by the present method. These recoveries are similar
      to or higher than those by the Japanese standard method and by another modified
      oxygen electrode method. Concentrations of naturally occurring hydrogen peroxide
      in solid foods were < 0.87 microgram/g by the present method, lower than those by
      either the standard method or another modified oxygen electrode method.

PMID- 9170663
TI  - Preparation of some toxic metabolites of disulfoton, phorate, and terbufos, their
      separation by thin-layer chromatography and confirmation by electron impact mass
      spectrometry.
AB  - Milligram quantities of sulfoxides, sulfones, and oxygen analogue (oxon) sulfones
      of the insecticides disulfoton, phorate, and terbufos were prepared by selective
      oxidation. Pure insecticides or acetone extracts of granular formulations served
      as reactants. Structures of 9 compounds were confirmed by comparing their
      electron impact mass spectra (EI-MS), obtained by the direct inlet system with
      published data. Thin-layer chromatography (TLC) on silica gel was used to screen
      oxidation products and to purify products. Products were detected by spraying
      plates with PdCl2 reagent and exposing to iodine vapors. An esterase inhibition
      technique gave low detection limits, which are promising for residue analysis.

PMID- 9170664
TI  - Diet and cancer.

PMID- 9170665
TI  - Chronic illness peer support.

PMID- 9170666
TI  - Cancer screening in general practice.
AB  - Screening for cancer is the focus of increasing interest and activity in general
      practice. Where clear evidence and guidelines are available, the GP has a key
      role in the promotion of screening. Where the evidence is inconclusive, GPs are
      faced with the more difficult task of negotiating screening decisions with their
      patients which reflect this uncertainty and incorporate patients' preferences.
      GPs play a central role in cancer screening in Australia, whether or not they
      actually provide the tests. Critical activities include the provision of
      information and coordination of the screening process. On-going education and
      skill development in this area is, therefore, a high priority for Australian GPs.

PMID- 9170667
TI  - 'Do I have a brain tumour, doctor'?
AB  - Brain tumours cause symptoms through raised intracranial pressure, epilepsy and
      local effects. The progressive worsening of these symptoms and signs is the most
      important clue to the presence of a tumour.

PMID- 9170668
TI  - Cancer in children.
AB  - Cancer is an uncommon disease in children. The majority of children who develop a
      malignancy are under the age of 5 years with the commonest tumours being those of
      the bone marrow, lymphoid systems and central nervous system. Solid tumours in
      children are almost always sarcomas. Tumours of epithelial origin (or carcinomas)
      are exceedingly rare. The cause of the various paediatric cancers is largely
      unknown, and preventive measures are therefore unavailable to combat them.
      Despite this, there have been significant gains made in the past 20 years, such
      that 60% of all children who present with a malignancy in the 1990s can expect to
      be cured.

PMID- 9170669
TI  - Cancer in the family. Guidelines for general practice.
AB  - In the past 2 years the major genes for inherited breast-ovarian cancer, bowel
      cancer and melanoma have been identified. Relatives of cancer patients frequently
      perceive themselves to be at high risk of cancer. Appropriate assessment of the
      family history permits the identification of those at particularly high risk who
      may benefit from special programs of prevention, screening and surveillance. In
      certain cases, genetic testing and prophylactic surgery may be indicated. This
      article looks at the general issues involved. A follow-up article next month will
      look at specific diseases.

PMID- 9170670
TI  - When to say stop.
AB  - The decision to say stop is unequivocally one for the patient alone. The general
      practitioner's role is to ensure that the patient understands the problem as
      fully as possible and appreciates the various treatment options and all their
      ramifications.

PMID- 9170671
TI  - Myths, misconceptions and the autopsy.
AB  - Although examination of the dead to determine why a death occurred has probably
      been undertaken from the earliest times, formal investigation by a qualified
      specialist medical practitioner is a much more recent phenomenon. Unfortunately a
      number of misapprehensions and myths concerning the role and process of autopsy
      examination exist. While autopsies are not all that common, most medical
      practitioners have been faced with the onerous task of explaining to relatives
      what happens to the body during and after an autopsy. The following paper deals
      with some of the concerns that are periodically raised by non pathologist
      physicians and health care workers who are involved with grieving relatives. The
      text is aimed at health care workers and is not in an appropriate format for
      relatives.

PMID- 9170672
TI  - Prader-Willi syndrome.
AB  - People with Prader-Willi syndrome (PWS) and their families provide a unique
      challenge to the general practitioner. This article provides an outline of the
      key information and management issues for general practitioners who care for
      people with PWS and their families.

PMID- 9170673
TI  - Hospital based primary care clinics. Complementary to general practice.
AB  - OBJECTIVE: To describe the patients attending a hospital based primary care
      clinic (HBPCC) focusing on the main medical and non-medical reasons for their
      seeking health care at the clinic, and their expectations of, and satisfaction
      with the care. METHODS: The study was set in a HBPCC in the northern region of
      metropolitan Melbourne, Australia. Bilingual interviewers assisted consecutive
      new patients to complete a pre- and post-consultation questionnaire seeking
      information on the presenting complaint, patient-reported reason for encounter
      (RFE), doctor-recorded health problem, treatments received, and patient
      expectations of and satisfaction with care. RESULTS: The sample (n = 197) was
      young (mean age 33 years). A high proportion came from a low socioeconomic group
      (68%) and there was a higher than expected proportion of patients with a non
      English speaking background (NESB) (53%). Three-quarters had a regular GP
      elsewhere. Important reasons for choosing this service were accessibility and
      familiarity: being part of a hospital: case of obtaining radiological
      examinations, and the quality of the doctors. The commonest health problem was
      trauma related (14-16%). The main body systems involved were locomotor, skin,
      digestive, respiratory, pregnancy related and non specific. Patients were mostly
      satisfied with their cares those with ill-defined problems were more likely to
      report that their expectation were not completely met. There were no significant
      demographic and ethnic variations in the outcome variables. CONCLUSION: HBPCCs
      can complement the GP's ongoing relationship with patients from NESB and lower
      socioeconomic groups to improve the continuity and coordination of healthcare.
      Experienced and culturally sensitive GPs, good communications, and an effective
      and comprehensive interpreter service are necessary to facilitate this care
      coordination. One strategy is a hospital based department of general practice
      linking academic GPs and a local divisional network of GPs, to provide this
      clinical service and undertake teaching and research in the areas highlighted by
      this study.

PMID- 9170674
TI  - Effective breastfeeding support in a general practice.
AB  - OBJECTIVE: To determine the effectiveness of a breastfeeding support service
      attached to a general practice. DESIGN: A lactation consultant (LC) was employed
      in a general practice in Happy Valley. Adelaide over 12 months to provide an
      appropriate intervention program of education and support for mothers
      experiencing problems with breastfeeding. The mothers were asked to evaluate the
      service via a postal questionnaire. The baseline rates of women in this practice
      who were solely breastfeeding were determined by a retrospective questionnaire
      sent to all mothers of the practice whose children were 18 months to 2 1/2 years
      of age (168 mothers formed this baseline group). There were 119 mothers in the
      intervention group. RESULTS: There was a high, breastfeeding initiation rate for
      both baseline (94.6%) and intervention (93.4%) groups. There were significantly
      higher breastfeeding rates in the intervention group at 24 and 26 weeks (63.3% vs
      51.2% at 24 weeks [p = 0.015] and 64.7% vs 50.6% at 26 weeks [p = 0.018]). While
      there was no significant difference in the total number of breastfeeding problems
      encountered by either group significantly more mothers from the baseline group
      suffered from engorgement and/or too much milk. Evaluation of the service
      indicated a high degree of satisfaction. Over 94% of the mothers found the
      service friendly, supportive, and useful. CONCLUSIONS: This service provides an
      effective method for the support and protection of breastfeeding.

PMID- 9170675
TI  - Sports medicine. A specific problem in the groin.

PMID- 9170676
TI  - Anterior knee pain.

PMID- 9170677
TI  - Type 2 diabetes.

PMID- 9170678
TI  - A lump in the neck.

PMID- 9170679
TI  - Bubbles in the water.

PMID- 9170680
TI  - Management of labial adhesions.

PMID- 9170681
TI  - T and Z scores in osteoporosis.

PMID- 9170682
TI  - Just say yes: how are we doing in the war against illegal drug use?

PMID- 9170683
TI  - Incidence of iron-deficiency anaemia and depleted iron stores among nine-month
      old infants in Vancouver, Canada.
AB  - The iron status and feeding practices of 434 infants in Vancouver were determined
      at 39 +/- 1 week of age. Iron-deficiency anaemia (haemoglobin < or = 101 g/L, or
      < or = 110 g/L with two or three abnormal results from tests of serum ferritin,
      zinc erythrocyte protoporphyrin and total iron binding capacity) occurred in 7%
      of infants. Low iron stores (serum ferritin < 10 micrograms/l) occurred in about
      24% of infants. Iron-deficiency anaemia was significantly associated (p < 0.001)
      with duration of breastfeeding. The prevalence of iron-deficiency anaemia among
      infants breastfed for 8 months was 15%. At 39 weeks (9 months) of age, about 5%
      and 13% of the infants were bottle-fed with cows milk or low iron infant formula,
      respectively, and this was also significantly associated (p < 0.02) with low iron
      stores. Iron-fortified infant cereals had been introduced to 95% of the infants
      by six months of age. This study shows iron-deficiency anaemia is a problem among
      a significant number of nine-month-old infants in Canada, and is not explained by
      failure to introduce iron-fortified infant cereals.

PMID- 9170684
TI  - How a print resource on policy change was used by community and public health
      practitioners.

PMID- 9170685
TI  - A population-based hepatitis B seroprevalence and risk factor study in a northern
      Ontario town.
AB  - OBJECTIVE: To determine a) population-based hepatitis B seroprevalence rates; and
      b) associated behavioural risk factors. SETTING: A remote northern Ontario town
      with a cluster of hepatitis B cases. INTERVENTIONS: Anonymous blood testing
      linked with risk-factor questionnaires. RESULTS: 635 persons aged 14 to 30 years
      (51% of the eligible age cohort) donated blood in return for free vaccination;
      four were anti-HBs positive, and none was HBsAg positive. In all, 19% of
      participants reported two or more sexual partners in the previous year, 6%
      reported at least one tattooing in the previous year, and 1% reported illicit
      injection drug use. Of persons with multiple sexual partners 84% did not
      consistently use condoms. CONCLUSIONS: When the serological results of the
      original cluster (and contacts) were considered, the age cohort's HBsAg
      seroprevalence rate was estimated to be between 0.24% and 0.47%. While the
      serosurvey did not discover additional HBsAg positive cases, there was great
      potential for heterosexual transmission.

PMID- 9170686
TI  - Hepatitis C in Prince Edward Island: a descriptive review of reported cases, 1990
      1995.
AB  - INTRODUCTION: The prevalence of hepatitis C in Canada is not known. There is
      limited information on most small area populations such as Prince Edward Island.
      METHODS: A retrospective approach was used to obtain detailed information on all
      cases of hepatitis C identified in Prince Edward Island from December 1990 to
      September 1995. Cases were reviewed for demographic, clinical and risk factor
      information, including blood donation and transfusion histories. RESULTS: There
      were 54 RIBA confirmed cases of hepatitis C infection included in the Prince
      Edward Island Hepatitis C Database, of which 38 (70%) were males. Age ranged from
      18 to 76 years, with a mean age of 38 years. Twenty-eight (52%) of the cases had
      a history of injection drug use, and 24 (44%) had received blood or blood
      products in the past. There were five cases with neither of these risk factors
      identified. DISCUSSION: The results suggest that, in this small, primarily rural
      population, injection drug use is the most common means of hepatitis C
      transmission, followed by receipt of blood or blood products.

PMID- 9170687
TI  - Facilitating the shift to population-based public health programs: innovation
      through the use of framework and logic model tools.
AB  - Program planning and evaluation are critical steps in using a population health
      approach. This paper outlines how logic models have been adapted within a health
      promotion framework to guide public health programs and facilitate program
      description. It is important that we take the time to describe clearly what we
      are doing, reflect on practice and elaborate the conceptual base for the new
      public health programs so that we can evaluate the impact of our work. Ongoing
      research is required to identify appropriate and measurable indicators that
      capture the process, as well as the outcome, of population-based health
      promotion.

PMID- 9170688
TI  - Kidney cancer in Canada: the rapidly increasing incidence of adenocarcinoma in
      adults and seniors.
AB  - PURPOSE: To examine kidney cancer incidence and mortality patterns since 1969 in
      Canada. METHOD: Linear regression of the log rates was used to estimate secular
      trends by age group and sex, and age-period-cohort models were fitted to examine
      changes in kidney cancer and renal adenocarcinoma incidence rates. RESULTS: A
      substantial increase in incidence rates was observed among those 35 years and
      older, with average increases of 2.5% or more annually for both sexes. Age-period
      cohort modelling suggested that much of this increase resulted from a period
      effect. Changes in mortality were much more modest, especially among those aged 0
      34, for whom mortality rates actually declined by an average of 4.2% and 5.4%
      annually for males and females respectively. CONCLUSIONS: Kidney cancer incidence
      rates have increased significantly, especially renal adenocarcinoma among adults
      and seniors. Diagnostic improvements and increasing levels of obesity in the
      Canadian population may have contributed to these trends.

PMID- 9170689
TI  - The contemporary food supply of three northern Manitoba Cree communities.
AB  - A complex set of social, economic, cultural and environmental circumstances
      affecting native Canadians in northern regions has resulted in the dietary
      replacement of indigenous foods with marketed products not always of equivalent
      nutritional value. This article examines the current food supply in three
      northern Manitoba Cree communities by looking at the availability and
      preservation of traditional foods, the price of marketed foods and perceptions of
      the food supply. Data were obtained by questionnaire from older adults (over 55
      years) and younger women (16-45 years) in each community. The food supply
      comprised a mix of traditional and marketed foods, with limited use of
      traditional methods of food preservation. Marketed food prices were high in
      communities without all-weather road access. Respondents expressed a desire for
      more traditional food. Promotion of traditional foods could increase nutrient
      intake, decrease food costs and contribute to a revival of interest in Cree
      culture.

PMID- 9170690
TI  - Introduction of high-alcohol beer in Ontario: preliminary observations on its use
      by underage drinkers.
AB  - Preliminary data are reported on the use of high-alcohol beer by underage
      drinkers in Ontario. Students in grades 11 and 12 with a valid driver's licence
      completed a questionnaire between January and May, 1994 (i.e., between three and
      seven months after the introduction of high-alcohol beer). About one-half of
      students who had drunk alcohol within the previous four weeks reported consuming
      high-alcohol beer within that period. In this group, males were much more likely
      to report high-alcohol beer consumption in the previous month. Both male and
      female high-alcohol beer consumers drank alcohol more frequently, got drunk more
      frequently, and drank five or more drinks on the same occasion more frequently
      than non-consumers. One reason for trying high-alcohol beer, "wanted a higher
      alcohol content", was endorsed by more than one-third of high-alcohol beer
      consumers. Our data suggest that the users of high-alcohol beer among this
      underage drinking sample tend to be heavier drinkers and more likely to
      experience alcohol-related problems.

PMID- 9170691
TI  - Ultraviolet radiation and safety behaviours at an outdoor community event.
AB  - The incidence of skin cancer is rising drastically and is believed to be at
      epidemic proportions. Although preventive efforts have focused mainly on
      increasing public knowledge of the dangers associated with ultraviolet radiation,
      increased knowledge does not consistently translate into safe sun practices. The
      present study provided a "snapshot" of knowledge, attitudes and actual behaviour
      related to sun safety in a sample of 2,064 individuals attending a major
      community event. Despite almost uniform acknowledgement of a sun-cancer link, and
      the belief that certain behaviours can reduce the chances of getting skin cancer,
      only 38% of respondents reported wearing sun screen. Differences in sun safe
      behaviours were observed across age groups. The present results emphasize the
      need to target behaviours as well as knowledge and attitudes regarding sun
      safety.

PMID- 9170692
TI  - A randomized controlled trial of alternative approaches to community follow-up
      for postpartum women.
AB  - This three-group randomized controlled trial assessed the effectiveness of a
      postpartum public health nurse telephone visit on infant-care behaviours of
      primiparous women in Ottawa-Carleton. The impact of a clerk call on recruiting
      mothers to parent-baby groups was also described. Low risk primiparas were
      randomized into telephone visit, clerk call and control groups. At three months
      postpartum, there were no significant differences in infant-care behaviour scores
      among the study groups. Women who received the telephone visit had the highest
      parent-baby group attendance rates and among attenders, the highest rates of
      smoking during pregnancy, the least education, and lowest incomes. Analysis of
      variance revealed a significant interaction term between attendance at parent
      baby groups and assigned study group. This effect disappeared after adjusting for
      age and education. The telephone visit was no more effective in producing the
      desired infant-care behaviour changes than a mailed out information package with
      or without a clerk phone call. However, the intervention did increase the
      utilization of parent-baby support groups by women who were more
      socioeconomically disadvantaged.

PMID- 9170693
TI  - The STEPS Project: participatory action research to reduce falls in public places
      among seniors and persons with disabilities.
AB  - Through a process of participatory action research involving a telephone hotline,
      the STEPS project compiled data over a nine month period on the location and
      nature of 791 pedestrian slips, trips, falls and potential hazards in the Capital
      Regional District of British Columbia. Of the 533 people who reported a slip,
      trip or fall, the majority (80%) were female, and the average age was 65.27
      years. Thirty-five percent (n = 186) had some type of physical disability and
      many (n = 106) reported using a mobility aide at the time of their accident. Most
      callers (75%) said they had suffered an injury, and of these 55% required medical
      attention. The most frequently reported fall locations were sidewalks and
      crosswalks. Major recommendations from the study include the need for municipal
      priority-setting for repairs with input from key user groups, including the
      elderly and people with disabilities.

PMID- 9170694
TI  - Female genital mutilation.

PMID- 9170695
TI  - Emerging and re-emerging communicable diseases.

PMID- 9170696
TI  - Creutzfeldt-Jakob disease and growth hormone therapy.

PMID- 9170697
TI  - Evaluating asthma.

PMID- 9170698
TI  - An appeal to the Canadian international health community.

PMID- 9170699
TI  - The validity of qualitative research.

PMID- 9170700
TI  - Emergence of further serotypes of multiple drug-resistant Streptococcus
      pneumoniae in Queensland.
AB  - We describe 27 cases of multiple drug-resistant pneumococcal infection in
      Queensland children (7 cases) and adults (20 cases), between February 1995 and
      October 1996. Seven patients had invasive disease. Serotypes were those commonly
      associated with paediatric infections and included types 19F (15 strains), 14
      (6), 23F (4), 6A (1) and 19A (1). No rifampicin or vancomycin resistance was
      encountered. However, pneumococci fully resistant to cotrimoxazole, erythromycin
      and tetracycline were isolated from 25 of 27 cases (93%). Strains with high level
      resistance to penicillin and chloramphenicol were also recovered from 16 (59%)
      and 19 (70%) patients respectively. Twelve of 16 penicillin-resistant isolates
      showed intermediate resistance to ceftriaxone and two strains were fully
      resistant to this antibiotic. Clones of types 19F and 14 pneumococci, each with
      two distinctive resistance patterns, appear to be established in south-east
      Queensland.

PMID- 9170701
TI  - Communicable diseases surveillance. Legionellosis.

PMID- 9170702
TI  - Renal pelvic tumor in a horseshoe kidney.

PMID- 9170703
TI  - Posterior tibial tendon dysfunction as a cause of acquired flatfoot in adults.

PMID- 9170704
TI  - Disabilities.

PMID- 9170705
TI  - School health talks and doctor/lawyer talks update 1997.

PMID- 9170706
TI  - The physician's duty to report a patient to motor vehicle authorities: when must
      you report and what are your liabilities.

PMID- 9170707
TI  - Medical savings account: available at last.

PMID- 9170708
TI  - Atelectasis and chronic suppurative otitis media.

PMID- 9170709
TI  - Multiple recurrent laryngeal granulomas.

PMID- 9170710
TI  - The Caldwell-Luc procedure--is it still indicated in this endoscopic sinus
      surgery era?

PMID- 9170712
TI  - Recent developments in air-conduction hearing aids.
AB  - From a history of hearing aids based on analog signal processing, the door has
      just opened to a new "room," the digital hearing aid room. Previously, the more
      complex signal processing schemes could be tested only at the lab and rarely in
      real-life environments. The advent of wearable digital hearing aids primarily
      means that we have much more powerful tools available now, allowing us to test
      various ideas for signal processing in true field tests over sufficient
      durations. Since the different processing schemes will be controlled by software
      (the program or algorithm that has been stored in the hearing aid), we will be
      able to design truly blind field tests for the comparison of different
      processing, thereby avoiding the bias for the new aid versus the old aid which
      has always plagued clinical trials of hearing aids thus far. It is not very
      likely that the digital era in hearing aids will solve all problems in a short
      time. I am convinced that we have just started on a slow process into this
      "digital room." What, precisely, we will find there of value is hard to tell, but
      I am equally convinced that the main effects will be of noticeable benefit to the
      user. It is also very likely that some of the lessons we will learn in our future
      digital experiments will be useful not only for air-conduction hearing aids, but
      also for other types of technical aids for the hearing-impaired and the deaf.

PMID- 9170711
TI  - Implantable hearing device performance measured by laser Doppler interferometry.
AB  - Recent application of the Doppler principle laser interferometry to audiology,
      acoustics and otology has facilitated the development of implantable hearing
      devices (IHDs). During the design and testing of two different electromagnetic
      middle ear implants for sensorineural hearing loss, we used single-point laser
      Doppler interferometry (LDI). A commercially available interferometer, internally
      calibrated and validated against a National Institute for Standards and
      Technology (NIST) standard, was used with both mechanical fixtures and fresh
      temporal bones to evaluate implant mass, shape and orientation, attachment,
      electromagnetic coupling and acoustic properties. At both Hough Ear Institute and
      Symphonix Devices, Inc., we have shown that high fidelity and amplitudes can be
      recorded in vitro over a frequency range of 500 Hz to 10 kHz. These data can
      provide greater assurance of safety and efficacy to regulatory agencies before
      entering clinical trials. We propose that LDI be considered as an international
      standard for accurate, consistent comparison of performances of all IHDs during
      development. Furthermore, the future availability of human IHD data will allow
      for the extrapolation of a mechanical bench model of the middle ear transfer
      function for use in quality control during manufacturing and diagnosis of failure
      in IHDs.

PMID- 9170713
TI  - Masking the protrusion of the receiver-stimulator of electronic implants in
      otology.
AB  - Protrusion of the receiver-stimulator of a cochlear implant or a piezoelectric
      implantable hearing aid (IHA) was masked using bone dust applied in the gap
      between the receiver and the surrounding bone, making a smooth transitional
      border. The bone dust was then fixed with fibrin glue. Bone pate (a mixture of
      bone dust and fibrin glue) was also used to fix the lead wire of a cochlear
      implant at the region of the posterior tympanotomy and to fasten an IHA vibrator
      holder to the temporal bone. Over the past two years, the use of these techniques
      in six patients with cochlear implants and two patients with IHAs has resulted in
      gratifying results; the edge of the receiver remained flush in all cases. They
      have been free from problems such as infection of the wound, necrosis of the
      overlying skin, and protrusion or migration of the receiver.

PMID- 9170714
TI  - Mechanical, acoustic and electromagnetic evaluation of the semi-implantable
      middle ear hearing device (SIMEHD).
AB  - The properties of the partially implantable middle ear hearing device (SIMEHD)
      were extensively studied. The internal unit was subjected to 5,000 cycles of
      bending at a force of 75 g (gravity) without failure. An accurate measurement of
      the force output of the SIMEHD was obtained (14-25 dynes/mA). This force is too
      small to cause any damage to the ossicular chain. The force resulting from
      electromagnetic interference over a wide frequency range (500 khz -1 Giga (10(9))
      Hz) was measured and noted to be within the margin of safety. The frequency
      response plots (500-8,000 Hz) were also obtained and revealed an excellent
      ability to amplify middle and high-frequency sounds.

PMID- 9170715
TI  - A bone-anchored percutaneous connector system for neural prosthetic applications.
AB  - A percutaneous connector system has been developed for use in neural prosthetic
      applications. It is based on a skin-penetrating, bone-anchored titanium pedestal,
      housing an II-channel electrode array. Initial applications for the system are in
      audiology and as such, the proposed fixture site is in the temporal bone. The
      titanium pedestal is based on existing design features of the EPI Bioglass
      implant, developed by University College London (UCL), and the Branemark System,
      employed by Nobel Biocare AB. The electrode array, consisting of platinum wires
      in a silicone carrier, can be custom designed to suit the application. The design
      features of the connector system are reviewed. Animal studies have been used to
      assess soft tissue reactions and the osseointegration of the pedestal. The
      histological data are presented. The pedestal, electrode array and the mating
      external connector are currently undergoing mechanical and electrical testing.
      The percutaneous connector system will undergo clinical trials, initially in the
      study of tinnitus (employing stimulation via an extracochlear electrode), and as
      part of a cochlear implant system (using a multichannel intracochlear electrode
      array and digital signal processing techniques.

PMID- 9170716
TI  - Semi-implantable middle ear electromagnetic hearing device for sensorineural
      hearing loss.
AB  - A semi-implantable middle ear electromagnetic hearing device (SIMEHD) is proposed
      for limited clinical trial in adult patients to evaluate the implantable hearing
      device for moderate to severe sensorineural hearing loss. Food and Drug
      Administration (FDA) investigational device exemption (IDE) approval has been
      granted (May 1996) for clinical trials. The implant unit has been evaluated
      acutely and chronically in animals (cats) with excellent results. Five cats
      undergoing chronic implantation were allowed to survive an average of 9.6 months,
      showing that the SIMEHD is biocompatible, functional and without untoward
      complications. All implant units recovered from the cats were functional, except
      for wire breakage of the internal antenna. A new antenna was redesigned for human
      implantation. The SIMEHD system consists of an external and internal unit. The
      external unit consists of a microphone, audio amplifier, modulator, radio
      frequency (RF) amplifier, antenna and battery. The internal unit is composed of a
      receiving antenna, hybrid electronic circuit, air core driving coil, and a target
      magnet cemented to the incus. All materials in contact with the body are
      biocompatible and expected to survive indefinitely. The implant unit is
      miniaturized and manufactured with existing fabrication technology by our
      industrial collaborator, Wilson Greatbatch, Ltd. The specific aims and major
      tasks of the proposed research are: a) to evaluate reliability, safety and
      efficacy of the SIMEHD system in a selected group of patients diagnosed with
      sensorineural hearing loss, due mainly to presbycusis or aging of the inner ear;
      and b) to obtain objective and subjective evaluation of audiologic and
      psychoacoustic performance as compared to the acoustic hearing aid. This paper
      describes the design, illustrates the actual device (newest prototype) and
      details the technique for surgical implantation in the attic and mastoid antrum
      in humans.

PMID- 9170718
TI  - Efficacy of fluoride against dental caries; fluoride in water.

PMID- 9170717
TI  - Papillary carcinoma of the thyroid metastatic to the parapharyngeal space.
AB  - The parapharyngeal space is a complex anatomic area which can give rise to a
      variety of both primary and metastatic neoplasms. Squamous cell carcinoma can
      also present as a parapharyngeal space mass, either by direct extension or by
      metastases. Occult thyroid carcinoma presenting as a parapharyngeal space mass is
      a rare clinical occurrence which has been only sporadically reported in the
      medical literature. We present a case of occult papillary thyroid cancer with
      parapharyngeal space metastasis in the form of an isolated tumor, as well as a
      review of the literature on similar presentations. This rare situation has been
      previously described only once in the medical literature. Metastatic thyroid
      cancer should be considered in the differential diagnosis of a parapharyngeal
      space mass.

PMID- 9170719
TI  - Systemic fluorides apart from fluoride in water.

PMID- 9170720
TI  - Topical fluorides (especially toothpaste).

PMID- 9170721
TI  - The role of diet in dental caries.

PMID- 9170722
TI  - Cariogenicity tests.

PMID- 9170723
TI  - Oral cancer and precancerous lesions.

PMID- 9170724
TI  - Oral health as a public health indicator.

PMID- 9170725
TI  - Microbiology of caries and periodontal diseases.

PMID- 9170726
TI  - The effect of a new oral hygiene training program on approximal caries in 12-15
      year-old Brazilian children. Results after three years.

PMID- 9170727
TI  - A double blind clinical study on the effectiveness of a chlorhexidine containing
      lozenge (Septofort) in the treatment of chronic gingivitis.

PMID- 9170728
TI  - Welfare to work: analysis and recommendations.

PMID- 9170729
TI  - Introduction to the AFDC program. Aid to Families with Dependent Children.
AB  - This journal issue discusses the policy challenges of helping parents move from
      welfare to work. As a foundation, this introductory article explains the federal
      state program of cash assistance called Aid to Families with Dependent Children
      (AFDC), to which the term welfare refers in most of these articles. While a
      number of other social programs are sometimes included under the umbrella of
      welfare-such as the Supplemental Security Income program for the disabled, food
      stamps, and Medicaid-the program that has drawn the most public scrutiny and
      negative attention, and the centerpiece of the 1996 welfare reform legislation,
      is AFDC. This article explains the basic structure of the AFDC program, including
      eligibility criteria and benefits; discusses the characteristics of families that
      have received AFDC; describes trends in the program's size and cost from the
      1970s to 1996; and indicates the major ways in which the block grant established
      in the 1996 welfare reform legislation compares to the AFDC program that it
      replaced.

PMID- 9170730
TI  - A brief history of work expectations for welfare mothers.
AB  - The best known of the nation's welfare programs, Aid to Families with Dependent
      Children (AFDC), has from its inception reflected a tension between the desire to
      support children in poor, lone-parent families and the belief that parents should
      be held responsible for providing for themselves and their children. Against that
      backdrop, this article reviews the history of the AFDC program and traces the
      emergence of policies and programs intended to encourage employment of the
      parents (almost exclusively mothers) who receive benefits. The article examines
      in detail the Work Incentive Program (WIN) launched in 1967 and the Family
      Support Act of 1988, comparing these to each other and to the outlines of welfare
      reform signed into law in 1996. The article emphasizes the importance of
      sustained attention to the implementation of policy goals in concrete programs
      and shows that the merits of those early programs have not been fully tested
      because they were never funded or implemented at the scale intended. The article
      also outlines ways in which welfare-to-work programs can be used to assist
      children as well as parents, and urges that children's well-being remain the core
      purpose of welfare policy.

PMID- 9170731
TI  - Welfare recipients' job skills and employment prospects.
AB  - The welfare reform goal of moving mothers who rely on welfare into private-sector
      employment cannot be achieved only by changes in public policy. Employment rates
      reflect the job qualifications of individuals, obstacles to work outside the
      home, the attractiveness of available jobs, and the capacity of the labor market
      to absorb new workers at particular skill levels. This article examines how each
      of these factors is likely to influence current welfare recipients' success in
      finding employment and the wages they are likely to earn. The author concludes
      that the skill deficiencies of recipients of Aid to Families with Dependent
      Children do not represent an insurmountable barrier to employment, although these
      deficiencies do restrict the wages recipients can earn. Without continued public
      assistance in the form of wage subsidies, child care payments, or help securing
      health insurance, most families that move from welfare to work will remain below
      the poverty level.

PMID- 9170732
TI  - Alternative strategies for increasing employment.
AB  - As states reform their welfare systems to emphasize work and self-sufficiency,
      they can draw on significant past experience with efforts to promote employment.
      Work and training programs for welfare recipients and other disadvantaged
      individuals have been operating in every state for nearly 30 years. This article
      summarizes findings from key evaluations of strategies to increase the employment
      and earnings of individuals. The article also reviews lessons about program
      design and management drawn from studies of program outcomes and implementation.
      Evaluations of net impact typically measure outcomes for randomly selected
      individuals who participated in programs, and compare those with outcomes for
      individuals who did not receive the treatment. Studies of program outcome and
      implementation analyze the effectiveness of entire programs in real-world
      operational settings. The evidence from net-impact evaluations shows that
      programs that encourage, help, or require welfare recipients to find jobs or
      participate in training or work-related activities can increase employment and
      earnings and in some cases reduce welfare costs. Even the most successful
      programs, however, yield only small gains in earnings that do not move most
      former welfare recipients out of poverty. The article also discusses critical
      policy and implementation issues that influence the effectiveness of welfare-to
      work programs overall. It focuses on strategies for increasing rates of
      participation in the programs, for improving implementation, and for
      strengthening links with the local labor market, which ultimately determines the
      success or failure of any welfare-to-work program.

PMID- 9170734
TI  - Turning job finders into job keepers.
AB  - Most welfare-to-work programs designed to help single mothers leave welfare for
      employment focus on the challenge of finding a job. This article looks beyond the
      point of employment to consider the difficulty many former welfare recipients
      have keeping their jobs. The authors review evidence showing that many families
      cycle back and forth between welfare and work, losing jobs and returning to
      public assistance while they seek work again. Factors contributing to high rates
      of job loss include characteristics of the job and of the worker. Temporary jobs,
      frequent layoffs, low pay in relation to work expenses, lack of experience
      meeting employer expectations, and personal or family problems all lead to
      dismissals and resignations. Drawing from the experience of innovative programs,
      the authors recommend policy changes and program approaches that can help
      families overcome setbacks and stabilize their lives as they move from welfare
      into increasingly stable employment.

PMID- 9170733
TI  - The partners of welfare mothers: potential earnings and child support.
AB  - Public interest in promoting the self-sufficiency of families that depend on
      welfare concerns the ability of fathers, as well as mothers, to support their
      children through employment. Many welfare recipients are never-married women, and
      their children seldom receive child support payments. This article estimates the
      financial resources that go untapped when child support is not collected from the
      men who father children who later receive AFDC benefits. While these men may earn
      little at the time the child is born, their incomes are likely to escalate over
      time. The child support payments they would make over the child's first 18 years
      equal almost half of the welfare benefit received by the mother and child. Based
      on these probable long-term earnings, the authors urge policymakers to invest in
      efforts to establish paternity and collect child support.

PMID- 9170735
TI  - Health care coverage for children who are on and off welfare.
AB  - Access to adequate health insurance is a key concern of families with children at
      all income levels. Since 1965, mothers and children on welfare have had health
      care coverage through the Medicaid program, which has provided a health care
      safety net for welfare recipients. Although most Americans are insured through
      their employers, families who leave welfare for employment often find themselves
      in jobs that do not offer health care coverage, adding to the ranks of the
      uninsured. This article examines the extent to which poor children and their
      mothers have private insurance, Medicaid, or no health insurance at all. It
      documents how recent expansions of Medicaid eligibility to low-income children
      who do not receive welfare have improved the insurance status of children, though
      these changes have not helped the mothers who leave welfare for work. Citing
      evidence that health insurance options influence the welfare and employment
      decisions of women whose families face health problems, the article suggests that
      implementing welfare reform at a time when rates of private insurance coverage
      are declining will be challenging and may expose some families to health risks.

PMID- 9170736
TI  - Arranging child care.
AB  - More than half of the children in families supported by welfare are under age
      six, and another third are in grade school. The mothers of these children cannot
      leave welfare for employment unless they can find and pay for child care. Yet, as
      this article points out, the child care needs of these families are not easily
      met: Many require care for infants and toddlers, care at odd hours, and care in
      poor neighborhoods-all of which are scarce. Evidence reviewed by the authors
      indicates that problems with child care affordability, availability, and quality
      impede mothers from participating in the labor force and in job training
      programs. Recent public finding for child care subsidies has helped families
      leaving welfare to afford the child care they need, although the demand for
      financial assistance outstrips available funding. This article urges that
      policymakers work to facilitate access to subsidies, increase the supply of care
      that can meet the needs of poor working families, and guard against exposure to
      poor-quality care that can jeopardize both children's well-being and parents'
      employment.

PMID- 9170737
TI  - When low-income mothers go to work: implications for children.
AB  - When mothers who have depended on welfare become employed, the change affects not
      only welfare budgets and the women themselves, but the daily lives of the
      children who make up two-thirds of the welfare population. This article is the
      first of a set of three that consider what we know--and do not know--about the
      likely effects that a mother's moving from welfare to work will have on her
      children. This article gives an overview of research studies conducted from the
      late 1960s to the present that consider how maternal employment affects children
      in low-income families. The efforts of these families to juggle working and child
      rearing have received far less attention than those of middle-class or
      professional families. Most studies that do focus on low-income groups indicate
      that children are seldom harmed when their mothers work, and many have improved
      outcomes, especially in terms of cognitive development. The authors caution,
      however, that all the working mothers studied thus far entered employment
      voluntarily, so their experiences may be more favorable than the experiences of
      families who may be forced off welfare and into jobs. Child outcome research that
      focuses directly on the families who will be affected by welfare reform is
      currently unavailable. The two subsequent articles (by Parcel and Menaghan and by
      Moore and Driscoll) continue with the themes raised in this overview and examine
      in depth specific questions policymakers should ask as they anticipate the
      effects that moving mothers into low-wage jobs may have on the development of
      children: How does a parent's going to work outside the home affect family life?
      And how do children who were once supported by public assistance fare after their
      mothers become employed?

PMID- 9170738
TI  - Effects of low-wage employment on family well-being.
AB  - Assumptions about the processes that link a mother's employment to the
      development of her child must underlie expectations about how children may fare
      when their mothers move from welfare dependence into employment. This article
      explores the idea, mentioned in the research overview by Zaslow and Emig in this
      journal issue, that the working conditions such as wages, work hours, and task
      complexity that mothers experience on the job can influence their behavior as
      parents and shape the home environments they provide for their children. This
      article discusses the significance of home environments for children's
      intellectual and emotional development and considers how home surroundings change
      when mothers begin jobs that are more rewarding or less rewarding. The authors
      conclude that, while maternal employment is not necessarily harmful, if welfare
      recipients find only low-wage, stressful jobs, working may prove costly for both
      family and child well-being. The authors recommend that welfare-to-work programs
      devote attention to (1) assisting mothers to obtain more complex work at good
      wages, (2) helping mothers understand the role home environments play in shaping
      children's development, and (3) encouraging parents to make their children's home
      surroundings as positive as possible.

PMID- 9170739
TI  - Low-wage maternal employment and outcomes for children: a study.
AB  - Despite the importance of anticipating how children may be affected by policies
      that move mothers off welfare and into employment, as the article by Zaslow and
      Emig in this journal issue points out, few research studies have addressed this
      critical policy question. To help fill that gap, this article presents the
      results of a new study using national survey data to examine child outcomes among
      families that had previously received welfare. About half the families studied
      had mothers who remained at home, the others were working at varying wage levels.
      The findings reported here echo themes discussed in the two preceding articles.
      Maternal employment does not appear to undermine children's social or cognitive
      development from ages 5 to 14, and it may yield advantages. Children whose
      mothers earned more than $5.00 per hour, particularly, had somewhat better
      outcomes than others. The authors emphasize, however, that background
      characteristics specific to the mothers who chose employment contributed to these
      positive outcomes. The authors add that it would be risky to apply these
      generalizations based on these findings to families forced into employment by
      welfare reform.

PMID- 9170740
TI  - Childhood hunger.

PMID- 9170741
TI  - Say no to managed care.

PMID- 9170742
TI  - Shocked.

PMID- 9170743
TI  - Self learning/self assessment.

PMID- 9170744
TI  - CDA is dentistry's voice.

PMID- 9170745
TI  - Amalgam recommendations clarified.

PMID- 9170746
TI  - CDA approves HIV testing guidelines.

PMID- 9170747
TI  - Researchers identify tooth decay antibody.

PMID- 9170749
TI  - What you always wanted to know about PPOs but were afraid to ask.

PMID- 9170748
TI  - U.S. court rules refusal to have children an HIV disability.

PMID- 9170750
TI  - Two independent clinical trials comparing pre-brush mouthrinse formulations in
      reducing supragingival plaque.

PMID- 9170751
TI  - The effects of smoking on periodontal structures: a literature review.
AB  - Periodontal disease seems to be more prevalent in smokers than in nonsmokers.
      Studies have reported both increases and decreases in gingival blood flow due to
      smoking. Smoking does not increase the presence of the periodontopathogens
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Bacteroides
      intermedius. Both the chemotaxis and the phagocytic capacity of the
      polymorphonuclear leukocytes (PMNs) harvested from smokers are lower than with
      those harvested from nonsmokers. Furthermore, smokers have lower IgA, IgG, IgM,
      and suppressor CD8 lymphocytes levels than nonsmokers. These differences between
      smokers and nonsmokers should be taken into account by clinicians during
      periodontal examinations, therapy, and the healing process.

PMID- 9170752
TI  - Treatment outcome of surgical and non-surgical management of endodontic failures.
AB  - The principal modalities available to manage endodontic treatment failures are
      orthograde retreatment and apical surgery. Both modalities have specific
      advantages, clinical implications, and risks, and their selection involves a
      complex decision-making process. A review of the literature pertaining to the
      treatment outcome of each modality was undertaken to establish an objective
      reference for practitioners involved in the management of endodontic treatment
      failures. Based on a weighted average calculation of the results reported in the
      reviewed studies, the orthograde retreatment of teeth associated with apical
      periodontitis results in a success rate of 66 per cent, an uncertain healing rate
      of 11 per cent, and a failure rate of 23 per cent. Apical surgery results in a
      success rate of 59 per cent, an uncertain healing rate of 22 per cent, and a
      failure rate of 19 per cent. These figures are discussed with reference to the
      characteristics of the reviewed studies. It appears that many of the reviewed
      studies have lesser relevance today, due to the current technical improvements in
      both treatment and modalities.

PMID- 9170754
TI  - Simplified technique for custom tray fabrication.

PMID- 9170753
TI  - Occupational exposure to mercury in dentistry and dentist mortality.
AB  - In response to public concern, Health Canada recently conducted a review of
      amalgam safety and released a position statement entitled The Safety of Dental
      Amalgam. Essentially, the department has concluded that the levels of mercury
      absorbed by the body due to the release of mercury vapor from amalgam
      restorations, while detectable, do not approach those recognized to cause
      illness. It has therefore confirmed that amalgam restorations can be used safely
      in most patients, with some notable caveats. Despite Health Canada's position
      statement in support of amalgam, patient doubts about amalgam safety remain,
      including the tenuous hypothesized link between amalgam restorations and specific
      diseases. This article reviews the available studies of dentist mortality to
      identify possible links between mercury exposure and negative health effects. A
      lack of evidence to suggest a detrimental health outcome in dentists who are
      occupationally exposed to higher levels of mercury than their patients, and are
      known to have higher levels of mercury in their blood, provides an important
      reassurance concerning the safety of amalgam. The reviewed data indicates that
      the 10 leading causes of death in the United States and Canada are the same for
      both dentist and non dentist population groups, and that the percentage of deaths
      by the same cause are remarkably similar. By 1975, the year of the most recent
      U.S. study, the average age at death for white male dentists was about three
      years higher than for all adult white males. Although suicide standard mortality
      rates are known to be higher for dentists, suicide deaths have also been shown to
      be a factor in many other occupations, particularly those where there is easy
      access to drugs. Although updated actuarial data for dentist mortality are
      needed, the available data indicate no reduction in the life expectancy of
      practising dentists, nor any specific or disproportionate rates of disease
      associated with high mercury exposure. In fact, the available mortality studies
      are generally optimistic about the health of dentists, which should reassure
      patients about the safety of dental amalgam.

PMID- 9170755
TI  - The role of the community health nurse in military humanitarian operations:
      lessons from operation sea signal--Guantanamo Bay, Cuba.
AB  - The military humanitarian mission is an "Operation-Other-Than-War" with a goal of
      restoring or promoting the ability of a population to care for themselves (U.S.
      Army, 1990b). One of the primary foci of these operations is the medical care of
      the target populace. The elements and techniques of primary health care have been
      used for this purpose, especially as the situation of a population stabilizes and
      demands a community base for health care programs (Downing, 1989). The knowledge
      and expertise of a community health nurse is indispensable in both acute and
      chronic humanitarian situations in performing a comprehensive community needs
      assessment for the formulation of a community base for health care programs while
      facilitating a health care system that meets the overall needs of the population.
      The contributions of community health nurses assigned to Joint Task Force 160,
      during Operation Sea Signal, bear testimony as to the efficacy of such a
      "specialized" role in the care of displaced populations.

PMID- 9170757
TI  - The role of the community health nurse in the provision of care to youth gangs.
AB  - Youth gangs are a major public health care concern in the United States. The
      nursing profession is just beginning to recognize the needs of this special
      population. In this article, I present a general background of gangs in the
      United States. They have been a significant problem in society since the early
      decades of the 19th century; however, increasing crimes and high health risks
      make it important to seek some solutions. I present an example of a community
      health nurse who, as part of a Gang Reduction Interagency Partnership team made a
      difference. The need for more research is emphasized so that we may understand
      this population as well as address their health care needs and those of their
      families.

PMID- 9170756
TI  - A community-based nursing approach to the prevention of otitis media.
AB  - Otitis media (OM), a disease of the middle ear, is one of the most common
      diseases of childhood. Although the medical and surgical treatment of the disease
      by physicians is covered at length in the literature, information about the role
      of nurses in dealing with OM is scant. The purpose of this article is to propose
      a community-based nursing prevention plan for OM based on what is known about its
      prevalence and pathogenesis.

PMID- 9170758
TI  - The need for leadership and management training for community nurses: results of
      a Ugandan district health nurse survey.
AB  - A joint Ugandan-American team conducted a nonrandom convenience survey of 14
      Ugandan district health nurses from 12 of Uganda's 39 districts. The survey was
      designed to (a) identify what senior nursing personnel are actually doing in
      Ugandan districts, (b) determine whether these nurses believe that their nursing
      education prepared them for their roles, and (c) discover what these nurses
      believe should be added to the basic nursing curriculum to better prepare
      district nurses for their jobs. Supervision and general management made up the
      largest portion of the current district health nurse's actual and perceived
      roles. The nurses varied on how well their nursing education prepared them for
      their roles, but the majority voiced a need for further training in management
      skills. None of the nurses perceived herself to be a leader, and most displayed
      an inability to prioritize within their work settings.

PMID- 9170759
TI  - Evidence that therapy works in clinically representative conditions.
AB  - This article reports a secondary analysis of past therapy outcome meta-analysis.
      Fifteen meta-analysis provided effect sizes from 56 studies in previous reviews
      that met 1 of 3 increasingly stringent levels of criteria for clinical
      representativeness. The effect sizes were synthesized and compared with results
      from the original meta-analyses. Effect sizes from more clinically representative
      studies are the same size at all 3 criteria levels as in past meta-analyses.
      Almost no studies exist that meet the most stringent level of criteria. Results
      are interpreted cautiously because of controversy about what criteria best
      capture the notion of clinical representativeness, because so few experiments
      have tested therapy in clinical conditions, and because other models for
      exploring the generalizability of therapy outcome research to clinical conditions
      might yield different results.

PMID- 9170760
TI  - Therapy for youths with anxiety disorders: a second randomized clinical trial.
AB  - Ninety-four children (aged 9-13 years) with anxiety disorders were randomly
      assigned to cognitive behavioral treatment or waiting-list control. Outcomes were
      evaluated using diagnostic status, child self-reports, parent and teacher
      reports, cognitive assessment and behavioral observation: maintenance was
      examined using 1-year follow-up data. Analyses of dependent measures indicated
      significant improvements over time, with the majority indicating greater gains
      for those receiving treatment. Treatment gains returned cases to within
      nondeviant limits (i.e., normative comparisons) and were maintained at 1-year
      follow-up. Client age and comorbid status did not moderate outcomes. A
      preliminary examination of treatment segments suggested that the enactive
      exposure (when it follows cognitive-educational training) was an active force in
      beneficial change. Discussion includes suggestions for future research.

PMID- 9170761
TI  - Modeling relapse in unipolar depression: the effects of dysfunctional cognitions
      and personality disorders.
AB  - Survival analytic models were used to determine the effects of Axis II pathology
      and dysfunctional cognitions on depressive relapse in a sample of 50 depressed
      inpatients followed 33 to 84 months (M = 49.9) postdischarge. In analyses based
      on follow-up interview measures, expected remission duration among patients
      without personality disorders was approximately 7.4 times longer than among
      patients with Axis II comorbidity. Attributional style also accounted for unique
      variance in the relapse model, with adaptive positive event attributions
      inversely related to relapse probability. Neither dysfunctional attitudes nor
      negative event attributions were significantly related to relapse. Dimensional
      Axis II Cluster B and C pathology ratings were associated with decreased survival
      time, whereas Cluster A pathology was associated with increased survival. Among
      measures obtained during index hospitalization, only the dimensional rating of
      Axis II pathology was significantly predictive, with a cumulative 8% decrease in
      expected survival for each Axis II criterion item met.

PMID- 9170762
TI  - Gender differences in the relations between depressive symptoms and drinking
      behavior among problem drinkers: a three-wave study.
AB  - Prior research has suggested that the relation between depression and drinking
      behavior is stronger for women than for men. In a 3-wave study spanning 3 years,
      we examined the nature of reciprocal relations between depressive symptoms and
      drinking behavior among women (n = 207) and men (n = 207) seeking detoxification
      or referral services for their drinking problems. Latent variable structural
      equation modeling analyses revealed that more baseline depression was associated
      with less alcohol consumption 1 year later among women and men. However, later
      on, more depression predicted heavier alcohol consumption, but only among women.
      Among women and men, heavier alcohol consumption predicted more subsequent
      depression, although the timing of this effect differed by gender. Reciprocal
      effects between depression and drinking problems were found only among men.

PMID- 9170763
TI  - Cognitive-behavioral treatment of obsessive thoughts: a controlled study.
AB  - Twenty-nine patients with obsessive-compulsive disorder as diagnosed in
      accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd
      ed., revised; American Psychiatric Association, 1987) who did not have overt
      compulsive rituals were randomly assigned to treatment and waiting-list
      conditions. Patients in the treatment condition received cognitive-behavioral
      therapy consisting of a detailed explanation of the occurrence and maintenance of
      obsessive thoughts, exposure to obsessive thoughts, response prevention of all
      neutralizing strategies, cognitive restructuring, and relapse prevention.
      Compared with waiting-list patients, treated patients improved significantly on
      measures of severity of obsessions, current functioning, self-report obsessive
      compulsive symptoms, and anxiety. When waiting-list patients were subsequently
      treated, the combined group improved on all outcome measures. Treatment gains
      were maintained at 6-month follow-up. Results indicate that cognitive-behavioral
      therapy is effective in the treatment of patients with obsessive thoughts, a
      group that has often been considered resistant to treatment.

PMID- 9170764
TI  - The influence of psychological distress on use of genetic testing for cancer
      risk.
AB  - The recent identification of BRCA1, a breast cancer susceptibility gene, offers
      an unprecedented opportunity for high-risk individuals to learn whether they are
      genetically predisposed to develop breast or ovarian cancer. This study examined
      the relationships between psychological distress and use of BRCA1 testing by 149
      high-risk individuals from hereditary cancer families. After a baseline
      assessment of demographics, objective risk, cancer-specific distress, and global
      distress (depressive symptoms), study participants were offered the opportunity
      to receive genetic counseling and to learn whether they carry a mutation in the
      BRCA1 gene. Overall, 58% of study participants requested BRCA1 test results, and
      42% declined to learn their genetic status. After controlling for demographic
      factors and risk status, cancer-specific distress was significantly and
      positively related to BRCA1 test use, whereas global distress was unrelated to
      test use.

PMID- 9170765
TI  - Reinforcing operants other than abstinence in drug abuse treatment: an effective
      alternative for reducing drug use.
AB  - This study examines the effectiveness of using vouchers to reinforce either the
      provision of urine samples testing negative for illicit drugs (UA group) or the
      completion of objective, individually defined, treatment-plan-related tasks (TP
      group). A third group was assigned to the clinic's standard treatment (STD
      group). Participants were randomly assigned to groups after a 6-week baseline
      stabilization period. Urine specimens were collected thrice weekly throughout the
      study. In the UA condition, participants earned $5 (U.S. dollars) in vouchers for
      each drug-free urine submitted. In the TP condition, participants earned up to
      $15 in vouchers per week for demonstrating completion of treatment plan tasks
      assigned by their counselors. Contingencies were in effect for 12 weeks, after
      which all participants received the clinic's standard treatment. Urinalysis
      results indicate that the TP intervention was significantly more effective in
      reducing illicit drug use than either the UA or STD interventions. These effects
      were maintained with a trend toward continuing improvement for the TP groups even
      after contingencies were discontinued.

PMID- 9170766
TI  - Affect regulation and affective experience: individual differences, group
      differences, and measurement using a Q-sort procedure.
AB  - This article describes the development of, and preliminary findings with, the
      Affect Regulation and Experience Q-Sort (the AREQ), an observer-based assessment
      of affect regulation and experience. In Study 1, 31 clinicians provided Q-sort
      descriptions of 90 patients. Factor scores correlated in predicted ways with
      criteria such as suicide attempts and hospitalizations, as well as with
      clinicians' ratings of functioning in a variety of domains. Correlations between
      prototype Q-sorts and actual Q-sort profiles for patients sharing a diagnosis
      (dysthymia, borderline personality disorder, and narcissistic personality
      disorder) also provided evidence for convergent and discriminant validity. The
      data also suggested the importance of distinguishing 2 kinds of negative affect
      that have very different correlates. Study 2 showed that the AREQ can be applied
      reliably using an interview that avoids many of the problems of self-report.

PMID- 9170767
TI  - Self-statements of test-anxious children: thought-listing and questionnaire
      approaches.
AB  - Two methods of assessing cognition in high, moderate, and low test-anxious
      children, thought listing and self-statement questionnaire approaches, were
      investigated under naturalistic test-taking conditions. The amount of cognition,
      its content, and its relation to level of anxiety and task performance were
      examined. States of mind (SOM) analyses were performed. Furthermore, the
      comparability of findings from both methods was examined. Results showed that,
      relative to the questionnaire method, the thought-listing procedure
      underestimated positive and coping cognition. The benefits of the questionnaire
      approach were seen in the power of its scores to predict task performance.
      Implications for cognitive assessment and treatment of anxious children are
      discussed.

PMID- 9170768
TI  - Are weight concerns predictive of smoking cessation? A prospective analysis.
AB  - Participants in an 8-session, community based smoking cessation intervention
      rated whether they would stay quit if they experienced weight gain. The majority
      reported that they would not relapse to smoking, even after a 20-lb, (9.07-kg)
      weight gain. Those who were weight concerned were more likely to be female, to
      weight less and be normal or underweight, and to report chronic dieting. This
      group was also significantly less likely to be abstinent posttreatment, and at
      the 1-, 6- and 12-month follow-ups. Individuals presenting for formal smoking
      cessation interventions may be less weight concerned than the general population
      of smokers. However, weight-concerned smokers who do present for treatment are
      less likely to quit smoking. Implications for recruitment and intervention are
      discussed.

PMID- 9170769
TI  - Family experience of barriers to treatment and premature termination from child
      therapy.
AB  - Barriers to participation in treatment were proposed as a basis for dropping out
      of treatment among children seen in outpatient therapy. Families (N = 242) of
      children referred for treatment for oppositional, aggressive, and antisocial
      behavior participated. The main findings were that (a) barriers to participation
      in treatment contributed significantly to dropping out of therapy; (b) perceived
      barriers to treatment were not explained by family, parent, and child
      characteristics that also predicted dropping out; and (c) among families at high
      risk for dropping out of treatment, the perception of few barriers attenuated
      risk. Parent perceptions of the difficulties of participating in treatment
      (including stressors and obstacles associated with treatment, perceptions that
      treatment is not very relevant, and a poor relationship with the therapist)
      influenced who dropped out.

PMID- 9170770
TI  - The impact of service characteristics on functional outcomes from community
      support programs for persons with schizophrenia: a growth curve analysis.
AB  - A total of 172 individuals diagnosed with a schizophrenia spectrum disorder were
      followed for 36 months in 3 distinct models of community-based care. Functional
      outcome data gathered every 6 months were combined with service implementation
      data to test hypotheses concerning the impact of service characteristics on
      prospective client outcomes. The results using hierarchical linear modeling
      supported associations between the intensity, specificity, and longitudinality of
      services and improved client outcomes. Specifically, more intense services were
      associated with higher levels or rates of improvement on all indices of clinical
      and psychosocial functioning. The specificity results suggested that services
      needed to be targeted to specific areas of functioning in order for improvement
      to occur. The effect of longitudinality was contingent on the outcome domain
      examined.

PMID- 9170771
TI  - Evaluating an intervention for homeless persons: results of a field experiment.
AB  - An intensive case management intervention for homeless persons was evaluated by
      random assignment of 202 cases (involving 213 adults and 70 children) to the
      intervention or a control group. Full follow-up data (4 interviews: at baseline
      and at 6-, 12-, and 18-month follow-ups) were available on 98 cases (105 adults
      and 37 children). The follow-up rates for the 2 groups were not significantly
      different. Based on 13 repeated measures analyses, there were 3 statistically
      significant linear time effects (indicating overall change across the follow-up
      period) and 3 linear Time x Condition interactions (indicating differential
      change over time for intervention vs. control participants). Regardless of
      condition, adult participants improved in terms of their experience of
      homelessness, as well as on physical health symptoms and stressful life events.
      Condition x Time interactions indicating positive intervention impact were
      observed on the quality of housing environments, stressful life events, and
      interviewer ratings of psychopathology.

PMID- 9170772
TI  - Patterns of services and consumer outcome in an intensive case management
      program.
AB  - This study examined the patterns of services provided to individuals with serious
      and persistent mental illness during their first year in an intensive case
      management program. Services in 10 content areas were examined, and patterns for
      more versus less "successful" individuals were compared. Differences emerged for
      services focusing on family and housing, suggesting that the need for community
      support services influences the need for continued intensive case management.
      Linear reductions in rehabilitation services suggest that such services may
      indeed be effective early in the treatment process. Finally, differences among
      case managers in service patterns for 5 of the 10 content areas suggest that case
      managers play an important role in determining the course of treatment.

PMID- 9170773
TI  - Stress, maternal distress, and children's adjustment following immigration: the
      buffering role of social support.
AB  - This study examined, in the context of a stress-buffering model, the relationship
      of certain family-level variables to children's adjustment after immigration.
      Immigrant Chinese mothers from Hong Kong completed questionnaires regarding
      postmigration stress, personal distress, perceived social support, and their
      child's adjustment. Another adult also provided child behavior ratings. Analyses
      revealed that, for boys, family stress and maternal distress were significant
      predictors of child problems and that maternal support buffered the association
      between family stress and child problems. Contrary to expectation, the
      relationship between maternal distress and boys' problems was stronger at higher
      levels of maternal support. For families of girls, although there were
      significant relationships between the predictors and child behavior, no stress
      buffering was evident. Cultural explanations are discussed.

PMID- 9170774
TI  - HIV risk reduction for incarcerated women: a comparison of brief interventions
      based on two theoretical models.
AB  - Although female inmates are seropositive at rates that exceed those of male
      inmates, few studies, have evaluated HIV risk reduction interventions for
      incarcerated women. This demonstration project compared an intervention based on
      social cognitive theory against a comparison condition based on the theory of
      gender and power. Incarcerated women (N = 90) were assessed at baseline,
      postintervention, and again 6 months later. Both interventions produced increased
      self efficacy, self-esteem, Attitudes Toward Prevention Scale scores, AIDS
      knowledge, communication skill, and condom application skills that maintained
      through the 6-month follow-up period. Participants in the intervention based on
      social cognitive theory showed greater improvement in condom application skills,
      and women in the program based on the theory of gender and power evidenced
      greater commitment to change. The results suggests brief interventions in prison
      settings are feasible and beneficial. However, it is not yet known whether the
      changes will generalize into the natural environment after the women's release
      into the community.

PMID- 9170775
TI  - Contribution of the therapeutic alliance to outcome in active versus control
      psychotherapies.
AB  - Few studies have examined the role of the therapeutic alliance scores in active
      versus control psychotherapies. Using data from a randomized clinical trial of
      psychotherapy and pharmacotherapy for cocaine dependence, it was found that
      therapeutic alliance scores were rated as significantly more positive in
      cognitive-behavioral treatment than clinical management, a psychotherapy control
      condition. However, level of the therapeutic alliance was associated with outcome
      for the control but not the active psychotherapy. These data suggest that control
      conditions, which are intended to control for common factors of psychotherapies
      such as the therapeutic alliance, may exert their effect on outcomes primarily
      through the level of those common factors.

PMID- 9170776
TI  - Clinician reliability and accuracy in judging appropriate level of care.
AB  - Accurately assigning children to the most appropriate level of care is widely
      recognized as important. Managed care companies conduct utilization reviews in
      which they monitor the level of care to which clients are assigned using written
      placement criteria. However, no research has examined the ability of clinicians
      to perform this task. In the present study, 47 child and adolescent clinical
      profiles consisting of 48 variables were developed. Eighteen clinicians, trained
      to use their agency's level-of-care guidelines, made level-of-care decisions on
      these profiles. Their interjudge reliability in assigning a child to an
      appropriate level of care was close to zero (kappa = .07). There was a small,
      statistically significant correlation between client placement and actual
      placement, but chance-corrected agreement between client placement and actual
      placement was very low (kappa = .09). Implications of these findings for clinical
      research, practice, policy, and training are discussed.

PMID- 9170777
TI  - Decreasing the burden of measurement.

PMID- 9170778
TI  - Measuring the perception of choices in the nursing home.
AB  - The purpose of this study was to measure the perception of choices among elders
      who live in a nursing home. The perception of choices, defined as a subjective
      appraisal of alternatives as understood by the individual, includes the freedom
      to make decisions, individuality of judgment, and availability of options. The
      instrument--Perception of Choices in a Nursing Home (PCL)--is a 10-item
      dichotomous scale designed for administration to frail elderly. A study with
      three phases involved 228 elderly in 19 different nursing homes. The results of
      principal component's factor analysis supported the presence of one dimension
      interpreted as having choices. The internal consistency reliability was a = .84,
      n = 99; and a = .74, n = 129. Low mental status did not affect internal
      consistency reliability but affected retest reliability, r = 67. The PCL
      correlated significantly with depression, r = .31, p = .0001, and powerlessness,
      .36, p = .005.

PMID- 9170779
TI  - Reliability, construct validity, and subscale norms of the Brief Symptom
      Inventory when administered to bereaved parents.
AB  - The Brief Symptom Inventory (BSI) was administered to parents (N = 260; 171
      mothers and 89 fathers) whose adolescent and young adult children died
      unexpectedly and violently by accident, homicide, or suicide. Summary statistics
      and reliability coefficients (Cronbach's alpha) for the nine subscales and the
      Global Severity Index were calculated. A comparison of means and standard
      deviations confirmed the expectation that this sample is dramatically different
      from the normative American community standard. Raw scores for the subscales were
      transformed into standardized T scores and critical values for a screening
      heuristic presented. An attempt to obtain construct validity using factor
      analysis suggested that a five-factor solution provided a description of this
      population of bereaved parents that is more insightful than the nine standard
      subscales of the BSI. Implications for both clinicians and future research are
      discussed.

PMID- 9170780
TI  - The Postpartum Support Questionnaire: reliability and validity.
AB  - Support has been found to be related to perinatal health, resulting in the
      development of the Postpartum Support Questionnaire based on the four categories
      of support (informational, material, emotional and comparison) identified by
      House (1981) and Cronenwett (1985). Data from four studies (N = 207) provided
      evidence of the psychometric properties of the instrument. Internal consistency
      reliability was demonstrated (alpha = .90 to .94 for total instrument). Test
      retest reliability ranged from .69 to .79 for total scores and .30 to .79 for for
      categories of support. Measures of concurrent validity with the Personal Resource
      Questionnaire .85 were .42 and .48 at 6 and 8 weeks postpartum. Confirmatory
      factor analysis using LISREL 7 supported the four categories of support, but the
      use of these factors separately remains to be demonstrated.

PMID- 9170781
TI  - Exercise-induced hyperthermia may prevent accurate core temperature measurement
      by tympanic membrane thermometer.
AB  - The purpose of this study was to assess the effect of exercise-induced
      hyperthermia on brain and deep trunk temperature measurement in order to
      determine the optimal temperature site of the body for varying nursing practices
      in outpatient clinical settings. Eight women, 18 to 50 years old (30.9 +/- 12.6;
      mean +/- SD), participated in the study. Subjects were asked to perform their
      regular aerobic exercise in a natural environment while body temperature (ear and
      rectal) and heart rate (HR) were measured simultaneously and repeatedly before,
      during, and after exercise. Glass mercury rectal thermometers were used for
      measurement of deep trunk temperature, an infrared tympanic membrane thermometer
      for measurement of brain temperature, and a portable heart rate monitor for
      monitoring heart rate. Rectal temperature was higher than ear temperature for all
      but one of the 40 pairs of observation. The time pattern varied for the two modes
      of temperature (F = 9.67; df 4,28; p < .001). Rectal temperature changed over
      time (F = 7.86; df 4,28; p < .002), and ear temperature did not (F = 1.5; df
      4,28; p = .25), indicating that ear temperature did not respond to exercise.
      While rectal temperature was strongly correlated with HR (r = .60), ear
      temperature did not correlate either with rectal temperature (r = .02) or with HR
      (r = .08). Thus deep trunk temperature responds to exercise at moderate levels.
      On the other hand, ear temperature does not increase due to exercise. Ear
      temperature is not a valid indicator of trunk temperature during and immediately
      after exercise.

PMID- 9170782
TI  - Preliminary testing of the Long-Term Quality of Life (LTQL) instrument for female
      cancer survivors.
AB  - The purpose of this study was to develop a quality of life instrument for long
      term female cancer survivors. A factor analysis (n = 188) of 34 items resulted in
      the Long-Term Quality of Life (LTQL) instrument. Internal consistency was high
      for the four subscales: somatic concerns (alpha = .86), spiritual/philosophical
      views of life (alpha = .87) fitness (alpha = .92) and social support (alpha =
      .88). These four factors are congruent with Ferrell's four theoretical domains of
      quality of life developed for women with breast cancer. Content validity was
      supported through interrater agreement of subscale items. Significant
      correlations between the LTQL and the CaRES, an established measure of quality of
      life, support the concurrent validity of the LTQL. Construct validity was
      supported by differential subscale scores according to demographic and health
      status data. Although the LTQL retained all of Ferrell's four domains of quality
      of life (physical, psychological, social, and spiritual) within one instrument,
      individual items reconfigured to suggest an overlapping of domains for the long
      term female cancer survivor. This research suggests that the LTQL warrants
      further testing and may be a useful measure of quality of life in long-term
      female cancer survivors.

PMID- 9170783
TI  - Applying the Cantril methodology to study self-esteem: psychometrics of the Self
      Anchoring Self-Esteem Scale.
AB  - The importance of the construct of self-esteem is evidenced by its extensive
      inclusion in prior research as a measure of well-being or adaptation to illness.
      Despite the construct's importance, current measures of self-esteem are
      inadequate when used among populations experiencing illnesses, such as cancer.
      Use of an alternative measure of self-esteem is proposed which addresses
      limitations of existing measures. The Self-Anchoring Self-Esteem Scale (SASES) is
      an adaptation of Cantril's methodology used to study quality of life, which
      requires individuals to subjectively define high and low endpoints of a 10-point
      ladder prior to providing numerical ratings. Data collected from three cross
      sectional studies involving four samples of healthy individuals and women with
      cancer supported psychometric properties of the scale.

PMID- 9170784
TI  - Unfinished business of the 20th century. United Nations Children's Fund (UNICEF)

PMID- 9170785
TI  - Scapegoating the elderly: new voices, old theme.

PMID- 9170786
TI  - A survey of state health department compliance with the recommendations of the
      Institute of Medicine report, The Future of Public Health.
AB  - We repeated a survey of state health agencies (SHAs) designed to ascertain the
      extent that the recommendations of the Institute of Medicine's report, The Future
      of Public Health, have been implemented. This survey was originally done in 1989
      and we repeated the same survey in 1996. While there has been progress in some of
      the recommendations, such as a separate department of health, agreed-upon public
      health duties, outreach, infrastructure, and scope of responsibilities, there
      continue to be problems with the implementation of some of the recommendations.
      For example, the proportion of agencies reporting that the core public health
      function of policy development is extant has actually declined since 1989. There
      continue to be problems, with developing linkages of public health with
      environmental health and mental health, with strengthening the public health
      infrastructure, and with expansion of the scope of public health
      responsibilities. We encourage the continued monitoring of the implementation of
      the IOM recommendations.

PMID- 9170787
TI  - Organized labor and health reform: union interests and the Clinton plan.
AB  - The fringe benefits on which most Americans have come to rely for health
      insurance constitute a critical foundation of both the postwar regime of labor
      relations and the distinctive American welfare state. One legacy of these
      complementary regimes was a wide variety of institutional commitments and
      organizational arrangements in the area of health benefits. That diversity of
      experiences created a range of political incentives for unions when it came to
      health reform. Thus, when President Clinton proposed a "managed competition"
      approach to health reform in 1993, divisions within the labor movement
      contributed to the ineffectiveness of the campaign mounted by supporters of the
      effort. This article reviews the development of a "private-sector welfare state"
      in the United States, documents the range of accompanying institutional
      arrangements, and suggests how they may have shaped the political calculations of
      certain unions when faced with the Clinton White House's reform proposal.

PMID- 9170788
TI  - Content analysis of coverage of alcohol control policy issues in black-oriented
      and mainstream newspapers in the U.S.
AB  - We conducted a content analysis of alcohol control policy issues in Black
      oriented and mainstream newspapers in the United States from 1993 to 1995, using
      computerized content analysis methods. The specific purpose of our study was to
      compare differences in coverage of alcohol control policy issues in Black
      oriented and mainstream newspapers. Fifteen Black-oriented and 12 mainstream
      newspapers were selected and analyzed. The number of policy paragraphs per year
      and the number of paragraphs in different policy thematic categories per year
      were examined. Regional differences in coverage of alcohol policy themes were
      examined for selected policies in mainstream newspapers. We found more
      similarities than differences in coverage of alcohol policy issues in Black
      oriented and mainstream newspapers. Limiting the marketing/advertising and
      promotion of alcohol products was the most widely covered alcohol control policy
      issue over the three-year period in both Black-oriented media and mainstream
      newspapers. There were some important differences in coverage of alcohol policy
      issues. While economic alcohol policy issues were covered extensively in
      mainstream newspapers, these issues received far less attention in Black-oriented
      newspapers. Findings suggest that certain alcohol control policies may have less
      salience in African-American communities than in other communities.

PMID- 9170789
TI  - Setting the stage for health impact assessment.
AB  - Defining health impact assessment as any combination of procedures or methods by
      which a proposed policy or program may be judged as to the effect(s) it may have
      on the health of a population, we make recommendations about how to evaluate the
      health impact of all government-initiated policies. Such health impact cannot be
      assessed in the absence of a conceptual or organizing framework that provides the
      requisite guideposts--population health goals and targets. Health impact
      assessment offers an approach to ensuring that governments' program and policy
      initiatives align, or are congruent with, the agreed-upon health goals. It
      suggests that proposed national policies should be supported or resisted on the
      basis of their probable influence on the health of populations. In the current
      Canadian national policy framework, however, there are no underpinnings on which
      to situate such a process. The specification of consensus goals and objectives
      with measurable targets can provide the requisite guideposts and benchmarks for
      health impact assessment. Such an undertaking can set the stage and provide the
      necessary foundation for an effective health impact assessment process.

PMID- 9170790
TI  - Expanding the physician-substitute concept to oral health care practitioners.
AB  - This position paper proposes the development of an intermediate level
      practitioner to increase access to primary oral health care and to maximize cost
      benefit factors. The proposal is built upon research which has demonstrated the
      feasibility of preparing baccalaureate hygienists to serve as the counterpart to
      the physician assistant or nurse practitioner. The role of the primary oral
      health care practitioner would involve locating underserved or non-user groups,
      assessing oral health needs, referring to appropriate care providers, and
      providing primary care traditionally provided by dentists. Promotion of the
      intermediate oral practitioner would require policy to halt erosion of the
      infrastructure of university-based dental hygiene education, the allocation of
      nationally funded financial incentives, and specified modifications in the
      current health care system.

PMID- 9170791
TI  - South Africa's new national drug policy. Interview by Daphne Fresle.

PMID- 9170792
TI  - Examining the cut of the emperor's new clothes.

PMID- 9170793
TI  - Vision, learning and dyslexia. A joint organizational policy statement of the
      American Academy of Optometry and the American Optometric Association.
AB  - 1. Vision problems can and often do interfere with learning. 2. People at risk
      for learning-related vision problems should be evaluated by an optometrist who
      provides diagnostic and management services in this area. 3. The goal of
      optometric intervention is to improve visual function and alleviate associated
      signs and symptoms. 4. Prompt remediation of learning-related vision problems
      enhances the ability of children and adults to perform to their full potential.
      5. People with learning problems require help from many disciplines to meet the
      learning challenges they face. Optometric involvement constitutes one aspect of
      the multidisciplinary management approach required to prepare the individual for
      lifelong learning.

PMID- 9170794
TI  - Evaluating the value of low-vision services.
AB  - BACKGROUND: Low-vision care is a widely accepted and valued service provided by
      many optometrists. As in other areas of health care, evaluation of the outcome of
      low-vision care is increasingly necessary so it can be properly positioned in the
      health care delivery system. METHODS: This article reviews the literature
      relating to the prevalence of low vision, its impact on affected individuals, and
      how low-vision intervention affects those with visual impairments. This review
      considers the ways in which the impact of low-vision care has been evaluated.
      RESULTS: The existing literature demonstrates that low-vision intervention can be
      highly valued by low-vision patients and can have a significant impact on an
      individual's daily life and activities. Evaluating this impact is a significant
      challenge-particularly if the goal is to gauge the outcome of low vision care as
      broadly as possible. CONCLUSIONS: Evaluation of health-related quality of life is
      a desirable option for evaluation of outcomes, and the application of quality of
      life instruments to the visually impaired population is necessary. There remain
      unresolved issues of optometric research that need to be addressed.

PMID- 9170795
TI  - Endotoxin concentration in contact lens storage cases.
AB  - BACKGROUND: The contamination of contact lens storage cases by gram-negative
      bacteria has been associated with ulcerative keratitis. This study investigated
      the concentration of endotoxin, a substance produced by gram-negative bacteria,
      in contact lens cases. METHODS: The limulus amebocyte lysate (LAL) test was used
      to measure the concentration of endotoxin in the storage cases of 27 contact lens
      wearers. The units of concentration used were endotoxin units per ml (EU/ml). The
      type of storage solution used by each patient, as well as other aspects of lens
      care and use, were recorded. RESULTS: Twenty-one storage cases--78% of those
      tested--contained measurable amounts of toxin. Two cases contained extremely high
      concentrations of endotoxin: 60 EU/ml and 300 EU/ml. Both cases were from persons
      using Opti-Free. Cases from six persons using Opti-Free accounted for five of the
      top seven endotoxin concentrations when cases were ranked on that basis. Fewer
      hours of daily lens wear and lower lens age were also possibly associated with
      higher concentrations of endotoxin, although those associations may have resulted
      by chance (p = 0.057 and p = 0.095, respectively). CONCLUSIONS: The LAL test was
      useful in estimating the degree of contamination of cases by gram-negative
      bacteria. Most cases contained measurable amounts of endotoxin, indicating at
      least some contamination by gram-negative bacteria. The effectivity of Opti-Free
      in inhibition of bacterial growth in contact lens cases should be investigated
      further.

PMID- 9170796
TI  - Prevalence of vision problems in an indigent urban population.
AB  - BACKGROUND: Low-income individuals may encounter difficulties in gaining access
      to routine health care. Certain clinics operate to serve indigent people. The
      University of Missouri-St. Louis, School of Optometry, in conjunction with New
      Life Evangelistic Center, offers routine eye care in such a clinic. METHODS: A
      retrospective epidemiologic analysis of 2 years of eye clinic records from the
      center was performed to determine the prevalence of vision anomalies in the study
      population and the benefit of the availability of this care. RESULTS: The mean
      patient age was 37.8 years, with a high percentage of the patients being black
      males. Ninety-five percent of the patients required a change in spectacle
      prescription, improving acuities from an average of 20/70 O.D. and 20/70(-3) O.S.
      to 20/25(+1) O.D. and 20/25 O.S. This result indicates a statistically
      significant improvement in exit visual acuities as compared with entrance visual
      acuities (p < 0.0001). The mean spherical refractive error was -0.77 +/- 2.50 D
      O.D. and -0.77 +/- 2.45 D O.S. The mean cylinder in each eye was -1.00 +/- 0.75
      D. Most cylinders were oriented with-the-rule Ocular disease was present in 11.9%
      of the patients; systemic disease in 10.4% of patients. Referrals to other health
      care practitioners were made in 5.9% of cases. CONCLUSIONS: This study
      demonstrates that indigent patients receive a useful and needed service from
      clinics that provide routine eye care to this population.

PMID- 9170797
TI  - Effect of contralateral fog during refractive error assessment.
AB  - BACKGROUND: When assessing refractive error using static retinoscopy, it is
      conventional to fog the contralateral eye by approximately 2.00 D to prevent a
      blur-driven accommodative response stimulating consensual accommodation in the
      tested eye. However, the effect of higher amounts of contralateral fog (e.g., in
      a moderate-to-high uncorrected myopic individual) during refractive error
      assessment is unclear. METHODS: We assessed the refractive state in 16 visually
      normal myopic subjects while fogging the contralateral eye between zero and 6.00
      D, in 1.00 D increments. Retinoscopy was simulated by shining a streak
      retinoscope light into the right eye, while simultaneously measuring the
      refractive state of this eye objectively. RESULTS: No significant change in mean
      refractive state was observed for up to 5.00 D of contralateral fog. But, 6.00 D
      of contralateral fog produced a significant mean increase in the myopic direction
      of 0.13 D. Also, in three subjects, a myopic shift of approximately 0.60 D was
      recorded after the introduction of 6.00 D of contralateral fog. Nevertheless, the
      magnitude of these largest shifts in refractive error are still smaller than the
      previously reported degree of repeatability of static retinoscopy. CONCLUSIONS:
      Since large amounts of contralateral fog produced only small and clinically
      insignificant changes in the refractive state, the practitioner merely needs to
      ensure that the nontested eye is indeed fogged. The magnitude of fog present will
      have only a minimal effect on the final result.

PMID- 9170798
TI  - Understanding angioid streaks.
AB  - BACKGROUND: Angioid streaks are defined as a series of linear, cracked-line
      dehiscences of Bruch's membrane, with secondary changes in the retinal pigment
      epithelium and choriocapillaris. They may be progressive or degenerative, with
      varied presentation, color, distribution, and retinal involvement. METHODS: The
      epidemiology, pathophysiology, diagnosis, and management of angioid streaks are
      described. In addition, the systemic diseases most commonly associated with the
      disease are reviewed. RESULTS: Optometrists need to be able to differentially
      diagnose angioid streaks and to refer for evaluation of underlying systemic
      disease. CONCLUSIONS: Angioid streaks are considered a rare disorder, associated
      with pseudoxanthoma elasticum, Paget's disease of the bone, sickle
      hemoglobinopathies. Marfan syndrome, and Ehlers-Danlos syndrome. Ocular
      complications include subretinal choroidal neovascular membrane formation.
      Clinicians should be aware of the disease's subtle ocular appearance, its
      association with systemic diseases, its potential for producing subretinal ocular
      complications, and correct management protocols and treatments.

PMID- 9170799
TI  - Mirror-image optic nerve dysplasia with associated anisometropia in identical
      twins.
AB  - BACKGROUND: Monozygotic (MZ) or "identical" twins arise from a single fertilized
      egg, which divides into two embryos at an early stage of development. As a
      result, MZ twins have identical genomes and are always of the same sex. METHODS:
      A case of optic nerve hypoplasia and anisometropia, in association with mirror
      image presentation in a set of 12-year-old identical twins, is reported. The
      monozygotic twinning event responsible for identical twins--as well as the rare
      phenomenon of mirror imaging--is described. RESULTS: The combined occurrence of
      anisometropia and optic nerve hypoplasia in mirror-image presentation in a set of
      monozygotic twins provides a unique opportunity to study the genetic versus
      environmental influences on the development of optic nerve hypoplasia.
      CONCLUSIONS: Although the cause of optic nerve hypoplasia remains unclear, its
      associated mirror-image presentation in this case suggests a possible genetic
      predisposition.

PMID- 9170800
TI  - Too hazardous?

PMID- 9170801
TI  - No health risk?

PMID- 9170802
TI  - Medicinal leeches: ancient therapy is a source of biotech drugs.
AB  - Hirudin analogs have been shown to be inhibitors of thrombin with many potential
      uses. These agents appear to have advantages over conventional anticoagulant
      agents such as heparin. The hirudin compounds do not require a cofactor to work,
      have consistent dose-dependent effects, act directly on thrombin, are highly
      specific, and have little to no toxicity.

PMID- 9170803
TI  - Beyond anecdote: OAM investigates alternative therapies.

PMID- 9170804
TI  - Pushing the envelope: VA's mail-service operation.

PMID- 9170805
TI  - Specializing opens doors.

PMID- 9170806
TI  - Pharmaceutical care in New Zealand: customizing the blueprint.

PMID- 9170807
TI  - Thalidomide. A surprising recovery.
AB  - The epidemic of birth defects in Europe in the early 1960s attributed to
      thalidomide led to stringent and unprecedented drug safety requirements in many
      countries. No definitive mechanism of action has been determined for the
      biological activities associated with thalidomide. Food and Drug Administration
      and congressional concerns about the handling of clinical investigations of
      thalidomide led to sweeping new regulations for clinical trials. Thalidomide is
      currently being used clinically to treat such conditions as cachexia associated
      with HIV and cancer, mycobacterial disease, and autoimmune diseases.

PMID- 9170808
TI  - On-line DUR messages: pharmacists' attitudes and actions in response.
AB  - Community pharmacists are encountering on-line drug utilization review (DUR)
      messages with increasing frequency. DUR messages are sent by third party claims
      processors and generated by pharmacies' in-house computer systems. The purpose of
      this study was to ascertain community pharmacists' attitudes toward on-line DUR
      messages and the actions most often taken by pharmacists after receiving these
      messages. A 28-item questionnaire was mailed to a random sample of 1,500
      community pharmacies throughout the United States. Four hundred twenty-seven
      questionnaires were returned and analyzed (a 28.5% response rate). The majority
      of respondents were male pharmacists practicing in independent community
      pharmacies in cities with populations of less than 50,000. The low response rate
      from chain pharmacies was an important limitation of this study. The results
      indicate that pharmacists find DUR messages related to medication overuse and
      drug interactions to be the most useful. Interventions are not performed for all
      DUR messages received, and interventions usually consist of telephoning
      physicians and talking to patients. This study demonstrates that many types of
      DUR messages are useful to pharmacists; however, additional research and further
      refinement of DUR messages appear necessary.

PMID- 9170809
TI  - Readiness for change: implications for patient care.
AB  - The strategic position of pharmacists within the community allows frequent
      interactions with many patients, thus making pharmacists potentially valuable
      resources for assisting patients in making behavioral changes regarding adherence
      to treatment. The Transtheoretical Model is a behavior-change model that provides
      a functional approach through which pharmacists can help patients to reach
      specific behavioral goals. The model is described and stage-specific examples of
      patient-pharmacist dialogue are provided to show how the model may be used to
      promote progression through the stages.

PMID- 9170810
TI  - A community-pharmacy-based callback program for antibiotic therapy.
AB  - OBJECTIVE: To develop a telephone callback program to reinforce basic patient
      counseling given at the time of dispensing. DESIGN: At the time each prescription
      was filled, the pharmacist or pharmacy student recorded the patient's name,
      telephone number, date of birth, diagnosis, drug regimen, prescriber, relevant
      concurrent medications, initial comments, and date. Follow-up phone calls were
      then made when appropriate to assess patient progress in therapy. RESULTS:
      Telephone assessment of 521 patients revealed that while 51.1% reported their
      condition had improved, 15.1% had worsened. Of the 79 therapeutic failures, 47
      patients repeated the initial therapy or received a different antibiotic without
      another physician visit, 32 were referred back to their physicians, and 5 each
      resulted from noncompliance or adverse effects. CONCLUSIONS: A callback program
      is an effective and inexpensive mechanism for assessing and improving drug
      therapy outcomes.

PMID- 9170811
TI  - Barriers to the use of pharmacy services: the case of ethnic populations.
AB  - The barriers that minority populations face with respect to the use of pharmacy
      services may differ from those faced by other populations. A pretested
      questionnaire was administered to a convenience sample of 96 Vietnamese residents
      of a mid-size Midwestern city. Perceptions of five common barriers to pharmacy
      services were investigated. Financial difficulty (47%), language (25%), and
      physical illness (14%) were the most serious barriers to pharmacy services,
      followed by transportation and unemployment. These researchers propose seven
      broad strategies that pharmacists might use to minimize the effect of the
      barriers. The use of these strategies could benefit patients by improving their
      health, and increase opportunities for pharmacists to provide pharmaceutical care
      to the rapidly growing Vietnamese community and other ethnic populations.

PMID- 9170812
TI  - Survey on unclaimed prescriptions in a community pharmacy.
AB  - OBJECTIVE: To quantify the number of unclaimed prescriptions, document the
      reasons patients did not claim prescriptions, investigate the effect of telephone
      contact on the pickup rate, and document the types of medications involved and
      the frequency of this type of non-compliance. DESIGN: A total of 549 unclaimed
      prescriptions were evaluated during a nine-month study. Pharmacy students
      contacted patients whose prescription orders had been dispensed but not claimed.
      Patients contacted by telephone were asked why they had not claimed their
      prescriptions. The types of medications involved were documented, and a follow-up
      check was made of the patient's profile on the pharmacy computer system to
      determine whether the telephone contact affected the pickup rate. RESULTS:
      Reasons given for not claiming the prescriptions included: transfer to another
      pharmacy, prescription was forgotten, the patient no longer wanted or needed the
      prescription because they had medication left over, or patient decided they did
      not need the medication. Telephone contact had minimal impact on the compliance
      rate of this patient group. The most common unclaimed medication categories were
      anti-infectives, cough and cold/allergy medications, and birth control/hormones.
      CONCLUSIONS: Patients cited many reasons for not picking up their medication.
      Follow-up telephone calls did not increase the number of prescriptions picked up
      by patients in this study.

PMID- 9170813
TI  - Alzheimer's disease: an overview for the pharmacist.
AB  - Alzheimer's disease (AD) occurs more frequently in women, with an incidence
      greater than expected from longevity alone--a finding possibly related to reduced
      estrogen levels. The epidemiology, societal costs, clinical presentation,
      pathophysiology, etiology, and treatment of AD are reviewed. At present, only two
      drugs, tacrine and donepezil, are approved for treatment of AD. These drugs
      enhance central cholinergic activity by inhibiting cholinesterase. The goal of
      current drug development research is to halt progress of AD, and efforts are
      underway to discover ways to restore neuronal activity via neurotrophins and to
      prevent neuronal loss. Pharmacists are well positioned to assist AD patients (in
      the early stages) and caregivers by encouraging early intervention and by
      presenting realistic expectations about the disease and its treatment. A number
      of easily accessible resources for health care providers and consumers are
      presented.

PMID- 9170814
TI  - Automated medication dispensing devices.

PMID- 9170815
TI  - Hope: a cardinal virtue of the pharmaceutical care pilgrimage.

PMID- 9170816
TI  - Effects of glucose on placental hormones in the human term placenta in vitro.
AB  - Glucose intake during pregnancy results in a decrease in endogenous insulin-like
      growth factor binding protein-1 (IGFBP-1). However, the exact role of glucose on
      placental secretion of IGFBP-1 is unclear. This study was designed to investigate
      the direct effects of glucose on the production of IGFBP-1 and other placental
      hormones, using an isolated placental preparation. Using the dual recirculating
      perfusion system for an isolated human placenta lobule, a total of 43 experiments
      were performed over a duration of 6 hours. Twenty placentae were perfused with a
      medium containing 141 +/- 10 mg/dL (7.83 +/- 0.56 mmol/L) glucose (group I) and
      23 placentae with 242 +/- 12 mg/dL (13.43 +/- 0.67 mmol/L) glucose (group II).
      Levels of insulin, glucose, lactate, insulin-like growth factor (IGF-I), IGFBP-1,
      human placental lactogen (hPL) and beta-human chorionic gonadotropin (beta-hCG)
      were measured at 30 minute intervals during perfusion. Insulin and IGF-I were
      barely detectable in the perfusates and their levels were not modulated by
      glucose. IGFBP-1 was predominantly detected in the maternal rather than the fetal
      compartment of the placental circulation. Glucose increased the levels of IGFBP-1
      in the maternal circulation in groups I and II during the first two hours of
      perfusion (188 +/- 58% and 193 +/- 31%, respectively). However, during the
      subsequent 4 hour period, the increase in IGFBP-1 concentration was significantly
      higher in group II (926 +/- 427%) than in group I (428 +/- 216%) (p < 0.05).
      There was no difference in the levels of hPL or beta-hCG between the two groups
      in the maternal circulation. Thus, glucose stimulates the production of IGFBP-1
      in the maternal circulation of a placenta in vitro. This increase in IGFBP-1 by
      glucose in vitro, as opposed to the decrease of IGFBP-1 in vivo, may be due to a
      lack of circulatory maternal insulin in the isolated placental preparation. These
      results also suggest that there may be a functional barrier within the placenta
      that prevents an increase in the level of IGFBP-1 in the fetal circulation.

PMID- 9170817
TI  - Serum 2',5'-oligoadenylate synthetase concentrations in acute and chronic
      hepatitis C.
AB  - To clarify the role of in vivo interferon activation in the recovery from acute
      hepatitis C and in the prediction of responses to interferon-alpha treatment in
      chronic hepatitis C, we measured concentrations of 2',5'-oligoadenylate
      synthetase in the serum of 14 patients with well-documented acute post
      transfusion hepatitis C and 40 patients with histologically confirmed chronic
      hepatitis C. In the latter group, 16 received interferon-alpha treatment, while
      no specific treatment was given to patients with acute hepatitis C. Serum
      activity of 2',5'-oligoadenylate synthetase was measured in duplicate by
      radioimmunoassay. Four out of the 14 patients with acute hepatitis C recovered,
      and hepatitis in the remaining 10 became chronic. Serum 2',5'-oligoadenylate
      synthetase concentration in the acute stage of hepatitis was above 200 pmol/dL in
      all four patients who recovered and in only of two of the remaining 10 patients
      (p < 0.02, Fisher's exact test). The 16 chronic hepatitis C patients who received
      interferon-alpha treatment were classified into sustained responders, relapsed
      responders and nonresponders, as judged by their responses to the treatment.
      Among the three groups, there was no significant difference in the mean
      concentrations of 2',5'-oligoadenylate synthetase either before the treatment or
      in the peak concentrations during the treatment. We conclude that activation of
      in vivo interferon in the acute stage favors recovery from acute hepatitis C, and
      2',5'-oligoadenylate synthetase concentration cannot predict the responses to
      interferon-alpha treatment in patients with chronic hepatitis C.

PMID- 9170818
TI  - Allogeneic bone marrow transplantation for Philadelphia chromosome-positive
      chronic myelogenous leukemia in childhood.
AB  - Allogeneic bone marrow transplantation (BMT) offers the only potential for long
      term control of chronic myelogenous leukemia. From November 1992 to August 1994,
      we prospectively studied five pediatric patients with Philadelphia chromosome
      positive chronic myelogenous leukemia, a unique finding in Taiwan, who were
      treated with allogeneic BMT at different stages of the disease. Their ages at
      diagnosis ranged from 2 to 10 years. Four donors were HLA-matched siblings and
      the other was an HLA-matched unrelated donor. All patients received busulfan (4
      mg/kg/day for 4 days) followed by cyclophosphamide (60 mg/kg/day for 2 successive
      days) as the conditioning regimen. Engraftment was documented within 22 days
      after transplantation in all five patients. Two out of the four patients in the
      sibling donor group, both of whom had BMT in the first chronic phase, achieved
      event-free survival after follow-up for 41 months and 17 months. The other two
      patients, who had BMT in the second lymphoblastic crisis and the second chronic
      phase, died within 6 months after transplantation due to lymphoid blastic crisis
      and complication of cytomegaloviral pneumonitis, respectively. The patient who
      received marrow from the unrelated donor underwent BMT in the accelerated phase
      and died within 6 months after transplantation due to myeloid blastic crisis. In
      conclusion, allogeneic BMT performed in the first chronic phase of childhood
      Philadelphia chromosome-positive chronic myelogenous leukemia seems to have
      better results than BMT after the first chronic phase.

PMID- 9170819
TI  - Endotracheal tube size selection guidelines for Chinese children: prospective
      study of 533 cases.
AB  - Appropriate selection of the size of an endotracheal tube (ETT) for use in
      children is important both in general anesthesia and critical care practice. Past
      published data on guidelines for selecting ETT size in children are based on
      Caucasian measurements. As body build is generally different in Chinese children
      compared with Caucasians of the same age group, guidelines for Chinese children
      are needed. The aim of this study was to determine guidelines for ETT size
      selection by recording and comparing age, body weight, length, head girth and
      circumference of the right fifth finger of the child. Correlations between
      internal diameter (ID) of the chosen ETT and the child's data were calculated and
      compared. In this study, 533 Chinese children. American Society of
      Anesthesiolgists class I or II, aged from 3 months to 6 years, undergoing oral
      intubation for general anesthesia for minor pediatric surgery were enrolled. Our
      results showed that body length (height) had the best correlation to the size of
      an uncuffed oral ETT. Through stepwise regression, a formula. ETT ID = 2 + (body
      length (cm)/30), was obtained.

PMID- 9170820
TI  - Importance of sputum differential cell counting in the diagnosis of airway
      diseases.
AB  - We examined the sputum of 114 subjects by noninvasive methods (voluntary coughing
      or induced cough with hypertonic saline) to determine whether sputum examination
      could be used to separate patients with episodic wheezing, dyspnea or cough of
      unknown origin into different diagnostic categories. An increased percentage of
      sputum eosinophils was seen in 92% (48/52) of asthmatics, 36% (9/25) of patients
      with chronic obstructive pulmonary disease (COPD) and 28% (7/25) of chronic
      coughers, but not in any of the 12 patients with congestive heart failure (CHF).
      Eight patients with combined symptoms of COPD and asthma (mixed COPD subgroup)
      showed above average diurnal peak expiratory flow variation (10.3 +/- 2.1% vs 2.5
      +/- 1.4%, p < 0.05) and an above average percentage of sputum eosinophils (19.8
      +/- 9.1 vs 2.1 +/- 3.2, p < 0.01) than those in the pure COPD group. After
      therapeutic corticosteroid trial, all of the mixed COPD patients and six of the
      17 pure COPD patients were steroid responders. Seven of the 25 chronic coughers
      had sputum eosinophilia, but no asthmatic symptoms. The cough symptoms subsided
      in five of these seven patients after steroid treatment but not in the other 18
      chronic coughers. Further study is indicated to determine if simple eosinophilic
      bronchitis is an early stage of asthma. In conclusion, sputum differential cell
      counting is a useful noninvasive diagnostic tool in differentiating diseases with
      episodic wheezing or chronic cough.

PMID- 9170821
TI  - Constitutive fatty acid and enzyme profiles of Mycobacterium species.
AB  - Sixty-one strains of Mycobacterium tuberculosis complex and 47 strains of
      nontuberculous mycobacteria were analyzed for fatty acids and enzyme profiles.
      Cellular fatty acids were extracted from bacteria, methylated and analyzed by gas
      liquid chromatography operated either manually (Perkin-Elmer) or by the automatic
      Microbial Identification System. The major cellular fatty acids in all
      mycobacterial species were C16:0 and C18:1. Tuberculostearic acid was found in
      all species with the exception of Mycobacterium gordonae. The fatty acids with a
      carbon-length longer than 20 could be detected only by conventional gas
      chromatography. Strains of M. tuberculosis had a high ratio of C26:0 to C24:0,
      and a relatively low ratio of C14:0 to C15:0. For determination of branched-chain
      fatty acids, the MIS provided more definitive results. The data indicated that
      the fatty acid profiles could provide rapid species identification. The results
      of the enzyme profile analysis using API-ZYM strips showed 39 different patterns
      from 59 strains of M. tuberculosis, and 41 different patterns from 46
      nontuberculous mycobacteria strains, suggesting that enzyme profiles can also be
      used for strain characterization within the same species.

PMID- 9170822
TI  - Surgical experience with Salmonella-infected aneurysms of the abdominal aorta.
AB  - Five patients, aged between 64 and 75 years with Salmonella-infected abdominal
      aortic aneurysms were surgically treated between 1993 and 1995 at the National
      Cheng Kung University Hospital. Cultures of aneurysmal wall tissue and blood
      yielded Salmonella enteritidis Group B in three patients and Salmonella
      choleraesuis in the remaining two. All patients presented with fever and
      abdominal or back pain. Pulsatile masses were noted in only two patients.
      Infrarenal abdominal infected aneurysms were demonstrated by computed tomography
      and aortography in each patient. The five patients underwent aneurysmal resection
      with in situ graft reconstruction from 1 to 20 days after the diagnosis was made.
      The graft was wrapped with an omental pedicle. Duodenal repair was performed in
      one patient due to an aortoduodenal fistula found during surgery. He died 19 days
      after surgery because of duodenal leakage and uncontrolled sepsis. Four patients
      survived and remained well 11 to 34 months (mean, 25 mo) after surgery.
      Postoperatively, only one patient developed adhesion ileus and required
      enterolysis. Parenteral antimicrobial therapy was continued in all patients after
      surgery for 2 to 4 weeks; only one patient had an additional 4 months of oral
      antibiotics. Although the number of patients was small, the survival rate was
      high, at 80%. Our experience suggests that Salmonella-infected aneurysms of the
      abdominal aorta can be successfully treated by resection of the aneurysm with
      extensive debridement followed by in situ graft interposition with omentum
      wrapping. Once diagnosed, the patients should be scheduled for surgery as soon as
      possible. Antibiotics should be continued parenterally for at least 2 to 4 weeks
      postoperatively. While long-term suppressive antibiotic therapy is usually
      recommended, it might not be essential with our surgical approach.

PMID- 9170823
TI  - Reconstruction for sequelae of septic hip in children.
AB  - Sequelae of septic hip in children may develop either due to inadequate
      management or neglect in the acute stage. We treated 13 patients (13 hips) with
      late sequelae of septic hip by reconstruction procedures, from 1985 to 1992. The
      mean age of the patients was 6.1 years. Their initial bony deformities were all
      beyond Hunka's classification type IIB. All of them had problems of hip
      instability and leg length discrepancy. With the intention to reestablish
      containment of the hip joint, open reduction, femoral osteotomy and pelvic
      osteotomy were performed. Four patients, all beyond Hunka type IV, had secondary
      surgery for hip resubluxation. Leg length discrepancies were corrected by valgus
      osteotomy and limb lengthening. At an average follow-up of 6.3 years, all
      remodeled hips were stable. Early reconstruction is recommended to stabilize the
      hip joint and restore the normal hip center for bone development. The leg length
      discrepancies were corrected by an Ilizarov limb lengthening procedure at a later
      stage.

PMID- 9170824
TI  - Treatment of congenital pseudarthrosis of the tibia with the Ilizarov method.
AB  - Congenital pseudarthrosis of the tibia (CPT) is a difficult orthopedic problem.
      Many modalities of treatment have been used but none provide comprehensive
      treatment with highly satisfactory results. We reviewed the surgical management
      and results of eight consecutive patients with CPT treated with the Ilizarov
      technique for nonunion, angulation, leg length discrepancy and valgus ankle
      between 1988 and 1992. The median age at the time of Ilizarov treatment was 1.8
      years (range, 0.4-20.1 yr). Primary union at the pseudarthrosis site was achieved
      in five of the eight patients. After a median follow-up period of 5.2 years
      (range, 3.0-6.2 yr), final union at the pseudarthrosis site was achieved in seven
      of the eight patients (union rate, 87.5%). However, nonunion persisted at the
      distraction site in one patient. In the six patients who achieved union and
      functional recovery, the median number of total surgeries was four; there were
      two residual deformities. Leg length discrepancy was corrected in these six
      patients to less than 1.7 cm. Six out of the eight patients were satisfied with
      the results. In general, the treatment course was lengthy with numerous
      complications, especially in young children. The Ilizarov technique, with its
      ring design, simultaneously addresses several problems associated with CPT, and
      may provide a comprehensive treatment for CPT with promising results. Combination
      treatment with other methods is necessary.

PMID- 9170825
TI  - Randomized comparison of misoprostol and dinoprostone for preinduction cervical
      ripening and labor induction.
AB  - This study attempts to evaluate the clinical effects of prostaglandin (PG) E
      analogues in preinduction cervical ripening and labor induction and to compare
      the perinatal outcomes of these medications. Sixty women with term singleton
      pregnancies were randomized to receive dinoprostone vaginal tablets (group I) or
      misoprostol vaginal tablets (group II). The Bishop scores were evaluated before
      drug insertion and every 4 hours during induction. Clinical data and perinatal
      outcomes were also recorded. There were no significant differences in the
      preinduction conditions on mean initial Bishop scores between these two groups.
      Twelve hours after drug insertion, the mean Bishop scores were significantly
      better in group II (9.7 +/- 3.1 vs 7.3 +/- 2.5, p < 0.05). The mean time from
      insertion to delivery was shorter in group II (16.5 +/- 2.7 h vs 25.7 +/- 3.8 h,
      p < 0.001). There were no significant differences in spontaneous labor rate, need
      for oxytocin augmentation, type of delivery, and Doppler flow velocity waveforms
      of the umbilical artery. The average number of doses given per patient was 1.8 +/
      1.4 in group II vs 2.7 +/- 0.3 in group I (p < 0.05). The perinatal outcome was
      similar in the two groups. In conclusion, misoprostol not only appears to be a
      safe and effective agent for cervical ripening and labor induction but is also
      more efficient than dinoprostone.

PMID- 9170826
TI  - Benign recurrent intrahepatic cholestasis.
AB  - Benign recurrent intrahepatic cholestasis is a rare disorder of unknown etiology
      and has not yet been reported in Taiwan. We report a case with a typical clinical
      course. A 17-year-old Taiwanese boy had three episodes of pruritus and jaundice
      from February 1993 to July 1995, each lasting 3 to 4 months. Jaundice
      spontaneously subsided and he was symptom-free during periods of remission. A
      fourth episode of pruritus began in July 1995, with jaundice developing later and
      lasting for 3 months. Laboratory tests revealed direct hyperbilirubinemia.
      Endoscopic retrograde cholangiopancreatography showed normal intra- and
      extrahepatic biliary trees. Light microscopy of a liver biopsy sample revealed
      hepatocellular and canalicular cholestasis with bile retention in the Kupffer
      cells. Benign recurrent intrahepatic cholestasis was diagnosed after exclusion of
      other possible causes of jaundice. The patient made an uneventful recovery.

PMID- 9170827
TI  - Microbiologic and histologic diagnosis of histoplasmosis in Taiwan.
AB  - Histoplasmosis is one of the most common opportunistic fungal infections in
      immunocompromised patients in endemic areas. We report the first two
      microbiologically documented cases of histoplasmosis in Taiwan. The first
      patient, with acquired immunodeficiency syndrome and a depleted CD4+ lymphocyte
      count, presented with a history of prolonged fever, papular skin rashes,
      pancytopenia and elevation of liver enzymes. He was diagnosed and treated
      initially for systemic toxoplasmosis, but the microbiologic and pathologic
      findings of the autopsied specimens disclosed disseminated infection caused by
      Histoplasma capsulatum. The second patient, an elderly man receiving
      corticosteroids for adrenal insufficiency, manifested with laryngeal
      histoplasmosis and was successfully treated with ketoconazole.

PMID- 9170828
TI  - Transaortic patch angioplasty for left main coronary artery occlusion.
AB  - Isolated total occlusion of the left main coronary artery is rare, and may be
      conventionally treated by standard bypass surgery. We describe a 54-year-old
      woman with isolated left main coronary artery disease presenting as unstable
      angina of 1 week's duration. She was treated with transaortic autologous
      pericardial patch angioplasty. Postoperative coronary angiography showed a widely
      patent left main coronary artery. She was angina-free 5 months postoperatively.
      In selected patients, this technique offers a valuable alternative to coronary
      artery bypass with the advantage of restoring more physiologic perfusion to the
      coronary tree.

PMID- 9170829
TI  - Thrombolytic therapy for mitral valve thrombosis.
AB  - A 44-year-old man with a St. Jude mitral valve was admitted because of
      progressive pulmonary edema. He was diagnosed with prosthetic heart valve
      thrombosis (PHVT) based on the findings of "muffled" prosthetic valve clicks.
      Doppler echocardiographic evidence of severe mitral stenosis and transesophageal
      echocardiographic evidence of limited mitral valve motility. Because the patient
      hesitated to undergo our recommended surgical treatment, he was immediately
      treated with intravenous recombinant tissue plasminogen activator (100 mg over 3
      h) followed by heparinization. Two hours after the thrombolytic therapy, the
      prosthetic valve clicks became clearly audible and his congestive symptoms were
      dramatically improved. Follow-up echocardiography no longer-showed significant
      mitral valve obstruction. A transient cerebral ischemic attack occurred at the
      end of thrombolytic therapy but there were no neurologic sequalae. The patient,
      on warfarin therapy, was well at follow-up 8 months after discharge. Surgical
      intervention has long been the standard therapy for patients with PHVT. Our case
      experience suggests that thrombolytic therapy may be considered as an effective
      alternative to surgical intervention for selected patients with PHVT. In this
      report, we also review the current literature regarding the indications,
      effectiveness and safety of thrombolytic therapy in PHVT.

PMID- 9170830
TI  - Minority physicians: educating and preparing for the changing face of health
      care.

PMID- 9170831
TI  - Chaos, criticality, and public health.
AB  - Self-organized criticality offers more than a descriptive model or a doomsday
      forecast. We have tried to suggest that it is a paradigm for understanding the
      interconnections between apparently complex processes. At best, it suggests a
      method for finding the pressure points that can be used to bring unstable systems
      of public health services into greater levels of stability. The model enjoins us
      to understand that our goal is not to achieve equilibrium--that perfect match
      between the demand for health services and its delivery--but rather stability
      (or, more precisely, metastability). As is true of the sandpile, our systems of
      public health are constantly evolving. If we are correct, then the mechanism
      driving this ostensibly complex pattern of change and growth reflects the
      existence of simpler and, hopefully, more manageable processes. By monitoring
      these processes, it may be increasingly possible to adapt to change and even
      manage it effectively.

PMID- 9170832
TI  - Correlation of digital rectal examination, prostate specific antigen, and
      transrectal ultrasound in prostate carcinoma in African Americans.
AB  - Since there is general agreement that screening for prostate cancer should be
      carried out, at least for high-risk individuals, there should be little debate
      that African-American men should be screened. Current screening guidelines
      include the two most cost-effective methods of early detection, digital rectal
      examination and prostate specific antigen. The use of transrectal ultrasound and
      guided biopsy improves the yield. This article reports on the findings of 50
      African-American patients with prostatic carcinoma diagnosed by sonographically
      guided biopsy in a single, community urology practice. Overall, prostate specific
      antigen was elevated in 94%, digital rectal examination was positive in 60%, and
      transrectal ultrasound was positive in 78%. A focal hypoechoic lesion was
      demonstrated in 58%. When the site of tumor, as specified in the pathology
      report, was correlated with the findings on digital rectal examination and
      transrectal ultrasound, both digital rectal examination and transrectal
      ultrasound were positive in 45%. Transrectal ultrasound was positive when digital
      rectal examination was negative in 30%. Digital rectal examination was positive
      when ultrasound was not in 14%. Random biopsy revealed areas of carcinoma that
      were not detected by digital rectal examination nor ultrasound in 40%. We
      conclude that even though random biopsy significantly improves the detection of
      prostate carcinoma, sonographic guidance is beneficial to systematically biopsy
      the gland and to avoid omission of characteristic lesions during random
      samplings.

PMID- 9170833
TI  - Patterns of use of a free nicotine patch program for Medicaid and uninsured
      patients.
AB  - This study assessed the use and effectiveness of a free nicotine patch program
      among Medicaid and uninsured smokers. Patterns of patch use, associated behaviors
      with quit attempt, side effects, and self-reported abstinence from smoking for 6
      months were evaluated prospectively among patients from five urban family
      practice offices and a nicotine dependence clinic located in a comprehensive
      cancer center in Western New York. Results indicated that the majority of
      participants used the program as intended, and 90% of the participants found the
      patch useful in their quit attempt. Fourteen percent of participants were
      abstinent for 6 months or more. We found no support for inappropriate use of
      transdermal nicotine patches among patients with no health insurance or those on
      Medicaid. Transdermal nicotine patches are an effective cessation aid for
      smokers. Given the tall of the consequences of smoking on health costs, barriers
      to access to effective treatment for smoking cessation among individuals covered
      by Medicaid for health insurance need to be eliminated.

PMID- 9170834
TI  - Stress-related disorders in African-American children.
AB  - Children exposed to traumatic stress are vulnerable to a variety of stress
      related disorders other than classical post-traumatic stress disorder. Several
      case histories are presented to illustrate some of the diversity of how traumatic
      stress may manifest in children. African-American children are the main focus of
      this article as political, economic, social, and morbidity and mortality
      indicators suggest that African-American children are at high risk for exposure
      to potentially traumatic stressors. Different presentations of traumatic, stress
      are discussed in an effort to broaden our understanding of the outcome of
      traumatic stress to fully help traumatized children.

PMID- 9170835
TI  - Founders-Sumner lecture.
AB  - The revolution in patient care financing and in the structure and changing scope
      of the health service system calls for leaders in health care to address existing
      challenges in the health delivery system. Medical leadership cannot ignore, much
      less resist, the challenges inherent in the flux and dynamic changes going on in
      the medical care/health sciences environment. Some of these changes are fueled by
      fundamental advancements in science and technology. Other developments are fueled
      by political, demographic, economic and social forces. This article highlights
      some of these challenges and urges the medical leadership to assume the
      obligation to assure quality of health-care services and not allow it to be over
      shadowed by market forces.

PMID- 9170836
TI  - Cervical prolapse complicating pregnancy.
AB  - Uterine cervical prolapse concurrent with pregnancy is rare. This article reports
      three cases of second-degree cervical prolapse during pregnancy. Two women
      developed prolapse in the late second trimester while one women had preexisting
      prolapse. Both women with prolapse developing during midpregnancy were treated
      unsuccessfully with a vaginal pessary to maintain cervical placement. Premature
      labor occurred in both of these women, resulting in one preterm birth. Although
      cervical prolapse is rarely encountered in pregnancy, the threat of preterm labor
      and delivery warrants close observation.

PMID- 9170837
TI  - South African health-care system at the crossroads.

PMID- 9170838
TI  - [Plenary session of the Scientific Association of Surgeons of the Ukraine.
      Odessa, 15-17 May 1996. Abstracts].

PMID- 9170839
TI  - [Merits and demerits of automation ophthalmic instruments].

PMID- 9170840
TI  - [Expression of matrix metalloproteinases and tissue inhibitor of
      metalloproteinase by myofibroblasts--morphological study on corneal wound
      healing].
AB  - The matrix metalloproteinases (MMPs) and the tissue inhibitor of
      metalloproteinases (TIMPs) regulate the extracellular matrix and are important in
      the process of connective tissue remodeling. In this study, we investigated the
      expression of MMPs and TIMP-2 by myofibroblasts (MF) originating from keratocytes
      during the healing of alkali-burned and lacerated rabbit corneas. In light and/or
      electron microscopic immunohistochemistry, the MMP-1, 2, 9 and TIMP-2 antibodies
      reacted with MF in both types of corneal wounds. The clear expression of MMP-1
      and the relatively faint immunoreaction of MMP-2 were observed in both types of
      healing from one week after wounding, while MMP-9 appeared from 3 weeks after
      injury. In addition, the levels of MMP-2 and 9 were increased from 4 weeks after
      alkali-burned injury. The clear expression of TIMP-2 was observed from 1 week
      after both types of wounds. These findings indicate that MF is deeply involved in
      degrading some of the key matrix proteins (such as type I collagen), and may play
      an important role in tissue remodeling in corneal wounds through production of
      MMPs and TIMP.

PMID- 9170841
TI  - [Accumulation of 14C-cystine in inherited cataractous rat lens].
AB  - This study was designed to investigate the formation of mixed disulfides of
      protein and glutathione (GSH) in the cataractous lens. We compared the changes in
      accumulation of 14C-cystine in cultured inherited cataractous rat lens (ICR/f)
      during cataractogensis with those in Wistar strain rats. The accumulation of 14C
      cystine in water insoluble protein (WIP) of the lens was increased, especially in
      lens recognized cataract. The radioactivity accumulated in the WIP was released
      by incubation with 2-mercaptoethanol (2-ME), dithiothereitol (DTT) and GSH. The
      accumulation of 14C-cystine in WIP was inhibited by pretreatment with DTT. The
      existence of some materials in the lens-which combined with S-S compounds became
      clear. A large part of the materials is present in WIP which is increased along
      with the lens opacification. We surmised that the accumulation of 14C-cystine was
      related to the reaction of protein-glutathione disulfide (PSSG).

PMID- 9170842
TI  - [Glycohistochemical analysis of rat eyelid epithelium].
AB  - The glycoconjugates in eyelids of adult rats were examined by lectin
      histochemistry and in situ hybridization histochemistry. Since Maackia amurensis
      lectin II and jacalin bound to the cell membranes of basal and apical epithelial
      cells, sialic acid alpha 2,3 galactose (Gal) beta 1,3 N-acetylgalactosamine
      (GalNAc) sequence is present in the glycoconjugates of their cell membranes.
      Peanut agglutinin bound to the cell membranes of spinous cells in the middle of
      the epithelium, suggesting that Gal beta 1, 3 GalNAc sequence is present in their
      glycoconjugates. The mRNA of Gal beta 1,3 GalNAc alpha 2,3-sialyltransferase was
      detected in the cytoplasm of the epithelial cells other than the basal cells.
      This observation suggests that sialoglycoconjugates may be newly synthesized in
      the spinous and apical cells, while the glycoconjugates in the cell membranes of
      basal cells may be produced at an early stage of development and are stable
      without turnover.

PMID- 9170844
TI  - [Correlation analysis between visual acuity and sitting postural parameters of
      young students].
AB  - The relationship between failing eyesight and the sitting posture of young
      students while studying was studied quantitatively. Among the 19 students who
      participated in this study, 9 were classified as emmetropic and 10 were myopic.
      The mean age was 13.2 +/- 2.2 (mean +/- standard deviation) years. Viewing
      distance, neck angle, viewing angle, vertical gaze direction, and ocular surface
      area while studying were measured from the lateral and frontal view images of
      video recordings of the posture. Viewing distance, accommodative power, neck
      angle, viewing angle, near point, and log transformed visual acuity showed
      significant differences between these two groups (p < 0.001). Viewing distance of
      myopes (15.0 +/- 1.9 cm) (mean +/- standard desviation) is shorter than that of
      emmetropes (30.2 +/- 4.1 cm). Accommodative power of myopes was lower than that
      of emmetropes. Correlation analysis revealed that the viewing distance of
      students significantly correlates to neck angle, viewing angle, accommodative
      power, near point, and visual acuity (p < 0.01). It can be surmised that the
      failing eyesight of young students results from postural problems such as
      shortness of viewing distance and increased neck flexion.

PMID- 9170843
TI  - [Cataracts occur in patients with atopic dermatitis when the serum IgE
      increases].
AB  - The serum-IgE (sIgE) levels of eight patients with cataract complicated by atopic
      dermatitis (atopic cataract) who had undergone cataract surgery were reported.
      Five of them were diagnosed as having cataract the first visit to our eye clinic.
      The other three cases did not show cataract at the first visit but developed it
      later. The average sIgE of the five cases with cataract was 25,478 +/- 15,936
      (mean +/- standard deviation) iu/ml whereas that of the latter three cases
      without cataract, at the first visit was 4,638 +/- 1,810 iu/ml. The average sIgE
      of these three cases when their cataracts were diagnosed first went up to 13,210
      +/- 5,574 iu/ml. These results suggested that a high level of sIgE may be a
      warning of the appearance of atopic cataract.

PMID- 9170845
TI  - [Effects of topical application of adrenergic agents on refraction and
      accommodation].
AB  - In an attempt to clarify the functional role of adrenergic receptors on
      accommodation, effects of various adrenergic agents on the state of accommodation
      were studied. Fifty-two emmetropic normal subjects (age: 19-28 y) participated in
      this study. We examined the effect of the alpha agonist phenylephrine
      hydrochloride (5%), the alpha 1 antagonist adrenergic bunazosin hydrochloride
      (0.1%), the beta antagonist timolol maleate (0.5%), the beta 2 antagonist
      betaxolal hydrochloride (0.5%), and the beta agonist isoproterenol hydrochloride
      (3%). Using an infrared optometer, the refraction, far point and near point of
      accommodation, resting point of accommodation (empty-field accommodation and dark
      focus of accommodation), and accommodative adaptation were measured before and
      after topical application of various adrenergic agents. Application of bunazosin
      slightly but significantly decreased the near point of accommodation.
      Isoproterenol evoked a hyperopic shift on the far point of accommodation. None of
      the agents had any effect on the resting point of accommodation. Accommodative
      adaptation was increased by timolol and betaxolol, and decreased by
      isoproterenol. We surmised that beta adrenergic agents exerted an indirect
      influence on the parasympathetic nervous system. The activation of beta receptors
      produced a hyperopic shift on the far point of accommodation and decreased
      accommodative adaptation, which suggests that activation of adrenergic receptors
      may reduce parasympathetic activity, hence affecting the state of accommodation.

PMID- 9170846
TI  - [Treatment of full-thickness macular holes with autologous serum].
AB  - A total of 29 eyes in 28 patients with stage 2 to 4 idiopathic full-thickness
      macular hole were treated with autologous serum. Autologous serum (20-30
      microliters) was placed over the macular hole followed by injection of 16%
      perfluoropropane gas. Postoperatively, twenty-eight eyes (97%) had flattening of
      the macular hole, and the hole was invisible in 27 eyes (93%). Twenty-two eyes
      (76%) showed visual improvement of at least two lines or more. Preoperative
      factors such as good visual acuity, earlier stage, and younger age were
      correlated with postoperative good visual acuity. These results suggest the
      benefit of autologous serum in the treatment of full-thickness macular holes.

PMID- 9170847
TI  - [Detection of resting state of accommodation by accommodative microfluctuation].
AB  - Accommodative microfluctuations were recorded when the subjects were looking at a
      stable target. The waves of the accommodative microfluctuation were analyzed by
      fast Fourier transform. When accommodation was in a resting state, the high
      frequency components were minimized. This suggested that the resting state of
      accommodation might be measured when the subject was looking at a target. At a
      little distance from the resting state of accommodation, the high frequency
      components were maximized. This might suggest a negative accommodation.

PMID- 9170848
TI  - [Aging and the focal macular electroretinogram].
AB  - Focal macular electroretinograms (MERGs) were recorded with a fundus monitor
      through an infrared television fundus camera in 112 eyes of 112 normal subjects
      (68 males, 44 females), using three stimulus spots 5 degrees, 10 degrees, and 15
      degrees in diameter. The amplitude and the implicit time of the a-wave, h-wave,
      and oscillatory potentials (OPs), and the ratio of amplitude of the b-wave to the
      a-wave (b/a ratio) at each stimulus spot were compared in terms of aging and sex.
      The amplitude of all components decreased significantly (p < 0.01-0.05) after the
      fifth decade, and there was a tendency for OPs to decrease more than the a-wave
      and b-wave. There was no significant effect of age on the h/a ratio and the
      implicit time of each component. The ratio of increase of amplitude to the
      enlargement of stimulus spot showed no significant changes with age. There was no
      significant difference in each component in terms of amplitude and implicit time
      with sex. The decrease of amplitude of all components after the fifth decade
      suggests aging of the macular cones. The tendency toward decreasing OPs also
      suggests aging of the inner retina in the macular region. The proportional
      changes of amplitude recorded with three different sizes of stimulus spots
      indicate that there is no significant effect of aging on the fovea, parafovea, or
      perifovea.

PMID- 9170849
TI  - [Studies on ocular positions at close distance with a new system of measuring
      ocular positions].
AB  - The purpose of our study was to develop a new system of measuring ocular
      positions and to assess its clinical applicability. This system is derived from
      that of the Hess coordimeter and is used at a distance of 40 cm. Our system
      enables us to distinguish tropia from phoria by testing the ocular positions both
      with and without a fusional target which can be seen by both eyes. All devices
      are installed in one structure and it can be used in a lighted room. The system
      was checked in 10 normal subjects by plotting the data of the charts onto a graph
      and deriving a static eye position curve. There was no significant vertical
      deviation, and there was an exodeviation of 5.32 +/- 3.78 (mean +/- standard
      deviation) degrees without a fusional target, but no significant deviation
      occurred when the fusional target was lighted. In 37 of the 38 patients with
      ocular motor disturbance, the results with this system corresponded well with
      those obtained by the Hess coordimeter or prism cover test. One particular case
      with extraocular myositis involving more than two extraocular muscles showed an
      atypical complicated pattern. We believe that our system is simple and easy for
      clinical evaluation of ocular movement abnormality in ophthalmic diagnosis.

PMID- 9170850
TI  - [Glycohistochemical analysis of seborrheic keratosis in eyelids].
AB  - The glycoconjugates of seborrheic keratosis in the eyelids were examined by in
      situ hybridization histochemistry using cRNA probes for sialyltransferase (ST)
      and lectin histochemistry. We considered that the cells, which expressed both
      cytoplasmic distribution of ST-mRNA and binding of lectins specific for sialic
      acids to the cell surfaces, were actively producing sialoglycans. We also
      considered that the cells whose surfaces were stained with the lectins without
      cytoplasmic distribution of ST-mRNA have completed the synthesis of sialoglycans.
      These viewpoints suggest that the O-linked sialoglycan, whose turnover-rate is
      slow, may be distributed over the cells of the thickened spinocellular layer in
      the tumor of seborrheic keratosis and involved in its pathomechanism. It also
      appears that the turnover rate of the terminal sialic acids in the N-linked
      glycan in the spinocellular layer may be fast.

PMID- 9170851
TI  - [The effect of age on short-wavelength sensitive cone electroretinograms and long
      and middle-wavelength sensitive cone electroretinograms].
AB  - We studied the effect of age on short-wavelength sensitive cone electroretinogram
      (S-cone ERG) and long-and middle-wavelength sensitive cone ERG (LM-cone ERG)
      using a contact lens electrode with a built-in light-emitting diode. We recorded
      ERGs in 31 pseudophakic subjects to avoid the effect of yellowing in human
      crystalline lens. The intensities of our stimuli were on the asymptote of the
      intensity-response curve. We performed linear regression analysis against age on
      the S-cone ERG b-wave (S-b), and the LM-cone ERG a-, b- and d-waves (LM-a, LM-b,
      LM-d). We found significant age-dependent reduction in the amplitude of S-b, LM
      a, and LM-d, significant prolongation in the peak time of LM-b and LM-d, and
      significant increase in the b/a ratio of the LM-cone ERG, but no significant age
      correlation between the peak time of S-b and LM-a and the amplitude of the b
      wave. Our results provide evidence that age-related changes in S- and LM-cone
      systems begin in the twenties in humans. Furthermore, a significant increase of
      the b/a ratio suggests that off-bipolar cells are more vulnerable to aging than
      on-bipolar cells.

PMID- 9170852
TI  - [A case of dermatomyositis with severe retinopathy in a patient who died of acute
      interstitial pneumonia].
AB  - Sight threatening ocular complications are rare in adult patients with
      dermatomyositis. We encountered a 52-year-old female with dermatomyositis who had
      severe visual disturbance and rapidly progressive intersitial pneumonia. She was
      admitted to our hospital because of skin erythema, general fatigue, mild fever,
      and severe bilateral visual disturbance. Rentinal hemorrhages, cotton wool spots,
      and macular edema were observed in her fundus at the first ophthalmic
      examination. A diagnosis of dermatomyositis was made because of the myogenic
      pattern of her electromyogram, elevation of serum creatine kinase, and skin
      lesions. Oral prednisolone treatment was started and the retinopathy was
      improved, but was complicated by acute interstitial pneumonia. The interstitial
      pneumonia was not respond to steroid pulse therapy with methylprednisolone, and
      the patient died of respiratory failure on the 47th day after the onset of visual
      symptoms. In adult dermatomyositis patients, the complication of severe
      retinopathy should be considered as a risk factor for rapid progress of
      interstitial pneumonia.

PMID- 9170853
TI  - [Comparison of retinal breaks between patients with atopic dermatitis and
      mentally retarded patients with self-inflicted ocular injury].
AB  - We compared the distribution of retinal breaks in retinal detachment between
      patients with atopic dermatitis (AD) and mentally retarded patients who had self
      inflicted ocular injury (MR). The cases of AD were 16 eyes in 14 patients (six
      males and eight females, ranging in age from 15 to 52 years, mean 24.5) and the
      cases of MR were 6 eyes in 5 patients (5 males, ranging in age from 14 to 25
      years, mean 20.2). There was no corneoscleral laceration in either group. In the
      patients with AD, 14 (87.5%) of 16 eyes had retinal breaks at the vitreous base,
      and 21 (87.5%) of 24 retinal breaks in 16 eyes were at the vitreous base. In the
      patients with MR, five (83.3%) of 6 eyes had retinal breaks at the vitreous base
      and 6(66.7%) of 9 retinal breaks in 6 eyes were at the vitreous base. In both
      groups, ciliary epithelial breaks and peripheral retinal tears were frequently
      observed, suggesting that retinal detachment in AD has a pathophysiology similar
      to traumatic retinal detachment with repeated ocular contusion (self-inflicted
      injury).

PMID- 9170854
TI  - [Extended total aortic arch replacement involving the proximal descending aorta
      through a median sternotomy].
AB  - From January 1986 to September 1995, total aortic arch replacement (TAR) for
      aortic dissection was performed using selective cerebral perfusion in 151
      patients. In 18 patients, the surgical procedures of extended aortic arch
      replacement (EAR) involving the proximal descending aorta through a median
      sternotomy were applied. To evaluate the outcome of EAR, the early and late
      results were compared with those of non-extended aortic arch replacements (NAR)
      through a median sternotomy (n = 66). The early mortality rates for EAR and NAR
      were 5.6% and 16.7%, respectively (NS); the lower rate for EAR may be due to the
      fact that EAR were performed more recently than NAR. The differences between EAR
      and NAR with respect to the amount of blood transfused intraoperatively and the
      respiratory index at 12 hours after surgery were not statistically significant.
      In addition, the extracorporeal bypass time in EAR was no longer than that in
      NAR. Thus, as compared with the NAR procedure, the EAR procedure did not have a
      negative effect on early outcome. Regarding late results, the actuarial survival
      rates after EAR and NAR, respectively were 87% and 72% at 1 year, 87% and 69% at
      3 years (NS). The early thrombo-occlusion rates of the remaining false lumens
      after TAR in broad aortic dissections were 56% after EAR and 33% after NAR (p =
      0.21). These results suggest that EAR may be a more useful procedure in some
      patients requiring TAR.

PMID- 9170855
TI  - [Use of silicone stents for tracheobronchial stenosis due to tumors].
AB  - Six cases with tracheobronchial stenosis due to tumors were treated by Dumon
      stent (n = 3) or Dynamic stent (n = 3). Before placing the stent, the
      tracheobronchus was expanded by dilatation using a balloon or bougienage. The
      stents were placed successfully in all cases, and the symptoms of
      tracheobronchial stenosis disappeared. One case treated by Dumon stent and one
      case treated by Dynamic stent suffered from transient pneumonia after stent
      placement due to difficulty in sputum drainage, and one of these cases died of
      tracheal occlusion due to the sputum. In conclusion, for severe tracheobronchial
      stenosis due to tumors, dilatation by balloon or bougienage enables the stent to
      be placed more easily and safety. In cases with lowered capacity for sputum
      drainage, it is important to exercise care so as to ensure sufficient sputum
      drainage after placement of the stent.

PMID- 9170856
TI  - [Clinical study of a non-conduit repair for complete transposition of the great
      arteries with ventricular septal defect and pulmonary stenosis].
AB  - Between 1991 and 1996, we performed a new technique of non-conduit repair on five
      consecutive patients with complete transposition of the great arteries associated
      with ventricular septal defect and pulmonary outflow tract obstruction. There
      were no late deaths. This technique consisted of constructing an intraventricular
      tunnel with a patch that connected the left ventricle to the aorta, closing the
      pulmonary outflow tract, drawing the main pulmonary artery directly to the right
      ventriculotomy, and reconstructing the new right ventricular outflow tract with a
      monocusp patch. The main feature of this technique is the long acquisition of the
      main pulmonary artery by transecting it beneath the pulmonary valve. This
      technique enables direct anastomosis of the main pulmonary artery to the right
      ventricle through the natural route without dividing the aorta. In this point, it
      differs from Lecompte's maneuver which mobilizes the pulmonary arterial
      bifurcation in front of the ascending aorta. The postoperative clinical results
      were reviewed on 3 patients who underwent mid-term cardiac catheterization. The
      age at the operation was 5.8, 3.7, and 2.2 years old and the interval between the
      operation and the mid-term catheterization was 1.8, 3.0, and 2.1 years,
      respectively. The postoperative systolic pressure gradient across the right
      ventricular outflow tract was 4.20 mmHg (mean 10 mmHg) at the early stage and 8
      22 mmHg (mean 14 mmHg) at mid-term stage. The right ventriculogram at the mid
      term stage showed proportional growth of the right ventricular outflow tract in
      all patients. We conclude that this technique of non-conduit repair is the most
      desirable procedure for this type of anomaly.

PMID- 9170857
TI  - [Arterial-venous carbon dioxide tension difference after hypothermic
      cardiopulmonary bypass].
AB  - Arterial-venous carbon dioxide tension difference (Pv-aCO2) is known to become
      high after severe hemorrhage shock and resuscitation. We hypothesized that Pv
      aCO2 might be high after cardiac surgery because of the oxygen debt occurred
      during hypothermic cardiopulmonary bypass (CPB). Blood pressure, cardiac index,
      hemoglobin, the arterial and mixed venous blood gases were repeatedly measured
      every 6 hours for 24 hours following cardiac surgery in 60 adult patients who
      underwent hypothermic CPB. Immediately after the surgery, Pv-aCO2 was extremely
      high, then gradually decreased to within normal ranges 12 hours later (8.0 +/-
      2.9 mmHg vs 5.9 +/- 3.1 mmHg. p < 0.01). Factors which significantly correlated
      to Pv-aCO2 were cardiac index, oxygen delivery, minimum rectal temperature and
      duration of CPB. Oxygen debt during hypothermic CPB might cause significantly
      high Pv-aDO2. At least 12 hours were necessary to recover from anaerobic status
      to physiological condition.

PMID- 9170858
TI  - [Clinical experience with the gelatin-resorcine-formol biological glue in acute
      type A aortic dissection].
AB  - From May 1995 through June 1996, the gelatin-resorcine-formol (GRF) biological
      glue was used for tissue reinforcement in 20 patients operated on for acute type
      A aortic dissections at our institution. The results in these patients (Group I)
      were compared to those in 37 patients operated on between 1992 and 1994 with
      conventional techniques (Group II). There were no significant differences between
      the two groups concerning demographic data. Operative procedures in Group I
      consist of replacement of the ascending aorta with or without proximal arch (n =
      10), total arch replacement (n = 7), and aortic root reconstruction (n = 2),
      whereas those in Group II were 22, 12, and 3, respectively. Cardiopulmonary
      bypass time was significantly shorter in Group I than Group II (164 +/- 39 vs 265
      +/- 122, p < 0.05). Average blood loss in first 24 hours after operation was 688
      +/- 601 ml in Group I and 1481 +/- 1505 ml in Group II (p < 0.05). Consequently
      operative mortality was significantly (p < 0.05) reduced from 40.5% (Group II) to
      15.0% (Group I). In conclusion, the use of GRF glue reduces perioperative
      bleeding and improves results of operation for acute aortic dissections.

PMID- 9170859
TI  - [The effect of nitric oxide synthase inhibitor on reperfusion injury to the brain
      under hypothermic circulatory arrest].
AB  - The effect of nitric oxide synthase inhibitor-NG-nitro-L-argine methyl ester (L
      NAME)-on reperfusion injury of the brain under deep hypothermic circulatory
      arrest was experimentally investigated in sixteen piglets weighing about 30 kg.
      Cardiopulmonary bypass was established and animals were cooled to a brain
      temperature of 20 degrees C and circulatory arrest was performed for 60 minutes
      followed by reperfusion of 120 minutes. The value of nitric oxide (NO) within the
      brain was measured with a needle electrode which was inserted into the brain. In
      the treatment group L-NAME was administered with a intravenous injection of 1.5
      mg/kg at the beginning of the reperfusion followed by a 60-minute continuous
      venous infusion of 1.5 mg/kg/hour. In the control group the value of NO after 120
      minutes reperfusion increased significantly compared with pre-circulatory arrest,
      but in the treatment group it did not. There was significant difference between
      the groups regarding the NO value after 120 minutes reperfusion. Blood pressure
      after 120 minutes reperfusion in the treatment group was a little higher than the
      control group, but there was no significant difference between the groups
      regarding cerebral blood flow, excess lactate and cerebral tissue water content.
      However, recovery of SEP after 120 minutes reperfusion was detected in all 8
      cases of the treatment group, but only in one of the control group (p < 0.001).
      This data suggests that L-NAME protects the brain against the reperfusion injury
      under deep hypothermic circulatory arrest.

PMID- 9170860
TI  - [Open heart surgery without homologous blood transfusion for tetralogy of Fallot-
      use of hydroxyethyl starch diminishes the necessity of protein transfusion].
AB  - To avoid any blood or protein transfusions, we employed 6% hydroxyethyl starch in
      0.9% saline (saline HES) during cardiopulmonary bypass (CPB) for intracardiac
      repair in 24 consecutive patients with Tetralogy of Fallot (TF). The
      postoperative course has been satisfactory (central venous pressure 9.5 +/- 1.2
      cmH2O, duration of intubation after surgery 4.4 +/- 1.5 hours), and all patients
      but one did not require transfusion therapy during their hospital stay. We
      conclude that intracardiac repair without transfusions is feasible in almost all
      patients with TF, when substituting saline HES for blood or proteins.

PMID- 9170861
TI  - [An experimental study of a newly developed silicone coated membrane oxygenator].
AB  - The surface of polypropylene hollow fiber is successfully coated with very thin
      (0.2 micron) silicone layer. Using this fiber, membrane oxygenator was newly
      developed. To test its reliability biocompatibility and durability, experimental
      studies were performed using goats. Long-term (6 hours) normothermic
      cardiopulmonary bypass (CPB) model was applied in 10 animals. A conventional
      membrane oxygenator (Mera Excelung HPO-15H, MERA, Tokyo) was used in five goats
      as a control (C-NC group), and a new silicone coated membrane oxygenator, which
      is the exact same construction of C-NC group, in five (C-SC group). In the both
      groups, the same roller pump and circuit were used. The pump flow was 64.9 +/-
      5.1 ml/kg in C-NC group, and 65.7 +/- 3.1 ml/kg in C-SC group. There were no
      significant differences between the two groups Hemodynamics changes during
      pumping in the both groups were similar, and all animals could successfully wean
      from CPB. The O2 transfer and CO2 removal functions of C-SC group showed the same
      ranges as compared with that of C-NC group, indicating clinically acceptable
      values. In the parameters of coagulation, fibrinolytic and complement
      activations, there were almost no differences between the two groups. As for
      hemolysis, however, plasma free hemoglobin of C-SC group (56.2 +/- 43.9 mg/dl)
      was lower than that of C-NC group (125.7 +/- 65.3 mg/dl). In the scanning
      electron microscopy, much less platelet clots and red blood cell adhesion were
      observed in C-SC group as compared with C-NC group. Chronic (96 hours)
      percutaneous cardiopulmonary support (PCPS) model was applied in 6 animals. In
      this model, a same conventional membrane oxygenator was used in three goats as a
      control (P-NC group), and a new silicone coated membrane oxygenator, in three (P
      SC group). The O2 transfer and CO2 removal functions of the both groups showed
      the same ranges. Plasma free hemoglobin, the parameters of coagulation and
      fibrinolysis of P-SC group were lower than that of P-NC group, especially after
      72 hours support. In conclusion, this new oxygenator was reliable, biocompatible
      and durable, and it is suitable not only for CPB, but also for long-term cardiac
      support.

PMID- 9170862
TI  - [Prognosis and prognostic factor after extended lymphadenectomy in lung cancer].
AB  - From 1984 to 1994, 418 patients were received surgery for the lung cancer in our
      center. Of them, 178 patients were underwent extended lymphadenectomy. Fifty six
      of the 178 were histologically proven N2 of N3 alpha disease after surgery.
      Extended lymphadenectomy means R2b lymphadenectomy including the left
      tracheobronchial node dissection for the right lung cancer and R3 (bilateral
      mediastinal lymphadenectomy through a median sternotomy) for the left. In the 56
      patients, we examined the location and frequency of metastases to the mediastinal
      lymph nodes and the relationship between some clinical factors (pT, number of
      metastatic station, clinical staging of the lymph node (CN), histological type,
      contralateral mediastinal lymph nodes metastases) and prognosis. Most of the pN2
      patients of the right lung cancer showed ipsilateral mediastinal lymph nodes
      metastases and 25 percent of the patients showed the spread to N2b mediastinal
      modes. The patients of the left lung cancer showed higher incidence of
      contralateral mediastinal lymph nodes metastases than the patients of the right
      lung cancer. The five years survival rate of all pN2 patients (N = 39) was 48%,
      and T1 or T2-N2 patients (N = 22) was 67%. On the other hand, all T4 N2 patients
      (N-9) died within 3 years after operation. There was no significant difference in
      postoperative survival between the patients with single station metastasis (N =
      20) and multistation metastases (N = 30, including 11 cases with N3 alpha). The
      five years survival rate of all the patients with multistation metastases was
      45%, and that of T1 or T2 multilevel (N = 20) was 65%. There was significant
      difference in postoperative survival between the patients with CN0-pN2 and CN2
      pN2 (p < 0.05). The five years survival of CN0-pN2 patients (N = 14) was 85% and
      four years survival rate of CN2 pN2 patients (N = 19) was 30%. Among the patients
      with T1 or T2 tumor, however, there was no significant differences in
      postoperative survival between CN0-pN2 patients and CN2 pN2 patients. There was
      no difference in postoperative survival between adenocarcinoma and squamous cell
      carcinoma (5 years survival: 56%, 43%). In conclusion, extended lymphadenectomy
      has brought a good prognosis in the patient with T1 or T2 in spite of presence of
      CN2 or multistation N2. The patients with contralated mediastinal metastases (N3
      alpha) showed good prognosis after R3 (5 years survival: 100%) in the patients
      with the left lung cancer (N = 6). But the N3 alpha patients of right lung cancer
      showed poorer prognosis (3 years survival: 30%) after R3 (N = 5) than the left.
      It suggested that R3 lymphadenectomy was significant and beneficial for the left
      lung cancer patients with N3 alpha but controversial for the right.

PMID- 9170863
TI  - [Surgical outcomes of transverse aortic arch replacement].
AB  - The surgical outcomes of transverse aortic arch replacement were analyzed for the
      cases of 33 consecutive patients who underwent operations during the seven years
      between July 1989 and March 1996. Sixteen patients were atherosclerotic aneurysm
      (group T), 17 patients were acute or chronic aortic dissection involving aortic
      arch (group D). As for brain protection during aortic arch reconstruction,
      selective cerebral perfusion was employed in 16 patients of group T and 11
      patients of group D. In 6 patients of group D with acute type A aortic dissection
      or chronic type B dissection, deep hypothermic circulatory arrest at 18
      approximately 20 degrees C of rectal temperature was employed. In 14 patients of
      group T, selective cerebral perfusion was simultaneously started when we begun
      cardiopulmonary bypass. There were one operative death in group T patients
      (operative mortality 6.2%) and two in group D patients (operative mortality
      11.8%). Perioperative stroke was occurred in two patients of group T with
      complete recovery in one and with partial recovery in the other. The latter
      patient died of medistinitis and graft infection. There was no hospital death nor
      stroke in group D patients. Duration of selective cerebral perfusion was 157.8 +/
      54.4 minutes in group T patients, 140.1 +/- 66.5 minutes in group D patients (n
      = 11), duration of circulatory arrest was 49.5 +/- 11.4 minutes in 6 patients of
      group D patients, respectively. In 27 patients who underwent operation with
      selective cerebral perfusion, morbidity of stroke was 7.4% (two patients). These
      were caused by technical failure during arch vessel reconstruction and seemed to
      be avoidable. In conclusion, it is reasonable to employ selective cerebral
      perfusion for aortic arch reconstruction in atherosclerotic aneurysm of
      transverse aortic arch. In aortic dissection, either selective cerebral perfusion
      or deep hypothermic circulatory arrest is justified as cerebral protection during
      operation.

PMID- 9170864
TI  - [Surgical strategy for Stanford type A aortic dissection with Marfan syndrome].
AB  - Between January 1979 and May 1996, 23 Marfan patients underwent surgeries for
      type A aortic dissection; 8 patients with localized type dissection and 15 with
      extensive type. All of the 23 patients suffered from annuloaortic ectasia (AAE)
      which was treated by composite graft replacement, 10 of these patients had a
      concomitant replacement of the aortic arch. The operative mortality rate was
      8.7%, and the causes were associated with the methods of coronary artery
      reattachment to the graft. Of the 15 patients with the extensive type dissection,
      there were 11 patients who had a non-thrombotic communicating false lumen in the
      untreated segments of the distal dissected aorta after the first operation and
      from this group there were seven patients who had anastomotic leakage around the
      distal suture line of the graft replacement that was demonstrated by aortography.
      Extensive graft replacement ranging from the entire thoracic aorta to the total
      aorta were performed in 10 (43.5%). Late deaths occurred in three patients
      (13.0%) and these causes were LOS and graft infection after the second operation
      and prosthetic valve endcarditis 6 months after the first operation. The present
      data indicate that Stanford type A aortic dissection with Marfan syndrome should
      be undertaken on the basis of a prior achievable plan to perform an entire aortic
      replacement. The dissection should also be performed using a procedure which
      doesn't leave distal anastomotic leakage.

PMID- 9170865
TI  - [Surgical management of constrictive pericarditis].
AB  - Cases of constrictive pericarditis per a institute is few for decrease of this
      disease. Therefore for surgical management of constrictive pericarditis, it has
      not been clear whether cardiopulmonary bypass during operation is necessary or
      not, and the reports of long term results are few. We gathered information by
      questionnaires from thirty-four institutes, which constitute Tokai Cardiovascular
      Surgeons Conference in Shizuoka, Aichi, Mie and Gifu Prefecture, for surgical
      management of constrictive pericarditis, and investigated its results. Etiology
      of constrictive pericarditis is idiopathic (49%), tuberculosis (29%) or post open
      heart surgery (10%). Hospital death included operative death is 14%, and
      postoperative liver complications was many next to heart complications. The
      cases, whose NYHA functional class at discharge did not improve compared with
      preoperative state, was 33%. At one year after operation two third of them
      improved in NYHA functional class, but the others did not improved.

PMID- 9170866
TI  - [Treatment of thoracic esophageal carcinoma which invades adjacent structure-
      significance of resection and combined therapy].
AB  - From January 1980 to December 1994, a total of 64 cases of thoracic esophageal
      carcinoma which invaded adjacent structure (A3) were resected and 35 cases were
      unresected in Kagoshima University Hospital. Adjacent structures were mainly
      trachea/bronchus, aorta or pulmonary vein. Combined resections were performed in
      22 cases (34.4%), and no tumors remained in 12 cases (18.8%). One year survival
      rates and 50% survival time of the no residual tumor group were 25.7% and 8.5
      months, while the rates of the residual tumor group were 15.7% and 5.1 months.
      But, there was no significant difference of survival rates according to the
      amount of residual tumor. On the other hand, 1-year survival rates and 50%
      survival time of unresected group were 3.1% and 4.5 months. As a postoperative
      adjuvant therapy, radiation was the most effective modality. As a result,
      operations should be done at first for the A3 carcinoma in which a complete
      combined resection is expected. On the other hand, radiation or chemotherapy
      should be selected for the cases in which the tumor may remain, even though
      combined resection is done.

PMID- 9170867
TI  - [Effect of phosphate diester linkage of vitamin E and vitamin C (EPC-K1) on
      myocardial ischemia reperfusion injury in the isolated working rat heart].
AB  - The myocardial protective effect of phosphate diester linkage of vitamin E and
      vitamin C (EPC-K1), a new hydroxyl radical scavenger, was investigated in an
      isolated working rat heart model. Initially, 0.25-3.0 micrograms/ml of EPC-K1 was
      given to non-ischemic heart to examine the effect of EPC-K1. Cardiac function did
      not change until 3.0 micrograms/ml EPC-K1 administration, however percent change
      of aortic flow prior to treatment (%AF) decreased significantly with 3.0
      micrograms/ml and hearts were arrested with 5.0 micrograms/ml. Creatine kinase
      (CK) leakage did not change until 0.5 microgram/ml, however significantly
      increased over 1.0 microgram/ml. In the second protocol, EPC-K1 was applied
      before 15 min of ischemia at 37 degrees C. The %AF recovered significantly with
      0.5 and 1.0 microgram/ml (81.2 +/- 3.1% and 75.2 +/- 4.1% vs. 57.2 +/- 3.1% in
      the control group), but hearts did not start to beat with 2.0 micrograms/ml. CK
      leakage was suppressed with 0.5 microgram/ml, although not significantly. In the
      third protocol, 0.5 microgram/ml of EPC-K1, which had the best protective effect
      before ischemia, was administered during reperfusion after 15 min of ischemia at
      37 degrees C. The %AF (64.7 +/- 5.1%) was significantly higher than in the
      control group (57.2 +/- 3.1%), but was significantly less than in the pre
      ischemic EPC-K1 group (81.2 +/- 3.0%). Thus, EPC-K1 had a myocardial protective
      effect at an appropriate dose, especially when given before ischemia. However,
      EPC-K1 showed myocardial toxicity at a high dose, therefore use of the correct
      dose will be important.

PMID- 9170868
TI  - [Coronary artery bypass grafting in an octogenarian with chronic myelomonocytic
      leukemia].
AB  - Chronic myelomonocytic leukemia is a disease of the elderly. It tends to have a
      variable clinical course, as the patient's state is immunologically dysunctional.
      There has been reluctance to perform open cardiac procedures because of concern
      about early postoperative sepsis leading to death. A 84-year-old man was admitted
      for the management of effort angina. PTCA was performed twice. He had left
      nephrectomy for Grawitz tumor nine years ago and additionally, he had been
      diagnosed as having chronic myelomonocytic leukemia since the next year.
      Preoperative laboratory assessment revealed that the total white blood cell
      counts were 2500 with 25 per-cent of granulocytes, a hematocrit of 31.1%, and
      platelet counts were 10.0 x 10(4). At the night of the treatment of his
      granulocytopenia with injection of granulocyte stimulating factor, he complained
      of continuous anterior chest pain with ST depression on ECG. Emergency single
      CABG was performed using a saphenous vein graft under the diagnosis of impending
      myocardial infarction. Postoperative course was uneventful. This is the first
      case report of CABG in octogenarian with chronic myelomonocytic leukemia in the
      world.

PMID- 9170869
TI  - [A case report of surgical treatment for aneurysm of the brachiocephalic artery
      associated with tracheal stenosis].
AB  - A 76-year-old woman, diagnosed with aneurysm of the brachiocephalic artery
      thirteen years ago, encountered tracheostenosis due to tracheal compression
      induced by an increase in size of the aneurysm. Complete aneurysmectomy with
      graft replacement under cardiopulmonary bypass failed to improve the
      bronchostenosis. This was attributed to tracheomalacia developed as a result of
      malatic tracheal cartilages. On day 14 post operation, external fixation of the
      trachea with an autografted costa relieved her condition markedly. Aneurysm of
      the brachiocephalic artery is rare and asymptomatical. As such, the present case
      report suggests that patients with such a aneurysm should be promptly operated to
      present both the risk of arterial rupture and unfavorable compression of adjacent
      organs.

PMID- 9170870
TI  - [A simultaneous operation of aortic root, arch replacement, and sternal elevation
      for Marfan's syndrome--a case report].
AB  - A 42-year-old male was transferred to our institution by his family doctor
      because of suspected type A aortic dissection with cardiac tamponade. His
      physical constitution gave the appearance of Marfan's syndrome. Contrast CT
      revealed DeBaky type 1 aortic dissection. Angiography detected an Annulo-aortic
      ectasia complicated by an aortic regurgitation (AR) grade IV. He also suffered
      from a severe funnel chest. We performed simultaneous procedures of aortic root,
      arch replacement, and sternal elevation. Upon operation, a staged aortic clamp
      technique was employed to reduce the period of cardiac arrest. In the sternal
      elevation, the bilateral internal thoracic arteries were preserved. Post
      operative course was uneventful. We consider it effective to employ the staged
      aortic clamp technique in a reconstruction of the entire thoracic aorta in the
      case of poor cardiac function and to preserve the bilateral internal thoracic
      arteries in sternal elevation in order to prevent infection.

PMID- 9170871
TI  - [Surgical treatment of diffuse supravalvular aortic stenosis with Williams
      syndrome].
AB  - A five-year-old boy was admitted to our hospital because of a cardiac murmur and
      an abnormal electrocardiogram. He had a distinct pattern of facial features and
      mild mental and developmental retardation. An aortogram revealed that the aorta
      was hypoplastic from just above the Valsalva sinuses to the aortic arch.
      Moreover, the basal portions of the arch vessels were also hypoplastic. A
      diagnosis of diffuse supravalvular aortic stenosis was made. The pressure
      gradient between the left ventricle and the descending aorta was 74 mmHg on
      catheter examination. Surgical therapy was therefore indicated. The hypoplastic
      lesions of the aorta and arch vessels were enlarged with a Dacron patch under
      cardiopulmonary bypass and deep hypothermic circulatory arrest. The postoperative
      course was uneventful. The pressure gradient decreased to 7 mmHg on catheter
      examination. This type of supravalvular aortic stenosis is quite rare. Further
      follow-up is required to evaluate long-term outcome.

PMID- 9170872
TI  - [Surgical correction of an incomplete endocardial cushion defect in a 66-year-old
      male with the remarkable pulmonary hypertension].
AB  - A surgical case of a 66-year-old male with an endocardial cushion defect (ECD) is
      reported. He had preoperative pulmonary hypertension (80/25 mmHg, Pp/Ps 0.61),
      hypoxia (63.7 mmHg) and decreased creatinin clearance (45.7 ml/min). Respiratory
      condition was New York Heart Association's (NYHA's) grade III. Angiocardiography
      showed a typical gooseneck deformity associated with mitral and tricuspid valve
      regurgitations with the cleft (Seller's grade II and III). As surgical
      correction, direct suture of the cleft in an anterior leaflet with mitral
      annuloplasty, patch closure of the ostium primum defect with Xenomedical patch
      and tricuspid annuloplasty were performed. Postoperative data were restored to
      NYHA grade I. decreased pulmonary artery pressure (43/21 mmHg) and resistances
      (Pp/Ps 0.36). The only three surgical treatments of an incomplete ECD were
      reviewed in over 65-year-old patients in Japan included one perioperative death.
      Although we suggest it should be actively taken surgical repair even in elderly
      patients with pulmonary hypertension.

PMID- 9170873
TI  - [Blood cyst of the pulmonary valve in an adult--a case report].
AB  - Blood cysts of the heart valves are commonly reported at postmortem examination
      of infants but are rare seen in older children and adults. A 42-year-old woman
      was referred to our hospital for cardiac evaluation because of dyspnea on
      exertion and heart murmur. There was no history of cyanosis or cardiac failure.
      Cardiac catheterization revealed valvular pulmonary stenosis and atrial septal
      defect. Right ventricular angiography showed the circular filling defect 0.7 x
      0.7 cm in size at the suprapulmonary valve. However, this preoperative abnormal
      finding was diagnosed as a blood cyst after surgery. At operation a blood cyst
      originating from the right cusp of the pulmonary valve was found and resected,
      and was followed by commissurotomy of the pulmonary valve and direct closure of
      the atrial septal defect. Her postoperative course was uneventful.

PMID- 9170874
TI  - [Simultaneous surgical treatment for distal aortic arch aneurysm associated with
      innominate artery aneurysm and coronary artery disease].
AB  - The patient was 69-year-old male who admitted to our hospital in November 1995
      with the complaint of abnormal shadow on chest C-ray. CT scan and aortogram
      revealed aneurysms of the distal aortic arch and innominate artery. Seventy-five
      percent stenosis of the right coronary artery was also found in coronary
      angiogram. The total arch replacement and reconstruction of the innominate artery
      and CABG to right coronary artery were performed with the aid of cold blood
      cardioplegia and selective cerebral perfusion and open distal anastomosis.
      Ascending aorta was used for arterial cannulation to avoid the thromboembolism
      due to retrograde perfusion from the femoral artery. Satisfactory postoperative
      course was obtained except transient left hemiplegia and post operative three
      dimensional CT scan demonstrated the successful reconstruction. The patient was
      doing well 8 months postoperatively.

PMID- 9170875
TI  - [Traumatic transection of the descending thoracic aorta with free open rupture in
      left pleural cavity--a case report].
AB  - A 33-year-old male was admitted to our hospital because of mediastinal bleeding
      by the traffic accident. He was in shock state. Chest roentgenogram showed
      widening of the upper mediastium, massive pleural effusion and deviation trachea
      to right. Chest CT scan showed left hemothorax and deviated mediastinum to right.
      Immediately after the end of the CT scan, the pulse of bilateral femoral artery
      was not palpable. Therefore, we started cardiac massage and carried to the
      operation room in a hurry. Under cardiac massage, median sternotomy was made.
      But, there were no abnormal findings in the ascending aorta and arch. Under ECC,
      left anterolateral incision was added. We found that the transection of the
      descending thoracic aorta was transversely without preservation of the adventitia
      and it reached a round of the aorta. Five cm of the descending aorta from just
      distal to the left subclavian artery was replaced with 22 mm Hemashield graft
      under the separate perfusion of upper and lower body and circulatory arrest.
      Postoperative course was stable and the patient was healthy at present.

PMID- 9170876
TI  - [A case of Morgagni hernia composed of hypertrophic adipose tissue in the
      falciform ligament].
AB  - We report our recent experience with an asymptomatic case of Morgagni hernia
      composed of hypertrophic adipose tissue in the falciform ligament. The patient
      was a 47-year-old obese para-II woman. A chest X-ray during a routine health
      checkup showed an abnormal shadow in the right cardiophrenic angle that was
      larger than one year previously. Computed tomograms revealed a fat-density mass
      in the right side of the chest in contact with the anterior chest wall,
      pericardium and sternum that continued into the abdominal cavity. Magnetic
      resonance imaging (MRI) showed that the intrathoracic mass lesion was continuous
      with the subphrenic tissue, and that the hilus of the hernia was 5 x 3 cm in
      size. A barium gastro-intestinal series revealed no abnormal findings. Surgical
      repair was achieved through the transabdominal approach. The omentum was found in
      its normal position. The herniated adipose tissue in the falciform ligament was
      repositioned on the peritoneal side, and excised. The hilus of the hernia was
      then closed with knotted sutures. Postoperatively, the abnormal shadow on the X
      ray was no longer present, and the postoperative course was uneventful.
      Histological examination revealed the hernia to consist of mature adipose tissue
      5 x 10 x 3 cm in size. This is the first case of Morgagni hernia composed of
      hypertrophic adipose tissue in the falciform ligament reported in Japan.

PMID- 9170877
TI  - [A reconstruction of the left ventricle for post infarction left ventricular
      aneurysm complicated by ventricular septal perforation--a case report].
AB  - A 68-year-old male with post myocardial infarction left ventricular aneurysm
      (LVA) complicated by ventricular septal perforation (VSP) was treated surgically.
      At first, he was admitted with acute myocardial infarction by a physician.
      Coronary angiography (CAG) revealed a total occlusion of the left anterior
      descending coronary artery. It was improved to 99% of stenosis by PTCR. Echo
      cardiography revealed the VSP. However, the patient was approached conservatively
      because of complications of severe pneuminitis and acute hepatitis. Cardiac
      catheterization was performed three months after admission. The data on the
      catheterization are as follows: Left ventricular (LV) wall dyskinesis is
      presented at segment 1-5. Global ejection fraction (EF) = 26%, Corrected EF =
      40%, LVEDP = 36 mmHg, Qp/Qs = 1.8. Elective surgery was then performed with IABP,
      LVA was resected 90 x 50 mm in size under ventricular fibrillation. VSP, which
      was 9 mm in size, was closed directly with Teflon felt strips. LV plication was
      then made with 3.0 polypropylene under cardiac arrest. Reconstruction of the LV
      was then performed with a double patch, of which a cow pericardium was laid on
      top of a Gore-Tex patch. Post operative cardiac function was improved remarkably.
      We consider this procedure excellent because of the avoidance of thrombus and the
      maintenance of the LV form.

PMID- 9170878
TI  - [A case of bicuspid aortic valve stenosis with single coronary artery].
AB  - A 62-year-old female who had a complaint of palpitation was diagnosed as bicuspid
      aortic stenosis and left single coronary artery by the echocardiographic
      examination, cardiac catheterization study and coronary artery angiography.
      Aortic valve replacement was performed and the patient was discharged 22 days
      after surgery with good post-operative course. Preoperative coronary artery
      angiography was important in the case of aortic valvular disease.

PMID- 9170879
TI  - [The influence of anti-interferon-alpha 2a antibodies in initial daily four-week
      interferon-alpha 2a therapy for chronic hepatitis C].
AB  - Thirty-two patients with chronic active hepatitis C were initially treated with 9
      million units of interferon (IFN)-alpha 2a daily for 4 weeks and then thrice
      weekly for 20 weeks. The incidence of development and influence on clinical
      effectiveness of anti-IFN alpha 2a neutralizing antibodies measured by bioassay
      were investigated. Thirteen (41%) of the 32 patients developed antibodies, 4
      (12.5%) of whom exhibited a high titer of 128 NU or greater. There was a
      significant difference (p < 0.05) between responders and non-responders in the
      low viral load group (less than 10(5) copies/50 microliters) in the incidence of
      antibody development, with antibodies present in 2 of the 9 responders (22%) and
      5 of the 7 non-responders (71%). There was also a significant difference between
      the antibody-negative and antibody-positive patients in circulating HCV-RNA, 2
      5AS activity and average ALT levels at the latter half of treatment. In addition,
      2-5AS activity was significantly lower (p < 0.05) at completion of treatment in
      the high antibody titer group (128 NU or greater) than in the low antibody titer
      group. These results indicate that the development of anti-IFN neutralizing
      antibodies had a definite influence on the clinical course of IFN treatment for
      chronic hepatitis C.

PMID- 9170880
TI  - [Blood rheological study in rats with fatty liver--with special reference to
      effects of ethyl icosapentate].
AB  - A blood rheological study was conducted using Kikuchi's micro-channel method in
      rats with fatty liver. Effects of eicosapentaenoic acid (EPA) on blood rheology
      were also evaluated. Male SD rats given normal feed served as the control. One
      group was given choline-deficient feed for 4 weeks (EPA (-) group), while another
      group was daily given EPA (1000 mg/kg) for 4 weeks together with choline
      deficient feed (EPA (+) group). The micro-channel passage time was determined
      using 100 microliters of whole blood. The passage time significantly increased in
      the EPA (-) group compared to the control (p < 0.01). It significantly decreased
      in the EPA (+) group compared to the EPA (-) group (p < 0.01). Findings obtained
      in the present study suggested that blood rheological factors are related to the
      development of fatty liver and that EPA inhibits fatty changes of the liver by
      improving these rheological factors.

PMID- 9170881
TI  - [Two cases of gastric volvulus].

PMID- 9170882
TI  - [A case of G-CSF producing malignant fibrous histiocytoma of the small
      intestine].

PMID- 9170883
TI  - [A case report of von Meyenburg complex].

PMID- 9170884
TI  - [A case report of drug induced hepatitis and pancreatitis].

PMID- 9170885
TI  - [A case of congenital hepatic fibrosis successfully performed by esophageal
      transection for esophago-gastric varices].

PMID- 9170886
TI  - [A case of intrahepatic cholangiocellular carcinoma associated with primary
      biliary cirrhosis].

PMID- 9170887
TI  - [A case of biliobiliary fistula diagnosed by percutaneous transhepatic
      cholangioscopy].

PMID- 9170888
TI  - [A case of the aged man with acute onset autoimmune hepatitis].

PMID- 9170890
TI  - [A case of porcelain gallbladder with xanthogranulomatous cholecystitis
      masquerading as gallbladder cancer].

PMID- 9170889
TI  - [A case of multiple cholesterol polyps of the gallbladder with intermittent
      jaundice of frequent occurrence].

PMID- 9170891
TI  - Lipoprotein[a]: a predictor of atherosclerotic disease.
AB  - A unique construct of low-density lipoprotein (LDL), lipoprotein[a] has been
      shown to be a valuable independent risk factor for coronary artery disease. While
      not subject to dietary modulation, lipoprotein[a] nonetheless has provided one of
      the more promising leads to understanding genetic predisposition to arterial
      disease.

PMID- 9170892
TI  - Microorganisms as an alternative source of protein.
AB  - Demand for human food and animal feed proteins from nonconventional sources has
      increased, particularly in developing countries. Microbial protein is one such
      source. It is desirable because it is amenable to controlled intensive
      cultivation and is less dependent on variations in climate, weather, and soil.
      Microbial proteins must be evaluated for nutritive value, safety, and economic
      considerations before mass production is undertaken.

PMID- 9170893
TI  - Developing industrial-governmental-academic partnerships to address micronutrient
      malnutrition.
AB  - Micronutrient malnutrition affects approximately 2 billion people and has a
      significant impact on mortality, morbidity, reproductive health, individual
      growth and development, and economic productivity. The World Bank has suggested
      that micronutrient interventions are among the most cost-effective of all health
      interventions. Therefore, greatly increased collaborative efforts are needed to
      bring about further reductions in micronutrient malnutrition. At the FAO/WHO
      International Conference on Nutrition, the importance of various partners in
      improving nutrition was recognized in the World Declaration on Nutrition and
      adopted unanimously by 159 governments: "Governments, academic institutions and
      industry should support the development of fundamental and applied research
      directed towards improving the scientific and technological knowledge base" for
      addressing malnutrition, including micronutrient malnutrition. Food-based
      strategies, including fortification, provide a good example.

PMID- 9170894
TI  - Zinc lozenges reduce the duration of common cold symptoms.
AB  - A randomized, double-blind, placebo-controlled clinical trial has shown that
      treatment of the common cold with zinc gluconate lozenges resulted in a
      significant reduction in duration of symptoms of the cold. Patients received zinc
      containing lozenges or placebo lozenges every 2 hours for the duration of cold
      symptoms. The median time to complete resolution of cold symptoms was 4.4 days in
      the zinc group compared with 7.6 days in the placebo group. The mechanism of
      action of zinc in treating the common cold remains unknown.

PMID- 9170895
TI  - Neuropeptides responding to leptin.
AB  - Leptin, the circulating protein that inhibits food intake and energy expenditure,
      was thought to function through inhibition of the hypothalamic neuropeptide Y
      (NPY), a stimulator of food intake. However, mouse mutants lacking NPY are
      normal, suggesting that alternative neuromodulators of food intake must exist.
      Recently, melanocortin, a neuropeptide acting on the hypothalamic receptor
      melanocortin4-R, was discovered in mice, controlling energy regulation. This
      receptor is antagonized by the "agouti" protein in the mutant obese agouti mouse.

PMID- 9170896
TI  - [Why do you want to see?].

PMID- 9170899
TI  - [Visualized biomolecules as tools to explore cell function].

PMID- 9170900
TI  - [Organization and regulation of cells].

PMID- 9170901
TI  - [The site and the method for the viewing inside a living body].

PMID- 9170902
TI  - [Computer technology for bioimaging].

PMID- 9170903
TI  - [Software for image processing and its practical use].

PMID- 9170904
TI  - [3-D softwares and their practice].

PMID- 9170905
TI  - [Image technology and modern network system].

PMID- 9170906
TI  - [Drug design based on genome project and structural biology].

PMID- 9170907
TI  - [Molecular structure and function of proteins].

PMID- 9170908
TI  - [Getting the coordinates of proteins and displaying the spatial structures].

PMID- 9170909
TI  - [Inactivation mechanism of carboxymethylated RNase T1].

PMID- 9170910
TI  - [Three dimensional structure of the cytochrome c oxidase].

PMID- 9170911
TI  - [Three dimensional structure of CXC chemokines and its implication for the
      receptor recognition].

PMID- 9170912
TI  - [Conformational ensembles of biopolymers].

PMID- 9170913
TI  - [Structure and ligand recognition of pleckstrin homology domain].

PMID- 9170914
TI  - [Visualization of protein-DNA interactions].

PMID- 9170915
TI  - [3D-reconstruction of proteins by electron microscopy].

PMID- 9170916
TI  - [Computer simulations using molecular dynamics methods].

PMID- 9170917
TI  - [Structure and function of cells].

PMID- 9170918
TI  - [Optical microscopy].

PMID- 9170919
TI  - [Electron microscope].

PMID- 9170920
TI  - [Video microscopy].

PMID- 9170921
TI  - [Functional imaging of cells].

PMID- 9170923
TI  - [Molecular mechanisms of allergy].

PMID- 9170924
TI  - [Bioimages of cellular events].

PMID- 9170925
TI  - [Visualization of virus particles].

PMID- 9170926
TI  - [Visualization of protein molecules using fluorescence-labeled bioactive
      compounds].

PMID- 9170927
TI  - [Gaseous monoxides as an endogenous modulator of organ function--application of
      multifunctional digital microfluorography].

PMID- 9170928
TI  - [Mapping of cosmid clones by DNA fiber FISH].

PMID- 9170929
TI  - [Activation of neutrophil by cytokines].

PMID- 9170930
TI  - [Visual review: signal transduction in T cells].

PMID- 9170931
TI  - [Visualization of neural excitation].

PMID- 9170932
TI  - [Observation and RBC velocity measurement of microcirculation].

PMID- 9170933
TI  - [Functional morphology of harderian gland].

PMID- 9170935
TI  - [Tracer molecules and caged compounds].

PMID- 9170936
TI  - [Monoclonal antibodies].

PMID- 9170937
TI  - [Functional biosensor].

PMID- 9170939
TI  - [Scanning probe microscopy].

PMID- 9170940
TI  - [Tunneling microscopy].

PMID- 9170941
TI  - [X-ray microscope].

PMID- 9170942
TI  - [Two-photon excitation fluorescence microscopy].

PMID- 9170943
TI  - [Low light level imaging].

PMID- 9170944
TI  - [Imaging for realtime analysis system].

PMID- 9170945
TI  - [High speed and high precision multipoint photometric system].

PMID- 9170946
TI  - [Near-field optical microscopy using Evanescent-photons].

PMID- 9170947
TI  - [Optical tweezers: their principle and applications].

PMID- 9170948
TI  - [Detection systems of microorganisms].

PMID- 9170949
TI  - [Improvement of instruments].

PMID- 9170951
TI  - [Visualization of DNA-protein interaction and sliding motion of protein molecules
      along DNA].

PMID- 9170952
TI  - [Nuclear transport visualized by protein tagging systems including GFP].

PMID- 9170953
TI  - [A mechanism of mRNA transport in fission yeast: nucleolar involvement and heat
      shock inhibition in mRNA transport].

PMID- 9170954
TI  - [Analysis of the principal neutralization site of HIV-1 and vaccine research].

PMID- 9170955
TI  - [Imaging of intermolecular interactions: focused on actin-myosin interactions].

PMID- 9170956
TI  - [Visualized dynamics of microtubules and liposomes].

PMID- 9170957
TI  - [Observation of intracellular calcium kinetics with confocal laser scanning
      microscope].

PMID- 9170959
TI  - [Exocytotic hormone release].

PMID- 9170958
TI  - [Imaging of calcium signaling in brain glial cells and adrenocortical cells].

PMID- 9170960
TI  - [Structure and function of lytic granules].

PMID- 9170961
TI  - Introduction to the workshop on air pollution and health in the new Middle East.

PMID- 9170962
TI  - Short-term effects of air pollution on health: a European approach using
      epidemiologic time series data. The APHEA Project. Air Pollution Health Effects-
      A European Approach.

PMID- 9170964
TI  - Disparities in breast cancer screening: is it ethical?
AB  - Breast cancer incidence and mortality rise dramatically as women get older.
      Approximately 48% of newly diagnosed breast cancers occur in women 65 and over,
      while nearly 57% of the breast cancer deaths occur in these same women. A number
      of studies have found that elderly women are at increased risk for being
      diagnosed with advanced-stage breast cancer; nevertheless, it appears that
      elderly women do not have more poor prognostic factors that are associated with
      early relapse or short survival than younger women. Considering the fact that the
      population is aging and the increased incidence and mortality of breast cancer in
      the elderly, it is important to determine what can be done to reduce breast
      cancer mortality in the older segments of the population. Breast cancer screening
      with clinical breast exam and mammography, by leading to earlier diagnosis and
      therapy, improves the prognosis for survival. Nevertheless, data from the 1992 US
      National Health Interview Survey revealed that about 27% of women 65 and over had
      never even had a single mammogram. Of those who did have a mammogram, fewer than
      two-thirds had it within one year prior to the survey. The data for clinical
      breast exam were less discouraging, but nearly 20% of these women had never had
      an exam. From an ethical perspective, women in their mid-70s have an average of
      about 12 years of life remaining, and should be given every opportunity to live
      out these years in good health.

PMID- 9170966
TI  - WHO's strategy on standardization in laboratory pathology.

PMID- 9170965
TI  - Screening for thyroid abnormalities among immigrants to Israel from the former
      USSR.
AB  - The exposure of some former Soviet citizens to radiation following the 1986
      Chernobyl disaster has raised the question of the need to enroll these
      individuals in screening programs for thyroid abnormalities upon their
      immigration to Israel. Since screening programs have many drawbacks, and
      screening for thyroid disease has never been shown to decrease mortality or to
      improve survival, we are of the opinion that the establishment of thyroid
      screening programs will do more harm than good. The timely diagnosis of the very
      small excess in benign and malignant thyroid disease to be anticipated among the
      immigrants can be achieved in the community by the primary care physician armed
      with specific knowledge of the risks and the initial diagnostic approaches to
      suspected thyroid disease as well as information on the availability of
      specialist backup.

PMID- 9170967
TI  - [HIV infection and acquired immunodeficiency syndrome].
AB  - On June 4, 1981, MMWR published a report about Pneumocystis carinii pneumonia in
      homosexual men in Los Angeles. This was the first published report. A years
      later, this disease was named acquired immunodeficiency syndrome (AIDS). In the
      following year, Montangier et al in France discovered the causative agent, which
      they called lymphadenopathy virus (LAV), now known as human immunodeficiency
      virus (HIV). In 1985, solid-phase enzymeimmunoassay for the detection of the
      antibody to HIV was developed. Since then, other new techniques for the
      identification of HIV infection have been become available. These include more
      sensitive methods (for example; polymerase chain reaction techniques). Although
      these techniques facilitate early and definite diagnosis of infection, these
      tests may fail to detect the antibody in sera during window period of infection
      or overdiagnose infection in sera contaminated with genes not related to HIV.
      Although preventing blood exposure is the primary means of preventing
      occupationally acquired human immunodeficiency virus (HIV) infection, appropriate
      post-exposure management is an important element of workplace safety. Information
      suggesting that zidovudine (ZDV) postexposure prophylaxis (PEP) may reduce the
      risk for HIV transmission after occupational exposure to HIV infected blood
      prompted a Public Health Service (PHS) interagency working group, with expert
      consultation, and recommendations on PEP and management of occupational exposure
      to HIV in relation to these findings were discussed.

PMID- 9170968
TI  - [Prophylaxis of infectious intestinal diseases before leaving for underdeveloped
      countries].
AB  - Traveling to underdeveloped countries requires several important preventive
      measures, such as vaccination and bringing electric water boiling apparatus.
      After arriving in the underdeveloped country, travelers must avoid unheated
      water, ice, beverages containing ice, raw vegetables, fruits cut by local people.
      However, many Japanese travelers do not pay attention to these points, resulting
      in increasing numbers of cases of tropical diseases such as cholera, dysentery,
      giardiasis, among orally contracted intestinal diseases. We must learn from
      Americans and British who are very cautious in traveling to these areas. In
      addition to educating travelers about preventive measures, doctors who will see
      patients returning from traveling in underdeveloped countries must be able to
      recognize and treat tropical diseases. Unfortunately, this is often not the case
      in Japan, causing delays in diagnosis and treatment. It is imperative to diagnose
      communicable diseases as quickly as possible to avoid unnecessary secondary
      infections. Thus, for a traveler accumulating knowledge on the current hygienic
      conditions in the tropical country must also be one of the necessary
      preparations.

PMID- 9170969
TI  - [Infectious disease in Kenya--epidemiological study of diarrhoeal disease in
      children].
AB  - I participated in a project concerning diarrhea in children caused by bacteria
      (Japan International Cooperation Association) in the Republic of Kenya between
      April 1993 and March 1994. According to the Health Information Report by the
      Ministry of Health in 1993, diarrhea was at the 5th most frequent disease among
      outpatients and these patients numbered about eight hundred thousand. On
      microbiological examination, diarrhoegenic agents were detected from 767 of 1,362
      (56.3%) fecal specimens collected from children under five years of age with
      diarrhea. Major causative agents were diarrhogenic Escherichia coli (DgEC), Rota
      virus, Shigella spp., Entamoeba histolytica, Salmonella spp., and Giardia
      lamblia, which were detected from 17.2%, 11.4%, 6.3%, 5.8%, 5.4% and 3.6%,
      respectively. The results suggested that diarrhea was caused by drinking water
      with fecal contamination. We bacteriologically examined drinking water in the
      patients' houses, and many Enterobacteriaceae were detected in most of the
      specimens.

PMID- 9170970
TI  - [The data processing of neurophysiological examination and the diagnostic support
      system].
AB  - Neurophysiological examinations include EEG, EMG, Evoked Potential (EP) and ENG.
      In this paper, EEG and EP data processing, and the diagnostic support system
      using these findings were discussed. The FFT and AR model for analysis of
      frequency, and the pattern recognition for spike or spindle detection are the
      technical methods for application to EEG data processing of the first order.
      Amplitude or phase mapping techniques, as a second order data processing, were
      not only applied to the diagnosis of neurological disorders, but also used for
      detection of electrical equivalent dipole source localization which was inversely
      reconstructed in the cerebral cortex from the distribution of EEG potentials on
      the scalp. The averaging technique was used for detection of small evoked
      potentials (EP) such as SEP or ABR. The following items were included in the
      diagnostic support system applied to data processing. 1) Topographic analysis in
      the brain mapping of SEP to median nerve stimulation was applied to the
      identification of the central sulcus during a neurosurgical procedure to maintain
      the QOL of patient. 2) The usefulness of EEG automatic reporting system with
      Japanese sentences and brain topographic mapping was described. 3) Digital EEG in
      a data filing system using magneto optical disks was used for data analysis and
      diagnostic support system after EEG examination.

PMID- 9170971
TI  - [Medical practice-supporting system in pulmonary function testing].
AB  - A pulmonary function testing system which automates measurement, storage and
      reporting as much possible has been functioning in Mitsui Memorial Hospital since
      1992. Data obtained from four measurement apparatus are transferred to the
      central microcomputer by a local area network (LAN). To facilitate automatic
      interpretation, we developed a knowledge-based system using 87 production rules
      called 'PADRES', because the knowledge-based system had the following advantages
      over other systems; (1) The expression of knowledge is understandable and new
      pieces of knowledge can be easily added, (2) the process of reasoning can be
      clearly shown, and (3) the accumulation of many instances of data is not
      required. Using 'PADRES', it takes 2.6 seconds to interpret one set of data on
      average. Our system performs about 5,000 routine pulmonary function tests per
      year without faults. Because the program for interpretation is a separate module
      written in C language, it is readily portable to other operating systems (OS),
      although its original target was OS-9, a multitask operating system for
      microcomputers. In conclusion, the application of a knowledge-based system for
      microcomputers in the pulmonary function test laboratory was considered
      successful.

PMID- 9170972
TI  - [Record and preservation of ultrasound images and computer-assistant analysis-
      estimation of digital filing system and texture analysis].
AB  - Digital filing systems have advanced with computer technology and are among the
      most interesting modalities for recording and preserving ultrasound images. The
      benefits are reduced expense, superior imaging, and ease in searching previous
      records compared with those factors in conventional constant film, videotape, and
      other storage systems. Computer-assisted analysis of digital images for automatic
      differentiation of diseases has recently been studied. Conventional quantitative
      estimation methods of tissue characterization or histogram are not easy to apply
      to clinical studies because these methods are time-consuming, and require a
      specialized machine for this propose. We propose a new method of texture analysis
      of echo images. This new method depends on the echo-texture of the organ, and can
      clearly differentiate liver cirrhosis from normal liver. These new digital
      techniques for clinical studies may facilitate examination.

PMID- 9170973
TI  - [Digital filing system for medical image data].
AB  - To establish practical, effective medical digital image filing systems, various
      problems remain to be solved. The authors focused on 2 such problems of great
      importance: image data compression and standard specifications for digital data
      storage. From a variety of image compression algorithms now available, 2D-Color
      Doppler image compression was clinically investigated using the Joint
      Photographic Expert Group (JPEG) method. In low grade compression, the images
      decompressed showed no significant alterations in image quality, however, in
      higher grades of compression attained through irreversible coding in the JPEG
      method, the images showed subtle but significant alterations: emergence of 2
      kinds of artifact, i.e., borderline-artifact produced in the DCT procedures and
      pseudo color spots. The reproducibility of colors was found to be altered by
      changing the quantization table in the JPEG procedure. It was thought necessary
      to choose a proper quantization table and examine the DC coefficients (number of
      pixels) in the DCT procedure to attain practical 2D-Color Doppler image
      compression by the JPEG method. Although attempts in Japan are being made to
      establish common standards for electronic data storage, based on MEDIS, in an
      effort to promote standardization there are many problems to be solved before
      practical use is possible. To ensure common availability as required by the
      technical standards, it is necessary to organize minimum-required specifications
      into common standards and make them open to the public.

PMID- 9170974
TI  - [Definition and morphological features of apoptosis].
AB  - The term apoptosis, an ancient Greek word used to describe the "falling off" of
      petals from flowers or leaves from trees, was proposed by Kerr, Wyllie and Currie
      in 1972 to refer to the peculiar morphology of physiologically occurring cell
      death which plays a complementary but opposite role to mitosis in the regulation
      of animal cell populations. Apoptosis is opposed to necrosis-the appearance of
      accidental and pathological cell death. Apoptosis involves loss of microvilli,
      smooth-surfaced protuberances, chromatin condensation, nuclear and cytoplasmic
      condensation, loss of cell volume, and nuclear fragmentation. At an early stage,
      condensed chromatin tends to marginate in crescents around the nuclear envelope
      in most cell types, but in certain cells such as thymocytes, it often occupies
      much of the nuclear volume. Contrasted to necrosis, in apoptotic cells there are
      neither swelling and rupture of cytoplasmic organelles and plasma membranes nor
      inflammatory reaction. Apoptotic cells break up into membrane bound apoptotic
      bodies and they are phagocytosed by nearly resident tissue cells. These
      morphological changes are often accompanied by the internucleosomal DNA
      fragmentation. Apoptosis is a representative morphology of programmed cell death
      (PCD) which occurs within a developmental context in response to a definable
      physiological stimulus and requires de novo gene expression. However, apoptosis
      should not be considered synonymous with PCD. Because, there are examples of non
      apoptotic PCD and pathological stimuli such as mild cell injury can induce
      apoptosis.

PMID- 9170975
TI  - [Molecular biology of apoptosis].
AB  - Apoptosis, a mechanism involving programmed cell death, is important for normal
      development and maintenance of tissue homeostasis of multicellular organisms.
      Apoptotic cells are defined by their fragmented nuclei with condensed chromatin,
      fragmented or condensed cytoplasm and formation of apoptotic bodies. The
      apoptotic signal transducing pathways activated by a variety of stimuli,
      including depletion of growth factors, heat shock, cytokines, DNA damaging
      reagents and crosslinking of Fas receptor, finally converge into the
      phylogenically conserved apoptotic main machinery, consisting of death-driving
      ICE-family proteases and anti-cell death protein Bcl-2. Recently, we noted that
      necrotic cell death induced by chemical hypoxia shares at least some part of the
      apoptotic main machinery. Using this system, we have shown that Bcl-2 prevents
      the loss of the mitochondrial membrane potential observed in both apoptotic and
      necrotic cell death. We also showed that the ICE protease cascade operates in
      apoptosis and that Bcl-2 functions upstream of the ICE prolease cascade. Here, we
      review the signal transducing pathway of the apoptotic main machinery.

PMID- 9170976
TI  - [Apoptosis in human diseases: role of Fas system in liver cell injury by viral
      hepatitis].
AB  - Hepatitis C virus (HCV) and hepatitis B virus (HBV) are major causative agents of
      chronic liver disease. However, the mechanisms responsible for liver cell injury
      remain to be clarified. Cytotoxic T lymphocytes play a crucial role in liver cell
      injury by HCV or HBV infection. Recently, perforin and Fas ligand have been shown
      to be the only molecules causing T cell-mediated cytotoxicity in short term
      assays. Therefore, we examined the implication of the Fas system-mediated
      apoptosis in the liver cell injury. When examined by immunohistochemical method,
      Fas antigen expression in chronic hepatitis C or B was upregulated in accordance
      with the severity of liver inflammation. Furthermore, Fas ligand expression was
      detected in liver-infiltrating mononuclear cells obtained from patients with
      chronic hepatitis C. These observations suggest that the Fas system plays a
      dominant role in liver cell injury by viral hepatitis.

PMID- 9170977
TI  - [Immunohistochemical study of thymidine phosphorylase in uterine cervical
      intraepithelial neoplasia].
AB  - Studies have shown that thymidine phosphorylase (TdRPase) activity in various
      tumors is higher than that in normal tissues. We studied the immunohistochemical
      localization of TdRPase in uterine cervical intraepithelial neoplasia (CIN) using
      monoclonal antibody against TdRPase. Sixty-nine patients were studied: CIN 1, 14;
      CIN 2, 15; CIN 3 (severe dysplasia), 23; CIN 3 (carcinoma in situ), 17.
      Immunoreactivity for TdRPase was found in 29% of CIN 1, 40% of CIN 2, 70% of CIN
      3 (severe dysplasia), and 88% of CIN 3 (carcinoma in situ), showing increasing
      incidence with the progression of tumor grade. Furthermore, in higher grade
      tumor, more immunoreactive cells were found with increased intensity of
      immunoreaction. Both nucleus and cytoplasm of atypical cells showed
      immunoreactivity in most TdRPase positive cases, while either nucleus or
      cytoplasm was positive in a few cases. The stromal tissues were negative for the
      antibody except 3 cases of CIN 3 (carcinoma in situ) in which the stromal tissues
      adjacent to the tumor was positive. Our data suggest that immunoreactivity of
      TdRPase in CIN may correlate with the grade of CIN.

PMID- 9170978
TI  - [Seasonal changes of laboratory data in patients with Japanese cedar pollinosis].
AB  - Japanese cedar pollen (JCP) causes a significant seasonal allergic rhinitis in
      Japan during the early spring. Blood samples were collected monthly from October
      1993 through October 1994 from 11 patients with Japanese cedar pollinosis. The
      patients were segregated into two categories based on specific IgE (RAST): single
      positive RAST to JCP only and multiple positive RAST to JCP, house dust (H1) and
      mite (D1). These two populations differed in levels of total serum IgE, numbers
      of eosinophils, basophils and neutrophils in peripheral blood and clinical
      symptoms. Seasonal increase of JCP-specific IgE was observed after pollen season
      in both groups. In the single positive group, but not in the multiple positive
      group, seasonal increase of the number of eosinophils in peripheral blood was
      observed with post seasonal fall and the level of total serum IgE was increased
      in the same manner as that of the JCP specific IgE. Although it was not
      significant, there was a broad seasonal increase of serum nitrate anion, a
      metabolite of nitric oxide.

PMID- 9170979
TI  - [Plasma macrophage colony-stimulating factor, granulocyte macrophage colony
      stimulating factor and granulocyte colony-stimulating factor levels in continuous
      ambulatory peritoneal dialysis patients].
AB  - From a pathophysiological perspective, several studies have been performed on
      cytokines in chronic renal failure patients treated with continuous ambulatory
      peritoneal dialysis (CAPD). Because the peritoneal macrophages in CAPD patients
      produce some cytokines and the urinary secretion route for cytokines lost in
      those patients, CAPD patients are considered to have different plasma cytokine
      levels. Among the various cytokines, research on certain inflammatory cytokine
      levels has been reported. In studies of CAPD patients, peripheral blood and
      dialysate can be used as specimens. There are two methods of research. One
      involves determining the cytokine concentration in specimens and culture
      supernatant, while the other is to determine the mRNA expression of mononuclear
      cells in specimens and cultured mononuclear cells. The plasma levels of
      macrophage colony stimulating factor (M-CSF), granulocyte macrophage colony
      stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF)
      were measured in CAPD patients without peritonitis. Plasma M CSF, GM CSF and G
      CSF levels in CAPD patients were higher than those in healthy volunteers (p <
      0.0001).

PMID- 9170980
TI  - [A case of red blood cell(RBC) agglutination on peripheral blood smear and effect
      of cefpirom sulfate].
AB  - We observed red blood cell (RBC) agglutination on peripheral blood smear and an
      abnormal RBC distribution histogram that suggested the influence of cefpirom
      sulfate. The patient was receiving cefpirom sulfate when RBC agglutination and
      the abnormal pattern were recognized, but these abnormalities disappeared as soon
      as the drug was withdrawn. When the peripheral blood sample was re-examined after
      warming for an hour at 37 degrees C, the abnormal pattern almost disappeared and
      RBC agglutination became minimal. We also observed cold agglutination reaction by
      using O type washed RBCs from a healthy individual that were reacted with
      cefpirom sulfate, but found only minimal agglutination at RT. As the drug
      concentration and plasma concentration were increased, we observed more
      agglutination at 4 degrees C, but this agglutination disappeared after incubation
      for an hour at 37 degrees C. The cold agglutinin titer was normal. We thus
      believe that the cause of RBC agglutination in this case was caused by cefpirom
      sulfate.

PMID- 9170981
TI  - [Developing the portable type sleep apnea detector, and verifying the usefulness
      of the device].
AB  - Polysomnographic recording is indispensable in the diagnosis of sleep apnea
      syndrome (SAS). However, this method has a number of drawbacks, for example,
      subjects cannot sleep naturally like at their homes, and the methodology involved
      is complicated. We have now developed Portable Type Sleep Apnea Detector (PSD)
      that needs to equipment to provide subject's body. This study was done to verify
      the usefulness of this device. Subjects were 50 patients (42 male and 8 female,
      average and S.D. of age: 47.0 +/- 14.5), who were suspected to have SAS.
      Polysomnography and sleep recording using PSD were performed simultaneously. PSD
      consisted of three sensors for respiratory movements, a sensor for breathing
      sounds and a data recorder. The recorder was an 8K32 type 4-channel Handycorder
      (Nippon Denki Sanei, 370 mm x 115 mm x 200 mm, 7.5 kg) and the sensor for
      respiratory movements was a thin plate (180 mm x 100 mm). The three sensors for
      respiratory movements were placed between the mattress and bedsheet, hence the
      subjects did not feel them during sleep. A sound sensor detected breathing sounds
      such as snoring. We defined whether a subject is in sleep or awake by the number
      of body movements recorded by this device. Apnea was defined as depressed or
      stopped respiratory movement with no snoring for a period longer than 10 seconds.
      Standard polysomnography which consisted of electroencephalogram (2 channels),
      electrooculogram (2 channels), electromyogram (2 channels), electrocardiogram (1
      channel), oral (1 channel) and nasal airflow (1 channel) and chest movements (1
      channel) were performed. Sleep stages were evaluated according to the standard
      methods. The apnea hypopnea index (AHI) was defined as the number of apneas and
      hypopneas per sleep-hour. Significant correlation between each type of sleep
      apneas, AI and AHI as measured by two methods, was found (obstructive type: r =
      0.929; p < 0.001, central type: r = 0.880; p < 0.001, mixed type: r = 0.952; p <
      0.001, AI and AHI: r = 0.956; p < 0.001). It was concluded that this device is
      useful for screening SAS.

PMID- 9170982
TI  - [Clinical study of severe anorexia nervosa: the role of intravenous
      hyperalimentation therapy].
AB  - In order to understand the psychopathology of severe anorexia nervosa (AN), and
      determine appropriate therapeutic approaches, a clinical study was conducted on
      13 patients with severe AN who were hospitalized and were treated with
      intravenous hyperalimentation (IVH). The patients were divided into three types
      based on their clinical symptoms and initiating factors: Type I (Restricting
      Type; "Non-dieters"), Type II (Restricting Type: "Dieters"). Type III (Binge
      eating/Purging Type). The clinical features of each type were evaluated. Based on
      this evaluation, the basic approach and the role of IVH in the treatment of each
      type are described as follows. Type I: The patients experience loss of appetite
      and subsequently, suffer involuntary weight loss as a result of psychological or
      physical stresses at school and/or home. Since the patients do not intentionally
      restrict food intake, they cannot explain the loss of appetite. The age at onset
      of this type is the youngest among the three groups. The patients are
      introverted, passive and not good at expressing their emotions. Therefore, it is
      often difficult to deepen the emotional commitment further. It is possible to
      understand the pathology of Type I through the psychosomatic model. IVH therapy
      promotes benign regression for Type I patients, so that the mother-child
      relationship may be restored. As the therapeutic progress, the mother child
      relationship occasionally become ambivalent. In such a case, it is important for
      the treatment team to support independent activities of the patients. Type II:
      The patients lose weight by intentionally restricting necessary food intake for
      reasons such as beauty or sports. Any experience of failure in studies or sports
      or trouble in complex personal relations can trigger the onset of AN. Weight loss
      is looked as a great achievement, whereas weight gain is recognized as a serious
      failure of self-control. Since type II patients understand the necessity of
      receiving treatment, it is possible to establish a trusting relationship during
      therapy. Their prognosis is generally good. The psychotherapeutic approach for
      Type II patients is most effective in the context of a weight gain program
      utilizing behavior therapy. It is important for the therapist to integrate
      psychological approach with physiological approach using IVH, and to modify
      cognitive distortion and body image disturbance. Type III: The patients have
      regularly engaged in binge eating or purging (or both) in the progress of AN. But
      as they intensely fear becoming fat, they refuse to maintain a minimally normal
      body weight. Therefore, they exhibit recurrently inappropriate compensatory
      behavior in order to prevent weight gain. In the therapeutic sessions, they often
      become ambivalent and unstable, showing dissatisfaction and reacting strongly
      against their therapists. The age at onset is the oldest of the three types. The
      prognosis is not good in many cases. IVH therapy may be required only in life
      threatening situation for Type III patients. And severe bulimic patients may
      require sufficient drug treatment. The patients should be trained for
      interpersonal relationships at the day care unit or the occupational therapy
      unit. And they should be encouraged to adapt to real life.

PMID- 9170983
TI  - [Psychiatric effects of the great Hanshin earthquake (1995): from the psychiatric
      outpatient department of a general hospital close to the disaster-stricken area].

PMID- 9170984
TI  - Understanding Medicare managed care.

PMID- 9170985
TI  - Constitution and Bylaws amendments.

PMID- 9170986
TI  - [Material of the 7th Russian Congress of Radiologists. Vladimir, 24-27 September
      1996. Abstracts].

PMID- 9170987
TI  - Old wives' tales about pregnancy and childbirth.

PMID- 9170988
TI  - Violation in caring for the physically disabled.
AB  - Based on in-depth interviews, this article reports how people with disabilities
      perceive and experience the care given by public health care personnel. A major
      and disturbing finding is that the informants describe feelings of being
      violated, transgressed, and infringed upon by the personnel in change of their
      care. Because of the way nurses and other health care personnel interact,
      patients' bodies are often perceived as objects. The article describes some of
      these feelings, including how the informants construct different body boundaries
      in order to handle the violation of their body and body zone, and it discusses
      some features of the health care professions that may cause the informants'
      feelings of being violated.

PMID- 9170989
TI  - Social support and network conflict in firefighters and paramedics.
AB  - The relationship(s) between self-rated social support network conflict (both at
      work and off-work) and self-report measures of occupational stressors, job
      satisfaction, and health outcomes were examined in samples of currently employed
      professional firefighters (n = 1,730) and paramedics (n = 253). In both samples,
      perceived social support and network conflict at work were more strongly
      correlated with job satisfaction and work morale, as well as a measure of their
      appraised occupational stressors, than with their comparable home (off-work)
      satisfaction/conflict ratings. The path analysis generated suggested that, with
      only one exception, social support and relational conflict in the combined
      respondent sample could be conceptualized as direct sources of stress influencing
      the respondents' appraisal of their occupational stressors. The path model
      further suggested that firefighter/paramedics' appraisal of their occupational
      stressors mediated the network variables' influences on self-reported job
      dissatisfaction and stress symptom health outcome measures.

PMID- 9170990
TI  - Recruitment and retention of families in clinical trials with longitudinal
      designs.
AB  - The Family Home Visitation Program: Nurse as Coach was a 3-year, National Cancer
      Institute-funded, multisite, randomized trial of a nursing intervention. It
      tested the effectiveness of an in-home coaching intervention designed to enhance
      long-term adjustment of breast cancer's effect on family functioning. We
      summarize our recruitment and retention experiences, review accrual and retention
      issues identified from our experiences and those of other researchers, and
      suggest 24 specific strategies to maximize sample size in future clinical trial
      studies. Our target sample consisted of 200 women with early stage breast cancer
      and their male partners and children. We obtained 313 eligible referrals from 91
      sites: 217 participants (69.3%) were accrued, 96 families (30.7%) refused, 181
      participants (83.4%) were retained, 11 (5.1%) were dropped because of changes in
      eligibility status or because of scheduling error, and another 25 (11.5%) elected
      to withdraw.

PMID- 9170991
TI  - Quality of life in women with ovarian cancer.
AB  - Despite growing interest in quality of life (QOL) as an important variable in
      nursing and health care, little research focuses on QOL in women with ovarian
      cancer (OVCA). The purpose of this study was to examine QOL in OVCA survivors.
      The convenience sample consisted of 152 women in all disease stages. Quantitative
      data were collected using the QOL-Cancer Survivors tool and a demographic sheet.
      Qualitative data were collected by asking participants to write their definitions
      and experiences of QOL since their diagnosis. Reliability and validity of all
      data and findings were established. Findings reveal that QOL is moderately high
      for this group of cancer survivors, despite some specific negative facets of the
      illness and treatment experience. Qualitative analysis elaborates the four
      domains of Ferrell's QOL model: physical, psychological, social, and spiritual
      well-being. Qualitative data also reflect the complexity of the cancer
      experience.

PMID- 9170992
TI  - Spiritual interventions provided by mental health nurses.
AB  - This descriptive qualitative study explored the spiritual nursing interventions
      provided by mental health nurses. Fifty mental health nurses responded to open
      ended interrogative statements to report on nursing interventions in three
      situations that supported the spiritual needs of patients and families. Their
      responses were grouped into four categories, nurses being with the client, doing
      for the client, encouraging the client to look inward, and encouraging the client
      to look outward. Being with was demonstrated through the presence of the nurse.
      Doing for included interventions performed on the client's behalf and included
      the nurses using time, people, and space to provide care. Clients were encouraged
      to look inward for strength and look outward for people and objects that could be
      resources for them. A serendipitous findings was that mental health nurses were
      able to describe the ideal spiritual interventions but reported fewer instances
      of actually having intervened.

PMID- 9170993
TI  - A triangulation approach to testing a family instrument.
AB  - Sequential triangulation was used to test the validity of the Assessment of
      Strategies in Families (ASF), a screening tool for family effectiveness, and its
      application to families experiencing chronic pain. First, 30 subjects with
      chronic pain completed the questionnaire. Next, for the purpose of item
      validation, the subjects explained their thought process for each choice on the
      questionnaire. Results showed that they interpreted the items as intended.
      Subjects then responded to a semistructured interview about their perception
      about family stability and growth patterns. Thematic analysis suggested a
      tendency toward isolation from the community, intense involvement in each other's
      lives, and rigid control of family operations. ASF results reflected the trends
      by a low family-growth subscore, and a high or low stability score, depending on
      the success in achieving cooperation of family members. The findings suggest the
      instrument is valid and appropriate to screen families with chronic pain.

PMID- 9170994
TI  - Three phases of research in validating nursing diagnoses.
AB  - The purposes of this three-phase project consisting of concept analyses, nurse
      expert validation, and client validation were: identification of nursing
      definitions of anxiety and fear, validation of defining characteristics of the
      diagnoses by nurse experts, differentiation of the diagnoses by nurse experts,
      and validation of the nursing diagnosis anxiety by clients. The nurse expert
      sample consisted of 233 professional nurses, and the client sample consisted of
      69 adult clients. Results include agreement on two critical defining
      characteristics of anxiety by nurse experts and clients, the differentiation of
      anxiety and fear by nurse experts, the suggestion of a fear-anxiety syndrome in
      the literature and by nurse experts and clients, and the suggestion by nurse
      experts that anxiety be defined using levels of anxiety. Recommendation for
      changes in the nursing diagnosis anxiety are discussed.

PMID- 9170995
TI  - Unanticipated results of continuity of care research with the elderly--Part 1:
      Design issues.

PMID- 9170996
TI  - Thermal expansion coefficient of dental composites measured with strain gauges.
AB  - OBJECTIVES: A simple test method was developed to determine the coefficient of
      thermal expansion of prevailing restorative resin composites and to study the
      transient behavior as a function of temperature and repeated thermocycles.
      METHODS: Strain gauges were used to determine the thermal expansion for seven
      commonly used restorative resin composites by measuring the instantaneous strain
      along with temperature change. The temperature was measured by means of a
      thermocouple, the tip of which was embedded in the composite. The differences
      among the test groups were analyzed using ANOVA, followed by Scheffe's multiple
      comparisons test. RESULTS: The coefficient of thermal expansion determined for
      the composites tested was: 22.5 +/- 1.4 x 10(-6)/degree C (Z-100), 23.5 +/- 1.4 x
      10(-6)/degree C (P-50), 32.6 +/- 1.6 x 10(-6)/degree C (Herculite XR), 34.1 +/-
      1.8 x 10(-6)/degree C (APH), 35.4 +/- 1.4 x 10(-6)/degree C (Conquest), 41.6 +/-
      1.5 x 10(-6)/degree C (Silux Plus), 44.7 +/- 1.2 x 10(-6)/degree C (Heliomolar).
      The coefficient was almost linear in the considered temperature range (26-75
      degrees C) for all composites (r > 0.99) and decreased with each consecutive
      thermocycle (p < 0.1). SIGNIFICANCE: Thermally induced loads, introduced into
      restored teeth by the mismatch of the coefficient of thermal expansion of the
      tooth and the restorative material, may be related to microleakage and wear
      problems. A highly filled hybrid composite such as Z-100 had a coefficient of
      thermal expansion closest to that of the tooth crown, confirming other studies
      which demonstrated the benefits of high filler loading in matching the properties
      of the dental hard tissues.

PMID- 9170997
TI  - Improved properties of amorphous calcium phosphate fillers in remineralizing
      resin composites.
AB  - OBJECTIVES: The rationale for this study was based on the hypothesis that the
      mechanical strength of methacrylate composites containing the bioactive filler,
      amorphous calcium phosphate, can be enhanced by synthesizing this filler in the
      presence of glass-forming agents. Specifically, this study was conducted to
      prepare composites with zirconia- and silica-modified amorphous calcium phosphate
      fillers, and to determine whether the remineralization potential from the release
      of calcium and phosphate ions and the mechanical properties of the corresponding
      methacrylate composites were enhanced. METHODS: The modified amorphous calcium
      phosphates were synthesized at pH 10.5 by mixing 800 mmol/L Ca(NO3)2 solutions
      and either 250 mmol/L zirconylchloride (ZrOCl2) or 4.4 mol/L tetraethoxysilane
      (TEOS) solutions with solutions containing 525 mmol/L Na2HPO4 and 11 mmol/L
      Na4P2O7. After washing and drying, the amorphous calcium phosphates were mixed
      with visible light-activated resins and photopolymerized to form composite disks
      that were then examined for their ability to release Ca2+ and total ionic
      phosphate (PO4(3-) + HPO4(2-) + H2PO4-, hereafter indicated as PO4) by immersion
      in HEPES-buffered (pH 7.4) saline at 37 degrees C. Solution ion concentrations
      were compared at regular intervals up to 265 h. Biaxial flexural strengths of the
      composites before and after immersion were compared, and significant differences
      were established by Student's test (p < 0.05). RESULTS: Both ZrOCl2- and TEOS
      modified amorphous calcium phosphate composite disks released Ca2+ and PO4 ions
      at sustained levels requisite for remineralization to occur. The transformation
      of amorphous calcium phosphate into hydroxyapatite within the composites was also
      retarded, particularly in the case of amorphous calcium phosphate modified with
      ZrOCl2. Biaxial flexure strength values of composite disks showed that TEOS- and
      ZrOCl2-amorphous calcium phosphate-filled composites increased in strength by 33%
      and 21% before immersion and by 25% and 27% after immersion, respectively,
      compared to unmodified amorphous calcium phosphate composites (controls). All
      strength increases except TEOS after immersion were significant (p < 0.05).
      SIGNIFICANCE: Properly modified amorphous calcium phosphate fillers can be used
      to prepare bioactive composites with enhanced mechanical properties for more
      demanding dental applications without compromising their remineralizing
      potential.

PMID- 9170998
TI  - Dentin bond durability after three years using a dentin bonding agent with and
      without priming.
AB  - OBJECTIVES: This three-year study was conducted to evaluate the tensile bond
      strengths of a dual-cured bonding resin, with and without priming, to bovine
      dentin. METHODS: Superficial bovine dentin was conditioned with 37% phosphoric
      acid and left unprimed (control) or was primed with 5-NMSA. Clearfil Photobond
      (Kuraray Co., Japan) was placed and light-cured, a layer of Protect Liner
      (Kuraray Co.) was applied, cured, then covered with Photo Clearfil Bright (Kurary
      Co.) resin composite and cured. Bonds were stressed in tension to failure at 1 d,
      1 mon, 3 mon, 6 mon, 1 y and 3 y after preparation. Ten specimens were made for
      each group. Results were analyzed using one-way ANOVA and Duncan's multiple range
      test. Visual and SEM observations determined mode of failure and were analyzed
      using the Mann-Whitney U-test. Separate 1 d and 3 y specimens were fractured
      across the bonded interface and observed using a Field Emission SEM. After
      observation, the photomicrographs were compared for visual qualitative changes
      between the two time periods. RESULTS: The control (non-primed) group showed only
      a small decrease in bond strengths over 3 y, but in the primed group, a
      significant decrease was observed (p < 0.05). The bond strength of the non-primed
      group (5.2 MPa) was less than the primed group (10.6 MPa) at 1 d (p < 0.01), but
      by 3 y, the bonds of both groups were similar, 4.3 MPa and 5.5 MPa, respectively.
      Fractography indicated that only adhesive failure occurred in the control group.
      Failure in the primed group was cohesive in dentin initially, but shifted to the
      base or top of the hybrid layer after 1 y. Field Emission SEM observations showed
      hybrid layer formation in the primed group, but minimal resin infiltration in the
      control group. SIGNIFICANCE: Initially greater bond strengths were obtained for
      the primed group compared to the unprimed group (p < 0.01). However, by 3 y, the
      bond strength had decreased markedly in the primed group (p < 0.01), being almost
      the same for both groups. It was concluded that priming may only be useful to
      achieve strong bonding in the short term. These results may have significant
      implications related to clinical longevity of restorations.

PMID- 9170999
TI  - Mechanical behavior of thermo-responsive orthodontic archwires.
AB  - OBJECTIVES: This investigation was conducted to describe the mechanical behavior
      of thermo-responsive nitinol archwires in flexure at 5 degrees and 37 degrees C.
      METHODS: Four same-sized (but different force level) rectangular archwires were
      examined using a three-point bend test. Samples were tested at 5 degrees and 37
      degrees C. Linear regressions were fit to different segments of the load
      deflection plots. Regression parameters of the segments and other properties were
      statistically analyzed. RESULTS: Superelastic behavior was exhibited by all wires
      tested at 37 degrees but not at 5 degrees C. Permanent deformation was greater at
      5 degrees than 37 degrees. The initial slope of the load-deflection data averaged
      1230 g/mm at 37 degrees, which was significantly different from the average at 5
      degrees (500 g/mm). Loads at the apparent yield point and the loads at 1, 2, and
      3 mm of deflection were greater at 37 degrees C than at 5 degrees. While the
      slope and length of the superelastic region were not judged to be clinically
      significantly different, the average load of the superelastic region was
      significantly different: F300 (340 g) > F200 (250 g) > F100 (180 g) and Bioforce
      (180 g). When loaded at 5 degrees and then unloaded at 37 degrees, the mechanical
      hysteresis of the wires tested at 37 degrees and the permanent deformation of the
      wires tested at 5 degrees were reduced for all wires. SIGNIFICANCE: Nitinol wires
      are available with a variety of mechanical properties. The different mechanical
      properties of thermo-responsive wires at 5 degrees and 37 degrees C result in
      clinically useful shape-memory behavior. Utilizing the superelastic and shape
      memory features of thermo-responsive wires has clinical advantages.

PMID- 9171000
TI  - Surface texture changes of a composite brushed with "tooth whitening"
      dentifrices.
AB  - OBJECTIVES: The aim of this investigation was to evaluate the significance of
      selected surface texture parameters used to describe and quantify the effect of
      tooth brushing with various "tooth whitening" dentifrices on a resin composite
      surface in vitro. METHODS: Specimens of a microfil resin composite were brushed
      with selected dentifrices. Surface texture profiles were acquired and analyzed
      both pre- and post-brushing using a contact diamond stylus. The selected
      parameters chosen to describe the surface texture were Ra, Rz, Rpm and the Rpm:Rz
      ratio. Differences between toothpastes were assessed using an ANOVA and a
      multiple comparisons test, the Student Newman-Keuls procedure. P and t values
      were calculated to determine if any of the surface roughness parameters were
      significantly changed by brushing. RESULTS: The results indicate that there were
      significant changes in the surface texture of the resin composite following tooth
      brushing with the selected dentifrices. For example, the use of Clinomyn
      significantly increased the surface roughness of the resin composite, as measured
      by the Rz parameter, from 2.19 +/- 1.67 microns to 10.02 +/- 2.57 microns (p <
      0.05). In addition, the surface texture parameters chosen to describe the
      properties of the surface should reflect a knowledge of profile shape such as
      Rpm:Rz ratio, and care should be taken if measurements of surface texture of
      dental restorative materials are to be used as predictors of clinical
      performance. SIGNIFICANCE: All the toothpastes chosen for this investigation left
      a surface on the resin composite which may be prone to crack propagation during
      "vertical barrelling" movements generated during mastication. However, this may
      be more of a function of the rigidity of the restorative material rather than the
      surface left after tooth brushing.

PMID- 9171001
TI  - In vitro IL-1 beta and TNF-alpha release from THP-1 monocytes in response to
      metal ions.
AB  - OBJECTIVES: Previous studies have shown that biomaterials can activate
      macrophages to produce cytokines and promote an inflammatory response. Although
      the toxicity of many metal ions has been extensively investigated, little is
      known about the ability of these ions to alter cytokine release from macrophages.
      Yet the release of these ions from biomaterials has been well documented.
      Previous studies indicated that alterations in cytokine release might be expected
      because metal ions alter protein production in macrophages at sub-toxic
      concentrations. Thus, the hypothesis of this study was that metal ions can alter
      the secretion of cytokines from macrophages at sub-toxic concentrations. METHODS:
      The release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha
      (TNF-alpha) from macrophages was investigated when the macrophages were exposed
      to metal ions, with or without lipopolysaccharide (LPS), a component of dental
      plaque. Human THP-1 macrophages were exposed to ions of Ag, Au, Cu, Hg, and Ni
      for 24 h. In half of the cultures, LPS was added for the last 4 h. The release of
      IL-1 beta and TNF-alpha into the medium was measured using enzyme-linked
      immunosorbent assays. ANOVA and Tukey multiple comparison intervals were used to
      compare the various experimental conditions. RESULTS: None of the metal ions
      elevated the IL-1 beta or TNF-alpha levels after 24 h, but Ni ions significantly
      elevated the IL-1 beta and TNF-alpha levels after 72 h. With LPS added, Ag, Cu,
      and Ni significantly amplified the LPS-induced production of IL-1 beta but only
      Ni amplified the TNF-alpha response. These alterations in cytokine response
      occurred with metal ion concentrations which have been previously shown to be
      released from dental alloys in vitro and in vivo. SIGNIFICANCE: It appeared
      plausible that macrophage-cytokine mediated inflammatory responses may be altered
      by the presence of some metal ions in tissues, particularly Ni.

PMID- 9171002
TI  - Effect of light exposure on fracture toughness and flexural strength of light
      cured composites.
AB  - OBJECTIVES: This study was conducted to investigate the curing characteristics of
      light-cured composites and their related mechanical properties. METHODS: Single
      edge notch specimens [25 mm x 2.5 mm x 5 mm with a 5 mm notch (a/W = 0.5)] were
      prepared for fracture toughness measurements. For flexural strength testing, a
      stainless steel mold (25 mm x 2 mm x 2 mm) was used. Light-cured composites were
      condensed into the mold, and the middle third of the specimen was first activated
      for 30 s with 400 mW/cm2, for 60 s with 200 mW/cm2, or for 120 s with 100 mW/cm2.
      Then the remaining thirds were activated at the same intensity and curing time as
      the middle third. After 24 h storage in 37 degrees C water, three-point bending
      tests were performed with a span length of 20 mm at a crosshead speed of 0.5
      mm/min. A one-way ANOVA, followed by a Newman-Keuls test (p < 0.05), were used to
      compare the data obtained from each group to test the effect of the curing
      conditions. RESULTS: Fracture toughness, flexural strength, and flexural modulus
      varied with resin composites. Among the three curing conditions for each
      material, there were no significant differences in fracture toughness, flexural
      strength, or flexural modulus. SIGNIFICANCE: The fracture toughness and the
      flexural strength were the same when irradiations with the same amount of energy
      (light intensity multiplied by curing time) were used. It was found that, at
      lower light intensity, longer curing was required to provide comparable
      mechanical properties. An accumulated irradiation energy obtained through a
      product of the light intensity and curing time may serve as a guideline to
      produce samples exhibiting equivalent fracture toughness as well as flexural
      strengths.

PMID- 9171003
TI  - X-ray diffraction studies of oxidized high-palladium alloys.
AB  - OBJECTIVE: The purpose of this study was to use x-ray diffraction (XRD) to obtain
      new information about the oxide layers on four representative oxidized high
      palladium alloys. METHODS: Cast specimens of two Pd-Cu-Ga alloys and two Pd-Ga
      alloys, with both polished and etched surfaces and air-abraded surfaces, were
      subjected to oxidation procedures recommended by the manufacturers. The specimens
      were analyzed by x-ray diffraction using CuK alpha radiation, and the peaks were
      compared to appropriate Joint Committee on Powder Diffraction Standards (JCPDS).
      RESULTS: The surface preparation procedure had a profound effect on the phases
      present in the oxide layers. For the specimens that had been polished and etched,
      CuGa2O4 and beta-Ga2O3 were detected on the 79Pd-10Cu-9Ga-2Au alloy, whereas SnO2
      and CuGa2O4 were detected on the 76Pd-10Cu-5.5Ga-6Sn-2Au alloy. The oxide layers
      on both Pd-Cu-Ga alloys contained Cu2O1 and the oxide layer on the 76Pd-10Cu
      5.5Ga-6Sn-2Au alloy may contain beta-Ga2O3. The principal phase in the oxide
      layers on both Pd-Ga alloys that had been polished and etched was ln2O3, which
      exhibited extreme preferred orientation. No other phase was detected in the oxide
      layer on the 85Pd-10Ga-2Au-1Ag-1 ln alloy, whereas beta-Ga2O3 was found in the
      oxide layer on the 75Pd-6Ga-6Au-6Ag-6.5ln alloy. For the air-abraded specimens,
      beta-Ga2O2 was not present in the oxide layers on the Pd-Cu-Ga alloys, and beta
      Ga2O3 was the major phase in the oxide layers on the Pd-Ga alloys. Palladium
      oxide(s) in varying amounts were detected for both surface preparations of the Pd
      Cu-Ga alloys and for the air-abraded Pd-Ga alloys. Except for the 76Pd-10Cu-5.5Ga
      6Sn-2Au alloy, the oxide layer caused minimal change in the lattice parameter of
      the palladium solid solution compared to that for the as-cast alloy.
      SIGNIFICANCE: Knowledge of the phases found in the oxide layers on these high
      palladium alloys is of fundamental importance for interpreting differences in the
      adherence of dental porcelain to the metal substrates under static and dynamic
      conditions, and may provide guidance in the development of new high-palladium
      alloys with improved metal-ceramic bonding.

PMID- 9171004
TI  - Influence of criteria on the results of in vitro evaluation of microleakage.
AB  - OBJECTIVES: The aim of this study was to compare and explain the statistical
      methods employed to evaluate the in vitro sealing efficiency of adhesive
      restorative systems. METHODS: Two hundred and sixty sound freshly extracted human
      premolars were randomly divided into 13 groups. Standardized cavities were
      prepared, and the teeth were restored with 13 restorative systems. The teeth were
      thermocycled, immersed in dye, embedded in resin and sectioned. Five evaluation
      criteria were recorded: mean, median and mode of the data measured on each tooth,
      maximum dye penetration measurements on each tooth, and percentage of teeth in
      each group without any dye penetration. For each parameter, one-way ANOVAs and
      Duncan a posteriori tests were used to compare the 13 systems. RESULTS: The
      number of non-statistically different subgroups, pointed out by Duncan tests, was
      greater when the selected criterion was the maximum dye penetration (6 subgroups)
      or the percentage of teeth without any penetration (5 subgroups) than when the
      criterion was the median (3 subgroups), the mode or the mean (4 subgroups). The
      positioning of the 13 adhesive restorative systems established from the five
      criteria was different. Equivalent adhesion strategies revealing different
      experimental results indicate that other factors contribute to the final
      effectiveness of a particular system: clinical approach with respect to the
      formation of an elastic bonding layer, and shrinkage, physical and rheological
      properties of resin composite. SIGNIFICANCE: The results of these in vitro
      studies of dye penetration must be considered as comparisons and not as absolute
      conclusions. The maximum dye penetration measured on each tooth, which complies
      with the aim of the in vitro evaluation of sealing efficiency defined by Pashley
      (1990) and allows powerful statistical analysis of results, seems to be the best
      evaluation criterion.

PMID- 9171005
TI  - Consistency of resin composites for posterior use.
AB  - OBJECTIVES: The aim of this study was to compare a large set of resin composites
      suitable for application in stress-bearing areas on the basis of their
      consistency. METHODS: A variety of posterior resin composites were tested using
      an apparatus that was originally designed for determination of the consistency of
      elastomeric impression materials (ISO 4823, 1992). The consistency of a
      standardized volume of resin composite was tested in a dark room at 23 degrees C
      by loading the samples during 60 s with 1625 g. After loading, the circumference
      of each sample was determined by a digitizer. Results were analyzed using Tukey
      HSD multiple comparisons test and Student's t-tests. RESULTS: The consistency of
      different brands of composites varied considerably. P50 was the material with the
      thinnest consistency. Significant differences (p < 0.05) in consistency were
      found between the same brands of material which were applied directly out of the
      syringe or out of a preloaded tip. Loading a Centrix tip with one composite out
      of a syringe resulted in a thinner consistency of the material than when taken
      directly from the syringe. SIGNIFICANCE: A ranking of posterior resin composites
      is presented to enable a material selection based on consistency.

PMID- 9171006
TI  - Case report: an alternative treatment of deep traumatic overbite.
AB  - Multidisciplinary treatment of a case of deep traumatic overbite is presented.
      Complications of therapy and alternative treatment options are discussed. Methods
      used to provide a satisfactory aesthetic and functional outcome are described.

PMID- 9171007
TI  - Some factors affecting the transverse strength of repaired denture acrylic resin.
AB  - The aim of this study was to determine the transverse strength of repaired
      autopolymerising poly(methyl methacrylate) (PMMA) resin. The edge profile (EP) of
      the repair surface and the powder-to-liquid (PL) ratio of the autopolymerising
      acrylic resin used for repairs were studied to determine their effects on the
      transverse strength of rectangular test specimens. Neither the EP nor the PL
      ratio affected the transverse strength of the test specimens (EP: P = 0.692, PL:
      P = 0.575). However, the EP significantly affected the type of failure (P <
      0.001). The results suggest that autopolymerising PMMA of various PL ratios can
      be used to repair the fractured pieces of autopolymerising PMMA without affecting
      the strength of the repair.

PMID- 9171008
TI  - The effects of superstructure fit and loading on individual implant units: Part
      2. The effects of loading a superstructure with varying degrees of fit.
AB  - This study investigated force transmission in an implant supported bridge with
      varying degrees of fit. The project utilised an in vitro model of five implant
      fixtures mounted linearly and rigidly. These supported a well-fitting cast gold
      superstructure via implant abutments fitted with strain gauges so as to function
      as force transducers. Gaps of 10-110 microns were created at the middle and one
      terminal abutment and loads of 50N applied over the cantilever and 230N between
      the terminal abutments. Force distribution was uneven, compression, tension and
      torque observed, and loading of the cantilever noted to generate large forces.

PMID- 9171009
TI  - All-ceramic restorations: teaching in UK and Irish dental schools.
AB  - The teaching of all-ceramic restorations has been surveyed in the UK and Irish
      dental schools. Based on a 93% response, the findings indicate that the majority
      of undergraduate (pre-doctoral) students in UK and Irish dental schools gain
      clinical experience of all-ceramic restorations as part of their core teaching.
      While the 14 responding schools provide clinical instruction in all-ceramic
      crowns and veneers, only 12 schools were found to include instruction in all
      ceramic inlays and onlays. A wide range of ceramic systems are taught and there
      is general conformity in respect of the associated teaching in relation to liners
      and bases, the selection of impression materials and the use of luting systems,
      except in conjunction with all-ceramic crowns. The principal contraindications to
      all-ceramic restorations in undergraduate teaching were found to be poor oral
      hygiene and parafunctional activity (bruxing/clenching).

PMID- 9171010
TI  - Initial results of the Osteo Ti implant system in general dental practice.
AB  - It is the purpose of this paper to present the preliminary results of 370
      consecutively placed Osieo-Ti implants. Two stage screw form endosseous implants
      ranging in length from 7mm to 20mm in one mm increments were used. Four diameters
      of implant 2.75mm, 3.00mm, 3.75mm and 4.50mm were used to engage the maximum
      available width of bone. The larger, 3.75mm and 4.50mm diameter, implants were
      made from commercially pure titanium and the two smaller diameter, 2.75mm and
      3.00mm, implants were manufactured from titanium alloy. The overall success rate
      for 370 exposed functioning Osteo-Ti implants was 98.6%.

PMID- 9171011
TI  - Quantification of the configuration factor in Class I and II cavities and
      simulated cervical erosions.
AB  - The configuration factor of adhesive cavities is defined as the ratio of the
      restoration's bonded to unbonded (free) surfaces. Such a configuration factor was
      described, on ideal cavities, as having a potential value in predicting the
      behaviour of the restorations, because it is related to the restoration's
      capacity for relieving stress by flow. The aim of this study was to measure the
      configuration factor value for real Class I and II cavities and simulated
      cervical erosions prepared in molars. Ten Class I, five Class II cavities and
      seven cervical erosions were analysed using a computerised digitising system. The
      configuration factor values found were 4.03 +/- 0.33 for Class I cavities, 1.85
      +/- 0.59 for Class II cavities and 1.10 +/- 0.09 for simulated cervical erosions
      (P < 0.01).

PMID- 9171012
TI  - Case report: the use of a resin retained bridge with movable joint.
AB  - The use of resin retained bridge work is commonplace within dental practice.
      Factors that may affect long term success include the type of metal used and
      surface preparation, the resin, operator technique, the surface area of the
      tooth, differing movement of the abutment teeth and occlusal forces. A clinical
      case is reported in which a resin retained bridge with a movable joint was used
      to restore missing anterior teeth in a 15 year old girl with a developing
      occlusion.

PMID- 9171013
TI  - A retrospective study of the maintenance requirements associated with implant
      stabilised mandibular overdentures.
AB  - The maintenance requirements of a group of 58 patients, treated with the IMZ
      osseointegrated implant system and mandibular overdentures were investigated.
      Prostheses were retained by either bar and clip or separate stud attachments. The
      patients were followed up regularly for periods of between one and six years. The
      median number of maintenance procedures required per patient per year varied
      between 1-5. Detailed examination of the data revealed that a wide range of
      maintenance procedures was required, including replacement prostheses in 46% of
      cases. There were some differences related to the retentive elements used for the
      prostheses.

PMID- 9171014
TI  - The effects of pulsed ultraviolet and infra-red lasers on dental enamel.
AB  - To evaluate micromorphological changes seen in enamel following irradiation with
      pulsed lasers, extracted human teeth were treated with a TEA-CO2, an Er:YAG and
      an ArF laser systems. Light and scanning electron microscopic studies demonstrate
      that the Er:YAG laser produces a zone of microcracks in the subsurface area.
      While TEA-CO2 laser irradiation results mostly in surface melting, the Er:YAG
      laser produces a roughened enamel surface. After ArF laser irradiation a
      retentive surface appears, accompanied by some melting effects and an increased
      porosity. The observed results of all the employed laboratory type lasers varied
      over a wide range due to the widespread biologic differences in tooth structures.

PMID- 9171015
TI  - Colorimetric analysis as a means of quality control for dental ceramic materials.
AB  - In this in-vitro study colorimetric analysis using the CIELAB-system was applied
      to two all-ceramic materials in shades A1 and A2. The material for the 96
      specimens was taken from three production batches and examined
      spectrophotometrically after firing. For both materials the firing-process led to
      only small colour differences (average DE-value < 2.2). Between the three batches
      of each material, significantly higher, visually perceivable colour differences
      were detected. The results revealed that the Castor system is capable of
      producing high-precision colour measurements. The use of spectrophotometric
      devices is recommended as a means of quality control in order to decrease colour
      tolerances between different batches of the same material.

PMID- 9171016
TI  - MR-imaging of the TMJ: artefacts caused by dental alloys.
AB  - The aim of the study was to investigate the influence of dental alloys and their
      components on magnetic resonance imaging of the temporomandibular joint. A
      plaster and a water- filled acrylic resin phantom - representing the disc and the
      condyle of the TMJ - were used. Cylindrical crow-type samples of 13 alloys and 14
      pure substances were investigated. All alloys were examined with regard to their
      magnetic susceptibility, using a vibrating sample magnetometer. Metallic
      artefacts appeared on spin-echo technique as distortions, and on gradient-echo
      technique signal loss could be observed. Precious alloys were shown to be
      diamagnetic. The non precious alloys we investigated were paramagnetic.
      Paramagnetic alloys with a magnetic molar-susceptibility Cmol > 2000 x10(-6)
      cm3/mol can produce clinically relevant artefacts.

PMID- 9171017
TI  - A finite element analysis of a mandibular canine as a denture abutment.
AB  - A two dimensional finite element model was made of a mandibular canine and its
      supporting bone. The model was used to show stress values associated with loading
      the tooth as a partial denture abutment before and after modification to include
      rest seat preparations in different positions. Axial load produced a low pattern
      of stress while load on the unprepared tooth produced a very high pattern of
      stress. The effectiveness of rest seats in reducing stress in the alveolar bone
      was confirmed.

PMID- 9171018
TI  - Case report: prosthodontic treatment for the transmandibular implant.
AB  - The Transmandibular Implant is a transosteal implant developed to help improve
      masticatory function in patients with severe mandibular atrophy. It is a
      functional implant with a rigid box frame design which allows acceptance of
      masticatory loads in mandibles with minimal bone height. The implant is
      fabricated of a gold alloy and is placed between the mental foramina from a
      submental approach. The prosthesis is fabricated as an overdenture and retention
      is obtained by means of retention sleeves adapted to Dolder bar segments of the
      superstructure. Denture comfort and function can be greatly improved for patients
      with severely resorbed mandibles.

PMID- 9171019
TI  - Evaluation of the biocompatibility of various dental alloys: Part I--Toxic
      potentials.
AB  - The biocompatibility of a high-gold alloy (Iropal W), two low-gold alloys
      (Argenco 9 and Gold EWL-G), one palladium alloy (Argipal), two palladium-silver
      alloys (Argenco 23 and EWL-G), one chrome-nickel alloy (Wiron-88), two chrome
      cobalt alloys (Wironium and Wirocast) and a 22 carat gold alloy were evaluated
      histopathologically with the subcutaneous implantation technique. Cast discs of
      the materials were implanted for 15, 30 or 60 days in 111 rats. Mildest responses
      occurred to 22 carat gold alloy. The most vigorous responses were observed in the
      chrome-nickel alloy samples. The high-gold alloy and the palladium groups showed
      reactions quite similar to those of the 22 carat gold. However, the low-gold
      group and the palladium-silver alloys ranked between the basic metal alloy and
      the precious metal alloy groups.

PMID- 9171020
TI  - The pattern of usage of dentine pins.
AB  - A survey of 1394 dentine pin placements, completed by 37 selected practitioners
      over a period of three months provides information relevant to the teaching of
      pin techniques and to future research on alternatives to the use of dentine pins
      in the restoration of severely compromised teeth. In this survey, most direct pin
      retained restorations were found to be placed in the mandibular permanent molar
      teeth of patients 20-39 years of age. Such restorations were frequently found to
      include only one pin, which in about 50% of cases was bent or shortened. Overall,
      difficulties with pins occurred during one in twenty pin placements. The long
      term consequences of the use of pins remains to be investigated.

PMID- 9171021
TI  - The shortened dental arch--to restore or not.

PMID- 9171022
TI  - What do patients expect from extensive restorative dental treatment?
AB  - A specially designed questionnaire was sent to 489 patients waiting for major
      prosthodontic treatment. Further material regarding these patients was collected
      from treatment files and public records. The study aimed to describe the patient
      group from a socio-economic standpoint and to identify factors affecting the
      patient's expectations concerning prosthodontic treatment. The overall response
      rate was 84.2%. The patient group was found to differ significantly from the
      general population only in regard to educational level which was lower. The study
      indicated that patients expected the forthcoming prosthodontic therapy to enhance
      their general well-being. In the subgroup of patients awaiting implants,
      expectations of a better chewing function were salient. Therefore, from the
      results of this study it is not possible to extrapolate uncritically to other
      groups and other conditions. A number of economical, cultural and social
      conditions could have a major impact on attitudes regarding prosthodontic
      treatment.

PMID- 9171023
TI  - A method for scoring denture plaque.
AB  - Many studies have reported on the comparative efficiency of denture cleaning
      materials in their ability to remove deposits from dentures, but because of the
      variety of scoring methods used it is often difficult to make direct comparisons
      between materials. It is important that any measurements obtained should not only
      be accurate, reliable and reproducible but that inter-examiner error should be
      kept to a minimum. In this work three operators were asked to score 'blind' the
      total amount of disclosed plaque on a whole denture using a 0-10 scale. The
      overall conclusions of this test was that of poor inter-examiner agreement. A
      second test was therefore undertaken at a later date using the same three
      operators and protocol but on this occasion each surface of the denture was
      evaluated by reference to a series of standard reference dentures painted to
      simulate plaque scores in the 0-10 range. This test showed there to be no
      significant difference in the plaque scores recorded by the three operators and
      that the plaque scores recorded on the polished surfaces were significantly lower
      than those on the teeth and fitting surfaces (F = 10.55, P < 0.001).

PMID- 9171024
TI  - An evaluation of the fit of porcelain inlays.
AB  - The effect of die spacer usage and three different porcelain build up techniques
      on inlay fit were investigated by impression wash methods and image analysis of
      sectioned replicas. All inlays were produced on machined cavities. Data from the
      impression wash technique indicated a mean misfit value of just over 100 microns.
      Image analysis showed a smaller mean misfit of 40-60 microns. In general, the use
      of die spacer resulted in a poorer fit and there were no significant differences
      between methods of porcelain application detected by either method.

PMID- 9171025
TI  - Effect of light intensity on polymerisation of three composite resins.
AB  - The polymerisation ability of twelve light activation units, a mixture of new and
      old, was assessed by micro-hardness evaluation of samples of three composite
      resins cured with the lights. Light intensity was assessed using a commercially
      available band held dental radiometer. Intensity values were representative of
      the range of intensities that may be found in clinical practice. When a 2 mm
      thick sample of a microfilled composite was cured for 40s less than half of the
      light units evaluated produced an acceptable lower surface polymerisation. All
      but one of the light units tested produced a satisfactory lower surface cure with
      the monomodal and the hybrid composites. For the products tested material
      composition was an important factor in regard to the ability to cure a 2 mm thick
      increment of material with a 40s irradiation time. A significant correlation was
      found between lower surface hardness and light intensity. Standardising the area
      of the light sensing device of the hand held radiometer with respect to the
      diameter of the specimen to be cured improved the correlation between light
      intensity and lower surface micro-hardness.

PMID- 9171026
TI  - The development of a simple test method to characterise the compliance and
      viscoelasticity of long-term soft lining materials.
AB  - A simple test, based on the measurement of depth of penetration, has been devised
      to characterise long-term soft lining materials. Inter-laboratory testing has
      shown the method to be reproducible and to be capable of comparing and
      contrasting the compliance and viscoelastic behaviour of commercially available
      materials. Additional results emphasise the point that it is imperative to
      control the testing temperature, especially for the soft acrylic materials.

PMID- 9171027
TI  - Effect of powder-to-liquid ratio on the distortion of repaired denture acrylic
      resin.
AB  - The aim of this study was to determine the distortion of repaired
      autopolymerising poly(methylmethacrylate) (PMMA) resin. Eighteen rectangular test
      specimens with a 45-degree edge profile repair surface were repaired with
      autopolymerising PMMA using different powder-to-liquid (PL) ratios. None of the
      test specimens distorted during repair, although microscopical examination showed
      porosities which may have been due to polymerisation shrinkage. The results
      suggest that autopolymerising PMMA with various PL ratios can be used to repair
      fractured pieces of PMMA without affecting the distortion of the specimen.

PMID- 9171028
TI  - The role of specialist associations and societies in clinical dentistry.

PMID- 9171029
TI  - A strategy for planning restorative dental care. British Society for Restorative
      Dentistry.

PMID- 9171030
TI  - Evaluation of the biocompatibility of various dental alloys: Part 2--Allergenical
      potentials.
AB  - The metal alloys which were investigated histopathologically in the first part of
      this study, were examined with respect to their allergic potentials using the
      patch test. Results from 60 subjects (aged 17-23) were evaluated following
      exposure to nickel sulphate, potassium dichromate, silver nitrate, cobalt
      nitrate, copper sulphate, palladium chloride, platinum chloride and gold
      chloride. Nickel sulphate produced the most vigorous allergic response whereas
      gold chloride showed the least of all. The remaining solutions were ranked in
      decreasing order of severity as follows: potassium dichromate, cobalt nitrate,
      silver nitrate, copper sulphate, palladium chloride and platinum chloride. Patch
      testing is indicated in any patient with a history of allergy or sensitivity to a
      metal. The use of nickel containing alloys in such patients should also be
      avoided.

PMID- 9171031
TI  - Factors associated with shear bond strength of composite resin to human enamel.
AB  - The preparation of enamel surfaces before etching by removing 0.5 mm of surface
      tooth structure is common-place in modern restorative dentistry. This study was
      designed to measure and compare the shear bond strength of composite resin bonded
      to prepared and unprepared enamel using various proprietary bonding systems. The
      analysed results failed to show significant differences between the shear bond
      strengths of the prepared and unprepared enamel specimens. Conditioning enamel
      surfaces for 60 seconds using 2.5% nitric acid where the solution was allowed to
      desiccate, resulted in significantly lower bond strengths compared to the other
      regimes. A correlation of the etchant pH with the mean shear bond strength of the
      adhesive systems to enamel was observed. The surface topography of the etched
      enamel surfaces correlated moderately well with the bond strengths obtained.

PMID- 9171032
TI  - Roentgencraniometric indicators of the position of the occlusal plane in natural
      and artificial dentitions.
AB  - The angular relationship between the occlusal plane and six variants of Camper's
      plane used in clinical practice were investigated on 41 lateral cephalometric
      radiographs. The line A-T1, connecting the lower border of the ala with the upper
      border of the tragus is recommended in establishing the occlusal plane in
      patients with a Skeletal Class 2 jaw relationship, the A-T2, running through the
      middle of the tragus, in patients with a Skeletal Class 1, and the line A-T3,
      running through the lower border of the tragus in patients with the Skeletal
      Class 3 jaw relationship.

PMID- 9171033
TI  - Assessment of a prototype battery operated wax-knife for domiciliary and surgery
      use.
AB  - The aims of this study were to examine a prototype battery operated wax-knife,
      assess the extent to which manufacturer's claims have been achieved and determine
      its potential for clinical use. The mean time required for the wax-knife to
      achieve an operating temperature of 150 degrees C was 20.2(+/-4.3) s. The mean
      operating temperature of the ceramic blade was 155.4(+/-3.9) degrees C, range 150
      degrees C to 162 degrees C. The mean usage time following full battery recharge
      was 42 (+/-2) minutes. The wax-knife provided a direct heating tool which
      retained many of the characteristics of the traditional wax-knife and was
      suitable for use in the surgery and in domiciliary situations.

PMID- 9171034
TI  - Observations on 25 patients treated with ball-retained overdentures using the
      Astra Tech implant system.
AB  - Twenty-five adult patients with fully edentulous jaws, aged from 44 to 80 years
      were treated with seventy-one 3.5 mm diameter Astra Tech dental implants in the
      parasymphseal region. The length of these implants varied from 9 mm to 15 mm.
      Either two or three implants were inserted, subsequently exposed after a minimum
      period of 3 months, abutments and ball attachments placed. Full lower dentures
      incorporating gold alloy housings for ball-attachments were constructed. The
      average time that the implants were in situ was 4 years and 2 months, ranging
      from 1 year 3 months to 5 years and 7 months. Of the 71 implants placed, 67
      achieved osseointegration-a success rate of 94%. The main complication was that
      of the ball-attachments becoming loose.

PMID- 9171035
TI  - Retrospective audit of patients with advanced toothwear restored with removable
      partial dentures.
AB  - The dental records of 50 patients with advanced tooth wear restored with
      removable prostheses were examined. Retrospective data were collected with regard
      to source of referral, presenting complaint, aetiological factors, clinical
      features, dentures provided, details of failures and maintenance. The maximum
      follow up period was three years. The ratio of male to female patients was 4:1
      and the age range 31-75 years. Failures were recorded in 38% of patients with
      provisional and 64% with definitive dentures. The most common failure was
      fracture or wear of the incisal or occlusal surfaces. The majority of failures
      were addressed by adjustment of the dentures and the audit confirmed the need for
      regular maintenance.

PMID- 9171036
TI  - In defense of digitized images.

PMID- 9171037
TI  - Ethics and insurance billings.

PMID- 9171038
TI  - Sjogren's syndrome: diagnosis and management of oral complications.
AB  - Sjogren's syndrome, a common autoimmune disease process, is characterized by
      destruction of exocrine (including the lacrimal and salivary) glands. Patients
      with this disorder may initially complain of a dry mouth or have rapid onset of
      new carious lesions. Here, a case of Sjogren's syndrome is presented that was
      initially diagnosed because of dental complaints, and long-term treatment of
      Sjogren's patients is discussed.

PMID- 9171039
TI  - Uses and properties of current glass ionomer cements: a review.
AB  - Glass ionomer cements have been used for a variety of restorative purposes.
      Recently, the formulation of these and other restorative materials has changed
      rapidly, so it is difficult to keep pace with the literature concerning effective
      use. A major modification to glass ionomer cements has been incorporation of
      resin components. This and other modifications over the years have changed some
      handling characteristics and physical properties of glass ionomer cements. A
      general review of some changes is reported here.

PMID- 9171040
TI  - Latex-induced asthma in a dental assistant.
AB  - In this case report, latex-induced asthma is described in a dental assistant with
      an associated history of contact dermatitis, contact urticaria, and rhinitis. She
      switched to vinyl gloves, which eliminated her cutaneous symptoms, but her
      respiratory symptoms continued. Skin-testing to latex was strongly positive.
      Methacholine challenge and peak expiratory flow rates (PEFR) were abnormal during
      the workweek but normalized after a two-week vacation. Nebulized latex was
      implicated in the development of occupational asthma, and personal latex
      avoidance measures did not prevent the condition.

PMID- 9171041
TI  - Otodental syndrome.
AB  - Otodental dysplasia, a form of ectodermal dysplasia, is characterized by abnormal
      dental crown morphology and sensorineural hearing loss. A variety of dental
      abnormalities are prominent features of this syndrome--most notably gigantic,
      bulbous posterior teeth. In this case, a sibling is identifies in a family with
      otodental syndrome that had been diagnosed earlier. A unique opportunity is
      provided to view the intact adult dentition and possible complications for dental
      treatment.

PMID- 9171042
TI  - Lingual osseous choristoma.
AB  - Osseous choristoma represents normal bony tissue in an abnormal location. A case
      report of a lingual osseous choristoma and a literature review are presented.

PMID- 9171043
TI  - Fractured-tooth fragment reattachment.
AB  - Traumatic injuries with loss of tooth fragments in the incisor region are common,
      especially among children and adolescents. Reattachment of tooth fragments is an
      important technique for restoring fractured teeth and provides advantages over
      resin-composite restoration, including better esthetic appearance, maintenance of
      tooth form and color, minimal tooth loss, increased wear resistance, and, thus,
      improved function.

PMID- 9171044
TI  - An unusual case of cervical root resorption.
AB  - Supraosseous extracanal invasive root resorption was diagnosed based on a
      radiographic survey, clinical examination, and microscopic examination of pulpal
      and exophytic soft-tissue specimens. Microscopic pulpal examination showed little
      or no evidence of significant inflammation. This resorptive process demonstrates
      extensive noncarious destruction of dentin without affecting pulpal health.

PMID- 9171045
TI  - Efficacy of a new electronic toothbrush in removing bacterial dental plaque in
      young adults.
AB  - Although a high level of oral cleanliness is essential for long-term maintenance
      of dental health, many people cannot maintain good oral hygiene consistently. A
      new electronic toothbrush has been developed that induces a small electric charge
      onto tooth surfaces. This charge damages electrostatic bonding of plaque proteins
      to tooth surfaces; thus, plaque removal is enhanced while the toothbrush is used.
      Young men were issued identical toothbrushes; some were electrically active.
      Plaque levels were assessed at baseline, and after two and four weeks,
      concurrently with oral-hygiene instruction and professional prophylaxis. The
      electrically active toothbrushes demonstrated better plaque removal than the
      inactive toothbrushes. This better performance was statistically significant
      linguopalatally, indicating that significantly more plaque was removed where
      mechanical access was poorest. Thus, the electrical activity of this toothbrush
      significantly enhances plaque removal where toothbrushing access is limited.

PMID- 9171046
TI  - Addressing the caries dilemma: detection and intervention with a disclosing
      agent.
AB  - This study was undertaken after a joint symposium (in March 1993) of the
      operative section of the American Association for Dental Research and the
      cariology and diagnostic groups of the International Association for Dental
      Research called for investigation into new diagnostic modalities to determine and
      standardize criteria for reliable caries detection. As the incidence, prevalence,
      and progression rate of caries decline in Western countries, concern grows about
      the technical and clinical development involved in teaching dental students to
      diagnose the status and stage of carious lesions reliably. In this in vitro
      study, the disclosing agent Cari-D-Tech (Gresco Product Inc., Stafford, TX) was
      tested to validate its efficacy based on histologic specificity as its mode of
      detecting infected dentin. Extracted human teeth with clinical caries were
      sectioned into representative paired samples to create two groups. After dental
      excavation, with or without use of the disclosing agent, the teeth were coded to
      identify the method of removing caries. The coded samples were prepared to
      provide histologic specimens. Results showed that all infected dentin was
      removed, demonstrating the efficacy of this disclosing agent.

PMID- 9171047
TI  - Bilateral oral melanoacanthoma.
AB  - A case of bilateral oral melanoacanthoma involving the buccal mucosa is reported.
      This rare lesion, most often found in young black persons, is suggested here to
      be reactive in nature.

PMID- 9171055
TI  - The origin recognition complex, SIR1, and the S phase requirement for silencing.
AB  - Silencing of transcription in Saccharomyces cerevisiae has several links to DNA
      replication, including a role for the origin recognition complex (ORC), the DNA
      replication initiator, in both processes. In addition, the establishment of
      silencing at the HML and HMR loci requires cells to pass through the S phase of
      the cell cycle. Passage through S phase was required for silencing of HMR even
      under conditions in which ORC itself was no longer required. The requirement for
      ORC in silencing of HMR could be bypassed by tethering the Sir1 protein to the
      HMR-E silencer. However, ORC had a Sir1-independent role in transcriptional
      silencing at telomeres. Thus, the role of ORC in silencing was separable from its
      role in initiation, and the role of S phase in silencing was independent of
      replication initiation at the silencers.

PMID- 9171056
TI  - Orientation selectivity in pinwheel centers in cat striate cortex.
AB  - In primary visual cortex of higher mammals neurons are grouped according to their
      orientation preference, forming "pinwheels" around "orientation centers."
      Although the general structure of orientation maps is largely resolved, the
      microscopic arrangement of neuronal response properties in the orientation
      centers has remained elusive. The tetrode technique, enabling multiple single
      unit recordings, in combination with intrinsic signal imaging was used to reveal
      the fine-grain structure of orientation maps in these locations. The results show
      that orientation centers represent locations where orientation columns converge
      containing normal, sharply tuned neurons of different orientation preference
      lying in close proximity.

PMID- 9171057
TI  - Genetic feminization of pheromones and its behavioral consequences in Drosophila
      males.
AB  - Pheromones are intraspecific chemical signals important for mate attraction and
      discrimination. In the fruit fly Drosophila melanogaster, hydrocarbons on the
      cuticular surface of the animal are sexually dimorphic in both their occurrence
      and their effects: Female-specific molecules stimulate male sexual excitation,
      whereas the predominant male-specific molecule tends to inhibit male excitation.
      Complete feminization of the pheromone mixture produced by males was induced by
      targeted expression of the transformer gene in adult oenocytes (subcuticular
      abdominal cells) or by ubiquitous expression during early imaginal life. The
      resulting flies generally exhibited male heterosexual orientation but elicited
      homosexual courtship from other males.

PMID- 9171059
TI  - Substantial genetic influence on cognitive abilities in twins 80 or more years
      old.
AB  - General and specific cognitive abilities were studied in intact Swedish same-sex
      twin pairs 80 or more years old for whom neither twin had major cognitive,
      sensory, or motor impairment. Resemblance for 110 identical twin pairs
      significantly exceeded resemblance for 130 fraternal same-sex twin pairs for all
      abilities. Maximum-likelihood model-fitting estimates of heritability were 62
      percent for general cognitive ability, 55 percent for verbal ability, 32 percent
      for spatial ability, 62 percent for speed of processing, and 52 percent for
      memory. There was also evidence for the significant influence of idiosyncratic
      experience as the environmental component that most determines individual
      differences in cognitive abilities late in life.

PMID- 9171060
TI  - An aquaporin-like gene required for the Brassica self-incompatibility response.
AB  - Self-incompatibility in Brassica refers to the rejection of self-related pollen
      and is mediated by a receptor protein kinase localized to the plasma membrane of
      the stigma epidermis in the flower. The recessive mutation mod eliminates self
      incompatibility in the stigma. In mod mutants, self-compatibility was shown to be
      associated with the absence of transcripts encoded by an aquaporin-related gene.
      This observation suggests that a water channel is required for the self
      incompatibility response of Brassica, which is consistent with the concept that
      regulation of water transfer from the stigma to pollen is a checkpoint in the
      early events of pollination in the crucifer family.

PMID- 9171061
TI  - Aluminum tolerance in transgenic plants by alteration of citrate synthesis.
AB  - Aluminum when in soluble form, as found in acidic soils that comprise about 40
      percent of the world's arable land, is toxic to many crops. Organic acid
      excretion has been correlated with aluminum tolerance in higher plants.
      Overproduction of citrate was shown to result in aluminum tolerance in transgenic
      tobacco (Nicotiana tabacum) and papaya (Carica papaya) plants.

PMID- 9171062
TI  - Isolation of a bacterium that reductively dechlorinates tetrachloroethene to
      ethene.
AB  - Tetrachloroethene is a prominent groundwater pollutant that can be reductively
      dechlorinated by mixed anaerobic microbial populations to the nontoxic product
      ethene. Strain 195, a coccoid bacterium that dechlorinates tetrachloroethene to
      ethene, was isolated and characterized. Growth of strain 195 with H2 and
      tetrachloroethene as the electron donor and acceptor pair required extracts from
      mixed microbial cultures. Growth of strain 195 was resistant to ampicillin and
      vancomycin; its cell wall did not react with a peptidoglycan-specific lectin and
      its ultrastructure resembled S-layers of Archaea. Analysis of the 16S ribosomal
      DNA sequence of strain 195 indicated that it is a eubacterium without close
      affiliation to any known groups.

PMID- 9171063
TI  - Membrane and morphological changes in apoptotic cells regulated by caspase
      mediated activation of PAK2.
AB  - Apoptosis of Jurkat T cells induced the caspase-mediated proteolytic cleavage of
      p21-activated kinase 2 (PAK2). Cleavage occurred between the amino-terminal
      regulatory domain and the carboxyl-terminal catalytic domain, which generated a
      constitutively active PAK2 fragment. Stable Jurkat cell lines that expressed a
      dominant-negative PAK mutant were resistant to the Fas-induced formation of
      apoptotic bodies, but had an enhanced externalization of phosphatidylserine at
      the cell surface. Thus, proteolytic activation of PAK2 represents a guanosine
      triphosphatase-independent mechanism of PAK regulation that allows PAK2 to
      regulate morphological changes that are seen in apoptotic cells.

PMID- 9171064
TI  - Immediate coronary angiography in survivors of out-of-hospital cardiac arrest.
AB  - BACKGROUND: The incidence of acute coronary-artery occlusion among patients with
      sudden cardiac arrest outside of the hospital is unknown, and the role of
      reperfusion therapy has not been determined. We therefore performed immediate
      coronary angiography and angioplasty when indicated in survivors of out-of
      hospital cardiac arrest. METHODS: Between September 1994 and August 1996,
      coronary angiography was performed in 84 consecutive patients between the ages of
      30 and 75 years who had no obvious noncardiac cause of cardiac arrest. RESULTS:
      Sixty of the 84 patients had clinically significant coronary disease on
      angiography, 40 of whom had coronary-artery occlusion (48 percent). Angioplasty
      was attempted in 37 patients and was technically successful in 28. Clinical and
      electrocardiographic findings, such as the occurrence of chest pain and the
      presence of ST-segment elevation, were poor predictors of acute coronary-artery
      occlusion. The in-hospital survival rate was 38 percent. Multivariate logistic
      regression analysis revealed that successful angioplasty was an independent
      predictor of survival (odds ratio, 5.2; 95 percent confidence interval, 1.1 to
      24.5; P=0.04). CONCLUSIONS: Acute coronary-artery occlusion is frequent in
      survivors of out-of-hospital cardiac arrest and is predicted poorly by clinical
      and electrocardiographic findings. Accurate diagnosis by immediate coronary
      angiography can be followed in suitable candidates by coronary angioplasty, which
      seems to improve survival.

PMID- 9171065
TI  - Epidural corticosteroid injections for sciatica due to herniated nucleus
      pulposus.
AB  - BACKGROUND: Although epidural corticosteroid injections are commonly used for
      sciatica, their efficacy has not been established. METHODS: In a randomized,
      double-blind trial, we administered up to three epidural injections of
      methylprednisolone acetate (80 mg in 8 ml of isotonic saline) or isotonic saline
      (1 ml) to 158 patients with sciatica due to a herniated nucleus pulposus. All
      patients had Oswestry disability scores higher than 20 (on a scale of 1 to 100,
      with scores of 20 or less indicating minimal disability, and higher scores
      greater disability). RESULTS: At three weeks, the Oswestry score had improved by
      a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group (95
      percent confidence interval for the difference, -7.1 to 2.2). Differences in
      improvements between the groups were not significant, except for improvements in
      the finger-to-floor distance (P=0.006) and sensory deficits (P=0.03), which were
      greater in the methylprednisolone group. After six weeks, the only significant
      difference was the improvement in leg pain, which was greater in the
      methylprednisolone group (P=0.03). After three months, there were no significant
      differences between the groups. The Oswestry score had improved by a mean of 
      17.3 in the methylprednisolone group and -15.4 in the placebo group (95 percent
      confidence interval for the difference, -9.3 to 5.4). At 12 months, the
      cumulative probability of back surgery was 25.8 percent in the methylprednisolone
      group and 24.8 percent in the placebo group (P=0.90). CONCLUSIONS: Although
      epidural injections of methylprednisolone may afford short-term improvement in
      leg pain and sensory deficits in patients with sciatica due to a herniated
      nucleus pulposus, this treatment offers no significant functional benefit, nor
      does it reduce the need for surgery.

PMID- 9171067
TI  - Images in clinical medicine. Latrodectus mactans.

PMID- 9171066
TI  - Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's
      lymphoma associated with human immunodeficiency virus infection. National
      Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.
AB  - BACKGROUND: Reduced doses of cytotoxic chemotherapy or standard-dose therapy plus
      a myeloid colony-stimulating factor decreases hematologic toxicity and its
      complications in patients with non-Hodgkin's lymphoma associated with infection
      with the human immunodeficiency virus (HIV). However, the effect of reducing the
      doses of cytotoxic chemotherapeutic agents on clinical outcome is not known.
      METHODS: We randomly assigned 198 HIV-seropositive patients with previously
      untreated, aggressive non-Hodgkin's lymphoma to receive standard-dose therapy
      with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and
      dexamethasone (m-BACOD) along with granulocyte-macrophage colony-stimulating
      factor (GM-CSF; n=94) or reduced-dose m-BACOD with GM-CSF administered only as
      indicated (n=98). RESULTS: A complete response was achieved in 39 of the 94
      assessable patients assigned to low-dose therapy (41 percent) and in 42 of the 81
      assessable patients assigned to standard-dose therapy (52 percent, P= 0.56).
      There were no significant differences in overall or disease-free survival; median
      survival times were 35 weeks for patients receiving low-dose therapy and 31 weeks
      for those receiving standard-dose therapy (risk ratio for death in the standard
      dose group=1.17; 95 percent confidence interval, 0.84 to 1.63; P=0.25). Toxic
      effects of chemotherapy rated grade 3 or higher occurred in 66 of 94 patients
      assigned to standard-dose therapy (70 percent) and 50 of 98 patients assigned to
      low-dose treatment (51 percent, P=0.008). Hematologic toxicity accounted for the
      difference. CONCLUSIONS: As compared with treatment with standard doses of
      cytotoxic chemotherapy (m-BACOD), reduced doses caused significantly fewer
      hematologic toxic effects yet had similar efficacy in patients with HIV-related
      lymphoma. Dose-modified chemotherapy should be considered for most HIV-infected
      patients with lymphoma.

PMID- 9171068
TI  - The risk of birth defects among children of Persian Gulf War veterans.
AB  - BACKGROUND: There has been suspicion that service in the Persian Gulf War
      affected the health of veterans adversely, and there have been claims of an
      increased rate of birth defects among the children of those veterans. METHODS: We
      evaluated the routinely collected data on all live births at 135 military
      hospitals in 1991, 1992, and 1993. The data base included up to eight diagnoses
      from the International Classification of Diseases, 9th Revision, Clinical
      Modification (ICD-9-CM) for each birth hospitalization, plus information on the
      demographic characteristics and service history of the parents. The records of
      over 75,000 newborns were evaluated for any birth defect (ICD-9-CM codes 740 to
      759, plus neoplasms and hereditary diseases) and for birth defects defined as
      severe on the basis of the specific diagnoses and the criteria of the Centers for
      Disease Control and Prevention. RESULTS: During the study period, 33,998 infants
      were born to Gulf War veterans and 41,463 to non-deployed veterans at military
      hospitals. The overall risk of any birth defect was 7.45 percent, and the risk of
      severe birth defects was 1.85 percent. These rates are similar to those reported
      in civilian populations. In the multivariate analysis, there was no significant
      association for either men or women between service in the Gulf War and the risk
      of any birth defect or of severe birth defects in their children. CONCLUSIONS:
      This analysis finds no evidence of an increase in the risk of birth defects among
      the children of Gulf War veterans.

PMID- 9171069
TI  - Multiple myeloma.

PMID- 9171070
TI  - Our endangered integrity--it can only get worse.

PMID- 9171071
TI  - Rationing by any other name.

PMID- 9171072
TI  - Disability and physician-assisted suicide.

PMID- 9171074
TI  - Eukaryotic release factor 1 (eRF1) abolishes readthrough and competes with
      suppressor tRNAs at all three termination codons in messenger RNA.
AB  - It is known from experiments with bacteria and eukaryotic viruses that
      readthrough of termination codons located within the open reading frame (ORF) of
      mRNAs depends on the availability of suppressor tRNA(s) and the efficiency of
      termination in cells. Consequently, the yield of readthrough products can be used
      as a measure of the activity of polypeptide chain release factor(s) (RF), key
      components of the translation termination machinery. Readthrough of the UAG codon
      located at the end of the ORF encoding the coat protein of beet necrotic yellow
      vein furovirus is required for virus replication. Constructs harbouring this
      suppressible UAG codon and derivatives containing a UGA or UAA codon in place of
      the UAG codon have been used in translation experiments in vitro in the absence
      or presence of human suppressor tRNAs. Readthrough can be virtually abolished by
      addition of bacterially-expressed eukaryotic RF1 (eRF1). Thus, eRF1 is functional
      towards all three termination codons located in a natural mRNA and efficiently
      competes in vitro with endogenous and exogenous suppressor tRNA(s) at the
      ribosomal A site. These results are consistent with a crucial role of eRF1 in
      translation termination and forms the essence of an in vitro assay for RF
      activity based on the abolishment of readthrough by eRF1.

PMID- 9171073
TI  - Trinucleotide repeats associated with human disease.
AB  - Triplet repeat expansion diseases (TREDs) are characterized by the coincidence of
      disease manifestation with amplification of d(CAG. CTG), d(CGG.CCG) or d(GAA.TTC)
      repeats contained within specific genes. Amplification of triplet repeats
      continues in offspring of affected individuals, which generally results in
      progressive severity of the disease and/or an earlier age of onset, phenomena
      clinically referred to as 'anticipation'. Recent biophysical and biochemical
      studies reveal that five of the six [d(CGG)n, d(CCG)n, (CAG)n, d(CTG)n and
      d(GAA)n] complementary sequences that are associated with human disease form
      stable hairpin structures. Although the triplet repeat sequences d(GAC)n and
      d(GTC)n also form hairpins, repeats of the double-stranded forms of these
      sequences are conspicuously absent from DNA sequence databases and are not
      anticipated to be associated with human disease. With the exception of d(GAG)n
      and d(GTG)n, the remaining triplet repeat sequences are unlikely to form hairpin
      structures at physiological salt and temperature. The details of hairpin
      structures containing trinucleotide repeats are summarized and discussed with
      respect to potential mechanisms of triplet repeat expansion and d(CGG.CCG) n
      methylation/demethylation.

PMID- 9171075
TI  - Fractionation, phosphorylation and ligation on oligonucleotide microchips to
      enhance sequencing by hybridization.
AB  - Oligonucleotide microchips are manufactured by immobilizing presynthesized
      oligonucleotides within 0.1 x 0.1 x 0.02 mm or 1 x 1 x 0.02 mm polyacrylamide gel
      pads arranged on the surface of a microscope slide. The gel pads are separated
      from each other by hydrophobic glass spacers and serve as a kind of 'microtest
      tube' of 200 pl or 20 nl volume, respectively. Fractionation of single-stranded
      DNAs is carried out by their hybridization with chip pads containing immobilized
      10mers. DNA extracted separately from each pad is transferred onto a sequencing
      chip and analyzed thereon. The chip, containing a set of 10mers, was
      enzymatically phosphorylated, then hybridized with DNA and ligated in a site
      directed manner with a contiguously stacked 5mer. Several cycles of successive
      hybridization-ligation of the chip-bound 10mers with different contiguously
      stacked 5mers and hybridized with DNA were carried out to sequence DNA containing
      tetranucleotide repeats. Combined use of these techniques show significant
      promise for sequence comparison of homologous regions in different genomes and
      for sequence analysis of comparatively long DNA fragments or DNA containing
      internal repeats.

PMID- 9171076
TI  - A new technique for the characterization of long-range tertiary contacts in large
      RNA molecules: insertion of a photolabel at a selected position in 16S rRNA
      within the Escherichia coli ribosome.
AB  - A new approach for inserting a photo-label at a selected position within the long
      ribosomal RNA molecules has been developed. The Escherichia coli 16S rRNA was
      cleaved at a single internucleotide bond, 1141-1142, with RNase H in the presence
      of a complementary chimeric oligonucleotide. 4-Thiouridine 5', 3'-diphosphate was
      ligated to the 3'-end of the 5'fragment at the cleavage site with T4 RNA ligase.
      The 16S rRNA fragments containing this added photo-reactive nucleotide were
      assembled together with total 30S ribosomal proteins into small ribosomal
      subunits. The ability of such 30S particles containing fragmented rRNA to form
      70S ribosomes has been demonstrated previously. Crosslinks were induced within
      the 30S subunits by mild UV irradiation. The sites of crosslinking within the 16S
      rRNA were then analyzed using RNase H digestion and reverse transcription. Two
      crosslinks from the thio-nucleotide attached to nt C1141 of 16S rRNA were
      observed, namely to nt U1295 and G1272. These results are in agreement with the
      established proximity of helix 39 and 41 in the 3D structure of the 30S ribosomal
      subunit, as shown by other intra RNA crosslinking data. These data furthermore
      allow us to refine the structural arrangement of helices 41 and 39 relative to
      one another.

PMID- 9171077
TI  - NonO enhances the association of many DNA-binding proteins to their targets.
AB  - NonO is an unusual nucleic acid binding protein not only in that it binds both
      DNA and RNA but that it does so via functionally separable domains. Here we
      document that NonO enhances the binding of some (E47, OTF-1 and OTF-2) but not
      all (PEA3) conventional sequence-specific transcription factors to their
      recognition sites in artificial substrates as well as in an immunoglobulin
      VHpromoter. We also show that NonO induces the binding of the Ku complex to DNA
      ends. Ku has no known DNA sequence specificity. These enhancement of binding
      effects are NonO concentration dependent. Using the E box activity of E47 as a
      model, kinetic studies demonstrate that the association rate of the protein-DNA
      complex increases in the presence of NonO while the dissociation rate remains the
      same, thereby increasing the sum total of the interaction. Oligo competition
      experiments indicate that NonO does not contact the target DNA in order to
      enhance the binding activity of DNA binding proteins. Rather, methylation
      interference analysis reveals that the induced E47 binding-activity has the same
      DNA-binding sequence specificity as the normal binding. This result suggests that
      one of the effects of NonO is to induce a true protein-DNA interaction. In this
      way, it might be possible for NonO to play a crucial role in gene regulation.

PMID- 9171079
TI  - BstAPI, an ApaBI isoschizomer, cleaves DNA at 5'-GCANNNN NTGC-3'.
AB  - Cleavage positions of Bst API, a new restriction endonuclease (ENase) that
      recognizes palindromic interrupted DNA sequence, have been determined.
      Recognition sequences and cleavage sites comparison shows that Bst API shares
      similarity with a number of type II restriction enzymes.

PMID- 9171078
TI  - Activation of enhancer elements by the homeobox gene Cdx2 is cell line specific.
AB  - Cdx2 is a caudal-related homeodomain transcription factor that is expressed in
      complex patterns during mouse development and at high levels in the intestinal
      epithelium of adult mice. Cdx2 activates transcription of intestinal gene
      promoters containing specific binding sites. Moreover, Cdx2 has been shown to
      induce intestinal differentiation in cell lines. In this study, we show that Cdx2
      is able to bind to two well defined enhancer elements in the HoxC8 gene. We then
      demonstrate that Cdx2 is able to activate transcription of heterologous promoters
      when its DNA binding element is placed in an enhancer context. Furthermore, the
      ability to activate enhancer elements is cell-line dependent. When the Cdx2
      activation domain was linked to the Gal4 DNA binding domain, the chimeric protein
      was able to activate Gal4 enhancer constructs in an intestinal cell line, but was
      unable to activate transcription in NIH3T3 cells. These data suggest that there
      are cell-specific factors that allow the Cdx2 activation domain to function in
      the activation of enhancer elements. We hypothesize that either a co-activator
      protein or differential phosphorylation of the activation domain may be the
      mechanism for intestinal cell line-specific function of Cdx2 and possibly in
      other tissues in early development.

PMID- 9171080
TI  - A three-dimensional working model for a guide RNA from Trypanosoma brucei.
AB  - RNA editing in protozoan parasites is a mitochondrial RNA processing reaction in
      which exclusively uridylate residues are inserted into, and less frequently
      deleted from, pre-mRNAs. Molecules central to the process are so-called guide
      RNAs (gRNAs) which function as templates in the reaction. For a detailed
      molecular understanding of the mechanism of the editing process knowledge of
      structural features of gRNAs will be essential. Here we report on a computer
      assisted molecular modelling approach to construct the first three-dimensional
      gRNA model for gND7-506, a ND7-specific gRNA from Trypanosoma brucei. The
      modelling process relied on chemical modification and enzymatic probing data and
      was validated by in vitro mutagenesis experiments. The model predicts a
      reasonably compact structure, where two stem/loop secondary structure elements
      are brought into close proximity by a triple A tertiary interaction, forming a
      core element within the centre of the molecule. The model further suggests that
      the surface of the gRNA is primarily made up of the sugar-phoshate backbone. On
      the basis of the model, footprinting experiments of gND7-506 in a complex with
      the gRNA binding protein gBP21 could successfully be interpreted and provide a
      first picture for the assembly of gRNAs within a ribonucleoprotein complex.

PMID- 9171081
TI  - Cloning and characterization of a cDNA encoding a bacteriophage-type RNA
      polymerase from the higher plant Chenopodium album.
AB  - We have cloned a full-length cDNA from the higher plant Chenopodium album coding
      for a single subunit bacteriophage-type RNA polymerase. The cDNA isolated from an
      actively growing cell suspension culture recognized a 3.8 kb transcript on
      Northern blots. The open reading frame comprises 987 amino acids with a predicted
      molecular mass of 112 kDa. A comparison of the protein sequence with those of the
      two known fungal mitochondrial RNA polymerases, from Saccharomyces cerevisiae and
      Neurospora crassa , reveals extensive homology between the three enzymes. with
      complete conservation of all catalytically essential amino acids. The putative
      mitochondrial RNA polymerase from C.album , as well as homologous sequences from
      rice and barley, which have been partially cloned, lack two catalytically non
      essential regions of up to 176 amino acids near the C-terminus present in the two
      fungal mitochondrial RNA polymerases. The extreme N-terminus of the cloned
      C.album RNA polymerase displays features of a potential mitochondrial transit
      sequence. In phylogenetic trees constructed to compare the evolutionary
      relationships between the different single subunit RNA polymerases the C.album
      sequence forms a subgroup together with the S.cerevisiae and the N.crassa
      mitochondrial RNA polymerases, well separating from both bacteriophage enzymes
      and plasmid-encoded RNA polymerases found in mitochondria of many fungi and some
      higher plants.

PMID- 9171082
TI  - Transcription and polyadenylation in a short human intergenic region.
AB  - The poly(A) signal of the human Lamin B2 gene was previously shown to lie 600 bp
      upstream of the cap site of a gene of unknown function (ppv 1). However, using
      RNase protection analysis, we show that ppv 1 has two clusters of multiple
      initiation sites, so that the 5"cap site lies only approximately 280 nt
      downstream of the Lamin B2 poly(A) signal. We analysed nascent transcription
      across this unusually short intergenic region using nuclear run-on analysis of
      both the endogenous locus and of transiently transfected hybrid constructs.
      Surprisingly, transcription of the Lamin B2 gene does not appear to terminate
      prior to any of the mapped ppv 1 start sites, although pausing of the elongating
      polymerase complexes is observed downstream of the Lamin B2 poly(A) signal. We
      suggest that this pausing may be sufficient to protect the downstream gene from
      transcriptional interference. Finally, we have also investigated the sequences
      required for efficient recognition of the Lamin B2 poly(A) signal. We show that
      sequences upstream of the AAUAAA element are required for full activity, which is
      an unusual feature of mammalian poly(A) signals.

PMID- 9171083
TI  - Contrasting effects of single stranded DNA binding protein on the activity of
      uracil DNA glycosylase from Escherichia coli towards different DNA substrates.
AB  - Excision of uracil from tetraloop hairpins and single stranded ('unstructured')
      oligodeoxyribonucleotides by Escherichia coli uracil DNA glycosylase has been
      investigated. We show that, compared with a single stranded reference substrate,
      uracil from the first, second, third and the fourth positions of the loops is
      excised with highly variable efficiencies of 3.21, 0.37, 5.9 and 66.8%,
      respectively. More importantly, inclusion of E.coli single stranded DNA binding
      protein (SSB) in the reactions resulted in approximately 7-140-fold increase in
      the efficiency of uracil excision from the first, second or the third position in
      the loop but showed no significant effect on its excision from the fourth
      position. In contrast, the presence of SSB decreased uracil excision from the
      single stranded ('unstructured') substrates approximately 2-3-fold. The kinetic
      studies show that the increased efficiency of uracil release from the first,
      second and the third positions of the tetraloops is due to a combination of both
      the improved substrate binding and a large increase in the catalytic rates. On
      the other hand, the decreased efficiency of uracil release from the single
      stranded substrates ('unstructured') is mostly due to the lowering of the
      catalytic rates. Chemical probing with KMnO4showed that the presence of SSB
      resulted in the reduction of cleavage of the nucleotides in the vicinity of dUMP
      residue in single stranded substrates but their increased susceptibility in the
      hairpin substrates. We discuss these results to propose that excision of uracil
      from DNA-SSB complexes by uracil DNA glycosylase involves base flipping. The use
      of SSB in the various applications of uracil DNA glycosylase is also discussed.

PMID- 9171086
TI  - The sequence specificity of alkylation for a series of benzoic acid mustard and
      imidazole-containing distamycin analogues: the importance of local sequence
      conformation.
AB  - The covalent sequence specificity of a series of nitrogen mustard and imidazole
      containing analogues of distamycin was determined using modified sequencing
      techniques. The analogues tether benzoic acid mustard (BAM) and possess either
      one, two or three imidazole units. Examination of the alkylation specificity
      revealed that BAM produced guanine-N7 lesions in a pattern similar to
      conventional nitrogen mustards. The monoimidazole-BAM conjugate also produced
      guanine-N7 alkylation in a similar pattern to BAM, but at a 100-fold lower dose.
      The diimidazole and triimidazole conjugates did not produce detectable guanine-N7
      alkylation but only alkylated at selected sites in the minor groove.
      Unexpectedly, the alkylation specificity at equivalent doses was nearly identical
      to that found for the previously reported pyrrole-BAM conjugates. The consensus
      sequence, 5'-TTTTGPuwas strongly alkylated by the triimidazole conjugate in
      preference to other similar sites including three occurrences of 5'-TTTTAA.
      Footprinting studies were carried out to examine the non-covalent DNA binding
      interactions. These studies revealed that the tripyrrole- BAM conjugate bound non
      covalently to the same AT-rich sites as distamycin. In contrast, whereas the
      Im3lexitropsin bound non-covalently to GC-rich sequences, the triimidazole-BAM
      conjugate did not detectably footprint to either GC- or AT-rich regions at
      equivalent doses. The results indicate that the alkylation event is not solely
      dictated by the non-covalent binding and might be influenced by a unique sequence
      dependent conformational feature of the consensus sequence 5'-TTTTGPu.

PMID- 9171084
TI  - The murine IgM secretory poly(A) site contains dual upstream and downstream
      elements which affect polyadenylation.
AB  - Regulation of polyadenylation efficiency at the secretory poly(A) site plays an
      essential role in gene expression at the immunoglobulin (IgM) locus. At this
      poly(A) site the consensus AAUAAA hexanucleotide sequence is embedded in an
      extended AU-rich region and there are two downstream GU-rich regions which are
      suboptimally placed. As these sequences are involved in formation of the
      polyadenylation pre-initiation complex, we examined their function in vivo and in
      vitro . We show that the upstream AU-rich region can function in the absence of
      the consensus hexanucleotide sequence both in vivo and in vitro and that both GU
      rich regions are necessary for full polyadenylation activity in vivo and for
      formation of polyadenylation-specific complexes in vitro . Sequence comparisons
      reveal that: (i) the dual structure is distinct for the IgM secretory poly(A)
      site compared with other immunoglobulin isotype secretory poly(A) sites; (ii) the
      presence of an AU-rich region close to the consensus hexanucleotide is
      evolutionarily conserved for IgM secretory poly(A) sites. We propose that the
      dual structure of the IgM secretory poly(A) site provides a flexibility to
      accommodate changes in polyadenylation complex components during regulation of
      polyadenylation efficiency.

PMID- 9171085
TI  - Synthesis and evaluation of oligodeoxyribonucleotides containing an
      aryl(trifluoromethyl)diazirine moiety as the cross-linking probe: photoaffinity
      labeling of mammalian DNA polymerase beta.
AB  - Photolabile 2'-deoxy- E -5-[4-(3-trifluoromethyl-3 H-diazirin-3-yl)styryl]uridine
      and its protected phosphoramidite derivatives have been synthesized and
      introduced into DNA oligomers through solid-phase DNA synthesis. The
      (trifluoromethyldiazirinyl)stylyl moiety of this nucleoside was found to be
      sufficiently stable for automated DNA synthesis. In addition, this moiety was
      found to be stable at 60 degrees C in aqueous solution under the annealing
      conditions for duplex formation with complementary strands, since >95% of the
      photolabile nucleoside remained after heating for 1 h. The oligo(dT) 15mer analog
      bearing the photolabile residue was activated/decomposed by near-UV irradiation.
      In photoaffinity cross-linking experiments with recombinant rat DNA
      polymerasebeta, constituted from a 40 kDa polypeptide, using oligo(dT) 15mer
      analogs bearing the photolabile residue near the 3'-terminus, a covalently bound
      complex of 45 kDa was obtained in the presence of complementary templates. Thus
      it was demonstrated that our method for synthesis of photolabile
      oligodeoxyribonucleotides may be useful for studies of DNA-related enzymes and
      DNA binding proteins.

PMID- 9171087
TI  - Differential developmental expression of the rep B and rep D xeroderma
      pigmentosum related DNA helicase genes from Dictyostelium discoideum.
AB  - DNA helicases are essential to many cellular processes including recombination,
      replication and transcription, and some helicases function in multiple processes.
      The helicases encoded by the Xeroderma pigmentosum (XP) B and D genes function in
      both nucleotide excision repair and transcription initiation. Mutations that
      affect the repair function of these proteins result in XP while mutations
      affecting transcription result in neurological and developmental abnormalities,
      although the underlying molecular and cellular basis for these phenotypes is not
      well understood. To better understand the developmental roles of these genes, we
      have now identified and characterized the rep B and rep D genes from the cellular
      slime mold Dictyostelium discoideum . Both genes encode DNA helicases of the SF2
      superfamily of helicases. The rep D gene contains no introns and the rep B gene
      contains only one intron, which makes their genomic structures dramatically
      different from the corresponding genes in mammals and fish. However the predicted
      Dictyostelium proteins share high homology with the human XPB and XPD proteins.
      The single copy of the rep B and D genes map to chromosomes 3 and 1,
      respectively. The expression of rep B and D (and the previously isolated rep E)
      genes during multicellular development was examined, and it was determined that
      each rep gene has a unique pattern of expression, consistent with the idea that
      they have specific roles in development. The pattern and extent of expression of
      these genes was not affected by the growth history of the cells, implying that
      the expression of these genes is tightly regulated by the developmental program.
      The expression of the rep genes is a very early step in development and may well
      represent a key event in the initiation of development in this organism.

PMID- 9171088
TI  - Demethylation of DNA by purified chick embryo 5-methylcytosine-DNA glycosylase
      requires both protein and RNA.
AB  - We have previously purified and characterized a 5-methylcytosine (5-MeC)-DNA
      glycosylase from 12 day old chick embryos [Jost,J.P. et al. (1995) J. Biol. Chem.
      270, 9734-9739]. The activity of the purified enzyme is abolished upon treatment
      with proteinase K and ribonuclease A. RNA copurifies with 5-MeC-DNA glycosylase
      activity throughout all chromatographic steps and preparative gel
      electrophoresis. RNA with a length of approximately 300-500 nucleotides was
      isolated from the gel purified enzyme. Upon extensive treatment with proteinase
      K, the gel eluted and labeled RNA did not show any significant change in
      molecular mass. The purified RNA incubated alone or in the presence of Mg2+and
      deoxyribonucleotide phosphates had no 5-MeC-DNA glycosylase or demethylating
      activities. However, activity of 5-MeC-DNA glycosylase could be restored when the
      purified RNA was incubated with the inactive protein, free of RNA.

PMID- 9171089
TI  - Introduction of precise alterations into the mouse genome with high efficiency by
      stable tag-exchange gene targeting: implications for gene targeting in ES cells.
AB  - The efficiency of tag-and-exchange gene targeting approaches for the introduction
      of precise genomic modifications is compromised by high levels of non-homologous
      recombinants which survive selection due to loss of tag gene expression, often by
      physical loss of the tag gene. We describe a modified approach, termed stable tag
      exchange, which incorporates an additional positive selection (stability)
      cassette to circumvent this limitation. HPRT (tag) and neo (stability) cassettes,
      separated by 4.9 kb of homologous DNA, were introduced efficiently into the LIF
      locus of ES cells. The tag cassette was substituted for abeta-galactosidase gene
      in exchange step targeting. Direct comparison of the tag-and-exchange and stable
      tag-exchange approaches indicated respective targeting efficiencies of 21% and
      88%. The increased stable tag-exchange targeting efficiency resulted from
      elimination of >75% of background lines which survived tag-and-exchange selection
      due to physical loss of the tag gene. These resulted from reversion of the tagged
      allele to wild-type which is therefore a major contributor to tag-and-exchange
      targeting background. Our results extend the application of gene targeting by
      demonstrating a rationale for single-step integration of multiple regions of
      extended non-homology, and providing an efficient system for the repeated
      introduction of precise alterations into the mammalian genome.

PMID- 9171090
TI  - Expression of herpes virus thymidine kinase in Neurospora crassa.
AB  - The expression of thymidine kinase in fungi, which normally lack this enzyme,
      will greatly aid the study of DNA metabolism and provide useful drug-sensitive
      phenotypes. The herpes simplex virus type-1 thymidine kinase gene ( tk ) was
      expressed in Neurospora crassa. tk was expressed as a fusion to N.crassa arg-2
      regulatory sequences and as a hygromycin phosphotransferase-thymidine kinase
      fusion gene under the control of cytomegalovirus and SV40 sequences. Only strains
      containing tk showed thymidine kinase enzyme activity. In strains containing the
      arg-2 - tk gene, both the level of enzyme activity and the level of mRNA were
      reduced by growth in arginine medium, consistent with control through arg-2
      regulatory sequences. Expression of thymidine kinase in N.crassa facilitated
      radioactive labeling of replicating DNA following addition of [3H]thymidine or
      [14C]thymidine to the growth medium. Thymidine labeling of DNA enabled
      demonstration that hydroxyurea can be used to block replication and synchronize
      the N.crassa mitotic cycle. Strains expressing thymidine kinase were also more
      sensitive than strains lacking thymidine kinase to anticancer and antiviral
      nucleoside drugs that are activated by thymidine kinase, including 5-fluoro-2'
      deoxyuridine, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouridine and
      trifluorothymidine. Finally, expression of thymidine kinase in N. crassa enabled
      incorporation of bromodeoxyuridine into DNA at levels sufficient to separate
      newly replicated DNA from old DNA using equilibrium centrifugation.

PMID- 9171091
TI  - Effects of natural and synthetic polyamines on the conformation of an
      oligodeoxyribonucleotide with the estrogen response element.
AB  - We studied the effects of natural and synthetic polyamines on the conformation of
      an oligodeoxyribonucleotide (ODN1) harboring the estrogen response element (ERE)
      by circular dichroism (CD) spectroscopy and polyacrylamide gel electrophoresis.
      Putrescine and spermidine had no marked effect on the CD spectrum of ODN1. In
      contrast, spermine provoked and stabilized two characteristic changes in the CD
      spectrum. The first change was indicated by an increase in the intensity of the
      CD band at 280 nm at 0.5 mM spermine in Tris-HCl buffer containing 50 mM NaCl.
      This change appears to be related to changes in base tilt and conformational
      alterations similar to A-DNA. At 1-2 mM spermine, the CD spectrum was
      characterized by a loss of positive bands at 220 and 270 nm. This change might
      have contributions from polyamine-induced condensation/aggregation of DNA.
      Spectral measurements were also conducted in Tris-HCl buffer containing 150 mM
      NaCl to minimize contributions from condensation and aggregation of ODN1. Under
      these conditions, CD spectral changes were retained by (ODN1), although the
      magnitude of the change was diminished. In contrast, a control
      oligdeoxyribonucleotide (ODN2) having similar base composition did not show any
      significant change in the CD spectrum in the presence of 150 mM NaCl and 2 mM
      spermine. The changes in the CD spectrum of ODN1 were highly sensitive to
      polyamine structure, as evidenced by experiments using spermine analogs with
      altered number of -CH2- groups separating the amino and imino groups.
      Electrophoretic mobility shift analysis further showed ODN1 stabilization by
      spermine and its analogs. These data demonstrate the ability of an ODN containing
      ERE to undergo conformational transitions in the presence of polyamines and
      suggest a possible mechanism for polyamine-mediated alterations in the
      interaction of estrogen receptor with ERE.

PMID- 9171092
TI  - Chloroplast endoribonuclease p54 involved in RNA 3'-end processing is regulated
      by phosphorylation and redox state.
AB  - Chloroplast RNA-binding protein p54 is an endoribonuclease required for 3'end
      processing of plastid precursor transcripts. We find that purified p54 can serve
      as a phosphate acceptor for protein kinases in vitro. Both the processing and RNA
      binding activities of p54 are enhanced by phosphorylation and decreased by
      dephosphorylation. In addition, the enzyme is activated by the oxidized form of
      glutathione and inhibited by the reduced form, whereas other redox reagents that
      were tested showed no effect. Kinase treatment of p54 prior to oxidation by
      glutathione resulted in highest levels of activation, suggesting that
      phosphorylation and redox state act together to control p54 activity in vitro and
      possibly also in vivo.

PMID- 9171093
TI  - Novel pattern of DNA methylation in Neurospora crassa transgenic for the foreign
      gene hph.
AB  - It has previously been reported that multiple copies of the hph gene integrated
      into the genome of Neurospora crassa are methylated at Hpa II sites (CCGG) during
      the vegetative life cycle of the fungus, while hph genes integrated as single
      copies are not methylated. Furthermore, methylation is correlated with silencing
      of the gene. We report here the methylation state of cytosine residues of the
      major part of the promoter region of the hph gene integrated into the genome of
      the multiple copy strain HTA5.7 during the vegetative stage of the life cycle.
      Cytosine methylation is sequence dependent, but the sequence specificity is
      complex and is different from the sequence specificity known for mammals and
      plants (CpG and CpNpG). The pattern of DNA methylation reported here is very
      different from that measured after meiosis in Neurospora or in Ascobulus . After
      the sexual cycle in those two fungi all the cytosines of multiple stretches of
      DNA are heavily methylated. This indicates that the still unknown
      methyltransferase in Neurospora has a different specificity in the sexual and the
      vegetative stages of the life cycle or that there are different
      methyltransferases. The pattern of methylation reported here is also different
      from the pattern of cytosine methylation of transgenes of Petunia , the only
      pattern published until now in plants that has DNA methylation at cytosines which
      are not in the canonical sequences CpG and CpNpG.

PMID- 9171094
TI  - Identification of proteins binding specifically to the 3'-untranslated region of
      granulocyte/macrophage-colony stimulating factor mRNA.
AB  - The 3'-untranslated region of granulocyte/macrophage colony-stimulating factor
      (GM-CSF) mRNA contributes to the post-transcriptional regulation of gene
      expression. Degradation is partly mediated by adenosine- uridine-rich sequence
      elements (ARE), which serve as binding sites for specific proteins. Stabilization
      of RNA by phytohemagglutinin and concanavalin A treatment is dependent on
      regulatory sequence elements upstream of ARE. We have performed northwestern blot
      and filter binding assays using cell extracts and RNA sequences containing or
      lacking ARE. Murine and human T cell extracts (EL-4 and Jurkat) yielded two
      specific proteins of 93 and 94 kDa, respectively, that were binding to sequences
      upstream of ARE. Within this region, the human and murine RNA do not share any
      obvious sequence identity, yet both are target sites for the binding proteins.
      The smallest RNA fragments protected by the proteins from RNase A digestion, were
      44 in the murine, and 38 ribonucleotides long in the human sequence. The binding
      activity of the 94 kDa protein derived from human Jurkat cells could be enhanced
      by phytohemagglutinin. The interaction with regulatory mRNA sequences and the
      responsiveness to phytohemagglutinin suggests that the proteins are involved in
      controlling GM-CSF mRNA turnover.

PMID- 9171095
TI  - Estrogen receptor impairs interleukin-6 expression by preventing protein binding
      on the NF-kappaB site.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine thought to be a key factor in
      post-menopausal osteoporosis, given its ability to induce osteoclast maturation
      and its down regulation by estrogens. We have previously shown that the effects
      of TNFalphaand estradiol on the human IL-6 promoter were dependent on a region of
      the promoter containing a C/EBP site and a NF-kappaB site. To define the
      molecular mode of action of estrogens, we performed gel shift assays with this
      DNA fragment as a probe, and nuclear extracts from TNFalpha-induced HeLa, MCF7
      and Saos2 cells. Several induced complexes specifically bound the probe. The use
      of various competitor DNA suggested that most of the complexes detected contained
      NF-kappaB factors, and that C/EBP site binding factors were important for the
      overall binding to the probe. Addition of in vitro translated human estrogen
      receptor (hER) impaired the binding of three complexes in HeLa cells and two
      complexes in MCF7 and Saos2 cells. Competition experiments suggested that the NF
      kappaB site was necessary for the effect of hER. The use of antisera against NF
      kappaB and C/EBP proteins showed that the target complexes of hER contained the c
      rel proto-oncogene product and to a lesser extent, the RelA protein. Taken
      together, these data show that hER impairs TNFalphainduction of IL-6 by
      preventing c-rel and, to a lesser extent, RelA proteins binding to the NF-kappaB
      site of the IL-6 promoter.

PMID- 9171096
TI  - Avoidance of palindromic words in bacterial and archaeal genomes: a close
      connection with restriction enzymes.
AB  - Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a
      statistically significant level in the genomes of several bacteria, including the
      completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in
      the complete genome of the archaeon Methanococcus jannaschii. In contrast, there
      is only moderate avoidance of palindromes in the small genome of the bacterium
      Mycoplasma genitalium and no detectable avoidance in the genomes of chloroplasts
      and mitochondria. The sites for type II restriction-modification enzymes detected
      in the given species tend to be among the most avoided palindromes in a
      particular genome, indicating a direct connection between the avoidance of short
      oligonucleotide words and restriction-modification systems with the respective
      specificity. Palindromes corresponding to sites for restriction enzymes from
      other species are also avoided, albeit less significantly, suggesting that in the
      course of evolution bacterial DNA has been exposed to a wide spectrum of
      restriction enzymes, probably as the result of lateral transfer mediated by
      mobile genetic elements, such as plasmids and prophages. Palindromic words appear
      to accumulate in DNA once it becomes isolated from restriction-modification
      systems, as demonstrated by the case of organellar genomes. By combining these
      observations with protein sequence analysis, we show that the most avoided 4
      palindrome and the most avoided 6-palindrome in the archaeon M.jannaschii are
      likely to be recognition sites for two novel restriction-modification systems.

PMID- 9171097
TI  - Human transcription factors IIIC2 , IIIC1 and a novel component IIIC0 fulfil
      different aspects of DNA binding to various pol III genes.
AB  - Human transcription factor IIIC2 interacts with the TFIIIA-5S DNA complex and
      forms a ternary TFIIIA/IIIC2-5S DNA complex. Formation of this complex does not
      preclude simultaneous binding of TFIIIC2to the B-box sequence of a second
      template. This suggests that the domain(s) or subunit(s) required for indirect
      recognition of the 5S promoter by TFIIIC2 are different from those necessary for
      direct binding of TFIIIC2 to B-box-containing pol III promoters. Whereas TFIIIC2
      is only required for transcription of the 'classical' pol III genes, TFIIIC1 is
      generally required for transcription of all pol III genes, including that of the
      U6 gene. The activity of TFIIIC1 strongly enhances specific binding of basal pol
      III factors TFIIIA, TFIIIC2 and the PSE binding protein (PBP) to their cognate
      promoter elements and it acts independently of the corresponding termination
      regions. Moreover, we characterize an activity, TFIIIC0, purified from
      phosphocellulose fraction C, which shows strong DNase I protection of the
      termination region of several pol III genes and which is functionally and
      chromatographically distinct from TFIIIC1 and TFIIIC2.

PMID- 9171098
TI  - Deletion endpoint allele-specificity in the developmentally regulated elimination
      of an internal sequence (IES) in Paramecium.
AB  - Ciliated protozoa undergo thousands of site-specific DNA deletion events during
      the programmed development of micronuclear genomes to macronuclear genomes. Two
      deletion elements, W1 and W2, were identified in the Paramecium primaurelia wild
      type 156 strain. Here, we report the characterization of both elements in wild
      type strain 168 and show that they display variant deletion patterns when
      compared with those of strain 156. The W1 ( 168 ) element is defective for
      deletion. The W2 ( 168 ) element is excised utilizing two alternative boundaries
      on one side, both are different from the boundary utilized to excise the W2156
      element. By crossing the 156 and 168 strains, we demonstrate that the definition
      of all deletion endpoints are each controlled by cis -acting determinant(s)
      rather than by strain-specific trans-acting factor(s). Sequence comparison of all
      deleted DNA segments indicates that the 5'-TA-3'terminal sequence is strictly
      required at their ends. Furthermore the identity of the first eight base pairs of
      these ends to a previously established consensus sequence correlates with the
      frequency of the corresponding deletion events. Our data implies the existence of
      an adaptive convergent evolution of these Paramecium deleted DNA segment end
      sequences.

PMID- 9171099
TI  - Comprehensive, rapid and sensitive detection of sequence variants of human
      mitochondrial tRNA genes.
AB  - In the present study, a comprehensive, rapid and sensitive method for screening
      sequence variation of the human mitochondrial tRNA genes has been developed. For
      this purpose, the denaturing gradient gel electrophoresis (DGGE) technique has
      been appropriately modified for simultaneous mutation analysis of a large number
      of samples and adapted so as to circumvent the problems caused by the anomalous
      electrophoretic behavior of DNA fragments encoding tRNA genes. Eighteen segments
      of mitochondrial DNA (mtDNA), each containing a single uniform melting domain,
      were selected to cover all tRNA-encoding regions using the computer program
      MELT94. All 18 segments were simultaneously analyzed by electrophoresis through a
      single broad range denaturing gradient gel under rigorously defined conditions,
      which prevent band broadening and other migration abnormalities from interfering
      with detection of sequence variants. All base substitutions tested, which include
      six natural mutations and 14 artificially introduced ones, have been detected
      successfully in the present study. Several types of evidence strongly suggest
      that the anomalous behavior in DGGE of tRNA gene-containing mtDNA fragments
      reflects their tendency to form temporary or stable alternative secondary
      structures under semi-denaturing conditions. The high sensitivity of the method,
      which can detect as low as 10% of mutant mtDNA visually, makes it valuable for
      the analysis of heteroplasmic mutations.

PMID- 9171100
TI  - Variations of the C2H2 zinc finger motif in the yeast genome and classification
      of yeast zinc finger proteins.
AB  - The PROSITE pattern Zinc_Finger_C2H2 was extended to permit the detection of all
      C2H2 zinc fingers and their parent proteins in the recently completed sequence of
      the yeast genome. Additionally, a new computer program was written that extracts
      other zinc binding motifs (non C2H2 'fingers'), overlapping with the classical
      zinc finger pattern, from the found set of yeast C2H2 fingers. The complete and
      correct detection of all fingers is a prerequisite for the classification of the
      yeast zinc finger proteins in functional terms. The detected 53 yeast C2H2 zinc
      finger proteins do not contain finger clusters with 10 or more repeats, as is
      frequently found in higher eukaryotes. Only three proteins contain four or more
      fingers in a cluster. Moreover, nearly all 27 yeast proteins with tandem arrays
      of two or three finger domains can be classified into nine subgroups with high
      sequence conservation in their finger clusters, in particular of their DNA
      recognition helices. These results and application of the recently elaborated
      finger/DNA recognition rules suggest that the yeast proteins belonging to the
      same subgroup may recognize identical or very similar DNA sites.

PMID- 9171101
TI  - The chick type III collagen gene contains two promoters that are preferentially
      expressed in different cell types and are separated by over 20 kb of DNA
      containing 23 exons.
AB  - Type III collagen is present in prechondrogenic mesenchyme, but not in cartilages
      formed during endochondral ossification. However, cultured chick chondrocytes
      contain an unusual transcript of the type III collagen gene in which exons 1-23
      are replaced with a previously undescribed exon, 23A; this alternative transcript
      does not encode type III collagen. This observation suggested that, although
      production of type III collagen mRNA is repressed in chondrocytes, transcription
      of the type III collagen gene may continue from an alternative promoter. To test
      this prediction, we isolated and characterized both the upstream and internal
      promoters of this gene and tested their ability to direct transcription in
      chondrocytes and skin fibroblasts. The upstream promoter is active in
      fibroblasts, but inactive in chondrocytes, indicating that repression of type III
      collagen synthesis during chondrogenesis is transcriptionally mediated.
      Additionally, sequences in intron 23, preceding exon 23A, function as a highly
      active promoter in chondrocytes; transcription from this promoter is repressed in
      fibroblasts. Thus transcriptional control of the type III collagen gene is highly
      complex, with two promoters separated by at least 20 kb of DNA that are
      preferentially expressed in different cell types and give rise to RNAs with
      different structures and functions.

PMID- 9171102
TI  - Crosslinking of progesterone receptor to DNA using tuneable nanosecond,
      picosecond and femtosecond UV laser pulses.
AB  - UV laser crosslinking is a potentially powerful tool to investigate transient DNA
      protein interactions and binding kinetics in intact cells. As the processes
      underlying UV laser crosslinking are not fully understood, we have performed a
      study of the influence of laser pulses with different physical parameters on
      crosslinking of the progesterone receptor to an oligonucleotide containing a
      hormone-responsive element. We also studied the influence of the various
      parameters on the amount of laser-irradiated DNA that can be correctly primer
      extended as an operational measurement of DNA integrity. A strong influence of
      pulse intensity and pulse length on the crosslink yield was found, likely due to
      a change in the 'two photon' processes responsible for crosslinking. The highest
      efficiency of protein crosslinking to DNA was achieved with femtosecond pulses
      and should be sufficient to enable use of this technique for in vivo studies.

PMID- 9171103
TI  - Analysis of the human TATA binding protein promoter and identification of an ets
      site critical for activity.
AB  - The TATA binding protein (TBP) is a general transcription factor required for
      initiation by all three eukaryotic nuclear RNA polymerases. Little is known about
      how TBP gene expression is regulated. To identify sequence elements and proteins
      contributing to human TBP (hTBP) gene transcription, we have characterized the
      promoter in two human cell lines. Multiple 5'-ends of TBP mRNA mapped throughout
      a 111 bp region immediately upstream of a previously reported hTBP cDNA. Upon
      transient transfection into cells, the hTBP 5'-flanking region was shown to
      contain a fairly active promoter. The cis -acting elements responsible for this
      promoter activity in Namalwa and HeLa cells were localized in vivo by deletion
      analysis. The minimal promoter defined from these experiments was a 54 bp region
      that encompassed all but one minor start site and contained a functional Ets
      protein consensus binding site, which was shown to be required for promoter
      activity in both cell lines. The importance of other potential elements to
      promoter activity was found to differ between the two cell lines. Consistent with
      that finding, different complexes were formed on promoter-containing DNA
      fragments upon incubation with nuclear extracts prepared from the different
      cells.

PMID- 9171104
TI  - 3'-phosphodiesterase activity of human apurinic/apyrimidinic endonuclease at DNA
      double-strand break ends.
AB  - In order to assess the possible role of human apurinic/apyrimidinic endonuclease
      (Ape) in double-strand break repair, the substrate specificity of this enzyme was
      investigated using short DNA duplexes and partial duplexes, each having a single
      3'-phosphoglycolate terminus. Phosphoglycolate removal by Ape was detected as a
      shift in mobility of 5'-end-labeled DNA strands on polyacrylamide sequencing
      gels, and was quantified by phosphorimaging. Recombinant Ape efficiently removed
      phosphoglycolates from the 3'-terminus of an internal 1 base gap in a 38mer
      duplex, but acted more slowly on 3'-phosphoglycolates at a 19 base-recessed 3'
      terminus, at an internal nick with no missing bases, and at a double-strand break
      end with either blunt or 2 base-recessed 3'-termini. There was no detectable
      activity of Ape toward 3'-phosphoglycolates on 1 or 2 base protruding single
      stranded 3'-overhangs. The results suggest that both a single-base internal gap,
      and duplex DNA on each side of the gap are important binding/recognition
      determinants for Ape. While Ape may play a role in repair of terminally blocked
      double-strand breaks, there must also be additional factors involved in removal
      of at least some damaged 3'-termini, particularly those on 3'-overhangs.

PMID- 9171105
TI  - Hepatocyte nuclear factor-4 prevents silencing of hepatocyte nuclear factor-1
      expression in hepatoma x fibroblast cell hybrids.
AB  - Hepatocyte nuclear factors-1alpha (HNF1alpha) and -4 (HNF4) are components of a
      liver-enriched transcription activation pathway which is thought to play a
      critical role in hepatocyte-specific gene expression, including activation of
      alpha1-antitrypsin gene expression. HNF1alpha, HNF4 and alpha1-antitrypsin
      (alpha1AT) genes are extinguished in hepatoma/fibroblast somatic cell hybrids,
      suggesting that fibroblasts contain a repressor-like activity. To determine the
      molecular basis for silencing of these genes in cell hybrids, ectopic expression
      of HNF1alpha and HNF4 was used. Results show that constitutive expression of HNF4
      prevents extinction of HNF1alpha gene expression in hepatoma/fibroblast hybrids.
      In contrast, forced HNF1alpha expression failed to prevent extinction of the HNF4
      locus in cell hybrids. Likewise, the alpha1AT gene remained silent in the
      presence of both HNF1alpha and HNF4. These results suggest that extinction of
      HNF1alpha is a simple lack-of-activation phenotype, whereas extinction of HNF4
      andalpha1AT loci is more complex, perhaps involving negative regulation.

PMID- 9171106
TI  - Multiple regions of p45 NF-E2 are required for beta-globin gene expression in
      erythroid cells.
AB  - Regulated expression of genes in the beta-globin cluster depends upon sequences
      located between 5 and 20 kb upstream of the epsilon gene, known as the locus
      control region (LCR). beta-Globin expression in murine erythroleukemia (MEL)
      cells depends on NF-E2, a transcription factor which binds to enhancer sequences
      in the LCR. To gain insight into the mechanism of globin gene activation by NF
      E2, an NF-E2 null MEL cell line was used to map regions of NF-E2 required for
      beta-globin expression. Within the transactivation domain, two discrete proline
      rich regions were required for rescue of beta-globin expression. The first was
      located at the N-terminus of NF-E2, while the second was located N-terminal of
      the cap 'n collar (CNC) domain. Other proline-rich sequences were dispensable,
      indicating that proline content per se does not determine NF-E2 activity.
      Mutations within the conserved CNC domain markedly diminished rescue of beta
      globin expression. This domain was required, in addition to the basic leucine
      zipper domain, for DNA binding activity. The requirement for discrete proline
      rich sequences within the transactivation domain suggests that globin gene
      expression in MEL cells depends on specific interactions between NF-E2 and
      downstream effector molecules.

PMID- 9171107
TI  - A closed tube format for amplification and detection of DNA based on energy
      transfer.
AB  - A new method for the direct detection of PCR-amplified DNA in a closed system is
      described. The method is based on the incorporation of energy transfer-labeled
      primers into the amplification product. The PCR primers contain hairpin
      structures on their 5'ends with donor and acceptor moieties located in close
      proximity on the hairpin stem. The primers are designed in such a way that a
      fluorescent signal is generated only when the primers are incorporated into an
      amplification product. A signal to background ratio of 35:1 was obtained using
      the hairpin primers labeled with fluorescein as a donor and 4-(4'
      dimethylaminophenylazo) benzoic acid (DABCYL) as a quencher. The modified hairpin
      primers do not interfere with the activity of DNA polymerase, and both
      thermostable Pfu and Taq polymerase can be used. This method was applied to the
      detection of cDNA for prostate specific antigen. The results demonstrate that the
      fluorescent intensity of the amplified product correlates with the amount of
      incorporated primers, and as few as 10 molecules of the initial template can be
      detected. This technology eliminates the risk of carry-over contamination,
      simplifies the amplification assay and opens up new possibilities for the real
      time quantification of the amplified DNA over an extremely wide dynamic range.

PMID- 9171108
TI  - The class II trans-activator CIITA interacts with the TBP-associated factor
      TAFII32.
AB  - The class II trans- activator (CIITA) is the main transcriptional co-activator
      for the expression of MHC class II proteins. Its N-terminal 125 amino acids
      function as an independent transcriptional activation domain. Analyses of the
      primary amino acid sequence of the activation domain predict the presence of
      three alpha-helices, each with a high proportion of acidic residues. Using site
      directed mutagenesis, we found that two of these predicted alpha-helices are
      required for full transcriptional activation by CIITA. Moreover, a CIITA protein
      in which both functional alpha-helices have been deleted displays a dominant
      negative phenotype. This activation domain of CIITA interacts with the 32 kDa
      subunit of the general transcription complex TFIID, TAFII32. Decreased
      transcriptional activation by N-terminal deletions of CIITA is correlated
      directly with their reduced binding to TAFII32. We conclude that interactions
      between TAFII32 and CIITA are responsible for activation of class II genes.

PMID- 9171109
TI  - Rapid quantitation of methylation differences at specific sites using methylation
      sensitive single nucleotide primer extension (Ms-SNuPE).
AB  - We have developed a rapid quantitative method (Ms-SNuPE) for assessing
      methylation differences at specific CpG sites based on bisulfite treatment of DNA
      followed by single nucleotide primer extension. Genomic DNA was first reacted
      with sodium bisulfite to convert unmethylated cytosine to uracil while leaving 5
      methylcytosine unchanged. Amplification of the desired target sequence was then
      performed using PCR primers specific for bisulfite-converted DNA and the
      resulting product isolated and used as a template for methylation analysis at the
      CpG site(s) of interest. This methylation-sensitive technique has several
      advantages over existing methods used for detection of methylation changes
      because small amounts of DNA can be analyzed including microdissected pathology
      sections and it avoids utilization of restriction enzymes for determining the
      methylation status at CpG sites.

PMID- 9171110
TI  - COBRA: a sensitive and quantitative DNA methylation assay.
AB  - We report here on a quantitative technique called COBRA to determine DNA
      methylation levels at specific gene loci in small amounts of genomic DNA.
      Restriction enzyme digestion is used to reveal methylation-dependent sequence
      differences in PCR products of sodium bisulfite-treated DNA as described
      previously. We show that methylation levels in the original DNA sample are
      represented by the relative amounts of digested and undigested PCR product in a
      linearly quantitative fashion across a wide spectrum of DNA methylation levels.
      In addition, we show that this technique can be reliably applied to DNA obtained
      from microdissected paraffin-embedded tissue samples. COBRA thus combines the
      powerful features of ease of use, quantitative accuracy, and compatibility with
      paraffin sections.

PMID- 9171111
TI  - S1 nuclease hybrid analysis of mitochondrial DNA amplified by long-distance PCR:
      rapid screening for small-scale rearrangements.
AB  - We report on a method suitable for screening large regions (>3 kb) of mtDNA for
      structural changes of <500 bp and their localization. Heteroduplexes consisting
      of a wild-type and a mutant strand are cleaved by S1nuclease when single-stranded
      loops are present due to deletions or duplications/insertions. This strategy was
      successfully applied to screen the muscle mtDNA of 20 patients with mitochondrial
      encephalomyopathies. In three of them, an altered cleavage pattern was observed
      caused by a homoplasmic 9 bp deletion as shown by subsequent mapping and
      sequencing studies.

PMID- 9171112
TI  - Glutathione S-transferase fusion proteins as an affinity reagent for rapid
      isolation of specific sequence directly from genomic DNA.
AB  - We describe a DNA binding assay for isolation of specific sequence(s) recognized
      by protein of interest directly from genomic or cosmid DNA. In our assay, the
      protein is fused to the glutathione-S-transferase and bound to glutathione
      Sepharose beads. Then the immobilized fusion protein can be used to search for
      DNA fragment(s) that interact specifically with the protein of interest. As an
      example of such an approach, we identified and cloned a few prokaryotic oriC
      regions using the initiator DnaA protein fused to the glutathione-S-transferase.

PMID- 9171113
TI  - Efficient Cre-lox linearisation of BACs: applications to physical mapping and
      generation of transgenic animals.
AB  - Due to the size of BAC, PAC and P1 clones, it is often difficult to construct
      detailed restriction maps, with large number of restriction fragments leading to
      ambiguity of mapping data. We report the use of Cre recombinase to linearise and
      asymmetrically introduce label at the unique loxP site of large loxP-containing
      clones. Subsequent partial digestion allows the direct ordering of restriction
      fragments. Additionally, BAC DNA linearised using the Cre-lox system has been
      used successfully to generate transgenic animals.

PMID- 9171114
TI  - Ordered differential display: a simple method for systematic comparison of gene
      expression profiles.
AB  - A method for display of 3'-end restriction fragments of cDNAs is proposed,
      extending the idea reported recently. First, representative pools of such
      fragments are selectively amplified using PCR suppression effect. Then,
      simplified subsets of these fragments suitable for comparison by PAGE are
      amplified by adapter-specific primers extended by two randomly picked bases at
      their 3'ends. By testing all possible combinations of extended primers the whole
      mRNA pool may be systematically investigated. The method was applied to search
      for molecular regional markers of freshwater planarian Dugesia tigrina .

PMID- 9171116
TI  - Complete and partial laparoscopic fundoplication for gastroesophageal reflux
      disease.

PMID- 9171115
TI  - Targeted expression of Cre recombinase to adipose tissue of transgenic mice
      directs adipose-specific excision of loxP-flanked gene segments.
AB  - Functional analysis of mammalian genes relies, in part, on targeted mutations
      generated by homologous recombination in mice. We have developed a strategy for
      adipose-specific inactivation of loxP-floxed gene segments. Transgenic mice have
      been established that express Cre recombinase under the control of the adipose
      specific aP2 enhancer/promoter. Crossing of the aP2/ Cre mice with any loxP
      floxed gene will facilitate its functional analysis in adipose tissue.

PMID- 9171117
TI  - How safe is ERCP to the endoscopist?
AB  - BACKGROUND: Interventional techniques in endoscopy such as endoscopic retrograde
      cholangiopancreatography (ERCP) have greatly increased since laparoscopic
      cholecystectomy has become widespread; mainly these techniques deal with common
      bile duct stones. Fluoroscopy is usually employed, and chronic exposure to X-ray,
      in spite of the relative low dose, can lead to potentially unhealthy conditions
      such as malignancies like bone marrow and other solid cancers. A median of 18
      years of life is lost per fatal cancer, including the time of latency since
      exposure. Nor should one forget benign condition such as cataracts that can lead
      to partial or complete blindness and which surely impair life's quality. METHODS:
      Simulated examinations were carried at the University Hospital (Sao Paulo,
      Brazil) using an anthropomorphic phantom in place of the physician. Four sets of
      dosimeters were placed in the forehead, neck, torso, and lower abdomen (with and
      without a lead apron) and standard ERCP fluoroscopic techniques were employed.
      RESULTS: The dose equivalents were calculated and compared to the recommended
      exposure doses of national and international boards of radiation protection.
      CONCLUSIONS: Based on the results found and compared to standards, working safely
      means: (1) A lead (0.5 mm thickness) apron is fundamental. Without it less than
      one ERCP?month should be performed. (2) With an apron, 23 examinations/month are
      allowed. (3) No thyroid protection grants only 19 exams/month. (4) Performing
      ERCP without lead glasses is hazardous to the eye, allowing only seven ERCPs
      monthly.

PMID- 9171118
TI  - The influence of laparotomy and laparoscopy on tumor growth in a rat model.
AB  - BACKGROUND: The effects of laparotomy and laparoscopy with different gases on
      subcutaneous and intraperitoneal tumor growth have not been evaluated yet.
      METHODS: Tumor growth of colon adenocarcinoma DHD/K12/TRb was measured in rats
      after laparotomy, laparoscopy with CO2 or air, and in control group. Cell
      kinetics were determined after incubation with carbon dioxide or air in vitro and
      tumor growth was measured subcutaneously and intraperitoneally after surgery in
      vivo. RESULTS: In vitro, tumor cell growth increased significantly after
      incubation with air and CO2. In vivo, intraperitoneal tumor weight was increased
      after laparotomy (1,203 +/- 780 mg) and after laparoscopy with air (1,085 +/- 891
      mg) and with CO2 (718 +/- 690 mg) compared to control group (521 +/- 221 mg) (p <
      0.05). Subcutaneous tumor growth was promoted after laparotomy (71 +/- 35 mg) and
      even more after laparoscopy with air (82 +/- 45 mg) and CO2 (99 +/- 55 mg)
      compared to control group (36 +/- 33 mg). CONCLUSIONS: Insufflation of air and
      CO2 promote tumor growth in vitro. In vivo, intraperitoneal tumor growth seems to
      be promoted primarily by intraperitoneal air and subcutaneous tumor growth by
      CO2.

PMID- 9171119
TI  - A murine model of laparoscopic-assisted intervention.
AB  - BACKGROUND: In order to better investigate the effects of laparoscopic surgery,
      it is necessary to establish reliable, reproducible, and economical animal models
      of laparoscopic intervention. Here we describe a mouse model of laparoscopic
      assisted colon resection. METHODS: After successful induction of anesthesia the
      mouse is placed in Trendelenburg position and the peritoneal cavity is
      insufflated with carbon dioxide gas through an angiocatheter placed in the right
      upper quadrant. A 4-mm rigid scope with camera attachment is then inserted
      through a midline port created just caudal to the xiphoid. A second port is then
      created in the right lower quadrant to allow introduction of laparoscopic forceps
      into the peritoneal cavity. The cecum, which extends 1.5 cm beyond the ileocecal
      valve, is grasped with forceps and exteriorized through the operative port.
      Extracorporeally, the cecum is ligated and resected before the cecal stump is
      returned to the peritoneal cavity. The abdominal wall defects are then stapled
      closed. RESULTS: This simple model can be mastered by individuals with very
      limited surgical experience. This laparoscopic model has been used successfully
      in our laboratory in a number of experiments with an intraoperative complication
      rate of 3. 2% (3/94), which was similar to the open surgery group rate of 2.1%
      (2/95, p = 0.99 by chi square). We observed no postoperative leaks in either
      group. The only postoperative death occurred in the open resection group due to
      dehiscence of the laparotomy wound. CONCLUSIONS: We propose that this model may
      be useful for comparing the effects of open to laparoscopic surgery.

PMID- 9171120
TI  - Laparoscopic partial fundoplication vs laparoscopic Nissen-Rosetti
      fundoplication. Short-term results of 231 cases.
AB  - BACKGROUND: Since 1992, all patients at our institution who have met standard
      accepted criteria for surgical intervention for complicated gastroesophageal
      reflux disease have been entered into a prospective sequential clinical study to
      evaluate outcomes of the laparoscopic approach to the Nissen-Rosetti procedure
      and a modified Toupet procedure. METHODS: A standardized workup with upper GI
      series, esophagography, and endoscopy was used in all patients. Manometry, pH
      testing, and other special tests were used selectively. A measuring technique was
      used to determine wrap size without the use of dilators. The short gastric
      vessels were left intact in all patients. A cosurgeon approach was used, with
      technical factors described herein. RESULTS: Some 226 of 231 cases were completed
      laparoscopically (98%)-125 patients in the Nissen-Rosetti group and 101 in the
      partial fundoplication group. There were no clinical failures in either group.
      The partial fundoplication group performed better than the Nissen-Rosetti group
      in all categories of comparison. Return to normal eating habits was much earlier
      in the partial wrap group (p < 0.0001). Postop distal esophageal sphincter
      pressures in the two groups were equal at 15 mmHg. Eight patients suffered
      significant dysphagia requiring endoscopy and dilatation, all in the Nissen
      Rosetti group (p < 0.01). Minor complications occurred in 12% of the total group.
      There was a total surgical revision rate of 3%. There were no gastric or
      esophageal perforations. Average operative time was 30 min. Average hospital stay
      was 1.4 days. Hospital charges for the laparoscopic approach averaged $6,000
      dollars compared to $12,000 for the open approach. CONCLUSION: Laparoscopic
      partial fundoplication is as effective as laparoscopic Nissen-Rosetti
      fundoplication, with a higher satisfaction rate and fewer side effects. Measuring
      for wrap and hiatus size eliminates the need for and risk of using stiff
      dilators. By utilizing cosurgeons and currently available technology, cost,
      operative time, hospital time, and complications can be reduced to a finite
      minimum.

PMID- 9171122
TI  - Laparoscopic cholecystectomy in the elderly.
AB  - BACKGROUND: Advanced age with its concomitant comorbid conditions may be
      associated with increased postoperative laparoscsopic cholecystectomy (LC)
      complications and more frequent conversion to open cholecystectomy (OC). The
      purpose of this study was to evaluate the outcome of LC in patients age 65 and
      older. METHODS: Ninety consecutive patients were studied age 65 and older, of
      whom 39 (43%) were males and 51 (57%) were females, mean age 74 years (range 65
      98), with 20 patients (22%) >/= 80. Indications for surgery included biliary
      colic 55 (61%), acute cholecystitis 22 (24%), pancreatitis 10 (11%), and
      cholangitis 3 (4%). Seventeen patients (19%) had preoperative ERCP, 12 of which
      were normal; five had sphincterotomy with stone extraction. Comorbid conditions
      included hypertension (44%), CAD (17%), cardiac arrhythmias (18), CHF (9%), and
      COPD (7%). RESULTS: Operative time-mean 1 h 51 min +/- SD 43 min. Conversion to
      OC-three patients (3%). Length of stay-mean 5 days (range 1-26). Mortality-two
      patients (2%) >80 years old, one patient with septicemia and multiorgan failure
      whose comorbid diseases included CAD, C.F., COPPED, and elevated BP, one patient
      with MI postsurgery, morbid diseases included DM and CAD. Complications-five
      patients (5%): bile leak from cystic duct stump (one), postsurgery MI (two),
      incarcerated incisional hernia (one), septicemia (one). CONCLUSION: Morbidity
      rates for LC in the elderly population are not different from that reported for
      patients less than 65 years of age. (5% vs 6%, Fried et al., Surg Clin North Am
      1994;74 [2]: 375-387). Our 2% mortality rate is statistically different from
      previously reported in a series of patients of all ages (0.6%, Fried et al.). The
      3% rate of conversion to OC in this older population is not significantly
      different from the patients in Fried et al. series (4%).

PMID- 9171121
TI  - Prospective evaluation of a minimally invasive approach for treatment of bile
      duct calculi in the high-risk patient.
AB  - BACKGROUND: The best approach to bile duct stones in high-risk patients is
      controversial. We showed in a randomized trial that open surgery had a morbi
      mortality similar to that of endoscopic sphincterotomy alone (ES) and less late
      biliary complications. The aim of this study was to evaluate a minimally invasive
      approach to duct stones in high-risk patients compared with open surgery or ES
      alone. METHODS: Sixty high-risk patients (mean age 80 years) suspected of duct
      stones were treated by ES + laparoscopic cholecystectomy (LC). High-risk factors
      were: age > 70 years, Goldman cardiac index > 13, chronic pulmonary disease,
      liver cirrhosis, neurologic deficit, and severe obesity. RESULTS: ERCP success
      was 87%. Duct stones were found in 75%. LC succeeded in 92%. Post-LC stay was 4
      days. Overall morbidity was 19% and mortality was 3%. Recurrent symptoms (mean
      follow-up: 9 months) was 3.6%. When compared with open surgery or ES alone, ES +
      LC had a similar morbi-mortality, but shorter postop stay (p < 0.001). Late
      symptoms appeared in 20% after ES alone vs 4% after open surgery or ES plus LC (p
      < 0.04). CONCLUSIONS: Combined ES + LC is an effective alternative to open
      surgery or ES alone for treatment of duct stones in high-risk patients.

PMID- 9171123
TI  - Laparoscopic douglasectomy in the treatment of painful uterine retroversion.
AB  - BACKGROUND: One of the etiologies of pelvic pain in women, often unrecognized, is
      the Masters-Allen syndrome, which was described in 1955 as the "universal joint
      cervix" syndrome. It has the following three elements: (1) etiology: obstetrics
      related trauma; (2) clinical findings: uterine retroversion with hypermobile
      cervix following elongation or desinsertion of the uterosacral ligaments; (3)
      anatomy: visualization of a tearing of the posterior serosa and subperitoneal
      fascia of the ligamentum latum. METHODS: Forty-one laparoscopic Douglasectomies
      with uterosacral ligamentopexy were performed in the department of Gynecology at
      the University Hospital of Caen during the period between 1990 and 1995 in
      patients with painful retroverted uterus. The patient selection was made thanks
      to the "pessary test." The surgical endoscopic procedure, identical to the
      operation first promoted by Jamain and Letessier in 1976 by laparotomy, is
      described. RESULTS: Total pain relief was experienced by 31 patients (75%) and
      partial relief by five patients (5%). Two main complications occurred, requiring
      one laparotomy (bleeding from a pelvic varicose vein with a concomitantly
      occurring breakdown of the washing-aspiration system) and one second laparoscopy
      at day 15 (one case of hematoma below the peritonization revealed by pain).
      Twenty-three women became pregnant again, and had normal deliveries except for
      two cesareans, with no recurrence of pain. Douglasectomy is compared to
      alternative techniques in the literature. Other indications for Douglasectomy are
      discussed. CONCLUSION: Douglasectomy is the only definitive procedure for
      restoring normal anatomy of the pelvic floor in case of painful uterine
      retroversion occurring in a setting of Masters-Allen syndrome. Additionally, it
      provides for pathological analysis of the excised peritoneum. The results of this
      procedure are excellent when the indication is correctly set, particularly as
      concerns positive pessary testing.

PMID- 9171124
TI  - Laparoscopic bowel mobilization combined with intraoperative colonoscopic
      polypectomy in patients with an inaccessible polyp of the colon.
AB  - BACKGROUND: The purpose of this report was to describe a simple technique
      suitable for polyps where circumstances of the bowel anatomy prevent complete
      access and control of the colonoscopic procedure. METHODS: By combining
      laparoscopic mobilization of the bowel with colonoscopic polypectomy, previously
      inaccessible polyps could be snared in two patients. RESULTS: Both patients had 3
      cm large sessile adenomas in the sigmoid colon safely removed, and they returned
      home within a day. CONCLUSIONS: The described procedure increases the safety of
      the otherwise difficult polypectomy and also avoids laparotomy with enterotomy or
      bowel resection as the alternative.

PMID- 9171125
TI  - Laparoscopic cholecystectomy using abdominal wall retraction. Hemodynamics and
      gas exchange, a comparison with conventional pneumoperitoneum.
AB  - BACKGROUND: Disadvantages related to CO2 pneumoperitoneum have led to development
      of the abdominal wall retractor (AWR), a device designed to facilitate
      laparoscopic surgery without conventional pneumoperitoneum (15 mmHg CO2). We
      investigated the effects of the AWR on hemodynamics and gas exchange in humans.
      We also investigated whether the use of an AWR imposed extra technical
      difficulties for the surgeon. A pilot study revealed that cholecystectomy without
      low-pressure pneumoperitoneum was technically impossible. METHODS: A prospective
      randomized controlled trial: Twenty patients undergoing laparoscopic
      cholecystectomy were randomly allocated into group 1: AWR with low-pressure
      pneumoperitoneum (5 mmHg), or group 2: conventional pneumoperitoneum (15 mmHg).
      RESULTS: Surgery using the AWR lasted longer, 72 +/- 16 min (mean +/- SD) vs 50
      +/- 18 min compared with standard laparoscopic cholecystectomy. There were no
      differences between the groups with respect to hemodynamic parameters, although a
      small reduction of the cardiac output was observed using conventional
      pneumoperitoneum (from 3.9 +/- 0.7 to 3. 2 +/- 1.1 l/min) and an increase during
      AWR (from 4.2 +/- 0.9 to 5.2 +/- 1.5 l/min). Peak inspiratory pressures were
      significantly higher during conventional pneumoperitoneum compared to AWR. A
      slight decrease in pH accompanied by an increase in CO2 developed during
      pneumoperitoneum and during the use of the AWR. In both groups arterial PO2
      decreased. CONCLUSIONS: The results indicate that the view was impaired during
      use of the AWR and therefore its use was difficult and time-consuming. Possible
      advantages of this devices' effects on hemodynamics and ventilatory parameters
      could not be confirmed in this study.

PMID- 9171126
TI  - Early international results of laparoscopic gastrectomies.
AB  - BACKGROUND: The first totally laparoscopic Billroth II gastrectomy was performed
      in 1992. To date, laparoscopic gastrectomy has been performed by a small number
      of surgeons around the world and the laparoscopic approach has been extended to
      Billroth I and total gastrectomy. The aim of this study is to review the state of
      laparoscopically performed gastrectomies in the international scene. METHODS:
      Questionnaires were prepared and sent to every surgeon in the world known by the
      authors or their contacts to have performed a laparoscopic gastrectomy. A
      questionnaire survey was started in July 1994 and completed by November 1994.
      Data collected included age, sex, type of gastric resection, technique of
      reconstruction after resection, average duration of surgery, time to liquid and
      solid intake, postoperative hospital stay, complications, and opinions of the
      surgeons. RESULTS: Sixteen surgeons contributed to this study. A total number of
      118 cases of laparoscopic gastrectomies, comprising Billroth I (11), Billroth II
      (87), vagotomy and antrectomy (10), and total gastrectomy (10) had been
      performed. The indications were gastric and/or duodenal ulcers and benign and
      malignant gastric tumors. CONCLUSIONS: Laparoscopic gastrectomy was found to be
      superior to the open technique by 10 of 16 surgeons because of faster recovery,
      less pain, and better cosmesis. The procedure was an expensive and long operation
      according to four. Two surgeons were uncertain of any benefit because of limited
      experience.

PMID- 9171127
TI  - Port site electrosurgical (diathermy) burns during surgical laparoscopy.
AB  - BACKGROUND: Direct and capacitive coupling of diathermy current have been
      reported as causes of occult injury during surgical laparoscopy. METHODS: In
      order to determine the incidence of electrosurgical injury adjacent to metal and
      plastic cannulas, skin biopsies at 19 port sites used for monopolar
      electrosurgery were analyzed for coagulative necrosis. Prior to surgery the
      cannulas were randomized to either metal or plastic. RESULTS: Coagulative
      necrosis was observed at nine electrosurgery port sites compared to only one
      control (chi2 = 4.872; df = 1; 0.05 > p > 0.02). Plastic cannulas afforded no
      greater protection from skin burns than metal cannulas. CONCLUSIONS: Burns may be
      the result of direct or capacitive coupling to metal cannulas or capacitive
      coupling to the skin edge across plastic cannulas. The potential exists for burns
      to other tissues also in close proximity to a cannula used for electrosurgery.

PMID- 9171128
TI  - Complications of pediatric laparoscopic surgery.
AB  - BACKGROUND: Surgical complications of laparoscopy most often occur during Veress
      needle or primary trocar placement. Veress needle punctures are insignificant and
      require no further treatment, whereas trocar-induced vascular injuries can be
      catastrophic. The frequency of vascular and viscus injuries is difficult to
      calculate because several complications are not reported in the literature.
      METHODS: During a 10-year-period (1984-1995), at the Division of Pediatric
      Surgery at "Federico II" University of Naples, 430 laparoscopic procedures were
      performed in 395 children with a mean age of 5 years. The incidence of
      complications related to laparoscopy was 1.8% with eight complications, one of
      which was rather severe. The complications included one abdominal wall hematoma,
      two perforations of abdominal viscus (stomach, ovary), one umbilical scar
      complication, one postoperative hydrocele, one subcutaneous emphysema, and one
      pneumothorax during a Nissen procedure. The only severe complication occurred in
      a young girl with neurologic problems and a kyphoscoliosis operated on via
      laparoscopy for a gastroesophageal reflux. She suffered injuries of both right
      common iliac vessels and several intestinal perforations due to blind
      introduction of the first umbilical trocar. RESULTS: In this case rapid
      conversion, complex vascular reconstruction, and multiple intestinal sutures were
      performed. The Nissen fundoplication with pyloroplasty was performed
      traditionally and the patient left the hospital free of symptoms after 20 days.
      The other seven complications were resolved without any problem intra- or
      postoperatively. CONCLUSIONS: The authors believe that the open approach with a
      blunt trocar is most important in helping to avoid complications in pediatric
      laparoscopy.

PMID- 9171129
TI  - First results of laparoscopic gastrostomy.
AB  - BACKGROUND: Laparoscopic gastrostomy as an alternative to open gastrostomy was
      introduced with various technical variants 5 years ago. However, long-term
      results of these new methods are still lacking. METHODS: From 4/1993 to 2/1996,
      laparoscopic gastrostomies were performed on 42 patients (50.9 +/- 15.6 [24-71]
      years) with esophageal stenosis in locally advanced hypopharyngeal (17 patients)
      or oropharyngeal (nine patients) carcinoma, incurable esophageal carcinoma (13
      patients) and cerebral dyspagia (three patients). Operating time was 38 +/- 11
      min [15-65 min]. Procedure-related mortality was 0%. Major complications occurred
      in 2/42 (4.7%) patients; minor complications were found in 4/42 (9.4%) patients.
      During a total usage time of 427 months, 14 stoma infections occurred (0.11
      infections/100 days). CONCLUSION: Laparoscopic gastrostomy allows a safe, fast,
      and cheap reestablishment of enteral nutrition. The procedure is minimally
      invasive and can also be performed under local anesthesia. It has become our
      method of choice in patients with malignant, nonresectable subtotal stenosis of
      the hypopharynx or esophagus.

PMID- 9171131
TI  - Laparoscopic repair of a diaphragmatic hernia through the foramen of morgagni.
AB  - A 78-year-old woman is described who presented with a diaphragmatic hernia
      through the foramen of Morgagni. A definitive diagnosis was confirmed by a
      sagittal view on magnetic resonance imaging prior to surgery. The hernia was
      repaired laparoscopically under an abdominal wall lifting technique without
      pneumoperitoneum, and her symptoms completely resolved postoperatively with no
      evidence of recurrence. The laparoscopic repair was considered a suitable and
      safe procedure for the treatment of a Morgagni hernia.

PMID- 9171130
TI  - Long-term effects of repeated injection sclerotherapy on esophageal motility and
      mucosa.
AB  - BACKGROUND: Endoscopic sclerotherapy (ST), widely used as treatment of bleeding
      esophageal varices, might cause motility disturbances of the esophagus as well as
      mucosal damage. We performed this study to evaluate the long-term effects of
      repeated sclerotherapy on esophageal motility and mucosa. METHODS: Ten patients
      with liver cirrhosis and bleeding esophageal varices treated with repeated ST
      were evaluated after the last ST, median 52 months, by esophageal manometry and
      gastroscopy where forceps biopsies were taken. RESULTS: We found a significant
      difference in the distal esophageal sphincter intraabdominal length. The distal
      esophageal sphincter pressure was somewhat lower in the ST group although the
      difference did not reach statistical significance. There was infiltration of
      neutrophil leukocytes in biopsies from four patients and normal findings in the
      rest. CONCLUSIONS: Long-term follow-up evaluation showed statistically longer
      distal esophageal intraabdominal length in the ST group. No mucosal alterations
      were found at the histopathological investigation.

PMID- 9171132
TI  - Long-term results after laparoscopic cholecystotomy in a child with symptomatic
      gallstone disease.
AB  - Cholecystotomy has been suggested for symptomatic gallstone disease in selected
      children. This suggestion is supported by a potential reduction in the frequency
      of the so-called postcholecystotomy syndrome. To our knowledge, laparoscopic
      cholecystotomy has not been reported yet. However, gallstone recurrence has been
      reported up to 4 years after conventional cholecystotomy and therefore we waited
      to publish our results for that period of time. A 12-year-old girl with
      idiopathic symptomatic gallstone disease and a normal kinetic of the gallbladder
      underwent laparoscopic cholecystotomy. The laparoscopic technique was similar to
      laparoscopic cholecystectomy but the gallbladder was left in place and multiple
      gallstones were removed. Intraoperative cholecystoscopy revealed three additional
      small stones. They were removed by subsequent lavage of the gallbladder.
      Choledocholithiasis was excluded by intraoperative cholangiography and the
      gallbladder was closed using an Endo GIA. There were no intraoperative or
      postoperative events. The patient is free of complaints without recurrent
      gallstones on ultrasound examination today, 4 years after the operation.
      Laparoscopic cholecystotomy represents a feasible alternative to laparoscopic
      cholecystectomy.

PMID- 9171133
TI  - Endoscopic hydrostatic balloon dilation of ulcer-induced pyloric stenosis in
      rheumatoid arthritis and secondary amyloidosis.
AB  - We describe a 50-year-old Japanese woman with rheumatoid arthritis who presented
      with near-complete gastric outlet obstruction. The patient also suffered from
      secondary gastrointestinal and cardiac amyloidosis. Gastroscopy revealed multiple
      huge gastric antral ulcers in which amyloid deposits were identified on
      histologic examination. The ulcers became scars after treatment with omeprazole,
      which cause in severe pyloric stenosis. Endoscopic hydrostatic balloon dilation
      under fluoroscopic guidance was performed twice for 10 min. The pyloric outlet
      remained sufficiently patent 22 months later.

PMID- 9171134
TI  - Palliative gastrojejunostomy. A minimally invasive approach.
AB  - Palliative bypass for neoplastic gastric outlet obstruction should be minimally
      invasive. We designed a laparoscopically assisted approach that appears to meet
      the need. The proximal jejunum is exteriorized by laparoscopy via an epigastric
      trocar-site incision. An EEA anvil is installed in the exteriorized jejunum,
      which is returned to the abdomen. Through this mini-incision, the anterior wall
      of the stomach is opened for insertion of the EEA stapler, which penetrates the
      posterior gastric wall. When snapped to the anvil and fired, an antecolic
      gastrojejunostomy is created. No mortality or anastomotic leak occurred in two
      cases. The operation and recovery appeared to be faster than historic controls.
      This operation is minimally invasive and expeditious, ideal for patients
      requiring palliative bypass.

PMID- 9171136
TI  - Laparoscopic-assisted abdominoperineal resection in the prone position. An
      alternative technique.
AB  - With the introduction of laparoscopic-assisted abdominoperineal resection (LAPR),
      the traditional Lloyd-Davies position with the Mayo two-team combined approach is
      being adapted. The Lloyd-Davies position allows two teams of surgeons to work
      simultaneously, minimizing operating time. The conditions required for
      laparoscopy restrict a simultaneous procedure. Since LAPR is typically performed
      as a two-stage procedure, we introduce an alternative position which facilitates
      the perineal dissection. We review the results and technique of LAPR in the prone
      position in three patients who were suitable candidates for this procedure. Three
      patients underwent LAPR. No operative or postoperative complications were
      encountered and the procedures were in keeping with oncologic principles of
      resection. Total anesthesia times were less than 3.5 h for these initial
      patients. No hemodynamic problems were encountered due to the choice of patient
      positioning. The prone jackknife position greatly increases visualization of deep
      structures, reduces blood loss, enhances dissection, and reduces the technical
      demands of the laparoscopic portion of the procedure.

PMID- 9171138
TI  - A three-trocar technique for limited laparoscopic renal surgery.
AB  - Laparoscopic renal surgery usually involves the use of five or six trocars. This
      report concerns the authors' technique for performing such surgery through only
      three trocars. Semilateral patient positioning, along with additional table
      rotation, is utilized to facilitate visceral rotation and optimize exposure of
      the kidney. Four laparoscopic renal procedures were performed: one renal cyst
      decortication and three upper pole partial nephrectomies with ureterectomies for
      duplications of the collecting system. Mean operative time was 148 min with no
      conversions; there were no intra- or postoperative complications. All patients
      tolerated a liquid diet on postoperative day 1, and the median hospital stay was
      2 days. In selected cases laparoscopic renal surgery may be approached safety
      through three trocars.

PMID- 9171137
TI  - Balloon dissection of the space of Bogros via the femoral canal for total
      extraperitoneal laparoscopic herniorrhaphy.
AB  - To obviate the need for general anesthesia or dissection of the rectus sheath, we
      have transferred laparoscopic herniorrhaphy back to the groin by first dissecting
      the suprainguinal parietoperitoneal space of Bogros via the femoral canal.
      Cadaver dissections demonstrated that the preperitoneal plane could be routinely
      fingered and distended with a digitally placed balloon introduced through a 1-cm
      incision immediately below the inguinal ligament. A 10-mm femoral laparoscopic
      port was then inserted and pressurized, allowing two standard 5-mm ports to be
      introduced from above, through the lower quadrant, under vision. The procedure
      was then carried out in the usual way, the mesh being inserted from below. Ten
      patients (two women), 23-73 years old, selected because general anesthesia was
      inadvisable, underwent uncomplicated prosthetic repair of unilateral (eight) or
      bilateral (two) inguinal defects. Half of the peritoneal sacs were pushed up and
      out of the inguinal canal; 18 months later there were no recurrences (inguinal or
      femoral). Preliminary experience with this new technique is promising. It may
      prove applicable to retroperitoneal exposure of the distal aorta and iliac
      vessels, allowing laparoscopic bypass for Leriche syndrome.

PMID- 9171139
TI  - The totally extraperitoneal laparoscopic hernia repair.

PMID- 9171141
TI  - The influence of pneumoperitoneum on the peritoneal implantation of free
      intraperitoneal cancer cells.

PMID- 9171143
TI  - Simplified echocardiography in the diagnosis of heart failure.
AB  - Echocardiography is essential in the diagnosis of heart failure, but insufficient
      resources limit its use. We compared swift (five minutes) simplified
      echocardiography, using elementary equipment, with standard echocardiography (45
      minutes), using advanced equipment. Visual semi-quantification of cardiac
      dimensions, valvular stenosis, and left ventricular ejection fraction (LVEF) was
      performed in 100 consecutive patients with suspected or known heart failure.
      Agreement between simplified and standard echocardiography was 78-89% regarding
      semi-quantification of cardiac dimensions, and 95-98% for valvular stenosis
      (present/not present). Sensitivity and specificity for simplified
      echocardiography to identify patients with LVEF < 0.40 was 86 and 89%,
      respectively. Simplified echocardiography using elementary equipment could be an
      alternative to standard echocardiography in the diagnosis of heart failure. The
      cost and time saved by using simplified echocardiography allows for more patients
      to be examined, which should be weighed against its accuracy.

PMID- 9171144
TI  - M-mode echocardiography in aortic stenosis. Clinical correlates and prognostic
      significance after valve replacement.
AB  - To relate preoperative findings at M-mode echocardiography to preoperative
      clinical and haemodynamic status and to identify possible echocardiographic risk
      factors for mortality after aortic valve replacement (AVR), 250 patients with AVR
      for aortic stenosis (AS) were studied. In follow-up averaging 3.2 years there
      were 22 early (< 30 days) and 23 late deaths. Rising NYHA function class and
      cardiothoracic index, and left ventricular (LV) failure were related to rising LV
      end-diastolic and end-systolic diameter index (EDDI, ESDI), and to increasing LV
      muscle mass index and decreasing fractional shortening (FS). High peak-to-peak
      systolic aortic valve gradient and LV end-systolic pressure were related to small
      dimensions of LV with increased FS and posterior wall thickness (PWTh). EDDI < or
      = 20 mm/m2 and increasing PWTh were independent risk factors for early mortality.
      Patients with EDDI < or = 20 mm/m2 had normal or supranormal FS. PWTh was the
      only independent risk factor in long-term survival: 5-year rates being 81 +/- 6%,
      94 +/- 3% and 85 +/- 7% for PWTh < or = 13, 14-17 and > or = 18 mm, respectively
      (p = 0.03). Prevalence of concomitant coronary artery disease (CAD) rose with
      decreasing PWTh. Angina pectoris in non-CAD patients was related to very high
      PWTh. Subnormal EDDI was associated with poor surgical outcome, and dilated,
      poorly contracting LV with congestive heart failure prior to AVR. The degree of
      LV hypertrophy seemed to be the dominant risk factor, but confounders included
      myocardial ischaemia due to CAD in low-grade hypertrophy or to hypertrophy per
      se. A hypothetically confounding factor is the reversibility potential of
      moderate or severe LV hypertrophy following AVR.

PMID- 9171145
TI  - Acute rejection diagnosed with computed tomography in a porcine experimental lung
      transplantation model.
AB  - The role of computed tomography (CT) in the diagnosis of acute rejection was
      studied in an experimental lung transplantation model, with 15 left lung
      allotransplantations and six autotransplantations performed on piglets weighing
      16-24 kg. There were 31 episodes of acute rejection. In the allotransplantation
      group the development of acute rejection was monitored 115 times with CT,
      transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL). The stages of acute
      rejection were 1) ill-defined centrilobular micronodules or minimal patchy ground
      glass opacities. 2) dense, small-nodular infiltration or extensive ground-glass
      opacities, and bronchial wall thickening. 3) lung volume loss and dense, patchy
      ground-glass opacities and 4) consolidation of the lung. In the
      autotransplantation group monitoring was done 42 times. After
      allotransplantation, TBB and BAL suggested rejection 60 times and infection 23
      times. CT had 86.7% sensitivity and 85.6% specificity. During the first month
      these figures were, respectively, 71.4% and 84.2%. Rising histologic grade was
      associated with increasing stage of acute rejection on CT, which thus proved to
      be a sensitive and specific method for diagnosing acute rejection of lung
      transplant.

PMID- 9171146
TI  - Radical endarterectomy of severely calcified ascending aorta prevents stroke
      during open-heart surgery.
AB  - In ten patients (7 women), mean age 73 years, with severely calcified ascending
      aorta, aortic valve and coronary artery disease were surgically treated after
      radical endarterectomy of the ascending aorta during cardiopulmonary bypass and
      with or without deep hypothermic total circulatory arrest. One patient died 10
      days and one 11 months postoperatively of complications which neither directly
      nor indirectly could be attributed to the aortic endarterectomy. The eight
      surviving patients are doing well after follow-up averaging 16 months. CT scans 1
      year postoperatively showed no aneurysmal dilation of the ascending aorta or
      aortic dissection distal to the endarterectomy site. Radical endarterectomy of
      calcified ascending aorta thus can be performed with relatively low mortality and
      stroke risk and may be considered in patients undergoing valve replacement and/or
      coronary artery bypass grafting.

PMID- 9171147
TI  - Carpentier-Edwards bioprosthesis. Experiences of 17 years with analysis of risk
      factors of early mortality.
AB  - Isolated aortic (AVR, N = 71), mitral (MVR, N = 103), tricuspid (TVR, N = 3),
      pulmonary (PVR, N = 8), combined AVR + MVR (N = 4), or combined MVR + TVR (N = 2)
      valve replacement with a Carpentier-Edwards porcine bioprosthesis was performed
      in 191 patients between 1979 and 1986. Mean age was 56.9 +/- 17 (range 5-80)
      years in the total cohort. The operative mortality rates were 5.6% and 8.7%,
      respectively, for AVR and MVR. Mean observation time was 8 +/- 4.2 (0-16.7) years
      (total = 1.467 patient-years). Follow-up was 100% complete with respect to
      mortality. There were 78 late deaths (44%). Actuarial survival rates at 5 and 10
      years were 73.2 +/- 5.2 and 52.1 +/- 6.6 for AVR and 76.7 +/- 4.2 and 61.6 +/-
      4.8 for MVR. Coronary artery disease, concomitant coronary artery bypass grafting
      and emergency operation were significant risk factors of early mortality (p <
      0.05). Postoperatively, sepsis and multiorgan failure were associated with early
      mortality (p < 0.05). The 10-year actuarial freedom from structural deterioration
      for AVR was 89 +/- 4.6 and 76.4 +/- 4.3 for MVR. It is concluded that structural
      valve failure is the most important factor that adversely affects the performance
      of Carpentier-Edwards bioprosthesis.

PMID- 9171148
TI  - Release of markers of myocardial and endothelial injury following cold
      cardioplegic arrest in pigs.
AB  - Cold cardioplegic arrest causes reperfusion injury to both endothelium and
      myocardium. We investigated release of troponin-T (TnT), tissue plasminogen
      activator activity (t-PA) and histamine (HA) from the heart before and after 2h
      of cold crystalloid cardioplegia in eight Swedish landrace pigs. Coronary sinus
      blood flow was measured in an external shunt between the coronary sinus and the
      right atrium. TnT, t-PA and HA were measured concomitantly in arterial and
      coronary sinus plasma, and the cardiac release was calculated. Cardiac release of
      TnT increased from 18 (15-25) micrograms/min (median (central 90% percentile))
      before cold cardioplegia to maximum 281 (132-510) micrograms/min 30 min after
      aortic declamping (p < 0.02 vs initial value). t-PA rose from -4 (-52-34) to
      maximum 249 (75-691) IU/min 2 min after declamping (p < 0.01) and thereafter
      returned to baseline levels. The net cardiac release of HA was 72 (-80-1321)
      nmol/min before cardioplegia, rising to 234 (-188-524) after 2 min of reperfusion
      (p < 0.02) and returning to baseline after 30 minutes. We conclude that the
      porcine heart releases t-PA, Tn-T and HA during postcardioplegic reperfusion. The
      differing kinetics of their release may indicate different affection of the
      myocardium and the endothelium. Tn-T, t-PA and HA are potential markers of
      myocardial and endothelial injury in the porcine heart.

PMID- 9171149
TI  - Salvage lung resection for massive hemoptysis after resolution of pulmonary
      aspergillosis in a patient with acute leukemia.
AB  - A 58-year-old woman with acute myelogenous leukemia in complete remission
      underwent successful pulmonary resection for massive hemoptysis occurring after
      resolution of pulmonary aspergillosis. Despite the fact that the role of surgery
      in the treatment of pulmonary mycosis in immunocompromised hosts is still to be
      clearly defined, emergency lung resections can be successfully performed in this
      group of patients with almost immediate recovery of stable clinical parameters.
      Brisk recovery can reduce overall morbidity and mortality and allow for early
      resumption of any necessary treatment for underlying disease.

PMID- 9171150
TI  - Myocardial protection with special reference to ischemic preconditioning. An
      experimental study in the pig using a microdialysis technique.

PMID- 9171151
TI  - Results of patch testing with a specialized collection of plastic and glue
      allergens.
AB  - Patch testing was performed on 235 patients with a specialized collection of
      plastic and glue components. Thirteen percent had a positive response to at least
      one of the allergens. Seventy-four percent of the responses were relevant to
      either the present or a past problem, and 64% were occupationally related. The
      substances that yielded the greater percentage of positive responses were
      ethylenediamine, triethylenetetramine, diethylenetriamine,
      diaminodiphenylmethane, melamine formaldehyde resin, phenol formaldehyde resin,
      cresylglycidylether, phenylglycidylether, and N, N-dimethyl-p-toluidine. Of the
      47 agents used, 26 did not elicit any positive responses. There were few
      distinguishing characteristics between those who exhibited a positive response to
      these agents and those who did not. In 12 cases (5% of those tested), the
      diagnosis of allergic contact dermatitis would have been missed if the plastics
      and glues components were not used.

PMID- 9171152
TI  - A special issue based on the third annual conference of the American Society for
      Neural Transplantation, 1996.

PMID- 9171153
TI  - Neuropsychological functioning following fetal striatal transplantation in
      Huntington's chorea: three case presentations.
AB  - Neurotransplantation has been proposed as a potential treatment for the
      neurodegenerative disorder of Huntington's disease (HD), which currently has no
      effective therapy. While patients with Parkinson's disease have received
      neurotransplantation, until recently no HD patients have undergone
      transplantation for HD with standardized evaluations of their progress following
      surgery. The current report presents the cognitive changes in three patients with
      HD who underwent bilateral transplantation of human fetal striatal tissue. As
      part of the pre- and postsurgical evaluation, all three patients were
      administered a neuropsychological battery sensitive to the cognitive effects of
      HD within 2 mo prior to surgery and at 4-6 mo following transplantation. Four to
      6 mo subsequent to surgery, all patients demonstrated increased scores on some
      measures of cognitive functioning. However, the pattern of changes was not
      uniform across subjects. These findings suggest that fetal striatal
      transplantation may improve some of the cognitive symptoms associated with HD in
      the three reported patients.

PMID- 9171155
TI  - Colonization of neural allografts by host microglial cells: relationship to graft
      neovascularization.
AB  - In order to illuminate functional roles of microglial cells within neural
      allografts, we have transplanted both whole and microglial and endothelial cell
      depleted E14 neural cell suspensions into the intact striatum of Sprague-Dawley
      rats. Following posttransplantation times of up to 30 days, the intrastrial
      allografts were analyzed histochemically using the Griffonia simplicifolia B4
      isolectin, a marker for both microglia and blood vessels. Our results indicate
      that both whole and depleted suspension grafts develop identically in terms of
      neovascularization and microglial colonization. In both types of transplants
      microglial cells appeared before any blood vessels were apparent. The main phase
      of graft vascularization occurred between days 7 and 10 posttransplantation and
      neovascularization was complete by day 21, as revealed by quantitative image
      analysis. Microglial cells, which were present as ameboid cells during early
      posttransplantation times, underwent continuing cell differentiation with time
      that paralleled graft vascular development. By 30 days posttransplantation
      microglia within the grafts had assumed the fully ramified phenotype
      characteristic of resting adult microglia. During graft development and
      vascularization, microglia were often seen in close proximity to ingrowing blood
      vessels and vascular sprouts. In conclusion, our study has shown that microglial
      colonization of grafts and graft vascularization occurs independent of donor
      derived microglial and endothelial cells, and suggests that the great majority of
      microglia and vessels within the graft are host derived. We hypothesize that the
      host microglia invading the allografts play an active role in promoting graft
      neovascularization.

PMID- 9171154
TI  - Fetal grafting for Parkinson's disease: expression of immune markers in two
      patients with functional fetal nigral implants.
AB  - In a number of centers throughout the world, fetal nigral transplantation is
      being performed for the treatment of Parkinson's disease (PD). Clinical results
      have been inconsistent. One parameter that differs among transplant studies is
      the degree and manner by which patients are immunosuppressed following
      transplantation. Indeed, the role of the immune system following fetal grafting
      in humans is not well understood. Recently, two patients from our open label
      trial that received fetal nigral implants have come to autopsy. These patients
      were immunosuppressed with cyclosporin for 6 mo posttransplantation and survived
      for a total of 18 mo postgrafting. Robust survival of grafted dopamine-containing
      cells was observed in both cases. Immunostaining for HLA-DR revealed a dense
      collection of cells within grafts from both cases. HLA-DR staining was rarely
      observed within the host including nongrafted regions of the striatum. A more
      detailed analysis of immune markers was performed in Case 2. Numerous pan
      macrophages, T-cells, and B-cells were observed within graft sites located in the
      postcommissural putamen. In contrast, staining for these immune cells was not
      observed within the ungrafted anterior putamen. These findings suggest that even
      in healthy appearing functional nigral implants, grafts are invaded by host
      immune cells that could compromise their long-term viability and function.
      Alternatively, immune cells are known to secrete trophic factors, which may
      ultimately favor graft survival and function. Further work is needed to
      understand the role of the immune system in fetal grafting.

PMID- 9171156
TI  - Growth properties of neural cell lines immortalized with the tsA58 allele of SV40
      large T antigen.
AB  - In vitro growth properties of three CNS-derived cell lines were compared under a
      variety of culture conditions. The M213-20 and J30a cell lines were each derived
      from embryonic CNS culture with the temperature-sensitive (ts) allele of SV40
      large T antigen, tsA58, while the A7 cell line was immortalized using wild-type
      SV40 large T antigen. Cells immortalized with tsA58 SV40 large T proliferate at
      the permissive temperature, 33 degrees C, while growth is expected to be
      suppressed at the nonpermissive temperature, 39.5 degrees C. Both the M213-20 and
      J30a cell lines were capable of proliferating at 39.5 degrees C continuously for
      up to 6 mo. All three cell lines showed no appreciable differences in growth
      rates related to temperature over a 7-day period in either serum-containing or
      defined serum-free media. The percentage of cells in S-phase of the cell cycle
      did not decrease or was elevated at 39.5 degrees C for all three cell lines.
      After 3 wk at 39.5 degrees C, the three cell lines also showed positive
      immunostaining using two monoclonal antibodies reacting with different epitopes
      of SV40 large T antigen. Double strand DNA sequence analyses of a 300 base pair
      (bp) fragment of the large T gene from each cell line, which included the ts
      locus, revealed mutations in both the J30a and M213-20 cell lines. The J30a cell
      line ts mutation had reverted to wild type, and two additional loci with bp
      substitutions with predicted amino acid changes were also found. While the ts
      mutation of the M213-20 cells was retained, an additional bp substitution with a
      predicted amino acid change was found. The A7 cell line sequence was identical to
      the reference wild-type sequence. These findings suggest that (a) nucleic acid
      sequences in the temperature-sensitive region of the tsA58 allele of SV40 large T
      are not necessarily stable, and (b) temperature sensitivity of cell lines
      immortalized with tsA58 is not necessarily retained.

PMID- 9171157
TI  - Differential dissection of the rat E16 ventral mesencephalon and survival and
      reinnervation of the 6-OHDA-lesioned striatum by a subset of aldehyde
      dehydrogenase-positive TH neurons.
AB  - The retinoic acid-generating enzyme, aldehyde dehydrogenase (AHD), is expressed
      in a subpopulation of dopaminergic neurons found in the substantia nigra. Using
      AHD and tyrosine hydroxylase (TH) as immunohistochemical markers, we determined
      whether differential dissection of the embryonic (E16) ventral mesencephalon (VM)
      into its lateral and medial portions contributed equally to the number of TH
      cells surviving transplantation, if grafted AHD/TH neurons reinnervate the host
      striatum according to their normal projection patterns, and examined the
      functional recovery caused by the implanted cells as assessed by amphetamine
      induced rotation in a 6-OHDA-lesioned model of Parkinson's disease. The embryonic
      tissue was transplanted as solid pieces injected via a 20-gauge lumbar puncture
      needle into the center of the deafferented striatum. Groups received either one
      complete ventral mesencephalic piece (VM), two medial pieces of ventral
      mesencephalic tissue (MVM), or two lateral pieces of ventral mesencephalic tissue
      (LVM). Both VM and MVM groups showed a significant decrease in amphetamine
      induced rotation over time and, there was no difference in the degree of
      reduction observed between the two groups. Histological evaluation of the
      transplants revealed a much larger total number of surviving TH cells in grafts
      from the VM and MVM groups compared to the LVM group. Surviving AHD/TH neurons
      were found in all groups. Whereas TH staining of the transplanted striatum
      displayed a halo of graft-derived fibers all around the transplant and
      integration of these fibers into the host neuropil, AHD staining showed a
      preferential reinnervation of the dorsolateral striatum corresponding to the
      normal projection pattern of AHD/TH neurons. In summary, selective dissection of
      the embryonic ventral mesencephalon is possible, functional recovery as assessed
      by amphetamine-induced rotation in animals transplanted with MVM is similar to
      that seen in animals grafted with VM, and AHD/TH neurons have a selective
      reinnervation pattern in the PD transplantation paradigm. These findings may have
      implications for the grafting of fetal mesencephalic tissue in PD patients.

PMID- 9171158
TI  - Cellular delivery of human CNTF prevents motor and cognitive dysfunction in a
      rodent model of Huntington's disease.
AB  - The delivery of ciliary neurotrophic factor (CNTF) to the central nervous system
      has recently been proposed as a potential means of halting or slowing the neural
      degeneration associated with Huntington's disease (HD). The following set of
      experiments examined, in detail, the ability of human CNTF (hCNTF) to prevent the
      onset of behavioral dysfunction in a rodent model of HD. A DHFR-based expression
      vector containing the hCNTF gene was transfected into a baby hamster kidney
      fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control
      cells and those secreting hCNTF were transplanted bilaterally into rat lateral
      ventricles. Eight days later, the same animals received bilateral injections of
      quinolinic acid (QA, 225 nmol) into the previously implanted striata. A third
      group received sham surgery (incision only) and served as a normal control group.
      Bilateral infusions of QA produced a significant loss of body weight and
      mortality that was prevented by prior implantation with hCNTF-secreting cells.
      Moreover, QA produced a marked hyperactivity, an inability to use the forelimbs
      to retrieve food pellets in a staircase test, increased the latency of the rats
      to remove adhesive stimuli from their paws, and decreased the number of steps
      taken in a bracing test that assessed motor rigidity. Finally, the QA-infused
      animals were impaired in tests of cognitive function-the Morris water maze
      spatial learning task, and the delayed nonmatching-to-position operant test of
      working memory. Prior implantation with hCNTF-secreting cells prevented the onset
      of all the above deficits such that implanted animals were nondistinguishable
      from sham-lesioned controls. At the conclusion of behavioral testing, 19 days
      following QA, the animals were sacrificed for neurochemical determination of
      striatal choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD)
      levels. This analysis revealed that QA decreased striatal ChAT levels by 35% and
      striatal GAD levels by 45%. In contrast, hCNTF-treated animals did not exhibit
      any decrease in ChAT levels and only a 10% decrease in GAD levels. These results
      support the concepts that implants of polymer-encapsulated hCNTF-releasing cells
      can be used to protect striatal neurons from excitotoxic damage, produce
      extensive behavioral protection as a result of that neuronal sparing, and that
      this strategy may ultimately prove relevant for the treatment of HD.

PMID- 9171159
TI  - Intranigral grafts of fetal ventral mesencephalic tissue in adult 6
      hydroxydopamine-lesioned rats can induce behavioral recovery.
AB  - Intrastriatal grafts of fetal ventral mesencephalon in rats with unilateral 6
      hydroxydopamine lesions can reduce and even reverse rotational behavior in
      response to direct and indirect dopamine agonists. These grafts can ameliorate
      deficits on simple spontaneous behaviors, but do not improve complex behaviors
      that require the skilled integration of the use of both paws. We report here that
      rats with grafts into the DA-depleted substantia nigra, that receive cyclosporine
      A, can experience recovery on spontaneous behaviors that mimic those observed in
      Parkinson's disease. Specific cyclosporine A treatment conditions can
      differentially affect whether intranigral grafts normalize paw use during
      initiation or termination of a movement sequence. These findings may have
      important implications for the treatment of Parkinson's disease.

PMID- 9171161
TI  - The age of striatum determines the pattern and extent of dopaminergic
      innervation: a nigrostriatal double graft study.
AB  - In animal models of Parkinson's disease, transplanted fetal mesencephalic
      dopaminergic neurons can innervate the dopamine-depleted host brain, but it is
      unclear why large portions of the host striatum are left uninnervated. During
      normal development, the dopaminergic innervation first occurs in the form of a
      dense patchy pattern in the striatum, followed by a widespread nerve fiber
      network. Using intraocular double grafts we have investigated dopaminergic growth
      patterns initiated when ventral mesencephalic grafts innervate striatal targets.
      The fetal lateral ganglionic eminence was implanted into the anterior eye
      chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and
      placed in contact with the first graft. In other animals the two pieces of tissue
      were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry
      revealed a pattern of dense TH-positive patches throughout the total volume of
      the striatal grafts in simultaneously transplanted cografts, while a widespread,
      less dense, pattern was found when mature striatal transplants were innervated by
      fetal dopaminergic grafts. To investigate which type or types of growth patterns
      that developed after grafting to striatum in situ of an adult host, fetal ventral
      mesencephalic tissue was implanted into the lateral ventricle adjacent to the
      dopamine-lesioned striatum. After maturation of the mesencephalic graft, the
      fetal lateral ganglionic eminence was implanted into the reinnervated part of the
      host striatum. TH immunohistochemistry revealed a few nerve fibers within the
      striatal graft and the growth pattern was of the widespread type. In conclusion,
      grafted dopaminergic neurons preferably innervate mature striatum with a
      widespread sparse nerve fiber network, while the innervation of the immature
      striatum occurs in the form of dense patches. Furthermore, when the patchy
      pattern is formed, the total volume of the striatal target is innervated while
      growth of the widespread type terminates prior to reaching distal striatal parts.
      Thus, the growth pattern seems essential to the final volume that is innervated.
      Once the widespread growth pattern is initiated, the presence of immature
      striatum does not change the dopaminergic growth pattern.

PMID- 9171160
TI  - Addition of lateral ganglionic eminence to rat mesencephalic grafts affects fiber
      outgrowth but does not enhance function.
AB  - Addition of embryonic striatal tissue, usually as a combination of the lateral
      and medial ganglionic eminences, to intrastriatal mesencephalic grafts has
      previously been reported to enhance recovery of drug-induced rotational behavior
      in the host and to modify axonal fiber outgrowth from the grafted dopaminergic
      neurons. This study investigated the effects of adding (cografting) either
      lateral or medial ganglionic eminence tissue to embryonic mesencephalic grafts
      implanted intrastriatally, in rats with unilateral 6-hydroxydopamine lesions. The
      cografts did not exhibit increased survival or cell size of dopaminergic neurons
      when compared to transplants of mesencephalic tissue alone. Neither did
      recipients of cografts exhibit any enhancement of graft-induced recovery of
      function, when tested for drug-induced rotational behavior or forelimb function
      in the staircase test. However, cografts containing lateral ganglionic eminence
      displayed patches of dense tyrosine hydroxylase-immunoreactive fibers within the
      graft tissue. These patches largely coincided with patches in adjacent stained
      sections, which were rich in immunostaining for the striatal-specific marker
      dopamine- and cyclic AMP-regulated phosphoprotein-32 (DARPP-32). Such patches
      were not present in rats receiving cografts containing medial ganglionic eminence
      or mesencephalic tissue alone. Thus, it seems that the grafted dopaminergic
      neurons preferentially grow into the areas of the transplants containing lateral
      ganglionic eminence tissue. In summary, the results suggest that embryonic
      lateral ganglionic eminence exerts trophic effects on the outgrowth of
      dopaminergic axons, but does not enhance the behavioral effects of grafted
      dopaminergic neurons.

PMID- 9171162
TI  - The effects of storage conditions and trophic supplementation on the survival of
      fetal mesencephalic cells.
AB  - It is estimated that only 5-10% of dopamine (DA) neurons implanted into the
      striatum of patients undergoing fetal-nigral transplantation as a treatment for
      Parkinson's Disease survive. Because it is often necessary to store fetal tissue
      prior to transplantation, we evaluated various storage parameters that could
      influence DA neuron viability in rostral mesencephalic tegmentum (RMT) cultures
      using tyrosine hydroxylase immunoreactive (THir) cell counts as an index of DA
      neuron survival. A high K+ hibernation media (HM) was used in all studies. We
      found that RMT cell viability and THir cell counts decreased as storage duration
      increased (up to 120 h). Storage at 37 degrees C in HM killed all cells, while
      storage at 10 degrees C yielded higher survival rates than 4 degrees C. In
      comparison to trypsinization, mechanical dissociation of tissue increased cell
      viability. Neutral pH and a storage density of at least 1 x 10(6) cells/mL were
      found to be optimal, while striatal coculture of RMT cells with striatal feeder
      layers increased THir viability up to 16-fold in comparison to monocultures. The
      nurturing effect of striatal coculture may be explained by the release of
      autotrophic factors, and we tested this hypothesis by supplementing the HM with
      human placental cord serum (HPCS, 8%), glial-derived neurotrophic factor (GDNF;
      10 microg/mL), and brain-derived neurotrophic factor (BDNF; 10 microg/mL). GDNF
      and HPCS supplements increased RMT cell viability by 10-15%, while GDNF, BDNF,
      and HPCS increased viability of THir cells by approximately 40% at all time
      points studied. As Klenow enzyme labeling technique indicated that 33% of stored
      RMT cells were undergoing apoptosis, we found that GDNF, BDNF, and HPCS reduced
      apoptosis by 50%. DNA laddering and DAPI nuclear stain confirmed the presence of
      apoptosis in hibernated RMT cells, leading us to postulate that the high
      viability counts seen with trypan blue exclusion are misleading.

PMID- 9171163
TI  - Comparison of neurotoxicity following repeated administration of l-dopa, d-dopa
      and dopamine to embryonic mesencephalic dopamine neurons in cultures derived from
      Fisher 344 and Sprague-Dawley donors.
AB  - Levodopa is the most efficacious and widely used symptomatic drug for Parkinson's
      disease (PD). There is currently, however, a great deal of interest focused on
      the possibility that levodopa-induced increases in dopamine (DA) turnover may
      increase oxidative damage derived from the breakdown of DA. Increased oxidative
      damage following levodopa may contribute to the progressive degeneration of
      remaining host nigral neurons as well as interfere with development and function
      of embryonic nigral neurons in neural grafting trials. There is abundant evidence
      that levodopa is toxic to embryonic nigral DA neurons in both cell culture and
      neural grafting models. These findings have prompted a number of studies on
      mechanisms of levodopa toxicity to identify effective means of ameliorating
      potential oxidative stress related to levodopa in PD. In the current study we
      have utilized cultures of embryonic nigral DA neurons to address the fundamental
      question of whether levodopa-induced toxicity is related to DA production or
      whether dopa itself contributes to cell death. We compared the degree of nigral
      DA cell death following chronic administration of: 1) levodopa (e.g.: l-dopa); 2)
      its less active stereoisomer d-dopa; and 3) DA. We examined the rank order of
      toxicity of these compounds in two species of rats, Fisher 344 (F344) and Sprague
      Dawley (SD). Results indicate a toxicity profile of: DA > l-dopa >> d-dopa. In
      addition, although there was no difference in response of F344 and SD cultures to
      l-dopa, the SD cultures were significantly more susceptible to the neurotoxic
      effects of DA. Taken collectively, these results suggest that levodopa-induced
      toxicity is related primarily to DA production rather than oxidation of dopa to
      toxic metabolites, and that some strain related differences do exist.

PMID- 9171164
TI  - Engraftment of C6-2B cells into the striatum of ACI nude rats as a tool for
      comparison of the in vitro and in vivo phenotype of a glioma cell line.
AB  - The C6-2B is a well-characterized glioma cell line used extensively in the study
      of malignant glial biology. While the C6-2B cell line has traditionally been
      thought of as a homogenous cell line, the in vitro phenotype of the C6-2B cell
      line can vary considerably depending on the culture technique used and the
      stratum on which the cells are grown. Thus, we asked whether the in vitro
      phenotype of the C6-2B cell line was significantly different than the in vivo
      phenotype of the cell line once it was engrafted into the striatum of nude rats.
      Under culture conditions used in our laboratory, 100% of the C6 cells were found
      to express p75, the low-affinity nerve growth factor (NGF) receptor, and Major
      Histocompatability Class I (MHC Class I), while only 10-15% demonstrated vimentin
      reactivity. Immunohistochemistry was consistently negative for GFAP, trkA (the
      high-affinity receptor for NGF), CD4, CD8, and a macrophage specific marker (Ox
      41). Once engrafted into the striatum of nude rats, the cells remained 100% p75
      and MHC Class I positive, and again, only 15% of the cells demonstrated vimentin
      reactivity. The grafted cells retained this characteristic for 28 days in vivo.
      Although an immunoincompetent host was selected to minimize the effects an
      inflammatory response would have on the graft, a transient inflammatory response
      was detected. During the first week of engraftment, numerous MHC class II cells,
      some of which were macrophages, were seen infiltrating the graft. However, by 4
      weeks postengraftment, no inflammatory cells were appreciated in the graft and
      surprisingly little reactive gliosis was seen in the penumbra of the tumor mass.
      Thus, the limited number of in vitro phenotypic characteristics we examined in
      the C6-2B cell line remained constant once the cells were engrafted into the
      striatum of athymic nude rats.

PMID- 9171165
TI  - Altered differentiation of CNS neural progenitor cells after transplantation into
      the injured adult rat spinal cord.
AB  - Denervation of CNS neurons and peripheral organs is a consequence of traumatic
      SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy
      for reinnervating these targets. Neural progenitor cell lines are being
      investigated as alternates to embryonic CNS neurons. RN33B is an immortalized
      neural progenitor cell line derived from embryonic rat raphe nuclei following
      infection with a retrovirus encoding the temperature-sensitive mutant of SV40
      large T-antigen. Transplantation studies have shown that local epigenetic signals
      in intact or partially neuron-depleted adult rat hippocampal formation or
      striatum direct RN33B cell differentiation to complex multipolar morphologies
      resembling endogenous neurons. After transplantation into neuron-depleted regions
      of the hippocampal formation or striatum, RN33B cells were relatively
      undifferentiated or differentiated with bipolar morphologies. The present study
      examines RN33B cell differentiation after transplantation into normal spinal cord
      and under different lesion conditions. Adult rats underwent either unilateral
      lesion of lumbar spinal neurons by intraspinal injection of kainic acid or
      complete transection at the T10 spinal segment. Neonatal rats underwent either
      unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete
      transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B
      cells were transplanted into the lumbar enlargement of injured and age-matched
      normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells
      were found throughout normal rat gray matter. In contrast, only bipolar RN33B
      cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or
      transection rats. These observations suggest that RN33B cell multipolar
      morphological differentiation in normal adult spinal cord is mediated by direct
      cell-cell interaction through surface molecules on endogenous neurons and may be
      suppressed by molecules released after SCI. They also indicate that the fate of
      immortalized neural progenitor cell lines in injured CNS must be stringently
      characterized.

PMID- 9171166
TI  - MAP2 expression in the developing human fetal spinal cord and following
      xenotransplantation.
AB  - Human fetal spinal cord (FSC) tissue was obtained from elective abortions at 6-14
      wk gestational age (GA). The specimens were then either immediately processed for
      immunohistochemical analysis or xenotransplantation. In the latter case, donor
      tissue was prepared as a dissociated cell suspension and then introduced either
      subpially or intraspinally into contusion lesions of the adult rat midthoracic
      spinal cord. The xenografts were subsequently examined by conventional
      histological and immunohistochemical methods at 2-3 mo postgrafting.
      Immunostaining showed that MAP2 was expressed heavily in cells residing in the
      mantle layer of the human fetal spinal cord in situ as early as 6 wk GA. Subpial
      and intraparenchymal xenografts also were intensely immunoreactive for MAP2, but
      no staining of surrounding host neural tissue was detected. We conclude that the
      differential expression of MAP2 can be used to distinguish human graft tissue
      from the surrounding rat spinal cord in this xenograft paradigm. Under
      appropriate staining conditions, MAP2 can thus serve to facilitate analyses of
      host-graft integration, donor cell migration, and neuritic outgrowth.

PMID- 9171167
TI  - Cerebellar grafts partially reverse amino acid receptor changes observed in the
      cerebellum of mice with hereditary ataxia: quantitative autoradiographic studies.
AB  - We used quantitative autoradiography of [3H]CNQX (200 nM), [3H]muscimol (13 nM),
      and [3H]flunitrazepam (10 nM) binding to study the distribution of non-NMDA and
      GABA(A) receptors in the cerebellum of pcd mutant mice with unilateral cerebellar
      grafts. Nonspecific binding was determined by incubation with 1 mM Glu, 200
      microM GABA, or 1 microM clonazepam, respectively. Saturation parameters were
      defined in wild-type and mutant cerebella. In mutants, non-NMDA receptors were
      reduced by 38% in the molecular layer and by 47% in the granule cell layer. The
      reduction of non-NMDA receptors in the pcd cerebellar cortex supports their
      localization on Purkinje cells. [3H]CNQX binding sites were visualized at higher
      density in grafts that had migrated to the cerebellar cortex of the hosts (4.1
      and 11.0 pmol/mg protein, respectively, at 23 and 37 days after grafting) than in
      grafts arrested intraparenchymally (2.6 and 6.2 pmol/mg protein, respectively, at
      23 and 37 days after grafting). The pattern of expression of non-NMDA receptors
      in cortical vs. parenchymal grafts suggests a possible regulation of their levels
      by transacting elements from host parallel fibers. GABA(A) binding levels in the
      grafts for both ligands used were similar to normal molecular layer. Binding was
      increased in the deep cerebellar nuclei of pcd mutants: the increase in
      [3H]muscimol binding over normal was 215% and the increase in [3H]flunitrazepam
      binding was 89%. Such increases in the pcd deep cerebellar nuclei may reflect a
      denervation-induced supersensitivity subsequent to the loss of Purkinje axon
      terminal innervation. In the deep nuclei of pcd mutants with unilateral
      cerebellar grafts, [3H]muscimol binding was 31% lower in the grafted side than in
      the contralateral nongrafted side at 37 days after transplantation;
      [3H]flunitrazepam binding was also lower in the grafted side by 15% compared to
      the nongrafted side. Such changes in GABA(A) receptors suggest a significant,
      albeit partial, normalizing trend of cerebellar grafts on the state of
      postsynaptic supersensitive receptors in the host cerebellar nuclei.

PMID- 9171168
TI  - Functional characterization of NGF-secreting cell grafts to the acutely injured
      spinal cord.
AB  - Previously we reported that grafts of cells genetically modified to produce human
      nerve growth factor (hNGF) promoted specific and robust sprouting of spinal
      sensory, motor, and noradrenergic axons. In the present study we extend these
      investigations to assess NGF effects on corticospinal motor axons and on
      functional outcomes after spinal cord injury. Fibroblasts from adult rats were
      transduced to express human NGF; control cells were not genetically modified.
      Fibroblasts were then grafted to sites of midthoracic spinal cord dorsal
      hemisection lesions. Three months later, recipients of NGF-secreting grafts
      showed deficits on conditioned locomotion over a wire mesh that did not differ in
      extent from control-lesioned animals. On histological examination, NGF-secreting
      grafts elicited specific sprouting from spinal primary sensory afferent axons,
      local motor axons, and putative cerulospinal axons as previously reported, but no
      specific responses from corticospinal axons. Axons responding to NGF robustly
      penetrated the grafts but did not exit the grafts to extend to normal innervation
      territories distal to grafts. Grafted cells continued to express NGF protein
      through the experimental period of the study. These findings indicate that 1)
      spinal cord axons show directionally sensitive growth responses to neurotrophic
      factors, 2) growth of axons responding to a neurotrophic factor beyond an injury
      site and back to their natural target regions will likely require delivery of
      concentration gradients of neurotrophic factors toward the target, 3)
      corticospinal axons do not grow toward a cellular source of NGF, and 4)
      functional impairments are not improved by strictly local sprouting response of
      nonmotor systems.

PMID- 9171169
TI  - Stereotactic biopsy of nonpolar tumors in the dominant hemisphere: a prospective
      study of effects on language functions.
AB  - A prospective study of patients undergoing computerized tomography (CT)-guided
      stereotactic biopsy of nonpolar tumors in the dominant hemisphere was undertaken
      to determine if stereotactic biopsy caused a deterioration of language functions.
      Language was assessed using the Western Aphasia Battery (WAB) and the Boston
      Naming Test (BNT) before and after a biopsy sample was obtained. Of 16 patients
      studied, five (31%) were dysphasic preoperatively. After the biopsy the Aphasia
      Quotient (AQ), derived from the WAB, had significantly deteriorated in four (80%)
      of these patients, whereas in the fifth it remained relatively unchanged. One of
      these patients with an extensive infiltrating hemispheric oligoastrocytoma
      subsequently recovered normal language function after radiotherapy. In 10 of the
      11 patients who had normal language function preoperatively there were no
      deleterious changes after biopsy in either the WAB subtest or BNT scores. In the
      other patient whose WAB score was normal preoperatively, there was a significant
      deterioration in postoperative AQ. This patient, who declined steroid therapy
      before and after biopsy, had a glioblastoma multiforme in Wernicke's area. A
      postoperative CT scan revealed no changes from what was shown on preoperative
      scan. This clinical study shows that CT-guided stereotactic biopsy of nonpolar
      tumors in the dominant hemisphere using the Brown-Roberts-Wells system and the
      Sedan-Nashold biopsy cannula carries a 9% risk (95% confidence intervals 0-26%)
      of impairing language functions if the patient is not dysphasic preoperatively.
      If the patient is dysphasic preoperatively, there is a very high risk of
      aggravating the dysphasia with stereotactic biopsy.

PMID- 9171170
TI  - Prospective study of zero drift in fiberoptic pressure monitors used in clinical
      practice.
AB  - One hundred and one fiberoptic pressure transducers (59 subdural and 42
      ventricular) were studied in 86 patients (some in whom more than one device had
      been inserted). Only four complications occurred: two transient cerebrospinal
      fluid leaks after removal and two clinically insignificant intracerebral
      hematomas. No intracranial infections could be attributed to the devices.
      Technical problems occurred 23 times, with 11 devices ceasing to function before
      removal, seven becoming displaced, and five microventricular catheters failing to
      enter the ventricles. Zero-drift readings were obtained for 83 devices at the
      time of removal (median 66 hours after insertion, range 2 hours-13 days). There
      was a clear negative bias in the readings (median -3), with a wide range of
      values (-12 to +14 mm Hg; interquartile range -6 to -1) that was apparent even in
      the first 3 days of use. There was no important relationship between zero drift
      and any recorded variable. It is concluded that zero drift of fiberoptic pressure
      transducers is a significant problem and that undue reliance should not be placed
      on intracranial pressure readings from these devices in isolation from other
      clinical and radiological information.

PMID- 9171171
TI  - Long-term improvement in patients with severe Parkinson's disease after
      implantation of fetal ventral mesencephalic tissue in a cavity of the caudate
      nucleus: 5-year follow up in 10 patients. Clinica Puerta de Hierro Neural
      Transplantation Group.
AB  - Different groups worldwide have observed in recent years that stereotactic
      implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's
      disease. The authors therefore investigated whether implantation of fetal ventral
      mesencephalic (FVM) tissue via open surgery is also capable of producing an
      improvement and whether this improvement is transient or long lasting. The
      authors report their findings in a 5-year follow-up study in 10 patients with
      Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was
      implanted in a cavity created in the right caudate nucleus. The results indicate
      that the implants improved motor function and that clinical recovery persisted in
      seven of the 10 patients 5 years after implantation. Amelioration was observed in
      both the on and off phases and was accompanied by a 64% reduction in the levodopa
      dose and withdrawal of the dopamine agonist. The on phase was prolonged from 39%
      of the waking day to 72%, with reduced intensity and duration of dyskinesias. All
      symptoms that were analyzed showed improvement, although they differed in
      intensity and time of onset. The course of improvement seemed to be stepwise,
      with significant improvement between 5 and 7 months postimplantation followed by
      two waves of progress peaking in Months 15 and 36. Withdrawal of cyclosporine in
      three patients after more than 2 years of administration produced a decline in
      the patients' clinical conditions. In conclusion, the results indicate that open
      surgery implantation of FVM tissue in the caudate nucleus improves the clinical
      condition of parkinsonian patients and that this improvement can persist for at
      least 5 years. In comparison with two earlier series reported by the authors,
      which involved implants of perfused adrenal medulla and coimplantation of adrenal
      medulla and peripheral nerve, the course and pattern of improvement in these
      implant recipients suggests that their recovery can be attributed to more than
      one factor.

PMID- 9171172
TI  - Anaplastic ependymoma: treatment of pediatric patients with or without
      craniospinal radiation therapy.
AB  - The authors conducted a retrospective review of the clinical and treatment
      characteristics and outcomes in 28 pediatric patients with anaplastic ependymoma
      treated with radiation therapy since the advent of computerized tomography (CT)
      (1978-1994). Twelve patients received craniospinal irradiation followed by a
      boost to the primary site, two received whole-brain radiation therapy followed by
      a boost to the primary site, and the remaining 14 were treated with focal
      radiation therapy. The mean dose to the primary site was 5486 cGy. With a median
      follow-up period of 86 months for the 14 surviving patients (range 31-201
      months), the median disease-free survival, measured from the date of diagnosis to
      the time of recurrence after radiation therapy, was 40 months. The median disease
      free survival measured from the start of radiation therapy was 32 months. The
      median overall survival rate has not been reached and the actuarial estimates of
      overall survival rates at 5 and 10 years were 56% and 38%, respectively.
      According to univariate analysis, the disease-free survival rate was
      significantly improved (p < 0.01) in patients who underwent a gross-total
      resection at diagnosis. Overall survival rates were negatively influenced by
      treatment with craniospinal and whole-brain irradiation. As calculated by
      multivariate analysis, increasing dosage to the primary site (p < 0.05),
      infratentorial location (p < 0.01), and gross-total resections (p < 0.02)
      resulted in the longest disease-free survival times. All 19 patients in whom
      treatment failed after radiation therapy suffered a recurrence at the primary
      site. In addition, one of these patients experienced subarachnoid dissemination.
      Radiation treatment recommendations for patients with ependymoma have been based
      on the tumor's location, perceived risk for dissemination, and malignant
      propensity. The significance of anaplastic histological classification is
      controversial. Differences in the disease-free and overall survival rates have
      been demonstrated between ependymomas and anaplastic ependymomas treated in the
      pre-CT era. The results of this study show that there is no benefit from
      craniospinal irradiation in this group of patients.

PMID- 9171173
TI  - Basilar invagination in osteogenesis imperfecta and related
      osteochondrodysplasias: medical and surgical management.
AB  - Osteogenesis imperfecta (OI) is a heritable disorder of bone development caused
      by defective collagen synthesis. Basilar invagination is an uncommon but
      devastating complication of this disease. The authors present a comprehensive
      strategy for management of craniovertebral anomalies associated with OI and
      related osteochondrodysplasias. Twenty-five patients with congenital
      osteochondrodysplasias (18 OI, four Hajdu-Cheney syndrome, and three
      spondyloepiphyseal dysplasia) and basilar invagination were evaluated between
      1985 and 1995. The male/female ratio in this cohort was 1:1. The mean age at
      presentation was 11.9 years (range 13 months-20 years). Fourteen patients (56%)
      presented during adolescence (11-15 years of age). Symptoms and signs included
      headache (76%), lower cranial nerve dysfunction (68%), hyperreflexia (56%),
      quadriparesis (48%), ataxia (32%), nystagmus (28%), and scoliosis (20%). Four
      patients (16%) were asymptomatic. Seven (28%) had undergone previous posterior
      fossa decompression; one had also undergone ventral decompression. Imaging
      findings included basilar invagination (100%), ventral brainstem compression
      (84%), hydrocephalus (32%), hindbrain herniation (28%), and
      syringomyelia/syringobulbia (16%). Patients with hydrocephalus underwent
      ventricular shunt placement. Reducible basilar invagination (40%) was treated
      with posterior fossa decompression and occipitocervical fusion. Those with
      irreducible ventral compression (60%) underwent transoral-transpalatopharyngeal
      decompression followed by occipitocervical fusion. All patients improved
      initially. However, basilar invagination progressed radiographically in 80%
      (symptomatic in 24%) despite successful fusion. Prolonged external orthotic
      immobilization with the modified Minerva brace afforded symptomatic improvement
      and arrested progression of the deformity. The mean follow-up period was 5.9
      years (range 1.1-10.5 years). Ventral brainstem compression in OI should be
      treated with ventral decompression, followed by occipitocervical fusion with
      contoured loop instrumentation to prevent further squamooccipital infolding.
      Despite fusion, however, basilar invagination tends to progress. Prolonged
      immobilization (particularly during adolescence) may stabilize symptoms and halt
      further invagination. This study represents the largest series to date addressing
      craniovertebral anomalies in OI and related congenital bone softening disorders.

PMID- 9171174
TI  - Radiological and anatomical evaluation of the atlantoaxial transarticular screw
      fixation technique.
AB  - Sixty-one patients treated with C1-2 transarticular screw fixation for spinal
      instability participated in a detailed clinical and radiological study to
      determine outcome and clarify potential hazards. The most common condition was
      rheumatoid arthritis (37 patients) followed by traumatic instability (15
      patients). Twenty-one of these patients (one-third) underwent either surgical
      revision for a previously failed posterior fusion technique or a combined
      anteroposterior procedure. Eleven patients underwent transoral odontoidectomy and
      excision of the arch of C-1 prior to posterior surgery. No patient died, but
      there were five vertebral artery (VA) injuries and one temporary cranial nerve
      palsy. Screw malposition (14% of placements) was comparable to another large
      series reported by Grob, et al. There were five broken screws, and all were
      associated with incorrect placement. Anatomical measurements were made on 25 axis
      bones. In 20% the VA groove on one side was large enough to reduce the width of
      the C-2 pedicle, thus preventing the safe passage of a 3.5-mm diameter screw. In
      addition to the obvious dangers in patients with damaged or deficient
      atlantoaxial lateral mass, the following risk factors were identified in this
      series: 1) incomplete reduction prior to screw placement, accounting for two
      thirds of screw complications and all five VA injuries; 2) previous transoral
      surgery with removal of the anterior tubercle or the arch of the atlas, thus
      obliterating an important fluoroscopic landmark; and 3) failure to appreciate the
      size of the VA in the axis pedicle and lateral mass. A low trajectory with screw
      placement below the atlas tubercle was found in patients with VA laceration. The
      technique that was associated with an 87% fusion rate requires detailed
      computerized tomography scanning prior to surgery, very careful attention to
      local anatomy, and nearly complete atlantoaxial reduction during surgery.

PMID- 9171175
TI  - Revision of anterior cervical pseudoarthrosis with anterior allograft fusion and
      plating.
AB  - Anterior cervical discectomy and fusion is an efficacious procedure used to treat
      a variety of cervical spinal disorders, including spondylosis, myelopathy,
      herniated discs, trauma, and degenerative disc disease. Pseudarthrosis, or
      failure of fusion, may be the most common complication of spinal fusion
      procedures. Nineteen consecutive patients with symptomatic pseudarthrosis
      following failed anterior cervical fusions were treated with anterior cervical
      revision using iliac crest allografts and either the Cervical Spine Locking Plate
      system (10 patients) or the Trapezial Osteosynthetic Plate system (nine
      patients). The mean age of the nine men and 10 women undergoing treatment was
      49.1 years (range 25-72 years). Eleven patients (57.9%) exhibited pseudarthrosis
      at one level, six (31.5%) at two levels, and two (10.5%) at three levels. The
      indications for revision were intractable neck pain with radiculopathy (17
      patients) or myelopathy (two patients), with evidence of pseudarthrosis on plain
      cervical radiography as well as computerized tomography (CT) or single-photon
      emission computerized tomography (SPECT) scanning, or both. All eight patients
      evaluated with SPECT showed increased focal uptake consistent with
      pseudarthrosis, which was subsequently confirmed intraoperatively in all eight.
      The average follow-up period was 22.4 months (range 12-42 months). Solid osseous
      fusion was achieved over all 28 levels in all 18 patients available for follow-up
      review (100%). One patient died 4 months postoperatively from myocardial
      infarction related to preexisting coronary artery disease. There were no
      intraoperative complications; postoperatively, two patients (10.5%) experienced
      transient hoarseness. Anterior revision of failed cervical fusions using
      allograft interbody fusion material and anterior plating is a safe and
      efficacious procedure. In this series, the use of allografts avoided donor site
      morbidity without adversely affecting fusion rates. Rigid internal fixation was
      achieved by means of anterior plating without increasing surgical morbidity
      rates. The SPECT imaging technique has the potential to reliably confirm the
      diagnosis of pseudarthrosis.

PMID- 9171176
TI  - Management of postoperative infections after spinal instrumentation.
AB  - The authors retrospectively reviewed 452 consecutively treated patients who
      underwent a spinal instrumentation procedure at a single institution to establish
      which patients and which surgical approaches might be associated with an
      increased risk of developing deep wound infections and to determine the efficacy
      with which the institution's current treatment strategy eradicates these
      infections. Wound infections occurred in 17 patients (10 men and seven women)
      with spinal instrumentation (incidence 3.8%). All infections occurred after
      posterior spinal instrumentation procedures (7.2%); there were no infections
      after anterior instrumentation procedures regardless of the level. Each patient
      was assigned an infection risk factor (RF) score depending on the number of RFs
      identified in an individual patient preoperatively. The mean RF score of patients
      who developed infections was 2.18, whereas the mean RF score for a procedure
      matched, infection-free control group was 0.71. The mean number of days from
      surgery to clinical presentation was 27.6 days (range 4-120 days), and the mean
      increase in hospitalization time for the subset of patients who developed
      infections was 16.6 days. The most common organism isolated from wound cultures
      was Staphylococcus aureus (nine of 17 cases). Of the 17 patients, five had
      infections involving multiple organisms. All patients were infection free at a
      minimum of 8 months follow-up review. The current treatment regimen advocated at
      this institution consists of operative debridement of the infected wound, a
      course of intravenous followed by oral antibiotic medications, insertion of an
      antibiotic-containing irrigation-suction system for a mean of 5 days, and
      maintenance of the instrumentation system within the infected wound.

PMID- 9171177
TI  - Primary reconstruction for spinal infections.
AB  - Primary reconstruction using bone grafts and instrumentation for spinal
      infections remains controversial. Between 1991 and 1993, 27 infections of the
      spinal column were treated at the Department of Neurosurgery of the University of
      Florida. Of the 27 cases 20 (six cervical, eight thoracic, and six lumbar spine)
      required surgical debridement and spinal reconstruction to maximize eradication
      of the infection and maintenance of spinal alignment. All of the cervical and
      lumbar cases were caused by bacterial infections, and two of eight thoracic cases
      were caused by tuberculous infections. Spinal arthrodesis was performed in all
      cases: interbody grafts were used in 18 procedures and posterolateral onlay
      grafts in 14. Interbody grafts were autologous in 10 cases (six rib and four
      iliac crest) and allograft in eight (six fibular and two humerus). All of the
      posterolateral onlay grafts were autologous (three rib and 11 iliac crest).
      Spinal instrumentation was used in 15 cases: four with Caspar plates and 11 with
      posterior segmental fixation (five hook/rod constructs and six screw/rod
      constructs). Seventeen of 20 patients achieved improved clinical status
      postoperatively and 18 of 20 showed radiographic evidence of bone fusion.
      Antibiotic drugs were administered parenterally for an average of 6 weeks
      followed by a 3-month course of oral antibiotic medications. Tuberculous
      infections were treated for 1 year with antibiotic therapy. The average follow-up
      period was 37 months from surgery and 31 months after completion of treatment
      with antibiotic drugs. The authors conclude that primary arthrodesis and
      instrumentation can be performed in acute spinal infections; however, successful
      management depends on aggressive debridement of infectious foci and prolonged
      treatment with parenteral antibiotic drugs.

PMID- 9171178
TI  - Multilevel anterior cervical corpectomy and fibular allograft fusion for cervical
      myelopathy.
AB  - This study was conducted to determine the safety and efficacy of multilevel
      anterior cervical corpectomy and stabilization using fibular allograft in
      patients with cervical myelopathy. Thirty-six patients underwent this procedure
      for cervical myelopathy caused by spondylosis (20 patients), ossified posterior
      longitudinal ligament (four patients), trauma (one patient), or a combination of
      lesions (11 patients). The mean age (+/- standard deviation) of the patients was
      58 +/- 10 years and 30 of the patients were men. The mean duration of symptoms
      before surgery was 30 +/- 6 months and 11 patients had undergone previous
      surgery. Prior to surgery, the mean Nurick grade of the myelopathy was 3.1 +/-
      1.4. Seventeen patients also had cervicobrachial pain. Four vertebrae were
      removed in six patients, three in 19, and two in 11 patients. Instrumentation was
      used in 15 cases. The operative mortality rate was 3% (one patient) and two
      patients died 2 months postoperatively. Postoperative complications included
      early graft displacement requiring reoperation (three patients), transient
      dysphagia (two patients), cerebrospinal fluid leak treated by lumbar drainage
      (three patients), myocardial infarction (two patients), and late graft fracture
      (one patient). One patient developed transient worsening of myelopathy and three
      developed new, temporary radiculopathies. All patients achieved stable bone union
      and the mean Nurick grade at an average of 31 +/- 20 months (range 0-79 months)
      postoperatively was 2.4 +/- 1.6 (p < 0.05, t-test). Cervicobrachial pain improved
      in 10 (59%) of the 17 patients who had preoperative pain and myelopathy improved
      at least one grade in 17 patients (47%; p < 0.05). Twenty-six surviving patients
      (72%) were followed for more than 24 months and stable, osseous union occurred in
      97%. These results show that extensive, multilevel anterior decompression and
      stabilization using fibular allograft can be achieved with a perioperative
      mortality and major morbidity rate of 22% and with significant improvement in
      pain and myelopathy.

PMID- 9171179
TI  - Chymopapain-induced reduction of proinflammatory phospholipase A2 activity and
      amelioration of neuropathic behavioral changes in an in vivo model of acute
      sciatica.
AB  - The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis
      remains obscure. Radiographic studies suggest that chymopapain does not alter
      disc fragment size acutely; nonetheless, patients often report symptom resolution
      within a few days, even hours, of treatment. The authors postulate that, in
      addition to its chemonucleolytic action, chymopapain may possess antiinflammatory
      properties. To test this hypothesis, the authors assessed the ability of
      chymopapain to modulate the activity of the proinflammatory enzyme phospholipase
      A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory
      neuropathy in an in vivo model of sciatica. Thirty-nine male Fischer rats were
      randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone,
      or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation
      with loose chromic gut suture to induce inflammatory mononeuropathy. The animals
      were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7
      (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to
      determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On
      Day 7, three animals from each group were killed to assess PLA2 activity prior to
      treatment. The remainder were given a single infusion of saline, betamethasone
      (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14,
      the remaining animals were killed and their sciatic nerves were removed. The
      tissue was homogenized and the PLA2 activity was determined using
      [14C]arachidonate-labeled Escherichia coli phospholipid membrane as a substrate.
      Lipids were extracted and separated by thin-layer chromatography. All animals
      developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72
      hours postoperatively; these included gait disturbance, flexion deformity, and
      hyperalgesia of the involved hindlimb. The degree of mechanical and thermal
      hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal
      hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the
      betamethasone- and chymopapain-treated groups than in the saline-treated controls
      (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs.
      betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day
      0) was 11.6 +/- 4.9 nmol phospholipid hydrolyzed per minute per milligram of
      protein. The PLA2 activity at Day 7 was 74.4 +/- 18.2 (ligated side) and 21.2 +/-
      11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain-
      (47.8 +/- 12.3) and betamethasone- (39.7 +/- 9.5) treated groups compared with
      the saline control group (62.3 +/- 11.2), (saline- vs. chymopapain-treated groups
      p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity
      in nonligated specimens was 18.6 +/- 10.1. These data indicate that chymopapain
      exhibits antiinflammatory properties in vivo, reducing PLA2 activity and
      ameliorating mechanical hyperalgesia in this model of inflammatory sciatic
      neuropathy.

PMID- 9171181
TI  - Development of a dural substitute from synthetic bioabsorbable polymers.
AB  - A new bioabsorbable composite sheet was developed to provide a substitute for the
      dura mater and was evaluated histologically and biomechanically using rats and
      rabbits. This composite, composed of two L-lactic acid-epsilon-caprolactone (50%
      L-lactic acid, 50% epsilon-caprolactone) copolymer films and a poly(glycolic
      acid) nonwoven fabric, displayed good mechanical properties and was completely
      absorbed 24 weeks after implantation in the back of rats. Histological evaluation
      of the composite sheet was undertaken by implanting it in 31 rabbits with dural
      defects and examining the sites of implantation 2 weeks to 26 months later. No
      infection, cerebrospinal fluid leakage, evidence of convulsive disorders,
      significant adhesion to underlying cortex, or calcification was noticed in any
      cases. In addition, the regenerated duralike tissue had a high pressure-resistant
      strength 2 weeks after implantation. The authors conclude that this new
      bioabsorbable composite sheet can be successfully used as a dural substitute.

PMID- 9171180
TI  - Reduction of spinal cord injury by administration of iloprost, a stable
      prostacyclin analog.
AB  - To investigate whether iloprost, a stable analog of prostacyclin, is useful for
      the prevention of posttraumatic spinal cord injury, we examined its effects on
      compression trauma-induced spinal cord injury in rats. Spinal cord injury was
      induced by applying a 20-g weight for 20 minutes to the spinal cord at the level
      of T-12, resulting in motor disturbances in the hindlimbs. These motor
      disturbances, evaluated using Tarlov's index, were markedly attenuated in rats
      with nitrogen mustard-induced leukocytopenia. Administration of iloprost also
      attenuated the motor deficits. Histological examination revealed that
      intramedullary hemorrhages observed 24 hours after trauma were significantly
      attenuated in leukocytopenic animals and in animals that received iloprost. The
      accumulation of leukocytes at the site of trauma, evaluated by measuring tissue
      myeloperoxidase activity, significantly increased with time following the trauma,
      peaking at 3 hours postinjury. Spinal cord myeloperoxidase activity in sham
      operated animals did not increase postoperatively. Leukocyte depletion and
      administration of iloprost reduced the accumulation of leukocytes in the damaged
      spinal cord segment 3 hours posttrauma. These findings indicate that iloprost
      attenuates motor disturbances induced by spinal cord trauma and that its
      therapeutic efficacy can be partly explained by its inhibition of leukocyte
      accumulation at the traumatized site.

PMID- 9171182
TI  - Inadequate PAX-1 gene expression as a cause of agenesis of the thoracolumbar
      spine with failure of segmentation. Case report.
AB  - An unusual case with absence and "fusion" of several thoracic and lumbar
      vertebral bodies leading to a severe thoracolumbar kyphos is presented. Late
      onset neurological deterioration occurred due to spinal cord compression, which
      was treated with anterior decompression. Although several mechanisms for the
      development of these extensive and rare abnormalities have been proposed, the
      cause in humans remains unknown. An embryological basis is presented in the light
      of recent advances in molecular genetics, which show that abnormal notochordal
      signals and Pax-1 gene expression can produce an experimental phenotype very
      similar to the one in the patient described here. Thus it is suggested that
      faults in these early developmental processes may be, at least in part,
      responsible for the development of such extensive anomalies.

PMID- 9171183
TI  - Calcium carbonate apatite deposition in the cervical spine with associated
      vertebral destruction. Case report.
AB  - This 52-year-old woman developed crystal deposition disease involving the
      cervical vertebrae. She presented with symptomatic spinal cord compression
      secondary to extensive calcified lesions in the posterior elements of the
      cervical spine. Surgical decompression with posterior fusion was performed.
      Histological examination showed hardened deposits of calcium carbonate involving
      the soft tissue, and dissolution of the vertebral bone trabeculae. There was no
      inflammatory response to these deposits. One year postoperatively the patient
      developed severe pulmonary disease associated with the collagen-vascular
      disorder, scleroderma (calcinosis, Raynaud's phenomenon, esophageal hypomotility,
      sclerodactyly, and telangiectasia [CREST] syndrome). Calcium carbonate deposition
      disease represents an unusual clinical entity that is possibly associated with
      scleroderma or other collagen-vascular diseases, and it is distinct from
      ligamentum flavum calcification, calcium pyrophosphate deposition disease, and
      hydroxyapatite deposition disease.

PMID- 9171184
TI  - Synovial cyst and degeneration of the transverse ligament: an unusual cause of
      high cervical myelopathy. Case report.
AB  - A case of cystic degeneration of the transverse ligament located posteriorly to
      the dens and causing compression to the lower medulla and upper cervical spinal
      cord is reported. The clinical, pathological, and radiological findings are
      described and compared to the literature to characterize this syndrome more
      fully. The advantages of a posterolateral surgical approach are stressed.

PMID- 9171185
TI  - Rotational occlusion of the vertebral artery caused by transverse process
      hyperrotation and unilateral apophyseal joint subluxation. Case report.
AB  - The authors describe transverse process hyperrotation and unilateral apophyseal
      joint subluxation as a novel mechanism of rotational vertebral artery (VA)
      occlusion. The patient, a 56-year-old man, complained of episodic bilateral
      blindness when rotating his head more than 90 degrees to the right. Plain
      cervical x-ray films showed spondylotic osteophytes of the right C4-5
      uncovertebral portion. Dynamic angiography revealed right VA occlusion at C4-5
      and left VA occlusion at C1-2 with head rotation to the right. It was
      demonstrated on three-dimensional images constructed from computerized tomography
      scans that C-4 transverse process hyperrotation compressed the right VA against
      the apex of the C-5 subluxating superior articular process via the inner surface
      of the transverse process anterior root (processus costarius) rather than the
      osteophytes. It is also proposed that the true site of occlusion is different
      from that observed in angiographic studies.

PMID- 9171186
TI  - Saphenous vein graft bypass of the sigmoid sinus and jugular bulb during the
      removal of glomus jugulare tumors. Report of two cases.
AB  - Glomus jugulare tumors always invade the jugular bulb and sigmoid sinus, making
      it difficult to resect these tumors totally without sacrificing the involved
      sinus. Although the sinus can be sacrificed safely in most patients, a few
      patients will have serious consequences. Reconstruction of the jugular bulb using
      a saphenous vein graft may enable tumor resection in these patients without
      complications. The authors describe two cases of saphenous vein grafting used to
      bypass the sigmoid sinus. The first case is that of a 61-year-old man with a
      glomus jugulare tumor that invaded the dominant sigmoid sinus, which was poorly
      collateralized. Temporary occlusion of the sinus during surgery caused a 15-mm Hg
      increase in intrasinus pressure, without brain swelling or changes in evoked
      potentials. A saphenous vein graft was used to bypass the sigmoid sinus and
      jugular bulb and to allow for total tumor removal. The patient had a good
      outcome. The second case is that of a 41-year-old man with a left glomus jugulare
      tumor and another smaller tumor on the opposite, dominant sinus. The left glomus
      jugulare tumor was resected via a two-stage procedure. A saphenous vein graft was
      used to reconstruct the left sigmoid sinus because of the presence of
      contralateral disease, with the potential for bilateral sigmoid sinus occlusion.
      An evaluation of the venous collateral circulation during jugular foramen surgery
      and the prevention of complications are also discussed.

PMID- 9171187
TI  - Multifocal noninfectious granulomatous encephalitis in a child. Case report.
AB  - This 9-year-old boy presented with a multifocal, apparently noninfectious
      granulomatous process involving the central nervous system. Despite gross-total
      excision of the large left temporal lesion, it recurred after surgery.
      Serological studies and cultures failed to demonstrate an infectious agent, and
      histopathological investigation showed a nonspecific granulomatous process
      without vasculitis. The patient underwent a second craniotomy and was given
      corticosteroid therapy. There has been no recurrence during 3 years of follow-up
      review, the last year of which included no course of steroid medications. The
      case is presented as a noninfectious idiopathic granulomatous encephalitis that
      is responsive to surgery and corticosteroid therapy. To the authors' knowledge,
      it is the first reported case of its kind.

PMID- 9171188
TI  - Craniopharyngioma arising de novo in middle age. Case report.
AB  - The authors report the case of a 55-year-old woman who developed a symptomatic
      craniopharyngioma within 2 years of obtaining a normal magnetic resonance image
      of her brain. Craniopharyngiomas are histologically benign tumors. They are
      thought to arise from embryonic remnants of Rathke's pouch and sac and to
      manifest themselves clinically after a steady growth that commences in fetal
      life. To the authors' knowledge, this is the first report that documents a tumor
      arising de novo in the sixth decade of life. This report appears to challenge the
      concept of the origin and natural history of craniopharyngiomas.

PMID- 9171189
TI  - Solitary fibrous tumor of the meninges. Case report and review of the literature.
AB  - The authors present the case of a left frontal solitary fibrous tumor of the
      meninges. The gross appearance of the tumor was very similar to that of a
      fibroblastic meningioma. Histological examination showed a mixture of spindle
      shaped and round cells arranged in a collagen matrix. Immunohistochemical
      staining of the tumor demonstrated diffuse positive staining for CD34 and
      vimentin. The tumor displayed no positive staining for markers of muscle,
      epithelial, glial, or neurocrest differentiation or for estrogen and progesterone
      receptors. The MIB-1 labeling index (the percentage of positive staining tumor
      cell nuclei), a marker of cellular proliferation, was 1.1%. Ultrastructural
      studies support attributing a mesenchymal, rather than meningothelial, nature to
      the tumor. A differential diagnosis is discussed and a review of the literature
      on these rare tumors is presented.

PMID- 9171190
TI  - Selective cochlear neurotomy in the cerebellopontine cistern using
      electrophysiological monitoring in a patient with intractable tinnitus. Case
      report.
AB  - Selective cochlear neurotomy for intractable tinnitus is quite difficult to
      perform because there is no way to approach the cochlear nerve without
      interfering with other neural structures. The authors successfully performed
      selective cochlear neurotomy in the cerebellopontine cistern in a patient with
      persistent intractable high-pitched tinnitus, but with normal hearing and
      vestibular functions, by monitoring cochlear nerve compound action potentials and
      auditory brainstem responses. The procedure is a very simple and safe technique
      for the treatment of intractable tinnitus. Although this destructive procedure is
      the last choice of treatment, it can be justified in patients who have poor
      hearing and severe tinnitus in spite of normal vestibular functions. The
      procedure may also be applied in some rare cases such as that of the present
      patient whose quality of life was markedly reduced because loud tinnitus
      prevented him from hearing anything with the affected ear even though his hearing
      and vestibular functions were normal.

PMID- 9171191
TI  - Direct brainstem recording of auditory evoked potentials during vestibular
      schwannoma resection: nuclear BAEP recording. Technical note and preliminary
      results.
AB  - The usefulness of intraoperative monitoring in cerebellopontine angle surgery
      should be improved by obtaining faster and stronger brainstem auditory evoked
      potential (BAEP) responses. A new technique of direct recording at the brainstem
      has been developed, which is applicable to all tumor sizes. By placing a
      retractor with electrodes attached to its tip at the cerebellomedullary junction,
      the authors have recorded BAEP amplitudes that are 10 times greater than those
      recorded using the conventional technique. Only small sampling numbers (64-256
      recordings) are required and are obtained in 5 to 15 seconds. The technique has
      been applied successfully in 34 patients who underwent vestibular schwannoma
      resections. It has also been tested in patients with intrameatal-extrameatal
      meningiomas and in those with vascular compressive disorders; there have been no
      false results. The advantages of this new technique are: 1) identification of
      BAEP components is easier and faster; 2) reliable BAEP responses are obtained in
      some cases in which conventional BAEP responses are lost or severely deformed;
      and 3) BAEP response deterioration and improvement are recognized earlier than
      would occur using the conventional technique. This last advantage provides the
      surgeon with a useful warning at a stage of surgery at which BAEP changes are
      still temporary and can be reversed. This method is different from other trials
      of intradural BAEP recordings in three respects: its use is not limited to
      particular tumor sizes; there is no interference with the surgical process; and,
      most important, the obtained responses correlate well with those of conventional
      BAEP responses, probably because the recording site is in the vicinity of the
      anterior cochlear nucleus. In conclusion, the chances of useful monitoring
      feedback with adequate adaptation of the microsurgical strategy are improved
      considerably.

PMID- 9171192
TI  - Ventriculofemoroatrial shunt: a viable alternative for the treatment of
      hydrocephalus. Technical note.
AB  - Children with shunted hydrocephalus often have a myriad of other medical
      conditions. When these concomitant problems involve the pleura, peritoneum,
      and/or the venous system, placement of the distal catheter may prove to be
      problematic. This report presents preliminary results in three hydrocephalic
      children following ventriculofemoroatrial shunt placement. The peritoneal and
      pleural cavities in each of these children were compromised and there was no
      vascular access into the superior vena cava due to intercurrent disease. An
      alternative technique for ventriculoperitoneal shunt placement was performed via
      the femoral vein. Fluoroscopic guidance was used to confirm the intraatrial
      position of the distal end of the shunt catheter. Follow-up review to date shows
      no complications. This newly described technique provides a feasible alternative
      to distal shunt catheter placement in patients in whom more traditional sites are
      unavailable.

PMID- 9171193
TI  - Serial magnetic resonance imaging of delayed radiation necrosis treated with
      dexamethasone. Case illustration.

PMID- 9171194
TI  - White blood cell count and mortality.

PMID- 9171195
TI  - Minimalist versus maximalist approach to the degenerative spine.

PMID- 9171197
TI  - Amygdalohippocampectomy.

PMID- 9171196
TI  - Pentobarbital and venous oxygenation.

PMID- 9171198
TI  - Transpetrosal approach and sinus division.

PMID- 9171199
TI  - Detection and interpretation of lysergic acid diethylamide results by immunoassay
      screening of urine in various testing groups.
AB  - A total of 2259 urine samples were assayed for lysergic acid diethylamide (LSD)
      using radioimmunoassay (RIA, Coat-a-Count, Diagnostics Products) and a premarket
      cloned enzyme donor immunoassay (CEDIA, Boehringer Mannheim). Urine samples were
      obtained from patients admitted to the emergency room, patients in drug
      rehabilitation programs, and adults and juveniles in criminal probation programs.
      An overall incidence of positive results was 0.80% for CEDIA (500-pg/mL cutoff)
      and 0.89% and 0.18% for RIA at cutoffs of 250 and 500 pg/mL, respectively. Of the
      CEDIA-positive samples, only 17 and 11% were positive by RIA at 250 and 500
      pg/mL, respectively, whereas among RIA-positive samples, only 10% of those > 250
      pg/mL and only 25% of those > 500 pg/mL were positive by CEDIA. Moreover, only 2
      of 25 of samples positive by one of these screening assays were confirmed by gas
      chromatography-mass spectrometry (GC-MS). It is likely that discrepancies in
      results between immunoassays are due to differences in antibody specificities
      used to detect LSD metabolites. In addition, immunoassays may be more sensitive
      than GC-MS for detecting LSD use as current confirmation assays are targeted
      towards detection of the parent drug only. The interpretation of results for LSD
      analysis must be made with knowledge of the limitations for each assay.

PMID- 9171200
TI  - Selective determination of amitriptyline and nortriptyline in human plasma by
      HPLC with ultraviolet and particle beam mass spectrometry.
AB  - A selective, sensitive, and reliable method was devised to determine
      concentrations of amitriptyline and its major metabolite, nortriptyline, in human
      plasma using high-performance liquid chromatography (HPLC) combined with UV and
      particle beam mass spectrometry (PBMS). Amitriptyline and nortriptyline were
      effectively extracted in a three-step solvent extraction procedure. Imipramine
      was used as the internal standard (IS). Amitriptyline, nortriptyline, and the IS
      were clearly separated by HPLC on a silica column with the mobile phase of
      acetonitrile-0.1 M ammonium acetate (94:6, v/v). The calibration curves were
      linear in the concentration range of 10-1000 ng/g for both compounds with UV and
      PBMS detections. The lower limits of detection were 5 ng/g for amitriptyline and
      10 ng/g for nortriptyline with UV detection and 2 ng/g for amitriptyline and 5
      ng/g for nortriptyline with PBMS detection. The absolute recoveries were 58% for
      amitriptyline and 47% for nortriptyline at a concentration of 50 ng/g. This
      method proved most useful in accurately identifying amitriptyline and
      nortriptyline in tissues from an autopsied individual.

PMID- 9171202
TI  - A unique metabolite of nimesulide.
AB  - Nimesulide is a nonsteroidal anti-inflammatory drug recently detected in equine
      blood and urine samples taken at the race track. The detection of the drug in a
      blood sample led to the identification of an unknown thin-layer chromatographic
      (TLC) spot in track urine samples as a metabolite of nimesulide. Characterization
      of the unknown TLC spot and comparison with the synthesized compound shows that
      the unknown TLC spot is a previously unreported equine metabolite of nimesulide.
      The metabolite was identified as resulting from the reduction of the nitro group
      on nimesulide to an amino group. This reduced nitro metabolite (4-amino-2-phenoxy
      methanesulfonanilide) is a major metabolite of nimesulide in the equine.

PMID- 9171201
TI  - Detection of flunixin in greyhound urine by a kinetic enzyme-linked immunosorbent
      assay.
AB  - A two-step kinetic enzyme-linked immunosorbent assay was developed to detect the
      presence of flunixin in the urine of greyhound dogs. The assay system was
      developed using polyclonal antiflunixin antisera, a rabbit albumin-flunixin
      conjugate adsorbed onto polystyrene microtiter strips, and flunixin reference
      standards for calibration. The assay parameters were optimized and the
      performance characteristics were determined. The quantitative intra- and inter
      run precisions (%CV) of the analysis of replicate (n = 10) flunixin-spiked urine
      samples were 9.9-12.5% and 10.2-13.6%, respectively. The linear dynamic range was
      1-100 ng/mL, and the quantitative accuracy, as determined by calculation of
      percent error of measured flunixin in flunixin-spiked drug-free greyhound urine,
      was -16% to +14% over this range. The I50 of the ELISA was 17.3 ng/mL. The limit
      of detection was 25 ng/mL in greyhound urine. The reactivity in the assay system
      relative to flunixin (100%) was 147% for flunixin glucuronide, 25% for clonixin,
      and 5% for niflumic acid. The ELISA was capable of detecting total flunixin for
      up to 72 h in dogs administered flunixin at 0.55 mg/kg orally and up to 96 h in a
      dog that was administered flunixin at 1.0 mg/kg orally.

PMID- 9171203
TI  - A rapid, specific, and sensitive method for the determination of acetylation
      phenotype using dapsone.
AB  - An original, simple, specific, and rapid high-performance liquid chromatography
      assay for the determination of dapsone and monoacetyldapsone in human plasma is
      presented. The procedure consists of extracting the drugs and the internal
      standard (phenacetin) from 1 mL plasma with ethyl ether at alkaline pH. A liquid
      chromatograph equipped with a reversed-phase 5-microm C8 analytical column was
      used. The drugs were eluted with a mixture of water and methanol (70:30, v/v).
      Flow rate and wavelength were set at 1 mL/min and 286 nm, respectively. The
      precision, linearity, and limit of quantitation of the method were within
      acceptable limits. The method was considered adequate and has been used for the
      determination of the acetylator phenotype in population studies.

PMID- 9171204
TI  - Detection of 2-amino-5-chloropyridine in urine as a parameter of zopiclone
      (Imovane) intake using HPLC with diode array detection.
AB  - A qualitative screening technique was developed for the detection of 2-amino-5
      chloropyridine, a newly identified decomposition product of zopiclone and
      metabolites after alkaline hydrolysis of urine samples. The method was elaborated
      using a standard operation procedure (Merck Tox Screening System), combining a
      solid-phase extraction with reversed-phase high-performance liquid chromatography
      and diode array detection. The limit of detection, expressed as zopiclone
      concentrations in spiked urine, was found to be 0.5 microg/mL. Field urine
      samples from a volunteer were positive for 2-amino-5-chloropyridine until 16 h
      after ingestion of one therapeutic dose of Imovane (7.5 mg zopiclone).

PMID- 9171205
TI  - Evaluation of the CEDIA DAU assays and the AxSym system for the analysis of
      cannabinoids in whole blood.
AB  - The Microgenics CEDIA DAU (EIA) and the Abbott AxSym system (FPIA) cannabinoids
      assays were evaluated for their combined effectiveness in the analysis of
      cannabinoids in whole blood. Blood samples were treated with acetone, evaporated,
      and reconstituted, and the supernatant was analyzed by the EIA cannabinoids
      assay. Blood samples determined positive by EIA were then treated with
      acetonitrile and sodium sulfate, and the resultant protein-free supernatant was
      analyzed using the FPIA cannabinoids assay. A total of 98 blood samples
      determined to be presumptively positive by both EIA and FPIA were further
      analyzed for the presence of 11-nor-carboxy-delta9-tetrahydrocannabinol-9
      carboxylic acid (THCCOOH). All 98 blood samples could be confirmed for the
      presence of THCCOOH by gas chromatography-mass spectrometry (GC-MS) at
      concentrations greater than the 10 ng/mL cutoff. The GC-MS results were found to
      correlate significantly better with those of the FPIA cannabinoids assay (r =
      0.75) than with EIA (r = 0.22). Procedures for the rapid analysis of whole blood
      for cannabinoids using CEDIA DAU reagents and the AxSym system are presented.

PMID- 9171207
TI  - A fatal case of amlodipine poisoning.
AB  - A fatal case attributed to amlodipine intoxication is presented. The deceased was
      a 15-year-old girl who allegedly ingested 14 10-mg Istin tablets. Amlodipine
      concentration in peripheral blood was determined (2.7 mg/L) and was compared with
      published therapeutic and toxic data for amlodipine and some other
      dihydropyridine calcium channel-blocking agents. Amlodipine concentrations in
      liver, blood, and stomach contents were also determined.

PMID- 9171206
TI  - A fatality due to alprazolam intoxication.
AB  - Alprazolam is one of the most widely prescribed benzodiazepines in the United
      States. It is generally considered a safe and effective drug for the treatment of
      anxiety disorders and panic attacks. Few overdoses that are due to the sole
      ingestion of alprazolam have been reported. This paper documents a fatality due
      to alprazolam intoxication and describes the distribution of alprazolam and an
      active metabolite, alpha-hydroxyalprazolam, in tissues obtained at autopsy.
      Qualitative identification of the drugs was achieved by full-scan gas
      chromatography-mass spectrometry, and quantitative analysis was performed by high
      performance liquid chromatography. High concentrations of alprazolam were found
      in all specimens analyzed, but the metabolite was detected only in subclavian
      blood, urine, bile, and liver. A postmortem heart blood alprazolam concentration
      of 2.1 mg/L is the highest reported in the literature to date.

PMID- 9171208
TI  - Tissue distribution of trichloroethylene and its metabolites in a forensic case.
AB  - A fatality that was due to the ingestion of the halogenated solvent
      trichloroethylene is presented. The decedent was a 43-year-old male who was found
      dead at his home. Screening of the blood and stomach contents with the enzyme
      multiplied immunoassay technique and radioimmunoassay demonstrated the presence
      of ethanol, amphetamine-like compounds, caffeine, cotinine, and acetaminophen.
      These compounds were present in toxicologically irrelevant concentrations as
      confirmed by thin-layer chromatography, high-performance liquid chromatography,
      and gas chromatography (GC). The Fujiwara reaction was performed on all available
      matrices, and it revealed the presence of chlorinated hydrocarbons in high
      concentrations. A specific GC method with electron capture detection allowed the
      quantitation of trichloroethylene and its metabolites trichloroethanol and
      trichloroacetic acid in different matrices. GC with Fourier-transform infrared
      detection was used for the confirmation of the identity of trichloroethylene.

PMID- 9171209
TI  - A fatal case of betaxolol poisoning.
AB  - We report the first case in the literature of fatal betaxolol (Kerlone) self
      poisoning. After a single-step liquid-liquid alkaline extraction, betaxolol was
      identified by a high-performance liquid chromatographic-diode array detection
      screening procedure and then quantitated in cardiac blood, heart, brain, muscle,
      spleen, stomach contents, duodenum contents, liver, and kidney. The blood
      betaxolol concentration was 36 mg/L.

PMID- 9171210
TI  - Concentrations of heroin, 06-monoacetylmorphine, and morphine in a lethal case
      following an oral heroin overdose.
AB  - A case of lethal overdose by heroin ingestion is presented. The concentrations of
      drugs were measured several hours after death. Heroin, 06-monoacetylmorphine, and
      morphine were identified and quantitated in blood, urine, and gastrointestinal
      contents by gas chromatography-mass spectrometry and high-performance liquid
      chromatography. Concentrations of heroin, 06-monoacetylmorphine, and morphine
      were 109, 168, and 1140 ng/mL, respectively, in blood and 17, 12, and 425 ng/g,
      respectively, in gastrointestinal content. In urine, however, only morphine was
      detected at 3650 ng/mL.

PMID- 9171211
TI  - Tissue distribution of amphetamine isomers in a fatal overdose.
AB  - A young man (22 years old) died of a cardiorespiratory arrest a few hours
      following admission to the emergency department of a hospital. He was found lying
      seriously ill in the parking lot of a dance club. Screening of postmortem blood
      and urine with enzyme multiplied immunoassay (EMIT) detected only amphetamines,
      caffeine, and cotinine. Further screening of blood, urine, and stomach contents
      with thin-layer chromatography (TLC) and high-performance liquid chromatography
      (HPLC) was negative for all three matrices. Specific conditions for amphetamines
      were used for the gas chromatographic (GC) screening (GC-mass spectrometric [MS]
      and GC-nitrogen-phosphorus detection). This resulted in the preliminary
      identification of amphetamine in both blood and urine. Confirmation of the
      presence of amphetamine in all available postmortem specimens was provided by
      mass and infrared spectral data (GC-MS and GC-Fourier transform infrared
      spectrometry) after derivatization. Quantitative results and differentiation
      between the enantiomers of amphetamine were obtained after chiral derivatization.
      The calculated concentrations disclosed amphetamine ingestion as the cause of
      this fatality.

PMID- 9171212
TI  - A procedure to overcome interferences caused by the adulterant "Klear" in the GC
      MS analysis of 11-nor-delta9-THC-9-COOH.

PMID- 9171213
TI  - Evaluation of the Rapidrog Cannabis noninstrumental immunoassay.

PMID- 9171214
TI  - Reducing false-negative tests in urinary drugs-of-abuse screening.

PMID- 9171215
TI  - Large amounts of drugs may considerably influence the peak areas of their
      coinjected deuterated analogues measured with APCI-LC-MS.

PMID- 9171216
TI  - HIV type 1 coreceptors, neutralization serotypes, and vaccine development.

PMID- 9171217
TI  - Quantitation of target molecules from polymerase chain reaction-based limiting
      dilution assays.
AB  - Polymerase chain reaction-based limiting dilution assays (PLDAs), commonly called
      end-point dilutions, are frequently used to quantify the copy numbers of human
      immunodeficiency virus (HIV) and other viruses in biological samples; however,
      the way in which these assays are done, and the mathematical method used to
      estimate copy numbers, vary from laboratory to laboratory. Here, we describe a
      statistical method for estimating the number of copies and the associated
      standard error of the estimate, using a PLDA. The copy number is estimated by the
      value that maximizes the goodness of fit between the observed numbers of negative
      reactions and the expected numbers of negative reactions (the latter estimated
      using a Poisson probability distribution) as measured by the chi2 statistic. The
      method described here also takes into account user-specified probabilities of
      obtaining a false-positive or a false-negative PCR result, a feature that is not
      generally available with other limiting dilution estimation procedures. QUALITY,
      a computer program that implements the estimation strategy, is also described.
      Simulations illustrate the efficiency of estimation with different numbers of PCR
      amplifications conducted at each dilution, and different dilution factors.
      Finally, a simple strategy for more efficient assays is proposed.

PMID- 9171218
TI  - Isolation and characterization of two divergent infectious molecular clones of
      HIV type 1 longitudinally obtained from a seropositive patient by a progressive
      amplification procedure.
AB  - Isolation of infectious molecular clones has been valuable to our understanding
      of HIV-1-induced pathogenesis. Two infectious molecular clones of HIV-1 were
      isolated longitudinally from a seropositive subject at different stages of the
      disease, using a standard bacteriophage lambda vector and a novel progressive
      amplification procedure. We found the progressive amplification procedure was
      simpler and more specific than the conventional plaque hybridization assay. The
      two infectious HIV-1 clones had distinct cell tropism and cytopathic properties.
      The HIV-1 clone obtained at the asymptomatic stage of the disease was macrophage
      tropic and had a non-syncytium-inducing property. In contrast, the HIV-1 clone
      obtained at the stage of AIDS development was dual tropic for T cells and
      macrophages and induced syncytia. A detailed analysis of the restriction sites of
      the two clones showed 9 of 21 sites to be unique. These unique restriction sites
      were predominantly localized in the envelope region. Furthermore, the nucleotide
      sequence analysis of the entire gp120 region supported the results from the
      restriction analysis and showed that these two clones are closely related, and
      the differences are restricted to the variable domains. The difference in amino
      acid sequences in the V3 region may explain the observed differences in T cell
      tropism and syncytium-inducing properties. Availability of two distinct
      infectious molecular clones from the same patient at different stages of the
      disease may be useful in studies on the mechanism of HIV-1 pathogenesis.

PMID- 9171219
TI  - Structure and origin of HIV type 1 DNA in persistently infected B lymphoblastoid
      cell lines.
AB  - The Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) can
      coinfect resting B cells, leading to EBV-carrying lymphoblastoid cell lines
      (LCLs) persistently infected with HIV-1. LCLs established from coinfected
      peripheral blood lymphocytes (PBLs) differed from LCLs derived from HIV-1
      infected cell lines, in that the majority if not all of the cells expressed gp120
      and a high percentage produced infectious HIV-1 after continuous passage for 6-9
      months. Restriction analysis of the putative HIV-1 provirus revealed that
      persistently infected LCLs carried variable copies of primarily unintegrated
      circular and/or linear forms of HIV-1 DNA. This extrachromosomal location is
      strikingly different from that of the one to three copies of integrated proviral
      DNA deleted in persistently infected T cell and monocytic cell lines. Anti-gp120
      monoclonal antibody and 3'-azido-3'-deoxythymidine (AZT) inhibited HIV-1
      expression and reduced HIV-1 DNA copy number in persistently infected LCLs,
      supporting the hypothesis that unintegrated HIV-1 DNA accumulates primarily as a
      result of superinfection. We propose that the extrachromosomal location of the
      HIV-1 DNA contributes to the semipermissive nature of B cell infection by HIV-1.

PMID- 9171220
TI  - Abortive infection in HeLaCD4 cells by a primary HIV type 1 isolate: implications
      for differential host cell tropism.
AB  - The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants
      from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI)
      strains is associated with disease progression in infected individuals. HIV89.6
      is a primary isolate with a transitional phenotype: like M-tropic strains it
      replicates in primary macrophages and lymphocytes but not in most transformed
      cells, yet it is also syncytium inducing. We have shown that HIV89.6 can utilize
      both the M-tropic and T-tropic cofactors CCR-5 and CXCR-4, respectively, in
      conjunction with CD4 for fusion and entry into otherwise nonpermissive nonhuman
      cells. To better understand the nature of restricted HIV89.6 infection of
      transformed cells, we analyzed its interaction with CD4-expressing transformed
      human HeLaCD4-LTR/beta-Gal cells, which contain the beta-galactosidase gene
      linked to the HIV-1 LTR. Here we show that HIV89.6 enters these cells and
      undergoes reverse transcription and integration. Furthermore, HIV89.6 induces LTR
      driven beta-galactosidase expression, indicating Tat-dependent trans-activation,
      in a similar number of cells as the permissive T-tropic/SI isolate HIV(HXB).
      Acute infection with HIV89.6, however, produces markedly lower levels of p24
      antigen and infectious virus per trans-activation-positive cell than HIV(HXB). In
      contrast, transfection results in high levels of expression for both viruses but
      HIV89.6 still fails to establish spreading infection. HIV89.6 is also blocked
      after entry in two other nonpermissive cell lines, SUP-T1 and U937. HIV89.6
      arrest in HeLaCD4-LTR/beta-Gal cells at a stage subsequent to entry, reverse
      transcription, integration, and Tat expression is a novel level at which HIV-1
      strain- and cell-specific restrictions define host cell tropism. These studies
      emphasize that complex patterns of tropism are determined by the interplay of
      permissive or restricted virus-cell interactions at multiple steps in the
      replication cycle.

PMID- 9171221
TI  - Apoptosis in HIV-infected individuals is an early marker occurring independently
      of high viremia.
AB  - We have analyzed the immunoreactivity of peripheral blood mononuclear cells by
      determining the proliferative response to four mitogens, one superantigen, and
      one recall antigen together with the occurrence of activation-induced apoptosis
      from 213 HIV-1-seropositive individuals from all stages of infection. The
      expected decline of immunoreactivity observed with time after infection
      correlated with disease progression and the loss of CD4 cells. Apoptosis was
      already detectable at the early stages of infection and increased only slightly
      with disease progression. In analyzing 13 patients with high and low apoptosis
      rates we observed no correlation to HIV-1 viremia. Our results argue that mitogen
      induced apoptosis occurs in both infected and noninfected T cells and can be
      detected before mitogenic responsiveness is reduced.

PMID- 9171222
TI  - Interleukin 6 and AIDS-associated Kaposi's sarcoma: a nested case control study
      within the Multicenter AIDS Cohort Study.
AB  - Since the beginning of the AIDS epidemic, there has been considerable research on
      the etiology of Kaposi's sarcoma (KS) among HIV-infected individuals. A number of
      studies have confirmed that HIV or HIV-encoded products can interact with human
      cells to induce the production of cytokines, including interleukin 6 (IL-6). In
      vitro observations have indicated that AIDS-KS cells can produce significant
      levels of IL-6 and also respond to this cytokine. Preliminary data suggested that
      IL-6 may be elevated among HIV-infected individuals that subsequently develop
      AIDS-KS. The objective of this study was to determine if elevated levels of IL-6
      are associated with an increased incidence of AIDS-KS compared to other AIDS
      defining illnesses such as opportunistic infections (OIs). Serum IL-6 levels were
      determined by ELISA in frozen sera collected from participants in the Multicenter
      AIDS Cohort Study (MACS) at 6 months prior to AIDS diagnosis, in 73 cases (AIDS
      KS), and 152 controls (OI). Elevated IL-6 levels were more prevalent among men
      with AIDS-OI than those with AIDS-KS: crude odds ratio (OR), 0.4 (95% CI, 0.2
      0.9). Models of multivariate logistic regression were used to study potential
      confounders. Sexual behavior variables did not seem to confound the association
      between IL-6 and AIDS-KS. The higher prevalence of IL-6 among controls could be
      explained by the association of higher levels of IL-6 with lower levels of CD4 T
      cell number. IL-6 may be a marker of severe immune dysfunction among HIV-infected
      individuals.

PMID- 9171223
TI  - Efficacy, pharmacokinetics, and in vivo antiviral activity of UC781, a highly
      potent, orally bioavailable nonnucleoside reverse transcriptase inhibitor of HIV
      type 1.
AB  - A series of compounds related to oxathiin carboxanilide has been identified as
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1, and structure
      activity relationships have been described (Buckheit RW, et al.: Antimicrob
      Agents Chemother 1995;39:2718-2727). Three new analogs (UC040, UC82, and UC781)
      inhibited laboratory and clinical isolates of HIV-1, including isolates
      representative of the various clades of HIV-1 found worldwide, in both
      established and fresh human cells. Virus isolates with the amino acid changes
      L100I, K103N, V106I, and Y181C in the reverse transcriptase were partially
      resistant to these compounds. However, UC781 inhibited these virus isolates at
      low nontoxic concentrations, presenting a broad in vitro therapeutic index. As
      with other NNRTIs, each of the compounds synergistically interacted with AZT to
      inhibit HIV-1 replication. UC781 possesses a favorable pharmacokinetic profile in
      mice with a high level of oral bioavailability. Plasma concentrations reached
      maximum levels within 2 to 4 hr of oral administration and remained in excess of
      those required for in vitro anti-HIV activity for at least 24 hr after a single
      oral dose. When evaluated in a murine hollow fiber implant model of HIV
      infection, UC781 dosed orally or parenterally was able to suppress HIV
      replication completely in this model system, providing evidence of the in vivo
      efficacy of the compound.

PMID- 9171224
TI  - The construction and evaluation of SIV/HIV chimeras that express the envelope of
      European HIV type 1 isolates.
AB  - The molecular construction of SIV/HIV-1 chimeric viruses (or SHIVs), provides a
      means of infecting macaques with immunodeficiency viruses that express the
      envelope protein of HIV-1. However, to date, most SHIVs produced express the
      envelope of isolates of HIV-1 that have been passaged repeatedly in T cell lines.
      We have taken SHIV-4 and replaced an NheI-AvrII fragment that encompasses the
      gp120 region and the extracellular portion of gp41 with the equivalent region of
      two European isolates of HIV-1 (ACH320.3.1 and HIV-1Han-2). Neither of these
      viruses had been passaged in T cell lines for prolonged periods prior to
      molecular cloning. Virus stocks were prepared of both SHIV constructs. In vitro,
      the relative ability of each clone to replicate in four T cell lines mirrored
      closely the pattern observed with the parental virus donating the envelope
      sequences. In vivo, only one of the chimeric viruses was infectious in cynomolgus
      macaques and its recovery was transient. The factors that affect the replication
      of SHIVs in vitro and in vivo are discussed.

PMID- 9171225
TI  - Enhancement of humoral immunity to SIVenv following simultaneous inoculation of
      mice by three recombinant adenoviruses encoding SIVenv/poliovirus chimeras, Tat
      and Rev.
AB  - A means of inducing gene expression by simultaneous infection with three
      recombinant adenoviruses (Ad) is described. The simian immunodeficiency virus
      (SIV) envelope-coding region was placed under the control of the human
      immunodeficiency virus type 1 (HIV-1) Tat and Rev proteins provided in trans by
      distinct Ad vectors (Ad-tat; Ad-rev). Coinfection of cells with the three
      recombinant adenoviruses led to induction of high levels of SIV env mRNA and
      protein synthesis, while inoculation of mice elicited anti-Env antibodies.
      Insertion of the poliovirus VP1 neutralization epitope (C3) in the V1
      hypervariable region of SIV envelope not only proved to be highly immunogenic for
      the poliovirus epitope but also enhanced the kinetics of anti-SIV Env antibody
      production. By contrast, insertion in V4 elicited no anti-C3 response and only
      normal anti-Env responses.

PMID- 9171226
TI  - Sequence analysis of an HIV type 1 env subtype E isolate from Thailand with
      discordant V3-loop serotyping.

PMID- 9171227
TI  - The origin of the special issue.

PMID- 9171228
TI  - Molecular Endocrinology, the early years: recollections by the first Editor-in
      Chief.

PMID- 9171229
TI  - Coactivator and corepressor regulation of the agonist/antagonist activity of the
      mixed antiestrogen, 4-hydroxytamoxifen.
AB  - Mixed antiestrogens, such as 4-hydroxytamoxifen (4HT), act as either partial
      agonists or antagonists of estrogen receptor (ER) function in a tissue-, cell-,
      and promoter-specific manner, suggesting that intracellular factors modulate
      their ability to regulate transcription. To determine whether coactivators and
      corepressors have the capacity to modulate the relative agonist/antagonist
      activity of 4HT, ER-dependent gene expression was measured in the absence or
      presence of expression vectors for SRC-1 (steroid receptor coactivator-1) or SMRT
      (silencing mediator of retinoic acid and thyroid hormone receptors). In Hep G2
      cells in which 4HT is an agonist, exogenous SRC-1 enhanced estradiol (E2)- and
      4HT-stimulated transcription in a dose-dependent manner, while SMRT
      overexpression strongly reduced basal and 4HT-stimulated gene expression with no
      effect on E2 activity. These observations were not cell- or promoter-specific
      inasmuch as similar results were obtained in HeLa cells under conditions in which
      4HT is an antagonist. A protein-protein interaction assay indicated that the full
      length ER binds to SMRT in vitro. To assess whether relative coactivator and
      corepressor expression within a given cell could modulate the balance of 4HT
      agonist/antagonist activity, SRC-1 and SMRT were coexpressed. SMRT overexpression
      blocked SRC-1 coactivation of 4HT-stimulated gene expression and preferentially
      inhibited 4HT agonist activity whether or not exogenous SRC-1 was present. The
      cumulative data in this model system indicate that the relative expression of
      coactivators and corepressors can modulate 4HT regulation of ER transcriptional
      activity and suggest they could contribute to the tissue-specific ability of
      mixed antiestrogens to activate or inhibit ER-mediated gene expression.

PMID- 9171230
TI  - The role of interleukin-2 in combination adenovirus gene therapy for head and
      neck cancer.
AB  - Interleukin-2 (IL-2) gene therapy alone and in combination with the herpes
      thymidine kinase gene (tk) was used to evaluate immunological responses and
      antitumor effects in head and neck cancer. Established floor of mouth squamous
      cell carcinomas in C3H/HeJ mice were directly injected with recombinant
      adenoviral vectors carrying both therapeutic and control genes. One week after
      adenoviral gene transfer, only the animals treated with combination IL-2+tk or tk
      alone demonstrated significant tumor regression. Residual tumors were harvested
      for microscopic evaluation and immunohistochemistry staining, which revealed a
      predominance of CD8+ lymphocytes in the tumor beds of the animals treated with IL
      2. To evaluate the systemic immune effects of IL-2, animals treated with single
      or combination gene therapy received a second site challenge with parental tumor
      cells or a heterologous but syngeneic sarcoma cell line. Mice treated with
      combination IL-2 and tk demonstrated a protective systemic immunity specific to
      the parental tumor cell line, whereas no systemic immune response was evident in
      mice receiving IL-2 alone. In a separate experiment, a range of concentrations of
      the adenovirus IL-2 vector were used to treat established tumors. Even with the
      maximal single-dose adenovirus concentration, IL-2 alone was ineffective as a
      single therapy. These results support the use of adenovirus-mediated gene
      transfer of IL-2 as an effective immunotherapy when used adjuvantly with the tk
      "suicide gene".

PMID- 9171231
TI  - Role of estrogen receptor-alpha in the anterior pituitary gland.
AB  - Targeted insertional disruption of the mouse estrogen receptor-alpha (ER alpha)
      gene has provided a genetic model in which to test hypotheses that estrogens
      exert important effects in development and homeostatic functions of the anterior
      pituitary gland, particularly in the lactotroph and gonadotroph cell types.
      Analysis of ER alpha gene-disrupted mice reveals a marked reduction in PRL mRNA
      and a decrease in lactotroph cell number, but normal specification of lactotroph
      cell phenotype. Gonadotropin mRNA levels in ER alpha gene-disrupted female mice
      are elevated, consistent with previously described transcriptional suppression of
      gonadotropin subunit gene expression in response to sustained administration of
      estrogen in wild type mice. These results provide genetic evidence that ER alpha
      plays a critical role in PRL and gonadotropin gene transcription and is involved
      in lactotroph cell growth, but is not required for specification of lactotroph
      cell phenotype.

PMID- 9171232
TI  - Differential effects of nuclear receptor corepressor (N-CoR) expression levels on
      retinoic acid receptor-mediated repression support the existence of dynamically
      regulated corepressor complexes.
AB  - Thyroid hormone and retinoic acid receptors are members of the nuclear receptor
      superfamily of ligand-dependent transcription factors that stimulate the
      transcription of target genes in the presence of activating ligands and repress
      transcription in their absence. Transcriptional repression by the thyroid hormone
      and retinoic acid receptors has been proposed to be mediated by the nuclear
      receptor corepressor, N-CoR, or the related factor, SMRT (silencing mediator of
      retinoic acid and thyroid hormone receptors). Recent studies have suggested that
      transcriptional repression by N-CoR involves a corepressor complex that also
      contains mSin3A/B and the histone deacetylase, RPD3. In this manuscript, we
      demonstrate that transcriptional repression by the retinoic acid receptor can be
      either positively or negatively regulated by changes in the levels of N-CoR
      expression, suggesting a relatively strict stoichiometric relationship between N
      CoR and other components of the corepressor complex. Consistent with this
      interpretation, overexpression of several functionally defined domains of N-CoR
      also relieve repression by nuclear receptors. N-CoR is distributed throughout the
      nucleus in a nonuniform pattern, and a subpopulation becomes concentrated into
      several discrete dot structures when highly expressed. RPD3 is also widely
      distributed throughout the nucleus in a nonuniform pattern. Simultaneous imaging
      of RPD3 and N-CoR suggest that a subset of each of these proteins colocalize,
      consistent with the existence of coactivator complexes containing both proteins.
      In addition, a substantial fraction of both N-CoR and mSin3 A/B appear to be
      independently distributed. These observations suggest that interactions between
      RPD3 and Sin3/N-CoR complexes may be dynamically regulated.

PMID- 9171233
TI  - The partial agonist activity of antagonist-occupied steroid receptors is
      controlled by a novel hinge domain-binding coactivator L7/SPA and the
      corepressors N-CoR or SMRT.
AB  - Steroid receptor antagonists, such as the antiestrogen tamoxifen or the
      antiprogestin RU486, can have inappropriate agonist-like effects in tissues and
      tumors. To explain this paradox we postulated that coactivators are inadvertently
      brought to the promoters of DNA-bound, antagonist-occupied receptors. The human
      (h) progesterone receptor (PR) hinge-hormone binding domain (H-HBD) was used as
      bait in a two-hybrid screen of a HeLa cDNA library, in which the yeast cells were
      treated with RU486. We have isolated and characterized two interesting steroid
      receptor-interacting proteins that regulate transcription in opposite directions.
      The first is L7/SPA, a previously described 27-kDa protein containing a basic
      region leucine zipper domain, having no known nuclear function. When coexpressed
      with tamoxifen-occupied estrogen receptors (hER) or RU486-occupied hPR or
      glucocorticoid receptors (hGR), L7/SPA increases the partial agonist activity of
      the antagonists by 3- to 10-fold, but it has no effect on agonist-mediated
      transcription. The interaction of L7/SPA with hPR maps to the hinge region, and
      indeed, the hPR hinge region squelches L7/SPA-dependent induction of antagonist
      mediated transcription. Interestingly, pure antagonists that lack partial agonist
      effects, such as the antiestrogen ICI164,384 or the antiprogestin ZK98299, cannot
      be up-regulated by L7/SPA. We also isolated, cloned, and sequenced the human
      homolog (hN-CoR) of the 270-kDa mouse (m) thyroid/retinoic acid receptor
      corepressor. Binding of hN-CoR maps to the hPR-HBD. mN-CoR, and a related human
      corepressor, SMRT, suppress RU486 or tamoxifen-mediated partial agonist activity
      by more than 90%. This suppression is completely squelched by overexpression of
      the hPR H-HBD. Additionally, both corepressors reverse the antagonist-dependent
      transcriptional up-regulation produced by L7/SPA. Our data suggest that the
      direction of transcription by antagonist-occupied steroid receptors can be
      controlled by the ratio of coactivators to corepressors recruited to the
      transcription complex by promoter-bound receptors. In normal tissues and in
      hormone-resistant breast cancers in which the agonist activity of mixed
      antagonists predominates, steroid receptors may be preferentially bound by
      coactivators. This suggests a strategy by which such partial agonist activity can
      be eliminated and by which candidate receptor ligands can be screened for this
      activity.

PMID- 9171234
TI  - An X-linked NDI mutation reveals a requirement for cell surface V2R expression.
AB  - Function and biochemical properties of the V2 vasopressin receptor (V2R) mutant
      R337ter, identified in patients suffering from X-linked recessive nephrogenic
      diabetes insipidus, were investigated by expression in COS.M6 or HEK293 cells.
      Binding assays and measurements of adenylyl cyclase activity failed to detect
      function for the truncated receptor, although metabolic labeling demonstrated
      normal levels of protein synthesis. ELISA assays performed on cells expressing
      the receptors tagged at the amino terminus with the HA epitope failed to detect
      V2R R337ter on the plasma membrane. Treatment with endoglycosidase H revealed
      that the receptor was present only as a precursor form because the mature R337ter
      V2R, resistant to endoglycosidase H treatment, was not detected. The precursor of
      V2R-R337ter had a longer half-life than that of the wild type V2R, suggesting
      that arrested maturation may slow the degradation of the precursor. Unrelated
      experiments had demonstrated that V2R-G345ter, containing eight additional amino
      acids, was expressed on the plasma membrane and functioned normally. Receptor
      truncations longer than 337ter revealed that four of the eight amino acids
      identified initially provided the minimum length required for the protein to
      acquire cell surface expression. This was shown by the production of mature
      receptor (V2R-341ter) detectable in SDS-PAGE, which mediated arginine vasopressin
      stimulation of adenylyl cyclase activity and bound ligand. In addition, the
      identity of amino acid 340 was found to play a role in this phenomenon. In
      conclusion, these data demonstrate that the V2R R337ter is nonfunctional because
      it does not reach the plasma membrane and that the minimal protein length
      required for translocation of the V2R to the cell surface is sufficient to confer
      function to the receptor protein. They also suggest the existence of a protein
      quality control in the endoplasmic reticulum independent of glycosylation.

PMID- 9171235
TI  - Gene silencing by chicken ovalbumin upstream promoter-transcription factor I
      (COUP-TFI) is mediated by transcriptional corepressors, nuclear receptor
      corepressor (N-CoR) and silencing mediator for retinoic acid receptor and thyroid
      hormone receptor (SMRT).
AB  - Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) are orphan
      receptors that belong to the steroid/thyroid hormone receptor (TR) superfamily
      and can repress the transcriptional activity of several target genes; however,
      the precise mechanism of this repression is unknown. Transfection of a Gal4 DNA
      binding domain fused to the putative ligand-binding domain of COUP-TFI (Gal4-COUP
      TFI) significantly represses the basal transcriptional activity of a reporter
      gene containing Gal4-binding sites. Cotransfection of COUP-TFI can relieve the
      Gal4-COUP-TFI repression in a dose-dependent manner. In contrast, COUP-TFI
      delta35, which lacks the repressor domain (the C-terminal 35 amino acids), fails
      to relieve this repression. This finding suggests that the repressor domain of
      COUP-TFI may squelch a limiting amount of corepressor in HeLa cells. In addition,
      increasing concentrations of TRbeta also can relieve the COUP-TFI repression in a
      hormone-sensitive manner. Similarly, overexpression of increasing concentration
      of COUP-TFI, but not COUP-TFI delta35, can squelch the silencing activity of the
      unliganded TRbeta. Collectively, these results indicate that COUP-TFI and TRbeta
      share a common corepressor(s) for their silencing activity. To determine which
      corepressor is involved in the COUP-TF-silencing activity, we used a yeast two
      hybrid and in vitro GST pull-down assays to demonstrate that COUP-TFI can
      interact with the fragment of N-CoR (nuclear receptor-corepressor) encoding amino
      acids 921-2453 and the fragments of SMRT (silencing mediator for retinoic acid
      receptor and TR) encoding amino acids 29-564 and 565-1289, respectively.
      Interestingly, the fragment of SMRT encoding amino acids 1192-1495, which
      strongly interacts with TRbeta, interacts very weakly with COUP-TFI. Furthermore,
      overexpression of N-CoR or SMRT potentiates the silencing activity of COUP-TFI
      and can relieve the COUP-TFI-mediated squelching of Gal4-COUP-TFI activity.
      Therefore, our studies indicate that N-CoR and SMRT act as corepressors for the
      COUP-TFI silencing activity.

PMID- 9171236
TI  - Defective survival and activation of thymocytes in transgenic mice expressing a
      catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV.
AB  - We have generated transgenic mice that express a catalytically inactive form of
      Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) specifically in thymic T
      cells. The presence of this protein results in a markedly reduced thymic
      cellularity, although the distribution of the remaining cells is normal based on
      evaluation of the CD4 and CD8 cell surface antigens that are used to gauge T cell
      development. Isolated thymic T cells from the transgenic mice also show a
      dramatically decreased survival rate when evaluated in culture under conditions
      that do not favor activation. When challenged with an activating stimulus such as
      alpha-CD3 or a combination of phorbol ester plus ionophore, the cells are
      severely compromised in their ability to produce the cytokine interleukin-2 (IL
      2). Reduction of IL-2 production is secondary to the inability to phosphorylate
      the cAMP response element binding protein, CREB, and induce expression of the
      immediate early genes such as Fos B that are required to transactivate the IL-2
      promoter. Because transgene expression was regulated by the proximal promoter of
      the murine lck gene and this promoter is inactivated in T cells that exit the
      thymus, the mutant hCaMKIV is not present in peripheral T cells. Consequently, T
      lymphocytes present in the spleen can be activated normally in response to either
      stimulus mentioned above, demonstrating that the effects of the inactive CaMKIV
      on activation are reversible. Our results suggest that CaMKIV may represent a
      physiologically relevant CREB kinase in T cells and that the enzyme is also
      required to ensure normal expansion of T cells in the thymus. Whereas the pathway
      responsible for this latter role is yet to be elucidated, it is unlikely to
      include CREB phosphorylation.

PMID- 9171237
TI  - Regulation of G(q/11)alpha by the gonadotropin-releasing hormone receptor.
AB  - Evidence from use of pertussis and cholera toxins and from NaF suggested the
      involvement of G proteins in GnRH regulation of gonadotrope function. We have
      used three different methods to assess GnRH receptor regulation of G(q/11)alpha
      subunits (G(q/11)alpha). First, we used GnRH-stimulated palmitoylation of
      G(q/11)alpha to identify their involvement in GnRH receptor-mediated signal
      transduction. Dispersed rat pituitary cell cultures were labeled with [9,10
      (3)H(N)]-palmitic acid and immunoprecipitated with rabbit polyclonal antiserum
      made against the C-terminal sequence of G(q/11)alpha. The immunoprecipitates were
      resolved by 10% SDS-PAGE and quantified. Treatment with GnRH resulted in time
      dependent (0-120 min) labeling of G(q/11)alpha. GnRH (10(-12), 10(-10), 10(-8),
      or 10(-6) g/ml) for 40 min resulted in dose-dependent labeling of G(q/11)alpha
      compared with controls. Cholera toxin (5 microg/ml; activator of G(i)alpha),
      pertussis toxin (100 ng/ml; inhibitor of G(i)alpha actions) and Antide (50 nM;
      GnRH antagonist) did not stimulate palmitoylation of G(q/11)alpha above basal
      levels. However, phorbol myristic acid (100 ng/ml; protein kinase C activator)
      stimulated the palmitoylation of G(q/11)alpha above basal levels, but not to the
      same extent as 10(-6) g/ml GnRH. Second, we used the ability of the third
      intracellular loop (3i) of other seven-transmembrane segment receptors that
      couple to specific G proteins to antagonize GnRH receptor-stimulated signal
      transduction and therefore act as an intracellular inhibitor. Because the third
      intracellular loop of alpha1B-adrenergic receptor (alpha1B 3i) couples to
      G(q/11)alpha, it can inhibit G(q/11)alpha-mediated stimulation of inositol
      phosphate (IP) turnover by interfering with receptor coupling to G(q/11)alpha.
      Transfection (efficiency 5-7%) with alpha1B 3i cDNA, but not the third
      intracellular loop of M1-acetylcholine receptor (which also couples to
      G(q/11)alpha), resulted in 10-12% inhibition of maximal GnRH-evoked IP turnover,
      as compared with vector-transfected GnRH-stimulated IP turnover. The third
      intracellular loop of alpha2A adrenergic receptor, M2-acetylcholine receptor
      (both couple to G(i)alpha), and D1A-receptor (couples to G(s)alpha) did not
      inhibit IP turnover significantly compared with control values. GnRH-stimulated
      LH release was not affected by the expression of these peptides. Third, we
      assessed GnRH receptor regulation of G(q/11)alpha in a PRL-secreting adenoma cell
      line (GGH(3)1') expressing the GnRH receptor. Stimulation of GGH(3)1' cells with
      0.1 microg/ml Buserelin (a metabolically stable GnRH agonist) resulted in a 15
      20% decrease in total G(q/11)alpha at 24 h following agonist treatment compared
      with control levels; this action of the agonist was blocked by GnRH antagonist,
      Antide (10(-6) g/ml). Neither Antide (10(-6) g/ml, 24 h) alone nor phorbol
      myristic acid (0.33-100 ng/ml, 24 h) mimicked the action of GnRH agonist on the
      loss of G(q/11)alpha immunoreactivity. The loss of G(q/11)alpha immunoreactivity
      was not due to an effect of Buserelin on cell-doubling times. These studies
      provide the first direct evidence for regulation of G(q/11)alpha by the GnRH
      receptor in primary pituitary cultures and in GGH3 cells.

PMID- 9171238
TI  - Identification of a third autonomous activation domain within the human estrogen
      receptor.
AB  - Using a genetic selection system established in the yeast Saccharomyces
      cerevisiae, we have isolated, by random mutagenesis of the human estrogen
      receptor (ER), six mutants that display constitutive transcriptional activity.
      All of the mutants identified contained single base insertions or deletions
      leading to frameshift mutations, resulting in receptor truncations within the
      hormone-binding domain between amino acids (aa) 324-351. Interestingly, an ER
      mutant (aa 1-282) was transcriptionally inactive in yeast, suggesting that a
      domain important for transcriptional activity lies between aa 282 and 351 within
      human ER. Deletions representative of the mutants isolated in the yeast system
      were created in mammalian expression vectors and examined for transcriptional
      activity in animal cells to determine the physiological relevance of this domain.
      Receptors truncated at aa 282 were either weakly active or inactive; however, an
      ER deletion at aa 351 was approximately 50% as active as wild type ER (induced
      with estrogen). Furthermore, a chimeric receptor consisting of the DNA binding
      domain of GAL4 fused to aa 282-351 of the human ER was transcriptionally active
      on a GAL4 reporter. We conclude, therefore, that an autonomous activation domain
      (referred to as AF2a), functional in both yeast and mammalian cells, lies between
      aa 282-351 of the human ER.

PMID- 9171239
TI  - Analysis of the functional role of steroid receptor coactivator-1 in ligand
      induced transactivation by thyroid hormone receptor.
AB  - The nuclear hormone receptors belonging to the steroid/thyroid/retinoid receptor
      superfamily are ligand-inducible transcription factors. These receptors modulate
      transcription of specific cellular genes, either positively or negatively, by
      interacting with specific hormone response elements located near the target
      promoters. Recent studies indicated that the hormone- occupied, DNA-bound
      receptor acts in concert with a cellular coregulatory factor, termed coactivator,
      and the basal transcription machinery to mediate gene activation. Consistent with
      this scenario, a number of nuclear proteins with potential coactivator function
      have been isolated. In the present study, we demonstrate that steroid receptor
      coactivator-1 (SRC-1), a recently isolated candidate coactivator, functions as a
      positive regulator of the thyroid hormone receptor (TR)-mediated transactivation
      pathway. In transient transfection experiments, coexpression of SRC-1
      significantly enhanced ligand-dependent transactivation of a thyroid hormone
      response element (TRE)-linked promoter by human TRbeta. Our studies revealed that
      deletion of six amino acids (451-456) in the extreme COOH-terminal region of
      TRbeta resulted in a receptor that retained the ability to bind T3 but failed to
      be stimulated by SRC-1. These six amino acids are part of an amphipathic helix
      that is highly conserved among nuclear hormone receptors and contains the core
      domain of the ligand-dependent transactivation function, AF-2. In agreement with
      this observation, in vitro protein binding studies showed that SRC-1 interacted
      with a ligand binding domain peptide (145-456) of TRbeta in a T3-dependent
      manner, whereas it failed to interact with a mutant ligand binding domain lacking
      the amino acids (451-456). We demonstrated that a synthetic peptide containing
      the COOH-terminal amino acids (437-456) of TRbeta efficiently blocked the ligand
      induced binding of SRC-1 to the receptor. These results suggest that the
      conserved amphipathic helix that constitutes the AF-2 core domain of TRbeta is
      critical for interaction with SRC-1 and thereby plays a central role in
      coactivator-mediated transactivation. We further observed that a heterodimer of
      TRbeta and retinoid X receptor-alpha (RXR alpha), either in solution or bound to
      a DR+4 TRE, recruited SRC-1 in a T3-dependent manner. The AF-2 of TR was clearly
      involved in this process because a TR-RXR heterodimer containing a mutant TRbeta
      (1-450) with impaired AF-2 failed to bind to SRC-1. Surprisingly, the RXR
      specific ligand 9-cis-retinoic acid induced binding of SRC-1 to the RXR component
      of the TRE-bound heterodimer. This novel finding suggests that RXR, as a
      heterodimeric partner of TR, has the potential to play an active role in
      transcriptional regulation. Our results raise the interesting possibility that a
      RXR-specific ligand may modulate T3-mediated signaling by inducing additional
      interactions between TRE-bound TR-RXR heterodimer and the coactivator.

PMID- 9171240
TI  - Activation of transcription by progesterone receptor involves derepression of
      activation functions by a cofactor.
AB  - Hormone-induced progesterone receptors (PR) bound to response elements stimulate
      transcription initiation at target promoters through a mechanism that presumably
      involves cofactors or coactivators. To allow identification of such cofactors of
      transcriptional activation in a functional assay, we have established a
      reconstituted transcription system that is characterized by a specific loss of
      responsiveness to purified baculovirus-expressed wild type PR. In contrast to
      wild type PR, a C-terminally truncated PR mutant displayed strong activation
      potential in this system. As the purified recombinant full-length PR is capable
      of DNA binding, our results suggest that C-terminal sequences of PR mediate a cis
      repression of N-terminal activation functions. Moreover, using this PR
      nonresponsive transcription system, we identified and partially purified an
      activity from rat liver, termed COPRA (cofactor of PR activation), that restores
      transactivation by full-length PR. Characterization of COPRA revealed that this
      cofactor exhibits activator specificity and is not involved in basal
      transcription. We postulate that COPRA acts by relieving the repression of
      activation functions mediated by C-terminal sequences.

PMID- 9171241
TI  - Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of
      peroxisome proliferator-activated receptors by coactivator-dependent receptor
      ligand assay.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors
      controlling the expression of genes involved in lipid homeostasis. PPARs activate
      gene transcription in response to a variety of compounds including hypolipidemic
      drugs as well as natural fatty acids. From the plethora of PPAR activators,
      Scatchard analysis of receptor-ligand interactions has thus far identified only
      four ligands. These are the chemotactic agent leukotriene B4 and the
      hypolipidemic drug Wy 14,643 for the alpha-subtype and a prostaglandin J2
      metabolite and synthetic antidiabetic thiazolidinediones for the gamma-subtype.
      Based on the hypothesis that ligand binding to PPAR would induce interactions of
      the receptor with transcriptional coactivators, we have developed a novel ligand
      sensor assay, termed coactivator-dependent receptor ligand assay (CARLA). With
      CARLA we have screened several natural and synthetic candidate ligands and have
      identified naturally occurring fatty acids and metabolites as well as
      hypolipidemic drugs as bona fide ligands of the three PPAR subtypes from Xenopus
      laevis. Our results suggest that PPARs, by their ability to interact with a
      number of structurally diverse compounds, have acquired unique ligand-binding
      properties among the superfamily of nuclear receptors that are compatible with
      their biological activity.

PMID- 9171242
TI  - Inhibition of retinoid signaling in transgenic mice alters lipid processing and
      disrupts epidermal barrier function.
AB  - To explore the role of retinoids in epidermal development, we recently targeted
      expression of a dominant-negative, retinoic acid receptor mutant (RAR alpha403)
      in the epidermis of transgenic mice and observed an unexpected loss of barrier
      function. In this paper, we demonstrate that transgenic mice expressing the RAR
      alpha403 transgene show attenuated responsiveness to topical application of all
      trans retinoic acid, in agreement with our previous in vitro data. We also show
      that the vitamin D3 receptor is unaffected in its ability to transactivate in the
      presence of the dominant-negative RAR alpha403 transgene, indicating that the RAR
      alpha403 is unlikely to be functioning through a global sequestration of retinoid
      X receptors. Additionally, we show that the disruption of epidermal barrier
      function results in a dramatic 4 C drop in mean body surface temperature,
      probably accounting for the extremely high incidence of neonatal mortality in
      severely phenotypic pups. Some severely affected pups do survive and show a
      pronounced hyperkeratosis at postpartum day 4, consistent with previously
      documented effects of vitamin A deficiency. Biochemical analysis of the severely
      phenotypic neonates indicates elevated phospholipids and glycosylceramides in the
      stratum comeum, which results from altered lipid processing. Taken together with
      previous studies, these data provide strong evidence linking the retinoid
      signaling pathway with modulation of lipid processing required for formation of
      epidermal barrier function.

PMID- 9171243
TI  - Mammary gland development is mediated by both stromal and epithelial progesterone
      receptors.
AB  - A combination of a knockout mouse model, tissue transplantation, and gene
      expression analysis has been used to investigate the role of steroid hormones in
      mammary gland development. Mouse mammary gland development was examined in
      progesterone receptor knockout (PRKO) mice using reciprocal transplantation
      experiments to investigate the effects of the stromal and epithelial PRs on
      ductal and lobuloalveolar development. The absence of PR in transplanted donor
      epithelium, but not in recipient stroma, prevented normal lobuloalveolar
      development in response to estrogen (E) and progesterone (P) treatment.
      Conversely, the presence of PR in the transplanted donor epithelium, but not in
      the recipient stroma, revealed that PR in the stroma may be necessary for ductal
      development. Members of the Wnt growth factor family, Wnt-2 and Wnt-5B, were
      employed as molecular markers of steroid hormone action in the mammary gland
      stroma and epithelium, respectively, to investigate the systemic effects of E and
      P. Hormonal treatment of intact, ovariectomized, and PR-/- mice and mice after
      transplantation of PR-/- epithelium into wild type (PR+/+) stroma demonstrated
      that these two locally acting growth factors are regulated by independent
      mechanisms. Wnt-2 is acutely repressed by E alone, while Wnt-5B gene expression
      is induced only after chronic treatment with both E and P. Wnt 5B appears to be
      one of the few molecular markers of P action in the mammary epithelium. This
      study suggests that the regulation of mammary gland development by steroid
      hormones is mediated by distinct effects of the stromal and epithelial PR and
      differential growth factor expression.

PMID- 9171244
TI  - Competition between negative acting YY1 versus positive acting serum response
      factor and tinman homologue Nkx-2.5 regulates cardiac alpha-actin promoter
      activity.
AB  - Transcription of sarcomeric alpha-actin genes is developmentally regulated during
      skeletal and cardiac muscle development through fine-tuned control mechanisms
      involving multiple cooperative and antagonistic transcription factors. Among the
      cis-acting DNA elements recognized by these factors is the sequence CC(A/T)6GG of
      the serum response element (SRE), which is present in a number of growth factor
      inducible and myogenic specified genes. We recently showed that the cardiogenic
      homeodomain factor, Nkx-2.5, served as a positive acting accessory factor for
      serum response factor (SRF) and together provided strong transcriptional
      activation of the cardiac alpha-actin promoter. In addition, Nkx-2.5 and SRF
      collaborated to activate the endogenous murine cardiac alpha-actin gene in 10T1/2
      fibroblasts, by a mechanism that involved coassociation of SRF and Nkx-2.5 on
      intact SREs of the alpha-actin promoter. Here, we show that the second SRE of the
      avian cardiac alpha-actin promoter served as a binding site for Nkx-2.5, SRF, and
      zinc finger containing GLI-Kruppel-like factor, YY1. Expression of YY1 inhibited
      cardiac alpha-actin promoter activity, whereas coexpression of Nkx-2.5 and SRF
      was able to partially reverse YY1 repression. Displacement of YY1 binding by Nkx
      2.5/SRF complex occurs through mutually exclusive binding across the CaSRE2. The
      interplay and functional antagonism between YY1 and Nkx-2.5/SRF might constitute
      a developmental as well as a physiologically regulated mechanism that modulates
      cardiac alpha-actin gene expression during cardiogenesis.

PMID- 9171245
TI  - Phosphorylation of human progesterone receptor by cyclin-dependent kinase 2 on
      three sites that are authentic basal phosphorylation sites in vivo.
AB  - The human progesterone receptor (hPR) in T47D breast cancer cells is
      phosphorylated on at least nine different serine residues. We have previously
      reported the identification of five sites; three are hormone inducible (Ser102,
      Ser294 and Ser345), and their phosphorylation correlates with the timing of the
      change in receptor mobility on gel electrophoresis in response to hormone
      treatment. The other two sites, Ser81 and Ser162, along with the remaining sites,
      are basally phosphorylated and exhibit a general increase in phosphorylation in
      response to hormone. With the exception of Ser81, all of these sites are in Ser
      Pro motifs, suggesting that proline-directed kinases are responsible for their
      phosphorylation. We now report that cyclin A-cyclin-dependent kinase-2 complexes
      phosphorylate hPR-B in vitro with a high stoichiometry on three sites that are
      authentic basal sites in vivo. One of these is Ser162, which has been described
      previously. The other two sites are identified here as Ser190 and Ser400. The
      specificity and stoichiometry of the in vitro phosphorylation suggest that hPR
      phosphorylation may be regulated in a cell cycle-dependent manner in vivo.

PMID- 9171247
TI  - Nerve biopsy.

PMID- 9171246
TI  - Hepatic insulin gene expression as treatment for type 1 diabetes mellitus in
      rats.
AB  - Type 1 diabetes mellitus is caused by a lack of insulin that results from the
      autoimmune destruction of the pancreatic beta-cells. Severe diabetes, if not
      controlled by periodic insulin injections, can lead to ketoacidosis and death. We
      have previously shown that sustained low level production of insulin in the liver
      of diabetic rats prevented their death from complications of diabetes. To test
      the hypothesis that there is a window of serum insulin concentrations that can
      prevent ketoacidosis without significant risk of hypoglycemia secondary to
      hyperinsulinemia, rats were infused with various doses of a recombinant
      retrovirus encoding an engineered rat preproinsulin-1 gene. The gene was
      engineered to allow processing into mature insulin by the protease furin. At the
      lower doses tested, fatal ketoacidosis was prevented, but the rats exhibited
      nonfasting hyperglycemia. At intermediate doses, which resulted in serum insulin
      concentrations of 1.6 mg/ml, the rats achieved near-normoglycemia and no serum
      ketones. These rats did not exhibit hypoglycemia even during a 24-h fast. At high
      virus doses, the animals achieved nonfasting normoglycemia but exhibited
      hypoglycemia during the fast. In conclusion, we have defined a therapeutic window
      of hepatic insulin expression that provides protection against ketoacidosis
      without significant risk of hypoglycemia. This window of sustained hepatic
      insulin expression might permit its development into a novel treatment modality
      for the prevention of ketoacidosis in patients with severe insulin-dependent
      diabetes mellitus.

PMID- 9171248
TI  - Twin studies in diabetes mellitus.
AB  - Twin studies are a valuable way of determining the relative significance of
      genetic and environmental factors in the aetiology of disease. In diabetes
      mellitus, they are of importance, since the aetiologies of Type 1 (insulin
      dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are probably
      different. However the results of twin studies have not always been reliable.
      Strict adherence to methodological guidelines is necessary to ensure the validity
      of the results that are obtained. These guidelines relate to ascertainment of a
      twin sample, confirmation of zygosity, and effects of sampling. Critical review
      of twin studies in diabetes performed to date imply provisionally a very strong
      genetic input to the aetiology of Type 1 diabetes. In Type 2 diabetes genetic and
      environmental factors are probably of equal importance.

PMID- 9171249
TI  - Persistent postoperative complaints after whole sural nerve biopsies in diabetic
      and non-diabetic subjects.
AB  - The postoperative effects of a whole sural nerve biopsy in diabetic (11) and non
      diabetic (10 healthy controls, 10 patients with impaired glucose tolerance and 2
      patients with polyneuropathy) subjects were investigated by a mailed
      questionnaire 20-44 months after the surgical procedure (10/11 vs 21/22 answers
      received). Pain in the biopsy area at follow-up was reported in 4/10 of the
      diabetic patients (p = 0.01) but in none of the non-diabetic subjects (0/21). An
      increased number (p = 0.01) of diabetic patients (5/10 vs 1/21) had cold
      intolerance in their foot or leg whereas 11/31 of all patients had dysaesthesia
      in the affected skin. Overall 6/31 patients described serious problems at the
      time of the questionnaire, and 4 of this 6 having diabetes. Loss of sensation was
      reported in almost all subjects irrespective of diabetes or not; however, a
      decrease in the area of loss of sensation was reported most often in diabetic
      patients (8/10 vs 8/21, p = 0.02). It is concluded that whole surval nerve
      biopsies give rise to persistent problems both in diabetic and non-diabetic
      subjects. The reason for a sural nerve biopsy has always to be carefully
      considered before being conducted.

PMID- 9171250
TI  - The natural history of acute Charcot's arthropathy in a diabetic foot specialty
      clinic.
AB  - The aim of this longitudinal study was to report on the clinical characteristics
      and treatment course of acute Charcot's arthropathy at a tertiary care diabetic
      foot clinic. Fifty-five diabetic subjects, with a mean age of 58.6 +/- 8.5 years,
      were studied. All patients were treated with serial total contact casting until
      quiescence. Following casting and before transfer to prescription footwear,
      patients were eased into unprotected weightbearing via a removable cast walker.
      This cohort was followed for their entire treatment course and for a mean 92.6 +/
      33.7 weeks following return to shoes. Pain was the most frequent presenting
      complaint in these otherwise insensate patients (76%). The mean duration of
      casting was 18.5 +/- 10.6 weeks. Patients returned to footwear in a mean 28.3 +/-
      14.5 weeks. Nine per cent of the population had bilateral arthropathy. These
      subjects were casted significantly longer than the unilateral group (p < 0.02).
      Surgery was performed on 25 % of patients, with approximately two-thirds of these
      procedures involving plantar exostectomies and one-third fusions of affected
      joints. Patients receiving surgery remained casted significantly longer than non
      surgical patients (p < 0.05). Additionally, men were casted longer than women (p
      < 0.008). Acute Charcot's arthropathy requires prompt, uncompromising reduction
      in weightbearing stress. Our data show that the ambulatory total contact cast is
      very effective for this. Regardless of the specific treatment method instituted,
      it is imperative that appropriate and aggressive treatment be undertaken
      immediately following diagnosis to help prevent progression to a profoundly
      debilitating, limb-threatening deformity.

PMID- 9171251
TI  - Signal-averaged electrocardiogram in patients with insulin-dependent (type 1)
      diabetes mellitus with and without diabetic neuropathy.
AB  - The purpose of this study was to investigate the presence of ventricular late
      potentials derived from signal-averaged ECG in patients with IDDM with and
      without diabetic neuropathy. Eighty patients with IDDM but without evidence of
      cardiac disease and 80 age-matched healthy control subjects were investigated.
      The corrected QT interval was measured from the standard surface
      electrocardiogram. Ventricular late potentials were derived from signal-averaged
      electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic
      neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of
      neuropathy. The corrected QT interval was significantly prolonged in patients
      with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x
      5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no
      significant prolongation of the corrected QT interval. Ventricular late
      potentials were present in 3 diabetic patients with an isolated peripheral
      neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic
      neuropathy had ventricular late potentials. Our data did not indicate an
      increased incidence of ventricular late potentials derived from signal-averaged
      electrocardiogram in diabetic patients independent of a coexisting diabetic
      neuropathy or a prolonged corrected QT interval.

PMID- 9171252
TI  - An assessment of blood pressure measurement in a diabetic clinic using random
      zero, semi-automated, and 24-hour monitoring.
AB  - We have undertaken a randomized, observer-blinded comparison of three different
      methods of assessing blood pressure in 40 outpatients with hypertension
      complicating diabetes mellitus: the Hawksley random zero sphygmomanometer (RZS)
      by two observers using a dual headed stethoscope; the semi-automated Dinamap
      monitor, and 24-h ambulatory blood pressure monitoring (ABPM) using a Spacelabs
      90207. The techniques were compared by plotting the difference against average of
      readings obtained by combinations of two techniques (RZS observer 1 vs 2; RZS
      (mean observer 1 and 2) vs Dinamap; RZS (mean observer 1 and 2) vs daytime ABPM;
      and Dinamap vs daytime ABPM). There was good agreement of readings with RZS,
      observers 1 and 2 and RZS with Dinamap and daytime ABPM. When the three methods
      were used to classify blood pressure control according to BDA criteria, it was
      found that they produced equivalent results and although mean systolic pressures
      appeared lower with ABPM this did not reach statistical significance. Overall
      control of systolic blood pressure was classified as unsatisfactory in 82% of
      patients, diastolic blood pressure was unsatisfactory in 55%. Fifty-five percent
      were determined to be nocturnal 'non-dippers' by ABPM. They were older: median
      age 62.9 (range 35.9-83.5) years compared to 48.2 (32.4-70.0) years for 'dippers'
      (p<0.05). Thirteen of the 18 patients who did dip overnight had creatinines
      within the normal laboratory range, whereas only 6 of 22 'non-dippers' had normal
      creatinines (median 91 (56-768) micromol l(-1) for 'dippers' vs 166 (76-479)
      micromol l(-1) for 'non-dippers', p < 0.001). Nineteen of the 29 males studied
      were 'non-dippers' compared with only 4 out of 11 females (p < 0.001). There was
      no association between dipper status, duration or type of diabetes or presence of
      proteinuria.

PMID- 9171253
TI  - Relationships between plasma leptin and insulin concentrations, but not insulin
      resistance, in non-insulin-dependent (type 2) diabetes mellitus.
AB  - In non-diabetic subjects, insulin concentrations and insulin resistance are
      clearly connected, and both correlate with leptin levels, making interpretations
      about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus
      (NIDDM), however, insulin concentrations and insulin resistance are less closely
      associated. Therefore, we examined the relationship of plasma leptin
      concentrations within insulin resistance and insulin levels in 32 subjects with
      NIDDM, who underwent measurement of insulin resistance with an insulin
      sensitivity test. Plasma leptin was measured with an in-house monoclonal
      immunoradiometric assay. Fasting leptin level correlated with BMI (r = 0.78; p <
      0.001), metabolic clearance rate of glucose (= -0.44; p = 0.015), and fasting
      specific insulin (r = 0.58; p = 0.001), but not with age, cholesterol,
      triglycerides or blood pressure (r = -0.26 to 0.21; p = NS). In linear regression
      analysis, after adjustment for BMI and gender, leptin concentrations correlated
      with those of insulin (partial r = 0.42; p = 0.025), but not insulin resistance
      (partial r = -0.10; p = NS). We conclude that in NIDDM, concentrations of plasma
      leptin are closely related to those of insulin per se and to obesity, but not to
      insulin resistance. Insulin may be an important regulator of leptin concentration
      in NIDDM.

PMID- 9171254
TI  - Admission plasma glucose and diabetes mellitus in elderly admissions to hospital.
AB  - Over 6 months, all admissions to three geriatric wards were studied to define an
      admission plasma glucose level (APG) that identified previously undiagnosed
      diabetes mellitus. Subjects with APG> or =7.0 mmol l(-1) had a modified oral
      glucose tolerance test (OGTT) when well before discharge if their dose of steroid
      and/or thiazide was constant, and they were neither terminally ill nor dead;
      excluded were 1 subject on reducing steroid doses, and 9 moribund admissions
      without APG. If the first 2 h OGTT result was > or =11.1 mmol l(-1), a second
      OGTT was performed 6 weeks later to fulfil 1985 WHO criteria. Subjects with
      APG<7.0 mmol l(-1) did not have OGTT. Seventy had a previous diagnosis of
      diabetes; scrutiny of records and OGTT refuted the diagnosis in 5, who were
      excluded from further analysis. Diabetes was only commonly found among those with
      APG> or =8.0 mmol l(-1), and the proportion was small until APG> or =13 mmol l(
      1), although even then only 47% (95% CI 21-73%) had diabetes. Fourteen of 28
      subjects with initial OGTT results suggesting diabetes were not diabetic on
      retesting. Inpatient mortality was higher if APG> or =7.0 (Odds ratio 2.82; CI
      1.63-4.89) or the subject had known diabetes (Odds ratio 2.43; CI 1.15-4.97)
      compared to APG<7; there was no age or sex difference between these three groups.
      We conclude that, unless overtly diabetic, diagnosis of diabetes in elderly
      medical admissions needs later confirmation.

PMID- 9171255
TI  - Prevalence of primary hyperparathyroidism in patients with diabetes mellitus.
AB  - The prevalence of previous or current primary hyperparathyroidism in 704 patients
      (390 male) with proven diabetes mellitus was 0.99% (7 patients, all female). One
      patient was known to have both disorders when the study commenced and 6 were
      discovered from the past history or by screening for hypercalcaemia. Diabetes was
      diagnosed at age 12 years or later, hyperparathyroidism from 45 years. Two
      patients were insulin-dependent. Diabetes preceded hyperparathyroidism in 3
      patients, followed it in 2, and occurred during the same year in 2. The
      prevalence is significantly greater (p < 0.02 to <0.001) than that of
      hyperparathyroidism in general populations (0.10-0.36%). When adjusted for the
      age and sex distribution of the population of the Halton Health District the
      expected prevalence of 0.82% remains significantly greater, except for the
      general population with 0.36% prevalence (0.1 > p > 0.05). This increased three-
      to fourfold prevalence of hyperparathyroidism in diabetes arises mainly from
      females, in whom the prevalences at age 15 years or over and at age 45 years or
      over are 2.23% and 2.54%, respectively.

PMID- 9171256
TI  - A case-control study of environmental factors associated with diabetes in the
      under 5s.
AB  - In 1992 a national case-control study was conducted through the British
      Paediatric Association Surveillance Unit (BPASU) framework to evaluate both the
      incidence of IDDM in children under 5 in that year and the effects of various
      putative trigger factors in the disease pathogenesis. A total of 218 sets of
      matched case-control questionnaire data established that paternal IDDM (odds
      ratio (OR) = 16.11, 95% confidence interval (CI) 1.94-133.7, p < = 0.001) is
      independently associated with increased risk, and higher birth order (OR = 0.64,
      CI 0.44-0.94, p = 0.021) and paternal age greater than 25 years (age 25-39 OR =
      0.52, CI 0.30-0.89; age 40 + OR = 0.23, CI 0.08-0.67, p = 0.009) with decreased
      risk of diabetes. Other factors previously implicated in the disease pathogenesis
      (birthweight, parental socio-economic status, infant feeding, and immunization
      record) showed no significant independent association with disease development.

PMID- 9171257
TI  - Confirmation of high incidence of type 1 (insulin-dependent) diabetes mellitus in
      Moroccan children in The Netherlands.
AB  - The incidence of Type 1 (insulin-dependent) diabetes mellitus among Moroccan
      children aged (0-19 years) in The Netherlands was determined. Point of reference
      was the data derived from the second nationwide incidence study on Type 1
      diabetes among children under 20 years of age. In that study the incidence among
      Dutch children was 13.2 100000(-1) year(-1). To scrutinize the data and to obtain
      more information a questionnaire was sent in 1993 to all specialists who had
      reported that they had diagnosed a patient with Type 1 diabetes during the years
      1988-1990 whose parents originated from Morocco, Turkey or other foreign
      countries. The questionnaire requested information on origin and migration of
      child and parents. The response to the questionnaire was 86% for the Moroccan
      children, 75% for the Turkish children and 100% for the children from other
      countries. In only one case a wrong country had been recorded. None of the
      patients had been in The Netherlands for less than 6 months before the diagnosis.
      The incidence for Moroccan children was 20.0 (95% CI 14.6-26.9) and for Turkish
      children 4.5 (95% CI 2.2-8.0) 100,000(-1) year(-1). It is concluded that the
      incidence of Type 1 diabetes in Moroccan children (0-19 years) is 1.5 times
      higher than in Dutch children and 4.5 times higher than in Turkish children.

PMID- 9171258
TI  - Possibilities and advantages with home sampling of HbA1c: eight years experience.
AB  - HbA1c is an accepted blood glucose index used for evaluating metabolic control in
      diabetes mellitus. HbA1c sampling at home makes it easier to continually keep
      track of the metabolic control for both the diabetic patient and the physician.
      Sampling and sample handling is at the same time simplified for wards and
      laboratory. The method has economic benefits for the health care system and
      community.

PMID- 9171259
TI  - Diabetes mellitus and interferon therapy.

PMID- 9171260
TI  - Is low-dose aspirin a useful adjuvant therapy in the treatment of NIDDM?

PMID- 9171261
TI  - Monounsaturated fat and postprandial triglyceride levels in non-insulin-dependent
      diabetic persons.

PMID- 9171262
TI  - Increased frequency of diabetic foot publications.

PMID- 9171263
TI  - Efficacy and indications of CSII revisited: the Hotel-Dieu cohort.

PMID- 9171264
TI  - A comparison of the cytology of endomyocardial biopsy washings from heart
      transplants with biopsy histologic study and peripheral blood lymphocyte counts.
AB  - Cytospin preparations of endomyocardial biopsy washings were examined on 117
      occasions from 13 heart transplant recipients and categorized according to the
      pattern of cell types observed. Twenty-nine percent of samples were acellular, a
      further 10% too bloodstained for analysis, and 61% were cellular. Eight
      lymphocytic samples were found and in all cases there was at least grade 1B
      rejection (four grade 1B, three grade 2, and one grade 3A) on histologic study.
      However, histologic study showed at least 1B rejection in 48% of cases when
      cytospins showed mixed inflammatory cells, 33% of cases when cytospins were
      histiocytic and in 35% when cytospins were bloodstained or acellular. Furthermore
      16 of these rejection episodes with nonlymphocytic cytospins were grade 2.
      Although the recovery of a lymphocytic cytospin was specific for rejection, the
      sensitivity of the test was poor. Even when the sample is adequate, this method
      of biopsy washings will predict only one third of cases of significant acute
      rejection (grade 2 or worse). The large proportion of unsuitable samples also
      severely limits the utility of endomyocardial biopsy washings for the diagnosis
      of rejection. Histiocytic cytospins were seen in 63% of samples when previous
      biopsy sites were reported on histologic study and also in all three samples when
      histologic study showed ischemic injury. A mixed inflammatory cell pattern was
      seen to a lesser extent (31% of samples) in relation to previous biopsy sites.
      High peripheral blood lymphocyte counts were found when endomyocardial biopsy
      washings were lymphocytic or mixed inflammatory and also when histologic study
      showed endocardial lymphocytic infiltration (Quilty effect).

PMID- 9171265
TI  - Different inhibitory effects of immunosuppressive drugs on human and rat aortic
      smooth muscle and endothelial cell proliferation stimulated by platelet-derived
      growth factor or endothelial cell growth factor.
AB  - BACKGROUND: Vascular smooth muscle cell hyperplasia with resulting luminal
      narrowing is the main histologic feature of accelerated arteriosclerosis seen
      after organ transplantation (transplant arteriosclerosis) and after balloon
      angioplasty (restenosis). It limits long-term allograft survival, as well as the
      success rate of angioplasty. At present, effective prophylactic and therapeutic
      strategies for these complications are still missing. Studies of in vivo models
      of accelerated arteriosclerosis induced by allogeneic or mechanical injury to the
      vasculature indicate that certain immunosuppressive drugs have inhibitory
      properties on smooth muscle cell hyperplasia. METHODS: This study summarizes the
      inhibitory effects of different immunosuppressive drugs in vitro on the growth
      factor-induced proliferation of vascular smooth muscle cells and endothelial
      cells isolated from human and rat thoracic aortas. RESULTS: The
      immunosuppressants rapamycin and mycophenolic acid were potent in inhibiting
      smooth muscle and endothelial cell proliferation. Cyclosporine demonstrated some
      inhibition of smooth muscle and endothelial cell proliferation, but the
      inhibitory concentration50 (IC50) values were just below toxicity levels. FK506
      revealed a moderate inhibitory activity but, interestingly, only for human cells.
      High concentrations of leflunomide inhibited in our experiments only rat smooth
      muscle and endothelial cell proliferation. Methylprednisolone showed a gradual
      inhibition over a broad concentration interval of rat and human smooth muscle
      cells and of rat but not of human endothelial cells. CONCLUSIONS: These data
      indicate that all of the established and new immunosuppressants tested have
      antiproliferative properties on vascular cells. Rapamycin was by far the most
      potent one. Therefore immunosuppressants, especiallyrapamycin and mycophenolic
      acid, may be used for prevention of accelerated arteriosclerosis.

PMID- 9171266
TI  - Inhibition of endothelial cell function: should this be a main goal of
      immunosuppressive strategies?

PMID- 9171267
TI  - Does distance between home and transplantation center adversely affect patient
      outcomes after heart transplantation?
AB  - BACKGROUND: The emergence of heart transplantation referral centers, in an era of
      cost-conscious managed care programs, frequently leads to long-distance patient
      consultation and care. The purpose of this project was to review one center's
      experience regarding the effect of long distances from home to transplantation
      hospital on outcomes. METHODS: Three hundred twelve adult, noninternational,
      transplant recipients surviving at least 3 months were assessed for 10 events:
      rejection episodes, number of endomyocardial biopsies, emergency department
      visits, hospital admissions, return to full-time work or school, infections,
      coronary allograft vasculopathy, malignancies, retransplantation, and death.
      Presence of a locally involved physician was also determined. Distance from the
      transplantation center was analyzed in three discrete groups: 0 to 150 miles (n =
      207), 151 to 300 miles (n = 69), and >300 miles (n = 36). RESULTS: There were no
      differences among the groups in mean length of follow-up (40.6, 36.9, 39.0
      months, p = 0.27) or number of biopsies (20.5 +/- 0.16, 18.3 +/- 1.1, 18.0 +/-
      1.1, p = 0.07). As the distance increased from the transplantation center, there
      was no greater incidence of adverse outcomes. Cellular rejection was the same
      among the groups (45%, 45%, 36%, p = 0.58). Likewise, emergency department visits
      and hospital admissions also did not vary: (9.7%, 5.8%, 8.3%, p = 0.61) and
      (22.2%, 13.0%, 16.7%, p = 0.23, respectively). There were no differences in the
      incidence of coronary vasculopathy (9.2%, 11.6%, 13.9%, p = 0.63). More
      importantly, the three groups did not differ in death/retransplantation rates (3
      year survival, 84.5, 94.0 and 86.9, p = 0.14). Patients cared for by a local
      physician in addition to their transplant cardiologist had better survival rates
      than patients without a local physician (3-year survival rate, 90.7 vs 72.6, p =
      0.0008). CONCLUSIONS: Long-distance management of heart transplant recipients is
      successful and is not associated with an increase in adverse outcomes. By itself,
      distance should not represent a contraindication to transplantation. Patients
      should be encouraged to maintain contact with a local physician, in addition to
      the regularly scheduled visits at the transplantation center.

PMID- 9171268
TI  - Assessment of early left ventricular remodeling in orthotopic heart transplant
      recipients with cine magnetic resonance imaging: potential mechanisms.
AB  - We performed short axis cine magnetic resonance imaging studies in 11 patients 2
      months after they underwent orthotopic heart transplantation (OHT), and in 10
      control subjects, to measure left ventricular (LV) volumes, mass, and end
      systolic wall stress to assess ventricular remodeling after OHT. Although there
      were no significant differences in ventricular volumes and ejection fractions
      between heart transplant recipients and control subjects, heart transplant
      recipients had significantly higher LV mass (198 +/- 61 vs 132 +/- 27 gm, p =
      0.001). As a consequence of myocardial hypertrophy, end-systolic wall stress was
      significantly reduced in heart transplant recipients compared with control
      subjects (34 +/- 16 vs 57 +/- 10 kdyne/cm2, p = 0.001). Moreover, heart
      transplant recipients had significantly reduced end-systolic wall stress/volume
      ratio when compared with control subjects (0.89 +/- 0.3 vs 1.26 +/- 0.3
      kdyne/cm2/ml, p < 0.01), indicating an already reduced LV contractility 2 months
      after heart transplantation. Univariate regression analysis revealed a
      significant correlation between LV mass and averaged cyclosporine levels, but no
      correlation between LV mass and blood pressure, cold ischemic time, acute
      rejection, age, body mass, blood pressure, plasma catecholamine levels, or plasma
      renin activity. Magnetic resonance imaging demonstrates early LV remodeling after
      OHT with reduced myocardial contractility. Cyclosporine may be contributing to
      these changes.

PMID- 9171269
TI  - Status of lung transplant recipients surviving beyond five years.
AB  - BACKGROUND: Prolonged survival after lung transplantation is now commonplace as a
      result of advances in surgical techniques and postoperative management protocols.
      Although 1- and 5-year functional and survival data after lung transplantation
      are well known, sparse information is available regarding functional status of
      recipients surviving beyond 5 years. METHODS: The medical records and pulmonary
      function study results of lung transplant recipients who had survived at least 5
      years as of September 1995 were retrospectively reviewed. RESULTS: Of the 76
      transplantations performed between November 1983 and September 1990, 30 (39.5%)
      were double lung transplantations, and 46 (60.5%) were single lung
      transplantations. Thirty-one recipients were alive 5 years after transplantation
      (12 double lung transplantations, 19 single lung transplantations). The 5-, 6-,
      and 7-year survival rates were 44%, 34%, and 29%, respectively. There was no
      association or difference in cytomegalovirus status, sex, and blood group between
      those who died within 5 years and those who survived beyond 5 years. The median
      percent predicted FEVs for single and double lung transplant recipients were as
      follows: 5 yrs-75%, 75%; 6 years-73%, 75%; 7 years-68%, 73%. The proportion of
      recipients with bronchiolitis obliterans syndrome according to published criteria
      was as follows: stage 0, 32%; stage I, 19%; stage II, 16%; and stage III, 19%.
      The functional status (i.e., active, working, disabled) 5 years after
      transplantation was as follows: active/working, 74%; active but not working, 13%;
      some limitation/independent, 10%; and disabled, 3%. CONCLUSION: Bronchiolitis
      obliterans syndrome is a frequent occurrence in long-term survivors.
      Nevertheless, in spite of this condition, most recipients have acceptable lung
      function, are active, and are generally working.

PMID- 9171270
TI  - Increased levels of circulating nitrates and impaired endothelium-mediated
      vasodilation suggest multiple roles of nitric oxide during acute rejection of
      pulmonary allografts.
AB  - Experiments were designed to determine whether changes in pulmonary artery
      function could be reduced by treatment with a lipid peroxidation inhibitor (H
      290/51) during acute rejection of pulmonary allografts. Single lung
      transplantation was performed in three groups of dogs: group 1 was maintained on
      immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group
      2, immunosuppression was discontinued on postoperative day 5, so that rejection
      occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression
      was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25
      mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma
      nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative
      day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and
      endothelium-dependent relaxations to adenosine diphosphate were reduced in
      pulmonary arteries from rejecting lungs. Responses of rings from dogs treated
      with H 290/51 were similar to those from rejecting lungs. Rejection did not alter
      relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased
      significantly during rejection independently of treatment with H 290/51. Results
      of this study confirm that endothelium-dependent relaxation of pulmonary arteries
      is reduced during acute rejection of lung allografts. The result extends these
      observations to suggest that treatment with a lipid peroxidation inhibitor
      neither protects the pulmonary artery function nor affects levels of circulating
      NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular
      changes associated with allograft rejection.

PMID- 9171271
TI  - Saprophytic fungal infections and lung transplantation--revisited.
AB  - BACKGROUND: Fungal infections cause serious morbidity and death in lung
      transplant recipients. Some centers exclude and others will prophylactically
      treat patients with evidence of Aspergillus colonization. METHODS: Of 126
      patients undergoing lung transplantation at the University of North Carolina
      since January 1990, five patients have died because of invasive Aspergillus and
      other saprophytic fungal infections. Those cases are reviewed looking for common
      predisposing factors, including any evidence of prior colonization. In addition,
      all preoperative and postoperative culture data on all transplant recipients were
      retrospectively examined to define the prevalence of preoperative and
      postoperative Aspergillus colonization in 121 patients with and without cystic
      fibrosis, none of whom had development of significant fungal disease. RESULTS:
      Fifty-two percent of 65 patients with cystic fibrosis were colonized with
      Aspergillus before operation, and 40% after operation at some time. None had
      development of significant Aspergillus infections, and none received prophylactic
      antifungal therapy. Most of the deaths from deep-seated fungal infections have
      been in patients without cystic fibrosis with no evidence of preoperative
      colonization. These patients had evidence of severe obliterative bronchiolitis,
      bacterial infections, persisting cytomegalovirus disease, or other major organ
      failure. CONCLUSION: The rationale for excluding patients or for giving
      amphotericin in the perioperative period in those patients who are colonized
      before surgery is questioned.

PMID- 9171272
TI  - Single lung transplantation for canine pulmonary hypertension.
AB  - BACKGROUND: In spite of recent reports of the clinical application of single lung
      transplantation for pulmonary hypertension, there is little underlying
      experimental data because of the lack of a reliable animal pulmonary hypertensive
      transplant model. We have established a pulmonary hypertensive model in beagles
      with dehydromonocrotaline and have been able to measure cardiopulmonary
      hemodynamics accurately and use circulatory assists during procedures. The
      purpose of this study was to determine whether single lung transplantation could
      be performed after the protocol of clinical procedure. METHODS AND RESULTS: In
      six control dogs, allografting was successfully completed without cardiopulmonary
      bypass. Because one pulmonary hypertensive recipient dog died of right
      ventricular failure during the procedure without cardiopulmonary bypass, we used
      bypass for allografting in five pulmonary hypertensive dogs. Cardiopulmonary
      bypass lowered pulmonary artery pressure, allowing pulmonary arterial clamping
      and avoiding right ventricular overload. All pulmonary hypertensive dogs
      undergoing bypass were successfully weaned from bypass, indicating a good
      hemodynamic response to transplantation. In pulmonary hypertensive dogs,
      transplantation resulted in significant decreases in systolic pulmonary artery
      pressure and pulmonary vascular resistance, and a significant increase in blood
      flow to the graft lung, whereas in controls the results were the reverse.
      CONCLUSIONS: Thus we were able to show that hemodynamics improved after single
      lung transplantation with cardiopulmonary bypass in a new pulmonary hypertensive
      animal model. These relatively larger animals are valuable for further studies of
      single, double, bilateral, and heart-lung transplantation for pulmonary
      hypertension.

PMID- 9171274
TI  - Predictors and determinants of hospital length of stay in congestive heart
      failure in ten community hospitals.
AB  - BACKGROUND: Little is known about the actual determinants of hospital length of
      stay (LOS) among patients admitted with congestive heart failure (CHF), in spite
      of its economic impact. To increase understanding of these factors, we examined
      the demographic, clinical, laboratory, and treatment characteristics of patients
      hospitalized with decompensated CHF. METHODS: The charts of consecutive patients
      admitted to 10 acute care community hospitals during 1995 were reviewed. The
      relationship between LOS and more than 140 patient-specific variables were
      examined. First, patient characteristics identifiable within the first 24 hours
      of hospitalization were examined for their relationship with LOS. Then, variables
      indicative of the processes of care and response to treatment were studied.
      Finally, administrative data were added to yield the final model for LOS.
      RESULTS: During the study period 1402 patients were admitted to the participating
      centers. The patients were predominantly elderly with moderately severe or severe
      CHF. With stepwise multiple linear regression, 5% of the variation in LOS could
      be explained by baseline characteristics alone (r = 0.22, p < 0.0001). When
      treatment and response variables were added to this model, 15% of the variation
      in LOS could be explained (r = 0.39, p < 0.0001). When administrative data were
      added, the final model explained 31% of the variation in LOS (r = 0.56, p <
      0.0001). CONCLUSIONS: We conclude that LOS among patients hospitalized with
      decompensated CHF is partially related to patient demographics, severity of
      illness, management modalities, response to treatment, and administrative data.
      However, significant residual variation in LOS exists, which cannot be explained
      by these factors. These observations may be of value in the design and
      implementation of initiatives aimed at reducing resource utilization and
      improving quality of care in CHF.

PMID- 9171273
TI  - An adult canine model of chronic pulmonary hypertension for cardiopulmonary
      transplantation.
AB  - BACKGROUND: This study establishes a chemically-induced canine model of chronic
      pulmonary hypertension (CPH) using monocrotaline pyrrole (MCTP) and then
      characterizes this model in terms of hemodynamic, morphologic, and cardiac
      functional changes. METHODS: Thirty-three adult mongrel dogs (22 to 25 kg) were
      used. All animals underwent pulmonary artery catheterization to measure central
      venous pressure, mean right ventricular pressure (mRVP), mean pulmonary artery
      pressure (mPAP), and pulmonary capillary wedge pressure before and 6 weeks after
      a right atrial injection of either 60 mg/kg monocrotaline (group A, n = 8), 5
      mg/kg MCTP (group B, n = 4), 3 mg/kg MCTP (group C, n = 13) or placebo (control,
      n = 8). Six weeks after injection, hearts in control and group C dogs were
      instrumented with flow probes, dimension transducers, and micromanometers to
      measure dynamic ventricular pressures and volumes. RESULTS: No significant
      differences in baseline hemodynamic indexes were observed between groups. All
      animals in group B and five in group C died after MCTP injection as a result of
      pulmonary edema. No significant increase in any hemodynamic parameters occurred
      in group A or in control dogs 6 weeks after injection. In group C, significant
      increases in central venous pressure, mRVP, and mPAP were observed 6 weeks after
      injection. Significant increases in right ventricular (RV) function and the
      weight ratio of the RV to left ventricle were observed in group C when compared
      with controls. CONCLUSIONS: A chemically-induced canine model of CPH has been
      created. Significant increases in mRVP, mPAP, and pulmonary capillary wedge
      pressure were observed 6 weeks after MCTP injection. RV function adapts to the
      increased afterload in the short term without evidence of failure. A stable model
      of pulmonary hypertension is provided as a potential means to evaluate
      posttransplantation RV dysfunction in the setting of CPH.

PMID- 9171275
TI  - Hemodynamic and neurohumoral effects of long-term prostaglandin E1 infusions in
      outpatients with severe congestive heart failure.
AB  - BACKGROUND: Prostaglandins of the E type are potent endogenous vasodilators that
      also interfere with the activity of the sympathetic nervous system. Thus treating
      patients with end-stage heart failure with prostaglandin E1 (PGE1) infusions
      seems to accord well with the hypothesis that neurohumoral imbalance rather than
      hemodynamic derangements should be the priority in the treatment of heart
      failure. METHODS: We sought to investigate neurohumoral in addition to
      hemodynamic changes during long-term PGE1 infusion and determined plasma renin
      activity, atrial natriuretic peptide, norepinephrine, and big endothelin plasma
      levels in 13 male patients with heart failure whose symptoms remained severe in
      spite of optimized oral therapy with digitalis, nitrates, furosemide (185 +/- 72
      mg/d) and enalapril (33 +/- 3 mg/d). PGE1 infusion rate was started with 2.5
      ng/kg/min and stepwise increased to the maximum tolerated dose (26 +/- 4
      ng/kg/min), which was halved for continuous infusion through the following 12
      hours and further stepwise reduced to an average dose of 8 +/- 1 ng/kg/min. Right
      heart catheterization was performed for acute hemodynamic studies and after 4
      weeks. All patients were discharged with a catheter that was connected to a
      portable pump for home therapy. RESULTS: Acute effects of PGE1 were reductions in
      systemic blood pressure, (p < 0.05), right atrial pressure (p < 0.001), pulmonary
      artery pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.01),
      systemic and pulmonary vascular resistance index (both p < 0.01) and an increase
      in cardiac and stroke volume index (both p < 0.001) without a change in heart
      rate. After 4 weeks a persistent increase from baseline in cardiac index (from
      1.9 +/- 0.1 to 2.5 +/- 0.2 L/min/m2; p < 0.01) and in pulmonary vascular
      resistance index (from 479 +/- 50 to 331 +/- 29 dynes x sec/cm5 x m2; p < 0.05)
      was observed. Atrial natriuretic peptide (p < 0.05) decreased, and norepinephrine
      and big endothelin showed a tendency to a lower level. Concomitantly, New York
      Heart Association functional class changed (p = 0.0001), with one patient's
      condition remaining class IV, the conditions of seven patients decreasing to
      class II, and the conditions of five patients decreasing to class III.
      CONCLUSION: Thus long-term parenteral home therapy with PGE1 infusions in
      patients with severe end-stage heart failure elicited beneficial clinical and
      hemodynamic effects without activating neurohumoral counterregulatory systems.

PMID- 9171276
TI  - Defining obesity in patients undergoing orthotopic heart transplantation: body
      mass index versus percent body fat.
AB  - We examined body mass index (BMI) as a proxy for percent body fat among 26 men
      and women successfully undergoing orthotopic heart transplantation. Percent body
      fat was determined by use of bioelectrical impedance techniques. We found that,
      although BMI was well correlated with percent body fat (r = 0.58, p < 0.01), use
      of a BMI of greater than 27 kg/m2 to define obesity potentially misclassified
      patients when compared with defining obesity as a percentage of body fat as both
      greater than 30% (BMI = 9 of 26 patients vs percent body fat = 6 of 26 patients)
      and greater than 40% (BMI = 9 of 26 versus percent body fat = 1 of 9). We
      conclude that percent body fat measurements are more methodologically appropriate
      means for J Heart Lung Transplant 1997;16:563-5.

PMID- 9171277
TI  - Diaphragmatic dysfunction after heart or lung transplantation.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence and outcome of
      diaphragmatic dysfunction in patients after heart or lung transplantation and to
      assess the value of bedside sonography for the detection of diaphragmatic
      dysfunction. METHODS: We prospectively evaluated 33 heart transplant recipients
      and 27 lung transplant recipients by use of sonography of the diaphragm and
      fluoroscopy. RESULTS: Diaphragmatic dysfunction, diagnosed with ultrasonography
      and confirmed with fluoroscopy, was present in four heart transplant recipients
      (12.1%) and two lung transplant recipients (7.4%) and such dysfunction led to a
      statistically significant higher incidence of pneumonia during hospitalization
      and a nonstatistically significant increased length of intubation compared with
      patients with normal diaphragmatic function. CONCLUSION: Diaphragmatic
      dysfunction, which can be reliably diagnosed with bedside sonography, is common
      after heart and lung transplantation and seems to have a negative influence on
      patient recovery.

PMID- 9171278
TI  - Donor-specific anti-human leukocyte antigen class I antibodies after implantation
      of cardiac valve allografts.
AB  - The allospecific humoral immune response was examined in 31 patients in the first
      year after implantation of cryopreserved human cardiac valves. We determined the
      percentage antibodies against human leucocyte antigens (HLA) class I in a
      complement-dependent microlymphocytotoxicity test against a panel of 50 selected
      donors carrying most of the defined HLA-A and HLA-B specificities (panel-reactive
      antibodies). In blood samples taken immediately before implantation, no
      antibodies could be detected. Thereafter, antibodies were present in 23 of 31
      (74%) patients (median panel-reactive antibodies: 57%, range 9% to 91%). In 21
      patients the HLA-type of the valve donor was available. In four patients no blood
      samples taken after 4 weeks were available. In 14 of 17 patients (82%) with a
      follow-up of more than 1 month antibodies were present, and in 12 of these 14
      (86%) antibodies were specifically directed against HLA class I of the donor. In
      conclusion, the formation of donor-specific antibodies is frequently observed
      after human cardiac valve replacement. It could be one of the factors leading to
      valve destruction and dysfunction.

PMID- 9171279
TI  - Combined orthotopic heart and liver transplantation for genetic hemochromatosis.
AB  - A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and
      class IV congestive heart failure caused by genetic hemochromatosis underwent
      combined orthotopic heart and liver transplantation. The patient remains well,
      working full time, 4 years after operation. Combined heart and liver
      transplantation is an effective therapy for selected patients with concurrent
      heart and liver failure caused by systemic iron overload.

PMID- 9171280
TI  - External jugular vein approach for percutaneous right ventricular biopsy.
AB  - A technique of external jugular venous cannulation for right ventricular
      endomyocardial biopsy is described. This often underused approach for venous
      access warrants consideration in patients at high risk for bleeding
      complications, pneumothorax, or difficult internal jugular access who require
      biopsy.

PMID- 9171281
TI  - Rapid resolution of gingival hyperplasia after switching from cyclosporine A to
      tacrolimus.

PMID- 9171282
TI  - The nuiA gene from Anabaena sp. encoding an inhibitor of the NucA sugar-non
      specific nuclease.
AB  - Many filamentous, heterocyst-forming cyanobacteria express a sugar-non-specific
      nuclease of about 29 kDa that can be detected in DNA-containing SDS-PAGE gels.
      The nucA gene encoding this nuclease has previously been cloned from Anabaena sp.
      PCC 7120, sequenced and expressed in Escherichia coli. The NucA protein bears a
      putative signal peptide close to its N-terminal end and, in Anabaena cultures, is
      present in both the cells and the extracellular medium. Cell-free extracts of
      different cyanobacteria producing NucA-like nucleases exhibited an inhibitory
      activity on NucA. In Anabaena sp. PCC 7120, this inhibition was exerted by
      protein(s) or protein-containing molecule(s) that were heat resistant.
      Immediately downstream from the nucA gene, in the complementary strand, we have
      identified an open reading frame composed of 135 codons, that we have named nuiA,
      whose expression in E. coli conferred heat-resistant NucA-inhibitory activity to
      cell-free extracts. The NuiA protein was purified to homogeneity, and purified
      NuiA inhibited the nuclease activity of NucA. Sequences hybridizing with the nuiA
      gene have been found in all the tested cyanobacterial strains that express a NucA
      like nuclease. Whereas the NucA protein is homologous to endonuclease G from
      vertebrates and to nucleases from Serratia marcescens and yeast, no protein
      homologous to NuiA was found in the available databases. Therefore, nuiA
      represents a novel gene encoding a nuclease inhibitor.

PMID- 9171283
TI  - Identification of a novel type 1 diabetes-specific epitope by screening phage
      libraries with sera from pre-diabetic patients.
AB  - We used random peptide libraries displayed on phage to search for ligands to
      insulin dependent diabetes mellitus-related antibodies and were able to identify
      several candidate disease-related peptides. One of them, clone 92, showed a
      significant difference in the frequency of reactivity with the sera of patients
      and normal controls. Human immunoglobulins immunopurified on phage 92
      specifically stained the islets on human pancreatic sections. When injected into
      rabbits, the selected peptide elicited antibodies that also stained human and rat
      pancreatic sections, with a pattern similar to that observed with immunoglobulins
      purified from the sera of patients. No reactivity was observed in other tissues.
      Our results indicate that the peptide identified in this work mimics a novel,
      diabetes-related self-antigen.

PMID- 9171284
TI  - Selectively-infective phage (SIP): a mechanistic dissection of a novel in vivo
      selection for protein-ligand interactions.
AB  - Selectively-infective phage (SIP) is a novel methodology for the in vivo
      selection of interacting protein-ligand pairs. It consists of two components, (1)
      a phage particle made non-infective by replacing its N-terminal domains of
      geneIII protein (gIIIp) with a ligand-binding protein, and (2) an "adapter"
      molecule in which the ligand is linked to those N-terminal domains of gIIIp which
      are missing from the phage particle. Infectivity is restored when the displayed
      protein binds to the ligand and thereby attaches the missing N-terminal domains
      of gIIIp to the phage particle. Phage propagation is thus strictly dependent on
      the protein-ligand interaction. We have shown that the insertion of beta
      lactamase into different positions of gIIIp, mimicking the insertion of a protein
      ligand pair, led to highly infective phage particles. Any phages lacking the
      first N-terminal domain were not infective at all. In contrast, those lacking
      only the second N-terminal domain showed low infectivity irrespective of the
      presence or absence of the F-pilus on the recipient cell, which could be enhanced
      by addition of calcium. An anti-fluorescein scFv antibody and its antigen
      fluorescein were examined as a protein-ligand model system for SIP experiments.
      Adapter molecules, synthesized by chemical coupling of fluorescein to the
      purified N-terminal domains, were mixed with non-infective anti-fluorescein scFv
      displaying phages. Infection events were strictly dependent on fluorescein being
      coupled to the N-terminal domains and showed a strong dependence on the adapter
      concentration. Up to 10(6) antigen-specific events could be obtained from 10(10)
      input phages, compared to only one antigen-independent event. Since no separation
      of binders and non-binders is necessary, SIP is promising as a rapid procedure to
      select for high affinity interactions.

PMID- 9171285
TI  - Expression patterns and transcript processing of ftt-1 and ftt-2, two C. elegans
      14-3-3 homologues.
AB  - A wide diversity of biological functions have been attributed to the highly
      conserved and ubiquitous 14-3-3 protein family. Yet how much of this diversity is
      inherent in the basic structure of 14-3-3 and how much is due to isoform specific
      functions is not yet fully understood. Here, two Caenorhabditis elegans 14-3-3
      isoforms whose protein sequences are 90% similar were found to differ
      significantly in both their genomic structure and expression patterns. The two
      genes, ftt-1 (IV) (fourteen-three-three) and ftt-2 (X), differ in both the
      position and sequence of their introns. Since the various intron/exon boundaries
      respect neither functional nor structural protein motifs, the introns appear to
      be relatively recent evolutionary additions. ftt-1(IV) encodes three germline
      enhanced transcripts, two of which are related through the differential use of
      alternative poly(A) addition sites. RNA in situ hybridization studies reveal high
      levels of ftt-1 throughout the gonad with particularly high levels in the distal
      arm. In contrast, ftt-2 (X) encodes a single transcript which is expressed
      somatically. In embryos, high levels of ftt-1 transcripts appear to be maternally
      supplied, whereas ftt-2 is expressed as an early zygotic transcript whose
      expression pattern later localizes to the posterior region of post-proliferative
      embryos. These expression pattern differences between ftt-1 and ftt-2 suggest
      that these two 14-3-3 isoforms perform distinct biological roles within the worm.

PMID- 9171286
TI  - Small-molecule-substrate interactions with a self-aminoacylating ribozyme.
AB  - A self-aminoacylating RNA catalyst is shown to carry out the chemistry required
      for turnover, being reacylated several times from aminoacyl-AMP with an unaltered
      rate, thereby meeting one definition of an enzyme. Furthermore, a newly applied
      gel electrophoresis assay suggests first order kinetics in RNA and saturation
      kinetics in the substrate aminoacyl-adenylate, implying a Michaelis complex. AMP
      is a competitive inhibitor, though phenylalanine is not detectably inhibitory,
      consistent with a Michaelis complex through the AMP moiety of phenylalanyl
      adenylate substrate. This idea is supported by measurement of elevated acylation
      velocities with seryl and alanyl-adenylates. The rate of aminoacylation increases
      with pH, consistent with attack of a terminal ribose oxyanion on the carbonyl
      carbon atom of the adenylate.

PMID- 9171287
TI  - Recognition of tRNA(Gly) by three widely diverged glycyl-tRNA synthetases.
AB  - Glycyl-tRNA synthetase (GlyRS) is an unusual aminoacyl-tRNA synthetase because it
      varies in its quarternary structure between organisms; Escherichia coli GlyRS is
      an alpha2beta2 tetramer, whereas those of Thermus thermophilus and yeast are
      alpha2 dimers. In contrast, the tRNA(Gly) sequence is virtually identical in E.
      coli and T. thermophilus but very different in yeast. In this study, we examined
      the molecular recognition of tRNA(Gly) by three widely diverged GlyRSs using in
      vitro tRNA transcripts. Mutation studies showed that the discriminator base at
      position 73, the second base-pair, C2 x G71, in the acceptor stem, and the
      anticodon nucleotides, C35 and C36, contribute to the specific aminoacylation of
      all three GlyRSs, the discriminator base differing between prokaryotes (U73) and
      eukaryotes (A73). However, we found differences between yeast and two bacteria
      around the second base-pair in the acceptor stem. The first base-pair, G1 x C72,
      is important for glycylation in E. coli and T. thermophilus, whereas the third
      base-pair, G3 x C70, is important for glycylation in yeast. These findings
      indicate that despite such large differences of the two prokaryotic GlyRSs,
      tRNA(Gly) identity has been essentially conserved in prokaryotes, and that there
      are also differences in the acceptor stem recognition between prokaryotes and
      yeast. The clear separation between prokaryotes and yeast is retained in the
      identity element location, whereas the apparent diversity of the two prokaryotic
      enzymes does not reflect on the tRNA recognition.

PMID- 9171288
TI  - Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 RT and
      HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer.
AB  - Mutations that confer resistance to nucleoside analogs do not cluster around the
      deoxynucleotide triphosphate (dNTP) binding site. Instead, these mutations appear
      to lie along the groove in the enzyme where the template-primer binds. Based on
      such structural data and on complementary biochemical analyses, it has been
      suggested that resistance to nucleoside analogs involves repositioning of the
      template-primer. We have prepared mutations in HIV-2 RT that are the homologs of
      mutations that confer resistance to nucleoside analogs in HIV-1 RT. Analysis of
      the behavior of HIV-2 RT mutants (Leu74Val, Glu89Gly, Ser215Tyr,
      Leu74Val/Ser215Tyr and Glu89Gly/Ser215Tyr) in vitro confirms the results obtained
      with HIV-1 RT: resistance is a function of the length of the template overhang.
      These analyses also suggest that the homolog in HIV-2 RT of one of the mutations
      that confers resistance to AZT in HIV-1 RT (Thr215Tyr) confers resistance by
      repositioning of the template-primer.

PMID- 9171289
TI  - Bacteriophage P22 scaffolding protein forms oligomers in solution.
AB  - The scaffolding protein of Salmonella typhimurium bacteriophage P22 is a 33.6 kDa
      protein required both in vivo and in vitro for the polymerization of the viral
      coat protein into closed T = 7 icosahedral procapsids. In vitro assembly reaction
      kinetics have previously been found to vary between second and third order with
      respect to scaffolding protein concentration, suggesting that dimers and/or
      higher-order oligomers may be the active species in assembly. Analytical
      ultracentrifugation experiments suggest that scaffolding protein undergoes a
      rapidly-reversible monomer/dimer/tetramer equilibrium, with higher association
      constants at 4 degrees C than at 20 degrees C. Under conditions in which in vitro
      assembly reactions are carried out (30 to 1000 microg/ml scaffolding protein, 20
      degrees C), monomers are the predominant species, but the concentration of dimers
      is significant. A mutant scaffolding protein, R74C/L177I, which forms disulfide
      linked dimers, catalyzed procapsid assembly at a higher rate than did the wild
      type scaffolding protein; preincubation in dithiothreitol had little effect on
      the wild-type protein, but greatly reduced the activity of the mutant. These
      findings suggest that dimers and/or higher-order oligomers of scaffolding protein
      are active species in the assembly of P22.

PMID- 9171290
TI  - Solution structure of R-elafin, a specific inhibitor of elastase.
AB  - The solution structure of r-elafin, a specific elastase inhibitor, has been
      determined using NMR spectroscopy. Characterized by a flat core and a flexible N
      terminal extremity, the three-dimensional structure is formed by a central
      twisted beta-hairpin accompanied by two external segments linked by the
      proteinase binding loop. A cluster of three disulfide bridges connects the
      external segments to the central beta-sheet and a single fourth disulfide bridge
      links the binding loop to the central beta-turn. The same spatial distribution of
      disulfide bridges can be observed in both domains of the secretory leukocyte
      protease inhibitor (SLPI), another elastase inhibitor. The structural homology
      between r-elafin and the C-terminal domain of SLPI confirms the former as a
      second member of the chelonianin family of proteinase inhibitors. Based on the
      homology between the two proteins and recent results obtained for elastase
      binding mutants of the bovine pancreatic trypsin inhibitor (BPTI), we define the
      segment 22 to 27 as the binding loop of elafin, with the scissile peptide bond
      between Ala24 and Met25. In our solution structures, this loop is extended and
      solvent-exposed, and exhibits a large degree of flexibility. This mobility,
      already observed for the binding loop in other protease inhibitors in solution,
      might be an important feature for the interaction with the corresponding
      protease.

PMID- 9171291
TI  - Contact area difference (CAD): a robust measure to evaluate accuracy of protein
      models.
AB  - A simple unified measure to evaluate the accuracy of three-dimensional atomic
      protein models is proposed. This measure is a normalized sum of absolute
      differences of residue-residue contact surface areas calculated for a reference
      structure and a model. It employs more rigorous quantitative evaluation of a
      contact than previously used contact measures. We argue that the contact area
      difference (CAD) number is a robust single measure to evaluate protein structure
      predictions in a wide range of model accuracies, from ab initio and threading
      models to models by homology, since it reflects both backbone topology and side
      chain packing, is smooth, continuous and threshold-free, is not sensitive to
      typical crystallographic errors and ambiguities, adequately penalizes domain
      and/or secondary structure rearrangements and protein plasticity, and has
      consistent linear and matrix representations for more detailed analysis. The CAD
      quality of crystallographic structures, NMR structures, models by homology, and
      unfolded and misfolded structures is evaluated. It is shown that the CAD number
      discriminates between models better than Cartesian root-mean-square deviation
      (cRMSD). Structural variability of the NMR structures was found to be three times
      larger than deformations of crystallographic structures in different packing
      environments.

PMID- 9171292
TI  - Adequacy of hemodialysis 1996.

PMID- 9171293
TI  - Remnant-like particle cholesterol may indicate atherogenic risk in patients on
      chronic hemodialysis.
AB  - Recently, involvement of remnant-like particle cholesterol (RLP-C) in
      atherosclerosis was reported, but this parameter has not been adequately
      investigated in hemodialysis (HD) patients. The present study investigated the
      relationship between the RLP-C level and total cholesterol (TC), triglycerides
      (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein
      cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein
      (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein
      (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum
      lipoproteins were determined by disk polyacrylamide gel electrophoresis. The
      relationship between the RLP-C level and three atherogenic indices was also
      studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly
      higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a
      significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB,
      VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However,
      there was no correlation with age or the duration of HD. RLP-C also showed
      significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL
      + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio.
      These results suggest that RLP-C may be a potential indicator of atherogenic risk
      in HD patients.

PMID- 9171294
TI  - Activated clotting time is not a sensitive parameter to monitor anticoagulation
      with low molecular weight heparin in hemodialysis.
AB  - To study whether the activated clotting time (ACT) is a sensitive parameter to
      monitor anticoagulation with low molecular weight heparin (LMWH) during
      hemodialysis, ACT, polymorphonuclear granulocyte-elastase, and anti-factor Xa
      activity were studied during 30 dialysis treatments with LMWH (35 IU/kg body
      weight bolus; 10 IU/h/kg). Twenty treatments were performed with Hemophan, ten
      with polysulfone dialyzers. No clinically relevant clotting of dialyzers was
      observed, but minimal fibrin deposition was found more often in the Hemophan
      group (50 vs. 30%). Despite continuously elevated anti-factor Xa levels (Hemophan
      0.49 +/- 0.03, polysulfone 0.62 +/- 0.01 IU/ml), a significant increase of ACT
      was only demonstrated 10 min after bolus application in the Hemophan group.
      Elevated polymorphonuclear granulocyte-elastase levels were demonstrated in the
      Hemophan group but were linked to the presence of minimal fibrin deposits and not
      to the dialyzer material. We conclude that ACT is not a sensitive parameter to
      monitor anticoagulation with standard doses of LMWH.

PMID- 9171295
TI  - Intracellular free magnesium concentrations in skeletal muscle in chronic
      uraemia.
AB  - Low intracellular free magnesium concentrations ([Mg2+]i) are associated with
      essential hypertension and may reflect a disordered cellular ionic environment.
      31P magnetic resonance spectroscopy was used to study skeletal muscle [Mg2+]i in
      a group of chronic renal failure (CRF) patients and data were compared with a
      group of control subjects of similar age. Other data including the patients'
      blood pressure, medication and plasma biochemistry were collected. There was a
      significant inverse correlation of [Mg2+]i with systolic (p < 0.001) and
      diastolic blood pressure (p < 0.05) in the CRF population. In CRF [Mg2+]i was
      similar (0.52 +/- 0.01 mM, SEM) to controls (0.53 +/- 0.01 mM; p = 0.20), even if
      just the normotensive patients and controls were compared. There was no
      correlation of [Mg2+]i with plasma parathyroid hormone, total [Mg2+] or [Ca2+].
      Similar to studies in subjects with essential hypertension, these data support a
      role for [Mg2+]i specifically, and an abnormal intracellular environment more
      generally, in the pathophysiology of hypertension in CRF.

PMID- 9171296
TI  - Increased production of interleukin-1beta and interleukin-1 receptor antagonist
      by peripheral blood mononuclear cells in undialyzed chronic renal failure.
AB  - We investigated the cell content and production of IL-1beta and IL-1 receptor
      antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated
      peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients
      with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on
      chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured
      by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not
      detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml,
      p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly
      higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured
      PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and
      in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the
      controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of
      IL-1Ra in the three groups was not significantly different. In LPS-stimulated
      PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in
      HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the
      controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC
      in the three groups was not significantly different. Moreover, the spontaneous IL
      1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/-
      19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The
      present study demonstrates that cytokine production by PBMC in undialyzed CRF
      patients as well as in hemodialyzed patients is heightened and may induce
      impaired function of the immunological system before CRF patients are introduced
      to dialysis.

PMID- 9171298
TI  - Djenkol beans as a cause of hematuria in children.
AB  - BACKGROUND: Djenkolism is djenkol bean poisoning, characterized by acute renal
      failure, urinary obstruction and spasmodic pain. The effects of djenkol bean
      consumption on the urinary tract without overt symptoms and long-term outcome are
      not established. This paper examines the association between djenkol bean
      ingestion and urine abnormalities in school children. METHOD: 609 school children
      aged 7-11 years in five urban Hat-Yai schools were interviewed, and had their
      urine analyzed. All children included in the study had normal blood pressure for
      age, no illness (including respiratory tract symptoms) and were not taking
      medication. RESULTS: 78% of the children had a history of eating djenkol bean and
      of these 31% had done so in the past 24 h. Children with hematuria were almost
      four times (crude odds ratio = 3.7) as likely to have a history of eating djenkol
      beans as those with normal urine. Crystaluria and pyuria were not significantly
      more common among those eating the beans. The risk of having hematuria did not
      change with increasing consumption, or time since last eaten, or type of
      preparation even after adjustment for sex and age. CONCLUSION: Djenkol bean
      consumption may be defined as one of the probable causes of hematuria in the area
      where the djenkol tree grows.

PMID- 9171297
TI  - Expression of glomerular antioxidant enzymes in human glomerulonephritis.
AB  - Increased oxidative stress can be correlated with glomerular injury. By
      immunohistochemical studies, we found expression of glomerular antioxidant
      enzymes (AOEs), including CuZn-superoxide dismutase (SOD), Mn-SOD, and catalase,
      in a wide variety of glomerular diseases. The distribution of the AOEs was either
      localized the in mesangial region or along the luminal surface or epithelial
      surface of the glomerular capillary wall. There was no significant difference of
      glomerular AOE expression among minimal change disease (MCD), IgM nephropathy
      (IgM N), focal segmental glomerulosclerosis, and membranous glomerulonephritis
      (MGN). However, when compared with MCD, IgM N and MGN, the glomerulus of lupus
      nephritis and IgA nephropathy expressed a significantly higher positive rate of
      AOEs (p = 0.04-0.002). The expression of AOEs had a trend to be associated with
      increased proliferative cell nuclear antigen-positive cells in the glomerulus of
      diffuse proliferative lupus nephritis (p = 0.056). No association was found
      between infiltrating leukocytes and AOE expression in all the disease groups. The
      glomerulus in kidneys with renal cell carcinoma expressed a significantly higher
      positive rate of AOEs and therefore could not be regarded as a normal control
      group. In summary, the immunohistochemical evidence of glomerular AOE expression
      in this study provides supporting evidence of oxidative stress in a wide variety
      of glomerular diseases.

PMID- 9171299
TI  - The transplanted nephronic mass influences renal vascular resistance and blood
      flow of the kidney graft.
AB  - In order to assess whether the transplanted nephronic mass plays a role in the
      progression of chronic graft dysfunction, 83 well-functioning renal transplants
      were investigated. Plasma creatinine, creatinine clearance, renal volume, blood
      flow and renal vascular resistance were measured. The weight of the donor was
      considered as an index of the transplanted renal parenchyma and the weight of the
      recipient as an index of the required nephronic mass. To evaluate the adequacy of
      the transplanted nephronic mass, the ratio between the donor and the recipient's
      weight was calculated. This ratio showed a mean of 1.06 +/- 0.18 and a range
      between 0.63 and 1.6, indicating that a parenchymal mass between 30 and 80% of
      the physiologic one was transplanted in these subjects. Patients were divided
      into two groups: group A patients with a ratio > 1, group B patients with a ratio
      < 1. In group A, a regression analysis did not show any relationship between
      transplant age and creatinine clearance, renal volume, blood flow and renal
      vascular resistance as assessed by echo-color-Doppler ultrasonography. In
      patients with reduced nephronic mass, group B, there was a negative relationship
      between renal blood flow and transplant duration (p = 0.03) and a positive
      relationship between transplant age and renal vascular resistance (p = 0.01) and
      renal volume (p = 0.01). These data support the hypothesis that the difference in
      weight between donor and recipient may influence the outcome of the graft.

PMID- 9171300
TI  - Impact of ganciclovir prophylaxis on cytomegalovirus infection in recipients of
      cadaveric renal allografts.
AB  - Cytomegalovirus (CMV) infection is a major cause of morbidity and occasionally of
      mortality in immunosuppressed allograft recipients. At the University of
      Cincinnati Medical Center, ganciclovir has been administered for the prevention
      of CMV infection since July 1992. Forty-six recipients of cadaveric renal
      allografts (Group I) received ganciclovir at a dose of 2.5 or 5 mg/kg/day
      (adjusted for renal function) for 14-21 days, during induction treatment and
      during antirejection treatment with monoclonal or polyclonal antilymphocyte
      preparations. In this retrospective study, these 46 patients were compared with
      77 recipients of cadaveric renal allografts transplanted prior to July 1992
      (Group II) for the prevalence, severity and time of CMV occurrence after
      transplantation. CMV diagnosis was based on clinical evaluation and was confirmed
      by blood cultures, CMV antigen immunofluorescence assay and/or histology.
      Patients were stratified according to CMV serology (+) or (-) in donor and
      recipient. CMV infection developed in 16 of 46 (35%) patients in Group I vs. 27
      of 77 (35%) patients in Group II (p = 0.97). A total of 25 episodes of CMV
      infection occurred in Group I compared to 44 in Group II (p = 0.76). CMV
      infection was diagnosed an average of 97.4 days after transplant in Group I
      compared to 48.3 days in Group II (p = 0.0003). Tissue-invasive CMV infection
      occurred in 3 patients in Group I (19%) vs. 12 in Group II (44%) (p = 0.5). In
      conclusion, ganciclovir prophylaxis resulted in a delayed onset of clinical CMV
      infection with a trend towards less severe infection in patients treated with
      antilymphocyte antibody preparations.

PMID- 9171301
TI  - Hypercoagulability and secondary hyperfibrinolysis may be related to abnormal
      lipid metabolism in patients treated with continuous ambulatory peritoneal
      dialysis.
AB  - To investigate abnormalities in the hemostatic and fibrinolytic system in CAPD
      patients, parameters of coagulation, anticoagulation, fibrinolysis, and platelet
      function were measured in 21 CAPD patients and 20 healthy controls. The CAPD
      patients had significantly higher levels of factor (F) IX, FVII, FX, antithrombin
      III, thrombin/antithrombin III complex, protein C, protein S, thrombomodulin,
      fibrinogen, fibrinopeptide A, plasminogen, FXIII, alpha2-plasmin inhibitor,
      alpha2-plasmin inhibitor/plasmin complex, D-dimer, fibrinopeptide B beta 15-42,
      and beta-thromboglobin than the healthy controls. The CAPD patients also showed a
      shorter prothrombin time. However, tissue plasminogen activator, plasminogen
      activator inhibitor-1 and platelet factor-4 did not show any significant
      differences from the levels in healthy controls. There was a significant positive
      correlation between many of the blood parameters and serum lipids. These results
      demonstrate that hypercoagulability and secondary hyperfibrinolysis occur in CAPD
      patients, and suggest that these changes may be related to abnormalities in lipid
      metabolism.

PMID- 9171302
TI  - Early increase of chondroitin sulfate glycosaminoglycan in the glomerular
      basement membrane of rats with diabetic glomerulopathy.
AB  - A decrease in anionic change and the loss of heparan sulfate proteoglycan have
      previously been observed in the glomerular basement membrane (GBM) during
      diabetic glomerulosclerosis. We studied the chronological changes in the anionic
      character and the glycosaminoglycan content in the GBM of WBN/ Kob rats with
      spontaneous diabetes. Two types of cationic probes were used: polyethyleneimine
      (PEI) and cationic colloidal gold (CCG). Immunogold labeling was performed with
      anti-monoclonal-heparan-sulfate-glycosaminoglycan (HS-GAG) and anti-chondroitin
      sulfate-glycosaminoglycan (CS-GAG) antibodies. The GBM width, the anionic sites
      and the GAG sites were investigated in diabetic WBN/Kob rats at 2, 10 and 19
      months, compared with control rats. Diabetes was confirmed in WBN/Kob rats after
      8 months in this study. The GBM width gradually thickened with age. The PEI
      anionic sites significantly decreased in the lamina rara externa (LRE) at 19
      months (vs. 2 and 10 months). The HS-GAG sites also significantly decreased in
      the LRE at 10 and 19 months (vs. 2 months). However, the CCG anionic sites and
      the CS-GAG sites significantly increased in the LRE and the lamina densa at 10
      months (vs. 2 months) and, after 19 months, returned to the level seen at 2
      months. Results indicate that there is an early transient increase in CS-GAG in
      the GBM while HS-GAG decreases. We noticed a transient increase in the CCG
      anionic sites at this early stage of diabetic glomerulosclerosis as well. The
      increase in CS-GAG may provide a marker for early diabetic changes in the GBM.

PMID- 9171303
TI  - Effects of endothelin 1 on phosphate transport in brush border membrane vesicles.
AB  - Endothelin is the most potent vasoconstrictive agent released from endothelial
      and many other types of cells. It has been reported that endothelin has
      physiological effects on the rat kidney, especially on the renal proximal
      tubules. We investigated the role of endothelin 1 in the renal brush border
      membrane. The V(max) of P(i) uptake by brush border membrane vesicles (BBMV) in
      the endothelin-1-treated group was significantly greater than that in the control
      group. There were no significant changes in apparent K(m) values between the two
      groups. To define the direct effect of endothelin 1 on P(i) transport of BBMV,
      BBMV from normal rats were incubated with endothelin 1 in vitro. The P(i) uptake
      by BBMV incubated with endothelin 1 did not differ from that by BBMV incubated
      with a salt solution as a control. These results suggested the probability of the
      presence of endothelin 1 receptor in the proximal tubules. Administration of the
      endothelin 1 might increase the P(i) reabsorption by BBMV according to changes in
      the capacity of the transporter.

PMID- 9171304
TI  - Effect of vitamin E on antioxidant enzymes, lipid peroxidation products and
      glomerulosclerosis in the rat remnant kidney.
AB  - In rats with five-sixth nephrectomy (remnant kidney), glomerulosclerosis was
      significantly reduced by dietary administration of vitamin E (alpha-tocopherol)
      during 11 and 16 weeks after reduction of nephron number. The activity of
      catalase and the production of H2O2 in remnant kidney cortex homogenate were not
      influenced by the vitamin E diet; however, the activities of glutathione
      peroxidase and superoxide dismutase were significantly increased (up to 140 and
      180%, respectively, after 16 weeks). Lipid peroxidation, evaluated by
      malonaldehyde and 4-hydroxynonenal concentrations, was decreased in cortex
      homogenates and in urine. Though the extent of the effect of vitamin E on
      antioxidant enzyme levels and lipid peroxidation is small, the important
      reduction of glomerulosclerosis is in favor of dietary supplementation with
      vitamin E.

PMID- 9171305
TI  - Roles of TGF-beta and latent TGF-beta-binding protein in glomerulosclerosis
      induced by two consecutive injections of monoclonal antibody 1-22-3 in rats.
AB  - The present study demonstrated the elevated synthesis and gene expressions of
      transforming growth factor beta (TGF-beta) or latent TGF-beta binding protein
      (LTBP) in an irreversible glomerulosclerosis rat model induced by two consecutive
      injections of monoclonal antibody (MoAb) 1-22-3. The rats were intravenously
      injected with 500 microg of MoAb 1-22-3 either once or twice at an interval of 2
      weeks. The rats were sacrificed at 24 h, 1 week, 2 weeks or 16 weeks after the
      last injection. At 24 h, the mesangiolytic changes in the rats with two
      injections of MoAb 1-22-3 were similar to those in the rats with one injection.
      The glomerular matrix score in the rats with two injections was significantly
      higher than that in the rats with one injection at weeks 1, 2 or 16. An increased
      LTBP localization in the glomeruli of the rats at week 1 after either one or two
      injections was detected in the segmentally expanded mesangial matrix. Moreover,
      LTBP in the glomeruli of rats at week 1 after two injections appeared to be more
      strongly stained in the enlarged mesangial matrix than that in the rats after one
      injection. A TGF-beta bioassay using mink lung epithelial cells revealed that the
      total TGF-beta in the glomerular culture conditioned medium in the rats at week 1
      after two injections was significantly larger than that in the rats after one
      injection. A Northern blotting analysis of the glomeruli showed that both the
      expressions of TGF-beta and LTBP mRNA in the rats after two injections were
      higher than those in the rats after one injection. These findings suggested that
      the elevated TGF-beta or LTBP may thus be related to the irreversible
      glomerulosclerosis that was induced by two injections of MoAb 1-22-3 into rats.

PMID- 9171306
TI  - Regulation of MHC class I expression by inflammatory cytokines in rat mesangial
      cells.
AB  - We investigated the regulation of major histocompatibility complex (MHC) class I
      expression by inflammatory cytokines and nitric oxide (NO) in rat mesangial cells
      by enzyme-linked immunosorbent assay and flow cytometry. MHC class I molecule
      expression on mesangial cells was significantly stimulated by interferon gamma,
      tumor necrosis factor alpha and interleukin 1beta, but not by interleukin 6, in a
      dose-dependent manner. Addition of SIN-1, an NO donor, did not affect the
      expression of cytokine-induced MHC class I expression. These results suggest that
      under inflammatory conditions mesangial cells may act as antigen-presenting cells
      in response to stimulation by cytokines and may be involved in the pathogenesis
      of immune-mediated glomerular disease.

PMID- 9171307
TI  - Structural changes in the renal proximal tubular cells induced by iodinated
      contrast media.
AB  - The renal morphologic changes induced by intravenously injected contrast media
      (CMs) were studied in 40 Wistar rats which had been deprived of water 24 h before
      the CM injection. In the first part of the investigation, the kidneys were fixed
      by perfusion for light and electron microscopy 2 h after injection of 3 g
      iodine/kg of iopamidol, iobitridol or iohexol. Control animals received
      physiologic saline. In the second part of the study, the fixation was performed
      48 h after the injection of the corresponding dose of iobitridol or iohexol. The
      structural changes were semiquantitatively evaluated by two independent observers
      unaware of the agent injected. The lysosomes of the proximal convoluted tubular
      cells showed moderate changes 2 h after the iopamidol injection. Iobitridol and
      iohexol induced prominent lysosomal alterations with signs of cytoplasmic injury.
      After 48 h, the changes induced by iobitridol had almost disappeared, whereas the
      iohexol group still showed a statistically significant vacuolization. Although
      the general physicochemical properties of iobitridol and iohexol appear similar
      in vitro, the different lysosomal alteration might reflect differences in their
      characteristics in vivo.

PMID- 9171308
TI  - Ontogenic expression of renal and hepatic angiotensin II receptor genes in the
      rat.
AB  - In addition to its well-characterized renal hemodynamic effects, angiotensin II
      (Ang II) promotes growth of cultured glomerular and tubular cells, suggesting a
      possible role in renal development. To better define potential developmental
      effects of Ang II, we examined the expression of Ang II receptors in embryonic
      (E19) and postnatal (1, 2, 3, 10 days, 6 weeks, 3 and 9 months) rat kidneys,
      using in situ autoradiography and the nonpeptide antagonists losartan and PD
      123177 to identify receptor subtypes. At E19, 125I-[Sar1, Ile8]Ang II binding was
      equally reduced by losartan and PD-123177, indicating the presence of both AT1
      and AT2 receptors. A progressive increase in Ang II receptor density occurred
      after birth, reaching a plateau at day 10. At that time, the AT1 subtype
      predominated and was virtually the sole subtype present thereafter. Ang II
      receptor density and AT1 mRNA levels decreased in aging rats. Total AT1 receptor
      mRNA levels in both kidney and liver were determined by Northern hybridization
      analysis using a radiolabeled AT1 anti-sense cRNA probe. In both tissues, AT1
      mRNA levels increased rapidly following birth, reached a maximum on day 10 and
      decreased thereafter. To further characterize the ontogenic effects on AT1 gene
      expression, renal AT1A and AT1B receptor mRNA isoforms were determined by reverse
      transcription and the polymerase chain reaction. No significant differences were
      observed during maturation between the relative levels of AT1A and AT1B mRNAs,
      with the AT1A isoform accounting for approximately 78% at any time point. Thus,
      renal AT1 receptor density increases rapidly after birth, in association with an
      increase in both AT1A and AT1B receptor gene expression. As the predominant
      receptor isoform in the adult kidney, the AT1A receptor may account for the
      majority of the effects of Ang II on glomerular and tubular function.

PMID- 9171309
TI  - Syndrome of inappropriate antidiuresis without involving inappropriate secretion
      of vasopressin in an elderly woman: effect of intravenous administration of the
      nonpeptide vasopressin V2 receptor antagonist OPC-31260.
AB  - We describe a 78-year-old female patient with severe hyponatremia owing to
      inappropriate antidiuresis. Despite hyponatremia, the urinary sodium excretion
      persisted with urine osmolality exceeding plasma osmolality. Although a water
      load decreased plasma sodium concentration and osmolality, the patient excreted
      only 40% of the water load after 4 h without decreased urine sodium
      concentrations and osmolality. The plasma vasopressin levels relative to plasma
      osmolality were not inappropriately elevated. Intravenous administration of the
      selective nonpeptide vasopressin V2 antagonist OPC-31260 decreased sodium
      concentration and osmolality in urine to lower values than in plasma.
      Concomitantly, the urine volume excretion increased markedly. In addition,
      restriction of water or administration of demeclocycline improved plasma sodium
      and plasma vasopressin levels relative to plasma osmolality to be normal. The
      findings indicate that the inappropriate antidiuresis in this patient was related
      to hyperfunction of the arginine vasopressin V2 receptor in the kidney which is
      not due to inappropriately secreted vasopressin.

PMID- 9171310
TI  - Increased risk of cardiovascular disease with erythropoietin in chronic dialysis
      patients.

PMID- 9171311
TI  - Tuberculous peritonitis in continuous ambulatory peritoneal dialysis.

PMID- 9171312
TI  - Red cell folate: an appropriate index of folate body stores.

PMID- 9171313
TI  - Folic acid supplementation improves erythropoietin response.

PMID- 9171314
TI  - Nitric oxide and the paradox of ischemic acute renal failure-again.

PMID- 9171315
TI  - Fatal cerebral air embolism in a renal transplant recipient.

PMID- 9171316
TI  - Low-molecular-weight heparin and lipoprotein(a) in patients with chronic renal
      failure.

PMID- 9171317
TI  - Electrophysiological evidence for agonist properties of flumazenil, a
      benzodiazepine receptor antagonist, in rat hippocampus slices.
AB  - The purpose of this study was to determine the ability of the putative
      benzodiazepine antagonist flumazenil to modulate the excitatory synaptic
      responses recorded from rat hippocampus slices. The benzodiazepine agonist
      clonazepam was demonstrated to depress the CA1 population spike. This effect was
      attributed to an enhancement of GABA efficacy after its electrically-elicited
      release from local inhibitory circuitry. As an unexpected effect, flumazenil
      failed to antagonize this depressing effect. Moreover, flumazemil was observed to
      significantly depress, on its own, the magnitude of the evoked response to the
      activation of the excitatory afferents. This intrinsic depressant activity of
      flumazenil suggests that flumazenil acts 'in vitro' as an agonist at the
      benzodiazepine receptors, and is consistent with some previously reported
      atypical effects of flumazenil 'in vivo'.

PMID- 9171318
TI  - Pathogenesis of the neurotoxicity caused by anti-GD2 antibody therapy.
AB  - After treatment of melanomas with anti-GD2 monoclonal antibody (MAb) (14G2a),
      some patients develop sensorimotor demyelinating polyneuropathy with and without
      the syndrome of inappropriate antidiuretic hormone (SIADH). To clarify what
      causes the neurotoxicity of anti-GD2 MAb, we investigated the immunohistochemical
      localization of GD2 in the human nervous system. Anti-GD2 MAb (14G2a) reacted
      with the myelin sheaths in the peripheral nerves as well as with the pituicyte
      cytoplasm in the posterior lobe of the pituitary gland. We assume that the
      binding of anti-GD2 MAb to peripheral nerve myelin and the pituicytes in the
      posterior pituitary causes sensorimotor demyelinating neuropathy and SIADH.

PMID- 9171320
TI  - Nonlinear dynamics and multiple sclerosis.

PMID- 9171319
TI  - Autonomic involvement in Wilson's disease: a study of sympathetic skin response
      and RR interval variation.
AB  - Autonomic nervous system involvement in Wilson's disease (WD) was studied in 25
      patients by sympathetic skin response (SSR) and RR interval variation (RRIV). The
      control group consisted of age-matched healthy subjects. Palmar SSRs were
      obtained by central activation from median nerve stimulation and by activation of
      sympathetic trunk from magnetic stimulation of the neck. Electric SSRs were
      prolonged in 11 patients and absent in 2; magnetic SSRs were delayed in 4 and
      absent in 1; and the sympathetic central conduction time was prolonged in 3. The
      mean latencies and mean central conduction of the SSRs were all significantly
      prolonged in WD when compared to the control group. On the other hand,
      parasympathetic function was abnormal in 3 patients only during forced deep
      breathing, and as a group only mean D% was significantly reduced. The present
      findings suggest that autonomic dysfunction may occur in WD, and that sympathetic
      function is predominantly affected, mainly due to central involvement.

PMID- 9171321
TI  - In vitro virus propagation and high cellular responsiveness to the infected cells
      in patients with HTLV-I-associated myelopathy (HAM/TSP).
AB  - The reasons for the development of HTLV-I-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) in certain infected individuals remain poorly understood,
      but the susceptibility should involve both viral factors and host conditions. To
      assess simultaneously both virus-induced activation of infected cells and the
      cellular response to virus producing cells, an analysis of fractionated
      peripheral blood lymphocytes obtained from patients with HAM/TSP (n = 15) were
      compared with those of asymptomatic HTLV-I carriers (n = 9) in an age-matched
      manner. The in vitro propagation of HTLV-I infection was evaluated as the
      spontaneous thymidine incorporation into CD4+ cells, and proliferative response
      of CD8+ cells against cultured and irradiated autologous CD4+ cells was employed
      to analyze the HTLV-I-induced cellular response. The comparative analysis using
      these two parameters demonstrated that HAM/TSP patients were characterized by the
      concomitance of a high inducibility of HTLV-I propagation and a high cellular
      responsiveness against HTLV-I as compared with asymptomatic HTLV-I carriers,
      suggesting the involvement of both of these factors in disease susceptibility. In
      addition, the coupled evaluation of these two in vitro phenomena may offer a
      better diagnostic hallmark for HTLV-I seropositive myelopathy cases with other
      known cause of myelopathy.

PMID- 9171322
TI  - Palpebral ptosis and muscle fatiguability associated with perineurial cell
      ensheathment of muscle fibers: a new disease of the neuromuscular junction?
AB  - Perineurial cell ensheathment of muscle fibers has been reported only in one
      patient. Here we describe a new case with identical morphologic features and a
      similar, but milder clinical course characterized by progressive muscle weakness
      and bilateral palpebral ptosis. EMG examination (including repetitive
      stimulation) and antibodies against acetylcholine receptors were normal. Muscle
      biopsy revealed several muscle fibers encircled by stratified rings of
      homogeneous material in which elongated nuclei were visible; this material was
      positively stained by antibodies directed at epithelial membrane antigen. On
      ultrastructural examination these encircling-fiber spirals had the
      characteristics of perineurial cells. It is not clear yet whether perineurial
      cell ensheathment of muscle fibers is an occasional feature, or whether it has a
      pathogenetic role in the clinical picture of both cases. The perineurial sheaths
      might alter the correct neuromuscular transmission mimicking a myasthenia-like
      disease, either by interfering with the neuromuscular junction, or by changing
      the microenvironment, and, thus, altering the general excitability of the muscle
      fibers.

PMID- 9171323
TI  - Histological determination of nitric oxide synthase (NOS) and NADPH-diaphorase in
      ragged-red fibers from patients with mitochondrial encephalomyopathies.
AB  - To determine localization of nitric oxide synthase in diseased muscle, we
      performed immunohistochemical analyses of neuronal-type nitric oxide synthase
      (nNOS) and endothelial-type nitric oxide synthase (ec-NOS) in biopsied muscles
      from five patients with mitochondrial encephalomyopathies. Immunostaining of nNOS
      was prominent in the sarcolemmal region of the ragged-red fibers, and weak in the
      sarcolemmal region of normal fibers. Immunostaining of ec-NOS was strongly
      positive in the myofibrils of ragged-red fibers. Ec-NOS immunoreactivity
      corresponded to fibers positive for SDH by histochemistry. Histochemical methods
      revealed prominent staining for NADPH-diaphorase on surface membranes of the
      ragged-red fibers. Findings suggest that nitric oxide is important in the muscles
      of patients with mitochondrial encephalomyopathies.

PMID- 9171324
TI  - Variable histomorphology of muscle in congenital muscular dystrophy.
AB  - Congenital muscular dystrophy (CMD) is a relatively uncommon disease with a
      controversial nosological status. That collagen synthesis could be the primary
      abnormality has been suggested earlier (Fidzianska et al., 1982). Amongst
      eighteen cases of CMD diagnosed during the past twelve years, muscle biopsy in
      three cases revealed prominence of myofibre necrosis and phagocytosis, and serum
      CPK was markedly elevated suggesting a rapidly progressive form. In twelve cases,
      marked increase in endomysial collagen, pronounced fallout of myofibres and
      significant fibre diameter variation was seen. This was associated with
      myonecrosis and regenerative activity of mild degree resembling the classical
      form of CMD. In the remaining three cases, polyfocal, polyphasic necrosis was
      noticed. Fibre splitting was more frequently observed, better delineated in the
      enzyme histochemical preparations, affecting both fibre types, while endomysial
      fibrofatty tissue was only moderately increased. The histomorphology in the
      latter group resembled that of limb girdle dystrophy. Ultrastructural findings in
      all the eighteen cases correlated well with light microscopic observations.
      lmmunohistochemical studies done on three of the eighteen cases showed normal
      localization of dystrophin protein. Such variable histomorphology, revealing a
      spectrum of myopathic features, suggests that the primary change in CMD is likely
      to be in the myofibre rather than in collagen synthesis.

PMID- 9171325
TI  - Hippocampal pathology in diffuse Lewy body disease using ubiquitin
      immunohistochemistry.
AB  - Various ubiquitin-positive structures in the hippocampus in diffuse Lewy body
      disease (n=12) and non-demented aged subjects (n=3) were investigated
      immunohistochemically. These structures were composed of ubiquitin-positive
      granular structures (UPG), ubiquitin-positive neuritic structures (UPN),
      spheroidal structures, neuritic plaques, neurofibrillary tangles (NFT), Lewy
      bodies (LB) and ubiquitin-positive neurons. UPG, UPN, spheroidal structures and
      neuritic plaques were distributed with special reference to the hippocampal
      pathway assumed in this study. This pathway was thought to run along the stratum
      oriens, mostly perforating the stratum pyramidale at many sites of the subiculum
      and CA1-3, and to end partly in the CA2-3 and the subiculum of the uncus (UPG or
      UPN). After perforating the stratum pyramidale and giving off terminal branches
      (ubiquitin-positive neurons or neuritic plaques with degenerative neurites), it
      was thought to run along the stratum radiatum and continue along the stratum
      moleculare of the dentate gyrus, forming synapses with the apical dendrites from
      the stratum pyramidale and the stratum granulosum (spheroidal structures or
      neuritic plaques). These findings suggest that many of the ubiquitin-positive
      structures may be caused by degeneration of terminal or distal axons of this
      pathway. NFT and LB also had a somewhat orderly distribution with reference to
      this pathway.

PMID- 9171326
TI  - Assessment of cerebrovascular reactivity by dynamic susceptibility contrast
      enhanced MR imaging.
AB  - In patients with cerebrovascular disease the acetazolamide (ACZ) test is
      performed to evaluate the decrease in cerebral perfusion pressure (CPP) through
      the investigation of the vasomotor reactivity (VMR). This latter is currently
      assessed with ACZ with several methods. Recently, magnetic resonance imaging
      (MRI) techniques have been developed that are sensitive to stimulus-induced
      changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient
      echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed
      to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic
      parameters rCBV, MTT, and rCBF were evaluated at baseline after the first
      injection of gadopentetate dimeglumine and 10 min after the intravenous
      administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of
      hemodynamic parameters was performed over the whole hemisphere and also within
      regions of interest. The significances of the mean differences, before and after
      ACZ, were assessed with repeated-measures ANOVA with two within factors:
      laterality (right-left) and ACZ. DSC-MRI with ACZ test was performed in ten
      healthy controls (aged 51.4+/-16.2 years). The cerebral hemispheric ratio for the
      three parameters (cerebral blood volume (CBV), mean transit time (MTT), and
      cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to
      white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively.
      As the laterality effect was not significant, left and right hemispheric values
      were averaged. A significant increase of all hemodynamic parameters was observed
      after ACZ (P<0.01-0.001). The same changes for CBV, CBF and MTT were observed
      after ACZ according to the regions of interest (P<0.006-0.015). DSC-MRI is a non
      invasive method which enables the assessment of VMR. This technique may be added
      to any conventional MRI in order to detect a hemodynamic impact of an ICA
      stenosis. Therefore, it might be useful in determining the appropriate management
      when the indication for surgical versus medical therapy is in question.

PMID- 9171327
TI  - Cerebellar pathology in sporadic and familial Alzheimer's disease including APP
      717 (Val-->Ile) mutation cases: a morphometric investigation.
AB  - Familial Alzheimer's disease (FAD) tends to present with more prominent
      neurological symptoms including cerebellar signs than sporadic Alzheimer's
      disease (SAD). In order to elucidate the pathological differences in the
      cerebellum, which may be associated with the cerebellar symptoms, we have
      investigated morphometrically beta-amyloid deposits, atrocytosis, Purkinje cells
      and dentate neurons in the cerebellum of 10 FAD patients including two cases with
      the beta-amyloid precursor protein (APP) gene mutation (APP717 Val-->Ile), 10 SAD
      patients and 10 non-demented age-matched controls. The regions examined included
      the molecular, Purkinje cell and granular cell layers, the cerebellar white
      matter and the dentate nucleus. Purkinje cell density in FAD was significantly
      lower than in SAD. There were no significant differences in the density of
      dentate neurons among the three groups. The density of astrocytes in FAD was
      significantly greater than that in SAD in the granular cell and Purkinje cell
      layers and in the white matter. There were no significant differences in the
      amount and subtypes of beta-amyloid deposits (extracellular, vascular and
      perivascular) between FAD and SAD in all the regions investigated. In two cases
      with the APP mutation, both Purkinje cell loss and beta-amyloid deposition in the
      cerebellum were greater than the mean for FAD and SAD cases. Astrocytosis in the
      mutation cases was not greater than the mean for FAD cases except for the dentate
      nucleus in one case. Extracellular beta-amyloid deposits were not seen in any of
      the control cases although amyloid angiopathy was observed in one case. This
      study demonstrates for the first time that Purkinje cell loss and reactive
      astrocytosis of the cerebellum in FAD are more severe than in SAD, but that beta
      amyloid deposition in the cerebellum in both FAD and SAD are similar. The more
      prominent neurological signs observed in FAD may be explained by more severe
      neurodegeneration than are found in sporadic cases.

PMID- 9171328
TI  - Food embolus.
AB  - A 74 year old man with chronic dysphagia acutely developed nausea, vomiting and
      fever, followed by abrupt, fatal brainstem stroke. Autopsy revealed an
      esophagoatrial fistula with multiple food emboli to visceral and cerebral
      arteries. Review of previous cases indicates that new onset atrial fibrillation
      or pericardial effusion in patients with chronic esophageal symptoms may herald
      fistula formation. Early recognition of such fistulas may provide an opportunity
      to intervene before catastrophic embolization or gastrointestinal hemorrhaging
      occurs.

PMID- 9171329
TI  - Incidental cerebral venous thrombosis in a patient with multiple sclerosis.
AB  - Cerebral venous thrombosis (CVT) is rarely reported in patients with multiple
      sclerosis. We recently managed a 32 year-old Saudi female patient who was managed
      for a relapse of her multiple sclerosis but in whom CVT was incidentally found in
      the course of investigations. She was asymptomatic with regards to the CVT and
      she had no identifiable predisposing factor apart from her recent confinement
      which was uneventful. The case underscores the importance of looking for other
      lesions that may be 'clinically silent' in MS patients presenting with relapse as
      well as emphasising the advantage of neuroimaging in revealing unsuspected but
      potentially fatal disorders.

PMID- 9171330
TI  - Contralateral abolition of essential tremor following a pontine stroke.
AB  - A 90-year-old man with a longstanding bilateral essential tremor presented with
      right-sided weakness of sudden onset. The CT scan of the brain showed a hypodense
      area in the left side of the pons consistent with an infarction. The paralysis
      disappeared without recurrence of the tremor on the right, but the tremor
      persisted on the left. It is likely that the fronto-rubro-spinal pathway had been
      interrupted at the level of the pons abolishing the tremor on the right side.

PMID- 9171331
TI  - MR findings of Creutzfeldt-Jakob disease.

PMID- 9171332
TI  - Function of the Greek key connection analysed using circular permutants of
      superoxide dismutase.
AB  - Human Cu,Zn superoxide dismutase (SOD) is a single domain all beta-sheet protein
      with its eight beta-strands arranged as a Greek key beta-barrel or immunoglobulin
      fold. Three circularly permuted variants of SOD were made by joining the native
      amino- and carboxy-termini, and introducing new termini at sites originally
      within connections between beta-strands. The locations of the new termini were
      chosen to interrupt beta-turns between the two N-terminal beta-hairpins and the
      short cross-barrel Greek key connection. Expression levels in the Escherichia
      coli periplasm were indistinguishable from that of native SOD. Reaction rates for
      the purified proteins were similar to those of the native enzyme, indicating that
      the permutants are correctly folded. Interrupting the covalent cross-bracing
      provided by the Greek key connection reduced the stability of the protein by
      approximately 1.0 kcal/mol, indicating only a slight contribution to
      conformational stability. The experiments test and eliminate two hypotheses for
      folding pathways for Greek key beta-barrels that require N-terminal beta-hairpins
      or covalent attachment across the short Greek key connection.

PMID- 9171333
TI  - The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase
      encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox
      regulation.
AB  - The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent
      glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae.
      Previous studies showed that GPD1 plays a role in osmoadaptation since its
      expression is induced by osmotic stress and gpd1 delta mutants are osmosensitive.
      Here we report that GPD2 has an entirely different physiological role. Expression
      of GPD2 is not affected by changes in external osmolarity, but is stimulated by
      anoxic conditions. Mutants lacking GPD2 show poor growth under anaerobic
      conditions. Mutants deleted for both GPD1 and GPD2 do not produce detectable
      glycerol, are highly osmosensitive and fail to grow under anoxic conditions. This
      growth inhibition, which is accompanied by a strong intracellular accumulation of
      NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of
      NADH. Thus, glycerol formation is strictly required as a redox sink for excess
      cytosolic NADH during anaerobic metabolism. The anaerobic induction of GPD2 is
      independent of the HOG pathway which controls the osmotic induction of GPD1.
      Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative
      regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is
      induced under aerobic conditions by the addition of bisulfite which causes NADH
      accumulation by inhibiting the final, reductive step in ethanol fermentation and
      this induction is reversed by addition of acetaldehyde. We conclude that
      expression of GPD2 is controlled by a novel, oxygen-independent, signalling
      pathway which is required to regulate metabolism under anoxic conditions.

PMID- 9171334
TI  - The protease-protected 30 kDa domain of SecA is largely inaccessible to the
      membrane lipid phase.
AB  - SecA binds to the inner membrane of Escherichia coli through low affinity lipid
      interactions or with high affinity at SecYEG, the integral domain of preprotein
      translocase. Upon addition of preprotein and nucleotide, a 30 kDa domain of
      SecYEG-bound SecA is protected from proteolysis via membrane insertion. Such
      protection could result from some combination of insertion into the lipid phase,
      into a proteinaceous environment or across the membrane. To assess the exposure
      of SecYEG-bound SecA to membrane lipids, a radiolabeled, photoactivatable and
      lipid-partitioning crosslinker, 3-trifluoromethyl-3-(m[125I]iodophenyl) diazirine
      benzoic acid ester, was incorporated into inner membrane vesicles. The 30 kDa
      domain of SecYEG-bound SecA, inserted into the membrane in response to
      translocation ligands, is 18-fold less labeled than SecY, which is labeled
      effectively. In contrast, incorporation of the purified 30 kDa SecA fragment into
      crosslinker-containing detergent micelles or addition of detergent to crosslinker
      containing membranes bearing the protease-protected SecA domain readily allows
      for labeling of this domain. We propose that the protease-inaccessible 30 kDa
      SecA domain is shielded from the fatty acyl membrane phase by membrane-spanning
      SecYEG helices and/or is largely exposed to the periplasm.

PMID- 9171335
TI  - Negatively charged amino acid residues play an active role in orienting the Sec
      independent Pf3 coat protein in the Escherichia coli inner membrane.
AB  - The coat protein of Pseudomonas aeruginosa phage Pf3 is transiently inserted into
      the bacterial inner membrane with a single transmembrane anchor sequence in the
      N(out)C(in) orientation. The N-terminal sequence immediately flanking the
      membrane anchor contains one negatively charged residue, whereas the C-terminal
      hydrophilic segment has two positively charged residues. To investigate how the
      orientation of this protein is achieved, the three flanking charged amino acid
      residues were altered. Membrane insertion was analyzed in vivo using the
      accessibility to externally added protease and in vitro by testing the insertion
      into inverted Escherichia coli membrane vesicles. In both systems, the
      orientation of the protein was completely reversed for the oppositely charged
      mutant coat protein (RD mutant). In addition, we show in vivo that the
      electrochemical membrane potential is necessary for the translocation of both the
      wild-type and the mutant Pf3 coat proteins, suggesting that membrane insertion is
      driven by electrophoretic forces.

PMID- 9171336
TI  - Multiple interactions of components mediating preprotein translocation across the
      inner mitochondrial membrane.
AB  - The protein transport machinery of the inner mitochondrial membrane contains
      three essential Tim proteins. Tim17 and Tim23 are thought to build a preprotein
      translocation channel, while Tim44 transiently interacts with the matrix heat
      shock protein Hsp70 to form an ATP-driven import motor. For this report we
      characterized the biogenesis and interactions of Tim proteins. (i) Import of the
      precursor of Tim44 into the inner membrane requires mtHsp70, whereas import and
      inner membrane integration of the precursors of Tim17 and Tim23 are independent
      of functional mtHsp70. (ii) Tim17 efficiently associates with Tim23 and mtHsp70,
      but only weakly with Tim44. (iii) Depletion of Tim44 does not affect the co
      precipitation of Tim17 with antibodies directed against mtHsp70. (iv) Tim23
      associates with both Tim44 and Tim17, suggesting the presence of two Tim23 pools
      in the inner membrane, a Tim44-Tim23-containing sub-complex and a Tim23-Tim17
      containing sub-complex. (v) The association of mtHsp70 with the Tim23-Tim17 sub
      complex is ATP sensitive and can be distinguished from the mtHsp70-Tim44
      interaction by the differential influence of an amino acid substitution in
      mtHsp70. (vi) Genetic evidence, suppression of the protein import defect of a
      tim17 yeast mutant by overexpression of mtHsp70 and synthetic lethality of
      conditional mutants in the genes of Tim17 and mtHsp70, supports a functional
      interaction of mtHsp70 with Tim17. We conclude that the protein transport
      machinery of the mitochondrial inner membrane consists of dynamically interacting
      sub-complexes, each of which transiently binds mtHsp70.

PMID- 9171337
TI  - Insertion into the mitochondrial inner membrane of a polytopic protein, the
      nuclear-encoded Oxa1p.
AB  - Oxa1p, a nuclear-encoded protein of the mitochondrial inner membrane with five
      predicted transmembrane (TM) segments is synthesized as a precursor (pOxa1p) with
      an N-terminal presequence. It becomes imported in a process requiring the
      membrane potential, matrix ATP, mt-Hsp70 and the mitochondrial processing
      peptidase (MPP). After processing, the negatively charged N-terminus of Oxa1p
      (approximately 90 amino acid residues) is translocated back across the inner
      membrane into the intermembrane space and thereby attains its native N(out)-C(in)
      orientation. This export event is dependent on the membrane potential. Chimeric
      preproteins containing N-terminal stretches of increasing lengths of Oxa1p fused
      on mouse dehydrofolate reductase (DHFR) were imported into isolated mitochondria.
      In each case, their DHFR moieties crossed the inner membrane into the matrix.
      Thus Oxa1p apparently does not contain a stop transfer signal. Instead the TM
      segments are inserted into the membrane from the matrix side in a pairwise
      fashion. The sorting pathway of pOxa1p is suggested to combine the pathways of
      general import into the matrix with a bacterial-type export process. We postulate
      that at least two different sorting pathways exist in mitochondria for polytopic
      inner membrane proteins, the evolutionarily novel pathway for members of the
      ADP/ATP carrier family and a conserved Oxa1p-type pathway.

PMID- 9171338
TI  - A novel structural model for regulation of clathrin function.
AB  - The distinctive triskelion shape of clathrin allows assembly into polyhedral
      lattices during the process of clathrin-coated vesicle formation. We have used
      random and site-directed mutagenesis of the yeast clathrin heavy chain gene
      (CHC1) to characterize regions which determine Chc trimerization and binding to
      the clathrin light chain (Clc) subunit. Analysis of the mutants indicates that
      mutations in the trimerization domain at the triskelion vertex, as well as
      mutations in the adjacent leg domain, frequently influence Clc binding.
      Strikingly, one mutation in the trimerization domain enhances the association of
      Clc with Chc. Additional mutations in the trimerization domain, in combination
      with mutations in the adjacent leg domain, exhibit severe defects in Clc binding
      while maintaining near normal trimerization properties. The position of these
      trimerization domain mutations on one face of a putative alpha-helix defines a
      region on the trimer surface that interacts directly with Clc. These results
      suggest that Clc extends into the Chc trimerization domain from the adjacent leg,
      thereby bridging the two domains. On the basis of this conclusion, we propose a
      new model for the organization of the triskelion vertex which provides a
      structural basis for regulatory effects of Clc on clathrin function.

PMID- 9171339
TI  - Regulatory interactions in the recognition of endocytic sorting signals by AP-2
      complexes.
AB  - Many plasma membrane proteins destined for endocytosis are concentrated into
      clathrin-coated pits through the recognition of a tyrosine-based motif in their
      cytosolic domains by an adaptor (AP-2) complex. The mu2 subunit of isolated AP-2
      complexes binds specifically, but rather weakly, to proteins bearing the tyrosine
      based signal. We now demonstrate, using peptides with a photoreactive probe, that
      this binding is strengthened significantly when the AP-2 complex is present in
      clathrin coats, indicating that there is cooperativity between receptor-AP-2
      interactions and coat formation. Phosphoinositides with a phosphate at the D-3
      position of the inositol ring, but not other isomers, also increase the affinity
      of the AP-2 complex for the tyrosine-based motif. AP-2 is the first protein known
      (in any context) to interact with phosphatidylinositol 3-phosphate. Our findings
      indicate that receptor recruitment can be coupled to clathrin coat assembly and
      suggest a mechanism for regulation of membrane traffic by lipid products of
      phosphoinositide 3-kinases.

PMID- 9171340
TI  - The linker region of the ABC-transporter Ste6 mediates ubiquitination and fast
      turnover of the protein.
AB  - Upon block of endocytosis, the a-factor transporter Ste6 accumulates in a
      ubiquitinated form at the plasma membrane. Here we show that the linker region,
      which connects the two homologous halves of Ste6, contains a signal which
      mediates ubiquitination and fast turnover of Ste6. This signal was also
      functional in the context of another plasma membrane protein. Deletion of an
      acidic stretch in the linker region ('A-box') strongly stabilized Ste6. The A-box
      contains a sequence motif ('DAKTI') which resembles the putative endocytosis
      signal of the alpha-factor receptor Ste2 ('DAKSS'). Deletion of the DAKTI
      sequence also stabilized Ste6 but, however, not as strongly as the A-box
      deletion. There was a correlation between the half-life of the mutants and the
      degree of ubiquitination: while ubiquitination of the deltaDAKTI mutant was
      reduced compared with wild-type Ste6, no ubiquitination could be detected for the
      more stable deltaA-box variant. Loss of ubiquitination seemed to affect Ste6
      trafficking. In contrast to wild-type Ste6, which was associated mainly with
      internal membranes, the ubiquitination-deficient mutants accumulated at the
      plasma membrane, as demonstrated by immunofluorescence and cell fractionation
      experiments. These findings suggest that ubiquitination is required for efficient
      endocytosis of Ste6 from the plasma membrane.

PMID- 9171341
TI  - An early and massive wave of germinal cell apoptosis is required for the
      development of functional spermatogenesis.
AB  - Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male
      germinal cells show a highly abnormal adult spermatogenesis accompanied by
      sterility. This appears to result from the prevention of an early and massive
      wave of apoptosis in the testis, which occurs among germinal cells during the
      first round of spermatogenesis. In contrast, sporadic apoptosis among
      spermatogonia, which occurs in normal adult testis, is not prevented in adult
      transgenic mice. The physiological early apoptotic wave in the testis is
      coincident, in timing and localization, with a temporary high expression of the
      apoptosis-promoting protein Bax, which disappears at sexual maturity. The
      critical role played by the intracellular balance, probably hormonally
      controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in
      normal mouse testis) in this early apoptotic wave is shown by the occurrence of a
      comparable testicular syndrome in mice defective in the bax gene. The apoptotic
      wave appears necessary for normal mature spermatogenesis to develop, probably
      because it maintains a critical cell number ratio between some germinal cell
      stages and Sertoli cells, whose normal functions and differentiation involve an
      elaborate network of communication.

PMID- 9171342
TI  - Multiple species of CPP32 and Mch2 are the major active caspases present in
      apoptotic cells.
AB  - The activity of ICE-like proteases or caspases is essential for apoptosis.
      Multiple caspases participate in apoptosis in mammalian cells but how many
      caspases are involved and what is their relative contribution to cell death is
      poorly understood. To identify caspases activated in apoptotic cells, we
      developed an approach to simultaneously detect multiple active caspases. Using
      tumor cells as a model, we have found that CPP32 (caspase 3) and Mch2 (caspase 6)
      are the major active caspases in apoptotic cells, and are activated in response
      to distinct apoptosis-inducing stimuli and in all cell lines analyzed. Both CPP32
      and Mch2 are present in apoptotic cells as multiple active species. In a given
      cell line these species remained the same irrespective of the apoptotic stimulus
      used. However, the species of CPP32 and Mch2 detected varied between cell lines,
      indicating differences in caspase processing. The strategy described here is
      widely applicable to identify active caspases involved in apoptosis.

PMID- 9171343
TI  - T-cell receptor ligation by peptide/MHC induces activation of a caspase in
      immature thymocytes: the molecular basis of negative selection.
AB  - T-cell receptors (TCRs) are created by a stochastic gene rearrangement process
      during thymocyte development, generating thymocytes bearing useful, as well as
      unwanted, specificities. Within the latter group, autoreactive thymocytes arise
      which are subsequently eliminated via a thymocyte-specific apoptotic mechanism,
      termed negative selection. The molecular basis of this deletion is unknown. Here,
      we show that TCR triggering by peptide/MHC ligands activates a caspase in double
      positive (DP) CD4+ CD8+ thymocytes, resulting in their death. Inhibition of this
      enzymatic activity prevents antigen-induced death of DP thymocytes in fetal
      thymic organ culture (FTOC) from TCR transgenic mice as well as apoptosis induced
      by anti-CD3epsilon monoclonal antibody and corticosteroids in FTOC of normal
      C57BL/6 mice. Hence, a common caspase mediates immature thymocyte susceptibility
      to cell death.

PMID- 9171345
TI  - The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas
      and FAK, and the associated accumulation of these proteins in peripheral focal
      adhesions.
AB  - Pathogenic Yersinia resist uptake by eukaryotic cells by a mechanism involving
      the virulence protein YopH, a protein tyrosine phosphatase. We show that p130Cas
      and FAK are phosphorylated and recruited to peripheral focal complexes during
      bacterial uptake in HeLa cells. The inactive form of YopH interacts with the
      tyrosine phosphorylated forms of FAK and p130Cas and co-localizes with these
      proteins in focal adhesions. On the other hand, the presence of active YopH
      results in inhibition of uptake, dephosphorylation of p130Cas and FAK, and
      disruption of peripheral focal complexes. We suggest that p130Cas and FAK are
      substrates for YopH and that the dephosphorylation of these proteins impairs the
      uptake of Yersinia pseudotuberculosis into HeLa cells.

PMID- 9171344
TI  - Adenovirus type 5 fiber knob binds to MHC class I alpha2 domain at the surface of
      human epithelial and B lymphoblastoid cells.
AB  - Adenovirus serotype 5 (Ad5) fiber receptor was investigated using reverse
      antibody biopanning of a phage-displayed hexapeptide library, and virus
      neutralizing monoclonal antibodies (mAbs 1D6.3 and 7A2.7) raised against
      recombinant Ad5 fiber knob. Both mAbs inhibited attachment of Ad5 to HeLa cells.
      Mimotopes of 1D6.3 showed homology with the C-terminal segment of the alpha2
      domain of the heavy chain of human MHC class I molecules (MHC-I alpha2), and
      mimotopes of 7A2.7 were consensus to human fibronectin type III (FNIII) modules.
      In vitro, GST-fused MHC-I alpha2- and FNIII-derived oligopeptides interacted with
      recombinant fibers in a subgroup-specific manner. In vivo, the MHC-I alpha2
      synthetic icosapeptide RAIVGFRVQWLRRYFVNGSR showed a net neutralization effect on
      Ad5 in HeLa cells, whereas the FNIII icosapeptide RHILWTPANTPAMGYLARVS
      significantly increased Ad5 binding to HeLa cells. Daudi cells, which lack
      surface expression of HLA class I molecules, showed a weak capacity for Ad5
      binding. In beta2-microglobulin-transfected Daudi cells, Ad5 attachment and
      permissivity were restored to HeLa cell levels, with 4000 receptors per cell and
      a binding constant of 1.4x10(10)/M. The results suggested that the conserved
      region of MHC-I alpha2-domain including Trp167 represents a high affinity
      receptor for Ad5 fiber knob, whereas ubiquitous FNIII modules would serve as
      auxiliary receptors.

PMID- 9171346
TI  - Control of type IV collagenase activity by components of the urokinase-plasmin
      system: a regulatory mechanism with cell-bound reactants.
AB  - The urokinase-type plasminogen activator (uPA) and the matrix-degrading
      metalloproteinases MMP-2 and MMP-9 (type IV collagenases/gelatinases) have been
      implicated in a variety of invasive processes, including tumor invasion,
      metastasis and angiogenesis. MMP-2 and MMP-9 are secreted in the form of inactive
      zymogens that are activated extracellularly, a fundamental process for the
      control of their activity. The physiological mechanism(s) of gelatinase
      activation are still poorly understood; their comprehension may provide tools to
      control cell invasion. The data reported in this paper show multiple roles of the
      uPA-plasmin system in the control of gelatinase activity: (i) both gelatinases
      are associated with the cell surface; binding of uPA and plasmin(ogen) to the
      cell surface results in gelatinase activation without the action of other metallo
      or acid proteinases; (ii) inhibition of uPA or plasminogen binding to the cell
      surface blocks gelatinase activation; (iii) in soluble phase plasmin degrades
      both gelatinases; and (iv) gelatinase activation and degradation occur in a dose-
      and time-dependent manner in the presence of physiological plasminogen and uPA
      concentrations. Thus, the uPA-plasmin system may represent a physiological
      mechanism for the control of gelatinase activity.

PMID- 9171347
TI  - The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for
      activation of mouse platelets by collagen.
AB  - Activation of mouse platelets by collagen is associated with tyrosine
      phosphorylation of multiple proteins including the Fc receptor gamma-chain, the
      tyrosine kinase Syk and phospholipase Cgamma2, suggesting that collagen signals
      in a manner similar to that of immune receptors. This hypothesis has been tested
      using platelets from mice lacking the Fc receptor gamma-chain or Syk. Tyrosine
      phosphorylation of Syk and phospholipase Cgamma2 by collagen stimulation is
      absent in mice lacking the Fc receptor gamma-chain. Tyrosine phosphorylation of
      phospholipase Cgamma2 by collagen stimulation is also absent in mice platelets
      which lack Syk, although phosphorylation of the Fc receptor gamma-chain is
      maintained. In contrast, tyrosine phosphorylation of platelet proteins by the G
      protein-coupled receptor agonist thrombin is maintained in mouse platelets
      deficient in Fc receptor gamma-chain or Syk. The absence of Fc receptor gamma
      chain or Syk is accompanied by a loss of secretion and aggregation responses in
      collagen- but not thrombin-stimulated platelets. These observations provide the
      first direct evidence of an essential role for the immunoreceptor tyrosine-based
      activation motif (ITAM) in signalling by a non-immune receptor stimulus.

PMID- 9171348
TI  - Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36
      anchored Lyn tyrosine kinase in thrombin-stimulated platelets.
AB  - Chk/Hyl is a recently isolated non-receptor tyrosine kinase with greatest
      homology to a ubiquitous negative regulator of Src family kinases, Csk. To
      understand the significance of co-expression of Chk and Csk in platelets, we
      examined the subcellular localization of each protein. Chk, but not Csk, was
      completely translocated from the Triton X-100-soluble to the Triton X-100
      insoluble cytoskeletal fraction within 10 s of thrombin stimulation. Chk and Lyn,
      but not Csk and c-Src, co-fractionated in the higher density lysate fractions of
      resting platelets, with Chk being found to localize close to CD36 (membrane
      glycoprotein IV)-anchored Lyn. The kinase activity of co-fractionated Lyn was
      suppressed 3-fold. In vitro phosphorylation assays showed that Chk suppressed Lyn
      activity by phosphorylating its C-terminal negative regulatory tyrosine. Upon
      stimulation of platelets with thrombin, the rapid and complete translocation of
      Chk away from Lyn caused concomitant activation of Lyn. This activation was
      accompanied by dephosphorylation of Lyn at its C-terminal negative regulatory
      tyrosine in cooperation with a protein tyrosine phosphatase. These results
      suggest that Chk, but not Csk, may function as a translocation-controlled
      negative regulator of CD36-anchored Lyn in thrombin-induced platelet activation.

PMID- 9171349
TI  - Abnormal mesoderm patterning in mouse embryos mutant for the SH2 tyrosine
      phosphatase Shp-2.
AB  - Shp-1, Shp-2 and corkscrew comprise a small family of cytoplasmic tyrosine
      phosphatases that possess two tandem SH2 domains. To investigate the biological
      functions of Shp-2, a targeted mutation has been introduced into the murine Shp-2
      gene, which results in an internal deletion of residues 46-110 in the N-terminal
      SH2 domain. Shp-2 is required for embryonic development, as mice homozygous for
      the mutant allele die in utero at mid-gestation. The Shp-2 mutant embryos fail to
      gastrulate properly as evidenced by defects in the node, notochord and posterior
      elongation. Biochemical analysis of mutant cells indicates that Shp-2 can
      function as either a positive or negative regulator of MAP kinase activation,
      depending on the specific receptor pathway stimulated. In particular, Shp-2 is
      required for full and sustained activation of the MAP kinase pathway following
      stimulation with fibroblast growth factor (FGF), raising the possibility that the
      phenotype of Shp-2 mutant embryos results from a defect in FGF-receptor
      signalling. Thus, Shp-2 modulates tyrosine kinase signalling in vivo and is
      crucial for gastrulation during mammalian development.

PMID- 9171352
TI  - Activation of c-Raf-1 by Ras and Src through different mechanisms: activation in
      vivo and in vitro.
AB  - The c-Raf-1 protein kinase plays a critical role in intracellular signaling
      downstream from many tyrosine kinase and G-protein-linked receptors. c-Raf-1
      binds to the proto-oncogene Ras in a GTP-dependent manner, but the exact
      mechanism of activation of c-Raf-1 by Ras is still unclear. We have established a
      system to study the activation of c-Raf-1 in vitro. This involves mixing
      membranes from cells expressing oncogenic H-RasG12V, with cytosol from cells
      expressing epitope-tagged full-length wild-type c-Raf-1. This results in a
      fraction of the c-Raf-1 binding to the membranes and a concomitant 10- to 20-fold
      increase in specific activity. Ras was the only component in these membranes
      required for activation, as purified recombinant farnesylated K-Ras.GTP, but not
      non-farnesylated K-Ras.GTP or farnesylated K-Ras.GDP, was able to activate c-Raf
      1 to the same degree as intact H-RasG12V membranes. The most potent activation
      occurred under conditions in which phosphorylation was prohibited. Under
      phosphorylation-permissive conditions, activation of c-Raf-1 by Ras was
      substantially inhibited. Consistent with the results from other groups, we find
      that the activation of c-Raf-1 by Src in vivo occurs concomitant with tyrosine
      phosphorylation on c-Raf-1, and in vitro, activation of c-Raf-1 by Src requires
      the presence of ATP. Therefore we propose that activation of c-Raf-1 by Ras or by
      Src occurs through different mechanisms.

PMID- 9171351
TI  - FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich
      ligands.
AB  - WW domains are conserved protein motifs of 38-40 amino acids found in a broad
      spectrum of proteins. They mediate protein-protein interactions by binding
      proline-rich modules in ligands. A 10 amino acid proline-rich portion of the
      morphogenic protein, formin, is bound in vitro by both the WW domain of the
      formin-binding protein 11 (FBP11) and the SH3 domain of Abl. To explore whether
      the FBP11 WW domain and Abl SH3 domain bind to similar ligands, we screened a
      mouse limb bud expression library for putative ligands of the FBP11 WW domain. In
      so doing, we identified eight ligands (WBP3 through WBP10), each of which
      contains a proline-rich region or regions. Peptide sequence comparisons of the
      ligands revealed a conserved motif of 10 amino acids that acts as a modular
      sequence binding the FBP11 WW domain, but not the WW domain of the putative
      signal transducing factor, hYAP65. Interestingly, the consensus ligand for the
      FBP11 WW domain contains residues that are also required for binding by the Abl
      SH3 domain. These findings support the notion that the FBP11 WW domain and the
      Abl SH3 domain can compete for the same proline-rich ligands and suggest that at
      least two subclasses of WW domains exist, namely those that bind a PPLP motif,
      and those that bind a PPXY motif.

PMID- 9171350
TI  - The coupling of alpha6beta4 integrin to Ras-MAP kinase pathways mediated by Shc
      controls keratinocyte proliferation.
AB  - The signaling pathways linking integrins to nuclear events are incompletely
      understood. We have examined intracellular signaling by the alpha6beta4 integrin,
      a laminin receptor expressed in basal keratinocytes and other cells. Ligation of
      alpha6beta4 in primary human keratinocytes caused tyrosine phosphorylation of
      Shc, recruitment of Grb2, activation of Ras and stimulation of the MAP kinases
      Erk and Jnk. In contrast, ligation of the laminin- and collagen-binding integrins
      alpha3beta1 and alpha2beta1 did not cause these events. While the stimulation of
      Erk by alpha6beta4 was suppressed by dominant-negative Shc, Ras and RhoA, the
      activation of Jnk was inhibited by dominant-negative Ras and Rac1 and by the
      phosphoinositide 3-kinase inhibitor Wortmannin. Adhesion mediated by alpha6beta4
      induced transcription from the Fos serum response element and promoted cell cycle
      progression in response to mitogens. In contrast, alpha3beta1- and alpha2beta1
      dependent adhesion did not induce these events. These findings suggest that the
      coupling of alpha6beta4 integrin to the control of cell cycle progression
      mediated by Shc regulates the proliferation of basal keratinocytes and possibly
      other cells which are in contact with the basement membrane in vivo.

PMID- 9171353
TI  - The GTPase Rho has a critical regulatory role in thymus development.
AB  - The present study employs a genetic approach to explore the role of Rho GTPases
      in murine thymic development. Inactivation of Rho function in the thymus was
      achieved by thymic targeting of a transgene encoding C3 transferase from
      Clostridium botulinum which selectively ADP-ribosylates Rho within its effector
      domain and thereby abolishes its biological function. Thymi lacking functional
      Rho isolated from C3 transgenic mice were strikingly smaller and showed a marked
      (90%) decrease in cellularity compared with their normal litter mates. We also
      observed a similar decrease in levels of peripheral T cells in C3 transgenic
      mice. Analysis of the maturation status of thymocytes indicated that
      differentiation of progenitor cells to mature T cells can occur in the absence of
      Rho function, and both positive and negative selection of T cells appear to be
      intact. However, transgenic mice that lack Rho function in the thymus show
      maturational, proliferative and cell survival defects during T-cell development
      that severely impair the generation of normal numbers of thymocytes and mature
      peripheral T cells. The present study thus identifies a role for Rho-dependent
      signalling pathways in thymocyte development. The data show that the function of
      Rho GTPases is critical for the proliferative expansion of thymocytes. This
      defines a selective role for the GTPase Rho in early thymic development as a
      critical integrator of proliferation and cell survival signals.

PMID- 9171354
TI  - An scl gene product lacking the transactivation domain induces bony abnormalities
      and cooperates with LMO1 to generate T-cell malignancies in transgenic mice.
AB  - The product of the scl (also called tal-1 or TCL5) gene is a basic domain, helix
      loop-helix (bHLH) transcription factor required for the development of
      hematopoietic cells. Additionally, scl gene disruption and dysregulation, by
      either chromosomal translocations or a site-specific interstitial deletion
      whereby 5' regulatory elements of the sil gene become juxtaposed to the body of
      the scl gene, is associated with T-cell acute lymphoblastic leukemia (ALL) and T
      cell lymphoblastic lymphoma. Here we show that an inappropriately expressed scl
      protein, driven by sil regulatory elements, can cause aggressive T-cell
      malignancies in collaboration with a misexpressed LMO1 protein, thus
      recapitulating the situation seen in a subset of human T-cell ALL. Moreover, we
      show that inappropriately expressed scl can interfere with the development of
      other tissues derived from mesoderm. Lastly, we show that an scl construct
      lacking the scl transactivation domain collaborates with misexpressed LMO1,
      demonstrating that the scl transactivation domain is dispensable for oncogenesis,
      and supporting the hypothesis that the scl gene product exerts its oncogenic
      action through a dominant-negative mechanism.

PMID- 9171355
TI  - A single serine residue at position 375 of VP16 is critical for complex assembly
      with Oct-1 and HCF and is a target of phosphorylation by casein kinase II.
AB  - We show that VP16 is phosphorylated by cellular kinases in vivo and in vitro and
      map the major sites of phosphorylation to be on serines towards the C-terminus,
      downstream of position 370 in both cases. Deletion of the acidic activation
      domain had no effect on phosphorylation, refining the sites to between position
      370 and 411. Within VP16, the C-terminal boundary for complex formation with Oct
      1 and HCF lies at position 388, and between 370 and 388 lies one serine, at
      position 375. This is a consensus casein kinase II (CKII) site and, using
      purified wild-type and mutant proteins, we show that it is the main CKII site in
      the body of the N-terminal complex-forming region. This site is also
      phosphorylated in nuclear extracts. Although other sites, mainly Ser411, are also
      phosphorylated by nuclear kinase(s), the single substitution of Ser375 to alanine
      abolishes CKII phosphorylation in vitro and virtually eliminates complex
      formation. This serine lies in a surface-exposed region of VP16 and, although
      complex formation is disrupted, other activities of the mutant are unaffected.
      Ser375 is also required in vivo where substitution to alanine abolishes
      transactivation, while replacement with threonine restores normal levels of
      activity.

PMID- 9171356
TI  - Molecular characterization of the B-box protein-protein interaction motif of the
      ETS-domain transcription factor Elk-1.
AB  - The ternary complex factor (TCF) subfamily of ETS-domain transcription factors
      form ternary complexes with the serum response factor (SRF) and the c-fos SRE.
      Extracellular signals are relayed via MAP kinase signal transduction pathways
      through the TCF component of the ternary complex. Protein-protein interactions
      between TCFs and SRF play an essential role in formation of this ternary complex.
      A 30 amino acid sequence encompassing the TCF B-box is sufficient to mediate
      interactions with SRF. In this study we have identified amino acids which are
      critical for this interaction and derived a molecular model of the SRF binding
      interface. Alanine scanning of the Elk-1 B-box reveals five predominantly
      hydrophobic residues which are essential for binding to SRF and for ternary
      complex formation in vitro and in vivo. These amino acids are predicted to lie on
      one face of an alpha-helix. Peptides encompassing the B-box retain biological
      activity and have helix-forming propensity. alpha-Helix and ternary complex
      formation is disrupted by the introduction of helix-breaking proline residues.
      Our results are consistent with a model in which the Elk-1 B-box forms an
      inducible alpha-helix which presents a hydrophobic face for interaction with SRF.
      We discuss the wider applicability of our results to similar short protein
      protein interaction motifs found in other transcription factors.

PMID- 9171357
TI  - Assembly of a bZIP-bHLH transcription activation complex: formation of the yeast
      Cbf1-Met4-Met28 complex is regulated through Met28 stimulation of Cbf1 DNA
      binding.
AB  - Transcriptional activation of sulfur amino acid metabolism in yeast is dependent
      on a multi-functional factor, the centromere-binding factor 1 (Cbf1) and on two
      specific transcription factors, Met4 and Met28. Cbf1 belongs to the basic helix
      loop-helix DNA-binding protein family while Met4 and Met28 are two basic leucine
      zipper (bZIP) factors. We have shown previously that in cell extracts, the three
      factors are found in a high molecular weight complex. By using mobility shift
      assays, we report here that the in vitro reconstitution of the Cbf1-Met4-Met28
      complex on MET16UAS can be obtained with purified recombinant proteins. DNase I
      protection experiments confirm that the Cbf1-Met4-Met28 complex is formed over
      the TCACGTG sequence. The experiments also show that both Met4 and Met28 bind to
      DNA only in the presence of Cbf1. Moreover, Met28 is shown to enhance the DNA
      binding activity of Cbf1. Analysis of MET28 gene regulation reveals that its
      expression requires Met4. Thus the biochemical activity of Met28 allows the
      establishment of a positive regulatory loop. The results thus provide evidence of
      a new functional relationship between bHLH and bZIP proteins and demonstrate that
      the association of such factors may serve to discriminate between the different
      TCACGTG sequences found in the chromosomes.

PMID- 9171358
TI  - Multiple functions of Drosophila heat shock transcription factor in vivo.
AB  - Heat shock transcription factor (HSF) is a transcriptional activator of heat
      shock protein (hsp) genes in eukaryotes. In order to elucidate the physiological
      functions of HSF in Drosophila, we have isolated lethal mutations in the hsf
      gene. Using a conditional allele, we show that HSF has an essential role in the
      ability of the organism to survive extreme heat stress. In contrast to previous
      results obtained with yeast HSF, the Drosophila protein is dispensable for
      general cell growth or viability. However, it is required under normal growth
      conditions for oogenesis and early larval development. These two developmental
      functions of Drosophila HSF are genetically separable and appear not to be
      mediated through the induction of HSPs, implicating a novel action of HSF that
      may be unrelated to its characteristic function as a stress-responsive
      transcriptional activator.

PMID- 9171359
TI  - Stable co-occupancy of transcription factors and histones at the HIV-1 enhancer.
AB  - To investigate mechanisms yielding DNase I-hypersensitive sites (DHSs) at gene
      regulatory regions, we have initiated a biochemical analysis of transcription
      factor binding and nucleosome remodeling with a region of the human
      immunodeficiency virus 1 (HIV-1) 5' long terminal repeat (LTR) that harbors
      constitutive DHSs in vivo. In vitro reconstitution of an HIV-1 5' LTR fragment
      into nucleosome core particles demonstrates that Sp1, NF-kappaB1, LEF-1, ETS-1
      and USF can gain access to their binding sites in HIV-1 nucleosomal DNA. The
      factor-bound mononucleosomes resist histone displacement from the DNA by the
      chromatin remodeling activity, SW1-SNF, or the histone chaperone, nucleoplasmin,
      suggesting that the binding of these factors to nucleosomal HIV-1 sequences forms
      a stable complex that includes the underlying histones. However, when the HIV-1
      5' LTR fragment is incorporated into a nucleosomal array, Sp1 and NF-kappaB1
      binding produce regions of enhanced DNase I sensitivity specifically at the HIV-1
      nucleosome. These regions resemble the observed in vivo DHSs, yet the HIV-1
      nucleosome remains intact even in the presence of nucleoplasmin. Thus, the
      constitutive DHSs identified at the HIV-1 enhancer in native chromatin may
      reflect the presence of a ternary complex composed of transcriptional activators,
      histones and DNA.

PMID- 9171360
TI  - Structure of the chromatin binding (chromo) domain from mouse modifier protein 1.
AB  - The structure of a chromatin binding domain from mouse chromatin modifier protein
      1 (MoMOD1) was determined using nuclear magnetic resonance (NMR) spectroscopy.
      The protein consists of an N-terminal three-stranded anti-parallel beta-sheet
      which folds against a C-terminal alpha-helix. The structure reveals an unexpected
      homology to two archaebacterial DNA binding proteins which are also involved in
      chromatin structure. Structural comparisons suggest that chromo domains, of which
      more than 40 are now known, act as protein interaction motifs and that the MoMOD1
      protein acts as an adaptor mediating interactions between different proteins.

PMID- 9171361
TI  - Recognition of AUG and alternative initiator codons is augmented by G in position
      +4 but is not generally affected by the nucleotides in positions +5 and +6.
AB  - A primer extension (toeprinting) assay was used to monitor selection by ribosomes
      of the first versus the second AUG codon as a function of introducing mutations
      on the 3' side (positions +4, +5 and +6) of the first AUG codon. Six different
      flanking codons starting with G (GCG, GCU, GCC, GCA, GAU and GGA) strongly
      augmented selection of AUG#1 when compared with matched mRNAs that had A or C
      instead of G in position +4. Augmentation by G in position +4 failed only when it
      was combined with U in position +5, as in the sequence augGUA. In contrast with
      the usual enhancing effect of introducing G in position +4, most mutations in
      position +5 had no discernible effect, as shown with the series augANA (where N =
      C, A, G or U) and the series augCNA. AUG codon recognition was also unaffected by
      mutations in position +6, as shown by testing four mRNAs that had augCCN as the
      start site. Thus the primary sequence context that augments the recognition of
      AUG start codons does not appear generally to extend beyond G in position +4.
      When the toeprinting assay was used with mRNAs that initiate translation at CUG
      instead of AUG, cugGAU was not recognized better than cugGGU, contradicting the
      hypothesis that initiation at non-AUG codons might be favored by A instead of G
      in position +5.

PMID- 9171362
TI  - Histone octamer function in vivo: mutations in the dimer-tetramer interfaces
      disrupt both gene activation and repression.
AB  - Within the core histone octamer each histone H4 interacts with each H2A-H2B dimer
      subunit through two binding surfaces. Tyrosines play a central role in these
      interactions with H4 tyrosines 72 and 88 contacting one H2A-H2B dimer subunit,
      and tyrosine 98 contacting the other. To investigate the roles of these
      interactions in vivo, we made site-directed amino acid substitutions at each of
      these tyrosine residues. Elimination of either set of interactions is lethal,
      suggesting that binding of the tetramer to both dimers is essential. Temperature
      sensitive mutants were obtained through single amino acid substitutions at each
      of the tyrosines. The mutants show both strong positive and negative effects on
      transcription. Positive effects include Spt- and Sin-phenotypes resulting from
      mutations at each of the three tyrosines. One allele has a strong negative effect
      on the expression of genes essential for the G1 cell cycle transition. At
      restrictive temperature, mutant cells fail to express the CLN1, CLN2, SWI4 and
      SWI6 genes, and have reduced levels of CLN3 mRNA. These results demonstrate the
      critical role of histone dimer-tetramer interactions in vivo, and define their
      essential role in the expression of genes regulating G1 cell cycle progression.

PMID- 9171363
TI  - Developmentally regulated initiation of DNA synthesis by telomerase: evidence for
      factor-assisted de novo telomere formation.
AB  - Telomerase serves a dual role at telomeres, maintaining tracts of telomere
      repeats and forming telomeres de novo on broken chromosomes in a process called
      chromosome healing. In ciliates, both mechanisms are readily observed.
      Vegetatively growing cells maintain pre-existing telomeres, while cells
      undergoing macronuclear development fragment their chromosomes and form telomeres
      de novo. Here we provide the first evidence for developmentally regulated
      initiation of DNA synthesis by telomerase. In vitro assays were conducted with
      telomerase from vegetative and developing Euplotes macronuclei using chimeric
      primers that contained non-telomeric 3' ends and an upstream stretch of telomeric
      DNA. In developing macronuclei, chimeric primers had two fates: nucleotides were
      either polymerized directly onto the 3' terminus or residues were removed from
      the 3' end by endonucleolytic cleavage before polymerization began. In contrast,
      telomerase from vegetative macronuclei used only the cleavage pathway. Telomere
      repeat addition onto non-telomeric 3' ends was lost when developing macronuclei
      were lysed and the contents purified on glycerol gradients. However, when
      fractions from the glycerol gradient were added back to partially purified
      telomerase, telomere synthesis was restored. The data indicate that a dissociable
      chromosome healing factor (CHF) collaborates with telomerase to initiate
      developmentally programmed de novo telomere formation.

PMID- 9171364
TI  - Protein-primed DNA replication: a transition between two modes of priming by a
      unique DNA polymerase.
AB  - Phage phi29 from Bacillus subtilis is a paradigm of the protein-primed
      replication mechanism, in which a single-subunit DNA polymerase is involved in
      both the specific protein-primed initiation step and normal DNA elongation. To
      start phi29 DNA replication, the viral DNA polymerase must interact with a free
      molecule of the viral terminal protein (TP), to prime DNA synthesis once at each
      phi29 DNA end. The results shown in this paper demonstrate that the DNA
      polymerase-primer TP heterodimer is not dissociated immediately after initiation.
      On the contrary, there is a transition stage in which the DNA polymerase
      synthesizes a five nucleotide-long DNA molecule while complexed with the primer
      TP, undergoes some structural change during replication of nucleotides 6-9, and
      finally dissociates from the primer protein when nucleotide 10 is inserted onto
      the nascent DNA chain. This behaviour probably reflects the polymerase
      requirement for a DNA primer of a minimum length to efficiently catalyze DNA
      elongation. The significance of such a limiting transition stage is supported by
      the finding of abortive replication products consisting of the primer TP linked
      up to eight nucleotides, detected during in vitro replication of phi29 TP-DNA
      particularly under conditions that decrease the strand-displacement capacity of
      phi29 DNA polymerase.

PMID- 9171365
TI  - Near-simultaneous DNA cleavage by the subunits of the junction-resolving enzyme
      T4 endonuclease VII.
AB  - In common with a number of other DNA junction-resolving enzymes, endonuclease VII
      of bacteriophage T4 binds to a four-way DNA junction as a dimer, and cleaves two
      strands of the junction. We have used a supercoil-stabilized cruciform substrate
      to probe the simultaneity of cleavage at the two sites. Active endonuclease VII
      converts the supercoiled circular DNA directly into linear product, indicating
      that the two cleavage reactions must occur within the lifetime of the protein
      junction complex. By contrast, a heterodimer of active enzyme and an inactive
      mutant endonuclease VII leads to the formation of nicked circular product,
      showing that the subunits operate fully independently.

PMID- 9171366
TI  - Recombinational repair in yeast: functional interactions between Rad51 and Rad54
      proteins.
AB  - Rad51p is a eukaryotic homolog of RecA, the central homologous pairing and strand
      exchange protein in Escherichia coli. Rad54p belongs to the Swi2p/Snf2p family of
      DNA-stimulated ATPases. Both proteins are also important members of the RAD52
      group which controls recombinational DNA damage repair of double-strand breaks
      and other DNA lesions in Saccharomyces cerevisiae. Here we demonstrate by
      genetic, molecular and biochemical criteria that Rad51 and Rad54 proteins
      interact. Strikingly, overexpression of Rad54p can functionally suppress the UV
      and methyl methanesulfonate sensitivity caused by a deletion of the RAD51 gene.
      However, no suppression was observed for the defects of rad51 cells in the repair
      of gamma-ray-induced DNA damage, mating type switching or spontaneous hetero
      allelic recombination. This suppression is genetically dependent on the presence
      of two other members of the recombinational repair group, RAD55 and RAD57. Our
      data provide compelling evidence that Rad51 and Rad54 proteins interact in vivo
      and that this interaction is functionally important for recombinational DNA
      damage repair. As both proteins are conserved throughout evolution from yeasts to
      humans, a similar protein-protein interaction may be expected in other organisms.

PMID- 9171367
TI  - POU domain family values: flexibility, partnerships, and developmental codes.

PMID- 9171368
TI  - Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal
      phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous
      embryos.
AB  - Mutations of the human BRCA1 and BRCA2 genes encoding tumor suppressors have been
      implicated in inherited predisposition to breast and other cancers. Disruption of
      the homologous mouse genes Brca1 and Brca2 by targeting showed that they both
      have indispensable roles during embryogenesis, because nullizygous embryos become
      developmentally retarded and disorganized, and die early in development. In Brca1
      mutants, the onset of abnormalities is earlier by one day and their phenotypic
      features and time of death are highly variable, whereas the phenotype of Brca2
      null embryos is more uniform, and they all survive for at least 8.5 embryonic
      days. Observations with Brca1/Brca2 double nullizygotes raise the possibility
      that the two developmental pathways could be linked. Interestingly, the impact of
      the Brca1 or Brca2 null mutation is less severe in a p53 null background.

PMID- 9171369
TI  - Brca2 is required for embryonic cellular proliferation in the mouse.
AB  - Mutations of the tumor suppressor gene BRCA2 are associated with predisposition
      to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of
      the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5
      of embryogenesis. Mutant phenotypes range from severely developmentally retarded
      embryos that do not gastrulate to embryos with reduced size that make mesoderm
      and survive until 8.5 days of development. Although apoptosis is normal, cellular
      proliferation is impaired in Brca2(10-11) mutants, both in vivo and in vitro. In
      addition, the expression of the cyclin-dependent kinase inhibitor p21 is
      increased. Thus, Brca2(10-11) mutants are similar in phenotype to Brca1(5-6)
      mutants but less severely affected. Expression of either of these two genes was
      unaffected in mutant embryos of the other. This study shows that Brca2, like
      Brca1, is required for cellular proliferation during embryogenesis. The
      similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes
      may have cooperative roles or convergent functions during embryogenesis.

PMID- 9171370
TI  - The Nf2 tumor suppressor gene product is essential for extraembryonic development
      immediately prior to gastrulation.
AB  - The neurofibromatosis type II (NF2) tumor suppressor encodes a putative
      cytoskeletal associated protein, the loss of which leads to the development of
      Schwann cell tumors associated with NF2 in humans. The NF2 protein merlin belongs
      to the band 4.1 family of proteins that link membrane proteins to the
      cytoskeleton and are thought to be involved in dynamic cytoskeletal
      reorganization. Beyond its membership in this family, however, the function of
      merlin remains poorly understood. In order to analyze the function of merlin
      during embryogenesis and to develop a system to study merlin function in detail,
      we have disrupted the mouse Nf2 gene by homologous recombination in embryonic
      stem cells. Most embryos homozygous for a mutation at the Nf2 locus fail between
      embryonic days 6.5 and 7.0, exhibiting a collapsed extraembryonic region and the
      absence of organized extraembryonic ectoderm. The embryo proper continues to
      develop, but fails to initiate gastrulation. These observations are supported by
      the expression patterns of markers of the extraembryonic lineage and the lack of
      expression of mesodermal markers in the mutant embryos. Mosaic studies
      demonstrate that merlin function is not required cell autonomously in mesoderm,
      and support the proposition that merlin function is essential for the development
      of extraembryonic structures during early mouse development.

PMID- 9171371
TI  - Oncogene-dependent apoptosis in extracts from drug-resistant cells.
AB  - Many genotoxic agents kill tumor cells by inducing apoptosis; hence, mutations
      that suppress apoptosis produce resistance to chemotherapy. Although directly
      activating the apoptotic machinery may bypass these mutations, how to achieve
      this activation in cancer cells selectively is not clear. In this study, we show
      that the drug-resistant 293 cell line is unable to activate components of the
      apoptotic machinery-the ICE-like proteases (caspases)-following treatment with an
      anticancer drug. Remarkably, extracts from untreated cells spontaneously activate
      caspases and induce apoptosis in a cell-free system, indicating that drug
      resistant cells have not only the apoptotic machinery but also its activator.
      Comparing extracts from cells with defined genetic differences, we show that this
      activator is generated by the adenovirus E1A oncogene and is absent from normal
      cells. We provide preliminary characterization of this oncogene generated
      activity (OGA) and show that partially purified OGA activates caspases when added
      to extracts from untransformed cells. We suggest that agents that link OGA to
      caspases in cells would kill tumor cells otherwise resistant to conventional
      cancer therapy. As this killing relies on an activity generated by an oncogene,
      the effect of these agents should be selective for transformed cells.

PMID- 9171372
TI  - A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters
      activates M/G1-specific transcription.
AB  - We have identified a novel promoter element that confers M/G1-specific
      transcription in Saccharomyces cerevisiae. This element, which we call an ECB
      (early cell cycle box), was first identified in the SWI4 promoter, but it is also
      present in the promoter of a G1 cyclin CLN3, as well as in the promoters of three
      DNA replication genes: CDC6, CDC47, and CDC46. Transcripts from all five of these
      genes oscillate during the cell cycle and peak at the M/G1 boundary, as do
      isolated ECB elements in reporter constructs. The ECB element contains an Mcm1
      binding site to which Mcm1 binds in vitro, and an Mcm1-VP16 fusion, which places
      a constitutive activator on Mcm1-binding sites in vivo, can deregulate ECB
      containing promoters. Mcm1 is a transcription factor that is also required for
      minichromosome maintenance. We provide evidence that the replication defect of
      mcm1 mutants can be suppressed by ectopic CDC6 transcription. Periodic expression
      of SWI4 and CLN3 may be important for cell cycle progression, as we find that
      these genes are both haploinsufficient and rate limiting for G1 progression. We
      suggest that ECB-regulated gene products play critical roles in promoting the
      initiation of S-phase, both by regulating CLN1 and CLN2 transcription and as
      components of the initiation complex on origins of replication.

PMID- 9171373
TI  - roughex down-regulates G2 cyclins in G1.
AB  - Cell cycle arrest in G1 at the onset of patterning in the Drosophila eye is
      mediated by roughex. In roughex mutants, cells accumulate Cyclin A protein in
      early G1 and progress into S phase precociously. When Roughex is overexpressed in
      S/G2 cells, Cyclin A is mislocalized to the nucleus and degraded, preventing
      mitosis. Whereas Roughex inhibits Cyclin A accumulation, Cyclin E down-regulates
      Roughex protein in vivo. Roughex binds to Cyclin E and is a substrate for a
      Cyclin E-Cdk complex in vitro. These data argue that Roughex inhibits Cyclin A
      accumulation in early G1 by targeting Cyclin A for destruction. In late G1,
      Roughex is destabilized in a Cyclin E-dependent process, releasing Cyclin A for
      its role in S/G2.

PMID- 9171374
TI  - Nuclear entry, oligomerization, and DNA binding of the Drosophila heat shock
      transcription factor are regulated by a unique nuclear localization sequence.
AB  - In normally growing Drosophila cultured cells the Drosophila heat shock
      transcription factor (dHSF) is localized in the cytosol and translocates into the
      nucleus after heat shock. In the cytosol of nonshocked cells, the dHSF is present
      as a monomer that cannot bind DNA. Upon stress, the dHSF enters the nucleus where
      it is observed to be a trimer. A novel nuclear localization sequence (NLS) in the
      dHSF was found to be responsible for stress-dependent nuclear entry. Deletion of
      the NLS prevents nuclear entry, as expected, yet surprisingly also allows
      constitutive oligomerization and DNA binding in the cytosol. Further analysis of
      the NLS by mutagenesis suggests that the two functions of nuclear entry and
      oligomerization are separable in that distinct residues present in the NLS are
      responsible for each. Mutations in certain basic residues completely block
      nuclear entry, as expected for a constitutive NLS. In addition, two residues were
      found in the NLS that, when altered, allowed constitutive nuclear entry of dHSF
      independent of stress. These residues may interact with a putative cellular
      component or possibly other domains of the HSF to prevent nuclear entry in
      normally growing cells. The NLS can also function autonomously to target a beta
      galactosidase fusion protein into the nucleus in a heat shock-dependent fashion.

PMID- 9171375
TI  - Three human RNA polymerase III-specific subunits form a subcomplex with a
      selective function in specific transcription initiation.
AB  - Transcription by RNA polymerase III involves recruitment of the polymerase by
      template-bound accessory factors, followed by initiation, elongation, and
      termination steps. An immunopurification approach has been used to demonstrate
      that human RNA Pol III is composed of 16 subunits, some of which are apparently
      modified in HeLa cells. Partial denaturing conditions and sucrose gradient
      sedimentation at high salt result in the dissociation of a subcomplex that
      includes hRPC32, hRPC39, and hRPC62. Cognate cDNAs were isolated and shown to
      encode three subunits that are specific to RNA Pol III and homologous to three
      yeast subunits. The human RNA Pol III core lacking the subcomplex functions in
      transcription elongation and termination following nonspecific initiation on a
      tailed template, but fails to show promoter-dependent transcription initiation in
      conjunction with accessory factors. The capability for specific transcription
      initiation can be restored either by the natural subcomplex or by a stable
      subcomplex composed of recombinant hRPC32, hRPC39, and hRPC62 polypeptides. One
      component (hRPC39) of this subcomplex interacts physically with both hTBP and
      hTFIIIB90, two subunits of human RNA Pol III transcription initiation factor
      IIIB. These data strongly suggest that the hRPC32-hRPC39-hRPC62 subcomplex
      directs RNA Pol III binding to the TFIIIB-DNA complex via the interactions
      between TFIIIB and hRPC39.

PMID- 9171376
TI  - A role for phosphorylation by casein kinase II in modulating Antennapedia
      activity in Drosophila.
AB  - We present evidence that the in vivo activity of the HOX protein Antennapedia
      (ANTP) is modified because of phosphorylation by the serine/threonine kinase
      casein kinase II (CKII). Using an in vivo assay a form of ANTP that has alanine
      substitutions at its CKII target sites has, in addition to wild-type ANTP
      functions, the ability to alter severely thoracic and abdominal development. The
      novel functions of this protein suggest that this form of ANTP is not suppressed
      phenotypically by the more posterior homeotic proteins. In contrast, the in vivo
      activity of a form of ANTP that contains acidic amino acid substitutions at its
      CKII target sites, thereby mimicking a constitutively phosphorylated ANTP
      protein, is greatly reduced. This hypoactive form of ANTP, but not the alanine
      substituted form, is also reduced in its ability to bind to DNA cooperatively
      with the homeodomain protein Extradenticle. Our results suggest that
      phosphorylation of ANTP by CKII is important for preventing inappropriate
      activities of this homeotic protein during embryogenesis.

PMID- 9171377
TI  - strawberry notch encodes a conserved nuclear protein that functions downstream of
      Notch and regulates gene expression along the developing wing margin of
      Drosophila.
AB  - The dorsal/ventral (D/V) boundary functions as an organizer in the growth and
      patterning of the Drosophila wing disc and gives rise to the wing margin in the
      adult fly. Here we show that strawberry notch (sno) is a downstream component of
      the Notch signaling pathway and is important for the specification of this
      organizer. sno encodes a novel nuclear protein conserved in C. elegans, mouse,
      and humans. Mutations in wing margin genes interact dominantly with sno and loss
      of sno function results in loss of expression of wingless, vestigial, cut, and
      E(spl)-m8 at the D/V boundary. In regulating these genes, sno functions in close
      cooperation with Suppressor of Hairless and Hairless. Finally, sno has no role in
      lateral inhibition suggesting that it may contribute to the specificity between
      lateral and inductive Notch signaling pathways.

PMID- 9171378
TI  - Extracellular secretion of Escherichia coli heat-stable enterotoxin I across the
      outer membrane.
AB  - Escherichia coli heat-stable enterotoxin Ip (STIp) is an extracellular toxin
      consisting of 18 amino acid residues that is synthesized as a precursor of pre
      (amino acid residues 1 to 19), pro (amino acid residues 20 to 54), and mature
      (amino acid residues 55 to 72) regions. The precursor synthesized in the
      cytoplasm is translocated across the inner membrane by the general export pathway
      consisting of Sec proteins. The pre region functions as a leader peptide and is
      cleaved during translocation. However, it remains unknown how the resulting
      peptide (pro-mature peptide) translocates across the outer membrane. In this
      study, we investigated the structure of the STIp that passes through the outer
      membrane to determine how it translocates through the outer membrane. The results
      showed that the pro region is cleaved in the periplasmic space. The generated
      peptide becomes the mature form of STIp, which happens to have disulfide bonds,
      which then passes through the outer membrane. We also showed that STIp with a
      carboxy-terminal peptide consisting of 3 amino acid residues passes through the
      outer membrane, whereas STIp with a peptide composed of 37 residues does not.
      Amino acid analysis of mutant STIp purified from culture supernatant revealed
      that the peptide composed of 37 amino acid residues was cleaved into fragments of
      5 amino acid residues. In addition, analyses of STIps with a mutation at the
      cysteine residue and the dsbA mutant strain revealed that the formation of an
      intramolecular disulfide bond within STIp is not absolutely required for the
      mature region of STIp to pass through the outer membrane.

PMID- 9171379
TI  - Identification of essential amino acids in the Streptococcus mutans
      glucosyltransferases.
AB  - A comparison of the amino acid sequences of the glucosyltransferases (GTFs) of
      mutans streptococci with those from the alpha-amylase family of enzymes revealed
      a number of conserved amino acid positions which have been implicated as
      essential in catalysis. Utilizing a site-directed mutagenesis approach with the
      GTF-I enzyme of Streptococcus mutans GS-5, we identified three of these conserved
      amino acid positions, Asp413, Trp491, and His561, as being important in enzymatic
      activity. Mutagenesis of Asp413 to Thr resulted in a GTF which expressed only
      about 12% of the wild-type activity. In contrast, mutagenesis of Asp411 did not
      inhibit enzyme activity. In addition, the D413T mutant was less stable than was
      the parental enzyme when expressed in Escherichia coli. Moreover, conversion of
      Trp491 or His561 to either Gly or Ala resulted in enzymes devoid of GTF activity,
      indicating the essential nature of these two amino acids for activity.
      Furthermore, mutagenesis of the four Tyr residues present at positions 169 to 172
      which are part of a subdomain with homology to the direct repeating sequences
      present in the glucan-binding domain of the GTFs had little overall effect on
      enzymatic activity, although the glucan products appeared to be less adhesive.
      These results are discussed relative to the mechanisms of catalysis proposed for
      the GTFs and related enzymes.

PMID- 9171381
TI  - Delineation of the interaction domains of Agrobacterium tumefaciens VirB7 and
      VirB9 by use of the yeast two-hybrid assay.
AB  - The Agrobacterium tumefaciens VirB proteins are postulated to form a transport
      pore for the transfer of T-DNA. Formation of the transport pore will involve
      interactions among the VirB proteins. A powerful genetic method to study protein
      protein interaction is the yeast two-hybrid assay. To test whether this method
      can be used to study interactions among the VirB membrane proteins, we studied
      the interaction of VirB7 and VirB9 in yeast. We recently demonstrated that VirB7
      and VirB9 form a protein complex linked by a disulfide bond between cysteine 24
      of VirB7 and cysteine 262 of VirB9 (L. Anderson, A. Hertzel, and A. Das, Proc.
      Natl. Acad. Sci. USA 93:8889-8894, 1996). We now demonstrate that VirB7 and VirB9
      interact in yeast, and this interaction does not require the cysteine residues
      essential for the disulfide linkage. By using defined segments in fusion
      constructions, we mapped the VirB7 interaction domain of VirB9 to residues 173 to
      275. In tumor formation assays, both virB7C24S and virB9C262S expressed from a
      multicopy plasmid complemented the respective deletion mutation, indicating that
      the cysteine residues may not be essential for DNA transfer.

PMID- 9171380
TI  - Cloning and characterization of two immunophilin-like genes, ilpA and fkpA, on a
      single 3.9-kilobase fragment of Aeromonas hydrophila genomic DNA.
AB  - Antiserum to Aeromonas hydrophila A6 cell envelopes was shown in a previous study
      (C. Y. F. Wong, G. Mayrhofer, M. W. Heuzenroeder, H. M. Atkinson, D. M. Quinn,
      and R. L. P. Flower, FEMS Immunol. Med. Microbiol. 15:233-241, 1996) to protect
      mice against lethal infection by this organism. In this study, colony blot
      analysis of an A. hydrophila genomic library using antiserum to A. hydrophila A6
      cell envelopes revealed a cosmid clone expressing a 30-kDa protein which has not
      been described previously in aeromonads. The nucleotide sequence of a 3.9-kb
      fragment derived from this cosmid which expressed the 30-kDa protein revealed two
      potential open reading frames (ORFs) with homology to known immunophilin
      proteins. ORF1 encoded a 212-amino-acid protein (molecular mass, 22.4 kDa) with
      56% identity to the immunophilin SlyD protein of Escherichia coli. ORF1 was
      subsequently designated ilpA (immunophilin-like protein). ORF3 encoded a
      potential gene product of 268 amino acids with a typical signal sequence and a
      predicted molecular size of 28.7 kDa. The inferred amino acid sequence showed 46%
      identity with the sequence of the FkpA protein of E. coli and 40% identity with
      the sequence of the macrophage infectivity potentiator (Mip) protein of
      Legionella pneumophila. ORF3 was designated fkpA (FK506 binding protein) by
      analogy with the E. coli FkpA protein. Expression of the FkpA protein was
      confirmed by Western blot (immunoblot) analysis, which detected a 30-kDa protein,
      with antiserum to the Mip protein of Legionella longbeachae and a specific
      antiserum to anA. hydrophila 30-kDa membrane protein. PCR and Southern analysis
      showed that a DNA sequence encoding FkpA was found in all 178 aeromonads of
      diverse origins tested. A nonpolar insertion mutation in the fkpA gene did not
      attenuate virulence in a suckling mouse model nor did it affect the expression of
      hemolysins or DNase. This suggests that either the fkpA gene is not essential in
      the virulence of A. hydrophila under these conditions or there are other genes in
      A. hydrophila coding for proteins with similar functions.

PMID- 9171382
TI  - Cloning and analysis of the pepV dipeptidase gene of Lactococcus lactis MG1363.
AB  - The gene pepV, encoding a dipeptidase from Lactococcus lactis subsp. cremoris
      MG1363, was identified in a genomic library in pUC19 in a peptidase-deficient
      Escherichia coli strain and subsequently sequenced. PepV of L. lactis is
      enzymatically active in E. coli and hydrolyzes a broad range of dipeptides but no
      tri-, tetra-, or larger oligopeptides. Northern (RNA) and primer extension
      analyses indicate that pepV is a monocistronic transcriptional unit starting 24
      bases upstream of the AUG translational start codon. The dipeptidase of L. lactis
      was shown to be similar to the dipeptidase encoded by pepV of L. delbrueckii
      subsp. lactis, with 46% identity in the deduced amino acid sequences. A PepV
      negative mutant of L. lactis was constructed by single-crossover recombination.
      Growth of the mutant strain in milk was significantly slower than that of the
      wild type, but the strains ultimately reached the same final cell densities.

PMID- 9171383
TI  - Cross regulation of four GATA factors that control nitrogen catabolic gene
      expression in Saccharomyces cerevisiae.
AB  - Nitrogen catabolic gene expression in Saccharomyces cerevisiae has been reported
      to be regulated by three GATA family proteins, the positive regulators Gln3p and
      Gat1p/Nil1p and the negative regulator Dal80p/Uga43p. We show here that a fourth
      member of the yeast GATA family, the Dal80p homolog Deh1p, also negatively
      regulates expression of some, but not all, nitrogen catabolic genes, i.e., GAP1,
      DAL80, and UGA4 expression increases in a deh1 delta mutant. Consistent with
      Deh1p regulation of these genes is the observation that Deh1p forms specific DNA
      protein complexes with GATAA-containing UGA4 and GAP1 promoter fragments in
      electrophoretic mobility shift assays. Deh1p function is demonstrable, however,
      only when a repressive nitrogen source such as glutamine is present; deh1 delta
      mutants exhibit no detectable phenotype with a poor nitrogen source such as
      proline. Our experiments also demonstrate that GATA factor gene expression is
      highly regulated by the GATA factors themselves in an interdependent manner.
      DAL80 expression is Gln3p and Gat1p dependent and Dal80p regulated. Moreover,
      Gln3p and Dal80p bind to DAL80 promoter fragments. In turn, GAT1 expression is
      Gln3p dependent and Dal80p regulated but is not autogenously regulated like
      DAL80. DEH1 expression is largely Gln3p independent, modestly Gat1p dependent,
      and most highly regulated by Dal80p. Paradoxically, the high-level DEH1
      expression observed in a dal80::hisG disruption mutant is highly sensitive to
      nitrogen catabolite repression.

PMID- 9171384
TI  - Lipid and fatty acid composition of cytoplasmic membranes from Streptomyces
      hygroscopicus and its stable protoplast-type L form.
AB  - The cells of an L-form strain of Streptomyces hygroscopicus have been grown for
      20 years without a cell wall. Their cytoplasmic membranes have high stability and
      an unusual structural polymorphism. To clarify the importance of the lipid
      components for these membrane properties, a comparative analysis has been carried
      out with purified membranes of L-form cells, of parent vegetative hyphal cells (N
      form cells), and of protoplasts derived from the latter. The phospholipid classes
      and fatty acids were determined by thin-layer chromatography (TLC), two
      dimensional TLC, high-performance liquid chromatography, gas chromatography, and
      mass spectrometry. The qualitative compositions of cardiolipin (CL), lyso
      cardiolipin (LCL), phosphatidylethanolamine (PE1 and PE2), lyso
      phosphatidylethanolamine (LPE), phosphatidylinositolmannoside (PIM), phosphatidic
      acid (PA), dilyso-cardiolipin-phosphatidylinositol (DLCL-PI), and the 13 main
      fatty acids were the same in the three membrane types. However, significant
      quantitative differences were observed in the L-form membrane. They consist of a
      three- to fourfold-higher content of total, extractable lipids, 20% more
      phospholipids, an increased content of CL and PIM, and a reduced amount of the
      component DLCL-PI. Furthermore, the L-form membrane is characterized by a higher
      content of branched anteiso 15:0 and anteiso 17:0 fatty acids compared to that of
      the membranes of the walled vegetative cells. These fatty acids have lower
      melting points than their straight and iso-branched counterparts and make the
      membrane more fluid. The phospholipid composition of the protoplast membrane
      differs quantitatively from that of the N form and the L form. Whereas the
      phospholipid classes are mostly similar to that of the N form, the fatty acid
      pattern tends to be closer to that of the L-form membrane. The membranes of both
      the L-form cells and the protoplasts need to be more fluid because of their
      spherical cell shape and higher degree of curvature compared with N-form
      membranes.

PMID- 9171385
TI  - Structural characterization of molecular phospholipid species in cytoplasmic
      membranes of the cell wall-less Streptomyces hygroscopicus L form by use of
      electrospray ionization coupled with collision-induced dissociation mass
      spectrometry.
AB  - A comparative analysis of the lipid compositions and fatty acids in the
      cytoplasmic membranes of Streptomyces hygroscopicus and its stable cell wall-less
      L form has been carried out to detect the differences which may be involved in
      the altered properties of the L-form membranes. Because only quantitative
      differences could be found (8), we analyzed the lipid components at the molecular
      level. Electrospray ionization (ESI), collision-induced dissociation (CID), and
      tandem mass spectrometry (MS-MS) were used for qualitative detection and
      quantitative determination of the molecular lipid species in
      phosphatidylethanolamine (PE1), lyso-cardiolipin (LCL), and cardiolipin (CL).
      Each phospholipid, isolated by preparative high-performance liquid chromatography
      showed several homologous molecular ion groups (PE1, four groups; LCL, six
      groups; CL, six groups) in the negative ESI-MS spectra. The sizes of the peaks
      represent their relative amounts in the corresponding phospholipid classes.
      Structural details about individual components of the molecular ion groups were
      obtained by mass selection and CID with MS-MS. Product ions derived from CID
      (daughter ions) give information about the molecular weights of the acyl
      constituents. The qualitative and quantitative compositions of the molecular
      species were determined by combining the data from the fatty acid pattern
      obtained by gas chromatography (GC), the relative quantities of the molecular ion
      groups, and the acyl constituents detected in these molecular ions. Because the
      ESI-MS-CID-MS data do not allow us to distinguish between n, iso, and anteiso
      fatty acids of the same molecular weight, it has been assumed that the ratio of
      these equal-numbered fatty acids determined by GC analysis of the isolated fatty
      acids is also present in the CID-MS peaks. In this way, 18 species were found in
      PE1, 43 species were estimated in LCL, and 59 species were ascertained for CL.

PMID- 9171386
TI  - Topology of the outer membrane phospholipase A of Salmonella typhimurium.
AB  - The outer membrane phospholipase A (OMPLA) of Enterobacteriaceae has been
      proposed to span the membrane 14 times as antiparallel amphipathic beta-strands,
      thereby exposing seven loops to the cell surface. We have employed the epitope
      insertion method to probe the topology of OMPLA of Salmonella typhimurium. First,
      missense mutations were introduced at various positions in the pldA gene,
      encoding OMPLA, to create unique BamHI sites. These BamHI sites were subsequently
      used to insert linkers, encoding a 16-amino-acid B-cell epitope. Proper assembly
      of all mutant proteins was revealed by their heat modifiability in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The accessibility of the inserted
      epitopes was assessed. Immunofluorescence analysis of intact cells with
      antibodies against the inserted epitope showed that three of seven predicted
      loops are indeed cell surface exposed. Trypsin accessibility experiments verified
      the cell surface exposure of two additional loops and provided support for the
      proposed periplasmic localization of three predicted turns. For two other
      predicted exposed loops, the results were not conclusive. These results support
      to a large extent the proposed topology model of OMPLA. Furthermore, the
      observation that the substitutions Glu66Pro and Glu247Gly virtually abolished
      enzymatic activity indicates that these residues might play a major role in
      catalysis.

PMID- 9171387
TI  - Isolation and characterization of two genes, waaC (rfaC) and waaF (rfaF),
      involved in Pseudomonas aeruginosa serotype O5 inner-core biosynthesis.
AB  - Recent studies have provided evidence to implicate involvement of the core
      oligosaccharide region of Pseudomonas aeruginosa lipopolysaccharide (LPS) in
      adherence to host tissues. To better understand the role played by LPS in the
      virulence of this organism, the aim of the present study was to clone and
      characterize genes involved in core biosynthesis. The inner-core regions of P.
      aeruginosa and Salmonella enterica serovar Typhimurium are structurally very
      similar; both contain two main chain residues of heptose linked to lipid A-Kdo2
      (Kdo is 3-deoxy-D-manno-octulosonic acid). By electrotransforming a P. aeruginosa
      PAO1 library into Salmonella waaC and waaF (formerly known as rfaC and rfaF,
      respectively) mutants, we were able to isolate the homologous heptosyltransferase
      I and II genes of P. aeruginosa. Two plasmids, pCOREc1 and pCOREc2, which
      restored smooth LPS production in the waaC mutant, were isolated. Similarly,
      plasmid pCOREf1 was able to complement the Salmonella waaF mutant. Sequence
      analysis of the DNA insert of pCOREc2 revealed one open reading frame (ORF) which
      could code for a protein of 39.8 kDa. The amino acid sequence of the deduced
      protein exhibited 53% identity with the sequence of the WaaC protein of S.
      enterica serovar Typhimurium. pCOREf1 contained one ORF capable of encoding a
      38.4-kDa protein. The sequence of the predicted protein was 49% identical to the
      sequence of the Salmonella WaaF protein. Protein expression by the Maxicell
      system confirmed that a 40-kDa protein was encoded by pCOREc2 and a 38-kDa
      protein was encoded by pCOREf1. Pulsed-field gel electrophoresis was used to
      determine the map locations of the cloned waaC and waaF genes, which were found
      to lie between 0.9 and 6.6 min on the PAO1 chromosome. Using a gene-replacement
      strategy, we attempted to generate P. aeruginosa waaC and waaF null mutants.
      Despite multiple attempts to isolate true knockout mutants, all transconjugants
      were identified as merodiploids.

PMID- 9171388
TI  - Maximization of transcription of the serC (pdxF)-aroA multifunctional operon by
      antagonistic effects of the cyclic AMP (cAMP) receptor protein-cAMP complex and
      Lrp global regulators of Escherichia coli K-12.
AB  - The arrangement of the Escherichia coli serC (pdxF) and aroA genes into a
      cotranscribed multifunctional operon allows coregulation of two enzymes required
      for the biosynthesis of L-serine, pyridoxal 5'-phosphate, chorismate, and the
      aromatic amino acids and vitamins. RNase T2 protection assays revealed two major
      transcripts that were initiated from a promoter upstream from serC (pdxF).
      Between 80 to 90% of serC (pdxF) transcripts were present in single-gene mRNA
      molecules that likely arose by Rho-independent termination between serC (pdxF)
      and aroA. serC (pdxF)-aroA cotranscripts terminated at another Rho-independent
      terminator near the end of aroA. We studied operon regulation by determining
      differential rates of beta-galactosidase synthesis in a merodiploid strain
      carrying a single-copy lambda[phi(serC [pdxF]'-lacZYA)] operon fusion. serC
      (pdxF) transcription was greatest in bacteria growing in minimal salts-glucose
      medium (MMGlu) and was reduced in minimal salts-glycerol medium, enriched MMGlu,
      and LB medium. serC (pdxF) transcription was increased in cya or crp mutants
      compared to their cya+ crp+ parent in MMGlu or LB medium. In contrast, serC
      (pdxF) transcription decreased in an lrp mutant compared to its lrp+ parent in
      MMGlu. Conclusions obtained by using the operon fusion were corroborated by
      quantitative Western immunoblotting of SerC (PdxF), which was present at around
      1,800 dimers per cell in bacteria growing in MMGlu. RNase T2 protection assays of
      serC (pdxF)-terminated and serC (pdxF)-aroA cotranscript amounts supported the
      conclusion that the operon was regulated at the transcription level under the
      conditions tested. Results with a series of deletions upstream of the P(serC
      (pdxF)) promoter revealed that activation by Lrp was likely direct, whereas
      repression by the cyclic AMP (cAMP) receptor protein-cAMP complex (CRP-cAMP) was
      likely indirect, possibly via a repressor whose amount or activity was stimulated
      by CRP-cAMP.

PMID- 9171390
TI  - Purification, characterization, and properties of an aryl aldehyde oxidoreductase
      from Nocardia sp. strain NRRL 5646.
AB  - An aryl aldehyde oxidoreductase from Nocardia sp. strain NRRL 5646 was purified
      196-fold by a combination of Mono-Q, Reactive Green 19 agarose affinity, and
      hydroxyapatite chromatographies. The purified enzyme runs as a single band of 140
      kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular
      mass was estimated to be 163 +/- 3.8 kDa by gel filtration, indicating that this
      enzyme is a monomeric protein. The binding of the enzyme to Reactive Green 19
      agarose was Mg2+ dependent. The binding capacity was estimated to be about 0.2 mg
      of Reactive Green agarose per ml in the presence of 10 mM MgCl2. This enzyme can
      catalyze the reduction of a wide range of aryl carboxylic acids, including
      substituted benzoic acids, phenyl-substituted aliphatic acids, heterocyclic
      carboxylic acids, and polyaromatic ring carboxylic acids, to produce the
      corresponding aldehydes. The Km values for benzoate, ATP, and NADPH were
      determined to be 645 +/- 75, 29.3 +/- 3.1, and 57.3 +/- 12.5 microM,
      respectively. The Vmax was determined to be 0.902 +/- 0.04 micromol/min/mg of
      protein. Km values for (S)-(+)-alpha-methyl-4-(2-methylpropyl)-benzeneacetic acid
      (ibuprofen) and its (R)-(-) isomer were determined to be 155 +/- 18 and 34.5 +/-
      2.5 microM, respectively. The Vmax for the (S)-(+) and (R)-(-) isomers were 1.33
      and 0.15 micromol/min/mg of protein, respectively. Anthranilic acid is a
      competitive inhibitor with benzoic acid as a substrate, with a Ki of 261 +/- 30
      microM. The N-terminal and internal amino acid sequences of a 76-kDa peptide from
      limited alpha-chymotrypsin digestion were determined.

PMID- 9171389
TI  - Structure and expression of a pyrimidine gene cluster from the extreme
      thermophile Thermus strain ZO5.
AB  - On a 4.7-kbp HindIII clone of Thermus strain ZO5 DNA, complementing an aspartate
      carbamoyltransferase mutation in Escherichia coli, we identified a cluster of
      four potential open reading frames corresponding to genes pyrR, and pyrB, an
      unidentified open reading frame named bbc, and gene pyrC. The transcription
      initiation site was mapped at about 115 nucleotides upstream of the pyrR
      translation start codon. The cognate Thermus pyr promoter also functions in
      heterologous expression of Thermus pyr genes in E. coli. In Thermus strain ZO5,
      pyrB and pyrC gene expression is repressed three- to fourfold by uracil and
      increased twofold by arginine. Based on the occurrence of several transcription
      signals in the Thermus pyr promoter region and strong amino acid sequence
      identities (about 60%) between Thermus PyrR and the PyrR attenuation proteins of
      two Bacillus sp., we propose a regulatory mechanism involving transcriptional
      attenuation to control pyr gene expression in Thermus. In contrast to pyr
      attenuation in Bacillus spp., however, control of the Thermus pyr gene cluster
      would not involve an antiterminator structure but would involve a translating
      ribosome for preventing formation of the terminator RNA hairpin. The deduced
      amino acid sequence of Thermus strain ZO5 aspartate carbamoyltransferase (ATCase;
      encoded by pyrB) exhibits the highest similarities (about 50% identical amino
      acids) with ATCases from Pseudomonas sp. For Thermus strain ZO5 dihydroorotase
      (DHOase; encoded by pyrC), the highest similarity scores (about 40% identity)
      were obtained with DHOases from B. caldolyticus and Bacillus subtilis. The enzyme
      properties of ATCase expressed from truncated versions of the Thermus pyr gene
      cluster in E. coli suggest that Thermus ATCase is stabilized by DHOase and that
      the translation product of bbc plays a role in feedback inhibition of the ATCase
      DHOase complex.

PMID- 9171391
TI  - The Helicobacter pylori ureC gene codes for a phosphoglucosamine mutase.
AB  - The function of UreC, the product of a 1,335-bp-long open reading frame upstream
      from the urease structural genes (ureAB) of Helicobacter pylori, was
      investigated. We present data showing that the ureC gene product is a
      phosphoglucosamine mutase. D. Mengin-Lecreulx and J. van Heijenoort (J. Biol.
      Chem. 271:32-39, 1996) observed that UreC is similar (43% identity) to the GlmM
      protein of Escherichia coli. Those authors showed that GlmM is a
      phosphoglucosamine mutase catalyzing interconversion of glucosamine-6-phosphate
      into glucosamine-1-phosphate, which is subsequently transformed into UDP-N
      acetylglucosamine. The latter product is one of the main cytoplasmic precursors
      of cell wall peptidoglycan and outer membrane lipopolysaccharides. The present
      paper reports that, like its E. coli homolog glmM, the H. pylori ureC gene is
      essential for cell growth. It was known that growth of a lethal conditional glmM
      mutant of E. coli at a nonpermissive temperature can be restored in the presence
      of the ureC gene. We showed that complete complementation of the glmM mutant can
      be obtained with a plasmid overproducing UreC. The peptidoglycan content and the
      specific phosphoglucosamine mutase activity of such a complemented strain were
      measured; these results demonstrated that the ureC gene product functions as a
      phosphoglucosamine mutase. Homologs of the UreC and GlmM proteins were identified
      in Haemophilus influenzae, Mycobacterium leprae, Clostridium perfringens,
      Synechocystis sp. strain PCC6803, and Methanococcus jannaschii. Significant
      conservation of the amino acid sequence of these proteins in such diverse
      organisms suggests a very ancient common ancestor for the genes and defines a
      consensus motif for the phosphoglucosamine mutase active site. We propose
      renaming the H. pylori ureC gene the glmM gene.

PMID- 9171392
TI  - The Escherichia coli histone-like protein HU affects DNA initiation, chromosome
      partitioning via MukB, and cell division via MinCDE.
AB  - Escherichia coli hupA hupB double mutants, lacking both subunits (HU1 and HU2) of
      the histone-like protein HU, accumulate secondary mutations. In some genetic
      backgrounds, these include mutations in the minCDE operon, inactivating this
      system of septation control and resulting in the formation of minicells. In the
      course of the characterization of hupA hupB mutants, we observed that the
      simultaneous absence of the HU2 subunit and the MukB protein, implicated in
      chromosome partitioning, is lethal for the bacteria; the integrity of either HU
      or MukB thus seems to be essential for bacterial growth. The HU protein has been
      shown to be involved in DNA replication in vitro; we show here that its
      inactivation in the hupA hupB double mutant disturbs the synchrony of replication
      initiation in vivo, as evaluated by flow cytometry. Our results suggest that
      global nucleoid structure, determined in part by the histone-like protein HU,
      plays a role in DNA replication initiation, in proper chromosome partitioning
      directed by the MukFEB proteins, and in correct septum placement directed by the
      MinCDE proteins.

PMID- 9171393
TI  - The cyclic AMP receptor protein is the main activator of pectinolysis genes in
      Erwinia chrysanthemi.
AB  - The main virulence factors of the phytopathogenic bacterium Erwinia chrysanthemi
      are pectinases that cleave pectin, a major constituent of the plant cell wall.
      Although physiological studies suggested that pectinase production in Erwinia
      species is subjected to catabolite repression, the direct implication of the
      cyclic AMP receptor protein (CRP) in this regulation has never been demonstrated.
      To investigate the role of CRP in pectin catabolism, we cloned the E.
      chrysanthemi crp gene by complementation of an Escherichia coli crp mutation and
      then constructed E. chrysanthemi crp mutants by reverse genetics. The
      carbohydrate fermentation phenotype of the E. chrysanthemi crp mutants is similar
      to that of an E. coli crp mutant. Furthermore, these mutants are unable to grow
      on pectin or polygalacturonate as the sole carbon source. Analysis of the
      nucleotide sequence of the E. chrysanthemi crp gene revealed the presence of a
      630-bp open reading frame (ORF) that codes for a protein highly similar to the
      CRP of E. coli. Using a crp::uidA transcriptional fusion, we demonstrated that
      the E. chrysanthemi CRP represses its own expression, probably via a mechanism
      similar to that described for the E. coli crp gene. Moreover, in the E.
      chrysanthemi crp mutants, expression of pectinase genes (pemA, pelB, pelC, pelD,
      and pelE) and of genes of the intracellular part of the pectin degradation
      pathway (ogl, kduI, and kdgT), which are important for inducer formation and
      transport, is dramatically reduced in induced conditions. In contrast, expression
      of pelA, which encodes a pectate lyase important for E. chrysanthemi
      pathogenicity, seems to be negatively regulated by CRP. The E. chrysanthemi crp
      mutants have greatly decreased maceration capacity in potato tubers, chicory
      leaves, and celery petioles as well as highly diminished virulence on saintpaulia
      plants. These findings demonstrate that CRP plays a crucial role in expression of
      the pectinolysis genes and in the pathogenicity of E. chrysanthemi.

PMID- 9171394
TI  - Determination of DNA sequences required for regulated Mycobacterium tuberculosis
      RecA expression in response to DNA-damaging agents suggests that two modes of
      regulation exist.
AB  - The recA gene of Mycobacterium tuberculosis has previously been cloned and
      sequenced (E. O. Davis, S. G. Sedgwick, and M. J. Colston, J. Bacteriol. 173:5653
      5662, 1991). In this study, the expression of this gene was shown to be inducible
      in response to various DNA-damaging agents by using a transcriptional fusion to
      the reporter gene encoding chloramphenicol acetyltransferase. A segment of DNA
      around 300 bp upstream of the coding region was shown to be required for
      expression. However, primer extension analysis indicated that the transcriptional
      start sites were 47 and 93 bp upstream of the translation initiation codon.
      Sequence motifs with homology to two families of Escherichia coli promoters but
      also with significant differences were located near these proposed transcription
      start sites. The differences from the E. coli consensus patterns would explain
      the previously described lack of expression of the M. tuberculosis recA gene from
      its own promoter in E. coli. In addition, the M. tuberculosis LexA protein was
      shown to bind specifically to a sequence, GAAC-N4-GTTC, overlapping one of these
      putative promoters and homologous to the Bacillus subtilis Cheo box involved in
      the regulation of SOS genes. The region of DNA 300 bp upstream of the recA gene
      was shown not to contain a promoter, suggesting that it functions as an upstream
      activator sequence.

PMID- 9171395
TI  - Enhancing transcription through the Escherichia coli hemolysin operon, hlyCABD:
      RfaH and upstream JUMPStart DNA sequences function together via a postinitiation
      mechanism.
AB  - Escherichia coli hlyCABD operons encode the polypeptide component (HlyA) of an
      extracellular cytolytic toxin as well as proteins required for its acylation
      (HlyC) and sec-independent secretion (HlyBD). The E. coli protein RfaH is
      required for wild-type hemolysin expression at the level of hlyCABD transcript
      elongation (J. A. Leeds and R. A. Welch, J. Bacteriol. 178:1850-1857, 1996). RfaH
      is also required for the transcription of wild-type levels of mRNA from promoter
      distal genes in the rfaQ-K, traY-Z, and rplK-rpoC gene clusters, supporting the
      role for RfaH in transcriptional elongation. All or portions of a common 39-bp
      sequence termed JUMPStart are present in the untranslated regions of RfaH
      enhanced operons. In this study, we tested the model that the JUMPStart sequence
      and RfaH are part of the same functional pathway. We examined the effect of
      JUMPStart deletion mutations within the untranslated leader of a chromosomally
      derived hlyCABD operon on hly RNA and HlyA protein levels in either wild-type or
      rfaH null mutant E. coli. We also provide in vivo physical evidence that is
      consistent with RNA polymerase pausing at the wild-type JUMPStart sequences.

PMID- 9171396
TI  - In vivo supercoiling of plasmid and chromosomal DNA in an Escherichia coli hns
      mutant.
AB  - We have used trimethylpsoralen to measure localized levels of unconstrained DNA
      supercoiling in vivo. The data provide direct evidence that plasmid and
      chromosomal DNA supercoiling is altered in vivo in an hns mutant. This increase
      in supercoiling is independent of transcription or changes in the activity of
      topoisomerase I. These data have implications for the mechanisms by which the
      chromatin-associated protein H-NS may influence chromosome organization and gene
      expression.

PMID- 9171397
TI  - Characterization of the nitric oxide reductase-encoding region in Rhodobacter
      sphaeroides 2.4.3.
AB  - A gene cluster which includes genes required for the expression of nitric oxide
      reductase in Rhodobacter sphaeroides 2.4.3 has been isolated and characterized.
      Sequence analysis indicates that the two proximal genes in the cluster are the
      Nor structural genes. These two genes and four distal genes apparently constitute
      an operon. Mutational analysis indicates that the two structural genes, norC and
      norB, and the genes immediately downstream, norQ and norD, are required for
      expression of an active Nor complex. The remaining two genes, nnrT and nnrU, are
      required for expression of both Nir and Nor. The products of norCBQD have
      significant identity with products from other denitrifiers, whereas the predicted
      nnrT and nnrU gene products have no similarity with products corresponding to
      other sequences in the database. Mutational analysis and functional
      complementation studies indicate that the nnrT and nnrU genes can be expressed
      from an internal promoter. Deletion analysis of the regulatory region upstream of
      norC indicated that a sequence motif which has identity to a motif in the gene
      encoding nitrite reductase in strain 2.4.3 is critical for nor operon expression.
      Regulatory studies demonstrated that the first four genes, norCBQD, are expressed
      only when the oxygen concentration is low and nitrate is present but that the two
      distal genes, nnrTU, are expressed constitutively.

PMID- 9171399
TI  - 2-oxo-1,2-dihydroquinoline 8-monooxygenase: phylogenetic relationship to other
      multicomponent nonheme iron oxygenases.
AB  - 2-Oxo-1,2-dihydroquinoline 8-monooxygenase, an enzyme involved in quinoline
      degradation by Pseudomonas putida 86, had been identified as a class IB two
      component nonheme iron oxygenase based on its biochemical and biophysical
      properties (B. Rosche, B. Tshisuaka, S. Fetzner, and F. Lingens, J. Biol. Chem.
      270:17836-17842, 1995). The genes oxoR and oxoO, encoding the reductase and the
      oxygenase components of the enzyme, were sequenced and analyzed. oxoR was
      localized approximately 15 kb downstream of oxoO. Expression of both genes was
      detected in a recombinant Pseudomonas strain. In the deduced amino acid sequence
      of the NADH:(acceptor) reductase component (OxoR, 342 amino acids), putative
      binding sites for a chloroplast-type [2Fe-2S] center, for flavin adenine
      dinucleotide, and for NAD were identified. The arrangement of these cofactor
      binding sites is conserved in all known class IB reductases. A dendrogram of
      reductases confirmed the similarity of OxoR to other class IB reductases. The
      oxygenase component (OxoO, 446 amino acids) harbors the conserved amino acid
      motifs proposed to bind the Rieske-type [2Fe-2S] cluster and the mononuclear
      iron. In contrast to known class IB oxygenase components, which are composed of
      differing subunits, OxoO is a homomultimer, which is typical for class IA
      oxygenases. Sequence comparison of oxygenases indeed revealed that OxoO is more
      related to class IA than to class IB oxygenases. Thus, 2-oxo-1,2-dihydroquinoline
      8-monooxygenase consists of a class IB-like reductase and a class IA-like
      oxygenase. These results support the hypothesis that multicomponent enzymes may
      be composed of modular elements having different phylogenetic origins.

PMID- 9171398
TI  - Porin polypeptide contributes to surface charge of gonococci.
AB  - Each strain of Neisseria gonorrhoeae elaborates a single porin polypeptide, with
      the porins expressed by different strains comprising two general classes, Por1A
      and Por1B. In the outer membrane, each porin molecule folds into 16 membrane
      spanning beta-strands joined by top- and bottom-loop domains. Por1A and Por1B
      have similar membrane-spanning regions, but the eight surface-exposed top loops
      (I to VIII) differ in length and sequence. To determine whether porins, and
      especially their top loop domains, contribute to bacterial cell surface charge,
      strain MS11 gonococci that were identical except for expressing a recombinant
      Por1A, Por1B, or mosaic Por1A-1B polypeptide were compared by whole-cell
      electrophoresis. These porin variants displayed different electrophoretic
      mobilities that correlated with the net numbers of charged amino acids within
      surface-exposed loops of their respective porin polypeptides. The
      susceptibilities of porin variants to polyanionic sulfated polymers correlated
      roughly with gonococcal surface charge; those porin variants with diminished
      surface negativity showed increased sensitivity to the polyanionic sulfated
      compounds. These observations indicate that porin polypeptides in situ contribute
      to the surface charge of gonococci, and they suggest that the bacterium's
      interactions with large sulfated compounds are thereby affected.

PMID- 9171400
TI  - L-allo-threonine aldolase from Aeromonas jandaei DK-39: gene cloning, nucleotide
      sequencing, and identification of the pyridoxal 5'-phosphate-binding lysine
      residue by site-directed mutagenesis.
AB  - We have isolated the gene encoding L-allo-threonine aldolase (L-allo-TA) from
      Aeromonas jandaei DK-39, a pyridoxal 5'-phosphate (PLP)-dependent enzyme that
      stereospecifically catalyzes the interconversion of L-allo-threonine and glycine.
      The gene contains an open reading frame consisting of 1,014 nucleotides
      corresponding to 338 amino acid residues. The protein molecular weight was
      estimated to be 36,294, which is in good agreement with the subunit molecular
      weight of the enzyme determined by polyacrylamide gel electrophoresis. The enzyme
      was overexpressed in recombinant Escherichia coli cells and purified to
      homogeneity by one hydrophobic column chromatography step. The predicted amino
      acid sequence showed no significant similarity to those of the currently known
      PLP-dependent enzymes but displayed 40 and 41% identity with those of the
      hypothetical GLY1 protein of Saccharomyces cerevisiae and the GLY1-like protein
      of Caenorhabditis elegans, respectively. Accordingly, L-allo-TA might represent a
      new type of PLP-dependent enzyme. To determine the PLP-binding site of the
      enzyme, all of the three conserved lysine residues of L-allo-TA were replaced by
      alanine by site-directed mutagenesis. The purified mutant enzymes, K51A and
      K224A, showed properties similar to those of the wild type, while the mutant
      enzyme K199A was catalytically inactive, with corresponding disappearance of the
      absorption maximum at 420 nm. Thus, Lys199 of L-allo-TA probably functions as an
      essential catalytic residue forming an internal Schiff base with PLP of the
      enzyme to catalyze the reversible aldol reaction.

PMID- 9171401
TI  - Sequences and expression of pyruvate dehydrogenase genes from Pseudomonas
      aeruginosa.
AB  - A mutant of Pseudomonas aeruginosa, OT2100, which appeared to be defective in the
      production of the fluorescent yellow-green siderophore pyoverdine had been
      isolated previously following transposon mutagenesis (T. R. Merriman and I. L.
      Lamont, Gene 126:17-23, 1993). DNA from either side of the transposon insertion
      site was cloned, and the sequence was determined. The mutated gene had strong
      identity with the dihydrolipoamide acetyltransferase (E2) components of pyruvate
      dehydrogenase (PDH) from other bacterial species. Enzyme assays revealed that the
      mutant was defective in the E2 subunit of PDH, preventing assembly of a
      functional complex. PDH activity in OT2100 cell extracts was restored when
      extract from an E1 mutant was added. On the basis of this evidence, OT2100 was
      identified as an aceB or E2 mutant. A second gene, aceA, which is likely to
      encode the E1 component of PDH, was identified upstream from aceB.
      Transcriptional analysis revealed that aceA and aceB are expressed as a 5-kb
      polycistronic transcript from a promoter upstream of aceA. An intergenic region
      of 146 bp was located between aceA and aceB, and a 2-kb aceB transcript that
      originated from a promoter in the intergenic region was identified. DNA fragments
      upstream of aceA and aceB were shown to have promoter activities in P.
      aeruginosa, although only the aceA promoter was active in Escherichia coli. It is
      likely that the apparent pyoverdine-deficient phenotype of mutant OT2100 is a
      consequence of acidification of the growth medium due to accumulation of pyruvic
      acid in the absence of functional PDH.

PMID- 9171402
TI  - A new type of hemophore-dependent heme acquisition system of Serratia marcescens
      reconstituted in Escherichia coli.
AB  - The utilization by Serratia marcescens of heme bound to hemoglobin requires HasA,
      an extracellular heme-binding protein. This unique heme acquisition system was
      studied in an Escherichia coli hemA mutant that was a heme auxotroph. We
      identified a 92-kDa iron-regulated S. marcescens outer membrane protein, HasR,
      which alone enabled the E. coli hemA mutant to grow on heme or hemoglobin as a
      porphyrin source. The concomitant secretion of HasA by the HasR-producing hemA
      mutant greatly facilitates the acquisition of heme from hemoglobin. This is the
      first report of a synergy between an outer membrane protein and an extracellular
      heme-binding protein, HasA, acting as a heme carrier, which we termed a
      hemophore.

PMID- 9171403
TI  - Characterization of Azorhizobium caulinodans glnB and glnA genes: involvement of
      the P(II) protein in symbiotic nitrogen fixation.
AB  - The nucleotide sequence and transcriptional organization of Azorhizobium
      caulinodans ORS571 glnA, the structural gene for glutamine synthetase (GS), and
      glnB, the structural gene for the P(II) protein, have been determined. glnB and
      glnA are organized as a single operon transcribed from the same start site, under
      conditions of both nitrogen limitation and nitrogen excess. This start site may
      be used by two different promoters since the expression of a glnB-lacZ fusion was
      high in the presence of ammonia and enhanced under conditions of nitrogen
      limitation in the wild-type strain. The increase was not observed in rpoN or ntrC
      mutants. In addition, this fusion was overexpressed under both growth conditions,
      in the glnB mutant strain, suggesting that P(II) negatively regulates its own
      expression. A DNA motif, similar to a sigma54-dependent promoter consensus, was
      found in the 5' nontranscribed region. Thus, the glnBA operon seems to be
      transcribed from a sigma54-dependent promoter that operates under conditions of
      nitrogen limitation and from another uncharacterized promoter in the presence of
      ammonia. Both glnB and glnBA mutant strains derepress their nitrogenase in the
      free-living state, but only the glnBA mutant, auxotrophic for glutamine, does not
      utilize molecular nitrogen for growth. The level of GS adenylylation is not
      affected in the glnB mutant as compared to that in the wild type. Under symbiotic
      conditions, the glnB and glnBA mutant strains induced Fix- nodules on Sesbania
      rostrata roots. P(II) is the first example in A. caulinodans of a protein
      required for symbiotic nitrogen fixation but dispensable in bacteria growing in
      the free-living state.

PMID- 9171404
TI  - Isolation and characterization of multiple adenylate cyclase genes from the
      cyanobacterium Anabaena sp. strain PCC 7120.
AB  - Adenylate cyclase genes, designated cyaA, cyaB1, cyaB2, cyaC, and cyaD, were
      isolated from the filamentous cyanobacterium Anabaena sp. strain PCC 7120 by
      complementation of a strain of Escherichia coli defective for the presence of
      cya. These genes encoded polypeptides consisting of 735, 859, 860, 1,155, and 546
      amino acid residues, respectively. Deduced amino acid sequences of the regions
      near the C-terminal ends of these cya genes were similar to those of catalytic
      domains of eukaryotic adenylate cyclases. The remaining part of each cya gene
      towards its N-terminal end showed a characteristic structure. CyaA had two
      putative membrane-spanning regions. Both CyaB1 and CyaB2 had regions that were
      very similar to the cyclic GMP (cGMP)-binding domain of cGMP-stimulated cGMP
      phosphodiesterase. CyaC consisted of four distinct domains forming sequentially
      from the N terminus: a response regulator-like domain, a histidine kinase-like
      domain, a response regulator-like domain, and the catalytic domain of adenylate
      cyclase. CyaD contained the forkhead-associated domain in its N-terminal region.
      Expression of these genes was examined by reverse transcription-PCR. The
      transcript of cyaC was shown to be predominant in this cyanobacterium. The
      cellular cyclic AMP level in the disruptant of the cyaC mutant was much lower
      than that in the wild type.

PMID- 9171405
TI  - The plasmid R64 thin pilus identified as a type IV pilus.
AB  - The entire nucleotide sequence of the pil region of the IncI1 plasmid R64 was
      determined. Analysis of the sequence indicated that 14 genes, designated pilI
      through pilV, are involved in the formation of the R64 thin pilus. Protein
      products of eight pil genes were identified by the maxicell procedure. The pilN
      product was shown to be a lipoprotein by an experiment using globomycin. A
      computer search revealed that several R64 pil genes have amino acid sequence
      homology with proteins involved in type IV pilus biogenesis, protein secretion,
      and transformation competence. The pilS and pilV products were suggested to be
      prepilins for the R64 thin pilus, and the pilU product appears to be a prepilin
      peptidase. These results suggest that the R64 thin pilus belongs to the type IV
      family, specifically group IVB, of pili. The requirement of the pilR and pilU
      genes for R64 liquid mating was demonstrated by constructing their frameshift
      mutations. Comparison of three type IVB pilus biogenesis systems, the pil system
      of R64, the toxin-coregulated pilus (tcp) system of Vibrio cholerae, and the
      bundle-forming pilus (bfp) system of enteropathogenic Escherichia coli, suggests
      that they have evolved from a common ancestral gene system.

PMID- 9171406
TI  - Specific detection of Salmonella typhimurium proteins synthesized
      intracellularly.
AB  - Studies of the proteins Salmonella typhimurium synthesizes under conditions
      designed to more closely approximate the in vivo environment, i.e., in cell and
      tissue culture, are not easily interpreted because they have involved chemical
      inhibition of host cell protein synthesis during infection. The method which we
      have developed allows specific labeling of bacterial proteins without interfering
      with host cell metabolic activities by using a labeled lysine precursor which
      mammalian cells cannot utilize. We have resolved the labeled proteins using two
      dimensional electrophoresis and autofluorography. We were able to detect 57
      proteins synthesized by S. typhimurium during growth within a human intestinal
      epithelial cell line. Of the 57 proteins detected, 34 appear to be unique to the
      intracellular environment, i.e., they are not seen during growth of the bacteria
      in tissue culture medium alone. Current (and future) efforts are directed at
      organizing the 34 proteins into known stress response groups, determining the
      cellular locations of the proteins (outer or inner membrane, etc.), and comparing
      the pattern of proteins synthesized within an intestinal epithelial cell to the
      pattern synthesized during growth within other tissues.

PMID- 9171407
TI  - Overexpression and characterization of a prolyl endopeptidase from the
      hyperthermophilic archaeon Pyrococcus furiosus.
AB  - The maltose-regulated mlr-2 gene from the hyperthermophilic archaeon Pyrococcus
      furiosus having homology to bacterial and eukaryal prolyl endopeptidase (PEPase)
      was cloned and overexpressed in Escherichia coli. Extracts from recombinant cells
      were capable of hydrolyzing the PEPase substrate benzyloxycarbonyl-Gly-Pro-p
      nitroanilide (ZGPpNA) with a temperature optimum between 85 and 90 degrees C.
      Denaturing gel electrophoresis of purified PEPase showed that enzyme activity was
      associated with a 70-kDa protein, which is consistent with that predicted from
      the mlr-2 sequence. However, an apparent molecular mass of 59 kDa was obtained
      from gel permeation studies. In addition to ZGPpNA (K(Mapp) of 53 microM), PEPase
      was capable of hydrolyzing azocasein, although at a low rate. No activity was
      detected when ZGPpNA was replaced by substrates for carboxypeptidase A and B,
      chymotrypsin, subtilisin, and neutral endopeptidase. N-[N-(L-3-trans-Carboxirane
      2-carbonyl)-L-Leu]-agmatine (E-64) and tosyl-L-Lys chloromethyl ketone did not
      inhibit PEPase activity. Both phenylmethylsulfonyl fluoride and diprotin A
      inhibited ZGPpNA cleavage, the latter doing so competitively (K(lapp) of 343
      microM). At 100 degrees C, the enzyme displayed some tolerance to sodium dodecyl
      sulfate treatment. Stability of PEPase over time was dependent on protein
      concentration; at temperatures above 65 degrees C, dilute samples retained most
      of their activity after 24 h while the activity of concentrated preparations
      diminished significantly. This decrease was found to be due, in part, to
      autoproteolysis. Partially purified PEPase from P. furiosus exhibited the same
      temperature optimum, molecular weight, and kinetic characteristics as the enzyme
      overexpressed in E. coli. Extracts from P. furiosus cultures grown in the
      presence of maltose were approximately sevenfold greater in PEPase activity than
      those grown without maltose. Activity could not be detected in clarified medium
      obtained from maltose-grown cultures. We conclude that mlr-2, now called prpA,
      encodes PEPase; the physiological role of this protease is presently unknown.

PMID- 9171408
TI  - Growth phase-dependent transcription of the Streptomyces ramocissimus tuf1 gene
      occurs from two promoters.
AB  - The str operon of Streptomyces ramocissimus contains the genes for ribosomal
      proteins S12 (rpsL) and S7 (rpsG) and for the polypeptide chain elongation
      factors G (EF-G) (fus) and Tu (EF-Tu) (tuf). This kirromycin producer contains
      three tuf or tuf-like genes; tuf1 encodes the regular EF-Tu and is located
      immediately downstream of fus. In vivo and in vitro transcription analysis
      revealed a transcription start site directly upstream of S. ramocissimus tuf1, in
      addition to the operon promoter rpsLp. Transcription from these promoters
      appeared to be growth phase dependent, diminishing drastically upon entry into
      stationary phase and at the onset of production of the EF-Tu-targeted antibiotic
      kirromycin. In surface-grown cultures, a second round of tuf1 transcription,
      coinciding with aerial mycelium formation and kirromycin production, was
      observed. The tuf1-specific promoter (tuf1p) was located in the intercistronic
      region between fus and tuf1 by high-resolution S1 mapping, in vitro
      transcription, and in vivo promoter probing. During logarithmic growth, the tuf1p
      and rpsLp transcripts are present at comparable levels. In contrast to
      Escherichia coli, which has two almost identical tuf genes, the gram-positive S.
      ramocissimus contains only tuf1 for its regular EF-Tu. High levels of EF-Tu may
      therefore be achieved by the compensatory activity of tuf1p.

PMID- 9171409
TI  - Molecular cloning, sequencing, and expression of lytM, a unique autolytic gene of
      Staphylococcus aureus.
AB  - A gene encoding an autolytic activity was identified in an autolysis-deficient
      mutant (Lyt-) of Staphylococcus aureus which produces only a single band in
      autolytic-activity gels (N. Mani, P. Tobin, and R. K. Jayaswal, J. Bacteriol.
      175:1493-1499, 1993). An open reading frame, designated lytM, of 948 bp that
      could encode a polypeptide of 316 amino acid residues was identified. The
      calculated molecular mass of the lytM gene product (34.4 kDa) corresponded to
      that of the autolytic activity detected (approximately 36 kDa) in the Lyt-
      mutant. Results deduced from amino acid sequence analysis and N-terminal amino
      acid sequencing data suggest that LytM is a secreted protein. The C-terminal
      region of the putative protein encoded by lytM showed 51% identity with the N
      terminal region of the mature lysostaphin from Staphylococcus simulans and 50%
      identity with the N-terminal region of ALE-1 from Staphylococcus capitis EPK1.
      Northern blot analysis showed that lytM expresses a transcript of approximately
      955 bp, as predicted from the DNA sequence. Escherichia coli clones carrying the
      lytM gene exhibited autolytic-activity bands of approximately 36 kDa as well as
      of 19 and 22 kDa in activity gels. The lytM gene was mapped to the SmaI-D
      fragment on the S. aureus chromosome. Mapping data and results of hybridization
      experiments with primers generated from gene sequences of known autolytic genes
      of S. aureus clearly indicate that the lytM gene is distinct from other
      staphylococcal autolytic genes reported to date.

PMID- 9171410
TI  - 3-hydroxy-3-methylglutaryl coenzyme A reductase of Sulfolobus solfataricus: DNA
      sequence, phylogeny, expression in Escherichia coli of the hmgA gene, and
      purification and kinetic characterization of the gene product.
AB  - The gene (hmgA) for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC
      1.1.1.34) from the thermophilic archaeon Sulfolobus solfataricus P2 was cloned
      and sequenced. S. solfataricus HMG-CoA reductase exhibited a high degree of
      sequence identity (47%) to the HMG-CoA reductase of the halophilic archaeon
      Haloferax volcanii. Phylogenetic analyses of HMG-CoA reductase protein sequences
      suggested that the two archaeal genes are distant homologs of eukaryotic genes.
      The only known bacterial HMG-CoA reductase, a strictly biodegradative enzyme from
      Pseudomonas mevalonii, is highly diverged from archaeal and eukaryotic HMG-CoA
      reductases. The S. solfataricus hmgA gene encodes a true biosynthetic HMG-CoA
      reductase. Expression of hmgA in Escherichia coli generated a protein that both
      converted HMG-CoA to mevalonate and cross-reacted with antibodies raised against
      rat liver HMG-CoA reductase. S. solfataricus HMG-CoA reductase was purified in
      40% yield to a specific activity of 17.5 microU per mg at 50 degrees C by a
      sequence of steps that included heat treatment, ion-exchange chromatography,
      hydrophobic interaction chromatography, and affinity chromatography. The final
      product was homogeneous, as judged by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The substrate was (S)- not (R)-HMG-CoA; the reductant was NADPH
      not NADH. The Km values for HMG-CoA (17 microM) and NADPH (23 microM) were
      similar in magnitude to those of other biosynthetic HMG-CoA reductases. Unlike
      other HMG-CoA reductases, the enzyme was stable at 90 degrees C and was optimally
      active at pH 5.5 and 85 degrees C.

PMID- 9171411
TI  - A two-component system in Ralstonia (Pseudomonas) solanacearum modulates
      production of PhcA-regulated virulence factors in response to 3-hydroxypalmitic
      acid methyl ester.
AB  - Expression of virulence factors in Ralstonia solanacearum is controlled by a
      complex regulatory network, at the center of which is PhcA, a LysR family
      transcriptional regulator. We report here that expression of phcA and production
      of PhcA-regulated virulence factors are affected by products of the putative
      operon phcBSR(Q). phcB is required for production of an extracellular factor
      (EF), tentatively identified as the fatty acid derivative 3-hydroxypalmitic acid
      methyl ester (3-OH PAME), but a biochemical function for PhcB could not be
      deduced from DNA sequence analysis. The other genes in the putative operon are
      predicted to encode proteins homologous to members of two-component signal
      transduction systems: PhcS has amino acid similarity to histidine kinase sensors,
      whereas PhcR and OrfQ are similar to response regulators. PhcR is quite unusual
      because its putative output domain strongly resembles the histidine kinase domain
      of a sensor protein. Production of the PhcA-regulated factors exopolysaccharide
      I, endoglucanase, and pectin methyl esterase was reduced 10- to 100-fold only in
      mutants with a nonpolar insertion in phcB [which express phcSR(Q) in the absence
      of the EF]; simultaneously, expression of phcA was reduced fivefold. Both a wild
      type phenotype and phcA expression were restored by addition of 3-OH PAME to
      growing cultures. Mutants with polar insertions in phcB or lacking the entire
      phcBSR(Q) region produced wild-type levels of PhcA-regulated virulence factors.
      The genetic data suggest that PhcS and PhcR function together to regulate
      expression of phcA, but the biochemical mechanism for this is unclear. At low
      levels of the EF, it is likely that PhcS phosphorylates PhcR, and then PhcR
      interacts either with PhcA (which is required for full expression of phcA) or an
      unknown component of the signal cascade to inhibit expression of phcA. When the
      EF reaches a threshold concentration, we suggest that it reduces the ability of
      PhcS to phosphorylate PhcR, resulting in increased expression of phcA and
      production of PhcA-regulated factors.

PMID- 9171412
TI  - Stimulatory effect of trehalose on formation and activity of Escherichia coli RNA
      polymerase E sigma38 holoenzyme.
AB  - The intracellular concentration of trehalose increases in the stationary-phase
      cells of Escherichia coli. The effects of trehalose on transcription in vitro by
      E. coli RNA polymerase were compared for two holoenzymes, E sigma70 and E
      sigma38, which were reconstituted from purified core enzyme and either sigma70
      (the major sigma at the exponential growth phase) or sigma38 (the essential sigma
      at the stationary growth phase), respectively. The optimum trehalose
      concentration giving maximum transcription by E sigma38 was higher than that by E
      sigma70. Transcription activation by trehalose was attributed to both increased
      formation of E sigma38 holoenzyme and increased transcription initiation by E
      sigma38 from sigma38-dependent promoters. The activation of E sigma38 by
      trehalose was additive with the transcription enhancement by decreased
      superhelicity of template DNA prepared from stationary-phase cells. We thus
      propose that the selective activation of transcription by E sigma38 holoenzyme
      takes place in the presence of specific conditions and factors present under
      stress conditions.

PMID- 9171413
TI  - 2-chloromuconate and ClcR-mediated activation of the clcABD operon: in vitro
      transcriptional and DNase I footprint analyses.
AB  - In Pseudomonas putida, the plasmid-borne clcABD operon encodes enzymes involved
      in 3-chlorocatechol degradation. Previous studies have demonstrated that these
      enzymes are induced when P. putida is grown in the presence of 3-chlorobenzoate,
      which is converted to 3-chlorocatechol, and that ClcR, a LysR-type regulator, is
      required for this induction. The clcABD operon is believed to have evolved from
      the chromosomal catBCA operon, which encodes enzymes that utilize catechol and is
      regulated by CatR. The inducer for the catBCA operon is an intermediate of the
      catechol pathway, cis,cis-muconate. In this study, we demonstrate by the use of
      in vitro transcription assays and lacZ transcription fusions in vivo that the
      analogous intermediate of the 3-chlorocatechol pathway, 2-chloromuconate, is the
      inducer of the clcABD operon. The DNase I footprints of ClcR with and without 2
      chloromuconate were also determined. An extended region of the promoter from -79
      to -25 was occupied in the absence of inducer, but the -35 region was
      unprotected. When 2-chloromuconate was added to the binding assays, the footprint
      contracted approximately 4 bp at the proximal end of the promoter, and the -35
      region was contacted. It is interesting to note that CatR actually extends its
      footprint 14 bp on the catBCA promoter in response to its inducer. Although CatR
      and ClcR change their nucleotide protection patterns in different manners when
      exposed to their respective inducers, their final footprints resemble each other.
      Therefore, it is possible that their transcriptional activation mechanisms may be
      evolutionarily conserved.

PMID- 9171414
TI  - Characterization of Methanobacterium thermoautotrophicum Marburg mutants
      defective in regulation of L-tryptophan biosynthesis.
AB  - Three nitrosoguanidine-induced mutants of the archaeon Methanobacterium
      thermoautotrophicum Marburg resistant to 5-methyltryptophan were isolated and
      characterized. They were found to take up L-tryptophan, as wild-type cells, via
      an energy-dependent, low-affinity transport system specific for L-tryptophan,
      with a Km of 300 microM and a Vmax of 7 nmol/mg (dry weight)/min. Resistance to 5
      methyltryptophan was not due to feedback-resistant anthranilate synthase but to
      constitutive expression of the trp genes, as measured by the specific activities
      of anthranilate synthase and tryptophan synthase, the enzymes encoded by trpEG
      and trpB, respectively, of the trpEGCFBAD gene cluster. Estimation of trpE mRNA
      obtained from mutant cells grown in minimal medium with or without L-tryptophan
      suggested that constitutive expression resulted from deficient transcriptional
      regulation. The enhanced expression of the trp genes in the mutants was found to
      result in intracellular L-tryptophan pools that were two- to fourfold higher than
      in the wild type. Sequencing of the region upstream of trpE revealed in two
      mutants point mutations mapping on the 5'-side of the archaeal box A, whereas in
      the third mutant this region did not differ from that of the wild type. These
      results suggest that (i) in M. thermoautotrophicum the 5-methyltryptophan
      resistant phenotype arises from lesions in components of a regulatory system
      controlling transcription of the trp genes and (ii) cis-acting sequence elements
      in front of the trpE promoter may form part of this system.

PMID- 9171415
TI  - Plasmid maintenance functions of the large virulence plasmid of Shigella
      flexneri.
AB  - The large virulence plasmid pMYSH6000 of Shigella flexneri contains a replicon
      and a plasmid maintenance stability determinant (Stb) on adjacent SalI fragments.
      The presence of a RepFIIA replicon on the SalI C fragment was confirmed, and the
      complete sequence of the adjacent SalI O fragment was determined. It shows
      homology to part of the transfer (tra) operon of the F plasmid. Stb stabilizes a
      partition-defective P1 miniplasmid in Escherichia coli. A 1.1-kb region
      containing a homolog of the F trbH gene was sufficient to confer stability.
      However, the trbH open reading frame could be interrupted without impairing
      stability. Deletion analysis implicated the involvement of two small open reading
      frames, STBORF1 and STBORF2, that fully overlap trbH in the opposite direction.
      These open reading frames are closely related to the vagC and vagD genes of the
      Salmonella dublin virulence plasmid and to open reading frame pairs in the F trbH
      region and in the chromosomes of Dichelobacter nodosus and Haemophilus
      influenzae. Stb appears to promote better-than-random distribution of plasmid
      copies and is a plasmid incompatibility determinant. The F homolog does not
      itself confer stability but exerts incompatibility against the activity of the
      Stb system. Stb is likely to encode either an active partition system or a
      postsegregational killing system. It shows little similarity to previously
      studied plasmid stability loci, but the genetic organization of STBORF1 and
      STBORF2 resembles that of postsegregational killing mechanisms.

PMID- 9171416
TI  - Roles of HoxX and HoxA in biosynthesis of hydrogenase in Bradyrhizobium
      japonicum.
AB  - In-frame deletion mutagenesis was used to study the roles of two Bradyrhizobium
      japonicum proteins, HoxX and HoxA, in hydrogenase biosynthesis; based on their
      sequences, these proteins were previously proposed to be sensor and regulator
      proteins, respectively, of a two-component regulatory system necessary for
      hydrogenase transcription. Deletion of the hoxX gene resulted in a strain that
      expressed only 30 to 40% of wild-type hydrogenase activity. The inactive
      unprocessed form of the hydrogenase large subunit accumulated in this strain,
      indicating a role for HoxX in posttranslational processing of the hydrogenase
      enzyme but not in transcriptional regulation. Strains containing a deletion of
      the hoxA gene or a double mutation (hoxX and hoxA) did not exhibit any
      hydrogenase activity under free-living conditions, and extracts from these
      strains were inactive in gel retardation assays with a 158-bp fragment of the DNA
      region upstream of the hupSL operon. However, bacteroids from root nodules formed
      by all three mutant types (hoxX, hoxA, and hoxX hoxA) exhibited hydrogenase
      activity comparable to that of wild-type bacteroids. Bacteroid extracts from all
      of these strains, including the wild type, failed to cause a shift of the
      hydrogenase upstream region used in our assay. It was shown that HoxA is a DNA
      binding transcriptional activator of hydrogenase structural gene expression under
      free-living conditions but not under symbiotic conditions. Although symbiotic
      hydrogenase expression is still sigma54 dependent, a transcriptional activator
      other than HoxA functions presumably upstream of the HoxA binding site.

PMID- 9171417
TI  - The TolA protein interacts with colicin E1 differently than with other group A
      colicins.
AB  - The 421-residue protein TolA is required for the translocation of group A
      colicins (colicins E1, E2, E3, A, K, and N) across the cell envelope of
      Escherichia coli. Mutations in TolA can render cells tolerant to these colicins
      and cause hypersensitivity to detergents and certain antibiotics, as well as a
      tendency to leak periplasmic proteins. TolA contains a long alpha-helical domain
      which connects a membrane anchor to the C-terminal domain, which is required for
      colicin sensitivity. The functional role of the alpha-helical domain was tested
      by deletion of residues 56 to 169 (TolA delta1), 166 to 287 (TolA delta2), or 54
      to 287 (TolA delta3) of the alpha-helical domain of TolA, which removed the N
      terminal half, the C-terminal half, or nearly the entire alpha-helical domain of
      TolA, respectively. TolA and TolA deletion mutants were expressed from a plasmid
      in an E. coli strain producing no chromosomally encoded TolA. Cellular
      sensitivity to the detergent deoxycholate was increased for each deletion mutant,
      implying that more than half of the TolA alpha-helical domain is necessary for
      cell envelope stability. Removal of either the N- or C-terminal half of the alpha
      helical domain resulted in a slight (ca. 5-fold) decrease in cytotoxicity of the
      TolA-dependent colicins A, E1, E3, and N compared to cells producing wild-type
      TolA when these mutants were expressed alone or with TolQ, -R, and -B. In cells
      containing TolA delta3, the cytotoxicity of colicins A and E3 was decreased by a
      factor of >3,000, and K+ efflux induced by colicins A and N was not detectable.
      In contrast, for colicin E1 action on TolA delta3 cells, there was little
      decrease in the cytotoxic activity (<5-fold) or the rate of K+ efflux, which was
      similar to that from wild-type cells. It was concluded that the mechanism(s) by
      which cellular uptake of colicin E1 is mediated by the TolA protein differs from
      that for colicins A, E3, and N. Possible explanations for the distinct
      interaction and unique translocation mechanism of colicin E1 are discussed.

PMID- 9171418
TI  - Characterization of a thermosensitive Escherichia coli aspartyl-tRNA synthetase
      mutant.
AB  - The Escherichia coli tls-1 strain carrying a mutated aspS gene (coding for
      aspartyl-tRNA synthetase), which causes a temperature-sensitive growth phenotype,
      was cloned by PCR, sequenced, and shown to contain a single mutation resulting in
      substitution by serine of the highly conserved proline 555, which is located in
      motif 3. When an aspS fragment spanning the codon for proline 555 was transformed
      into the tls-1 strain, it was shown to restore the wild-type phenotype via
      homologous recombination with the chromosomal tls-1 allele. The mutated AspRS
      purified from an overproducing strain displayed marked temperature sensitivity,
      with half-life values of 22 and 68 min (at 42 degrees C), respectively, for tRNA
      aminoacylation and ATP/PPi exchange activities. Km values for aspartic acid, ATP,
      and tRNA(Asp) did not significantly differ from those of the native enzyme; thus,
      mutation Pro555Ser lowers the stability of the functional configuration of both
      the acylation and the amino acid activation sites but has no significant effect
      on substrate binding. This decrease in stability appears to be related to a
      conformational change, as shown by gel filtration analysis. Structural data
      strongly suggest that the Pro555Ser mutation lowers the stability of the Lys556
      and Thr557 positions, since these two residues, as shown by the crystallographic
      structure of the enzyme, are involved in the active site and in contacts with the
      tRNA acceptor arm, respectively.

PMID- 9171420
TI  - Transcriptional regulation of delta-aminolevulinic acid dehydratase synthesis by
      oxygen in Bradyrhizobium japonicum and evidence for developmental control of the
      hemB gene.
AB  - An increased demand for cytochromes is associated with symbiotic development and
      microaerobic metabolism in the bacterium Bradyrhizobium japonicum, and evidence
      suggests that hemB, rather than hemA, is the first essential bacterial heme
      synthesis gene in symbiosis with soybean. Steady-state levels of mRNA and protein
      encoded by hemB were strongly and rapidly induced by O2 deprivation as determined
      by RNase protection and immunoblot analyses, but hemH message was not induced.
      Oxygen limitation resulted in a greater-than-10-fold increase in the rate of hemB
      mRNA synthesis as determined by transcriptional runoff experiments, whereas hemH
      transcription was unaffected by the O2 status. Thus, hemB is a regulated gene in
      B. japonicum and is transcriptionally controlled by O2. Unlike the expression in
      parent strain I110, hemB expression was not affected by O2 in the fixJ strain
      7360, and O2-limited cultures of the mutant contained quantities of hemB mRNA and
      protein that were comparable to uninduced levels found in aerobic cells. In
      addition, spectroscopic analysis of cell extracts showed that increases in b- and
      c-type cytochromes and the disappearance of cytochrome aa3 in response to
      microaerobic growth in wild-type cells were not observed in the fixJ mutant. FixJ
      is a key transcriptional regulator that mediates O2-dependent differentiation in
      rhizobia, and therefore hemB expression is under developmental control.
      Furthermore, the data suggest a global control of cytochrome expression and heme
      biosynthesis in response to the cellular O2 status.

PMID- 9171419
TI  - Domains of Escherichia coli acyl carrier protein important for membrane-derived
      oligosaccharide biosynthesis.
AB  - Acyl carrier protein participates in a number of biosynthetic pathways in
      Escherichia coli: fatty acid biosynthesis, phospholipid biosynthesis,
      lipopolysaccharide biosynthesis, activation of prohemolysin, and membrane-derived
      oligosaccharide biosynthesis. The first four pathways require the protein's
      prosthetic group, phosphopantetheine, to assemble an acyl chain or to transfer an
      acyl group from the thioester linkage to a specific substrate. By contrast, the
      phosphopantetheine prosthetic group is not required for membrane-derived
      oligosaccharide biosynthesis, and the function of acyl carrier protein in this
      biosynthetic scheme is currently unknown. We have combined biochemical and
      molecular biological approaches to investigate domains of acyl carrier protein
      that are important for membrane-derived oligosaccharide biosynthesis. Proteolytic
      removal of the first 6 amino acids from acyl carrier protein or chemical
      synthesis of a partial peptide encompassing residues 26 to 50 resulted in losses
      of secondary and tertiary structure and consequent loss of activity in the
      membrane glucosyltransferase reaction of membrane-derived oligosaccharide
      biosynthesis. These peptide fragments, however, inhibited the action of intact
      acyl carrier protein in the enzymatic reaction. This suggests a role for the loop
      regions of the E. coli acyl carrier protein and the need for at least two regions
      of the protein for participation in the glucosyltransferase reaction. We have
      purified acyl carrier protein from eight species of Proteobacteria (including
      representatives from all four subgroups) and characterized the proteins as active
      or inhibitory in the membrane glucosyltransferase reaction. The complete or
      partial amino acid sequences of these acyl carrier proteins were determined. The
      results of site-directed mutagenesis to change amino acids conserved in active,
      and altered in inactive, acyl carrier proteins suggest the importance of residues
      Glu-4, Gln-14, Glu-21, and Asp-51. The first 3 of these residues define a face of
      acyl carrier protein that includes the beginning of the loop region, residues 16
      to 36. Additionally, screening for membrane glucosyltransferase activity in
      membranes from bacterial species that had acyl carrier proteins that were active
      with E. coli membranes revealed the presence of glucosyltransferase activity only
      in the species most closely related to E. coli. Thus, it seems likely that only
      bacteria from the Proteobacteria subgroup gamma-3 have periplasmic glucans
      synthesized by the mechanism found in E. coli.

PMID- 9171421
TI  - Posttranslational control of the algT (algU)-encoded sigma22 for expression of
      the alginate regulon in Pseudomonas aeruginosa and localization of its antagonist
      proteins MucA and MucB (AlgN).
AB  - Pseudomonas aeruginosa strains associated with cystic fibrosis are often mucoid
      due to the copious production of alginate, an exopolysaccharide and virulence
      factor. Alginate gene expression is transcriptionally controlled by a gene
      cluster at 68 min on the chromosome: algT (algU)-mucA-mucB (algN)-mucC (algM)
      mucD (algY). The algT gene encodes a 22-kDa alternative sigma factor (sigma22)
      that autoregulates its own promoter (PalgT) as well as the promoters of algR,
      algB, and algD. The other genes in the algT cluster appear to regulate the
      expression or activity of sigma22. The goal of this study was to better
      understand the functional interactions between sigma22 and its antagonist
      regulators during alginate production. Nonmucoid strain PAO1 was made to
      overproduce alginate (indicating high algD promoter activity) through increasing
      sigma22 in the cell by introducing a plasmid clone containing algT from
      mucA22(Def) strain FRD1. However, the bacterial cells remained nonmucoid if the
      transcriptionally coupled mucB on the clone remained intact. This suggested that
      a stoichiometric relationship between sigma22 and MucB may be required to control
      sigma factor activity. When the transcription and translational initiation of
      algT were measured with lacZ fusions, alginate production correlated with only
      about a 1.2- to 1.7-fold increase in algT-lacZ activity, respectively. An algR
      lacZ transcriptional fusion showed a 2.8-fold increase in transcription with
      alginate production under the same conditions. A Western blot analysis of total
      cell extracts showed that sigma22 was approximately 10-fold higher in strains
      that overproduced alginate, even though algT expression increased less than 2
      fold. This suggested that a post-transcriptional mechanism may exist to
      destabilize sigma22 in order to control certain sigma22-dependent promoters like
      algD. By Western blotting and phoA fusion analyses, the MucB antagonist of
      sigma22 was found to localize to the periplasm of the cell. Similar experiments
      suggest that MucA localizes to the inner membrane via one transmembrane domain
      with amino- and carboxy-terminal domains in the cytoplasm and periplasm,
      respectively. These data were used to propose a model in which MucB-MucA-sigma22
      interact via an inner membrane complex that controls the stability of sigma22
      protein in order to control alginate biosynthesis.

PMID- 9171422
TI  - Insertion mutagenesis of the lac repressor and its implications for structure
      function analysis.
AB  - We recently developed a simple technique for the generation of relatively large
      (31-codon) insertion mutations in cloned genes. To test whether the analysis of
      such mutations could provide insight into structure-function relationships in
      proteins, we examined a set of insertion mutants of the Escherichia coli lac
      repressor (LacI). Representatives of several LacI mutant classes were recovered,
      including mutants which exhibit fully active, inducer-insensitive, or weak
      dominant-negative phenotypes. The various properties of the recovered mutants
      agree with previous biophysical, biochemical, and genetic data for the protein.
      In particular, the results support the prior designation of mutationally tolerant
      spacer regions of LacI as well as proposed differences in dimerization
      interactions among regions of the protein core domain. These findings suggest
      that the analysis of 31-codon insertion mutations may provide a simple approach
      for characterizing structure-function relationships in proteins for which high
      resolution structures are not available.

PMID- 9171423
TI  - Function of conserved histidine-243 in phosphatase activity of EnvZ, the sensor
      for porin osmoregulation in Escherichia coli.
AB  - EnvZ and OmpR are the sensor and response regulator proteins of a two-component
      system that controls the porin regulon of Escherichia coli in response to
      osmolarity. Three enzymatic activities are associated with EnvZ: autokinase, OmpR
      kinase, and OmpR-phosphate (OmpR-P) phosphatase. Conserved histidine-243 is
      critical for both autokinase and OmpR kinase activities. To investigate its
      involvement in OmpR-P phosphatase activity, histidine-243 was mutated to several
      other amino acids and the phosphatase activity of mutated EnvZ was measured both
      in vivo and in vitro. In agreement with previous reports, we found that certain
      substitutions abolished the phosphatase activity of EnvZ. However, a significant
      level of phosphatase activity remained when histidine-243 was replaced with
      certain amino acids, such as tyrosine. In addition, the phosphatase activity of a
      previously identified kinase- phosphatase+ mutant was not abolished by the
      replacement of histidine-243 with asparagine. These data indicated that although
      conserved histidine-243 is important for the phosphatase activity, a histidine
      243-P intermediate is not required. Our data are consistent with a previous model
      that proposes a common transition state with histidine-243 (EnvZ) in close
      contact with aspartate-55 (OmpR) for both OmpR phosphorylation and
      dephosphorylation. Phosphotransfer occurs from histidine-243-P to aspartate-55
      during phosphorylation, but water replaces the phosphorylated histidine side
      chain leading to hydrolysis during dephosphorylation.

PMID- 9171424
TI  - Evidence for the bacterial origin of genes encoding fermentation enzymes of the
      amitochondriate protozoan parasite Entamoeba histolytica.
AB  - Entamoeba histolytica is an amitochondriate protozoan parasite with numerous
      bacterium-like fermentation enzymes including the pyruvate:ferredoxin
      oxidoreductase (POR), ferredoxin (FD), and alcohol dehydrogenase E (ADHE). The
      goal of this study was to determine whether the genes encoding these cytosolic E.
      histolytica fermentation enzymes might derive from a bacterium by horizontal
      transfer, as has previously been suggested for E. histolytica genes encoding heat
      shock protein 60, nicotinamide nucleotide transhydrogenase, and superoxide
      dismutase. In this study, the E. histolytica por gene and the adhE gene of a
      second amitochondriate protozoan parasite, Giardia lamblia, were sequenced, and
      their phylogenetic positions were estimated in relation to POR, ADHE, and FD
      cloned from eukaryotic and eubacterial organisms. The E. histolytica por gene
      encodes a 1,620-amino-acid peptide that contained conserved iron-sulfur- and
      thiamine pyrophosphate-binding sites. The predicted E. histolytica POR showed
      fewer positional identities to the POR of G. lamblia (34%) than to the POR of the
      enterobacterium Klebsiella pneumoniae (49%), the cyanobacterium Anabaena sp.
      (44%), and the protozoan Trichomonas vaginalis (46%), which targets its POR to
      anaerobic organelles called hydrogenosomes. Maximum-likelihood, neighbor-joining,
      and parsimony analyses also suggested as less likely E. histolytica POR sharing
      more recent common ancestry with G. lamblia POR than with POR of bacteria and the
      T. vaginalis hydrogenosome. The G. lamblia adhE encodes an 888-amino-acid fusion
      peptide with an aldehyde dehydrogenase at its amino half and an iron-dependent
      (class 3) ADH at its carboxy half. The predicted G. lamblia ADHE showed extensive
      positional identities to ADHE of Escherichia coli (49%), Clostridium
      acetobutylicum (44%), and E. histolytica (43%) and lesser identities to the class
      3 ADH of eubacteria and yeast (19 to 36%). Phylogenetic analyses inferred a
      closer relationship of the E. histolytica ADHE to bacterial ADHE than to the G.
      lamblia ADHE. The 6-kDa FD of E. histolytica and G. lamblia were most similar to
      those of the archaebacterium Methanosarcina barkeri and the delta-purple
      bacterium Desulfovibrio desulfuricans, respectively, while the 12-kDa FD of the
      T. vaginalis hydrogenosome was most similar to the 12-kDa FD of gamma-purple
      bacterium Pseudomonas putida. E. histolytica genes (and probably G. lamblia
      genes) encoding fermentation enzymes therefore likely derive from bacteria by
      horizontal transfer, although it is not clear from which bacteria these amebic
      genes derive. These are the first nonorganellar fermentation enzymes of
      eukaryotes implicated to have derived from bacteria.

PMID- 9171425
TI  - Composition and primary structure of the F1F0 ATP synthase from the obligately
      anaerobic bacterium Clostridium thermoaceticum.
AB  - The subunit composition and primary structure of the proton-translocating F1F0
      ATP synthase have been determined in Clostridium thermoaceticum. The isolated
      enzyme has a subunit composition identical to that of the F1F0 ATP synthase
      purified from Clostridium thermoautotrophicum (A. Das, D. M. Ivey, and L. G.
      Ljungdahl, J. Bacteriol. 179:1714-1720, 1997), both having six different
      polypeptides. The molecular masses of the six subunits were 60, 50, 32, 17, 19,
      and 8 kDa, and they were identified as alpha, beta, gamma, delta, epsilon, and c,
      respectively, based on their reactivity with antibodies against the F1 ATPase
      purified from C. thermoautotrophicum and by comparing their N-terminal amino acid
      sequences with that deduced from the cloned genes of the C. thermoaceticum atp
      operon. The subunits a and b found in many bacterial ATP synthases could not be
      detected either in the purified ATP synthase or crude membranes of C.
      thermoaceticum. The C. thermoaceticum atp operon contained nine genes arranged in
      the order atpI (i), atpB (a), atpE (c), atpF (b), atpH (delta), atpA (alpha),
      atpG (gamma), atpD (beta), and atpC (epsilon). The deduced protein sequences of
      the C. thermoaceticum ATP synthase subunits were comparable with those of the
      corresponding subunits from Escherichia coli, thermophilic Bacillus strain PS3,
      Rhodospirillum rubrum, spinach chloroplasts, and the cyanobacterium Synechococcus
      strain PCC 6716. The analysis of total RNA by Northern hybridization experiments
      reveals the presence of transcripts (mRNA) of the genes i, a, and b subunits not
      found in the isolated enzyme. Analysis of the nucleotide sequence of the atp
      genes reveals overlap of the structural genes for the i and a subunits and the
      presence of secondary structures (in the b gene) which could influence the
      posttranscriptional regulation of the corresponding genes.

PMID- 9171426
TI  - Structural characterization of the lipids A of three Bordetella bronchiseptica
      strains: variability of fatty acid substitution.
AB  - The structures of lipids A isolated from the lipopolysaccharides (LPSs;
      endotoxins) of three different pathogenic Bordetella bronchiseptica strains were
      investigated by chemical composition and methylation analysis, gas chromatography
      mass spectrometry, nuclear magnetic resonance, and plasma desorption mass
      spectrometry (PDMS). The analyses revealed that the LPSs contain the classical
      lipid A bisphosphorylated beta-(1-->6)-linked D-glucosamine disaccharide with
      hydroxytetradecanoic acid in amide linkages. Their structures differ from that of
      the lipid A of Bordetella pertussis endotoxin by the replacement of
      hydroxydecanoic acid on the C-3 position with hydroxydodecanoic acid or
      dodecanoic acid and the presence of variable amounts of hexadecanoic acid. The
      dodecanoic acid is the first nonhydroxylated fatty acid to be found directly
      linked to a lipid A glucosamine. The lipids A were heterogeneous and composed of
      one to three major and several minor molecular species. The fatty acids in ester
      linkage were localized by PDMS of chemically modified lipids A. B. pertussis
      lipids A are usually hypoacylated with respect to those of enterobacterial lipids
      A. However, one of the three B. bronchiseptica strains had a major hexaacylated
      molecular species. C-4 and C-6' hydroxyl groups of the backbone disaccharide were
      unsubstituted, the latter being the proposed attachment site of the
      polysaccharide. The structural variability seen in these three lipids A was
      unusual for a single species and may have consequences for the pathogenicity of
      this Bordetella species.

PMID- 9171427
TI  - Role of GATA factor Nil2p in nitrogen regulation of gene expression in
      Saccharomyces cerevisiae.
AB  - We have identified the product of the NIL2 gene of Saccharomyces cerevisiae which
      contains a zinc finger region highly homologous to those of the GATA factors
      Gln3p and Nil1p as an antagonist of Nil1p and to a lesser extent of Gln3p. The
      expression of many nitrogen-regulated genes of Saccharomyces cerevisiae requires
      activation by GATA factor Gln3p or Nil1p and is prevented by the presence of
      glutamine in the growth medium. Disruption of NIL2 results in a great increase in
      the expression of NIL1 and of GAP1, the structural gene for the general amino
      acid permease, in glutamine-grown cells in response to activation by Nil1p. The
      primary effect of the elimination of Nil2p appears to be an increase in the
      intracellular level of Nil1p, which in turn is responsible for increased
      expression of GAP1. Experiments using an artificial UAS (upstream activating
      site) consisting of three GATAAGATAAG sites revealed that Nil2p exerts its effect
      by competing primarily with Nil1p and less effectively with Gln3p for these
      sites. Apparently, the principal role of Nil2p is to prevent activation of
      transcription by Nil1p unless Nil1p has been converted to a more active state by
      the absence of glutamine and glutamate.

PMID- 9171428
TI  - The Staphylococcus aureus ileS gene, encoding isoleucyl-tRNA synthetase, is a
      member of the T-box family.
AB  - The Staphylococcus aureus ileS gene, encoding isoleucyl-tRNA synthetase (IleRS),
      contains a long mRNA leader region. This region exhibits many of the features of
      the gram-positive synthetase gene family, including the T box and leader region
      terminator and antiterminator. The terminator was shown to be functional in vivo,
      and readthrough increased during growth in the presence of mupirocin, an
      inhibitor of IleRS activity. The S. aureus ileS leader structure includes several
      critical differences from the other members of the T-box family, suggesting that
      regulation of this gene in S. aureus may exhibit unique features.

PMID- 9171429
TI  - Escherichia coli endonuclease VIII: cloning, sequencing, and overexpression of
      the nei structural gene and characterization of nei and nei nth mutants.
AB  - Escherichia coli possesses two DNA glycosylase/apurinic lyase activities with
      overlapping substrate specificities, endonuclease III and endonuclease VIII, that
      recognize and remove oxidized pyrimidines from DNA. Endonuclease III is encoded
      by the nth gene. Endonuclease VIII has now been purified to apparent homogeneity,
      and the gene, nei, has been cloned by using reverse genetics. The gene nei is
      located at 16 min on the E. coli chromosome and encodes a 263-amino-acid protein
      which shows significant homology in the N-terminal and C-terminal regions to five
      bacterial Fpg proteins. A nei partial deletion replacement mutant was
      constructed, and deletion of nei was confirmed by genomic PCR, activity analysis,
      and Western blot analysis. nth nei double mutants were hypersensitive to ionizing
      radiation and hydrogen peroxide but not as sensitive as mutants devoid of base
      excision repair (xth nfo). Single nth mutants exhibited wild-type sensitivity to
      X rays, while nei mutants were consistently slightly more sensitive than the wild
      type. Double mutants lacking both endonucleases III and VIII exhibited a strong
      spontaneous mutator phenotype (about 20-fold) as determined by a rifampin forward
      mutation assay. In contrast to nth mutants, which showed a weak mutator
      phenotype, nei single mutants behaved as the wild type.

PMID- 9171430
TI  - Characterization of endonuclease III (nth) and endonuclease VIII (nei) mutants of
      Escherichia coli K-12.
AB  - The nth and nei genes of Escherichia coli affect the production of endonuclease
      III and endonuclease VIII, respectively, glycosylases/apurinic lyases that attack
      DNA damaged by oxidizing agents. Here, we provide evidence that oxidative lethal
      lesions are repaired by both endonuclease III and endonuclease VIII and that
      spontaneous mutagenic lesions are repaired mainly by endonuclease III.

PMID- 9171431
TI  - Membrane topology of the metal-tetracycline/H+ antiporter TetA(K) from
      Staphylococcus aureus.
AB  - A series of fusions to the reporter proteins alkaline phosphatase and beta
      galactosidase have been constructed in the predicted periplasmic and cytoplasmic
      loops of TetA(K), a protein responsible for efflux-mediated tetracycline
      resistance in Staphylococcus aureus. The results support a topological model of
      14 transmembrane segments for TetA(K).

PMID- 9171432
TI  - Characterization of DNA binding sites for the BvgA protein of Bordetella
      pertussis.
AB  - Expression of virulence-associated genes in Bordetella pertussis is under the
      control of the pleiotropic regulator BvgA. Although previous studies have
      identified recognition sequences for BvgA in several promoter regions, their
      structures have not been clearly characterized. We show that the BvgA binding
      sites within the bvgp(1) and cyaA promoters consist of inverted repeats and
      suggest that inverted-repeat motifs may represent the recognition elements for
      DNA-BvgA interaction.

PMID- 9171433
TI  - Maximum activity of recombinant ribulose 1,5-bisphosphate carboxylase/oxygenase
      of Anabaena sp. strain CA requires the product of the rbcX gene.
AB  - Filamentous cyanobacteria of the genus Anabaena contain a unique open reading
      frame, rbcX, which is juxtaposed and cotranscribed with the genes (rbcL and rbcS)
      encoding form I ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO).
      Plasmid constructions containing the genes from Anabaena sp. strain CA were
      prepared, and expression studies in Escherichia coli indicated that the product
      of the rbcX gene mimicked the ability of chaperonin proteins to facilitate the
      proper folding of recombinant RubisCO proteins. The purified recombinant Anabaena
      sp. strain CA RubisCO, much like the RubisCO enzymes from other cyanobacteria,
      was shown not to undergo inhibition of activity during a time course experiment,
      and the properties of this chaperoned recombinant protein appear to be consistent
      with those of the enzyme isolated from the native organism.

PMID- 9171434
TI  - Integration host factor is required for 1,2-propanediol-dependent transcription
      of the cob/pdu regulon in Salmonella typhimurium LT2.
AB  - We show that integration host factor (IHF) is required for the activation of
      transcription of the cobalamin biosynthetic (cob) and 1,2-propanediol (1,2-PDL)
      utilization (pdu) operons in Salmonella typhimurium LT2. A lack of IHF affected
      transcription of the cob/pdu regulon in at least two ways. First, the level of
      the regulatory protein PocR was decreased in ihfB (formerly himD) mutants, as
      judged by Western blot analysis with polyclonal antiserum raised against PocR.
      Second, even when PocR was available, in the absence of IHF, PocR was unable to
      activate transcription of cob/pdu in response to 1,2-PDL. This result suggested
      an additional role for IHF in PocR-dependent transcription activation. Consistent
      with these findings, ihfB mutants of this bacterium were unable to use 1,2-PDL as
      a carbon or energy source.

PMID- 9171435
TI  - Cloning, characterization, and sequence analysis of the clcE gene encoding the
      maleylacetate reductase of Pseudomonas sp. strain B13.
AB  - A 3,167-bp PstI fragment of genomic DNA from Pseudomonas sp. strain B13 was
      cloned and sequenced. The gene clcE consists of 1,059 nucleotides encoding a
      protein of 352 amino acids with a calculated mass of 37,769 Da which showed
      maleylacetate reductase activity. The protein had significant sequence
      similarities with the polypeptides encoded by tcbF of pP51 (59.4% identical
      positions), tfdF of pJP4 (55.1%), and tftE of Burkholderia cepacia AC1100
      (53.1%). The function of TcbF as maleylacetate reductase was established by an
      enzyme assay.

PMID- 9171436
TI  - The alanine racemase gene is essential for growth of Lactobacillus plantarum.
AB  - The Lactobacillus plantarum alr gene encoding alanine racemase was cloned by
      complementation of an Escherichia coli Alr- DadX- double mutant strain. Knockout
      of the alr gene abolished all measurable alanine racemase activity, and the
      mutant was shown to be strictly dependent on D-alanine for growth.

PMID- 9171437
TI  - Identification of a second endogenous Porphyromonas gingivalis insertion element.
AB  - In this study a second endogenous Porphyromonas gingivalis insertion element (IS
      element) that is capable of transposition within P. gingivalis was identified.
      Nucleotide sequence analysis of the Tn4351 insertion site in a P. gingivalis
      Tn4351-generated transconjugant showed that a complete copy of the previously
      unidentified IS element, designated PGIS2, had inserted into IS4351R in Tn4351.
      PGIS2 is 1,207 bp in length with 19-bp imperfect terminal inverted repeats, and
      insertion resulted in a duplicated 10-bp target sequence. Results of Southern
      hybridization of chromosomal DNA isolated from several P. gingivalis strains with
      a PGIS2-specific probe demonstrated that the number of copies of PGIS2 per genome
      varies among different P. gingivalis strains. Computer analysis of the putative
      polypeptide encoded by PGIS2 revealed strong homologies to the products encoded
      by IS1358 from Vibrio cholerae, ISAS1 from Aeromonas salmonicida, and H-rpt in
      Escherichia coli K-12.

PMID- 9171438
TI  - Formation of pH and potential gradients by the reconstituted Azotobacter
      vinelandii cytochrome bd respiratory protection oxidase.
AB  - To directly characterize the bioenergetic properties of the cytochrome bd
      terminating branch of the Azotobacter vinelandii electron transport chain, the
      purified cytochrome bd oxidase was reconstituted into a phospholipid environment
      consisting of phosphatidylethanolamine and phosphatidylglycerol (3:1). The
      average diameter of the proteoliposomes after extrusion through a polycarbonate
      membrane was 94 +/- 4 nm. Initiation of respiration upon the addition of 20
      microM ubiquinone-1 to proteoliposomes loaded with the pH-sensitive dye pyranine
      resulted in an immediate alkalization of the vesicle lumen by an average pH
      change of 0.11 unit. This pH gradient was readily collapsed upon the addition of
      nigericin, carbonyl cyanide p-(tri-fluoromethoxy) phenyl-hydrazone, gramicidin,
      Triton X-100, or 2-heptyl-4-hydroxyquinoline N-oxide (HQNO). Proteoliposomal
      respiration initiated in the presence of the potentiometric membrane dye
      rhodamine 123 caused the generation of a transmembrane potential; the potential
      was collapsed upon the addition of either valinomycin or HQNO. The formation of
      both pH and potential gradients during turnover demonstrates that the A.
      vinelandii cytochrome bd oxidase is coupled to energy conservation in vivo.

PMID- 9171439
TI  - The Escherichia coli flagellar transcriptional activator flhD regulates cell
      division through induction of the acid response gene cadA.
AB  - FlhD is a positive regulator of cadA. A mutant with a transposon-mediated lacZ
      fusion to cadA exhibited a cell division phenotype similar to that of the flhD
      mutant and had FlhD-dependent beta-galactosidase activity. Under different growth
      conditions, the cell division rate correlated with the level of expression of
      cadA.

PMID- 9171440
TI  - Neurogenesis in Drosophila: an historical perspective and some prospects.

PMID- 9171441
TI  - On the function of proneural genes in Drosophila.
AB  - The proneural genes in Drosophila render ectodermal cells competent to adopt a
      neural fate. Moreover, they also initiate the program of mutual inhibition, which
      will ultimately lead to their own inactivation. Recent advances that elucidate
      the regulatory relationships between proneural and neurogenic genes are
      discussed.

PMID- 9171442
TI  - Patterning of the adult peripheral nervous system of Drosophila.
AB  - The peripheral nervous system (PNS) of the adult Drosophila melanogaster
      comprises over one thousand sensory organs (bristles and other types of sensilla)
      displayed in stereotyped positions of the epidermis. This two-dimensional pattern
      of sensory organs is generated by the emergence of the sensillum mother cells at
      specific positions of the imaginal discs, the precursors of the adult epidermis.
      These positions are largely specified by the interplay of three sets of genes:
      the proneural genes, their antagonists, and the neurogenic genes. The proneural
      genes confer upon cells the ability to become neural precursors. Among them,
      achaete and scute, two genes that encode transcriptional activators of the basic
      region-helix-loop-helix (bHLH) family, are most important for generating the
      adult PNS. Their expression is restricted to groups of cells, the proneural
      clusters, which appear at specific positions of the imaginal discs. Sensory organ
      precursor cells are born within these clusters. The known proneural antagonists
      either titrate these proteins by forming inactive complexes (extramacrochaetae)
      or repress achaete/scute expression at specific sites (i.e., hairy). In both
      cases, they refine sensory organ positioning by reducing the number of cells
      competent to become sensory organs. The neurogenic genes mediate cell-cell
      interactions that prevent most competent cells of a proneural cluster from
      becoming sensory organ mother cells. Depending on the size and shape of the
      proneural clusters and on their overlaps with regions of maxima or minima of
      expression of antagonists, sensory organs are generated either as single elements
      at unique positions, or as linear arrays containing many elements, or as
      characteristically shaped, two-dimensional arrangements covering specific regions
      of the fly's body.

PMID- 9171443
TI  - Notch signaling in development.

PMID- 9171444
TI  - Role of suppressor of hairless in the delta-activated Notch signaling pathway.
AB  - The Notch protein (N) acts as a transmembrane receptor for intercellular signals
      controlling cell fate choices in vertebrates and invertebrates. Genetical and
      molecular evidence indicates that, during Drosophila neurogenesis, an
      evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)],
      transduces the signal of N activation by its ligand Delta (D1). Su(H) plays a
      direct role in the immediate response of the genome to N signaling by up
      regulating the transcription of the Enhancer of split Complex [E(spl)-C] genes.
      These findings suggest that the N transduction pathway can be described as a
      simple, linear cascade of molecular activation. At the molecular level, the
      mechanism of Su(H) "activation" is yet unknown. Two non-exclusive models have
      been proposed. In the first one, Su(H) binds to inactive N at the membrane. The
      binding of D1 to N in the extracellular space somehow interferes with the N
      mediated cytoplasmic retention of Su(H), resulting in the nuclear translocation
      and "activation" of Su(H). In the second model, DNA-bound Su(H) is proposed to be
      "activated" in the nucleus by the direct binding of a processed form of N, acting
      as a transcriptional coactivator. This nuclear N protein would be generated by
      the ligand-induced proteolytic cleavage of the N transmembrane receptor.

PMID- 9171446
TI  - Comparative aspects of Notch signaling in lower and higher eukaryotes.
AB  - The Drosophila melanogaster Notch gene encodes a receptor that is part of a cell
      cell signaling mechanism that is used throughout the development of the fly to
      regulate a wide variety of cell fate decisions, including some neuronal
      decisions. The Caenorhabditis elegans Notch-like genes lin-12 and glp-1 play
      roles that are similar to that of Notch, and studies of this signaling pathway in
      both organisms have led to models of how the pathway might function. Recent
      developments in the study of Notch signaling include the isolation of Notch
      homologs from a variety of vertebrate species. Here we compare what has been
      learned from studies of Notch-related genes in vertebrates to what is known about
      Notch signaling in invertebrates, and we discuss the implications of these data
      for existing models of Notch pathway signaling.

PMID- 9171445
TI  - Expression and function of Enhancer of split bHLH proteins during Drosophila
      neurogenesis.
AB  - The products of the Enhancer of split complex are required during neurogenesis
      for neural fate to be limited to a subset of cells within the ectoderm. Deletions
      which remove the complex lead to neural hypertrophy. The complex encodes seven
      related basic-helix-loop-helix transcription factors which are expressed in
      response to Notch activation. They accumulate in the cells surrounding the
      delaminating neuroblast where they prevent cells from adopting the neural fate,
      most likely by antagonising either directly or indirectly the actions of the
      proneural genes encoded by the achaete-scute complex. The individual roles of the
      seven different Enhancer of split proteins remains unclear, since their functions
      are at least partially redundant. However, the Enhancer of split complex is
      required in many other processes where Notch is active; the function of the
      individual proteins may relate to their roles in other developmental decisions or
      to their expression in distinct regions.

PMID- 9171447
TI  - Diverse roles for the Notch receptor in the development of D. melanogaster.
AB  - Notch proteins appear to be involved in cell fate commitments with deep
      evolutionary roots. Homologues have been shown to play key roles in the
      development of nematodes, insects, amphibia, and mammals. Activity of the Notch
      receptor has been observed in the patterning of ectoderm, mesoderm, and endoderm,
      indicating an origin prior to the functional differentiation of these germ
      layers. To understand how a single receptor can participate so widely in
      development, we have been examining the role of specific extracellular segments
      of Notch. Early studies of mutations affecting widely separated EGF-like elements
      of Notch first raised the possibility for interaction with multiple ligands.
      Biochemical approaches, and exhaustive structure function studies in transgenic
      Drosophila are beginning to reveal how this receptor is activated, and point to a
      range of physical interactions with other proteins.

PMID- 9171448
TI  - CNS midline development in Drosophila.
AB  - The first cells specified during CNS development of vertebrates and invertebrates
      are the cells located at the midline of the neuroepithelium. In Drosophila the
      development of these cells requires inductive signals from the mesoderm. Later in
      CNS development, the midline cells are in turn influencing the flanking
      neuroectoderm, contributing to the establishment of dorsoventral positional
      information. During axonal pattern formation the midline cells are required in
      guiding commissural growth cones towards and across the midline. The midline
      consists of only few, easily identifiable neuronal and glial cells per segment.
      The development of midline glial cells is relatively well understood. Their
      differentiation appears to be controlled by the concomitant expression of two
      different sets of transcription factors. Activation of glial differentiation
      mediated by the ETS transcription factor encoded by pointed (whose activity
      depends on EGF-receptor signalling) occurs in concert with repression of neuronal
      differentiation mediated by the Zn-finger transcription factor encoded by
      tramtrack.

PMID- 9171449
TI  - Identification of okra mosaic virus from Indigofera spicata in Nigeria.
AB  - Okra mosaic virus (OMV, tymovirus group) was isolated from Indigofera spicata
      plants growing at the International Institute of Tropical Agriculture (IITA) in
      Ibadan, Nigeria. Its identity was established on the basis of particle
      morphology, analysis of viral coat protein and nucleic acid and serology. In
      reciprocal agar gel diffusion tests, the virus isolate from I. spicata and an OMV
      isolate from okra in Ibadan (OMV-Ibadan isolate) were found to be serologically
      identical. However, because the isolates differ in symptom induction in various
      host plants, the name OMV-Indigofera isolate is suggested. This is the first
      report on the occurence of OMV in I. spicata.

PMID- 9171450
TI  - Cytotoxic T lymphocyte control during ectromelia (mousepox) virus infection:
      interaction between MHC-restricted cells analyzed by non-radioactive fluorometry.
AB  - Cytotoxic T lymphocyte (CTL) activity of draining lymph node (DLN) cells isolated
      from BALB/c mice infected with ectromelia virus (EV) was examined using a
      fluorometric cell-mediated cytotoxicity (CMC) assay. Specific lysis of target
      cells A20 and EMT-6 primed with EV was demonstrated. The classical CD8+ cytolytic
      pathway dominated (72.7%) as compared to that of CD4+ (27.3%) in the cellular
      response during acute EV infection. Also an alternative method for determining
      CMC, employing a bisbenzamide dye for labelling target cells, is described.
      Coefficient variations of relative fluorescence were below 6%, that makes the
      method sensitive and reliable.

PMID- 9171451
TI  - Immunogenicity of immunostimulating complexes of Japanese encephalitis virus in
      experimental animals.
AB  - Immunogenicity of immunostimulating complexes (ISCOMs) of Japanese encephalitis
      virus (JEV) were studied in mice, rabbits and monkeys. Two doses of JE ISCOMs
      elicited a strong immune response in mice with an uniform distribution in IgG
      subclasses. Different time intervals between the two doses of ISCOMs led to
      similar titers of antibodies. Rabbits and monkeys immunized with ISCOMs developed
      strong neutralizing immune, response. Mice immunized with ISCOMs demonstrated
      cell-mediated immunity (CMI) as evidenced by T cell proliferation and macrophage
      migration inhibition (MMI) assays.

PMID- 9171452
TI  - Western blot analysis of the reactivity between envelope proteins of hepatitis B
      viruses from Brazilian carriers and antibodies raised against recombinant
      hepatitis B vaccines.
AB  - A Western blot assay was standardized to evaluate the antigenic reactivity of
      hepatitis B virus (HBV) strains circulating in Brazilian population with
      antibodies raised against recombinant hepatitis B (HB) vaccines. In this assay,
      HBV envelope proteins from infected human blood were detected by antibodies from
      rabbits immunized with either of two recombinant vaccines. These were Engerix B
      (Smith Kline Beecham, Belgium) containing exclusively S protein particles and TGP
      943 (Takeda Chemical Industries, Japan) containing M protein particles. Forty
      seven serum samples, presenting HB surface antigen. (HBsAg) reverse passive
      haemagglutination assay (RPHA) titers ranging from 1:32 to > or =1:4096 after HBV
      particles concentration, were tested. Twenty-seven samples were from acute
      hepatitis cases and 20 were from chronic cases (11 from cirrhotic patients and 9
      from asymptomatic carriers). Four HBV serotypes, adw2, adw4, ayw2 and ayw3, were
      identified in these samples. Infectivity of these sera was evaluated by HBV DNA
      detection by polymerase chain reaction (PCR). HBV DNA was present in 62% of
      samples from acute cases and in all samples from chronic cases. Despite the
      differences between serotypes, genotypes, forms of infection, and infectivity of
      the samples, antibodies against both vaccines reacted with HBV envelope proteins
      from all but one sample. In one sample from cirrhotic patient, only a small
      protein of unexpected size reacted with TGP-943 antibodies.

PMID- 9171453
TI  - Identification and characterization of differentiating soluble antigens of sheep
      and goat poxviruses.
AB  - Soluble antigens of sheep and goat poxviruses (SPV, GPV) were isolated and
      purified from scab suspensions prepared from lesions of experimentally infected
      homologous hosts. The soluble antigens were then subjected to sequential ammonium
      sulphate precipitation. All the obtained fractions reacted in counter
      immunoelectrophoresis (CIE) with both the antisera against SPV and GPV except the
      fraction obtained at 30% saturation level (30% SSPV), which did not react with
      antiserum against GPV. This differentiating soluble SPV antigen was found to
      consist of 210 K proteins in exclusion chromatography. The 210 K proteins
      contained 3 polypeptides of 100, 35 and 17 K in polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). The study
      thus gave an evidence that the SPV-specific proteins are of a higher molecular
      mass nature.

PMID- 9171454
TI  - Protein-tyrosine phosphatase activity of Coxiella burnetii that inhibits human
      neutrophils.
AB  - Supernatants prepared from disrupted Coxiella burnetii possess acid phosphatase
      (ACP) activity that apparently accounts for the inhibition of the metabolic burst
      of formyl-Met-Leu-Phe(fMLP)-stimulated human neutrophils. Results are presented
      regarding purification and biochemical-biological characterization of the ACP.
      The highly purified enzyme, which exhibited an apparent M(r) of 91 K and optimal
      activity at pH 5.0, also inhibited neutrophils. The enzyme retained full activity
      at pH 4.5, 5.5, and 7.4, when incubated overnight at 0 degrees C and room
      temperature; at pH 5.5, it retained full activity after overnight incubation at
      37 degrees C. Apparently, the enzyme contains asparagine-linked but not serine-
      or threonine-linked glycan residues since its treatment with N-glycosidase F
      (PNGase F) decreased its M(r) to 87 K and no changes were detected with O
      glycosidase. The enzyme's capacity to hydrolyze phosphate from a number of
      phosphate-containing compounds was examined; five phosphocompounds were
      significantly hydrolyzed: 5'-CMP > fructose 1,6-diphosphate > tyrosine phosphate
      > 3'-AMP > 5'-AMP. The ACP also dephosphorylated (32)P-Raytide, a phosphotyrosine
      containing peptide. Dephosphorylation of Raytide was inhibited by the following
      phosphatase inhibitors: sodium molybdate, potassium fluoride, sodium ortho
      vanadate and D2, a heteropolymolybdate compound. These results indicate that C.
      burnetii ACP may play a role in disrupting tyrosine
      phosphorylation/dephosphorylation reactions associated with the signal
      transduction pathway culminating in the metabolic burst. Interestingly, Western
      blot analysis of ACP-inhibited neutrophils showed a marked increase in tyrosine
      phosphorylation of a 44 K protein as compared to uninhibited cells.

PMID- 9171455
TI  - Hepatitis B virus core-preS2 particles expressed by recombinant vaccinia virus.
AB  - Vaccinia virus (VV) recombinants expressing hepatitis B virus (HBV) surface
      (HBsAg) or core (HBcAg) antigens (Kunke et al., Virology 195, 132 - 139 (1993)]
      have been shown to raise specific antibodies in mice, nevertheless the levels of
      antibodies reactive with the preS2 and S antigens were low. In an attempt to
      enhance the immunogenicity of HBsAg-preS2, a fused C-preS2 gene was constructed.
      The fusion protein was expressed in E. coli and displayed both HBcAg and preS2
      antigen as demonstrated by enzyme-linked immunosorbent assay (ELISA). The same
      gene was then expressed using recombinant VV and chimerical particles whose size
      and density were similar to those of native HBV core particles produced in CV-1
      cells infected with recombinant VV. Unlike HBcAg, preS2 antigen could not be
      detected on these particles by ELISA but was revealed by immunoblot analysis
      only. The immunogenicity of the recombinant VV was evaluated in mice. Antibodies
      to HBcAg and VV antigen but not to preS2 antigen were found in sera of animals
      inoculated with 10(7) PFU of the recombinant VV. Presumably, HBcAg-preS2
      particles produced in E. coli and in eukaryotic cells have a different
      conformation, and the presence of preS2 antigen on the surface of chimerical
      particle might be necessary for a pronounced antibody response.

PMID- 9171456
TI  - Properties of Syrian hamster cells transformed by human papillomavirus type 16.
AB  - Adult Syrian hamster kidney cells were transfected with a mixture of plasmids
      containing human papillomavirus type 16 (HPV16) E6/E7 open reading frames (ORFs),
      activated Ha-ras gene and neomycin resistance gene. From these cultures two lines
      were isolated which were oncogenic for newborn and 5-day-old but not for 3-week
      old hamsters. Sublines oncogenic for 3-7-week-old hamsters were derived from
      tumours formed in animals inoculated within 5 days of birth. The cells contained
      HPV 16 DNA in an integrated form and HPV16 transcripts. The transcript patterns
      in low and high oncogenicity sublines were different. Very few tumour-bearing
      animals possessed antibodies reactive with E6- and E7-derived synthetic peptides.
      On the other hand a majority of these animals gave a positive reaction in the
      lymphoproliferation assay with either E6 and E7 peptides or extracts from the
      transformed cells.

PMID- 9171457
TI  - Monoclonal antibodies against potato virus A -- immunoblot analysis.
AB  - Monoclonal antibodies (MoAbs) against potato virus A (PVA) were examined in their
      reactivity with PVA and its denatured capsid protein (PVA-CP) bound to the
      nitrocellulose membrane. Five MoAbs reacted with native PVA, three of them also
      with PVA-CP. One MoAb gave no reaction in dot-blot test. In polyacrylamide
      electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE) PVA-CP
      migrated as two major bands. In immunoblot analysis, two MoAbs reacted only with
      the slower band, one only with the faster one. We presume that those bands do not
      correspond to the intact CP but they do to truncated N- and C-terminal CP
      molecules, respectively, and that the corresponding epitopes reacting with MoAbs
      are localized near to both termini of CP molecules. After mild trypsinolysis of
      PVA particles no MoAb reacted with resulting "core" CP.

PMID- 9171458
TI  - Materno-umbilical ratio of hepatitis B virus (HBV) surface antigen exceeds that
      of human chorionic gonadotropin in HBV-infected deliveries.
AB  - Low levels of HBV surface antigen (HBsAg) are commonly present in umbilical blood
      from neonates born to chronically infected mothers, but the origin and clinical
      significance of umbilical antigenemia is not clear. The present study was
      undertaken to investigate whether the umbilical HBs-antigenemia is linked to a
      demonstrable level of admixture with maternal blood, as evaluated by the
      assessment of the maternal-umbilical (M/U) ratio of human chorionic gonadotropin
      (hCG). The latter has a steep gradient across the placenta and is currently used
      as the most sensitive maternal marker in foetal sampling procedures. HBsAg and
      hCG were assayed in 6 paired maternal-umbilical serum samples from Kenya. In 3
      cases with umbilical serum testing slightly positive for HBsAg, the M/U ratio of
      the antigen was around 8,000, or more than ten times the M/U ratio of hCG. In
      conclusion, the assessment of hCG in umbilical blood does not reveal the origin
      of umbilical HBsAg, unless the sample is grossly contaminated with maternal
      blood.

PMID- 9171459
TI  - Chronic infection of Balb/c mice with murine herpesvirus 72 is associated with
      neoplasm development.
AB  - One hundred Balb/c mice were infected with murine herpesvirus strain 72 (MHV-72)
      and observed for 2.5 years for neoplasm development and virus presence in tumour
      as well as non-tumour tissues. Out of 13 neoplasm-bearing mice the virus was
      recovered from solid tumours (one lymphoma, two non-differentiated
      lymphoblastomas and two fibrosarcomas) of five mice and from the spleen of one
      mouse with lymphatic leukemia. The virus persisted frequently also in various
      organs of the neoplasm-bearing mice.

PMID- 9171460
TI  - Envelope gene sequence variation among Japanese encephalitis viruses isolated in
      Korea.
AB  - The nucleotide (nt) sequences of the envelope (E) gene of 4 Japanese encephalitis
      virus (JEV) isolates from Korea (K82PO1, K87P39, K91P55 and K94PO5) were
      determined and the deduced amino acid (aa) sequences were compared within
      themselves and with the published sequences of 16 other JEV strains originating
      from other parts of Asia. Homologies of 87.2 - 95.6% at the nt level and 95.8 -
      98.0% at the aa level among the Korean JEV isolates were found. aa positions 89,
      129, 220, 225, 327, 366, 456 and 477 characterized the Korean isolates. According
      to the phylogenetic analysis based on the E gene nt sequence, the Korean isolates
      formed distinct subgroup consisting of at least 2 genetic types.

PMID- 9171461
TI  - Recombinant vaccinia virus expressing Pre-S/S protein of duck hepatitis B virus
      and its preliminary use for treatment of persistent infection.
AB  - The envelope (Pre-S/S) gene of duck hepatitis B virus (DHBV) was amplified by
      polymerase chain reaction (PCR) and cloned into plasmid pGJP5, under the control
      of vaccinia virus promoter P(7.5). By recombination in cell culture, and screened
      in human TK- 143 cells in the presence of 5-bromouracil deoxyriboside (5-BUdR), a
      recombinant vaccinia virus, bearing the envelope gene of DHBV (pGDHBV-5) which
      could replicate in cell cultures was constructed. DHBV surface antigen (DHBsAg)
      was detected in pGDHBV-5-infected cell lysate by dot enzyme immunoassay (EIA).
      After multiple-site intradermal injections of pGDHBV-5, DHBsAg could be detected
      in the serum of immunized adult ducks. This indicated that the recombinant virus
      replicated and expresed DHBsAg in ducks. The recombinant virus was used as a
      therapeutic vaccine to immunize persistently DHBV-infected ducks. After
      immunization, a transient significant decrease of serum DHBsAg was observed.

PMID- 9171462
TI  - Restriction endonuclease analysis of DNA from Indian isolates of bovine
      herpesvirus 1.
AB  - The genomic variation of three isolates of bovine herpes virus 1 (BHV-1)
      originating from different geographical regions and displaying different clinical
      symptoms were studied by restriction analysis using four different restriction
      endonucleases. EcoRI displayed an uniform restriction pattern for all the
      isolates and HindIII showed marginal variation among the isolates. BstEII and
      PstI displayed unique restriction patterns, based on which the isolates could be
      grouped into two subgroups of BHV-1.1. BstEII appears to be the enzyme of choice
      for differentiating BHV-1.1.

PMID- 9171463
TI  - Diving decompression fails to activate complement.
AB  - The present study evaluated complement activation during decompression after air
      dives in a hyperbaric chamber. Intravascular bubbles were quantified by Doppler
      ultrasound scoring. Eighteen subjects completed 92 dives, of which 74 produced
      bubbles. Complement activation was assessed by plasma C3a des Arg and red-cell
      bound C3d before and after each dive. These parameters of in vivo complement
      activation failed to show significant activation. In vitro complement activation
      susceptibility tests on pre-dive sera were performed to explore their association
      with in vivo complement activation and intravascular bubbles. Such tests failed
      to identify a distinct complement-sensitive group and did not correlate with in
      vivo complement activation during the dives and/or intravascular bubble
      appearance. Two subjects developed decompression sickness but were not different
      from the rest of the group regarding in vitro complement sensitivity or
      complement activation during dives.

PMID- 9171464
TI  - Exercise during decompression reduces the amount of venous gas emboli.
AB  - To determine the effects of moderate, intermittent exercise during decompression
      on the Doppler detectable amount of venous gas emboli (VGE), 29 healthy male
      volunteers performed 44 wet (8 degrees +/- 2 degrees C) dives to 45 msw (450 kPa)
      for 30 min with standard air decompression. During compression and the bottom
      period, all subjects were inactive; during decompression, 28 remained inactive,
      11 performed leg exercise, and 5 did arm exercise. Intermittent exercise was
      controlled at approximately 50% of each subject's arm or leg aerobic capacity. At
      30-min intervals after surfacing, subjects were monitored with a Doppler
      ultrasonic bubble detector. The Doppler scores were used to calculate the Kisman
      Integrated Severity Score (KISS). The KISS were log transformed (with zeroes
      being equivalent to log 0.01) and analyzed with a one-way analysis of variance.
      No significant differences (P < or = .05) between mean KISS scores after arm or
      leg exercise were observed, thus these data were pooled and compared to those of
      the inactive controls. The mean pooled KISS after exercising during decompression
      were significantly lower than those of the inactive controls. Moderate,
      intermittent exercise during decompression apparently reduces the amount of
      Doppler-detectable VGE after diving. The incidence rate of decompression sickness
      in both groups was not significantly different (P < 0.05).

PMID- 9171465
TI  - Doppler-echocardiography study of cardiac function during a 36 atm (3,650 kPa)
      human dive.
AB  - To determine the influence of a saturation dive on cardiac function, Doppler
      echocardiographic measurements were compared at sea level and during a 36 atm
      (3,650 kPa) He-O2 dive (gas density: 7 g/liter) in four healthy men. Left
      ventricular systolic function was studied from time motion measurements.
      Transmitral flow (E:A ratio) and isovolumetric relaxation time were used to
      assess left ventricular diastolic function. Cardiac output was derived from
      systolic pulmonary and aortic valvular flows. Cardiac output decreased 4.4 +/-
      0.8 vs. 5.9 +/- 1.2 liter/min at sea level) whereas stroke volume, left
      ventricular ejection fraction, atria and ventricular diameters remained
      unchanged. Thus, the decrease in cardiac output was attributed to bradycardia (56
      +/- 8 vs. 73 +/- 9 beats/min at sea level) which probably resulted from the
      slight hyperoxia (PI(O2), 0.4 atm). We found no evidence of left ventricular
      diastolic dysfunction. nor did we find valvular regurgitation or pulmonary
      hypertension. We conclude that Doppler-echocardiography can be used safely to
      investigate cardiac function during human saturation dives. Our results suggest
      that a 36 atm He-O2 dive does not modify cardiac or systolic and diastolic
      function except for a slight decrease in cardiac output correlated to
      bradycardia.

PMID- 9171466
TI  - Decompression sickness from saturation diving: a case control study of some
      diving exposure characteristics.
AB  - A comprehensive computerized database of diving activity for a Norwegian offshore
      diving contractor [Stolt-Nielsen Seaway (SNS)] covering the years 1983-1990 has
      been established. The database contains detailed dive information about 12,087
      surface-oriented and 2,622 saturation dives. During this period a majority of the
      divers were permanently employed. Preliminary analysis had suggested that
      decompression sickness (DCS) might be the result of exposure to factors causing
      pathophysiologic effects which accumulate over the course of a single dive or a
      series of dives. This concept evolved into the HADES (Highest Accumulated
      Decompression Score) theory which assumes that DCS is predictable once the
      underlying exposure factors are understood. The incidence of DCS among the SNS
      divers from saturation diving in the North Sea was studied by use of a "nested"
      case-control design. Twenty-one case dives (i.e., dives where DCS occurred) were
      compared with 41 randomly selected control dives. For these dives, several
      saturation dive characteristics were established. The relative pressure change
      between maximum and minimum storage depths was significantly greater among the
      cases. For each 1% increase in the relative pressure change there was a 5%
      increase in the probability of a saturation dive resulting in DCS. Significantly
      more cases than controls performed a saturation dive with more than one storage
      depth, and the data suggested that there were more and greater ascending and
      descending changes in storage depth conditions among the affected divers.

PMID- 9171467
TI  - Simulating respiratory loads and tuning of closed-circuit underwater breathing
      apparatus.
AB  - An experimental apparatus for simulating respiratory loads in closed-circuit
      underwater breathing systems comprises a partly submerged vertical tube having a
      dual path exit on the submerged end of the tube. One path is controlled by a
      valve that alters the inertance of the system, changes the natural frequency, and
      provides the tuning. The vertical tube provides elastic loading to simulate a
      counterlung or breathing bag in an underwater breathing apparatus (UBA). The
      experimental apparatus was connected to a breathing machine controlled by a
      signal generator to simulate a diver's breathing. The benefits of reactance
      tuning of this apparatus are demonstrated. A mathematical model describes both
      the simulator and UBA. The simulator can be used with human subjects to study
      respiratory response to changes in impedance.

PMID- 9171468
TI  - Diver respiratory responses to a tunable closed-circuit breathing apparatus.
AB  - Respiratory impedance of closed-circuit underwater breathing apparatus (UBA) is
      comprised of resistive, elastic, and inertial elements in series. Impedance is at
      a minimum when a UBA operates at its resonant frequency (f(n)). This study
      investigated the respiratory responses of 12 male U.S. Navy divers to changes in
      the f(n) of a simulated closed-circuit UBA. Respiratory effort, breathing comfort
      and ventilatory parameters were assessed during open- and closed-circuit
      breathing at rest and while exercising at 75 W on a bicycle ergometer in the dry
      at 1 atm abs. During closed-circuit breathing, the f(n) of the system was
      adjusted to different frequencies between 0.2 Hz and 0.4 Hz (12 and 24
      breaths/min) by varying UBA inertance. When the simulated UBA was switched from
      open to closed-circuit breathing the subjects changed their breathing frequency
      in a direction toward the f(n) of the system and attempted to maintain minute
      ventilation constant by adjusting tidal volume. Results suggest that when divers
      breathe on a closed-circuit system with different f(n)'s they attempt to improve
      breathing comfort and reduce respiratory effort by adopting a breathing pattern
      that reduces their peak-to-peak mouth pressures.

PMID- 9171469
TI  - Normobaric and hyperbaric oxygen treatment of acute carbon monoxide poisoning in
      rats.
AB  - Based on a model of acute carbon monoxide (CO) poisoning in rats with an occluded
      left carotid artery, we have evaluated the effects of normobaric oxygen (NBO2)
      and hyperbaric oxygen (HBO2) on mortality and morbidity. After exposure to 2,700
      ppm CO in air for 1 h, the rats were grouped and treated with air (group 1,
      untreated controls, in a previous study), 100 kPa O2 for 4 h (group 2), 300 kPa
      normoxia (group 3, pressure controls), and 300 kPa O2 (group 4) for 1 h,
      respectively. NBO2 started immediately, whereas HBO2 began 35 min after the end
      of the CO exposure. At the termination of the exposure, the four groups suffered
      identical levels of poisoning as indicated by the degrees of hypothermia,
      hypocapnia, drop in mean arterial pressure, and acidosis. Up to 48 h after the
      end of the CO exposure, mortalities were 76, 58, 75, and 17 in groups 1-4,
      respectively. The neurologic morbidities, indicated by abnormal motor behaviors
      and edema in the left cerebral hemispheres, were 84, 67, 83, and 42% in groups 1
      4, respectively. Compared to the normoxic treatments, the HBO2, but not the NBO2,
      significantly reduced the mortality and the neurologic morbidity. HBO2 was also
      significantly better than NBO2 in increasing surviving time and survival rate.
      The results support the value of HBO2 in improving short-term outcome of acute CO
      poisoning in this rat model.

PMID- 9171470
TI  - Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic
      pathways.
AB  - A controlled study was done with the aim of assessing the efficacy of hyperbaric
      oxygen (HBO2) in cluster headache and of studying the possible influence of this
      therapeutic approach on serotonergic pathways. Fourteen patients, aged between 26
      and 56 yr, suffering from the chronic form of cluster headache were treated with
      HBO2 (n = 10) or environmental air (placebo) ( n = 4) during the 15 sessions of
      exposure (lasting 30 min each) in the hyperbaric chamber. The influence of this
      procedure on serotonergic pathways of pain was monitored by means of study of
      serotonin binding to mononuclear cells before and after the treatment for both
      subgroups. All of the treated 14 chronic cluster headache patients completed the
      study. In the subgroup treated with the placebo, no particular modifications on
      the number of attacks and of analgesic consumption as well as no change in the
      specific binding curve of serotonin to mononuclear cells were observed, whereas
      in the subgroup treated with HBO2 the clinical effectiveness and the appearance
      of plateau in the binding curves indicated that the oxygen therapy could act
      through serotonergic pathways.

PMID- 9171471
TI  - Cell proliferative modulation of MCG 101 sarcoma from mice exposed to hyperbaric
      oxygenation.
AB  - Tumor cell kinetics were studied in C57 Bl/J mice with a transplantable sarcoma,
      MCG 101, exposed to hyperbaric oxygen (HBO2), 2.8 atm abs, 2 hours daily for 9
      days or until spontaneous death. The isoenzymatic pattern of lactate
      dehydrogenase (LDH) confirmed that there was a significant shift toward aerobic
      metabolism in tumor tissue as well as in the liver and skeletal muscle.
      Recruitment of cells from the G0G1 state into DNA synthesis was associated with
      an increased mobilization of substrates for polyamine synthesis in terms of an
      elevated ornithine decarboxylase (ODC) activity. However, cell cycle turnover in
      terms of bivariate flow cytometric analysis after bromodeoxyuridine (BrdUrd)
      injection, final tumor weight, and survival time were not changed compared with
      the controls. Tumor cell metabolism demonstrated evidence of an unchanged net
      energy utilization, in that activities (V(max) of phosphofructokinase (PFK) and
      LDH were not significantly changed. When the tumor-bearing animals were exposed
      to advanced HBO2 pressure (3.7 atm abs) for 3 h as a single dose, the DNA
      distribution and growth rate were not changed immediately. However, 3.5 h later
      we observed a DNA pattern similar to that after repeated HBO2 treatments, 2.8 atm
      abs, concomitant with a preponderance of cells in the late S-phase, which is
      consistent with a block at the entry of G2M. We conclude that MCG 101 sarcoma
      recovers from HBO2 exposure by an accumulation of cells in the S-phase without
      significant changes of net tumor growth. This may have relevance to clinical
      radiocurability.

PMID- 9171472
TI  - Ocular quinine toxicity treated with hyperbaric oxygen.
AB  - Ocular quinine toxicity typically involves a partial or total and often permanent
      loss of vision. Apart from gastric lavage and oral administration of activated
      charcoal, current treatment modalities are of doubtful efficacy. Two patients
      with quinine amaurosis were treated with hyperbaric oxygen (HBO2) in an effort to
      increase oxygen delivery to the retina. Visual outcomes in these patients were
      evaluated. Two patients had bilateral no light perception vision and dilated,
      nonreactive pupils within hours of ingesting 13-15 g of quinine in addition to
      other drugs. Following initial oral charcoal administration, HBO2 therapy was
      used. Within 17 h after quinine ingestion, both patients underwent HBO2 therapy
      at 2.4 atm abs with 100% O2 for 90 min. Both patients had return of visual acuity
      to 20/20 in both eyes less than 24 h after treatment. Follow-up visual fields
      revealed constriction and paracentral scotomas bilaterally. We conclude that HBO2
      may represent an additional or alternative, and perhaps safer, method of
      treatment for ocular quinine toxicity.

PMID- 9171473
TI  - General Dentistry's peer review process.

PMID- 9171474
TI  - The ethical foundations of a duty to treat HIV-positive patients.
AB  - Unfortunately, those who commit the most egregious acts of HIV-related
      discrimination may not be motivated to change either by fines and sanctions, or
      by educational programs. Perhaps the best solution to dealing with the small, but
      significant, number of health care providers who discriminate against HIV
      positive patients is the action of the majority. Most dentists are ethical and
      concerned health care professionals, who willingly care for patients with a wide
      array of medical problems. This majority must continue to serve as an example to
      those who refuse to care for HIV-positive patients, and must make it clear that
      such actions are professionally intolerable.

PMID- 9171475
TI  - New antidepressant medications.

PMID- 9171476
TI  - Reducing the failure potential of ceramic-based restorations. Part 2: Ceramic
      inlays, crowns, veneers, and bridges.

PMID- 9171477
TI  - Efficient endodontic access: rapid pulpotomy with a safe-ended diamond.
AB  - A correct access opening is the key to endodontics. An adequate anatomical access
      preparation maximizes cleaning, shaping, and obturation. The major objectives of
      access preparation are straight line access to the apical area, conservation of
      tooth structure, and unroofing of the pulp chamber. The safe-ended diamond bur
      technique provides an efficient and rapid means to obtain the objective of access
      preparation in posterior teeth.

PMID- 9171479
TI  - Thermafil obturation: a literature review.
AB  - A review of the literature pertaining to the use of Thermafil Endodontic
      Obturators is presented in this article. Addressed are such concerns as apical
      microleakage, biocompatibility, coronal leakage, post space considerations,
      retreatment issues, surgical factors, and clinical evaluations of Thermafil;
      included are the authors' conclusions concerning its clinical use.

PMID- 9171478
TI  - Root resorption: types and treatment.
AB  - Root resorption is a challenging problem for dental practitioners. This paper
      presents a simple, organized classification of the types of root resorption and a
      discussion of the clinical and radiographic features of each. Treatment
      requirements or options are given, along with prognosis relative to the type of
      resorptive defects. Knowledge of these entities and of the modalities of
      treatment for each can assist the dentist in providing the appropriate care to
      maximize retention of these affected teeth.

PMID- 9171480
TI  - Dental professional's role in diagnosing Sjogren's syndrome.
AB  - In this investigation, a written questionnaire was used to assess patient's
      perceptions of health care professionals' knowledge about Sjogren's syndrome.
      Results show that dental and other health care professionals need to be better
      informed about the nature of Sjogren's and its symptoms so they can diagnose
      patients. Early diagnosis may help mollify symptoms and reduce anxiety or other
      perceived harmful consequences.

PMID- 9171482
TI  - Odontogenic infection mimicking antral polyps.
AB  - Odontogenic infections can extend into the maxillary sinus and produce sinusitis
      that mimics other pathoses. Infection of odontogenic origin should be considered
      in the differential diagnosis of maxillary sinusitis. Sinusitis should be
      considered in the differential diagnosis of maxillary posterior teeth with acute
      or chronic symptoms.

PMID- 9171481
TI  - Rapidly progressing extracanal invasive resorption.
AB  - Frank and Bakland coined the term "Extracanal invasive resorption" (EIR) to
      identify a resorptive entity that has been variously classified. This external
      resorption originates in the cementum adjacent to the periodontal ligament. The
      lesion is believed to be a response to injury and irritation of the periodontal
      ligament, or to pressure from ectopic eruption, orthodontic pressure,
      intracoronal bleaching, periodontal treatment, or an unknown idiopathic cause.

PMID- 9171483
TI  - Curing lights: changes in intensity output with use over time.
AB  - Intensity output of curing lights affects cure depth and time needed for complete
      polymerization of resin composites. In this study, changes in intensity output of
      Max Curing Lights (L.D. Caulk Co., Milford, DE) were compared over time. With a
      Demetron Model 100 Curing Radiometer (Demetron Research Corp., Danbury, CT), 201
      curing lights (from 1 to 3 years old) were tested. The 1- and 2-year-old lights
      had mean outputs of 423 mW/cm2; the 3-year-old lights had a mean output of 376
      mW/cm2. An analysis of variance (ANOVA) and post-hoc Scheffe test demonstrated a
      significant effect of use over time on intensity output of these lights.

PMID- 9171484
TI  - Osteitis in a torus mandibularis secondary to trauma.
AB  - A case is reported of osteitis in a mandibular torus subsequent to trauma, and
      the literature is reviewed. Excision of a torus mandibularis is recommended once
      osteitis develops.

PMID- 9171485
TI  - Confidentiality versus disclosure of a patient's infectious status.
AB  - Patients in health care settings have a legal and moral right to privacy, which
      includes confidentiality of all information related to the patient or gathered by
      the patient's health care team. Even so, the right to privacy is not total. Under
      certain circumstances, that right must yield to a state's fundamental right to
      enact laws to promote public health and to ensure public safety and welfare.
      Justifiably, dental health care team members are concerned with their health and
      with the possibility of being infected by a fatal disease such as acquired
      immunodeficiency syndrome (AIDS). The right to know patients' infectious status
      is growing with the mortality rate of the disease. However, as more health care
      workers learn of a patient's infectious status, that patient's privacy
      diminishes. Abiding by laws that enforce doctor-patient confidentiality while
      still fulfilling their obligations to their staffs and related third parties
      often proves difficult for dentists and physicians. Since the discovery of AIDS,
      believed to be caused by the human immunodeficiency virus (HIV), health care
      providers have been increasingly conscientious in maintaining these professional
      relationships.

PMID- 9171486
TI  - Nitrous-oxide use. II. Risks, compliance, and exposure levels among Nebraska
      dentists and dental assistants.
AB  - This study measured nitrous oxide (N2O) exposure levels of 70 dentists and their
      dental assistants, and related these results to minutes of N2O use, compliance
      with N2O use guidelines, and risk of exposure. Dentists and dental assistants
      averaged, respectively, 97 and 59 parts per million (ppm) in N2O exposure, much
      higher than the recommended 25 to 50 ppm. Estimated peaks of exposure averaged
      1,415 and 986 respectively for the two groups. Dentists exposure levels were
      significantly higher than those of dental assistants in both measures.
      Correlations revealed a significant link between compliance and estimated maximum
      exposure, and between minutes of use and 40-hour exposure readings. The variables
      most predictive of 40-hour N2O exposure were: minutes of use, frequency of use,
      number of operatories equipped, education of staff members on N2O health risks
      and exposure control, and operation of scavenging systems with the recommended
      liters/minute. This study established a feasible methodology for long-term, field
      based epidemiological studies on N2O exposure, and identified some key variables
      related to 40-hour exposures and estimated maximum exposure.

PMID- 9171487
TI  - Taking advantage of the data deluge.

PMID- 9171488
TI  - The effect of eliminating implant/abutment rotational misfit on screw joint
      stability.
AB  - External hexagonal implants of known dimensions were assembled with premachined
      cast abutments and rebroached cast abutments. The abutment screws were tightened
      to 20 Ncm and 30 Ncm, and the samples were loaded off axis with 133.3 N. Load
      application was at 1,150 cycles per minute with a sample counterclockwise
      rotation of 28 cycles per minute. The premachined cast abutments tightened to 20
      Ncm failed with a mean of 357,162 cycles (SD = 77,981 cycles). The rebroached
      cast abutments were cycled to 1 million cycles without failure. At 30 Ncm, the
      premachined cast abutments failed at a mean of 5.0 million cycles (SD = 2.2 X
      10(6) cycles). Two of five rebroached cast abutments failed at 4.3 million and
      9.5 million cycles, but the remaining samples showed no evidence of screw
      loosening after 10 million cycles, at which time the test was terminated. The
      results indicate a direct correlation between rotational misfit and screw
      loosening. Screw joints can be made more resistive to screw loosening by the
      elimination of rotational misfit.

PMID- 9171489
TI  - Thickness and accuracy of superplastic Ti-6Al-4V alloy denture frameworks.
AB  - The thickness and adaptation of superplastic forming Ti-6Al-4V alloy denture
      frameworks were investigated using cross-sectional measurements. The frameworks
      for maxillary complete dentures were fabricated form Ti-6Al-4V disks of thickness
      ranging from 0.75 to 1.30 mm. Although the thickness of each disk was reduced by
      superplastic forming, the complete framework had more than 78% of the original
      disk thickness. Differences in the thickness did not significantly affect either
      the thickness ratio of the framework to the disk or the gap discrepancy between
      the framework and the working cast. The accuracy of fit of the framework would
      satisfy ordinary clinical requirements.

PMID- 9171490
TI  - Effects of cobalt-chromium alloy surface casting on resistance to deflection
      fatigue and surface hardness of titanium.
AB  - This study investigated the resistance to deflection fatigue and surface hardness
      of grade 2 titanium bar samples to a portion of which a layer of cobalt-chromium
      alloy was cast under standard dental laboratory conditions. The uncovered part of
      the titanium bar was deflected, and the number of loading cycles required to
      cause a fatigue fracture in the titanium bar was recorded. The Vickers hardness
      of the titanium bar was measured, and the fracture surface was examined by
      scanning electron microscope and energy-dispersive spectroscopy. The number of
      loading cycles was considerably lower in bars with the cobalt-chromium surface
      cast (83 vs. 13.770 cycles) (P < .001), while the surface hardness of the
      titanium bar with the cobalt-chromium surface cast was higher than that without
      the surface cast (Vickers hardness number 329 vs. 178) (P < .001). These findings
      suggest that the cobalt-chromium surface cast dramatically affects the fatigue
      resistance of pure titanium, which should be considered when novel implant
      supported prostheses made from premanufactured titanium parts are planned.

PMID- 9171491
TI  - Long-term clinical results after treatment with conical crown-retained dentures.
AB  - The clinical outcome of treatment using conical crown-retained dentures was
      evaluated. Of the initial 25 patients provided with 26 conical crown-retained
      dentures, 18 patients with 18 restorations could be examined after a time ranging
      between 73 and 92 months. Of the eight restorations lost, four had been changed
      as a result of factors that might have been related to the prosthodontic care.
      Most of the patients were very satisfied with the restorations both functionally
      and esthetically and found their chewing comfort to be better after treatment
      with conical crown-retained dentures. However, 50% of the patients reported
      speech problems related to treatment. Technical failures were not insignificant
      but were treatable. The survival rate after 73 to 92 months was 78.3%.

PMID- 9171492
TI  - Changes of masticatory movement characteristics after prosthodontic
      rehabilitation of individuals with extensive tooth wear.
AB  - The masticatory cycles of 11 men (mean age 51.5 years) with extensive tooth wear
      were investigated before and after rehabilitation with fixed partial dentures.
      Parameters such as the tooth wear index (IA) and masticatory mandibular movement
      were recorded. Before treatment, the patients were also given a questionnaire
      related to possible background factors of importance to tooth wear. At baseline a
      mean score of 48.6 (range 0 to 100) for the tooth wear index (IA) was found. The
      clinical recall examination 3 years after prosthodontic rehabilitation displayed
      obvious wear of restorative material for two patients, and, in another patient,
      one of the fixed partial dentures had to be remade because of fracture of
      abutment teeth. Following rehabilitation, the duration of the masticatory
      mandibular opening movement increased and mandibular movement velocity decreased.
      The mandibular closing angle, near to occlusal contact, became steeper after
      prosthodontic treatment, indicating a changed mandibular movement pattern.

PMID- 9171493
TI  - Effect of three variables on the accuracy and variability of electroplated copper
      dies.
AB  - This investigation compared the accuracy of electroplated copper and stone dies.
      Sixty copper die replicas of a stainless steel master die were fabricated using
      different current settings, plating times, and backing materials. Die accuracy
      was assessed by measuring the misfit of a stainless steel ring machined to fit
      the master die. All the copper dies were more accurate than the 10 stone dies.
      The variability of the copper/stone dies was less than that of the stone dies (P
      = .011) and copper-resin dies (P < .001). There was no significant difference
      between the variability of the 40-mA, 48-hour copper-resin dies and the stone
      dies. The variability of the copper-resin dies was related to the thickness of
      the electrodeposit, which was a function of plating time, current, and plated
      surface area.

PMID- 9171494
TI  - Shear bond strength of Rexillium III to enamel using resin composite cements.
AB  - This study evaluated the shear bond strength of Rexillium III (Jeneric Pentron,
      Wallingford, CT) to enamel using various resin composite luting systems. Cast
      alloy cylinders (3.9 mm X 6.0 mm) were bonded with each cement to human molar
      buccal enamel surfaces (n = 8). The enamel was etched using a 35% phosphoric acid
      solution for 30 seconds. Bonded specimens were stored in distilled water for 7
      days at 37 degrees C and thermocycled (1,500 cycles) in 5 degrees C and 55
      degrees C water baths (1-minute dwell time). Specimens were randomly tested in
      shear using a crosshead speed of 0.5 mm per minute. Use of a one-way analysis of
      variance (P < .001) and Ryan-Einot-Gabriel-Welsh multiple range test showed
      significant differences between several of the resin cements. Panavia exhibited a
      significantly higher shear bond strength than any of the other cements tested.

PMID- 9171495
TI  - The physical properties of low-fusing porcelains for titanium.
AB  - This study compared the firing shrinkages, flexural strengths, and chemical
      solubilities of two low-fusing porcelains formulated for use with titanium
      (Procera, Nobel Biocare, Goteborg, Sweden; and Duceratin, Degussa, Plainfield,
      NJ) to those of a conventional low-fusing feldspathic porcelain (Vita VMK 68,
      Vident, Baldwin Park, CA). Procera demonstrated the highest mean firing shrinkage
      and was significantly different from the other two porcelains. There were no
      significant differences among the porcelains in flexural strength and chemical
      solubility.

PMID- 9171496
TI  - The surface of investments poured against different duplicating media.
AB  - Two phosphate-bonded investments that were poured into molds of a duplicating gel
      and a poly(vinyl siloxane) duplicating medium were examined for surface hardness.
      Untreated surfaces were also examined by the confocal microscope and the scanning
      electron microscope. The Brinell hardness of samples poured in poly(vinyl
      siloxane) was greater than that of the same investment poured in duplicating gel.
      Investments were hardest as set and were significantly softened by drying. Cast
      hardeners achieved some rehardening of the dried investment samples. Microscopic
      examination of the investment surfaces revealed greater irregularity of samples
      poured in duplicating gel than in poly(vinyl siloxane), particularly in one
      investment.

PMID- 9171498
TI  - The accuracy of implant verification casts compared with casts produced from a
      rigid transfer coping technique.
AB  - PURPOSE: Prosthodontic techniques for implant-supported prostheses continue to
      evolve in an effort to facilitate treatment and minimize costs. Because research
      has shown no impression transfer technique to be without error, some clinicians
      have attempted to control the fit of prosthetic frameworks by reorienting
      sections of patterns or frameworks intraorally, fabricating a verification cast,
      and completing the prosthesis to fit such a cast. One manufacturer has attempted
      to meet both impression-making and verification-cast objectives by providing
      metallic impression copings (MICS) with extensions that allow contact between the
      copings for rigid fixation with acrylic resin before impression making. The
      purpose of this study was to determine the accuracy of casts produced from the
      MICS transfer process compared with casts produced from sectioned frameworks,
      where both techniques used a low-polymerization-shrinkage acrylic resin polymer
      to rigidly join the sections. MATERIALS AND METHODS: Using stainless steel
      measurement spheres as a reference point on each implant analog, the distances
      between analogs on the experimental casts were compared with the distances
      measured on the master cast. Seven casts were produced for each group and
      measured with a machinist's microscope at a 4-micron level of precision. RESULTS:
      The results revealed that the MICS transfer exhibited a mean error of 41 microns,
      which was significantly less than the verification-cast group mean error of 57
      microns (p < .01, Student's t test). CONCLUSIONS: Given these results, clinicians
      can consider the rigid transfer technique as provided in the MICS transfer to be
      more accurate than the verification technique as outlined in this study.

PMID- 9171497
TI  - Fracture resistance of human enamel and three all-ceramic crown systems on
      extracted teeth.
AB  - This in vitro study measured the fracture resistance of intact extracted molars
      and three types of all-ceramic crowns; feldspathic porcelain, glass-ceramic, and
      glass-infiltrated alumina. All crowns were of a simplified three-cusp occlusal
      configuration, and were placed on prepared, extracted third molars. The ceramic
      crowns were bonded to dentin with a resin composite cement, except for 10 of the
      feldspathic crowns, which were luted with zinc phosphate cement. The fracture
      resistances was measured using a spherical steel indenter that contacted the
      occlusal surface at three points. A total of 40 ceramic crowns and 50 extracted
      maxillary third molars were tested. The Weibull distribution was used for data
      analysis. Intact extracted teeth were significantly stronger than all-ceramic
      crowns. Of the ceramic restorations, the glass-infiltrated alumina crowns
      exhibited the highest fracture resistance.

PMID- 9171499
TI  - Fatigue of resin cement-base metal alloy bond strength.
AB  - PURPOSE: Strong durable bonds between resin cements and metal alloys are critical
      to the success of resin-bonded, resin-veneered, or resin-retained prostheses.
      However, few comprehensive, comparative evaluations of materials or the fatigue
      effects of thermal cycling have been reported. The rate of strength loss may be a
      more important predictor of long-term success than bond strength. The purpose of
      this study was to investigate the effects of artificial aging by thermal cycling
      and resin cement type on the bond strengths to a base metal alloy. MATERIAL AND
      METHODS: This study investigated the effect of the number of thermal cycles (0,
      1, 10, 100, 1,000, and 10,000) on the bond strengths of nine fixed prosthodontic
      resin cements. Specimens were assigned randomly to thermal cycle number/cement
      type test groups. Cylinders of a base metal alloy were bonded in an end-to-end
      configuration. One end of each bonded specimen was insulated, and the specimen
      was thermal cycled. Then, the bonds were tested in shear and bond strengths
      calculated. RESULTS: Two-way ANOVA revealed that the effects of cement type, the
      number of thermal cycles, and their interaction all significantly affected bond
      strength (p < .0001). Multiple range analysis showed that some cements had
      significant trends to lose bond strength with thermal cycling (p < .05), while
      others did not (p > .05). CONCLUSIONS: Both the type of resin cement and the
      amount of thermal cycling influenced bond strength to a base metal alloy. Some
      materials displayed more rapid loss of bond strength than others.

PMID- 9171500
TI  - An evaluation of microwave-polymerized resin bases for removable partial
      dentures.
AB  - PURPOSE: The hardness, porosity, and adaptation of removable partial dentures
      fabricated with one heat-polymerized denture base resin and two resins designed
      for microwave polymerization were evaluated. MATERIALS AND METHODS: Five
      prostheses were evaluated for each resin. Adaptation of the denture bases to the
      master cast was evaluated by spatial orientation and mean weight of residual
      impression material. The prostheses were than embedded in epoxy resin and
      sectioned for evaluation of resin hardness (Knoop hardness) and microporosity.
      RESULTS: There were no significant differences in the adaptation of the acrylic
      resin bases for Acron MC and Ch Lucitone. There was no significant difference in
      the mean Knoop hardness values for any of the resin bases near and away from the
      metal. None of the denture bases showed porosity greater than 100 microns.
      CONCLUSIONS: Both resin bases formulated for microwave polymerization were
      effectively polymerized around metal frameworks without adverse effects on resin
      hardness or porosity. Justi Denture Base material had poorer base adaptation than
      the other two resins.

PMID- 9171501
TI  - Color stability of heat-activated and chemically activated fluid resin acrylics.
AB  - PURPOSE: Heat- and chemically activated acrylics processed by compression molding
      or fluid resin matrix techniques for fabrication of partial dentures were
      evaluated for color stability by reflection spectrophotometry after accelerated
      aging. MATERIALS AND METHODS: Samples of heat-activated (L199, PDON, SB) and
      chemically activated (PR, PVAR, SC) denture base acrylics were polymerized
      according to manufacturers' instructions. Samples were aged in an artificial
      aging chamber, and color was measured by CIE L*a*b* on a reflection
      spectrophotometer at baseline and after each of three aging cycles. RESULTS: At
      450 kJ/m2, color changes of two chemically activated acrylics (PR and SC) were
      perceptible. PR became less red, whereas SC became darker and more yellow. The
      most color-stable acrylics were a heat-activated resin (SB) and one chemically
      activated acrylic (PVAR). CONCLUSIONS: The three heat-activated acrylics tested
      were more color-stable than two of the chemically activated acrylics, but one
      chemically activated acrylic (PVAR) recommended for a fluid resin matrix
      technique was color-stable.

PMID- 9171502
TI  - A review of fiber-reinforced denture base resins.
AB  - PURPOSE: One method of reinforcing denture base material is to use fiber
      composite reinforcement. Different types of fibers, such as glass (GF),
      carbon/graphite, aramid, and ultrahigh-modulus polyethylene (UHMP) fibers have
      been tested for this purpose. MATERIALS AND METHODS: This article reviews the
      studies conducted on the fiber-reinforced denture base resin systems. RESULTS:
      The literature has reported that the fiber concentration and its adhesion to
      polymer matrix influences the transverse strength of the fiber composite. The
      highest transverse strength value (265 MPa) with polymethyl methacrylate (PMMA)
      was obtained by incorporating 58 wt% GF into the resin. UHMP fibers incorporated
      into PMMA resin yielded the highest impact strength value (134 kJm-2) of the
      fiber-PMMA composites. CONCLUSIONS: Despite the improved mechanical properties of
      fiber-reinforced denture materials, further research is required to show the
      clinical usefulness of the fiber reinforcement.

PMID- 9171503
TI  - Short-term results of IPS-Empress inlays and onlays.
AB  - PURPOSE: A leucite-reinforced, glass-ceramic material was recently introduced for
      clinical use. In this clinical trial, IPS-Empress inlays and onlays were
      evaluated using the modified United States Public Health Service (USPHS)
      criteria. MATERIALS AND METHODS: The teeth of 36 patients were restored with 105
      posterior inlays and 25 onlays, fabricated by an indirect technique. After
      etching the restorations with hydrofluoric acid, they were silanized and luted
      using composite cements. The restorations were evaluated visually, clinically
      with a mirror and probe, and by bitewing radiographs and clinical photographs,
      using modified USPHS criteria. Restorations having neither charlie nor delta
      criteria were defined as successful, and their survival rate was calculated
      according to Kaplan-Meier analysis. RESULTS: The mean observation period for the
      130 restorations was 23.4 +/- 6.1 months. After 2 years, 127 restorations were
      successful with an estimated survival rate of 97.5%. Three restorations failed
      because of fractures. The esthetic results were excellent. CONCLUSIONS: The
      initial clinical results of this esthetic restorative material are encouraging.
      However, because of fatigue phenomena for all ceramic materials, a longer
      observation period is needed to provide a definitive prognosis of the long-term
      clinical behavior.

PMID- 9171504
TI  - Metallurgical structure and microhardness of four new palladium-based alloys.
AB  - PURPOSE: This investigation compared the Vickers hardness and microstructures of
      four recently marketed, palladium-based alloys for metal-ceramic restorations.
      MATERIALS AND METHODS: Wax patterns simulating copings for maxillary central
      incisors were invested in a fine-grained, carbon-free, phosphate-bonded
      investment. Following burnout, the palladium alloys were fused with a gas-oxygen
      torch, centrifugally cast, and bench-cooled. Representative castings were
      embedded in transparent metallographic resin and sectioned to yield two mirror
      image specimens. The specimens were evaluated in either the as-cast condition or
      following heat treatment simulating the firing cycles for Vita VMK porcelain.
      Vickers hardness measurements (n = 50) were made using a 1-kg load, and
      photomicrographs of polished and etched specimens were obtained with a scanning
      electron microscope. RESULTS: The measured values of microhardness for the as
      cast alloys were in excellent agreement with values reported by the manufacturer.
      The hardness in the as-cast condition was significantly greater for the Pd-Cu-Ga
      In alloy, compared with the other three alloys, which did not contain copper. For
      the three high-palladium (> or = 75 wt%) alloys, there were small (4%-8%)
      decreases in hardness following heat treatment, whereas a larger decrease (13%)
      in hardness occurred for the Pd-Ag-In-Sn alloy after heat treatment. The
      porcelain firing cycles caused microstructural homogenization for all four
      alloys, and the relatively thick near-surface oxidation region in the Pd-Cu-Ga-In
      and Pd-Ag-In-Sn alloys was not observed in the two heat-treated Pd-Ga-Ag-In-Au
      alloys. CONCLUSIONS: The multiphasic microstructures of these alloys may have
      some significance for the in vitro and clinical corrosion behavior and the metal
      ceramic bond strength. The hardness for the three high-palladium alloys may be
      controlled by submicroscopic precipitates that remain unaltered by heat
      treatment. The significantly greater hardness for the Pd-Cu-Ga-In alloy may cause
      greater difficulty for finishing castings in the dental laboratory compared with
      the other three alloys studied. The strengthening mechanism for the Pd-Ag-In-Sn
      alloy has significant temperature dependence, which might be exploited to achieve
      optimum mechanical properties.

PMID- 9171505
TI  - The bond strength of an adhesive resin luting cement to a variety of surface
      treatments of a high-palladium copper alloy.
AB  - PURPOSE: This study evaluated the tensile bond strength of a bisphenol glycidyl
      methacrylate (Bis-GMA) resin luting cement with four different surface treatments
      of a high Pd-Cu alloy. MATERIALS AND METHODS: For each surface treatment type
      (tin-plated, porcelain furnace oxide, air-abraded, and finished-only), 15
      opposing half-dumbbell-shaped samples were cast and prepared in new Pd-Cu alloy.
      Samples were luted with a Bis-GMA resin luting cement at a film thickness of 80
      microns using a custom alignment apparatus. Samples were stored in distilled
      water at 37 degrees C for 24 hours, thermocycled for 1,000 cycles, and then
      stored for 30 days in distilled water at 37 degrees C. Samples were then
      subjected to fracture in tension at a loading rate of 0.5 cm/min with the bond
      strengths calculated in megapascals (MPa). The fractured surfaces were examined
      using stereomicroscopy and scanning electron microscopy at various magnifications
      ranging from 5.5x to 500x to determine the type of bond failure (adhesive,
      cohesive, or mixed). RESULTS: Tensile bond strengths (mean +/- SD MPa) were: tin
      plated, 30 +/- 15.7; porcelain furnace oxide, 23 +/-n 8.6; air-abraded, 8 +/-
      8.1; and finished-only, 4 +/- 4.5. Statistical analysis of the tensile bond
      values using an ANCOVA and Tukey's multiple comparison test at a significance
      level of 0.05 indicated that there was no difference between the tin-plated and
      the furnace oxide groups, as well as between the air-abraded and the furnace
      oxide groups. However, there was significant difference between the tin-plated,
      the air-abraded, and the finished-only groups. The observed bond failures were
      predominantly mixed and cohesive in nature with only one adhesive failure.
      CONCLUSIONS: There was no significant difference in the tensile bond strengths
      between the tin-plated group or the porcelain furnace oxide surface group. This
      suggests that the less-technique-sensitive porcelain furnace oxide surface
      treatment offers an alternative for achieving high metal-resin bonds to a high Pd
      Cu alloy.

PMID- 9171506
TI  - Fabricating low-fusing metal casts for more accurate implant prosthodontics.
AB  - An important factor that affects the clinical success of dental implants is the
      way stresses are transferred to the bone via the implant framework and fixture.
      An ill-fitting implant framework will contribute to these stresses and may result
      in catastrophic failure of the prosthesis or one of the components and/or
      fixtures, in addition to possible alveolar bone loss. Many factors may contribute
      to the difficulty of achieving a passive fit on a complete-arch implant
      framework. A technique for producing an accurate master cast by using a low
      fusing metal is described. The low-fusing metal is dimensionally more accurate
      than conventional gypsum products. The technique does not require a significant
      change from conventional chairside and laboratory procedures for complete-arch
      master cast impressions, and should result in a more passively fitting framework.

PMID- 9171507
TI  - Expression of CD1a monocytes cultured with supernatants from periodontally
      diseased gingival epithelial cells.
AB  - Langerhans cells are believed to originate from the monocyte lineage and have
      been reported to increase in number with plaque accumulation and gingival
      inflammation. The aim of this study was to investigate the effects of local
      gingival epithelial factors on the induction of CD1a, a Langerhans cell
      phenotype, on monocyte rich populations. MATERIALS AND METHODS: Peripheral blood
      monocyte rich in populations from healthy subjects were cultured for 24 h with
      either healthy gingival or periodontally diseased gingival epithelial
      supernatants. Additionally, the monocyte rich populations were cultured with
      cytokines IL-I alpha, IL-I beta, IL-6 and TNF-alpha which are known to be
      produced by epithelial cells or co-cultured with autologous epithelial cells. The
      per cent CD1a positive cells was determined using FACS analysis. RESULTS: Healthy
      gingival supernatants did not induce CD1a expression in monocyte rich
      populations, however, a significant increase in per cent CD1a+ cells for monocyte
      rich populations cultured with five (P < 0.01) of six periodontal gingival
      epithelial supernatants was found. IL-I alpha or TNF-alpha (10 ng/well) resulted
      in a significant increase in the per cent CD1a+ cells (P < 0.01). Depletion of
      CD1a+ Langerhans cells from healthy gingival epithelium did not enhance induction
      of CD1a expression in monocyte rich populations. Monocyte rich populations
      cultured together with non-depleted epithelial cultures resulted in a decreased
      per cent of CD1a+ cells. CONCLUSION: These findings indicated that epithelial
      factor/s associated with periodontally involved epithelia, may be involved in
      inducing a Langerhans cell phenotype in monocyte rich populations. The data also
      provide indirect evidence for a role of Langerhans cells in inhibiting induction
      of CD1a in healthy epithelium.

PMID- 9171508
TI  - Rheumatoid factor from periodontitis patients cross-reacts with epitopes on oral
      bacteria.
AB  - OBJECTIVES: The objective of this study was to determine the antigenic
      specificity of rheumatoid factor (RF) that had previously been reported in the
      serum of patients with periodontitis. DESIGN: IgM-RF was isolated from the serum
      of five RF-seropositive rheumatoid arthritis patients and 14 RF-seropositive
      periodontitis and examined for specificity to human IgG and selected oral
      bacteria. METHODS: IgM-RF was prepared by affinity chromatography on human IgG
      columns. Human IgG antibody to Capnocytophaga gingivalis, Fusobacterium
      nucleatum, and Actinobacillus actinomycetemcomitans was isolated by binding and
      elution of antibody from the bacteria, followed by purification using a rabbit
      anti-IgG affinity column. MAIN OUTCOME MEASURE: Binding of the isolated IgM-RF
      was determined using an enzyme-linked immunosorbent assay (ELISA). The antigens
      used for detection of binding included isolated human IgG, human IgG antibody
      bound to the bacteria, and the bacteria alone. Inhibition of the IgM-RF binding
      with IgG or Fc gamma was used to assess the specificity of the reactivity with
      IgG and/or the bacteria. RESULTS: The results showed that the IgM-RF reacted with
      polyclonal human IgG nonspecifically bound to microtiter plates. The reactivity
      of the IgM-RF was increased when incubated with IgG that bound as antibody to C.
      gingivalis, F. nucleatum or A. actinomycetemcomitans. However, the IgM-RF did not
      bind with increased intensity to the specific IgG antibody preparations or to IgG
      preparations lacking antibody to these micro-organisms. Additionally, the IgM-RF
      preparations bound to surface components of both C. gingivalis and F. nucleatum.
      Blocking studies showed that Fc gamma but not IgG inhibited IgM-RF binding to
      both micro-organisms. CONCLUSIONS: These findings indicate that the RF detected
      in the serum of some periodontitis patients may be elicited by certain micro
      organisms in the subgingival plaque. Furthermore, C. gingivalis and F. nucleatum
      appear to express surface antigen epitopes that are antigenically related to
      determinants on IgG can induce cross-reactive IgM-RF.

PMID- 9171509
TI  - Matrix metalloproteinases-1, -3 and -8 and myeloperoxidase in saliva of patients
      with human immunodeficiency virus infection.
AB  - OBJECTIVE: Human immunodeficiency virus (HIV)-seropositive patients have
      frequently severe gingival inflammation and/or attachment loss. In addition many
      infectious diseases affect their periodontium with varying clinical
      manifestations. Matrix metalloproteinases seem to play a key role in
      physiological periodontal remodelling and pathological tissue destruction. The
      aim of the present study was to characterize the presence, molecular forms,
      cellular sources, activities, and relative amounts of fibroblast-type (matrix
      metalloproteinase [MMP]-1) and neutrophil (MMP-8) collagenases, as well as their
      potential activator stromelysin-I (MMP-3) and myeloperoxidase in saliva of HIV
      seropositive patients at different phases of HIV-infection. HIV-seronegative,
      healthy, age-matched patients served as controls. PATIENTS AND METHODS: Saliva
      samples were characterized by Western blotting using antibodies specific for MMP
      1, MMP-3 and MMP-8. Interstitial collagenase activities were measured using
      quantitative sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis/laser densitometry assay. Myeloperoxidase was analysed using
      quantitative dot blotting. RESULTS: Clinical and microbiological evaluation of
      HIV-seropositive patients' periodontium showed the presence of putative
      periodontopathogens ie Actinobacillus actinomycetemcomitans (Aa), Porphyromonas
      gingivalis (Pg), Prevotella intermedia (Pi), Peptostreptococcus micros (Psm) and
      Campylobacter rectus (Cr) in their periodontal pockets. The amount of Candida
      increased with the severity of HIV-infection. Clinical and microbiological
      findings of HIV-seropositive patients suggested that they have a tendency to
      develop periodontal disease. Interstitial collagenase activities were found to be
      increased in saliva of different phases of HIV-infected patients compared to the
      controls. Independent of the phase of HIV-infection saliva samples contained pro-
      and active forms of MMP-1, -3 and -8 using Western blotting. Saliva samples from
      healthy controls were found to contain hardly any immunoreactivities for MMP-1 or
      MMP-8, but considerable amounts of MMP-3 were detected. Quantitative dot blotting
      demonstrated increased amounts of myeloperoxidase in HIV-patients' saliva
      relative to controls. CONCLUSION: The present results showed increased amounts of
      MMP-1, -3, -8 and myeloperoxidase in HIV-patients' saliva. MMP-1 and -8 may have
      been activated by MMP-3 and/or oxidants generated by myeloperoxidase. The
      increased amounts of MMPs and myeloperoxidase may reflect and directly
      participate in HIV-infection associated periodontitis.

PMID- 9171510
TI  - Hydrolytic and depolymerising enzyme activity of Prevotella intermedia and
      Prevotella nigrescens.
AB  - OBJECTIVE: Prevotella intermedia has been reported to be associated with
      periodontal disease whilst P. nigrescens has predominantly been isolated from
      more specific conditions and healthy sites. The aim of the present study was to
      compare the enzyme activity of these species. MATERIALS AND METHODS: Nine strains
      of P. intermedia and 12 strains of P. nigrescens were studied. Lipolytic,
      saccharolytic, nucleolytic and proteolytic activity was determined by traditional
      microbiological and chromogenic substrate methods. RESULTS: All strains
      hydrolysed gelatine, casein, DNA and RNA. Lipase activity was produced by all
      strains except P. nigrescens ATCC 33563T. Lipolytic activity of P. nigrescens
      strains decreased as the environmental glucose concentration was increased. Only
      two strains, both P. intermedia, hydrolysed benzyl-arg-rho-nitroanilide. All
      strains hydrolysed alkaline rho-nitrophenolphosphate (except P. intermedia
      DAL100), produced glycylprolyl dipeptidase activity and demonstrated elastase
      like activity. All but three strains (2 P. intermedia and I P. nigrescens)
      hydrolysed suc-ala-ala-pro-phe-rho-nitroanilide. Overall, no qualitatively
      analysed enzyme activity was exclusive to all strains of either species.
      Quantitatively analysed activity exhibited a high degree of variability both
      within and between species. CONCLUSIONS: P. intermedia and P. nigrescens degrade
      natural and synthetic substrates, but intra- and interspecies activity is
      variable.

PMID- 9171511
TI  - Apoptosis-associated proteins in oral hairy leukoplakia.
AB  - OBJECTIVE: To test the hypothesis that the anti-apoptotic ability of Epstein-Barr
      virus (EBV) may result in altered expression of apoptosis-associated proteins in
      oral hairy leukoplakia (HL), we evaluated HL tissue and normal epithelium for
      these proteins by immunohistochemistry. MATERIALS AND METHODS: Twenty formalin
      fixed, paraffin-embedded specimens of HL lesions and six specimens of normal
      control mucosa were selected from archived tissue specimens. Bcl-2, Bcl-x, Bax
      and p53 apoptosis-associated proteins were evaluated in immunohistochemically
      stained tissue sections according to staining intensity and pattern. The
      percentage of p53-positive basal cells was estimated in sequential fields.
      RESULTS: Generally, there were only slight differences in the expression of Bcl-2
      and Bcl-x proteins in the epithelium of HL and control tissue. The staining for
      Bcl-2 was weaker in keratinocytes than in putative melanocytes and Langerhans
      cells. Equivocal diffuse cytoplasmic staining of prickle cells was also noted.
      Keratinocytes throughout the epithelium stained positively for Bcl-x protein,
      although upper layers were more weakly stained. The 'balloon' keratinocytes in HL
      were infrequently positive for Bcl-x. Bax staining in HL differed from that in
      control tissue in being more heterogeneous. The staining reaction in HL was weak
      to negative in upper epithelial levels where 'balloon' keratinocytes were
      located. Weak to moderate nuclear p53 protein staining was detected in a mean of
      25.3% of basal keratinocytes in all but one of the HL specimens; weak staining
      was seen in only two control specimens. CONCLUSIONS: We found only slight
      immunohistochemical evidence that expression of the apoptosis-associated proteins
      is altered in HL. p53 appears to over-expressed in HL; we speculate that this may
      be related to up-regulation or stabilization of wild-type p53 protein related to
      EBV infection.

PMID- 9171512
TI  - Oral candidosis in long-term hospital care: comparison of edentulous and dentate
      subjects.
AB  - OBJECTIVE: To obtain information on the oral health status of the elderly living
      in a medicalized, geriatric institution. DESIGN: A cross-sectional clinical
      investigation with complementary microbiological studies. SUBJECTS AND METHODS: A
      cohort of 233 elderly in one long-term care ward; collection of demographic data;
      clinical examination to determine dental and prosthetic status and health of the
      oral mucosae; swabs for detection of mucosal and denture colonization by Candida;
      paraffin stimulated saliva for detection of colonization by mutans streptococci
      and lactobacilli. MAIN OUTCOME MEASURES: Oral and denture hygiene; oral mucosal
      health; degree of colonization by Candida, mutans streptococci and lactobacilli.
      RESULTS: Mean age of the 233 patients was 85.6 +/- 6.9 years; 61% were totally
      dependent, 62.7% were wearing one or two complete dentures; 19.7% had natural
      teeth and no denture and 17.6% neither teeth nor denture. Of those wearing
      dentures 72% had denture stomatitis. Of those with natural teeth 72% were
      affected by active caries. Yeast counts were significantly correlated with the
      intensity of the erythema of the palatal mucosa, plaque score of the natural
      teeth, denture plaque score, and salivary counts of mutans streptococci and
      lactobacilli. CONCLUSIONS: High oral yeast counts and frequent prevalence of oral
      candidosis in elderly subjects living in institutions are associated with poor
      oral hygiene and neglect of denture care.

PMID- 9171513
TI  - Prevalence of oral leukoplakia in 1000 Berliners.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of oral
      leukoplakia and other oral white lesions in an urban population of non-referred
      patients to a department of oral surgery in the city of Berlin. DESIGN: A total
      of 1000 patients over the age of 16 were evaluated for oral leukoplakia and other
      oral white lesions. Age, sex, and smoking as well as alcohol habits were
      recorded. RESULTS: Of 506 men (50.6%) and 494 women (49.4%), 0.9% showed oral
      leukoplakia. Men were more frequently affected (1.6%) than women (0.2%). Patients
      of older age groups were more frequently affected than younger patients. Other
      white oral lesions were recorded such as leukoedema (8.3%), smoker's palate
      (0.1%), frictional white lesions (2.6%) and lichen planus (0.6%) with equal
      distribution between men and women. CONCLUSION: The prevalence of oral
      leukoplakia in this limited group of urban patients was low, however comparable
      to that of other neighbouring west European countries. Association with tobacco
      and alcohol consumption was demonstrated as in most other studies.

PMID- 9171514
TI  - TCR V beta gene expression in lesional T lymphocyte cell lines in oral lichen
      planus.
AB  - To study V beta gene expression in oral lichen planus (OLP) lesional T
      lymphocytes cell lines. MATERIALS AND METHODS: Lesional T lymphocytes were
      isolated from eight OLP patients and cell lines established. The total RNA was
      extracted from these lymphocyte cell lines and reverse transcribed. cDNA was
      amplified by the polymerase chain reaction (PCR) using a panel of 26 V beta
      specific oligonucleotide primers followed by qualitative analysis of the
      electrophoresed reaction products. RESULTS: V beta 1, 2, 3, 5.1, 6.1-3, 7, 8, 9,
      22, 23, and 24 were represented consistently in all of the OLP samples, V beta
      11, 12, and 17 were consistently negative, while the other V beta families (V
      beta 4, 5.2-3, 10, 13.1, 13.2, 14, 15, 16, 18, 19, 20, and 21) were variable. V
      beta 22 and 23 were the most strongly expressed in all patients. CONCLUSIONS: A
      limited T cell receptor (TCR) gene usage indicates a degree of oligoclonality
      within these lesional T lymphocyte cell lines from OLP. This implies that OLP may
      be an antigen-specific disease or linked to a limited number of superantigens.

PMID- 9171515
TI  - Pigmented lateral periodontal cyst and other pigmented odontogenic lesions.
AB  - OBJECTIVE: To report a case of lateral periodontal cyst (LPC) with marked melanin
      pigmentation in a 38-year-old Black male and to discuss the phenomenon of melanin
      pigmentation in odontogenic cysts and tumors. RESULTS: Histologically, the
      epithelial lining of the LPC contained an abundant amount of melanin granules
      throughout the entire epithelium. Ultrastructurally, epithelial cells contained
      mature melanosomes (stage IV melanosomes). Melanophages containing aggregates of
      melanosomes were identified in the connective tissue cyst wall. Perusal of the
      literature revealed that melanin pigmentation in odontogenic lesions is uncommon.
      Melanin has been reported in calcifying odontogenic cyst (18 cases), odontogenic
      keratocyst (8 cases), adenomatoid odontogenic tumor (3 cases), ameloblastic
      fibroma (3 cases), odontoma (2 cases), and ameloblastic fibro-odontoma, odonto
      ameloblastoma, and odontogenic fibroma (1 case each). CONCLUSIONS: Almost all
      pigmented odontogenic lesions; occurred in Blacks and Asians; they are almost non
      existent in Whites. Thus, racial pigmentation probably plays an important role in
      such lesions.

PMID- 9171516
TI  - Oral mucosal lesion associated with sickle cell disease.

PMID- 9171517
TI  - Cerebral resuscitation after global brain ischemia: linking research to practice.
AB  - Despite significant advances in resuscitation medicine, neurologic recovery
      continues to be the major limiting factor in achieving successful resuscitation
      outcomes. Clinicians must recognize that successful resuscitation outcomes are
      not limited to the restoration of normal cardiac rhythm and hemodynamics, but
      rather the restoration of human mentation. It is well recognized that a cascade
      of injurious events begins within minutes of ischemia and that ischemic and
      postischemic events cause significant neuronal damage. An increased understanding
      of the pathophysiology of global brain ischemia provides evidence of a
      therapeutic window of opportunity during which interventions hold the potential
      to improve neurologic outcome. The research basis for understanding global brain
      ischemia, its clinical prognosis, and potential intervention strategies are
      examined.

PMID- 9171518
TI  - The complexity of caring for patients with ruptured cerebral aneurysm: case
      studies.
AB  - Ruptured intracerebral aneurysm causes instantaneous neurologic chaos and is
      associated with high morbidity ad mortality. The event initiates a cascade of
      physiologic and structural changes that manifest themselves in a variety of
      clinical symptoms. The critical care team of nurses, physicians, and therapists
      must rapidly identify the cause; understand the pathology; and use advanced
      assessment techniques, medications, and interventions to stabilize the patient
      and to counter the horrendous effects of the injury. Interventions that include
      endovascular aneurysm coiling and cerebral angioplasty are providing new options
      for isolating the aneurysm and countering the effects of vasospasm. Through an
      integrated team approach, recovery from ruptured aneurysm will be maximized.

PMID- 9171519
TI  - Giant intracranial aneurysm obliteration using deep hypothermic circulatory
      arrest.
AB  - Giant intracranial aneurysms pose significant technical problems for the
      neurosurgical team. Because of the location and structure of these lesions, the
      risks associated with traditional surgical techniques are usually unacceptable.
      Although aneurysm clipping using deep hypothermic circulatory arrest was first
      described 30 years ago, it was nearly abandoned because of poor outcomes
      associated with the systemic and cardiac complications of extracorporeal
      circulation. Advances in cardiopulmonary bypass techniques have inspired renewed
      interest in the use of this method in surgery for intracranial aneurysm. Deep
      hypothermic circulatory arrest, using low-flow states, has yielded exceptional
      patient outcomes. This increasingly popular means of management provides unique
      challenges to the neurosurgical health care team. Understanding the pre-, intra-,
      and postoperative care of these patients is imperative for neurosurgical nurses
      of the twenty-first century.

PMID- 9171520
TI  - New developments in managing transient ischemic attack and acute stroke.
AB  - During this decade, which has been designated the decade of the brain, the event
      of transient ischemic attack (TIA) or acute ischemic stroke is considered a brain
      attack requiring rapid diagnosis and treatment. This increased focus on the
      clinical problems of TIA and stroke has resulted in rapid advances in management
      of this patient population. This article will highlight for critical care nurses
      some of the many advances in patient management of TIA and stroke that have
      occurred in the past few years. Advances in the areas of diagnostic studies,
      pharmacologic interventions, and nursing care will be covered. Furthermore, some
      of the new developments on the horizon will be summarized.

PMID- 9171521
TI  - Posterior fossa tumors in children: a case study.
AB  - Brain tumors are the second most common malignancy to occur during childhood and
      the posterior fossa is the most common region of the brain affected. Diagnosis
      and treatment are complex and challenging. Once a child suffering from a
      posterior fossa tumor is identified, a multidisciplinary team must be assembled
      to provide comprehensive care through all phases of treatment. The nursing staff
      is vital to this team because they are often the individuals who coordinate
      services involved in the care of the child with a posterior fossa tumor. This
      case study illustrates the phases of diagnosis and treatment of a child with a
      medulloblastoma and highlights critical care nursing challenges. Following the
      case study presentation, a summary describes posterior fossa tumors including
      epidemiology, pathophysiology, clinical manifestations, and outcome. The case
      study is integrated throughout this review to highlight key issues for critical
      care nurses to explore.

PMID- 9171522
TI  - Advanced practice and neuroscience nursing.
AB  - In this report Calkin's model of advanced practice is used to contrast
      generalized/specialized and basic/advanced nursing practices. Examples of
      specialized and advanced practices in neuroscience nursing are described in the
      context of environmental forces that influence advanced practice in North
      America. Finally, a letter from the future is used to speculate and to illustrate
      visions of nursing practice in the twenty-first century.

PMID- 9171523
TI  - CORE characteristics for survival in patient care redesign.
AB  - As patient care delivery systems evolve and facility redesign occurs, innovative
      models of care delivery require clinicians to possess certain qualities for
      successful implementation of redesign efforts. Certain specific "CORE" abilities
      are key for all clinicians. They are: C: the ability to think critically,
      communicate, and collaborate with patients, families, and other health care team
      members. O: the need to be outcome-oriented, that is, striving to optimize
      patient and family outcomes along the continuum. R: realization of the value of
      research and the ability to use research resources to develop and evidence-based
      practice. E: the ability to keep abreast of a wide variety of clinical and other
      health care-related topics. Demonstration of these CORE abilities will increase a
      clinician's opportunity to achieve professional success into the 21st century.

PMID- 9171524
TI  - Strategies to integrate patient and family education into patient care redesign.
AB  - This article discusses five strategies to effectively integrate patient and
      family education into patient care redesign. The strategies include building the
      plan, building a shared mission and vision, building involvement, building
      collaboration through initiatives, and building accountability. Each strategy or
      "building block" is vital to the resulting structure of patient and family
      education. Effective results of the strategies are discussed as milestones. The
      process must be ongoing to ensure continuous improvement in quality patient care
      outcomes, consumer satisfaction and cost-effectiveness.

PMID- 9171525
TI  - Re-engineering intensive care: the role of informatics.
AB  - Managed care and quality improvement are two driving forces in the current health
      care environment. The pressure of capitation and the recent focus on outcomes of
      care have generated new incentives to restructure care delivery to control costs.
      Intensive care units, once revenue centers, are becoming cost centers. Re
      engineering, or redesigning, the process of care entails examining premises for
      ability to provide services as well as considering how to do things more
      efficiently. The assumption is that all aspects of a process are legitimately
      subject to examination and restructuring. Information systems provide a powerful
      tool to support re-engineering. Nursing informatics, which pertains to nursing
      data, information, and knowledge has major implications for hospital information
      systems. This article explores possible changes in intensive care and the role of
      informatics in a changing health care environment.

PMID- 9171526
TI  - The advanced practice nurse's role in differentiated practice: Martha's story.
AB  - The changing health care environment and increasing patient acuity necessitate a
      coordinated effort among all health care disciplines to assure the best patient
      outcomes. The advanced practice nurse in the role of case manager is well
      qualified to serve as the leader of this team. Within the framework of
      differentiated practice, advanced practice nurses work in tandem with associate
      and primary nurses to ensure positive quality, financial, and satisfaction
      outcomes. Clinical expertise and knowledge of systems allow the advanced practice
      nurse to assist the patient through complex systems to achieve these ends.

PMID- 9171527
TI  - Holistic acute care units: partnerships to meet the needs of the chronically ill
      and their families.
AB  - The traditional acute care health care environment does not meet the needs of
      chronically ill patients and their families. The classic paternalistic approach
      encourages dependence on the health care team. This report reviews several
      innovative types of patient care delivery models, including patient-focused care,
      family-centered care, cooperative care, and Program Planetree. The core concepts
      of these various models are described and compared. Related research is
      presented. A synthesis of these existing models to meet the needs of chronically
      ill medical patients holistically is proposed. The implementation of the holistic
      model with chronically ill patients and their families is depicted.

PMID- 9171528
TI  - Credentialing. Concerns and issues affecting occupational health nursing.
AB  - 1. Mechanisms for credentialing affecting occupational health nursing include
      licensure and certification of individuals and accreditation of educational and
      health care organizations. 2. Issues of control of entry into practice,
      geographic mobility, and whether licensure will be single or two tiered, national
      or institutional, are currently under debate. 3. The purpose of certification is
      to acknowledge the individual and assure the public that the individual has
      mastered a body of knowledge of a particular specialty. 4. The purpose of
      accreditation is to evaluate the performance of a service (i.e., education or
      health care) and to provide consumers of that service necessary information on
      which to base decisions on use of the services. 5. Occupational health nurses
      must participate actively in the process of credentialing clarification and
      reform to be prepared to advance the specialty and respond to the health care
      needs of the working population in the 21st century.

PMID- 9171529
TI  - Facilitating behavior change. Use of the transtheoretical model in the
      occupational health setting.
AB  - 1. Researchers have identified five stages of change and the 10 experiential and
      behavioral processes most effective in helping people move from one stage to the
      next. This model is referred to as "transtheoretical" because it encompasses many
      theories of behavior change. 2. Each stage of change tends to be characterized by
      the use of specific processes. Experiential strategies are used most frequently
      by individuals in the contemplation and preparation stages of change. Behavioral
      processes are used most frequently by individuals in the action and maintenance
      stages. 3. The transtheoretical model assists providers in developing
      interventions targeted not only for employees who are prepared to take action,
      but also for the majority of the population who are not yet intending to change
      their behavior, or for those who are only considering a lifestyle change. 4.
      Using this information, the occupational health nurse can design specific
      interventions targeted to an individual's current stage of change, with the
      potential to accelerate the employee's progress toward increasing the adoption
      and maintenance of the desired behavior.

PMID- 9171530
TI  - Implementing a self care program. Effect on employee health care utilization.
AB  - 1. One way to reduce health care costs is to reduce the demand for health care
      services. This can be accomplished by teaching employees to make better decisions
      about when they should see the health care provider or go to the emergency
      department versus treating themselves at home using self care. 2. In an effort to
      reduce health care costs, a manufacturing company implemented a self care program
      using a publication called the HealthyLife Self Care Guide. The guide was
      distributed to employees during a 50 minute workshop. 3. Analysis of claims data
      1 year prior to distribution of the Guide and 1 year after distribution showed a
      savings of $39.65 per employee (a 24.4% decrease in costs) due to reduced health
      care provider and emergency department visits. This amounted to a return on
      investment of 2.6:1. 4. It appears that implementing a self care program in a
      worksite setting can be an effective way to reduce employer health care costs.

PMID- 9171531
TI  - Health beliefs of blue collar workers. Increasing self efficacy and removing
      barriers.
AB  - The study compared the health beliefs of participants and non-participants in a
      blood pressure and cholesterol screening held at the worksite. A cross sectional,
      ex-post facto design was used. Questionnaires measuring health beliefs related to
      cardiac screening and prevention of cardiac problems were distributed to a
      convenience sample of 200 blue-collar workers in a large manufacturing plant in
      the Midwest. One hundred fifty-one (75.5%) completed questionnaires were
      returned, of which 45 had participated in cardiac worksite screening in the past
      month. A multivariate analysis of variance was used to analyze data. Participants
      perceived significantly fewer barriers to cardiac screening and scored
      significantly higher on self efficacy than non-participants. These findings
      concur with other studies identifying barriers and self efficacy as important
      predictors of health behavior. Occupational health nurses' efforts are warranted
      to reduce barriers and improve self efficacy by advertising screenings,
      scheduling them at convenient times and locations, assuring privacy, and keeping
      time inconvenience to a minimum.

PMID- 9171532
TI  - Aging issues in the workplace. Assisting workers who provide eldercare.
AB  - 1. With increased aged, chronic disabilities that limit the ability to provide
      self care also increase. As self care declines, elderly persons depend on their
      children for assistance. 2. Families provide 80% of home based care for the
      elderly. Employees' children often provide care. 3. Caregiving has both positive
      and negative aspects. Caregiving often leads to psychological stress and, over
      time, physical illness for the caregiver. 4. Occupational health nurses can
      assist employee caregivers in protecting their own health and locating services
      for their care recipients.

PMID- 9171533
TI  - Business skills for occupational health nurses: the interview.

PMID- 9171536
TI  - Assessment of the patient with chest pain in the accident and emergency
      department.
AB  - This article will review measures enabling emergency staff to identify patients
      with chest pain who are likely to need admission to a cardiac care unit, in
      particular those with manifestations of acute ischaemic heart disease--acute
      myocardial infarction and unstable angina. Other non-cardiac causes of chest pain
      will also be discussed.

PMID- 9171535
TI  - Surgical staple trial in accident and emergency.
AB  - A trial was undertaken at the John Radcliffe Hospital, Oxford to establish if
      surgical staples were a viable alternative to traditional sutures in wound
      closure. The trial involved a sample of trained nursing staff using staples in
      the closure of simple skin lacerations presented at the Accident and Emergency (A
      & E) department. A questionnaire collected subjective and objective information
      from staff and patients relating to insertion and removal of the staples.
      Although there was no comparative data available for sutured wounds, the results
      indicated that staff were satisfied with the stapler's ease and speed of use. It
      was concluded that stapling was a viable addition to the choice of skin closure
      technique, rather than an alternative.

PMID- 9171534
TI  - Do nurses need an identity?

PMID- 9171537
TI  - Innovation in accident and emergency management: establishing a nurse
      practitioner-run minor injuries/primary care unit.
AB  - The establishment of a nurse practitioner-run Minor Injuries and Primary Care
      Unit in the Accident and Emergency department of an east London district general
      hospital is outlined. The establishment of clinical protocols, operational
      policies, staff recruitment and training, budgeting and publicity are discussed.
      The effective utilization of emergency nurses' skills is illustrated by a
      reduction in waiting times, standardized optimum clinical practice, improved
      patient satisfaction, increased health promotion opportunities and improved
      communication and referrals to, and from, Primary Care facilities. The potential
      for other such units and the changing role of A & E departments is highlighted.

PMID- 9171538
TI  - Protecting children in the accident and emergency department.
AB  - Approximately one-third of patients attending Accident and Emergency departments
      are children and their differing needs are currently on the health care agenda.
      Nurses working in A & E will treat and care for children for whom a possibility
      of abuse or neglect may be raised. This article explores the concept of child
      protection and discusses the role of the nurse in relation to UK Government
      guidelines and legislation. These, in turn, inform local procedures and
      guidelines for practice. While the work of A & E departments is often crucial,
      most child protection work should take place in community child health settings.

PMID- 9171539
TI  - The work of accident and emergency nurses: Part 2. A & E maxims: making A & E
      work unique and special.
AB  - An ethnomethodological study was undertaken to explore the work of Accident and
      Emergency (A & E) nurses; the aim of which was to analyse the ordinary, taken for
      granted, everyday work of those practising A & E nursing. In this second paper on
      the work of A & E nurses, the specific rules or maxims of nursing work in A & E
      are introduced. From the analysis of materials gained: fieldwork notes,
      observations of nurses at work and conversations, a number of maxims of A & E
      nursing work were identified. Maxims direct, instruct and make nurses accountable
      for their work and the ways in which it gets done. That is, the presence of
      maxims underpinning A & E nursing work ensure that A & E nursing is seen and
      heard as a specific type of work with its own unique approach to talk and
      organization. Being aware of the maxims of A & E nursing work is not the concern
      of the nurse practising A & E nursing on a daily basis. Implicit and explicit
      reference to the maxims when talking about and doing the work provides nurses
      with impressions of who can do the job. Non-adherence by some nurses to the
      maxims of A & E nursing work often leads their colleagues to question their
      commitment to their choice of work setting. Maxims of A & E nursing account for
      the ways in which the work is seen, heard and talked about. Maxims direct the
      organization of work and its development within the A & E setting.

PMID- 9171540
TI  - Children in accident and emergency.
AB  - The purpose of this paper is to examine the many issues surrounding the care of
      children within Accident and Emergency (A & E) departments. A review of relevant
      literature reveals the principles that are pertinent to the care of the child in
      hospital and specifically within an A & E department. Theories of child
      development are introduced and discussed in relation to nursing care of children.
      The reflective cycle is used to examine two critical incidents. The analysis of
      these events allows further scrutiny of the ideas relating to the care of
      children and illustrates the way in which such ideals can be used to guide
      practice. The authors concludes that a sound knowledge of the developmental
      process of the child, and an understanding of the particular issues relevant to
      the care of the child within the accident and emergency environment can ensure
      optimum care for each child and their family.

PMID- 9171541
TI  - Evidence-based suction management in accident and emergency: a vital component of
      airway care.
AB  - Effective airway management aims to establish and maintain a patent airway to
      ensure adequate alveolar ventilation and patient survival. Suction therapy must
      be regarded as a vital component of airway care, with all staff who are required
      to perform this procedure being aware of the principles of safe, effective
      suctioning. This paper provides an outline of the types of suction catheters
      available for use in the emergency care setting, and describes the safe
      procedures to be followed for both endotracheal and oro-pharyngeal suctioning.
      Potential complications are discussed other headings of respiratory,
      cardiovascular, immunological and traumatic, all of which are relevant to safe
      patient care whatever the setting, and all of which should be recognizable by any
      staff undertaking this procedure. The final section looks at the ways in which
      some of the complications can be minimized or detected by relating some of the
      more important theoretical points discussed throughout the paper to the practical
      situation. Suction therapy is not without risk for the patient and, although the
      frequency of suction therapy is far less in Accident and Emergency (A & E) than
      in the Intensive Care Unit, the potential dangers remain the same. In order to
      minimize some of the dangers and reduce confusion amongst staff, this paper
      concludes with a recommendation for a degree of standardization in suction
      catheter use.

PMID- 9171542
TI  - Creating the casualty: role of casualty simulation in accident and emergency
      training.

PMID- 9171543
TI  - Inappropriate attendance in accident and emergency.
AB  - Patients who attend Accident and Emergency (A & E) departments with problems that
      could be dealt with by their general practitioners (GPs) use time and resources
      of the department that could be otherwise used for patients with more appropriate
      needs. Definitions used for inappropriate attendance are drawn from the
      literature, and the usefulness of the term is discussed in the light of evidence
      that these patients have logical reasons for attending. Methods of improving the
      service offered to these patients are discussed, including emergency nurse
      practitioners, minor injuries units and GPs in the A & E department. The
      reluctance of GPs to treat minor injuries in their surgeries is noted. The
      implications of changing the service provided in A & E to accommodate or deter
      patients with primary care problems are discussed.

PMID- 9171544
TI  - Cardiac arrest: the skills of the emergency nurse practitioner.
AB  - This paper seeks to explore the skills that the Emergency Nurse Practitioner
      (ENP) should have in relation to cardiopulmonary resuscitation (CPR). No specific
      literature was found relating to the role of the ENP in CPR. Therefore, three
      literature searches were carried out and the findings used to suggest skills in
      which the ENP should be competent. As demand for community based minor injuries
      units (MIUs) grows, development of an independent role for ENPs should reflect
      their unique relationship with patients. These patients may have illnesses in
      addition to the injuries with which they present. If a patient collapses in
      cardiac arrest, the prompt and correct response of the ENP would be the most
      important factor in increasing the patient's survival chances (European
      Resuscitation Council 1992a & b, Handley & Swain 1994). The majority of sudden
      cardiac arrests are caused by ventricular fibrillation (VF) (Royal College of
      Physicians 1987). Therefore, competence in defibrillation is one area of nursing
      role expansion which should be adopted by an ENP during the role transition. This
      should be supported by biannual training in Basic Life Support (BLS) to ensure
      that ENPs are able to manage cardiac arrests effectively. Nationally recognized
      training is recommended in order to facilitate ENP movement between Trusts.

PMID- 9171545
TI  - The will.

PMID- 9171546
TI  - Sorted.
AB  - Each year in Accident and Emergency an increasing number of young people present
      with acute problems related to social drugs. These problems range from mild
      symptoms to life-threatening conditions, many of which can be extremely difficult
      and time consuming for staff to manage. It has become apparent that as with sex
      the experimental age for taking drugs is getting younger as youths are now far
      more 'streetwise' than their predecessors. This is one of the main reasons for
      this paper being written; it is imperative that staff are equipped with the
      appropriate knowledge to deal with the challenge and are educated about the
      problems associated with current drug trends. This potentially improves the
      quality of care and, in turn, good communication improves relationships. Ecstasy
      is once again becoming increasingly popular within mainstream clubs, as recently
      highlighted in the media, and with it reappear its problems. This article
      discusses the historical aspects of Ecstasy and aims to educate staff about its
      use and effects and provides health promotion advice for those who are involved
      in the care of people who take Ecstasy.

PMID- 9171547
TI  - Holiday traumas.

PMID- 9171548
TI  - The decision to seek death. Is it free and informed?

PMID- 9171549
TI  - Coordinating care in the rural setting.

PMID- 9171550
TI  - Terminally ill cancer patients. Their most important concerns.
AB  - PURPOSE: When the goal of treatment is palliative, the most important outcome is
      improving patient quality of life. The authors describe the major concerns of
      terminally ill cancer patients with a prognosis of 6 months of less. OVERVIEW: In
      phase I of this three-part study, 74 terminally ill patients were interviewed to
      identify their major concerns. In phase II, interviews with 120 terminally ill
      cancer patients showed that their most important concerns encompass existential,
      spiritual, familial, physical, and emotional issues. Phase III will determine the
      validity and reliability of a quality-of-life scale based on these patients' most
      important concerns. The information presented here summarizes the results of
      interviews from phases I and II. CLINICAL IMPLICATIONS: Patients were receptive
      to being interviewed and remarked on the relevance and importance of these issues
      to their own experience. Several patients commented that although their disease
      was assessed and reassessed throughout their care, the existential, spiritual,
      familial, and emotional aspects of their illness rarely were a focus of their
      care. Healthcare professionals can create an atmosphere in which these patients
      feel comfortable exploring the quality-of-life issues that are most important to
      them. The systematic assessment of patient concerns about quality of life may
      complement disease assessment and facilitate referrals to appropriate members of
      the healthcare team. The wide range of concerns reported suggests that a team
      approach, including physicians, nurses, social workers, psychiatrists,
      psychologists, and chaplains, is the most effective way to meet the needs of
      terminally ill patients.

PMID- 9171551
TI  - Enforced social dependency and its relationship to cancer survival.
AB  - PURPOSE: This study examined relationships between survival time and enforced
      dependency in a group of patients with cancer. DESCRIPTION OF STUDY: Data are
      reported from 141 patients with solid tumor cancers who participated in an
      interview around the time of their discharge from the hospital. Measures included
      medical history, demographic characteristics, and five measures of psychosocial
      status, including enforced personal and social dependency. Patients were followed
      2 to 4 years later to ascertain survival status and, for those who had died,
      dates of death. Psychosocial variables were used as potential predictors in a
      multivariate model of survival time, which also included variables measuring
      severity of illness. RESULTS: Enforced personal and social dependency, but not
      the other psychosocial variables, were found to contribute significantly to the
      model of survival time. CLINICAL IMPLICATIONS: These findings suggest that
      survival of patients with cancer might be improved by an intervention targeted at
      enforced social dependency.

PMID- 9171552
TI  - Patient satisfaction with an informed consent process.
AB  - PURPOSE: This study evaluates patient and family member level of satisfaction
      with alternative approaches in obtaining informed consent before colonoscopy or
      upper gastrointestinal endoscopy. DESCRIPTION: A convenience sample of 204
      endoscopy patients at Memorial Sloan-Kettering cancer Center in new York and 102
      of their family members were approached to participate in the study. All patients
      were 19 years of age or older, able to speak and read English, and mentally
      competent. After proceeding through the informed consent process using both
      videotape and physician discussion, participants completed a ten-question survey
      on their previous informed consent experience and their preferences regarding
      receiving consent information. RESULTS: Overall, participants reported that a
      combination of videotape and physician explanation was preferred for receiving
      consent information over either method alone. The participants found that the
      videotape helped to make the information easier to understand and provided the
      appropriate amount of information about risks, benefits, and alternatives to the
      prospective endoscopic procedure. CLINICAL IMPLICATIONS: Patient satisfaction
      should be a factor in determining the best method of providing informed consent
      information. Because this study indicates that participants are most satisfied
      with the method of videotape followed by physician discussion, the addition of
      the videotape to the informed consent process may be beneficial in preparing the
      participant for a meaningful dialogue with the physician. The use of the
      videotape also may eliminate the problem of readability of the written document
      and ensure that all patients receive the same information. With a concerted
      effort on the part of oncology healthcare providers, including oncologists,
      nurses, and patient education professionals, this method may hold promise for
      ensuring the achievement of informed consent in oncology patients.

PMID- 9171554
TI  - Mechanisms and management of amphotericin B-induced nephrotoxicity.
AB  - PURPOSE: The author outlines the care of patients receiving intravenous
      amphotericin B, with emphasis on the prevention and/or management of
      nephrotoxicity. OVERVIEW: The immunocompromised patient remains at risk for
      systemic fungal infections; however, therapeutic options are limited. Although
      amphotericin B has remained the drug of choice for more than 30 years, its toxic
      effects, particularly nephrotoxicity, warrant careful attention. Nephrotoxicity
      is the most serious and dose-limiting effect of amphotericin B therapy.
      Appropriate assessment before, during, and after therapy in patients receiving
      intravenous amphotericin B may help to minimize the potential for nephrotoxicity.
      CLINICAL IMPLICATIONS: To provide optimal patient care, it is imperative that the
      clinician understand the etiology of and the signs and symptoms associated with
      nephrotoxicity, as well as interventions to prevent nephrotoxicity, in the
      patient receiving amphotericin B.

PMID- 9171553
TI  - Computerized quality-of-life screening in an oncology clinic.
AB  - PURPOSE: The purpose of these studies was to assess the feasibility and
      reliability of computerized quality-of-life screening for patients attending an
      outpatient breast cancer clinic. The screening program involved a computerized
      administration of the European Organization for Research and Treatment of cancer
      QUality of Life Questionnaire (EORTC QLQ-C30). The computer software generated a
      screening report that clinic staff members used in the clinical encounter to
      assist in identifying quality-of-life problems. DESCRIPTION OF STUDY: Two studies
      are reported. In study I, 36 patients and either their nurses or physicians
      evaluated the feasibility of the screening program using questionnaires developed
      for this study. In study II, a separate sample of 50 patients completed both the
      computerized and paper-and-pencil versions of the QLQ-C30 to assess reliability
      and consistency of responding. RESULTS: The results of study I indicate that the
      patients found the computerized administration to be an acceptable means of
      providing staff members with information on day-to-day functioning. Clinic nurses
      and physicians indicated that the report was useful in identifying problematic
      quality-of-life domains. The results of study II indicate that the computerized
      administration is highly correlated with the paper-and-pencil version and has
      similar internal consistency. Discrepancies in responses were identified, but
      were at an acceptable level. CLINICAL IMPLICATIONS: The results of these studies
      indicate that computerized quality-of-life screening is feasible and may provide
      reliable data for research and quality assurance studies. Staff evaluations
      suggest that the written report may provide clinic staff members with a tool for
      identifying quality-of-life concerns in which individual patients are
      experiencing difficulty. Potential benefit to patients include productive use of
      waiting room time, greater efficiency in the assessment process, and an improved
      likelihood that nurses and physicians will recognize and attend to quality-of
      life deficits. The valid, reliable, and efficient identification of important
      patient quality-of-life concerns allows multidisciplinary team members to focus
      meaningfully their clinical efforts within their respective areas of
      responsibility.

PMID- 9171555
TI  - Physician-assisted suicide. A private, professional, and public challenge.

PMID- 9171556
TI  - Advance directives for patients with cancer.

PMID- 9171557
TI  - Amifostine. A novel cytoprotective agent.

PMID- 9171558
TI  - Management of hemangiomas.
AB  - A majority of hemangiomas are harmless lesions and they regress spontaneously
      without significant sequelae. However, there are also distressing, endangering,
      and even life-threatening hemangiomas. For them, the outcome has improved over
      the last 10 years, and mortality figures have dropped due to promptness in
      treatment and to more effective therapeutic regimens. Parents need frequent
      consultations and support even when we decide not to treat the child, and
      pictures should be taken to follow the progress of involution.

PMID- 9171559
TI  - Cutaneous laser resurfacing: a nursing guide.
AB  - Cutaneous laser resurfacing has become a popular method to treat rhytides,
      atrophic scars, and a variety of epidermal and dermal lesions. While excellent
      results have been observed with this technology, complications have resulted when
      proper intraoperative and postoperative protocols are not followed. The nurse's
      role in proper patient education, preparation, and postoperative management is
      critical to the ultimate success of the procedure.

PMID- 9171560
TI  - Pressure ulcers: a public health problem, an integrated hospital's solution.
AB  - Pressure ulcers are an example of chronic medical problem that has a larger
      public health impact on our health care resources. An integrated health care
      delivery system is needed to attack the problem. A theoretical model recently put
      into place to address this issue is described.

PMID- 9171561
TI  - What's your assessment? Actinic (solar) lentigines.

PMID- 9171562
TI  - Diapers and diaper rashes.
AB  - The diaper-wearing population has expanded from infants and children to include
      adults, especially the elderly. Nurses caring for patients over a wide age range
      are commonly asked for advice about diapering choices, and for guidance in
      evaluation, prophylaxis, and treatment of diaper rashes. Two different diaper
      types, disposables and reusables, and the advantages and disadvantages of each
      are discussed. A systematic approach is presented for the nursing evaluation of
      common diaper rashes and their differentiation from rarer skin eruptions of the
      groin and perineum in diaper-wearing persons.

PMID- 9171563
TI  - Smoking cessation: information for specialists. AHCPR.
AB  - This Quick Reference Guide for Smoking Cessation Specialists contains strategies
      and recommendation from Smoking Cessation Clinical Practice Guideline No. 18,
      designed to assist clinicians, smoking cessation specialists, and health care
      administrators/insurers/purchasers into identifying tobacco users and supporting
      and delivering effective smoking cessation interventions. These recommendations
      were made as a result of an exhaustive and systematic review and analysis of the
      scientific literature.

PMID- 9171564
TI  - Occurrence of skin lesions/conditions in ill persons.
AB  - The purpose of this study was to examine the occurrence of common skin lesions
      that potentially may be misdiagnosed as a pressure ulcer, and to examine the
      characteristics of ill persons who have these skin changes. This was a
      prospective, descriptive study which included five acute care hospitals, a
      rehabilitation hospital, and a home care agency. Results indicated that patients
      with skin lesions/conditions were significantly older and had longer lengths of
      stay, more diseases, lower Braden Scale scores, and lower serum albumin levels.
      Nurses must gain knowledge about identifying and treating skin conditions.
      Assessment of the patient's skin should occur throughout their length of stay.

PMID- 9171566
TI  - What's your assessment? Tinea pedis.

PMID- 9171565
TI  - Chemical peel as a treatment for skin damage from excessive sun exposure.
AB  - The increased incidence of melanomas and other skin cancers has caused awareness
      of various other skin diseases resulting from too much sun exposure. People are
      more conscious of the appearance of their skin and skin aging, and are interested
      in treatment. Chemical peel is one of the most popular forms of therapy for
      certain skin disorders.

PMID- 9171567
TI  - Pressure ulcer prevention--the UK perspective.
AB  - Pressure ulcers are a universal problem. Much attention has been given to them in
      the United Kingdom in recent years. They are seen as a key indicator of the
      quality of care. Their prevention has become politically, as well as clinically,
      important.

PMID- 9171568
TI  - Common patch test allergens: general guidelines for avoidance.
AB  - Contact dermatitis is a very common diagnosis in the dermatology clinic.
      Simplified information offers a good starting point for patient education and
      instruction about avoidance measures. Using the general guidelines proposed here
      can be useful for the most common allergens, and will help motivate both the
      patient and providers to be active participants in solving the puzzle of allergic
      contact dermatitis.

PMID- 9171569
TI  - A reply to Kevin Gournay's 'Schizophrenia: a review of the contemporary
      literature and implications for mental health nursing theory, practice and
      education'.
AB  - Mental health nurses are being increasingly encouraged to move to a more
      biologically oriented approach. Authors such as Professor Gournay promulgate the
      myth that biological psychiatry will soon be able to provide an unambiguous model
      of the nature of mental disorder. A closer examination of some of the biological
      research identified by Gournay as moving us closer to this ideal reveals,
      however, the confused and unconvincing nature of the results so far achieved. In
      the light of this it seems premature to be advocating wholesale acceptance of the
      biological model by nursing. Nurses should be made aware of the investigations of
      the biologists, but, unless they are equipped with the necessary intellectual
      tools to place such investigations in context, they will continue to be
      susceptible to the rhetoric of proselytisers such as Gournay.

PMID- 9171570
TI  - Feigned mental disorder in prisoners referred to forensic mental health services.
AB  - This paper describes a study that aimed to identify the extent to which feigning
      of mental illness represents a significant problem in prisoners referred to a
      medium secure unit. A clinical method was used to assess the prisoners, employing
      the Structured Interview of Reported Symptoms (SIRS) and selected Minnesota
      Multiphasic Personality Inventory-2 (MMPI-2) validity indices. Stringent criteria
      were used to classify 60 consecutive referrals to a secure unit as feigning
      mental disorder or not. In addition, the study examined characteristic
      differences, on a number of selected variables, between those prisoners who feign
      and those who respond honestly. The personality profiles of prisoners who feign
      were also investigated. Analysis of data showed that 32% of the sample (P < 0.01)
      could be classified as fabricating or exaggerating symptoms of mental illness. It
      is suggested that such presentations may be more prevalent than previously
      considered. Few differences were observed between the groups on selected
      variables, although prisoners who feigned mental illness demonstrated
      significantly higher dependent and anxious (avoidant) personality types. The
      implications of the findings are discussed in relation to available models of
      feigned presentations.

PMID- 9171571
TI  - Measuring outcomes in the treatment of alcohol dependency.
AB  - The selective promotion of clinical services which have proven effectiveness is a
      movement that is gaining momentum within healthcare. Outcome evaluation in
      treatment services for alcohol dependency is given as an example of the
      methodological issues associated with the establishment of clinical efficacy. It
      is argued that the adoption of clear protocols for assessment, treatment and
      outcome are a prerequisite of the process. There are costs associated with in
      house follow-up studies but the benefits of feedback are evident for patients and
      for staff providing their care. Although exposing service providers (and
      commissioners) to the possibility of negative feedback, outcome evaluation in the
      treatment of alcohol dependency should be an integral part of provision. The
      principle of systematic assessment of efficacy applies to healthcare provision
      generally and should include management, teaching, purchasing and policymaking.

PMID- 9171572
TI  - Normalization: analysis and application within a special hospital.
AB  - The concept of normalization has provided the underpinning philosophy in learning
      disability nursing for more than 20 years. Despite its universality, however, it
      remains widely misinterpreted and misunderstood, and such problems are likely to
      be compounded within the context of secure services. This paper analyses the
      concept of normalization in an attempt to clarify the misconceptions and to
      stimulate a more widespread application of its principles. A theoretical review
      precedes an ethnographic examination within a forensic learning disability
      service. A final analytical phase then suggests directions for future
      developments.

PMID- 9171573
TI  - The patient's daily activities in acute psychiatric care.
AB  - This study is part of a research project entitled: 'Towards patient-focused
      nursing on an acute psychiatric ward'. The aim of the project is to describe the
      changes taking place in nursing activities during a research project. This paper
      is a qualitative analysis of the patient's daily activities in acute psychiatric
      care. The data were collected by observing, selectively, seven patients for 61 h.
      The constant comparative method was used in data analysis. On the basis of the
      data analysis, the categories listed below were identified. 1 The core category
      of the patient's daily activities was 'being a patient'. 2 Being a patient mainly
      consisted of being alone without meaningful activities. 3 Participating in the
      daily routines of the ward consisted of being alone while being together with
      others. 4 Being together was initiated by either the patient or the nurse. The
      aim of being together was to satisfy the acute basic needs of the patients. 5
      Being together on the initiative of the nurse meant participating in the daily
      routines of the ward. Because the data were collected by observation, no insight
      into the patients' desires, expectations and thoughts could be presented. The
      findings challenged the nursing staff to develop a more therapeutic daily routine
      in acute psychiatric care. It was also of importance to change the patients'
      meaningless existence into a meaningful participation in the daily activities on
      the ward.

PMID- 9171574
TI  - Monitoring the outcome of case management and community care: the care programme
      approach support system (CPASS).
AB  - This study reports the findings of an audit of community care outcomes, for the
      seriously mentally ill, in one health district in the UK. An innovative community
      care and case management system for this client group was introduced in 1993. As
      part of that organizational change, data were collected continuously on the
      severity of client problems. A satisfaction survey of a random sample of clients
      and carers has now also been completed. This report is thus able to compare
      feedback on service performance using two methodologies. As both the problem
      rating scales and the satisfaction surveys were designed specifically to cover
      the same 12 domains of client problems, data from both can be integrated easily.
      The 12 domains also structure the assessment tools used by nurses and social
      workers, and form the basis of minimum standard specifications of community care
      provision. Selected data from the audits are presented, and the utility of these
      results for further local service developments are assessed. The methodology used
      can be recommended as a means of continuous audit of joint services for those
      with serious and enduring mental health problems.

PMID- 9171576
TI  - The administration of PRN medication by mental health nurses.
AB  - The use of PRN or 'as required' medication by mental health nurses is an
      important, yet little explored aspect of psychiatric inpatient care. In a survey
      of 100 inpatients in Canada (Craven et al. 1987), it was reported that 88% had
      been prescribed PRN medication. The most frequently administered drugs were
      antipsychotics, anticholinergics, and benzodiazepines. Similar results were found
      in a study by Walker (1991). Craven et al. (1987) also highlight that people over
      the age of 50 are more likely to be given PRN medication, and suggest that gender
      and legal status do not influence administration. Vitello et al. (1991), in a
      study of factors affecting the administration of PRN medication on a children's
      psychiatric unit, demonstrated that 91% of administrations were given orally
      (compared to 9% via intramuscular injection); however it is unclear if this
      finding can be generalized to an adult psychiatric setting. Mental health nurses'
      reasons for administering PRN medication have not been examined.

PMID- 9171575
TI  - A descriptive study of multidisciplinary mental health staff moving to the
      community: the demographic and educational issues.
AB  - Mental health care philosophy has moved from the containment of patients within
      institutions to the integration of clients within the community. 'Caring for
      People' (a Department of Health report) and the subsequent legislation enshrined
      the philosophical shift in law. Previous policy reports had indicated that staff
      required training to move from hospital-based service to a community-based
      service, but did not propose content, and no systematic study of the needs of
      mental health staff has been carried out. Therefore, this study aimed to identify
      the skill and information needs of a group of multidisciplinary staff in
      preparation for the movement from hospital to community settings. The study
      design was a descriptive survey sampling of a total multidisciplinary population
      in Scotland. Data were collected using questionnaires and semistructured
      interviews with a small volunteer subsample of respondents. This paper presents
      the first set of study findings related to the demographic and educational
      issues. Differences between hospital and community staff and between health care
      assistants and qualified staff are demonstrated for demographic and educational
      factors. Proposals are made for managers, professionals, educators and
      researchers.

PMID- 9171577
TI  - A survey of patients' preferences for mixed- or single-sex wards.

PMID- 9171578
TI  - Developing nursing skills in an intensive case management service.

PMID- 9171579
TI  - The One-Stop Dementia Care project.

PMID- 9171580
TI  - What to do with certainty: a response to Kevin Gournay.

PMID- 9171581
TI  - A critique of Gournay's position on nursing theory and models.

PMID- 9171582
TI  - Recognition of women's needs.

PMID- 9171583
TI  - Childbirth in eastern Europe.
AB  - Women's experiences of pregnancy and childbirth in the countries of central and
      eastern Europe are explored in this paper. A capacity building intervention
      programme in St Petersburg, Russia, which attempts to reform practices within the
      city, is described. The difficulties inherent in integrating differing cultural
      approaches to childbirth are highlighted.

PMID- 9171584
TI  - What is the normal pattern of uterine involution? An investigation of postpartum
      uterine involution measured by the distance between the symphysis pubis and the
      uterine fundus using a paper tape measure.
AB  - OBJECTIVE: To describe normal postnatal uterine involution in a small sample of
      healthy primiparous women, and estimate the proportion who have a decline in the
      distance between the symphysis pubis and the uterine fundus (S-FD) slow enough to
      have the potentiality to trigger further clinical action, using currently
      accepted criteria for intervention. SETTING: A maternity unit in the south of
      England that has approximately 6000 deliveries per annum and the related
      community areas. METHODS: Daily measurement of the S-FD was carried out in 28
      healthy women from within 18 hours of delivery until the uterine fundus was no
      longer palpable abdominally. Graphs showing the daily measurements and
      correlation coefficients were used to describe involution. The proportion of
      healthy women who would have been identified as healthy by the screening method
      was estimated (its specificity). FINDINGS: Considerable variability was found in
      the pattern of uterine involution that was experienced by the women who had a
      normal puerperium. The measurement of the S-FD has a low specificity with only 6
      of the 28 women (21.4%; 95% CI 8.3% to 40.9% having had no episodes of the S-FD
      declining slowly (less than 1 cm over three days). There was a weak, positive
      correlation between the S-FD measurement on day one and the day on which the
      uterus ceased to be palpable (r = 0.426, P = 0.03). No relationship was found
      between method of baby feeding and the day on which the uterus ceased to be
      palpable. IMPLICATIONS FOR PRACTICE: The measurement of S-FD using a paper tape
      measure should not form part of routine postpartum assessment.

PMID- 9171585
TI  - Adolescents' ideas about the health of the fetus.
AB  - OBJECTIVE: To determine the preponderance of ideas in adolescents about the
      relationship between maternal habits and the health of the fetus. DESIGN:
      Quantitative survey using a precoded questionnaire, the content of which was
      derived from the transcripts of interviews and the responses to open-form
      questionnaires. SETTING: North West Region Health Authority area, UK.
      PARTICIPANTS: 674 adolescents in British National Curriculum Year 10 (age 14/15)
      from 6 Community Comprehensive Schools. FINDINGS: Most of the adolescents were
      aware of the dangers to the fetus of alcohol and smoking, including passive
      smoking. However, they were less aware of the potential hazards during pregnancy
      of eggs (Salmonella), soft cheeses (Listeria), liver (Vitamin A excess) or
      handling cats (Toxoplasmosis). Most of the respondents thought that the optimum
      time to initiate actions for a healthy pregnancy was when pregnancy had been
      confirmed, suggesting that the benefits of preconceptual care are not well known.
      KEY CONCLUSIONS: Adolescents lack knowledge about some of the specific hazards to
      the fetus of maternal diet and behaviour during pregnancy and are unaware of the
      importance of the early stages of pregnancy in this context. IMPLICATIONS: There
      is a need for the provision of education about the importance of a healthy
      maternal lifestyle before conception and during early pregnancy for adolescents.
      Midwives may have a proactive role in such education, but should be aware that
      young people may have specific areas of ignorance and misconceptions which will
      need addressing.

PMID- 9171586
TI  - Successful breast feeding in spite of early mother-baby separation for neonatal
      care.
AB  - OBJECTIVE: To study the effects on breast feeding duration of mother-baby
      separation after birth, owing to full-term babies' care in a neonatal unit for a
      maximum of six days. DESIGN: Retrospective review of medical records and
      telephone interviews with mothers. SETTING: A level II and III NICU in a
      University Hospital. PARTICIPANTS: 148 mother-baby pairs in a separated group and
      3516 in a comparison group. MAIN OUTCOME MEASURES: Breast feeding success is
      defined as the duration of exclusive and partial breast feeding. FINDINGS: There
      were no differences in breast feeding duration between babies in the separated
      group and the comparison group. More than 70% of the babies in both groups were
      breast fed exclusively after two months and more than 50% for more than four
      months. In the separated group delays in physical contact, first suckling and
      regular breast feeding, and duration of separation were not associated with
      shorter duration of breast feeding. Mixed feeding, both breast and bottle at the
      time of discharge from hospital, and baby diagnosis of hypoglycaemia had a
      negative impact. Maternal level of education was also associated with the breast
      feeding outcome. CONCLUSIONS: Although every possible effort should be made to
      avoid mother-baby separation, women can be reassured that separation, because of
      their or the baby's medical condition during the first days after birth, need not
      be considered an obstacle to successful breast feeding.

PMID- 9171587
TI  - Women's experience of transfer from community-based to consultant-based maternity
      care.
AB  - OBJECTIVE: To investigate women's experience of transfer from community-based to
      consultant obstetric care. DESIGN: Semi-structured interviews three to eight
      weeks postnatally, which were taped, transcribed and analysed according to
      grounded theory. SETTING: Community-based maternity service, Sheffield, England.
      PARTICIPANTS: Twelve women who had been transferred to consultant care in late
      pregnancy or labour. MAIN OUTCOME MEASURES: Categories which described and
      explained women's experience and that could be validated by checking back against
      the interview data. FINDINGS: There was a strong potential for disappointment
      with their labours, but this could be ameliorated by certain aspects of care,
      namely information and explanation, debriefing, and continuity of care.
      CONCLUSION: Transfer is an inevitable consequence for a proportion of community
      booked women but need not be a negative experience, with appropriate care.

PMID- 9171588
TI  - Jewish and Celtic attitudes to breast feeding compared.
AB  - OBJECTIVE: To examine reasons for the high rate of breast feeding among one UK
      ethnic group (Jews) and the low rate among Celtic (Scots and Irish) populations.
      DESIGN: A manual literature search of ethnic variation in breast feeding rates in
      the UK was conducted over several years. A computerised search yielded 31
      additional references. Seven of these were added. ANALYSIS: Positive Jewish
      attitudes to breast feeding were underpinned by scriptural references, and rates
      of breast feeding were found to be especially high among Orthodox samples in the
      UK and Israel. Low Scottish and Irish rates appear to reflect prudishness,
      fashion, and possibly poor health. Reasons for falling rates among these
      populations in the twentieth century were not clear. IMPLICATIONS FOR PRACTICE:
      Health education needs to address cultural attitudes throughout society if
      effective change is to be introduced, and the overall rate of breast feeding is
      to be increased.

PMID- 9171589
TI  - Myths and facts...about osteoporosis.

PMID- 9171590
TI  - Catheter selection: choosing the right size.

PMID- 9171591
TI  - What to do if you're exposed to HIV. Learn the latest about postexposure
      prophylaxis.

PMID- 9171592
TI  - Nursing the Net. Exploring newsgroups.

PMID- 9171593
TI  - A failure to communicate. Conflicting orders lead to a serious patient injury.

PMID- 9171594
TI  - Confronting a tempest. Acute leukemia.

PMID- 9171595
TI  - 10 tips for keeping hope alive.

PMID- 9171596
TI  - Return demonstrations. How to validate patient education.

PMID- 9171597
TI  - The take on telemedicine.

PMID- 9171598
TI  - Managing hypovolemia.

PMID- 9171599
TI  - What to do about PICC line problems.

PMID- 9171600
TI  - Would Connie ever take her medication?

PMID- 9171601
TI  - Alzheimer's drug update: learn what drugs look promising.

PMID- 9171603
TI  - Understanding the ins & outs of diuretic therapy.

PMID- 9171602
TI  - Anaphylaxis.

PMID- 9171604
TI  - Dialysis choices. Turning the tide in acute renal failure.

PMID- 9171606
TI  - Would you help a patient die?

PMID- 9171605
TI  - Assessing pupillary responses.

PMID- 9171607
TI  - Sadie wouldn't let go of her pain.

PMID- 9171608
TI  - Automatic flush feeding pumps.

PMID- 9171609
TI  - Ventilator-associated infections. Reducing the risks. Part I.

PMID- 9171610
TI  - Nursing and the press.

PMID- 9171611
TI  - Why isn't patient-controlled analgesia relieving the pain?

PMID- 9171613
TI  - A guide to armchair education. How to pursue a bachelor's degree without leaving
      home (almost).

PMID- 9171612
TI  - Fenfluramine and phentermine.

PMID- 9171614
TI  - Mentoring nursing students.

PMID- 9171615
TI  - Listening to Charlie. Would this private man ever break his silence?

PMID- 9171616
TI  - Myths and facts...about grief.

PMID- 9171617
TI  - Browsing the World Wide Web.

PMID- 9171618
TI  - Documenting discharge teaching.

PMID- 9171619
TI  - Your guide to gloves. Learn when to use--not abuse--a good thing.

PMID- 9171620
TI  - Taking the right medications at the right time.

PMID- 9171621
TI  - Crossing cultural boundaries.

PMID- 9171622
TI  - Administering abciximab. A new drug for preventing coronary restenosis.

PMID- 9171623
TI  - Giving common respiratory drugs.

PMID- 9171624
TI  - Stemming the tide of acute pulmonary edema.

PMID- 9171625
TI  - A quick guide to converting rapid rhythms. When seconds count, use this chart to
      guide treatment choices.

PMID- 9171627
TI  - Brain attack. Treating acute ischemic CVA.

PMID- 9171626
TI  - Emergency childbirth.

PMID- 9171628
TI  - My Bonnie. When a nurse befriends a dying patient, do the gains outweigh the
      losses?

PMID- 9171629
TI  - Ventilator-associated infections. Part II. Reducing the risks.

PMID- 9171630
TI  - Tomorrow's LPN. Understanding the role.

PMID- 9171631
TI  - Hope. Offering comfort and support for dying patients.

PMID- 9171632
TI  - Career development handbook.

PMID- 9171633
TI  - How to record an accurate 12-lead ECG.

PMID- 9171634
TI  - Assessing bowel sounds.

PMID- 9171636
TI  - Mary's prayer.

PMID- 9171635
TI  - Risperidone and neuroleptic malignant syndrome. Recognizing a potentially fatal
      condition.

PMID- 9171637
TI  - Central lines: controversies in care.

PMID- 9171638
TI  - Your role in thoracentesis.

PMID- 9171639
TI  - How to become a master juggler. Try these simple steps for managing multiple
      priorities.

PMID- 9171640
TI  - The color of fear. Were this patient's feelings more than skin-deep?

PMID- 9171641
TI  - Breaking out of the box.

PMID- 9171642
TI  - Maintaining a PICC line: what you should know.

PMID- 9171643
TI  - Myths and facts...about amputations.

PMID- 9171646
TI  - Infusion pump mishap.

PMID- 9171644
TI  - How to stop the pox.

PMID- 9171647
TI  - Monitoring blood glucose levels at the bedside.

PMID- 9171645
TI  - Documenting psychiatric and behavioral outcomes.

PMID- 9171648
TI  - Traveling the Web with search engines.

PMID- 9171649
TI  - Postmortem care: healing's first step.

PMID- 9171650
TI  - Assessing altered mental status.

PMID- 9171652
TI  - Joint bleeding in hemophilia.

PMID- 9171651
TI  - Basic life support.

PMID- 9171653
TI  - Informatics certification. Putting your technology know-how to work.

PMID- 9171654
TI  - Recognizing when long QT intervals mean trouble.

PMID- 9171655
TI  - How to administer t-PA in acute ischemic stroke.

PMID- 9171656
TI  - Investigating postoperative atrial fibrillation.

PMID- 9171657
TI  - Heart failure: helping your patient help herself.

PMID- 9171658
TI  - Easing the discomfort after breast surgery.

PMID- 9171659
TI  - Caught in the middle of a family fight.

PMID- 9171660
TI  - How would you handle this request for assisted suicide?

PMID- 9171661
TI  - Venous air embolism.

PMID- 9171662
TI  - Caring for a patient with colon cancer.

PMID- 9171663
TI  - Improving your leadership skills. Seven common pitfalls to avoid.

PMID- 9171664
TI  - Pain management handbook.

PMID- 9171665
TI  - Putting a stop to shame.

PMID- 9171666
TI  - Advance directives. Honoring your patient's end-of-life wishes.

PMID- 9171667
TI  - Atrial fibrillation.

PMID- 9171668
TI  - Using a personal ventilation mask. Your protection from infection.

PMID- 9171669
TI  - Are your patients taking their medications correctly?

PMID- 9171670
TI  - Assessing for bladder distension.

PMID- 9171671
TI  - Handling inappropriate sexual behavior with confidence.

PMID- 9171672
TI  - Patient abandonment.

PMID- 9171673
TI  - Controlling pain. Managing chronic cancer pain.

PMID- 9171674
TI  - Herbal remedies and seizures.

PMID- 9171676
TI  - Preparing for a smooth return to school.

PMID- 9171675
TI  - A fresh perspective.

PMID- 9171677
TI  - Keeping hope alive.

PMID- 9171678
TI  - Double vision.

PMID- 9171679
TI  - Oncology case management linking structure and process with clinical and
      financial outcomes.
AB  - Case management programs have emerged in a variety of models. Current literature
      about the structure and process of case management programs has not always
      clearly described linkages with outcomes. Therefore, the purpose of this article
      is to describe a case management program, apply the model with oncology patients,
      and then to clarify the structure and process that the authors believe are
      correlated strongly with both clinical and financial indicators of quality.
      Planning for the case management program involved interdisciplinary inpatient
      staff and personnel from the ambulatory oncology clinics. After program
      implementation, data on patients with a diagnosis of chemotherapy without acute
      leukemia (DRG 410) were collected throughout 1 year (March 1995-February 1996).
      Results indicated a reduction in length of stay and side effects of chemotherapy
      linked to the improvement in process. The primary recommendation to nurse
      managers who are considering a case management program is to carefully decide on
      a structure and process that can be formalized before the program is implemented.

PMID- 9171680
TI  - The needs, uses and issues surrounding computerized variance data analysis.

PMID- 9171681
TI  - Fetal maternal case management.
AB  - Multiple transfers, multiple specialists, and an unpredictable hospital course
      can result in ineffective communications among patients and the health care team.
      Complex care requirements easily become fragmented and lack coordination, thus
      overwhelming a family and even a well-intended multidisciplinary care delivery
      team. Because of this concern, the Greater Kansas City Fetal Board originated and
      implemented a new nursing case management model for high-risk obstetric and fetal
      patients. Fetal maternal case management crosses traditional hospital and
      provider boundaries with the pregnant patient. Case management allows parents to
      identify treatment options, and then create with specialists a plan of care. Case
      managers work with parents to identify support systems and explore parental
      preferences. The purpose of this article is to describe the fetal maternal case
      management model. Readers will better understand the need and value of such a
      program, as well as gain insight into how to facilitate fetal maternal case
      management.

PMID- 9171682
TI  - Case management improves congestive heart failure outcomes.

PMID- 9171684
TI  - A case for case management: marketing the service to physicians.

PMID- 9171683
TI  - Care coordination in an academic medical center.
AB  - Care coordination/case management models provide a method to measure expenditures
      within the context of health-care outcomes. High costs are predictable in a high
      skill, technology-intensive service industry such as academic medical centers. A
      care-coordination model provides a means to reduce the cost per case and
      influence patient satisfaction. In this article, the authors describe a Care
      Coordination Model for neurologically impaired patients in an academic medical
      center. The Care-Coordination Model serves as a structure for cost containment
      within a diagnostic reimbursement grouping (DRG) category and provides an
      opportunity to develop alternative care programs to support those disabled in
      their community setting. Clinical and financial outcomes are presented as well as
      follow-up in the form of a patient survey. The results demonstrate cost savings
      in several charge categories, a reduction in the length of stay, a reduction in
      the variation of clinical treatment, and an increase in patient satisfaction
      regarding discharge preparation.

PMID- 9171685
TI  - Hiring case managers: the role of the candidate and the interviewer.
AB  - Interviewing for a job and conducting an interview are two challenging tasks
      nurse case managers experience at some point in their nursing career. One way to
      overcome such challenges is through learning more about the interview process.
      For the nurse case manager, the reward of interviewing well is getting hired for
      the job; for the interviewer, it is selecting the best candidate for the job. In
      this article, the author discusses the roles of the candidate and the interviewer
      in the interview process. It provides those interested in becoming nurse case
      managers with tips, skills, and strategies for assuring a successful interview.
      It also presents administrators of case management programs with beneficial
      recommendations for improving their interviewing skills. In addition, it
      discusses the interview process for potential candidates for nursing case
      management roles from the time of preparing the resume and cover letter until
      after the interview is completed.

PMID- 9171686
TI  - Learning to be better caregivers: a new (fiscal) year's resolution.

PMID- 9171688
TI  - Communication 101.

PMID- 9171687
TI  - A model of collaboration: the Academic Practice Council.
AB  - If the profession of nursing is to survive in the changing health care delivery
      system, new models of collaboration between nursing education and nursing
      practice must be developed. Nursing is both an academic discipline and a practice
      profession. The historic dissonance between education and practice has never
      served the profession of nursing; the pressing challenge is to blend one with the
      other now. In an effort to respond to the demands of the discipline and
      profession of nursing, an academic institution and a health care delivery system
      developed a model of interagency collaboration. This article addresses historical
      perspectives, and evolution, structure, activities, evaluation, and future plans
      to the Academic Practice Council.

PMID- 9171689
TI  - Collaboration in research: testing the PIPC model on clinical and nonclinical
      outcomes.
AB  - This outcomes research used a collaborative framework between a college of
      nursing and a medical center to test the effects of the Partners in Patient Care
      delivery model (PIPC) on clinical and nonclinical outcomes. An experimental
      pretest-postest design was used to compare selected nonclinical outcomes and
      clinical outcomes of care in two patient units. Results showed that there were
      significant differences between units in the nonclinical outcomes of nurse
      satisfaction, salary costs, supply costs, and productivity as measured by
      documentation time. In addition, there were significant differences in the
      clinical outcomes of care in terms of patient satisfaction. No significant
      differences were found in number of falls, medication errors, and intravenous
      infections; however, when ratios of these indicators were examined in relation to
      patient days, significant differences in the medication error ratio and the fall
      ratio were revealed. The results indicate that the PIPC delivery model did have
      positive effects on patient satisfaction and nurse satisfaction but that there
      were increased costs and increased time spent in documentation on the pilot unit.

PMID- 9171690
TI  - Doing business with your patients: is it bad business?

PMID- 9171691
TI  - Caring in full circle: the legacy of Edith Honeycutt.
AB  - Edith Folsom Honeycutt, now retired, is the only staff nurse in the United States
      to be honored by a funded chair at a major university. In 1990, a chair of
      oncology nursing was established in her name at Emory University by the
      Metropolitan Atlanta Community Foundation. A life history method was used to
      examine the professional life of Edith Honeycutt through interviews and with a
      focus group of nurses who had worked with her. Three themes emerged: teaching by
      showing; expecting excellent practice; and investing in each other. A synthesized
      overall theme of "caring in full circle" was identified as the core descriptor.
      The findings of this study demonstrate how clinical education and expertise are
      shared and learned among staff nurses. Findings also suggest how nursing
      knowledge can be, and is, developed at the bedside. The connection between Emory
      University and Edith Honeycutt demonstrates an enduring link between a university
      setting and a practice arena.

PMID- 9171692
TI  - Confidentiality and computerized medical records.

PMID- 9171694
TI  - Patient satisfaction--is it the key?

PMID- 9171693
TI  - Collaborative partners in nursing education: a preceptorship model for BScN
      students.
AB  - This article depicts and describes five significant steps in the process of
      establishing and maintaining a nursing student preceptor programme in a
      psychiatric unit. Specific collaborative relationships, roles, strategies,
      important qualities, and suggestions are identified to enhance the success and
      contributions of each of the three learning partners--student, preceptor, and
      clinical faculty tutor. The steps and processes highlighted in this model are
      based on the actual experience of a nurse educator in a university school of
      nursing, in collaboration with the director of psychiatry (also a nurse) at a
      community hospital in southern Ontario, Canada. The authors jointly share their
      perceptions of the strengths, limitations, and mutual benefits experienced
      throughout all phases of this collaborative partnership. In addition, student and
      preceptor feedback on the placement are described, demonstrating the usefulness
      of ongoing feedback from all the participants. This article will be of interest
      to other nurse educators planning to initiate and maintain clinical preceptorship
      programs.

PMID- 9171695
TI  - The last one standing is the winner?

PMID- 9171696
TI  - Mandibular elongation by bone distraction: treatment for mandibular hypoplasia
      with Robin sequence.
AB  - Robin sequence is the combination of micrognathia (small jaw), retrognathia
      (posterior displacement of the chin) and glossoptosis (falling backward of the
      tongue) in newborns, and is often found in combination with clefting of the
      palate. Mandibular elongation by bone distraction, described in this article, is
      one treatment for mandibular hypoplasia with Robin sequence.

PMID- 9171697
TI  - The use of tissue expansion for the treatment of burn scar alopecia.
AB  - Tissue expansion is an ideal reconstructive procedure for burn scar alopecia.
      Donor tissue is generated in situ, allowing for the use of hair-bearing tissue to
      reconstruct an area of alopecia. The process of tissue expansion results in a
      redistribution of the remaining hair follicles to replace the area of alopecia.

PMID- 9171698
TI  - Healing the world's forgotten children: an international nursing experience.
AB  - An increasing number of nurses are volunteering to participate in overseas
      missions. The focus of many of these missions is to perform plastic and
      reconstructive surgery on children. Nursing practice within the health care
      system of a third-world country is both exciting and challenging. Since 1978,
      Operation Rainbow has given nurses the opportunity to experience perioperative
      nursing in international settings. Although filled with many hardships,
      international nursing can be a very rewarding experience.

PMID- 9171699
TI  - Standards of clinical practice for plastic surgical nursing. American Society of
      Plastic and Reconstructive Surgical Nurses.

PMID- 9171700
TI  - Comparisons of pain ratings from postoperative children, their mothers, and their
      nurses: a research critique.

PMID- 9171701
TI  - Digital imaging for plastic and reconstructive surgery.
AB  - Digital imaging provides many benefits to plastic surgical practice. While
      problems arise, there are many advantages. The ethical use of digital imaging may
      be a cost-effective, valuable asset to the practice of plastic surgery.

PMID- 9171702
TI  - Personnel records: a management responsibility.

PMID- 9171703
TI  - CPSN pass rate exceeds 95%.

PMID- 9171705
TI  - Basic principles of aseptic technique.

PMID- 9171707
TI  - The introduction of collaborative care plans.
AB  - Collaborative care planning and documentation should produce higher standards of
      care for patients. The collaborative approach should also improve teamwork and
      create greater understanding between different disciplines.

PMID- 9171706
TI  - Prescribed drugs and iatrogenic disease.
AB  - Prescribed drugs can cause side-effects and adverse reactions and can interact
      with other medications. Factors such as age, disease and idiosyncratic responses
      can cause drug intolerance in some people. Nurses must be able to provide
      patients with appropriate information to ensure the safe administration of their
      drugs.

PMID- 9171708
TI  - Self-management of asthma.
AB  - Many patients with asthma are able to monitor and manage their condition
      successfully with support. Monitoring of peak expiratory flow can help provide
      information on an individual's condition. Information and education are vital in
      reducing mortality and morbidity in asthma.

PMID- 9171709
TI  - Problems affecting Asian women with diabetes.
AB  - Diabetes is common among British Asians, who require appropriate advice and
      information. Cultural and language difficulties may create a barrier to
      information. A sensitive, knowledgeable approach and the use of information
      leaflets and videos in appropriate languages can help overcome this barrier.

PMID- 9171710
TI  - The role of the neonatal family care specialist.
AB  - The role of neonatal family care specialist was developed to meet the demands of
      an ever-changing health service. Families are empowered and encouraged to take
      control by the provision of clear, concise information. Audit and evaluation are
      vital in assessing the effectiveness of the new role in order to maintain a high
      standard of appropriate care.

PMID- 9171711
TI  - Clostridium difficile.

PMID- 9171712
TI  - Chronic fatigue syndrome.

PMID- 9171713
TI  - Incorporating the named nurse concept into care.
AB  - The named nurse concept stresses the importance of individualised care for
      patients. The concept is compatible with methods of nursing that put emphasis on
      the individual relationship with patients, such as primary nursing and team
      nursing. With sufficient resources, the named nurse is a suitable concept to
      apply in the organisation of care delivery in mental health nursing.

PMID- 9171714
TI  - Health and stress. Part 1. Public health and personal health.

PMID- 9171715
TI  - Blood glucose monitoring devices.
AB  - Blood glucose monitoring can enable people to control their diabetes. People with
      diabetes will be motivated to continue monitoring only if it is seen to be
      effective. Patient education will significantly influence people's attitude to
      blood glucose monitoring, and must reflect individual needs and circumstances.

PMID- 9171716
TI  - Risk assessment tools.

PMID- 9171717
TI  - Defining euthanasia.

PMID- 9171718
TI  - Psychosexual aspects of stoma-care nursing.

PMID- 9171719
TI  - Muscle tone abnormalities.
AB  - Rehabilitation nurses frequently encounter clients with neurological disorders
      that adversely affect muscle tone. By understanding the physiological etiology of
      abnormal muscle tone, individual practitioners can design nursing interventions
      for various care settings that appropriately protect clients from injury and that
      can help clients and caregivers learn effective techniques for managing muscle
      tone problems. This article explains muscle tone abnormalities in detail and
      offers insight into how rehabilitation nurses can play a key role in managing
      clients' alterations in muscle tone.

PMID- 9171720
TI  - Clinical nursing judgment related to reducing the incidence of falls by elderly
      patients.
AB  - The incidence of falls among elderly patients has been and continues to be a
      major challenge for nurses. Falls add physical injury and mental stress to
      patients' existing health problems, are a deterrent to rehabilitation, and
      increase healthcare costs. This study describes the variables that nurses
      identify as influencing their clinical decision making and the nursing behaviors
      associated with preventing patient falls. The study was grounded in the theory
      that discretionary nursing behaviors are related to nursing expertise, and the
      study was guided by the assumption that such behaviors are proactive and
      anticipatory. An analysis of interviews of registered nurses (n = 14) working on
      a geriatric rehabilitation unit in a medical center in Ohio focused on the zones
      of association and the contextual meanings of language used by the nurses when
      discussing patient falls. Four themes emerged: the reasons for patient falls,
      identifying patients who are likely to fall, preventing falls, and nurses'
      feelings when patients fall.

PMID- 9171721
TI  - Helping the client with chronic disability achieve high-level wellness.
AB  - Clients with chronic disability often define themselves in terms of their sick
      role. Today, many healthcare professionals and laypersons alike prefer to view
      the individual as a unified whole striving toward high-level wellness. Thus, a
      client may be diagnosed with a physical illness, a chronic illness, or a
      disability but may still work to attain high-level wellness by functioning in an
      integrated way with the environment. This article describes the client with
      chronic disability in relation to high-level wellness and provides techniques
      nurses can use to facilitate a client's positive adjustment.

PMID- 9171723
TI  - A study of the psychosocial characteristics of patients in a geriatric
      rehabilitation unit in Israel.
AB  - This study characterizes the demographic backgrounds of patients in an Israeli
      geriatric rehabilitation unit, determines the factors associated with their
      family relationships and the instrumental support they received, and emphasizes
      the importance of social roles as a personal resource. The study population
      consisted of 336 low-income Jews, all of whom were immigrants. Virtually all of
      the subjects had a small, close support network composed mainly of their children
      and spouses. Their children were the most important source of instrumental
      support during their hospitalization. The subjects' sources of instrumental
      support prior to hospitalization varied, depending upon their age, gender,
      marital status, and social roles. Social exchange theory provided a framework for
      explaining their social roles. Factors found to be predictors of good family
      relationships were marital status, living arrangements, instrumental support,
      social roles, and educational level.

PMID- 9171722
TI  - An examination of the self-care needs of clients with rheumatoid arthritis.
AB  - Investigators used Orem's self-care deficit theory to guide their examination of
      the needs of clients with rheumatoid arthritis. Several research questions, which
      were guided by the proposition that universal self-care requisites are influenced
      by a person's age, gender, and health state, were addressed. Interviews with 59
      clients with rheumatoid arthritis were tape recorded, and transcripts of the
      interviews were analyzed by two experts using assigned codes of universal self
      care requisites (USCRs). The most frequently reported USCRs for these clients
      with rheumatoid arthritis were the maintenance of a balance between activity and
      rest (83%), the promotion of normalcy (66%), and prevention of hazards (58%).
      Clients' health state and age, but not their gender, affected USCRs. The clinical
      and theoretical implications of the findings are described in light of clients'
      rehabilitation.

PMID- 9171724
TI  - Tea time.

PMID- 9171725
TI  - There is a need for more rehabilitation nurses in home care practice.

PMID- 9171726
TI  - RAP: a Restraint Alternative Protocol that works.

PMID- 9171727
TI  - Acupuncture: the patient doesn't move around.

PMID- 9171728
TI  - Cardiac rehab: for spouses, too.

PMID- 9171729
TI  - Pulse oximetry--at your fingertips.

PMID- 9171730
TI  - Resume writing in a wired age.

PMID- 9171731
TI  - Conscious sedation. A primer.

PMID- 9171732
TI  - Your patient is deaf, now what?

PMID- 9171733
TI  - Knowing the signs.

PMID- 9171734
TI  - When the trauma patient is pregnant.

PMID- 9171735
TI  - Use research to weigh the alternatives.

PMID- 9171736
TI  - Shedding some light on psychiatric care issues.

PMID- 9171737
TI  - Is your patient really pain-free?

PMID- 9171738
TI  - Taking a chance.

PMID- 9171739
TI  - Bowel ischaemia after aortoiliac surgery.

PMID- 9171740
TI  - The magnetic resonance operating theatre.

PMID- 9171741
TI  - Open versus closed establishment of pneumoperitoneum in laparoscopic surgery.
AB  - BACKGROUND: Closed laparoscopy, employing a Veress needle and blind insertion of
      the first trocar, is favoured by most laparoscopic surgeons. The potential danger
      of this technique is the occurrence of visceral or vascular injury. Establishment
      of pneumoperitoneum by an open technique using a blunt-tipped trocar may be a
      safer alternative. METHODS AND RESULTS: Retrospective review of the literature
      and the authors' experience was used to compare closed and open laparoscopy. Data
      on closed laparoscopy in 489335 patients and on open laparoscopy in 12444
      patients were culled. Rates of visceral and vascular injury were respectively
      0.083 and 0.075 per cent after closed laparoscopy, and 0.048 per cent and zero
      after open laparoscopy. Mortality rates after closed and open laparoscopy were
      respectively 0.003 per cent and zero. Pearson chi 2 analysis demonstrated a
      statistically significant difference in terms of visceral and vascular injury
      between closed and open laparoscopy (P = 0.002); there was no such difference for
      mortality rates. CONCLUSION: Open establishment of pneumoperitoneum is advocated
      in laparoscopic surgery because it is safer than the closed method.

PMID- 9171742
TI  - Blunt injury to the supra-aortic arteries.
AB  - BACKGROUND: Blunt trauma causing injury to the vessels of the aortic arch is
      uncommon but may be attended by serious consequences. Most surgeons will
      experience only an occasional case and will need to rely on published literature
      for guidance. METHODS: A Medline search over 1986-1995 was carried out using the
      following keywords: brachiocephalic trunk, common carotid artery and subclavian
      artery; injury was used as a subheading. RESULTS AND CONCLUSION: After the aortic
      isthmus, the innominate is the most commonly injured artery in the chest.
      Whatever the site of an arterial lesion, however, angiography is the diagnostic
      test of choice. Some vascular lesions are relatively benign and may be managed
      without operation; this form of management may also be appropriate if there is
      severe associated neurological injury. Otherwise, operation using an approach and
      technique suited to the site of the injury is advocated.

PMID- 9171743
TI  - Analysis of randomized controlled trials in laparoscopic surgery.
AB  - BACKGROUND: Randomized controlled studies of surgical procedures are difficult,
      but can be done to acceptable standards. There are few published objective
      assessments of such trials. METHODS: The original articles that involved a
      randomized controlled trial including at least one laparoscopic procedure were
      reviewed and evaluated with special interest in their methodology. An assessment
      form containing 11 generic questions and three additional criteria (assessment of
      quality of life, cost analysis and laparoscopic experience required) was used.
      Forty trials were retrieved including 12 on cholecystectomy, 12 on hernia repair
      and 12 on appendicectomy. Each trial was scored by two assessors. RESULTS: The
      agreement among the two independent assessors was very good. Six of the trials
      were well conducted but 22 had a poor score. The trials on cholecystectomy were
      scored the best in contrast to those on hernia repair or appendicectomy. Few
      trials provided an adequate prospective calculation of the sample size, an
      unbiased assessment of endpoints, evaluation of the quality of life and a study
      of the economic aspects. CONCLUSION: Readers should be cautious when interpreting
      the results of some of these trials and their impact on daily surgical practice.

PMID- 9171744
TI  - Abdominal wall hernia in autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common
      cause of renal impairment with a number of well recognized extrarenal
      associations. A high incidence of abdominal wall hernia was noted in patients
      with ADPKD. METHODS: A retrospective review of the notes of all patients with
      ADPKD on the South Wales renal replacement therapy database was performed. These
      patients were compared with age- and sex-matched patients with renal failure but
      without ADPKD and with general surgical patients. RESULTS: The prevalence of
      hernia in patients with ADPKD was 38 of 85 (45 per cent) compared with seven of
      85 (8 per cent) for other forms of renal failure and three of 85 (4 per cent) for
      general surgical controls (P < 0.001). There were significantly greater numbers
      of inguinal (P < 0.001), incisional (P = 0.019) and paraumbilical (P = 0.007)
      hernias in patients with ADPKD compared with the other two groups. CONCLUSION:
      These results show a significantly greater incidence of hernia, which could be an
      additional manifestation of the underlying defect in extracellular matrix
      production identified in patients with ADPKD.

PMID- 9171745
TI  - Methods of replacing blocked hepatic artery catheters.
AB  - BACKGROUND: Regional chemotherapy using hepatic artery catheters is one method of
      treating patients with colorectal liver metastases. A problem arises when the
      catheter occludes in patients who are responding to treatment. This report
      describes experience of replacing occluded hepatic artery catheters. METHODS:
      Some 108 patients with colorectal liver metastases had hepatic arterial catheters
      surgically implanted for regional chemotherapy. The catheter occluded in 17
      patients at a time when they were responding to treatment. Twelve catheters were
      replaced, of which seven were inserted retrogradely into the splenic artery, four
      were anastomosed end to side to the common hepatic artery via a saphenous vein
      graft and one was replaced in the patent gastroduodenal artery. RESULTS: The mean
      duration of catheter survival when a saphenous vein graft was used was 9.6 months
      compared with 2.5 months following retrograde insertion into the splenic artery.
      CONCLUSION: Replacement of hepatic artery catheters is possible and may be of
      benefit in patients whose catheters fail while they are responding to treatment.
      The use of a saphenous vein graft appears to be a more anatomical and therefore
      preferable method of replacement than retrograde splenic artery cannulation.

PMID- 9171746
TI  - Prospective study of hepatobiliary scintigraphy and endoscopic cholangiography
      for the detection of early biliary complications after orthotopic liver
      transplantation.
AB  - BACKGROUND: Biliary complications are a significant cause of morbidity and death
      after orthotopic liver transplantation (OLT). This study was a prospective
      evaluation of endoscopic retrograde cholangiography (ERC) and hepatobiliary
      scintigraphy (HBS), using 99mTc Mebrofenin, to detect early biliary complications
      following OLT. METHODS: One hundred consecutive patients who had OLT with a
      biliary duct-to-duct anastomosis were studied. Of these, 67 had both ERC and HBS
      performed within 30 days of OLT. Sensitivity, specificity and diagnostic accuracy
      of HBS in identifying biliary leak or stricture was calculated. RESULTS: Of the
      67 cholangiographies performed 45 were normal. In 22 patients there was
      radiological evidence of a leak (n = 14) or stricture (n = 8) which required
      further intervention in nine and four patients respectively. The sensitivity and
      specificity of scintigraphy for the detection of biliary leak after
      transplantation was 50 and 79 per cent and for biliary stricture 62 and 64 per
      cent respectively. No patient with normal scintigraphy required biliary
      intervention. Only six of 14 patients with biliary leaks and two of 20 with
      strictures suggested by scintigraphy required intervention. If both ERC and HBS
      reported leak or stricture, the intervention rate was considerably higher at five
      of seven leaks and two of five strictures. CONCLUSION: This study suggests that
      scintigraphy is a useful screening test for biliary complications after OLT, ERC
      is only necessary if HBS is abnormal.

PMID- 9171747
TI  - Outcome of surgery for chronic pancreatitis.
AB  - BACKGROUND: In patients with chronic pancreatitis, surgery is indicated for the
      management of intractable pain or for the treatment of complications. METHODS:
      Sixty-three consecutive patients (49 men and 14 women of median age 40 (range 20
      72) years) who had undergone surgery over an 8-year interval for chronic
      pancreatitis were studied. The mortality and morbidity rates associated with
      surgery were assessed and quality of life was reviewed based on relief of
      symptoms, analgesic use, employment and long-term sequelae. RESULTS: Forty-four
      patients (70 per cent) had alcoholic chronic pancreatitis. In 60 patients the
      principal indication for surgery was intractable pain. Eighteen patients had a
      duodenum-preserving resection of the pancreatic head (Beger operation); the other
      surgical procedures were Whipple resection (15), left-sided resection (13), total
      pancreatectomy (seven), pseudocystjejunostomy (five), pancreaticojejunostomy
      (one) and bypass procedures (four). The median inpatient stay was 12 days; 23
      patients had postoperative complications including one death (2 per cent). There
      was improved pain control (P < 0.001), a reduction in opiate analgesia use,
      increase in percentage weight gain (P < 0.01 at 2 years) and return to employment
      following surgery. Although there was an increase in diabetes mellitus and need
      for enzyme supplementation these were easily controlled. CONCLUSION: Surgery is
      an effective treatment in carefully selected patients with chronic pancreatitis
      but must be tailored to the pattern of disease in each individual.

PMID- 9171748
TI  - Laparoscopic cholecystectomy and the umbilicus.
AB  - BACKGROUND: Pre-existing umbilical defects may present technical problems in
      patients having laparoscopic surgery. Fascial defects may also occur after
      operation. Understanding the causes and mechanisms of herniation at laparoscopic
      port sites may help avoid potentially serious postoperative complications.
      METHODS: The incidence, management and potential complications of pre-existing
      and postoperative umbilical defects were studied in 870 patients undergoing
      laparoscopic cholecystectomy. RESULTS: The incidence of umbilical or
      paraumbilical defects was 12 per cent. The hernias were symptomatic in only 16.3
      per cent; the majority of patients were unaware of the defect. The umbilical port
      was established through, or directly adjacent to, the defect, allowing simple
      anatomical repair in 90 per cent, using absorbable sutures. The recurrence rate
      was 3.8 per cent; recurrence was usually caused by wound extension or infection.
      Incisional hernia occurred in 16 patients after cholecystectomy (1.8 per cent).
      Only one hernia developed at a port site other than the umbilicus. Risk factors
      associated with incisional hernia were wound extension in 12 patients, male sex
      in six, wound infection in five, diabetes in four, pre-existing umbilical hernia
      in four and acute cholecystitis in three. CONCLUSION: The significant incidence
      of umbilical defects in patients undergoing laparoscopic surgery calls for
      accurate diagnosis and good technique. The incidence of incisional hernia might
      be reduced by avoiding unnecessary wound extension and the use of non-absorbable
      sutures for defects larger than 2 cm and in men with umbilical hernia.

PMID- 9171749
TI  - Cholecystectomy and fistula closure versus enterolithotomy alone in gallstone
      ileus.
AB  - BACKGROUND: The management of gallstone ileus is controversial. This study
      compared the results of simple enterolithotomy with those of enterolithotomy,
      cholecystectomy and fistula closure. METHODS: A retrospective analysis was made
      of 25 patients with a mean age of 75 (range 55-84) years. Enterolithotomy was
      performed in 16 patients (group 1) and cholecystectomy and fistula closure were
      added in nine patients (group 2). RESULTS: The diagnosis was made before
      operation in 12 patients, and was associated with previous biliary disorder (P =
      0.03) and pneumobilia (P < 0.001). Postoperative morbidity occurred in eight
      patients in group 1 and in six in group 2. Three patients died in each group; all
      but one of the deaths were unrelated to the surgical procedure. There was no
      relationship between age and mortality, and patients in American Society of
      Anesthesiologists (ASA) classes III and IV did not have higher rates of morbidity
      or mortality than those in ASA classes I and II. CONCLUSION: Evidence from this
      study does not support one-stage enterolithotomy, cholecystectomy and fistula
      closure as the procedure of choice; simple enterolithotomy is appropriate in most
      patients. However, the one-stage procedure may be acceptable in patients at low
      risk.

PMID- 9171750
TI  - Chemical ablation of the gallbladder.
AB  - BACKGROUND: Chemical ablation of the gallbladder might avoid the need for surgery
      in elderly, unfit patients. This study examined the efficacy of various chemicals
      in destroying gallbladder mucosa. METHODS: Ninety-five per cent ethanol, 3 per
      cent sodium tetradecyl sulphate (STD), trifluoroacetic acid (TFA) 2 mol/l,
      tetracycline 50 mg/ml, 30 and 50 per cent phenol, and a mucosal exfoliant
      solution (compound ethylene diamine tetra-acetic acid) were tested for
      gallbladder ablation in rabbits. Histology was obtained 8 weeks after exposure to
      these chemicals. RESULTS: Thirty per cent phenol, tetracycline, TFA and ethanol
      when used as single agents were moderately effective in causing complete
      gallbladder mucosal obliteration, 50 per cent phenol caused a macroscopic burn of
      the entire gallbladder. The mucosal exfoliant solution and STD on their own did
      not cause mucosal destruction but had significantly enhanced efficacy when
      combined with 95 per cent ethanol, allowing reliable mucosal destruction with a 5
      min contact duration. CONCLUSION: Ninety-five per cent ethanol and STD after
      pretreatment with a mucosal exfoliant solution may be the combination of choice
      for in situ gallbladder mucosal ablation.

PMID- 9171751
TI  - Ultrasonographic investigation of the pathogenesis of infusion thrombophlebitis.
AB  - BACKGROUND: Thrombophlebitis frequently complicates intravenous infusion, but its
      precise pathogenesis remains unclear. METHODS: Serial B mode ultrasonographic
      imaging was used to detect intraluminal thrombosis when intravenous nutrition was
      delivered via fine-bore catheters inserted into peripheral veins. RESULTS:
      Thrombus was detected in 14 of 22 catheterized veins. There were nine episodes of
      clinical phlebitis; each was associated with intravenous thrombosis. Venospasm
      was not observed. The time at which thrombus was first detected varied from
      within 24 h to more than 15 days after catheterization. Detection of intravenous
      thrombosis within 24 h of catheter insertion was associated with early catheter
      complications. Early thrombus tended to be found close to the site of
      venepuncture, whereas late thrombus was found at the catheter tip, where the
      hypertonic feed was delivered. DISCUSSION: Ultrasonographic imaging was a useful
      technique for investigation of infusion thrombophlebitis. Two patterns of
      thrombosis were observed: distal early thrombosis and proximal late thrombosis.
      Information acquired may help in the design of novel catheters and strategies to
      reduce the incidence of thrombophlebitis.

PMID- 9171752
TI  - Prospective randomized trial of high-dose bolus versus low-dose tissue
      plasminogen activator infusion in the management of acute limb ischaemia.
      Thrombolysis Study Group.
AB  - INTRODUCTION: Accelerated thrombolysis with high-dose bolus tissue plasminogen
      activator (tPA) may enable patients with more severe acute leg ischaemia to be
      treated without recourse to surgery. This study was a randomized comparison of
      two thrombolytic regimens. METHODS: One hundred patients with acute leg ischaemia
      of less than 30 days' duration were randomized to receive either high-dose bolus
      tPA (three doses of 5 mg over 30 min, then 3.5 mg/h for up to 4 h, then 0.5-1.0
      mg/h) or conventional low-dose tPA (0.5-1.0 mg/h). The groups were well matched
      for age, cardiovascular risk factors, duration and severity of ischaemia, site,
      cause and length of arterial occlusion. RESULTS: The median duration of infusion
      in the high-dose group was 4.0 (range 0.25-46) h compared with 20 (range 2-46) h
      for low-dose infusion (P < 0.0001). Successful thrombolysis was achieved in 45 of
      49 high-dose and 39 of 44 low-dose infusions but significantly more adjunctive
      procedures were required following high-dose bolus infusion (26 versus 16
      patients) (P = 0.002). Thirty days after treatment was commenced, limb salvage
      was achieved in 39 of 49 patients in the high-dose group compared with 37 of 44
      who had a low-dose infusion of tPA. Six and two patients respectively required
      amputation. Four patients in the high-dose group and five in the low-dose group
      died. Three patients in each group suffered a major haemorrhage and one in the
      low-dose group had a stroke. CONCLUSION: High-dose bolus therapy significantly
      accelerated thrombolysis with tPA without compromising outcome. Some 50 per cent
      of patients were treated within 4 h enabling thrombolysis to be used as primary
      therapy for patients with acute critical ischaemia.

PMID- 9171753
TI  - Safe laparoscopic appendicectomy in suppurative appendicitis.

PMID- 9171754
TI  - Evaluation of a policy of total mesorectal excision for rectal and rectosigmoid
      cancers.
AB  - BACKGROUND: Total mesorectal excision (TME) is advocated for rectal cancer but
      the indications and extent of resection vary widely between surgeons. METHODS:
      Seventy-six consecutive patients (61 elective, 15 acute admission) with rectal or
      rectosigmoid cancer were admitted to a unit where TME was the preferred surgical
      option for potentially curative cancer at all levels of the rectum. RESULTS:
      Procedures undertaken were anterior resection (38 patients), abdominoperineal
      resection (18), Hartmann's procedure (ten) and transanal excision (one). Six
      patients had proximal faecal diversion alone and surgery was withheld in three.
      Anastomotic leaks occurred in six of 37 patients who had anterior resection with
      primary anastomosis, resulting in one early death. The presence of a proximal
      stoma did not influence the rate or seriousness of anastomotic dehiscence. After
      potentially curative TME in 45 patients, there have been eight local recurrences,
      four associated with systemic metastases and four which occurred in isolation
      (median follow-up 34 months). CONCLUSION: Curative TME was deemed appropriate in
      59 per cent of unselected patients with rectal cancer. It was associated with few
      local recurrences but a morbidity rate that questions its role in treatment of
      upper third tumours.

PMID- 9171755
TI  - Influence of hospital- and surgeon-related factors on outcome after treatment of
      rectal cancer with or without preoperative radiotherapy.
AB  - BACKGROUND: Preoperative radiotherapy reduces recurrence rates after surgery for
      rectal cancer but other variables may also affect outcome. The Stockholm Rectal
      Cancer Study Group has conducted two prospective randomized trials on
      preoperative radiotherapy in rectal cancer. METHODS: This study analysed
      postoperative morbidity and mortality, local recurrence rate and death from
      rectal cancer in 1399 patients, according to different hospital- and surgeon
      related factors. RESULTS: Patients operated on by surgeons who were certified
      specialists for at least 10 years had a lower risk of local recurrence (relative
      risk 0.8 (95 per cent confidence interval (c.i.) 0.6-1.0)) and death from rectal
      cancer (relative risk 0.8 (95 per cent c.i. 0.7-0.9)). The risk was also lower
      for patients operated on in university hospitals (relative risk of local
      recurrence 0.7 (95 per cent c.i. 0.5-0.9), relative risk of death from rectal
      cancer 0.8 (95 per cent c.i. 0.7-1.0)) compared with community hospitals,
      although the results in some community hospitals were similar to those in
      university hospitals. The proportional reduction of local recurrence rate after
      preoperative radiotherapy was not significantly different for the studied
      institutions and surgeons. CONCLUSION: There was a significant surgeon-related
      variation in patient outcome, which is probably related to the surgical
      technique. Although improved technique may reduce the local recurrence rate,
      preoperative radiotherapy is still beneficial concerning local control and
      survival.

PMID- 9171756
TI  - Mutant plasma p53 protein levels: prognostication in colorectal carcinoma.

PMID- 9171757
TI  - Use of an angled knife in rectal surgery.

PMID- 9171758
TI  - A prospective randomized study of follow-up after radical surgery for colorectal
      cancer.
AB  - BACKGROUND: The possible benefit for patients from follow-up examinations after
      curative surgery for colorectal cancer is unproven. The purpose of this study was
      to determine whether survival is improved by frequent follow-up examinations.
      METHODS: A total of 597 patients less than 76 years old treated with radical
      surgery for colorectal cancer were included in the study from 1983 to 1994.
      Patients were randomized to frequent follow-up (group 1) or virtually no follow
      up (group 2) with examinations at 5 and 10 years. RESULTS: Group 1 comprised 290
      patients, group 2 contained 307. Recurrence was equally frequent (26 per cent),
      but the time of diagnosis was 9 months earlier in group 1; also, more recurrences
      were asymptomatic in group 1 and more patients had new surgery with curative
      intent (P = 0.02). However, no improvement in overall survival or in cancer
      related survival resulted. CONCLUSION: Patients subjected to intensive follow-up
      have recurrence diagnosed earlier, and have more operations for recurrence, but
      the survival results suggest that any major improvement by intensive follow-up is
      unlikely.

PMID- 9171759
TI  - Intradermal methylene blue injection for the treatment of intractable idiopathic
      pruritus ani.

PMID- 9171760
TI  - Recognition of a pathological appendix during laparoscopy: a prospective study of
      81 cases.

PMID- 9171761
TI  - Management of ileosigmoid knotting.
AB  - BACKGROUND: Ileosigmoid knotting is a rare cause of intestinal obstruction.
      METHODS: The clinical records of 16 patients treated for ileosigmoid knotting
      were evaluated retrospectively. RESULTS: There were 11 men and five women. The
      mean age was 45 years. The mean duration of symptoms was 4.4 days. Plain
      abdominal radiographs showed multiple air-fluid levels in the colon and/or small
      bowel. At operation, ileum and/or sigmoid colon necrosis was observed in 13
      patients, both ileum and total colon necrosis in two, while there was no necrosis
      in one patient. Resection of necrotic bowel was necessary in 15 patients.
      Intestinal continuity was restored by primary anastomosis in 12; three required a
      stoma. The patient without necrosis was treated by detorsion and mesosigmoplasty.
      Three of 16 (19 per cent) patients died; septic shock was the major cause of
      death. CONCLUSION: Aggressive preoperative resuscitation, appropriate antibiotic
      therapy, effective surgery and postoperative metabolic support help minimize
      morbidity and mortality rates.

PMID- 9171762
TI  - Management of benign rectal stricture by implantation of a self-expanding
      prosthesis.

PMID- 9171763
TI  - Skin appendage involvement in anal intraepithelial neoplasia.
AB  - BACKGROUND: High-grade anal intraepithelial neoplasia (AIN III) may be
      premalignant. Surgical excision of large areas of anal epithelium carries
      significant morbidity. Ablation treatments may carry less morbidity; however, the
      depth of ablation is uncertain and failure to ablate dysplasia in hair shafts and
      other skin appendages may lead to early recurrence. METHODS: This study assesses
      morphometric aspects of skin appendages in perianal skin and anal canal mucosa in
      tissues from 30 patients with AIN III. Both normal and dysplastic epithelium was
      assessed in each patient. The depth to which AIN III involved skin appendages was
      measured using computerized image analysis. RESULTS: Both the perianal epidermis
      and anal canal mucosa affected by AIN III were significantly thicker than normal.
      Nineteen of 30 patients with AIN III had skin appendage involvement. Some 57 per
      cent of hair follicles (79 of 138), 16 per cent of sebaceous glands (11 of 69)
      and 25 per cent of sweat glands (24 of 96) observed beneath an abnormal
      epithelium had evidence of AIN. The median depth of AIN involvement of the hair
      follicle was 1.14 (range 0.44-1.67) mm, sebaceous glands 1.44 (range 0.96-1.90)
      mm, and sweat glands 0.94 (range 0.50-2.20) mm. These figures do not take into
      account tissue shrinkage due to histological processing. CONCLUSION: AIN III
      involvement of epithelial appendages is a significant problem. For disease
      eradication, tissue destruction or removal to a depth of at least 2.2 mm below
      the adjacent basement membrane is required. Surgical excision of high-grade AIN
      remains the treatment of choice.

PMID- 9171764
TI  - Comparison of three techniques for adrenalectomy.
AB  - BACKGROUND: Conventional open adrenal surgery requires relatively large incisions
      and is associated with postoperative wound pain, intercostal neuralgia and
      pulmonary complications. Introduction of laparoscopic techniques has enabled
      development of minimally invasive adrenalectomy. METHODS: A case-control study of
      nine open, nine transperitoneal laparoscopic and 12 retroperitoneal endoscopic
      adrenalectomies was done in patients who were matched for Quetelet index, adrenal
      disorder and size of adrenal lesion; all tumours were less than 6 cm in diameter.
      RESULTS: Conversion to open adrenalectomy was necessary in two patients having
      transperitoneal laparoscopic adrenalectomy and in one having retroperitoneal
      endoscopic adrenalectomy. Operative time was longest in transperitoneal
      laparoscopic adrenalectomy (P = 0.004 and P = 0.005 versus open and
      retroperitoneal endoscopic adrenalectomy respectively). Blood loss was least in
      retroperitoneal endoscopic adrenalectomy (P = 0.01 versus both other groups). End
      tidal carbon dioxide increase was greater in transperitoneal laparoscopic and
      retroperitoneal endoscopic than in open adrenalectomy (P = 0.014 and P = 0.01
      respectively). After retroperitoneal endoscopic adrenalectomy, use of analgesia
      was least (P = 0.0003 versus other groups). Postoperative hospital stay was
      shortest after retroperitoneal endoscopic adrenalectomy (P = 0.024 and P = 0.027
      versus open and transperitoneal laparoscopic procedures respectively).
      CONCLUSION: Retroperitoneal endoscopic adrenalectomy was optimal in patients with
      small adrenal tumours.

PMID- 9171765
TI  - Incidence of Meckel's diverticulum in Turkey.

PMID- 9171766
TI  - Herniography for groin pain of uncertain origin.

PMID- 9171767
TI  - Acute stomal 'contact' dermatitis or pemphigus.

PMID- 9171768
TI  - Effect of fundoplication on transient lower oesophageal sphincter relaxation and
      gas reflux.
AB  - BACKGROUND: Fundoplication is used widely to treat severe gastro-oesophageal
      reflux disease. Difficulty in belching and increased flatulence are common side
      effects. Transient lower oesophageal sphincter (LOS) relaxation is important to
      help vent gas from the stomach. The effect of fundoplication on LOS function and
      gas reflux was therefore investigated. METHODS: Oesophageal manometry was
      performed before operation and 3-15 months after fundoplication in 14 patients
      with reflux disease who had a total (360 degrees) fundoplication. Five patients
      also had highly selective vagotomy. Gastric distension was induced by 750 ml
      carbon dioxide. RESULTS: Fundoplication reduced the median number of episodes of
      gas reflux during 10 min of gastric distension from 5 (interquartile range
      (i.q.r.) 3-7) to 0 (i.q.r. 0), and the median number of transient LOS relaxations
      from 4 (i.q.r. 2-6) to 0 (i.q.r. 0-1). Fundoplication did not affect basal LOS
      pressure but significantly increased nadir pressure during swallow-induced
      relaxation. CONCLUSION: Fundoplication controls reflux by inhibiting the
      triggering of transient LOS relaxation and by preventing the complete ablation of
      pressure at the gastro-oesophageal junction during LOS relaxation. These effects
      may also contribute to the side-effects of the operation.

PMID- 9171769
TI  - Delay in treatment for oesophageal cancer.
AB  - BACKGROUND: Dysphagia is the cardinal symptom of oesophageal cancer, yet many
      patients present late. This study examined prospectively the interval between
      onset of dysphagia and treatment and identified reasons for delay. METHODS:
      Patients with histologically confirmed oesophageal carcinoma were questioned
      about duration of symptoms and about each step of their diagnostic work-up. Delay
      was estimated from date of onset of symptoms to definitive treatment. RESULTS:
      Median delay was 15 weeks for 78 patients with dysphagia, and 17 weeks for 22
      patients with other symptoms. The most frequent cause of delay was late
      presentation to the family doctor (44 per cent). For patients treated with
      surgery alone there was a trend towards more advanced stage of disease with
      longer delay to treatment, but no correlation with survival (P = 0.25).
      CONCLUSION: Lack of awareness of the sinister significance of dysphagia is the
      most important cause for delay in presentation of patients with oesophageal
      cancer.

PMID- 9171770
TI  - Button caecostomy in the management of faecal incontinence.

PMID- 9171771
TI  - One-wound laparoscopic cholecystectomy.

PMID- 9171772
TI  - Percutaneous transluminal angioplasty of the internal carotid artery.

PMID- 9171773
TI  - Laparoscopic appendicectomy.

PMID- 9171774
TI  - Prospective randomized trial comparing sequential avulsion with stripping of the
      long saphenous vein.

PMID- 9171775
TI  - Audit of general practitioner referrals to a surgical assessment unit: new
      methods to improve the efficiency of the acute surgical service.

PMID- 9171776
TI  - Rectus sheath bupivacaine analgesia after aortic surgery.

PMID- 9171777
TI  - Desmoids in familial adenomatous polyposis.

PMID- 9171778
TI  - Prospective randomized trial comparing postoperative pain and return to physical
      activity after transabdominal preperitoneal, total preperitoneal or Shouldice
      technique for inguinal hernia repair.

PMID- 9171779
TI  - Successful use of size-mismatched liver allografts in children by delayed primary
      closure of abdominal wall.

PMID- 9171780
TI  - Percutaneous transluminal angioplasty of the internal carotid artery.

PMID- 9171781
TI  - Randomized trial of periportal peritoneal bupivacaine for pain relief after
      laparoscopic cholecystectomy.

PMID- 9171782
TI  - Incidence and nature of bile duct injuries following laparoscopic
      cholecystectomy: an audit of 5913 cases.

PMID- 9171783
TI  - Colonic pouches in the treatment of low rectal cancer.

PMID- 9171784
TI  - Shunt insufficiency after transjugular intrahepatic portosystemic stent-shunt:
      the whens, whys, hows and what should we do about it?

PMID- 9171785
TI  - Small airways disease: expiratory computed tomography comes of age.

PMID- 9171786
TI  - Pictorial review: magnetic resonance imaging of acute orthopaedic trauma to the
      upper extremity.

PMID- 9171787
TI  - Non-invasive cholangio-pancreatography by breath-hold magnetic resonance imaging:
      preliminary results.
AB  - AIMS: A preliminary comparison of a prototype breath-hold magnetic resonance
      cholangio-pancreatography (MRCP) technique for non-invasive imaging of the
      pancreatic and biliary ducts with endoscopic retrograde cholangio-pancreatography
      (ERCP). METHOD: Twenty ERCP and MRCP examinations were performed in 19 patients
      referred for routine ERCP with suspected biliary or pancreatic abnormalities. The
      MRCP technique employed a modified heavily T2-weighted thick slice RARE sequence
      that allowed up to three images to be obtained in a 16 second breath-hold. The
      examinations were reported independently and the findings compared. RESULTS: MRCP
      accurately discriminated between patients without obstruction (n = 12) and those
      with (n = 8) and correctly diagnosed the cause of obstruction (three
      choledocholithiasis, five malignant stricture). In the 12 patients without
      obstruction the examinations were concordant in eight. In the remaining four
      patients MRCP provided more information than the corresponding ERCP study,
      diagnosing a pseudocyst in one patient and visualizing the entire pancreatic duct
      in three patients in whom this was not possible at ERCP. CONCLUSIONS: These
      preliminary results suggest that a breath-hold MRCP technique may allow the
      selection of those patients with obstructive lesions that require therapeutic
      ERCP intervention, and may have the potential to reduce the need for diagnostic
      ERCP examinations.

PMID- 9171788
TI  - Detectability and appearance of bile duct calculus on MR imaging of the abdomen
      using axial T1- and T2-weighted sequences.
AB  - This is a retrospective study with the objective of assessing the appearance and
      detectability of bile duct calculi on axial abdominal magnetic resonance imaging
      (MRI). Axial spin-echo (SE) T1-weighted and Turbo-spin-echo (TSE) T2-weighted
      images of the upper abdomen of 23 patients suffering from acute cholangitis with
      known bile duct calculi were retrospectively analysed. Bile duct calculi could be
      visualized on a T1-weighted SE sequence in 10 (47%) patients. T2-weighted TSE
      images identified bile duct calculi in 20 (87%) patients. On the T1-weighted
      sequence, eight out of 10 (80%) visualized common duct stones were slightly
      hyperintense compared to bile. On T2-weighted sequence, 27 out of 34 (79%)
      detectable common duct stones were uniformly hypointense compared to bile, but
      seven stones (21%) had mixed signal intensity.

PMID- 9171789
TI  - Late radiation change in the CNS: MR imaging following gadolinium enhancement.
AB  - Magnetic resonance imaging is the best imaging technique for the detection of
      radiotherapy-induced changes in the central nervous system but there are few
      studies detailing the MRI appearances of radiation effects following enhancement
      with intravenous gadolinium. In this paper, gadolinium enhanced MR imaging
      findings were reviewed in seven patients with evidence of late radiation injury
      following radiotherapy for primary head and neck tumours. On T1-weighted enhanced
      sequences, abnormal focal areas were present in the anterior temporal lobes and
      antero-inferior aspects of the frontal lobes. These lesions were well defined and
      enhanced intensely following intravenous gadolinium. They were present in the
      white matter in five patients and involved both grey and white matter in two
      patients. Cystic components were present in larger lesions in three patients and
      mass effect was present around the enhancing lesions in four patients. All
      abnormalities occurred within the radiation treatment portals and corresponded to
      the distribution of increased signal intensity changes in the brain on T2
      weighted images. Late radiation-induced injury should be considered in the
      differential diagnosis of any intensely enhancing lesion occurring within
      irradiated brain tissue.

PMID- 9171790
TI  - Magnetic resonance imaging of the shoulder: assessment of effectiveness.
AB  - OBJECTIVES: To quantify how magnetic resonance imaging (MRI) influences
      clinicians' diagnosis, diagnostic confidence and management plans in patients
      with shoulder problems. To investigate whether such changes are associated with
      an improvement in health. METHODS: A prospective observational study on all
      patients referred to a regional centre for MRI of the shoulder over a 6-month
      period. Data on diagnosis, diagnostic confidence and proposed management before
      MRI were compared with diagnoses and actual management after MRI. In addition,
      short form 36 item (SF-36) health survey data were collected at referral and
      again 6 months later. RESULTS: In 86 of 99 MRI referrals there was sufficient
      clinical data for the patient to enter the study. MRI led to previously
      unsuspected diagnoses in 20 of 59 patients where the clinicians had provided full
      diagnostic information before and after the examination. When MRI confirmed the
      clinical diagnosis, significant improvements in clinicians' diagnostic confidence
      were found (P < 0.001). MRI led to a change in management (P < 0.05) in 44 (62%)
      of the 71 patients where full management plans were available. Health survey
      results were available in 62 patients; although there were some improvements in
      SF-36 scores, these did not reach statistical significance. CONCLUSION: Magnetic
      resonance imaging of the shoulder significantly influences clinicians' diagnoses
      and management plans. However, patients do not record a statistically significant
      improvement in health-related quality of life over 6 months.

PMID- 9171791
TI  - Complete pre-operative imaging assessment of abdominal aortic aneurysm with
      spiral CT angiography.
AB  - PURPOSE: A prospective evaluation of spiral CT angiography (SCTA) as the sole pre
      operative imaging modality for abdominal aortic aneurysm repair. MATERIALS AND
      METHODS: Spiral CT angiography was compared with conventional transfemoral
      angiography in 30 patients and results correlated with surgical findings in 22
      patients. The following features were assessed: renal artery number and disease;
      upper and lower aneurysm extent; aneurysm size; perianeurysmal inflammation;
      iliac artery disease; radiation dose; and contrast usage. RESULTS: Spiral CT
      angiography agreed with conventional angiography in all cases of severe stenosis
      or occlusion of renal arteries and had 90% agreement overall for renal artery
      disease. Two of nine accessory renal arteries seen at conventional angiography
      were missed. For showing aneurysm extent SCTA was 100% sensitive, and performed
      better than conventional angiography. Aneurysm size was better shown with SCTA.
      In iliac disease SCTA, as performed in this study, was poor for mild-moderate
      disease, but detected four of six severely stenosed/occluded iliac arteries seen
      at conventional angiography. Prospective sensitivity for perianeurysmal
      inflammation was 33%. Radiation dose for SCTA was approximately twice and
      contrast dose approximately three times that for conventional angiography.
      CONCLUSION: Spiral CT angiography can provide all the necessary imaging
      information to plan aneurysm repair in the non-claudicant.

PMID- 9171792
TI  - Spontaneous intramural small bowel haemorrhage: importance of non-contrast CT.
AB  - The purpose of this study was to evaluate the abdominal CT findings in patients
      with spontaneous intramural small bowel haemorrhage. We retrospectively reviewed
      the abdominal CT scans of six patients with known intramural small bowel
      haemorrhage. All of the patients had an underlying coagulopathy. All six patients
      underwent CT examinations without oral or intravenous contrast media. All six non
      contrast CT scans showed hyperattenuation of the involved bowel segments, with
      thickened and dilated proximal small bowel. Therefore, patients who are
      clinically at risk for intramural small bowel haemorrhage should undergo a non
      contrast CT scan of the abdomen prior to the routine oral and intravenous
      contrast-enhanced scan. In most cases the non-contrast scan will provide
      definitive diagnostic information which may not be evident from the contrast
      enhanced scan alone.

PMID- 9171793
TI  - Computed tomographic evaluation of gastric emphysema--a report of three cases.
AB  - We present three patients, one male and two females, who had gastric emphysema
      demonstrated by computed tomography (CT) by chance. All patients had
      adenocarcinoma of the gastric antrum resulting in gastric outlet obstruction. We
      have classified these as the obstructive type of gastric emphysema. An additional
      cause in two of our patients could be a recent biopsy at UGI endoscopy. In one
      patient the emphysema was localized and the diagnosis could only have been made
      by CT. The two other patients had the usual pattern of extensive mural gas along
      the greater and lesser curvature of the stomach while dissection of gas into the
      retroperitoneum was present in one of them. There were no systemic effects
      attributable to the emphysema in all three patients. This reinforces the belief
      that gastric emphysema is not infective in origin.

PMID- 9171794
TI  - Budd-Chiari syndrome resulting from intrahepatic IVC compression secondary to
      blunt hepatic trauma.
AB  - Hepatic venous outflow obstruction (Budd-Chiari syndrome)is a rare sequel of
      abdominal trauma. Three cases of Budd-Chiari syndrome resulting from obstruction
      to the intrahepatic IVC by liver injury are reported. The CT findings include
      extrinsic compression of the intrahepatic inferior vena cava (IVC) by
      intraparenchymal and/or subcapsular hepatic haematoma, non-visualization or
      narrowing of one or more main hepatic veins with intravenous contrast-enhanced
      CT, and accumulation of low attenuation ascites. This entity should be
      distinguished from intraperitoneal bile leak or hemoperitoneum associated with
      major liver injury with which it could be confused. Decompression of the IVC and
      hepatic veins by surgical or percutaneous drainage of intrahepatic or subcapsular
      hematoma was curative in two of the three patients.

PMID- 9171796
TI  - Case report: focal amyloidosis of the maxillary antrum: plain film, CT and MR
      appearances.

PMID- 9171795
TI  - Technical report: coaxial catheter: a new technique for sequential spiral CT
      during arterial portography and hepatic arteriography.
AB  - PURPOSE: To evaluate a coaxial catheter method to sequentially acquire spiral
      computed tomography (CT) during arterial portography (CTAP) and hepatic
      arteriography (CTA) at a single transfer. PATIENTS AND METHODS: Sixteen patients
      with malignant hepatic tumours (12 patients with hepatocellular carcinoma, four
      with metastases) were studied using spiral CT. Depending upon the vascular
      anatomy revealed by conventional coeliac and superior mesenteric arteriography,
      an outer and inner catheter were selectively placed to perform CTA and CTAP,
      respectively. CTAP images were obtained first, while injecting contrast material
      through an inner catheter followed by the acquisition of the CTA images during
      injection through an outer catheter. In three patients, the resected specimens
      were available for comparison with the imaging findings. RESULTS: In 12 patients
      with standard hepatic arterial anatomy, high quality images of CTAP and CTA were
      obtained. More lesions were detected by the combination of CTAP and CTA than by
      CTAP or CTA alone in five patients. In one patient with breast carcinoma and a
      left hepatic artery arising from the left gastric artery, numerous hepatic
      metastases were delineated on both sets of images. In three patients with
      replaced or accessory right hepatic arteries, evaluation of the whole liver was
      difficult on CTA. These procedures were well tolerated by all 16 patients and no
      complication or technical failure was experienced. CONCLUSION: These preliminary
      data support this new technique as a promising method of performing CTA and CTAP
      in patients with standard hepatic arterial anatomy with a single catheter
      insertion.

PMID- 9171797
TI  - Case report: MR appearances in vitamin B12 neuropathy.

PMID- 9171798
TI  - Case report: venous sinus thrombosis: the use of thrombolysis.

PMID- 9171799
TI  - Case report: focal fatty infiltration of the liver with accumulation defect on Tc
      99m colloid and Tc-99m-GSA scintigraphy.

PMID- 9171800
TI  - MRI of Klippel-Trenaunay syndrome: use of the Short Tau Inversion Recovery (STIR)
      sequence.

PMID- 9171801
TI  - Transrectal ultrasound in the diagnosis of prostate carcinoma.

PMID- 9171802
TI  - Intravascular injection of iodinated contrast media.

PMID- 9171803
TI  - [Alzheimer dementia. Main goal: improve quality of life for patients and family].

PMID- 9171804
TI  - Temperament and substance abuse in schizophrenia: is there a relationship?
AB  - The influence of temperament on substance abuse in schizophrenia is poorly
      understood, whereas it is known to play an important role in other clinical
      populations. In a sample of 28 male schizophrenics, Cloninger's dimensions of
      temperament were measured with the use of the Tridimensional Personality
      Questionnaire (TPQ). Levels of four commonly used substances were recorded. There
      was a significant correlation between the novelty-seeking dimension and past use
      of alcohol, cannabis, and caffeine and current use of caffeine and nicotine.
      There was no relationship between substance use and clinical symptoms or
      demographic variables. The possible implications of abnormal mean TPQ scores in
      the sample as well as a weak correlation between symptom patterns and TPQ scores
      are discussed. The findings suggest that novelty-seeking type behaviors
      contribute to substance use in schizophrenia.

PMID- 9171805
TI  - Sedative use disorders in opiate-dependent patients: association with psychiatric
      and other substance use disorders.
AB  - Opiate-dependent patients (N = 231), classified by sedative disorder status, were
      characterized according to DSM-IIIR on substance use and psychiatric disorders.
      Twenty-one percent currently (CUR+) had sedative use disorder, 39% had a history
      (HX+) of sedative use disorder, and 40% had no history (HX-) of this disorder.
      Several group differences were found. The HX+ and CUR+ groups had more lifetime
      drug use disorders (means = 4.5 and 4.3 vs. 3.2 in the HX- group), including
      alcohol, cannabis, stimulants, cocaine, and hallucinogens. In contrast, other
      psychiatric disorders (e.g., anxiety and depression) were low in prevalence and
      did not differ across groups, with the exception of a higher prevalence of
      antisocial personality disorder in the HX+ and CUR+ groups (39.6% and 38.5% vs.
      17.9% in HX- group). The results suggest that sedative use disorder is related
      more to a severe spectrum of multiple substance abuse than it is to self
      medication of underlying mood or anxiety disorders.

PMID- 9171806
TI  - Integrated treatment for dually diagnosed homeless adults.
AB  - This study examined the effects of integrating mental health, substance abuse,
      and housing interventions for homeless persons with co-occurring severe mental
      illness and substance use disorder. With the use of a quasi-experimental design,
      integrated treatment was compared with standard treatment for 217 homeless,
      dually diagnosed adults over an 18-month period. The integrated treatment group
      had fewer institutional days and more days in stable housing, made more progress
      toward recovery from substance abuse, and showed greater improvement of alcohol
      use disorders than the standard treatment group. Abuse of drugs other than
      alcohol (primarily cocaine) improved similarly for both groups. Secondary
      outcomes, such as psychiatric symptoms, functional status, and quality of life,
      also improved for both groups, with minimal group differences favoring integrated
      treatment.

PMID- 9171807
TI  - Effectiveness of node-link mapping enhanced counseling for opiate addicts: a 12
      month posttreatment follow-up.
AB  - Drug abuse counseling was enhanced by node-link mapping, a visual representation
      technique, and evaluated in a posttreatment follow-up study. Clients randomly
      assigned to receive mapping counseling reported less criminal activity 12 months
      after treatment than did clients in the standard counseling condition. It was
      also found that among clients staying less than 6 months in treatment, those in
      the mapping group had fewer urine samples that tested positive for opiates at
      follow-up. Thus, mapping-enhanced counseling may be especially beneficial for
      clients who leave treatment prematurely.

PMID- 9171808
TI  - An investigation of worry content among generally anxious individuals.
AB  - The hypothesis of a distinctive content pattern of worry in generalized anxiety
      disorder (GAD) was investigated with the use of content categorization of GAD
      versus nonanxious control worries from both clinical and analogue samples. The
      GAD groups reported significantly more worry topics than the control groups. Some
      similarity in content patterns emerged across groups, with the most frequent
      content category for all groups involving family/interpersonal issues. However, a
      significant difference in the pattern of relative frequencies across groups was
      found: GAD was characterized by equally high relative frequencies for
      miscellaneous and work/school worries, whereas control groups had higher relative
      frequencies for work/school concerns and lower relative frequencies for
      miscellaneous worries. The miscellaneous worries of GAD individuals were
      particularly characterized by worry about minor/routine issues. These findings
      support DSM-IV descriptions of GAD as involving pervasive worry that includes
      worry about minor things.

PMID- 9171809
TI  - The religious needs and resources of psychiatric inpatients.
AB  - A recent survey of psychiatric research indicates religion has been given little
      attention, and when it has been considered, the measures have been simplistic.
      The present study was designed to describe the religious needs and resources of
      psychiatric inpatients. With the use of a multidimensional conception of religion
      and two established instruments, 51 adult psychiatric inpatients were surveyed
      about their religious needs and resources. For comparison, 50 general
      medical/surgical patients, matched for age and gender, were also surveyed. Eighty
      eight percent of the psychiatric patients reported three or more current
      religious needs. Although there were no differences in religious needs between
      the two patient groups, there were significant differences in religious
      resources. Psychiatric patients had lower spiritual well-being scores and were
      less likely to have talked with their clergy. Religion is important for the
      psychiatric patients, but they may need assistance to find resources to address
      their religious needs.

PMID- 9171810
TI  - The near-death experience as a focus of clinical attention.
AB  - Near-death experiences (NDEs) often produce profound changes in attitudes and
      behavior that can lead to psychosocial and psychospiritual problems. The
      diagnostic label of religious or spiritual problem, included in DSM-IV under the
      category of other conditions that may be a focus of clinical attention, was
      originally proposed to encompass NDEs and their aftereffects. Four cases are
      discussed in which patients presented with NDE-related problems, and differential
      diagnosis and current treatment strategies are reviewed. The inclusion of this
      new diagnostic category in the DSM-IV permits differentiation of NDEs and similar
      experiences from mental disorders and may lead to research into more effective
      treatment strategies.

PMID- 9171812
TI  - Posttraumatic reactions of hostages after an aircraft hijacking.

PMID- 9171811
TI  - Familial aggregation of DSM-IV alcohol use disorders: examination of the primary
      secondary distinction in a general population sample.
AB  - This study examined the familial aggregation of alcoholism in subgroups of
      respondents classified with respect to the primary-secondary distinction as it is
      related to DSM-IV major depression and alcohol use disorders. Rates of alcoholism
      among specific first- and second-degree relatives of male and female probands
      with primary, secondary, and concurrent depression (i.e., the comorbid groups)
      and with major depression only were compared with one another and with a normal
      control group. The results of this general population survey that uses a large
      representative sample of the U.S. were at variance with some findings from the
      clinical literature with regard to familial aggregation. Greater rates of
      alcoholism were found among first- and second-degree relatives of the major
      depression only group compared with normal controls. Male and female probands of
      all three comorbid groups were not shown to convey a greater risk of alcoholism
      to their offspring compared with the normal control group or the major depression
      only group. The discrepancy between clinical research findings and those of this
      general population study were discussed in terms of methodological
      considerations.

PMID- 9171813
TI  - Psychological distress and intrusive thoughts in cancer patients.

PMID- 9171814
TI  - Remission of self-mutilation in a patient with borderline personality during
      risperidone therapy.

PMID- 9171815
TI  - Correlation of testosterone with aggression in demented elderly men.

PMID- 9171816
TI  - Up the function.

PMID- 9171817
TI  - Of men in mice.

PMID- 9171818
TI  - Two uses for old SOX.

PMID- 9171819
TI  - Repeat expansion--all in a flap?

PMID- 9171820
TI  - Right and left go dHAND and eHAND.

PMID- 9171821
TI  - BRCA1 is localized in cytoplasmic tube-like invaginations in the nucleus.

PMID- 9171822
TI  - Congenital hypothyroidism caused by a mutation in the Na+/I- symporter.

PMID- 9171823
TI  - A new dimension for the human genome project: towards comprehensive expression
      maps.
AB  - The current Human Genome Project is largely devoted to structural
      characterisation of our genome. We now need international co-ordination of a
      second phase of genome analysis, the systematic construction of expression maps
      using both basic and high-resolution expression assays. Databases recording
      different types of expression pattern for a variety of human cell types need to
      be established and co-ordinated. There is a compelling need for a database of
      gene expression in early human development, but the scarcity of human material
      for study requires optimisation of research strategies and co-ordination of
      expression studies in early human and mouse development.

PMID- 9171824
TI  - Functional expression and germline transmission of a human chromosome fragment in
      chimaeric mice.
AB  - Human chromosomes or chromosome fragments derived from normal fibroblasts were
      introduced into mouse embryonic stem (ES) cells via microcell-mediated chromosome
      transfer (MMCT) and viable chimaeric mice were produced from them. Transferred
      chromosomes were stably retained, and human genes, including immunoglobulin (Ig)
      kappa, heavy, lambda genes, were expressed in proper tissue-specific manner in
      adult chimaeric tissues. In the case of a human chromosome (hChr.) 2-derived
      fragment, it was found to be transmitted to the offspring through the germline.
      Our study demonstrates that MMCT allows for introduction of very large amounts of
      foreign genetic material into mice. This novel procedure will facilitate the
      functional analyses of human genomes in vivo.

PMID- 9171825
TI  - A functional neo-centromere formed through activation of a latent human
      centromere and consisting of non-alpha-satellite DNA.
AB  - We recently described a human marker chromosome containing a functional neo
      centromere that binds anti-centromere antibodies, but is devoid of centromeric
      alpha-satellite repeats and derived from a hitherto non-centromeric region of
      chromosome 10q25. Chromosome walking using cloned single-copy DNA from this
      region enabled us to identify the antibody-binding domain of this centromere.
      Extensive restriction mapping indicates that this domain has an identical genomic
      organization to the corresponding normal chromosomal region, suggesting a
      mechanism for the origin of this centromere through the activation of a latent
      centromere that exists within 10q25.

PMID- 9171826
TI  - Regulation of cardiac mesodermal and neural crest development by the bHLH
      transcription factor, dHAND.
AB  - dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors
      that are expressed in mesodermal and neural crest-derived structures of the
      developing heart. In contrast to their homogeneous expression during avian
      cardiogenesis, during mouse heart development we show that dHAND and eHAND are
      expressed in a complementary fashion and are restricted to segments of the heart
      tube fated to form the right and left ventricles, respectively. dHAND and eHAND
      represent the earliest cardiac chamber-specific transcription factors yet
      identified. Targeted gene deletion of dHAND in mouse embryos resulted in
      embryonic lethality at embryonic day 10.5 from heart failure. Our description of
      the cardiac phenotype of dHAND mutant embryos is the first demonstration of a
      single gene controlling the formation of the mesodermally derived right ventricle
      and the neural crest-derived aortic arches and reveals a novel cardiogenic
      subprogramme for right ventricular development.

PMID- 9171827
TI  - The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type
      inflammation.
AB  - Structural alterations of the promoter region of the BCL-6 proto-oncogene
      represent the most frequent genetic alteration associated with non-Hodgkin
      lymphoma, a malignancy often deriving from germinal-centre B cells. The BCL-6
      gene encodes a zinc-finger transcriptional repressor normally expressed in both B
      cells and CD4+ T cells within germinal centres, but its precise function is
      unknown. We show that mice deficient in BCL-6 displayed normal B-cell, T-cell and
      lymphoid-organ development but have a selective defect in T-cell-dependent
      antibody responses. This defect included a complete lack of affinity maturation
      and was due to the inability of follicular B cells to proliferate and form
      germinal centres. In addition, BCL-6-deficient mice developed an inflammatory
      response in multiple organs characterized by infiltrations of eosinophils and IgE
      bearing B lymphocytes typical of a Th2-mediated hyperimmune response. Thus, BCL-6
      functions as a transcriptional switch that controls germinal centre formation and
      may also modulate specific T-cell-mediated responses. Altered expression of BCL-6
      in lymphoma represents a deregulation of the pathway normally leading to B cell
      proliferation and germinal centre formation.

PMID- 9171828
TI  - An imprinting element from the mouse H19 locus functions as a silencer in
      Drosophila.
AB  - Genomic imprinting as originally described in Sciara is displayed by many
      organisms. In mammals, X-inactivation and the parent-of-origin-specific silencing
      of imprinted genes are examples of this phenomenon. A heritable chromatin
      structural modification may be the critical mechanism in such instances of
      chromosome condensation and preferential gene inactivation. H19 is an imprinted
      gene in which the repressed paternal allele is hypermethylated and the compacted
      chromatin is relatively resistant to digestion by nucleases. In order to uncover
      underlying conserved epigenetic mechanisms we have introduced a mouse H19
      transgene into Drosophila. We show here that a 1.2-kb H19 upstream sequence
      functions in cis as a parent-of-origin independent silencing element in
      Drosophila. Strikingly, this cis-acting element is located within an upstream
      region that is necessary for H19 imprinting in mice. These results suggest
      involvement of an evolutionary conserved mechanism in both genes silencing in
      Drosophila and imprinting in mice.

PMID- 9171829
TI  - SOX9 directly regulates the type-II collagen gene.
AB  - Mutations in human SOX9 are associated with campomelic dysplasia (CD),
      characterised by skeletal malformation and XY sex reversal. During chondrogenesis
      in the mouse, Sox9 is co-expressed with Col2a1, the gene encoding type-II
      collagen, the major cartilage matrix protein. Col2a1 is therefore a candidate
      regulatory target of SOX9. Regulatory sequences required for chondrocyte-specific
      expression of the type-II collagen gene have been localized to conserved
      sequences in the first intron in rats, mice and humans. We show here that SOX9
      protein binds specifically to sequences in the first intron of human COL2A1.
      Mutation of these sequences abolishes SOX9 binding and chondrocyte-specific
      expression of a COL2A1-driven reporter gene (COL2A1-lacZ) in transgenic mice.
      Furthermore, ectopic expression of Sox9 trans-activates both a COL2A1-driven
      reporter gene and the endogenous Col2a1 gene in transgenic mice. These results
      demonstrate that COL2A1 expression is directly regulated by SOX9 protein in vivo
      and implicate abnormal regulation of COL2A1 during, chondrogenesis as a cause of
      the skeletal abnormalities associated with campomelic dysplasia.

PMID- 9171830
TI  - PKD1 interacts with PKD2 through a probable coiled-coil domain.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) describes a group of at
      least three genetically distinct disorders with almost identical clinical
      features that collectively affects 1:1,000 of the population. Affected
      individuals typically develop large cystic kidneys and approximately one half
      develop end-stage renal disease by their seventh decade. It has been suggested
      that the diseases result from defects in interactive factors involved in a common
      pathway. The recent discovery of the genes for the two most common forms of ADPKD
      has provided an opportunity to test this hypothesis. We describe a previously
      unrecognized coiled-coil domain within the C terminus of the PKD1 gene product,
      polycystin, and demonstrate that it binds specifically to the C terminus of PKD2.
      Homotypic interactions involving the C terminus of each are also demonstrated. We
      show that naturally occurring pathogenic mutations of PKD1 and PKD2 disrupt their
      associations. We have characterized the structural basis of their heterotypic
      interactions by deletional and site-specific mutagenesis. Our data suggest that
      PKD1 and PKD2 associate physically in vivo and may be partners of a common
      signalling cascade involved in tubular morphogenesis.

PMID- 9171831
TI  - Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal
      dystrophy.
AB  - The intermediate filament cytoskeleton of corneal epithelial cells is composed of
      cornea-specific keratins K3 and K12 (refs 1,2). Meesmann's corneal dystrophy
      (MCD) is an autosomal dominant disorder causing fragility of the anterior corneal
      epithelium, where K3 and K12 are specifically expressed. We postulated that
      dominant-negative mutations in these keratins might be the cause of MCD. K3 was
      mapped to the type-II keratin gene cluster on 12q; and K12 to the type-I keratin
      cluster on 17q using radiation hybrids. We obtained linkage to the K12 locus in
      Meesmann's original German kindred (Zmax = 7.53; theta = 0) and we also showed
      that the phenotype segregated with either the K12 or the K3 locus in two Northern
      Irish pedigrees. Heterozygous missense mutations in K3 (E509K) and in K12 (V143L;
      R135T) completely co-segregated with MCD in the families and were not found in
      100 normal unrelated chromosomes. All mutations occur in the highly conserved
      keratin helix boundary motifs, where dominant mutations in other keratins have
      been found to severely compromise cytoskeletal function, leading to keratinocyte
      fragility phenotypes. Our results demonstrate for the first time the molecular
      basis of Meesmann's corneal dystrophy.

PMID- 9171832
TI  - Mutations in the myosin VIIA gene cause non-syndromic recessive deafness.
AB  - Genetic hearing impairment affects around 1 in every 2,000 births. The bulk
      (approximately 70%) of genetic deafness is non-syndromic, in which hearing
      impairment is not associated with any other abnormalities. Over 25 loci involved
      in non-syndromic deafness have been mapped and mutations in connexin 26 have been
      identified as a cause of non-sydromic deafness. One locus for non-syndromic
      recessive deafness, DFNB2 (ref. 4), has been localized to the same chromosomal
      region, 11q14, as one of the loci, USH1B, underlying the recessive deaf-blind
      syndrome. Usher syndrome type 1b, which is characterized by profound congenital
      sensorineural deafness, constant vestibular dysfunction and prepubertal onset of
      retinitis pigmentosa. Recently, it has been shown that a gene encoding an
      unconventional myosin, myosin VIIA, underlies the mouse recessive deafness
      mutation, shaker-1 (ref. 5) as well as Usher syndrome type 1b. Mice with shaker-1
      demonstrate typical neuroepithelial defects manifested by hearing loss and
      vestibular dysfunction but no retinal pathology. Differences in retinal patterns
      of expression may account for the variance in phenotype between shaker-1 mice and
      Usher type 1 syndrome. Nevertheless, the expression of MYO7A in the
      neuroepithelium suggests that it should be considered a candidate for non
      syndromic deafness in the human population. By screening families with non
      syndromic deafness from China, we have identified two families carrying MYO7A
      mutations.

PMID- 9171833
TI  - The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are
      allelic defects of the myosin-VIIA gene.
AB  - Hereditary non-syndromic profound deafness affects about 1 in 2000 children prior
      to language acquisition. In 80% of the cases, the mode of transmission is
      autosomal recessive. The number of genes involved in these recessive forms of
      isolated deafness (DFNB genes) has been estimated to between 30 and 100. So far,
      ten DFNB genes have been mapped to human chromosomes, one of which has been
      isolated. By linkage analysis of a single family whose members were affected with
      profound deafness, some of them presenting with vestibular dysfunction, DFNB2 has
      been mapped to chromosome 11q13 (ref. 3). The gene responsible for a form of
      Usher syndrome type I, USH1B, has been assigned to the same chromosomal region.
      Usher syndrome associates profound congenital deafness and vestibular dysfunction
      with retinitis pigmentosa. In the homologous murine region are located the shaker
      1 mutations responsible for deafness and vestibular dysfunction. It has been
      demonstrated that the murine shaker-1 and human USH1B phenotypes result from
      mutations in the gene encoding myosin-VIIA. Based on mapping data as well as on
      the similarities between the phenotypes of DFNB2-affected patients and shaker-1
      mouse mutants, we have proposed that a defective myosin-VIIA may also be
      responsible for DFNB2 (ref. 1). Sequence analysis of each of the coding exons of
      the myosin-VIIA gene (MYO7A) was thus undertaken in the DFNB2-affected family. In
      the last nucleotide of exon 15, a G to A transition was detected, a type of
      mutation that is known to decrease the efficiency of splicing. Accordingly, this
      result shows that different mutations in MYO7A result in either an isolated or a
      syndromic form of deafness.

PMID- 9171834
TI  - Localization of genes controlling resistance to trypanosomiasis in mice.
AB  - Tsetse fly-transmitted trypanosomes (Trypanosoma spp.) cause "sleeping sickness'
      in man and have a serious impact on livestock-based agriculture in large areas of
      Africa. Multigene control of variation in susceptibility to trypanosomiasis is
      known to occur in mice, where the C57BI/6 (B6) strain is relatively resistant and
      the A/J (A) and Balb/c (B) strains are susceptible. Such resistance is also well
      described among several types of west African cattle. We report here the results
      of genome-wide scans for genes controlling this trait in the B6 mouse using
      crosses with two different susceptible strains. Regions on mouse chromosomes 5
      and 17 were found to be important in determining resistance in both crosses while
      an additional region on chromosome 1 showed evidence of involvement in only one
      cross. We confirmed the size of the effect due to chromosome 17 in F3 intercross
      populations fixed for alternative parental chromosomes. The three loci are of
      large effect and account for most of the genetic variation in both F2
      populations. We propose that they be designated Tir1, Tir2 and Tir3.

PMID- 9171835
TI  - Quantitative trait loci for cellular defects in glucose and fatty acid metabolism
      in hypertensive rats.
AB  - Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity
      are major causes of ill health in industrial societies. Disturbances of
      carbohydrate and lipid metabolism are a common feature of these disorders. The
      bases for these disturbances and their roles in disease pathogenesis are poorly
      understood. The spontaneously hypertensive rat (SHR), a widely used animal model
      of essential hypertension, has a global defect in insulin action on glucose
      metabolism and shows reduced catecholamine action on lipolysis in fat cells. In
      our study we used cellular defects in carbohydrate and lipid metabolism to
      dissect the genetics of defective insulin and catecholamine action in the SHR
      strain. In a genome screen for loci linked to insulin and catecholamine action,
      we identified two quantitative trait loci (QTLs) for defective insulin action, on
      chromosome 4 and 12. We found that the major (and perhaps only) genetic
      determinant of defective control of lipolysis in SHR maps to the same region of
      chromosome 4. These linkage results were ascertained in at least two independent
      crosses. As the SHR strain manifests many of the defining features of human
      metabolic Syndrome X, in which hypertension associates with insulin resistance,
      dyslipidaemia and abdominal obesity, the identification of genes for defective
      insulin and catecholamine action in SHR may facilitate gene identification in
      this syndrome and in related human conditions, such as type-2 diabetes and
      familial combined hyperlipidaemia.

PMID- 9171837
TI  - The place of "the tropics' in Western medical ideas since 1750.
AB  - The idea of "the tropics' as a region distinct from the "temperate' world has a
      long history and derives from European expansion and environmental theories
      especially from about 1750 onwards. Although the tropics were ascribed some
      positive attributes, the dominant concept was a negative one and the idea of
      distinctive tropical disease and the corresponding need for a separate specialty
      of tropical medicine largely grew out of this.

PMID- 9171836
TI  - Multilocus linkage of familial hyperkalaemia and hypertension,
      pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21.
AB  - Essential hypertension is a common multifactorial trait. The molecular basis of a
      number of rare diseases that after blood pressure in humans has been established,
      identifying pathways that may be involved in more common forms of hypertension.
      Pseudohypoaldosteronism type II (PHAII, also known as familial hyperkalaemia and
      hypertension or Gordon's syndrome; OMIM #145260), is characterized by
      hyperkalaemia despite normal renal glomerular filtration, hypertension and
      correction of physiologic abnormalities by thiazide diuretics. Mild
      hyperchloremia, metabolic acidosis and suppressed plasma renin activity are
      variable associated findings. The pathogenesis of PHAII is unknown, although
      clinical studies indicate an abnormality in renal ion transport. As thiazide
      diuretics are among the most efficacious agents in the treatment of essential
      hypertension, understanding the pathogenesis of PHAII may be of relevance to more
      common forms of hypertension. Analysis of linkage in eight PHAII families showing
      autosomal dominant transmission demonstrates locus heterogeneity of this trait,
      with a multilocus lod score of 8.1 for linkage of PHAII to chromosomes 1q31-q42
      and 17p11-q21. Interestingly, the chromosome-17 locus overlaps a syntenic
      interval in rat that contains a blood pressure quantitative trait locus (QTL).
      Our findings provide a first step toward identification of the molecular basis of
      PHAII.

PMID- 9171838
TI  - Spectrum of neuropsychiatric complications in 791 cases of typhoid fever.
AB  - Over a 6-year period, we studied 791 patients with multidrug-resistant typhoid
      fever, of whom 665 individuals (84%) developed neuropsychiatric manifestations.
      These were: acute confusional state (73%); myelitis (6%); cerebellitis (1%);
      parkinsonism (1%); acute psychosis (0.6%); meningo-encephalitis (0.5%);
      encephalitis (0.25%); sensory motor polyneuropathy, polymyositis, acute
      schizophrenia and bizarre neurological syndromes (0.12% each). Severe
      parkinsonian rigidity and meningo-encephalitis are associated with significant
      morbidity but very low mortality (0.5%).

PMID- 9171840
TI  - The role of low level Plasmodium falciparum parasitaemia in anaemia among infants
      living in an area of intense and perennial transmission.
AB  - Children under one year of age in an area of intense and perennial Plasmodium
      falciparum transmission were followed up for one year to establish to what extent
      chronic, low parasitaemia was associated with severe anaemia. There was a
      significant increase in the prevalence of anaemia (PCV < or = 25%) with increase
      in parasite density. PCV levels were related not only to concurrent parasite
      density but also decreased with densities measured one month previously. At any
      point in time, the mean PCV level in infants with low parasitaemia (< 1000
      parasites/microliter) was higher than that of infants with intermediate (1000
      9999/microliter) and high parasite densities (> or 10000/microliter). After the
      age of 7 months, infants with low parasite densities tend to recover, probably as
      a result of developing immunity. At the age of 12 months, they have similar PCV
      levels to infants with no detectable parasitaemia by microscopy. The maintenance
      of low parasite density appears crucial to the survival of infants in malaria
      endemic areas. The findings suggest that interventions which lower parasite
      densities in areas of intense transmission reduce the development of severe
      malarial anaemia and thus malaria-related mortality and morbidity in infants.

PMID- 9171839
TI  - Responses of multidrug-resistant Plasmodium falciparum parasites to mefloquine in
      Nigerian children.
AB  - Thirty-three children aged 6 months to 7 years from an area with multidrug
      resistant Plasmodium falciparum strains were treated with 25 mg/kg body weight of
      mefloquine base as a single oral dose. They were followed-up using the modified
      28-day WHO extended field test. The parasite isolates from these patients were
      cultured in vitro with different concentrations of mefloquine. All children were
      parasite-negative by day 4, and 31 remained so throughout the period of
      observation. Two patients who were parasitaemic on days 16 and 28 were
      successfully treated with a sulphadoxine/pyrimethamine combination.
      Parasitological and clinical responses were well correlated. The mean parasite
      clearance time was 65 +/- 10.2 hours. A mefloquine concentration of 64 pmol/well
      inhibited schizont growth and the EC50 and EC99 were 5.5 and 5.4 pmol/well (1.1
      and 10.8 mumol/l blood) respectively. This indicates reduced parasite
      susceptibility to the drug in vitro.

PMID- 9171841
TI  - Farm land size and onchocerciasis status of peasant farmers in south-western
      Nigeria.
AB  - Concern is being raised about the economic impact of the non-blinding strain of
      onchocerciasis, since half of those affected with onchocerciasis in Africa live
      in the forest zones where the non-blinding form is prevalent. WHO's TDR programme
      has embarked on multi-country studies on the social and economic effects of
      onchocercal skin disease (OSD). Baseline data from one site, the Ibarapa Local
      Government Area of Oyo State, Nigeria, is presented here. Farmers were screened
      for signs and symptoms of onchocerciasis including palpable nodules, reactive
      skin lesions and self-reported severe itching. Those having two or more of these
      conditions were classified as having severe OSD. A matching group of farmers
      without any of the signs or symptoms formed a control group. Women in the area
      either did not farm or held only one small plot. Land size comparisons were
      undertaken with 51 pairs of male farmers matched for age and location within 23
      small hamlets bordering the Ogun River. Farmers with OSD had significantly less
      farmland under cultivation (9117 m2) than those with no OSD (13850 m2). The
      farmers with OSD did not appear to have alternative income strategies to
      compensate and, consequently, they had a lower value of personal wealth
      indicators (e.g. iron sheet roofing, motorcycle) than those without OSD. One can
      conclude that although the effect of forest strain onchocerciasis is less
      dramatic than of the blinding from, the disease poses an important economic
      threat in the region.

PMID- 9171842
TI  - Infectivity of Cryptosporidium parvum oocysts is retained upon intestinal passage
      through a migratory water-fowl species (Canada goose, Branta canadensis).
AB  - Five Cryptosporidium-free Canada geese (Branta canadensis) were individually
      orally dosed with 3.5 x 10(6) Cryptosporidium parvum oocysts infectious to
      neonatal BALB/c mice. After intestinal passage, inoculum-derived oocysts
      extracted from goose faeces established severe infection in 14 neonatal BALB/c
      mice (inoculum dose 2.5 x 10(5)/mouse). The inoculum-derived oocysts were
      detected in goose faeces up to 9 days post-inoculation (PI); the number of intact
      oocysts and oocyst shells shed during the first 3 days PI was significantly
      higher than for the remaining 6 days PI (P < 0.01). Based on acid-fast stained
      air-dried direct wet smears, 62% of the oocysts in goose faeces were intact
      (oocyst shells) constituted 38%) and conformed to morphological features of
      viable and infectious inoculum oocysts. The fluorescence scores of the inoculated
      oocysts, obtained by use of the MERIFLUOR test, were identical to those obtained
      for the faeces-recovered oocysts (majority 3+ to 4+). The dynamics of oocyst
      shedding showed that overall, the birds released a significantly higher number of
      intact oocysts than oocyst (P < 0.01). Retention of the viability and infectivity
      of C. parvum oocysts following intestinal passage through a migratory water-fowl
      species has serious epidemiological implications. Water-fowl can serve as
      mechanical vectors for the water-borne oocysts and can contaminate surface waters
      with C. parvum. As the concentration of Cryptosporidium oocysts in source waters
      is attributable to water-shed management practices, water-shed protection
      programme officials should consider water-fowl as a potential factor enhancing
      contamination of the source water with Cryptosporidium.

PMID- 9171843
TI  - Assessment of vector microfilarial uptake as a comparatively non-invasive
      technique for monitoring onchocerciasis treatment campaigns in the Americas.
AB  - Since 1992, efforts have been made to combat onchocerciasis in Guatemala through
      mass distribution of ivermectin. The impact of the campaign is assessed by taking
      skin-snips from sentinel groups within selected communities. This method gives an
      estimate of the prevalence and intensity of infection, and thus the efficacy of
      the treatment. In some communities people are becoming reluctant to volunteer for
      skin-snipping, and so there is a need for an alternative technique that will give
      quantitative results. In most hyperendemic communities in Guatemala, biting
      blackflies are so ubiquitous that few people object to allowing 10 to 20 flies to
      engorge upon them. We examined data on the quantitative uptake of microfilariae
      by Simulium ochraceum before and after ivermectin distribution to see whether
      results similar to skin-snip data could be obtained. Counts of microfilariae
      ingested by S. ochraceum are compared to the numbers found in skin-snips from the
      same volunteers. In a group of 31 untreated infected persons, a skin-snip survey
      detected 64.5% positive, while feeding flies (vector microfilarial uptake, VmfU)
      detected 96.8%. Post-treatment, in a sample of 58 of whom 52 (89.7%) had a
      history of infection, both skin-snips and VmfU detected 54.2%. Vector blood meals
      contained more microfilariae than a mg of skin before treatment, but both
      recorded about equal numbers after treatment. When the data set was subdivided to
      compare samples taken at 2-3, 6-8 and 14-17 months post-treatment, the effect of
      ivermectin was still apparent at 6-8 months, but had virtually disappeared by 14
      months post-treatment. A surprising observation was that the flies ingested fewer
      microfilariae from treated persons than was expected from the skin densities as
      estimated by skin-snip. This effect lasted for over 8 months, and could indicate
      that ivermectin has a greater effect on transmission than previously suspected.
      We conclude that VmfU could be used as an alternative to skin-snipping, and
      discuss the ethical implications.

PMID- 9171844
TI  - Local health services: some lessons from their evolution in Bolivia.
AB  - For a decade, numerous projects in Bolivia have tried to put in practice the
      concept of local health systems. But, so far, no significant changes have been
      made and local health services still are the 'poor relation' of the system. The
      main components of the projects-expansion of health facilities, training of
      health personnel and institutional decentralization-were not designed to respond
      to the complexity of the problems encountered. Decentralization was implemented
      at the level of health districts but not accompanied by redefinition of functions
      at the central level, and challenged by civil servants' attempts to save their
      jobs. While training activities did introduce new methods and subjects, they were
      too often reduced to short workshops or seminars. Health facilities were built
      without regard for their significance beyond health care. A strategic approach is
      needed to adapt the planning process to the degree of liberty allowed by society.

PMID- 9171845
TI  - Serotype of Nigerian rotavirus strains.
AB  - Three hundred and fourteen stool samples collected from children < 5 years
      between December 1993 and August 1995 were analysed by PAGE, ELISA, PCR and Dot
      blot hybridization technique for electropherotype and serotype distribution of
      rotavirus infection among Nigerian paediatric patients. 14.3% of the children
      were positive for rotavirus antigen. Children aged 6-9 months were most often
      infected, accounting for 35.6% of all positive samples, 91.1% of rotavirus
      positive samples could be serotyped. Serotypes G2, G4 and G8 were not detected.
      Serotype G3 predominated (62.5%) in southern Nigeria, while mixed infection
      specificity was more widespread (63.6%) in northern Nigeria. The presence of some
      untypeable samples may indicate serotypes which the serotype-specific primers and
      cDNA probes used could not detect. Electropherotypes of 26 (57.7%) of the
      positive samples were determined. Two and 3 migration patterns were observed
      among the short and long-pattern electropherotypes, respectively. Implications
      for vaccine development and utilization in the country are discussed.

PMID- 9171846
TI  - Laryngeal involvement during post kala-azar dermal leishmaniasis in India.
AB  - Post kala-azar dermal leishmaniasis (PKDL) involving the mucus membranes is
      relatively rare on the Indian sub-continent. We describe 3 cases of PKDL
      presenting with hoarseness of voice. In one case the skin, nasal, oral,
      oropharyngeal and laryngeal mucosa had nodular and nodulo-ulcerative lesions; in
      the 2 other cases, genitalia and anorectal mucosa were also affected.
      Laryngoscopic examination revealed nodular lesions on the vocal cords. Biopsy
      smear and culture confirmed their leishmanial origin.

PMID- 9171847
TI  - Relationship of childhood protein-energy malnutrition and parasite infections in
      an urban African setting.
AB  - A clear understanding of protein-energy malnutrition (PEM), parasite infection
      and their interactions is essential in formulating health and development
      policies. We studied the prevalence of PEM indicators and the prevalence and/or
      intensity of infection in 558 Zairian children aged 4 months to 10 years.
      Multivariate analyses were used to estimate relationships between PEM indicators
      and parasitic infection. Stunting was found in 40.3% of children, wasting in 4.9%
      and kwashiorkor in 5.1%. The risk of stunting was significantly higher in
      children with Ascaris lumbricoides. The risk of wasting was higher in children
      with A. lumbricoides or Trichuris trichiura, whereas the risk of kwashiorkor was
      high with T. trichiura but very reduced in those with A. lumbricoides. Plasmodium
      infection was not related to nutritional indicators. These relationships
      highlight important interactions, both synergistic and antagonistic, between
      nutrition and parasites in central Africa.

PMID- 9171848
TI  - Olive oil aspiration pneumonia (lipoid) in children.
AB  - In the Asir region of south-western Saudi Arabia, nasal instillation of olive oil
      to infants and children in the recumbent position is practised to relieve nasal
      congestion. Aspiration of olive oil results in lipoid pneumonia resistant to
      antimicrobial treatment. A series of 5 children, aged 4-72 months, with olive oil
      induced lipoid pneumonia is presented. Clinical presentation included persistent
      coughing, tachypnoea, recurrent febrile illness and chest infections. The
      pulmonary radiological picture was mainly right middle lobar and perihilar
      infiltrates. Bronchial lavage and microscopic examination of the aspirate
      confirmed the presence of fat globules. The pneumonia resolved on treatment with
      steroids and physiotherapy in the form of clapping and vibrations. For infants
      and children in this area who present with persistent pulmonary infiltrates which
      are not responsive to antimicrobials, the differential diagnosis of not only
      animal fat (ghee, clarified butter) but also of olive oil lipoid pneumonia must
      be considered.

PMID- 9171849
TI  - Association of Chlamydia trachomatis antibodies with genital contact disease in
      women in Benin City, Nigeria.
AB  - The involvement of Chlamydia trachomatis in genital contact disease was assessed
      by measuring anti-chlamydial antibodies in the serum of 780 women aged 16-40
      years using the indirect haemagglutination test. These were compared to a control
      population consisting of 250 consenting housewives visiting General Practice
      Clinic (GPC) for other medical reasons. Test results showed an overall prevalence
      of 47% for indirect haemagglutination (IHA) chlamydial antibodies in women with
      genital contact disease. The average IHA titre was 143. The age group 21-25 years
      recorded the highest prevalence of 54%, with 55% giving a titre > or = 64. The
      control population gave a prevalence of 12% with no sample recording a titre < or
      = 64. These findings may indicate a need to routinely conduct investigations for
      chlamydial infection in all cases of genital contact disease in our environment.

PMID- 9171850
TI  - Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the
      effect of single treatment.
AB  - The efficacy and safety of ivermectin in the treatment of filariasis due to
      Wuchereria bancrofti was assessed by a meta-analysis of the results from 15
      published clinical trials. Seven hundred and forty-eight microfilaraemic patients
      were enrolled in 7 dose-finding and 8 comparative studies. Administered as a
      single dose, ivermectin induced nearly complete clearance of microfilariae from
      the blood from the first day to 30 days post-treatment, followed by gradual
      recurrence of microfilaraemia and increase in its intensity. Higher doses of
      ivermectin showed greater clearance effects and maintained lower microfilaraemia
      levels for a longer time. The adverse reactions caused by the drug were flu-like,
      transient, generally mild and well tolerated by patients. The frequency and
      intensity of adverse reactions were strongly associated with pretreatment
      microfilaria counts in the blood, but independent of dose. The findings of the
      meta-analysis suggest that ivermectin given at a single annual dose of 200
      micrograms/kg body weight or higher, whether or not in combination with DEC, has
      great potential for therapeutic strategies to control bancroftian filariasis.

PMID- 9171851
TI  - Birthweight distribution in rural north-west Burkina Faso.
AB  - Two thousand and twenty-six delivery records from 1987 to 1989 in 5 rural health
      units in North Western Burkina Faso were analysed. The mean birthweight was 2899
      g, with an overall incidence of low birthweight of 9.3%. Increasing birth order
      from 1 to 3 was associated with increasing birthweight; for birth orders > 3,
      birthweight was relatively constant. There is a marked seasonal variation in
      birthweight, with a decrease in the rainy season and an increase during the dry
      season. These findings are compared with other African populations. The
      anthropometric measurements of these newborns were slightly lower than standards
      from industrialized North America.

PMID- 9171852
TI  - The effect of aging on the utilization of chemotherapy for metastatic breast
      cancer: a population-based study.
AB  - Older women (i.e., > or = 65 years of age) receive less adjuvant chemotherapy
      than younger women, in part because chemotherapy has been less effective in
      postmenopausal than premenopausal women in clinical trials. Metastatic breast
      cancer, however, does not respond differently to chemotherapy by age. Therefore,
      to evaluate further the effect of age on chemotherapy utilization, we conducted a
      population-based study of the treatment of metastatic breast cancer. Patients (n
      = 132) were identified by cross-tabulating death certificates from 1984 to 1991
      with breast cancer cases in the Washington County Cancer Registry. Treatment
      information was obtained from the Tumor Registry of the Washington Country
      Hospital and Hospital medical records. Forty patients (74%) < 65 years old
      received chemotherapy compared to 11 (42%) 65-74 and 6 (12%) > or = 75 (p <
      0.0001). Adjusting for other medical conditions and whether or not the patient
      saw a medical oncologist, there was still a significant effect of age in patients
      > or = 75 (p < 0.001) and a trend (p = 0.17) for patients 65-74. The different
      patterns of chemotherapy utilization were not associated with survival
      differences. Radiation therapy was also utilized significantly less frequently in
      older than younger patients, but the age effect was not as pronounced as with
      chemotherapy. There was no age effect on the utilization of hormonal therapy.
      Less frequent utilization of chemotherapy in older patients is probably caused by
      a combination of patient and physician factors and may result in less effective
      palliation for older patients.

PMID- 9171853
TI  - The first clinical pilot study of roquinimex (Linomide) in cancer patients with
      special focus on immunological effects.
AB  - Roquinimex (Linomide) has been demonstrated to suppress tumor growth in animal
      models. The effect is at least in part related to enhanced numbers and activity
      of natural killer (NK) cells. In this clinical pilot study, roquinimex was given
      at increasing doses (0.05 mg/kg to 0.6 mg/kg) to 13 patients (performance status
      0-3) with various malignant disorders. Immunology parameters were followed and
      side effects were observed during the study. The plasma pharmacokinetics of
      roquinimex was studied at the 0.2 mg/kg dose level. The clinical side effects
      were dominated by musculoskeletal discomfort, nausea, and pain. No significant
      hematological or biochemical toxicity was observed. Pharmacokinetic analysis at
      the 0.2 mg/kg dose level revealed a Cmax of 4.0 mumol/L at tmax of 1.2 hr and an
      elimination half-life of 42 hr. Increased numbers of phenotypic NK cells,
      activated T (DR+CD4+) cells, and monocytes were observed after administration of
      roquinimex compared with pretreatment values. Roquinimex seems to be an active
      immunomodulator with manageable toxicity. Further exploration of therapeutic
      efficacy is warranted.

PMID- 9171854
TI  - Activity of the enzymes participating in purine metabolism of cancerous and
      noncancerous human kidney tissues.
AB  - In this study, activity of some of the key enzymes participating in purine
      metabolism was measured in cancerous and noncancerous human kidney tissues from
      18 patients with renal cell carcinoma. Twelve cancerous tissues were at stage T1
      T2 and 6 tissues were at stage T3-T4. Adenosine deaminase (ADA) and guanase (GUA)
      activity was increased and xanthine oxidase (XO) activity decreased in cancerous
      tissues compared to noncancerous ones. No difference was, however, found between
      5'-Nucleotidase (5'-NT) activity of the tissues. There were also no statistically
      meaningful differences between the enzyme activities of the cancerous tissues at
      stage T1-2 and T3-4. Results suggest that the changes observed in the activity of
      the enzymes participating in purine metabolism result from accelerated DNA
      turnover in the cancerous tissues and cells, and these changes might provide
      selective advantage, possibly by causing acceleration of salvage pathway
      activity, to the cancer cells to grow and develop more rapidly.

PMID- 9171855
TI  - ADP-ribosylation of serum proteins: elevated levels in neoplastic cases due to
      altered NAD/ADP-ribose metabolism.
AB  - ADP-ribosylation of human serum proteins was studied in various groups of
      disorders. In most of these groups, the extent of ADP-ribosylation did not show a
      divergence from the group of normal controls. Neoplastic diseases revealed,
      however, a unique group, with more than fivefold increases in ADP-ribosylation
      levels over the other groups. Blood samples with high levels of ADP-ribosylation
      revealed, in general, increased serum NAD glycohydrolase activities and low
      levels of serum NAD.

PMID- 9171856
TI  - A case of melanoma concurrent with progressive systemic sclerosis.
AB  - The association between progressive systemic sclerosis (PSS; scleroderma) and
      malignancy has been a controversial issue in the literature. The present report
      describes a rare case of concurrent malignant melanoma and PSS. A literature
      review suggests a possible connection between these two conditions.

PMID- 9171857
TI  - Economic analyses of phase III cooperative cancer group clinical trials: are they
      feasible?
AB  - Both economic and clinical evaluations of new pharmaceutical agents are important
      to physicians who practice in the current health care environment. While
      cooperative cancer groups carry out large-scale phase III clinical evaluations of
      these agents, few cooperative group studies incorporate economic analyses because
      of concerns over overburdening of data management, investigators, and statistical
      center personnel. In this study, we describe the results and operational
      considerations of one of the first completed economic analyses of a phase III
      cooperative group trial of the Eastern Cooperative Oncology Group (ECOG). We
      developed an economic model estimating economic benefits of yeast-derived
      granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjunct therapy for
      adult patients (56-70 years) with acute myelogenous leukemia. Clinical data were
      based on prospectively collected information from a recently reported double
      blind phase III multi-institutional study carried out by ECOG. Retrospective
      economic data were obtained from financial information systems at our hospital,
      one of the study sites. The cost-minimization analyses were based on the
      perspective of a third-party payer. Indirect costs related to loss of earnings by
      patients and caregivers as well as quality-of-life adjustments were not
      incorporated into the model. Clinical trial results indicated that patients
      treated with GM-CSF had shorter times to recovery of absolute neutrophil count of
      500 cells/mm3 and 1000 cells/mm3 and fewer serious infections than patients who
      received placebo following induction chemotherapy, while no significant
      differences were noted in red blood cell and platelet transfusion dependency,
      toxicities, and duration of hospitalization. The economic model estimated that
      the group treated with GM-CSF was estimated to have lower costs of care,
      associated with lower frequencies of serious infections and lower overall
      infection-related costs. Sensitivity analyses indicated that these results held
      true over a wide range of estimates of costs and infection rates. Prospective
      economic analyses of phase III cooperative cancer group clinical trials have not
      been completed to date. Strategies that are not likely to overburden data
      managers and statistical center personnel are possible to devise. However, these
      studies require careful planning and coordination between clinical trialists,
      economists, and health services researchers.

PMID- 9171858
TI  - Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic
      patients with cancer.
AB  - Until recently, febrile neutropenic patients were treated with intravenous
      antibiotics in inpatient settings. Because of work completed in the last several
      years by various investigators, identification of a low-risk group of febrile,
      neutropenic patients has allowed successful treatment with both parenteral and
      oral antibiotics in an ambulatory environment. This accomplishment has been
      facilitated by advances in broad-spectrum antibiotics with long half-lives and
      stabilities, the introduction of the quinolones providing oral antipseudomonal
      activity, home health care, improvements in vascular access devices, and
      technically enhanced antibiotic delivery systems. This review focuses on the
      rationale of risk stratification and the progress made in treating low-risk
      febrile neutropenic patients as outpatients.

PMID- 9171860
TI  - Managing patients and families at the ending of life: hospice assumptions,
      structures, and practice in response to staff stress.
AB  - Hospice programs do not identify burnout as a significant staff problem, even
      though there are many significant stressors for staff members doing hospice work.
      Hospices offer support in a wide variety of ways and settings through their human
      resources management. All this support is predicated on the assumption that the
      nature of the work requires it, and that hospice programs are responsible to
      provide it for staff. Certainly, in a rapidly changing health care environment
      that increasingly is expecting health care providers to do more with less, all
      systems of health care delivery will need to examine the management of stress and
      learn better how to provide a healthy work environment for those who deliver
      health care. The experience of hospices offers much to assist this process.

PMID- 9171859
TI  - Recent insights into the functions of the retinoblastoma susceptibility gene
      product.

PMID- 9171861
TI  - The status of ultrasound and color Doppler imaging for the early detection of
      ovarian carcinoma.
AB  - Noninvasive imaging techniques such as ultrasound and color doppler imaging have
      been evaluated during the last decade for their ability to detect organ-confined
      curable ovarian cancer. While sensitivities approaching 100% can be achieved by
      these techniques, their specificities and the frequent invasive procedures
      required to confirm the abnormal sonographic findings have led to caution
      regarding the widespread use of ultrasound screening for ovarian cancer. These
      data are reviewed, as well as the NIH Consensus Panel on ovarian cancer's
      recommendation that routine screening for ovarian carcinoma should not be carried
      out at this time. Hereditary ovarian cancer syndromes account for approximately 5
      10% of the cases. Many of the genes responsible for these syndromes have recently
      been elucidated. Due to the significant increase in the risk of ovarian cancer in
      these families, many screening studies have focused on this patient population.
      Findings from these trials, as well as studies on the psychological impact of
      screening are presented.

PMID- 9171862
TI  - Initial surgical management of advanced epithelial ovarian cancer.

PMID- 9171863
TI  - The role of chemotherapy in the management of celomic epithelial carcinoma of the
      ovary.

PMID- 9171864
TI  - The role of high-dose chemotherapy with hematopoietic stem cell support in the
      treatment of patients with epithelial ovarian carcinoma.

PMID- 9171865
TI  - 17 beta-(3-furyl)-5 beta-androstane-3 beta, 14 beta, 17 alpha-triol (PST 2238). A
      very potent antihypertensive agent with a novel mechanism of action.

PMID- 9171866
TI  - Potent noncovalent thrombin inhibitors that utilize the unique amino acid D
      dicyclohexylalanine in the P3 position. Implications on oral bioavailability and
      antithrombotic efficacy.
AB  - In an effort to prepare orally bioavailable analogs of our previously reported
      thrombin inhibitor 1, we have synthesized a series of compounds that utilize the
      unique amino acid D-dicyclohexylalanine as a P3 ligand. The resulting compounds
      are extremely potent and selective thrombin inhibitors, and the N-terminal Boc
      derivative 8 exhibited excellent oral bioavailability and pharmacokinetics in
      both rats and dogs. The des-Boc analog 6 was not orally bioavailable in rats. The
      high level of oral bioavailability observed with 8 appears to be a direct
      function of its increased lipophilicity versus other close analogs. Although
      increased lipophilicity may serve to increase the oral absorption of tripeptide
      thrombin inhibitors, it also appears to have detrimental effects on the
      antithrombotic properties observed with the compounds. Compound 6 performed
      extremely well in our in vivo antithrombotic assay, while the much more
      lipophilic but essentially equipotent analog 8 performed poorly. We have found
      that in general with this series of thrombin inhibitors as well as with other
      unreported series, increased lipophilicity and the associated increases in plasma
      protein binding have detrimental effects on 2X APTT values and subsequent
      performance in in vivo antithrombotic models.

PMID- 9171867
TI  - Dual metalloprotease inhibitors: mercaptoacetyl-based fused heterocyclic
      dipeptide mimetics as inhibitors of angiotensin-converting enzyme and neutral
      endopeptidase.
AB  - A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were
      generated and incorporated as conformationally restricted dipeptide surrogates in
      mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin
      converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in
      vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent
      blood pressure lowering in a variety of animal models characterized by various
      levels of plasma renin activity and significantly potentiated urinary sodium,
      ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency
      and duration of action, compound 1a (BMS-186716) was advanced into clinical
      development for the treatment of hypertension and congestive heart failure.

PMID- 9171868
TI  - Aroyl(aminoacyl)pyrroles, a new class of anticonvulsant agents.
AB  - 2-Aroyl-4-(omega-aminoacyl)- (4) and 4-aroyl-2-(omega-aminoacyl)pyrroles (9)
      represent a new, structurally novel class of anticonvulsant agents. Compounds of
      type 4 were prepared by Friedel-Crafts acylation of a 2-aroylpyrrole with an
      omega-chloroacyl chloride followed by displacement of the chloro group by a
      primary or secondary amine. Compounds of type 9 were prepared by Friedel-Crafts
      aroylation of a 2-(omega-chloroacyl)pyrrole followed by displacement by an amine.
      These compounds were active in the mouse and rat maximal electroshock tests but
      not in the mouse metrazole test. The lead compound, RWJ-37868, 2-(4
      chlorobenzoyl)-4-(1-piperidinyl-acetyl)-1,3,5-trimethylpyrrole++ + (4d), showed
      potency and therapeutic index comparable to those of phenytoin and carbamazepine
      and greater than those of sodium valproate. This compound blocked bicuculline
      induced seizures, did not elevate seizure threshold following iv infusion of
      metrazole, and blocked influx of Ca2+ ions into cerebellar granule cells induced
      by K+ or veratridine.

PMID- 9171869
TI  - Substituted hexahydrobenzo[f]thieno[c]quinolines as dopamine D1-selective
      agonists: synthesis and biological evaluation in vitro and in vivo.
AB  - A series of substituted 9,10-dihydroxyhexahydrobenzo[f]thieno[c]quinolines
      (TB[f]Q), varying with respect to the position of the thiophene relative to the
      benzo[f]quinoline core and the nature and position of the substituent on the
      thiophene, were prepared and evaluated for their affinity and selectivity for the
      dopamine D1-like receptor. The thieno[3,2-c]B[f]Q regioisomers bearing a small
      alky1 (C1-C3) substituent at the 2 position were potent (Ki < 20 nM) and
      selective (D2/D1 > 50) D1 agonists with close to full agonist activity (IA >
      85%). The compounds were resolved and found to exhibit a high level of
      enantiospecificity in their interaction with the D1 receptor. Selected compounds
      were tested in vivo in the 6-OHDA rodent model of Parkinson's disease and for
      their liability to produce seizure-like activities in mice. (5aR)-trans-2-Propyl
      4,5,5a,6,7, 11b-hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene-9,10-diol
      (5) emerged as the compound with the best overall in vivo profile in terms of
      potency (ED50 = 0.04 mumol/kg) and safety.

PMID- 9171870
TI  - Synthesis and pharmacological properties of a close analogue of an antithrombotic
      pentasaccharide (SR 90107A/ORG 31540).
AB  - The synthetic pentasaccharide (1) corresponding to the heparin sequence which
      binds to, and activates, antithrombin III (AT III) is a potent antithrombotic
      compound in several animal models of venous thrombosis. We describe here the
      preparation and the pharmacological properties of 34, an analogue of
      oligosaccharide 1 with the latter's N-sulfates being replaced by sulfate esters
      and hydroxyl groups being methylated. These structural modifications allow a
      simpler and more efficient synthesis of such anionic oligosaccharides. Affinity
      for human AT III, anti-factor Xa activity, ability to inhibit thrombin
      generation, antithrombotic activity in a rat model of venous thrombosis, and
      elimination half-life in the rat have been determined for 1 and 34. Surprisingly,
      introduction of O-sulfates in place of N-sulfates, and methylation of hydroxyl
      groups, contributes to reinforce the binding to AT III, resulting in an improved
      pharmacological profile.

PMID- 9171871
TI  - Anticancer and antiviral effects and inactivation of S-adenosyl-L-homocysteine
      hydrolase with 5'-carboxaldehydes and oximes synthesized from adenosine and sugar
      modified analogues.
AB  - Selectively protected adenine nucleosides were converted into 5'-carboxaldehyde
      analogues by Moffatt oxidation (dimethyl
      sulfoxide/dicyclohexylcarbodiimide/dichloroacetic acid) or with the Dess-Martin
      periodinane reagent. Hydrolysis of a 5'-fluoro-5'-S-methyl-5'-thio (alpha-fluoro
      thioether) arabinosyl derivative also gave the 5'-carboxaldehyde. Treatment of 5'
      carboxaldehydes with hydroxylamine [or O-(methyl, ethyl, and
      benzyl)hydroxylamine] hydrochloride gave E/Z oximes. Treatment of purified oximes
      with aqueous trifluoroacetic acid and acetone effected trans-oximation to provide
      clean samples of 5'-carboxaldehydes. Adenosine (Ado)-5'-carboxaldehyde and its 4'
      epimer are potent inhibitors of S-adenosyl-L-homocysteine (AdoHcy) hydrolase.
      They bind efficiently to the enzyme and undergo oxidation at C3' to give 3'-keto
      analogues with concomitant reduction of the NAD+ cofactor to give an inactive,
      tightly bound NADH-enzyme complex (type I cofactor-depletion inhibition). Potent
      type I inhibition was observed with 5'-carboxaldehydes that contain a ribo cis
      2',3'-glycol. Their oxime derivatives are "proinhibitors" that undergo enzyme
      catalyzed hydrolysis to release the inhibitors at the active site. The 2'-deoxy
      and 2'-epimeric (arabinosyl) analogues were much weaker inhibitors, and the 3'
      deoxy compounds bind very weakly. Ado-5'-carboxaldehyde oxime had potent
      cytotoxicity in tumor cell lines and was toxic to normal human cells. Analogues
      had weaker cytotoxic and antiviral potencies, and the 3'-deoxy compounds were
      essentially devoid of cytotoxic and antiviral activity.

PMID- 9171872
TI  - 1,2-Diarylpyrroles as potent and selective inhibitors of cyclooxygenase-2.
AB  - Series of 1,2-diarylpyrroles has been synthesized and found to contain very
      potent and selective inhibitors of the human cyclooxygenase-2 (COX-2) enzyme. The
      paper describes short and practical syntheses of the target molecules utilizing
      the Paal-Knorr reaction. Electrophilic substitution on 1 proceeds in a
      regioselective fashion, and the method was used to generate a number of
      tetrasubstituted pyrroles. Detailed SAR on the series has been studied by
      modifications of the aryl rings and the substituents in the pyrrole ring.
      Diarylpyrrole 1 is a very potent (COX-2, IC50 = 60 nm) and selective (COX-1/COX-2
      = > 1700) inhibitor whereas the isomeric 2 is completely inactive against COX-2.
      Modifications of the substituents on the fluorophenyl ring in 1 yields very
      potent inhibitors of COX-2 (IC50 = 40-80 nm) with excellent selectivity (1200 to
      > 2500) vs COX-1. Analog 20 containing a sulfonamide group is an excellent
      inhibitor of COX-2 with an IC50 of 14 nm. Tetrasubstituted pyrroles containing
      groups such as COCF3, SO2CF3, or CH2OAr at position 3 in the pyrrole ring give
      excellent inhibitors (COX-2, IC50 = 30-120 nm). In vivo testing in the
      carrageenan-induced paw edema model in the rat establishes that the 1,2
      diarylpyrroles are orally active antiinflammatory agents. Compound 3 is the most
      potent inhibitor of edema with an ED50 of 4.7 mpk.

PMID- 9171873
TI  - 1,2-Diarylimidazoles as potent, cyclooxygenase-2 selective, and orally active
      antiinflammatory agents.
AB  - Series of 1,2-diarylimidazoles has been synthesized and found to contain highly
      potent and selective inhibitors of the human COX-2 enzyme. The paper describes a
      short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles.
      Different portions of the diarylimidazole (I) were modified to establish SAR.
      Systematic variations of the substituents in the aryl ring B have yielded very
      potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2
      enzyme. The study on the influence of substituents in the imidazole ring
      established that a CF3 group at position 4 gives the optimum oral activity. A
      number of the diarylimidazoles showed excellent inhibition in the adjuvant
      induced arthritis model (e.g., ED50 = 0.02 mpk for 22 and 34). The
      diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 =
      9-30 mpk) and hyperalgesia (ED50 = 11-40 mpk). Several orally active
      diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

PMID- 9171874
TI  - Synthesis and structure-activity relationships of a new model of arylpiperazines.
      2. Three-dimensional quantitative structure-activity relationships of hydantoin
      phenylpiperazine derivatives with affinity for 5-HT1A and alpha 1 receptors. A
      comparison of CoMFA models.
AB  - A series of 48 bicyclohydantoin-phenylpiperazines (1-4) with affinity for 5-HT1A
      and alpha 1 receptors was subjected to three-dimensional quantitative structure
      affinity relationship analysis using comparative molecular field analysis
      (CoMFA), in order to get insight into the structural requirements that are
      responsible for 5-HT1A/alpha 1 selectivity. Good models (high cross-validation
      correlations and predictive power) were obtained for 5-HT1A and alpha 1
      receptors. The resulting 3D-QSAR models rationalize steric and electrostatic
      factors which modulate binding to 5-HT1A and alpha 1 receptors. A comparison of
      these models gives an additional understanding for 5-HT1A/alpha 1 selectivity:
      (a) Substitution at the ortho position by a group with negative potential is
      favorable to affinity for both receptors. (b) The meta position seems to be
      implicated in 5-HT1A/alpha 1 selectivity. While the 5-HT1A receptor is able to
      accommodate bulky substituents in the region of its active site, the steric
      requirements of the alpha 1 receptor are more restricted (optimum volume of
      substituent 11-25 A3). (c) For both receptors the para position represents a
      region where the volume accessible by the ligands is limited. (d) The hydantoin
      moiety and the side chain length seem to modulate not only the affinity but also
      5-HT1A/alpha 1 selectivity. The 3D-QSAR models reveal an useful predictive
      information for the design of new selective ligands.

PMID- 9171875
TI  - Halogenated 4-(phenoxymethyl)piperidines as potential radiolabeled probes for
      sigma-1 receptors: in vivo evaluation of [123I]-1-(iodopropen-2-yl)-4-[(4
      cyanophenoxy)methyl]pip eri dine.
AB  - Several halogenated 4-(4-phenoxymethyl)piperidines were synthesized as potential
      sigma receptor ligands. The affinity and selectivity of these compounds were
      determined using in vitro receptor binding assays, and their log P values were
      estimated using HPLC analysis. The effect of various N-substituents on the sigma
      1 and sigma-2 dissociation constants was examined. These substituents included
      fluoroalkyl, hydroxyalkyl, iodopropenyl, and selected ortho-, meta-, and para
      substituted benzyl groups. Also determined were the effects of various moieties
      on the phenoxy ring; specifically 4-iodo, 4-bromo, 4-nitro, 4-cyano, 3-bromo, and
      pentafluoro substituents were examined. The ranges in the dissociation constants
      of these compounds for sigma-1 and sigma-2 receptors were 0.38-24.3 and 3.9-361
      nM, respectively. The ratio of Ki (sigma-2/sigma-1) ranged from 1.19 to 121. One
      of the most promising of the iodinated ligands, 1-(trans-iodopropen-2-yl)-4-[(4
      cyanophenoxy)methyl]piperidi ne (4), was labeled with 123I and studied in vivo in
      adult male rats. High uptake and good retention of radioactivity was observed in
      the brain and many other organs known to possess sigma receptors. Blocking
      studies revealed high specific binding of [123I]-4 to sigma receptors in the
      brain, lung, kidney, heart, muscle, and other organs known to possess these
      sites. These results indicate that [123I]-4 and other halogenated 4
      (phenoxymethyl)piperidines of this series may provide useful probes for in vivo
      tomographic studies of sigma receptors.

PMID- 9171876
TI  - Anesthetic activity of novel water-soluble 2 beta-morpholinyl steroids and their
      modulatory effects at GABAA receptors.
AB  - (3 alpha,5 alpha)-3-Hydroxypregnan-20-ones and (3 alpha,5 alpha)-3
      hydroxypregnane-11,20-diones bearing a 2 beta-morpholinyl substituent were
      synthesized, and the utility of these steroids as anesthetic agents was evaluated
      through determination of their potency and duration of hypnotic activity in mice
      after intravenous administration. Alkylation of the morpholinyl substituent or
      chlorination at C-21 afforded the novel amino steroids (2 beta,3 alpha,5 alpha)-3
      hydroxy-2-(2,2-dimethyl-4-morpholinyl)-pregnane-11,20-dione (19) and (2 beta,3
      alpha,5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one (37) that were
      more potent and advantageously produced shorter sleep times than related
      compounds which were previously reported. Furthermore, salts of these and other
      amino steroids generally retained good aqueous solubility. In a radioligand
      binding assay the compounds inhibited the specific binding of [35S]-tert-butyl
      bicyclophosphorothionate to rat whole brain membranes, and in an
      electrophysiological assay they potentiated GABAA receptor-mediated currents
      recorded from voltage-clamped bovine chromaffin cells. These in vitro results are
      consistent with the anesthetic activity of the amino steroids being related to
      their modulatory effects at GABAA receptors.

PMID- 9171877
TI  - Structure-activity relationships of N2-aryl-3-(isoxazolylsulfamoyl)-2
      thiophenecarboxamides as selective endothelin receptor-A antagonists.
AB  - We report here that N2-aryl-3-(isoxazolylsulfamoyl)-2-thiophenecarboxamides are
      potent and selective small molecule ETA receptor antagonists. The aryl group was
      subjected to extensive structural modification. With monosubstitution, the para
      position was most useful in increasing potency, with methyl being preferred. With
      disubstitution, 2,4-disubstitution further enhanced activity with methyl or cyano
      groups being preferred at the 2-position. In this series, a benzo-[d][1,3]dioxole
      group is equivalent to a 4-methyl group in in vitro activity and afforded the
      compounds with both in vivo activity and moderate half-lives.

PMID- 9171878
TI  - Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A
      selective antagonist.
AB  - Previously we reported the discovery of amidothiophenesulfonamides as endothelin
      receptor-A antagonists with high potency and selectivity. Replacement of an amide
      group in this class of compounds with an acetyl group maintained the in vitro
      binding affinity and in vivo activity while providing a compound with oral
      bioavailability and longer duration of action. The optimal compound discovered
      during these studies, 15q (TBC11251), binds competitively to human ETA receptors
      with a Ki of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM).
      This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with
      a Ki of 0.686 nM and a pA2 of 8.0. The compound has a serum half-life in the rat
      and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of
      the most selective ETA antagonists reported and therefore is suitable for
      additional pharmacological and clinical investigation of the role of ETA
      receptors in diseases.

PMID- 9171879
TI  - Chemometric methodologies in a quantitative structure-activity relationship
      study: the antibacterial activity of 6-aminoquinolones.
AB  - The paper illustrates the chemometric strategies appropriate for extracting
      information from a large amount of biological data regarding the antibiotic
      activity of 6-aminoquinolones. The unique framework based on principal component
      analysis, projection onto latent structures, and response surface methodologies
      permits the structure-activity correlations to be shown and to suggest new
      compounds for further testing. The low activity of the suggested molecules points
      out the limitations of quantitative structure-activity relationship models when
      the training set is not properly designed in order to balance all the structural
      variations taken into account.

PMID- 9171880
TI  - Design, synthesis, and evaluation of tetrahydropyrimidinones as an example of a
      general approach to nonpeptide HIV protease inhibitors.
AB  - Re-examination of the design of the cyclic urea class of HIV protease (HIVPR)
      inhibitors suggests a general approach to designing novel nonpeptide cyclic HIVPR
      inhibitors. This process involves the inversion of the stereochemical centers of
      the core transition-state isostere of the linear HIVPR inhibitors and cyclization
      of the resulting core using an appropriate cyclizing reagent. As an example, this
      process is applied to the diamino alcohol class of HIVPR inhibitors to give
      tetrahydropyrimidinones. Conformational analysis of the tetrahydropyrimidinones
      and modeling of its interaction with the active site of HIVPR suggested
      modifications which led to very potent inhibitors of HIVPR (24 with a Ki = 0.018
      nM). The X-ray crystallographic structure of the complex of 24 with HIVPR
      confirms the analysis and modeling predictions. The example reported in this
      study and other examples that are cited indicate that this process may be
      generally applicable to other linear inhibitors.

PMID- 9171881
TI  - 7-Spiroindanyl derivatives of naltrexone and oxymorphone as selective ligands for
      delta opioid receptors.
AB  - A series consisting of spiroindanyl (5-7), benzospiroindanyl (8-10), and
      spiroperinaphthyl (11) derivatives of naltrexone and oxymorphone were synthesized
      in order to investigate the role of an orthogonal-oriented "address" for delta
      opioid receptors. All of the ligands exhibited a preference for delta receptors
      in vitro. The 7-benzospiroindanyl derivative 8 (BSINTX) was the most selective
      delta opioid receptor antagonist in vitro. In mice BSINTX antagonized the delta 1
      selective agonist, [D-Pen2,D-Pen5]enkephalin without significantly affecting the
      antinociceptive potency of delta 2, mu, and kappa agonists. The results of this
      study are consistent with an orthogonally-oriented address favoring delta 1
      activity.

PMID- 9171882
TI  - Modulation of melphalan resistance in glioma cells with a peripheral
      benzodiazepine receptor ligand-melphalan conjugate.
AB  - Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of
      mitochondria, and their density is increased in brain tumors. Thus, they may
      serve as a unique intracellular and selective target for antineoplastic agents. A
      PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for
      cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized
      by coupling of two key intermediates: 4-[bis(2-chloroethyl)-amino]-L
      phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro
      1,3- dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor
      binding displacement assays in rat brain and glioma cells, 9 had appreciable
      binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50
      values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety
      of rat and human brain tumor cell lines. In some of the cell lines tested
      including rat and human melphalan-resistant cell lines, 9 demonstrated
      appreciable cytotoxicity with IC50 values in the micromolar range, lower than
      that of melphalan alone. The enhanced activity of 9 may reflect increased
      membrane permeability, increased intracellular retention, or modulation of
      melphalan's mechanisms of resistance. The combined data support additional
      studies to determine how 9 may modulate melphalan resistance, its mechanisms of
      action, and if target selectivity can be achieved in in vivo glioma models.

PMID- 9171883
TI  - Synthesis, structure, and antiproliferative activity of selenophenfurin, an
      inosine 5'-monophosphate dehydrogenase inhibitor analogue of selenazofurin.
AB  - The synthesis and biological activity of selenophenfurin (5-beta-D
      ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of
      selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate
      (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated
      regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5
      diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3
      carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The
      structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and
      computational studies. Selenophenfurin proved to be antiproliferative against a
      number of leukemia, lymphoma, and solid tumor cell lines at concentrations
      similar to those of selenazofurin but was more potent than the thiophene and
      thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with
      selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an
      increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%).
      The results obtained confirm the hypothesis that the presence of heteroatoms such
      as S or Se in the heterocycle in position 2 with respect to the glycosidic bond
      is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in
      this type of C-nucleosides.

PMID- 9171884
TI  - Biological and conformational examination of stereochemical modifications using
      the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on
      human melanocortin receptors.
AB  - Examination of conformationally constrained melanotropin peptide (Ac-Nle4-c[Asp5
      His-Phe7-Arg-Trp9-Ala-Lys]-NH2) on four human melanotropin receptors (hMC1R,
      hMC3R, hMC4R, and hMC5R) resulted in identifying the importance of ligand
      stereochemistry at positions 5, 7, and 9 for agonist binding affinity and
      receptor selectivity. A trend in ligand structure-activity relationships emerged
      for these peptides, with the hMC1R and hMC4R possessing similar tendencies, as
      did the hMC3R and hMC5R. alpha-MSH (Ac-Ser-Tyr-Ser-Met4-Glu-His-Phe7-Arg-Trp-Gly
      Lys-Pro-Val-NH2), NDP-MSH (Ac-Ser-Tyr-Ser-Nle4-Glu-His-D-Phe7-Arg-Trp-Gly-Lys-Pro
      Val-NH2), and MTII (Ac-Nle4-c[Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)-NH2) were also
      examined at each of these melanocortin receptors. Interestingly, the linear NDP
      MSH possessed greater binding affinity for the hMC3R and hMC5R than did the
      cyclic analogue MTII. The peptide Ac-Nle-c[Asp-His-Phe-Arg-D-Trp9-Ala-Lys]-NH2
      demonstrated the greatest differentiation in binding affinity between the hMC1R
      and hMC4R (78-fold). Analogue Ac-Nle-c[Asp-His-Phe7-Arg-Trp-Ala-Lys]-NH2 resulted
      in micromolar binding affinity (or greater) at the hMC3R and hMC5R, demonstrating
      the importance of D-Phe7 for ligand binding potency at these receptors. Ac-c[Asp
      His-Phe-Arg-Trp-Ala-Lys]-NH2 resulted in loss of binding affinity at the hMC5R,
      implicating the importance of Nle4 (or a hydrophobic residue in this position)
      for binding to this receptor. Ac-Nle-c[D-Asp5-His-Phe-Arg-Trp-Ala-Lys]-NH2 was
      unable to competitively displace [125I]NDP-MSH binding at micromolar
      concentrations on the hMC3R and hMC5R, suggesting the importance of chirality of
      Asp5 either for ligand-receptor interactions or for orientation of the side chain
      lactam bridge and the structural integrity of the peptide conformation. Energy
      calculations performed for these peptides resulted in the identification of a low
      energy ligand conformer family that is common to all the ligands. The differences
      in ligand binding affinities observed in this study are postulated to be a result
      of different ligand-receptor complexed interactions and not solely to the ligand
      structure.

PMID- 9171885
TI  - Synthesis and oral efficacy of a 4-(butylethylamino)pyrrolo[2,3-d]pyrimidine: a
      centrally active corticotropin-releasing factor1 receptor antagonist.
AB  - The syntheses of a centrally active nonpeptide CRF1 receptor antagonist 2,
      butylethyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo [2,3-d]pyrimidin-4
      yl]amine (CP-154,526), and its analogs 11-14 and [3H]-2 are reported. The in
      vitro CRF1 receptor binding affinity in the series 2, the pharmacokinetic
      properties of 2 in rats, and the anxiolytic-like effects of orally administered 2
      are presented.

PMID- 9171886
TI  - Arylcarbamate derivatives of 1-piperidineethanol as potent ligands for 5-HT4
      receptors.
AB  - A series of carbamate derivatives (7) of 2-(1-piperidinyl)ethyl 4-amino-5-chloro
      2-methoxybenzoates, which have been described as potent agonists and antagonists
      of 5-HT4 receptors, were synthesized. They were evaluated using radioligand
      binding assays with [3H]GR 113808, a 5-HT4 receptor selective ligand, in the rat
      striatum and the electrically stimulated myenteric plexus longitudinal muscle of
      the guinea pig. In contrast to the previously described ester derivatives, a drop
      in the affinity for 5-HT4 receptors was observed and the compounds were inactive
      as agonists in the guinea pig ileum preparation. Unexpectedly, the ortho
      substituted carbamates 8b,c (R' = H, RO = MeO or EtO, R" = H) had nanomolar
      affinity for 5-HT4 receptors (Ki = 8.9 +/- 0.5 and 2.6 +/- 0.4 nM, respectively).
      As reported previously, the cis- or trans-3,5-dimethyl substitution of piperidine
      (8n,o) was particularly favorable (Ki = 1.1 +/- 0.6 nM for both isomers). 8c is
      an antagonist equipotent to the 5-HT4 receptor antagonist SDZ 205-557 (1).

PMID- 9171887
TI  - Regulatory elements of the mb-1 gene encoding the Ig-alpha component of the human
      B-cell antigen receptor.
AB  - The mb-1 gene encodes the Ig-alpha component of the B-cell antigen receptor. It
      is specifically expressed in pre-B and mature B cells but not in plasma cells
      losing membrane Ig (mIg) expression. We looked for transcriptional regulatory
      elements within a 12 kb genomic fragment. A strong promoter activity was found in
      a 591 bp fragment harboring consensus binding sites for known transcription
      factors including Ets, EBF/BlyF, LyF1/micro B and Spl. It was able to drive
      transcription of a reporter gene in the absence of any additional enhancer and
      was mostly active in B lymphocytes not in plasma cells or T cells. Although no
      fragment from the mb-1 gene displayed enhancer activity in combination with
      either the SV40, a Ig VH or a Ig VL promoter, a 1078 bp fragment corresponding to
      the 5' part of the gene behaved as a strong enhancer in either orientation in
      constructs driven by the mb-1 promoter itself. Deletions within this fragment
      allowed to delineate shorter sequences with enhancer activity upstream the first
      exon. The tissue-restricted, promoter-restricted and stage-specific activity of
      this 5' flanking region suggests that it is the main regulatory element of the mb
      1 gene.

PMID- 9171888
TI  - Extraordinary stability of IgE-binding Parietaria pollen allergens in relation to
      chemically bound flavonoids.
AB  - It is known that the skin-active and IgE-binding components in Parietaria pollen
      extracts are not restricted to the predominant protein allergens of M(r) 12000
      15000, but are present as well among the naturally occurring constituents of M(r)
      < 10000. Indeed, the IgE-binding Parietaria pollen components are quite
      heterogeneous, ranging from high- to low-molecular mass, whereby the IgE-binding
      epitopes display an unusual chemical stability. Furthermore, the pollen of
      Parietaria species demonstrably contain a high proportion of flavonoid pigments.
      Since these pollen grains cannot be collected entirely free from non-pollen plant
      parts, the usual allergenic extracts of Parietaria encompass both the
      polyphenolic substrate molecules and the enzyme polyphenoloxidase as ingredients
      for the oxidative generation of flavonol-protein conjugates during the extraction
      process. In the present work this is illustrated by spectroscopic analyses of the
      free and bound flavonoids in Parietaria pollen extracts, as well as of the
      peptide fragments produced from the allergenic proteins by enzymatic or chemical
      hydrolysis. None of these relatively harsh treatments had a significant effect on
      the IgE-binding properties of the allergenic (sub-)components, even though
      detectable proteins in isoelectric focusing and immunoblotting were lost. It is
      proposed that the extraordinary stability of IgE-binding Parietaria components
      over a wide molecular range may be attributed to chromophoric flavonoid side
      chains as (parts of) the corresponding B-cell epitopes.

PMID- 9171889
TI  - In vitro expression of the beta subunit of human complement component C8.
AB  - Human C8 is one of five components of the cytolytic C5b-9 complex of complement.
      It is an oligomeric protein composed of three subunits (alpha, beta, gamma)
      encoded in separate genes. These are arranged as a disulfide-linked alpha-gamma
      dimer and a noncovalently associated beta chain. Biosynthesis studies and
      analyses of humans with hereditary C8 deficiencies suggest that C8 alpha-gamma
      synthesis and secretion can occur independently of C8 beta, but that serum levels
      of C8 beta are dependent on C8 alpha-gamma. One aim of the present study was to
      determine if functional human C8 beta could be synthesized in the absence of C8
      alpha-gamma. Human C8 beta expression constructs were prepared and used to
      produce recombinant C8 beta (rC8 beta) in insect and COS-7 cells. Both cell types
      secreted rC8 beta that was similar in size to human C8 beta and exhibited similar
      ability to associate with human C8 alpha-gamma and form functional C8. A mutant
      form of C8 beta in which N-glycosylation sites were eliminated was also expressed
      and found to be functionally similar to rC8 beta and human C8 beta. These results
      indicate that C8 alpha-gamma is not required for intracellular processing and
      secretion of C8 beta. Furthermore, N-linked carbohydrate on C8 beta is not
      necessary for association with C8 alpha-gamma or for C8 activity.

PMID- 9171890
TI  - Design and expression of a stable bispecific scFv dimer with affinity for both
      glycophorin and N9 neuraminidase.
AB  - We have designed and produced a stable bispecific scFv dimer (bisFv) by non
      covalent association of two hybrid VH-VL pairs derived from an anti-neuraminidase
      antibody (NC10) and an anti-glycophorin antibody (1C3). The bisFv dimer was
      demonstrated to have binding activity to the two respective target antigens and
      was evaluated as a reagent for rapid whole blood agglutination assays. The bisFv
      was expressed in the periplasm of Escherichia coli, from a secretion vector which
      comprised two cistrons in tandem under the control of a single lac promoter,
      inducible with IPTG. Each cistron encoded one of the hybrid VH-VL pairs, with V
      domains separated by a linker region encoding the five amino acids, Gly4Ser. The
      short linker region was designed to prevent association of VH and VL regions of
      the same molecule and favour the formation of dimers. The protein synthesized
      from each hybrid scFv cistron was directed to the E. coli periplasm by the
      inclusion of distinctive signal secretion sequences preceding each hybrid gene;
      from pel B of Erwinia cartovora and from gene III of fd phage. The bisFv was
      affinity-purified from culture supernatants via the C-terminal tag epitope FLAG
      and was shown, by FPLC on a Superose 6 column, to be consistent in size with that
      of a scFv dimer. The bisFv was stable for more than 4 months at 4 degrees C and
      was shown by BIAcore analysis to bind to either target antigen, human
      glycophorin, or tern N9 neuraminidase. Simultaneous binding to both target
      antigens was demonstrated when a pre-formed bisFv-neuraminidase complex was shown
      to bind to immobilized glycophorin. In whole blood agglutination assays, the
      bisFv dimer was able to agglutinate red blood cells when crosslinked with an anti
      idiotype antibody (3-2G12) binding to the NC10 combining site, but no
      agglutination occurred on binding the antigen neuraminidase. These results are a
      function of the topology of the epitopes on neuraminidase and have implications
      for the use of relatively rigid bifunctional molecules (as bisFv dimers) to cross
      link two large membrane-anchored moieties, in this case, red blood cell
      glycophorin and neuraminidase, an M(r) 190,000 tetramer.

PMID- 9171891
TI  - Rabbit DQ52 and DH gene expression in early B-cell development.
AB  - Rabbits predominantly rearrange the most 3'VH gene (VH1); thus combinatorial
      diversity is very limited. In man and mouse, the most 3'DH gene, DQ52, is
      preferentially rearranged early in B-cell development. To test whether this
      preference for rearranging a DH gene segment based on 3' end proximity exists in
      rabbit, we cloned and sequenced the rabbit DQ52 gene. The 11 base pair coding
      region sequence is identical to a published mouse DQ52, and 81.8% similar to the
      human sequence. It is localized approximately 805 bp upstream of the JH1 gene.
      However, the 3' recombination signal sequence has an atypical nonamer. We
      prepared mRNA from 15- to 28-day fetal rabbits and amplified expressed VDJ
      sequences of mu mRNA by RT-PCR. The PCR products with VDJ rearrangements were
      cloned and sequenced. As expected, 44 of 45 VDJ sequences reflected use of the 3'
      VH1a2 gene, but the DQ52 gene was utilized very infrequently, if at all. We found
      only one VDJ sequence from 28-day fetal liver B-cells with 8 bp that matched the
      germline DQ52 sequence. Instead of expressing DQ52, another DH gene, Df was
      frequently expressed. We cloned the genomic Df gene and localized it about 32 kb
      upstream of the JH region. Thus, in contrast to man and mouse, rabbits
      preferentially express a DH gene located in the middle of the DH region early in
      B cell ontogeny. This may correlate with more frequent initial rearrangement of
      VH to DH in rabbit B cells.

PMID- 9171892
TI  - Role of non-anchor residues of Db-restricted peptides in class I binding and TCR
      triggering.
AB  - To understand better, the role of non-anchor residues of class I restricted T
      cell epitopes in class I binding and TCR stimulation, a panel of peptides was
      synthesized in which each of the non-anchor positions of the Db-restricted
      influenza peptide, ASNENMETM, was changed to each of the 20 natural amino acids
      (AAs). The relative affinity of all the peptides for Db was determined and their
      ability to stimulate anti-ASNENMETM cytotoxic T cell hybridomas was also
      assessed. The results illustrated that for Db binding, the AAs with the most
      solvent exposure had the smallest effect on binding. Changes at other positions
      affected binding to different degrees. Results for the recognition by the T cell
      hybridomas indicated that a peptide-MHC complex represents a multitude of
      epitopes, as each hybridoma recognized a different subset of peptides. Most
      changes in the highly solvent-exposed residues negatively affected recognition by
      all hybridomas while changes in other positions affected each hybridoma
      differently, independent of the direction of the side chain of the AA at that
      position. Furthermore, the use of saturating concentrations of low and high
      binding peptides showed that, as long as the class I-peptide complex is formed,
      the T-cell receptor does not differentiate between high and low binding peptides.
      This indicates that, although the stability of the class I-peptide complex is
      highly dependent on peptide affinity, the class I MHC conformation induced by low
      affinity peptides does not necessarily differ significantly from that induced by
      high affinity peptides. The results of peptide-class I recognition by one
      ASNENMETM-specific hybridoma was used to construct a peptide that differed from
      ASNENMETM at four of the nine residues, yet stimulated the hybridoma to a level
      comparable to ASNENMETM. In addition, peptides bearing the canonical Db-binding
      motif but unable to bind to the class I molecule with high affinity could be made
      to bind Db, by changing unfavorable AAs to favourable ones at appropriate
      positions. The extended motif determined was used to identify more accurately the
      peptides derived from Coxsakie b3 virus that would bind Db. It was also shown
      that some of the canonical characteristics of the peptide motif could be obviated
      and still obtain high affinity binding, provided optimal AAs, were present at
      secondary anchor positions.

PMID- 9171893
TI  - Direct evidence that gamma 1 and gamma 3 switching in human B cells is
      interleukin-10 dependent.
AB  - Interleukin-10 (IL-10) has various effects on B cell immunoglobulin (Ig)
      production. Indirect evidence suggests that IL-10 functions as a switch factor
      for IgG production. In this study, the switch deleted Ig gene DNA was isolated
      and characterized, as direct evidence that IL-10 induced isotype switching in
      human B cells. In addition, 16 chimeric Ig fragments were isolated, representing
      deleted DNA generated by in vitro isotype switching from mu to gamma in human B
      cells, following stimulation with IL-10 and anti-CD40 monoclonal antibodies (CD40
      mAb). These clones consisted solely of S gamma 1/S mu and S gamma 3/S mu chimeric
      switch circular DNAs, no S gamma 2/S mu or S gamma 4/S mu switch DNA was
      observed. In addition, IL-10 alone induced only gamma 1 and gamma 3 germ-line
      mRNA transcripts, as determined by restriction digestion of the reverse
      transcription-polymerase chain reaction products. Three modes of mu-gamma 3
      isotype switching were detected: (1) direct switching; (2) internal deletion of S
      mu proceeding mu to gamma 3 switching; and (3) internal deletion of S gamma 3
      proceeding mu to gamma 3 switching. These results directly demonstrate that gamma
      1 and gamma 3 switching in human B cells is specifically induced by IL-10 in the
      presence of CD40 mAb.

PMID- 9171894
TI  - Modulating the immunological properties of a linear B-cell epitope by insertion
      into permissive sites of the MalE protein.
AB  - In a previous study, a set of positions in the MalE protein from Escherichia coli
      were identified, which tolerated short insertions or deletions without
      compromising the maltose binding activity of the protein. It is now shown that
      these sites accommodate an insert of 13 amino acids and are, therefore,
      permissive. Eleven sites were used, including eight permissive sites, to display
      a linear neutralization B-cell epitope of poliovirus (C3 epitope) at different
      positions on the surface of MalE. The affinity of a monoclonal neutralizing anti
      poliovirus antibody (anti-C3 mAb) for the hybrid proteins varied from
      undetectable, to more than 1000 times higher than for the synthetic peptide.
      Therefore, some MalEC3 proteins mimic interactions of the viral epitope with the
      monoclonal antibody more efficiently than the free peptide. The results are
      interpreted in terms of the mobility of the insert and its flanking regions. It
      was further shown that some of the purified hybrid proteins are able to induce
      high titer anti-C3-peptide antibodies in mice. A strong correlation exists
      between the capacity of a MalEC3 protein to induce anti-C3-peptide antibodies and
      the antigenicity of the inserted peptide, measured with a polyclonal serum raised
      against the synthetic peptide.

PMID- 9171895
TI  - V lambda-light chain genes reconstitute immune responses to defined carbohydrate
      antigens or haptens by utilizing different VH genes.
AB  - The contribution of the lambda-light chain to the development of peripheral B
      cell repertoire and generation of specific antibodies to haptens and
      polysaccharide antigens was studied in genetically manipulated kappa-deficient
      and lambda 2-transgenic mice. The results clearly demonstrate a non
      stoichiometric VH gene family expression in the absence of k-light chain and
      suggest a non-stochastic pairing between VH and V lambda genes, expressed in the
      peripheral B cell repertoire. A shift in VH gene utilization in the case of VI
      lambda + antibodies was evident in response to beta 2-6 fructosan and TNP hapten.
      These observations demonstrate the availability of compensatory mechanisms in the
      absence of VK genes and are consistent with the hypothesis that VH gene family
      expression is controlled by genetic factors from inside the VH locus.
      Furthermore, genetic factors from outside the VH locus, namely restricted
      available light chain diversity, may lead to a shift in VH gene utilization in
      the peripheral B cell repertoire.

PMID- 9171896
TI  - VH repertoire in human B lymphocytes stimulated by CD40 ligand and IL-4: evidence
      for positive and negative selection mechanisms coupled to CD40 activation.
AB  - In the normal immune system, B cells are thought to be negatively or positively
      selected at various checkpoints during their maturation; a process that maintains
      a broad immunoglobulin repertoire while eliminating non-functional or potentially
      harmful autoreactive antibodies. This study tested the hypothesis that
      utilization of certain immunoglobulin heavy chain variable region (VH) genes,
      possibly as a consequence of intrinsic affinity for various ligands, directs
      positive or negative B cell selection coupled to B cell activation in the
      periphery during the immune response. The specific prediction that the VH
      repertoire of CD40-activated B cells would differ from the repertoire of
      unstimulated cells from the same donor, was tested by assessing VH utilization
      among human B cell clones grown in vitro, following stimulation with CD40 ligand
      (CD40L) and IL-4. The results showed that, although utilization of the known VH
      families and of individual VH3 genes was similar to that found in unstimulated B
      lymphocytes of the same donor, utilization of individual VH4 genes in CD40
      activated B cells displayed a pattern that was markedly different from that of
      the unstimulated B cells. An allele of V4-61, V4-61b, was over-represented among
      the activated cells and, in contrast, the V4-34 gene (known to encode cold
      agglutinins with strong autoreactive properties) was modestly represented among
      the VH4 activated B cells, although V4-34 was overwhelmingly predominant in the
      repertoire of resting B cells. These results point to the existence of selection
      mechanisms that operate during B cell activation in the periphery. These
      mechanisms may favor B cells utilizing certain VH genes and disfavor the cells
      that utilize other genes, possibly because utilization of the latter confers
      autoreactivity.

PMID- 9171897
TI  - Low molecular weight antigen arrays delete high affinity memory B cells without
      affecting specific T-cell help.
AB  - An ongoing, T-cell dependent, secondary antibody response to an epitope can be
      suppressed in vivo by low molecular weight, soluble polymers, bearing multiple
      copies of the same epitope. This study illustrates that such suppressive T-cell
      independent antigen arrays target the epitope-specific, high affinity, memory B
      cells for long-term functional elimination. Splenocytes from hyperimmune
      unsuppressed donors, when adoptively transferred into irradiated recipients will
      readily reconstitute a secondary anti-hapten response after antigenic challenge.
      No such response was observed with splenocytes transferred from hyperimmune
      donors suppressed with antigen arrays. The extent of suppression depended on
      antigen array dose and duration of exposure in the donor animals. The suppressive
      antigen array carryover from the donors into the recipients was negligible and
      insufficient to account for the observed suppression. B cells from hyperimmune
      mice producing high affinity anti-fluorescein antibodies, generated by multiple
      fluoresceinated ovalbumin (FL-OVA) injections, were helped efficiently by T cells
      from hyperimmune donors, which were either unsuppressed or suppressed with
      antigen arrays. Accordingly, help from T cells, specific for the carrier protein
      remains intact after such suppression. Neither lipopolysaccharide (LPS), nor
      additional transferred carrier-primed T cells could reverse the unresponsiveness
      of adoptively transferred splenocytes from suppressed animals. Flow cytometry
      showed that the number of hapten-specific B cells was markedly reduced after
      suppression. Collectively, these data show that the long term elimination of an
      ongoing T-cell dependent antibody response by suppressive exogenous antigen
      arrays is due to the functional deletion of high affinity, antigen-specific B
      cells, even in the presence of adequate T-cell help. The long-term nature of such
      functional deletion strongly suggests physical deletion of the antigen-specific B
      cell population.

PMID- 9171898
TI  - Inhibition of complement activity by humanized anti-C5 antibody and single-chain
      Fv.
AB  - Activation of the complement system contributes significantly to the pathogenesis
      of numerous acute and chronic diseases. Recently, a monoclonal antibody (5G1.1)
      that recognizes the human complement protein C5, has been shown to effectively
      block C5 cleavage, thereby preventing the generation of the pro-inflammatory
      complement components C5a and C5b-9. Humanized 5G1.1 antibody, Fab and scFv
      molecules have been produced by grafting the complementarity determining regions
      of 5G1.1 on to human framework regions. Competitive ELISA analysis indicated that
      no framework changes were required in the humanized variable regions for
      retention of high affinity binding to C5, even at framework positions predicted
      by computer modeling to influence CDR canonical structure. The humanized Fab and
      scFv molecules blocked complement-mediated lysis of chicken erythrocytes and
      porcine aortic endothelial cells in a dose-dependent fashion, with complete
      complement inhibition occurring at a three-fold molar excess, relative to the
      human C5 concentration. In contrast to a previously characterized anti-C5 scFv
      molecule, the humanized h5G1.1 scFv also effectively blocked C5a generation.
      Finally, an intact humanized h5G1.1 antibody blocked human complement lytic
      activity at concentrations identical to the original murine monoclonal antibody.
      These results demonstrate that humanized h5G1.1 and its recombinant derivatives
      retain both the affinity and blocking functions of the murine 5G1.1 antibody, and
      suggest that these molecules may serve as potent inhibitors of complement
      mediated pathology in human inflammatory diseases.

PMID- 9171899
TI  - Electrochemical and histomorphometric evaluation of the TiNiCu shape memory
      alloy.
AB  - By means of electrochemical and quantitative histomorphometric methods, the
      corrosion resistance and tissue biocompatibility of Ti50Ni50 and Ti50Ni50-xCux (x
      = 1, 2, 4, 6, 8) were investigated. It is discovered that the repassivation
      potential of Ti50Ni50-xCux (x = 2, 4, 6, 8) alloys is about 200 mV higher than
      that of Ti50Ni50 alloy. Namely, the addition of Cu raises the repassivation
      potential of TiNi shape memory alloys and improves their corrosion resistance.
      Pitting potentials of Ti50Ni50 and Ti50Ni50-xCux (x = 1, 2, 4, 6, 8) alloys
      increase with solution pH value, but the repassivation potentials keep constant.
      The adding of Cu has no obvious influence on pitting potential (Epit) of TiNi
      alloys, meanwhile, the corrosion potential and corrosion rate of Ti50Ni50-xCux (x
      = 1, 2, 4, 6, 8) alloys are irrelevant to its Cu content and the values are
      almost the same as those of TiNi alloys. The connective tissue layer covering the
      plates is statistically significantly thicker for Ti50Ni42Cu8 plates (p < 0.05)
      than that of Ti50Ni50, Ti50Ni48Cu2, Ti50Ni44Cu6 plates after one month. The
      numbers of connective tissue cells, polynucleated cells, macrophages and round
      cells are higher for Ti50Ni42Cu8 plates than those of the other three types of
      plates, but no statistically significant differences are detected. There are no
      significant differences on tissue reaction parameters after two and three months
      among four alloys. After one, two and three months implantation, no corrosion is
      observed on the plates surfaces. A preliminary conclusion can be drawn that
      Ti50Ni50-xCux (x = 2, 6, 8) shape memory alloys have good biocompatibility.

PMID- 9171900
TI  - Titanium-porcelain system. Part II: Bond strength of fired porcelain on nitrided
      pure titanium.
AB  - Commercially pure titanium (CPT) substrate was subjected to porcelain firing and
      bond strengths under three-point bending mode (span length: 15 mm; crosshead
      speed: 0.5 mm/min) were evaluated. Experimental variables included surface
      treatments of CPT and porcelain firing schedules. Variables for the surface
      treatments were (1) sandblasting, (2) mono- and triple-layered nitridation, and
      (3) mono-layered chrome-doped nitridation. Variables for the porcelain firing
      schedule included (4) bonding agent application, (5) bonding agent plus gold
      bonding agent application, and (6) Procera porcelain application. All together
      eleven sample groups were prepared with different combination of aforementioned
      experimental variables. Statistically all of them exhibited no significant
      differences. Hence, we employed two further criteria; (I) the minimum bond
      strength should exceed the maximum porcelain strength per se, and (II) the CPT
      substrate should not be heated close to the beta-transus temperature. After
      applying these criteria, it was concluded that mono-layered nitridation and mono
      layered application of chrome-doped nitridation on both (with and without)
      sandblasted and non-sandblasted surfaces were the most promising conditions for a
      successful Titanium-Porcelain System.

PMID- 9171902
TI  - Viable bone formation in porous hydroxyapatite: marrow cell-derived in vitro bone
      on the surface of ceramics.
AB  - With the aim of in vitro production of bone fragments more closely resembling
      autogenous bone, rat cultured bone marrow cells were combined with porous
      hydroxyapatite (HA) discs and cultured in the presence of dexamethasone (Dex).
      Bone marrow cells were collected from the femoral diaphyses of a 7-week-old male
      Wistar rat, and primary culture was performed for six days. Then, cell
      suspensions were prepared by trypsin treatment, and combined with the porous HA
      discs. After a 2-hour incubation, the composites were additionally cultured for
      up to 4 weeks (subculture) in the presence of Dex. In a control group, the
      subculture was performed without Dex. After 1, 2, 3 and 4 weeks of subculturing,
      the HA discs were removed, and alkaline phosphatase (ALP) activity, bone Gla
      protein (BGP), and DNA were quantitated. A portion of the disc was prepared for
      scanning electron microscopy (SEM), from which bone formation was evaluated
      morphologically. ALP activity peaked at 2-3 weeks and decreased at 4 weeks. BGP
      levels began to increase at 3 weeks. In the SEM study, mineralized collagenous
      extracellular matrix was noted at 3 and 4 weeks. In the control group, neither
      significant ALP activity nor increased BGP was detected. These biochemical and
      morphological results suggest that with the culture technique, active bone
      formation in the pore regions of HA can be fabricated in vitro. It is anticipated
      that when composites are subcultured in this way they will function as a bone
      graft with properties similar to those of autogenous bone.

PMID- 9171901
TI  - Effect of crosslinked poly(1-vinyl-2-pyrrolidinone) gels on cell growth in static
      cell cultures.
AB  - Poly(1-vinyl-2-pyrrolidinone) (PVP) and copolymers of 1-vinyl-2-pyrrolidinone are
      insoluble in water when crosslinked but they can absorb very large amounts of
      water to become syringe-injectable hydrogels. Such gels have been investigated
      recently as potential substitutes for the vitreous humour in the eye. In this
      study, during the cytotoxic evaluation by sulforhodamine B colorimetric assay of
      variously crosslinked PVP gels, it was found that many of them showed
      protective/growth promoting effects on 3T3 mouse fibroblasts in static cultures,
      a phenomenon encountered previously only with aqueous solutions of a limited
      number of natural or synthetic polymers. Particularly, the gels crosslinked with
      diethylene glycol dimethacrylate (DEGDMA) induced a significant enhancement of
      cell proliferation, especially in serum-free cultures. No correlation between
      this effect and the essential gel properties (chemical composition,
      viscoelasticity and equilibrium water content) could be established. The study
      demonstrated that crosslinked PVP hydrogels showed a serum-like growth promoting
      effect on an anchorage-dependent cell line, which may be due to physical
      protection, inability of the insoluble gels to penetrate cell membranes, and
      their ability to mimic the extracellular matrix.

PMID- 9171903
TI  - A study of the combined effects of shelf ageing following irradiation in air and
      counterface roughness on the wear of UHMWPE.
AB  - Damage to polished femoral heads in vivo can cause increased wear of acetabular
      cups. Oxidation and ageing after sterilisation by gamma irradiation in air, can
      also change the mechanical properties and wear resistance of ultra high molecular
      weight polyethylene (UHMWPE). This study investigated the combined effect of
      these changes in material properties on the wear of UHMWPE for different
      counterface roughnesses, representative of new femoral heads and those damaged in
      vivo. Wear rates were studied on a tri-pin-on-disc tribometer in a protein
      containing solution. A comparison was made of the wear, using three different
      counterface roughnesses, of specimens that were manufactured from polyethylene
      acetabular cups of different shelf ages (3-120 months) after gamma irradiation in
      air but never implanted. These were compared to the wear of control specimens
      that were manufactured from cups that had not been sterilised. The wear surfaces
      were tested 1 mm below the initial articulating surface of the cup, the position
      of high degradation. The wear rate of UHMWPE which had been sterilised by gamma
      irradiation in air was shown to increase significantly with ageing time on the
      shelf for all counterface conditions. The wear rate of all materials increased
      markedly as the counterface roughness increased, but to different extents
      depending on the age of the material. The combined effect of ageing and increase
      in counterface roughness had a dramatic effect (as high as 2000 fold increase) on
      the wear rate. Both ageing of the polymer and damage to the femoral head have
      been cited as causing increased wear in vivo. The results of this study
      demonstrate that these variables can act synergistically to markedly effect
      UHMWPE wear rate.

PMID- 9171904
TI  - Preparation and characterization of double layered coating composed of
      hydroxyapatite and perovskite by thermal decomposition.
AB  - A new modified thermal decomposition method is described for preparing a double
      layered coating on titanium plates which includes an initial perovskite (CaTiO3)
      layer followed by a hydroxyapatite (HA) layer on top. The characterization of the
      coating was studied by X-ray diffractometry and infrared spectroscopy and
      indicated that the double layer consisted of carbonate HA and CaTiO3 and the
      thickness of the layer was 4 microns. The coating was performed on the inner
      surfaces of 50-200 microns sized pores and was also consistent in the smallest of
      the pores even those of 50 microns. Bone formation was examined in canines at 2
      32 week intervals and was dominant on coated plates and in large-sized pores
      before 16 weeks. However, after 16 weeks bone ingrowth was similar in non-coated
      and coated plates and in all pore sizes. The results indicated that HA could only
      influence early bone ingrowth, though good bone ingrowth into small pores
      indicated that HA exhibited enhanced osteocompatibility. Our methodology ensured
      the stability of the HA layer consequently minimizing the problems associated
      with HA loss.

PMID- 9171905
TI  - Normal pituitary response to metyrapone in the morning in depressed patients:
      implications for circadian regulation of corticotropin-releasing hormone
      secretion.
AB  - Excess secretion of cortisol in depressed patients has been documented by a
      number of investigators, which is presumed secondary to increased corticotropin
      (ACTH) and ACTH-releasing hormone (CRH) secretion. To unmask the proposed
      increased central (CRH) drive, we administered metyrapone in the AM to 13
      depressed and 13 age- and sex-matched normal control subjects. Metyrapone
      administration resulted in a prompt decrease in plasma cortisol and in an
      increase in 11-deoxycortisol, the inactive precursor, in all subjects. Both
      depressed patients and normal control subjects demonstrated clear increases in
      ACTH and beta-lipotropin/beta-endorphin production. There were no significant
      differences between patients and controls in any hormonal measures following
      metyrapone administration. These data suggest that: 1) in the absence of negative
      feedback (cortisol blockade), mildly to moderately depressed outpatients do not
      manifest increased central drive in the morning; and 2) the secretory capacity of
      the corticotropes do not differ between such depressed patients and controls.

PMID- 9171906
TI  - Serotonin transporter binding sites and mRNA levels in depressed persons
      committing suicide.
AB  - The serotonin transporter (5-HTT) has been found altered in postmortem brain
      samples from persons committing suicide, but the results of radioligand binding
      studies have been inconsistent. In the present series of experiments,
      autoradiographic radioligand binding and in situ hybridization techniques were
      utilized to examine 5-HTT function in the brains of 8 depressed subjects who had
      committed suicide, and matched controls. It was hypothesized that depressed
      subjects would demonstrate decreased numbers of 5-HTT binding sites and mRNA;
      however, [125I]RTI-55 binding to the 5-HTT was not different in the midbrain,
      hippocampus, or frontal cortex of depressed subjects. Also, 5-HTT mRNA levels in
      dorsal and median raphe nuclei were not different between controls and depressed
      subjects. The current results, although limited in scope because of the small
      number of subjects included, offer no evidence that alterations in the 5-HTT
      occur in pertinent brain regions of depressed individuals.

PMID- 9171908
TI  - Long-term food restriction down-regulates the density of serotonin transporters
      in the rat frontal cortex.
AB  - The influence of feeding rats only half the amount of their normal daily intake
      of a complete rat chow on the affinity and the density of serotonin (5-HT)
      transporters was measured in membrane preparations of the frontal cortex and the
      midbrain by a [3H]paroxetine binding assay. In young rats (10 weeks), a
      significant reduction of about 30% of the Bmax values of [3H]paroxetine binding
      occurred in the frontal cortex after 1 and 2 weeks of restricted food intake. No
      starvation-induced decline of the density of 5-HT transporters was seen in the
      midbrain. When older rats (50 weeks) were subjected to the same 50% reduction of
      daily food intake for 2 weeks, no such down-regulation of the density of cortical
      5-HT transporters was observed. The affinity of the 5-HT transporters, as
      indicated by the unchanged Kd values of [3H]paroxetine binding, was not affected
      by semistarvation in both regions and at both ages. The observed decline of
      [3H]paroxetine binding sites in the frontal cortex of young adult rats is the
      first demonstration of long-term regulatory phenomena of brain 5-HT transporters
      triggered by a physiologic stimulus.

PMID- 9171907
TI  - Inducing lifestyle regularity in recovering bipolar disorder patients: results
      from the maintenance therapies in bipolar disorder protocol.
AB  - On the basis of theories we articulated in earlier papers (Ehlers et al 1988:
      Arch Gen Psychiatry 45:948-952, 1993: Depression 1:285-293), we have developed an
      adjunctive psychosocial intervention for patients with bipolar 1 disorder.
      Central to this intervention is the establishment of regularity in daily
      routines. In this report, we present data from a controlled investigation
      comparing this new treatment, interpersonal and social rhythm therapy (IPSRT),
      with a conventional medication clinic approach. Despite comparable changes in
      symptomatology over a treatment period lasting up to 52 weeks, subjects assigned
      to IPSRT (n = 18) show significantly greater stability (p = .047) of daily
      routines with increasing time in treatment, while subjects assigned to the
      medication clinic condition (n = 20) show essentially no change in their social
      routines as measured by Social Rhythm Metric (SRM-Monk et al 1990: J Nerv Ment
      Dis 178(2):120-126) score. We conclude that IPSRT is capable of influencing
      lifestyle regularity in patients with bipolar 1 disorder, with the possible
      benefit of protection against future affective episodes.

PMID- 9171910
TI  - Impaired attention-dependent augmentation of MMN in nonparanoid vs paranoid
      schizophrenic patients: a comparison with obsessive-compulsive disorder and
      healthy subjects.
AB  - Mismatch negativity (MMN), in the deviant-minus-standard event-related potential
      (ERP) difference-waveform, may represent a working memory trace of the tone
      difference. Most but not all studies find MMN reduced in schizophrenic patients.
      This report investigates if differences may be attributable to experimental
      condition (diffuse vs focused attention), component identification (N1-like vs N2
      like), topographic distribution, and clinical condition (with/without paranoid
      hallucinatory symptoms, PH/NP). Comparisons were made for 12 PH, 12 NP
      schizophrenic patients with 13 obsessive compulsive and 25 normal control
      subjects. Frontal MMN reduction in schizophrenics largely resulted from an
      absence of an increase in focused attention conditions as in comparison groups.
      But there was a marked temporal activity locus in NP patients. These features
      were not reflected in other components except for a visible but nonsignificant N1
      like temporal locus in NP patients. Further, schizophrenic patients did not show
      an increase in late positivity with focused attention like the comparison groups.
      The results show that so-called automatic processing deficits (amount and locus
      of MMN) are best seen in situations requiring the activation of controlled
      attentional processes. It is suggested that impaired processing of irrelevant
      stimuli and reduced frontal MMN in NP patients may reflect reduced dopaminergic
      responsivity.

PMID- 9171909
TI  - Auditory-evoked potentials as indicator of brain serotonergic activity--first
      evidence in behaving cats.
AB  - Due to the increasing importance of the central serotonergic neurotransmission
      for pathogenetic concepts and as a target of pharmacotherapeutic interventions in
      psychiatry, reliable indicators of this system are needed. Several findings from
      basic and clinical research suggest that the stimulus intensity dependence of
      auditory evoked potentials (AEP) may be such an indicator of behaviorally
      relevant aspects of serotonergic activity (Hegerl and Juckel 1993, Biol
      Psychiatry 33:173-187). In order to study this relationship more directly,
      epidural recordings over the primary and secondary auditory cortex were conducted
      in chronically implanted cats under intravenous (i.v.) administration of drugs
      influencing the serotonergic and other modulatory systems (8-OH-DPAT, m-CPP,
      ketanserin, DOI, apomorphine, atropine, clonidine). The intensity dependence of
      the cat AEP component with the highest functional similarity to this of the N1/P2
      component in humans was significantly changed by influencing 5-HT1a and 5-HT2
      receptors, but not 5-HT1c receptors. This serotonergic modulation of the
      intensity dependence was only found for the primary auditory cortex which
      corresponds to the known different innervation of the primary and secondary
      auditory cortex by serotonergic fibers. Our study supports the idea that the
      intensity dependence of AEP could be a valuable indicator of brain serotonergic
      activity; however, this indicator seems to be of relative specificity because at
      least cholinergic effects on the intensity dependence were also observed.

PMID- 9171911
TI  - A psychophysiological study of the development of delirium in coronary care
      units.
AB  - This is a longitudinal investigation of the psychophysiological mechanism for the
      development of delirium in coronary care units (CCUs). Ten patients satisfying
      DSM-III-R diagnostic criteria for delirium (group D) and 10 controls (group C)
      were drawn from patients admitted to CCU. Electroencephalogram (EEG) and eye
      movement recordings were observed over the days that patients were admitted to
      CCU and on a control day of admission and compared for each group and between
      each day. In the D group, slowing of background EEG activity, particularly on day
      2, and many R (rapid) group eye movements and RS type (rapid superimposed on
      slow) eye movements, particularly on day 3, were observed. That is, from days 2
      to 3, EEG findings showed an improvement in consciousness, and eye movement
      recordings manifested signs of anxiety and tension. These psychophysiological
      findings can be used to explain the transition from prodromal delirium to obvious
      delirium, and are supported by clinical features.

PMID- 9171912
TI  - Fluoxetine-induced Raynaud's phenomenon.

PMID- 9171913
TI  - Neuroleptic malignant syndrome with gangliosidosis type II.

PMID- 9171914
TI  - Effects of lithium on steroid-induced depression.

PMID- 9171915
TI  - Superoxide production by the mitochondrial respiratory chain.

PMID- 9171916
TI  - The physiological significance of mitochondrial proton leak in animal cells and
      tissues.
AB  - Mitochondrial proton leak is an important component of cellular metabolism in
      animals and may account for as much as one quarter to one third of the Standard
      Metabolic Rate of the rat. The activity of the proton leak pathway is different
      in a wide range of animal species and in different thyroid states. Such
      differences imply some function for proton leak and candidates for this function
      include thermogenesis, protection against reactive oxygen species, endowment of
      metabolic sensitivity and maintenance of carbon fluxes.

PMID- 9171917
TI  - Hyperthyroidism and mitochondrial uncoupling.
AB  - During the past years many efforts have been made to elucidate the origin of the
      uncoupling mechanisms induced by hyperthyroidism in mitochondria. Two main
      mechanisms have been proposed: a classical protonophoric uncoupler mechanism,
      considering the action of thyroid hormones at the level of the lipid membrane
      bilayer, and a slipping mechanism with more localized effects at the level of the
      redox proton pumps. This short review is devoted to comparing and discussing the
      evidence against and in favour of these two mechanisms.

PMID- 9171918
TI  - A possible role of slips in cytochrome C oxidase in the antioxygen defense system
      of the cell.
AB  - Evidence is available showing that the coupling efficiency of the proton pump in
      cytochrome c oxidase of mitochondria can under certain conditions decrease
      significantly below the maximum attainable value. The view is developed that
      slips in the proton pump of cytochrome c oxidase represent an intrinsic switch
      mechanism which regulates the relative contribution of energy transfer and
      respiratory protection against oxygen toxicity by the oxidase.

PMID- 9171919
TI  - Superoxide-driven aconitase FE-S center cycling.
AB  - O2- produced by the autoxidation of respiratory chain electron carriers, and
      other cellular reductants, inactivates bacterial and mammalian iron-sulfur
      containing (de)hydratases including the citric acid cycle enzyme aconitase.
      Release of the solvent-exposed iron atom and oxidation of the [4Fe-4S]2+ cluster
      accompanies loss of catalytic activity. Rapid reactivation is achieved by iron
      sulfur cluster reduction and Fe2+ insertion. Inactivation-reactivation is a
      dynamic and cyclical process which modulates aconitase and (de)hydratase
      activities in Escherichia coli and mammalian cells. The balance of inactive and
      active aconitase provides a sensitive measure of the changes in steady-state O2-
      levels occurring in living cells and mitochondria under stress conditions.
      Aconitases are also inactivated by other oxidants including O2, H2O2, NO, and
      ONOO- which are associated with inflammation, hyperoxia and other
      pathophysiological conditions. Loss of aconitase activity during oxidant stress
      may impair energy production, and the liberation of reactive iron may further
      enhance oxidative damage. Iron-sulfur center cycling may also serve adaptive
      functions by modulating gene expression or by signaling metabolic quiescence.

PMID- 9171920
TI  - The role of reactive oxygen species in mitochondrial permeability transition.
AB  - We have provided evidence that mitochondrial membrane permeability transition
      induced by inorganic phosphate, uncouplers or prooxidants such as t-butyl
      hydroperoxide and diamide is caused by a Ca(2+)-stimulated production of reactive
      oxygen species (ROS) by the respiratory chain, at the level of the coenzyme Q.
      The ROS attack to membrane protein thiols produces cross-linkage reactions, that
      may open membrane pores upon Ca2+ binding. Studies with submitochondrial
      particles have demonstrated that the binding of Ca2+ to these particles (possibly
      to cardiolipin) induces lipid lateral phase separation detected by electron
      paramagnetic resonance experiments exploying stearic acids spin labels. This
      condition leads to a disorganization of respiratory chain components, favoring
      ROS production and consequent protein and lipid oxidation.

PMID- 9171921
TI  - Reactive oxygen and nitrogen species regulate mitochondrial Ca2+ homeostasis and
      respiration.
AB  - The reduction of molecular oxygen to water provides most of the biologically
      useful energy. However, oxygen reduction is a mixed blessing because incompletely
      reduced oxygen species such as superoxide or peroxides are quite reactive and
      can, when out of control, cause damage. In mitochondria, where most of the oxygen
      utilized by eukaryotic cells is reduced, the dichotomy of oxygen shows itself
      best. Thus, reactive oxygen is a threat to them, as is evident from oxidative
      damage to mitochondrial lipids, proteins, and nucleic acids. Reactive oxygen, in
      the form of peroxides, also serves useful functions in mitochondria. This is
      exemplified by the control of mitochondrial and cellular calcium homeostasis,
      whose understanding has improved greatly during the last few years. An exciting
      new aspect is the discovery that nitric oxide and congeners have an enormous
      impact on mitochondria. Physiological concentrations of nitrogen monoxide (NO) at
      physiological cellular oxygen pressure inhibit cytochrome oxidase and thereby
      respiration. A transient inhibition of cytochrome oxidase by NO appears to be
      used in at least some forms of cell signalling. Peroxynitrite, the product of the
      reaction between superoxide and NO, can stimulate the specific calcium release
      pathway from mitochondria by oxidizing some vicinal thiols in mitochondria. There
      is evidence mounting that mitochondrial calcium handling and its modulation by
      reactive oxygen and nitrogen species is important for necrotic and apoptotic cell
      death.

PMID- 9171922
TI  - Role of the mitochondrial permeability transition pore in apoptosis.
AB  - Mitochondrial permeability transition (PT) involves the formation of proteaceous,
      regulated pores, probably by apposition of inner and outer mitochondrial membrane
      proteins which cooperate to form the mitochondrial megachannel (= mitochondrial
      PT pore). PT has important metabolic consequences, namely the collapse of the
      mitochondrial transmembrane potential, uncoupling of the respiratory chain,
      hyperproduction of superoxide anions, disruption of mitochondrial biogenesis,
      outflow of matrix calcium and glutathione, and release of soluble intermembrane
      proteins. Recent evidence suggests that PT is a critical, rate limiting event of
      apoptosis (programmed cell death): (i) induction of PT suffices to cause
      apoptosis; (ii) one of the immediate consequences of PT, disruption of the
      mitochondrial transmembrane potential (delta psi m), is a constant feature of
      early apoptosis; (iii) prevention of PT impedes the delta psi m collapse as well
      as all other features of apoptosis at the levels of the cytoplasma, the nucleus,
      and the plasma membrane; (iv) PT is modulated by members of the apoptosis
      regulatory bcl-2 gene family. Recent data suggest that the acquisition of the
      apoptotic phenotype, including characteristic changes in nuclear morphology and
      biochemistry (chromatin condensation and DNA fragmentation), depends on the
      action of apoptogenic proteins released from the mitochondrial intermembrane
      space.

PMID- 9171923
TI  - Mechanisms of oxygen taxis in bacteria.
AB  - Since 1881 when Englemann reported aerotaxis in bacteria, an understanding of the
      molecular nature of the signal transduction remains a daring goal for
      microbiologists. This short review discusses known facts and recent advances in
      the field including the discovery of the flavoprotein receptor which drives
      Escherichia coli towards oxygen. Possible mechanisms of oxygen sensing in various
      bacterial species are considered in connection with the existing, often
      fragmental, data on phototaxis, redox taxis and taxis repellent effect of the
      reactive oxygen species (ROS).

PMID- 9171924
TI  - Cu,Zn-superoxide dismutase gene dosage and cell resistance to oxidative stress: a
      review.
AB  - It is well established that superoxide dismutase (SOD) is the irresplaceable
      enzyme for aerobic lifestyle. Our understanding of its role has made strides
      recently as the result of gene transfection approach. Available data on
      consequences of Cu,Zn-SOD gene transfection in cell resistance to oxygen toxicity
      are reviewed. There are data that increasing only Cu,Zn-SOD can be toxic, and the
      balance between Cu,Zn-SOD and peroxide-removing enzymes is supposed to be of
      prime importance in the antioxidant defence. Role of Cu,Zn-SOD deregulation in
      carcinogenesis is discussed.

PMID- 9171925
TI  - Substance abuse, traumatic brain injury and neuropsychological outcome.
AB  - The neuropsychological performance of 119 patients with severe closed traumatic
      brain injury (TBI) who had received toxicology screens at the time of trauma
      centre admission was examined. Three groups were created: normal screen, positive
      alcohol screen, or positive abused drugs screen (with or without the presence of
      alcohol). The admitting Glasgow Coma Scale (GCS) score was significantly lower in
      the positive alcohol screen group than the normal screen group, while the three
      groups did not differ in length of post-traumatic amnesia (PTA) or years of
      education. Neuropsychological assessment was conducted during inpatient
      rehabilitation, following resolution of PTA. Normal screen patients obtained
      significantly better scores than the abused-drugs patients on the Full Scale IQ
      (FIQ) and Verbal IQ (VIQ) indices of the Wechsler Adult Intelligence Scale
      Revised and the Verbal Memory, General Memory, Attention-Concentration, and
      Delayed Recall indices of the Wechsler Memory Scale-Revised. Normal screen
      patients also scored significantly higher than positive alcohol screen patients
      on FIQ and VIQ indices and all five indices from the Wechsler Memory Scale
      Revised. These data suggest the existence of an additive effect of substance
      abuse on neuropsychological outcome in TBI. Findings have potential implications
      for both acute management and rehabilitation of TBI.

PMID- 9171926
TI  - Functional outcome after violence related traumatic brain injury.
AB  - Violent injuries have become an increasingly prevalent cause of traumatic brain
      injury (TBI). These injuries can be classified as either penetrating or non
      penetrating in nature. While much of the research on violence has been within a
      military population, there exists a marked difference between military and
      civilian injuries. Prior work has reported relatively poor outcomes for those
      individuals who have suffered penetrating TBIs, but little has been done to
      assess specific functional outcome parameters in survivors. We examined 25
      subjects that had sustained blunt injuries and 25 cases with penetrating injuries
      as a result of a violent act. Cases were matched by initial Glasgow Coma Scale
      (GCS), age and educational level. Mean GCS for this study sample was 8.8. The
      following outcome variables were assessed at rehabilitation admission and
      discharge and at 1 year post injury: Disability Rating Scale (DRS), Rancho Los
      Amigos Scale (LCFS), Functional Independence Measure (FIM) (ambulation,
      expression items), length of stay, and cost of care. Student's t-tests were
      performed to assess for differences between the two groups. No significant
      differences were noted between the groups for any of the outcome variables.
      Although penetrating injuries may have a higher initial mortality, those who
      survive to come to rehabilitation appear to have similar outcomes to those
      patients with non-penetrating violence related injuries.

PMID- 9171927
TI  - Conversational assessment following traumatic brain injury: a comparison across
      two control groups.
AB  - Although changes in discourse are frequently referred to in the traumatic brain
      injury (TBI) literature, they are difficult to objectify and measure. It is not
      always easy, therefore, for clinicians to differentiate between discourse
      behaviours which may have been present premorbidly, and those which are uniquely
      associated with TBI. The major aim of this study was to systematically examine
      and describe the nature of conversational impairment following severe TBI, with
      particular reference to the premorbid sociolinguistic characteristics of the TBI
      population. A second aim of the study was to examine the relationship between
      discourse impairment following TBI and severity of injury. Twenty-six TBI
      participants were compared with 26 non-brain-injured orthopaedic patients, and 26
      university students, using Damico's Clinical Discourse Analysis (CDA). As
      predicted, global measures derived from the CDA did not differentiate the groups.
      The TBI group was, however, found to differ significantly from both control
      groups on a modified measure (CDA-M) which removes discourse errors that occurred
      with similar frequency across the three groups. Performance on this measure
      correlated significantly with severity of injury. Further, it was found that
      there were quantitative and qualitative differences between two seventy subgroups
      in the TBI group with respect to their CDA-M profiles. While nearly all members
      of the TBI group made errors associated with information transfer, only the more
      fundamental 'rules' of conversational interaction. The results are discussed in
      relation to the psychosocial implications of the findings, together with issues
      in sampling and measuring conversational discourse in the TBI population.

PMID- 9171928
TI  - The experiential impact of head injury on adolescents: individual perspectives on
      long-term outcome.
AB  - Thirty-one young people, who were experiencing chronic sequelae of a head injury
      sustained at least 1 year previously, were interviewed in-depth about the impact
      head injury had had on their lives. Their functioning was also assessed using the
      Offer Self-Image Questionnaire (OSIQ-R). The main theme raised by subjects was
      that they had not received adequate explanation of the emotional problems
      associated with head injury and relevant support in coming to terms with their
      condition. Head injury had had a devastating effect on their lives, causing
      limitations in day-to-day activities, employment, education and relationships,
      and they scored significantly below norms on the OSIQ-R scale of Self-Confidence.
      However, these young people had a predominantly positive attitude towards life,
      which appeared to be related to their appreciation of how fortunate they had been
      to survive. They scored significantly above norms on the OSIQ-R scale of Social
      Functioning. Markers of poor functioning were identified and, in clinical
      practice, could be used as a method of highlighting those head-injured young
      people who potentially are most in need of support. The findings have
      implications for future research directions, service delivery and planning, in
      that particular weaknesses of current provision are demonstrated and
      recommendations made for improvements.

PMID- 9171929
TI  - Heart-rate variability in chronic traumatic brain injury.
AB  - Heart-rate variability (HRV), a measure of fluctuation around the mean heart
      rate, reflects the sympathetic and parasympathetic balance of the autonomic
      nervous system, and is an excellent technique to study cardiovascular tone in
      patients with neurological injuries. The purpose of this study was to determine
      whether abnormal HRV is present in patients with traumatic brain injury (TBI)
      during the post-acute recovery phase. Using a prospective, case/control design,
      we performed 24-h ambulatory ECG monitoring in seven TBI patients and in seven
      controls (C). There was a significant difference in root mean squared successive
      difference of RR intervals (C 40.4 +/- 10.3, TBI 23.3 +/- 16.5, p = 0.04) between
      TBI and C. Four patients with TBI (compared to one control) had abnormal standard
      deviation of the RR interval. When these four patients were compared to their
      matched controls, significant differences were found in frequency domain measure
      (In total power: TBI 4.4 +/- 0.9 ms2, C 7.1 +/- 1.4 ms2, In low frequency: TBI
      3.3 +/- 1.1 ms2, C 6.4 +/- 1.4 ms2; In high frequency TBI 2.0 +/- 1.0 ms2, C 4.8
      +/- 1.3 ms2, all p < 0.05). Thus, abnormalities in both time and frequency
      domains of HRV are present in TBI during the post-acute recovery phase.

PMID- 9171931
TI  - Staff stress in head injury rehabilitation; Brain Injury, 10(10): 779.

PMID- 9171930
TI  - The combined use of amantadine and l-dopa/carbidopa in the treatment of chronic
      brain injury.
AB  - The frontal lobes are particularly vulnerable to injury during trauma. The
      syndrome commonly attributed to frontal lobe dysfunction includes problems with
      impulsivity, perseveration, disinhibition, amotivation, attention, planning, and
      problem solving. These symptoms can respond to certain pharmacologic
      interventions, such as the dopaminergic agents. The case of a 50-year-old woman
      who showed persistent frontal dysfunction 5 years post-injury is described. After
      treatment with amantadine alone, she showed decreased impulsivity and
      perseveration and improved executive function. Further positive response was
      obtained with the addition of l-dopa/carbidopa, with additional improvements in
      constructional praxis, divided auditory attention, and cognitive flexibility. Her
      improved functioning following treatment demonstrates the potential for
      increasing effectiveness through a combination of dopaminergic agents. No side
      effects were observed, and the patient maintained gains at follow-up. The
      rationale for using dopaminergic agents alone and in combination is discussed.

PMID- 9171932
TI  - Use of a comprehensive program of external cueing to chance procedural memory in
      a patient with dense amnesia. Brain Injury, 10(1): 17-25.

PMID- 9171933
TI  - In vitro maintenance and retroviral transduction of human myeloma cells in long
      term marrow cultures.
AB  - One objective of clinical gene marking trials in multiple myeloma (MM) is to
      determine the extent to which relapse after stem cell transplant is attributable
      to contamination of the autograft with myeloma cells. A requirement in these
      studies is ex vivo genetic marking of malignant cells present in autografts which
      are derived from patients exposed to significant prior chemotherapy. We evaluated
      gene marking of cloonogenic myeloma cells in marrow aspirates from 14 patients
      with MM. To effect gene transfer we utilized a long-term marrow culture (LTMC)
      system previously shown to facilitate gene transfer into a spectrum of
      hematopoietic progenitor and stem cells. Transduction of cells in LTMC was
      performed by multiple supernatant exposure. At LTMC initiation and after 21 days
      of culture malignant cells were assessed by morphology, flow cytometry, and
      polymerase chain reaction (PCR). The mean number of day 21 LTMC adherent layer
      derived granulocyte/macrophage progenitors as a percentage of the original
      inoculum was within the normal range for this technique. The efficiency of
      transduction of normal hematopoietic progenitors as determined by the number of
      colonies positive for proviral DNA by PCR, G418 resistance, and X-gal staining
      was also within the expected range; 65%, 44% and 23%, respectively. Thus, there
      was no evidence that prior chemotherapy exposure or malignant cell contamination
      compromised cell survival or gene transfer efficiency in LTMC. All patients
      retained plasma cells in LTMCs for the duration of the 21-day culture period.
      Molecular analysis confirmed the persistence of clonal IgVH gene rearrangements
      in day 21 LTMC-derived DNA from 6 of 12 informative patients (50%). PCR using
      allele-specific primers when available confirmed the specificity of IgVH
      rearrangements for the myeloma clone. In 2 of the 14 patients, expansion of
      clonogenic cells was demonstrated in LTMC. In both cases there was strong
      evidence for transfer of reporter genes (neo and LacZ) into the myeloma clone:
      morphologically abnormal G418-resistant colonies demonstrated intense staining
      for beta-galactosidase, and cytospin preparations showed 100% plasma cells with
      monoclonal heavy and light chain restriction. In one patient, individual colonies
      positive for beta-galactosidase bore a cytogenetic abnormality characteristic of
      the patient's myeloma clone. PCR of DNA from pooled plasma cell colonies using
      tumor-specific CDR3 primers was positive. Our results demonstrate the maintenance
      of myeloma cells in vitro for up to 21 days in LTMC. They further illustrate that
      these cells can be genetically marked using transduction protocols currently
      being tested in clinical trials of hematopoietic cell gene transfer.

PMID- 9171934
TI  - Immune responsiveness to a murine mammary carcinoma modified to express B7-1,
      interleukin-12, or GM-CSF.
AB  - This report characterizes the immunological host response to a syngeneic murine
      mammary carcinoma along with variants genetically modified to express B7-1 or
      secrete GM-CSF and interleukin-12 (IL-12). MT-901 is a subline of a mammary
      adenocarcinoma that was chemically induced in the Balb/c host. It was found to be
      weakly immunogenic by immunization/ challenge experiments, and it induced tumor
      specific T-cell responses in lymph nodes (LN) draining progressive subcutaneous
      tumors. Tumor clones expressing B7-1 or secreting GM-CSF exhibited reduced
      tumorigenicity without completely abrogating tumor growth, whereas IL-12
      elaboration lead to complete tumor growth inhibition. In vivo subcutaneous
      inoculation of a transgenic cell clone secreting GM-CSF (240 ng/10(6) cells/24
      hours) resulted in significantly enhanced T-cell reactivity of tumor-draining
      lymph node (TDLN) cells as compared to wild-type TDLN cells. This finding was
      obtained from observations assessed by several different methods, including: 1)
      in vitro cytotoxicity, 2) in vitro interferon-gamma release, and 3) adoptive
      transfer in mice with established tumor. Moreover, the transfer of activated LN
      cells derived from mice inoculated with GM-CSF-secreting tumor cells resulted in
      the prolonged survival of animals with macroscopic metastatic disease, which was
      not evident utilizing LN cells from mice inoculated with wild-type tumor. By
      contrast, clones that expressed B7-1 or IL-12 (4 ng/10(6) cells/24 hours) did not
      elicit enhanced tumor-reactive TDLN cells compared with wild-type tumor when
      assessed in the adoptive transfer model. The autocrine secretion of GM-CSF by
      transduced tumor cells was found to serve as an effective immune adjuvant in the
      host response to this weakly immunogenic tumor.

PMID- 9171935
TI  - Transmissibility of murine stem cell virus-based retroviral vectors carrying both
      interleukin-12 cDNAs and a third gene: implications for immune gene therapy.
AB  - The combination of immunotherapy with conventional treatments such as radio- and
      chemotherapy may be necessary to eradicate minimal residual disease. Interleukin
      12 (IL-12) is a heterodimeric cytokine composed of two subunits, p40 and p35.
      Coordinate expression of the IL-12 p40 and p35 genes in several solid tumor
      models has been found to induce strong and specific antitumor immune responses.
      In the interest of obtaining high level IL-12 expression in leukemia/lymphoma
      cells for use as vaccines in cancer immunotherapy, we evaluated three IL-12
      retroviral vector designs based on the murine stem cell virus (MSCV) vector which
      efficiently transduces functional genes into normal hematopoietic cells. MSCVpac
      mlL-12 and MIPV-mIL-12 contain an encephalomyocarditis virus internal ribosome
      entry site for internal translation of bicistronic mRNA transcripts, while
      MDCVpac-mIL-12 carries an expression cassette in the U3 region of the 3' long
      terminal repeat. We found that the MSCVpac-mIL-12 vector directed robust
      expression of both p40 and p35 genes in several murine tumor cell lines of
      hematopoietic origin, including a T-cell lymphoma, a B-cell lymphoma, and a
      plasmacytoma/myeloma. In contrast, genomic instability or promoter interference
      hampered p40 gene expression in cells transduced with the MIPV-mIL-12 and MDCVpac
      mIL-12 vectors, respectively. These findings provide the basis for the design of
      IL-12 retroviral vectors for the treatment of hematologic malignancies in humans.

PMID- 9171936
TI  - Evidence for a functional kit receptor in melanoma, breast, and lung carcinoma
      cells.
AB  - We sought to determine the functional significance of the c-kit receptor (Kit) in
      melanoma, breast carcinoma, and non-small cell lung cancer (NSCLC). To explore
      these issues, we first screened cell lines of each type for c-kit mRNA expression
      using a reverse-transcription polymerase chain reaction. We found that WM-39
      melanoma cells, HTB-22 breast carcinoma cells, and A549 NSCLC cells all expressed
      c-kit mRNA. Of interest, all of these cells expressed the c-kit ligand, Steel
      factor (SF). We then assessed the functional significance of c-kit and SF
      expression by disrupting the gene's expression with antisense (AS)
      oligodeoxynucleotides (ODN) targeted to c-kit mRNA codons 1-6 and SF mRNA codons
      2-7, respectively. Nonhybridizing sequences [sense (5) and scrambled (SCR)] were
      also employed as controls. WM-39, HTB-22, and A549 cells were exposed to ODN
      (approximately 25 microM) for 5-7 days. Downregulation of c-kit and SF mRNA, and
      c-kit protein was demonstrated in cells treated with AS ODN. Effects on viable
      cell growth were demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) or 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4 -sulfophenyl)- 2H-tetrazolium (MTS) assay. In fact, c
      kit antisense ODN inhibited the viable cell growth of A549 cells 66% and 79%
      compared to sense and untreated controls (P = .0003; P < .0001). Additionally, WM
      39 cell growth was inhibited 48% and 21% (P < .0001, P < .03) and HTB-22 cell
      growth was inhibited 50% (P < .001) compared to sense and untreated controls.
      Viable cell growth was also significantly inhibited by SF AS ODN compared to S
      and SCR controls in all cell lines. These results demonstrate that WM-39, HTB-22,
      and A549 NSCLC cells all express the c-kit and SF protooncogenes and suggest that
      the encoded receptor and ligand are important for cell growth. By finding the
      presence, and functional importance, of both the receptor and ligand in these
      cells, this study suggests the existence of an autocrine loop growth mechanism
      worthy of further study.

PMID- 9171937
TI  - Gene delivery into malignant cells in vivo by a conjugated adenovirus/DNA
      complex.
AB  - Current viral delivery systems suffer from disadvantages that may limit the rate
      at which therapeutic gene expressing constructs can be tested both in vitro and
      in vivo. In this study, our focus was to develop a simple gene delivery system
      for the rapid and reproducible testing of therapeutic genes in cancer cells both
      in vitro and in vivo. We report here that a delivery system based on using a
      conjugated adenovirus in complex from with a DNA plasmid can be used for not only
      delivering genes in vitro but also for efficient and reproducible delivery in
      vivo. Replication defective adenoviral particles were chemically modified by
      covalent attachment of poly-L-lysine (PLL) to the viral capsid, allowing for
      direct interaction with DNA. The adenovirus/PLL conjugate (Adv/PLL) was used to
      deliver the plasmid pCMV/beta-gal to several different cancer cell lines (i.e.,
      lung, cervical) in vitro and resulted in transduction efficiencies as high as 52%
      as determined by histochemical staining. On direct intralesional injection of the
      Adv/PLL/DNA complex into subcutaneous tumors, transduction efficiencies greater
      than 35% could also be achieved. As a result, this system provides a simple
      method for delivering and testing therapeutic genes in cells both in vitro and in
      vivo, prior to the further development of gene therapy vectors for both malignant
      and benign disease.

PMID- 9171938
TI  - Delivery of the p53 tumor suppressor gene into lung cancer cells by an
      adenovirus/DNA complex.
AB  - An adenovirus/DNA complex was constructed by chemically linking poly-L-lysine to
      the capsid of the replication-defective adenovirus dl312, allowing for coupling
      with plasmid DNA by an ionic interaction. We have previously demonstrated that
      this adenovirus/DNA complex can efficiently transduce malignant cells with a
      plasmid expressing the beta-galactosidase gene both in vitro and in vivo. In this
      report, we show that this system can deliver a therapeutic gene that encodes for
      the tumor suppressor protein p53 to lung cancer cells, both in vitro and in vivo,
      leading to significant biological effects. Transfection of the p53-negative human
      lung cancer cell line H1299 with the adenovirus/DNA complex carrying a plasmid
      expressing the p53 gene resulted in high levels of p53 protein and induction of
      apoptosis. Injection of the complex carrying the p53 gene to subcutaneous tumor
      sites 5 days after tumor cell implantation resulted in a significant inhibition
      of tumorigenicity as measured by the number and size of tumors that developed 21
      days after treatment. Three and six injections of the complex carrying the p53
      gene into H1299 subcutaneous tumor nodules led to significant dose-related tumor
      growth suppression 18 days after the first injection compared with control
      treated tumors. This adenovirus/DNA complex, therefore, is capable of efficiently
      delivering the p53 gene into malignant cells in vitro and in vivo and now
      provides a general gene delivery vector that is simple to construct and capable
      of testing therapeutic genes in malignant cells.

PMID- 9171940
TI  - Responses of the dural circulation to electrical stimulation of the trigeminal
      ganglion in the cat.
AB  - 1. In cats anaesthetized with alpha-chloralose, electrical stimulation (ES) of
      the trigeminal ganglion produced a fall in blood pressure, a predominantly
      ipsilateral dilatation in the common carotid vascular bed and bilateral
      dilatation of the middle meningeal vascular bed. Section of the trigeminal root
      abolished these responses. 2. Dilatation in the middle meningeal artery was not
      affected by section of the cervical sympathetic trunk nor by the section of the
      seventh cranial nerve trunk. The dilator response was abolished by section of the
      spinal cord at the C3 level and by intravenous administration of bretylium (10
      mg/kg) or phentolamine (5 mg/kg). The response was significantly reduced by the
      prior administration of papaverine (10 mg/kg). 3. Functional adrenalectomy by
      means of a snare placed around the nerves and blood vessels supplying the adrenal
      glands significantly reduced the response. Electrical stimulation of the
      trigeminal ganglion was accompanied by a fall in circulating levels of
      noradrenaline and serotonin. 4. We conclude that ES of the trigeminal ganglion
      produces dilatation in the middle meningeal artery partly by autoregulation
      during the trigeminal depressor response and partly by a reduction in the
      circulating levels of noradrenaline. It differs from the dilatation seen in the
      general carotid circulation and the cortical microcirculation, which is mediated
      by parasympathetic nerves. There is no evidence that antidromic release of
      neuropeptides from sensory nerve endings in the dura plays a part in the
      dilatation.

PMID- 9171939
TI  - Antisense down-regulation of metallothionein induces growth arrest and apoptosis
      in human breast carcinoma cells.
AB  - The association of increased metallothionein (MT) gene expression in breast
      cancer with metastasis and poor prognosis has led us to investigate the
      hypothesis that inhibition of MT gene expression may elicit antiproliferative
      effects in breast carcinoma MCF7 cells. To monitor the effect of downregulation
      of MT protein on growth, MCF7 cells were transiently transfected by
      electroporation with an 18-mer MT antisense phosphorothioate oligomer (AO) or an
      18-mer random oligomer (RO). The MT-AO is complementary to the region 7 bases
      downstream from the AUG translational start site of the hMT-IIA gene.
      Transfection of MCE7 cells with the AO inhibited cell growth by 50-60% at 72
      hours when compared to control cells or the cells transfected with RO. The AO
      induced growth inhibition was associated with alterations in morphology
      suggestive of apoptotic cell death. This was further confirmed by DNA linker
      cleavage into oligonucleosomal fragments and decreased bcl-2 protein levels in AO
      transfected cells as opposed to the RO-transfected cells. Reverse transcriptase
      polymerase chain reaction analysis showed that AO induced a 2-fold increase in
      the levels of c-fos and p53 transcripts in comparison to RO which had no
      significant effect. Conversely, c-myc transcripts were decreased by 2.5-fold in
      the AO-transfected cells when compared to the controls. Furthermore, MCF7 cells
      transfected with an expression plasmid pBAcNEO-sMT-IIA encompassing human MT-IIA
      cDNA, constitutively driven by beta-actin promotor, caused a 2.5-fold increase in
      intracellular levels of MT, as judged by PCR and western blot analysis, in
      comparison to the cells transfected with pBAcNEO plasmid. In contrast to the AO
      induced growth inhibition, overexpression of cytoplasmic MT increased the cell
      multiplication by 2-fold compared with control cells or the cells transfected
      with the control plasmid 72 hours post-transfection. Moreover, the effects of AO
      on oncogene expression were reversed on increased expression of MT. These data
      suggest that overexpression of MT potentiates the growth of MCF7 cells, whereas
      downregulation of MT elicits antiproliferative effects.

PMID- 9171941
TI  - Endotoxin alters the systemic disposition of nitric oxide synthase inhibitors in
      the awake sheep.
AB  - 1. We evaluated the haemodynamic effects and systemic disposition of the nitric
      oxide synthase (NOS) inhibitor NL-nitro-L-arginine (NOLA) after intravenous
      (i.v.) administration of two different doses (5 and 20 mg/kg) in awake healthy
      sheep and awake sheep given a continuous i.v. infusion of endotoxin
      (lipopolysaccharide, 12 ng/kg per h, i.v., for 18 h). In addition, we determined
      the systemic disposition of another NOS inhibitor, NL-nitro-L-arginine
      methylester (L-NAME; 20 mg/kg, i.v.) in awake healthy sheep only. 2. NL-Nitro-L
      arginine produced a dose-dependent decrease in heart rate (HR) and cardiac output
      (CO) together with a dose-dependent increase in mean arterial pressure (MAP) and
      peripheral vascular resistance (PVR) when compared to baseline. In endotoxic
      sheep NOLA produced a greater increase in MAP and mean pulmonary arterial
      pressure (MPAP). 3. In healthy sheep there was a dose-related increase in total
      body clearance (Cl) of NOLA. The Cl increased from 0.028 L/min after the lower
      dose to 0.032 L/min after the higher dose. The infusion of endotoxin caused an
      increase in Cl of NOLA to 0.040 and 0.047 L/min, respectively, and a decrease in
      plasma slow half-life (t1/2) from 825 to 546 min and from 780 to 453 min,
      respectively. 4. NL-Nitro-L-arginine methylester was rapidly cleared from the
      plasma with a slow half-life of approximately 7.5 min and there was a
      simultaneous appearance of NOLA in the plasma. 5. These results support the view
      that nitric oxide has a significant role in regulating vascular tone in healthy
      and endotoxic sheep and indicate that the increases in Cl of NOLA with an
      increase in its dose and the presence of endotoxin will be important in
      influencing appropriate dosage regimens in clinical studies.

PMID- 9171942
TI  - Differences in the density of barosensitive neurons in the medulla of
      spontaneously hypertensive and Wistar-Kyoto rats.
AB  - 1. The density of barosensitive neurons in the medulla was examined in
      spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY)
      rats. In control experiments, rats were sham-operated, while in test experiments
      arterial baroreceptors were stimulated by pressor responses to i.v.
      administration of phenylephrine and the density of c-Fos-labelled neurons was
      immunocytologically examined. 2. In both control and test experiments, c-Fos
      labelled neurons were distributed in cardiovascular control sites: the nucleus
      tractus solitarii (NTS) and the caudal and rostral ventrolateral medullas
      (CVLM/RVLM). 3. In both WKY rats and in SHR, the total density of labelled
      neurons in test experiments was significantly higher than in control experiments.
      4. In control experiments, no significant difference was found in the
      distribution and density of labelled neurons in the NTS and in the CVLM/RVLM
      between rats and SHR. 5. In test experiments, no significant difference was found
      in the distribution and density of labelled neurons in the NTS between WKY rats
      and SHR. 6. In test experiments in SHR, the density of labelled neurons in the
      CVLM just caudal to the obex level was significantly higher than that in WKY
      rats, whereas the density of labelled neurons in WKY rats in the RVLM just
      rostral to the obex level was significantly higher than that in SHR. 7. These
      results indicate that stimulation of the arterial baroreceptor induces strain
      specific differences in the density of barosensitive neurons in the CVLM/RVLM
      near the obex level.

PMID- 9171943
TI  - Skeletal muscle resting metabolism in cold-acclimated rats: effect of age,
      noradrenaline and hyperosmolarity.
AB  - 1. A myothermic technique has been used to measure the resting metabolism of
      small bundles of a fast twitch muscle, extensor digitorum longus (EDL), and a
      slow twitch muscle, soleus (SOL), in 7-week-old rats. At 27 degrees C, mean (+/
      SEM) resting heat rates were 2.33 +/- 0.41 and 2.09 +/- 0.37 mW/g in EDL and SOL,
      respectively (n = 16). 2. Seven-week-old rats were cold acclimatized at 4 degrees
      C for 1-4 weeks and the metabolic rates of the fast and slow twitch muscles were
      monitored and compared with 7- and 11-week-old controls. There was a 160%
      increase in metabolic rate from week 7 to week 11, but the increase also occurred
      in the control group. 3. In accordance with several literature reports,
      noradrenaline at concentrations of 10(-7) and 10(-6) mol/L had no effect on
      either the control or cold-acclimatized resting heat rate. 4. The osmolarity of
      the physiological solution bathing the muscle bundles was increased by 100 mosmol
      using sodium sulphate. Basal metabolism increased by similar amounts
      (approximately 250%) in both the fast and slow muscle bundles. Periods of cold
      exposure had no significant effect on the magnitude of the increment. 5.
      Bumetanide, a potent inhibitor of Na(+)-Cl- co-transport, produced only a slight
      reduction in the heat increments caused by hyperosmolar challenge.

PMID- 9171944
TI  - Renin, prorenin, and renin gene expression in rats with acute nephrotic syndrome.
AB  - 1. The concentration of total, active and inactive renin was analysed in plasma,
      urine and kidney from control (C), pair-fed (PF) and nephrotic (NS) rats, as well
      as renin mRNA levels in kidney, liver and brain. 2. Nephrotic syndrome were
      induced by a single subcutaneous injection of puromycin aminonucleoside (PAN) and
      determinations were made 6 days after PAN injection. 3. Plasma total renin did
      not change, active renin increased in NS rats with respect to PF and C groups and
      in PF rats with respect to C. In contrast, the inactive renin percentage
      decreased in NS rats with respect to PF and C groups and in PF animals with
      respect to C. Total, active and inactive renal renin content did not change and
      active and inactive renin were significantly excreted by urine with no changes in
      the prorenin percentage with respect to C and PF groups. 4. In both NS and PF
      groups, renin mRNA levels did not change in any of the tissues studied. In
      another group of rats, kidney renin mRNA levels were measured on days 1, 3, 5 and
      7 after PAN injection and no time-course changes in its expression were found. 5.
      These results suggest that renin gene expression is not altered in acute
      nephrotic syndrome and that plasma renin concentration is regulated at the
      translational or post-translational level in this experimental model.

PMID- 9171945
TI  - Alterations of mRNA levels of alpha 1-adrenoceptor subtypes with maturation and
      ageing in different rat blood vessels.
AB  - 1. Alterations of mRNA levels of alpha 1-adrenoceptor subtypes during maturation
      and ageing were determined by reverse transcription-polymerase chain reaction (RT
      PCR) in aortae and renal, pulmonary and mesenteric arteries isolated from 3, 12
      and 24-month-old rats. 2. The steady state levels for alpha 1A-, alpha 1B- and
      alpha 1D-adrenoceptors in aorta declined with maturation and ageing. In renal
      artery there was a decrease in mRNA for the alpha 1B-adrenoceptor in aged rats.
      However, in mesenteric and pulmonary arteries there were no changes in mRNA
      levels for the three subtypes of alpha 1-adrenoceptors as a result of maturation
      and ageing. 3. The results suggest that expression of alpha 1-adrenoceptors is
      changed heterogeneously in different blood vessels during maturation and ageing
      in rats.

PMID- 9171946
TI  - Effects of diet on measurement of nitric oxide metabolites.
AB  - 1. The present study investigated whether a low nitrate/nitrite diet could
      minimize variability in the measurement of endogenous plasma and urine nitric
      oxide (NO) metabolites, nitrate and nitrite (NOx) in normal subjects. 2. Nitrate
      and nitrite concentrations were measured in plasma and urine as indicators of NO
      production in six subjects during a free diet and then during a low
      nitrate/nitrite diet for 6 days. 3. The plasma concentration and 24 h urine
      NOx/creatinine ratio were significantly lower on the low nitrate/nitrite diet
      than on the free diet (P < 0.01). Nitric oxide production appeared to vary
      greatly within and between subjects, but these variations were substantially
      decreased by the fourth day of a low nitrate/nitrite diet. 4. Human plasma and
      urine NOx measurements should be determined after a low nitrate/nitrite diet for
      at least 4 days.

PMID- 9171947
TI  - Diurnal effects of fluoxetine and naloxone on the human hypothalamic-pituitary
      adrenal axis.
AB  - 1. Central serotonergic pathways are hypothesized to be involved in the
      stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue
      release by both circadian- and stress-induced mechanisms. We aimed to investigate
      this hypothesis by measuring the effect of the highly specific serotonin re
      uptake inhibitor fluoxetine (FX) on ACTH and cortisol release in the morning and
      in the afternoon in humans, both by itself and in combination with the opioid
      antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an
      endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory
      to hypothalamic corticotropin-releasing hormone (CRH) secretion. Serotonergic
      agents may act directly or indirectly through these central noradrenergic
      pathways and, if so, would be expected to be additive to or synergistic with Nal
      in causing ACTH and cortisol release. 2. Oral FX (40 mg) was given at
      approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later,
      to normal human volunteers. Plasma ACTH and cortisol levels were measured for 5 h
      after FX dosing. 3. Fluoxetine produced a small but non-significant increase in
      Nal-stimulated ACTH and cortisol release in both morning and afternoon studies.
      Naloxone alone did not cause different ACTH and cortisol responses in the morning
      and afternoon. 4. These results suggest that serotonergic pathways are not major
      regulators of the hypothalamic-pituitary-adrenal axis in humans or that FX has
      counteracting acute inhibitory effects on the axis, such as inhibition of
      hypothalamic arginine vasopressin secretion, which has been demonstrated in
      chronic animal studies.

PMID- 9171948
TI  - Genetic factors associated with altered sodium transport in human hypertension: a
      twin study.
AB  - 1. Na+/H+ antiporter/exchange activity (NHE) in human cheek epithelial cells was
      assessed in 288 female twins and siblings. The genetic contribution of factors to
      NHE activity was assessed in 128 matched twin pairs (76 monozygotic (MZ); 52
      dizygotic (DZ)). 2. There was a small reduction in NHE with age and body mass
      index. The significant correlations (+/-their standard error (SE)) within MZ and
      DZ pairs of twins were 0.54 +/- 0.08 and 0.26 +/- 0.13, respectively, implying
      that genetic factors accounted for 54% of the variance in age-adjusted NHE. There
      was no cross-sectional relationship between NHE and measures of blood pressure.
      Based on within-pair differences, however, there was a weak negative association
      (r = 0.22; P < 0.05) between mean arterial pressure and NHE. 3. It remains to be
      determined whether NHE in cheek cells is associated with blood pressure tracking
      over time in young females.

PMID- 9171949
TI  - PCR-SSCP analysis of the glucocorticoid-responsive element of the atrial
      natriuretic peptide gene in familial primary open-angle glaucoma.
AB  - 1. Familial primary open-angle glaucoma (POAG) is a heterogeneous disease of
      unknown aetiology and the elucidation of the underlying genetic mechanisms
      contributing to phenotypic expression will be essential if earlier diagnosis of
      at-risk individuals and more specific medical treatment can be achieved. In a
      significant percentage of patients with POAG, intraocular pressure increases in
      response to topical ocular glucocorticoids. 2. Atrial natriuretic peptide (ANP)
      assists in the regulation of intraocular pressure levels and binding of the
      glucocorticoid receptor dimer to the glucocorticoid-responsive element in intron
      2 of the ANP gene has been shown to increase ANP mRNA levels in vitro. We
      amplified and examined this sequence in the ANP gene by PCR-SSCP analysis in 100
      patients with familial POAG and in 60 normal control subjects. No base
      alterations in the amplified product were found. 3. Thus, the present study found
      no evidence for an alteration in the sequence of the glucocorticoid-responsive
      element of the ANP gene that could alter ANP gene transcription in patients with
      familial POAG. The mechanism responsible for the increase in intraocular pressure
      levels in response to glucocorticoids is most likely independent of the
      glucocorticoid-responsive element in the ANP gene.

PMID- 9171950
TI  - Effects of 17 beta-oestradiol on vascular responses in the in situ blood-perfused
      mesentery of Wistar-Kyoto rats.
AB  - 1. To determine whether endogenous oestrogen plays a role in pregnancy induced
      decreased vascular reactivity we have examined the effects of 17 beta-oestradiol
      on vasoconstrictor responses to various stimuli using an in situ blood-perfused
      mesenteric vascular preparation in Wistar-Kyoto (WKY) rats. 2. Daily
      administration of 17 beta-oestradiol (500 micrograms/kg, s.c.) for 15 days
      significantly enhanced mesenteric vasoconstrictor responses to noradrenaline
      (NA), without affecting responses to the electrical stimulation of sympathetic
      nerves (ES) and angiotensin II (AngII). 3. Nitric oxide (NO) synthesis inhibition
      by nitro-L-arginine methyl ester (L-NAME; 100 mg/kg, i.v.) significantly
      potentiated mesenteric vasoconstrictor responses to all stimuli in both 17 beta
      oestradiol-treated and control animals. The difference in NA responses between
      groups was diminished following NO synthesis inhibition. 4. These findings do not
      support the hypothesis that increased endogenous oestrogen plays a role in
      decreased mesenteric vascular reactivity in pregnancy. However, responses to
      oestrogen may be dose-dependent and enhancement of vasoconstrictor responses to
      NA may be relevant to oral contraceptive-induced hypertension.

PMID- 9171951
TI  - Nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester
      affects blood pressure and cardiovascular structure in the genetically
      hypertensive rat strain.
AB  - 1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide synthase (NOS)
      inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used as a tool to
      investigate further a possible endothelial defect in the New Zealand genetically
      hypertensive (GH) rat strain compared with its normotensive (N) control strain.
      2. N omega-nitro-L-arginine methyl ester was given to GH and N groups in their
      drinking water from age 7-10 weeks (10 mg/kg per day for week 1 and 2 and then 5
      mg/kg per day for week 3). Tailcuff blood pressure (BP) was measured weekly and
      at the end of the experiment the mesentery was fixed by perfusion, second order
      branches of the mesenteric artery were embedded in Technovit and stained sections
      were used to quantify the structure of the mesenteric resistance arteries (MRA).
      The heart was removed and weighed for determination of left ventricular (LV)
      mass. 3. In GH rats, BP and LV mass were significantly raised by L-NAME, while in
      N rats L-NAME treatment significantly elevated BP, but had no effect on LV mass.
      4. In GH rats, the media width was significantly increased by L-NAME treatment (P
      < 0.01); lumen diameter remained unchanged. Thus, the ratio of media width/lumen
      diameter (M/L) was significantly increased by exacerbation of the hypertrophic
      outward remodelling characteristic of the GH strain. There were no significant
      changes in the M/L ratio in L-NAME-treated N rats. 5. Thus, in the GH strain,
      cardiovascular structure is more sensitive to NOS inhibition than either its N
      control strain or (on evidence from the literature) the spontaneously
      hypertensive rat strain.

PMID- 9171952
TI  - A nitric oxide donor (spermine-NONOate) prevents the formation of neointima in
      rabbit carotid artery.
AB  - 1. In the present study we investigated the effect of spermine diazeniumdiolate
      (spermine-NONOate), a nitric oxide donor, on the early development of atheroma
      like lesions induced by a peri-arterial collar in rabbits. 2. Spermine-NONOate
      was given locally by incorporating the compound (1 mg/mL) into a silastic collar,
      which was applied on one common carotid artery of rabbit while the other carotid
      artery had a placebo collar (without compound) applied. 3. Fourteen days
      postimplantation, both carotid arteries were dissected free for histological
      study (n = 6). 4. After 14 days with collars, treatment with spermine-NONOate had
      significantly reduced (by 74%) the thickness of the neointima in comparison with
      the contralateral collared artery without compound. Blood pressure did not change
      during treatment. Nitric oxide, detected as nitrite, was still released from
      spermine-NONOate silastic collars after 14 days implantation. 5. These results
      suggest that locally administered spermine-NONOate is effective in slowing the
      development of neointima in this model.

PMID- 9171953
TI  - Chronic intrarenal infusion of low-dose angiotensin II in dogs increases arterial
      pressure without impairment of renal function.
AB  - 1. To determine whether chronic angiotensin II (AngII) infusion into the renal
      artery, at a dose which increases systemic arterial pressure, reduces glomerular
      filtration rate (GFR) and renal blood flow, AngII was infused at 0.5 ng/kg per
      min into the renal artery or intravenously in chronically instrumented dogs for 1
      month. 2. Mean arterial pressure (MAP) rose significantly (P < 0.05) during the
      infusion of AngII into the renal artery (+7 +/- 2 mmHg on days 26-30). There were
      no significant changes in GFR or renal blood flow. When the same dose of AngII
      was infused intravenously, MAP did not change significantly (-2 +/- 2 mmHg) and
      there were no significant changes in GFR or in renal blood flow. 3. We conclude
      that AngII infused into the renal artery for 1 month, at a dose which was
      initially subpressor, causes a rise in arterial pressure that is not associated
      with impairment of renal function.

PMID- 9171954
TI  - Association of the brain natriuretic peptide gene with blood pressure and heart
      weight in the rat.
AB  - 1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are
      important in the control of body fluid homeostasis, blood pressure (BP)
      regulation and vascular remodelling. The genes for these peptides may, therefore,
      be involved in the pathogenesis of genetic hypertension. We have previously
      described a quantitative trait locus (QTL) for BP in the ANP gene region on rat
      chromosome 5. We have now assessed the possibility that this QTL lies at the
      closely linked BNP locus. 2. Intra-arterial BP and heart weight were measured in
      12-week-old (n = 207) and 24-week-old (n = 88) F2 rats derived from crosses
      between Wistar-Kyoto normotensive rats and spontaneously hypertensive rats. We
      designed polymerase chain reaction primers to amplify a microsatellite in the BNP
      gene from genomic DNA. Analysis of variance was used for cosegregation analysis.
      Linkage mapping and localization of QTL was performed using the Mapmaker computer
      package. 3. A significant correlation was found between genotype for the BNP gene
      and systolic BP (P < 0.001) in 12-week-old rats. The ANP gene, but not the BNP
      gene, was associated with systolic BP in 24 week rats. There was no segregation
      of heart weight with BNP genotype at 12 or 24 weeks of age. The BNP gene mapped
      approximately 20 cM from the ANP gene in our rat hybrids, away from the
      previously described QTL. There was evidence for a second BP locus near to but
      distinct from the BNP gene. 4. These results suggest that BP QTL are present in
      the natriuretic peptide gene region but that the ANP and BNP genes themselves
      have no major effect on BP in this cross.

PMID- 9171955
TI  - Cardiac hypertrophy in diabetic spontaneously hypertensive rats: role of
      angiotensin II?
AB  - 1. In the present study the role of angiotensin II (AngII) in the development of
      cardiac hypertrophy in diabetes combined with hypertension was investigated. 2.
      Diabetes was induced in 8-week-old male spontaneously hypertensive rats (SHR) by
      intravenous injection of streptozotocin (45 mg/kg bodyweight). Diabetic SHR were
      treated with the angiotensin-converting enzyme (ACE) inhibitor ramipril at a dose
      of 0.4 mg/kg per day. 3. Twelve weeks following the onset of diabetes, hearts
      were arrested in diastole and were perfusion-fixed. The right ventricle and left
      ventricle plus septum were weighted and the volume of the ventricular walls was
      determined using the Cavalieri principle. 4. Induction of diabetes in SHR led to
      a significant reduction in bodyweight compared with non-diabetic control SHR and
      this was not affected by ramipril treatment. The development of hypertension was
      not as great in diabetic SHR compared with controls, such that at 12 weeks
      following the onset of diabetes systolic blood pressure (SBP) averaged 191 +/- 3
      and 230 +/- 4 mmHg in diabetic SHR and controls, respectively. Ramipril treatment
      significantly lowered SBP in diabetic SHR. 5. The left ventricle plus septum
      volume:bodyweight ratio (LV vol:BW) was significantly higher in diabetic SHR
      compared with controls (3.83 +/- 0.19 and 3.26 +/- 0.16 mm3/g, respectively).
      Ramipril treatment did not affect growth of the left ventricle in diabetic SHR
      with the LV vol:BW ratio averaging 3.95 +/- 0.14 mm3/g. Similar trends on growth
      were observed in the right ventricle. 6. In conclusion, the development of
      cardiac hypertrophy in diabetic SHR appears to occur by mechanisms independent of
      AngII and the elevation of blood pressure.

PMID- 9171956
TI  - Stimulation of the gastric sodium monitor reduces hepatic angiotensin-converting
      enzyme activity.
AB  - 1. The natriuresis engendered by stimulation of the gastric sodium monitor is
      mediated in part by a decrease in the circulating concentration of angiotensin II
      (AngII). This decrease is due to decrease in synthesis rather than to an increase
      in metabolism. We investigated the role of changes in plasma and hepatic
      angiotensin-converting enzyme (ACE) activity in this decrease in AngII synthesis.
      2. Male Sprague-Dawley rats were equilibrated on a low-sodium diet for 7 days. On
      the day of experiment, rats were anaesthetized and received either a sodium load
      of 1.5 mmol/kg as 3 mol/L saline or an equivalent volume of an iso-osmotic urea
      solution by direct gastric puncture. Blood was sampled and livers were harvested
      at 0 and 30 min after sodium or urea administration. Angiotensin-converting
      enzyme was measured in serum and tissue homogenates by generation of histidyl
      leucine. 3. In the liver, ACE activity decreased from control after both sodium
      (P < 0.005) and urea (P < 0.025) administration. The decrease was greater in the
      group that received saline compared with rats that received urea (P < 0.05).
      Serum ACE decreased in response to urea (P < 0.025) but not sodium
      administration. 4. We conclude that stimulation of the gastric sodium monitor
      results in a decrease in ACE activity in the liver. This decrease in ACE activity
      may be contributory to the decrease in AngII synthesis.

PMID- 9171957
TI  - Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of
      diabetic nephropathy.
AB  - 1. To investigate the role of nitric oxide (NO) in diabetic nephropathy the
      effect of nitric oxide synthase (NOS) inhibition by NG-nitro-L-arginine methyl
      ester (L-NAME) was observed in a streptozotocin diabetic spontaneously
      hypertensive rat (SHR) model. 2. Two groups of SHR (n = 8) with streptozotocin
      induced diabetes were studied. One group was given L-NAME 5 mg/kg bodyweight per
      day in the drinking water for 8 weeks while both groups received daily
      subcutaneous injections of Ultratard insulin. Creatinine clearance, urinary
      protein excretion, urinary nitrate concentration and systolic blood pressure were
      measured at fortnightly intervals. Rats were killed at 8 weeks and plasma
      angiotensin II (AngII) was measured by radioimmunoassay. 3. Renal function
      (endogenous creatinine clearance) remained stable in both groups. In the L-NAME
      group, however, there was a progressive increase in proteinuria that was highly
      significant at 6 weeks (22.1 +/- 2.9 compared with 6.5 +/- 0.7 mg/ 24 h per 100 g
      in control SHR diabetic rats P < 0.001). 4. Systolic blood pressure was
      significantly elevated in the L-NAME group throughout the study compared with the
      control group. 5. Plasma AngII was significantly elevated in the L-NAME group
      compared with controls (42.8 +/- 10.3 vs 15.1 +/- 1.9 pmol/L, respectively; P <
      0.05). 6. Activation of the renin-angiotensin system may account, at least in
      part, for the resulting vasoconstrictor activity with chronic nitric oxide
      depletion.

PMID- 9171958
TI  - Association analysis of six candidate genes in a sample of Australian
      hypertensive patients.
AB  - 1. Essential hypertension is characterized by increased vascular resistance due
      to narrowing of the small arterioles. This may be influenced by vasoactive
      substances, cell growth and vascular remodelling. 2. A sample of Australian
      hypertensive and normotensive subjects was investigated for association with
      genetic markers which are candidates for a role in blood pressure (BP) regulation
      due to potential effects on vascular diameter. 3. The six markers used were for
      genes encoding vasoconstrictors, growth factors and a structural protein of the
      extracellular matrix. 4. No significant association of any of the markers used
      was found with BP status in this sample of patients.

PMID- 9171959
TI  - Effects of oestrogen and progesterone on age-related changes in arteries of
      postmenopausal women.
AB  - 1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin
      may have different effects on arterial structure and function. To examine this
      question, carotid artery intima-medial thickness (IMT) and indices of systemic
      and carotid arterial compliance were measured in groups of older men,
      postmenopausal women not on HRT (non-HRT) and those women on long-term HRT with
      oestrogen alone (HRT-E) or oestrogen plus progestin (HRT-EP). 2. Sixty men, 90
      postmenopausal women taking HRT and 91 not taking HRT participated in the study.
      The groups were similar for age, body mass index, numbers of smokers, physical
      activity, alcohol intake and blood pressure. 3. Plasma total cholesterol was
      reduced and high-density lipoprotein-cholesterol was increased in the HRT group
      compared with the non-HRT group; low-density lipoprotein-cholesterol,
      triglyceride and lipoprotein (a) values were similar in these two groups. Results
      for HRT-E and HRT-EP subgroups were similar. 4. Carotid IMT was significantly
      reduced in the HRT group compared with men and non-HRT groups. Results for HRT-E
      and HRT-EP subgroups were similar. 5. Mean systemic arterial compliance (SAC) was
      significantly greater in men than in women and was related to age; SAC was higher
      in both HRT-E and HRT-EP groups compared with the non-HRT group. Indices of
      carotid stiffness were similar in men and in non-HRT groups. The HRT-EP group
      showed increased carotid stiffness compared with the HRT-E group. 6. There is an
      apparent protective effect of long-term oestrogen therapy on carotid IMT and age
      related changes in arterial stiffness. Progestin does not alter the IMT effects
      but may adversely influence arterial stiffness.

PMID- 9171960
TI  - Acute but not chronic angiotensin-converting enzyme inhibition induces enzyme
      synthesis in the glomerulus of the spontaneously hypertensive rat.
AB  - 1. Treatment with angiotensin-converting enzyme (ACE) inhibitors slows the rate
      of progression of nephropathy in the spontaneously hypertensive rat (SHR) with
      streptozotocin-induced diabetes. Paradoxically, however, chronic ACE inhibitor
      therapy has been reported to be associated with induction of ACE in the plasma.
      We sought to determine whether induction also occurred in the glomerulus. 2.
      Seven days after induction of diabetes rats were randomized to receive
      perindopril (4 mg/kg per day) in the drinking water or water alone. Blood
      glucoses were maintained 6-10 mmol/L by daily ultralente insulin. Rats were
      killed after 1 and 12 weeks of ACE inhibitor therapy and the kidneys were
      harvested. Angiotensin-converting enzyme activity was determined in isolated
      glomeruli before and after removal of perindopril and reconstitution with zinc
      sulphate. 3. After 1 week of ACE inhibitor therapy, glomerular ACE was
      significantly greater after removal of perindopril than either before its removal
      (P < 0.025) or in the untreated controls (P < 0.025). After 12 weeks of therapy,
      ACE activity was significantly lower in the perindopril-treated group than in the
      untreated controls (P < 0.025). There was no increase in ACE activity following
      removal of perindopril. 4. These studies suggest that short-term ACE inhibition
      is associated with induction of ACE in the glomerulus. However, there was no
      increase in ACE activity after removal of perindopril, suggesting that induction
      of synthesis of this enzyme in the glomerulus does not occur during chronic ACE
      inhibition.

PMID- 9171961
TI  - Stimulation of gastric osmoreceptors but not the sodium monitor increases renal
      angiotensin-converting enzyme activity.
AB  - 1. Stimulation of the gastric sodium monitor has been reported to cause a
      decrease in renal nerve activity and also a decrease in plasma renin activity in
      renal venous blood. This suggests that changes in sympathetic nerve activity and
      in the intrarenal renin-angiotensin system may mediate the natriuresis that
      occurs following gastric sodium administration. In the present study we sought to
      determine whether gastric sodium administration also modulates angiotensin
      converting enzyme (ACE) activity in the kidney. 2. Male Sprague-Dawley rats were
      equilibrated on a low-sodium (0.008%) diet for 7 days. On the day of the
      experiment, rats were anaesthetized and kidneys were harvested and immediately
      snap frozen at 0 and 60 min after intragastric administration of a saline load
      (1.5 mmol/kg as 3 mol/L saline) or an equivalent volume of iso-osmotic urea
      (5.95%). Angiotensin-converting enzyme activity was determined by incubation of
      kidney homogenates with hippuryl-histidyl-leucine and fluorometric assay of the
      histidyl-leucine generated. 3. Angiotensin-converting enzyme activity in the
      kidney increased in response to the intragastric administration of both sodium
      chloride and urea. Angiotensin-converting enzyme activity increased significantly
      from control levels (189.9 +/- 24.3 nmol/min per g protein) by 60 min in both
      NaCl-and urea-treated groups (492.3 +/- 27.3 and 468.6 +/- 28.7 nmol/min per g
      protein, respectively; P < 0.0005). 4. We conclude that instillation of sodium
      chloride or isoosmotic urea into the stomach increase ACE activity in the kidney.
      The results of the present study suggest that this effect is due to changes in
      osmolality rather than stimulation of the gastric sodium monitor.

PMID- 9171962
TI  - Post-exercise cutaneous hyperaemia resulting from local exercise of an extremity.
AB  - Large changes in skin blood flow occur after exercise. Most studies have
      concentrated on the systemic effects of vigorous exercise on skin blood flow. We
      were interested in the post-exercise response in the neighbourhood of focal
      exercise. We used a painless neuromuscular electronic stimulator to exercise the
      muscles of the forearm, producing flexion of the fingers. There was no change in
      blood pressure and only a small increase in heart rate during this exercise. We
      measured blood flow during a 5-min pre-exercise period and a 5-min post-exercise
      period at the forearm, at the dorsum of the index finger and on the pad of the
      index finger. We also measured values on the contralateral non-exercised
      extremity during exercise as well as during matched time periods in control
      experiments with no exercise. Exercise did elicit an increased blood flow in the
      post-exercise period at all three sites compared with the control experiments
      with no exercise and on the contralateral extremity. For example, the increase in
      blood flow at the finger dorsum was 2.1 +/- 0.1 ml (min 100 g)-1 after exercise
      compared with -0.08 +/- 0.09 ml min-1 100 g-1 during the control experiment and
      0.1 +/- 0.1 ml (min 100 g)-1 on the contralateral arm (all P < 0.01). The local
      application of heat at the site of blood flow monitoring produced a substantial
      increase in the post-exercise response at the two finger locations [27.4 +/- 0.4
      ml (min 100 g)-1 at the finger dorsum], but not at the arm. This is the first
      demonstration that highly focal exercise, unaccompanied by a systemic
      haemodynamic response, can elicit a post-exercise cutaneous hyperaemia. Local
      heating produced a large synergistic increase in the post-exercise hyperaemia at
      sites with arteriovenous microvascular perfusion but not at sites with primarily
      nutritive perfusion. These findings show that local vasoregulatory changes occur
      in response to exercise, even in the absence of whole-body haemodynamic and
      thermal change.

PMID- 9171963
TI  - Components of carbon monoxide transfer at different alveolar volumes during
      mechanical ventilation in pigs.
AB  - We studied the effect of increasing alveolar volume on pulmonary carbon monoxide
      transfer (DLCO) and its components, i.e. membrane diffusing capacity (DM) and
      capillary blood volume (Qc), during mechanical ventilation in eight anaesthetized
      and paralysed healthy pigs (mean weight 11.2 kg). We used an inspiratory pause
      procedure for simulation of the single-breath technique, and inflated 15, 20, 25
      and 30 ml kg-1 in random order. DM and Qc were derived using the Roughton-Forster
      equation. Per litre BTPS increase in effective VA, DLCO (inspiratory oxygen
      fraction 0.30) decreased on average by 11.8 mumol s-1 kPa-1, DM slightly
      increased by 2.7 mumol s-1 kPa-1 and Qc decreased by 241 ml. The increase in DM
      was much smaller than might be expected from the increase in VA, which we ascribe
      to a loss of the alveolar capillary membrane for gas transfer because of the
      concomitant decrease in Qc. The decrease in Qc may be explained by a squeezing
      effect of the intrapulmonary pressure rise on the alveolar wall and by stretching
      of lung tissue.

PMID- 9171964
TI  - Indirect calorimetry during treadmill walking--a study of two methods.
AB  - Walking is a complex process and the physiotherapist must focus on physical signs
      as well as functional and practical tests to evaluate treatment. Measurement of
      energy expenditure during level walking is a useful objective parameter for
      assessing walking as being a valuable supplement to evaluate the outcome of
      physiotherapy. This study had two purposes. The first purpose was to investigate
      whether sampling and measurement of oxygen consumption were reproducible when
      using two different devices during walking on a treadmill. A second purpose was
      to find out whether the measurements were sensitive enough to reveal differences
      in energy expenditure and respiratory quotient (RO) during different walking
      speeds. Ten healthy students (mean age 22 years; range 20-25 years) volunteered
      in the test-retest of a slightly adjusted Deltatrac metabolic monitor. Thirteen
      volunteers (mean age 45 years; range 31-57 years) participated in the test-retest
      of Sensormedics 2900. In the first test, the subjects walked for 10 min in order
      to get a steady state both at an individual comfortable speed and at a preset
      speed. The retest was done with the same design and within 2 weeks. Nobody
      experienced any discomfort during the tests. The repeatability of measuring
      energy expenditure and RQ was acceptable for both methods and the methods were
      sensitive in revealing differences in energy expenditure during different walking
      speeds. The RQ were, however, too low when using the Deltatrac monitor, probably
      as a result of low air flow. We therefore conclude that only the method using
      Sensormedics 2900 may be used for the evaluation of energy expenditure during
      walking on a treadmill.

PMID- 9171965
TI  - Intraocular pressure: a comparative analysis in two sexes.
AB  - Some investigators have reported higher intraocular pressure (IOP) levels in
      women and others in men, while some have failed to find any sex difference. It
      has been reported that IOP increases with age in Western populations, whereas it
      decreases in Japanese. Because of these contrasts, this study was planed to
      determine the influence of sex on IOP in various age groups in an apparently
      healthy population from Rawalpindi, Pakistan. Depending upon age, 5307 men and
      2388 women were divided into seven groups. All subjects were examined according
      to standard protocols. IOP was measured by Goldmann applanation tonometer. IOP
      progressively increased until the age interval of 61-70 years in both sexes. The
      increase became statistically significant in the age interval of 51-60 years in
      men, while in women it was one decade earlier. The difference between the two
      sexes increased significantly after the age of 40 years. Ocular hypertension (IOP
      > 21 mmHg) was found in 5.3% and 2.1% of women and men respectively. In both
      sexes, distribution of IOP did not fit a normal bell-shaped curve but skewed to
      the right. In Pakistan, IOP increases with age in both sexes, but more markedly
      in women. Left eye IOP was negligibly higher in all age groups of both sexes.
      Ocular hypertension was found more in female than in male subjects. Menopause is
      associated with an increase in IOP. Menstrual cycle had no influence on IOP.
      Knowledge of the normal level of IOP in various age groups of both sexes may help
      glaucoma screeners.

PMID- 9171966
TI  - Prediction of post-operative cardiopulmonary function using perfusion
      scintigraphy in patients with bronchogenic carcinoma.
AB  - Both ventilation and perfusion scintigraphy are accurate predictors of post
      operative ventilatory function. Previous attempts to predict post-operative
      exercise capacity after lung resection using radioisotope scintigraphy are few
      and results are conflicting. We studied 32 patients before and 6 months after
      pulmonary resection for bronchogenic carcinoma to assess the value of lung
      perfusion scintigraphy for the prediction of post-operative forced lung volumes
      and parameters on maximum exercise, including maximum ventilation and maximum
      oxygen uptake. Nine patients were lost to follow-up, and these patients differed
      from the reinvestigated patients only in the staging of the pulmonary carcinoma
      and not in preoperative lung function or exercise capacity. We found a clear
      relationship between the values predicted from a preoperative perfusion
      scintigraphy, spirometry and a maximum exercise study and the observed values
      measured 6 months post-operatively. The method underestimated the post-operative
      values of both spirometric and exercise measurements, especially in the higher
      range. Only in a few cases were the post-operative observed values less than the
      predicted values, and in these cases the difference was without clinical
      significance. Unexpected post-operative respiratory insufficiency was not
      observed. In conclusion, in patients in whom a pulmonary resection was performed,
      not only the post-operative spirometric values, but also the more functional
      related maximum exercise data can be predicted through the knowledge of a
      preoperative perfusion scintigraphy.

PMID- 9171967
TI  - Plasma nitric oxide metabolite in women with primary Raynaud's phenomenon and in
      healthy subjects.
AB  - Primary Raynaud's phenomenon (PRP) is characterized by cold- or stress-induced
      transient attacks of impaired skin circulation in fingers and/or toes. PRP
      displays seasonal variation with less severe symptoms in the summer. The
      aetiology has not been clarified. The aims of the present study were (a) to
      assess the influence of cold exposure on the plasma levels of the nitric oxide
      (NO) metabolite, nitrate, in patients with PRP and in healthy control subjects;
      and (b) to investigate whether there is a seasonal variation in these plasma
      levels. In a group of women with PRP and matched control subjects, venous blood
      was sampled before and at the end of a 40-min period of whole-body cooling. The
      study was performed with the same protocol on two occasions; once in the winter
      and once in the summer. A seasonal variation was detected with higher plasma
      levels of nitrate in the winter than in the summer, both in PRP and in control
      subjects. However, the plasma level of nitrate was not changed in response to
      cold exposure on any occasion, either in the patient or in the control group. Our
      study indicates that NO formation is up-regulated in response to cold weather in
      both study groups. However, NO formation does not seem to be increased in
      response to whole-body cooling, either in PRP patients or in healthy subjects.
      Further investigations are required to reveal whether the observed seasonal
      variation in NO formation is a universal phenomenon in man.

PMID- 9171969
TI  - Effect of exercise training and detraining on gas exchange kinetics in patients
      with chronic obstructive pulmonary disease.
AB  - Symptom-limited incremental exercise tests are used to estimate the training
      effect on patients with chronic obstructive pulmonary disease (COPD). However,
      there is a need for objective parameters for measurement on submaximal exercise
      testing. The purpose of this study was to assess the usefulness of measurement of
      oxygen uptake (VO2) kinetics during a constant work rate exercise test of
      patients with COPD after exercise training. Eleven patients with COPD performed
      exercise tests before and after cycle ergometer training on 3 days per week for 8
      weeks; they then went without training for 5 months and performed the same tests.
      They performed an incremental exercise test to symptom-limited maximum and a
      constant work rate exercise test for 6 min on a cycle ergometer. The time
      constant of VO2 during the onset of constant work rate exercise was significantly
      decreased (from 63.5 +/- 7.8 s to 53.2 +/- 8.0 s) after exercise training (P =
      0.021), but was significantly increased (to 73.4 +/- 14.9 s) after 5 months
      without training (P = 0.001). The oxygen pulse at steady state during constant
      work rate exercise testing was significantly increased after exercise training
      but decreased 5 months later. The change in blood lactate from rest to steady
      state during constant work rate exercise was significantly decreased after
      exercise training, but increased 5 months later. Measurement of the time constant
      of VO2 and oxygen pulse during constant work rate exercise are useful for the
      objective evaluation of the training effect of patients with COPD.

PMID- 9171968
TI  - Normal levels of energy expenditure in patients with reported "low metabolism'.
AB  - The present study examined the hypothesis that patients with apparent diet
      resistant obesity have subnormal energy expenditure. Ten biochemically euthyroid
      patients (eight women and two men), aged 21-76 years, with either excessive
      gynoid fat distribution or obesity (BMI 23.8-41.0), were referred to the
      department thought to be suffering from a low metabolic rate syndrome since
      dietary records showed very low energy intake (< 5 MJ day-1) in combination with
      failure to lose weight on low-energy diets. Twenty-four-hour energy expenditure
      (24-h EE), basal energy expenditure (BEE) and sleeping energy expenditure (SEE)
      were measured in a respiration chamber on a fixed activity programme. The
      patients consumed a diet containing 37 energy-per cent (E%) fat, 47 E%
      carbohydrate and 16 E% protein. The individual energy intake was estimated from a
      previously established algorithm between 24-h EE and fat-free mass (FFM)
      estimated by bioimpedance. Results were compared with equivalent values in a
      reference population of 76 subjects ranging from normal weight to obese. No
      evidence of low metabolism was found in terms of adjusted 24-h EE in the patients
      with diet resistance when compared with the control group (9263 +/- 819 kJ vs.
      9211 +/- 558 kJ). No differences were found when comparing adjusted BEE and SEE
      in the two groups (7655 +/- 727 vs. 7411 +/- 770 kJ 24 h-1 and 7048 +/- 672 vs.
      6911 +/- 408 kJ 24 h-1). The physical activity index (PAI) during the chamber
      stay was likewise within normal values (1.32 +/- 0.07 vs. 1.34 +/- 0.04; NS).

PMID- 9171970
TI  - Post-exercise depression of baroreflex slowing of the heart in humans.
AB  - In normal human subjects, we tested whether a 20- to 30-min period of rhythmic
      exercise, intended to provoke strong activation of the sympathetic nerves, would
      lead to prolonged inhibition of vagally mediated bradycardia evoked reflexly by
      stimulation of the baroreceptors by neck suction. Negative pressure within the
      neck cuff (-40 to -80 mmHg) reflexly evoked a reproducible increase in pulse
      interval. Following exercise, this increase in pulse interval was reduced from
      444 +/- 104 ms to 76 +/- 57 ms (mean +/- SEM). Recovery time was 42 +/- 9 min.
      These findings demonstrate a prolonged attenuation of cardiac vagal action
      following rhythmic exercise in normal human subjects. It is known that
      neuropeptide Y (NPY) is released from cardiovascular sympathetic nerves, that it
      attenuates cardiac vagal action and that plasma levels of NPY are elevated for a
      prolonged period after exercise. Therefore, it is proposed that NPY, released
      from sympathetic nerves during exercise, attenuates reflexly evoked cardiac vagal
      action for a prolonged period after exercise ends.

PMID- 9171971
TI  - Dynamic muscle strength alterations to detraining and retraining in elderly men.
AB  - To investigate the effects of cessation and subsequent resumption of training on
      muscle strength in elderly men, 11 men (aged 65-77 years), just completing a 24
      week randomized controlled trial of recombinant human growth hormone (rhGH) and
      resistance exercise (rhGH, n = 6; placebo, n = 5), detrained for 12 weeks and
      subsequently retrained for 8 weeks. During the detraining and retraining phase,
      subjects did not receive rhGH. The resistance programme included three sets of
      eight repetitions at 75% of one-repetition maximum (1-RM), three times per week,
      for 10 upper and lower body exercises. Dynamic muscle strength was assessed by
      the 1-RM method every 2 weeks for 44 weeks. Needle biopsies of vastus lateralis
      muscle were obtained from seven men. Muscle strength increased during initial
      training by 40.4 +/- 5.5% (mean +/- SEM), ranging from 26.0 +/- 5.0 to 83.9 +/-
      15.6%, depending on muscle group. Increased strength was accompanied by
      hypertrophy (P < 0.05) of type I (17.4 +/- 4.1%) and II (25.8 +/- 12.4%) muscle
      fibres. Of initial strength gains, only 29.9 +/- 5.2% was lost with detraining.
      However, type I and II fibre cross-sectional area reverted to pretraining values.
      After 8 weeks of retraining, muscle strength returned to trained values, but
      without a significant change in fibre morphology. The results indicate that
      elderly men lose some muscle strength following short-term detraining, but that
      only a brief period of retraining suffices to regain maximal strength. Reversal
      of fibre cross-sectional area with detraining, and only modest improvement with
      retraining, suggests that much of the retention in strength with detraining and
      reacquisition of lost strength with retraining reflects neural adaptation.

PMID- 9171972
TI  - Immunohistochemical localization of estrogen receptor in the normal canine female
      genital tract.
AB  - The distribution of estrogen receptor (ER) in the ovaries and uterus was studied
      throughout the estrous cycle in the bitch. The stage in the estrous cycle of 25
      dogs was assessed by gross and histologic appearance of the uterus and ovaries
      and blood steroid hormone values. Demonstration of ER was performed by an
      indirect immunohistochemical technique with monoclonal antibodies. ER was found
      as a red nuclear staining in the surface, crypt, and glandular epithelium; in
      endometrial stroma cells; and in smooth muscle cells of the tunica muscularis of
      the uterus. Total scores of ER-positive cells varied during the estrous cycle,
      with the highest scores in the early proliferative stage and the lowest scores in
      the early secretory stage of the estrous cycle. These results are in concordance
      with the observations in other animals and the human uterus. In the canine
      ovaries, positive staining for ER was present in surface epithelium and
      subsurface epithelial ingrowths, which is in contrast with negative staining of
      human ovaries. This study confirms the earlier hypothesis that the epithelial
      ingrowths in canine ovaries may be responsive to blood steroid hormones.

PMID- 9171973
TI  - Countercurrent transfer of 125I-LHRH in the perihypophyseal cavernous sinus
      carotid rete vascular complex, demonstrated on isolated pig heads perfused with
      autologous blood.
AB  - The objective of the study was to determine whether the local permeability of
      luteinizing hormone-releasing hormone (LHRH) from the venous blood of the
      perihypophyseal cavernous sinus into the arterial blood of the carotid rete,
      supplying the brain and hypophysis in gilts, depends on the day of the estrous
      cycle, as well as to determine whether this transfer exists when LH concentration
      in the blood is reduced (the experimental short-loop negative feedback for LH
      secretion after estradiol injection in ovariectomized gilts). Experiments were
      conducted on isolated gilt heads with necks, on chosen days of the estrous cycle
      (n = 40), and on previously ovariectomized gilts treated with estradiol benzoate
      (EB) (n = 5) or corn oil (n = 3). After exsanguination, the gilt heads with necks
      were disarticulated and about 30-45 min later were supplied with autologous,
      oxygenated, and heated blood at a stable blood flow and pressure through the left
      carotid artery for 30 min. 125I-LHRH was infused into both cavernous sinuses
      through the cannulated angularis oculi veins for 5 min. After 125I-LHRH infusion,
      radiolabeled LHRH was found (P < 0.001) in arterial blood taken from the carotid
      rete through the open right carotid artery in all animals used in the experiment:
      on Days 1-2 (six gilts), on Days 12-14 (seven gilts) of the estrous cycle, and in
      five ovariectomized gilts during negative feedback for LH surge (40 hr after EB).
      No significant radioactivity of 125I-LHRH was found in the arterial blood on Days
      3-5 (n = 6), 9-11 (n = 4), and 15-21 (n = 17) of the estrous cycle. A very low
      level of radioactivity was found in the ovariectomized control group after the
      injection of corn oil (n = 3). These results provide evidence for the
      permeability of LHRH from the venous to the arterial blood and its retrograde
      transport with the arterial blood to the hypophysis and brain, after the
      ovulation period (Days 1-2) and on Days 12-14 of the estrous cycle. This suggests
      that a close relationship exists between the day of the estrous cycle and LHRH
      permeability from the venous to the arterial blood in the perihypophyseal
      cavernous sinus-the carotid rete complex in gilts-and that this mechanism may be
      included in a short-loop feedback for LHRH secretion.

PMID- 9171974
TI  - Effect of tumor necrosis factor-alpha on progesterone production by granulosa
      cells in laying hens of different genetic lines.
AB  - In vitro progesterone production by granulosa cells in the presence or absence of
      human recombinant tumor necrosis factor-alpha (hrTNF-alpha) was measured at 10,
      20, and 30 wk of egg production in White Leghorn hens selected for high (HA)- or
      low-antibody (LA) response to sheep red blood cell challenge. Isolated granulosa
      cells from the three largest preovulatory follicles (F1-F3) were incubated with 5
      or 250 ng/ml hrTNF-alpha, and progesterone production was determined by the use
      of a validated radioimmunoassay. F1, F2 and F3 granulosa cells from HA hens
      produced more (P < or = 0.05) progesterone (140.8, 107.2, and 49.7 ng/ml) than LA
      hens (109.4, 78.9, and 26.9 ng/ml). The treatment of granulosa cells with hrTNF
      alpha consistently inhibited (P < or = 0.05) progesterone secretion by all
      follicles among HA and LA hens, but not always at both doses. Generally, 5 ng/ml
      hrTNF-alpha was the maximum inhibitory dose. In the laying hen, a decrease in
      steroid production in response to cytokines may upset the steroid balance created
      by follicular hierarchy and inhibit or delay ovulation.

PMID- 9171975
TI  - Effect of gonadotropin treatment on size, number, and cell proliferation of
      antral follicles in cows.
AB  - To determine the effects of gonadotropins on the size, number, and cell
      proliferation of antral ovarian follicles, cows received FSH-P or vehicle
      beginning on Day 2 after estrus, and ovaries were collected 6, 12, 24, or 48 hr
      after the initiation of FSH-P treatment or 24 or 48 hr after the initiation of
      vehicle treatment. Ovaries also were collected from untreated cows on Day 2 after
      estrus (pretreatment). Before fixation, all visible antral follicles were counted
      and their surface diameters were recorded. Proliferating cells were
      immunolocalized in fixed follicles by using a specific primary antibody against
      proliferating cell nuclear antigen (PCNA), and the labeling index (LI; percentage
      of cells staining positively for PCNA) was determined for granulosa and thecal
      cells. After 48 hr of treatment, FSH-P-treated cows had fewer (P < 0.01) small
      antral follicles and more medium and large antral follicles (P < 0.01 and P <
      0.05, respectively) compared with vehicle-treated cows. Granulosa cell LI was
      negatively correlated (P < 0.05) with follicular diameter for vehicle-treated but
      not for FSH-P-treated cows. Analysis of covariance using follicular diameter as a
      covariate to adjust to a common diameter indicated that granulosa cell LI was
      greater (P < 0.05) at 24 and 48 hr in FSH-P-treated than in vehicle-treated cows;
      conversely, thecal cell LI was greater (P < 0.01) at 48 hr in FSH-P-treated
      compared with vehicle-treated cows but did not differ at 24 hr. Across all
      groups, the LI of cells located within the antral half of the granulosa cell
      layer was greater (P < 0.01) than that of cells located within the basal half. In
      conclusion, the stimulation of follicular development by exogenous gonadotropins
      increased or maintained the proliferation of granulosa and thecal cells
      concomitant with continued follicular growth. Therefore, enhanced follicular cell
      proliferation may be an important mechanism by which FSH-P superinduces the
      growth of antral follicles in cows.

PMID- 9171976
TI  - Cellular mechanisms by which oxytocin stimulates uterine PGF2 alpha synthesis in
      bovine endometrium: roles of phospholipases C and A2.
AB  - The objective of these experiments was to identify the cellular mechanisms by
      which oxytocin stimulates prostaglandin (PG) F2 alpha synthesis in bovine
      endometrial tissue. Uteri were collected on the day after spontaneous luteal
      regression. Caruncular endometrial explants were dissected and incubated in vitro
      to assess PGF2 alpha release or phospholipase (PL) C activity. Oxytocin (10(-6)
      M) stimulated PGF2 alpha release and PLC activity within 30 min of incubation (P
      < 0.01). The highest stimulation was observed at 100 min (P < 0.01). Oxytocin
      stimulated PLC activity at 10(-9) M and higher doses, whereas an increase in PGF2
      alpha release was not detected until 10(-8) M (P < 0.09). Melittin, a stimulator
      of PLA2 activity, stimulated PGF2 alpha release at 10(-6) M and higher doses (P <
      0.01). Aristolochic acid, an inhibitor of PLA2 activity, blocked the ability of
      oxytocin to stimulate PGF2 alpha release at 10(-5) M and higher doses (P < 0.01).
      Aristolochic acid (10(-4) M) reduced the stimulation of PGF2 alpha release
      induced by A1F4-, a nonspecific stimulator of G protein (10(-5) M) and melittin
      (10(-4) M; P < 0.05). Aristolochic acid had no effect on the ability of oxytocin
      or A1F4- to stimulate PLC activity (P > 0.10). By comparing the time course of
      stimulation and dose-response relationships between PGF2 alpha and PLC activity,
      it appears that oxytocin may stimulate PGF2 alpha secretion by activating PLC.
      The effects of melittin and aristolochic acid indicate that PLA2 may play a role
      in mediating the stimulatory effect of oxytocin on PGF2 alpha secretion, as well.

PMID- 9171977
TI  - Lack of effect of granulocyte-macrophage colony-stimulating factor on secretion
      of interferon-tau, other proteins, and prostaglandin E2 by the bovine and ovine
      conceptus.
AB  - Three experiments tested the effects of recombinant bovine granulocyte-macrophage
      colony-stimulating factor (rbGM-CSF) on the preimplantation bovine and ovine
      conceptus. There was no effect of rbGM-CSF on the secretion of total radiolabeled
      protein in conditioned medium, immunoreactive interferon-tau (IFN tau), antiviral
      activity, or prostaglandin E2 from Day 16-18 bovine conceptuses cultured for 24
      hr with, [3H]leucine and +/- 10 ng/ml rbGM-CSF. Similarly, there was no effect of
      1 ng/ml rbGM-CSF on the secretion of total radiolabeled protein. IFN tau, or
      antiviral activity from Day 17 ovine conceptuses. There was also no beneficial
      effect of 1 or 10 ng/ml rbGM-CSF on the presence of immunoreactive IFN tau in
      conditioned medium from in vitro-produced bovine blastocysts at Day 7-8 after
      fertilization. Results indicate that IFN tau secretion from bovine and ovine
      conceptuses are unresponsive to rbGM-CSF at the concentrations tested.

PMID- 9171978
TI  - Green chemistry.

PMID- 9171979
TI  - Magico-religious mercury exposure.

PMID- 9171980
TI  - MMA:DMA ratios reversed.

PMID- 9171981
TI  - Reply to comments on "A reevaluation of cancer incidence near the Three Mile
      Island".

PMID- 9171983
TI  - Breast cancer and MCS in EHP.

PMID- 9171982
TI  - Too easily lead? Health effects of gasoline additives.
AB  - Octane-enhancing constituents of gasoline pose a number of health hazards. This
      paper considers the relative risks of metallic (lead, manganese), aromatic (e.g.,
      benzene), and oxygenated additives in both industrialized and developing
      countries. Technological advances, particularly in industrialized countries, have
      allowed the progressive removal of lead from gasoline and the increased control
      of exhaust emissions. The developing world, by contrast, has relatively lax
      environmental standards and faces serious public health problems from vehicle
      exhaust and the rapid increase in automobile use. Financial obstacles to the
      modernization of refineries and vehicle fleets compound this problem and the
      developing world continues to import large quantities of lead additives and other
      hazardous materials. Progress in decreasing environmental health problems depends
      both on the adoption of international public health standards as well as efforts
      to decrease dependence on the private automobile for urban transport.

PMID- 9171984
TI  - New dimensions to dementia.

PMID- 9171986
TI  - From the laboratory to the community: a commitment to outreach.

PMID- 9171987
TI  - New NTP bioassay results.

PMID- 9171988
TI  - Exposing ourselves to art.

PMID- 9171989
TI  - Germ warfare.

PMID- 9171990
TI  - Environmental xenobiotics may disrupt normal endocrine function by interfering
      with the binding of physiological ligands to steroid receptors and binding
      proteins.
AB  - The disruption of the reproductive system of male and female animals in the wild
      has been attributed to environmental chemicals (xenobiotics). The effects seen
      mirror alterations one might anticipate if the steroid hormone-dependent
      processes that regulate these systems were impaired. To determine whether
      xenobiotics (present at a concentration of 100 microM) exert their action through
      steroid-mediated pathways, we examined their ability to inhibit the binding of
      [3H]physiological ligands (present at a concentration of 7 nM) to the androgen
      and estrogen receptors, rat androgen-binding protein (ABP), and human sex hormone
      binding globulin (hSHBG). The gamma- and delta-isomers of hexachlorocyclohexane,
      congeners of dichlorodiphenyl-trichloroethane (DDT; p,p'-DDT; p,p'-DDE; o,p'
      DDT), dieldrin, atrazine, and pentachlorophenol, caused a statistically
      significant inhibition of specific binding of [3H]5 alpha-DHT to the androgen
      receptor that ranged from 100% (p,p'-DDE) to 25% (dieldrin). Methoxychlor, o,p'
      DDT1, pentachlorophenol, and nonylphenol significantly reduced [3H]17 beta
      estradiol binding to the estrogen receptor by 10, 60, 20, and 75%, respectively.
      The binding of [3H]5 alpha-DHT to ABP was inhibited 70% by the delta-isomer of
      hexachlorocyclohexane, but the gamma-isomer did not reduce binding significantly.
      Methoxychlor, p,p'-DDT, atrazine, and nonylphenol reduced [3H]5 alpha-DHT binding
      to ABP by approximately 40%. Nonylphenol reduced the binding of [3H]5 alpha-DHT
      to hSHBG by 70%. Hexachlorocyclohexane reduced [3H]5 alpha-DHT binding to hSHBG
      by 20%, but the stereospecific effects observed with ABP did not occur. o,p'-DDT
      and pentachlorophenol resulted in a statistically significant 20% inhibition of
      [3H]5 alpha-DHT binding to hSHBG. Some xenobiotics resulted in dissociation of
      [3H]ligands from their binding proteins that was statistically identical to that
      caused by the unlabeled natural ligand, whereas others resulted in slower or more
      rapid dissociation rates.

PMID- 9171991
TI  - Maternal smoking during pregnancy and postnatal exposure to environmental tobacco
      smoke as predisposition factors to acute respiratory infections.
AB  - This study compared susceptibility to respiratory morbidity in a cohort of 9-year
      old children exposed congenitally and postnatally to environmental tobacco smoke
      (ETS) to susceptibility in a cohort of unexposed children. The epidemiologic
      study included 1129 children: 594 boys and 535 girls attending the second grade
      of grammar schools in Krakow, Poland. We found strong evidence that children
      exposed to ETS in their homes were more susceptible to acute respiratory tract
      illnesses than unexposed children. A dose-response relationship between degree of
      exposure [for lower ETS exposure, odds ratio (OR) = 1.32; for higher ETS
      exposure, OR = 1.74] supports a causal explanation for the association observed.
      The significant trend of increased risk of respiratory infections due to ETS
      level in nonatopic children whose mothers did not smoke cigarettes during
      pregnancy suggests a direct effect of ETS exposure on the child's respiratory
      health. ETS combined with allergy nearly tripled the risk of acute respiratory
      tract illness (OR = 3.39; 95% CI, 1.93-5.93), and maternal smoking during
      pregnancy had a modifying effect on the risk of respiratory illnesses due to ETS
      after accounting for atopy. The stronger effect of ETS in atopic children and in
      those whose mothers smoked during pregnancy may be result of biologic interaction
      of endogenous and environmental factors. The results of this study are of
      relevance to public health policy, as children with higher risk of respiratory
      infections may be more susceptible to environmental hazards later in adolescence
      or in adulthood. Respiratory infections also increase demands for medical
      interventions in terms of outpatient services and hospital administrations. In
      addition, respiratory illnesses cause missed school days, and caring for a sick
      child may lead to absenteeism from work.

PMID- 9171993
TI  - Evaluation of the population distribution of dietary contaminant exposure in an
      Arctic population using Monte Carlo statistics.
AB  - Organochlorines and heavy metals have bioaccumulated in Arctic wildlife, which is
      an important food source for the Inuit. In this study, we have developed a
      statistical model to describe the population distribution of contaminant exposure
      and the usual intake of the high-end contaminant consumers. Monte Carlo methods
      are used to account for variations due to seasonal dietary pattern and
      contaminant concentrations. Distribution of the dietary intake of the
      contaminants of most concern-mercury, polychlorinated biphenyls (PCBs),
      chlordane, and toxaphenes-are described. Over 50% of the residents had dietary
      exposure levels exceeding the tolerable daily intake or provisional tolerable
      daily intake for Hg, toxaphene, and chlordane (83, 91, and 71% for men and 73,
      85, and 56% for women, respectively). The high-end consumers (i.e. the 95th
      centile) have intake levels 6 times higher than the provisional tolerable weekly
      intake of Hg, and over 20 times the tolerable daily intake of chlordane and
      toxaphene. Assessment of health risks of the relative high contaminant exposure
      in this community must also consider the nutritional, economical, cultural, and
      social importance of these traditional foods. A comprehensive risk management
      scheme has yet to be developed.

PMID- 9171992
TI  - Intrauterine growth retardation in Iowa communities with herbicide-contaminated
      drinking water supplies.
AB  - In a statewide survey of 856 Iowa municipal drinking water supplies in 1986-1987
      the Rathbun rural water system was found to contain elevated levels of triazine
      herbicides. Rates of low birth weight, prematurity, and intrauterine growth
      retardation (IUGR) in live singleton births during the period 1984-1990 by women
      living in 13 communities served by the Rathbun water system were compared to
      other communities of similar size in the same Iowa counties. The Rathbun
      communities had a greater risk of IUGR than southern Iowa communities with other
      surface sources of drinking water (relative risk = 1.8; 95% CI = 1.3, 2.7).
      Multiple linear regression analyses revealed that levels of the herbicides
      atrazine, metolachlor, and cyanzinc were each significant predictors of community
      IUGR rates in southern Iowa after controlling for several potentially confounding
      factors including maternal smoking and socioeconomic variables. The association
      with IUGR was strongest for atrazine, but all three herbicides were
      intercorrelated and the independent contributions of each to IUGR risk could not
      be determined. We conclude that communities in southern Iowa with drinking water
      supplies contaminated with herbicides have elevated rates of IUGR compared to
      neighboring communities with different water supplies. Because of the limitations
      of the ecologic design of this study, including aggregate rather than individual
      measures of exposure and limited ability to control for confounding factors
      related to source of drinking water and risk of IUGR, a strong causal
      relationship between any specific water contaminant and risk of IUGR cannot yet
      be inferred. The association between the water supplied to the Rathbun
      communities and the increased risk of IUGR should be considered a preliminary
      finding that needs to be verified by more detailed epidemiologic studies.

PMID- 9171994
TI  - Possible relevance of pigeons as an indicator species for monitoring air
      pollution.
AB  - Wild city pigeons were caught at four different locations in the Netherlands to
      represent areas of high (Amsterdam-high), moderate (Amsterdam-medium), and low
      (Maastricht and Assen) traffic density. It is assumed that local ambient air
      pollution decreases as a function of traffic density. In these pigeons levels of
      polycyclic aromatic hydrocarbon (PAH)-DNA adducts, oxidative DNA damage, and
      heavy metal residues were determined in kidney, lung, liver, and blood (no adduct
      analysis in blood). The contribution of leaded gasoline to total body lead
      content was estimated by measuring concentrations of Pb and its isotopes in
      blood. We also analyzed samples of ambient air particulate matter for PAH and
      heavy metal concentrations at the four different locations. Interregional
      differences in heavy metals in ambient air particulate matter were reflected
      relatively well by pigeon body loads. The higher lead and cadmium concentrations
      in blood, kidney, liver, and lung were found in the Amsterdam high traffic
      density area, followed by Amsterdam medium, Assen, and Maastricht. A high Pb
      concentration in blood coincided with relatively low 206Pb/207Pb values,
      indicating a high contribution of leaded gasoline to total blood Pb
      concentrations in pigeons from the Amsterdam high traffic density area.
      Significantly enhanced blood zinc values were found in pigeons from both
      locations in Amsterdam compared to pigeons from the other two areas. However, no
      differences in Zn tissue levels between the four different groups were found.
      Oxidative DNA damage, determined as the ratio of 7-Hydro-8-oxo-2'-deoxyguanosine/
      deoxyguanosine, in pigeon liver was highest in Amsterdam-high, followed by Assen
      (low traffic density). Pb content, but not the Cd content, was positively
      associated with oxidative DNA damage in liver tissue. In lung tissue, a negative
      correlation was found between oxidative DNA damage and Zn content. These results
      indicate that the carcinogenic potential of Pb might be ascribed to oxygen
      radical formation, whereas Zn plays a protective role against oxidative DNA
      damage. Places with high and medium traffic density could be clearly
      discriminated on the basis of PAH levels in the ambient air. The PAH content in
      particulate air samples was not, however, reflected in total PAH-related DNA
      adduct levels because no differences could be observed in tissue adduct levels in
      pigeons from the four different locations. Our results indicate that wild city
      pigeons can be used as biological indicators of exposure to heavy metal pollution
      in outdoor air.

PMID- 9171995
TI  - Ultraviolet radiation-induced immune modulation: potential consequences for
      infectious, allergic, and autoimmune disease.

PMID- 9171996
TI  - Involvement of multiple loci on chromosome 3 in renal cell cancer development.
AB  - In renal cell carcinoma (RCC), mostly occurring as sporadic cases, the short arm
      of chromosome 3 is a frequent target of deletion events. Taking into account
      cytological classifications of RCC, the deletions appear to be characteristic of
      clear cell or nonpapillary RCC only. This subtype constitutes most sporadic RCC
      and RCC as part of the Von Hippel-Lindau disease caused by germline mutations of
      VHL at 3p25. In a proportion of sporadic tumours, somatic mutations of VHL occur,
      again only in clear cell or nonpapillary RCC. However, in a sizable proportion of
      sporadic clear cell RCC, VHL mutations are absent. Therefore, a role for VHL in
      RCC development in general seems unlikely. Familial papillary RCC is not linked
      to chromosome 3. A rat model of hereditary RCC, the EKER rat, is associated with
      a germline mutation of the rat homologue of the tuberous sclerosis gene on human
      chromosome 16. Analysis of allelic losses of chromosome 3 in 143 highly
      informative sporadic tumours published in the literature points to a small
      segment of 3p21.3 as a candidate tumour-suppressor region. A 2-Mb fragment
      containing this segment suppresses tumourigenicity when present in mouse
      fibrosarcoma cells. A similar effect could be attributed to the region 3p12-p14
      on the basis of results from its introduction into an RCC cell line. The
      responsible gene should not be sought at 3p14 translocation breakpoints
      segregating with RCC in a few rare families because there is evidence that RCC in
      these cases is due to events involving VHL or another gene distal to the
      breakpoint. FHIT is also an unlikely candidate according to observations
      comparing RCC and a variety of normal tissues. Results of an analysis of sporadic
      patients with multiple renal tumours indicate an association of allelic losses of
      the VHL and 3p12-p14 regions with adenomas and suggest that losses of the 3p21
      region are necessary for malignant development to clear cell or nonpapillary RCC.

PMID- 9171997
TI  - Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic
      syndromes without cytogenetic evidence of 12p abnormalities.
AB  - Seventy-nine acute myeloid leukemias (AML) and myelodysplastic syndromes without
      cytogenetic evidence of 12p aberrations were investigated by fluorescence in situ
      hybridization with probes for ETV6 and CDKN1B (previously called TEL and KIP1,
      respectively) to ascertain whether abnormalities of these genes are frequently
      undetected by standard chromosome banding analyses and, if so, whether they are
      associated with specific karyotypic patterns and morphologic features. One of
      sixty cytogenetically aberrant myeloid malignancies, an AML with a complex
      karyotype including del(5q) and del(20q), showed a hemizygous interstitial
      deletion of the ETV6 and CDKN1B loci. No concomitant rearrangement of the other
      ETV6 allele was detected. Two of nineteen cytogenetically normal AML displayed a
      hemizygous interstitial deletion involving CDKN1B, but not ETV6. Thus, cryptic
      deletions of these genes seem to be rare in cytogenetically abnormal myeloid
      malignancies without 12p aberrations (2%), whereas they may be more frequent in
      karyotypically normal AML (10%). Furthermore, the present findings show that the
      deletions may be narrow, not including the ETV6 gene, and indirectly suggest that
      CDKN1B, or a closely located genomic segment, is the target of 12p deletions.

PMID- 9171998
TI  - Frequent homozygous deletion of cyclin-dependent kinase inhibitor 2 (MTS1, p16)
      in superficial bladder cancer detected by fluorescence in situ hybridization.
AB  - Deletion of all or part of chromosome 9 is a well-described genetic alteration in
      bladder tumors. It has been proposed that inactivation of a tumor-suppressor gene
      on chromosome 9 is an important event in tumor development. Recent reports have
      supported cyclin-dependent kinase inhibitor 2 (CDKN2, also known as MTS1, INK4,
      p16) at 9p21 as a candidate tumor-suppressor gene in solid tumors. However, the
      prevalence of CDKN2 mutations in primary bladder tumors has been controversial.
      Therefore, we applied gene-specific probes for CDKN2 and the interferon alpha
      gene (IFNA), also located at 9p21, to characterize further the genomic deletions
      at this locus in bladder cancer. Seventeen superficial (pTa or pT1) bladder tumor
      specimens were examined for gene deletion by fluorescence in situ hybridization.
      Dual-labeling hybridization with a repetitive pericentromeric probe for
      chromosome 9 and a gene-specific probe for CDKN2 was performed to characterize
      the gene copy number in relation to the chromosome 9 copy number on a cell-by
      cell basis. Homozygous deletion for CDKN2 without homozygous IFNA deletion was
      found in 5 of 17 tumors tested. Both genes were deleted in one additional case,
      and one tumor showed deletion of IFNA without deletion of CDKN2. Homozygous
      deletion at the 9p21 locus was found only in tumors having monosomy for the
      chromosome 9 centromeric signal. These results indicate that the homozygous
      deletion of the CDKN2 gene is a frequent and early event in superficial bladder
      cancer.

PMID- 9171999
TI  - Deletional, mutational, and methylation analyses of CDKN2 (p16/MTS1) in primary
      and metastatic prostate cancer.
AB  - The tumor suppressor gene CDKN2 (p16/MTS1) resides on chromosome 9p21 and encodes
      a 16 kDa inhibitor of the cyclin-dependent kinases. Inactivation of CDKN2 by
      homozygous deletion, point mutation, and recently described aberrant methylation
      in the 5' promoter region may increase progression through the cell cycle in
      tumors. In this study, we examine the CDKN2 gene for the presence of inactivating
      alterations in human prostate cancer. Sequence analysis of cell lines revealed no
      mutation in LNCaP, PC3, and TSU-PR1 and a missense mutation, GAC-->TAC (asp to
      tyr), in exon 2 of the DU145 cell line at codon 76. No mutations were identified
      in three primary prostate cancers or in seven lymph node metastases. Loss of
      heterozygosity (LOH) was analyzed by analysis of microsatellite markers in the
      vicinity of the CDKN2 gene. LOH was detected in 12 (20%) of 60 primary tumors at
      one or more loci and in 13 (46%) of 28 metastases. Methylation analysis of the
      CpG-rich promoter region revealed a dense methylation of CDKN2 in cell lines PC3,
      PPC1, and TSU-PR1, and this was found to correlate with a lack of mRNA expression
      by reverse transcription-polymerase chain reaction. A demethylating agent, 5-aza
      2'-deoxycytidine, induced reexpression when cells were exposed in vitro. DU145
      and LNCaP expressed the CDKN2 transcript and were unmethylated in the promoter
      region. Three of twenty-four (13%) primary prostate cancers and 1 of 12
      metastatic tumors demonstrated promoter methylation. No normal prostate tissues
      were methylated at the CDKN2 gene promoter. One tumor was found to contain
      concomitant LOH and promoter methylation indicative of biallelic inactivation. A
      comprehensive analysis of CDKN2 in prostate cancer reveals that point mutations
      are infrequent, but gene deletion and methylation combine to inactivate CDKN2 in
      a subset of tumors. Moreover, alterations in this gene may represent a late event
      in prostate cancer progression.

PMID- 9172000
TI  - Identification of genes with specific expression in pancreatic cancer by cDNA
      representational difference analysis.
AB  - cDNA representational difference analysis (cDNA-RDA) is a polymerase-chain
      reaction-coupled subtractive and kinetic enrichment procedure for the isolation
      of differentially expressed genes. In this study, the technique was used to
      isolate novel genes specifically expressed in pancreatic cancer. cDNA-RDA was
      done on cDNA reverse transcribed from a poly(A)+ mRNA pool made from 10 cancer
      tissues (tester) by using as a driver a cDNA from a poly(A)+ mRNA pool made from
      a combination of 10 tissues of chronic pancreatitis and 10 healthy pancreatic
      tissues. The use of chronic pancreatitis in addition to healthy pancreas mRNA in
      the driver preparation eliminated the influence of stromal tissue components
      present as contamination in the cancer-specific preparations. Such cDNA-RDA led
      to the isolation of 16 distinct, cancer-specific gene fragments. These were
      confirmed to be overexpressed in pancreatic cancer tissues by Northern blot
      analysis. Sequence analysis revealed homologies to five genes previously
      implicated in the carcinogenesis of the pancreas or other tissues. Eleven
      fragments had no significant homology to any known gene and thus represent novel
      candidate disease genes. The experiments demonstrate that cDNA-RDA is a
      reproducible and highly efficient method for the identification of novel genes
      with cancer-specific expression.

PMID- 9172001
TI  - DNA copy number changes associated with characteristic LOH in islet cell
      carcinomas of transgenic mice.
AB  - Comparative genomic hybridization (CGH) provides a method of surveying the entire
      tumor genome for regional variations in DNA sequence copy number. Such
      variations, if found recurrently, may indicate the locations of genes that
      contribute to tumor development through upregulation of oncogenes (copy number
      increase), inactivation of tumor-suppressor genes (copy number decrease), or
      changes in the level of expression through gene dosage effects. Thus, CGH is a
      powerful tool for screening for new cancer genes. Although CGH is widely applied
      to human genome analysis, application to the mouse is only beginning. The present
      study is designed to compare results obtained by CGH with those obtained by other
      techniques used for analysis of the murine genome. We report CGH analysis of
      several control cell lines with cytogenetically established regional copy number
      changes, as well as analysis of 16 primary insulinomas, four tumor-derived cell
      lines, and three hyperplasia-derived cell lines from transgenic mice expressing
      the SV40 large T antigen under control of the rat insulin promoter. Loss of
      heterozygosity (LOH) on chromosomes 9 and 16 had previously been found to be
      frequent in primary insulinomas, and specimens were selected for the present
      study based on the LOH status of these chromosomes. We found complete concordance
      of the CGH results with the cytogenetically described copy number changes in the
      control cell lines and with the LOH on chromosomes 9 and 16 in the tumors. Thus,
      CGH can provide accurate data in murine systems, and it reveals that the LOH in
      these islet cell tumors most frequently results from deletion of one of the
      alleles.

PMID- 9172002
TI  - Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce
      structurally different thyroid-specific TRK oncogenes.
AB  - The NTRK1 gene in the q arm of chromosome 1 encodes one of the receptors for the
      nerve growth factor and is frequently activated as an oncogene in papillary
      thyroid carcinomas. The activation is due to chromosomal rearrangements
      juxtaposing the NTRK1 tyrosine kinase domain to 5'-end sequences from different
      genes. The thyroid TRK oncogenes are activated by recombination with at least
      three different genes: the gene coding for tropomyosin and TPR, both on
      chromosome 1,and TFG on chromosome 3. In a previous study, we showed that two
      tumors carrying the TPR/NTRK1 rearrangement contained structurally different
      oncogenes named TRK-T1 and TRK-T2. In this paper, we report (1) the cDNA
      structure of TRK-T2, (2) evidence that TRK-T2 is generated by different
      rearrangements in two thyroid tumors, and (3) a detailed analysis of the three
      different TPR/NTRK1 rearrangements. With molecular studies based on Southern blot
      hybridization, cloning, and sequencing, we show that all the rearrangements are
      nearly balanced, involving deletion, insertion, or duplication of only few
      nucleotides. In one case, an additional rearrangement involving sequences derived
      from chromosome 17 was detected.

PMID- 9172003
TI  - Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia
      measured using comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) was used to identify recurrent regions of
      DNA sequence loss and gain in 21 multiple myeloma (MM) and plasma cell leukemia
      (PCL) primary tumor specimens and cell lines. Multiple regions of non-random
      sequence loss and gain were observed in 8/8 primary advanced stage tumors and
      13/13 cell lines. Identification of sequence copy number changes was facilitated
      by statistical analyses that reduce subjectivity associated with identification
      of copy number changes and by requiring that sequence changes are visible using
      both red- and green-labeled tumor DNA. Loss of sequence on 13q and 14q and gain
      of sequence on 1q and chromosome 7 occurred in 50-60% of the population. In
      general, cell lines carry more and larger regions of sequence gain and loss than
      primary tumors. Regions of sequence copy number change that recur among MM cell
      lines and primary tumors include, in order of prevalence, enh(1q12qter), dim(13),
      enh(7), enh(3q22q29), enh(11q13.3qter), dim(14q11.2q31), enh(8q21qter),
      enh(3p25pter), dim(17p11.2p13), and dim(6q22.1q23). Population distributions of
      genome-wide changes in primary tumors reveal "hot-spots" of sequence loss from
      13q12.1-q21, 13q32-q34, 14q11.2-q13, and 14q23-q31. Genomic changes detected
      using CGH are consistent with those identified using banding analyses, although
      recurrent involvement of additional regions of the genome are also evident. A
      higher prevalence of genomic changes is visible using CGH compared to banding.
      Identification of recurrent regions of sequence gain and loss provides
      opportunities to identify regions of the genome that may be involved in the
      malignant phenotype and/or disease progression.

PMID- 9172004
TI  - Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after red wine
      oral administration in rats.
AB  - Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene), a natural
      compound from grape products, have been evaluated in rats after oral
      administration of red wine. Resveratrol concentrations were measured in plasma,
      heart, liver and kidneys. Tissue concentrations showed a significant cardiac
      bioavailability and strong affinity for liver and kidneys.

PMID- 9172005
TI  - Determination of bioequivalence of two furosemide preparations; the effect of
      high doses of furosemide on some pharmacokinetic parameters.
AB  - The bioequivalence of two oral preparations of the diuretic furosemide, namely
      (i) a Croatian pharmaceutical product (test preparation A) and (ii) a reference
      preparation B, both in a dose of 500 mg was assessed in an open, cross-over,
      randomized trial in 15 healthy male volunteers, in whom the HPLC method with a
      fluorescent detector was used to determine its concentrations. The test
      preparation (A) was found to achieve a considerably higher concentration (17.2 +/
      9.304 mg/l) than the reference preparation (11.1 +/- 6.484 mg/l); the time to
      peak concentrations was statistically significantly shorter for the test
      preparation (1.033 +/- 0.743 h) than for the reference preparation (1.656 +/-
      0.586), and the areas under the concentration curves were statistically
      significantly greater for the examined preparation (65.9 mg.h/l) than for the
      reference preparation (46.845 mg.h/l). The relative bioavailability of the test
      preparation was 129%, i.e. it was not bioequivalent with the reference
      preparation. This finding was consistent with the previously performed laboratory
      quality testing in vitro, where the release of the reference preparation was
      found to be considerably slower and weaker than that of the test preparation.
      High doses of furosemide exemplified by 500 mg were found to affect only some of
      the pharmacokinetic parameters, i.e. they induce an accelerated absorption, an
      increase in serum concentration, and a prolongation of its half-life.

PMID- 9172006
TI  - Prediction of blood cyclosporine concentrations in haematological patients with
      multidrug resistance by means of total, lean and different adipose factors dosing
      body weight using Bayesian and non-linear least squares methods.
AB  - In the present work, we have studied the prediction of blood cyclosporine (CsA)
      concentrations in haematological patients with multidrug resistance by means of
      total body weight, 25, 50 and 75 adipose factor dosing body weight, and lean body
      weight using the Bayesian method (BM) and non-linear least squares method (NLLSM)
      during the second course of CsA treatment. The results showed that both BM and
      NLLSM can minimize the prediction difference among different dosing body weight
      parameter types. The results also slightly favour the predictions with lean body
      weight.

PMID- 9172007
TI  - Effect of beraprost sodium, a stable prostaglandin I2 analogue, on platelet
      aggregation in diabetes mellitus.
AB  - Test results concerning platelet behavior in vitro, particularly aggregation, are
      frequently abnormal in diabetic patients. The concept has therefore arisen that
      platelet hyper-reactivity is one factor contributing to diabetic microangiopathy.
      We report here the antiplatelet effect of beraprost sodium, a chemically stable
      prostaglandin I2 analogue made in Japan, in 6 diabetic patients. Platelet
      aggregation induced by adenosine 5'-diphosphate (10 microM) after administration
      of beraprost sodium (40 micrograms every 8 h for 14 days) was significantly
      decreased as compared with levels before beraprost sodium administration. These
      results indicate the possibility that the occurrence of vascular complications in
      diabetes mellitus can be suppressed by long-term administration of beraprost
      sodium.

PMID- 9172008
TI  - Azithromycin in the treatment of pneumonias caused by Chlamydia spp: a
      retrospective study.
AB  - A retrospective study was undertaken in order to compare the efficacy and safety
      of azithromycin and doxycycline in the treatment of pneumonias caused by
      Chlamydia spp. Patients with radiologically confirmed pneumonia and positive
      complement fixation test for chlamydial infection who were hospitalized in the
      University Hospital of Infectious Diseases, Zagreb during the years 1989-1992
      were reviewed. Among them, 83 were treated with azithromycin, given in a total
      dose of 1.5 g over 5 days (500 mg once daily at day 1 followed by 250 mg at days
      2-5, 60 patients) or 3 days (500 mg once daily, 23 patients). Twenty-two patients
      were treated with doxycycline (100 mg b.i.d. for 10 days). Treatment groups were
      comparable with respect to age, sex, and severity of signs and symptoms of
      illness. All the patients were cured. There were no differences in duration of
      fever after treatment initiation between patients treated with azithromycin
      (whether pretreated with beta-lactam antibiotics or not) and doxycycline (p >
      0.05). In addition, 3- and 5-day azithromycin courses were equally effective (p >
      0.05). Both drugs were well tolerated, and only two patients treated with
      azithromycin reported nausea. It may be concluded that in the treatment of
      pneumonias caused by Chlamydia spp. azithromycin is as effective and well
      tolerated as doxycycline.

PMID- 9172009
TI  - Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial.
AB  - In this multicentre trial tramadol and buprenorphine were compared for the
      treatment of neoplastic pain no longer responsive to non-steroidal
      antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with
      tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one
      sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six
      months. Most patients started treatment with 2-3 tablets/day in both groups, and
      the mean treatment period was 58 days for tramadol and 51 for buprenorphine.
      Almost all dose changes needed were made in the first fortnight in both treatment
      groups, and the largest number of patients dropped out because of inadequate pain
      relief or progression of the underlying disease. The results achieved in the
      first two weeks persisted throughout the rest of the trial, and the
      investigator's assessments on each patient's clinical chart corresponded closely
      with those that patients made in their own daily diaries. In the four hours after
      the first dose both drugs virtually halved the severity of pain (measured using a
      visual analogue scale), and this relief lasted throughout treatment. By the end
      of the first week the proportion of patients with strong/unbearable pain in the
      tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as
      compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also
      tended to improve in the tramadol group, with the proportion of patients enjoying
      good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with
      buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life
      did not change in the tramadol group; in the buprenorphine group the Karnofsky
      index dropped slightly after a fortnight (p < 0.05 between treatments). In the
      first two months of the trial the number of patients with no/moderate pain rose
      continuously in the tramadol group (71% and 80% after one and two months); the
      rise was less marked in the buprenorphine group (number of patients with
      mild/moderate pain, 45% and 65%). In both the short term and in the longer term,
      it was found that the levels of efficacy and acceptability were always
      significantly better in the tramadol group than in the buprenorphine group.
      General and biological safety in both drugs was good. The most typical side
      effects were those characteristic of opioids (nausea and/or vomiting,
      drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%)
      and in 16 taking buprenorphine (26%). There were six drop-outs in the first group
      (9%) and seven in the second (11%). Serious symptoms arose more frequently in the
      buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were
      noted.

PMID- 9172011
TI  - Ricin toxin contains three lectin sites which contribute to its in vivo toxicity.
AB  - Ricin intoxication of mammalian cells is initiated by B chain (RTB) binding to
      cell surface galactosides. Recombinant insect-derived RTB mutants with
      modifications in lectin-site subdomains 2 gamma, 1 alpha/2 gamma, and 1 alpha/1
      beta/2 gamma were reassociated with plant RTA and tested for lethality in C57B1/6
      6-8 weeks old mice. The LD50 of intraperitoneally injected castor bean ricin was
      75 ng per 18 g mouse. The LD50 of single-site 2 gamma mutant heterodimer was 100
      ng: the LD50 of the double-site 1 alpha/2 gamma mutant heterodimer was 500 ng,
      and the LD50 of the triple-site 1 alpha/1 beta,2 gamma mutant heterodimer was >
      10 micrograms. Plant RTA alone had an LD50 of 300 micrograms. Animals died
      between 1 and 10 days post-injection. Histopathological examination of morbid
      animals receiving an LD50 dose of each toxin revealed only apoptosis in the
      thymus and spleen. The present data provide clear evidence for participation of
      three lectin sites in ricin in vivo toxicity. These results suggest an origin for
      some of the normal tissue toxicities observed with clinical trials of doubly
      blocked ricin conjugates and suggest modification of at least three RTB
      subdomains will be necessary in genetically engineered ricin fusion proteins.

PMID- 9172010
TI  - Dexamethasone modulates CD2 expression.
AB  - Glucocorticoid hormones (GCs) are able to modulate leukocyte activity. We studied
      the effect of dexamethasone (DEX) on the expression of CD2, an adhesion molecule
      involved in T-lymphocyte homing and activation. Results of flow cytometry
      analysis and immunoprecipitation with anti-CD2 monoclonal antibodies (mAbs)
      indicated that in vitro treatment with DEX augments CD2 expression in transformed
      T-cell lines. This effect correlated with a rapid increase in the mRNA and was
      inhibited by actinomycin-D (AD). The DEX-induced CD2 augmentation was transient,
      peaked at days 1-2 and returned to the levels of untreated controls at days 3-4.
      It was a dose-dependent phenomenon, mediated by the GC receptor (GCR), because it
      was inhibited by the GCR antagonist RU486, and was not induced by other steroids
      such as testosterone and progesterone. This CD2 modulation could presumably
      contribute to GC-induced effects on T-cell activity.

PMID- 9172012
TI  - beta-Sitosterol and beta-sitosterol glucoside stimulate human peripheral blood
      lymphocyte proliferation: implications for their use as an immunomodulatory
      vitamin combination.
AB  - The phytosterols, beta-sitosterol (BSS), and its glucoside (BSSG) enhance the in
      vitro proliferative response of T-cells stimulated by sub-optimal concentrations
      of phytohaemagglutinin (PHA) several fold at extremely low concentrations
      (femtogram level). A 100:1 (mass:mass) ratio of BSS:BSSG (termed essential
      sterolin formulation, ESF) showed higher stimulation than the individual sterols
      at the same concentration. In vivo activity of ESF was also demonstrated when
      volunteers ingested ESF for 4 weeks. Proliferation of their T-cells, stimulated
      maximally with PHA, was significantly enhanced (20-920%) when compared to
      baseline values. In vitro, ESF (1 microgram.ml) was able to significantly enhance
      the expression of CD25 and HLA-Dr activation antigens on T-cells and increased
      the secretion, into the medium, of IL-2 and gamma interferon. NK-cell activity
      was also increased by BSS and BSSG alone, but with EST a higher activity was
      always found at different effector:target ratios (100:1 12:1).

PMID- 9172013
TI  - Heat-killed Bacillus subtilis inhibits T-cell proliferative response to mitogens
      and recall antigens.
AB  - Heat-killed vegetative forms of Bacillus subtilis were found to impair
      considerably the capacity of human T-lymphocytes to secrete interleukin-2 (IL-2)
      and to proliferate (in terms of [3H]thymidine incorporation) after
      phytohaemagglutinin (PHA) stimulation. B. subtilis was also found to interfere
      with T-cell proliferation induced by concanavalin A (Con A) and the recall
      antigen tetanus toxoid (TT). The suppressive activity was dependent on bacterial
      concentration, and was not ascribed to mitogen, medium-nutrient absorption or
      cell killing. Moreover, B. subtilis did not interfere with mitogen-induced IL-2
      receptor expression on the T-cell surface. On the other hand, B. subtilis did not
      interfere with T-cell proliferation induced by phorbol myristate acetate (PMA)
      and ionomycin stimulation. All data obtained suggest the binding of B. subtilis
      subcomponents to- or very close to-the T-cell receptor (TCR). Identification and
      purification of the basic structure(s) or component(s) of B. subtilis with TCR
      antagonist activity in vitro will help to exploit different aspects of T-cell
      activity and development, and possibly, will provide a means of specific control
      or modification of the immune response.

PMID- 9172015
TI  - (+/-)-3-[4-(2-dimethylamino-1-methylethoxy)-phenyl]-1H-pyrazolo[3,4- B]pyridine-1
      acetic acid (Y-25510) stimulates production of IL-1 beta and IL-6 at the level of
      messenger RNA expression in cultured human monocytes.
AB  - (+/-)-3-[4-(2-Dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3, 4-b]pyridine-1
      acetic acid (Y-25510) stimulated the mRNA expression for interleukin-1 beta (IL-1
      beta), and enhanced the expression induced by lipopolysaccharide (LPS) in
      cultured human peripheral blood mononuclear cells (PBMC) and THP-1 cells, a cell
      line derived from human monocytic leukemia. Y-25510 also stimulated the mRNA
      expression for IL-6 in both types of the cells, however, the stimulation required
      the presence of LPS. In THP-1 cells, the stimulation of IL-1 beta mRNA expression
      by Y-25510 was suppressed by cycloheximide, an inhibitor of protein synthesis.
      This phenomenon indicates that the stimulation requires de norv protein
      synthesis. In contrast, the stimulation of mRNA expression for IL-6 by Y-25510
      was not suppressed by cycloheximide but suppressed by N alpha-p-tosyl-L
      phenylalanine chloromethyl ketone (TPCK), an inhibitor of nuclear transcription
      factor-kappa B (NF-kappa B) activation, in the presence of LPS, suggesting that
      the stimulation requires NF-kappa activation. These results demonstrate that Y
      25510 stimulates the mRNA expression for IL-1 beta and IL-6 by different
      mechanisms. Dexamethasone suppressed the LPS-induced expression of mRNA for IL-1
      beta and IL-6 in THP-1 cells, whereas the drug never suppressed the mRNA
      expression for these cytokines in the presence of Y-25510. The result indicates
      that Y-25510 stimulates the mRNA expression for IL-1 beta and IL-6 by different
      mechanisms from those of LPS.

PMID- 9172014
TI  - Efficacy of an antipathology vaccine in murine schistosomiasis administered with
      and without chemotherapy.
AB  - This study was undertaken to study the efficacy of praziquantel (PZQ) in
      potentially tolerized Schistosoma mansoni infected, egg-injected C57BL/6 mice,
      receiving multiple administrations of soluble egg antigen (SEA) intravenously
      (i.v.). Four animal groups were studied. Experimental group I received four
      injections of SEA (10 micrograms) intravenously on days -7, -5, -3 and -2 before
      infection and PZQ orally (500 mg/kg over two consecutive days 7 weeks post
      infection. Three control groups received the following treatment: group II
      received the same tolerizing dose of SEA without PZQ, group III received PZQ in
      the same dose and at the same timing. Group IV received S. mansoni infection and
      egg injection 8 weeks post-infection and served as an infected, egg-injected
      control. Egg injection was conducted 8 weeks post-infection using viable S.
      mansoni eggs via the tail vein. Animals were killed 16 days post-egg injection,
      i.e. 10 weeks post-infection. After sacrifice, lungs and livers were removed for
      histopathological study and measurement of granuloma diameters. Spleens and serum
      were collected for the assay of lymphoproliferative response to SEA and
      antischistosomal immunoglobulins. The worm and egg burdens were also studied.
      Compared to infected, egg-injected untreated controls, repeated i.v.
      administrations of SEA down-regulated egg-injected (pulmonary) and egg-deposited
      (hepatic) granulomas and the lymphoproliferative response to SEA.
      Antischistosomal IgG level was increased. Susceptibility to S. mansoni infection
      was not found to be different from that in the infected, egg-injected controls.
      PZQ in the dose used caused complete eradication of worms, disappearance of
      immature egg stages, decrease in the number of mature eggs and an increase in the
      number of dead eggs. Hepatic granuloma diameter, lymphoproliferative response to
      SEA and IgG level were reduced. In mice receiving a combined regimen of multiple
      SEA administrations and PZQ with down-regulated granuloma and reduced
      lymphoproliferative response to SEA, the efficacy of PZQ was the same as in mice
      receiving PZQ alone. This was shown by comparable grades of worm and egg
      reduction. The histopathological examination of liver and lung sections in the
      different treated groups revealed moderate to small-sized hypocellular
      granulomas. Although no statistically significant difference was recorded between
      the mean granuloma diameters of the experimental group receiving both the
      tolerizing dose of SEA and PZQ compared to the group receiving the tolerizing
      dose of SEA without chemotherapy, this experimental group showed the least
      associated histopathological parenchymal changes. It appears from this work that
      combined SEA and PZQ provided many complementary goals; a reduction of egg
      induced pathology, minimal parenchymal changes and the eradication of worms.

PMID- 9172016
TI  - Bacterial expression and characterization of an anti-desipramine single-chain
      antibody fragment.
AB  - Tricyclic antidepressant toxicity is a leading cause of death from intentional
      drug overdose. Monoclonal antibody Fab' fragments specific for the tricyclic
      antidepressant, desipramine, reverse acute drug toxicity but may themselves have
      adverse effects at therapeutic doses. To evaluate the characteristics of smaller
      antibody fragments, we cloned, expressed and characterized a 26 kD single chain
      Fv fragment (G5-sFv). A DNA sequence encoding VH-linker-V1 was constructed from
      hybridoma mRNA encoding a high affinity monoclonal desipramine specific IgG1 and
      expressed in E. coli. G5-sFv was produced at high levels as insoluble inclusion
      bodies. Single chain Fv was solubilized, folded in a redox buffer and affinity
      purified on desipramine-Sepharose. The affinity of G5-sFv for desipramine was
      similar to that of the corresponding monoclonal Fab' as measured by surface
      plasmon resonance (Fab' 5.5 +/- 0.5 x 10(8) M-1, sFv 2.3 +/- 0.5 x 10(8) M-1). G5
      sFv administered to rats after a tracer dose of 3H-desipramine produced rapid and
      marked redistribution of drug from tissues into serum. G5-sFv was stable at 4 C
      for greater than 6 months but lost activity at higher temperatures. We conclude
      that desipramine-specific-single chain Fv expressed in E. coli retains the
      affinity of the parent antibody for desipramine. The pharmacokinetic effect of G5
      sFv on desipramine distribution suggests that it may be useful as an antidote for
      desipramine overdose.

PMID- 9172017
TI  - Differential regulation of TNF alpha, IL-1 beta, IL-6, IL-8, TNF beta, and IL-10
      by pentoxifylline.
AB  - Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of
      tumor necrosis factor-alpha (TNF alpha), which plays a key role in inflammation.
      Recent studies also revealed that other cytokines may be inhibited by PTX. We
      investigated PTX effects on production and mRNA expression of TNF alpha, IL-1
      beta, IL-6, IL-8, TNF beta and IL-10. Cytokine release was studied in 1/10
      diluted whole blood culture (WB) and in peripheral blood mononuclear cell (PBMC)
      culture. Cytokine production was triggered in both culture systems by endotoxin
      (LPS) or by phorbol ester (PMA) plus phytohemagglutinin (PHA). Our results showed
      that expression and production of TNF alpha and TNF beta were inhibited by PTX in
      a dose-dependent manner. Moreover, we observed that depending on the way of
      activating cells, PTX induced an up- or a down-regulation (in PMA + PHA or LPS
      stimulated cells, respectively) for IL-1 and IL-6 release. We also noted that the
      effects of PTX on IL-6, IL-8 and IL-10 production were different in WB and in
      PBMC culture. In conclusion PTX acts on cytokine in a complex manner depending on
      cellular environment and on the method of activation.

PMID- 9172018
TI  - Inhibition of macrophage nitric oxide production by tetrahydrocannabinol in vivo
      and in vitro.
AB  - delta 9-Tetrahydrocannabinol (THC, 10 micrograms) was administered
      intraperitoneally to thioglycollate-treated mice. After 18 h, peritoneal
      macrophages were harvested and nitric oxide (NO.) production was induced by
      lipopolysaccharide (LPS, 1 microgram/ml) and interferon-gamma (IFN-gamma, 0.1-10
      U/ml). Macrophages from THC-treated mice produced about half as much NO. as
      controls. THC (1 microgram/ml) added in vitro caused further inhibition. Greater
      inhibition was observed at the lower (0.1-0.3 U/ml) IFN-gamma concentrations. The
      results suggest that the use of THC can reduce NO. production and thereby affect
      host defense mechanisms, inflammation and autoimmune responses.

PMID- 9172019
TI  - Possible immunomodulating activities of carotenoids in in vitro cell culture
      experiments.
AB  - Immunomodulating activities of beta-carotene and carotene-associated carotenoids
      such as canthaxanthin (beta, beta-carotene-4,4 dione) and astaxanthin (3,3'
      dihydroxyl beta, beta-carotene 4,4-dione) were analyzed by in vitro cell culture
      experiments. (i) beta-Carotene, canthaxanthin and astaxanthin caused significant
      stimulatory effects on the cell proliferative response of spleen cells and
      thymocytes from BALB/c mice at the concentrations of 2 x 10(-8) to 10(-7) M,
      although they showed the activities different from each other. (ii) Astaxanthin
      exhibited the highest activity on the polyclonal antibody (immunoglobulin M and
      G) production of murine spleen cells at the concentrations of 2 x 10(-8) to 10(
      7) M but beta-carotene did not cause a significant effect at a low concentration
      (2 x 10(-8) M) although stimulated at a high concentration (2 x 10(-7) M).
      Canthaxanthin expressed moderate activities at the same concentrations. (iii) All
      tested carotenoids significantly enhanced the release of interleukin-1 alpha and
      tumor necrosis factor-alpha from murine peritoneal adherent cells at the
      concentrations of 2 x 10(-8) to 10(-7) M and the ranks of cytokine-inducing
      activities were astaxanthin > canthaxanthin > beta-carotene. These results
      indicate that carotenoids such as beta-carotene, canthaxanthin and astaxanthin
      have possible immunomodulating activities to enhance the proliferation and
      functions of murine immunocompetent cells.

PMID- 9172020
TI  - The influence of organic acids on the proliferation of human peripheral
      lymphocytes activated by concanavalin A and pokeweed mitogen.
AB  - The present study was undertaken to assess the influence of 25 organic acids,
      which appear in high concentrations in tissues of patients with various organic
      acidaemias, on the proliferation of human peripheral lymphocytes stimulated with
      concanavalin A (Con A) (a T-cell activator) and pokeweed mitogen (PWM)
      (predominantly a B-cell activator). Mononuclear cells were cultivated in flat
      bottomed 96-well microplates at 37 degrees C for 96 (Con A) or 144 h (PWM) in the
      presence of one mitogen at different concentrations and of one acid at doses
      ranging from 1 to 5 mM. Control cultures did not contain any acid. Cell
      reactivity was measured by the incorporation of tritiated thymidine into cellular
      DNA. We observed that, among the 25 acids tested, aminoadipic (AAD), 2-hydroxy-3
      methylvaleric (HMV), 2-ketoisocaproic (KIC), 2-methylbutyric (MBA), propionic
      (PPA) and tiglic (TIG) acids strongly suppressed lymphocyte DNA synthesis in Con
      A-supplemented cultures, whereas in cultures stimulated with PWM, 2
      ketoisovaleric (KIV) and PPA acids presented the same effect. In contrast, lactic
      (LAC) and pyruvic (PYR) acids activated lymphocyte DNA synthesis in cultures
      treated with Con A, the same effect occurring with LAC acid for PWM-stimulated
      lymphocytes. The most inhibitory or stimulatory acids were added to cultures at
      different times after the beginning of the incubation period when mitogens were
      added. Except for HMV, KIC, PPA and LAC acids, whose actions persisted even after
      24 h from the beginning of culture, the others only exerted their effects when
      added at time zero. The present study therefore demonstrated that some organic
      acids modulate DNA synthesis in Con A- and PWM-stimulated human lymphocytes.

PMID- 9172021
TI  - Postoperative analgesia with parenteral opioids: does continuous delivery
      utilizing a transdermal opioid preparation affect analgesic efficacy or patient
      safety?
AB  - STUDY OBJECTIVES: To compare, in patients who underwent major orthopedic surgical
      procedures, the efficacy of intravenous (IV) patient-controlled analgesia (PCA)
      with morphine combined with continuous administration of two doses of fentanyl or
      placebo via transdermal therapeutic system with fentanyl (TTSF) patches. DESIGN:
      Randomized, double-blind, placebo-controlled study. SETTING: University teaching
      hospital. PATIENTS: 62 patients aged 18 to 65 years, presenting for elective
      orthopedic surgery and general anesthesia. INTERVENTIONS: Patients were
      randomized to one of three groups: group 1 received two placebo patches; group 2
      received a 20 cm2 active patch delivering 50 micrograms/hr of fentanyl and a 30
      cm2 placebo patch; group 3 received a 30 cm2 active patch delivering 75
      micrograms/hr of fentanyl and a 20 cm2 placebo patch. All patches were placed
      approximately two hours prior to induction of general anesthesia. General
      anesthesia was induced with thiopental, intubation facilitated by the use of
      vecuronium or pancuronium, and anesthesia was maintained with isoflurane in an
      oxygen/nitrous oxide mixture (O2/N2O). Following surgery, IV morphine was
      provided using IV PCA with 1.5 mg of morphine with a 6-minute lockout and a 4
      hour maximum dosage of 30 mg. MEASUREMENTS AND MAIN RESULTS: The time and dosage
      of morphine administered was recorded. Vital signs, pain intensity at rest, level
      of sedation, and arterial oxygen saturation (SpO2) were measured at intervals
      throughout the 72-hour study period and at 6 and 12 hours following patch
      removal. The presence of side effects was noted. Visual analog pain scores
      throughout the 72 hours of the study were not significantly different among
      groups. Patients receiving active TTSF required less IV PCA morphine at all time
      intervals. However, total opioid consumption was comparable among groups. The
      incidence of side effects was similar in all groups. CONCLUSIONS: There is no
      significant advantage to the routine use of continuous transdermal opioid
      delivery in patients receiving IV PCA after major orthopedic surgery.

PMID- 9172022
TI  - Effects of motion, ambient light, and hypoperfusion on pulse oximeter function.
AB  - STUDY OBJECTIVE: To compare the performance of five pulse oximeters during
      hypoperfusion, probe motion, and exposure to ambient light interference. DESIGN:
      Prospective study. SETTING: Laboratory facility at a university medical center.
      PATIENTS: 8 unanesthetized, ASA physical status I volunteers. INTERVENTIONS: We
      evaluated five common pulse oximeters with respect to three scenarios: (1) an
      operating room light was shone on oximeter probes, (2) a motion generator was
      used to generate 2 Hz and 4 Hz hand motion, and (3) a pneumatic compression
      device overlying the brachial artery was used to simulate hypoperfusion.
      Electrocardiographic (ECG) and arterial blood gas values were considered gold
      standards for heart rate (HR) and oxygen saturation (SpO2) respectively. SpO2
      nondisplay and values greater than 4% from simultaneous arterial SaO2-oximeter
      values were defined as errors. Nondisplay of HR, or HR greater than 5% from ECG
      values, were also considered errors. MEASUREMENTS AND MAIN RESULTS: The Ohmeda
      and Nellcor N200 with finger probe had the highest total failure rates with
      respect to both SpO2 and HR due to ambient light interference (p < 0.05). The
      Nellcor N200 with finger probe and N200 with C lock were the most accurate with
      regard to SpO2 during 2 Hz and 4 Hz motion (p < 0.05). However, all oximeters
      failed dramatically during 4 Hz motion when measuring HR. In the hypoperfusion
      model, the Nellcor N200 with finger probe and the Nellcor C Lock oximeters
      performed significantly better than all others in terms of both HR and SpO2 (P <
      0.05), while the Criticare oximeter failed 100% of the time. CONCLUSION: There
      are significant differences in the accuracy of commercially available pulse
      oximeters during nonideal circumstances, with failure rates varying from
      approximately 5% to 50% depending on the oximeter and source of interference.
      Furthermore, no single oximeter performed the best under all conditions.

PMID- 9172023
TI  - Pulse oximeter performance during desaturation and resaturation: a comparison of
      seven models.
AB  - STUDY OBJECTIVE: To compare pulse oximeter performance during induced hypoxemia.
      DESIGN: Prospective investigation in human volunteers. SETTING: Laboratory
      facility at a university medical center. PATIENTS: 8 unanesthetized, healthy ASA
      physical status I volunteers. INTERVENTIONS: We evaluated the accuracy and
      response times of seven popular pulse oximeters during induced hypoxemia.
      Arterial blood fractional oxygen saturation (SaO2) measurements were performed
      simultaneously and considered a gold standard. MEASUREMENTS AND MAIN RESULTS: All
      oximeters were accurate (+/-2%) while subjects were breathing room air. During
      maximal hypoxemia (induced by breathing a FIO2 = 10% in nitrogen), large
      differences were noted between oxygen saturation as measured by pulse oximetry
      (SpO2) and SaO2 values, with pulse oximeters consistently underreporting SpO2
      when actual SaO2 values were 75% or less. The Ohmeda 3740 (Ohmeda, Boulder, CO)
      using an ear probe was the first to detect desaturation (change in SpO2 > 3%) in
      4 of 8 subjects (p < 0.05), and the Nellcor N200 reflectance oximeter (Nellcor,
      Inc., Pleasanton, CA) was first in 3 of 8 subjects (p < 0.05). During
      resaturation (after administering 100% oxygen), the Novametrix Oxypleth
      (Novametrix, Wallingford, CT) was significantly faster than other oximeters (p <
      0.05) to return to baseline (SpO2 = 98%). CONCLUSION: Most models of oximeters
      tested performed well when hemoglobin oxygen saturation was high, but all were
      inaccurate when SaO2 was approximately 75%. During induced hypoxemia, there were
      significant differences in the response times of oximeters tested, with no model
      demonstrably superior to others in all measures of performance.

PMID- 9172025
TI  - A risk index for pregnancy during anesthesia.
AB  - STUDY OBJECTIVE: To determine the validity of limiting pregnancy testing only to
      females older than 14 years, hypothesizing that (1) if this recommendation were
      valid, we would find no incidence of pregnant patients receiving anesthesia in
      our department under age 15, and (2) by identifying all patients receiving
      anesthesia while pregnant versus those who are not pregnant might allow
      calculation of a relative risk index for pregnancy per age group. DESIGN: A
      retrospective chart review. SETTING: Department of Anesthesiology at Louisiana
      State University Medical Center in Shreveport. MEASUREMENTS AND MAIN RESULTS: The
      relative numbers and ages of 1) all male versus female patients treated, 2)
      females presenting with viable pregnancy receiving anesthetic care, and 3) ages
      of conception in the youngest females were quantified to 4) correlate relative
      rates for pregnancy/anesthetic at each age. Of 16,033 anesthetics administered,
      1,849 pregnant patients ages 13 to 44 years received 1,968 anesthetics (12.5% of
      total). One patient conceived at the age of 12. The rates of pregnant 13 (n = 4)
      and 14 (n = 24) year-olds in our anesthetized population equaled rates found with
      patients in the third and fourth decades of life, respectively. CONCLUSIONS:
      Louisiana State University Medical Center's current departmental guideline to
      preoperatively test all patients aged 12 to 44 years is supported by the desire
      to identify pregnancy prior to anesthesia and the encountered pregnancy
      distribution and incidence. Although radiation is a known danger to fetal
      development, our radiology department tests only females who "fail to confirm in
      writing a nonpregnant state." While females younger than 15 years deserve the
      same consideration as 30- and 40-year-old patients, multiple ethical, pragmatic,
      economic, and theoretical considerations may mitigate the need for mandatory
      testing of all patients.

PMID- 9172024
TI  - Postthyroidectomy analgesia: morphine, buprenorphine, or bupivacaine?
AB  - STUDY OBJECTIVE: To compare three analgesic regimens for pain relief after
      thyroidectomy. DESIGN: Randomized, double-blind, placebo-controlled study.
      SETTING: Inpatient anesthesia in a university department of endocrine surgery.
      PATIENTS: 342 patients scheduled for elective thyroidectomy with nitrous oxide
      oxygen-isoflurane anesthesia in addition to fentanyl. INTERVENTIONS: Group 1
      received preoperative oral controlled release morphine 10 mg, and Group 2
      received postoperative sublingual buprenorphine 0.2 mg. Group 3 received 0.25%
      bupivacaine (10 ml) wound infiltration before skin closure. Eight hours after
      tracheal extubation, patients received a second dose of the same drug in each
      group except in Group 3, where medication was changed to sublingual buprenorphine
      0.2 mg. MEASUREMENTS AND MAIN RESULTS: Patients in Group 2 required fewer
      additional analgesics: 0.54 +/- 0.68 vs. 0.96 +/- 0.84 in Group 1 and 0.79 +/-
      0.78 in Group 3. Patients in Group 2 demonstrated a better pain score and this
      group showed a higher percentage of satisfied patients: 96% vs. 85% in Group 1
      and 91% in Group 3. Group 2 also included more patients requiring no analgesics:
      56% vs. 32% in Group 1 and 42% in Group 3. The side effects in all three groups
      did not differ. CONCLUSION: The administration of sublingual buprenorphine after
      thyroidectomy provides better analgesia than small doses of oral controlled
      release morphine or than 0.25% bupivacaine wound infiltration at the end of
      surgery.

PMID- 9172026
TI  - Comparison of general anesthesia with and without lumbar epidural for total hip
      arthroplasty: effects of epidural block on hip arthroplasty.
AB  - STUDY OBJECTIVES: To determine whether lumbar epidural anesthesia, when combined
      with general anesthesia, decreases perioperative blood loss, the incidence of
      postoperative deep vein thrombosis (DVT), cardiac dysrhythmias, and ischemia in
      patients undergoing total hip arthroplasty (THA). DESIGN: Randomized, controlled
      study. SETTING: A university hospital. PATIENTS: 37 ASA physical status I, II,
      and III patients, undergoing elective THA. INTERVENTION: Patients were divided
      into two statistically comparable groups: Group GA = general anesthesia; Group
      CEGA = general anesthesia plus lumbar epidural anesthesia. All patients had 48
      hour perioperative Holter monitoring, applied on admission, the day prior to
      surgery. In both groups, general anesthesia was induced with thiopental sodium
      and muscle relaxant, and maintained with oxygen, nitrous oxide, isoflurane,
      opioid, and muscle relaxant. Group B received lumbar epidural anesthesia with 10
      ml 0.5% bupivacaine with 1:200,000 epinephrine prior to anesthesia induction.
      Blood loss was measured by suction bottle contents, sponge weights, and
      collection drainage. DVT was assessed with postoperative leg scanning,
      plethysmography, and venogram. MEASUREMENTS AND MAIN RESULTS: Intraoperative
      blood loss was less after combined epidural-general anesthesia (663.8 ml +/-
      299.0 ml) than after general anesthesia alone (1,259.2 ml +/- 366.0 ml). The
      difference was found to be statistically significant (p < 0.00005). No difference
      was found between the two groups in postoperative blood loss, incidence of DVT,
      cardiac dysrhythmias, or ischemia. CONCLUSION: Combined regional-general
      anesthesia decreases intraoperative blood loss in THA, and thereby offers an
      advantage over general anesthesia alone.

PMID- 9172027
TI  - Priming with rocuronium accelerates the onset of neuromuscular blockade.
AB  - STUDY OBJECTIVE: To investigate the effects of priming rocuronium on the time
      course of neuromuscular blockade. DESIGN: Prospective, controlled, randomized
      clinical study. SETTING: University teaching hospital. PATIENTS: 42 ASA physical
      status I and II patients undergoing peripheral surgery with general anesthesia.
      INTERVENTIONS: Following a standardized propofol-fentanyl induction, patients in
      Group 1 (n = 21) received a priming dose of rocuronium 0.06 mg/kg followed two
      minutes later by an intubating dose of rocuronium 0.54 mg/kg. Patients in Group 2
      (n = 21) received a saline placebo injection followed two minutes later by
      rocuronium 0.6 mg/kg. Anesthesia was maintained with isoflurane and nitrous oxide
      60% in oxygen. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was assessed
      at the wrist using mechanomyography with a single-twitch mode of stimulation at a
      frequency of 1 Hz until tracheal intubation and at 0.1 Hz thereafter. The times
      from injection of the intubating dose of rocuronium until 95% suppression of the
      twitch tension (onset time), recovery of twitch tension to 25% of control
      (clinical duration of action), and the time from 25% to 75% spontaneous recovery
      of twitch tension (recovery index) were recorded. The trachea was intubated at
      95% depression of the twitch tension and the intubating conditions were graded
      using a 3-point scale. The onset times with priming rocuronium (34 +/- 6 s) were
      significantly shorter (p < 0.01) than those without priming (59 +/- 14 s). The
      intubation conditions were similar in the two groups; however, the intubating
      times with priming were significantly shorter. The clinical duration of action
      and the recovery index did not differ significantly between the two groups.
      CONCLUSIONS: Priming rocuronium decreased the onset times and thus, the
      intubating times without increasing the clinical duration of action or recovery
      index.

PMID- 9172028
TI  - Is management of anesthesia in achondroplastic dwarfs really a challenge?
AB  - STUDY OBJECTIVE: To review our eight-year anesthetic experience with
      achondroplastic patients. DESIGN: Retrospective study. SETTING: University
      hospital. PATIENTS: 15 achondroplastic patients who underwent 53 surgical
      procedures of orthopedic surgery between 1987 and 1994. INTERVENTIONS: Anesthetic
      technique, drugs, number of incidents, and complications in the intraoperative
      and postoperative period were recorded. MEASUREMENTS AND MAIN RESULTS: Adequate
      premedication before the transfer to the operating room was very useful to reduce
      anxiety and increase cooperation. Inhalation induction was well tolerated and
      allowed easy peripheral venous cannulation. Only one patient presented
      difficulties during intubation (on two occasions). In the other patients, we
      found small difficulties only during ventilation with a face mask, which was
      easily corrected by modifying the position of the patient and/or inserting an
      oropharyngeal airway. No adverse effect was identified for any particular
      anesthetic drug or technique used. CONCLUSIONS: Although the characteristic
      deformities of achondroplastic patients can impede the management of anesthesia,
      in our study we found no special difficulties. Airway complications did not
      occur. Thus, no specific optimal anesthetic regimen can be recommended.

PMID- 9172029
TI  - Cancellation of pediatric outpatient surgery: economic and emotional implications
      for patients and their families.
AB  - STUDY OBJECTIVE: To determine the cause and timing of case cancellation in a
      pediatric outpatient surgical population, and to examine the economic and
      emotional impact of such cancellations on patients and their families. DESIGN:
      Questionnaire survey. SETTING: Outpatient surgery unit of a large university
      children's hospital. PARTICIPANTS: 127 parents of children whose elective
      outpatient surgery had been cancelled. INTERVENTIONS: A total of 200
      questionnaires were mailed to the parents of children who had their outpatient
      surgery cancelled. MEASUREMENTS AND MAIN RESULTS: Of those children whose surgery
      had been cancelled, 34.6% were due to upper respiratory infections (URIs), 30.7%
      for other medical reasons, and the balance for scheduling errors, because the
      child had not fasted, or for difficulties with transportation. The majority of
      surgeries (58.3%) were cancelled prior to their scheduled surgery date. However,
      18.9% were cancelled on the day of surgery prior to leaving for the hospital and
      22.8% were cancelled on arrival at the outpatient surgery clinic. Of those
      patients whose surgeries were not cancelled until they arrived at the hospital,
      38.5% of mothers and 50.0% of fathers missed a day of work and, of these, 53.3%
      and 42.1%, respectively, went unpaid for the work day missed. The mean number of
      miles driven (round trip) to the hospital for a cancelled operation was 158.8
      miles (range 8 to 1,350 miles). Additional testing and new appointments were
      ordered in 25.2% of the cancelled cases. 45% of parents and 16% of children were
      disappointed by the cancellation; 16% of parents were frustrated by the
      cancellation and 3.3% were angry. CONCLUSIONS: This study suggests that last
      minute cancellation of surgery has an important impact on patients and their
      families and suggests a need to review present protocols for screening patients
      prior to surgery.

PMID- 9172030
TI  - Safe anesthetic management of patients undergoing a novel method of treating
      human hepatocellular cancer.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of monitored anesthesia care
      (MAC) in patients who undergo a novel treatment for hepatocellular cancer in
      which procedure-related hemodynamic instability is problematic. DESIGN:
      Nonrandomized open study. SETTING: University cancer center operating room.
      PATIENTS: Nine patients scheduled for hepatic arterial infusion of doxorubicin
      with complete hepatic venous isolation and extracorporeal chemofiltration (no
      more than 3 procedures per patient). INTERVENTIONS: Hepatic venous isolation was
      achieved with a dual-balloon inferior vena cava catheter connected to an
      extracorporeal circuit containing chemofilters. Doxorubicin was infused through
      the hepatic artery and filtered from the venous blood, which was returned to the
      patient through an internal jugular venous catheter. Each patient received a
      bolus of propofol (200 micrograms/kg) and one of alfentanil (2 micrograms/kg)
      followed by simultaneous infusions of propofol and alfentanil for percutaneous
      placement of the catheters and operation of the extracorporeal circuit. Drug
      rates were varied to maintain a sedative-analgesic state of calm, comfort,
      minimal movement, and adequate respiratory function. Prior to circuit initiation,
      patients were preloaded with crystalloid. During circuit operation, hypotension
      was treated with intravenous (IV) phenylephrine and crystalloid. MEASUREMENTS AND
      MAIN RESULTS: End-tidal CO2 (PETCO2), respiratory rate, oxygen saturation (SaO2),
      arterial blood pressure (BP), and heart rate (HR) were monitored. Systolic,
      diastolic, and mean arterial pressure (MAP), and HR were compared before, during,
      and after hepatic venous isolation and chemofiltration. Doses and infusion rates
      of propofol, alfentanil, and phenylephrine were recorded for each treatment.
      Hypotension occurred in 11 of 13 procedures when blood was directed through the
      chemofilters and was successfully treated with phenylephrine (dose range 40 to
      5,733 micrograms) and crystalloid. Blood pressure returned to the baseline value
      on termination of the circuit. Throughout the sedation, patients were easily
      arousable, analgesia was adequate, and PETCO2 level of 38 +/- 4 mmHg and SaO2
      greater than 94% were maintained. Mean doses and infusion rates of MAC drugs
      were, respectively: propofol, 261 +/- 88 mg and 23.7 +/- 3.6 micrograms/kg/min;
      alfentanil, 3,350 +/- 1,468 micrograms and 0.32 +/- 0.14 microgram/kg/min.
      CONCLUSIONS: Patients undergoing this novel cancer treatment are safely and
      effectively managed by MAC achieved with simultaneous infusions of alfentanil and
      propofol. Procedure-associated hypotension is easily treated with IV
      phenylephrine and crystalloid.

PMID- 9172031
TI  - Effects of gas flow management on postintubation end-tidal anesthetic
      concentration and operating room pollution.
AB  - STUDY OBJECTIVE: To study how different anesthetic practices during the
      transition from anesthetic delivery by mask to endotracheal intubation affect end
      tidal postintubation anesthetic concentration and operating room (OR) pollution.
      DESIGN: Prospective study. SETTING: Anesthesia research laboratory. MEASUREMENTS
      AND MAIN RESULTS: We studied four gas flow management practices: practice
      vaporizer off, only the anesthetic vaporizer was turned off; all off, oxygen
      (O2), nitrous oxide (N2O), and the vaporizer were turned off; gas off: O2 and N2O
      were turned off; and all on: neither the gas flows nor the vaporizer were turned
      off. A model of inhalational anesthetic induction was simulated by using an adult
      circle system attached to a reservoir bag ("artificial lung"). By using a fixed
      gas flow, we achieved an end-tidal N2O (ETN2O) concentration of 70% and end-tidal
      halothane (ETHal) concentration of 3%, then stopped mechanical ventilation and
      performed the four practices for a 30-second "intubation" period. During this
      time, the reservoir bag was disconnected from the circuit, and the gas volume
      exiting the circuit (pollution volume) was measured. After this 30-second
      disconnect period, the bag was reconnected to the anesthetic circuit, and the
      original ventilation, gas flows, and vaporizer setting were resumed. The
      anesthetic concentrations were measured at 10, 20, and 30 seconds after
      reconnection. For the vaporizer off practice, ETHal was low and did not return to
      equilibrium within 30 seconds (p < 0.05); ETN2O clinically was unaltered. In the
      all off practice, anesthetic concentrations were below equilibrium at 10, 20, and
      30 seconds (p < 0.05). For the gas off practice, ETHal was slightly below
      equilibrium at all times; ETN2O was below equilibrium at 10, 20, and 30 seconds
      (p < 0.05). In the all on practice, end-tidal anesthetic concentrations were
      unchanged when compared with equilibrium (p > 0.05). Pollution volumes in the
      vaporizer off and all on practices were ten-fold higher than in the all off and
      gas off practices (p < 0.05). CONCLUSION: In a mechanical model of anesthetic
      induction, turning the gas flows off before "intubation" and leaving the
      vaporizer on (the gas off practice) maintained "postintubation" end-tidal drug
      concentrations close to "preintubation" equilibrium and minimized OR pollution.

PMID- 9172032
TI  - Very limited air elimination capability of the level 1 fluid warmer.
AB  - STUDY OBJECTIVE: To determine the volume of air in 1000-ml crystalloid bags
      before and after connection to an infusion set; and to determine the volume of
      air that is not eliminated by the air eliminator in the Level 1 fluid warming
      device (Level 1 Technologies, Inc., Rockland, MA) when air boluses of different
      volumes enter into the fluid warming set. DESIGN: Prospective analysis and
      laboratory investigation. SETTING: Operating room (OR) and research laboratory of
      a university hospital. INTERVENTIONS: Air was aspirated from 200 collapsible,
      1000-ml crystalloid bags: 100 before being connected to an infusion set and 100
      after being connected to a patient in the OR. A roller pump from a
      cardiopulmonary bypass machine was connected to a Level 1 D-300 fluid
      administration set to maintain a continuous flow of normal saline through its air
      eliminator at a flow that approximated gravity or two thirds maximal flow, which
      is the rate achieved when fluid is pressurized to 300 mmHg throughout the system.
      Different volumes of air were administered and the air that passed through the
      air eliminator was measured. MEASUREMENTS AND MAIN RESULTS: Nonspiked bags
      contained 56.2 +/- 4 ml (mean +/- SD) of air (range 43-66 ml), and spiked bags
      contained 61.2 +/- 13 ml of air (range 4-102 ml), a significant difference (p <
      0.0001). The amount of air passing through the air eliminator differed
      significantly at gravity and at two thirds maximal flow with boluses of 5, 10,
      20, and 30 ml of air (p < 0.0001), but not with the 60 ml bolus of air. The
      amount of air passing through the eliminator also differed significantly (p <
      0.0001) between boluses of different sizes at each flow rate. At the higher flow
      rate, even small boluses of air were not reliably eliminated; up to 56% of a 5 ml
      air bolus passed through the eliminator. CONCLUSION: Air must be rigorously
      eliminated from all fluid containers because of the limited air elimination
      capability of the Level 1 air eliminator.

PMID- 9172034
TI  - Laryngotracheal anesthesia device as jet ventilation cannula for removal of
      fragmented intratracheal T-tube.
AB  - For tracheotomy procedures with general anesthesia, adequate surgical exposure,
      oxygenation, and ventilation of the lungs can be obtained by different
      techniques. We present a method of jet ventilation with use of a modified
      laryngotracheal anesthesia (LTA) device as a jet ventilation cannula during
      retrieval of a tracheal T-tube that broke within the trachea during removal. To
      our knowledge, this report is the first to document friability and subsequent
      difficult removal of a tracheal T-tube after intubation longer than recommended
      by the manufacturer. It is also the first report of a new technique using a
      simple LTA device modification to provide oxygen insufflation or jet ventilation
      in this or similar situations.

PMID- 9172033
TI  - A case of acute pulmonary edema and bulbar paralysis after local epinephrine
      infiltration.
AB  - An unusual case in which pulmonary edema and intracranial hemorrhage occurred
      during adenotonsillectomy is presented. The possible causes of this intracranial
      hemorrhage are discussed, especially in relationship to local epinephrine
      infiltration.

PMID- 9172035
TI  - Management of a postpartum coagulopathy using thrombelastography.
AB  - Thrombelastography (TEG), which evaluates the elastic properties of whole blood
      and provides a global assessment of hemostatic function, is useful in managing
      peripartum coagulopathy. A case of severe bleeding after vaginal delivery, in
      which TEG was used successfully to manage hemostatic defects, is presented.

PMID- 9172036
TI  - Successful early intervention in air embolism during hysteroscopy.
AB  - Hysteroscopy is used as a diagnostic tool for intrauterine pathology. Gas
      embolism with air or carbon dioxide is a rare but sometimes fatal complication of
      laparoscopy or hysteroscopy. We present a patient who developed pulmonary air
      embolism during hysteroscopy that caused a noncardiogenic pulmonary edema in the
      recovery room. This case report emphasizes that early intervention can prevent
      life-threatening events associated with pulmonary embolism during hysteroscopy.
      Pathophysiology of pulmonary gas embolism, as well as that of noncardiogenic
      pulmonary edema, is discussed. A protocol for the prevention, early detection,
      and management of this emergency is provided.

PMID- 9172037
TI  - Venous air embolism: a review.
AB  - Venous air embolism (VAE) can be a lethal complication of surgical procedures,
      during which (1) venous pressure at the site of surgery is subatmospheric or (2)
      gas is forced under pressure into a body cavity. Though classically associated
      with neurosurgery, VAE is also a potential complication of laparoscopic, pelvic,
      and orthopedic procedures. It is, therefore, essential for the practicing
      anesthesiologist to recognize and treat venous air entrainment. An in-depth
      review of the pathophysiology, clinical presentation, detection, prevention, and
      treatment of VAE is presented.

PMID- 9172038
TI  - Postdural puncture headache and ACTH.

PMID- 9172039
TI  - Latex exposure from anesthesia equipment.

PMID- 9172040
TI  - Infection control and the Internet.
AB  - The Internet can be enormously valuable for infection control workers. It
      provides access to policy documents and discussion groups debating everyday
      problems, and is a comprehensive source of information on infection-related
      topics. Here we discuss some of the more useful Internet connections.

PMID- 9172041
TI  - Protecting the patient and the environment--new aspects and challenges in
      hospital infection control.
AB  - Environmental pollution has become a major concern for the future of life on our
      planet; medical care, especially in hospitals, contributes significantly to this
      pollution. The increasing usage of highly-developed medical devices, drugs and
      disposable products are a drain on natural resources as well as financial ones.
      In this situation, it is a major task for hospital epidemiologists to maintain
      high standards of hygiene while reducing environmental pollution, reducing
      consumption of limited natural resources, and minimizing costs. The reduction of
      hospital waste, the control of polluting and toxic emissions, the avoidance of
      unnecessary disinfection procedures and disposables, the implementation of energy
      and water saving technologies are practicable measures in hospital ecology. To
      realize a sustainable development within hospitals, it is necessary that the need
      to maintain a balance between effective infection control and a good ecological
      environment is recognized and supported by health-care workers and the hospital
      management.

PMID- 9172042
TI  - Environmental auditing in hospitals: approach and implementation in an university
      hospital.
AB  - Medical audit in infection control today is accepted as an important element in
      the quality assurance of health care. In contrast, environmental auditing, which
      was approved in 1993 by the Council of the European Communities for industry
      ("Eco-Management and Audit Scheme-EMAS), has not so far been used as a tool to
      control and reduce environmental pollution caused by medical care in hospitals.
      The aim of this study was to investigate, whether environmental auditing in
      hospitals is useful. This process should also be cost effective. In this paper,
      methodological and organizational issues are described. Initially an
      environmental review of activities at the University Hospital, Freiburg and an
      eco-analysis of the input and output were performed. The first results of the
      study and a critical discussion will be presented in another paper.

PMID- 9172043
TI  - Epidemiological typing of extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae isolates responsible for five outbreaks in a university hospital.
AB  - Thirty-seven isolates of extended-spectrum beta-lactamase-producing (ESBL)
      Klebsiella pneumoniae implicated in five nosocomial outbreaks (I-V) on three
      distinct wards of our hospital were compared using capsular typing, biotyping,
      antibiotyping, enzyme electrophoresis typing and DNA macrorestriction analysis
      with Xba I resolved by pulsed-field gel electrophoresis. The isolates from each
      outbreak had common phenotypic and genotypic characteristics indicating that they
      were related epidemiologically. Isolates from outbreaks I (four patients) and V
      (13 patients), although they occurred in two different wards (neurology and
      surgery) and three years apart, produced the same ESBL with a pI of 7.8 (SHV-4)
      and were of serotype K25. The Xba I patterns were closely related. The isolates
      of outbreaks II (seven patients), III (four patients) and IV (seven patients),
      which occurred in a single surgical intensive care unit, produced an ESBL with a
      pI of 6.3 (TEM-3). Isolates from outbreaks III and IV, which occurred six months
      apart, were of serotype K68 and had similar Xba I patterns suggesting that the
      two outbreaks were due to a single strain which persisted endemically in the
      ward. The isolates from outbreak II were of serotype K62, and had distinct
      characteristics from the two later outbreaks. The Xba I patterns of the isolates
      from outbreaks "I and V', II and "III and IV' had Dice similarity coefficients
      under 40% showing that the three groups were genetically distant. DNA
      macrorestriction analysis was a useful complement to phenotypic methods for
      identifying K. pneumoniae strains responsible for outbreaks harbouring a common
      ESBL.

PMID- 9172044
TI  - Investigation of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in
      an Irish hospital: triplex PCR and DNA amplification fingerprinting.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is becoming a problematic
      nosocomial pathogen. A continuing increase in numbers of isolates is reported
      from Irish hospitals each year. Preventing cross-infection and the further spread
      of endemic strains requires effective control measures. This necessitates the
      development of sensitive methods for both detection and genetic identification of
      MRSA isolates. In this study, 48 MRSA strains isolated in the Cork University
      Hospital were analysed between January and July 1995 using a one-tube triplex
      polymerase chain reaction (PCR), wherein three genes, the methicillin-resistance
      gene (mecA), femA and the extracellular thermonuclease gene, nuc, were
      simultaneously amplified. Methicillin-sensitive S. aureus (MSSA) and coagulase
      negative staphylococci (CNS) were also tested and the assay was found to be MRSA
      specific. The genetic relationship among this collection of MRSA isolates was
      also investigated. A single primer, RW3A, derived from a well-characterized,
      repetitive sequence found in Mycoplasma pneumoniae produced discriminating DNA
      fragment arrays with all the study organisms. The patterns were reproducible,
      even after several passages of the isolates. Quantitative analysis of the
      patterns divided the collection into two main groups, DAF group I representing
      48% of the collection and DAF group II a further 19%. The remaining strains
      showed unrelated patterns. To fully outline the distribution of MRSA in this area
      a larger study will be necessary. This paper outlines the applicability of both
      the identification and fingerprinting techniques to local strains.

PMID- 9172045
TI  - An evaluation of five protocols for surgical handwashing in relation to skin
      condition and microbial counts.
AB  - Five protocols for surgical handwashing (scrubbing) were evaluated for their
      efficiency of removal of micro-organisms and their drying effect on the skin. The
      scrubbing protocols tested were: (1) an initial scrub of 5 min and consecutive
      scrubs of 3.5 min with chlorhexidine gluconate 4% (CHG-5); (2) an initial scrub
      of 3 min and consecutive scrubs of 2.5 min with chlorhexidine gluconate 4% (CHG
      3); (3) an initial scrub of 3 min and consecutive scrubs of 2.5 min with povidone
      iodine 5% and triclosan 1% (PI-3); (4) an initial scrub of 2 min with
      chlorhexidine gluconate 4% followed by a 30 s application of isopropanol 70% and
      chlorhexidine gluconate 0.5%, and a 30 s application of isopropanol 70% and
      chlorhexidine gluconate 0.5% for consecutive scrubs (IPA); and (5) an initial
      scrub of 2 min with chlorhexidine gluconate 4% followed by a 30 s application of
      ethanol 70% and chlorhexidine gluconate 0.5%, and a 30 s application of ethanol
      70% and chlorhexidine gluconate 0.5% for consecutive scrubs (EA). A convenience
      sample of 23 operating theatre nurses completed each scrub protocol for one week
      in a randomized order. A week of normal work activities intervened between each
      protocol. Subjects were assessed before commencing and after completing the week
      of each protocol to determine changes in the microbial counts and skin condition
      of the hands. Specimens for microbial analysis were collected before, immediately
      after and 2 h after an initial scrub, and 2 h after a consecutive scrub. The CHG
      5, CHG-3 and PI-3 protocols, which used detergent-based antiseptics only, were
      compared with protocols incorporating an alcohol-based antiseptic (IPA and EA).
      The protocols incorporating alcohol-based antiseptics and the CHG-5 protocol were
      generally associated with the lowest post-scrub numbers of colony forming units
      (cfu). No difference between the CHG-5 protocol and the alcohol-based antiseptics
      was found at the beginning of the test week, but after exclusive use of the
      respective protocols for a week, the alcohol-based antiseptics were associated
      with significantly lower cfu numbers in two out of the three post-scrub samples
      (P = 0.003, P = 0.035). Although virtually no statistically significant
      differences in skin condition were found, many subjects reported the alcohol
      based antiseptic protocols to be less drying on the skin. The findings of this
      study support the proposition that a scrub protocol using alcohol-based
      antiseptics is as effective and no more damaging to skin than more time
      consuming, conventional methods using detergent-based antiseptics.

PMID- 9172046
TI  - Central venous catheter-related septicaemia in paediatric cancer patients.
AB  - A prospective study of septicaemia, with special reference to central venous
      catheter (CVC)-related septicaemia, was performed over a nine-month period in
      paediatric cancer patients undergoing anti-neoplastic therapy. A total of 142
      patients with 153 CVCs were included in the study. Seventy-two episodes of
      septicaemia were detected in 66 patients; overall, 46% of patients developed one
      or more episodes of septicaemia. Thirty-nine (54%) of these episodes occurring in
      34 patients were CVC-related. Twenty-one (29%) of the episodes occurring in
      twenty patients were probably unrelated to CVCs and 12 (17%) episodes in 12
      patients were of uncertain source. A total of 22932 CVC days were studied. The
      rate of CVC-related septicaemia was 1.7 episodes/1000 catheter days. Gram
      positive organisms were commonest, causing 34 (87%) episodes of CVC-related
      septicaemia. Twenty-five (71%) of 35 evaluable episodes were successfully treated
      with antibiotics without CVC removal. Two patients died, CVC related sepsis
      probably contributing to death, and one patient suffered prolonged morbidity
      associated with CVC sepsis. Gram-negative organisms were the commonest cause of
      CVC-unrelated septicaemia, being implicated in 13 (62%) episodes.

PMID- 9172047
TI  - Inter-hospital spread of vancomycin-resistant Enterococcus faecium.

PMID- 9172048
TI  - Long-term methicillin-resistant Staphylococcus aureus (MRSA) carriage and tagging
      of patient records.

PMID- 9172049
TI  - Species differences in PAF receptor binding in the lungs between hamster and
      guinea pig.
AB  - Platelet-activating factor (PAF) receptor in normal Golden Syrian hamster lung
      was characterized using radioligand binding studies and compared with guinea pig
      lung PAF receptor. [3H]WEB2086, a potent and specific PAF antagonist, was used as
      a radioligand for equilibrium binding, kinetic studies, competitive binding in
      receptor preparation (0-110000 g fraction of lung homogenate) from hamster and
      guinea pig lungs. Binding of [3H]WEB 2086 to the receptor preparation was
      saturable, reversible and specific in both hamster and guinea pig lungs.
      Scatchard plot analysis of equilibrium binding data indicates a single binding
      site in hamster lung with the equilibrium dissociation constant (KD) of 66.1 +/-
      36.7 nM (n = 4) and maximal binding (Bmax) of 135.4 +/- 63.1 fmol/mg, but two
      binding sites in guinea pig lung with a high affinity site (KD = 1.7 +/- 0.6 nM;
      Bmax = 48.6 +/- 2.6 fmol/mg) and a low affinity site (KD = 83.8 +/- 32 nM; Bmax =
      480.8 +/- 158 fmol/mg). The heterogeneity of [3H]WEB2086 binding to guinea pig
      lung but not to hamster lung was also confirmed by dissociation kinetic studies,
      in which biphasic dissociation kinetic was shown in guinea pig and monophasic
      kinetic in hamster lung. Although the specific [3H]WEB 2086 binding to lungs of
      both species was displaced by PAF-C18 and antagonists L659989 and CL184005 in a
      dose-dependent manner and not by lyso-PAF (a biologically inactive form of PAF),
      the potencies of the competitive inhibition were significantly different between
      the two species. The relative potencies ranked WEB2086 approximately L659989 >
      PAF > CL184005 in hamster lung, whereas in guinea pig lung the potencies ranked
      PAF > WEB2086 approximately L659989 approximately CL184005. The present study
      demonstrates for the first time the existence of PAF receptor in the hamster lung
      and its binding characteristics different from guinea pig lung suggest the
      possible existence of different PAF receptor subtypes in hamster lung.

PMID- 9172050
TI  - A pharmacophore for high affinity PAF antagonists. II. Hydrophobicity study using
      the molecular lipophilicity potential.
AB  - Platelet-activating factor (PAF) is a powerful phospholipid-derived autacoid
      involved in many physiopathological mechanisms. Many PAF antagonists have been
      synthesized and evaluated as therapeutic candidates. In a previous report, we
      have described an electronic pharmacophore of PAF antagonists using the molecular
      electrostatic potential. In the present study, a molecular lipophilicity
      potential is used to compare the hydrophobic properties of 49 "heterocyclic sp2
      nitrogen' highly potent PAF antagonists, belonging to six structurally different
      series (nine hetrazepines, five pyrrolo[1,2-c]thiazoles, 14 carboxamides, nine
      dihydropyridines, nine pyridinyl-thiazolidines and three imidazo[4,5
      c]pyridines). Their common features consist of three hydrophilic (HYD2, HY14(3)B
      and HYD3) and two lipophilic zones (LIP3 and LIP4), defining the lipophilic
      pharmacophore of the antagonists. This pharmacophore is also characterized by
      several zone-to-zone distances: HYD3-HYD2 = 1.3 +/- 1.0 A, HY3B-HYD2 = 7.8 +/-
      1.1, HYD3-HY3B = 5.1 +/- 1.1 A, LIP4-LIP3 = 5.4 +/- 1.1 A, LIP3-HYD2 = 11.3 +/-
      1.6 A, LIP3-HY3B = 5.9 +/- 1.0 A, LIP3-HYD3 = 4.3 +/- 0.9 A, LIP4-HYD2 = 14.7 +/-
      1.6 A, LIP4-HY3B = 8.1 +/- 1.2 A and LIP4-HYD3 = 3.9 +/- 1.1 A. These results
      represent a new step in the determination of a global pharmacophore for PAF
      antagonists.

PMID- 9172051
TI  - Endothelin-1-induced placental and fetal growth restriction in the rat.
AB  - The objective of this study was to evaluate the effect of increased circulating
      endothelin on fetal and placental growth in the rat. Indwelling arterial and
      venous catheters were placed on day 14 of a 22-day gestation in timed-pregnant
      Sprague-Dawley rats. Saline, 0.2 nmol/kg/h endothelin, or 0.5 nmol/kg/h
      endothelin was continuously infused from day 15 through 21 in randomly assigned
      animals (n = 12 in each group). Maternal arterial blood pressure and serum
      endothelin levels were evaluated on days 15, 18, and 21 of gestation. On day 21,
      pregnancy outcome data including fetal and placental weights, litter size, and
      the occurrence of stillbirths were ascertained, and fetal blood was obtained for
      serum endothelin levels. All data were compared among the three groups, and
      statistical significance was determined by analysis of variance. Endothelin
      infusion resulted in a dose-dependent decrease in fetal and placental weights
      when compared to saline-treated pregnancies. A significant increase in maternal
      arterial blood pressure was noted only in the 0.5 nmol/kg/h endothelin group.
      Fetal and placental growth restriction occurred in the absence of maternal
      hypertension in the 0.2 nmol/kg/h group. These results demonstrate that
      endothelin infusion causes restriction of fetal and placental growth, even in the
      absence of maternal hypertension.

PMID- 9172052
TI  - Increased fetal colonic muscle contractility following glucocorticoid and
      thyroxine therapy: implications for meconium passage.
AB  - The incidence of meconium-stained amniotic fluid increases with advanced
      gestational age and fetal stress, and meconium passage is likely dependent on
      fetal colonic muscle function. Antenatal hormone exposure improves fetal
      pulmonary and cardiovascular function. We hypothesized that in utero exposure to
      steroid or thyroid hormones effect an increase in fetal distal colonic muscle
      contractility. In a randomized controlled study 126-day (term 145 days) ovine
      fetuses were treated with a single ultrasound-guided intramuscular injection of
      0.5 mg/kg betamethasone (n = 5), betamethasone plus 60 micrograms/kg thyroxine (n
      = 5), or saline (n = 7). After 48 h, fetuses (128 days) were delivered, distal
      colon segments were removed, and peak tension responses to bethanechol (10(-8) to
      10(-3) M) characterized in vitro. Peak muscle tensions were significantly greater
      in fetuses exposed to combined betamethasone and thyroxine therapy (989 +/- 190
      g/cm2) than in saline-treated animals (509 +/- 91 g/cm2). There was difference in
      the maximum tension response between betamethasone alone (559 +/- 75 g/cm2) and
      the saline animals. The bethanechol ED50 values (2.1 +/- 0.5 x 10(-5) M) were not
      different among the three groups. Antenatal fetal betamethasone and thyroid
      hormone treatment increases fetal colonic muscle contractility. We speculate that
      endogenous or exogenous fetal maturational agents may facilitate the passage of
      meconium.

PMID- 9172053
TI  - Effects of maternal exercise on fetal activity in late gestation.
AB  - In order to test the effects of maternal exercise in late gestation on fetal
      biophysical activities as measured by fetal breathing, shoulder movement, and
      kick response, these parameters were monitored by ultrasound in ten healthy
      pregnant women at 35 weeks of gestation before and after 20 minutes of aerobic
      dance and before and after 20 minutes of rest. A randomized crossover design
      between exercise (sequence A) and rest (sequence B) that used each pregnant woman
      as her own control was used in this study. Cumulative means for each fetal
      activity were compared. Results indicated a significant decrease in fetal
      breathing after maternal exercise and no significant change in shoulder movements
      or kick response.

PMID- 9172054
TI  - Plasma alkaline phosphatase and pregnancy outcome.
AB  - The objective was to determine the relationship between plasma alkaline
      phosphatase (AP) activity and birthweight (BWT) and preterm delivery (PTD). Five
      hundred eighty African-American women had plasma AP activities measured at
      various gestational ages (GA) with the results compared to a number of pregnancy
      outcomes. Plasma AP activity rose linearly during pregnancy from a mean of 39 U/L
      at 19 weeks to 130 U/L at delivery. In individual women, AP activities were
      consistently high or low as confirmed by correlation coefficients in adjacent
      time periods ranging from 0.63 to 0.87. AP at 19 weeks was not significantly
      associated with any outcome measure. However, at 26 weeks, AP in the highest
      quartile was associated with a 15.0% incidence of PTD < 37 weeks compared to 6.8%
      in the lower three quartiles (P = .004). For PTD < or = 32 weeks, the difference
      of PTD was 6.8 vs. 1.6% (P < .003). When women in the highest quartile of
      increase in AP from 19 to 26 weeks were compared to those in the lower quartiles,
      the rate of PTD < 37 weeks was 15.2 vs. 6.4% (P = .002), and the rate of PTD < or
      = 32 weeks was 6.1 vs. 1.7%, (P = .01). The mean BWT for the highest vs. the
      lower three quartiles in rate of increase was 3,058 vs. 3,288 g (P = .0005) and
      the mean GA was 38.1 vs. 39.2 weeks (P = .0001). Regression analyses adjusting
      for multiple confounders confirmed the association between high AP at 26 weeks
      and PTD < 37 weeks [OR (95% C.I.), 2.4 (1.2-4.8)] and PTD < or = 32 weeks [OR
      (95% C.I.), 3.7 (1.2-11.7)]. Similar results were found among women with a large
      increase in AP between 19 and 26 weeks. From these results we conclude that high
      or increasing AP activity at 26 weeks, but not 19 weeks, was significantly
      associated with subsequent PTD and a lower BWT.

PMID- 9172055
TI  - Method of delivery of the nonvertex second twin: a community hospital experience.
AB  - The purpose of this study is to examine the incidence of cesarean section and
      fetal distress complicating the delivery of the second twin in vertex-nonvertex
      twin gestations in which the second twin underwent either breech extraction or
      external version. The intrapartum courses of 510 twin gestations delivered at a
      community hospital over a 10-year period were retrospectively analyzed. All
      vertex-nonvertex twin gestations were identified in which the second twin
      underwent attempted breech extraction or external version. Exclusion criteria
      included birthweight < or = 1,500 g, fetal anomaly, intrauterine demise, and
      monoamniotic twins. Of the 76 twin sets that met inclusion criteria, 33 underwent
      external version and 43 underwent primary breech extraction. The two groups had
      similar demographic characteristics. External version compared to breech
      extraction was associated with a significantly greater incidence of cesarean
      section (8/33 vs. 1/43, P = .008) and fetal distress (8/33 vs. 1/43, P = .008).
      There was no difference between groups in neonatal outcome for the second twin as
      measured by length of stay, 5-minute Apgar < 7, intensive care unit admissions,
      hyaline membrane disease, intraventricular hemorrhage, and traumatic birth
      injury. In conclusion, the increased incidence of cesarean section and fetal
      distress in patients undergoing attempted external version suggests that breech
      extraction may be the preferable route of delivery for the nonvertex second twin
      weighing more than 1,500 g.

PMID- 9172056
TI  - Candida chorioamnionitis: a report of two cases.
AB  - Intra-amniotic infection (IAI) across intact membranes by Candida albicans is a
      rare occurrence. We report two cases of preterm labor and Candida
      chorioamnionitis that were diagnosed by intrapartum amniocentesis. The diverse
      maternal and neonatal outcomes observed indicate that Candida IAI is associated
      with significant, unpredictable maternal and neonatal morbidity.

PMID- 9172058
TI  - Preterm premature rupture of membranes: comparison between twin and singleton
      gestations.
AB  - The purpose of this study was to evaluate the clinical characteristics and
      pregnancy outcomes of twin and singleton pregnancies complicated by preterm
      premature rupture of membranes (PROM) and to compare the groups to evaluate for
      differences in these areas. In this retrospective study, patients with a
      gestational age of < 36 weeks admitted between 1993 and 1996 with PROM were
      evaluated for their clinical characteristics and pregnancy outcomes. Twin and
      singleton pregnancies were compared and the results were evaluated for
      significant differences. Patients with lethal fetal anomalies, clinical
      chorioamnionitis at presentation, or fetal distress at presentation were excluded
      from analysis. Liberal use of tocolysis was provided to both groups of patients,
      as were serial doses of betamethasone and vitamin K. Twenty-eight sets of twins
      and 119 singleton pregnancies were included in the analysis. Differences were
      noted with respect to twin and singleton pregnancies for both latency period
      (4.26 days vs 8.6 days, P < 0.001) and birthweight (1,464 vs 1,698 g, P < 0.03).
      The birthweight for twins was an average of the pair. No differences were noted
      with respect to gestational age at time of rupture, maternal age, gravidity,
      parity, race, tocolytic use, steroid use, prophylactic antibiotics, or sexually
      transmitted diseases. The incidence of chorioamnionitis showed a trend for a
      higher occurrence in singleton pregnancies. The latency period for twin
      pregnancies complicated by preterm PROM is shorter than for singleton
      pregnancies. The incidence of chorioamnionitis may be higher in singleton
      pregnancies, but this may be related to their longer latency period. A knowledge
      of these differences may be of benefit when counseling these patients.

PMID- 9172057
TI  - Very-low-birthweight breech infants: short-term outcome by method of delivery.
AB  - The purpose of this study was to determine the incidence of mortality and
      morbidity of the very-low-birthweight infant (< 1,500 g) in breech presentation
      based on mode of delivery and birthweight. A retrospective chart review of 1,009
      infants who were in breech presentation at the time of delivery between January
      1, 1990 and December 31, 1995 at the First Department of Obstetrics and
      Gynecology of Semmelweis Medical School in Budapest, Hungary. Data collected
      included birthweight, mode of delivery, pregnancy complications and neonatal
      mortality and morbidity. Comparison of groups was made based on mode of delivery,
      and data were analyzed using Fisher's exact test and chi-square analysis. For
      those infants weighing less than 1,500 g at birth, vaginal delivery was
      associated with higher mortality than for those delivered abdominally (73.8% vs.
      37.7%, P < 0.001). There was no significant difference in survival for those
      infants weighing 1,500 g or more. Regarding morbidity, in those infants weighing
      less than 1,500 g, vaginal delivery was associated with a higher incidence of 1
      min Apgar below 4 (21.7% vs. 5.2%, P < 0.001), a higher incidence of 5-min Apgar
      scores below 4 (11.6% vs. 1.2%, P < 0.001), a higher incidence of grade III or
      grade IV IVH (18.8% vs. 3.5%, P < 0.001) and a higher incidence of necrotizing
      enterocolitis (5.8% vs. 0.6%, P < 0.05). There is an increased incidence of
      mortality and morbidity for the VLBW breech infant delivered vaginally. Cesarean
      delivery may improve outcome for these infants.

PMID- 9172059
TI  - Prenatal characteristics of congenital nephrosis: results of a survey.
AB  - The purpose of this study was to evaluate the prenatal characteristics of
      congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated
      maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound
      examinations and normal fetal karyotypes were included. A retrospective cohort
      study was conducted using questionnaires sent to all board certified clinical
      geneticists. Perinatal outcome, including histologic verification of CNF, was
      obtained. Forty index cases met the above criteria. Ten cases ultimately did not
      have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64
      MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the
      affected cohort of index pregnancies, the initial median MSAFP level was 14.49
      MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9).
      MSAFP and AFAFP levels may be lower than previously recognized in patients
      carrying fetuses with CNF. There is significant overlap between the affected and
      unaffected patients.

PMID- 9172060
TI  - Early fetal growth delay: is it really predictive of congenital anomalies in
      infants of diabetic women?
AB  - It has been reported that the congenital anomalies frequently observed in
      offspring of diabetic women may be predicted by first-trimester ultrasound
      findings that reveal diminution in growth of the embryo/fetus. The aim of the
      current study was to examine the relationship between early growth delay and
      congenital anomalies in pregnancies complicated by diabetes. We conducted a
      retrospective study of 38 patients with insulin-requiring pregestational diabetes
      mellitus and 81 control pregnancies who had first-trimester ultrasound
      examinations. A cross-sectional survey of all patients revealed a congenital
      anomaly rate of 18.4% among the diabetic pregnancies compared to 4.9% among
      controls (P < 0.02). Early fetal growth delay was defined as a difference of six
      or more days between the menstrual gestational age and the sonographic
      gestational age (menstrual age minus ultrasound age). Early growth delay was
      exhibited in fifteen control pregnancies (18.5%) and eleven insulin-requiring
      pregestational diabetic pregnancies (28.9%) (P = 0.02). However the incidence of
      congenital anomalies in these two groups was significantly different, but there
      was no difference between groups with and without growth delay. The longitudinal
      growth of two anomalous fetuses of the diabetic group and three anomalous fetuses
      from the control group was studied. Both groups of fetuses remained within the
      normal growth range for their respective groups. This study described herein
      fails to confirm the association of early fetal growth delay with the occurrence
      of congenital malformations in insulin-requiring pregestational diabetic
      pregnancies.

PMID- 9172061
TI  - Relationship of insulin resistance and hyperinsulinemia to blood pressure during
      pregnancy.
AB  - The purpose of our study was to examine the relationship between insulin
      resistance and blood pressure during pregnancy and to determine to what extent
      insulin resistance is related to the subsequent development of pregnancy-induced
      hypertension. The study population consisted of 292 women who had serum insulin,
      glucose and insulin-glucose ratios determined at 26-28 weeks gestation in a
      fasting state and 1 hr after a 50-g oral glucose challenge. These were compared
      with blood pressures at 26-28 weeks gestation and in the late third trimester. A
      statistically significant correlation exists overall between (1) blood pressure
      at 26-28 weeks gestation and both fasting insulin and insulin-glucose ratios, as
      well as (2) systolic blood pressure at term and fasting insulin levels. However,
      when controlled for confounding variables including body mass index, race and
      age, no statistically significant relationship remained. The metabolic variables
      in patients with pregnancy-induced hypertension were not statistically different
      from the normotensive patients. In conclusion, this study demonstrates that
      insulin resistance and hyperinsulinemia are not major determinants of blood
      pressure during pregnancy.

PMID- 9172062
TI  - Meconium does not guarantee fetal lung maturity.
AB  - OBJECTIVE: In utero passage of meconium may represent a response to hypoxic
      stress or a normal maturational event. When found during the third trimester, one
      may be tempted to use its presence as prima facie evidence of fetal lung
      maturity. The purpose of our study was to determine the frequency of meconium
      stained fluid in the third trimester and the incidence of biochemical and
      physiologic lung immaturity in these fetuses. METHODS: Amniotic fluid specimens
      obtained at our institution from 1991 through 1993 (n = 2,377) were analyzed for
      maturity and visually inspected for meconium. Perinatal outcome was obtained for
      intramural deliveries occurring within 3 days of amniotic fluid collection (n =
      905). Gestational age was defined as the best obstetric estimate based on
      menstrual dates, clinical examination, and ultrasound results. RESULTS: Meconium
      staining was present in 2.7% (n = 64) of specimens. Although meconium-stained
      specimens were more likely to have mature lecithin-sphingomyelin (L:S) ratios (OR
      2.1, 95% confidence interval [CI] = 1.2-3.6) and phosphatidylglycerol (PG)
      concentrations (OR 3.8, CI 2.2-6.7), 17.2% were immature for both L:S and PG (n =
      11, CI = 9.9-28.2%). When analysis was limited to fetuses delivering intramurally
      within 3 days of amniotic fluid collection, respiratory distress syndrome
      occurred in 3.0% (CI = 0.5-15%) with meconium-stained fluid. CONCLUSIONS: The
      presence of meconium in amniotic fluid does not guarantee lung maturity. The same
      consideration of the risks of prematurity must be given to the fetus with
      meconium-stained fluid as given to the fetus with clear fluid.

PMID- 9172063
TI  - Maternal perception of preterm labor: is it reliable?
AB  - The objective of this study was to determine the reliability of maternal
      perception of uterine contractions and the influence of gestational age and
      maternal training on the perception level. Three hundred fifty patients at high
      risk for preterm delivery were followed from 20 to 35 weeks of gestation. The
      average maternal perception (79%) of contractions did not significantly vary as a
      function of gestational age. Four groups of women were identified according to
      the perception index (PI) defined as the ratio of contractions felt by the mother
      and the contractions documented by tocodynamometer. Within each group, the PI did
      not significantly vary during consecutive monitoring sessions, as the women
      become more familiar with self detection of uterine contractions (R < .65, P >
      .95). Twenty-one percent (+/-5%) of all preterm uterine contractions were not
      perceived by the pregnant women from 21 to 35 weeks. Thirty-two patients (9.1%)
      fail to perceive most or all uterine contractions while 189 (54%) detect most or
      all at any time during the study period.

PMID- 9172064
TI  - Relationship between plasma glucose levels in glucose-intolerant women and
      newborn macrosomia.
AB  - The purpose of this study was to examine the relationship between newborn
      macrosomia and plasma glucose profile in both a "glucose challenge test (GCT)
      positive oral glucose tolerance test (OGTT)-negative" group (n = 113) and a
      gestational diabetes mellitus (GDM) group (n = 50). We examined 1) plasma glucose
      concentrations following a positive screen 50-g GCT (n = 163), 2) glucose
      concentrations following a 100-g OGTT (n = 163), and 3) the average fasting (AF)
      and 2-hour postprandial (APP) plasma glucose concentrations in the treated GDM
      group (n = 46). It was a case-control study with macrosomia vs. non-macrosomia in
      the ratio of 1:4. Macrosomia was analyzed by both birthweight > 4,000 g and
      gender-specific birthweight > 90th percentile for gestational age criteria. The
      GCT and the OGTT were performed between 26 and 30 weeks of pregnancy. The results
      demonstrated no significant impact of plasma glucose values from GCT, OGTT, AF,
      or APP on macrosomia in both "GCT-positive OGTT-negative" and GDM (treated)
      groups. Further, the screening and diagnostic plasma glucose concentrations were
      not related to macrosomia in both "GCT-positive OGTT-negative" and GDM groups. We
      found a difference of 0.6 mmol/liter in the maternal AF and APP glucose
      concentrations between mothers of macrosomic versus non-macrosomic newborns in
      the treated (diet or diet+insulin) GDM group. The clinical relevance of this
      difference remains to be explored. Our study provides a different methodological
      and analytic perspective in examining macrosomia versus non-macrosomia in the
      "GCT-positive OGTT-negative" and the GDM groups using univariate and multivariate
      analyses.

PMID- 9172065
TI  - The search for the elusive electronic medical record system--medical liability,
      the missing factor.
AB  - Over the past few years, the traditional paper-based medical record system has
      come under close scrutiny by every participant in the healthcare industry. Some
      groups, especially federal agencies such as Medicare and Medicaid, HMOs, and
      other third party payors, have begun to demand changes in medical record
      documentation, and have become very assertive as to what goals and objectives
      will be met. In contrast, the medical liability insurance industry has remained
      almost invisible during this period of transition. At a recent electronic medical
      records (EMR) conference participants attending a software development workshop
      were asked if they had their systems reviewed from a medicolegal standpoint by a
      malpractice insurance carrier. In response to this inquiry, not one software
      vendor raised their hand to indicate this had been accomplished, or was even
      contemplated. In the author's opinion, the key missing factor in the current
      quest for a paperless medical office system rests in the domain of those who
      represent the medical liability industry. All of these gate-keepers of medical
      loss and risk prevention will eventually be called upon, either by choice or
      necessity, to validate every working EMR system that is used in medical practices
      in the future. This article will explore the best information published from this
      currently silent sector of the industry, and proposes an active involvement by
      the medical liability industry in the current EMR design and development
      processes taking place. In addition, there are 10 minimum EMR design criteria
      contained in this article that are recommended for implementation based upon 16
      years of medical malpractice experience and loss prevention input.

PMID- 9172066
TI  - Data quality of administratively collected hospital discharge data for liver
      cirrhosis epidemiology.
AB  - We estimated the validity, i.e., whether the diagnostic criteria were fulfilled
      for the patients registered with the diagnosis of liver cirrhosis in a Danish
      hospital discharge registry, and the completeness, i.e., whether all patients
      with liver cirrhosis were included in the registry. Information in the regional
      hospital discharge registry in the Country of Aarhus, Denmark was compared with
      hospital records and information in a pathology registry. 85.4% of the patients
      registered with a diagnosis of liver cirrhosis fulfilled the diagnostic criteria
      for the diagnosis (validity). 93.2% of the patients registered with biopsy proven
      liver cirrhosis in the pathology registry were found in the discharge registry
      (completeness) with a diagnosis of liver cirrhosis. The hospital discharge
      registry showed relatively few misclassifications and the Danish National
      Registry of Patients (NRP), which is based on the regional registries, may
      provide a unique study base for future research.

PMID- 9172067
TI  - In search of controlled evidence for health care quality improvement.
AB  - The purpose of this study was to measure the efficiency of simple searches in
      retrieving controlled evidence about specific primary health care quality
      improvement interventions and their effects. Searches were conducted to retrieve
      evidence on seven interventions and seven effect variables. Specific words and
      the closest Medical Subject Headings (MeSH) recommended by professional
      librarians were used to search the MEDLINE database. Searches were restricted to
      the MeSH publication type "randomized controlled trial." Two reviewers
      independently judged retrieved citations for relevancy to the selected
      interventions and effects. In selecting MeSH terms, the average agreement among
      librarians was 64.3% (+/-26.1) for interventions and 57.1% (+/-19.9) for effects.
      Analysis of the 755 retrieved reports showed that MeSH term searches had an
      overall recall rate of 58% while the same rate for textword searches was
      significantly lower (11%, p < .001). The difference in overall precision rates
      was nonsignificant (26% versus 33%, p = .15). In the group of MeSH searches,
      overall precision and recall was significantly lower for effects than for
      interventions (12% versus 52%, p < .001 and 41% versus 69%, p < .001). Two
      textwords appeared in more than 25% of the benchmark collection: reminder (25.7%)
      and cost (25.0%). The results of this study indicate that information needs for
      health care quality improvement cannot be met by simple literature searches.
      Certain MeSH terms and combinations of textwords yield moderately efficient
      recall and precision in literature searches for health care quality improvement.
      Clinicians and physician executives gaining direct access to bibliographic
      database could probably be better served by structured indexing of critical
      aspects of randomized controlled clinical trials: design, sample, interventions,
      and effects.

PMID- 9172068
TI  - Logics and logistics of community intervention against osteoporosis: an evidence
      basis.
AB  - Under designations like small areas action research and intervention, directed
      'ground-up' health promotion and prevention in the population form an important
      part of the ongoing medical systems development. There is recent evidence of the
      success of community intervention against cardiovascular disease. In
      osteoporosis, however, there is still a lack of conclusive data on both the
      logics and logistics of such an approach. Since 1988, a county health policy
      program has been formulated and implemented in Ostergotland, Sweden, following
      the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n
      approximately 7,600) was chosen for a local and generalizable osteoporosis
      prevention project mediated by the primary care organization by means of health
      promotion and education in the community. In the present report we emphasize that
      community intervention is an important new advancement of the medical systems,
      where the basic research questions include operational and management aspects as
      equally vital and measurable requisites and results as other performance and
      outcome variables. We found that a community intervention trial against
      osteoporosis is both motivated and feasible and in this report wish to provide
      evidence on these crucial issues of logics and logistics.

PMID- 9172069
TI  - Implementation of a patient charting system: challenges encountered and tactics
      adopted in a burn center.
AB  - The rapid movement of information technologies into health care organizations has
      raised managerial concern regarding the capability of today's institutions to
      satisfactorily manage their introduction. Indeed, several health care
      institutions have consumed huge amounts of money and frustrated countless people
      in wasted information systems implementation efforts. Unfortunately, there are no
      easy answers as to why so many health informatics projects are not more
      successful. In this light, the aim of this study is to provide a deeper
      understanding of how clinical information systems are being implemented by
      emphasizing research efforts on the dynamic nature of the process, that is, the
      "how" and "why" of what happened. Using a case study methodology, we examined the
      implementation of a patient charting system in the Burn Center of a large, not
      for-profit, teaching hospital. Based on an in-depth examination of this
      implementation, several insights are offered to those who have responsibility for
      managing complex and risky clinical information system implementation projects.

PMID- 9172070
TI  - The in vitro motility activity of beta-cardiac myosin depends on the nature of
      the beta-myosin heavy chain gene mutation in hypertrophic cardiomyopathy.
AB  - Several mutations in the beta-myosin heavy chain gene cause hypertrophic
      cardiomyopathy. This study investigates (1) the in vitro velocities of
      translocation of fluorescently-labelled actin by beta-myosin purified from soleus
      muscle of 30 hypertrophic cardiomyopathy patients with seven distinct beta-myosin
      heavy chain gene mutations: Thr124Ile, Tyr162Cys, Gly256Glu, Arg403Gln,
      Val606Met, Arg870His, and Leu908Val mutations; and (2) motility activity of beta
      myosin purified from cardiac and soleus muscle biopsies in the same patients. The
      velocity of translocation of actin by beta-myosin purified from soleus or cardiac
      muscle of 22 normal controls was 0.48 +/- 0.09 micron s-1. By comparison, the
      motility activity was reduced in all 30 patients with beta-myosin heavy chain
      gene mutations (range, 0.112 +/- 0.041 to 0.292 +/- 0.066 micron s-1. Notably,
      the Tyr162Cys and Arg403Gln mutations demonstrated significantly lower actin
      sliding velocities: 0.123 +/- 0.044, and 0.112 +/- 0.041 micron s-1,
      respectively. beta-myosin purified from soleus muscle from four patients with the
      Arg403Gln mutation had a similar actomyosin motility activity compared to beta
      myosin purified from their cardiac biopsies (0.127 +/- 0.045 micron s-1 versus
      0.119 +/- 0.068 micron s-1, respectively). Since these seven mutations lie in
      several distinct functional domains, it is likely that the mechanisms of their
      inhibitions of motility are different.

PMID- 9172071
TI  - Fish muscle cytoskeleton integrity is not dependent on intact thin filaments.
AB  - Striated muscle cytoskeleton was studied by ultrastructure and electrophoresis.
      Treatment of sea bass white muscle myofibrils and glycerinated fibres with
      calpain caused disruption of costameres, intermediate filaments, and Z-line,
      without altering sarcomeres. V8 protease also caused loss of costameres and Z
      line, and disrupted sarcomeres without affecting the intermediate filaments.
      Recombinant lipase caused loss of Z-lines and also sarcolemma detachment, without
      changing sarcomeres or intermediate filaments. DNase-1 removed thin filaments and
      partially removed Z-lines while leaving intact the sarcolemma attachments and
      intermediate filaments. Calpain, V8 protease, lipase and DNase-1 treatments
      induced extensive loss of alpha-actinin from the Z-line, which could be related
      to titin cleavage (calpain, V8), phosphoinositide hydrolysis (lipase), and actin
      depolymerisation (DNase-1). These results show that the cytoskeletal components
      are independent of intact thin filaments.

PMID- 9172072
TI  - Smooth muscle myosin light chain kinase is transiently expressed in skeletal
      muscle during embryogenesis and muscle regeneration both in vivo and in vitro.
AB  - By using a polyclonal antibody raised against smooth muscle Myosin Light Chain
      Kinase of adult chicken we show that the 135 kDa smooth muscle Myosin Light Chain
      Kinase isoform is present in neonatal and regenerating rat skeletal muscle, as
      well as in adult atrial myocardium. No reaction was evident in adult skeletal
      muscle fibres. In neonatal and in early regenerating muscle smooth muscle Myosin
      Light Chain Kinase is associated with embryonic myosin as revealed by their co
      presence in muscle fibres. Experiments in vitro show the same results in
      myotubes. In atrial myocardium there is a patchy positivity in certain group of
      myocytes. Immunoblotting experiments show in muscle cell cultures, in neonatal
      and in regenerating skeletal muscle a protein band with electrophoretic mobility
      corresponding to that of smooth muscle Myosin Light Chain Kinase. These results
      suggest that the expression of smooth muscle Myosin Light Chain Kinase is not
      fully tissue-specific and that regulation of the contractile machinery could be
      different during myogenesis and in adulthood, in relation to the peculiar dynamic
      characteristics of developing muscles.

PMID- 9172073
TI  - Osmotic 'detubulation' in frog muscle arises from a reversible vacuolation
      process.
AB  - Isolated Rana temporaria sartorius muscle fibres were subject to introduction and
      subsequent withdrawal of 400 mM extracellular glycerol, exposures to high
      divalent ion concentrations and then cooling. Tubular detachment was then
      assessed through changes in the action potential afterdepolarization. (1) The
      rapid (5-10 min) rather than slow cooling step (30 min) produced a gradual (30
      min) development of detubulation arrested by the subsequent replacement of
      glycerol and reversed by addition of 350 mM sucrose. Such osmotic agents
      influenced neither resting potentials of intact or detubulated fibres nor action
      potentials in intact fibres. (2) Full tubular detachment was achieved by 40 min.
      Laser epifluorescence microscopy demonstrated an accompanying tubular vacuolation
      through its trapping of a Rhodamine dye. (3) Subsequent re-additions (at 10-80
      min) of glycerol restored the afterdepolarization in 30% of detubulated fibres
      and correspondingly reduced vacuolation. Sustained (> 60 min) exposures to 350 mM
      sucrose, applied between 30-60 min, both reversed tubular isolation in 70% of
      detubulated fibres and abolished tubular vacuolation. Finally, results from
      transient (10-30 min) sucrose exposures resembled the consequences of sustained
      applications of glycerol, suggesting that detubulation and its reversal result
      from an osmotic mechanism. (4) Nevertheless, irreversible changes developed after
      70-80 min in 70% of detubulated fibres, a process hastened by slow cooling steps
      in the initial osmotic stress. The present study thus correlates morphological
      and electrophysiological consequences of applying osmotic shock to skeletal
      muscle for the first time. It additionally differentiates reversible and
      irreversible components of detubulation. Finally, it suggests that detubulation
      results from the similarly reversible vacuolation observed under comparable
      osmotic conditions, and that such vacuolation can eventually lead to irreversible
      detubulation.

PMID- 9172074
TI  - Ca(2+)-induced conformational shift of the COOH-domain of eel skeletal muscle
      troponin C in the presence of physiological concentrations of Mg2+.
AB  - The spectroscopic properties of Trp152 of eel skeletal muscle troponin C have
      been studied under conditions in which the COOH-domain is depleted of metal ions,
      titrated with Mg2+ and subsequently with Ca2+. This spectroscopic study clearly
      shows that the Mg2+ or Ca(2+)-bound states substitution lead to distinct
      conformations of the COOH-domain. The analysis of eel troponin C absorption and
      Trp152 fluorescence emission spectra indicates a more polar environment in the
      Mg(2+)-bound state of the protein. Steady state tryptophan polarization and
      lifetime distribution data indicate that the motion of the indole moiety is more
      restricted in the Mg2+ state of the protein than in the Ca(2+)-bound state.
      However, fluorescence quenching data using I- and Cs+ show that Trp152 is more
      accessible to the solvent in the Mg(2+)-bound state of eel troponin C. This
      spectroscopic analysis of the distinct Ca2+ and Mg(2+)-bound states of eel
      troponin C is consistent with the description of the three-dimensional structure
      of the corresponding states of pike (pI = 4.10) parvalbumin which is structurally
      homologous to the COOH-domain of troponin C. Since it appears that during
      muscular contraction, magnesium ions, which occupy the binding sites of the COOH
      domain of troponin C in the resting cell are replaced by calcium ions, the
      structural shift occurring upon Mg2+/Ca2+ substitution, must have a physiological
      significance. The role of this domain is probably not limited to a structural
      role.

PMID- 9172075
TI  - Contractility and myosin isoform compositions of skeletal muscles and muscle
      cells from rats treated with thyroid hormone for 0, 4 and 8 weeks.
AB  - The effects of 4 and 8 weeks of thyroid hormone (3,5,3'-triiodothyronine, T3)
      treatment on skeletal muscles of young (3-6 months) male Wistar rats were
      investigated in the present study. In the slow-twitch soleus, contraction and
      half-relaxation times of the isometric twitch were significantly shorter in
      hyperthyroid rats than in the control group, and twitch duration was shorter in
      rats treated with T3 for 8 weeks than for 4 weeks. All single soleus muscle
      fibres from hyperthyroid rats co-expressed types I and IIA myosin heavy chains
      (type I/IIA fibres) or type I, IIA and IIX myosin heavy chains (type I/IIAX
      fibres), while only type I MyHC fibres were isolated from the controls. A
      significantly higher content of type IIA myosin heavy chain and fast myosin light
      chain isoforms was observed in soleus fibres from the 8-week than from 4-week T3
      group. There was no significant difference in maximum velocity of unloaded
      shortening (V0) between type I myosin heavy chain fibres from controls (1.12 +/-
      0.46 muscle lengths s-1, n = 48) and type I/IIA myosin heavy chain fibres from
      the 4-1.09 +/- 0.36 muscle length s-1, n = 33) and 8-week (1.03 +/- 0.31 muscle
      lengths s(-1), n = 31) groups, but type I/IIAX fibres from the 8-week T3 group
      had significantly higher V0 (1.56 +/- 0.10, n = 5) than type I from control and
      type I/IIA from hyperthyroid rats. In the fast-twitch extensor digitorum longus,
      neither myosin isoform composition, twitch duration nor V0 was affected by 4 or 8
      weeks of T3 exposure. In conclusion, a dramatic and exposure duration-dependent
      change in the contractile speed of the isometric twitch and the expression of
      fast myosin isoforms was observed in soleus, but not in extensor digitorum
      longus, in response to T3 treatment. Long-term T3 treatment had relatively less
      influence, however, on V0 at the single cell level in spite of the dramatic
      increase in fast myosin isoforms.

PMID- 9172076
TI  - Interaction between titin and thin filaments in intact cardiac muscle.
AB  - A 'freeze break' technique and immunoelectron microscopy were used to study the
      elastic properties of cardiac titin filaments. Small bundles consisting of a few
      fibres from freshly prepared dog papillary muscle were quickly frozen and broken
      under liquid nitrogen to fracture sarcomeres in planes perpendicular to the
      filament axes. Breaks occurred at each of several regions along the sarcomeres.
      The still-frozen specimens were thawed during fixation to allow elastic filaments
      to retract. The broken muscle segments were then treated with monoclonal titin
      antibody 9D10 which labelled a unique epitope in the I-band. In sarcomeres broken
      at the A-I junction, the titin filaments reacted toward the Z-line, independently
      of the thin filaments. The retracted epitopes did not reach the Z-line;
      retraction stopped at the N1-line level. In sarcomeres broken near the Z-line,
      the titin filaments retracted in the opposite direction, to the tip of the thick
      filaments. When the break occurred in the A-band, by contrast, the titin-epitope
      position was unaffected. On the basis of these results, and despite the reported
      interaction of titin and actin in vitro, it appears that cardiac titin molecules
      form elastic filaments that are functionally independent of the thin filaments.
      Near the Z-line, however, the titin filaments seem to associate firmly with the
      thin filaments.

PMID- 9172077
TI  - L-type calcium current activation in cultured human myotubes.
AB  - The time course of activation of the skeletal muscle L-type calcium channel was
      studied in voltage-clamped myotubes derived from human satellite cells. The slow
      L-type current was isolated by inactivating faster calcium current components
      using appropriate prepulses or by subtracting the currents not blocked by 5
      microM nifedipine. The L-type current exhibited a single exponential activation
      and time constants which showed little voltage dependence in the range +10 to
      +50mV. Currents blocked by nifedipine could be partially restored by UV-light
      flash photolysis. When a flash of light was applied during a depolarizing step,
      the activation time course of the resulting inward current contained a rapid,
      almost instantaneous component followed by a slower component. The amplitude of
      the rapid component was different when the flash was applied at different times
      during the depolarizing step: depolarization first increased and then decreased
      the fraction of channels which could rapidly be restored from the block by
      photolysis. Plotted versus time after the onset of the depolarization this
      fraction closely matched the time course of the L-type current obtained before
      the block by nifedipine. This indicates that the slow gating recations of the
      Ca2+ channel remain functional in the nifedipine-blocked state. Large
      conditioning depolarizations which had been shown to enhance the speed of L-type
      current activation in frog muscle fibres showed no effect in human myotubes.
      Numerical simulations using a gating scheme proposed for frog muscle demonstrate
      that such differences can be caused by changing just a single kinetic parameter.

PMID- 9172078
TI  - Fibre type-specific and nerve-dependent regulation of myosin light chain 1 slow
      promoter in regenerating muscle.
AB  - The regulation of a slow muscle gene, the myosin light chain 1 slow/ventricular
      gene, has been studied by in vivo transfection into regenerating rat skeletal
      muscle. Constructs containing portions of the myosin light chain 1
      slow/ventricular promoter linked to reporter genes were injected into fast and
      slow muscles 3 days after muscle injury by bupivacaine injection, and reporter
      gene activity was analysed after 10 days. We report that a sequence in the 5'
      flanking region of the myosin light chain 1 slow/ventricular gene is able to
      direct slow muscle-specific regulation of reporter genes, and that the expression
      of the transgene, like that of the corresponding endogenous gene, is dependent on
      intact nerve. This study validates the use of regenerating muscle as a model for
      studying muscle gene regulation and is the first demonstration of a myosin gene
      promoter regulated by nerve activity.

PMID- 9172079
TI  - Contraction and relaxation in the absence of a sarcoplasmic reticulum: muscle
      fibres in the small pelagic tunicate Doliolum.
AB  - Previous ultrastructural observations suggested that Doliolum muscle fibres
      apparently lacked both sarcoplasmic reticulum and transverse tubular-system.
      External Ca2+ is required for contraction, caffeine does not evoke contraction,
      nor does it increase intracellular Ca2+ level. Ryanodine at 50 microM has no
      effect on electrically-evoked contractions. Further, electrical stimulation in
      external solutions lacking Na+ leads to sustained contracture. We conclude that
      intracellular Ca2+ stores are absent in these rapid obliquely-striated fibres,
      and that reduction in internal Ca2+ levels following contraction depends upon
      Na(+)-Ca2+ exchange across the sarcolemma.

PMID- 9172080
TI  - Polymerization of myosin on activation of rat anococcygeus smooth muscle.
AB  - The in vivo state of assembly of myosin in vertebrate smooth muscle is
      controversial. In vitro studies on purified smooth muscle myosin show that it is
      monomeric (10S) under relaxing conditions and filamentous under contraction
      conditions. Electron microscopic and antibody labelling studies of intact smooth
      muscles, on the other hand, suggest that myosin is filamentous in the relaxed as
      well as the contracting state and that 10S myosin occurs only in trace amounts.
      However, birefringence, conventional EM and X-ray diffraction evidence suggests
      that in certain smooth muscles in vivo (e.g. rat anococcygeus), while myosin
      filaments exist in the relaxed state, their number increases on contraction.
      Here, we have used low temperature electron microscopic techniques (rapid
      freezing followed by freeze-substitution), which preserve labile components in
      close to their in vivo state, to detect any change in filament number on
      contraction. The results from rat anococcygeus have been compared with those from
      guinea pig taenia coli, in which other techniques have revealed no change in
      filament number. In the anococcygeus, we find evidence for a 23% increase in
      filament density in transverse sections of contracting muscle compared with
      relaxed muscle. In the taenia coli we find no change. These results are in
      qualitative agreement with earlier findings. They provide evidence for
      polymerization of myosin in contracting rat anococcygeus, and suggest that this
      process is subtle and occurs only in some smooth muscles.

PMID- 9172082
TI  - Stillbirth after occupational exposure to N-methyl-2 pyrrolidone.

PMID- 9172083
TI  - Is there a standardized questionnaire for obtaining an occupational history?

PMID- 9172081
TI  - The amino acid sequence of the light chain of Acanthamoeba myosin IC.
AB  - The amino acid sequence of the light chain of Acanthamoeba myosin IC deduced from
      the cDNA sequence comprises 149 amino acids with a calculated molecular weight of
      16,739. All but the 3 N-terminal residues were also determined by amino acid
      sequencing of the purified protein, which also showed the N-terminus to be
      blocked. Phylogenetic analysis shows Acanthamoeba myosin IC light chain to be
      more similar to the calmodulin subfamily of EF-hand calcium-modulated proteins
      than to the myosin II essential light chain or regulatory light chain
      subfamilies. In pairwise comparisons, the myosin IC light chain sequence is most
      similar to sequences of calmodulins (approximately 50% identical) and a squid
      calcium-binding protein (approximately 43% identical); the sequence is
      approximately 37% identical to the calcium-binding essential light chain of
      Physarum myosin II and approximately 30% identical to the essential light chain
      of Acanthamoeba myosin II, and the essential light chain and regulatory light
      chain of Dictyostelium myosin II. The sequence predicts four helix-loop-helix
      domains with possible calcium-binding sites in domains I and III, suggesting that
      calcium may affect the activity of this unconventional myosin. This is the first
      report of the sequence of an unconventional myosin light chain other than
      calmodulin.

PMID- 9172084
TI  - Whole-body vibration exposure and occupational work-hardening.

PMID- 9172085
TI  - Cost-effectiveness of the influenza vaccine in a healthy, working-age population.
AB  - To determine if the influenza vaccine can reduce absenteeism and the cost of
      Influenza-Like Illness (ILI) in healthy adults in the workplace, a prospective,
      non-randomized, non-placebo control trial was done in six North Carolina textile
      plants. One hundred thirty-one vaccinated employees were compared with 131 age-
      and gender-matched non-vaccines from different plants. Twenty-six (20%) of the
      vaccinated and 64 (49%) of the unvaccinated group had ILI (P = 0.0000008).
      Fifteen (11%) of the vaccinated and 31 (24%) of the unvaccinated employees missed
      work because of ILI (P = 0.01). There were 43 lost workdays in vaccinated and 93
      in unvaccinated employees (P = 0.00004). The "cost per saved lost workday" was
      $22.36, for a company savings of $2.58 per dollar invested in the vaccination
      program. We concluded that the influenza vaccine can give significant reductions
      in incidence, absenteeism, and cost associated with ILJ in the workplace.

PMID- 9172086
TI  - A state-based surveillance system for work-related asthma.
AB  - The current national surveillance system for occupational illnesses
      underestimates the incidence of work-related asthma. This article describes a
      state-based surveillance system for work-related asthma. The Michigan
      surveillance system enables us to estimate the incidence of work-related asthma,
      describe the characteristics of affected individuals, and facilitate public
      health interventions in the form of workplace inspections. The data presented are
      based on interviews with a case-series of individuals with work-related asthma
      reported to the Michigan Department of Public Health (MDPH) from 1988 to 1994. We
      also present cross-sectional data on coworkers of the index cases, who were
      interviewed during the workplace investigations, and exposure measurements from
      those investigations. Potential cases were reported by physicians, hospitals, or
      the Michigan Department of Labor. Case eligibility was based on the criteria for
      work-related asthma developed by the National Institute for Occupational Safety
      and Health (NIOSH). Between 1988 and 1994, 725 people who met the NIOSH criteria
      for work-related asthma were reported to the MDPH. Seventy-six percent of the
      reports were from physicians, 17.1% were from hospitals, 7.3% were from workers'
      compensation records, and 3.5% were from other health professionals. Eighty-three
      percent of the reports were for individuals with the onset of newly diagnosed
      asthma after a period of symptomless exposure, 7.3% were for aggravation of
      preexisting asthma, and 9.5% were for reactive airway dysfunction syndrome
      (RADS). The overall annual average incidence rate of work-related asthma in
      Michigan was 2.9 cases per 100,000 workers. Rates were 0.8/100,000 in the service
      industry and 8.5/100,000 in manufacturing. Isocyanates and machining coolants
      were the two most common causes of asthma among workers reported to the
      surveillance system. Demographics of the individuals reported are described.
      During workplace follow-up investigations, 861 fellow workers were identified as
      having possible work-related asthma. Another 151 coworkers were identified from
      the company-maintained injury and illness logs as having possible work-related
      asthma. In addition, the investigations identified two new causes of work-related
      asthma. The primary limitations of the surveillance system include a lack of
      objective testing to confirm the diagnosis of work-related asthma and
      underreporting of cases. Despite these limitations, this state-based surveillance
      system has proven successful in identifying new cause of asthma and identifying
      workplaces with a high prevalence of workers with respiratory symptoms who may
      benefit from public health interventions.

PMID- 9172087
TI  - Curvilinear relationship between blood lead level and reaction time. Differential
      association with blood lead fractions derived from exogenous and endogenous
      sources.
AB  - Prior studies demonstrate an inconsistent relationship between occupational
      inorganic lead exposure and simple reaction time (SRT) performance. In this
      study, we administered a computerized SRT test to 78 currently employed lead
      smelter workers and then investigated the relationship between different measures
      of blood lead and components of SRT performance. The measures of blood lead
      included current blood lead (PbB) and mathematically derived blood lead fractions
      from the environment (PbB-env) and from bone (PbB-bn). Measures of SRT
      performance, obtained from 44 trials with interstimulus intervals (ISIs) ranging
      from 1 to 10 seconds, included median SRT (SRT-md), mean SRT for ISIs between 1
      and 5 seconds (SRT-1-5), and mean SRT for ISIs between 6 and 10 seconds (SRT-6
      10). Multiple regression analysis after adjustment for age and education revealed
      a curvilinear relationship between PbB and SRT-md. As PbB increased from 0 to 30
      micrograms dl-1, SRT-md decreased, and only with PbB levels above 30 micrograms
      dl-1 did SRT-md increase. PbB terms accounted for 13.7% of the variance in this
      SRT measure (P < 0.01). The longer ISI variable, SRT-6-10, was found to be more
      strongly related to PbB, to have lesser variability across ISIs, and to be
      unrelated to age. Additional multiple regression analysis to examine the
      relationship between components of SRT and the PbB fractions, PbB-env and PbB-bn,
      showed only PbB-env to account for significant variance in SRT-md, (14.4%, P <
      0.01), SRT-1-5 (9.7%, P < 0.03), and SRT-1-6 (15%, P < 0.01). We conclude that
      the relationship between PbB and SRT is U-shaped, that the SRT measure SRT-6-10
      has properties that make it the preferred measure of SRT performance in future
      studies, and finally that only PbB-env, and not PbB-bn, is related to components
      of SRT.

PMID- 9172088
TI  - Historical cohort mortality study of a continuous filament fiberglass
      manufacturing plant. I. White men.
AB  - An historical cohort mortality study of a continuous filament fiberglass
      manufacturing plant was undertaken to determine whether an elevated lung cancer
      risk would be observed on a cohort basis. A nested case-control study of white
      male lung cancer deaths was incorporated into the study design. An interview
      survey to obtain information on sociodemographic factors, including smoking, and
      an historical environmental reconstruction to identify elements in the plant
      environment to which workers might be exposed were included in the study design.
      Respirable glass (Beta) fibers were produced only from 1963 to 1968. The lung
      cancer odds ratio (OR) among those workers exposed to respirable glass fibers is
      below unity, as are ORs for exposure to asbestos, refractory ceramic fibers,
      respirable silica (except for the lowest exposure level), total chrome and
      arsenic. There is a suggestion of an increase with exposure among smokers only
      for exposure to formaldehyde, although the OR for the highest level is based on
      only one case and is not likely to be meaningful. None of these plant exposures
      suggests an increase in lung cancer risk for this population. Although the lung
      cancer standardized mortality ratios are slightly elevated, results of the case
      control investigation confirm that neither respirable glass fibers nor any of the
      substances investigated as part of the plant environment are associated with an
      increase in lung cancer risk for this population.

PMID- 9172089
TI  - Convenience store robberies in selected metropolitan areas. Risk factors for
      employee injury.
AB  - Circumstances of injury were abstracted from police reports for 1835 convenience
      store robberies that occurred during 1992 or 1993 in selected metropolitan areas
      of seven eastern states. Subset analyses were performed using the data (758
      robberies) from four states with relatively complete risk factor information. The
      purpose of this study was to estimate the risk of injury in a robbery situation
      for various risk factors. The overall risk of employee robbery-related injury
      could not be estimated because the probability of robbery is unknown. Of the 1835
      robberies, 59% of the total robberies occurred at nighttime (9 p.m. to 3 a.m.),
      47% occurred in stores previously robbed in the study period, 63% involved the
      use of a firearm, and 12% were associated with an injury to at least one
      employee. In the subset analysis of 758 robberies in four states, the employee
      probability of injury in a robbery was lower with firearm use compared with no
      weapon or use of a blunt instrument, and the probability of severe injury
      (defined as death, or an injury necessitating a trip to a hospital) was lower
      with a firearm compared with the use of a blunt instrument. However, all five
      fatalities were firearm-related. Other factors that were associated with a lower
      probability of employee injury included robbery occurrence in stores that had
      been robbed multiple times, compared with stores robbed only once; having 1 to
      999 dollars stolen, compared with having no money stolen; and the presence of a
      customer(s) in the store at the time of the robbery. The employee risk of injury
      was not significantly different between one- (0.106) and multiple-employee
      (0.111) stores. Similarly, the employee risk of severe injury was not
      significantly different between one- (0.029) and multiple-employee stores
      (0.022). We conclude that there are several potential risk factors for employee
      injury in convenience store robberies, some of which are amenable to
      interventions. Further research on these factors and their relationship to
      employee injury is indicated.

PMID- 9172090
TI  - A mortality study of oil refinery and petrochemical employees.
AB  - Results from a prospective mortality surveillance of 3803 refinery and
      petrochemical workers at a Shell Oil Company facility in Louisiana are presented.
      This report includes employees who worked more than 6 months before January 1,
      1994 and pensioners who were alive as of January 1, 1973. Vital status was
      ascertained through 1993. Regardless of the comparison population used to
      calculate expected numbers (United States, Louisiana, or the surrounding tri
      parish area), significantly fewer deaths were observed for all causes combined,
      all malignant neoplasms, heart disease, nonmalignant respiratory disease, and
      cirrhosis of the liver among male employees after 10 or more years' latency. With
      the United States as comparison, the all causes combined standardized mortality
      ratio (SMR) was 0.72 (95% confidence interval [CI] = 0.65 to 0.79), and the SMR
      for all cancer was 0.75 (95% CI = 0.61 to 0.92). The brain cancer rate for this
      group was nonsignificantly increased, with five observed deaths and three
      expected deaths, whereas mortality from leukemia was consistently lower than
      expected. The overall favorable mortality experienced by employees at this
      refinery and chemical plant is probably a result of a combination of factors,
      such as the healthy worker effect, relatively low risks related to the workplace,
      and the beneficial effects of continuing employment.

PMID- 9172091
TI  - Illness absence at an oil refinery and petrochemical plant.
AB  - Results from a prospective illness-absence surveillance of refinery and
      petrochemical workers from 1986 through 1994 are presented. Illness absence data
      for this study were extracted from the morbidity section of the Shell Oil
      Company's Health Surveillance System, which includes records of all illness
      absences in excess of 5 days. The majority of employees (59%) had no illness
      absence during the 9-year period studied. The 13% of the population who had three
      or more absences accounted for 63% of the total illness absence episodes and 62%
      of the total work days lost. Frequency rate and duration of absence increased
      with increasing age. The increased illness absence was associated with the
      presence of known health risk factors, such as smoking, elevated blood pressure,
      high cholesterol, and obesity. For example, obese women had a twofold increased
      illness absence rate compared with nonobese women and the rate for male smokers
      doubled that of nonsmoking men. These health risk factors are also more common
      among employees with three or more absences than those with fewer or no absences.
      The goal of this analysis is to quantify the impact of illness absence to develop
      disease prevention strategies to maximize good health in employees and to
      minimize both the frequency and duration of illness absence.

PMID- 9172092
TI  - Assessment of occupational risk for hantavirus infection in Arizona and New
      Mexico.
AB  - Differentiating occupational exposure from other potential domestic or
      recreational exposure(s) for Sin Nombre virus (SNV) infection is an epidemiologic
      challenge. Interviews on work-related activities were conducted, and serum
      specimens were obtained from 494 workers in Arizona and New Mexico. These workers
      may have been exposed to rodents and rodent excreta at work, but their primary
      occupation did not require rodent contact (National Park Service [n = 193];
      Navajo Agricultural Product Industry [n = 65], utility companies [n = 169] and
      plumbing and heating contractors [n = 67]. Within each occupational group (farm
      workers [n = 57], laborers [n = 20], professionals [n = 70], repairers [n = 211],
      service industry workers [n = 83], and technicians [n = 53], the majority of
      workers reported working in areas that had rodent droppings (range, 75 to 95%);
      70% of laborers and 64% of service industry workers reported handling rodents.
      More than 60% of workers in each group, except technicians, reported reopening
      and cleaning or working in closed spaces. Approximately 90% of laborers,
      repairers, and farm workers reported hand-plowing. Although the risk for
      occupationally related SNV infection appears to be low, workers frequently
      performed risk activities associated with hantavirus pulmonary syndrome (HPS).
      All workers were seronegative for SNV by enzyme-linked immunoassay or Western
      blot testing. These findings, the known occupational exposure of some HPS cases,
      and the high HPS case-fatality rate (52%) support the need for recommendations to
      reduce human contact with rodents in the workplace. Increased understanding of
      hantavirus transmission to humans will help focus future recommendations to
      minimize human exposures effectively.

PMID- 9172093
TI  - Recommended library and electronic resources for occupational and environmental
      physicians. ACOEM Committee report. American College of Occupational and
      Environmental Medicine.

PMID- 9172094
TI  - Photochemical stability of the inclusion complexes formed by modified 1,4
      dihydropyridine derivatives with beta-cyclodextrin.
AB  - The results of studies of photochemical stability of the derivatives of 1,4
      dihydropyridine (NR) are reported. The NR with various substituents (-NO2, -Cl, 
      F, CF3) at different positions in the phenyl ring were identified by UV
      spectrophotometry. Photodegradation of NR in the inclusion complexes with beta
      cyclodextrin (beta-CD) was studied in the liquid phase. The rate of
      photodegradation of NR derivatives was dependent on the position of -NO2 group in
      the phenyl ring; for the ortho isomer it is ten times higher than for the meta
      one. The rate of photodegradation of 2-NO2-NR (ortho isomer) in inclusion complex
      with beta-CD was 200 times slower than that for this compound in the crystal
      phase. In the case of halogeno- and cyanoderivatives, the presence of beta-CD
      caused a 4-fold increase in the photodegradation rate.

PMID- 9172095
TI  - Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound.
AB  - A pharmaceutical active compound H appears in two polymorphs, A and B, that are
      stable below and above room temperature, respectively. The A- and B-forms were
      found to have distinct FT-Raman spectra, in particular for a band at 1716 cm-1 (A
      form) or 1724 cm-1 (B-form). Mixtures of A- in B-form were prepared, and the
      relative intensity of the characteristic bands at 1716 and 1724 cm-1 was found to
      be proportional to the relative amounts of A- and B-form in the mixtures. A
      calibration was made which was linear in the range from 1.8 to 15.4% (w/w) of A-
      in B-form. The results were compared with other methods for analysis of
      polymorphs: FT-IR spectrometry, differential scanning calorimetry, and powder X
      ray diffractometry. A novel FT-Raman sample presentation method for inhomogeneous
      samples is presented.

PMID- 9172096
TI  - Measurement of uncertainty and discrimination limit in purity tests of drug
      quality.
AB  - Because of baseline fluctuation in an instrumental analysis, a purity test can
      overlook an illegitimate drug which contains an undesirable substance in more
      amount than a prescribed reference value. This paper proposes a probability
      theory to predict the lowest (average) signal, E[Y2], of the substance which can
      be discriminated from the (average) reference signal, E[Y1], with a high
      probability (here, 95%) in liquid chromatography (LC). The difference between the
      lowest signal and reference signal, E[Y2]-E[Y1] (> 0), is referred to here as a
      discrimination limit. The repetition of experiments to estimate the standard
      deviation of measurements is unnecessary for the probability theory, but a
      mathematical treatment of instrumental baselines (Fourier transform, etc.) is
      essential. The Monte Carlo simulation is carried out in which the reference
      signal and predicted signal for the discrimination limit are overlaid randomly
      5000 times on real LC baselines. The result is satisfactory: the observed
      probability for the right answer is 94.3 or 94.8%; the theoretical one is 95%.
      The normality of the measurement distribution is examined for LC and capillary
      electrophoresis to verify the fundamental assumption of the proposed theory.

PMID- 9172097
TI  - Selectivity optimization for the separation of chlorophenols in an irregularly
      shaped experimental region in capillary electrophoresis.
AB  - The separation of seventeen chlorophenol congeners and phenol was studied as a
      function of several variables. The pH and the concentration of sodium
      dodecylsulphate (SDS) were found to be important. During the implementation of a
      central composite design for the optimization of the separation it appeared that
      a part of the domain was not feasible as it resulted in very long migration times
      and extremely deformed peaks. Therefore, a D-optimal design was selected within
      the boundaries of the feasible region. The optimization of the selectivity did
      not result in selective regions for a simultaneous separation. It was, however,
      possible to find a region for the simultaneous separation of 15 compounds.
      Further optimization at these optimal conditions resulted in a separation where
      17 peaks could be observed.

PMID- 9172098
TI  - Single pump column switching technique employing a flow gradient and wavelength
      programmed fluorescence for simultaneous monitoring of serotonin, fluoxetine and
      norfluoxetine in rat brain microdialysate.
AB  - A single pump column switching technique with multidimensional chromatography,
      flow gradient and wavelength programmed fluorescence detection was developed for
      simultaneous quantitation of serotonin, fluoxetine and norfluoxetine in rat brain
      microdialysate. The column switching was configured such that position I of the
      switching valve employed column I (50 mm length) and column II (250 mm length) in
      series. This configuration resulted in optimal resolution of serotonin from
      interfering neurochemicals from rat brain. After elution of serotonin at 13.2 min
      the valve was switched to position II in which the flow of the mobile phase was
      directed through column I only. Flow gradient programming was then used to ramp
      the flow rate from 0.1 to 0.4 ml min-1 which resulted in optimal elution of
      fluoxetine and norfluoxetine. Strategic optimization of the single mobile phase
      enabled use of a single pump and detector making the analytical system simple and
      cost effective. Wavelength programmed fluorescence enabled sensitive detection of
      the analytes despite the difference in their fluorescence spectrum. The limit of
      detection for serotonin, norfluoxetine and fluoxetine were 10, 612 and 523 fmol,
      respectively. Rat brain microdialysate samples demonstrated selectivity for
      serotonin, fluoxetine and norfluoxetine. The method demonstrates application to
      the study of site specific neuropharmacokinetics and neuropharmacodynamics of
      fluoxetine in vivo.

PMID- 9172099
TI  - Determination of U-89968E, a 5HT1a agonist in rat plasma using solid-phase
      extraction, precolumn derivatization and reversed-phase high-performance liquid
      chromatography.
AB  - A selective and sensitive HPLC method was developed for the determination of U
      39968E in rat plasma. The assay involved solid-phase extraction of the analyte
      and the internal standard and precolumn derivatization with cyclohexane-1,3-dione
      reagent before injection on to the HPLC column. The samples were chromatographed
      on a Spherisorb S5 CN column (25 cm x 4.6 mm i.d.) with a mobile phase containing
      acetonitrile-trifluoroacetic acid-water (17:0.2:83, v/v/v) at a flow rate of 1.5
      ml min-1. The column eluent was monitored by flourescence detection with
      excitation at 272 nm and emission at 320 nm. The assay is linear over the range 4
      759 ng ml-1. The relative standard deviation at the limit of quantification, 4 ng
      ml-1, was 7.1%. This method was successfully applied to the determination of U
      89968E in rat plasma during pharmacokinetic studies.

PMID- 9172100
TI  - A tandem solid phase extraction, reversed-phase HPLC method for determining SDZ
      WAG 994 in dog, monkey and rat blood.
AB  - The development and validation of a sensitive and specific HPLC method for SDZ
      WAG 994 (I) in dog, monkey and rat blood is described. Sample preparation
      entailed double solid phase extraction (SPE) of I and the internal standard from
      0.5 ml of animal blood using a phenyl and propyl sulfonic acid cation exchange
      column, sequentially. Chromatographic separation was achieved on a YMC Basic C-8
      narrowbore HPLC column and the eluates were detected by UV absorption at 266 nm.
      The method has a linear response up to at least 1800 ng/ml with a limit of
      quantification of 1 ng/ml across all species. Analysis of 'blinded' quality
      control dog and monkey blood samples over 3 or 4 days produced median precisions
      of 2.89 and 4.77%, and median reproducibilities of 4.86 and 10.9%, respectively.
      Curve fitting of variability estimates indicated that concentration independent
      error contributed 3-9% of the total method error for the tandem SPE procedure.
      Extracted endogenous material from blood matrices, several potential metabolites
      and cyclohexyladenosine were well resolved from the peaks of interest. The
      stability of I in dog blood stored at -20 degrees C is at least 6 months. The
      overall absolute and relative recovery of I using the tandem SPE procedure was
      85.5 +/- 5.1% and 96.5 +/- 5.0%, respectively. The ruggedness of the method has
      been demonstrated by multiple analyses, from several toxicokinetic studies,
      performed by different analysts using comparable instrumentation.

PMID- 9172101
TI  - Determination of morphine and codeine in plasma by HPLC following solid phase
      extraction.
AB  - A cheap simple and rapid extraction procedure followed by a UV high performance
      liquid chromatography (HPLC) assay is described for the simultaneous
      determination of morphine (M) and codeine (C) in plasma. The method is based on
      extraction of these opiates from plasma using reversed phase (solid phase)
      extractions columns followed by HPLC with UV detection at 240 nm. The extraction
      step provides, respectively, 85 and 80% recovery for M and C. The response of the
      detection system is linear for both molecules in the studied range from 50 to 750
      ng ml-1. No other drugs have been found to interfere with the assay. This method
      offers a quick, cost effective and reliable procedure for specifically
      determining M and C, from a small sample volume.

PMID- 9172102
TI  - Rapid stereospecific high-performance liquid chromatographic determination of
      levofloxacin in human plasma and urine.
AB  - A rapid high-performance liquid chromatographic (HPLC) method for the
      determination of levofloxacin in human plasma and urine has been validated. A
      single-step liquid-liquid extraction procedure was used to isolate levofloxacin
      from the biological matrix prior to quantitative analysis. The compound was
      separated on an Inertsil C18 reversed-phase HPLC column and quantified by
      measuring the UV absorbance at 330 nm. The stereospecificity was achieved in the
      ligand-exchange mode by incorporating chiral reagents directly into the HPLC
      mobile phase. Ciprofloxacin was used as the internal standard. The method was
      linear from 0.08 to 5.18 micrograms ml-1 of levofloxacin in plasma and from 23 to
      1464 micrograms ml-1 in urine. The overall utility of the method is reflected in
      its high sample throughput and easy adaptability to robotic automation, thus
      making the procedure suitable for pharmacological and pharmacokinetic studies of
      levofloxacin.

PMID- 9172104
TI  - A chemical assessment and HPLC assay validation of bulk paromomycin sulfate.

PMID- 9172103
TI  - Determination of 4-hydroxyifosfamide in biological matrices by high-performance
      liquid chromatography.
AB  - A high-performance liquid chromatographic method has been developed for the
      determination of 4-hydroxyifosfamide, a metabolite of ifosfamide, in plasma of
      cancer patients. The analyte is derivatized to 7-hydroxyquinoline, which can be
      detached fluorimetrically. The calibration graph is linear in the concentration
      range 0.05-25 microM, the limit of detection being 40 nM. Any inference from
      acrolein, another metabolite of ifosfamide, was ruled out. 4-Hydroxyifosfamide is
      very unstable in plasma and a stabilization procedure by adding citric acid has
      been developed. Thus treated, the samples were stable for 4 days. Analysis of a
      patient's plasma samples revealed that the 4-hydroxifosfamide concentration did
      not exceed 10 microM.

PMID- 9172105
TI  - Stability of vitamin C derivatives in solution and topical formulations.
AB  - The stability of ascorbic acid, ascorbyl palmitate and magnesium ascorbyl
      phosphate (VC-PMG) in both standard solutions and topical formulations was
      investigated by direct RP-HPLC analysis after sample dilution with a suitable
      aqueous-organic solvent mixture. The results showed that, whereas the two vitamin
      C derivatives were more stable than ascorbic acid, the ascorbyl esters showed
      significant differences. Esterification with palmitic acid in 6 position did not
      prevent hydrolysis of the molecule, either in solution or in emulsion; only the
      special preparation of products with high viscoelastic properties was able to
      reduce the typical behaviour of this compound. Conversely, the introduction of
      the phosphoric group in 2 position protected the molecule from break-up of the
      enediol system, confirming VC-PMG as a very stable derivative of vitamin C that
      may be easily used in various types of cosmetic products.

PMID- 9172106
TI  - HPLC resolution of C5 chiral 4,5-dihydro-1,4-benzodiazepines: stereochemical
      characterization and enantioselective GABAA receptor binding.
AB  - HPLC resolution on chiral stationary phases has been successfully employed to
      obtain single enantiomers of C5 chiral 4,5-dihydro-1,4-benzodiazepines and to
      determine the enantiomeric composition of the collected stereoisomeric fractions.
      The absolute configuration of the prevailing enantiomer has been assigned on the
      basis of the circular dichroism spectra, as compared with that of the structural
      analogue (5R)- and (5S)-dihydrodiazepam. The single enantiomers, assayed for
      their binding to the central nervous system receptor, showed relatively low
      affinity but significant differences in displacing radioactively labelled
      flunitrazepam from specific benzodiazepine site. GABA shift experiments allowed
      the classification of these benzodiazepines as partial agonist or antagonist.

PMID- 9172107
TI  - An analytical methodology to quantify the incorporation of enzymes in
      polyalkylcyanoacrylate nanoparticles based on size exclusion chromatography.
AB  - The performances of different methods of quantification of protein (methods based
      on direct spectrophotometric and spectrofluorimetric analysis, chemical reactions
      and liquid chromatography) to quantify the amount of enzyme incorporated into
      polyalkylcyanoacrylate nanoparticles, were compared. A methodology based on size
      exclusion chromatography was selected. The performances of the analytical method
      to quantify the enzymes L-asparaginase and superoxide dismutase in different
      polymerization media of poly-isobutilcyanoacrylate, were evaluated. The
      quantification of superoxide dismutase in the presence of esterase, enzyme used
      to solubilize nanoparticles, was attempted. An adequate separation between enzyme
      and the other components of polymerization media was achieved, so the selectivity
      of the method is adequate to the quantification of an enzyme in polymerization
      medium, either before or after polymerization. Although lack of selectivity of
      the column to separate enzymes was observed. The retention time of L-asparaginase
      and superoxide dismutase in polymerization medium are, respectively, 7.4 and 7.5.
      Linear correlation between peak area and enzyme concentration were observed for
      both enzymes in the concentration range from 10 to 80 micrograms ml-1, either
      before or after polymerization and in different polymerization media. This SE
      HPLC analytical methodology is adequate to determine the degree of incorporation
      of enzymes in polyalkylcyanoacrylate nanoparticles as evidenced by the linear
      responses of the chromatographic method, the reproductibility of repeated sample
      injections and the precision of the quantification of enzyme concentration.

PMID- 9172108
TI  - Behaviour of resolution by changing solvent strength and selectivity in the
      'PRISMA' model using reversed-phase HPLC for biogenic amines.
AB  - The retention behaviour of 17 dansylated biogenic amines in 6 linear gradients at
      13 solvent combinations, expressed by the selectivity points (Ps) according to
      the 'PRISMA' model, was investigated. The dependence between the retention times
      (tr) and different gradients was examined. Three dimensional resolution (Rs) maps
      for each peak-pair in the different gradients at the 13 selectivity points were
      constructed, and the affect of the gradients on separation were investigated. The
      study showed that the dependence between the gradients and tr values of dansyl
      amides can be expressed using quadratic functions with a high degree of accuracy.
      These functions are well suited for estimating the resolution in different
      gradients and Ps. The three dimensional Rs maps clearly demonstrated the changes
      between the different gradients and Ps. This was of considerable benefit when
      searching the optimum mobile phase by changing both the solvent strength (ST) and
      selectivity.

PMID- 9172109
TI  - Comparison of quantitative high performance thin layer chromatography and the
      high performance liquid chromatography of parabens.
AB  - A method is described for the densitometric determination of the p-hydroxybenzoic
      esters and p-hydroxybenzoic acid in mixtures or in drugs. This method is compared
      with the one used in high performance liquid chromatography (HPLC). The
      calibration curves were linear in interval 0.250-3.60 mumol ml-1 per 200 nl per
      spot. The limit of detection and the relative standard deviation (RSD) are higher
      than in HPLC (RSD is 6% in HPTLC. 3% in HPLC; limit of detection about 40 pmol in
      HPTLC and 25 pmol in HPLC) but HPTLC quantitative determination of parabens in
      drugs is faster.

PMID- 9172110
TI  - Analysis of aporphine and quinolizidine alkaloids from Caulophyllum thalictroides
      by densitometry and HPLC.
AB  - High-performance liquid chromatographic (HPLC) and densitometry procedures were
      developed to determine the principal alkaloids in the roots of C. thalictroides.
      In both techniques the alkaloids content was assessed using cytisine as an
      internal standard. The purity and identity of the peaks of the alkaloids was
      examined by diode array detection and by comparison with the standards. The
      content of individual alkaloids was found to be in the range 0.02-1.1% w/w.

PMID- 9172111
TI  - Flow injection amperometric determination of L-dopa, epinephrine or dopamine in
      pharmaceutical preparations.

PMID- 9172112
TI  - Occupational health monitoring using solid phase extraction of urine.

PMID- 9172113
TI  - Laparoscopy. Gasless vs. CO2 pneumoperitoneum.
AB  - OBJECTIVE: To compare gasless laparoscopy with conventional laparoscopy using CO2
      pneumoperitoneum. STUDY DESIGN: Women undergoing bilateral laparoscopic tubal
      coagulation (LTC) were randomly assigned to one of two laparoscopy procedures:
      (1) a gasless laparoscopy system consisting of an intraabdominal fan retractor
      and electrically powered mechanical arm, and (2) standard CO2 pneumoperitoneum
      laparoscopy. The two laparoscopic procedures were compared on the basis of
      intraoperative visualization, operation duration, procedural difficulty,
      ventilatory parameters, hemodynamic stability, and postoperative pain and nausea.
      RESULTS: Significant disadvantages for the surgeon (increased technical
      difficulty, poorer visualization, longer operative times) and patient (greater
      postoperative pain and nausea) were seen with the gasless system. Because of
      these findings, the study was prematurely terminated after only 18 patients had
      participated. Intraoperative ventilatory and hemodynamic parameters were more
      stable in the gasless laparoscopy groups; however, the differences were not
      clinically significant in this population of healthy patients. CONCLUSION: The
      markedly increased technical difficulty and absence of clear clinical benefits
      for the healthy patient led to the conclusion that laparoscopy with CO2
      pneumoperitoneum is preferable for routine LTC and most laparoscopic procedures
      in the pelvis. Gasless laparoscopy may be of benefit for the fragile patient with
      a compromised cardiovascular system who may suffer complications from
      hypercarbenemia.

PMID- 9172114
TI  - Twin zygosity. Automated determination with microsatellites.
AB  - OBJECTIVE: Twin zygosity determinations can be performed with anthropologic,
      serologic and genetic markers; however, these methods are more than occasionally
      inefficient, often expensive and sometimes inaccurate. We used microsatellites as
      DNA markers and developed a largely automated, rapid and efficient method of
      determining zygosity. STUDY DESIGN: We used five highly polymorphic short tandem
      repeat loci, coamplified by polymerase chain reaction (PCR) using fluorescence
      labeled primers. Thirty-six samples were simultaneously analyzed by
      electrophoresis and laser detection. The PCR products were sized by automated
      fragment analysis. RESULTS: We typed 132 pairs of monozygotic (MZ) and dizygotic
      (DZ) twins. With five markers, the probability that any twin pair was MZ if all
      markers were concordant was 99%. CONCLUSION: This method is a rapid and reliable
      approach to zygosity detection.

PMID- 9172116
TI  - Overcoming unsatisfactory colposcopy. Use of osmotic dilators.
AB  - OBJECTIVE: To evaluate the usefulness of osmotic dilators as an alternative to
      diagnostic cone biopsy. STUDY DESIGN: Women who had an unsatisfactory colposcopic
      examination were offered repeat examination after use of osmotic dilators as part
      of an interventional, nonrandomized study. The physician selected the type, size
      and duration of use of the dilator. RESULTS: Twenty-nine of 32 women (91%)
      underwent a satisfactory repeat examination. Diagnostic cone biopsy was avoided
      in all women. Twenty-one women did not require further treatment, and four women
      had the lesion removed by the colposcopically directed biopsy. Six women
      underwent electrosurgery, and one woman underwent cryotherapy. CONCLUSION: The
      use of osmotic dilators can decrease the need for diagnostic cone biopsy.

PMID- 9172115
TI  - High-risk obstetric patients. Maternal morbidity after cesareans.
AB  - OBJECTIVE: To assess maternal morbidity associated with cesarean delivery among
      high-risk obstetric patients in a private practice setting. STUDY DESIGN:
      Maternal outcome parameters were prospectively studied in 1,000 consecutively
      delivered patients over a one-year period. RESULTS: Three hundred forty-one
      patients (34%) delivered by cesarean; 194 of the procedures were performed
      without labor. The incidence of febrile morbidity and wound infection in patients
      undergoing cesarean delivery without labor, 0.5%, was no greater than that of
      patients who delivered vaginally (P = 1.0). There was a higher incidence of
      transfusion in patients delivered by cesarean without labor, but these patients
      were more likely to have preoperative anemia (P = .036). Patients undergoing
      cesarean with labor or ruptured membranes had an increased incidence of both
      febrile morbidity (P = .023) and wound seroma (P = .008). CONCLUSION: Maternal
      morbidity following cesarean delivery in high-risk obstetric patients in a
      private practice setting is low.

PMID- 9172117
TI  - Maternal thrombocytopenia. Predicting neonatal thrombocytopenia with
      cordocentesis.
AB  - OBJECTIVE: To evaluate the efficacy of cordocentesis for predicting fetal
      thrombocytopenia in the presence of maternal thrombocytopenia. STUDY DESIGN: We
      studied platelet counts obtained by cordocentesis from 42 consecutive immune
      thrombocytopenia purpura patients. Platelet counts were obtained on 36 neonates,
      and the statistical analysis included only these infants. Presence of maternal
      antiplatelet antibodies, interval from fetal sampling to delivery, neonatal
      platelet counts and outcome were evaluated. Thrombocytopenia was defined as a
      platelet count < or = 150,000/microL, with < or = 50,000 microL considered
      severe. RESULTS: No procedure-related complications occurred. A moderate
      correlation existed between fetal and neonatal platelet counts (r = .48, P =
      .003), unrelated to the interval between sampling and delivery. Eight of 36
      fetuses had thrombocytopenia, and 4 were confirmed at delivery. Two neonates had
      thrombocytopenia at birth but not at cordocentesis. Two neonatal thrombocytopenia
      cases were severe. Neither was categorized as severe antenatally. The
      sensitivity, specificity, and positive and negative value for predicting severe
      neonatal thrombocytopenia were 0%, 100%, 0%, and 94%, respectively. Grade 1
      intraventricular hemorrhages occurred in two neonates delivered at 35 weeks' with
      normal platelet counts. CONCLUSION: Cordocentesis was not reliable in predicting
      severe neonatal thrombocytopenia; however, the high negative predictive value was
      reassuring. The clinical utility of the technique and the population in which it
      should be used remain to be defined.

PMID- 9172118
TI  - Elevated serum Chlamydia trachomatis IgG antibodies. What do they mean for IVF
      pregnancy rates and loss?
AB  - OBJECTIVE: To evaluate the impact of elevated serum Chlamydia IgG antibodies (Ab)
      on in vitro fertilization (IVF) outcome in a large infertility population. STUDY
      DESIGN: One hundred ninety-four women under 40 years of age undergoing a total of
      316 IVF cycles were evaluated. All couples with positive serum Chlamydia IgG Ab
      were pretreated with doxycycline, 100 mg twice daily, for 10 days prior to the
      first IVF cycle. RESULTS: One hundred seven women (55.2%) had elevated serum
      Chlamydia IgG Ab. One hundred seventy-two IVF cycles (54.4%) were in patients
      with elevated Ab as compared to 144 cycles (45.6%) in controls with negative Ab.
      There were no significant differences in mean age, number of mature oocytes
      obtained or number of embryos transferred between the two groups. Patients with
      elevated IgG Ab had on ongoing pregnancy rate of 30.2% (52/172) and implantation
      rate of 13.5% (101/746) as compared to 34.7% (50/144) and 13.6% (88/649) in the
      negative Ab group, respectively (P = NS for both). Two ectopic pregnancies
      occurred in the elevated Ab group (1.2%, 2/172) vs. none in the negative Ab
      group. The incidence of early pregnancy loss was 8.7% (15/172) and 9.7% (14/144)
      in the positive and negative Ab groups, respectively (P = NS). CONCLUSION: The
      prevalence of elevated serum Chlamydia IgG Ab in patients presenting for IVF was
      higher than in the general population. In the absence of an active genital tract
      infection, the presence of elevated serum Chlamydia IgG Ab was not associated
      with a poor IVF outcome when couples were treated with antibiotics prior to
      stimulation. In addition, there was no correlation between IVF outcome and
      quantitative IgG Ab titers in women with elevated serum Chlamydia Ab. We
      recommend that all couples with elevated titers be treated with doxycycline prior
      to the first IVF attempt to optimize pregnancy rates and minimize infectious
      complications.

PMID- 9172119
TI  - Pain during early abortion.
AB  - OBJECTIVE: To determine which factors predict pain perception in women undergoing
      first-trimester abortion under local anesthesia. STUDY DESIGN: Women undergoing
      first-trimester abortion with local anesthesia were asked about their perception
      of pain during the procedure and at the time of discharge from the recovery room.
      They were also asked to compare the amount of pain experienced to their expected
      amount of pain. Additional data were abstracted from the patient record. RESULTS:
      During the study period, 1,055 women had abortions and had records suitable for
      analysis. Factors that were not found to be related to pain were the operating
      physician, maximal amount of cervical dilatation, size of the suction cannula,
      prior abortion and prior pelvic examination. Gestational age did not show a
      consistent relationship to pain, although there was a suggestion that pain
      perception increases at the highest gestational ages. Longer procedures and
      procedures following the use of osmotic dilators tended to have higher pain
      scores. Prior abdominal delivery did not have a significant relationship to pain
      score, but prior vaginal delivery correlated with decreased pain by any method of
      analysis. The difference in pain perception between women with and those without
      prior vaginal birth was most striking at the earliest gestational ages.
      CONCLUSION: Prior vaginal delivery was the most consistent predictor of decreased
      pain perception during first-trimester abortion. Future studies on discomfort
      during abortion should include gestational age, patient age and the route of
      prior deliveries.

PMID- 9172120
TI  - Beta-thalassemia major and successful pregnancy.
AB  - OBJECTIVE: To conduct a study of maternal and fetal outcome in pregnant women
      with transfusion-dependent beta-thalassemia major. STUDY DESIGN: The course and
      outcome of pregnancy were studied prospectively in 32 pregnant women with
      transfusion-dependent beta-thalassemia major, of which 10 were HIV 1 positive, at
      Sanjay Gandhi Hospital, Manipur, India, from January 1990 to July 1996. RESULTS:
      Over a period of six years, 32 women with transfusion-dependent beta-thalassemia
      major conceived. Twenty conceptions were spontaneous (63%), and 12 (37%) followed
      induction of ovulation. There were 24 (75%) singleton vaginal deliveries, all of
      which were term. At term, eight (25%) women delivered by elective cesarean
      section due to cephalopelvic disproportion. All the women remained well
      throughout pregnancy. Despite increased blood transfusion requirements during
      pregnancy to maintain the hemoglobin level > 10 g/dL, serum ferritin levels
      remained stable in all patients. CONCLUSION: Successful outcomes of pregnancy
      occurred in some women with transfusion-dependent beta-thalassemia major.

PMID- 9172121
TI  - Tobacco use for identifying pregnant women at risk of substance abuse.
AB  - OBJECTIVE: To examine the effectiveness of current smoking status as a rapid
      screening tool to identify pregnant women at risk of heavy alcohol and/or illicit
      drug use. STUDY DESIGN: Women (N = 92) seeking prenatal care were interviewed to
      assess lifetime and recent tobacco, alcohol and illicit drug use. Rates of recent
      heavy alcohol and illicit drug use were compared in current smokers and
      nonsmokers. RESULTS: All subjects reporting recent heavy alcohol and/or illicit
      drug use were current smokers; none were nonsmokers. CONCLUSION: Obstetric
      screening of pregnant women for current smoking status seems to be a cost
      effective method of identifying those at risk of antepartum heavy alcohol and/or
      illicit drug use.

PMID- 9172122
TI  - Retained surgical needle in the perineum. Report of a case with a novel method of
      search and rescue.
AB  - BACKGROUND: Retrieval of a broken or lost surgical needle can be a difficult
      task, often requiring extensive surgical exploration. CASE: A surgical needle was
      retained in the perineum. Needle-hookwire placement with biplane fluoroscopy
      allowed the precise localization and marking of the foreign body; surgical
      removal without extensive exploration was therefore possible. CONCLUSION: The use
      of needle-hookwire localization with biplane fluoroscopy should be considered for
      retrieval of foreign bodies in the perineum.

PMID- 9172123
TI  - Successful pregnancy after bilateral hypogastric artery ligation. A case report.
AB  - BACKGROUND: Selective embolization of the hypogastric arteries is an effective,
      nonsurgical alternative for the management of obstetric and gynecologic
      hemorrhage. Successful pregnancy following bilateral hypogastric artery occlusion
      has been reported, but experience is extremely limited. CASE: We report a case of
      successful pregnancy in a patient previously treated with bilateral hypogastric
      artery embolization. Although a diminution of fetal growth toward term was
      observed, the fetus tolerated labor and subsequently thrived, without sequelae.
      CONCLUSION: This case supports the possibility of normal labor for women who
      conceive after bilateral hypogastric artery embolization.

PMID- 9172124
TI  - Hyperbaric oxygen treatment during pregnancy in acute carbon monoxide poisoning.
      A case report.
AB  - BACKGROUND: Carbon monoxide poisoning in pregnancy is a relatively rare
      occurrence, with potentially serious complications for both mother and fetus.
      Controversy regarding treatment during pregnancy exists primarily due to the
      concern for oxygen toxicity in the fetus. However, rapid oxygen dissociation and
      prolonged clearance of carbon monoxide in the fetal circulation emphasize the
      importance of adhering to aggressive treatment protocols. CASE: A 22-year-old
      employee at an office undergoing repairs on the heating and ventilation systems
      presented with neurologic symptoms, tachycardia, tachypnea, signs of preterm
      labor and a carboxyhemoglobin level that was mildly elevated. Fetal monitoring
      demonstrated a reactive nonstress test with mild to moderate repetitive variable
      decelerations. The patient underwent hyperbaric oxygen treatment, with complete
      resolution of her neurologic symptoms, tachycardia and tachypnea as well as fetal
      variable decelerations. She was additionally treated with intravenous magnesium
      sulfate tocolysis, with cessation of contractions. The patient subsequently
      delivered at term; the viable infant had no sequelae of in utero carbon monoxide
      poisoning. CONCLUSION: This case supports previously published recommendations
      for treating acute carbon monoxide poisoning during pregnancy with hyperbaric
      oxygen. As more cases are gathered, a more widely accepted set of standards can
      be established.

PMID- 9172125
TI  - Interstitial pregnancy managed medically. A case report.
AB  - BACKGROUND: Interstitial pregnancies are often associated with significant
      morbidity. The surgical treatment of such ectopic gestations often requires
      laparotomy and cornual resection, thus obliterating tubal and uterine continuity.
      Methotrexate has been shown to be 94% successful in the management of tubally
      implanted ectopic gestations, but few reports describe its use in interstitial
      pregnancies. CASE: An 18-year-old woman who presented with an asymptomatic
      interstitial pregnancy was treated successfully with intramuscular methotrexate.
      Laparotomy and cornual resection were avoided. No adverse effects were noted.
      CONCLUSION: Interstitial pregnancies can be treated successfully with
      intramuscular methotrexate.

PMID- 9172126
TI  - Ovarian vein thrombosis during cesarean section. A report of two cases.
AB  - BACKGROUND: Puerperal ovarian vein thrombosis occurs in 0.2-0.5% of deliveries.
      It is usually thought to result from infection, but it has been hypothesized that
      thrombosis may occur as a primary event, and radiologic studies raise the
      possibility that ovarian vein thrombosis may occur quite frequently. CASES: Case
      1 had right ovarian vein thrombosis diagnosed at the time of nonemergency
      cesarean section for placenta previa. This was treated with ligation of the
      infundibulopelvic ligament above the level of the clot. Subsequent magnetic
      resonance imaging showed contralateral ovarian vein thrombosis, and therefore
      anticoagulant therapy was begun. The patient was asymptomatic. Case 2 had right
      ovarian vein thrombosis extending to the inferior vena cava diagnosed at elective
      repeat cesarean section. She was heparinized in the recovery room; subsequent
      ventilation/perfusion scan showed a probable pulmonary embolism. Both patients
      recovered uneventfully. CONCLUSION: These two cases demonstrate that ovarian vein
      thrombosis may occur as a primary event, in the absence of infection, and result
      in pulmonary embolism. Individualized management based on operative findings is
      recommended.

PMID- 9172127
TI  - Avian visual lateralization: a review.
AB  - Cerebral asymmetries represent an important principle of the organization of
      nervous systems. The asymmetries of the avian visual system, with their partly
      complementary domains in the left and the right hemisphere, offer an excellent
      window for the lateralized learning and cognitive processes. These behavioural
      experiments are accompanied by biochemical, synaptic, electrophysiological and
      neuroanatomical studies which have clarified to some extent the neuronal
      foundations of this asymmetry. Additionally they show that most, but not all,
      aspects of visual lateralization depend on a minute asymmetry of prehatch visual
      stimulation which triggers a cascade of events transforming the embryonic nervous
      system into lateralized structure and functioning.

PMID- 9172128
TI  - Monitoring nitric oxide (NO) in rat locus coeruleus: differential effects of NO
      synthase inhibitors.
AB  - A porphyrinic microsensor combined with in vivo voltammetry was used to monitor
      extracellular nitric oxide (NO) in the locus coeruleus (LC) of anaesthetized
      rats. Administration of N omega-nitro-L-arginine p-nitro-anilide (100 mg/kg, i.p)
      or 7-nitro indazole (30 mg/kg, i.p.), which both inhibit preferentially neuronal
      NO synthase (NOS), induced a marked decrease in the NO oxidation peak height. On
      the other hand, N omega-nitro-L-arginine methyl ester (L-NAME) (200 mg/kg, i.p.),
      a less selective NOS inhibitor, failed to decrease the NO signal. Moreover, intra
      LC administration of NMDA, known to activate LC noradrenergic neurones, increased
      the NO signal. This study demonstrates the usefulness of in vivo voltammetry to
      monitor basal levels of NO and their changes in the LC. Differential effects of
      NOS inhibitors show that their central activity need to be assessed through in
      situ measurement of NO before using these inhibitors as neuropharmacological
      tools.

PMID- 9172129
TI  - Dual cerebral processing of elementary auditory input in children.
AB  - We compared event-related responses (ERPs) to non-attended frequent and
      intermittent auditory input in school-aged children and in young adults. In
      adults, both inputs elicited prominent auditory N100 responses at vertex. In
      children, intermittent stimulation evoked vertex responses with similar latency
      and refractoriness, whereas frequently delivered identical tones evoked responses
      on average at 240 ms. Sensitization of a separate neuronal population at 260-300
      ms was obvious during intermittent stimulation in children. The dual behaviour,
      simultaneous 'habituation' of one neuronal population response and sensitization
      of another, may reflect the process of redirecting the attention and setting up a
      neuronal model. Furthermore, results suggest that a simplistic interpretation of
      developmental ERPs in which shortening of latencies represents maturation is
      insufficient.

PMID- 9172130
TI  - Desensitizing GABAC receptors on carp retinal bipolar cells.
AB  - Bicuculline- and baclofen-insensitive GABA receptors (GABAC receptors) on bipolar
      cells acutely dissociated from carp retina were investigated with using the whole
      cell patch-clamp recording technique. The currents of these cells mediated by
      GABAC receptors showed striking desensitization, even at low concentrations of
      GABA. Both the time constant tau of the GABAC current decay and the extent of
      desensitization were significantly different from that of GABAC receptors
      previously observed in other retinas and elsewhere in the CNS, suggesting that
      the GABAC receptors of carp bipolar cells might be distinct in intracellular
      mechanisms and subunit composition.

PMID- 9172131
TI  - Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue.
AB  - Oxidative stress is proposed to play a central role in the pathogenesis of
      amyotrophic lateral sclerosis (ALS). Anti-oxidant enzymes and DNA repair proteins
      are two major mechanisms by which cells counteract the deleterious effects of
      reactive oxygen species (ROS). Neurons may be particularly vulnerable to ROS
      induced oxidative DNA damage; this is repaired by the base-excision repair (BER)
      pathway. Frontal cortical levels and activity of the pivotal BER protein
      apurinic/apyrimidinic endonuclease (APE) were determined in 11 patients with
      sporadic ALS and six age-matched control subjects. APE levels (p < 0.003) and
      activity (p < 0.000007) were significantly lower in ALS subjects than in
      controls. These findings suggest that ALS brain tissue is inefficient in
      repairing oxidative DNA damage.

PMID- 9172132
TI  - Reversible hearing impairment induced by lithium in the guinea pig.
AB  - Lithium salts remain one of the most widely used treatments for depressive
      illness. The mechanisms involved probably include reduction in free inositol.
      Visual perceptive disturbances can be a side effect of the treatment. We report
      here for the first time that chronic lithium treatment in the guinea pig induces
      a predominantly low frequency hearing loss and, in the longer term, loss of
      sensitivity is observed across the whole audiogram. The changes are reversed when
      treatment is arrested. The observations could be accounted for, at least
      partially, by a lithium-induced perturbation of the phosphoinositide cascade
      within the inner ear.

PMID- 9172133
TI  - Phentermine/fenfluramine decreases cocaine self-administration in rhesus monkeys.
AB  - Dopaminergic agonists can decrease cocaine self-administration at doses that do
      not decrease food-maintained responding, a pre-clinical effect indicative of a
      potential treatment for human cocaine abuse. To assess whether similar effects
      could be obtained with medications currently used to treat substance abuse,
      phentermine and fenfluramine were given alone and in combination to rhesus
      monkeys responding under schedules of food and cocaine delivery. Phentermine
      decreased cocaine-maintained responding with no effect on food-maintained
      responding. Fenfluramine also selectively decreased cocaine-maintained
      responding, but only at the highest dose. Combining a lower dose of fenfluramine
      with phentermine selectively decreased cocaine-maintained responding, but not
      more than with phentermine alone. These results suggest that phentermine, as well
      as its combination with fenfluramine, may be useful in the treatment of cocaine
      abuse.

PMID- 9172134
TI  - Real-time detection of GABA-induced synaptic glutamate release in cultured rat
      cortex.
AB  - Glutamate is an important neurotransmitter in synaptic transmission. There are no
      methods, however, for continuous measurement of glutamate concentration at high
      temporal and spatial resolutions. We have developed a novel electrochemical
      detection method for the on-line measurement of glutamate release with nanomolar
      resolution in real time. Using this method, GABA was found to have a modulatory
      action on the synaptic glutamate release in cultured rat cortical cells. This
      synaptic modulation largely depends on the GABAA receptor and could be a key not
      only in neural development, but also in signal transduction in the brain. Our
      detection method is ideal for investigating such synaptic glutamate responses
      because of its higher sensitivity and real-time measurement capability.

PMID- 9172135
TI  - Stat1 in developing and adult rat brain. Induction after transient focal
      ischemia.
AB  - Stat1 has a dual function as signal transducer and activator of transcription,
      and is activated in response to growth factors and cytokines. We examined Stat1
      in the rat brain during development and following transient focal ischemia, using
      Western immunoblotting. Two bands of 91 and 84 kDa, corresponding to Stat1 alpha
      and Stat1 beta forms, were found with an intensity that increased from postnatal
      day 0 to adulthood in cerebellum and cerebral cortex. Ischemia caused a strong
      induction of Stat1 in the ipsilateral cortex after 4, 7 and 15 days, but not at 6
      or 24 h. These results show that Stat1 is normally expressed in the postnatal and
      adult rat brain and is induced under brain infarction.

PMID- 9172136
TI  - Rat gustatory memory requires protein kinase C activity in the amygdala and
      cortical gustatory area.
AB  - We have studied the physiological involvement of protein kinase C (PKC) in the
      formation of conditioned taste aversion (CTA) by means of microinjections of PKC
      inhibitors into the gustatory cortex (GC), amygdala (AMY) and thalamic gustatory
      area at various time-windows of the CTA paradigm. Rats injected between the CS-US
      interval with PKC inhibitors into the GC and AMY, but not into the thalamic
      gustatory area, failed to acquire CTA. Injections of PKC inhibitors 4 h after the
      US presentation or just before the retention test elicited no disruptive effect.
      Injections of PKC inhibitor into the AMY, but not into the GC, 30 min after the
      CS-US pairing impaired CTA formation. These results show that PKC activity in the
      GC and AMY has a key role in the acquisition phase of CTA, but not in the
      retrieval phase. The findings also suggest that the GC is concerned with
      information processing of the CS, and that the AMY is involved in the CS-US
      association.

PMID- 9172137
TI  - O2-sensitive K+ current in undifferentiated and NGF-treated PC12 cell variants.
AB  - It has been reported that cultured PC12 cells can be used as a model for studying
      mechanisms of O2 sensitivity, previously examined in peripheral chemoreceptors
      and some neurons. This study compared the hypoxic depression of K+ currents in
      two PC12 variants, before and after differentiation into neurone-like cells
      induced by nerve growth factor (NGF). The results show that interaction of O2 and
      K+ channels is strongly-voltage dependent in the PC12/TM but not the PC12/ES
      subline. In PC12/TM cells an effect of hypoxia on the K+ current was appreciable
      only at moderately depolarized voltages, with a loss of sensitivity at +40 to +50
      mV. NGF-induced transformation did not affect the responses seen in
      undifferentiated cells. These results emphasize the importance of screening PC12
      cells before selecting a variant for studying O2 sensitivity. In view of evidence
      cited in the literature that hypoxia may effect membrane channels directly,
      further molecular and biophysical studies of the differences among PC12 variants
      are required.

PMID- 9172138
TI  - Sodium butyrate decreases histamine-stimulated calcium mobilization in C6 glioma
      cells.
AB  - The aim of this study was to investigate the effect of sodium butyrate on calcium
      mobilization. Histamine was found to stimulate a dose-dependent increase in
      intracellular calcium concentrations ([Ca2+]i) through H1 receptors, but this
      effect was attenuated in C6 cells pretreated with 1-5 mM sodium butyrate.
      Evidence is provided that release of Ca2+ from intracellular stores is decreased
      in a dose-dependent manner. Experiments with BAPTA that show lower levels of
      [Ca2+]i in cells pretreated with higher concentrations of sodium butyrate suggest
      that sodium butyrate also decreases Ca2+ influx. These results suggest that
      changes in Ca2+ mobilization are at least partially responsible for sodium
      butylate-induced C6 cell differentiation.

PMID- 9172139
TI  - A natural peptide with NMDA inhibitory activity reduces tonic pain in the
      formalin model.
AB  - The aim of this study was to assess whether a natural peptide, histogranin,
      isolated from chromaffin cells and possessing NMDA receptor inhibitory activity,
      could reduce tonic pain. Rats received intrathecal injections of the stable
      analog [Ser1]histogranin (SHG), prior to induction of the formalin response. SHG
      markedly suppressed the second tonic phase of the formalin response compared with
      saline vehicle. A U-shaped dose-response curve was obtained. SHG had no effect on
      phase 1 acute pain responses. These findings indicate that SHG acts in a similar
      fashion as other, non-peptide, NMDA antagonists in suppressing tonic, but not
      acute pain. The presence of the natural peptide in chromaffin cells may
      contribute to the analgesic effects of adrenal medullary implants.

PMID- 9172140
TI  - Magnesium deficiency induces an hyperalgesia reversed by the NMDA receptor
      antagonist MK801.
AB  - The aim of this study was to determine the changes of the nociceptive thresholds
      in response to an acute mechanical stimulus (paw pressure) in magnesium (Mg)
      deficient rats, and the involvement of the NMDA receptor in these changes.
      Changes in vocalization thresholds was determined after 7 days of feeding with a
      Mg-depleted diet. Compared with the control group, Mg-deficient rats showed a
      significant decrease in the vocalization thresholds (-35.8 +/- 2.5%, p < 0.001)
      reflecting hyperalgesia. In Mg-deprived rats, three doses (0.06, 0.12 and 0.24
      mg/kg s.c.) of dizocilpine (MK801), a non-competitive NMDA receptor antagonist,
      significantly reversed the hyperalgesia in a dose-dependent manner for at least
      48 h. No effect of MK801 was observed in the control group. These data provide
      evidence that Mg deficiency could constitute a new model of hyperalgesia
      involving NMDA receptors.

PMID- 9172141
TI  - Cerebrovascular endothelial dysfunction mediated by beta-amyloid.
AB  - beta-Amyloid (A beta) toxicity has a critical role in the pathology of
      Alzheimer's disease (AD) but its function in the neurodegenerative process is not
      clearly established. Recently, we demonstrated a novel action of beta-amyloid on
      peripheral blood vessels: endothelial dysfunction through reactive oxygen
      species. Here we report the direct effect of A beta on cerebrovascular
      endothelium. Following treatment with A beta 1-40, bovine cerebral arteries
      showed characteristic features of endothelial dysfunction such as increased
      contraction to vasoconstrictor and diminished relaxation to endothelium-dependent
      vasodilators. Electron microscopy revealed significant damage to the endothelium
      by A beta. Pretreatment with the antioxidant superoxide dismutase (SOD) and PBN
      (n-tert-butyl-alpha-phenylnitrone) antagonized the effects of A beta. Endothelial
      damage induced by A beta could produce ischemic and inflammatory changes
      contributing to the pathology of AD.

PMID- 9172142
TI  - Prenatal ischemia reduces neuronal injury caused by neonatal hypoxia-ischemia in
      rats.
AB  - To determine whether 'ischemic tolerance', first described in adult rodents,
      exists in fetal and neonatal rats, a comparison of brain injury was made between
      two groups of rat pups following neonatal hypoxia-ischemia (HI). One group of rat
      pups had previously been subjected to HI in utero (HI + HI); the other had been
      subjected to a sham operation (SH + HI). Brain infarct size and neuronal injury
      were measured 24 h after the neonatal HI insult. As indicated by 2,3,5
      triphenyltetrazolium chloride staining and pathological examination, cerebral
      damage was significantly less in the HI+ HI group than in the SH + HI group.
      Induction of heat shock protein 70 (hsp70) was immunohistochemically detectable
      in both groups 24 h after the neonatal HI, and was proportional to the extent of
      tissue damage. The ischemic tolerance phenomenon observed in immature rats does
      not appear to be a result of induction of hsp70.

PMID- 9172143
TI  - Inflammation reveals inhibition of noxious responses of rat spinal neurones by
      carbamazepine.
AB  - The effect of subcutaneously administered carbamazepine, a sodium channel
      blocker, on the electrically evoked C-fibre (noxious) vs A beta-fibre (innocuous)
      responses of dorsal horn neurones in non-inflamed and inflamed rats (3 h after
      plantar injection of carrageenan) was studied. Carbamazepine (0.5-5 mg/kg)
      significantly reduced the noxious evoked responses of the neurones under
      inflammatory, but not non-inflamed, conditions. The innocuous evoked responses of
      the neurones were not sensitive to carbamazepine under any conditions and
      administration of the vehicle alone did not influence any evoked response of
      these neurones. We propose that there are changes in the type, or proportion of,
      sodium channels underlying the transmission of noxious messages following
      peripheral inflammation which become sensitive to carbamazepine.

PMID- 9172144
TI  - Eye position-dependent activation of neurones in striate cortex of macaque.
AB  - Extracellular recordings were made in the striate cortex in awake, behaving
      monkeys to test the influence of the eye position on cellular activity. Two
      monkeys (Macaca mulatta) were trained to fixate a small spot at 25 different eye
      positions. About half (52%) of the studied neurones showed a selective gaze field
      (GF). The cells' activities increased significantly when the monkey fixated at
      this field of view. For the majority of these neurones, GFs were located at the
      contralateral field of view with respect to the hemisphere from which responses
      were recorded, and were usually found a few degrees peripheral to the related
      receptive field. Eye position-dependent neurones were found at different depths
      of cortex, but mostly in the superficial layers. The results indicate that some
      neurones in striate cortex may code information about eye position and could
      contribute to target localization in a head-centred coordinate system by
      combining retinal and afferent eye position signals.

PMID- 9172145
TI  - Cao-sensing receptor (CaR)-mediated activation of K+ channels is blunted in CaR
      gene-deficient mouse neurons.
AB  - The extracellular Ca2+ (Cao)-sensing receptor (CaR) is expressed in hippocampus
      and other brain regions, suggesting that it could mediate some of the well
      recognized but poorly understood direct actions of Cao on neuronal function. This
      study presents evidence that the CaR is functionally coupled to Ca(2+)-activated
      K+ channels. The effects of CaR agonists on these channels in neurons from wild
      type (WT) and CaR-deficient (CaR -/-) mice were compared. Neomycin (100 mM) and
      elevation of Cao from 0.5 to 3 mM significantly increased the probability of
      channel opening (Po) in neurons from WT but not in those from CaR -/- mice. Thus
      the CaR activates neuronal K+ channels and could potentially inhibit neuronal
      excitability and neurotransmission via membrane repolarization.

PMID- 9172146
TI  - Face and shape repetition effects in humans: a spatio-temporal ERP study.
AB  - The neural bases of repetition effects for faces and non-significant shapes was
      studied using Mooneys' faces presented upright (face) or upside down (shape) with
      a repetition interval of 8 min 30 s-1. Scalp potentials and current density maps
      on 30 electrodes were compatible with an involvement of the infero-temporal and
      fusiform gyri (from 50 to at least 250 ms), mainly on the right, for both faces
      and shapes; the hippocampus and adjacent areas (around 300 ms), specifically for
      faces; the medial temporal lobes (450-650 ms) again independent of stimulus
      meaning. These results suggest that the facilitation of perception due to
      repetition involves both neocortical specialized areas and the medial temporal
      lobe, with different timings of activation. They further suggest that memory
      updating takes place more rapidly for faces than for meaningless shapes and that
      face recognition may be, at least partly, functionally encapsulated.

PMID- 9172147
TI  - A 100 amino acid region in the GABA rho 1 subunit confers robust homo-oligomeric
      expression.
AB  - Retinal gamma-aminobutyric acid type C (GABAC) receptors are believed to be
      composed of rho subunits. Although rho 1 and rho 2 are over 80% similar, the
      whole-cell currents generated by rho 1 receptors in Xenopus oocytes are
      significantly greater than those generated by rho 2 receptors. In this study,
      chimeric subunits containing different portions of human rho 1 and human rho 2
      were created to localize sequences facilitating robust rho 1 expression. Our
      results indicate that these sequences reside in a 100 amino acid domain in the N
      terminus of rho 1, and may involve N-linked glycosylation. Since the N-terminus
      also contains subunit assembly signals, rho 1 receptors may be formed more
      efficiently than rho 2 receptors. Therefore, this study furthers our
      understanding of the molecular basis of GABA-mediated inhibition in the retina.

PMID- 9172148
TI  - Subcellular localization of the alpha 7 nicotinic receptor in rat cerebellar
      granule cell layer.
AB  - The distribution of the alpha 7 nicotinic receptor subunit in the rat cerebellum
      was studied immunohistochemically at the electron microscope level using an alpha
      7 subunit-specific antibody. The granule cell layer showed a much lower level of
      immunoreactivity for the alpha 7 subunit than the Purkinje cell layer. Granule
      cell somata were completely devoid of labeling; this appeared to be restricted to
      glomeruli exclusively located in the membranes of granule cell dendrites. The
      alpha 7 immunolabeling was located not at active synaptic areas but was mostly
      perisynaptic. This localization suggests that nicotinic receptors containing the
      alpha 7 subunit could have a modulatory function and/or play a direct role in the
      generation of synaptic currents.

PMID- 9172149
TI  - Increased cerebral choline-compounds in Duchenne muscular dystrophy.
AB  - We investigated the hypothesis that cell membrane function is abnormal in brains
      of subjects with Duchenne muscular dystrophy (DMD) using proton-nuclear magnetic
      resonance (NMR) spectroscopy of human brain extracts. The total amount of choline
      containing compounds was significantly higher (about three times) than in normal
      controls and patients with other myopathies, while N-acetyl-L-aspartic acid and
      creatine were within the normal range. These findings indicate that abnormal cell
      membrane function may be correlated with the abnormal dystrophin or lack of
      dystrophin in the brain of patients with DMD.

PMID- 9172150
TI  - Acute adaptive changes in food intake pattern following olfactory ablation in
      rats.
AB  - We determined whether acute compensatory feeding pattern changes after bulbectomy
      persist on a chronic basis, or whether physiological adaptation occurs to
      normalize acute changes. Rats were randomized to olfactory bulbectomy or sham
      operation; all had jugular vein catheterization. Food intake, meal number and
      size were studied during infusion of parenteral nutrients providing 100% daily
      caloric intake (PN-100) to minimize post-ingestive effects. Rats were randomly
      assigned to acute (from day 14 after operation, PN-100 infused for 4 days,
      followed by 4 days of saline infusion) or chronic study (PN-100 infused for 4
      days from day 40, followed by 4 days of saline infusion). After olfactory
      ablation, acutely decreased meal size was offset by increased meal number, but 40
      days after, baseline differences between meal size and number no longer existed.
      No qualitative differences in response to PN-100 were noted between acute and
      chronic groups. Findings suggest a functional adaptation of food intake
      regulatory mechanism between 14 and 40 days after bulbectomy.

PMID- 9172151
TI  - Long-term alterations in growth factor mRNA expression following seizures.
AB  - Although alterations in growth factor mRNA occur during neuronal insults, little
      is known about the long-term effects of neuronal insults on growth factor
      expression. We have examined the effects of prolonged post-ictal times on the
      expression of Brain-derivered nerve factor (BDNF) and Neurotrophin 3 (NT3)
      following Kainic acid (KA)-induced seizures. In situ hybridization was performed
      on male Sprague-Dawley rats sacrificed 1-2 weeks following intracranial
      ventricular KA injections. BDNF mRNA increased bilaterally 1 and 2 weeks after
      injections, whereas NT3 mRNA decreased contralaterally 1 week and bilaterally 2
      weeks post-injection. These observations provide evidence that alterations in
      growth factor mRNA expression occur even after prolonged post-ictal recovery
      suggesting a possible role for growth factors in recovery and continued
      maintenance of surviving neurons within limbic seizure foci.

PMID- 9172152
TI  - p55 tumour necrosis factor receptors distribution in neuroblastoma cells.
AB  - p55 tumour necrosis factor receptors in neuroblastoma SKNBE cells were localized
      by immunofluorescence microscopy. They were detected at the surface on non
      permeabilized cells and, after differential permeabilization, in the Golgi area
      as diffuse staining and in the perinuclear region as clusters and punctuations.
      Intracytoplasmic punctuate forms were detected after permeabilization with Triton
      X-100, suggesting their location within organelles. Treatment with the
      differentiation-inducing agent all-trans retinoic acid (RA) greatly increased the
      cellular density of the immunoreactive receptors and receptors were detected in
      the newly formed neurites, suggesting that RA promoted their transport from the
      cell body. The results suggest direct influences on neuronal functions of tumour
      necrosis factor alpha released from adjacent or from target cells.

PMID- 9172153
TI  - Glycerol as a marker for post-traumatic membrane phospholipid degradation in rat
      brain.
AB  - Degradation of membrane phospholipids (PLs) is a well known phenomenon in acute
      brain injuries and is thought to underlie the disturbance of vital cellular
      membrane functions. In the present study glycerol, an end product of PL
      degradation, was examined in brain interstitial fluid as a marker of PL breakdown
      following experimental traumatic brain injury (TBI) using microdialysis. TBI was
      induced in artificially ventilated rats using the weight-drop technique. The
      trauma caused a significant, eight-fold increase of dialysate glycerol in the
      injured cortex, with the peak concentration in the second 10 min fraction after
      trauma. Glycerol then levelled off but remained significantly above sham-operated
      controls for the entire 4 h observation period in the perimeter of the injury
      region where scattered neuronal death is seen. The results support the concept
      that PL degradation occurs early after TBI and that interstitial glycerol,
      harvested by microdialysis, may be useful as a marker allowing in vivo monitoring
      of PL breakdown.

PMID- 9172154
TI  - A novel orally active group 2 metabotropic glutamate receptor agonist: LY354740.
AB  - Non-specific metabotropic glutamate receptor (mGluR) agonists have previously
      been shown to potentiate responses of spinal neurones to ionotropic glutamate
      receptor agonists. In this study we show that LY354740, which is a highly
      selective Group 2 mGluR agonist with nanomolar potency in vitro, also mimics the
      above effects following local ejection on spinal neurones in vivo, an action
      which is blocked by a Group 2 antagonist. Despite its polar nature, LY354740 is
      also active given either by the i.v. or the oral route (2.5-20 mg/kg) and thus
      will be a useful agent for investigating the role of Group 2 mGluRs both
      physiologically and clinically.

PMID- 9172155
TI  - HLA-DR antigens associated with major genetic risk for late-onset Alzheimer's
      disease.
AB  - Hla-dr antigen types were determined from DNA isolated from post-mortem brain
      tissue of age-matched groups of 78 patients with pathologically confirmed late
      onset Alzheimer's disease (AD) and 50 controls. The results suggest that for
      individuals with no apolipoprotein E epsilon 4 alleles the presence of either
      DR1, 2 or 3 antigens is associated with a significantly increased risk for
      development of late-onset AD. Conversely the DR4 or 6 antigens are associated
      with a decreased risk of similar magnitude. This DR effect, rather than prolonged
      use of non-steroidal anti-inflammatory drugs, could be responsible for the
      reported lower prevalence of AD in rheumatoid arthritis (a condition associated
      with an increased frequency of DR-4).

PMID- 9172156
TI  - Expression of tyrosine hydroxylase in newly differentiated neurons from a human
      cell line (hNT).
AB  - Previous studies have demonstrated that the synergistic interaction of acidic
      fibroblast growth factor (aFGF) and a number of co-activator molecules (dopamine,
      TPA, IBMX/forskolin) can induce the novel expression of the catecholamine
      biosynthetic enzyme tyrosine hydroxylase (TH) in non-TH-expressing neurons. To
      date, TH gene induction has been achieved only in cultures of primary brain
      neurons. In the present study, we investigated whether TH expression could
      similarly be induced in a cell line derived from human teratocarcinoma cells.
      Treatment with aFGF and its co-activators resulted in the prolonged expression of
      TH in newly differentiating human neurons (hNT) but not in their undifferentiated
      precursors (NT2). These findings suggest that hNTs may serve as a continual
      source of TH-expressing neurons for cell transplantation and developmental
      studies.

PMID- 9172157
TI  - Alpha isoform of calcium-calmodulin dependent protein kinase II (CAM II kinase
      alpha) restricted to excitatory synapses in the CA1 region of rat hippocampus.
AB  - Pre-embedding immunoperoxidase staining for CAM II kinase-alpha and post
      embedding immunogold staining for glutamate and GABA, were used to reveal the
      subcellular distribution of CAM II kinase-alpha at transmitter-characterized
      synapses in the CA1 region of rat hippocampus. Immunoelectron microscopy showed
      that the majority of CAM II kinase-alpha-immunostained neuronal profiles were
      dendritic spines presumably derived from pyramidal cells. CAM II kinase-alpha
      immunoreactivity was mainly localized in postsynatic densities associated with
      glutamatergic axon terminals. No CAM II kinase-alpha immunoreactivity was
      detected in GABA-immunoreactive profiles or at GABAergic synapses. This study
      provides morphological evidence that CAM II kinase-alpha is involved only in
      excitatory neuronal transmission in the CA1 region. The enzyme is unlikely to be
      involved in plasticity at GABA synapses.

PMID- 9172158
TI  - Optimization of liposome mediated transfection of a neuronal cell line.
AB  - A cell line derived from sensory neurons was transfected with high efficiency
      using cationic liposomes, formulated from 3 beta [N-(N',N'
      dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and dioleoyl L-alpha
      phosphatidylethanolamine (DOPE). This is the first time that cationic liposomes
      of this type have been reported to transfect a neuronal cell line. We used a
      reporter gene construct expressing beta-galactosidase under the control of the
      cytomegalovirus immediate early promoter and routinely observed transfection
      efficiencies > 40%. Parameters affecting transfection efficiency were examined
      and the ratio of DNA to liposome proved to be crucial. Liposome formulation
      procedures and cell transfection protocols devised here will be used as a basis
      for further in vivo and in vitro work.

PMID- 9172159
TI  - Response characteristics of cerebellar nuclear cells in the pigeon.
AB  - In birds, the output system of the cerebellum, the cerebellar nuclei, has not yet
      been studied electrophysiologically. Recordings from nuclear cells during
      electrical stimulation of the radial nerve revealed a uniform type of response
      consisting of an initial inhibition followed by a clear cut excitation. Responses
      with an initial excitation were rare. Response patterns and latencies suggest an
      input from Purkinje cells of the cerebellar cortex and a lack of collateral input
      from spinocerebellar pathways. This points to a fundamental difference from
      cerebellar nuclear cells in mammals, in which collateral input provides a
      prominent excitatory response under comparable experimental conditions.

PMID- 9172160
TI  - Presenilin 1 interaction in the brain with a novel member of the Armadillo
      family.
AB  - One approach to understanding the function of presenilin 1 (PS1), is to discover
      those proteins with which it interacts. Evidence for a function in developmental
      patterning came from C. elegans, in which a PS homologue was identified by
      screening for suppressors of a mutation in Notch/lin-12, a gene which specifies
      cell fate. However, this genetic experiment cannot determine which proteins
      directly interact with PS1. Therefore, we utilized the two hybrid system and
      confirmatory co-immunoprecipitations to identify a novel catenin, termed gamma
      catenin, which interacts with PS1 and is principally expressed in brain. The
      catenins are a gene family related to the Armadillo gene in Drosophila, some of
      which appear to have dual roles-they are components of cell-cell adherens
      junctions, and may serve as intermediates in the Wingless (Wg) signaling pathway,
      which, like Notch/lin-12, is also responsible for a variety of inductive
      signaling events. In the non-neuronal 293 cell line, PS1 interacted with gamma
      catenin, the family member with the greatest homology to Armadillo. Wg and Notch
      interactions are mediated by the Disheveled gene, which may form a signaling
      complex with PS1 and Wg pathway intermediates to regulate the function of the
      Notch/lin-12 gene.

PMID- 9172161
TI  - Sex differences in dopamine receptor overproduction and elimination.
AB  - Density of dopamine D1 and D2 family receptors was assessed using autoradiography
      in male and female rats from 25 to 120 days of age, focusing on transitions
      through puberty into full adulthood. Males had greater overproduction
      (approximately 4.6-fold) and elimination of striatal D1 and D2 receptors than
      females, though their adult densities were very similar. Males had more extensive
      overproduction of D1 receptors in nucleus accumbens and sustained a greater
      density into adulthood (57.8 +/- 21.2%). These results have implications for
      understanding gender differences in the prevalence of clinical disorders
      associated with dopamine.

PMID- 9172162
TI  - Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells.
AB  - The goal of this study was to investigate the effect of resveratrol, an active
      ingredient found in grapes and other plant products, in ameliorating oxidative
      stress. Oxidative stress was induced by addition of Fe2+ and t-butyl
      hydroperoxide to the cultured PC12 cell medium. Resveratrol, vitamins C and/or E,
      were added to the cell culture medium during oxidative stress. The combination of
      resveratrol and vitamins C and/or E was more effective in protecting the cell
      than was any of these three antioxidants alone.

PMID- 9172163
TI  - Contrasting forms of synaptic plasticity in monkey inferotemporal and primary
      visual cortices.
AB  - Activity-dependent synaptic plasticity was examined in vivo in two cortical areas
      of the adult monkey visual system, the primary visual and inferotemporal cortex,
      the first and late cortical stages essential for object recognition.
      Discontinuous high-frequency electrical stimulation of intrinsic horizontal
      connections in layer 2/3 caused contrasting forms of synaptic plasticity in the
      two areas. In the inferotemporal cortex, long-term potentiation of extracellular
      field potentials in layer 2/3 was induced, whereas in the same pathway of V1,
      identical stimulation protocol elicited long-term depression. The results
      indicate that susceptibility to synaptic plasticity varies among cortical areas
      in the monkey brain.

PMID- 9172164
TI  - Depolarization-induced slow potentiation of depolarizing afterpotential.
AB  - Effects of strong membrane depolarization on the excitability of regular spiking
      (RS) non-pyramidal cells in layer VI of the cat motor cortex were examined in in
      vitro slice preparations. RS non-pyramidal cells that expressed depolarizing
      afterpotential (DAP) following spikes displayed either of the two distinct
      responses: immediate and successive potentiation of DAP in association with
      repetition of firing, or slow enhancement of DAP after repetitive injections of
      strong depolarizing current pulses leading to burst firing. In those neurones
      that displayed the immediate potentiation of DAP, slow potentiation was never
      induced. This difference in changes of DAP was consistent with morphological
      differences. DAP-lacking RS non-pyramidal cells displayed neither immediate nor
      slow changes in excitability.

PMID- 9172165
TI  - Adenosine A2a receptors in the nucleus accumbens modulate prepulse inhibition of
      the startle response.
AB  - Prepulse inhibition (PPI) of the acoustic startle response (ASR) was disrupted by
      systemic administration of apomorphine (APO) (2 mg/kg, i.p.). Microinfusion of
      the selective adenosine A2a-recceptor agonist CGS21680 (0.05 microgram in 1.0
      microliter per side) into the nucleus accumbens (NAc), had no significant effect
      in animals with systemic vehicle pretreatment, but significantly reversed the
      disruption of PPI in rats pretreated with APO. Adenosine is, therefore, involved
      in the control of PPI through its actions on A2a receptors in the NAc. APO
      induced disruption of PPI is considered to represent an animal model useful for
      screening both typical and atypical antipsychotic agents. The present results add
      further support to the view that A2a-receptor agonists may be potentially useful
      antipsychotic agents.

PMID- 9172166
TI  - A beta 42 is the predominant form of amyloid beta-protein in the brains of short
      term survivors of head injury.
AB  - Fatal head injury results in the formation of diffuse parenchymal deposits of
      amyloid beta-protein (A beta) in the brains of approximately 30% of individuals.
      We used carboxyl terminal-specific antisera to examine the exact nature of these
      deposits in paraffin sections of neocortex from seven head-injured patients.
      Immunostaining for A beta 42 was observed in all parenchymal deposits whereas
      staining for A beta 40, the form of the protein which predominates in serum and
      cerebrospinal fluid, was seen in only a small proportion of deposits. The
      relative paucity of A beta 40 suggests that post-traumatic deposits do not arise
      as a result of passive leakage from damaged cerebral blood vessels but are
      similar to the early A beta 42 parenchymal deposits seen in Down's syndrome and
      Alzheimer's disease.

PMID- 9172167
TI  - Apolipoprotein E genotype in schizophrenia: frequency, age of onset, and
      neuropathologic features.
AB  - Apolipoprotein E (ApoE) genotype has been found to affect the expression of a
      variety of neuropsychiatric disorders. We determined ApoE genotype frequencies
      and their relationship to clinical and pathological features in a diverse cohort
      of individuals with schizophrenia. There were no differences in ApoE genotype
      frequencies between schizophrenics and controls. However, the ApoE epsilon 4
      genotype was associated with a younger age of onset of schizophrenia, and in an
      elderly subsample, individuals with the epsilon 4 allele more frequently
      exhibited co-existent dementia and had more neurofibrillary pathology (although
      none of the cases met criteria for Alzheimer's disease). This examination of ApoE
      in relation to clinical and neurobiological features of schizophrenia suggests
      that it modifies the phenotypic expression of the disease.

PMID- 9172168
TI  - Risk for non-insulin-dependent diabetes in the normoglycaemic elderly is
      associated with impaired cognitive function.
AB  - We studied cognitive function in normoglycaemic elderly subjects at different
      risk levels for developing non-insulin-dependent diabetes mellitus (NIDDM) and in
      patients with NIDDM. Risk for NIDDM was considered increased if both 2 h glucose
      and insulin values on oral glucose tolerance testing were higher than the median
      in normoglycaemic subjects, and low if the respective values were lower than the
      median. The increased risk group showed impairment on tests of immediate and
      delayed memory, attention, visuomotor speed and verbal fluency. Moreover, the
      increased risk group did not differ from patients with NIDDM on any cognitive
      tests. Our results suggest that increased risk for NIDDM is associated with
      widely affected cognitive function in the normoglycaemic elderly, highlighting
      the importance of healthy living habits.

PMID- 9172169
TI  - Developmental expression of 5-HT7 receptor mRNA in rat brain visual structures
      after neonatal enucleation.
AB  - Binocular enucleation is a useful experimental tool for studying mechanisms of
      neuronal plasticity. Serotonin (5-HT) is a neuromodulator that mediates a wide
      range of physiological functions by activating multiple receptors. We have
      performed an in situ hybridization study to analyse in detail the regional
      distribution of 5-HT7 receptor mRNA expression during postnatal development in
      different brain visual areas following neonatal binocular enucleation. We found
      that eye removal clearly induced 5-HT7 receptor mRNA expression in the stratum
      opticum of superior colliculus, this effect being especially evident at postnatal
      day 21 (P21). Similarly, there was a clear lesion-induced up-regulation of
      receptor mRNA expression in the primary visual cortex from P15 through P21. These
      results suggest a plastic role of 5-HT7 receptor during neurogenesis triggered by
      eye removal.

PMID- 9172170
TI  - Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's
      disease pedigrees and preliminary evidence for association of presenilin-1
      mutations with a novel phenotype.
AB  - Eleven early-onset dementia families, all with affected individuals who have
      either presented clinical symptoms of early onset familial Alzheimer's disease
      (EOFAD) or have been confirmed to have EOFAD by autopsy, and two early onset
      cases with biopsy-confirmed AD pathology, were screened for missense mutations in
      the entire coding region of presenilin-1 (PS-1) and -2 (PS-2) genes. Missense
      mutations were detected by direct sequence analysis of PCR products amplified
      from genomic DNA templates of affected individuals. Three pedigrees were
      attributable to known mutations in the PS-1 gene: P264L, E280A and the splice
      acceptor site (G to T) mutation, which results in the deletion of residues 290
      319 of PS-1 (PS-1 delta 290-319). In a fourth pedigree, a novel PS-1 mutation was
      identified in exon 7 (M233T), which is homologous to a pathogenic PS-2 mutation
      (M239V), and is characterized by a very early average age of onset (before the
      age of 35). In one early onset case, another novel PS-1 mutation was identified
      in exon 8 (R278T). Of the five remaining families and the other early onset case,
      none have missense mutations in the PS-1 or PS-2 genes, or in exon 16 and 17 of
      the APP gene. Moreover, two of the PS-1 mutations, PS-1 delta 290-319 and R278T,
      are associated with the co-presentation of familial spastic paraparesis (FSP) in
      some of the affected family members. Our data raise the possibility that the
      phenotypic spectrum associated with PS-1 mutations may extend beyond typical FAD
      to include FSP, a disease heretofore unsuspected to bear any relationship to FAD.
      In addition, our data suggest that other novel EOFAD loci, in addition to APP and
      the presenilin genes, are involved in the aetiology of up to 50% of EOFAD cases.

PMID- 9172171
TI  - Eating-associated VMN-dopamine levels of rats: comparison of oral and
      intragastric feeding.
AB  - Eating is associated with persistently low dopamine (DA) concentration in the
      ventromedial hypothalamic nucleus (VMN), postulated to influence postprandial
      satiety. Whether pregastric factors contribute to eating-associated low VMN-DA
      was examined. VMN-DA levels were continuously measured in awake rats, food
      deprived for 24 h, and either subsequently allowed to eat solid chow freely
      available for 20 min, an oral liquid diet, or an isovolemic isocaloric liquid
      diet infused intragastrically to bypass the oropharynx. Eating either solid chow
      or a liquid diet was associated with an immediate decrease in VMN-DA
      concentration. The lower VMN-DA concentration lasted longer after solid chow was
      consumed than following consumption of the liquid diet. When the oropharynx was
      bypassed no significant change in VMN-DA concentration was observed either during
      or after the liquid diet was infused. Results suggest that pregastric
      oropharyngeal factors contribute to eating-associated low VMN-DA concentration.

PMID- 9172172
TI  - The inclination of artists to partition line sections in the golden ratio.
AB  - A sample of 51 mature, established, and successful artists and sculptors were
      invited to partition line segments with a pencil mark so that the resulting two
      line segments formed the most pleasing proportion. It was anticipated that this
      particular group of subjects would choose the golden section. However, the
      proportion of 1:2 and not the golden section was the over-all ratio of choice.
      These data were contrasted with those obtained in similar but earlier work
      conducted by another researcher who tested psychology students as subjects.

PMID- 9172173
TI  - Effect of numerical representations of risk on perception.

PMID- 9172174
TI  - An examination of the relationship between accountants' scores on field
      independence and use of and attitude toward computers.
AB  - This study examined the performance of 127 accountants on the Group Embedded
      Figures Test and assessed the accountants' use of and attitude toward using
      computers to complete job-related tasks. The data support Bernardi's (1993)
      finding that there has been a shift over time in scores on field independence
      among accountants. Comparison of field-independence scores by computer use and
      attitudes support Bernardi's (1993) hypothesis of an association between the
      shift in field independence and accountant's use of and attitude toward
      computers.

PMID- 9172175
TI  - Does local or global orientation determine the McCollough effect?
AB  - In this research, the McCollough effect was observed by using an ambiguous test
      pattern of coarse gratings made out of fine gratings. Coarse gratings meet at
      right angles to fine gratings. The global features (coarse gratings) in the test
      pattern became more salient if the test pattern was blurred, and the frequency of
      the McCollough effect, corresponding to the global orientation of the test
      pattern, increased with the increase of the extent of blur. The McCollough
      effects corresponding to the local orientation of the test pattern occurred
      frequently if the subjects adapted to fine gratings before viewing the test
      pattern, whereas the McCollough effects corresponding to the global orientation
      of the test pattern occurred frequently if the subjects adapted to coarse
      gratings. Our results indicate that the perceptual organization is an important
      determinant in the McCollough effect.

PMID- 9172176
TI  - Ratings of stress by rugby referees.
AB  - 682 rugby referees from Wales, Scotland, and England rated their stress
      associated with refereeing on a 3-item scale. Mean ratings for the total sample
      and each group were between "very little" and "a moderate amount." Results
      support earlier studies, suggesting that most sport officials do not experience
      much stress while officiating.

PMID- 9172177
TI  - Lack of correlations of sense-modality-oriented indices of learning styles with
      each other and with classroom tasks.
AB  - Four indices used to measure 36 students' preferred sense modality did not
      correlate well with each other or with classroom tasks such as recalling visual
      and auditory information from a videotape, imaging ability, problem solving, etc.
      Three were paper-and-pencil indices for group presentation (Fleming and Mills'
      test, Kirby, Moore, and Schofield's index, and Westman's index), and one required
      individual testing (Swassing-Barbe Modality Index). Students indicated that their
      analyses of task requirements rather than their preferences for sense modality
      determined the use of their sense modalities.

PMID- 9172178
TI  - Perception of a border defined by rapidly reversing luminance contrast.
AB  - We report a new visual illusion of a perceptual boundary visible between two
      contiguous regions of equal luminance when the intensity is modulated with a
      temporal frequency that is higher than the critical fusion rate. Measurements of
      the luminance threshold of the perceptual border with various slopes of the
      luminance gradient yielded a function suggestive of the range of ocular
      instability. These findings raise the possibility that this new border illusion
      may be influenced by involuntary ocular motion during fixation.

PMID- 9172179
TI  - Goal confidence and difficulty as predictors of goal attainment in junior high
      school cross-country runners.
AB  - This study examined the influence of confidence in a goal and difficulty of the
      goal on the attainment of self-set goals regarding time and position. 63 junior
      high school cross-country runners (M age = 13.5 yr., SD = .5 yr.) completed a 6
      item Race Goals Questionnaire approximately 24 hr. prior to a 2-km race.
      Attainability of a goal was assessed by categorizing runners into either a
      Performed to Expectation (Time, Position) or an Underperformed group (Time,
      Position). A 2 x 2 multivariate analysis of variance indicated significant
      differences between the two groups on Time for Confidence in goals and on
      Difficulty of Goals. There were no differences between the two groups on
      Position. Discriminant function analyses to predict time goal performance
      indicated that 47 (74.6%) participants could be correctly classified into the
      groups by Time on the basis of Confidence in Goals, and Difficulty of Goals.
      Discriminant function analyses to predict performance in terms of Position
      indicated 38 participants (60.3%) could be correctly classified on the basis of
      Confidence in Goals, and Difficulty of Goals. The results concur with previous
      proposals that goals regarding time and position have a differential influence on
      performance.

PMID- 9172180
TI  - Psychology of computer use: XLIV. Computer anxiety and learning style.
AB  - The relation between scores for computer anxiety and for Kolb's Learning Style
      Inventory was investigated (N = 204). Scores on computer anxiety correlated
      negatively with scores on the Active-Reflective index. Further, those classified
      as Convergers reported lower scores on computer anxiety than did those classified
      as Divergers.

PMID- 9172181
TI  - A disability awareness unit in physical education and attitudes of elementary
      school students.
AB  - With informed consent 430 students in Grades 2 through 6 from two elementary
      schools in a large, suburban-rural school district were pretested and post-tested
      on the Children's Attitudes Toward Handicapped Scale. Students, by grade, rotated
      among four to seven different locations within the school's gymnasium, each
      identified by a different disability. There was no control group. Repeated
      measures analysis of variance was used to assess the effect of sex on pre- and
      postexperimental exposures on the attitudinal scores. A 2 x 5 (school x grade)
      analysis of variance assessed the main effects of school and grade on attitudinal
      scores. Significant effects were sex but not school or grade.

PMID- 9172182
TI  - Effectiveness of a training program with physical education students and
      experienced physical education teachers in scoring the Test of Gross Motor
      Development.
AB  - Recently there has been an increase in the need for instruction and assessment of
      motor skills of students with disabilities for the regular physical education
      teacher; however, research has indicated that training of physical educators in
      assessment of motor skills for students with disabilities is often inadequate.
      Models of teaching preparation such as the infusion approach stress the need to
      integrate teaching and assessment techniques applicable to students with and
      without disabilities. In this study, the effectiveness of assessment training on
      the accuracy of scoring the Test of Gross Motor Development was investigated. Two
      students (one special education, one nonspecial education) were filmed and
      evaluated by three experts in the field of adapted physical education. The expert
      raters' scores were then compared to scores obtained by 26 physical education
      students and 26 experienced physical education teachers. Results of the study
      indicate that the instruction received in an assessment course enables
      undergraduate physical education students to assess accurately the motor skill
      performance of students with and without disabilities.

PMID- 9172183
TI  - Illusion decrement as a function of duration of inspection and figure type.
AB  - Illusion decrement for the Muller-Lyer and Horizontal-Vertical illusions was
      examined. The experiment consisted of an initial adjustment of an illusion
      followed by 20 test trials, each with an intervening 60-sec. intertrial interval
      during which a comparator line and a standard line set to equality were visually
      inspected for 0, 20, 40, or 60 sec. After each intertrial interval the length of
      the comparator line was reset by the experimenter to either 0 or 90 cm, and
      subjects then adjusted its length to perceived equality with the standard line
      (42 cm). Illusion decrement was inversely related to the duration of inspection
      for each illusion, with significant reductions in magnitude of illusion observed
      for all groups. These results support prior demonstrations that perceptual
      learning mechanisms are operative during brief periods of visual inspection,
      especially when these periods are followed by the opportunity to make repeated
      adjustments.

PMID- 9172184
TI  - Effects of cue validity upon performance in the attention cueing paradigm.
AB  - Two experiments were run wherein normal subjects made choice reactions to targets
      preceded by location cues. Systematic manipulation of the predictive validity of
      the cue produced consistent advantages for subjects in the low as opposed to the
      high predictive validity condition. Performance advantages were observed in both
      response time and accuracy measures. The results are discussed with respect to
      models of visual orienting and controlled versus automatic processing.

PMID- 9172185
TI  - On the current status of rated perceived exertion.
AB  - This paper chronicles the psychophysical principles which led to the development
      of the Ratings of Perceived Exertion (RPE) scale by Borg in 1970 and a concise,
      comprehensive summary of research on the scale. The current status of research is
      examined by discussion of several important areas within the field including
      psychophysical scaling, scale development, psychometrics, and applications.
      Physiological and psychological approaches are examined and the need for an
      interdisciplinary approach is addressed.

PMID- 9172186
TI  - Structuring of perceived interrelations among life events for college students.
AB  - We attempted to structure a student's perceived interrelationships among major
      life events in an hierarchy by the use of the Interpretive Structural Modeling
      (ISM) method from paired-comparison data. Analysis suggested that, although the
      perception of the ages at which an individual will experience major life events
      is strongly influenced by age norm and is less variant among persons, the
      perception of the interrelationships among life events is more variant.

PMID- 9172187
TI  - Evaluation of selected life-skill modules from the contemporary health series
      with students in grade.
AB  - The purpose of the study was to assess the effects over a school term of selected
      life-skill modules from The Contemporary Health Series-Into Adolescence on scores
      for self-esteem, health (drug) attitudes, and behaviors of sixth-grade students.
      The 328 students were from classrooms assigned to either-experimental or control
      conditions. Analysis indicated that students exposed to selected modules from the
      curriculum series reported positive changes on a number of health-related
      variables in the questionnaire.

PMID- 9172188
TI  - Effects on archery performance of manipulating metamotivational state and felt
      arousal.
AB  - This study investigated the effect of the four different combinations of
      metamotivational state and felt arousal level (telic-low, paratelic-low, telic
      high, paratelic-high) on archery performance. Skilled, average, and novice
      archers (n = 28) were voluntary subjects, randomly divided into 2 groups,
      balanced for ability. Each group performed 2 out of the 4 experimental
      conditions. In this reversal theory-based field experiment, telic and paratelic
      metamotivational states and arousal level were manipulated prior to archery
      performance. The hypothesis that archery performance would be superior under
      telic-low arousal conditions was rejected, but evidence pointed to the possible
      importance of hedonic tone in performance. Post boc analysis showed differences
      between combined high (telic-low, paratelic-high) and combined low (telic-low,
      paratelic-high) hedonic-tone groups which fell short of significance. This
      observation is taken as justification for further exploration of the relationship
      between hedonic tone and sports performance.

PMID- 9172189
TI  - Noise-limited detection in young and old observers.
AB  - 11 young (M age = 24.3 yr.) and 11 old (M age = 67.4 yr.) observers attempted to
      detect signals of limited bandwidth in visual noise. The older observers did not
      perform as well as the young ones. We considered whether, as suggested by a
      current hypothesis, these differences could be attributed to higher internal
      additive noise in the elderly observers. The results suggested that internal
      noise did not differ across the two age groups and that the lower performance of
      the older observers stemmed instead from reduced processing efficiency.

PMID- 9172190
TI  - Test-retest reliability of a battery of sensory motor and physiological measures
      of aging.
AB  - We report test-retest reliabilities for a battery of tests (vision, hearing,
      vibration sense, proprioception, forced expiratory volume, blood pressure, grip
      strength, and sway) shown previously to predict functional age. Fifty women aged
      60 to 86 were retested on the battery after 3 months. All tests except
      proprioception and blood pressure had reliabilities between .70 and .94. We
      conclude that the battery provides reliable measures of sensory, motor, and
      physiological variables which may be used as markers of biological aging in
      psychological research.

PMID- 9172191
TI  - Vertical eye movements during mental tasks: a re-examination and hypothesis.
AB  - Previous research has shown that both vertical and lateral eye movements occur
      during mental tasks, although the neuropsychological basis for such movements
      remains unclear. Vertical and lateral eye movements were recorded from 24 right
      dominant subjects as they performed three different mental tasks: a mental
      arithmetic task, a visuospatial imagery task, and a proverb interpretation task.
      Significant upward biases in the direction of the initial eye movement were
      observed as subjects answered a series of arithmetic and visuospatial questions
      along with a nonsignificant upward bias following a series of proverbs that
      subjects had to interpret. By contrast, no consistent lateral eye movement biases
      were found during any task. The results are interpreted according to Previc's
      recent theory linking processing in the upper and lower visual fields to ventral
      versus dorsal posterior cortical activation, respectively.

PMID- 9172192
TI  - Michigan physicians' perceptions of their role in managing obesity.
AB  - In a random sample of 211 primary-care physicians in Michigan, about 33% (n = 70)
      perceived their role in the prevention of obesity as coordinating and 39% (n =
      82) as cooperative and of equal importance to that of other professionals.
      Perceived barriers to prevention of obesity were inadequate time to educate
      patients, method of reimbursement, and inadequate training in management of
      obesity. These results suggest that physicians' involvement in managing obesity
      can improve if they work closely with other health professionals.

PMID- 9172193
TI  - Dissociated contextual interference effects in children and adults.
AB  - 24 7-yr.-old children and 24 university-age adults practiced a ballistic aiming
      task under either low contextual interference (blocked practice) or high
      contextual interference (random practice). All subjects performed 90 acquisition
      trials, followed by 20 transfer trials and 15 retention trials. Similar to
      previous findings, the adults performed the acquisition trials better under
      blocked than under random conditions, yet performed the retention and transfer
      tests better after random than blocked practice. No differences in acquisition
      were found between blocked and random practice conditions for the children;
      nevertheless, the random group performed the retention and transfer tests better
      than the blocked group. The results are discussed in relation to applied and
      theoretical issues of contextual interference.

PMID- 9172194
TI  - Sleep characteristics of Japanese working men who score alexithymic on the
      Toronto Alexithymia Scale.
AB  - This study examined the relationship of sleep characteristics including insomnia
      with scores on alexithymia in a sample of 171 Japanese working men. Levels of
      nonrestorative sleep and daytime sleepiness reported on a sleep questionnaire
      were significantly associated with scores on Depression and Confusion on the
      Profile of Mood States for Japanese men who had a high mean score on the Toronto
      Alexithymia Scale.

PMID- 9172196
TI  - Factors associated with regular exercise.
AB  - Using a telephone survey, this study investigated participation in exercise, the
      reasons for exercising, and the role of health and fitness facilities in
      promoting regular exercise. For the sample of 450 adults living in southern New
      York State and having an annual household income of at least $50,000, in contrast
      to estimates indicating that a majority of Americans do not exercise regularly,
      results from this telephone survey indicated that 62.7% of the respondents
      engaged in regular exercise. Staying in shape was given by 34.9% of the
      respondents as their major reason. Another 31.7% reported that they exercise to
      keep healthy. Use of a health club was associated with regular exercise. A lack
      of time emerged as the major impediment to exercising regularly. Apart from the
      high percentage of regular exercisers in the sample under study, these results
      generally confirm previous research on participation in regular exercise and the
      factors supporting it.

PMID- 9172195
TI  - Fundamental gross motor skill performance by girls and boys with learning
      disabilities.
AB  - The purpose of this study was to compare the performance of fundamental gross
      motor skills by 10 girls and 10 boys, 7 yr. old, with learning disabilities.
      Their skills were assessed on the Test of Gross Motor Development. The boys
      achieved significantly higher mean scores than the girls on the subtests of
      Locomotor Skills and Object Control Skills, and on the Gross Motor Development
      Quotient.

PMID- 9172197
TI  - Interscorers' agreement of the human figure drawings with a referred group of
      children.
AB  - Agreement of two scorers using the Koppitz scoring system for emotional
      indicators on the Human Figure Drawings with 30 subjects randomly chosen from 132
      students referred for special education services was .85. Implications for
      clinicians using the Human Figure Drawings in a battery of tests are discussed.

PMID- 9172198
TI  - Cortisol responses in adults who stutter: coping preferences and apprehension
      about communication.
AB  - This study evaluated the moderating effects of individuals' coping styles for
      physiological reactivity to a stressor in the laboratory in 11 persons who
      stuttered and 11 persons who did not stutter. Reactivity was defined as changes
      in levels of salivary cortisol after a stressor. Subjects were grouped according
      to scores on apprehension about communication. Individuals scoring high on
      Communication Apprehension showed significantly elevated cortisol levels compared
      to those scoring low on Communication Apprehension. Stuttering subjects who
      scored high on Communication Apprehension and used emotion-based coping
      strategies showed the largest elevations in cortisol levels.

PMID- 9172199
TI  - Benefits of physical activity.
AB  - A survey of 44 men concerning their exercise and sport participation indicated
      the physical, emotional, and social benefits associated with being active.
      Subjects felt that employer-paid membership in a fitness club was important and
      that instructional sport classes were beneficial in improving skill.

PMID- 9172200
TI  - Accomplishments during young adulthood of children originally diagnosed with
      minimal cerebral dysfunction: a ten-year follow-up study.
AB  - To gather data about the adult accomplishments of persons diagnosed with minimal
      cerebral dysfunction this retrospective study evaluated 57 subjects at ten-year
      follow-up. Two-thirds of the subjects graduated from high school with an average
      of 11.8 years of education. Factors correlating with educational outcome included
      intelligence quotient, age at initial evaluation, and parental socioeconomic
      status. Adult accomplishments appear related to intelligence and to the presence
      of family or behavior problems.

PMID- 9172201
TI  - Sexual esteem, sexual depression, and sexual preoccupation in the exchange
      approach to sexuality.
AB  - A sample of 124 undergraduate students completed the Sexuality Scale and the
      Sexual Approach Questionnaire developed by Snell. The analysis indicated that
      those who scored high on the Exchange approach to sexuality (n = 43) scored lower
      on Sexual Esteem and higher on Sexual Depression and Sexual Preoccupation than
      those who scored low on Exchange (n = 43). Furthermore, men (n = 49) scored
      higher on preoccupation with sex than did women (n = 75).

PMID- 9172202
TI  - Sex-related coping responses in mice selectively bred for aggression.
AB  - Sex differences in strategies of coping with novel situations were studied in
      three strains of mice with regard to metabolism and open-field and maze activity
      as well as learning-induced adjustment. The 140 mice were selectively bred for
      high (Turku Aggressive [TA]) and low (Turku Nonaggressive [TNA]) levels of
      aggressiveness and originated from a Swiss albino stock normally distributed [N]
      for aggressiveness. The results indicated that TNA sex differences are more
      similar to those of the control N mice as compared to those of TA mice. In maze
      learning, however, the sex differences of TA mice are more in agreement with
      those of the N strain. Recordings of metabolism and open-field as well as maze
      activity were correlates of both gender and strain. Sex differences in learning
      induced open-field coping behavior were unrelated to strain.

PMID- 9172203
TI  - Parental representation of children during the first year of life: a longitudinal
      comparison of mothers' and fathers' responses on Semantic Differential Scales.
AB  - The aim of this paper was to investigate parental representation over time using
      a specially devised Semantic Differential Scale, developed in the context of
      longitudinal research, carried out during children's first two years of life. 42
      parent-couples, during their first experience of parenthood were asked separately
      to rate the concept of "my child" in specific periods of their child's first year
      of life. The analysis highlighted the complexity of parental representation of
      babies.

PMID- 9172204
TI  - Two scales of death anxiety: their reliability and correlation among Kuwaiti
      samples.
AB  - Arabic versions of the Templer Death Anxiety Scale and the Thorson and Powell
      Revised Death Anxiety Scale were administered to 117 male and 157 female Kuwaiti
      undergraduates. Cronbach coefficients alpha for the two scales were,
      respectively, .79 and .77. Pearson correlations for scores on the two scales were
      .54, .67, and .64 for men, women and the combined group, respectively, so
      reliability and concurrent validity of the scales were adequate for the Kuwaiti
      sample.

PMID- 9172205
TI  - Measures of language proficiency as predictors of behavioral difficulties, social
      and cognitive development in 2-year-old children.
AB  - An exploratory study of the relation of language proficiency, behavioral
      difficulties, and various areas of development was conducted with 64 children
      ranging from 24 to 29 months of age (M = 25.7 mo.). Data were obtained through
      language sampling, direct developmental assessment, and maternal reports of
      children's development and behavior. While scores on measures of expressive
      language abilities were moderately predictive of scores on measures of behavior
      problems, a stronger association was found between indices of delayed speech and
      lower scores on both social and cognitive development. The results point to the
      centrality of language development to other developmental and behavioral
      milestones. Further, findings support the importance of identifying late-talking
      children at an early age so that remedial help may be considered.

PMID- 9172206
TI  - Twins under shift work: a case study of sleep log data.
AB  - Two pairs of female twins (one pair monozygotic (MZ) and one pair dizygotic (DZ)
      attended an evening class at the same college and worked at the same factory
      under a rotating shift schedule. All the subjects agreed to keep sleep logs for
      30 days. Values for rising time were quite similar within each pair especially
      during the morning-shift schedule, while during afternoon shift and holidays,
      rising time appeared more similar in the MZ pair, but their bedtime seemed rather
      different. Morningness-Eveningness score and the amplitude of the circadian sleep
      and wakefulness (based on an autocorrelation of the data) seemed more similar in
      the MZ pair. Morningness-Eveningness score is known to be closely correlated with
      the phase position of subjects endogenous biological rhythms, e.g., body core
      temperature. Characteristics of genetic control in phase and amplitude of
      circadian rhythm measured by the above-mentioned procedure might possibly be
      detectable even under the constraints of shift-work schedule.

PMID- 9172207
TI  - Effects of pain-incompatible imagery on tolerance of pain, heart rate, and skin
      resistance.
AB  - Imagery is an important component in strategies for coping with pain. In this
      study, we examined, whether imagery influences tolerance for pain and whether
      subjects, trained in pain-incompatible imagery differ in heart rate and skin
      resistance from these in a control group during a pain-induction session. 39
      subjects were randomly assigned to two groups: imagery and control. Both groups
      had two pain-induction sessions. At intake into the study (t1). Pain Tolerance
      and Psychophysiological Reaction to Pain were assessed using a pressure
      algometer. After the first session, the experimental group received 1 hr. of
      training in pain-incompatible imagery. Seven days later, the session was repeated
      (t2). The results showed that Pain Tolerance was significantly increased in the
      group who used pain-incompatible imagery. One might follow the notion that
      increased Pain Tolerance is associated with increased Psychophysiological Pain
      Reaction, but results suggest the contrary. Subjects trained in pain-incompatible
      imagery had lower heart rates during the second pain induction than the control
      group. Groups did not differ with regard to skin resistance. It can be stated
      that besides information, cues on coping with pain may be helpful in clinical
      practice.

PMID- 9172209
TI  - Changes in scores on the Mental Rotations Test during the menstrual cycle.
AB  - The purpose of the study was to examine changes in performance on Vandenberg's
      Mental Rotations Test during the menstrual cycles of college women. Participants
      were 12 male and 34 female students recruited from undergraduate educational
      psychology and nursing classes at a large southeastern university. Each woman was
      tested once during the menstrual phase and once during the luteal phase of her
      menstrual cycle. Phases in which the testings occurred were counterbalanced. Men
      were also tested twice. For all participants, the two testing sessions were held
      exactly 14 days apart. Women who were contraceptive pill users did not perform
      significantly differently during either phase from women who were nonusers, and
      there was no interaction for pill use by phase. Therefore, users and nonusers
      were combined for a paired-sample t test which indicated that women scored
      significantly higher during the menstrual phase (Days 2-7) than during the luteal
      phase (Days 16-22 for 31 women and Days 24-26 for three women with longer
      cycles). The 12 men scored significantly higher than the 34 women during the
      initial testing; but not significantly higher than the 17 women who were in the
      menstrual phase during the first testing. Therefore, that the effect of the phase
      of menstrual cycle influences the sex difference in performance on the Mental
      Rotations Test was supported.

PMID- 9172208
TI  - Prevalence of parental substance-abuse among child psychiatric inpatients.
AB  - Of 100 consecutive admissions to an acute child psychiatric facility in South
      Africa 43 had at least one substance-abusing parent, while 10 children were from
      families in which both parents abused substances. 23 children received a
      diagnosis of depression, but no significant association was found between their
      diagnoses and parental substance-abuse status.

PMID- 9172210
TI  - Effects of nondirective suggestions on pain tolerance, pain threshold and pain
      intensity perception.
AB  - In this experiment, we followed the issue whether nondirective suggestions have
      an effect on pain threshold, pain tolerance, and perception of pain intensity. 48
      healthy subjects consented to take part. At intake into the study (t1), pain
      threshold and pain tolerance were assessed in all subjects using a pressure
      algometer. Perception of maximum pain intensity perception was rated on a scale
      of 0 to 25. Seven days later, the session was repeated (t2). Subjects were
      randomly assigned to one of two groups. One group received nondirective
      suggestions as pretreatment. Subjects listened to a tape of 20 min. which
      consisted of general information about pain theory. In this context, suggestions
      for coping with pain were placed. The other group served as a control and
      received no pretreatment. Analysis showed that pain tolerance was significantly
      prolonged in the group who received nondirective suggestions, while pain
      threshold and perception of maximum pain intensity did not differ across groups.
      This study demonstrates that nondirective suggestions are effective in prolonging
      pain tolerance. It can be stated that, beside information, cues on coping with
      pain may be helpful in clinical practice.

PMID- 9172211
TI  - Baseline respiratory sinus arrhythmia and heart-rate responses during auditory
      stimulation of children with attention-deficit hyperactivity disorder.
AB  - During passive and active listening tasks baseline respiratory sinus arrhythmia
      and heart-rate responses were studied of 18 children with Attention-Deficit
      Hyperactivity Disorder (ADHD) and 49 healthy school children. The experimental
      procedure included baseline recording (no task), a passive listening task,
      instructions, and both simple and discriminative active-listening tasks. ADHD
      subjects showed less respiratory sinus arrhythmia than normal children but were
      similarly responsive to tone stimuli.

PMID- 9172212
TI  - The blocked-random effect in pictures and words.
AB  - Picture and word recall was examined in conjunction with list organization. 60
      subjects studied a list of 30 items, either words or their pictorial equivalents.
      The 30 words/pictures, members of five conceptual categories, each represented by
      six exemplars, were presented either blocked by category or in a random order.
      While pictures were recalled better than words and a standard blocked-random
      effect was observed, the interaction indicated that the recall advantage of a
      blocked presentation was restricted to the word lists. A similar pattern emerged
      for clustering. These findings are discussed in terms of limitations upon the
      pictorial superiority effect.

PMID- 9172213
TI  - Effect of language dominance on cognitive processes in a Stroop task.
AB  - The present study investigated the effect of language dominance on 40 subjects'
      performance on a Stroop task. In the first group were 20 Education majors using
      mainly the Arabic language, while in the second group of 20 students were majors
      in English. Each group performed two different Stroop tasks. Analysis showed that
      language comprehension affected the way subjects processed the information. This
      difference was explained in terms of cognitive processes involved and by a late
      selective attention process.

PMID- 9172214
TI  - Performance time transformed by count as a determinant of difficulty in the
      Shotokan karate Heian kata set.
AB  - Black-belt subjects (10 men) were timed on each of the five Heian kata and the
      scores transformed by count. Trend analyses showed that increased performance
      time was significantly related to assumed complexity in Heian ranking.

PMID- 9172215
TI  - Sex differences on exercise dependence for men and women in a marathon road race.
AB  - Considerable research has documented a tendency towards exercise dependence among
      habitual exercisers; however, little research on possible differences in exercise
      dependence among men and women has been done. This question seems worthy of study
      given associations between exercise dependence and eating behavior problems and a
      greater incidence of eating disorders among women than men. Subjects, 18 men and
      14 women competing in a marathon road race, completed an exercise dependence
      survey developed by Hailey and Bailey in 1982. There are 14 equally weighted
      items which focus exclusively on psychological rather than physiological aspects
      of exercise dependence. Analysis of variance indicated the women reported
      significantly higher scores (3.9 +/- 1.7) than men (3.7 +/- 1.2, p < .05). While
      the design does not allow assessment of mechanisms underlying the result, one may
      express concern about the motives for participation in athletic competition.

PMID- 9172216
TI  - Multidimensional stimulus identification: instructing subjects in the order of
      reporting stimulus dimensions.
AB  - Two experiments were conducted to investigate the effects of order of report on
      identification of multidimensional stimuli under various experimental conditions.
      Statistical analysis showed that order of report affected speed of
      identification. Subjects responded faster if a natural and more appropriate way
      of reporting stimulus dimensions was used. Further, subjects reacted more slowly
      if they were free to report stimulus dimensions in any order than when they were
      forced to report in a particular order. Their performance was even worse when
      order of report was a with-in-subject factor. Response competition and response
      inhibition were proposed as possible explanations of the results. The
      implications of the results for multidimensional identification tasks are to
      designate an appropriate order of reporting stimulus dimensions and to instruct
      subjects to respond in that order.

PMID- 9172217
TI  - Slow movement as a function of advancement in the Shotokan karate kata set.

PMID- 9172218
TI  - Relationship between cognitive style and defensive style.
AB  - This study examines psychoanalytic psychology, theories of cognitive style, and
      cognitive developmental psychology to examine the relationship between cognitive
      style and defensive style. A new set of cognitive styles of visual attention is
      formulated at the following developmental levels: (1) global, (2) local, (3)
      global-plus-local at the concrete operational level, and (4) global-plus-local at
      the formal operational level, 50 subjects were administered global-local sorting
      tasks, the Sentence Preference Test, the Embedded Figures Test, and the Defense
      Style Questionnaire. Analysis provided mixed support for the hypothesized
      cognition-defense relationship. Results suggested that the "pure" character types
      are not typical and that their styles of cognition and defense are positively
      correlated, not independent as expected. However, possible measurement problems
      preclude any firm conclusions at this time.

PMID- 9172219
TI  - Comment regarding Malik, et al.'s (1996) "The method of subliminal psychodynamic
      activation: do individual thresholds make a difference?".
AB  - Researchers using the method of subliminal psychodynamic activation need to
      consider the neutrality of their control messages. Anagrams or numbers are
      recommended as even benign-sounding phrases can produce nonneutral effects.

PMID- 9172220
TI  - Variability of facilitation and inhibition as a function of cue validity and cue
      stimulus intervals in the orienting of sustained attention.
AB  - 45 subjects performed a cued vigilance task in which location cues were presented
      at intervals of 150, 350, or 550 msec. before the display of the stimulus, that
      is, three cue-stimulus intervals. Targets preceded by valid location cues led to
      a normal decrement in vigilance over time, whereas targets preceded by invalid
      location cues produced an increment in sensitivity (d'). The results suggested
      that under certain conditions shifts of attention may enhance vigilance.

PMID- 9172221
TI  - Consistency of physical therapy students' academic performance.
AB  - The consistency of physical therapy students' grades across courses was
      investigated. The grades of five entry classes were examined. Not surprisingly,
      students performed better in some courses than others. Nevertheless, considerable
      internal consistency of grades was evident within each class during the semester
      of interest. Grades in courses may reflect a common underlying construct, that
      is, academic performance of physical therapy students.

PMID- 9172222
TI  - Relevance of muscular sensitivity, muscular activity, and cognitive variables for
      pain reduction associated with EMG biofeedback in fibromyalgia.
AB  - 18 patients suffering from primary fibromyalgia received nine training sessions
      using EMG biofeedback over a period of four weeks. Pre- and posttreatment
      measurement of the baseline EMG activity of the trapezius, muscular sensitivity,
      and cognitive variables (helplessness and belief of control) were taken. Analysis
      indicated a significant reduction occurred in general intensity of pain and in
      EMG activity as well as a significant increase in muscular sensitivity. Multiple
      regression analyses indicated that the increase in muscular sensitivity
      correlated with the decrease of EMG activity in the trapezius baseline. Self
      reported pain reduction was predicted by a change in cognitive variables.

PMID- 9172223
TI  - How effective are brakes on infant walkers?
AB  - 62 children, between the ages of 9 and 18 months old, were observed in an
      instrumented walker to measure the peak horizontal pull forces. These pull forces
      were later used to evaluate an infant walker with a braking system that would
      stop on the top step of the stairs before falling down the stairs. This brake
      system is activated when part of the walker crosses over the edge of the top
      step. Using the range of horizontal pull forces generated by the 62 children, the
      horizontal brake system for walkers would not always prevent the walker from
      falling down the stairs. Four floor surfaces were compared: carpet, vinyl, glossy
      wood, and unfinished wood. The walker brake system did not always stop the
      walkers on these floor surfaces. Using the measured weights and horizontal forces
      of the 21 nonwalking children between 9 and 13 months old who represent children
      who typically fall down the stairs in a walker, a simulation procedure was
      completed to represent the worse possible force condition, the peak horizontal
      force, for each of the 21 children. During this simulation, brakes would have
      failed all the time for 18 of the 21 children, and at least half the time for the
      remaining 3 children. These brake systems may provide false security to parents
      who use these walkers, since there are no published standards regarding the
      performance of brake systems for infant walkers as a safety device.

PMID- 9172224
TI  - Assessment of functional fitness among independent older adults: a preliminary
      report.
AB  - The goal of the present study was to develop a field test for assessing various
      components of daily activities among independent older adults. The test has 8
      subtests of Coordination, Balance, Arms Strength, Upper Extremities Flexibility,
      Lower Extremities Flexibility, Agility, Legs Strength, and Walking Ability.
      Subjects were 252 volunteers whose mean age was 72.4 (+/-6.3) yr. A self-report
      daily functioning scale and a global health scale were also administered to a
      group. Analysis indicated test-retest reliability of approximately .8, and factor
      analysis yielded three factors interpretable and meaningful as domains of motor
      function, i.e., neuromuscular function, strength, and flexibility. Correlations
      of scores on the test with scores on the two self-rated scales of daily
      functioning and health, while controlling for age, were significant, suggesting
      the test measures skills that represent the main activities of daily functioning.

PMID- 9172225
TI  - Individual differences in circadian variations of consumers' emotional state.
AB  - A laboratory study investigated the effect of circadian orientation on consumers'
      emotional state at different times of day. Subjects' emotional state was measured
      using the Pleasure-Arousal-Dominance scale in the morning and in the evening.
      Individual circadian orientation (morningness-eveningness) was also assessed.
      Analyses showed that changes in consumers' emotional state as a function of the
      time of the day is moderated by individual differences in circadian orientation.
      Morning-types were in a more pleasurable emotional state in the morning than in
      the evening. The predicted reversed pattern for the evening-types did not reach
      significance. Null effects were reported for the arousal and submissive/dominance
      dimensions of emotional state. Morning-types rated themselves as more awake than
      evening-types. Morning-types were more awake in the morning than in the evening
      and vice-versa for evening-types. The magnitude of the differences between
      evening-type and morning-type individuals was significant in the morning.
      Findings are discussed from methodological, theoretical, and marketing
      perspectives.

PMID- 9172226
TI  - Role of practice and stimulus-onset-asynchrony in modulating effects of stimulus
      repetition, category relation, and response compatibility in the Eriksen flanker
      task.
AB  - In the Eriksen flanker task, irrelevant information influences reaction time
      based on three types of relationships between target and flanker, Stimulus
      Repetition, Category Relation, and Response Compatibility. The effects of
      Stimulus Repetition and Category Relation refer to the finding that reaction time
      is faster when the target and flankers are the same or belong to the same
      category, respectively. The effect of Response Compatibility refers to the
      finding that reaction time is faster when the target and flankers are assigned to
      the same response than to different responses. Two experiments were designed to
      examine whether these effects vary with practice and stimulus-onset-asynchrony.
      It was shown that the effects of Stimulus Repetition and Category Relation
      occurred only when the flankers preceded the target by 200 msec. The effect of
      Response Compatibility, however, occurred regardless of stimulus-onset
      asynchrony. Furthermore, limited practice seems necessary for the occurrence of
      response facilitation.

PMID- 9172227
TI  - Communication screening in older adults with vision loss.
AB  - 25 older adults with vision loss participated in a communication screen which
      included hearing, speech-language, and a self-assessment of communication. 64%
      failed at least two of the three screenings, suggesting that routine screening
      might identify older adults with vision loss who need rehabilitation in
      communication as a complement to visual rehabilitation.

PMID- 9172228
TI  - Interobserver agreement of perceived intelligibility of magnitude of r in
      children.
AB  - This study was designed to test whether independent listeners could correctly
      classify 162 stimuli (words) that started with a multiple trill, magnitude of r,
      followed by a vowel magnitude of a. The sounds were from 27 Spanish children
      between the ages of 3.0 and 6.6 years, pronouncing Spanish words current in their
      vocabulary. Twelve listeners were presented with the recordings of the children's
      magnitude of r production and were instructed to rate the intelligibility of the
      pronounced sound as high, medium, or low. Inter-rater agreement ranged from 85 to
      96%. Analyses of variance for each of the three production categories showed that
      there were significant differences, so it seems possible to classify the words
      starting with a trilled magnitude of r based on auditory-perceptual features into
      three broad categories according to intelligibility.

PMID- 9172229
TI  - Effects of dimenhydrinate on electroencephalographic activity.

PMID- 9172230
TI  - Effects of aging and reduced relative frequency of knowledge of results on
      learning a motor skill.
AB  - Although there is evidence for age-related changes in both cognition and motor
      control, very little is known about the effect of age on learning of new motor
      skills. The present experiment addressed the interaction between aging and the
      role of knowledge of results (KR) on a motor learning task. Using a three-segment
      task on which each segment had specific timing goals, three different
      manipulations of relative frequency of information about performance were
      compared in younger and older adults. The three conditions were (a) 100% KR in
      which information about performance on each segment was provided after every
      trial, (b) 67% KR in which the performance information was faded over trials, and
      (c) 67% KR in which the performance information was faded over the segments
      within each trial. Following 90 acquisition trials, all subjects performed
      retention, transfer, and reacquisition tests. There were age-related differences
      for movement accuracy and consistency on acquisition and on the retention tests
      but not on the transfer test. However, none of these differences interacted with
      the frequency of KR manipulations. Surprisingly, there was no effect due to the
      fading schedules of KR. In general, these results indicated that younger and
      older adults use KR in a similar way to learn a motor skill.

PMID- 9172231
TI  - Atypical chest pain in the elderly.
AB  - It has been shown that the elderly, and certain other groups, may have atypical
      clinical presentations of acute MI. It is important for the clinician to educate
      patients about the common atypical symptoms that may be experienced with an MI,
      such as dyspnea, fatigue, nausea, vomiting, and syncope. The clinician must
      always rule out acute MI in any patient who presents with these symptoms, or who
      presents with falls, sudden weakness, or worsening CHF. In order to treat
      patients aggressively and with the greatest benefit (i.e. thrombolytics or other
      reperfusion therapy), we must teach our patients and ourselves to recognize
      "silent" MIs. This will decrease the morbidity and mortality rates of acute MI in
      the elderly.

PMID- 9172232
TI  - As schools produce for primary care, training sites grow slim.

PMID- 9172233
TI  - Pharmacologic approaches to chronic pain in the older adult.
AB  - A key aspect of chronic pain management in the older adult is pharmacologic.
      Although not every elderly person has a chronic condition that leads to pain,
      these illnesses are more frequent in the later years as a consequence of the
      aging process. An understanding of physiologic changes and suggested
      pharmacologic interventions for dealing with issues related to chronic pain is
      essential. The psychosocial, cultural, and cost variables surrounding pain
      management of the older adult are also important to consider. A brief review of
      pain types and terminology precedes discussion of the key principles of pain
      management for the older adult. These principles are based on the guidelines
      published and distributed by the Agency for Health Care Policy and Research and
      the American Pain Society and are presented with a clinical focus aimed at
      improving clinician practice patterns related to pain management in the older
      adult. Concise, user-friendly medication information is presented to supplement
      the current knowledge base of practicing clinicians who prescribe analgesics and
      adjuvant medications for their patients with pain.

PMID- 9172234
TI  - Secondary amenorrhea leading to osteoporosis: incidence and prevention.
AB  - Osteoporosis is widely accepted as a "female disease" occurring primarily in
      postmenopausal women. The fact that this disease can affect premenopausal women
      experiencing menstrual dysfunction is less commonly known. Amenorrhea decreases
      bone density at an age when bone formation should still be occurring. The
      implications of this failure to attain sufficient bone density during the
      formative years are frightening. The adverse effects on skeletal strength may
      lead to devastating outcomes in this subgroup of women, either now or in the
      future. This article reviews causes, risk factors, and treatments associated with
      both osteoporosis and amenorrhea. Three causes of secondary amenorrhea are
      discussed in detail: rigorous physical training, anorexia nervosa, and use of the
      contraceptive agent medroxyprogesterone acetate injection. A review of the
      literature is presented in order to establish the link between amenorrhea and
      osteoporosis. A great many young women may be unknowingly placing themselves at
      risk for developing osteoporosis. This article includes interventions that may
      decrease this risk and improve quality of life.

PMID- 9172235
TI  - The clinical reasoning case study: a powerful teaching tool.
AB  - This article describes the limitations of typical published case studies with
      respect to their congruence with actual clinical practice and their utility in
      teaching clinical decision making to novice or student health care providers. The
      authors propose a Clinical Reasoning Case Study that closely resembles an actual
      patient encounter, yet is also a rigorous academic exercise. In which health care
      providers must think aloud as the encounter unfolds. The Clinical Reasoning Case
      Study explicates and substantiates health care providers' thought processes
      underlying each decision to collect objective and subjective data. Other unique
      characteristics of this case study include a discussion of the working diagnosis
      and the provider's relative certainty about that decision; selection of the
      single most important objective and subjective finding that led to the diagnosis;
      a chronological list of diagnostic hypotheses that were generated throughout the
      patient encounter; and an analysis of costs, including the office visit,
      diagnostic tests, medications, and treatments. The Clinical Reasoning Case Study
      is a powerful tool for teaching and evaluating the clinical reasoning process.
      Two sample case studies are provided: "A Child with a Heart Murmur" and "An
      infant with Diaper Rash."

PMID- 9172238
TI  - The importance of screening for domestic violence in all women.
AB  - Both the current and past surgeon generals of the United States and the Public
      Health objectives for Healthy People 2000 have identified family violence as an
      epidemic and have called for an organized approach to screen, treat, and prevent
      further violence. Domestic violence is not, and never has been, a "disease" of
      the poor. Thousands of women from high socioeconomic levels are beginning to
      shatter our visual image of an abused woman and are forcing us to look at current
      primary care screening practices and interventions. Domestic violence is as
      common, and in some cases more prevalent, as diseases routinely screened for such
      as breast cancer, hypothyroidism, hypertension, and colon cancer. One of the
      barriers to universal screening of domestic violence is our reliance on the
      profile of the typical battered woman. One often neglected population is women
      from higher socioeconomic groups. This article provides the rationale for
      universal screening of all women for domestic violence.

PMID- 9172239
TI  - Evaluation and management of polyneuropathy: a practical approach.
AB  - Disorders of peripheral nerves are commonly encountered by primary health care
      providers. This article reviews one of the most frequent patterns, that is,
      polyneuropathy (PN). PN is a common but complex entity. Understanding the
      pathophysiology of axons, the classification of PN, the biologic targets of
      toxins and the patterns of PN assist in the diagnosis of PN. The pathophysiology,
      symptoms, and signs are discussed along with basic steps to be taken in the
      evaluation, diagnosis, and management. Illustrative case studies are provided.
      Diagnosis may not be possible in all cases. When the etiology is unknown, ongoing
      monitoring of the polyneuropathy is emphasized, particularly in acquired
      processes where the polyneuropathy may be associated with systemic disease. In
      such instances, care of the client is directed toward symptomatic management.

PMID- 9172240
TI  - The identification and management of self-mutilating patients in primary care.
AB  - Self-mutilation has been described as a complex group of behaviors resulting in
      the deliberate destruction of body tissue without conscious suicidal intent.
      Clinical reports suggest that many adults who engage in self-destructive behavior
      have childhood histories of trauma and disrupted parental care. Painless cutting
      after a period of depersonalization, followed by relaxation and repersonalization
      after bleeding, is the typical pattern reported. Complications include social
      rejection and condemnation as a response both to the behavior or the resulting
      disfigurement. The most serious complication of self-mutilation is death as a
      direct result of damage inflicted on the body or from a drug overdose. Primary
      care providers are in an excellent position to identify and intervene in self
      injurious behavior. Establishing a trusting relationship appears to be the most
      critical component of assessing and treating the client who self-mutilates.
      Psychotherapy and psychotropic medications, though not specific to self
      mutilation, remain the most compelling treatment options.

PMID- 9172241
TI  - Sciatic pain and piriformis syndrome.
AB  - Between 70% and 80% of the population of the world experience low back pain at
      some time during their lives. A subgroup of patients who experience back pain
      also experience sciatic pain as well, with a majority of these patients seeking
      evaluation from their primary care clinician. One relatively new differential
      diagnosis to be considered when evaluating the patient with sciatica is
      piriformis syndrome. Piriformis syndrome has been documented for more than 50
      years. Yet its diagnosis still remains confusing at times. Using a case study for
      the purpose of illustration, this article outlines signs and symptoms of
      sciatica, as well as differential diagnoses to be considered when examining a
      patient with sciatica. Piriformis syndrome, diagnostic tests to be performed,
      treatment, education, and follow-up of the patient with piriformis syndrome are
      all discussed in detail. Finally, implications for primary care clinicians are
      presented.

PMID- 9172242
TI  - Zafirlukast: a new treatment for asthma.

PMID- 9172244
TI  - ERISA-HMOs are using the law against the people it was designed to protect.

PMID- 9172243
TI  - Chopart amputations.

PMID- 9172245
TI  - ACL reconstruction: semitendinosus tendon is the graft of choice.

PMID- 9172246
TI  - Anatomic endoscopic ACL reconstruction with autogenous patellar tendon graft.

PMID- 9172247
TI  - A simple method to measure compartment pressures using an intravenous catheter.
AB  - A simple method was investigated to measure compartment pressures using 16-ga
      intravenous catheters with or without side ports attached by arterial line tubing
      to a pressure transducer. Pressure measurements from the experimental catheters
      were within 4 mm Hg of the slit catheter for 99% of all readings, and pressure
      measurements from the Stryker device were within 5 mm Hg of the slit catheter for
      95% of all readings. The addition of one or two side ports to the experimental
      catheters did not alter the pressure readings. This method is comparable in
      accuracy to the slit catheter and in simplicity to the Stryker device.

PMID- 9172248
TI  - Reciprocating gait orthosis powered with electrical muscle stimulation (RGO II).
      Part II: Medical evaluation of 70 paraplegic patients.
AB  - Medical evaluation was performed on a group of paraplegics who were trained to
      walk with the Reciprocating Gait Orthosis powered with electrical muscle
      stimulation (RGO II). The evaluation included changes in spasticity, cholesterol
      level, bone metabolism, cardiac output and stroke volume, vital capacity, knee
      extensors torque, and heart rate at the end of a 30-meter walk. After an average
      of 14 weeks of training during which patients walked for 3 hours per week,
      significant reductions in spasticity, total cholesterol and low-density lipids,
      hydroxyproline/creatinine ratio, and increased knee extensor torque were evident.
      The data also showed that improvements occurred in the calcium/creatinine ratio,
      serum calcium and alkaline phosphatase levels, cardiac output and stroke volume,
      and vital capacity, yet these improvements were not statistically significant.
      The final heart rate at the end of a 30-meter walk showed that the RGO II
      required only a moderate level of exertion, which was found to be the lowest
      among the other mechanical or muscle stimulation orthoses available to
      paraplegics. It was concluded that the limited but reasonable level of functional
      regain provided by the RGO II is associated with a general improvement in the
      paraplegic's physiological condition if used for a minimum of 3 to 4 hours per
      week.

PMID- 9172249
TI  - The efficacy and safety of the hematoma block for fracture reduction in closed,
      isolated fractures.
AB  - Fracture manipulation in the emergency department often requires some method of
      anesthesia. This study evaluates the efficacy and safety of the hematoma block in
      patients with closed, isolated fractures requiring manipulative reduction. Sixty
      one patients treated with a hematoma block (HB group) prior to fracture
      manipulation were compared with 53 patients treated with either intravenous
      sedation or "conscious sedation" (NHB group). Using a pain analog scale, patients
      rated their pain from 1 (no pain) to 10 (severe pain) both prior to and during
      fracture manipulation. A pain differential score was calculated for each group.
      Results demonstrated pain differential scores of 2.7 and 0.8 for the HB and NHB
      groups, respectively. There were no complications associated with any of the
      procedures. Based on these results, we conclude that the hematoma block is an
      effective and safe method of providing anesthesia for fracture reduction in
      select patients.

PMID- 9172250
TI  - Recognizable magnetic resonance imaging characteristics of intramuscular myxoma.
AB  - Extremity intramuscular myxoma is an uncommon, deep, benign soft-tissue neoplasm.
      It is characterized clinically by slow growth and minimal symptoms. Resection
      achieving wide surgical margins is curative. This article presents the imaging
      characteristics of five extremity intramuscular myxomas. Images of this benign
      neoplasm, especially magnetic resonance imaging, are characteristic enough for
      preoperative recognition. This knowledge can facilitate treatment by avoiding
      biopsy, permitting primary myectomy, and assisting the pathologist in diagnosing
      a neoplasm that frequently has overlapping histologic characteristics with other
      soft-tissue tumors.

PMID- 9172251
TI  - Orderly oriented wire mesh: a novel porous coating.
AB  - As an alternative to commercially available porous beads and fiber metal mesh, a
      new porous coating, orderly oriented wire mesh (OOWM), was developed. Rectangular
      plugs, 10 x 5 x 5 mm with porous-coated beads, and four different OOWM
      configurations were inserted into bilateral femoral condyles of adult beagles.
      Dogs were sacrificed immediately after implantation, and at 4 weeks, 8 weeks, and
      12 weeks postimplantation. Mechanical pullout strength of plugs revealed that
      porous beads are equivalent to the simplest OOWM at 12 weeks postimplantation. Of
      the four OOWMs tested, the 25 x 25 single layer was significantly more stable
      than others at 4 weeks postimplantation. These results indicate that in an in
      vivo unloaded model, OOWM is just as effective as the porous beads in achieving
      early bone ingrowth and stability.

PMID- 9172252
TI  - Amputations of the foot and ankle: review of techniques and results.

PMID- 9172254
TI  - Metallosis mimicking infection in a cemented total knee replacement.

PMID- 9172253
TI  - Aneurysmal bone cyst involving the distal phalanx of a child.

PMID- 9172255
TI  - Bilateral hook of the hamate fractures.

PMID- 9172256
TI  - Large osteoarthritic bone cyst of the facet joint causing low back pain and
      sciatica.

PMID- 9172257
TI  - Radiologic case study. Low back pain.

PMID- 9172258
TI  - Light dosimetry in vivo.
AB  - This paper starts with definitions of radiance, fluence (rate) and other
      quantities that are important with regard to in vivo light dosimetry. The light
      distribution in mammalian tissues can be estimated from model calculations using
      measured optical properties or from direct measurements of fluence rate using a
      suitable detector. A historical introduction is therefore followed by a brief
      discussion of tissue optical properties and of calculations using diffusion
      theory, the P3-approximation or Monte Carlo simulations. In particular the form
      of the scattering function is considered in relation to the fluence rate close to
      the tissue boundary, where light is incident. Non-invasive measurements of
      optical properties yield the absorption coefficient mu a and mu s(1 - g), where
      mu s is the scattering coefficient and g is the mean cosine of the scattering
      angle. An important question is whether this combination is sufficient, or
      whether g itself must be known. It appears that for strongly forward scattering,
      as in mammalian tissues, rather detailed knowledge of the scattering function is
      needed to reliably calculate the fluence rate close to the surface. Deeper in the
      tissue mu s (1 - g) is sufficient. The construction, calibration and use of fibre
      optic probes for measurements of fluence rate in tissues or optical phantoms is
      discussed. At present, minimally invasive absolute fluence (rate) measurements
      seem to be possible with an accuracy of 10-20%. Examples are given of in vivo
      measurements in animal experiments and in humans during clinical treatments.
      Measurements in mammalian tissues, plant leaves and marine sediments are compared
      and similarities and differences pointed out. Most in vivo light fluence rate
      measurements have been concerned with photodynamic therapy (PDT): Optical
      properties of the same normal tissue may differ between patients. Tumours of the
      same histological type may even show different optical properties in a single
      patient. Treatment-induced changes of optical properties may also occur.
      Scattered light appears to contribute substantially to the light dose. All these
      phenomena emphasize the importance of in situ light measurements. Another
      important dosimetric parameter in PDT is the concentration and distribution of
      the photosensitizer. Apart from in vivo fluorescence monitoring, the
      photosensitizer part of in vivo PDT dosimetry is still in its infancy.

PMID- 9172259
TI  - Chromophores in human skin.
AB  - Human skin, especially the epidermis, contains several major solar ultraviolet
      radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid,
      amino acids, melanins and their precursors and metabolites. The lack of
      solubility of melanins prevents their absorption spectra being defined by routine
      techniques. Indirect spectroscopic methods show that their spectral properties
      depend on the stimulus for melanogenesis. The photochemical consequences of UVR
      absorption by some epidermal chromophores are relatively well understood whereas
      we lack a detailed understanding of the consequent photobiological and clinical
      responses. Skin action spectroscopy is not a reliable way of relating a
      photobiological outcome to a specific chromophore but is important for UVR hazard
      assessment. Exogenous chromophores may be administered to the skin in combination
      with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of
      sunburn and possibly skin cancer.

PMID- 9172260
TI  - Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence
      spectroscopy and elastic-scattering spectroscopy.
AB  - We review the application of fluorescence spectroscopy and elastic-scattering
      spectroscopy, over the ultraviolet-to-visible wavelength range, to minimally
      invasive medical diagnostics. The promises and hopes, as well as the
      difficulties, of these developing techniques are discussed.

PMID- 9172261
TI  - In vivo fluorescence imaging for tissue diagnostics.
AB  - Non-invasive fluorescence imaging has the potential to provide in vivo diagnostic
      information for many clinical specialties. Techniques have been developed over
      the years for simple ocular observations following UV excitation to sophisticated
      spectroscopic imaging using advanced equipment. Much of the impetus for research
      on fluorescence imaging for tissue diagnostics has come from parallel
      developments in photodynamic therapy of malignant lesions with fluorescent
      photosensitizers. However, the fluorescence of endogenous molecules (tissue
      autofluorescence) also plays an important role in most applications. In this
      paper, the possibilities of imaging tissues using fluorescence spectroscopy as a
      mean of tissue characterization are discussed. The various imaging techniques for
      extracting diagnostic information suggested in the literature are reviewed. The
      development of exogenous fluorophores for this purpose is also presented.
      Finally, the present status of clinical evaluation and future directions are
      discussed.

PMID- 9172262
TI  - Optical imaging in medicine: I. Experimental techniques.
AB  - The overwhelming scatter which occurs when optical radiation propagates through
      tissue severely limits the ability to image internal structure using measurements
      of transmitted intensity. A broad range of methods has been proposed during the
      past decade or so in order to improve imaging performance. Direct methods involve
      isolating an unscattered or least-scattered component of transmitted scattered
      light. Indirect methods generally involve measuring some characteristic of the
      temporal distribution of transmitted light, or an equivalent in the frequency
      domain, and obtaining a computational solution to the inverse problem. In this
      paper, we review the experimental techniques which have been proposed in order to
      explore both direct and indirect imaging. The relative merits and limitations of
      the various experimental methods are discussed, and we consider the future
      directions and likelihood of success of optical imaging in medicine.

PMID- 9172263
TI  - Optical imaging in medicine: II. Modelling and reconstruction.
AB  - The desire for a diagnostic optical imaging modality has motivated the
      development of image reconstruction procedures involving solution of the inverse
      problem. This approach is based on the assumption that, given a set of
      measurements of transmitted light between pairs of points on the surface of an
      object, there exists a unique three-dimensional distribution of internal
      scatterers and absorbers which would yield that set. Thus imaging becomes a task
      of solving an inverse problem using an appropriate model of photon transport. In
      this paper we examine the models that have been developed for this task, and
      review current approaches to image reconstruction. Specifically, we consider
      models based on radiative transfer theory and its derivatives, which are either
      stochastic in nature (random walk, Monte Carlo, and Markov processes) or
      deterministic (partial differential equation models and their solutions). Image
      reconstruction algorithms are discussed which are based on either direct
      backprojection, perturbation methods, nonlinear optimization, or Jacobian
      calculation. Finally we discuss some of the fundamental problems that must be
      addressed before optical tomography can be considered to be an understood
      problem, and before its full potential can be realized.

PMID- 9172264
TI  - Coherent detection techniques in optical imaging of tissues.
AB  - To form optical images from the transmitted or reflected light that is multiply
      scattered inside biological tissue, several detection techniques that extract the
      least-scattered photons or path-resolved photons have been developed. This paper
      reviews the coherent detection techniques. Emphasis is put on coherent detection
      imaging methods based on optical heterodyning, whose attractive features include
      quantum-noise-limited sensitivity, wide dynamic range, and excellent
      directionality and selectivity. Coherent detection methods have been implemented
      to achieve laser computed tomography and micrometre-resolution cross-sectional
      images in both in vivo and in vitro biological systems. Imaging works by
      ourselves and others are described, and an experimental study on coherent photon
      migration through highly scattering media is described to aid the understanding
      of the coherent detection method in selectively detecting the signal-carrying
      photons.

PMID- 9172265
TI  - Laser light delivery systems for medical applications.
AB  - For medical applications, the choice of a delivery system will be governed by the
      characteristics of the laser system on the one hand and the tissue application on
      the other. The most important parts are the beam guide and the target optics.
      Most lasers have wavelengths in the visible and near-infrared and can be
      transported by silica fibres. For the mid- and far-IR other fibre materials or
      hollow waveguides are used. At the end of the waveguide or fibre, an optically
      active component is present to direct the beam and to control the power density
      on the target tissue. The laser beam can be delivered either by focusing
      handpieces and scanning devices to treat superficial areas or through
      microscopes, endoscopes and flexible fibres to treat areas almost anywhere inside
      the human body. The characteristics of the delivery systems can be determined
      looking at beam properties, transmission and thermal properties. The delivery of
      continuous wave or pulsed laser energy, contact or non-contact, will determine
      the contribution of optical, thermal and mechanical effects to the tissue. The
      practical use of laser delivery systems is illustrated by various clinical
      applications.

PMID- 9172266
TI  - Nonlinear absorption: intraocular microsurgery and laser lithotripsy.
AB  - The paper reviews the principles of nonlinear absorption with reference to the
      present major clinical applications of plasma-mediated effects: intraocular
      microsurgery and laser lithotripsy. Emphasis is laid on the analysis of the
      working mechanisms, sources of collateral damage, and on strategies for both the
      optimization of efficacy and the minimization of side effects.

PMID- 9172267
TI  - The biology of photodynamic therapy.
AB  - The subcellular, cellular and tissue/tumour interactions with non-toxic
      photosensitizing chemicals plus non-thermal visible light (photodynamic therapy
      (PDT) are reviewed. The extent to which endothelium/vasculature is the primary
      target is discussed, and the biochemical opportunities for manipulating outcome
      highlighted. The nature of tumour destruction by PDT lends itself to imaging
      outcome by MRI and PET.

PMID- 9172268
TI  - Non-invasive determination of port wine stain anatomy and physiology for optimal
      laser treatment strategies.
AB  - The treatment of port wine stains (PWSs) using a flashlamp-pumped pulsed dye
      laser is often performed using virtually identical irradiation parameters.
      Although encouraging clinical results have been reported, we propose that lasers
      will only reach their full potential provided treatment parameters match
      individual PWS anatomy and physiology. The purpose of this paper is to review the
      progress made on the technical development and clinical implementation of (i)
      infrared tomography (IRT), optical reflectance spectroscopy (ORS) and optical low
      coherence reflectometry (OLCR) to obtain in vivo diagnostic data on individual
      PWS anatomy and physiology and (ii) models of light and heat propagation,
      predicting irreversible vascular injury in human skin, to select optimal laser
      wavelength, pulse duration, spot size and radiant exposure for complete PWS
      blanching in the fewest possible treatment sessions. Although non-invasive
      optical sensing techniques may provide significant diagnostic data, development
      of a realistic model will require a better understanding of relevant mechanisms
      for irreversible vascular injury.

PMID- 9172269
TI  - The scanning laser ophthalmoscope.
AB  - The imaging of the fundus of the eye poses two major technical challenges. First,
      it is necessary for both the illuminating and reflected beams to pass through the
      same aperture, the iris. In some commonly used instruments this leads to the use
      of levels of illumination close to the maximum tolerable by a patient. Second, in
      order to visualize the different structures present in the various layers of the
      fundus it is necessary to perform tomographic imaging. The scanning laser
      ophthalmoscope provides an answer to these particular problems. By scanning the
      fundus with a narrow laser beam most of the area of the iris is then available
      for the reflected light and so the intensity of the illuminating beam can be kept
      low, making it more acceptable for patients. The use of confocal imaging allows
      3D images to be produced. In this short review the performance of the instrument
      will be discussed and its application to a number of clinical problems in
      ophthalmology considered. Finally there will be a brief description of other
      instrumentation currently under development.

PMID- 9172270
TI  - Fibre-optic sensors in health care.
AB  - Biomedical fibre-optic sensors are attractive for the measurement of physical,
      chemical and biochemical parameters and for spectral measurements directly
      performed on the patient. An overview of fibre-optic sensors for in vivo
      monitoring is given, with particular attention paid to the advantages that these
      sensors are able to offer in different application fields such as cardiovascular
      and intensive care, angiology, gastroenterology, ophthalmology, oncology,
      neurology, dermatology and dentistry.

PMID- 9172271
TI  - Optical radiation safety of medical light sources.
AB  - The phototoxicity of medical ultraviolet (UV) sources used in dermatology has
      long been recognized. Less obvious are potential hazards to the eye and skin from
      many other optical sources-both to the patient and to the health-care worker. To
      assess potential hazards, one must consider not only the optical and radiometric
      parameters of the optical source in question but also the geometrical exposure
      factors. This knowledge is required to accurately determine the irradiances (dose
      rates) to exposed tissues. Both photochemically and thermally induced damage are
      possible from intense light sources used in medicine and surgery; however,
      thermal injury is rare unless the light source is pulsed or nearly in contact
      with tissue. Generally, photochemical interaction mechanisms are most pronounced
      at short wavelengths (UV) where photon energies are greatest, and also will be
      most readily observed for lengthy exposure durations.

PMID- 9172272
TI  - Pubertal development and onset of psychosis in childhood onset schizophrenia.
AB  - In this study, pubertal development was examined for a sample of children and
      adolescents with childhood onset schizophrenia (COS) defined as psychosis by age
      12. Developmental and psychiatric histories were obtained for 28 adolescents
      (mean age 14.5 +/- 2.3 years) with severe, treatment refractory COS (14 males, 14
      females). Age of onset of psychosis was also examined in relation to menarche and
      development of secondary sex characteristics. Girls had a trend towards
      developing secondary sex characteristics earlier than boys (P = 0.06), consistent
      with North American norms. Males (N = 14) and females (N = 14) had similar age of
      onset of psychosis. The age of development of secondary sex characteristics was
      associated with onset of psychosis for girls, but this finding was driven by one
      outlier. There was no significant correlation between development of psychosis
      and menarche. Neither male nor female probands differed significantly from their
      well siblings or from North American norms in their age of onset of pubertal
      development. There was no evidence of early onset of secondary sex
      characteristics for this sample. Finally, there was an absence of a clear
      relationship between onset of psychosis and indices of sexual development for
      these very early onset cases.

PMID- 9172273
TI  - Relationship between specific types of communication deviance and attentional
      performance in patients with schizophrenia.
AB  - Communication Deviance (CD) characterizes the speech of schizophrenic patients
      and their relatives. The relationship between specific types of CD as measured
      from verbatim transcripts of Thematic Apperception Test protocols and attentional
      performance was investigated in 27 patients with schizophrenia. Assessments were
      conducted just prior to hospital discharge. Results revealed that a continuous
      performance attentional test with visually presented stimuli was most highly
      related to the CD factor indicating that the respondent had misperceived elements
      of the card. A continuous performance attentional test with auditory stimuli was
      found to be associated with the factor reflecting odd language use in the
      speaker. A measure of selective attention/executive control, from the Stroop
      Color-Word test, was found to be most highly related to the CD factors which
      involve higher level functions such as abstraction and integration of various
      elements of the card into a coherent story. Results suggest that CD may be a
      behavioral consequence of deficits in attention and executive control, and add to
      the growing literature suggesting that specific types of neuropsychological
      deficits can be linked to specific overt behaviors.

PMID- 9172274
TI  - The Maryland Psychiatric Research Center scale and the characterization of
      involuntary movements.
AB  - The Maryland Psychiatric Research Center involuntary movement scale (MPRC scale)
      has been used in the evaluation of 1107 patients referred for drug-induced
      movement disorders. The scale has increased discrimination of body area and
      severity compared to other scales. Validity was examined using principal
      component analyses, pharmacologic response studies and associations with AIMS,
      global judgement and motor diagnosis. Reliability was examined using Cronbach's
      alpha, intraclass correlation coefficient (ICC) between raters and test-retest
      measurements. The prevalence of dyskinetic and parkinsonian signs at several
      levels of severity are reported. Total dyskinesia was strongly correlated with
      AIMS score, r = 0.97. Inter-rater reliability was 0.81-0.90 for total dyskinesia
      score. Receiver Operating Characteristic (ROC) analysis shows a total dyskinesia
      score of 4 or above to predict tardive dyskinesia, consistent with RDC-TD
      criteria. Hand dyskinesia showed a high prevalence comparable to that of oral
      dyskinesias. The MPRC scale is a valid, sensitive and reliable instrument for the
      rating of neuroleptic-induced dyskinetic and parkinsonian syndromes and may offer
      advantages over other scales in neurophysiologic research and brain imaging with
      its ease of use, uniform structure and greater discrimination of anatomic place
      and severity in the rating of involuntary movements.

PMID- 9172275
TI  - Validity of the family history method for identifying schizophrenia-related
      disorders.
AB  - We examined the family history method's validity for identifying schizophrenia
      related disorders (SRD) by comparing family history and family study derived
      diagnoses. First degree relatives (n = 284) of 48 psychiatrically disordered
      probands, predominantly with schizophrenia, were diagnosed using the Family
      History RDC (FH-RDC) which include three psychotic schizophrenia related
      disorders (P-SRD): schizophrenia, chronic SAD and chronic unspecified functional
      psychosis (CUFP). Supplementary criteria for schizophrenia related personality
      disorders (SRP), derived to identify schizotypal and paranoid personality
      disorders (PD), were also assessed. About two thirds of these relatives (n = 196;
      69.0%) were independently diagnosed by RDC and DSM-III-R on both axis I and axis
      II in a family study. The specificity was 1.0 (178/178) and the sensitivity of
      the family history derived diagnosis for P-SRD was 0.72 (13/18). Sensitivity for
      P-SRD was improved, however, by inclusion of SRP which captured three of the five
      false negative relatives. The sensitivity of SRP for schizotypal or paranoid PD
      was 0.39 (15/38) and the specificity was 0.92 (127/138). The FH-RDC have
      moderately good sensitivity and excellent specificity for the psychotic
      schizophrenia related disorders. While family history criteria for SRP are not a
      good proxy for schizotypal or paranoid PD, they can enhance the family history
      method's sensitivity for SRD.

PMID- 9172276
TI  - Comparison of MMPI profiles in medically and psychologically based insomnias.
AB  - The MMPI performance of two sub-groups of chronic insomniac patients was compared
      to determine if patients with psychologically based insomnia (Group 1) differed
      from those with medically based insomnia (Group 2). This was done to establish
      whether etiology of insomnia had an impact on the psychological picture. We
      postulated that Group 1 would show a higher overall incidence of psychopathology,
      particularly on scales suggesting internalization of distress. Surprisingly, the
      results revealed no significant differences between the groups with respect to
      these questions. When the two diagnostic groups were combined, the sample as a
      whole was characterized by a high overall prevalence of psychopathology. As many
      as 79.3% of the MMPI records contained one or more clinical scales in the
      pathological range. Depression was a prominent feature. Our findings emphasize
      the importance of not assuming that a patient with an organically-based insomnia
      (e.g. due to sleep apnea, etc.) is free of psychological disturbance. This, in
      turn, underscores the need for a psychological evaluation as a routine part of
      the diagnostic work-up of all insomniac patients, regardless of the etiology of
      their disorder.

PMID- 9172277
TI  - Depression relapse and ethological measures.
AB  - Within the framework of interactional theories on depression, the question is
      raised whether depression relapse can be predicted by observable behavior of
      remitted patients and their interviewer during an interaction (i.e. discharge
      interview). Thirty-four patients were interviewed at hospital discharge and at a
      follow-up, 6 months later. Eight patients (23.5%) had relapsed at follow-up.
      Various behaviors of patients and interviewers were observed during an interview
      by ethological methods. One of the six patient behavioral factors, and none of
      the seven interviewer factors were related to relapse. Depression relapse
      patients displayed significantly less Active Listening (intense body touching and
      head movements during listening) during the interview at hospital discharge than
      those with stable remission. Results on Active Listening could not be explained
      by the degree of retardation (HRSD) and underlined the significance of
      interpersonal mechanisms in the onset and maintenance of depression.

PMID- 9172278
TI  - Maternal wait time after questions for children with and without Down syndrome.
AB  - Maternal wait time after open- and closed-ended questions provided during
      conversation to eight children with Down syndrome (DS) and eight language-age
      (LA) matched peers was investigated. Analysis of wait time after questions that
      children did not answer indicated that a longer wait time was provided for LA
      children (M = 2.5 seconds) than for DS children (M = 1.8 seconds). These wait
      times were matched well with the children's response times when they did answer
      questions; LA children taking a mean of 1.9 seconds and DS children a mean of 1.0
      seconds to respond. Unlike DS children, LA children took significantly longer to
      respond when their answers were not topic-related to the maternal question. For
      both groups, there was no difference in wait times after closed- and open-ended
      questions and no difference for questions for which joint attention was and was
      not established.

PMID- 9172279
TI  - Changing care staff approaches to the prevention and management of aggressive
      behaviour in a residential treatment unit for persons with mental retardation and
      challenging behaviour.
AB  - The impact of a new training procedure aimed at improving staff skills in the
      preventative and reactive management of severely challenging behaviours was
      investigated within a six-place residential treatment unit. The results showed
      that there was some evidence to support the notion that the training reduced the
      number of behavioural incidents for most residents. The rates of major reactive
      strategy use (restraint and emergency medication) also declined over time, as did
      rates of staff and resident injury. Although only a limited number of these
      changes showed statistically significant correlations with time, it is argued
      that they were clinically significant when viewed against the complexity of the
      client group under study.

PMID- 9172280
TI  - Assisting older adults with severe disabilities in expressing leisure
      preferences: a protocol for determining choice-making skills.
AB  - We evaluated a protocol involving two types of choice presentations for assessing
      leisure choice-making skills of seven older adults with severe disabilities.
      Initially when presented with pairs of objects representing choices, choice
      making was validated through demonstration of an object preference. A more
      complex choice-presentation format was then employed, involving pictures to
      represent choices. If the preference identified with objects was not demonstrated
      using pictures, a replication of the object format occurred to ensure changes in
      choice making using pictures was not due to a preference change. Five
      participants demonstrated choice-making skills using objects and two demonstrated
      choices using pictures. These results reflect the importance of assessing choice
      making skills prior to presenting choice opportunities. Suggestions for future
      research focus on expanding the assessment protocol to include a wider array of
      choice-making skills and training staff to provide choices in a format
      commensurate with an individual's skill level.

PMID- 9172281
TI  - The effect of object preferences on task performance and stereotypy in a child
      with autism.
AB  - The relationship between preferred objects associated with stereotypy,
      stereotypic behavior, and accuracy of responding during a counting task by a
      child with autism was analyzed. Object preference was determined by presenting
      the child with different sets of objects and asking him to choose one. His
      choices were then rank ordered into three groups: low, medium, and high
      preference objects. Counting performance within each of the three object groups
      was then analyzed in a multi-element design, alternating preference groups.
      Teaching with high-preference objects occasioned more stereotypic behavior and
      less accurate counting than teaching with medium- and low-preference objects.
      Thus, there exists the possibility that teaching may be less successful with
      certain teaching materials, especially if those materials evoke high rates of
      incompatible behaviors.

PMID- 9172282
TI  - The differential and temporal effects of antecedent exercise on the self
      stimulatory behavior of a child with autism.
AB  - The effects of two levels of exercise (walking versus jogging) in suppressing the
      self-stimulatory behavior of a five-year-old boy with autism were examined. The
      exercise conditions were applied immediately before periods of academic
      programming. Maladaptive self-stimulatory behaviors were separately tracked,
      enabling identification of behaviors that were more susceptible to change (e.g.,
      physical self-stimulation and "out of seat" behavior) versus those that were more
      resistant (e.g., visual self-stimulation). Examination of temporal effects
      indicated a decrease in physical self-stimulation and "out of seat" behavior, but
      only for the jogging condition. In addition, sharp reductions in these behaviors
      were observed immediately following the jogging intervention and gradually
      increased but did not return to baseline levels over a 40 min period.
      Implications for further research and clinical intervention are discussed.

PMID- 9172283
TI  - Handicap-related problems in mothers of children with physical impairments.
AB  - An inventory was developed for the measurement of handicap-related problems
      experienced by mothers of children with chronic physical conditions and an
      initial evaluation of its psychometric properties was completed in a sample of
      119 mothers of children with physical or sensory impairments. Principal component
      analysis of the Handicap-related Problems for Parents Inventory (HPPI) yielded
      three subscales, which accounted for 54% of the total variance. The HPPI
      demonstrated excellent internal consistency for each scale and total score. It
      also generally had good test-retest reliability over 6-, 12-, and 18-month
      periods. There was minimal covariation between HPPI scores and demographic
      status. Concurrent validity was demonstrated by significant correlations between
      appropriate HPPI scales and measures of daily stress and the child's physical
      condition or disability status. Support for its construct validity was obtained
      when expected convergent and discriminant relationships were confirmed between
      HPPI scales and measures of maternal adaptation, maternal social support, and
      child behavior problems. Among other results, HPPI scores predicted maternal
      adaptation 18 months later. The potential uses of the HPPI in research and
      intervention with mothers of children with chronic physical conditions were
      discussed.

PMID- 9172284
TI  - Biochemical and pharmacologic rationale for the development of a synthetic
      heparin pentasaccharide.

PMID- 9172285
TI  - Antibodies to thromboplastin in systemic lupus erythematosus: isotype
      distribution and clinical significance in a series of 92 patients.
AB  - We determined the prevalence and relationship with clinical manifestations of
      antibodies to thromboplastin (aTP) in 92 patients with systemic lupus
      erythematosus (SLE). Thirty-two (35%) patients had aTP: 13 (14%) were positive
      for IgG aTP, 13 (14%) for IgM aTP, and 6 (7%) for both. Patients with aTP had an
      increased incidence of thrombosis (p = 0.01), thrombocytopenia (p < 0.001),
      hemolytic anemia (p < 0.001), and fetal losses (p = 0.03). When the IgG and IgM
      aTP isotypes were analysed separately, the IgG aTP were found to be associated
      with thrombosis (p < 0.001), thrombocytopenia (p < 0.001), and fetal losses (p =
      0.02). The IgM aTP were associated with hemolytic anemia (p < 0.001). A
      correlation was found between the titers of aTP and those of anticardiolipin
      antibodies, in both IgG (p < 0.01, r = 0.6) and IgM (p < 0.01, r = 0.64)
      isotypes, and between the titers of IgG aTP and the diluted Russell's viper venom
      time used to detect the lupus anticoagulant (p < 0.001, r = 0.42). This test is a
      reliable, reproducible and sensitive assay for the detection of antiphospholipid
      antibodies, specially in those patients under anticoagulant therapy.

PMID- 9172286
TI  - Flow cytometric analysis of coronary stent-induced alterations of platelet
      antigens in an in vitro model.
AB  - One of the limitations of coronary stenting is the subacute thrombotic occlusion.
      In an in vitro model, we examined the effects of tantalum wire stents (n = 12) on
      platelet antigens. Platelet-rich plasma (PRP) was circulated in PVC tubing
      systems. At fixed intervals over a 10-min time course, aliquots of PRP were
      drawn, stained with monoclonal antibodies (CD41a, CD42b, CD62p, and CD63), and
      analyzed by flow cytometry. Within 2 minutes of the onset of circulation,
      expression of the activation-dependent antigens CD62p and CD63 increased in all
      tubing systems with stents. This early increase was followed by a progressive
      rise in fluorescence intensity of these neoantigens over the course of 10 minutes
      (p < 0.05 vs.. control system without stent). Antigens CD41a and CD42b did not
      show significant changes in either system. The artificial surfaces and shear
      forces of stent meshes induce alterations in platelet antigens. Flow cytometry
      provides a sensitive technique for in vitro testing of the thrombogenicity of
      coronary stents, and may be useful in further improving stent biocompatibility.

PMID- 9172287
TI  - A peptide sequence from the EGF-2 like domain of FVII inhibits TF-dependent FX
      activation.
AB  - We have found that synthetic peptides derived from the two epidermal growth
      factor-like domains of factor VII are inhibitors of tissue factor dependent
      factor X activation. Inhibition was most pronounced for a constrained sequence of
      amino acids corresponding to positions 91-102 of factor VII, Cys-Val-Asn-Glu-Asn
      Gly-Gly-Cys-Glu-Gin-Tyr-Cys. The biological activity appeared to be localized to
      the tripeptide 'motif', Glu-Gln-Tyr, within the larger sequence. The cyclic
      peptide was also an inhibitor of tissue factor induced coagulation of plasma,
      using lipidated tissue factor or tissue factor expressed on the surface of living
      cells. However, it did not interfere with intrinsic coagulation. Inhibition of
      factor X activation was dose-dependent with an IC50 value of 350 microM. Kinetic
      analyses revealed non-competitive inhibition with respect to factor X and
      suggested that the peptide sequence interferes with the factor VII/tissue
      factor/factor X complex formation and function. A pentapeptide analog of the
      putative pharmacophore was also a dose-dependent inhibitor of factor X activation
      with an IC50 value of 560 microM, but the tripeptide, Glu-Gin-Tyr, alone was
      without effect. Our results suggest a direct role for the second epidermal growth
      factor-like domain of factor VII, and in particular its loop I, in the formation
      and function of the factor VII/tissue factor/factor X complex.

PMID- 9172288
TI  - A new modification of the APC resistance test.

PMID- 9172289
TI  - Association of lupus anticoagulant with transient antibodies to prothrombin in a
      patient with hypoprothrombinemia.

PMID- 9172290
TI  - Protac, a commercially available protein C activator from the venom of
      Agkistrodon contortrix contortrix, can activate factor V and factor VIII.

PMID- 9172291
TI  - Response to DDAVP stimulation in thirteen patients with Buerger's disease.

PMID- 9172292
TI  - Hemostatic markers in preterm labor.

PMID- 9172293
TI  - Hereditary diseases in dogs: working towards a common goal.

PMID- 9172294
TI  - Eradication of Aujeszky's disease virus from a Swedish pig herd using gI-/TK
      vaccine.
AB  - An attenuated glycoprotein I-negative (gI-)/thymidine kinase-negative (TK-)
      constructed vaccine was used to eradicate Aujeszky's disease virus from a large
      farrow-to-finish herd in Sweden. The herd had had problems every year for seven
      years and two attempts to eradicate the virus without vaccination had failed. At
      the start of the vaccination programme 86 per cent of the 396 breeding animals
      were seropositive to the virus. In spite of evidence of virus circulation in the
      fattening units, no fatteners were vaccinated. The breeding stock was vaccinated
      every four months and monitored serologically. Seropositive sows and boars were
      culled at an economic rate. During the programme, four breeding animals
      seroconverted to gI. Another seven animals which seroconverted to gI were
      suspected to have been infected shortly before the first test and vaccination.
      When all the seropositive breeding animals had been culled, the fattening units
      were sampled and no seropositive animals were found. The herd was declared gI
      negative 39 months after the start of the programme. Monitoring of the herd for
      another four years, until all the vaccinated animals had been culled, showed that
      the herd remained free from Aujeszky's disease virus.

PMID- 9172295
TI  - Repeated oestrus synchrony and fixed-time artificial insemination in beef cows.
AB  - The feasibility of breeding spring-calving, single-suckled beef cows without the
      use of natural service was investigated over two breeding seasons by using
      repeated oestrus synchrony and fixed-time artificial insemination (AI).
      Initially, cows were oestrus-synchronised with subcutaneous norgestomet implants
      inserted for 10 days, with an injection of prostaglandin before the implants were
      removed. The cows were inseminated once 56 hours after the implants were removed,
      and 12 days later they were re-treated with norgestomet implants to allow a
      second synchronised service. Twenty-one days after the first synchronised AI,
      milk samples were taken for progesterone assay and the norgestomet implants were
      removed. The cows received a second service 56 hours later if the 21-day milk
      progesterone assay suggested that they were not pregnant. All the cows receiving
      a second service were retreated with norgestomet implants to allow a third
      synchronised service as necessary. Pregnancy was later confirmed by rectal
      palpation. In the first year, 48 cows entered the programme and the pregnancy
      rates to the first, second and third synchronised services were 56, 69 and 40 per
      cent, respectively, with 17 per cent of cows barren at the end of the breeding
      period. In the second year, 69 cows entered the programme and the pregnancy rates
      were 58, 48 and 33 per cent to the successive services with 20 per cent of cows
      barren at the end of the breeding period. The accuracy of milk progesterone assay
      for pregnancy diagnosis was 84 per cent and 87 per cent in the first and second
      years, respectively.

PMID- 9172296
TI  - Evaluation of the effects of nursery depopulation of the profitability of 34 pig
      farms.
AB  - The financial impact of nursery depopulation was assessed on 34 pig farms by
      constructing a partial budget model to measure the profitability of the nursery
      production. The model measured margin over variable cost and used production data
      generated from a previous study; it assumed that fixed costs remained constant
      throughout the study and that feed cost, weaned pig cost and market price per
      nursery pig also remained fixed. The mean margin over variable cost per sow on
      the 34 farm after nursery depopulation was Pounds 116. Thirty-two of the farms
      showed reductions in this cost, ranging from Pounds 20 to Pounds 408 per sow, in
      the 12 months after nursery depopulation compared with the previous 12 months. Of
      the two farms which did not show an increase in profitability, one showed no
      change and the other showed a net loss of Pounds 8 per sow. The sows' serostatus
      for porcine reproductive and respiratory syndrome virus infection was monitored
      but there was no significant difference between the margin over variable cost per
      sow of the seropositive (Pounds 130) and seronegative (Pounds 170) herds.

PMID- 9172297
TI  - Age-related disease in recurrent outbreak of phocid herpesvirus type-1 infections
      in a seal rehabilitation centre: evaluation of diagnostic methods.
AB  - The prevalence and clinical signs of phocid herpesvirus type-1 (PhHV-1)
      infections among harbour seals (Phoca vitulina) in a seal rehabilitation centre
      in the Netherlands were monitored between June and September 1993 and 1994 when
      34 and 36 seals, respectively, were rehabilitated. In both years PhHV-1-related
      disease outbreaks occurred in the pupping season. PhHV-1 infections were
      diagnosed by the demonstration of a more than four-fold increase in virus
      neutralising serum antibodies in paired serum samples, by the isolation of the
      virus from swab samples in primary seal kidney cells, and by the detection of
      PhHV-1 DNA with a polymerase chain reaction (PCR) assay in swab samples. This
      assay targets a 290 bp fragment of the glycoprotein D (gD) gene equivalent of
      PhHV-1. The PCR assay when combined with Southern blotting (PCR-SB) was
      approximately 1000 times more sensitive than virus isolation when tested with
      serially diluted samples from PhHV-1-infected cell cultures. In contrast with
      virus isolation, the PCR-SB scored as positive all the animals with serological
      evidence of PhHV-1 infection. The majority of seals present in the centre during
      the outbreaks contracted the infection and developed benign upper respiratory
      disease. However, the severity of PhHV-1-related disease was inversely correlated
      with age and fatal generalised infections occurred only in neonates.

PMID- 9172298
TI  - Multicentric schwannomas causing chronic ruminal tympany and forelimb paresis in
      a Holstein cow.
AB  - A nine-year-old Holstein cow that developed recurrent ruminal tympany and an
      abnormal forelimb gait and posture ultimately became recumbent and unable to
      rise, and was euthanased. A postmortem examination demonstrated numerous
      schwannomas affecting peripheral nerves and several thoracic and abdominal
      viscera.

PMID- 9172299
TI  - Influence of breed-related factors on the course of classical swine fever virus
      infection.

PMID- 9172300
TI  - Haematoma of the heel as a cause of lameness in dairy cattle.

PMID- 9172301
TI  - PTFE toxicity in birds.

PMID- 9172302
TI  - Treatment for Haemobartonella felis in cats.

PMID- 9172303
TI  - Dental disease in chinchillas.

PMID- 9172304
TI  - Classification of the southern African sanga and east African shorthorned zebu.
AB  - Humped African cattle, which are differentiated into zebu and sanga types, have
      traditionally been classified as Bos indicus. This paper discusses existing
      evidence and presents new evidence supporting the classification of southern
      African sangas as Bos taurus and East African zebus as 'taurindicus'.
      Classification is based on karyotype, frequencies of DNA markers and protein
      polymorphisms. The Boran, an East African zebu, has an acrocentric Y chromosome
      typical of Bos indicus. The southern African sanga breeds have a submetacentric Y
      chromosome typical of Bos taurus. Frequencies of four DNA markers support the
      hypothesis that the Tuli, a southern African sanga, had taurine ancestors and the
      Boran had both taurine and indicine ancestors. Frequencies for several protein
      polymorphisms strongly suggest that southern African sangas have more in common
      with taurine than with indicine breeds, while East African zebus are an admixture
      of African taurine and Asian indicine breeds.

PMID- 9172306
TI  - Relationship of growth hormone and insulin-like growth factor-1 genotypes with
      growth and carcass traits in swine.
AB  - The contribution of chromosomal regions linked to growth hormone (GH) and insulin
      like growth factor-1 (IGF-1) loci to variation in preweaning average daily gain,
      postweaning average daily gain (ADG), 10th rib backfat, loin-eye area and muscle
      pH were evaluated. Offspring of four purebred sires (A-D; n = 150, 195, 148 and
      136, respectively) and two cross-bred sires (E and F; n = 157 and 145,
      respectively) were genotyped initially with GH and IGF-1 markers. When results of
      single marker analysis suggested possible linkage with a quantitative trait locus
      (QTL), additional flanking markers were typed for the family and interval mapping
      was performed. Growth hormone genotype was not associated with the traits
      evaluated in the study. Evidence suggestive of linkage was found for IGF-1
      genotype and ADG in one sire family (lod = 2.3) where differences were 0.032 +/-
      0.01 kg/day for alternative sire alleles. Evidence for a putative ADG QTL was
      greatest in the interval between IGF-1 and Sw1071. A similar genomic region has
      been associated with growth variation in mice; however, QTL mapping precision in
      the current study is insufficient to establish similarity.

PMID- 9172305
TI  - Chromosomal assignment of six muscle-specific genes in cattle.
AB  - Six genes expressed in skeletal or smooth muscle were assigned to bovine
      chromosomes using rodent, human or bovine cDNA probes. Myogenic determination
      factor (MYOD1) was 100% concordant with Bos taurus chromosome (BTA) 15, and
      myogenin (MYOG) was 95% concordant with BTA 16. Smooth muscle caldesmon (CALD1)
      and the skeletal muscle chloride channel gene (CLCN1) were 100% concordant with
      BTA 4. Myogenic factor 5 (MYF5) was 90% concordant with BTA 5; this assignment
      was confirmed by fluorescence in situ hybridization of a bovine genomic MYF5
      probe to BTA 5 band 13 and the homologous band on river buffalo 4q. In some
      metaphases, specific hybridization signals were also observed on BTA 15 band 23,
      and the equivalent river buffalo homologue, with the MYF5 genomic probe. Because
      MYOD1 and MYF5 share both nucleotide and functional homology and because MYOD1
      was mapped in somatic cell hybrids to BTA 15, we suggest that MYOD1 may be
      located at BTA 15 band 23. Herculin/myogenic factor 6 (MYF6) was assigned
      indirectly to BTA 5 by the hybridization of MYF5 and MYF6 probes to the same
      HindIII fragment in bovine genomic DNA. The assignment of MYF6 to BTA 5 is
      consistent with the tandem arrangement of MYF5 and MYF6 in human, mouse and
      chicken, where these tightly linked genes are separated by < 6.5 kb of DNA.

PMID- 9172307
TI  - Contribution to the physically anchored linkage map of the pig.
AB  - Thirty-three microsatellites have been mapped on the PiGMaP porcine genetic map.
      By comparison with the previously published PiGMaP maps, the maps of chromosome 2
      (140 cM/70 cM) and chromosome 3 (180 cM/110 cM) were extended and new markers
      were mapped on the p-arm extremity of chromosome 7 and on the centromeric
      extremity of chromosome 15. New orders are proposed for markers on chromosomes 3
      and 17. Six microsatellites isolated from cosmids were also localized on the
      cytogenetic map by fluorescent in situ hybridization. We tested the subcloning
      ligation mixture-polymerase chain reaction (SLiM-PCR) method for isolating
      microsatellites from cosmids. Subcloning is more effective when the cosmid
      harbours several microsatellites whereas SLiM-PCR is more straightforward when
      the cosmid contains a single microsatellite. Fifteen anonymous microsatellites
      were regionally assigned by using a hybrid cell panel. For map integration, the
      determination of a regional assignment of anonymous microsatellites by using a
      hybrid cell panel offers an alternative to microsatellite isolation from cosmids
      and their localizations by in situ hybridization.

PMID- 9172308
TI  - Genetic diversity of Asian water buffalo (Bubalus bubalis): microsatellite
      variation and a comparison with protein-coding loci.
AB  - Twenty-one microsatellite loci in 11 populations of Asian water buffalo (eight
      swamp, three river type) were analysed and, within and among populations, genetic
      variability was compared with results from 25 polymorphic protein-coding loci.
      Within-population mean heterozygosity ranged from 0.380-0.615, approximately
      twice that estimated from the protein-coding loci (0.184-0.346). Only eight
      significant departures from Hardy-Weinberg equilibrium (involving four loci) were
      detected; global tests showed significant heterozygote deficiencies for these
      four loci. Non-amplifying alleles are likely to be segregating in some or all
      populations for one of these loci, and probably for the other three. There was
      significant differentiation between the swamp and river types of water buffalo,
      and among populations within each buffalo type. Estimates of theta (measure of
      population differentiation) for each locus for the eight swamp populations were
      all highly significant (mean theta = 0.168 +/- 0.018). Mean theta for protein
      coding loci was not significantly different (0.182 +/- 0.041). The variance among
      protein-coding loci was significantly higher than among microsatellite loci,
      suggesting balancing selection affecting allele frequencies at some protein
      coding loci. Genetic distances show clear separation of the swamp and river
      types, which were estimated to have diverged at least 10,000-15,000 years ago.
      The topology of the swamp populations' microsatellite tree is consistent with
      their geographical distribution and their presumed spread through south-east
      Asia. By contrast, the tree based on the protein-coding loci distances is quite
      different, being clearly distorted by a bottleneck effect in one population, and
      possibly in at least two others. As many domestic livestock breeds are possibly
      descended from small numbers of founders, microsatellite-based trees are to be
      preferred in assessing breed genetic relationships.

PMID- 9172309
TI  - DNA polymorphisms in the chicken growth hormone gene: response to selection for
      disease resistance and association with egg production.
AB  - Analysis of the growth hormone (GH) gene in 12 strains of White Leghorn chickens
      revealed restriction fragment length polymorphisms (RFLPs) at three MspI sites
      and at a SacI site. Based on linkage disequilibrium analysis, they gave rise to
      eight different alleles (i.e. combinations of RFLPs), with five occurring at
      frequencies above 5% in at least one strain. Pairs of GH-RFLPs were at near
      maximal linkage disequilibrium, suggesting either a lack of recombination or the
      presence of selection pressure during evolution of the GH gene. Allele
      frequencies were determined in 12 non-inbred strains derived from three different
      genetic bases. These strains had been selected either for an array of egg
      production traits, resistance to Marek's disease or resistance to avian leukosis.
      Selection for disease resistance was consistently correlated with an increase in
      the frequency of one of the alleles. One strain segregated for only two alleles,
      which differed by three RFLPs. Analysis of variance in this strain indicated that
      the GH allele co-selected with resistance was associated with a delayed onset of
      ovulation but a higher persistency of ovulation as age progressed, resulting in
      an overall increase of egg production by 15% (age at first egg to 497 days). The
      resistance-associated GH allele was dominant for the onset of ovulation and
      recessive for the persistency of egg production. There was no significant effect
      of the GH genotype on juvenile body weight, egg weight or egg specific gravity.

PMID- 9172310
TI  - Associations of GH gene variants with performance traits in F2 generations of
      European wild boar, Pietrain and Meishan pigs.
AB  - The role of the porcine GH gene was investigated in 292 F2 animals of mating Wild
      Boar x Pietrain and in 310 F2 animals of mating Meishan x Pietrain. Forty-three
      traits of fattening, carcass composition, meat quality and stress resistance were
      recorded. For the analysis of associations between GH gene variants and
      quantitative traits, two restriction fragment length polymorphisms were examined.
      In the Meishan x Pietrain family eight traits related to fatness were
      significantly associated with GH genotypes, while in the Wild Boar x Pietrain
      family no significant associations were found. In the Meishan x Pietrain cross,
      the GH locus explained 11.7% to 17.7% of the total phenotypic variance in the F2
      population. The possibility of multiple alleles at the GH locus is discussed.
      Based on these results, we conclude that the GH locus should be further
      investigated in commercial breeds to determine its suitability for use in marker
      assisted selection programmes.

PMID- 9172311
TI  - Ovine-specific Y-chromosome RAPD-SCAR marker for embryo sexing.
AB  - An accurate, sensitive, and quick (approximately 3 h) method for determining the
      sex of ovine embryos was developed using polymerase chain reaction (PCR) primers
      derived from an ovine-specific Y-chromosome random amplified polymorphic DNA
      marker (UcdO43). The accuracy and sensitivity of the assay were first tested
      using genomic DNA from 10 males and 10 females of five different sheep breeds,
      and then tested using serial dilutions of male-in-female DNA. The assay was 100%
      accurate in confirming the sex of the individuals and the ovine male-specific
      fragment was detected in dilutions containing as little as 10 pg of male DNA in
      50 ng of female DNA. The assay was also confirmed to be specific for the ovine Y
      chromosome as bovine, caprine, porcine, murine, and human DNA did not amplify.
      The ovine embryo sexing method is a duplex PCR system that also includes ZFY/ZFX
      primers. ZFY/ZFX provide an internal positive control for amplification as well
      as a means to confirm the results obtained with the UcdO43 primers. All embryo
      sexing results (36/36) from our method were in agreement with the ZFY/ZFX assay
      results. However, while our method requires an internal control to detect PCR
      failure, it has the advantages of not requiring nested PCR or restriction
      endonuclease digestion of the PCR product, and concerns about cross-species
      contamination are eliminated.

PMID- 9172312
TI  - Characterization of CR1 repeat random PCR markers for mapping the chicken genome.
AB  - Polymerase chain reaction (PCR) primers complementary to portions of the chicken
      repetitive element CR1 have been used previously to generate useful markers on
      the chicken genome linkage map. To understand better the genetic basis for this
      technique and to convert CR1-PCR loci to markers useful in physical genome
      mapping, five polymorphic CR1-PCR-generated DNAs were cloned and partially
      sequenced. Inverse PCR was then employed to clone the corresponding region of the
      genomes of both the Jungle Fowl (JF) and White Leghorn (WL) parental DNA
      templates. Our results demonstrate that some of the CR1-PCR-generated DNAs arise
      from priming at an endogenous CR1 element, whereas others are due to chance
      complementarity between the CR1-PCR primer in use and random annealing sites in
      the genome, unrelated to a demonstrable CR1 element. In all five instances, it
      was possible to identify the sequence difference between the JF and WL parental
      DNAs that gave rise to the initial polymorphism and design allele-specific PCR
      primer sets that uniquely detect that polymorphism. In four of the five
      instances, the polymorphism was a one or two basepair sequence difference within
      the primer annealing site, but in the fifth case the responsible difference was
      outside, but very close to, the annealing site. In all instances the allele
      specific PCR for the sequence polymorphism mapped identically with the
      corresponding CR1-PCR amplification polymorphism. We conclude that CR1-PCR
      provides an efficient and reliable mechanism for genome mapping in avians that
      can correlate linkage and physical mapping approaches.

PMID- 9172313
TI  - Assignment of the casein kinase II gene family to cattle chromosomes.
AB  - Theileriosis, or East Coast fever, a parasitic disease in cattle, is associated
      with overexpression of casein kinase II. Casein kinase II is composed of two
      catalytic subunits (alpha or alpha') and two regulatory beta subunits. The genes
      encoding these subunits of casein kinase II were mapped to bovine chromosomes by
      polymerase chain reaction analysis of a well-characterized bovine x rodent
      somatic hybrid cell panel. The alpha-subunit (CSNK2A1) was mapped to bovine
      chromosome 13, the alpha'-subunit (CSNK2A2) to chromosome 5 and the beta-subunit
      (CSNK2B) to chromosome 23. Both CSNK2A1 and CSNK2B mapped to known regions of
      conserved synteny between human and cattle, while CSNK2A2 defined a new homology
      segment between the human and bovine genomes.

PMID- 9172314
TI  - A SINE-associated polymorphism at the bovine retinol binding protein 3 gene.

PMID- 9172315
TI  - A three-allele PstI RFLP at the porcine glucocorticoid receptor (GRL) gene.

PMID- 9172316
TI  - PvuII RFLPs at SLA class II loci: DQA and DRA.

PMID- 9172317
TI  - RFLPs at the porcine growth hormone releasing hormone (GHRH) gene.

PMID- 9172318
TI  - A DraI RFLP at the porcine insulin-like growth factor binding protein 3 (IGFBP3)
      gene.

PMID- 9172320
TI  - PZ103: a polymorphic bovine microsatellite.

PMID- 9172319
TI  - Eight canine microsatellites.

PMID- 9172321
TI  - Identification of carriers of the Welsh CASA1 variant using an allele-specific
      PCR method.

PMID- 9172322
TI  - Two SSCP alleles detected in the 5'-flanking region of bovine IGF1 gene.

PMID- 9172323
TI  - Sex-specific PCR/RFLPs in the canine ZFY/ZFX loci.

PMID- 9172324
TI  - Assignment of the canine microsatellite CanBern1 to canine chromosome 13q21.

PMID- 9172325
TI  - Five bovine microsatellite markers derived from a bovine cosmid library: CSKB067,
      CSKB068, CSKB071, CSKB072 and CSKB074.

PMID- 9172326
TI  - Molecular cloning and analysis of the ptsHI operon in Lactobacillus sake.
AB  - The ptsH and ptsI genes of Lactobacillus sake, encoding the general enzymes of
      the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS), were
      cloned and sequenced. HPr (88 amino acids), encoded by ptsH, and enzyme I (574
      amino acids), encoded by ptsI, are homologous to the corresponding known enzymes
      of other bacteria. Nucleotide sequence and mRNA analysis showed that the two
      genes are cotranscribed in a large transcript encoding both HPr and enzyme I. The
      transcription of ptsHI was shown to be independent of the carbon source. Four
      ptsI mutants were constructed by single-crossover recombination. For all mutants,
      growth on PTS carbohydrates was abolished. Surprisingly, the growth rates of
      mutants on ribose and arabinose, two carbohydrates which are not transported by
      the PTS, were accelerated. This unexpected phenotype suggests that the PTS
      negatively controls ribose and arabinose utilization in L. sake by a mechanism
      different from the regulation involving HPr described for other gram-positive
      bacteria.

PMID- 9172327
TI  - Single-crossover integration in the Lactobacillus sake chromosome and insertional
      inactivation of the ptsI and lacL genes.
AB  - Single-crossover homologous integration in Lactobacillus sake was studied.
      Integration was conducted with nonreplicative delivery vector pRV300. This vector
      is composed of a pBluescript SK- replicon for propagation in Escherichia coli and
      an erythromycin resistance marker. Random chromosomal DNA fragments of L. sake
      23K ranging between 0.3 and 3.4 kb were inserted into pRV300. The resulting
      plasmids were able to integrate into the chromosome by homologous recombination
      as single copies and were maintained stably. The single cross-over integration
      frequency was logarithmically proportional to the extent of homology between 0.3
      and 1.2 kb and reached a maximum value of 1.4 x 10(3) integrants/micrograms of
      DNA. We used this integration strategy to inactivate the ptsI gene, encoding
      enzyme I of the phosphoenolpyruvate:carbohydrate phosphotransferase system, and
      the lacL gene, which is one of the two genes required for the synthesis of a
      functional beta-galactosidase. The results indicated that our method facilitates
      genetic analysis of L. sake.

PMID- 9172328
TI  - The effects of adding lactococcal proteinase on the growth rate of Lactococcus
      lactis in milk depend on the type of enzyme.
AB  - Increasing the proteolytic activity of Lactococcus lactis cultures in milk by
      adding the corresponding proteinase resulted in a stimulation of the growth rate
      regardless of the strain and the type of proteinase, demonstrating that the rate
      of casein degradation was responsible for the growth rate limitation of L. lactis
      in milk. However, the stimulation was only transient, and the reduction in growth
      rate in the poststimulation phase depended on the type of cell envelope
      proteinase. When a PI-type proteinase was added, three causes were involved in
      the subsequent reduction in growth rate: degradation of the added proteinase,
      repression of the proteolytic activity expressed by the cells, and competition
      for peptide uptake. When a PIII-type proteinase was added, the cessation of
      stimulation was due to the autoproteolysis of the added enzyme only.

PMID- 9172329
TI  - Interaction between proteolytic strains of Lactococcus lactis influenced by
      different types of proteinase during growth in milk.
AB  - The influence of the type of cell envelope-located proteinase (PI versus PIII) on
      the associative growth of Lactococcus lactis in milk was studied. Two genetically
      engineered strains, differing only by the type of proteinase, were first used as
      a model study. An interaction occurred during the second exponential growth phase
      of the mixed culture and resulted in a decrease in growth rate of the PI-type
      proteinase strain, whereas that of the PIII-type proteinase strain remained
      unaffected. The reduction in proteolytic activity of the PI-type proteinase
      strain (presumably resulting from an inhibition of the synthesis of the enzyme)
      due to the peptides released by the PIII-type proteinase was found to be partly
      responsible for this interaction. Extension of the study to wild-type proteinase
      positive L. lactis strains showed a systematic imbalance of the mixture of the
      two strains in favor of the PIII-type proteinase strain.

PMID- 9172330
TI  - In situ analysis of denitrifying toluene- and m-xylene-degrading bacteria in a
      diesel fuel-contaminated laboratory aquifer column.
AB  - A diesel fuel-contaminated aquifer was bioremediated in situ by the injection of
      oxidants (O2 and NO3-) and nutrients in order to stimulate microbial activity.
      After 3.5 years of remediation, an aquifer sample was excavated and the material
      was used (i) to isolate bacterial strains able to grow on selected hydrocarbons
      under denitrifying conditions and (ii) to construct a laboratory aquifer column
      in order to simulate the aerobic and denitrifying remediation processes. Five
      bacterial strains isolated from the aquifer sample were able to grow on toluene
      (strains T2 to T4, T6, and T10), and nine bacterial strains grew on toluene and m
      xylene (strains M3 to M7 and M9 to M12). Strains T2 to T4, T6, and T10 were
      cocci, and strains M3 to M7 and M9 to M12 were rods. The morphological and
      physiological differences were also reflected in small sequence variabilities in
      domain III of the 23S rRNA and in the 16S rRNA. Comparative sequence analyses of
      the 16S rRNA of one isolate (T3 and M3) of each group revealed a close
      phylogenetic relationship for both groups of isolates to organisms of the genus
      Azoarcus. Two 16S rRNA-targeted oligonucleotide probes (Azo644 and Azo1251)
      targeting the experimental isolates, bacteria of the Azoarcus tolulyticus group,
      and Azoarcus evansii were used to investigate the significance of hydrocarbon
      degrading Azoarcus spp. in the laboratory aquifer column. The number of bacteria
      in the column determined after DAPI (4',6-diamidino-2-phenylindole) staining was
      5.8 x 10(8) to 1.1 x 10(9) cells g of aquifer material-1. About 1% (in the
      anaerobic zone of the column) to 2% (in the aerobic zone of the column) of these
      bacteria were detectable by using a combination of probes Azo644 and Azo1251,
      demonstrating that hydrocarbon-degrading Azoarcus spp. are significant members of
      the indigenous microbiota. More than 90% of the total number of bacteria were
      detectable by using probes targeting higher phylogenetic groups. Approximately
      80% of these bacteria belonged to the beta subdivision of the class
      Proteobacteria (beta-Proteobacteria), and 10 to 16% belonged to the gamma
      Proteobacteria. Bacteria of the alpha-Proteobacteria were present in high numbers
      (10%) only in the aerobic zone of the column.

PMID- 9172331
TI  - Detection of Coxiella burnetii in cow's milk by PCR-enzyme-linked immunosorbent
      assay combined with a novel sample preparation method.
AB  - The use of an adequate concentration of Triton X-100 enhanced immunomagnetic
      separation of Coxiella burnetii from milk. PCR-enzyme-linked immunosorbent assay
      (PCR-ELISA) could detect coxiellas more sensitively than could conventional PCR.
      PCR-ELISA is therefore thought to be suitable for the simultaneous assay of a
      large number of samples. However, the number of cows from which raw milk tested
      positive for coxiellas by PCR-ELISA was inconsistent with that found with the
      antibody to coxiella by indirect immunofluorescence assay. The inconsistency is
      thought to be associated with the differences in the infectious route, infectious
      dose, or the timing of yielding the antibody and the period of duration of the
      antibody.

PMID- 9172333
TI  - Activity of H(+)-ATPase in ruminal bacteria with special reference to acid
      tolerance.
AB  - Batch culture experiments showed that permeabilized cells and membranes of
      Ruminococcus albus and Fibrobacter succinogenes, acid-intolerant celluloytic
      bacteria, have only one-fourth to one-fifth as much H(+)-ATPase as Megasphaera
      elsdenii and Streptococcus bovis, which are relatively acid tolerant. Even in the
      cells grown in continuous culture at pH 7.0, the acid-intolerant bacteria
      contained less than half as much H(+)-ATPase as the acid-tolerant bacteria. The
      amounts of H(+)-ATPase in the acid-tolerant bacteria were increased by more than
      twofold when the cells were grown at the lowest pH permitting growth, whereas
      little increase was observed in the case of the acid-intolerant bacteria. These
      results indicate that the acid-intolerant bacteria not only contain smaller
      amounts of H(+)-ATPase at neutral pH but also have a lower capacity to enhance
      the level of H(+)-ATPase in response to low pH than the acid-tolerant bacteria.
      In addition, the H(+)-ATPases of the acid-intolerant bacteria were more sensitive
      to low pH than those of the acid-tolerant bacteria, although the optimal pHs were
      similar.

PMID- 9172332
TI  - Four genes from Pseudomonas fluorescens that encode the biosynthesis of
      pyrrolnitrin.
AB  - Pyrrolnitrin is a secondary metabolite of Pseudomonas and Burkholderia sp.
      strains with strong antifungal activity. Production of pyrrolnitrin has been
      correlated with the ability of some bacteria to control plant diseases caused by
      fungal pathogens, including the damping-off pathogen Rhizoctonia solani.
      Pseudomonas fluorescens BL915 has been reported to produce pyrrolnitrin and to be
      an effective biocontrol agent for this pathogen. We have isolated a 32-kb genomic
      DNA fragment from this strain that contains genes involved in the biosynthesis of
      pyrrolnitrin. Marker-exchange mutagenesis of this DNA with Tn5 revealed the
      presence of a 6.2-kb region that contains genes required for the synthesis of
      pyrrolnitrin. The nucleotide sequence of the 6.2-kb region was determined and
      found to contain a cluster of four genes that are required for the production of
      pyrrolnitrin. Deletion mutations in any of the four genes resulted in a
      pyrrolnitrin-nonproducing phenotype. The putative coding sequences of the four
      individual genes were cloned by PCR and fused to the tac promoter from
      Escherichia coli. In each case, the appropriate tac promoter-pyrrolnitrin gene
      fusion was shown to complement the pyrrolnitrin-negative phenotype of the
      corresponding deletion mutant. Transfer of the four gene cluster to E. coli
      resulted in the production of pyrrolnitrin by this organism, thereby
      demonstrating that the four genes are sufficient for the production of this
      metabolite and represent all of the genes required to encode the pathway for
      pyrrolnitrin biosynthesis.

PMID- 9172334
TI  - Growth and energetics of Leuconostoc mesenteroides NRRL B-1299 during metabolism
      of various sugars and their consequences for dextransucrase production.
AB  - The metabolic and energetic properties of Leuconostoc mesenteroides have been
      examined with the goal of better understanding the parameters which affect
      dextransucrase activity and hence allowing the development of strategies for
      improved dextransucrase production. Glucose and fructose support equivalent
      specific growth rates (0.6 h-1) under aerobic conditions, but glucose leads to a
      better biomass yield in anaerobiosis. Both sugars are phosphorylated by specific
      hexokinases and catabolized through the heterofermentative phosphoketolase
      pathway. During sucrose-grown cultures, a large fraction of sucrose is converted
      outside the cell by dextransucrase into dextran and fructose and does not support
      growth. The other fraction enters the cell, where it is phosphorylated by an
      inducible sucrose phosphorylase and converted to glucose-6-phosphate (G-6-P) by a
      constitutive phosphoglucomutase and to heterofermentative products (lactate,
      acetate, and ethanol). Sucrose supports a higher growth rate (0.98 h-1) than the
      monosaccharides. When fructose is not consumed simultaneously with G-1-P, the
      biomass yield relative to ATP is high (16.8 mol of ATP.mol of sucrose-1), and
      dextransucrase production is directly proportional to growth. However, when the
      fructose moiety is used, a sink of energy is observed, and dextransucrase
      production is no longer correlated with growth. As a consequence, fructose
      catabolism must be avoided to improve the amount of dextransucrase synthesized.

PMID- 9172335
TI  - Laccase isoenzymes of Pleurotus eryngii: characterization, catalytic properties,
      and participation in activation of molecular oxygen and Mn2+ oxidation.
AB  - Two laccase isoenzymes produced by Pleurotus eryngii were purified to
      electrophoretic homogeneity (42- and 43-fold) with an overall yield of 56.3%.
      Laccases I and II from this fungus are monomeric glycoproteins with 7 and 1%
      carbohydrate content, molecular masses (by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis) of 65 and 61 kDa, and pIs of 4.1 and 4.2, respectively. The
      highest rate of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) oxidation for
      laccase I was reached at 65 degrees C and pH 4, and that for laccase II was
      reached at 55 degrees C and pH 3.5. Both isoenzymes are stable at high pH,
      retaining 60 to 70% activity after 24 h from pH 8 to 12. Their amino acid
      compositions and N-terminal sequences were determined, the latter strongly
      differing from those of laccases of other basidiomycetes. Antibodies against
      laccase I reacted with laccase II, as well as with laccases from Pleurotus
      ostreatus, Pleurotus pulmonarius, and Pleurotus floridanus. Different hydroxy-
      and methoxy-substituted phenols and aromatic amines were oxidized by the two
      laccase isoenzymes from P. eryngii, and the influence of the nature, number, and
      disposition of aromatic-ring substituents on kinetic constants is discussed.
      Although both isoenzymes presented similar substrate affinities, the maximum
      rates of reactions catalyzed by laccase I were higher than those of laccase II.
      In reactions with hydroquinones, semiquinones produced by laccase isoenzymes were
      in part converted into quinones via autoxidation. The superoxide anion radical
      produced in the latter reaction dismutated, producing hydrogen peroxide. In the
      presence of manganous ion, the superoxide union was reduced to hydrogen peroxide
      with the concomitant production of manganic ion. These results confirmed that
      laccase in the presence of hydroquinones can participate in the production of
      both reduced oxygen species and manganic ions.

PMID- 9172336
TI  - Epidemiological relatedness and clonal types of natural populations of
      Escherichia coli strains producing Shiga toxins in separate populations of cattle
      and sheep.
AB  - Two separate animal populations consisting of a herd of cattle (19 animals) and a
      flock of sheep (25 animals) were investigated for strains of Escherichia coli
      producing Shiga toxins (STEC) over a time period of 6 months. Thirty-three STEC
      were isolated from 63.2% of cattle and grouped into 11 serotypes and eight
      electrophoretic types (ETs) by multilocus enzyme analysis. In sheep, 88% of the
      animals excreted STEC (n = 67 isolates) belonging to 17 different serotypes and
      12 different ETs. STEC from cattle and sheep differed with respect to serotype,
      and only 4 of the 16 ETs occurred in both animal populations. In cattle, ET14
      (O116:H21) strains predominated, whereas other STEC serotypes occurred only
      sporadically. The predominating STEC types in sheep were ET4 (O125 strains), ET11
      (O128:H2 and others), and ET14 (O146:H21). In contrast to their diversity, STEC
      originating from the same animal population were similar with respect to Shiga
      toxin (stxy genes. Almost all STEC isolated from cattle were positive for stx2
      and stx2c; only one was positive for stx1. In sheep, almost all STEC isolated
      were positive for stx1 and stx2, whereas stx2c was not found. XbaI-digested DNAs
      of genetically closely related O146:H21 strains have different restriction
      profiles which were associated with size alterations in XbaI fragments
      hybridizing with stx1- and stx2-specific DNA probes. Our results indicate that
      stx-encoding bacteriophages might be the origin of the genetic heterogeneity in
      STEC from animals.

PMID- 9172337
TI  - Bacterial population dynamics in a meromictic lake.
AB  - Polyclonal antibodies against nine different bacteria isolated from Lake
      Saelenvannet in western Norway were produced, and the population dynamics of
      these strains in the lake were monitored through two spring seasons by
      immunofluorescence staining. The total counts of bacteria varied over time and
      space from 1.5 x 10(6) to 1.5 x 10(7) cells ml-1. The counts of specific bacteria
      were in the range of 10(3) to 10(4) cells ml-1 or less; in sum, they generally
      made up less than 1% of the bacterial community. Some populations showed
      significant changes in abundance, with blooms lasting 1 to 3 weeks. The rate of
      change (increase and decrease) in abundance during blooms was estimated to be 0.2
      to 0.6 day-1. The average virus-to-bacteria ratio was 50, and there was a
      significant correlation between the abundances of virus and bacteria. Both
      protozoan grazing and lytic virus infection were assessed as possible mechanisms
      driving the variations in bacterial population density.

PMID- 9172338
TI  - Differentiation of Shewanella putrefaciens and Shewanella alga on the basis of
      whole-cell protein profiles, ribotyping, phenotypic characterization, and 16S
      rRNA gene sequence analysis.
AB  - Seventy-six presumed Shewanella putrefaciens isolates from fish, oil drillings,
      and clinical specimens, the type strain of Shewanella putrefaciens (ATCC 8071),
      the type strain of Shewanella alga (IAM 14159), and the type strain of Shewanella
      hanedai (ATCC 33224) were compared by several typing methods. Numerical analysis
      of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell
      protein and ribotyping patterns showed that the strains were separated into two
      distinct clusters with 56% +/- 10% and 40% +/- 14% similarity for whole-cell
      protein profiling and ribotyping, respectively. One cluster consisted of 26
      isolates with 52 to 55 mol% G + C and included 15 human isolates, mostly clinical
      specimens, 8 isolates from marine waters, and the type strain of S. alga. This
      homogeneous cluster of mesophilic, halotolerant strains was by all analyses
      identical to the recently defined species S. alga (U. Simidu et al., Int. J.
      Syst. Bacteriol, 40:331-336, 1990). Fifty-two typically psychrotolerant strains
      formed the other, more heterogeneous major cluster, with 43 to 47 mol% G + C. The
      type strain of S. putrefaciens was included in this group. The two groups were
      confirmed by 16S rRNA gene sequence analysis. It is concluded that the isolates
      must be considered two different species, S. alga and S. putrefaciens, and that
      most mesophilic isolates formerly identified as S. putrefaciens belong to S.
      alga. The ecological role and potential pathogenicity of S. alga can be evaluated
      only if the organism is correctly identified.

PMID- 9172339
TI  - Photoreactivation compensates for UV damage and restores infectivity to natural
      marine virus communities.
AB  - We investigated the potential for photoreactivation to restore infectivity to
      sunlight-damaged natural viral communities in offshore (chlorophyll a, < 0.1
      microgram liter-1), coastal (chlorophyll a, ca. 0.2 microgram liter-1), and
      estuarine (chlorophyll a, ca. 1 to 5 micrograms liter-1) waters of the Gulf of
      Mexico. In 67% of samples, the light-dependent repair mechanisms of the bacterium
      Vibrio natriegens restored infectivity to natural viral communities which could
      not be repaired by light-independent mechanisms. Similarly, exposure of sunlight
      damaged natural viral communities to > 312-nm-wavelength sunlight in the presence
      of the natural bacterial communities restored infectivity to 21 to 26% of
      sunlight-damaged viruses in oceanic waters and 41 to 52% of the damaged viruses
      in coastal and estuarine waters. Wavelengths between 370 and 550 nm were
      responsible for restoring infectivity to the damaged viruses. These results
      indicate that light-dependent repair, probably photoreactivation, compensated for
      a large fraction of sunlight-induced DNA damage in natural viral communities and
      is potentially essential for the maintenance of high concentrations of viruses in
      surface waters.

PMID- 9172341
TI  - Cloning and functional expression in Escherichia coli of the gene encoding the di
      and tripeptide transport protein of Lactobacillus helveticus.
AB  - The gene encoding the di- and tripeptide transport protein (DtpT) of
      Lactobacillus helveticus (DtpTLH) was cloned with the aid of the inverse PCR
      technique and used to complement the dipeptide transport-deficient and proline
      auxotrophic Escherichia coli E1772. Functional expression of the peptide
      transporter was shown by the uptake of prolyl-[14C] alanine in whole cells and
      membrane vesicles. Peptide transport via DtpT in membrane vesicles is driven by
      the proton motive force. The system has specificity for di- and tripeptides but
      not for amino acids or tetrapeptides. The dtpTLH gene consists of 1,491 bp, which
      translates into a 497-amino-acid polypeptide. DtpTLH shows 34% identity to the di
      and tripeptide transport protein of Lactococcus lactis and is also homologous to
      various peptide transporters of eukaryotic origin, but the similarity between
      these proteins is confined mainly to the N-terminal halves.

PMID- 9172340
TI  - Variation of microcystins, cyanobacterial hepatotoxins, in Anabaena spp. as a
      function of growth stimuli.
AB  - Cyanobacterial hepatotoxins, microcystins, are specific inhibitors of
      serine/threonine protein phosphatases and potent tumor promoters. They have
      caused several poisonings of animals and also pose a health hazard for humans
      through the use of water for drinking and recreation. Different strains of the
      same cyanobacterial species may variously be nontoxic, be neurotoxic, or produce
      several microcystin variants. It is poorly understood how the amount of toxins
      varies in a single strain. This laboratory study shows the importance of external
      growth stimuli in regulating the levels and relative proportions of different
      microcystin variants in two strains of filamentous, nitrogen-fixing Anabaena spp.
      The concentration of the toxins in the cells increased with phosphorus. High
      temperatures (25 to 30 degrees C), together with the highest levels of light
      studied (test range, 2 to 100 mumol m-2 s-1), decreased their amount. Different
      structural variants of microcystins responded differently to growth stimuli.
      Variants of microcystin (MCYST)-LR correlated with temperatures below 25 degrees
      C, and those of MCYST-RR correlated with higher temperatures. Nitrogen added into
      the growth medium and increasing temperatures increased the proportion of
      microcystin variants demethylated in amino acid 3. All variants remained mostly
      intracellular. Time was the most important factor causing the release of the
      toxins into the growth medium. Time, nitrogen added into the growth medium, and
      light fluxes above 25 mumol m-2 s-1 significantly increased the concentrations of
      the dissolved toxins. According to the results, it thus seems that the reduction
      of phosphorus loads in bodies of water might play a role in preventing the health
      hazards that toxic cyanobacterial water blooms pose, not only by decreasing the
      cyanobacteria but also by decreasing their toxin content.

PMID- 9172342
TI  - Dynamics of a microbial community associated with manure hot spots as revealed by
      phospholipid fatty acid analyses.
AB  - Microbial community dynamics associated with manure hot spots were studied by
      using a model system consisting of a gel-stabilized mixture of soil and manure,
      placed between layers of soil, during a 3-week incubation period. The microbial
      biomass, measured as the total amount of phospholipid fatty acids (PLFA), had
      doubled within a 2-mm distance from the soil-manure interface after 3 days.
      Principal-component analyses demonstrated that this increase was accompanied by
      reproducible changes in the composition of PLFA, indicating changes in the
      microbial community structure. The effect of the manure was strongest in the 2-mm
      thick soil layer closest to the interface, in which the PLFA composition was
      statistically significantly different (P < 0.05) from that of the unaffected soil
      layers throughout the incubation period. An effect was also observed in the soil
      layer 2 to 4 mm from the interface. The changes in microbial biomass and
      community structure were mainly attributed to the diffusion of dissolved organic
      carbon from the manure. During the initial period of microbial growth, PLFA,
      which were already more abundant in the manure than in the soil, increased in the
      manure core and in the 2-mm soil layer closest to the interface. After day 3, the
      PLFA composition of these layers gradually became more similar to that of the
      soil. The dynamics of individual PLFA suggested that both taxonomic and
      physiological changes occurred during growth. Examples of the latter were
      decreases in the ratios of 16:1 omega 7t to 16:1 omega 7c and of cyclopropyl
      fatty acids to their respective precursors, indicating a more active bacterial
      community. An inverse relationship between bacterial PLFA and the eucaryotic 20:4
      PLFA (arachidonic acid) suggested that grazing was important.

PMID- 9172343
TI  - Sequencing and functional analysis of styrene catabolism genes from Pseudomonas
      fluorescens ST.
AB  - The nucleotide sequence of the 4,377-bp chromosomal region of Pseudomonas
      fluorescens ST that codes for the oxidation of styrene to phenylacetic acid was
      determined. Four open reading frames, named styA, styB, styC, and styD, were
      identified in this region. Sequence analysis and biotransformation assays,
      performed with batch and continuous cultures, allowed us to identify the
      functions of the sequenced genes. styA and styB encode a styrene monooxygenase
      responsible for the transformation of styrene to epoxystyrene; styC codes for the
      second enzyme of the pathway, an epoxystyrene isomerase that converts
      epoxystyrene to phenylacetaldehyde; and the styD gene produces a
      phenylacetaldehyde dehydrogenase that oxidizes phenylacetaldehyde to phenylacetic
      acid. StyA, 415-amino-acids long, was found to be weakly homologous to p
      hydroxybenzoate hydroxylase from both P. fluorescens and P. aeruginosa and to
      salicylate hydroxylase from P. putida, suggesting that it might be a flavin
      adenine dinucleotide-binding monooxygenase. StyB was found to be partially
      homologous to the carboxyterminal part of the 2,4-dichlorophenol-6-monooxygenase
      encoded by plasmid pJP4, while the styC product did not share significant
      homology with any known proteins. The fourth open reading frame, styD, could
      encode a protein of 502 amino acids and was strongly homologous to several
      eukaryotic and prokaryotic aldehyde dehydrogenases. The order of the genes
      corresponds to that of the catabolic steps. The previously suggested presence of
      the gene for epoxystyrene reductase, which directly converts epoxystyrene to 2
      phenylethanol (A.M. Marconi, F. Beltrametti, G. Bestetti, F. Solinas, M. Ruzzi,
      E. Galli, and E. Zennaro, Appl. Environ. Microbiol. 61:121-127, 1996), has not
      been confirmed by sequencing and by biotransformation assays performed in
      continuous cultures. A copy of the insertion sequence ISI162, belonging to the
      IS21-like family of elements, was identified immediately downstream of the
      styrene catabolic genes.

PMID- 9172344
TI  - The methanogenic archaeon Methanosarcina thermophila TM-1 possesses a high
      affinity glycine betaine transporter involved in osmotic adaptation.
AB  - Methanogenic Archaea are found in a wide range of environments and use several
      strategies to adjust to changes in extracellular solute concentrations. One
      methanogenic archaeon, Methanosarcina thermophila TM-1, can adapt to various
      osmotic conditions by synthesis of alpha-glutamate and a newly discovered
      compatible solute, Ne-acetyl-beta-lysine, or by accumulation of glycine betaine
      (betaine) and potassium ions from the environment. Since betaine transport has
      not been characterized for any of the methanogenic Archaea, we examined the
      uptake of this solute by M. thermophila TM-1. When cells were grown in mineral
      salts media containing from 0.1 to 0.8 M NaC1, M. thermophila accumulated betaine
      in concentrations up to 140 times those of a concentration gradient within 10 min
      of exposure to the solute. The betaine uptake system consisted of a single, high
      affinity transporter with an apparent K3 of 10 microM and an apparent maximum
      transport velocity of 1.15 nmol/min/mg of protein. The transporter appeared to be
      specific for betaine, since potential substrates, including glycine, sarcosine,
      dimethyl glycine, choline, and proline, did not significantly inhibit betaine
      uptake. M. thermophila TM-1 cells can also regulate the capacity for betaine
      accumulation, since the rate of betaine transport was reduced in cells pregrown
      in a high-osmolarity medium when 500 microM betaine was present. Betaine
      transport appears to be H+ and/or Na+ driven, since betaine transport was
      inhibited by several types of protonophores and sodium ionophores.

PMID- 9172345
TI  - Detection of RTX toxin genes in gram-negative bacteria with a set of specific
      probes.
AB  - The family of RTX (RTX representing repeats in the structural toxin) toxins is
      composed of several protein toxins with a characteristic nonapeptide glycine-rich
      repeat motif. Most of its members were shown to have cytolytic activity. By
      comparing the genetic relationships of the RTX toxin genes we established a set
      of 10 gene probes to be used for screening as-yet-unknown RTX toxin genes in
      bacterial species. The probes include parts of apxIA, apxIIA, and apxIIIA from
      Actinobacillus pleuropneumoniae, cyaA from Bordetella pertusis, frpA from
      Neisseria meningitidis, prtC from Erwinia chrysanthemi, hlyA and elyA from
      Escherichia coli, aaltA from Actinobacillus actinomycetemcomitans and lktA from
      Pasteurella haemolytica. A panel of pathogenic and nonpathogenic gram-negative
      bacteria were investigated for the presence of RTX toxin genes. The probes
      detected all known genes for RTX toxins. Moreover, we found potential RTX toxin
      genes in several pathogenic bacterial species for which no such toxins are known
      yet. This indicates that RTX or RTX-like toxins are widely distributed among
      pathogenic gram-negative bacteria. The probes generated by PCR and the
      hybridization method were optimized to allow broad-range screening for RTX toxin
      genes in one step. This included the binding of unlabelled probes to a nylon
      filter and subsequent hybridization of the filter with labelled genomic DNA of
      the strain to be tested. The method constitutes a powerful tool for the
      assessment of the potential pathogenicity of poorly characterized strains
      intended to be used in biotechnological applications. Moreover, it is useful for
      the detection of already-known or new RTX toxin genes in bacteria of medical
      importance.

PMID- 9172346
TI  - Pristine environments harbor a new group of oligotrophic 2,4
      dichlorophenoxyacetic acid-degrading bacteria.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D)-degrading bacteria were isolated from
      pristine environments which had no history of 2,4-D exposure. By using 2,4-D dye
      indicator medium or 14C-labeled 2,4-D medium, six strains were isolated from
      eight enrichment cultures capable of degrading 2,4-D. Phylogenetic analyses based
      on 16S ribosomal DNA (rDNA) sequencing and physiological properties revealed that
      one isolate from Hawaiian volcanic soil could be classified in the genus
      Variovorax (a member of the beta subdivision of the class Proteobacteria) and
      that the other five isolates from Hawaiian volcanic soils, Saskatchewan forest
      soil, and Chilean forest soil have 16S rDNAs with high degrees of similarity to
      those of the Bradyrhizobium group (a member of the alpha subdivision of the class
      Proteobacteria). All the isolates grow slowly on either nutrient media (0.1 x
      Bacto Peptone-tryptone-yeast extract-glucose [PTYG] or 0.1 x Luria broth [LB]
      medium) or 2,4-D medium, with mean generation times of 16 to 30 h, which are
      significantly slower than previously known 2,4-D degraders. Nutrient-rich media
      such as full-strength PTYG and LB medium did not allow their growth. PCR
      amplification using internal consensus sequences of tfdA (a gene encoding an
      enzyme for the first step of 2,4-D mineralization, found in pJP4 of Alcaligenes
      eutrophus JMP134 and some other 2,4-D-degrading bacteria) as primers and Southern
      hybridization with pJP4-tfdA as a probe revealed that the isolate belonging to
      the genus Variovorax carried the tfdA gene. This gene was transmissible to A.
      eutrophus JMP228 carrying a plasmid with a mutant tfdA gene. The other five
      isolates did not appear to carry tfdA, and 2,4-D-specific alpha-ketoglutarate
      dependent dioxygenase activity could not be detected in cell lysates. These
      results indicate that 2,4-D-degrading bacteria in pristine environments are slow
      growing bacteria and that most of their phylogenies and catabolic genes differ
      from those of 2,4-D degraders typically isolated from agricultural soils or
      contaminated environments.

PMID- 9172347
TI  - Cloning, sequencing, and overexpression of the Anaerobiospirillum
      succiniciproducens phosphoenolpyruvate carboxykinase (pckA) gene.
AB  - The phosphoenolpyruvate (PEP) carboxykinase-encoding gene from the anaerobic, CO2
      fixing, succinate-producing bacterium Anaerobiospirillum succiniciproducens was
      cloned, sequenced, and expressed in Escherichia coli. The gene encoded a 532
      residue polypeptide with a calculated molecular mass of 58.7 kDa. The sequence of
      the A. succiniciproducens PEP carboxykinase was similar to those of all known
      ATP/ADP-dependent PEP carboxykinases. In particular, the A. succiniciproducens
      enzyme was 67.3% identical and 79.2% similar to the E. coli enzyme. The A.
      succiniciproducens pckA transcription start site was determined, and putative
      promoter regions were identified. The recombinant enzyme was overexpressed in E.
      coli. The purified enzyme was indiscernible from the native enzyme by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and had the same activity as
      the native enzyme.

PMID- 9172348
TI  - Cell density-regulated recovery of starved biofilm populations of ammonia
      oxidizing bacteria.
AB  - The speed of recovery of cell suspensions and biofilm populations of the ammonia
      oxidizer Nitrosomonas europaea, following starvation was determined. Stationary
      phase cells, washed and resuspended in ammoniumfree inorganic medium, were
      starved for periods of up to 42 days, after which the medium was supplemented
      with ammonium and subsequent growth was monitored by measuring nitrite
      concentration changes. Cultures exhibited a lag phase prior to exponential
      nitrite production, which increased from 8.72 h (no starvation) to 153 h after
      starvation for 42 days. Biofilm populations of N. europaea colonizing sand or
      soil particles in continuous-flow, fixed column reactors were starved by
      continuous supply of ammonium-free medium. Following resupply of ammonium,
      starved biofilms exhibited no lag phase prior to nitrite production, even after
      starvation for 43.2 days, although there was evidence of cell loss during
      starvation. Biofilm formation will therefore provide a significant ecological
      advantage for ammonia oxidizers in natural environments in which the substrate
      supply is intermittent. Cell density-dependent phenomena in a number of gram
      negative bacteria are mediated by N-acyl homoserine lactones (AHL), including N
      (3-oxohexanoyl)-L-homoserine lactone (OHHL). Addition of both ammonium and OHHL
      to cell suspensions starved for 28 days decreased the lag phase in a
      concentration-dependent manner from 53.4 h to a minimum of 10.8 h. AHL production
      by N. europaea was detected by using a luxR-luxAB AHL reporter system. The
      results suggest that rapid recovery of high-density biofilm populations may be
      due to production and accumulation of OHHL to levels not possible in relatively
      low-density cell suspensions.

PMID- 9172349
TI  - Isolation and properties of Lactococcus lactis subsp. lactis biovar diacetylactis
      CNRZ 483 mutants producing diacetyl and acetoin from glucose.
AB  - Following treatment with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine, three
      mutants of Lactococcus lactis subsp. lactis biovar diacetylactis CNRZ 483 that
      produced diacetyl and acetoin from glucose were isolated. The lactate
      dehydrogenase activity of these mutants was strongly attenuated, and the mutants
      produced less lactate than the parental strain. The kinetic properties of lactate
      dehydrogenase of strain CNRZ 483 and the mutants revealed differences in the
      affinity of the enzyme for pyruvate, NADH, and fructose-1,6-diphosphate. When
      cultured aerobically, strain CNRZ 483 transformed 2.3% of glucose to acetoin and
      produced no diacetyl or 2,3-butanediol. Under the same conditions, mutants 483L1,
      483L2, and 483L3 transformed 42.0, 78.9, and 75.8%, respectively, of glucose to
      C4 compounds (diacetyl, acetoin, and 2,3-butanediol). Anaerobically, strain CNRZ
      483 produced no C4 compounds, while mutants 483L1, 483L2, and 483L3 transformed
      2.0, 37.0, and 25.8% of glucose to acetoin and 2,3-butanediol. In contrast to the
      parental strain, the NADH balance showed that the mutants regenerated most of the
      NAD via NADH oxidase under aerobic conditions and by ethanol production under
      anaerobic conditions.

PMID- 9172350
TI  - Cloning of the nprA gene for neutral protease A of Bacillus thuringiensis and
      effect of in vivo deletion of nprA on insecticidal crystal protein.
AB  - The nprA gene, encoding Bacillus thuringiensis neutral protease A, was cloned by
      the use of gene-specific oligonucleotides. The size of neutral protease A deduced
      from the nprA sequence was 566 amino acids (60,982 Da). The cloned nprA gene was
      partially deleted in vitro, and the deleted allele, designated nprA3, was used to
      construct an nprA3 strain (neutral protease A-deficient strain) of B.
      thuringiensis. Growth and sporulation of the nprA3 strain were similar to those
      of an isogenic nprA+ strain, although the extracellular proteolytic activity of
      the nprA3 strain was significantly less than that of the nprA+ strain. The nprA3
      strain produced insecticidal crystal proteins that were more stable than those of
      the isogenic nprA+ strain after solubilization in vitro, and sporulated cultures
      of the nprA3 strain contained higher concentrations of full-length insecticidal
      crystal proteins than did those of its isogenic counterpart. The absence of
      neutral protease A did not affect the insecticidal activity of a lepidopteran
      specific crystal protein of B. thuringiensis. These results indicate that crystal
      protein stability and yield may be improved by deletion of specific proteases
      from B. thuringiensis.

PMID- 9172351
TI  - Isolation and characterization of fimbriae from a sparsely fimbriated strain of
      Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis W50 (ATCC 53978) possesses the gene for fimbriae;
      however, the surface-expressed fimbriae are sparse and have not been previously
      isolated and characterized. We purified fimbriae from strain W50 to homogeneity
      by ammonium sulfate precipitation and reverse-phase high-performance liquid
      chromatography [H. T. Sojar, N. Hamada, and R. J. Genco, Protein Expr. Purif.
      9(1):49-52, 1997]. Negative staining of purified fimbriae viewed by electron
      microscopy revealed that the fimbriae were identical in diameter to fimbriae of
      other P. gingivalis strains, such as 2561, but were shorter in length. On sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the
      apparent molecular weight of isolated fimbrillin from strain W50 was found to be
      identical to that of the fimbrillin molecule of strain 2561. Unlike 2561
      fimbriae, W50 fimbriae, under reducing condition, exhibited a monomeric structure
      on SDS-PAGE at room temperature. However, under nonreduced conditions, even at
      100 degrees C, no monomer was observed. In immunoblot analysis as well as
      immunogold labeling of isolated fimbriae, polyclonal antibodies against 2561
      fimbriae, as well as antibodies against peptide I (V-V-M-A-N-T-G-A-M-E-V-G-K-T-L
      A-E-V-K-Cys) and peptide J (A-L-T-T-E-L-T-A-E-N-Q-E-A-A-G-L-I-M-T-A-E-P-Cys),
      reacted. However, antifimbrial antibodies against strain 2561 reacted very weakly
      compared to anti-peptide I and anti-peptide J. Negative staining of whole W50
      cells, as well as immunogold electron microscopy with anti-peptide I and anti
      peptide J, showed fimbriae shorter in length and very few in number compared to
      those of strain 2561. Purified fimbriae showed no hemagglutinating activity.
      Amino acid composition was very similar to that of previously reported fimbriae
      of the 2561 strain.

PMID- 9172352
TI  - Natural horizontal transfer of a naphthalene dioxygenase gene between bacteria
      native to a coal tar-contaminated field site.
AB  - Horizontal transfer of genes responsible for pollutant biodegradation may play a
      key role in the evolution of bacterial populations and the adaptation of
      microbial communities to environmental contaminants. However, field evidence for
      horizontal gene transfer between microorganisms has traditionally been very
      difficult to obtain. In this study, the sequences of the 16S rRNA and naphthalene
      dioxygenase iron-sulfur protein (nahAc) genes of nine naphthalene-degrading
      bacteria isolated from a coal tar waste-contaminated site, as well as a
      naphthalene-degrading bacterium from a contaminated site in Washington state and
      two archetypal naphthalene-degrading strains, were compared. Seven strains from
      the study site had a single nahAc allele, whereas the 16S rRNA gene sequences of
      the strains differed by as much as 7.9%. No nahAc alleles from the site were
      identical to those of the archetypal strains, although the predominant allele was
      closely related to that of Pseudomonas putida NCIB 9816-4, isolated in the
      British Isles. However, one site-derived nahAc allele was identical to that of
      the Washington state strain. Lack of phylogenetic congruence of the nahAc and 16S
      rRNA genes indicates that relatively recent in situ horizontal transfer of the
      nahAc gene has occurred, possibly as a direct or indirect consequence of
      pollutant contamination. Alkaline lysis plasmid preparations and pulsed-field gel
      electrophoresis have revealed the presence of plasmids ranging in size from 70 to
      88 kb in all site isolates. Southern hybridizations with a 407-bp nahAc probe
      have suggested that the nahAc gene is plasmid borne in all the site isolates but
      one, a strain isolated from subsurface sediment 400 m upstream from the source of
      the other site isolates. In this strain and in the naphthalene-degrading strain
      from Washington state, nahAc appears to be chromosomally located. In addition,
      one site isolate may carry nahAc on both chromosome and plasmid. Within the group
      of bacteria with identical nahAc sequences the Southern hybridizations showed
      that the gene was distributed between plasmids of different sizes and a
      chromosome. This suggests that plasmid modification after transfer may have been
      effected by transposons. Horizontal transfer of catabolic genes may play a
      significant role in the acclimation of microbial communities to pollutants.

PMID- 9172353
TI  - A new computational method for detection of chimeric 16S rRNA artifacts generated
      by PCR amplification from mixed bacterial populations.
AB  - A new computational method (chimeric alignment) has been developed to detect
      chimeric 16S rRNA artifacts generated during PCR amplification from mixed
      bacterial populations. In contrast to other nearest-neighbor methods (e.g.,
      CHECK_CHIMERA) that define sequence similarity by k-tuple matching, the chimeric
      alignment method uses the score from dynamic programming alignments. Further, the
      chimeric alignments are displayed to the user to assist in sequence
      classification. The distribution of improvement scores for 500 authentic,
      nonchimeric sequences and 300 artificial chimeras (constructed from authentic
      sequences) was used to study the sensitivity and accuracy of both chimeric
      alignment and CHECK_CHIMERA. At a constant rate of authentic sequence
      misclassification (5%), chimeric alignment incorrectly classified 13% of the
      artificial chimeras versus 14% for CHECK_CHIMERA. Interestingly, only 1% of
      nonchimeras and 10% of chimeras were misclassified by both programs, suggesting
      that optimum performance is obtained by using the two methods to assign sequences
      to three classes: high-probability nonchimeras, high-probability chimeras, and
      sequences that need further study by other means. This study suggests that k
      tuple-based matching methods are more sensitive than alignment-based methods when
      there is significant parental sequence similarity, while the opposite becomes
      true as the sequences become more distantly related. The software and a World
      Wide Web-based server are available at http://www-hto.usc.edu/software/mglobal
      CHI.

PMID- 9172355
TI  - Modelling the growth rate of Escherichia coli as a function of pH and lactic acid
      concentration.
AB  - The growth rate responses of Escherichia coli M23 (a nonpathogenic strain) to
      suboptimal pH and lactic acid concentration were determined. Growth rates were
      measured turbidimetrically at 20 degrees C in the range of pH 2.71 to 8.45. The
      total concentration of lactic acid was fixed at specific values, and the pH was
      varied by the addition of a strong acid (hydrochloric) or base (sodium hydroxide)
      to enable the determination of undissociated and dissociated lactic acid
      concentrations under each condition. In the absence of lactic acid, E. coli grew
      at pH 4.0 but not at pH 3.7 and was unable to grow in the presence of > or = 8.32
      mM undissociated lactic acid. Growth rate was linearly related to hydrogen ion
      concentration in the absence of lactic acid. In the range 0 to 100 mM lactic
      acid, growth rate was also linearly related to undissociated lactic acid
      concentration. A mathematical model to describe these observations was developed
      based on a Belehradek-like model for the effects of water activity and
      temperature. This model was expanded to describe the effects of pH and lactic
      acid by the inclusion of novel terms for the inhibition due to the presence of
      hydrogen ions, undissociated lactic acid, and dissociated lactic acid species.
      Preliminary data obtained for 200 and 500 mM total lactic acid concentrations
      show that the response to very high lactic acid concentrations was less well
      described by the model. However, for 0 to 100 mM lactic acid, the model described
      well the qualitative and quantitative features of the response.

PMID- 9172356
TI  - In vitro assay of Staphylococcus aureus enterotoxin A activity in food.
AB  - Staphylococcus aureus enterotoxin A (SEA) is a leading cause of food poisoning.
      The current test for functional activity of SEA requires monkeys or kittens. The
      major drawbacks of animal assays are lack of quantitation, poor reproducibility,
      low sensitivity, and high cost. In this report we describe and evaluate an
      alternative assay using T-cell proliferation to measure SEA activity in food.
      Human and rat lymphocytes proliferate in response to concentrations of SEA as low
      as 1 pg/ml, well below the pathogenic dose of 100 ng. This proliferation assay is
      highly sensitive, quantitative, and simple. Nonradioactive assays of T-cell
      proliferation were also suitable for detecting and measuring SEA, although with a
      10-fold lower sensitivity. To evaluate the utility of this assay for food
      testing, four different food samples were mixed with SEA. In each sample, SEA was
      detected at a concentration of 1 ng/ml. Heat-inactivated SEA produced no
      detectable proliferation. These results demonstrate that an in vitro cell
      proliferation assay is an advantageous alternative to existing animal assays for
      measuring SEA activity in food.

PMID- 9172357
TI  - Silencing MIG1 in Saccharomyces cerevisiae: effects of antisense MIG1 expression
      and MIG1 gene disruption.
AB  - Silencing of MIG1, a transcription factor imposing carbon catabolite repression
      on invertase, was attempted, either by disrupting the gene or by expressing
      antisense copies of the gene. The performance of the recombinant strains in
      bioreactor batch cultivations on sucrose, in the presence of glucose, was
      compared with that of the wild-type strain under the same conditions. In the
      delta migI strain, the rate of sucrose utilization was independent (10 mmol/g/h)
      of the glucose concentration. During the cultivations with the wild-type strain
      and the antisense strains, two distinct phases were observed. The rates of
      sucrose hydrolysis were < 1 mmol/g/h and 9 to 10 mmol/g/h in the first and second
      phases, respectively. Entry into the second cultivation phase was characterized
      by a decline in glucose concentration below 12 mmol/liter. As expected,
      disruption of MIG1 resulted in a relief of glucose repression. However, silencing
      of MIG1 expression was not achieved by expressing antisense MIG1, even though
      antisense MIG1 RNA was sufficiently stable to be detected. In the wild-type and
      delta migI strains, the specific growth rate was 0.32 to 0.33 h-1, whereas it was
      lower in the antisense strains, 0.25 to 0.30 h-1.

PMID- 9172358
TI  - Effect of bile on Vibrio parahaemolyticus.
AB  - Many enteric pathogens are thought to enter a viable but nonculturable state when
      deprived of nutrients. Virulent strains of the enteric pathogen Vibrio
      parahaemolyticus are rarely isolated from their low-nutrient aquatic
      environments, possibly due to their nonculturability. Host factors such as bile
      may trigger release from dormancy and increase virulence in these strains. In
      this study, the addition of bile or the bile acid deoxycholic acid to estuarine
      water-cultured bacteria led to an increase in the direct viable count and colony
      counts among the virulent strains. This effect was not demonstrated in the
      nonvirulent strains, and it was reversed by extraction of bile acids with
      cholestyramine. Bile-treated V. parahaemolyticus had lower levels of
      intracellular calcium than untreated cells, and this effect coincided with an
      increase in the number of metabolically active cells. Chelation of intracellular
      calcium with BAPTA/AM (R. Y. Tsien, Biochemistry 19:2396-2402, 1980) produced
      similar results. Addition of bile to V. parahaemolyticus cultures in laboratory
      medium enhanced factors associated with virulence such as Congo red binding,
      bacterial capsule size, and adherence to epithelial cells. These results suggest
      that a bile acid-containing environment such as that found in the human host
      favors growth of virulent strains of V. parahaemolyticus and that bile acids
      enhance the expression of virulence factors. These effects seem to be mediated by
      a decrease in intracellular calcium.

PMID- 9172359
TI  - Sensitive detection of a novel class of toluene-degrading denitrifiers, Azoarcus
      tolulyticus, with small-subunit rRNA primers and probes.
AB  - Azoarcus tolulyticus is a new class of widely distributed toluene-degrading
      denitrifiers of potential importance in remediating benzene, toluene,
      ethylbenzene, and xylene (BTEX)-contaminated environments. To detect these
      organisms in the environment, 16S rRNA gene-based phylogenetic probes were
      developed. Two sets of specific PCR amplification primers and two oligonucleotide
      hybridization probes were designed and tested against both closely and distantly
      related environmental isolates. All of these primers and probes were specific to
      the species A. tolulyticus. The sensitivity of the PCR amplification primer sets
      was evaluated with DNA isolated from A. tolulyticus Tol-4 pure culture and from
      sterile soils seeded with a known number of Tol-4 and Escherichia coli cells.
      These primer sets were able to detect 1 fg to 1 pg of template DNA from the pure
      culture and 1.11 x 10(2) to 1.1 x 10(8) Tol-4 cells per g of soil in the presence
      of 1.56 x 10(10) E. coli cells. These two PCR amplification primers were also
      successfully tested at two field sites. The primers identified the A. tolulyticus
      strains among the toluene-degrading bacteria isolated from a low-O2-high-NO(3)-
      aquifer at Moffett Field, Calif. Also, the presence of A. tolulyticus was
      detected in the groundwater samples from a BTEX-contaminated aquifer at an
      industrial site in Detroit, Mich., which showed anaerobic toluene degradation.

PMID- 9172361
TI  - Oligonucleotide microchips as genosensors for determinative and environmental
      studies in microbiology.
AB  - The utility of parallel hybridization of environmental nucleic acids to many
      oligonucleotides immobilized in a matrix of polyacrylamide gel pads on a glass
      slide (oligonucleotide microchip) was evaluated. Oligonucleotides complementary
      to small-subunit rRNA sequences of selected microbial groups, encompassing key
      genera of nitrifying bacteria, were shown to selectively retain labeled target
      nucleic acid derived from either DNA or RNA forms of the target sequences. The
      utility of varying the probe concentration to normalize hybridization signals and
      the use of multicolor detection for simultaneous quantitation of multiple probe
      target populations were demonstrated.

PMID- 9172362
TI  - Conjugative plasmids and the degradation of arylsulfonates in Comamonas
      testosteroni.
AB  - Comamonas testosteroni T-2 degrades p-toluenesulfonate (TSA) via p-sulfobenzoate
      (PSB) and protocatechuate and degrades toluenecarboxylate via terephthalate (TER)
      and protocatechuate. The appropriate genes are expressed in at least five
      regulatory units, some of which are also found in C. testosteroni PSB-4 (F.
      Junker, R. Kiewitz, and A. M. Cook, J. Bacteriol. 179:919-927, 1997). C.
      testosteroni T-2 was found to contain two plasmids, pTSA (85 kbp) and pT2T (50
      kbp); a TSA- mutant (strain TER-1) contained only plasmid pT2T. C. testosteroni
      PSB-4, which does not degrade TSA, contained one plasmid, pPSB (85 kbp). The type
      strain contained no plasmids. Conjugation experiments showed that plasmid pTSA
      (possibly in conjunction with pT2T) was conjugative, and the single copy of the
      TSA operon (tsaMBCD) with its putative regulator gene (tsaR) in strain T-2 was
      found on plasmid pTSA, which also carried the PSB genes (psbAC) and presumably
      transport for both substrates. Plasmid pTSA was assigned to the IncP1 beta group
      and was found to carry two copies of insertion element IS1071. Plasmid pPSB (of
      strain PSB-4), which could be maintained in strains with plasmid pTSA or pT2T,
      was also conjugative and was found to carry the PSB genes as well as to contain
      two copies of IS1071. In attempted conjugations with the type strain, no plasmid
      was recovered, but the PSB+ transconjugant carried two copies of IS1071 in the
      chromosome. We presume the PSB genes to be located in a composite transposon. The
      genes encoding the putative TER operon and degradation of protocatechuate, with
      the meta cleavage pathway, were attributed a chromosomal location in strains T-2
      and PSB-4.

PMID- 9172363
TI  - An immunological approach to detect phosphate stress in populations and single
      cells of photosynthetic picoplankton.
AB  - In the marine cyanobacterium Synechococcus sp. strain WH7803, PstS is a 32-kDa
      cell wall-associated phosphate-binding protein specifically synthesized under
      conditions of restricted inorganic phosphate (P1) availability (D. J. Scanlan, N.
      H. Mann, and N. G. Carr, Mol. Microbiol. 10:181-191, 1993). We have assessed its
      use as a potential diagnostic marker for the P status of photosynthetic
      picoplankton. Expression of PstS in Synechococcus sp. strain WH7803 was observed
      when the P1 concentration fell below 50 nM, demonstrating that the protein is
      induced at concentrations of P1 typical of oligotrophic conditions. PstS
      expression could be specifically detected by use of standard Western blotting
      (immunoblotting) techniques in natural mesocosm samples under conditions in which
      the N/P ratio was artificially manipulated to force P depletion. In addition, we
      have developed an immunofluorescence assay that can detect PstS expression in
      single Synechococcus cells both in laboratory cultures and natural samples. We
      show that antibodies raised against PstS cross-react with P-depleted
      Prochlorococcus cells, extending the use of these antibodies to both major groups
      of prokaryotic photosynthetic picoplankton. Furthermore, DNA sequencing of a
      Prochlorococcus pstS homolog demonstrated high amino acid sequence identity (77%)
      with the marine Synechococcus sp. strain WH7803 protein, including those residues
      in Escherichia coli PstS known to be directly involved in phosphate binding.

PMID- 9172364
TI  - Bacterial viability and antibiotic susceptibility testing with SYTOX green
      nucleic acid stain.
AB  - A fluorescent nucleic acid stain that does not penetrate living cells was used to
      assess the integrity of the plasma membranes of bacteria. SYTOX Green nucleic
      acid stain is an unsymmetrical cyanine dye with three positive charges that is
      completely excluded from live eukaryotic and prokaryotic cells. Binding of SYTOX
      Green stain to nucleic acids resulted in a > 500-fold enhancement in fluorescence
      emission (absorption and emission maxima at 502 and 523 nm, respectively),
      rendering bacteria with compromised plasma membranes brightly green fluorescent.
      SYTOX Green stain is readily excited by the 488-nm line of the argon ion laser.
      The fluorescence signal from membrane-compromised bacteria labeled with SYTOX
      Green stain was typically > 10-fold brighter than that from intact organisms.
      Bacterial suspensions labeled with SYTOX Green stain emitted green fluorescence
      in proportion to the fraction of permeabilized cells in the population, which was
      quantified by microscopy, fluorometry, or flow cytometry. Flow cytometric and
      fluorometric approaches were used to quantify the effect of beta-lactam
      antibiotics on the cell membrane integrity of Escherichia coli. Detection and
      discrimination of live and permeabilized cells labeled with SYTOX Green stain by
      flow cytometry were markedly improved over those by propidium iodide-based tests.
      These studies showed that bacterial labeling with SYTOX Green stain is an
      effective alternative to conventional methods for measuring bacterial viability
      and antibiotic susceptibility.

PMID- 9172365
TI  - Construction of specific erythromycin resistance mutations in the temperate
      lactococcal bacteriophage TP901-1 and their use in studies of phage biology.
AB  - A method for the construction and isolation of specifically designed mutations of
      the temperate lactococcal phage TP901-1 has been developed. Two different erm
      labeled mutants were isolated. One was shown to be defective in lysogenization
      and excision. The other, showing normal lysogenization, was used for host range
      studies.

PMID- 9172366
TI  - Construction and characterization of Escherichia coli genetically engineered for
      bioremediation of Hg(2+)-contaminated environments.
AB  - Escherichia coli strains were genetically engineered to express an Hg2+ transport
      system and metallothionein. Overexpression of a glutathione S-transferase fusion
      protein of Saccharomyces cerevisiae or pea metallothionein significantly
      increased the bioaccumulation of Hg2+ transported by MerT and MerP and protected
      the cells from the accumulated Hg2+. The recombinant strains have excellent
      properties for bioremediation of Hg(2+)-contaminated environments.

PMID- 9172367
TI  - Catalytic properties of the cellulose-binding endoglucanase F from Fibrobacter
      succinogenes S85.
AB  - The celF gene from the predominant cellulolytic ruminal bacterium Fibrobacter
      succinogenes encodes a 118.3-kDa cellulose-binding endoglucanase, endoglucanase F
      (EGF). This enzyme possesses an N-terminal cellulose-binding domain and a C
      terminal catalytic domain. The purified catalytic domain displayed an activity
      profile typical of an endoglucanase, with high catalytic activity on
      carboxymethyl cellulose and barley beta-glucan. Immunoblotting of EGF and the
      formerly characterized endoglucanase 2 (EG2) from F. succinogenes with antibodies
      prepared against each of the enzymes demonstrated that EGF and EG2 contain cross
      reactive epitopes. This data in conjunction with evidence that the proteins are
      the same size, share a 19-residue internal amino acid sequence, possess similar
      catalytic properties, and both bind to cellulose allows the conclusion that celF
      codes for EG2.

PMID- 9172368
TI  - Cloning and sequence analysis of putative histidine protein kinases isolated from
      Lactococcus lactis MG1363.
AB  - Eight recombinant plasmids harboring chromosomal fragments of Lactococcus lactis
      MG1363 were shown to phenotypically suppress a histidine protein kinase (HPK)
      deficiency in either of two different E. coli strains. Sequence analysis of the
      plasmid inserts revealed five different complete or partial open reading frames
      (ORFs) specifying proteins with high similarity to HPKs. One of the plasmids also
      harbored an additional ORF, unrelated to HPKs, with suppressing activity.

PMID- 9172369
TI  - Detection of hepatitis A virus RNA in oyster meat.
AB  - Detection of low concentrations of viruses in shellfish is possible with nucleic
      acid amplification by PCR. Hepatitis A virus (HAV) has been detected in oyster
      meat by reverse transcription-PCR (RT-PCR). We developed a method to identify HAV
      RNA by RT-PCR of total RNA extracted from oyster meat contaminated by adsorption,
      bioaccumulation, or injection. With dot blot hybridization detection of amplicons
      from the RT-PCR, rapid screening of a large number of samples is feasible. As few
      as 8 PFU of HAV/g of oyster meat can be detected.

PMID- 9172370
TI  - Distribution of Vibrio vulnificus phage in oyster tissues and other estuarine
      habitats.
AB  - Phages lytic to Vibrio vulnificus were found in estuarine waters, sediments,
      plankton, crustacea, molluscan shellfish, and the intestines of finfish of the
      U.S. Gulf Coast, but no apparent relationship between densities of V. vulnificus
      and its phages was observed. Phage diversity and abundance in molluscan shellfish
      were much greater than in other habitats. V. vulnificus phages isolated from
      oysters did not lyse other mesophilic bacteria also isolated from oysters. Both
      V. vulnificus and its phages were found in a variety of oyster tissues and fluids
      with lowest densities in the hemolymph and mantle fluid. These findings suggest a
      close ecological relationship between V. vulnificus phages and molluscan
      shellfish.

PMID- 9172371
TI  - Specificity of an extracellular proteinase from Brevibacterium linens ATCC 9174
      on bovine beta-casein.
AB  - The specificity of the extracellular proteinase from Brevibacterium linens ATCC
      9174 on bovine beta-casein was studied. Hydrolysis was monitored over time by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) and urea-PAGE.
      The major pH 4.6-soluble peptides were isolated by high-performance liquid
      chromatography and identified by N-terminal amino acid sequencing and mass
      spectrometry. The major sites of hydrolysis were Ser-18-Ser-19, Glu-20-Glu-21,
      Gln-56-Ser-57, Gln-72-Asn-73, Leu-77-Thr-78, Ala-101-Met-102, Phe-119-Thr-120,
      Leu-139-Leu-140, Ser-142-Trp-143, His-145-Gln-146, Gln-167-Ser-168, Gln-175-Lys
      176, Tyr-180-Pro-181, and Phe-190-Leu-191. The proteinase had a broad specificity
      for the amino acid residues present at the P1 and P'1 positions but showed a
      preference for hydrophobic residues at the P2, P3, P4, P'2, P'3, and P'4
      positions.

PMID- 9172374
TI  - Urea and amphibian water economy.
AB  - Accumulation of urea in the body fluids enables some amphibians to tolerate high
      ambient salinities (Bufo viridis, Xenopus laevis, Rana cancrivora, Ambystoma
      tigrinum, Batrachoseps spp.) or to estivate in soil with low water potentials
      (Scaphiopus spp.). These species are assumed not only to accumulate urea produced
      in the normal metabolism, but to synthesize urea in response to water shortage.
      Re-examination of the data did not support the view of an osmoregulatory urea
      synthesis. Increased urea synthesis on exposure to high salinities in X. laevis,
      R. cancrivora and Batrachoseps spp. seemed to reflect reactions to an adverse
      environment. It is suggested that in amphibians, solute concentration in the
      plasma and rate of excretion of urea are coordinated so that at a certain plasma
      concentration, urea is excreted at the same rate at which it is produced. The
      higher the level of urea in the body fluids at balance between production and
      excretion, the higher the tolerance of the species of low external water
      potentials. The mechanisms that integrate the relationship between plasma solute
      concentration and handling of urea by the kidneys are not known.

PMID- 9172373
TI  - Development of a radioactive protein A-based assay for analysis of surface
      protein expression in gram-positive bacteria.
AB  - This paper describes an immunochemical method which uses radioactive protein A
      for the detection and analysis of streptococcal M6 protein epitopes on the
      surface of recombinant Streptococcus gordonii. With this assay, recombinant S.
      gordonii cells expressing a portion of the M6 protein on their surfaces show a 75
      fold increase in bound radioactivity over cells of the control S. gordonii
      parental strain. Furthermore, use of the assay to monitor the amount of M6
      protein present on the surface of the S. gordonii recombinant during growth in
      culture demonstrated that expression is highest at late log phase, with the
      protein being sloughed off during stationary phase. This simple assay allows
      analysis of surface protein without any protein purification or sophisticated
      instrumentation. As such, it should be broadly applicable to following the
      expression of most surface-accessible bacterial proteins.

PMID- 9172372
TI  - Characterization of recombinant glutamine synthetase from the hyperthermophilic
      archaeon Pyrococcus sp. strain KOD1.
AB  - The glnA gene encoding glutamine synthetase was cloned from the hyperthermophilic
      archaeon Pyrococcus sp. strain KOD1, and its nucleotide sequence was determined.
      The glnA gene was expressed in Escherichia coli ME8459 (glnA mutant strain), and
      the protein was purified to homogeneity and shown to be functional in a
      dodecameric from (637,000 Da), exhibiting both transferase and synthetase
      activities. However, kinetic studies indicated that the enzyme possessed low
      biosynthetic activity, suggesting that the reaction was biased towards glutamate
      production. The optimum temperature for both activities was 60 degrees C, which
      was lower than the optimal growth temperature of KOD1. Recombinant KOD1 GlnA
      exhibited different optimum pHs depending on the reaction employed (pH 7.8 for
      the synthetase reaction and pH 7.2 for the transferase reaction). Of the various
      nucleoside triphosphates tested, GTP as well as ATP was involved in the
      synthetase reaction.

PMID- 9172375
TI  - Propranolol blocks the stimulatory effects of naloxone on ventilation and oxygen
      consumption in hamsters.
AB  - The purposes of these studies were: 1) to determine the effects of various doses
      of propranolol, a nonspecific beta-adrenergic antagonist, on ventilation, oxygen
      consumption, and body temperature in hamsters, and 2) to test the hypothesis that
      in hamsters the stimulatory effects of naloxone, an opioid receptor antagonist,
      on ventilation and oxygen consumption occur, at least in part, through the
      release of catecholamines that act via beta-adrenergic receptors. Propranolol, a
      non-specific beta adrenergic receptor antagonist, at a 20 mg/kg depressed body
      temperature, oxygen consumption, tidal volume, and ventilation relative to
      saline. The lower dose of 10 mg/kg had only transitory effects on tidal volume at
      60 min and ventilation at 30 min post-injection-Naloxone (1 mg/kg) relative to
      saline stimulated ventilation and oxygen consumption. These effects were blocked
      by propranolol pretreatment. The results of these experiments demonstrate that in
      the hamster, 1) body temperature, oxygen consumption, and ventilation appear to
      be modulated by beta-adrenergic receptors, and 2) the stimulatory effects of
      naloxone on oxygen consumption and ventilation may occur through the interaction
      of endogenous opioids and beta-adrenergic receptor systems.

PMID- 9172376
TI  - Optical recording of neural signals evoked by greater superficial petrosal nerve
      stimulation in rat.
AB  - Electrical responses to greater superficial petrosal (GSP) nerve stimulation in a
      rat geniculate ganglion (GG) preparation were assessed by simultaneous multi-site
      optical recording. The GG/GSP nerve preparations were dissected out and were
      stained with a voltage-sensitive dye (RH155). Application of depolarizing square
      pulses to the GSP nerve fibers using a suction electrode evoked optical
      (absorbance) signals that were recorded simultaneously from many contiguous
      regions using a 24 x 24 photodiode matrix array with 448 active elements. Those
      optical signals were observed along the left half area of the GSP nerve. As the
      distance from the site of stimulation increased, the optical signals appeared to
      conduct with increasing time-delay. From the relationship between the peak
      latency and distance, the conduction velocity was estimated to be about 0.4 m/s.
      Tetraethylammonium affected the duration of the optical signals, and the signals
      disappeared in solutions containing tetrodotoxin (TTX) or in Na(+)-deficient
      solutions. The optical signals evoked by the GSP nerve stimulation are considered
      to be due to the action potentials propagating along the GSP of unmyelinated
      axons.

PMID- 9172377
TI  - Limitation of dietary copper and zinc decreases superoxide dismutase activity in
      the onion fly, Delia antiqua.
AB  - Larvae of the onion fly, Delia antiqua, have lower superoxide dismutase (SOD)
      activity when they are fed a defined synthetic diet that contains no copper or
      zinc. SOD activity was rapidly recovered when these larvae were fed onion bulbs.
      Addition of copper and zinc to the synthetic diet also led to the recovery of SOD
      activity. Results of an immunoblotting analysis using anti-D. antiqua CuZnSOD
      mouse monoclonal antibody suggest that this alteration of SOD activity is
      dependent on the amount of CuZnSOD.

PMID- 9172378
TI  - Expanding forces in aqueous outflow pathways of a nonaccommodating mammal: an
      approach via comparative dynamic morphology.
AB  - Six dog eyes were fixed by intracameral perfusion of fixative at pressures of 0,
      5, 10, 15, 20, and 25 cm of water. Eight dog eyes were fixed after the injection
      in both ocular chambers of a number of cholinergic agents, either singly or in
      combination. Under the effect of miotics and under increased ocular pressure, the
      aqueous pathways expand. An analysis of the forces involved in expansion of the
      exit pathways reveals the primary role of the detached ciliary body in
      nonaccommodating mammals. Two mechanisms appear to have been conserved in dogs
      and humans throughout evolution. The first is an active mechanism: the opening of
      the trabecular meshwork as a consequence of the combined action of the ciliary
      muscle and the iris and its insertion ligaments-the uveoscleral trabeculate-in
      dogs, and the longitudinal portion of the ciliary muscle and scleral spur in
      humans. The second is a passive mechanism: the infundibular arrangement of the
      drainage structures assisted by the traction on the zonular ligament of the lens,
      which responds to an increase in pressure in the anterior chamber by widening the
      pathways, thus favoring outflow.

PMID- 9172379
TI  - Inactivity changed fiber type proportion and capillary supply in cat muscle.
AB  - The effect of different levels of activity on fiber types, capillaries and
      enzymes of gastrocnemius and soleus muscles was studied in two groups of cats.
      The first group was successfully kept in a large room, exercised on a treadmill
      15 min daily 5 days per week and kept in individual small cages. Each period
      lasted 6 weeks. A muscle biopsy was taken after each period. The second group was
      formed by cats that were caged for over 20 months. In the group caged for over 20
      months, gastrocnemius muscle showed higher IIB and lower I fiber type proportion.
      Fiber cross-sectional area was not different in any condition. All capillary
      measurements were significantly lower in gastrocnemius muscle of long-term caged
      cats, and capillaries per mm2 were lower in soleus muscle of these cats. Exercise
      increased capillary/fiber in soleus muscle but subsequent caging did not reduced
      it. In soleus muscle, beta-hydroxy-acyl-CoA dehydrogenase levels decreased after
      the cage period and hexokinase levels increased after the exercise and decreased
      after the cage period. In conclusion, different levels of activity for short time
      produced enzyme changes in soleus muscle, whereas long-term inactivity changed
      fiber type proportion in gastrocnemius muscle and reduced capillary supply.

PMID- 9172380
TI  - Modulation of the GABAA response in rat ventromedial hypothalamic neurons by
      pregnanolone.
AB  - The effects of 5 beta,3 alpha-pregnanolone (PGN) on gamma-aminobutyric acid
      (GABA)-induced Cl- current in acutely dissociated rat ventromedial hypothalamic
      neurons were investigated using the nystatin perforated patch recording mode
      under voltage-clamp conditions. The PGN at concentrations between 10(-7) and 10(
      5) M evoked an inward current at a holding potential (VH) of -40 mV. The reversal
      potential of the PGN-induced current was close to the equilibrium potential of Cl
      . PGN potentiated the GABA-induced Cl- current in a concentration-dependent
      manner. The facilitatory effect was long lasting and disappeared slowly after
      being washed out. The effect of PGN on the GABA response was also affected by the
      pretreatment time of PGN. PGN shifted the concentration-response relationship for
      GABA to the left with a suppression of the maximal response to GABA, resulting
      from the rapid inactivation of the GABA response during PGN treatment.
      Facilitatory interactions were found to exist among GABA, pentobarbital,
      diazepam, and PGN. Three other PGN isomers were also effective in facilitating
      the GABA response. However, the isomers containing the 3 alpha-hydroxy
      configurations potentiated the GABA response much more potently and only these
      isomers exhibited inward currents themselves.

PMID- 9172381
TI  - Short-term cold-exposure does not improve insulin sensitivity in rats.
AB  - Effects of noradrenergic activation induced by short-term cold-exposure (7 days
      at 4 degrees C) on whole-body glucose utilization and tissue glucose uptake were
      investigated in rats. Measurements were realized on anesthetized normothermic
      animals at four different levels of insulinemia, within physiological range,
      allowing calculation of insulin sensitivity and responsiveness. Whole-body
      glucose utilization increased as a logarithmic function of insulinemias, and was
      always higher in cold-exposed than in control rats. However, neither insulin
      sensitivity nor responsiveness, literally, appeared different between the two
      groups. In the diaphragm, the only studied working muscle, glucose uptake was
      largely higher than in restin muscles. At basal insulin concentration, glucose
      uptake was higher in cold-exposed than in control rats and increased in the two
      groups with insulinemia. Among resting muscles, glucose uptake was increased by
      previous cold exposure in gastrocnemius, soleus, and tibialis. However, insulin
      sensitivity and responsiveness were found augmented only in the two former. In
      interscapular brown adipose tissue, glucose uptake was largely higher in cold
      exposed than in control rats, but no difference could be evidenced in insulin
      sensitivity or responsiveness. In white adipose tissues, glucose uptake increased
      with insulinemia. Insulin responsiveness and sensitivity were higher only in the
      retroperitoneal depot.

PMID- 9172382
TI  - Kinetics of pancreatic exocrine secretion and plasma gut regulatory peptide
      release in response to feeding in preruminant and ruminant calves.
AB  - Pancreatic exocrine secretion and plasma cholecystokinin, gastrin, secretin, and
      somatostatin concentrations were examined in relation to feeding in 70- to 120
      day-old preruminant and ruminant calves. The apparatus used was designed to
      immediately re-infuse the animal's own pancreatic juice and to carry out accurate
      measurements of the juice flow in real time and to take samples. In the
      preruminants, pancreatic juice, protein, and trypsin flows increased from 45 min
      before and until 15 min after the meal and decreased sharply thereafter over a
      period of 30 min. while protein and trypsin concentrations peaked after feeding.
      A significant increase in plasma gastrin and cholecystokinin (CCK), a fall in
      secretin and no change in somatostatin were observed after milk ingestion. By
      contrast, in the ruminants, feeding had no effect on the pancreatic secretion and
      on the plasma concentrations of these peptides. Similar and simultaneous patterns
      of juice flow and secretin, as well as of protein and trypsin concentrations, CCK
      and gastrin, could support the hypothesis that these gut regulatory peptides play
      a significant role in the regulation of the pancreatic function. In preruminant
      calves, the existence of cephalic, gastric and intestinal phases is discussed. In
      the ruminants, that of the ruminal phase is questionable.

PMID- 9172383
TI  - Protective effect of diltiazem on myocardial ischemic injury associated with .OH
      generation.
AB  - We examined the protective effect of diltiazem, a calcium antagonist, on
      myocardial ischemic injury associated with generation of hydroxyl free radicals
      (.OH). Salicylic acid in Ringer's solution (0.5 nmol.microliter-1.min-1) was
      infused directly through a microdialysis probe to detect the generation of .OH as
      reflected by the formation of 2,3-dihydroxybenzoic acid (DHBA) in the myocardium.
      Cardiac dialysate was assayed for 2,3-DHBA by a high-performance liquid
      chromatographic-electrochemical (HPLC-EC) procedure. The heart was subjected to
      myocardial ischemia for 15 min by occlusion of left anterior descending artery
      (LAD). The presence of .OH was indicated in the ischemic reperfused rat heart.
      However, when heart was reperfused, the elevation of 2,3-DHBA by 15-min ischemia
      was not observed in the ischemic zone following systemic administration of
      diltiazem (100 micrograms.min-1.kg-1), a calcium antagonist. When corresponding
      experiments were performed with allopurinol (10 mg.kg-1) administration of i.v.
      injection, the elevation of 2,3-DHBA was not observed. These results suggest that
      diltiazem may suppress the .OH generation from xanthine-xanthine oxidase system
      by ischemia-reperfusion.

PMID- 9172384
TI  - "Compensatory" organic osmolytes in high osmolarity and dehydration stresses:
      history and perspectives.
AB  - As stated in the conclusion, "life is a thing of macromolecular cohesion in salty
      water." This brief historical overview shows that "compensatory" organic
      osmolytes take an essential place in this cohesion. It reviews the major steps of
      the study of these compounds over more than 100 years, from the early beginnings
      of 1885 until now, showing some of its fascinating developments and ending on the
      idea that the most fascinating is still to come. This study can be taken as an
      example of the richness of the comparative approach.

PMID- 9172385
TI  - Mitogen-activated protein kinase cascades and the signaling of hyperosmotic
      stress to immediate early genes.
AB  - Among prokaryotes and lower eukaryotes, the threat of exposure to hyperosmotic
      stress is ubiquitous. Among higher eukaryotes, in contrast, only specific tissues
      are routinely exposed to marked hypertonicity. The mammalian renal medulla, the
      prototypical example, is continually subjected to an elevated solute
      concentration as a consequence of the renal concentrating mechanism. Until
      recently, the investigative focus has concerned the effects of diverse solutes on
      the regulation of genes essential for the adaptive accumulation of osmotically
      active organic solutes. Recent and sweeping developments elucidating the
      molecular mechanisms underlying stress signaling to the nucleus have focused
      interest on earlier events in the response to hyperosmotic stress. Such events
      include the transcriptional activation and post-translational modification of
      transcriptional activating proteins, a large subset of which represent the
      protein products of so-called immediate early genes. This review highlights
      developments in the understanding of stress signaling in general and hypertonic
      stress signaling in particular in both yeast and higher eukaryotic models. The
      relationship between hyperosmotic stress signaling and the transcription and
      activation of immediate-early gene transcription factors is explored.

PMID- 9172386
TI  - Kidney cell survival in high tonicity.
AB  - The kidney medulla of mammals undergoes large changes in tonicity in parallel
      with the tonicity of the final urine that emerges from the kidney at the tip of
      the medulla. When the medulla is hypertonic, its cells accumulate the compatible
      osmolytes myo-inositol, betaine, taurine, sorbitol and glycerophosphorylcholine.
      The mechanisms by which the compatible osmolytes are accumulated have been
      explored extensively in kidney-derived cells in culture. Myo-inositol, betaine
      and taurine are accumulated by increased activity of specific sodium-coupled
      transporters, sorbitol by increased synthesis of aldose reductase that catalyses
      the synthesis of sorbitol from glucose. Glycerophosphorylcholine accumulates
      primarily because its degradation is reduced in cells in hypertonic medium. cDNAs
      for the cotransporters and for aldose reductase have been cloned and used to
      establish that hypertonicity increases the transcription of the genes for the
      cotransporters for myo-inositol, betaine and for aldose reductase. The region 5'
      to the promoter of the gene for the betaine cotransporter and for aldose
      reductase confer osmotic responsiveness to a heterologous promoter. The 12-bp
      sequence responsible for the transcriptional response to hypertonicity has been
      identified in the 5' region of the gene for the betaine cotransporter.

PMID- 9172387
TI  - Effects of compensatory solutes on DNA and chromatin structural organization in
      solution.
AB  - We investigated the effect of glycine and other osmotic effectors on DNA and
      chromatin precipitation by mono-, di- and multivalent cations and histone H1. The
      addition of these compounds drastically reduces the precipitation effects with an
      efficiency in the order taurine > glycine > proline and sorbitol > inositol >
      betaine. Aminocarboxylic acids with increasing distance between the charged C-
      and N-terminal groups displayed enhanced efficiency in the protection effect
      against DNA precipitation. We interpreted these observations on the basis of
      Manning's counterion condensation theory, taking into account the increase in
      dielectric constant upon osmotic effector addition. 23Na-NMR was used to evidence
      sodium counterions release as a result of this increase in dielectric constant.

PMID- 9172388
TI  - Organic solutes in freezing tolerance.
AB  - The accumulation of high levels of low-molecular-weight solutes (polyhydric
      alcohols, saccharides) provides cryoprotection to freeze-tolerant animals by
      minimizing, via colligative effects, the percentage of body water converted to
      extracellular ice and the extent of cell volume reduction. Many freeze-tolerant
      insects accumulate high levels of polyols during autumn cold hardening, whereas
      freeze-tolerant frogs respond to ice formation in peripheral tissues by
      synthesizing large amounts of glucose in the liver and rapidly distributing the
      sugar throughout the body. Seasonal patterns of enzymatic change occur in cold
      hardy insects; activities associated with cryoprotectant synthesis rise in the
      fall, whereas enzymes associated with polyol degradation dominate in the spring.
      Enzyme profiles also revealed the route of glycerol degradation via polyol
      dehydrogenase and the novel enzyme, glyceraldehyde kinase. Proton magnetic
      resonance imaging of freezing and thawing in whole frogs showed a new adaptive
      effect of the very high glucose levels in core organs; during thawing, organs
      such as liver and heart melted first, allowing recovery of their vital functions
      to begin while the rest of the frog thawed. New studies have examined signal
      transduction in the stimulation of glucose production by wood frog liver,
      revealing the key role of beta-adrenergic receptors and cAMP-mediated activation
      of glycogenolysis for cryoprotectant synthesis. The seasonal elevation of plasma
      membrane glucose transporters was also shown to be key to cryoprotectant
      distribution during freezing. Other new work has shown that frog freeze tolerance
      probably grew out of preexisting mechanisms of amphibian dehydration tolerance
      and that both freeze-tolerant and -intolerant frogs show a hyperglycemic response
      to desiccation at 5 degrees C.

PMID- 9172389
TI  - Functional characterisation of Eskimo dog hemoglobin: I. Interaction of Cl- and
      2,3-DPG and its importance to oxygen unloading at low temperature.
AB  - The oxygen binding properties of hemoglobin and some hematological parameters in
      Eskimo dogs (belonging to Canis lupus familiaris) in Ilulissat/Jacobshavn,
      Greenland were analysed. The average [2,3-DPG] and [Hb] (n = 16) were 3.14 +/-
      0.34 mmol l-1 blood and 9.53 +/- 0.65 g dl-1 (1.49 mmol l-1), respectively,
      giving a stoichiometric ratio of 2.11 mol 2,3-DPG/mol Hb. Oxygen binding analysis
      carried out on hemolysate in HEPES buffer at 20 and 37 degrees C revealed a high
      oxygen affinity (1.2 mmHg at pH 7.4, 20 degrees C) in the desalted condition,
      which decreased markedly in the presence of chloride and 2,3-DPG. A low apparent
      equilibrium constant for the binding of 2,3-DPG (1.0 x 10(-5) mol l-1) was found
      at pH 7.2 and 20 degrees C in the absence of chloride. Moreover, we show that
      chloride ions have an additive effect on oxygen affinity in the concentration
      range 10-300 mmol l-1 in the presence of 3 mmol l-1 2,3-DPG at low pH and
      temperature (pH < 7.4 and 20 degrees C). This feature may be of physiological
      importance to oxygen unloading under acidotic conditions when tissue temperature
      is low. Thermodynamic analysis reveal that in the presence of 3 mmol l-1 2,3-DPG
      and 100 mmol l-1 chloride, the Eskimo dog hemoglobin exhibits a low heat of
      oxygenation, which places this animal close to arctic ruminants with respect to
      the influence of temperature on oxygen binding in vivo.

PMID- 9172390
TI  - Functional characterisation of Eskimo dog hemoglobin: II. The interplay of HCO(3)
      and Cl-.
AB  - Hemoglobin (Hb) from the Eskimo dog (belonging to Canis lupus familiaris) showed
      similar Bohr effect (delta log P50/delta pH) to human HbA in the presence of 100
      mmol l-1 NaCl at 20 degrees C. The presence of 7% carbon dioxide in the desalted
      condition caused a positive (reversed) Bohr effect in the pH range 7.1-7.5 on
      Eskimo dog Hb, whereas in human HbA there was no Bohr effect within this pH
      range. A positive Bohr effect on Eskimo dog Hb in this condition was also
      observed at 37 degrees C. This could indicate differences in the pK values of the
      amino terminal residues of the two hemoglobins, with possible pH-dependent
      binding of both bicarbonate (HCO(3)-) and carbamate. Analysis of the effect of
      CO2 on oxygen affinity of Eskimo dog Hb in the pH range 6.7-7.6 in the presence
      of chloride and/or 2,3-diphosphoglycerate (2,3-DPG) support this theory. Our
      results indicate a competition between HCO(3)- and Cl- in affecting oxygen
      binding. Thermodynamic analysis reveals that bicarbonate binding lowers the
      apparent heat of oxygenation in Eskimo dog Hb nearly as much as chloride does in
      the presence of 2,3-DPG at physiological pH. This safeguards an effective oxygen
      unloading at lowered red blood cell concentrations of chloride. Moreover, we show
      that the oxygen affinity at high O2 saturation is less dependent on temperature
      in the presence than in the absence of CO2-.

PMID- 9172391
TI  - Nonshivering thermogenesis in marsupials: absence of thermogenic response to beta
      3-adrenergic agonists.
AB  - The status of nonshivering thermogenesis (NST) in marsupials remains
      controversial. Although morphological studies have failed to find evidence for
      the presence of brown adipose tissue (BAT) in adults or juveniles of species from
      all extant families of marsupial, a number of studies have investigated the
      metabolic response of marsupials to noradrenaline (NA) and yielded conflicting
      results. In eutherian mammals, NA stimulates NST in BAT by acting on beta 3
      receptors, and in the experiments reported here we investigated the response of
      adult and juvenile brush tail possums (Trichosurus vulpecula), a Brazilian
      opossum (Monodelphis domestica), adult and juvenile red-necked (Bennett's)
      wallabies (Macropus rufogriseus) and the laboratory rat to selective beta 3
      agonists (ICI D7114 and BRL 35135) and to NA. Wallabies were tested with the beta
      3-agonists only. Although NA and both beta 3-agonists caused an 85% increase in
      oxygen consumption in rats, there was no significant effect on any of the
      marsupials. These results clearly indicate no beta 3-stimulated NST in these
      marsupials. All reports of metabolic responses to NA are from macropods, and a
      recent study demonstrates that NA and other alpha-adrenergic agonists stimulate
      thermogenesis in a small macropod, the bettong (Bettongia gaimardi), by acting on
      alpha 1-receptors. Thermogenic responses to NA seems to be restricted to
      macropods, showing the danger of characterising the response of any one marsupial
      species as being representative of marsupials as a group.

PMID- 9172392
TI  - Temperature effects on ion transport across the erythrocyte membrane of the frog
      Rana temporaria.
AB  - Unidirectional K+ and Na+ influxes in the frog erythrocytes incubated in Cl- or
      NO(3)- media with 2.7 mM K+ were measured using 86Rb and 22Na as tracers. K+
      influx was inhibited by 35-55% in the presence of 0.2-1.0 mM furosemide but it
      was unaffected by 0.1-0.2 mM bumetanide. Furosemide at a concentration of 0.5 mM
      had no effect on K+ loss from the frog red cells incubated in a nominally K(+)
      free medium. Together with our previous studies the data support the existence of
      K-Cl cotransport and the absence of Na-K-2Cl cotransport in the frog erythrocyte
      membrane. Cell cooling from 20 to 5 degrees C caused a decrease in K+ influx and
      K+ efflux via the K-Cl cotransporter (3.2- and 3.7-fold, respectively) giving an
      apparent energy of activation (EA) of about 60 kJ/mol and Q10 value of 2.5. Only
      small decline (approximately 30%) in the ouabain-sensitive K+ influx was found as
      temperature was changed from 20 to 5-10 degrees C. Low values of Q10
      (approximately 1.5) and EA (27.3 kJ/mol) were obtained for passive K+ influx in
      the frog erythrocytes (ouabain-insensitive in NO(3)- medium) at temperature
      within 5-20 degrees C. However, the temperature coefficients were greater for
      passive Na+ influx and passive K+ efflux (Q10 approximately 2.4-2.5 and EA
      approximately 56-58 kJ/mol). The temperature dependence of all ion transport
      components displayed discontinuities showing no changes at temperature between 5
      and 10 degrees C. Thus, cooling of the frog red cells is associated with a
      greater decrease of Na+ influx and K+ efflux than passive and active K+ influx.
      These data indicate that the preservation of a relative high activity of the Na,K
      pump during cell cooling and also the temperature-induced changes in the K-Cl
      cotransport activity and ion passive diffusion contribute to maintenance of ion
      concentration gradients in the frog erythrocytes at decreased temperature.

PMID- 9172393
TI  - A multimodal approach for diagnosing patients with acute promyelocytic leukaemia.
AB  - A practical and efficient multi-modal protocol for processing specimens for
      patients referred with a question of acute promyelocytic leukaemia (APL) is
      described. The initial analysis comprises haematological evaluation of the bone
      marrow and peripheral blood smears using Romanowsky-stained slides.
      Concomitantly, a sample is processed for direct preparation as well as 1- and 2
      day unstimulated cultures using conventional cytogenetic techniques.
      Communication between the cytogenetic and haematological laboratories is of
      critical importance so that the optimal conditions for culture (i.e. longer term
      versus unstimulated overnight and direct preparations) for the cytogenetic
      detection of chromosome rearrangements can be selected. The likelihood of
      detecting the characteristic translocation of APL, t(15;17), is enhanced in a
      longer term culture versus unstimulated overnight and direct preparations.
      Fluorescent in situ hybridization (FISH), utilized as an adjunct to GTG-banding,
      was found to be a powerful technique for detecting the t(15;17), especially where
      the GTG-banded preparation was of suboptimal quality. Results of five recent
      representative cases of APL are described to illustrate a practical approach
      which can be adapted by any clinical pathology laboratory.

PMID- 9172394
TI  - Mitotic effects of the aqueous leaf extract of Cymbopogon citratus in Allium cepa
      root tips.
AB  - Aqueous extracts of the lemon grass, Cymbopogon citratus, were used to clear the
      malaria parasite in infected mice, although they died some days later. Allium
      cepa roots grown in aqueous extracts from 3, 6, 12 and 20 g of chopped leaves for
      1, 3, and 6 h, showed some mitotic abnormalities including c-mitotic and
      mitodepressive effects. The abnormalities were not peculiar to any concentration
      or duration of extract treatment. The highest frequency of affected cells was
      0.75% in the treatment with the 20 g concentration, but the 3 h treatment group
      had the greatest variety of effects. The mitodepressive effect of the extract
      increased significantly with concentration and time, and persisted even after 24
      h in tap water. The chromosomal effects of the extract occur at a very low
      frequency but the mitodepressive effects may have implications for man.

PMID- 9172395
TI  - Structure and amount of genetic variation at minisatellite loci within the
      subspecies complex of Phoca vitulina (the harbour seal).
AB  - The structure and amount of genetic variation within and between three subspecies
      of the harbour seal Phoca vitulina was assessed by multilocus DNA fingerprinting.
      Bandsharing similarity indicates that the subspecies Phoca vitulina richardsi
      (Alaska, East Pacific) is clearly separated from the other two subspecies, Phoca
      vitulina concolor (Sable Island, West Atlantic) and Phoca vitulina vitulina
      (North Sea, East Atlantic). The subspecies also differ significantly in the
      estimated amount of heterozygosity. Phoca vitulina richardsi has by far the
      highest amount of genetic variation, whereas P. vitulina vitulina has very low
      levels of genetic variation. Within the subspecies P. vitulina vitulina,
      especially the Wadden Sea population is depauperate of genetic variation. The
      findings are discussed in a historical, biogeographical and a conservation
      biological context.

PMID- 9172396
TI  - Detection of Escherichia coli O157:H7 and other verocytotoxin-producing E. coli
      (VTEC) in food.

PMID- 9172397
TI  - Pril-ampicillin-dextrin-ethanol agar for the isolation and quantification of
      Aeromonas spp. from polluted environmental waters.
AB  - Several selective media were evaluated for their suitability for the isolation
      and quantification of mesophilic Aeromonas species from naturally polluted
      samples. Satisfactory recoveries were obtained with most of them but only when
      densities of background microflora were low. When analysed samples were from
      highly polluted waters, results were inconsistent because they did not give
      quantitative recovery of mesophilic aeromonads or they did not permit ready
      differentiation of Aeromonas species from the competitive bacteria. A new medium
      was developed on the basis of the combination of some positive aspects of several
      published media, pril-ampicillin-dextrin-ethanol (PADE) agar. The medium employs
      dextrin (Merck 3006) as a fermentable carbohydrate and pril, ampicillin and
      ethanol as inhibitory substances. Recovery on PADE agar from suspensions of 15
      tested strains of Aeromonas prepared from pure cultures was excellent. The
      confirmation rate of typical colonies designated Aeromonas spp. isolated from
      polluted samples exceeded 90%. Recoveries of stressed aeromonad strains on both
      PADE agar and a non-selective medium (TSA) did not show any significant
      difference (P > 0.05). PADE agar was more reliable for quantitative recovery of
      mesophilic aeromonads than the other selective media because of its
      characteristics: (i) inhibition of the swarming of Proteus, (ii) good reduction
      of the background, (iii) inhibition of the over growth of Klebsiella spp., (iv)
      absence of NaCl makes it unfavourable for the growth of halophilic vibrios, (v)
      combination of two pH indicators permitted a very easy differentiation between
      Aeromonas colonies and the competitive microflora. The medium can also be used
      for isolation of aeromonads from various sources by membrane filtration.

PMID- 9172398
TI  - Expanded models for the non-thermal inactivation of Listeria monocytogenes.
AB  - Previously developed four-variable response surface models for describing the
      effects of temperature, pH/lactic acid, sodium chloride and sodium nitrite on the
      time to achieve a 4-log, non-thermal inactivation (t4D) of Listeria monocytogenes
      in aerobic, acidic environments were expanded to five-variable models that
      distinguish the effects of pH and acidulant concentration. A total of 18 new
      variable combinations were evaluated and the inactivation kinetics data appended
      onto a consolidation of two data sets from earlier studies. The consolidated data
      set, which included 315 inactivation curves representing 209 unique combinations
      of the five variables, was analysed by response surface analysis. The quadratic
      model without backward elimination regression was selected for further
      evaluation. Three additional quadratic models were generated using the
      concentrations of undissociated lactic and/or nitrous acids as variables in place
      of percentage lactic acid and sodium nitrite concentration. Comparison of
      predicted t4D values against literature values for various food systems indicated
      that the models provide reasonable initial estimates of the inactivation of L.
      monocytogenes. The models based on the concentration of undissociated lactic and
      nitrous acids support the hypothesis that antimicrobial activity is associated
      with this form of the compounds. Evaluation of several examples suggests that
      these models may be useful for predicting the equivalent of the compounds'
      "minimal inhibitory concentrations' for accelerating inactivation under various
      conditions.

PMID- 9172399
TI  - Characterization of strains of Leuconostoc mesenteroides by analysis of soluble
      whole-cell protein pattern, DNA fingerprinting and restriction of ribosomal DNA.
AB  - Of 215 leuconostocs isolated from field grass, natural whey cultures and water
      buffalo milk, 178 were identified as Leuconostoc mesenteroides ssp. mesenteroides
      while 37 strains could not be identified. Biochemical characterization allowed
      seven groups to be defined. Representative strains of each group and different
      habitat and nine reference strains were selected for further analyses. Protein
      profiles appeared suitable for species discrimination, but did not differentiate
      between the three subspecies of Leuc. mesenteroides. The technique also showed
      some differences among equivocal strains. DNA fingerprinting for most strains of
      Leuc. mesenteroides ssp. mesenteroides examined showed a different restriction
      pattern from that of the type strain. Ribotyping was not useful for
      discriminating species and subspecies of the genus Leuconostoc: Leuc.
      mesenteroides ssp. mesenteroides and ssp. dextranicum showed the same ribopattern
      as Leuc. lactis while Leuc. mesenteroides ssp. cremoris exhibited a pattern
      distinct from all the other species examined. On the basis of ARDRA-PCR, two main
      groups could be distinguished: the larger group included Leuc. mesenteroides,
      Leuc. lactis, Leuc. pseudomesenteroides and some unidentifiable strains; the
      second one included Leuc. citreum, Leuc. fallax, Weissella paramesenteroides and
      some unidentified strains.

PMID- 9172400
TI  - Isolation and identification of Burkholderia pseudomallei from soil using
      selective culture techniques and the polymerase chain reaction.
AB  - An environmental soil survey to detect Burkholderia pseudomallei was performed
      during the dry and wet seasons in Darwin, Northern Territory, Australia. Soil was
      sampled at regular intervals during a 15-month period at different depths from
      areas which were representative of the local, soil environment. Selective culture
      techniques using Ashdown's and Galimand and Dodin's methods and the polymerase
      chain reaction (PCR) using specific 16S rRNA primers were used to detect and
      identify the organism and determine its distribution within the soil stratum over
      the change in seasons. Results showed that Ashdown's method gave higher isolation
      rates in the dry season, and Galimand and Dodin's method gave higher isolation
      rates during the wet season. PCR of the soil enrichment proved to be a more
      sensitive method than culture and was also a useful confirmatory test in
      determining the identification of isolates where biochemical tests gave
      inconsistent results. The PCR primers were specific and able to detect 10(1) cfu
      g-1 soil and 10(4) cfu g-1 of soil using Ashdown's enrichment broth and Galimand
      and Dodin's broth, respectively. Overall the isolation of B. pseudomallei was
      greatest during the dry season and at the higher and lower soil depths, which is
      contradictory to epidemiological evidence that melioidosis occurs primarily
      during the wet season among patients exposed to contaminated surface soil and
      water.

PMID- 9172401
TI  - Isolation and characterization of coliforms from glacial ice and water in
      Canada's High Arctic.
AB  - Ellesmere Island is the northern most member of the Canadian Arctic Archipelago
      with over one-third of the land mass covered by ice. A joint services expedition
      to the island's Blue Mountains offered a unique opportunity for microbiological
      studies of resident bacteria in an environment uninhabited by man. Over 100
      samples of water and ice were collected from stream, lake and glacier and the
      filtrate cultured under canvas. Bacterial growth was harvested onto swabs for
      transport back to the UK and 50 coliforms chosen at random for identification and
      antibiotic susceptibility testing. Most of the glacial strains were capsulated,
      pigmented and some over 2000 years old. Genera such as Serratia, Enterobacter,
      Klebsiella and Yersinia were found; speciation was inconclusive and some
      organisms remain unidentified. Ampicillin resistance was evident in 80% of water
      isolates as opposed to 30% of the glacial organisms, but the isolates were
      generally exquisitely susceptible to antibiotics. The facility for ampicillin
      resistance did not appear to be transferable. Plasmid DNA was found in 33% of the
      glacial organisms and over 50% of the water isolates. Similar profiles were
      identified within and apparently between species and required plasmid restriction
      analysis to help establish identity. Plasmid-free Serratia spp. were subjected to
      genomic fingerprinting. Indistinguishable patterns were found within sets of
      isolates both widely spaced by distance and collection date and it was postulated
      that coliforms able to survive an Arctic environment had spread extensively
      throughout the expedition area. In conclusion, this study contributes towards
      knowledge of naturally occurring antibiotic resistance, confirms the presence of
      plasmids and genotypic data provided evidence that potentially ancient organisms
      from glaciers can be cultured from water samples significantly distant.

PMID- 9172402
TI  - The effects of growth dynamics upon pH gradient formation within and around
      subsurface colonies of Salmonella typhimurium.
AB  - pH measurements made in and around submerged colonies of Salmonella typhimurium
      grown within a model gelatin gel system using pH-sensitive micro- and
      macroelectrodes indicated some pH heterogeneity occurring in and around the
      bacterial colony. Inoculation density, initial pH and glucose concentration were
      all found to influence colony diameter and metabolism of Salmonella colonies.
      Colony growth in the presence of glucose, at pH 7.0 with an inoculation density
      of 1 cell ml-1 led to a pH fall of 1-2 pH units after 2 d. At pH 5.0, with
      glucose, colony growth rates were much slower than at pH 7.0, and the pH change
      varied by less than one pH unit often becoming alkaline. In the absence of
      glucose, only small pH changes were observed within the medium, although growth
      rates were similar to those in glucose-containing media. At the higher
      inoculation density (ca 1000 cells ml-1), isolated pH changes were not observed.
      Morphological changes, such as the production of annular rings, were noted in
      stationary phase colonies as was alkali production in colonies. These results are
      discussed in relation to observations with surface colonies.

PMID- 9172403
TI  - Glycerol and other fermentation products of apiculate wine yeasts.
AB  - Ninety-six strains of apiculate wine yeasts were studied for their ability to
      produce glycerol, acetaldehyde, ethyl acetate, sulphur dioxide and hydrogen
      sulphide in synthetic medium. Hanseniaspora guilliermondii produced smaller
      quantities of glycerol, acetaldehyde and hydrogen sulphide than Kloeckera
      apiculata, whereas the production of ethyl acetate and sulphur dioxide was found
      to be similar. Strains characterized by different capacities and properties were
      found for both species. The existence of apiculate strains differing in secondary
      compound production is of technological interest, as these yeasts constitute
      potential flavour producers. Selected strains of apiculate yeasts might favour an
      enhanced flavour formation and yield desirable characteristics to the final
      product.

PMID- 9172404
TI  - Monoclonal antibody detection of Clostridium microcolonies directly on membrane
      used for milk filtration.
AB  - The normal procedure for bacterial colony detection requires a nitrocellulose
      transfer step after membrane filtration and culture to prevent the development of
      a high background during the immunodetection. In this paper, we describe a
      modification of the basic protocol that omits the transfer step and reduces the
      risk of background. Previous observations indicated that interactions between
      milk components (principally cream) and membrane are responsible for the high non
      specific staining observed. Experiments were performed to remove lipid components
      or to block the membrane binding sites before milk filtration. Samples of milks
      of different origin (collected at different times of the year) and different
      membranes were tested. The results obtained showed that removing lipids did not
      significantly improve the test but, on the contrary, led to an antigen diffusion.
      Incubation of the membrane in 0.1% (w/v) of Tween 20 in phosphate-buffered saline
      before milk filtration prevented non-specific binding, and allowed performance of
      the detection without any noticeable background.

PMID- 9172405
TI  - Anti-smooth muscle antibody in clinical human and experimental animal Mycoplasma
      pneumoniae infection.
AB  - Autoantibody formation is possibly integral to the development of non-respiratory
      manifestations of acute Mycoplasma pneumoniae infection. We sought to confirm the
      occurrence of smooth muscle antibodies (SMA) in humans with acute Myc. pneumoniae
      respiratory infection and furthermore to assess whether similar autoantibodies
      would develop in a hamster model of respiratory infection. Paired sera from 21
      patients with acute infection were assayed for SMA by immunofluorescence on mouse
      kidney/stomach substrates. The frequency of SMA was then determined for 52
      paediatric patients with acute Myc. pneumoniae infection and 16 controls, and for
      sera from a hamster model of infection. Five of 21 paired sera had an increment
      in SMA between acute and convalescent specimens. At a screening dilution of 1:40,
      18/52 infected and 0/16 controls had positive sera (P = 0.003); positive
      specimens demonstrated IgG rather than IgM SMA. In the hamster model of Myc.
      pneumoniae respiratory infection, significant IgG SMA increases occurred in 7/19
      infections but not in 11 controls (P = 0.02). Immunoblotting did not identify
      actin as the substrate for SMA. Smooth muscle antibody increases are found in a
      significant minority of Myc. pneumoniae-infected humans and hamsters. A role for
      SMA in the pathogenesis of Myc. pneumoniae infection remains to be defined.

PMID- 9172406
TI  - Changes with growth rate in the membrane lipid composition of and amino acid
      utilization by continuous cultures of Campylobacter jejuni.
AB  - Methods and media (defined and complex) are described which permit studies
      designed to determine the influence of single environmental factors on the
      survival and virulence of Campylobacter jejuni. The effect of growth rate on
      selected physiological traits (amino acid utilization, membrane lipid
      composition, motility, cell morphology) was studied in continuous culture. In
      both media, growth was at the expense of amino acid (serine, aspartate, glutamate
      and proline) catabolism. Slow growth in the complex medium shifted amino acid
      utilization from more (serine and aspartate) to less preferred substrates
      (glutamate, proline and possibly amino acids from the proteolysis of peptones).
      Low growth rates promoted the conversion of unsaturated 11-octadecenoic acid
      substituted phosphatidyl ethanolamines to corresponding 11-methylene substituted
      species, a feature correlated with stationary phase and exposure to environmental
      stress in other organisms. During continuous growth, cells lost motility although
      they still possessed flagella. Slow growth resulted in longer cells. Future
      studies will investigate the independent effects of nutrient stress and growth
      rate on the virulence and persistence of cells.

PMID- 9172407
TI  - Prevalence of Listeria sp. in droppings from urban rooks (Corvus frugilegus).
AB  - Droppings from 112 urban rooks (Corvus frugilegus) were cultured for the presence
      of Listeria sp. Overall, 46% of rooks sampled harboured one or more Listeria
      species. Of all birds examined, 33%, 24% and 8%, respectively, were infected with
      Listeria monocytogenes, Listeria innocua and Listeria seeligeri. Differentiation
      of L. monocytogenes and L. seeligeri carried out by several phenotypic typing
      methods proved the diversity of strains and the major role of rooks which widely
      contribute to spreading this bacteria in our environment. The results also
      suggest that the ability to recover specific Listeria strains from the same
      sample is at least partially dependent on the methodology. These findings
      reinforce the need for strain-specific typing of multiple L. monocytogenes
      isolates from the same sample.

PMID- 9172408
TI  - Selective isolation of Aspergillus niger mutants with enhanced glucose oxidase
      production.
AB  - After mutagenization and selection, mutant Aspergillus niger strains resistant to
      certain agents were obtained. Seven of the mutants showed increased extracellular
      glucose oxidase (GOD), the level for individual cases ranged widely from 8.8 to
      over 138.5% in comparison with the parental strain. Studies of the relationship
      between method of selection and frequency of mutation showed that the highest
      frequency of positive mutations (15.8% and 17.3%) was obtained from mutants
      resistant to ethidium bromide (1 mmol l-1 and sodium gluconate (45%),
      respectively. The time course of growth and enzyme production by the most active
      mutant AM-11 showed intra- and extracellular GOD activities to have increased
      about 2.2- and 2.4-fold, respectively, compared with the parental strain.

PMID- 9172409
TI  - Microbial contamination of hydrogel contact lenses.
AB  - Bacterial contamination of contact lenses (CLs) may contribute to CL-related
      corneal infection and inflammation. This study reports CL biota over time during
      daily and extended wear. Microbial contamination of a 58% water, ionic hydrogel
      CL and a 38% water, non-ionic hydrogel CL was evaluated in an Australian and an
      Indian population. Fifty wearers were repeatedly sampled over 18 months.
      Overnight CL use did not alter the frequency of positive cultures, nor the
      spectrum of organisms compared with daily CL wear. There were no differences in
      type and frequency of CL contamination between the CL types. Positive cultures
      were more frequently recovered from the Indian population compared with the
      Australian population. Streptococcus spp. and Propionibacterium spp. were more
      frequently isolated from the Australian population. Fungi and Bacillus spp. were
      more frequently isolated from the Indian population. Normal CL biota alone cannot
      explain the increased rate of infection and inflammation in extended wear.

PMID- 9172410
TI  - The survival of Staphylococcus aureus during the fermentation and storage of
      yoghurt.
AB  - The effect of yoghurt culture Rx on the survival of Staphylococcus aureus CCM
      5984 added to milk in various concentrations was observed during the fermentation
      and storage of yoghurt. The end of the fermentation process (3.5 h) was only
      accompanied by a slight reduction. During the storage of yoghurt at 4 degrees C a
      1-2 log reduction was observed. No Staph. aureus was detected in yoghurt produced
      from milk contaminated by 10(3) Staph. aureus cells l-1 after 48 h of cold
      storage. When a concentration of 10(2) Staph. aureus cells was used for milk
      contamination, the pathogen was not recovered from yoghurt during the
      fermentation and storage. The fermentation and storage of yoghurt was accompanied
      by increases in lactic acid and titrimetric acidity, as well as by a decrease in
      pH value.

PMID- 9172411
TI  - Synergism in biofilm formation between Salmonella enteritidis and a nitrogen
      fixing strain of Klebsiella pneumoniae.
AB  - A laboratory reactor, which simulates biofilm formation in water pipes, was used
      to study interactions in biofilm formation between a nitrogen-fixing strain of
      Klebsiella pneumoniae and Salmonella enteritidis. The level of attachment of
      Salm. enteritidis was higher in the binar biofilm than in the single species
      biofilm. In the initial colonization phase the binary biofilm contained a much
      higher proportion of metabolically active cells than in single species biofilms
      formed by either Salm. enteritidis or Kl. pneumoniae. When a pulse of Salm.
      enteritidis was passed over an already established biofilm of Kl. pneumoniae it
      rapidly became integrated into the biofilm, from where it was subsequently
      released into the water column, along with Kl. pneumoniae. Klebsiella pneumoniae
      fixed nitrogen in the presence of Salm. enteritidis in both types of biofilm.

PMID- 9172412
TI  - Simple analysis of diphenylmethane antihistaminics and their analogues in bodily
      fluids by headspace solid-phase microextraction-capillary gas chromatography.
AB  - Thirteen antihistaminic drugs and their analogues are tested for their extraction
      by headspace solid-phase microextraction from human whole blood and urine. Their
      determination is made by using capillary gas chromatography with flame ionization
      detection. Relatively high recoveries are obtained for terodiline,
      diphenhydramine, diphenylpyraline, and orphenadrine in urine; but the recoveries
      in blood extracts are 4-51 times lower than those in urine extracts for all
      drugs. Benactyzine and piperilate are not suited for the extraction method. The
      calibration curves are drawn for four drugs spiked to whole blood and for eleven
      drugs spiked to urine; excellent linearity is confirmed for the drugs. The
      detection limits for the drugs are 76-473 ng/mL in blood and 13-186 ng/mL in
      urine. Diphenhydramine is determined for whole blood obtained from a male subject
      who had received oral administration of 30 mg diphenhydramine-HCl 150 min before
      the sampling; the concentrations of the drug are 0.12 and 1.22 micrograms/mL for
      blood and urine, respectively.

PMID- 9172413
TI  - Liquid chromatographic sample cleanup coupled on-line with gas chromatography in
      the analysis of beta-blockers in human serum and urine.
AB  - An on-line coupled reversed-phase liquid chromatographic-gas chromatographic (LC
      GC) method with minimal manual sample preparation is developed for the analysis
      of metoprolol, oxprenolol, propranolol, timolol, and codeine (as an internal
      standard) in human serum and urine. The method is based on a loop-type interface
      and concurrent eluent evaporation technique. On-line liquid-liquid extraction
      (LLE) is used to extract the analytes from aqueous eluent to organic solvent
      before injection onto the GC, and the two phases are separated with a sandwich
      type phase separator. The LC is used for cleanup, and the GC is used for the
      final separation and detection of the analytes. Total analysis time is less than
      45 min, which is much less than those of traditional analysis methods. Recoveries
      in LC cleanup and on-line LLE are excellent. A marked increase in the recoveries
      with on-line LLE is obtained by heating the aqueous eluent and the extraction
      coil. Linearity and repeatability of the method are good for both serum and
      urine, and the limits of quantitation for the analytes are 18-44 ng/mL.

PMID- 9172414
TI  - Determination of esterase-catalyzed cocaine metabolite formation by high
      performance liquid chromatography with ultraviolet detection.
AB  - A reversed-phase high-performance liquid chromatographic (HPLC) method for the
      determination of cocaine metabolites produced in vitro by serum and liver
      esterases is described. Hydrolysis of cocaine at the methyl ester bond produces
      benzoylecgonine and methanol, whereas hydrolysis at the benzoyl ester bond
      produces ecgonine methyl ester and benzoic acid. This method quantitates benzoic
      acid (as a measure of ecgonine methyl ester formation) and benzoylecgonine, which
      can be determined simultaneously and with great sensitivity by HPLC and
      ultraviolet detection. Cocaine is found to be hydrolyzed to both ecgonine methyl
      ester and benzoylecgonine; hepatic microsomes exhibit the highest specific
      activity.

PMID- 9172415
TI  - Processing of artificial visual feedback in the walking fruit fly Drosophila
      melanogaster.
AB  - A computerized 360 degrees panorama allowed us to suppress most of the locomotion
      induced visual feedback of a freely walking fly without neutralizing its
      mechanosensory system ('virtual open-loop' conditions). This novel paradigm
      achieves control over the fly's visual input by continuously evaluating its
      actual position and orientation. In experiments with natural visual feedback
      (closed-loop conditions), the optomotor turning induced by horizontal pattern
      motion in freely walking Drosophila melanogaster increased with the contrast and
      brightness of the stimulus. Conspicuously striped patterns were followed with
      variable speed but often without significant overall slippage. Using standard
      open-loop conditions in stationary walking flies and virtual open-loop or closed
      loop conditions in freely walking flies, we compared horizontal turning induced
      by either horizontal or vertical motion of appropriately oriented rhombic
      figures. We found (i) that horizontal displacements and the horizontal-motion
      illusion induced by vertical displacements of the oblique edges of the rhombic
      figures elicited equivalent open-loop turning responses; (ii) that locomotion
      induced visual feedback from the vertical edges of the rhombic figures in a
      stationary horizontal position diminished the closed-loop turning elicited by
      vertical displacements to only one-fifth of the response to horizontal
      displacements; and (iii) that virtual open-loop responses of mobile flies and
      open-loop responses of immobilized flies were equivalent in spite of delays of up
      to 0.1 s in the generation of the virtual stimulus. Horizontal compensatory
      turning upon vertical displacements of oblique edges is quantitatively consistent
      with the direction-selective summation of signals from an array of elementary
      motion detectors for the horizontal stimulus components within their narrow
      receptive fields. A compensation of the aperture-induced ambiguity can be
      excluded under these conditions. However, locomotion-induced visual feedback
      greatly diminished the horizontal-motion illusion in a freely walking fly. The
      illusion was used to assay the quality of open-loop simulation in the new
      paradigm.

PMID- 9172416
TI  - Contraction kinetics of red muscle in scup: mechanism for variation in relaxation
      rate along the length of the fish.
AB  - We studied possible mechanisms for the twofold difference in red muscle
      relaxation times between the posterior (207.2 ms) and anterior (98.4 ms)
      musculature of scup Stenotomus chrysops, which has been shown to have a large
      effect on power generation during swimming. This difference was not due to
      contamination of the anterior bundles with faster fiber types, as histological
      examination showed that all bundles contained more than 98.9% red fibers.
      Further, maximum velocities of shortening (Vmax) at 20 degrees C were nearly
      identical, 5.37 MLs-1 (where ML is muscle length) for the anterior musculature
      and 5.47 MLs-1 for the posterior musculature, suggesting that the difference in
      relaxation times was not due to a difference in the crossbridge detachment rates
      associated with different myosin isoforms. The possibility of differences in the
      Ca2+ pumping rate influencing relaxation rate was explored using cyclopiazonic
      acid (CPA), a sarcoplasmic reticulum (SR) Ca(2+)-ATPase inhibitor. The
      concentration of CPA could be adjusted to slow the relaxation rate of an anterior
      muscle to that of a posterior muscle. However, SDS gels showed no difference in
      the intensity of SR Ca(2+)-ATPase protein bands between muscle positions. These
      results suggest that differences in the Ca2+ pumping could account for the
      observed difference in relaxation rate, but do not support the simplest
      hypothesis that the difference in relaxation rates is due to differences in
      numbers of Ca2+ pumps. Other possible mechanisms for this difference are
      explored.

PMID- 9172417
TI  - Mental rotation in a California sea lion (Zalophus californianus).
AB  - Mental rotation is a widely accepted concept that suggests an analogue mode of
      visual information-processing in certain visuospatial tasks. Typically, these
      tasks demand the discrimination between the image and mirror-image of rotated
      figures, for which human subjects need an increasing reaction time depending on
      the angular disparity between the rotated figures. In pigeons, tests of this kind
      yielded a time-independent rotational invariance, suggested as being the result
      of a non-analogue information-processing that has evolved in response to the
      horizontal plane that birds perceive from above while flying. Given that marine
      mammals use the water surface as the horizontal plane for orientation while
      diving, the ability of a California sea lion to mentally rotate two-dimensional
      shapes was tested. Using a successive two-alternative matching-to-sample
      procedure, the animal had to decide between the image and mirror-image of a
      previously shown sample. Both stimuli were rotated by a multiple of 30 degrees
      with respect to the sample. The animal's reaction time was measured by a computer
      controlled touch-screen device, rewarding the animal for pressing its snout
      against the stimulus matching the sample. A linear regression analysis of the
      animal's mean reaction time against the angular rotation of the stimulus yielded
      a significant correlation coefficient. Thus, the present data can be explained by
      the mental rotation model, predicting an image-like representation of visual
      stimuli in this species. The present results therefore correspond well with those
      found for human subjects, but are inconsistent with the data reported for
      pigeons.

PMID- 9172418
TI  - Postnatal development of body architecture and gait in several rodent species.
AB  - Observations on five species of rodents, vole (Microtus socialis), gerbil
      (Gerbillus dasyurus), jird (Meriones tristrami), dormouse (Eliomys melanurus) and
      jerboa (Jaculus orientalis), revealed that, during the period when their neonates
      share a matching morphology, they also share the same forms of quadruped
      locomotion (gaits). The order in which the different gaits develop is similar in
      all species, beginning with the basic gaits of lateral walk and trot. Gaits and
      body morphology do not undergo further changes in voles, whereas the other
      species incorporate more specialized gaits later in ontogeny, when the adult body
      morphology has been attained. Gerbils and jirds incorporate a bounding gait,
      dormice incorporate galloping and jerboas incorporate bipedal running. Species
      with more specialized locomotion thus undergo more developmental stages than
      those with less specialized locomotion. Except for the jerboa, the nesting period
      was roughly the same for all species, but those with more specialized locomotion
      exhibited earlier onset of the basic gaits as if condensing their development in
      order to reach the adult gait within the same nesting period. Consequently, the
      adult gait emerges approximately 10 days before the end of nesting, regardless of
      nesting duration. Since growth rate does not seem to account for the differences
      in morphology and onset of gaits, the heterochrony in the observed species
      probably stems from differences in the duration of growth, which seems to be the
      key factor in the diversion from the basic common morphology. The present results
      reconfirm the traditional generalities of functional morphology derived from
      cross-species comparisons. In addition, they provide another perspective by
      comparing form and function within the same individuals in the course of
      ontogeny.

PMID- 9172419
TI  - Interneuronal and motor patterns during crawling behavior of semi-intact leeches.
AB  - Semi-intact tethered preparations were used to characterize neuronal activity
      patterns in midbody ganglia of the medicinal leech during crawling. Extra- and
      intracellular recordings were obtained from identified interneurons and from
      motor neurons of the longitudinal and circular muscles during crawling episodes.
      Coordinated activities of nine excitatory and inhibitory motor neurons of the
      longitudinal and circular muscles were recorded during the appropriate phases of
      crawling. Thus, during crawling, the leech uses motor output components known to
      contribute to other types of behavior, such as swimming or the shortening/local
      bending reflex. Interneurons with identified functions in these other types of
      behavior exhibit membrane potential oscillations that are in phase with the
      behavior pattern. Therefore, the recruitment of neuronal network elements during
      several types of behavior occurs not only at the motor neuron level but also
      involves interneurons. This applies even to some interneurons that were
      previously thought to have dedicated functions (such as cells 204 and 208 and the
      S cell). The function of neuronal circuitries in producing different types of
      behavior with a limited number of neurons is discussed.

PMID- 9172420
TI  - In vitro susceptibility of Tanzanian wild isolates of Plasmodium falciparum to
      artemisinin, chloroquine, sulfadoxine/pyrimethamine and mefloquine.
AB  - A 30-h in vitro susceptibility test of Plasmodium falciparum wild isolates to
      artemisinin, chloroquine, sulfadoxine/pyrimethamine and mefloquine was performed
      in Kibaha, Tanzania. A sigmoid Emax model was fitted to all data for each isolate
      and drug combination. Artemisinin and mefloquine exhibited 100% growth inhibition
      against all isolates tested (n = 69-74). The EC30 values for artemisinin and
      mefloquine were 44 and 146 nM respectively. Chloroquine and sulfadoxine/
      pyrimethamine resistance was 30% and 13% respectively. Susceptibility parameters
      (EC50,90,95 and 92 values and s) varied between compounds and isolates indicating
      the different sensitivity of P. falciparum isolates. No correlation between
      susceptibility parameters of artemisinin and the other compounds was found. The
      high in vitro activities of artemisinin and mefloquine indicate their potential
      role for the treatment of multidrug-resistant malaria in Africa.

PMID- 9172421
TI  - Mapping of the antigenic determinants of the Leishmania infantum gp63 protein
      recognized by antibodies elicited during canine visceral leishmaniasis.
AB  - The gp63 gene encoding the major surface antigen of Leishmania infantum has been
      cloned and sequenced. In spite of the overall sequence homology with the gp63
      genes from other Leishmania species, particularly with the constitutively
      expressed Leishmania chagasi Gp63 gene, the carboxy-terminal ends of these genes
      are clearly divergent (62% homology). To study the prevalence of anti-gp63
      antibodies in the sera from dogs with visceral leishmaniasis, a recombinant L.
      infantum gp63 protein was expressed in Escherichia coli. It was found that 100%
      of the sera from these dogs recognized the recombinant gp63 protein, suggesting
      that it must function as a potent B cell immunogen during natural canine visceral
      leishmaniasis. However, heterogeneity in the level of response was observed. Fine
      mapping of the antigenic determinants was performed by means of 6 overlapping
      subfragments of the gp63 protein and by the use of a library of synthetic
      peptides. The data showed that there is some degree of immunological restriction
      in the recognition of the protein since reactivity was observed preferentially
      against the most divergent region. The epitope mapping of this region showed 2
      immunodominant peptides the response to which seems to be preferentially of the
      IgG2 type.

PMID- 9172422
TI  - LSSP-PCR for characterization of strains of Entamoeba histolytica isolated in
      Brazil.
AB  - Strains of Entamoeba histolytica isolated in Brazil were characterized using the
      Low-Stringency Single Specific Primer PCR (LSSP-PCR), that detects single or
      multiple mutations in gene size DNA fragments. Using this technique, a 482-bp
      genomic DNA fragment from a structural gene in 8 strains and 2 clones of E.
      histolytica, isolated from symptomatic and asymptomatic patients in Brazil,
      including pathogenic and non-pathogenic zymodemes were studied. The results
      obtained indicate that LSSP-PCR is a valuable method for differentiating strains
      of E. histolytica. Moreover, the results are consistent with the concept that
      pathogenic and non-pathogenic strains of E. histolytica may represent distinct
      species or subspecies and are in accord with phenotypically characteristic
      isoenzyme patterns.

PMID- 9172423
TI  - Physical mapping across the dihydrofolate reductase-thymidylate synthase
      chromosome of Leishmania major.
AB  - We have used a chromosome-specific approach to generate a 300 kb long 'contig'
      across Leishmania major 500 kb chromosome. Clones from a 13-hit genomic library
      served as templates to generate end-specific probes that were used in
      hybridization to a high density array of the library. The 'contig' generated
      contained 12 markers uniformly spaced. Three restriction endonucleases were
      mapped within the map extending its resolution. Map extension indicated a
      peculiar feature of sequence organization in subtelomeric regions where
      chromosome-specificity of mapping is lost. End-probes generated from clones
      mapping to the extremes of a 300 kb 'contig' rescued a high percentage of 2 types
      of clones from the genomic library, 1 of which showed positive hybridization to
      the hexameric telomere repeat. Fine mapping at these regions revealed that these
      2 clones contained elements common to all chromosomes of the parasite. The
      physical map generated constitutes ready-to-use data for the study of many
      aspects of genome organization. Being cloned in a shuttle vector, the genomic
      sequences reordered in the map can be used to generate genetic information by
      transfection into the parasite.

PMID- 9172424
TI  - Pharmacological effects of nematode FMRFamide-related peptides (FaRPs) on muscle
      contractility of the trematode, Fasciola hepatica.
AB  - The physiological effects of synthetic replicates of the nematode FaRPs, AF1
      (KNEFIRFamide), AF2 (KHEYLRFamide), PF1 (SDPNFLRFamide), PF2 (SADPNFLRFamide),
      AF8/PF3 (KSAYMRFamide) and PF4 (KPNFIRFamide) were examined on muscle
      preparations of the liver fluke, Fasciola hepatica. Changes in contractility
      following the addition of the test compound were recorded using a photo-optic
      transducer system. Unlike the varied effects these peptides have on nematode
      somatic musculature, all were found to induce excitatory responses in the muscle
      activity of F. hepatica. While qualitative effects of the nematode peptides were
      similar in that they induced increases in both the amplitude and frequency of F.
      hepatica muscle contractions, they varied considerably in the potency of their
      excitatory effects. The threshold activity for each peptide was as follows: 10
      microM, PF1 and PF2; 3 microM, AF1 and PF3; 1 microM, AF2; and 30 nM, PF4. The
      results demonstrate, for the first time, the cross-phyla activity of nematode
      neuropeptides on the neuromuscular activity of a trematode.

PMID- 9172425
TI  - Vaccination trials against Taiwan Taenia eggs in pigs injected with frozen
      oncospheres of Taiwan Taenia, Korea Taenia, T. saginata or T. solium.
AB  - When Small-Ear-Miniature pigs subcutaneously injected once with frozen
      oncospheres of Taiwan Taenia, Korea Taenia, T. saginata or T. solium emulsified
      with Freund's complete adjuvant (1.6 x 10(4)/0.4 ml) were challenged orally with
      1.6 x 10(4) viable eggs of Taiwan Taenia 41 days later, they all showed strong
      resistance compared with pigs vaccinated with T. solium. Most pigs (5/8) of the
      former 3 groups harboured no cysticerci. The number of cysticerci was 5.5 +/- 9.1
      (mean +/- S.D.), whereas pigs of the T. solium group and control group harboured
      160 +/- 30.1 and 661 +/- 637.2 cysticerci, respectively. All cysticerci recovered
      from vaccinated pigs and most cysticerci in control pigs were degenerated or
      calcified at 36-55 days after oral egg challenge. These results strongly suggest
      that oncospheres of Taiwan Taenia and Korea Taenia are very similar to T.
      saginata in their immunogenicity in pigs.

PMID- 9172426
TI  - Identification and partial characterization of a myosin-like protein from
      cysticerci and adults of Taenia solium using a monoclonal antibody.
AB  - The host-parasite relationship in taeniosis due to Taenia solium is practically
      unknown. Monoclonal antibodies were prepared against whole extracts of adult T.
      solium parasites and evaluated with tapeworms recovered from experimentally
      infected hamsters and with cysticerci from naturally infected pigs. With one
      antibody, mAb 4B3, it was possible to identify, purify and partially characterize
      a T. solium myosin. Some findings indicate that it corresponds to conventional
      myosin or myosin type II such as: purification with KCl, high molecular weight,
      size, structure (dimeric protein with globular and long tail portions), reaction
      with commercial anti-myosin antibodies, distribution in muscle fibres of
      parasites and cross-reactivity with antibodies against paramyosin from T. solium
      cysticerci. The reaction of the mAb was only with taeniids and not with other
      parasites. Also myosin was detected in faeces of infected animals and in
      supernatants of parasite cultures. Its presence in biological fluids may be
      useful for diagnosis of infected hosts.

PMID- 9172427
TI  - The impact of diets varying in carbohydrates resistant to endogenous enzymes and
      lignin on populations of Ascaris suum and Oesophagostomum dentatum in pigs.
AB  - The impact of diets varying in type and level of carbohydrates resistant to
      endogenous enzymes and lignin on the establishment and location of Ascaris suum
      and Oesophagostomum dentatum was investigated experimentally. Fifty worm-free
      pigs, from a specific pathogen-free farm were used. The animals were assigned
      randomly to 5 diets and infected with 600 infective A. suum eggs and 6000
      infective larvae of O. dentatum per pig. The diets consisted of a traditional
      ground barley plus protein feed (diet A), commercial full-constituent pelleted
      feed (diet B), barley flour plus protein (diet C), barley flour, inulin
      (Raftiline ST, ORAFTI, Tienen, Belgium), sugar beet fibre plus protein (diet D),
      and barley flour, wheat bran, and protein (diet E). The faecal egg excretion was
      followed and the pigs were slaughtered at 8 weeks p.i. and samples taken from the
      small and large intestine. Intestinal contents were analysed for worm burdens,
      worm location and female worm fecundity along with the concentration of insoluble
      (chromic oxide) and soluble (polyethylene glycol-4000) markers, lignin, non
      starch polysaccharides (NSP) and organic acids. In all diet groups A. suum worm
      burdens were low and comparable, whereas the O. dentatum worm burdens were
      significantly higher in pigs fed the diets with high levels of NSP and lignin
      (diets A and E) than in pigs fed diets B, C, and D. The present study suggests
      that a diet rich in lignin and insoluble NSP's provides favourable conditions for
      the establishment of O. dentatum in the large intestine of pigs while it is
      unlikely that the concentration of short-chain fatty acids and pH plays and major
      role.

PMID- 9172428
TI  - Glycogen: its importance in the infectivity of aged juveniles of Steinernema
      carpocapsae.
AB  - Infective juveniles (IJs) of Steinernema carpocapsae (All) are able to remain
      relatively highly infective even when they have almost exhausted their neutral
      lipid reserves. This is not seen in other steinernematid species so we proposed
      that carbohydrate may be important for infectivity in aging IJs of S.
      carpocapsae. The present study investigated glycogen utilization in IJs of 4
      entomopathogenic nematodes, S. carpocapsae, S. riobravis (Biosys 355), S. feltiae
      (UK76) and S. glaseri (NC), stored in distilled water at 25 degrees C. The 4
      species had appreciable amounts of glycogen; from ca. 8% dry weight in S.
      riobravis to ca. 18% in S. glaseri. Infective juveniles of S. carpocapsae and S.
      riobravis survived for 120-135 days and utilized ca. 90% of their glycogen
      reserve at an almost constant rate during a 112-day storage period. Steinernema
      feltiae and S. glaseri lived for much longer (> 450 days) and during a 250-day
      storage period their glycogen content decreased by 27 and 40%, respectively. In
      contrast to the other 3 species, the rate of lipid decline preceded that of
      glycogen in S. carpocapsae. The rate of glycogen decline in S. carpocapsae IJs
      incubated with the glycolytic inhibitor, iodoacetamide (10(-4) M) was
      significantly reduced (P < 0.05) compared with untreated nematodes, and the
      infectivity of inhibitor-treated aged (> 80 days) IJs was reduced compared with
      controls. Incubating aged (80-day) IJs of S. carpocapsae (mean neutral lipid
      content ca. 10% of initial level) with 10(-4) M iodoacetamide for 24 h
      significantly reduced (P < 0.05) their infectivity compared with freshly
      harvested inhibitor-treated IJs and untreated controls. Following an 11-day
      recovery period, the infectivity of inhibitor-treated aged IJs recovered
      significantly (P < 0.05). The evidence suggests that glycogen is an important
      source of energy for maintaining infectivity in aged IJs of S. carpocapsae.

PMID- 9172429
TI  - Effects of infected insects on secondary invasion of steinernematid
      entomopathogenic nematodes.
AB  - Factors affecting 'invasion efficiency' of steinernematid entomopathogenic
      nematodes into hosts were elucidated. The phenomenon that only part (10-40%) of
      the nematode population invades the target host has been recorded in many
      studies. It has been mainly ascribed to differences in the ability of individual
      nematodes to infect. In the present study the effect of an infected host, the wax
      moth Galleria mellonella, on subsequent infection of the entomopathogenic
      nematodes Steinernema carpocapsae Mexican, S. riobravus and S. feltiae was
      evaluated. The invasion rate of the 3 nematode species to a non-infected host was
      reduced by 40-60% after pre-exposure to infected hosts. These nematodes regained
      their full invasion potential after they were rinsed with water. Invasion into
      insects which were previously injected with nematodes was significantly reduced
      by 60-80% 6-9 h after injection. The reduction in subsequent invasion due to the
      initial infection was nematode species specific. This phenomenon was also
      observed with other lepidopteran pests (Helicoverpa armigera and Spodoptera
      littoralis). The data indicate that the initial infection by entomopathogenic
      nematodes induced the release of a substance which reduced the subsequent
      invasion. The chemical and biological characteristics of this substance are
      currently under investigation.

PMID- 9172430
TI  - Characterization of two cDNAs encoding cysteine proteinases from the soybean cyst
      nematode Heterodera glycines.
AB  - Two cDNAs encoding cysteine proteinases were isolated from a cDNA library
      constructed from feeding females of Heterodera glycines. The library was screened
      with a cysteine proteinase gene fragment originally amplified from cDNA of H.
      glycines. Database searches predict that 1 cDNA (hgcp-I) encodes a cathepsin L
      like proteinase, while the second (hgcp-II) encodes a cathepsin S-like enzyme.
      Both predicted proteins contain a short secretion signal sequence, a long
      propeptide and a mature protein of 219 amino acids. Southern blot analysis
      suggests that the cathepsin S-like enzyme, HGCP-II, is encoded by a single-copy
      gene in contrast to the cathepsin L-like proteinase, HGCP-I which may have 2
      homologues. The regions encoding the mature proteinases were cloned into an
      expression vector and recombinant protein produced in E. coli. HGCP-I was shown,
      after refolding, to cleave the synthetic peptide Z-Phe-Arg-AMC, and this activity
      could be inhibited by the engineered rice cystatin Oc-I delta D86. HGCP-II showed
      no activity against the synthetic substrates tested. The knowledge gained from
      these studies will improve our understanding of plant nematode proteinases and
      aid the development of a rational proteinase inhibitor-based approach to plant
      nematode resistance.

PMID- 9172431
TI  - Partial purification, characterization and nitrogen regulation of the lysine
      epsilon-aminotransferase of Streptomyces clavuligerus.
AB  - The L-lysine epsilon-aminotransferase (LAT) of Streptomyces clavuligerus was
      partially purified and characterized. The 51.3-kDa enzyme exhibited optimal
      activity at pH 7.0-7.5 and 30 degrees C. It catalyzed transfer of the terminal
      amino group of L-lysine or L-ornithine to alpha-ketoglutarate. Oxalacetate and
      pyruvate were also used as acceptors of the amino group but with very low
      efficiency. Increasing ammonium concentrations added to chemically-defined medium
      MM enhanced the formation of LAT and decreased production of cephalosporins by S.
      clavuligerus. In cultures grown in the absence of lysine, greater enhancement of
      LAT formation by ammonium and less repression of cephalosporin biosynthesis were
      observed. In the chemically-defined GSPG medium, ammonium ions decreased
      cephalosporin production without showing an effect on LAT formation.

PMID- 9172432
TI  - Process optimization for large-scale production of TGF-alpha-PE40 in recombinant
      Escherichia coli: effect of medium composition and induction timing on protein
      expression.
AB  - The effects of medium composition and induction timing on expression of a
      chimeric fusion protein TGF-alpha-PE40 (TP-40) in Escherichia coli strain RR1
      were examined using a complex medium at several fermentor scales. Two distinctive
      phases in E. coli catabolism were identified during fermentation based on
      preferential utilization between protein hydrolysate and glycerol. Maximum
      specific and volumetric productivities were achieved by inducing the culture when
      the cells were switching substrate utilization from protein hydrolysate to
      glycerol. By increasing the yeast extract concentration in the production medium,
      initiation of the catabolic switch was delayed until high cell mass was achieved.
      The final titer of TP-40 at the 15-L fermentation scale was doubled from 400 mg L
      1 to 850 mg L-1 by increasing the yeast extract concentration from 1% to 4% (w/v)
      and delaying the time of induction. This fermentation process was rapidly scaled
      up in 180-L and 800-L fermentors, achieving TP-40 titers of 740 and 950 mg L-1,
      respectively.

PMID- 9172433
TI  - Diversity of isolates of Acinetobacter from activated sludge systems based on
      their whole cell protein patterns.
AB  - Whole cell protein extracts from strains of the currently recognized genomic
      species of Acinetobacter, together with those from a range of isolates of several
      genomic species identified using the Biolog system and obtained from a biological
      nutrient-removal activated sludge plant were analysed by SDS-PAGE. The
      dendrograms obtained after numerical analysis for the known genomic species
      generally supported the taxonomic relationships suggested from earlier DNA-DNA
      hybridisation data. In some cases the activated sludge isolates identified to
      genomic species level clustered closely with the corresponding genomic species
      reference strains, although isolates 5 and 8/9 were scattered throughout the
      dendrogram. Considerable variations were seen in the protein patterns of the 27
      different environmental isolates of genomic species 7 that were analysed. Three
      unidentified Acinetobacter isolates examined formed their own subcluster.

PMID- 9172434
TI  - Caroteno-protein and exopolysaccharide production by co-cultures of Rhodotorula
      glutinis and Lactobacillus helveticus.
AB  - The lactose-negative yeast Rhodotorula glutinis 22P and the homofermentative
      lactic acid bacterium Lactobacillus helveticus 12A were cultured together in a
      cheese whey ultrafiltrate containing 42 g L-1 lactose. The chemical composition
      of the caroteno-protein has been determined. The carotenoid and protein contents
      are 248 micrograms g-1 dry cells and 48.2% dry weight. Carotenoids produced by
      Rhodotorula glutinis 22P have been identified as beta-carotene 15%, torulene 10%,
      and torularhodin 69%. After separating the cell mass from the microbial
      association, the exopolysaccharides synthesized by Rhodotorula glutinis 22P were
      isolated from the supernatant medium in a yield of 9.2 g L-1. The monosaccharide
      composition of the synthesized biopolymer was predominantly D-mannose (57.5%).

PMID- 9172435
TI  - Use of virginiamycin to control the growth of lactic acid bacteria during alcohol
      fermentation.
AB  - The antibiotic virginiamycin was investigated for its effects on growth and
      lactic acid production by seven strains of lactobacilli during the alcoholic
      fermentation of wheat mash by yeast. The lowest concentration of virginiamycin
      tested (0.5 mg Lactrol kg-1 mash), was effective against most of the lactic acid
      bacteria under study, but Lactobacillus plantarum was not significantly inhibited
      at this concentration. The use of virginiamycin prevented or reduced potential
      yield losses of up to 11% of the produced ethanol due to the growth and
      metabolism of lactobacilli. However, when the same concentration of virginiamycin
      was added to mash not inoculated with yeast, Lactobacillus rhamnosus and L.
      paracasei grew after an extensive lag of 48 h and L. plantarum grew after a
      similar lag even in the presence of 2 mg virginiamycin kg-1 mash. Results showed
      a variation in sensitivity to virginiamycin between the different strains tested
      and also a possible reduction in effectiveness of virginiamycin over prolonged
      incubation in wheat mash, especially in the absence of yeast.

PMID- 9172436
TI  - Regulatory components, including integration host factor, CysB and H-NS, that
      influence pH responses in Escherichia coli.
AB  - This review describes a range of pH responses. Some are only induced if relevant
      DNA is brought to an appropriately supercoiled configuration by DNA gyrase and
      bent by the action of, for example, integration host factor (IHF). Bending may
      allow transcription by bringing activators into juxtaposition with RNA
      polymerase, which is CysB-associated in several of the responses. Control of
      arginine decarboxylase (AdiA) synthesis at acid pH is of the above type, with
      dependence on the presence of gyrase, H-NS, IHF and CysB; acid induction of LysU
      has similar requirements but also needs Lrp; lysine decarboxylase (CadA)
      formation at acid pH is controlled quite differently, needing the CadC activator
      and interaction of lysine/lysine permease; H-NS probably reverses induction by
      CadC. The Hyd components of formic hydrogenlyase are induced by acid under
      anaerobiosis; a transcriptional activator is involved and Fur may also function
      in regulation. Acid tolerance induced at low pH in log-phase cells needs CysB and
      PhoE but not DNA gyrase; tolerance is reduced by NaCl but not affected by Fe3+,
      Fe2+, glucose/cAMP or by lrp, him, fur, hns or nhaA/B lesions. Alkali tolerance
      (habituation), induced at pH0 8.5-9.0, probably involves DNA supercoiling and
      bending; the induction process needs IHF, CysB, PhoE, NhaA, TonB and Fur and is
      glucose-repressed; tolerance may result from Na+ efflux catalysed by the NhaA
      antiporter, which is induced at pH0 9.0. Alkali sensitivity induced at pH0 5.5
      also requires gyrase, IHF and CysB, but H-NS, Lrp, NhaA and OmpC are also needed
      and induction is abolished by NaCl. Salt-induced acid sensitivity results from
      PhoE formation and is blocked by glucose (reversed by cAMP), FeCl3 and hns and
      relA lesions, the effect of relA being envZ-suppressed. Acid sensitivity
      induction (ASI) at pH0 9.0 needs H-NS, is inhibited by FeCl3 and amiloride, and
      is associated with alkyl hydroperoxide reductase synthesis. Leucine-induced acid
      sensitivity needs gyrase, CysB, H-NS, Fur, OmpA and RelA, is inhibited by Fe3+,
      Fe2+, tetracycline, glucose and nalidixic acid, but not by chloramphenicol;
      increased outer membrane proton passage may result from OmpA modification.

PMID- 9172437
TI  - Total biodegradation of the oestrogenic mycotoxin zearalenone by a bacterial
      culture.
AB  - A mixed culture of bacteria, enriched from soil collected at a coal gasification
      site, proved capable of removing the potent oestrogenic mycotoxin zearalenone
      from culture media. The bacteria grew rapidly when zearalenone was provided as
      the sole source of carbon and energy. HPLC and ELISA analysis of culture extracts
      revealed no zearalenone or zearalenone-like products. Fourteen bacterial isolates
      from the mixed culture were identified and purified. The ability to degrade
      zearalenone was lost upon purification and recombination of the bacterial members
      of the mixed culture. A strain of Pseudomonas fluorescens capable of degrading
      polychlorinated biphenyls was unable to degrade zearalenone. This is the first
      report of the complete degradation of zearalenone by bacteria. The present study
      suggests the potential of mixed cultures in the biodegradation of zearalenone.

PMID- 9172438
TI  - A closed system for the filtration of Mycobacterium bovis liquid cultures using
      disposable capsule filters.
AB  - A filtration system was designed to sterilize large volumes of Mycobacterium
      bovis BCG Tokyo culture safely, needed to purify protein antigens for
      immunodiagnosis of bovine tuberculosis. A closed system consists of culture
      bottles connected to three disposable filter capsules of decreasing pore size in
      series: a depth prefilter over a 1.2 microns filter; 0.8 micron prefilter over a
      0.45 micron filter; and a 0.2 micron sterile filter. Low air pressure (3 psi)
      forces liquid from below the bacillary pellicle. The system features a stainless
      steel clamp to hold rubber stoppers on the culture bottles, pleated filters to
      exclude bacillary clumps, a quick disconnector to minimize aerosols, and a closed
      system with plastic disposable filters that can be autoclaved as a unit without
      dismantling.

PMID- 9172439
TI  - The use of the bacteriocin, nisin, as a preservative in ricotta-type cheeses to
      control the food-borne pathogen Listeria monocytogenes.
AB  - The efficacy of nisin to control the food-borne pathogen Listeria monocytogenes
      in ricotta-type cheeses over long storage (70 d) at 6-8 degrees C was determined.
      Cheeses were prepared from unpasteurized milk by direct acidification with acetic
      acid (final pH 5.9) and/or calcium chloride addition during heat treatment. Nisin
      was added in the commercial form of Nisaplin pre-production to the milk. Each
      batch of cheese was inoculated with 10(2)-10(3) cfu g-1 of a five-strain cocktail
      of L. monocytogenes before storage. Shelf-life analysis demonstrated that
      incorporation of nisin at a level of 2.5 mg l-1 could effectively inhibit the
      growth of L. monocytogenes for a period of 8 weeks or more (dependent on cheese
      type). Cheese made without the addition of nisin contained unsafe levels of the
      organism within 1-2 weeks of incubation. Measurement of initial and residual
      nisin indicated a high level of retention over the 10-week incubation period at 6
      8 degrees C, with only 10-32% nisin loss.

PMID- 9172440
TI  - Survival of Escherichia coli O157:H7 in yoghurt during preparation and storage at
      4 degrees C.
AB  - Cow's milk was inoculated with ca 10(3) and 10(7) cfu ml-1 Escherichia coli
      O157:H7. After fermentation at 42 degrees C for 0-5 h, the yoghurt was stored at
      4 degrees C. Two kinds of yoghurt were used: traditional yoghurt (TY), made with
      Streptococcus thermophilus and Lactobacillus bulgaricus starter cultures, and
      'bifido' yoghurt (BY), made with the two starter cultures plus Bifidobacterium
      bifidum. After 7 d E. coli O157:H7 decreased from 3.52 to 2.72 log10 cfu ml-1 and
      from 7.08 to 5.32 log10 cfu ml-1 in TY, and from 3.49 to 2.73 log10 cfu ml-1 and
      from 7.38 to 5.41 log10 cfu ml-1 in BY. The pH values of yoghurt dropped from 6.6
      to 4.5 and 4.4 in TY (for low and high pathogen inocula, respectively), and from
      6.6 to 4.6 and 4.5 in BY (for low and high pathogen inocula, respectively).

PMID- 9172441
TI  - The detection of Escherichia coli DNA in the ancient remains of Lindow Man using
      the polymerase chain reaction.
AB  - The polymerase chain reaction has been applied to the detection of Escherichia
      coli DNA in the upper gut contents of Lindow Man, an Iron Age bog body dated to
      ca 300 BC. With sets of primers from the uidA and lacZ genes, E. coli DNA could
      be detected reproducibly. Initial attempts at detecting DNA from freshly voided
      faeces from a healthy volunteer were unsuccessful due to inhibition of the
      reaction. Development of a method, based on guanidine thiocyanate and silica
      extraction and purification of the DNA fragments, facilitated the detection of
      the E. coli DNA in both freshly voided faeces and the upper gut contents of
      Lindow Man. These findings indicate that it may be possible to study the
      existence of infectious diseases in ancient civilizations and to learn more about
      the evolution of microbes.

PMID- 9172442
TI  - The construction and application of a lux-based nitrate biosensor.
AB  - A plasmid-borne transcriptional fusion between the Escherichia coli nitrate
      reductase (narG) promoter and the Photorhabdus luminescens lux operon provides E.
      coli with a highly bioluminescent phenotype in the presence of nitrate. This E.
      coli biosensor can detect nitrate to a level of 5 x 10(-5) mol l-1 (0.3 ppm),
      levels relevant to those levels encountered in brewing water. Since induction of
      the narG promoter requires NarL, the plasmid-based sensor can also be used to
      interrogate enteric bacteria for the presence of functional homologues of this E.
      coli regulatory protein. Obesumbacterium proteus, an important bacterial brewery
      contaminant, failed to provide nitrate-dependent bioluminescence demonstrating
      divergence in this organism from E. coli in the mechanism of nitrate reductase
      regulation.

PMID- 9172443
TI  - Recovery of Lactobacillus rhamnosus GG from human colonic biopsies.
AB  - The colonization of Lactobacillus rhamnosus GG (ATCC 53103, henceforth L.GG) in
      five human colonoscopy patients was studied. The test subjects consumed whey
      drink fermented with the bacterium for 12 d before the colonoscopy. The presence
      of L.GG was subsequently checked both in the faecal samples and in the colonic
      biopsies obtained from various locations in the large intestine. In all patients
      L.GG was the dominant faecal lactic acid bacterium as a result of the
      administration. In four patients L.GG could also be recovered from the biopsies,
      while with one patient (suffering from ulcerative colitis diagnosed during the
      colonoscopy) no L.GG was detected in the biopsy samples. The results suggest that
      L.GG is able to adhere in vivo to the colon. Study of the faecal samples alone is
      apparently not sufficient for elucidation of the gastrointestinal ecology of
      probiotic bacteria.

PMID- 9172446
TI  - A small heat shock protein from Leuconostoc oenos induced by multiple stresses
      and during stationary growth phase.
AB  - In Leuconostoc oenos, a malolactic bacterium, the synthesis of a stress protein
      called LO18 with an apparent molecular mass of 18 kDa was greatly induced after
      heat (42 degrees C), acid (pH 3) or ethanolic (12% (v/v)) shocks. Moreover, the
      LO18 protein synthesis was induced in stationary growth phase and was detected
      for a long time (30 h) during this growth phase. Significant identity was found
      between the N-terminal parts of the LO18 protein and the Hsp18 from Clostridium
      acetobutylicum suggesting that LO18 protein belongs to the family of small heat
      shock proteins conserved in prokaryotic and eukaryotic cells.

PMID- 9172444
TI  - Lactose-induced expression of Bacillus sp. TS-23 amylase gene in Escherichia coli
      regulated by a T7 promoter.
AB  - Bacillus sp. TS-23 amylase gene was amplified by polymerase chain reaction and
      cloned into the pET23(+) transcription vector. Lactose induction of Escherichia
      coli BL21(DE3) cells harbouring this recombinant plasmid resulted in the
      extracellular production of gene products. By the addition of 20 mmol l-1
      lactose, the amylase activity of fermentation broth had a specific activity of 21
      U mg-1 of protein.

PMID- 9172447
TI  - A 5-h screening and 24-h confirmation procedure for detecting Escherichia coli
      O157:H7 in beef using direct epifluorescent microscopy and immunomagnetic
      separation.
AB  - An antibody-direct epifluorescent filter technique (Ab-DEFT) detected 100% of the
      raw ground beef samples inoculated with Escherichia coli O157:H7 cells (0.15
      cells g-1) and incubated in a prewarmed, modified buffered peptone water (mBPW)
      non-selective enrichment broth for 5 h at 42 degrees C in an orbital shaking
      water bath (200 rev min-1). Over 50% of the microscopic fields viewed were
      positive (1-10 fluorescent cells field-1) in the Ab-DEFT. All positive screening
      results were confirmed within 24 h by subjecting 1 ml of the mBPW to the
      Dynabeads anti-E. coli O157 immunomagnetic separation procedure, followed by
      plating on MacConkey sorbitol agar containing 5-bromo-4-chloro-3-indolyl-beta-D
      glucuronide. At this cell concentration, 41.7% of the inoculated samples were
      detected by the conventional method involving a 24-h selective enrichment.
      Exposure to viable cells before filtration was minimized by using a 0.58%
      formaldehyde concentration for 5 min at 50 degrees C (killed > 4.00 logs of E.
      coli O157:H7 cells) without affecting cell fluorescence.

PMID- 9172448
TI  - Optimization of haemolysis in enhanced haemolysis agar (EHA)--a selective medium
      for the isolation of Listeria monocytogenes.
AB  - The presence of Listeria monocytogenes in enrichment media can be masked by
      faster growth of other Listeria spp. Therefore, enhanced haemolysis agar (EHA) is
      a good alternative for another isolation media, because the presence of a few L.
      monocytogenes colonies can be detected in a majority of colonies of other
      listeriae on the basis of haemolysis. In this study the haemolysis reaction in
      EHA was optimized. In a collaborative study using reference samples, no
      significant differences in counts on EHA, Palcam and Oxford agar were shown.

PMID- 9172449
TI  - [Mistreatment, abuse and neglect of senior citizens as a medical problem].
AB  - The author presents an account of contemporary approaches to the problem of
      maltreatment, abuse and neglect of senior citizens. He draws attention to risk
      factors, clinical manifestations and different forms of maltreatment. Briefly
      basic remedies are discussed. Special attention is devoted to maltreatment and
      unsuitable treatment in facilities for long-term care.

PMID- 9172450
TI  - [Chronobiology of human aggression].
AB  - BACKGROUND: Violence is an urgent problem concerning society as a whole. If
      chronobiological changes of human aggressiveness existed, it would be possible to
      foresee them and when an increased incidence is expected it would be perhaps
      possible to use preventive measures. METHODS AND RESULTS: The author processed
      data on 2447 aggressive acts of violence and 1028 completed suicides (aggression
      against oneself) on the territory of the former South Moravian region according
      to a weekly, annual and lunar rhythm and in relation to sudden climatic changes.
      The most remarkable finding is that the impulsive bodily harm (usually without
      economic or sexual motivation) is very closely associated with sudden climatic
      changes, while burglary and rape do not depend on climatic changes and their
      frequency correlates with the semilunar rhythm (there are two peaks during
      lunation), similarly as the frequency of sudden cardiovascular deaths. In
      suicides the frequency changes, with certain exceptions, similarly as the
      incidence of impulsive intentional bodily assault. In general close to the phase
      of full moon aggressiveness is significantly reduced and not increased, as was
      and still is believed by mistake, based on few observations and impressions.
      CONCLUSIONS: The assessed periodicities differentiate types of aggressive
      behaviour, prove the possibility of prediction of an increase of the mean
      incidence and provide thus a basis for estimation of the time and type of
      increased aggressiveness. It is thus possible to introduce preventive measures.

PMID- 9172451
TI  - [Epidemiologic autopsy of Binswanger's disease].
AB  - BACKGROUND: Binswanger's disease is the most substantial part of the continuum of
      ischemic vascular dementia (IVD). IVD is the second most frequent cause of
      dementia in industrialised countries. The frequency of IVD generally, and of the
      Binswanger's disease especially, is due to the method of statistical data
      collection, in the Czech republic not known. METHODS AND RESULTS: The crude rate
      of Binswanger's disease diagnosed histologically among the autopsies of 132 men
      and 212 woman aged 60-99 yr. performed at Thomayer's University Hospital from 1.
      7. 1995 to 1. 7. 1996 by use of by principle of "epidemiologic" autopsy was
      estimated at 7.9%. This is about a half of the crude rate of Alzheimer's disease
      found in the same cohort. By estimating of histological "ischemic score", which
      is independent on clinical data, it is possible to diagnose the Binswanger's
      disease with high probability. CONCLUSIONS: The sensitivity and specificity of
      clinical diagnosis IVD generally and of BN in particular is low. IVD/BN is one of
      the most frequent and consequential ailment in higher age groups. IVD/BN is
      preventable and curable at earlier stages of development. Knowledge and precise
      and timely diagnosis of IVD/BN is fundamentally important for patients.

PMID- 9172452
TI  - CSK associates with the TCR zeta and epsilon chains via its SH2 domain; a
      mechanism for turning off TCR signaling.
AB  - Recent biochemical and genetic studies implicate Csk (carboxy-terminal Src
      kinase) as the one of the main downregulators of the activity of members of the
      Src family of kinases. Csk is probably involved in the downregulation of TCR
      signaling by C-terminal tyrosine phosphorylation of Lck and Fyn, but the
      mechanism whereby Csk targets these Src family members is not known. Here we
      report the association of Csk with the TCR complex, an interaction mediated by
      the binding of the Csk-SH2 domain to phosphorylated zeta and epsilon chains of
      the TCR complex. The interaction with TCR brings Csk into close contact with Lck
      and Fyn which are known to be associated with TCR, either functionally and/or
      physically. This finding suggests a novel mechanism whereby TCR signaling is
      turned off.

PMID- 9172453
TI  - [Measurements of lung volume and its subdivisions by spirography].

PMID- 9172454
TI  - [Plethysmographic measurement of thoracic gas volume].

PMID- 9172455
TI  - [Measurements of residual volume and total lung capacity].

PMID- 9172456
TI  - [Flow-volume curve].

PMID- 9172457
TI  - [Differential pulmonary function].

PMID- 9172458
TI  - [Closing volume measurement and its clinical significance].

PMID- 9172459
TI  - [The measurement of pulmonary diffusing capacity for carbon monoxide].

PMID- 9172460
TI  - [Self-assessment of peak expiratory flow].

PMID- 9172461
TI  - [Assessment of pulse oximetry readings].

PMID- 9172462
TI  - [Pulmonary perfusion scintigraphy and ventilation perfusion scintigraphy].

PMID- 9172463
TI  - [Regional evaluation of ventilation by RI].

PMID- 9172464
TI  - [Evaluation of pulmonary function by expiratory CT using helical CT].

PMID- 9172465
TI  - [Pulmonary MR angiography].

PMID- 9172466
TI  - [Pulmonary magnetic field].

PMID- 9172467
TI  - [Function testing of bronchial responsiveness].

PMID- 9172468
TI  - [Bronchial inhalation challenge with antigens].

PMID- 9172469
TI  - [Respiratory muscle functional test].

PMID- 9172470
TI  - [Ventilatory response to hypoxia and hypercapnia].

PMID- 9172471
TI  - [Lung compliance].

PMID- 9172472
TI  - [Expired gas analysis].

PMID- 9172473
TI  - [Analytical method of lung sounds].

PMID- 9172474
TI  - [Tracheo bronchial mucociliary clearance].

PMID- 9172475
TI  - [Evaluation method of salivary gland function].

PMID- 9172476
TI  - [Investigation of gastric juice (gastrin stimulating test, Histalog stimulating
      test)].

PMID- 9172477
TI  - [Continuous intragastric pH monitoring].

PMID- 9172478
TI  - [Esophageal pH monitoring].

PMID- 9172479
TI  - [Measurement of gastric mucosal blood flow].

PMID- 9172480
TI  - [Lactose tolerance test].

PMID- 9172481
TI  - [Absorption test of protein].

PMID- 9172482
TI  - [Absorption test of fat].

PMID- 9172483
TI  - [Absorption test of vitamin].

PMID- 9172484
TI  - [d-xylose absorption test].

PMID- 9172485
TI  - [Gordon test].

PMID- 9172486
TI  - [Alpha 1-antitrypsin clearance].

PMID- 9172487
TI  - [Esophageal manometry].

PMID- 9172488
TI  - [Tests of gastric motility].

PMID- 9172490
TI  - [Gastric emptying test (acetaminophen method)].

PMID- 9172489
TI  - [Gastric emptying by the barium marker method].

PMID- 9172491
TI  - [Measurement of gastric emptying using radioisotope].

PMID- 9172492
TI  - [Gastric emptying study by electrical impedance tomography].

PMID- 9172493
TI  - [Gastric emptying test using helical CT].

PMID- 9172494
TI  - [Measurement of gastric emptying by MRI].

PMID- 9172495
TI  - [Electrogastrography (EGG)].

PMID- 9172496
TI  - [Clinical application of optical flow method in esophageal wall movement].

PMID- 9172497
TI  - [Color Doppler sonography of the liver].

PMID- 9172498
TI  - [Evaluation of hepatic hemodynamics on CT].

PMID- 9172499
TI  - [Estimation of portal flow by MR angiography].

PMID- 9172500
TI  - [Indocyanine green and sulfobromophthalein tests].

PMID- 9172501
TI  - [Drip infusion cholangiography combined helical computed tomography].

PMID- 9172502
TI  - [Biliary drainage test].

PMID- 9172503
TI  - [Evaluation of the biliary system and pancreatic duct using MR
      cholangiopancreatography].

PMID- 9172504
TI  - [Evaluation of gallbladder wall blood flow using color Doppler ultrasonography].

PMID- 9172505
TI  - [Secretin test (S-test)].

PMID- 9172506
TI  - [PFD test (bentiromide test, BT-PABA test)].

PMID- 9172507
TI  - [Quantitative measurement of the blood flow in the pancreas].

PMID- 9172508
TI  - [Evaluation of pancreatic function with intraductal ultrasonography (IDUS)].

PMID- 9172509
TI  - [GRH test].

PMID- 9172510
TI  - [Insulin induced hypoglycemic test].

PMID- 9172511
TI  - [Arginine test].

PMID- 9172512
TI  - [Glucagon-propranolol provocative test].

PMID- 9172513
TI  - [L-dopa provocative test].

PMID- 9172514
TI  - [Bromocriptine provocative test].

PMID- 9172515
TI  - [Oral glucose loading test].

PMID- 9172516
TI  - [TRH provocative test].

PMID- 9172517
TI  - [TRH test].

PMID- 9172518
TI  - [Metoclopramide, sulpiride, and chlorpromazine loading test].

PMID- 9172519
TI  - [L-dopa and dopamine loading test].

PMID- 9172520
TI  - [Bromocriptine loading test].

PMID- 9172521
TI  - [LH-RH (loading) test].

PMID- 9172522
TI  - [Clomiphene challenge test].

PMID- 9172523
TI  - [Estrogen challenge test].

PMID- 9172524
TI  - [Metopiron test].

PMID- 9172525
TI  - [Lysine-vasopressin test].

PMID- 9172526
TI  - [Insulin-induced hypoglycemia test].

PMID- 9172527
TI  - [Dexamethasone suppression test].

PMID- 9172528
TI  - [TRH loading test].

PMID- 9172529
TI  - [T3 (triiodo-thyronin) suppression test].

PMID- 9172530
TI  - [Carter-Robbins test].

PMID- 9172531
TI  - [Water deprivation and water load test].

PMID- 9172532
TI  - [Clinical studies in antidiuretic hormone secretion].

PMID- 9172533
TI  - [Pitressin test and DDAVP test].

PMID- 9172534
TI  - [PTH infusion test].

PMID- 9172535
TI  - [Fractional tubular reabsorption of phosphate].

PMID- 9172536
TI  - [TRH test].

PMID- 9172537
TI  - [In vivo test of thyroid radioactive iodide uptake, pertechnetate 99m uptake and
      thyroid scintigraphy].

PMID- 9172538
TI  - [Angiotensin II analogue infusion test].

PMID- 9172539
TI  - [Furosemide: upright test].

PMID- 9172540
TI  - [Captopril test].

PMID- 9172541
TI  - [Clinical studies with angiotensin II and angiotensin III].

PMID- 9172542
TI  - [Saline infusion test].

PMID- 9172543
TI  - [CRH-test].

PMID- 9172544
TI  - [ACTH test].

PMID- 9172545
TI  - [Metyrapone test].

PMID- 9172546
TI  - [Dexamethasone suppression test].

PMID- 9172547
TI  - [Glucagon test].

PMID- 9172548
TI  - [Metoclopramide test].

PMID- 9172549
TI  - [Regitine test].

PMID- 9172550
TI  - [Clonidine suppression test].

PMID- 9172551
TI  - [Evaluation of adrenal medullary function with scintigraphy].

PMID- 9172552
TI  - [Evaluation of adrenal medullary function with CT scanning].

PMID- 9172553
TI  - [Function tests for male gonads].

PMID- 9172554
TI  - [Evaluation of spermatogenic function].

PMID- 9172555
TI  - [Radioisotope penography].

PMID- 9172556
TI  - [Nocturnal penile tumescence].

PMID- 9172557
TI  - [LH-RH test, clomiphene test, Premarin test, and Kaufmann test].

PMID- 9172558
TI  - [Fetal monitoring].

PMID- 9172559
TI  - [Placental function test].

PMID- 9172560
TI  - [Insulin secretion--assay method and its significance].

PMID- 9172561
TI  - [Tolbutamide, glucagon, leucine and arginine tolerance test].

PMID- 9172562
TI  - [Somatostatin stimulation test].

PMID- 9172563
TI  - [Receptor diseases and their evaluation methods].

PMID- 9172564
TI  - [Analysis and characterization of ligand-receptor binding systems].

PMID- 9172565
TI  - [Detection of functional abnormalities of hormone receptors by gene diagnosis].

PMID- 9172566
TI  - [Receptor function and monoclonal antibody].

PMID- 9172567
TI  - [Pathophysiology of Gn-RH receptor].

PMID- 9172568
TI  - [GRH receptor].

PMID- 9172569
TI  - [CRH receptor: evaluation of the receptor functions].

PMID- 9172570
TI  - [ACTH receptor].

PMID- 9172571
TI  - [TSH receptor].

PMID- 9172572
TI  - [GH receptor function and its evaluation].

PMID- 9172573
TI  - [The functional analysis of LH receptor].

PMID- 9172574
TI  - [Structure, function and abnormality of ADH receptors].

PMID- 9172575
TI  - [PTH/PTHrP receptor].

PMID- 9172576
TI  - [Insulin receptor].

PMID- 9172577
TI  - [Somatostatin receptors].

PMID- 9172578
TI  - [Erythropoietin receptor].

PMID- 9172579
TI  - [Vitamin D receptor].

PMID- 9172580
TI  - [Interleukin-1 receptor].

PMID- 9172581
TI  - [Interleukin-2 receptor].

PMID- 9172582
TI  - [Interleukin-3 receptor].

PMID- 9172583
TI  - [Interleukin 4 receptor (IL-4R)].

PMID- 9172584
TI  - [Interleukin-5 receptor].

PMID- 9172585
TI  - [Interleukin-6 (IL-6) receptor].

PMID- 9172586
TI  - [Granulocyte-macrophage colony-stimulating factor receptor].

PMID- 9172587
TI  - [Angiotensin receptor].

PMID- 9172588
TI  - [Pathophysiological significance of natriuretic peptide receptor].

PMID- 9172589
TI  - [Androgen receptor].

PMID- 9172590
TI  - [Examination of estrogen receptor and its significance].

PMID- 9172591
TI  - [Glucocorticoid receptor].

PMID- 9172592
TI  - [Mineralocorticoid receptor].

PMID- 9172593
TI  - [Thyroid hormone receptors].

PMID- 9172594
TI  - [Scavenger receptor].

PMID- 9172595
TI  - [LDL receptor].

PMID- 9172596
TI  - [Endothelin receptor].

PMID- 9172597
TI  - [Prostanoid receptors].

PMID- 9172598
TI  - [Sulfonylurea receptor].

PMID- 9172599
TI  - [The measurement of renal plasma flow].

PMID- 9172600
TI  - [Clinical assessment of glomerular filtration].

PMID- 9172601
TI  - [Phenolsulfonphthalein test].

PMID- 9172602
TI  - [Indigocarmine test].

PMID- 9172603
TI  - [Selectivity index].

PMID- 9172604
TI  - [Concentration test and dilution test].

PMID- 9172605
TI  - [Osmolar clearance].

PMID- 9172606
TI  - [beta 2-microglobulin clearance].

PMID- 9172607
TI  - [Quantitative divided renal function studies with radionuclides-
      renoscintigraphy].

PMID- 9172608
TI  - [Renal acidification test].

PMID- 9172609
TI  - [Dynamic MR urography with SIP fast GRE method].

PMID- 9172610
TI  - [Evaluation of renal function by SPECT].

PMID- 9172611
TI  - [Proliferating cell nuclear antigen (PCNA)].

PMID- 9172612
TI  - [Clinico-pathologic spectrum of cutaneous angiosarcoma and the difficulties of
      pathologic diagnosis].

PMID- 9172613
TI  - [Histopathologic features of cytomegalovirus lymphadenitis in the
      "immunocompetent" patient. Report of 7 cases].
AB  - The authors report seven cases of cytomegalovirus lymphadenitis in apparently
      immunocompetent patients. One patient presented with an infectious mononucleosis
      like illness. The main presentation of the others was isolated cervical
      lymphadenopathies. The lymph node pathology showed aspecific lymphoid
      hyperplasia, resembling the human immunodeficiency virus related lymphadenopathy,
      associated with diagnostic inclusion cells. Infected cells were confined to areas
      of monocytoid B cell hyperplasia in all cases whereas exceptionally observed in
      germinal centers. Because of their variable appearance, serial sectioning was
      frequently necessary to disclose their characteristic features. In all cases,
      immunohistochemistry using an anti-cytomegalovirus antibody was positive and
      revealed more infected cells than detected by morphology alone. Except for the
      endothelial cell, the nature of infected cells remained undetermined. An
      alteration of the antigenic expression as a consequence of cell infection might
      be responsible for immunohistochemistry failure in the cell characterization.

PMID- 9172614
TI  - [Tumor markers in the cytodiagnosis of thyroid nodules. Detection of dipeptidyl
      aminopeptidase IV (DAP IV) activity].
AB  - Dipeptidyl-aminopeptidase IV (DAP IV), an exopeptidase involved in T-cell
      activation is absent from normal thyroid tissue but highly expressed by malignant
      thyroid cells. It has been suggested to be a useful adjunct for the diagnosis of
      malignant thyroid tumors on fine needle aspirates (FNA). To assess this
      assumption DAP IV activity was demonstrated by histochemical staining on FNA
      performed on 102 thyroid nodules at the time of surgery (60 macrofollicular
      adenomas, 15 microfollicular adenomas. 7 Hashimoto's thyroiditis, 3 Graves'
      disease. 13 papillary carcinomas and 4 follicular carcinomas). A staining score
      based on the percentage of positive epithelial cells and staining intensity was
      established for each case and results were compared to histological diagnosis.
      Most cells in malignant tumors were deeply stained except in one case of
      papillary carcinoma. Null or very low scores resulting from light or medium
      staining of less than 40% of the cells were obtained in 78/85 benign nodules. In
      6 macrofollicular adenomas and in 1 case of thyroiditis staining score was as as
      high as in carcinomas. DAP IV staining was correlated to malignancy in all
      follicular tumours (4 malignant tumours were positive and 15 benign were
      negative). The sensitivity for diagnosis of malignancy was 94.1% and the
      specificity 91.7%. This study brings confirmation that DAP IV activity detection
      could be an useful adjunct to cytological examination for the distinction between
      benign and malignant thyroid nodules, especially in cases of follicular tumors.

PMID- 9172615
TI  - [Role of guided fine needle punction in the diagnosis of deep-seated Aids-related
      infections. Report of a case of hepato-nodal histoplasmosis].
AB  - A case of disseminated histoplasmosis diagnosed by fine needle aspiration biopsy
      is reported. The patient suffering from acquired immune deficiency syndrome
      (AIDS) had enlarged liver, spleen and mesenteric lymph nodes. Cytological smears
      prepared from a CT scan guided fine needle aspiration biopsy of one of the lymph
      node and the liver, showed numerous free or intrahistiocytic yeasts consistent
      with Histoplasma capsulatum. Yeasts and protozoars morphologically close to Histo
      plasma capsulatum are reviewed. The indications of fine needle aspiration biopsy
      for the diagnosis of infections in AIDS patients are emphasized. This method
      enables to send rapidly material for cultures and to start immediately an
      appropriate treatment.

PMID- 9172616
TI  - [Low-grade papillary adenocarcinoma of the endolymphatic sac. Report of three
      cases with immunohistochemical study].
AB  - Glandular tumors involving the mastoid and the middle ear are rare, and
      distinguishing between adenoma and adenocarcinoma remains difficult. Among these
      latter lesions, two distinct patterns are accepted. One of them, the papillary
      form takes a more aggressive course with wider regional spread and must be
      separated from the other type, the middle ear carcinoma. Its microscopic
      appearance and clinical course have been extensively described by Heffner who
      considered it as "low-grade adenocarcinoma of probable endolymphatic sac origin".
      A few cases have been associated with von Hippel-Lindau disease. Three cases of
      papillary adenocarcinoma of endolymphatic sac origin are reported. One concerned
      an isolated tumor, the two others were associated with von Hippel-Lindau disease.
      Their clinical, pathological and immunohistochemical data are presented.

PMID- 9172617
TI  - [Vestigial cysts of the anterior intestine of unusual localization. Report of two
      cases].
AB  - Bronchogenic cysts and enteric cysts both result from an aberration of
      development of the anterior gut. Their usual location is the mediastinum. The
      abdominal or retroperitoneal location of such cysts is rare and raises problems
      in terminology and pathogenesis. We report two cases of an unusual location of
      bronchogenic and enteric cysts. We also recall the criteria of diagnosis and the
      pathogenesis.

PMID- 9172618
TI  - [Risks of diagnostic errors in pathology research of post-abortion herpetic
      endometritis: limitations of immunohistochemistry in situ hybridization].
AB  - Endometrial Herpes-simplex infection is rare. Less than 10 cases have been
      reported. The impact of herpetic endometritis and abortion is not known, because
      of the scarcity of clinical and histological data. We present and discuss two
      cases of abortion with microscopic intranuclear inclusion of biotin, suggestive
      of herpetic endometritis. These inclusions were positively marked on
      immunohistochemistry, using anti-herpes antibodies. Similar results were obtained
      with in situ hybridization using biotin labeled probes (commonly used in some
      laboratories). But the normal accumulation of biotin in the endometrial cells of
      pregnant women diminishes the value of such results in gestational material. In
      fact the interaction between intranuclear endogenous biotin and the avidin-biotin
      peroxidase complex may explain the positive controls, performed without anti
      herpes antibodies. The biotin labeled probes may also explain the positive
      results of in situ hybridization. We strongly support the opinion that in
      pregnant women, the diagnosis of herpetic endometritis needs methodological
      precautions to avoid pitfall caused by endogenous biotin.

PMID- 9172619
TI  - [Scrotal panniculitis due to cold: a pseudo-tumoral lesion in the prepubertal
      child. Report of a case].
AB  - We reported a case of scrotal panniculitis in a 7 year-old boy after exposure to
      cold by swimming in cold sea water. Scrotal cold panniculitis is an unusual,
      confined to prepuberal patients. This entity must be known to avoid surgical
      exploration because injuries subside spontaneously within few weeks.

PMID- 9172620
TI  - [Splenic lymphoma with villous lymphocytes: morphologic, immunologic and
      molecular study. Report of three cases].
AB  - Splenic lymphoma with villous lymphocytes (SLVL) is a low grade
      lymphoproliferation characterized by a massive splenomegaly, an absence of
      lymphadenopathy and the presence in the peripheral blood of atypical B
      lymphocytes with hairy-cell appearance. We have studied the morphological,
      immunological and molecular characteristics of 3 cases of SLVL. SLVL presented on
      blood smears characteristic irregularities of the plasma membrane consisting in
      thin and short villi unevenly distributed. The main phenotype was CD5-, CD11c+,
      and CD25-, but individual SLVL cases can not be identified by using
      immunohistochemical criteria alone. Clonal rearrangements of the immunoglobulin
      heavy chain gene were found in all 3 cases and in one case presented a bcl2-JH
      rearrangement. SLVL are clonal B-cell lymphoproliferations and can be associated
      with t(14; 18) translocation.

PMID- 9172621
TI  - [Malignant granular cell tumor. Report of a clinico-pathologic case].
AB  - The authors report a case of malignant granular cell tumor present in right
      buttock of a 40 year-old male. The diagnosis of these very rare (less than 50
      cases reported in literature) and poor prognosis tumors is difficult. The
      diagnosis criteria of malignancy are reviewed regarding this clinical case and
      the literature.

PMID- 9172622
TI  - ["Metastatic" Crohn's disease of the penis].
AB  - Inflammatory genital cutaneous involvement of Crohn's disease is a rare
      complication. In a 23 year old man, who had colonic Crohn's disease treated by
      colectomy 3 years earlier, a phimosis revealed a penile localisation of Crohn's
      disease. "Metastatic" locations of Crohn's disease are defined by granulomas
      sitting at a distance from the injured bowel. Their clinical manifestations are
      misleading and their course is independent of the digestive disease. In our
      patient, after failure of classical therapy, cyclosporin A permitted a slow
      regression.

PMID- 9172623
TI  - [Pancreatic and duodenal somatostatinoma. Two clinico-pathologic entities].
AB  - Somatostatinomas are endocrine tumors with predominant secretion of somatostatin.
      The majority occur in the pancreas and the duodenum. However, distinctive clinico
      pathologic features are reported for both of them. The features of pancreatic
      somatostatinomas are a larger size, a more frequent clinical expression, a female
      predominance and a poorer prognosis. Duodenal somatostatinomas are characterized
      by psammoma bodies at histologic examination. We report here two cases of
      pancreatic and ampullary somatostatinomas, focusing on the main diagnostic
      problems and on the characteristics of each tumoral localization.

PMID- 9172624
TI  - [Gastric lesion revealed by a persistent hiccup].

PMID- 9172625
TI  - [An unusual thyroid "nodule"].

PMID- 9172626
TI  - [Antigenic retrieval using a pressure cooker].
AB  - This technical note describes antigen retrieval procedures using a pressure
      cooker. These procedures are perfectly adapted to routine immunohistochemistry
      and improve the overall quality of immunostaining.

PMID- 9172627
TI  - [Cultivation of human keratinocytes of mucous membranes of the upper
      aerodigestive tract].
AB  - BACKGROUND: Cultivation of benign epithelial cells under standardized conditions
      is of major interest in many fields of clinical and basic research. A modified
      fast and simple method for isolation, growth and passage of epidermal cells has
      been developed with consideration given to the complex environment of the upper
      aerodigestive tract. METHODS: Normal human mucosa of the upper aerodigestive
      tract was taken from 15 patients (4-73 years) during diagnostic and therapeutic
      operations. The epithelium could be separated easily from the mucosa after
      incubation the biopsies in disease over night. Subsequently, keratinocytes were
      isolated enzymatically by dissociation of epidermal sheets in trypsin, resulting
      a suspension of highly proliferating keratinocytes without contaminating
      fibroblasts (2 x 10(6) keratinocytes/biopsy). The cells were washed several times
      in fresh fetal calf serum before they were plated in untreated culture flasks.
      The keratinocytes were cultivated in serum-free medium supplemented with
      epidermal growth factor, bovine pituitary extract, amphotericin B, and
      penicillin/ streptomycin. RESULTS: An average plating efficiency of 60% in
      primary cultures and 85% in subcultures was obtained. Passaging was possible
      every 10-13 days when keratinocytes reached sufficient confluency. The cells
      could be subcultured up to eight times (lifespan of 120 days), and exhibited the
      typical epithelial morphology during cultivation. CONCLUSION: Because of the
      modified pretreatment of the keratinocytes before plating, this culturing
      protocol for keratinocytes derived from the upper aerodigestive tract enables
      easy and fast cultivation of keratinocytes, further simplifying currently
      available methods.

PMID- 9172628
TI  - [Experiences with upper eyelid gold implantation in facial paralysis].
AB  - BACKGROUND: A lagophthalmus following facial nerve palsy is not only a cosmetic
      problem, but can also cause serious complications to the cornea, such as
      ulceration and perforation. A passive eyelid closure can be achieved by the
      implantation of a gold weight in the upper eyelid. METHODS: Within five years we
      performed 21 implantations of gold weights in patients with facial nerve palsy.
      RESULTS: In 19 patients (90%) good eyelid closure was achieved. In three patients
      the gold weight was removed for the following reasons: remission of paralysis,
      foreign body sensation, and wound infection. CONCLUSIONS: The insertion of an
      eyelid goldweight in the upper eyelid in patients with established facial palsy
      is an effective method of reducing the incidence of discomfort to the eye and
      corneal complications. The insertion is simple and performed under local
      anaesthesia, and is easily reversed or revised if necessary.

PMID- 9172629
TI  - [Differential diagnosis of tumorous space-occupying lesions of the parotid gland:
      angiolymphoid hyperplasia with eosinophilia and Kimura disease].
AB  - BACKGROUND: Subcutaneous mass lesions of the head and neck are common in
      angiolymphoid hyperplasia with eosinophilia (ALHE) as well as in Kimura's
      disease, most often in a periauricular location in young and middle aged adults.
      Often these benign angioproliferative lesions of unknown etiology will be
      misdiagnosed as parotid tumors although the majority are paraglandular. Whereas
      ill-defined lesions involving the parotid gland are frequently observed in
      Kimura's disease, only one case of intraparotid ALHE is reported in the
      literature. CASE REPORT: To this we add one further case: a 24-year-old man with
      a solid and well displaceable tumor of the left preauricular region. At
      ultrasound and intraoperatively we found a well demarcated tumor with high
      central vascularization surrounded by multiple networks of veins. One larger
      artery entered the lesion directly, visible as vascular structure on the cut
      surface. This blood vessel may have represented a vascular pattern (3 mm in
      diameter) that was identified as an artery by flow velocity measurement at duplex
      sonography. Histopathologically we saw the characteristic features of ALHE:
      numerous capillary proliferations showing prominent epithelioid endothelia cells
      with typical "hop nail" appearance, focal lympho-plasmacellular infiltrations and
      many eosinophils. The most conspicuous microscopic feature was a large thick
      walled artery with total occlusions of the lumen that partially corresponded to
      duplex sonographic and macroscopic findings. CONCLUSION: In our opinion, this may
      be indicative of a primary arterial disorder with secondary vascular
      proliferation and chronic inflammation. The treatment of choice is local excision
      with a safe margin of healthy tissue, since insufficient removal can result in
      recurrence.

PMID- 9172630
TI  - [History of the tuning fork. I: Invention of the tuning fork, its course in music
      and natural sciences. Pictures from the history of otorhinolaryngology, presented
      by instruments from the collection of the Ingolstadt German Medical History
      Museum].
AB  - BACKGROUND: G. Cardano, physician, mathematician, and astrologer in Pavia, Italy,
      in 1550 described how sound may be perceived through the skull. A few years later
      H. Capivacci, also a physician in Padua, realized that this phenomenon might be
      used as a diagnostic tool for differentiating between hearing disorders located
      either in the middle ear or in the acoustic nerve. The German physician G. C.
      Schelhammer in 1684 was the first to use a common cutlery fork in further
      developing the experiments initiated by Cardano and Capivacci. For a long time to
      come, however, there was no demand for this in practical otology. THE INVENTION
      OF THE TUNING FORK: The tuning fork was invented in 1711 by John Shore, trumpeter
      and lutenist to H. Purcell and G.F. Handel in London. A picture of Handel's own
      tuning fork, probably the oldest tuning fork in existence, is presented here for
      the first time. There are a number of anecdotes connected with the inventor of
      the tuning fork, using plays on words involving the name Shore, and mixing up
      pitch-pipe and pitchfork. Some of these are related here. The tuning fork as a
      musical instrument soon became a success throughout Europe. THE PHYSICS OF THE
      TUNING FORK: The German physicist E. F. F. Chladni in Wittenberg around 1800 was
      the first to systematically investigate the mode of vibration of the tuning fork
      with its nodal points. Besides this, he and others tried to construct a complete
      musical instrument based on sets of tuning forks, which, however, were not widely
      accepted. J. H. Scheibler in Germany in 1834 presented a set of 54 tuning forks
      covering the range from 220 Hz to 440 Hz, at intervals of 4 Hz. J. Lissajous in
      Paris constructed a very elaborate tuning fork with a resonance box, which was
      intended to represent the international standard of the musical note A with 435
      vibrations per second, but this remained controversial. K. R. Koenig, a German
      physicist living in Paris, invented a tuning fork which was kept in continuous
      vibration by a clockwork. H. Helmholtz, physiologist in Heidelberg, in 1863 used
      sets of electromagnetically powered tuning forks for his famous experiments on
      the sensations of tone. Until the invention of the electronic valve, tuning forks
      remained indispensible instruments for producing defined sinusoidal vibrations.
      The history of this development is presented in detail. The diagnostic use of the
      tuning fork in otology will be described in a separate article.

PMID- 9172631
TI  - [Speech audiometry with logatomes].
AB  - BACKGROUND: Logatomes are nonsense syllables used for analyzing the confusion of
      phonemes by hearing impaired listeners. They can provide a precise
      differentiation of phonemic confusions which may be useful in the exact
      adjustment of programmable hearing aids. METHODS: In this study, two lists of
      logatomes with 108 three-sound combinations with a structure of consonant-vowel
      consonant (c-v-c) and vowel-consonant-vowel (v-c-v) were recorded on a compact
      disk. Twenty normally hearing adults and 28 patients with a sensorineural hearing
      loss were tested at a comfortable listening level of about 25 +/- 5 dB above the
      mean audiometric thresholds at 0,5. 1,0 and 2,0 kHz. An index of reduction of
      speech perception was calculated. RESULTS: A significant relationship between
      reduction of logatome perception and pure-tone audiometric thresholds at 1,2,3,
      and 4 kHz was demonstrated. Moreover, it was possible to distinguish between
      different groups of hearing impairment. CONCLUSIONS: The logatome test helps to
      analyze specific effects that hearing loss can have on the recognition of
      acoustic speech signals. The logatome test may become a valuable addition to
      speech audiometric tests with further standardization.

PMID- 9172632
TI  - [Nasal hyperreactivity. Allergic rhinitis and differential diagnoses--consensus
      report on pathophysiology, classification, diagnosis and therapy].

PMID- 9172633
TI  - [Endonasal coagulation of the sphenopalatine artery in severe posterior
      epistaxis].
AB  - BACKGROUND: Until a few years ago the surgical method of choice in treating
      uncontrollable nosebleeds from the posterior part of the nose was the transantral
      ligation of the maxillary artery as described by Seiffert (Caldwell-Luc
      approach). We introduce a surgical method to expose and coagulate the
      sphenopalatine artery through an endonasal approach. METHOD: The middle meatus of
      the nose is exposed with a self supporting nasal speculum under the microscope
      (focus: 300 mm) and the maxillary sinus is opened through the posterior
      fontanelle. The medial wall of the maxillary sinus is removed from this opening
      to its end. Three to five millimeters posterior to this site, the foramen
      sphenopalatinum is exposed. The osseous lateral margin of the foramen is resected
      with the drill and the fossa pterygopalatina is thereby opened from the nose. The
      sphenopalatine artery can be exposed all the way to its origin from the maxillary
      artery and then coagulated. RESULTS: Thirty-one patients with severe epistaxis
      have been operated by this method since October 1993. No postoperative
      complications were observed in any cases. Thirty patients have had no further
      nosebleed since than (average follow-up 22.9 months). In one case of a patient
      with renal insufficiency a nose bleed occurred 15 day postoperatively following
      dialysis. It was controlled by ligation of the anterior ethmoid artery and of the
      peripheral branches of the external carotid artery. CONCLUSION: The endonasal
      coagulation of the sphenopalatine artery is the safest method to control bleeding
      from the posterior parts of the nose. It can be performed by anyone who is
      familiar with endonasal surgery. The disadvantages of the transanteral ligation
      of the maxillary artery as described by Seiffert (Caldwell-Luc approach, ligation
      not sufficiently peripheral) are avoided. The only competing method would be the
      embolization of the sphenopalatine artery which can not be applied in every
      hospital and which has a higher complication and failure rate. Since October 1993
      when this method was introduced no additional bellocq tamponade was required in
      epistaxis.

PMID- 9172634
TI  - [Endovascular embolization treatment for intractable epistaxis].
AB  - BACKGROUND: Intractable epistaxis has been treated with surgical intervention for
      many years, including ligation of the internal maxillary artery. As an
      alternative approach, endovascular therapy has gained increased acceptance. The
      purpose of our study was to evaluate the efficacy and safety of endovascular
      treatment of untractable epistaxis. METHODS: Embolotherapy was performed in 26
      patients. The indication for embolization was persistent epistaxis even after
      anterior and posterior nasal packing. In all but two patients, who required
      general anesthesia, the procedure was performed in local anesthesia. Endovascular
      embolization of the internal maxillary artery was performed by using
      microcatheters, which were introduced intraarterially. Particulate embolic agents
      were used in all but one patient, who was treated by means of minicoils. RESULTS:
      The embolization of the territory of the internal maxillary artery was possible
      in all cases, the technical success rate was 96%, the clinical success rate was
      100%. No complications were encountered. Because of an acute recurrent bleeding
      in one case, a second embolization was performed. No delayed hemorrhages were
      noted. CONCLUSIONS: Endovascular embolotherapy seems to be an excellent, safe,
      and less invasive alternative to surgery in patients with intractable epistaxis.

PMID- 9172635
TI  - [Parastomal tumors after laryngectomy: etiology and therapy].
AB  - BACKGROUND: Parastomal neoplasm after total laryngectomy for laryngeal carcinoma
      represents an extremely serious complication and one of the most formidable
      therapeutic problems encountered by the head and neck surgeon. Studies about the
      etiology of parastomal neoplasm have been controversial. The factors most
      strongly implicated in parastomal neoplasm have been recurrence spawned by
      metastases to deep cervical lymph nodes, undetected neoplasm at the margin of the
      laryngectomy resection, neoplastic cell implantation by pre-operative
      tracheotomy, and the development of an additional primary. PATIENTS: To clarify
      the controversial aspects of parastomal neoplasm etiology, a systematic analysis
      of parastomal neoplasm after laryngectomy was performed using data from 10
      patients who developed parastomal neoplasm. RESULTS: Parastomal neoplasm occurred
      in 7.9%. The tumor site of the primary laryngeal carcinoma was found in 9/10
      cases in the subglottic, supraglottic, or transglottic area. These tumor sites
      correlate with areas of a lymphatic vessel concentration and an increase of
      intralaryngeal lymphatic drainage. In average the parastomal neoplasms appear
      10.3 months after the laryngectomy. Therapy was unsuccessful in spite of
      extensive surgical interventions. CONCLUSIONS: If the laryngeal carcinoma was
      resected with margins of healthy tissue, lymphatic metastasis to the pretracheal
      and paratracheal cervical lymph nodes is the probable cause of parastomal
      neoplasm. This could be the consequence of the continuous lymphatic drainage
      between the supraglottic and subglottic area with a midline crossing and an
      lymphatic outlet to the pretracheal and paratracheal cervical lymph nodes. The
      cervical metastasis formation cannot be detected due to the limitations in the
      assessment of small lymph nodes and the inability to ascertain with confidence
      the presence or absence of metastasis in any one lymph node in ultrasonography,
      computed tomography, and magnetic resonance imaging and due to the limitations in
      the removal of lymph nodes in the pretracheal and paratracheal area by means of a
      functional or radical neck dissection. The method of treatment should be in cases
      of a subglottic or a supraglottic laryngeal carcinoma an ipsilateral and
      contralateral pretracheal and paratracheal lymph node removal in combination with
      the laryngectomy.

PMID- 9172636
TI  - [Proliferative potential of nasal septum chondrocytes for in vitro culture of
      cartilage transplants].
AB  - BACKGROUND: Recent developments in the field of tissue engineering provide novel
      approaches in tissue repair and reconstructive surgery using the patients own
      cells. Isolated chondrocytes form new cartilage when seeded in appropriate
      scaffolds. Usually the number of cells from a cartilage biopsy is not sufficient.
      The present study investigates the potential of cell amplification of human nasal
      chondrocytes in monolayer culture. METHODS: Nasal cartilage cells from seven
      healthy patients with age between 16 and 60 years were enzymatically isolated
      with collagenase and hyaluronidase. Subsequently, cells were seeded in 75 cm2
      culture flasks. After confluency, cultures were trypsinized, counted, and again
      seeded at a concentration of 5 x 10(4) cells/ml. Dulbecco's MEM supplemented with
      10% FCS was used as culture medium. RESULTS: After enzymatic digest, an average
      of 5 x 10(5) cells per patient were isolated. At least 85% of the cells were
      vital. Within four to eight weeks, the cells number was increased 10(3) to 10(5)
      fold. No correlation between the proliferative activity and the age of the
      patient was observed in this study. DISCUSSION: The observed increase in cell
      number resembles about 10 to 20 cell doublings. Although the doubling time
      appears to be longer during the second month, no definite limit of proliferative
      activity was seen during the time of study. Proliferating chondrocytes in
      monolayer lose their tissue-specific phenotype. For the de novo formation of
      cartilage transplants, redifferentiation of the expanded cells has to be
      stimulated. CONCLUSION: This study shows that human nasal chondrocytes can be
      expanded sufficiently in monolayer for the engineering of autologous cartilage
      transplants.

PMID- 9172637
TI  - [Critical evaluation of the new inhalational anesthetics desflurane and
      sevoflurane].
AB  - New anaesthetic agents are being continuously developed to find the ideal agent.
      The most commonly used inhaled anaesthetic in adults is isoflurane and in
      children halothane. The need for, and the value of the new agents desflurane and
      sevoflurane depend on a comparison of the properties of a theoretically ideal
      agent with those of isoflurane, halothane and the new agents. Therefore, the
      following topics are discussed in the overview: pharmacokinetic properties,
      recovery parameters, mask induction in adults, paediatric anaesthesia,
      metabolism, stability in carbon dioxide absorbents and cardiovascular effects.
      Desflurane and sevoflurane may be considered a step toward the ideal inhalational
      agents. Both possess the advantage of rapid recovery from surgical anesthesia.
      Desflurane has a major advantage over sevoflurane: it is not biotransformed nor
      does it interact with carbon dioxide absorbents. However, desflurane is
      associated with troublesome cardiovascular stimulation involving tachycardia and
      both pulmonary and systemic hypertension. Sevoflurane appears to be advantageous
      for three reasons: firstly, because of its pleasant odour and consequent
      suitability for induction by inhalation, particularly in paediatric anaesthesia;
      secondly, it can be used with currently employed vaporizers, and thirdly,
      surgical demands can be met by lower doses, because its potency is higher.

PMID- 9172638
TI  - [Patient preparation and premedication--legal aspects].
AB  - The legal demands concerning the methods of treatment required of an anaesthetist
      are determined by the quality of the specialist and the professional standard. As
      long as there is no premedication procedure which is generally considered
      superior to all others, the anaesthetist can freely choose the procedure, while
      carefully considering benefits and risks on the basis of the individual
      circumstances of each case. The patient must be informed about the anaesthesia
      before premedication since the latter inhibits his/her ability to make decisions.

PMID- 9172639
TI  - [Ventilation modes and strategies in intensive care medicine].
AB  - Advances in ventilator technology and recent findings in pathophysiological
      mechanisms have resulted in a remarkable decrease in classical volume controlled
      and pressure controlled ventilation modes as treatment for severe acute
      respiratory insufficiency. New modes of ventilatory support enabling and
      encouraging patients' spontaneous breathing, such as Biphasic Positive Airway
      Pressure (BIPAP) and Airway Pressure Release Ventilation (APRV), make it possible
      to adapt ventilatory support better and more easily to suit patients' needs than
      conventional modes of controlled ventilation. Preservation and support of
      patients' spontaneous breathing improves pulmonary gas exchange and reduces
      stress imposed by mechanical ventilation. The 'invasiveness' of mechanical
      ventilation is reduced and patients' comfort is less disturbed. Through this, the
      need for sedation and analgesia is considerably reduced and this may minimize
      systemic side-effects and complications from analgo-sedation and mechanical
      ventilation. The drugs should be administered in an adequate, individually
      adapted manner. Routinely-ordered and fixed combinations of drugs administered
      continuously are not adequate adequate as they further carry the risk of
      overdosing a different single drug with the corresponding side-effects
      (depression of respiratory drive, gut motility, etc.).

PMID- 9172640
TI  - Comparison of the structures of the metal-thiolate binding site in Zn(II)-,
      Cd(II)-, and Hg(II)-metallothioneins using molecular modeling techniques.
AB  - The first fully energy-minimized structures for a series of structurally related
      metal complexes of the important mammalian metal binding protein metallothionein
      are described. The structures were calculated based on structural information
      obtained from existing spectroscopic and crystallographic data, and minimized
      using molecular mechanics (MM2) techniques. A two domain structure, with
      stoichiometries of M(II)3-(Scys)9 and M(II)4-(Scys)11 where M = zinc(II),
      cadmium(II), and mercury(II), was assembled and minimized. The resultant three
      dimensional structure closely resembled that of rat liver Cd5Zn2-MT 1 obtained by
      analysis of x-ray diffraction data [A. H. Robbins, D.E. McRee, M. Williamson, S.
      A. Collett, N. H. Xuong, W. F. Furey, B. C. Wang and C. D. Stout, J. Mol. Biol.
      221, 1269-1293 (1991)]. Minimized structures for Zn7-MT, Cd7-MT, and Hg7-MT are
      reported. Deep crevices that expose the metal-thiolate clusters are seen in each
      structure. However, for the mercury-containing protein, much of the mercury
      thiolate structure is visible and it is proposed that this provides access for
      extensive interaction between solvent water molecules and the mercury(II),
      resulting in the observed distortion away from tetrahedral geometry for Hg7-MT.
      Volume calculations are reported for the protein metallated with 7 Zn(II),
      Cd(II), or Hg(II). A series of structural changes calculated for the step-wise
      isomorphous replacement of Zn(II) by Cd(II) and Hg(II) in the Zn4S11 alpha domain
      are shown.

PMID- 9172641
TI  - Recognition of promoter DNA by subdomain 4.2 of Escherichia coli sigma 70: a
      knowledge based model of -35 hexamer interaction with 4.2 helix-turn-helix motif.
AB  - In Escherichia coli, subdomains 2.4 and 4.2 of the primary transcription factor
      sigma 70 are the most highly conserved regions and are responsible for the
      recognition of -10 and -35 promoter elements respectively. Mutational studies
      provide evidence to this end and indicate that the side chains of subdomain 4.2
      make specific contacts with the nucleotides at -35. Subdomain 4.2 is highly
      conserved among group-1 sigma factors and is strongly homologous to the classical
      helix-turn-helix (HTH) motif shared by bacteriophage lembda cl, Cro, the CAP
      protein and other homeodomain proteins, suggesting that sigma factor also belongs
      to the HTH class of proteins. In this study, a single point mutation of the
      conserved hydrophobic residue valine at position 576, in the 4.2 subdomain
      results in a mutant that is transcriptionally inefficient although
      conformationally similar to wild-type sigma. The mutant sigma, like wild-type,
      migrates as a 87 kDa protein on SDS gels and has 50% helicity. However,
      transcription at "extended -10 promoter' by RNA polymerase containing mutant
      sigma 70-V576G, synthesized appreciable amount of RNA product, when compared with
      that generated by sigma 70-W434G, a mutation in -10 DNA binding domain. A model
      of HTH motif for the conserved 20 residue region of 4.2 domain of E. coli sigma
      70 as well as its mutant sigma 70-V576G and sigma 70-V576T were constructed based
      on five other homologous HTH motifs from DNA-protein complexes for which X-ray or
      NMR structure is available. A B-DNA structure was designed for -35 region using
      sequence dependent base pair parameters. The modeled HTH structure was docked
      into the major groove formed by the -35 hexamer DNA using the DNA-recognition
      rules and amino acid-nucleotide base contact information of homologous DNA
      protein complexes. Analysis of the residue contact information of the model was
      tested and found to have good agreement with the experimental reports.

PMID- 9172642
TI  - Solution structure of the HIV protease inhibitor acetyl-pepstatin as determined
      by NMR and molecular modeling.
AB  - The structure of acetyl-pepstatin has been investigated in solution by two
      dimensional NMR spectroscopy and molecular modeling. The analysis of DQFCOSY,
      TOCSY and NOESY spectra lead to a full assignment of the -NMR signals both in
      DMSO-d6 and in TFE-d3:H2O 1:1. Interproton distances, dihedral angles and
      exchanger regimes of NH or OH protons were derived from ROESY connectivities,
      coupling constants and temperature dependences of the chemical shifts,
      respectively. Molecular modeling using the NMR distance and dihedral angle
      constraints obtained in DMSO-d6 yielded a model showing a well-defined structure
      for the N-terminal segment Ac-1 to Sta-4, but a flexible structure for the C
      terminal segment. The structure was less defined in TFE-d3:H2O 1:1 and 13C T1
      measurements are indicative of higher mobility. Comparison of the NMR-determined
      solution structure of acetyl-pepstatin with its crystal structure when bound to
      HIV-1 protease shows that the conformation is more extended in the complex as a
      result of intermolecular interactions.

PMID- 9172643
TI  - Synthesis and FTIR conformational studies of peptides from the basic region of c
      Jun: a critical analysis on the basis of CD and NMR data.
AB  - The peptide (35 residues) corresponding to the basic subdomain (bSD) of c-Jun
      (residues 252-281) and its fragments NP (N-terminal peptide, 1-19) and CP (C
      terminal peptide, 16-35) were synthesized in stepwise solid-phase using the tert
      butyloxycarbonyl/benzyl strategy. In a previous paper, we have shown that during
      its binding to the DNA site CRE (cAMP-responsive element) the bSD structure was
      converted into alpha-helix from an initial random coil conformation [Krebs, D.,
      Dahmani, B., El Antri, S., Monnot, M., Convert, O., Mauffret, O., Troalen, F. &
      Fermandjian, S. Eur. J. Biochem. 231, 370-380 (1995)]. Our results suggested both
      a high flexibility and a helical potential in bSD, these two properties seeming
      crucial for the accommodation of the basic subdomain of c-Jun to its specific DNA
      targets. In this work, we assessed the conformational variability of bSD through
      the study of the secondary structures of its NP and CP fragments in
      trifluoroethanol (TFE)/2H2O mixtures, using Fourier transform infrared (FTIR)
      spectroscopy. The IR results were critically analyzed in light of our previously
      reported circular dichroism (CD) and NMR data [Krebs, D., Dahmani, B., Monnot,
      M., Mauffret, O., Troalen, F. & Fermandjian, S. Eur. J. Biochem, 235, 699-712
      (1996)]. Upon addition of TFE, the relative areas of the seven components of the
      amide I. band (1700-1620 cm-1) reflected the conversion of a large amount of
      random coil conformation into alpha-helix for the two fragments and bSD. This
      effect was accompanied by more subtle variations of the less populated
      structures, in agreement with the results of CD and NMR experiments. The IR
      results stipulated the conservation of the parent bSD secondary structures in
      both fragments; however, NP and CP peptides did not display similar random-to
      alpha-helix stabilization pattern upon additions of TFE to aqueous solutions. The
      profile from CD signal at 222 nm was found sigmoidal for NP and almost linear for
      CP, while that corresponding to the parent peptide bSD was just in between those
      of its fragments. Thus, the present study confirms the high flexibility and helix
      propensity of the c-Jun basic subdomain and suggests that the N- and C-terminal
      parts of the peptide do not follow the same random-to-helix conversion profile
      during their complexation with DNA.

PMID- 9172644
TI  - A molecular mechanics and database analysis of the structural preorganization and
      activation of the chromophore-containing hexapeptide fragment in green
      fluorescent protein.
AB  - We propose that heterologous posttranslational chromophore formation in green
      fluorescent protein (GFP) occurs because the chromophore-forming amino acid
      residues 65SYG67 are preorganized and activated for imidazolinone ring formation.
      Based on extensive molecular mechanical conformational searching of the precursor
      hexapeptide fragment (64FSYGVQ69), we suggest that the presence of low energy
      conformations characterized by short contacts (approximately 3 A) between the
      carbonyl carbon of Ser65 and the amide nitrogen of Gly67 accounts for the initial
      step in posttranslational chromophore formation. Database searches showed that
      the tight turn required to establish the key short contact is a unique structural
      motif that is rarely found, except in other FSYG tetrapeptide sequences.
      Additionally, ab initio calculations demonstrated that an arginine side chain can
      hydrogen bond to the carbonyl oxygen of Ser65, activating this group for
      nucleophilic attack by the nearby lone pair of the Gly67 amide nitrogen. We
      propose that GFP chromophore-formation is initiated by a unique combination of
      conformational and electronic enhancements, identified by computational methods.

PMID- 9172645
TI  - Segmented structure of separate and transposable DNA and RNA elements as
      suggested by their size distributions.
AB  - A collection of about 1000 different eukaryotic and prokaryotic DNA mobile and
      separate elements is compiled from literature-transposons, plasmids,
      extrachromosomal circular DNA, insertion sequences, as well as viral genomes and
      separate genome segments. Only small elements are collected, upto 2000 base
      pairs. Analysis of the sequence length distributions of the elements reveals that
      certain sizes are clearly preferred, namely those which correspond to multiples
      of about 345 bp in eukaryotes and multiples of about 210 bp in prokaryotes. This
      provides additional evidence in support of the theory (1) that segmented
      structure is characteristic of not only protein-coding sequences (2) but rather
      of genomes in general. In particular, it confirms the prediction (1) that mobile
      and separate elements would also be segmented.

PMID- 9172646
TI  - The study of possible A and B conformations of alternating DNA using a new
      program for conformational analysis of duplexes (CONAN).
AB  - A new program, CONAN has been designed for CONformational ANalysis of
      oligonucleotide duplexes with natural and modified bases. It allows to model both
      regular DNA fragments with different types of symmetry and irregular ones
      including bends, junctions, mismatched pairs and base lesions. Computations and
      minimization of the energy are performed in a space of internal structural
      variables chosen to build start structure easier and conveniently analyze the
      results obtained. These internal structural variables determine mutual base-base
      and base-sugar arrangement and sugar puckering. The analytical closure procedure
      is applied both to sugar rings and to backbone fragments between adjacent sugars.
      For more effective energy minimization, analytical gradient is calculated. The
      CONAN was applied to the search for low-energy conformations of poly(dA
      dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) duplexes. Extended regions of low
      energy A and B conformations are revealed and characterized. These regions
      contain structures with different relative values of helical twist, tau, for pur
      pyr and pyr-pur steps, namely, conformations with tau (pur-pyr) > tau (pyr-pur)
      and with tau (pur-pyr) < tau (pyr-pur). Two types of sugar puckering were found
      for B-form low-energy conformations, the first type with all C2'-endo sugar
      residues and the second one - with C2'-endo purines and O1'-endo pyrimidines. The
      calculated conformations are compared with X-ray diffraction data for crystals
      and fibers and NMR data for solution.

PMID- 9172647
TI  - Theoretical studies using an ab initio and molecular modelling combination method
      on the binding of sequence recognition altered bis-benzimidazoles to the minor
      groove of DNA.
AB  - Ab initio calculations (Hartree-Fock) using the 3-21G and the STO-3G Gaussian
      basis sets were performed on synthetic analogues of the minor groove binding bis
      benzimidazole Hoechst 33258 designed to exhibit altered sequence recognition.
      Geometry optimized conformations, energies and distribution of electrostatic
      charges within the molecule were derived. The binding of the optimized
      conformations of the drug to both alternating and non-alternating (AT)n and (GC)n
      sequences were studied.

PMID- 9172648
TI  - Hydrated water molecules of pyrimidine/purine/pyrimidine DNA triple helices as
      revealed by FT-IR spectroscopy: a role of cytosine methylation.
AB  - Hydrated water molecules of pyrimidine/purine/pyrimidine DNA hairpin triplex was
      studied by a comparison of triplex (CC.AG6) formed by a host oligodeoxypyrimidine
      of 5'-d(TC)3T4(CT)3(CC) with a target hexadeoxypurine 5'-d(AG)3(AG6) strand and
      by triplexes (MM.AG6, MC.AG6, and CM.AG6) formed by oligonucleotides with the
      exact sequences as above except 5-methylcytosine replaced all (MM), 5' end half
      (MC), and 3' end half (CM) cytosine bases in CC via FT-IR spectroscopy in
      hydrated film. Results revealed that: (i) all these triplexes have a similar
      hydration pattern, in which water molecules probably bound in the N7 sites of
      adenines and guanines in the Crick-Hoogsteen groove, and to the methyl group of
      thymidines in the Watson-Hoogsteen groove. There are also some bound water
      molecules found at the O2 sites of thymines in both Watson-Crick and Crick
      Hoogsteen grooves. (ii) In the CC.AG6 triplex the S-type sugars are always
      dominant in all hydrated states, whereas in MM.AG6 triplex the relative
      population of the N-type sugars is very close to that of the S-type between 86%
      and 66% of humidity. Furthermore, the sugar conformation in two partially
      modified triplexes (CM.AG6, and MC.AG6) are dominant by the N-type at lower
      humidity. This phenomenon might reflect that the degree of bound water varies
      among the binding sites of bases. (iii) The effect of introducing a methyl group
      on cytosine is to generate a spine of hydrophobic region in MM (MC and MC). The
      enlarging hydrophobic area not only increase the stability in solution, and also
      the stability in sodium hydrated films of the pyrimidine/purine/pyrimidine
      hairpin triplexes.

PMID- 9172649
TI  - Mg2+ dependence of the structure and thermodynamics of wheat germ and lupin seeds
      5S rRNA.
AB  - The formation and stability of structural elements in two 5S rRNA molecules from
      wheat germ (WG) and lupin seeds (LS) as a function of Mg2+ concentration in
      solution was determined using the adiabatic differential scanning
      microcalorimetry (DSC). The experimentally determined thermodynamic parameters
      are compared with calculations using thermodynamic databases used for prediction
      of RNA structure. The 5S rRNA molecules which show minor differences in the
      nucleotide sequence display very different thermal unfolding profiles (DSC
      profiles). Numerical deconvolution of DSC profiles provided information about
      structural transformations that take place in both 5S rRNA molecules. A
      comparative analysis of DSC data and the theoretical thermodynamic models of the
      structure was used to establish a relationship between the constituting
      transitions found in the melting profiles and the unfolding of structural domains
      of the 5S rRNA and stability of its particular helical elements. Increased
      concentrations of Mg2+ ions induces additional internal interactions stabilising
      5S rRNA structures found at low Na+ concentrations. Observed conformational
      transitions suggest a structural model in which the extension of helical region E
      dominates over the postulated tertiary interaction between hairpin loops. We
      propose that helix E is stabilised by a sequence of non-standard pairings
      extending this helix by the formation of tetra loop e and an almost total
      reduction of loop d between helices E and D. Two hairpin structures in both 5S
      rRNA molecules: the extended C-C' and the extended E-E'-E" hairpins appear as the
      most stable elements of the structure. The cooperativity of the unfolding of
      helixes in these 5S rRNA molecules changes already at 2 mM Mg2+.

PMID- 9172650
TI  - Vibrational analysis of phosphorothioate DNA: II. The POS group in the model
      compound dimethyl phosphorothioate [(CH3O)2(POS)]-.
AB  - The results of Raman and Infrared (IR) spectroscopic investigations on the
      vibrational modes of dimethyl phosphorothioate (DMPS) anion, [(CH3O)2(POS)]-, are
      reported. Ab initio calculations of the vibrational modes, the IR and Raman
      spectra and the interatomic force constants of DMPS were performed. A normal mode
      calculation was performed and the results were used to calculate the potential
      energy distribution for the vibrational modes. This analysis shows that in DMPS
      the P-S stretching mode has a frequency of about 630 cm-1 and an angle bending
      mode involving the sulfur atom has a frequency of about 440 cm-1. The proposed
      vibrational mode assignments will serve as marker bands in the conformational
      studies of phosphorothioate oligonucleotides which play a central role in the
      novel antisense therapeutic paradigm.

PMID- 9172651
TI  - Internal DNA modes below 25 cm-1: a resonance Raman spectroscopy observation.
AB  - The first resonance Raman scattering observation of the low-frequency (LF) region
      (below 40 up to 12 cm-1) of DNA motions is presented. Since the concentration of
      the studied DNA solution was very low (1 mg/ml), the spectra features reflect
      internal vibrations of the macromolecule. The decomposition of the spectra into
      Lorentzians clearly indicate three intrahelical DNA modes: the corresponding
      peaks are located at the frequencies 16, 19, and 23 (+/- 1) cm-1. This result is
      in agreement with our quasi-continuity model of the LF B-form DNA dynamics (V.
      Lisy, P. Miskovsky and P. Schreiber, J. Biomol. Struct. Dyn. 13, 707 (1996)). The
      fit of the experimental frequencies to the theory, using the Genetic Algorithms
      approach, allowed us to make some conclusions about the model force constants
      which could be found by independent conformational energy calculations. Possible
      positions of five lowest-frequency DNA peaks, predicted by the model, are
      discussed.

PMID- 9172652
TI  - Two isoflavones from the bark of Petalostemon purpureus.

PMID- 9172653
TI  - Findings of scientific misconduct.

PMID- 9172654
TI  - Depression in older people.

PMID- 9172655
TI  - Ordinary people, extraordinary problems. Interview by Ian McMillan.

PMID- 9172656
TI  - "Streptococcus milleri" strains exhibit not gliding motility but sliding.

PMID- 9172657
TI  - Spontaneous regression in angiocentric T-cell lymphoma.

PMID- 9172658
TI  - British Connective Tissue Society Meeting. Physical regulators of cell metabolism
      and tissue function. Oxford, 26-27 September 1996. Abstracts.

PMID- 9172659
TI  - Periodicity of Eating and Human Health. Proceedings of a meeting. Paris, France,
      21-23 November 1996.

PMID- 9172660
TI  - [Hydrocalicosis caused by a large renal artery aneurysm].
AB  - Rupture and development of hypertension represent frequent complications of renal
      artery aneurysms. We report the case of a 27-year-old patient with pain in the
      region of the right kidney due to a large renal artery aneurysm. This aneurysm
      induced partial, obstructive hydrocalicosis. The aneurysm was clearly
      differentiated from the dilated calices by color Doppler sonography and contrast
      enhanced spiral CT.

PMID- 9172661
TI  - [Saving intravenously administered contrast media in CT diagnosis by using multi
      phase pumps].

PMID- 9172662
TI  - [5 years quality assurance in accordance with the roentgen regulation. Benefits,
      costs, necessary innovations].
AB  - Guidelines and standards supplementing the German "Rontgenverordnung" initiated a
      complex system of quality control in diagnostic radiology. Cost and profit are
      analysed for two hospitals of comparable size (Klinikum Buch and Klinikum
      Nurberg). The considerable expenses that must be incurred for measuring devices,
      equipment, working time and extra charges on the one hand, are the items that are
      opposed to achieving a higher image quality and dose reduction on the other.
      Public quality control enables to demonstrate the quality and to optimise imaging
      procedures in diagnostic radiology. A critical evaluation of the results of
      quality control suggests further developments. We should consider larger time
      intervals for quality tests in some cases, while focussing on techniques with
      high radiation exposure, e.g. computed tomography, where dose reductions are
      highly effective.

PMID- 9172663
TI  - [Radiology information systems: improved performance evaluation, economics and
      quality assurance?].
AB  - By means of complete service control and standardized accounting processes,
      radiological information systems clearly contribute to improved results. They
      provide the prerequisites for the establishment of expanded networks and allow
      comparisons with comparable institutions. The quality of patient care can be
      improved since, for example, the production time from referral to finished result
      becomes shorter. Direct access to patient and findings data from several
      positions is possible. Preliminary results can be viewed immediately. The
      patient's history is accessible to authorized users at all times. The exact
      reproducibility and assignment of services leads to more clarity. By means of the
      information available form RIS, rapid adaptive processes can be undertaken. The
      system assists the to fulfill the requirements of health regulations. The above
      mentioned relationships demonstrate that the EDP systems are well accepted by
      physicians, medical assistants, and administrators and represent an indispensable
      aid for solving problems.

PMID- 9172664
TI  - [Cost control without quality loss? Public Health Structure Law--requirements and
      consequences for radiology exemplified by a general hospital].

PMID- 9172665
TI  - [Diagnostic value of digital projection radiography in comparison with
      conventional roentgen technique].
AB  - Digital projection radiography provides digital data in x-ray examinations, which
      used to be carried out by examinations screen-film system combinations. The
      technological basis and clinical performances of digital luminescent radiography
      (DLR) and digital radiography are reviewed. Digital projection radiography does
      not allow to reduce selenium exposure significantly, compared to screen-film
      system combinations. Digital luminescent radiography can be used for the entire
      spectrum of analogous projection radiography the only exception being extremely
      subtile structural changes. The clinical experiences with digital selenium
      radiography achieved so far in chest x-rays are promising and the technique is
      expected to be increasing used in other anatomic regions as well.

PMID- 9172666
TI  - [AIDS-associated illnesses in radiologic diagnosis: overview and differential
      diagnosis].

PMID- 9172667
TI  - [Computerized tomography differentiation of hepatocellular carcinoma and
      cholangiocellular tumors].
AB  - 20 patients with hepatocellular carcinomas (HCC) and 18 patients with tumours of
      the biliary passages and gallbladder (CAC)) were examined via angio-CT without
      table increment and via spiral CT. Evaluation of the time-density curve of angio
      CT showed more rapid and greater enhancement in case of HCC, whereas CAC were
      characterised by slower and lesser contrast medium uptake than the surrounding
      hepatic tissue. Superior differential diagnostic information was obtained via
      angio-CT, whereas spiral CT yields the best information on extent and number of
      hepatic tumours.

PMID- 9172668
TI  - [Initial nuclear magnetic resonance tomography results of the treatment course of
      avascular femur head necrosis after femoral core decompression].
AB  - The vascular femoral head necrosis is a serious illness, especially when
      appearing in patients aged 30 to 50 years. Many etiologic factors cause a femoral
      head necrosis such as, for example, high-dose steroids, abuse of alcohol, defect
      of bone marrow and trauma of the hip. Often the X-ray photograph leads to the
      diagnosis in the second stage (ARCO 1992) or in the third stage, when the femoral
      head has begun to collapse. The stage IIc and III shows an evident enhancement in
      contrast media in MRI. Contrast enhancement is demonstrated by STIR, FATSAT, T1
      weighted and dynamic screening sequence. The characteristics of the contrast
      media enhancement argue for an active concomitant process of destruction and
      regeneration. This stage has the best chances for a drug or a surgical therapy.
      The evaluation of the signal intensity by the dynamic screening sequence is
      considered as an objective contribution for the staging of the femoral head
      necrosis. This enables one to differentiate between the curable stage IIc and the
      stage III, showing the beginning of breakdown of the femoral head.

PMID- 9172669
TI  - [Contrast media in MR mammography].
AB  - A standardized relationship between concentration of contrast media and
      normalized signal intensity should be the basis of a diagnostic evaluation of MR
      mammography at different sites and with different sequences. In this work we
      compared the dynamic range of the MR-compatible contrast medium Magnevist at
      different sequences and machines. For this purpose we made measurements with a
      phantom, consisting of MR-compatible glass tubes filled with contrast medium of
      different concentrations. The glass tubes were placed in a water bath. All
      measurements were made with breast coils. The signal intensity of the glass tubes
      was normalized to the signal intensity of the native probe (water = 1). These
      normalized dynamic curves were compared with each other in order to find, for the
      different machines, the sequence which is nearest to a defined "Standard-Curve".
      As this task proved not possible for all machines, we measured how the dynamic
      curves of the different machines related to the "Standard-Curve". For all
      sequences we made also measurements with a female student to assure the quality
      of the pictures. Thus the participating radiologists can now compare their
      dynamic measurements of breast lesions with each other.

PMID- 9172670
TI  - [Isolated tuberculosis of the liver coincident with renal cell carcinoma].
AB  - The macronodular form of hepatic tuberculosis is a very rare disease
      characterized by tumor-like tuberculomas or abscesses. Correct diagnosis is
      hampered by ambiguous clinical and radiological findings. We present a case of
      solitary tuberculosis of the liver without evidence of extrahepatic tuberculous
      manifestations. The lesions mimicked metastatic disease of a coincidentally found
      kidney tumor. Diagnosis could only be made by histologic examination of repeated
      percutaneous liver biopsies. Antituberculous treatment lead to a complete
      retrogression of hepatic changes while the kidney tumor (histologically a renal
      cell carcinoma) was removed surgically. As a liver biopsy provides the only means
      of diagnosing local nodular tuberculosis, which is treatable, we conclude that it
      should be performed on every unclear tumorous lesion of the liver.

PMID- 9172671
TI  - [Teratoma of the mediastinum--detection in conventional imaging and CT].
AB  - We report the case of a 20-years old female patient with a tumor in the anterior
      mediastinum which was coincidently detected by a conventional X-ray of the chest.
      Differential diagnose were eliminated was constructed by means of computed
      tomography showing area of fatty density. The tumor was exstirpated because of
      its possible malignancy as well as the possibility of the development of local
      complications. Histology confirmed the tentative diagnosis of fatty cystic
      teratoma.

PMID- 9172672
TI  - [Asymptomatic aneurysm of the ileocolic artery].
AB  - Visceral aneurysms are rare and account for only 5% of all abdominal aneurysms.
      Most often they cause no symptoms and are therefore incidental findings. Doppler
      ultrasonography is the diagnostic method of choice. Therapeutic procedures can be
      performed either surgically of by interventional therapeutic techniques. This
      article presents a patient case with an ileocolic artery aneurysm.

PMID- 9172673
TI  - [Assignment of a component of protein fluorescence spectra to tryptophan residues
      by their three-dimensional microoenvironmental properties].
AB  - Parameters of fluorescence of three single-tryptophan-containing proteins and of
      two log-normal components of proteinase K (2 tryptophans) were analyzed in
      relation to the microenvironment characteristics of indolic atoms in crystal
      structures of the proteins. For this purpose, it was constructed a system of
      microenvironment description including accessibility of the atoms to the bulk and
      bound water; the density, polarity and mobility of environment within radii of
      5.5 and 7.5 A from each indolic atom; and the existence of eventual partners in
      hydrogen bonding with excited fluorophore. The analysis showed that, in the cases
      of the most shorter-wavelength emission bands (those structured at 308 nm for
      azurin and at 316 nm for L-asparaginase), as well as of the monomer melittin band
      at 350 nm, the microenvironment characteristics well agreed to those predicted in
      the model of discrete states of tryptophan in proteins [1,3,7] and can be used
      for assignment of protein fluorescence spectral components to individual
      tryptophan residues. However, differences of the microenvironment parameters
      included in the system are little discernible for the component bands of
      proteinase K emission at ca. 330 and 340 nm. In order to reliably assign such
      components of tryptophan fluorescence, it seems to be sufficient to take into
      account some additional structural characteristics, which could be revealed in a
      comprehensive analysis of a great number of proteins possessing such spectral
      components.

PMID- 9172674
TI  - [Long-range electron transfer in globular proteins by polaron excitation].
AB  - Considering polaron model, we have calculated an electron state localized in the
      protein heme. Using these calculations: the electron density and electron energy,
      we estimated the self-exchange rate constant for cyt c (horse heart), its
      reorganization energy, matrix element, and dependence of this rate on the
      distance between hemes. The results are compared with the experimental data and
      other theoretical estimations. We discuss the role of polaron excitations in the
      long-range electron transfer in globular proteins.

PMID- 9172675
TI  - [Thermodynamic studies of triple-helical structures of the collagen type in
      oligotripeptides during study of molecular chain elongation].
AB  - The conformational transition collagen-like triple helix in equilibrium with
      chains of oligotripeptides Z-(Gly-Pro-Pro)n-OMe with n = 6, 7, 8 in water by
      variation of solution temperature and sample concentration has been studied using
      IR-, CD-spectroscopy and microcalorimetry methods. The straight line correlation
      between the obtained value of the transition enthalpy and entropy and the number
      of the triplets (3n - 2), involved in the interpeptide set of hydrogen bonds was
      revealed. Evidently the effect of terminal groups is really weak in this case,
      and the interpeptide bonds of the triple helix may be regarded as equivalent one
      another. The estimated cooperative block of nucleation corresponds in length to
      the one full turn of the superhelix. The state diagrams of the oligotripeptides
      with n = 6, 7, 8 in aqueous solution are presented.

PMID- 9172676
TI  - [Mechanism of magnetosensitive binding of ions by certain proteins].
AB  - For the first time a consistent physical model is proposed that explains a weak
      ELF magnetic fields effect on biological systems. The probability density changes
      are calculated in the context of an idealized quantum model for an ion within a
      protein under the magnetic field modulated on the magnitude. The dissociation
      probability of an ion-protein complex is shown to depend on the magnetic field
      parameters. It is the consequence of an interference of angular modes of an ion
      wave function.

PMID- 9172677
TI  - [ATPase and regulatory properties of skeletal muscle myosin in Citellus undulatus
      susliks during various stages of winter hibernation].
AB  - The paper is devoted to the study on enzymatic and regulatory properties of
      skeletal muscle myosin of hibernating ground squirrels (Citellus undulatus) for
      the purpose of elucidating the contribution of myosin and myosin filaments to the
      change of physiological state of the animal at the different stages of
      hibernation (hibernation, arousing, winter activity). It has been revealed that
      actin-activated ATPase activity of myosins of hibernating and arousing ground
      squirrels is less by 60 and 20%, correspondingly, than that of the myosin of
      active animals. In the absence of troponin-tropomyosin complex the Ca(2+)
      sensitivity of actomyosins of the hibernating and arousing ground squirrels is
      less by 60 and 55%, correspondingly, than that of the actomyosin of active
      animals. The results obtained by us point to the essential decrease of functional
      properties of the main contractile protein, myosin upon hibernation, which
      evidently contributes to the inhibition of moving capacity of skeletal muscles at
      this period.

PMID- 9172678
TI  - [1H-NMR study of immunoregulatory peptides].
AB  - Conformational and dynamic properties of the synthetic peptides, amino acid
      sequence of which correspond to biologically active fragments of the following
      human cytokines: alpha 2, gamma interferons and interleukins 1 beta, 2, were
      studied in aqueous solution and dimethylsulfoxide by one-dimensional and two
      dimensional 1H-NMR spectroscopy (400 MHz). The analysis of nuclear Overhauser
      effect data, values of vicinal J3(NH-C alpha H) coupling constants of amide
      protons and their temperature coefficients of chemical shifts indicate an
      unordered flexible conformation of the peptides in aqueous solutions. The
      structural and dynamic features of the peptides investigated are discussed
      together with their biological activity.

PMID- 9172679
TI  - [Fourier analysis of nucleotide sequences. Periodicity in E. coli promoter
      sequences].
AB  - Fourier spectra of E. coli promoter DNA sequences have been obtained. The
      periodical structure of individual promoter sequences is characterized. E. coli
      promoter sequences are classified according to their Fourier spectra using three
      feature sets: 1--the number of peaks in Fourier spectra; 2--values of power
      spectra for promoter primary structures and their similarity with physical
      periodicities in the backbone of polynucleotide; 3--the presence of blocks made
      of equal nucleotides. The comparison of Fourier spectra of promoter sequences and
      corresponding genes is provided. The conclusion that different ways of
      stabilization of promoter secondary structure in the case of different primary
      structure periodicities is drawn. The intermittence of AT- and GC-blocks, and
      variety of Fourier spectra mean DNA hydrate shell in DNA promoters is non
      contiguous and non-stable at junction points. Characteristic features of
      prokaryotic promoters Fourier spectra differ from human promoters.

PMID- 9172680
TI  - [Spectrophotometric study of DNA complexes with dodecyltrimethylammonium
      bromide].
AB  - Multistep nature of complex formation of bromide dodecyltrimethylammonium (DTMA)
      with thymus DNA is shown by spectrophotometric method application in the range of
      220-600 nm. While adsorbing DTMA DNA undergoes some structural changes. DTMA
      concentration raise from 0.4 to 0.8 mM per DNA provokes hydrophobic layer
      formation leading to following aggregation of the complexes. The analysis of
      light scattering in the range of 340-600 nm estimated the size of these
      aggregates. Assuming that these particles are spherical, their diameter appeared
      to be 95-110 nm.

PMID- 9172681
TI  - [Features of melting of DNA complexes with mitoxantrone at low concentrations].
AB  - The melting of DNA complexes with the anticancer mitoxantrone preparation at the
      mu = 0.11 and mu = 0.011 NaCl ionic strengths was investigated by the methods of
      microcalorimetry and spectrophotometry. It was shown, that at the 0.011 M NaCl
      the dependence of the melting temperature (Tm) upon the mitoxantrone
      concentration passed at minimum. The decrease of Tm was observed in the region,
      where one mitoxantrone molecule fell approximately on 100 base pairs DNA. There
      was observed a deeper minimum for DNA sarcoma 45. In the region of the
      mitoxantrone concentration the enthalpy of melting of the complexes increases
      linearly with the increase of the mitoxantrone concentration. The mentioned
      regularities were not observed at the mu = 0.11 M NaCl. The observed phenomenon
      is explained qualitatively by the entropy increase of the coiled state of DNA
      ligand complex on account of additional freedom of ligand's revolving.

PMID- 9172682
TI  - [Modification of the DNA spatial structure when complexed with cisplatin].
AB  - The experimental and theoretical analyses of the conformational transitions of
      DNA-cis-platinum complexes have been carried out. It is shown that at low
      concentrations of the ligand, the thermodynamic parameters of the helix-coil
      transition of the complexes are not the result of the local B-->A transition.

PMID- 9172683
TI  - [Trivaline initiates formation of homo- and heteroquadruplex DNA structures].
AB  - Formation of heterologous (calf thymus double-stranded DNA) and homologous
      (linearized pBR322 plasmid double-stranded DNA) quadruplexes upon binding with
      the simple aliphatic tripeptide derivative (dansyl hydrazide trivaline) was
      examined by fluorimetry, flow linear and circular dichroism and electron
      microscopy. The morphology of the rod-like compact particles formed due to the
      association of double-stranded DNA segments proved to be the same for both DNAs,
      whereas the stability of the compact DNA structure upon tripeptide removal from
      the complex with DNA differed substantially for homologous versus non-homologous
      double-stranded DNA used. The increase of NaCl concentration in the solution up
      to 30 mM removes the peptide from both types of the complexes completely. At the
      same time at 20 mM NaCl calf thymus DNA quadruplexes readily dissociate, whereas
      the structures formed by plasmid DNA retain their morphology in the solution
      containing NaCl with concentrations up to 40 mM and are only partially disrupted
      at even higher NaCl concentration. These results provide the analogy between
      trivaline-DNA model complexes and RecA-DNA binding.

PMID- 9172684
TI  - [Effect of hypochlorite and hydrogen peroxide on the ability of hemoglobin to
      stimulate lipid peroxidation of low density lipoproteins].
AB  - The ability of hemoglobin, modified by H2O2 or HOCl/OCl-, to induce lipid
      peroxidation (LPO) in low density lipoproteins (LDL) was studied, as well as the
      effects of haptoglobin. It was found that Hb modification by H2O2 or HOCl/OCl-
      increased generation of TBA-reactive substances in low density lipoproteins.
      Modified Hb was as double or more reactive compared to intact Hb. Free radical
      scavengers (ethanol and mannitol) gave no effect on LPO in LDL. On the other
      hand, ferric iron chelator desferrioxamine decreased LPO 5-6 times. Ferrous iron
      chelator- o-phenanthroline was effective only in the case of LPO, induced by H2O2
      modified Hb. Haptoglobin (plasma protein forming complexes with Hb) decreased LPO
      induced by both intact or HOCl/OCl modified Hb. The results of the paper show
      that modification of Hb by H2O2 or HOCl/OCl- increase the ability of Hb to induce
      LPO in LDL, probably due to metHb, ferrylHb or free iron production.

PMID- 9172685
TI  - [Effect of ischemic damage factors on lipid peroxidation in rat brain
      synaptosomes].
AB  - Accumulation of TBA-reactive substances after a 40 min incubation of rat brain
      synaptosomes at 37 degrees C was analysed. A lowering of pH to 6.5-5.5 or
      arachidonic acid (0.1-1.0 mM) increased lipid peroxidation which was blocked by
      antioxidants. Acidosis (pH 6.0) and arachidonic acid used in combination had a
      strong synergic effect. Depolarisation of plasma membranes or intrasynaptosomal
      mitochondria were without influence on lipid peroxidation at neutral or acid pH.
      The results support a leading role of acidosis and phospholipases in stimulation
      of peroxidation under ischaemia.

PMID- 9172686
TI  - [Effect of acidosis on membrane potential and calcium transport in rat brain
      synaptosomes].
AB  - The influence of acidosis on the transmembrane potential, sodium pump and
      membranous systems of calcium transport was studied on isolated presynaptic nerve
      terminals (synaptosomes) from rat brain. It is established that acidic shift
      causes a decrease of membrane potential, a large inhibition of the sodium pump
      (by three times at pH 6.0). All the systems controlling both inward- and outward
      directed calcium fluxes are partially blocked by low pH. At pH 6.0 the basal
      influx and calcium pump are reduced two-fold while the voltage-sensitive calcium
      channels and Na+/Ca2+ exchanger are inhibited by three and four to five times,
      respectively. We have no found any evidence of acidosis-induced net flux of
      calcium directed inwards.

PMID- 9172687
TI  - [The theory of biomembrane elasticity].
AB  - The dielectric permeability of the different layers of biological membrane were
      investigated. The objects taken into account included a lipid bilayer, membrane
      proteins and external covers formed by clumps of protein chains. The distribution
      of electric fields and the values of electrostatic forces of membrane elastic
      layers stretching was found in such membrane.

PMID- 9172688
TI  - [Prospects for studying biomembrane elasticity fluctuations].
AB  - The fluctuations of membrane elasticity accompanying the substratum binding and
      dissociation with the macromolecules incorporated into the bilayer can bear some
      information on constants of binding reactions as well as on the size of
      distortion zones around incorporated macromolecules as well as on their number in
      the membrane. The measurement of membrane elasticity fluctuations can be also
      used for the biosensors containing supported bilayers.

PMID- 9172689
TI  - [The role of nonspecific troponin in kinetics of intracellular calcium in
      cardiomyocytes].
AB  - According to literature data nonspecific troponin TnC2 binds calcium in cardiac
      myocytes slowly and does not influence calcium transient. Therefore TnC2 often
      was not taken into consideration in models of the intracellular calcium kinetics.
      The mathematical model of the intracellular Ca(2+)-binding system we developed
      includes TnC2 as a ligand. Rate constants accepted for the complexation of Ca2+
      by intracellular ligands give good agreement of the theoretical data with
      observed physiological ones. We compared the results of numerical experiments on
      this model with similar results obtained on the other model where TnC2 had been
      ignored. Some essential differences were revealed. In the model without TnC2 the
      fraction of calcium binding to specific troponin TnC1 always is smaller than the
      fraction of Ca2+ bound to the other ligands together. In our model TnC1 fraction
      (it regulates the mechanical response of muscle) is bigger that means more
      effective Ca(2+)-binding during activation of contractile proteins. The results
      above show that within the frame of our model the constants taken for Ca(2+)
      binding ligands are more substantiate.

PMID- 9172690
TI  - [Digitonin-sensitive calcium pool and its change during synchronous division of
      Tetrahymena pyriformis cells].
AB  - A very significant intracellular pool of calcium, sensitive to digitonin action
      and different from one of free cytozolic Ca2+, has been shown to exist in the
      cells of ciliate protozoan T. pyriformis. Calcium content in digitonin-sensitive
      pool NdigCa2+ has been estimated throughout the cell cycle in synchronized
      culture of T. pyriformis. The value of NdigCa2+ decreased in the period of time
      prior to and at the cell division, whereas after the division itself it
      increased. The possible role of the calcium content changes of digitonin
      sensitive pool in regulation of cytozolic Ca2+ level and in control of cell
      division is discussed.

PMID- 9172691
TI  - [Increase in access to SH-groups of membrane proteins in Ehrlich ascites
      carcinoma cells upon purinergic receptor activation].
AB  - The effect of ATP on SH-groups accessibility of the surface membrane proteins in
      Ehrlich ascites tumor cells has been studied using a fluorescent nonpenetrating
      reagent Thiolyte MQ. No accessible protein SH-groups in plasma membrane of
      unstimulated cells have been found. The accessibility of SH-groups in proteins
      with molecular masses 82 and 23 kDa was increased in 10 s after the ATP addition.
      The data are interpreted as a result of the conformational transition or vertical
      translocation of certain thiol-bearing membrane proteins at purinoreceptor
      activation. The effect may apparently be coupled to the changes in the membrane
      potential and calcium concentration in the cytoplasm occurring in the same time
      interval.

PMID- 9172692
TI  - [Effect of an antioxidant (ubiquinone Q-9) and chronic low-dose irradiation on
      rat chromatin structure and T-lymphocyte proliferation].
AB  - We have demonstrated the protective effect of natural antioxidant coenzyme Q-9 on
      the T-cell proliferative capacity and chromosomal DNA state under low dose
      chronic irradiation. The DNA-staining fluorescent dye Hoechst-33258 and acridine
      orange were to observed the nuclear morphology changes in T-lymphocytes.
      Ubiquinone diet partially restored the decreasing in immune response and the
      luminescence intensity of DNA-Hoechst-33258 complex in T-cells of low dose
      irradiated rats.

PMID- 9172693
TI  - [Photosensitizing properties and antioxidant activity of furagin--an
      antimicrobial drug that is a derivative of nitrofuran].
AB  - Photosensitizing effect of antimicrobial drug nitrofuran derivative--furagin N-(5
      nitro-2-furil)-allylidencamino-hydantoin) under irradiation with light longer
      than 280 nm was found. The method of investigation is based on
      photochemiluminescence of Gly-Trp peptide in aqueous solution. Maximum
      photosensitizing efficiency was observed at the furagin concentration 0.08 mM
      when chemiluminescence yield was 33 times greater than photochemiluminescence of
      Gly-Trp peptide in absence of drug. It was shown that photochemiluminescence
      sensitized by furagin occurred via free radical way. Life time of the triplet
      state of furagin determined by flash photolysis was 40 microseconds. A comparison
      of experimental data with kinetic calculation allowed us to estimate the rate
      constant of triplet quenching by oxygen ((2.2 +/- 0.3)10(8) M-1.s-1) and the
      total rate constants of physical quenching and chemical reaction with Gly-Trp
      peptide ((2.0 +/- 0.4)10(8) M-1.s-1). It was also found in experiments with
      photochemiluminescence of Gly-Trp peptide sensitized by riboflavin (irradiation
      with monochromatic light 436 nm) that furagin possesses antioxidant properties
      twice reducing the intensity of chemiluminescence at the drug concentration 0.029
      mM.

PMID- 9172694
TI  - [Antioxidant properties of a series of extracts from medicinal plants].
AB  - Investigation of antioxidant properties of some plants was carried out. A group
      of plants affected human central nervous system was studied in detail. Efficiency
      of plants as antioxidants was tested by the influence of their extracts on the
      yield of photochemiluminescence of Gly-Trp solutions. Antioxidant properties were
      examined under conditions when their own absorption was minimized. Riboflavin as
      additional sensitizer was used in this experiment for superoxide generation. The
      antioxidant effect was evaluated with regard to single dose of plant extracts and
      their concentration in human organism. The effect decreases in the following
      consequence: Hypericum > Eleutherococcus > Rhodiola > Leonurus > Aralia >
      Valeriana > Echinopanax > Schizandra > Panax gin-seng.

PMID- 9172695
TI  - [Inhibition of cytochrome P-450 when exposed to nitro-compounds].
AB  - Changes in ESR signals from the active form of cyt P-450 in mouse liver samples
      after administration of some nitro compounds were studied by the ESR method. It
      is shown that administration of nitro compounds leads to the formation of
      nitrosyl cyt P-450-NO complexes and a decrease in the ESR signal from cyt P-450
      within the first 1-2 h after administration, indicating the inhibition of enzyme
      activity. It is assumed the nitro compounds induced inhibition of cyt P-450 in
      the first hours after administration is responsible for the enhancement by
      imidazoles of the effect of some chemotherapeutic drugs.

PMID- 9172696
TI  - [Hydrophobic and hydrophilic complexes of Fe2+ with dithiocarbamate derivatives
      as a nitric oxide trap in mice].
AB  - It has been shown by using EPR method that hydrophobic complexes Fe(2+)
      diethyldithiocarbamate (DETC) act more efficiently as a selective traps of nitric
      oxide (NO) in mice organisms than hydrophilic complexes Fe(2+)-N-methyl-D
      glutamyldithiocarbamate (MGD). This difference seemed to be due to higher
      stability of paramagnetic mononitrosyl iron complexes with DETC (MNIC-DETC)
      formed in vivo in animal tissues in a result of NO binding with Fe(2+)-DETC
      complexes. Analogous complexes MNIC-MGD appeared a blood were oxidized to
      diamagnetic, EPR silent form. The latter was also detected in mouse urine
      especially for animals which were pretreated with bacterial lipopolysaccharide
      inducing increased NO generation in mice organisms. Nitrogen dioxide or
      peroxynitrite formed endogenous NO were suggested to be the agents which oxidized
      MNIC-MGD by reversible way in mice organisms.

PMID- 9172697
TI  - [A system for computer visualization of excitation wave propagation in the
      myocardium].
AB  - A method of computer-aided visualization of autowave vortices on the cardiac
      tissue surface is developed. The software for research into autowave vortex
      evolution is designed, which allowed an adequate presentation of excitation
      propagation along complex trajectories and the detection of the most essential
      features of excitation source behavior.

PMID- 9172698
TI  - [The defining role of calcium entering cells during ischemia as the mechanism for
      initiating reperfusion arrhythmias].
AB  - The role of calcium ions entering cells upon both reperfusion and previous
      ischemia for reperfusion arrhythmias has been studied on the experimental model
      of isolated rat right ventricle perfused through coronary artery. Manipulation by
      concentration of calcium ions in both perfusion and reperfusion solutions
      demonstrates that calcium ions entering cells during ischemia but not upon
      reperfusion play a dominant role in the initiation of reperfusion tachysystoles
      (RTS) and reperfusion extrasystoles. It is shown that mechanisms of reperfusion
      fibrillations (RF) are more sensitive than ones of RTS to changes of the
      intracellular calcium concentration. For example, RF have been easily suppressed
      by calcium concentration decreasing at any stage of the experiment: upon
      reperfusion, or during previous ischemia, whereas RTS have not been suppressed
      even under total removal of calcium from solutions either before initiation of
      ischemia or during following reperfusion. Multielectrode mapping revealed focal
      sources arising as the mechanism underlying not only reperfusion arrhythmias as
      it has been shown before [4.7] but also arrhythmias that have been observed
      through experiments.

PMID- 9172699
TI  - [Assessment of the contribution of complex and simple Purkinje cell impulses to
      local potentials of the cerebellar cortex].
AB  - Potentials amplitude decrement with the distance between referent cell and test
      electrode is estimated by means of potential averaging synchronous with complex
      and simple spikes of the referent Purkinje cell. Anisotropy of recorded fields in
      accordance with natural planes of anisotropy of cerebellar cortex and temporal
      parameters of complex and simple spikes has been described. Use of synchronous
      averaging for increase of a probability of finding of Purkinje cells pairs
      controlled with the same climbing fiber is discussed.

PMID- 9172700
TI  - [Phenomenological theory of the recuperative period of the living organism].
AB  - A phenomenological nonlinear model, describing a reconstruction of the living
      organism after strong loading have been proposed. This model is describing a
      restitution dynamics of the organism functional state to the initial state,
      including a supercompensation stage. In a simplest (one-component) case this
      model is overdamping Duffing oscillator. It is shown that the mutation phenomena
      may be described as the phase transition within the framework of Landau
      Khalatnikov approach. A generalized many-component nonlinear reconstruction model
      is proposed.

PMID- 9172701
TI  - [Comparative study of three antineoplastic alkylating agents on DNA].
AB  - The influence of three alkylating anticancer preparations phosphamide,
      sarcolysine, cyclophosphane on content of the 5-methylcytosine and parameters of
      the melting DNA of the liver healthy animals and tumor sarcoma 45 was
      investigated. It was shown, that among the investigated preparations
      cyclophosphane has stronger anticancer influence and comparatively weaker side
      effect on DNA liver. We came to the conclusion that it is preferable to use this
      preparation.

PMID- 9172702
TI  - Psychiatry needs a basic science titled sociophysiology.

PMID- 9172703
TI  - Serum triiodothyronine elevation with posttraumatic stress disorder: a cross
      cultural study.
AB  - This study examines the thyroid hormonal profile in Israeli combat veterans with
      posttraumatic stress disorder (PTSD) and compares it with the previously reported
      profile in American Vietnam combat veterans with PTSD. Eleven male combat
      veterans with PTSD were compared with 11 normal subjects. Thyroid junction was
      evaluated by the measurement of serum total triiodothyronine (TT3), free
      triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), thyroxine
      binding globulin (TBG), and thyroid-stimulating hormone (TSH). The mean total T3
      level in the Israeli PTSD patients (160.5 ng/dL) was significantly elevated (t =
      2.53, p < .02) above that of the comparison group (135.5 ng/dL). Total T3 mean
      levels were not significantly different between the Israeli PTSD group and two
      American PTSD groups, but all three PTSD groups had significantly higher total T3
      levels than both Israeli and American comparison groups. This preliminary study
      indicates that T3 elevation in combat-related PTSD may extend across cultures and
      suggests that further comparison of Israeli and American PTSD and normal groups
      may be useful in evaluating the significance and implications of the unusual
      alterations in the thyroid system in PTSD.

PMID- 9172704
TI  - Positive symptoms of psychosis in posttraumatic stress disorder.
AB  - The possible presence of hallucinations and delusional thoughts in posttraumatic
      stress disorder (PTSD) was investigated. Other symptom clusters were also
      assessed in order to further clarify the nature of PTSD. Twenty combat veterans
      with PTSD were compared to 18 combat veterans without PTSD on symptom rating
      scales. The subjects with PTSD exhibited a greater degree of depression, anxiety,
      agitation, anhedonia, and positive symptoms of psychosis than the comparison
      group. Specifically, the PTSD group manifested increased hallucinations,
      delusions, and bizarre behavior. Some of these positive symptoms did not appear
      to be due to reexperiencing of the trauma. The groups were not significantly
      different on indices of mania, thought disorder, or inertia. The clinical and
      diagnostic implications of the results are discussed. A diagnosis of PTSD should
      be considered with patients who have positive symptoms in the absence of thought
      disorder.

PMID- 9172705
TI  - Enlarged frontal P300 to stimulus change in panic disorder.
AB  - This study investigated event-related potential (ERP) indices of information
      processing in sufferers of panic disorder (PD). ERPs were recorded from 14 PD
      patients and 15 controls during an auditory target detection task. The task
      required subjects to discriminate infrequent target tones (p = .14; 2000 Hz) from
      frequent (p = .72; 1000 Hz) and infrequent (p = .14; 500 Hz) distractor tones. A
      frontal P300 (P3a) identified in the PD group was characteristic of activity that
      would be expected to novel, task-irrelevant stimuli and is consistent with
      junctional pathology involving the prefrontal-limbic pathways. This study
      provides psychophysiological evidence of an abnormality in PD of the brain's
      processing of physical changes in the stimulus field that occurs even under
      conditions of low stimulus load. It may assist in helping to understand the
      breakdown in information processing that occurs in PD under high load conditions
      such as crowds and supermarkets.

PMID- 9172706
TI  - Serum prolactin, growth hormone, total corticoids, thyroid hormones and
      thyrotropine during serial therapeutic sleep deprivation.
AB  - In 13 patients fulfilling DSM-III-R criteria for a major depressive episode,
      hormone serum levels were measured at 8 AM on the day before and on the first and
      second days after partial sleep deprivation (PSD) late in the night during a 4
      week course of therapy with amitriptyline in combination with 6 PSDs. Prolactin,
      human growth hormone (HGH) and total corticoids were not influenced by PSD. In
      contrast, T3 and thyrotropine (TSH) were elevated significantly on the 1st day
      after PSD throughout the series, but T4 less regularly. Although TSH reverted
      regularly to baseline values on the 2nd day after PSD, i.e. after a full night's
      sleep, T3 remained elevated. The hormones under discussion do not predict the
      therapeutic PSD effect. Nor can any correlation be determined between endocrine
      and clinical changes on the 1st or 2nd day after PSD. In connection with findings
      from sleep deprivation research in animals and in healthy subjects, the results
      suggest that thyroid changes under PSD may be nonspecific and unrelated to
      antidepressive PSD effects.

PMID- 9172707
TI  - Effects of bright light on sleepiness, melatonin, and 25-hydroxyvitamin D(3) in
      winter seasonal affective disorder.
AB  - Sixteen patients with winter seasonal affective disorder and 13 healthy controls
      were exposed to 3300 lx of cool-white fluorescent light for either 1 hour or 15
      min in the morning for 2 weeks during the winter. Subjective sleepiness,
      melatonin concentration in saliva, and serum 25-hydroxyvitamin D(3) concentration
      were measured before and after the 2-week trial as well as the following summer
      when the patients were well. There were no significant differences in the
      baseline values between the patients and healthy subjects. No significant
      differences in the outcome measures were observed in the patients or the controls
      in the two groups of each after the trial. The exposure to bright light resulted
      in a significant decrease in subjective sleepiness early in the evening in the
      patients but not in the control subjects. The reduction of depressive symptoms
      was associated with the decrease in subjective sleepiness but not with the
      changes in the melatonin or vitamin D concentrations.

PMID- 9172708
TI  - ERP changes in alcoholics with and without alcohol psychosis.
AB  - The present study compared alterations of event-related brain potentials (ERPs)
      in subgroups of chronic alcoholics with different complications during alcohol
      withdrawal. Twenty alcoholics with only mild to moderate alcohol withdrawal
      symptoms, two groups of alcoholics with histories of either delirium tremens (n =
      9) or alcohol hallucinosis (n = 13), and a control group of 38 nonalcoholics were
      examined. Patients were tested in unmedicated state and not earlier than 14 days
      after drinking cessation. An auditory Oddball paradigm and a visual Letter
      Matching paradigm were used as cognitive tasks. In the auditory task, all
      alcoholic groups exhibited delayed N200 and P300 latencies and a reduced P300
      amplitude as compared to nonalcoholics. In the visual task, only P300 amplitude
      was significantly diminished. Patients having suffered from delirium tremens or
      alcohol hallucinosis showed greater Oddball P300 amplitudes than alcoholics with
      uncomplicated withdrawal syndrome. Furthermore, delirium and hallucinosis
      patients differed in their ERPs, with hallucinosis patients showing an earlier
      P300 peak in both the auditory Oddball and the Letter Matching task. It is
      concluded that changes in ERPs during abstinence might reflect specific
      neurophysiological dysfunctions in alcoholics prone to different alcohol-related
      psychoses.

PMID- 9172709
TI  - Antagonism by benzodiazepines of the effects of serotonin-, but not
      norepinephrine-, uptake blockers in the learned helplessness paradigm in rats.
AB  - Benzodiazepines are routinely administered in combination with antidepressant
      drugs. Such combination can induce pharmacodynamic or pharmacokinetic
      interactions resulting in either a potentiation or a reduction of the effects of
      one of the drugs. The present study was undertaken to determine the effects of
      benzodiazepines alone and in combination with two classes of antidepressant
      drugs: "specific" norepinephrine uptake blockers (desipramine, maprotiline) and
      specific serotonin uptake blockers (indalpine, fluvoxamine) in the learned
      helplessness paradigm in rats. The present results show that daily injection of
      diazepam (0.2-2 mg/kg) and lorazepam (0.06-0.25 mg/kg) did not reverse the
      helpless behavior. The reversal of helpless behavior induced by indalpine (1
      mg/kg/day) or fluvoxamine (4 mg/kg/day) was antagonized dose-dependently by daily
      coadministration of benzodiazepines. In contrast, the effects of desipramine (24
      mg/kg/day) or maprotiline (48 mg/kg/day) were not modified.

PMID- 9172710
TI  - HLA antigens in schizophrenia and mood disorders.
AB  - The frequencies of HLA antigens were examined in a sample of 75 patients with
      schizophrenia and 35 patients with mood disorders. We compared the data obtained
      from this population with data obtained in another study with 3731 healthy
      subjects. Statistically significant increases were observed in the frequencies of
      HLA A10, A11, and A29 and a statistically significant decrease was observed in
      the frequency of HLA A2 in patients with schizophrenia. The increased frequency
      in HLA B16 in patients with mood disorders was also statistically significant.

PMID- 9172711
TI  - Special issue. Mental resources: intensive and selective aspects. Papers
      presented at the workshop on psychophysiology of mental resources. Amsterdam, the
      Netherlands, September 5-8, 1995.

PMID- 9172712
TI  - [Effectiveness of anesthetic gas scavengers fulfilling EN 740 requirements with
      reference to equipment leakage and fresh gas flow].
AB  - PURPOSE: During inhalation anaesthesia, contaminations of the working environment
      be anaesthetic volatiles and nitrous oxide occur. The amount of leaking gases is
      influenced by leakages of the anaesthetic ventilator, by fresh-gas flows and by
      the effectivity of the scavenging system. Since 1st January 1996 new ventilators
      have to be equipped with scavenging devices according to the European standard EN
      740. We measured the effectivity of this system with anaesthetic ventilators of a
      type that is now superseded (mean leakage rate 100 ml/min) and recent devices
      (mean leakage rate 5 ml/min) using high and low fresh-gas flows. MATERIAL AND
      METHODS: The anaesthetic ventilators were placed in a non-air-conditioned area. A
      test lung was ventilated with gas flows of 1 l/min, 3 l/min and 6 l/min
      (concentrations of nitrous oxide 70%, Enflurane 1%). The ventilation time in each
      case was 1 h. The minute volume was set to 8 l/min. At 2-minute intervals the
      concentrations of nitrous oxide and enflurane were measured by a multigas monitor
      Bruel & Kjaer 1302. The experiments were carried out with an old scavenging
      device according to DIN 13260 and a new device according to EN 740. RESULTS:
      Using the scavenging device according to DIN 13260, the concentrations of the
      pollutant gases were significantly dependent on the fresh-gas flows. No
      differences were found when using old or new anaesthetic ventilators. Medians of
      nitrous oxide (n2o) and Enflurane (e): 6 l/min: (n2o) 204 ppm (e) 4.3 ppm 3
      l/min: (n2o) 115 ppm (e) 2.1 ppm 1 l/min: (n2o) 61 ppm (e) 0.97 ppm. Scavenging
      devices according to EN 740 significantly reduced the amount of emitted
      pollutants. No dependency on fresh-gas flows could be detected. 6 l/min: (n2o)
      11.25 ppm (e) 0.05 ppm 3 l/min: (n2o) 10.12 ppm (e) 0.0 ppm 1 l/min: (n2o) 9.5
      ppm (e) 0.0 ppm. CONCLUSIONS: The formerly reported dependence of the room air
      concentrations of anaesthetic volatiles and nitrous oxide from the fresh gas flow
      are caused by the spillage of pollutants through scavenging devices according to
      DIN 13260. The use of systems according to EN 740 is not only useful in new
      devices but must also be recommended for superseded models of anaesthetic
      ventilators.

PMID- 9172713
TI  - [Post-traumatic cerebrospinal rhinorrhea].
AB  - PURPOSE: Since frontobasal fractures after severe head trauma may cause serious
      late-term complications such as meningitis, their recognition and operative
      treatment are essential. Therefore, we analysed the importance of
      rhinoliquorrhoea as an early symptom of such fractures by comparison with
      neuroradiological methods. MATERIAL AND METHODS: In all patients undergoing
      operative revision of frontobasal fractures during a 7-year period, the clinical
      symptoms, results of neuroradiological examinations, concomitant injuries, as
      well as operative results, were studied retrospectively. RESULTS: 45 patients out
      of 688 with severe head injury showed frontobasal fractures (6.5%). The most
      common cause of these injuries were traffic accidents (55%) and precipitated
      falls or plunges (35%). Posttraumatic rhinoliquorrhoea was seen in 41 of 45
      patients (91%), and 30 showed external periorbital injuries (66%). In 8 patients
      (18%) the frontobasal fractures could not be visualised by facultatively
      performed neuroradiological methods (coronary CT-scan, CT-cisternography,
      subarachnoid space scintigraphy). 15 patients (33%) were secondarily transferred
      to our institution, two of them more than two years after the causative injury.
      All patients were operated on successfully within 14 days after admission.
      CONCLUSION: Traffic accidents and precipitated falls or plunges are the main
      causes of head injuries with frontobasal fractures and about 2/3 of these
      patients show external periorbital injuries. Rhinoliquorrhoea as an early symptom
      allows diagnosis of frontobasal fractures in 90% of all cases rather than
      neuroradiological methods which failed to demonstrate frontobasal fractures in
      about 20% of our patients. Therefore, recognition of rhinoliquorrhoea in patients
      with severe head injury is essential.

PMID- 9172714
TI  - [Diagnosis of pleural effusion in intensive care patients with supine digital
      thoracic imaging. A study of CT validated cases].
AB  - PURPOSE: The significance of the recumbent chest x-ray using digital luminescence
      radiography was to be assessed in respect of diagnosis of pleural effusions.
      MATERIAL AND METHODS: Three experienced radiologists evaluated 32 digital
      recumbent chest x-rays of 32 intensive-care patients. The radiologists were asked
      to estimate the effusion volume and to assess whether typical x-ray signs of
      pleural effusions were seen. These evaluations were compared with one another and
      with the simultaneously produced CTs. RESULTS: Diagnostic accuracy of the digital
      recumbent chest x-ray is of medium quality in respect of diagnosis of pleural
      effusions (sensitivity: 69%, specificity: 54%, positive predictive value: 81%,
      negative predictive value: 34%, rate of accuracy: 65%). Diagnostic safety is the
      same for right-sided or left-sided pleural effusions, and increases with
      increasing effusion volume. The ratings by the radiologists are statistically not
      significantly different, but are significantly different from the CT measurements
      (Wilcoxon test, p < 0.05). Correlations of the assessments and the measurements
      were weakly positive (r = 0.24, r = 0.36, r = 0.47). The pleural effusions were
      on the average underestimated by the radiologists. The median predictive error
      was 203 ml. CONCLUSIONS: Recumbent chest x-ray with digital luminescence
      radiography is an imaging method of limited accuracy in respect of diagnosis of
      pleural effusions. Supplementary diagnostic methods are recommended, as the
      present results show, especially in such cases where the recumbent chest x-ray
      does not reveal an effusion or if the volume must be determined accurately.
      Digital recumbent chest x-ray ranks equal with conventional x-ray in the
      diagnosis of pleural effusions.

PMID- 9172715
TI  - [Routine bacteriological screening of intensive care patients: contra].

PMID- 9172716
TI  - [Routine bacteriologic screening of intensive care patients: pro].

PMID- 9172717
TI  - [Postoperative therapy of an alcoholic patient with an unusually high ethanol
      metabolic rate].
AB  - To avoid alcohol withdrawal syndrome (AWS) a pre-operative withdrawal, post
      operative drug therapy or continued substitution of ethanol may be tried.
      However, substitution of ethanol needs an exact dosage and has to be controlled
      very carefully. The dose calculation is based on an assumed breakdown rate of
      0.15 g%/1000/h, as evaluated in forensic studies. We report on a patient who
      throws the basis for these calculations into question. The breakdown rate of this
      43-year-old man was extraordinary higher than the average turnover. This high
      level of the turnover rate occurred with no detectable impairment of the liver or
      other organs. This case demonstrates the importance of a close control of the
      blood alcohol level during the post-operative administration of ethanol. The
      individual doses of ethanol to avoid AWS has to be found individually for each
      patient.

PMID- 9172718
TI  - [Angioedema of the mucous membranes of the upper aerodigestive tract after
      administration of ACE inhibitors].
AB  - Inhibitors of angiotensin converting enzyme may rarely cause an angioneurotic
      oedema of the upper aerodigestive tract. The pathomechanism of this side effect
      depends on an interaction of the drug with hormones regulating the vascular
      resistance such as the kallikrein kinin system and the prostaglandin system.
      Anglo-oedema is characterised by subcutaneous or submucosal swelling, which
      preferably affects the lips, the soft palate, the tongue and the larynx.
      Pathomechanisms, differential diagnosis and treatment of ACE-inhibitor induced
      oedema of the upper aerodigestive tract are described by means of 3 case reports.

PMID- 9172719
TI  - [Bacillus cereus pneumonia after thoracic trauma. Case report and review of the
      literature].
AB  - We report on the case of a pneumonia caused by Bacillus cereus in a patient who
      sustained severe thoracic trauma, fractures of ribs 3-12, left lung contusion and
      haematopneumothorax. Bronchoscopic alveolar lavage (BAL) performed on ICU day
      four helped identifying the underlying cause of pneumonia. Inspite of early
      diagnosis and antibiotic treatment with clindamycin, cefotaxim and tobramycin,
      which rapidly eliminated the bacteria from the patient's lungs, the patient
      eventually died from the severe underlying injuries. However, this case
      emphasises that early performed BAL and rapid microbiological staining techniques
      can help diagnose pneumonia in critically ill patients. We also review the
      literature on pulmonary infections caused by Bacillus cereus.

PMID- 9172720
TI  - [Peculiarities of endotracheal intubation in the child].

PMID- 9172721
TI  - [Management of frontobasal fractures: an interdisciplinary challenge].

PMID- 9172722
TI  - [Positioning trauma in anesthesia and surgical intensive care medicine (2)].
AB  - Specific modes of positioning are essential for successful surgery. These are
      again critically assessed in this final part of our review. Technically correct
      execution can minimize the risk of damage caused by positioning, although the
      possibility of damage still exists. First of all, the position on the fracture
      table is discussed. Great care must be taken concerning the perineal post and leg
      holder. In the lateral decubitus position, the correct positioning of head and
      spine as well as that of the lower arm are of great importance. When using the
      Trendelenburg and reverse Trendelenburg position, the effect on the
      cardiopulmonary system and the intracranial pressure must to be taken into
      consideration. Prone position and its modifications (i.e. tuck position) demand
      diligent care concerning the positioning of the head. There must be absolutely no
      bulbus compression and the abdominal wall should not be under pressure. While
      employing the sitting position, the patient should be adequately monitored so
      that venous air embolism can be recognized and treated as soon as possible.
      Because of the increased occurrence of grave complications, the sitting position
      should be used only if this is absolutely necessary.

PMID- 9172723
TI  - [The AIDS patient in anesthesia].
AB  - Treatment of a patient with Acquired Immune Deficiency Syndrome (AIDS) is very
      challenging, and makes great demands on the anaesthesiologist. Any of an AIDS
      patient's vital organ systems may be compromised, either by the human
      immunodeficiency virus (HIV) itself, opportunistic infections, by tumours, or as
      a result of AIDS-related drug therapies. Infections of the lungs (e.g.,
      Pneumocystis carinii pneumonia) are prevalent, and cardiac impairment can be
      found in as many as 50% of AIDS patients. In addition, disorders of the central
      and peripheral nervous system and water and electrolyte imbalances are often
      seen. Perioperatively, the AIDS patient is especially prone to infections as a
      result of a compromised immune system. The choice of anaesthetic procedure for
      the AIDS patient-aside from the type of operation-depends on the severity of the
      illness and progression of organ impairment. All anaesthesia personnel must be
      careful to avoid infection, as they frequently come in contact with the blood or
      body fluids of their patients. However, the risk of being infected by an AIDS
      patient is very low, provided hygiene regulations are followed strictly. The rate
      of seroconversion after accidental needle-stick injury is below 1%. If exposure
      does occur, regular serologic controls should be continued for one year.
      Prophylactic treatment with azidothymidine after exposition to HIV is
      recommended.

PMID- 9172724
TI  - [Effect of lidocaine administration mode on decreasing injection pain caused by
      propofol].
AB  - Pain is a well known complication of propofol injection. Many methods are
      described to reduce it but often empirical ways are used. In this study we
      attempt to determine the effects of premixing propofol with lidocaine or to
      preinjecting lidocaine in a hand vein in combination with using a tourniquet
      before we applicated propofol. Our study shows that both ways are able to reduce
      the injection pain but premixing with lidocaine 0.05% is less effective than
      giving a bolus of lidocaine before the propofol injection.

PMID- 9172725
TI  - [Burst suppression detection in pEEG].
AB  - In the present paper, experience with the detection of burst suppression in the
      pEEG is described. The possibilities and limitations of the method during
      monitoring of anaesthesia under real conditions are discussed.

PMID- 9172726
TI  - [Model based study of myocardial stimulation mechanisms].
AB  - The present study investigated the mechanisms of electrical stimulation of a
      myocardial fibre with the aim of developing improved minimally invasive
      stimulation methods. Using a dynamic myocyte model, the ionic currents crossing
      the voltage-dependent channels of the membrane are computed. To trigger an action
      potential, the membrane must first be depolarized to the threshold potential,
      when further depolarization continues spontaneously through the avalanche-like
      opening of the sodium channels. For the development of an action potential, not
      merely the amount of charge injected into the cell during the stimulus is of
      importance, but an above-threshold magnitude of the stimulation current is also
      required. The smallest energy required is achieved when the stimulus duration is
      chosen to be equal to the chronaxie. A second aspect of the study concerned the
      far-field stimulation of a muscle fibre, achieved by generating a potential
      gradient along the fibre. First, using a continuous fibre model, the fibre
      activating function is computed. In a more detailed study, the discrete segmental
      structure of the fibre determined by the gap junctions is taken into account, and
      the impact of these junctions on the activating function analysed. By optimizing
      the electrode configuration, an appropriate activating function results which
      guarantees successful stimulation when its maximum is above than threshold
      potential. The most important finding is that the myocardium can be stimulated by
      floating electrodes, thus opening up new possibilities for a less invasive
      electro-stimulation of the heart.

PMID- 9172727
TI  - [Epiduroscopy with access via the sacral canal. Some constructional equipment
      requirements from the anatomic and biomechanical viewpoint].
AB  - To ensure optimal mechanical functioning of the vertebral column, intact symmetry
      of its bony and muscular elements is mandatory. With this in mind, the need to
      reduce the invasiveness of spinal surgery is even greater than that applying to
      surgery in general. To avoid bony or muscular damage during surgery, in
      particular in the case of the segments L4/L5 and L5/S1-which are particularly
      prone to intervertebral disc rupture-laser discotomy procedures, with
      introduction of instruments via the sacral canal during epiduroscopy are
      presently being developed. Preliminary experiments on human corpses have
      demonstrated the practicability of the technique, but specially designed
      instruments have yet to be developed for use in patients. In an attempt to define
      the conditions of important for the design of the instrument, we have carried out
      a morphometric analysis of 100 sacral bones (56 females; 44 males). The
      configuration of the sacral canal is described in quantitative terms, and the
      results used to determine the diameters and curvatures of the instruments needed
      for laser discotomy.

PMID- 9172728
TI  - [Asymptotic behavior of calculated concentration time curves].
AB  - The measured concentration time curve of an injected substance is often used as a
      basis for calculating the distribution volume. For the first time, the present
      paper describes a generally applicable formula for calculating the asymptote of a
      concentration time curve in medical applications. With a knowledge of this
      formula, previously unexplained phenomena (varying results obtained from two
      different methods of calculating the distribution volume) can now be understood.
      At the same time, errors of methodology (choice of injection and measuring sites)
      can be avoided.

PMID- 9172729
TI  - Structure and dynamics of hydronium in the ion channel gramicidin A.
AB  - The effects of the hydronium ion, H(3)0+, on the structure of the ion channel
      gramicidin A and the hydrogen-bonded network of waters within the channel were
      studied to help elucidate a possible mechanism for proton transport through the
      channel. Several classical molecular dynamics studies were carried out with the
      hydronium in either the center of a gramicidin monomer or in the dimer junction.
      Structural reorganization of the channel backbone was observed for different
      hydronium positions, which were most apparent when the hydronium was within the
      monomer. In both cases the average O-O distance between the hydronium ion and its
      nearest neighbor water molecule was found to be approximately 2.55 A, indicating
      a rather strong hydrogen bond. Importantly, a subsequent break in the hydrogen
      bonded network between the nearest neighbor and the next-nearest
      neighbor(approximately 2.7 -3.0 A) was repeatedly observed. Moreover, the
      carbonyl groups of gramicidin A were found to interact with the charge on the
      hydronium ion, helping in its stabilization. These facts may have significant
      implications for the proton hopping mechanism. The presence of the hydronium ion
      in the channel also inhibits to some degree the reorientational motions of the
      channel water molecules.

PMID- 9172730
TI  - Covalent immobilization of native biomolecules onto Au(111) via N
      hydroxysuccinimide ester functionalized self-assembled monolayers for scanning
      probe microscopy.
AB  - We have worked out a procedure for covalent binding of native biomacromolecules
      on flat gold surfaces for scanning probe microscopy in aqueous buffer solutions
      and for other nanotechnological applications, such as the direct measurement of
      interaction forces between immobilized macromolecules, of their elastomechanical
      properties, etc. It is based on the covalent immobilization of amino group
      containing biomolecules (e.g., proteins, phospholipids) onto atomically flat gold
      surfaces via omega-functionalized self-assembled monolayers. We present the
      synthesis of the parent compound, dithio-bis(succinimidylundecanoate) (DSU), and
      a detailed study of the chemical and physical properties of the monolayer it
      forms spontaneously on Au(111). Scanning tunneling microscopy and atomic force
      microscopy (AFM) revealed a monolayer arrangement with the well-known depressions
      that are known to stem from an etch process during the self-assembly. The total
      density of the omega-N-hydroxysuccinimidyl groups on atomically flat gold was 585
      pmol/cm(2), as determined by chemisorption of (14)C-labeled DSU. This
      corresponded to approximately 75% of the maximum density of the omega
      unsubstituted alkanethiol. Measurements of the kinetics of monolayer formation
      showed a very fast initial phase, with total coverage within 30 S. A subsequent
      slower rearrangement of the chemisorbed molecules, as indicated by AFM, led to a
      decrease in the number of monolayer depressions in approximately 60 min. The rate
      of hydrolysis of the omega-N-hydroxysuccinimide groups at the monolayer/water
      interface was found to be very slow, even at moderately alkaline pH values.
      Furthermore, the binding of low-molecular-weight amines and of a model protein
      was investigated in detail.

PMID- 9172731
TI  - Single nuclear pores visualized by confocal microscopy and image processing.
AB  - How nuclear pore complexes, mediating the transport of nucleic acids, proteins,
      and metabolites between cell nucleus and cytoplasm, are arranged in the nuclear
      envelope is essentially unknown. Here we describe a method combining high
      resolution confocal imaging with image processing and pattern recognition to
      visualize single nuclear pore complexes (120 nm diameter), determine their
      relative positions with nanometer accuracy, and analyze their distribution in
      situ. The method was tested by means of a model system in which the very same
      sample areas could be imaged by confocal and electron microscopy. It was thus
      found that single fluorescent beads of 105 nm nominal diameter could be localized
      with a lateral accuracy of <20 nm and an axial accuracy of approximately 20 nm.
      The method was applied to digitonin-permeabilized 3T3 cells, whose nuclear pore
      complexes were fluorescently labeled with the anti-nucleoporin antibody mAb414.
      Stacks of optical sections were generated by confocal imaging at high resolution.
      Herein the nuclear pore complexes appeared as bright diffraction-limited spots
      whose centers were localized by fitting them by three-dimensional gaussians. The
      nearest-neighbor distribution function and the pair correlation function were
      calculated and found to agree well with those of randomly distributed hard
      cylinders of 138 +/- 17 nm diameter, but not with those of randomly distributed
      points or nonrandomly distributed cylinders. This was supported by a cluster
      analysis. Implications for the direct observation of the transport of single
      particles and molecules through individual nuclear pore complexes are discussed.

PMID- 9172732
TI  - Effects of variance in mini amplitude on stimulus-evoked release: a comparison of
      two models.
AB  - The strength of synaptic connections between two neurons is characterized by the
      number of release sites (N) on the presynaptic cell, the probability (p) of
      transmitter release at those sites in response to a stimulus, and the average
      size (A) of the postsynaptic response from each site. Quantal analysis can
      determine N, p, and A, but the large variance in the amplitudes of minis at
      central synapses is predicted to obscure quantal peaks and render quantal
      analysis unusable. Recently it has been suggested that the variance in mini
      amplitude is generated by differences between release sites, rather than by
      quantum-to-quantum fluctuations at identical sites, and that this form of
      variance in mini amplitude reduces the amount of variance expected in quantal
      peaks. Using simulations, we examine the possibility of resolving quantal peaks
      assuming either form of variance in mini amplitude. We find that individual
      quantal peaks are resolvable in neither case, provided that the uniquantal
      distribution is similar to the mini distribution. Because this lack of resolution
      compromises the utility of quantal analysis, we develop a general description
      that can solve N and p, given the statistical parameters of the mini distribution
      and the evoked distribution. We find that this description is relatively
      insensitive to the source of variance in mini amplitude.

PMID- 9172733
TI  - Structural fluctuations of myoglobin from normal-modes, Mossbauer, Raman, and
      absorption spectroscopy.
AB  - A normal-mode analysis of carbon monoxymyoglobin (MbCO) and deoxymyoglobin (Mb)
      with 170 water molecules is performed for (54)Fe and (57)Fe. A projection is
      defined that extracts iron out-of-plane vibrational modes and is used to
      calculate spectra that can be compared with those from resonance Raman
      scattering. The calculated spectra and the isotopic shift (57)Fe versus (54)Fe
      agree with the experimental data. At low temperatures the average mean square
      fluctuations (MSFs) of the protein backbone atoms agree with molecular dynamics
      simulation. Below 180 K the MSFs of the heme iron agree with the data from
      Mossbauer spectroscopy. The MSFs of the iron atom relative to the heme are an
      order of magnitude smaller than the total MSFs of the iron atom. They agree with
      the data from optical absorption spectroscopy. Thus the MSFs of the iron atom as
      measured by Mossbauer spectroscopy can be used to probe the overall motion of the
      heme within the protein matrix, whereas the Gaussian thermal line broadening of
      the Soret band and the resonance Raman bands can be used to detect local
      intramolecular iron-porphyrin motions.

PMID- 9172734
TI  - "Adaptive" behavior of ligand-gated ion channels: constraints by thermodynamics.
AB  - The calcium-induced calcium release channel of the cardiac sarcoplasmic reticulum
      has been reported to inactivate in a novel manner (termed "adaptation"), which
      permits reactivation by exposure to successively higher concentrations of
      calcium. I examined the limitations placed by thermodynamics on the possible
      kinetic mechanisms for such behavior. The mechanism suggested by Gyorke and Fill,
      in which the affinity of a calcium-binding site decreases during adaptation, is
      not thermodynamically feasible for a passive system, but requires an external
      input of free energy. Possible sources of such energy are 1) metabolic energy,
      which is excluded by the fact that adaptation was observed in isolated channels
      in the absence of ATP, or 2) coupling of ion permeation to gating, for which
      there is currently no evidence. I derived a general limit on the thermodynamic
      feasibility of a sequence of channel activations and adaptations, irrespective of
      channel kinetics, from the requirement that the free energy must decrease during
      the spontaneous evolution of the system from the state existing immediately after
      a step increase in [Ca2+] to the state of maximum open probability that follows.
      The opening of the channel must involve an increase in free energy, which must be
      compensated by the free energy released by the incremental binding of calcium.
      This requirement leads to a complicated system of inequalities, which was
      simplified and manipulated algebraically into the form of a linear programming
      problem. Numerical solution of this problem showed that the sequence of
      adaptations of the SR channel observed by Gyorke and Fill requires the presence
      of at least 10 calcium-binding sites on the channel if it is to occur in the
      absence of exogenous sources of free energy. This indicates either that a large
      number of calcium-binding sites participate in the regulation of the SR calcium
      release channel, or that the existing data are significantly flawed with respect
      to the low open probability in the resting state, the importance of "calcium
      spike" artifacts from flash photolysis, or both.

PMID- 9172735
TI  - Electrophysiological effects of ryanodine derivatives on the sheep cardiac
      sarcoplasmic reticulum calcium-release channel.
AB  - We have examined the effects of a number of derivatives of ryanodine on K+
      conduction in the Ca2+ release channel purified from sheep cardiac sarcoplasmic
      reticulum (SR). In a fashion comparable to that of ryanodine, the addition of
      nanomolar to micromolar quantities to the cytoplasmic face (the exact amount
      depending on the derivative) causes the channel to enter a state of reduced
      conductance that has a high open probability. However, the amplitude of that
      reduced conductance state varies between the different derivatives. In
      symmetrical 210 mM K+, ryanodine leads to a conductance state with an amplitude
      of 56.8 +/- 0.5% of control, ryanodol leads to a level of 69.4 +/- 0.6%, ester A
      ryanodine modifies to one of 61.5 +/- 1.4%, 9,21-dehydroryanodine to one of 58.3
      +/- 0.3%, 9 beta,21beta-epoxyryanodine to one of 56.8 +/- 0.8%, 9-hydroxy-21
      azidoryanodine to one of 56.3 +/- 0.4%, 10-pyrroleryanodol to one of 52.2 +/-
      1.0%, 3-epiryanodine to one of 42.9 +/- 0.7%, CBZ glycyl ryanodine to one of 29.4
      +/- 1.0%, 21-p-nitrobenzoyl-amino-9-hydroxyryanodine to one of 26.1 +/- 0.5%,
      beta-alanyl ryanodine to one of 14.3 +/- 0.5%, and guanidino-propionyl ryanodine
      to one of 5.8 +/- 0.1% (chord conductance at +60 mV, +/- SEM). For the majority
      of the derivatives the effect is irreversible within the lifetime of a single
      channel experiment (up to 1 h). However, for four of the derivatives, typified by
      ryanodol, the effect is reversible, with dwell times in the substate lasting tens
      of seconds to minutes. The effect caused by ryanodol is dependent on
      transmembrane voltage, with modification more likely to occur and lasting longer
      at +60 than at -60 mV holding potential. The addition of concentrations of
      ryanodol insufficient to cause modification does not lead to an increase in
      single-channel open probability, such as has been reported for ryanodine. At
      concentrations of > or = 500 mu M, ryanodine after initial rapid modification of
      the channel leads to irreversible closure, generally within a minute. In
      contrast, comparable concentrations of beta-alanyl ryanodine do not cause such a
      phenomenon after modification, even after prolonged periods of recording (>5
      min). The implications of these results for the site(s) of interaction with the
      channel protein and mechanism of the action of ryanodine are discussed. Changes
      in the structure of ryanodine can lead to specific changes in the
      electrophysiological consequences of the interaction of the alkaloid with the
      sheep cardiac SR Ca2+ release channel.

PMID- 9172736
TI  - Effects of injecting calcium-buffer solution on [Ca2+]i in voltage-clamped snail
      neurons.
AB  - We have investigated why fura-2 and Ca(2+)-sensitive microelectrodes report
      different values for the intracellular free calcium ion concentration ([Ca(2+)]i
      or its negative log, pCa(i)) of snail neurons voltage-clamped to -50 or -60 mV.
      Both techniques were initially calibrated in vitro, using calcium calibration
      solutions that had ionic concentrations similar to those of snail neuron
      cytoplasm. Pressure injections of the same solutions at resting and elevated
      [Ca(2+)]i were used to calibrate both methods in vivo. In fura-2-loaded cells
      these pressure injections generated changes in [Ca(2+)]i that agreed well with
      those expected from the in vitro calibration. Thus, using fura-2 calibrated in
      vitro, the average resting [Ca(2+)]i was found to be 38 nM (pCa(i) 7.42 +/-
      0.05). With Ca(2+)-sensitive microelectrodes, the first injection of calibration
      solutions always caused a negative shift in the recorded microelectrode
      potential, as if the injection lowered [Ca2+]i. No such effects were seen on the
      fura-2 ratio. When calibrated in vivo the Ca(2+)-sensitive microelectrode gave an
      average resting [Ca2+]i of approximately 25 nM (pCa(i) 7.6 +/- 0.1), much lower
      than when calibrated in vitro. We conclude that [Ca(2+)]i in snail neurons is
      approximately 40 nM and that Ca(2+)-sensitive microelectrodes usually cause a
      leak at the point of insertion. The effects of the leak were minimized by
      injection of a mobile calcium buffer.

PMID- 9172737
TI  - Vectorially oriented monolayers of detergent-solubilized Ca(2+) -ATPase from
      sarcoplasmic reticulum.
AB  - A method for tethering proteins to solid surfaces has been utilized to form
      vectorially oriented monolayers of the detergent-solubilized integral membrane
      protein Ca(2+) -ATPase from the sarcoplasmic reticulum (SR). Bifunctional,
      organic self-assembled monolayers (SAMs) possessing "headgroup" binding
      specificity for the substrate and "endgroup" binding specificity for the enzyme
      were utilized to tether the enzyme to the substrate. Specifically, an amine
      terminated 11-siloxyundecaneamine SAM was found to bind the Ca(2+)-ATPase
      primarily electrostatically. The Ca(2+)-ATPase was labeled with the fluorescent
      probe 5-(2-[(iodoacetyl)amino]ethyl)aminonaphthalene-1-sulfonic acid before
      monolayer formation. Consequently, fluorescence measurements performed on amine
      terminated SAM/enzyme monolayers formed on quartz substrates served to establish
      the nature of protein binding. Formation of the monolayers on inorganic
      multilayer substrates fabricated by molecular beam epitaxy made it possible to
      use x-ray interferometry to determine the profile structure for the system, which
      was proved correct by x-ray holography. The profile structures established the
      vectorial orientation of the Ca(2+)-ATPase within these monolayers, to a spatial
      resolution of approximately 12 A. Such vectorially oriented monolayers of
      detergent-solubilized Ca(2+)-ATPase from SR make possible a wide variety of
      correlative structure/function studies, which would serve to elucidate the
      mechanism of Ca(2+) transport by this enzyme.

PMID- 9172738
TI  - Voltage-dependent modulation of single N-Type Ca2+ channel kinetics by receptor
      agonists in IMR32 cells.
AB  - The voltage-dependent inhibition of single N-type Ca(2+) channels by
      noradrenaline (NA) and the delta-opioid agonist D-Pen(2)-D-Pen (5)-enkephalin
      (DPDPE) was investigated in cell-attached patches of human neuroblastoma IMR32
      cells with 100 mM Ba(2+) and 5 microM nifedipine to block L-type channels. In 70%
      of patches, addition of 20 microM NA + 1 microM DPDPE delayed markedly the first
      channel openings, causing a four- to fivefold increase of the first latency at
      +20 mV. The two agonists or NA alone decreased also by 35% the open probability
      (P(o)), prolonged partially the mean closed time, and increased the number of
      null sweeps. In contrast, NA + DPDPE had little action on the single-channel
      conductance (19 versus 19.2 pS) and minor effects on the mean open time.
      Similarly to macroscopic Ba(2+) currents, the ensemble currents were fast
      activating at control but slowly activating and depressed with the two agonists.
      Inhibition of single N-type channels was effectively removed (facilitated) by
      short and large depolarizations. Facilitatory pre-pulses increased P(o)
      significantly and decreased fourfold the first latency. Ensemble currents were
      small and slowly activating before pre-pulses and became threefold larger and
      fast decaying after facilitation. Our data suggest that slowdown of Ca(2+)
      channel activation by transmitters is mostly due to delayed transitions from a
      modified to a normal (facilitated) gating mode. This single-channel gating
      modulation could be well simulated by a Monte Carlo method using previously
      proposed kinetic models predicting marked prolongation of first channel openings.

PMID- 9172739
TI  - Nicotinic acetylcholine receptor channels are influenced by the physical state of
      their membrane environment.
AB  - We investigated the effect of the physical state of the cell membrane on the
      activity of the nicotinic acetylcholine receptor (AChR) in various clonal cell
      lines transfected with the cDNAs of embryonic or adult AChR by measuring single
      channel properties and some membrane physicochemical properties as a function of
      temperature. Unitary conductance and channel closing rate, alpha, had Q(10)
      values of 1.2 and 2.2, respectively. Using Eyring's transition state theory, it
      was calculated that both embryonic and adult-type AChR had relatively low thermal
      sensitivity of ionic conductance and activation energy (E(a) of 3.0-5.0 kcal-mol(
      1) at 20 degrees C), indicating that once the AChR channel opens, ion movement is
      dominated by diffusional processes. Channel closure exhibited higher energy
      requirements, with E(a) values of about 13 kcal-mol(-1). This process appears to
      be more endothermic (higher delta H(a) values) than ion permeation, and it is
      plausible that the energy acquired by the system can be used in the maintenance
      of its degree of order, as revealed by the delta S(a) 0 calculated for channel
      closure. The influence of the membrane environment on AChR function is reinforced
      by the observation that the conductance of the same, embryonic-type AChR protein,
      expressed in qualitatively different cellular lipid environments, appeared to
      have different energetic requirements. A correlation between the
      electrophysiological and thermodynamic parameters of the AChR and physicochemical
      properties of the membrane bilayer in which the protein is embedded could be
      established using measurements of the so-called generalized polarization (GP) of
      the lipophilic probe laurdan. Both embryonic and adult AChR exhibited a higher GP
      and a higher sensitivity to temperature-dependent changes in GP when
      heterologously expressed in stable form in Chinese hamster ovary (CHO)-derived
      cells than did the native embryonic AChR in BC3H-1 cells, indicating that these
      two properties are determined by the host membrane and are not inherent
      properties of the AChR type. In addition, the differences in the macroscopic
      physical states of the lipids and membrane-associated solvent (water) dipolar
      relaxation between BC3H-1 and CHO-derived cells indicated by the spectroscopic
      properties of laurdan suggest that both lipid and associated water may influence
      the microscopic activity of individual AChR molecules embedded in the lipid
      bilayer. Finally, the different dependence of AChR channel conductance and mean
      open time as a function of GP observed between the different AChR subtypes in
      clonal cell lines suggests the importance of specific lipid-protein interactions
      in addition to bulk membrane properties.

PMID- 9172740
TI  - Simultaneous measurement of Ca2+ influx and reversal potentials in recombinant N
      methyl-D-aspartate receptor channels.
AB  - The Ca(2+) permeability of N-methyl-D-aspartate receptor (NMDA-R) channels was
      studied in human embryonic kidney cells transfected with the NR1-NR2A subunit
      combination. To determine the fractional Ca(2+) current (P(f)), measurements of
      fura-2-based Ca(2+) influx and whole-cell currents were made in symmetrical
      monovalent ion concentrations at membrane potentials between -50 mV and the
      reversal potential. The ratios of Ca(2+) flux over net whole-cell charge at 2, 5,
      and 10 mM external Ca(2+) concentrations ([Ca](o)) were identical at a membrane
      potential close to the reversal potential of the monovalent current component.
      Assuming unity of P(f) at this potential, the percentage of current carried by
      Ca(2+) was found to be 18.5 +/- 1.3% at 2 mM [Ca](o) and -50 mV. This value,
      which is higher than the ones reported previously, was confirmed in independent
      experiments in which a pure flux of Ca(2+) through NMDA-R channels was used to
      calibrate the Ca(2+) influx signals. The measured values of fractional Ca(2+)
      currents, which agree with the predictions of the Goldman-Hodgkin-Katz equations,
      are also compatible with a two-barrier model for ion permeation, in which the
      differences between the energy barriers for Ca(2+) and monovalent ions are
      similar on the external and internal membrane sides.

PMID- 9172741
TI  - Accounting for the shapes and size distributions of miniature endplate currents.
AB  - The current model does not account adequately for the characteristics of
      miniature endplate currents (MEPCs). We do not understand their relatively slow
      rise, the shape of their rise, their variable and sometimes prolonged decay, and
      the correlation between amplitude and decay time. If we assume that ACh is
      released from the vesicle through a pore and that the vesicle enlarges as it
      takes on additional transmitter, the predictions are more like MEPCs. However,
      previous measurements showed that after quantal size was increased the vesicles
      in the terminal were not enlarged. This need not be a problem, because some of
      the ACh is added to vesicles positioned at the active zones, a process known as
      second-stage loading. By using the false transmitter precursor monoethylcholine
      we provide additional evidence for second-stage loading. The distribution of
      quantal sizes at the junction usually does not follow a normal probability
      distribution; it is skewed to the right. The skew can be accounted for by a model
      incorporating second-stage loading in which the vesicles are released randomly,
      without regard to their ACh content. If the vesicles increase in size when they
      contain more transmitter, only vesicles at the active zone need swell.

PMID- 9172742
TI  - Characteristics of the binding of tacrine to acidic phospholipids.
AB  - Tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrate) is an inhibitor of
      acetylcholinesterase currently used in the treatment of the symptoms of
      Alzheimer's disease. The present study demonstrates preferential binding of this
      drug to acidic phospholipids, as revealed by fluorescence polarization,
      penetration into lipid monolayers, and effects on the thermal phase behavior of
      dimyristoyl phosphatidic acid (DMPA). A fivefold enhancement in the polarization
      of tacrine emission is evident above the main phase transition temperature (T(m))
      of DMPA vesicles, whereas below T(m) only a 0.75-fold increase is observed. In
      contrast, the binding of tacrine to another acidic phospholipid,
      dimyristoylphosphatidylglycerol, did not exhibit strong dependence on T(m). In
      accordance with the electrostatic nature of the membrane association of tacrine,
      the extent of binding was augmented with increasing contents of egg PG in
      phosphatidylcholine liposomes. Furthermore, [NaCl] > 50 mM dissociates tacrine
      (albeit incompletely) from the liposomes composed of acidic phospholipids.
      Inclusion of the cationic amphiphile sphingosine in egg PG vesicles decreased the
      membrane association of tacrine until at 1:1 sphingosine: egg PG stoichiometry
      binding was no longer evident. Tacrine also penetrated into egg PG but not into
      egg PC monolayers. Together with broadening of the main transition and causing a
      shoulder on its high temperature side, the binding of tacrine to DMPA liposomes
      results in a concentration-dependent reduction both in the combined enthalpy
      delta H of the above overlapping endotherms and the main transition temperature
      T(m). Interestingly, these changes in the thermal phase behavior of DMPA as a
      function of the content of the drug in vesicles were strongly nonlinear. More
      specifically, upon increasing [tacrine], T(m) exhibited stepwise decrements.
      Simultaneously, sharp minima in delta H were observed at drug:lipid
      stoichiometries of approximately 2:100 and 25:100, whereas a sharp maximum in
      delta H was evident at 18:100. The above results are in keeping with tacrine
      causing phase separation processes in the bilayer and may also relate to
      microscopic drug-induced ordering processes within the membrane.

PMID- 9172743
TI  - Influence of lipid chain unsaturation on melittin-induced micellization.
AB  - It is well known that melittin, an amphipathic helical peptide, causes the
      micellization of phosphatidylcholine vesicles. In the present work, we conclude
      that the extent of micellization is dependent on the level of unsaturation of the
      lipid acyl chains. We report the results obtained on two systems:
      dipalmitoylphosphatidylcholine (DPPC), containing 10(mol)% saturated or
      unsaturated fatty acid (palmitic, oleic, or linoleic), and DPPC, containing
      10(mol)% positively charged diacyloxy-3-(trimethylammonio)propane bearing
      palmitic or oleic acyl chains. For both systems, the presence of unsaturation in
      the lipid acyl chains inhibits melittin-induced micellization. Conversely, the
      addition of saturated palmitic acid to the DPPC matrix enhances the
      micellization. This modulation is proposed to be associated with the cohesion of
      the hydrophobic core. When the lipid chain packing of the gel-phase bilayer is
      already perturbed by the presence of unsaturation, it seems easier for the
      membrane to accommodate melittin at the interface, and the distribution of the
      peptide in the bilayer could be the origin of the inhibition of the
      micellization. The cohesion of the apolar core is shown to play an unquestionable
      role in melittin-induced micellization; however, this contribution does not
      appear to be as important as the electrostatic interactions between melittin and
      positively or negatively charged lipids.

PMID- 9172744
TI  - Interaction between model membranes and a new class of surfactants with
      antioxidant function.
AB  - The effect of two series of amphiphilic quaternary ammonium salts on some
      properties of phospholipid membranes was studied. The compounds of one series, N
      benzyl-N,N-dimethyl-N-alkyl ammonium bromides, exert a destructive effect on
      membranes and are treated as reference compounds. The compounds of the other
      series, N-(3,5-di-t-butyl-4-hydroxy)benzyl-N,N-dimethyl-N-alkyl ammonium
      bromides, are derivatives of the former ones, exhibit antioxidant properties, and
      do only relatively slight damage to the membranes. The aim of the work was to
      explain the difference in molecular interaction with membranes between the two
      kinds of hydrophobic compounds. Thermodynamic methods, a new mixing technique,
      and monolayer and quantum calculation methods were used. It has been shown that
      the antioxidant molecules are less hydrophobic than those of the reference
      compounds and disturb the membrane organization to a lesser extent. On the basis
      of monolayer data, we suggest that the studied antioxidant behaves like a
      substitutional impurity, whereas the reference behaves like an interstitial one.

PMID- 9172745
TI  - Free radical mediated x-ray damage of model membranes.
AB  - The damaging effects of synchrotron-derived x rays on aqueous phospholipid
      dispersions have been evaluated. The effect of degree of lipid hydration,
      phospholipid chemical structure, mesophase identity, aqueous medium composition,
      and incident flux on the severity and progress of damage was quantified using
      time-resolved x-ray diffraction and chromatographic analysis of damage products.
      Electron spin resonance measurements of spin-trapped intermediates generated
      during irradiation suggest a free radical-mediated process. Surprisingly,
      radiation damage effects revealed by x-ray diffraction were imperceptible when
      the lamellar phases were prepared under water-stressed conditions, despite the
      fact that x-ray-induced chemical breakdown of the lipid occurred regardless of
      hydration level. Of the fully hydrated lipid systems studied, saturated diacyl
      phosphatidylcholines were most sensitive to radiation damage compared to the
      ester- and ether-linked phosphatidylethanolamines and the ether-linked
      phosphatidylcholines. The inclusion of buffers or inorganic salts in the
      dispersing medium had only a minor effect in reducing damage development. A small
      inverse dose-rate effect was found when the x-ray beam intensity was changed 15
      fold. These results contribute to our understanding of the mechanism of radiation
      damage, to our appreciation of the importance of monitoring both structure and
      composition when evaluating biomaterials radiation sensitivity, and to the
      development of strategies for eliminating or reducing the severity of damage due
      to an increasingly important source of x rays, synchrotron radiation. Because
      damage is shown to be free radical mediated, these results have an important
      bearing on age-related accumulation of free radicals in cells and how these might
      compromise membrane integrity, culminating in cell death.

PMID- 9172746
TI  - Structure and dynamics of melittin in lysomyristoyl phosphatidylcholine micelles
      determined by nuclear magnetic resonance.
AB  - Mixed micelles of the 26-residue, lytic peptide melittin (MLT) and 1-myristoyl-2
      hydroxyl-sn-glycero-3-phosphocholine (MMPC) in aqueous solution at 25 degrees C
      were investigated by (13)C- and (31)P-NMR spectroscopy. (13)C alpha chemical
      shifts of isotopically labeled synthetic MLT revealed that MLT in the micelle is
      predominantly alpha-helical and that the peptide secondary structure is stable
      from pH 4 to pH 11. Although the helical transformation of MLT as determined from
      NMR is evident at lipid:peptide molar ratios as low as 1:2, tryptophan
      fluorescence measurements demonstrate that well-defined micellar complexes do not
      predominate until lipid:peptide ratios exceed 30:1. (31)P linewidth measurements
      indicate that the interaction between phosphate ions in solution and cationic
      groups on MLT is pH dependent, and that the phosphoryl group of MMPC senses a
      constant charge, most likely +2, on MLT from pH 4 to pH 10. (13)C-NMR relaxation
      data, analyzed using the model-free formalism, show that the peptide backbone of
      MLT is partially, but not completely, immobilized in the mixed micelles.
      Specifically, order parameters (S(2)) of C alpha-H vectors averaged 0.7 and were
      somewhat larger for residues in the N-terminal half of the molecule. The amino
      terminal glycine had essentially the same range of motion as the backbone
      carbons. Likewise, order parameters for the trp side chain were similar to those
      found for the peptide C alpha moieties, as was verified by trp fluorescence
      anisotropy decay data. In contrast, the motion of the lysine side chains was less
      restricted, the average S(2) values for the C epsilon-H vectors being 0.19, 0.30,
      and 0.44 for lys-7, 21, and 23, respectively, for MLT in the mixed micelles.
      Values of the effective correlation time of the local motion tau e were in the
      motional narrowing limit and usually longer for side-chain atoms than for those
      in the backbone. The dynamics were independent of pH from pH 4 to pH 9, but at pH
      11 the correlation time for the rotational motion of the mixed micelles as a
      whole increased from 10 ns to 16 ns, and S(2) for the lys side chains increased.
      Overall it appears that the MLT helix lies near the surface of the micelle at low
      to neutral pH, but at higher pH its orientation changes, accompanied by deeper
      penetration of the lysine side chains into the micelle interior. It is apparent,
      however, that the MLT-lipid interaction is not dependent on deprotonation of any
      of the titratable cationic groups in the peptide in the pH 4-10 range, and that
      there is substantial backbone and side-chain mobility in micelle-bound MLT.

PMID- 9172747
TI  - Critical micelle concentrations and stirring are rate limiting in the loss of
      lipid mass during membrane degradation by phospholipase A2.
AB  - In phospholipid membranes attacked by phospholipase A(2) (PLA(2)), accumulation
      of degradation products influences the binding affinity as well as the catalytic
      activity of PLA(2). Such accumulation in its turn depends on the rate of membrane
      degradation and the efflux of degradation products from the membrane, the latter
      being influenced by the stirring conditions in the system. This complicated
      process was investigated with a new ellipsometric technique for in situ
      measurement of membrane mass in a well-defined flow system. Planar phospholipid
      bilayers were formed on rotating silicon discs in buffer solution. After the
      addition of 0.05-100 ng/ml of PLA(2) (from Naja mocambique mocambique) to the
      buffer, mass desorption could be measured with a precision of 3-5 ng/cm(2), that
      is, about 1% of the surface mass of a single bilayer. Using radiolabeled
      phospholipids and thin-layer chromatography, it was verified that only the
      degradation products desorb from the membrane, which was confirmed by the
      desorption of mixtures of phospholipids, lysophospholipids, and fatty acids. The
      rotating disc allows the exact calculation of the mass transfer constant for
      transport-limited exchange of lipid between fluid and disc surface, as a function
      of rotation rate. By using the mass transfer constant, the critical micelle
      concentrations, and the mole fractions of products, desorption kinetics could be
      fully described. The amount of degraded phospholipid could be continuously
      monitored as the sum of the product mass still present in the membrane, as
      inferred from the desorption rate, and the mass already lost from the surface. It
      is concluded that ellipsometry is a suitable tool for studying the effects of
      PLA(2) on membranes.

PMID- 9172748
TI  - Intrinsic curvature in normal and inverted lipid structures and in membranes.
AB  - The intrinsic or spontaneous radius of curvature, R(o), of lipid monolayer
      assemblies is expressed in terms of a lipid molecular packing parameter, V/AI,
      for various geometries. It is shown that the equivalent lipid length, 1, in
      inverted hexagonal (HII) phases, defined by a cylindrical shell of equal total
      lipid volume, yields an expression for R o identical to that for inverted
      cylindrical micelles (or, equivalently, HII phases in the presence of excess
      hydrocarbon). This identity is used to obtain values of the effective packing
      parameter for various phosphatidylethanolamines. The temperature dependence of
      the intrinsic radius of curvature is predicted to be negative and to be
      considerably greater than that for the lipid length in nearly all cases. The
      thermal expansion coefficient is not constant but is found to vary, depending on
      the value of the lipid packing parameter. A possible addition rule is constructed
      for the intrinsic radius of curvature of lipid mixtures, based on the linear
      additivity of the effective molecular volumes, V, and molecular areas, A. This
      relation is found to hold for mixtures of dioleoyl phosphatidylcholine (DOPC)
      with dioleoyl phosphatidylethanolamine, and a value of R(o) of > or = 9 A (V/AI =
      1.08) is obtained for DOPC. The energetics of the intrinsic curvature and
      lamellar-nonlamellar transitions are also discussed within the framework of the
      model.

PMID- 9172749
TI  - Interactions of N-stearoyl sphingomyelin with cholesterol and
      dipalmitoylphosphatidylcholine in bilayer membranes.
AB  - Differential scanning calorimetry and x-ray diffraction have been utilized to
      investigate the interaction of N-stearoylsphingomyelin (C18:0-SM) with
      cholesterol and dipalmitoylphosphatidylcholine (DPPC). Fully hydrated C18:0-SM
      forms bilayers that undergo a chain-melting (gel -->liquid-crystalline)
      transition at 45 degrees C, delta H = 6.7 kcal/mol. Addition of cholesterol
      results in a progressive decrease in the enthalpy of the transition at 45 degrees
      C and the appearance of a broad transition centered at 46.3 degrees C; this
      latter transition progressively broadens and is not detectable at cholesterol
      contents of >40 mol%. X-ray diffraction and electron density profiles indicate
      that bilayers of C18:0-SM/cholesterol (50 mol%) are essentially identical at 22
      degrees C and 58 degrees C in terms of bilayer periodicity (d = 63-64 A), bilayer
      thickness (d rho-p = 46-47 A), and lateral molecular packing (wide-angle
      reflection, 1/4.8 A-(1)). These data show that cholesterol inserts into C18:0-SM
      bilayers, progressively removing the chain-melting transition and altering the
      bilayer structural characteristics. In contrast, DPPC has relatively minor
      effects on the structure and thermotropic properties of C18:0-SM. DPPC and C18:0
      SM exhibit complete miscibility in both the gel and liquid-crystalline bilayer
      phases, but the pre-transition exhibited by DPPC is eliminated at >30 mol% C18:0
      SM. The bilayer periodicity in both the gel and liquid-crystalline phases
      decreases significantly at high DPPC contents, probably reflecting differences in
      hydration and/or chain tilt (gel phase) of C18:0-SM and DPPC.

PMID- 9172750
TI  - Inner sarcolemmal leaflet Ca(2+) binding: its role in cardiac Na/Ca exchange.
AB  - A recently completed model of Ca concentration and movements in the cardiac cell
      diadic cleft space predicts that removal or neutralization of inner sarcolemmal
      (SL) leaflet anionic Ca-binding sites at the sarcolemmal border of this space
      will greatly diminish Na/Ca exchange-mediated Ca efflux. The present study tests
      this prediction using the local anesthetic dibucaine as a probe. It is shown, in
      isolated SL, that dibucaine competitively displaces Ca specifically from anionic
      phospholipid headgroups. Dibucaine also displaces Ca from the SL when applied to
      intact cells. It does not affect the content or release of Ca from sarcoplasmic
      reticulum (SR) in these cells. This eliminates a primary effect on SR Ca as a
      contributing factor to dibucaine's effect on Na/Ca exchange-mediated Ca efflux.
      Measurement of this efflux from whole cells shows a highly significant reduction
      of 58% (p < 0.001) by 0.5 mM dibucaine. The inhibiting effect of dibucaine on
      Na/Ca exchange-mediated Ca efflux can be significantly reversed by augmentation
      of Ca release from SR by caffeine at the time of activation of Na/Ca exchange.
      This supports the contention that the dibucaine-SL interaction is a competitive
      one vis-a-vis Ca. The results are supportive of the model in which inner SL
      leaflet Ca-binding sites account for the delay of Ca diffusion from the diadic
      cleft, thereby prolonging the time for which [Ca] remains elevated in the cleft.
      The prolonged increased [Ca] significantly enhances the ability of Na/Ca exchange
      to remove Ca from the cell during the excitation-contraction cycle.

PMID- 9172751
TI  - Effect of the N-terminal glycine on the secondary structure, orientation, and
      interaction of the influenza hemagglutinin fusion peptide with lipid bilayers.
AB  - The amino-terminal segment of the membrane-anchored subunit of influenza
      hemagglutinin (HA) plays a crucial role in membrane fusion and, hence, has been
      termed the fusion peptide. We have studied the secondary structure, orientation,
      and effects on the bilayer structure of synthetic peptides corresponding to the
      wild-type and several fusogenic and nonfusogenic mutants with altered N-termini
      of the influenza HA fusion peptide by fluorescence, circular dichroism, and
      Fourier transform infrared spectroscopy. All peptides contained segments of alpha
      helical and beta-strand conformation. In the wild-type fusion peptide, 40% of all
      residues were in alpha-secondary and 30% in beta-secondary structures. By
      comparison, the nonfusogenic peptides exhibited larger beta/alpha secondary
      structure ratios. The order parameters of the helices and the amide carbonyl
      groups of the beta-strands of the wild-type fusion peptide were measured
      separately, based on the infrared dichroism of the respective absorption bands.
      Order parameters in the range 0.1-0.7 were found for both segments of the wild
      type peptide, which indicates that they are most likely aligned at oblique angles
      to the membrane normal. The nonfusogenic but not the fusogenic peptides induced
      splitting of the infrared absorption band at 1735 cm(-1), which is assigned to
      stretching vibrations of the lipid ester carbonyl bond. This splitting, which
      reports on an alteration of the hydrogen bonds formed between the lipid ester
      carbonyls and water and/or hydrogen-donating groups of the fusion peptides,
      correlated with the beta/alpha ratio of the peptides, suggesting that unpaired
      beta-strands may replace water molecules and hydrogen-bond to the lipid ester
      carbonyl groups. The profound structural changes induced by single amino acid
      replacements at the extreme N-terminus of the fusion peptide further suggest that
      tertiary or quaternary structural interactions may be important when fusion
      peptides bind to lipid bilayers.

PMID- 9172752
TI  - Effects of unsaturation and curvature on the transverse distribution of
      intramolecular dynamics of dipyrenyl lipids.
AB  - The roles of acyl chain unsaturation and curvature in the excimer formation
      efficiency (EFE) of site-specific conjugated pyrene molecules in lipid membranes
      have been investigated by steady-state and time-resolved fluorescence
      spectroscopy. Six 1-2-(pyrenyl-n-acyl)-phosphatidylcholine (dipy(n)PC) probes,
      with pyrenyl chains of varying methylene units n from 4 to 14 carbons, were
      incorporated separately into dioleoylphosphatidylcholine (DOPC) or
      dioleoylphosphatidylethanolamine (DOPE) lipid membranes at 0.1 mol%. Both the
      excimer-to-monomer fluorescence intensity ratio and association-to-dissociation
      rate constant ratio of conjugated pyrenes were used to quantify EFE. At all
      temperatures (T = 0-30 degrees C) and for n = 4 and 6, the EFE for DOPE was
      always smaller than EFE for DOPC. At T < 10 degrees C (where DOPE and DOPC are in
      the liquid crystalline L alpha phase) and for n > 8, the EFE for curvature
      frustrated DOPE was significantly greater than EFE for nonfrustrated DOPC
      (control), and the difference increased gradually with n. At T> 18 degrees C
      (where DOPE is in the inverted hexagonal H(II) phase and DOPC is in the L alpha
      phase) and for n > 8, EFE for the curvature-relaxed DOPE was again smaller than
      the EFE for DOPC control. The contributions of splay conformation and internal
      dynamics of pyrenyl chains to EFE were examined separately using a lattice model.
      Our results suggest that i) the cis double bonds of the host lipid matrix
      strongly perturb both the conformation and dynamics of conjugated pyrenes at the
      specific location around n = 8, and ii) the lateral stress at the upper part (n <
      8) of the curvature frustrated bilayer membranes (DOPE) may be significantly
      relaxed once the membrane surface adopts a favorable negative interfacial
      curvature.

PMID- 9172753
TI  - Diacylglycerol and the promotion of lamellar-hexagonal and lamellar-isotropic
      phase transitions in lipids: implications for membrane fusion.
AB  - Changes in steady-state fluorescence anisotropy of 1 -(4-trimethylaminophenyl)-6
      phenyl-1,3,5-hexatriene TMA-DPH) are applied to the detection of lamellar
      hexagonal transitions in egg phosphatidylethanolamine. Even low (2 mole%)
      proportions of diacylglycerol decrease the hexagonal transition temperature
      considerably, as confirmed by differential scanning calorimetry. Diacylglycerol
      is also found to promote a lamellar to "isotropic" (Q(224) cubic) transition in
      mixtures of phosphatidylcholine: phosphatidylethanolamine:cholesterol. This
      nonreversible transition is also observed by (31)P nuclear magnetic resonance and
      detected as a large increase in TMA-DPH steady-state anisotropy. The same
      technique reveals as well that lysophosphatidylcholine counteracts the effect of
      diacylglycerol and stabilizes the lamellar phase in both transitions.
      Diacylglycerol and lysophosphatidylcholine are known to respectively promote and
      inhibit membrane fusion in a variety of systems. These data are interpreted in
      support of the hypothesis of a highly bent structural fusion intermediate
      ("stalk"). They also show the interest of lipid-phase studies in predicting and
      rationalizing membrane fusion mechanisms.

PMID- 9172754
TI  - Alcohol binding to liposomes by 2H NMR and radiolabel binding assays: does
      partitioning describe binding?
AB  - Implicit within the concept of membrane-buffer partition coefficients of solutes
      is a nonspecific solvation mechanism of solute binding. However, (2)H NMR studies
      of the binding of (2)H(6)-ethanol and [1-(2)H(2)] n-hexanol to
      phosphatidylcholine vesicles have been interpreted as evidence for two distinct
      alcohol binding modes. One binding mode was reported to be at the membrane
      surface. The second mode was reported to be within the bilayer interior. An
      examination of the (2)H NMR binding studies, together with direct radiolabel
      binding assays, shows that other interpretations of the data are more plausible.
      The results are entirely consistent with partitioning (nonspecific binding) as
      the sole mode of alcohol binding to liposomes, in accord with our previous
      thermodynamic interpretation of alcohol action in phosphatidylcholine liposomes.

PMID- 9172756
TI  - Diffusion of fluorescently labeled macromolecules in cultured muscle cells.
AB  - Myotubes were obtained from culture of satellite cells. They had a sarcomeric
      organization similar to that of muscle. The diffusion in the direction
      perpendicular to the fibers of microinjected fluorescein isothiocyanate-dextrans
      of molecular weight ranging from 9500 to 150,000 was examined by modulated fringe
      pattern photobleaching. On the time scale of the observation, 10-30 S, all of the
      dextrans were completely mobile in the cytoplasm. The diffusion coefficients were
      compared to the values obtained in water. The ratio D(cytoplasm)/D(w) decreased
      with the hydrodynamic radius R(h) of the macromolecules. The mobility of inert
      molecules in muscle cells is hindered by both the crowding of the fluid phase of
      the cytoplasm and the screening effect due to myofilaments: D(cytoplasm)/D(w) =
      (D/D(w)) protein crowding x (D/D(w))(filament screening). The equation
      (D/D(w))filament screening = exp(-K(L)RCh) was used for the contribution of the
      filaments to the restriction of diffusion. A free protein concentration of 135
      mg/ml, a solvent viscosity of cytoplasm near that of bulk water, and a calculated
      K(L) of 0.066 nm(-1), which takes into account the sarcomeric organization of
      filaments, accurately represent our data.

PMID- 9172755
TI  - Phosphate release and force generation in cardiac myocytes investigated with
      caged phosphate and caged calcium.
AB  - The phosphate (P(i)) dissociation step of the cross-bridge cycle was investigated
      in skinned rat ventricular myocytes to examine its role in force generation and
      Ca(2+) regulation in cardiac muscle. Pulse photolysis of caged P(i) (alpha
      carboxyl-2-nitrobenzyl phosphate) produced up to 3 mM P(i) within the filament
      lattice, resulting in an approximately exponential decline in steady-state
      tension. The apparent rate constant, k (rho i), increased linearly with total
      P(i) concentration (initial plus photoreleased), giving an apparent second-order
      rate constant for P(i) binding of 3100 M(-1) s(-1), which is intermediate in
      value between fast and slow skeletal muscles. A decrease in the level of Ca(2+)
      activation to 20% of maximum tension reduced k (rho i) by twofold and increased
      the relative amplitude by threefold, consistent with modulation of P(i) release
      by Ca2+. A three-state model, with separate but coupled transitions for force
      generation and P(i) dissociation, and a Ca(2+)-sensitive forward rate constant
      for force generation, was compatible with the data. There was no evidence for a
      slow phase of tension decline observed previously in fast skeletal fibers at low
      Ca(2+), suggesting differences in cooperative mechanisms in cardiac and skeletal
      muscle. In separate experiments, tension development was initiated from a relaxed
      state by photolysis of caged Ca(2+). The apparent rate constant, k(Ca), was
      accelerated in the presence of high P(i) consistent with close coupling between
      force generation and P(i) dissociation, even when force development was initiated
      from a relaxed state. k(Ca) was also dependent on the level of Ca(2+) activation.
      However, significant quantitative differences between k (rho i) and k(Ca),
      including different sensitivities to Ca(2+) and P(i) indicate that caged Ca(2+)
      tension transients are influenced by additional Ca(2+)-dependent but P i
      independent steps that occur before P(i) release. Data from both types of
      measurements suggest that kinetic transitions associated with P(i) dissociation
      are modulated by the Ca(2+) regulatory system and partially limit the
      physiological rate of tension development in cardiac muscle.

PMID- 9172758
TI  - Fluorescence anisotropy of DNA/DAPI complex: torsional dynamics and geometry of
      the complex.
AB  - Fluorescence depolarization of synthetic polydeoxynucleotide/4'-6-diamidino-2
      phenylindole dihydrochloride complexes has been investigated as a function of
      dye/polymer coverage. At low coverage, fluorescence depolarization is due to
      local torsional motions of the DNA segment where the dye resides. At relatively
      high coverage, fluorescence depolarization is dominated by energy transfer to
      other dye molecules along the DNA. The extent of the observed depolarization due
      to torsional motion depends on the angle the dye molecule forms with the DNA
      helical axis. A large torsional motion and a small angle produce the same
      depolarization as a small torsional motion and a large projection angle.
      Furthermore, the extent of transfer critically depends on the relative
      orientation of dye molecules along the DNA. The effect of multiple transfer is
      examined using a Monte Carlo approach. The measurement of depolarization with
      transfer, at high coverage, allows determination of the dye orientation about the
      DNA helical axis. The value of the torsional spring constant is then determined,
      at very low coverage, for few selected polydeoxynucleotides.

PMID- 9172757
TI  - Myosin regulatory light chain modulates the Ca2+ dependence of the kinetics of
      tension development in skeletal muscle fibers.
AB  - To determine the role of myosin regulatory light chain (RLC) in modulating
      contraction in skeletal muscle, we examined the rate of tension development in
      bundles of skinned skeletal muscle fibers as a function of the level of Ca(2+)
      activation after UV flash-induced release of Ca(2+) from the photosensitive
      Ca(2+) chelator DM-nitrophen. In control fiber bundles, the rate of tension
      development was highly dependent on the concentration of activator Ca(2+) after
      the flash. There was a greater than twofold increase in the rate of tension
      development when the post-flash [Ca(2+)] was increased from the lowest level
      tested (which produced a steady tension that was 42% of maximum tension) to the
      highest level (producing 97% of maximum tension). However, when 40-70% of
      endogenous myosin RLC was extracted from the fiber bundles, tension developed at
      the maximum rate, regardless of the post-flash concentration of Ca(2+). Thus, the
      Ca(2+) dependence of the rate of tension development was eliminated by partial
      extraction of myosin RLC, an effect that was partially reversed by recombination
      of RLC back into the fiber bundles. The elimination of the Ca(2+) dependence of
      the kinetics of tension development was specific to the extraction of RLC rather
      than an artifact of the co-extraction of both RLC and Troponin C, because the
      rate of tension development was still Ca(2+) dependent, even when nearly 50% of
      endogenous Troponin C was extracted from fiber bundles fully replete with RLC.
      Thus, myosin RLC appears to be a key component in modulating Ca(2+) sensitive
      cross-bridge transitions that limit the rate of force development after
      photorelease of Ca(2+) in skeletal muscle fibers.

PMID- 9172759
TI  - Reorientations in the bacteriorhodopsin photoscycle are pH dependent.
AB  - Chromophore reorientations during the bacteriorhodopsin photocycle in the purple
      membrane of Halobacterium salinarium have been detected by time-resolved linear
      dichroism measurements of the optical anisotropy over the pH range from 4 to 10
      and at ionic strengths from 10 mM to 1 M. The results show that reorientations in
      the L and M states of bacteriorhodopsin are pH dependent, reaching their largest
      amplitude when the membrane is at pH 6-8. Reorientations on the millisecond time
      scale of unexcited spectator proteins in the native purple membrane also depend
      on pH, consistent with the suggestion that spectator reorientations are triggered
      by reorientation of the photoexcited protein. The results imply that a group with
      a PK(a) of 5 to 6 enables reorientations, and that the deprotonation of a site at
      pH values above 9 restricts reorientational motion. This suggests that
      reorientations in M may be correlated with proton release.

PMID- 9172760
TI  - Reversal of the surface charge asymmetry in purple membrane due to single amino
      acid substitutions.
AB  - Twenty-seven mutant bacteriorhodopsin's were screened to determine the PKa for
      reversal of the permanent electric dipole moment. The photoelectric response of
      an aqueous purple-membrane suspension was used to determine the direction of the
      purple-membrane dipole moment as a function of pH. The pK(a) for the dipole
      reversal of wild-type bacteriorhodopsin is 4.5. Six of the 27 mutant
      bacteriorhodopsin's were found to have a pK(a) for dipole reversal larger than
      that of wild-type bacteriorhodopsin. Two of these mutants, L93T and L93W, involve
      a neutral amino acid substitution in the interior of the protein. The direction
      of the purple-membrane permanent electric dipole moment is determined by the
      purple-membrane surface charge asymmetry. We conclude that these two
      substitutions, which do not involve charge replacement, alter the pK(a) for the
      reversal of the purple-membrane surface charge asymmetry. We suggest that these
      changes to the pK(a) are due to altered protein folding at the surface of the
      purple-membrane induced by single-site substitutions in the protein interior.

PMID- 9172761
TI  - The residues Leu 93 and Asp 96 act independently in the bacteriorhodopsin
      photocycle: studies with the leu 93-->Ala, Asp 96-->Asn double mutant.
AB  - Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation
      of the Schiff's base is the rate-limiting step in the photocycle of the D96N
      mutant, whereas retinal re-isomerization and return of the protein to the initial
      state constitute the rate-limiting events in the photocycle of the L93A mutant.
      Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than
      100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down
      by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M
      intermediate, as well as the formation and decay of the O intermediate, are
      slowed down dramatically. The photocycle is completed by the decay of a long
      lived O intermediate, as in the L93A mutant. The decay of the M and O
      intermediates in the double mutant parallels the behavior seen in the single
      mutants over a wide temperature and pH range, arguing that the observed
      independence is an intrinsic property of the mutant. The slow decay of the M and
      O intermediates can be selectively and independently reversed under conditions
      identical to those used for the corresponding intermediates in the D96N and L93A
      single mutants. Because the effects of the two individual mutations are preserved
      in the double mutant and can be independently reversed, we conclude that residues
      Asp 96 and Leu 93 act independently and at different stages of the
      bacteriorhodopsin photocycle. These results also show that formation of the O
      intermediate only requires protonation of the Schiff's base and is independent of
      the protonation of Asp 96 from the aqueous medium.

PMID- 9172762
TI  - Energy migration in the light-harvesting antenna of the photosynthetic bacterium
      Rhodospirillum rubrum studied by time-resolved excitation annihilation at 77 K.
AB  - The intensity dependence of picosecond kinetics in the light-harvesting antenna
      of the photosynthetic bacterium Rhodospirillum rubrum is studied at 77 K. By
      changing either the average excitation intensity or the pulse intensity we have
      been able to discriminate singlet-singlet and singlet-triplet annihilation. It is
      shown that the kinetics of both annihilation types are well characterized by the
      concept of percolative excitation dynamics leading to the time-dependent
      annihilation rates. The time dependence of these two types of annihilation rates
      is qualitatively different, whereas the dependencies can be related through the
      same adjustable parameter-a spectral dimension of fractal-like structures. The
      theoretical dependencies give a good fit to the experimental kinetics if the
      spectral dimension is equal to 1.5 and the overall singlet-singlet annihilation
      rate is close to the value obtained at room temperature. The percolative transfer
      is a consequence of spectral inhomogeneous broadening. The effect is more
      pronounced at lower temperatures because of the narrowing of homogeneous spectra.

PMID- 9172763
TI  - Directly probing rapid membrane protein dynamics with an atomic force microscope:
      a study of light-induced conformational alterations in bacteriorhodopsin.
AB  - This paper demonstrates that an atomic force microscope can be used to directly
      monitor rapid membrane protein dynamics. For this demonstration the membrane
      bound proton pump, bacteriorhodopsin, has been investigated. It has been
      unequivocally shown that the light-induced dynamic alterations that have been
      observed do not arise from external artifacts such as heating of the sample by
      the incident light, but that these changes can be directly linked to the light
      induced protein conformational alterations in this membrane. In essence, it has
      been shown that the light energy absorbed by bacteriorhodopsin is converted not
      only to chemical energy but also to mechanical energy. In summary a new
      ultrasensitive tool is described for monitoring the molecular dynamics of
      materials with wide applicability to fundamental and applied science.

PMID- 9172764
TI  - Correlation between surfactant/micelle structure and the stability of
      bacteriorhodopsin in solution.
AB  - The rate of solubilization and isothermal bleaching of bacteriorhodopsin (bR) in
      a series of nine alkylammonium surfactants is studied by using time-resolved
      optical spectroscopy. The surfactant series RN(+)R'(3) covers a range in tail
      length (R = C(12)H(25), C(14)H(29), or C(16)H(33)) and headgroup size and
      hydrophobicity (R' = CH(3); C(2)H(5), or C(3)H(7)). The rate of bleaching
      increases initially with increasing surfactant concentration but decreases at
      higher concentrations. Possible explanations for this behavior are discussed. The
      kinetic data are consistent with the penetration of the surfactant into the
      protein interior. Interaction of the surfactants with the protein is a
      complicated, multistep process, and the rate curves are a function of at least
      four variables: 1) the micellar environment, 2) the length of the surfactant
      tail, 3) the size of the headgroup, and 4) the hydrophobicity of the headgroup.
      Our data provide new insights into the molecular characteristics that help define
      the performance of surfactants in the solubilization and denaturation of membrane
      bound proteins.

PMID- 9172765
TI  - Nuclear magnetic resonance study of the conformation and dynamics of beta-casein
      at the oil/water interface in emulsions.
AB  - A (13)C and (31)P nuclear magnetic resonance (NMR) study has been carried out on
      beta-casein adsorbed at the interface of a tetradecane/water emulsion. (13)C NMR
      spectra show signals from the carbonyl, carboxyl, aromatic, and C alpha carbons
      in beta-casein, well resolved from solvent resonances. Only a small fraction of
      all carbon atoms in beta-casein contribute to detectable signals; intensity
      measurements show that the observable spectrum is derived from about 30 to 40
      amino acid residues.(31)P NMR spectra show signals from the five phosphoserines
      on the hydrophilic N-terminal part of the protein. Analysis of T(1) relaxation
      times of these nuclei, using the model free approach for the spectral density
      function and the line shape of the alpha-carbon region, indicates that a large
      part of the protein is in a random coil conformation with restricted motion and a
      relatively long internal correlation time. The NMR results show that the
      conformation and dynamics of the N-terminal part of beta-casein are not strongly
      altered at the oil/water interface, as compared to beta-casein in micelle-like
      aggregates in aqueous solution.

PMID- 9172766
TI  - A scanning calorimetric study of unfolding equilibria in homodimeric chicken
      gizzard tropomyosins.
AB  - Using both circular dichroism (CD) and differential scanning calorimetry (DSC),
      several laboratories find that the thermal unfolding transitions of alpha alpha
      and beta beta homodimeric coiled coils of rabbit tropomyosin are multistate and
      display an overall unfolding enthalpy of near 300 kcal (mol dimer)(-1). In
      contrast, an extant CD study of beta beta and gamma gamma species of chicken
      gizzard tropomyosin concludes that their unfolding transitions are simple two
      state transitions, with much smaller overall enthalpies (98 kcal mol(-1) for beta
      beta and 162 kcal mol(-1) for gamma gamma). However, these smaller enthalpies
      have been questioned, because they imply a concentration dependence of the
      melting temperatures that is far larger than observed by CD. We report here DSC
      studies of the unfolding of both beta beta and gamma gamma chicken gizzard
      homodimers. The results show that these transitions are very similar to those in
      rabbit tropomyosins in that 1) the overall unfolding enthalpy is near 300 kcal
      mol(-1); 2) the overall delta C(rho) values are significantly positive; 3) the
      various transitions are multistate, requiring at least two and as many as four
      domains to fit the DSC data. DSC studies are also reported on these homodimeric
      species of chicken gizzard tropomyosin with a single interchain disulfide cross
      link. These results are also generally similar to those for the correspondingly
      cross-linked rabbit tropomyosins.

PMID- 9172768
TI  - Protein tracking and detection of protein motion using atomic force microscopy.
AB  - Height fluctuations over three different proteins, immunoglobulin G, urease, and
      microtubules, have been measured using an atomic force microscope (AFM) operating
      in fluid tapping mode. This was achieved by using a protein-tracking system,
      where the AFM tip was periodically repositioned above a single protein molecule
      (or structure) as thermal drifting occurred. Height (z-piezo signal) data were
      taken in 1 - or 2-s time slices with the tip over the molecule and compared to
      data taken on the support. The measured fluctuations were consistently higher
      when the tip was positioned over the protein, as opposed to the support the
      protein was adsorbed on. Similar measurements over patches of an amphiphile,
      where the noise was identical to that on the support, suggest that the noise
      increase is due to some intrinsic property of proteins and is not a result of
      different tip-sample interactions over soft samples. The orientation of the
      adsorbed proteins in these preliminary studies was not known; thus it was not
      possible to make correlations between the observed motion and specific protein
      structure or protein function beyond noting that the observed height fluctuations
      were greater for an antibody (anti-bovine IgG) and an enzyme (urease) than for
      microtubules.

PMID- 9172767
TI  - Structural intermediates in the assembly of taxoid-induced microtubules and GDP
      tubulin double rings: time-resolved X-ray scattering.
AB  - We have studied the self-association reactions of purified GDP-liganded tubulin
      into double rings and taxoid-induced microtubules, employing synchrotron time
      resolved x-ray solution scattering. The experimental scattering profiles have
      been interpreted by reference to the known scattering profiles to 3 nm resolution
      and to the low-resolution structures of the tubulin dimer, tubulin double rings,
      and microtubules, and by comparison with oligomer models and model mixtures. The
      time courses of the scattering bands corresponding to the different structural
      features were monitored during the assembly reactions under varying biochemical
      conditions. GDP-tubulin essentially stays as a dimer at low Mg(2+) ion activity,
      in either the absence or presence of taxoid. Upon addition of the divalent
      cations, it associates into either double-ring aggregates or taxoid-induced
      microtubules by different pathways. Both processes have the formation of small
      linear (short protofilament-like) tubulin oligomers in common. Tubulin double
      ring aggregate formation, which is shown by x-ray scattering to be favored in the
      GDP- versus the GTP-liganded protein, can actually block microtubule assembly.
      The tubulin self-association leading to double rings, as determined by
      sedimentation velocity, is endothermic. The formation of the double-ring
      aggregates from oligomers, which involves additional intermolecular contacts, is
      exothermic, as shown by x-ray and light scattering. Microtubule assembly can be
      initiated from GDP-tubulin dimers or oligomers. Under fast polymerization
      conditions, after a short lag time, open taxoid-induced microtubular sheets have
      been clearly detected (monitored by the central scattering and the maximum
      corresponding to the J(n) Bessel function), which slowly close into microtubules
      (monitored by the appearance of their characteristic J(0), J(3), and J (n) - (3)
      Bessel function maxima). This provides direct evidence for the bidimensional
      assembly of taxoid-induced microtubule polymers in solution and argues against
      helical growth. The rate of microtubule formation was increased by the same
      factors known to enhance taxoid-induced microtubule stability. The results
      suggest that taxoids induce the accretion of the existing Mg(2+)-induced GDP
      tubulin oligomers, thus forming small bidimensional polymers that are necessary
      to nucleate the microtubular sheets, possibly by binding to or modifying the
      lateral interaction sites between tubulin dimers.

PMID- 9172769
TI  - Direct observation of protein secondary structure in gas vesicles by atomic force
      microscopy.
AB  - The protein that forms the gas vesicle in the cyanobacterium Anabaena flos-aquae
      has been imaged by atomic force microscopy (AFM) under liquid at room
      temperature. The protein constitutes "ribs" which, stacked together, form the
      hollow cylindrical tube and conical end caps of the gas vesicle. By operating the
      microscope in deflection mode, it has been possible to achieve sub-nanometer
      resolution of the rib structure. The lateral spacing of the ribs was found to be
      4.6 +/- 0.1 nm. At higher resolution the ribs are observed to consist of pairs of
      lines at an angle of approximately 55 degrees to the rib axis, with a repeat
      distance between each line of 0.57 +/- 0.05 nm along the rib axis. These observed
      dimensions and periodicities are consistent with those determined from previous x
      ray diffraction studies, indicating that the protein is arranged in beta-chains
      crossing the rib at an angle of 55 degrees to the rib axis. The AFM results
      confirm the x-ray data and represent the first direct images of a beta-sheet
      protein secondary structure using this technique. The orientation of the GvpA
      protein component of the structure and the extent of this protein across the ribs
      have been established for the first time.

PMID- 9172770
TI  - Specific antigen/antibody interactions measured by force microscopy.
AB  - Molecular recognition between biotinylated bovine serum albumin and polyclonal,
      biotin-directed IG antibodies has been measured directly under various buffer
      conditions using an atomic force microscope (AFM). It was found that even highly
      structured molecules such as IgG antibodies preserve their specific affinity to
      their antigens when probed with an AFM in the force mode. We could measure the
      rupture force between individual antibody-antigen complexes. The potential and
      limitations of this new approach for the measurement of individual
      antigen/antibody interactions and some possible applications are discussed.

PMID- 9172771
TI  - Solubility of sickle hemoglobin measured by a kinetic micromethod.
AB  - We have developed a photolytic method to determine the concentration of reactive
      hemes in a solution in the presence of a trace amount of CO. By measurement of
      the bimolecular rate of CO binding, and by calibration of the rate constant under
      equivalent conditions, the concentration of the reactive hemes can be determined.
      In a solution of sickle hemoglobin, the molecules in the gel contribute
      negligibly to the recombination rate, allowing the concentration of the molecules
      in the solution phase to be determined. To optimize signal to noise, modulated
      excitation methods were employed, although the method could also be used with
      pulse techniques and suitable signal averaging. Because the optical method
      employs a microspectrophotometer, only a few microliters of concentrated Hb
      solution is required to reproduce the entire temperature dependence of the
      solubility previously determined by centrifugation using milliliter quantities of
      solutions of the same concentration. This should be especially useful for studies
      of site-directed mutants, and we present results obtained on one such HbS in
      which Leu 88 beta has been replaced by Ala. The free energy difference in the
      polymerization of the Leu 88 beta double mutant is consistent with known
      differences in the amino acid hydrophobicities. The calibration required for
      these experiments also provides an excellent determination of the activation
      energy for binding the first CO to deoxy Hb.

PMID- 9172772
TI  - Response of cardiac myocytes to a ramp increase of diacylglycerol generated by
      photolysis of a novel caged diacylglycerol.
AB  - To test the responsiveness of living cells to the intracellular messenger
      diacylglycerol, we developed a prototype caged diacylglycerol compound, 3-O
      (alpha-carboxyl-2,4-dinitrobenzyl)-1 ,2-dioctanoyl-rac-glycerol (designated alpha
      carboxyl caged diC(8)), that produces dioctanoylglycerol (diC(8)) on photolysis.
      Alpha-Carboxyl caged diC(8) is biologically inert toward diacylglycerol kinase
      and protein kinase C in vitro and is readily incorporated into cardiac myocyte
      membranes, where it has no effect before irradiation. Exposure to near-UV light
      releases biologically active diC8 in good yield (quantum efficiency = 0.2). Here
      we examine a cellular response to controlled elevation of diC8 within single
      cardiac myocytes. Twitch amplitude was monitored in electrically stimulated
      myocytes, and a ramp increase in the concentration of diC(8) was generated by
      continuous irradiation of cells loaded with the caged compound. The myocyte
      response was biphasic with a positive inotropic phase (39% increase in twitch
      amplitude), followed by a large negative inotropic phase (>80% decrease). The
      time to peak inotropy for both phases depended on the light intensity, decreasing
      from 376 +/- 51 S to 44 +/- 5 s (positive phase) and 422 +/- 118 S to 51 +/- 9 S
      (negative phase) as the light intensity was increased eightfold. Both phases were
      inhibited by the protein kinase C inhibitor chelethyrine chloride. An increase in
      extracellular K+ from 5 mM to 20 mM to partially depolarize the cell membrane
      eliminated the positive inotropic phase, but the negative inotropic response was
      largely unaltered. The results reveal new features in the response of cardiac
      muscle to diacylglycerol, including a positive inotropic phase and a complex
      responsiveness to a simple linear increase in diacylglycerol. The effects of
      photoreleased diC(8) were similar to the effects of opiate agonists selective for
      kappa receptors, consistent with a major role for diacylglycerol in these
      responses.

PMID- 9172774
TI  - Refolding, purification, and characterization of human erythropoietin binding
      protein produced in Escherichia coli.
AB  - The extracellular domain of the human erythropoietin receptor (EPO binding
      protein (EBP)) has been expressed and overproduced in Escherichia coli.
      Regardless of the presence ofpelB or ompT signal sequences the recombinant
      protein produced in this fashion appears, as with many other recombinant
      eukaryotic proteins produced in E. coli as an insoluble product in laboratory
      scale fermentations. The induction product of the pelB protein expression system
      appears as two protein forms with slightly different molecular weights. Based on
      N-terminal sequence analysis of recovered protein, these forms represent two
      variants, one with the signal sequence properly processed to yield the expected
      "native" amino terminus and another which retains the signal sequence. Both forms
      appear as insoluble fermentation products. Control of oxygen levels and pH during
      high density fermentation allows the production of only the protein variant with
      the native amino terminus. Methods reported here permit the efficient recovery of
      purified EBP which quantitatively binds EPO in solution as determined by high
      performance size exclusion chromatography. A long-lived refolding intermediate
      was observed which penultimately collapses into an active conformation. The
      active purified protein competes with membrane associated EPO receptor for
      binding [125I]EPO and neutralizes EPO-dependent stimulation in a cell based
      proliferation assay. Further, the radioligand equilibrium binding constant for
      this interaction has been determined by immobilizing EBP on agarose gel via a
      free cysteine. The production of EBP by these methods should facilitate the
      structural determination of the protein by NMR or crystallography and may serve
      as a guide for the refolding of other hematopoietic receptors.

PMID- 9172773
TI  - Expression and characterization of the human erythrocyte anion exchanger in a
      baculovirus/Sf-9 cell system.
AB  - The human erythrocyte anion-exchange protein (HAE1) has been expressed in insect
      Sf-9 cells using a recombinant baculovirus. We subcloned the full-length cDNA
      encoding HAE1 into the baculovirus expression vector pVL1392 and cotransfected Sf
      9 cells with the recombinant vector and wild-type AcMNPV DNA to obtain
      recombinant baculovirus. The expressed protein was targeted to the Sf-9 plasma
      membrane at an apparent density of approximately 0.5 x 10(6) copies/cell as
      determined by quantitative autoradiography using an HAE1-specific monoclonal
      antibody. Unlike native HAE1, the expressed protein was not glycosylated.
      Transport studies with HAE1-recombinant-infected Sf-9 cells showed saturable
      [Km(Cl-) = 44 mM; Vmax(Cl-) = 48 mEq/liter of cell waters min] and H2DIDS
      inhibitable (K(O.5) = 34 microM) 36Cl- uptake that was not present in uninfected
      cells. We also found that extracellular SO4(2-) reduced 36Cl- influx
      [K(0.5)((SO4)2-) = 26 mM], presumably through substrate competition as in
      erythrocytes. Finally, we observed that H2DIDS-inhibitable 36Cl- efflux was
      reduced by 77% in the nominal absence of a suitable counter-anion in the external
      solution (HCO3(-)-free, all-glucuronate medium), thereby providing strong
      evidence for an obligatory exchange mechanism. We conclude that there is high
      level expression of + ++HAE1 functional activity in recombinant baculovirus
      infected Sf-9 cells and that this system will prove useful for kinetic and
      structural analyses of the HAE1 protein.

PMID- 9172775
TI  - Purification and partial molecular characterization of GRP94, an ER resident
      chaperone.
AB  - GRP94 is a resident glycoprotein of the endoplasmic reticulum (ER) and a member
      of the hsp90 family of molecular chaperones. Current experimental evidence
      indicates that GRP94 functions in an as yet undefined manner in protein folding
      and assembly in the ER. We report a rapid, high-yield GRP94 purification
      procedure that yields milligram quantities of homogeneous protein suitable for
      structural and biochemical analyses. Beginning with a rough microsome fraction
      derived from porcine pancreas, GRP94 was isolated by partial detergent
      extraction, anion exchange, and gel filtration chromatography. With this
      procedure, approximately 3 mg of homogeneous GRP94 can be prepared from a 25-g
      pancreas. Heterogeneity in the migration of purified GRP94 on native and
      denaturing PAGE was observed and demonstrated to reflect variability in the N
      linked glycosylation state of the protein. Analysis by native and two-dimensional
      nonreducing/reducing gels indicated that the protein exists as a dimer of
      noncovalently associated subunits. The membrane localization of GRP94 in isolated
      pancreatic microsomes was assessed by alkali and detergent extraction. By
      comparison with the resident ER integral membrane protein TRAPalpha, GRP94 exists
      as a soluble, lumenal protein.

PMID- 9172776
TI  - Expression, purification and characterization of focal adhesion kinase using a
      baculovirus system.
AB  - Focal adhesion kinase (FAK) has been overexpressed in insect cells using a
      baculovirus expression system. A recombinant baculovirus was generated which
      contains the mouse FAK cDNA cloned into a histidine tag transfer vector.
      Synthesis of the immunoreactive recombinant protein (baculovirus focal adhesion
      kinase (BFAK) Mr approximately 125,000) in infected Sf9 cells was detected 23 h
      postinfection, with maximal accumulation occurring at 48 h postinfection. BFAK
      constituted 5.4% of total soluble protein in the insect cell lysate and
      represented 19 mg/liter culture (approximately 2 x 10(9) cells). The enzyme was
      active as a protein tyrosine kinase in both SF9 cells and in vitro. Purification
      to near homogeneity was achieved by nickel chelation chromatography. A yield of 5
      mg of purified active BFAK was consistently produced from 1 liter of infected
      insect cells. BFAK tyrosine kinase activity was characterized physically using
      poly(Glu-Tyr) as a substrate. BFAK activity required the presence of a divalent
      cation and exhibited a preference for Mn2+ over Mg2+. Maximal tyrosine kinase
      activity was attained at pH 7.2. Steady-state kinetic analysis with respect to
      ATP concentration did not conform to simple Michaelis-Menten kinetics and
      exhibited a Hill coefficient of much less than 1. Km values for ATP using native
      and autophosphorylated BFAK were 6.7 +/- 1.0 and 4.3 +/- 0.2 microM,
      respectively. Kcat values were 13.9 +/- 1.9 and 8.9 +/- 0.3 nmol/min/mg BFAK.
      Steady-state kinetics with respect to the peptide substrate did fit the Michaelis
      Menten equation and exhibited a Km value of 2.4 +/- 0.3 micro/ml.

PMID- 9172777
TI  - Bacterial expression of the Saccharomyces cerevisiae ubiquitin-conjugating enzyme
      Ubc7.
AB  - The coding sequence for the yeast ubiquitin-conjugating enzyme Ubc7 was obtained
      by PCR from Saccharomyces cerevisiae genomic DNA. This sequence was placed in a
      plasmid containing the lambdaPL promoter and was used for temperature-regulated
      expression in Escherichia coli. The expressed 18-kDa protein was isolated in the
      inclusion body fraction from bacterial lysates, in contrast to the soluble nature
      of other yeast ubiquitin-conjugating enzymes expressed in E. coli. Selective
      solubilization of the protein using 5 M urea followed by dialysis, MonoQ FPLC,
      and Superdex-75 FPLC yielded electrophoretically pure Ubc7 protein. The purified
      protein was enzymatically active as determined by formation of enzyme-linked
      thiolester with ubiquitin. The ability of Ubc7 protein to regain enzymatic
      activity after urea denaturation appears to be attributable to the stable core
      alpha/beta folded structure common to the ubiquitin-conjugating enzymes whose
      structures have been determined to date.

PMID- 9172778
TI  - Expression purification and characterization of recombinant human inducible
      prostaglandin G/H synthase from baculovirus-infected insect cells.
AB  - The inducible isoform of human prostaglandin G/H synthase (human cyclooxygenase;
      hCOX2) has been produced in Sf21 insect cells using the baculovirus expression
      system. The full-length gene for hCOX2 was placed under the control of the hybrid
      pCap/PolH promoter and recombinant virus generated by homologous recombination.
      Insect cells infected with recombinant virus synthesized active hCOX2 at levels
      exceeding 5% of total cellular protein 72 h postinfection. Optimal production on
      a preparative scale and high activity yields were attained in 8-liter spinner
      flasks using a supplemented Grace's medium containing 10% FCS. The apo-enzyme was
      purified to homogeneity by detergent extraction and ion exchange chromatography
      and functionally reconstituted with heme to form the holo-enzyme. The purified
      enzyme from insect cells was identified as hCOX2 by enzymatic activity, Western
      immunoassay, and N-terminal sequence analysis; the latter also indicated correct
      processing of the hCOX2 signal sequence. Insect recombinant hCOX2 displays high
      specific activity for both cyclooxygenase and peroxidase activities at levels
      indistinguishable from mammalian derived enzyme. Spectroscopic analysis suggests
      that the recombinant enzyme adopts native-like secondary and tertiary structure.
      The data presented here demonstrate that this system is capable of providing high
      yields of active enzyme for biochemical, biophysical, and pharmacological
      investigations.

PMID- 9172780
TI  - Expression and purification of anthrax toxin protective antigen from Escherichia
      coli.
AB  - Anthrax toxin consists of three separate proteins, protective antigen (PA),
      lethal factor (LF), and edema factor (EF). PA binds to the receptor on mammalian
      cells and facilitates translocation of EF or LF into the cytosol. PA is the
      primary component of several anthrax vaccines. In this study we expressed and
      purified PA from Escherichia coli. The purification of PA from E. coli was
      possible after transporting the protein into the periplasmic space using the
      outer membrane protein A signal sequence. The purification involved sequential
      chromatography through hydroxyapatite, DEAE Sepharose CL-4B, followed by Sephadex
      G-100. The typical yield of purified PA from this procedure was 500 microg/liter.
      PA expressed and purified from E. coli was similar to the PA purified from
      Bacillus anthracis in its ability to lyse a macrophage cell line (J774A.1). The
      present results suggest that a signal sequence is required for the efficient
      translocation of PA into E. coli periplasmic space.

PMID- 9172779
TI  - Single-step purification of recombinant wild-type and mutant HIV-1 reverse
      transcriptase.
AB  - We have devised a single-step method that enables purification of HIV-1
      recombinant reverse transcriptase directly from bacterial lysates in less than 2
      h. Clarified lysates are applied to commercial Q- and S-matrix cartridge columns
      connected in series. The columns are washed with low-salt buffer to remove
      unbound protein, then the Q column is removed and reverse transcriptase is eluted
      from the S column using a salt gradient. The purification has been carried out
      with both medium-pressure and high-pressure chromatographic systems.
      Purifications are carried out at room temperature near neutral pH, providing
      enzyme with high DNA polymerase specific activity. A crucial aspect of the
      procedure is the use of Tris buffer, a buffer that is normally incompatible in
      cation-exchange methods. The method is applicable for the purification of the
      p51/p66 heterodimer and the p5l and p66 homodimer forms of reverse transcriptase.
      We have used this method to purify wild-type reverse transcriptase and several
      recombinant proteins containing mutations correlated with dideoxynucleoside drug
      resistance.

PMID- 9172781
TI  - Separation of human serum transferrin isoforms by high-performance pellicular
      anion-exchange chromatography.
AB  - Glycoproteins are microheterogeneous with respect to their attached
      oligosaccharides. When these oligosaccharides contain sialic acid, the
      oligosaccharide microheterogeneity will impart charge heterogeneity to the
      glycoprotein. We found that two commercial preparations of human serum
      transferrin (HST), a sialylated glycoprotein, have very different chromatographic
      profiles when the samples are separated by pellicular anion-exchange
      chromatography. Each anion-exchange profile contained multiple peaks, which
      suggested that both glycoproteins have charge heterogeneity. High-pH anion
      exchange chromatography with pulsed amperometric detection (HPAEC/PAD) analysis
      of sialic acids and oligosaccharides released from the two preparations of HST
      revealed that the two preparations differed in sialic acid and sialylated
      oligosaccharide content. When oligosaccharides were released from the anion
      exchange fractions of the two HST preparations, the HPAEC/PAD oligosaccharide
      profiles showed that protein retention was directly related to sialylated
      oligosaccharide content (i.e., the longer a fraction was retained, the greater
      its sialylated oligosaccharide content). Therefore, the anion-exchange profiles
      of the two HST preparations are related to their sialylated oligosaccharide
      content. We believe that pellicular anion-exchange chromatography can be used to
      quickly monitor gross changes in the sialylation of sialylated glycoproteins due
      to physiological state, or in the case of recombinant glycoproteins, culture
      conditions and/or purification.

PMID- 9172782
TI  - Expression in Escherichia coli of cytoplasmic portions of the cystic fibrosis
      transmembrane conductance regulator: apparent bacterial toxicity of peptides
      containing R-domain sequences.
AB  - Large peptide segments (148-479 amino acids) of the cystic fibrosis transmembrane
      conductance regulator, which are projected to represent cytoplasmic portions of
      this large membrane protein, were expressed in Escherichia coli using two T7 RNA
      polymerase vectors, pET11a and pRSET. Five of the nine peptides were readily
      expressed at high levels (15-35 mg/liter) and one at an intermediate level (10
      mg/liter), but three could not be expressed at >1.5 mg/liter regardless of
      efforts to further optimize the system. Preinduction testing of these latter
      plasmids failed to demonstrate any plasmid instability, while bacterial survival
      was drastically curtailed upon induction, beyond that observed with the other
      plasmids. Peptides containing the second half of exon 13 (residues 700-830; R
      domain) appear to be especially toxic to the expressing bacteria. Peptides
      including this hydrophilic segment may be inhibiting the bacterial permeases
      which are known to he homologous to other portions of CFTR.

PMID- 9172784
TI  - High-level expression and purification of a human "mini"-hexokinase.
AB  - Human hexokinase type I is a 100-kDa enzyme with the catalytic site located in
      the C-terminal domain. We had previously expressed this domain in Escherichia
      coli, however only a small amount of the recombinant enzyme was catalytically
      active. To overcome this problem we have now expressed the "mini"-hexokinase
      using the pET expression system. An average of 1000 U of enzyme per liter of
      culture was obtained. The recombinant enzyme was purified to homogeneity by a
      combination of ion-exchange chromatography, affinity chromatography, and dye
      ligand chromatography. The enzyme was unstable under ultrafiltration; thus, a
      multicolumn purification procedure was developed in order to avoid the
      ultrafiltration steps. The recombinant "mini"-hexokinase was found to have the
      same kinetic properties as the entire enzyme. Using the method described, the
      enzyme can be obtained in sufficient quantities for biophysical and biochemical
      investigations.

PMID- 9172783
TI  - Product purification by reversible phase transition following Escherichia coli
      expression of genes encoding up to 251 repeats of the elastomeric pentapeptide
      GVGVP.
AB  - By constructing a basic gene unit encoding (GVGVP)10, it was possible to build
      concatemer genes with as many as 25 repeats of the monomer unit encoding a
      protein-based polymer with a molecular weight of greater than 100,000 Da. This
      employed the use of terminal cloning adaptor oligonucleotides as chain
      terminators to enhance the desired polymer gene size distribution. These genes
      have been expressed in Escherichia coli and the products have been purified from
      the culture lysates using a simple centrifugation method which relies upon the
      inverse temperature transitional properties of these elastomeric protein-based
      polymers. At 4 degrees C, the polymers are soluble; on raising the temperature
      above 26 degrees C, the onset temperature (Tt) for the (GVGVP)251 inverse
      temperature transition, the polymer separates out as the more dense phase. Upon
      shifting the temperature between 4 and 37 degrees C, the recombinant elastomeric
      protein-based polymers undergo reversible phase transitions from soluble (4
      degrees C) to insoluble (37 degrees C) allowing their separation from other
      cellular components by several cycles of centrifugations at alternate
      transitional states. Additional centrifugation, at a temperature just below Tt,
      allows for dramatic lowering of endotoxin levels. Furthermore, many ways of
      varying the value of Tt, such as adding salt to lower Tt or changing the degree
      of ionization in polymers with functional side chains, can be used to achieve
      purification of more complex polymers.

PMID- 9172785
TI  - Expression and purification of recombinant human tryptase in a baculovirus
      system.
AB  - B2 is a mAb that recognizes a conformational determinant on the active form of
      native tryptase, but does not recognize native tryptase that spontaneously loses
      activity in physiologic buffer. Precursor forms of recombinant human (rh) alpha-
      and rh beta-tryptase have been expressed in a baculovirus system. In each case,
      multiple electrophoretic forms were detected in both culture media and cell
      lysates of infected insect cells by Western blots developed with the G3 mAb made
      against native human tryptase. Although only 4 of 30 amino acids in the leader
      sequences of alpha- and beta-tryptase differ, rh alpha-tryptase appeared
      predominantly in the cell lysates, rh beta-tryptase predominantly in the culture
      media. B2 recognized rh alpha-tryptase and rh beta-tryptase found in the culture
      media of infected Sf-9 cells, but not that in cell lysates. Secreted forms of
      tryptase were purified to homogeneity by B2-immunoaffinity chromatography. From 1
      liter of culture fluid 1.5 to 3 mg of rh-tryptase could be purified. Each rh
      tryptase precursor was enzymatically inactive with synthetic substrates. Analysis
      of the N-terminal amino acid sequences of purified rh alpha- and rh beta-tryptase
      precursors (APAPVQA and APAPGQA, respectively) indicated that the initial 18
      amino acids of the 30-amino-acid leader sequence had been removed. Differential N
      glycosylation was found in both rh alpha-tryptase (one or two carbohydrate groups
      per molecule) and rh beta-tryptase (zero or one carbohydrate group per molecule).
      Thus, the baculovirus expression system is a useful tool for generation of rh
      alpha- and rh beta-tryptase precursors that exhibit a conformational epitope also
      present on natural tryptase and that are preferentially secreted into the culture
      media of infected cells.

PMID- 9172786
TI  - Purification and characterization of recombinant mouse growth hormone binding
      protein produced in the baculovirus expression system.
AB  - Sf21 insect cells were infected with recombinant baculovirus containing cDNA for
      the entire coding region of the mouse growth hormone binding protein (mGHBP).
      Recombinant (r) mGHBP was expressed at a yield of 17.3 mg/liter/3 days. The
      molecular size (Mr) of the rmGHBP was approximately 33,000 as estimated by SDS
      PAGE. Amino-terminal sequence analysis of the recombinant protein yielded two
      sequences: one identical to amino acids l- 15 and another corresponding to amino
      acids 14-21 of the GHR/GHBP. Western blot analysis revealed that this is the same
      Mr as that of one of the two major Mr forms of serum mGHBP. Deglycosylation of
      serum mGHBP and recombinant mGHBP caused a shift in the molecular size of both
      proteins to that expected after removal of all N-linked carbohydrates. Binding
      characteristics of the recombinant mGHBP to mouse growth hormone were similar to
      those for serum GHBP. Scatchard analysis showed an equilibrium association
      constant (Ka) for rmGHBP of 3.8 x 10(8) +/- 0.6 x 10(8) M(-1) (mean +/- SEM, n =
      3) and Ka of 9.2 x 10(8) +/- 2.0 x 10(8) M(-1) (mean +/- SEM, n = 3) for the
      serum mGHBP. In conclusion, this expression system should allow a production of
      relatively large quantities of mGHBP suitable for physiological studies on the
      role of this protein.

PMID- 9172787
TI  - Recombinant human renin produced in different expression systems: biochemical
      properties and 3D structure.
AB  - Human renin has been expressed in Sf9 and CHO cells using two different gene
      constructs. The first construct contained a foreign signal peptide fused directly
      to the sequence encoding mature renin, whereas the second construct harbors the
      sequence for preprorenin. Prorenin was produced in significantly higher amounts
      than the mature enzyme expressed without its propeptide in both expression
      systems. Both directly expressed mature renin and proteolytically derived active
      renin have been purified and cocrystallized with the renin inhibitor Ro 42-5892.
      The 3D structure has been solved for both versions and demonstrates identity
      despite different glycosylation and different N termini.

PMID- 9172789
TI  - ["Others talk about it...we do it". Quality assurance for graduate and continuing
      education].

PMID- 9172788
TI  - Negative effect of sequential serine codons on expression of foreign genes in
      Escherichia coli.
AB  - Herpes simplex virus encodes a 1298-residue protein designated ICP4 that
      regulates transcription of viral genes. Structural and functional analyses of
      ICP4 have been facilitated by production of portions of ICP4 in Escherichia coli.
      We previously observed that expression of most truncated forms of ICP4 in E. coli
      was relatively efficient, with the exception of portions of the ICP4 gene
      approximately between codons 160 and 220. We have now localized the portion of
      ICP4 that inhibits expression to a serine-rich region from position 176 to 199.
      Our experimental results suggest that codons within the serine-rich domain do not
      induce termination of transcription, do not alter the intrinsic stability of
      mRNA, and do not create a proteolytically sensitive site in this portion of ICP4.
      Silent mutations that alter codon usage of many of the 19 serine codons in this
      region had no effect on expression. However, we observed that the level of
      protein expression was inversely proportional to the number of serine codons in
      this region. The results are consistent with a model in which the serine-rich
      domain induces premature termination of translation. This effect is not due to
      any specific secondary structure in the mRNA or lack of sufficient seryl-tRNA
      synthetase. It remains to be determined whether premature termination can result
      from insufficient seryl-charged tRNAs. Our results suggest that foreign genes
      with more than 20 consecutive serine codons may be poorly expressed in E. coli.

PMID- 9172790
TI  - [Change in the spectrum of uterus-preserving myoma operations including endoscopy
      and dual myoma therapy].
AB  - OBJECTIVE: On the basis of the evaluation of 300 patients who underwent myoma
      surgery with the desire for uterus preservation at the Department of Obstetrics
      and Gynaecology of Heidelberg University, a management scheme including
      endoscopic techniques was developed. METHOD: Despite the patients' wish for organ
      preservation, in 12 cases (family planning complete, therapy-resistant sterility,
      no desire for a child) with an extremely large uterus (20th-24th week of
      gestation) or a degenerated, intramural myoma (a sarcoma not being excluded), a
      primary hysterectomy had to be performed. Overall, 37.9% of patients underwent
      conventional, 42% laparoscopic and 20.1% hysteroscopic surgery. Additionally, to
      objectify the role of a pretreatment with GnRH analogues (GnRHa), the following
      control parameters were examined in 128 patients with and 160 patients without
      pretreatment: rate of primary laparotomies, conversion, secondary hysterectomy,
      intraoperative bleedings, amount of distension medium and percentage of repeat
      interventions. RESULTS: No significant differences in the study parameters
      between study and control groups could be found in the patients treated by
      laparoscopy. In the hysteroscopy group, conversion rate (13.3 vs. 7%), operation
      time (35 vs. 21.9 min), rate of severe intraoperative bleeding (33.3 vs. 9.3%),
      amount of distension medium necessary (difference 2.1 litres) and rate of repeat
      interventions (40.4 vs. 16.3%) differed significantly between study and control
      groups. CONCLUSION: In the operative management, the key question is when to
      perform an invasive procedure. The second question should be which access route
      is the most convenient. The decision whether to give GnRHa pretreatment is also
      an individual one, especially in cases of a conventional or laparoscopic
      operative procedure. A preoperative GnRHa therapy is mandatory before
      hysteroscopy for submucous myoma.

PMID- 9172791
TI  - [Pathophysiologic principles and clinical effects of local drug therapy of tubal
      pregnancies].
AB  - OBJECTIVE: An empirically established serum beta human chorionic gonadotropin
      (beta-HCG) threshold level of 2,500 IU/l is considered as the limit for
      successful drug therapy. The purpose of our study was to ascertain if this
      threshold level correlates with the histopathology. Further, we evaluated the
      effects of local drug therapy on the tubal wall. METHODS: Between 1988 and 1993
      129 cases of tubal pregnancies were treated by local prostaglandin F2 alpha
      instillation. For final cure 30 patients had to undergo further surgical
      measures. Our study was based upon the histological samples which were excised
      during secondary operation. RESULTS: Below 2,500 IU/l beta-HCG, intraluminal
      growth of the trophoblast is more frequent, whereas at higher values extraluminal
      spread predominates (p = 0.0045). Cells of ectopic trophoblast proliferate
      significantly slower than those of intrauterine pregnancies. Prostaglandin F2
      alpha application selectively destroys ectopic gestational tissue and preserves
      the tubal wall. CONCLUSION: The integrity of the tubal wall with its contractile
      potential is essential for successful therapy by local instillation of
      prostaglandin F2 alpha.

PMID- 9172792
TI  - [Diagnosis and therapy of extrauterine pregnancy].
AB  - The combined use of transvaginal ultrasound and serial quantitative determination
      of the serum human chorionic gonadotropin (HCG) concentration offers an early and
      exact diagnosis of an ectopic pregnancy before the onset of clinical symptoms.
      Therefore, a large variety of invasive and noninvasive treatment options can be
      chosen. In patients without severe clinical symptoms, the trophoblast activity
      should be determined via the HCG course before invasive treatment methods are
      performed, because a considerable proportion part of the patients show
      spontaneous resolution of the ectopic pregnancy without further measures.
      Recently systemic treatment with methotrexate alone or local injection of
      different substances like prostaglandins, glucose, and methotrexate, etc. became
      an alternative to surgical therapy, i.e., endoscopic salpingotomy or
      salpingectomy. The success rates are generally lower in comparison to surgical
      therapy. Therefore, medical treatment is useful only in patients with a low
      trophoblast activity (e.g., < 2,500 mIU/ml HCG). However, in cases with low HCG
      values, observation alone frequently leads to a resolution. Corresponding to the
      data being available up to now, the postoperative pregnancy rate does not depend
      on this decision.

PMID- 9172793
TI  - [Diagnosis of Chlamydia trachomatis infections in routine ambulatory care of a
      gynecologic-obstetrical clinic: comparison of genome, antigen and cell culture
      detection methods for various indications].
AB  - OBJECTIVE: Comparison of four different assays for routine diagnosis of
      urogenital Chlamydia trachomatis infections. METHODS: Samples from 285 female
      patients were tested using each of the following tests: PCR (Amplicor Chlamydia
      trachomatis), ELFA (VIDAS Chlamydia), cell culture and direct immunofluorescence
      assay (DFA). RESULTS: C. trachomatis was detected by PCR in 13 endocervical swab
      specimens obtained from 189 female patients (6.9%). Among 13 PCR-positive
      samples, 10 tested positive by cell culture and DFA, and 8 were positive by ELFA.
      For 3 patients with pregnancy-related complications, a positive result was
      obtained by PCR only. Each of the 96 urethral swabs proved to be negative.
      CONCLUSIONS: PCR is more sensitive than cell culture, DFA and ELFA, especially in
      the context of C. trachomatis infection during pregnancy. In addition and in
      order to avoid false-negative PCR results, a careful collection of epithelial
      cells infected with C. trachomatis is imperative.

PMID- 9172794
TI  - [Effect of psychological factors in pregnancy on the development of parent-child
      relations. 2. Transition from prenatal to postnatal phase].
AB  - OBJECTIVE: In a longitudinal prospective study on 38 couples and their first
      child, we examined the influence of prenatally assessed psychological factors of
      the parents on somatic and psychic aspects of birth, the quality of the newly
      established parent-child relationship and the early development of the baby.
      METHODS: Half-standardized psychoanalytic interviews with the couple (pre- and
      postnatally conducted, video-recorded), the Giessen test for couples, an
      evaluation of the parents' birth narratives and a parent questionnaire about
      functional symptoms of the baby were used. RESULTS: We found a high continuity
      between the pre- and the postnatal measurements of the partnership and the
      emotional experiences of the parents. Somatic complications of the birth event
      were not correlated with prenatally assessed psychological factors. But there
      exists a highly significant correlation between the mental representations and
      the relationships of the parents and the emotional experiences of birth, the
      early relationship between the parents and their baby and manifestations of
      functional disorders of the newborn. CONCLUSIONS: Relevant psychological and
      psychosocial aspects should be included in the medical care of pregnant women.
      One should listen to the imaginations and expectations of the parents about the
      future parentship, including ambivalent feelings. The father should also be seen
      for psychological assessment.

PMID- 9172795
TI  - [Proliferating leiomyoma after hysteroscopic myoma resection].
AB  - A proliferative leiomyoma, which had possibly been removed only subtotally by
      hysteroscopic resection, grew postoperatively so that vaginal hysterectomy had to
      be carried out. The histology of the leiomyoma showed an increased expression of
      the proliferative marker Ki-67.

PMID- 9172796
TI  - [Fracture of a surgical needle in suture management of episiotomy].
AB  - The complication of a break of the surgical needle during the suture of an
      episiotomy and the disappearance of the fragment in the perineal tissue has not
      been dealt with in the available literature. From our own material, a frequency
      of 0.17/1000 (n = 22,374) can be calculated. For the authors, the best method of
      coping with this complication is the removal of the needle fragment under a
      portable digital imaging system with two needleholders according to Bozemann.

PMID- 9172797
TI  - [Room with a view for the "daughters of pain": 1828 was the beginning of new
      obstetrics in Erlangen].
AB  - The roots of clinical obstetrics at the University of Erlangen go back as far as
      the end of the 18th century. In 1796, Christian Friedrich Deutsch (1768-1843) was
      appointed as the first university teacher solely responsible for obstetrics. At
      the same time, he was also vehemently committed to the creation of a clinical
      institution for the purpose of training in obstetrics. For several reasons, the
      opening of a maternity home in a converted private house on the outskirts of town
      did not take place until 1828 under the leadership of Anton Bayer (1791-1832). In
      1854/55, it was possible to move into a new building situated directly next to
      the university hospital; this new building was planned by Eugen Rosshirt (1798
      1872). The increasing number of births and students as well as the introduction
      of gynecology finally led to the establishment, in 1878, of the first
      gynecological hospital in the sense understood by us today. The hospital was
      designed by Karl Schroder (1838-1887) who was the first Erlangen teacher of
      obstetrics to complete his habilitation in this field and probably has to be
      considered as the founder of the science of obstetrics at the University of
      Erlangen.

PMID- 9172798
TI  - [The triple test scenario for Styria. With data of the Styria Abnormalities
      Register].
AB  - OBJECTIVE: The aim of the study was to clarify by a cost-effectiveness analysis,
      if a triple-marker screening for trisomy 21 (triple test) should be established
      in Austria. METHODS: The published triple-test results of the last years were
      combined with the data of the Styrian Malformation Register covering the years
      1985-1992. The cost-effectiveness analysis was based on total costs of prenatal
      diagnosis, costs per fetus diagnosed as affected, the number of affected fetuses
      detected, and the number of procedure-related losses. RESULTS: If low costs are
      given priority, the triple test should be offered to women 35 years of age or
      older. If a high detection rate is given top priority, the test should be offered
      to all pregnant women. CONCLUSION: The results suggest that the present policy of
      maternal age screening in Austria should be replaced by maternal serum screening.

PMID- 9172799
TI  - Rationalizing autotransplant strategies for chronic myeloid leukemia.
AB  - The molecular genetic basis of chronic myeloid leukemia (CML) is well-defined,
      but until recently therapeutic approaches have been largely empiric. Conventional
      chemotherapy and interferon offer palliation, but only bone marrow
      transplantation provides for cure. Because the majority of CML patients are not
      candidates for allogeneic transplantation, autologous strategies have emerged as
      an alternative. Data from murine models of CML provide insights into the
      mechanisms by which autotransplant might be effective in the treatment of CML.
      Further dissection of the molecular pathways by which the BCR/ABL protein can
      induce leukemia offers the promise of a more targeted, rationally-designed
      therapy. When used for remission maintenance therapy following autologous bone
      marrow transplantation, specific inhibitors of BCR/ABL should provide for long
      term disease-free survival.

PMID- 9172800
TI  - Methotrexate pharmacology and resistance in childhood acute lymphoblastic
      leukemia.
AB  - Impressive gains have been made in the therapy of childhood acute lymphoblastic
      leukemia (ALL) in recent years such that remissions today are commonly achieved
      in up to 95% of patients and long term disease-free survival rates approach 70%.
      Methotrexate is a key component in ALL consolidation and maintenance therapies
      and is administered intrathecally in the prophylaxis and treatment of central
      nervous system leukemia. Critical determinants of methotrexate sensitivity and
      resistance (dihydrofolate reductase levels, methotrexate membrane transport,
      methotrexate polyglutamylation) previously described in cultured cells have
      recently been identified in lymphoblasts from children with ALL. Heterogenous
      expressions of increased dihydrofolate reductase or impaired methotrexate
      transport can be detected in both diagnostic and relapsed ALL specimens by flow
      cytometry with fluorescent methotrexate analogues. Lymphoblasts from children
      with ALL synthesize long chain polyglutamates and correlations have been
      established between the accumulation of methotrexate polyglutamates in ALL blasts
      and characteristic patient prognostic features. Variations in methotrexate
      polyglutamate accumulation may reflect changes in polyglutamate synthetic or
      degradative enzymes, or may be secondary to changes in methotrexate influx or
      dihydrofolate reductase levels. Other critical elements in treatment response to
      methotrexate include the dose and route of methotrexate administration, its
      catabolism to 7-hydroxymethotrexate, and the rate of methotrexate plasma
      clearance. A unique relationship exists between chromosome 21 and ALL
      leukemogenesis, and response to treatment including methotrexate. A better
      understanding of the molecular bases of methotrexate response and the development
      of methotrexate resistance in childhood ALL should facilitate further
      improvements in the effectiveness of methotrexate-based chemotherapy for this
      disease.

PMID- 9172801
TI  - Modulation of apoptosis with cytokines in B-cell chronic lymphocytic leukaemia.
AB  - In B chronic lymphocytic leukaemia (B-CLL) non-proliferating peripheral blood
      (PB) B cells have a long life span in vivo. In cultures, these cells die
      spontaneously by apoptosis. Interleukin (IL) 4 inhibits spontaneous apoptosis
      (SA) and promotes survival of B-CLL B cells in vitro. No such effect is observed
      in PB B cells from normal healthy donors. The anti-apoptotic effect of IL4 is
      independent of mitogen-induced cell activation but depends on the concentration
      of IL4. The protective effect of IL4 is specific and it is significantly reduced
      or abolished with anti-IL4 antibody. Interferon (IFN)-gamma and alpha- IFN also
      protect B-CLL B cells from apoptosis in vitro. Sera from B-CLL patients have
      increased levels of IFN-gamma when compared with sera from healthy donors. In
      addition, B-cells in B-CLL express detectable levels of IFN-gamma mRNA. Other
      cytokines, namely ILl, IL2, IL6 and IL7 do not affect SA of B-CLL B cells. By
      contrast, IL5 and antibody to apolipoprotein-1 (APO- 1) receptor increase SA
      significantly and in a dose-dependent manner. Interleukin 4 protects B-CLL B
      cells from IL5-, anti(alpha) APO-1- and steroid-induced apoptosis. The mode of
      action of the cytokines inducing apoptosis or protecting B-CLL B cells from dying
      is largely unknown. Recently the bcl-2 proto-oncogene has been associated with
      prolonged cell survival. However, the involvement of bel-2 in spontaneous,
      cytokine-induced or steroid-induced apoptosis in B-CLL has been controversial.
      Some authors have reported down-regulation of bcl-2 protein expression in B-CLL B
      cells undergoing SA or in steroid-treated cells with IL4 preventing this down
      regulation. By contrast, others observed no significant loss of bcl-2 protein
      expression in steroid-, alpha-APO-1 - and IL5-treated cells when compared with
      untreated or fresh cells. Also, no correlation between bcl-2 protein expression
      and protection with IL4 has been reported. In conclusion, in B-CLL IL4, IFN-gamma
      and alpha-IFN promote the survival of the leukaemic cells. These cytokines may
      therefore be involved in the pathogenesis of the B-CLL.

PMID- 9172802
TI  - Interactions involving cyclosporine A, interleukin-6, and Epstein-Barr virus lead
      to the promotion of B-cell lymphoproliferative disease.
AB  - Post-transplant patients undergoing prolonged Cyclosporine A (CsA)
      immunosuppressive therapy were reported to have an increased incidence of Epstein
      Barr virus (EBV)-associated lymphoproliferative disorders. EBV-infected B cells
      cultured with CsA demonstrated increased EBV B-cell out-growth as compared to
      those cultured without CsA. Peripheral blood mononuclear cells (PBMC), following
      infection with EBV and CsA treatment, demonstrated increased IL-6 activity in the
      culture supernatant. The induction of IL-6 appeared to differ within the various
      lymphocyte populations. In monocytes and B cells, IL-6 expression was
      preferentially induced by EBV, and initiated by the binding of the two major
      virion glycoproteins, gp350 and gp220, to CD21, or a CD21-like receptor.
      Expression of IL-6 in T cells appeared to be due mainly to CsA. B cells also
      expressed IL-6 following EBV exposure, but not following CsA treatment. EBY
      immortalized B-cell lines cultured with CsA exhibited both an increased number of
      cells expressing viral lytic-cycle antigens and increased amounts of lytic-cycle
      proteins. IL-6, which was induced by CsA in PBMC, was also capable of inducing
      the lytic viral cycle in several EBV-immortalized cells. When IL-6 was expressed,
      it was shown to act as an autocrine growth factor for B cells and to inhibit the
      immune system allowing for the promotion of B-cell tumors by impairing lymphokine
      activated killer cells. Thus CsA treatment, in promoting both increased numbers
      of lytic EBV B cells and expression of the EBV paracrine growth factor, IL-6,
      within the microenvironment of EBV B:T cell and EBV B:monocyte interactions, may
      lead to increased EBV B-cell immortalization and ultimately result in the
      promotion of B-cell lymphomas in immunosuppressed patients.

PMID- 9172803
TI  - Overexpression of the MDM2 oncogene in leukemia and lymphoma.
AB  - A cellular phosphoprotein that binds to and inactivates p53 has recently been
      identified as a product of the oncogene MDM2. Amplification of the MDM2 gene was
      found in more than a third of sarcomas and in a subset of malignant gliomas.
      Despite the absence of amplification, the MDM2 gene was overexpressed in some
      types of leukemias and lymphomas. Overexpression was significantly more frequent
      in the low-grade type of B-cell non-Hodgkin's lymphoma (B-NHL) than in the
      intermediate/high grade types of lymphoma and the overexpression was also
      significantly more frequent in the advanced rather than the earlier stages of B
      cell chronic lymphocytic leukemia (B-CLL) and B-NHL. This suggests that MDM2
      could play a role, via the p53 pathway, in tumorigenicity and/or in disease
      progression in some hematological malignancies. However, in the light of our
      findings that, in a few cases, both the overexpression of MDM2 and mutant-type
      p53 was seen, it is possible that MDM2 overexpression may also promote neoplastic
      growth by mechanisms other than inactivation of the p53 protein.

PMID- 9172804
TI  - The role of stromal cell heparan sulphate in regulating haemopoiesis.
AB  - Intimate contact between haemopoietic progenitor cells and elements of the bone
      marrow stroma is required for progenitor cell proliferation and differentiation.
      It is believed that the stroma provides particular niches for the development of
      haemopoietic cells of different lineages. Cytokines, stromal cell surface
      molecules and molecules of the stromal extracellular matrix all contribute to
      defining these microenvironmental niches. Data obtained using an in vitro model
      of haemopoiesis support the view that progenitor cell adhesion to stroma is
      mediated by multiple receptor-ligand interactions. The possibility of a tethering
      step, mediated by the engagement of stromal cell heparan sulphate with its
      ligands on the progenitor cells, preceding stable cell adhesion is discussed. The
      role of stromal cell heparan sulphate is likely to include cytokine presentation
      to progenitors as well as the tethering of progenitors to stroma. It is proposed
      that intracellular signals induced by progenitor cell adhesion to stroma act in
      association with cytokine induced signals to regulate progenitor cell
      proliferation and differentiation.

PMID- 9172805
TI  - CD44 and hyaluronan binding by human myeloid cells.
AB  - The CD44 cell surface molecule has been shown to be the principal cell surface
      receptor for hyaluronan (or hyaluronic acid), a glycosaminoglycan component of
      marrow extracellular matrix. However, its affinity for hyaluronan is not
      constitutive, since it depends on the cell type, the stage of differentiation and
      on activation by external stimuli including certain anti-CD44 antibodies and
      phorbol esters. Except for a few lymphoid cell lines, hematopoietic cells do not
      spontaneously bind hyaluronan and initial studies reported that, contrary to
      lymphocytes, myeloid cells could not be activated to bind hyaluronan. Because
      CD44 plays an important role in the initial phases of hematopoiesis, as shown by
      experiments using blocking anti-CD44 monoclonal antibodies, its capacity to
      mediate adhesion of primitive myeloid cells has been investigated. It was found
      that CD44 could mediate spontaneous adhesion to hyaluronan of immature myeloid
      cell lines KG1, KG1a, and TF1, which serve as a model for hematopoietic
      progenitors. However, despite expressing high amounts of CD44, no more than 15%
      of bone marrow progenitors could adhere to hyaluronan. Recent experiments have
      shown that a very important feature of CD44 is its capacity to be rapidly
      activated by certain antibodies and cytokines (GM-CSF and KL) from a low affinity
      to a high affinity state for hyaluronan. These data shed light on striking
      similarities in the functional regulation of CD44 and of the two integrin
      receptors VLA-4 (a4b1), and VLA-5 (a5b1), which are also expressed on
      hematopoietic progenitors. The relevance of these data to the regulation of
      normal hematopoiesis and mobilization of CD34+ progenitors in the view of cell
      grafting is analyzed. In addition, we show that in idiopathic myelofibrosis, the
      amount of hyaluronan is markedly increased in the extracellular matrix from the
      myeloproliferative spleen. Considering that the production of cytokines is
      enhanced in this disease, we discuss whether CD44-hyaluronan interaction may have
      a role in the pathophysiology of this myeloproliferative syndrome.

PMID- 9172807
TI  - Interleukin-2 for the treatment of advanced acute myelogenous leukemia patients
      with limited disease: updated experience with 20 cases.
AB  - Since 1988 we have treated a first group of 14 patients with recombinant
      interleukin-2 (rIL-2), which was previously published, and 6 other consecutive
      patients affected by refractory or relapsed acute myelogenous leukemia (AML) with
      >5% and < or = 30% bone marrow blasts, but not suitable for further chemotherapy.
      The rIL-2 schedule consisted of four 5-day high-dose cycles administered by
      continuous infusion with a 72-hour rest period between each cycle. Patients who
      achieved a response received a lower dose of subcutaneous rIL-2 maintenance
      treatment administered for 5 days every month. Following high-dose rIL-2, 11/20
      patients (55%) obtained a complete remission (CR). Six remain in persistent CR
      after a median follow-up time of 50 months (9, 33, 49, 51, 52, 87 months,
      respectively); the length of remission is the longest in the natural history of
      the disease for each individual patient. One patient with stable disease at the
      end of rIL-2 induction is alive and well, with a stable number of blasts in the
      bone marrow, 18 months later. These 7 patients continue maintenance treatment
      with subcutaneous rIL-2. Close clinical and laboratory monitoring reveal that
      side effects are acceptable and no toxic deaths have been recorded. This update
      confirms the feasibility and antileukemic activity of high dose rIL-2 in advanced
      AML patients with limited disease, and suggests a potential clinical role of
      prolonged rIL-2 maintenance treatment.

PMID- 9172806
TI  - Comparison of interferon tolerance after autologous bone marrow or peripheral
      blood stem cell transplants for myeloma patients who have responded to induction
      therapy.
AB  - Interferon (INF) has been incorporated as part of maintenance therapy after high
      dose treatment in order to make remissions more durable. In this study we have
      compared peripheral blood stem cell transplant (PBSCT) versus autologous bone
      marrow transplant (ABMT) with respect to INF tolerance. Thirty nine PBSCT
      patients have been compared to 37 ABMT patients for INF tolerance. This is
      followed by a comparison of 15 PBSCT patients versus 21 ABMT patients for
      engraftment details, response and survival. INF was started at a median of 61
      days in the PBSCT and 58 days in the ABMT patients (P = NS). It was well
      tolerated in both groups without a significant difference in toxicity in the two
      arms. Engraftment was more rapid in the PBSCT patients with platelet recovery
      being significantly faster. Response and survival showed a favourable trend for
      ABMT patients though statistical significance was not reached and the cost of
      PBSCT was 12% cheaper. We were thus able to conclude that PBSCT grafts were as
      durable and could tolerate INF just as well as ABMT. Engraftment was more rapid
      and the procedure of PBSCT was also cheaper. Further studies with a larger group
      of patients will be required before comments on the efficacy of treatment can be
      made.

PMID- 9172808
TI  - Are "early" and "late" T-acute lymphoblastic leukemias different diseases? A
      single center study of 34 patients.
AB  - Clinical and biological parameters were retrospectively reviewed in 34 cases of T
      lineage acute lymphoblastic leukemia (T-ALL), classified as "early" (20 cases) or
      "late" (14 cases) subgroups, according to the degree of blast cell
      differentiation, assessed by immunophenotyping. In "early" T-ALL, age, co
      expression of "immature" (CD34 and HLA-Dr) or myeloid (My+) antigens,
      proliferative activity (as evaluated by Ki67 monoclonal antibody), and expression
      of the "multidrug-resistance" (MDR) phenotype (as determined by C-219 monoclonal
      antibody) were significantly higher, while WBC count and expression of CDl0 were
      significantly lower, than in "late" T-ALL. Furthermore, although no statistically
      significant difference was found between the two groups, "late" T-ALL more
      frequently displayed a greater extramedullary tumor mass ("lymphoma-like"
      syndrome), LI FAB morphology and a normal karyotype. A single patient, with
      "late" T-ALL, also showed positivity for TCR gamma/delta chains, specific
      monoclonal antibodies. On the whole, 30 patients (88.2%) achieved complete
      remission: 16(80%) were "early" and 14(100%) "late" T-ALL. No statistical
      difference was found between the two groups with respect to disease free survival
      (42% vs 54% at six years), whereas median overall survival was significantly
      shorter in "early" T-ALL (23 months vs median not yet reached at six years for
      "late" T-ALL, p < 0.05). We conclude that "early" and "late" T-ALL show clinical
      and biological differences, that could perhaps justify differential therapeutic
      approaches.

PMID- 9172809
TI  - Features of the cytokines secreted by adult T cell leukemia (ATL) cells.
AB  - Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype
      and are thought to secrete many kinds of cytokines in vivo, complicating the
      clinical features in these patients. In an attempt to specify the cytokines
      produced by ATL cells, we measured the cytokine concentration in the culture
      supernatants of three ATL cell lines, all of which were confirmed to be true
      peripheral blood ATL cell in origin. All these cell lines showed the same
      cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha),
      TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1
      receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the
      stimulatory agents used. Such limited cytokine production may indicate the
      specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover,
      these results explain some of the unusual clinical features of ATL patients.

PMID- 9172810
TI  - Lack of CD54 expression and mutation of p53 gene relate to the prognosis of
      childhood Burkitt's lymphoma.
AB  - Expression of the intercellular adhesion molecule-1 (CD54) as well as the
      mutations of p53 gene were studied in childhood Burkitt's lymphoma (BL).
      Expression of CD54 was identified in 6 of 15 fresh BL cases. Mutations of p53
      gene, analyzed by polymerase chain reaction-single stranded chain polymorphism
      followed by sequencing, were found in 5 of 14 cases examined. Interestingly, all
      the cases with p53 mutation were CD54 negative. This high frequency of p53
      mutation in the CD54 negative group prompted us to analyze the clinical features
      of these cases. Six of 15 cases died within 21 months after initiation of therapy
      and five of these were CD54 negative. In addition, four of these had p53
      mutation. These results suggest that the lack of CD54 by BL cells may provide the
      background for the mutation of p53 gene to occur which could result in the
      transformation to a more aggressive phenotype.

PMID- 9172811
TI  - Molecular diagnosis and clinical relevance of t(9;22), t(4;11) and t(1 ;19)
      chromosome abnormalities in a consecutive group of 141 adult patients with acute
      lymphoblastic leukemia.
AB  - Over a time period of five years leukemic blast samples from 141 consecutive
      patients with adult ALL were referred to our laboratory, for molecular evaluation
      of chromosome abnormalities. The t(9;22), t(4;11) and t(1;19) which are most
      commonly found in adult ALL with a B-precursor phenotype were molecularly
      analyzed by similar RT-PCR based protocols. BCR-ABL transcripts generated by the
      t(9;22) translocation were demonstrated in 36 patients (25%) and were restricted
      to the 109 patients with B precursor ALL (33% of this group). Of 83 patients
      showing a, common phenotype (CD10+), 34 were BCR-ABL positive (41%) whereas only
      2 out of 26 with Null ALL (HLADr+, CD19+, CD10) were positive. Interestingly, the
      percent of BCR-ABL positive CD1O+ ALL increases significantly with age being 20%
      in patients less than 30 years old and more than 50% in older patients. None of
      the T-ALL (24 patients) and B-ALL (8 patients) were positive. The majority of
      cases (67%) showed the p190 gene subtype. The cytogenetic diagnosis of
      Philadelphia chromosome was always confirmed by the molecular analysis and this
      approach allowed for the detection of the presence of the BCR-ABL rearrangement
      in 26 patients when a negative result or no metaphases were obtained. The
      complete remission rate was similar among BCR-ABL positive and negative patients
      but a shorter remission duration was observed in those showing molecular evidence
      of t(9;22) and this finding was significantly evident in CD1O+ ALL patients. By
      means of comparison, in most of the same adult ALL patients, we analyzed the yet
      unrecognized prevalence of the t(4;11) and t(1;19) translocations by the
      molecular analysis of their chromosomal breakpoints. Rearrangements of the ALL-1
      gene on 11q23 band and ALL- l1AF.4 fusion transcripts specific for the t(4;11)
      were demonstrated in 7 out of the 21 Null ALL investigated, with no additional
      positive cases found among the other ALL subgroups. Overall the clinical behavior
      of t(4; 11) positive patients was dismal with a very short CR duration. Chimeric
      E2A-PBX1 transcripts generated by the t(1;19) were found in only two of the 87 B
      precursor ALL analyzed. The presented results provide further evidence for the
      utility of RT-PCR based methods for the molecular diagnosis of chromosome
      translocations in ALL. The identification of such abnormalities can significantly
      contribute to the identification of more appropriate therapeutic options for
      standard and high risk ALL patients

PMID- 9172812
TI  - Fludarabine in resistant or relapsing B-cell chronic lymphocytic leukemia: the
      Spanish Group experience.
AB  - Fludarabine produces high response rates in patients with B-cell chronic
      lymphocytic leukemia (CLL). Nevertheless, response to fludarabine of patients
      with previously treated CLL varies from 17% to 74% (0% to 38% CR). In 68 patients
      with heavily pretreated and advanced CLL, an overall response rate to fludarabine
      of 28% (4% CR) was observed. Response correlated with sensitivity of the disease
      to previous treatments (relapsing vs. refractory disease) (62% vs. 20%; p =
      0.005) and, albeit not significantly, with the number of cycles of fludarabine
      (>3 vs. < or = 3) that patients could receive (36% vs. 15%; p = NS). Responding
      patients had a longer survival (median, not reached) than those not responding
      (median, 11 months) (p = 0.03). Severe toxicity was observed in some cases. It is
      concluded that fludarabine is a highly useful agent in CLL. However, in order to
      improve its effectiveness and decrease its toxicity, fludarabine should be given
      as soon as a lack of response to front-line therapy is observed and before the
      disease becomes completely resistant to therapy.

PMID- 9172813
TI  - Mobilization of peripheral blood progenitor cells following CHOP treatment
      combined with delayed granulocyte colony-stimulating factor administration in
      patients with non-Hodgkin's lymphoma.
AB  - The kinetic change in peripheral blood progenitor cells (PBPC) during 3 to 6
      cycles of standard CHOP regimen supported with human recombinant granulocyte
      colony-stimulating factor (rG-CSF) was investigated in three patients with newly
      diagnosed intermediate grade, diffuse large cell type, non-Hodgkin's lymphoma
      (NHL) without bone marrow invasion. Patients were given rG-CSF subcutaneously (2
      mu g/kg/day) initiated when total leukocytes was < 3.0 x 10(9)/1. When the
      leukocyte count remained at >3.0 x 10(9)/1, rG-CSF was started 10 days following
      the prior CHOP. Treatment with rG-CSF was discontinued after the leukocyte count
      reached >10.0 x 10(9)/1, and CHOP was started the next day (CHOP-G regimen). The
      number of PBPC was monitored by clonal assay in patients 1-3. No severe
      leukopenia with <0.5 x 10(9)/1 of neutrophils was seen in any patient. Colony
      forming unit granulocyte-macrophage (CFU-GM) significantly increased after 2-3
      days of consecutive administration of rG-CSF. The magnitudes of maximum
      amplification of CFU-GM in patients 1, 2, and 3, were 56-fold (during 3 cycles of
      CHOP-G), 216-fold (during 2 cycles), and 67-fold (during 4 cycles), respectively,
      and the absolute numbers of the maximum CFU-GM/ml blood were 983, 7,568, 9,865,
      respectively. In one patient who was given 6 cycles of CHOP-G, the peak values of
      mobilized CFU-GM in each cycle did not substantially decrease until 6 cycles of
      CHOP-G had been completed. Thus, the CHOP-G regimen described here seems to be
      very efficient increasing the circulating CFU-GM prior to harvesting PBPC.

PMID- 9172814
TI  - Prognostic implications in myelodysplastic syndromes: A review of 62 cases.
AB  - We retrospectively reviewed 62 MDS patients (15 RA, 3 RARS, 10 CMML, 20 RAEB, 14
      RAEBT) to clarify the current problems in their management. Median survival of RA
      and RARS patients was 67.9 months and significantly longer than that of CMML,
      RAEB, or RAEB-T patients with median survivals of 16.1, 16.8, and 9.5 months,
      respectively. Karyotypic abnormalities were observed in 58% of the patients
      examined. Forty-two patients died, 16 (38%) of leukemic transformation and
      21(50%) of bone marrow failure. While most of the RAEB-T patients of all ages and
      all the RAEB patients diagnosed below 60 years of age died of transformation, 70%
      of the older RAEB patients died of infection. Prognosis after transformation was
      poor and 12 patients died within two months. These results indicate that
      management after transformation and treatment against infection in RAEB patients
      with advanced age are crucial to improve the prognosis in MDS.

PMID- 9172815
TI  - Molecular characterization of an unusual non-Hodgkin's B-lymphoma cell line
      ("Farage") lacking the ability to produce immunoglobulin polypeptide chains.
AB  - "Farage" is a cell line derived from a patient who had a diffuse and mixed type
      malignant lymphoma. In a previous study it was shown that Farage cells expressed
      B-cell markers, but not membrane IgM. Karyotypic analysis showed that in contrast
      to most follicular cell lymphomas, Farage did not have the 14;18 chromosomal
      translocation. In the present work Farage was further characterized by Southern
      and Northern blot analyses. Two rearranged heavy chain alleles and one rearranged
      kappa chain gene were detected. The cells expressed both mu and kappa mRNA, even
      though at a 3-7 fold lower level than that found in the control Daudi and DG-75
      Burkitt lymphomas. Farage cells did not express the terminal deoxynucleotydyl
      transferase gene (TdT), nor the recombination activating genes RAG-1 and RAG-2,
      known as markers of the pre-B cell stage. These results show that Farage
      represents a mature B-cell rather than a pre-B cell. Despite the presence of C
      kappa and C mu RNAs, no Ig polypeptide chains were produced by Farage as judged
      by immunoblotting and biosynthesis labeling assays. Ig mRNAs were detected on the
      polysomal fraction, but at a lower level relative to Daudi cells. Our combined
      results suggest that in Farage cells translation of Ig mRNA is not fully blocked
      at the stage of translation initiation. Farage cells may express "germline" or
      mutated variants of Ig mRNAs. The unusual phenotype of Farage may reflect a
      normal as yet unknown stage of B-cell differentiation, or it may be due to an
      aberrant expression developed after malignant transformation.

PMID- 9172816
TI  - Flow cytometric detection of CD44 (H-CAM) in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a rare clonal B-cell disorder characterized by a
      distinctive pattern of infiltration of hairy cells (HCs) in the bone marrow (BM),
      hepatic sinusoids and splenic red pulp. HCs express a wide spectrum of matrix
      binding integrins, which influence their migratory behaviour and subsequent
      tissue localization. CD44 distribution and staining intensity on HCs from the BM
      and peripheral blood (PB) were investigated using dual-color flow cytometry. HCs
      from all cases expressed CD44, but the staining intensity of the positive
      population was significantly higher than normal residual lymphocytes (p < 0.0005)
      and medullary HCs in those patients exhibiting additional hairy cell
      dissemination in the peripheral blood. It is of interest to speculate that the BM
      microenvironmental may deliver signals which down-regulate CD44 expression on
      resident HCs compared to HCs recirculating in peripheral blood. CD44 expression
      on HCs may help clarify their homing mechanisms in the bone marrow and to define
      phenotypic subsets with different clinical and pathological behaviours.

PMID- 9172817
TI  - The complement system in chronic lymphocytic leukemia: a possible role in
      autoimmune manifestations.
AB  - We describe the complement system of three CLL patients who developed autoimmune
      complications in the course of their disease. The complement profile was
      pathological in both CLL patients with active autoimmune diseases, while it
      showed no deficiency in the patient with quiescent autoimmunity. The complement
      profile could be an early marker for development of autoimmunity in CLL patients

PMID- 9172818
TI  - Multifocal plasmacytoma of hand and foot bones.
AB  - Simultaneous occurrence of localized plasmacytomas of both hands and feet has not
      been reported so far. Here we report a 40-year old female patient, who had at
      presentation pain and deformity. Of hands and feet, with numerous cystic lytic
      lesions of phalangeal, metacarpal and metatarsal bones, detected by X-rays. The
      biopsy of the affected bone showed moderately differentiated plasmacytoma of
      lambda light chain type (lambda-LC). Serum and urine biochemical analysis
      revealed the existence of lambda LC monoclonal component. The patient was treated
      by local radiotherapy and subsequent systemic chemotherapy, which consisted of 3
      cycles of the M-2 protocol and 7 cycles of melphalan-prednisone. Five years after
      the diagnosis, the absence of plasmacytoma was confirmed by puncture biopsy of
      the left hand phalanx. Monoclonal protein in serum and urine was not detected.

PMID- 9172819
TI  - A patient with Werner's syndrome and erythroleukemia: just coincidence?
AB  - Werner's syndrome is a rare clinical entity and approximately 150 cases have been
      reported in the medical literature. Werner's syndrome, inherited by autosomal
      recessive transmission, is characterized primarily by a short stature, premature
      greying and balding, trophic ulceration of the legs, diabetes mellitus and
      hypogonadism. These features combine to present a picture of adult progeria. In
      this brief report we describe a 51-year-old Bedouin male with Werner's syndrome,
      diagnosed as erythroleukemia (AML-6), and presenting as acute pancytopenia. The
      patient died two months after diagnosis. This is a rare case of erythroleukemia
      in a patient with Werner's syndrome. We survey current knowledge of the
      cytogenetic pathogenesis of Werner's syndrome and erythroleukemia, and attempt to
      explain the possible link between these two rare syndromes.

PMID- 9172820
TI  - Unusual chromosome abnormalities in primary central nervous system lymphoma.
AB  - Primary central nervous system (PCNS) lymphoma is a relatively rare disease. The
      Epstein-Barr virus (EBV) has often been implicated in the development of
      lymphomas. Few cytogenetic. studies on PCNS lymphomas have been reported. We
      describe here an unusual case of PCNS B cell lymphoma, centroblastic polymorphic
      type without coexistent immune deficiency. The cytogenetic study showed unusual
      abnormalities: t(l;9) (q25;p21); del (6) (q14 q25), trisomy 12 and in addition
      one clone with trisomy 7 and loss of chromosome X. We did not observe any
      chromosome 14 abnormality, which is more commonly reported in PCNS lymphomas.

PMID- 9172821
TI  - Limited activity of mini-dose interferon alpha-2a in the treatment of
      myelodysplastic syndrome.
AB  - Impairment in marrow function often characterizes the evolution of
      myelodysplastic syndrome. As a differentiating agent, interferon alpha 2a (INF
      alpha) has been shown to be active in the correction of cytopenias related to
      myelodysplastic syndromes (MDS). We report the clinical course of 9 patients with
      MDS treated with low-dose subcutaneous INF alpha (1 x 10(6), 3 times per week). A
      significant effect on anemia was only demonstrated in one patient (11%). In the
      other, eight, therapy was totally ineffective and four of them could not receive
      the complete treatment due to worsening cytopenias or leukemic transformation. In
      conclusion, in our study, INF alpha had only limited activity in the treatment of
      myelodysplastic syndrome.

PMID- 9172822
TI  - Hypercalcemia in a patient with chronic lymphocytic leukemia evolving into
      Richter's syndrome.
AB  - Hypercalcemia is a rare complication of chronic lymphocytic leukemia (CLL),
      mostly seen in the context of advanced disease, for which different pathogenetic
      mechanisms have been postulated. A CLL patient who developed hypercalcemia in the
      setting of Richter's syndrome is reported. She was a 69-year old woman with stage
      B (II) CLL of 28-month duration, who presented with mental confusion, anorexia,
      vomiting, and diffuse bone pain, with hypercalcemia being subsequently found. A
      lymph node biopsy demonstrated evolution of CLL into Richter's syndrome. Serum
      levels of parathyroid hormone (PTH), PTH-related peptide and several cytokines
      were normal. The hypercalcemia initially responded to conventional treatment and
      chemotherapy, but it reappeared coincidentally with disease progression and the
      development of osteolytic lesions. Richter's syndrome should be kept in mind in
      CLL patients with hypercalcemia.

PMID- 9172823
TI  - Lymphocyte infusion for delayed extramedullary relapse of acute leukemia
      following bone marrow transplantation.
AB  - We report a case of extramedullary relapse of acute myelogenous leukemia twelve
      years after allogeneic bone marrow transplantation. Due to the localized nature
      of the relapse, we were able to eliminate a majority of the tumor burden,
      utilizing local irradiation. Destined with eventual systemic leukemia relapse,
      further therapy utilizing donor lymphocytes was given at a time of minimal
      disease burden. The patient remains in a state of complete remission.

PMID- 9172824
TI  - Host-parasite dynamics and the evolution of host immunity and parasite fecundity
      strategies.
AB  - We explore evolutionarily stable co-evolution of host-macroparasite++
      interactions in a discrete-time two-species population dynamics model, in which
      the dynamics may be stable, cyclic or chaotic. The macroparasites are assumed to
      harm host individuals through decreased reproductive output. Hosts may develop
      costly immune responses to defend themselves against parasites. Parasites compete
      with conspecifics by adjusting their fecundities. Overall, the presence of both
      parasites and the immune response in hosts produces more stable dynamics and
      lower host population sizes than that observed in the absence of the parasites.
      In our evolutionary analyses, we show that maximum parasite fecundity is always
      an evolutionarily stable strategy (ESS), irrespective of the type of population
      interaction, and that maximum parasite fecundity generally induces a minimum
      parasite population size through over-exploitation of the host. Phenotypic
      polymorphisms with respect to immunity in the host species are common and
      expected in ESS host strategies: the benefits of immunication depend on the
      frequency of the immune hosts in the population. In particular, the steady-state
      proportions of immune hosts depend, in addition to all the parameters of the
      parasite dynamics only on the cost of immunity and on the virulence of parasites
      in susceptible hosts. The implicit ecological dynamics of the host-parasite
      interaction affect the proportion of immune host individuals in the population.
      Furthermore, when changes in certain population parameters cause the dynamics of
      the host-parasite interaction to move from stability to cyclicity and then to
      chaos, the proportion of immune hosts tend to decrease; however, we also detected
      counter-examples to this result. As a whole, incorporating immunological and
      genetic aspects, as well as life-history trade-offs, into host-macroparasite
      dynamics produces a rich extension to the patterns observed in the models of
      ecological interactions and epidemics, and deserves more attention than is
      currently the case.

PMID- 9172825
TI  - Matching among multiple random sequences.
AB  - In searching for strong homologies between multiple nucleic acid or protein
      sequences, researchers commonly look at fixed-length segments in common to the
      sequences. Such homologies form the foundation of segment-based algorithms for
      multiple alignment of protein sequences. The researcher uses settings of
      "unusualness of multiple matches" to calibrate the algorithms. In applications
      where a researcher has found a multiple matching word, statistical significance
      helps gauge the unusualness of the observed match. Previous approximations for
      the unusualness of multiple matches are based on large sample theory, and are
      sometimes quite inaccurate. Section 2 illustrates this inaccuracy, and provides
      accurate approximations for the probability of a common word in R out of R
      sequences. Section 3 generalizes the approximation to multiple matching in R out
      of S sequences. Section 4 describes a more complex approximation that
      incorporates exact probabilities and yields excellent accuracy; this
      approximation is useful for checking the simpler approximations over a range of
      values.

PMID- 9172826
TI  - Links between maximum likelihood and maximum parsimony under a simple model of
      site substitution.
AB  - Stochastic models of nucleotide substitution are playing an increasingly
      important role in phylogenetic reconstruction through such methods as maximum
      likelihood. Here, we examine the behaviour of a simple substitution model, and
      establish some links between the methods of maximum parsimony and maximum
      likelihood under this model.

PMID- 9172827
TI  - Conjugation-specific genes in the ciliate Euplotes crassus: gene expression from
      the old macronucleus.
AB  - Following mating or conjugation, the hypotrichous ciliate Euplotes crassus
      undergoes a massive genome reorganization process. While the nature of the
      rearrangement events has been well studied, little is known concerning proteins
      that carry out such processes. As a means of identifying such proteins,
      differential screening of a developmental cDNA library, as well as construction
      of a cDNA subtraction library, was used to isolate genes expressed only during
      sexual reproduction. Five different conjugation-specific genes have been
      identified that are maximally expressed early in conjugation, during the period
      of micronuclear meiosis, which is just prior to macronuclear development and the
      DNA rearrangement process. All five genes are retained in the mature
      macronucleus. Micronuclear, macronuclear, and cDNA clones of one gene (conZA7)
      have been sequenced, and the results indicate that the gene encodes a putative
      DNA binding protein. In addition, the presence of an internal eliminated sequence
      in the micronuclear copy of the conZA7 gene indicates that this conjugation
      specific gene is transcribed from the old macronucleus.

PMID- 9172828
TI  - Combined action of inhibitors of S-adenosylmethionine decarboxylase with an
      antimalarial drug, chloroquine, on Plasmodium falciparum.
AB  - Methylglyoxal bis (guanylhydrazone), (MGBG) a potent competitive inhibitor of S
      adenosyl-L-methionine decarboxylase activity, Berenil, a trypanocidal agent and
      chloroquine, the commonly used antimalarial resulted in a dose dependent
      inhibition of Plasmodium falciparum in vitro. The IC50 values of MGBG, Berenil
      and chloroquine were 224 microM, 40 microM and 42 nM respectively. Parasites
      treated with different concentrations of MGBG or Berenil were arrested at the
      trophozoite stage of the erythrocytic cycle. The combined action of chloroquine
      (10 nM) with either Berenil (0.1 mM) or MGBG (0.1 mM) on P. falciparum growth
      showed an additive inhibitory effect. The effect of these inhibitors alone and in
      combination on polyamine biosynthesis is also reported.

PMID- 9172829
TI  - Up-regulation of action mRNA and reorganization of the cytoskeleton in Entamoeba
      histolytica trophozoites.
AB  - Actin mRNA levels were measured in Entamoeba histolytica trophozoites after
      experimentally inducing changes in the organization of the cytoskeleton. The
      treatment of trophozoites with forskolin, N6,2'-O-dibutyryl-adenosine 3':5'
      cyclic monophosphate, and phorbol myristate acetate induced the organization of
      actin into multiple dots and defined structures with a concomitant increase in F
      actin content. Cytochalasin D elicited polarization of the structured actin and
      formation of aggregates, as well as an increment in F-actin. Simultaneously, up
      regulation of actin mRNA levels was produced by all the drugs. De novo synthesis
      of actin mRNA, as measured by nuclear run-ons, showed increased transcription of
      actin mRNA. On the other hand, treatment of cells with actinomycin D blocked the
      elevation of actin mRNA synthesis induced by forskolin, dibutyryl cyclic AMP, or
      cytochalasin D whereas, the increment induced by PMA was not affected. These data
      indicate a regulatory control of actin mRNA synthesis at the transcriptional
      level by forskolin, dibutyryl cyclic AMP and cytochalasin D, and transcriptional
      as well as post-transcriptional controls by phorbol myristate acetate. The
      experiments presented here suggest the possibility that, regulation of actin mRNA
      transcription in E. histolytica trophozoites is linked to growth conditions, that
      are accompanied by reorganization of the actin cytoskeleton and thus, related to
      the motility and invasiveness of the parasite.

PMID- 9172830
TI  - Intraspecific variation in Cryptocaryon irritans.
AB  - Intraspecific variation in the ciliate Cryptocaryon irritans was examined using
      sequences of the first internal transcribed spacer region (ITS-1) of ribosomal
      DNA (rDNA) combined with developmental and morphological characters. Amplified
      rDNA sequences consisting of 151 bases of the flanking 18 S and 5.8 S regions,
      and the entire ITS-1 region (169 or 170 bases), were determined and compared for
      16 isolates of C. irritans from Australia, Israel and the USA. There was one
      variable base between isolates in the 18 S region and 11 variable bases in the
      ITS-1 region. Despite their similar morphology, significant sequence variation
      (4.1% divergence) and developmental differences indicate that Australian C.
      irritans isolates from estuarine (Moreton Bay) and coral reef (Heron Island)
      environments are distinct. The Heron Island isolate was genetically closer to
      morphologically dissimilar isolates from Israel (1.8% divergence) and the USA
      (2.3% divergence) than it was to the Moreton Bay isolates. Three isolates
      maintained in our laboratory since February 1994 differed in sequence from
      earlier laboratory isolates (2.9% to 3.5% divergence), even though all were
      similar morphologically and originated from the same source. During this time the
      sequence of the isolates from wild fish in Moreton Bay remained unchanged. These
      genetic differences indicate the existence of a founder effect in laboratory
      populations of C. irritans. The genetic variation found here, combined with known
      morphological and developmental differences, is used to characterise four strains
      of C. irritans.

PMID- 9172831
TI  - Effects of dichloroisoproterenol on macromolecular synthesis and differentiation
      in Tetrahymena vorax.
AB  - The effect of dichloroisoproterenol on macrostomal cell formation in Tetrahymena
      vorax was examined and the drug was found to be 50% inhibitory at a concentration
      of 88 microM. Cellular uptake and incorporation of a variety of radiolabelled
      precursors was monitored in the presence of dichloroisoproterenol. The results
      demonstrate a strong, concentration-dependent inhibitory effect on RNA and
      protein biosynthesis, with a lesser inhibition observed for lipid biosynthesis.
      These data indicate that dichloroisoproterenol's reported effects on vacuole
      formation and processing in Tetrahymena are nonspecific with regard to phagocytic
      processes, but result from a general suppression of macromolecular synthesis.

PMID- 9172832
TI  - On the identity of the amoeboflagellates Didascalus thorntoni and Adelphamoeba
      galeacystis.
AB  - Didascalus thorntoni, Singh 1952 has been classified alternately as a separate
      genus or as a species of Naegleria. In the 18th edition of the American Type
      Culture Collection catalogue it is classified as Naegleria thorntoni. To resolve
      the question of its identity we have used riboprinting and sequencing of the
      small subunit ribosomal DNA. The results indicate that D. thorntoni does not
      belong to the genus Naegleria. The sequence of the small subunit ribosomal DNA
      differs only in 20 nucleotides (1%) from that of Paratetramitus jugosus. The
      difference is much smaller than between some species of Nageleria. Therefore, it
      is not clear whether D. thorntoni should be considered as a species of
      Paratetramitus or as a separate genus. The strain used in different laboratories
      as the type strain of Adelphamoeba galeacystis has been identified as a Naegleria
      strain. We believe that the type strain of A. galeacystis was mislabeled prior to
      submission to the American Type Culture Collection and to the Culture Collection
      of Algae and Protozoa. A recent isolate, which on the basis of morphology was
      identified as a strain of A. galeacystis, has the identical small subunit
      ribosomal DNA sequence as D. thorntoni. Our results prove Page was right when he
      stated that Adelphamoeba might be a synonym of Didascalus.

PMID- 9172833
TI  - Ribosomal DNA sequence of Nucleospora salmonis Hedrick, Groff and Baxa, 1991
      (Microsporea:Enterocytozoonidae): implications for phylogeny and nomenclature.
AB  - Rules of zoological nomenclature, morphological data, and ribosomal DNA sequence
      data support the validity of the genus Nucleospora, and its placement in the
      family Enterocytozoonidae. Although Nucleospora exhibits most of the
      distinguishing morphological characteristics of the family Enterocytozoonidae
      Cali and Owen, 1990, the distinctively different hosts (fish and humans,
      respectively) and sites of development (the nuclei of immature blood cells and
      the cytoplasm of enterocytes) support the placement of Nucleospora and
      Enterocytozoon into separate genera. Ribosomal DNA sequence comparisons between
      Nucleospora salmonis and Enterocytozoon bieneusi showed 19.8% genetic divergence
      in the large and small subunit regions. Although more inter- and intrageneric
      comparisons are needed before percent homology of ribosomal DNA can be used as a
      criterion for the separation of genera, the genetic divergence between the two
      species is sufficiently large to deter suppression of the genus Nucleospora as a
      junior synonym of Enterocytozoon. A polymerase chain reaction test for the
      detection of N. salmonis in chinook salmon (Oncorhynchus tshawytscha), based on
      N. salmonis-specific ribosomal DNA sequence, is described.

PMID- 9172834
TI  - Phylogeny of the rumen ciliates Entodinium, Epidinium and Polyplastron
      (Litostomatea:Entodiniomorphida) inferred from small subunit ribosomal RNA
      sequences.
AB  - There complete 18S ribosomal RNA gene sequences from the rumen ciliates,
      Entodinium caudatum (1,639 bp), Epidinium caudatum (1,638 bp), and Polyplastron
      multivesiculatum (1,640 bp) were determined and confirmed in the opposite
      direction. Trees produced using maximum parsimony and distance-matrix methods
      (least squares and neighbour-joining), with strong bootstrap support, depict the
      rumen ciliates as a monophyletic group. Entodinium caudatum is the earliest
      branching rumen ciliate. However, Entodinium simplex does not pair with En.
      caudatum, but rather with Polyplastron multivesiculatum. Signature sequences for
      these rumen ciliates reveal that the published SSrRNA gene sequence from En.
      simplex is in fact a Polyplastron species. The free-living haptorian ciliates,
      The Loxophyllum, Homalozoon and Spathidium (Subclass Haptoria), are monophyletic
      and are the sister group to the rumen ciliates. The litostomes (Class
      Litostomatea), consisting of the haptorians and the rumen ciliates, are also a
      monophyletic group.

PMID- 9172835
TI  - Ultrastructural effects of lactoferrin binding on Giardia lamblia trophozoites.
AB  - Lactoferrin and its derived N-terminal peptide may be important host defenses
      against Giardia lamblia. We showed earlier that lactoferrin and the derived
      peptides have potent giardicidal activity in vitro. Using indirect
      immunofluorescence, we now demonstrate binding of lactoferrin and the peptides to
      the live trophozoite surface. Iron strongly inhibited binding of lactoferrin, and
      decreased binding of the peptides, while certain divalent metal ions decreased
      binding of all forms by about half. Lactoferrin and the peptides caused striking
      and complex morphologic changes in the trophozoite plasmalemma, endomembranes and
      cytoskeleton, and increased the electron density of the lysosome-like peripheral
      vacuoles.

PMID- 9172837
TI  - Bioavailability of sulfamethoxypyridazine following intramuscular or subcutaneous
      administration in goats.
AB  - The pharmacokinetics of sulfamethoxypyridazine (SMP) was investigated in goats
      after a single intramuscular (im) or subcutaneous (sc) administration (100 mg/kg
      body weight). The biological half lives of SMP following im and sc administration
      were found to be 11.0 and 13.7 h, respectively. The systemic availabilities of
      the drug were calculated to be 68.6 and 58.7% following im and sc injections,
      respectively. The rapidity of absorption, almost similar availability,
      comparatively longer biological half-life and ease of administration suggest that
      the sc route of administration might be preferred over the im route. To achieve
      and maintain serum concentrations 25 micrograms/mL, a rational dosage regimen of
      SMP for goats would be 55 and 38 mg/kg body weight as the loading and maintenance
      doses, respectively, with a dosage interval of 24 h by the sc route.

PMID- 9172836
TI  - Pseudorabies virus infections in pigs. Role of viral proteins in virulence,
      pathogenesis and transmission.
AB  - This paper reviews new findings on the biological functions of pseudorabies virus
      (PRV) proteins. It focuses on the role of PRV proteins in the pathogenicity,
      immunogenicity and transmission of PRV vaccine strains in pigs. Furthermore, it
      evaluates potential risks that are connected with the use of PRV vector strains.
      Special emphasis is placed upon the spread of genetically engineered vaccine
      strains within pigs or between pigs.

PMID- 9172838
TI  - In vivo studies on lysosubtilin. I. Efficacy for prophylaxis and treatment of
      gastrointestinal disorders in newborn calves.
AB  - This is the first part of a research report on the in vivo properties of
      lysosubtilin, a broad-spectrum preparation of lytic enzymes from Bacillus
      subtilis designed for veterinary medicine. This preparation has both
      antimicrobial properties and the capacity to compensate for digestive enzyme
      deficiencies in newborn calves. This study demonstrates its efficacy for both the
      prophylaxis and treatment of calf gastrointestinal disorders. Dose determination
      studies involved calves fed with colostrum or later milk, supplemented with 10
      g/L of sodium bicarbonate, which received either a prophylactic dose of
      lysosubtilin of 2 x 10(4) U/kg of weight given twice daily for 10 days beginning
      with the first feeding (30-45 min after birth) or a therapeutic dose of 2.5 x
      10(4) U/kg of weight given twice daily until recovery. These could be used for
      the prophylaxis and treatment, respectively, of the disorders mentioned above
      with an efficacy up to 100%. Trials in veterinary medicine were carried out in
      four former Soviet Union republics. More than 16,000 newborn calves were
      involved. The efficacy of prophylaxis and treatment was found to be 94.4-100% and
      95.7-100% respectively, while the efficacy of regular methods was no higher than
      82.0 and 91.8%, respectively. A positive impact of lysosubtilin on the
      improvement of digestive tract functioning, development of an animal and its
      protective functions against disease was also demonstrated. The consequent
      increases in calves' daily weight gain, abomasal proteolytic capacity as well as
      in amount of gamma-globulin, lysozyme and bactericidal activities in their blood
      sera were significant.

PMID- 9172839
TI  - [Diagnosis of bovine fascioliasis using serology of pools of sera. Interpretation
      in field conditions].
AB  - The efficacy of a serological test (ELISA with excretory-secretory products of
      Fasciola hepatica as an antigen) for the diagnosis of bovine fascioliasis was
      assessed under field conditions using pools of sera from 170 herds. Blood samples
      were collected from six to ten heifers and from five to ten adults in each herd.
      In 92 of the herds (Group 1) the animals had not been treated for fascioliasis;
      in 78 herds (Group 2), a fasciolicide had been used 3 to 6 months earlier. In
      each herd, three serum pools were examined: aliquots from all the animals sampled
      in a herd (GM); aliquots from heifers only (PM); and aliquots from the cows only
      (PM). Individual sera and the pools (GM and PM) were analyzed similarly and the
      specific antibody titer was calculated by comparison with laboratory standards.
      The antibody titer for pooled sera were correlated with the proportion of
      positive sera in the pool (P < 0.0001); but these could not be used to estimate
      the prevalence of seropositivity in a herd. Diagnosis based on pooled sera was
      less effective for the detection of low prevalences of seropositivity in Group 2
      than in Group 1 because the antibody titer decreases after fasciolicide
      treatment. Infection was always detected using pooled sera in herds with a
      prevalence of seropositivity of more than 60% (GM) in Group 1, or with a
      prevalence of seropositivity of more than 70% in Group 2. The best method for
      herd diagnosis of fascioliasis was based on the presence of a positive test in
      either of the two PM groups. Using this method, all infected herds with a
      prevalence of seropositivity of more than 30% in Group 1, or 50% in Group 2, were
      accurately detected.

PMID- 9172840
TI  - Factors affecting the distribution of clinical mastitis among udder quarters in
      French dairy cows.
AB  - Factors related to the distribution of clinical bovine mastitis between rear and
      front quarters were studied using data from a 4 year survey of commercial dairy
      herds in western France. The study involved 844 mastitis cases affecting 597
      lactations of 500 French Friesian cows from 44 herds. Risk factor hypotheses were
      related to certain aspects of lactation, udder conformation and management
      practices. Distribution was modelled using a hierarchical logistic regression.
      Rear quarters were affected in 61.9% of cases. The only significant risk factor
      was the cow's parity; rear quarter clinical mastitis was more frequent in
      primiparous than in multiparous cows. In this retrospective study, udder
      conformation did not seem to play a significant role in mastitis distribution. No
      overdispersion parameter was observed, indicating that each mastitis case could
      be considered as an independent event.

PMID- 9172841
TI  - Species diversity in gastrointestinal nematode communities of dairy goats:
      species-area and species-climate relationships.
AB  - Gastrointestinal nematode communities (12 species) of dairy goats were studied in
      four regions located in the centre of the western part of France. These regions
      had very similar annual mean temperatures (11 to 12.5 degrees C) but had rainfall
      accumulations ranging from 600 to 1330 mm per year. Breeding management (area of
      pastures, number of goats in the flock, the age of the farm, and the size of the
      initial goat population) was investigated only in the driest region. The number
      of helminth species and Shannon diversity index were positively correlated to the
      permanent pasture area and negatively to the age of the farm. Evenness was
      negatively correlated to the age of the farm and increased with the increasing
      levels of rainfall. The results are interpreted in the following terms: i) large
      areas of permanent pasture include a large array of environments favourable to
      the development of the free-living stages of various species of nematodes; ii)
      age of the farm is unfavourable to the maintenance of all introduced species as
      the farms are helminth-isolated and infestation can only occur during the grazing
      season thus imposing the necessity of successive annual recolonization of the
      pastures; and iii) free-living stages are very susceptible to dryness and survive
      better in areas with heavy rainfall.

PMID- 9172842
TI  - Production and characterization of monoclonal antibodies against Taylorella
      equigenitalis.
AB  - Monoclonal antibodies were produced against Taylorella equigenitalis using two
      reference strains. Out of the 79 hybridoma clones shown to express antibodies to
      T equigenitalis by indirect immunofluorescence assay, 16 were selected for
      monoclonal antibody production and characterization. These clones recognized
      different field strains of T equigenitalis isolated in France. They showed no
      cross-reaction with bacterial strains with previously reported antigenic cross
      reactivity, nor did they react with other bacteria commonly found in genital
      flora. The epitopes recognized by eight of the monoclonal antibodies were
      situated in proteins of 150, 120, 52.7 and 22 kDa. These epitopes were resistant
      to the extraction denaturing conditions. These monoclonal antibodies could be
      used as reagents for specific detection of T equigenitalis.

PMID- 9172843
TI  - Reconstituted coronavirus TGEV virosomes lose the virus ability to induce porcine
      interferon-alpha production.
AB  - The transmissible gastroenteritis virus (TGEV) is a coronavirus which induces a
      strong interferon-alpha (IFN-alpha) production in vivo and in vitro. Previous
      studies have shown that the TGEV external protein M plays a major role in IFN
      alpha induction by a non-infectious virus, whereas protein S is not involved. The
      present study extended these results by showing that monoclonal antibodies (MAbs)
      directed at the external viral protein sM could not block IFN-alpha induction,
      which argues against a direct role for this protein. In the same type of blocking
      experiment, MAbs to the TGEV receptor aminopeptidase N did not inhibit IFN-alpha
      induction, which strongly indicates that viral replication or entry through the
      receptor is not needed for TGEV induction of IFN-alpha in leukocytes. In an
      attempt to isolate functional envelope proteins, TGEV virions were detergent
      solubilized and reconstituted in virosomes. Although BIAcore antigenic analysis
      revealed that the three external viral proteins were present on the virosomes,
      these proteins were unable to induce IFN-alpha in porcine leukocytes, and seemed
      to compete with the native virus for IFN-alpha induction. These data indicated
      that IFN-alpha inducing interactions between TGEV external proteins and
      leukocytes required a complex native envelope protein structure which has been
      lost in the virosomes.

PMID- 9172844
TI  - Brucella abortus siderophore 2,3-dihydroxybenzoic acid protects brucellae from
      killing by macrophages.
AB  - Addition of 2,3-dihydroxybenzoic acid, a siderophore produced by Brucella
      abortus, to macrophage cultures prevented intracellular killing of brucellae
      during the first 12 h after infection and increased the number of intracellular
      brucellae recovered at 48 h after infection. The protective effect could be
      demonstrated with inflammatory macrophages, interferon-gamma-activated
      macrophages and with macrophages supplemented with iron, shown elsewhere to
      facilitate killing of B abortus.

PMID- 9172845
TI  - Development of microscopic lesions in splenic cords of pigs infected with African
      swine fever virus.
AB  - Acute forms of African swine fever are characterized by hemorrhagic lesions in
      the lymphoid organs. This paper reports the evolution of lesions in the splenic
      cords of pigs inoculated with African swine fever (ASF) virus (strain Malawi'83).
      Ultrastructural examination of the splenic cords of the infected pigs revealed
      numerous macrophages attached to the muscle cells harboring virus replication
      center and cytopathic effects at 3 dpi (days post-infection). From 5 dpi, the
      splenic cords contained a large number of erythrocytes associated with abundant
      fibrin deposits, mainly arranged around the muscle cells, from which macrophages
      had disappeared. It is likely that the ASF virus replication, and consequent
      cytopathic effects, observed in the fixed macrophages of splenic cords, may be
      responsible for the fibrin deposition.

PMID- 9172846
TI  - [Differences in auditory frequency discrimination ability in musicians of
      different specialties].
AB  - The frequency discrimination capacity of 63 musicians of different specialties
      (singers, string players, wood and brass players, pianists and rhythm teachers)
      was investigated using a binaural frequency discrimination test. Statistically
      significant differences between the groups of musicians were found. The string
      players revealed the highest tuning reproducibility. The results show that
      frequency discrimination capacity is influenced by specific phenomena of the
      instrumental education.

PMID- 9172847
TI  - Preoperative ICU tours: are they helpful?
AB  - BACKGROUND: Although preoperative education decreases the anxiety of patients and
      family members, the usefulness of a preoperative tour of the ICU has not been
      studied. In this study, the effect of an ICU tour on the anxiety levels of
      patients (n = 92) and family members (n = 91) before and after cardiac surgery
      was examined. METHODS: Using a pretest-posttest quasi-experimental design,
      patients and family members were assigned to a control group, which received
      preoperative teaching only (patients, n = 48; family members, n = 48), or to an
      experimental group, which received preoperative teaching with an ICU tour
      (patients, n = 44; family members, n = 43). Patients and family members completed
      two measures of anxiety, the State Trait Anxiety Inventory and a visual analog
      scale, before and after the intervention. After their first postoperative visit,
      family members completed the measures again. Repeated measures analysis of
      variance was used to compare anxiety levels after the intervention. In addition,
      patients completed the Patient Perception of the ICU Tour Questionnaire after
      transfer from the ICU. RESULTS: Although patients and family members had a
      decrease in anxiety after cardia surgery teaching, the decrease was not due to an
      ICU tour. However, the majority of patients who toured the ICU perceived the tour
      as beneficial and recommended a tour for future patients. CONCLUSIONS: ICU tours
      are included in many cardiac surgery educational programs. The majority of
      patients in this study perceived a benefit or a future benefit from an ICU tour,
      even though the tour did not significantly reduce the anxiety of the patients or
      family members.

PMID- 9172848
TI  - Psychological factors and survival in the cardiac arrhythmia suppression trial
      (CAST): a reexamination.
AB  - BACKGROUND: Evaluating the independent effects of psychosocial and physiological
      factors on survival of cardiac patients is difficult because it requires
      obtaining extensive physiological and psychosocial data and long-term follow-up
      of high-risk patients. OBJECTIVES: To examine the independent contributions of
      psychosocial and physiological status to survival of patients who had had
      myocardial infarction. METHODS: The sample consisted of 348 patients in the
      Cardiac Arrhythmia Suppression Trial who had asymptomatic ventricular arrhythmias
      after myocardial infarction. Psychosocial status was assessed with the Social
      Support Questionnaire-6, Social Readjustment Rating Scale, State-Trait Anxiety
      Inventory, Self-Rating Depression Scale, Jenkins Activity Survey, and Expression
      of Anger Scale. Physiological data included measurement of left ventricular
      ejection fraction; history of previous myocardial infarction, congestive heart
      failure, and diabetes; and results of Holter monitoring. RESULTS: At the first
      follow-up, after the effect of the physiological predictors was controlled for,
      psychosocial factors were significant independent predictors of survival. Among
      men in the nonactive medication group (n = 263), higher state anxiety, lower
      anger outward, more past life events, and lower expectations of future life
      events were predictors of mortality. Data suggested that the relationship of
      anger to mortality might differ for men and women. Increases in past life events
      and depression from baseline to first follow-up were greater among those who died
      than among those who lived. CONCLUSION: Among patients who had asymptomatic
      ventricular arrhythmias after myocardial infarction, psychological status during
      the period after infarction contributed to mortality beyond the effect of
      physiological status. The results reaffirm the critical interrelationship between
      mind and body for cardiovascular health.

PMID- 9172850
TI  - The effect of turning and backrub on mixed venous oxygen saturation in critically
      ill patients.
AB  - OBJECTIVE: To examine the effect of a change in body position (right or left
      lateral) and timing of backrub (immediate or delayed) on mixed venous oxygen
      saturation in surgical ICU patients. METHODS: A repeated-measures design was used
      to study 57 critically ill men. Mixed venous oxygen saturation was recorded at 1
      minute intervals for 5 minutes in each of three periods: baseline, after turning,
      and after backrub. Subjects were randomly assigned to body position and timing of
      backrub. Subjects in the immediate-backrub group were turned and given a 1-minute
      backrub. Mixed venous oxygen saturation was measured at 1-minute intervals for 5
      minutes at two points: after the backrub and then with the patient lying on his
      side. For subjects in the delayed-backrub group, saturation was measured at 1
      minute intervals for 5 minutes at two different points: after the subject was
      turned to his side and after the backrub. RESULTS: Both position and timing of
      backrub had significant effects on mixed venous oxygen saturation across
      conditions over time. Subjects positioned on their left side had a significantly
      greater decrease in saturation when the backrub was started. At the end of the
      backrub, saturation was significantly lower in subjects lying on their left side
      than in subjects lying on their right side. The pattern of change differed
      according to the timing of the backrub, and return to baseline levels of
      saturation after intervention differed according to body position. CONCLUSIONS:
      Two consecutive interventions (change in body position and backrub) cause a
      greater decrease in mixed venous oxygen saturation than the two interventions
      separated by a 5-minute equilibration period. Turning to the left side decreases
      oxygen saturation more than turning to the ride side does. Oxygen saturation
      returns to clinically acceptable ranges within 5 minutes of an intervention. In
      patients with stable hemodynamic conditions, the standard practice of turning the
      patient and immediately giving a backrub is recommended. However, it is prudent
      to closely monitor individual patterns of mixed venous oxygen saturation,
      particularly in patients with unstable hemodynamic conditions.

PMID- 9172849
TI  - Effects of inhaled nitric oxide in patients with hypoxemia and pulmonary
      hypertension after cardiac surgery.
AB  - BACKGROUND: Cardiopulmonary bypass can increase pulmonary vascular tone and
      decrease ventilation-perfusion matching by impairing the pulmonary endothelial
      production of nitric oxide. OBJECTIVES: We tested the hypothesis that inhalation
      of exogenous nitric oxide decreases the ratio of mean pulmonary arterial pressure
      to mean system arterial pressure and the intrapulmonary shunt fraction and
      increases the ratio of arterial blood oxygen tension to fraction of inspired
      oxygen in patients in whom the ratio of mean pulmonary arterial pressure to mean
      systemic arterial pressure is more than 0.50, and the ratio of arterial blood
      oxygen tension to fraction of inspired oxygen is less than 300 mm Hg in the first
      24 hours after cardiopulmonary bypass surgery. METHODS: Only those patients who
      had estimates of the ratio of mean pulmonary arterial pressure to mean systemic
      arterial pressure and the ratio of arterial blood oxygen tension to fraction of
      inspired oxygen determined preoperatively were enrolled. Hemodynamic variables
      were recorded, and blood samples were obtained for oximetric analysis 5 minutes
      before and 30 minutes after inhalation of nitric oxide began. The concentration
      of nitric oxide inhaled was maintained at 20 parts per million. The data were
      analyzed by using Friedman's repeated measures analysis of variance. RESULTS:
      Thirteen patients were enrolled in the study. The mean preoperative ratio of mean
      pulmonary arterial pressure to mean systemic arterial pressure was 0.63 +/- 0.08
      (standard error of the mean), and the mean preoperative ratio of arterial blood
      oxygen tension to fraction of inspired oxygen was 131 +/- 15 mm Hg. No
      differences between preoperative and postoperative values were detected.
      Inhalation of nitric oxide decreased the ratio of mean pulmonary arterial
      pressure to mean systemic arterial from 0.53 +/- 0.07 to 0.39 +/- 0.5 and
      increased the ratio of arterial blood oxygen tension to fraction of inspired
      oxygen from 167 +/- 35 mm Hg to 235 +/- 45 mm Hg. Inhalation of nitric oxide also
      decreased the intrapulmonary shunt fraction from 0.29 +/- 0.05 to 0.19 +/- 0.04.
      CONCLUSIONS: Inhalation of nitric oxide selectively decreases pulmonary vascular
      tone and increases ventilation-perfusion matching in patients with persistent
      pulmonary hypertension and hypoxemia after surgery requiring cardiopulmonary
      bypass. Inhalation of nitric oxide may be a valuable adjunctive therapy for these
      patients.

PMID- 9172851
TI  - Control of infections caused by drug-resistant organisms in critical care.
AB  - The emergence of antibiotic-resistant pathogens has been an ongoing concern of
      infection-control and infectious disease practitioners. Infections caused by
      these organisms increase costs and may result in poorer outcomes for patients.
      Efforts to contain the problem of infections caused by drug-resistant organisms
      have two objectives: to optimize antibiotic use and to prevent transmission
      through effective infection-control practices.

PMID- 9172852
TI  - Treatment of malignant bronchial or mediastinal obstruction in comatose patients
      on life support.

PMID- 9172853
TI  - Baccalaureate nurse educators' and critical care nurse managers' perceptions of
      clinical competencies necessary for new graduate baccalaureate critical care
      nurses.
AB  - BACKGROUND: Although nurse educators and nurse managers have disagreed about
      which clinical competencies are necessary for new graduates to begin working in
      critical care, the competencies are in need of revision and reassessment.
      OBJECTIVES: To validate a list of beginning-level competencies and to compare
      baccalaureate nurse educators' and critical care nurse manager's current
      perceptions of beginning clinical competencies for new baccalaureate graduates in
      critical care settings. METHODS: An expert panel of nurses from across the United
      States critiqued a questionnaire about which clinical competencies were
      considered relevant to critical care nursing practice. The revised questionnaire,
      containing 105 clinical competencies, was mailed to a randomly selected sample
      across the United States. Forty-one baccalaureate nurse educators and 41 critical
      care nurse managers completed the mail survey questionnaire (94% response rate)
      by rating the necessity ("essential," "desired," or "not required") of the
      clinical competencies for new baccalaureate nurses. RESULTS: A high degree of
      agreement was generally seen between nurse educators and nurse managers on the
      necessity ratings of the 105 competencies. The majority of nurse educators and
      nurse managers rated 81 of the 105 competencies as either "essential" or
      "desirable." Only five competencies showed considerable disagreement between
      nurse educators and nurse managers, and none of these competencies were rated
      "essential" by more than a few raters in either group. CONCLUSIONS: The agreement
      between nurse educators and nurse managers supports a competency list for
      baccalaureate nursing curricula and hospital inservice programs to integrate new
      graduates into critical care.

PMID- 9172854
TI  - Endothelium: the key to medical management of coronary artery disease.

PMID- 9172855
TI  - Sailing close to the wind.

PMID- 9172856
TI  - International normalized ratio in anticoagulant therapy: understanding the
      issues.
AB  - Recently, a change in anticoagulation therapy occurred that is still partially
      ignored by the healthcare community. Understanding the controversy over the use
      of the internal normalized ratio in monitoring patients receiving warfarin
      therapy is important for nurses who provide care to these patients. Five
      questions related to current monitoring of patients treated with anticoagulants
      are addressed. Nurses must recognize the importance to their practice of changes
      in laboratory methods and move toward using the most useful measures available to
      influence patients' outcomes. The international normalized ratio is the most
      appropriate way to evaluate the effects of warfarin therapy. All healthcare
      providers should use this ratio as the standard in evaluating the effects of
      anticoagulation therapy.

PMID- 9172857
TI  - The impact of routine chest radiography on ICU management decisions: an
      observational study.
AB  - OBJECTIVE: To document the impact of routine daily chest radiographs on treatment
      decisions in a medical ICU. METHODS: The study sample consisted of 200
      consecutive patients in an 11-bed medical ICU of a university-affiliated teaching
      hospital. During the study period, each patient's current and previous chest
      radiographs were reviewed in the ICU during morning rounds. A computerized
      digital video display system was used. Changes in therapy made as a consequence
      of this review were recorded. RESULTS: A total of 471 chest radiographs were
      reviewed. The patients' mean score on the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) was 14.6 +/- 2.5, and the mean length of stay in the
      ICU was 3.6 days +/- 2.1 days (range, 11-24 days). A change in therapy was made
      on the basis of information obtained from review of the chest radiograph in 174
      instances (37% of radiographs). The most frequent therapeutic interventions were
      use of a loop diuretic to treat pulmonary edema (26%), repositioning of an
      endotracheal tube (24%), and diagnostic studies to determine the cause of a new
      pulmonary infiltrate (16%). At least one change in therapy was made for 91 (66%)
      of the 138 intubated patients but for only 14 (23%) of the 62 nonintubated
      patients; this difference was significant. Differences among diagnostic groups
      were largely a reflection of the number of patients who were intubated.
      CONCLUSION: Routine daily chest radiographs may be justified in critically ill
      patients in a medical ICU because for a large proportion of these patients
      management decisions are made on the basis of information obtained from the chest
      radiograph. This observation may be applicable only to ICUs that have a high
      turnover of patients who are in the unit for a short time.

PMID- 9172859
TI  - Proceedings of the 20th International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. San Francisco, California, 16-21 June 1996.
      Part II.

PMID- 9172858
TI  - Outcomes of long-term ventilator patients: a descriptive study.
AB  - BACKGROUND: Long-term ICU patients who require prolonged mechanical ventilation
      are a growing segment of the in-hospital population. Despite recognition that
      this population is costly to care for no systematic research has been done on the
      characteristics, outcomes, and disposition of these patients after they leave the
      hospital. OBJECTIVE: To describe clinical and sociodemographic characteristics
      and outcomes of ICU patients who require long-term (5 days or more) mechanical
      ventilation while in the hospital. METHODS: A prospective, longitudinal
      descriptive design was used to study 57 ICU patients who required 5 days or more
      of continuous mechanical ventilation while in the hospital. Clinical and
      sociodemographic data were collected at the time of enrollment. Patients were
      followed up for up to 6 months after discharge from the hospital to ascertain
      disposition and morality. RESULTS: On average, patients had a hospital stay of
      almost 6 weeks and required mechanical ventilation for approximately 4 weeks;
      43.9% of the patients died in the hospital. None of the patients discharged from
      the hospital were able to return home initially without assistance. By 6 months
      after discharge, more than 50% of the original sample and died, 9% resided in an
      institution, and 33% were living at home. CONCLUSIONS: A large percentage of ICU
      patients who require 5 days or more of mechanical ventilation die in the
      hospital, and many of those who live spend considerable time in an extended-care
      facility before they are discharged to their homes. These likely outcomes of
      patients who require long-term ventilation should be discussed with patients and
      their families to assist them in making informed decisions.

PMID- 9172860
TI  - [The cloning and expression of the beta-galactosidase gene of Candida
      pseudotropicalis yeasts in Escherichia coli cells].
AB  - The gene encoding the beta-galactosidase of the yeast Candida pseudotropicalis
      was cloned on YEp13 shuttle vector as the XhoI-fragment of chromosomal DNA of
      about 9.5 kb. SalGI-fragment of 7.5 kb with the beta-galactosidase gene was
      subcloned from the pG2 hybrid plasmid obtained into the pBR322 plasmid and then
      shortened to give 5.2 kb via deletion on XhoI site. This plasmid constructed was
      designated pBG2-1. In DNA/DNA hybridization studies the appearance of one XhoI
      fragment and seven EcoRI-fragments in DNA C. pseudotropicalis hybridized to the
      DNA cloned fragment and the absence of hybridization to DNA Escherichia coli were
      shown. The beta-galactosidase activity of cells of transformants of E. coli was
      lower than the activity of prototrophic strain. The beta-galactosidase
      biosynthesis in transformants was insignificantly induced by lactose and IPTG and
      was not repressed by glucose.

PMID- 9172861
TI  - [The composition of the cellular fatty acids in bacteria of the genera Yersinia
      and Francisella].
AB  - The studied strains of Yersinia pseudotuberculosis (5 st.), Y. enterocolitica (2
      st.), Y. intermedia (1 st.), Y. frederiksenii (1 st.), Y. kristensenii (1 st.)
      and Y. ruckeri (1 st.) have similar fatty acid profiles of cells mainly
      represented by straight chain and cyclopropanic fatty acids with chain of 12 to
      19 carbon atoms. Prevalence of C16:1, C16:0, C17v, in the spectrum and C18:1
      under growth in meat-peptone broth are observed. Strains of Y. pseudotuberculosis
      as well as the already studied vaccine strain Y. pestis differ from yersiniae of
      other species by the lower level of dodecanoic acid. Bacteria of species
      Francisella tularensis (6 st.) are characterized by a wide range of straight
      chain saturated and monounsaturated fatty acids with 10-26 carbon atoms.
      Yersiniae and francisellae preserve the proper fatty acid profiles under
      cultivation on various nutrient media and on the same medium (agarized medium
      with aminopeptide). Results obtained confirm close relationship of yersiniae of
      the studied species as well as phylogenetic remoteness and taxonomic isolation of
      yersiniae and francisellae.

PMID- 9172862
TI  - [The modification of the internucleotide relations of antisignature
      oligodeoxyribonucleotides as a means of increasing their resistance to nuclease
      cleavage in mollicute cells].
AB  - Modifications in 5'- and 3'-ends and internucleotide bondings of antisignature
      oligodesoxyribonucleotides have been studied for their resistance to nuclease
      cleavage in cells of Acholeplasma laidlawii PG-8 and Mycoplasma fermentans PG-18.
      It is shown that adding of benzylamide grouping to the 5'-end of oligonucleotides
      increases their half-life period in the studied mollicute cells to 15 h. S-methyl
      modification of 3'-end of antisignature oligonucleotides did not take essential
      effect on the process of degradation of the given compounds in the mollicute
      cells. Considerable increase of stability in the studied cels of thio- and
      dithiophosphate analogues of oligodesoxyribonucleotides has been detected.

PMID- 9172864
TI  - [The action of bacterial antagonists on the aerobic microflora of human skin].
AB  - The authors have investigated antagonistic action of museum strains-antagonists
      Bacillus subtilis 2896, B. licheniformis 254 and Escherichia coli M-17 against
      698 strains of staphylococci, 518 micrococci, 315 corynebacteria, 74 aerobic
      bacilli and 26 enterobacteria isolated from the surface of stomach and skin of
      102 healthy people of different sex. The investigations have shown that B.
      subtilis 2896 and E. coli M-17 were most active: they inhibited the growth of
      micrococci, corynebacteria, bacilli, enterobacteria and pseudomonads. Bacteria B.
      licheniformis have manifested the less antagonistic effect of representatives of
      skin microbiocenoses. These are B. subtilis and E. coli M-17 that are recommended
      for clinical testing with the purpose of correction of skin microbiocenoses and
      for preventing from the development of pyo-septic complications of skin.

PMID- 9172863
TI  - [The activity of a number of anabolic metabolism enzymes in Staphylococcus aureus
      strains containing plasmids of antibiotic resistance].
AB  - Activity of a number of enzymes participating in the processes of structure
      metabolism and dynamics of inclusion of 14C-aspartate in initial strain of
      Staphylococcus aureus sensitive to antibiotics and strains containing plasmids of
      resistance to various antibiotics have been comparatively studied. An increase in
      activity of fumarate-hydratase, acetyl-KoA-carboxylase, aspartate
      aminotransferase and well as true increases (by the rate of inclusion of 14C
      aspartate in a number of strains containing plasmids) of resistance to
      antibiotics as compared to plasmid-less variant are shown. This evidence for
      strengthening of biosynthetic function of a cycle of tricarbonic acids and,
      allowing for extremely low activity of alpha-ketoglutarate dehydrogenase, one can
      suppose that an open cycle of tricarbonic acids functions in the given strain of
      staphylococcus. The increase of the level of acetyl-KoA-carboxylase activity
      evidences for the intensification of lipid synthesis in antibiotic-resistant
      staphylococci as compared to the sensitive variants.

PMID- 9172865
TI  - [The development of a latex antigenic diagnostic agent for the serological
      determination of tuberculous infection].
AB  - Using two tuberculoproteins, phosphatide and polysaccharide antigens obtained
      from culture filtrate of pathogenic and vaccinal strains of Mycobacterium of
      human and bull types and standard monodispersed particles of latex modified by
      different chemical groups, the technology of creation of latex antigenic
      preparations for serologic express diagnosis of tuberculosis was elaborated. This
      method is based on the reaction of latex agglutination. Latex diagnostic
      preparation possesses sufficiently high serologic activity and specificity. The
      spectrum of microbacterial antigens allows one to characterize the status of
      immunity of patients with different forms of tuberculosis and to determine the
      degree of the process activity.

PMID- 9172866
TI  - [The toxin-containing filtrates from the culture broths of clinical strains of
      Corynebacterium diphtheriae].
AB  - Composition as well as toxicity and antigenicity of toxin-including filtrates of
      6 circulating strains of Corynebacterium diphtheriae, isolated in 1992-1994 in
      the city of Kharkiv have been studied as compared with production strain PW-8. It
      is shown that toxicity of filtrates of circulating strains was analogous of
      toxicity of the strain PW-8 (100 dlm) or lower (45 dlm). Antigenicity of four
      strains which was expressed in if units proved to be higher than that of the
      production strains and it was considerably higher in two strains isolated from
      adults who died from diphtheria. The methods of gel-filtration and
      immunoprecipitation were used to establish differences between strains in their
      capacity to preferential accumulation of different molecular forms of toxin under
      stationary cultivation.

PMID- 9172867
TI  - [The biological properties of adsorbed and nonadsorbed OH-agglutinating sera for
      the identification of Rahnella aquatilis bacteria].
AB  - The paper presents the production technology of rabbit hyperimmune adsorbed and
      unadsorbed OH-agglutinating sera for Rahnella aquatilis bacteria identification.
      Results are reported for such biological characteristics of the new preparations
      as their specificity and agglutination activity (titer). It is shown that
      cultures R. aquatilis ATCC 33989 and ATCC 33071 possess marked immunogenic
      properties and E.cloaceae 1903 strain has good absorptional ones, that enables
      one to employ them for production of agglutinating sera. It is concluded that new
      adsorbed and unadsorbed OH-agglutinating sera may be used for microbiological
      diagnosis of diseases caused by R. aquatilis.

PMID- 9172868
TI  - [The inductive immunosuppressive activity of the nonspecific lipopolysaccharide
      fraction of virulent Shigella sonnei].
AB  - The influence of lipopolysaccharide (LPS) fraction (molecular weight 50-70 kD) of
      virulent Shigella sonnei on bacterium ability to suppress delayed-type
      hypersensitivity (DTH) to xenogenic test-antigen in mice has been studied. It is
      found that single injection of LPS-fraction or bacteria does not inhibit DTH.
      Intraperitoneal injection of LPS-fraction together with avirulent S. sonnei
      causes DTH inhibition in mice and at the same time the injection of LPS-fraction
      together with Staphylococcus or Pseudomonas (extracellular parasites) does not
      render influence on DTH levels. There is a possibility of LPS-fraction conversion
      from active to non-active state and back after treatment by trichloracetic acid,
      phenol or redox system. It is assumed that in Shigella sonnei infection avirulent
      enteroinvasive bacteria can be involved in immunopathological process due to
      activity of non-specific fraction of S. sonnei LPS.

PMID- 9172869
TI  - [A comparison of nutrient media for the cultivation of Neisseria gonorrhoeae].
AB  - It is established that the highest growth peculiarities are characteristic of the
      nutrient medium for gonococcus isolation of the following composition: MPA of
      fresh bovine hearts enriched with casein hydrolysate, yeast autolysate, cattle
      serum (CS) and 0.01% addition of sodium humate. The given nutrient medium has the
      highest diagnostic potentialities. A possibility to change bovine hearts MPA for
      swine heart MPA, CS serum and plasmol. The nutrient medium on the basis of fresh
      swine heart, enriched with plasmol, casein hydrolysate and yeast autolysate may
      be used to isolate and cultivate gonococci under the laboratory conditions.

PMID- 9172870
TI  - [Surface-active substances in the arsenal of agents against AIDS].
AB  - Only nucleoside analogues such as zidovudine have been widely used to improve the
      clinical state of patients with AIDS till now. Their use has a number of
      eliminations. Nevertheless, the anti-HIV properties of many different substances
      have been shown. Some of them contain hydrophobic and polar parts of molecules
      and can be considered as surfactants. Detergents (DT) (among them Ukrainian
      preparation Myramistin), modified phospholipids, polyene antibiotics (such as
      Nystatin A), lipophilic muramyl peptides (LMP), saponins (S) and some other
      surfactants have been described as inhibitors of HIV replication. Moreover, LMP
      and S are the potent adjuvants and are probable candidates for vaccines against
      HIV. Adjuvant activities of some DT have been shown recently as well. We hope
      that elaboration of new adjuvants with strong anti-HIV properties is an
      attractive and manageable aim.

PMID- 9172871
TI  - [Clinical signs of severe malaria in a pediatric hospital in Ouagadougou].
AB  - During the period of transmission of malaria, from August to November of 1993 and
      1994, we conducted a study to determine the frequency of the clinical forms of
      severe and complicated malaria. The study involved children, from 6 months
      through 15 years old, admitted to the pediatric ward of the hospital in
      Ouagadougou, Burkina Faso. The criteria for inclusion followed the definition of
      severe malaria stated by the World Health Organization. We carefully noted the
      symptoms and signs on admission. Of the total of 719 children enrolled in the
      study, there was a prevalence of children under 5 years old. The most frequent
      clinical forms were those of coma (377 cases, 52.4%), prostration (268 cases,
      37.3%), convulsion (152 cases, 21.4%), anemia (115 cases, 15.9%), and
      hypoglycemia (55 cases, 10.3%). No renal failure form was observed. We also
      observed the respiratory distress form (35 cases, 4.9%) and the hemorrhagic form
      (11 cases, 1.5%). Malaria remains a major cause of childhood morbidity and
      mortality in the developing world. Early therapeutic management of febrile
      attacks with chloroquine would reduce the incidence of severe and complicated
      malaria.

PMID- 9172872
TI  - [Current aspects of extrauterine pregnancy in Nosy Be (Madagascar), from November
      1993 to February 1995].
AB  - We present the current aspects of ectopic pregnancies in Nosy Be, Madagascar, and
      possible solutions. Ectopic pregnancies are problems of public health here as in
      many developing countries. Nosy Be is a small island northwest of Madagascar and
      is part of Madagascar's territory. This was a prospective, continuous, nonrandom,
      open study of 27 ectopic pregnancies observed on this island; all were confirmed
      by laparotomy during 16 months from November 1993 to February 1995 in the
      department of general surgery in the hospital. The selected criteria of diagnosis
      were epidemiological, clinical and histological. Aside from the antecedent of
      genital infections, apparently the clinical lists of illnesses on the island are
      distinct from those in industrialized countries. In Nosy Be, the majority of
      these patients were young women having a history of genital infections. The
      diseases were later diagnosed at the stage of an intraperitoneal hemorrhage with
      shock. The diagnoses were exclusively clinical, because the hospital of Nosy Be
      is lacking materials and does not have equipment for measuring human chorionic
      gonadotrophin, or performing ultrasonography and celioscopy. Also, there is no
      blood bank. Thus we suggest the following. First, a blood bank should be
      established. Secondly the conditions of early diagnosis of the disease should be
      improved by providing information and education and an early examination of
      pregnant women. Yet these measures will be adequate only with the acquisition of
      complementary equipment for measuring human chorionic gonadotrophin, and
      performing ultrasonography and celioscopy. Thirdly, to decrease the frequency of
      the disease, the public needs to be informed and educated about the dangers of
      genital infections, their primary and secondary prevention and the necessity of
      their appropriate treatment.

PMID- 9172873
TI  - [Ultrasonography of changes in the retroperitoneal vessels and perivascular
      spaces during retroviral infection: preliminary results].
AB  - The abdomen in patients with acquired immunodeficiency syndrome (AIDS) is subject
      to various damage. In AIDS patients, manifestations in the retroperitoneal
      region, including apparent changes in the pancreas, kidney and lymph nodes, have
      been well described in the radiological literature. However, abnormalities of the
      vessels and perivascular spaces have not been well investigated in this syndrome.
      We performed abdominal sonography in 10 patients who were seropositive for HIV.
      They had no history of known risk factors such as drug abuse or homosexuality.
      Also, 4 healthy male controls were examined for comparison. Our aim was to
      demonstrate and to characterize the pathological changes of the retroperitoneal
      vessels and perivascular spaces from sonographic observations. The sonographic
      evaluation included determination of the morphologic and dynamic aspects of the
      aorta, vena cava and superior mesenteric vessels. The echostructure of the
      perivascular spaces was analyzed. In this prospective and preliminary study, we
      have not considered the presence of an AIDS condition. We have precisely analyzed
      the upper umbilical areas. In all cases, there were supposed to be the same
      landmarks. The sonographic scans were obtained through the left renal and
      mesenteric vessel areas, essentially through axial scans. In all 10 patients,
      sonography showed at least two abnormalities. Three patients had abnormal
      echostructural changes in all the sites. The images showed echostructural
      disorganization with poor definition and "fuzzy" and "dirty" aspects of the
      retroperitoneal vessels and perivascular spaces. The aorta was normal in 2
      patients and abnormal in 8 patients with diminished hyperechography and
      regularity of the aortal wall. The aortic diameter was smaller than 1.5 cm in 7
      cases, with a significant attenuation of the beating of the aorta. Despite these
      abnormalities, the aorta had a normal left paramedian position ahead of the
      rachis. The inferior vena cava was normal in 1 case and abnormal in 9 cases with
      diminished hyperechography and regularity of the wall. The vena cava position was
      normal in 4 cases, displaced in 6, and laminated in 3. The superior mesenteric
      vessels were abnormal in 8 cases, with poorly defined aims in 6, an indefinite
      position in 2, and spreading in 2. Adenopathy was present in 6 patients, multiple
      in 5 and singular in 1 case. A retrocaval location was always observed. A
      perivascular infiltration and thickening was noted which was diffuse in 6 cases
      and micronodular in 1 case. From our observations, we conclude that these
      echostructural changes could be related to AIDS. However, further studies are
      necessary to confirm these observations and to determine if this sonographic
      pattern may be seen during the course of the disease. This is the first study to
      our knowledge which stressed the echostructural changes of the retroperitoneal
      vessels and perivascular spaces in patients with AIDS.

PMID- 9172874
TI  - [The financial costs of health care: a follow-up survey of women having a high
      risk delivery].
AB  - Our aim was to analyze the financial costs of health care for women in labor
      transferred to primary referral maternity units in childbirth at risk. Another
      aim was to consider the willingness of women and their husbands to financially
      save and support the increasing costs of health care. For 15 consecutive days,
      medical students interviewed all women transferred for a risky delivery in 12 of
      the 17 primary referral maternity units in Burkina Faso. The median cost for
      transferring the women and their necessary health care was approximately 30,500
      CFA. The median cost for the kit of surgical supplies was 15,000 CFA; the costs
      of medicine and transportation fare for the woman and her husband were 14,000 CFA
      and 9,800 CFA, respectively. The median cost for the health care of the newborn
      was 2,400 CFA. When the decision for the transfer was made, the necessary money
      to pay for the expenses was available for only 40 out of 79 women. Women and
      their husbands were willing to save for health care either through existing
      community institutions such as groups of villagers and popular savings
      developments (69 women and men); or through annuity schemes to be created (33
      women and men); or through banks (4 women and men). Four women and 6 men refused
      to contribute because of previous experiences of poor management of collective
      funds. The average savings were low and insufficient to cover the expected
      expenses for the transfer and care of the women. The savings were reserved for
      payment of the transportation fare for the women and their husbands to the
      referral units (21 women and 20 men), prescriptions (9 women and 5 men), the
      medical consultation (1 woman), and to provide for both (37 women and 39 men).
      The costs of health care are expensive. The poverty of the couple facing an
      urgent problem of life or death made them discover new options for investing in
      their available community associations such as groups of villagers and popular
      savings developments and other options such as annuity schemes. A policy directed
      towards the involvement of these populations could facilitate the transfer and
      treatment of women during their pregnancy.

PMID- 9172875
TI  - [The impact of curtains impregnated with deltamethrin on the vectors and
      morbidity of malaria: results in Ankazobe, on the plateaus of Madagascar].
AB  - To evaluate the efficacy of deltamethrin impregnated curtains on malaria
      morbidity in a low transmission area, we studied volunteer families in the
      village of Ankazobe in the Madagascar Highlands from February 1993 to June 1994.
      After randomization, we provided 46 houses having 244 inhabitants with
      impregnated curtains (I) and 45 others having 257 inhabitants with nonimpregnated
      curtains (NI) as controls. We first estimated the number of mosquito bites in the
      protected versus nonprotected households. Every month, we captured mosquitos on
      humans in 6 houses per night for 4 nights. For the I group compared to the NI
      group, the number of bites by the Anopheles funestus vector per human per night
      was reduced by 64% in 1993 and 39% in 1994. We also analyzed the malaria
      morbidity. Malaria morbidity was defined as patients having both temperatures
      greater than 37.5 degrees C and Plasmodium falciparum parasitemia greater than
      1500/microliter with clinical symptoms. From February to July 1993, we observed
      no significant difference in morbidity: there were 103 cases of malaria among 244
      inhabitants of the I group and 117 cases among 257 inhabitants of the NI group.
      However, during the period of highest transmission from March to May in 1993,
      there were significantly fewer cases in the I group (68) than in the NI group
      (94). From January to June 1994, the difference was clear: only 35 malaria cases
      were observed among the 208 inhabitants of the I group as compared to 65 cases
      among the 223 inhabitants of the NI group (Chi square = 9.17, p = 0.0024).
      Inhabitants of the I group could have been contaminated before the curtains were
      set up. After treatment of the cases and use of curtains during the second year,
      we observed a reduction in the number of mosquito bites and malaria cases. The
      small size of the trial made the interpretation of the data difficult.
      Nonetheless, the results tentatively support the use of impregnated curtains as
      an antimalaria tool in an integrated control program.

PMID- 9172876
TI  - [The development of public health education: the Mauritius experience].
AB  - A public course has been initiated in 1990 in Mauritius for covering the national
      growing needs of public health specialists. This training course was organized
      jointly by the Ministry of Health, the University of Bordeaux II and the French
      Cooperation. After 3 sessions dedicated specifically to the Mauritian physicians,
      the course has been re-designed for the needs of the other countries of the
      region. A feasibility study performed in 1994 in the countries of the Indian
      ocean region showed that during the past decade, the district level had become
      the focus point to integrate the health programs. This process has progressively
      transferred a wider and stronger part of the responsibilities from the central
      level to the district level and the survey showed that most of the health
      district managers were physicians that did not have the proper background for
      carrying such responsibilities. According to these results, a course curriculum
      was created by the Mauritian Ministry of Health and the University of Bordeaux II
      and submitted to various organisms supporting health program development in the
      region. This proposal was strongly supported by several agencies (the french
      Cooperation, Unicef, WHO, World Bank...) who agreed to sponsor candidates for
      that training course. The first session was organized in 1995, a second one in
      1996. This training course is targeted to the medical doctors who are in charge
      of the management of health services at the district level. It is divided in two
      parts: A six-weeks intensive training course performed in Mauritius that include
      formal teaching and practical exercises in small groups for a total of 210 hours.
      The curriculum is mainly targeted on the various aspects of management as the
      management of health information (biostatistics epidemiology and computing), the
      management of human resources, financial resources and material resources. In
      addition to these main topics, there is an introduction to pedagogy,
      communication skills and applied research methodology. Following this six-weeks,
      training the students come back to work in their country and have 8 months to
      perform a thesis supervised by a local public health specialist. The subject of
      the thesis has to be closely related with one of the topic taught and should
      provide an obvious improvement for the public health situation in the district
      where this physician is acting. In 1995, 22 candidates attend to the course (13
      from Madagascar, 4 from Mauritius, 3 from Comoros, 1 from Angola, 1 from
      Equatorial Guinea and 1 from Tchad), 19 had successively completed all the
      modules and got the diploma of public health delivered by the University of
      Bordeaux II. This diploma has been recognized as an equivalent to a master in
      public health in Mauritius. The evaluation of the courses-performed by the
      students, the teachers and the financial agencies gave a very positive results
      although the workload was considered as too important for a six-weeks training
      course. The recommendations of the 1995 session were included in the 1996
      programs which is still on going for 23 candidates. The 97 session will probably
      extend the number of students up to 40, divided in 4 subgroups for practical
      exercises. In parallel to the course, a quarterly bulletin will be created and
      sent to the present and past candidates of this course in order to support a
      continuous medical education training program targeted to the district
      physicians.

PMID- 9172877
TI  - [Attendance at a health center by clandestine prostitutes in Djibouti].
AB  - The extent of clandestine prostitution in Djibouti is difficult to evaluate. Due
      to the secrecy of the prostitutes and often their low level of education, the
      follow-up of these patients is also difficult. A sexually transmitted disease
      clinic specialized in the treatment of prostitutes and their customers has been
      established in Djibouti since 1963. We tried to evaluate the available data on
      the clandestine prostitutes attendance at the center. The population was young
      with a mean age of 23 years. Fifty percent had children and 60% were divorced or
      separated. Ninety-one percent were Ethiopian and 73% lived in the same district
      of the city of Djibouti. Almost half of them were HIV positive. The duration of
      residence in Djibouti before the first visit to the clinic varied widely with a
      median of 12 months. However, the total duration of prostitution before the first
      visit was shorter with a median of 3 months. The complaint at the first visit was
      most often minor. Among the prostitutes who first came to the center in 1993,
      half of them came only once. The overall duration of follow-up was 8 months, for
      an average of 3.7 visits per patient. Alternatively, 20 patients had more than 10
      consultations and this represented one third of the consultations given to
      previous patients. This last group is the only one which tended to respect the
      monthly visits proposed to each patient at the first consultation. The other
      patients seemed to come only when they felt ill. The routine statistical
      activities which separately counted the new and previous patients gave an
      optimistic but faulty impression: these showed an increase in the total number of
      patients and also an increase in the percentage of previous patients visiting
      (from 42 to 69% between 1988 and 1994). It is difficult to evaluate the follow-up
      of such a mobile population. The few patients known for their fidelity contrasted
      with the fact that half of the patients had visited the center only once. This
      low frequency of visitation could be due to either the management of the center
      or to the lack of proximity of the contacts within the districts.

PMID- 9172878
TI  - [The plague in Madagascar: epidemiologic data from 1989 to 1995 and the national
      control program].
AB  - After briefly reviewing the history and epidemiological cycle of the plague in
      Madagascar, we report a detailed analysis of 5,927 suspected cases of plague
      observed from 1989 to 1995 (average of 846 cases per year). Of those, 1,337
      individuals (average of 191 cases per year) were confirmed (by isolation of
      Yersinia pestis) or indicated to be probable for plague (by positive smears).
      Since 1994, we observed an increasing number of confirmed and probable cases (252
      cases in 1995). Most of the cases occurred between October and April in the
      central highlands, inside a geographical triangle limited by Alaotra lake, Itasy
      lake and the city of Fianarantsoa. Two exceptional epidemics occurred in the
      harbor of Majunga in 1991 and 1995. The bubonic plague was the most frequent
      clinical from (91.3%), with primarily an inguinal localization (67.8%). The mean
      case fatality rate was 19% of the confirmed or probable cases (14.8% for the
      bubonic form and 57.1% for the pneumonic form). The bubonic plague was
      significantly more frequent between the ages of 5 and 14 years, as compared to
      the general population, while the pneumonic plague was more frequent over 15
      years of age. Males were more effected by the bubonic form, as the sex ratio
      (m:f) was 1.3. The national control program for plague is being strengthened to
      improve 1) the patient's early diagnosis and care system; 2) the measures for the
      prevention of epidemics; 3) the epidemiological surveillance; and 4) the studies
      on the biology of the plague vectors, rodents and fleas, and the agent, bacilli,
      in Madagascar.

PMID- 9172879
TI  - [The role of epidemiology in the process of decision-making].
AB  - Epidemiology is the method of choice for quantifying and interpreting health
      phenomena, placing them into perspective to allow trend analysis and projections.
      It is a tool for analysis, evaluation and forecasting and is thus indispensable
      in the decision-making process. However, this comprehensive technique has its
      limitations since health is the result of complex interactions: individual
      requirements do not always correspond to the overall needs of the community;
      consideration has to be given to solidarity and the necessity for cost-sharing;
      and the decision process is strongly influenced by social, cultural, religious
      and political factors which defy quantification and, on occasion, any rational
      course of action. Each indicator only takes into account one aspect of the
      situation and the pertinent indicator should therefore be carefully selected. At
      the same time, any choice implicitly signifies value judgements-often unnoticed
      which need to be balanced and validated in relation to the ethical values of the
      community in order to be of any assistance to decision-making. Decision-making is
      a qualitative political process which, although based on the quantitative
      analysis supplied by epidemiology, cannot be limited to it. Each approach enhance
      the other, but they should not be confused if freedom to act is to be preserved
      from being locked into some kind of mechanical process that is unacceptable both
      to man and to society.

PMID- 9172880
TI  - [Recent epidemiologic findings on hepatitis C virus].

PMID- 9172881
TI  - Lithium revisited.

PMID- 9172882
TI  - Lithium revisited.

PMID- 9172883
TI  - [Experience in training personnel for clinical diagnostic laboratories at a
      medical university].

PMID- 9172884
TI  - [The detection of microalbuminuria by using a recombinant albumin receptor].
AB  - Methods of ELISA competitive binding and blotting on nitrocellulose membranes
      were developed for detecting microalbuminuria in diabetic nephropathy. These
      methods are based on the use of recombinant albumin receptor. They are highly
      specific and sensitive and are recommended for everyday clinical use.

PMID- 9172885
TI  - [The potentials of immunological laboratory diagnosis].
AB  - Clinicians of different profiles often direct their patients to immunological
      tests because of a high incidence of various immunopathological syndromes, such
      as immunodeficiencies and allergic and autoimmune diseases. The efficacy of an
      immunological study depends on the task of the laboratory verification of the
      tentative clinical diagnosis, on the disease stage, and planned treatment.
      Biological material for investigation is collected depending on the task of the
      study and localization of the pathological process. It is not only the
      traditional material-blood, but other biological fluids of the organism as well.
      The choice of an adequate and informative complex of methods is also determined
      by the tasks of investigation. Special attention is paid now to methods for
      assessing the cytokine status of the organism. Interpretation of the results is
      the most intricate step of immunological tests because the notion of
      "immunological norm" is ambiguous and it is necessary to take account of the
      individual shifts of immunological parameters in the course of disease.

PMID- 9172886
TI  - [A method for determining thrombocyte intravascular activation and its
      significance for clinical practice].
AB  - The authors offer a visual method for assessing the intravascular platelet
      activation, based on examination under phase-contrast microscope of changes in
      the shape and relative number of blood platelets in aggregations. Results of
      examinations of patients with different thrombotic diseases are presented.

PMID- 9172887
TI  - [The diagnosis of paraproteinemic hemoblastoses].

PMID- 9172888
TI  - [Clinical laboratory diagnosis--its status and outlook. A scientific and
      practical conference. Saint Petersburg, 4-7 June 1996].

PMID- 9172889
TI  - [The senior laboratory assistant--the organizer of the work of a clinical
      diagnostic laboratory].

PMID- 9172890
TI  - [Information on a sectional meeting on the problems of cytological diagnosis].

PMID- 9172891
TI  - [2 decades of the work of the Centralized Clinical Diagnostic Laboratory of the
      I. M. Sechenov Moscow Medical Academy: traditional and nontraditional forms in
      analysing its activities].

PMID- 9172892
TI  - [The use of hematological analyzers in the clinic].

PMID- 9172893
TI  - [The accreditation of medical laboratories (the position of the experts of the
      European Confederation of Laboratory Medicine)].

PMID- 9172894
TI  - [The concept of a standard of quality in clinical laboratory studies].

PMID- 9172896
TI  - Update from the Ultrasonic Liposuction Task Force of the American Society for
      Dermatologic Surgery.

PMID- 9172895
TI  - [A method of sampling material for the determination of chlorides in sweat].

PMID- 9172897
TI  - Doesn't anyone remember the dangers of lead?

PMID- 9172898
TI  - [Etiology of diffuse scleroderma--proposal of a hypothesis and subsequent
      development].

PMID- 9172899
TI  - [Obligatory monitoring methods during delivery].
AB  - Fetal monitoring by cardiotocogram (CTG), fetal blood gas analysis (FBA) and
      pulse oximetry are mostly accepted by obstetricians. Other new methods are in
      discussion. Cost, benefit and need of the different methods are in continuous
      controversy. Successful screening by monitoring is focused on early detection and
      prevention of fetal asphyxia. Through the predictive value of fetal acidosis by
      CTG is only 30%, the cardiotocogram is the accepted standard method of fetal
      monitoring. In cases of difficult assessment of intrapartum CTG (4-6%) additional
      FBA is recommended. Perinatal statistics demonstrate no advantage of continuous
      monitoring. Intermittent electronic monitoring therefore is possible in
      deliveries without risk factors. The increasing rate of cesarean sections is
      followed by defensive medicine and not caused by fetal monitoring. Provided
      standards of fetal monitoring severe asphyxia in newborns with more than 1500 g
      is expected in 1:5,000 to 1:10,000 deliveries. The benefit of additional methods
      therefore seemed to be hardly to prove by prospective trials.

PMID- 9172900
TI  - [Lactate and glucose determination using biosensors in umbilical cord blood].
AB  - Postpartal determination of lactate and glucose in the umbilical cord whole blood
      of 139 successive deliveries utilizing biosensors (blood gas analysator 865, Ciba
      Corning) are presented. The median lactate value in the umbilical arterial blood
      is 4.45 mmol/l and in the venous blood 4.23 mmol/l. Following categorization into
      control and high-risk groups, the arterial mean values are 4.23 mmol/l and 6.39
      mmol/l and the respective venous values are 3.95 mmol/l and 5.04 mmol/l. Using
      the U-test these differences between the control and high-risk groups are
      significant. The mean of the measured lactate correlates significantly with the
      mean of the calculated base excess (< 0.001). The mean glucose value in the
      umbilical arterial blood is 78 mg/dl and in the venous 93 mg/dl. Between high
      risk and control group no significant difference is found.

PMID- 9172901
TI  - [Fetal fibronectin as a marker of prematurity in a high risk patient sample].
AB  - The accuracy of cervicovaginal fetal fibronectin as a predictor of preterm birth
      was studied in patients with increased risk for preterm delivery (according to
      the Creasy-score). In a prospective blind observational study the smear from the
      posterior fornix vaginae of 56 pregnant patients without PROM was examined using
      a quantitative immunoassay for the detection of fetal fibronectin. The patients
      who tested positively for fetal fibronectin had significantly more preterm
      deliveries than those with a negative result (CHI square-test, p < 0.01, RR 5.1).
      Overall, sensitivity, specificity, positive and negative predictive values were
      56%, 87%, 45% and 91%, respectively. In patients with preterm labor these values
      were 75%, 87%, 60%, and 93%, respectively. No patient with a negative result
      delivered preterm during the following two weeks. It is concluded that performing
      the fetal fibronectin test in patients with preterm labor is useful for the
      prediction of preterm birth. Routine testing in patients at increased risk
      (asymptomatic patients) is not recommended for lack of effectiveness.

PMID- 9172902
TI  - [Relaxin in amniotic fluid and serum of pregnant patients].
AB  - Relaxin was measured in serum and amniotic fluid of 136 pregnant women between
      the 12th and 38th gestational week by means of a new human relaxin-RIA. The
      pregnancies consisted of 111 pathology-free single fetuses, 10 with rhesus
      incompatibility, 7 with chromosomal aberration and 8 with sonographic diagnosed
      abnormalities. Relaxin could be detected in all samples tested the levels being
      ten times lower in amniotic fluid compared to serum. Serum relaxin levels showed
      a slight but not statistically significant decrease with increasing gestational
      age, in amniotic fluid relaxin values were consistent over the course of
      pregnancy. The ratio of amniotic fluid to serum relaxin displayed a statistically
      significant increase from the 12th to 23rd week of pregnancy. Individual courses
      of relaxin concentration in amniotic fluid revealed only low intra-individual
      variations but distinct inter-individual differences.

PMID- 9172904
TI  - [Fetal heart rate and acidosis].

PMID- 9172903
TI  - [Cause of death in pregnant women--with special reference to suicide].
AB  - Trauma is the leading cause of maternal death. Our cases included 8 x natural
      death, 4 x suicide, 2 x homicide, 2 x accident, 1 x heroin intoxication, 1 x
      medical malpractice. The calculated mortality ratio during pregnancy is only 1/20
      of the expected number. Pregnancy combined with single status, financial
      difficulties and interpersonal conflict are characteristic risk factors for
      suicide during pregnancy. In teenage pregnancy the risk for suicide seems to be
      higher than in pregnant women as a whole. Most suicides occur during the first
      trimester of pregnancy. Suicide during pregnancy is usually committed by tablet
      intoxication after interpersonal conflict. Drug abuse seems to influence suicidal
      behaviour.

PMID- 9172905
TI  - [Premature placental separation].

PMID- 9172906
TI  - [Heart rate accelerations in the fetus during fetal blood sampling sub partu].
AB  - Fetal heart rate acceleration is often observed when fetal blood sampling (FBS)
      is performed during labour. The aim of this study was to examine the influence of
      the occurrence of a fetal heart rate acceleration on the fetal condition
      immediately after the FBS incision during labour. 117 pregnant patients with a
      total of 210 FBS were included in the study. Particular attention was given as to
      whether an acceleration > or = 15 bpm and > or = 15 sec occurred immediately
      after the FBS incision. So 2 groups were formed: reactive (159 cases with
      acceleration) and non-reactive (51 cases without acceleration). No FBS
      acceleration was observed in any case with acidosis during labour. Therefore the
      occurrence of an FBS acceleration can be regarded as a reliable predictor of a
      fetal pH value of > or = 7.20 during labour. The test sensitivity amounts to 77%
      and the specificity and the positive predictive value are 100%. If an
      acceleration occurred immediately after the FBS incision, in 6% of the cases
      (negative predictive value) an acidosis with a pH value of < 7.20 was registered.
      The cesarean section rate increases by more than double from 13% to 33% when no
      FBS acceleration occurs.

PMID- 9172907
TI  - [Progressive degenerative aphasia: clinical and neuroradiological observations in
      18 cases].
AB  - INTRODUCTION: In some types of degenerative dementia aphasia is the main
      disorder. In primary progressive aphasia. (PPA) atrophy is limited to the
      dominant peri-sylvan region. We present 18 cases of progressive aphasia of
      degenerative origin, with or without dementia. MATERIAL AND METHODS: We describe
      the clinical and neuro-radiological findings in 3 patients with 'aphasic dementia
      and motor neuron disease (ADMND)', 7 with 'semantic dementia' (DS), and 4 with
      'fronto-temporal dementia' with 'marked non-fluent aphasia' (AFTD). Criteria
      published in recent years were used. RESULTS: In patients with ADMND non-fluent
      aphasia progressed to global aphasia, with dementia occurring after 2-9 months,
      and death after an average of 17 months. In cases with SD, initial anomic aphasia
      progressed to transcortical sensory or global aphasia, and in patients with AFTD,
      Broca's aphasia or motor transcortical aphasia progressed to global aphasia.
      Seven of these patients had been initially diagnosed as having PPA and became
      demented after two years or more. In most of the cases the cognitive disorder had
      the characteristics of fronto-temporal dementia. All cases had cortical atrophy
      or asymmetrical cortical or cortico-subcortical atrophy. The 4 cases of non
      fluent PPA were not demented after 21 months-6 years of illness, and showed
      perisylvan and left fronto-temporopolar atrophy. CONCLUSIONS: The PPA may
      correspond to the initial form of at least three varieties of dementia, usually
      the fronto-temporal type. Dementia occurs after two years or more, except in
      patients with motor neurone disease, when there is a latent period of less than
      one year.

PMID- 9172908
TI  - [Interaction between neuropsychological deficit in execution/ performance and
      ability to carry out daily activities in Alzheimer type dementia].
AB  - The objective of this paper is to establish whether the results obtained in a
      sample of 54 patients with alzheimer-type dementia, while carrying out different
      executive-praxia tasks is related to or influences the daily life and habits of
      these people, as analyzed on the Blessed dementia scale. The diagnosis of
      Alzheimer-type dementia was established on the criteria developed by the NINCDS
      ADRDA. Physical, neurological, neuropsychological, EEG and tomo-densitometric
      examinations were done in all cases. Executive-praxia function was analyzed on 5
      sub-scales; non-symbolic praxias, bucco-facial praxias, purposeless reflex
      praxias, reflex praxias with objects/instruments and praxias of ideas. There were
      significant differences depending on the praxias used. The more difficult tasks
      were evaluated by execution praxias involving ideational, non-symbolic executive
      praxias. The changes found on the subscale of activities of daily living were
      partly due to poor non-symbolic, ideatorial praxic execution and to a lesser
      extent to the poor results of the purposeless reflexive symbolic praxic execution
      and bucco-facial praxia. On the sub-scale of changes in habits, the non-symbolic
      praxias and ideatorial praxias explain the small percentage variation found on
      this sub-scale.

PMID- 9172909
TI  - [Grouped crises and status epilepticus in complex partial epilepsy].
AB  - INTRODUCTION: In complex partial crises (CPC) some characteristics of the way in
      which they occur may be helpful in localizing the focus of origin in the cerebral
      cortex. Thus, the appearance of any kind of status epilepticus will not
      predominate depending on the origin of the epileptic focus, but the complex
      partial state will be rare when the origin is temporal and more frequent when the
      origin is frontal. The appearance of CPC in a cluster form is, on the other hand,
      characteristic of crises originating in the frontal lobe. MATERIAL AND METHODS:
      We review the clinical history of 151 epileptics with CPC, evaluating the way in
      which the crises appear, together with other clinical data. We define the start
      of the crisis in a specific lobe, when this was the site of maximum voltage of
      the epileptic anomaly or of maximum phase opposition. RESULTS: 10% of the
      patients showed grouping of their CPC; in the remainder the appearance was
      isolated, 15% showed status epilepticus at some point in their illness. We found
      a statistical difference when relating this to the anomalous topography of the
      EEG; between 15% and 42% more patients with status epilepticus were counted when
      the topography of the anomaly in the EEG was extratemporal. There was also
      between 37.2% and 76.4% more patients with cluster crises in the cases with an
      extratemporal focus.

PMID- 9172910
TI  - [A new surgical treatment for syringomyelia, scoliosis, Arnold-Chiari
      malformation, kinking of the brainstem, odontoid recess, idiopathic basilar
      impression and platybasia].
AB  - INTRODUCTION: Based on medullary traction as responsible for idiopathic
      syringomyelia (SMI), idiopathic scoliosis (ESCID), Arnold Chiari malformation
      (ARCH), platybasia (PTB), basilar impression (IMB), odontoid recess (RTO) kinking
      of the brain stem (KTC) and considering the medullary traction to be transmitted
      by the filum terminale (FT), a surgical technique for the section of FT (SFT) is
      described in three cases of SMI, one of ESCID, and one of ARCH with no lumbar
      dysraphia. MATERIAL AND METHODS: A 34-year-old woman with cervico-brachialgias,
      paresthesias, bilateral babinski and a centro-medullary cavity C3-C7. A 26-year
      old male with cervico-brachialgias, hypoestesia in left hemybody, and
      cervicobulbar cavity. A 19-year-old female with ESCID since the age of 14th, with
      episodes of reacuting, and 38o of dorsolumbar curvature. A 67-year-old woman with
      intense headache, hypoesthesia of the hands, paraparesia and ARCH. A 23-year-old
      man with marked tetraparesia, bilateral babinski, anesthesia of both legs, SMI,
      ESCID, ARCH and hydrocephaly. RESULTS: After SFT: in the SMIs the thermo-algesic,
      disesthetic and algic dissociation disappeared. In ESCID there was a reduction to
      31o in the curvature in nine months. On ARCH the headaches ceased and there was
      recovery of touch and paraparesia. CONCLUSIONS: SFT is a useful etiological
      treatment for SMI, ESCID, ARCH. Also, in ESCID it is possible to avoid stress on
      the medulla due to its surgical reduction.

PMID- 9172911
TI  - [Botulinum toxin in spastic infantile cerebral palsy: results in 27 cases during
      one year].
AB  - INTRODUCTION AND OBJECTIVES: Positive outcome of patients with spastic cerebral
      palsy treated with botulinum toxin reported in the last three years has led us to
      perform this study with the aim to show our experience in the management of
      spastic cerebral palsy with the toxin, determine its indications, analyze the
      results and propose new possible indications in the future. MATERIAL AND METHODS:
      We include 10 hemiplegic and 17 diplegic patients with an average age of 6 years
      and 7 months, followed up between 5 and 17 months. Clinical improvement was
      monitored using the PRS and EVFEL scales and articular motion range was measured
      6 months before and after the injection while continuing physiotherapy. The
      injected muscles were adductor, hamstrings, triceps and posterior tibialis, and
      the doses were 1-2 U/muscle/kg body weight. RESULTS: The values on PRS improved
      an average of 24%, adductor angle 66% (p < 0.01), knee angle 40% (p = 0.05) and
      ankle angle 52% (p < 0.01); 96% of patients could get more physiological static
      or walking patterns because of the decrease of spasticity and those persisted
      after the effect of the toxin had worn off. It was maximum at 2 months,
      stabilized 4 to 6 months later and decreased during further 2 months.
      CONCLUSIONS: This experience leads us to propose higher starting dosage and to
      take into account the stability of postural pattern of each patient to choice the
      muscle to be injected. Other therapeutic possibilities are also proposed in
      children with fixed shortening e.g. combining the toxin with stretching casts.

PMID- 9172912
TI  - [Hormonal response to stress after cerebrovascular accident: relation to type,
      size and site of the lesion].
AB  - OBJECTIVE: To study the relationship between the hormone response to stress seen
      after ACV (CVA) and the type, size and site of the lesion. MATERIAL AND METHODS:
      We made a prospective study of the relationship between stress hormones and the
      radiological characteristics of the lesion in 82 patients admitted to hospital
      for non AIT ACV (CVA). We assessed the 24 hour urine catecholamines (total
      catecholamines, adrenaline, noradrenaline, vanillylmandelic acid, metanephrines
      and dopamine) and the 24 hour urine cortisol, collected on the second and third
      day after admission respectively. The type, size and site of the lesions were
      studies on CT scans done between 3 and 7 days after admission. RESULTS: We
      studied 82 patients, 43 men and 39 women with an average age of 71.7. In 7
      patients the lesion was parenchymatous haemorrhage; in 75 it was an infarct,
      which was small (< 6 cm3) in 30.5%, moderate sized (6-60 cm3) in 38.6% and large
      in 30.6%. In the cases of infarct, only the cortisol was significantly different
      in the three groups (average (DE) standard deviation, respectively: 80.6 (50),
      114 (124) and 246 (207); p = 0.0014). This relationship persisted when the
      cortisol level was compared with the volume in cm3 (p = 0.0028). The cortical
      infarcts had significantly higher levels of cortisol than the more deeply
      situated infarcts (83.2 (55) as compared to 174 (184); p = 0.0321), but the
      latter were smaller and no difference was seen when size was taken into account.
      All findings were similar in haemorrhages and infarcts of equal size.
      CONCLUSIONS: There was no relationship between the catecholamines and the type or
      size of the lesion. In our series, the site of the lesion did not appear to have
      any effect on the characteristics or intensity of the hormone response.

PMID- 9172913
TI  - [Secondary prevention of ischemic strokes: effect of dosage of aspirin].
AB  - INTRODUCTION AND OBJECTIVE: The value of acetylsalicylic acid (ASS) in the
      secondary prevention of ischemic stroke is well established. However, the optimum
      dose of AAS for stroke-threatened patients remains unsettled. This paper reviews
      the pattern of adverse reactions to AAS and their relationship to the dosage of
      ASS evaluated. METHOD: All the clinical trials in which AAS was used as the sole
      antiaggregant in the secondary prevention of ischemic stroke were reviewed. The
      crude odds ratio for the different adverse reactions was calculated using three
      sub tests: AAS versus placebo; AAS < 330 mg/d versus AAS > 330 mg/d; and each
      dosage level versus a placebo. RESULTS: There is an increased risk associated
      with the use of AAS as compared to a placebo with respect to gastrointestinal
      bleeding (OR 2.3, IC 95% (1.6-4.1)), peptic ulcer (10.1 (2.5-85.2)),
      intracerebral hemorrhage (2.2 (1.3-4)) and other hemorrhagic phenomena (2.6 (2
      3.3)). CONCLUSIONS: There seems to be a direct relationship between the dosage of
      AAS and the frequency with which adverse reactions occur, except in the case of
      intracerebral hemorrhage. In the latter case there was no relationship with the
      dose given (0.8 (0.5-1.4)).

PMID- 9172914
TI  - [Clinical significance of episodes of apnea in babies].
AB  - INTRODUCTION: The presence of episodes of apnea (EA) in infants is very alarming
      and requires rapid, precise determination of the etiology in view of the
      relationship with the syndrome of sudden death of infants. MATERIAL AND METHODS:
      We therefore studied 16 patients, aged between 1 and 12 months, admitted to to
      hospital after having episodes where they stopped breathing for more than 15
      seconds, with or without associated bradycardia. Patients with previous or
      associated convulsions, premature birth or low birth weight for gestational age
      were excluded from the study. In all cases a prolonged EEG was recorded. RESULTS:
      The commonest age of presentation of EA was 3-4 months. In one case there was a
      history of a sudden infant death occurring in a brother. The etiology was
      determined in 12 cases: gastroesophageal reflex in 5, epilepsy in 3, hyponatremia
      in 2, drug reaction in 1, bronchiolitis in 1 and hypoglycemia in another. In
      three cases where no cause was found the EA was not repeated, although apnea
      monitorization was necessary for several months because of the anxiety of the
      family. CONCLUSIONS: Of the 3 cases in which EA was a critical epileptic sign,
      only 2 could be demonstrated on a Holter recording. In one of these, progress was
      poor and resistant crises of different morphology later occurred. We consider
      that EA in infants requires a thorough etiological study. Cases of unknown
      etiology require prolonged EEG recording to determine whether the apnea is
      cerebral in origin, followed by prolonged monitorization of apneas to avoid
      possible sudden death.

PMID- 9172915
TI  - [Clinico-pathological correlation in the main types of dementia].
AB  - INTRODUCTION: Dementia has became a serious health problem in developed
      countries. The objective of this study was to establish the possible correlation
      between the initial clinical diagnosis and the anatomopathological criteria.
      Pathological confirmation of the cases clinically diagnosed as Alzheimer
      disease/senile dementia Alzheimer type (AD/SDAT) and multi-infarct dementia (MID)
      was carried out. MATERIAL AND METHODS: Twelve brains from demented patients were
      studied. Brains were removed at post-mortem intervals of 1-3 hours to guarantee
      an adequate conservation of the tissue. The brains were weighed, fixed for 4
      weeks in 10% buffered neutral formalin and coronally sectioned at intervals of
      approximately 1 cm. Bilateral sections of neocortex from frontal, temporal,
      parietal lobes, cingulate gyrus, amygdala, hippocampus, thalamus, cerebellum and
      unilateral sections of locus ceruleus and substantia nigra were taken. Five
      micrometer sections of the paraffin embedded material were stained by the
      following methods: hematoxylin-floxine, Congo red and Bielschowsky silver
      impregnation. RESULTS: Our neuropathological results showed a high correlation
      with the initial clinical classification and confirmed the diagnosis of AD/ SDAT
      in 6 cases, MID in 3 cases and mixed dementia in 1 case. Two cases did not
      exhibited morphological evidence of dementia. CONCLUSIONS: We concluded that the
      methodology applied for the morphologic diagnosis of dementia was feasible,
      useful and reproducible. Further studies will be necessary using a larger number
      of sample.

PMID- 9172916
TI  - [Primary cerebral lymphoma of T phenotype in an immunocompetent patient].
AB  - INTRODUCTION: Primary lymphoma of the central nervous system (PLCNS) makes up 1%
      of all intracranial tumours and 1% of all lymphomas [1]. It has been described in
      different types of immunodeficiencies, but in recent years has been increasingly
      found in immunocompetent persons. The LPSNC are usually B cell tumours, so the T
      phenotype is yet another rare aspect. CLINICAL CASE: A 62-year-old man, smoker,
      BCO, presented with a clinical picture (for the previous month and a half) of
      holocranial headache, positive Valsalva manoeuvre, unsteadiness, tendence to
      retropulsion and difficulty in starting to walk. On physical examination there
      was deficient orientation in time and space, slight dysarthria, regressive
      reflexes and ataxia on walking. Cerebral CT scan and MR scans showed
      periventricular, thalamic and mesencephalic lesions with behaviour suggestive of
      a lymphoma. Neoplasia was confirmed on biopsy. Three months later, whilst on
      corticotherapy and holocranial radiotherapy, the patient died from intercurrent
      infection. CONCLUSIONS: To date, including the present case, 51 cases of T
      lymphoma have been described in immunocompetent patients. Our case showed aspects
      described in the literature. These were: more often made [2], more often
      infratentorial [2-4] and of poor prognosis with regard to the degree of
      histological malignancy [5].

PMID- 9172917
TI  - [Motor neuron disease and HIV].
AB  - Motor-neuron disease, in particular its commonest form (lateral amyotrophic
      sclerosis) is a degenerative disease of unknown aetiology and inexorable course
      with an estimated incidence of 0.4-1.8 per 100,000 inhabitants. In recent years
      great efforts have been made to discover the aetiopathogenesis of this disorder,
      studying genetic, viral, endocrine, toxic factors, etc. We present the case of a
      30 year old man who started to develop a clinical condition compatible with motor
      neuron disease 18 months after diagnosis of HIV. An extensive differential
      diagnosis was considered in view of this past history. Complementary tests
      considered necessary for diagnosis of motor-neurone disease and for exclusion of
      other neurological conditions related to HIV were done. After 16 months of follow
      up the condition has become a clear case of ELA type motor neurone disease with
      no further HIV-related pathology. We discuss questions concerning the
      aetiopathology of the disease, based on the currently accepted viral hypothesis
      and describe recent findings related to both.

PMID- 9172918
TI  - [Complete axonotmesis of the axillary nerve in relation to microtrauma].
AB  - INTRODUCTION: The axillary nerve is injured in many clinical situations, mainly
      in major surgical or traumatic lesions of the shoulder. Equally, it may be found
      in the context of microtraumatisms or compressive mechanisms. Amyotrophic
      neuralgia is a clinical entity with pain and later atrophy of the muscle which
      affects various nerves and nerve groups, as shown by neurophysiological studies.
      CASE REPORT: We present a lesion with complete axonotmesis of the axillary nerve
      with a time-relationship to microtraumatism. Initially the patient complained of
      some pain in the shoulder. During follow-up striking atrophy of the deltoid
      muscle was seen. CONCLUSIONS: We have reviewed the mechanisms described for
      lesions of the axillary nerve, which do not include the one we found. We discuss
      the possibility of our case being included in the clinical group described as
      having amyotrophic neuralgia, although there are some neurophysiological findings
      which are not typical of this condition. We suggest a review of the many possible
      trigger factors described in the genesis of amyotrophic neuralgia. Possibly some
      cases with atypical histories of trauma, and lesions shown by neurophysiological
      studies to be particularly severe, may be separated from this group.

PMID- 9172919
TI  - [HTLV-I myelopathy: presentation of a new case].
AB  - INTRODUCTION: HTLV-I is a human retrovirus which has been implicated in the
      genesis of tropical spastic paraparesis (HTLV-I-associated myelopathy). So far
      five cases of this illness have been detected in Spain, five of them in
      immigrants. We present a new case in Spain, with a characteristic chronic
      clinical picture. CASE REPORT: A 36-year-old black woman native of Ecuatorial
      Guinea, developed along 10 years a progressive paraparesis of asymmetric onset
      with important back pain, that arrives to paraplegic spastic phase at the present
      time. She presents distal amyotrophies, ulcers of decubitus and loss of control
      of sphincters, with normal mental status. Laboratory tests: blood, biochemistry
      and microbiologic studies: normal, or negative. She presented positive Western
      Blot serology for HTLV-I, confirmed by means of PCR technique. Cranial MRI: small
      and hyperintense subcortical lesions on T2 weighted images; spinal MRI: local
      atrophy at high thoracic level. A lumbar puncture was performed, with no cells,
      and with presence of oligoclonal bands, and a high IgG index. Urodynamic study:
      neurogenic spastic bladder. EMG: mild axonal polyneuropathy with prevalence in
      legs. CONCLUSIONS: In the differential diagnosis of progressive paraperesis, and
      mainly with epidemic antecedents, it is necessary to include a determination of
      HTLV-I between the diagnostic tests.

PMID- 9172920
TI  - [Familial multiple cavernomatosis].
AB  - We present a family study of multiple cavernomatosis which affected a boy of six,
      his mother and two brothers. It was seen clinically as epileptic crises, focal
      neurological defects and frequent headaches. In our case, the condition started
      as a syndrome of intracranial hypertension with progressive headache and
      vomiting. During the illness, localizing neurological signs due to bleeding were
      seen. Amongst these were acute left hemiparesia and paralysis of vertical gaze.
      Other members of the family remain symptom-free. In a search for angiomas at
      other sites none were found in the patient or his family. Recently the gene
      giving rise to the familial cerebral cavernosa malformation has been found to be
      a locus on chromosome 7. We discuss the findings on neuro-imaging, emphasizing
      the importance of magnetic resonance (MR) both in diagnosis and finding affected
      asymptomatic family members, because of its great sensitivity and specificity.
      Angiography is not a suitable technique for this since they behave as hidden
      malformations. We also point out its importance as a way of following-up the
      illness and for evaluation of possible complications due to progressive growth or
      sudden haemorrhage, which may indicate the need for treatment. Finally we
      emphasize the different characteristics of MR signals in this type of lesion
      since cavernomatasa malformations are dynamic lesions.

PMID- 9172921
TI  - [Aphasia in a polyglot: description and neuropsychological course].
AB  - We present a case of aphasia due to an ischaemic lesion in the left temporo
      occipital region of the brain of a 60 year old right-handed polyglot. Mother
      tongues: French, Italian, Arabic. Educated at school in English. Languages learnt
      as an adult: German, Portuguese, Spanish. Language habitually spoken prior to
      illness: Spanish. His language disorder was of non-fluent type and progressed to
      an anomic disorder. The non-parallel recovery of languages led to an initial and
      predominant recovery of English (language at school) followed by French (his
      first language). This type of non-parallel recovery may be compatible with the
      inhibition-disinhibition mechanism hypothesis. This would mean that the languages
      of least recovery are inhibited by raising the threshold of some circuits while
      still permitting comprehension.

PMID- 9172922
TI  - [Poems syndrome: a case report].
AB  - INTRODUCTION: The Poems syndrome (polyneuropathy, organomegaly, endocrinopathy,
      monoclonal gammapathy and skin changes) is an uncommon multisystemic disorder.
      Usually it is a manifestation of a type of myeloma of which the chief
      characteristic is the presence of osteosclerotic lesions, classically seen
      radiologically to be single or multiple. Nowadays, not only is Poems considered
      to be a manifestation of osteosclerotic myeloma, but may also be seen associated
      with other plasma cell dyscrasias. CLINICAL CASE: We present a case of Poems
      syndrome secondary to a plasmocytoma of the dorsal vertebral column in a 32 year
      old male negro. Initially he had sensori-motor polyneuropathy associated with
      other features characteristic of the syndrome (organomegaly, IgA monoclonal
      gammapathy and skin changes). Later he also showed signs attributed to a
      compressive lesion of the dorsal spinal medulla. An unusual finding in this
      patient was that the bony lesion was predominantly osteoclytic. CONCLUSIONS: We
      briefly review the syndrome and comment on the diagnosis.

PMID- 9172923
TI  - [Cerebral venous thrombosis].
AB  - INTRODUCTION: Cerebral venous thrombosis (CVT) is a type of pathology which has
      many predisposing factors and forms of presentation, which make diagnosis and
      prognosis difficult. The objective of this paper is to review, and bring up to
      date, different aspects of knowledge concerning: aetiology, clinical features,
      diagnosis and treatment. MAIN FINDINGS: The proportion of cases of unknown
      aetiology is between 20-35% in spite of new causes being described. Magnetic
      resonance and recently, angiographic resonance are the diagnostic methods of
      choice, although conventional angiography is still necessary in some cases. The
      treatment of CVT is based on correction of the cause, control of symptoms and the
      use of anti-thrombotic drugs, mainly anticoagulants and more recently,
      fibrinolytic agents. The mortality of current series of patients is 10-15% and
      only 15-25% of the patients show sequelae. CONCLUSIONS: CVT is not rare and neuro
      imaging techniques allow early diagnosis of more cases. In general prognosis is
      good. Antithrombotic treatment is still controversial and further study is
      necessary in this field.

PMID- 9172924
TI  - [Mini-mental state examination: proposal of protocol to be used].
AB  - The Mini-Mental State Examination (MMSE) is currently one of the most widely used
      tools for the assessment and screening of cognitive impairment despite a number
      of issues raised regarding the sensitivity of some subtests and the negative
      impact of advanced age and poor education. The informal use of invalidated and
      poor quality translations of the MMSE into Spanish language is widespread, and
      presumably this further increases some of the uncertainties linked to this test.
      The result may be misleading, not only as it may overestimate the prevalence of
      dementia but because it decreases interrater consistency with a view to
      epidemiological projects. A validated translation of the MMSE into Spanish is
      therefore much needed. Such a version would not only pay attention to educational
      and age issues but it would also take into account potential cultural and
      linguistics inter-community difference of some subtests when specifically applied
      in Spain which may represent another potential source of inconsistency throughout
      the country. Furthermore, subtle inhomogeneities in the way the test is
      administered may result in gross intra-rater and inter-rater variability, hence
      further decreasing reliability. On the basis of experience gained from a large
      hospital-based experience in administering the traditional MMSE to neurological
      patients we propose a standardized version to apply MMSE in Spanish with the alm
      to improve reliability. This is a preliminary step toward developing a reliable
      and sensitive Spanish version of the MMSE.

PMID- 9172925
TI  - [Mesial temporal sclerosis (I): histological data, physiopathological hypothesis
      and etiological factors].
AB  - OBJECTIVE: To review the main anatomical, histological, physiopathological and
      aetiological data characteristic of the mesial temporal sclerosis syndrome (ETM).
      Development. The typical histological findings in ETM are: 1) A specific pattern
      of loss of neurone density which includes so-called endfolium sclerosis
      (considered to be a specific pathological entity always found in ETM), and which
      is usually accompanied by neurone loss in other hippocampal and extra-hippocampal
      regions. The CA2 region is never affected. 2) Phenomenon of 'mossy fibers
      sprouting' which are granulosa cells which form two types of synapses: with the
      the 'basket cells' which are inhibitory interneurones and with the dendrites of
      granulosa or pyramidal cells of the CA1, CA2 and CA3 Ammon horn cells which are
      excitatory cells. CONCLUSIONS: Probably these organic changes are both the cause
      and effect of repeated convulsions. Participation in this self-perpetuating
      circuit may be due to recognised risk factors of ETM (head injury, CNS
      infections, febrile convulsions in early stages of development) which cause,
      first of all, death of neurones of the dentate gyrus cells followed by reduced
      inhibitory activity of the 'basket' cells and therefore sustained hyper
      excitability of the pyramidal cells (especially in the CA3 regions), which are
      responsible for complex partial seizures and massive liberation of glutamic acid.
      Glutamic acid can cause death of neurones of the granulosa cells of the dentate
      gyrus, thus closing the circuit. This hypothesis explains the progressive nature
      of the ETM syndrome. When there is pathology of the cortical structure there is
      another access via to this circuit--by means of cortical discharges of the so
      called perforant pathway which stimulates activity of the pyramidal cells and
      sets off the chain of events described above. This hypothesis explains the so
      called 'dual pathology'.

PMID- 9172926
TI  - [Dietetic treatment of epilepsy].

PMID- 9172927
TI  - [Emancipation, both legal and from care, of the epileptic patient and other
      neuropsychiatric patients during the Restoration].

PMID- 9172928
TI  - [Tissue microdialysis: practical and theoretical aspects].
AB  - Microdialysis is now widely used for the study of peripheral tissues. This
      technique allows the monitoring of metabolites and small molecules from the
      extracellular compartment as well as local delivery of metabolically active
      agents to this compartment. The purpose of this review was to present a practical
      approach (different types of probes, molecular cut-off, perfusion rate, dialysis
      buffer) and discuss the theoretical aspects of in vivo microdialysis (probe
      efficiency, recovery, perfusion rate, quantification of tissular metabolism). Our
      goal was to provide researchers with the practical tools needed for rapid mastery
      of in vivo tissular microdialysis.

PMID- 9172929
TI  - [Psychological changes observed in parents when the diagnosis of insulin
      dependent diabetes in their child is announced].

PMID- 9172930
TI  - ["Diastology"].

PMID- 9172932
TI  - [Study of the interatrial septum using transthoracic echocardiography].

PMID- 9172931
TI  - [Mediterranean anemia and the cardiovascular system].

PMID- 9172933
TI  - [Clinical implications derived from arterial hypertension models].

PMID- 9172934
TI  - [Does a genetic predisposition for infarction expansion exist? Evaluation of
      genetic polymorphisms of the renin-angiotensin system].
AB  - Aim of this study is to carry out a genetic analysis of polymorphisms of the
      renin-angiotensin system in a genetically homogeneous population, in patients
      with and without myocardial infarction (AMI) expansion and to evaluate the
      influence of non genetic, mechanical factors. The study was conducted on 299
      patients with first AMI. Ecocardiography studies were performed on all patients
      on day 1 and 3 from the onset of AMI and before discharge. Eighty-four patients
      were excluded because of inadequate quality of echocardiograms and 215 (163
      males, 52 females) were admitted. Of these, 157 had no evidence of AMI expansion
      (EXP-) while 58 had expansion (EXP+). DNA was extracted by standard methods from
      blood samples. Age and gender had no influence on AMI expansion. Anterior
      infarction (p < 0.000001) and Q-wave infarction (p < 0.00002) were found more
      frequently in EXP+. Peak of creatine phosphokinase was higher in EXP+ than in EXP
      (p < 0.00001). The percent of patients treated with thrombolysis or with
      hypertension and/or left ventricular hypertrophy was not significantly different
      in the two groups. AGT MT235 polymorphism of angiotensinogen gene, I/D
      polymorphism of ACE gene and AT1 A1166C of AT1 receptor of angiotensin II were
      not significantly different in two groups. Stratified analysis showed that in
      patients with anterior AMI (n = 87), with a higher risk of AMI expansion, there
      is a significant difference (p < 0.02) in ACE genotype between EXP- and EXP+.
      Odds ratio assuming the dominant effect of I allele (II+ ID < DD) was 3.35
      (confidence interval 1.41-7.56) with increased risk of expansion. More extension
      studies are need to verify if these results can contribute to early
      identification of patients at higher risk and to optimize therapeutic approach.

PMID- 9172935
TI  - [Significance of hypotension and vasovagal reflex during echo-stress using high
      doses of dobutamine].
AB  - Coronary artery disease (CAD) is one of the main causes of cardiovascular
      morbility and mortality. Actual research lines are directed towards the discovery
      of silent CAD before hard events as myocardial infarction and sudden death.
      Dobutamine stress echocardiography is an useful method to assess patients with
      suspected CAD who, are not able to stand an effort because of physical reasons.
      During the test, hypotension and/or bradycardia may occur and may cause
      interruption of the test. The aim of our study was to consider prevalence,
      meaning and clinical implications of hypotensive, sometimes associated to
      bradycardia, during dobutamine stress echocardiography. From April 1994 to June
      1996, 363 consecutive patients (267 men and 96 women with an average age of 59.3
      +/- 10 year) were examined because of suspected or known ischemic cardiopathy.
      All patients underwent dobutamine stress echocardiography and coronary
      arteriography. Neither hypotension nor bradycardia was noted in 285 of our
      patients (78.51%), while in the remaining 78 patients (21.48%) there was a
      pressure drop > or = 20 mmHg; bradycardia appeared in 6 patients. The study shows
      that it does not exist a statistically significant difference between the
      percentage of the patients with CAD of the control group and those of the
      hypotensive group (91.9 vs 83.3%, NS). As for the changes in well motion score
      index, there was not a statistically significant difference between patients
      improved score index in the control group and in the hypotensive group (80 vs
      74.3%, NS). The 6 patients with hypotension and bradycardia had normal coronary
      arteries. In the light of these results hypotension, alone or associated with
      bradycardia, should not be considered as a negative prognostic factor and should
      not induce to the interruption of the dobutamine stress echocardiography.

PMID- 9172936
TI  - [Diagnosis of coronary disease using multiplane transesophageal echocardiography
      and atrial pacing].
AB  - The diagnostic value of echo-pacing has been previously report. Recently,
      monoplanar transesophageal echocardiography (TEE) has been used to improve the
      reliability of this stress procedure. Therefore, in 40 consecutive patients
      undergoing coronary angiography for suspected coronary artery disease (CAD) we
      tested the accuracy of atrial pacing (TAP) during multiplane TEE as a stress
      procedure. TAP was performed during TEE using a circular, adhesive electrode
      installed at the tip of the echoscope and connected to the pulse generator. In
      all patients TAP was firstly attempted by positioning the TEE probe in the
      esophagus and, if not successful, in the stomach. Left ventricular wall motion
      was monitored by means of 4, 2 chamber and long axis views from the esophagus and
      short axis scan from the stomach, in baseline conditions, at peak pacing and
      immediately after maximal heart rate. The test was considered positive if wall
      motion abnormalities developed during TAP. Stable capture of the atrium was
      obtained in 28 patients from the esophagus and in 6 patients from the stomach.
      Thus, TEE-TAP was performed in 34/40 patients (feasibility 85%). Wall motion
      abnormalities were detected during TAP in 20/24 with and in 2/10 patients without
      CAD. Thus, sensitivity and specificity of TEE-TAP were 83% and 80% respectively.
      The sensitivity of the test in single and multivessel disease resulted 72% and
      92%. The 12 lead electrocardiogram during TAP showed a sensitivity of 66% and a
      specificity of 40% (p < 0.01 vs TEE-TAP). In conclusion, TEE-TAP is a new
      approach for CAD evaluation providing a complete and accurate imaging of left
      ventricular wall motion.

PMID- 9172937
TI  - [Complete congenital atrioventricular block: a case report and review of the
      literature].
AB  - The description of a clinical case of a newborn with congenital complete
      atrioventricular block, due to maternal connective-tissue disease, is the
      occasion for a review of the literature. The clinical elements allowing an early
      diagnosis and treatment of these patients, who often need a permanent pacemaker,
      are described.

PMID- 9172938
TI  - [Ultrafast computerized tomography: cardiovascular applications].

PMID- 9172939
TI  - [Correction of interatrial defect of the ostium secundum type].

PMID- 9172941
TI  - [Health status of adolescents: what relations with family image? Adolescents Work
      Group].
AB  - INTRODUCTION: Many studies have been carried out recently to investigate the
      relationship between health conditions and family and self characteristics.
      OBJECTIVES: To identify family characteristics (such as type of family, socio
      economic status, parent immigration, affection for parents, parents'
      psychological and physical health) and self characteristics (age, drug use,
      satisfaction for several life circumstances, psychosomatic symptomatology) that
      are differently distributed by sex and levels of psychological and physical
      distress among teen-agers. METHODS: We carried out a cross-sectional study on a
      sample of teen-agers attending high school in Pavia (Italy), using a self
      administered questionnaire. The students were divided in four groups having
      different levels of psychological and physical distress, based on GHQ-30
      (psychological distress indicator), on the number of hospital admissions and
      consultations to a physician in the last year (the last two are physical distress
      indicator). Data were analysed applying the multivariate analysis of Canonical
      Variate. RESULTS: 1346 students were sampled, but only 1189 questionnaire were
      analysed: 36.8% regarding males and 63.2% females. The Canonical Variate analysis
      indicated that psychosomatic symptomatology, satisfaction for several life
      circumstances and affection for parents are important for describing the four
      distress groups. CONCLUSIONS: Only affection for parents has an important role on
      psychological and physical distress of adolescents, while family characteristics
      traditionally considered associated with psychological and physical distress in
      teen-agers (such as living with one or without parents, low socio-economic
      status) are not associated.

PMID- 9172940
TI  - [Variability of managerial and clinical decisions in mental health services of
      the Lombardy Region: the vignette method].
AB  - This paper concerns one of the four research projects developed during a training
      course in clinical epidemiology managed by the Lombardy training centers IREF.
      OBJECTIVES: To compare the recommendations for treatment concerning 9 vignettes
      derived from the Australian Quality Assurance Project. SETTING: Six Mental Health
      Services of Regione Lombardia. DESIGN AND PARTICIPANTS: For each vignette, all
      psychiatrists working in the 6 Mental Health Services were asked to fill in a
      questionnaire about treatment location, psychopharmacology, psychotherapy,
      priority between psychotherapy and psychopharmacology and degree of difficulty in
      answering. RESULTS: 44 out of 52 target psychiatrists took part to the study.
      Remarkable variability for treatment location and psychotherapies; moderate
      variation for psychodrugs prescriptions and a good agreement for diagnoses were
      observed. In drugs prescription an access of association was observed. The most
      prevalent model of psychotherapy was the psychodynamic, followed by the cognitive
      behavioural and the family-systemic. There was a tendency toward a flexible
      approach, as suggested by recommendations of different psychotherapeutic models
      according to the nature of the disorder. No case were judged very difficult; only
      in 3 cases a judgement of "somewhat difficult" was expressed by more than 20%
      (but less than 30%) of the psychiatrists. CONCLUSIONS: Studies of this type are
      very easy to carry out and give useful information for continuous training
      programs and Continuous Quality Improvement projects.

PMID- 9172943
TI  - Characterization of the metabolites of carbamazepine in patient urine by liquid
      chromatography/mass spectrometry.
AB  - The urinary metabolites of carbamazepine (CBZ) in epileptic patients receiving
      long-term drug treatment have been characterized by LC/MS. CBZ-10,11-epoxide (9.6
      15.0 micrograms/ml), trans-10, 11-dihydrodiol-CBZ (273.0-400.00 micrograms/ml),
      and CBZ (2.4-3.8 micrograms/ml) were measured by HPLC. The secondary N
      glucuronide of CBZ, four phenolic O-glucuronides (including those of 2- and 3-OH
      CBZ), two additional OH-CBZ O-glucuronides, and the N-glucuronide of CBZ-10,11
      epoxide constituted the products of either direct conjugation or preliminary
      monoxygenation. Derivatives of these monoxygenated compounds, which were
      characterized as O-glucuronides, were represented by dihydroxylated (catechol)
      CBZ and its putative O-methyl metabolite and by 10,11-dihydrodiol-CBZ. 10,11
      Dihydro-10-OH-CBZ O-glucuronide, a metabolite thought to be excreted only by
      uremic subjects, was not found. More complicated biotransformations of the 10,11
      ene moiety were revealed by two carbinol products of azepine ring contraction: 9
      OH-methyl-10-carbamoyl acridan and an hydroxylated derivative thereof, which were
      excreted as O-glucuronides. No polar sulfur-containing metabolites that might
      serve as indicators of reactive intermediate formation were found in human urine.

PMID- 9172942
TI  - [Request for psychiatric admission: data from eight general hospital psychiatric
      wards in Lombardy].
AB  - OBJECTIVE: To describe requests of admissions to eight General Hospital
      Psychiatric Wards (SPDC) in Lombardy, Italy, during November 1995. DESIGN:
      Descriptive prospective multicenter study. SETTING: SPDCs of Busto Arsizio (VA),
      Calcinate (BG), Desio (MI), Magenta (MI), Merate (LC), Milano San Paolo I, Pavia,
      Treviglio (BG). The global catchment area sums up to 11% of the whole regional
      area, and to 18% of the population. MAIN OUTCOME MEASURES: We used a previously
      developed flow chart with two major key points: who decided to go to the
      hospital? Did a doctor confirm this initiative? Main sociodemographic
      characteristics, ICD10 diagnosis and previous psychiatric admissions were
      collected for each admission. RESULTS: Admissions were 315, patients 246. In 9.5%
      of cases patients asked for admission without any medical advice. In one third of
      cases the ward psychiatrist was the first doctor to visit the patient. Compulsive
      admissions (TSO) were 45 (14.3%), although patient's initiative lacked in 55.6%
      of cases. A referral from Outpatient Departments (CPS) was present in 28.2%.
      First-ever admitted were 63 (25.6%): 20.7% sent by CPS, 16% by GPs, 11% by other
      non psychiatric wards. CONCLUSIONS: Although Goldberg & Huxley's model described
      General Hospital Psychiatric Wards as the last level of intervention, our data
      show that Italian SPDCs work as "front lines" services: less than one admission
      out of two were referred by a psychiatrist. Problems raised by "self-referred"
      patients are conspicuous and an evaluation of the filtering function of CPSs
      seems necessary. In this regard, a comparison with different modalities of
      Department organization could be useful.

PMID- 9172944
TI  - Enantioselective local disposition of semotiadil (R-enantiomer) and
      levosemotiadil (S-enantiomer) in perfused rat liver.
AB  - The enantioselective local disposition of semotiadil (R-enantiomer) and
      levosemotiadil (S-enantiomer) in rat liver was investigated in the single-pass
      perfusion system containing 1% bovine serum albumin (BSA). After an instantaneous
      injection of semotiadil, levosemotiadil, or Evans Blue (a marker of BSA), each
      outflow time profile from the liver was analyzed by a two-compartment dispersion
      model. The recovery ratio, FH (1.88 +/- 0.28%), of semotiadil was significantly
      smaller than that (8.99 +/- 1.40%) of levosemotiadil. The mean transit time, fH
      (0.146 +/- 0.014 min) of semotiadil was significantly smaller than that (0.191 +/
      0.012 min) of levosemotiadil. The biliary excretion kinetics of these
      enantiomers was also evaluated by moment analysis. The parent compound
      (semotiadil or levosemotiadil) was not detected in bile, but four metabolites
      generated from each parent enantiomer were found in the bile. A portion (16.5 +/-
      1.2%) of the drug eliminated by the liver was recovered as R-metabolites in the
      bile within 1 hr after an injection of semotiadil, whereas 11.2 +/- 1.6% was
      recovered as S-metabolites in the bile within 1 hr after an injection of
      levosemotiadil. This excreted percentage into the bile was significantly
      different between R- and S-metabolites. The mean biliary excretion time MRTe
      (19.1 +/- 2.2 min) of total R-metabolites was significantly larger than that
      (14.8 +/- 1.1 min) of total S-metabolites. In conclusion, stereo-selectivity was
      suggested both at the hepatic elimination of the parent compound and at the
      biliary excretion of the metabolites.

PMID- 9172945
TI  - Inhibition of metoprolol metabolism by amino acids in perfused rat livers.
      Insights into the food effect?
AB  - A mixture of amino acids inhibits propranolol metabolism in perfused rat livers.
      To obtain mechanistic information about the interaction, a related but less
      tissue-bound drug, metoprolol, was used to determine Vmax and K(M) for parent
      drug and two metabolites in the presence and absence of amino acids. Six groups
      of 4 livers from 24 male Sprague-Dawley rats were perfused in the single-pass
      mode at 3 ml/min/g liver for 130 min with oxygenated buffer containing 3.74,
      4.49, 5.61, 7.48, 18.7, or 44.9 microM metoprolol. From 50 to 90 min, a balanced
      amino acid mixture was included in the buffer. Samples of liver effluent taken
      every 5 min were analyzed by HPLC for metoprolol and two metabolites, alpha
      hydroxymetoprolol and O-demethylmetoprolol. Steady-state concentrations of drug
      determined before, during, and after amino acids were used to determine Vmax and
      apparent K(M) values by nonlinear curve-fitting under each condition. Amino acids
      reversibly reduced the Vmax values of metoprolol and both metabolites by
      approximately 50% without significantly affecting apparent K(M) values. As a
      result, large increases in availability occurred, especially at low metoprolol
      inlet concentrations (> 90%). Amino acids also increased oxygen consumption until
      the effluent buffer was almost depleted. Possible mechanisms influencing Vmax
      include direct inhibition of metabolic enzymes by amino acids or cosubstrate
      (NADPH or oxygen) limitation. Amino acid-mediated pericentral oxygen depletion in
      the hepatic sinusoids could result in inhibition of drug-metabolizing enzymes,
      and is consistent with a reduction of Vmax and oxygen depletion in the effluent
      buffer during amino acid coinfusion. We postulate that one or more of these
      mechanisms could contribute to the interaction between food and high first-pass
      drugs observed in humans.

PMID- 9172946
TI  - Effect of phenobarbital on the pharmacokinetics of lidocaine,
      monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450
      isoform levels.
AB  - To elucidate the effect of cytochrome P450 levels in hepatic microsomes on the
      metabolism of lidocaine in vivo, we investigated the metabolism of lidocaine in
      untreated (UT group) and phenobarbital-treated rats (PB group) in vivo and
      compared the results with those obtained by immunoblotting of rat hepatic
      microsomes. There were no differences in pharmacokinetic parameters for lidocaine
      between the UT and PB groups. The plasma concentrations of the N-deethylated
      metabolite of lidocaine, monoethyl-glycinexylidide (MEGX), in the PB group were
      significantly higher than those in the UT group. On the other hand, the plasma
      concentrations of the aromatic ring hydroxylated metabolite of lidocaine, 3
      hydroxylidocaine (3-OH LID), were significantly lower in the PB group than in the
      UT group. When lidocaine metabolism was studied with hepatic microsomes prepared
      from rats in the UT and PB groups, the rates of formation of MEGX were higher in
      the microsomes of the PB group than in those of the UT group. The contents of
      CYP2B1 and 3A2 in rat hepatic microsomes of the BP group measured by
      immunoblotting were significantly higher than those of the UT group. Strong
      correlations were found between the area under the plasma concentration vs. time
      curve for MEGX and specific contents of CYP2B1 and 3A2. These findings suggest
      that formation of MEGX in vivo is dependent on the levels of CYP2B1 or 3A2 in rat
      liver.

PMID- 9172947
TI  - Microbial models of mammalian metabolism. Fungal metabolism of phenolic and
      nonphenolic p-cymene-related drugs and prodrugs. I. Metabolites of thymoxamine.
AB  - This study was undertaken to validate the use of microbial biotransformation
      systems for drug metabolism studies. Thymoxamine 1 was rapidly hydrolyzed to
      desacetylthymoxamine (DAT) 2 by numerous fungi. Other known animal metabolites,
      such as N-desmethyl-desacetylthymoxamine 3 and desacetylthymoxamine-O-sulfate 6,
      were produced from DAT by Mucor rouxii and Mortierella isabellina. DAT-N-oxide 5,
      a putative animal microsomal metabolite, was also produced by M. isabellina, in
      addition, a few strains (such as Actinomucor elegans, Mucor hiemalis, and Mucor
      janssenii) produced a glycosylated metabolite that was identified by high
      resolution 1H- and 13C-NMR, MS, and enzymatic hydrolysis as the corresponding [4
      (2-dimethylaminoethoxy)-5-isopropyl-2-methyl-phenyl]-1-beta-D- glucopyranoside 7.
      A similar glucosylation reaction was observed when thymohydroquinone 10 was
      incubated with A. elegans. Several strains were able to produce transiently
      thymohydroquinone from DAT-N-oxide 5, possibly through a beta-elimination
      mechanism.

PMID- 9172948
TI  - Microbial models of mammalian metabolism. Fungal metabolism of phenolic and
      nonphenolic p-cymene-related drugs and prodrugs. II. Metabolites of nonphenolic
      derivatives.
AB  - A cymene-derived drug, 3-[4'-(o-ethoxyphenyl)piperazin-1'-yl]-ethyloxy-p-cymene+
      ++ (B1178), is not significantly metabolized by fungal microorganisms. On the
      contrary, one of its metabolites in rat, 3-(piperazin-1'-yl)ethoxy-p-cymene
      (B1071), is quantitatively converted by Cunninghamella echinulata NRRL 3655 into
      two hydroxylated products: the corresponding phenol derivative and a benzylic
      alcohol derivative. Other strains, such as Beauveria bassiana ATCC 7159 and
      Mortierella isabellina MMP 108, produce exclusively an N-acetyl derivative in
      high yield. Results obtained are discussed on the grounds of relative
      hydrophobicity of substrates vs. fungi metabolism and detoxification
      capabilities.

PMID- 9172949
TI  - Residue study of mebendazole and its metabolites hydroxy-mebendazole and amino
      mebendazole in eel (Anguilla anguilla) after bath treatment.
AB  - Mebendazole (MBZ) is extensively used in eel culture for treatment of
      Pseudodactylogyrus spp. infections. This use may lead to residues of MBZ in eel
      tissues. Consequently, the residue profile of MBZ in eel after treatment with the
      drug is of special concern. Therefore, a residue study was performed in European
      eels (Anguilla anguilla), bath-treated with MBZ at a dose of 1 mg/liter for 24 hr
      and kept at a water temperature of 25 degrees C. Liver, kidney, fat, skin, and
      muscle tissues samples were collected at intervals during and after treatment and
      analyzed for MBZ and its metabolites, hydroxy-MBZ (MBZ-OH) and amino-MBZ (MBZ
      NH2), by HPLC. Results showed that MBZ is extensively metabolized to MBZ-OH and
      MBZ-NH2. Liver and kidney were found to contain the highest levels of MBZ
      metabolites, and fat contained the highest levels of the parent compound. Skin
      contained higher residue levels for all three compounds, compared with muscle
      tissue. MBZ and its hydroxy metabolite were eliminated within 5 days from the
      edible parts (muscle and skin) of the eels, whereas MBZ-NH2 could be detected by
      the 14th day after the end of the treatment period. Consequently, although MBZ
      and MBZ-OH constitute the residues of toxicological concern, MBZ-NH2 should be
      taken as the compound of interest for estimating the withdrawal time for
      consumption of eel treated with MBZ.

PMID- 9172950
TI  - Metabolism of cerivastatin by human liver microsomes in vitro. Characterization
      of primary metabolic pathways and of cytochrome P450 isozymes involved.
AB  - Biotransformation of cerivastatin, a new cholesterol-lowering drug, by human
      liver microsomes was investigated using the 14C-labeled drug. Metabolite profiles
      were established by HPLC and structures of metabolites were elucidated. Two
      metabolic pathways were equally important, demethylation of the benzylic methyl
      other and hydroxylation at one methyl group of the 6-isopropyl substituent. The
      product of combined hydroxylation and demethylation was observed as a minor
      metabolite. During sample preparation the lactone forms of both primary
      metabolites were isolated in small amounts. Detailed structural analysis by NMR
      and LC-ESI-MS showed that hydroxylation occurred with high regio- and
      stereoselectivity. The proposed structures were confirmed by chemical synthesis
      of enantiomerically pure reference compounds. Microsomes from a human
      lymphoblastoid AHH-1 cell line, stably expressing CYP 3A4, catalyzed the
      demethylation reaction. Upon incubation of cerivastatin with human liver
      microsomes in the presence of the specific CYP 3A inhibitor TAO, both
      hydroxylation and demethylation were considerably reduced. This indicates that
      CYP 3A enzymes play a major role in cerivastatin metabolism.

PMID- 9172951
TI  - Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl)-2-ethyl-3
      hydroxypyridin-4-one (CP117) in the rat.
AB  - Metabolism and pharmacokinetics of 1-(2'-trimethylacetoxyethyl]-2-ethyl-3
      hydroxypyridin-4-one (CP117) were studied in the rat. Urinary recovery studies
      were conducted in normal (oral and intravenous) and iron-overloaded rats (500 mg
      Fe/kg body weight; oral only). In normal rats, the majority of the dose recovered
      in the urine was as the hydrophilic metabolite, CP102, accounting for 69.7 +/-
      9.4% (oral) and 80.7 +/- 7.9% (intravenous) of the administered dose. There was,
      however, a dramatic decrease in the amount of CP102 recovered (47.7 +/- 5.9%) (p
      < or = 0.05) in the iron-loaded group of animals. The amount of CP102 glucuronide
      conjugate recovered in the normal and iron-overloaded rats after oral
      administration of CP117 did not differ significantly with values of 6.5 +/- 2.5%
      and 7.1 +/- 2.5%, respectively. There was, however, a significant increase in
      CP102 glucuronide conjugate (13.7 +/- 3.0%) (p < or = 0.05) after intravenous
      administration of CP117. Urinary iron content was determined in the iron
      overloaded and normal (oral) animals. Negligible levels of the CP117 iron complex
      and only 0.6 +/- 0.2% was present as the corresponding CP102 complex in the urine
      of normal animals. Less than 0.1% of the administered dose was recovered as CP117
      iron complex and only 1.3 +/- 0.2% as CP102-iron complex in the iron-overloaded
      animals. Total recovery of the administered dose was significantly different
      between normal (po) and iron-overloaded groups of animals, decreasing from 76.4
      +/- 11.7% to 57.2 +/- 9.6%, respectively (p < or = 0.05). There was no
      significant difference between the two routes of administration in normal
      animals, with total recovery of the administered dose of CP117 being 96.1 +/-
      9.1% by the intravenous route. Intravenous and oral pharmacokinetics of CP117 was
      studied in the rat at a fixed dose of 450 mumol/kg. The AUC of the drug was 43.2
      +/- 9.1 mumol/liter . hr and 4.1 +/- 1.8 mumol/liter.hr via the intravenous and
      oral routes, respectively, thus indicating that the systemic bioavailability of
      the drug is < 10%. Pharmacokinetic parameters of the drug determined by the
      intravenous route indicate that CP117 has a plasma clearance of 10.9 +/- 3.0
      mumol/liter.hr, a mean residence time of 0.14 +/- 0.05 hr, and volume of
      distribution at steady-state of 1.54 +/- 0.52 liters.kg-1. The Cmax and tmax of
      CP117 were 12.1 +/- 2.5 mumol/liter and 7.0 +/- 2.7 min, respectively. The AUC of
      the main metabolite, CP102, decreased from 425.3 +/- 8.5 mumol/liter.hr to 282 +/
      31 mumol/liter.hr via the intravenous and oral routes, which is presumed to
      reflect differences in hepatic extraction and routes of elimination of the drug.
      Parallel absorption studies conducted using the in situ isolated rat gut loop
      model indicate that the majority of the administered dose was absorbed intact as
      the parent drug with mesenteric vein AUC values of 3.1 +/- 1.7 mmol/liter.hr and
      0.3 +/- 0.04 mmol/liter.hr for CP117 and CP102, respectively.

PMID- 9172952
TI  - Biphasic kinetics of quaternary ammonium glucuronide formation from amitriptyline
      and diphenhydramine in human liver microsomes.
AB  - The tricyclic antidepressant amitriptyline and the H1-receptor antagonist
      diphenhydramine are conjugated in human liver microsomes fortified with UDP
      glucuronic acid at their tertiary amino groups with the formation of quaternary
      ammonium glucuronides. The kinetics of the reactions were found to be biphasic
      with apparent KM1 and KM2 values of 1.4 microM and 311 microM for amitriptyline
      and 2.6 microM and 1180 microM for diphenhydramine in four liver samples. Vmax1
      values varied between 2 and 17 pmol-mg protein-1.min-1 for the two substrates and
      Vmax2 values between 80 and 740 pmol-mg protein-1.min-1. A close correlation
      existed between amitriptyline and diphenhydramine glucuronidation rates in
      microsomes from seven livers at concentrations corresponding to 10-40% of KM2. At
      low concentrations, diphenhydramine competitively inhibited the glucuronidation
      of amitriptyline. Vmax/K(M) values of the high-affinity UDP
      glucuronosyltransferase(s) (UGTs) exceed those of the low-affinity enzyme(s)
      severalfold, such that the former should make the major contribution to N
      glucuronidation of the drugs at therapeutic concentrations in vivo.

PMID- 9172953
TI  - Dietary modulation of phase 1 and phase 2 activities with benzo(a)pyrene and
      related compounds in the intestine but not the liver of the channel catfish,
      Ictalurus punctatus.
AB  - These studies demonstrated that intestinal mucosa of the channel catfish
      contained activities comparable with liver for several phase 2 xenobiotic
      metabolizing enzymes, and showed that CYP1A-dependent monooxygenase activities
      were inducible in intestine but not liver by dietary exposure to low
      concentrations of the Ah agonist, beta-naphthoflavone (BNF). The diets
      administered were laboratory-prepared, semisynthetic pellets of known
      composition, commercial chow, or chow supplemented with BNF at 10 or 100 mg
      BNF/kg chow. Very low intestinal benzo(a)pyrene hydroxylase [aryl hydrocarbon
      hydroxylase (AHH)] and ethoxyresorufin O-deethylase (EROD) activities were found
      in catfish fed the semisynthetic diet. Intestinal EROD and AHH activities were
      elevated by the commercial chow diet and further induced by supplementation with
      10, but not 100, mg BNF/kg diet. In vitro studies showed that catfish EROD and
      AHH activities were sensitive to inhibition by BNF, with mean IC50 values of
      0.078 and 2.2 microM, respectively. Thus, residues of BNF retained in intestinal
      mucosa may have masked monooxygenase induction in catfish fed the 100 mg BNF/kg
      diet. Microsomal UDP-glucuronosyltransferase and cytosolic PAPS-sulfotransferase
      activities with 3-hydroxybenzo(a)pyrene as substrate were largely unaffected by
      the diets studied, and intestinal activities were similar to hepatic activities.
      Glutathione S-transferase activity was slightly induced in intestinal, but not
      hepatic cytosol of catfish treated with BNF at the 10 mg/kg diet level relative
      to chow controls. Epoxide hydrolase activity with styrene oxide as substrate was
      not affected by diet in intestinal microsomes.

PMID- 9172954
TI  - Disposition of L-738,167, a potent and long-acting fibrinogen receptor
      antagonist, in dogs. Dose-dependent pharmacokinetics.
AB  - L-738,167 is a potent and long-acting fibrinogen receptor antagonist and may be
      useful for treatment of chronic thrombotic occlusive disorders. The purposes of
      this study were to characterize the metabolism and disposition of L-738,167, and
      to investigate factors affecting its pharmacokinetic behaviors in dogs, one of
      the animal models used in pharmacological and toxicological studies. In vitro and
      in vivo experiments indicated that L-738,167 was not metabolized to any
      appreciable extent in dogs. Biliary excretion was found to be the major route
      (approximately 75%) of drug elimination. Following 1 and 3 micrograms/kg iv
      doses, blood pharmacokinetics of L-738,167 were linear. Total blood clearance
      (CLB) was much lower than hepatic blood flow, and the apparent volume of
      distribution at steady-state (Vdss,B) was comparable with blood volume. Blood
      pharmacokinetics in the dose range of 3-250 micrograms/kg were dose-dependent;
      both CLB and Vdss,B for L-738,167 increased markedly with increasing doses.
      However, the terminal half-life (t1/2) was dose-independent, with a mean value of
      approximately 4 days. L-738,167 was found to bind negligibly to dog plasma
      proteins. Determinations of whole blood (WB), platelet-rich plasma, and platelet
      poor plasma concentrations after several intravenous doses of [3H]L-738,167
      revealed significant concentration-dependent binding of the compound to
      platelets. Kinetic analysis of the platelet binding indicated that L-738,167 was
      bound to dog platelets with high affinity (apparent Kd approximately 1 nM
      platelet-poor plasma concentration) and relatively low capacity (approximately 70
      nM WB concentration). Findings are consistent with the binding kinetics of L
      738,167 to glycoprotein IIb/IIIa (GP IIb/IIIa) receptor, supporting that GP
      IIb/IIIa was the primary binding component on the platelets. It was concluded
      that the dose-dependent pharmacokinetics of L-738,167 were the consequence of the
      concentration-dependent drug-platelet binding. Due to this extensive platelet
      binding, L-738,167, when given in therapeutic doses or lower, resided primarily
      in the vascular compartment-the site of pharmacological action. At doses
      exceeding the receptor binding capacity, the excess amount or the unbound drug
      was eliminated rapidly. In all cases, the equally long t1/2 of L-738,167 was also
      a consequence of the high-affinity binding to platelets, in good agreement with
      its prolonged pharmacodynamic profile.

PMID- 9172955
TI  - Pharmacokinetics and metabolism of selected prodrugs of PMEA in rats.
AB  - The oral bioavailability of PMEA [9-[2-(phosphonomethoxy)ethyl]adenine; adefovir)
      has been determined in rats from three bisester prodrugs of PMEA: bis
      (pivaloyloxymethyl) PMEA (bis-POM PMEA), bis-(phenyl) PMEA, and bis-(o
      ethoxyphenyl) PMEA. The prodrugs were each administered to 9 male rats as
      solutions in PEG 400 at a dose of 10 mg-equivalent of PMEA per kg. Plasma samples
      were obtained over the course of 12 hr and concentrations of PMEA were determined
      by fluorescence derivatization and analysis by HPLC. Concentrations of PMEA
      observed in plasma following oral administration of PMEA prodrugs were compared
      with levels observed for intravenous PMEA. The observed oral bioavailabilities of
      PMEA from bis-POM PMEA, bis-(phenyl) PMEA, and bis-(o-ethoxyphenyl) PMEA were
      38.2%, 2.46%, and 40.1%, respectively. PMEA was the only metabolite formed after
      oral administration of bis-POM PMEA. Three metabolites were detected after oral
      administration of either bis-(phenyl) PMEA or bis-(o-ethoxyphenyl) PMEA to rats:
      PMEA, the corresponding monoester, and 2-adenylacetic acid. The major metabolite
      of bis-(phenyl) PMEA was 2-adenylacetic acid following oral administration. 2
      Adenylacetic acid appears to have been formed from the intact prodrugs by a P450
      mediated oxidation of the ethyl side chain.

PMID- 9172956
TI  - Human colorectal carcinoma cells in vitro as a means to assess the metabolism of
      analogs of mycophenolic acid.
AB  - Cultures of the human colorectal carcinoma line, HT29, were used to assess the
      susceptibility to glucuronidation of the cytostatic, immunosuppressive drug
      mycophenolic acid (MPA) and 19 of its analogs. Removal of the metabolically
      vulnerable 7-hydroxyl group or its replacement by a fluorine atom, amino group,
      or nitrile group resulted in compounds that were completely resistant to
      metabolism, but that had substantially lower antiproliferative potency against
      the EMT6 carcinoma line that is unable to glucuronidate MPA. In compounds
      retaining the 7-hydroxy function replacement of the lactone moiety of the
      phthalane ring of MPA by either a cyclopentanone or a 6-membered lactam afforded
      some protection against metabolism, but also partially or completely suppressed
      antiproliferative activity. Some lipophilic substituents at position 2 of the
      hexenoic side chain in analogs with the 7-hydroxy function resulted in increased
      metabolism, whereas several substituents with increased steric bulk in this
      position (including benzyl, p-hydroxyphenyl, trifluoroacetamidophenyl,S-methyl,
      and methoxymethyl) markedly inhibited metabolism. The last three of these
      derivatives also maintained or exceeded the antiproliferative potency of MPA. We
      suggest that cultures of human colorectal carcinoma cells lines may provide a
      rapid and convenient means of assessing the susceptibility of novel synthetic
      compounds to both phase I and phase II metabolic conversions.

PMID- 9172958
TI  - Pharmacokinetics of SNX-111, a selective N-type calcium channel blocker, in rats
      and cynomolgus monkeys.
AB  - SNX-111, a selective N-type voltage-sensitive calcium channel blocker, is in
      clinical trials for the treatment of ischemia-induced brain injury and chronic
      pain. Pharmacokinetic studies were conducted in rats and cynomologus monkeys to
      determine the disposition of this compound when it is administered for 24 hr by
      continuous, constant-rate intravenous infusion. Venous blood samples for
      determination of SNX-111 plasma levels were collected at regular intervals
      immediately before, during, and after dosing. Plasma concentrations of SNX-111
      equivalents were measured by radioimmunoassay. Pharmacokinetic parameters were
      derived from plasma SNX-111 concentration-time data using a two-compartment
      pharmacokinetic model. Results showed close correspondences between
      pharmacokinetic parameters determined for both species. There were no consistent
      gender- or dose-related differences in calculated kinetic parameters. In all
      cases, apparent steady-state plasma SNX-111 concentrations were achieved within 2
      4 hr of initiating SNX-111 infusion. Steady-state volume of distribution values
      were approximately 40% of body weight, indicating extravascular dissemination of
      SNX-111 to both extracellular and intracellular fluids. Elimination curves
      contained two exponential components. The fast component (rat t1/2, alpha = 0.375
      hr; monkey t1/2, alpha = 0.730 hr) accounted for approximately 97% of the unit
      impulse disposition function. The apparent terminal half-life ranged from 4.61 hr
      (rat) to 6.48 hr (monkey). Current findings constitute the first description of
      the pharmacokinetics of a member of the omega-conopeptide family of neuronal
      calcium channel blockers.

PMID- 9172957
TI  - Absorption, disposition kinetics, and metabolic pathways of cyclohexene oxide in
      the male Fischer 344 rat and female B6C3F1 mouse.
AB  - Cyclohexene oxide (CHO) is a monomer intermediate used in the synthesis of
      pesticides, pharmaceuticals, and perfumes. Although CHO has a variety of
      industrial uses where direct human exposure is possible, very little is known
      about its fate in the body. Therefore, the objectives of this study were to
      determine the absorption, distribution, metabolism, and excretion of cyclohexene
      oxide after oral, intravenous, and dermal exposure in male Fischer 344 rats and
      female B6C3F, mice. After intravenous administration of [14C]CHO (50 mg/kg), CHO
      was rapidly distributed, metabolized, and excreted into the urine. Plasma
      concentrations of CHO rapidly declined and were below the limit of detection
      within 60 min. Average (+/- SD) values for terminal disposition half-life,
      apparent volume of distribution at steady-state, and systemic body clearance
      were: 19.3 +/- 1.6 min; 0.44 +/- 0.08 liter/kg; and 31.3 +/- 0.5 ml/kg * min,
      respectively. After oral administration of [14C]CHO (10 and 100 mg/kg), it was
      found that 14C-equivalents were rapidly excreted in the urine of both species. At
      48 hr, the majority of the dose (73-93%) was recovered in urine, whereas fecal
      elimination accounted for only 2-5% of the dose. At no time after oral
      administration was parent CHO detected in the blood. However, its primary
      metabolite cyclohexane-1,2-diol was present for different lengths of time
      depending on the dose. Four metabolites were detected and identified in mouse
      urine by MS: cyclohexane-1,2-diol; cyclohexane-1,2-diol-O-glucuronide; N-acetyl-S
      (2-hydroxycyclohexyl)-L-cysteine; and cyclohexane-1,2-diol-O-sulfate. The sulfate
      conjugate was not present in rat urine. Topical application of [14C]CHO (60
      mg/kg) provided poor absorption in both species. The majority of 14C-equivalents
      applied dermally were recovered from the charcoal skin trap (approximately 90% of
      the dose). Only 4% of the dose was absorbed, and the major route of elimination
      was via the urine. To evaluate the toxicity of CHO, animals were given daily
      doses of CHO orally and topically for 28 days. No statistically significant
      changes in final body weights or relative organ weights were noted in rats or
      mice treated orally with CHO up to 100 mg/kg or up to 60 mg/kg when given
      topically. Very few lesions were found at necropsy, and none were considered
      compound related. In conclusion, regardless of route, CHO is rapidly eliminated
      and excreted into the urine. Furthermore, after either oral or dermal
      administration, it is unlikely that CHO reaches the systemic circulation intact
      due to its rapid metabolism, and is therefore unable to cause toxicity in the
      whole animal under the test conditions used in this study.

PMID- 9172959
TI  - Mechanism-based inactivation of mouse hepatic cytochrome P4502B enzymes by amine
      metabolites of musk xylene.
AB  - Musk xylene (2,4,6-trinitro-1-t-butylxylene; MX) is a synthetic nitromusk perfume
      ingredient that induces and inhibits mouse cytochrome P4502B (CYP2B) enzymes in
      vivo. The purpose of the present work was to determine whether amine metabolites
      of MX contributed to the enzyme inhibition and, if so, to define the nature and
      kinetics of this inhibition. When dosed orally to phenobarbital (PB)-treated
      mice, MX (200 mg/kg) inhibited > 90% of the PB-induced O-dealkylation of 7
      pentoxyresorufin (PROD), and [14C]MX equivalents bound covalently to microsomal
      proteins. However, when this experiment was repeated in mice pretreated with
      antibiotics to eliminate the gastrointestinal flora, no decrease in PB-induced
      PROD activity and no covalent binding to microsomal proteins were observed. Thus,
      the ability of antibiotic treatment to eliminate the enzyme inhibition and
      covalent binding implicated amine metabolites of MX formed by nitroreduction in
      anaerobic intestinal flora as obligatory for these effects. Two monoamine
      metabolites of MX were synthesized to study enzyme inhibition directly. These
      metabolites were 2-amino-4,6-dinitro-1-t-butyl-xylene and 4-amino-2,6-dinitro-1-t
      butylxylene, referred to as o-NH2-MX and p-NH2-MX, respectively, reflecting the
      position of the amine substitution relative to the t-butyl function. In the in
      vitro studies with PB-induced mouse liver microsomes, both amines inhibited PROD
      activity when preincubated in the absence of NADPH. However, only p-NH2-MX caused
      a time- and NADPH-dependent loss of PROD activity, and the inactivation rate was
      a pseudo-first-order process that displayed saturation kinetics. These results
      indicate that p-NH2-MX is a mechanism-based inactivator of mouse CYP2B enzymes.
      From kinetic analyses, the Ki was calculated to be 10.5 microM and the Kinact was
      1.2 min-1. As final confirmation of the inhibitory effects of p-NH2-MX on mouse
      CYP2B enzymes, the amine (0.67 mmol/kg) was dosed orally to PB-induced mice. At 2
      hr after dosing, p-NH2-MX inhibited essentially all of the PB-induced PROD
      activity, whereas an equimolar dosage of parent MX had no effect at this early
      time. Thus, although MX is an inducer of mouse CYP2B enzymes, an amine metabolite
      of MX is a mechanism-based inactivator of mouse CYP2B10. Furthermore, it is
      likely that the amine is responsible for the lack of functional CYP2B enzyme
      activity associated with induction of this enzyme by MX.

PMID- 9172960
TI  - Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human
      liver microsomes.
AB  - The specificities of orphenadrine and methimazole on eight human liver P450
      enzyme activities were evaluated by studying the extent of inhibition at
      different concentrations in two protocols: competitive inhibition and
      preincubation. In the competitive inhibition protocol, orphenadrine decreased
      CYP2B6 marker activity up to 45-57% in human liver microsomes and up to 80-97% in
      cell microsomes containing cDNA-expressed CYP2B6. Orphenadrine strongly decreased
      CYP2D6 marker activity by 80-90%. Orphenadrine also partially decreased the
      CYP1A2, CYP2A6, CYP3A4, and CYP2C19 marker activities. In the preincubation
      protocol, orphenadrine decreased the CYP2B6 activity in cDNA-expressed cell
      microsomes to completion. In human liver microsomes, orphenadrine strongly
      decreased the marker activities of CYP2B6, CYP2D6, as well as CYP2C9; and
      partially decreased the marker activities of CYP1A2, CYP2A6, CYP3A4, and CYP2C19.
      In the competitive inhibition protocol, methimazole had no effect on the marker
      activities of CYP2E1 and CYP2A6; slightly decreased CYP2D6 marker activity;
      partially decreased the marker activities of CYP2C19, CYP2C9, and CYP2B6; and
      dramatically decreased CYP3A4 marker activity. Methimazole decreased CYP1A2
      marker activity at lower concentrations, but not at the highest concentration
      studied (1 mM). In the preincubation protocol, methimazole was shown to be a
      potent and nonspecific inhibitor of all the enzyme activities. Marker activities
      of CYP2C9, CYP2C19, and CYP3A4 were completely inhibited at relatively low
      concentrations. This study indicates orphenadrine cannot be used as a selective
      inhibitor of CYP2B6 in human liver microsomes and that methimazole is not a
      selective inhibitor of the flavin-containing monooxygenase in human liver
      microsomes.

PMID- 9172961
TI  - [Psychometric properties of PANSS (Positive and Negative Syndrome Scale) in the
      French version in a sample of schizophrenic patients].
AB  - Our study focuses on psychometrics properties of the french version of the
      Positive and Negative Syndrom Scale (PANSS). 85 schizophrenic subjects, in
      accordance with DSM III-R criteria were included in this study. Our results allow
      us to discuss the construct validity and the reliability of this scale. The
      traditional 3 dimensions of the PANSS (positive, negative and general
      psychopathology) are discuss. We show that expect positive scale and general
      psychopathology scale average several symptomatic dimensions. We propose a 5
      dimensions solution (negative, hostility, positive, disorganization, anxiety),
      which represent 54% of the total inertie. The internal consistency of this
      solution is presented.

PMID- 9172963
TI  - [Statistical results: which method of presentation to chose?].
AB  - Hypothesis testing and significance is currently the most widely used method in
      the medical literature to report statistical results. However, this method has
      several limitations. The main one is linked to the risk of misinterpretation of
      the p value. The arbitrariness of the 5 percent value used to determine whether a
      result is or not statistically significant is not always kept in mind, and the
      concept of statistical significance might therefore be confused with that of
      clinical or biological relevance. The misinterpretation pitfalls are mostly
      linked to the fact that the p value does not give precise indications on the
      strength of the association and its direction, or on the variability in the
      sample. Therefore, some experts claim that hypothesis testing and significance
      should be avoided in reporting statistical results, and that the method based
      upon estimation and confidence interval should be more widely used. By this
      latter method, it is possible to know the direction of the association and the
      effect size (i.e. the strength of the association). The precision of the
      estimation, i.e. the variability of the estimation in the sample, can be assessed
      by the width of the confidence interval: the narrower the confidence interval,
      the more precise the estimation. Therefore, the clinical relevance of the
      findings is easier to infere from such results than from those only reporting p
      values. However, the estimation and confidence interval method is not without its
      own limitations. This method is difficult to apply to non-parametric tests, and
      for some results, such as the comparison of mortality ratios, the p value is
      highly informative. On the other hand, the misinterpretation risk is not totally
      ruled out when estimation and confidence interval method is used. In the
      situations where both methods can be employed, there is not yet in the scientific
      community a definite consensus on which method is the best one to report
      statistical results, hence some experts suggest that both methods can be
      presented simultaneously, especially for clinical and epidemiological studies.

PMID- 9172962
TI  - [A four-dimensional model of chronic schizophrenia based on the factorial
      structure of the Positive and Negative Syndrome Scale (PANSS). A study of a group
      of 153 chronic schizophrenic patients and comparison with the factorial structure
      of the BPRS].
AB  - The aim of the study is to explore the latent dimensions in chronic schizophrenia
      using factorial analysis methods. 153 subjects (89 males, 64 females) with a mean
      age of 38.83 years (sd = 10.15) meet the RDC criteria for chronic schizophrenia
      and were included in the study. They were 127 inpatients and 26 outpatients and
      the mean duration of the illness since the first psychotic episode was 14.69
      years (sd = 9.64). The majority of the schizophrenics received antipsychotic
      treatment with a mean dose (in chlorpromazine-equivalent) of 401.86 mg (sd =
      368.13). The schizophrenics were rated using the French versions of the Positive
      and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale
      (BPRS). Two successive principal components analyses (PCA) were carried out on
      the correlation matrix of the 30 PANSS and 18 BPRS items. The numbers of factors
      were limited using several guidelines : eigenvalues higher than 1, screen test
      and the parallel analysis of Horn. Then an orthogonal equamax rotation was made
      and the saturation value was chosen using and ad-hoc paradigm. The results have
      shown a four-factors solution for the PANSS with the following factors :
      negative, positive-hostility, disorganization-impulsivity, depressive-anxious.
      The composition of the four preceding factors was respectively : negative [N1,
      N2, N3, N4, N6, N7, G7, P4 (-)]; positive-hostility (P1, P2, P3, P5, P6, P7, G8,
      G9, G12, G15, G16); disorganization-impulsivity (G5, G10, G11, G13, G14, N5);
      depressive-anxious (G1, G2, G3, G4, G6). The ACP of the BPRS have shown a three
      factors solution (positive-disorganization, negative, depressive-anxious). The
      factorial structure of the PANSS was discussed with the different studies. Our
      results confirm the division of the productive symptomatology into two
      components, delusions-hallucinations and cognitive (disorganization). Moreover
      depressive and negative symptomatology constitute two separate dimensions.
      Contrary to the others studies we did not find an excited component, the
      corresponding items were found in the positive and disorganization factors. The
      inclusion of solely chronic schizophrenics could explain the lack of the excited
      component. Our data in chronic schizophrenia allow us to propose a four
      dimensional model explaining the symptomatology of this disease.

PMID- 9172964
TI  - [Dynamic DNA mutations, anticipation and schizophrenia].
AB  - Recently, a new form of human mutation-expansion of trinucleotide repeats-has
      been found to cause fragile X syndrome, Huntington's disease and other
      neurodegenerative diseases. These diseases are characterized by unusual patterns
      of inheritance, in particular, genetic anticipation in which the severity of the
      disorder increases and the age at onset decreases in successive generations of a
      pedigree. This phenomenon, formerly ascribed to observation biases, correlates
      with the expansion of trinucleotide repeat sequences. Two recent studies indicate
      that anticipation is present in familial schizophrenia. These findings support
      both an active search for unstable trinucleotide repeat sequences in
      schizophrenia and reconsideration of the genetic models used in this disorder.

PMID- 9172965
TI  - [Natural history of infantile autism (nosography)].
AB  - Natural history of infantile autism goes from its first description to current
      classifications. Most authors agree upon the perfect character of Kanner's
      description in 1943. But its situation in the nosography has much developed. The
      parution of 4th edition of Diagnostic and Statistical Manual of mental disorders
      (DSM IV) bring us to analyse this evolution and the place of autistic disorders
      in the pervasive developmental disorders, with this of associated pathologies.
      The comparison of current classifications (DSM IV, ICD 10, CFTMEA) allows us to
      do correspondence between each diagnostic category in psychosis or developmental
      disorders of these classifications. It exists a real concordance between DSM IV
      and ICD 10. The french classification of child and adolescent mental disorders
      (CFTMEA) proposes original categories.

PMID- 9172966
TI  - [Frontal lobe cognition disorders in 42 schizophrenic patients compared with 19
      normal probands].
AB  - In schizophrenia, the hypothesis of frontal dysfunctions is sustained by various
      clinical, neuroradiological and neuropsychological observations. We have studied
      the degree of frontal cognitive impairment in 42 schizophrenic patients according
      to the DSM IV as compared to 19 normal subjects. Furthermore, the performances of
      the different tests were connected with the age, the duration of the disease, the
      severity of the illness (measured by the PANSS scale) and the incidence of the
      treatments. The neuropsychological tests used in this study were the D48, the
      Wisconsin card sorting test, the Stroop color and word test, the word fluency and
      a target detection test. The results obtained from this study agree with the
      occurrence of frontal cognitive impairments in schizophrenia. Such impairments
      are increased with the age and the duration of the disease.

PMID- 9172967
TI  - [Memory complaints and anxiety. Apropos of 40 patients attending a specialized
      memory consultation].
AB  - This study reports results of the specialized memory consultation based on 2
      successive examinations, one by a neurologist, the other by a psychologist, of 40
      anxious subjects with or without social phobias. Traumatic events were frequent
      and we observed Alzheimer's disease in the family of 41.9% of subjects. Anxious
      subjects obtained a high score in Mac Nair questionnaire [44.05 (16,49)]. Their
      principal complaints were attentional difficulties. They obtained normal but low
      performances for free recall of 10 pictures, logical memory (QM), and inverse
      span. Mac Nair score was only correlated with logical memory score. Standardized
      psychometric evaluation showed short-term memory difficulties. Attention seems to
      be unstable and anxious individuals have relatively limited attentional
      resources. They are preoccupied by their anxiety and thus have less ability to
      focus on tasks.

PMID- 9172969
TI  - [Value of tianeptine in treating major recurrent unipolar depression. Study
      versus placebo for 16 1/2 months of treatment].
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of tianeptine vs
      placebo in the long-term treatment of unipolar major recurrent depression.
      METHOD: 286 patients who met DSM-III-R criteria for major depression with a
      Hamilton Depression Rating Scale (HDRS-21 items) score > or = 17, and with a
      history of at least one previous episode within the last 5 years, were treated in
      an open trial with tianeptine for 6 weeks. 185 patients who responded to
      treatment at day 42 (intent-to-treat) were randomly assigned to tianeptine 37.5
      mg/day (n = 111), or placebo (n = 74). Among these patients 173 were strict
      responders to tianeptine (per-protocol-population), as defined in the present
      study by a 50% reduction in the HDRS score, a global score lower than 15 and
      confirmation by clinical evaluation. Both groups were comparable except for the
      severity of the depressive episode (significantly more severe in the tianeptine
      group (33%) than in the placebo group (18%)) (p = 0.018). Relapses and
      recurrences were defined by a HDRS score > or = 15, and/or a CGI score > or = 4,
      the recurrences being confirmed by the clinician. Patients were subsequently
      evaluated at day 63, and the 3rd, 6th, 9th, 12th, 15th and 18th month. RESULTS:
      Special attention was given to the number of relapses and recurrences, and to the
      delay of onset (Kaplan Meier Method). Between day 42 and 18th month (intent-to
      treat group), the rate of relapses and recurrences was significantly higher in
      the placebo group (36%), than in the tianeptine group (16%) (p = 0.002). Long
      term comparison of the rate of patients without recurrence or relapse, also
      showed a significant difference in favour of tianeptine (p < 0.001). The
      difference between teh 2 groups increased within time. Secondary analysis of
      relapses and recurrence in the intent-to-treat group showed a significantly
      higher rate of relapses for the placebo group (p = 0.002); the rate of patients
      without recurrences in the long term appeared to be at the limit in the intent-to
      treat group (p = 0.067) but significant in the per-protocol-group, in favour of
      tianeptine (p = 0.36). Furthermore, no difference was observed between the 2
      groups, in terms of tolerance. Secondary effects attributed to treatment by
      investigators were rare and benign in each group. CONCLUSIONS: These data support
      the use of tianeptine in the long term treatment of unipolar major recurrent
      depression. Relapses and recurrences were 2 to 3 times less frequent with
      tianeptine as compared to placebo. Furthermore, prolonged treatment with
      tianeptine appeared to be very well tolerated.

PMID- 9172968
TI  - [Maprotiline versus fluvoxamine: comparison of their effects on the hypothalamo
      hypophyseal-thyroid axis].
AB  - The TRH test has been used in psychiatry these last 20 years. One of the most
      promising results is that concerning the possibility to use it to identify the
      best moment to stop a treatment after clinical recovery of the depressive
      episode. For that it is necessary to demonstrate an absence of intrinsic action
      of antidepressants on the HPT axis physiology. This overt, randomized study has
      compared the actions on T3, T4, basal TSH and its response to the TRH test after
      75 mg/day of maprotiline and 100 mg/day of fluvoxamine, both administrated in
      depressed patients during 28 days. Forty patients (20 men and 20 women) were
      studied, 20 patients per treatment. The inclusion criteria were those of DSM III
      R for major depression and dysthymia as well a minimum score of 25 at MADRS
      scale. Blood samples for T3, T4 and basal TSH dosages were made before TRH
      intranasal administration (2 mg) at days 1 and 28 of the treatment. We haven't
      observed any difference before treatment between the 2 groups for clinical and
      biological studied parameters. After treatment both antidepressants produced
      equivalent improvement of depression evaluated by MADRS (fluvoxamine:dMADRS =
      16.95 +/- 7.11; maprotiline: dMADRS = 17.10 +/- 6.84. t = 0.07, NS). T3 and T4
      variations between the beginning and the end of the study weren't also
      significantly different between the 2 groups. Basal TSH was increased in the
      maprotiline group but decreased in the fluvoxamine group resulting in a
      significant difference (fluvoxamine: dTSH = 0.31 +/- 0.76 mUI/l. Maprotiline :
      dTSH = -0.23 +/- 0.66 mUI/l. t = 2.40, p < 0.02). The TSH response to TRH was
      decreased in the fluvoxamine group (ddTSH = 0.24 +/- 6.65 mUI/l. dAUC = 103.98 +/
      596.84 mUI/l) while it was increased in the maprotiline group (ddTSH = -3.59 +/-
      5.88 mUI/l. dAUC = -355.80 +/- 505.67 mUI.min/l). The difference between the 2
      treatments was not significant when evaluated by ddTSH (t = 1.53, NS) but it
      became significant if evaluated by dAUC (t = 2.63, p < 0.01). As we could
      demonstrate an absence of influence of the clinical evolution between both groups
      in the hormonal variations observed, we concluded to a intrinsic difference
      action on HPT axis between fluvoxamine and maprotiline. This difference could be
      linked to the different aminergic action of these 2 antidepressants.

PMID- 9172970
TI  - [Controlled study of outcome after 6 months to early intervention of bus driver
      victims of aggression].
AB  - The aftermath of psychological trauma, long since studied in the context of war
      ("soldier's heart", "shell shock", etc.) can also occur as a result of trauma in
      civilian life. Bus drivers in large urban area are frequently aggressed. Over a
      period of 5 months, bus drivers who had been aggressed, employees of the largest
      French urban transport company (RATP), participated in a study designed to
      evaluate the effects of cognitive behavior treatment provided shortly after such
      aggression. A total of 132 bus drivers were included in the study divided into 2
      randomized groups: a control group (67 subjects) received the usual medical
      social care offered by the company, and a treatment group (65 subjects) who, in
      addition, benefited from 1 to 6 sessions of cognitive behavior intervention,
      including:evocation of the aggression, relaxation, role plays, cognitive
      restructuring. Subjects were evaluated by self-questionnaires a few days post
      aggression and re-evaluated 6 months later. At follow-up, results showed a
      statistically significant decrease in anxiety levels (measured by the HAD scale)
      and intrusion of the traumatic memory (as evaluated by the Horowitz scale) in the
      treatment group. Hence, early and structured intervention appears to lessen the
      impact of the traumatic event on bus drivers attacked at work.

PMID- 9172971
TI  - [Creutzfeldt-Jakob disease and psychiatry. Apropos of a case].
AB  - Creutzfeldt-Jakob disease is relatively poorly documented in psychiatry. An
      observation will be presented concerning a 69 years old patient admitted for
      conduct disorder and prosecution delirium. In fact, the symptomatology associated
      dementia, transient confusion, parkinsonism, ataxia and abnormal movements. In
      the checkup the electroencephalogram gave us an important orientation for
      diagnosis. After a thoracic trauma the patient was admitted in an intensive care
      unit with a positive pressure ventilation. His general condition worsened until
      he died. Brain histic exploration and PRP gene analysis confirmed the diagnosis.
      Even if there is no efficient treatment, such a diagnosis has to be done in order
      to take prophylactic measures and conduct epidemiological surveys.

PMID- 9172972
TI  - [Need for recognizing bipolar disorders in all its forms].

PMID- 9172973
TI  - [Emil Kraepelin and bipolar disorder: invention or over-extension?].
AB  - From 1899 to 1913, Emil Kraepelin (1856-1926) creates and elaborates the
      nosographical group of the "manic-depressive insanity". In the 50-60s, Leonhard
      splits off this homogeneous group and describes unipolar psychosis, bipolar
      psychosis and cycloid psychosis (anxiety-elation psychosis, motility psychosis
      and confusion psychosis). Recent nosographical orientations seem to announce a
      come-back to Kraepelin's conception of "mood disorders". This paper presents the
      essential of Kraepelin's "manic-depressive insanity" theory-temperamental basis,
      integration of mixed states, epidemiological datas- and highlights its
      dialectical relations with today's theory of bipolarity.

PMID- 9172974
TI  - [Disposition toward mood genes].
AB  - Genetic factors together with psychological heredity have been involved in the
      genesis of mood disorders for a long time. Beside chromosomes X and 11, many
      other tracks exist. Results are heterogeneous and likely because of clinical,
      etiopathogenic and genetic heterogeneity of these diseases. Studies multiplicity
      strengthen the determinism complexity of the mood disorders. Since positive
      results published remain poorly replicated they receive from readers a reception
      as variable as the mood changes of the illnesses they concern. However, these
      studies lead to a better definition of their limits. Either clinical, biological
      or genetic, these limits would be on the decline and human genetic applied to
      psychiatry might improve etiopathogenic and therapeutic knowledges of mood
      disorders.

PMID- 9172975
TI  - [Psychological factors and life change events in bipolar patients].
AB  - This article purpose is to discuss the major hypotheses concerning the
      relationship of personality to bipolar disorders. The data are reported and
      commented. Life events are introduced to confirm the influence of psychological
      factors in the course of these disorders, supposed to be endogenous. The status
      of bipolar disorder is discussed. The unitary model of major affective disorders
      could allow to answer the questions raised by the data.

PMID- 9172976
TI  - [Tools for clinical evaluation of affective temperaments].
AB  - The authors argue from an "adult" perspective, that clinically ascertained
      affective dysregulations are prevalent in the prebipolar history. This hypothesis
      is based: 1) on early age of onset; 2) gender ratio; 3) high propensity to mood
      switching under antidepressant treatment; 4) high rate of recurrence; 5) family
      affective loading and; 6) the frequent superposition of major episodes on
      affective temperamental dysregulation (prominence of mood lability and explosive
      anger: indicators of mixed states). The authors submit that affective
      temperaments (cyclothymic, hyperthymic and dysthymic) represent putative
      developmental pathways to bipolarity. A french version of the semi-structured
      interview and self-assessment of affective temperaments had been constructed by
      the authors. The french version of these psychometric tools is presented in this
      chapter. The authors hoped that current knowledge and new research in the domain
      of affective temperaments will encourage clinicians to further understanding the
      manic-depressive illness and to make early detection of different clinical
      expressions of bipolarity. More clinical sophistication is needed to go beyond
      the classical "diagnostic" instruments and artificial classifications (as in DSM
      IV) and to delineate the psycho-biological pathways to bipolarity.

PMID- 9172977
TI  - [Suicidal risk in bipolar disorders].
AB  - Mortality and morbidity are greatly increased in patients with mood disorders,
      due to suicide, cardiovascular and other diseases. Recent data for bipolar
      disorders have been released: the suicidal risk is very high in these patients,
      whereas a long term treatment with lithium brings down morbidity to the rate of
      general population. There are no data for other mood stabilizers on this subject.
      Further studies are needed in order to confirm that long term prophylaxy with new
      compounds (valpromide, carbamazepine, etc.) is also efficacious, concerning this
      aspect, especially in bipolar II, mixed states and dysphoric mania. There is a
      dearth of research in the field of the "bipolar spectrum" (soft bipolar
      pathology).

PMID- 9172978
TI  - [Role of associations in bipolar patients].
AB  - Providing information to the patients and their families represents one of
      today's new conditions in the management of the depressed. It will help their
      adaptation to the illness and its effects. It will maintain a good therapeutic
      alliance among patients and practitioners, and will enhance their treatment
      adherence thus improving their quality of life. Several aspects are essential in
      the transmission of this information: it must be available to every patient,
      easily accessible, concise, repeated and revised as necessary, discouraging self
      diagnosis and self-prescription. This education must be given personally by the
      physicians and the pharmacists. Depressed patients may also have an access to
      complementary sources: books, magazines and more rarely scientific journals.
      Patients' associations provide another potential source of information, offering
      a comprehensive approach to the patient and the illness. France-Dexpression is a
      depressive and manic-depressive patients association. Its goals are to provide
      information and support to the patients and their families, promoting a better
      understanding and recognition of depressive and manic-depressive illness.

PMID- 9172979
TI  - [Economic impact of bipolar mood disorders].
AB  - The implementation of spending control policies to combat rising healthcare costs
      and public health department deficits in the industrialised countries poses the
      problem of how to maintain high standards of treatment and ensure quality of life
      for patients. Only a proper medico-economic evaluation of the various therapeutic
      strategies available will allow the two sides of this equation to be reconciled;
      one wonders in fact whether these two sides are indeed contradictory. This is
      particularly true as regards the treatment of mental illnesses. Because of their
      chronic status, together with inherent problems of diagnosis and management,
      bipolar disorders appear at first sight to present a marked impact in economic
      terms, and are thus highly problematic for health authorities. Budgetary control
      is far more complex than simple management of scarce resources, since the least
      expensive therapies are not necessarily the most cost-effective. Nevertheless,
      data allowing accurate assessment of the costs related to these disorders are
      rare or non-existent. Furthermore, the impact of a given treatment for bipolar
      disorders on the quality of life of the patient may have a direct economic
      bearing if one takes account of additional drug consumption and further social
      deficit resulting from unsuccessful therapy, as well as of social and family
      problems related to this type of disorder.

PMID- 9172980
TI  - [Epidemiology of bipolar disorders. Current studies].
AB  - The prevalence of bipolar disorder over a lifetime, which is similar to that for
      one year since this is a chronic disease, is around 1% of the general population.
      Estimates of incidence vary (0.3 to 3 cases per 10000). This general morbidity
      corresponds quite closely to that found in institutions, since patients
      presenting with bipolar disorders are not necessarily in care. Bipolar disorder
      affects men and women in equal proportions, and independently of ethnic and
      cultural background or of socio-economic status. It is nevertheless more
      prevalent in urban than in rural areas, and is more common in subjects who are
      divorced, separated or have never married than in married subjects who have never
      divorced. It mainly affects younger subjects, with the mean age of onset being
      about 20 years. Furthermore, it appears to be more common in subjects born since
      1930-1940. Finally, it is often associated with other mental disorders,
      particularly alcoholism and drug dependence.

PMID- 9172981
TI  - Selections from current literature: mild hypertension.

PMID- 9172982
TI  - [The successful path of the Gaceta Medica de Mexico].

PMID- 9172983
TI  - [The role of the Academia Nacional de Medicina in the field of continuing medical
      education].

PMID- 9172984
TI  - [Trends in medical education].
AB  - Trends in medical education include those occurring in medical practice, related
      with its contents, and in the educational sciences, related with methods and
      technics that could be employed. Trends in medical practice are related to
      epidemiologic, demographic and economic transitions, with the overwhelming
      influence of medical technology, specially molecular biology, the increasing
      social regulation, evidence based medicine and transdisciplinary contributions.
      In the field of pedagogy, trends include the acceptance of the strategic value of
      medical education, the importance of quality-and not only of covering, the
      attention to educational necessities, the recognition of the adulthood of most of
      the learners, the importance of its individual differences and the application of
      new educational technics.

PMID- 9172985
TI  - [The efficacy of sleep hygiene measures in the treatment of insomnia].
AB  - In order to compare the efficacy of sleep hygiene to the effect of a placebo and
      to a treatment with benzodiazepines in psychophysiologic insomnia. We performed a
      clinical assay in 150 patients from a primary care unit in Chihuahua, Chih.
      Patients were allocated in three groups according to a non-systematic random
      procedure. Patients from group I received an instructive booklet with 10
      recommendations about sleep hygiene, group II received placebo, and group III
      benzodiazepines. Patients were interviewed three weeks after the maneuver was
      delivered. The effect of the maneuver was classified as success or failure. In
      Group I, the result was of 65% success vs 35% failure; in Group II. 50% success
      vs. 50% failure; and group III, 73% success vs. 23% failure (p = 0.06). In
      conclusion, all three types of treatment have similar efficacy in the management
      of insomnia. Sleep hygiene is effective and does not have risk of secondary
      effects. Thus, we recommend sleep hygiene as the therapy of first choice for
      insomnia.

PMID- 9172986
TI  - [Research on the medical historical record during the siege of Queretaro, 1867].

PMID- 9172988
TI  - [Opacification of the hepatic circulation (1947-1948). A Mexican priority].

PMID- 9172987
TI  - [The heparin treatment of toxic epidermal necrolysis. A Mexican priority].

PMID- 9172989
TI  - [Pseudopapilledema].

PMID- 9172990
TI  - [Mutant adenoviruses. A new anticancer strategy].

PMID- 9172991
TI  - [Melatonin in psychiatry].

PMID- 9172992
TI  - [The management of biologically infectious residues in a health institution: the
      Salvador Zubiran National Institute of Nutrition].

PMID- 9172993
TI  - [The National Medical Arbitration Commission and the quality of care].

PMID- 9172995
TI  - [Consensus development conference. Hepatitis C: Screening and Treatment. Paris,
      France, 16-17 January 1997].

PMID- 9172994
TI  - ["The Use and Control of Stress". A program applied to workers of the IMSS.
      Instituto Mexicano del Seguro Social].
AB  - Stress, is considered to be a bodily response to both internal and environmental
      stimuli, is a live and unavoidable energy. It is important and necessary to learn
      to use it beneficially. In order to determine the utility of the educational
      program. "The use use and control of stress", a quasi-experimental study was
      conducted in 1993, in which 39 voluntary Zone I General Hospital (IMSS Tlaxcala
      State Delegation) workers were selected, based on stress levels over 3 points as
      found in an institutional validated to measure the stress level. Five groups were
      set up, and eight weekly educative interventions, composed of cognitive contents
      including stress, relaxation techniques, and techniques for living of 90 minutes
      each were attended by the members of these groups, utilizing groups dynamics. The
      results were analyzed in simple absolute and relative frequencies, as well as by
      Student's t tests. They show a reduction stress levels in 94.8% of the
      participants, which represents a 69.1% general gain, with p = < 0.005. The
      conclusion is that learning related with the use and control of stress is an
      alternative to improve the mental health of the individual and as concerns the
      work environment, to modify attitude of the IMSS worker.

PMID- 9172996
TI  - Natriuretic peptides: are these new links in the hepatorenal connections?

PMID- 9172997
TI  - Apoptotic and antiproliferative effects of gemcitabine and gemcitabine plus Ara-C
      on blast cells from patients with blast crisis chronic myeloproliferative
      disorders.
AB  - BACKGROUND: Blast phase of chronic myeloid leukemia (CML) as well as the rare
      acute transformation of other chronic myeloproliferative disorders constitute
      forms of leukemia that are particularly refractory, even to aggressive
      chemotherapy. Many attempts have thus been made to identify new drugs that could
      be active in these diseases. We wanted to evaluate whether gemcitabine (dFdC), a
      pyrimidine analogue widely employed in lung cancer chemotherapy, was able to
      block in vitro proliferation of bcr/abl-positive and bcr/abl-negative blast cells
      in primary culture. We already showed that gemcitabine is active in inhibiting
      proliferation and inducing apoptosis of HL60 cells. METHODS: We studied the
      influence of dFdC on the proliferative potential of blasts by means of tritiated
      thymidine uptake, colony formation in semisolid medium and cell cycle parameters
      at flow cytometry. The efficacy of dFdC in inducing apoptosis was evaluated by
      flow cytometry (A0 peak) and by DNA agarose gel electrophoresis. RESULTS: We
      demonstrated that dFdC already inhibits tritiated thymidine uptake at doses of 10
      microM after 72 hours of culture, and that this effect is dose dependent. The
      addition of Ara-C 5 microM in the culture medium of dFdC provoked a synergistic
      inhibitory effect. Consistent results were obtained when cell cycle distribution
      was studied. In fact, cell incubation in the presence of dFdC resulted in a
      significant decrease of cells in S phase, although with a certain heterogeneity
      among cases. The antileukemic activity of dFdC appeared to be specific since it
      was mediated through apoptosis. We could demonstrate the appearance of the pre-G1
      apoptotic peak at cytofluorimetric analysis, and the characteristic DNA
      fragmentation pattern at agarose electrophoresis in all 10 cases after treatment
      with different doses of dFdC. Induction of apoptosis was maximal for the highest
      doses of dFdC (100 mM) and for the combination of dFdC and Ara-C. INTERPRETATION
      AND CONCLUSIONS: Following incubation with Gemcitabine leukemic blasts from
      chronic myeloproliferative disorders are induced to accumulate intracytoplasmatic
      and nuclear Ara-C and undergo apoptosis. These observations suggest that
      gemcitabine could be considered a candidate drug, capable of being used in
      polychemotherapy of refractory acute phase chronic myeloproliferative disorders.

PMID- 9172998
TI  - [Inhibitory neuronal control of smooth muscle activity of the gastrointestinal
      tract].
AB  - Recent findings suggest that nonadrenergic inhibitory responses of the smooth
      muscle of the gastrointestinal tract is mediated by nitric oxide and some
      intestinal peptides including VIP, PACAP and CGRP. Although nitric oxide was
      suggested to mediate the nonadrenergic relaxation in various regions of
      gastrointestinal tracts of many species, further careful studies revealed that
      nitric oxide participates in the relaxation in restricted regions, not throughout
      the tract. It was also found that the peptides work in extremely restricted
      regions of the tract. Importance of the role of nitric oxide in the relaxation
      varies with different regions, strains and species. Moreover, it significantly
      decreases with the age of the rat, especially between 4-8 weeks of age.
      Inhibitors of Ca(2+)-activated K+ channels inhibited the relaxation in almost all
      regions examined in rats, although the magnitude of the inhibition varied from
      region to region. The intracellular action mechanism(s) of nitric oxide was
      discussed in relation to changes in cyclic GMP level, intracellular Ca2+ level
      and membrane potentials of the smooth muscle cells.

PMID- 9172999
TI  - [Techniques for purification of rabbit osteoclasts and analysis of their
      functions].
AB  - In the process of bone remodeling or modeling, the balance between bone formation
      and bone resorption maintains normality of function and structures of bone. Major
      bone-resorbing cells, osteoclasts, are terminally differentiated from
      hematopoietic stem cells and multinucleate cells. However, direct effects of
      osteotropic factors on osteoclast function have been unclear. Attempts to obtain
      isolated mammalian osteoclasts of high purity have been unsuccessful so far.
      Initially we succeeded in isolating osteoclasts of high purity using tissue
      culture dishes because of their high affinity for the tissue culture dishes, but
      the shortcoming of this method is that it was impossible to detach osteoclasts
      from the dishes. Therefore, we could not estimate bone-resorbing activity of
      mature osteoclasts on mineralizing substratum without any influence of bone-cells
      other than osteoclasts. Recently we developed a method to avoid the defect in the
      above-described method by the use of collagen gel. Our new method may shed new
      light on our understanding of the cellular and molecular mechanisms of
      osteoclasts.

PMID- 9173000
TI  - [Pharmacological studies of BX661A. 5-[4-(2-carboxyethylcarbamoyl)-phenylazo]
      salicylic acid disodium salt dihydrate (1). Therapeutic effects on dextran
      sulfate sodium (DSS)-induced ulcerative colitis (UC) model in rats].
AB  - In the present study, we investigated the therapeutic effects of 7- or 14-day
      treatment with BX661A or salazosulfapyridine (SASP) in the DSS-induced UC model
      in rats. BX661A (10-300 mg/kg, p.o.) dose-dependently decreased the erosion area
      and the shortening of the large intestine. On the other hand, SASP (30 and
      100.mg/kg, p.o.) dose-dependently decreased the erosion area in the treatment for
      14 days (on the contrary, % inhibition of erosion area was reduced by the dose of
      300 mg/kg), but did not improve the shortening of the large intestine. Secondly,
      we investigated the therapeutic effects of 5-aminosalicylic acid (5-ASA), 4
      aminobenzoyl- beta-alanine (4-ABA) and sulfapyridine (SP) by intrarectal
      administration on the DSS-induced UC model in rats. 5-ASA significantly decreased
      the erosion area in the large intestine and improved the length of the large
      intestine of rats that was shortened by ingesting DSS. On the other hand, 4-ABA
      and SP improved neither the shortening nor the erosion area of the large
      intestine. These results suggest that BX661A may be clinically effective and
      useful in the treatment of patients with ulcerative colitis. Furthermore, it was
      suggested that 5-ASA may be the active moiety for the therapeutic effects of
      BX661A and SASP.

PMID- 9173001
TI  - Antifungal properties of yam (Dioscorea alata) peel extract.
AB  - The extraction of natural antifungal compounds from the peels of yam (Dioscorea
      alata) and the effect of these compounds on both the vegetative and reproductive
      structures of some yam not pathogens were studied. Four prominent antifungal
      components were obtained; one of the components was fully characterized and
      identified as beta-sitosterol. The antifungal activity of the compounds toward
      the germination of spores of two yam pathogens showed an inhibition of less than
      57% at a concentration of 50 mg/L while inhibition on the elongation of germ
      tubes of Fusarium moniliforme was as high as 82% at the same concentration.
      However, the ED50 for inhibition of germ-tube elongation in the yam compounds for
      the same organism was below 32 mg/L. The role of the yam compounds at high
      concentrations in disease resistance is discussed.

PMID- 9173002
TI  - [Growth factor allows longer survival in HIV patients].

PMID- 9173003
TI  - [Hepatitis B vaccination--an interdisciplinary responsibility].

PMID- 9173004
TI  - [Recent antithrombotic gold standard?].

PMID- 9173005
TI  - [Antibiotics--how do I administer them to my child?].

PMID- 9173006
TI  - [Rheumatoid arthritis. Begin early aggressive therapy].

PMID- 9173007
TI  - [Renovascular hypertension. The most common curable form of hypertension and
      chronic renal failure].
AB  - Some 20% of the adult population suffer from high blood pressure, the great
      majority having essential hypertension, that is, elevated blood pressure for
      which no specific cause can be found. Only about 5% of hypertensives present with
      secondary hypertension, that is, they have a specific, often treatable disease of
      which raised blood pressure is one, frequently the leading symptom. The
      renovascular disease is responsible for roughly one half of these cases.

PMID- 9173008
TI  - [Renal hypertension. Renovascular and parenchymatous hypertension--from clinical
      suspicion to therapy].

PMID- 9173009
TI  - [What is the benefit of the new AT1 receptor antagonists?].

PMID- 9173010
TI  - [Only early invasive therapy can be curative. Interview by Dr. rer. nat. Anita
      Schweiger].

PMID- 9173011
TI  - [Hypoglycemia. Symptoms, differential diagnosis, therapy].
AB  - Hypoglycemia is often associated with typical, but not specific symptoms. A
      differentiation is made between neuroglucopenic symptoms (e.g., confusion,
      somnolence) on the one hand, and those that arise as a result of the
      counterregulatory response of the sympathetic nervous system (e.g., tremor,
      sweating), on the other. The diagnosis of hypoglycemia can cause considerable
      problems, in particular when only isolated single symptoms present (e.g.,
      confusion, psychosis, seizures, coma). For the elective clarification of
      recurrent hypoglycemia, further diagnostic examinations (e.g., fasting with
      determination of hormones, measurement of insulin) are employed in addition to
      the patient's history. For differential diagnostic considerations not only
      organic causes, but also adverse drug reactions and a factitious genesis must be
      excluded. In the event of an emergency (e.g., hypoglycemic coma) the usual form
      of treatment is the administration of glucoses or glucagon.

PMID- 9173012
TI  - [Infection of the urogenital tract. 2: Diagnosis in urinary tract infections-
      general diagnosis].

PMID- 9173013
TI  - [Epileptic seizures in children: acupressure instead of diazepam!. Interview by
      Elisabeth Moosmann M.A..].

PMID- 9173014
TI  - [Conservative management of alcohol intoxicated patients].

PMID- 9173015
TI  - [Children fleeing from life].

PMID- 9173016
TI  - [Premenstrual syndrome: does gamma-linolenic acid help?].

PMID- 9173017
TI  - ["Water in the lungs is quickly resorbed"].

PMID- 9173018
TI  - [Is the anxiety about Ecstasy justified?].
AB  - "Ecstasy", that is, MDMA and its analogues are derivatives of amphetamine. In
      consequence of its neurotoxicity, it can be acutely life-threatening, and can
      also have injurious long-term effects. A major role in its noxious effects is
      played by disorders in the serotonergic system and degeneration, in part
      irreversible, of serotonergic neurones (demonstrated in animals). Its, most
      youthful, users need to receive proper information that emphasizes rather than
      playing down its harmful effects.

PMID- 9173019
TI  - [Stroke and intracranial hemorrhage after cocaine abuse].
AB  - Cocaine abuse as a risk factor for acute cerebrovascular events has received too
      little attention, in particular in young patients. Cocaine hydrochloride causes
      mainly intracerebral and subarachnoidal bleeding, while crack (freebase) causes
      intracranial hemorrhage and ischemic infarctions with equal frequency. Although
      no specific antidote is known, an attempt should be made to detect the substance
      or its metabolites in the urine so as to provide optimal management, and
      encourage the patient to seek expert counselling.

PMID- 9173020
TI  - [Alcohol, street drugs and therapeutic drugs in street traffic].
AB  - While the rigorous prosecution of drunken drivers in Germany has resulted in a
      decrease in alcohol related accidents since the 1990s, the relevant risks of
      legal or illegal drugs are still receiving too little attention, and legal
      proceedings are rare. A study carried out at the beginning of the 1990s and data
      from a roadside survey in two distinct regions of Germany (Franken and Thuringen)
      show that the effect of illegal drugs and medications is almost equally as
      important as those of alcohol. A new bill proposes a general ban on driving under
      the influence of drugs, both legal and illegal. A major problem, however, is the
      need to show drug/medication misuse and recognize the specific symptoms in the
      individual case-only then successful use can be made of already existing legal
      remedies.

PMID- 9173021
TI  - ["Nice young people looking for fun". Interview by Dr. rer nat. Anita Schweiger].

PMID- 9173022
TI  - [Other countries, other drug abuse? Drug dependence and approaches for
      controlling drug abuse as a global issue].

PMID- 9173023
TI  - [Infections of the urogenital tract. 3: General and organ specific diagnosis in
      urinary tract infections].

PMID- 9173024
TI  - [How can diabetic retinopathy be therapeutically modified? Advanced glycosylation
      end products (AGEs) and hyperglycemic memory].

PMID- 9173025
TI  - [General practice 2000--what should be done today?. Interview by Dr. Till Uwe
      Keil].

PMID- 9173026
TI  - [First surf tour on the Internet. Closed services for physicians are in the midst
      of a barely manageable flood of information].

PMID- 9173027
TI  - [Inguinal hernia--which method leads to the goal? Endoscopic and open surgical
      procedures are available].
AB  - In recent years, the methods available for repair of inguinal hernia have greatly
      expanding, resulting in confusion as to what constitutes a suitable choice. Is it
      to be laparoscopy or open surgery, plastic mesh yes or no, general anesthesia or
      local anesthesia? Bassini's operation has now been ousted by the Shouldice
      procedure, which is suitable for all primary forms of hernia. The Lichtenstein
      procedure is readily and rapidly carried out under local anesthesia, making it
      suitable for use in multimorbid and old patients; the recurrence rate is low. The
      laparoscopic approach can be recommended for patients who, for private or
      occupational reasons need to be up and about again as soon as possible. It is
      also particularly suitable for the treatment of recurrent hernias or for the
      simultaneous repair of bilateral hernias. Disadvantages are the high costs, a
      lack of long-term results and unusual complications that are not seen in open
      surgery.

PMID- 9173028
TI  - [Abdominal surgery--value of endoscopic interventions. For which indications is
      laparoscopic procedure the standard already today?].

PMID- 9173029
TI  - [Inguinal hernia operation in the manuscript "Practica Copiosa". Serial
      presentation of surgical steps by the Lindau surgeon Caspar Stromayr (1559)].

PMID- 9173030
TI  - [The patient must depend on the advice of the surgeon. Prof. Dr. med. K.-W.
      Jauch, Regensburg, on endoscopic operation of inguinal hernia. Interview by Dr.
      rer. nat. Anita Scheiger].

PMID- 9173031
TI  - [Diagnostic strategies in rheumatology. 1: Clinical diagnosis--steps 1 and 2].

PMID- 9173032
TI  - [Because of its complications prevention is vital. Hepatitis B vaccination is
      available even for infants. Interview by Dr. Rolf Rolf-Gunther Sommer].

PMID- 9173033
TI  - [Pharmacotherapy of Alzheimer dementia: therapy of cognitive symptoms--new
      results of clinical studies].
AB  - Recent investigations have given new insights into pathogenetical determinants of
      Alzheimer's disease. Amyloid deposition and neurofibrillary tangles are no longer
      considered to be primary pathological changes. Neurobiological research tries to
      work out the etiopathogenital cascade that finally causes Alzheimer's disease. So
      far, several relevant pathogenetical factors have been detected, e.g. pertubated
      control of glucose breakdown, impairment of oxidative metabolism, impaired
      neuroprotection due to increased oxidative stress and non-enzymatic protein
      glycation as well as immunological disturbances. Thus, new strategies for the
      development of cognition-enhancing drugs are emerging. The authors review reports
      on agents, that are under investigation for the treatment of cognitive
      symptomatology in Alzheimer's disease. Some of these agents have already been
      used for treatment of other medical conditions, e.g. nimodipine, memantine as
      well as selegiline. Many of them are still experimental. Promising strategies
      include antioxidative agents (e.g. vitamin E, vitamin C, beta-carotin),
      acetylcholinesterase-inhibitors with central selectivity (e.g. ENA 713), M1- and
      M4-muscarinic receptor agonists (milameline) as well as sabeluzole, a
      benzothazide derivative that shows neurotrophic activities and anti-inflammatory
      substances like indomethacin.

PMID- 9173034
TI  - [Nondeclarative memory--neuropsychological findings and neuroanatomic
      principles].
AB  - The contents of long-term memory will influence behaviour, even if the acquired
      knowledge or the original learning episode are not remembered. These phenomena
      have been termed "non-declarative" or "implicit" memory, and they are contrasted
      with "declarative" or "explicit" memory which is characterised by conscious
      search and retrieval procedures. Non-declarative memory encompasses non
      associative learning, simple conditioning, priming effects as well as motor,
      perceptual and cognitive skill acquisition. The dissociation of both forms of
      memory is documented by studies in health subjects which indicated that
      experimental manipulations or drugs may differentially affect declarative and non
      declarative memory processes. Damage to the medial temporal or the medial
      thalamic regions is known to result in declarative memory deficits whereas non
      declarative memory is largely unaffected by such lesions. Animal research and
      clinical findings indicate that several components of non-declarative memory such
      as motor and cognitive skill acquisition or certain types of classical
      conditioning are dependent upon the integrity of the basal ganglia or the
      cerebellum. These issues are therefore of increasing importance for the
      understanding of extrapyramidal and cerebellar diseases. This paper presents
      recent neuropsychological findings and neuroanatomical data relating to the issue
      of non-declarative memory.

PMID- 9173035
TI  - [Psychological, psychotherapeutic and other non-pharmacologic forms of therapy in
      treatment of insomnia. Position of the "Insomnia" Study Group of the German
      Society of Sleep Research and Sleep Medicine].
AB  - Psychological and psychotherapeutic techniques are an essential part of the
      treatment of insomnia. Mainly two facts stress the importance of
      psychological/psychotherapeutical strategies for insomnia: (1) Concepts for non
      drug treatment aim at improvement of the symptoms and the underlying cause of the
      disease and (2) disadvantages of hypnotic therapy such as substance abuse or
      addiction are avoided. Effective treatment techniques such as patients education
      and counseling, sleep hygiene, stimulus control and relaxation techniques should
      be known to every therapist, especially general practitioners who treat the
      majority of patients haring difficulties in initiating or maintaining sleep.
      Several other effective behavioural techniques, e.g. sleep restriction, or
      cognitive therapy, and psychotherapy should be used only by skilled and trained
      experts. Insomniacs with chronic and severe complaints should be treated by
      therapists with experience in sleep medicine. Multimodal treatment strategies are
      provided for by sleep disorder centres and combine effective treatment elements
      in structured therapeutic concepts. There is absolute consensus of opinion that
      every hypnotic treatment of an insomniac patient should be combined with basal
      elements of non-drug treatment strategies.

PMID- 9173036
TI  - [Psychiatric disorders and illnesses after childbirth].
AB  - After childbirth, from about a quarter up to nearly one half of all puerperae
      develop a short-lasting, mild affective distress, the so called blues. During the
      first months after delivery, about 10-15% of all young mothers suffer from a
      longstanding depression which is so severe that they are in need of treatment. In
      one or two out of 1000 women even a psychotic disorder becomes manifest. These
      postpartal disturbances and diseases are often not diagnosed by doctors-on the
      one hand because the women concerned often hide their complaints due to shame and
      a sense guilt regarding their supposed failure as a good mother, on the other
      hand because these syndromes until now have not found enough attention in German
      as opposed to Angloamerican-medicine. Yet, these disorders-apart from the blues
      are very serious ones with potentially severe consequences for the mother, the
      baby and possibly the whole family. Women with mental disorders in their family
      history and especially their own history are at an increased risk. They should be
      informed about this and, in certain cases, be treated preventively. Women with
      depressive and psychotic disorders are, especially in the postpartal time, in
      urgent need of treatment which, depending on type and severity of the disorder,
      should consist of psychotherapy, frequently also pharmacotherapy, and social
      care. Special needs of the postpartal period such as breast-feeding or the mother
      infant relationship have to be considered which often requires close cooperation
      of the psychiatrist/psychotherapist, the gynaecologist and the pediatrician.

PMID- 9173037
TI  - [Acetaminophen poisoning].

PMID- 9173040
TI  - Thermal resistance parameters of the air environment at various altitudes.
AB  - The thermal properties of atmospheric air surrounding the human body at various
      altitudes are characterized with a system of parameters. This system comprises
      resistance of the air to convective heat transfer h(c)(-1), degrees C (W/m2)(-1)
      and to water vapour transfer h(D)(-1), s/m. The concept of 'evaporative
      resistance' h(e)(-1), hPa (W/m2)(-1) following the similarity of the processes is
      introduced. In obtaining the altitude dependencies of investigated parameters, a
      respective heat transfer equation expressing the rate of heat exchange at the
      boundary body surface-ambient air is applied. The use of the body thermal state
      of the established attitude dependencies is discussed. The concept of 'thermal
      stability' related to the evaporative resistance parameter h(e)(-1)is introduced.
      This parameter is assumed as: (1) an indicator of the human body thermal
      stability and (2) distributor and predictor of environmental influence on the
      body thermal state.

PMID- 9173038
TI  - [Examination of myocardial perfusion with positron emission tomography: a
      clinically useful and valid method?].
AB  - Positron emission tomography (PET) of the heart has gained widespread scientific
      and clinical acceptance with regard to 2 indications: 1. the detection of
      perfusion abnormalities by qualitative and semiquantitative analyses of perfusion
      images at rest and during physical or pharmacological stress using well validated
      perfusion tracers such as N-13 ammonia, Rb-82 rubidiumchloride, or O-15 labeled
      water, 2. Viability imaging of myocardial regions with reduced contractility by
      combining perfusion measurements with substrate metabolism as assessed from F-18
      deoxyglucose utilization. This overview summarizes the use of PET as a perfusion
      imaging method. With a sensitivity > 90% in combination with a high specificity,
      PET is today the best available nuclear imaging technique for the diagnosis of
      coronary artery disease (CAD). The short half-life of the perfusion tracers in
      combination with highly sophisticated hard- and software enables rapid PET
      studies with high patient throughput. The high diagnostic accuracy and the
      methological advantages as compared to conventional scintigraphy allows to use
      PET perfusion imaging for detection of subtle changes of the perfusion reserve
      for detection of CAD in high risk but asymptomatic patients as well as in
      patients with proven CAD undergoing various treatment forms such as risk factor
      reduction or coronary revascularization. In patients following orthotopic heart
      transplantation, evolving transplant vasculopathy can be detected at an early
      stage. Quantitative PET imaging at rest allows for detection of myocardial
      viability since cellular survival is based on maintenance of a minimal perfusion
      and structural changes correlate to the degree of perfusion reduction.
      Furthermore, quantitative assessment of the myocardial perfusion reserve detects
      the magnitude and competence of collaterals in regions with occluded epicardial
      arteries and thus, imaging of several coronary distribution territories in one
      noninvasive study. The cost of PET in combination with the cost of a cyclotron
      facility together with the demanding methological problems have limited the
      availability of PET to a few but sophisticated centers. Therefore, quantitative
      PET investigations have been performed predominantly for scientific purposes and
      the cost-effectiveness of PET in the everyday clinical setting is not yet finally
      proven. However, the unique possibilities of PET to study noninvasively and
      quantitatively myocardial perfusion and metabolism as well as cardiac innervation
      and pharmacokinetics of cardiac drugs have established cardiac PET as a
      scientific tool of highest quality for the future.

PMID- 9173039
TI  - [Torsade de pointes tachycardia during administration of quinidine and verapamil
      in atrial fibrillation].
AB  - The following case report shows that life threatening arrhythmias with fatal
      consequences may occur after treatment with Cordichin a combination of 80 mg
      verapamil and 160 mg quinidine. A 65-year-old woman was treated with Cordichin
      due to atrial fibrillation lasting for 3 months. After the first day of treatment
      the patient suddenly collapsed with loss of consciousness. The patient was
      resuscitated 15 min later. The emergency physician diagnosed a cardiac arrest.
      After cardiopulmonary resuscitation and intubation stable circulation was
      restored. When the patient was admitted in our hospital the ECG showed numerous
      ventricular extrasystoles, marked prolongation of the QT interval (700 ms)
      (Figures 1a and b) and nonsustained polymorphic ventricular tachycardias (Figure
      2). The arrhythmias could be suppressed by right ventricular stimulation after
      inserting a pacemaker lead. After a period of 12 h a normal QT interval was
      restored (Figure 3). Unfortunately the patient died 3 days later due to
      irreversible cerebral damage. The concept of suppressing proarrhythmic effects of
      quinidine by calcium antagonists is discussed. Despite theoretical advantages of
      a combination therapy this case report shows that life threatening dysrhythmias
      cannot be prevented by additional calcium antagonism.

PMID- 9173041
TI  - [Etiology of obesity].

PMID- 9173042
TI  - [Obesity. Increased mortality caused by arteriosclerotic sequelae and
      carcinomas].

PMID- 9173043
TI  - [Obesity and type ii diabetes mellitus].

PMID- 9173044
TI  - [Obesity and lipid metabolism disorders].

PMID- 9173045
TI  - [Obesity and hypertension].

PMID- 9173046
TI  - [Strategies in therapy of obesity].

PMID- 9173047
TI  - [17-year-old patient with whole body erythema, fever, compensated renal failure,
      thrombocytopenia and increase creatine kinase. Toxic shock syndrome].

PMID- 9173048
TI  - [66-year-old man with an unusual anastomosis ulcer after Billroth II stomach
      resection].

PMID- 9173049
TI  - [Anticoagulation of cerebral infarct].

PMID- 9173050
TI  - [Thrombophlebitis--use of vitamin K antagonists].

PMID- 9173051
TI  - [Dosage of acetylsalicylic acid in cerebral ischemia].

PMID- 9173052
TI  - [Selective cyclooxygenase-2 (COX-2) inhibitor. Progress in rheumatoid therapy?].

PMID- 9173053
TI  - [Chronic hepatitis].

PMID- 9173054
TI  - [Therapy studies in dermatologic oncology. Recommendations for patient
      education].
AB  - Guidelines of good clinical practice regulate controlled clinical studies. Goal
      of the study, type of treatment and possible side effects have to be explained.
      The physician faces problems, if the study includes a "no treatment group".
      Referring to the literature and based on our own experience with tumor patients,
      several criteria are proposed to optimize the recruitment of patients. Important
      points are: Explanations should be given by an experienced doctor. He must be
      informed about the study and therapeutic alternative treatments. The atmosphere
      for the talk must be quiet. The participation of a person whom the patient trusts
      is desirable. The necessity of the study must be explained. Randomization in
      different study groups should be discussed without any preference. Prognosis
      should be explained without any detailed statistical data. Form of treatment,
      possible side effects and control examinations have to be discussed. The family
      physician's cooperation should be stressed. Personal autonomy in the patient's
      decision to participate in the study must be emphasized. Enough time for
      reflection must be granted before the final decision. It must be assured that the
      patient receives the same medical attention even after rejecting the study. These
      recommendations might help to avoid major mistakes which are harmful for the
      doctor-patient-relationship and further tumor therapy. A good initial discussion
      forms the basis for effective cooperation during tumor treatment. It may
      counteract the personal fear and negative reports in media of being "a guinea
      pig". The patient will appreciate the efforts of the doctor to provide optimal
      therapy. Furthermore, he will realize that such studies are necessary to improve
      future therapies.

PMID- 9173055
TI  - [Mollusca contagiosa in HIV infection. Clinical manifestation, relation to immune
      status and prognostic value in 39 patients].
AB  - Mollusca contagiosa predominantly affect children; their occurrence in adults is
      rare. In recent years many descriptions of mollusca contagiosa in
      immunosuppressed patients, mostly in HIV-infected individuals, have appeared. We
      analysed the occurrence of mollusca contagiosa in a large group of HIV-patients
      and examined their relation to the immune status and their prognostic
      significance. 456 patients with HIV-associated skin disorders were documented in
      the HIV follow-up clinics at the Department of Dermatology, University Medical
      Center Benjamin Franklin, Berlin, during the years 1982-1992. Molluscum
      contagiosum was diagnosed in 39 patients (8.6%). 38 of the 39 patients were
      homosexual and/or bisexual men. The median age of the patients was 34 years.
      Large, papular and nodular lesions up to 1 cm in diameter were observed in some,
      individuals. Frequently, multiple lesions in atypical localizations such as the
      face were found. Significant immunosuppression was present in the majority of
      patients with mollusca contagiosa at the time of their first diagnosis; median
      CD(4+)-T-lymphocyte count was 122/microliter and the median CD4+/CD(8+)-ratio was
      0.2. The median survival time was 12 months in patients with mollusca contagiosa.
      There was no significant difference between the prognosis of patients with
      mollusca contagiosa and other HIV-infected patients showing similar reduction of
      their immune status. Our study showed that mollusca contagiosa are a rather
      frequent infection in HIV-patients. Mainly localized to the face, they are easily
      diagnosed and may serve as an excellent clinical marker for recognizing advanced
      immunosuppression in HIV-infection. Survival prognosis of patients with molluscum
      contagiosum is unfavourable, corresponding to their reduced immune status. The
      presence of mollusca, however, is not an independent prognostic marker, if the
      immune status is considered.

PMID- 9173056
TI  - [Secondary wound healing with reference to anatomic subunits in operations of the
      mid-facial area].
AB  - The healing of wounds by secondary intention is a simple method to close
      operative defects. The quality of wound healing will depend on the anatomic site
      on the face as well as on size and depth of the defect. Best functional and
      cosmetic results are obtained at locations with concave geometry and when the
      defect lies symmetrically at the interface of two anatomic subunits. Partial
      reconstruction or guiding sutures can create a symmetric defect in relation to
      anatomic subunits which will heal by second intention. This simple and efficient
      operative procedure is illustrated by two case reports.

PMID- 9173057
TI  - [Erythema elevatum diutinum. A rare dermatosis with a broad spectrum of
      associated illnesses].
AB  - Erythema elevatum diutinum (EED) is a rare disease presenting with persistent red
      to yellow-brown papules or plaques which are mainly localized symmetrically on
      the extensor aspects of the hands and fingers, the elbows and the knees. The
      histology shows a leucocytoclastic vasculitis in early lesions and fibrosis of
      the dermis later on. Dapsone is the treatment of choice. Today, EED is usually
      assigned to the neutrophilic dermatoses in which an association with
      hematological disturbances is well documented. We report on a patient with EED
      and glioma WHO grade IV, a coincidence unreported hitherto. Additionally, we
      review the literature on diseases associated with EED.

PMID- 9173058
TI  - [Generalized Mycobacterium avium-intracellulare infection due to
      immunosuppressive therapy of paraneoplastic dermatomyositis].
AB  - The ubiquitous Mycobacterium avium-intracellulare (MAI) is the most frequent
      cause of disseminated atypical mycobacteriosis in AIDS patients. MAI infections
      may develop in patients with other acquired immune defects, such as connective
      tissue disorders. In adults, the gastrointestinal and respiratory systems are
      most frequently affected. We report a patient with dermatomyositis receiving
      immunosuppressive therapy in whom only the skin and the skeletal system were
      affected by MAI. Because it presented with polymyositis-like symptoms, the
      infection was initially not identified and treated. The MAI was cultured from a
      periarticular joint effusion from the right upper arm and from venous blood, as
      well as identified histologically in lesional skin. Resistance to antibiotics
      developed most likely because the patient failed to take oral antibiotics
      regularly. Because of an acute exacerbation of the tumor-associated
      dermatomyositis, immunosuppressive therapy was initiated, while the
      tuberculostatic therapy was continued. Using these therapies both diseases
      markedly improved. In patients with connective tissue disorders receiving
      longterm immunosuppressive therapy, especially when changes in symptoms and signs
      are observed, opportunistic infections such as MAI should be considered and
      included in the differential diagnosis.

PMID- 9173060
TI  - [Bullous mastocytosis in a child].
AB  - We report a case of bullous mastocytosis in a 30-month-old girl, who developed
      disseminated pruritic urticarial and bullous lesions on the trunk accompanied by
      episodes of vomiting and generalized flushing. Her problems began at the age of 6
      months. Her stool was repeatedly positive for occult blood. Histamine and 5
      hydroxytryptamine were measured in the urine and serum; urine 5-hydroxytryptamine
      levels were elevated. In addition, trypsin and chymotrypsin levels were raised in
      the blister fluid. Metachromatic staining of the mast cells in a skin biopsy
      specimen confirmed the diagnosis. A combination of oral disodium cromoglycate and
      ketotifen produced a dramatic improvement of the cutaneous and gastrointestinal
      features.

PMID- 9173059
TI  - [Superior vena cava syndrome. Description of 3 cases and review of the
      literature].
AB  - Superior vena cava syndrome (VCSS) develops because of a progressive reduction of
      venous return from the head, neck and the upper extremities. The presenting sign
      of this relatively rare condition is often a rapidly developing, often massive
      facial edema. As a consequence, such the patients are often seen initially by a
      dermatologist. Other clinical characteristics may include cyanotic facial
      erythema, dilatation of the neck veins, and a prominent venous pattern n the
      anterior chest. Today, primary lung cancers and other mediastinal tumours
      represent the most common cause of VCSS, which may take a slowly progressive or a
      more fulminant course. In these cases, the disease develops rapidly and becomes
      life-threatening, requiring intensive medial diagnosis and care. We describe
      three patients with superior vena cava syndrome due to a) bronchogenic carcinoma,
      b) bihilar sarcoidosis and c) metastasizing malignant melanoma. Since recognition
      of VCSS broadens the diagnostic spectrum of the dermatologist, an overview on its
      diagnostic and therapeutic implications is given based on our cases and the
      literature.

PMID- 9173062
TI  - [Dermatology for Africa. The Regional Dermatology Training Center in Tanzania].

PMID- 9173061
TI  - [Unusual Koebner phenomenon in psoriasis caused by varicella and UVB].
AB  - An isomorphic response is defined as a nonspecific skin stimulus eliciting a
      disease-specific skin reaction. We report on the development of the Koebner
      phenomenon in a 32 year old patient with psoriasis after skin testing with UVB at
      a dose above 0.055 J/cm2. In addition we describe a 28 years old patient who
      developed new psoriatic plaques in the areas affected by the virus after a
      varicella infection.

PMID- 9173063
TI  - [Photodynamic therapy (PDT)].

PMID- 9173064
TI  - [Innovative therapy with metalloprotease inhibitors].

PMID- 9173065
TI  - [Resistance to activated protein C by mutation of the factor V gene. Most
      frequent blood coagulation defect in venous thromboses].
AB  - Deep venous thromboses, in particular when recurrent, can be associated with
      chronic venous leg ulcers. Such complications are often seen in dermatology
      departments and frequently represent a therapeutic problem. Resistance to
      activated protein C (APCR) has recently been identified as the most frequent
      coagulation defect associated with an increased risk of venous thrombosis. In
      most cases, APCR is caused by a point mutation in the factor V gene which results
      in an impaired inactivation of activated factor V (Va). As a consequence of this,
      an important anti-coagulant mechanism in the physiological balance of the
      hemostatic system is abolished. This autosomal dominantly inherited genetic
      defects affects about 5% of the general population. In this article we draw
      attention to the existence of this recently identified, genetically determined
      risk factor for venous thrombosis, describe recent diagnostic developments and
      discuss therapeutic options.

PMID- 9173066
TI  - [Cream PUVA photochemotherapy].
AB  - Bath-PUVA-photochemotherapy lacks systemic side effects and requires low
      cumulative UVA doses, but a major disadvantage is the logistical requirement for
      bath tubs in a practice. We have developed an alternative form of topical PUVA
      therapy using a lipophilic emulsion vehicle for the photosensitizer 8-MOP (cream
      PUVA-photochemo-therapy). A 0.0006% 8-MOP containing water-in-oil emulsion (30%
      H2O) was optimal for inducing photosensitivity in treated skin areas without
      increasing 8-MOP plasma levels. Increased skin photosensitivity was maximal 1
      hour after cream application and persisted for 3 hours. We next assessed the
      effectiveness of cream-PUVA-photochemotherapy in the treatment of patients with
      chronic recalcitrant palmoplantar eczema (n = 10). In seven patients complete,
      and in two patients partial, remissions were observed after 40 treatments. Thus,
      cream-PUVA-photochemotherapy, which is easier to perform than bath-PUVA
      photochemotherapy, is an effective, safe and low-cost modality, which may prove
      to become the topical PUVA therapy of choice for dermatological practitioners.

PMID- 9173067
TI  - [Characterization of nonresponders in high dosage UVA1 therapy of acute
      exacerbated atopic dermatitis].
AB  - High-dose UVA1 therapy is an effective treatment of patients with acute atopic
      dermatitis. However, some patients do not respond well to this new therapy. We
      attempted to further characterize the non-responder population in a retrospective
      study. Two closely matched groups of responders (n = 20) and non-responders (n =
      20) were compared. No significant differences were observed between both groups
      with respect to the following parameters: skin type, minimal erythema dose,
      single and cumulative doses of UVA1, and peripheral blood eosinophils. However,
      non-responders were characterized by a highly elevated atopic score, and by high
      levels of total IgE and of specific IgE. Furthermore, colonization of the skin
      with Staphylococcus aureus occurred at higher densities, and intestinal growth of
      Candida albicans was more frequently observed. These data indicate that high-dose
      UVA1 irradiation is not effective in all patients suffering from atopic
      dermatitis. We conclude that non-responders with complicating infections might
      benefit from the combination of high-dose UVA1 therapy and antibiotic or
      antimycotic treatment.

PMID- 9173068
TI  - [Immune tolerance of skin xenotransplants].

PMID- 9173069
TI  - [Primitive medicine and high tech medicine].

PMID- 9173070
TI  - [Treatment of tinnitus with lidocaine?].

PMID- 9173071
TI  - [3D computer-assisted ENT biopsies of the Iceman].
AB  - The University of Innsbruck possesses a unique prehistoric, completely conserved
      5300-year-old human cadaver. We report our experiences during which ENT
      specialists collected samples from various cavities inside the Iceman. Guidance
      of biopsy instruments was accomplished with computer-assisted navigation based on
      Interventional Video Tomography. This technology allows surgical guidance by
      interlinking currently available imaging modalities with live endoscopic video.
      The system operates without patient fixation and is practically free of external
      contact. Apart from sterility, special precautionary measures were necessary to
      avoid contamination with heavy metals or microorganisms. Visual inspection of the
      samples of mucosa from the nose, maxillary sinus and larynx revealed the typical
      patterns of a human cadaver without overt pathology.

PMID- 9173072
TI  - [Treatment of tinnitus with lidocaine? A report of clinical experiences].
AB  - The efficacy of intravenous lidocaine therapy in patients suffering from severe
      tinnitus aurium has been reported for many years although pharmacological
      mechanisms for its use are not fully understood. In order to evaluate the
      effectiveness of lidocaine therapy in the treatment of tinnitus we performed a
      retrospective study on 77 patients suffering from tinnitus. All patients were
      given a test dose of lidocaine after a saline placebo infusion. Suppression of
      tinnitus was classified according to a visual analogue scale. Our results showed
      that 19 of the 77 patients investigated experienced different degrees of reduced
      tinnitus. Fourteen of these latter patients also were treated with oral tocainide
      3 x 400 mg/day. Treatment was stopped in 13 of the patients because of side
      effects or an insufficient effect on tinnitus. Our findings suggest that
      lidocaine and tocainide do not have a significant role in pharmacological
      treatment of tinnitus except in certain cases of long-standing severe tinnitus.

PMID- 9173073
TI  - [Use of the ISG viewing wand on the temporal bone. A model study].
AB  - Surgical interventions in the petrous bone have to be performed in close
      relationship to vital and delicate anatomical structures. In cases of revision
      surgery or with massive pathological changes 3D computer-assisted navigation
      provides an essential tool for preoperative planning, definition of target
      structures and intraoperative orientation. This technology can help to diminish
      intraoperative risks for the patient and may help to optimize any microsurgery.
      In this report we present our first experiences in using the ISG Viewing Wand in
      the petrous bone through a specially designed model. By recording more than 4000
      single measurements we found that the ISG Viewing Wand can be used with
      sufficient precision. We have now outlined the most important conditions
      necessary for possible application to a patient.

PMID- 9173074
TI  - [A registration system for evaluating acusto-mechanical transmission of middle
      ear implants].
AB  - A measurement system was developed that permits objective comparisons of the
      sound conduction of middle ear implants. The implants are fitted into a
      mechanical middle ear model which approximates the impedances of the eardrum and
      the inner ear. A defined signal within the frequency range of 0-5 kHz is provided
      by a miniaturized loudspeaker at the input to the model and is measured by a
      probe microphone. Displacement of an artificial stapes footplate at the output of
      the model is measured by a fiberoptic probe with a sensitivity of 5 nm. The
      transmission function is calculated as the quotient of the output and the input
      signal. This system can be used to evaluate the sound-transmitting properties of
      different middle ear implants excepting other influences, such as surgical
      techniques. This work details the measurement system and demonstrates basic
      influences on the sound-transmission of middle ear implants.

PMID- 9173075
TI  - [Quality control in pediatric hearing aid fitting].
AB  - Specific hearing aid selection and careful fitting are essential for successful
      rehabilitation of hearing-impaired children. For this reason the different
      hearing aid types prescribed, the type and frequency of hearing aid
      insufficiencies reported and the effectiveness and regularity of our follow-ups
      were studied evaluating 253 followup exams in 39 children (71 ears) suffering of
      a sensorineural hearing loss, including all degrees, supplied with a behind-the
      ear hearing aid. Most of the devices had been prescribed outside our department
      on an initial trial basis. After critical evaluation, the number of hearing aid
      types was reduced from 33 to 23 when corresponding devices failed to match well
      with the degrees and types of hearing losses present. A further decrease in
      hearing aid types could not be achieved as a consequence of many being already
      end-prescribed. Insufficiencies (n = 222) were found in 60% of the hearing aid
      evaluations: 59% involved dynamic hearing aid adjustments requiring better
      amplification (37%), distortion (18%) and dynamics (4%). Additionally, 16%
      affected hearing aid function and another 16% form (9%) and material (4%) of the
      otoplasty and the tube (3%). The last 9% of the deficiencies concerned the
      potentiometer cap: it hadn't been fitted in about half of the cases and had been
      lost in the other half despite being needed. Routine followup evaluations of the
      hearing aids occurred regularly in 76% of the cases with an effectiveness of 73%.
      Our results confirm the importance and necessity for pedaudiologic qualitative
      hearing aid controls in children.

PMID- 9173077
TI  - [Irregular visual field constriction. Juvenile nasopharyngeal fibroma].

PMID- 9173076
TI  - [Simultaneous occurrence of a cystadenolymphoma (Warthin tumor) in the parotid
      gland and larynx].
AB  - Warthin's tumour of the larynx is an unusual finding. In present literature only
      four cases have been reported. Only one case of a woman suffering from Warthin's
      tumour of the parotid gland and the ipsilateral site of the larynx has been
      published. A case of a 74-year-old woman with an Warthin's tumour of the right
      parotid gland and the left false cord is presented. The theories about the
      development of Warthin's tumours are discussed.

PMID- 9173078
TI  - [Sequelae of total laryngectomy with special reference to rehabilitation of the
      voice and lower airways].

PMID- 9173079
TI  - 12th International Organization of Psychophysiology meeting and 8th World
      Congress of Psychophysiology. Tampere, Finland, 25-29 June 1996. Abstracts.

PMID- 9173080
TI  - [Diagnostic ultrasonography of perforating foreign bodies of the digestive
      tract].
AB  - Perforations of the gastrointestinal tract by ingested foreign bodies such as
      chicken or fish bones are rare and may occur at any site from the oesophagus to
      the rectum; the diagnosis is often very uneasy with conventional radiography. For
      many years, sonography has been more frequently requested as the first modality
      for the evaluation of abdominal pathology, and in many cases allowed a correct
      diagnosis to be reached without further assessment. We report six cases of
      complicated foreign bodies very successfully and specifically diagnosed by
      sonography in six different sites of the gastrointestinal tract. Four of these
      cases were preliminary correctly suspected by CT but the shape, length and the
      probable nature of the body were always better appreciated by multiaxial real
      time sonography. The correct sonographic diagnosis and follow-up allowed a
      conservative treatment in three cases, avoiding surgical exploration. We
      recommend the systematic sonographic investigation of foreign bodies in close
      relation with the gastrointestinal tract in all atypical inflammatory processes
      or to perform sonography as a complement to CT.

PMID- 9173081
TI  - Osmolarity is an independent trigger of Acanthamoeba castellanii differentiation.
AB  - Like many yeasts, bacteria, and other sporulating microorganisms, Acanthamoeba
      castellanii (Neff), a free-living amoeba with pathogenic relatives,
      differentiates into a dormant form when deprived of nutrients. Acanthamoeba cysts
      redifferentiate into trophozoites when food is resupplied. We report here that
      Acanthamoeba encystment is also triggered by elevated osmolarity, and that
      osmolarity and cell surface receptor binding are synergistic in triggering
      differentiation. Additions of sodium chloride or glucose to rich growth media
      were used to produce specific osmolarity increases and similar encystment results
      were obtained with either additive. Although many organisms, including
      Acanthamoeba and mammalian cells, have been shown to adapt to hyperosmolar
      conditions, this is the first demonstration that hyperosmolarity can be a primary
      differentiation signal.

PMID- 9173082
TI  - Normal and transforming Ras are differently regulated for posttranslational
      modifications.
AB  - Point mutation of the c-H-ras gene significantly increases cellular transforming
      activities of Ras. Since posttranslational modification and subsequent membrane
      localization are essential for the biological activities of Ras, we examined
      whether or not the mutation also affects these two factors. The normal (Gly(12))
      or the transforming (Val(12)) c-H-ras gene was expressed in NIH3T3 cells using a
      metallothionein promoter. Expression of either type of Ras was efficiently
      induced by the cadmium treatment of these cells, and immunoprecipitation of
      metabolically labeled cell extracts revealed that both normal and transforming
      Ras were expressed as four differently migrating forms on SDS-polyacrylamide
      gels, two of which were slower migrating cytosolic precursors and the other two
      were faster migrating membrane-bound forms. There was no significant difference
      in half lives between normal and transforming Ras; however, posttranslational
      modification was quite different between the two types of Ras. Transforming Ras
      was processed and became membrane-bound forms much more efficiently than normal
      Ras. Interestingly, posttranslational modification and membrane localization of
      Ras was significantly inhibited when the c-myc oncogene was co-expressed with
      Ras. In contrast to the c-myc oncogene, expression of either wild type or mutant
      p53 did not affect the posttranslational modification of Ras, suggesting that the
      c-myc oncogene specifically impairs the posttranslational modification of Ras.

PMID- 9173083
TI  - Expression of bone matrix proteins during dexamethasone-induced mineralization of
      human bone marrow stromal cells.
AB  - Glucocorticoids have been shown to induce the differentiation of bone marrow
      stromal osteoprogenitor cells into osteoblasts and the mineralization of the
      matrix. Since the expression of bone matrix proteins is closely related to the
      differentiation status of osteoblasts and because matrix proteins may play
      important roles in the mineralization process, we investigated the effects of
      dexamethasone (Dex) on the expression of bone matrix proteins in cultured normal
      human bone marrow stromal cells (HBMSC). Treatment of HBMSC with Dex for 23 days
      resulted in a significant increase in alkaline phosphatase activity with maximum
      values attained on day 20 at which time the cell matrix was mineralized. Northern
      blot analysis revealed an increase in the steady-state mRNA level of alkaline
      phosphatase over 4 weeks of Dex exposure period. The observed increase in the
      alkaline phosphatase mRNA was effective at a Dex concentration as low as 10(-10)
      M with maximum values achieved at 10(-8)M. In contrast, Dex decreased the steady
      state mRNA levels of both bone sialoprotein (BSP) and osteopontin (OPN) over a 4
      week observation period when compared to the corresponding control values. The
      relative BSP and OPN mRNA levels among the Dex treated cultures, however, showed
      a steady increase after more than 1 week exposure. The expression of osteocalcin
      mRNA which was decreased after 1 day Dex exposure was undetectable 4 days later.
      Neither control nor Dex-treated HBMSC secreted osteocalcin into the conditioned
      media in the absence of 1 ,25(OH)(2)D(3) during a 25-day observation period. The
      accumulated data indicate that Dex has profound and varied effects on the
      expression of matrix proteins produced by human bone marrow stromal cells. With
      the induced increment in alkaline phosphatase correlating with the mineralization
      effects of Dex, the observed concomitant decrease in osteopontin and bone
      sialoprotein mRNA levels and the associated decline of osteocalcin are consistent
      with the hypothesis that the regulation of the expression of these highly
      negatively charged proteins is essential in order to maximize the Dex-induced
      mineralization process conditioned by normal human bone marrow stromal
      osteoprogenitor cells.

PMID- 9173084
TI  - Posttranscriptional aspects of the biosynthesis of type 1 collagen pro-alpha
      chains: the effects of posttranslational modifications on synthesis pauses during
      elongation of the pro alpha 1 (I) chain.
AB  - Early studies indicated that chain elongation pauses were prominent during the in
      vivo synthesis of type I procollagen chains, and it was postulated [Kirk et al.,
      (1987): J Biol Chem 262:5540-5545.] that these might have a role in the
      coordination of procollagen I molecular assembly. To examine this postulate,
      polysomes isolated from [(14)C]-Pro-labeled 3T6 cells were subjected to SDS-PAGE.
      The resulting gels were Western blotted and screened with a monoclonal antibody
      (SP1 .D8) directed against the N-terminal region of the pro alpha 1 (I) chain.
      The blots were fluorographed, which also permitted analysis of the pro alpha 2
      (I) chain. There was a prominent pro alpha1 synthesis pause near the completion
      of full-length chain elongation, not matched by a pro alpha 2 pause. The amount
      of labeled polysome-associated near-full length pro alpha 1 (I) chains increased
      in parallel with labeling time. After 24 h in culture -[(14)C-Pro], collagen
      synthesis ceased but unlabeled polysome-associated pro alpha1 chains were readily
      detected by SP1 .D8. Change to fresh culture medium +[(14)C-Pro] reinitiated
      synthesis and permitted tracing of the newly synthesized labeled pro a chains
      through the polysome and intracellular compartments. The secreted procollagen
      molecules had a 2:1 pro alpha 1 (1):pro alpha 2 (I) chain ratio but the polysome
      bound peptides did not. Pulse-chase experiments showed that near-full length pro
      alpha 1 (I) chains remained bound to polysomes as long as 4 h after reinitiation
      of translation but there was no evidence for pro alpha 2 (I) chain accumulation.
      The hydroxylation inhibitor alpha, alpha'-dipyridyl, and triple-helix inhibitors
      cis-hydroxyproline and 3,4 dehydroproline had minimal effects on the buildup of
      polysome-associated pro al chains. The glycosylation inhibitor tunicamycin also
      failed to change the final pro alpha 1 chain pausing, but it did cause the
      appearance of several discrete lower molecular weight pro alpha 1-related
      polypeptides that could not be accounted for simply as the result of lack of N
      linked glycosylation in the C-propeptide regions. Disulfide bond experiments
      showed that some of the paused nascent polysome-associated pro alpha 1 (I) chains
      were disulfide bonded. Thus, while synthesis of pro alpha 1 (I) and pro alpha 2
      (I) chains proceeds in parallel within the same ER compartments, their elongation
      rates are not coordinated. Interactions leading to heterotrimer formation are a
      late event which may affect the rate of release of the completed pro alpha 1 (I)
      chain from the polysome. The release of completed nascent pro alpha 1 (I) chains
      from their polysomal complexes is regulated by a mechanism not operating in the
      synthesis of pro alpha 2 (I) chains. The pro alpha 1 (I) chain release process is
      not connected directly with hydroxylation, glycosylation or triple-helix
      formation.

PMID- 9173085
TI  - Role of Hsp70 synthesis in the fate of the insulin-receptor complex after heat
      shock in cultured fetal hepatocytes.
AB  - The influence of a mild heat shock on the fate of the insulin-receptor complex
      was studied in cultured fetal rat hepatocytes whose insulin glycogenic response
      is sensitive to heat [Zachayus and Plas (1995): J Cell Physiol 162:330-340].
      After exposure from 15 min to 2 hr at 42.5 degrees C, the amount of (125)1
      insulin associated with cells at 37 degrees C was progressively decreased (by 35%
      after 1 hr), while the release of (125)1-insulin degradation products into the
      medium was also inhibited (by 75%), more than expected from the decrease in
      insulin binding. Heat shock did not affect the insulin-induced internalization of
      cell surface insulin receptors but progressively suppressed the recycling at 37
      degrees C of receptors previously internalized at 42.5 degrees C in the presence
      of insulin. When compared to the inhibitory effects of chloroquine on insulin
      degradation and insulin receptor recycling, which were immediate (within 15 min),
      those of heat shock developed within 1 hr of heating. The protein level of
      insulin receptors was not modified after heat shock and during recovery at 37
      degrees C, while that of Hsp72/73 exhibited a transitory accumulation inversely
      correlated with variations in insulin binding, as assayed by Western
      immunoblotting from whole cell extracts. Coimmunoprecipitation experiments
      revealed a heat shock-stimulated association of Hsp72/73 with the insulin
      receptor. Affinity labeling showed an interaction between (125)1-insulin and
      Hsp72/73 in control cells, which was inhibited by heat shock. These results
      suggest that increased Hsp72/73 synthesis interfered with insulin degradation and
      prevented the recycling of the insulin receptor and its further thermal damage
      via a possible chaperone-like action in fetal hepatocytes submitted to heat
      stress.

PMID- 9173086
TI  - TGF-beta receptors are diminished after retinoid exposure in rat liver epithelial
      cells.
AB  - When rat liver epithelial cells were exposed to retinoic acid or retinol for 24
      hr, the levels of transforming growth factor-beta (TGF-beta) receptors were
      reduced in a dose-dependent way. The decrease appeared after 12 hr of incubation
      with the retinoids and binding levels remained low until 24 hr after the removal
      of the molecules. Retinoid treatment induced a fourfold enhancement of
      transglutaminase (TGase) activity in the cell membranes, and cystamine, an
      inhibitor of TGase, prevented the decrease of the receptors. Neutralization of
      TGF-beta by a monoclonal antibody did not suppress the decrease of the binding
      levels, indicating that decreased TGF-beta binding capacity was not due merely to
      the internalization of ligand-bound receptors promoted by a stimulation of TCF
      beta synthesis. Thus, retinoid treatment resulted in an intense disappearance of
      the functional receptors from the membranes that seemed to be mediated by
      increased TGase activity. This phenomenon can represent a strong signal
      attenuation for TGF-beta following retinoid exposure.

PMID- 9173087
TI  - Overexpression of protein kinase FA/GSK-3 alpha (a proline-directed protein
      kinase) correlates with human hepatoma dedifferentiation/progression.
AB  - Computer analysis of protein phosphorylation sites sequence revealed that
      transcriptional factors and viral oncoproteins are prime targets for regulation
      of proline-directed protein phosphorylation, suggesting an association of the
      proline-directed protein kinase (PDPK) family with neoplastic transformation and
      tumorigenesis. In this report, an immunoprecipitate activity assay of protein
      kinase FA/glycogen synthase kinase-3 alpha (kinase F(A)/GSK-3 alpha) (a member of
      PDPK family) has been optimized for human hepatoma and used to demonstrate for
      the first time significantly increased (P < 0.01) activity in poorly
      differentiated SK-Hep-1 hepatoma (24.2 +/- 2.8 units/mg) and moderately
      differentiated Mahlavu hepatoma (14.5 +/- 2.2 units/mg) when compared to well
      differentiated Hep 3B hepatoma (8.0 +/- 2.4 units/mg). Immunoblotting analysis
      revealed that increased activity of kinase FA/GSK-3 alpha is due to
      overexpression of the protein. Elevated kinase FA/GSK-3 alpha expression in human
      hepatoma biopsies relative to normal liver tissue was found to be even more
      profound. This kinase appeared to be fivefold overexpressed in well
      differentiated hepatoma and 13-fold overexpressed in poorly differentiated
      hepatoma when compared to normal liver tissue. Taken together, the results
      provide initial evidence that overexpression of kinase FA/GSK-3 alpha is involved
      in human hepatoma dedifferentiation/progression. Since kinase FA/GSK-3 alpha is a
      PDPK, the results further support a potential role of this kinase in human liver
      tumorigenesis, especially in its dedifferentiation/progression.

PMID- 9173088
TI  - Phenotypic expression of marrow cells when grown on various substrata.
AB  - Our aim was to study the role of various extracellular matrices (ECM) on growth
      and differentiation of marrow stromal cells in vitro. Morphology changes, gene
      expression, and enzymatic activities were monitored in stromal osteoblastic MBA
      15 and adipocytic 14F1.1 cells. These stromal cells were plated on dishes
      precoated with different substrata, such as matrigel (basement membrane),
      collagen type I, and endothelial ECM, and compared with cells plated on protein
      free dishes. Striking morphological differences were observed when the cells grew
      on these different substrata. Changes in cell shape and growth also led to
      differential mRNA expression and enzymatic activities. When MBA-15 cells were
      plated on collagen, there was a decrease in mRNA for alkaline phosphatase (ALK
      P), osteopontin (OP), and osteonectin (ON), and an increase in mRNA for
      procollagen (I). A differential effect was noted on 14F1.1 cells, the mRNA for
      ALK-P increased, the expressions of OP and ON lowered, and no expression for
      procollagen (I) was monitored. MBA-15 cells cultured on matrigel had decreased
      mRNA for ALK-P and OP, while they had increased ON mRNA expression and remained
      unchanged for procollagen I. No change in mRNA expression by 14F1.1 cells was
      monitored when cultured on matrigel. Functional enzymatic activities of ALK-P
      markedly decreased in MBA-15 cells cultured on various substrata, and increased
      or were unchanged in 14F1.1 cells. An additional enzyme, neutral endopeptidase
      (CD10/NEP), altered differentially in both cell types; this enzymatic activity
      increased or was unchanged when cells were cultured on these matrices. The
      results indicate a specific role for different ECM on various stromal cell types
      and their function.

PMID- 9173089
TI  - Modulation of protein phosphorylation and stress protein expression by okadaic
      acid on heat shock cells.
AB  - We have demonstrated that pretreatment but not post-treatment with okadaic acid
      (OA) can aggravate cytotoxicity as well as alter the kinetics of stress protein
      expression and protein phosphorylation in heat shocked cells. Compared to heat
      shock, cells recovering from 1 hr pretreatment of OA at 200 nM and cotreated with
      heat shock at 45 degrees C for the last 15 min of incubation (OA-->HS treatment)
      exhibited enhanced induction of heat shock proteins (HSPs) 70 and 110. In
      addition to enhanced expression, the attenuation of HSC70 and HSP90 after the
      induction peaks was also delayed in OA-->HS-treated cells. The above treatment
      also resulted in the rapid induction of the 78 kDa glucose-regulated protein
      (GRP78), which expression remained constant in cells recovering from treatment
      with 200 nM OA for 1 hr, heat shocked at 45 degrees C for 15 min, or in combined
      treatment in reversed order (HS-->OA treatment). Enhanced phosphorylation of
      vimentin and proteins with molecular weights of 65, 40, and 33 kDa and decreased
      phosphorylation of a protein with a molecular weight of 29 kDa were also observed
      in cells recovering from OA-->HS treatment. Again, protein phosphorylation in
      cells recovering from HS-->OA treatment did not differ from those in cells
      treated only with heat shock. Since the alteration in the kinetics of stress
      protein expression and protein phosphorylation was tightly correlated, we
      concluded that there is a critical link between induction of the stress proteins
      and phosphorylation of specific proteins. Furthermore, the rapid induction of
      GRP78 under the experimental condition offered a novel avenue for studying the
      regulation of its expression.

PMID- 9173090
TI  - Role of alpha v beta 5 and alpha v beta 6 integrin glycosylation in the adhesion
      of a colonic adenocarcinoma cell line (HT29-D4).
AB  - We have previously characterized the expression of the alpha nu beta 5 and alpha
      nu beta 6 integrins as major receptors for the human colonic adenocarcinoma cell
      line (HT29-D4), on vitronectin and fibronectin, respectively [Lehmann et al.
      (1994): Cancer Res 54:2102-2107]. In the present work we investigated the
      glycosylation role of these integrins in their adhesive functions. To this end,
      we used glycohydrolases to show that cell surface integrins were N-glycosylated
      and sialylated, and that only the alpha v subunit carried some immature
      oligosaccharide side chains. To alter the glycosylation state of the cell surface
      alpha v beta 5 and alpha v beta 6 integrins, we used two oligosaccharide
      processing inhibitors: 1-deoxymannojirimycin (dMNJ) and tunicamycin (TM).
      Following treatment of HT29-D4 cells with dMNJ, cell surface alpha v beta 5 and
      alpha v beta 6 carried only high-mannose-type sugar chains, while TM-treated
      cells expressed de-N-glycosylated integrins. Neither alpha/beta heterodimers
      assembly nor cell surface expression were impaired in the presence of the drugs.
      Finally, we established that adhesion of dMNJ- or TM-treated cells was altered on
      both vitronectin and fibronectin substrata, whereas the adhesion of these cells
      on laminin or collagen type I was virtually unchanged.

PMID- 9173091
TI  - Specific involvement of glypican in thrombin adhesive properties.
AB  - We have previously demonstrated that thrombin possesses an active yet cryptic Arg
      Gly-Asp (RGD) site which upon exposure induces endothelial cell (EC) adhesion via
      alpha nu beta 3 integrin [Bar-Shavit et al. (1991): J Cell Biol 112:335]. This
      was achieved in the presence of cell surface-associated heparan sulfate
      proteoglycans (HSPG) and exceedingly low concentrations of plasmin [Bar-Shavit et
      al. (1993): J Cell Biol 123:1279]. A portion of the cell surface-associated HSPG
      (glypican) is anchored via a covalently linked glycosyl-phosphatidylinositol (PI)
      residue, which can be released by treatment with glycosyl-PI-specific
      phospholipase C (PI-PLC). We report here that exposure of either bovine aortic
      EC, smooth muscle cells (SMC), or wild-type CHO cells to PI-PLC released HSPG
      involved in the conversion of thrombin to an adhesive molecule. The adhesion
      promoting activity of the released HSPG was abolished following treatment with
      heparinase but not chondroitinase ABC. Incubation of thrombin with heparan
      sulfate-deficient CHO cells or cells that were pretreated with PI-PLC failed to
      induce its conversion to an adhesive molecule, indicating that glypican was
      playing a major role in this conversion. Moreover, affinity-purified glypican,
      but not syndecan or fibroglycan, elicited efficient conversion of plasmin-treated
      thrombin into an adhesive molecule. Antibodies raised against the RGD site in
      thrombin failed to interact with native thrombin, prothrombin, or the RGD site in
      other adhesive proteins such as vitronectin, fibrinogen, or fibronectin. Anti
      thrombin-RGD antibodies which blocked the adhesion-promoting activity of thrombin
      were also capable of recognizing thrombin that was first incubated with a
      suboptimal concentration of plasm in in the presence of PI-PLC-released HSPG.
      Heparin, heparan sulfate, and PI-PLC-released HSPG had no effect on other
      cellular properties of thrombin such as receptor binding and growth-promoting
      activity. Altogether we have demonstrated that the heparin binding domain in
      thrombin plays a specific role in promoting thrombin adhesive properties and that
      membrane-associated glypican is likely to be the major physiological inducer of
      this property.

PMID- 9173092
TI  - Simultaneous digital imaging analysis of cytosolic calcium and morphological
      change in platelets activated by surface contact.
AB  - The dynamic change of cytoplasmic Ca(2)+ concentration ([Ca(2)+]i) and
      morphological change were investigated simultaneously by confocal laser scanning
      microscopy using fluo-3 and by differential interference contrast optics in
      platelets activated by contact with the following types of surfaces: native glass
      and glass treated with poly-L-lysine (PLL), fibrinogen (Fg), or von Willebrand
      factor (vWF). The initial [Ca(2)+]i values just after the surface contact were
      comparable (approximately 100 nM) among platelets deposited on the four surface
      types. On the PLL-surface, no morphological change or [Ca(2)+]i elevation was
      observed. Glass-, Fg-, and vWF-surface adhered platelets showed pseudopod
      formation and spreading associated with the inhomogeneous [Ca(2)+]i rise. The
      platelets on the Fg-surface were the most active in terms of [Ca(2)+]i rise and
      morphological change. During pseudopod formation, the mean [Ca(2)+]i value was
      maximal and localized high [Ca(2)+]i zones were observed inside pseudopods, as
      well as in the center of the platelets. After spreading, high [Ca(2)+]i zones
      still remained in the center of the cell. This new technique enabled simultaneous
      observation of [Ca(2)+]i and cell shape and we clearly demonstrated a close
      relationship between [Ca(2)+]i and morphological alterations.

PMID- 9173093
TI  - Specific inhibition of c-fos proto-oncogene expression by triple-helix-forming
      oligonucleotides.
AB  - The promoter region of the c-fos oncogene 5' flanking sequence contains enhancer
      elements crucial for binding nuclear factors that regulate transcription
      following cell proliferation and differentiation. Single-stranded
      deoxyoligonucleotides were chosen for modulation of c-fos protooncogene
      expression because of their high-affinity binding to specific nucleotide
      sequences. We designed two oligonucleotides that form a triple-helix complex on
      the retinoblastoma gene product-responsible element of the c-fos oncogene.
      Modification of the DNA triplex with dimethyl sulfate and affinity cleaving
      assays demonstrate that the predicted oligonucleotides form a DNA triplex
      structure with the c-fos promoter in a sequence-specific manner. Tumorigenic and
      non-tumorigenic fibroblasts were transiently transfected with fos-CAT plasmid
      modified with alkylating triplex-forming oligonucleotide reagents. A dramatic
      depression of CAT activity was found when the cross-linked triple helix complex
      at the retinoblastoma gene product-related site of the c-fos promoter was used.
      These experiments suggest that transcription of individual genes can be
      selectively modulated in cell culture by sequence specific triplex formation in
      regulatory enhancer sequences.

PMID- 9173096
TI  - The next 25 years.

PMID- 9173095
TI  - Proceedings of the 28th Bethesda Conference. Practice Guidelines and the Quality
      of Care. Bethesda, Maryland, October 21-22, 1996.

PMID- 9173094
TI  - Bone tissue-specific transcription of the osteocalcin gene: role of an activator
      osteoblast-specific complex and suppressor hox proteins that bind the OC box.
AB  - Bone-specific expression of the osteocalcin gene is transcriptionally controlled.
      Deletion analysis of osteocalcin promoter sequences by transient transfection of
      osseous (ROS 17/2.8) and nonosseous (R2 fibroblast) cells revealed that the most
      proximal 108 nucleotides are sufficient to confer tissue-specific expression. By
      gel mobility shift assays with wild-type and mutated oligonucleotides and nuclear
      extracts from several different cell lines we identified a novel transcription
      factor complex which exhibits sequence-specific interactions with the primary
      transcriptional element, the OC box (nt -99 to -76). This OC box binding protein
      (OCBP) is present only in osteoblast-like cells. Methylation interference
      demonstrated association of the factor with OC box sequences overlapping the Msx
      homeodomain consensus binding site. By assaying several mutations of the OC box,
      both in gel shift and transient transfection studies using ROS 17/2.8, we show
      the following. First, binding of OCBP correlates with osteocalcin promoter
      activity in ROS 17/2.8 cells. Increased binding leads to a 2-3-fold increase in
      transcription, while decreased binding results in transcription 30-40% of
      control. Second, homeodomain protein binding suppresses transcription. However,
      Msx expression is critical for full development of the bone phenotype as
      determined by antisense studies. Last, we show that one of the mutations of the
      OC box permits expression of osteocalcin in non-osseous cell lines. In summary,
      we demonstrate association of at least two classes of tissue-restricted
      transcription factors with the OC box element, the OCBP and Msx proteins,
      supporting the concept that these sequences contribute to defining tissue
      specificity.

PMID- 9173098
TI  - Consent form.

PMID- 9173097
TI  - Mandibular reconstruction by secondary reimplantation of resected segments: a
      preliminary report.

PMID- 9173099
TI  - Laceration repair with tissue adhesive in children.

PMID- 9173100
TI  - Dependence of divalent metal ions on phosphotransferase activity of osseous plate
      alkaline phosphatase.
AB  - Kinetic evidence for the role of divalent metal ions in the phosphotransferase
      activity of polidocanol-solubilized alkaline phosphatase from osseous plate is
      reported. Ethylenediamine tetreacetate, 1,10-phenanthrolin, and Chelex-100 were
      used to prepare metal-depleted alkaline phosphatase. Except for Chelex-100,
      either irreversible inactivation of the enzyme or incomplete removal of metal
      ions occurred. After Chelex-100 treatment, full hydrolase activity of alkaline
      phosphatase was recovered upon addition of metal ions. On the other hand, only
      20% of transferase activity was restored with 0.1 microM ZnCl2, in the presence
      of 1.0 M diethanolamine as phosphate acceptor. In the presence of 0.1 mM MgCl2,
      the recovery of transferase activity increased to 63%. Independently of the
      phosphate acceptor used, the transferase activity of the metal-depleted alkaline
      phosphatase was fully restored by 8 microM ZnCl2 plus 5 mM MgCl2. In the presence
      of diethanolamine as phosphate acceptor, manganese, cobalt, and calcium ions did
      not stimulate the transferase activity. However, manganese and cobalt-enzyme
      catalyzed the transfer of phosphate to glycerol and glucose.

PMID- 9173102
TI  - Crisis management training helps young anesthesiologist successfully manage mid
      air passenger cardiac arrest.

PMID- 9173101
TI  - How amino acids control the binding of Cu(II) ions to DNA (II): effect of basic
      amino acid residues and the chirality on the orientation of the complexes.
AB  - The binding structures of bis-lysine and bis-arginine complexes of copper(II) on
      highly oriented DNA fibers have been investigated by ESR spectroscopy. These
      complexes bind to DNA in two different modes; species A in one mode has a planar
      coordination structure as in solution, and species B in the other mode has a
      distorted planar structure on the DNA. The relative amount of A and B changes
      with the conformation of the DNA, as well as with the type and chirality of the
      amino acids. Arginine forms A more than lysine. On A-form DNA fibers, A for L
      lysine and L-arginine complexes are bound with the angle theta = 45 degrees
      between the g// axis and the DNA helical axis, while A and B for the D-isomers
      are almost randomly oriented. L-arginine fixes the orientation of A on A-form DNA
      fibers more firmly than L-lysine. On B-form DNA fibers, the orientation of the
      complexes is modulated dynamically, and the g// axes have a tendency to be
      reoriented along the fiber axis by the conformational change of the DNA from A-
      to B-form at room temperature. The D-arginine complex on B-form DNA is peculiar
      in that it rotates ore freely than the other complexes at room temperature and
      shows only the A at low temperature.

PMID- 9173103
TI  - [Imaging diagnosis--3-dimensional helical imaging. Pharyngeal cancer].

PMID- 9173104
TI  - Multidex Gel for use in wound care.

PMID- 9173105
TI  - Neuronal intestinal dysplasia in an adult.

PMID- 9173106
TI  - Prognostic genotyping and matching in renal transplantation.

PMID- 9173107
TI  - Dialysis for surgical acute renal failure.

PMID- 9173108
TI  - The role of the transplant coordinator.

PMID- 9173109
TI  - Techniques and results of renal transplantation.

PMID- 9173110
TI  - Some recent ethical issues in transplantation.

PMID- 9173111
TI  - Vascular access for haemodialysis.

PMID- 9173112
TI  - Urological complications after renal transplantation.

PMID- 9173113
TI  - Donor management, multi organ procurement and renal preservation.

PMID- 9173114
TI  - The radiologist's contribution to the diagnosis and treatment of renal transplant
      disorders.

PMID- 9173115
TI  - [Kidney cancer: the basic symptoms taking into account the histological form].
AB  - Retrospective case records analysis of 126 patients operated on in urologic
      department for the kidney cancer during 1970-1991 yrs period of time. The
      severity of such symptoms as hematuria, pain and palpable tumor in accordance
      with various morphological types of the disease was studied up. The data obtained
      witnesses the presence of close correlational relation between morphological form
      of kidney cancer and clinical features of the disease, and that's why they can be
      used as the diagnostic and practical guides.

PMID- 9173117
TI  - [The efficacy of palliative operations in tumors of the 3rd cerebral ventricle].
AB  - Results of treatment of 79 patients with III brain ventricle tumor, whom
      palliative liquoroshunting operations were conducted, were analysed. In the
      presence of significant liquorodynamic disturbances all the operations has been
      trusted their efficacy, and this permitted to prolong the life span of the
      patients. Liquoroshunting operations can be used as the first stage of treatment
      in the patients with hypertensive-hydrocephalic syndrome for the general
      condition stabilization before tumor excision performance.

PMID- 9173116
TI  - [The principles and late results of the surgical treatment of chronic subdural
      hematoma in nursing infants].
AB  - Principles of surgical treatment of 68 infants with chronic subdural hematoma are
      substantiated. Late follow-up results analysis has shown that the application of
      all of the modern neurosurgical diagnostic methods permits to choose correctly
      the method of treatment and to prognosticate its result. Result of treatment was
      not influenced substantially by the hematoma evacuation procedure performance, in
      37 patients good result occurred. Poor result of patient's treatment is due to
      the concomitant or caused by hematoma brain affection.

PMID- 9173118
TI  - [The role of dysembryogenesis in the development of spinal cord tumors].
AB  - Experience of treatment of 36 patients with extramedullary spinal cord tumors is
      summarized. Pigmented macules, papillomas or the spinous processes painfulness
      while irritation were determined on skin in accordance to tumor localization in
      the innervation zone of one or two segments.

PMID- 9173119
TI  - [The morphological characteristics of craniocerebral and cerebrospinal hernias in
      children after the accident at the Chernobyl Atomic Electric Power Station].
AB  - In the post-Chernobyl period of time the quantity of children operated for
      congenital cerebral and cerebrospinal hernia has been increased almost by two
      times. The signs of degeneration were not observed while morphological study of
      hernial sac wall in 96 children operated on from 1981 till 1986 year. Of 167
      children operated on after the Chernobyl accident (1986-1992 yrs) in 10 (5.9%) of
      them the degeneration of substantia medullaris astrocytes was observed.

PMID- 9173120
TI  - [The initial experience of using fraxiparin in extracorporeal detoxication in
      clinical cardiology].
AB  - Procedures, connected with extracorporal blood circulation--hemodialysis,
      hemosorption and plasmapheresis--were used in complex of treatment in 30 patients
      with various cardiovascular diseases. As an anticoagulant in 8 patients was used
      the preparation of low molecular heparine (Fraxiparine) produced by "Sanofi"
      (France) firm, and in 22-heparin, produced by "Polfa" (Poland). Ascertained
      advantages of Fraxiparine versus heparin were: possibility of single injection of
      preparation, the reducing of total dose magnitude, which is needed for one
      curative act conduction, lowering by 70% approximately the hemorrhagic
      complications rate.

PMID- 9173121
TI  - [The immunomorphological changes in the duodenal mucosa in peptic ulcer].
AB  - Results of immunomorphological investigation of the duodenal tissue, taken for
      biopsy at the time of operative intervention for the duodenal ulcer in 23
      patients, are presented. Lowering of IgA-synthesizing cells count in lamina
      propria of the duodenal mucosa was determined. Deposition of IgG and the C3
      component in vessels, the enlargement of IgA-synthesizing cells confirms the
      presence of antigenic properties of affected duodenum and the participation of
      immunocomplex and autoimmune mechanisms in pathogenesis of the duodenal ulcer
      disease.

PMID- 9173122
TI  - [Means to improve the results of the treatment of organic diseases of the
      hepatopancreatoduodenal area in patients with obstructive jaundice].
AB  - Among 116 patients with diseases of hepatopancreatoduodenal zone organs,
      complicated with obstructive jaundice, the group of heightened operational risk
      was picked out. As the first stage of surgical treatment the laparoscopy was
      applied with subsequent operative intervention conduction using laparotomy. In
      critically ill patients the endoscopic intervention was the last stage of
      surgical treatment. In the group of heightened operative risk lethality was 3.9%.

PMID- 9173123
TI  - [The pathogenesis, classification and treatment of acute and recurrent traumatic
      stricture of the urethra].
AB  - The influence of uresis disorders, injuries of pelvic neural plexuses, anatomic
      pathways between urethra and spermiducts on the disease course and prognosis was
      studied in 128 patients with complicated and recurrent urethral stricture. Data
      concerning mechanism of pathologic process spread are adduced, classification of
      complicated and recurrent traumatic urethral stricture is proposed. Indications
      for urethral stricture resection with prostatectomy and prostatovesiculectomy,
      anastomosis between urethra and neck of the urinary bladder for urea passage
      disorders by upper and lower urinary tracts.

PMID- 9173124
TI  - [Pulmonary alveolar microlithiasis].
AB  - The literary data and own observation of pulmonary microlithiasis, an extremely
      rare disease, are presented. The results of investigation of local immunity in
      patients were depicted.

PMID- 9173125
TI  - [Stages in the transition of acute pleurisy into chronic].
AB  - Literary data concerning chronic pleuritis incidence, pathomorphological and
      pathophysiological aspects of the disease chronization, leading to the chronic
      pulmonary heart development, are adduced. Pleurectomy is the prophylactic method
      of this complication beginning, i.e. is the invalidization prophylaxis method.
      Clinico-roentgenological classification is proposed, which permits to determine
      the conservative treatment duration and indications for the operation conduction.

PMID- 9173126
TI  - [The complex grafting of the internal thoracic artery to the coronary arteries].
AB  - Among the 34 complex internal thoracic artery (ITA) to coronary artery grafts,
      there were bilateral (in 20 patients), bifurcated (in 8), sequential (in 4),
      "free" (in 1), left ITA and right radial artery (in 1). It was performed with the
      "no-touch" technique to the ascending and transverse aorta, cardiopulmonary
      bypass with an arterial inflow cannulation to the left common femoral artery,
      with a beating, warm, and vented heart and severe bradycardia induced by a short
      acting beta 1-blocker. Two latter factors were used to decrease myocardial oxygen
      consumption and facilitate construction of the ITA to coronary artery
      anastomoses. There were no operative mortality.

PMID- 9173127
TI  - [Complex cases in heart surgery].
AB  - Between January 1968 and December 1993, 837 patients underwent cardiac operations
      with were either complex or performed in the presence of a life threatening
      disease of other vital organs. Of them 74 (8.8%) patients have died within 30
      days after the operation. A substantial number of the operations and associated
      operative death included left ventricular (LV) aneurysmectomy or plication or LV
      endoaneurysmectomy with coronary artery bypass (CAB) grafts with or without other
      cardiac procedures, cardiac reoperations, CAB grafts and mitral or aortic valve
      replacement, combined mitral and aortic valve replacement (MAVR) with or without
      tricuspid valve replacement and CAB grafts, CAB grafting for an end-stage
      coronary artery disease (CAD), emergency CAB grafts for an acute myocardial
      infarction with cardiogenic shock, complex internal thoracic artery (ITA)
      grafting, and miscellaneous. The best results were achieved in CAB grafts for an
      end-stage CAD, complex ITA grafting, CAB grafts with mitral or aortic valve
      replacement, cardiac reoperations. MAVR and miscellaneous. This is probably,
      related to an intensive treatment of congestive heart failure (CHF) before the
      operation, pretreatment with the oxygen free radical inhibitor (allopurinol),
      selective use of an intraaortic balloon assist device and LV venting, routine use
      of hemoconcentrator (ultrafiltration) during cardiopulmonary bypass in those with
      CHF, thorough myocardial protection and a complete coronary revascularization.

PMID- 9173128
TI  - [The use of low heparin doses for the prevention of postoperative thrombosis of
      the deep veins and of pulmonary artery thromboembolism].
AB  - The results of small doses heparin application (15,000 units) for the prophylaxis
      of postoperative deep vein thrombosis and the pulmonary artery thromboembolism
      were analyzed. The lowering of incidence of deep vein thrombosis from 32 to 8%
      was determined using 125I-fibrinogen. Of 3540 patients aged 40 years old and
      more, while the operation duration no less than 1 hour and anticoagulant
      administered, 6 (0.16%) died due to the pulmonary artery thromboembolism. The
      mortality was 9 times more in the group of patients, whom the prophylaxis was not
      conducted. Severe hemorrhagic complications after heparin application in above
      mentioned dose were not noted.

PMID- 9173129
TI  - [The efferent therapy of Raynaud's phenomenon].
AB  - The method of discrete plasmacytapheresis was applied for the treatment of 8
      patients with primary and 18 with secondary Raynaud's phenomenon. The
      incorporation of this method in the therapeutic complex have promoted the
      achievement of clinical improvement in the whole of the patients with primary and
      in 13 with secondary Raynaud's phenomenon. Remission lasted from 1.5 months till
      4.5 years. Positive effect is caused by the improvement of blood rheological
      properties on the hemodilution background, the excretion of pathological
      substances from blood flow.

PMID- 9173130
TI  - [The function of the musculo-venous "pump" of the foot in varicose veins].
AB  - The functional state of foot musculo-venous "pump" was studied with the help of
      distal and retrograde phlebography. rheovasography and phlebotonometry in 148
      patients with varicose disease. The authors suggested that in the base of its
      dysfunction lies the foot deep vein ectasis and the varicose insufficiency of
      communicating veins connected with them.

PMID- 9173131
TI  - [A rare case of uterine fibromyoma simulating acute intestinal obstruction and
      causing acute urinary retention].

PMID- 9173132
TI  - [Extensive pulmonectomy with resection of an atrium].

PMID- 9173133
TI  - [Cases of heart wounds in children].

PMID- 9173134
TI  - [The incompetence of heart wound sutures].

PMID- 9173135
TI  - [The treatment of bursitis of the olecranon at a polyclinic].

PMID- 9173136
TI  - [Omentoplasty in a patient with osteomyelitis of the ribs and sternum].

PMID- 9173137
TI  - [The treatment of patients with pseudarthrosis and a defect of the long bones].

PMID- 9173138
TI  - [The 1st (XVII) Congress of Surgeons of Ukraine].

PMID- 9173139
TI  - [The one-stage surgical treatment of hypospadias in children].
AB  - Principles and results of one-stage plastic operation, conducted in 49 children
      with hypospadias, are depicted. MAGPI procedure was applied in 11 patients with
      hypospadias of glans penis. There were no complications. Mustarde procedure was
      applied in 28 patients with penile hypospadias. Urinary fistula occurred in 3
      patients, of them in 2 cases has been closed spontaneously and in 1--surgically
      excised. Broadbent operation was performed in 10 patients for penile-scrotal
      hypospadias. In 4 of them urinary fistula occurred. In all the patients good
      anatomic-functional result has been achieved, Performance of the procedure on
      tissues with rich blood supply is an advantage of one-stage operation applied for
      hypospadias treatment.

PMID- 9173140
TI  - [The use of the laser in the surgical treatment of acute intestinal obstruction
      and the prevention of adhesive disease].

PMID- 9173141
TI  - [The scientific legacy of Prof. G. A. Orlov (1910-1986)].

PMID- 9173142
TI  - [The combined treatment of locally disseminated stomach cancer with intra
      arterial regional chemotherapy].
AB  - The method of a long-term celiac artery catheterization through the lumbar
      transaortic access is proposed. In 56 patients with a 3d stage gastric cancer
      regional intraarterial chemotherapy with 5-fluorouracil was used pre- and
      postoperatively. There was a decrease of postoperative complications from 47.8 +
      6% in surgical treatment to 16.0 +/- 4% in combined treatment. Metastases and
      recurrence were observed in 11 (21.2 + 5%) patients with regional chemotherapy
      and in 34 (58.6 + 6%) patients with surgical treatment only.

PMID- 9173143
TI  - [Therapeutic interventions under ultrasonic control in diseases of the abdominal
      cavity organs].
AB  - The results of 212 transcutaneous therapeutical abdominal interventions,
      performed under the ultrasound control, have been analysed. 190 patients have
      been treated. The sectorial ultrasound probe was acting at the frequency of 3
      MHz. The electronic matrix guided the needle. One-stage percutaneous drainage
      with an "umbrella" stylet catheter was used in all cases. Percutaneous drainage
      of the gallbladder was performed in 140 patients; 111 of them had acute
      cholecystitis with a high surgical risk. The operation of cholecystectomy has
      been performed in 32 patients after control of the acute stage of the disease. In
      47 patients percutaneous drainage was indicated in case of liver cysts and
      abscesses, intraliver hematomas, liver pseudocysts, liver pseudoabscesses,
      abdominal abscesses. These types of curative procedures have limited
      contraindications, can be performed irrespective of the patient's condition, and
      in certain cases may be an alternative to major surgical interventions.

PMID- 9173144
TI  - [The restoration of the continuity of the intestinal tube after the Hartmann
      operation].
AB  - The results of reconstructive surgery after the Hartmann [correction of Gartman]
      operation in 67 patients have been analysed. The proper timing of surgery is
      advocated, various types of restoration of uninterrupted intestinal tube are
      described: manual anastomosis, use of a special device, Duhamel type of
      operation, bringing down of the colon. The frequency of anastomotic incompetence
      is 10%, postoperative mortality--4.5%.

PMID- 9173145
TI  - [Assessing the effect of prosthesis of the brachiocephalic trunk].
AB  - The early and long-term results of truncus brachiocephalicus prosthetics in its
      atherosclerotic occlusions are analysed. EEG mapping, radioisotopic examination
      of cerebral circulation before and after surgery, clinical examination were
      performed for evaluation of effectiveness and safety of surgery. The rate of
      mortality was 6.6%. The technical recommendations are provided. All the patients,
      who were discharged after surgery, are alive for 2.6 +/- 0.3 years. No cases of
      recurrence of cerebral circulation disorders were observed. In 100% cases the
      grafts were patent.

PMID- 9173146
TI  - [The treatment of obliterating arterial diseases of the extremities by a
      revascularizing osteotrepanation method].
AB  - A new method to treat obliterative atherosclerosis and thromboangiitis is
      proposed. The method consists in local osteal trepanation of the ischemic
      extremity. The access to the bones was preferably performed in bioactive points.
      The operation called osteotrepanation was performed in 307 patients. 219 of them
      had obliterative atherosclerosis, 75--thromboangiitis obliterans, 13--Raynaud's
      disease. In 63% of patients there was 3d and 4th stage of extremity ischemia. In
      90.5% of patients improvement was observed. After 1 year the improvement of blood
      circulation in the extremity was observed in 92.8% of patients, after 5 years--in
      92,8% also. Revascularizing osteal trepanation is a method of choice in
      thromboangiitis obliterans and in impossibility to perform reconstructive surgery
      in case of grafts thrombosis.

PMID- 9173147
TI  - [The organization of microsurgery at a provincial center].
AB  - The 5-year experience of microsurgery in regional medical centre is analysed.
      1014 operations were performed. Certain managerial items and practical
      recommendations, necessary for development of microsurgery in regional medical
      centers are discussed. The importance of a close contract with other surgical
      services is advocated.

PMID- 9173148
TI  - [The determination of the level of resection of the esophagus taking into account
      its blood supply].
AB  - Inadequate blood supply is one of the major reasons of esophageal anastomosis
      incompetence. The authors have examined esophageal blood supply as regards of the
      operative technique. The esophageal vascular system was studied by the method of
      intraarterial impregnation in 40 cadavers. Two segments, crucial for esophageal
      anastomosis, have been determined: retropericardial segment in case of the lower
      esophageal artery ligation and the upper segment of the thoracic esophagus in
      case of its extreme mobilization in proximal direction and ligation of lower
      thyroid arteries. The results of 175 operations were analysed. The direct
      correlation between the frequency of anastomotic incompetence and the level of
      its formation was determined. In the zone with an inadequate blood supply the
      complication occurred in 4 patients of 25 (16%). In other cases the rate of
      incompetence was 3.2%. No cases of incompetence were observed in 61 patients
      after anastomosis was performed with due regard for esophageal blood supply.

PMID- 9173150
TI  - [The treatment procedure for patients with postoperative hernias taking into
      account the risk index].
AB  - The mathematically determined risk index was used for prognosis of surgery in 122
      patients with postoperative hernias. Standard preoperative treatment and special
      pneumocompression were used to prepare the patients for surgery. High-risk
      patients with the big size hernias should be prepared for surgery for a long
      time. Graded pneumocompression and abdominal wall plastics without decrease of
      the volume of abdominal cavity are advocated in such cases. This approach made it
      possible to decrease the number of early postoperative complications.

PMID- 9173149
TI  - [The surgical treatment of multiple myomas of the left heart].
AB  - 5 patients with multiple left heart myxomas have been followed for 30 years.
      There were 4 females and 1 male at the age of 20-50 years. Two-dimensional
      echocardiography was used for the proper diagnosis in all cases. Open-heart
      surgery is the only possible method of treatment in such a situation. All the
      patients have been successfully operated on. To prevent the recurrence the
      resection of myxomas with a part of interatrial septum and endocardium was
      performed. The trans-sternal approach is the optimal one for the surgery of
      myxomas.

PMID- 9173151
TI  - [A modified suture in the surgical treatment of middle ventral hernias].
AB  - Mechanical stability of the front abdominal wall median anatomic structure
      tissues has been examined in 49 experiments on cadavers. It was found that
      aponeurotic tissue of the edges of sheaths of the rectus abdominis is the most
      firm one. The article analyses different types of sutures used in hernioplasty.
      The authors propose original method of hernioplasty using the most stable
      anatomic structure, formation of narrow tissue duplication with a minimal amount
      of suture material. This method has been used in surgical treatment of 58
      patients with umbilical, postoperative and linea alba hernias. There were no
      recurrences for 3 years.

PMID- 9173152
TI  - [Resolved and unresolved problems of liver surgery].
AB  - Present-day status liver surgery is reviewed. The unsolved problems in surgical
      treatment of patients with focal lesions of the liver are listed. There is a
      deficit of modern diagnostical equipment, especially in rural regions of the
      country. There is a need for special training of specialists for liver surgery
      and a network of the regional centers for liver and biliary surgery, wider
      indications for liver resection.

PMID- 9173153
TI  - [The postcholecystectomy syndrome and its prevention].
AB  - 61 patients had a surgery because of postcholecystectomy syndrome (PCS). In 29
      patients PCS was caused by bile tract diseases, in 15 patients--liver and
      pancreas diseases, in 12 cases disease of other organs. There was no mortality in
      restorative operations. The mortality rate in reconstructive operations was 5%.
      The full clinical and instrumental examination of extrahepatic bile ducts is the
      best way to prevent PCS. PCS was most frequently observed in patients, operated
      on urgently. The results of 79 cases of reconstructive and restorative operations
      in patients operated on urgently are analysed.

PMID- 9173154
TI  - [Endoscopic treatment methods in patients with the postcholecystectomy syndrome].
AB  - 458 patients with postcholecystectomy syndrome have been examined. In 289 (63.1%)
      of them the reason of complication and location of the lesion in biliopancreatic
      duodenal zone have been specified. In 212 (73.4%) patients the endoscopic
      treatment was used, including papillosphincterotomy with removal of concrements;
      suprapapillary choledochoduodenostomy; nasobiliary draining, endoprosthesis. In
      181 (85.4%) of cases these methods appeared to be efficient and final; in 31
      (14.6%) they promoted stabilization of clinical status of patients and performing
      surgery in more favorable conditions. Complications have been registered in 4
      (1.9%) patients, 1 patient (0,47%) died. The authors advocate endoscopic methods
      as methods of choice in postcholecystectomy syndrome.

PMID- 9173155
TI  - [The ultrasonic diagnosis of acute enzymatic cholecystitis].
AB  - Acute enzymatic cholecystitis is a rare form of an acute enzymatic-inflammatory
      process of the gallbladder. In 782 patients with ultrasound signs of
      cholecystitis, acute enzymatic cholecystitis has been found in 10 cases (1.2%).
      The authors describe the most common ultrasound signs of acute enzymatic
      cholecystitis and its morphologic interpretation. The data given in the article
      help early diagnosis of acute enzymatic cholecystitis and to start the treatment
      in time.

PMID- 9173156
TI  - [Retroperitoneosotomy in the surgery of pancreonecrosis].
AB  - Extraperitoneal, transperitoneal and combined peritoneostomy was used in 29
      patients with acute pancreonecrosis and predominant damage of retroperitoneal
      fat. The choice of surgical method depended of the volume of damage of pancreas
      and retroperitoneal fat. The wide opening of necrotized zones of retroperitoneal
      fat, removal of necrotized tissues and adequate drainage can stop further
      spreading of suppuration of the retroperitoneal fat. The mortality rate was 6/29
      (20.7%).

PMID- 9173157
TI  - [Artificially induced suppurative diseases].
AB  - 128 cases of artificially caused purulent diseases have been analysed. All the
      cases were masked as chronic septicemia, recurrent abscesses, nonhealing wounds
      and fever of the unclear origin. The specific features of artificial diseases
      have been pointed out: social status, occupation, provoking factors, specific
      clinical signs--multiple hospitalizations, dominating location of postoperative
      scars and abscesses. Diagnostic principles, including psychological ang
      psychiatric testing are discussed. The neuro-psychiatric disorders were detected
      in most cases. Prevention of such diseases is analysed.

PMID- 9173158
TI  - [The treatment of epithelial coccygeal cyst].
AB  - The dissection of coccygeal duct and closing the wound with a through perforated
      bathing drainage under modified epidural-sacral anaesthesia has been clinically
      approved. The operation was performed 3-4 days after two-step opening and
      cleaning of the abscess. The epithelial duct that doesn't have abscess symptoms
      should be dissected in one step operation. 68 patients underwent one-step surgery
      and in 125 cases two-step surgery has been done. The average time of staying in
      hospital was 15.3 days and 19.1 days, respectively. The double-step surgery of
      epithelial coccygeal duct decreases the level of postoperative septic
      complications and improves the functional and cosmetic results of the treatment.

PMID- 9173159
TI  - [Changes in myocardial hemodynamics and contractile function in patients under
      surgical treatment for prostatic adenoma].
AB  - Hemodynamics and left ventricular myocardial contractility in 170 patients who
      underwent surgery of prostatic adenoma were examined in preoperative period and
      16 days after single-stage transvesical adenomectomy. The age of the patients
      varied from 52 to 85 years. Echocardiography and the dilution method were used
      for the evaluation. The increase of end-diastolic and end-systolic volumes,
      stroke volume, cardiac index, was registered. The combined pharmacological
      treatment made it possible to decrease the number of operative and postoperative
      cardiovascular complications.

PMID- 9173160
TI  - [Clofelin in the anesthesiological support system for surgical operations].
AB  - The article presents clinical experience of using Clofelin in 251 patients as a
      part of general anaesthesia, in postoperative period and in patients with
      peripheral vascular disease. The experiments on 14 rabbits chinchilla have been
      done prior to peridural use of Clofelin. The control for adequate use included
      estimation of hemodynamics parameters, cortizol, vasopressin and B-endorphin
      levels in plasma on different anaesthesia. The analgetic activity of Clofelin in
      postoperative period in patients with peripheral vascular disease was estimated
      by subjective tests using 5 steps of pain estimation scale. The clinical trial
      demonstrated the efficacy of intravenous and peridural use of Clofelin during
      surgery and in postoperative period.

PMID- 9173161
TI  - [Complications of transcutaneous transhepatic endovascular interventions in
      patients with portal hypertension].
AB  - Results of endovasal treatment of 196 patients with portal hypertension and its
      complications are analysed. The total rate of complications is 23.4%, the most
      serious of them were intraabdominal bleeding (2.5%), portal vein thrombosis
      (2.1%). The rate of mortality, related to the complications of transhepatic
      procedures, was 2.5%. The majority of the complications were specific to the
      character of the disease: liver cirrhosis, ascites, high portal pressure,
      coagulating system disorders.

PMID- 9173162
TI  - [The surgical treatment of closed osteomyelitic cavities by using a free full
      thickness skin autograft].
AB  - The article describes a method for treatment of osteomyelitic bone cavities with
      predominant location in the distal part of the tibia and foot bones which are
      under unfavorable muscular protection. It comprises one-stage sequestrectomy and
      plastic correction for repair of the cleansed bone cavity with a free full
      thickness autodermal graft and application of a complete suture to the skin wound
      over the cavity. A principally new feature of the method is application of the
      graft to freshly-treated walls of the bone cavity. A favorable local effect of
      the autodermal graft on the bone cavity is noted: hemostatic, substitutional, and
      reparative. The method was used with a favorable outcome in operations on 10
      patients of 21 to 70 years of age. The osteomyelitic focus was located in the
      femur (2 cases), tibia (6) and calcaneus (2).

PMID- 9173163
TI  - [Posteromediastinal esophagogastroplasty in esophageal surgery].
AB  - The results of esophagogastroplasty in 101 patients are analysed. 41 patients had
      benign esophageal structure, 60 patients--benign esophageal tumors. Certain
      improvements of abdomino-cervical access and closed one-stage
      esophagogastroplasty have been proposed. The improvements include: use of the
      fibro-optical systems for esophageal mobilisation under the visual control,
      bringing down of duodenojejunal transition for prevention of esophageal reflux,
      posterior mediastinum tamponade with a muscle for prevention of mediastinitis,
      aseptic invaginational esophagogastric anastomosis. A significant reduction in
      the rate of purulent complications was observed. The rate of mortality was 7.9%
      (8/101).

PMID- 9173164
TI  - [Transcutaneous ligation of the great saphenous vein in the combined surgical
      treatment of varicose veins of the lower extremities].
AB  - A new method of low extremities varicoses treatment is proposed. The plural
      transcutaneous ligation of venous ramifications is performed before vena saphena
      magna and parva extraction and radial subcutaneous venous ramifications crossing
      are done to prevent intraoperative and postoperative complications, improvement
      of cosmetic effect. The ligatures are removed the 2d postoperative day. The new
      method was used in 67 patients with various forms of varicose disease. Good long
      term (5 years follow-up) results have been achieved.

PMID- 9173165
TI  - [Surgical risk factors: cardiovascular diseases].

PMID- 9173166
TI  - [The surgical treatment of esophageal cancer abroad].

PMID- 9173167
TI  - [Mortality in acute appendicitis--an analysis of a ten-year period].
AB  - This is a retrospective study covering 11,142 acute appendicitis patients,
      operated in the emergency surgery section of the Emergency Medicine Institute
      "Pirogov" over the period 1986 through 1995. Overall mortality amounts to 0.29
      per cent (32 deceased). The dynamic patterns of mortality undergo regression
      analysis. The basic factors having an impact on thanatogenesis are
      comprehensively discussed, namely advanced age, premorbidity background, form of
      appendicitis and postoperative complications. Late diagnosis is the most
      important factor leading to peritonitis development. Also, peritonitis against
      the background of concomitant diseases and advanced age proves to be the
      underlying cause of the fatal outcome of patients--in 24 (75 per cent) of the
      total number of deaths. The necessary measures contributing to make prompt
      diagnosis in acute appendicitis, and undertaking more effective treatment of
      appendicular peritonitis and postoperative complications are outlined.

PMID- 9173168
TI  - [Transendoscopic drug denervation of the stomach in emergency surgical diseases
      of the gastrointestinal tract (a preliminary report)].
AB  - This is the first, preliminary report on the implementation of transendoscopic
      medicamentous denervation of the stomach as a therapeutic approach to acute
      surgical diseases of the gastrointestinal tract. Diminishing the vagus nerve
      influence after the method described contributes to a substantial improvement of
      the treatment results in acute pancreatitis patients by shortening the term of
      therapeutic fasting, avoiding nasogastric tube insertion, and making unnecessary
      H2-blockers application. TEMDS is indicated in all instances of acute
      pancreatitis, bleeding duodenal ulcer, bleeding ulcus pepticum jejuni following
      BII resection of the stomach.

PMID- 9173169
TI  - [Anaerobic surgical infection and septic shock].
AB  - In the period 1990 through 1995, one-hundred patients operated for acute abdomen
      or admitted on a routine basis, presenting evidence of anaerobic infection,
      undergo treatment in the clinic of emergency surgery. Septic shock develops in
      10/100 patients (10 per cent). In six of the latter the outcome is fatal--three
      with infection caused by spore-forming anaerobes (gas gangrene of the inguinal
      region--of Fournier, and anterior abdominal wall--anus praeternaturalis--two),
      and three with infection caused by non-spore-forming anaerobes (mixed anaerobic
      aerobic infection). Anaerobic surgical infection and septic shock specificity is
      discussed, with an algorithm of therapeutic approach, based on clinical
      experience had with 100 patients, being proposed in either of them. Special
      emphasis is laid on antibiotic prophylaxis against anaerobic surgical infection.
      Its implementation in the concrete clinical conditions in this country demands a
      clearcut hospital drug policy (adoption of the "Drug Formularies" system), and
      elaboration of a new economical approach to the choice of antibacterial agents
      (using some of the forms of pharmaco-economical analysis, practicable with a view
      to the Bulgarian health-care model).

PMID- 9173170
TI  - [Percutaneous transthoracic drainage in pleural collections--the pros and cons
      from the surgical viewpoint].
AB  - An attempt is made at specifying the indications for inserting percutaneous
      transthoracic drain after Seldinger's method. The clinical case material analyzed
      for the purpose covers 761 patients over a three-year period (1993 through 1995),
      with 329 of them drained for pneumothorax, 266--hemothorax, and 66-
      hemopneumothorax. In 54 cases (7.1 percent) switching to surgical draining is
      necessitated, in 41 (5.39 percent) correction of the drain is done because of
      inefficiency, and in 96 (12.61 percent)--patency checking and its restoration on
      the serioscope table. A classification of pathological pleural collections is
      suggested which proves helpful in estimating whether or not a tube thoracic or
      percutaneous drain should be employed. The surgeon is cautioned that his
      assessment should be by no means influenced by the easier procedure under the
      excuse that it is the method of choice for the patient. Last but not least, one
      should give due consideration to the financial aspects: percutaneous drainage of
      the pleural cavity costs about 80 DM, whereas a cigarette thoracic drain costs
      about 100 leva at the time of analyzing the material.

PMID- 9173171
TI  - [Thymectomy in myasthenia gravis---experience with 173 surgical patients].
AB  - Over a 13-year period, 173 patients with myasthenia gravis--69 per cent men and
      31 per cent women--undergo operative treatment in the clinic of thoracic surgery
      with oncology at the Military Medical Academy--Sofia. Most patients present
      generalized form of the disease. The operation consists in longitudinal
      sternotomy. In the last few years, a new approach to preoperative preparation and
      postoperative treatment of the patients is used. As the result of strict long
      term postoperative monitoring, plasmapheresis application, immunomodulation and
      adequate intensive care, the rate of complications is greatly reduced with not a
      single fatal outcome being recorded.

PMID- 9173173
TI  - [Current anesthesia problems in minor proctological operations].
AB  - Surgical interventions, performed routinely or on an emergency basis in the
      clinic of abdominal surgery are mostly proctologic. All patients operated in the
      clinic are analyzed with a special reference to the modern methods of analgesia
      used.

PMID- 9173172
TI  - [The results after an organ-preserving operation and total thyroidectomy in
      differentiated thyroid carcinoma].
AB  - A total of 196 patients with differentiated thyroid gland carcinoma are operated
      over the period 1980 through 1994, and followed up over periods ranging from 1 to
      14 years after the operation. Surgical treatment consists in total thyroidectomy
      in 39.8 per cent of the cases, and organ salvaging operation--in 60.2 per cent.
      In 124 instances the histological diagnosis is papillary carcinoma, and in 72-
      follicular carcinoma. Local relapses and lethality are higher in patients with
      total thyroidectomy--6.4 per cent local recurrences and 3.8 per cent lethality,
      whereas in the group of organ-salvaging operations--1.6 and 0.9 per cent,
      respectively. Analysis of the operative interventions according to risk group,
      stage of disease and histopathological findings shows that there is no
      significant difference in lethality, but there is a higher rate of relapses among
      patients treated with total thyroidectomy.

PMID- 9173174
TI  - [Problems of postoperative drug analgesia in proctological surgery].
AB  - It is the purpose of this study to analyze all practical methods of analgesia in
      proctologic surgery. A new procedure of intravenous or subcutaneous fentanyl
      analgesia is proposed.

PMID- 9173175
TI  - [Dermatofibrosarcoma protuberans--a clinico-anatomical and immunohistochemical
      study].
AB  - This is a report on the clinical, anatomical and immunohistochemical study of
      thirty patients presenting dermatofibrosarcoma protuberans. Its incidence (4.8
      percent), covering a 15-year period in a specialized oncological unit, wider age
      range and high rate of relapses (66.6 percent) are established as the result of
      clinical and anatomical revision. The latter findings necessitate radical removal
      of the neoplasm as early at its primary resection. The practical implications of
      the so-called "spoke-like" structures, pathognomonic for histological
      identification of the tumor, are discussed. The immunohistochemical study for
      S100 [correction of C100] protein and lysozyme is negative, while alpha 1
      antitrypsin reaction is positive in single rounded histiocyte-like cells which is
      by no means a conclusive evidence of the phenotype characteristics of the cell
      population in dermatofibrosarcoma protuberans.

PMID- 9173176
TI  - [The multiple organ failure syndrome--its pathophysiology and treatment].
AB  - Polyorganic deficiency syndrome (PODS) is a generalized response to the effect of
      a variety of agents hardly lending itself to control, becoming manifest with
      rapid proliferation within the body. The issues discussed include: epidemiology
      with a special reference to panendothelial trauma to pulmonary and other systems
      with impairment of oxygen utilization by the cells, microcirculation disorders,
      mediators, ARDS development, disturbed barrier function of the intestinal mucosa,
      enhanced glutamine consumption with ensuing villous atrophy. Symptoms presented
      by various organs, treatment consisting in block of stimulation and block of
      mediators, as well as selective decontamination and adequate diet are also dealt
      with. Against the background outlined above the prognostic point rating system
      (the so-called score rating) of PODS with simultaneous application of the APACHE
      III rating system are evaluated. Age-related factors and number of organs
      involved are likewise considered.

PMID- 9173177
TI  - [The views and attitudes of the Clinic of Emergency Surgery of the Clinical
      Emergency Medical Center at the Queen Ioanna State University Hospital on the
      potentials of surgical endoscopy in upper digestive hemorrhages].
AB  - Transendoscopic sclerotherapy of esophageal varix in children and adults is
      introduced in the clinic of emergency surgery ever since 1973. In children aged 3
      to 14 years presenting preportal block a 100 per cent survivorship is recorded 20
      years after the manipulation. The outcome of endoscopy in adult patients is
      successful in 57.69 per cent. Perilesional sclerosing is introduced in the CES in
      1982, with a complete and definitive hemostasis attained in 46.7 per cent of the
      cases. In 1983, transendoscopic electrocoagulation is practically implemented in
      the CES, with the rate of successfully cured amounting to 55.49 per cent. Having
      in mind the limitations and contraindications of therapeutic transendoscopic
      hemostasis in massive hemorrhages, particularly those of ulcerative origin,
      preference is given to the safer hemostasis by surgical means.

PMID- 9173178
TI  - [A malignant rhabdoid tumor of the soft tissues].

PMID- 9173179
TI  - [Lipoma of the stomach--clinically progressing as pyloric stenosis].

PMID- 9173180
TI  - [Paragangliomas in the head and neck area].

PMID- 9173181
TI  - Cardiovascular effects of ethanolic and aqueous extracts of Pimenta dioica in
      Sprague-Dawley rats.
AB  - The hypotensive activity of ethanolic and aqueous extracts of Pimenta dioica and
      several fractions of the aqueous extract was observed in anaesthetized
      normotensive rats. General effects of the extracts and fractions were assessed
      through Hippocratic screening showing a central nervous system (CNS) depressant
      effect. The intravenous (i.v.) administration of the aqueous extract of Pimenta
      dioica (30, 70, 100 mg/kg) produced a dose-related significant fall in mean
      arterial blood pressure (MAP). The ED50 was 53.94 mg/kg. The hypotensive effect
      of identical doses (100 mg/kg) of the aqueous extract (95% decrease) was
      significantly greater (P < 0.05) than the effect of the ethanolic extract (67%
      decrease). The final aqueous fraction produced the greatest hypotensive activity
      compared to the other fractions of the total aqueous extract. There were no
      significant changes in the heart rate and no abnormalities were observed in the
      EKG. The mechanisms of action of the extracts have not been determined.
      Structural elucidation of the compounds responsible for this activity is under
      investigation.

PMID- 9173182
TI  - [The field of migration medicine is more and more important. Responsibility of
      primary health care for refugees' health requires more knowledge].

PMID- 9173183
TI  - [Income tax 1997. Adaptation to the EEC and a new and old income tax reduction].

PMID- 9173184
TI  - [Development of activities within health care services: industrial models are
      seldom adapted].

PMID- 9173185
TI  - [An "epoch making" study on gallbladder surgery is questioned].

PMID- 9173186
TI  - [The National Board of Health and Welfare and a county council were not approved
      by quality control].

PMID- 9173188
TI  - [Lung cancer. A therapeutic challenge].

PMID- 9173187
TI  - [Truth or lies about snuff].

PMID- 9173189
TI  - [Anaphylaxis in severe food allergy. Adrenaline injection is safer than
      inhalation].

PMID- 9173190
TI  - [Increased use of antidepressive agents. A correctly aimed development].

PMID- 9173192
TI  - [Surgical resection of lung cancer. Supplemented with radiotherapy and
      chemotherapy may improve the therapeutic results].

PMID- 9173191
TI  - [In spite of the long way to reach optimal treatment and prevention. Increased
      knowledge of lung cancer biology].

PMID- 9173193
TI  - [Trophoblastic diseases. Pathological concepts and genuine neoplasias].

PMID- 9173194
TI  - [Interns' presence during consultations in ambulatory psychiatric care. An
      ethical dilemma].

PMID- 9173195
TI  - [STRAMA--with the hold of antibiotic resistance. High tempo of local activities
      yields good results].

PMID- 9173196
TI  - [PC-resistant pneumococci are increasing in Skane. Fewer and fewer children
      receive antibiotics--is there a cause?].

PMID- 9173197
TI  - [Do ecological risks stop registration? It is reasonable to discuss the impact of
      antibiotics on the environment].

PMID- 9173199
TI  - [A comment (2): physician-patient meeting is the basis in the art of medicine].

PMID- 9173198
TI  - [If male medical students are lacking empathy (1): introduce supportive
      training!].

PMID- 9173200
TI  - [APC resistance, oral contraceptives and thrombosis. Screening is justified for
      diagnosing high-risk cases].

PMID- 9173201
TI  - [Agents, methods and environments against suicide].

PMID- 9173202
TI  - [Diagnosis has moved into the picture].

PMID- 9173203
TI  - [Occurrence of immune hyperthyroidism after radioiodine therapy of autonomous
      goiter].
AB  - AIM: The goal of the study was to examine the prevalence of Graves' disease
      following I-131 treatment of autonomous goiter with special regard to
      pretreatment scintigraphic patterns. PATIENTS AND METHOD: Pre- and posttreatment
      in-vitro and in-vivo parameters were studied in 375 consecutive patients treated
      with I-131 therapy for nodular or diffuse autonomous goiter. All patients
      included were within ambulant control for at least 2.5 months following
      treatment. According to the pretreatment Tc-99m pertechnetate scan 59% (220/375)
      had multifocal (MF), 23% (86/375) unifocal (UF), 10% (38/375) mixed focal
      disseminated (FD) and 8% (31/375) disseminated (D) scintigraphic patterns.
      RESULTS: In 93.9% (352/375), the autonomous tissue was totally, in 2.1% (8/375)
      partially and in 1.6% (6/375) insufficiently eliminated. In 2.4% (9/375) a
      relapse of hyperthyroidism was observed 2 to 10 months following I-131 therapy.
      In 8 patients a relapse of hyperthyroidism was accompanied or followed by an
      elevation of the previously non-elevated TSH-receptor antibody (TRAb) level and
      in 1 patient by an TRAb increase to the upper borderline range implicating
      Graves' disease. With the prevalence of Graves' disease following I-131 therapy a
      statistically significant difference in pretreatment Tc-99m pertechnetate
      scintigraphic patterns was found: 0% of unifocal (0/86) or multifocal (0/220),
      however 18% (7/38) of focal-disseminated and 7% (2/31) of disseminated
      scintigraphic patterns. From the 366 patients without relapse of hyperthyroidism
      2 (MF) had elevated pre- and posttreatment TRAb levels and 3 (D) had elevated
      TRAb levels for the first time after I-131 therapy. CONCLUSION: There is a low
      overall prevalence (2.4%) of Graves' disease following I-131 therapy for nodular
      or diffuse autonomous goiter. However, the prevalence of posttreatment Graves'
      disease is highly dependent upon pretreatment scintigraphic patterns exhibiting
      focal-disseminated or disseminated patterns.

PMID- 9173204
TI  - [Clinical value of somatostatin receptor scintigraphy. Studies of pre- and
      intraoperative localization of gastrointestinal and pancreatic tumors].
AB  - BACKGROUND: [111In-DTPA-D-Phe1]-pentetreotide scintigraphy is able to detect
      neuroendocrine tumors not shown by radiological methods. PATIENTS AND METHODS: In
      270 patients with neuroendocrine gastroenteropancreatic tumors (GEP tumors) 400
      somatostatin receptor scintigraphies were performed. 70 patients (38 female, 32
      male, aged 28 to 74 [56 +/- 12.6] years) underwent surgery and follow-up over 2
      years. The aim of the present study was the comparison of preoperative
      somatostatin receptor scintigraphy with radiological methods (sonography, CT) and
      intraoperative localization of GEP tumors with a hand-held gamma-probe. RESULTS:
      Somatostatin receptor scintigraphy was successful in localizing primary tumors in
      all patients. Liver- and lymph node metastases could be visualized with a
      sensitivity of 94 and 95 percent. In 7 patients 35 lesions could be identified by
      intraoperative tumor localization using a hand held gamma probe. Radiological
      methods identified only 11, surgical palpation 15 and preoperative somatostatin
      receptor scintigraphy 27 lesions. CONCLUSION: Somatostatin receptor scintigraphy
      improves detection of small and occult GEP tumors. Intraoperative probe counting
      with a hand-held gamma probe can identify tumors even when they are small and
      impalpable, but receptor positive.

PMID- 9173205
TI  - [Mediastinal spreading and aortic insufficiency].

PMID- 9173206
TI  - [Differential diagnosis of acute migraine attacks].

PMID- 9173207
TI  - [Therapy of hepatitis C].
AB  - The purpose of this review is an update of the therapy of hepatitis C especially
      with Interferon-alpha. From the large number of publications on this topic the
      established facts were worked out. Taking these facts as a base guidelines for
      the therapy in practical use were defined. In addition the aspects of therapeutic
      strategies of chronic hepatitis C which until now can not definitely be judged
      are discussed. In the relatively few patients in whom hepatitis C is diagnosed
      already in the acute phase, Interferon-alpha-treatment (3 x 3 million units 3
      times a week) for 3 to 4 months increases the percentage of patients in whom HCV
      RNA in the serum is eliminated. In patients with chronic hepatitis C, after
      decision finding for treatment, a standard scheme is recommended which consists
      of a monotherapy with recombinant Interferon-alpha. The dosage of Interferon
      alpha is in the first 12 to 16 weeks 5 up to 6 million units given 3 times a
      week. For the further therapy 3 million units 3 times a week seems to be
      appropriate. The recommended duration of Interferon-alpha-therapy is 12 months. A
      long-term benefit of about 20% can be achieved in unselected groups of patients
      when judged on the permanent normalisation of serum transaminases and elimination
      of HCV-RNA in the serum. Important factors which may influence the probability of
      a sustained response, like HCV genotype, virus titer in serum, duration of the
      disease, high hepatic iron content and the presence of cirrhosis, are discussed.
      Up to now there exist no reliable guidelines in the case of a "no change"
      situation and for patients with a flare-up of inflammatory activity during or
      after therapy. Combination therapy of Interferon-alpha with other drugs like
      analogous of nucleotides (for example ribavarin), non steroidal antirheumatic
      drugs and ursodesoxycholic acid (UDCA) have still to be evaluated in controlled
      clinical trials.

PMID- 9173208
TI  - [Moraxella catarrhalis: virulence and resistance mechanisms].
AB  - It is more than a century ago that Moraxella catarrhalis was discovered and
      described in some detail. However, it was not until the last decade that M.
      catarrhalis was recognized as a facultative pathogen, namely in otitis media
      (predominantly in children), sinusitis and nosocomial pneumonia in the group of
      elderly, debilitated patients. Liberation of endotoxin, histamine, and
      chemotactically active factors can be considered the major pathogenicity factors.
      The pathogen can protect itself, on the one hand by binding of the Clq
      subcomponent of the complement system followed by subsequent formation of a
      functionally inactive complex with Cl, and on the other hand by inactivation of
      the terminal (lytic) complement complexes by means of a specific protein on the
      surface of the outer cell wall. Routine diagnostic procedures require, above all,
      culture of the pathogen: up to now the detection of specific IgA-antibodies has
      not been routinely available. More than half of the clinical isolates are known
      to exhibit beta-lactamase production (BRO-enzymes). This is the reason why
      combinations of a penicillin compound with a beta-lactamase inhibitor, the group
      of the newer cephalosporins (including the orally active ones), doxycycline and
      the macrolides are therapeutically effective.

PMID- 9173209
TI  - [Value of various intra- and extraoral therapeutic procedures for treatment of
      obstructive sleep apnea and snoring].
AB  - BACKGROUND: Recently intra- and extraoral devices are increasingly used in order
      to treat obstructive sleep apnea (OSA) and snoring. We examined the value of some
      devices according to the literature and our own results. PATIENTS AND METHODS:
      The mandibular advancing devices aim at increasing upper airway diameter. The
      active part of the tongue extending device (SnorEx) is a stamp connected to a
      piston which exerts pressure at the base of the tongue causing its forward
      displacement; we studied 23 patients. The principle of an optically stimulating
      system ("eye-cover", Snore-Stop) consists of a microphone and light diods which
      are integrated in the eye-cover. After detecting acoustic signals (for example
      snoring) optical stimuli are generated in front of the eyes, which are thought to
      induce arousals causing a change of body position and the reduction of the
      snoring and apneas; we measured 24 patients. The principle of the tongue-retainer
      (Snore-Master) is the fixation of the tongue in a ventral position, which is
      thought to enlarge the mesopharyngeal area; we studied 14 patients. The nose
      plaster (Breathe-Right) contains an elastic spine that pulls the alae nasi
      cranial. This manipulation is thought to increase the diameter of the nostril and
      reduce the airway resistance. We measured 30 patients with obstructive sleep
      apnea and 20 snoring subjects without obstructive sleep apnea. RESULTS: Regarding
      the mandibular advancing due to different appliance designs and study protocols
      variable success rates have been documented. In patients with mild to moderate
      obstructive sleep apnea a reduction of the sleep related breathing disorder could
      be shown. Non compliance (NC) to the tongue extending device was 75% (17/23). Non
      compliance-patients were characterized by unacceptable local-side-effects of the
      prosthesis, lacking improvement of symptoms and of the respiratory disturbance
      index. Both tongue-retainer and -extensor are characterized by a high incidence
      of local side effects. Neither the eye-cover nor the nose plaster could improve
      the severity of obstructive sleep apnoe or snoring. In contrast to another study
      we could not show a significant effect of the tongue-retainer. CONCLUSIONS:
      Neither the nose plaster nor the optical stimulating device influenced the degree
      of obstructive sleep apnea and snoring. There are conflicting data regarding the
      tongue retainer. The high rate of non-compliant subjects and the low efficacy of
      the tongue extending prosthesis precludes large-scale use of this treatment
      modality in patients with obstructive sleep apnoe and snoring. In selected
      individuals suffering from a mild to moderate degree of obstructive sleep apnea
      with CPAP-inefficiency and -incompliance the mandibular advancing principle may
      be an therapeutic alternative to CPAP.

PMID- 9173210
TI  - [Alstrom syndrome--a rare disease of diabetic association].
AB  - BACKGROUND: Alstrom's disease is a rare hereditary multiple-system illness,
      whereas a second-messenger defect can be assumed. CASE REPORT: We describe a case
      the first in Germany of 15 known cases in the world literature-, who suffers from
      all clinical features, such as non-insulin-dependent diabetes mellitus, retinitis
      pigmentosa, pancochlear damage of the ears, hypogonadism, obesity and chronic
      nephropathy, with the exception of acanthosis nigricans. CONCLUSION: Because of
      the multiplicity of affected organs the diagnosis of Alstrom's disease is
      difficult.

PMID- 9173211
TI  - [Comparative study of the effects of rotating instruments on the dental surface].
AB  - This study analyses the relationship between the use of rotating instruments, the
      production of a smear layer and the presence of alterations to enamel
      microstructures. The rotating instruments used were carbide (8-12 blade) and
      diamond tipped (30-15 m) cutters. Cavities were made in extracted teeth.
      Subsequently, half the sample was analysed using the rugosimeter before and after
      the application of ortophosphoric acid at 35% for 15 and the other half suing a
      Scansion Electronic microscope (SEM). The results obtained showed on the one hand
      that carbide cutters leave a smoother surfacer than diamond tipped cutters, and
      on the other that the smear layer is eliminated better by carbide cutters
      compared to diamond tipped cutters. Moreover, there are no major traumatic-type
      alterations at the level of the enamel affecting the microstructure after the use
      of carbide cutters.

PMID- 9173212
TI  - [Diagnostic-therapeutic protocol in orthodontic surgery].
AB  - The authors describe the diagnostic-therapeutic protocol of orthodontical
      surgical treatments of Angle-class I, II and III used by the Oral and Maxillo
      Facial Surgery Department of Second University of Naples. They also present a
      personal survey.

PMID- 9173213
TI  - [Dento-skeletal recurrence in cases of surgical treatment of dysmorphism].
AB  - The purpose of the present study is to investigate the factors contributing to
      skeletal relapse after surgical correction of mandibular prognathism.
      Postoperative follow-up after mandibular setback is carried out to clarify the
      timing and causes of the relapse. The subjects are mandibular prognathism
      patients. The etiology of relapse is discussed.

PMID- 9173214
TI  - [Management of facial pain resulting from cancer in oral and maxillofacial
      surgery].
AB  - Pain, which is among the most prevalent symptoms experienced by cancer patients,
      must absolutely be treated. The most important biologic effects of this sort of
      pain plays on patients' psychosociality. This is in reference to the quality of
      pain, the amount of pain and to the character of the patients. Actually, pain
      only in appearance is presented as a symptom; it is usually a disease. Patient
      assessment, the use of anticancer therapies and systematically administered non
      opioid and opioid analgesics are pivotal. Practical aspects of cancer pain
      treatment include both drug selection, method of analgesic administration:
      selection of the appropriate route, dose titration and an understanding of the
      management of side effects. Pain therapy includes another series of possibilities
      like the use of adjuvant analgesics, psychological therapies, physiatric
      techniques and invasive interventions such as the use of intraspinal drugs,
      neural blockade and neuroablative techniques. This kind of therapy must be
      employed at all times, whether the case may be resolved surgically or not. So we
      think that pain can be effectively treated. This study was carried out to obtain
      the correct therapeutic approach for facial cancer pain syndrome. The research
      was performed on seven women and thirteen men with a mean age of 58 years. All
      the patients' clinical appearances were standardized with care. Study
      participants included odontostomatologists and anesthesiologists with experience
      of controlling cancer pain. The sensation of pain was quantified by means of the
      Visual Analogue Scale (VAS) while their psychosocial ability was assessed with
      the Karnofsky Performance Scale (KPS). In this way the authors hoped to obtain a
      good quality of standardization. The study was performed for a period of two
      months. The conclusions are that Trans Epidermis Nervous Stimulation (TENS)
      offers positive results for variable periods and only in 60% of patients with a
      low level of pain. The use of antiphlogistic non-steroid drugs and of opioid
      drugs, with a particular management requested from the personal clinical status
      of each patient, result as being the most effective therapeutic resource. Such
      therapies must be employed, whether the case may be resolved surgically or not.
      Nevertheless it is necessary to realize that drugs or other therapies for cancer
      pain are independent and propaedeutic to each surgical approach. Finally, the use
      of opioids is addressed in the management of patients with pain that is
      refractory to other interventions. This approach can provide adequate relief to
      the vast majority of patients. We find the morphinomania risk in cancer pain
      patients is not scientifically wellfounded.

PMID- 9173215
TI  - [Histomorphology of secondary cartilage in human fetal mandibles].
AB  - The aim of this study was to provide a histomorphological analysis of some
      secondary cartilages of mandible and temporal bone as observed in human fetuses
      18-22 weeks old. The behavior of cartilage was studied in both these regions,
      which were decalcified, cut at 10 mu, stained with Mallory staining and examined
      by optical microscopy. In mandible symphysis menti and condylar cartilage were
      described. The symphysis appeared to be formed by a fibrous cartilagineous
      structure surrounded by membranous bone. This structure seems be round in the
      caudal sections and ovoidal in the rostral sections with the major axis
      perpendicular to the mean sagittal plane. Meanwhile the condyle is formed by
      secondary cartilage which may be appreciated in this development stage 5 zona.
      Secondary cartilage was observed also in the temporal bone nearby the primitive
      glenoid fossa. The development and the importance of these cartilagineous
      structures are discussed.

PMID- 9173216
TI  - [Necessity and validity of standard models for experimental preclinical
      evaluation of biomaterials. An example of biologic characterization of a
      hydroxyapatite-based implant material].
AB  - A large number of methods are now available for the preclinical screening of
      implantable materials concerning their biocompatibility and their ability to
      stimulate tissue formation. In vitro techniques represent a very useful tool,
      since this way we can realistically simulate the biological events which occur in
      vivo at the bone-implant interface. In the present study scanning electron
      microscopy and light microscopy observations were performed in order to assess
      the effect of an hydroxyapatite granulate on cell behaviour and morphology.
      Uptake of proteins to hydroxyapatite surface has been also investigated by
      comparing the amounts adsorbed after incubation with bovine serum albumin and
      bovine pancreaticamilase. According to our preliminary observation cells do not
      show signs of toxicity or inhibition of cell growth even after 14 days of co
      culture with hydroxyapatite. Granules were covered by an uninterrupted cell layer
      by day seven. Even after two days micrographs show cells anchored and spread over
      the surface of the underlying granules, with a flattened and stellate shape. Such
      a morphology indicates a very high cellular activity, suggesting that the
      interaction with hydroxyapatite seriously increased metabolism. Measurements of
      protein adsorption on the hydroxyapatite surface show that changes in the size of
      particles affect the binding of proteins, while, in the case of granular
      hydroxyapatite, despite changes in size of granules, variations of protein
      adsorption were not observed, neither in relation to their different isoelectric
      point. Our preliminary results represent a good example of the opportunities
      presented by an experimental in vitro model.

PMID- 9173217
TI  - [Management of patients with coagulation defect in oral and maxillofacial
      surgery. I. Management of patients with drug-induced hypocoagulation].
AB  - Odontoiatric problems, clinical and surgical, connected with defective
      coagulation, are very frequent. Such cases can be divided into two groups: in the
      first we find patients with iatrogenic coagulopathy while in the second we find
      patients with hypocoagulative diseases. In this article the authors present the
      result of several years of research carried out to obtain a correct clinical and
      therapeutic approach for clinical and surgical Odontostomatology. After an
      introduction on clinical pharmacology and the use of anticoagulants, the
      principal clinical cases are discussed. Various laboratory tests evaluating
      patients with pharmacological coagulopathy are examined. The most specific and
      significant tests are illustrated following up the authors experiences. In the
      last part the authors illustrate cases corresponding to the two serious and
      frequent complications that can be found in patients with iatrogenic
      coagulopathy: hematorrhea and thromboembolism. These matters were dealt with from
      an Odontostomatologic point of view. The results obtained suggest the necessity
      of keeping to the management that was described. Actually a low percentage of
      accidents occurred only when the above-mentioned clinical processes were
      completely performed.

PMID- 9173218
TI  - [Management of patients with coagulation disorder in oral and maxillofacial
      surgery. I. Management of patients with hypocoagulation caused by primary
      thrombocytopathy].
AB  - Any oral and maxillo-facial surgical treatment, however urgent it may be, must
      not include pathological states in which the patient's life may be particularly
      at risk as, for example, with Disseminated Intravascular Coagulation (DIC) or
      throm-botic thrombocytopenic purpura. In this article the authors present the
      result of studies carried out on the nosology of thrombocytopathy from an
      odontostomatological point of view. Thrombocytopathy can be divided into two
      groups: the first including the pathologies with a predominant defective number
      of thrombocytes (i.e.: thrombocytopenia, thrombocythemia, thrombocyto-sis), the
      second including forms with predominant qualitative defects (commonly known as
      thrombocytopathies). The authors, after having presented in short the
      physiopathologic functions of thrombocytes, illustrate the clinical and
      therapeutic aspects of the most important thrombocytopathies. Morbus Maculosus
      Werhofii, Glanzmann's disease, Bernard-Soulier syndrome, thrombocytopathies from
      defective reaction of release, Thrombocytopathies from defective procoagulant
      activity of blood plaques, thrombocytopathies in linkage to other genetic
      anomalies, von Willebrand's pseudodisease and a lot of acquired
      thrombocytopathies are identified. In the last part the authors illustrate the
      most opportune clinical steps corresponding to the most important
      thrombocytopathies. The results obtained suggest the necessity of keeping to the
      management that was described, Actually a low percentage of accidents occurred
      only when the above-mentioned clinical processes were completely performed.

PMID- 9173219
TI  - [The characteristics of third-molar development in children from 2 geographic
      areas of Croatia].
AB  - BACKGROUND: The development differences of wisdom teeth in children in two
      geographical regions of Croatia (Istria and Slavonia) have been studied. METHODS:
      One thousand orthopantomograms have been analyzed (Istria: 574-280 boys and 294
      girls; Slavonia: 426-210 boys and 216 girls); they were carried out in children
      aged from 6 years and 6 months to 12 years and 6 months, divided into six groups.
      All of them presented the following criteria: absence of numerical anomalies of
      permanent teeth (wisdom teeth not included), absence of extraction of permanent
      teeth and of different syndromes. The development of wisdom teeth was assessed by
      Gat's method. RESULTS: The development of wisdom teeth begins earlier in Istrian
      subjects, but in both groups the wisdom tooth crypt appeared also after the 12
      years and 6 months. The greatest increase is frequency of wisdom teeth germ in
      both groups was observed in children aged between 9 or 10 years. Most of Istrian
      children, compared with those in Slavonia, had wisdom teeth germs. As to jaw
      differences, it was observed that children in Istria (except the group of those
      11 years old) have significantly more wisdom teeth germs in the mandible (p <
      0.01). Significant jaw differences were found only in the group of 8-years-old
      Slavonian children. The differences in presence of wisdom teeth between males and
      females and sites of each jaw were not found to be significant.

PMID- 9173220
TI  - [Etiopathogenic hypotheses on dental ankylosis].
AB  - The authors review the literature about the different etiopathogenetic hypotheses
      of tooth ankylosis. They classified the ankylosis in three big groups: traumatic
      ankylosis due to direct and indirect injuries to the tooth, iatrogenic ankylosis
      due to unadvised maneuvers made by the dentist, and atraumatic ankylosis. The
      last is the most important group caused by metabolic problems and with family
      characteristics. Furthermore they underline the important role played by GAG and
      corresponding lytic enzymes in the development of atraumatic ankylosis. They
      described, the therapeutical procedures to be used in the different cases. The
      clinical cases presented are representative of the different therapeutical
      approaches.

PMID- 9173221
TI  - [Treatment of the patient with a coagulation defect in oral and maxillofacial
      surgery. III. The management of patients in a hypocoagulative state because of a
      hemophilic-type primary pathology].
AB  - Hemophilia plays a particularly important role among the diseases caused by
      abnormal coagulation. Defective blood-clotting factor diseases have a particular
      importance between coagulopathies: hemophilia, among these hematic disorders,
      plays a principal role. In this paper the authors present the results of
      scientific research on hemophilic disease carried out to obtain a correct
      clinical and therapeutic approach for clinical and surgical Odontostomatology.
      The authors, after having presented in short the physiopathologic function of
      coagulation factors, illustrate the clinical and therapeutic aspects of
      Hemophilia A and Hemophilia B. The correct Odontostomatological and Maxillo
      Facial Surgical approach is presented as the result of the authors' research.
      Also von Willebrand's disease is illustrated even if it is not exactly a
      hemophilic disease. This is because all hemophilias must produce a gynephoric
      inheritance pattern. Nevertheless clinical, therapeutic and molecular biology
      appearance suggests the illustration of von Willebrand's disease together with
      hemophilias. Von Willebrand's disease can be divided into three nosologic groups
      and to each one corresponds a particular clinical and therapeutic management.
      Such cases are illustrated and examined from an Odontostomatologic point of view.
      The results obtained suggest the necessity of keeping to the management that was
      described. Actually a low percentage of accidents occurred only when the above
      mentioned clinical processes were completely performed.

PMID- 9173222
TI  - [The role of the general practitioner and dentist in the early diagnosis of
      preneoplastic and neoplastic lesions of the oral cavity].
AB  - Early detection of oral cancer allows for a 90% 5-year survival rate.
      Unfortunately, nowadays 60% of these tumors are detected in advanced stages with
      a 5-year survival of about 20%. Therefore, early diagnosis is of the greatest
      importance. Both the GP and the dentist have a primary role in early diagnosis
      and are also responsible for informing the population regarding the risk factors
      in oral cancer. GPs and dentists should systematically check the oral cavity
      mucous membranes in heavy smokers and/or drinkers above all when over 40. Lesions
      become suspicious when they persist for more than two weeks after detection. The
      high-risk pts and suspicious lesions should undergo the following diagnostic
      procedures: micronucleus test, vital staining, scraping and biopsy for
      cytological and histological examination. The above mentioned methods will
      increase the early diagnosis of tumours and improve its prognosis.

PMID- 9173223
TI  - [Dental and oral aspects in pediatric liver transplant patients. A comparison
      between the effects of cyclosporine A and FK 506].
AB  - The evolution and the improvement of the surgical techniques and pharmacological
      therapies brought to new patients categories, also in odontoiatric field for
      example patients who underwent organ transplantation. Among the patients, we
      wanted to dwell our attention on pediatric patients after liver transplantation,
      by light of the new therapeutic outlines modifications. In fact in these young
      patients it is possible to observe, besides the severe systemic consequences,
      also the involvement of the oral cavity. After the transplantation, the
      immunosuppressive therapy is set up and it is based on the use of cyclosporine
      with the possible azotiopine or steroid association. The cyclosporine side
      effects are well known and, among these, the gingival hyperplasia. FK506 is a
      drug recently introduced, it is a strong immunosuppressor. Therefore we began to
      estimate patients who assumed FK 506, in order to compare the effect at the
      gingival level among patients who follow a cyclosporine therapy.

PMID- 9173224
TI  - [Dissection of the cranial base en bloc with the infratemporal fossa].
AB  - A high incidence of morbidity and mortality was related with skull-base neoplasm
      surgery. Several advances have permitted, in recent years, the total excision of
      such neoplasms with minimal patient morbidity. Due to an improved understanding
      of the surgical anatomy of the skull-base and to the collaboration of the
      neurosurgeon and maxillofacial surgeon and, moreover, to the improvements of
      imaging (CT and MR) in the past decades new combined approaches were planned and
      performed to allow en bloc resections of extensive lesions. Extensive exposure of
      the tumor, improved management of the internal carotid artery, preservation of
      cranial nerves not involved by tumors and improved cranial base reconstruction
      techniques (by free flaps) have resulted from this progress. The aim of the
      present work is to show the main anatomical landmarks of infratemporal fossa and
      medium skull base that help the surgeon to achieve an en bloc resection.

PMID- 9173225
TI  - [A longitudinal evaluation of the reliability of a growth forecast in a sample of
      an untreated population].
AB  - The aim of this study is to verify by a longitudinal study the reliability of
      growth forecast on a homogeneous Italian female sample. A cephalometric software
      was used and the result was enough reliable, especially in short term forecast.
      However, a constant tendency of the program to construct a forecast in
      hyperdivergency was found.

PMID- 9173226
TI  - [A statistical epidemiological study of a possible correlation between serum
      transaminase levels and viral hepatic pathology markers and lichen planus orale].
AB  - The aim of the present study is to carry out a clinical-statistical research into
      a large number of patients suffering from oral lichen planus (LPO) and from
      different odontostomatologic pathologies. In both groups of patients serum
      transaminase values and eventual presence of hepatopathy viral markers were
      investigated in order to identify a possible correlation between the aforesaid
      parameters and LPO, considered in its various clinical forms (papular and erosive
      essentially). Results had showed a close association between hepatopathy and LPO,
      according to results of studies performed by other Italian and Spanish groups and
      differently from Anglo-Saxon authors: above all an increased incidence of C
      hepatitis in patients with lichen was observed. Furthermore our investigation is
      agreed in underlining the great importance to attach to erosive form of oral
      lichen, that seems to join to active chronic hepatitis most frequently than
      papular one.

PMID- 9173227
TI  - [Cytoprotective effect of trehalose in cryopreservation of isolated cardiac
      myocytes].

PMID- 9173228
TI  - [Experimental study on myocardial edema and cardiac lymph in the preserved heart-
      effect of hyaluronidase].

PMID- 9173229
TI  - [Electron-conformational interactions and significance of effective charges on
      atoms in peptides].

PMID- 9173230
TI  - [Receptor-mediated transport of biologically active substances into cells using
      recombinant human growth hormone].

PMID- 9173231
TI  - [Induction of suppressor activity in allospecific cytotoxic T-lymphocytes].

PMID- 9173232
TI  - [Effect of reverse transcriptase inhibitors on telomerase function in immortal
      murine fibroblasts].

PMID- 9173233
TI  - [Interaction of influenza virus matrix protein M1 with histones].

PMID- 9173234
TI  - [The protein environment of a template in the decoding region from data on
      affinity modification of ribosomes from human placenta by an alkylating
      derivative of the oligoribonucleotide pGUGU3].

PMID- 9173235
TI  - [Nucleotide residues of 18S rRNA, located near the decoding segment on human
      ribosomes, from data on affinity modification of 5'-derivatized
      oligoribonucleotides, containing codon AUG].

PMID- 9173236
TI  - [Diagnosis of genetic mutations using oligonucleotide microchips].

PMID- 9173237
TI  - [Telomerase, aging, cancer].

PMID- 9173238
TI  - [Evolution of a fragment of the mitochondrial DNA cytochrome B gene from some
      Baikalian and non-Baikalian species of Cottus fish].

PMID- 9173239
TI  - [Properties of free and hidden natural antibodies, reacting with DNA and
      cardiolipin].

PMID- 9173240
TI  - [Theoretical study of the spatial structure of the Ala-Ser-Thr-Thr-Thr-Asn-Tyr
      Thr segment of the HIV gp120 protein, responsible for binding of the virus with
      the T-cell T4 receptor].

PMID- 9173241
TI  - [Localization of the antigenic determinant of human pancreatic cholesterol
      esterase in proline-rich repeats].

PMID- 9173242
TI  - [A combinatorial algorithm for highly specific recognition of protein-coding
      regions in DNA sequences from higher eukaryotes].

PMID- 9173243
TI  - [Analysis of phylogenetic interactions of Baikal endemic amphipods (Crustacea,
      Amphipoda) based on comparing nucleotide sequences of parts of the mitochondrial
      gene for cytochrome oxidase subunit III].

PMID- 9173244
TI  - [Sequences of human chromosome 19 with partial homology to the human
      immunodeficiency virus type 1 genome].

PMID- 9173245
TI  - [Isolation of a protein, specifically binding with a triplet repeat of the (CTG)n
      type].

PMID- 9173246
TI  - [A model prokaryotic promoter. V. Footprinting E. coli RNA polymerase complex
      with constructs containing Pribnow sequence repeats].

PMID- 9173247
TI  - [Catalytic antibodies].

PMID- 9173248
TI  - [Polymorphism of the insertion/deletion type in the angiotensin-converting enzyme
      gene in normal subjects and among patients with vascular complications].

PMID- 9173249
TI  - [Determining contact sites of transcription factor NF-kappa B with DNA by
      regioselective covalent binding].

PMID- 9173250
TI  - [Structure-functional organization of Pseudomonas fluorescens genes, coding for
      biosynthetic enzymes of phenazine-1-carbonic acid].

PMID- 9173251
TI  - [Expression of the ribozyme gene in the recombinant defective adenovirus genome].

PMID- 9173252
TI  - [Study of the equilibrium interaction of DAM-DNA-(N-adenine)-methyltransferase
      from phage T4 with substrates and ligands by fluorescence quenching].

PMID- 9173253
TI  - [Mechanism of heat denaturation of muscle glycogen phosphorylase b].

PMID- 9173254
TI  - Adverse cerebral outcomes after coronary bypass surgery.

PMID- 9173255
TI  - Adverse cerebral outcomes after coronary bypass surgery.

PMID- 9173256
TI  - Adverse cerebral outcomes after coronary bypass surgery.

PMID- 9173257
TI  - Outcome of acute myocardial infarction according to the specialty of the
      admitting physician.

PMID- 9173258
TI  - Outcome of acute myocardial infarction according to the specialty of the
      admitting physician.

PMID- 9173259
TI  - Outcome of acute myocardial infarction according to the specialty of the
      admitting physician.

PMID- 9173260
TI  - Outcome of acute myocardial infarction according to the specialty of the
      admitting physician.

PMID- 9173261
TI  - Pamidronate and metastatic breast cancer.

PMID- 9173262
TI  - Pamidronate and metastatic breast cancer.

PMID- 9173263
TI  - Duration of mechanical ventilation.

PMID- 9173264
TI  - Duration of mechanical ventilation.

PMID- 9173265
TI  - Duration of mechanical ventilation.

PMID- 9173266
TI  - Prediction of liver fibrosis according to serum collagen VI level in children
      with cystic fibrosis.

PMID- 9173267
TI  - An unusual cause of dysphagia.

PMID- 9173268
TI  - Midtracheal stricture.

PMID- 9173269
TI  - Scrub typhus after a trip to Vietnam.

PMID- 9173270
TI  - A clinical trial comparing primary coronary angioplasty with tissue plasminogen
      activator for acute myocardial infarction.
AB  - BACKGROUND: Among physicians who treat patients with acute myocardial infarction,
      there is controversy about the magnitude of the clinical benefit of primary
      (i.e., immediate) coronary angioplasty as compared with thrombolytic therapy.
      METHODS: As part of the Global Use of Strategies to Open Occluded Coronary
      Arteries in Acute Coronary Syndromes (GUSTO IIb) trial, we randomly assigned,
      1138 patients from 57 hospitals who presented within 12 hours of acute myocardial
      infarction (with ST-segment elevation on the electrocardiogram) to primary
      angioplasty or accelerated thrombolytic therapy with recombinant tissue
      plasminogen activator (t-PA). We also randomly assigned 1012 patients to heparin
      or hirudin treatment in a factorial design. The primary study end point was a
      composite outcome of death, nonfatal reinfarction, and nonfatal disabling stroke
      at 30 days. RESULTS: The incidence of the primary end point in the angioplasty
      and t-PA groups was 9.6 percent and 13.7 percent, respectively (odds ratio, 0.67;
      95 percent confidence interval, 0.47 to 0.97; P = 0.033). Death occurred in 5.7
      percent of the patients assigned to angioplasty and 7.0 percent of those assigned
      to t-PA (P=0.37), reinfarction in 4.5 percent and 6.5 percent (P=0.13), and
      disabling stroke in 0.2 percent and 0.9 percent (P=0.11). At six months, there
      was no significant difference in the incidence of the composite outcome (13.3
      percent vs. 15.7 percent, P not significant) [corrected]. The primary end point
      was observed in 10.6 percent of the patients in the angioplasty group assigned to
      heparin and 8.2 percent of those assigned to hirudin (P=0.37). CONCLUSIONS: This
      trial suggests that angioplasty provides a small-to-moderate, short-term clinical
      advantage over thrombolytic therapy with t-PA. Primary angioplasty, when it can
      be accomplished promptly at experienced centers, should be considered an
      excellent alternative method for myocardial reperfusion.

PMID- 9173271
TI  - Treatment of ovarian cancer with intraperitoneal cisplatin.

PMID- 9173272
TI  - Treatment of ovarian cancer with intraperitoneal cisplatin.

PMID- 9173273
TI  - Treatment of ovarian cancer with intraperitoneal cisplatin.

PMID- 9173274
TI  - Hypertension in children.

PMID- 9173275
TI  - Hypertension in children.

PMID- 9173276
TI  - Implantable defibrillators in patients with coronary artery disease at high risk
      for ventricular arrhythmia.

PMID- 9173277
TI  - Implantable defibrillators in patients with coronary artery disease at high risk
      for ventricular arrhythmia.

PMID- 9173278
TI  - Nonbacterial thrombotic endocarditis in three members of a family.

PMID- 9173279
TI  - More on coronary-plaque rupture triggered by snow shoveling.

PMID- 9173280
TI  - How should doctors respond to their calling?

PMID- 9173281
TI  - Outcomes of medical-malpractice litigation.

PMID- 9173282
TI  - Outcomes of medical-malpractice litigation.

PMID- 9173283
TI  - Outcomes of medical-malpractice litigation.

PMID- 9173284
TI  - [Pfeiffer's disease, not always the innocent kissing disease].
AB  - Three patients, men of 39, 27 and 17 years old, who suffered from infectious
      mononucleosis (Pfeiffer's disease), presented with severe pain in the left upper
      abdomen radiating to the left shoulder (Kehr's sign). Ultrasonographically an
      increased amount of abdominal fluid was observed and the spleen ws slightly
      enlarged. Laparotomy revealed a ruptured spleen. This is a life-threatening
      complication of infectious mononucleosis.

PMID- 9173285
TI  - [Digoxin in chronic heart failure and sinus rhythm: is the end of the controversy
      in sight?].
AB  - It has for years been a matter of debate whether digoxin may/should be used in
      chronic heart failure with sinus rhythm. Interest in digoxin was renewed when it
      was found that the substance had a vagotonic as well as a sympatholytic effect in
      heart failure patients. A recent clinical trial led to the conclusion that
      although digoxin had no effect on the mortality among heart failure patients, it
      did lead to a reduction of the number of hospital admissions, particularly
      because of heart failure (indicating reduced morbidity and deceleration of the
      progression of the disease). Many heart failure patients continue to have
      symptoms in spite of treatment with diuretics and ACE inhibitors. As only few
      alternatives are available, many physicians in the near future will go on using
      digoxin in these patients- and as the recent study shows, rightly so.

PMID- 9173286
TI  - [Diagnosis and treatment of recurrent coughing and wheezing in children younger
      than 4 years old].
AB  - Recurrent coughing and wheezing occur in 10-20% of children younger than 4 years.
      Forty per cent of these children develop allergic asthma, while in 60% the
      symptoms are transient. It is difficult to distinguish between persistent and
      transient symptoms; signs of allergy and lack of symptom-free intervals are
      suggestive of persistent asthma. In acute wheezing and coughing a trial treatment
      with beta-2 sympathicomimetic agents is indicated, preferably using an inhalation
      aerosol with feed container; for cases with pronounced symptoms or strong
      suspicion of allergic asthma, high-dose oral corticosteroid treatment is
      recommended. Maintenance treatment with inhalation corticosteroids is valuable in
      moderately severe complaints of allergic asthma and in severe complaints about
      recurrent wheezing.

PMID- 9173288
TI  - [Musculoskeletal symptoms often incorrectly attributed to Lyme disease].
AB  - OBJECTIVE: To establish, in patients referred with persisting noninflammatory
      musculoskeletal complaints. diagnosed elsewhere with Lyme disease, whether Lyme
      disease was present. SETTING: Outpatient Clinic for Rheumatology. Eemland
      Hospital Amersfoort and University Hospital Utrecht, the Netherlands. DESIGN:
      Descriptive, prospective. METHOD: Patients were classified as having had Lyme
      disease in the past, having ongoing Lyme disease of no Lyme disease at all, on
      the basis of clinical history, physical examination, and classification criteria
      for Lyme disease. RESULTS: In a two-year period 37 consecutive patients (mean age
      50 years) were examined, 20 (54%) of whom had (a history of) Lyme disease. Of
      these 20, two suffered from erythema migrans, one of synovitis of the knee, and
      one of acrodermatitis chronica atrophicans (these four had not been treated).
      while one had persistent chronic oligoarthritis. Seventeen patients did not have
      Lyme disease, but were suffering from aspecific, noninflammatory musculoskeletal
      problems. CONCLUSION: In this patient group with persisting musculo-skeletal
      complaints, 'Lyme disease' had been diagnosed correctly as often as incorrectly.

PMID- 9173287
TI  - [Cancer incidence in the Schiphol area in 1988-1993].
AB  - OBJECTIVE: To calculate the cancer incidence in the region surrounding Schiphol.
      DESIGN: Descriptive epidemiological study based on cancer registry data. SETTING:
      Comprehensive Cancer Centre Amsterdam. The Netherlands. METHODS: Using noise
      levels expressed as Kosten-cenheden (Ke) of the air traffic around Schiphol
      (Amsterdam International Airport) as well as 4-digit postal code areas, two study
      areas were defined, a central area and an adjacent zone. All cancer cases
      diagnosed in 1988-1993 in the study areas were selected from the population-based
      Amsterdam Cancer Registry. Observed numbers of cancer cases were compared with
      expected numbers on the basis of national and regional cancer incidence rates.
      RESULTS: Cancer incidence (4535 cases) in 1988-1993 in the Schiphol region was
      slightly higher than national incidence rates (observed/expected (O/E) ratio:
      1.93; 95% confidence interval; 1.00-1.06) and almost equal to regional rates.
      This was largely due to relatively high rates for breast (O/E ratio: 1.08) and
      prostate (O/E ratio: 1.11) cancer in the Schiphol region as well as in the total
      area covered by the Amsterdam Cancer Registry. In addition, leukaemia,
      lymphoma/multiple myeloma and bladder cancer were more frequent, the last-named
      especially in males. The incidence of cancer of the respiratory tract was not the
      same in the central area and the adjacent zone. As compared with national rates,
      it was increased in the central area (O/E ratio: 1.19), while it was decreased in
      the adjacent zone (O/E ratio: 0.86). The incidence of cancer of all sites (O/E
      ratio: 1.10) was also increased in the central area, largely due to smoking
      related cancers. CONCLUSION: During 1988-1993, cancer incidence in the area
      surrounding Schiphol was a little higher than the national incidence rates and
      almost equal to the regional incidence. We could not demonstrate an association
      between air traffic and increased cancer risk. It is most likely that the
      differences for certain types of cancer as well as those between the two study
      areas were due to differences in lifestyle, such as smoking habits.

PMID- 9173289
TI  - [Borrelia lymphocytoma ('winter ears') in children].
AB  - Two cases of Borrelia lymphocytoma are reported. The skin lesions were located on
      the ear margin or lobe. They were swollen, red and painful on touching. Serum
      titres of antibodies to Borrelia burgdorferi were elevated in both cases.
      Spirochaetal cultures from skin biopsies taken from the lesions were
      unsuccessful. Both patients responded very well to antibiotic treatment.

PMID- 9173290
TI  - [Intra- and extramural workshop for care, teaching, and research].
AB  - Medical care and its development, education, training and research are closely
      linked in academic medical centres. Traditionally, hospital-based disciplines can
      make use of the university hospital as a 'workshop' for the combination of these
      activities. In the Netherlands, however, there is no structurally financed
      workshop for the non-hospital based medical disciplines, such as family medicine,
      public health medicine, and nursing home medicine. In the Academic Medical
      Centre, University of Amsterdam, an integrated hospital and primary health care
      oriented academic workshop is being developed, for all medical disciplines,
      including social medicine (e.g. preventive care) and general practice.

PMID- 9173291
TI  - [Did hypertension in The Netherlands decrease between 1974 and 1993?].

PMID- 9173292
TI  - [Passive smoking and lung cancer: a new report in perspective].

PMID- 9173293
TI  - [Good results of fasciotomy in chronic compartment syndrome of the lower leg].

PMID- 9173294
TI  - [Good results of fasciotomy in chronic compartment syndrome of the lower leg].

PMID- 9173295
TI  - [Incidence and treatment of prostatic carcinoma in the region of the Amsterdam
      Comprehensive Cancer Center, 1989-1994].

PMID- 9173296
TI  - [Hyperbilirubinemia in healthy full-term neonates: guidelines for diagnosis and
      treatment].

PMID- 9173297
TI  - [Future perspectives for children with spina bifida aperta].

PMID- 9173298
TI  - [Borderline or bipolar disorder after all?].
AB  - In two women aged 35 and 21 years, the initial diagnosis 'borderline personality
      disorder' was changed to 'bipolar disorder'. These disorders are separate
      entities with different therapy, but may resemble each other very much. It may be
      necessary to use heteroanamnesis and family anamnesis and to follow the patient
      for some time in order to establish whether there are mood disorders.

PMID- 9173299
TI  - [No routine antibiotic prophylaxis necessary in endoscopic retrograde
      cholangiopancreatography].
AB  - Acute cholangitis is a serious complication and cause of death in patients
      undergoing endoscopic retrograde cholangiopancreatography (ERCP). Some centres
      have adopted a policy of administering antibiotics before every ERCP procedure.
      The results of a recent clinical trial failed to support this policy. Antibiotic
      prophylaxis should be restricted to patients expected to develop incomplete
      drainage of the bile duct and to endocarditis prophylaxis.

PMID- 9173300
TI  - [Being raised by lesbian parents or in a single-parent family is no risk factor
      for problem behavior, however being raised as an adopted child is].
AB  - Modern reproductive techniques and alternative family structures (with single or
      homosexual parents and adoption situations) raise questions about the
      consequences for the growing children involved. Genetic links appear to be less
      important for the functioning of a family than a strong wish for parenthood;
      parents who have become parents only through great efforts display a better
      quality of parenthood than average natural parents. Characteristics of the
      parent/parents, such as paedagogic qualities, and the quality of the parent-child
      relationship appear more important than the type of family. Published results of
      research reveal no reason why lesbian families should be judged differently from
      heterosexual ones as family types for the raising of children. The main negative
      factor for the functioning of the child growing up in a single-parent family is
      the marriage conflicts that have led to the single-parent situation; being raised
      by a single parent in itself has no adverse effect. Raising adopted children from
      other countries makes far greater demands on the adoptive parents than parents of
      biological children have to meet. The raising of a foreign adopted child by a
      single parent entails additional risks for the child's development. Data on the
      development of children in alternative family structures frequently concern
      exceptionally competent parents, which may have biased the findings.

PMID- 9173301
TI  - [The value of a hand injury chart].
AB  - OBJECTIVE: To assess practicality, clinical merit and usefulness for scientific
      purposes of a hand injury chart in a hand surgery unit. DESIGN: Descriptive.
      SETTING: Academic Hospital Rotterdam-Dijkzigt, the Netherlands. METHODS: The
      records were examined of patients who within the period of one ear required acute
      surgical therapy for serious hand injuries (n = 148). Data concerning cause and
      extent of the damage to anatomical structures were recorded to evaluate accuracy
      in describing a hand injury with and without the chart. Time needed to study the
      patient record to ascertain sufficient details of the injury was noted in each
      case. RESULTS: The accuracy in describing a hand injury increased significantly
      for all anatomical structures except vascular lesions in patient records
      containing the hand injury chart compared with records without the chart. Using
      the chart saved one minute of time at the first aid station and the outpatient
      department. CONCLUSION: The use of a hand injury chart allowed a more accurate
      and uniform description. The computerized data could be easily used for
      scientific and audit purposes.

PMID- 9173302
TI  - [Endoscopic retroperitoneal adrenalectomy: a surgical improvement].
AB  - OBJECTIVE: Evaluation of endoscopic retroperitoneal adrenalectomy in patients
      with adrenal tumours less than 6 cm in diameter. DESIGN: Retrospective analysis.
      SETTING: University Hospital Rotterdam-Dijkzigt, Department of General Surgery,
      Rotterdam, the Netherlands. METHOD: Analysis of per- and postoperative data on 19
      patients subjected to endoscopic retroperitoneal adrenalectomy; 3 patients had
      bilateral surgery. RESULTS: Twenty adrenal tumours in 17 patients were
      successfully removed endoscopically. Conversion to lumbotomy was necessary in the
      two other cases. Median operative time was 85 min (range: 50-120). Median blood
      loss was 50 ml (10-400). Median postoperative hospital stay was 4 days (2-14).
      CONCLUSION: Endoscopic retroperitoneal adrenalectomy is associated with minimal
      morbidity and therefore valuable in patients with adrenal tumours smaller than 6
      cm in diameter.

PMID- 9173303
TI  - [Little HIV risk behavior in drug users during detention in Dutch
      penitentiaries].
AB  - OBJECTIVE: To assess levels of HIV risk behaviour in injecting drug users during
      and immediately following prison terms in the Netherlands. DESIGN: Descriptive.
      SETTING: Municipal Health Service, Amsterdam, the Netherlands. METHODS: Injecting
      drug users taking part in a follow-up study on HIV infection were interviewed on
      injecting drug use and vaginal and anal sexual contact during their last prison
      term in the 3 years preceding the interview and on injecting drug use in the week
      following release from prison. RESULTS: A prison term in the preceding 3 years
      was reported by 188 (41%) of 463 interviewed drug injectors. The mean age of the
      188 was 35.5 years: 146 (78%) were males, 63 (34%) had HIV antibodies, and the
      mean duration of latest prison term was 3.6 months. Some use of cannabis, heroin,
      or cocaine in prison was reported by 104 (55%), 69 (37%), and 38 (20%)
      respectively. Five injectors (3%) reported having injected in prison: in 4 cases
      once and in 1 case 3 times. No sharing of needles and syringes was reported.
      Vaginal or anal sex was reported by 2 (1%) of the men and none of the women.
      Relapse to drug injecting during the week following release from prison was
      reported by 78/186 (42%) participants, in most cases (34%) on the very day of
      release. CONCLUSION: Contrary to findings from other countries, low levels of HIV
      risk behaviour occur among imprisoned drug injectors in the Netherlands. Although
      noninjecting drug use in prison is common, drug injecting and the sharing of
      injecting equipment is rare. There appear to be no grounds for making clean
      needles and syringes available in Dutch prisons.

PMID- 9173304
TI  - [The body-packer syndrome].
AB  - In four patients, a woman of 35 and men of 27, 38, and 22 years old, body-packer
      syndrome was diagnosed. Body-packer syndrome is seen in people concealing drugs
      in special containers within the body; this may lead to rupture with acute
      intoxication or to ileus. The clinical presentation can be very deceptive. An
      abdominal X-ray often reveals the packages. If there are no symptoms treatment is
      with mild laxatives, acute intoxication requires immediate laparotomy. One of the
      four patients died, the others recovered. Legally (Dutch law), the physician best
      delivers the drug to the police as a lost object, without revealing the patient's
      identity.

PMID- 9173305
TI  - [A patient with rabies in The Netherlands].
AB  - A 49-year-old Moroccan man was admitted to hospital with chest pain and dyspnoea.
      The next day he had paresis of the left arm and because of respiratory arrest he
      was transferred to the intensive care unit. A fast-progressive neurological
      illness developed with flaccid tetraparesis, areflexia and a lowered level of
      consciousness. He died 11 days after admission. The strong clinical suspicion of
      rabies was confirmed by very high antibody titres in serum and CSF and by
      positive immunofluorescence in mice inoculated with the patient's CSF. This was
      the first case of rabies in the Netherlands since 1963.

PMID- 9173306
TI  - [Unity or mosaic? The development of considering the site-association of bodily
      functions to the brain].

PMID- 9173307
TI  - [Vegetative state].

PMID- 9173308
TI  - [Varicose veins: surgical removal (stripping) of the greater saphenous vein is
      preferable].

PMID- 9173309
TI  - [Atypical Parkinson syndrome].
AB  - Various clinico-pathological studies have shown that appr. 20% of patients with a
      clinical diagnosis of idiopathic Parkinson's disease (IPD) may have
      neuropathological evidence of alternative causes of parkinsonism. Most of these
      misdiagnosed "IPD" patients meet clinical criteria for either multiple system
      atrophy (MSA), or progressive supranuclear palsy (PSP), or corticobasal
      degeneration (CBD). A careful history and physical examination, as well as follow
      ups and selected investigations are essential for an accurate clinical diagnosis
      of these atypical parkinsonian syndromes. The following paper therefore provides
      a review of clinical features and diagnostic findings in MSA, PSP and CBD, in
      order to facilitate recognition of these patients.

PMID- 9173310
TI  - [Research possibilities of stroke databanks].
AB  - Stroke data banks (SDBS) have a growing importance in clinical research. They can
      be applied to a multitude of clinical issues. Hospital-based uni- or
      multicentered SDBS usually focus on syndromatology, pathogenesis and etiology. In
      contrast, classical epidemiological studies center upon complete case
      ascertainment within a geographically defined area (stroke registry). SDBS differ
      from conventional case series by their systematic collection of data within a
      specified time frame. Their main importance is the possibility to generate
      hypotheses quickly and cost-effectively. These hypotheses can serve as a basis
      for further prospective clinical studies. SDBS also show an important interaction
      with the design and conduct of clinical trials.

PMID- 9173311
TI  - [Treatment of acute stroke on the stroke unit. Initial experiences with an acute
      stroke unit in Germany].
AB  - We studied the effects of stroke unit care in an acute Neurology department on
      the outcome and the length of hospital stay in acute stroke patients. After an
      emergency evaluation on admission including CCT, ultrasound studies and ECG the
      patients were treated on a specialist stroke unit for an average 3.9 days. For 48
      +/- 24 h monitoring of blood pressure, ECG, pO2 and transcranial Doppler
      sonography was instituted. Stroke unit treatment reduced the length of hospital
      stay from an average 15.8 days in the time period before institution of the
      stroke unit to 12.9 days. This effect was especially marked in patients with
      acute occlusion of major intracranial arteries (before stroke unit treatment: n =
      33; hospital stay 22.5 days; after stroke unit treatment: n = 54; hospital stay
      13.9 days). Clinical deterioration in acute ischemic stroke was related to
      reduction of cerebral blood flow velocities due to blood pressure changes or
      space occupying effects. Monitoring on the stroke unit allowed immediate
      treatment of systemic hypotension, cerebral edema or cardiac arrhythmias.
      Transcranial Doppler sonography revealed HITS in 6/55 acute stroke patients
      without new clinical symptoms. Monitoring on the stroke unit improved the
      specific care for acute stroke patients. The length of hospital stay was reduced
      after stroke unit care.

PMID- 9173312
TI  - [Association of hypertension and diabetes mellitus with microangiopathic cerebral
      infarct patterns].
AB  - OBJECTIVE: To test the hypothesis of a positive association of hypertension and
      diabetes mellitus with cerebral small-vessel disease infarct patterns. METHODS:
      Using a prospective stroke database, the 152 patients with computertomographic
      signs of small-vessel disease (lacunes and/or leucoaraiosis)--including as a
      subgroup of 85 cases with multiple lacunes and/or leucoaraiosis-were compared
      with 106 patients featuring pial artery infarcts. Statistical analyses of the
      rates of hypertension and diabetes included univariate tests (odds ratios) and a
      logistic regression model comprising the additional variables
      hypercholesterolemia, cigarette smoking, carotid stenosis, atrial fibrillation,
      and left cardiac thrombus. RESULTS: Multivariate testing revealed a significant
      association of hypertension and diabetes with multiple lacunar infarcts and/or
      leucoaraiosis (hypertension: odds ratio 2.0; 95% confidence interval 1.04-3.7;
      diabetes: odds ratio 1.9; 95% confidence interval 1.01-3.8), whereas for the
      total group of patients with small-vessel disease lesions no such effect was
      found. Among the other tested variables, only atrial fibrillation/left cardiac
      thrombus showed a significant negative association (odds ratio 0.5; 95%
      confidence interval 0.2-0.9) with lacunes/leucoaraiosis. CONCLUSION: Independent
      of other risk factors and other possible causes of stroke, both hypertension and
      diabetes appear to be strong determinants of multiple lacunar infarcts and/or
      leucoaraiosis.

PMID- 9173313
TI  - [An unusual combination of carotid artery-cavernous sinus fistula and sinus
      thrombosis. Successful therapy with anticoagulation].
AB  - Dural carotid cavernous fistulas (DCCF) can be associated with venous thrombosis.
      We report on a rare case of a patient who developed a venous infarct, which was
      diagnosed on CT and MRI. The DCCF predominantly drained through a frontobasal
      cortical vein into the superior sagittal sinus. The shunt volume was small and
      was therefore thought not to be sufficient to explain the massive ocular signs,
      such as severe exophthalmus and reduction of visual acuity. We therefore
      postulated a venous congestion owing to a secondary spontaneous venous thrombosis
      of the draining venous pathways to be responsible for the ocular signs. Under
      anticoagulative medication, the patient's signs and symptoms improved gradually.
      Control angiography after 3 months showed that the DCCF had disappeared. In the
      presence of DCCF, anticoagulation should always be considered when a venous
      thrombosis is suspected.

PMID- 9173314
TI  - [Lateral cranial dural fistula. Detection with Doppler and duplex ultrasound].
AB  - Cranial dural fistulae are rare; when they occur, it is usually difficult to
      detect them at an early stage. With a view to the question of possible progress
      in diagnosis we now report on seven patients with lateral dural fistulae fed by
      branches of the external carotid artery. The examination was carried out before
      selective arteriography using cw-Doppler sonography and colour coded duplex
      sonography in combination. Sonographic criteria for detection of hyperperfusion
      take account of flow velocity as well as pulsatility. In all cases hyperperfusion
      of the external carotid artery was detected. In most of these cases pathologic
      findings were also observed at the occipital artery, and more rarely in the
      contralateral external carotid artery or the ipsilateral vertebral artery, in
      addition. A possible source of error arising from confusion of blood vessels was
      present with the cw-Doppler sonography, but not for colour coded duplex
      sonography. Therefore, cranial dural fistulae characterized by a high shunt
      volume can be diagnosed correctly by indirect Doppler sonographic criteria using
      cw-Doppler and duplex sonography. Direct visualization of the fistula and its
      nidus requires additional selective arteriography, in the course of which
      endovascular embolization may be performed.

PMID- 9173315
TI  - [Sympathetic reflex dystrophy in circumscribed stenosis of the abdominal aorta.
      Case report and discussion of pathophysiologic principles].
AB  - Reflex sympathetic dystrophy (RSD) is a pain syndrome characterized by
      somatosensory and motor disturbances, as well as by autonomic and trophic
      changes. The term is used in a descriptive sense and does not imply specific
      mechanisms of pathogenesis. We report on a patient who fulfilled the clinical
      criteria of RSD and who also displayed increasing impairment of peripheral blood
      supply. Angiography revealed a circumscribed stenosis of the abdominal aorta
      adjacent to the bifurcation. Disturbances in peripheral circulation as a
      potential cause of RSD are discussed.

PMID- 9173316
TI  - [Liver transplantation in familial amyloid polyneuropathy].

PMID- 9173317
TI  - [Indications and value of thymectomy in myasthenia gravis].
AB  - The therapeutic impact of thymectomy on the clinical course of myasthenia gravis
      is still a matter of debate. Issues in this discussion that are clinically
      relevant are reviewed. While the surgical procedure is accepted for thymomas its
      performance is controversial in cases with no thymomatous tissue. Outcome studies
      show a weak correlation between clinical course and thymus histology, but there
      is some doubt about the maximum age for thymectomy and about the therapeutic
      regimen following surgery. Retrospective studies show that thymectomy has a
      beneficial influence on the natural course of myasthenia. This positive effect is
      enhanced by appropriate immunosuppressive therapy together with
      anticholinesterase inhibitor substitution. Unfortunately, the different forms of
      myasthenia do not all respond in the same manner. Studies have shown that thymoma
      associated myasthenia is more difficult to control than non-thymoma-associated
      myasthenic states. In both groups some patients go into remission after
      thymectomy alone, and the majority of patients with the institution of additional
      immunosuppression. In clinically mild cases thymectomy should not immediately be
      followed by immunosuppression. This will help to identify those patients
      responding with remission to thymectomy alone. Mostly these are young women with
      a hyperplastic thymus. Overall, thymectomy is beneficial and should be considered
      in all patients with generalized myasthenia who are still under 60 years of age.

PMID- 9173318
TI  - [Multiple sclerosis. New therapeutic strategies in the experimental stage].
AB  - Extensive research in the field of multiple sclerosis (MS) has lead to a
      preliminary pathogenetic concept without solving the etiopathogenesis. According
      to animal experiments and human in vitro studies MS is a T cell-mediated
      autoimmune disease. Experimental therapeutical strategies are aiming at the
      inhibition of T cell activation, transmigration through the blood brain barrier
      and local inflammation and demyelination. Several substances are already being
      tested in clinical studies with magnetic resonance imaging as a tool to quantify
      inflammatory lesions and to shorten the study course. This review will give a
      summary about actual experimental therapies resulting from the current
      pathogenetic concept.

PMID- 9173319
TI  - [A plant extract with proven antidepressive effect].

PMID- 9173320
TI  - [Chemical composition of Hypericum perforatum and its effects].

PMID- 9173321
TI  - [Antidepressive effectiveness and good tolerance].

PMID- 9173322
TI  - [Hypericum perforatum in psychiatric practice].

PMID- 9173323
TI  - [The blood-brain barrier. II. Pathology: brain tumors, brain edema, hypertension,
      epilepsy].
AB  - In the first part of the publication the authors presented the blood-brain (BBB)
      under physiological conditions. The second part includes the current opinions
      concerning BBB during various disorders of the central nervous system (CNS) and
      hypertension. The imbalance of BBB is often not only a consequence of a
      pathologic status, but can be also cause of it. On the other hand BBB influences
      the therapy of many illnesses by restricting the penetration of drugs to the CNS.

PMID- 9173324
TI  - [The role of sodium serum level disturbances in the development of central
      pontine myelinolysis].
AB  - Central pontine myelinolysis now is believed to be a polyetiological syndrome.
      Our case was diagnosed clinically due to typical neurological symptoms occurred
      in the course of the treatment hyponatraemia and hypokaliaemia. Forty six years
      old woman an alcohol abuser, with liver dysfunction was admitted to neurological
      department in the first grand mall attack. She was tetraplegic, with signs of
      alcoholic polyneuropathy simultaneously hyponatraemia and hypokaliaemia were
      observed. Two weeks after normalization of electrolytic alterations, symptoms of
      brain stem lesion appeared. Based on MRI and clinical symptoms the diagnosis of
      central pontine myelinolysis was suggested and proved on autopsy. Electrolytic
      disturbances and treatment are discussed.

PMID- 9173325
TI  - [Primary brain lymphoma: diagnostic problems].
AB  - Diagnostic difficulties in a patient with primary malignant lymphoma of the brain
      are presented. Computerized tomography scans disclosed, at the beginning, a large
      mass located in the frontocallosal region, and 15 months later another focus in
      the cerebellum. Differential diagnostic considerations based on CT and NMR
      pictures, included infectious diseases, demyelinating diseases also metastatic
      tumours. The patient was successfully treated surgically, and had than
      radiotherapy.

PMID- 9173326
TI  - [Hyperkalemic periodic paralysis or congenital paramyotonia: an attempt of
      treatment with phenytoin].
AB  - Authors describe 2 patients with hyperkalemic period paralysis where positive
      therapeutic effect was achieved after treatment with phenytoin. They compare the
      features of paramyotonia congenital with hyperkalemic period paralysis and they
      think that they are the same disease with different clinical signs.

PMID- 9173327
TI  - [Superior sagittal sinus thrombosis: a case report].

PMID- 9173328
TI  - [Brain tumor and imminent premature labor: a case report].
AB  - A pregnant woman with cerebral tumour of right hemisphere is reported. In the
      30th week of pregnancy intracranial pressure was increased and imminent premature
      delivery were diagnosed. The patient was operated on for cerebral tumour and
      immediately after this cesarean section was performed. We conclude that in this
      case neurosurgical operation followed by cesarean section saved the life of the
      mother and child.

PMID- 9173329
TI  - [Right eye blindness as the predominating clinical sign in a patient with aortic
      arch syndrome: a case report].
AB  - A case is described of pulseless disease in 43 years old man with right-sided
      blindness as the main clinical sign. The brain was supplied with blood via the
      left vertebral artery. The cerebral circulation was additionally diminished by
      coexisting subclavian steal-syndrome with reversal of blood flow in the right
      vertebral artery.

PMID- 9173330
TI  - [Ultrasonographic study of cerebral blood flow in hemorrhage strokes].
AB  - The cerebral blood flow was studied by means of transcranial ultrasonographic
      recording in hemorrhagic strokes. In acute phase of stroke the diastolic and mean
      velocity was slowed down and the pulsation index PI and resistance index RI were
      increased. Following of the changes of these indices may be of prognostic
      importance.

PMID- 9173331
TI  - [Oligosymptomatic presentation of tuberous sclerosis in two pedigrees].
AB  - The authors describe clinical course of tuberous sclerosis in seven family
      members from two pedigrees. They stress the importance of careful medical
      anamnesis and skin examination in family members of persons affected with
      tuberous sclerosis. It is pointed out that in contrast to widespread stereotype
      of a patient with tuberous sclerosis-a person with epilepsy, mental retardation
      and multiple skin and organ involvement, much more common than it was previously
      thought, the course of the disease may be oligosymptomatic and the affected
      person may properly function in society. All 7 affected persons presented in the
      paper were mentally normal and only two of them suffered from epilepsy.

PMID- 9173333
TI  - [Analysis of peak 1st latency in brainstem auditory evoked potentials in newborns
      aged 1 to 14 days].
AB  - BAEPs examinations performed in healthy newborns aged up to 14 days of life
      revealed that in the youngest group (up to 4 days of life) the percentage of the
      results with delayed peak I latency was relatively high -57.8%. In the further
      age group (5-7 days of life) the number of the abnormal results decreased
      considerably down to 14.1%.

PMID- 9173332
TI  - [Visual system in the light of the study of evoked potentials after stimulation
      by pattern stimuli in healthy subjects].
AB  - In 65 healthy subjects aged 18-70 the characteristics of VEPs elicited with two
      kind of "pattern reversal" stimulus, checkerboard and gratings, in 13 various
      configurations were tested. In the recordings the latency and amplitude of peaks
      P1, N1, P100 and N2, and the difference between maximum and minimum amplitude and
      correlation coefficient for the cerebral hemispheres were analysed. It was found
      that checkerboard and gratings elicited in the both hemispheres the responses of
      comparable latencies and their amplitudes were consequently greater over the left
      hemisphere. Analyses of the correlation between VEPs and gender showed no
      influence on latencies and the occurrence of greater amplitudes in females and
      lower correlation coefficients in males. Differences were noted between
      potentials evoked by monocular and binocular stimulation, and for the responses
      elicited with the patterns of checkerboard and gratings, which reflects the
      activation of two separate channels of the visual system. It was also shown that
      the characteristics of VEPs obtained using for stimulation the fractionated
      visual field (checkerboard in the individual hemi-fields and quadrants) was
      consistent with the topography of visual pathways and retinotopic organisation of
      the striate cortex, which would suggest a location of the main generator of VEPs
      in Brodmann's area 17.

PMID- 9173334
TI  - [Effect of phenytoin and carbamazepine on evoked potentials in patients with
      newly diagnosed epilepsy. Part I. Visual evoked potentials].
AB  - Pattern-reversal visual evoked potentials (VEPs) were recorded in 64 patients
      with newly diagnosed epilepsy. Before starting medication the patients with
      partial and primary generalized epilepsy, had prolonged latencies of the VEPs
      component P100, as compared with controls. VEPs were repeated after 3 months in
      43 patients with focal epilepsy, during carbamazepine (22 cases) or phenytoin (21
      cases) treatment. The plasma concentration of the drugs were within therapeutic
      levels. Carbamazepine but not phenytoin, was associated with prolongation of the
      P100 peak latency and induced increase of its amplitude, as compared with the
      baseline condition. The VEPs abnormality was most pronounced in patients whose
      seizures were poorly controlled. We conclude, that administration of
      carbamazepine or phenytoin, at therapeutic serum level, have minimal effect on
      the VEPs.

PMID- 9173335
TI  - [Effect of phenytoin and carbamazepine on evoked potentials in patients with
      newly diagnosed epilepsy. Part II. Brainstem auditory evoked potentials].
AB  - Brainstem auditory evoked potentials (BAEPs) were studied in 64 untreated
      epileptics with partial (58) and primary generalized seizures (6). Patients were
      randomized to have either phenytoin (PHT) or carbamazepine (CBZ) monotherapy.
      Follow-up recordings were made 3 months after PHT (21) or CBZ (22) monotherapy in
      43 patients with partial seizures. Before treatment epileptic patients and
      controls did not differ in BAEPs results. All patients had therapeutic PHT or CBZ
      levels. PHT prolonged I-III and I-V interpeak latencies (IPL), and central
      conduction time (I-V) changes were correlated with the patients age. CBZ
      increased the latency of wave I and the central conduction time. The prolongation
      of I-III IPL was significant only for the group with partial secondarily
      generalized seizures and the III-V for the group with partial seizures without
      generalization. These results suggest similar effects of CBZ and PHT on BAEPs
      within serum therapeutic range.

PMID- 9173336
TI  - [Clinical assessment of calvarial reconstruction with autogenic bone graft or
      implants of acrylate and polypropylene-polyester knitted fabric].
AB  - During the period between 1972-1992 32 patients with calvarial bone defects were
      treated by 35 reconstructions. The paper presents early and late results of
      various methods of reconstructions. Very good late results were achieved in all 5
      patients in whom the defects were reconstructed with autogenic split cranial bone
      graft. There were equally good results in 19 from 22 patients in whom acrylic and
      propylene-polyester implants were applied. Total resorption of autogenic split
      iliac and split rib bone graft were observed in all 5 patients in whom skull
      defects were filled with this tissue.

PMID- 9173337
TI  - [Clinical significance of the pharmacogenetics in psychiatric and neurological
      syndromes].
AB  - The aim of the paper was the presentation of the newest results of studies in
      pharmacogenetics of psychiatric and neurological syndromes. It was especially
      emphasized an important role of pharmacogenetics in safe pharmacotherapy of
      psychiatric and neurological syndromes.

PMID- 9173339
TI  - [Estrogen-progestin contraception and biohumoral response of new markers of the
      atheroma risk. Behavior of lipoprotein(a) and apolipoproteins A and B].
AB  - A homogeneous group of 45 patients, aged between 19 and 37 years was considered
      in relationship to metabolic response during oral contraceptive use. A free
      endocrinological-metabolic pathology control group, formed by 30 patients, aged
      between 22 and 35, who were not treated with any therapy in the six months
      before, was also considered. We also considered any other factors like smoking,
      height, and weight in all women of our study. Study-trial was comprehensive of a
      12 months follow-up, with some periods of study at 0, +6, +12 months. Metabolic
      responses of lipoprotein(a) and apolipoprotein A and B during the different
      follow-up steps were determined. Total and fractionated cholesterol and
      triglycerides were also determined. Positive correlations were shown between
      Lipo(a) and Apo B and also between total cholesterol and LDL. Negative
      correlations were shown between Lipo(a) vs HDL and Apo A. Lipoprotein(a) was
      determined by the ELISA technique and turbidimetric technique. The aim of our
      study was to verify the importance of the new markers of atheroma risk; even if
      the oral estrogen-progestin contraception little interferes with this biohumoral
      marker synthesis, it improves atheroma risk protection through the lipidic
      metabolism complexity.

PMID- 9173338
TI  - [Postmenopausal osteoporosis: therapeutic approaches].
AB  - The preventive and therapeutical measures to be implemented the post-menopausal
      osteoporosis are varied, although there is no clear, single protocol of
      intervention. ESTROGENS AND PROGESTOGENS: It si verify that the administration of
      estrogens and/or progestogens prevents bone loss with an action on mineral
      components of bone and on collagenic metabolism. BIPHOSPONATES: Operate
      inhibiting mineralization and, particularly, bone reabsorption. At present its
      use, in low dosages, is reserved to "fast bone loser" patients. CALCITONIN: It
      increases bone mass and significantly reduces the frequency of fractures in
      comparison with only calcium, but its use is limited by high costs. IPRIFLAVONE:
      Anti-reabsorption effects has on bone and stimulates osteoblastic activity;
      besides, it seems to developed the effect of estrogens on the bone. FLUORIDES:
      Fluorides also operate on both components of bone turnover, with a most important
      action on bone formation. An interesting approach is the association of low doses
      of monofluorophosphate with calcium. However, further confirmation of the
      "quality" of neoformed bone is necessary. CALCIUM: Calcium supplementation is
      obligatory where the alimentary supply of calcium is lower then 1 g/die or where
      an osteomalacic component coexists; only dosages higher than 15 g/die can
      produce/pharmacological effects on bone turnover. CALCITRIOL: The use is still
      disputed. The calcitriol-calcium association seems convincing haveved. ORG: OD
      14. The efficacy of this synthetic steroid to prevent bone loss is probably
      superimposable on the efficacy of classic estrogen therapy.

PMID- 9173340
TI  - [Conservative management of ectopic pregnancy].
AB  - BACKGROUND: The aim of this retrospective study was to analyze the safety and
      efficacy of the conservative approach in the management of ectopic pregnancy.
      METHODS: Thirty-five women with a tubal ectopic pregnancy, from 1990 to 1995,
      were subdivided into 2 treatment groups. Inclusion criteria were the following:
      tubal diameter < 3 cm, free fluid < 100 ml, no embryo heart activity,
      haemodynamic stability. Desire of future fertility and informed consent were
      requested. Eighteen women were treated with a single intramuscular injection of
      methotrexate, whereas in 17 cases expectant management was adopted. RESULTS: In
      the first group 2 cases required surgical treatment (resolution rate = 89%). In
      the second group no surgery was needed and spontaneous resolution was achieved in
      all cases (100%). In both groups the average resolution time was about 17 days.
      Serum hCG-beta levels were monitored daily until resolution. The initial hCG-beta
      value and its following trend seem to be the most important prognostic factors.
      CONCLUSIONS: More studies are indeed needed to establish the effect of
      conservative management on fertility after ectopic pregnancy.

PMID- 9173341
TI  - [Metabolic compensation and malformations in pregnancy complicated by diabetes].
AB  - Congenital malformations are considered the more frequent perinatal complications
      affecting offsprings of diabetic mothers; they represent the main cause of
      mortality of these neonates. Since diabetes is strictly controlled, the incidence
      and the seriousness of its complications are reduced from 8-10% to 2-3%. In this
      study we followed 56 pregnancies complicated by diabetes. There were 3 case of
      malformations. We correlate these with the metabolic maternal balance and with
      the HbA1c values. We could confirm the relationship between malformation and
      metabolic imbalance and also the absence of fetal malformations in women with
      metabolic compensation since the beginning of the pregnancy.

PMID- 9173342
TI  - [Echographic follow-up after laparoscopic enucleation of endometrioma].
AB  - The authors report their experience of the ultrasonic follow-up of endometriomas
      after laparoscopic enucleation. Fifty women with sixty-six endometriomas were
      treated: the average diameter of the endometriomas is 4.2 cm. The clinical and
      ultrasonic follow-up of 21 months shows: -the disappearance of the ovary's
      solution of continuity after laparoscopic enucleation of the endometriomas; -the
      persistence of deep endometriomas; -the presence of residual fragments of the
      endometrioma's capsule; -the appearance of relapsing endometriomas.

PMID- 9173343
TI  - [Perinatal outcomes of newborn infants of mothers over 40 years old. A case
      control study].
AB  - The changing life patterns for women in current society are accompanied by a
      postponement of pregnancy in advanced reproductive age. The aim of our study was
      to compare perinatal outcome among 314 newborns from women > or = 40 years old
      with 6.683 controls from mothers 20-29-year-old who delivered at our Division
      between 1983 and 1993. For each analyzed variable (birth weight, gestational age,
      congenital malformations, still-births, neonatal mortality and morbidity) the
      odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the
      group of women > or = 40 years old. The incidence of nulliparas in the older age
      group was 13.5%. The cesarean section rate was higher in the mature mothers than
      in their younger controls (52.1% vs 34.7%). The more frequent prenatal genetic
      management in women past the age of 35 years may be the reason for the reduced
      overall frequency of still-births and malformations in the group > or = 40 years.
      Preterm delivery was observed more frequently in the older mothers compared with
      controls (18.5% vs 11.7%). The frequency of LBW and VLBW was higher, but not
      significant, in the cases than in the controls. Newborns from older mothers had a
      significant increase of macrosomia (8% vs 4.8%) and a twice increase of mortality
      (3.2% vs 1.6%) and morbidity (20.4% vs 11.4%). These data suggest to improve the
      perinatal care of women > or = 40 years old.

PMID- 9173344
TI  - [Behavioral states. An in utero study].
AB  - OBJECTIVE: This study aims to show how a single linear transducer and different
      state variables can be used to enable accurate identification of behavioural
      states. DESIGN: Prospective observation study. SETTING: Clinic of Obstetrics and
      Gynaecology III at the "Federico II" University of Naples. SUBJECTS: Fifteen
      fetuses of women hospitalized in the Clinic of Gynaecology at the "Federico II"
      University of Naples at the end of a full-term, uncomplicated, single pregnancy
      with a reliably dated last menstruation. METHODS: Ultrasound observation,
      registration and data processing of various fetal activities in the uterus mouth
      movements (sucking), other mouth movements, eye movements, gross body movements.
      RESULTS: The fetal activities identified correspond exactly to the criteria
      established for the definition of state variables. An examination of the data
      thus obtained shows an inverse correlation between mouth movements and the other
      activities, and a direct correlation between the other three variables we
      considered. CONCLUSIONS: The results obtained in our study show that this method
      can be profitably used to identify the behavioural states, in full-term,
      uncomplicated pregnancies.

PMID- 9173345
TI  - [Incidence of lunar position in the distribution of deliveries. A statistical
      analysis].
AB  - OBJECTIVE: To point out the influence of the lunar position on the distribution
      of deliveries. METHODS: We examined all the full-term spontaneous deliveries that
      occurred at the Civil Hospital in Fano (March) throughout 24 synodic months in a
      2-year period (1993-1994). In order to perform the statistical analysis, each
      delivery was considered as a single measure. We used techniques of circular
      statistics to execute data analysis. RESULTS: A significant relationship between
      lunar position and distribution of deliveries was pointed out in multigravidae
      (in detail, the deliveries resulted clustered around the full moon phase). On the
      contrary, no significant relation was observed in primigravidae. CONCLUSIONS: The
      observed results evidence a significant influence of the position of the moon on
      the distribution of deliveries, especially in multigravidae.

PMID- 9173347
TI  - Seven steps for preventing lethal chemotherapy overdoses.

PMID- 9173346
TI  - [Embryo-fetal ultrasonographic diagnosis in the early pregnancy using
      transvaginal echography].
AB  - The diagnostic capability of high resolution transvaginal sonography in early
      pregnancy is described. Transvaginal sonography allows for the visualisation of
      some fetal organs and structures one to four weeks earlier than transabdominal
      ultrasound thus permitting evaluation of several embryofetal parameters early in
      pregnancy. This technique permits formulation of fetal measurement charts and
      detection of embryo-fetal malformations during the initial stages of pregnancy.
      Knowledge of the transvaginal sonographic appearance of embryonal and fetal
      biometric and structural anatomy enables us to determine the appearance of the
      normal fetus. Transvaginal scan may be employed as a screening tool for the
      identification of fetal anomalies in early stages of pregnancy. An increasing
      number of case reports and documented records of cases of malformations and
      anomalies diagnosed during the first trimester of pregnancy using this technique
      have been reported in the literature. The most frequent embryo-fetal
      malformations and anomalies detected at transvaginal scan and the earliest
      gestational age of diagnosis are described. At present a limited number of
      anomalies can be diagnosed because only a part of the potentially recognizable
      anomalies have been described using this technique. The importance of this new
      imaging technique as well as the necessity of a through knowledge of embryology
      are evident. Transvaginal sonography allows for biometric evaluation, for a
      clearer visualization of embryo-fetal morphology and for detection of several
      malformations and anomalies during early pregnancy.

PMID- 9173348
TI  - [The morphogenetic reactions of the ectoderm in the early gastrula of the clawed
      toad to mechanical stretching].
AB  - The ventral ectoderm explants of the Xenopus laevis early gastrula were stretched
      on an elastic substrate 1.5- to twofold for 30 min, then fixed in the stretched
      state and incubated for up to 6 h. The stretching of explants generated their two
      phase active reaction, which was estimated using the criterion of eccentricity of
      cells and whole explants developed in this study. At the first phase, during the
      external force application, the explant cells were elongated towards its
      stretching to a markedly greater extent than the whole explant: eccentricity of
      the whole cells exceeded that of the whole explants. Cell processes elongated in
      the same direction appeared, cell contacts and apical cytoskeleton structures
      developed, and mechanical tensions increased. At the second phase, within 5 h
      after the stretching, the shape of individual cells, rather than the whole
      explant, returned to the initial one (approximately isotropic), mechanical
      tensions decreased, and visible morphogenesis of the explant proceeded: it
      acquired a complex shape with longitudinal groove and polar thickenings. We
      conclude that intercalary movements of the cells are present at the second phase
      of the active explant reaction and morphogenesis is realized at the phase of
      relaxation of mechanical tensions.

PMID- 9173349
TI  - [The formation and regulation of the lactotrophic function of the hypophysis in
      the prenatal period of rat development. I. Prolactin secretion by the hypophysis
      and the role of dopamine in this process].
AB  - Using radioimmunologic assay, we have studied the content of prolactin in the
      pituitary and its release into general circulation in 18-, 20-, and 22-day-old
      rat fetuses under normal conditions and after pharmacological block of dopamine
      receptors. Prolactin was found in the pituitaries of the fetuses from day 5 and
      in blood serum, from day 18; its levels were progressively increasing up to the
      end of prenatal development. Administration of haloperidol, an inhibitor of
      dopamine D2 receptors, to pregnant female increased the level of prolactin in
      fetus plasma from day 20 and diminished its content in the pituitary gland from
      day 22. These data provide evidence for secretion of prolactin by the pituitary
      and sensitivity of lactotrophs to dopamine during prenatal development.

PMID- 9173350
TI  - [The formation and regulation of the lactotrophic function of the hypophysis in
      the prenatal period of rat development. II. Dopamine inhibitory control of
      prolactin secretion].
AB  - Using the technique of radioimmunoassay, we studied the secretion of prolactin
      and its control by dopaminergic system in 22-day-old rat fetuses under normal
      conditions and after pharmacological inhibition of dopamine receptors. In order
      to elucidate the origin of prolactin and dopamine participating in this process,
      we used decapitation and encephalectomy of fetuses in utero. Decapitation of
      fetuses did not result in any changes of baseline prolactin secretion into blood
      in males and insignificantly decreased it in females as compared with nonoperated
      controls. We conclude that prolactin detected in blood plasma of nonoperated
      fetuses does not originate in the pituitary, and any prolactin synthesized in the
      pituitary is not secreted into blood. Inhibition of dopamine receptors in
      decapitated fetuses did not result in any changes of prolactin level in blood.
      This provided evidence that in nonoperated fetuses, it is pituitary prolactin
      which is secreted in response to haloperidol, while the secretion of nonpituitary
      prolactin is not controlled by dopamine. Encephalectomy increased prolactin level
      in plasma and resulted in a drastic decrease of its level in the pituitary. The
      block of dopamine receptors did not affect the level of prolactin in blood plasma
      or pituitary of encephalectomized fetuses. We conclude that the inhibitory
      dopaminergic control of prolactin secretion by the pituitary during the prenatal
      period is accomplished just as in adult animals by dopaminergic neurons of
      hypothalamus.

PMID- 9173351
TI  - [The positive effect of pretreatment with serotonin and gangliosides on the
      development of early mouse embryos after cryopreservation].
AB  - We have demonstrated that viability of preimplantation mouse embryos F1 (C57B1/6
      x CBA) after cryoconservation at the stage of four blastomeres improves after
      pretreatment with serotonin (5 HT, 5 microM) or total gangliosides of bovine
      brain gangliosides (TG, 3 microM) added to the cultivation medium. After thawing,
      64% of embryos preincubated with total brain gangliosides and 49% of embryos
      preincubated with serotonin developed to the stage of blastocyst during the
      cultivation in vitro; in the control, no more than 25% of embryos reaches this
      stage, and all these embryos were abnormal. Possible mechanisms of protective
      action of these compounds is discussed. We conclude that mouse embryos subjected
      to freezing-thawing procedure can be used to examine the role of serotonin and
      gangliosides in the regulatory processes of mammalian preimplantation
      development.

PMID- 9173352
TI  - [Differential gene expression during the reparative regeneration of differing
      polarities in planarians].
AB  - We identified two new genes (scarf and collar) of planarians using subtracting
      hybridization. mR-NAs of these genes are distributed in different ways in
      regeneration blastemas of different polarity. Zone-specific expression of these
      genes in non-regenerating planarians has been demonstrated. The level of
      expression of the identified genes in the head regeneration buds of the first
      third days of regeneration was lower than that in the corresponding intact
      tissues and tail regeneration buds.

PMID- 9173353
TI  - [Ultroser-G and 5-azacytidine prolong the development of parthenogenetic mouse
      embryos].
AB  - We studied the effects of Ultroser-G, a substitute of embryonal serum, and 5
      azacytidine, a DNA-demethylating compound, on development of diploid
      parthenogenetic embryos of the mouse inbred strain CBA and hybrids (CBA x
      C57BL/6)F1. Addition of Ultroser-G to the nutrient medium for in vitro
      cultivation of the embryos to a final concentration of 0.5% leads after their
      transplantation into the uterus of pseudopregnant females to development of
      parthenogenetic postimplantation embryos to a stage of 30-33 somites with the
      buds of fore- and hindlimbs. Additional introduction of 5-azacytidine at 0.24
      mg/kg to the females on day 8 of gestation prolonged development of some
      parthenogenetic embryos treated with Ultroser-G during the preimplantation period
      to the stage of 45 somites. The control embryos developed to the stage of 25
      somites. The mechanism of genomic imprinting and influence of the embryonal serum
      components and demethylating compounds on viability of the parthenogenetic
      embryos are discussed.

PMID- 9173354
TI  - [The postnatal development of the hemato-C-cellular system in the thyroid of rats
      sympathectomized with guanethidine].
AB  - We used ultrastructural morphometry to examine submicroscopical organization of
      spatial contacts between the C-cells and perifollicular hemocapillaries in the
      thyroid gland of 2-, 4-, 12-, 26-, and 52-week-old rats desympathized with
      guanetidine. We found that desympathization does not affect typology of
      ultrastructural elements of the hemato-C-cellular complex, and predominant
      coupling of the vascular pole of the C-cell with peripheral zone of
      endotheliocyte highly effective in terms of transport. Postnatal changes of
      certain parameters of the hemato-C-cellular system, however, undergo some
      statistically significant changes. Under experimental conditions, we observed the
      formation of hemato-C-cellular contacts simultaneously involving two C-cells.

PMID- 9173355
TI  - [The centenary of the birth of Grigorii Konstantinovich Khrushchov (1897-1962)].

PMID- 9173356
TI  - [A quantitative analysis of the development of the auditory centers of the
      medulla oblongata in the hen].
AB  - Development of three auditory nuclei in medulla oblongata was studied in the
      chicken (Gallus gallus). Quantitative description of the volume growth of the
      magnocellular nucleus neurons and linear growth of the auditory nuclei is given
      from the formation of differentiated neuroblasts (Day 9 of embryogenesis) until
      the 180th day of postembryonic development. Growth of the embryos was described
      according to the Bertalanffy's model. Growth of the neurons proceeded at the
      highest rate at the rostral level of magnocellular nucleus (mN = 1.204
      microns/day) and the lowest rate of the caudal level (mN = 1.045 microns/day).
      The curve of linear growth of the auditory nuclei is similar with the growth
      curve of the neurons and follows the Bertalanffy's equations. The magnocellular
      nucleus is characterized by the fastest growth (mN = 75.6 microns/day) and the
      angular nucleus by the slowest growth (mN = 52.0 microns/day). The growth of the
      neurons and auditory nuclei decreases before hatching.

PMID- 9173357
TI  - Parasites of South African wildlife. XIV. Helminths of nyalas (Tragelaphus
      angasii) in the Mkuzi Game Reserve, KwaZulu-Natal.
AB  - The helminthis of 58 nyalas (Tragelaphus angasil) culled in the Mkuzi Game
      Reserve, KwaZulu-Natal, during March 1991, and six culled during March 1994, were
      collected, identified and counted. Of these, an as yet undescribed
      Camelostrongylus sp., Cooperia hungl. an Onchocerca sp., Strongyloides papillosus
      and Moniezia benedeni are new parasite records. The individual nematode burdens
      of the antelope examined during March 1991 varied from one to 2327, and the total
      mean adult gastro-intestinal-nematode burden was 586. Those examined during March
      1994 had burdens that varied from 322 to 1778, with a mean of 854. The two
      Camelostrongylus spp. were the most prevalent nematodes in the nyalas culled
      during 1991, while the trematode Cotylophoron jacksoni was most prevalent in
      those culled during 1994. The most numerous nematode in nyala calves during 1991
      was a Cooperia rotundispiculum race, while the two Camelstrongylus 5pp. were most
      numerous in the adult and sub-adult nyalas from both surveys. No clear trends
      between rainfall and nematode burdens were evident, or was there any correlation
      between faecal nematode egg counts and nematode burdens. Contrary to what was
      observed in an earlier survey, female nyalas had larger nematode burdens than the
      males.

PMID- 9173358
TI  - Seasonal dynamics of the Karoo paralysis tick (Ixodes rubicundus): a comparative
      study on Merino and Dorper sheep.
AB  - Karoo paralysis in South Africa is induced in livestock by feeding female Ixodes
      rubicundus ticks when infestation densities on hosts exceed certain critical
      levels. It has been shown previously that Angora goats are at a higher risk of
      being paralysed than Merino sheep, and such differences have been related to
      differences in feeding behaviour and spatial distribution of the two small-stock
      breeds. We hypothesized that differences in infestation densities with Karoo
      paralysis ticks would also occur between Merino and Dorper sheep breeds. A study
      was conducted under natural conditions in the south-western Free State, to
      compare infestation burdens of the two sheep breeds and also to investigate
      seasonal patterns and annual variations in variations in terms of rainfall and
      temperature. Ten animals of each breed ran free in an area with a known history
      of Karoo paralysis and were examined on an approximately fortnightly basis, from
      March 1992 to December 1995, to determine tick abundance. Differences between the
      two breeds were significant (P < 0.05) during 1992 and 1993, but not during 1994.
      During the first two years, peak abundance of ticks was reached earlier in Dorper
      than in Merino sheep, and it also reached higher levels in Dorper than in Merino
      sheep (mean = 17.9 and 7.3, respectively). In 1993, two Dorper, but no Merino
      sheep, were paralysed. Dorper sheep are clearly at a higher risk of being
      paralysed than are Merino sheep, and as such, they can serve as indicators of
      adult tick activity and hence of the time to commence prophylactic treatment.
      Differences between the two breeds are probably related to differences in grazing
      patterns. Marked variation in abundance and the time of onset of peak activity of
      I. rubicundus occurred over the years. Tick numbers were high in 1993 and 1995,
      but very low in 1992. In 1993, peak activity occurred earlier (April) than during
      the other years (June or July). These differences are related to differences in
      prevailing environmental conditions that influence tick activity in a complex
      manner. Heightened humidity and lower temperatures during the early stages of
      seasonal activity of the tick (April or May), normally result in peak abundance
      of ticks on hosts at that time.

PMID- 9173359
TI  - Experimentally induced chronic copper toxicity in cattle.
AB  - Eight Bonsmara bulls and eight Bonsmara heifers, having masses of between 210 and
      266 kg when selected, were randomly allocated to four groups, each comprising two
      bulls and two heifers. Group 1 received 0.6 mg of copper (Cu)/kg of body mass per
      day (bm/d), group 2, 10 mg of Cu/kg of bm/d and group 3, 20 mg of Cu/kg of bm/d
      as a copper sulphate solution, given orally, 5 d a week over 745 d. Group 4 was
      the control group. One bull from group 3 was euthanased on day 679 of the trial,
      a heifer from group 3 and a bull from group 2, on day 695 of the trial, and a
      heifer from group 2, on day 731 of the trial, after they had shown clinical
      signs. During the course of the trial, clinical signs, serum gamma
      glutamyltransferase and aspartate aminotransferase activity, blood urea nitrogen,
      and plasma copper, zinc and iron concentrations were monitored. Live mass was
      recorded weekly to determine any effect on mass gain. The liver and kidney
      copper, zinc, iron and managanese concentrations at the time of death or
      slaughter are given. From the results it was concluded that subclinical damage to
      the liver and eventual copper toxicity can occur when cattle are continually
      exposed to oral doses > or = 12 mg of Cu/kg of bm/d. It was also concluded that
      cattle can probably tolerate oral doses of < or = 0.6 mg of Cu/kg of bm/d for an
      indefinite period, provided there are no other sources of copper, such as may
      occur with air-pollution, or provided no other adverse mineral interactions
      occur, such as may occur with molybdenum deficiency.

PMID- 9173360
TI  - Control of pest blackflies (Diptera:Simuliidae) along the Orange River, South
      Africa: 1990-1995.
AB  - The efficacy of Bacillus thuringiensis var. israelensis (B.t.i.) and temephos in
      controlling the pest blackfly Simulium chutteri Lewis along the middle Orange
      River between 1990 and 1995, was assessed. Larvicides were applied by helicopter
      to rapids and riffles between Hopetown and Onseepkans, a river distance of 807
      km. Larvicidal efficacy was based on the change in larval abundance at selected
      sites before and after each treatment. The success of the control programme was
      assessed independently by local farmers, who ranked adult blackfly annoyance on a
      4-point scale. Before treatment, blackfly annoyance showed consistent peaks in
      spring, and sometimes in autumn, and levels were unacceptably high for between 17
      and 36 weeks of the year. After treatment started, blackfly annoyance levels were
      reduced significantly. The number of annual treatments necessary to reduce
      blackfly annoyance to acceptable levels was highly variable (3-13), and depended
      on river conditions, as well as the efficacy and timing of each treatment. During
      low-flow conditions (< 50 m3/s), applications became increasingly difficult in
      braided sections of the river, and dosage calculations were inaccurate because of
      local abstraction and return flows. Both larvicides worked well in winter (water
      temperature 11-13 degrees C). Control of the spring outbreak can be planned well
      in advance, with the first treatment starting in mid July. A flexible protocol is
      required to control outbreaks at other times of the year. We recommended the use
      of B.t.i. for most applications, with increased dosages during algal blooms (>
      1500 cells/ml). The use of temphos in the Orange River should be considered only
      during algal blooms or when flows exceed 300 m3/s. We conclude that helicopter
      application of larvicides is an effective method or controlling blackflies, along
      the middle Orange River.

PMID- 9173361
TI  - Spatial and temporal variations in the commencement of seasonal activity in the
      Karoo paralysis tick, Ixodes rubicundis.
AB  - Successful prophylaxis of paralysis, induced in small stock by feeding female
      Ixodes rubicundus, is dependent on the accurate determination of the commencement
      of seasonal activity by the tick. The commencement of this activity was recorded
      for 11 consecutive years on a farm in the south-western Free State, South Africa,
      and for shorter periods on other farms, some of these in regions with markedly
      colder climates. The colder the mean minimum atmospheric temperatures during the
      2 months preceding the start to tick activity, the earlier it commenced. This
      could differ by 4 weeks from year to year on the same farm. In a region with a
      low effective temperature activity commenced between 3-8 weeks earlier than in a
      region with a higher effective temperature.

PMID- 9173362
TI  - Immunophenotypic classification of canine malignant lymphoma on formalin-mixed
      paraffin wax-embedded tissue by means of CD3 and CD79a cell markers.
AB  - Canine malignant lymphoma (CML) is a common lymphoid tumour. Identification of
      the immunophenotype is of prognostic importance: T-cell lymphomas have a worse
      prognosis than B-cell lymphomas. Until recently, identification of T- or B-cell
      lymphomas was undertaken by means of flow cytometry or fluorescent
      immunocytochemistry on frozen sections. Whilst valid in the research field, these
      methods are impractical for routine diagnostic histopathology in CML.
      Commercially available CD3 antibody has been successfully employed in T-cell
      identification in dogs in formalin-fixed paraffin wax-embedded tissue sections,
      but the lack of a B-cell marker has been a hindrance until the recent
      introduction of a commercially available pan-B cell marker, CD79a (DAKO M7051),
      suitable for diagnostic application upon formalin-fixed paraffin wax-embedded
      material. Antibody markers to CD3 and CD79a show cross-reactivity across species
      lines for B cells and T cells respectively. In this group of five selected canine
      cases, two were identified as B-cell and the other three as T-cell lymphoma, by
      means of CD3 and CD79a. To the best of our knowledge application of CD79a in
      cases of CML has not been reported.

PMID- 9173363
TI  - Culicoides (Diptera:Ceratopogonidae) associated with livestock in the
      Onderstepoort area, Gauteng, South Africa as determined by light-trap
      collections.
AB  - In 54 light-trap collections made at 28 sites in the Onderstepoort area a total
      of 178,941 Culicoides midges of 35 species was collected in March 1988; the
      survey was repeated at 26 sites in September and yielded 19,518 Culicoides of 24
      species. The number of Culicoides species collected totalled 38. C,imicola was
      the most abundant species at 27 of the 28 sites sampled, and accounted for 88%
      and 67% of all midges collected in the two months respectively. This study not
      only confirms that C. imicola is widespread and abundant in the greater
      Onderstepoort area, but also that its numbers correlate positively with the
      historical prevalence of African horse sickness (AHS) and bluetongue (BT)
      locally. The high numbers of C. imicola make Onderstepoort the ideal site for the
      study of its laboratory vector capacity. The relatively low numbers of Culicoides
      spp. other than C. imicola in the Onderstepoort area, will severely limit studies
      on their roles in the transmission of arboviruses. The origin of the blood-meals
      of 1338 engorged Culicoides belonging to 13 species was determined by means of
      cross-over electrophoresis precipitin test; C. imicola fed on cattle, horses,
      sheep of pigs, Four other Culicoides species showed a similarly wide host range.

PMID- 9173364
TI  - Photosensitivity in South Africa. IX. Structure elucidation of a beta-glucosidase
      treated saponin from Tribulus terrestris, and the identification of saponin
      chemotypes of South African T. terrestris.
AB  - Saponin C, a beta-glucosidase-treated saponin isolated from ethanol-water
      extracts of a South African collection of Tribulus terrestris, was shown by one-
      and two-dimensional NMR spectroscopy to be ruscogenin 1-O-alpha-L-rhamnopyranosyl
      (1-->2)-beta-D-6)-acetylglucopyranoside++ +. GC-MS analysis of the hydrolysed
      ethanol-water (4:1) extracts of T.terrestris specimens from two of four sites,
      revealed high levels of ruscogenin and potentially lithogenic diosgenin saponins.
      Specimens from two other sites contained non-lithogenic saponins derived
      predominantly from tigogenin, neotigogenin, gitogenin and neo-gitogenin.

PMID- 9173365
TI  - The intestine and endocrine pancreas of the African elephant: a histological
      immunocytochemical and immunofluorescence study.
AB  - Histological, immunocytochemical and immunofluorescence methods were employed to
      study the intestine and endocrine pancreas of the elephant. The histological
      findings were in line with those in monogastric mammals. In the mucosa of
      intestine, endocrine cells were immunoreactive to somatostatin, gastrin, CCK,
      GIP, secretin, motilin, glucagon and NPY. Nerve cells immunoreactive to
      somatostatin, substance P, VIP, PHI, NPY, bombesin and CGRP were detected. No
      immunoreactivity to neurotensin was observed, islets of the pancreas had insulin
      cells in their cores and glucagon and somatostatin cells in their mantles. The
      antisera employed failed to demonstrate PP cells in the pancreas, but NPY
      immunoreactive cells were present.

PMID- 9173366
TI  - Distribution of viral antigen in tissues of new-born lambs infected with Rift
      Valley fever virus.
AB  - The distribution of Rift Valley fever (RVF) viral antigen was studied by
      immunohistochemistry in the liver, spleen, prescapular lymph node, lungs and
      kidneys ot eight experimentally infected new-born lambs and in four new-born
      lambs that died of RVF during the 1974-75 RVF epidemic. The eight experimentally
      infected lambs were euthanazed at 6, 12, 18, 24, 30, 33, 48 and 51 h post
      infection (p.i.), respectively. Immunohistochemical staining utilized polyclonal
      hyperimmune mouse ascites fluid to RVF virus and peroxidase-diaminobenzidine was
      substrate. Virus antigen was most prominent in the liver and was detected as
      early as 18 h p.i. in the cytoplasm of hepatocytes that were sparsely scattered
      throughout the lobules. At 24-33 h p.i. antigen was also present in or adjacent
      to small foci of hepatocellular necrosis. At 48-51 h p.i. and in one of the field
      cases, positive staining was widespread and most consistently present in the
      cytoplasm of large numbers of degenerated or necrotic hepatocytes and in a new
      acidophilic bodies. Immunohistochemical staining was rarely observed in
      hepatocyte nuclei. Almost diffuse histochemical staining was observed in
      disintegrated cells and in the cytoplasm of necrotic hepatocytes throughout the
      liver in the other three field cases with pannecrosis; only the primary foci
      necrosis and a narrow periportal rim of intact hepatocytes did not stain. No
      staining was observed in bile duct epithelium, endothelial and Kupffer cells in
      the initial stages of Infection, supporting the contention that hepatocytes
      constitute the primary site of RVF virus replication in new-born lambs. Few cells
      stained positively in the spleen, prescapular lymph node, lungs and kidneys.

PMID- 9173367
TI  - [Helicobacter pylori and ulcer disease].
AB  - Helicobacter pylori (H. pylori) is the most common human gastrointestinal
      pathogen, infecting almost 50% of human population. By our present knowledge H.
      pylori is the cause of chronic active B type gastritis and the bacterium is
      accepted as a major pathogenetic factor of peptic ulcer disease. The prevalence
      of H. pylori positivity is about 95% in duodenal ulcer patients, in gastric ulcer
      patients 70-90% H. pylori positivity can be detected. The gastric mucosal barrier
      is weakened by the bacterial urease enzyme and vacoulating cytotoxin production.
      Special inflammatory and immunological processes as well H. pylori induced acid
      production increasing effects are also contributing to the pathogenesis of peptic
      ulcer disease. In the diagnosis of H. pylori the biopsy based invasive methods
      like histology and rapid urease test are offering the highest sensitivity and
      specificity. For controlling the eradication effect the most appropriate method
      is the isotope labelled urea breath test. In the lack of optimal H. pylori
      eradicating drug several combined therapeutical methods are available at present.
      Among the wide range of H. pylori eradicating regimens the macrolide or beta
      lactam antibiotics with nitromidazole and effective antisecretory drugs offer the
      highest eradication effect. In practice the low dose, short term administration
      of those compounds are most widely used presently.

PMID- 9173368
TI  - [The effect of calcitriol on renal anemia in patients under chronic
      hemodialysis].
AB  - The authors reached the suppression of serum intact parathormone (iPTH) by
      calcitriol therapy in chronic hemodialyzed patients with secondary
      hyperparathyroidism. Parallel with the depression of iPTH levels it was enough a
      lower doses of recombinant human erythropoietin (Rh-EPO) to maintain the target
      hematocrit, while on two patients non-treated with Rh-EPO they founded an
      improvement in moderate anemia. Their data confirm that the calcitriol is an
      effective drug in the treatment of secondary hyperparathyroidism. The results
      speak in favour that in the improvement of renal anemia on regular hemodialysis
      patients play an important role the suppression of serum iPTH levels too.

PMID- 9173369
TI  - [Analysis of antibiotic use based on case histories].
AB  - Type and dose of antibiotics, length and purpose of therapy was retrospectively
      collected from case histories of the 2230 patients who were discharged from a
      district general hospital between January 1 and 31, 1995. The suitability of each
      antibiotic for its stated purpose was compared with the current therapeutic
      recommendations, guidelines and literature. 24.6% of patients received
      antibiotics. 83.9% of the 728 courses was monotherapy, 16.1% was combined
      therapy. 82.7% of the 852 prescriptions was empiric, 7.5% directed against an
      identified microorganism and 9.8% was prophylactic. 596 microbiological samples
      of 272 (49.5%) patients were sent to the laboratory. Infections of lower and
      upper airways, urinary tracts, wounds and abdominal organs were most frequently
      diagnosed. Majority of utilized antibiotics were broad spectrum beta lactams.
      5.3% of patients suffered from hospital acquired infections. 23.8% of
      prescriptions were determined as unnecessary. Problems of inappropriate
      antibacterial spectrum (11.0% of prescriptions), negligence of pharmacokinetics
      (6.1%), long duration of therapy (7.2%) and underdosing (6.1%) were also
      frequent. Authors emphasize the importance of the monitoring drug utilisation,
      the introduction of hospital diagnostic and therapeutic protocols in order to
      improve the antibiotic usage.

PMID- 9173370
TI  - [Experiences with a new vacuum-accelerated microwave histoprocessor].
AB  - Methods of microwave and vacuum accelerated fixation, dehydration and paraffin
      embedding are described. They can be carried out in a new type of vacuum and
      temperature stabilizable microwave histoprocessor: MFX-800. The whole
      histoprocessing lasts 3.5-5.5 hours depending on the thickness of the tissue
      blocks. Preserved structural detail, intensive staining and good antigen
      preservation were achieved with various tissues. This new histoprocessing
      facility can be highly recommended for pathology laboratories interested in
      speeding up the processing procedure, as well as in immunohistochemistry.

PMID- 9173371
TI  - [Emergency coronary revascularization using various arteries].
AB  - Authors present the case report of a young man with advanced coronary artery
      disease of the left main trunk and the big branches of the left coronary system
      leading to sudden onset of many ventricular fibrillations associated with
      unconsciousness requiring several reanimations. The condition was treated with
      coronary artery surgery with the usage of three different arterial conduits
      (right radial artery, right gastroepiploic artery as free grafts and the left
      internal mammary artery in situ) with an additional saphenous vein bypass graft.
      Details of surgical procedures as well as the documents of the early
      postoperative course and of the 1 month follow up are given.

PMID- 9173372
TI  - [Basic training st the Gyor-Mosom-Sopron County Free University-- a national
      model for the training and advanced education of family physicians].

PMID- 9173373
TI  - [Anaplastic large cell lymphoma based on our clinicopathological cases].
AB  - CD30(Ki-1) positive anaplastic large cell lymphoma (ALCL) is a distinct entity,
      in which the monoclonal antibody-positivity against the CD30(Ki-1) antigen of
      tumour cells has a diagnostic value. The histological subtypes of ALCL show also
      certain clinical differences. Except for some pediatric cases and cutaneous forms
      clinical outcome is very unfavourable despite of the various treatment methods.
      In this prospective study (follow-up of 11-60, median 16 months)
      clinicopathological data and treatment results of fifteen adult patients with
      ALCL were analysed, Mean age was 46 (16-69) ys with a bimodal tendency and a
      distinct female: male ratio (3:2) was observed. Early clinical stages (I-II/A-B,
      eight patients) dominated, and two main groups could be distinguished
      histologically (Hodgkin-related, ALCL-HR and common type, -CT in eight and seven
      patients), respectively. In all histological specimens CD30 antigen expression
      was detected. Additional immunophenotyping was performed in five cases (two 0
      variant, two of B-cell and one of T-cell origin), respectively. A bulky disease,
      mainly in the mediastinum was observed in six cases, and a primary
      gastrointestinal localization in two other patients. In the treatment of these
      high grade malignant lymphomas a combination of cobalt irradiation and aggressive
      chemotherapy was applied (in elder the CHOP-regimen, in younger patients mainly
      the Pro-MACE-Cyta-BOM-protocol). In one relapsed younger patient autologous bone
      marrow transplantation was also performed. A complete or partial remission was
      achieved in thirteen patients (86.6%) but six patients expired after only a short
      response period to therapy. Overall survival was 19, whilst disease-free survival
      revealed to be 15 months. Eight of their living nine patients have a durable
      complete remission. Due to residual mediastinal mass after radiotherapy in three
      cases a permanent radiological follow-up is needed. Advanced age and clinical
      stages are considered to be unfavourable, whilst histological subtypes were
      indifferent prognostic factors, as well. Favourable results in therapy and
      durable complete remission in younger patients are probably caused by the their
      better tolerance of third-line aggressive chemotherapy.

PMID- 9173374
TI  - [Significance of early echocardiography in acute myocardial infarct].
AB  - The authors examined the role of echocardiography performed in the acute phase of
      the myocardial infarction, within 72 hours after hospitalization in order to
      reveal the diagnosis, to detect of the complications and mortality in hospital.
      512 consecutive patients were examined by echocardiography. All of them were
      younger than 70, and they were treated at our department between 1st January,
      1991 and 31st December, 1994 with acute myocardial infarction. In 34 cases the
      infarction was without Q wave. The most severe left ventricular wall motion
      abnormality was dyskinesis in 53, akinesis in 390, hypokinesis in 49 cases,
      normokinesis was detected in 20 patients. The detection of the wall motion
      abnormality helped to diagnose 27 right ventricular infarctions, 58 reinfarctions
      and 21 acute myocardial infarction with left bundle branch block. 43 patients
      (8.4%) died during the treatment. In all cases the pathological examination
      verified the diagnosis of the acute myocardial infarction, and at 4 patients free
      wall rupture had been revealed. Among the deceased left ventricular dilatation
      (16/43 versus 75/469, p < 0.001), ejection fraction lower than 40% (14/43 versus
      52/469, p < 0.001), left ventricular wall motion abnormality index (16 segments;
      1 = normokinesis, 2 = hypokinesis, 3 = akinesis, 4 = dyskinesis, 5 = aneurysm)
      higher than 2.0 (27/43 versus 93/469, p < 0.001), dyskinesis (12/43 versus
      41/469, p < 0.001), pericardial effusion thicker than 5 mm (7/43 versus 31/469, p
      < 0.05), and right ventricular infarction (6/43 versus 21/469, p < 0.05) occurred
      significantly more often. Dyskinesis is a bad prognostic factor even in the case
      of good left ventricular function. According to the opinion of the authors,
      echocardiography performed at the early stage of acute myocardial infarction,
      increases the safety of the diagnosis and calls the attention to the patients
      with high risk.

PMID- 9173375
TI  - [Hypertension in the newborn].
AB  - Hypertension in the neonatal period and early infancy in underdiagnosed due to
      the absence of the attention and the difficulties of diagnostic procedures.
      Although the neonatal systemic hypertension is rare, but it can, cause serious
      medical problem with an increased risk of cardiorespiratory failure, cerebral
      distress and growth failure. Arising questions in their daily work got the
      authors to review the literature. They analyse procedures and criteria of
      measuring of neonatal blood pressure and values of neonatal hypertension. In
      addition to a list of the origin of hypertension they discuss the most frequent
      causes. The symptoms of the neonatal hypertension and the examinations were drawn
      up a chart. By choosing of the therapy is accented the important of knowing
      pathomechanism, recommended drugs, their doses and limits due to the side
      effects. Time of the diagnosis of hypertension and adequate treatment influence
      the prognosis fundamentally. The authors call the doctors attention to the early
      measure of blood pressure, clear the etiology and the permanent control of
      touched organs.

PMID- 9173376
TI  - [Screening of sexually transmitted diseases (Mycoplasma hominis, Ureaplasma
      urealyticum and Chlamydia trachomatis) in young women].
AB  - The author searched for sexually transmitted Ureaplasma urealyticum, Mycoplasma
      hominis and Chlamydia trachomatis infection among young females under 30. Out of
      the 400 women examined (including 86 primigravidas) 46 percent, and out of the
      pregnant women 52.3 percent proved to be colonized by one of the above pathogens.
      11 percent carried Mycoplasma hominis, 44.75 percent Ureaplasma urealyticum and
      7.75 percent Chlamydia trachomatis. Positivity was more frequent among those
      having several partners and those not using condoms regularly. The author thinks
      the pathogen infection rate found can be one of the main causes of urogenital
      inflammations, fertility problems and premature deliveries. Due to the earlier
      and earlier start of sexual lives, more effective sanitary/sexual education will
      be needed.

PMID- 9173377
TI  - [Simultaneous occurrence of small intestine mesenchymoma and rectal carcinoma].
AB  - The authors report the presentation of a rare small bowel mesenchymoma at the
      jejuno-ileal transition found during the operation of an adenocarcinoma of the
      recto-sigmoid junction. They discuss the pathology and clinic of the benign
      mesenchymal tumors of the small intestine.

PMID- 9173378
TI  - [The enzyme catalase and acute pancreatitis].

PMID- 9173379
TI  - [New possibilities in the management of pre-eclampsia: NO-donor compounds].

PMID- 9173380
TI  - [Anthracosis in members of the aristocracy and mummies in Hungary].

PMID- 9173381
TI  - [Interpretation of the teachings of Endre Hogyes in the light of today's health
      policy].
AB  - In the E. Hogyes memorial lecture the author has given a comparative analysis
      between the concepts of Hogyes at the end of the last century concerning gradual
      and postgradual medical education, public life, and health policy and the actual
      problems in Hungary. It has been mentioned also some report of leading foreign
      experts in topics mentioned above.

PMID- 9173382
TI  - [Coumarin combined with low-dose acetylsalicylic acid in the prevention of
      thromboembolic complications in patients with mitral and aortic valve
      prostheses].
AB  - Authors studied the effect of coumarin, and its combination with low-dose (125
      mg/day) acetylsalicylic acid in the prevention of thromboembolic complication
      during a 10-year period (average 4.7 years) in a randomized trial of 296 patients
      aged 18-60 year with tilting disc type prosthetic heart valve (159 mitral and 137
      aortic) in sinus rhythm. In the group treated with coumarin (152 patients, 743.4
      patient-years) 4 cases (2 of them fatal) of valve thrombosis, 12 cases of
      peripheral embolism and 9 cases (3 intracranial, 3 among them fatal) of major
      bleeding were observed; in the group treated with coumarin plus acetylsalicylic
      acid (144 patients, 638.7 patient-years) 2 cases (1 of them fatal) of valve
      thrombosis, 4 cases of peripheral embolism and 14 cases (3 of them fatal) of
      major bleeding were observed. In the case of valve thromboses the difference
      between the two groups was non-significant but still clinically remarkable;
      peripheral embolism occurred in significantly higher number (p < 0.05). There was
      no statistically significant difference of bleeding complications between the two
      groups. The results suggest that the combination of coumarin plus low-dose
      acetylsalicylic acid is more effective in the prevention of thromboembolic
      complications in patients with mitral and aortic prosthetic heart valve than
      coumarin alone; the danger of bleeding complications seems to be acceptable with
      adequate control.

PMID- 9173383
TI  - [Limb-body wall malformation complex: an unusual developmental abnormality of the
      abdominal wall. Case report, clinicopathological and etiological implications].
AB  - Anterior abdominal wall defects are not too rare between developmental
      abnormalities. A case of abdominal wall defect associated with complex
      malformations diagnosed prenatally is reported in the paper. In the present case
      of limb-body wall complex a right sided abdominoschisis was associated with
      rotational abnormality of the lower limbs, clubfoot, scoliosis, meningomyelocele,
      lack of developed pelvic organs, consecutive dilatation of the upper urinary
      tract, anal atresia, lack of external genitalia, lack of diaphragm and
      hypoplastic lungs. Review of the pertinent literature has revealed over 100 cases
      that clearly indicate the possible phenotypic variation of the limb-body wall
      complex. These data add further evidence to support the existence of two
      different phenotypes and possibly pathogenesis under the heading of limb-body
      wall complex. The three principal theories on the possible aetiology of the
      complex are also discussed. Because the limb-body wall complex is incompatible
      with life, it is important to diagnose the lesions prenatally, and to
      differentiate them from other anterior abdominal wall defects. Serum alpha
      fetoprotein measurement, and ultrasonographic examination are the key to prenatal
      diagnosis.

PMID- 9173384
TI  - [PATHYPRE: Pascal program for the estimation of the individual course of patients
      with papillary thyroid cancer].
AB  - Individual survival probability estimation provided by mathematical models based
      on cases with a known clinical course is of great help as concerns the treatment
      strategy decision relating to malignant tumours. Data on four hundred Hungarian
      papillary thyroid cancer patients were used together with the Markov method to
      construct a survival model (Orv. Hetil. 1996 137: 1067-1078,) for prediction of
      the individual clinical course of newly diagnosed cases for 30 years following
      surgical intervention. Input data included the age, the primary tumour size and
      extent (pT), distant metastasis at presentation, the extent of the surgical
      intervention, the external irradiation dosage and the degree of TSH suppression.
      From the input data, the PATHYPRE program can estimate the individual
      local/regional/distant relapse-free survival probabilities and overall cause
      specific survival probability. The survival probabilities may be predicted for
      variations in the treatment parameters, and thus the model helps in the selection
      of the most appropriate therapy for the patient. The PATHYPRE software is
      available through the Internet connections on the home page of the National
      Institute of Oncology, Budapest (www.oncol.hu).

PMID- 9173385
TI  - [Relapsing polychondritis associated with myelodysplasia and acute eosinophilic
      leukemia].
AB  - Authors report a case in which relapsing polychondritis had been diagnosed two
      years before myelodysplastic syndrome developed and terminated in eosinophilic
      leukemia. The observation that relapsing polychondritis may precede
      myelodysplasia is not in concordance with some of the previous reports regarding
      relapsing polychondritis as a paraneoplastic phenomenon of myelodysplastic
      syndrome. The terminally developed eosinophilic leukemia is not supposed to be a
      blastic phase of the underlying myelodysplasia, much rather a second malignant
      process. This opinion may be confirmed by the early presence of blast cells in
      the myelodysplastic process without eosinophilia. It seems interesting to note
      that both our patient and his daughter suffered from diseases of autoimmune
      origin: acquired vitiligo and subacute cutan lupus erythematodes, respectively.

PMID- 9173386
TI  - [Antithrombotic therapy of arterial diseases].

PMID- 9173387
TI  - [Prognostic factors in radiotherapy of supraglottic cancer].
AB  - In 971 patients with squamous cell carcinoma of supraglottic larynx several
      clinical and physical prognostic factors were evaluated. There were 55% of
      patients with advanced primary tumours and 71% of patients with no regional neck
      metastases. All patients were irradiated radically using external megavoltage
      beam. The total dose was in range 60-70 Gy for 95% of patients. The 3-year local
      control rate and 3-year overall in whole group were 41% and 50% respectively.
      Clinical stage, haemoglobin level at the end of treatment, overall treatment
      time, sex and total dose were estimated as an independent and important
      prognostic factors for the outcome in radiotherapy of supraglottic larynx cancer.

PMID- 9173388
TI  - [Multiple primaries in head and neck malignant neoplasms].
AB  - Multiple primary neoplasm has developed in 70 patients with head and neck cancer
      who were treated in Otorhinolaryngology Department Medical Academy in Warsaw. Two
      primary neoplasm has been recognised in 63 patients, three independent tumors in
      7 patients. The most common site for a first tumor was laryngeal carcinoma, for a
      second - lung, skin and tongue. The squamous cell carcinoma was the most common
      in the first as well as in the second malignancies.

PMID- 9173389
TI  - [Endoscopic ultrasound probe applications for diagnosis of the oral cavity and
      throat tumors].
AB  - Assessment of neoplastic lesions situated inside palatinal tonsils and tongue may
      cause a lot of difficulties. Bringing into practice diagnostic tools such as:
      transcutaneous ultrasound, CT, MRI have met numerous limitations and obstacles.
      Apart from restrictions set by anatomical borders, other drawbacks of methods
      mentioned above are: high cost of single examination, expensive equipment and
      difficulties of access. In this paper the results of examination of 20 tongue
      tumors and 23 tonsil tumors carried out by means of endoral ultrasound are
      presented. Endoral ultrasound provided evaluation of size, localisation,
      extension and delimitation of and detect small nodules satellite to the
      predominant tumor mass. Evaluation of lesion echostructure enables to
      differentiate the tumor nature and advises to plan other diagnostic procedures.

PMID- 9173390
TI  - [The use of mucolytic preparations (Mucosolvan) in nasal and paranasal sinuses in
      children].
AB  - In recent years there has been observed an increase in the infections of nose
      cavity and paranasal sinuses. This phenomenon is connected with a
      multidirectional alergization of the environment also with the insufficiency of
      conservative and surgical treatment. Messerklinger's research concerning cilial
      movements of mucosa in nasal and paranasal sinuses together with his endoscopic
      experiments are the basic for modern therapy of nasal and paranasal sinuses. In
      this paper 40 cases of acute and chronic inflammation of paranasal sinuses in
      children between 3 and 16 years of age were presented. In all cases regardless of
      the used method of conservative or surgical treatment children were given
      mucolytic preparations in the form of Mucosolvan by Boehringer Ingelheim. In all
      observed cases we noticed the shortening of the normal period of the
      antiinflammatory antibiotic treatment. A part from that, mucolitic preparations
      due to the decrease of mucous adhesiveness to the walls of paranasal sinuses
      allow for its evacuation largely decreasing the pain. After FESS treatment, the
      administration mucolytic preparations causes a factor regeneration of cilial
      epithelium, proper functioning of cilia and the speeding of mucocilial trnasport,
      which makes the recovery of an ill child much quicker.

PMID- 9173391
TI  - [Diagnostic and prognostic value of p53 oncogene and the selected neoplastic
      markers (Ki67, PCNA, DNA ploidy) of the ultrastructure in patients with laryngeal
      cancer].
AB  - A comparison was performed of staining intensity of immunohistochemical
      proliferating antigens (p53, PCNA, Ki67), DNA flow cytometry and ultrastructure
      of the carcinoma cells in 120 cases of laryngeal cancer. Clinically very advanced
      tumors were in majority (T3 - 43%, T4 - 18%). A 5 graded scale was adapted to
      evaluate the level of immunohistochemical staining of the carcinoma cell nuclei.
      A positive staining was obtained in 70% for p53, 57% for Ki67 and in 80(2/3) for
      PCNA. 62% of the cases were DNA diploid and 38% DNA aneuploid. The DNA diploid
      carcinomas were accompanied by the enlargement of the cell nuclei, preserving of
      the nuclei's wide margins of heterochromatine, enlargement of the nuclear area
      and increase of the number of nuclei. In the aneuploid-polyploid cancer the
      nuclei had a substantial polymorphism with large cleaved nuclei and with
      significant variation in size, and with nuclear envelope. A frequent finding was
      euchromatization of chromatine. Dense chromatine appeared in the form of small
      clumps spread over the whole area of these irregular nuclei. Enlargement and
      activation of nucleoli occurred. There was a positive correlation (Chi-square)
      between T- and N-stage and immunohistochemical staining. There was also a
      positive correlation in staining intensity between p53, Ki67 and PCNA. There is
      also strong correlation between these markers of proliferative activity and the
      degree of aggressiveness of the tumour.

PMID- 9173392
TI  - [Impedance measurements of the middle ear volume with tympanic membrane
      perforation].
AB  - The measurement principles of pneumatic spaces of the middle ear were presented
      in this paper. According to the literature the controversial opinions of other
      authors were analysed. On the base of two cases changes of the middle ear volume
      in pathological states were presented. The value of middle ear volume estimation
      preoperatively was emphasized.

PMID- 9173393
TI  - [Congenital auricular fistula imitating otogenic complication].
AB  - A 25-year-old man was brought in after a preliminary diagnosis of chronic,
      exacerbated right otitis media. Following our physical examination a granulated,
      purulen ear pit was found out behind the right auricle. At the base of the helix
      a non-purulent external opening of the ear pit was found out. The operation
      showed that we had to do with preauricular fistula embracing the auricle from
      above and ending with a purulent cyst above the upper back wall of the external
      auditory meatus. The ear pit and cyst were extirpated as a whole. A 1,5-year
      observation period has not shown any recurrence of the disease.

PMID- 9173394
TI  - [Tests of auditory perception of speech (TAPS) for children with cochlear
      implants].

PMID- 9173395
TI  - [Device for controlling hemorrhage in the nasal cavity].
AB  - Authors describe a controlling device in a nasal haemorrhage which has been
      accepted as the registered model No: PL 52469-Y1. The presented device has been
      applied in many cases of nasal haemorrhage in patients in First Department of
      Laryngology of the Silesian University School of Medicine in Katowice.

PMID- 9173396
TI  - [Report from the second international symposium on the topic "Reconstruction of
      larynx and trachea", Monte Carlo, Monaco, May 22-26, 1996].

PMID- 9173398
TI  - Neurocardiogenic Syncope. Proceedings of an international symposium. Lansdowne,
      Virginia, September 27-29, 1996.

PMID- 9173397
TI  - Cardiac Electrophysiology: The Duke Perspective. Proceedings of a symposium.
      Durham, North Carolina, April 26-28, 1996.

PMID- 9173399
TI  - [Diathesis and predisposition. A molecular reappraisal of the mode of reacting].
AB  - The identification of the causes of important infectious and hereditary diseases
      became scientifically clear in the last years of the nineteenth century and in
      the first years of the twentieth. Through many centuries, the lack of etiologic
      knowledge regarding diseases has extraordinarily enhanced the value of the
      concept of predisposition so that "diathesis" helped to "explain" many forms of
      morbidity. Several discoveries as to the real "causes" of diseases, however, led
      to a critical downgrading of its value. But in-depth knowledge regarding the
      proteins controlled by genes of the "major histocompatibility complex" (MHC, HLA)
      in man was followed, a few years later, by the demonstration of the fact that
      carriers of particular alleles are exposed to higher risks of contracting certain
      diseases than non-carriers of these molecules. A new key for interpretation-this
      time, a genetic and molecular one-was thus offered for the concept of
      "predisposition". Actually, man's HLA-associated molecular individuality induces
      and causes an extraordinarily personal way of reacting to various stimuli. An
      obvious consequence of this is not only that man, having become aware of his
      "molecular uniqueness" (which is significantly HLA-related), can view himself as
      a "biological Ego" but, most of all, that some of his predispositions towards
      becoming ill may be ascribed to some of his individual molecular
      characterizations. Thus, the onset and the course of many diseases would be
      viewed as the effect of a given "way of reacting". This could be recognized as
      the true essence of diathesis, 18 centuries after Galen.

PMID- 9173400
TI  - [Latex: an allergological emergency? An update and outlook].
AB  - Allergy to latex has become an increasing and clinically important problem during
      last years. Natural rubber latex (NRL) allergy has been acknowledged as a major
      occupation problem among health-care workers. More recently, NRL allergy also
      occurs in children with spina bifida and in atopic children. Even patients
      allergic to various fruits, such as banana and avocado may experience allergic
      reaction from NRL and vice versa. Different latex allergens have been
      characterized at the molecular level using varied techniques and heterogeneous
      latex materials. Little is known about prevalence and clinical relevance of latex
      sensitization and allergy in the general population although the incidence is
      increasing in children. The wide spectrum of symptoms of NRL allergy range from
      mild contact urticaria to asthma and anaphylactic reactions. History is an
      integral part to identify latex allergy. Different tests (skin prick tests, RAST,
      Pricking, Use test) have been used to objectively supplement the history. Latex
      allergy must be prevented by the standardization of medical gloves including the
      labeling of latex content and allergenicity; furthermore the industrial
      strategies may also develop new methods of less allergenic gloves and other NRL
      products.

PMID- 9173401
TI  - [Food allergy: recent findings].
AB  - Food allergy induces in infancy and childhood a large variety of symptoms which
      may be trivial in many children, chronic and severe in others and even fatal in
      rare cases. According to double-blind placebo controlled oral food challenges,
      cow's milk, egg, wheat and fish are the most common offending foods. Elimination
      of the offending food(s) is imperative for the management of children with food
      allergy. An appropriate formula without cow's milk proteins and allergenic
      epitopes should be given to infants with cow's milk allergy. Breast feeding and
      selected weaning after the sixth month of life are recommended for the prevention
      of food allergy in atopic prone babies.

PMID- 9173402
TI  - [Allergy and infections: a rediscovery for pathogenesis and therapy].
AB  - The relationship between allergy and infection is well known. However only the
      recent discover of the mechanisms underlie to allergic inflammation gave us the
      interpretative key to understand the reciprocal influence. In the onset of
      allergic diseases infections may play whether a predisposing or protective role,
      while in the induction of relapses, infections play the major role, priming the
      inflammation, which among allergic children immediately, switches in allergic
      inflammation.

PMID- 9173403
TI  - [A correlation between food allergy, the autonomic nervous system and the central
      nervous system: a study of 8 patients in childhood].
AB  - The aim of our study was demonstrate the correlation between immunoallergic
      system, autonomous nervous system (SNA) and central nervous system (SNC). Eight
      children allergic to food and with asthma, damage of handwriting, deambulation
      and behaviour were deprived of food allergens. The RAW (indicator of SNA
      activation) diminished and the respiratory flow increased. The neurologic
      symptomatology improved. The reintroduction of food allergens induced
      reappearance of asthmatic and neurologic symptomatology.

PMID- 9173404
TI  - [A proposal for establishing a maternal-pediatric department in a general
      hospital].

PMID- 9173405
TI  - [Thrombocytopenia, arthritis and enteropathy: a casual association or the
      expression of a unique entity?].
AB  - The arthropathy of inflammatory bowel disease (IBD) is a noninfectious arthritis
      occurring before or during the course of either regional enteritis or ulcerative
      colitis. Two patterns of joint disease are described: a chronic asymmetric
      oligoarthritis affecting peripheral joints, and a spondylo-sacroiliitis similar
      to the idiopathic type. Different criteria for diagnosis and classification (ACR
      and EULAR) of arthropathies associated with IBD are used and this is not helpful
      in order to a correct nosography. An unusual case of ulcerative colitis with
      thrombocytopenia and oligoarticular arthritis at onset, 4 and 2 years before the
      assessment of IBD, is reported. Moreover the arthritis had characteristics much
      more similar to a juvenile chronic arthritis (JCA) with pauciarticular onset of
      type I (FR-; ANA+) than to an enteropathic arthropathy.

PMID- 9173406
TI  - [The prenatal diagnosis and early endoscopic section of ureterocele].
AB  - The endoscopic incision of ureterocele in children is still a controversial
      procedure. In two Departments of Pediatric Surgery, between January 1990 and
      December 1994, 47 patients (34 females, 13 males), for a total of 53
      ureteroceles, underwent endoscopic incision of the ureterocele as the primary
      form of treatment; 41 ureteroceles were in duplex kidney. In 33 cases (70%) the
      prenatal ultrasound had observed hydronephrosis or duplex kidney or the presence
      of the ureterocele; these babies were free of urinary infection before treatment.
      45 of the 47 babies were less than 6 months old at the time of the endoscopic
      incision. Vesico-ureteral reflux developed in none of the single systems, and in
      32% of the duplex systems; however a preexisting reflux spontaneously disappeared
      in 41%. At 1 year follow-up the mean increase in renal parenchyma as evaluated at
      ultrasound was from 6.4 to 11.1 mm in single systems, and from 3.4 to 6.3 mm in
      duplex kidneys. Scintigraphy or urography showed a stable or improved renal
      function in all previously functioning units; 40% of the non-functioning units
      before section showed signs of function at 1 year follow-up. One to 3 years after
      section, 14 children underwent open surgery for persisting vesico-ureteral
      reflux, urinary infections or non-functioning unit: 9 ureteroneocystostomies and
      5 heminephrectomies were performed. The endoscopic incision is proposed as the
      early first treatment of ureteroceles, mainly in cases of prenatal diagnosis,
      possibly performed in the neonatal age. In the Authors' experience it has been
      effective in preventing sepsis in all patients and in preserving the renal
      function of the involved unit; surgery has been avoided in over 60% of cases and
      when necessary it has been safely postponed after more than 1 year of age.

PMID- 9173407
TI  - [Criteria for the evaluation of neonatal pain].
AB  - The common opinion about the painful sensation in newborn and in premature baby,
      is that the experience of pain begins since birth. One of the difficulties in
      taking care of pain in neonatology is the valuation of the symptom: actually
      there aren't enough sensitive and standard methods to define and quantify the
      pain of newborns and prematures babies. The authors illustrate two scales of pain
      valuation, that have been tested and then adopted by different french groups.
      These scales allow to examine respectively, the healthy newborn and the newborn
      after surgical care and permit also an objective measure of newborn malaise
      sensation. These scores need the valuation of clinical signs and physiological
      parameters that are sometimes neglected during the execution of invasive
      techniques; therefore these tables would awaken the sanitary staff to newborn
      expressions of pain or discomfort, allowing a best comprehension of baby's
      feelings and facilitating in this nursing and pharmacological interventions to
      relieve pain.

PMID- 9173408
TI  - [Neuropsychic development in children born with spina bifida].
AB  - The authors present the outcome of 42 patients operated at birth for closure of
      the spinal malformation. The age of patients at first observation ranged from 3
      months to 21 years (mean 8.3 years); 7 patients (16.7%) had a close spina bifida,
      35 (83.3%) had an open spina bifida and 30 (85.7%) of them developed
      hydrocephalus. The protocol included neurological evaluation, determination of
      development quotient using the Griffith's scale and intelligence quotient using
      the Wise-R scale. Adolescents underwent also the Blacky pictures test and Offer's
      interview. Verticalization and tutorial deambulation were achieved in 95.2% of
      patients; 76% of patients had a I.Q. > 90. The emotional situation was
      unsatisfactory in the majority of patients due to reduced autonomy and limited
      self-consideration.

PMID- 9173409
TI  - [Acute-phase proteins in appendicitis in childhood: new findings].
AB  - The diagnosis of acute appendicitis in children can be sometimes difficult. The
      monitoring of acute phase protein response has been suggested as an accurate
      diagnostic procedure in these patients. This response is an aspecific event
      caused by phlogosis, infections and traumatisms; it is accomplished by the
      hepatic release of "endogenous leukocytic mediators" (L.E.M.) among which can be
      remembered IL-6 and IL-7. The acute phase proteins can be distinguished into
      positive and negative factors. Many authors used the acute phase protein response
      in order to stratify the severity of disease, to evaluate the efficacy of therapy
      and to find out any complication. They actually think that this response is
      useful to draw up a prognostic index in each patient. This second part of a study
      started in 1994 is based on the evaluation of the preoperative acute phase
      proteins values in pediatric patients affected by acute appendicitis underwent to
      surgery. The results of the statistic analysis show the utility of the evaluation
      of these parameters in the preoperative period; in particular G.B. count and
      P.C.R. rates very early with significant statistics, while the other values
      change later and are more difficult to interpret.

PMID- 9173410
TI  - [Cystic-papillary neoplasm of the pancreas: a case report in childhood].
AB  - A solid and cystic tumor of the pancreas in a 11-year-old girl is reported. The
      child presented with abdominal pain and vomiting. A voluminous tumor, arising
      from the pancreas tail, was removed with distal pancreatectomy. These neoplasma
      occur predominantly in girls and young women, the prognosis is usually good in
      spite of histologic finding of apparent malignancy. The histochemical,
      immunohistochemical and electron examinations of this tumor show polymorphic
      differentiation, which means that part of the all can differentiate into duct
      epithelium, acinar or endocrine line. So up to, recently this tumor has been
      misclassified within other pancreatic tumors, and frequently has been managed
      with aggressive surgery. But as the neoplasm usually behaves like a very low
      grade malignancy, its complete removal is the treatment of choice for the tumors
      arising anywhere in the pancreas. The authors emphasize the importance of
      accurate diagnosis and of extirpative surgery in children with pancreatic
      malignancy.

PMID- 9173411
TI  - [Early-onset hyperthyroidism with muscle involvement: a report on a patient].
AB  - A case of Graves' disease in a 2 years child old is reported. He presented
      tachycardia, loss of weight, anxiety and gait abnormality. The serum free T3 and
      T4 and thyrotropin receptor antibodies values were elevated, TSH was not
      measurable. The EMG was abnormal with short duration motor unit potentials.

PMID- 9173412
TI  - [A case of severe malnutrition due to Ascaris lumbricoides infestation in a boy].
AB  - The authors report a case of a child three years old, with severe malnutrition as
      complication of Ascaris lumbricoides infection. Intestinal nematodes infect many
      of the world's children and constitute a formidable public health problem. The
      infected children may suffer nutritional deficits, serious illness and
      occasionally death. Although infestation is uncommon in our country, it should be
      considered in children with low social life.

PMID- 9173413
TI  - [Flexible contra rigid bronchoscopy for implantation of tracheobronchial
      prostheses (stents). Pro rigid bronchoscopy].

PMID- 9173414
TI  - [Flexible contra rigid bronchoscopy for implantation of tracheobronchial
      prostheses (stents). Pro flexible bronchoscopy].

PMID- 9173415
TI  - [Proportional assisted ventilation--advantages and limits of a new ventilation
      concept].

PMID- 9173416
TI  - [Surfactant administration and laterally independent positive pressure
      ventilation in acute lung failure and atelectasis after septic abortion. Case
      report].
AB  - We report the case of a 35 years old female patient suffering from Staphylococcus
      aureus induced abortion in the 7th/8th week of gestation. Sepsis with acute
      respiratory failure (ARDS) developed, which could be treated successfully.
      Pneumonia, caused by Pseudomonas aeruginosa, induced a recurrence of ARDS,
      complicated by a persistent incomplete atelectasis of the left lung. Independent
      ventilation of both lungs with increased pressure on the left side combined with
      bronchoscopy guided instillation of 1 g of bovine surfactant (Alveofact), caused
      improvement of arterial oxygenation and radiological signs, signalling airation
      of collapsed lung areas.

PMID- 9173417
TI  - [Pulmonary vasculitis: systematic aspects, pathogenesis and therapy].

PMID- 9173418
TI  - [Coincidence of pulmonary cryptococcoma in an immunocompetent patients with a
      chondrohamartoma and chronic tuberculoma--differential diagnostic considerations
      concerining pulmonary coin lesions].
AB  - Of primary importance in the differential diagnosis of multiple circular foci in
      the lungs are the lung metastases. This study involves a patient with three
      circular foci, each of which could have been metastases. They proved, however, to
      be a rare coincidence of three benign lung affections, namely, an old
      tuberculoma, a chondrohamartoma, and a seldom encountered pulmonary
      cryptococcoma. Computerized tomography utilizing the spiral technique was
      valuable diagnostically, as it led to the discovery of the smallest of the three
      circular foci in the basodorsal left lower lobe. The form of the cryptococcosis
      among immunocompetent patients--only rarely localized in our experience--must be
      included in the differential diagnostical considerations of a circular focus in
      the lungs. In the event there are multiple circular foci with an unknown primary
      tumor, surgical intervention with a pathohistological clarification regarding a
      possible malignancy is absolutely necessary.

PMID- 9173419
TI  - [Tracheobronchomegaly--Mounier-Kuhn syndrome--case report and review of the
      literature].
AB  - Tracheobronchomegaly is a rare disorder. A marked dilatation of the trachea and
      the main stem bronchi is the characteristic sign measured as an enlarged
      transverse diameter (mean +/- 3 SD). Bronchiectasis is usual. In about one third
      of the published cases a diverticulosis was described as demonstrated in one our
      cases. For diagnostic modern radiological methods (CT including 3 D
      reconstruction, MRT) and bronchoscopy are recommended. The number and seize of
      the diverticula are documented by tracheography or by bronchography. In a part of
      all cases of tracheobronchomegaly the cause of the disorder is known. Therefore a
      division into congenital and acquired tracheobronchomegaly is useful.

PMID- 9173420
TI  - [Value of lung filter, asymmetric film-screen technique and digital storage
      screen radiography in diagnosis of coin lesion].
AB  - AIM: To evaluate the image quality of an asymmetric film-screen combination (a
      FSC), a conventional screen-film combination (FSC) at speed class 200, a lung
      filter, and digital luminescence radiograms in detecting pulmonary nodules.
      METHODS: Detail perception studies were carried out with an anthropomorphic
      phantom. The image systems were exposed under standardised conditions with 125
      kVp. The systems' perception efficiency was evaluated on the basis of 12.240
      single observations with ROC analysis. RESULTS: In the overall evaluation the a
      FSC and the filter achieved equally high assessments of 0.878 +/- 0.018 and 0.860
      +/- 0.21 respectively (p > 0.05). The 200 speed FSC and the storage phosphor
      screen radiograms did not differ significantly. In the mediastinum all the tested
      systems were clearly superior to the 200 speed FSC (p < 0.05). In the lung fields
      on the other hand the 200 speed system was given a higher assessment of 0.866 +/-
      0.026. The a-FSC had slight advantages over the lung filter and the digital
      imagining modes (p > 0.05). CONCLUSIONS: The a-FSC and digital luminescence
      radiograms provide significantly more diagnostic information in the mediastinum,
      together with high detail detectability in the lung fields and without requiring
      additional dosage.

PMID- 9173421
TI  - [Theophylline and selective phosphodiesterase inhibitor in therapy of obstructive
      respiratory tract diseases].

PMID- 9173422
TI  - [Therapy of nocturnal asthma: salmeterol versus nocturnal administration of
      retard theophylline--comparison of effectiveness and tolerance].
AB  - The aim of the present study was to compare the efficacy and the tolerability of
      salmeterol and theophylline in patients with nocturnal asthma. 16 patients were
      entered into a randomized, double-blind, crossover trial. Using a double-dummy
      technique, salmeterol (50 micrograms b.i.d. by MDI) or theophylline (Uniphyllin;
      600 mg nocte orally) were given for periods of 7 days with a wash-out period of 7
      days between treatment periods. With salmeterol the number of nights with an
      overnight fall in peak expiratory peak flow rate (PEFR) of at least 20% was
      reduced by about 20% compared to about 10% with theophyllin (p < 0.05 for the
      difference between salmeterol and theophylline). With respect to nocturnal
      symptoms 62.6% of the patients had rare or non symptoms without and 84.7% with
      salmeterol, compared to 46.5% without and 67.3% with theophylline (p < 0.05).
      With respect to the improvement of early morning symptoms, the increase of nights
      with none or rare symptoms was 46.2% with salmeterol compared to 25.8% with
      theophylline. The overall parameter of efficacy defined as a) the number of
      nights with an overnight fall in PEFR or less than 20% als well as b) none or
      rare nocturnal symptoms and c) none or rare early morning symptoms increased from
      23.4% at baseline to 75.1% during treatment with salmeterol compared to an
      increase from 24.5% at baseline with 54.8% during treatment with theophylline (p
      < 0.05). 12 patients preferred salmeterol over theophylline (p < 0.05). 3
      patients had gastrointestinal disturbances during theophylline treatment. It can
      be concluded that both salmeterol and theophylline are effective in the treatment
      of nocturnal asthma. With respect to the overall efficacy and the tolerability
      salmeterol is superior to theophylline.

PMID- 9173423
TI  - [Optical stimulation method (Snore-Stop) and tongue retainer (Snore-Master)
      without relevance in therapy of obstructive sleep apnea and snoring].
AB  - Recently intra- und extraoral devices are increasingly used in order to treat
      obstructive sleep apnea and snoring. We examined the value of an optically
      stimulating system ("eye-cover", Snore-Stop) and a tongue-retainer (Snore-Master)
      as treatment of the obstructive sleep apnoe or snoring. In case of the eye-cover
      is a microphone integrated, which detects acoustic signals (e.g. snoring). After
      detection of snoring optical stimuli are generated in front of the eyes. This is
      intended to induce an arousal of the patient, without awaking him, causing a
      change of body position and this reduces the snoring or apneas. For the
      examination of the eye-cover in 26 patients (23 men, 55.6 +/- 10.3 years)
      polygraphic studies were performed while sleeping one night with the eye-cover
      and one night without, respectively. Visual analogue scales (VAS) were used in
      order to measure quality of life and sleep and the adverse effects of the device.
      To examine the tongue-retainer 14 patients (13 men, aged 52.9 +/- 11.8 years)
      were measured polygraphically. Again the subjective scores were assessed using
      the VAS. The principle of the tongue-retainer is to create a hollow space in
      front of the teeth, in which the tongue is positioned. Fixation of the tongue in
      this ventral position is thought to enlarge the mesopharyngeal area in order to
      reduce the upper airway obstruction. For both devices the index of snoring, the
      apnea-hypopnea-index, the index of desaturation, the mean and minimal SaO2 and
      SaO2 < 90 % in % of the night did not change significantly. Furthermore the
      subjective perception of the patients concerning their quality of sleep and life
      did not change. Moreover, despite of an adequate adaptation-period the use of the
      tongue-retainer was associated with considerable adverse effects. Neither the eye
      cover nor the tongue-retainer could improve the severity of obstructive sleep
      apnoe or snoring.

PMID- 9173424
TI  - School psychologists' knowledge of children's legal rights.
AB  - School psychologists need a working knowledge of laws affecting children. This
      investigation was done to discover whether members of Ohio's school psychological
      association, including intern school psychologists who were functioning in a
      supervised capacity, are as knowledgeable about law as they need to be to avoid
      lawsuits. Participants completed a custom-designed questionnaire. Survey of
      Children's Legal Rights, including questions assessing knowledge of children's
      rights in relation to child abuse, suspension and expulsion, corporal punishment,
      rights in juvenile court, special education, freedom of religion and speech,
      search and seizure within school, divorce and child custody, school vandalism,
      and school attendance. Analysis indicated significant misconceptions about legal
      decisions; however, these school psychology practitioners have adequate legal
      knowledge about most of the surveyed themes excepting provisions for special
      education.

PMID- 9173425
TI  - [Radiologic performance in night and emergency care].
AB  - This report deals with radiologic examinations outside official working hours in
      a German university hospital and the influence of new government regulations. A
      total of 65,113 radiologic examinations were requested and performed outside
      official working hours between 1 July 1990 and 30 Juni 1994. The data were
      analyzed according to the age and sex of this patient population compared with
      the entire population studied within this 4-year period. Further analysis
      included the time of the study, the organ systems investigated, and the
      radiologic technique. About one-third of requests occurred between 16.00 and
      20.00 hours on normal working days and, thus, could be taken care of by late
      shifts. Another third covers the time between 20.00 and 08.00 hours in the
      morning, which requires inhouse staff (medical and technical). The remainder of
      the requests occurred during holidays and weekends in the daytime. The most
      common request in this analysis was for portable chest examination. About 50% of
      all portable chest examinations were performed outside regular working hours. In
      all, 17.2% of all requests involved CT and MRT studies. Government regulation did
      not change the number, technique, and frequency of radiologic examinations
      outside official working hours.

PMID- 9173426
TI  - [Invasive cervix carcinoma (pT2b-pT4a). Value of conventional and pharmacokinetic
      magnetic resonance tomography (MRI) in comparison with extensive cross sections
      and histopathologic findings].
AB  - PURPOSE: To compare staging of advanced primary cervical carcinoma (pT2b-pT4a) by
      conventional and pharmacokinetic magnetic resonance imaging (MRI) with the giant
      cross section specimen and histopathological findings. MATERIALS AND METHODS:
      Seventeen patients with biopsy-proven cancer of the cervix and clinically
      suspected invasive cancer (FIGO IIB-IVA) were prospectively examined by
      conventional (T2 and contrast-enhanced T1-weighted spin echo images) and
      pharmacokinetic MRI. All MRI findings were compared with the giant cross section
      specimen and histopathology as the standard of reference. For pharmacokinetic
      MRI, a saturation recovery TurboFLASH sequence was used with a high temporal
      resolution of 13 s per ten sections. Signal time changes were analyzed using a
      pharmacokinetic model and the computed parameter values were visualized by color
      coded overlay. RESULTS: Analysis of parametrial invasion on T2-weighted images
      resulted in an accuracy of 85% and 73% on contrast-enhanced T1-weighted images
      and on pharmacokinetic MR images respectively. Accuracy of analysis of bladder
      and/or rectal wall invasion was significantly (P < 0.05) higher on
      pharmacokinetic MR images (88%) than on T2-weighted images (67%). Contrast
      enhanced T1-weighted spin-echo images improved staging accuracy compared with T2
      weighted images (76% vs 67%). CONCLUSION: At present, conventional T2-weighted SE
      images are superior to contrast-enhanced T1-weighted SE and pharmacokinetic MR
      images in depicting infiltration of the parametrium. However, suspected
      infiltration of the bladder and/or rectum (pT4a) is diagnosed more accurately on
      pharmacokinetic images than on conventional MR images.

PMID- 9173427
TI  - [Infectious spondylitis. A retrospective evaluation of MRI markers].
AB  - AIM AND METHODS: The aim of the present study was to evaluate the MRI criteria of
      infectious spondylitis (spondylodiscitis). The MR images of 23 patients suffering
      from spondylodisitis (78% unspecific, 22% specific) were retrospectively
      analyzed. RESULTS: The height of the intervertebral discs involved was normal in
      40%, reduced in 43% and increased in 17% of the cases. The most common findings
      can be summarized in an MR triad: 1) The vertebral bodies involved are
      hypointense in T1-weighted images (100%) with a lack of delineation of the
      intervertebral discs (53%). 2) The injection of Gd-DTPA yields an enhancement of
      the vertebral bodies involved and intervertebral discs (95% and 74%
      respectively). 3) The vertebral bodies and intervertebral discs are hyperintense
      in T2-weighted sequences (76% and 90% respectively). When present, a
      paravertebral or intraspinal extension of the infection was isointense compared
      with the adjacent involved vertebral body in the majority of the patients. A
      differentiation between unspecific and specific etiology based on the MR images
      was not possible. CONCLUSIONS: The vertebral bodies affected were usually
      hypointense in T1-W with enhancement after the administration of Gd-DTPA and
      hyperintense in T2-W. The discs involved were usually hyperintense in T2-W and
      demonstrated an inhomogeneous enhancement.

PMID- 9173428
TI  - [Magnetic resonance tomography and magnetic resonance angiography in diagnosis of
      complicated popliteal artery aneurysm].
AB  - Regarding the frequency of aneurysms, the popliteal artery comes third behind the
      abdominal aorta and the iliac arteries. In up to 50% of cases a sudden limb
      threatening thrombotic occlusion may occur. Early surgical intervention is the
      therapy of choice. We report the case of a 56-year-old patient whose popliteal
      aneurysms (PAs) in both legs had been bypassed with a venous graft some years
      previously. He presented with acute pain and tumescence in the left popliteal
      fossa combined with inflammatory symptoms. Neither ultrasonography nor DSA could
      distinguish between an extravascular inflammatory process, an anastomotic
      aneurysm and a partial reperfusion of the original PA due to a leaking
      anastomosis. The correct diagnosis was provided by MRI in combination with MRA,
      confirmed by the intraoperative findings. The value of MRA in the diagnostic
      imaging of the vasculature of the lower extremities is discussed and compared
      alternative methods.

PMID- 9173429
TI  - [Temporomandibular joint morphology and morphometric findings in relation to
      degree of disk displacement. Comparative magnetic resonance tomography studies].
AB  - In order to evaluate magnetic resonance imaging (MRI) changes in correlation with
      different degrees of internal derangement of the temporomandibular joint, we
      evaluated 117 joints of 59 symptomatic patients and 31 volunteers. Data analysis
      included morphologic and morphometric characteristics. Sixteen joints (19%) were
      considered normal, 40 demonstrated anterior displacement with reduction (47%) and
      27 anterior displacement without reduction (32%). In three of the volunteers
      anterior displacement with reduction was noted. Advancing anterior position of
      the disk was associated with reduced ability to open the mouth, progressive
      deformity and shortening of the disk, thinning of the bilaminar zone, regressive
      and proliferative bony changes of the condyle, reduced translatory movement of
      the disk and condyle, thinning of joint space, cranial and dorsal displacement of
      the condyle and flattening of the slope of the tuberculum. In addition to
      alterations in condylar and disk morphology, MRI can demonstrate various
      additional measurable changes that correlate well with the degree of anterior
      disk displacement.

PMID- 9173430
TI  - [Anesthesia for magnetic resonance tomography in neonates, infants and young
      children].
AB  - INTRODUCTION: Since patient cooperation in neonates and infants up to 5 years is
      always reduced, deep sedation is usually recommended to obtain constant high
      quality images during MRI. According to the widely accepted AAP Guidelines, deep
      sedation is not always distinguishable from general anesthesia, substantiating
      the demand for state-of-the-art anaesthesia. This is particularly true in this
      age group, where pharmacokinetics and pharmacodynamics show wide interindividual
      variation. In this review we outline the techniques required to provide safe and
      effective patient care in the unique MRI environment. CHOICE OF DRUGS AND
      PROCEDURE: From the viewpoint of induction time, half-life of action and success
      rate, we have found that inhalation anesthetics and propofol present clear
      advantages. Both offer rapid induction and emergence, allowing outpatient
      examinations in a tight schedule with a reliable sedation state. Tracheal
      intubation or a laryngeal mask airway is required to supply volatile anesthetics
      and to secure the airway, since propofol in appropriate doses causes respiratory
      depression and loss of the protective reflexes. Positive-pressure ventilation is
      recommended since the reduction of tidal volumes by sedative drugs (including
      high-dose chloral hydrate, barbiturates) may cause atelectasis and decreased
      oxygen saturation. ANESTHESIA MACHINES: Several respirators work well outside a
      critical magnetic field strength of 10 mT (e.g. Draeger: Titus, Siemens: Servo
      900). The use of long low-compliance tubing (4-5 m) allows the respirator to be
      placed at the distal end of the patient table. Sidestream capnometry and
      spirometry at the proximal tube connector facilitate compensation for losses in
      tidal volume due to gas compression. Syringe pumps work properly when kept
      outside the 10 mT line. Some defibrillators (e.g., Lifepac, Physiocontrol) are
      approved for use in strong magnetic fields. MONITORING: State-of-the-art
      monitoring is also attainable for high-risk patients, including invasive pressure
      measurement. Since wiring without special filters may not cross the HF shield of
      the examination room, hydraulic and pneumatic systems are used (blood pressure by
      oscillometry, airway monitoring by side-stream spirometry). Optical fibers are
      used for pulse oximetry. A telemetric EKG is usually provided by the MRT
      manufacturer. Because oscilloscopes are distorted by the magnetic field, the
      monitors are placed outside the examination room. In addition, this eliminates
      the possibility of erasing the EPROMs contained in most monitors. PERSONNEL: With
      the setup described, the presence of a second anesthetist within the examination
      room is superfluous. A second anesthesia team can shorten the time lag between
      examinations by overlapping induction if a separate anesthesia induction and
      emergence room is provided. CONCLUSION: The level of sedation required for MRI in
      newborn and infants can only be achieved safely and efficiently by general
      anesthesia performed by trained staff. Complete state-of-the-art anesthesia care
      can be delivered if appropriate instrumentation is used.

PMID- 9173431
TI  - [Endoscopic ultrasound of pathological mediastinal findings].
AB  - INTRODUCTION: Mediastinal diseases are mostly diagnosed by CT and MRI. The
      applicability of ultrasound is limited by the surrounding air- and bone
      containing thorax, which permits only restricted echo windows. Transesophageal
      endoscopic ultrasonography circumvents this problem and ensures visualization of
      parts of the mediastinum. PATIENTS AND METHODS: We report our results in 38
      patients with pathological mediastinal findings who were examined by endoscopic
      ultrasound between 1988 and 1993. The diagnoses were established by imaging
      and/or histological procedures. RESULTS: The following mediastinal diseases were
      diagnosed in 38 patients: aberrant right subclavian artery (n = 3), right aortic
      arch (n = 1), aortic aneurysm (n = 6), cysts (n = 4), retrosternal struma (n =
      3), mediastinal lymph node tuberculosis (n = 1), Hodgkin's/non-Hodgkin's
      lymphomas (n = 11), lymph node involvement in bronchogenic carcinoma (n = 8),
      mediastinal inflammatory fibrosarcoma (n = 1). Altogether, 37/38 pathological
      findings were demonstrated endosonographically. CONCLUSIONS: The results in this
      small group of patients with pathological mediastinal findings show that
      endoscopic ultrasound can give additional information to conventional imaging
      methods. A prospective comparative study is necessary to evaluate this procedure
      in comparison to the established imaging techniques.

PMID- 9173432
TI  - [Ultrasound examination of the liver in HELLP syndrome].
AB  - A 33-year-old multiparous woman in the 34th gestational week presented with
      severe upper abdominal pain, nausea and vomiting. Clinical examination revealed
      severe epigastric tenderness. Abdominal ultrasound examination showed
      geographical areas with increased echogenicity in the right lobe of the liver.
      Through haematological examination, we found severe thrombocytopenia and
      fibrinolysis. The diagnosis of HELLP syndrome was suspected and a caesarean
      section was performed. We suggest that obstetrical patients with upper abdominal
      pain and abnormal liver sonography should immediately be haematologically
      investigated to exclude the life-threatening condition of the HELLP syndrome.

PMID- 9173433
TI  - [Severe calcifying atherosclerosis of the thoracic aorta with symptoms of aortic
      isthmus stenosis. Case report].
AB  - Calcifying obliterative atherosclerosis isolated within the descending thoracic
      aorta causing subtotal vascular occlusion was associated with symptoms such as in
      aortic coarctation in a 56-year-old patient. Remarkable in this unique case is
      the atypical and isolated manifestation of atherosclerotic disease within the
      thoracic aorta, as well as the tumorous extent of luminal calcification.
      Differential diagnostic considerations had to include calcifying tumor of the
      aorta, remnants after aortitis or secondary calcified aortic dissection.

PMID- 9173434
TI  - [Well vascularized, abdominal tumor in childhood? A CT diagnosis! Type I
      malrotation].

PMID- 9173435
TI  - [Blood disease. Extramedullary plasmacytoma with histologic confirmation by
      transthoracic biopsy].

PMID- 9173436
TI  - [Gamma knife versus stereotactic linear accelerator irradiation. Implementation,
      clinical results and cost-benefit relations].

PMID- 9173437
TI  - [Myocardial infarction--risks and procedures. Longitudinal observation of a
      population of 280,000 women and men--Project POL-MONI CA Krakow. III:
      Epidemiology and treatment of myocardial infarction].
AB  - There has been a large amount of progress in the methods of prevention and
      treatment of ischaemic heart disease (IHD), but the effect of these changes on
      mortality due to IHD has not been assessed. This paper presents the complex
      analysis of 10-year trends of incidence, case fatality and mortality due to
      myocardial infarction (MI) and changes in medical care in the acute phase of MI
      in residents of one province of Poland-Tarnobrzeg Voivodship, which was the
      target population of the POL-MONICA Krakow Project (over 280,000 men and women at
      age 25-64 years). In men, the incidence of MI, which was 335/100,000 in 1984,
      increased in 1986 to 463/1,000,000 and then was stable until 1993 when it felt to
      362/100,000. Mortality from MI, which was 149/100,000 in 1984, increased to
      212/100,000 in 1986 and then was stable until 1992, before falling to 173/100,000
      in 1993. There were large fluctuations in the incidence and mortality from MI in
      women i.e. from 58/100,000 to 116/100,000 and from 21/100,000 to 55/100,000
      respectively. In 1993 the incidence was 82/100,000 and mortality was 32/100,000.
      After adding sudden deaths and other fatal events attributed to IHD the mortality
      figures increased over the ten years of observation by an average of 29% in men
      and by 28% in women. The average total MI case fatality was 47% in men and 40% in
      women, with 86% of all deaths due to MI occurring out of hospital. Case-fatality
      of MI managed in hospital was 11% on average.

PMID- 9173438
TI  - [Myocardial infarction--risks and procedures. Longitudinal observation of a
      population of 280,000 women and men--Project POL-MONICA Krakow. I V: Prognosis of
      non-invasive treatment in myocardial infarction within 28 days since its onset].
AB  - The objective of a paper was to assess in the observational study the early
      determinants of outcome in patients with acute myocardial infarction (MI)) in one
      province of Poland (Tarnobrzeg Voivodship). The studied group were 1858
      hospitalized men and women registered in POL-MONICA Krakow study with clinical
      diagnosis of myocardial infarction or acute coronary heart disease, who fulfilled
      the criteria for definite or possible myocardial infarction according to The WHO
      MONICA Project. The main out-come measure was death before the end of 28th day
      after the onset. Patients with shock were at the highest risk to die-relative
      risk (RR) = 21.47, 95% confidence interval (CI) = 12.86-35.83. The other
      characteristics, which increased risk independently were: left ventricular
      failure (LVF) (RR = 2.51, 95% CI = 1.54-4.10) and age (RR = 1.03, 95% CI = 1.01
      1.05) per one year. Male sex and diabetes were not related to the risk of death.
      After adjustment to age, sex, shock, LVF and diabetes, lower risk was found in
      patients treated with antiplatelet agents (RR = 0.41, 95% CI = 0.29-0.59), with
      beta-blockers (RR = 0.48, 95% CI = 0.31-0.75) and with nitrates (RR = 0.62, 95%
      CI = 0.39-0.98), which were used in 66.2%, 33.1% and 97% of events respectively.
      Higher risk was found in patients treated with diuretics.

PMID- 9173439
TI  - [Phagocytic activity of blood platelets in patients infected with Giardia
      intestinalis].
AB  - Blood platelets take part in immune reactions of the organism, especially in anti
      parasitic immunity. We conducted this study measuring the phagocytic activity of
      blood platelets. The experiments were done on 35 patients infected G.
      intestinalis. Diagnosis was supported on finding trophozoits in bile cysts and
      GSA-65 protein in feces. We have found some decrease of blood platelets count and
      the increase the percentage of phagocytic platelets. Our general conclusion is,
      the parasite is able to stimulate the phagocytic activity of blood platelets.

PMID- 9173440
TI  - [Level of CA 15-3 antigen--a prognostic factor in patients with breast cancer?].
AB  - Serum CA 15-3 concentrations were determined using sandwich enzyme immunoassay in
      430 women: 214 breast cancer patients prior to any therapy, 161 patients with
      benign breast diseases, and 55 healthy controls; the cut-off limit was
      established at 30.0 U/ml. In breast cancer patients, CA 15-3 levels positively
      correlated with negative prognostic factors: higher tumor size (p < 0.001),
      positive axillary lymph nodes (p < 0.02), high histological grade (p < 0.01), low
      contents of estrogen (p < 0.05) and progesterone (p < 0.006) receptors. However
      serum CA 15-3 values raised in parallel with clinical stage of breast cancer, the
      difference was not significant. The overall diagnostic sensitivity and
      specificity of the test were 24.3% and 94.9%, respectively. The mean serum CA 15
      3 values and the percentage of positive results in breast cancer patients were
      significantly higher as compared to benign breast diseases group (27.52 +/- 27.01
      vs. 16.75 +/- 8.43, p < 0.001; 24.3% vs. 5.6%, p < 0.001, respectively) as well
      as to healthy controls (27.52 27.01 vs. 13.37 +/- 6.51, p < 0.001; 24.3% vs.
      3.6%, p < 0.01, respectively). The sensitivity of the CA 15-3 test is low and
      thus not suitable for the differential diagnosis of breast lumps. Our data
      suggest potential prognostic value of pretreatment CA 15-3 assays in breast
      cancer patients.

PMID- 9173441
TI  - [Clinical and metabolic effects of erythropoietin administration in hemodialyzed
      children].
AB  - The study aimed at the evaluation of metabolic effect of recombinant human
      erythropoietin (EPO) in children treated with repeated hemodialyses. The research
      included 16 patients aged 7-17 years of life. The observations were carried out
      for 6 months prior to and during EPO administration programme. In that time there
      were monitored changes in peripheral blood count, lean body mass, protein
      catabolic rate- pcr, urea time averaged concentration TAC and dialysis index
      KT/V. The results obtained in both phases of the investigation revealed that
      correction of anemia by means of EPO evokes in children a significant increase of
      lean body mass, while TAC decreases. The two factors combined speak for anabolic
      effect of EPO in these patients. The results of peripheral blood count obtained
      in the groups with high and acceptable exposure to uremic toxemia did not differ
      significantly, this proves that uremic toxemia does not exert inhibitory effect
      on erythropoiesis stimulated by EPO administration.

PMID- 9173442
TI  - [Experimental in vitro model of an artificial kidney--measurement of trace
      element levels using the ICP method. Preliminary studies].
AB  - Trace elements in blood serum is significantly changed in hemodialysed patients.
      The result of our experiment showed the manner and directions of the evaluated
      trace elements -Sr, Zn, Ni, Ba, B, Si, Mn and Cu movements. It was confirmed that
      reverse osmosis is efficient in the most tracers elimination, except Si, B, and
      Cu. The trace elements being present in the whole arrangement diffuse easily
      through the dialysers membrane used in our experiment, except Ni. In the membrane
      of the new, non-rinsed dialyser we detected Pb, Fe, V, Be, Ti and Al. It could
      possibly be the source of their contamination into the human organism. ICP-AES
      method of trace elements analysis reveals the possibilities of precisely, fast
      and simultaneous evaluation of big number various trace elements.

PMID- 9173443
TI  - [Functional aspects of topographic differentiation in the peritoneum].
AB  - Volumetric measurements have been performed in vitro to define permeability for
      water of different parts of peritoneum. The experiments were carried out on
      isolated fragments of rabbit mesentery, anterior abdominal wall, and diaphragm;
      mesothelial layer lining these membranes was retained in one group, whereas in
      another one it was intentionally desquamated. The membranes were mounted between
      two semichambers filled with Hanks solution; the volume on both sides of the
      membrane was strictly controlled by photo-gauges coupled with microdosi-meters.
      Transmembrane volume flow (Jv; nL/sec cm2) induced by hydrostatic pressure
      gradient (delta P; atm) was measured using an electronic device connected with
      the photo-gauges, and joined with a computer which monitored the values
      throughout the experiment. Hydraulic conductivity (Lp; in cm/sec atm) and index
      of impediment (Zp; in sec atm/cm) were calculated from the monitored values.
      Significant differences between the three types of peritoneal membrane were
      observed: the hydraulic conductivity of diaphragm was lowest, and the impediment
      highest (0.86 +/- 0.11 x 10(-2) and 116.3 +/- 12.2, respectively) contrasting
      with the corresponding values of mesentery which were highest, and lowest (38.9
      +/- 3.7 x 10(-2), and 2.57 +/- 0.25, resp.); peritoneum taken from anterior
      abdominal wall showed intermediate values (6.3 +/- 0.56 x 10(-2), and 15.9 +/-
      1.5, resp.). Removal of mesothelium induced significant increase of the
      permeability of diaphragm and anterior abdominal wall, however, no such effect
      was observed in mesentery. The obtained results seem to show that various parts
      of peritoneum may function qualitatively different during dialysis, however, any
      conclusion concerning clinical aspects of the dialysis should be drawn with all
      proper reserves.

PMID- 9173444
TI  - [Permanent catheter as an alternative vascular access for hemodialysis].
AB  - There are presented own experiences in permanent catheter application as vascular
      access for hemodialysis. During 1.5 year in 15 patients 18 catheters were
      inserted. 3 catheters had to be exchanged during first month. Catheter
      malfunctions (complete obstruction, ventil sign) were observed 13 times in 5-in
      all patients catheter patients (ratio 3.88/1000 days). Streptokinase and
      Urokinase were applied 9 times-in all patients catheter patency were reinstituted
      (however, 2 patients had insufficient blood flows). Infective complications
      (local or general) occurred 4 times in 3 patients (ratio 1.55/1000 days)-there
      were no necessity for catheter removal. On the base of own experience, as well as
      literature, there are discussed indications for permanent catheter application as
      dialysis access, practical issue in the use and complications management.

PMID- 9173445
TI  - [Pathophysiology of the harmful influence of smoking on the course of gastric and
      duodenal ulcer diseases].
AB  - Smoking increase risk of gastric and duodenal ulcer, decreases its healing rate
      and increases recurrence rate. In this report results of experiments, which aim
      was to explain mechanisms of this effect, are presented. Although the studies
      often provide conflicting results, many of them suggest that smoking potentiates
      aggressive factors (gastric acid and pepsin secretion, reflux of bile salts,
      generation of tissular aggressive factors, Helicobacter pylori infection) and
      attenuates defensive mechanism of gastric and duodenal mucosa (bicarbonates
      epidermal growth factor and gastric mucus secretion, mucosal blood flow). In this
      way smoking could disturb the balance between aggressive and defensive factors
      and predispose to peptic ulcer.

PMID- 9173446
TI  - [Iodine deficiency in the Carpathian endemic region and iodine prophylaxis in
      Southern Poland].
AB  - The improvement of the health status of the population of Southern Poland
      resulted in great extend from the introduction of table salt iodination in 1935.
      This prophylaxis caused a decrease of serious iodine deficiency disorders. Twice
      was the salt fortification process interrupted (1939-1945 and 1980-1986); and
      this brought the increase of goiter incidence in the population. Laboratory
      examinations of water and food samples coming from goiter endemic area of
      Southern Poland presented a low iodine level. The unsatisfactory clinical results
      of the iodine prophylaxis and the unstable concentration of KI in salt, force to
      correct the previous action. Apart of the epidemiological studies to be performed
      in order to establish the optimal dose of KI in table salt, the improvement of
      the iodination technique and subsequent laboratory control of KI concentration in
      salt-is urgently needed. The fortification process should be not only restricted
      to table salt, but also the industrial salt used in the food production ought to
      be iodinated. Nutrition education should be strengthen to convince the population
      to use iodized salt in household food production.

PMID- 9173447
TI  - [Clinical use of Amifostine (WR-2721) as a preparation protecting healthy tissues
      from the cytotoxic effects of chemotherapy and radiation therapy].
AB  - High doses of chemo- and radiotherapy, while theoretically more effective, are
      accompanied by severe toxicities and normal cells damage. This may have important
      implications for patients' management and can result in significant morbidity.
      Therefore, it is imperative to protect normal tissues from both the early and
      late damage caused by high doses of radiation and chemotherapy. Among the
      radioprotective agents synthetized during the last 30 years. Amifostine appeared
      to be one of the most promising. It was shown that this compound can protect
      normal cells from the toxic effects of ionizing radiation and chemotheraphy
      without affecting the efficacy of the therapy. Since 1986, initial trials with
      Amifostine in patients with diverse advanced neoplasms treated by chemotherapy
      and radiation therapy have been performed. Published data suggest that
      pretreatment with Amifostine significantly decreases hematologic, mucosal and
      renal toxicity as well as the frequency of neuropathy. Also, significant
      reduction in the frequency of hospitalization, mean hospital stay, and the number
      of days on antibiotics was observed after application of Amifostine.

PMID- 9173448
TI  - [Thrombopoietic growth factor--thrombopoietin. Molecular and biological
      properties].
AB  - Thrombopoietin (TPO) is a newly identified hematopoietic growth factor, that
      stimulates both megakaryopoiesis and thrombopoiesis through its interaction with
      a specific cell surface receptor (c-Mpl), a member of hematopoietic receptor
      superfamily, encoded by the c-mpl proto-oncogene. Recently the Janus kinases and
      STAT proteins have emerged as important elements in signaling via this family of
      receptors. The complete gene for human thrombopoietin has been cloned and mapped.
      TPO is believed to be the major physiological regulator of circulating platelet
      levels and it is hoped that this hormone will be valuable in stimulating
      megakaryocyte and platelet recovery in patients with thrombocytopenia, just as
      erythropoietin and GM-CSF or G-CSF have been valuable in stimulating the
      production of red and white cells.

PMID- 9173449
TI  - [A case of Hodgkin's disease with an uncommon clinical course. Predominant
      localization in the liver].
AB  - A 26 year old woman with systemic symptoms typical for Hodgkin's disease was
      admitted to The Oncology Clinic of the Medical Academy in Cracow in may 1988.
      Markedly elevated values of hepatic enzymes were observed. Infectious and
      autoimmune diseases were excluded. Although the diagnosis was not confirmed by
      histopathologic examination, MOPP chemotherapy was administered "exiuvantibus".
      Complete remission was obtained for two years. In 1991, when the patient relapsed
      for the second time, FNA biopsy of a hypogenic focus in the liver revealed
      Hodgkin's disease. In the sixth year of observation an enlarged supraclavicular
      lymph node appeared. Histopathologic examination of the node confirmed
      Lymphogranulomatosis-typus mixtus. The patient completed treatment in 1993 and
      since then she remains disease-free, with the overall observation period of 8
      years.

PMID- 9173450
TI  - [Fatal outcome six days following laparoscopic cholecystectomy].
AB  - The paper present a case of 45 years old woman following laparoscopic
      cholecystectomy (empyema of gall bladder) who died 6 days after operation. The
      patient were operated 16 years ago account of aortic coarctation. In the post
      operative (laparoscopic cholecystectomy) periods cardiovascular and respiratory
      complications were observed, and cured in intensive Care Department. The case of
      sudden death was massive pulmonary embolism confirmed by autopsy. The author
      think, that thrombosis came from venous vessels of pelvic or legs.

PMID- 9173451
TI  - With reference to: RAYS 21,3,1996 venous thromboembolism.

PMID- 9173452
TI  - With reference to: RAYS 21,3,1996 venous thromboembolism.

PMID- 9173453
TI  - [The 1996 National Health Conference].

PMID- 9173454
TI  - [4-month follow-up of 198 heroin addicts by general practitioners].
AB  - This study aimed to describe the short term follow-up of a cohort of 198 i.v.
      heroin users by 44 highly motivated General Practitioners (GPs). The study showed
      that for these GPs, the work-load linked with the care of these patients was
      heavy. Nearly half of them saw at least one drug-addict every day. These GPs work
      within a network and stated they benefit from a regular training on drug
      addiction topics. The profile of i.v. heroin users, followed by these GPs, is
      different from the ones usually described in other health care structures (higher
      percentage of women and better social insertion). The two main motives to consult
      a GP are the demand of drugs concerning their addiction and medical concern (due
      to infectious diseases especially). The answer of GPs, concerning the demand of
      drugs, divide physicians into two groups: those who never prescribe morphine like
      drugs as substitution and those who do so. In addition, both of them often
      prescribe psychotropic drugs to some of their patients. Nevertheless, these
      prescriptions are just one of the elements of a follow-up contract between a GP
      and his patients. Morphine like prescription is more frequently described among
      long term drug-addicts already well-known by GPs. This selection prohibits a
      straight comparison of the results of two groups of patients (with and without
      morphine like substitution). But the main fact is that patients under morphine
      like substitution are followed better (in terms of continuity) after 4 months of
      observation.

PMID- 9173455
TI  - [Epidemiology of suicide attempts in Reunion Island].
AB  - In order to specify the epidemiological characteristics of attempted suicides on
      Reunion island, a quantitative study was carried out, using Emergency Room
      registers of all the hospitals on the island. This enabled collection of 9526
      files. The results revealed a high proportion of suicide attempts
      (335/100,000/year), particularly prevalent in rural areas to the south of the
      island. There was a tendency towards over representation of women, though less
      distinct than in Europe, as well as an abnormally frequent use of pesticides or
      herbicides. Medication and violent means were not used as often as in France.
      These outcomes, in particular the very high frequency (especially in the rural
      areas of the south), along with the significance of medico-psychological factors,
      should be taken into account by anthropologists, linguists, clinical specialists,
      in order to help determine preventive measures.

PMID- 9173456
TI  - [Children of the GAZEL Cohort: I--Prevalence of contacts with the medico
      educational system for psychological reasons, and associated factors].
AB  - An epidemiological survey of French children aged 4 to 16 was conducted in order
      to estimate the 12-months rates of service utilization for psychological reasons
      and to assess the factors associated with service use in this community sample. A
      large sample of 2582 children and adolescents was recruited from the families
      whose one parent was employed by the national electricity and gaz company (EDF
      GDF). Of these employees, 20,000 have volunteered for a long-term prospective
      cohort study of their health and, since 1989, they have participated to annual
      surveys and additional ad hoc research programmes. Families with a child aged 4
      to 16 in 1991 were selected. Only one child was selected in each family, and the
      sample was stratified by socio-economic status and family size according to
      census data. A survey questionnaire comprising a valid measure of child
      psychopathology (Child Behavior Checklist: CBCL) and an additional questionnaire
      including questions related to service use was used as a means of data
      collection. The response rate was 62.2% and factors associated with participation
      in the survey were analysed. The 12-months prevalence rate of contact for
      psychological motives were: 42.3% for general practitioners and family doctors,
      7.8% for speech and language therapists, 9.5% for educational specialists, and
      6.0% for mental health professionals. With the exception of general
      practitioners, rates of service contact were significantly higher for boys.
      Logistic regression analysis was used to identify separately factors associated
      with recent contact for each category of professionals. Results showed that, for
      all professionals, high scores on the CBCL measure was significantly associated
      with service use, the strongest association being found for mental health
      professionals. Family structure was also predictive of the latter, with higher
      rates of contacts for those children living in families whose parents are
      divorced, separated or widowed. Some differences for contacts with doctors were
      found according to the region; otherwise, no effects of socio-economic status,
      educational level of the parent, or other socio-economic indicators were found to
      predict service utilization. The implications for services are discussed.

PMID- 9173457
TI  - [Development of a job-exposure matrix in the heavy-metal industry in France].
AB  - A job exposure matrix (JEM) was developed by a committee of experts using the
      DELPHI method, in the French hard metal industry, in order to assess occupational
      exposures to cobalt along with tungsten carbide resulting from the industrial
      process. This JEM is part of a nested case-control study, carried out within the
      historical cohort of workers ever employed in these factories, aimed at assessing
      lung cancer risk. The committee included 8 experts: hygienists, chemical
      engineers, occupational physicians and epidemiologists. The JEM was developed in
      four stages: (i) visit of factories, (ii) definition of lines (job-periods) and
      columns (exposures) of the JEM, (iii) definition of coding procedures, (iv)
      coding the cells of the JEM. This last stage used a method derived from the
      DELPHI method. Throughout the study period 1945-1994. 320 job-periods and 21
      agents were defined. A quantitative assignment (level 0 to level 9) along with a
      frequency code (1 to 3) was attempted for 4 agents, whereas only a qualitative
      assignment (non exposed/exposed, i.e. 0/l) was done for the other agents. An
      additional probability code (1 to 3) was assigned to all agents. This procedure
      led to 46 columns and 14,720 cells in the JEM. When applying the DELPHI method,
      the consensus of the committee was obtained for 85% of all cells after the first
      individual assignment of experts, 88% after the second individual assignment and
      100% after the third assignment by the experts all together. In order to validate
      the JEM, these expert assignments will be brought together with the results of
      exposure measurements that were performed in some workplaces of these factories.
      The JEM will also be linked with the data base of the case-control study for the
      exposure assessment of cases and controls.

PMID- 9173458
TI  - [Relationship between preoperative delay in hip fractures, postoperative
      complications and risk of death].
AB  - The objective was to describe the relationship between preoperative delay,
      postoperative complications, and risk of death at 6 months. The population is
      constituted of 200 subjects aged 65 years or older who were living at home and
      treated for a hip fracture in any of three of Quebec's hospitals between April,
      1st, 1987 and March, 31, 1989. Chi-square or F-test, and linear and logistic
      regression were used to test the relationship between the variables. Preoperative
      delays varied from 2 to 403 h (median, 45 h). Variations between hospitals were
      particularly important; median delay at hospital 1 was 109 h, at hospital 2, 36
      h, at hospital 3, 30.5 h. Only 5% of the variance of the delay was explained by
      the subjects' characteristics before the fracture. The relationships between
      delay and postoperative complications are not significant. However, the risk of
      death at 6 months increased with the length of operative delay; the observed
      increase tends to be linear (p = 0.03). These results suggest first, that surgery
      for hip fracture had to be consider as an urgency, second, that it could be done
      36 hours or less after the arrival at hospital.

PMID- 9173459
TI  - [Cost-effectiveness study of 2 long-term home oxygen therapy management systems].
AB  - In France, home oxygen therapy for patients with chronic obstructive pulmonary
      disease (COPD) is carried out by nonprofit associations (NP) or profit-making
      health organisations (PM). In a retrospective pragmatic approach we analysed the
      costs and the effectiveness of these 2 types of structures delivering oxygen at
      home. Between July 1985 and March 1994, 234 patients were involved in the
      survival study (chosen as an effectiveness indicator), 24% in PM and 76% in NP.
      The economic appraisal was performed, from the insurer's point of view, on a
      representative sample of 61 patients and analysed in detail all the ambulatory
      costs for respiratory care. Patient survival was similar in both types of
      structures (Cox model). Oxygen therapy represented the largest share of the total
      ambulatory cost (81.6% in PM and 72.1% in NP). The NP structures were less costly
      for reasons linked to their preference for concentrator (p = 0.004 in a Wilcoxon
      test), all the other direct costs being non-statistically different. NP
      structures had a significant influence on a low level of ambulatory costs
      (adjusted OR = 10.98, p = 0.0004) in logistic regression. As oxygen treatment
      plays an important role in the variation of costs, further pragmatic studies
      should help to better understand what are the real motivations to choose one mode
      of oxygen administration more than an other and should determine factors that may
      sometimes lead physicians not to comply with clinical guidelines (actually a
      quarter of the patients did not have a PaO2 < 60 mmHg).

PMID- 9173460
TI  - [Respiratory disorders during sleep].
AB  - Sleep-disordered breathing includes snoring, upper airway resistance syndrome,
      sleep hypopneas and apneas, and is a borderline pathology between several
      disciplines (neurology, pneumology, cardiology, oto-rhino-laryngology, etc.). The
      common element is an abnormal increase in upper airway resistance during sleep.
      In mild cases, this increase accelerates airflow and induces vibrations of the
      pharyngeal structures (snoring); in severe cases the airway is occluded and
      airflow ceases (obstructive apnea). Sleep apnea syndrome (SAS) is present in 4%
      of males and 2% females in the general population. The risk factors are an age
      above 50, male sex, weight excess, presence of respiratory symptoms, tobacco
      smoking, alcohol consumption, use of hypnotic drugs... Snoring is much more
      frequent than sleep apnea, present in up to 50% of males aged 50 yr or more; most
      snorers do not have apneas ("simple" snorers). Apneas end with a micro-arousal;
      this sleep disruption explains the excess daytime sleepiness of patients with
      SAS. The daytime sleepiness is responsible for the increased rate of accidents
      (traffic, domestic, work...) in SAS patients. The second effect of apneas is
      desaturation, leading to heart rhythm abnormalities, coronary or cerebrovascular
      accidents, pulmonary vasoconstriction, systemic hypertension, etc. Screening for
      SAS is justified by its prevalence, by the potentially severe consequences and by
      the existence of an efficacious treatment: continuous positive airway pressure.

PMID- 9173461
TI  - [Statistic tests concerning population mortality indicators].
AB  - The objective of this note is to present simple statistical tests applied to
      common comparison problems met in descriptive studies in the general population.
      These tests apply to classical mortality indicators: crude and specific death
      rates, standardized rates (direct and indirect methods). The tests are based on
      the convergence of the Poisson distribution towards the normal distribution. For
      each type of comparison, confidence intervals are also provided.

PMID- 9173462
TI  - [Informal and professional assistance in persons aged 75 years and over].

PMID- 9173463
TI  - [Dissemination of mortality indicators usable at the local level (I).
      Surveillance network of medical causes of death in health services of French
      cities].

PMID- 9173464
TI  - [Relationship between unemployment and mortality rate].

PMID- 9173465
TI  - [50-60 Hz electromagnetic fields and cancer risk].

PMID- 9173466
TI  - [Treatment of rheumatoid arthritis: leave the pyramids to the Egyptians?].

PMID- 9173467
TI  - [Physiopathology, clinical aspects and prevention of renal insufficiency caused
      by contrast media].
AB  - Contrast-media associated nephropathy (CMAN) consists in a sudden impairment of
      glomerular filtration rate following exposure to radiographic contrast materials.
      Damage may be limited to an asymptomatic mild increase of blood creatinine, or
      reach the highest levels of nitrogen retention compatible with acute renal
      failure. Some preexisting clinical conditions or pathologies may lead to CMAN:
      not only renal insufficiency, diabetes mellitus, multiple myeloma, congestive
      heart failure and severe hypertension, but also simple dehydration and a growing
      series of immunologic diseases are recognized as predisposing condition. The
      exact mechanism responsible for renal injury is still doubtful but recently
      animal models have shown substantial ischemic changes that may be added to the
      traditional presumed pathogenesis of direct tubular toxicity and intra-tubular
      obstruction. As renal ischemia stimulates both endogenous vasoconstrictor and
      vasodilator substances, it is now supposed that CMAN acts similarly to non
      steroidal anti-inflammatory agents, selectively inhibiting the vasodilatory
      prostaglandin phase and therefore causing a derangement of the physiologic
      vasoconstriction/vasodilatation balance of renal circulation. The role of oxygen
      free radicals to contribute to renal dysfunction is considered. Low osmolality
      non ionic contrast media when compared to conventional high osmolality ionic
      contrast media have reduced but not eliminated CMAN. Simple but effective lines
      of prevention include the previous selection of patients predisposed to CMAN for
      concomitant pathology, suspension of FANS or any other recognized nephrotoxic
      substance, the least amount of contrast media compatible with radiologic
      visualization of the patient's problem, careful hydration of the patient before
      contrast injection and sustained diuresis afterwards. The usefulness of pre
      treatment with Ca-channel blockers or atrial natriuretic factors remains sub
      judice.

PMID- 9173468
TI  - [Study of spontaneous resolution of bronchial spasm after methacholine challenge.
      Comparison of patients with different degree of hyperreactivity].
AB  - The study was designed to assess the spontaneous recovery of bronchial spasm
      induced by methacholine in bronchial challenge tests and to examine the
      mechanisms and the modalities involved as well as the influence of dosage. The
      phenomenon was analysed in 32 hyperreactive patients diagnosed as asthmatics by
      measuring FEV1 as soon as maximum bronchial constriction (PD20) had been achieved
      and after 5, 10, 15, 30 and 60 minutes. The data obtained were subjected to
      variance analysis. Results show: 1) as regards duration of spontaneous recovery,
      that FEV1 returned to pre-challenge levels after 60 minutes in both the severely
      and moderately hyperreactive patients; 2) as regards onset of regression, that
      onset depended on the level of sensitivity, occurring after 30 minutes in the
      severely affected, after 15 minutes in the mild cases; 3) as regards recovery
      intensity, that in the moderated cases the recovery was more pronounced in the
      first 15 minutes than subsequently. Data show that the onset and intensity of the
      spontaneous recovery change according to the degree of sensitivity. That might
      reflect a greater affinity and/or bonding of methacholine in the muscarinic
      receptors of the severely affected, but the possibility of a difference in
      mediator metabolization speed cannot be excluded. In conclusion, research into
      the recovery of bronchial spasm may contribute to a better understanding of
      bronchial hypersensitivity and provide new information of value on the diagnosis,
      pathogenesis and treatment of the condition.

PMID- 9173470
TI  - [Monoclonal antibody therapy].
AB  - Monoclonal antibodies (mAb) are antibodies, produced by cell clones, directed
      against specific antigens (Ag), which act by binding specifically to the target
      Ag. Depending on the mAb used, this binding may have different effects on the
      target (neutralizing, lytic, opsonizing or antibody dependent cytotoxicity,
      ADCC). In clinical practice, mAb are used as immunosuppressants, antineoplastic
      agents, or for diagnostic purposes. mAb are given i.v. by slow infusion; the
      dosage depends on the mAb used. Contraindications include allergic, neoplastic,
      infective diseases, but also hypertension, cardiac failure and pregnancy.
      Infusions are usually well tolerated, headache and skin rashes being recorded
      only rarely; however, little is known about long-term effects (possible
      derangement of the immune response and/or increase in neoplasms). mAb are
      potentially a powerful tool in medicine, but more studies are required to define
      their role and establish their possible adverse effects in humans.

PMID- 9173469
TI  - [2 cases of acute cholestasis caused by ticlopidine].
AB  - We report the case of two patients suffered from cholestatic jaundice occurred 3
      4 weeks after starting ticlopidine therapy. In both cases the diagnosis was made
      by ruling out any other known cause of acute hepatitis or cholestasis. One
      patient underwent liver biopsy, which showed a typical intralobular cholestatic
      pattern and a slight lymphocytic infiltration of the portal tracts. The other
      patient, a 29 year-old woman, was taking ticlopidine as the sole drug, further to
      an ischemic stroke occurred while she was taking oral contraceptives; she
      presented a diffuse itchy dermatitis, fever and slight eosinophilia besides
      cholestasis. In both patients ticlopidine was discontinued and liver tests
      returned to normal values within 4-8 weeks; no rechallenge was attempted and
      ticlopidine was replaced with another antiplatelet drug. To the best of our
      knowledge 19 cases of ticlopidine-related cholestatic disease have been described
      so far in the literature. Its pathogenesis is still unknown, although some
      clinical findings and experimental results from patients with acute enteropathy
      or agranulocytosis induced by ticlopidine suggest that the drug may act through a
      toxic mechanism, perhaps mediated by prostaglandins.

PMID- 9173471
TI  - [New possible pathways for melanogenesis: opiomelanins].
AB  - Opioid peptides and other Tyr-NH2-terminal peptides are substrates in vitro for
      mushroom and sepia tyrosinase giving rise to synthetic melanins retaining the
      peptide moiety (opiomelanins). The melanopeptides are characterized by a total
      solubility in hydrophilic solvents at neutral and basic pH. Opioid peptides
      (enkephalins, endorphins, esorphins), if oxidized by tyrosinase in the presence
      of Dopa are easily incorporated into Dopa-melanin, producing mixed-type pigments
      which can also be solubilized in hydrophilic solvents. Melanins deriving from
      opioid peptides exhibit paramagnetism as evidenced by an EPR spectrum identical
      to that of Dopa-melanin. However the presence of the linked peptide chain is able
      to influence dramatically the electron transfer properties and the oxidizing
      behaviour of the melanopeptides, so that whereas Tyr-Gly-melanin appears to
      behave as Dopa-melanin, Enk-melanin does not exhibit any oxidizing activity.
      Opiomelanins are characterized by a peculiar UV-VIS spectrum i.e. by the presence
      of a well distinct peak (330 nm) disappearing upon chemical treatment by acid
      hydrolysis. Opiomelanins are stable pigments at neutral and basic pH in the dark,
      whereas H2O2 addition leads to a 15% degradation. Under simulated solar
      illumination opiomelanins are more easily destroyed with respect to Dopa-melanin
      with increasing degradation of exposed to increased hydrogen peroxide
      concentrations and more alkaline pH. Some speculations on the possible existence
      and role of opiomelanins have been outlined.

PMID- 9173472
TI  - [Intestinal permeability].
AB  - Intestinal mucosa has an absorptive function and acts also as a selective barrier
      against potential antigenic, toxic and carcinogenic substances. Intestinal
      permeability can be defined as the capacity of mucosal surface to be penetrate by
      specific substances through unmediated diffusion. There are two theories about
      molecular permeation routes: the first one hypothesizes a transcellular (through
      small pores), a paracellular (through big channels) and a lipophilic pathways;
      the second one gives a key role only to paracellular tight-junctions. In many
      diseases we can find changes in intestinal permeability evaluable by simple and
      non invasive tests, administering "per os" probe molecules. These substances
      cross the epithelium in different way and amount according to their
      physicochemical features and mucosal integrity; then they reach circulation and
      are eliminated in urines where they can be detected. The most frequently
      molecules used are mono/disaccharides, 51Cr-labelled ethylenediaminetetraacetate
      (51Cr-EDTA) and polyethylene glycol (PEG). This simple method has become more and
      more used for diagnostic and speculative aims. These intestinal permeability
      tests have a low specificity so they cannot be used for a definitive diagnosis of
      intestinal disease; nevertheless, the high sensitivity for intestinal mucosal
      damage could make them a necessary method to evaluate mucosal integrity after
      therapy, to select patients with a specific symptoms and to support, particularly
      in pediatric populations, more specific and invasive diagnostic tests.

PMID- 9173473
TI  - [Agranulocytosis during a treatment with terbinafine].

PMID- 9173475
TI  - [Energy expenditure in man].

PMID- 9173474
TI  - [Hepatic involvement and hemolytic anemia disclosing adult onset Still disease].

PMID- 9173476
TI  - [A case of myocardial rupture in closed thoracic injury].

PMID- 9173477
TI  - ["Bridge to transplantation" using the Pierce-Donachy pulsatile ventricular
      assist device (Thoratec)].

PMID- 9173478
TI  - [How I explore... a patient with orthostatic hypotension].

PMID- 9173479
TI  - [Pharma Clinics. Drug of the month. Benzamycin, an up-date on topical treatment
      of acne].

PMID- 9173480
TI  - [Pharma Clinics. Metallic inhalation chamber for the young asthmatic child: the
      Kidspacer].

PMID- 9173481
TI  - [Image of the month. Pearly penile papules or viral condylomas].

PMID- 9173482
TI  - [How I treat... facial melasma].

PMID- 9173483
TI  - [Clinical case of the month. Uremic pericarditis in a dialysed patient].

PMID- 9173484
TI  - [Therapeutic efficacy of cultured keratocytes combined with autograft patches for
      the cicatrization of leg ulcers].

PMID- 9173485
TI  - [Therapeutic indications for breast cancer].

PMID- 9173486
TI  - ["Supraconservative" surgery of infraclinical breast lesions].

PMID- 9173487
TI  - [Up-to-date treatment of breast cancer. Myeloblastic chemotherapy and
      hematopoietic cell grafting].

PMID- 9173488
TI  - [Support in the after care of patients operated for breast cancer].

PMID- 9173489
TI  - [Migraine: genetic, physiopathological, and therapeutic innovations].

PMID- 9173490
TI  - [The value of trans-hysteroscopic electroresection in the treatment of benign
      organic uterine bleeding. Comparison with classical surgical techniques].

PMID- 9173491
TI  - [Hepatic complications of chemotherapy. From trivial cytolysis to hepatic veno
      occlusive disease].

PMID- 9173493
TI  - [What is your diagnosis? Eisenmenger reaction in long-term ventricular septal
      defect].

PMID- 9173492
TI  - [Ocular manifestations of AIDS. Personal observations and literature review].

PMID- 9173494
TI  - [Current aspects in the pathogenesis of acute pancreatitis].
AB  - Alcohol abuse and gallstones are the most important factors in the pathogenesis
      of acute pancreatitis. Other factors are less frequent, and in some patients one
      is unable to identify any risk factor. Even in the most frequent forms of
      alcoholic or biliary pancreatitis little is known about the cellular and
      molecular mechanisms which lead to severe pancreatitis. New experimental studies
      have shown that many biochemical and morphological events are similar in
      different experimental models of pancreatitis as well as in human disease. These
      changes include intracellular premature activation of trypsin, blockade of
      luminal enzyme secretion and appearance of intracellular vacuoles. Although
      activated trypsin triggers the activation of other proteases, it is not trypsin
      but other proteases (e.g. elastase, chymotrypsin and phospholipase) which damage
      the pancreatic acinar cell. These pathogenetic findings may lead to the
      development of inhibitors which more effectively inhibit the latter cell-toxic
      proteases and may thereby help to improve the therapy.

PMID- 9173495
TI  - [Clinical aspects and classification of acute pancreatitis].
AB  - Clinically acute pancreatitis is characterized by severe abdominal pain and
      systemic symptoms, such as nausea, vomiting and circulatory shock. In most cases
      the diagnosis is verified, and differential diagnoses are excluded, by elevated
      serum enzyme activities as well as characteristic findings in imaging procedures.
      The mild form of acute pancreatitis (about 80%) is characterized by an
      uncomplicated course and recovery within 72 hours in response to adequate
      therapy. By contrast, severe pancreatitis (about 20%) shows formation of necroses
      and a protracted course which frequently is dominated by development of systemic
      complications with subsequent failure of individual or several organ systems. On
      this background, early discrimination between mild and severe pancreatitis is
      important for therapeutic management and assessment of prognosis. Several
      classifications have been suggested in recent years but their use has been
      limited because they partly depend on complicated multiscoring systems. On the
      other hand, it has been possible to establish simple severity markers such as
      serum CRP and PMN-elastase that correlate well with further clinical course and
      outcome.

PMID- 9173496
TI  - [Diagnosis and differential diagnosis of pancreatic carcinoma].
AB  - Despite improved imaging procedures for diagnosis, there is no improvement in
      prognosis of pancreatic carcinoma. This may be explained by the lack of early
      symptoms and the aggressiveness of the tumor with its tendency of early
      metastasis. However, in most cases imaging procedures enable an exact
      preoperative diagnosis and a reliable preoperative staging. Unnecessary
      laparotomies are avoided since resectability can be correctly predicted in more
      than 80%. Transabdominal sonography and computed tomography are mandatory in
      almost all cases. Endoscopic retrograde cholangiopancreatography has not lost its
      importance due to the possibilities of transpapillary biopsy or brush-cytology. A
      major role for ERCP is palliative therapy of cholestasis by stenting of malignant
      bile duct stenosis. At present endosonography can be regarded as most sensitive
      procedure to detect small pancreatic tumors and as a very reliable method for
      preoperative T-staging. Detection of mutations of the Ki-ras gene in shedded
      cells of pancreatic secretions may improve the still difficult differential
      diagnosis chronic pancreatitis versus pancreatic carcinoma.

PMID- 9173497
TI  - [Pancreatitis/pancreatic carcinoma--value of diagnostic procedures: ERCP and
      cytology].

PMID- 9173498
TI  - [Systemic sclerosis].

PMID- 9173499
TI  - [Thoracoscopy. A tremendous progress for patients, a permanent challenge for
      thoracic surgeons].

PMID- 9173500
TI  - [Varices of the lower limbs and surgery: current problems].

PMID- 9173501
TI  - [Reconstructive surgery in chronic venous disease of the lower limbs].

PMID- 9173502
TI  - [Current possibilities for endoluminal arterial vascular procedures].

PMID- 9173503
TI  - [Arterial surgery in complicated reconstruction].

PMID- 9173504
TI  - [Role of lymphadenectomy in the surgical treatment of tumors].
AB  - In addition to the excision of the tumor itself, the surgical management of
      carcinomas includes the removal of regional lymph nodes or lymphadenectomy. The
      lymphatic system is not the only path of metastatic spread but it is often the
      main one. The percentage of tumors with lymph node metastases varies with the
      location and above all with the extent of the tumor at the time of surgery. For
      example, axillary metastases are much less frequent in cancers discovered by
      screening mammography than in those with clinical signs. Lymphadenectomy is
      important for loco-regional control and to determine the prognosis which may
      dictate adjuvant therapy. In some patients, it also contributes to the cure of
      their disease by removing lymph nodes metastases that sometimes can only be
      detected by immunohistochemistry. Lymphadenectomy should be very extensive when
      done with curative intent and very selective when performed only for prognostic
      information.

PMID- 9173505
TI  - [Surgical treatment of pulmonary metastases].

PMID- 9173506
TI  - [Adenoma and neuroendocrine carcinoma: 2 adjacent intestinal neoplasias. Simple
      coincidence? Report of 2 cases].

PMID- 9173507
TI  - [Gastric leiomyoblastoma: literature review and report of a case].
AB  - Leiomyoblastoma is a rare, smooth muscle tumor of the stomach that occurs chiefly
      in the antrum. We present the case of a 51 year old man suffering from asthenia
      and mild upper abdominal pain. Investigations showed a big exculcerated tumor of
      the lesser gastric curvature. He underwent a subtotal gastrectomy for a non
      metastasizing leiomyoblastoma, grade 1. But already 5 months later, he developed
      an invasive non-resectable local recurrence of high grade malignancy and died 3
      month after a second look. Those tumors affect middle-aged patients who present
      usually upper gastrointestinal bleeding or peptic ulcer-like symptoms. Although
      the large majority of leiomyoblastoma are benign, malignancy occurs in up to 10%
      of cases. A large surgical resection of the tumor (including the total thickness
      of the gastric wall) or a partial gastrectomy is recommended.

PMID- 9173509
TI  - [Insertion of permanent perfusion systems for chemotherapy. A ray of hope for the
      patients].
AB  - The number of patients undergoing chemotherapy for tumor disease has considerably
      increased in the last years. One of the problems of these long-term treatment
      modalities is the destruction of the peripheral venous system due to the repeated
      venous punctures for the therapy itself as well as for the laboratory analyses.
      This has been the motive for the research on permanent perfusion systems which
      would work at long term in a reliable way. Nowadays, several industrial products
      are available, devices for the standard implantation intravenously but also
      devices for intraarterial and intraperitoneal use. In our hands, the access
      through the subclavian vein with the end of the catheter in the superior caval
      vein has proven to be a safe and easy method. The port is placed in the triangle
      between the coracoid process and the clavicula. The large experience made by the
      centers in Basle and Berne as well as our own experiences in Bienne have clearly
      demonstrated the benefit of these systems for the patient. Nevertheless, some
      complications have to be mentioned such as the wellknown complications of the
      puncture of the subclavian vein. The risk of complete occlusion of the catheter
      must be expected at the rate of 0.5%. Hematomas immediately after the punction of
      the port have also been described. We would like to outline that complications of
      these permanent infusion systems are rare, especially in comparison with the
      complication rate of the normal percutaneous central venous sets. We therefore
      strongly advocate the implantation of these devices in the first instance before
      the beginning of any treatment in order to save the peripheral venous system of
      these patients.

PMID- 9173508
TI  - [The importance of adjuvant chemotherapy in the treatment of colonic carcinoma:
      SAKK Study 40/93 (Swiss Work Group for Clinical Cancer Research)].

PMID- 9173510
TI  - [Minimally invasive surgery or celioscopy; is it surgery of the future or for
      today?].

PMID- 9173511
TI  - [Laparoscopic treatment of colovesical fistulas. Our experience with 11 cases].

PMID- 9173512
TI  - [Evaluation of 102 inguinal hernias treated with transperitoneal laparoscopy].

PMID- 9173513
TI  - Quality of life in gastrointestinal disease: a challenge and/or panacea?
      Proceedings of a workshop. Cape Town, South Africa, 3-4 November 1995.

PMID- 9173514
TI  - [Solidarity in science. The Cerec anniversary celebration in the courtyard of the
      University of Zurich-Irchel on 15 March 1996].

PMID- 9173515
TI  - [Cerec--an undisputed success of tooth-color CAD/CIM restorations. The Scientific
      Cerec Symposium of 15/16 March 1996 in Zurich].

PMID- 9173516
TI  - [Polycythemia caused by liver carcinoma in cattle and sheep].
AB  - Polycythemia associated with hepatic carcinoma was diagnosed in a 10-year-old
      cow, an 8-month-old heifer and a 3-year-old sheep. The cow was referred to our
      clinic because of weight loss, reduced appetite, hematuria, marked reddening of
      the mucosa of the tear canal, oral cavity and vestibule and an increased
      hematocrit. Clinical examination also revealed injected scleral vessels. The
      erythrocyte count, the PCV, hemoglobin concentration and the activities of the
      hepatic enzymes were increased. Ultrasonographic examination revealed a very
      large liver with a focal echogenic lesion. Based on all findings, a diagnosis of
      polycythemia associated with a liver tumor, was made. The cow was slaughtered.
      Multifocal liver tumors were diagnosed histologically as hepatocellular
      carcinoma. The heifer and sheep had similar clinical and hematological findings.
      Hepatocellular carcinoma was diagnosed in the heifer and cholangiocellular
      carcinoma in the sheep. It was concluded that in all three patients, polycythemia
      was caused by hepatic carcinoma.

PMID- 9173517
TI  - [Epidemiologic studies of the occurrence of bovine virus diarrhea/mucosal disease
      in 2892 cattle in 95 dairy farms].
AB  - Blood samples were collected from 2892 cows and heifers of various ages from 95
      dairy farms in the Kanton of St. Gallen and were tested for antibodies against
      bovine virus diarrhea. The percentages of seropositive, seronegative and
      inconclusive cases were 83.7%, 13.0% and 3.3%, respectively. In all herds, at
      least one case was seropositive, and in 29% of the herds, all the animals tested
      were seropositive. On a herd basis, the seroprevalence ranged from 16.2% to 100%
      with a mean (+/- SD) of 85.8 +/- 17.6%. The seroprevalence in one to two-year-old
      heifers was not significantly different from that of the entire sample.

PMID- 9173518
TI  - [Von Willebrand factor concentrations in blood plasma of Bernese mountain dogs].
AB  - Many Bernese Mountain dogs have been found to exhibit an increased hemorrhagic
      tendency of unknown etiology. Since other bleeding disorders have been excluded
      by routine tests and Bernese Mountain dogs have been listed to have von
      Willebrand's disease (vWD), we analyzed the plasma concentration of the von
      Willebrand Factor (vWF) in 160 Bernese Mountain dogs that were used for breeding
      in Switzerland in 1992. We also evaluated the suitability of the commercial
      Asserachrom vWF test kit to quantitate vWF in canine plasma by comparing the
      plasma vWF determination with validated vWF ELISA test. The vWF plasma
      concentration in Bernese Mountain dogs ranged from 13% to 162%, with the
      Asserachrom test kit (normal range 67% to 124%). Similar values were obtained
      with the research vWF ELISA kit (10% to 166%), and there was a close correlation
      between the two test methods. In 8 of the 9 Bernese Mountain dogs with initially
      low vWF concentration (< 60%), the determination was repeated on another sample.
      Since the values were well within the normal range, a problem with the collection
      of blood for the first determination is suspected. We conclude that vWD does not
      appear to be a clinical issue in Bernese Mountain dogs in Switzerland and is,
      therefore, not likely to be the cause of the observed bleeding tendency. The
      commercially available Asserachrom vWF test kit seems suitable for the
      determination of canine vWF plasma concentrations. It is recommended that low vWF
      values will be confirmed by the determination in second samples.

PMID- 9173519
TI  - [Hip dysplasia in dogs--a new radiologic technique for the recognition of loose
      hip joints].

PMID- 9173520
TI  - [Contrast in ultrasound diagnosis].

PMID- 9173521
TI  - [Doppler examination of the fetal left and right pulmonary artery. Relation to
      fetal position and gestational age: a methodological study].
AB  - A Methodical Study: AIM OF THE STUDY: To analyse the feasibility of colour and
      spectral Doppler assessment of blood flow in the fetal right (RPA) and left (LPA)
      main pulmonary arteries in relation to fetal position and to gestational age.
      STUDY DESIGN: The fetal position was a priori divided into 3 types, depending on
      whether the fetal heart was visualised apically (Type 1), from the right side
      (Type 2) or from the left side (Type 3). Three groups A (19-25 weeks gestation),
      B (26-32) and C (33-39) including 33 consecutive pregnancies each, were examined
      to document the fetal position as well as the rate of the successful Doppler
      examinations of the RPA and/or LPA. RESULTS: The fetal position Type 2 was most
      common throughout gestation (in group A = 42%, B = 36%, C = 51%) followed by the
      type 3 and then type 1. The rate of successful Doppler records from the RPA and
      LPA depended on the fetal position: In Type 2 RPA in 98%; in Type 3, LPA in 100%;
      but the apical approach was not effective (< 40%). Depending on gestational age,
      the success rates for a Doppler examination of at least one vessel were high (>
      85%), whereas successful examination of both vessels was unlikely (12%).
      CONCLUSIONS: In the second half of pregnancy, independent of fetal position,
      Doppler examination of at least one pulmonary artery is successful in most cases,
      whereas the assessment of both vessels is rather difficult.

PMID- 9173522
TI  - [Accuracy of ultrasound weight assessment--comparison of vertex vs. breech
      presentation].
AB  - AIM: To determine the quality of prenatal sonographic weight estimation,
      comparing breech and vertex presentations. METHOD: In 147 breech presentations
      (BP) and 149 vertex presentations (VP), the biparietal head diameter (BPD), the
      fronto-occipital head diameter (FOD) and the transverse abdominal diameter (ATD)
      were measured. From these data, the weight was estimated, using Shepard's formula
      before 28 weeks and Hansmann's thereafter, and compared to the delivery weight.
      Both formula were modified to incorporate the virtual BPD (vBPD), derived from
      the BPD, FOD and the calculated head circumference. In the BP group, the role of
      examiner skills was evaluated, comparing the accuracy of experienced (DEGUM II
      qualifications) and average individuals. RESULTS: The accuracy for BP was nearly
      identical to that for VP (= 0.915 vs. = 0.929). The examiners' qualifications had
      a detectable but not significant influence on the results (= 0.942 vs. = 0.892).
      CONCLUSION: Ultrasound measurements yield comparable results in both BP and VP,
      if the vBPD is used. In our opinion, ultrasonic weight estimation is a useful
      adjunct when determining the manner of delivery in BP.

PMID- 9173523
TI  - [Ultrasound assessment of ovarian tumors--comparison between transvaginal 3D
      technique and conventional 2-dimensional vaginal ultrasonography].
AB  - DEFINITION: Three-dimensional (3D) ultrasound is capable of visualising all three
      orthogonal planes simultaneously. With the stored volumetric data, imaging planes
      can be reconstructed that are not visible when using standard vaginosonographic
      procedures. AIMS OF THE STUDY: In patients with ovarian tumours, diagnosis and
      the appropriate therapeutic approach depend to a crucial degree upon the results
      of sonographic investigations, which therefore need very exact diagnostic data.
      Two-dimensional (2D) vaginosonography can only yield sagittal and frontal
      sections of the lesser pelvis; 3D volume scanning, however, visualises all three
      perpendicular planes simultaneously on a monitor screen. In cystic tumours of the
      ovary, conspicuous parietal structures can be specifically localised and rendered
      three-dimensionally in the surface mode. Such imaging capabilities create new
      perspectives in assessing ovarian tumours. METHOD: Within the framework of a
      prospective study at the Gynecological Clinic of the University of Mainz, we
      compared the sonographic findings obtained for 45 patients with ovarian tumours
      using 2D and 3D vaginosonography. After the transvaginal application of
      conventional 2D vaginosonography, the tumours were examined by means of 3D
      sonography. RESULTS: The use of 3D volume scanning was advantageous because we
      could image specifically targeted planes and reconstruct image planes that cannot
      be shown using standard vaginosonography. In addition, the volumetric technique
      allows 3D surface reconstruction of conspicuous parietal structures from a wide
      variety of different perspectives. These advantages allow one to better assess
      the grading of tumours especially of those that are cystic. Problems associated
      with the application of this transvaginal 3D technique module orientation within
      a given volume, the overlapping of sonographic planes, increase the time required
      for surface calculations and increased data storage capacity. CONCLUSION:
      Transvaginal 3D sonography represents a new technique of imaging. Owing to its
      ability to register all three imaging planes simultaneously as well as to
      visualise surfaces three-dimensionally, this technique opens up new
      sonomorphologic possibilities in the evaluation of ovarian tumours.

PMID- 9173524
TI  - [Radiologic versus ultrasound fallopian tube imaging. Painfulness of the
      examination and diagnostic reliability of hysterosalpingography and
      hysterosalpingo-contrast-ultrasonography with echovist 200].
AB  - Evaluation of tubal patency is usually assessed with hysterosalpingography (HSG)
      or laparoscopy including chromopertubation. Sonographical visualisation with
      Echovist 200 (hysterosalpingo-contrast sonography-HyCoSy) provides a new
      noninvasive tool. Therefore we conducted a prospective controlled study to
      compare sonographic and radiological evaluation of the fallopian tube. Main test
      parameters were accuracy of both methods and patient discomfort. PATIENTS AND
      METHODS: 50 patients were enrolled in this study. All patients were examined by
      both techniques; the sequence was randomly chosen. The results of HSG and HyCoSy
      were compared. Patient discomfort was assessed with a standardised questionnaire
      using a visual analog scale (0-10). RESULTS: Diagnosis of tubal patency
      identifying proximal or distal blockage was the primary end point using HSG as
      standard technique. Proximal and distal patency by HSG was sonographically
      confirmed in 82.9% (63/76) and 82.1% (46/56) tubes respectively. If HSG revealed
      proximal or distal occlusion, identical results were obtained in 91.7% (22/24) or
      60% (12/20) by HyCoSy. No significant differences were found in patient
      discomfort. However a significant correlation was demonstrated between tubal
      patency and discomfort. The lowest score was obtained in patients with open tubes
      (4.6) increased in patients with distal occlusion (6.0) and reached a maximum
      with proximal pathology (8.7). CONCLUSION: Compared to conventional HSG, HyCoSy
      provides a highly efficient evaluation of tubal pathology and can be successfully
      used as a noninvasive screening method.

PMID- 9173525
TI  - [Periportal hyperechogenicity of the liver. Clinical aspects and pathology of the
      so-called fixed star heaven phenomenon of the liver].
AB  - INTRODUCTION: The clinical significance of the sonographic finding "periportal
      hyperechogenicity", which is characterized by hard periportal echoes, is largely
      undetermined. This phenomenon has been reported in a large number of disorders,
      as well as in healthy persons. METHODS: A prospective study of 1853 patients
      revealed this finding in 12 cases. These 12 patients were followed up after two
      to four months. RESULTS: Only four cases were seen to still have diffuse
      periportal accentuation in the follow-up, while five patients showed a partially
      and three a completely normal liver. The laboratory values of these 12 patients
      were largely normal at the time of diagnosis and follow-up. Periportal
      accentuation was not correlated with any hepatological disorders. Examination
      using two different ultrasound devices revealed no major differences. DISCUSSION:
      Overall, these findings confirm the earlier assumption that this sonographic
      picture designated as periportal hyperechogenicity or accentuation is not
      diagnostic of any hepatological disorder, nor is it even a sign of disease,
      because most patients with this phenomenon can be termed hepatologically
      "healthy".

PMID- 9173526
TI  - [Ultrasound in diagnosis of traumatic intra-abdominal lesions. Value in primary
      diagnosis in the shock unit].
AB  - AIM: To evaluate sonography as a tool for initial diagnosis in emergency room
      patients with abdominal trauma. METHOD: 174 cases of abdominal trauma were
      selected from 1837 emergency care patients. The initial sonographic findings were
      compared to CT-evaluation, operative and autopsy results, and both clinical and
      sonographic follow-up. RESULTS: In 31 cases initial sonographic findings were
      positive, leading to 6 laparotomies. In another 6 cases, changes of follow-up
      sonographic testing led to laparotomy. In 143 patients, the initial sonographic
      evaluation was negative. In this group, follow-up evaluation revealed changes in
      16 cases leading to 3 laparotomies. In 8 patients with stab injuries, the
      negative sonographic study was confirmed by operative findings. CONCLUSION:
      Sonography is a well-tested diagnostic method in evaluating patients with
      abdominal trauma. Follow-up examinations-even with negative initial results-are
      needed. While the time interval between evaluations depends on the individual
      risk factors, hourly reevaluation is generally appropriate.

PMID- 9173527
TI  - [Vaginal ultrasound in perityphlitic abscess].
AB  - A 21 year-old woman presented with an encapsulated mass involving the right
      ovary, tube and caecum. On transvaginal sonography a 15 mm-target structure was
      surrounded by irregular, echo-poor formations suggestive of an inflamed appendix
      and a perityphlitic abscess. Transvaginal sonography is of diagnostic value in
      differentiating an appendiceal abscess from a right-sided tubo-ovarian abscess.

PMID- 9173528
TI  - [Adnexal torsion with hemorrhagic infarct in early pregnancy. Diagnosis by color
      coded vaginal Doppler sonography].
AB  - A 25 year-old woman presented with left lower quadrant pain in the 11th week of
      gestation. Transvaginal sonography showed a 7 x 8 x 5 cm cystic-solid mass with
      an adjacent 9 mm echogenic structure on the left side corresponding to the
      adnexal stalk. Color Doppler sonography revealed the absence of central or
      peripheral flow within the mass suggestive of adnexal torsion and subsequent
      infarction. Laparoscopic detorsion of the left adnexa was not followed by
      restoration of perfusion ad a left adnexectomy was performed. Transvaginal color
      Doppler sonography is useful for preoperative diagnosis of adnexal torsion.

PMID- 9173529
TI  - [Cost effective media in vaginal ultrasound uterus and fallopian tube diagnosis].
AB  - AIM: The recent development of hysterocontrastsonography (HyCoSy) for assessing
      tubal patency may provide an alternative to current methods, which are either
      invasive (laparoscopy and dye) or involve exposure to radiation and require a
      radiology department (hysterosalpingography). METHOD: Following the introduction
      of an intrauterine balloon catheter, the contrast agent (Echovist) is slowly
      injected into the cavity and tracked using ultrasound as it passes through the
      tubes. The technique is well tolerated as an outpatient method, and takes about
      15 to 20 minutes to perform. RESULTS: In a clinical trial with infertile women we
      compared the results of HyCoSy to laparoscopy and dye. In 90 out of 108 tubes
      investigated the results agreed-equivalent to a sensitivity of 88% and a
      specificity of 82%. Three false negative findings on the one hand and 15 false
      positive findings on the other represent a negative predictive value of 96% and a
      positive predictive value of 58%. In approximately 50% of patients, this
      outpatient procedure caused little or no pain, and in 40%, moderate pain. Only a
      small part of the investigated group (8%) complained about serious discomfort; in
      two cases (3%) the procedure was discontinued because of pain. CONCLUSION: HyCoSy
      is a reliable and simple method to provide preliminary information about tubal
      patency. It may be carried out at an early stage of the algorithm to investigate
      the infertile couple, and may so lead to more rapid and efficient treatment.

PMID- 9173530
TI  - Diabetes project.

PMID- 9173531
TI  - Biology department splits.

PMID- 9173532
TI  - Honeybee thermoregulation.

PMID- 9173533
TI  - Honeybee thermoregulation.

PMID- 9173534
TI  - Ethics of AZT studies in poorer countries attacked.

PMID- 9173535
TI  - A catalog of cancer genes at the click of a mouse.

PMID- 9173536
TI  - Chemists explore the power of one.

PMID- 9173537
TI  - New clues found to circadian clocks--including mammals'.

PMID- 9173538
TI  - Malaria research. How the parasite gets its food.

PMID- 9173539
TI  - Morphologists learn to live with molecular upstarts.

PMID- 9173540
TI  - Stretching single protein molecules: titin is a weird spring.

PMID- 9173541
TI  - A new face for the endoplasmic reticulum: RNA localization.

PMID- 9173542
TI  - As time PASses: the first mammalian clock gene.

PMID- 9173543
TI  - Engineering chemical reactivity on cell surfaces through oligosaccharide
      biosynthesis.
AB  - Cell surface oligosaccharides can be engineered to display unusual functional
      groups for the selective chemical remodeling of cell surfaces. An unnatural
      derivative of N-acetyl-mannosamine, which has a ketone group, was converted to
      the corresponding sialic acid and incorporated into cell surface oligosaccharides
      metabolically, resulting in the cell surface display of ketone groups. The ketone
      group on the cell surface can then be covalently ligated under physiological
      conditions with molecules carrying a complementary reactive functional group such
      as the hydrazide. Cell surface reactions of this kind should prove useful in the
      introduction of new recognition epitopes, such as peptides, oligosaccharides, or
      small organic molecules, onto cell surfaces and in the subsequent modulation of
      cell-cell or cell-small molecule binding events. The versatility of this
      technology was demonstrated by an example of selective drug delivery. Cells were
      decorated with biotin through selective conjugation to ketone groups, and
      selectively killed in the presence of a ricin A chain-avidin conjugate.

PMID- 9173544
TI  - On raising energy expenditure in ob/ob mice.

PMID- 9173545
TI  - [Malignant bone tumors].
AB  - Owing to advances in adjuvant therapy, the outlook for patients with primary
      malignant bone tumors has improved dramatically in recent decades. This applies
      both to improved survival and to increased limb salvage rates. The diagnostic
      strategies and a staging system for malignant bone tumors are outlined. Technical
      aspects of the standard limb salvage procedures, such as Tikhoff-Linberg
      resection at the shoulder, internal hemipelvectomy, proximal and distal femur
      resection and rotation plasty are presented. The use of soft tissue procedures
      such as flaps and the use of modular implant systems has reduced the complication
      rates of limb salvage procedures. In the future we hope to further improve
      prognosis and quality of life for such patients by the application of risk
      adapted strategies for chemotherapy and surgery.

PMID- 9173546
TI  - [MRI arthrography--improved diagnosis of shoulder joint instability].
AB  - In a prospective study, we examined 34 patients with shoulder instabilities and 5
      patients with unclear chronic shoulder pain (4 females, 35 males; 18-56 years of
      age, median 28 years) by CT arthrography and MRT arthrography from August 1994
      through December 1995. No complications were seen when gadolinium-DPTA was
      applied intra-articularly. Twenty-three patients were followed up by operation
      and/or arthroscopy; 20 patients underwent a modified, open Bankart operation. In
      this paper, we present a new classification for damage of the anterior capsule
      and labrum. MRT arthrography showed better results in judging the anterior labrum
      and in determining the degree of damage to the labrum (sensitivity, specificity
      and accuracy 100%) in comparison with CT arthrography (sensitivity 90%,
      specificity 100%, accuracy 91%). Furthermore, MRT arthrography gave clearer
      results than CT arthrography regarding SLAP and cartilage lesions. Thus, MRT
      arthrography has proved to be a very exact method for diagnosing shoulder
      instabilities and is superior to CT arthrography in diagnostic accuracy.

PMID- 9173547
TI  - [Results of reconstruction of acromioclavicular joint rupture with PDS implants].
AB  - From 1986 to 1994, we treated 79 patients with acute acromioclavicular
      separations by surgical reconstruction. According to the classification of
      Rockwood and Matsen. 65 patients had type III lesions, 1 patients had a type IV
      lesion and 13 patients had type V lesions. Both the coracoclavicular ligaments
      and the ligaments of the acromioclavicular joint were reconstructed. An
      additional ligamentous augmentation was performed using completely resorbable 5-
      and 10-mm polydioxanone-sulphate bands. Fifty-five patients (70%) were reexamined
      1-7.5 years after surgery (mean 28 months). The results were good to excellent in
      50 cases (90%). Fifty-two patients (93%) achieved a range of motion with an
      abduction deficit of less than 20 degrees. Calcifications in the area of the
      coracoclavicular ligaments did not affect the final range of motion. Early
      complications consisted of a subcutaneous infection, one deep infection, and one
      reconstruction failure. Late complications consisted of a redislocation in 2
      patients and symptomatic post-traumatic arthritis of the joint in 3 cases.
      Augmenting the reconstruction with polydioxyanone-sulphate bands allowed early
      functional post-operative treatment. With this procedure, patients do not require
      removal of the implant, and complications from breakage or migration of metal
      implants are avoided.

PMID- 9173548
TI  - [Sports and work capacity after stabilization of recurrent shoulder joint
      dislocations].
AB  - Eighty-one patients (83 shoulder joints) underwent surgical procedures for
      recurrent shoulder joint dislocations. All patients had an extra-articular
      osteotomy with subcapital derotation according to Weber's technique. In all, 46%
      of the patients underwent additional intra-articular reconstructions. After a
      mean follow-up of 4.6 years, redislocations (6%) were observed only when a
      singular derotation technique had been used. Complications were minor (2.4%).
      External rotation of the operated shoulder joints was normal in most patients
      with a mean of 48.5 degrees. Improvement in sporting activities was seen in 80%
      and in working activities in 70%. The mean Constantscore was 89.2. Subacromial
      pain was rare and correlated with reduced scores in functional strain tests
      postoperatively. There was no postoperative arthritis owing to the derotation
      technique. Because of unrestricted rotation and early functional therapy, we
      observed a good indication for an additional derotation technique when a Hill
      Sachs defect is evident.

PMID- 9173549
TI  - [Long-term results of therapy of open and closed fractures of the elbow joint].
AB  - Fractures of the elbow joint are quite rare compared with the total incidence of
      injuries to the extremities. However, elbow fractures often result in significant
      disability. Therefore in a retrospective study, we have evaluated criteria that
      are of prognostic value for late functional outcome. Sixty-four (10.3%) of 622
      patients with closed elbow fractures and 107 (89%) of 119 patients with open
      elbow fractures underwent a physical examination. The mean follow-up time was 8.2
      years. The functional outcome was recorded by a modified score (0-max. 15)
      according to Morrey. Epidemiological data from both groups revealed a greater
      severity and higher degree of injury in open fractures than in closed fractures.
      In contrast, both groups presented a comparably good functional result. The most
      significant factor for poor outcome (score < 5) was identified as nerve lesions.
      Among all nerve lesions in open fractures, 45% resulted in a functional score of
      < 5; in 42% of closed fractures combined with a nerve lesion a similarly poor
      result was also noted. A second major factor appeared to be the method of primary
      therapy. An external joint transfixation resulted in a score of < 5 in 32% of
      patients that were treated primarily by transfixation. In cases initially treated
      with open reduction and internal fixation, only 18.5% of open fractures and 3.1%
      of closed fractures presented a similar low score. According to our results the
      late functional outcome of elbow fractures depends less on the type of fracture
      than on the presence of a nerve lesion and the method of primary treatment, which
      should facilitate early mobilization.

PMID- 9173550
TI  - [Value of MRI in assessment of cruciate ligament replacement].
AB  - To evaluate the predictive value of MRI in the early postoperative course after
      cruciate ligament replacement, a prospective study was performed. Twenty patients
      with reconstructed anterior and/or posterior cruciate ligament were examined
      clinically and with contrast-enhanced MRI 2, 12, 24 weeks, 1 and 2 years
      postoperatively. The clinical examinations were evaluated according to the scores
      by Lysholm, OAK and IKDC. The MRI scans (SP 63, 1.5 Tesla) were evaluated
      regarding the quality and signal intensity of the reconstructed ligament. During
      the first postoperative year a significant increase in signal intensity and
      inhomogeneity of the neoligament in MRI was observed in 16 patients with an
      average value for signal/noise of 1.1 2 weeks postoperatively up to 6.9 1 year
      postoperatively. In 12 patients the reconstructed ligament could not be evaluated
      in the 1-year postoperative MRI, whereas none of these patients was suspected
      clinically of having instability. In the 2-year postoperative MRI, the signal
      intensity of the neoligament was found to be decreasing again with improvement in
      judgement.

PMID- 9173551
TI  - [Modification of proprioceptive ability of knee joints with primary
      gonarthrosis].
AB  - In the study presented, knee joint proprioception of 17 patients with primary
      degenerative joint disease of the knee joint was evaluated. As a control group,
      the proprioception of 30 healthy volunteers with clinical and anamnestically
      inconspicuous knee joints was examined. We tested the proprioceptive capability
      of the subjects with an angle reproduction test. Additionally, all knee joints
      were measured with and without an elastic knee bandage. The study showed
      significantly more deterioration in knee joint proprioception in patients with
      gonarthrosis than in the control group. Even the proprioception of the
      contralateral, healthy knee joint was worse than the results of the control
      group. However, after using an elastic knee bandage, significant improvement in
      the proprioceptive abilities of the injured knee joint was documented.

PMID- 9173553
TI  - [Fracture management in polytrauma. Timing and tactics].

PMID- 9173552
TI  - [Treatment outcome after complex pelvic trauma in children].
AB  - Between 1972 and 1994 21 children up to 14 years old sustained complex pelvic
      trauma treated at the Trauma Department of the Hannover Medical School. Sixteen
      of the 17 survivors were followed at an average of 8.9 years. In 8 patients
      operative treatment of the disrupted pelvic ring (external or internal fixation)
      was performed; in 8 patients the treatment was conservative. At follow-up 9
      patients (56%) were pain-free; 4 reported slight, 2 moderate and one patient
      severe pain (at rest). There were no neurological deficits. Four patients had
      disturbed micturia, and 1 had bowel incontinence. Radiological evaluation showed
      anatomic reconstruction of the pelvic ring in 9 cases (56%). Residual maximum
      displacement of 12 mm was detected in 2 patients. In 3 cases osteoarthritis or
      ancylosis of the SI joint was present. In 3 cases a clinically not disturbing
      heterotopic ossification was found. Another 2 cases had ossifications of the
      pubic symphyses. A post-traumatic acetabular dysplasia was detected in 2 cases; a
      hypoplasia of the hemipelvis was seen in 3 patients. In a retrospective analysis
      of the primary radiographs, 13 pelvic lesions were not detected during the
      primary clinical course (sacral fractures, lesions of the triradiate cartilage).
      Despite this finding the pelvic outcome was rated good and excellent in 10
      patients (63%), moderate in 1 patient (hypoplasia of the hemipelvis, and poor in
      5 patients (31%) with severe pain or urogenital disturbances. The maximum ratings
      in social reintegration was given to 9 patients, a medium rating to 7 patients.
      All patients were socially integrated.

PMID- 9173554
TI  - [Right-sided diaphragmatic rupture with intrathoracic displacement of the entire
      right lobe of the liver].
AB  - A case of rupture of the right hemidiaphragm resulting from blunt trauma with
      complete intrathoracic dislocation of the right hepatic lobe in a multiple trauma
      patient is presented. After a primary chest X-ray study had been interpreted as
      showing right-sided hemothorax, the thoracic drainage tube was accidentally
      placed into the liver. CT revealed a diagnosis of diaphragmatic rupture with
      intrathoracic liver dislocation. The liver was replaced and the extended dorsal
      diaphragmatic rupture was closed primarily via an abdominal approach. Problems of
      diagnosis and operative procedure in rare cases of fresh right-sided blunt
      traumatic diaphragmatic ruptures are discussed. CT may be helpful in the
      differential diagnosis of pulmonary contusions, hemothorax and diaphragmatic
      disruptions with intrathoracic herniation of intra-abdominal organs.

PMID- 9173555
TI  - [Alveolar cell adenoma of the lung].

PMID- 9173556
TI  - [Krukenberg tumor: a clinical case report].

PMID- 9173557
TI  - [Pseudomembranous colitis].

PMID- 9173558
TI  - [1996 literature review: imaging the intestines].

PMID- 9173560
TI  - [Diagnosis of the female urethra and examination technique with Doppler balloon
      urethrography].

PMID- 9173559
TI  - [Focal nodular hyperplasia].

PMID- 9173561
TI  - [1996 review of the literature: liver imaging].

PMID- 9173562
TI  - [Anxiety-induced reactions in connection with magnetic resonance tomography (MRI)
      examinations].

PMID- 9173563
TI  - [Conventional pelvis-leg arteriography with iomeprol 400. Does higher
      concentration contrast medium have a diagnostic advantage?].

PMID- 9173564
TI  - Curriculum development for the rural specialist.

PMID- 9173565
TI  - [The clinico-endoscopic, psychological and physical characteristics of duodenal
      peptic ulcer patients using piracetam and aevit].
AB  - Clinical efficacy of piracetam and polyvitamin agent aevit was studied in
      recurrence of duodenal ulcer. When added to standard antiulcer therapy, piracetam
      and aevit result in early regression of duodenal ulcer clinical and endoscopic
      manifestations, correction of psychopathic reactions and increased exercise
      tolerance.

PMID- 9173566
TI  - [Gastric and duodenal mucosal function in peptic ulcer patients exposed to
      endoscopic laser therapy and sanatorium-health resort factors].
AB  - A comparative study of gastric and duodenal bulb mucosa has been performed in 138
      patients with ulcer before and after treatment. The patients were treated with
      either He-Ne laser or copper steam laser alone vs combination of laser therapy
      with spa treatment. The most favourable was the complex including green spectrum
      laser in combination with administration of Shira Lake mineral water and
      electrophoresis of this water.

PMID- 9173567
TI  - [The role of antitumor drugs in treating stomach cancer patients].
AB  - The treatment of advanced gastric carcinoma is a challenge to oncologists. Within
      the last 6-7 years several new regimens have been introduced: EAP, FAMTX, MEP,
      MVP, ELF. Overall response rate of these schemes is 30-40%, a complete response
      seldom reaching 10%. Anticancer drugs significantly improve quality of life.
      Chemotherapy of advanced cancer is the method of choice. New combinations and
      regimens may appear promising.

PMID- 9173568
TI  - [The morphometric and immunohistochemical indices of the gastric and duodenal
      mucosa in the dynamic treatment of erosive gastroduodenitis in those who worked
      in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric
      Power Station in the follow-up period].
AB  - 62 Chernobyl wreckers with erosive gastroduodenitis (50 cases) and ulcer (12
      cases) were admitted to hospital where they received standard drugs and local He
      Ne laser treatment of erosions and ulcer located in the antral stomach and
      duodenal bulb. Histological, bacterioscopic, morphometric and immunohistochemical
      examinations have identified chronic inflammation and disturbance of local
      immunity. After treatment epithelialization of erosions was not accompanied by
      normalization of morphometric and immunohistochemical parameters. This suggests a
      high risk of recurrences.

PMID- 9173569
TI  - [The characteristics of the clinical manifestations of cardiospasm at different
      stages].

PMID- 9173570
TI  - [The clinical significance of the liver glutathione system in chronic lesions].
AB  - It is shown that chronic hepatobiliary pathology is associated with a fall in
      spontaneous metabolite conjugation related to reduced concentration of hepatic
      glutathione. There was also enhanced activity of glutathione-dependent enzymes.
      This indicates progress of compensatory processes associated with mobilization of
      detoxication phase 2, i.e. stimulation of conjugation processes under depression
      of cytochrome P-450 system. The authors ascertain high informative value of
      hepatic glutathione transferase in assessment of disease activity in patients
      with chronic active hepatitis and hepatic cirrhosis.

PMID- 9173571
TI  - [Chronic cholecystitis--some lithogenic aspects].
AB  - A total of 100 patients were examined: 35 patients with biliary dyskinesia, 44
      patients with chronic acalculous cholecystitis, 21 patients with chronic
      calculous cholecystitis. The patients were evaluated clinically with
      investigation of motor-evacuation function of the gall-bladder, activity of
      inflammation in the gall-bladder, bile lithogenicity, morphofunctional
      characteristics of the stomach APUD-cells and degree of Helicobacter pylori
      contamination. Chronic calculous cholecystitis is characterized by clearcut
      symptoms, hypomotor dyskinesia, high cholesterol, signs of diffuse atrophic
      gastritis. Chronic acalculous cholecystitis with hypomotor dyskinesia was
      accompanied by mild intoxication, presence of C-reactive protein, high
      cholesterol, diffuse atrophic gastritis.

PMID- 9173572
TI  - [The prevalence and structure of biliary tract diseases in the rural population
      of northern regions of Siberia].
AB  - Biliary tracts were investigated in 3420 migrants and 1445 aborigines (Evens,
      Evenkis) living in Evenkia and Yakutia. Acalculous chronic cholecystitis and
      cholelithiasis were found in 8.5 and 8.8% of the migrants, respectively. In
      aborigines these diseases occurred in 4.5 and 1.5%, respectively. The risk to
      develop biliary disease for migrants grows after 4-5 years of stay in the Far
      North. It is concluded that biliary pathology in the Far North population was
      related to ethnic and geographical factors.

PMID- 9173573
TI  - [The diagnostic and therapeutic significance of thrombocyte functional activity
      and the factors in its regulation in chronic diseases of the large intestine].
AB  - To elucidate diagnostic value of platelet functional activity in chronic colon
      disease, we studied ADP-induced platelet aggregation (PA, in vitro) and cAMP
      concentration in blood plasma. If patients had chronic catarrhal, ulcerative
      colitis or chronic colon stasis, their serum cAMP appeared low, while initial
      rate of ADP-induced PA was high. The above alterations varied with the disease
      severity, in exacerbation and remission. CAMP, histamine and epinephrine were
      tried as regulators of platelet activity. Phosphodiesterase inhibitor trental
      proved efficient in the treatment of chronic colon diseases. It has improved
      clinical condition of the patients, inhibited the initial rate of ADP-induced PA,
      secured its partial or complete reversibility through a rise in plasma and
      platelet cAMP concentrations.

PMID- 9173574
TI  - [Initial experience in the diagnosis of thrombophilia due to activated protein C
      resistance].
AB  - The authors describe the first in Russia cases of thrombophilia caused by factor
      Va resistance to activated protein C. This abnormality was diagnosed in 6 of 25
      patients (24%) with recurrent early thrombosis. The diagnosis was conducted
      according to a modified method implying the addition of protac (activator of
      protein C) to normal platelet poor plasma (PPP) free of factor V containing 100%
      of protein C. Protac dose was adjusted to increase the activated partial
      thromboplastin time (APTT) 2.4-2.8-fold in mixing PPP of the examinee with plasma
      containing activated protein C. The indices were estimated indicative of
      insufficient prolongation of APTT in response to activated protein C. Of 6
      patients, 2 had apparent and 4 strong resistance to activated protein C.
      Treatment policy in this variant of thrombophilia is discussed.

PMID- 9173575
TI  - [Lymphogranulomatosis: a systems analysis of the age- and sex-related
      characteristics of hemopoiesis and metabolism].
AB  - 72 clinical and laboratory features were analyzed on the IBM PC 486 for 126 new
      cases of lymphogranulomatosis prior to treatment. Myelograms were found to vary
      with sex and age of the patients demonstrating close relations between
      hemopoiesis and processes in the lymph nodes. In males maturation of myeloid
      elements KM was inhibited, though they had more monocytes KM. These monocytes got
      more numerous in unfavorable histological variants and generalization.
      Lymphopenia and monocytosis were more pronounced in patients under 30 becoming
      more severe in generalization and intoxication. Age-related changes in
      cholesterol in lymphogranulomatosis patients were abnormal: in older patients
      cholesterol was low. This phenomenon is extremely unfavorable. The findings
      elucidate prognostic value of sex and age in lymphogranulomatosis and suggest a
      hypothesis that monocytes (macrophages) and secreted by them monokines are
      responsible for specific intoxication, neutrophilia and lymphopenia. Berezovsky
      Sternberg cells may be hybrids of macrophages and B-lymphocytes.

PMID- 9173576
TI  - [Toxic complications of high-dose polychemotherapy in the transplantation of bone
      marrow and of peripheral blood stem cells].
AB  - The authors propose their own system of assessment of high-dose polychemotherapy
      toxicity. The system was applied to toxic complications of high-dose
      polychemotherapy in 31 patients with hematological malignancies subjected to
      allogenic, autologous bone marrow transplantation and transplantation of stem
      cells from peripheral blood within the scope of different protocols of high-dose
      polychemotherapy in conditioning regimen. A special scale developed in the
      Belarus Center for Bone Marrow Transplantation basing on the above system
      provides prediction of survival in early post-transplantation period.

PMID- 9173577
TI  - [The problems of present-day enterology].

PMID- 9173578
TI  - [Rheumatoid arthritis and multiple myeloma--the risk of a combination of the 2
      diseases].

PMID- 9173579
TI  - [A comparative evaluation of local therapy methods in treating osteoarthrosis
      deformans].
AB  - 71 patients with knee joint osteoarthritis deformans in exacerbation with weak
      exudative component have received outpatient treatment: intrajoint injections of
      kenalog with novocaine, jet intra- and periarticular injections of the above
      drugs, magnetolaser therapy (groups 1, 2 and 3, respectively). The response was
      obtained in 85, 90 and 75%, respectively. Neither toxicity nor complications were
      recorded. The above methods are recommended for use in outpatient departments and
      clinics.

PMID- 9173580
TI  - [The effect of fluvastatin (Lescol) treatment on the clinical status and function
      of the liver in patients with ischemic heart disease].
AB  - The study included 30 IHD patients with primary hypercholesterolemia (22 males
      and 8 females). 18 and 12 patients have received a single daily dose of
      fluvastatin 20 and 40 mg, respectively, in the evening for 12 weeks. The drug
      effect was assessed by changes in the clinical status, lipid spectrum, transport
      metabolic and absorption-secretory functions of the liver. IHD patients with
      hypercholesterolemia were found to have dysfunction of the hepatobiliary system.
      Fluvastatin treatment reduced the level of total cholesterol (Ch), LDLP Ch,
      triglycerides. HDLP Ch levels remained unchanged. Atherogenic lipoproteins
      aggregation diminished. Positive changes occurred in hepatic metabolism:
      bilirubin concentrations lowered, serum albumin went up, absorption-secretory
      function of hepatocytes normalized, hepatic mono-oxidase system activated.
      Fluvastatin-related hepatic damage was not reported in the course of 12-month
      follow-up.

PMID- 9173581
TI  - [The characteristics of the peripheral blood monocytes in diabetics].
AB  - The study was aimed at laboratory evaluation of monocytes in peripheral blood of
      patients with insulin-dependent and non-insulin-dependent diabetes mellitus.
      Irrespective of the disease type and clinical features, monocytes count at the
      expense of Fc-positive monocytes was increased, activity of monocytes in the test
      NBT reduction was inhibited. The problem of monocyte involvement in diabetic
      angiopathy genesis and the role of insulin in this process are discussed. The
      findings justify introduction of immunomodulating therapy of diabetes mellitus
      patients with drugs acting on monocytes.

PMID- 9173582
TI  - [Ulfamid in the combined therapy of gastric and duodenal peptic ulcer].

PMID- 9173583
TI  - [A case of the successful use of plasmapheresis in the combined treatment of a
      female patient with autoimmune agranulocytosis against a background of Schmidt's
      syndrome].

PMID- 9173584
TI  - [A rare variant of multifocal fibrosis].

PMID- 9173585
TI  - [A case of the successful use of protein A adsorption in a patient with acute
      kidney failure in rapidly progressing lupus glomerulonephritis].

PMID- 9173586
TI  - [The irritable bowel syndrome (its clinical picture, diagnosis and treatment)].

PMID- 9173587
TI  - [The outlook for gene therapy in cardiology].

PMID- 9173588
TI  - [The enterosorbent polifepan in the treatment of organic diseases of the
      digestive system].

PMID- 9173589
TI  - [The white-coat hypertension syndrome].

PMID- 9173590
TI  - [New developments in the treatment of bronchial asthma: leukotriene inhibitors].

PMID- 9173591
TI  - [2 cases of cryptococcosis in cats].
AB  - In two cats, a Persian and a D.S.H. cat, cutaneous Cryptococcosis is described.
      No signs of involvement of other organ systems nor underlying causes were
      established. One cat seemed refractory to ketoconazole-therapy. In both cats the
      skin lesions disappeared within 2-3 months itraconazole treatment. Latex
      agglutination tests against Cryptococci capsula antigen were performed and stayed
      longtime elevated while clinical lesions were not present anymore. The test may
      give an indication about prognosis.

PMID- 9173592
TI  - [How the Similia principle of homeopathy resolved an emergency].

PMID- 9173593
TI  - [How the Similia principle of homeopathy resolved an emergency].

PMID- 9173594
TI  - [How the Similia principle of homeopathy resolved an emergency].

PMID- 9173595
TI  - [The Veterinary Disciplinary Tribunal].

PMID- 9173596
TI  - [Hyperadrenocorticism in ferrets].

PMID- 9173597
TI  - [Food irradiation with ionizing radiation; an overview].
AB  - Irradiation of food in the Netherlands may only be performed by a company that
      works according to the (Dutch) law on nuclear energy. Irradiation is used to
      reduce the number of pathogenic and spoilage micro-organisms in food. Thus the
      use of preservatives can be diminished. The use of this technique for the
      decontamination of food is sustained by the FAO/WHO. Codex Alimentarius Committee
      and other organisations like the Dutch Public Health Council. It should be
      accepted world wide and used in every country. Irradiation of food is at the
      moment allowed in 38 countries and practically performed in 28 countries. Gamma
      radiation from the cobalt-60 isotope is the commonly used source of radiation.
      The treatment causes in most foodstuffs no organoleptic changes. On the other
      hand, organoleptic deteriorations provoked by micro-organisms rest unchanged by
      the treatment. An inferior lot can not be 'irradiated' into an impeccable food.
      In the Netherlands it is only allowed to irradiate foodstuffs mentioned in the
      (Dutch) Irradiated Food Products Act which-is part of the (Dutch) Food and
      Commodities Act.

PMID- 9173598
TI  - [Healing 'in spite of or thanks to the therapy'].

PMID- 9173599
TI  - [Pioneers: veterinarians from earlier times (20). Jean-Baptiste Huzard (1755
      1838)].

PMID- 9173600
TI  - [Screening for deafness in companion animals].

PMID- 9173601
TI  - [Euthanasia or therapy?].

PMID- 9173602
TI  - [Chemotherapeutics].

PMID- 9173603
TI  - [Concern for swine health].

PMID- 9173604
TI  - Suicidology: a look backward and ahead.
AB  - Using the metaphor of "a long run" to describe our progress in suicidology, the
      author looks back to discuss important concepts that have become well
      established, such as clues to suicide, ambivalence, crisis services, suicide
      consultations, and psychological autopsies. An example is the psychological
      autopsy of Marilyn Monroe. Follow-up studies of crisis center clients have
      indicated that chronically suicidal clients are at the greatest risk of suicide.
      Recommendations for the long-term treatment of such patients are provided.
      Research on youth suicide is reported. Finally, the author looks ahead toward new
      developments in training and treatment.

PMID- 9173605
TI  - Empirically based criteria for rational suicide: a survey of psychotherapists.

PMID- 9173606
TI  - Disentangling the interrelations between hopelessness, loneliness, and suicidal
      ideation.
AB  - We attempted to disentangle the interrelations between hopelessness, loneliness,
      and suicidal ideation, by comparing two conceptually driven models of their
      relationships, prospectively among 234 undergraduates, using a series of multiple
      regression/correlation equations. Model 1 framed loneliness as a risk factor for
      future suicidality that operates via its influence on hopelessness (the
      mediational view). Model 2 viewed hopelessness as a source variable that is
      predictive of both loneliness and suicidality, and postulated no relation between
      loneliness and suicidality beyond hopelessness. Model 2 received support, whereas
      Model 1 did not. We discuss the implications of our findings for the nomological
      status of hopelessness and loneliness as correlates of suicidality, and for
      exploration of the structural interrelations of suicide-related variables in
      general.

PMID- 9173607
TI  - The rate and characteristics of suicide attempters in the native Hawaiian
      adolescent population.
AB  - Native Hawaiian high school students, N = 1779, were surveyed for symptoms of
      psychopathology and suicide attempts in the previous 6 months. Seventy-seven
      (4.3%) of the students reported making a suicide attempt. There were no
      significant differences in prevalence rates for males and females. Depression,
      anxiety, aggression, substance abuse symptoms, and low family support, but not
      peer support, were significantly correlated with suicide attempts. On logistic
      regression, depression, substance abuse, and family support independently
      predicted attempts. The lack of gender difference may indicate a cultural
      characteristic of the Hawaiian population that differentiates it from mainstream
      American populations but likens it to the Native American population.

PMID- 9173608
TI  - Characteristics of suicidality among adolescents.
AB  - The identification of high-risk adolescent suicide attempters in a population of
      depressed and suicidal adolescents is of crucial importance. This retrospective
      study examined characteristics of suicidality (recent and lifetime, active and
      passive) and psychopathology (depression, aggression, impulsivity, stressful life
      events, SCL-90 dimensions) among four groups of depressed adolescent outpatients:
      (1) suicide attempters who required medical treatment (n = 84), (2) suicide
      attempters who did not require medical treatment (n = 57), (3) suicidal ideators
      who had never made a suicide attempt (n = 40), and (4) nonsuicidal patients (n =
      44). Results indicate that the nonsuicidal group could be differentiated from the
      three suicidal groups on the basis of suicidality and psychopathology, and that
      the three suicidal groups could be differentiated from one another on the basis
      of suicidality but not psychopathology. These findings are discussed in terms of
      the usefulness of certain self-report measures of suicidality for identifying
      suicidal adolescents and for differentiating among them. Furthermore, the
      findings suggest that psychopathological factors do not determine which suicidal
      adolescents make a medically dangerous suicide attempt and which do not.

PMID- 9173609
TI  - Classification of attempted suicide: a review of empirical studies, 1963-1993.
AB  - A review was carried out on empirical studies on the classification of attempted
      suicide over the period 1963-1993. Our aim was to investigate whether there is
      research evidence for a valid classification of homogeneous subgroups of suicide
      attempters. After assessment of the research quality, 32 studies were selected
      for comparison. Although there is lack of consistency among the studies,
      indications were found for two clearly distinguished subgroups characterized by
      mild and severe suicide attempts, which constitute the opposite poles of a one
      dimensional concept of severity.

PMID- 9173610
TI  - Music preference, depression, suicidal preoccupation, and personality: comment on
      Stack and Gundlach's papers.
AB  - In a sample of students, preference for country and western music was not
      associated with depression or suicidal preoccupation as has been suggested by
      Stack and Gundlach. However, preference for heavy metal music was associated with
      prior suicidal ideation. Stronger associations were found between music
      preferences and measures of psychoticism and extraversion.

PMID- 9173611
TI  - The growing use of firearms by suicidal older women, 1979-1992: a research note.
AB  - Suicide among older women (65+) has received very little attention despite
      increasing numbers of suicides in this population. An examination of national
      mortality data from the National Center for Health Statistics for the years 1979
      through 1992 shows an increasing trend in rates of suicide among older women and
      a declining trend among women under 65. Over the 14-year period, firearms
      replaced poisoning as the most prevalent method of suicide by women 65 and over.
      The results seem consistent with the assertion that the availability,
      familiarity, and cultural acceptability of firearms may play a role in the choice
      of suicide method among older women. Although violent death and the use of
      firearms are generally associated with males in our society, the trends reported
      here indicate that greater attention to firearm suicides among older women is
      warranted.

PMID- 9173612
TI  - A comparative evaluation of police suicide rate validity.
AB  - The authors assessed sensitivity, specificity, and predictive value of official
      police suicide rates and compared them to municipal workers. Deaths officially
      classified as suicide, accidental, and undetermined were submitted to a panel of
      medical examiners for validation. Six cases originally in the accident and
      undetermined rubric were reclassified as suicide. Official police suicide rates
      had less sensitivity (83.3% compared to 92.3%) of actual suicides than municipal
      worker rates. Police suicide rates also showed a lower negative proportion than
      municipal worker rates (86.2% compared to 98.7%). A generalizable sensitivity
      proportion equation for assessing suicide rates in other police groups is
      presented.

PMID- 9173613
TI  - Adolescent attitudes about death in relation to suicidality.
AB  - This study examined psychiatrically disturbed adolescents' history of exposure to
      suicide attempts, completions, and other deaths in relation to attitudes about
      life and death. A primary goal of the study was to study the mediating processes
      involved in the impact of loss on suicidality. Adolescents who experienced the
      suicide of a friend or immediate family member reported a weaker attraction to
      life and stronger attraction to death than adolescents lacking this experience.
      Exposure to attempted suicide resulted in attitudes indicating a stronger
      attraction to death and repulsion by life. We conclude that a comprehensive
      history of loss and assessment of current attitudes toward death are important
      aspects of evaluation and subsequent treatment of at-risk adolescents.

PMID- 9173614
TI  - Case consultation. The case of Ellen West revisited: a permitted suicide.

PMID- 9173615
TI  - [Odor perception in relation to age, general health, nutritional status, and
      dental status].
AB  - Many studies have shown that odour perception declines with age. Considering the
      possible role of age-related phenomena such as general health, dental health and
      nutrition in such a decline, their joint effect on variability in odour
      perception was evaluated in the present study. 73 apparently healthy adults aged
      from 53 to 86 years (median age = 66), living in the community, took part in this
      study. The SENIEUR protocol was used to assess the general health status and
      anthropometric measures were obtained to assess the nutritional status. The
      sensory detection threshold for isoamylacetate (banana odour) was determined as
      the lowest detectable odour concentration. Dental status was assessed by a
      questionnaire on the presence of natural teeth and wearing of dentures. Those in
      poor general health had significantly higher mean odour thresholds (2.35, SD =
      1.34), where threshold concentration was expressed as -log(mol/l), than those in
      good (3.47, SD = 1.46) or reasonably general health (3.75, SD = 1.02). Partial
      denture wearers had significantly higher odour thresholds (2.99, SD = 1.12) than
      those having only natural teeth (4.24, SD = 1.43). Significant correlations
      between age and anthropometrical values were found, indicating that with age,
      muscle mass particularly in women decreases (r = -0.50). Odour perception of
      women correlated significantly inversely with triceps skinfold thickness (r = 
      0.42), indicating that poor sense of small is associated with high body content
      of fat. Our results indicate that general health and dental state are important
      age-associated factors in odour perception. Since age does not show a significant
      independent effect, neither in an analysis of variance, nor in a multiple
      regression analysis, such factors tend to become more important than
      chronological age per se.

PMID- 9173616
TI  - [Friendship as a key to wellbeing: a course for women over 55 years old].
AB  - Friendship serves several important functions which contribute to well being in
      later life. The companionate function of friendship contributes to positive well
      being under normal circumstances. Friendship also provides social support during
      stressful events, such as loss of the partner, thus reducing negative well being.
      In addition to supporting socialization in new situations, friends serve a
      sustaining function; that is, they help sustain continuity of meaning of self and
      life experiences from the communal perspective of values and norms developed over
      the years. Various studies show that friendship is more important for older women
      than older men; women are more likely to maintain friendships until late in life
      and benefit from their friendships in adaptation to loss of the partner. A course
      was developed to assist older women in improving the quality or quantity of their
      friendships, to help them improve their well being. The course is based on a self
      help method and the principles of feminist therapy. A model describing four
      phases in which relational competence is important in friendship also forms the
      basis for the course. Disorders in friendship can be understood and influenced in
      terms of a cognitive perspective, aimed at customary thoughts on self, others and
      relationships. An evaluation study of the eleven participants in the first course
      demonstrates a significant decline in loneliness a year after the course as
      finished, as well as relevant improvements in the quality or quantity of
      friendships among several participants. The changes appear to be independent of
      the women's adult attachments styles, which influence their orientation in
      friendship. The conclusion is that the friendship course supports socially active
      lonely women, whose loneliness is not too extreme.

PMID- 9173617
TI  - [Aids in general daily activities can hardly replace professional home care.
      Results of a study among single 75-year-olds or older].
AB  - In this study we have examined for which ADL and mobility activities simple
      technical aids, including housing adaptations, can replace formal home care. A
      representative group of 498 single, independently living elderly persons, aged 75
      years or older, were interviewed orally. Many elderly interviewees (81.5%) had
      difficulties performing instrumental activities of daily living. Approximately
      one third of them received professional home care. We did not include technical
      aids for household activities in our study, since the distinction between
      technical aids and consumer products is unclear, and it was impossible to include
      all consumer products in our study. About 20% of the 120 elderly persons who had
      difficulties with personal care, received home care, especially in dressing and
      bathing. Only 5% of the elderly people with mobility problems (N = 208) got home
      care for mobility activities; most of them used technical aids or informal
      helpers. This means that stimulation of more mobility aids will not decrease the
      need for home care. Technical aids are very important for elderly people, but
      there are hardly any possibilities for replacing home care by the implementation
      of more technical aids.

PMID- 9173618
TI  - [Past cure and care: The "geriatric's" of nursing home medicine].

PMID- 9173619
TI  - [Priorities in prevention].

PMID- 9173620
TI  - [Direct antibiotic sensitivity testing in the treatment of urinary tract
      infections in a nursing home].
AB  - Urinary tract infections occur frequently in nursing homes. Treatment is usually
      empiric without microbiological investigation. Because there is widespread
      resistance to the most frequently used antibiotics, we tested a relatively simple
      method (direct sensitivity testing for 7 antibiotics) to get information about
      the antibiotic resistance. The results, with 49 urine samples in the evaluation,
      showed a concordance of our direct sensitivity test with conventional culture
      (the golden standard) of 89.8% (35/342 evaluations were not in concordance). The
      concordance for the result 'sensitive' was 98.8% (3/240 results showed 'false
      sensitive'), and the the result 'resistant' 68.6% (32/342 results showed 'false
      resistant'). Urinary tract infections in the nursing home can be treated more
      quickly and more adequately with antibiotics with the information obtained by
      direct sensitivity testing. This method can be recommended as an alternative to
      empiric treatment.

PMID- 9173621
TI  - [The coiled bodies and satellite microbodies of the oocyte nuclei in hibernating
      Rana temporaria frogs contain actin].
AB  - Immunocytochemical analysis of preparation of dispersed nuclei content in oocytes
      of III-IV stages of oogenesis, in terms of Dumont (1972), from hibernating grass
      frogs using monoclonal antibodies against actin, revealed two types of
      intranuclear structures containing this protein: coiled bodies (CB) and satellite
      microbodies (SM). Staining of these preparations with Rhodamin-phalloidin, known
      specifically to interact with fibrillar actin, did not reveal it in these
      structures. Results of our biochemical studies, using protease ESP32 specifically
      cutting only globular actin, are suggesting that both CB and SM contain globular
      actin. Gall et al. (1975) proposed that CB may be involved in assembling and
      sorting of small nuclear RNA for the three main RNA processing pathways: pre-mRNA
      splicing, pre-rRNA processing, and histone pre-mRNA 3'-end formation. Our finding
      of actin in CB allows a suggestion on actin involvement in the transport of RNA
      processing complexes from CB to some actual places where processing of RNA takes
      place. According to our previous data (Tsvetkov, Parfenov., 1994), SM participate
      in the karyosphere capsule formation. This process is preceded by SM fusion
      triggered presumably by actin.

PMID- 9173622
TI  - [The collagen-binding membrane proteins of connective-tissue cells].
AB  - The pattern of cell membrane collagen-binding proteins was analysed by affinity
      chromatography with collagen types I, III and IV columns. We have found that
      connective tissue cells have three polypeptides which are able to recognize the
      types of collagen. These proteins have molecular weights 130, 190, and 250 kDa
      (reduced) according to SDS-PAGE. Proteins with M. W. 130 and 250 kDa show high
      affinity to collagen type III and IV, but not to collagen type I. Protein with M.
      W. 190 kDa binds collagen type I only. The distribution of these proteins between
      cells from various tissues strongly correlates with the set of collagen types
      interacting with cells in the intact tissue.

PMID- 9173624
TI  - [XIIth All-Russian symposium on structure and functions of cell nucleus. St.
      Petersburg, October 22-24, 1996. Abstracts].

PMID- 9173623
TI  - [The mechanism of radioresistant DNA synthesis in ataxia telangiectasia].
AB  - Using DNA fiber autoradiography, DNA replication in cells of healthy donors and
      in those of patients with ataxia telangiectasia (AT) was estimated. A new fact
      has been demonstrated showing a decreased number of simultaneously operating in
      tandem groups of replicon clusters in AT cells compared to that in normal cells.
      The data obtained suggest a reduced frequency of activation in the adjacent
      replicon clusters in AT cells. It should be noted that the rate of fork movement
      remained unchanged in AT cells. Besides, the frequency of replication in adjacent
      replicon clusters remained unaltered after 5 Gy irradiation in AT cells, while
      the normal cells were radiosensitive to reduction in this replication parameter
      to the low level seen in both non-irradiated and 5 Gy irradiated AT cells. The
      relation of the above data to radioresistant DNA synthesis is discussed.

PMID- 9173626
TI  - II AIOM National Conference on Colorectal Cancer. Milan, Italy, 10-11 March 1997.

PMID- 9173625
TI  - [A comparative study of the morphofunctional changes in the thyroid of carp and
      rats as a result of being in an environment with an elevated lead level].
AB  - It has been noticed that the morphofunctional organization of the thyroid gland
      is similar in representatives of two different classes of vertebrates: in fishes
      and in rats. Exposure of experimental animals to ecological factors with
      increased lead levels was followed by a phase response (activation, depression)
      of various structural elements of the thyroid gland. Obvious differences in
      morphofunctional mechanisms of adaptation to chemical stress factors in fishes
      and rats were found. A possible relationship is discussed between the
      environmental pollution with heavy metals and the increased incidence of thyroid
      gland disease in human population.

PMID- 9173627
TI  - [Systemic sclerosis and environmental factors].

PMID- 9173628
TI  - [Children and environment].

PMID- 9173629
TI  - [From acute to chronic pain. Neurobiological aspects].

PMID- 9173630
TI  - [Headache in children].
AB  - In this article the last 30 years of research concerning headaches in children,
      especially migraine headaches, is reviewed. The article is directed towards
      epidemiology, identification, classification, pathophysiology and management.
      Headache is a common medical complaint in children and adolescents, but diagnosis
      can be difficult, particularly in the very young. Many know far too little about
      how to recognise a child with headache and how to deal with it.

PMID- 9173631
TI  - [Occupational systemic sclerosis in men].
AB  - An analysis of the history of 28 men suffering from systemic sclerosis, diagnosed
      at our department during the last 25 years, showed that 21 (75%) had been subject
      to exposures previously suggested to be of importance in occupational
      scleroderma. The exposures were revealed by patient files, reports to health
      authorities, interviews and/or answers to questionnaires. Organic solvents being
      the most frequent exposure. This was found in thirteen of the patients (46%). A
      significant difference was found between scleroderma patients and control
      patients not suffering from connective tissue diseases in relation to total
      number of subjects exposed to one or several of the agents in question.

PMID- 9173632
TI  - [Risk factors for suicide in patients with disseminated sclerosis].
AB  - The purpose of the present study was to describe risk factors for suicide in
      patients with multiple sclerosis (MS). The study is based on available
      information about MS-patients identified in the Danish MS Registry with onset of
      disease in the period 1950-1985. In order to characterize MS suicides with
      respect to risk factors comparisons were made for male and female suicides, and
      for various groups of MS suicides according to disability status. The male
      suicides were characterized by a tendency to commit suicide in the age interval
      40-49 years, the use of a violent method, previous suicidal behaviour, previous
      mental disorder, recent deterioration of MS, and moderate disability. For women
      the characteristics were less distinct. Patients with a severe course of MS had
      been subjected to more risk factors before the suicide. Careful counselling and
      good information to MS-patients are advocated.

PMID- 9173633
TI  - [Sexual function in patients with disseminated sclerosis. A 5-year follow-up
      study].
AB  - Sexual dysfunction is known to occur in multiple sclerosis (MS). The purpose of
      the study is to describe the change in sexual function and symptoms in a five
      year follow-up study. Forty-nine patients (27 females, 22 males) with definite MS
      were interviewed and examined. The number of patients with sexual dysfunction
      increased significantly (p = 0.004) and involved females and males equally. Males
      usually had one or two symptoms, while females frequently had two or more
      symptoms. It is concluded that the risk of sexual dysfunction increases over
      time. Further studies concerning treatment possibilities are needed.

PMID- 9173634
TI  - [Breech delivery. Selection by X-ray pelvimetry].
AB  - An attempt was made to evaluate the possible benefit of selecting women for
      vaginal breech delivery at term by radiological pelvimetry. Information from
      medical records on 276 singleton breech deliveries were analysed. A total of 188
      breech presentations were diagnosed before the onset of labour, pelvimetry was
      performed in 74 women, where pelvic dimensions too small for recommendation of
      vaginal breech delivery were found in 30 cases. The overall rate of caesarean
      section was 78%, among diagnosed patients it was 84% and 64% among undiagnosed
      breech presentations. Rates of morbidity (low Apgar score and admission to the
      neonatal care unit) did not differ significantly between infants delivered
      vaginally or by elective caesarean section. The material, however, is too small
      for valid conclusions regarding safety of vaginal delivery of term breech in
      women selected by criteria including estimate of pelvic size.

PMID- 9173636
TI  - [Forensic autopsies performed because of suspected occupational disease during
      the period 1987-1991--counties of Funen and Southern Jutland. Guidelines for
      physicians' notifications and a review of autopsy practice during 5 years].
AB  - One hundred and thirty-six forensic autopsies were conducted at the Institute of
      Forensic Medicine, University of Odense, Denmark (covering the counties of Funen
      and Southern Jutland) between 1987 and 1991 suspecting occupational disease as
      the cause of death. The autopsy were requested by the National Board of
      Industrial Injuries (NBII). The most frequent exposures were asbestos, solvents,
      sand, dust and welding fumes. Death was caused by lung disease in 92/136 of the
      cases, of which 48 were lung cancers and ten mesotheliomas. Totally, cancer
      diseases were found to be the cause of death in 70/136. Comparing data from the
      official death register and from NBII on mesothelioma it is concluded that only a
      minor part of the deaths caused by occupational disease are reported. Only a
      fraction of the diseases listed in the official Danish inventory for occupational
      diseases were represented among these deaths. To ensure the relatives their
      rightful compensation and improve the statistical data used for prevention, it is
      important that doctors report all deaths which may have been caused by
      occupational diseases.

PMID- 9173637
TI  - [Listeriosis in the third trimester of pregnancy].
AB  - A case of fatal intrauterine listeriosis in the third trimester of pregnancy is
      described. The patient presented with preterm labour and was delivered by
      emergency caesarean section on suspicion of foetal distress. The child was
      stillborn. The diagnosis was based on specific histopathological findings in the
      foetus and the placenta.

PMID- 9173635
TI  - [Community psychiatric treatment and needs of admission of psychiatric patients.
      A controlled study 5 years after introduction of a community psychiatric center].
AB  - The utilization of the psychiatric in-patient services was evaluated in the
      intervention district and compared with a selected control district. The number
      of admissions and in-patient days were similar before admission to the community
      psychiatric service. As a result of the intervention the number of admissions to
      hospital and the length of in-patient hospital stay decreased significantly,
      resulting in a reduction of total number of in-patient days by 47%. The findings
      of other recent studies follow the same pattern. The reduction in in-patient days
      was significant in the group of schizophrenic patients.

PMID- 9173638
TI  - [Gastroesophageal reflux and "near miss" sudden infant death syndrome].
AB  - A case of an infant with gastro-oesophageal reflux is presented. Her symptoms,
      which were very similar to those of "near miss" sudden infant death syndrome
      (SIDS), were resolved by antireflux surgery. Two of her brothers died with the
      diagnosis SIDS.

PMID- 9173639
TI  - [How blind can one be?].

PMID- 9173640
TI  - [Gene therapy of malignant brain tumors?].

PMID- 9173641
TI  - [Treatment of apoplexy].

PMID- 9173642
TI  - [Malaria prophylaxis. Effects and side-effects of drugs used for prevention of
      malaria].

PMID- 9173643
TI  - [Insertion of autografts after acute damage of the common carotid artery.
      Experimental microvascular anastomoses after balloon dilatation].
AB  - The objective of our investigation was to study the patency rates of anastomoses
      in arteries, damaged by a balloon dilatation, in a training model of
      microvascular surgery. In general anaesthesia, a balloon dilatation was repeated
      5 times in 31 left common carotid arteries of female Wistar rats (body weight:
      250 to 350 g). A common carotid artery autograft of 4 mm was harvested 1 minute
      after reflow, turned 180 degrees, and reinserted into the artery. The reflow of
      the vessels was investigated by micro-Doppler ultrasound equipment. Autografts
      without balloon dilatation or any other intended damage were performed in further
      26 common carotid arteries. In addition, in further 14 common carotid arteries
      the balloon dilatation was the sole damage. The vessels were harvested and
      investigated postoperatively after perfusion with 3% glutaraldehyde at 1 day, 7
      days, and 1 month. The balloon dilatation in no instance caused an occlusion of
      the vessel as judged by the micro-Doppler ultrasound. One vessel was found to be
      occluded after reflow was allowed following insertion of the autograft in the
      group without balloon dilatation. However, this vessel proved to be patent after
      explantation (patency rate: 100%). In the group with balloon dilatation preceding
      the autograft insertion, by micro-Doppler ultrasound, 16 vessels were occluded
      and 14 were patent. At different times of follow-up, in this group the summarized
      patency rates were 50%. The patency differences in both groups with autografts
      proved to be significant, both after micro-Doppler imaging and by histological
      evaluation (p < 0.001). For clinical use the balloon dilatation is recommended to
      remove a thrombus or to dilate a spastic vessel segment in anastomized vessels
      threatening the success of microvascular flaps. In this training model of
      microvascular surgery we demonstrated the thrombogenic effect of balloon
      dilatation.

PMID- 9173644
TI  - [Knee joint arthrosis of the miner--an occupational disease. On the double
      etiology of gonarthrosis of the miner].
AB  - The etiology of the osteoarthrosis is a multifactorial causality. Some factors,
      the preosteoarthrotic deformities, which concur with the recovery, are well
      known. The factors of the primary osteoarthrosis are still in the dark and
      require research. It is presented, that by the miner, the co-operation of several
      preosteoarthrotic deformities, especially the preosteoarthrotic deformity
      "repeated knee microtrauma" with unknown factors, leads to the high rate of knee
      wear and tear which makes the osteoarthrosis after occupational knee strain by
      mineworkers into an occupational disease.

PMID- 9173645
TI  - [Pathologic humeral fracture in secondary osteosarcoma of the humerus: a rare
      complication of osteodystrophia deformans Paget].
AB  - Pathological fracture in histologically proven post-Paget osteosarcoma of the
      humerus is a rare complication. Due to individual requests as well as age and
      comorbidity, a course of primary palliative treatment was chosen in the present
      case. Survival time after diagnosis was 9 months and the patient died of a tumor
      independent disease. Even in combined treatment, consisting of surgery and (neo
      )adjuvant radio-/chemotherapy, prognosis of osteosarcomas secondary to Paget's
      disease remains very disappointing. Therefore, in treatment of this highly lethal
      tumor the patient's individual requests and personal situation often require more
      consideration than in many other malignancies.

PMID- 9173646
TI  - [Case report of primary chronic osteomyelitis].
AB  - We report 3 individually different cases of primary chronic osteomyelitis.
      Neither the plasmacellular nor the sclerosing forms caused diagnostic or
      therapeutic difficulties whereas the case of a 40-year old male patient with a
      Brodie abscess in the tibial head could not be diagnosed unless the untreated
      abscess had perforated into the knee itself and empyema of the knee leaded to
      operative treatment and finally diagnosis of the Brodie abscess. Follow-up X-rays
      in weekly periods or MRT could have been helpful to avoid delayed diagnosis.

PMID- 9173647
TI  - [Continuing education: current status].

PMID- 9173648
TI  - Clinical pathology data.

PMID- 9173649
TI  - [Selected immunologic markers for evaluation of peripheral blood in patients with
      internal endometriosis].
AB  - In group of 16 patients with internal endometriosis verified by histopathological
      investigations following immunological indices in peripheral blood were
      estimated: 1) number of leucocytes and neutrophils, 2) neutrophil adherence to
      fibres, 3) phagocytic activity of neutrophil using the latex granules, 4)
      concentration of immunological complexes in serum. The results were compared with
      those in control group (20 healthy women). In patients with internal
      endometriosis compared to control group the increase of the number of leucocytes
      and neutrophils and decrease of phagocytic activity of neutrophils were observed.

PMID- 9173650
TI  - [An approach concentrated on the individual--possibilities of use in general
      medical practice].
AB  - On the clinical image of disease does not only consist of the typical symptoms of
      illness, but also depends upon the patients emotional experience which can modify
      the course of disease and therapy. It needs to form the therapeutical relations
      patient-physician, which will be able to take influence upon the emotional state
      of patient. C. Rogers's "Person-centered approach" create such possibility. It
      has application in the clinical practice in psychiatry and psychology but it
      seems that in can be useful in the general medical practice. The attitude of the
      therapeutist in relationship with patients has to express with congruence,
      unconditional positive regard and empathic understanding. The ability of
      empathical perception of patient's emotional state is one of very important
      physician's skills and influences on the patient's level of satisfaction with
      medical care. The "Person-centered approach" utilizes the inherent tendency of
      the patient to develop all his capacities of personality in the therapeutical
      process.

PMID- 9173651
TI  - [The basic algorithm for treatment of primary hypertension].

PMID- 9173652
TI  - [Preoperative autotransfusion and hemodilution and its value in reconstructive
      vascular surgery].
AB  - Autotransfusion and haemodilution are the most safe and well known methods of
      blood protection in patients planned for vascular operations. During
      reconstructive vascular surgery autotransfusion with hypovolemic or normovolemic
      haemodilution were used. In the I group of patients hypovolemic haemodilution was
      done. In the II group of patients vascular bed was filed up with Ringer solution
      or with 6% solution of hydroxyethyl starch. The type of haemodilution and its
      influence on haemodynamics were estimated. Investigations were done by
      echocardiograph: ATL ULTRAMARK 8. It was concluded that the most effective are
      autotransfusion and normovolemic haemodilution with filing up vascular bed with
      Ringer solution.

PMID- 9173653
TI  - [Evaluation of the accuracy of arterial pressure measurements with different
      types of devices used for self-monitoring].
AB  - The self-control is the important item in hypertension treatment. The results of
      blood pressure measurements were received by using various types using different
      of oscillometric equipment (thumb, wrist and arm manket) and compared with the
      outcomes of mercury sphygmomanometer which was used in the same trial. The
      satisfactory correlation of results from different types of equipment was
      confirmed with the exception of the thumb oscillometric apparatus results.

PMID- 9173654
TI  - [Dermoid cysts of the oral cavity].
AB  - The authors describe ethiology, clinical picture, diagnosis and treatment of the
      dermoid cyst of oral cavity floor. They show the advantages after using
      ultrasonography and computer tomography in treatment of these cysts.

PMID- 9173655
TI  - [Noninvasive transcutaneous cardiac pacing].
AB  - The method of Noninvasive Transcutaneous Cardiac Pacing (NTCP) is presented in
      this paper. The authors describe the history of this stimulation type and
      difficulties during the first clinical attempts at pacing. Then they focus on
      cardiac activation by noninvasive cardiac pacing. Subsequently they analyse the
      effect of electric field on the myocardium and skeletal muscles. The hemodynamic
      aspects of NTCP take an important place. A the end the authors review the
      clinical application of NTCP.

PMID- 9173656
TI  - [Pseudoaneurysm of the pancreas].
AB  - A case pancreas pseudoaneurysm in chronic pancreatitis in 41-years old man is
      described. A big (12 cm) cyst with rotating fluid inside has been determined in
      USG examination. The patient has been operated on. The injury of the hepatic
      communis artery was the source of bleeding into the cyst. The artery has been
      ligated and the Jurasz operation has been performed. Post-operative course
      uncomplicated.

PMID- 9173657
TI  - [A case of toxic epidermal necrolysis with a low level of IgA in serum].
AB  - A case of the toxic epidermal necrolysis in a 52-year-old woman treated for
      hypoxia of cerebral trunk during the severe attack of bronchial asthma and the
      bacterial infection of respiratory system was described. The pause of toxic
      epidermal necrolysis was treated with ceftriaxone and cefuroxime. The woman died
      on the 20th day of disease.

PMID- 9173658
TI  - [Use of computerized tomography for localization of a foreign body impacted into
      the cranium].
AB  - A case is presented of impaction of a metal bar into the cranium i an 8-year-old
      child. The significant importance for the therapeutic management was radiological
      examination, especially CT of the head. It made easier the determination of the
      foreign body locality in relation to the anterior cranial fossa and could allow
      to do the assessment of the resolution of air accumulation in the frontal lobe.

PMID- 9173659
TI  - [Poisoning with spotted and red mushrooms--pathogenesis, symptoms, treatment].
AB  - Amanita pantherina and Amanita muscaria are commonly occurring mushrooms in
      Polish forests. They contain ibotenic acid and muscimol: the substances reacting
      with neurotransmitter receptors in central nervous system. The ingestion of these
      mushrooms produces a distinctive syndrome consisting of alternating phases of
      drowsiness and agitation with hallucinations, and sometimes with convulsions. The
      diagnosis of Amanita pantherina or Amanita muscaria poisoning is established by
      means of mycologic investigation of gastric lavage. The treatment is only
      symptomatic, and the prognosis is usually good.

PMID- 9173660
TI  - [Vomiting as a symptom of a developing psychological eating disorder in a 15-year
      old girl].
AB  - A case of difficulties in diagnosis of anorexia nervosa in a 15-year-old girl is
      reported. Before 1960, anorexia nervosa was rarely recognized, and bulimia was
      not known, as a nosological entity. Over the last two decades the occurrence of
      anorexia nervosa and bulimia has been on the rise. The disorders of ingestion
      usually begin as merely dietetic habits. However, they may, lead to heavy losing
      of weight accompanied by emaciation. Successful treatment depends on appropriate
      therapy managed by a psychologist, psychiatrist and endocrinologist.

PMID- 9173661
TI  - [Routine health screening, yes or no? It depends].

PMID- 9173662
TI  - [Avalanche emergency. New aspects of the pathophysiology and therapy of buried
      avalanche victims].
AB  - A series of investigations on the pathophysiology and management of persons
      buried in an avalanche has been undertaken over the past few years in response to
      increased awareness of the importance of emergency medical treatment of avalanche
      victims and the fact that the high mortality rate has not decreased in spite of
      the improvement in rescue techniques. This paper is the very first review of the
      problems encountered in avalanche disasters. The developments over the past 20
      years, in particular, are summarized and discussed. Furthermore, current opinions
      and recommendations on optimal rescue procedure, as well as the prevention of
      such emergencies are presented. Precise assessment of the survival probability
      after burial under an avalanche and recognition of the prognostic importance of
      an air pocket, but only limited role of hypothermia, provide the basis for new
      concepts governing therapy and triage by the emergency doctor. Resulting
      guidelines have been endorsed by the Emergency Medicine Subdivision of the
      International Commission of the Alpine Rescue Services (ICAR) and these
      recommendations are intended for implementation by organised rescue teams in
      order to reduce secondary deaths following successful extrication of victims from
      the avalanche masses. However, the chance of being rescued alive depends
      primarily on the rapidity of extrication, i.e. how quickly the rescue teams are
      alerted and transported to the disaster area in the first instance, then how
      quickly the victims are located and extricated. In order to reduce the mortality
      additional preventive measures must be introduced to avoid complete burial if
      possible, or appreciably hasten the rescue procedure. The very steep drop ("fatal
      kink") in survival probability as from 15 minutes after burial underlines the
      absolute necessity of the mastery of efficient rescue procedure by uninjured
      companions. Improvement of the technical developments for the avoidance of total
      burial (avalanche air bag) and optimization of the electronic location
      (transceiver) of buried skiers by uninjured companions are essential future
      requirements. Nonetheless, primary prevention remains of paramount importance in
      governing decision making by offpiste skiers. Correct assessment of the inherent
      risks according to the prevailing circumstances and strict adherence to safety
      rules take precedence over all other considerations.

PMID- 9173663
TI  - [Follow-up studies of routine health screening in Vorarlberg 1986-1994].
AB  - In this longitudinal study we observed a sample of people who participated in the
      general health screening program in Vorarlberg between 1986 and 1994. The aim was
      to analyse the changes in the parameters, body-mass index, diastolic and systolic
      blood pressure, blood glucose, cholesterol, gamma-GT and triglycerides of 1205
      women and 718 men over this period. Using the baseline values recorded in 1986 as
      reference the sample was divided into groups with normal, slightly increased and
      highly increased values for the parameters. On average, the risk factors of
      people with highly increased baseline values decreased on both a short-term (1986
      1988), and a long-term basis (1986-1994). The only exception was the body-mass
      index, which showed a slight reduction in the first two years and a slight
      increase in the long run. The normal baseline values rose in all the variables
      within the period of observation. Sex differences must be considered with regard
      to body-mass index, cholesterol and triglycerides, age differences are
      significant with regard to body-mass index, systolic blood pressure and
      cholesterol. The results of the study point to the usefulness of regular
      participation in general health screening programs. They show, in particular,
      that the risk factors for civilization-induced diseases diminish visibly in the
      group of highly endangered people.

PMID- 9173664
TI  - [Intestinal lavage solution for orthograde intestinal irrigation].
AB  - Gut lavage by ingestion of large volumes of electrolyte solutions has been shown
      to be an effective method of cleansing the colon before colonoscopy, barium enema
      or surgery. Absorption of water and electrolytes, which might be hazardous to
      patients who are unable to readily excrete an additional sodium and/or water
      load, is prevented by addition of non-absorbable substances to the solutions, but
      systematic studies are lacking. We have evaluated the influence of three
      solutions for gut lavage with different electrolyte composition (sodium
      concentration 67 mmol/l and 125 mmol/l) and addition of different non-absorbable
      substances (mannitol and polyethylene glycol [PEG]) on water and electrolyte
      homeostasis and subjective tolerance, both in healthy volunteers and in patients
      before endoscopy of the colon. In a randomized, blind study 6 liters of the three
      solutions were administered via a nasogastric tube to 6 healthy volunteers during
      4 hours (i.e. 1.5 l/h). Body weight, serum concentrations of sodium, potassium
      and of phosphate were measured before infusion of the solution and after the last
      rhythmic rectal effluent. No significant changes were observed in any of the
      studied parameters and the incidence of side effects (nausea, abdominal cramps)
      was comparable. In an additional clinical double blind study, 26 patients before
      diagnostic colonoscopy were asked to drink 4 liters of the gut lavage solutions
      as quickly as possible in order to clean out the colon. The time for drinking was
      significantly shorter in patients using the mannitol and low sodium solution (204
      +/- 70 minutes) than in patients drinking the solution with polyethylene glycol
      and a high sodium concentration (387 +/- 137 minutes). There was a tendency to a
      longer drinking period in patients ingesting the solution with polyethylene
      glycol and low sodium (306 +/- 106 minutes). Thus, the acceptance for solutions
      containing polyethylenglycol and high sodium concentration is reduced because of
      low palatibility. Again no influence on serum electrolyte concentrations or body
      weight could be observed in any patient, the spectrum of side effects was similar
      and the cleansing effect of all three solutions was adequate. In conclusion
      solutions for gut lavage containing a balanced electrolyte concentration and
      nonresorbable substances such as mannitol or polythylenglycol are equivalent.
      However, solutions containing mannitol and a low sodium concentration are better
      tolerated by the patients but the use of mannitol is limited because of the risk
      of releasing explosive gases during interventional endoscopy. To enhance the
      acceptance and palatibility of solutions for gut lavage containing
      polethylenglycol the addition of flavoured substances is recommended.

PMID- 9173666
TI  - [Does unemployment cause illness?].

PMID- 9173665
TI  - ["Coca-Koller" and hist friends. On the 140th birthday of the Vienna Jewish trio:
      Carl Koller (1857-1944), Sigmund Lustgarten (1857-1911) and Sigmund Freud (1856
      1939)].
AB  - The lives of Carl Koller (1857-1944), Sigmund Lustgarten (1857-1911) and Sigmund
      Freud (1856-1939) are characterized by several interesting similarities. In their
      early achievements in medical research they were pathfinders of the first
      successful local anesthetic: cocaine. All three became later victims of
      antisemitism. Attention is paid to their personal relationship during their time
      in Vienna, on occasion of the 140th anniversary of their birth.

PMID- 9173667
TI  - [Presurgical diagnosis of epilepsy and surgical epilepsy treatment].
AB  - 20% of patients with focal epilepsy suffer from medically refractory seizures.
      Many of these patients can be cured by a surgical intervention removing the brain
      area where the seizures are originating (epileptogenic zone). 6000 patients in
      Austria would benefit from epilepsy surgery with an additional 150-200 new
      patients appearing each year. Potential candidates have to undergo an extensive
      presurgical work-up. During the non-invasive Phase I each patient is evaluated
      with an intensive video-EEG monitoring with scalp-EEG, a high resolution MRI, a
      SPECT and/or PET, a neuropsychological evaluation and a Wada-test. If the
      epileptogenic zone cannot be localized adequately with these methods, invasive
      electrophysiological techniques (epidural Peg-electrodes, Foramen-ovale
      electrodes, depth electrodes, subdural strip and grid electrodes) have to be
      applied. Operative strategies for temporal lobe epilepsies include antero-mesial
      temporal lobe resections and selective amygdala-hippocampectomies. Extratemporal
      epilepsies are treated by cortical resections guided by structural and
      electrophysiological parameters. The new technique of multiple subpial
      transections facilitates treatment of seizures originating in essential brain
      regions. Catastrophic epilepsies of early childhood often are caused by extensive
      pathologies affecting one hemisphere and can be treated successfully by large
      multilobar resections or hemispherectomies. Epilepsy surgery renders 70-80% of
      patients seizure free and thus can be regarded as an effective and safe treatment
      option for patients with medically refractory focal epilepsies.

PMID- 9173668
TI  - [Maintenance therapy with 20 mg fluoxetine. Results of an administration study of
      1,737 depressed patients].
AB  - An application study was carried out in 1993/94 on the use of fluoxetine for the
      continuation therapy of depression. 1737 patients received fluoxetine at a dosage
      of 20 mg per day over a period of 6 months. Diagnosis was made by clinical
      evaluation of phenomenology and ICD-10 classification. Over the observation
      period physicians rated the course of illness according to severity of the
      depression, somatic complaints and therapeutic efficacy on a scale graded 1-4.
      Side effects and concomitant medication were also noted. Coincidentally, patients
      recorded subjective satisfaction with therapy, as well as side effects. In a
      subsample of 423 patients the physicians additionally used a modified version of
      the Hamilton Depression Rating Scale (HRDS) for behavioural ratings. Standard
      assessment was performed after the 2nd and 6th weeks of treatment and again after
      the 3rd and 6th months. The rating scale showed a decrease in depressive
      symptomatology and somatic complaints at the end of treatment in 53% and 44% of
      patients, respectively. Treatment efficacy was rated as excellent in 82% of
      cases, as evaluated by the physicians; patients were satisfied in 89% of cases.
      These results are strengthened by the reduction from 22.4 +/- 7.0 to 9.2 +/- 6.4
      in the subsample of 423 patients according to the HRDS, equivalent to a decrease
      in depression symptomatology of 59%. This study is the first open phase IV trial
      in Austria investigating continuation therapy with 20 mg fluoxetine per day and
      confirms results obtained in international multicentre placebo-controlled studies
      involving considerably smaller numbers of patients.

PMID- 9173669
TI  - [Cardiovascular diseases caused by unemployment? An analysis from the viewpoint
      of social medicine].
AB  - Unemployment has become a sociopolitical problem of great importance in the
      Western industrialised countries. Although negative effects on social life and
      psyche resulting from unemployment are regarded as scientifically accepted today,
      a possible causal relationship between job loss and somatic illnesses is still a
      matter of controversy. A possible target organ is the cardiovascular system. The
      aim of this study was, therefore, to check by means of extensive literature
      analysis to what extent unemployment can be seen to influence cardiovascular
      morbidity. Particular attention was paid to the method used and the clinical
      relevance of the results. Person-related epidemiological studies published since
      1980 which investigated changes in cardiovascular risk factors associated with
      unemployment or prevalence rates of manifest disease influenced by unemployment,
      were included in the final evaluation. In some cases statistically significant
      associations were found between unemployment and the increase in cholesterol
      levels or systolic/diastolic blood pressure, but the clinical relevance of such
      slight changes is questionable. To consider unemployment as an independent,
      social, cardiovascular risk factor is at present unwarranted. An increase in the
      prevalence rates of coronary heart disease or arterial hypertonia causally linked
      in some studies with unemployment is scientifically questionable due to severe
      methodological shortcomings. On the basis of the currently available
      methodologically acceptable studies, the question of a qualitative contribution
      of unemployment to cardiovascular disease cannot be answered conclusively.

PMID- 9173670
TI  - [WIT 97. The heart in the intensive care patient. Vienna, February 27-March 1,
      1997. Proceedings and abstract].

PMID- 9173671
TI  - [The heart and ischemia: stunned-hibernating myocardium].

PMID- 9173673
TI  - [Pulmonary artery hypertension].

PMID- 9173672
TI  - [The heart in infection and MODS (multiple organ dysfunction syndrome)].
AB  - Dysfunctioning of the heart forms part of the multiple organ dysfunction syndrome
      (MODS) in sepsis and SIRS. This acute septic cardiomyopathy is often
      underestimated in degree and relevance, although yet in fact 10% of all sepsis
      fatalities are due to intractable heart failure. This potentially reversible
      cardiomyopathy is characterized by a considerable pump failure, is not primarily
      ischemic, coronary blood flow being normal or even enhanced; left and right
      ventricle are enlarged as a consequence of an increased ventricular compliance.
      Damage of the heart can further be aggravated in case of an additional right
      ventricular impairment due to pulmonary hypertension in ARDS. SIRS-cardiomyopathy
      in non-infectious MODS has common traits with acute septic cardiomyopathy. The
      pathogenesis of heart disease in sepsis and SIRS is multifactorial, the
      endotoxin/TNF-alpha/NO/cGMP-cascade representing a main negative inotropic axis.
      Therapy of acute septic cardiomyopathy and SIRS-cardiomyopathy at present still
      is mainly symptomatic (volume substitution, inotropic/vasoactive agents), causal
      therapeutic principles are, however, put to test in the context of a
      comprehensive concept of causal sepsis treatment.

PMID- 9173674
TI  - [Treatment outcome in patients with chronic subdural hematoma with reference to
      age and concurrent internal diseases].
AB  - The chronic subdural hematoma (CSH) is a disease in elderly patients beyond the
      5th decade. Treatment of CSH is normally a burr hole trephination and subdural
      drainage. Although this technique is simple, lethality is reported to be up to
      20% in literature. The records of 314 patients with CSH were analyzed. Attention
      was focussed on complicating diseases and distribution of age. Patients were
      categorized neurologically before and after trephination using the Bender scale.
      The portion of patients suffering from cardiological diseases was 14.3%, 6.7%
      were treated by anticoagulants because of cardiac valve implant. Alcoholics were
      found in 15.9% of patients and hypertension in 12.8%. Complicating diseases were
      found in 51.3% of patients. Multiple internal diseases are likely to affect
      prognosis more than hematoma thickness. These patients also brought about a
      higher rate of infection (4.8%), secondary hemorrhages (2.5%), pneumonia (3%) and
      seizures (5%) after trephination. Lethality was highest in patients with diabetes
      mellitus, cardiogenic diseases and hypertension as well as in elderly patients.
      The latter have also a poor post-operative outcome: 22 patients died. In contrast
      to hematoma thickness and midline shift, which do not have any influence on
      outcome, prognosis is mainly determined by age, complicating diseases,
      hypertension and diabetes mellitus. The chronic subdural hematoma is often found
      in multi-morbid patients.

PMID- 9173675
TI  - [Cerebrolysin in treatment of painful diabetic neuropathy].
AB  - Cerebrolysin is a peptide solution with free amino acids and biologically active
      peptides showing neurotrophic efficiency. In a placebo-controlled longitudinal
      study we investigated the effect of that drug for treatment of painful diabetic
      neuropathy in 20 type-II diabetic patients (9 women, 11 men, mean age 63 +/- 9
      years, duration of diabetes 14 +/- 7 years). Patients received daily a
      cerebrolysin-infusion (20 ml in 500 ml Ringer) over a period of 10 days. In an
      age- and diabetes-duration matched placebo group of 10 type-II diabetic patients
      (7 women, 3 men, age 66 +/- 9 years, duration of diabetes 12 +/- 5 years) vitamin
      B infusion was administered (5 ml vitamin B complex in 500 ml Ringer) during 10
      days. We compared a five-item symptom score scale (FIS) for pain, dysesthesia,
      paresthesia, nightly exacerbation, and sleep disturbances (grade 0 to 3) and a
      graphic visual analogue rating scale (VAS) for recording the magnitude of the
      pains (scale 0 to 100 mm) at the beginning and the end of the infusion therapy as
      well as 6 weeks later. Cerebrolysin was associated with a significant decrease in
      total FIS score from 8.7 +/- 1.9 at the start of therapy to 5.1 +/- 2.2 after 6
      weeks (p < 0.001), and to a reduction of the VAS score from 4.2 +/- 0.8 to 2.8 +/
      0.9 (p < 0.001) during the same period of observation. In contrast in the
      placebo group the total FIS score decreased only from 7.9 +/- 1.2 at the
      beginning to 6.6 +/- 1.1 (p < 0.05) 6 weeks later and the VAS score from 4.5 +/-
      0.6 to 4.0 +/- 0.5 (NS). Thus cerebrolysin led to a significant subjective
      improvement of painful diabetic neuropathy in type-II diabetic patients at least
      for a period of 6 weeks.

PMID- 9173677
TI  - [Statistics--lying, but properly].

PMID- 9173676
TI  - [Pupillary diameter and pupillary reactions in heroin dependent patients and in
      patients participating in a methadone and morphine replacement program].
AB  - The computer-assisted static and dynamic light evoked pupillometry (TV
      pupillometer 1050, Whittaker Corp.) had been proved to be a sensitive procedure
      for assessment of the effect of psychoactive drugs. Therefore, this method was
      used in 26 heroin dependent patients (mean age 24.42 years), 20 methadone
      substituted patients (mean age 29.75), and 20 morphine-substituted patients (mean
      age 30.65 years) to answer the question whether there were no differences within
      the patient groups but significant differences between the patients and healthy
      normals. Indeed, pupillary diameter (vegetative activation) as well as relative
      change (pupillary reagibility) showed no significant differences between the
      heroin dependents, the methadone substitution group and the morphine substitution
      group. However concerning pupillary diameter and relative change the patient
      groups differed significantly from the healthy controls. Onset latency revealed
      no differences within the patient groups and between patient groups and healthy
      controls respectively. Thus the variable pupillary diameter and relative change
      could be used to assess the additional application of opiates in patients
      participating in a substitution program.

PMID- 9173678
TI  - In vitro metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide in
      the Fischer 344 rat and New Zealand white rabbit.
AB  - 1. The nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) underwent
      nonenzymatic hydrolysis to N-(3,5-dichlorophenyl)succinamic acid (NDPSA) in
      buffer, rat liver and kidney homogenates, and rabbit liver homogenates. 2. In the
      presence of NADPH, rat liver homogenates converted NDPS to NDPSA and N-(3,5
      dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA). 3. Using liver homogenates
      from the phenobarbital (PB)-pretreated rat, 2-NDHSA production was increased 5
      fold, and the metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and
      N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3NDHSA) were also detected.
      Formation of these latter metabolites was suppressed by CO or omission of NADPH.
      No hydroxylated metabolites were detected when NDPSA was incubated with PB
      induced rat liver homogenates. 4. Oxidative metabolites were not produced when
      NDPS was incubated with kidney homogenates from the control or PB-pretreated rat.
      5. NDHS underwent rapid hydrolysis in buffer to yield 2-NDHSA and 3-NDHSA. 6.
      Rabbit liver homogenates converted NDPS to NDPSA, 3,5-dichloroaniline (DCA), and
      succinic acid (SA). Production of DCA and SA was inhibited by the amidase
      inhibitor bis-p-nitrophenyl phosphate. Oxidative metabolism did not occur in
      rabbit tissue. 7. These experiments demonstrate that a PB-inducible form of rat
      liver P450 converts NDPS to NDHS, which then undergoes hydrolysis to 2-NDHSA and
      3-NDHSA. An alternative route of production for 2-NDHSA and 3-NDHSA, via
      hydroxylation of NDPSA, does not occur. In rabbit liver NDPS metabolism was
      primarily amidase-mediated.

PMID- 9173679
TI  - Suppression of intestinal and hepatic cytochrome P4503A in murine Toxoplasma
      infection. Effects of N-acetylcysteine and N(G)-monomethyl-L-arginine on the
      hepatic suppression.
AB  - 1. Cytochrome P4503A (CYP3A) expression was studied in a murine model of
      infection. Mice were infected with a cystogenic strain of Toxoplasma gondii and
      microsomes were prepared for liver homogenates and jejunum villus tip enterocytes
      on day 10 postinfection. Total cytochrome P450 (CYP) and CYP3A were quantitated,
      and CYP3A activity was determined. 2. In the infected mouse, total CYP and CYP3A
      contents fell in the liver (-39 and - 49% respectively) and intestine (-43 and -
      48 % respectively), as did the rate of metabolism of erythromycin (Ery) and
      cyclosporine A (CyA), two markers of CYP3A activity (-36 and -26% in the liver, 
      35 and -58% in the intestine). 3. To determine the mechanism(s) involved in the
      depression of hepatic CYP3A, infected mice were treated on day 7.5 post-infection
      with a monoclonal antibody raised against interferon-gamma (anti-IFN-gamma, or
      from days 7.5 to 10 post-infection with either N(G)-monomethyl-L-arginine (NMMA),
      an inhibitor of reactive nitrogen intermediates (RNI) production, or N
      acetylcysteine (NAC), a reactive oxygen intermediates (ROI) scavenger. 4. Total
      CYP content was restored in the liver of infected mice treated with anti-IFN
      gamma, but with marked interindividual variability. NAC treatment led to a
      recovery in the liver of total CYP content (+35 %), CYP3A content (total
      recovery), and the rates of Ery (+59%) and CyA (+87%) metabolism, whereas
      inconsistent results were obtained with NMMA. These results suggest that NAC, but
      probably not NMMA, partially protects hepatic CYP3A from Toxoplasma-mediated
      suppression in mouse.

PMID- 9173680
TI  - Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by
      cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations.
AB  - 1. Interethnic differences in cytochrome P4502A6 (CYP2A6) levels and coumarin 7
      hydroxylation activities were determined in liver microsomes of 30 Japanese and
      30 Caucasians. 2. Although CYP2A6 levels and coumarin 7-hydroxylation activities
      varied very significantly in the 60 human samples examined, both CYP2A6 levels
      and coumarin 7hydroxylation activities were found to be higher in Caucasian than
      Japanese population. 3. Interestingly, eight of the 30 Japanese examined showed
      very low or undetectable levels of coumarin 7-hydroxylation activities as well as
      of CYP2A6 in liver microsomes. All of the Caucasians, however, had significant
      CYP2A6 levels and variable 7-hydroxylation activities. 4. Kinetic analvsis of
      coumarin 7-hydroxylation activities in liver microsomes of various human samples
      suggested that although there were  260-fold differences in Vmax's in 10 human
      samples examined, the Km's were very similar (2.1 + or - 107 mu M); a value
      consistent with that obtained (1.2 mu M) with purified CYP2A6 in reconstituted
      system. 5. The results suggest that CYP2A6 is actually involved in the 7
      hydroxylation of coumarin in human liver microsomes, and that interethnic
      differences in coumarin 7-hydroxylation activities in Japanese and Caucasian
      population may be ascribed to the differences in expression of CYP2A6 protein.

PMID- 9173681
TI  - Role of cytochrome b5 in the oxidative metabolism of polychlorinated biphenyls
      catalyzed by cytochrome P450.
AB  - 1. The role of cytochrome b5 in the cytochrome P450-dependent hydroxylation of
      tetrachlorobiphenyl (TCB) isomers was examined using a reconstituted system
      consisting of CYP2B1 and CYP1A1 and rat liver microsomes. 2. By addition of
      cytochrome b5 to the reconstituted system containing CYP2B1, the 3-hydroxylation
      of 2,5,2,'5'- and 2,5,3',4'-TCB was increased about six-fold, but the 3- and 5
      hydroxylation of 2,4,3',4'-TCB was decreased by about 50% 3. All hydroxylations
      of 3 ,4,3',4'-,2,5, 3,4'- and 2,4,3',4'-TCBs were decreased by addition of
      cytochrome b5 to the reconstituted system containing CYPlA1. 4. In stoichiometry
      measurements, changes in NADPH oxidation and coupling efficiency by addition of
      cytochrome b5 was observed and these differed according to the position of
      chlorine atoms of TCBs and cytochrome P450 isoforms used in the systems.

PMID- 9173682
TI  - Liver haem metabolism in adjuvant-induced arthritic rats.
AB  - 1. Adjuvant-induced arthritic (AA) rats show a striking decrease in the level of
      cytochrome P450, a key microsomal haemoprotein involved in electron transport and
      drug metabolism in the liver. In the present study, we examined the relationship
      between the reduction of P450 content and haem metabolism in the liver of AA
      rats. 2. The activities of many enzymes catalyzing the biosynthesis of haem in
      the liver were significantly higher in AA rats than in normal rats, whereas only
      coproporphyrinogen oxidase activity in AA rats was markedly lower than that in
      normal rats. Furthermore, the activity of haem oxygenase, a key enzyme in the
      haem degradative pathway, increased significantly in AA rats. In addition, the
      degree of increase in the activity of this enzyme was clearly higher than that in
      the activity of 5-aminolevulinate synthase, a key enzyme in the haem synthetic
      pathway. 3. These results suggest that the reduction of live P450 content in AA
      rats is based on the lowering of liver haem content due to the combined action of
      the increased haem oxygenase activity and the decreased coproporphyrinogen
      oxidase activity. The changes in these enzyme activities were apparently
      suppressed by the continuous administration of indomethacin, which improved the
      arthritic states of the animals.

PMID- 9173683
TI  - Reductive activation of 1,1-dichloro-1-fluoroethane (HCFC-141b) by phenobarbital-
      and pyridine-induced rat liver microsomal cytochrome P450.
AB  - 1. During anaerobic reductive incubation of liver microsomes, from either the
      pyridine- or phenobarbital-treated rat, with 1,1-dichloro-1-fluoroethane (HCFC
      141b) in the presence of a NADPH-regenerating system, a time- and dose-dependent
      formation of reactive metabolites was detected as indicated by a depletion of
      added exogenous glutathione. 2. A statistically significant, dose-dependent loss
      of both cytochrome P450 and microsomal haem was also observed under these
      experimental conditions. Furthermore, a statistically significant decrease of p
      nitrophenol hydroxylase and pentoxyresorufin O-depentylase activity was measured
      in microsomes from the pyridine- and phenobarbital-induced rat, respectively
      indicating that both P4502E1 and P4502B undergo substrate-dependent inactivation.
      3. Both reactive metabolite formation and P450 inactivation were almost
      completely inhibited by previous bubbling of the incubation mixture with carbon
      monoxide, indicating that interaction of the substrate with a free and reduced
      P450 haem iron is required for substrate bioactivation and enzyme loss. 4. The
      presence in the incubation mixture of the spin-trap N-t-butyl-alpha-phenylnitrone
      (PBN) and the carbene trap 2,3-dimethyl-2-butene (DMB) largely prevented both
      glutathione depletion and P450 loss. This suggests that free radical and carbene
      intermediates formed by the metabolic activation of the substrate are involved in
      the inactivation of P450 and the loss of its prosthetic haem group.

PMID- 9173684
TI  - Interspecies differences in coumarin metabolism in liver microsomes examined by
      capillary electrophoresis.
AB  - 1. A simple, rapid method was developed for studying xenobiotic metabolism by
      cytochrome P450 in liver microsome preparations. Capillary electrophoresis was
      used to separate the metabolite from the metabolic mixture. 2. Coumarin is
      metabolized to 7-hydroxycoumarin by a cytochrome P450 isoenzyme. Human, bovine,
      gerbil, mouse (Schofield, CO1), rat, rabbit, porcine, and cynomologus monkey
      microsomal preparations were investigated for coumarin metabolism by determining
      the content of 7-hydroxycoumarin present after metabolism. 3. Separation of 7
      hydroxycoumarin from the reaction mixture was carried out in 50 mM phosphate
      buffer, pH 6.8, on a fused silica capillary at 25 degrees C and 15 kV. The
      metabolic matrix consisted of an NADPH regeneration system, 205.5 mu M coumarin,
      and the microsomal preparation. Standard curves were prepared in the microsomal
      preparation and the limit of quantification was 6.17 mu M, with a linear range
      from 0 to 308.5 mu M. 4. The reaction was initiated by the addition of the
      microsomes. An aliquot of the reaction mixture was removed at specific timed
      intervals over 2 h and injected directly onto a capillary electrophoresis column
      and the concentration of 7-hydroxycoumarin determined. The metabolism of coumarin
      to 7-hydroxycoumarin is greatest in human and monkey microsomes.

PMID- 9173685
TI  - Study of coumarin metabolism by Chinese hamster lung fibroblasts expressing a
      human cytochrome P450 using H-nmr.
AB  - 1. Human cytochrome P450 2A6 is expressed in Chinese hamster lung fibroblasts.
      The isozyme hydroxylates coumarin at the 7-position. 2. Metabolism of coumarin in
      these lung fibroblasts was monitored using 1H-nmr. Media samples were taken from
      cells grown in flasks and also in a fluidized bed bioreactor. In each case 7
      hydroxycoumarin was readily observable by nmr in crude extracts of the medium. 3.
      The rate of formation of 7-hydroxycoumarin observed in the acute bioreactor
      experiments on a per cell basis was found to be much higher than that obtained
      under chronic monolayer conditions, and correlated with glucose consumption
      rates.

PMID- 9173686
TI  - Pharmacokinetics and metabolism of zamifenacin in mouse, rat, dog and man.
AB  - 1. Zamifenacin was rapidly metabolized in vitro by liver microsomes from rat,
      dog, and man. 2. Zamifenacin exhibited extensive plasma protein binding with
      human plasma showing 20 and 10-fold higher binding that that in rat and dog
      respectively. 3. Following oral administration to animals, metabolic clearance
      resulted in decreased bioavailability due to first-pass metabolism in rat and
      mouse. Oral clearance in man was low as a result of increased metabolic stability
      and increased plasma protein binding compared with animals. 4. Metabolism was the
      major route of clearance of zamifenacin with the primary metabolic step resulting
      in opening of the methylenedioxy ring to yield the catechol. In man, this
      metabolite was excreted as the glucuronide conjugate, whereas in the animal
      species it was further metabolized by mono-methylation of the catechol.

PMID- 9173687
TI  - [Helicobacter pylori: pretherapeutic resistance status in Germany (Ruhr area)].
AB  - BASIC PROBLEM AND OBJECTIVE OF STUDY: The situation of pretherapeutical
      antimicrobial drug resistance of Helicobacter pylori has therapeutical
      implications. For this reason the present study was designed to evaluate the
      frequency of resistance in Germany. MATERIAL AND METHODS: A total of 201 H.
      pylori isolates cultured on the basis of biopsies taken by routine gastroscopies
      were tested for resistance by E-test. The antibiotics examined were amoxicillin,
      tetracycline, clarithromycin and metronidazole. For further analysis the last 101
      patients were asked for demographical and clinical data that were evaluated for a
      correlation with metronidazole resistance. RESULTS: Pretherapeutical resistance
      against amoxicillin and tetracycline was not detected. The rate of drug
      resistance against clarithromycin came to 3% and against metronidazole to 29%.
      There was a higher incidence of metronidazole resistance in female patients (Odds
      ratio 1.71; p = n.s.). Reliable predictors for metronidazole resistance, however,
      could not be identified. CONCLUSIONS: About 30% of H. pylori isolates are
      pretherapeutically resistant to metronidazole. Resistance to clarithromycin is
      still rare, but further monitoring remains necessary to detect changes in the
      community.

PMID- 9173688
TI  - [Massive hemorrhage from jejunal varices].
AB  - A 21-year-old male presented with melaena and signs of hemorrhagic shock. In the
      following days several episodes of hematochezia occurred requiring the
      transfusion of nine units of blood. Findings at gastroscopy were normal, at
      colonoscopy fresh blood was noted from the ileocecal valve. Angiography performed
      in a bleeding-free interval showed no abnormalities. At repeat angiography,
      bleeding (from a left lateral branch of the superior mesenteric artery) was
      provoked by instillation of plasminogen activator. Subsequently, hemostasis was
      achieved by superselective embolization using coils. At operation one week later,
      a polypoid tumor of 1 cm diameter was resected along with a 4 cm segment of
      adjacent jejunum (40 cm distal to the ligament of Treitz). Histologically, a
      jejunal varix with superficial ulceration was diagnosed.

PMID- 9173689
TI  - [Acute hemolytic crisis as the initial manifestation of Wilson disease].
AB  - A 25-year-old woman who had delivered a normal child after a normal pregnancy
      four months ago, was suffering from a common cold. The latter was treated by
      tetracyclines. A few days later she developed an acute severe hemolysis. Moreover
      she had signs of hepatic failure which was characterized by a considerably
      reduced synthetic capacity of the liver but low serum aminotransferase levels and
      a proximal renal tubular disorder. With a negative Coombs test an autoimmune
      hemolytic anemia was unlikely. Therefore diagnostic procedures were directed at
      the cause of the liver injury. An increased urinary excretion of copper, strongly
      elevated levels of liver tissue copper and the detection of a Kayser-Fleischer
      ring by slit-lamp examination proved the diagnosis of Wilson's disease-presenting
      clinically only as severe hemolysis. Ceruloplasmin concentration in serum was in
      low normal range and not diagnostic.

PMID- 9173690
TI  - [Intestinal intercellular tight junctions. I. Structure and molecular mechanisms
      of regulation].
AB  - The existence of tight junctions between epithelial cells has been known for over
      100 years, but their exact functions remained elusive until recently. The present
      paper summarizes the newest knowledge about morphology, molecular components and
      regulation of tight junctions. In the chapter about morphology the criteria for
      classification of epithelia as well as the importance of the "freeze fracture"
      electron-microscopic technique in forming our present ideas about the fine
      structure of tight junctions will be discussed. The two existing theories about
      the molecular composition of the resistance-forming barrier ("lipid-model" and
      "protein-model", resp.) and the important properties of the tight-junction
      associated proteins characterized in the past years are discussed in the chapter
      about molecular components. Finally, in the last part of the paper the factors
      playing an important role in the regulation of tight junctions, including the
      cytoskeleton, the protein kinases A and C, the phospholipase C and two categories
      of the GTP-binding proteins are reviewed.

PMID- 9173691
TI  - [Adjuvant combined radiochemotherapy of rectum carcinoma with long-term 5
      fluorouracil infusion].

PMID- 9173692
TI  - [Postprandial gallbladder function: not only unidirectional emptying?].

PMID- 9173693
TI  - [Long-term follow-up of HBeAg-positive patients after interferon-alpha treatment
      for chronic hepatitis B].

PMID- 9173694
TI  - [Combined therapy with transvenous cardioverter/defibrillator and anti
      bradycardia pacemaker systems].
AB  - Implantable cardioverter/ defibrillators (ICD) represent in many patients with
      ventricular tachyarrhythmias the first line treatment. Up to 15% of the patients
      requiring an ICD need concomitant permanent cardiac pacing for bradyarrhythmias
      resulting in the need of simultaneous ICD- and antibradycardic pacemaker-therapy.
      We present four patients with successful implantation of a transvenous ICD-system
      (Medtronic Jewel 7220 and Micro Jewel 7221; electrode: Medtronic 6939), all of
      which had an antibradycardic pacemaker (2 unipolar, 2 bipolar) implanted prior to
      ICD-implantation. Meticulous intraoperative testing in order to avoid adverse
      interactions between the two systems has been carried out successfully in all
      cases. Possible adverse interactions comprise oversensing of pacemaker signals by
      the ICD with subsequent inadequate therapy, inhibition of defibrillation therapy
      during ventricular fibrillation caused by false detection of pacemaker spikes by
      the ICD as well as reprogramming of the pacemaker after shock delivery. A review
      of the published literature yielded 91 reported cases of combined ICD- and
      pacemaker-therapy. In 16% of the patients, one or more of the mentioned
      complications have been observed. Those occurred more frequently with unipolar
      than with bipolar pacemaker-systems. Thus, combined therapy with antibradycardic
      pacemaker and transvenous ICD-systems can be performed safely.

PMID- 9173695
TI  - [Non-transmural anterior wall infarct: changes in myocardial energy metabolism in
      remaining vital myocardium].
AB  - To characterize energy metabolism in vivo after nontransmural anterior myocardial
      infarction, patients (group A, n = 19) with a stenosis of left anterior
      descending artery (LAD) and anterior wall hypokinesia by levocardiography were
      examined by phosphorus magnetic resonance spectroscopy (MRS). Spectra were
      compared to those of healthy volunteers (n = 15). The volume of interest was
      placed into the anterior myocardial wall by magnetic resonance imaging.
      Phosphorus spectra were recorded under optimal antiischemic medication. To
      separate the influence of coronary stenosis from that of the ischemic insult,
      additional patients (group B, n = 4) with LAD-stenosis but without left
      ventricular dysfunction were examined. The effect of antiischemic medication on
      the phosphorus spectra was evaluated in patient group C (n = 4), who had the same
      clinical features as group A. In these patients, MRS was first performed without
      antiischemic medication (washout period > one day) and then repeated during
      intravenous application of glyceroltrinitrate (GTN). Mean PCr/ATP-ratio was
      significantly lower in group A patients (1.24 +/- 0.18) than in healthy
      volunteers (1.74 +/- 0.23; p < 0.01 unpaired t-test). Patients with normal left
      ventricular function (group B) showed PCr/ATP-ratios (1.64 +/- 0.22) similar to
      those of normal controls (p = 0.23). After GTN infusion PCr/ATP-ratio of group C
      rose from 1.12 +/- 0.08 to 1.32 +/- 0.13 (p < 0.01 paired t-test). Thus,
      hypokinetic myocardium after nontransmural infarction is characterized by a
      larger decrease of the cellular energy buffer PCr compared to the myocardial ATP
      content. These findings may reflect degenerative changes of myocytes due to
      disturbed microperfusion in viable areas of the infarct or remodeling processes
      of viable myocytes in the infarct region. Both mechanisms may lead to adaptive
      changes of cellular enzyme concentrations resulting in a reduced PCr content of
      the myocytes.

PMID- 9173696
TI  - [Noninvasive coronary angiography with electron beam tomography: methods and
      clinical evaluation in post-PTCA follow-up].
AB  - Electron beam tomography (EBT) is a computed tomography technique with unique
      spatial and temporal resolution. The aim of the study was to establish and
      evaluate a protocol for the non-invasive visualization and detection of stenoses
      of the coronary arteries. Following phantom studies, 103 patients were
      investigated. Among these, 25 patients after coronary angioplasty (PTCA) were
      included in a prospective, blinded comparison to coronary angiography. After
      injection of contrast agent in a peripheral vein, 40 axial cross sections of the
      heart were acquired, triggered to the ECG (slice thickness 3 mm, 1 mm overlap,
      pixel size 0.29 x 0.29 mm). Three-dimensional reconstructions of the heart and
      coronary arteries were performed in the form of "shaded surface display," the
      results were compared to coronary angiography. In the reconstructions, the
      proximal and mid section of the LAD was visualized in 94% and 85%, image quality
      was reduced for the right coronary artery (89%/64%) and left circumflex
      (74%/54%), mainly due to movement artifacts. EBT displayed a sensitivity of 100%
      (9/9) for the detection of occlusions and high-grade restenoses in patients after
      PTCA, due to one false-positive result, specificity was 92% (12/13). Three PTCA
      patients could not be evaluated due to respiration artifacts. Contrast-enhanced
      electron beam tomography (EBT) permits the visualization of coronary arteries and
      the detection of stenoses and occlusions with high sensitivity and specificity.

PMID- 9173697
TI  - [Quantitative tissue Doppler echocardiography in comparison with M-mode
      measurements in healthy probands].
AB  - Quantitative tissue Doppler echocardiography is a new diagnostic approach to left
      ventricular systolic performance. The aim of the present study was to validate a
      recently developed method based on the computer software TDI-Labor enabling a
      variable time and space related measurement of regional wall velocity from tissue
      Doppler images. Therefore, in 63 volunteers the mean velocity of a 2 mm thick
      subendocardial slice during the systolic ejection period was determined from
      frozen tissue Doppler M-mode images of the left ventricular posterior wall
      obtained using the left parasternal window. The same images were employed for
      comparative measurement of the mean endocardial velocity using the conventional M
      mode slope approach. Tissue Doppler data of the subendocardial wall velocity were
      found to correspond closely to the mean endocardial wall velocity (y = 0.97x +
      0.17; r = 0.77; p < 0.0001). The average wall motion gradient of the population
      was 1.33 +/- 0.35. Wall motion velocity and wall motion gradient were shown to be
      not age dependent. The new software approach to an improved analysis of wall
      motion offering any sized sample volumes and time intervals for wall velocity
      measurements can be regarded as an exact and easily feasible method. Further
      clinical and experimental investigations are needed to evaluate its diagnostic
      relevance to the detection of ischemia and other myocardial dysfunction.

PMID- 9173698
TI  - [Intracoronary ultrasound changes the therapeutic approach in ambivalent
      angiography findings].
AB  - Despite careful evaluation of multiple projections, coronary angiography may give
      ambiguous results of lesion severity. The purpose of this study was to analyze
      the impact of ultrasound imaging on revascularization treatment strategy in
      angiographically ambiguous findings. We reviewed our experience with such
      equivocal angiographic findings before intervention in 31 patients (34 lesions)
      who had additional intravascular ultrasound (IVUS) to clarify coronary anatomy.
      Intervention was felt to be indicated if area stenosis by IVUS exceeded 50% in
      the left main or 75% in other major coronary arteries. To evaluate the clinical
      efficacy of IVUS based management strategies, all patients had clinical follow-up
      after 1 year. Seven of nine ostial lesions were overestimated by angiography, but
      two of three left main lesions were found to be significant. Seven lesions in one
      of the proximal coronary arteries whose significance was difficult to judge by
      angiography were found not to be significant by IVUS, whereas in the other four
      severe obstruction was confirmed. Membranes by angiography corresponded to
      remnants of ruptured plaques by IVUS in all five patients. However, significant
      narrowing was found in only two patients. Side branch ostial lesions were ruled
      out by IVUS in all four instances. Two patients with unstable angina but normal
      angiograms showed complex atherosclerotic plaques in the left coronary artery.
      IVUS led to a change of therapy in 21 patients (revascularization instead of
      conservative treatment in two and cancellation of initially intended intervention
      in 19). At follow-up examination, 17 of these 21 patients were free of cardiac
      symptoms. Interventions at the site thought not severely diseased by IVUS had to
      be performed in two patients with persistent angina who were afterwards free of
      symptoms. One patient with persistent chest pain had a second coronary angiogram
      during the follow-up period, but conservative therapy was continued. Evaluation
      was impossible in one patient because of bypass surgery due to another coronary
      lesion. In conclusion, IVUS was clinically useful in patients with
      angiographically ambiguous findings and resulted in a change of therapy in 21/31
      patients obviating interventions in 19 patients with excellent clinical results.

PMID- 9173699
TI  - [Stents: new studies--new trends].
AB  - The increasing frequency of stent implantation into coronary arteries is based
      mainly on assumptions. One of these assumptions is that stents may prevent
      restenosis. Stents can prevent restenosis as has been shown in two randomized
      studies (Stress I and Benestent I), but only in large (> 3.0 mm) vessels with
      short denovo lesions. Despite the very tight selection of patients suitable for
      stent implantation in these two studies, the advantage for stents remained small
      (about 10% less restenosis) and appeared to decrease with time following
      intervention. There is increasing concern about the extension of stenting in an
      "unrestricted strategy". This concern was expressed in the ACC Expert Consensus
      Document which was published recently (JACC 28, No 3, September 1996: 782-794).
      Based on lack of data for most of the presently used stent indications the expert
      group recommended a more selective strategy for the implantation of stents into
      coronary arteries.

PMID- 9173700
TI  - [Aerosolized prostacyclin for preoperative evaluation and post-cardiosurgical
      treatment of patients with pulmonary hypertension].
AB  - BACKGROUND: Inhaled nitric oxide (NO) has been shown to selectively lower
      pulmonary vascular resistance and is applied in patients with pulmonary
      hypertension (PHT). However, application and monitoring is complex and not always
      successful ("non-responders"). We evaluated the effect of aerolized prostacyclin
      (aePGI2) as a therapeutic alternate to NO. PATIENTS AND METHODS: aePGI2 and NO
      were applied to patients with different causes of pulmonary hypertension (Group
      1a: preoperative patients with intracardiac shunting defects and Eisenmenger's
      disease, n = 30; Group 1b: patients with primary or postoperative PHT, n = 13;
      Group 2: PHT immediately following surgery for congenital heart disease, n = 6).
      RESULTS: Pulmonary vascular resistance could be lowered significantly (Group 1a:
      from 91% of systemic vascular resistance to 58% with NO and 53% with aePGI2;
      Group 1b: from 20.2 Wood Units*m2 to 13.4 and 11.3; Group 2: from 24.9 Wood
      Units*m2 to 9.5 and 10.5); cardiac index increased (Group 1b: from 2.96 to 3.55
      and 3.96 l/min*m2, Group 2: from 1.57 to 1.89 and 2.00 l/min*m2). CONCLUSIONS:
      The short-term application of aePGI2 shows a selective pulmonary vasodilation
      similar to NO. Given adequate monitoring, aePGI2 appears to be useful for the
      acute treatment of PHT.

PMID- 9173701
TI  - [Frequency of atrial pacing in patients with intermittent atrial fibrillation and
      2nd or 3rd degree atrioventricular block. Thera DR Pacemaker Study Group].
AB  - Patients with 2nd or 3rd degree AV-block and paroxysmal atrial fibrillation could
      be suitable for VDDR pacemakers, if they are not or rarely paced in the atrium.
      We studied in 23 of these patients 1 month after DDDR pacemaker implantation, how
      often they were paced in the atrium with usual pacemaker programmings; patients
      with < 10% atrial pacing were compared with patients with > or = 10% atrial
      pacing. In case automatic mode switch was programmed, the number of mode switch
      episodes was assessed as a marker for the frequency of atrial tachyarrhythmias.
      Atrial pacing < 10% of the time occurred in seven, pacing from 10 to 19% in six,
      from 20 to 29% in two, and > or = 30% of the time in eight patients. Five of the
      seven patients with < 10% atrial pacing were paced in the DDD mode, but only four
      of 16 patients with > or = 10%. Usual clinical findings were unable to predict
      patients with rare atrial pacing. Patients with < 10% as well as with > or = 10%
      atrial pacing had < 10 mode switch episodes in 67% each. CONCLUSIONS: During
      short-term follow-up after DDDR pacemaker implantation 30% of the patients with
      paroxysmal atrial fibrillation and second or third degree AV-block, with present
      usual pacemaker programmings, rarely had atrial pacing, that means < 10% of the
      time. These patients would be probably suitable for VDDR pacemakers. Rare atrial
      pacing had no influence on the occurrence of automatic mode switch episodes.

PMID- 9173702
TI  - [High incidence of isolator fractures in transvenous implantation of cardioverter
      defibrillators].
AB  - With the growing complexity of transvenous ICD-lead systems the incidence of lead
      complications might increase in comparison to usual pacemaker leads. The
      incidence of insulation defects of transvenous leads was determined during a mean
      follow-up time of 23.8 +/- 10.9 months. Among 130 transvenous ICD-patients, eight
      insulation-breaks in seven patients (6%) could be identified after a mean follow
      up of 28 +/- 13 months. After a follow-up period of 12 months no lead defect was
      identified, after 24 months 96.3 +/- 1.8% of all transvenous leads were free of
      complications, after 36 months 87.9 +/- 6% and after 48 months in 61.2 +/- 18.7%
      of all leads no isolator fracture was found. In seven cases an operative revision
      was required. All insulation-defects were exclusively found in abdominally
      implanted silicone lead-systems type Endotak/CPI (Cardiac Pacemakers, Inc., USA):
      isolator fractures occurred in 12% of all Endotak leads used, 19% of the Endotak
      C models 62, 64, 72 and 74 were affected. In none of 66 implanted Transvene lead
      systems (Medtronic, Inc., USA) were isolator defects found. In six patients the
      proximal part of the sensing lead near the device was affected. All of these
      patients experienced potentially harmful repetitive device discharges. In one
      patient during elective ICD-replacement an isolation break of the proximal shock
      electrode was found, in another patient between the proximal and distal shock
      electrode. Despite regular follow-ups with impedance-measurements, only in one
      case was the insulation break foreseeable. Stored electrograms were helpful to
      disclose insulation defects. With increasing age of the transvenous lead systems
      a growing number of insulation defects has to be expected. Especially the
      isolators of the first Endotak C models 60-74 seem to create major problems with
      increasing age.

PMID- 9173703
TI  - [Atrial sensing and atrioventricular synchrony in single lead VDD pacemakers. Can
      the appearance of atrial undersensing be predicted?].
AB  - Single-lead VDD-pacing is an alternative to DDD-systems in patients with AV-block
      and normal sinus node function. Atrial sensing plays a central role in these
      pacemakers. AV-synchrony, incidence of atrial arrhythmias and the occurrence of
      sinus node disease were investigated in 108 patients with VDD-pacemakers followed
      over a mean period of 24.8 months after implantation. Determinants influencing
      the occurrence of atrial undersensing were especially focused on. Mean atrial
      potential and sensing threshold were reduced within the first 2 weeks after
      implantation (p < 0.01). Intermittent atrial undersensing occurred in 25.9% of
      patients and was observed in 82.1% of these patients within the first 2 weeks
      after implantation. Positioning the atrial dipole in the low right atrium showed
      a significantly higher incidence of atrial undersensing (42% in comparison to 24%
      in the other positions). In a multivariate analysis including intra- and
      postoperative measurements as well as characteristics of the pacemakers and
      leads, it was the only parameter significantly (p < 0.02) correlated to the
      occurrence of atrial undersensing. Atrial fibrillation was observed in 4.6% of
      patients, a sinus node disease became evident in 2.7% of patients; 92.6% of
      patients remained in the AV-synchronous mode. Intermittent atrial undersensing is
      common in single-lead VDD-pacemakers and difficult to provide during
      implantation. The atrial dipole should not be positioned in the low right atrium
      and highest atrial sensitivity should generally be programmed. Nevertheless, VDD
      pacing achieves an AV-synchrony comparable to DDD-pacemakers.

PMID- 9173704
TI  - [Transmyocardial laser revascularization--morphologic, pathophysiologic and
      historical principles of indirect revascularization of the heart muscle].
AB  - Under normal conditions the coronary system of the human heart is not
      hermetically isolated from the surrounding structures nor the ventricles, but is
      in various ways connected to the adjacent arteries and the cardiac chambers.
      These natural connections have been models for most surgical efforts to
      revascularize the myocardium. Numerous anastomoses between the aorta and the
      coronary branches functionally resemble aorto-coronary bypass grafts. Coronaro
      ventricular anastomoses do also exist in the myocardium and therefore
      transmyocardial laser revascularization should allow blood to penetrate from the
      ventricle into the myocardium. This process should not be called "reptilization"
      of the human heart, as in large reptilian hearts the nutrition of an extensive
      amount of myocardium only by diffusion is highly unlikely. Transmyocardial laser
      revascularization results in a relevant reduction of clinical symptoms and an
      increase of exercise capacity in approximately two thirds of the patients
      treated. Objective data of enhanced myocardial perfusion as assessed by positron
      emission tomography and stress echocardiography has up to now only been presented
      by smaller studies. Open laser channels are rarely visualized by conventional
      ventriculography for the limited resolution of the technique. Possibly contrast
      echocardiography may offer a more appropriate option to proof the systolic
      filling of the laser channels, as recently reported in patients. This would allow
      a correlation between clinically successful revascularization and functioning
      channels in contrast to an early or late failure due to the closure of the
      channels. As to the current opinion, transmyocardial laser revascularization is
      no alternative to established medical, interventional or surgical therapies but
      may in conjunction with bypass surgery or as a sole procedure offer a new option
      for those patients, who were recently considered to be refractory to conventional
      treatment. Experimental studies in particular should contribute to the
      understanding of therapeutic mechanisms and lead to standardized indications in
      the surgical treatment of end-stage coronary heart disease. Even though in
      transmyocardial laser revascularization the perioperative risk depends mainly on
      the degree of cardiac disease and the overall state of the patient, and impaired
      left ventricular function is per se no exclusion criterium, if viable myocardium
      is detectable. Many questions concerning indications, long-term prognosis and
      pathophysiological mechanisms are still open to discussion and have to be
      answered in order to find standardized applications for treatment of end-stage
      coronary artery disease.

PMID- 9173705
TI  - [Problems in carrying out baroreflex sensitivity measurements in clinical routine
      practice: practicability and complications].
AB  - Measurement of baroreflex sensitivity is a new method to identify patients after
      myocardial infarction with a high risk for sudden cardiac death, ventricular
      tachycardia or ventricular fibrillation. In this retrospective study the
      baroreflex sensitivity was obtained noninvasively by measuring the systolic blood
      pressure blood pressure with a FINAPRES-device and correlating this with the R-R
      intervals of the ECG after raising blood pressure with an intravenous dose of
      Norfenefrin-hydrochloride (Novadral). According to other investigators a
      correlation of > 0.7 with a significance of p < 0.05 was recommended for
      evaluable results with a baroreflex sensitivity < 3 ms/mm Hg being judged as
      decreased. We investigated 302 patients (mean age 59 +/- 17 years, 224 males, 78
      females). 75% of the investigations showed acceptable results. In 77 cases (25%)
      reasonable results could not be achieved. We found premature ventricular beats to
      be responsible in 18 investigations (6% of all investigations). 41 (13.1%) of all
      investigations were not evaluable because of bad correlation for unknown reason.
      When we looked closely at these nonevaluable results, we found a significantly
      higher number of patients with impaired left ventricular ejection fraction (<
      40%), diabetes or inducible sustained ventricular tachyarrhythmia in the
      electrophysiologic study in this group. During all investigations no severe side
      effects were observed. We conclude that the noninvasive measuring of the
      baroreflex sensitivity is a save method and leads to reasonable results in 75% of
      the investigations. In 13.1% it is not possible for unknown reason to achieve
      sufficiently correlating values. These measurements cannot be evaluated from
      nowadays' standards and have to be further investigated as they may indicate a
      population at high risk.

PMID- 9173706
TI  - [Transmyocardial laser revascularization--a treatment option for coronary heart
      disease?].
AB  - Transmyocardial laser revascularization (TMR) is a new therapeutic principle for
      patients with coronary artery disease and no possibility of conventional
      revascularization with CABG or PTCA. The clinical value of the method is not
      known. Therefore we investigated all 46 patients treated with sole TMR in our
      center using clinical investigation, LV and coronary angiography, right heart
      catheterization, MIBI perfusion imaging and myocardial FDG-PET pre- and 6 months
      post TMR. 117 patients judged not suitable for conventional revascularization
      procedures were submitted for TMR. The indication for the procedure was
      reevaluated in every case. 52 patients (mean EF 41 +/- 16%) could be further
      treated by intensified anti-anginal medication, seven patients received bypass
      grafts, four patients had PTCA, three patients were listed for heart
      transplantation, and five patients had a combined CABG plus TMR. Only 46 (38% of
      the submitted patients, mean EF 55 +/- 15%) were accepted for sole TMR. CCS class
      of these patients was 3.3 +/- 0.4, mean age was 63.6 +/- 7.3 years, 70% were
      males. The postoperative mortality within 30 days was 5/46 (10.8%); 9/46 patients
      (19.5%) suffered from perioperative myocardial infarction. Other complications
      were ventricular fibrillation in two cases on the second postoperative day and a
      rupture of the spleen on the 14th postoperative day. 8/46 patients (17%) had
      wound infections. Survivors showed an improvement in their CCS class (1.9, 2.1,
      1.9 after 3, 6 and 12 months, respectively, mean observation time 0.61 +/- 0.4
      years). These patients were able to perform bicycle stress tests significantly
      longer (98 s +/- 9 pre versus 120 +/- 13 s post TMR, p = 0.01). Angiographic EF
      fell from 57.8% +/- 15% to 52.6% +/- 19% (p = 0.02) and the number of hypokinetic
      chords rose from 23.6 +/- 20.9% to 30.6 +/- 24.1% per patient (p = 0.008),
      predominantly in the inferior wall. Nuclear studies showed reduced myocardial
      perfusion and vitality after TMR. Four patients in the TMR group had
      reintervention (PTCA) because of progression of coronary sclerosis of native
      vessels. One patient had mitral valve replacement due to severe regurgitation.
      Kaplan-Meier analysis showed no significant difference in survival between the
      TMR and the medical group when stratified according to initial ejection fraction.
      Sudden death and congestive heart failure are the most important causes of
      mortality. Our data show that TMR improves symptoms and exercise performance of
      otherwise not treatable patients with diffuse coronary artery disease. Due to a
      lack of an improvement of cardiac perfusion, function or prognosis TMR should be
      used only in highly selected cases when conventional methods fail to improve
      patients symptoms.

PMID- 9173707
TI  - [Successful treatment of fulminant myocarditis with the biventricular MEDOS
      Assist System (MEDOS HIA-VAD)].
AB  - BACKGROUND: Successful weaning from biventricular mechanical support with full
      recovery of the myocardial function is extremely rare in fulminant myocarditis.
      We report on our experience with the new MEDOS HIA ventricular assist device.
      METHODS AND RESULTS: We used the MEDOS assist system to support a 30-year-old
      woman with profound circulatory impairment caused by acute myocarditis. The
      device provided adequate hemodynamics and recovery of myocardial function.
      Despite anticoagulation therapy we had to change either the left or right
      ventricular pump chamber because of clot formation on the surface of the outflow
      tract. On the 14th postoperative day a surgical reintervention was necessary for
      bleeding from the cannulation site of the pulmonary artery. After 17 days the
      myocardial function had recovered and we could remove the assist system. The
      following parameters were measured before implantation of the MEDOS assist system
      and after weaning from circulatory support: ejection fraction 15 vs. 45%, cardiac
      index 0.7 vs. 2.6 L/min/m2, arterial pressure (systolic/diastolic/mean) 81/55/66
      vs. 113/66/82 mm Hg, pulmonary artery pressure 33/25/29 vs. 34/20/28 mm Hg,
      pulmonary capillary wedge pressure 24 vs. 19 mm Hg. CONCLUSIONS: Despite severe
      cardiac failure in fulminant myocarditis requiring biventricular mechanical
      support full recovery of the myocardium is possible.

PMID- 9173708
TI  - [Effect of qualitative stenosis characteristics on the quality of measurements of
      various QCA systems].
AB  - Reproducibility and accuracy of in vitro measurements are very high using
      recently developed QCA systems. We analyzed the impact of lesion characteristics
      ad the image quality on the quality of measurements under clinical conditions.
      For the study we selected 57 coronary artery lesions which had a clinically
      relevant distribution for stenosis severity, lesion characteristics, and image
      quality. Every effort was made to eliminate procedural sources of error. Three
      investigators measured each lesion five times with each of three QCA systems
      (AWOS, Cardio and CMS). Only the measurements of the minimal stenosis diameter
      were analyzed. The precision of all the measurements was high with the AWOS (0.04
      mm), the Cardio (0.05 mm), and the CMS systems (0.06 mm). Variability of
      measurements increased for the following criteria: Ambrose-III morphology (CMS
      0.082 mm), surface irregularities (Cardio 0.069 mm, CMS 0.073 mm), TIMI I (Cardio
      0.084 mm, CMS 0.0121 mm), and moderate image quality (CMS 0.07 mm). There were no
      differences in the precision of the measurements in the other groups of lesion
      characteristics. There were no relevant differences in any of the measurements
      between the systems (AWOS-Cardio -0.07 mm, AWOS-CMS-0.11 mm, Cardio-CMS-0.04 mm).
      Smaller diameters were measured with the AWOS system than with the CMS and the
      Cardio systems when the lesion was calcified (AWOS-Cardio-0.109 mm, AWOS-CMS
      0.161 mm). This was only a trend, however, and did not reach statistical
      significance, which was also true for the other differences found between the
      systems according to various lesion characteristics. In summary, we found that
      the measurement quality of the QCA systems used in this study is not altered by
      the underlying lesion characteristics or the image quality.

PMID- 9173709
TI  - [Visual assessment or quantitative measurement of coronary stenoses: significance
      for "prima vista"-PTCA].
AB  - In 300 patients with 339 coronary lesions the percent diameter stenosis (%-DS)
      was assessed both by visual estimation and by digital quantitative coronary
      angiography (DQCA) by use of an on-line computer work-station. The decision for
      coronary angioplasty in the same setting ("prima vista"-PTCA) was based on
      history, evidence of ischemia and visual estimation of %-DS. DQCA measurements of
      the 339 stenoses revealed a normal distribution of lesion severity with a mean of
      58.4 +/- 11.3%. In contrast to DQCA visual estimation led to a bimodal
      distribution with a nadir at approximately 55% between two peaks at approximately
      45% and approximately 75% and a mean of 70.5 +/- 19.6%. Visual estimation
      underestimated lesions in the range of 30-55% and overestimated the %-DS between
      55-99%. Visual estimation revealed a %-DS > or = 60% in 251 stenoses (74.0%) of
      the 339 lesions, an estimate that led to subsequent "prima vista"-PTCA.
      Conversely, DQCA revealed only 184 stenoses (54.3%) with a %-DS > or = 60%; thus,
      86 stenoses (25.3%) did not meet the morphologic indication criteria for PTCA.
      The bimodal distribution of stenosis severity according to visual analysis with
      an overestimation of borderline stenosis severity reflects at tendency for "self
      referral" of patients for PTCA. DQCA serves as an objective tool in the decision
      making process for PTCA and may reduce "cosmetic" interventions or justify to
      defer PTCA. Especially in the selection process for "prima vista"-PTCA DQCA
      quantification of stenosis severity is recommended.

PMID- 9173710
TI  - [Chemoreflex and baroreflex sensitivity in patients with survived sudden cardiac
      death].
AB  - INTRODUCTION: To evaluate patients with an increased risk of sudden cardiac death
      the analysis of ventricular late potentials, heart rate variability and
      baroreflexsensitivity is helpful. However, the prediction of malignant arrhythmic
      events cannot be performed with sufficient accuracy. For a better identification
      of high risk patients other methods are necessary. In this study the impact of
      the chemoreflexsensitivity for the prediction of ventricular tachyarrhythmias was
      investigated. METHODS: Out of 44 patients included in the study, 23 were
      survivors of sudden cardiac death (SCD). Seven patients suffered from sustained
      monomorphic ventricular tachycardias, 14 had no arrhythmic events in their prior
      history. For the investigation of the baroreflexsensitivity (BRS) systolic blood
      pressure was augmented by Norfenefrin (Novadral) and the resulting increase of RR
      intervals was measured in the surface-ECG. For determination of the
      chemoreflexsensitivity (ChRS) the ratio of the RR-interval-shift and the blood
      pressure shift during a 5-min inhalation of oxygen with a nose mask was formed.
      RESULTS: Patients with aborted SCD showed significantly decreased values for the
      ChRS compared to those patients without an arrhythmic event in their prior
      history (2.49 +/- 1.86 vs. 6.75 +/- 6.79 mm Hg, p < 0.001). In contrast, for the
      BRS no significant differences could be found (5.23 +/- 3.95 vs. 5.34 +/- 3.10 mm
      Hg, p = n.s.). Patients with aborted sudden cardiac death and inducible
      tachyarrhythmias during the electrophysiologic study showed significantly lower
      values of BRS and ChRS compared to patients without inducibility. CONCLUSION: As
      a new method for identification of patients with an increased risk of sudden
      cardiac death the analysis of chemoreflexsensitivity seems feasible and indicates
      an increased arrhythmic risk with a high sensitivity. The predictive impact has
      to be corroborated in larger patient collectives by prospect studies.

PMID- 9173711
TI  - [QT dispersion in surface ECG and QT dynamics in long-term ECG in patients with
      coronary heart disease in the chronic post-infarct stage with and without
      ventricular tachyarrhythmias--correlation with other risk parameters].
AB  - QT-dispersion (QTD) in 12-lead surface-ECG and QT-dynamics in Holter-ECG, defined
      as the time-course of the frequency corrected QT-interval (mQTc), were determined
      in 42 patients with coronary artery disease in chronic postinfarction stadium
      without ventricular tachyarrhythmias (CAD/VTA-) and in 24 CAD patients with
      ventricular tachyarrhythmias (CAD/VTA+). 14 healthy volunteers served as control
      group (CG). Correlations with hemodynamic data (LVEF, severity of CAD) and with
      other risk-parameters (ventricular late potentials, short-time heart rate
      variability) were calculated. QTD in CAD/VTA-was significantly higher compared to
      CG (48.4 ms+/- 19.6 vs 31.4 ms +/- 9.8, p < 0.05). There were no intergroup
      differences in QT-dynamics. CAD/VTA+ patients showed the highest QTD-values (59.5
      ms +/- 31.1, p < 0.05 compared to CG/CAD/VTA0) and a significantly altered QT
      dynamics compared to CG/CAD/VTA- (mQTc: 431.3 ms +/- 38.8 vs 400.8 ms +/- 25.5 vs
      406.3 ms +/- l0.6, p < 0.05). Only parameters of QTD were significantly
      correlated to severity of CAD (r = +0.41, p < 0.01) and to LVEF (r = 0.43, p <
      0.01). We did not find significant correlations between the parameters of QT
      dispersion/QT-dynamics among one another and to the risk-parameters. These
      results indicate that the QT-dispersion in CAD-patients also in chronic post
      infarction stadium is elevated and that CAD-patients with VTA are characterized
      by an altered QT-dynamics. Parameters of both methods are independent of other
      validated risk-parameters. So the measurement of QT-dispersion and QT-dynamics as
      markers of inhomogenous repolarization could contribute to an improvement of risk
      stratification of CAD-patients.

PMID- 9173712
TI  - [High frequency catheter ablation as therapy of symptomatic ventricular
      extrasystole].
AB  - Ventricular ectopic activity is commonly encountered in clinical practice.
      Usually it is not associated with life-threatening consequences in the absence of
      significant structural heart disease. However, frequent ventricular ectopic beats
      can be highly symptomatic and even incapacitating in some patients. Currently,
      reassurance and pharmacological therapy are the mainstays of treatment. This
      study assesses the useful role of catheter ablation in eliminating drug
      refractory monomorphic ventricular ectopic beats in severely symptomatic
      patients. Eight patients were included, five patients had no heart disease and in
      three patients a structural heart disease was present (coronary artery disease in
      1, hypertensive heart disease in 1, mitral valve prolaps in 1). The ejection
      fraction was higher than 40% in all patients (mean EF 56 +/- 14%). Mean number of
      ventricular ectopic activity was 29,295 +/- 10,650 VPB/24 h (1209 +/- 457 VPB/h)
      before ablation. No other spontaneous or induced arrhythmias were documented. The
      site of origin of ventricular ectopic activity was accurately mapped by using
      earliest endocardial activation time during ectopic activity or pace mapping, or
      both. The ectopic focus was located in the right ventricular outflow tract in
      five patients and in the left ventricle in three patients (posteroseptal 2,
      anterolateral 1). Frequent ventricular ectopic beats were successfully eliminated
      by catheter ablation in all patients. Early recurrence occurred in one patient
      after 10 min and 30 min after the procedure. In another patient a recurrence
      occurred 6 days after the procedure. In a second session he was successfully
      ablated and remained free of recurrence since 2 months. After ablation the mean
      number of ventricular premature beats was 211 +/- 159 VPB/24 h (9 +/- 7 VPB/h).
      The mean number of radiofrequency applications was 8 +/- 7 (range 2-22). Mean
      radiation time was 12 +/- 8 min. No complications were observed. During a mean
      follow-up of 6 months there were no further recurrences in the remaining six
      patients. Radiofrequency catheter ablation can be successfully used to eliminate
      monomorphic ventricular ectopic activity. It may therefore be a reasonable
      alternative for the treatment of severely symptomatic, drug resistant monomorphic
      ventricular ectopic activity.

PMID- 9173713
TI  - [Anatomic distribution, conduction properties and recurrences after ablation of
      multiple in comparison with single accessory conduction pathways].
AB  - In 1076 consecutive patients referred for radiofrequency current catheter
      ablation, the anatomical distribution and conduction properties of accessory
      pathways (APs) as well as the mode of recurrence after ablation were
      retrospectively analyzed and compared in patients with multiple and single APs.
      Except for 17 patients with Ebstein's anomaly, the prevalence of patients of
      multiple APs in this cohort was 5.4%. Patients with multiple APs. as opposed to
      patients with a single AP, had significantly more often APs located on the right
      free wall (23% versus 10%) and--since the prevalence of septal APs was identical
      in both groups--less frequently APs located on the left free wall (44% versus
      56%). Also, concealed APs were significantly more often encountered in patients
      with multiple APs (45% versus 24%). Recurrence of conduction across an AP which
      had presumably been ablated was observed in both groups with statistically equal
      incidence of < 5%. In 11 patients with multiple APs, the additional AP was only
      found at the repeat session. These "new" APs were mostly concealed (9 out of 11)
      and necessitated an intervention predominantly late after the initial ablation
      session. Intermittent concealed conduction appears to be a likely explanation for
      this phenomenon. Patients with multiple APs exhibit a higher incidence of right
      free-wall and concealed APs, yet they stand the same, approximately 95%, chance
      of cure as do patients with a single AP. Nearly 25% percent of repeat sessions in
      patients initially thought to have a single AP are caused by the late
      manifestation of an additional AP.

PMID- 9173714
TI  - [Diagnostic value of different echo- and Doppler echocardiography methods in
      quantifying mitral valve stenoses].

PMID- 9173715
TI  - [Therapy refractory end stage angina pectoris in coronary heart disease--a
      clinical and scientific challenge].

PMID- 9173716
TI  - [Quality of life in advanced coronary heart disease].
AB  - The integration of aspects of health-related quality of life (QL) into diagnosis,
      therapy and rehabilitation of patients with advanced coronary artery disease
      (CAD), especially with therapy-resistant angina pectoris, is important for at
      least two reasons. First, restrictions in patients QL often confronts the
      treating cardiologist with problems which could be overcome by a more
      comprehensive, psychosocially oriented intervention approach. Secondly, reduced
      QL was shown to have a negative impact on the course of CAD and on survival. Both
      aspects are discussed with reference to current scientific evidence, including
      our own study on effects of a comprehensive lifestyle change on QL in CAD
      patients.

PMID- 9173717
TI  - [Transmyocardial revascularization].
AB  - Transmyocardial laser revascularization refers to the perfusion of the reptilian
      heart with its large ventriculo-myocardial channels and to well-known ventriculo
      coronary connections in congenital heart defects. By a high energy CO2-laser
      transmural channels can be created at a beating heart and may, by connecting to
      the intramyocardial capillary network or by inducing a neocapillarization,
      improve the blood supply to the ischemic myocardium. This indirect method of
      revascularization is indicated in symptomatic patients with diffuse coronary
      heart disease, not accessible by conventional methods like PTCA or coronary
      bypass surgery. Worldwide, this new kind of operation has already been performed
      in some 100 intractable patients. In our hospital 79 patients have been treated
      with this new technique, 37 of them in conjunction with conventional bypass
      surgery. The majority of those patients had already undergone one or two bypass
      operations. The perioperative mortality was 11.4% including three non cardiac
      events. Postoperative follow-up after 3 and 6 months showed among the
      reinvestigated patients a significant improvement concerning angina- (CCS) and
      clinical classification (NYHA). Scintigraphy after the same time period revealed
      an improvement of myocardial perfusion in 50% of the reinvestigated patients.
      These results as well as the international reports demonstrate a clinical
      efficacy of this new therapeutic approach in a selected group of severely
      diseased patients. Further objective data and also experimental studies have to
      confirm the role of this new method in the treatment of diffuse coronary heart
      disease.

PMID- 9173718
TI  - [Cardiomyopexy--current status of an indirect revascularization method].
AB  - From May 1993 to September 1995, six patients underwent a new myocardial
      revascularization procedure. These patients were not suitable for direct coronary
      artery surgery due to diffuse and peripheral coronary stenosis and severe angina
      pectoris (NYHA classes III-IV). Thus, indirect myocardial revascularization or
      cardiomyopexy was performed. This consists in the grafting of a free skeletal
      muscle flap onto the ischemic heart. After harvesting the musculus latissimus
      dorsi as a free flap, the graft was transplanted onto the heart. The arterial
      stump of the muscle flap artery was implanted directly into the aorta, venous
      flow was drained into the right atrium. There to four weeks after the
      intervention the patients were free from angina. Ischemic ST-segment changes
      appearing preoperatively at 50 W disappeared 8 weeks later even at a higher
      exercise tolerance. The two patients that underwent the intervention in 1993 and
      1994 are still free from angina. In the present work experimental and clinical
      experiences with indirect myocardial revascularization are summarized and
      discussed.

PMID- 9173719
TI  - [Cellular sequelae of myocardial ischemia].
AB  - The interruption of arterial oxygen delivery to the myocardium during myocardial
      ischemia leads to a breakdown in oxidative phosphorylation and to a temporary
      formation of energy-rich phosphates by anaerobic glycolysis. However, the
      accumulation of the produced metabolites NADH, lactate and H+ rapidly blocks the
      key enzymes of glycolysis, so that a sufficient content of ATP necessary for
      cellular functions can no longer be maintained. Further accumulation of metabolic
      endproducts induces direct cellular damage by mitochondrial swelling and Ca2+
      overload. The early contractile dysfunction can be attributed to a diminished
      intracellular Ca2+ release and to cellular acidosis. Furthermore, the cellular
      loss of K+ and anions influences the electrophysiological integrity, while the
      myocytic Ca2+ overload activates cellular proteases and lipases and blocks
      mitochondrial phosphorylation. In the later ischemic period an increased
      noradrenaline release from the cardiac sympathetic nerves leads to an increased
      adrenergic activation and promotes the occurrence of malignant arrhythmias. On
      the other hand, myocardial ischemia is able to induce specific, protective
      proteins. The transition from reversible to irreversible cellular injury is not
      yet clarified. There is discussion about an excessive loss of energy-rich
      phosphates and an accumulation of cytotoxic metabolites. The release of
      proteolytic enzymes and the osmotic cellular swelling may cause an irreversible
      damage of the cellular membrane. At this time there are several approaches to
      limit ischemia-induced damage. Besides the established use of beta-blockers there
      are some beneficial perspectives for myocardial protection by blockade of the
      Na(+)-H(+)-exchange or by adenosine.

PMID- 9173720
TI  - [Coronary vasomotion in coronary heart disease--significance of epicardial and
      microcirculatory vessels for myocardial perfusion].
AB  - The most important function of the coronary vasculature is the effective
      regulation of coronary blood flow according to the metabolic needs of the
      myocardium. Under physiological conditions, coronary blood flow is regulated by a
      balance of vasoconstricting and -dilating components which can be differentiated
      with regard to the site (macro- vs. microcirculation), compartment (endothelium
      vs. vascular smooth muscle), and mechanism of action (receptor dependent vs.
      independent). This balance includes on the one hand the ability of the coronary
      circulation to maintain a relatively constant blood flow at any given oxygen
      demand irrespective of perfusion pressure (coronary autoregulation). On the other
      hand, coronary blood flow can be increased rapidly and effectively several-fold
      when myocardial oxygen demand increases. Previous investigations have
      demonstrated that the coronary endothelium plays a key role in the development of
      arteriosclerotic vascular lesions. In the time course of arteriosclerosis,
      functional alterations in endothelium dependent vasodilatation alterations are
      already present before angiographically demonstrable morphologic lesions. In the
      present manuscript, the diagnostic methods used to assess clinically the coronary
      macro- and microcirculation with regard to endothelium and smooth muscle
      dependent vasomotion are reviewed. In addition, present pharmacotherapeutic
      strategies to improve myocardial perfusion in coronary artery disease are
      discussed.

PMID- 9173721
TI  - [Effects of lipid lowering measures on coronary perfusion].
AB  - Secondary intervention trials in coronary heart disease have unequivocally proven
      the effectiveness of lipid-lowering medication in addition to dietary means.
      Orderly application of available drugs leads to reductions in LDL cholesterol and
      triglycerides accompanied by increases in HDL cholesterol. Specifically, LDL
      cholesterol lowering is associated with clinical benefits in coronary heart
      disease, it reduces the necessity of hospitalization and interventions, and leads
      to significant reductions in coronary as well as in overall mortality. Besides
      morphological changes of coronary vessels like regression or retarded progression
      of plaques, lipid-lowering was shown to normalize endothelial dysfunction
      associated with hyperlipidemia. Restoring endothelial function and improving
      coronary perfusion may be one of the factors responsible for the huge clinical
      benefits in secondary intervention trials as compared to the modest morphological
      changes. As the fact of lipid-lowering rather than the means by which it is
      achieved is of specific importance, dietary means have to precede and then
      accompany an eventual additional drug treatment.

PMID- 9173722
TI  - [Heparin-induced extracorporeal LDL precipitation (HELP) in therapy refractory
      hypercholesterolemia and coronary heart disease: effect on clinical and
      morphological regression of coronary sclerosis].
AB  - There are now several efficient and safe extracorporeal LDL eliminating
      procedures for the treatment of patients with familial hypercholesterolemia (FH)
      resistant to diet and combined drug therapy. In Germany, the most clinical
      experience is available from the heparin-induced extracorporeal LDL-precipitation
      (HELP) system. This procedure is additionally characterized by the effective
      elimination of not only LDL but also fibrinogen, a further independent risk
      factor of coronary heart disease CHD, which mainly influences blood flow
      characteristics. After 3-4 HELP treatments at weekly intervals, patients with CHD
      report markedly fewer episodes of angina pectoris, previously resistant to
      conventional therapy. This is probably related to a "functional regression" of
      CHD, which is due to the simultaneous lowering of LDL and fibrinogen, resulting
      in improved rheological properties followed by an increased oxygen supply to a
      previously insufficiently perfused myocardium. The restoration of endothelial
      function by maximal cholesterol lowering, as indirectly shown by changes in the
      cholesterol/phospholipid ratio in cellular membranes, obviously results in an
      improved vasomotoric response to endogenous vasodilatative substances, thus
      explaining the clinical improvement of our patients. As shown by a multicenter
      trial, regular long-term treatment with HELP is followed by an arrest of the
      atherosclerotic progression in 50% of the investigated segments. In 30% of the
      previously progressive segments, a significant regression was observed while only
      20% of the segments progressed. The mean degree of stenosis decreased by 4.3%.
      Regular HELP-LDL-/Fibrinogen apheresis in patients with severe CHD and angina
      pectoris refractory to conventional therapy results within a relatively short
      period in an improved coronary perfusion and long-term treatment induces
      regression of atherosclerotic coronary lesions.

PMID- 9173723
TI  - [Significance of coronary thrombosis for chronic myocardial ischemia].
AB  - Apart from the relevance of disorders of lipid metabolism for the clinical and
      morphological progression of coronary artery disease, coronary thrombosis has
      received increasing attention in recent years. It is undoubtedly the decisive
      factor in the pathogenesis of acute coronary syndromes, which is underlined by
      the therapeutic success of various antithrombotic interventions. Furthermore
      coronary thrombosis is regarded to be a key factor for morphological disease
      progression also in stable coronary syndromes, which eventually may lead to
      critical limitation of myocardial perfusion. This is caused by the formation of
      subclinical coronary thrombi, which either undergo endogenous lysis or become
      morphologically fixed as they are incorporated into the plaque. Besides local
      factors, systemic disturbances of hemostasis and endogenous thrombolysis are of
      relevance. The concept of thrombotic progression of coronary thrombosis is
      supported by data on the reduction of morphological disease progression or
      antiischemic effectiveness of anti-thrombotic interventions like aspirin, low
      molecular weight heparin and low-dose intermittent urokinase therapy.
      Percutaneous transluminal coronary angioplasty results in deep mechanical injury
      of the vessel wall, which is accompanied by secondary coronary thrombosis in the
      majority of the cases, not necessarily leading to abrupt vessel closure.
      Particularly, dilatation of primary thrombus as it has been described as the
      substrate of the culprit lesion in unstable coronary syndromes, promotes release
      of thrombin and activation of platelets, which in turn furthers the proliferative
      processes in the pathogenesis of restenosis. Even though data on the reduction of
      the rate of restenosis by the use of platelet aggregation inhibitors like
      aspirin, ticlopidin and dipyridamole have not consistently supported this
      concept, the EPIC. Study has shown that even in patients with stable angina
      pectoris clinical restenosis rate may be reduced by a platelet-IIb/IIIa
      antagonist.

PMID- 9173724
TI  - [Chronic intermittent urokinase therapy: anti-ischemic and hemodynamic effects].
AB  - Long-term intermittent urokinase therapy has been developed for patients with
      severe coronary artery disease and refractory angina pectoris. This therapeutic
      approach is predominantly effective at the microcirculatory level based on a
      combination of rheologic and fibrinolytic effects; furthermore, plaque regression
      seems to be a possible mechanism. Patients with refractory angina pectoris are
      characterized by severe coronary artery disease without a therapeutic option for
      conventional revascularization procedures, only slight impairment of left
      ventricular systolic function and hyperfibrinogenemia, which results in further
      enhancement of myocardial ischemia due to microcirculatory impairment of blood
      flow. In this article data on the anti-ischemic effectiveness as well as first
      results on the impact of this therapeutic approach on hemodynamics are described.
      A dose-response study, which compared 3 x 50,000 IU with 3 x 500,000 IU urokinase
      three times a week over a treatment period of 12 weeks demonstrated subjective as
      well as objective antiischemic effectiveness. Only patients who were treated with
      500,000 IU per injection achieved marked increases in exercise capacity, while
      some patients in the low-dose group presented even with a deterioration of
      exercise performance. First hemodynamic studies could not show marked changes of
      systolic parameters, either at rest or during exercise. But a decrease of
      pulmonary capillary wedge pressure at rest after treatment with 500,000 IU per
      injection indicates an improvement of diastolic function as a result of enhanced
      myocardial perfusion. Echocardiographic measurements of transmitral Doppler flow
      in 21 patients with end-stage coronary artery disease demonstrated normalization
      of early and late diastolic filling rates in most cases. These changes were
      accompanied by a reduction of clinical signs of heart failure. Long-term
      intermittent urokinase therapy is a valuable approach as it not only improves
      quality of life during the actual treatment period but by the persistence of
      therapeutic effects following the cessation of therapy.

PMID- 9173726
TI  - The Third International Feline Retrovirus Research Symposium.

PMID- 9173725
TI  - [Indications and limits of conventional revascularization methods in coronary
      heart disease].
AB  - The number of cardiologic patients undergoing invasive diagnostic catheterization
      is rapidly increasing. Due to more liberal and extensive indications for invasive
      diagnosis patients in relatively unfavorable clinical condition (e.g., elderly
      patients with severe extracardial disease, patients status post CABG) are being
      catheterized and, if suitable and indicated, undergo revascularization
      procedures. With rapidly increasing procedural skill of cardiovascular surgeons
      and invasive cardiologists even high-risk patients with severe coronary artery
      disease or underlying illness, who were classically excluded from surgical or
      catheter-invasive revascularization, are now being treated more aggressively. The
      changing indications for diagnostic catheterization and significant changes in
      the different modes of revascularization--operative bypass-surgery or
      interventional procedures--have led to continuous changes in the differential
      indications for these invasive therapeutic strategies. This article reviews and
      discusses the currently accepted indications for surgical and interventional
      revascularization as well as the limitations of these procedures.

PMID- 9173727
TI  - [The dynamic nature and age-related dependence of functional brain organization
      in attention].
AB  - Intrahemispheric functional organization was studied during a task expectancy
      period with special reference to attention mechanisms. The estimation of
      coherence of functionally identical rhythmic EEG components was made to
      characterize the intracortical integration. Several factors influencing the
      possibility to make an adequate prognosis and to realize it were varied.
      Different types of the task were used. Subjects of different age (7, 9-10 years,
      young adults) and children of the same age differing by the brain maturity level
      were under study. It was shown that all factors studied have certain influence on
      the brain organization underlying the task preceding attention. Clear age
      differences as well as the lag between the possibility to formation and
      realization the prognosis in children were observed. Alternative "strategies"
      used in different ages to facilitate the task performance were analysed;
      underlying mechanisms were discussed.

PMID- 9173728
TI  - [Information synthesis in key sections of the cortex as the basis of subjective
      experiences].
AB  - The main hypothesis developed in the paper proposes that the events of the
      subjective experience emerge as a result of the synthesis of three kinds of
      information in crucial for this mental function cortical areas. This information
      includes sensory one, information derived from memory and one coming from
      motivational centers. The hypothesis is based on researches of the brain
      mechanisms of perception and thinking. It has been shown that the sensation
      emerges as a result of the synthesis of information on physical parameters and of
      significance of the stimulus in the projection cortex neurons. This synthesis is
      provided by the circular spreading of the nerve impulses from the projection
      cortex to associative cortex, then to hippocampus and the hypothalamic motivation
      centers with the subsequent return of the impulsation to the projection cortex.
      It have been shown also that at thinking operations the cortical connections
      converge to define centers named the interaction foci. Their topography is
      specific for particular thinking operations. Thus in imaginative thinking the
      foci are located in temporo-parietal and in abstract-verbal thinking--in frontal
      cortex. It is proposed that the confrontation and the synthesis of information in
      the interaction foci result in decision making. The last part of the paper
      concerns the functional role of the subjective events and their possible
      influence on brain processes.

PMID- 9173729
TI  - [Brain biopotential mapping in emotional and cognitive pathology].
AB  - The EEG rhythms spectral power and intracortical connections were studied in
      depressive and schizophrenic patients in four schematically outlined main
      cortical quadrants. In depressive patients two cortical quadrants--right anterior
      and left posterior ones appeared to be predominantly involved in negative
      emotions regulation. Alpha-rhythm spectral power and cortical connections in
      these areas were decreased, pointing to their relative hyperactivation and
      functional disturbances. Schizophrenics patients were divided into two groups-
      with the predominance of "positive" and "negative" symptoms. In the first group
      there was revealed the decrease of the most EEG rhythms spectral power only in
      parietal areas, on the second one--in all cortical areas. There was also the
      significant alpha-rhythm spectral power asymmetry, different in the two groups of
      schizophrenic patients. In "positive" schizophrenics the decrease of alpha-rhythm
      spectral power was revealed in parietal and occipital areas of the right
      hemisphere, and in "negative" ones--vice versa, these results pointing of the
      relatively higher activation of the right posterior quadrant in the former group
      and of the left posterior quadrant in the latter one. In the anterior cortical
      quadrants the intracortical connections were however higher in the left
      hemisphere in "positive" and in the right one--in "negative" schizophrenics.
      Thus, there are some contradictory results obtained by different methods in
      anterior and posterior cortical quadrants in each hemisphere, these results being
      of opposite directions in patients with "positive" and "negative" manifestations.
      "Region of interest" (ROI) in schizophrenics appeared to be predominantly the
      frontal and temporal ones, while the "Rhythm of interest"--beta2.

PMID- 9173730
TI  - [Patterns in the shaping and realization of individual experience].
AB  - This article describes the methodological approach of systemic psychology. In the
      framework of this approach a wide range of experimental data is analyzed: results
      of neuronal recordings in vitro and in awake normal and pathological animals
      learning to perform and performing both complex instrumental and simple
      behavioral acts. Another block of analyzed data is based on the experiments with
      human subjects that learn and perform the tasks of categorization of words and
      operator tasks, subjects, performing group game activity and answering the
      questionnaires of psychodiagnostic methods. As a result of this analysis, the
      system psychology approach is used to describe qualitatively and quantitatively
      the formation and realization of individual experience.

PMID- 9173732
TI  - [The concept of reinforcement in research on simple nervous systems].
AB  - Analysis of applicability of the reinforcement concept to the learning studies in
      invertebrate systems is performed basing on literature and own data. It is
      suggested that reinforcement can be regarded not as an independent phenomenon,
      but as a state of the nervous system which precedes a long-term changes of
      behavior. Such consideration of reinforcement allows to use this concept in
      studies of plasticity and learning in simple nervous systems, investigate
      neurochemical mechanisms of reinforcement.

PMID- 9173731
TI  - [The molecular scenarios of the consolidation of long-term memory].
AB  - Long-term memory consolidation is a critical event in the transition of short
      lasting experiences into durable modifications of behaviour. Present article
      focuses on the problem of molecular bases of this process. It starts with a brief
      review of biochemical and pharmacological data demonstrating a universal
      dependence of long-term memory on gene expression in the brain. Some of the
      experimental studies of immediate early gene expression in the brain during
      learning are described in the second part of the article. A hypothesis is
      discussed according to which consolidation of long-term memory employ the same
      biphasic molecular cascade of gene expression that is used for cell growth and
      differentiation during development.

PMID- 9173733
TI  - [The high-frequency electroencephalogram: the results and outlook].
AB  - At present, the significance of high-frequency (HF) components in brain
      electrical activity (EA) is widely discussed in literature. In particular, the
      gamma range of human EEG is considered as one of the indices of cognitive
      activity. In the paper a review is presented of the author's own data concerning
      the functional estimation of low-voltage HF components of the neocortical EA
      recorded in the broad band (1-100, 1-256 Hz) in the course of instrumental
      conditioning in dogs. Three different techniques of EA analysis were used in the
      study: 1) fast Fourier transformation (FFT) of EA in a broad band, 2) developed
      by us alternative method of non-harmonic expansion of the EEG curves taking into
      account their shape, 3) factor analysis of the EA spectral densities. Combination
      of these techniques allowed us to obtain some novel evidence indicative of high
      informativity of the HF fluctuations. Spatial cortical localization of the HF
      components of the EA is much more expressed in comparison with the traditional 1
      30 Hz range. Results of factor analysis suggest functional heterogeneity of the
      HF band. Obtained data open new ways for researches concerning the phenomena of
      the functional mosaics in the neocortex as one of fundamental mechanisms in brain
      activity organization.

PMID- 9173734
TI  - [Sensory information--an important factor in ontogeny].
AB  - Ontogenetic process reveals a row of consecutive stages characterized by the
      gradual increase in complexity and by the changing specificity of sensory
      mechanisms basic for the adaptive behavior of the young. The study examines the
      mechanisms of interaction among different sensory systems during the formation of
      early behavioral patterns and analyzes why, at a certain stage of development, a
      particular sensory stimulus loses its efficacy in the organization of a given
      behavior and is substituted by another one, previously ineffective. A special
      attention is paid to formation of behavior based on sensory information within
      the limits of ontogenetically fixed developmental critical periods and to the
      role of the early sensory experience in learning in adult animals.

PMID- 9173735
TI  - [The comparative neurobiology of human and animal color vision].
AB  - Discrimination of colours was studied using instrumental learning paradigm in
      monkeys (Macaque rhesus) and fishes (Carpio Cyprinus L.). The confusion matrices
      composed of probabilities of instrumental responses were treated by factor
      analysis. The spherical structure of perceptual colour space revealed in both
      animals was close to one in humans. Four eigenvectors constituting four
      dimensional Euclidean hyperspheres correspond to red-green, blue-yellow, bright
      and dark neuronal channels.

PMID- 9173736
TI  - [The brain mechanisms of emotions].
AB  - At the 23rd International Congress of Physiological Sciences (Tokyo, 1965) the
      results of experiment brought us to a conclusion that emotions were determined by
      the actual need and estimation of probability (possibility) of its satisfaction.
      Low probability of need satisfaction leads to negative emotions actively
      minimized by the subject. Increased probability of satisfaction, as compared to
      the earlier forecast, generates positive emotions which the subject tries to
      maximize, that is to enhance, to prolong, to repeat. We named our concept the
      Need-Informational Theory of Emotions. According to this theory, motivation,
      emotion and estimation of probability have different neuromorphological
      substrate. Activating by motivatiogenic structures of the hypothalamus the
      frontal parts of neocortex orients the behavior to signals with a high
      probability of their reinforcement. At the same time the hippocampus is necessary
      for reactions to signals of low probability events, which is typical for
      emotionally excited brain. By comparison of motivational excitation with
      available stimuli or their engrams the amygdala selects a dominant motivation,
      destined to be satisfied in the first instance. In the cases of classical
      conditioning and escape reaction the reinforcement was related to involvement of
      the negative emotion's hypothalamic neurons while in the course of avoidance
      reaction the positive emotion's neurons being involved. The role of the left and
      right frontal neocortex in the appearance of positive or negative emotions
      depends on this informational (cognitive) functions.

PMID- 9173737
TI  - [The biochemical correlates of the individual typological characteristics of rat
      behavior].
AB  - The review of data (results of the authors' investigations and data from the
      literature) concerning neurochemical correlates of individual behavior in rats is
      presented. The "emotional resonance" test was used for behavioral selection of
      rats. Individual behavior in this test is related to the differences in free
      radical mediated processes, membrane lipid content, nitric oxide synthase
      activity and cAMP pattern in cerebral macrostructures. Behavior-related
      differences were revealed in intact animals, and in response to environmental
      factors. These differences depend on age; they may be global or specific for
      selected brain regions and/or related to interhemispheric lateralization of
      biochemical parameters.

PMID- 9173738
TI  - [Motor cortex functions in the reorganization of postural coordinations].
AB  - A well-known function of the motor cortex (MCx) is control of the limb distal
      musculature, in particular, isolated finger movements during precise and fine
      hand movements. However, MCx has another function connected with the motor
      learning process, namely, a suppression of synergies and coordinations
      interfering with a movement being elaborated. This was shown for various limb
      movements. However, majority of movements is accompanied by postural adjustment
      as well. Two experimental models of rearrangement of an innate pattern of the
      postural adjustment were developed, and MCx was shown during such kind of
      learning to suppress the activity of structures providing the innate postural
      patterns. In contrast to the control of limb movements, the MCx influences were
      found to be bilateral for the postural pattern reorganization. It was revealed
      recently, however, that a possibility of recovery for the sequential MCx lesions
      depends on the sequence of the lesions, so, perhaps the role of MCx of different
      hemispheres in the compensation is different.

PMID- 9173739
TI  - [Serotonin in genetically determined types of defensive behavior].
AB  - A review of the data concerning the role of 5-hydroxytriptamine (5HT) in
      genetically defined defensive behavior. 5HT-ergic system of the brain is involved
      in the expression of the genetic predisposition of rodents to defensive behavior-
      both aggression and freezing. The results suggest that the density of 5HT1A
      receptors in the frontal cortex is related to the expression of aggressive
      behavior of both types, while functional state of the brain 5HT system is
      involved in mechanisms determining the strategy of choice of type of defensive
      behavior--freezing or aggression.

PMID- 9173740
TI  - [The role of the interaction of serotonin- and noradrenergic systems in
      regulating behavior].
AB  - A review of the data concerning the role of 5-hydroxytriptamine (5HT)-ergic and
      noradrenergic (NA) system in the regulation of behavior. Reciprocal effects of
      cerebral 5HT-ergic and NA-ergic systems on brain morphogenesis and on behavior
      suggest that normal brain ontogenesis is mediated by the steady state of 5HT and
      NA. The disbalance between 5HT-ergic and NA-ergic systems in brain structures
      results in abnormal brain development and behavioral pathologies. The concept of
      reciprocal effects of 5HT-ergic and NA-ergic brain systems may serve as a basis
      for new principles of pharmacological correction of pathologies resulting from
      inborn or acquired disbalance of monoaminergic systems.

PMID- 9173741
TI  - [Volume transmission as a means of interneuronal interaction in the striatum].
AB  - This review of literature and own data is devoted to a special mode of
      intercellular communication in the GNS--volume transmission, that is based on
      diffusion of neuromediators from points of release through the brain
      extracellular space to distant non-synaptic receptor sites. Using the main
      neurotransmitters of the striatum (dopamine, glutamate and GABA) as an example,
      the author has analysed the evidence for the existence of volume transmission in
      this brain region, the tentative mechanisms underlying this mode for information
      processing, and receptors involved. Much attention has been paid to functional
      significance of volume transmission in the striatum for maintenance of behaviour,
      operated by this brain area.

PMID- 9173742
TI  - [The general principles of synaptic plasticity in the neocortex, hippocampus and
      cerebellum].
AB  - The unitary model of synaptic plasticity for the neocortical, hippocampal and
      cerebellar Purkinje cells is proposed. The model is based on the new modification
      rules. It was assumed that the necessary conditions for synaptic modifications
      are: the coincidence of pre- and postsynaptic cells activity (Hebbian rule) and
      the change of pre- and/or postsynaptic cell activity during the time that is
      sufficient for the shift of the ratio between protein kinases and protein
      phosphatases in postsynaptic cell. According to the suggested model similar
      mechanisms underlie homo-, hetero- and associative LTP and LTD of excitatory and
      inhibitory synaptic transmission. The involvement of cAMP and cGMP in synaptic
      plasticity of neocortical/hippocampal and Purkinje cells, correspondingly, may
      underlie the different Ca(2+)-dependent modification rules in these structures.
      The model is used for the analysis of stimulation parameters influence on the
      direction of synaptic modification. It is shown that stimulation frequency (Ca2+
      rise) necessary for LTP or LTD induction is relative but not absolute.

PMID- 9173743
TI  - [The cholinergic system of the striatum: its participation in the motor and
      sensory components of motor behavior].
AB  - This review deals with the recent data on participation of the dorsal striatum
      cholinergic system in orientation behavior and in regulation of attention to
      significant stimuli, which was realized via the range of subcortical structures,
      among them the intralaminar thalamic nuclei (CM-Pf) and pedunculopontine nuclei
      (PPN) play an especially important role. On the basis of our own experimental
      data it was suggested that by using an adequate pharmacological effects upon
      striatal cholinergic system, it was possible to change the sensory and motor
      components of movement behavior. Whereas the unilateral microinjections of
      cholinergic receptor agonists lead to behavioral changes only on the day of
      injection, the bilateral injections change the formed type of the movement
      behavior for a long time. An important role of the dorsal striatal cholinergic
      system in switching and modulation of the indirect efferent pathway was
      substantiated. By this mechanism, inhibition of nonspecific sensory afferentation
      at different subcortical levels and an increase of significant sensory signals
      can take place. A manifestation of this mechanism can be the sharp improvements
      of differentiation of sensory stimuli after activation of the striatal
      cholinergic system. On the other hand, the cholinergic striatal limitation of
      movement activity (a decrease of locomotion, an increase of tonic component of
      movement and streamlining of posture) may be the important factors for making a
      decision in a difficult situation.

PMID- 9173745
TI  - [A nootropic adrenocorticotropin analog 4-10-semax (l5 years experience in its
      design and study)].
AB  - Semax is one of the rare analogues of regulatory peptides which underwent all
      stages from fundamental investigations to practical usage. It has been
      demonstrated that this peptide is capable to stimulate operative memory and
      attention, to increase resistance to hypoxia and to improve brain circulation in
      experimental animals and human beings over prolonged period (20-24 h after
      intranasal administration in doses 0.015-0.050 mg/kg). Semax significantly
      improves memory and attention in healthy men under extreme conditions of
      activities. Moreover at present semax is successfully used in treatment of
      patients with different diseases of CNS. In the majority of cases the peptide
      exhibited positive effects and in no case it produced negative side actions or
      complications connected with its administration. There is good reason to believe
      that medical potentialities of semax have not been exhausted and in future new
      possibilities of its usage will be revealed.

PMID- 9173744
TI  - [The participation of cerebral hypoxia in the pathogenesis of neuroses (a new
      concept)].
AB  - The data are presented concerning the state of vascular brain system during
      experimental neurosis in Wistar rats, the intricate cerebral hemodynamical
      disturbances, shifts in activity of the crucial enzymes of the mitochondrial
      respiratory chain, and activation of the lipid peroxidation processes. The
      positive results on treatment of the experimental and clinical neuroses with
      antioxidants which have antihypoxic properties are presented. Results on increase
      of resistance to stress in rats under the influence of negatively charged air
      ions with expressed antihypoxic are discussed. The general outline is given of
      the molecular neurochemical processes which accompany the development of neurotic
      diseases as well as of reversal of these processes due to the antioxidant
      therapy. The concept concerning the cerebral hypoxia in neuroses is based on the
      obtained evidence. This concept opens the principally novel pathogenetical
      approaches to treatment and prevention of these diseases.

PMID- 9173746
TI  - [Audiogenic epilepsy: a morphofunctional analysis].
AB  - The rats of K-M line with high level of convulsive readiness to sound stimuli
      were tested. It was established that systemic application of epileptogenic
      stimulus evoked the decrease of level of convulsive readiness. The phenomena of
      habituation and normalization of animal behavior were revealed. The
      intraperitoneal injection of inhibitory transmitter--GABA and taurine (separately
      or in mixture) blocked the convulsive seizures. The functional influence by KCl
      induced spreading depression in the cerebral cortex bilaterally impairs the
      inhibitory processes, but not the changes the form of epileptiform seizure. In
      neurophysiological experiments using microelectrophoresis technique it was shown
      that taurine as inhibitory agent is more effective when applied to dendritic
      layers II-III; GABA is more effective if it is applied on soma of cortical
      pyramidal cells. Using the electron microscopic methods, the following changes
      were observed during the clonic seizure: axo-dendritic and axo-spine synapses in
      rat auditory cortex were activated. After the habituation to the epileptogenic
      stimulus, some features evidencing the decrease of activity were observed in
      ultrastructure of synapses in layers II-III. In 2 days after that the majority of
      ultrastructural shifts were normalized. Role of calcium ions in generation of
      epileptic seizures and their depression as main factor of antiepileptic
      mechanisms is discussed.

PMID- 9173747
TI  - [Autoantibodies to glutamate receptor subtypes--markers of functional brain
      damage: their diagnostic significance for detecting paroxysmal activity and
      ischemia].
AB  - A new direction in diagnostics and the control of pharmacological treatment of
      brain disorders is discussed. Problems which are considered in the review have
      significance for understanding the neurochemical mechanisms of paroxysmal
      activity and brain ischemic stroke. The identification of autoantibodies for
      glutamate receptors, thought to be involved in these brain disorders, presents a
      new approach toward characterization of clinical states of individuals and could
      have a wide application for control of efficiency of pharmacological treatments.

PMID- 9173748
TI  - [Work disability work in the first year of chronic polyarthritis. A comparison
      with members of the legal health health insurance].
AB  - Even though sick-leave (SL) is a direct consequence of the reduction of work
      capacity due to the disease, this has not gained much attention in early
      rheumatoid arthritis (RA). Therefore, the occurrence and duration of SL (defined
      as the history of SL as certified by a physician) was determined in a cross
      sectional multicenter study of early RA (< or = 12 months duration) and compared
      to the members of the compulsory health insurance. One hundred and thirty four
      gainfully employed consecutive outpatients fulfilled > or = 4 of 7 ACR 1987
      criteria of RA: 85 females (63% of 134 patients), age 50 years (median), disease
      duration 7 months (median). SL due to RA occurred in 102 of 134 patients (76%).
      The duration of SL because of RA was 11 days per month (about one-third of the
      disease duration) in males and 8 days per months (one-quarter of the time since
      the onset of RA) in females. SL due to RA was five times longer than expected
      from controls. In addition to SL because of RA, SL due to other causes occurred
      with a similar duration as in controls. Already in the first year of RA the large
      proportion of patients with SL due to RA and the long SL duration indicate the
      extent of substantial handicap concerning gainful employment.

PMID- 9173749
TI  - [Manifestation of neuro-Behcet disease in cyclosporin A therapy].
AB  - Behcet's disease is a chronic inflammatory disorder characterized by the triad of
      oral and genital ulcers and ocular lesions. One of the most life-threatening
      manifestations results from involvement of the central nervous system, presenting
      as necrotising meningo-encephalitis, most typically affecting the brain stem,
      internal capsula and basal brain ganglia. We report on a young Caucasian mate
      with Behcet's disease (HLA B 51+) and recurrent uveitis, who presented with acute
      neurologic involvement under CyA therapy 5 years after first diagnosis. At the
      time of admission MRI showed two high intensity lesions in the brain stem on T1
      weighted images enhanced with Gd-DTPA, reflecting active inflammation. Shortly
      after admission the CyA treatment was stopped and a therapy with high dose
      steroids and chlorambucil, starting with a dose of 2 mg daily was initiated. This
      led to improvement of neurologic symptoms, also documented by brain stem evoked
      potentials and investigations of cerebrospinal fluid, as well as of ophtalmologic
      symptoms within few days of treatment. Steroids were reduced to a maintenance
      dose of 12 mg Prednyliden daily. The brain MRI taken 8 weeks after onset of
      chlorambucil treatment showed the same lesions in the brain stem, with low
      intensity in the T1 weighted images an no longer enhanced Gd-DTPA uptake.
      Chlorambucil dose was reduced to 2 mg every second day after 8 months. There was
      no exacerbation in the follow-up of 12 months. We conclude that a 6-week
      Chlorambucil therapy consisting of 2 mg/p.o./d led to remission of neurologic
      involvement firstly evolving under CyA-medication which suggests superiority of
      chlorambucil as a treatment modality in neurologic as well as ophtalmologic
      features of the disease.

PMID- 9173750
TI  - [Hyper-IgD-syndrome].
AB  - We report on a 6-year-old Romanian girl with recently diagnosed hyper-IgD
      syndrome. The leading symptom of this rare disease are periodic pyrexia, joint
      involvements (arthralgias/arthritis) and swollen lymph nodes. A permanent
      increase of alpha 1-acid glycoprotein fucosylation indicates persisting
      inflammation. Most important in differential diagnosis in familial Mediterranean
      fever. Therapy is merely supportive as yet, the long-term outlook seems good
      despite duration of the illness. CONCLUSION: the hyper-IgD-syndrome must be
      considered in cases of otherwise unexplained periodic fever.

PMID- 9173751
TI  - [Acupuncture in treatment of inflammatory rheumatic diseases].
AB  - Seventeen studies were examined with regard to efficacy and scientific quality of
      acupuncture in rheumatoid arthritis, spondarthropathy, lupus erythematosus, local
      and progressive systemic scleroderma. Acupuncture cannot be recommended for
      treatment of these diseases. By far, the most studies examined failed to show
      sufficient quality.

PMID- 9173752
TI  - ["From the history of thoracic surgery". Friedrich Trendelenburg, born 1844 in
      Berlin, died 1925. Assistant of v. Langenbeck. Director of the Rostock, Bonn and
      Leipzig University Surgical Clinics].

PMID- 9173753
TI  - [Incidental gallbladder carcinoma--a report of experiences after 1,200
      laparoscopic cholecystectomies].
AB  - Incidental carcinoma of the gallbladder can be found histologically in 1-2% of
      specimens after surgery of benign diseases of the hepatobiliary tract. We present
      our results of 7 cases of incidental gallbladder carcinoma in 1200 laparoscopic
      cholecystectomies. Surgical treatment and clinical outcome are reported. We tried
      to outline special items of this disease within the context of minimal-invasive
      surgery.

PMID- 9173754
TI  - [Changes in liver perfusion caused by transjugular intrahepatic stent shunt
      (TIPSS)].
AB  - PURPOSE: to demonstrate and document TIPSS-induced changes of the perfusion
      pattern of the liver with special reference to several rheologic, morphologic,
      functional and biochemical parameters. Our analysis was based on a study in 100
      consecutive cases. PATIENTS AND METHODS: Evaluation and assessment of the
      following parameters before and within a 30-day post TIPSS period: portosystemic
      gradient; morphologic delineation of the portal circulation; invasive
      scintigraphic determination of the portal perfusion fraction (PPF) and the total
      liver perfusion (GLP); transcatheter intraarterial flow change measurement; serum
      levels of albumin and bilirubin; assessment of hepatic encephalopathy by
      appropriate testing; assessment of recurrent variceal bleeding RESULTS: by TIPSS
      variceal filling was widely reduced; as assessed morphologically and
      rheologically portal liver perfusion was significantly reduced. However, there
      was immediate onset of compensated liver perfusion by increased arterial inflow.
      Total liver perfusion was not significantly altered. In TIPSS portal
      decompression was readily achieved with reduction of the portosystemic gradient
      from an average of 24 mmHg to 10.5 mmHg. In our series we could not demonstrate
      an increased incidence of hepatic encephalopathy during the 30-day post TIPSS
      period. Bilirubin levels were significantly increased after TIPSS from 2.45 to
      2.61 mg/dl (p = 0.0067), while albumin levels were not altered. Early mortality
      was 4% and early re-bleeding rate 3%, respectively. CONCLUSION: the concept of
      TIPSS represents an individually calibrated H-shunt. The significant reduction of
      post TIPSS portal perfusion appears to be compensated by increased arterial
      inflow. This is reflected by invasive flow measurement results and by the
      clinical results. Letality of TIPSS is low.

PMID- 9173755
TI  - [Atypical metastasis of stomach carcinoma].
AB  - We report a case of unusual metastases from a gastric cancer. In a 66 years old
      female with bone metastases a breast cancer was diagnosed. The patient was
      treated by ablative surgery and chemotherapy but died short time later. An
      autopsy was performed and showed a large signetring cell carcinoma of the
      stomach. Further a diffuse involvement of the spleen unknown until autopsy was
      diagnosed. Serial tissue sections of all metastatic localizations were made.
      Histopathology and immunostaining including oestroprogesterone receptors
      identified a gastric cancer as the primary malignancy. A review of the recent
      literature on breast metastases from gastrointestinal tumours, gastric metastases
      from breast cancer and the problem of second primary malignancies is given.
      Further we reviewed the occult metastatic spread of the spleen and the importance
      of splenectomy in case of total gastrectomy.

PMID- 9173757
TI  - [Modified Gilchrist bandage].

PMID- 9173756
TI  - [Monstrous recurrence of serous cystadenocarcinoma of the pancreas].
AB  - Serous cystadenoma of the pancreas is a rare benign tumor. The diagnostical
      management is easy, preoperative histological finding is difficult. The surgical
      relevance is revealed by the fact, that this tumor shows a high recurrence rate,
      especially if a complete resection is not feasible because of a difficult tumor
      localisation. The whole problematic nature of this disease is underlined by the
      following case report, which illustrates that in 5 years 4 surgical interventions
      because of recurrent symptoms were necessary. Each single operation improved
      quality of life for a different time period. First aim must be the radical
      resection of the tumor during primary operation, but this is not always possible
      because of unfavorable tumor localisation.

PMID- 9173758
TI  - [Development of surgery for breast carcinoma by Joseph Rotter].
AB  - Hundred years ago Joseph Rotter published his new method of operation for breast
      cancer, by which the rate of local recurrences significant was decreased. This
      radical mastectomy performed similarly by Halsted in Baltimore (USA) was the
      surgical standard of the breast cancer therapy for a long time and is still used
      in local advanced carcinoma until today.

PMID- 9173759
TI  - [Therapy of breast carcinoma].

PMID- 9173760
TI  - [Molecular genetics of hereditary breast carcinoma].
AB  - Breast cancer is the most common malignancy among women. Genetic predisposition
      is considered to account for 5-10% of all cases while the majority of these
      cancers are sporadic and caused by complex interactions of exogenous and
      endogenous factors. The inherited predisposition can be due to germline mutations
      in one of several cancer susceptibility genes. For high risk families the two
      most important genes are BRCA1 on chromosome 17q, which confers a high risk of
      both, breast and ovarian cancer and BRCA2 on chromosome 13 associated with high
      penetrance of breast cancer but lower risk of ovarian cancer. A high risk of
      breast cancer is conferred by mutations in the p53 tumor suppressor gene as part
      of the rare Li-Fraumeni-syndrome, and possibly also by the estrogen receptor
      gene. Other cancer genes associated with a less increased risk of breast cancer
      are the autosomal recessive ataxia telangiectasia (AT) gene and the HRAS1 gene.
      Germline mutations in BRCA1 and BRCA2 account for the majority of families with
      multiple cases of breast and/or ovarian cancer and also at least 10% of cases
      below the age of 40 years. Genetic testing for BRCA1 mutations is not generally
      recommended except for women with a strong family history. The aim for the
      management of familial breast cancer should be the establishment of
      interdisciplinary teams to cover genetic counseling, molecular analysis, onco
      surgical therapy, psychosocial support and clinical follow-up.

PMID- 9173761
TI  - [Current surgical therapy of breast carcinoma and subsequent requirements for
      histopathologic diagnosis].
AB  - An extensive histopathological diagnosis-in the best way with intraoperative
      frozen section-is the basis for the actual surgical therapy of the breast cancer.
      The surgical treatment of breast cancer depends on the specific histopathological
      subclassification, distance of the tumor from the resection margin and reference
      to multifocality or multicentricity are the data for the individual therapy.
      Depending on the age and the above named criteria the operative treatment of the
      breast cancer will not be simply the mastectomy and lymphadenectomy, there are
      more surgical possibilities.

PMID- 9173763
TI  - [Subcutaneous mastectomy].
AB  - The subcutaneous mastectomy (SM) which cannot be standardized is the possible
      treatment in a given indication especially to reduce the risk of cancer to a
      large extent-though only through experienced hands. Any re-operation often
      resulting from the complications of reconstructions through silicon prostheses
      can be more extensive than mamma-carcinoma therapy itself. The patient as well as
      the surgeon must be aware that the aesthetic result of the therapy is not the
      primary reason for the operation but the prevention or therapy of a life
      threatening disease. With this perspective in mind the high rate of complications
      with SM is an acceptable risk and may ensure a high degree of permanent tumor
      removal.

PMID- 9173762
TI  - [Breast preserving therapy of breast carcinoma: analysis of over 1,300 patients
      treated in the Basel region].
AB  - From 1977 to 1994 a total of 1329 breast cancer patients have been treated with
      breast conserving surgery in the region of Basel. This analysis is based on 832
      patients treated from 1977 to 1990 according to a prospective treatment protocol,
      which was adjusted only once (1985). In comparison with the most known
      international publications this analysis represents one of the greatest
      homogeneous series of breast conserving treatment. We observe an overall 5-year
      survival of 91% and a 10-year survival rate of 77%. 94% of the women remain
      locally recurrence free at 5 years and 86% at 10 years respectively. At 5 years,
      freedom of local recurrence totals to 97% in patients without (pN0) and to 89% in
      patients with tumor involvement of the axillary lymph nodes (pN+) (p = 0.00008),
      as well as to 96% for pT1 and 91% for pT2-tumors (p = 0.08328). In our analysis
      the R0-resection significantly influences local recurrence free survival.

PMID- 9173764
TI  - [Changes in radical surgery of breast carcinoma in the last 20 years].
AB  - The retrospective analysis of 383 female patients with breast cancer of all tumor
      stages from the department of surgery (323 patients since 1979) and the
      department of gynaecology (58 patients since 1993) shows the abandonment of the
      radical mastectomy according to Rotter-Halsted (116 patients until 1989),
      acceptance of the modified radical mastectomy (178 patients since 1979) and
      introduction and rise of the breast conserving operations (67 patients since
      1983). In 1992 there was an extension of breast conservation treatment from T1 N0
      to T2 N1-2 tumors (tumor diameter till 4 cm). Operation technique: 1. Circular
      incision above the tumor, 2. tumor excision in histologically healthy tissue, 3.
      lower axillary dissection (level I and II with > or = 10 lymph nodes), 4. no
      suture of the gland and drainage without suction, 5. postoperative computerised
      high energy radiotherapy of the conserved breast (Clinic of radiotherapy of the
      University of Leipzig). Because of the high operation risk a simple mastectomy
      without axillary dissection was performed in 22 of 383 patients. RESULTS: 3 of
      383 patients died = 0.78% postoperatively due to tumor independent complications.
      One local tumor recurrence was observed 6 years after breast conserving therapy
      in 25 patients operated until 1992. In 42 patients operated since 1993 a tumor
      recurrence did not occur so far. The 5-year-survival-rate in 153 patients of all
      tumor stages amounted to 64%, in node-negative patients 80.3%, in node positive
      patients 51.7%. RECOMMENDATIONS: Breast conservation will be always recommended
      if the relation between tumor diameter and breast volume permits a cosmetic
      attractive result.

PMID- 9173765
TI  - [Bone metastasis in breast carcinoma].
AB  - 113278891978 and 1988 278 patients with metastatic disease of breast cancer were
      treated at the Clinic of Radiotherapy of the University of Wurzburg. 192 of these
      patients developed skeletal metastases. Particularly the skeletal axis was
      affected. In 58.3 percent (162 patients) skeletal metastasis was the first
      metastasis. The median age of the patients was 62.5 years at time of diagnosis of
      skeletal metastasis. Median interval between primary diagnosis of breast cancer
      and diagnosis of skeletal metastasis was 2.9 years. Median survival of patients
      with skeletal metastasis was 1.7 years. Skeletal metastases could not worse
      survival time, if other metastases already existed. Because of the relatively
      good prognosis we have to improve and combine the local and systemic therapy.

PMID- 9173766
TI  - [Ultrasound and clinical studies of periventricular leukomalacia in high risk
      newborn infants. II. Perinatal risk factors].
AB  - The incidence of periventricular leukomalacia (PVL) in risk neonates was
      evaluated among 300 risk neonates in a prospective ultrasound study at the
      Pediatric Clinic of the Medical Faculty, University of Rostock. Perinatal risk
      factors for the development of PVL and gestational age were taken into
      consideration. Maternal infections during pregnancy were found to be a risk
      factor for development of PVL. A severe hyaline membrane disease was more
      frequently diagnosed in highly immature preterm neonates with postnatal PVL. The
      percentage of highly immature preterm neonates with postnatal PVL and severe
      hyaline membrane disease was higher in vaginal-born risk neonates. A correlation
      between 1-minute Apgar scores < or = 3 and postnatal PVL was found in more mature
      preterm neonates.

PMID- 9173767
TI  - [Weight discordance of the second twin: effect on perinatal morbidity and
      mortality. An 8-year analysis of 213 twin deliveries].
AB  - In this retrospective eight-years-study we examine factors to be considered
      responsible for higher perinatal mortality in twins, especially in twins with
      discordant body weight. As a main risk factor for this we find vaginal delivery,
      i.e. from a non-vertex position. Other additional reasons for the higher
      perinatal mortality of twins are prematurity (less than 34 weeks of gestation)
      and birthweight lower than 1500 grams. Early hospitalisation has a positive
      influence on that risk. The perinatal mortality in the second twin (6.7%) is
      twice as high as in the first twin. The highest perinatal mortality (17.6%),
      however, is in twins with discordant growth whereas the second twin had a higher
      birthweight at delivery (15% more than the first twin). In twins with discordant
      body weight cesarean section gives advantage to the second twin versus vaginal
      delivery from breech presentation.

PMID- 9173768
TI  - [Blind prophylactic antibiotic administration in premature rupture of fetal
      membranes].
AB  - In a retrospective study based on patients treated at the Department of
      Gynecology and Obstetrics of the University of Cologne during 1984-1993, we
      tested whether antepartal prophylactic application of antibiotics in patients
      with premature rupture of membranes (PROM) decreases the frequency of maternal or
      fetal infections. With raising intervals between PROM and birth exceeding 24
      hours, the frequency of maternal/fetal infections raised in the total study
      population (n = 940). The maternal infection rate increased from 4% to 11% and
      the frequency of fetal sepsis from 4% to 19% with a PROM to birth interval
      exceeding 24 hours. In the group of patients with prophylactic application of
      antibiotics the frequency of maternal or fetal infections was not lower than in
      the group without antibiotics. This holds true for the total study population as
      well as for subgroups with different gestational ages. In the total study
      population 12% of antibiotics-treated patients and 22% of their newborns had
      peripartal infections, whereas in the untreated population 3% of the mothers and
      4% of the newborns showed signs of infection. The prophylactic application of
      antibiotics raises significantly the latency period in combination with or
      without tocolysis in PROM during 25. and 37. week of gestation.

PMID- 9173769
TI  - [Pre-pathologic-pathologic cardiotocographic pattern in second stage of labor.
      Analysis of the incidence of acidosis and recommendations for fetal blood gas
      analysis].
AB  - Fetal heart rate (FHR) patterns from 746 consecutive, documented vaginal
      deliveries within a 1 year period were reported on using the Hammacher Score.
      Characteristic FHR patterns were described and the frequency of acidosis
      calculated. FHR score, the single FHR parameters, baseline (BL), floatingline
      (FL) and oscillation type (OT) and the acid-base balance of the neonate were
      submitted to a correlation analysis according to Spearman. FHR patterns reported
      as ominous (FHR score > or = 5) were observed in 25.9% and were associated with a
      frequency of acidosis (pHUA < or = 7.20) of 38.1% Suspicious fetal heart rate
      patterns (FHR score 3-4) were seen in 60%, here the frequency of acidosis was
      8.5%. With the inclusion of decelerations by the parameter FL an increased
      frequency of acidosis of 29% was registered only when 4 points were allocated.
      Total FHR score and the score parameter baseline (BL) correlated closest with the
      pH changes at the end of birth. Tachycardic FHR patterns showed the highest
      frequency of acidosis (55%) and ominous tracings (83%). The commonest FHR
      pattern, normocardia with decelerations (48%) exhibited only a low frequency of
      acidosis (8%) and ominous tracings (15%) with an average pH value of 7.27 +/-
      0.08. To prevent an unnecessary operative delivery in the presence of an ominous
      FHR finding, whether in the late first stage or early second stage when birth is
      not imminent, a fetal blood analysis should be carried out. With a suspiciously
      assessed fetal heart rate pattern the fetal blood analysis will only rarely
      reveal a severe acidosis (pHUA < or = 7.10).

PMID- 9173770
TI  - [Clinical experiences with Climen in peri- and postmenopausal women].
AB  - 42 women with signs of androgenization were treated with Climen in the peri- and
      postmenopause for a period longer than 12 months. The effect on most typical
      climacteric syndromes was comparable to other free available compounds.
      Concerning our patients, Climen was more effective than other compounds. In no
      case the withdrawal of Climen due to side-effects was necessary. Surprisingly an
      androgenetical loss of hair was stopped in 9 out of 10 cases. Climen widens
      essentially the therapeutical possibilities concerning hormone replacement in
      peri- and postmenopausal women and should not only be used in women with signs of
      androgenization.

PMID- 9173771
TI  - [Postmenopausal hormone substitution and its effects on the climacteric syndrome,
      body weight and blood pressure].
AB  - The effect of 0.6 mg conjugated equine estrogens in combination with sequential
      medrogestone (5 mg from day 11 to 21) on climacteric symptoms, blood pressure and
      weight were investigated in 46 postmenopausal women. The climacteric symptoms
      were quantified by a modified Kuppermann-Index. After a 3 months' treatment the
      index decreased from 20.58 to 8.47 (p < 0.001). 28 patients (65%) showed a 50%
      and more reduction of climacteric symptoms. 40 patients (93%) reported an
      improvement of their complaints. The body weight remained stable. One patient had
      to interrupt the treatment due to a cerebral ischemic disease (PRIND). The
      systolic blood pressure was decreased by 7% and the diastolic by 16% under
      treatment (p < 0.001). 11 patients with borderline or not treated hypertension
      returned to normal ranges. 3 of the 4 patients treated with antihypertensiva came
      off the medicines.

PMID- 9173772
TI  - [Primary carcinoma of Bartholin's glands with HPV 18 detection].
AB  - A primary carcinoma of the Bartholin's gland is a rarely type of vulva-carcinoma.
      The patients median age are 55 years and the etiology of the carcinoma are still
      unknown. Viral influences are discussed. Most frequent types of carcinomas of
      Bartholin's gland are those of squamous cells and adenocarcinomas. This article
      reports on a 55 year old patient with a primary carcinoma of Bartholin's gland.
      The human papillomavirus 18 was detected by a polymerase chain reaction. The
      correct diagnosis was delayed because of an initial misinterpretation of the
      carcinoma as a Bartholin cyst, marsupialization and bad healing of the wound. The
      patient underwent a radical vulvectomy with bilateral inguinofemoral
      lymphonodectomy in combination with radiation therapy.

PMID- 9173773
TI  - [Postpartum obturator nerve syndrome: case report and review of the nerve
      compression syndrome during pregnancy and delivery].
AB  - Compression of a peripheral nerve or nerve trunk can occur during pregnancy and
      delivery. The injury may be caused by the fetal head, the application of forceps,
      trauma or hematoma due to cesarean section, or improper positioning in leg
      holders. Often, no cause of the injury is found. The most common nerve
      compression syndromes during pregnancy and delivery are carpal tunnel syndrome,
      femoral neuropathy, and post partal foot drop. Obturator neuropathy, meralgia
      paraesthetica, tarsal tunnel syndrome, and syndrome of the rectus abdominis
      muscle occur less frequently. Symptoms, such as paraesthesia, pain and palsies
      not always attract the immediate attention of the physician. Sometimes they are
      misinterpreted as nervous complaints. Often, remission is reached at delivery. A
      case of obturator neuropathy after delivery is reported, and literature on
      clinical, pathophysiological and electrophysiological findings in maternal
      obstetric palsies is reviewed.

PMID- 9173774
TI  - Metallic microparticle formation using the needle-through-needle technique.

PMID- 9173775
TI  - Resistance to atracurium.

PMID- 9173776
TI  - In search of effective programs to address students' emotional distress and
      behavioral problems part III: student assessment of school-based support groups.
AB  - Emotional distress and behavioral problems are common in high schools. This
      report describes the efficacy of an in-school program based on participation in
      volunteer-facilitated peer support groups in addressing these problems. Two
      hundred and fifty students who experienced such problems participated in weekly
      50-minute peer support groups led by adult nonmental health professional
      volunteers. The students anonymously evaluated their progress and program
      acceptability using an instrument developed specifically to evaluate the group
      experience. Analysis of the evaluation of the 131 respondents documented the
      reliability of a proposed Self-Assessment Questionnaire which showed that
      participation led to improvement in school, interpersonal, and internal domains.
      The program was highly accepted and showed other signs of success: half of the
      alcohol and substance users reduced their intake, and 60% of those who considered
      dropping out of school continued their education. The results provide preliminary
      evidence that peer support groups show promise as an economical and well-accepted
      method for early recognition and management of emotional and behavioral problems
      in high schools. For some adolescents, these groups may be the only acceptable or
      available therapeutic modality.

PMID- 9173777
TI  - Time perceptions and time allocation preferences among adolescent boys and girls.
AB  - How time is allocated between competing directed and nondirected activities can
      greatly define persona and lifestyle objectives. The important process of
      learning about time and the consequences of its various uses begins in childhood
      and adolescence, and provides the foundation for later life. This study examines
      whether girls differ from boys with regard to certain directed and nondirected
      types of time allocation preferences. Lifestyle objectives related to personal
      development (spending time), material achievement (selling time), social
      acceptance (giving time), and passive entertainment (passing or killing time),
      are explored using a time allocation preference model that defines a person's
      time investment portfolio. This study extends recent research by psychologists,
      sociologists, and anthropologists regarding the allocation and perception of time
      by examining student time allocation preferences and their association with
      teacher-observed behaviors in school. It was found that adolescent girls, whether
      considered by their teachers to exhibit at-risk or normal behaviors, seem to be
      less inclined toward nondirected activities and more toward other-directed
      activities. Boys seem to be more inclined toward nondirected activities. Being at
      risk as a school behavioral classification, is particularly associated with a
      large amount of nondirected activities in boys and large amounts of other
      directed activities in girls.

PMID- 9173778
TI  - Adolescents becoming adults: attributes for adulthood.
AB  - The research literature identifying the end of adolescence and the onset of
      adulthood has focused on event-related factors (e.g., marriage, occupation),
      while ignoring cognitive-related factors (e.g., responsibility for one's self and
      making decisions). This study addresses both realms. Adolescents (N = 113, M age
      = 16.5 years) were surveyed to determine what they believed were the most
      important attributes for becoming adults, and at what age their adulthood began.
      The sample perceived that adult status occurred at a mean age of 17.4 years (SD =
      2.55) with 78.8% of the youth reporting that they were "adults." The majority of
      the sample identified cognitive factors as indicators of adulthood. Further
      analyses indicated that respondents who perceived that adulthood occurred at
      younger ages had higher levels of self-esteem. Implications of the consequences
      of adulthood attributes and beliefs for current and later life adjustment are
      discussed.

PMID- 9173779
TI  - Family processes as predictors of adolescents' preferences for ascribed sources
      of moral authority: a proposed model.
AB  - This paper develops a model of the family's role in the moralization of the
      adolescent. To achieve this aim, the Circumplex Model of Marital and Family
      Systems (Olson, Sprenkle, & Russell, 1979; Olson, 1983) provides the theoretical
      framework needed to identify levels of adaptability, cohesion, and communication
      within each family system. Once identified, these family processes are treated as
      possible predictors of certain moral preferences, in particular, the number and
      type of sources of moral authority held by the adolescent. The notion "source of
      moral authority" is based on Henry's (1983) reconceptualization of Kohlberg's
      stage theory of moral judgments. In light of this, a new measure, the Moral
      Authority Scale (MAS) has been developed to assess such adolescent preferences
      for different sources of moral authority. Overall, this unique approach
      identifies salient family processes as influencing adolescent moral reasoning by
      drawing together systems theory, cognitive developmental, and psychosocial
      approaches and generating testable predictions. In so doing, research needs and
      inadequacies of the current literature are highlighted and possible strategies to
      overcome such problems are explicated.

PMID- 9173780
TI  - The friendships of delinquents.
AB  - This article is a review of research concerning the friendships of delinquents
      and nondelinquents. Contrasting theories and corollary research have pointed to
      either the distinctiveness of delinquent friendships or to the commonality with
      normal friendships. On close examination, with exceptions due to methodological
      and sample features, the research has been more supportive of differences in
      behavioral, cognitive, and affective characteristics of friendships. Greater
      conflict, poorer attachment quality, lesser ability to repair relationships,
      cognitive distortions, and poorer social-cognitive problem solving characterize
      delinquent friendships. There is little support for the superior quality of
      friendships of delinquents, as some had speculated. A failure to find differences
      between delinquents and nondelinquents in certain studies may be traced to use of
      single-index measures of qualitative aspects or variations in the sample studied,
      but this cannot be taken to mean there are no differences in the population from
      which the samples were drawn.

PMID- 9173781
TI  - Rural adolescent drinking behavior: three year follow-up in the New Hampshire
      substance abuse prevention study.
AB  - A three-year follow-up study of alcohol prevention among 4,406 children showed
      that neither a comprehensive school curriculum nor a community intervention was
      successful in preventing adolescent drinking. Predictor variables for drinking
      are examined and the importance of tolerance and encouragement of drinking by
      adult role models are noted.

PMID- 9173782
TI  - The relationship of dieting to weight in adolescents.
AB  - Using a sample of 1,269 high school students, black and white, male and female,
      this study compared the actual and preferred weights of dieters and nondieters
      and examined the relationship of increasing weight to preferred weight and the
      decision to diet. Seventy-two percent of the enrolled students in ten schools of
      a large metropolitan area participated in the study by completing a self
      administered questionnaire designed for the research. The mean age was 17.5 + or 
      0.6 years. To be identified as a dieter a student had to report having lost five
      or more pounds through dieting. Nearly half of the black and white males, two
      thirds of the black females, and three quarters of the white females met this
      criterion. Although mean heights of dieters and nondieters did not differ
      significantly in each race-sex group, dieters weighed at least 14 pounds more
      than nondieters. While dieters set higher preferred weights for themselves as
      their own weight increased, white male and female dieters preferred to weigh
      about 11 pounds less than black male and female dieters, respectively. The
      majority of dieters were not overweight; some were even underweight. This study
      documents the need for effective nutrition and exercise programs in the schools
      to help students accept and achieve reasonable weights.

PMID- 9173783
TI  - Adolescents in therapeutic communities.
AB  - This study was designed to compare the course of change of two groups of conduct
      disordered adolescents in two theoretically distinct residential treatment
      programs: a Therapeutic Community and a modified Token Economy. In all, 28
      clients were assessed on multiple measures at three points in the treatment
      process in a repeated measures design. Results of the study indicated that,
      despite an overall trend toward improvement in both groups, there was little
      significant difference between the rates of progress over time. Dropouts and
      nondropouts could be differentiated only by a small number of baseline scores and
      the amount of family contact during placement. While comparative studies in
      residential treatment have been lacking, it appears that a more promising
      approach would be to examine common features of different models. The results of
      this study support the need for qualitative research focusing on the interaction
      of client attributes and underlying components of treatment modalities.

PMID- 9173784
TI  - Knowledge and attitudes toward sexuality in adolescents and their association
      with the family and other factors.
AB  - Family structure and function and their association with knowledge and attitudes
      toward sexuality, contraception, and sexually transmitted diseases (STD) were
      studied in 918 students and 312 adolescents working in factories. Unmarried
      workers reported higher rates of sexual activity than did students (30.9% vs.
      21.8%, p = .04 for males; 12.9% vs. 6.0%, p = .005 for females). Among sexually
      active males, 33.3% of students and 30.7% of workers used contraception, compared
      with 27.5% of female students and 9.5% of female workers. Workers were from
      larger families than students, and the male and female workers had lower scores
      for knowledge on sexuality, contraception, and STD than did students. Multiple
      stepwise regression showed that age and schooling of the parents were associated
      with knowledge and attitudes in the students. In workers, the position of the
      child in the family was a negative regressor for attitudes and knowledge on
      sexuality in males, and for knowledge on contraception and STD in females. In
      regard to family function, the significant factors were compromise between the
      parents, positive affective response, communication within the family, problem
      solution, and control of behavior. It was concluded that female workers are at
      higher risk for unwanted pregnancies and STD. The factors associated with
      knowledge and attitudes were age, schooling of the parents, mother working out of
      home, position of the adolescent in the family, and the diverse aspects of family
      function.

PMID- 9173785
TI  - Adolescents' perceptions of the role of part-time work.
AB  - In contrast to the U.S., research on child employment in Britain has been
      relatively rare. This paper reports the findings from a study in which 1,220
      students, 12-16 years of age, in two comparable schools in England and Scotland
      completed questionnaires on their employment. While the nature and extent of
      employment were assessed by means of a questionnaire, a sub-sample of students (N
      = 56) participated in interviews to provide more detailed information on their
      experience of employment. Results indicate that Green (1990) may have been overly
      optimistic in arguing against the negative stereotype of the student worker, at
      least as far as the United Kingdom is concerned. Although students may be able to
      control whether they work, the interview data indicate that they have little
      control over their work environment and do not always view employment in a
      positive light.

PMID- 9173786
TI  - Education of Hispanic youth: a cultural lag.
AB  - This paper presents possible contributing factors to the educational lag and
      suggestions for strategies to improve attainment levels of Hispanic American
      youth.

PMID- 9173787
TI  - Understanding gender differences in adolescent sexuality.
AB  - More than 1,800 junior high school students were surveyed regarding sexual
      activity. It was found that females were less likely to have "ever had sex" but
      among nonvirgins there was little gender difference in frequency or recency.
      Items measuring sexual values indicated greater commitment to abstinence and less
      permissive sexual attitudes among females. Females also saw sexual activity as
      more detrimental to future goal attainment. They viewed parents as less
      approving, but were more likely to discuss sex and dating practices with them.
      They reported parents as having more rules and were more likely to believe that
      they were unfair, and that they had gone against the parents' rules. Females
      perceived less peer pressure for sex and more support for waiting. However, more
      males anticipated partner pressure for sex and believed they might "have sex"
      before marriage. Males and females reported no difference in the importance of
      parenthood, but more females saw teen parenthood as a problem. No gender
      differences were found for smoking or drinking. Significantly more males had
      experienced petting behavior. Females were more likely to believe that sexual
      urges can be controlled. It was concluded that understanding these differences
      can help in the design of sex education and social programs to address problems
      associated with adolescent sexuality.

PMID- 9173788
TI  - Recommended books for helping children deal with separation and divorce.
AB  - Books can be a useful tool for helping children deal with separation and divorce.
      Practitioners will find that books are available which offer realistic insight
      into the problems that children experience during family breakdown. These
      problems are noted, and annotated books on separation and divorce are presented.

PMID- 9173789
TI  - Abuse of dextromethorphan-based cough syrup as a substitute for licit and illicit
      drugs: a theoretical framework.
AB  - Drug abuse has been a national social problem in the United States for decades
      and is often complicated by the emergence of new types of abused drugs or new
      forms of abuse. The forms of abuse, particularly by young persons, include the
      search for substitutes for better-known substances. It is unclear, however, what
      factors determine the choice of drug or substance for experimentation,
      considering the wide range of choices. This paper attempts to delineate the
      factors which make Dextromethorphan-based cough syrup an attractive choice.

PMID- 9173790
TI  - Adolescent attitudes about rape.
AB  - A very significant problem in society is adolescent rape victimization and the
      growing number of adolescent perpetrators. This paper examines adolescent
      attitudes about rape in order to develop curricular materials. It is found that
      adolescents exhibit conservative attitudes about gender roles, general rape
      myths, and victim issues.

PMID- 9173791
TI  - Mother and adolescent knowledge of sexual development: the effects of gender,
      age, and sexual experience.
AB  - As part of a larger study on the impact of personal and family characteristics on
      adolescents' HIV risk and risk-reduction behavior, 90 adolescents and 73 mothers
      were asked to define in their own words seven terms related to sexual
      development: ejaculation, hormones, menstruation, ovulation, puberty, semen, and
      wet dreams. Mother and adolescent knowledge of sexual development terms and the
      effects of age and sexual experience on that knowledge were examined. Results
      suggest that the mothers were not able to adequately define the sexual
      development terms and thus may be ill-prepared to teach their children about sex
      or reinforce information they learn in school. Since adolescent knowledge did not
      significantly increase with age and sexual experience, the researchers suggest
      that continuing sex education about normal sexual development is needed.

PMID- 9173792
TI  - Adolescent depressed mood and parental unhappiness.
AB  - A set of self-report scales on depression, parental happiness, intimate
      relationships, social support, self-esteem, and risk-taking behavior were
      administered to 455 adolescents to determine the relationship between depression
      and these other variables. Adolescents with depressed mood were found to be less
      intimate with both parents, felt less social support, and had lower self-esteem
      than their peers. Adolescents who perceived their mother or father as unhappy
      also reported less intimacy with both parents and less social support.

PMID- 9173793
TI  - Family characteristics and adolescent substance use.
AB  - Using self-report questionnaire data from high school students (N = 253), the
      relation between adolescents' perceptions of family characteristics and
      adolescent substance use patterns were examined. Results indicated that
      adolescents' perception of maternal substance use, family hardiness, and age of
      the adolescent were significant predictors of adolescent substance use.
      Implications are presented.

PMID- 9173794
TI  - Dating-partner preferences among a group of inner-city African-American high
      school students.
AB  - The present study examines a set of characteristics that students may (or may
      not) value in a dating partner. A total of 80 inner-city high school students
      indicated how important they perceived certain qualities to be in a person they
      would like to date. Respondents were instructed to check the most appropriate
      category (very important, somewhat important, or not important) beside a list of
      12 phrases. In order to determine meaningful patterns, a rank-ordering of mean
      values and a rarely used multidimensional scaling model were employed to further
      understand this widely researched aspect of dating. The rank-ordering indicates
      relationships between the students and attributes, while the scaling model
      reflects patterns between the rated attributes only. The results are in contrast
      to the previous literature regarding dating-partner preferences among African
      American high school students.

PMID- 9173795
TI  - Treatment outcomes in an adolescent chemical dependency program.
AB  - A study was conducted of treatment outcomes for all admissions to an adolescent
      chemical dependency program over a ten-month period. Parents of patients were
      interviewed regarding their adolescents past behavioral characteristics, recovery
      oriented behaviors, drug use status, and adaptive behavior before and after
      discharge. Among the adolescents 26% had a history of special education
      placement; 12% had been diagnosed as being hyperactive; 57% had not used any
      drugs or alcohol since discharge from the treatment program, and this rate
      increased to 82% for use within the past month. Parents of adolescents who had
      used drugs or alcohol after treatment most often described it as either a brief
      relapse, or a series of relapses, or lower levels of use than prior to admission.
      According to parents estimates, 17% of adolescents were using more than 10% of
      the time since discharge. The effect of various pre-treatment and treatment
      factors on outcomes were investigated. Better treatment outcome was associated
      with older adolescents, greater participation in aftercare, and less time passage
      since discharge. Retrospective ratings by parents of adolescents regarding
      depressed, delinquent, and hyperactive behaviors showed that before admission all
      scales were in a "clinical range." After discharge all scales were in the normal
      range except for girls, who showed a borderline clinical elevation on depressed
      behaviors.

PMID- 9173796
TI  - Proceedings of the XIIIth International Symposium on Arterial Chemoreceptors.
      Santiago, Chile, March 25-29, 1996.

PMID- 9173797
TI  - Trauma and its sequelae in male prisoners: effects of confinement, overcrowding,
      and diminished services.
AB  - With explosive growth in prison populations, deteriorating conditions "inside,"
      and a large number of mentally disordered felons, correctional mental health
      programs are inundated with demands for services. Based on the author's first
      hand survey of state prisons, inmate responses to the harsh conditions are
      described and a link is suggested between childhood traumas of inmates and the
      traumas they experience in prison. Implications for correctional mental health
      services, as well as correctional policy in general, are offered.

PMID- 9173798
TI  - Self-injury in trauma survivors: 1. functions and meanings.
AB  - Self-injury is increasingly linked to traumatic childhood experiences, and is
      identified in this paper as a means by which some trauma survivors cope with post
      traumatic effects. It is proposed that self-injury serves a number of functions,
      organized here into four categories: re-enactment of the original trauma,
      expression of feelings and needs, reorganization of the self, and management of
      dissociative process.

PMID- 9173799
TI  - Self-injury in trauma survivors: 2. levels of clinical response.
AB  - Responding effectively to trauma survivors who engage in self-injury can be
      challenging, even for experienced therapists. This paper outlines therapeutic
      goals and appropriate clinical responses, including remaining present at and open
      to communication about disclosures of self-injury, helping clients to intervene
      in their own process of self-injury, and working with clients to resolve
      underlying issues. Alternatives to self-injury are discussed and cautions are
      offered about common therapeutic responses likely to be particularly unhelpful.

PMID- 9173800
TI  - The psychological tasks of marriage: part 2.
AB  - Findings from a pilot study of intimate relationships of 50 happily married
      couples show that many had troubled childhoods. Interactions of couples in
      creating and maintaining their good marriage throughout their lives are analyzed
      under the rubric of psychological tasks that these couples addressed
      successfully. Three of these tasks are focused on in this second of a two-part
      article.

PMID- 9173801
TI  - Impact of maternal alcoholism on separation of children from their mothers:
      findings from a sample of incarcerated women.
AB  - Patterns of maternal child co-residence among 25 alcoholic women incarcerated for
      drunk driving are examined. Two-thirds of these mothers reported significant
      periods of time, not due to incarceration, when minor children did not reside
      with them. Fewer than half of the placements were mandated by child-protective
      services. Having two or more children while actively alcoholic or residing with a
      substance abuser correlated strongly with separate residence.

PMID- 9173802
TI  - School performance and emotional problems in refugee children.
AB  - The relationship between school performance and emotional problems was assessed
      in a general population sample of refugee children from Southeast Asia and
      Central America. Results suggested that learning difficulties and levels of
      academic achievement were associated with emotional problems in both groups but
      that, despite comparable academic records, remedial measures were more often
      prescribed for Central American children.

PMID- 9173803
TI  - Sleep and anxieties in Brazilian children: the role of cultural and environmental
      factors in child sleep disturbance.
AB  - To test the contextual hypothesis of sleep disturbance, disadvantaged urban
      Brazilian children's self-reported fears were correlated with parental reports of
      children's sleep disturbance. Fears of death at the hands of "death squads,"
      environment-related worries and other fears reflecting Brazil's political,
      religious, and collective culture all correlated with sleep disturbance. Results
      are contrasted with findings of earlier studies on sleep and anxieties in samples
      of learning-disabled adolescents and victims of lightning.

PMID- 9173804
TI  - Patterns of grief reaction after pregnancy loss.
AB  - Analysis of three waves of Perinatal Grief Scale scores for 194 bereaved subjects
      over the course of two years revealed patterns of change different from those
      commonly noted in the literature. Less than half the sample matched the "normal"
      model; the rest exhibited non-normal patterns that did not fit the alternative
      psychological models. Demographic variables and pregnancy history, both before
      and after the loss, help explain some of the differences in direction of the
      grief response.

PMID- 9173805
TI  - The national lesbian family study: 1. interviews with prospective mothers.
AB  - This first report from a longitudinal study of 84 lesbian families, 70 of which
      include a co-mother as well as a birthmother whose child was conceived by donor
      insemination, presents interview data on parental relationships, social supports,
      pregnancy motives and preferences, stigmatization concerns, and coping
      strategies. Methodological limitations of studying this special population are
      noted, and plans for follow-up interviews over the course of 25 years are
      outlined.

PMID- 9173806
TI  - A statistics primer. Types of studies in the medical literature.

PMID- 9173807
TI  - [Computer program SAGE as a tool of standard assessment of patients on intensive
      care].

PMID- 9173808
TI  - [Assessing the probability of hypoxic complications in cardiosurgery patients
      using statistical simulation of hypoxia].
AB  - The program is based on measuring the parameters determining the relationships
      between oxygen, blood acid-base, and blood and urine water-electrolyte balance in
      150 patients after cardiopulmonary bypass surgery. Three degrees of homeostasis
      were distinguished: normal, hypoxic complications, and fatal hypoxic
      complications. The most informative laboratory tests reflecting the oxygen status
      and acid-base and water-electrolyte balance and indicating the presence and
      severity of hypoxic complications of homeostasis were selected. Graphic
      presentation of the probability scale predicting the hypoxic disorders helps more
      rapidly (than with the digital values) assess the severity of oxygen homeostasis
      disorders in patients. The PROGNOZ computer program may be used for the diagnosis
      and prediction of hypoxic disorders in intensive care units for cardiological and
      cardiosurgical patients.

PMID- 9173809
TI  - [Hypoxia and vascular-platelet hemostasis in patients with acute coronary
      insufficiency].
AB  - This study was aimed at investigation of a relationship between the parameters of
      hypoxia and platelet function and the antiaggregation activity of the vascular
      wall in patients with acute coronary failure. Seventy-four patients aged 31 to 78
      with unstable angina were examined. Prior to the treatment capillary and venous
      blood gases, activities of superoxide dismutase, catalase, levels of malonic
      dialdehyde and diene conjugates, and red cell peroxide resistance were measured.
      Platelet aggregation was studied before and after occlusion test. According to
      multifactorial statistical analysis, the type of gas exchange and lipid
      peroxidation processes has a strong impact on platelet function and
      antiaggregation activity of the vascular wall in patients with unstable angina.
      Hypoxia in these patients is associated with both pathogenic and compensatory
      changes in the vascular-platelet component of the homeostasis system, which
      should be borne in mind when carrying out antihypoxic therapy.

PMID- 9173810
TI  - [Anesthesiological and intensive care in war trauma].

PMID- 9173811
TI  - [A comparative study of the effectiveness of 5% human albumin and 10%
      hydroxyethyl starch (HAES-steril) for correcting hemodynamics and O2 transport in
      surgical interventions].
AB  - Forty patients subjected to cavitary operations were examined. A high risk of
      hemodynamic disorders necessitated invasive monitoring; with this aim in view a
      catheter was inserted for measuring arterial pressure and the Swan-Ganz catheter
      for measuring the pressure in the pulmonary artery, in which helped monitor the
      hemodynamics and oxygen transport in the course of hypervolemic hemodilution.
      Plasma substitutes (one of two) were selected at random. After catheterization of
      the left radial artery and insertion of the Swan-Ganz catheter in the pulmonary
      artery through the internal right jugular vein the patients were infused either
      5% human albumin or 10% hydroxyethyl starch in a dose of 125 ml every 5 min. The
      parameters of hemodynamics and oxygen transport were recorded after 500 ml of the
      solution was infused and the wedge pressure of 18 mm Hg attained. Both agents
      appreciably improved the mean arterial pressure, central nervous pressure, and
      wedge pressure. Cardiac index, left ventricular output, and stroke volume
      increased in both groups, and the pulmonary vascular resistance decreased. Both
      agents improved oxygen utilization and appreciably decreased hemoglobin level.
      The positive effect of hydroxyethyl starch on cardiac index, pulmonary vascular
      resistance, left ventricular output, and oxygen utilization was more expressed;
      moreover, a lesser dose of this drug was needed than of 5% human albumin
      (Behringwerke, Marburg, Germany). Loss of plasma caused by surgical intervention
      was better compensated for with synthetic colloid solutions, such as 10% HAES
      steril (Fresinium, Oberurzel, Germany), provided that plasma protein level was at
      least 3-4 g/dl. The effect of 10% HAES-steril as regards the increase of
      circulating blood volume is 145%. Due to the hyperoncotic direction of its action
      it has a positive impact on the hemodynamics and oxygen transport and is needed
      in lower doses than other colloid solutions.

PMID- 9173812
TI  - [Preoperative identification of ischemic heart disease in patients with surgical
      diseases of the abdominal cavity].
AB  - The authors present the results of preoperative identification of coronary
      diseases in patients with abdominal surgical diseases. Latent coronary diseases
      in surgical patients were detected by transesophageal electric stimulation (TEES)
      of the left atrium. Thirty-eight patients aged 46 to 82 were examined. Manifest
      symptoms of myocardial ischemia (changed ST segment, T wave inversion) were
      revealed in 47.3% patients, which is an evidence of the high resolving power of
      the method. Hence, noninvasive unsophisticated TEES technique is a reliable tool
      for identifying coronary diseases in surgical patients. The results of such
      examinations help adequately and purposefully prepare the patients to surgery and
      select the method of total anesthesia involving the minimal risk.

PMID- 9173813
TI  - [Respiratory aid to patients with severe forms of suppurative meningitis].
AB  - The severity of acute respiratory failure (ARF) in patients with purulent
      meningitis (PM) depends on the severity of consciousness disorders. ARF is most
      expressed in comatose patients, whereas in PM involving no consciousness
      disorders there were no changes of the gaseous composition of the blood or acid
      base status. After forced ventilation of the lungs is started, gaseous
      composition of the blood normalizes. Timely active respiratory care decreased by
      half the mortality in this patient population, this indicating that such patients
      are to be treated in intensive care wards for timely correction of disordered
      vital functions.

PMID- 9173815
TI  - [Fiber optics oximetry of blood in the upper bulb of the internal jugular vein in
      heart surgery].
AB  - The authors assess the potentialities of a new method; fiber optic oxyhemometry
      of the blood flowing from the brain (at the level of the upper bulb of the
      internal jugular vein) during heart surgery. They demonstrate a sufficiently high
      accuracy of the method. Using it during cardiosurgical operations under
      artificial circulation, they found it highly informative and sensitive to even
      suddenly emerging and short-term changes in the ratio of oxygen
      delivery/consumption by the brain.

PMID- 9173814
TI  - [Main principles of rapid diagnosis and intensive care in emergency states: their
      realization in expert systems].
AB  - A retrospective analysis of 543 case histories over 1980-1990 in the town of
      Yekaterinburg and analysis of published data permitted the authors to single out
      the signs characterizing the most frequent syndromes requiring urgent intensive
      care. By either diagnostic value, these signs are distributed into main,
      accessory, and ruling out. An expert system has been created, making use of the
      productive-Freimont's approach to representing information on the basis of
      blurred multiplicities and ambiguous logics. The diagnosis was made by stages:
      first the main signs were analyzed, determining the severity of patient's status,
      then (after first aid was rendered) accessory and ruling out signs, which help
      make the diagnosis more precise. The system was tried in 231 patients, 102 of
      these with acute respiratory failure, 63 with acute hemodynamic insufficiency,
      and 66 with acute cerebral insufficiency. Primary diagnosis of the underlying
      syndrome was correct in 87-89% of cases, of the concomitant syndrome in 92-97%.
      Repeated evaluations (in 1-3 and 24 h) taking account of the time course of the
      symptoms and of the results of unsophisticated instrumental examinations
      increased the share of correct diagnoses to 92-96%.

PMID- 9173816
TI  - [Dynamics of lipid peroxidation in correction of acquired heart diseases under
      conditions of hypothermia without perfusion].

PMID- 9173817
TI  - [Cessation of prolonged artificial ventilation of the lungs and transition to
      spontaneous respiration of surgical patients].

PMID- 9173818
TI  - [State of lipid peroxidation in patients with ischemic heart disease during
      aortocoronary bypass surgery using epidural anesthesia].
AB  - Effects of epidural anesthesia (EA) on free-radical lipid oxidation and the
      antioxidant system were studied in coronary patients during aortocoronary bypass
      operations and in the immediate postoperative period in comparison with patients
      operated on under common anesthesia (without EA). Thirty-six patients (men) aged
      42.4 +/- 1.4 years were examined. EA as a component of total anesthesia in
      aortocoronary bypass surgery was conducive to a lesser activation of free-radical
      lipid oxidation. After surgery EA sooner normalized free-radical oxidation and
      the antioxidant system, which was observed at the end of the operation and during
      the first 24 h after it. During artificial circulation EA did not appreciably
      affect the degree of activation of free-radical oxidation.

PMID- 9173819
TI  - [Characteristics of amino acid metabolism in patients with severe sepsis and
      septic shock].
AB  - The development of the multiorgan dysfunction syndrome, directly determining the
      severity of the septic process, is characterized by not only inverse ratio of the
      energy and plastic material, but by metabolic changes which are still unclear and
      cannot yet be explained. Our purpose was to detect some features of amino acid
      metabolism in patients with grave sepsis and septic shock. The concentrations of
      plasma free amino acids were measured on days 1, 3, and 5 in 37 patients with
      grave sepsis and septic shock. The diagnosis of grave sepsis, septic shock, and
      organ dysfunction was made proceeding from the criteria defined by R. Bone. The
      study revealed reliably increased (p < 0.05) levels of arginine, proline,
      alanine, and the arginine-ornithine index reflecting the direction of arginine
      transformation in patients with septic shock and grave organ dysfunction (for at
      least 3 systems). This may be explained by active degradation of endogenous
      proteins of skeletal muscles, which is characteristic of septic hypermetabolism.
      Strong correlations were revealed between arginine level and the APACHE-II score
      (r = 0.57), proline and the same score (r = 0.51), mean arterial pressure and the
      arginine-ornithine index (r = -0.72), APACHE-II score and the arginine-ornithine
      index (r = 0.79), arterial lactate and the arginine-ornithine index (r = 0.64).
      Hence, amino acid metabolism apparently mediates the effects of septic cascade
      mediators on the following cell.

PMID- 9173820
TI  - [Feedback monitoring systems in anesthesiology].

PMID- 9173821
TI  - [Choice of the method of anesthesia in long and traumatic surgery].

PMID- 9173822
TI  - [Effects of induction propofol mono-narcosis on the central and cerebral
      hemodynamics].
AB  - Changes in the central hemodynamics were followed up by echocardiography and the
      linear velocity of the bloodflow by transcranial dopplerography in 15 patients
      with ASA classes I-II during induction bolus anesthesia with propofol in a dose
      2.7 mg/kg without opioids. The diastolic and mean arterial pressure decreased by
      12.3 and 15.4 %, respectively, the rate of cardiac contractions by 7.8%, cardiac
      index by 13.4%, and the resistive index on the radial and middle cerebral
      arteries by 13.4 and 10.2%, respectively, after administration of the above dose
      of propofol. The reaction to intubation of the trachea was the minimal,
      consisting in an increase of the mean and systolic arterial pressure by 22.2 and
      22.7%, respectively, and of diastolic by 16.1%. The rest parameters were as
      initially. The linear velocity of the bloodflow in the middle cerebral artery did
      not reliably change. Hence, the central hemodynamic parameters are stable on
      condition that the deficit in the central bloodflow during induction anesthesia
      with propofol in a dose of 2.7 mg/kg is compensated for, adequate protection from
      intubation stress is provided, and autoregulation of the cerebral bloodflow is
      preserved.

PMID- 9173823
TI  - [The state of the hypophyseal-adrenal system during surgical correction of heart
      diseases under conditions of different anesthesia and in distant periods after
      surgery].
AB  - Blood plasma levels of 11-HOCS were measured in 278 patients with heart diseases
      operated on under different anesthesia at various stages of surgical correction
      of the diseases and during the immediate postoperative period. Blood plasma ACTH
      levels were measured in 137 patients operated on under deep hypothermal
      protection and hypothermal perfusion. The most manifest hormonal response was
      observed during surgery under normothermia, whereas under conditions of
      hypothermal perfusion the reaction to intervention was the minimal. A total of
      141 patients were examined in remote periods after surgery. Blood plasma 11-HOCS
      levels were normal in patients with good and satisfactory results of surgical
      treatment and increased for decreased in those with unsatisfactory results.

PMID- 9173824
TI  - [Epidural electric neurostimulation in the protocols of anesthesia in plastic and
      reconstructive surgery].

PMID- 9173825
TI  - [Prognostication of complications in surgery of lung cancer].
AB  - Examinations of 286 men subjected to pneumonectomy demonstrated the possibility
      of predicting the immediate results of intervention on the basis of a
      comprehensive analysis of blood rheology, lipid peroxidation, cell (T lymphocyte,
      leukocyte, and reticulocyte counts) and gaseous composition of the blood (paO2,
      paCO2, and pHmet) and the characteristics of the structural and optic reaction of
      the blood serum to low-intensive laser exposure in vitro. This algorithm for
      predicting complications based on the minimal set of informative criteria proved
      to be correct in 75% of patients before surgery and 82.2% of patients on day 1
      postoperation.

PMID- 9173826
TI  - [Readaptation after total intravenous anesthesia in one-day surgery].
AB  - The authors analyze the stages of readaptation and recovery of clear
      consciousness in the immediate postoperative period in 200 patients administered
      one of the four variants of intravenous anesthesia in a one-day surgical
      hospital. The purpose of this work was to optimize the anesthetic care and the
      readaptation period. The stages of readaptation were assessed by
      psychophysiological testing. This process coursed most smoothly after propofol
      phentanyl and hypnomidate-phentanyl anesthesia. Readaptation after sombrevin
      phentanyl coursed reliably slower. The longest recovery was observed after
      calipsol-diazepam anesthesia, despite drug stimulation. This type of narcosis is
      irrational for one-day surgery, for it requires prolonged postoperative
      monitoring and thus makes the hospital stay longer.

PMID- 9173827
TI  - [Use of the CRITIKON Cerebral Redox for cerebral oximetry].

PMID- 9173828
TI  - [Analysis of respiratory complications during artificial ventilation of the lungs
      in patients with organophosphorus compound poisoning].
AB  - The authors analyze the respiratory complications in patients with acute
      respiratory failure (ARF) developing as a result of poisoning with
      organophosphorous (OPC). Twenty-two percent of 470 patients had to be maintained
      on forced ventilation because of ARF. The indications for forced ventilation of
      the lungs are as follows: paralysis of respiratory muscles, 90% drop of vital
      capacity of the lungs, and disorders of the gaseous composition of the blood
      (PaCO2 over 56 +/- 3 mm Hg and PaO2 below 67 +/- 5 mm Hg). The incidence of
      respiratory complications among patients on forced ventilation was as high as
      92%, which is due to the pathogenesis of the chemical disease developing after
      OPC poisoning. The complications are the most incident among men aged 30 to 60.
      The respiratory distress syndrome of adults ranks first among the respiratory
      complications. It was diagnosed in 70.6% of dead subjects in 34.4% of
      convalescents. This syndrome is one main cause of high mortality, particularly so
      in subjects dying in three or more days of intensive care. The duration of forced
      ventilation of the lungs does not depend on the time when the patient was
      transferred on ventilation or on the poison. Analysis of mortality indicates that
      it is lower among patients administered forced ventilation at the prehospital
      stage.

PMID- 9173829
TI  - [Use of hemodialysis in intensive care of organophosphorus insecticide
      poisoning].
AB  - A total of 163 hemoperfusions carried out in order to remove poison in patients
      with acute poisoning with organophosphorous insecticides (OPI) showed that this
      treatment modality effectively removes OPI from te organism. In patients with the
      most severe forms of acute poisoning hemoperfusion may be effectively combined
      with hemadsorption and peritoneal dialysis. This variant of detoxication ensures
      a good clinical effect and a stable decrease of the toxic agent in the blood. The
      proposed method of blood stabilization with sodium citrate in the extracorporeal
      contour provides a reliable extracorporeal stabilization of the blood and does
      not deteriorate the efficacy of hemoperfusion.

PMID- 9173830
TI  - [Effects of amitriptyline on the contractile function of the myocardium. Dobutrex
      in the role of a positive inotropic agent].
AB  - Study of the effect of a tricyclic antidepressant amitriptyline on an isolated
      papillary muscle of the rat left ventricle showed a decrease of the contractility
      due to depression of the potential of action and the slow calcium channels, as
      well as decreased rate and prolongation of contraction caused by impairment of
      calcium reabsorption from the sarcoplasma. Injection of dobutrex after
      amitriptyline has a positive inotropic effect by completely removing the
      disorders in the time parameters of contraction.

PMID- 9173831
TI  - [Variants of the use of hemosorption in patients with acute clofelin poisoning].
AB  - Indications to hemadsorption in patients with grave poisonings with clofelin have
      been defined. Two variants of hemadsorption for such patients have been developed
      and tried: hemadsorption in parallel with transesophageal
      electrocardiostimulation and that with blood stabilization with sodium citrate in
      the extracorporeal contour. Hemadsorption brought about a good clinical effect,
      normalized hemo- and cardiodynamics, removed depression of the sinus node
      function and the conduction tract of the heart. Sodium citrate stabilization of
      the blood did not exert a negative impact on the cardiovascular function and
      decreased the incidence of hemorrhagic complications.

PMID- 9173832
TI  - [Disorders of central hemodynamics and phase structure of left ventricle systole
      in patients with veratrine poisoning].
AB  - Central hemodynamics, phase structure of left ventricular systole, and
      circulating blood volume were studied in 56 patients with acute poisoning with
      veratrine. Two main variants of hemodynamic disorders were distinguished.
      Exposure of up to 3-4 hours led to bradycardia with heart rate of up to 47/min
      but no appreciable hemo- or cardiodynamic disorders. A longer exposure resulted
      in a decrease of the circulating blood volume, development of the phase syndrome
      of myocardial hypodynamia with a drop of stroke volume and cardiac output and
      development of hypotonia. These results indicate the necessity of a
      differentiated approach to the treatment of circulatory disorders in patients
      poisoned with veratrine.

PMID- 9173833
TI  - [Artificial ventilation of the lungs in respiratory failure caused by lesions of
      the peripheral neuron].
AB  - A case with 155-day artificial ventilation of the lungs (AVL) in a patient with
      the poliencephalomyelitic form of tick-borne encephalitis is described. AVL was
      conducted through tracheostoma by the Puritan-Bennett 720ae device in the CMU
      mode for 26 days, then in the SIMU + PS accessory mode for 7 days, and in the
      CPAP + PS mode for 155 days. Despite the recovery of spontaneous respiration,
      vital capacity of the lungs did not normalize (1.1 liter) and the involvement at
      the level of the spine and the nuclei of the craniocerebral nerves was not
      corrected. The compensation was evidently due to training the diaphragm and the
      respiratory muscles and joining the accessory muscles.

PMID- 9173834
TI  - [Advantages, hazards and prospects of using autologous blood in aortocoronary
      bypass surgery].

PMID- 9173835
TI  - [Aspects of using ozone in medicine].

PMID- 9173836
TI  - [Present problems with infant vaccination].

PMID- 9173837
TI  - [Meningococcal infection: should we vaccinate?].

PMID- 9173838
TI  - [The evaluation of autopsy in the pediatric intensive unit].
AB  - OBJECTIVE: Because of concerns about the declining autopsy rate, an attempt was
      made to evaluate the contributions from the postmortem examination in children.
      PATIENTS AND METHODS: We carried out a retrospective comparison analysis between
      clinical and pathological diagnosis of 56 consecutive autopsies performed on
      children who died in the PICU during the period 1983-1995. RESULTS: The autopsy
      rate was 60%. Autopsy provided valuable clinical information in 50% of the cases.
      There were major diagnostic errors in three patients (5%), that if detected
      before death would probably have improved survival. Another 14 cases (25%) showed
      missed clinical diagnoses related to the basic illness and the cause of death,
      whose premortem diagnosis would not have prolonged survival. There were no
      diagnostic discrepancies in 28 cases (50%). The most unexpected findings revealed
      by the autopsies were iatrogenics (10 cases), metabolic diseases (4 cases),
      congenital immunodeficiency syndromes (4 cases) and pulmonary opportunistic
      infections (3 cases). Eight of these diseases were genetic. An age < 12 months or
      and ICU stay < 24 hours were not predicting factors of a higher incidence of
      major diagnostic errors. CONCLUSIONS: The value of the autopsy as quality
      assurance and to detect iatrogenics and occult genetic diseases is
      unquestionable. New strategies have to be designed to increase the rate of
      autopsies.

PMID- 9173839
TI  - [Polycaries in temporal dentition: a continuing problem].
AB  - OBJECTIVE: The purpose of this study was to evaluate the different factors
      related to the presence of multiple caries (polycaries) in children less than 6
      years old. PATIENTS AND METHODS: A study was carried out on 88 patients treated
      consecutively. The following factors were evaluated: age, sex, socioeconomic
      level, caries indices ("co" index), presence of protective factors,
      predisposition, dietary habits, and treatment performed. RESULTS: Polycaries was
      not associated with the sex of the patient, but it was associated with
      unfavorable socioeconomic level (60%), the absence of preventative methods
      against the caries (100%), lack of oral hygiene (97.7%) and dietary errors (78%).
      The "co" index obtained was 9.54. Ninety percent of the patients had to be
      treated under general anesthesia. CONCLUSIONS: Polycaries in the temporary teeth
      is an important pathology, avoidable with early preventative methods and hygiene
      and educating the parent about oral health.

PMID- 9173840
TI  - [Meningococcal infection: changes in serogroups and penicillin resistance].
AB  - OBJECTIVE: There has been an increasing number of strains of meningococcus with
      reduced susceptibility to penicillin in Spain during the past few years. The
      serogroup distribution has also changed during this period. The objective of this
      study was to estimate the incidence of different N. meningitidis serogroups, the
      penicillin susceptibility and the clinical and laboratory data from the patients
      with meningococcal disease in our hospital. PATIENTS AND METHODS: A retrospective
      study of the patients admitted to the hospital during a 4 year period (1993-1996)
      with bacteriological data of meningococcal sepsis/meningitis was performed.
      Serogroup and penicillin minimum inhibitory concentration (MIC) were determined.
      Analysis of the clinical data from the patients with disease due to serogroups B
      or C was also performed. RESULTS: The incidence of serogroups C and B was 47% and
      51.6%, respectively. There were 5 cases of decreased susceptivility to penicillin
      (MIC 0 0.25 microgram/ml). There were no clinical differences between the two
      groups of patients. CONCLUSIONS: There was a progressive increase in the
      incidence of serogroup C, while the incidence of serogroup B remained stable, as
      did the cases of meningococci with reduced susceptibility to penicillin. Although
      this study did not suggest a modification in the initial treatment, every strain
      of meningococci must be studied to show penicillin MIC to avoid treatment
      failure.

PMID- 9173841
TI  - [Outbreak of meningitis caused by echovirus type 30].
AB  - OBJECTIVES: In the cold months of 1994-1995, we detected in our hospital an
      epidemic outbreak of acute enteroviral meningitis caused by echovirus type 30
      (Echo 30). Until now, these outbreaks of viral epidemics had not been detected in
      Spain. PATIENTS AND METHODS: We reviewed retrospectively 46 clinical histories of
      patients who were admitted to our hospital between September 1994 and January
      1995 with the diagnosis of acute lymphocytic meningitis, analyzing the clinical
      outbreak, epidemiological and laboratory characteristics, and how the outbreak
      spread. RESULTS: Regarding the patients, there was a prevalence in males, with an
      average age of 6 years and a range of 2 to 13 years of age. The most constant
      symptom was severe frontal headache, with signs of meningitis in only 50% of the
      cases. In the CSF, we found a predominance of PMN in the differential cell count
      in 63% of the cases, with the time of evolution before spinal puncture less than
      24 hours in the majority of the patients. Viral cultures were performed on CSF,
      stool and throat scrapings in 16 patients with Echo 30 being isolated in 15
      cases, which suggests 32.6% of the total cases. CONCLUSIONS: We detected in our
      environment an epidemic outbreak of viral meningitis caused by an agent not found
      previously in Spain, which presented epidemiological, clinical and laboratory
      characteristics similar to those reported in the literature. Its appearance
      during the cold months contrasts to what normally occurs.

PMID- 9173842
TI  - [Tuberculosis infection prevalence in children younger than 7 years of age in
      Cantabria. What is the recommended periodicity for the tuberculin tes?].
AB  - OBJECTIVE: Because of the disparity between the recommendations regarding age and
      frequency for the realization of tuberculin testing during childhood, a study of
      tuberculous infection prevalence according to age was made in order to establish
      at which ages tuberculin testing would be recommendable and to determine if there
      is a difference in prevalence between vaccinated and non-vaccinated children.
      PATIENTS AND METHODS: A study was carried out by performing annual tuberculin
      tests (4,454) using the Mantoux technique on 1,710 boys and girls between 1 and 6
      years of age. Of these, 796 (46.54%) had been vaccinated with BCG at birth.
      Children on which a diagnostic tuberculin test had been carried out were excluded
      from the study. Indurations larger or equal to 10mm were considered positive, in
      vaccinated as well as in non-vaccinated children, until the publication and
      adoption of the criterion recommended by the National Concensus for Tuberculosis
      Control in Spain in 1992. Thereafter, indurations larger or equal to 5 mm in non
      vaccinated children and larger than 14 mm in vaccinates children were considered
      positive. RESULTS: The prevalence of tuberculosis infection was 0.49%, 1.87%, and
      6,66% at one, 4 and 6 years of age, respectively, in non-vaccinated children and
      0.31%, 2.25% and 8,69% at the same ages in vaccinated children was compared and
      no statistically significant difference was found. CONCLUSIONS: We recommend the
      realization of tuberculin tests at one and 4 years of age and show that, in our
      medium, vaccinated children have a tuberculous infection prevalence during early
      childhood similar to their non-vaccinated counterparts.

PMID- 9173843
TI  - [Distribution of lipidic values in teenagers that smoke].
AB  - OBJECTIVE: To determine the lipidic profiles in a population of teenagers and
      determine their relationship with smoking. PATIENTS AND METHODS: We have studied
      910 teenagers, between 14 and 17 years of age. Information regarding smoking was
      obtained with a questionnaire. Serum levels of cholesterol, HDL, LDL,
      triglycerides, apoprotein A and apoprotein B were measured by enzymatic methods.
      RESULTS: Total cholesterol of non-smokers is higher than in smokers. Even if we
      divide the population studied by gender, the difference remain. Nevertheless,
      smokers' mean HDL level is lower, especially in boys. The LDL/HDL index is
      slightly higher in smokers than in non-smokers. However, if we separate boys and
      girls, we found some differences. Boys that smoke have higher cholesterol/HDL and
      LDL/HDL than non-smoking boys. Adjusting lipidic values by body mass, age and
      triglyceride serum levels, the relationship between smoking and lower
      cholesterol, HDL and apoprotein A and higher serum triglyceride levels remains in
      boys.

PMID- 9173844
TI  - [Epidemiological study of nocturnal enuresis: analysis of associated factors].
AB  - OBJECTIVE: The purpose of this study was to analyze the different pathogenic
      factors in a large population of children. PATIENTS AND METHODS: A transverse
      epidemiological study was performed. Schoolchildren in the province of Leon
      between 6 and 10 years of age were studied during the 1991-1992 academic year. A
      randomly chosen sample of 2,165 children was used. The study was carried out by
      means of an anonymous survey given to the children's parents by the school.
      RESULTS: In addition to family antecedents of enuresis, the main associated
      factors were the mother's cultural status, with enuresis more frequent if the
      status was low, and the child's birth order. CONCLUSIONS: This study shows that
      certain family conditions favor the development of nocturnal enuresis.

PMID- 9173845
TI  - [Application of neonatal ECMO in Spain. The foundations and the roof].

PMID- 9173846
TI  - [Extracorporeal membrane oxygenation (ECMO). I. Is it really needed in Spain?].
AB  - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory
      support technique used to treat newborns with severe respiratory insufficiency.
      ECMO has not been used yet in newborns in Spain, with its necessity being
      question. The aim of this study was to evaluate the need for ECMO for respiratory
      or cardiac cases in our neonatal population, as well as to study the predictive
      capacity of several respiratory indices. PATIENTS AND METHODS: A retrospective
      observational study was carried out. Data from 2,133 newborns admitted during a
      48 month period was reviewed. Babies were considered ECMO candidates if they died
      of respiratory failure or after surgery for a cardiac defect and if they had no
      ECMO exclusion criteria. The capacity of several respiratory indices to predict
      mortality was analyzed. RESULTS: We considered 16 babies who died to be ECMO
      candidates, 6 with respiratory failure (1/3,028 live births) and 10 with cardiac
      defects 3 of them inborn (1/6,057). The total ECMO need was 1/2019 live births.
      None of the oxygenation indices studied accurately predicted the 80% mortality
      rate. CONCLUSIONS: In Spain, it is necessary to start several neonatal ECMO
      programs since some 200 newborn infants with severe respiratory failure or
      cardiac defects could benefit from such a program annually.

PMID- 9173847
TI  - [Extracorporeal membrane oxygenation (ECMO). II. The development of an
      experimental model in newborn lambs].
AB  - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a technique used for
      cardiorespiratory support in the treatment of newborns with severe respiratory
      insufficiency. ECMO has not been used yet in newborns in Spain. The aim of this
      work was to develop an experimental veno-arterial ECMO model in newborn lambs for
      training the NICU medical and nursing staff before the clinical application of
      this technique. MATERIAL AND METHODS: Six newborn lambs were anesthetized,
      traqueotomized and connected to a neonatal ventilator. The right jugular vein and
      left carotid artery were cannulated and the catheters were located in the right
      atrium and aortic arch, respectively. A venous-arterial ECMO was performed during
      three hours, with an experimental ECMO circuit developed by us. Arterial pH and
      blood gases, systemic and airway pressures, heart rate, and rectal temperature
      were monitored. RESULTS: The experimental ECMO circuit developed by use had a
      very low cost, but was capable of maintaining adequate gas exchange, acid-base
      balance and a normal rectal temperature. CONCLUSIONS: The development of an
      experimental ECMO model in newborn lambs may allow the establishment of an
      initial training program and to maintain the expertise of the NICU staff of a
      perinatal center planning to start an ECMO program.

PMID- 9173848
TI  - [Early onset of neonatal sepsis due to Streptococcus agalactiae: study of ten
      years (1985-1994) and the utility of intrapartum prophylaxis].
AB  - OBJECTIVES: The objectives of this study were to determine the characteristics of
      early onset neonatal sepsis (EONS) due to group B streptococci (GBS) in our
      population and to evaluate the efficacy of a prevention program in our hospital
      during a 4 year period. MATERIAL AND METHODS: We revised all cases of EONS due to
      GBS between 1985 and 1994 and studied pregnant women colonized by GBS and their
      infants between 1991 and 1994. RESULTS: In ten years, we diagnosed 45 cases of
      EONS due to GBS, 30 born in our hospital and 15 born in other hospitals. Sixty
      two percent of the patients presented some risk factor (gestation < 37 weeks,
      rupture of membranes > 18 hours or intrapartum fever > or = 37.8 degrees C.
      Between 1991 and 1994, 93% of pregnant women colonized by GBS received antibiotic
      prophylaxis, 14.7% of these women had some risk factor for infection. Two infants
      from mothers colonized had EONS due to GBS. One mother did not receive antibiotic
      prophylaxis and the other presented intrapartum fever. In another 5 cases
      observed during this period, the vaginal culture of the mother was negative for
      GBS. The incidence of EONS due to GBS during these 4 years was 0.82 cases per
      1,000 live births. CONCLUSION: We consider it necessary to use antibiotic
      prophylaxis in all pregnant carriers of GBS, as well as the administration of
      antibiotics to pregnant women with a rupture of membranes < 34 weeks of gestation
      and the practice of an intrapartum culture for the detection of GBS in pregnant
      women without previous cultures and premature rupture of the membranes.

PMID- 9173849
TI  - [Effectiveness of medical treatment of endocarditis due to Candida in premature
      newborns].

PMID- 9173851
TI  - [Neonatal gastric opening].

PMID- 9173850
TI  - [Deep vein thrombosis in a child with chicken pox as a clinical manifestation of
      streptococcal sepsis].

PMID- 9173852
TI  - [Generalized acute exanthematous pustulosis: two case reports].

PMID- 9173854
TI  - [Komoto syndrome: a case review].

PMID- 9173853
TI  - [Akinesia sequence/fetal hypokinesia (Pena-Shokeir syndrome): four case reports].

PMID- 9173855
TI  - [Recurrent meningitis caused by Escherichia coli].

PMID- 9173856
TI  - [Obstructive renal insufficiency due to Candida. Fluconazole as a valid
      alternative to classical therapy].

PMID- 9173857
TI  - [Von-Voss-Cherstvoy syndrome (DK-Focomelia): description of the first case in
      Spain and a literature review].

PMID- 9173858
TI  - [Casual radiological finding of a isquiopubian lithical image].

PMID- 9173859
TI  - [The introduction to molecular biology and its application go pediatrics (4):
      study of mutations in DNA amplified by PCR].

PMID- 9173860
TI  - [Keratitis caused by Shigella sonnei: a case report. Letter].

PMID- 9173861
TI  - [On the administration of fluor to infants].

PMID- 9173862
TI  - [The sleeping position and deformities caused by compression: an alert for
      outpatient pediatricians. Letter].

PMID- 9173863
TI  - [Meningitis caused by Neisseria meningitidis of serogroup C. Letter].

PMID- 9173864
TI  - Correction: duplicate publication.

PMID- 9173865
TI  - [Abduction of the toes and the fan sign (Babinski, 1903)].

PMID- 9173867
TI  - DNA polymerase beta: analysis of the contributions of tyrosine-271 and asparagine
      279 to substrate specificity and fidelity of DNA replication by pre-steady-state
      kinetics.
AB  - DNA polymerase beta (pol beta) from rat brain, overexpressed in Escherichia coli,
      was used as a model to study the factors responsible for substrate specificity
      [kpol, Kd(app) and kpol/Kd(app)] and fidelity during DNA synthesis. The roles of
      two active-site residues, Asn-279 and Tyr-271, were examined by construction of
      N279A, N279Q, Y271A, Y271F and Y271S mutants followed by structural analyses by
      NMR and CD and functional analyses by pre-steady-state kinetics. The results are
      summarized as follows. (i) None of the two-dimensional NMR spectra of the mutants
      was significantly perturbed relative to that for wild-type pol beta, suggesting
      that Tyr-271 and Asn-279 are not important for the global structure of the
      protein. (ii) CD analyses of guanidinium hydrochloride-induced denaturation
      showed that all mutants behaved similarly to the wild type in the free energy of
      denaturation, suggesting that Tyr-271 and Asn-279 are not critical for the
      conformational stability of pol beta. (iii) The Kd(app) for the correct dNTP was
      lower than that for the incorrect dNTP by a factor of 10-30 in the case of wild
      type pol beta. Upon mutation to give N279A and N279Q, the Kd(app) for the correct
      dNTP increased by a factor of 15-25. As a consequence, the Kd(app) values for the
      correct and incorrect nucleotides were similar for N279A and N279Q, suggesting
      that the main function of the side chain of Asn-279 is in discrimination between
      the binding of correct and incorrect dNTPs. (iv) In the case of the Y271A mutant,
      the fidelity and the catalytic efficiency kpol/Kd(app) were little perturbed
      relative to the wild type. However, both the kpol and Kd(app) values for dNTP
      were 4-8 times lower in the case of the Y271A mutant than the corresponding
      values for wild-type pol beta. Since the chemical step may not be rate-limiting
      for wild-type pol beta, the effect on kpol could be quite significant if it is
      caused by a perturbation in the chemical step. (v) Pol beta displayed the
      greatest specificity towards the G:C base pair, which is incorporated during base
      excision repair of G:U and G:T mispairs. This specificity was slightly enhanced
      for the Y271F mutant.

PMID- 9173869
TI  - The flux control coefficient of carnitine palmitoyltransferase I on palmitate
      beta-oxidation in rat hepatocyte cultures.
AB  - Two important factors that determine the flux of hepatic beta-oxidation of long
      chain fatty acids are the availability of fatty acid and the activity of
      carnitine palmitoyltransferase I (CPT I). Using Metabolic Control Analysis, the
      flux control coefficient of CPT I in rat hepatocyte monolayers was determined by
      titration with 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir),
      which is converted to Etomoxir-CoA, an irreversible inhibitor of CPT I. We
      measured CPT I activity and flux through beta-oxidation at 0.2 mM and 1.0 mM
      palmitate to simulate substrate concentrations in fed and fasted states. Rates of
      beta-oxidation were 4.5-fold higher at 1. 0 mM palmitate compared with 0.2 mM
      palmitate. Flux control coefficients of CPT I, estimated by two independent
      methods, were similar: 0.67 and 0.79 for 0.2 mM palmitate, and 0.68 and 0.77 for
      1 mM palmitate. It is concluded that the regulatory potential of CPT I is similar
      at low and high physiological concentrations of palmitate.

PMID- 9173868
TI  - Identification of ErbB3-stimulated genes using modified representational
      difference analysis.
AB  - The epidermal growth factor receptor (EGFR) family of tyrosine kinases is
      involved in the growth of normal and tumour cells. The specific contribution of
      each of the four family members to these processes remains unclear. In the
      present study we have used a PCR-based subtractive approach to identify
      differences in messages induced in response to activation of ErbB3 and EGFR. The
      approach described is a modification of the representational difference analysis
      technique adapted for analysis of cDNA, which we have modified to permit
      identification of differential gene expression using as little as 20 microg of
      total RNA as the starting material. The mRNA obtained from EGF-stimulated NIH-3T3
      cells expressing chimaeric EGFR-ErbB3 receptors provided the tester amplicons
      (small PCR-amplified fragments) which were subtracted against driver amplicons
      derived from unstimulated NIH-3T3 cells expressing the EGFR-ErbB3 chimaera or EGF
      stimulated NIH-3T3 cells overexpressing the EGFR. A total of 22 different clones
      were isolated, 90% of which showed increased expression in the tester amplicons.
      Six of these, corresponding to known DNA sequences, were selected for further
      Northern blot analysis against total RNA prepared from the starting cell lines.
      Of these, the gene encoding the protein dlk (or a closely related protein, Pref
      1) was identified as being regulated by ErbB3 but not by the EGFR. Other genes
      appeared to be elevated by both ErbB3 and EGFR, including those encoding c-jun,
      Ret finger protein (RFP), neuroleukin and amyloid protein precursor. One gene
      product, TIS11, was identified as being regulated by EGFR but not by ErbB3.

PMID- 9173866
TI  - Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in
      cell signalling.
AB  - The intracellular concentration of free unbound acyl-CoA esters is tightly
      controlled by feedback inhibition of the acyl-CoA synthetase and is buffered by
      specific acyl-CoA binding proteins. Excessive increases in the concentration are
      expected to be prevented by conversion into acylcarnitines or by hydrolysis by
      acyl-CoA hydrolases. Under normal physiological conditions the free cytosolic
      concentration of acyl-CoA esters will be in the low nanomolar range, and it is
      unlikely to exceed 200 nM under the most extreme conditions. The fact that acetyl
      CoA carboxylase is active during fatty acid synthesis (Ki for acyl-CoA is 5 nM)
      indicates strongly that the free cytosolic acyl-CoA concentration is below 5 nM
      under these conditions. Only a limited number of the reported experiments on the
      effects of acyl-CoA on cellular functions and enzymes have been carried out at
      low physiological concentrations in the presence of the appropriate acyl-CoA
      buffering binding proteins. Re-evaluation of many of the reported effects is
      therefore urgently required. However, the observations that the ryanodine
      senstitive Ca2+-release channel is regulated by long-chain acyl-CoA esters in the
      presence of a molar excess of acyl-CoA binding protein and that acetyl-CoA
      carboxylase, the AMP kinase kinase and the Escherichia coli transcription factor
      FadR are affected by low nanomolar concentrations of acyl-CoA indicate that long
      chain acyl-CoA esters can act as regulatory molecules in vivo. This view is
      further supported by the observation that fatty acids do not repress expression
      of acetyl-CoA carboxylase or Delta9-desaturase in yeast deficient in acyl-CoA
      synthetase.

PMID- 9173871
TI  - Cloning, sequencing and characterization of the 5'-flanking region of the human
      collagenase-3 gene.
AB  - Collagenase-3 (matrix metalloprotease-13) is a recently discovered human
      collagenase produced in normal articular cartilage chondrocytes and thought to be
      involved in the pathological process of osteoarthritis. We have sequenced and
      characterized 1.6 kb of the human collagenase-3 gene 5'-flanking region. The
      transcription start site was located 22 bp upstream from the ATG start codon.
      Sequence analysis of the 5'-flanking region revealed the presence of the
      consensus recognition sites for the TATA and CCAAT DNA-binding proteins,
      activator protein-1 and E26 transformation specific/polyoma virus enhancer, as
      well as three core motifs of hormone response elements. Transient transfection
      assays demonstrated that a small fragment of 133 bp, containing the activator
      protein-1 and E26 transformation specific/polyoma virus enhancer sites promoted
      transcription in normal and osteoarthritic human chondrocytes with significantly
      higher activity than the original 1.6 kb fragment. Nucleotide sequence comparison
      of the promoter region of human collagenase-3 revealed a stronger similarity to
      the mouse collagenase-1 promoter than to the human collagenase-1 promoter.

PMID- 9173870
TI  - Slow kinetics of inositol 1,4,5-trisphosphate-induced Ca2+ release: is the
      release 'quantal' or 'non-quantal'?
AB  - Inositol 1,4,5-trisphosphate (InsP3)-induced Ca2+ release from intracellular
      stores is generally assumed to be a 'quantal' process because low InsP3
      concentrations mobilize less Ca2+ than high concentrations and a submaximal
      concentration does not release all the InsP3-mobilizable Ca2+. However, some
      recent reports questioned the generally accepted view that a low dose of InsP3 is
      unable to empty the whole store. We have now challenged the stores of
      permeabilized A7r5 cells in InsP3 for much longer periods than previously
      reported, to assess directly whether the slow phase of the release would empty
      the whole store (a non-quantal response) or only a fraction of it (a quantal
      response). Addition of a maximal [InsP3] at the end of a prolonged (92 min)
      stimulation with a submaximal [InsP3] resulted in additional Ca2+ release.
      Experiments in which the stores were challenged with different submaximal InsP3
      concentrations for long time periods revealed that a lower [InsP3] never released
      the same amount of Ca2+ as a higher [InsP3]. This quantal pattern of Ca2+ release
      occurred both at 25 degrees C and at 4 degrees C. There was a time-dependent
      increase in the fraction of Ca2+ recruited by the lower compared with the higher
      [InsP3]. This recruitment of Ca2+ persisted if the [InsP3] was decreased, but was
      largely prevented by palmitoyl-CoA, a potent blocker of the luminal Ca2+
      translocation between individual store units. ATP, in the presence of InsP3,
      released Ca2+ under conditions permitting the recruitment of no additional InsP3
      receptors, indicating that an all-or-none emptying of a fraction of the stores
      cannot be the only mechanism responsible for quantal Ca2+ release in A7r5 cells.
      We conclude that some of the previously published evidence for a non-quantal Ca2+
      release pattern should be reinterpreted.

PMID- 9173872
TI  - Delineation of the arginine- and tetrahydrobiopterin-binding sites of neuronal
      nitric oxide synthase.
AB  - Nitric oxide synthase (EC 1.14.13.39) catalyses the conversion of arginine, NADPH
      and oxygen to nitric oxide and citrulline, using haem, (6R)-5,6,7,8-tetrahydro-l
      biopterin (tetrahydrobiopterin), calmodulin, FAD and FMN as cofactors. The enzyme
      consists of a central calmodulin-binding sequence flanked on the N-terminal side
      by a haem-binding region that contains the arginine and tetrahydrobiopterin sites
      and on the C-terminal side by a region homologous with NADPH:cytochrome P-450
      reductase. By using domain boundaries defined by limited proteolysis of full
      length enzyme, recombinant haem-binding regions of rat brain neuronal nitric
      oxide synthase were expressed and purified. Two proteins were made in high yield:
      one, corresponding to residues 221-724, contained bound haem and
      tetrahydrobiopterin and was able to bind Nomega-nitro-l-arginine (nitroarginine)
      or arginine; the other, containing residues 350-724, contained bound haem but was
      unable to bind tetrahydrobiopterin, nitroarginine or arginine. These results
      showed that rat brain neuronal nitric oxide synthase contains a critical
      determinant for arginine/tetrahydrobiopterin binding between residues 221 and
      350. Limited proteolysis with chymotrypsin of the former protein resulted in a
      new species with an N-terminal residue 275 that retained the ability to bind
      nitroarginine, further defining the critical region for arginine binding as being
      between 275 and 350. Comparison of the sequences of nitric oxide synthase and the
      tetrahydrobiopterin-requiring amino acid hydroxylases revealed a similarity in
      the region between residues 470 and 600, suggesting that this might represent the
      core region of the pterin-binding site. The stoichiometries of binding of
      substrate and cofactors to the recombinant domains were not more than 0.5 mol/mol
      of monomer, suggesting that there might be a single high-affinity site per dimer.

PMID- 9173873
TI  - Cysteine-200 of human inducible nitric oxide synthase is essential for
      dimerization of haem domains and for binding of haem, nitroarginine and
      tetrahydrobiopterin.
AB  - Nitric oxide synthase (EC 1.14.13.39) is a homodimer. Limited proteolysis has
      previously shown that it consists of two major domains. The C-terminal or
      reductase domain binds FMN, FAD and NADPH. The N-terminal or oxygenase domain is
      known to bind arginine, (6R)-5,6,7,8-tetrahydro-l-biopterin (tetrahydrobiopterin)
      and haem. The exact residues of the inducible nitric oxide synthase (iNOS)
      protein involved in binding to these molecules have yet to be identified,
      although the haem moiety is known to be co-ordinated through a cysteine thiolate
      ligand. We have expressed two forms of the haem-binding domain of human iNOS
      (residues 1-504 and 59-504) in Escherichia coli as glutathione S-transferase
      (GST) fusion proteins. The iNOS 1-504 and 59-504 fusion proteins bound similar
      amounts of haem, Nomega-nitro-l-arginine (nitroarginine) and tetrahydrobiopterin,
      showing that the first 58 residues are not required for binding these factors.
      Using site-directed mutagenesis we have mutated Cys-200, Cys-217, Cys-228, Cys
      290, Cys-384 and Cys-457 to alanine residues within the iNOS 59-504 haem-binding
      domain. Mutation of Cys-200 resulted in a complete loss of haem, nitroarginine
      and tetrahydrobiopterin binding. Mutants of Cys-217, Cys-228, Cys-290, Cys-384 or
      Cys-457 showed no effect on the haem content of the fusion protein, no effect on
      the reduced CO spectral peak (444 nm) and were able to bind nitroarginine and
      tetrahydrobiopterin at levels equivalent to the wild-type fusion protein. After
      removal of the GST polypeptide, the wild-type iNOS 59-504 domain was dimeric,
      whereas the C200A mutant form was monomeric. When the mutated domains were
      incorporated into a reconstructed full-length iNOS protein expressed in Xenopus
      oocytes, only the Cys-200 mutant showed a loss of catalytic activity: all the
      other mutant iNOS proteins showed near wild-type enzymic activity. From this
      systematic approach we conclude that although Cys-217, Cys-228, Cys-290, Cys-384
      and Cys-457 are conserved in all three NOS isoforms they are not essential for
      cofactor or substrate binding or for enzymic activity of iNOS, and that Cys-200
      provides the proximal thiolate ligand for haem binding in human iNOS.

PMID- 9173874
TI  - Glutathione S-transferase Yc cDNA from Syrian hamster kidney.
AB  - A cDNA encoding alpha-class glutathione S-transferase Yc (GSTYc) has been
      isolated from a Syrian hamster kidney library, and its nucleotide sequence (968
      bp) has been determined. Analysis of the deduced amino acid sequence revealed a
      high level of identity between Syrian hamster GSTYc, rat GST Yc1 and Yc2 and
      mouse GSTYc. Northern-blot experiments demonstrated that Syrian hamster GSTYc
      expression is tissue-specific. A GSTYc mRNA of approx. 1 kb is expressed in
      liver, kidney, vas deferens and epididymis. Expression of the GSTYc transcript
      was not detected in testis or uterus.

PMID- 9173875
TI  - The nuclear autoantigen La/SS-associated antigen B: one gene, three functional
      mRNAs.
AB  - Transcription of the gene encoding for the nuclear autoantigen La resulted in
      three mRNA forms. A promoter switching combined with an alternative splicing
      pathway replaced exon 1 with either exon 1' or exon 1'. The exon 1' donor splice
      site was located 4 nts downstream of the exon 1' donor splice site. All three La
      mRNA forms were expressed in all the tissues analysed including peripheral blood
      lymphocytes, liver, fetal spleen, cultured primary endothelial cells, and mouse
      LTA cell lines permanently transfected with the human La gene. Both the exons 1'
      and 1' had unusual structures. They contained GC-rich regions and an oligo(U)
      tail of 23 uridine residues. Moreover, they encoded for three open reading frames
      upstream of the La protein reading frame. In spite of this unusual structure,
      when exon 1' or exon 1' La mRNAs were expressed in transfected mouse LTA cells,
      both La mRNAs were translated to nuclear La protein, indicating that all La mRNA
      forms are functional mRNAs.

PMID- 9173876
TI  - Characterization of bovine endothelial nitric oxide synthase as a homodimer with
      down-regulated uncoupled NADPH oxidase activity: tetrahydrobiopterin binding
      kinetics and role of haem in dimerization.
AB  - The fatty-acylation-deficient bovine endothelial NO synthase (eNOS) mutant (Gly-2
      to Ala-2, G2AeNOS) was purified from a baculovirus overexpression system. The
      purified protein was soluble and highly active (0.2-0.7 micromol of l-citrulline.
      mg-1.min-1), contained 0. 77+/-0.01 equivalent of haem per subunit, showed a
      Soret maximum at 396 nm, and exhibited only minor uncoupling of NADPH oxidation
      in the absence of l-arginine or tetrahydrobiopterin. Radioligand binding studies
      revealed KD values of 147+/-24.1 nM and 52+/-9.2 nM for specific binding of
      tetrahydrobiopterin in the absence and presence of 0.1 mM l-arginine
      respectively. The positive co-operative effect of l-arginine was due to a
      pronounced decrease in the rate of tetrahydrobiopterin dissociation (from 1.6+/
      0.5 to 0. 3+/-0.1 min-1). Low-temperature SDS gel electrophoresis showed that
      approx. 80% of the protein migrated as haem-containing dimer after preincubation
      with l-arginine and tetrahydrobiopterin. Gel-filtration chromatography yielded
      one peak with a Stokes radius of 6.8+/-0.04 nm, corresponding to a hydrodynamic
      volume of 1. 32x10(-24) m3, whereas haem-deficient preparations (approx. 0.3
      equivalent per subunit) contained an additional protein species with a
      hydrodynamic radius of 5.1+/-0.2 nm and a corresponding volume of 0.55x10(-24)
      m3, suggesting that haem availability regulates eNOS dimerization.

PMID- 9173877
TI  - Design of kallidin-releasing tissue kallikrein inhibitors based on the
      specificities of the enzyme's binding subsites.
AB  - The tissue kallikrein inhibitors reported in the present work were derived by
      selectively replacing residues in Nalpha-substituted arginine- or phenylalanine
      pNA (where pNA is p-nitroanilide), and in peptide substrates for these enzymes.
      Phenylacetyl-Arg-pNA was found to be an efficient inhibitor of human tissue
      kallikrein (Ki 0.4 microM) and was neither a substrate nor an inhibitor of plasma
      kallikrein. The peptide inhibitors having phenylalanine as the P1 residue behaved
      as specific inhibitors for kallidin-releasing tissue kallikreins, while plasma
      kallikrein showed high affinity for inhibitors containing (p-nitro)phenylalanine
      at the same position. The Ki value of the most potent inhibitor developed, Abz
      Phe-Arg-Arg-Pro-Arg-EDDnp [where Abz is o-aminobenzoyl and EDDnp is N-(2,4
      dinitrophenyl)-ethylenediamine], was 0.08 microM for human tissue kallikrein.
      Progress curve analyses of the inhibition of human tissue kallikrein by benzoyl
      Arg-pNA and phenylacetyl-Phe-Ser-Arg-EDDnp indicated a single-step mechanism for
      reversible formation of the enzyme-inhibitor complex.

PMID- 9173878
TI  - Overt and latent activities of diacylglycerol acytransferase in rat liver
      microsomes: possible roles in very-low-density lipoprotein triacylglycerol
      secretion.
AB  - The possibility that triacylglycerol (TAG) synthesis occurs on both aspects of
      the endoplasmic-reticular membrane during the process of incorporation of TAG
      into secreted very-low-density lipoprotein (VLDL) [Zammit (1996) Biochem. J. 314,
      1-14] was investigated by measuring the latency of diacylglycerol acyltransferase
      (DGAT) in microsomal fractions obtained from rat liver homogenates.
      Permeabilization of microsomes with taurocholate resulted in the doubling of the
      activity, indicating that DGAT activities of approximately equal magnitude occur
      on either aspect of the microsomal membrane. The taurocholate concentrations
      required for exposure of the latent activity of DGAT were identical with those
      that resulted in the exposure of marker enzymes for the lumen of the endoplasmic
      reticulum. Fractionation of the microsomes into smooth and rough populations
      indicated that the distribution of overt and latent DGAT activities was the same
      throughout. The possibility that taurocholate effects may result from non
      specific activation of the overt enzyme was excluded by employing the channel
      forming peptide alamethicin to effect permeabilization, and by varying the mode
      of delivery of diacylglycerol substrate to the microsomal membranes.
      Permeabilization using alamethicin gave a slightly higher latent/overt ratio for
      DGAT. The possible roles of overt and latent DGAT activities in the synthesis and
      secretion of TAG by the liver are discussed.

PMID- 9173879
TI  - Cell-surface ADP-ribosylation of fibroblast growth factor-2 by an arginine
      specific ADP-ribosyltransferase.
AB  - Basic fibroblast growth factor (FGF-2) appeared to be ADP-ribosylated on the
      surface of adult bovine aortic arch endothelial and human hepatoma cells. Further
      characterization of this reaction with cells expressing an arginine-specific,
      glycosylphosphatidylinositol-anchored, mono-ADP-ribosyltransferase demonstrated
      that FGF-2 is ADP-ribosylated on arginine. Incubation of transformed cells with
      FGF-2 and [adenylate-32P]nicotinamide-adenine dinucleotide (NAD) resulted in the
      rapid incorporation of [32P]ADP-ribose into FGF-2 in a time- and concentration
      dependent manner, with labelling averaging 3 mol of ADP-ribose/mol of FGF-2.
      Excess ADP-ribose had no effect on these reactions, whereas excess NAD inhibited
      the ADP-ribosylation of FGF-2, consistent with an enzymic rather than a non
      enzymic ADP-ribosylation reaction. Heparin also inhibited the ADP-ribosylation
      reaction, whereas a neutralizing polyclonal anti-peptide antibody had no effect.
      Furthermore, the addition of putative receptor binding domain peptide analogues
      of FGF-2 reduced the maximal ADP-ribosylation of FGF-2. These results identify
      the cell-surface ADP-ribosylation of FGF-2 as a potentially ubiquitous event.

PMID- 9173881
TI  - Response of microtubules to the addition of colchicine and tubulin-colchicine:
      evaluation of models for the interaction of drugs with microtubules.
AB  - The effects of free drug and tubulin-drug complexes on steady-state GTP/GDP
      associated microtubules and on equilibrium guanosine 5'[beta,gamma
      imido]triphosphate-associated microtubules are compared. The addition of
      colchicine or the tubulin-colchicine complex (TuCol) to steady-state microtubules
      induces microtubule disassembly. Only limited disassembly of equilibrium
      microtubules is observed under similar conditions. Addition of colchicine or the
      bifunctional colchicine analogue 2-methoxy-5-(2'3',4'-trimethoxyphenyl)tropone to
      preassembled steady-state or equilibrium microtubules does induce disassembly,
      but establishment of the new steady state or equilibrium is very slow. These
      observations are related to the fact that TuCol readily adds to the microtubule
      end, but is only incorporated into the lattice with difficulty. As a result,
      microtubule growth is effectively inhibited and the critical concentration is
      significantly increased. Nevertheless, drug-induced disassembly can be extremely
      slow, because the frequency of addition reactions increases as the concentration
      of soluble dimers increases. The efficiency of incorporation of TuCol decreases
      as it concentration increases. The work further confirms the existence of
      colchicine-binding sites with low affinity (association constant KMT
      approximately 3 x 10(2) M-1) along the microtubule lattice. This value suggests
      that part of the colchicine-binding site on tubulin remains available in the
      polymer. The interaction of colchicine with these sites has no appreciable effect
      on microtubule dynamics. These observations are reproduced and rationalized by
      the model described elsewhere [Vandecandelaere, Martin, Bayley and Schilstra
      (1994) Biochemistry 33, 2792-2801], and the possibility that there are co
      operative effects in the inhibition is considered.

PMID- 9173880
TI  - Evidence for multiple forms of biotin holocarboxylase synthetase in pea (Pisum
      sativum) and in Arabidopsis thaliana: subcellular fractionation studies and
      isolation of a cDNA clone.
AB  - The intracellular compartmentation of biotin holocarboxylase synthetase has been
      investigated in pea (Pisum sativum) leaves, by isolation of organelles and
      fractionation of protoplasts. Enzyme activity was mainly located in cytosol
      (approx. 90% of total cellular activity). Significant activity was also
      identified in the soluble phase of both mitochondria and chloroplasts. Two enzyme
      forms were separated by anion-exchange chromatography. The major form was found
      to be specific for the cytosol compartment, whereas the minor form was present in
      mitochondria as well as in chloroplasts. We also report the isolation and DNA
      sequence of a cDNA encoding an Arabidopsis thaliana biotin holocarboxylase
      synthetase. This cDNA was isolated by functional complementation of a conditional
      lethal Escherichia coli birA (biotin ligase gene, which regulates biotin
      synthesis) mutant. This indicated that the recombinant plant protein was able to
      biotinylate specifically an essential apoprotein substrate in the bacterial host,
      that is a subunit of acetyl-CoA carboxylase called biotin carboxyl carrier
      protein. The full-length nucleotide sequence (1534 bp) encodes a protein of 367
      amino acid residues with a molecular mass of 41172 Da and shows specific regions
      of similarity to other biotin holocarboxylase synthetase genes as isolated from
      bacteria and yeast, and with cDNA species from human. A sequence downstream of
      the first translation initiation site encodes a putative peptide structurally
      similar to organelle-targeting pre-sequences, suggesting a mitochondrial or
      chloroplastic localization for this isoform.

PMID- 9173882
TI  - An apparent association between glycosylphosphatidylinositol-anchored proteins
      and a sphingolipid in Tetrahymena mimbres.
AB  - Sphingolipids are thought to stabilize glycosylphosphatidylinositol (GPI)
      anchored protein-rich membrane domains of yeast and polarized higher animal cells
      during the processing and targeting of these proteins to the plasma membrane. A
      widely used criterion for identifying the stable sphingolipid- and GPI-anchored
      protein-enriched membrane domains is the resistance of these lipid-modified
      proteins to solubilization by the detergent Triton X-100 (TX-100) at low
      temperature. Surprisingly, there have been no reports of sphingolipid/GPI
      anchored protein association in protozoans, despite the fact that these cells
      contain considerably higher levels of GPI-anchored proteins than does any other
      organism. We report here the presence in Tetrahymena mimbres of a significant
      pool of GPI-anchored proteins which resisted extraction by 1% TX-100 at 4 degrees
      C but not at 37 degrees C. Of the total cellular complement of GPI-anchored
      proteins, which together accounted for more than 2% of whole-cell protein and
      were especially enriched in surface membranes, 10% of the major 63kDa component
      (gpi63) and 23% of a somewhat less abundant component (gpi23) were insoluble in
      TX-100 at 4 degrees C. A substantial proportion of the cell's only abundant
      sphingolipid, ceramideaminoethylphosphonate (CAEP), was also insoluble in 1% TX
      100 at 4 degrees C. Radiolabelling studies involving [3H]leucine incorporation
      into proteins and [3H]palmitic acid incorporation into lipids revealed that the
      TX-100-resistant gpi63, gpi23 and CAEP molecules were all metabolically distinct
      from their TX-100-soluble counterparts in other compartments of the cell. The
      presence of detergent-resistant sphingolipid/GPI-anchored protein domains in non
      polarized ciliate and trypanosomatid cells was probably obscured in previous
      studies by the profusion of accompanying detergent-soluble molecules.

PMID- 9173883
TI  - Study of the role of the highly conserved residues Arg9 and Arg64 in the
      catalytic function of human N-acetyltransferases NAT1 and NAT2 by site-directed
      mutagenesis.
AB  - The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 are responsible for the
      biotransformation of many arylamine and hydroxylamine xenobiotics. It has been
      proposed that NATs may act through a cysteine-linked acetyl-enzyme intermediate
      in a general base catalysis involving a highly conserved arginine residue such as
      Arg64. To investigate this possibility, we used site-directed mutagenesis and
      expression of recombinant human NAT1 and NAT2 in Escherichia coli. Sequence
      comparison with NATs from other species indicated that Arg9 and Arg64 are the
      only invariant basic residues. Either mutation of the presumed catalytic Cys68
      residue or the simultaneous mutation of Arg9 and Arg64 to Ala produced proteins
      with undetectable enzyme activity. NAT1 or NAT2 singly substituted at Arg9 or
      Arg64 with Ala, Met, Gln or Lys exhibited unaltered Km values for arylamine
      acceptor substrates, but a marked loss of activity and stability. Finally, double
      replacement of Arg9/Arg64 with lysine in NAT1 altered the Km for arylamine
      substrates (decreased by 8-14-fold) and for acetyl-CoA (elevated 5-fold), and
      modified the pH-dependence of activity. Thus, through their positively charged
      side chains, Arg9 and Arg64 seem to contribute to the conformational stability of
      NAT1 and NAT2 rather than acting as general base catalysts. Our results also
      support a mechanism in which Arg9 and Arg64 are involved in substrate binding and
      transition-state stabilization of NAT1.

PMID- 9173884
TI  - Expression and mutagenesis of the catalytic domain of cGMP-inhibited
      phosphodiesterase (PDE3) cloned from human platelets.
AB  - We have used reverse transcriptase PCR, platelet mRNA and degenerate primers
      based on platelet peptide sequences, to amplify a fragment of platelet cGMP
      inhibited phosphodiesterase (cGI-PDE; PDE3). Sequence analysis of this clone
      established that both the platelet and the cardiac forms of PDE3 were derived
      from the same gene (PDE3A). A RT-PCR product representing the C-terminal half of
      platelet PDE3 cDNA and corresponding to amino acid residues 560-1141 of the
      cardiac enzyme, was cloned and expressed in Escherichia coli cGI-PDEDelta1.
      Further deletion mutants were constructed by removing either an additional 100
      amino acids from the N-terminus (cGI-PDEDelta2) or the 44-amino-acid insert
      characteristic of the PDE3 family, from the catalytic domain (cGI
      PDEDelta1Deltai). In addition, site-directed mutagenesis was performed to explore
      the function of the 44-amino-acid insert. All mutants were evaluated for their
      ability to hydrolyse cAMP and cGMP, their ability to be photolabelled by
      [32P]cGMP and for the effects of PDE3 inhibitors. The Km values for hydrolysis of
      cAMP and cGMP by immunoprecipitates of cGI-PDEDelta1 (182+/-12 nM and 153+/-12 nM
      respectively) and cGI-PDEDelta2 (131+/-17 nM and 99+/-1 nM respectively) were
      significantly lower than those for immunoprecipitates of intact platelet PDE3
      (398+/-50 nM and 252+/-16 nM respectively). Moreover, N-terminal truncations of
      platelet enzyme increased the ratio of Vmax for cGMP/Vmax for cAMP from 0.16+/
      0.01 in intact platelet enzyme, to 0.37+/-0.05 in cGI-PDEDelta1 and to 0.49+/
      0.04 in cGI-PDEDelta2. Thus deletion of the N-terminus enhanced hydrolysis of
      cGMP relative to cAMP, suggesting that N-terminal sequences may exert selective
      effects on enzyme activity. Removal of the 44-amino-acid insert generated a
      mutant with a catalytic domain closely resembling those of other PDE gene
      families but despite a limited ability to be photolabelled by [32P]cGMP, no
      cyclic nucleotide hydrolytic activities of the mutant were detectable. Mutation
      of amino acid residues in putative beta-turns at the beginning and end of the 44
      amino-acid insert to alanine residues markedly reduced the ability of the enzyme
      to hydrolyse cyclic nucleotides. The PDE3 inhibitor, lixazinone, retained the
      ability to inhibit cAMP hydrolysis and [32P]cGMP binding by the N-terminal
      deletion mutants and the site-directed mutants, suggesting that PDE3 inhibitors
      may interact exclusively with the catalytic domain of the enzyme.

PMID- 9173885
TI  - Transcriptional activation of the minimal human Proalpha1(I) collagen promoter:
      obligatory requirement for Sp1.
AB  - A construct containing human Proalpha1(I) collagen gene promoter/enhancer-driven
      chloramphenicol acetyltransferase (CAT), pCOL-KT, failed to be expressed
      significantly in Sp1-deficient Schneider Drosophila line 2 (SL2) cells. However,
      CAT expression was induced 200-fold in SL2 cells co-transfected with pCOL-KT and
      pPACSp1, an Sp1-expression vector driven by the Drosophila actin 5C promoter.
      Elimination of the four potential Sp1-binding sites from pCOL-KT (pCOL-KTDeltaI),
      by removal of the first intron, did not abrogate Sp1-mediated induction of CAT.
      Even more significantly, a minimal Proalpha1(I) collagen promoter (-100 to +117
      bp), containing a TATA box (-28 to -25 bp) and one putative Sp1-binding site (-87
      to -82 bp), elicited strong Sp1-induced transactivation. Furthermore, mutation of
      the Sp1 motif in the minimal Proalpha1(I) collagen promoter-CAT construct
      abolished Sp1-induced expression of the reporter gene. Purified Sp1 protein bound
      specifically to DNA fragments of the Proalpha1(I) minimal promoter encompassing
      the putative Sp1-binding site; Sp1 binding could be competed out by a double
      stranded oligonucleotide containing the wild-type Sp1 sequence, while an
      oligonucleotide containing a mutated Sp1 site failed to compete. Based on these
      results, we postulate that Sp1 plays an obligatory role in the transcriptional
      activation of the human Proalpha1(I) collagen gene. Additionally, we propose that
      a bona fide Sp1 motif, located most proximal to the TATA box, is necessary and
      sufficient for Sp1-mediated activation of the minimal Proalpha1(I) collagen
      promoter.

PMID- 9173886
TI  - Sequence-selective binding to DNA of bis(amidinophenoxy)alkanes related to
      propamidine and pentamidine.
AB  - The DNA sequences targeted by a complete homologous series of aromatic diamidines
      have been determined at single-nucleotide resolution via protection from cutting
      by the endonucleases DNase I, DNase II and micrococcal nuclease. Propamidine,
      pentamidine and to a lesser extent hexamidine bind selectively to nucleotide
      sequences composed of at least four consecutive A-T base pairs. In contrast, the
      binding to DNA of butamidine, heptamidine, octamidine and nonamidine is poorly
      sequence-selective. Sequences composed of only three consecutive A-T base pairs
      do not afford a potential binding site for propamidine or the longer homologues,
      and none of the drugs tolerate the presence of a G-C base pair within the binding
      site. Experiments with DNA molecules containing inosine in place of guanosine and
      2,6-diaminopurine in place of adenine reveal that the lack of binding of
      propamidine to GC-containing sites is attributable to an obstructive effect of
      the exocyclic 2-amino group of guanosine. The present data support the view that
      the local conformation of the double helix (in particular the width of the minor
      groove) plays a dominant role in the binding reaction and that the capacity of
      diamidines to recognize AT-rich sequences selectively varies considerably
      depending on the length of the alkyl chain. The evidence indicates that binding
      to AT-tracts in DNA must play a role in the biological activity of these
      diamidines, but there is no simple correlation between binding and
      pharmacological efficacy.

PMID- 9173887
TI  - Actin is cleaved during constitutive apoptosis.
AB  - Proteases play an important role in the programme of cell death by apoptosis but
      little is known of the substrates cleaved, particularly in constitutive models of
      this type of cell death. Neutrophils spontaneously undergo apoptosis in culture
      without requiring external stimuli. During this process we found biochemical and
      immunochemical evidence for the cleavage of membrane-associated actin, a
      component of the cytoskeleton that links polymerized actin to the plasma
      membrane. Cleavage occurred at a single site at the N-terminus, between residues
      Val43-Met44, a site devoid of a consensus motif for cleavage by cysteine
      proteases of the interleukin-1beta-converting enzyme (ICE)-family. Whereas actin
      cleavage and nuclear/cell surface markers of apoptosis were co-ordinately
      diminished by zVAD-fmk, an inhibitor of the ICE-like family of proteases, only
      acetyl-leucyl-leucylnormethional, an inhibitor of calpains, was capable of
      completely inhibiting actin cleavage. Our results suggest that actin is not a
      direct substrate for the ICE-like family of proteases. By disabling the
      cytoskeleton, actin cleavage may be an important component in the capacity of
      apoptosis to reduce the injurious potential of neutrophils.

PMID- 9173888
TI  - N-terminal binding domain of Galpha subunits: involvement of amino acids 11-14 of
      Galphao in membrane attachment.
AB  - Heterotrimeric guanine nucleotide binding proteins (G-proteins) transmit signals
      from membrane receptors to a variety of intracellular effectors. G-proteins
      reversibly associate with components of the signal transduction system, yet
      remain membrane attached throughout the cycle of activation. The Galpha subunits
      remain attached to the plasma membrane through a combination of factors that are
      only partially defined. We now demonstrate that amino acids within the N-terminal
      domain of Galpha subunits are involved in membrane binding. We used in vitro
      translation, a technique widely utilized to characterize functional aspects of G
      proteins, and interactions with donor-acceptor membranes to demonstrate that
      amino acids 11-14 of Galphao contribute to membrane binding. The membrane binding
      of Galphao lacking amino acids 11-14 (D[11-14]) was significantly reduced at all
      membrane concentrations in comparison with wild-type Galphao. Several other N
      terminal mutants of Galphao were characterized as controls, and these results
      indicate that differences in myristoylation, palmitoylation and betagamma
      interactions do not account for the reduced membrane binding of D[11-14].
      Furthermore, when membrane attachment of Galphao and mutants was characterized in
      transiently transfected 35S-labelled and [3H]myristate-labelled COS cells, amino
      acids 11-14 contributed to membrane binding. These studies reveal that membrane
      binding of Galpha subunits occurs by a combination of factors that include lipids
      and amino acid sequences. These regions may provide novel sites for interaction
      with membrane components and allow additional modulation of signal transduction.

PMID- 9173889
TI  - The transcription of the human fructose-bisphosphate aldolase C gene is activated
      by nerve-growth-factor-induced B factor in human neuroblastoma cells.
AB  - A DNA region located at around -200 bp in the 5' flanking region (region D) of
      the human brain-type fructose-bisphosphate aldolase (aldolase C) gene has been
      analysed. We show by transient transfection assay and electrophoretic-mobility
      shift assay (EMSA) that the binding of transcriptional activators to region D is
      much more efficient (80% versus 30%) in human neuroblastoma cells (SKNBE) than in
      the non-neuronal cell line A1251, which contains low levels of aldolase C mRNA.
      The sequence of region D, CAAGGTCA, is very similar to the AAAGGTCA motif present
      in the mouse steroid 21-hydroxylase gene; the latter motif binds nerve-growth
      factor-induced B factor (NGFI-B), which is a member of the
      thyroid/steroid/retinoid nuclear receptor gene family. Competition experiments in
      EMSA and antibody-directed supershift experiments showed that NGFI-B is involved
      in the binding to region D of the human aldolase C gene. Furthermore, the
      regulation of the aldolase C gene (which is the second known target of NGFI-B)
      expression during development parallels that of NGFI-B.

PMID- 9173891
TI  - Stability of a thermophilic TIM-barrel enzyme: indole-3-glycerol phosphate
      synthase from the thermophilic archaeon Sulfolobus solfataricus.
AB  - The stability and activity of indole-3-glycerol phosphate synthase from
      Sulfolobus solfataricus were studied as a function of pH and temperature. In this
      paper we focus on three points: (1) the long-term stability of the protein to
      irreversible denaturation at high temperature; (2) the short-term stability of
      the protein to reversible temperature-driven unfolding; and (3) the dependence of
      its activity on temperature. Results can be summarized as follows: (a) the same
      first-order kinetic constant (0.020+/-0.003 min-1) was determined at different pH
      values (6.5, 8.0 and 9.5) from long-term stability experiments at 80 degrees C;
      (b) short-term stability experiments revealed different behaviour in two
      different pH ranges (6.5-8.0, 8.5-9.5), suggesting that the melting temperature
      is higher at alkaline than at neutral pH; (c) the dependence of activity on
      temperature was investigated at pH 7.0 and 9.0, and a discontinuity was observed
      in the Arrhenius plot of kcat values at pH 9.0. We also investigated the
      stability in the presence of guanidinium chloride at 20 degrees C either at pH
      7.0 or at pH 9.0, and we present data that indicate that the unfolding mechanism
      closely approaches a two-state model at pH 7.0 and a more complex mechanism at pH
      9.0. Satisfactory fitting of the equilibrium unfolding transition obtained by
      fluorescence measurements at pH 9.0 required a model that involves a stable
      intermediate in addition to the native and unfolded forms. At 20 degrees C the
      folded conformation is more stable than the unfolded conformation by (14. 7+/
      1.2) kJ/mol at pH 7.0 and by (25.5+/-1.8) kJ/mol at pH 9.0.

PMID- 9173890
TI  - 5-Hydroxytryptamine-induced calcium-channel gating in rainbow trout (Oncorhynchus
      mykiss) peripheral blood lymphocytes.
AB  - The present study was conducted on peripheral blood lympho-cytes of rainbow trout
      (Oncorhynchus mykiss) to assess the role of 5-hydroxytryptamine (5-HT;
      'serotonin') in calcium signalling. 5-HT-induced increases in intracellular free
      calcium concentrations, [Ca2+]i, and its action was mediated by 5-HT receptor
      subtype 3 (5-HT3), but not by 5-HT receptor subtype 1A (5-HT1A) or subtype 2 (5
      HT2) in these cells. In Ca2+-containing medium (1 mM CaCl2), 5-HT and 2-methyl-5
      HT (5-HT3 receptor agonist) induced increases in [Ca2+]i, whereas in Ca2+-free
      medium (0 Ca2+, 1 mM EGTA), these two agents failed to evoke increases in [Ca2+]i
      in these cells, demonstrating that 5-HT mobilizes Ca2+ from the extracellular
      environment. Furthermore, 5-HT-induced increases in [Ca2+]i are not contributed
      to by the intracellular endoplasmic reticulum (ER) pool, as thapsigargin, an
      agent that recruits Ca2+ from ER stores, had additive effects on 5-HT-induced
      [Ca2+]i responses in fish peripheral lymphocytes. 5-HT-induced increases in
      [Ca2+]i were mediated by 5-HT3 receptors via gating the calcium through L-type,
      but not N-type, calcium channels in trout lymphocytes.

PMID- 9173892
TI  - The pro region is not required for the expression or intracellular routeing of
      carboxypeptidase E.
AB  - Carboxypeptidase E (CPE) is initially synthesized as a larger precursor
      containing an additional 14-residue propeptide that is highly conserved between
      human and rat. Previous studies have established that the proenzyme is
      enzymically active and that deletion of the pro region does not affect the
      expression of the active enzyme. In the present study the function of the pro
      region was examined both by deleting this region from CPE and by attaching this
      region to the N-terminus of albumin. CPE lacking the pro region is sorted into
      the regulated secretory pathway in AtT-20 cells, based on confocal microscopy and
      examination of the stimulated secretion of the protein. Stimulation of AtT-20
      cells with either forskolin or phorbol 12-myristate 13-acetate induces the
      secretion of wild-type CPE and of CPE lacking the pro region to similar extents,
      indicating a similar efficiency of sorting of the mutant. When the pro region of
      proalbumin is replaced with the pro region of CPE followed by expression in AtT
      20 cells, the protein is not sorted into the regulated pathway, based on the lack
      of stimulated secretion. Confocal microscopy suggests that the proCPE/albumin
      protein is retained in the endoplasmic reticulum to a greater extent than is
      proalbumin. Pulse-chase analysis indicates that the pro region of CPE is not
      efficiently removed from the N-terminus of albumin, and the small amount of
      propeptide cleavage that does occur takes place soon before secretion of the
      protein. In contrast, confocal microscopy indicates that the majority of the
      propeptide is removed from CPE, and that this cleavage occurs in the trans-Golgi
      network or soon after sorting into the secretory vesicles. Taken together, these
      results suggest that the pro region of CPE is not required for the expression or
      intracellular routeing of this protein.

PMID- 9173893
TI  - Intracellular targeting and homotetramer formation of a truncated inositol 1,4,5
      trisphosphate receptor-green fluorescent protein chimera in Xenopus laevis
      oocytes: evidence for the involvement of the transmembrane spanning domain in
      endoplasmic reticulum targeting and homotetramer complex formation.
AB  - In an attempt to define structural regions of the type I inositol 1, 4,5
      trisphosphate [Ins(1,4,5)P3] receptor [Ins(1,4,5)P3R] involved in its
      intracellular targeting to the endoplasmic reticulum (ER), we have employed the
      use of green fluorescent protein (GFP) to monitor the localization of a truncated
      Ins(1,4,5)P3R mutant containing just the putative transmembrane spanning domain
      and the C-terminal cytoplasmic domain [amino acids 2216-2749; termed inositol
      trisphosphate receptor(ES)]. We expressed a chimeric GFP-Ins(1,4, 5)P3R(ES)
      fusion protein in Xenopus laevis oocytes, and used fluorescence confocal
      microscopy to monitor its intracellular localization. Fluorescence confocal
      microscopy data showed an intense fluorescence in the perinuclear region and in a
      reticular-network under the animal pole of the oocyte, consistent with the
      targeting of expressed GFP-Ins(1,4,5)P3R(ES) to perinuclear ER and ER under the
      animal pole. These findings are consistent with the intracellular localization of
      the endogenous Xenopus Ins(1,4, 5)P3R shown previously. Furthermore, electron
      microscopy data indicate that expressed GFP-Ins(1,4,5)P3R(ES) is in fact targeted
      to the ER. Sodium carbonate extraction of microsomal membranes and cross-linking
      experiments indicate that the expressed chimeric protein is in fact membrane
      anchored and able to form a homotetrameric complex. Our data provides evidence
      that Ins(1,4, 5)P3R(ES) constitutes the membrane spanning domain of the Ins(1,4,
      5)P3R and is able to mediate homotetramer formation, without the need for the
      large N-terminal cytoplasmic domain. Furthermore, the localization of GFP
      Ins(1,4,5)P3R(ES) on the ER indicates that an ER retention/targeting signal is
      contained within the transmembrane spanning domain of the inositol trisphosphate
      receptor.

PMID- 9173894
TI  - Cytosolic phospholipase A2 is coupled to muscarinic receptors in the human
      astrocytoma cell line 1321N1: characterization of the transducing mechanism.
AB  - The cholinergic agonist carbachol induced the release of arachidonic acid in the
      1321N1 astrocytoma cell line, and this was blocked by atropine, suggesting the
      involvement of muscarinic receptors. To assess the mechanisms of signalling
      involved in the response to carbachol, a set of compounds characterized by
      eliciting responses through different mechanisms was tested. A combination of
      4beta-phorbol 12beta-myristate 13alpha-acetate and thapsigargin, an inhibitor of
      endomembrane Ca2+-ATPase that induces a prolonged elevation of cytosolic Ca2+
      concentration, induced an optimal response, suggesting at first glance that both
      protein kinase C (PKC) and Ca2+ mobilization were involved in the response. This
      was consistent with the observation that carbachol elicited Ca2+ mobilization and
      PKC-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2; phosphatide
      sn-2-acylhydrolase, EC 3.1.1.4) as measured by a decrease in electrophoretic
      mobility. Nevertheless, the release of arachidonate induced by carbachol was
      unaltered in media containing decreased concentrations of Ca2+ or in the presence
      of neomycin, a potent inhibitor of phospholipase C which blocks phosphoinositide
      turnover and Ca2+ mobilization. Guanosine 5'-[gamma-thio]triphosphate added to
      the cell-free homogenate induced both [3H]arachidonate release and cPLA2
      translocation to the cell membrane fraction in the absence of Ca2+, thus
      suggesting the existence of an alternative mechanism of cPLA2 translocation
      dependent on G-proteins and independent of Ca2+ mobilization. From the
      combination of experiments utilizing biochemical and immunological tools the
      involvement of cPLA2 was ascertained. In summary, these data indicate the
      existence in the astrocytoma cell line 1321N1 of a pathway involving the cPLA2
      which couples the release of arachidonate to the occupancy of receptors for a
      neurotransmitter, requires PKC activity and G-proteins and might operate in the
      absence of Ca2+ mobilization.

PMID- 9173895
TI  - Identification of isoforms of the exocytosis-sensitive phosphoprotein
      PP63/parafusin in Paramecium tetraurelia and demonstration of phosphoglucomutase
      activity.
AB  - PP63 (parafusin) is a 63 kDa phosphoprotein which is very rapidly (within 80 ms)
      dephosphorylated (to P63) during triggered trichocyst exocytosis; this occurs
      selectively in exocytosis-competent Paramecium tetraurelia strains. In the
      present work, two cDNAs coding for PP63/parafusin have been isolated, one of
      which is a new isoform. These isoforms are 99.6% identical and are derived from
      two different genes. Similarity searches revealed 43-51% identity of the deduced
      amino acid sequences with known phosphoglucomutases from yeast and mammals. The
      sequences of two proteolytic peptides obtained from PP63/parafusin isolated from
      Paramecium are identical to parts of the amino acid sequence deduced from the
      major cDNA. The major cDNA was mutated from the macronuclear ciliate genetic code
      into the universal genetic code and expressed in Escherichia coli. The
      recombinant protein shows the same biochemical and immunological characteristics
      as the (P)P63/parafusin originally isolated from Paramecium. It has the same
      specific phosphoglucomutase activity as phosphoglucomutase from chicken muscle.
      We also show that recombinant P63-1 parafusin 1 is a substrate of an endogenous
      casein kinase from Paramecium, as is the originally isolated P63/parafusin.
      Polyclonal antibodies against recombinant P63-1/parafusin 1 were raised which
      recognized phosphoglucomutases from different sources. Thus we show that
      PP63/parafusin and phosphoglucomutase in Paramecium are identical.

PMID- 9173896
TI  - NMR study of the galactomannans of Trichophyton mentagrophytes and Trichophyton
      rubrum.
AB  - Around 90% of chronic dermatophyte infections are caused by the fungi
      Trichophyton mentagrophytes and Trichophyton rubrum. One of the causes of the
      chronic infection resides in the immunosuppressive effects of the cell-wall
      components of these organisms. Therefore we have attempted to identify the
      chemical structure of galactomannan, one of the major cell-wall components. The
      cell-wall polysaccharides secreted by T. mentagrophytes and T. rubrum were
      isolated from the culture medium and fractionated into three subfractions by DEAE
      Sephadex chromatography. Analysis of each subfraction by NMR indicated that there
      are two kinds of polysaccharides present, i.e. mannan and galactomannan. The
      mannan has a linear backbone consisting of alpha1,6-linked mannose units, with
      alpha1,2-linked mannose units as side chains. The core mannan moiety of the
      galactomannan was analysed by a sequential NMR assignment method after removing
      the galactofuranose units by acid treatment. The result indicates that the mannan
      moiety has a linear repeating structure of alpha1,2-linked mannotetraose units
      connected by an alpha1,6 linkage. The H-1 signals of the two intermediary alpha1,
      2-linked mannoses of the tetraose unit showed a significant upfield shift
      (Deltadelta=0.05-0.08 p.p.m.), due to the steric effect of an alpha1,6-linked
      mannose unit. The attachment point of the galactofuranose units was determined at
      C-3 of the core mannan by the assignment of the downfield-shifted 13C signals of
      the galactomannan compared with those of the acid-modified product. In these
      galactomannans there were no polygalactofuranosyl chains which have been found in
      Penicillium charlesii and Aspergillus fumigatus.

PMID- 9173897
TI  - Bufo arenarum egg jelly coat: purification and characterization of two highly
      glycosylated proteins.
AB  - Egg jelly coats from Bufo arenarum are formed by components secreted along the
      oviduct. These secretion products overlay the oocytes as they transit along the
      different oviductal portions. In this study, we have isolated two highly
      glycosylated proteins of the jelly coat, which are secreted almost all the way
      along the oviduct. Both glycoproteins [designated as highly glycosylated protein
      (HGP) and low-molecular-mass highly glycosylated protein (L-HGP)] were purified
      to homogeneity, from the secretion of the caudal oviduct portion, by CsCl density
      gradient ultracentrifugation. HGP is a high-molecular-mass protein with mucin
      like characteristics: high viscosity, a high content of serine and threonine,
      about 70% carbohydrate by weight, and a protease-resistant domain. Cleavage of
      disulphide bridges with reducing agents resulted in the release of a single
      subunit (300000 Da). L-HGP is also a disulphide-cross-linked protein with lower
      apparent monomeric molecular mass, in the range 100-120 kDa and containing 50%
      carbohydrate by weight. HGP contains galactose, fucose, N-acetylgalactosamine and
      sialic acid, but no mannose, suggesting the presence of O-linked oligosaccharides
      exclusively. The secretion ratio of HGP increases from cephalic (16% of total
      protein in pars preconvoluta) to caudal (40% of total protein in pars convoluta)
      oviductal portions. It appears to be the major structural component of the jelly
      coat. Our purification data suggest that HGP is non-covalently linked to the
      other egg jelly proteins. Polyclonal antiserum to each purified glycoprotein from
      secretion was raised in rabbits and used to localize both glycoproteins in the
      different oviductal portions, total egg jelly and the aqueous medium where oocyte
      strings were incubated. HGP forms a stable fibre matrix around the oocyte. L-HGP
      is present in the jelly coat and is released into the incubation medium.

PMID- 9173898
TI  - Prothrombinase is protected from inactivation by tissue factor pathway inhibitor:
      competition between prothrombin and inhibitor.
AB  - The inhibition of prothrombinase by tissue factor pathway inhibitor (TFPI) has
      been studied in the presence and absence of prothrombin. The rate constant of
      association of prothrombinase with full-length TFPI was 2.1x10(7) M-1.s-1 and
      0.05x10(7) M-1.s-1 for the reaction with C-terminus truncated TFPI (TFPI1-161).
      The rate constant of dissociation was 0.65x10(-4) s-1 in both cases. The rate
      constant of inhibition of prothrombinase by TFPI1-161 was similar to that of
      solution-phase factor Xa. In contrast, phospholipids and factor Va enhanced the
      association rate of the reaction between factor Xa and full-length TFPI by
      approx. 20-fold. Although TFPI, and in particular the full-length variant of the
      molecule, is a potent inhibitor of prothrombinase (overall inhibition constant of
      3 pM), we also found that prothrombin competed very effectively with TFPI for the
      active site of factor Xa in the prothrombinase complex. A 50% reduction of the
      rate constant of inhibition was measured in the presence of 4 nM prothrombin,
      i.e. 0.2% of the plasma concentration of prothrombin. The physiological
      significance of TFPI as an inhibitor of prothrombinase activity is thus
      questionable.

PMID- 9173899
TI  - Glutathione transferase mimics: micellar catalysis of an enzymic reaction.
AB  - Substances that mimic the enzyme action of glutathione transferases (which serve
      in detoxification) are described. These micellar catalysts enhance the reaction
      rate between thiols and activated halogenated nitroarenes as well as alpha,beta
      unsaturated carbonyls. The nucleophilic aromatic substitution reaction is
      enhanced by the following surfactants in descending order:
      poly(dimethyldiallylammonium - co - dodecylmethyldiallylammonium) bromide (86/14)
      >>cetyltrimethylammonium bromide>zwittergent 3-16 (n-hexadecyl-N,N-dimethyl-3
      ammonio-1-propanesulphonate)>zwittergent+ ++ 3-14 (n-tetradecyl-N,N-dimethyl - 3 
      ammonio -1 - propanesulphonate) approximately N,N - dimethyl - laurylamine N
      oxide>N,N-dimethyloctylamine N-oxide. The most efficient catalyst studied is a
      polymeric material that incorporates surfactant properties (n
      dodecylmethyldiallylammonium bromide) and opens up possibilities for engineering
      sequences of reactions on a polymeric support. Michael addition to alpha,beta
      unsaturated carbonyls is exemplified by a model substance, trans-4-phenylbut-3-en
      2-one, and a toxic compound that is formed during oxidative stress, 4-hydroxy-2
      undecenal. The latter compound is conjugated with the highest efficiency of those
      tested. Micellar catalysts can thus be viewed as simple models for the
      glutathione transferases highlighting the influence of a positive electrostatic
      field and a non-specific hydrophobic binding site, pertaining to two catalytic
      aspects, namely thiolate anion stabilization and solvent shielding.

PMID- 9173900
TI  - Identification of the epitope for a monoclonal antibody that blocks platelet
      aggregation induced by type III collagen.
AB  - A library of eight conformation-dependent monoclonal antibodies that react with
      distinct epitopes on native human type III collagen has been examined for the
      ability of these antibodies to inhibit platelet aggregation induced by this
      collagen. Six of these antibodies had no effects; one, 1E7-D7/Col3, delayed the
      onset and slowed the rate of platelet aggregation, while another, 2G8-B1/Col3,
      completely inhibited aggregation. In order to identify the epitope recognized by
      this inhibitory antibody, a series of peptides that could fold to form triple
      helical fragments was examined. Each peptide included six Gly-Xaa-Yaa triplets
      from the human type III collagen sequence, where Xaa and Yaa represent the
      particular amino acids in the sequence, and a C-terminal (Gly-Pro-Hyp)4 sequence
      to enhance triple-helical stability. Using these peptides we have identified the
      epitope as a nine-amino-acid sequence, GLAGAOGLR (where O is the one-letter code
      for 4-hydroxyproline), starting at position 520 in the human type III collagen
      helical domain. This sequence is proximal to the site proposed for the
      interaction of type III collagen with alpha2beta1-integrin of platelets.

PMID- 9173902
TI  - Identification of amino acid residues responsible for differences in substrate
      specificity and inhibitor sensitivity between two human liver dihydrodiol
      dehydrogenase isoenzymes by site-directed mutagenesis.
AB  - Human liver dihydrodiol dehydrogenase isoenzymes (DD1 and DD2), in which only
      seven amino acid residues are substituted, differ remarkably in specificity for
      steroidal substrates and inhibitor sensitivity: DD1 shows 20alpha-hydroxysteroid
      dehydrogenase activity and sensitivity to 1,10-phenanthroline, whereas DD2
      oxidizes 3alpha-hydroxysteroids and is highly inhibited by bile acids. In the
      present study we performed site-directed mutagenesis of the seven residues (Thr
      38, Arg-47, Leu-54, Cys-87, Val-151, Arg-170 and Gln-172) of DD1 to the
      corresponding residues (Val, His, Val, Ser, Met, His and Leu respectively) of
      DD2. Of the seven mutations, only the replacement of Leu-54 with Val produced an
      enzyme that had almost the same properties as DD2. No significant changes were
      observed in the other mutant enzymes. An additional site-directed mutagenesis of
      Tyr-55 of DD1 to Phe yielded an inactive protein, suggesting the catalytically
      important role of this residue. Thus a residue at a position before the catalytic
      Tyr residue might play a key role in determining the orientation of the
      substrates and inhibitors.

PMID- 9173901
TI  - N-terminal type I modules required for fibronectin binding to fibroblasts and to
      fibronectin's III1 module.
AB  - Assembly of fibronectin fibrils occurs at the surface of substrate-attached cells
      and is mediated by the first to the fifth type I modules in the N-terminal 70 kDa
      portion of the molecule. The first type III module (III1) of fibronectin, not
      present in the 70 kDa portion, contains a conformation-dependent binding site for
      the 70 kDa N-terminal region of fibronectin, suggesting that the III1 module on
      cell-surface fibronectin may serve as a binding site for fibronectin's N-terminus
      on substrate-attached cells. To explore this possiblility, we compared the
      ability of mutant recombinant 70 kDa proteins containing deletions of one or
      several of the first five type I modules to bind to fibroblasts and to III1.
      Proteins containing the fourth and fiftBiomolecular Chemistry and Medicine,
      University of Wisconsin, Madison, WI 53706U.S.A. Assembly of fibronectin fibrils
      occurs at the surface of substrate-attached cells and is mediated by the first to
      the fifth type I modules in the N-terminal 70 kDa portion of the molecule. The
      first type III module (III1) of fibronectin, not present in the 70 kDa portion,
      contains a conh as 70 kDa deletion mutants lacking I4 and I5 also bound to the
      cell surface, and deletion mutants lacking I1-3 and I4-5 both competed only
      partially for binding of 125I-labelled fibronectin or 70 kDa protein. These data
      indicate that the N-terminal part of fibronectin binds to III1 via I4 and I5 and
      that interactions in addition to that of I4 and I5 with III1 are important for
      cell-surface-mediated fibronectin polymerization.

PMID- 9173903
TI  - Purification and characterization of three constitutive cytochrome P-450 isoforms
      from bovine olfactory epithelium.
AB  - Three constitutive forms of cytochrome P-450 (P-450s) were isolated from
      olfactory microsomes of cattle. The purified P-450s, designated P-450bov1, P
      450bov2 and P-450bov3, were electrophoretically nearly homogeneous by SDS/PAGE
      and their apparent relative molecular masses were estimated to be 50000, 53000
      and 51000 respectively. As indicated by several criteria including the N-terminal
      sequence and absorption spectra, the three olfactory forms of P-450 were distinct
      from each other and from all the other P-450s currently known in cattle. P
      450bov1 and P-450bov2 were purified in the low-spin state, whereas P-450bov3 was
      in the high-spin state. Studies to evaluate, by Western blot analysis, the
      reactivity of these purified P-450s with antibodies raised against rat hepatic P
      450 2E1, 2B, 1A and 3A and rabbit olfactory P-450NMa and P-450NMb showed that P
      450bov3 strongly cross-reacted with anti-P-450NMb IgG, and P-450bov1 moderately
      with anti-P-450NMa IgG. As determined by immunoblots, P-450bov1 and P-450bov3
      represented a great portion of the total olfactory P-450. In a reconstituted
      system with NADPH:cytochrome P-450 reductase and phospholipids, P-450bov1 was
      more active in the metabolism of xenobiotic compounds (i.e. O-de-ethylation of
      ethoxycoumarin and N-demethylation of hexamethylphosphoramide) than towards
      endogenous substrates (testosterone and progesterone). Conversely, P-450bov3
      metabolized the xenobiotics at lower rates but exhibited total oxidation rates of
      the above sex hormones higher than those of P-450bov1. From the comparison of the
      catalytic, immunochemical and structural properties, it was inferred that P
      450bov1 and P-450bov3 are the bovine orthologues of P-450NMa (2A) and P-450NMb
      (2G1) respectively, the only two olfactory P-450s previously purified from
      rabbit. P-450bov2, which showed low activity toward some exogenous and endogenous
      compounds, represents a novel purified olfactory hemoprotein possibly belonging
      to the 3A subfamily. These results are consistent with a specific presence of
      catalytically and structurally similar P-450s, at least for the major ones, in
      the olfactory mucosa of mammals.

PMID- 9173904
TI  - Inhibition of rabbit muscle aldolase by phosphorylated aromatic compounds.
AB  - The interactions of the phosphorylated derivatives of hydroquinone (HQN-P2),
      resorcinol (RSN-P2), 4-hydroxybenzaldehyde (HBA-P) and 2, 4-dihydroxybenzaldehyde
      (DHBA-P; phosphate group at position 4) with fructose bisphosphate aldolase were
      analysed by enzyme kinetics, UV/visible difference spectroscopy and site-directed
      mutagenesis. Enzyme activity was competitively inhibited in the presence of HQN
      P2, RSN-P2 and HBA-P, whereas DHBA-P exhibited slow-binding inhibition.
      Inhibition by DHBA-P involved active-site Schiff-base formation and required a
      phenol group ortho to the aldehyde moiety. Rates of enzyme inactivation and of
      Schiff-base formation by DHBA-P were identical, and corresponded to 3.2-3.5 DHBA
      P molecules covalently bound per aldolase tetramer at maximal inactivation. Site
      directed mutagenesis of the active-site lysine residues at positions 107, 146 and
      229 was found to be consistent with Schiff-base formation between DHBA-P and Lys
      146, and this was promoted by Lys-229. Mutation of Glu-187, located vicinally
      between Lys-146 and Lys-229 in the active site, perturbed the rate of Schiff-base
      formation, suggesting a functional role for Glu-187 in Schiff-base formation and
      stabilization. The decreased cleavage activity of the active-site mutants towards
      fructose 1, 6-bisphosphate is consistent with a proton-transfer mechanism
      involving Lys-229, Glu-187 and Lys-146.

PMID- 9173905
TI  - Interactions of the zinc-regulated factor (ZiRF1) with the mouse metallothionein
      Ia promoter.
AB  - A mouse cDNA clone, M96, encoding a metal-regulating-element (MRE)-binding
      protein, was analysed for its ability to act as a metal-regulated transcription
      factor. The metal depletion of a glutathione S-transferase (GST)-M96 fusion
      protein showed that Zn2+ ions modulate the MRE-binding activity, suggesting that
      the M96-encoded protein is a Zn2+-regulated factor (ZiRF1). The methylation
      interference assay showed the specific interactions of ZiRF1 with the MRE,
      MREd/c, present on the mouse metallothionein Ia promoter. Point mutations of the
      MREd/c nullified the metal-regulatory properties of this region. In mouse L-cell
      nuclear extracts, mobility-shift assays revealed a Zn2+-dependent MRE-binding
      complex (MBC) with DNA-recognition properties similar to those of ZiRF1.
      Antibodies raised against purified GST-ZiRF1 were able to specifically recognize
      MBC in Western-blot analyses. Competition analysis of MRE-binding proteins from
      mouse NIH3T3 cells with oligonucleotide matching the binding sites for SP1 and
      MTF1 confirmed that both the basal SP1 and the metal-regulated MBC/ZiRF1 interact
      with the MREd/c region. The significance of mutual interactions with the metal
      responsive promoter regions of either metal-regulated or basal transcription
      factors is discussed.

PMID- 9173907
TI  - [3Fe-4S] <--> [4Fe-4S] cluster interconversion in Desulfovibrio africanus
      ferredoxin III: properties of an Asp14 --> Cys mutant.
AB  - The 8Fe ferredoxin III from Desulfovibrio africanus is a monomeric protein which
      contains two [4Fe-4S]2+/1+ clusters, one of which is labile and can readily and
      reversibly lose one Fe under oxidative conditions to yield a [3Fe-4S]1+/0
      cluster. This 4Fe cluster has an S = 3/2 ground sping state insteaed of S = 1/2
      in the reduced +1 state [George, Armstrong, Hatchikian and Thomson (1989)
      Biochem. J. 264, 275-284]. The co-ordination to this cluster is unusual in that
      an aspartate (Asp14, D14, is found where a cysteine residue normally occurs.
      Using a mutant protein obtained from the overexpression in Escherichia coli of a
      synthetic gene in which Asp14, the putative ligand to the removable Fe, has been
      changed to Cys, we have studied the cluster interconversion properties of the
      labile cluster. Analysis by EPR and magnetic-circular-dichroism spectroscopies
      showed that the Asp14 --> Cys (D14C) mutant contains two [4Fe-4S]2+/1+ clusters,
      both with S = 1/2 in the reduced state. Also, unlike in native 8Fe D. africanus
      ferredoxin III, the 4Fe <--> 3Fe cluster interconversion reaction was found to be
      sluggish and did not go to completion. It is inferred that the reversibility of
      the reaction in the native protein is due to the presence of the aspartate
      residue at position 14 and that this residue might protect the [3Fe-4S] cluster
      from further degradation.

PMID- 9173906
TI  - Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase
      occurs upstream of Ca2+-signalling induced by Fcgamma receptor cross-linking in
      human neutrophils.
AB  - The effect of wortmannin on IgG-receptor (FcgammaR)-mediated stimulation of human
      neutrophils was investigated. The Ca2+ influx induced by clustering of both
      Fcgamma receptors was inhibited by wortmannin, as was the release of Ca2+ from
      intracellular stores. Wortmannin also inhibited, with the same efficacy, the
      accumulation of Ins(1,4,5)P3 observed after FcgammaR stimulation, but did not
      affect the increase in Ins(1,4,5)P3 induced by the chemotactic peptide, formyl
      methionine-leucine-phenylalanine. Because wortmannin is, in the concentrations
      used here, an inhibitor of PtdIns 3-kinase, these results suggested a role for
      PtdIns 3-kinase upstream of Ca2+ signalling, induced by FcgammaR cross-linking.
      Support for this notion was obtained by investigating the effect of another
      inhibitor of PtdIns 3-kinase, LY 294002, and by studying the kinetics of PtdIns 3
      kinase activation. We found translocation of PtdIns 3-kinase to the plasma
      membrane and increased PtdIns 3-kinase activity in the membrane as soon as 5 s
      after FcgammaR cross-linking, even before the onset of the Ca2+ response.
      Moreover, the translocation of PtdIns 3-kinase to the plasma membrane was
      inhibited by co-cross-linking of either FcgammaRIIa and FcgammaRIIIb with the
      tyrosine phosphatase, CD45, indicating a requirement for protein tyrosine
      phosphorylation in the recruitment of PtdIns 3-kinase to the plasma membrane.
      Taken together, our results suggest a role for PtdIns 3-kinase in early signal
      transduction events after FcgammaR cross-linking in human neutrophils.

PMID- 9173909
TI  - Neurobiology of Huntington's disease.

PMID- 9173910
TI  - Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down
      syndrome: implications for initial events in amyloid plaque formation.
AB  - Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta
      protein (A beta) deposits and then other features of Alzheimer's disease (AD),
      apparently due to increased gene dosage and thus expression of the beta-amyloid
      precursor protein. Because the neuropathological phenotype in older DS subjects
      closely resembles that of AD, the examination of DS brains of increasing age
      provides a unique model of the progression of AD. Here, we characterized the
      deposition of several A beta peptides and apolipoprotein E in formalin-fixed
      brain sections from 29 DS subjects between 3 and 73 years old. Amyloid plaque
      number and the percentage of cortical area they occupied were quantified by
      computerized image analysis. A beta ending at amino acid 42 (A beta 42) was the
      earliest form of A beta deposited in DS cortex. It was observed in 7 of 16 young
      (3-30 years) subjects, with the earliest deposition occurring at age 12. A beta
      ending at residue 40 (A beta 40) was not detected until approximately age 30, a
      time when degenerating neurites around A beta immunoreactive (IR) plaques were
      first observed, and the frequency of A beta 40 IR plaques then rose with age.
      Even in old (51-73 years) DS subjects, A beta 42 IR plaques were always more
      abundant than A beta 40 IR plaques. A beta peptides starting at aspartate 1 or
      pyroglutamate 3 were detected in small subsets of compacted, neuritic plaques
      beginning around age 30 and rose with age, the latter species always exceeding
      the former. Thus, the N-termini of the A beta 42 peptides abundantly deposited in
      very young DS subjects remain unknown. Apo E was detectable in a small subset of
      A beta 42 IR plaques beginning at age 12 and rose steadily with age; it clearly
      followed the deposition of A beta. Our analysis of very young DS brains suggests
      that amyloid plaque formation begins with A beta 42-ending peptides, and the
      number and percentage of cortical area of A beta 42 plaques increase very little
      with advancing age, while other heterogeneous A beta species and Apo E
      progressively accrue onto plaques containing A beta 42.

PMID- 9173911
TI  - Conditionally immortalized neural progenitor cells grafted to the striatum
      exhibit site-specific neuronal differentiation and establish connections with the
      host globus pallidus.
AB  - The cell line RN33B has been reported to differentiate into neurons in a site
      specific manner when grafted to the cortex and hippocampus of adult rats. To
      investigate the fate of RN33B cells in a subcortical structure, we grafted RN33B
      cells into the intact or excitoxically lesioned striatum of adult or neonatal
      rats. The total number and phenotypic characteristics of the [3H]thymidine
      labeled grafted cells were analyzed at different time points after
      transplantation. Transplanted RN33B cells were found to survive, integrate, and
      differentiate into both neurons and astrocytes, and a significant proportion of
      the cells (approx. 10%) were found to differentiate into cells with morphological
      and phenotypic characteristics of medium-sized striatal projection neurons.
      Retrograde tracing showed that at least some of the graft-derived neurons were
      capable of establishing connections with one of the primary striatal targets, the
      globus pallidus. These findings demonstrate a remarkable capacity of the RN33B
      cells for site-specific neuronal differentiation in both the adult and the
      developing striatum and suggest that the same differentiating factors that are
      operating during normal neurogenesis in brain development are retained, at least
      to some extent, also in the adult CNS.

PMID- 9173912
TI  - Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's
      disease brain.
AB  - Phospholipase A2 (PLA2) is the key enzyme that initiates the arachidonic acid
      cascade, which leads to the generation of multiple eicosanoid products. Many of
      these products are believed to play an important role in the inflammatory
      process. Activation of PLA2 is observed under pathological conditions where
      inflammation is present. Cytosolic PLA2 (cPLA2) is activated by very low levels
      of calcium and is thought to control receptor-mediated eicosanoid production and
      to participate in intracellular signal transduction processes. In view of the
      presence of numerous inflammatory mediators and acute phase proteins in the
      Alzheimer's disease (AD) brain, localization of cPLA2 in AD brain was evaluated
      and compared to that observed in nonneurologically diseased controls. In this
      study, a monoclonal antibody raised against cPLA2 was used to immunostain tissue
      sections of human cerebral cortex. Five AD cases and six neurologically normal
      cases were evaluated in the occipital cortex and the cerebellum. Two of the AD
      cases were also examined in other cortical regions. Granular-like staining with
      anti-cPLA2 was found to be associated with astrocytes in the cortex of both
      control and AD cases. Colocalization with GFAP confirmed that cPLA2
      immunoreactivity is associated almost exclusively with protoplasmic astrocytes.
      Staining was abolished when sections were labeled with antibody that had been
      preadsorbed with purified cPLA2. In AD brain, cPLA2 immunoreactive astrocytes
      were greater in number and more intensely stained than those in control cases.
      cPLA2 immunoreactivity was virtually absent in the cerebelium of AD and control
      cases, despite the presence in this region of diffuse amyloid in two AD cases and
      amyloid angiopathy in a third case. In the cortex, cPLA2 immunoreactive
      astrocytes were detected in regions that contained numerous A beta deposits. The
      finding of elevated levels of cPLA2 immunoreactivity in AD brain supports the
      hypothesis that there is an active inflammatory process occurring in AD.

PMID- 9173913
TI  - Neonatal mice lacking neuronal nitric oxide synthase are less vulnerable to
      hypoxic-ischemic injury.
AB  - We hypothesized that elimination of neuronal nitric oxide synthase (nNOS) by
      targeted disruption of the nNOS gene would result in amelioration of damage seen
      after hypoxia-ischemia in the developing brain since nitric oxide (NO) has been
      implicated in glutamate-mediated neurotoxicity after ischemia. Both wildtype and
      nNOS-deficient pups were subjected to focal ischemia followed by 1.5 h of hypoxia
      at Postnatal Day 7. Seven days later, brains of surviving animals were analyzed
      for damage. The nNOS-deficient pups (n = 17) had less histopathologic evidence of
      injury in both the hippocampus (P = 0.008) and the cortex (P = 0.0008) than the
      wildtype (n = 30) mice. When injured, the nNOS-deficient mice had damage that was
      limited to the hippocampus. These results support a role for neuronally produced
      NO in injury after perinatal hypoxia-ischemia.

PMID- 9173914
TI  - NADPH diaphorase-containing striatal or cortical neurons are resistant to
      apoptosis.
AB  - The small subpopulation of striatal neurons containing nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d, recently identified as nitric oxide
      synthase, NOS) is selectively spared in Huntington's disease. Previous search for
      pathogenic mechanisms capable of destroying striatal neurons but sparing NADPH
      d(+) cells has identified only NMDA receptor-mediated excitotoxicity. In view of
      suggestions that neuronal death in Huntington's disease may occur by apoptosis,
      we examined the vulnerability of NADPH-d(+) neurons to apoptosis. Murine striatal
      or cortical cultures exposed to serum deprivation developed extensive neuronal
      apoptosis, but NADPH-d(+) neurons were relatively spared. This sparing was seen
      when cultures were exposed to several other apoptosis-inducing insults. It was
      not seen after toxic exposure to H2O2, and it was not blocked by NOS inhibition.
      The selective resistance of NADPH-d(+) neurons to several forms of apoptosis
      provides key support for the possibility that apoptosis may contribute to the
      pathogenesis of Huntington's disease.

PMID- 9173915
TI  - Direct intracerebral nerve growth factor gene transfer using a recombinant
      adenovirus: effect on basal forebrain cholinergic neurons during aging.
AB  - Gene therapy in the nervous system offers an attractive strategy for the
      administration of therapeutic factors in a potentially region-specific,
      sustained, and well-tolerated manner. We tested the trophic effect of a
      recombinant adenovirus encoding nerve growth factor (AdNGF) in vivo on basal
      forebrain cholinergic neurons of aged rats, a neuronal population affected during
      normal and pathological aging. Three weeks after unilateral injection of the
      recombinant adenovirus into the nucleus basalis magnocellularis, a significant
      increase in the somal areas of cholinergic neurons ipsilateral to the injection
      was observed. No increase was detected in animals receiving a recombinant
      adenovirus carrying the Escherichia coli Lac Z reporter gene. Injected animals
      did not lose weight, an adverse effect usually described after
      intracerebroventricular infusion of NGF, and no tissue loss or massive local
      inflammatory response was observed around injection sites. Thus, a single
      intracerebral injection of AdNGF produces trophic effects similar to those
      resulting from chronic intracerebroventricular high levels of NGF. These findings
      indicate that recombinant adenoviruses encoding growth factors are potentially
      powerful tools for improving neuronal deficits associated with degenerative
      processes.

PMID- 9173916
TI  - A chimeric analysis of the opioid receptor domains critical for the binding
      selectivity of mu opioid ligands.
AB  - The mu opioid receptor plays a key role in mediating the physiological,
      pharmacological, and behavioral effects of endogenous opioids and of opiate drugs
      such as morphine and heroin. This study examines the structural features critical
      to the selective binding of mu ligands to the mu receptor as opposed to the other
      two highly homologous opioid receptors, delta and kappa. We use a series of
      chimeric constructs between the mu and either the delta or the kappa receptors to
      investigate the structural bases of binding selectivity of multiple classes of mu
      selective ligands. Our results demonstrate that a region comprising the sixth
      transmembrane domain and the third extracellular loop is critical for the
      mu/kappa discrimination by all mu-selective ligands. This region is also critical
      for mu/delta discrimination by the mu antagonists. However, mu agonists,
      particularly the peptides, exhibit more complex interactions, often relying on
      the N-terminal region surrounding the first extracellular loop for mu/delta
      discrimination. Thus, the same mu peptide ligand depends on different parts of
      the receptor to discriminate between mu and delta receptors on the one hand and
      mu and kappa on the other. In general, antagonists show the most consistent
      discrimination mechanisms regardless of construct, whereas agonists, particularly
      peptides, achieve selectivity by interacting with numerous domains of the
      receptors.

PMID- 9173917
TI  - The neurobiology of childhood spinal muscular atrophy.

PMID- 9173918
TI  - Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and
      developing nervous system tissues.
AB  - Tuberous sclerosis (TS) is an autosomal dominant disorder in which affected
      individuals manifest mental retardation, seizures, and a variety of benign and
      malignant tumors. The TSC2 tumor suppressor gene was recently identified by
      positional cloning and its protein product, tuberin, shown to represent one
      member of the rap GTPase activating protein (rapGAP) family. In order to
      determine the contribution of tuberin to the development of mental retardation
      and seizures in patients with TS, we examined the expression of tuberin in adult
      and developing nervous system tissues. Since tuberin is the second rapGAP found
      in the nervous system, the expression of tuberin was compared to the expression
      of rapGAP, rap1, and rap2. In this study, we demonstrate that tuberin is
      expressed at greatest levels in the spinal cord and cerebellum as opposed to
      rapGAP, which is not enriched in these tissues. Tuberin expression in the adult
      CNS is restricted to the olfactory bulb, several CNS neuronal populations,
      brainstem nuclei, cerebellar Purkinje cells, and motor neurons in the ventral
      spinal cord. In contrast, rapGAP is expressed in many different cell types in the
      adult CNS, but not in cerebellar Purkinje cells or motor neurons in the ventral
      spinal cord. However, there is significant expression of rapGAP in astrocytes.
      The restricted distribution of tuberin expression relative to rap1 and rapGAP
      suggests that tuberin may be the primary rap1 regulator in a subpopulation of CNS
      neurons.

PMID- 9173919
TI  - cDNA cloning and characterization of an atrophin-1 (DRPLA disease gene)-related
      protein.
AB  - Dentatorubral and pallidoluylsian atrophy (DRPLA) is a progressive neurological
      disorder characterized by neuronal degeneration, especially in the cerebellar
      dentate nucleus. DRPLA is caused by an unstable expansion of a CAG trinucleotide
      repeat coding for glutamine in a gene of unknown function, termed atrophin-1,
      located on chromosome 12. To gain additional understanding of atrophin-1, we have
      isolated a second member of the atrophin-1 gene family by screening rat cDNA
      libraries. The 1006-amino-acid product of this gene, which we have termed rat
      atrophin related protein(rARP), does not contain a glutamine repeat, but it does
      contain two regions of alternating acidic and basic amino residues similar to
      those found in atrophin-1. rARP is widely expressed as both a 7.4- and a 9.4-kb
      message, with enrichment in cerebellum and testis. Like atrophin-1, the rARP in
      vitro translation product migrates more slowly on SDS-polyacrylamide gel
      electrophoresis than predicted by molecular weight. We conclude that, at least in
      the rat, polyglutamine is not an essential feature of the atrophin family of
      genes.

PMID- 9173920
TI  - Buckminsterfullerenol free radical scavengers reduce excitotoxic and apoptotic
      death of cultured cortical neurons.
AB  - Novel anti-oxidants based on the buckminsterfullerene molecule were explored as
      neuroprotective agents in cortical cell cultures exposed to excitotoxic and
      apoptotic injuries. Two polyhydroxylated C60 derivatives, C60(OH)n, n = 12, and
      C60(OH)nOm, n = 18-20, m = 3-7 hemiketal groups, demonstrated excellent anti
      oxidant capabilities when tested by electron paramagnetic spectroscopy with a
      spin-trapping agent and a hydroxyl radical-generating system. These water-soluble
      agents decreased excitotoxic neuronal death following brief exposure to NMDA (by
      80%), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA; by 65%),
      or kainate (by 50%). Electrophysiology and tracer 45Ca(2+)-uptake studies
      verified that buckminsterfullerenois are not NMDA or AMPA/kainate receptor
      antagonists. Buckminsterfullerenols also reduced neuronal apoptosis induced by
      serum deprivation. These results support the idea that oxidative stress
      contributes to both excitotoxic and apoptotic neuronal death, and furthermore
      suggest that fullerenols represent a novel type of biological anti-oxidant
      compound.

PMID- 9173921
TI  - Electromyographical and motor performance studies in the pmn mouse model of
      neurodegenerative disease.
AB  - The mouse autosomal recessive mutation progressive motor neuronopathy (pmn)
      results in early onset motor neuron disease with rapidly progressive hindlimb
      paralysis, severe muscular wasting, and death at around 6 weeks of age. This
      mutant provides opportunities for testing novel therapeutic strategies, including
      the administration of trophic factors, to prevent the degeneration of diseased
      neurons. The construction of a strain expressing the pmn and the Extra-toe (Xt)
      phenotypes allows the detection, and therefore the treatment, of affected progeny
      before the onset of the clinical weakness. Electromyography is the most
      appropriate technique for a longitudinal study in which a given individual is
      examined repeatedly. We present the results of an electrophysiological and
      behavioral exploration of the pmn disease and show that electromyography is a
      powerful tool for following the course of the disease and evaluating potential
      therapies relevant to motor neuron diseases.

PMID- 9173922
TI  - Delayed treatment with alpha-phenyl-N-tert-butyl nitrone (PBN) attenuates
      secondary mitochondrial dysfunction after transient focal cerebral ischemia in
      the rat.
AB  - The present experiments were undertaken to explore the mechanisms of secondary
      brain damage in focal ischemia of long duration (2 h), followed by recirculation.
      Recirculation has previously been found to cause partial recovery and secondary
      deterioration of cellular bioenergetic state, the subsequent damage being
      ameliorated by a free radical spin trap, alpha-phenyl-N-tert-butyl nitrone (PBN),
      even when the drug was given 1 (or 3) h after the start of recirculation. Our
      objective was to assess whether the secondary deterioration of the cellular
      bioenergetic state is due to mitochondrial dysfunction and to study whether PBN
      acts by preventing secondary damage to mitochondria. Focal and perifocal
      ("penumbral") tissues were sampled after 2 h of ischemia and after 1, 2, and 4 h
      of recirculation; at the latter two times, vehicle- and PBN-injected animals were
      studied, PBN being given after 1 h of recirculation. Homogenates were prepared,
      and stimulated (+ADP), nonstimulated (-ADP), and uncoupled respiratory rates were
      measured polarographically. The results were similar in focus and penumbra,
      albeit more pronounced in the focus. Ischemia was associated with a decrease in
      ADP-stimulated and uncoupled respiration rates, with a marked fall in the
      respiratory control ratio, defined as ADP-stimulated divided by nonstimulated
      respiration. Recirculation (1 h) brought about partial recovery, but continued
      reflow (2 and 4 h) was associated with a secondary deterioration of respiratory
      functions. This deterioration was prevented by PBN, given 1 h after the start of
      recirculation. The results raise the question whether the secondary deterioration
      of the cellular bioenergetic state in focal ischemia-reperfusion is due to
      secondary mitochondrial dysfunction and whether the amelioration of the
      subsequent damage by PBN is partly or wholly due to the effect of the spin trap
      on the mitochondria.

PMID- 9173923
TI  - Molecular insights into neurofibromatosis 2.

PMID- 9173924
TI  - Interleukin-1alpha in the brain is induced by audiogenic seizure.
AB  - We examined the expression of the sleep-inducing cytokine interleukin-1alpha (IL
      1alpha) in the brains of audiogenic seizure-susceptible mice subsequent to the
      induction of sound-induced seizure. Animal models of epilepsy often require
      lesioning or trauma that may nonspecifically alter IL-1alpha expression. To avoid
      this, we employed the Frings mouse strain; a model of auditory-evoked reflex
      epilepsy. Frings mice were exposed to a high-intensity sound stimulus to induce a
      tonic extension seizure, and the expression of IL-1alpha transcripts in different
      brain regions was measured thereafter. Compared to control animals, IL-1alpha
      transcripts were elevated 6 to 8 h postseizure in the hypothalamus, but not
      hippocampus, by a dexamethasone-sensitive pathway. Similar results were obtained
      from the genetically distinct DBA/2J audiogenic seizure-susceptible mouse strain.
      These findings demonstrate that the expression of IL-1alpha is altered following
      generalized seizure activity, induced by noninvasive sensory stimulation, in a
      brain-region-specific manner.

PMID- 9173925
TI  - Expression of the adrenoleukodystrophy protein in the human and mouse central
      nervous system.
AB  - The gene mutated in X-linked adrenoleukodystrophy (ALD), a progressive
      demyelinating disease, codes for a protein (ALDP) involved in very-long-chain
      fatty acid (VLCFA) transport. The expression of ALDP and of two peroxisomal
      enzymes involved in beta-oxidation of VLCFA, acyl-CoA oxidase, and catalase was
      studied in human and mouse brain. The pattern of expression was similar in both
      species. While acyl-CoA oxidase and catalase are found in all types of CNS cells,
      including neurons and oligodendrocytes, ALDP expression is restricted mostly to
      the white matter and endothelial cells. ALDP is highly expressed in astrocytes
      and microglial cells in vivo and in regenerating oligodendrocytes in vitro. In
      contrast, in vivo, ALDP is detected in much fewer oligodendrocytes and
      quantitative Western blot analysis confirmed the lower abundance of ALDP in these
      cells than in astrocytes. Only oligodendrocytes localized in corpus callosum,
      internal capsules, and anterior commissure express ALDP at levels comparable to
      those seen in astrocytes. In ALD, demyelination is first detected in these white
      matter regions, suggesting that the ALD gene mutation selectively affects those
      oligodendrocytes strongly expressing ALDP. Because of their failure to express
      ALDP, microglia and astrocytes may also contribute to demyelination in ALD
      patients.

PMID- 9173926
TI  - Mitochondrial morphology and intracellular calcium homeostasis in cytochrome
      oxidase-deficient human fibroblasts.
AB  - Mitochondrial encephalomyopathies arise from mutations in the mitochondrial or
      nuclear genome and result in defective energy metabolism. Investigation of
      cellular pathophysiology in these disorders has been limited to nonneuronal
      explant cultures such as fibroblasts and myoblasts. While investigating
      mitochondrial structure and function in fibroblasts obtained from control and
      cytochrome oxidase-deficient (COX) patients, we observed possible abnormalities
      by vital dye confocal microscopy. Most notable were swelling, reticulation (e.g.,
      intricate fusion of mitochondria), and proliferation of mitochondria. However, a
      detailed quantitative comparison of mitochondrial morphology in age-, sex-, and
      passage-matched cultures revealed no significant differences between control and
      cytochrome oxidase-deficient fibroblasts, nor any differences with passage. In
      addition, COX fibroblasts exhibited no obvious impairment of intracellular
      calcium handling, measured by fura-2. These results indicate that cytochrome
      oxidase deficiency, at the level in these cultures, does not produce structural
      or ionic concentration alterations in fibroblasts. Future investigation of the
      pathophysiology of this respiratory chain disorder may require excitable tissue.

PMID- 9173927
TI  - Developmental features of human striatal tissue transplanted in a rat model of
      Huntington's disease.
AB  - Areas of striatal grafts which contain neurons that are characteristic of the
      striatum are called P-zones. We have investigated whether the paucity of P-zones
      in human xenografts of lateral ganglionic eminence (LGE) tissue in a rat model of
      Huntington's disease is due (i) to an absence of the appropriate target cells of
      LGE neurons or (ii) to the persistence of an immature morphology. Striatal tissue
      from human embryos of varying sizes (21, 24, and 30 mm in crown-to-rump length)
      was grafted into the ibotenate-lesioned striatum of immunosuppressed rats, which
      were killed after 15-17 weeks. In most cases, tissue from the LGE and medial
      ganglionic eminence (MGE) was transplanted together, whereas some rats received
      grafts of only LGE tissue. Both types of grafts exhibited positive immunostaining
      for PCNA (proliferating cells), Vimentin (immature astrocytes), and GAP-43
      (outgrowing fibers), which indicates that graft maturation is still ongoing up to
      4 months after grafting. Graft survival seemed better when MGE was cografted with
      LGE, suggesting that the MGE may provide trophic support for LGE neurons and can
      affect the overall survival of human striatal xenografts. However, the extent of
      P-zone formation was not increased in MIXED, i.e., LGE plus MGE, grafts.

PMID- 9173928
TI  - Characterization of an expanded glutamine repeat androgen receptor in a neuronal
      cell culture system.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an inherited form of lower motor
      neuron degeneration caused by expansion of a CAG repeat in the androgen receptor
      (AR) gene. To study the mechanism by which this mutation causes neuronal
      pathology, we stably transfected a motor neuron hybrid cell line with human AR
      cDNAs containing either 24 or 65 repeats (AR24 and AR65, respectively). Both
      forms of receptor were able to bind ligand and activate transcription of a
      reporter construct equally well. Likewise, the subcellular localizations of AR24
      and AR65 were similar, in both the presence and the absence of ligand. AR24- and
      AR65-expressing clones were phenotypically indistinguishable. They survived
      equally well after differentiation and were equally susceptible to damage by
      oxidative stress. Our studies thus demonstrate that, in a neuronal system, the
      expanded repeat AR functions like the normal repeat AR in several important ways.
      Because levels of AR65 expression were consistently lower than levels of AR24
      expression, we propose that the loss of function of AR seen in SBMA may be due to
      decreased levels of receptor expression rather than to a difference in intrinsic
      properties. The postulated gain of function responsible for neuronal degeneration
      remains to be determined.

PMID- 9173929
TI  - Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and
      Ala299 and occur as stable N- and C-terminal fragments in normal and Alzheimer
      brain tissue.
AB  - Humans inheriting missense mutations in the presenilin (PS)1 and -2 genes undergo
      progressive cerebral deposition of the amyloid beta-protein at an early age and
      develop a clinically and pathologically severe form of familial Alzheimer's
      disease (FAD). Because PS1 mutations cause the most aggressive known form of AD,
      it is important to elucidate the structure and function of this
      multitransmembrane protein in the brain. Using a panel of region-specific PS
      antibodies, we characterized the presenilin polypeptides in mammalian tissues,
      including brains of normal, AD, and PS1-linked FAD subjects, and in transfected
      and nontransfected cell lines. Very little full-length PS1 or -2 was detected in
      brain and untransfected cells; instead the protein occurred as a heterogeneous
      array of stable N- and C-terminal proteolytic fragments that differed subtly
      among cell types and mammalian tissues. Sequencing of the major C-terminal
      fragment from PS1-transfected human 293 cells showed that the principal
      endoproteolytic cleavage occurs at and near Met298 in the proximal portion of the
      large hydrophilic loop. Full-length PS1 in these cells is quickly turned over
      (T1/2 approximately 60 min), in part to the two major fragments. The sizes and
      amounts of the PS fragments were not significantly altered in four FAD brains
      with the Cys410Tyr PS1 missense mutation. Our results indicate that presenilins
      are rapidly processed to N- and C-terminal fragments in both neural and nonneural
      cells and that interference with this processing is not an obligatory feature of
      FAD-causing mutations.

PMID- 9173930
TI  - Identification of candidate proteins binding to prion protein.
AB  - Prion diseases are disorders of protein conformation that produce
      neurodegeneration in humans and animals. Studies of transgenic (Tg) mice indicate
      that a factor designated protein X is involved in the conversion of the normal
      cellular prion protein (PrPC) into the scrapie isoform (PrPSc); protein X appears
      to interact with PrPC but not with PrPSc. To search for PrPC binding proteins, we
      fused PrP with alkaline phosphatase (AP) to produce a soluble, secreted probe.
      PrP-AP was used to screen a lambdagt11 mouse brain cDNA library, and six clones
      were isolated. Four cDNAs are novel while two clones are fragments of Nrf2 (NF-E2
      related factor 2) transcription factor and Aplp1 (amyloid precursor-like protein
      1). The observation that PrP binds to a member of the APP (amyloid precursor
      protein) gene family is intriguing, in light of possible relevance to Alzheimer's
      disease. Four of the isolated clones are expressed preferentially in the mouse
      brain and encode a similar motif.

PMID- 9173931
TI  - "A finite-element model of oxygen diffusion in the pulmonary capillaries".

PMID- 9173932
TI  - Augmentation of exercise-induced muscle sympathetic nerve activity during muscle
      heating.
AB  - The muscle metabo- and mechanoreflexes have been shown to increase muscle
      sympathetic nerve activity (MSNA) during exercise. Group III and IV muscle
      afferents, which are believed to mediate this response, have been shown to be
      thermosensitive in animals. The purpose of the present study was to evaluate the
      effect of muscle temperature on MSNA responses during exercise. Eleven subjects
      performed ischemic isometric handgrip at 30% of maximal voluntary contraction to
      fatigue, followed by 2 min of postexercise muscle ischemia (PEMI), with and
      without local heating of the forearm. Local heating of the forearm increased
      forearm muscle temperature from 34.4 +/- 0.2 to 38.9 +/- 0.3 degree C (P =
      0.001). Diastolic and mean arterial pressures were augmented during exercise in
      the heat. MSNA responses were greater during ischemic handgrip with local heating
      compared with control (no heating) after the first 30 s. MSNA responses at
      fatigue were greater during local heating. MSNA increased by 16 +/- 2 and 20 +/-
      2 bursts per 30 s for control and heating, respectively (P = 0.03). When
      expressed as a percent change in total activity (total burst amplitude), MSNA
      increased 531 +/- 159 and 941 +/- 237% for control and heating, respectively (P =
      0.001). However, MSNA was not different during PEMI between trials. This finding
      suggests that the augmentation of MSNA during exercise with heat was due to the
      stimulation of mechanically sensitive muscle afferents. These results suggest
      that heat sensitizes skeletal muscle afferents during muscle contraction in
      humans and may play a role in the regulation of MSNA during exercise.

PMID- 9173933
TI  - Changes in leg vein filling and emptying characteristics and leg volumes during
      long-term head-down bed rest.
AB  - Leg venous hemodynamics [venous distensibility index (VDI), arterial flow index
      (AFI), half-emptying time (T1/2)], and leg volumes (LV) were assessed by mercury
      strain-gauge plethysmography with venous occlusion and volometry, respectively,
      in seven men before, during, and after 42 days of 6 degrees head-down bed rest.
      Results showed a high increase in VDI up to day 26 of bed rest (+50% vs. control
      at day 26, P < 0.05), which tended to subside thereafter (+20% increase vs.
      control value at day 41, P < 0.05). VDI changes were associated with parallel
      changes in T1/2 (+54% vs. control at day 26 of bed rest, P < 0.05, and +25% vs.
      control at day 41, P < 0.05) and with a decrease in AFI (-49% at day 41 vs. P <
      0.05). LV continuously decreased throughout bed rest (-13% vs. control at day 41,
      P < 0.05) but was correlated with VDI only during the first month of bed rest.
      These results show that during long-term 6 degrees head-down bed rest alterations
      of leg venous compliance are associated with impairment of venous emptying
      capacities and arterial flow. Changes in skeletal muscle mass and fluid shifts
      may account for venous changes during the first month of bed rest but,
      subsequently, other physiological factors, to be determined, may also be involved
      in leg venous hemodynamic alterations.

PMID- 9173934
TI  - Otolithic and tonic neck receptors control of limb blood flow in humans.
AB  - The aim of this study was to evaluate the role of otolithic receptors and neck
      mechanoreceptors on the control of the cardiovascular system. We measured calf
      (CBF) and forearm blood flow (FBF) by strain-gauge plethysmography, mean arterial
      pressure (MAP), and heart rate (HR) in 12 healthy subjects in two body positions
      (lying prone and on the left side) and three head positions (reference, flexion,
      and extension). When the subjects were lying prone, CBF and FBF were lower in
      head flexion (5.2 +/- 0.6 and 3.2 +/- 0.4 ml.min-1.100 ml-1, respectively) than
      in reference position (5.8 +/- 0.4 and 3.8 +/- 0.3 ml.min-1.100 ml-1; P < 0.05),
      with no significant difference in MAP and HR. When the subjects were lying on the
      side, changing the head position from reference to flexion significantly
      increased FBF (from 3.7 +/- 0.2 to 4.2 +/- 0.4 ml.min-1. 100 ml-1), MAP (from
      97.2 +/- 3.3 to 102.4 +/- 5.8 mmHg), and HR (from 63.7 +/- 1.4 to 65.9 +/- 2.5
      beats/min; P < 0.05). Because otolithic receptors and neck mechanoreceptors are
      involved when the subjects are lying prone, and otolithic receptors are not
      involved when the subjects are lying on the side, the results suggest that
      otolithic and neck mechanoreceptors exert significant influences over the
      cardiovascular system.

PMID- 9173935
TI  - Increase in percutaneous muscle biopsy yield with a suction-enhancement
      technique.
AB  - The percutaneous muscle biopsy technique is used in clinical practice and
      biomedical research. We developed a new enhanced-suction technique [suction
      enhancing nipples (SEN)] and compared it with techniques currently in practice by
      assessing biopsy yields on anesthetized pigs. We applied the enhanced-suction
      technique to human subjects participating in a clinical trial. In the pig, there
      was a mean 91% (1.9-fold) increase in the size of the samples obtained with the 4
      mm needle when SEN was used and a mean 507% (fivefold) increase in sample size
      when the SEN was applied to the 6-mm needles. Nine passes of the 6-mm needle with
      SEN obtained from five consecutive human subjects yielded a mean individual
      sample size of 109.4 mg or 219.4 mg per needle pass when using the double-sample
      technique. Adequate tissue samples for histomorphometric and other analyses were
      obtained in all samples obtained. The percutaneous muscle biopsy performed with
      enhanced suction using inexpensive, readily available nipples enhances tissue
      yield two- to fivefold.

PMID- 9173936
TI  - Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation
      in rabbits.
AB  - Acid-induced lung injury is mediated primarily by activated neutrophils. Although
      a prior study demonstrated that acid-induced neutrophil influx into the air
      spaces was not CD18 dependent, we hypothesized that either a neutralizing anti
      CD18 monoclonal antibody (MHM23) or a neutrophil inhibitory factor (NIF), NIF
      (CD11b,18), might attenuate acid-induced lung injury in rabbits by interfering
      with neutrophil activation. This hypothesis derived from in vitro stu ies that
      reported that anti-CD18 therapy prevented tumor necrosis factor-alpha-induced
      neutrophil activation. Hydrochloric acid (pH = 1.5 in one-third normal saline) or
      one-third normal saline (4 ml/kg) was instilled into the lungs of ventilated,
      anesthetized rabbits. The rabbits were studied for 6 h. In acid-instilled rabbits
      without the anti-CD18 monoclonal antibody or NIF (CD11b,18), severe lung injury
      developed. In acid-instilled rabbits, pretreatment (5 min before acid) with the
      anti-CD18 monoclonal antibody (2 mg/kg i.v.) or pretreatment with the NIF (anti
      CD11b,18, 10 mg/kg i.v.) prevented 50-70% of acid-induced abnormalities in
      oxygenation, the increase in extravascular lung water, and extravascular protein
      accumulation. The anti-CD18 monoclonal antibody was associated with a significant
      increase in air space neutrophils by bronchoalveolar lavage, suggesting that the
      neutrophils respond normally to chemotactic stimuli but that the neutrophils did
      not injure the lung even though they accumulated in the air spaces. In summary,
      neutralization of CD18 attenuates the acute lung injury after acid instillation
      without reducing the number of neutrophils in the air spaces, suggesting that
      anti-CD18 therapy may be beneficial because of its capacity to reduce neutrophil
      activation.

PMID- 9173937
TI  - Weight loss and wrestling training: effects on nutrition, growth, maturation,
      body composition, and strength.
AB  - Adolescent wrestlers (n = 9, 15.4 yr) and recreationally active control
      adolescent males (n = 7, 15.7 yr) were measured before, at the end (late season),
      and 3.5-4 mo after a wrestling season to assess the influence of dietary
      restriction on growth, maturation, body composition, protein nutrition, and
      muscular strength. Controls consumed adequate amounts of energy, carbohydrate
      (CHO), protein, and fat, and demonstrated normal gains in weight, fat mass (FM)
      and fat-free mass (FFM). Wrestlers consumed a high-CHO (61 +/- 2% kcal), low-fat
      (24 +/- 2% kcal) diet during the season but did not consume adequate energy (24.7
      +/- 3.5 kcal.kg-1.day-1) or protein (0.9 g.kg-1.day-1). Deficient dietary intake
      reduced prealbumin levels (26.0 +/- 1.9 vs. 20.2 +/- 0.9 mg/dl) and slowed the
      accrual of lean arm and thigh cross-sectional muscle areas (AXSECT, TXSECT,
      respectively). For wrestlers, dietary deficiency also decreased weight (60.3 +/-
      3.5 to 58.0 +/- 3.3 kg), relative fat (9.9 +/- 0.5 to 8.0 +/- 0.7%), and FM (6.0
      +/- 0.5 to 4.7 +/- 0.6 kg). Postseason, wrestlers and controls consumed similar
      diets, and wrestlers had significant increases in prealbumin, AXSECT, and TXSECT.
      Wrestlers also increased their weight (6.1 +/- 0.6 kg), FFM (3.0 +/- 0.6 kg), and
      FM (3.2 +/- 0.5 kg) postseason. Rates of bone maturation and segmental growth
      were not different between the groups. The wrestlers had reductions in elbow and
      knee strength from preseason to late season but increases postseason. Lean tissue
      changes were associated with the changes in strength and power (r = 0.72-0.91, P
      < 0.001). After covariance for FFM or limb-specific cross section, few
      significant changes remained. In conclusion, dietary restriction reduced protein
      nutrition and muscular performance but produced little effect on linear growth
      and maturation. Prealbumin levels and the rate of lean tissue accrual were
      positively related (r = 0.43, P < or = 0.05).

PMID- 9173938
TI  - Weight loss and wrestling training: effects on growth-related hormones.
AB  - Adolescent wrestlers (n = 9, 15.4 yr) and recreationally active control males (n
      = 7, 15.7 yr) were measured before, at the end of, and 3.5-4 mo after a
      competitive wrestling season to assess the influence of dietary restriction on
      growth-related hormones. Wrestlers had significant elevations preseason to late
      season for morning serum concentrations (mean of 8 serial samples) of growth
      hormone (GH; 2.9 +/- 0.7 vs. 6.5 +/- 1.4 ng/ml) and sex hormone-binding globulin
      (SHBG; 16.1 +/- 2.3 vs. 27.9 +/- 6.9 nmol/l) and significant reductions in GH
      binding protein (GHBP; 178 +/- 19 vs. 109 +/- 17 pmol/l), insulin-like growth
      factor I (IGF-I; 332 +/- 30 vs. 267 +/- 34 ng/ml), testosterone (T; 4.9 +/- 0.4
      vs. 3.6 +/- 0.4 ng/ml), and free testosterone (Free-T; 22.4 +/- 3.6 vs. 15.7 +/-
      2.8 pg/ml). Wrestlers had significant postseason reductions in GH (3.44 +/- 1.30
      ng/ml) and SHBG (10.43 +/- 4.13 nmol/l) but elevations in GHBP (66.7 +/- 23.8
      pmol/l), IGF-I (72.9 +/- 25.1 ng/ml), T (2.10 +/- 0.46 ng/ml), and Free-T (9.76
      +/- 3.01 pg/ml). Concentrations of luteinizing hormone (LH), estradiol,
      prolactin, cortisol, insulin, and thyroid hormones did not differ because of
      exercise-dietary practices of wrestlers. In-season elevations in GH, with
      concomitant reductions in GHBP and IGF-I, that were reversed during the
      postseason suggest a reduction in GH receptor number and partial GH resistance
      during the season. Nonelevated LH with reduced T levels suggests a central
      hypothalamic-pituitary-gonadal (H-P-G) axis impairment. In conclusion,
      undernutrition may lead to altered H-P-G and GH-IGF-I axes function in adolescent
      wrestlers. However, only the wrestlers' late-season Free-T concentrations were
      outside the normal range, and the hormone axis impairments were quickly reversed.
      The present data do not address hormonal axis responses to several years of
      wrestling and weight loss.

PMID- 9173939
TI  - Fibrinolytic responses to acute physical activity in older hypertensive men.
AB  - We tested the hypothesis that the fibrinolytic response to acute physical
      activity is impaired in sedentary older hypertensive men, which may contribute to
      the risk of exertion-triggered acute myocardial infarction in this population.
      Tissue-type plasminogen activator (t-PA) antigen and activity and plasminogen
      activator inhibitor-1 (PAI-1) antigen and activity were measured in 12
      hypertensive (69 +/- 1 yr) and 11 normotensive (64 +/- 1 yr) men before and after
      an acute bout of submaximal exercise. Contrary to our hypothesis, there were no
      differences between the two groups in the fibrinolytic response to exercise. t-PA
      antigen and activity were significantly elevated in both the hypertensive (38 and
      172%, respectively) and normotensive (45 and 130%, respectively) groups
      immediately after exercise but they returned to resting levels within 30 min.
      There was no change in PAI-1 antigen levels immediately after exercise in either
      group; however, PAI-1 antigen was significantly lower at 30 and 60 min
      postexercise in both the hypertensive (31 and 16%, respectively) and normotensive
      (35 and 20%, respectively) groups. PAI-1 activity was significantly lower
      immediately after exercise in both the hypertensive (25%) and normotensive (22%)
      groups and remained lower than preexercise levels at 30 min (23 and 26%,
      respectively) and 60 min (16 and 12%, respectively) postexercise in both groups.
      The results of this study demonstrate that the fibrinolytic response to an acute
      bout of moderate physical activity is not impaired in sedentary older
      hypertensive men.

PMID- 9173940
TI  - cAMP production in rabbit carotid body: role of adenosine.
AB  - In the present study, we have investigated the possible role of adenosine in the
      hypoxia-mediated increase in adenosine 3',5'-cyclic monophosphate (cAMP) in the
      carotid body. cAMP levels in rabbit carotid bodies superfused in vitro for 10 min
      were increased in the presence of adenosine (100 microM and 1.0 mM; maximum
      increase = 127%, P < 0.01). These effects were reduced by the nonspecific
      adenosine-receptor antagonist 1,3-dipropyl-8[p-sulfophenyl]xanthine (DPSPX; 10
      microM). The specific A2-receptor agonist 2-[4'(2-carboxymethyl)phenylethylamino]
      5'-N-ethylcarboxamido adenosine (CGS-21680; 100 nM) also elevated carotid body
      cAMP levels, an effect that was blocked by the specific A2-antagonist 3,7
      dimethyl-L-propargyl-xanthine (DMPX; 50 microM). Hypoxia-evoked elevations in
      cAMP were potentiated in the presence of the adenosine-uptake inhibitor
      dipyridamole (100 nM) and blocked by exposure to adenosine-receptor antagonists.
      Our data suggest that the rabbit carotid body contains specific adenosine
      receptors (A2 subtype) that are positively coupled to adenylate cyclase and that
      increases in cAMP associated with hypoxia are mediated by the release of
      endogenous adenosine.

PMID- 9173941
TI  - Selective endothelial dysfunction in conscious dogs after cardiopulmonary bypass.
AB  - It has previously been demonstrated that cardiopulmonary bypass (CPB) causes
      prolonged pulmonary vascular hyperreactivity (D.P. Nyhan, J.M. Redmond, A.M.
      Gillinov, K. Nishiwaki, and P.A. Murray. J. Appl. Physiol. 77: 1584-1590, 1994).
      This study investigated the effects of CPB on endothelium-dependent
      (acetylcholine and bradykinin) and endothelium-independent (sodium nitroprusside)
      pulmonary vasodilation in conscious dogs. Continuous left pulmonary vascular
      pressure-flow (LP-Q) plots were generated in conscious dogs before CPB and again
      in the same animals 3-4 days post-CPB. The dose of U-46619 used to acutely
      preconstrict the pulmonary circulation to similar levels pre- and post-CPB was
      decreased (0.13 +/- 0.01 vs. 0.10 +/- 0.01 mg.kg-1.min-1, P < 0.01) after CPB.
      Acetylcholine, bradykinin, and sodium nitroprusside all caused dose-dependent
      pulmonary vasodilation pre-CPB. The pulmonary vasodilator response to
      acetylcholine was completely abolished post-CPB. For example, at left pulmonary
      blood flow of 80 ml.kg-1.min-1 acetylcholine (10 micrograms.kg-1.min-1) resulted
      in 72 +/- 15% reversal (P < 0.01) of U-46619 preconstriction pre-CPB but caused
      no change post-CPB. However, the responses to bradykinin and sodium nitroprusside
      were unchanged post-CPB. The impaired pulmonary vasodilator response to
      acetylcholine, but not to bradykinin, suggests a selective endothelial defect
      post-CPB. The normal response to sodium nitroprusside indicates that cGMP
      mediated vasodilation is unchanged post-CPB.

PMID- 9173942
TI  - Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in
      humans.
AB  - Our aim was to determine whether sympathetic withdrawal alone can account for the
      profound forearm vasodilation that occurs during syncope in humans. We also
      determined whether either vasodilating beta 2-adrenergic receptor or nitric oxide
      (NO) contributes to this dilation. Forearm blood flow was measured bilaterally in
      healthy volunteers (n = 10) by using plethysmography during two bouts of graded
      lower body negative pressure (LBNP) to syncope. In one forearm, drugs were
      infused via a brachial artery catheter while the other forearm served as a
      control. In the control arm, forearm vascular resistance (FVR) increased from 77
      +/- 7 units at baseline to 191 +/- 36 units with -40 mmHg of LBNP (P < 0.05).
      Mean arterial pressure fell from 94 +/- 2 to 47 +/- 4 mmHg just before syncope,
      and all subjects demonstrated sudden bradycardia at the time of syncope. At the
      onset of syncope, there was sudden vasodilation and FVR fell to 26 +/- 6 units (P
      < 0.05 vs. baseline). When the experimental forearm was treated with bretylium,
      phentolamine, and propranolol, baseline FVR fell to 26 +/- 2 units, the
      vasoconstriction during LBNP was absent, and FVR fell further to 16 +/- 1 units
      at syncope (P < 0.05 vs. baseline). During the second trial of LBNP, mean
      arterial pressure again fell to 47 +/- 4 mmHg and bradycardia was again observed.
      Treatment of the experimental forearm with the NO synthase inhibitor NG
      monomethyl-L-arginine in addition to bretylium, phentolamine, and propranolol
      significantly increased baseline FVR to 65 +/- 5 units but did not prevent the
      marked forearm vasodilation during syncope (FVR = 24 +/- 4 vs. 29 +/- 8 units in
      the control forearm). These data suggest that the profound vasodilation observed
      in the human forearm during syncope is not mediated solely by sympathetic
      withdrawal and also suggest that neither beta 2-adrenergic-receptor-mediated
      vasodilation nor NO is essential to observe this response.

PMID- 9173943
TI  - Tone-entropy analysis on cardiac recovery after dynamic exercise.
AB  - Autonomic controls on heart rate variability have been investigated; however,
      sympathovagal interactive modulations remain unexplored. The purpose of this
      study is to present a new method, tone-entropy analysis (T-E analysis) of heart
      period fluctuations, and to make clear an intensive cooperation of autonomic
      networks in heart recovery. On the basis of evidence obtained in animal
      experiments, we hypothesized that heart periods are lengthened or shortened beat
      to beat by assumed physiological mediators: accelerator and inhibitor. Their
      operations were evaluated through a normalized successive variation of the
      period, that is, the percentage index (PI). The process was described through PI
      distributions by using two indexes, tone and entropy, standard values of which
      were obtained through pharmacological autonomic blockade experiment. T-E analysis
      was applied to heart recovery (70 min) after dynamic exercise by 12 female
      athletes. Interactive autonomic modulations were expressed by a curved path in
      tone-entropy space. Results suggested that heart rate decay proceeds not by
      withdrawal of one pathway but by increasing activity of both pathways as
      vagosympathetic balance inclines slightly but significantly to the vagus division
      in the course of recovery. The process was examined through Fourier spectral
      analysis as well.

PMID- 9173944
TI  - Gender-specific regional changes in genetic structure of muscularity in early
      adolescence.
AB  - Genetic and environmental influences on muscle circumference measurements of the
      extremities were estimated in 105 pairs of twins between 10 and 14 yr of age.
      Four circumferences, extended upper arm (EAC), forearm (FC), thigh (TC), and calf
      (CC), were measured. Univariate model fitting revealed that the largest part (87
      95%) of the variance for all circumferences at most ages was explained by
      additive genetic factors. Sex differences were observed for some age categories.
      Multivariate analyses showed a different pattern evolving according to age and
      gender. In boys from 10 to 12 yr of age, one general genetic factor influenced
      all four circumferences. With increasing age, an arm-leg model emerged, one
      genetic factor influencing the arm and another genetic factor the leg
      circumferences. In young girls one genetic factor loaded on the proximal (EAC,
      TC) and another on the distal (FC, CC) circumferences. With subjects at age 14
      yr, an arm-leg model was observed. High genetic correlations indicated that
      genetic factors related to EAC, FC, TC, and CC did not act independently. The age
      and gender-specific changes in the genetic structure suggest pubertal influences.
      This study shows that muscle circumferences are highly heritable characteristics
      and are therefore a promising starting point at which to locate their genes. Gene
      mapping could validate the gender-specific change of the genetic structure with
      age and region.

PMID- 9173945
TI  - Responses of group III and IV muscle afferents to dynamic exercise.
AB  - Tetanic contraction of hindlimb skeletal muscle, induced by electrical
      stimulation of either ventral roots or peripheral nerves, is well known to
      activate group III and IV afferents. Nevertheless, the effect of dynamic exercise
      on the discharge of these thin fiber afferents is unknown. To shed some light on
      this question, we recorded in decerebrate cats the discharge of 24 group III and
      10 group IV afferents while the mesencephalic locomotor region (MLR) was
      stimulated electrically. Each of the 34 afferents had their receptive fields in
      the triceps surae muscles. Stimulation of the MLR for 1 min caused the triceps
      surae muscles to contract rhythmically, an effect induced by an alpha-motoneuron
      discharge pattern and recruitment order almost identical to that occurring during
      dynamic exercise. Eighteen of the 24 group III and 8 of the 10 group IV muscle
      afferents were stimulated by MLR stimulation. The oxygen consumption of the
      dynamically exercising triceps surae muscles was increased by 2.5-fold over their
      resting levels. We conclude that low levels of dynamic exercise stimulate group
      III and IV muscle afferents.

PMID- 9173946
TI  - Muscle chemoreflex increases renal sympathetic nerve activity during exercise.
AB  - Activation of the muscle chemoreflex increases sympathetic drive to skeletal
      muscle in humans. This study investigated whether activation of the muscle
      chemoreflex augments the renal sympathetic nerve activity (RSNA) response to
      dynamic exercise in rabbits. The muscle chemoreflex was evoked by hindlimb
      ischemia during exercise on a motorized treadmill. Seven New Zealand White
      rabbits performed a nonischemic control protocol and a hindlimb ischemia protocol
      in which terminal aortic blood flow (Qta) was reduced to 51 +/- 2% of
      preocclusion Qta by partial aortic occlusion after 1.5 min of exercise. Mean
      arterial pressure (MAP), heart rate, RSNA and Qta increased in response to
      exercise and were similar between trials during the first 1.5 min of exercise. In
      the control trial, Qta, MAP, and RSNA were stable at an elevated level through an
      additional 3.5 min of exercise. Hindlimb ischemia produced a potent pressor
      response that plateaued after 2.5 min (delta + 17 +/- 4 mmHg, where delta
      designates change). RSNA began to increase after 1.5 min of ischemic exercise and
      was significantly elevated relative to preocclusion RSNA at 2.5 (delta + 25 +/-
      9%) and 3.5 (delta + 47 +/- 12%) min of occlusion. These results suggest that the
      muscle chemoreflex can augment sympathoexcitatory drive to the kidney during
      dynamic exercise.

PMID- 9173947
TI  - Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit
      arterial segments.
AB  - Free hemoglobin (Hb) induces a potent vasoconstrictor response that may limit its
      therapeutic application as a red blood cell replacement. We have investigated
      whether encapsulation of stroma-free Hb (SFHb) or cross-linked Hb (alpha alpha
      Hb) in liposomes modulates Hb vasoactivity in isolated blood vessels. Relaxation
      of rabbit thoracic vessels was measured before and after exposure to acellular
      SFHb, alpha alpha-Hb, and liposome-encapsulated SFHb or alpha alpha-Hb. SFHb and
      alpha alpha-Hb caused significant inhibition of carbachol-induced relaxation at
      0.5 mg/dl, whereas encapsulation inhibited vessel relaxation at 30- to 60-fold
      higher Hb concentrations. The contractile response of rabbit ear arterial
      segments to electrical stimulation in the presence of acellular alpha alpha-Hb
      resulted in a 150% increase (EC150) in contractile amplitude at 0.23 mg/dl,
      whereas the EC150 for encapsulated alpha alpha-Hb was 13.7 mg/dl. Mechanistic
      studies of the vasoconstrictor activity of Hb demonstrated that acellular alpha
      alpha-Hb had no effect on norepinephrine release in the rabbit ear artery. In
      addition, neither acellular nor encapsulated alpha alpha-Hb preparations
      inhibited endothelial nitric oxide (NO) synthase activity isolated from bovine
      pulmonary artery. However, inhibition of vessel relaxation by acellular or
      encapsulated alpha alpha-Hb was reversed by the NO donor S-nitrosylpenacillamine,
      implicating Hb-NO binding as a possible mechanism for the vasoconstrictor
      response. In vitro stopped-flow kinetic studies of Hb-NO binding showed similar
      rates of reaction for conversion of oxyhemoglobin to methemoglobin (metHb; < 2
      ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular
      and encapsulated alpha alpha-Hb, demonstrating that liposome encapsulation does
      not retard NO-Hb binding. The attenuated vasoactivity of encapsulated Hb may,
      therefore, result from the limited access of encapsulated Hb to NO imposed by the
      physical size of the liposome and reduced penetration of Hb across the vascular
      endothelium.

PMID- 9173948
TI  - Effects of salbutamol on intracellular calcium oscillations in porcine airway
      smooth muscle.
AB  - Relaxation of airway smooth muscle (ASM) by beta-adrenoceptor agonists involves
      reduction of intracellular Ca2+ concentration ([Ca2+]i). In porcine ASM cells,
      acetylcholine induces [Ca2+]i oscillations that display frequency modulation by
      agonist concentration and basal [Ca2+]i. We used real-time confocal microscopy to
      examine the effect of salbutamol (1 nM to 1 microM), a beta 2-adrenoceptor
      agonist, on [Ca2+]i oscillations in freshly dissociated porcine ASM cells.
      Salbutamol decreased the frequency of [Ca2+]i oscillations in a concentration
      dependent fashion, completely inhibiting the oscillations at 1 microM. These
      effects were mimicked by a cell-permeant analog of adenosine 3',5'-cyclic
      monophosphate. The inhibitory effect of salbutamol was partially reversed by BAY
      K 8644. Salbutamol reduced [Ca2+]i even when sarcoplasmic reticulum (SR) Ca2+
      reuptake and Ca2+ influx were blocked. Lanthanum blockade of Ca2+ efflux
      attenuated the inhibitory effect of salbutamol on [Ca2+]i. The [Ca2+]i response
      to caffeine was unaffected by salbutamol. On the basis of these results, we
      conclude that beta 2-adrenoceptor agonists have little effect on SR Ca2+ release
      in ASM cells but reduce [Ca2+]i by inhibiting Ca2+ influx through voltage-gated
      channels and by enhancing Ca2+ efflux.

PMID- 9173949
TI  - A 33-yr follow-up of peak oxygen uptake and related variables of former physical
      education students.
AB  - In 1949, 27 female and 26 male physical education students were studied at a mean
      age of 22 and 25 yr, respectively. They were restudied in 1970 and 1982.
      Measurements included oxygen uptake, heart rate, and pulmonary ventilation during
      submaximal and maximal exercise on a cycle ergometer and treadmill. After 21 yr,
      peak aerobic power was significantly reduced, from 2.90 to 2.18 l/min and from
      4.09 to 3.28 l/min for women and men, respectively. After another 12 yr, the 1970
      maxima were not reduced further. From 1949 to 1982 there was a decrease in peak
      heart rate from 196 to 177 beats/min in women and from 190 to 175 beats/min in
      men (P < 0.05). Highest pulmonary ventilation did not change significantly. At an
      oxygen uptake of 1.5 l/min, the heart rate was the same in 1949 as in 1982. In
      conclusion, the physical fitness level of the subjects was well above average for
      these ages. From 1970 to 1982 there was no decline in the average peak aerobic
      power, a finding possibly related to increased habitual physical activity.

PMID- 9173950
TI  - Involvement of the fastigial nuclei in vagally mediated respiratory responses.
AB  - Previous studies have demonstrated that the cerebellum, especially the fastigial
      nucleus (FN), is capable of modulating respiratory responses to chemical and
      mechanical stimuli. Because there is evidence to show projections from vagal
      afferents to the FN, the goal of this study was to determine the role of the FN
      in the respiratory reflexes elicited by activation of vagal afferents.
      Experiments were performed in anesthetized (chloralose), paralyzed, and
      artificially ventilated cats with an occipital exposure of the cerebellum.
      Administration of capsaicin (Cap; 5-10 micrograms/kg) via the right external
      jugular vein at the end of inspiration and application of lung inflation (LI; 10
      cmH2O) during inspiration were carried out to stimulate nonmyelinated and
      myelinated vagal afferents, respectively. The phrenic neurogram was recorded as
      an index of the respiratory motor output. Control cardiorespiratory variables
      [expiratory duration (TE), arterial blood pressure] and their immediate responses
      to stimuli were compared before and after bilateral lesions of the FN. The
      results showed the following. 1) Cap injection and LI resulted in a dramatic
      increase in TE (apnea). 2) FN lesions did not significantly alter the control TE;
      however, the apneic duration induced by Cap injection was prolonged. 3) Neither
      FN lesions nor cerebellectomy affected the apneic duration that resulted from
      application of LI. 4) Cold blockade of the vagi (6-8 degrees C) eliminated the
      respiratory responses elicited by LI but not Cap injection; vagotomy abolished
      the responses to both stimuli. 5) FN lesions did not change the control ABP or
      its responses to either LI or Cap injection. It is concluded that the FN is
      involved in vagally mediated respiratory reflexes elicited by activation of
      nonmyelinated (C-fiber) vagal afferents.

PMID- 9173951
TI  - Skeletal muscle biochemical adaptations to exercise training in miniature swine.
AB  - The primary purpose of this study was to test the hypothesis that endurance
      exercise training induces increased oxidative capacity in porcine skeletal
      muscle. To test this hypothesis, female miniature swine were either trained by
      treadmill running 5 days/wk over 16-20 wk (Trn; n = 35) or pen confined (Sed; n =
      33). Myocardial hypertrophy, lower heart rates during submaximal stages of a
      maximal treadmill running test, and increased running time to exhaustion during
      that test were indicative of training efficacy. A variety of skeletal muscles
      were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3
      hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant
      enzymes. Fiber type composition of a representative muscle was also determined
      histochemically. The largest increase in CS activity (62%) was found in the
      gluteus maximus muscle (Sed, 14.7 +/- 1.1 mumol.min-1.g-1; Trn, 23.9 +/- 1.0; P <
      0.0005). Muscles exhibiting increased CS activity, however, were located
      primarily in the forelimb; ankle and knee extensor and respiratory muscles were
      unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA
      dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity
      was unchanged with training, as were activities of antioxidant enzymes.
      Histochemical analysis of the triceps brachii muscle (long head) revealed lower
      type IIB fiber numbers in Trn (Sed, 42 +/- 6%; Trn, 10 +/- 4; P < 0.01) and
      greater type IID/X fiber numbers (Sed, 11 +/- 2; Trn, 22 +/- 3; P < 0.025). These
      findings indicate that porcine skeletal muscle adapts to endurance exercise
      training in a manner similar to muscle of humans and other animal models, with
      increased oxidative capacity. Specific muscles exhibiting these adaptations,
      however, differ between the miniature swine and other species.

PMID- 9173952
TI  - Norepinephrine spillover at rest and during submaximal exercise in young and old
      subjects.
AB  - Aging is associated with elevations in plasma norepinephrine concentrations. The
      purpose of this investigation was to examine total body and regional
      norepinephrine spillover as an indicator of sympathetic nerve activity. Eight
      young (26 +/- 3 yr) and seven old (69 +/- 5 yr) male subjects were studied at
      rest and during 20 min of submaximal cycling exercise at 50% of peak work
      capacity. Norepinephrine spillover was determined by continuous intravenous
      infusion of [3H]norepinephrine. Arterial norepinephrine concentrations were
      significantly greater at rest for old vs. young subjects (280 +/- 36 vs. 196 +/-
      27 ng/ml, respectively). Whereas total norepinephrine spillover did not differ
      between groups at rest, hepatomesenteric norepinephrine spillover was 50% greater
      in old subjects compared with their young counterparts (51 +/- 7 vs. 34 +/- 5
      ng/min, respectively). Additionally, norepinephrine clearance rates at rest were
      significantly lower for the old subjects (-23%). During exercise, plasma
      norepinephrine concentrations increased compared with rest, with old subjects
      again demonstrating greater values than the young group. Hepatomesenteric
      norepinephrine spillover was significantly greater (+36%) during exercise for old
      subjects compared with young; however, no difference was found for whole body
      spillover rates between age groups. Norepinephrine clearance rates remained
      depressed (-80%) in the old subjects during exercise. Clearance of epinephrine
      mirrored that for norepinephrine both at rest and during exercise across age
      groups. It was concluded that in old subjects, a reduction in norepinephrine
      clearance and an increase in regional norepinephrine spillover can account for
      the higher plasma norepinephrine concentrations observed at rest. This
      relationship is not exacerbated by the stress imposed during an acute bout of
      exercise.

PMID- 9173953
TI  - Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats.
AB  - We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23
      mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and
      citrate synthase (CS) activities and GLUT-4 glucose transporter protein level,
      which are coregulated in many instances of altered neuromuscular activity, were
      analyzed in soleus (Sol), plantaris (PI), tibialis anterior (TA), extensor
      digitorum longus (EDL), and left ventricle. Protein content was significantly (P
      < 0.05) lower in all four hindlimb muscles after suspension compared with
      controls in both mature (21-44%) and old (17-43%) rats. Old rats exhibited
      significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK
      activities were significantly lower in the old rats for the Pl (19%) and TA
      (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL
      (24%) compared with the mature rats. Old age was also associated with a decrease
      in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS
      activities were lower in the Sol (20%) and EDL (18%) muscles from mature
      suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old
      suspended rats compared with corresponding controls. However, suspension was
      associated with significantly higher HK activities for all four hindlimb muscles
      examined, in both old (16-57%) and mature (10-43%) rats, and higher GLUT-4
      concentrations in the TA muscles of the old rats (68%) but not the mature rats.
      These results indicate that old age is associated with decreased CS and HK
      activities and GLUT-4 protein concentration for several rat hindlimb muscles, and
      these variables are not coregulated during suspension. Finally, old rat skeletal
      muscle appears to respond to suspension to a similar or greater degree than
      mature rat muscle responds.

PMID- 9173954
TI  - Effect of glucose supplement timing on protein metabolism after resistance
      training.
AB  - We determined the effect of the timing of glucose supplementation on fractional
      muscle protein synthetic rate (FSR), urinary urea excretion, and whole body and
      myofibrillar protein degradation after resistance exercise. Eight healthy men
      performed unilateral knee extensor exercise (8 sets/approximately 10
      repetitions/approximately 85% of 1 single maximal repetition). They received a
      carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl) immediately (t = 0 h) and
      1 h (t = +1 h) postexercise. FSR was determined for exercised (Ex) and control
      (Con) limbs by incremental L-[1-13C]leucine enrichment into the vastus lateralis
      over approximately 10 h postexercise. Insulin was greater (P < 0.01) at 0.5,
      0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater (P < 0.05) at 0.5 and
      0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex
      leg than in the CHO/Con leg (P = not significant) and 6.3% greater in the Pl/Ex
      leg than in the Pl/Con leg (P = not significant). 3-Methylhistidine excretion was
      lower in the CHO (110.43 +/- 3.62 mumol/g creatinine) than P1 condition (120.14
      +/- 5.82, P < 0.05) as was urinary urea nitrogen (8.60 +/- 0.66 vs. 12.28 +/-
      1.84 g/g creatinine, P < 0.05). This suggests that CHO supplementation (1 g/kg)
      immediately and 1 h after resistance exercise can decrease myofibrillar protein
      breakdown and urinary urea excretion, resulting in a more positive body protein
      balance.

PMID- 9173955
TI  - Venous and arterial reflex responses to positive-pressure breathing and lower
      body negative pressure.
AB  - We examined the relative importance of arteriolar and venous reflex responses
      during reductions in cardiac output provoked by conditions that increase
      [positive end-expiratory pressure (PEEP)] or decrease [lower body negative
      pressure (LBNP)] peripheral venous filling. Five healthy subjects were exposed to
      PEEP (10, 15, 20, and 25 cmH2O) and LBNP (-10, -15, -20, and -25 mmHg) to induce
      progressive but comparable reductions in right atrial transmural pressure
      (control to minimum): from 5.9 +/- 0.4 to 1.8 +/- 0.7 and from 6.5 +/- 0.6 to 2.0
      +/- 0.2 mmHg with PEEP and LBNP, respectively. Cardiac output (impedance
      cardiography) fell less during PEEP than during LBNP (from 3.64 +/- 0.21 to 2.81
      +/- 0.21 and from 3.39 +/- 0.21 to 2.14 +/- 0.24 l.min-1.m-2 with PEEP and LBNP,
      respectively), and mean arterial pressure increased. We observed sustained
      increases in forearm vascular resistance (i.e., forearm blood flow by venous
      occlusion plethysmography) and systemic vascular resistance that were greater
      during LBNP: from 19.7 +/- 2.91 to 27.97 +/- 5.46 and from 20.56 +/- 2.48 to
      50.25 +/- 5.86 mmHg.ml-1.100 ml tissue-1.min (P < 0.05) during PEEP and LBNP,
      respectively. Venomotor responses (venous pressure in the hemodynamically
      isolated limb) were always transient, significant only with the greatest
      reduction in right atrial transmural pressure, and were similar for LBNP and
      PEEP. Thus arteriolar rather than venous responses are predominant in blood
      volume mobilization from skin and muscle, and venoconstriction is not intensified
      with venous engorgement during PEEP.

PMID- 9173956
TI  - Recovery processes after repeated supramaximal exercise at the altitude of 4,350
      m.
AB  - We tested the hypothesis that prolonged exposure to high altitude would impair
      the restoration of muscle power during repeated sprints. Seven subjects performed
      two 20-s Wingate tests (WT1 and WT2) separated by 5 min of recovery, at sea level
      (N) and after 5-6 days at 4,350 m (H). Mean power output (MPO) and O2 deficit
      were measured during WT. O2 uptake (VO2) and ventilation (VE) were measured
      continuously. Blood velocity in the femoral artery (FBV) was recorded by Doppler
      ultrasound during recovery. Arterialized blood pH and concentrations of
      bicarbonate ([HCO3-]), venous plasma lactate ([La-]), norepinephrine ([NE]), and
      epinephrine ([Epi]) were measured before and after WT1 and WT2. MPO decreased
      between WT1 and WT2 by 6.9% in N (P < 0.05) and by 10.7% in H (P < 0.01). H did
      not further decrease MPO. O2 deficit decreased between WT1 and WT2 in H only (P <
      0.01). Peak VO2 after WT was reduced by 30-40% in H (P < 0.01), but excess
      postexercise O2 consumption was not significantly lowered in H. During recovery
      in H compared with N, VE, exercise-induced acidosis, and [NE] were higher, [Epi]
      tented to be higher, [La-] was not altered, and [HCO3-] and FBV were lower. The
      similar [La-] accumulation was associated with a higher exercise-induced acidosis
      and a larger increase in [NE] in H. We concluded from this study that prolonged
      exposure to high altitude did not significantly impair the restoration of muscle
      power during repeated sprints, despite a limitation of aerobic processes during
      early recovery.

PMID- 9173957
TI  - Effect of intermittent weight bearing on soleus fiber force-velocity-power and
      force-pCa relationships.
AB  - Rat permeabilized type I soleus fibers displayed a 33% reduction in peak power
      output and a 36% increase in the free Ca2+ concentration required for one-half
      maximal activation after 14 days of hindlimb non-weight bearing (NWB). We
      examined the effectiveness of intermittent weight bearing (IWB; consisting of
      four 10-min periods of weight bearing/day) as a countermeasure to these
      functional changes. At peak power output, type I fibers from NWB animals produced
      54% less force and shortened at a 56% greater velocity than did type I fibers
      from control weight-bearing animals while type I fibers from the IWB rats
      produced 26% more absolute force than did fibers from the NWB group and shortened
      at a velocity that was only 80% of the NWB group mean. As a result, no difference
      was observed in the average peak power of fibers from the IWB and NWB animals.
      Hill plot analysis of force-pCa relationships indicated that fibers from the IWB
      group required similar levels of free Ca2+ to reach half-maximal activation in
      comparison to fibers from the weight-bearing group. However, at forces < 50% of
      peak force, the force-pCa curve for fibers from the IWB animals clearly fell
      between the relationships observed for the other two groups. In summary, IWB
      treatments 1) attenuated the NWB-induced reduction in fiber Ca2+ sensitivity but
      2) failed to prevent the decline in peak power that occurs during NWB because of
      opposing effects on fiber force (an increase vs. NWB) and shortening velocity (a
      decrease vs. NWB).

PMID- 9173958
TI  - Improved fatigue resistance not associated with maximum oxygen consumption in
      creatine-depleted rats.
AB  - Effects of feeding of either creatine or its analog beta-guanidinopropionic acid
      (beta-GPA) on endurance work capacity and oxygen consumption were studied in
      rats. Resting high-energy phosphate contents in hindlimb muscles were lower in
      the beta-GPA group and higher in the creatine group than in controls. The
      glycogen contents in resting hindlimb muscles of rats fed beta-GPA were
      significantly higher than those in controls. The endurance run and swimming times
      to exhaustion were significantly greater (32-70%) in the beta-GPA group than in
      the control and creatine groups. However, there were no beneficial effects on the
      maximum oxygen consumption (VO2max) and oxygen transport capacity of blood by the
      feeding of beta-GPA. None of these parameters were significantly influenced by
      creatine supply. Both maximum exercise time and VO2max in the beta-GPA group were
      not changed by normalization of glycogen levels. The activities of mitochondrial
      enzymes in skeletal muscles were higher in the beta-GPA group than in the
      controls. Thus endurance capacity is improved if the respiratory capacity of
      muscles is increased, even when the contents of high-energy phosphates in muscles
      are lower. Increased endurance capacity was not directly associated with the
      elevated levels of muscle glycogen, oxygen transport capacity of blood, or
      VO2max.

PMID- 9173959
TI  - Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of
      alpha 1- and alpha 2-adrenoceptor activation.
AB  - The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery
      rings (150-300 microns in diameter) and the role of alpha 1- and alpha 2
      adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact
      arteries, NE increased tension in a dose-dependent manner, and the sensitivity
      for NE was further increased in the absence of endothelium. In intact but not in
      endothelium-denuded arteries, the response to NE was increased in the presence of
      both indomethacin (Indo; cyclooxygenase inhibitor) and NG-nitro-L-arginine methyl
      ester [L-NAME; nitric oxide (NO) synthase inhibitor], indicating that two
      endothelium-derived factors, NO and a prostanoid, modulate the NE-induced
      contraction. The alpha 1-AR antagonist prazosin shifted the NE dose-response
      curve to the right, and phenylephrine (alpha 1-AR agonist) induced a dose
      dependent contraction that was potentiated by L-NAME or removal of the
      endothelium. The sensitivity to NE was increased slightly by the alpha 2-AR
      antagonists yohimbine and idazoxan, and this effect was abolished by Indo or
      removal of the endothelium. Similarly, contractions induced by UK-14304 (alpha 2
      AR agonist) were potentiated by Indo or removal of the endothelium. These results
      suggest that NE-induced contraction is mediated through activation of alpha 1-
      and alpha 2-ARs on both smooth muscle and endothelium. Activation of the alpha 1-
      and alpha 2-ARs on the smooth muscle causes contraction, whereas activation of
      the endothelial alpha 1- and alpha 2-ARs induces relaxation through release of NO
      (alpha 1-ARs) and a prostanoid (alpha 2-ARs).

PMID- 9173960
TI  - Exercise-induced changes in beta-adrenergic-receptor mRNA level measured by
      competitive RT-PCR.
AB  - Competitive reverse transcription-polymerase chain reaction (RT-PCR) analysis was
      used to clarify whether dynamic exercise-induced increases in beta-adrenergic
      receptor (beta-AR) number in human lymphocytes are accompanied by increases in
      the beta-AR mRNA level. Sixteen healthy subjects performed cycle ergometry until
      exhaustion. Before and immediately after exercise, peripheral blood was drawn
      from a forearm vein for preparation of lymphocytes. Both the beta-AR mRNA level
      and the beta-AR number were significantly increased by exercise. The changes in
      beta-AR mRNA level and beta-AR number were significantly correlated (r = 0.63, P
      < 0.01). This finding suggests that a rapid increase in beta-AR mRNA level might
      be an early adaptive response of the sympathetic nervous system to dynamic
      exercise. In vitro incubation of lymphocytes with epinephrine had no effect on
      beta-AR mRNA levels, nor did adenosine 3',5'-cyclic monophosphate, protein kinase
      C, or intracellular Ca2+ increase the beta-AR mRNA level in vitro. Therefore, it
      appears that other mechanisms underlie the exercise-induced elevation of beta-AR
      mRNA levels in human lymphocytes.

PMID- 9173961
TI  - Augmented sympathetic tone alters muscle metabolism with exercise: lack of
      evidence for functional sympatholysis.
AB  - It is unclear whether sympathetic tone opposes dilator influences in exercising
      skeletal muscle. We examined high levels of sympathetic tone, evoked by lower
      body negative pressure (LBNP, -60 mmHg) on intramuscular pH and phosphocreatine
      (PCr) levels (31P-nuclear magnetic resonance spectroscopy) during graded rhythmic
      handgrip (30 contractions/min; approximately 17, 34, 52 and 69% maximal voluntary
      contraction). Exercise was performed with LBNP and without LBNP (Control). At the
      end of exercise, LBNP caused lower levels of muscle pH (6.59 +/- 0.09) compared
      with Control (6.78 +/- 0.05; P < 0.05). PCr recovery, an index of mitochondrial
      respiration, was less during the recovery phase of the LBNP trial. Exercise mean
      arterial pressure was not altered by LBNP. The protocols were repeated with
      measurements of forearm blood flow velocity and deep venous samples (active
      forearm) of hemoglobin (Hb) saturation, pH, and lactate. With LBNP, mean blood
      velocity was reduced at rest, during exercise, and during recovery compared with
      Control (P < 0.05). Also, venous Hb saturation and pH levels during exercise and
      recovery were lower with LBNP and lactate was higher compared with Control (P <
      0.05). We conclude that LBNP enhanced sympathetic tone and reduced oxygen
      transport. At high workloads, there was a greater reliance on nonoxidative
      metabolism. In other words, sympatholysis did not occur.

PMID- 9173962
TI  - Intravascular oxygen distribution in subcutaneous 9L tumors and radiation
      sensitivity.
AB  - Phosphorescence quenching was evaluated as a technique for measuring PO2 in
      tumors and for determining the effect of increased PO2 on sensitivity of the
      tumors to radiation. Suspensions of cultured 9L cells or small pieces of solid
      tumors from 9L cells were injected subcutaneously on the hindquarter of rats, and
      tumors were grown to between 0.2 and 1.0 cm in diameter. Oxygen-dependent
      quenching of the phosphorescence of intravenously injected Pd-meso-tetra-(4
      carboxyphenyl) porphine was used to image the in vivo distribution of PO2 in the
      vasculature of small tumors and surrounding tissue. Maps (512 x 480 pixels) of
      tissue oxygen distribution showed that the PO2 within 9L tumors was low (2-12
      Torr) relative to the surrounding muscle tissue (20-40 Torr). When the rats were
      given 100% oxygen or carbogen (95% O2-5% CO2) to breathe, the PO2 in the tumors
      increased significantly. This increase was variable among tumors and was greater
      with carbogen compared with 100% oxygen. Based on irradiation and regrowth
      studies, carbogen breathing increased the sensitivity of the tumors to radiation.
      This is consistent with the measured increase in PO2 in the tumor vasculature. It
      is concluded that phosphorescence quenching can be used for noninvasive
      determination of the oxygenation of tumors. This method for oxygen measurements
      has great potential for clinical application in tumor identification and therapy.

PMID- 9173963
TI  - Exercise-induced changes in circulating growth factors with cyclic variation in
      plasma estradiol in women.
AB  - The effect of 10 min of high-intensity cycling exercise on circulating growth
      hormone (GH), insulin-like growth factors I and II (IGF-I and -II), and insulin
      like growth factor binding protein 3 (IGF BP-3) was studied in nine eumenorrheic
      women (age 19-48 yr) at two different phases of the menstrual cycle. Tests were
      performed on separate mornings corresponding to the follicular phase and to the
      periovulatory phase of the menstrual cycle, during which plasma levels of
      endogenous estradiol (E2) were relatively low (272 +/- 59 pmol/l) and high (1,112
      +/- 407 pmol/l), respectively. GH increased significantly in response to exercise
      under both E2 conditions. Plasma GH before exercise (2.73 +/- 2.48 vs. 1.71 +/-
      2.09 micrograms/l) and total GH over 10 min of exercise and 1-h recovery (324 +/-
      199 vs. 197 +/- 163 ng) were both significantly greater for periovulatory phase
      than for follicular phase studies. IGF-I, but not IGF-II, increased acutely after
      exercise. IGF BP-3, assayed by radioimmunoassay, was not significantly different
      at preexercise, and exercise, or at 30-min recovery time points and was not
      different between the two study days. When assayed by Western blot, however,
      there was a significant increase in IGF BP-3 30 min after exercise for the
      periovulatory study. These findings indicate that the modulation of GH secretion
      associated with menstrual cycle variations in circulating E2 affects GH measured
      after exercise, at least in part, by an increase in baseline levels. The acute
      increase in IGF-I induced by exercise appears to be independent of the GH
      response and is not affected by menstrual cycle timing.

PMID- 9173964
TI  - Gas exchange and cardiovascular kinetics with different exercise protocols in
      heart transplant recipients.
AB  - Metabolic and cardiovascular adjustments to various submaximal exercises were
      evaluated in 82 heart transplant recipients (HTR) and in 35 control subjects (C).
      HTR were tested 21.5 +/- 25.3 (SD) mo (range 1.0-137.1 mo) posttransplantation.
      Three protocols were used: protocol A consisted of 5 min of rectangular 50-W load
      repeated twice, 5 min apart [5 min rest, 5 min 50 W (Ex 1), 5 min recovery, 5 min
      50 W (Ex 2)]; protocol B consisted of 5 min of rectangular load at 25, 50, or 75
      W; protocol C consisted of 15 min of rectangular load at 25 W. Breath-by-breath
      pulmonary ventilation (VE), O2 uptake (VO2), and CO2 output (VCO2) were
      determined. During protocol A, beat-by-beat cardiac output (Q) was estimated by
      impedance cardiography. The half times (t1/2) of the on- and off-kinetics of the
      variables were calculated. In all protocols, t1/2 values for VO2 on-, VE on-, and
      VCO2 on-kinetics were higher (i.e., the kinetics were slower) in HTR than in C,
      independently of workload and of the time post-transplantation. Also, t1/2 Q on-
      was higher in HTR than in C. In protocol A, no significant difference of t1/2 VO2
      on- was observed in HTR between Ex 1 (48 +/- 9 s) and Ex 2 (46 +/- 8 s), whereas
      t1/2 Q on- was higher during Ex 1 (55 +/- 24 s) than during Ex 2 (47 +/- 15 s).
      In all protocols and for all variables, the t1/2 off-values were higher in HTR
      than in C, In protocol C, no differences of steady-state VE, VO2, and VCO2 were
      observed in both groups between 5, 10, and 15 min of exercise. We conclude that
      1) in HTR, a "priming" exercise, while effective in speeding up the adjustment of
      convective O2 flow to muscle fibers during a second on-transition, did not affect
      the VO2 on-kinetics, suggesting that the slower VO2 on- in HTR was attributable
      to peripheral (muscular) factors; 2) the dissociation between Q on- and VO2 on
      kinetics in HTR indicates that an inertia of muscle metabolic machinery is the
      main factor dictating the VO2 on-kinetics; and 3) the VO2 off-kinetics was slower
      in HTR than in C, indicating a greater alactic O2 deficit in HTR and, therefore,
      a sluggish muscle VO2 adjustment.

PMID- 9173965
TI  - Evaluation of estimates of alveolar gas exchange by using a tidally ventilated
      nonhomogenous lung model.
AB  - The purpose of this study was to evaluate algorithms for estimating O2 and CO2
      transfer at the pulmonary capillaries by use of a nine-compartment tidally
      ventilated lung model that incorporated inhomogeneities in ventilation-to-volume
      and ventilation-to-perfusion ratios. Breath-to-breath O2 and CO2 exchange at the
      capillary level and at the mouth were simulated by using realistic cyclical
      breathing patterns to drive the model, derived from 40-min recordings in six
      resting subjects. The SD of the breath-by-breath gas exchange at the mouth around
      the value at the pulmonary capillaries was 59.7 +/- 25.5% for O2 and 22.3 +/-
      10.4% for CO2. Algorithms including corrections for changes in alveolar volume
      and for changes in alveolar gas composition improved the estimates of pulmonary
      exchange, reducing the SD to 20.8 +/- 10.4% for O2 and 15.2 +/- 5.8% for CO2. The
      remaining imprecision of the estimates arose almost entirely from using end-tidal
      measurements to estimate the breath-to-breath changes in end-expiratory alveolar
      gas concentration. The results led us to suggest an alternative method that does
      not use changes in end-tidal partial pressures as explicit estimates of the
      changes in alveolar gas concentration. The proposed method yielded significant
      improvements in estimation for the model data of this study.

PMID- 9173966
TI  - Anabolic influences of insulin-like growth factor I and/or growth hormone on the
      diaphragm of young rats.
AB  - It is controversial whether insulin-like growth factor I (IGF-I), growth hormone
      (GH), or their combination might enhance body growth and/or tissue anabolism in
      the well-fed animal with an intact somatotrophic axis. To assess this further, we
      studied four groups of adolescent rats: 1) control (Ctr), 2) GH, 3) IGF-I, and 4)
      GH/IGF-I. IGF-I was given via an osmotic minipump, whereas GH was injected
      subcutaneously for a period of 72 h. Diaphragm (Dia) contractile and fatigue
      properties were determined in vitro. Quantitative histochemical and morphometric
      analyses were performed on Dia fibers. Total serum IGF-I levels were
      significantly increased in the groups receiving growth factors. Although body
      weight increased to a greater extent in the animals receiving growth factors, a
      further synergistic effect was noted in the GH/IGF-I animals compared with either
      GH or IGF-I groups. Costal Dia mass was greater in the groups receiving growth
      factors. The Dia of GH/IGF-I animals was more fatigue resistant than the Dia in
      Ctr. The cross-sectional area of types IIa and IIx fibers were increased to a
      similar extent in all groups receiving growth factors compared with Ctr.
      Succinate dehydrogenase activity of type IIa fibers was significantly greater in
      the GH/IGF-I animals compared with the other groups. We conclude that the short
      term provision of growth factors to well-nourished, normally growing adolescent
      rats can accelerate body growth and promote selective hypertrophy of
      predominantly type II Dia fibers.

PMID- 9173967
TI  - Marked differences in functioning of the hypothalamic-pituitary-adrenal axis
      between groups of men.
AB  - To compare profiles of hypothalamic-pituitary-adrenal (HPA) responsiveness,
      healthy, moderately trained men (n = 15) were classified as high (n = 7) or low
      responders (n = 8) on the basis of plasma adrenocorticotropic hormone (ACTH)
      responses to strenuous treadmill exercise 4 h after 4 mg of dexamethasone (Dex).
      These groups were then evaluated to compare 1) HPA and growth hormone responses
      to exercise at 90% maximal oxygen uptake 4 h after placebo, Dex (4 mg), and
      hydrocortisone (100 mg); 2) pituitary-adrenal responses to infusion of arginine
      vasopressin (AVP); 3) plasma cortisol after a Dex suppression test (1 mg); and 4)
      behavioral characteristics. In comparison to low responders, high responders
      exhibited significantly 1) higher plasma ACTH responses to exercise after placebo
      and Dex; 2) higher plasma AVP secretion with exercise after placebo and marked
      Dex- and hydrocortisone-induced enhancement of exercise-induced AVP secretion; 3)
      lower Dex-induced increases in basal and stimulated growth hormone secretion; 4)
      higher plasma ACTH responses to infusion of AVP; and 5) a trend (P = 0.09) for
      higher trait anxiety ratings. Similar suppression of plasma cortisol was noted
      after 1 mg Dex. We conclude that subgroups of healthy male volunteers exhibit
      unique profiles of HPA responsiveness. We also believe that glucocorticoid
      pretreatment combined with strenuous exercise allows functional HPA
      responsiveness to be distinguished between subgroups of healthy controls and may
      be useful in the determination of susceptibility to disorders characterized by
      hyper- and hypo-HPA activation.

PMID- 9173968
TI  - Volume capacity and contraction control of the seal spleen.
AB  - Volume changes in the spleens of hooded seals (Cystophora cristata) and harp
      seals (Phoca groenlandica) were measured plethysmographically in vitro in
      response to epinephrine, norepinephrine, isoprenaline, phentolamine, and
      acetylcholine. Dilated spleens contracted forcefully within 1-3 min of alpha
      adrenoceptor activation with 1.0-5.0 micrograms epinephrine/kg body mass, whereas
      stimulation of beta-adrenoceptors and cholinergic receptors had little effect.
      The mass of dilated hooded seal spleens corresponded to 2-4% (n = 7) of body
      mass, with volume (V; ml) relating to body mass (M; kg) as follows: V = 12.0M +
      910 (r2 = 0.96, n = 4). Thus the spleen of a 250-kg hooded seal maximally expels
      3.9 liters, or 13%, of its estimated total blood volume. Average hematocrit in
      splenic venous outflow from dilated spleens was 90 +/- 3% (n = 3) in hooded seals
      and 85% (n = 2) in harp seals. From these data we have estimated that the aerobic
      diving limit of a 250-kg hooded seal increases only 105 s, at the most, if
      complete emptying of the spleen occurs during diving, while the corresponding
      estimate for a 112-kg harp seal is 80 s.

PMID- 9173969
TI  - Blood volume and cardiac index in rats after exchange transfusion with hemoglobin
      based oxygen carriers.
AB  - We have measured plasma volume and cardiac index in rats after 50% isovolemic
      exchange transfusion with human hemoglobin cross-linked between the alpha-chains
      with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) and with bovine hemoglobin
      modified with polyethylene glycol (PEGHb). alpha alpha Hb and PEGHb differ in
      colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity
      (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr,
      respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight
      (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye
      dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb
      treated animals were significantly elevated (74.0 +/- 3.5 ml/kg) compared with
      animals treated with alpha alpha Hb (49.0 +/- 1.2 ml/kg) or Ringer lactate (48.0
      +/- 2.0 ml/kg) or with controls (58.2 +/- 1.9 ml/kg). Heart rate reduction after
      alpha alpha Hb exchange is opposite to that expected with blood volume
      contraction, suggesting that alpha alpha Hb may have a direct myocardial
      depressant action. The apparently slow elimination of PEGHb during the 2 h after
      its injection is a consequence of plasma volume expansion: when absolute
      hemoglobin (concentration x plasma volume) is compared for PEGHb and alpha alpha
      Hb, no difference in their elimination rates is found. These studies emphasize
      the need to understand blood volume regulation when the effects of cell-free
      hemoglobin on hemodynamic measurements are evaluated.

PMID- 9173970
TI  - Pathophysiology of neonatal lung injury induced by monoclonal antibody to
      surfactant protein B.
AB  - Near-term newborn rabbits were exposed via the airways to a monoclonal antibody
      to surfactant protein B and ventilated for 0-120 min. Control animals received
      nonspecific rabbit or mouse immunoglobulin G, saline, or no material via the
      airways. Administration of the antibody at > or = 40 mg/kg elicited an immediate,
      significant fall in lung-thorax compliance associated with progressive intra
      alveolar edema and/or alveolar collapse and necrosis and desquamation of airway
      epithelium, and hyaline membranes. The vascular-to-alveolar leak of human albumin
      and human immunoglobulin G, injected intravenously at birth and determined in
      lung lavage fluid 60-120 min after instillation of the antibody, was 1.8% for the
      left lung, with no difference between the markers. The average leak in control
      animals ventilated for 120 min was < 0.3% (P < 0.05). Cytospin preparations of
      lung lavage fluid from animals exposed to the antibody showed significantly
      increased recruitment of neutrophilic granulocytes. The pathology and
      pathophysiology of neonatal lung injury induced by the monoclonal antibody to
      surfactant protein B probably reflect a combination of direct inactivation of
      surfactant and an inflammatory response triggered by the immune reaction.

PMID- 9173971
TI  - Task failure with lack of diaphragm fatigue during inspiratory resistive loading
      in human subjects.
AB  - Task failure during inspiratory resistive loading is thought to be accompanied by
      substantial peripheral fatigue of the inspiratory muscles. Six healthy subjects
      performed eight resistive breathing trials with loads of 35, 50, 75 and 90% of
      maximal inspiratory pressure (MIP) with and without supplemental oxygen. MIP
      measured before, after, and at every minute during the trial increased slightly
      during the trials, even when corrected for lung volume (e.g., for 24 trials
      breathing air, 12.5% increase, P < 0.05). In some trials, task failure occurred
      before 20 min (end point of trial), and in these trials there was an increase in
      end-tidal PCO2 (P < 0.01), despite the absence of peripheral muscle fatigue. In
      four subjects (6 trials with task failure), there was no decline in twitch
      amplitude with bilateral phrenic stimulation or in voluntary activation of the
      diaphragm, even though end-tidal PCO2 rose by 1.6 +/- 0.9%. These results suggest
      that hypoventilation, CO2 retention, and ultimate task failure during resistive
      breathing are not simply dependent on impaired force-generating capacity of the
      diaphragm or impaired voluntary activation of the diaphragm.

PMID- 9173972
TI  - Effect of triiodothyronine augmentation on rat lung surfactant phospholipids
      during sepsis.
AB  - Surfactant functional effectiveness is dependent on phospholipid compositional
      integrity; sepsis decreases this through an undefined mechanism. Sepsis-induced
      hypothyroidism is commensurate and may be related. This study examines the effect
      of 3,3',5-triiodo-L-thyronine (T3) supplementation on surfactant composition and
      function during sepsis. Male Sprague-Dawley rats underwent sham laparotomy (Sham)
      or cecal ligation and puncture (CLP) with or without T3 supplementation [CLP/T3
      (3 ng/h)]. After 6, 12, or 24 h, surfactant was obtained by lavage. Function was
      assessed by a pulsating bubble surfactometer and in vivo compliance studies.
      Sepsis produced a decrease in surfactant phosphatidylglycerol and phosphatidic
      acid, with an increase in lesser surface-active lipids phosphatidylserine and
      phosphatidylinositol. Phosphatidylcholine content was not significantly changed.
      Sepsis caused an alteration in the fatty acid composition and an increase in
      saturation in most phospholipids. Hormonal replacement attenuated these changes.
      Lung compliance and surfactant adsorption were reduced by sepsis and maintained
      by T3 treatment. Thyroid hormone may have an active role in lung functional
      preservation through maintenance of surfactant homeostasis during sepsis.

PMID- 9173973
TI  - Thermal and circulatory responses during exercise: effects of hypohydration,
      dehydration, and water intake.
AB  - This investigation examined the distinct and interactive effects of initial
      hydration state, exercise-induced dehydration, and water rehydration in a hot
      environment. On four occasions, 10 men performed a 90-min heat stress test
      (treadmill walking at 5.6 km/h, 5% grade, 33 degrees C, 56% relative humidity).
      These heat stress tests differed in pretest hydration [2 euhydrated (EU) and 2
      hypohydrated (HY) trials] and water intake during exercise [2 water ad libitum
      (W) and 2 no water (NW) trials]. HY+NW indicated greater physiological strain
      than all other trials (P < 0.05-0.001) in heart rate, plasma osmolality (Posm),
      sweat sensitivity (g/degrees C.min), and rectal temperature. Unexpectedly, final
      HY+W and EU+W responses for rectal temperature, heart rate, and Posm were
      similar, despite the initial 3.9 +/- 0.2% hypohydration in HY+W. We concluded
      that differences in pretest Posm (295 +/- 7 and 287 +/- 5 mosmol/kg for HY+W and
      EU+W, respectively) resulted in greater water consumption (1.65 and 0.31 liter
      for HY+W and EU+W, respectively), no voluntary dehydration (0.9% body mass
      increase), and attenuated thermal and circulatory strain during HY+W.

PMID- 9173974
TI  - A finite-element model of oxygen diffusion in the pulmonary capillaries.
AB  - We determined the overall pulmonary diffusing capacity (DL) and the diffusing
      capacities of the alveolar membrane (Dm) and the red blood cell (RBC) segments
      (De) of the diffusional pathway for O2 by using a two-dimensional finite-element
      model developed to represent the sheet-flow characteristics of pulmonary
      capillaries. An axisymmetric model was also considered to assess the effect of
      geometric configuration. Results showed the membrane segment contributing the
      major resistance, with the RBC segment resistance increasing as O2 saturation
      (SO2) rises during the RBC transit: RBC contributed 7% of the total resistance at
      the capillary inlet (SO2 = 75%) and 30% toward the capillary end (SO2 = 95%) for
      a 45% hematocrit (Hct). Both Dm and DL increased as the Hct increased but began
      approaching a plateau near an Hct of 35%, due to competition between RBCs for O2
      influx. Both Dm and DL were found to be relatively insensitive (2-4%) to changes
      in plasma protein concentration (28-45%). Axisymmetric results showed similar
      trends for all Hct and protein concentrations but consistently overestimated the
      diffusing capacities (approximately 2.2 times), primarily because of an
      exaggerated air-tissue barrier surface area. The two-dimensional model correlated
      reasonably well with experimental data and can better represent the O2 uptake of
      the pulmonary capillary bed.

PMID- 9173975
TI  - Stabilized bubbles in the body: pressure-radius relationships and the limits to
      stabilization.
AB  - We previously outlined the fundamental principles that govern behavior of
      stabilized bubbles, such as the microbubbles being put forward as ultrasound
      contrast agents. Our present goals are to develop the idea that there are limits
      to the stabilization and to provide a conceptual framework for comparison of
      bubbles stabilized by different mechanisms. Gases diffuse in or out of stabilized
      bubbles in a limited and reversible manner in response to changes in the
      environment, but strong growth influences will cause the bubbles to cross a
      threshold into uncontrolled growth. Also, bubbles stabilized by mechanical
      structures will be destroyed if outside influences bring them below a critical
      small size. The in vivo behavior of different kinds of stabilized bubbles can be
      compared by using plots of bubble radius as a function of forces that affect
      diffusion of gases in or out of the bubble. The two ends of the plot are the
      limits for unstabilized growth and destruction; these and the curve's slope
      predict the bubble's practical usefulness for ultrasonic imaging or O2 carriage
      to tissues.

PMID- 9173977
TI  - Editorial

PMID- 9173976
TI  - The XPB subunit of repair/transcription factor TFIIH directly interacts with
      SUG1, a subunit of the 26S proteasome and putative transcription factor.
AB  - Mutations in the basal transcription initiation/DNA repair factor TFIIH are
      responsible for three human disorders: xeroderma pigmentosum (XP), cockayne
      syndrome (CS) and trichothiodystrophy (TTD). The non-repair features of CS and
      TTD are thought to be due to a partial inactivation of the transcription function
      of the complex. To search for proteins whose interaction with TFIIH subunits is
      disturbed by mutations in patients we used the yeast two-hybrid system and report
      the isolation of a novel XPB interacting protein, SUG1. The interaction was
      validated in vivo and in vitro in the following manner. (i) SUG1 interacts with
      XPB but not with the other core TFIIH subunits in the two-hybrid assay. (ii)
      Physical interaction is observed in a baculovirus co-expression system. (iii) In
      fibroblasts under non-overexpression conditions a portion of SUG1 is bound to the
      TFIIH holocomplex as deduced from co-purification, immunopurification and nickel
      chelate affinity chromatography using functional tagged TFIIH. Furthermore,
      overexpression of SUG1 in normal fibroblasts induced arrest of transcription and
      a chromatin collapse in vivo. Interestingly, the interaction was diminished with
      a mutant form of XPB, thus providing a potential link with the clinical features
      of XP-B patients. Since SUG1 is an integral component of the 26S proteasome and
      may be part of the mediator, our findings disclose a SUG1-dependent link between
      TFIIH and the cellular machinery involved in protein modelling/degradation.

PMID- 9173989
TI  - Cortical neurones exhibiting kainate-activated Co2+ uptake are selectively
      vulnerable to AMPA/kainate receptor-mediated toxicity.
AB  - Kainate-activated Co2+ uptake, a histochemical method that identifies cells
      bearing Ca2+-permeable AMPA/kainate receptors, labels approximately 15% of murine
      cortical neurones in cell culture. While exposure times exceeding several hours
      were needed for AMPA or kainate to destroy most cultured cortical neurones, the
      subpopulation exhibiting kainate-activated Co2+ uptake was selectively destroyed
      after AMPA or kainate exposures of only 10-60 min. No selective loss was seen
      after exposure to NMDA. Kainate toxicity on Co2+ uptake-positive neurones was
      dependent on extracellular Ca2+ concentration, and associated with an increase in
      intracellular free Ca2+ even in the absence of extracellular Na+. These results
      suggest that a distinct subpopulation of cortical neurones expresses AMPA/kainate
      receptors linked to Ca2+-permeable channels, and that this characteristic conveys
      enhanced vulnerability to kainate-induced, Ca2+-mediated, damage.

PMID- 9173990
TI  - Tardive dyskinetic syndrome in rats infected with Borna disease virus.
AB  - Tardive Dyskinesia (TD) is a hyperkinetic movement disorder caused by chronic
      treatment of psychiatric patients with dopamine (DA) receptor blocking drugs
      (Stacy & Jankovic 1991). Although TD is one of the most important and frequently
      encountered iatrogenic disorders in clinical medicine, its pathophysiology is
      poorly understood. We have observed a hyperkinetic movement disorder in rats
      experimentally infected with a neurotropic RNA virus, Borna disease virus, that
      may provide important insights into the pathophysiology of TD. Like TD patients,
      infected rats show prominent orofacial dyskinesias. In keeping with the dopamine
      (Goetz & Klawans 1982) and anatomic (Fibiger & Lloyd 1984) hypotheses of TD, the
      Borna disease rat model shows enhanced behavioural sensitivity to DA agonists and
      selective striatal cell damage. There is also evidence of DA deafferentation and
      heterogeneous reduction of D2 binding in the caudate-putamen, particularly from
      sites implicated in oral behaviour. These observations on a virus-induced
      movement disorder offer novel approaches to TD pathogenesis.

PMID- 9173991
TI  - Upregulation of NMDARI mRNA induced by MK-801 is associated with massive death of
      axotomized motor neurones in adult rats.
AB  - Studies on the pathogenesis of human motor neurone disease have suffered from the
      absence of models of motor neurone degeneration in adult animals. Normally in
      adult rodents, transection of motor neurone axons results in only a modest degree
      of neuronal death. We reasoned that axotomy-induced motor neurone death might be
      enhanced by modulating glutamatergic transmission. By axotomizing the facial
      nerve in adult rats and then administering MK-801 for the first week of a 4-week
      or 8-week post-lesion survival period, we induced a 67% motor neurone loss by 8
      weeks as compared with a 19% loss in controls. A possible explanation for the
      increased motor neurone loss after MK-801 treatment is that transient blockade of
      NMDA receptors may upregulate synthesis of NMDA receptor components. In order to
      test this idea, we employed quantitative in situ hybridization to determine the
      response of NMDAR1 mRNA to axotomy and axotomy + MK-801 treatment. Quantification
      of the percentage of area occupied by NMDAR1 silver grains per motor neurone
      somata indicated that axotomy alone did not provoke a change in NMDAR1 mRNA.
      However, axotomy and MK-801 combined treatment resulted in a highly significant
      upregulation of NMDAR1 mRNA when compared with controls or animals treated solely
      with axotomy. Our results suggest that motor neurone death in adult animals can
      be enhanced after axotomy in association with the upregulation of NMDA receptor
      mRNA. Thus, abnormalities in glutamate receptor signalling may lead to subacute
      motor neurone death in vivo. Furthermore these results indicate that transient
      treatment with MK-801 is a convenient method for enhancing the degree of motor
      neurone death after axotomy in adult animals.

PMID- 9173992
TI  - Evidence for formation of hydroxyl radicals during reperfusion after global
      cerebral ischaemia in rats using salicylate trapping and microdialysis.
AB  - Systemic administration of salicylate (SA) to rats (100 mg kg-1 i.p. ) was used
      as an in vivo trap of hydroxyl radicals (.OH). In the brain SA reacts with
      hydroxyl radicals to form the stable adducts 2, 3- and 2,5 dihydroxybenzoic acid
      (DHBAs) which can thus be taken as an index of .OH formation. The DHBAs were
      recovered by intracerebral microdialysis in hippocampus or striatum and
      quantified by high pressure liquid chromatography (HPLC) with electrochemical
      detection. There were no peaks corresponding to 2,5-DHBA or 2,3-DHBA in the
      chromatograms from rats not receiving SA. A basal level of 2,5-DHBA was seen in
      the dialysates from all animals given SA whereas 2, 3-DHBA was not detected. In
      one group of rats generation of free oxygen radicals was induced in the striatum
      by adding Fe2+ and ascorbate to the perfusion fluid to test the sensitivity of
      the system. Addition of Fe2+ ascorbate to the perfusion fluid induced a
      significant 7-fold increase in 2,5-DHBA that gradually returned to baseline after
      removal of Fe2+/ascorbate. In two other groups the microdialysis probes were
      implanted in either the striatum or the hippocampus and the animals were
      subjected to 20 min of four-vessel occlusion + hypotension (4-VOH). Significant
      reductions in 2,5-DHBA were detected during ischaemia followed by significant
      increases of 5-fold and 3-fold in the striatum and hippocampus, respectively,
      beginning immediately upon reperfusion and lasting for the remainder of the
      observation period (160 min).

PMID- 9173993
TI  - Beta-amyloid (beta/A4) deposition in the medial temporal lobe in Down's syndrome:
      effects of brain region and patient age.
AB  - The density of diffuse, primitive, classic and compact beta-amyloid (beta/A4)
      deposits was studied in the medial temporal lobe in 12 cases of Down's syndrome
      (DS) from 38 to 67 years of age. Total beta/A4 deposit density was greater in the
      adjacent cortex compared with regions of the hippocampus, and these differences
      were similar within each age group of patients. The ratio of the primitive to
      diffuse deposits was greater in the hippocampus than in the adjacent cortex.
      Total beta/A4 density did not vary significantly with patient age. However, the
      density of the diffuse deposits exhibited a parabolic, and the primitive, classic
      and compact deposits an inverted parabolic, response with age. Hence, in DS, (1)
      beta/A4 density remains relatively constant with age, (2) differences in beta/A4
      density between the hippocampus and adjacent cortex are established at an early
      age, and (3) mature beta/A4 subtype formation depends on brain region and patient
      age.

PMID- 9173994
TI  - TG-1: a marker for neuronal nuclei in Alzheimer's disease.
AB  - TG-1 is a monoclonal antibody (mAb) raised against paired helical filaments
      purified from Alzheimer's Disease (AD) brain by immunoaffinity chromatography. By
      immunocytochemistry, TG-1 reveals abundant staining of neuronal nuclei in AD
      brain, but little or no staining in normal brain. TG-1 stained nuclei are
      observed in areas of AD brain with neurofibrillary pathology and in certain
      neurones that are not normally affected. Biochemical studies with TG-1 show
      antigens of 32-38 kDa in pellets and 50 kDa in supernatants from brain, with no
      obvious differences between normal and AD. TG-1 also recognizes an unusual
      structure, i.e., a 'starburst' in brain tissue from AD and elderly normals.
      Starbursts are not immunoreactive for the astrocytic marker, glial fibrillary
      acidic protein, and are not associated with amyloid. Widespread nuclear staining
      is observed with TG-1 in rat brain, and the immunoreactive antigens in purified
      nuclei are similar to those in human brain. Thus, TG-1 identifies neuronal
      nuclear antigens that are altered in AD, and provides a new avenue for studying
      pathogenic mechanisms in the disease.

PMID- 9173995
TI  - Huntington's disease CAG trinucleotide repeats in pathologically confirmed post
      mortem brains.
AB  - CAG repeat expansion in the Huntington's disease gene (HD) was examined in
      postmortem brains from 310 clinically diagnosed and 15 'at risk' individuals.
      Presence of an expanded CAG allele (>37 units) was the cause of the disorder in
      almost all cases (307 of 310). Despite a diversity of reporting clinicians,
      neurological and psychiatric onset and age at death all displayed significant
      inverse correlations with CAG number indicating that diagnosis of onset is
      reasonably accurate, and that most patients die from the disease and its
      complications. Neuronal changes before clinical onset are not detected by
      conventional microscopic examination as three out of 15 'at risk' brains had an
      expanded CAG allele but no neuropathology. The cause of HD-like neuropathology in
      three exceptional brains from clinically diagnosed individuals is unclear. The
      disorder in these cases could be an HD phenocopy or result from alternative
      mutational mechanisms at the HD locus.

PMID- 9173996
TI  - Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue.
AB  - Dentatorubral pallidoluysian atrophy (DRPLA) is a rare, progressive, fatal
      neuropsychiatric disorder similar to Huntington's disease, caused by an expansion
      of a CAG trinucleotide repeat encoding glutamine. We have cloned the cDNA of the
      rat homologue of this gene. The cDNA contains a 3549 base pair open reading frame
      that is 88.2% identical to the human cDNA, with a predicted amino acid sequence
      that is 93.6% identical to the human sequence. The consecutive glutamine repeat
      is only five residues in length (normal range in human: 7-35 glutamines) and is
      followed by a polymorphic region of alternating glutamine and proline residues
      (QQQQQPQPQPQPQQ). The sequence also includes a polymorphic proline repeat, a
      serine repeat, and a region of alternating acidic and basic residues. Northern
      analysis and in situ hybridization indicate that the gene is widely expressed as
      a 4.5 kb mRNA, with a neuronal distribution in the brain. The widespread
      expression of this gene is consistent with the possibility that DRPLA, like other
      glutamine repeat diseases, is a result of an abnormality at the protein level.

PMID- 9173997
TI  - Age dependent sensitivity of the rat retina to the excitotoxic action of N-methyl
      D-aspartate.
AB  - We have found that the rat retina can be isolated atraumatically and incubated ex
      vivo for up to 24 h without showing signs of histological deterioration, and that
      retinas from adult or aged rats can be isolated as successfully as those from
      immature rats. In the present study we used this preparation to show that rat
      retinal neurones at postnatal day zero (PND 0) are relatively insensitive to the
      excitotoxic action of the glutamate agonist, N-methyl-D-aspartate (NMDA), then
      gradually show increasing sensitivity that peaks at about PND 9 and declines from
      PND 15-30 after which it remains at a low level up to the last time point studied
      (10 months of age). This is consistent with other developmental NMDA receptor
      data and underscores the need for caution in using immature in vitro central;
      nervous system (CNS) tissue preparations as a basis for interpreting the role of
      NMDA receptors in adult neurological diseases.

PMID- 9173998
TI  - Expression of neuronal nitric oxide synthase corresponds to regions of selective
      vulnerability to hypoxia-ischaemia in the developing rat brain.
AB  - Nitric oxide (NO) has been implicated in the pathogenesis of brain injury from
      hypoxia-ischaemia. In the brain, the enzyme responsible for NO synthesis is
      neuronal nitric oxide synthase (nNOS). Using in situ hybridization,
      immunohistochemistry and NADPH diaphorase histochemistry, we examined the spatial
      and temporal expression of nNOS during development of the rat brain to determine
      whether the expression of nNOS delineates the areas of the brain that are
      selectively vulnerable to hypoxic-ischaemia injury. The expression of nNOS was
      localized to discrete areas of the brain. nNOS could be detected in the
      developing forebrain in the 10-day-old embryo (E10). From E14 to E18, the highest
      level of expression was in the cortical plate, where the majority of neurons were
      positive. However, this expression diminished with time; in the adult there were
      only a few nNOS-positive neurones in the deep layers of the cortex. Expression of
      nNOS was not detected prenatally in the basal ganglia. There was transient high
      level expression during the first postnatal week. Thereafter, the basal ganglia
      exhibited the adult pattern of expression. Expression of nNOS could be detected
      in the hippocampus at E16. This expression remained constant with regional
      localization in layers CA1 and CA3 in the adult. Similarly, nNOS expression in
      the developing cerebellum was observed only after birth. From the first day after
      birth (P1) to P6, expression was limited to the molecular cell layer. As the
      cerebellum matured, nNOS expression could be detected in the inner granular
      layer. By P21, the adult distribution of nNOS expression was observed. All
      regions expressing nNOS mRNA also demonstrated nNOS protein expression and NADPH
      diaphorase catalytic activity. Our results demonstrate that nNOS expression in
      the developing brain correlates with regions of selective vulnerability to
      hypoxic-ischaemic injury, and, therefore, supports a role for NO in hypoxic
      ischaemic injury in the developing brain.

PMID- 9173999
TI  - Overexpression of Bcl-2 attenuates MPP+, but not 6-ODHA, induced cell death in a
      dopaminergic neuronal cell line.
AB  - In order to investigate the role of Bcl-2 in dopaminergic cells, we established a
      dopaminergic neuronal cell line (MN9D) stably expressing human Bcl-2 (MN9D/Bcl-2)
      or neomycin (MN9D/Neo). Overexpression of Bcl-2 in MN9D cells attenuated cell
      death due to treatment of mitochondrial electron transport inhibitors including N
      methyl-4-phenylpyridinium, whereas it did not prevent cell death induced by
      reagents generating reactive oxygen species including 6-hydroxy-dopamine.
      Moreover, the rate of glucose uptake in MN9D/Bcl-2 was significantly lower than
      that in MN9D/Neo after MPP+ treatment. Thus, Bcl-2 may counter aberrations in
      mitochondrial electron transfer processes by altering energy metabolism within
      the MN9D cells.

PMID- 9174000
TI  - Identification of a unique apolipoprotein E allele in Microcebus murinus; ApoE
      brain distribution and co-localization with beta-amyloid and tau proteins.
AB  - This report is devoted to the characterization of the apolipoprotein E (ApoE) in
      Microcebus murinus. Only one allele homologous to the human ApoE4 allele was
      evidenced. The distribution of the corresponding ApoE protein in the brain was
      found in association with the pathological proteins characteristic of Alzheimer's
      disease (AD). Immunocytochemistry revealed brain deposits of ApoE in: (1) the
      cortical amyloid plaques; (2) the neurones of the various cortical lobes, the
      hippocampus and the brainstem; (3) the glial cells, astrocytes of the cortical
      parenchym and oligodendrocytes of the corpus callosum; and (4) the vessel walls.
      Most ApoE, beta-amyloid protein, abnormally phosphorylated Tau proteins and
      gliofilament acid proteins were seen in the same cortical areas. These findings
      for ApoE report the view that Microcebus murinus, in captivity, presents a
      pathological profile very similar to that observed in AD.

PMID- 9174001
TI  - Co-expression of beta-amyloid precursor protein (betaAPP) and apolipoprotein E in
      cell culture: analysis of betaAPP processing.
AB  - Apolipoprotein E (ApoE) is the major genetic risk factor for Alzheimer's disease
      (AD). The ApoE4 allele is associated with earlier disease onset and greater
      cerebral deposition of the amyloid beta peptide (Abeta), the major constituent of
      senile (amyloid) plaques. The molecular mechanism underlying these effects of
      ApoE4 remains unclear; ApoE alleles could have different influences on Abeta
      production, extracellular aggregation, or clearance. Because the missense
      mutations on chromosomes 14 and 21 that cause familial forms of AD appear to lead
      to increased secretion of Abeta, it is important to determine whether ApoE4 has a
      similar effect. Here, we have examined the effects of all three ApoE alleles on
      the processing of betaAPP and the secretion of Abeta in intact cells. We
      established neural (HS683 human glioma) and non-neural (Chinese hamster ovary)
      cell culture systems that constitutively secrete both ApoE and Abeta at
      concentrations like those in human cerebrospinal fluid. betaAPP metabolites,
      generated in the presence of each ApoE allele, were analysed and quantified by
      two methods: immunoprecipitation and phosphorimaging, and ELISA. We detected no
      consistent allele-specific effects of ApoE on betaAPP processing in either cell
      type. Our data suggest that the higher amyloid burden found in AD subjects
      expressing ApoE4 is not due to increased amyloidogenic processing of betaAPP, in
      contrast to findings in AD linked to chromosome 14 or 21. These co-expressing
      cell lines will be useful in the further search for the effects of ApoE on Abeta
      aggregation or clearance under physiologically relevant conditions.

PMID- 9174022
TI  - Arteriovenous malformation of the vein of Galen in children.
AB  - Arteriovenous malformation of the vein of Galen (VGM) is a unique vascular
      anomaly in children. Its extra parenchymal location allows for aggressive
      endovascular treatment. Depending on the age of the child, the clinical
      presentation of VGM varies from congestive heart failure to hydrocephalus. The
      deleterious consequences to the brain depend on many factors, the most important
      of which is the volume of blood shunting through the malformation and away from
      the brain parenchyma ("steal" phenomenon). High flow in a fetus with a developing
      brain will lead not only to brain ischemia but also to multiple organ failure. At
      the other end of the spectrum, a small malformation can be well tolerated.
      Treatment should be tailored to each individual case.

PMID- 9174023
TI  - "Cold bone scans" as a sign of hemorrhagic infarcts of the spine in Gaucher's
      disease.
AB  - The most common form of Gaucher's disease, type 1 (chronic non-neuronopathic),
      results in accumulation of glucocerebroside in reticuloendothelial cells of the
      spleen, liver and bone marrow, with frequent occurrence of bone pain due to vaso
      occlusive crisis. We report the finding of a "cold" vertebral body on bone scan
      in two patients with Gaucher's disease and bone crisis. Photopenia was so
      striking as to give the appearance of a "missing" vertebra. Concurrent plain
      films appeared normal. In one patient Gaucher's disease had not previously been
      diagnosed.

PMID- 9174024
TI  - The value of MRI in early Perthes' disease: an MRI study with a 2-year follow-up.
AB  - Eleven hips in nine patients with Perthes' disease were studied by plain
      radiography at 3-month and MRI at 6-month intervals over a period of 2 years. The
      aim was to clarify the value of MRI in estimating epiphyseal involvement and in
      predicting uncoverage of the epiphysis. Signal intensities of the epiphysis and
      metaphysis were visually evaluated from T1- (T1W) and T2-weighted (T2W) images.
      The extent of decreased signal intensity (DSI) in the epiphyses was
      volumetrically calculated from T1W images and then compared with follow-up
      radiographs. The area of epiphyseal DSI corresponding best with Catterall's
      classification was seen by MRI 3-8 months after the first symptoms. MRI images
      obtained earlier usually showed less involvement than the follow-up radiographs.
      However, two features predicting extensive epiphyseal necrosis were: (1) DSI on
      both T1W and T2W images covering over two-thirds of the epiphysis and (2) diffuse
      bone marrow oedema of the femoral neck and metaphysis. When T1W images showed a
      reappearance of high signal intensity patches in the lateral quarter of the
      epiphysis, no clinically significant uncoverage was seen during the follow-up.
      Extensive epiphyseal necrosis can, therefore, sometimes be predicted by MRI even
      within the first 3 months, but MRI visualises epiphyseal involvement more clearly
      3-8 months after the first symptoms.

PMID- 9174025
TI  - Abdominal calcification in cystic fibrosis with meconium ileus: radiologic
      pathologic correlation.
AB  - BACKGROUND: There is confusion in the radiological literature as to the site of
      abdominal calcification in cystic fibrosis (CF) with meconium ileus (MI) in
      neonates. PURPOSE: To correlate the site of radiographic abdominal calcification
      with histologic and operative findings. MATERIALS AND METHODS: A review of
      clinical, radiographic, surgical and histologic data in 58 neonates with CF and
      MI. RESULTS: Abdominal calcification was identified in 15 (26 %) neonates: on an
      abdominal radiograph in 8 (13 %), at laparotomy in 3 and histologically in 10 (37
      %) of the 27 resected specimens. The radiographic pattern of calcification varied
      from small specks in three cases to small, better-defined areas in two. In the
      other three patients, the calcification was more extensive and curvilinear.
      Histologically, calcification was found to be intramural in ten resected
      specimens, of which two also had intraluminal and one serosal calcification. The
      more extensive, curvilinear calcification identified radiographically correlated
      with histologically proven dystrophic intramural calcification. The less marked
      flecks or discrete areas of radiographic calcification may represent intramural,
      serosal or intraluminal calcification. CONCLUSION: Intramural calcification is
      common microscopically in CF with MI. Extensive radiographic calcification in
      these patients is more likely to represent intramural rather than serosal or
      intraluminal calcification.

PMID- 9174026
TI  - An unusual position of the gallbladder following nephrectomy for large neoplasms.
AB  - The cases of two children are presented in whom the gallbladder was found to lie
      in an unusual position in the ipsilateral renal fossa following nephrectomy for
      large neoplasms. This postoperative visceral position must be recognized, as the
      appearance on cross-sectional imaging can mimic postoperative fluid collections
      at the resection site or tumor recurrence.

PMID- 9174028
TI  - Disappearing fetal lung masses: importance of postnatal imaging studies.
AB  - BACKGROUND: The "disappearance" of congenital masses of the lung on prenatal
      sonograms has been described, but the importance of postnatal imaging studies in
      these children is unknown. OBJECTIVE: The objective of this work was to study the
      utility of radiographs and CT scans in asymptomatic infants with congenital
      masses of the lung that partially or completely resolve on prenatal sonograms
      performed late in gestation. MATERIALS AND METHODS: The prenatal sonograms,
      postnatal imaging studies, surgical findings, and pathologic diagnoses of seven
      children with an echogenic mass of the lung that improved or disappeared on
      prenatal sonograms were reviewed. RESULTS: All masses were type II congenital
      cystic adenomatoid malformation, with features of intralobar sequestration also
      being found in four. An unsuspected extralobar sequestration adjacent to a left
      lower lobe mass was found at surgery in one patient. All masses were hyperechoic
      compared with normal lung on sonograms prior to 32 weeks of gestation, with cysts
      being seen in four. On scans after 32 weeks, four of the masses had resolved
      completely and three showed subtle increased echogenicity compared with normal
      lung. Cysts completely resolved in two of four cases. Postnatal radiographs
      showed subtle abnormalities in four infants, a hyperlucent lobe in one, a soft
      tissue mass with adjacent hyperlucency in one, and normal findings in one. CT
      scans were abnormal in all cases, with air-filled cysts and soft tissue in six
      and a hyperinflated lobe in one. CONCLUSION: Children with "disappearing" fetal
      lung masses have persistent abnormalities after birth that are often subtle on
      radiographs but are well demonstrated with CT.

PMID- 9174027
TI  - Esophageal atresia/tracheoesophageal fistula and associated congenital esophageal
      stenosis.
AB  - BACKGROUND: The association of congenital stenosis of the distal esophagus (CES)
      in children with esophageal atresia/tracheoesophageal fistula complex (TEF) has
      been described but is thought to be rare. Most reports have been of individual or
      small numbers of cases. OBJECTIVE: The objective of the study was to evaluate the
      incidence, clinical and radiographic features of CES associated with TEF, and to
      compare the clinical and radiographic features of CES with acquired anastomotic
      strictures in TEF patients. MATERIALS AND METHODS: A retrospective review was
      undertaken of the records and radiographs of 225 infants with primary TEF repair
      over a 26-year period. RESULTS: A total of 18 of 225 (8 %) cases of CES
      associated with TEF and 43 of 225 (19 %) cases of anastomotic strictures were
      identified. CES was typically a relatively long, smooth circumferential narrowing
      at the junction of the mid-esophagus and distal esophagus, with normal-caliber
      esophagus above and below; anastomotic strictures, in contrast, were focal.
      Diagnosis of CES was delayed in 10 cases and missed on one or more fluoroscopic
      studies in 14 children. Symptoms, including feeding and respiratory problems and
      foreign body impaction, were common in both CES and anastomotic strictures;
      repeated esophageal dilatations were usually necessary. Esophageal perforation
      complicated dilatation in 6 (33 %) young children with CES, but none of the
      children with anastomotic strictures (P < 0.001). CONCLUSION: CES in combination
      with TEF is not rare and usually produces clinical symptoms. The diagnosis may be
      missed or delayed unless specifically evaluated surgically and radiologically.
      Esophageal dilatation in CES is potentially hazardous with a high risk of
      perforation, especially in young children.

PMID- 9174029
TI  - CT scan abnormalities in a series of patients with hemorrhagic shock and
      encephalopathy syndrome.
AB  - BACKGROUND: Hemorrhagic shock and encephalopathy syndrome (HSES) affects children
      under 1 year of age and is characterized by seizures, shock and certain
      laboratory abnormalities, including coagulation abnormalities. It has a high
      mortality and many of the survivors are neurologically abnormal. OBJECTIVE: To
      describe abnormalities observed on initial and follow-up CT scans in a group of
      patients suffering from HSES. MATERIALS AND METHODS: Retrospective review of
      records and CT scans of ten patients with HSES who were admitted to the intensive
      care unit of the Children's Hospital and Medical Center, Seattle. RESULTS:
      Cerebral edema was seen in all cases when the CT scan was obtained between 1 and
      7 days after onset of HSES. The basal ganglia and cerebellum were relatively
      spared, and no hemorrhage was seen. Patients with moderate or marked cerebral
      edema usually had a poor prognosis. All survivors had significant neurologic
      sequelae. CT scans obtained after 7 days often showed encephalomalacia with ex
      vacuo ventricular enlargement. CT scans obtained between 24 h and 4 days after
      onset will show the acute changes of HSES. CT scans during the initial and
      convalescent stages of HSES can provide useful information about cerebral edema
      and encephalomalacia, which occur frequently with this illness.

PMID- 9174030
TI  - Fast fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging of
      the brain: a comparison of multi-shot echo-planar and fast spin-echo techniques.
AB  - PURPOSE: To evaluate fast spin-echo and multi-shot echo-planar fluid-attenuated
      inversion recovery (FLAIR) sequences in paediatric brain imaging. MATERIALS AND
      METHODS: Matched images from 32 patients with suspected tumour or white matter
      disease were independently evaluated by two paediatric neuroradiologists. The
      observer preferences for image quality and lesion detection were analysed for
      differences between fast spin-echo FLAIR and multi-shot echo-planar FLAIR.
      Diagnostic quality was compared with that of fast spin-echo T2-weighted images.
      RESULTS: Images of a diagnostic quality equivalent to that of fast spin-echo T2
      weighted images were achieved with both FLAIR techniques. Grey and white matter
      differentiation and cerebrospinal fluid (CSF) nulling were significantly better
      on fast spin-echo FLAIR sequences. CSF flow artefact was reduced on multi-shot
      echo-planar FLAIR. There was no difference in lesion detection. Fast spin-echo
      FLAIR images were visually preferred at the expense of longer imaging time.
      CONCLUSION: Fast FLAIR techniques are complementary to fast spin-echo T2-weighted
      sequences in imaging of the paediatric brain. We find that the fast spin-echo
      FLAIR sequence is preferable to the multi-shot echo-planar technique.

PMID- 9174031
TI  - Large adrenal cysts in teenage girls: diagnosis and management.
AB  - Large adrenal cysts usually occur in the fifth and sixth decades of a patient's
      life but are rare in the first two decades. This paper presents the clinical,
      cross-sectional imaging, surgical, pathological and follow-up data of three
      teenage girls with large adrenal cysts. Two had vague upper abdominal pain and,
      in the other, the cyst was found incidentally. The cysts were surgically removed
      in two patients, while in the third, follow-up imaging has shown no change in the
      cyst over a 4-year period, suggesting that conservative management is a
      reasonable option.

PMID- 9174032
TI  - Correlation of cystographic bladder morphology and neuroanatomy in boys with
      posterior urethral valves.
AB  - PURPOSE: We have observed a difference in the radiographic appearance of the body
      of the bladder (trabeculated) and its base (smooth) in boys with severely
      obstructing posterior urethral valves. We wanted to determine if (1) this was a
      reproducible finding and (2) there was an anatomic and/or physiologic explanation
      for it. MATERIALS AND METHODS: We reviewed the initial voiding cystourethrogram
      in 47 boys with severe posterior urethral valves. The interureteric ridge was
      used as the division between the body and base of the bladder. The presence of
      trabeculation for each region was recorded. RESULTS: Ages ranged from 1 day to 6
      years at the time of initial cystographic evaluation (median 14 days). The body
      of the bladder was trabeculated and the base smooth in 72 % (34 patients). In the
      remaining patients, both the body and base were smooth. In no patient was the
      base trabeculated. CONCLUSIONS: The cystographic morphology of the urinary
      bladder in boys with posterior urethral valves can be explained by its
      neuroanatomy. The body of the bladder, which contracts during voiding because of
      parasympathetic (cholinergic) stimulation, becomes trabeculated. The bladder base
      relaxes during voiding due to sympathetic (alpha adrenergic) stimulation and
      remains smooth. Thus, this difference in the cystographic appearance of the two
      parts of the urinary bladder reflects the normal innervation and the mechanics of
      micturition in boys with urethral obstruction.

PMID- 9174033
TI  - Leiomyosarcoma of the kidney in an HIV-infected child.
AB  - Spindle cell tumors (leiomyoma and leiomyosarcoma) have been described in
      immunocompromised children after transplantation and in association with HIV
      infection. Previous reports have described tumors of respiratory (lung, bronchi),
      gastrointestinal (stomach, bowel, liver), and subcutaneous origins. We report a
      case of leiomyosarcoma of the kidney in an HIV-infected child.

PMID- 9174034
TI  - Mid-ureteric cyst: a variant of ureterocele disproportion.

PMID- 9174035
TI  - Cerebral infarction in children with high levels of anticardiolipin antibody.

PMID- 9174036
TI  - Double blind ureteral duplication.

PMID- 9174037
TI  - Office procedures. Education, training, and proficiency of procedural skills.
AB  - Clinical competence exists when a practitioner has sufficient knowledge and skill
      such that a procedure can be performed to obtain intended outcomes without harm
      to the patient. Practitioners who want to be competent in performing clinical
      procedures should examine how the procedures are relevant to their practice,
      place the procedures in a familiar context, learn what outcomes are expected, and
      practice self-evaluation. Competence has several components, including knowledge,
      clinical decision making, judgment, technical skills, attitudes, professional
      habits, and interpersonal skills. Each of these must be mastered using a variety
      of sources of information and skill acquisition.

PMID- 9174038
TI  - Office procedures. Colposcopy.
AB  - Colposcopy is a clinical procedure to examine the epithelium of the uterine
      cervix and surrounding anogenital area with a magnifying instrument to detect the
      presence of cervical neoplasia and to identify abnormal tissue for biopsy. The
      procedure is enhanced by the use of chemical solutions that assist discrimination
      of normal tissue and abnormal lesions. Colposcopic examination and directed
      biopsy of the most severe focus of cervical neoplasia ensure a valid
      representation of the status of cervical disease. The results from the cytologic
      smear, histologic evaluation, and colposcopic impression collectively determine
      appropriate patient management.

PMID- 9174039
TI  - Office procedures. Cryotherapy of dermal abnormalities.
AB  - Cryotherapy of dermal abnormalities is a commonly used technique in the field of
      primary care. To perform cryotherapy effectively, one must understand the
      principles of cryoablation and how they apply to specific skin disorders. One
      also must be familiar with the various types of equipment that are used to
      perform cryotherapy. With this understanding cryotherapy easily can be integrated
      into outpatient primary care.

PMID- 9174040
TI  - Office procedures. Electrosurgical loop excision of the cervix.
AB  - This article discusses the technique of cervical electrosurgical loop excision,
      which allows for treatment of premalignant conditions of the cervix. The primary
      goal of cervical loop excision is to provide a method of managing preneoplastic
      cervical conditions in a safe, effective manner while minimizing the chance of
      missing invasive cancer. Topics discussed include equipment and supplies,
      procedural pearls, complications, and so forth.

PMID- 9174041
TI  - Office procedures. Endometrial biopsy.
AB  - Endometrial biopsy is a relatively safe, efficient, and well-tolerated procedure.
      Indications include evaluation of abnormal uterine bleeding and infertility.
      Excluding the presence of endometrial cancer and precursors is of primary
      concern. Use of the popular narrow polyethylene sampling devices results in a
      sensitivity approaching 95% for the diagnosis of endometrial cancer. Inadequate
      samples are more common in postmenopausal than premenopausal women, primarily
      because of atrophy of the endometrium.

PMID- 9174042
TI  - Office procedures. Esophagogastroduodenoscopy.
AB  - This article describes diagnostic esophagogastroduodenoscopy and its use by
      primary care physicians. Included in the discussion are reviews of indications
      and contraindications, patient preparation (including sedation and monitoring),
      equipment and supplies needed, pertinent normal anatomy, techniques, and
      applicable common pathologic findings.

PMID- 9174043
TI  - Office procedures. Flexible sigmoidoscopy.
AB  - The flexible sigmoidoscope is a flexible fiberoptic or video endoscope designed
      to examine the mucosal surface of the sigmoid colon and rectum. The flexible
      sigmoidoscope represents a technologic advancement over the earlier rigid
      sigmoidoscopes that were hindered by the relatively short length of bowel they
      could visualize and the rather uncomfortable examination the patient was required
      to endure in its use. It has clinical usefulness in the evaluation of many
      disease processes that involve the rectum and sigmoid colon.

PMID- 9174044
TI  - Office procedures. Nasopharyngoscopy.
AB  - Patients who present to clinicians with complaints referable to the upper airway
      often benefit from careful visualization of the nasopharyngeal structures. The
      purpose of nasopharyngoscopy is to examine the pertinent structures of the upper
      airway. The patient benefits from a more accurate diagnosis and appropriate
      therapy. Flexible nasopharyngoscopy provides a valuable tool that primary care
      physicians can use effectively in the care of their patients.

PMID- 9174045
TI  - Office procedures. Exercise testing.
AB  - Exercise testing is an effective method for evaluating patients with chest pain,
      for diagnosing and managing coronary artery disease, for determining prognosis in
      patients with known coronary disease, for determining exercise capacity, for
      evaluating exercise-induced arrhythmias, for verifying the safety of exercise,
      and for customizing an exercise prescription. With proper clinician training and
      careful selection of patients, exercise testing is a safe procedure (less than 1
      complication per 10,000 cases). Performing office-based exercise testing improves
      clinician's basic electrocardiograph reading capabilities, communication, and his
      or her referral patterns with subspecialists. With an understanding of the basic
      principles of exercise testing, with proper supervision or consultation, and with
      proper selection of patients, most clinicians can enjoy exercise testing safely.

PMID- 9174046
TI  - Office procedures. Obstetric ultrasonography.
AB  - Some clinician physicians who provide perinatal care find that they have the
      motivation and practice volume to learn diagnostic ultrasonographic skills. These
      skills may be limited to labor and delivery applications or may extend to
      performance of the standard antepartum obstetric ultrasound examination. Limited
      skills include the diagnosis of fetal life number, presentation, amniotic fluid
      assessment, and placental localization. The standard antepartum obstetric
      ultrasound examination adds fetal biometry and a detailed assessment of fetal
      anatomy.

PMID- 9174047
TI  - Office procedures. No-scalpel vasectomy.
AB  - Vasectomy is a safe, permanent, and inexpensive method of surgical sterilization
      for men. No-scalpel vasectomy is an innovative approach for exposing the vas
      deferens that is associated with fewer complications than the standard technique
      of vasectomy (incisional). It has been used in this country since 1986. The no
      scalpel vasectomy, preoperative counseling, management of complications, and
      evaluation of the postvasectomy semen specimen are described.

PMID- 9174048
TI  - Cells lacking CIP1/WAF1 genes exhibit preferential sensitivity to cisplatin and
      nitrogen mustard.
AB  - We have previously shown that p53 disruption sensitizes certain cancer cell types
      to cisplatin (CDDP) (Fan et al., 1995). In the present study we investigated the
      role of the p53 downstream effector, p21CIP1/WAF1 (p21), in this sensitization.
      Studies were performed in human colon cancer HCT-116 cells and murine embryonic
      fibroblasts (MEF) with intact versus disrupted p21 genes. For comparison, HCT-116
      cells lacking p53 function were also prepared through stable transfection with
      the human papillomavirus type-16 E6 gene. HCT-116/E6 cells were found to be more
      sensitive than control transfectants to CDDP and another DNA crosslinking agent,
      nitrogen mustard (HN2). HCT-116 cells with disrupted p21 genes also exhibited
      greater CDDP and HN2-sensitivity than parental HCT-116 cells. In contrast, the
      clonogenic survival of HCT-116 cells exposed to ionizing radiation, adriamycin,
      taxol or vincristine was not affected by p53 or p21 disruption. Sensitization of
      HCT-116/p21-/- cells to CDDP and HN2 was not limited to the HCT-116 cell
      background since MEF from p21 knockout mice were also more sensitive to these DNA
      crosslinking agents. Investigations into a possible cause of this enhanced
      sensitivity revealed that HCT-116 cells lacking p53 or p21 function exhibited a
      reduced ability to repair cisplatin-damaged CAT-reporter plasmids transfected
      into the cells. In addition, we found that HCT-116/p21-/- cells were much more
      susceptible to HN2-induced cell cycle delay than parental cells. Our results
      suggest that p21 disruption preferentially sensitizes at least some cell types to
      DNA crosslinking agents.

PMID- 9174049
TI  - Dissociation between cell cycle arrest and apoptosis can occur in Li-Fraumeni
      cells heterozygous for p53 gene mutations.
AB  - The radiation response was investigated in two lymphoblastoid cell lines (LBC)
      derived from families with heterozygous germ-line missense mutations of p53 at
      codon 282 (LBC282) and 286 (LBC286), and compared to cells with wt/wt p53(LBC-N).
      By gel retardation assays, we show that p53-containing nuclear extracts from
      irradiated LBC282 and LBC286 markedly differ in their ability to bind to a p53
      DNA consensus sequence, the former generating a shifted band whose intensity is
      30-40% that of LBC-N, the latter generating an almost undetectable band. Unlike
      LBC286, which fail to arrest in G1 after irradiation, LBC282 have an apparently
      normal G1/S checkpoint, as they arrest in G1, like LBC-N. While in LBC-N,
      accumulation of p53 and transactivation of p21WAF1 increase rapidly and markedly
      by 3 h after exposure to gamma-radiation, in LBC286 there is only a modest
      accumulation of p53 and a significantly delayed and quantitatively reduced
      transactivation of p21WAF1. Instead, in LBC282 while p53 levels rise little after
      irradiation, p21WAF1 levels increase rapidly and significantly as in normal LBC.
      Apoptotic cells present 48 h after irradiation account for 32% in LBC-N, 8-9% in
      LBC282 and 5-7% in LBC286, while the dose of gamma-radiation required for killing
      50% of cells (LD50) is 400 rads, 1190 rads and 3190 rads, respectively, hence
      indicating that the heterozygous mutations of p53 at codon 282 affects
      radioresistance and survival, but not the G1/S cell cycle control. In all LBC
      tested, radiation-induced apoptosis occurs in all phases of the cell cycle and
      appears not to directly involve changes in the levels of the apoptosis-associated
      proteins bcl-2, bax and mcl-1. Both basal as well as radiation-induced p53 and
      p21WAF1 proteins are detected by Western blotting of FACS-purified G1, S and G2/M
      fractions from the three cell lines. p34CDC2-Tyr15, the inactive form of p34CDC2
      kinase phosphorylated on Tyr15, is found in S and G2/M fractions, but not in G1.
      However, 24 h after irradiation, its levels in these fractions diminish
      appreciably in LBC-N but not in the radioresistant LBC286 and LBC282.
      Concomitantly, p34CDC2 histone H1 kinase activity increases in the former, but
      not in the latter cell lines, hence suggesting a role for this protein in
      radiation-induced cell death. Altogether, this study shows that, in cells
      harbouring heterozygous mutations of p53, the G1 checkpoint is not necessarily
      disrupted, and this may be related to the endogenous p53 heterocomplexes having
      lost or not the capacity to bind DNA (and therefore transactivate target genes).
      Radiation-induced cell death is not cell cycle phase specific, does not involve
      the regulation of bcl-2, bax or mcl-1, but is associated with changes in the
      phosphorylation state and activation of p34CDC2 kinase.

PMID- 9174050
TI  - Altered expression of Erg and Ets-2 transcription factors is associated with
      genetic changes at 21q22.2-22.3 in immortal and cervical carcinoma cell lines.
AB  - Human Papillomavirus (HPV) type 16 is the most frequently detected HPV in
      cervical cancer. Although epidemiologic and experimental evidence indicates a
      prominent role for HPV infection in the development of this disease, other
      factors are also involved. Altered expression of the ets family transcription
      factors erg and ets-2 was found associated with the development of cervical
      carcinoma. Overexpression also occurred in a HPV-16-immortalized cervical cell
      line, CX16-2, which has HPV integrated at a translocation breakpoint t(19;21)
      involving 21q22.2-22.3, where these genes have been mapped. Six of 10 cervical
      carcinoma cell lines overexpressed ets-2 RNA suggesting an association of
      overexpression with cervical cell neoplasia. A clonally related pair of cervical
      carcinoma cell lines, C-4I and C-4II, showed differential expression of erg and
      ets-2. C-4I overexpressed ets-2 RNA compared to normal cervical cells and C-4II.
      C-4II expressed a 5.3 kb erg transcript not seen in C-4I, ectocervical cells or
      other cervical carcinoma cell lines examined. Pulsed field gel electrophoresis
      was used to analyse changes in DNA fragments related to structural changes and to
      construct a physical map encompassing erg and ets-2. Alterations in erg and ets-2
      RNA expression in each of three different cell lines examined were associated
      with translocations. Association between altered expression of erg and ets-2 and
      altered regional structural suggests that these genes are important targets in
      cervical carcinogenesis.

PMID- 9174051
TI  - Identification of XLerk, an Eph family ligand regulated during mesoderm induction
      and neurogenesis in Xenopus laevis.
AB  - We have isolated and characterized the first Xenopus transmembrane Eph ligand,
      XLerk (Xenopus Ligand for Eph Receptor Tyrosine Kinases). While this ligand has
      72% identity with the closest mammalian family member, Lerk-2, it is the
      cytoplasmic domain of this molecule that is the most conserved domain with 95%
      identity. XLerk exists as a maternally expressed mRNA, however, expression of
      transcripts and protein increase during gastrulation and again in the late
      swimming tadpole stage. In the adult, XLerk is expressed at low levels in most
      adult tissues with increased levels observed in the kidney, oocytes, ovary and
      testis. While low levels of XLerk expression are observed in the adult brain, in
      situ hybridization analysis demonstrates prominent expression in the developing
      olfactory system, retina, hindbrain, cranial ganglia, and somites. Furthermore,
      we have shown that XLerk transcripts are significantly elevated during mesoderm
      induction caused by activin and FGF, but not during noggin-induced neuralization.
      These results suggest a role for XLerk in the developing mesenchymal and nervous
      tissue.

PMID- 9174052
TI  - A link between metastasis and resistance to apoptosis of variant small cell lung
      carcinoma.
AB  - A novel human gene CC3 with properties of a metastasis suppresor gene for small
      cell lung carcinoma (SCLC) is described. CC3 is an evolutionary conserved gene
      that is expressed ubiquitously in human tissues. CC3 RNA is absent in a subset of
      SCLC cell lines known as variant (v-SCLC) that are derived from tumors
      characterized by highly aggressive metastatic behavior. Introduction of CC3 into
      a variant SCLC line results in significant suppression of its metastasis in vivo.
      When deprived of growth factors in vitro, v-SCLC cells modified to express CC3
      undergo rapid and massive cell death that at least partially could be ascribed to
      the activation of the apoptotic pathway. In addition, expression of CC3 in v-SCLC
      cells increases induction of apoptosis by chemoterapeutic drugs. Loss of CC3 in
      highly metastatic cells such as SCLC might render them resistant to death
      inducing signals and thus help to ensure their survival under unfavorable
      conditions encountered in the metastatic process.

PMID- 9174053
TI  - ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma,
      encodes a novel neural receptor tyrosine kinase that is highly related to
      leukocyte tyrosine kinase (LTK)
AB  - Anaplastic Lymphoma Kinase (ALK) was originally identified as a member of the
      insulin receptor subfamily of receptor tyrosine kinases that acquires
      transforming capability when truncated and fused to nucleophosmin (NPM) in the
      t(2;5) chromosomal rearrangement associated with non-Hodgkin's lymphoma, but
      further insights into its normal structure and function are lacking. Here, we
      characterize a full-length normal human ALK cDNA and its product, and determine
      the pattern of expression of its murine homologue in embryonic and adult tissues
      as a first step toward the functional assessment of the receptor. Analysis of the
      6226 bp ALK cDNA identified an open reading frame encoding a 1620-amino acid (aa)
      protein of predicted mass approximately 177 kDa that is most closely related to
      leukocyte tyrosine kinase (LTK), the two exhibiting 57% aa identity and 71%
      similarity over their region of overlap. Biochemical analysis demonstrated that
      the approximately 177 kDa ALK polypeptide core undergoes co-translational N
      linked glycosylation, emerging in its mature form as a 200 kDa single chain
      receptor. Surface labeling studies indicated that the 200 kDa glycoprotein is
      exposed at the cell membrane, consistent with the prediction that ALK serves as
      the receptor for an unidentified ligand(s). In situ hybridization studies
      revealed Alk expression beginning on embryonic day 11 and persisting into the
      neonatal and adult periods of development. Alk transcripts were confined to the
      nervous system and included several thalamic and hypothalamic nuclei; the
      trigeminal, facial, and acoustic cranial ganglia; the anterior horns of the
      spinal cord in the region of the developing motor neurons; the sympathetic chain;
      and the ganglion cells of the gut. Thus, ALK is a novel orphan receptor tyrosine
      kinase that appears to play an important role in the normal development and
      function of the nervous system.

PMID- 9174054
TI  - Infrequency of BRCA2 alterations in head and neck squamous cell carcinoma.
AB  - Alterations of BRCA2 result in increased susceptibility to breast cancer in both
      men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps
      to 13q12-q13 and encodes a transcript of 10,157 bp. Other cancers that have been
      described in BRCA2 mutation carriers include those of the larynx. Human
      chromosome 13q has been shown previously by LOH studies to harbor several tumor
      suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore
      examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%)
      of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing
      region. These and 10 other HNSCCs of different origins that were demonstrated by
      LOH studies to have lost the region of chromosome 13 containing BRCA2 were
      examined for alterations in this gene. SSCP analysis failed to reveal any
      alterations leading us to conclude that BRCA2 alterations are not frequently
      involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13
      loci is due to other, as yet, unidentified tumor suppressor gene(s).
      Interestingly tumors with LOH in this region (proximal to D13S118) were far more
      likely to be derived from women than men. This is unusual since HNSCCs are
      usually fourfold more common in men than in women.

PMID- 9174055
TI  - A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is
      amplified and overexpressed in human breast cancer cell lines.
AB  - DNA amplification on chromosome 20q13 is commonly detected in breast cancer and
      correlates with poor prognosis. Definitive critical target genes on this amplicon
      have however, not yet been identified. We describe in this paper isolation of a
      novel gene named BTAK, encoding a putative member of protein serine/threonine
      kinase family localized on chromosome 20q13 that is amplified and overexpressed
      in breast tumor cell lines. BTAK maps close to the critical region of
      amplification defined earlier on this amplicon. Deduced amino acid sequence shows
      conservation of all the subdomains predicted in protein kinase super family.
      Translated BTAK peptide shows significant homology with previously cloned protein
      serine/threonine kinase encoding genes Ip11 from S cerevisae and aurora from
      Drosophila, both shown to be functionally involved in normal chromosome
      segregation process. Our findings suggest that amplification and overexpression
      of BTAK may be playing a critical role in oncogenic transformation of breast
      tumor cells.

PMID- 9174057
TI  - Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer.
AB  - The ARP gene encodes a highly conserved arginine-rich protein from chromosomal
      band 3p21.1. At the cytogenetic level this region is frequently deleted in a
      variety of different solid tumors, although not in pancreatic cancer. We have
      reported the presence of a specific mutation (ATG50-->AGG) or deletion of codon
      50 of the ARP gene in different tumor types (Shridhar et al., 1996, 1996a). In
      the present study, we have observed mutations involving codon 50 in 11 of 37
      pancreatic tumors. The frequency of codon 50 mutation is roughly the same in
      pancreatic tumors as in the other types of tumors previously examined. In
      addition, we have detected mutations at codon 51 in multiple PCR subclones in two
      other pancreatic tumors. Mutations in the ARP gene are thus commonly observed in
      pancreatic cancer, as well as many other cancers.

PMID- 9174056
TI  - Nuclear accumulation of fibroblast growth factor receptors in human glial cells-
      association with cell proliferation.
AB  - In this study we describe the presence of high affinity FGF-2 binding sites in
      the nuclei of U251MG glioma cells (K(d)=7 pM). Immunoprecipitation of total cell
      extracts with FGF receptor (FGFR) 1-4 antibodies showed that U251MG glioma cells
      express only FGFR1. [125I]FGF-2 cross linking to nuclear extracts followed by
      FGFR1 immunoprecipitation showed that FGFR1 may account for the nuclear FGF-2
      binding sites. Western blot analysis demonstrated the presence of 103, 118 kDa
      and small amounts of 145 kDa FGFR1 isoforms in the nuclei of glioma cells. All
      isoforms contain both the C- and N-terminal domains. Nuclear FGFR1 retains kinase
      activity. Immunocytochemistry using confocal microscopy showed specific FGFR1
      immunoreactivity within the nuclear interior. In continuously proliferating
      glioma cells, nuclear FGFR1 is constitutively expressed, independent of cell
      density. In contrast, in nontransformed human astrocytes, nuclear FGFR1 levels
      fluctuate with the proliferative state of the cell. In quiescent, confluent
      astrocytes nuclear FGFR1 protein was depleted. An accumulation of nuclear FGFR1
      was observed following the transition to a subconfluent, proliferating state.
      Transfection of a pcDNA3.1-FGFR1 expression vector into glioma cells that do not
      express FGFR1 resulted in the nuclear accumulation of FGFR1, increased cell
      proliferation, and stimulated transition from the G0/G1 to the S-phase of the
      cell cycle. The increased proliferative rate was resistant to inhibition by the
      cell-impermeable FGF binding antagonist, myoinositol hexakis [dihydrogen
      phosphate]. Our results suggest that the constitutive nuclear presence of FGFR1
      contributes to the increased proliferation of glioma cells while the transient
      nuclear accumulation of FGFR1 in normal astrocytes may play a role in the
      transition to a reactive state.

PMID- 9174058
TI  - Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells
      mediates enhanced association with phosphatidylinositol 3-kinase.
AB  - Increased tyrosine kinase activity of abl oncogene in Philadelphia chromosome
      positive-leukemic cells leads to activation of p21ras and phosphatidylinositol 3'
      kinase (PI 3-Kinase). The mechanism of activation of these signaling pathways is
      not understood, but numerous studies have focused on the identification and
      characterization of downstream substrates of BCR/abl tyrosine kinase as potential
      mediators of oncogenic signaling. It was recently found that the 120 kDa protein
      product of the c-cbl proto-oncogene is highly tyrosine phosphorylated and
      associates with BCR/abl in transformed hematopoietic cells. We have characterized
      further cbl's involvement in BCR/abl mediated tumorigenesis using growth factor
      independent BCR/abl transformed BaF3 cells. Our experiments show that, in
      contrast to other cell types, the in vivo interaction of cbl with GRB2 and p85 is
      significantly enhanced in BCR/abl transformed BaF3 cells and that tyrosine
      phosphorylation of cbl leads to a direct interaction with GRB2, p85 and abl SH2
      domains. A 14-fold increase in cbl associated PI 3-kinase activity in BCR/abl
      transformed cells suggests that the binding of p85 SH2 domains to tyrosine
      phosphorylated cbl may contribute to PI 3-kinase activation. Domain analysis
      studies indicate that both SH3 domains of GRB2 bind to the proline rich region of
      cbl in quiescent BaF3 cells, whereas GRB2 SH2 domain interacts with a non
      contiguous sequence of cbl in transformed cells. Although the interaction of cbl
      with GRB2 in transformed cells was facilitated by binding of GRB2 to BCR/abl,
      phosphorylation of cbl and its interaction with p190 BCR/abl remained unaltered
      in BaF3 cells transformed by p190Y177F BCR/abl mutant which is unable to bind
      GRB2. The current information and the data presented here suggest that, although
      cbl lacks src homology domains, it represents a novel intermediate protein which,
      by interaction with key SH-containing adaptor proteins, may participate in
      regulation of the Ras and PI 3-kinase pathways in BCR/abl transformed
      hematopoietic cells.

PMID- 9174059
TI  - Transcription factor AP2 is required for expression of the rat transforming
      growth factor-alpha gene.
AB  - DNase I footprinting of the rat TGF alpha promoter in the presence of crude cell
      nuclear extract revealed three sites of protein-DNA interaction (Fp-A, Fp-B, Fp
      C) in the region from -222 to +73. Mutation of specific sites within the Fp-A and
      Fp-B regions reduced expression of a TGF alpha promoter-reporter gene (TGF
      alphaLUC) from 50-90% in transiently transfected CHO cells, indicating the
      importance of protein/DNA interactions at these sites. Since Fp-A contained a
      perfect AP2 consensus sequence (5'-GCCNNNGGC-3') as its center, we investigated
      the possibility that AP2 binding is important for TGF alpha promoter activity. A
      double-stranded oligonucleotide spanning Fp-A displayed a distinct mobility shift
      in the presence of nuclear extract that was inhibited by an excess of known
      functional AP2-binding sequence. Moreover, a similar mobility shift occurred in
      the presence of purified AP2 protein, and the further addition of AP2 antibody
      produced a supershifted complex. More refined DNase I footprinting of a smaller,
      oligonucleotide probe in the presence of purified AP2 protein revealed a
      protected region that included the putative AP2 binding site. Additionally, co
      transfection of an AP2 expression vector increased TGF alphaLUC expression 25
      fold in Drosophila Schneider cells. These various findings corroborate a role for
      AP2 in TGF alpha promoter activity. The Fp-B region contains a T5 motif that has
      been previously suggested to function as an atypical TATA box. An Fp-B
      oligonucleotide displayed a specific gel mobility shift in the presence of a TATA
      binding protein (TBP)-TFIIA complex, and the further addition of TBP antibody
      produced a supershift. These results confirm that protein binding within Fp-B is
      functionally important, and they also indicate that the T5 motif functions as a
      TBP binding site.

PMID- 9174060
TI  - EGF receptor binding and transformation by v-cbl is ablated by the introduction
      of a loss-of-function mutation from the Caenorhabditis elegans sli-1 gene.
AB  - The 120 kD product of the c-cbl oncogene is rapidly tyrosine phosphorylated and
      recruited to the EGF receptor following ligand binding. Cbl's oncogenic potential
      is activated by a large carboxy-terminal truncation that generated v-cbl and
      removes the Ring finger and proline-rich SH3-binding domains. Here we show that
      this truncation reveals a novel and highly conserved domain that can interact
      directly with the EGF receptor in a phosphorylation dependent manner. Furthermore
      we demonstrate that the v-cbl domain is not utilized by c-cbl for recruitment to
      the receptor since this binding property is not evident in c-cbl constructs with
      proline domain deletions, and it is only revealed following deletion of the Ring
      finger. We also analyse a loss-of-function mutation from the C. elegans
      homologue, sli-1, and show that the corresponding mutation in v-cbl ablates
      transformation and EGF receptor association. Thus our findings provide further
      evidence that v-cbl possesses a novel and evolutionarily conserved
      phosphotyrosine binding domain and that the dual capability of EGF receptor
      binding by cbl involves two distinct mechanisms. In addition these findings raise
      the possibility that v-cbl may transform by competing with c-cbl for
      phosphorylated binding sites on activated receptor complexes.

PMID- 9174061
TI  - EAAT4, a glutamate transporter with properties of a chloride channel, is
      predominantly localized in Purkinje cell dendrites, and forms parasagittal
      compartments in rat cerebellum.
AB  - Glutamate transporters play a pivotal role in terminating glutamatergic
      transmission by eliminating glutamate from the synaptic cleft. Four different
      glutamate transporter cDNAs have been isolated thus far, and their tissue
      distribution has been investigated using northern blot and immunohistochemical
      analysis. We raised site-directed antisera against a synthetic oligopeptide
      corresponding to the C-terminal of EAAT4, a recently cloned human glutamate
      transporter, and investigated the distribution of EAAT4 in rat cerebellum.
      Western blot analysis demonstrated that the affinity-purified antiserum SAE4
      recognized specifically a single band (about 62 kDa) in the rat cerebellum,
      cerebrum and spinal cord. The SAE4-immunoreactivity was localized predominantly
      in the dendritic spines and distal dendrites of Purkinje cells. The intensity of
      the immunoreactivity was uneven among Purkinje cells, forming parasagittal
      compartments. Since EAAT4 also has the properties of a glutamate-gated chloride
      channel, it should be able to modulate the transmission at the parallel fiber
      Purkinje cell synapses.

PMID- 9174062
TI  - Differences in the mode of stimulation of cultured rat sympathetic neurons
      between ATP and UDP.
AB  - Postganglionic sympathetic neurons possess at least two excitatory receptors for
      nucleotides: P2X-purinoceptors and separate receptors for uracil nucleotides. In
      cultured neurons from rat superior cervical ganglia (SCG), both receptors, when
      activated, induce release of noradrenaline. Here we describe marked differences
      between the responses of cultured neurons from rat thoracolumbal paravertebral
      ganglia to ATP and UDP. ATP elicited release of previously taken up
      [3H]noradrenaline, induced an inward current, and increased the intra-axonal free
      calcium level, over the same range of micromolar concentrations. UDP was more
      potent than ATP in releasing [3H]noradrenaline but induced an inward current only
      at a concentration of 1 mM and caused much smaller increases in intraaxonal free
      calcium. The mechanism of action of ATP presumably consists of P2X-purinoceptor
      activation followed by depolarization, calcium entry through voltage-sensitive
      channels and exocytosis. The mode of action of UDP is different. It probably
      activates a G-protein-coupled pyrimidinoceptor. The pyrimidinoceptor then
      possibly mediates mobilization of intracellular calcium close to the sites of
      transmitter release and in addition an increase in the calcium sensitivity of the
      exocytotic apparatus.

PMID- 9174063
TI  - The projection from the striatum to the nucleus basalis in the rat: an electron
      microscopic study.
AB  - Previous studies have shown that the striatum provides synaptic inputs to the
      globus pallidus and entopeduncular nucleus in which GABA is co-localized with the
      peptides enkephalin and substance P. The aim of this study in the rat was to
      determine whether the striatal projections also make synaptic contact with the
      cholinergic neurons of the nucleus basalis, which lie near to the pallidal areas
      in the rat brain. The anterograde tracer biocytin was injected into different
      parts of the striatum, and brain sections were stained for biocytin and choline
      acetyltransferase immunoreactivity by using a dual colour method. Terminals
      labelled with biocytin by anterograde transport and which made synaptic contact
      with choline acetyltransferase-positive soma and dendrites were identified by
      light-electron microscopic correlation methods. In the cases where the biocytin
      injections had been made in the dorsal or lateral striatum, biocytin-labelled
      terminals made synaptic contact with cholinergic cells in the region between the
      main termination zones in the globus pallidus and the entopeduncular nucleus. In
      the cases where the injections had been made in the ventromedial and posterior
      striatum, there was greater overlap between choline acetyltransferase-positive
      structures and biocytin-labelled terminals in the main termination zones in the
      globus pallidus or entopeduncular nucleus, but relatively few of these terminals
      made synaptic contacts on to the cholinergic neurons. The results therefore
      indicate that the cholinergic nucleus basalis cells receive a relatively sparse
      synaptic input from all parts of the striatum. It has recently been shown that
      the cholinergic cells of the nucleus basalis selectively express high levels of
      substance P and opioid receptor messenger RNAs, while the non-cholinergic
      pallidal cells have much higher levels of GABA(A) receptor subunit messenger
      RNAs. It is concluded that the cholinergic neurons of the nucleus basalis in the
      rat may be selectively responsive to the peptidergic components of the striatal
      outputs, and that they are most likely to be influenced by both the limbic and
      sensorimotor parts of the striatum.

PMID- 9174064
TI  - Neurons are generated in confluent astroglial cultures of rat neonatal neocortex.
AB  - Cells of the telencephalon are generated in specific proliferative zones from
      which neuronal and glial precursors migrate to their destinations. Recent
      evidence indicates that some precursors do not turn into differentiated cells but
      keep their ability to proliferate. Here, we report that neurons can originate in
      primary cultures of astroglial cells prepared from neocortex of newborn rats. The
      first neuronal cells appeared shortly before confluence, when a glial monolayer
      was being formed. After confluence, these still undifferentiated cells increased
      in number. Later, they became immunohistochemically positive for the neuron
      specific marker microtubule-associated protein 2a,b. They also contained
      neurofilament-L protein as well as the specific messenger RNA coding for
      neurofilament-H. The observation that they took up bromo-deoxyuridine indicated
      that they synthesized DNA, i.e. they proliferated. When Dulbecco's modified
      essential medium was substituted with fetal calf serum, the appearance of neurons
      depended on the seeding density of the dispersed cells. This was no longer the
      case, when the cultures were maintained in Dulbecco's modified essential
      medium/F12 medium to which transferrin, insulin and selenium chloride had been
      added. It is concluded that neuronal precursors can survive in primary astroglial
      cultures. After confluence of the astroglial cells the precursors proliferate if
      appropriate conditions are present. Our observation provides a new model for the
      investigation of cultured neurons and neuronal-glial interactions.

PMID- 9174065
TI  - Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal
      dopaminergic neurons by endogenous kynurenic acid.
AB  - Endogenous excitotoxins have been implicated in the degeneration of dopaminergic
      neurons in the substantia nigra compacta of patients with Parkinson's disease.
      One such agent quinolinic acid is an endogenous excitatory amino acid receptor
      agonist. This study examined whether an increased level of endogenous kynurenic
      acid, an excitatory amino acid receptor antagonist, can protect nigrostriatal
      dopamine neurons against quinolinic acid-induced excitotoxic damage. Nigral
      infusion of quinolinic acid (60 nmoles) or N-methyl-D- aspartate (15 nmoles)
      produced a significant depletion in striatal tyrosine hydroxylase activity, a
      biochemical marker for dopaminergic neurons. Three hours following the
      intraventricular infusion of nicotinylalanine (5.6 nmoles), an agent that
      inhibits kynureninase and kynurenine hydroxylase activity, when combined with
      kynurenine (450 mg/kg i.p.), the precursor of kynurenic acid, and probenecid (200
      mg/kg i.p.), an inhibitor of organic acid transport, the kynurenic acid in the
      whole brain and substantia nigra was increased 3.3-fold and 1.5-fold respectively
      when compared to rats that received saline, probenecid and kynurenine. This
      elevation in endogenous kynurenic acid prevented the quinolinic acid-induced
      reduction in striatal tyrosine hydroxylase. However, 9 h following the
      administration of nicotinylalanine with kynurenine and probenecid, a time when
      whole brain kynurenic acid levels had decreased 12-fold, quinolinic acid
      injections produced a significant depletion in striatal tyrosine hydroxylase.
      Intranigral infusion of quinolinic acid in rats that received saline with
      kynurenine and probenecid resulted in a significant depletion of ipsilateral
      striatal tyrosine hydroxylase. Administration of nicotinylalanine in combination
      with kynurenine and probenecid also blocked N-methyl-D-aspartate-induced
      depletion of tyrosine hydroxylase. Tyrosine hydroxylase immunohistochemical
      assessment of the substantia nigra confirmed quinolinic acid-induced neuronal
      cell loss and the ability of nicotinylalanine in combination with kynurenine and
      probenecid to protect neurons from quinolinic acid-induced toxicity. The present
      study demonstrates that increases in endogenous kynurenic acid can prevent the
      loss of nigrostriatal dopaminergic neurons resulting from a focal infusion of
      quinolinic acid or N-methyl-D-aspartate. The strategy of neuronal protection by
      increasing the brain kynurenic acid may be useful in retarding cell loss in
      Parkinson's disease and other neurodegenerative diseases where excitotoxic
      mechanisms have been implicated.

PMID- 9174066
TI  - Co-localization of the D1 dopamine receptor in a subset of DARPP-32-containing
      neurons in rat caudate-putamen.
AB  - DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, apparent molecular
      weight of 32,000) is part of the D1 dopamine receptor signal transduction
      cascade. Both the D1 receptor and DARPP-32 are found in the caudate putamen, but
      it is not known if they co-localize in the medium-sized spiny neurons. In the
      present study, double-labelling immunocytochemistry was used to simultaneously
      localize the D1 receptor and DARPP-32 in the rat caudate-putamen. The neuropil
      was heavily and uniformly immunoreactive for both the D1 receptor and DARPP-32.
      All cell bodies immunopositive for the D1 receptor were immunopositive for DARPP
      32. The D1 receptor was not detectable, however, in nearly half of the DARPP-32
      containing cell bodies. DARPP-32 is present in striatopallidal and striatonigral
      projections. The D1 receptor co-localized with DARPP-32 in fibres of the
      entopeduncular nucleus and the pars reticulata of the substantia nigra. In the
      globus pallidus, however, D1 receptor immunoreactivity was barely detectable,
      while DARPP-32 immunolabelling of axons and axon terminals was intense. These
      data suggest that the striatal somata containing both the D1 receptor and DARPP
      32 project to the entopeduncular nucleus and substantia nigra, whereas somata
      containing only DARPP-32 immunoreactivity project to the globus pallidus. Thus,
      the differences in expression of the D1 receptor and of DARPP-32 within striatal
      cell bodies are likely reflected in their projections. The co-localization of the
      D1 receptor and DARPP-32 is consistent with the known regulation of DARPP-32
      phosphorylation by D1 receptor activation. The demonstration of a large
      population of striatal neurons that contain DARPP-32 but apparently do not
      contain D1 receptors substantiates the premise that these cells have an
      alternative signal transduction pathway. Subsequent studies are needed to search
      for a signal transduction pathway for these neurons analogous to the dopamine D1
      receptor pathway.

PMID- 9174067
TI  - Differential regulation of dopamine receptors after chronic typical and atypical
      antipsychotic drug treatment.
AB  - Changes in dopamine receptor subtype binding in different brain regions were
      examined after 28 days treatment of rats with haloperidol, raclopride, clozapine
      or SCH23390 using in vitro receptor autoradiography. [3H]7-hydroxy-N,N-di-n
      propyl-2-aminotetralin binding to dopamine D3 receptors was not changed in any
      brain region by any of the drug treatments. [3H]SCH23390 was only increased by
      chronic SCH23390 treatment. Haloperidol significantly increased [3H]nemonapride
      and [3H]spiperone binding to dopamine D2-like receptors in the caudate putamen.
      In contrast, haloperidol caused a small, significant increase in [3H]raclopride
      binding in the lateral caudate putamen only. Raclopride also elevated, but to a
      lesser extent [3H]nemonapride and [3H]spiperone binding in caudate putamen,
      whereas it did not affect [3H]raclopride binding. Clozapine did not significantly
      change D2-like striatal binding of [3H]nemonaipride, [3H]spiperone or
      [3H]raclopride. The differences in radioligand binding suggest that
      [3H]nemonapride and [3H]spiperone may be binding to additional subsets of
      dopamine D2-like receptors (including D4-like receptors) that are not recognized
      by [3H]raclopride, which has high affinity for D2 and D3 receptors only.
      Quantification of [3H]nemonapride or [3H]spiperone binding in the presence of 300
      nM raclopride (to block D2 and D3 receptors) revealed that haloperidol,
      raclopride and clozapine up-regulated D4-like receptors in the caudate putamen
      using either radioligand. These results suggest that D4-like receptors may be a
      common site of action of both typical and atypical antipsychotics.

PMID- 9174068
TI  - Effects of pilocarpine and kainate-induced seizures on N-methyl-D-aspartate
      receptor gene expression in the rat hippocampus.
AB  - The effects of pilocarpine- and kainate-induced seizures on N-methyl-D-aspartate
      receptor subunit-1 messenger RNA and [3H]dizocilpine maleate binding were studied
      in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures
      decreased N-methyl-D-aspartate receptor subunit-1 messenger RNA level in dentate
      gyrus at 24 and 72 h after drug injection. Both convulsants decreased the
      messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate
      being more profound. Kainate also decreased the N-methyl-D-aspartate receptor
      subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas
      pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate,
      but not pilocarpine, an increased binding of [3H]dizocilpine maleate in several
      apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the
      [3H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the
      drug injection. Pilocarpine but not kainate induced prolonged decrease in N
      methyl-D-aspartate receptor subunit-1 gene expression in dentate gyrus. However,
      at the latest time measured, kainate had the stronger effect in decreasing both
      messenger RNA N-methyl-D-aspartate receptor subunit-1 and [3H]dizocilpine maleate
      binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes
      corresponded, however, to neuronal loss and may reflect higher neurotoxic potency
      of kainate. These data point to some differences in hippocampal N-methyl-D
      aspartate receptor regulation in pilocarpine and kainate models of limbic
      seizures. Moreover, our results suggest that the N-methyl-D-aspartate receptor
      subunit-1 messenger RNA level is more susceptible to limbic seizures than is
      [3H]dizocilpine maleate binding in the rat hippocampal formation.

PMID- 9174069
TI  - Electrophysiological changes in rat hippocampal pyramidal neurons produced by
      cholecystokinin octapeptide.
AB  - Effects of cholecystokinin octapeptide (CCK-8) were investigated in CA1 pyramidal
      neurons of rat hippocampal slice cultures using the whole-cell patch-clamp
      technique. In the current-clamp mode, CCK-8 (100 nM) produced slight
      depolarizaton (2.1 +/- 0.3 mV) and reduced the amplitude of
      afterhyperpolarization following a train of spikes. CCK-8 (10 nM-1 microM)
      concentration-dependently reduced the amplitude of afterhyperpolarization. CCK-4,
      a selective agonist for CCK(B) receptors, also attenuated the amplitude of
      afterhyperpolarization. CCK-8-induced suppression was completely abolished by
      (+)L-365,260, a selective CCK(B) receptor antagonist, but not by (-)L-364,718, a
      selective CCK(A) receptor antagonist. Similarly, CCK-8 reduced the tail currents
      following a depolarizing pulse. The tail currents were characterized as Ca2+
      activated K+ currents. When neurons were held at a holding potential of -40 mV,
      CCK-8 elicited inward currents with a reduction of membrane conductance. This
      current had a relatively linear current voltage relationship and was reversed in
      polarity at membrane potentials close to the K+ equilibrium potential, suggesting
      that CCK-8 decreases leak K+ currents. Moreover, voltage-activated Ca2+ currents
      were partially blocked by CCK-8, and this effect was enhanced by intracellular
      application of GTPgammaS (300 microM) or a protein phosphatase inhibitor, okadaic
      acid (100 nM), and attenuated by GDPbetaS (300 microM) or a protein kinase
      inhibitor, staurosporin (400 nM). In acutely-prepared hippocampal slices from
      neonatal rats, CCK-8 also depolarized CA1 pyramidal neurons and suppressed
      afterhyperpolarization following a train of action potentials. These results
      indicate that CCK-8 increases neuronal excitability by suppressing leak K+
      currents and Ca2+-activated K+ currents in CA1 pyramidal neurons of the
      hippocampus through activation of CCK(B) receptors.

PMID- 9174070
TI  - Effects of serotonin through serotonin1A and serotonin4 receptors on inhibition
      in the guinea-pig dentate gyrus in vitro.
AB  - The role of serotonin1A and serotonin4 receptors in the modulation of synaptic
      inhibition in the dentate gyrus of guinea-pig hippocampal slices was studied. The
      effects of serotonin (5-hydroxytryptamine) on hilar neurons and on inhibitory
      postsynaptic potentials in granule cells were compared using intracellular
      recording in the presence of glutamatergic receptor antagonists. On the basis of
      electrophysiological properties hilar neurons were classified as type I neurons
      (presumably inhibitory) and type II neurons (presumably excitatory). Serotonin
      hyperpolarized a proportion of type I hilar neurons (60%) and decreased their
      input resistance through activation of a K+-conductance. This effect was mediated
      by serotonin1A receptors since it was mimicked by the selective serotonin1A
      receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and blocked
      by the selective serotonin1A receptor antagonist (+) WAY 100135. In some type I
      hilar neurons (40%) neither serotonin nor (+/-)-8-hydroxydipropylaminotetralin
      hydrobromide induced a membrane hyperpolarization. Instead, serotonin induced an
      excitatory response, depolarizing the cells and blocking the slow
      afterhyperpolarization. Similar effects were seen in all hilar neurons after
      blockade of serotonin1A receptors. They were mimicked by the serotonin4 receptor
      agonist zacopride. Serotonin induced either decreases or increases in the
      frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic
      potentials in granule cells via activation of serotonin1A and of serotonin4
      receptors, respectively. 4-aminopyridine-evoked GABA(B) receptor-mediated
      inhibitory postsynaptic potentials were inhibited by serotonin via activation of
      serotonin1A receptors. However, after blockade of serotonin1A receptors,
      serotonin increased the frequency of GABA(B)-inhibitory postsynaptic potentials
      through the activation of serotonin4 receptors. We conclude that a proportion of
      inhibitory neurons in the dentate area does not express serotonin1A receptors and
      is excited by serotonin. Other inhibitory neurons express serotonin1A receptors
      and are inhibited by serotonin.

PMID- 9174071
TI  - Integration of chemosensory and hormonal cues is essential for sexual behaviour
      in the male Syrian hamster: role of the medial amygdaloid nucleus.
AB  - Mating behaviour in the male hamster requires chemosensory and hormonal cues, and
      copulation is abolished if either signal is interrupted. In addition, the
      integration of chemosensory stimuli with steroid signals is essential for mating.
      In castrated male hamsters, implantation ofa testosterone-filled cannula in the
      preoptic area stimulates mating behaviour. However, removal of the ipsilateral
      olfactory bulb prevents steroid facilitation of sexual activity. The present
      studies determined if the integration of chemosensory and hormonal cues necessary
      for mating behaviour is distributed within steroid-sensitive nuclei in the brain,
      or is restricted to the preoptic area. Specifically, the hypothesis was tested
      that the medial amygdala is capable of odour and hormone integration. Castrated
      male hamsters received an intracerebral implant of testosterone in the medial
      amygdala combined with removal of a single olfactory bulb, ipsilateral or
      contralateral to the implant. Mating behaviour did not increase after implant
      surgery and bulbectomy in either ipsilateral or contralateral bulbectomized
      males. In a second study, males were bulbectomized three weeks after implant
      surgery, to demonstrate the ability of testosterone in the medial amygdala to
      stimulate male sexual behaviour, and the loss of behaviour following bulbectomy.
      The results confirm that integration of odour and steroid cues is essential for
      mating in the male hamster. Moreover, the medial amygdaloid nucleus contributes
      to chemosensory and hormonal integration. However, compared with steroid
      stimulation in the preoptic area, the behavioural effects of testosterone in the
      medial amygdaloid nucleus are more sensitive to manipulations of the olfactory
      system, suggesting that the amygdala requires bilateral chemosensory input.

PMID- 9174072
TI  - Axotomized septal cholinergic neurons rescued by nerve growth factor or
      neurotrophin-4/5 fail to express the inducible transcription factor c-Jun.
AB  - The inducible transcription factor c-Jun increases in neurons in response to
      axotomy by unknown mechanisms, and it has been postulated that c-Jun may regulate
      genes involved in promoting either degeneration or regeneration of axotomized
      neurons. In this report, we investigated the effect of daily or twice daily
      intraventricular administration of the neurotrophins nerve growth factor or
      neurotrophin-4/5 on the decrease in choline acetyltransferase expression and the
      increase in c-Jun expression in rat medial septum/diagonal band neurons three,
      seven and 14 days following unilateral, complete, fornix fimbria lesion. We also
      examined whether medial septum/diagonal band neurons might die by apoptosis
      within two weeks of fornix fimbria lesion using terminal deoxynucleotidyl
      transferase-mediated dUTP biotin nick end labelling. Our results show that both
      nerve growth factor and neurotrophin-4/5 maintain the phenotype of basal
      forebrain cholinergic neurons following axotomy. Furthermore, using double
      labelling immunofluorescence, we found that while c-Jun was expressed in
      cholinergic neurons in control-treated rats seven days following fornix fimbria
      lesion, cholinergic neurons rescued by either nerve growth factor or neurotrophin
      4/5 in neurotrophin-treated rats failed to express c-Jun. At no time-point
      (three, seven or 14 days post-axotomy) did any neurons in the medial
      septum/diagonal band stain positive for terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labelling, suggesting that medial septum/diagonal
      band neurons do not undergo apoptosis within the first two weeks following
      axotomy at the time-points observed by us. Therefore, these results show that
      both nerve growth factor and neurotrophin-4/5 rescue the phenotype of axotomized
      cholinergic neurons and that these rescued neurons fail to express c-Jun in
      response to axotomy. In addition, since neither nerve growth factor nor
      neurotrophin-4/5 induced c-Jun in medial septum/diagonal band cholinergic
      neurons, it seems unlikely that the neurotrophic effects of nerve growth factor
      and neurotrophin-4/5 on cholinergic neurons are mediated via c-Jun expression.
      Furthermore, since axotomy failed to increase terminal deoxynucleotidyl
      transferase-mediated dUTP biotin nick end labelling in septal neurons, it appears
      unlikely that c-Jun expression in these axotomized neurons is related to neuronal
      degeneration via apoptosis.

PMID- 9174073
TI  - Thalamic-projecting preprocholecystokinin messenger RNA-expressing neurons in the
      dorsal column nuclei of the rat.
AB  - This study aimed at investigating the expression of preprocholecystokinin
      messenger RNA among thalamic-projecting neurons in the dorsal column nuclei of
      the rat. Thalamic-projecting neurons were identified by injection of cholera
      toxin subunit b into the ventroposterolateral nucleus. Following
      immunohistochemical detection of retrogradely transported tracer substance, the
      expression of preprocholecystokinin messenger RNA in the projection neurons of
      the dorsal column nuclei was detected by in situ hybridization, using
      autoradiographic visualization of a 35S-labeled RNA probe complementary to
      preprocholecystokinin messenger RNA. Many preprocholecystokinin-expressing
      neurons were seen in the dorsal column nuclei. A large proportion of these
      neurons were also labeled with cholera toxin. The double-labeled neurons, as well
      as neurons single-labeled with preprocholecystokinin messenger RNA or cholera
      toxin, were preferentially found within the middle region of the dorsal column
      nuclei, located just caudal to the obex. These findings demonstrate that neurons
      in the dorsal column nuclei express preprocholecystokinin messenger RNA, and show
      that these neurons provide a peptidergic projection from the dorsal column nuclei
      to the ventroposterolateral nucleus of the thalamus. These observations suggest
      that cholecystokinin may be involved in the transmission of somatosensory
      (tactile) information from the dorsal column nuclei to the thalamus.

PMID- 9174074
TI  - Chemical sensory deafferentation abolishes hypothalamic pituitary activation
      induced by noxious stimulation or electroacupuncture but only decreases that
      caused by immobilization stress. A c-fos study.
AB  - We have shown in previous c-fos studies that noxious stimulation or
      electroacupuncture in deeply anaesthetized rats activate the hypothalamic
      pituitary corticotrope axis in a specific way. C-fos expression was more
      pronounced in the arcuate than the paraventricular hypothalamic nuclei, and none
      occurred in the pituitary intermediate lobe. The absence of the usual autonomic
      responses to psychological stress, such as tachycardia or blood pressure
      elevation, suggested a specific action of the somatosensory input on the
      hypothalamic pituitary axis. To prove this hypothesis, c-fos expression was
      examined in the paraventricular, arcuate and other hypothalamic nuclei, the
      pituitary gland, and the A1 and A2 medullary catecholaminergic cell groups of
      animals deprived of nociceptive primary afferent input by neonatal capsaicin.
      After noxious stimulation or electroacupuncture, no c-fos enhancement occurred in
      any of those sites in capsaicin-treated animals, and there was no increased
      plasma release of adrenocorticotropic hormone. In contrast, the hypothalamic
      pituitary c-fos activation provoked by immobilization stress though markedly
      decreased, was not abolished by capsaicin, whereas plasma release of
      adrenocorticotropic hormone remained undiminished. These findings suggest that
      noxious stimulation or electroacupuncture act on the hypothalamic pituitary
      corticotrope axis through an exclusively physical effect depending on the noxious
      signal elicited in the somatosensory pathway. They also demonstrate the
      occurrence of a minor somatosensory physical component after forced
      immobilization, acting on the hypothalamic pituitary axis probably together with
      the prevalent component of emotional arousal elicited by this form of stress.

PMID- 9174075
TI  - Neuronal activation in the forebrain following electrical stimulation of the
      cuneiform nucleus in the rat: hypothalamic expression of c-fos and NGFI-A
      messenger RNA.
AB  - Forebrain neuronal connections associated with the cardiovascular response to
      unilateral, low-intensity, electrical stimulation of the mesencephalic cuneiform
      nucleus were examined in the halothane-anesthetized and paralysed rat by in situ
      hybridization histochemistry using specific 35S-labelled oligonucleotides for
      detection of c-fos and nerve growth factor inducible-A gene (NGFI-A) messenger
      RNAs. Stimulation of the cuneiform nucleus led to increases in mean arterial
      pressure and heart rate, whereas no cardiovascular response was observed in
      animals stimulated in the inferior colliculus or in sham-operated animals [see
      concurrent mid- and hindbrain study [Lam W. et al. (1996) Neuroscience 71, 193
      211]. Cuneiform nucleus stimulation was associated with increased c-fos and NGFI
      A messenger RNA levels bilaterally in the ventromedial, dorsomedial and
      lateroanterior hypothalamic nuclei, lateral and anterior hypothalamic areas, and
      ipsilaterally in the medial amygdaloid nucleus, at levels significantly greater
      than those in inferior colliculus-stimulated, sham-operated and naive, unoperated
      animals. C-fos, but not NGFI-A, messenger RNA expression was increased
      bilaterally in the piriform cortex and subparafascicular thalamic nucleus. These
      results are consistent with the existence of direct and indirect projections
      between the cuneiform nucleus and the aforementioned activated areas, the
      functions of which may include the control of reproduction and metabolism, as
      well as cardiovascular regulation. The ipsilateral nature of responses in certain
      brain areas may be explained by the absence of decussating pathways and/or the
      presence of multisynaptic connections which attenuate bilateral signal
      transmission. The existence of structures that are known to receive afferent
      projections from the cuneiform nucleus, but that were not activated, may be
      explained by synaptic depolarization not reaching the threshold for immediate
      early gene expression or by a net inhibitory effect on innervated neurons.
      Characterization of these activated forebrain regions using other compatible
      labelling techniques should further elucidate the mechanisms by which these
      central nervous system structures are integrated in the response to stimulation
      of the cuneiform nucleus.

PMID- 9174076
TI  - Elicitation and reduction of fear: behavioural and neuroendocrine indices and
      brain induction of the immediate-early gene c-fos.
AB  - The elicitation and reduction of fear were indexed with fear-potentiated startle
      and corticosterone release and induction of the immediate-early gene c-fos as a
      marker of neural activity in male Sprague-Dawley rats. Conditioning consisted of
      pairing one stimulus with footshock, which was withheld when the conditioned
      stimulus was preceded by a different modality stimulus, the conditioned
      inhibitor. On the test day, approximately 60% of the rats were used for c-fos in
      situ hybridization, and were presented with either the conditioned stimulus
      alone, the conditioned inhibitor alone, a compound of the two stimuli, or no
      stimuli, and killed 30 min following the presentation of 10 such stimuli. The
      remaining rats were tested with the fear-potentiated startle paradigm. Rats
      displayed reliable fear-potentiated startle and corticosterone release to the
      conditioned stimulus, and both measures were reduced when the conditioned
      stimulus was preceded by the conditioned inhibitor. The ventral bed nucleus of
      the stria terminalis, septohypothalamic nucleus, some tegmental nuclei, and the
      locus coeruleus had particularly high c-fos induction in rats that received the
      conditioned inhibitor, providing one of the first functional indication that
      these nuclei might be important in behavioural or endocrine inhibition.
      Conditioning specific c-fos induction in the three groups that received a
      stimulus on the test day was observed in many hypothalamic areas, the medial
      geniculate body and the central gray, structures previously involved in fear and
      anxiety. The cingulate, infralimbic and perirhinal cortex, nucleus accumbens,
      lateral septum, dorsal endopiriform nucleus, and ventral tegmental area had
      higher c-fos induction in rats presented with the fearful conditioned stimulus,
      confirming previous studies. The amygdala and hippocampus of conditioned rats did
      not show higher c-fos induction than in rats repeatedly exposed to the context.
      Many regions displayed c-fos messenger RNA induction in the control condition,
      suggesting that processes other than fear and anxiety participate in c-fos
      induction.

PMID- 9174077
TI  - N-methyl-D-aspartate receptors containing the NR2D subunit in the retina are
      selectively expressed in rod bipolar cells.
AB  - N-methyl-D-aspartate receptor subunit messenger RNAs are widely expressed in the
      retina and several types of second and third order neurons are responsive to N
      methyl-D-aspartate. Functional N-methyl-D-aspartate receptors are assembled from
      the NR1 subunit with at least one of the four NR2 subunit variants (NR2A-2D). We
      have analysed immunohistochemically the cellular distribution of N-methyl-D
      aspartate receptors containing the NR2D subunit in the rat and rabbit retina.
      Using a subunit-specific NR2D antiserum, exclusively bipolar cells with somata
      localized close to the outer plexiform layer were labelled in both species. The
      axons were immunoreactive and arborized in the innermost inner plexiform layer.
      The morphology and localization of these cells, which were much more numerous in
      rat than in rabbit, suggested that they are rod bipolar cells. This was confirmed
      in both species by co-localization of the NR2D subunit immunoreactivity with
      protein kinase C-alpha, a selective marker for rod bipolar cells. At the
      subcellular level, a distinct polarization in the distribution of NR2D
      immunoreactivity was demonstrated by confocal laser scanning microscopy: staining
      was moderate in dendrites arborizing within the outer plexiform layer, intense at
      that pole of the soma facing the outer plexiform layer, and low in the portion of
      the soma embedded in the inner nuclear layer. Proximal axonal segments and axonal
      end-feet in the inner plexiform layer displayed the strongest NR2D subunit
      immunoreactivity. The axonal staining suggests that neurotransmission of the rod
      bipolar cells is modulated within the inner plexiform layer by N-methyl-D
      aspartate receptors containing the NR2D subunit.

PMID- 9174078
TI  - Galanin messenger RNA during postnatal development of the rat brain: expression
      patterns in Purkinje cells differentiate anterior and posterior lobes of
      cerebellum.
AB  - Following our initial mapping of preprogalanin messenger RNA in adult brain and
      its presence in a subpopulation of cerebellar Purkinje neurons [Ryan M. C. and
      Gundlach A. C. (1996) Neuroscience 70, 709-728], the present study examined the
      ontogenic expression of preprogalanin messenger RNA in the postnatal rat brain
      focussing on the Purkinje cells of the cerebellar cortex. Using in situ
      hybridization histochemistry, preprogalanin messenger RNA was detected in the
      developing forebrain and hindbrain from postnatal day 4 to day 60 (adult). On
      postnatal day 4 very light hybridization signal (labelling) was observed in cells
      of a number of nuclei including the central amygdaloid nucleus, the medial
      preoptic area, paraventricular nucleus and dorsomedial hypothalamic nucleus of
      the forebrain while lightly-labelled cells were detected in neurons of the
      nucleus of the solitary tract and locus coeruleus of the hindbrain. Hybridization
      signal was not apparent in other nuclei until later, with positively-labelled
      neurons first apparent in the dorsal cochlear nucleus at postnatal day 21. The
      abundance of preprogalanin messenger RNA-positive neurons and the intensity of
      the hybridization signal increased, in most regions, until postnatal day 28 when
      labelling resembled that of the mature rat. Preprogalanin messenger RNA was first
      detected in the cerebellum on postnatal day 10 only in Purkinje cells of lobule
      10 of the posterior vermis and increased in distribution throughout Purkinje cell
      layers of the entire cerebellar cortex by postnatal day 13. The intensity of
      hybridization signal in Purkinje cells varied between lobules, with Purkinje
      cells in lobule 10 displaying a moderate to heavy degree of labelling, while
      lobules 6-9 and the more posterior lobules of the hemisphere including crus 2 of
      the ansiform lobule, the paramedian lobule and the copula pyramis, displayed only
      light labelling. The intensity of labelling in the anterior vermis and the
      remaining lobules of the hemisphere including crus 1 of the ansiform lobule, the
      simple lobule, the paraflocculus and the flocculus, was homogeneously weak. By
      postnatal day 21, Purkinje cell labelling reached maximum intensity in all
      lobules. Regional differences were still apparent, however, with labelling in the
      posterior vermis and hemisphere ranging from moderate to heavy, with only light
      to moderate labelling detected in the anterior vermis. The intensity of labelling
      in the posterior vermis and most lobules of the hemisphere was similar from
      postnatal day 21 to adulthood, while, in the anterior vermis, crus 1 of the
      ansiform lobule and the simple lobule, the intensity of hybridization decreased
      slightly by postnatal day 28 and was completely absent in Purkinje cells of the
      adult rat. Differential expression of preprogalanin messenger RNA in Purkinje
      cells of the developing rat cerebellum and transient expression in certain
      lobules suggests that galanin gene products may have a role in both the
      developing and mature rat brain and that galanin gene expression may represent a
      useful marker for differentiating the anterior and posterior cerebellar lobes.

PMID- 9174079
TI  - Involvement of three glutamate receptor epsilon subunits in the formation of N
      methyl-D-aspartate receptors mediating excitotoxicity in primary cultures of
      mouse cerebellar granule cells.
AB  - The N-methyl-D-aspartate receptors have been implicated in neuronal plasticity
      and their overactivation leads to neurotoxicity. Molecular cloning and co
      expression of various glutamate receptor zeta and epsilon complementary DNAs
      support a heteromeric structural organization for N-methyl-D-aspartate receptors.
      In this study, we show that cerebellar granular neurons in primary culture of
      mouse express glutamate receptor zeta1 and at least three glutamate receptor
      epsilon (epsilon1, epsilon2, and epsilon3) protein subunits. In vitro, the
      temporal patterns of glutamate receptor epsilon1, epsilon2, and epsilon3 subunit
      expression depend on culture stages. By day 9, a somatic and neuritic
      immunolocalization for all N-methyl-D-aspartate subunits was clearly identified
      in most neuronal, but not glial cells. The role of particular subunits in N
      methyl-D-aspartate-mediated excitotoxicity was probed by exposing the cerebellar
      granule cells to antisense oligodeoxynucleotides generated against specific N
      methyl-D-aspartate receptor subunits. Antisense oligodeoxynucleotide treatments
      significantly down-regulated the amounts of the corresponding N-methyl-D
      aspartate subunits. The decrease in N-methyl-D-aspartate subunit protein
      correlated with a reduction in N-methyl-D-aspartate-induced calcium influx and N
      methyl-D-aspartate-mediated excitotoxicity in cerebellar cultures. In contrast,
      antisense oligodeoxynucleotide treatment failed to protect neurons from 1-methyl
      4-phenylpyridinium-induced metabolic cell toxicity. Antisense
      oligodeoxynucleotide treatment targeted at N-methyl-D-aspartate glutamate
      receptor epsilon subunits demonstrate that glutamate receptor epsilon1, epsilon2,
      and epsilon3 proteins form N-methyl-D-aspartate receptors responsible for
      neurotoxic effects on cerebellar neurons. This study provides direct evidence for
      the existence of distinct N-methyl-D-aspartate receptor subunit proteins in
      cerebellar granule cells developing in vitro that may trigger N-methyl-D
      aspartate-dependent excitotoxicity.

PMID- 9174080
TI  - Antidromic burst activity of locus coeruleus neurons during cortical spreading
      depression.
AB  - The electrical activity of locus coeruleus neurons was investigated during
      cortical spreading depression in urethane-anaesthetized rats. Cortical spreading
      depression was induced by a direct application of 1-3 M KCl solution to the
      surface of the cerebral cortex. The occurrence of cortical spreading depression
      was assessed by recording negative d.c. shifts and in some experiments by
      monitoring the extracellular potassium concentrations. The mean spontaneous
      firing rate of locus coeruleus neurons was significantly reduced during cortical
      spreading depression. Approximately 60% of locus coeruleus neurons recorded
      during cortical spreading depression revealed anomalous burst activity consisting
      of multiple initial segment spikes as well as full initial segment
      somatodendritic spikes with a marked initial segment-somatodendritic break. Each
      spike of the cortical spreading depression-related burst activity occurred at
      intervals ranging from 15.0 ms to 90.1 ms (34.9 +/- 0.5 ms). The burst activity
      appeared unpredictably at variable intervals in a phasic or tonic manner during
      cortical spreading depression. The cortical spreading depression-related burst
      activity of locus coeruleus neurons mimicked antidromic spikes induced by train
      stimulation of the cerebral cortex at short interspike intervals during
      iontophoretic application of GABA to locus coeruleus neurons, whereas it was
      totally different from synaptically-activated burst activity induced by tail
      pinch. The full spikes and initial segment spikes in the cortical spreading
      depression-related burst activity failed to collide with cortically elicited
      antidromic spikes, even when they appeared within the collision interval. The
      proportion of initial segment spikes in the cortical spreading depression-related
      burst activity was reduced following an increase in membrane excitability by
      iontophoretic application of glutamate, and increased during a decreased membrane
      excitability by GABA application. The antidromic burst activity of locus
      coeruleus neurons also appeared for a short time during cortical spreading
      depression prior to the occurrence of seizure waves induced by GABA antagonists,
      while the burst activity could not be observed during seizure activity. These
      results indicate that the cortical spreading depression-related burst activity
      was of antidromic origin and that the marked initial segment-somatodendritic
      break in spontaneous spikes of locus coeruleus neurons during cortical spreading
      depression was due to reduced excitability of the somatodendritic membrane. The
      cortical spreading depression-related burst activity may cause release of a large
      amount of noradrenaline in vast regions of locus coeruleus terminal fields
      through the numerous axon collaterals, thereby playing a role in functional
      changes of brain neurons related to cortical spreading depression.

PMID- 9174081
TI  - Reflex-related activation of putative pain facilitating neurons in rostral
      ventromedial medulla requires excitatory amino acid transmission.
AB  - Although the importance of the rostral ventromedial medulla in pain modulation is
      generally accepted, the recognition that it can exert both pain facilitating and
      pain inhibiting influences, and that its constituent neuronal population is
      physiologically and pharmacologically heterogeneous, is relatively recent. A
      class of neuron which may be a source of facilitating influences from the rostral
      ventromedial medulla has been identified in electrophysiological experiments.
      These neurons, termed "on-cells," are characterized by a sudden burst of activity
      beginning just before nocifensive reflexes. This burst of firing is thought to be
      a significant factor in brainstem control of nociceptive transmission under
      physiological conditions. The aim of the present study was to determine whether
      an excitatory amino acid is involved in generation of the reflex-related burst
      that defines on-cells, and more generally, to examine the role of excitatory
      amino acid neurotransmitters within the rostral ventromedial medulla of the rat.
      Iontophoretic application of the broad-spectrum excitatory amino acid receptor
      antagonist kynurenate significantly reduced the reflex-related on-cell burst,
      whereas ongoing firing was unaffected. Spontaneous activity of other medullary
      neurons was unchanged. These data demonstrate that release of an endogenous
      excitatory amino acid neurotransmitter is necessary for the activation of on
      cells that is associated with nocifensive reflexes. In contrast, these receptors
      evidently play a much less significant role in maintaining the ongoing activity
      of any cell class in the rostral ventromedial medulla in lightly anaesthetized
      rats.

PMID- 9174082
TI  - Increased sodium appetite stimulates c-fos expression in the organum vasculosum
      of the lamina terminalis.
AB  - The relation between c-fos expression in the forebrain of Lister hooded rats and
      water and NaCl intakes was examined in response to systemic injection of
      angiotensin II, desoxycorticosterone, angiotensin II and desoxycorticosterone
      together, frusemide or low sodium diet, all treatments that induce a sodium
      appetite. Angiotensin II (1 mg/kg subcutaneously) caused significant increases in
      the 1-h intakes of water and 1.8% NaCl compared to controls, the effect on water
      intake being the greater. There was a similar increase in NaCl intake after four
      days' treatment with desoxycorticosterone (20 mg pellet subcutaneously) but water
      intake was not increased. The NaCl intake of rats given angiotensin II following
      desoxycorticosterone treatment was approximately the sum of the intakes after
      angiotensin II or desoxycorticosterone alone, but the water intake was slightly
      less than after angiotensin II alone. Frusemide pretreatment (4 mg/kg
      subcutaneously) caused an NaCl intake similar to that following angiotensin II
      and desoxycorticosterone but water intake was little affected. Low dietary sodium
      also increased salt appetite, as expected. These treatments were repeated in rats
      that were not allowed to drink NaCl, after which the brains were processed for c
      fos immunocytochemistry. This showed intense staining of the subfornical organ,
      median preoptic nucleus, organum vasculosum of the laminal terminalis,
      paraventricular nucleus and supraoptic nucleus after subcutanous angiotensin II.
      Animals given angiotensin II following desoxycorticosterone pretreatment showed
      patterns of c-fos expression that did not differ from those of angiotensin II
      alone. Treatment with desoxycorticosterone alone produced intense staining in the
      organum vasculosum of the laminal terminalis and some staining in the median
      preoptic nucleus. Frusemide gave a similar pattern of staining to
      desoxycorticosterone, stimulating c-fos expression in the same regions but to a
      lesser extent. A low salt diet resulted in increased c-fos expression only in the
      organum vasculosum of the laminal terminalis. Therefore, five different
      treatments that induced increased sodium appetite evoked distinct patterns of c
      fos expression in the anteroventral region of the third ventricle of the rat
      forebrain. Since the common feature was induction of c-fos in the organum
      vasculosum of the laminal terminalis, these results suggest a key role for this
      structure in the development of increased sodium appetite.

PMID- 9174083
TI  - Repression of vasopressin gene expression by glucocorticoids in transgenic mice:
      evidence of a direct mechanism mediated by proximal 5' flanking sequence.
AB  - Glucocorticoids are known to exert multiple effects upon neuronal systems and
      neuronal gene expression but the molecular mechanisms through which these effects
      are mediated are largely undefined. In this study, a transgenic mouse model that
      expresses a bovine vasopressin transgene was used to investigate the mechanisms
      by which this neuropeptide gene is repressed by glucocorticoids. Using both
      northern analysis and a reverse transcriptase polymerase chain reaction assay,
      depletion of glucocorticoids with the 11,beta-hydroxylase inhibitor metyrapone
      was shown to result in a dexamethasone-reversed increase in ectopic adrenal
      transgene messenger RNA levels. This result shows that sequences within the
      confines of the 3.5 kb transgene are sufficient to mediate repression by
      glucocorticoids, and indicates the involvement of a type II glucocorticoid
      receptor mechanism which is independent of cellular context. Evidence for the
      involvement of cis-acting repressive elements in the proximal 5' flanking
      sequence was obtained in further studies in which bovine transgene constructs
      were shown to be negatively regulated by dexamethasone in 293 cells. The further
      demonstration that recombinant glucocorticoid receptor binds to a vasopressin
      promoter fragment in an in vitro electrophoretic mobility shift assay provided
      additional evidence of a direct mechanism of repression. Both in vitro studies
      were consistent with the presence of a glucocorticoid regulatory element within
      the region -300 to 155 of the transcription start site. The use of an in vivo
      transgenic system combined with in vitro analyses of gene promoter fragments
      enabled the characterization of the molecular mechanisms which effect
      physiological changes in vasopressin gene expression, and provided evidence of a
      direct mechanism of repression mediated by sequences within the vasopressin gene
      promoter.

PMID- 9174084
TI  - Aminopeptidase A: distribution in rat brain nuclei and increased activity in
      spontaneously hypertensive rats.
AB  - Aminopeptidase A is a membrane-bound zinc metalloprotease which cleaves
      angiotensin II into angiotensin III. Using a new specific aminopeptidase A
      inhibitor, EC33, we evaluated its enzymatic activity in several microdissected
      brain nuclei involved in the control of cardiovascular functions and in the
      pituitary. We compared this distribution with that of the angiotensin I
      converting enzyme which converts angiotensin I to angiotensin II. Aminopeptidase
      A activity was heterogenously distributed with a 150-fold difference between the
      lowest and the highest levels. The pituitary and the circumventricular organs
      were the richest source of enzyme, followed by the median eminence, the arcuate
      nucleus, the area postrema, the choroid plexus and the supraotic and
      paraventricular nuclei. We did not find any close parallel between aminopeptidase
      A and angiotensin I-converting enzyme distributions. We examined both enzymatic
      activities in brain nuclei of spontaneously hypertensive rats. Aminopeptidase A
      activity was higher in the spontaneously hypertensive rats than in age-matched
      Wistar Kyoto control rats. The difference was up to 2.5-fold in several brain
      nuclei involved in the blood pressure regulation; in contrast, no differences in
      angiotensin I-converting enzyme activity were found in the same regions. The
      close correspondence between the distribution of aminopeptidase A activity and
      angiotensin receptors and nerve terminals in the brain associated with the
      observation that aminopeptidase A activity was overactivated in the spontaneously
      hypertensive rats suggest that this enzyme may contribute, at least in part, to
      the regulation of cardiovascular functions by its ability to convert angiotensin
      II to angiotensin III.

PMID- 9174085
TI  - Strychnine blocks inhibitory postsynaptic potentials elicited in masseter
      motoneurons by sensory stimuli during carbachol-induced motor atonia.
AB  - In previous studies we reported that large-amplitude inhibitory potentials were
      elicited in masseter motoneurons by auditory stimuli (95-dB clicks) and
      stimulation of the sciatic nerve in alpha-chloralose-anesthetized cats [Kohlmeier
      K. A. et al. (1994) Soc. Neurosci. Abstr. 20, 1218; Kohlmeier K. A. et al. (1995)
      Sleep Res. 24, 9]. These potentials were always elicited during motor atonia
      induced by the pontine injection of carbachol into the nucleus pontis oralis and
      were never elicited prior to atonia. In the present report, the hyperpolarizing
      potentials that arose in response to clicks and stimulation of the sciatic nerve
      were blocked following the juxtacellular application of strychnine, a glycinergic
      antagonist. In contrast, bicuculline, a GABA(A) receptor antagonist, did not
      suppress the carbachol-dependent hyperpolarizing potentials elicited by these
      stimuli. In some motoneurons, blockade of the inhibitory potential by strychnine
      revealed a depolarizing potential. These data suggest that clicks and stimulation
      of the sciatic nerve not only elicit inhibition of motoneurons but also activate
      an excitatory drive which is masked by elicited inhibitory postsynaptic
      potentials. These findings suggest that glycine is likely to be the
      neurotransmitter that is responsible for the inhibitory postsynaptic potentials
      elicited in masseter motoneurons following the presentation of auditory and
      somatosensory stimuli during carbachol-induced motor atonia. We suggest that the
      same system that mediates glycinergically-dependent motor atonia during naturally
      occurring active sleep [Chase M. H. et al. (1989) J. Neurosci. 9, 743-751] also
      mediates the carbachol-dependent response of motoneurons to sensory stimuli.

PMID- 9174086
TI  - Release of ATP from cultured rat astrocytes elicited by glutamate receptor
      activation.
AB  - The release of ATP was studied in cultures of astrocytes derived from the brain
      hemispheres of newborn rats. There was a basal efflux of ATP, which was increased
      up to 19-fold by glutamate (300-1000 microM). N-methyl-D-aspartate (20-500
      microM), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 30-100
      microM) and kainate (20 microM). The N-methyl-D-aspartate receptor-selective
      antagonist 2-amino-5-phosphonopentanoate (100 microM) blocked the effect of N
      methyl-D-aspartate but not the effects of AMPA, kainate and glutamate. The AMPA
      receptor-selective antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(f)quinoxaline (30 microM) blocked the effect of AMPA and also of glutamate
      and N-methyl-D-aspartate, but not the effect of kainate. The kainate receptor
      selective antagonist D-glutamyl-amino-methanesulfonate (30 microM) blocked the
      effect of kainate but not of glutamate. Glutamate (1000 microM) did not increase
      the release of lactate dehydrogenase from astrocytes. Excitatory amino acids are
      known to release adenyl compounds in the brain. The present results identify one
      adenyl compound thus released, namely ATP, and identify astrocytes as one source.
      The release is brought about by activation of any of the three ionotropic
      glutamate receptor types-N-methyl-D-aspartate, AMPA and kainate receptors. AMPA
      receptors seem to mediate at least a part of the effect of glutamate itself, but
      the involvement of other receptors cannot be ruled out. ATP and its degradation
      products, such as adenosine, once released, may exert acute as well as trophic
      effects on neurons and glial cells.

PMID- 9174087
TI  - Dependence of photoreceptor glutamate release on a dihydropyridine-sensitive
      calcium channel.
AB  - A "reduced retina" preparation, consisting of the photoreceptor layer attached to
      the pigment epithelium in the eyecup, was used to study the pharmacology of the
      calcium channels controlling glutamate release by photoreceptors in Xenopus.
      Glutamate release was evoked either by dark adaptation or by superfusion with
      elevated (20 mM) potassium medium. Both darkness- and potassium-induced release
      were blocked by cadmium (200 microM). The N-type calcium channel blocker, omega
      conotoxin GVIA (500 nM), the P-type calcium channel blocker, omega-agatoxin IVA
      (20 nM), and the P- and Q-type channel blocker omega-conotoxin MVIIC (1 microM)
      had no effect on glutamate release. In contrast, the dihydropyridines, nifedipine
      (10 microM) and nitrendipine (10 microM), which affect L-type calcium channels,
      blocked both darkness- and potassium-induced release. Bay K 8644 (10 microM),
      which promotes the open state of L-type calcium channels, enhanced glutamate
      release. These results indicate that photoreceptor glutamate release is
      controlled mainly by dihydropyridine-sensitive calcium channels. A dependence of
      glutamate release on L-type calcium channels also has been reported for
      depolarizing bipolar cells of a fish retina. Thus, it appears that non
      inactivating L-type calcium channels are appropriate to mediate transmitter
      release in neurons whose physiological responses are sustained, graded
      potentials.

PMID- 9174088
TI  - Ion channels of human microglia in culture.
AB  - Macroscopic and microscopic currents have been recorded using human microglia
      isolated from fetal human brains (12-20 weeks gestation). Within a period of two
      days following plating of cells, inward K+ currents were small (mean amplitude of
      0.3 nA at -100 mV) and outward K+ currents were not observed. For periods in
      excess of five days after adherence to substrate, an inactivating outward K+
      current, sensitive to 4-aminopyridine, was expressed. A slowly rising current,
      blocked by tetraethylammonium, was also evident in a small population of human
      microglia. This current was activated with cell depolarization positive to +10 mV
      and had properties similar to those recently described for a proton current in
      mouse cells. In early adherent cells (days 1 or 2 after plating), treatment of
      microglia with interferon-gamma led to the expression of outward K+ current which
      was lacking in the absence of the treatment. In excised, inside-out patches, two
      high conductance channels were identified. A calcium-dependent K+ channel
      (unitary conductance of 106 pS with physiological levels of K+ across the patch)
      had an open probability of 0.5 with internal Ca2+ at 7 microM and the patch
      potential at 0 mV. In addition, an anion channel (unitary conductance of 280 pS)
      was transiently activated with depolarizing or hyperpolarizing steps applied from
      0 mV. Characterization of the macroscopic and unitary properties of currents in
      microglia will have relevance to a description of putative cell functions in the
      human CNS. In particular, modification of cell electrophysiological properties by
      various activating stimuli may contribute to signalling processes in CNS
      pathology.

PMID- 9174089
TI  - Caffeine reduces the efficacy of electroreceptor cell synapses: an
      electrophysiological single-unit in vivo study.
AB  - Ampullary electroreceptor organs of catfish, Ictalurus melas, were exposed
      apically to caffeine solutions at concentrations of 0, 5, 7.5, 10, and 15 mM.
      Recording sinusoidally-modulated activity of single-unit afferents reveals a dose
      dependent decrease in mean afferent activity and sensitivity. A rebound effect of
      average activity occurs after caffeine is washed out. After 25 min exposure to 15
      mM caffeine the peak of the gain curve shifts from 8 Hz to 4 Hz. The
      corresponding phase characteristic shows an increased phase lag with a maximum
      shift of 35 degrees at 20 Hz. The latency between stimulus and response increases
      from 12 to 19 ms; the recovery time after onset of the pulse decreases with 60
      ms. The most probable explanation for the recorded effects is that caffeine
      reduces the availability of intracellular Ca2+ by blocking of the inositol
      triphosphate receptors in the endoplasmic reticulum. This in turn would affect
      many intracellular properties and processes. The unavailability of Ca2+ could
      reduce the synaptic efficacy and increase latency by suppressing fusion of
      synaptic vesicles with the presynaptic membrane and by depressing vesicle
      transport. The change in frequency response corresponds in part to reduction of
      the apical membrane surface area of the receptor cells, and in part to the
      increased latency. Accumulation of glutamate-containing vesicles could account
      for the higher mean activity and modulation amplitude in the lower frequency
      range after caffeine is washed out. Caffeine might act postsynaptically by
      inducing hyperpolarization of the terminals of the primary afferents.

PMID- 9174090
TI  - Phylogenetic evidence for a new tertiary interaction in bacterial RNase P RNAs.

PMID- 9174091
TI  - Identification of the universally conserved core of ribonuclease P RNA.

PMID- 9174092
TI  - Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate
      complex by site-specific photoaffinity crosslinking.
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, and a low-resolution model of the three
      dimensional structure of the ribozyme-substrate complex has been proposed based
      on site-specific crosslinking and phylogenetic comparative data [Harris ME et
      al., 1994 EMBO J 13:3953-3963]. However, several substructures of that model were
      poorly constrained by the available data. In the present analysis, additional
      constraints between elements within the Escherichia coli RNase P RNA-pre-tRNA
      complex were determined by intra- and intermolecular crosslinking experiments.
      Circularly permuted RNase P RNAs were used to position an azidophenacyl
      photoactive crosslinking agent specifically at strategic sites within the
      ribozyme-substrate complex. Crosslink sites were mapped by primer extension and
      confirmed by analysis of the mobility of the crosslinked RNA lariats on
      denaturing acrylamide gels relative to circular and linear RNA standards.
      Crosslinked species generally retained significant catalytic activity, indicating
      that the results reflect the native ribozyme structure. The crosslinking results
      support the general configuration of the structure model and predicate new
      positions and orientations for helices that were previously poorly constrained by
      the data set. The expanded library of crosslinking constraints was used, together
      with secondary and tertiary structure identified by phylogenetic sequence
      comparisons, to refine significantly the model of RNase P RNA with bound
      substrate pre-tRNA. The crosslinking results and data from chemical-modification
      and mutational studies are discussed in the context of the current structural
      perspective on this ribozyme.

PMID- 9174093
TI  - Ribonuclease P RNA: models of the 15/16 bulge from Escherichia coli and the P15
      stem loop of Bacillus subtilis.
AB  - The Escherichia coli ribonuclease P RNA 15/16 internal bulge loop and the
      Bacillus subtilis P15 stem loop are important substrate binding sites for the CCA
      3' terminus of pre-tRNA. Models of E. coli 15/16 bulge loop and the B. subtilis
      P15 stem loop have been constructed using MC-SYM, a constraint satisfaction
      program. The models use covariation analysis data for suggesting initial base
      pairings, chemical probing, and protection/modification results to determine
      particular pairing orientations, and mutational experimental analysis data for
      tRNA-RNase P RNA contacts. The structures from E. coli and B. subtilis, although
      different in secondary structure, have similar sequence and function. Using MC
      SYM, we are able to illustrate how the 3' end of the pre-tRNA is able to interact
      with this segment of the catalytic RNase P RNA. In addition, we propose
      additional hydrogen bonding between A76 in the 3' terminus of the tRNA and the
      15/16 region of E. coli and to the loop of B. subtilis.

PMID- 9174094
TI  - Splicing of a divergent subclass of AT-AC introns requires the major spliceosomal
      snRNAs.
AB  - AT-AC introns constitute a minor class of eukaryotic pre-mRNA introns,
      characterized by 5'-AT and AC-3' boundaries, in contrast to the 5'-GT and AG-3'
      boundaries of the much more prevalent conventional introns. In addition to the AT
      AC borders, most known AT-AC introns have highly conserved 5' splice site and
      branch site sequence elements of 7-8 nt. Intron 6 of the nucleolar P120 gene and
      intron 2 of the SCN4A voltage-gated skeletal muscle sodium channel are AT-AC
      introns that have been shown recently to be processed via a unique splicing
      pathway involving several minor U snRNAs. Interestingly, intron 21 of the same
      SCN4A gene and the corresponding intron 25 of the SCN5A cardiac muscle sodium
      channel gene also have 5'-AT and AC-3' boundaries, but they have divergent 5'
      splice site and presumptive branch site sequences. Here, we report the accurate
      in vitro processing of these two divergent AT-AC introns and show that they
      belong to a functionally distinct subclass of AT-AC introns. Splicing of these
      introns does not require U12, U4atac, and U6atac snRNAs, but instead requires the
      major spliceosomal snRNAs U1, U2, U4, U5, and U6. Previous studies showed that G 
      -> A mutation at the first position and G --> C mutation at the last position of
      a conventional yeast or mammalian GT-AG intron suppress each other in vivo,
      suggesting that the first and last bases participate in an essential non-Watson
      Crick interaction. Our results show that such introns, hereafter termed AT-AC II
      introns, occur naturally and are spliced by a mechanism distinct from that
      responsible for processing of the apparently more common AT-AC I introns.

PMID- 9174095
TI  - Exact determination of UV-induced crosslinks in 16S ribosomal RNA in 30S
      ribosomal subunits.
AB  - Escherichia coli 30S ribosomal subunits were UV-irradiated to induce
      intramolecular crosslinks in the 16S rRNA. Intact 16S rRNA was purified and
      subjected to gel electrophoresis, under denaturing conditions, to separate
      molecules on the basis of the crosslinked loop size. Molecules separated this way
      were enriched for specific crosslinks and could be analyzed by the reverse
      transcription arrest assay to determine exact crosslinking sites. Thirteen
      crosslinking sites have been identified at single nucleotide resolution. Of
      these, eight are within or adjacent to secondary structure elements: one of these
      (C582 x G760) involves an interaction between nucleotides within an interior
      loop, one (C1402 x X1501) involves an interaction between nucleosides in adjacent
      base pairs, and the others involve interactions between nucleotides that are
      within junction regions (A441 x G494, U562 x U884, C934 x U1345, and U991 x
      U1212) or are interactions between nucleotides (C54 x A353 and U1052 x C1200)
      that somehow cross known base pairs. Five other crosslinks connect sites distant
      in the secondary structure and provide global constraints for the arrangement of
      RNA regions within RNA domains I and II (U244 x G894, G894 x A1468, C967 x C1400)
      and within domain III (U1126 x C1281 and A1093 x G1182). These crosslinks, known
      at single-nucleotide resolution, are useful in the prediction of local RNA
      regions, as well as the global structure.

PMID- 9174096
TI  - The protein cofactor allows the sequence of an RNase P ribozyme to diversify by
      maintaining the catalytically active structure of the enzyme.
AB  - To study the effect proteins have on the catalysis and evolution of RNA enzymes,
      we simulated evolution of RNase P catalytic M1 RNA in vitro, in the presence and
      absence of its C5 protein cofactor. In the presence of C5, functional M1 sequence
      variants (not catalytically active in the absence of C5) were selected in
      addition to those identical to M1. C5 maintains the catalytically active
      structure of the variants and allows for an enhanced spectrum of M1 molecules to
      function in the context of a ribonucleoprotein (RNP) complex. The generation of
      an RNP enzyme, requiring both RNA and protein components, from a catalytically
      active RNA molecule has implications for how modern RNP complexes evolved from
      ancestral RNAs.

PMID- 9174097
TI  - Poliovirus RNA recombination in cell-free extracts.
AB  - Poliovirus RNA has been shown to undergo homologous genetic recombination at a
      high frequency in infected human cells. Recently it has become possible to mimic
      the entire intracellular replicative cycle of poliovirus replication in
      cytoplasmic extracts prepared from HeLa cells, resulting in the generation of
      infectious poliovirions. The mechanism of poliovirus RNA recombination has been
      shown previously to be coupled to RNA replication, presumably by template
      switching during the replication of parental RNAs. Experiments were designed to
      test whether recombinant poliovirus RNA molecules are produced in a cell-free
      environment. Recombinant molecules generated bear marker sequences that can be
      detected physically by reverse transcription and PCR. We report here successful
      detection of poliovirus RNA recombination in a cell-free replication system. The
      frequency measured for cell-free RNA recombination between two polymorphic marker
      loci 656 nt apart was between 10(-2) and 10(-3) recombinants/genome, a frequency
      comparable to or slightly higher than that measured for RNA recombination in
      infected cells.

PMID- 9174098
TI  - Minimal templates directing accurate initiation of subgenomic RNA synthesis in
      vitro by the brome mosaic virus RNA-dependent RNA polymerase.
AB  - Short regions of (-)-strand brome mosaic virus (BMV) RNA3, proscripts, were shown
      to direct accurate in vitro synthesis of (+)-strand subgenomic RNA by the BMV RNA
      dependent RNA polymerase (RdRp), facilitating characterization of the sequences
      and/or structures directing subgenomic RNA synthesis. Proscripts retaining fewer
      than 8-nt of an 18-nt polyuridylate tract located just upstream of the core
      promoter sequence (French R, Ahlquist P, 1988, J Virol 62:2411-2420; Marsh LE,
      Dreher TW, Hall TC, 1988, Nucleic Acids Res 16:981-995) directed dramatically
      less synthesis of 26-nt or longer products. Original levels of RNA synthesis were
      not restored by replacement of the 3' polyuridylate tract with polyadenylate,
      polycytidylate, or polyguanylate tracts, or by movement of the polyuridylate
      tract to the 5' end of the proscript. The polyuridylate tract presumably binds
      some component(s) required for RdRp activity because the addition of poly(U) [but
      not poly(C)] RNA to RdRp reactions decreased RNA synthesis significantly. Quite
      surprisingly, deletions of the polyuridylate tract in proscripts directing
      synthesis of 24-nt or shorter products had little or no detrimental effect on
      subgenomic RNA synthesis, correlated with their inability to form a computer
      predicted stem-loop present in longer proscripts requiring the polyuridylate
      tract. Successive 3' and 5' deletions demonstrated that the minimal elements
      required for accurate initiation of subgenomic RNA synthesis are within a
      proscript of 22-nt.

PMID- 9174099
TI  - Regulation of tRNA suppressor activity by an intron-encoded polyadenylation
      signal.
AB  - A 26-nt sequence from the 3' UTR of the yeast GAL7 mRNA directs accurate and
      efficient cleavage and polyadenylation to form the 3' end of the GAL7 mRNA in
      vivo and in vitro. Here we asked whether this polyadenylation signal can function
      within the context of a tRNA. Insertion of the GAL7 signal into the intron of the
      dominant SUP4 nonsense suppressor allowed us to judge the effect of the insert on
      SUP4 function by observation of nonsense suppression efficiency in vivo. The GAL7
      signal impairs the function of SUP4 in an orientation-dependent manner in vivo,
      consistent with its ability to specify cleavage and polyadenylation in this
      context in vitro. Mutation of a UA repeat within the GAL7 signal restores SUP4
      function partially, consistent with the role of this repeat as an efficiency
      element in polyadenylation. Mutations that impair the mRNA 3' end-processing
      factors Rna14p and Rna15p restore suppressor function partially. Northern blot
      analysis, PCR amplification, and DNA sequence analysis show that the GAL7 signal
      directs polyadenylation within the body of pre-SUP4 and within the terminator,
      suggesting that polyadenylation inhibits 5' and 3' end processing, as well as
      removal of the pre-tRNA intron. These findings indicate that the GAL7
      polyadenylation signal is capable of targeting a pre-tRNA to the mRNA processing
      pathway.

PMID- 9174100
TI  - The association of nonsense mutation with exon-skipping in hprt mRNA of Chinese
      hamster ovary cells results from an artifact of RT-PCR.
AB  - RT-PCR of RNA from CHO cells with nonsense mutations in the hprt gene frequently
      detects minor hprt mRNA species lacking one or more exons. Many nonsense mutants
      also contain greatly reduced concentrations of the major, normally spliced hprt
      mRNA. In this study, we examined the hypothesis that exon-deleted mRNAs are
      normal constituents of CHO cells, but are not detected in wild-type parental
      cells and most missense mutants because their amplification is suppressed by
      relatively high concentrations of normally spliced hprt mRNA. A protocol designed
      to specifically detect exon-deleted mRNAs was conducted using RNA from parental
      cells and identified all the exon-deleted species typical of nonsense mutants.
      Quantitative analysis of parental cell RNA measured these exon-deleted mRNAs at <
      or = 0.7% of the abundance of the full-sized species. Nonsense and missense
      mutants had comparable amounts of exon-deleted mRNAs, which varied both above and
      below parental concentrations. The relative concentrations of particular exon
      deleted species could be explained by the location of nonsense mutations
      remaining in the mRNA or by structural effects of mutations on splicing. Exon
      deleted mRNAs were detected by RT-PCR when the concentration of the most abundant
      exon-deleted species was > or = 2% of the full-length mRNA. This occurred for
      mutants with nonsense mutations in internal exons. RT-PCR conditions were shown
      to suppress the amplification of exon-deleted species 40-fold when full-length
      mRNA was abundant, which occurred for parental lines and missense mutants. Our
      results verify that RT-PCR conditions can produce an artifactual association
      between nonsense mutation and exon-skipping when minor, exon-deleted mRNA is
      relatively enriched.

PMID- 9174101
TI  - Use of adenoviral VAI small RNA as a carrier for cytoplasmic delivery of
      ribozymes.
AB  - The in vivo effectiveness of therapeutic RNAs, like antisense molecules and
      ribozymes, relies on several features: RNA molecules need to be expressed at high
      levels in the correct cellular compartment as stable and active molecules. The
      exploitation of "natural" small RNA coding genes as expressing cassettes gives
      high chances to fulfill these requirements. We have investigated the utilization
      of the adenoviral VAI RNA as a cytoplasmatic carrier for expressing ribozymes
      against HIV-1. The conserved 5' leader sequence of HIV was chosen as a target,
      because it is present in all the viral transcripts and is highly conserved.
      Hammerhead ribozymes were substituted to different portions of the VAI RNA and
      the resulting chimera were tested in the in vivo system of Xenopus laevis oocytes
      for their level of accumulation, cellular compartmentalization, and assembly in
      specific ribonucleoparticles containing the La antigen. Interesting differences
      in the activity of the different chimera were found in both in vitro cleavage
      assays and S100 extracts of injected oocytes where the catalytic activity of the
      ribozymes in the RNP context can be analyzed.

PMID- 9174102
TI  - Conformation state of the ryanodine receptor and functional effects of ryanodine
      on skeletal muscle.
AB  - The ryanodine receptor (RyR) and the dihydropyridine (DHP) receptor (L-channels)
      comprise the main elements of the functional feet of the triadic element in
      skeletal muscle. These two main elements have conformational states that are
      regulated by the membrane potential and the consequent electrical field. The
      pharmacological action of ryanodine on skeletal muscle depends upon the
      physiological functional state of the RyR. At a resting potential of -90 m V,
      ryanodine at very low concentrations, 10(-11) M, causes the RyR to have a low
      conductance state which allows calcium to leak from the terminal cisternae of the
      sarcoplasmic reticulum and to be recycled with ATP utilization, leading to a
      marked increase in oxygen consumption and aerobic metabolism. At concentrations
      greater than 10(-6) M, ryanodine can cause a slowly developing contracture of
      resting muscle, inhibit the muscle twitch when the RyR complex is formed during
      stimulation, and, if formed before stimulation, accelerate the development of
      contracture. Biochemical studies have revealed that the RyR has four binding
      sites in which the conductance state depends upon the number of sites occupied by
      ryanodine. Our present understanding of the RyR-operated calcium channel is the
      result of an interdisciplinary approach in which each discipline (anatomy,
      physiology, biophysics, and biochemistry) contributes to our knowledge of the
      pharmacological action of ryanodine.

PMID- 9174103
TI  - 3'-Azido-3'-deoxythmidine uptake into isolated rat liver mitochondria and
      impairment of ADP/ATP translocator.
AB  - To gain some insight into the mechanism by which 3'-azido-3'-deoxythymidine (AZT)
      impairs mitochondrial metabolism, [14C]AZT uptake by rat liver mitochondria (RLM)
      in vitro was investigated. AZT accumulated in mitochondria in a time-dependent
      manner and entered the mitochondrial matrix. The rate of AZT uptake into
      mitochondria showed a hyperbolic dependence on the drug concentration and was
      inhibited by mersalyl, a thiol reagent that cannot enter mitochondria, thus
      showing that a membrane protein is involved in AZT transport. Investigation into
      the capability of AZT to affect certain mitochondrial carriers demonstrated that
      AZT was able to impair the ADP/ATP translocator, but had no effect on Pi,
      dicarboxylate, tricarboxylate, or oxodicarboxylate carriers. AZT inhibited
      ADP/ATP antiport in either mitochondria or mitoplasts in a competitive manner
      with different sensitivity (Ki values were 18.3 +/- 2.9 and 70.2 +/- 5.8 microM,
      respectively). Consistent with this were isotopic measurements showing that AZT
      accumulates in the intermembrane space. AZT does not use ADP/ATP carrier to enter
      mitochondria, as shown by the failure of both carboxyatractyloside (CAT) to
      inhibit AZT transport into mitochondria and AZT to induce ATP efflux from ATP
      loaded mitochondria. ADP/ATP translocator impairment by AZT as one of the
      biochemical processes responsible for the ATP deficiency syndrome is discussed.

PMID- 9174104
TI  - Differential induction of growth arrest inducible genes by selenium compounds.
AB  - The effects of two types of selenium compounds on the expression levels of growth
      arrest and DNA damage-inducible (gadd) genes and on selected cell death genes
      were examined in mouse mammary MOD cells to test the hypothesis that the
      diversity of selenium-induced cellular responses to these compounds could be
      distinguished by unique gene expression patterns. Whereas the expression patterns
      of known cell death-related genes (bcl-2 and bax) were not informative with
      respect to the cellular response patterns upon exposure to selenium compounds,
      time-dependent and selenium species-specific induction patterns were observed for
      gadd34, gadd45 and gadd153 genes. It was also observed that the MOD cells
      expressed a truncated p53 transcript but no detectable immunoreactive P53
      protein, indicating a null p53 phenotype. The fact that selenium compounds
      induced growth arrest and death of these cells and that these compounds induced
      specific patterns of expression of gadd genes indicates that these genes may
      mediate some selenium-induced cellular responses. The findings further imply that
      selenium compounds may be effective chemopreventive agents for human breast
      carcinogenesis, in which p53 mutations are frequent.

PMID- 9174105
TI  - Correlation between arachidonic acid oxygenation and luminol-induced
      chemiluminescence in neutrophils: inhibition by diethyldithiocarbamate.
AB  - Neutrophils from allergic subjects were hypersensitive to stimulation by low
      calcium ionophore concentration (0.15 microM), resulting in an increased
      formation of leukotriene B4 (LTB4), 5S-hydroxy-6,8,11,14-(E,Z,Z,Z)
      eicosatetraenoic acid (5-HETE), and other arachidonic acid metabolites through
      the 5-lipoxygenase pathway. In parallel, luminol-dependent chemiluminescence was
      also higher in neutrophils from allergic patients at the basal state and after
      stimulation by calcium ionophore, revealing an enhancement of radical oxygen
      species and peroxide production. The activity of glutathione peroxidase, the main
      enzyme responsible for hydroperoxide reduction, was lowered in these cells.
      Diethyl-dithiocarbamate (DTC) induced a concentration-dependent decrease in
      chemiluminescence and arachidonic acid metabolism after neutrophil stimulation.
      These data show that the elevation of arachidonic acid metabolism in neutrophils
      from allergic patients is strongly correlated with oxidative status. This
      elevation may be the consequence of an increased cellular hydroperoxide known to
      activate 5-lipoxygenase (5-LOX) activity and/or an increased arachidonic acid
      availability, due either to phospholipase A2 (PLA2) activation or inhibition of
      arachidonate reesterification into phospholipids. Lowering this oxidative status
      was associated with a concomitant decrease of this metabolism. Our results
      suggest that the effect of DTC may be the consequence of an inhibition of peroxyl
      radical and cellular lipid hydroperoxide production. Thus, DTC may modulate
      arachidonic acid metabolism in neutrophils by modulating the cellular
      hydroperoxide level.

PMID- 9174106
TI  - Requirement for epidermal growth factor receptor tyrosine kinase and for 12
      lipoxygenase activity in the expression of 12-lipoxygenase in human epidermoid
      carcinoma cells.
AB  - We studied the dependency of basal 12-lipoxygenase (12-LOX; arachidonate:oxygen
      12-oxidoreductase, EC 1.13.11.31) expression and activity on functional protein
      tyrosine kinase of the epidermal growth factor receptor (EGF-R) and on 12-LOX
      activity in human A431 epidermoid carcinoma cells. Treatment of cells with
      inhibitors of high specificity for EGF-R tyrosine kinase, namely PD 153035 and
      4,5-dianilinophthalimide (DAPH1), decreased cellular 12-LOX at mRNA, protein, and
      activity levels in a time- and dose-dependent manner, with PD 153035 being
      effective at concentrations below 1 microM. After 24-hr incubation with 10 microM
      PD 153035 or DAPH1, 12-LOX activity dropped to 14% (39%), and 12-LOX protein to
      25% (24%) of control level. Inhibition of 12-LOX activity by the compound N
      benzyl-N-hydroxy-5-phenylpentanamide (BHPP) also resulted in a substantial
      decrease in 12-LOX protein expression. 12-LOX mRNA levels were diminished or
      undetectable by reverse transcription-polymerase chain reaction after cell
      treatment with these inhibitors. Our results suggest that basal 12-LOX expression
      in A431 tumor cells largely depends on functional EGF-R tyrosine kinase, and that
      12-LOX activity is required in the EGF-elicited intracellular signaling
      maintaining the expression of 12-LOX.

PMID- 9174107
TI  - Effects of dual combinations of antifolates with atovaquone or dapsone on
      nucleotide levels in Plasmodium falciparum.
AB  - The triazine antifolates, cycloguanil and 4,6-diamino-1,2-dihydro-2,2-dimethyl-1
      [(2,4,5-trichlorophenoxy)propy loxy]-1,3,5-triazine hydrobromide (WR99210), and
      their parent biguanide compounds, proguanil and N-[3-(2,4,5
      trichlorophenoxy)propyloxy]-n-(1-methylethyl)-imido dicarbonimidic-diamine
      hydrochloride (PS-15), were tested in combination with a series of antimalarial
      drugs for synergism against Plasmodium falciparum growing in erythrocytic
      culture. Four synergistic combinations were found: cycloguanil dapsone, WR99210
      dapsone, proguanil-atovaquone, and PS-15-atovaquone. Cycloguanil-dapsone or
      WR99210-dapsone had a profound suppressive effect on the concentration of dTTP in
      parasites while that of dATP increased. Depletion of dTTP is consistent with
      cycloguanil or WR99210 inhibiting dihydrofolate reductase and dapsone inhibiting
      dihydropteroate synthase. For the combinations proguanil-atovaquone and PS-15
      atovaquone, the levels of nucleoside triphosphates (NTPs) and dNTPs were
      generally suppressed, suggesting that inhibition is not through nucleotide
      pathways but probably through another metabolic mechanism(s). Combinations of two
      synergistic pairs of antimalarial drugs, (proguanil-atovaquone)-(cycloguanil
      dapsone) and (PS-15-atovaquone)-(WR99210-dapsone), were tested, and it was found
      that NTPs and dNTPs decreased much more than for a single synergistic
      combination. Dual synergistic combinations could play an important role in the
      therapy of multidrug-resistant malaria, just as combination chemotherapy is used
      to treat cancer.

PMID- 9174108
TI  - Effect of the histone deacetylase inhibitor trichostatin A on the responsiveness
      of rat hepatocytes to dioxin.
AB  - Since histone acetylation has been implicated in the facilitation of specific
      gene transcription, we investigated the effect of increasing histone acetylation
      through inhibition of histone deacetylase on 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) induction of P4501A activity in cultured rat hepatocytes. Inhibition of
      histone deacetylation was accomplished with addition of trichostatin A (TSA) to
      the incubation medium, and P4501A activity was measured spectrofluorometrically
      by determination of the rate of resorufin formation by ethoxyresorufin-O
      deethylase (EROD). While TSA alone (5-200 ng/mL) had no effect on EROD activity,
      TSA potentiated the effect of various concentrations (10(-12) to 10(-10) M) of
      TCDD. Addition of 200 ng TSA/mL with TCDD resulted in an increased EROD activity
      of approximately 200% compared with TCDD alone. When TSA was removed from the
      cells after various incubation times (2, 6, 24 hr) by successive washings with
      TSA-free medium, it was determined that TSA was required for 24 hr in order to
      potentiate the effects of a 48-hr incubation with TCDD. In addition to
      measurement of EROD activity, P4501A1 and 1A2 microsomal protein were determined
      by western immunoblotting analysis. While neither P4501A1 nor 1A2 was detectable
      in the presence of TSA alone, P4501A1 was present after incubation of cells with
      TCDD in the presence or absence of TSA. TCDD plus TSA also resulted in the
      formation of P4501A2. The results of this study suggest an important role for
      histone acetylation in the action of TCDD on induction of P4501A enzymes.

PMID- 9174109
TI  - Differential cholinoceptor subtype-dependent activation of signal transduction
      pathways in neonatal versus adult rat atria.
AB  - In this study, we investigated the expression and distribution of muscarinic
      cholinergic receptors (mAChRs) and the different signaling pathways associated
      with mAChR activation in atria isolated from adult and neonatal rats. Carbachol
      stimulation of mAChRs in both neonatal and adult rat atria led to a negative
      inotropic response with activation of phosphoinositide hydrolysis, an increase in
      cyclic GMP levels, and a decrease in cyclic AMP production. However, compared
      with adult atria, neonatal atria showed hypersensitivity in the contractile
      effect induced by carbachol. Pharmacological analysis with mAChR antagonists
      indicated that M1 and M2 mAChR subtypes are important mediators of the response
      to carbachol in neonatal atria. In contrast, in adult atria the effect of the
      agonist was coupled only to the M2 mAChR subtype. Moreover, an increased number
      of total mAChRs was labeled in neonatal atrial membranes compared with those of
      adults. Although a predominant M2 mAChR population is expressed in atria at both
      stages of development studied, competition binding parameters calculated for
      carbachol indicated the presence of high-affinity binding sites, with higher
      affinity in neonates than in adults. These results suggest that the differences
      observed between neonatal and adult atria in their response to a cholinergic
      agonist may be related to differential expression of mAChR subtypes and/or
      changes in functional coupling of mAChR subtypes during development.

PMID- 9174110
TI  - Effects of transcription and translation inhibitors on a human gastric carcinoma
      cell line. Potential role of Bcl-X(S) in apoptosis triggered by these inhibitors.
AB  - The effects of the macromolecular synthesis inhibitors 5,6-dichloro-1-beta-D
      ribofuranosyl benzimidazole (DRB), actinomycin D, and cycloheximide on the human
      gastric cancer TMK-1 cell line were studied. These agents inhibited DNA, RNA, or
      protein synthesis efficiently and induced cell death rapidly in a wide range of
      concentrations. After 8 hr of exposure to these agents, the cells exhibited
      morphological features of apoptosis, including cell shrinkage, nuclear
      condensation, DNA fragmentation, and formation of apoptotic bodies. Western blot
      analysis revealed that these inhibitors altered the protein levels of apoptosis
      related gene products such as c-Myc, Bcl-X(S), and the mutant p53 (mp53) in TMK-1
      cells markedly. The c-myc mRNA and protein levels were decreased initially and
      were then induced markedly to a new level after 4 hr of exposure to DRB, a RNA
      polymerase II inhibitor. The Bcl-X(S) levels were increased rapidly after
      treatment with all of these agents, whereas the levels of Bcl-X(L) and Bax
      remained largely unchanged. Northern blot analysis indicated that the c-myc
      overexpression is concomitant to DRB-induced DNA fragmentation and that the
      increased mp53 protein level was mainly a posttranscriptional event. Our
      observations suggest that the up-regulation of Bcl-X(S) may serve as an important
      mechanism for the apoptosis triggered by these inhibitors. This study also
      provides evidence for the notion that interference with the cellular survival
      pathway may lead to apoptosis.

PMID- 9174111
TI  - Effect of intrathecally administered local anesthetics on protein phosphorylation
      in the spinal cord.
AB  - To elucidate the biochemical mechanisms of spinal anesthesia, we studied the
      effects of procaine and tetracaine on protein phosphorylation in the mouse spinal
      cord. Mice were injected intrathecally with either procaine, tetracaine (67
      mM/approximately 2%, 10 microL, N = 5/drug), or saline (N = 4/group). Five
      minutes after injection, animals were killed with a guillotine, and the spinal
      cord was removed. The caudal 3-cm cord segment was homogenized and centrifuged,
      and an aliquot of the supernatant was used for phosphorylation assays. Calcium
      dependent phosphorylation was initiated by incubating the samples in buffer
      containing [gamma-32P]ATP at 37 degrees for 30 min. The proteins were
      electrophoresed using slab gel and two-dimensional electrophoresis, and
      phosphorylated proteins were visualized by autoradiography. The data demonstrated
      that spinal anesthesia changes the phosphorylation state of five endogenous
      substrate proteins with apparent molecular masses of 130 (protein-a), 105
      (protein-b), 55 (protein-c), 47 (protein-d), and 33 (protein-e) kDa. In two
      dimensional electrophoresis, protein-a resolved into two proteins (a1 and a2).
      Analysis of variance of the densitometric data suggested a significant effect for
      the treatment (F(2,16) 735, P < 0.00005). Post hoc comparisons with the saline
      treated controls, using the Newman-Keuls test, indicated that local anesthetics
      significantly affected phosphoproteins (P < 0.05) except for protein-al in the
      tetracaine-treated group. Further characterization of these phosphoproteins
      should aid in determining their role in the signal transduction cascade affected
      by spinal anesthesia.

PMID- 9174112
TI  - Adaptation to oxidative stress: quinone-mediated protection of signaling in rat
      lung epithelial L2 cells.
AB  - Cells can respond to a sublethal oxidative stress by up-regulating their
      intracellular glutathione (GSH) pool. Such increased GSH concentration is likely
      to be protective against further oxidative challenge, and, in fact, pre-exposure
      to low levels of oxidants confers increased cellular resistance to subsequent
      greater oxidative stress. Previously, we have shown that pretreatment of rat lung
      epithelial L2 cells with sublethal concentrations of tert-butylhydroquinone
      (TBHQ) increases intracellular GSH concentration in a concentration- and time
      dependent manner. This increase resulted from up-regulation of both gamma
      glutamyltranspeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS).
      Therefore, we investigated whether such increased GSH concentration protected
      these cells against a subtle loss in function caused by a subsequent challenge
      with sublethal concentrations of tert-butyl hydroperoxide (tBOOH) (< or = 200
      microM), mimicking a physiological oxidative stress. Activation of L2 cell
      purinoreceptors with 100 microM ADP caused an elevation of intracellular Ca2+.
      This response was suppressed by a brief pre-exposure to tBOOH. The inhibition,
      however, was alleviated dramatically by a 16-hr pretreatment with 50 microM TBHQ.
      The same TBHQ pretreatment also protected the cells from ATP-depletion induced by
      tBOOH. L-Buthionine S,R-sulfoximine (BSO), an irreversible inhibitor of GCS,
      prevented the increase in intracellular GSH and also completely removed the
      protection by TBHQ in maintaining the ATP level. Thus, pre-exposure to a
      sublethal level of TBHQ results in protection of cell functions from
      hydroperoxide toxicity. This protection appears to depend on alteration of the
      intracellular GSH pool, the modulation of which constitutes an adaptive response
      to oxidative stress.

PMID- 9174113
TI  - Inhibition of influenza virus fusion by polyanionic proteins.
AB  - Anionic charge-modified human serum albumin (HSA) has previously been shown to
      exert potent in vitro activity against human immunodeficiency virus type 1 (HIV
      1). In these studies, introduction of the additional negative charges was
      performed by derivatizing the epsilon-amino groups of lysine residues with
      succinic (Suc-HSA) or cis-aconitic anhydride (Aco-HSA), by which primary amino
      groups are replaced with carboxylic acids. The anti-HIV-1 activity was related to
      inhibition of gp41-mediated membrane fusion. Here, we investigated the activity
      of aconitylated and succinylated proteins on influenza virus membrane fusion,
      which is mediated by the viral membrane glycoprotein hemagglutinin (HA). Aco-HSA
      and Suc-HSA markedly inhibited the rates and extents of fusion of fluorescently
      labeled virosomes bearing influenza HA, with target membranes derived from
      erythrocytes. The inhibitory activity was dependent on the overall negative
      charge density; HSA modified with 36 or less extra negative charges failed to
      inhibit fusion. The inhibition of fusion showed a certain degree of specificity
      for the protein carrying the negative charges: polyanionic HSA and beta
      lactoglobulin A derivatives had fusion-inhibitory activity, whereas succinylated
      BSA, lactalbumin, lactoferrin, lysozyme, and transferrin were inactive. Aco60-HSA
      and Aco-beta-lactoglobulin A inhibited influenza virus membrane fusion in a
      concentration-dependent manner, IC50 values being about 4 and 10 microg/mL,
      respectively. HA-mediated membrane fusion is pH dependent. Aco60-HSA did not
      induce a shift in the pH threshold or in the pH optimum. Fusion with liposomes of
      another low pH-dependent virus, Semliki Forest virus, was not specifically
      affected by any of the compounds reported here. In view of some structural and
      functional similarities between influenza HA and the HIV-1 gp120/gp41 complex, it
      is tempting to postulate that the current results might have some implications
      for the anti-HIV-1 mechanism of polyanionic proteins.

PMID- 9174114
TI  - The regulation of CD11b integrin levels on human blood leukocytes and leukotriene
      B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111).
AB  - CD11b is part of the beta2-integrin Mac-1 and plays an important role in
      neutrophil adhesion. Leukotriene B4 (LTB4) is an active upregulator of neutrophil
      CD11b-expression, acts as a potent chemoattractant to neutrophils and is also
      known to upmodulate epidermal proliferation. We performed a placebo-controlled
      study on LY293111, an oral LTB4 receptor antagonist. Twenty healthy male
      volunteers were randomised over three treatment groups that received placebo, 48
      mg, or 200 mg drug twice daily for 10 days. Before and after treatment, flow
      cytometrical CD11b assessment was performed on in vitro LTB4-stimulated
      peripheral blood neutrophils. Additionally, skin biopsies were taken at 24 and 72
      h after epicutaneous LTB4 application, before and after treatment. The effects on
      skin were assessed immunohistochemically using various markers. All observed
      effects were dose related. CD11b upregulation on blood neutrophils was
      significantly suppressed in both treatment groups compared to placebo. In skin, a
      significant suppression of inflammation and hyperproliferation occurred.
      Pronounced inhibition was observed on neutrophil migration into the epidermis and
      the inflammatory infiltrate was decreased. A similar but weaker response was seen
      in the dermis. The number of cycling cells as well as suprabasal keratin-16
      expression were decreased in both treatment groups. LY293111 proved to be a
      potent inhibitor of LTB4-induced cutaneous inflammation and hyperproliferation.
      The potent antiinflammatory effect in vivo and the fact that in the present study
      the compound showed no clinically significant side effects make it an interesting
      drug in the future treatment of inflammatory conditions predominated by
      neutrophils.

PMID- 9174115
TI  - Comparative quantification of two hepatic UDP-glucuronosyltransferase bilirubin
      isoforms mRNAs in various thyroid states in rat.
AB  - The study was designed to compare the effects of 3,5,3' triiodo-L-thyronine (L
      T3) on the levels of hepatic mRNAs encoding two UDP-glucuronosyltransferase
      bilirubin isoforms (UGT1*1 and UGT1*0) in rats, by reverse transcription and
      quantitative polymerase chain reaction (RT-PCR). The administration of L-T3
      decreased the UGT1*O mRNA by 2.2-fold and that of UGT1*1 by only 1.4-fold. In
      contrast, thyroidectomy increased the UGT1*O mRNA level by twofold but did not
      change that of the UGT1*1 isoform significantly. Interestingly, treatment with a
      known inducer of UGT bilirubin, ciprofibrate, induced the hepatic mRNA levels
      encoding for the UGT1*0 isoform by 3.5-fold and for the UGT1*1 isoform by only
      twofold. The results indicate for the first time that, although UGT1*1 mRNA is
      indeed a major transcript, its level is weakly affected by these compounds. In
      contrast, the minor UGT1*0 form is much more sensitive both to the action of this
      drug and to changes in thyroid status. The data support the notion that the
      various members of exon1 of the UGT1 locus have their own individual regulatory
      region.

PMID- 9174116
TI  - Involvement of amino acids 361 to 364 of human topoisomerase I in camptothecin
      resistance and enzyme catalysis.
AB  - Camptothecins are antineoplastic drugs that specifically target the enzyme DNA
      topoisomerase I. Prior work has identified a human topoisomerase I mutation,
      F361S, that confers resistance to camptothecin. We now demonstrate that
      substitutions in the 361-364 region can alter DNA cleavage/ligation by the
      enzyme. The defective catalysis exhibited by certain mutants likely relates to an
      impaired interaction with DNA, since these enzymes are more sensitive to the
      inhibitory effects of DNA binding ligands. Moreover, studies with peptides and
      fusion proteins suggest that the 361-364 region may bind DNA directly. The
      finding that the 361-364 region is involved in both enzyme catalysis and
      camptothecin resistance suggests that this region is part of the active site of
      human topoisomerase I and that camptothecin may interact with the enzyme at this
      site.

PMID- 9174117
TI  - Induction and post-transcriptional suppression of hepatic cytochrome P450 1A1 by
      3,3',4,4'-tetrachlorobiphenyl.
AB  - 3,3',4,4'-Tetrachlorobiphenyl (TCB) can induce and inhibit cytochrome P450 1A1
      (CYP1A1) in vertebrates. TCB may also suppress CYP1A1 protein levels, but the
      mechanism is unknown. This study examined transcriptional and translational
      aspects of hepatic CYP1A1 regulation in the fish scup (Stenotomus chrysops) given
      single intraperitoneal injections of low (0.1 mg/kg) or high (5 mg/kg) doses of
      TCB, and sampled over 16 days. The low dose strongly induced hepatic CYP1A1 mRNA
      (25-fold), protein (12-fold), and activity [ethoxyresorufin O-deethylase (EROD)]
      (15-fold). The high dose also strongly induced CYP1A1 mRNA (29-fold), in a
      pattern like that at the low dose, but microsomal CYP1A1 protein content was
      induced only 4-fold and EROD rates were near control levels. Both TCB doses
      caused similar increases in microsomal cytochrome b5 content, and in rates of
      NADPH-cytochrome c (P450) reductase and UDP-glucuronosyltransferase (with p
      nitrophenol). The contents of CYP forms other than CYP1A1 (putative CYP2B or
      CYP3A) were only weakly affected by TCB at either dose. The strong and largely
      specific post-transcriptional suppression of CYP1A1 content was associated with
      high concentrations of TCB measured in the liver. Incubation of scup hepatic
      microsomes with TCB plus NADPH led to a time-dependent inactivation of CYP1A1
      that was distinct from catalytic inhibition, and appeared not to involve reactive
      metabolites of TCB. This in vitro result suggests that TCB may inactivate CYP1A1
      in vivo, which could account for the apparent antagonistic effect of TCB on
      CYP1A1 induction.

PMID- 9174118
TI  - Molecular basis for deficient acetaminophen glucuronidation in cats. An
      interspecies comparison of enzyme kinetics in liver microsomes.
AB  - Cats are highly susceptible to acetaminophen toxicity because of deficient
      glucuronidation of this drug in vivo. The enzyme kinetic basis for this defect is
      unknown. Therefore, the kinetic properties of acetaminophen UDP
      glucuronosyltransferase (acetaminophen-UGT) were investigated, using hepatic
      microsomes from cats (N = 4) compared with those of species that are less
      sensitive to acetaminophen intoxication including dogs (N = 4), humans (N = 4),
      and six other mammalian species (one liver from each). Gunn rats were also
      studied, since they express defective UGT family 1 isoenzymes and are also prone
      to acetaminophen toxicity. Acetaminophen kinetics were biphasic in all instances
      with distinct high and low affinity components. Km values for the high affinity
      activity in cat microsomes (0.31 +/- 0.1 mM; mean +/- SEM) were intermediate
      between those of dogs (0.11 +/- 0.02 mM) and humans (0.60 +/- 0.06 mM) and other
      species (0.22 to 6.7 mM; range). On the other hand, high affinity Vmax values
      were over 10-fold less in cat microsomes (0.025 +/- 0.006 nmol/min/mg) than in
      dogs (0.92 +/- 0.09 nmol/min/mg) and humans (0.27 +/- 0.09 nmol/min/mg); and over
      5-fold less compared with microsomes from other species (range 0.13 to 7.63
      nmol/min/mg). Gunn rat microsomes showed a similar 10-fold difference in high
      affinity Vmax values between the homozygous mutant (0.67 nmol/min/mg) and
      homozygous normal (6.75 nmol/min/mg) animals. These results demonstrate that,
      relative to a number of other species, cats have remarkably low hepatic levels of
      a high affinity acetaminophen-UGT. This difference is sufficient enough to
      explain poor glucuronidation of acetaminophen in vivo and susceptibility to
      acetaminophen intoxication.

PMID- 9174119
TI  - Didehydroretinoic acid: retinoid receptor-mediated transcriptional activation and
      binding properties.
AB  - All-trans-3,4-Didehydroretinoic acid (vitamin A2 acid; DDRA) is one of the
      retinoids present in human skin, the most responsive tissue to retinoid
      treatment. To understand the mechanism of action of DDRA in the control of
      differentiation and tumorigenesis, we studied its interaction with cellular
      retinoic acid-binding proteins (CRABPs) and nuclear all-trans-retinoic acid (RA)
      receptors (RARs), and 9-cis-retinoic acid receptors (RXRs). The IC50 plots of
      DDRA for inhibition of [3H]RA binding to CRABP I and II and to RAR alpha, beta
      and gamma illustrate that this retinoid binds with the same affinity as RA to
      these proteins. DDRA, however, showed higher affinity than RA for RXR alpha.
      Evaluation of the transcriptional activation potential of DDRA in CV-1 cells
      showed that this retinoid induced RAR alpha-mediated transcription to the same
      magnitude as RA in the 10(-9) to 10(-6) M concentration range. However, in
      comparison to RA, DDRA produced a 2- to 3-fold higher activation of the
      transcription mediated by RXR alpha homodimers, as well as RAR beta-RXR alpha
      heterodimers. These results suggest that the biological activity of retinoids in
      the skin may be attained through the joint potential of both RA and DDRA.

PMID- 9174120
TI  - Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE)
      inhibitors in allergen-specific human T lymphocyte clones.
AB  - Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural
      and functional studies suggest a key role for IL-13 in the genesis of chronic
      allergic inflammation; as such, its pharmacologic inhibition is of potential
      clinical utility. We studied the pharmacologic regulation of IL-13 expression by
      cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a
      major allergen of short ragweed, Ambrosia artemisiifolia)-specific T cell clones
      derived from a ragweed allergic, asthmatic subject. Proliferative responses of
      these cells were down-regulated by rolipram, a PDE4 inhibitor (% inhibitionMAX =
      67%; IC50 = 20 microM). While the PDE3 inhibitor siguazodan provided no
      independent efficacy (IC50 > 10(-4) M), an increased efficacy of rolipram in the
      presence of 10(-5) M siguazodan was noted at 10(-6), 10(-5), and 10(-4) M
      rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC50 values remained
      unchanged between assays using the PDE4 inhibitor with or without the PDE3
      inhibitor. Both IL-13 gene expression and protein secretion into culture
      supernatants were down-regulated by the PDE4 inhibitor (P < or = 0.005). Once
      again, the use of a PDE3 inhibitor provided no independent efficacy (P > or =
      0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the
      PDE3 inhibitor was not apparent (P > or = 0.3). IL-13 production from clones with
      Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the
      PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors
      may be mediated, in part, by down-regulation of IL-13.

PMID- 9174121
TI  - Increases in the mRNA levels of gamma-glutamyltransferase and heme oxygenase-1 in
      the rat lung after ozone exposure.
AB  - gamma-Glutamyltransferase (GGT) and heme oxygenase-1 (HO-1) are induced by
      chemical and physical stresses producing an oxidative burden on tissues and
      cells. Both enzymes are proposed to have an antioxidant role in protecting cells
      and tissues from oxidative burden. To explore the effects of ozone (O3), the
      major oxidant in photochemical smog, on the expression of GGT and HO-1 genes in
      the lung, we exposed rats to 0.4 ppm O3 for up to 7 days. After exposures, mRNA
      levels of GGT and HO-1 in the lung were measured by RNA blot analysis. Although a
      1-day exposure did not change either GGT or HO-1 mRNA levels in the lung, both
      genes responded to prolonged exposure to O3. GGT mRNA was increased to 149% (P <
      0.01) and 158% (P < 0.01) of the control by 3- and 7-day exposures, respectively.
      HO-1 mRNA was also elevated to 174% (P < 0.01) and 184% (P < 0.001) of the
      control after 3- and 7-day exposures, respectively. The elevation of GGT and HO-1
      mRNA after prolonged exposure to O3 suggests that expression of these genes is
      not involved in the acute respiratory response, but in the recovery process from
      lung damage induced by O3.

PMID- 9174122
TI  - Glucocorticoid receptor function possibly modulates cell-cell interactions in
      osteoblastic metastases on rat skeleton.
AB  - We analysed the glucocorticoid receptor (GR) function and its ability to modulate
      cell-cell interactions between the PA-III rat prostate cancer and UMR 106
      osteoblast-like rat osteosarcoma cells as an in vitro model for studying GR
      function in PA-III cell-induced tumor and blastic reaction in rat bone. Intact GR
      was detected by ligand binding assays, DNA band-shift, and GR trans-activation
      analysis of PA-III and UMR 106 cells transiently transfected with the mouse
      mammary tumor virus thymidine kinase-chloramphenicol acetyltransferase reporter
      gene. Dexamethasone and transforming growth factor beta 1 (TGFbeta1) inhibited
      the growth of PA-III and UMR 106 cells. Dexamethasone's inhibition of PA-III and
      UMR 106 cells was reversed by anti-TGFbeta1 antibody and exogenous insulin-like
      growth factor I (IGF-I). Exogenous IGF-I, urokinase-type plasminogen activator
      (uPA), UMR 106 conditioned media (CM) and PA-III CM stimulated the proliferation
      of PA-III and UMR 106 cells. The mitogenic activity exerted by uPA and PA-III CM
      in UMR 106 cells was completely neutralized by anti-IGF-I specific antibody. In
      addition, dexamethasone up-regulated TGFbeta1 mRNA and down-regulated uPA mRNA
      expression in PA-III cells without affecting TGFbeta1 and uPA mRNA expression in
      UMR 106 cells. These data suggested that TGFbeta1, uPA, and IGF-I mediate at
      least in part cell-cell interactions and GR function in PA-III prostate cancer
      and UMR 106 osteosarcoma cells.

PMID- 9174123
TI  - Primary prostatic epithelial cell binding to human bone marrow stroma and the
      role of alpha2beta1 integrin.
AB  - Prostate cancer selectively metastasises to the bone. To investigate the
      importance of prostate epithelial cell adhesion to bone marrow cells in this
      process we examined the binding of human primary prostatic epithelial cells (PEC)
      to human bone marrow stromal cultures (BMS). We found that PEC derived from both
      malignant and benign tissue showed greater adhesion to BMS than to benign
      prostatic fibroblasts (median difference was 340% and 200% respectively), skin
      fibroblasts or plastic tissue culture plates. Adhesion to BMS grown from the bone
      marrow of patients with prostatic skeletal metastases was no different from those
      grown from normal bone marrow. The role of integrin molecules in these cell
      interactions was determined. Collagen type I and fibronectin were found to
      increase PEC adhesion whereas vitronectin and laminin did not. Inhibition studies
      demonstrated that although there was heterogeneity between samples, antibodies
      against the integrins alpha2 and beta1 consistently inhibited PEC binding to BMS.
      This result was more marked for PEC derived from malignant tissue. However
      studies investigating the effects of disintegrins and anti-alpha3 and anti-alpha5
      integrins indicated that for a percentage of patients these integrins and RGD
      (arginine, glycine, aspartamine)-dependent binding pathways were also involved.
      In summary, the results indicate that BMS are adherent to primary PEC derived
      from both malignant and benign tissue. The integrin alpha2beta1 is a major
      contributor to this interaction.

PMID- 9174124
TI  - N-myc over-expression downregulates alpha3beta1 integrin expression in human Saos
      2 osteosarcoma cells.
AB  - Alterations in adhesion to the extracellular matrix mediated by integrin
      receptors are commonly observed in a wide variety of transformed/tumor classes.
      Reductions in the expression of several integrin subunits have been documented in
      human neuroblastoma cell lines that over-express the neuroblastoma-associated
      oncogene N-myc. Neuroblastoma cells transfected with a cDNA encoding N-myc on a
      high-expression plasmid exhibit greatly reduced levels of alpha2, alpha3 and
      beta1 integrin subunits with concomitant rounding of cells on substrata. In the
      current studies, we examined whether integrin downregulation by N-myc is cell
      type specific by transfecting a human N-myc cDNA into Saos-2 human osteosarcoma
      cells and evaluating integrin expression. Several N-myc-expressing cell lines
      were isolated which exhibit reduced levels of beta1 integrin subunit protein and
      significant alteration in cell morphology - these cell lines resemble N-myc-over
      expressing neuroblastoma cells. In addition to reduced beta1 subunit levels, the
      osteosarcoma-derived N-myc transfectants exhibit little or no alpha3beta1
      integrin complexes, either intracellular or at the cell surface. Finally, reduced
      amounts of alpha3 integrin subunit in these cell lines occur at the level of
      alpha3 integrin mRNA, although post-transcriptional mechanisms may also be
      involved, particularly with inability of pre-beta1 protein to mature. These
      results confirm our previous studies demonstrating integrin downregulation by an
      N-myc-dependent process and, in addition, demonstrate lack of cell-type
      specificity in the action of N-myc on integrin extracellular matrix receptor
      expression when comparing neural precursor (neuroblastoma) cells with connective
      tissue (osteosarcoma) cells.

PMID- 9174125
TI  - The efficacy of doxorubicin microspheres for hepatic micrometastases in a rat
      tumour model.
AB  - The use of sustained-release microspheres is of potential benefit as an adjuvant
      treatment for patients with occult hepatic micrometastases. This study
      investigates the response of a model of implantable adenocarcinoma
      micrometastases in the livers of DA rats following the intraportal injection of
      doxorubicin-incorporated ion-exchange microspheres compared to free drug bolus
      administration. A point-counting technique was used to determine the percentage
      of liver consisting of tumour 13 days after treatment. This was used as an
      indicator of tumour response, as was the derived tumour mass. There was a
      significantly higher tumour response in animals treated with the microspheres
      compared to animals treated with free drug delivered at the same concentration.
      This effect, however, was shown to decrease with a delay in the time of
      treatment. The tumour response of the sustained-release microspheres was achieved
      in the absence of any detectable local or systemic toxicity. This study
      demonstrates the potential of sustained-release microspheres in the treatment of
      patients with hepatic micrometastases.

PMID- 9174126
TI  - In situ hybridization studies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2
      expression in human prostate cancer.
AB  - The expression of MMP-2, MMP-9, TIMP-1, TIMP-2, and the urokinase receptor were
      examined in fetal and normal prostate tissues, benign prostatic hyperplasia and
      prostate cancer (n = 117). In situ hybridization with digoxigenin-labeled
      oligonucleotide probes demonstrated that TIMP-1 and TIMP-2 were expressed at
      elevated levels in the stroma of Gleason sum 5 tissues, whereas MMP-2 and MMP-9
      were expressed at relatively low levels. In higher Gleason sum tissues (GS 8-10),
      TIMP-1 and TIMP-2 were not expressed, whereas MMP-2 and MMP-9 were intensely
      expressed. Furthermore, TIMP-1 and TIMP-2 expression was high in organ-confined
      specimens (OC, n = 43), somewhat lower in specimens with capsular penetration
      (CP, n = 29), and low or negative in samples with surgical margin/seminal vesicle
      (M/SV, n = 17) and lymph node (LN, n = 13) involvement. In contrast, MMP-2 and
      MMP-9 expression was low in the OC tissues; and noticeably higher in CP, M/SV,
      and LN specimens. Finally, correlation of TIMP and MMP expression with GS and
      pathological stage versus cure rate further revealed that a high percentage of
      organ-confined, GS 5 specimens expressing TIMP and little MMP were cured. In
      comparison, few of the GS 7-10 patients with capsular penetration and expressing
      MMP and little TIMP were cured. The data suggest that TIMP-1 (and TIMP-2) and MMP
      2 (and MMP-9) are independent predictors of outcome.

PMID- 9174127
TI  - Suppression of human melanoma metastasis following introduction of chromosome 6
      is independent of NME1 (Nm23).
AB  - Metastasis is suppressed more than 95% following microcell-mediated transfer of a
      single copy of neomycin-tagged human chromosome 6 (neo6) into the human melanoma
      cell lines C8161 and MelJuSo. Concomitant with metastasis suppression is
      upregulation of NME1 (Nm23-H1) mRNA and protein expression. The purposes of this
      study were to determine whether NME1 expression was responsible for metastasis
      suppression in neo6/melanoma hybrids, and whether genes on chromosome 6 regulate
      NME1. Using neo6/C8161 cells, transfection of CAT reporter constructs linked to
      the NME1 promoter failed to consistently induce CAT. Therefore, it does not
      appear that genes on chromosome 6 directly control transcription of NME1.
      Transfection and overexpression of NME1 in MelJuSo, under the control of the CMV
      promoter, resulted in 40-80% inhibition of lung metastasis following i.v.
      inoculation of 2 x 10(5) cells. Only one transfectant of C8161 subclone 9
      (C8161cl.9) cells was suppressed for metastasis. Control transfections with
      pCMVneo or pSV2neo did not suppress metastasis in either cell line. Taken
      together, these data suggest that NME1 can reduce metastatic potential of some
      human melanoma cells; but, this inhibitory activity appears to be independent of
      the metastasis suppression following introduction of chromosome 6 into C8161 and
      MelJuSo human melanoma cell lines.

PMID- 9174128
TI  - Inhibitory effects of fluorinated pyrimidines, 5'-DFUR, UFT and T-506, in a model
      of hepatic metastasis of mouse colon 26 adenocarcinoma-assessment of inhibitory
      activity and adverse reactions at the maximum tolerated dose.
AB  - The effects of fluorinated pyrimidines, 5'-DFUR, UFT and T-506, on a mouse model
      of hepatic metastasis were assessed in regard to inhibitory activity and adverse
      reactions at the maximum tolerated dose. The model was prepared by injecting the
      mouse colonic cancer cell line, colon 26, into the portal vein of CDF1 mice. At
      the treatment regimens employed for 5'-DFUR (1.0 mmol/kg/day, p.o., daily from
      days 1 to 7), UFT (0.1 mmol/kg/day, p.o., daily from days 1 to 7), and T-506
      (0.074 mmol/kg/day, i.v., days 1, 4, 7, and 10), complete inhibition of hepatic
      metastasis was obtained in six out of seven mice (85.7%) with 5'-DFUR, and in
      five out of six mice (83.3%) with T-506. Significant inhibition of hepatic
      metastasis was not achieved with UFT (3/7, 42.9%). 5'-DFUR and T-506 showed the
      highest rate of inhibition of hepatic metastasis, suggesting that these drugs
      would be effective for the prophylactic treatment of metastatic disease. 5'-DFUR
      and UFT exhibited mild adverse reactions such as loss of body weight.

PMID- 9174130
TI  - Identification and characterization of motility stimulating factor secreted from
      pancreatic cancer cells: role in tumor invasion and metastasis.
AB  - Cell motility is an important factor in the process of invasion and metastasis of
      tumor. In this study, the relationship between cell motility and experimental
      metastatic potential was examined using two human pancreatic cancer cell lines,
      SW1990 and PANC-1. Serum-free conditioned medium from the highly metastatic cell
      line SW1990 was found to contain a factor that stimulated the migration of and
      induced a fibroblast-like morphological change in the weakly metastatic cell line
      PANC-1. Preincubation of PANC-1 cells with SW1990 conditioned medium (SW-C.M.)
      induced liver metastasis following splenic injection of PANC-1 cells in nude
      mice, although no liver metastasis was observed without pretreatment of SW-C.M.
      This factor, temporarily termed PDMF (pancreatic cancer-derived motility factor)
      is a heparin non-binding protein having a molecular weight of 40 kDa calculated
      by gel-filtration HPLC which acts not only chemotactically but also
      chemokinetically, and also acts mainly in a paracrine fashion. However, this
      factor had no effect on the proliferation of PANC-1 cells; it therefore appears
      to be a so-called motility factor. Only TGF-beta1 and IL-6 were recognized in the
      SW-C.M. among cytokines thought to stimulate cell motility. These cytokines
      stimulated the motility of PANC-1 cells, but differed from PDMF in the
      neutralizing test with antibody against these cytokines. Results of
      characterization and preliminary purification suggest that this factor may be a
      novel motility factor. The above findings suggest that this motility factor may
      play an important role in the invasion and metastasis of pancreatic cancer, and
      complete purification of it will be useful in elucidating the mechanism of
      progression of cancer and designing a strategy for inhibition of invasion and
      metastasis of pancreatic cancer.

PMID- 9174131
TI  - Ovarian cancer cell invasion is inhibited by paclitaxel.
AB  - Overproduction of matrix metalloproteinases (MMPs) and alterations in adhesive
      and migratory behavior are common characteristics of metastatic cancer cells.
      Ovarian cancer is a highly invasive type of malignancy. The effect of the
      antineoplastic drug paclitaxel on human ovarian cancer cell (Ovcar-3) invasion
      was studied using an in vitro invasion assay with reconstituted basement
      membrane. The effect of treatment with paclitaxel was also determined separately
      on certain invasion-associated events, such as the secretion of 72 kDa type IV
      collagenase (gelatinase A/MMP-2), the expression of the tissue inhibitor of
      metalloproteinase-2 (TIMP-2), cell attachment and migration. Ovcar-3 cell
      attachment, migration and in vitro invasion were significantly decreased after
      paclitaxel treatment (P = 0.02, P < 0.01 and P = 0.001, respectively) whereas no
      alteration in the secretion of latent MMP-2 was noted. However, the intracellular
      localization of the immunoreactive protein for MMP-2 was altered in response to
      paclitaxel treatment. Interestingly, paclitaxel increased the appearance of TIMP
      2 protein in culture medium (P = 0.002) but did not change the expression of mRNA
      for TIMP-2 in Ovcar-3 cells. These data show that paclitaxel is an effective
      suppressor of Ovcar-3 cell invasion. It inhibits attachment and migratory
      activities of the cells but also causes a release of TIMP-2 protein into the
      tissue culture medium.

PMID- 9174132
TI  - Interleukin-2 increases intracellular glutathione levels and reverses the growth
      inhibiting effects of cyclophosphamide on B16 melanoma cells.
AB  - Glutathione (GSH) plays an essential role in the metabolism of melanoma. As
      changes in intracellular GSH content can modify the processes of cell
      proliferation and detoxification, this could determine the therapeutic response
      to some cancer treatment strategies. The purpose of this study was to test the
      effects of treatment with interleukin-2 (IL-2), alone and in combination with
      cyclophosphamide (CY), on survival of mice bearing B16 melanoma liver metastases,
      and to determine the influence of these therapeutic agents on the GSH metabolism
      of B16 cells. In the in vivo test system, B16 melanoma liver metastases were
      induced in C57BL/6 mice which were subsequently treated with IL-2, CY and CY plus
      IL-2. Survival time was used to determine the response to treatment. In the in
      vitro system, we evaluated the effects of IL-2, acrolein (an active metabolite of
      CY responsible for GSH depletion) and acrolein plus IL-2 on GSH levels and
      proliferation of B16 melanoma cells. Results indicated that, in vivo, all
      treatments increased mouse survival times with respect to control mice. However,
      the addition of IL-2 to CY therapy decreased survival time compared with
      treatment with CY alone. In vitro, whereas acrolein produced a GSH depletion and
      inhibited B16 cell proliferation, IL-2 increased GSH content and cell
      proliferation rate compared with untreated cells. Moreover, addition of IL-2 to
      cells preincubated with acrolein increased GSH levels and proliferation with
      respect to acrolein alone. In summary, the data suggest that GSH plays a critical
      role in the growth-promoting effects of IL-2 on B16F10 melanoma cells and in the
      antagonistic effect of IL-2 on CY inhibitory activity on these tumor cells.

PMID- 9174133
TI  - Dominant clones in immortalized T-cell lines from rheumatoid arthritis synovial
      membranes.
AB  - Transformation of human T cells by herpesvirus saimiri allows the production of
      an unlimited number of T cells which express a functional T-cell receptor. In
      this study we transformed four T-cell lines derived from rheumatoid arthritis
      synovial membranes. The transformed T cells were mainly CD4+ and expressed the
      phenotype of activated T cells. They were grown for more than 1 year in the
      absence of mitogen or feeder cells, and three of them could be maintained without
      exogenous IL-2. The presence of viral DNA in the transformed cells was shown by
      in situ hybridization with a probe from the H-DNA region of the virus. No
      infectious virus could be recovered from the transformed cells. The relative
      proportion of the 24 different Vbeta families between the four transformed lines
      showed variations that increased with time. In the two T-cell lines transformed
      at an early stage of culture, the Vbeta2 family was maintained at about 10%. The
      dominant Vbeta2 clones that previously have been characterized in the patient
      were found in all transformed T-cell lines. We have thus shown the feasibility of
      obtaining transformed T cells from synovial membranes. They contain the dominant
      clones that are considered of potential importance for the disease, permitting
      further functional studies.

PMID- 9174134
TI  - Biochemical analysis of plasma-soluble invariant chains and their complex
      formation with soluble HLA-DR.
AB  - The invariant chain (CD74) is preferentially localized in the cytoplasm and
      regulates the loading of exogenous derived peptides into HLA class II
      heterodimers. In addition, a small proportion of CD74:class II complexes is also
      expressed on the cell surface. We identified and quantified soluble CD74 (sCD74)
      molecules in the plasma and sCD74:sHLA-DR complexes by ELISA. EDTA plasma samples
      from 86 healthy probands were analyzed. sCD74 could be detected in all samples
      with a mean concentration of 1.14 relative units +/- 1.04 SD (range 0.17-4.31).
      Approximately 10% of the samples had increased amounts of sCD74 (>3.0 relative
      units). Complexes of sCD74 and sHLA-DR were detected in all samples and their
      quantities were positively correlated (r=0.83, p<0.001) with the sCD74
      concentrations. SDS-PAGE analysis of plasma samples with high sCD74
      concentrations (>3.0 relative units) revealed four isoforms of sCD74 with
      molecular weights of 45, 43, 35, 31 kDa corresponding to known sizes of
      intracellular CD74. However, only molecular weights of the 45 and 43 kDa isoforms
      of sCD74 are found complexed with sHLA-DR. Our data demonstrate, that CD74
      molecules are present in their soluble form in the plasma of healthy probands and
      form complexes with soluble HLA-DR molecules.

PMID- 9174135
TI  - DNA typing of human platelet antigen systems 1, 2, 3 and 5 in B-lymphoblastoid
      cell lines of the International Histocompatibility Workshop.
AB  - Alloimmunization against human platelet antigens (HPA) can cause thrombocytopenia
      in different clinical settings, including neonatal alloimmune thrombocytopenia,
      post transfusion purpura, and refractoriness to platelet transfusion. Recently,
      DNA based methods have been described for analysis of the polymorphism of the
      human platelet antigens. However, until now, no reference material for
      standardization purposes is available. We thus determined the DNA polymorphism of
      the human platelet antigen (HPA) systems 1, 2, 3 and 5 in B-lymphoblastoid cell
      lines collected for the International Histocompatibility Workshops. DNA typing of
      the HPA systems was done by PCR amplification with sequence-specific primers (PCR
      SSP). A new enzyme (AmpliTaq Gold) was introduced to enhance the specificity of
      the PCR. We present a panel of five B-lymphoblastoid cell lines, representing all
      heterozygous and homozygous genotypes of the tested HPA systems. This work thus
      provides the reference material required for DNA based diagnosis of human
      platelet antigens.

PMID- 9174136
TI  - Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I
      chain-related gene A): allele frequency data in the nine population groups
      Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and
      Italian.
AB  - We recently identified a trinucleotide repeat polymorphism, (GCT)n, within the
      transmembrane (TM) segment of the human MHC class I MICA gene (MHC class I chain
      related gene A). Five distinct alleles (A4, A5, A5.1, A6, A9) corresponding to 4,
      5, 5 with one nucleotide insertion, 6 and 9 repetitions, respectively, have been
      detected in various HLA-homozygous B cell lines. Here we present allele
      frequencies for this trimeric short tandem repeat (STR) in 604 unrelated
      individuals collected from nine human populations (Japanese, Northern Han, Hui,
      Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian) determined using
      the polymerase chain reaction (PCR) combined with fluorescent-based automated
      fragment detection technology. All alleles were present in each population, but
      allelic distributions varied from one population to another. No new alleles (such
      as A7 or A8) were identified. The evolutionary and structural significance of
      these data as well as the potential application to forensic medicine is
      discussed.

PMID- 9174137
TI  - Sequencing-based typing of HLA-A locus using mRNA and a single locus-specific PCR
      followed by cycle-sequencing with AmpliTaq DNA polymerase, FS.
AB  - The large number (59) of alleles now known at the HLA-A locus is a serious
      challenge to the existing methods for HLA typing, including many of the DNA based
      methods. Here, we describe a sequencing-based typing (SBT) protocol for typing of
      HLA-A alleles using a single A-locus-specific PCR. This reaction amplifies an 824
      base pair product from cDNA, prepared from mRNA, covering exons 1-3 and most of
      exon 4. This product allows identification of all possible combinations of two
      alleles from this locus. The sequencing strategy used for allele assignment
      contains several improvements compared to those previously published. The enzyme
      AmpliTaq DNA Polymerase, FS, used, combines high-quality sequencing, i.e. long
      reads, low background, and uniform peak heights making the identification of
      heterozygous positions very reliable in a fast and easy protocol developed by
      determining the optima for a number of variables. Thus, this strategy meets most
      of the requirements for the use of sequencing in HLA typing. Furthermore, this
      method is very flexible. The use of a PCR primer-pair tailed with the recognition
      sites for two different sequencing primers allows the application of the same
      sets of fluorescent-labelled sequencing primers regardless of the amplified
      locus. Thus, the protocol can very easily be extended to cover the B- and C-locus
      too, simply by adding PCR reactions specific for these loci to the protocol.
      Using this protocol, we investigated a total of 65 cell lines and clinical
      samples, many of the latter chosen from samples difficult to type by serology.
      Our method gave in all cases unambiguous results and proved functional for work
      requiring the highest resolution.

PMID- 9174138
TI  - Molecular genetic analysis of HLA class II alleles in Japanese patients with
      melanoma.
AB  - Distribution of HLA-DQA, -DQB and -DPB alleles in ninety-six Japanese patients
      with melanoma was analyzed using the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method, and the association between
      clinical parameters and the presence of certain HLA class II alleles
      investigated. The frequency of HLA-DQB1*0302 was increased, while those of
      DQA1*0101(04), -DQA1*0401 and DRB1*0802 were decreased in melanoma patients
      compared with controls. Moreover, the frequency of HLA-DQA1*0103 in patients with
      acral lentiginous melanoma was increased compared with controls. However, none of
      these HLA class II alleles showed significant positive or negative associations
      after correction of the P value. In addition, there was no correlation between
      these antigens and clinical parameters. These results indicate that HLA class II
      alleles may not contribute to a strong susceptibility to melanoma in the
      Japanese.

PMID- 9174129
TI  - Technical considerations for studying cancer metastasis in vivo.

PMID- 9174139
TI  - Comparison of DRB sequence-based typing using different strategies.
AB  - Sequence-based typing (SBT) has become an important tool in the identification of
      HLA alleles. In this study a comparison was made between SBT of DRB1/3/4/5
      alleles performed in two laboratories each using a different strategy for SBT.
      The laboratories in Utrecht and in Maastricht performed direct sequencing of PCR
      amplified genomic DNA from 30 selected samples. Primers and conditions for PCR
      amplification were different. Sequencing was either performed with T7 polymerase,
      using internal sequencing primers, or with cycle sequencing using an M13 tailed
      system. Two different automated DNA sequencers were used; the ALFexpress from
      Pharmacia and Applied Biosystems 373A. We concluded that nor the method of
      sequencing nor the sequencing machine influences typing results. However the PCR
      reaction used for generating template DNA is the most critical step. Different
      primers and different conditions can lead to false negative reactions. The fact
      that these false negative reactions can occur with different alleles in different
      combinations but not in all, implicates that extensive quality control is needed
      to assure correct typing results.

PMID- 9174140
TI  - The HLA system in the population of Mongolia.
AB  - The frequencies of HLA-A, B, C and DRB1 alleles and haplotype frequencies for HLA
      A, B, C and A, B, DR loci were studied in 201 healthy unrelated Khalkha
      Mongolians. The most common class I antigens were A24 (25.8%), A2 (23.4%), B61
      (12.6%), B51 (8.5%), Cw10 (14.2%), Cw9 (14.1%), Cw7 (13.3%), Cw1 (11.8%) and Cw6
      (10.2%). A total of 35 DRB1 alleles were identified in this group of samples. The
      most frequent DRB1 allele was DRB1*0301 (11.1%), followed by DRB1*0701 (9.7%) and
      DRB1*1101 (8.5%). One novel DRB1 allele (14MV) and three rare types, DRB1*1111,
      DRB1*1504 and DRB1*1412, recently described in Jews, the Dai minority of China
      and Japanese, respectively, were identified in Mongolians. The phylogenetic tree
      constructed by UPG method put Mongolians in the Northeast Asian cluster. A
      comparison of three locus haplotype distributions with world populations,
      revealed that Mongolians share several characteristics in common with other
      Mongoloids as well as with Caucasoids and Amerindians. The most common A, B and
      DR haplotype in Mongolians, A33-B58-DR3, was shared with Thai, Thai Chinese and
      Singapore Chinese. These data support that unique genetic background of
      Mongolians played a major role in ethnic formation and differentiation of
      Mongoloid populations.

PMID- 9174141
TI  - Molecular analysis of six dog leukocyte antigen class I sequences including three
      complete genes, two truncated genes and one full-length processed gene.
AB  - We have isolated six distinct dog leukocyte antigen (DLA) class I sequences. An
      additional functional nonclassical class I gene, DLA-79, was characterized
      previously. This brings the number of isolated canine class I sequences to seven.
      These seven loci account for nearly all class I sequences detected in genomic DNA
      by Southern blotting. With approximately seven members, the class I gene family
      in dog is considerably less complex than in either human or mouse. Three of the
      six sequences described in this article contain complete class I genes. These
      genes have the typical arrangement of exons and introns, and their predicted
      protein sequences have the features expected of expressed class I molecules. Two
      sequences contain truncated genes. These genes, having only partial class I
      homology and disruptive mutations, are clearly nonfunctional. The remaining locus
      contains a full-length processed gene which is unique among characterized class I
      loci. Sequence comparisons were performed to examine evolutionary relationships
      among the family members. Two sequences, DLA-64 (complete) and -53 (truncated),
      appear to be chimeras presumably formed by interlocus recombination. Using the
      reverse transcription-polymerase chain reaction, mRNA originating from each of
      the three complete genes was identified in canine peripheral blood leukocytes.
      DLA-79 specific transcripts were identified previously. Thus, each of the four
      complete canine class I genes is transcribed in vivo.

PMID- 9174142
TI  - HLA-B*5603: sequence of a novel hybrid allele comprising B*56 and B*4601
      segments.

PMID- 9174143
TI  - Frequency of HLA-B27 subtypes in a Danish population and in Danish patients with
      ankylosing spondylitis.
AB  - Polymerase chain reaction in combination with sequence-specific oligonucleotide
      probes were used to analyze nine HLA-B27 subtypes among 51 healthy HLA-B27
      positive Danish blood donors and 30 Danish HLA-B27 positive patients with
      ankylosing spondylitis (AS). In the group of healthy Danes we found two subtypes,
      B*2705 (90.2%) and B*2702 (9.8%), however, among the AS patients only the B*2705
      subtype was detected. We did not find a significant evidence for associations
      between AS and a particular HLA-B27 subtype in a Danish population.

PMID- 9174144
TI  - MICA gene and ankylosing spondylitis: linkage analysis via a transmembrane
      encoded triplet repeat polymorphism.
AB  - In order to address the possibility that the MICA gene located 47 kb upstream
      from HLA-B is involved in the pathogenesis of ankylosing spondylitis (AS), we
      have investigated microsatellite polymorphism in the transmembrane region of MICA
      in Caucasian patients with AS. The microsatellite allele consisting of 4
      repetitions of GCT/AGC was present at significantly higher frequency in the
      patient group (Pc<0.0000001) than in the ethnically matched control group.
      However, the frequency of the (GCT/AGC)4 allele was significantly low in the B27
      positive patients than in the B27-positive healthy controls (Pc=0.0145). These
      observations suggest that B27 itself remains the primary genetic marker for AS,
      although the significantly dissimilar phenotype frequency of the (GCT/AGC)4
      allele in B27-positive patients and healthy individuals may reflect the existence
      of other genetic factor(s) in the HLA-B27 haplotype involved in the development
      of AS.

PMID- 9174146
TI  - Six new DPB1 alleles identified in a study of 1,302 unrelated bone marrow donor
      recipient pairs.
AB  - Six new DPB1 alleles were identified by PCR-SSOP methodologies in the course of a
      retrospective study of the role of HLA matching in the outcome of unrelated donor
      bone marrow transplantation. Sequencing confirmed that five of these alleles
      (DPB1*5901, *6801, *7101, *7201, and *7301) represent novel combinations of
      previously described sequence motifs in the variable regions of DPB1; the sixth
      (DPB1*7001) appears to result from a novel point mutation. These data support
      previous observations which suggest that multiple mechanisms, including segmental
      exchange and mutation, appear to be responsible for generating sequence diversity
      at the DPB1 locus. The extremely low discrepancy rate of 0.1% between the two
      laboratories which typed the samples, and the ability to predict the new
      sequences from probe hybridization patterns, indicate that SSOP is an accurate
      and efficient method for studying polymorphism at DPB1.

PMID- 9174145
TI  - Sequence of a new HLA-B7 variant, B*0707, that differs from the common B*0702
      allele by one single residue in the peptide binding groove.

PMID- 9174147
TI  - A novel allele, DQB1*0307, in a West African family.

PMID- 9174148
TI  - HLA class I genotyping by cDNA sequence of a Vietnamese family expressing a weak
      B46 antigen.
AB  - Serological heterogeneity in HLA-B46 antigens has been described. Previous
      studies have identified B*4601 as the allele encoding the "strong" B46 antigen
      found in Chinese populations. Serological characterization of a Vietnamese family
      revealed a "weak" B46 antigen. Complementary DNA for the HLA-A, B and C alleles
      of three family members were cloned and the coding regions sequenced. The allele
      encoding the weak B46 antigen has the same coding sequence as B*4601,
      demonstrating that the antigenic differences are not due to polymorphism in the
      amino acid sequence of the HLA-B heavy chain. The recently described HLA-B*1525
      and HLA-Cw*0403 alleles were also found to segregate in this Vietnamese family.

PMID- 9174149
TI  - A novel HLA DRB1 allele (DRB1*0309).

PMID- 9174150
TI  - Identification of a novel HLA-B allele (B*4202) in a Saudi Arabian family with
      Behcet's disease.
AB  - A new HLA-B antigen, tentatively called HLA-B42AND, was identified as a B42
      serologic variant in a Saudi Arabian family. DNA sequencing analysis of the
      second and third exon of this new B allele revealed that B42AND was identical to
      B*4201 except for a single T to C substitution at position 97 of exon 2. This
      substitution results in histidine (CAC) at codon 9 in B42AND instead of tyrosine
      (TAC) in B*4201. The antigen frequency of B42AND in a Saudi Arabian population
      was around 10%. This novel B42AND has officially been named HLA-B*4202.

PMID- 9174151
TI  - A novel DRB1 allele (DRB1*0815) defined in an Australian Aborigine.

PMID- 9174152
TI  - HLA-DQB1*0304-DRB1*0408 haplotype associated with insulin-dependent diabetes
      mellitus in populations in the eastern Baltic region.
AB  - The rare HLA-DQB1*0304 allele was found increased among IDDM patients in the
      populations of the eastern Baltic region. Its frequency among IDDM patients was
      4.5% (20/443) compared to 1.1% (9/853) in healthy controls in the combined series
      of Estonian, Latvian and St. Petersburg Russian populations (P=0.0001). HLA
      DQB1*0304 in these populations was associated with DRB1*0408, and the haplotype
      was further characterized by a B35 allele and a typical combination of
      microsatellite markers from the TNF gene region. The result is compatible with
      the significance of the 57th amino acid in the DQ beta-chain but also emphasizes
      the importance of alleles in other HLA loci adjacent to DQ in the determination
      of IDDM susceptibility.

PMID- 9174153
TI  - Polymorphisms of tumor necrosis factor receptor 2 are not associated with insulin
      dependent diabetes mellitus or Graves' disease.
AB  - Insulin-dependent diabetes mellitus (IDDM) and Graves' disease (GD) are
      autoimmune endocrinopathies and associated with distinct HLA-DR and -DQ alleles
      as well as several tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta)
      alleles. TNF-alpha and TNF-beta interact with TNF receptor (TNF-R), of which two
      subtypes have been described: TNF-R1 and TNF-R2. We investigated TNF-R2 alleles
      in 90 patients with IDDM, 101 with GD and 70 healthy controls. Genomic DNA was
      amplified with specific flanking primers for the untranslated 3' region of TNF
      R2. SSCP analysis revealed two alleles by different fragment patterns: TNF-R2*1
      and TNF-R2*2. Patients with IDDM or Graves' disease and controls did not differ
      significantly: TNF-R2*1/*1:IDDM(8%)/GD(2%)/KO(4%); TNF
      R2*2/*2:IDDM(34%)/GD(48%)/KO(42%), heterozygosity TNF
      R2*1/*2:IDDM(58%)/GD(50%)/KO(54%) (IDDM vs KO: P=0.46, chi2=1.57; GD vs KO:
      P=0.59, chi2=1.05). In conclusion, the studied polymorphism of TNF-R2 was
      associated with neither IDDM nor GD in a German population.

PMID- 9174154
TI  - Nucleotide sequence of HLA-B*5505, which expresses a unique HLA class I
      polymorphism.

PMID- 9174155
TI  - Nucleotide sequence analysis of an HLA-B47 variant (HLA-B*4702).

PMID- 9174156
TI  - Nomenclature for factors of the HLA system, update January/February 1997. WHO
      Nomenclature Committee for factors of the HLA System.

PMID- 9174157
TI  - Eva Klein: the Ruggero Ceppellini lecturer, 1997.

PMID- 9174158
TI  - African-American HLA class II allele and haplotype diversity.
AB  - Molecular genetic techniques were used to type nine loci in the HLA class II
      region in 241 unrelated African-Americans from New York City (NYC). Several
      effects attributable to recent genetic admixture were evident: the number of
      distinct class II alleles and haplotypes was larger in the African-Americans than
      in people of African or European origin, the allele frequencies were more
      consistently even, and linkage disequilibrium was present across the entire class
      II region. The African-American DRB1 allele frequencies almost always fell
      between frequencies among samples from northern Europe and the Gambia, two
      possible founding populations. The exceptions are attributed to the contribution
      of other genetically dissimilar African groups to the African-American gene pool.
      DRB1 allele frequencies (specifically DRB1*1501) and some haplotypes of DRB1-DPB1
      were different in our NYC and the 11th International Histocompatibility Workshop
      (IHW) samples of African-Americans. The high level of allele and haplotype
      diversity found in African-Americans has important implications for the
      construction of pools of unrelated potential donors for tissue transplantation.

PMID- 9174159
TI  - Molecular cloning and functional characterization of the human cytosolic malic
      enzyme promoter: thyroid hormone responsiveness.
AB  - We report the structural and functional features of the 5'-flanking region of the
      human cytosolic malic enzyme (ME) gene. A 2.2-kb subclone, comprising 1.5 kb
      upstream of the translation initiation codon, the first exon, and 0.7 kb of
      flanking intronic region, was sequenced and mapped to chromosome 6. The proximal
      promoter region is rich in G + C, lacks TATA or CCAAT boxes, and shows multiple
      transcription start sites, the major one 106 nucleotides upstream the ATG codon.
      Sequences -59/-13 and -137/-103 conferred maximal promoter activity. Deletional
      analysis revealed the presence of two regions positively regulated by 3,5,3'
      triiodo-L-thyronine (T3). The proximal region confers the strongest T3
      inducibility to the human ME as well as to a heterologous promoter. Thyroid
      hormone receptor beta (TRbeta) binds to an inverted palindromic T3 response
      element (TRE) at position -105/-87 in a manner that is prevented by T3. Nuclear
      extracts or in vitro-translated retinoid acid receptor alpha (RXR alpha) shifted
      the TRbeta retarded band to slower-mobility complexes, which are unaffected by
      T3. In the absence of T3, overexpression of TRbeta repressed the ME promoter
      activity, most probably, through binding of TRbeta homodimers to the TRE. Thus,
      T3 seems to control ME transcription by inducing the dissociation of TRbeta
      homodimers and the functional activation of liganded heterodimers.

PMID- 9174160
TI  - Differential regulation of major surface promoter in hepatitis B virus.
AB  - The major surface promoter of human hepatitis B virus can produce three distinct
      groups of S transcripts. The initiation sites of these transcripts are in close
      proximity. Encompassing the ATG for the middle surface protein, the largest S
      transcript (+1) encodes the middle surface protein whereas the other two (+20 and
      +31) can only code for small surface protein. Sequence analysis does not reveal
      any TATA element. In this study, we employ deletion, linker scanning, and linker
      insertion analyses to study systematically the sequence requirements for the
      initiations of all three transcripts and their upstream regulatory sequences. Our
      study reveals that the sequence downstream of -16 is sufficient for precise
      initiation of all three groups of S transcripts. The 3' boundary of minimal
      promoter element is +15 for the +1 transcript, whereas it is +39 for both +20 and
      +31 transcripts. Furthermore, there are distinct sequence requirements for the
      initiations of three groups of S transcripts. The sequences from -17 to -10 and
      from -1 to +7 are required for the initiation of +1 transcript, the sequence from
      +16 to +39 is essential for the +20 transcript, and the sequences from -17 to -10
      and from +24 to +39 are required for the + 31 transcript. Our results also
      suggest that the transcription initiations of major surface promoter may be
      mediated in part by initiators. The initiations of these three groups of S
      transcripts are under differential regulation. The region from -39 to -16
      containing both negative and positive regulatory elements selectively regulates
      the transcription levels of the two major S transcripts. Most notably, mutation
      of the sequence from -17 to -10, which contains a Sp1 site, leads to an increase
      in the imprecise initiation at +1 site and depresses the initiation of +20 and,
      to a greater extent, +31 transcript. The relevance of differential regulation of
      major surface promoter to the varied production of different surface protein
      isoforms in viral life cycle is discussed.

PMID- 9174161
TI  - The human homeodomain protein OTX2 binds to the human tenascin-C promoter and
      trans-represses its activity in transfected cells.
AB  - Homeodomain-containing proteins mediate many transcriptional processes in
      eukaryotes during development. Recently, mammalian homeodomain proteins involved
      in the anterior head formation have been discovered, but their effect on gene
      transcription has never been investigated. Here we report on the ability of the
      human homeodomain protein OTX2 to bind with high affinity to a target sequence
      present in the promoter of the gene encoding the human extracellular matrix
      protein tenascin-C and to repress its transcriptional activity in transiently
      transfected cells.

PMID- 9174162
TI  - Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the
      activation of the liver-specific protein C gene.
AB  - We have previously characterized the functional cis elements of the protein C
      promoter. One hepatocyte nuclear factor-1 (HNF-1) site, three HNF-3 sites, and at
      least two NF-I sites have been identified within the 140-bp basal transcriptional
      unit of this promoter. Here we present evidence that either HNF-1alpha or HNF-3
      can cooperate with each other in binding to their cis elements. The results from
      the co-transfection assays in HeLa cells showed a novel synergistic
      transactivation between HNF-1alpha and HNF-3. Our data further indicate that the
      unique overlapping of the HNF-3 sites, the specific spatial relationship of the
      sites, and the co-activator C/EBP all contributed to the synergistic interaction.
      Although NF-I itself has a weak transactivating effect, it apparently coordinates
      the transactivation complex formation. NF-I can synergistically enhance the
      transactivation of HNF-1alpha or HNF-3. Taken together, the combinatorial
      interplay of HNF-1alpha, HNF-3, and NF-I make a significant contribution to the
      activation of the liver-specific protein C gene.

PMID- 9174163
TI  - Subcellular distribution of Xenopus XEL-1 protein, a member of the neuron
      specific ELAV/Hu family, revealed by epitope tagging.
AB  - Drosophila and vertebrate elav/Hu genes are involved in the development and the
      maintenance of the nervous system. They all encode proteins that contain three
      RNA recognition motifs (RRM) and are thus expected to play a role in RNA
      metabolism. Drosophila ELAV and RBP9 proteins were reported to be exclusively
      distributed in nuclei of neurons, whereas known human Hu proteins display a
      bipartite nuclear and cytoplasmic distribution. We have previously isolated a
      member of this family in Xenopus, Xel-1, that is exclusively expressed in neural
      tissues from the early tailbud stage onward. In the present study, we report on
      the subcellular distribution of XEL-1 protein using myc epitope tagging, a
      strategy allowing the study of a single member of the ELAV/Hu family. We show
      that the subcellular distribution of exogenous XEL-1 protein in neural tissues
      depends on developmental stages. In the neural tube at the neurula stage, where
      endogenous Xel-1 is not expressed, exogenous tagged XEL-1 protein is localized in
      both the nucleus and the cytoplasm. At the tailbud stage, where endogenous Xel-1
      is expressed, exogenous tagged XEL-1 protein is localized essentially in the
      cytoplasm of neural tube cells. In contrast, exogenous Drosophila ELAV protein
      localizes to the nucleus at all stages in Xenopus embryos. The variability in the
      subcellular localization of ELAV/Hu proteins in different species may have
      functional implications.

PMID- 9174164
TI  - Comparison of mRNA expression of two regulators of G-protein signaling,
      RGS1/BL34/1R20 and RGS2/G0S8, in cultured human blood mononuclear cells.
AB  - RGS1 and RGS2 are members of a new class of regulators of G-protein signaling
      identified by their selective mRNA expression either in phorbol ester (TPA)
      stimulated human B lymphocytes (RGS1/1R20/BL34) or in blood mononuclear cells
      treated with the T-cell lectin concanavalin A (ConA) and cycloheximide
      (RGS2/G0S8). The RGS1 gene shows low basal mRNA expression in freshly purified
      blood mononuclear cells, which increases upon incubation for a day. In contrast,
      RGS2 initially shows high basal levels of mRNA expression, which subsequently
      decrease. Expression of both genes increases in response to ConA, with RGS2 mRNA
      levels increasing briskly to a maximum between 0.5 and 1 hr and decreasing to
      baseline by 6 hr, whereas the RGS1 mRNA increase is delayed reaching a maximum
      between 1 and 2 hr. RGS1 mRNA levels increase much more in response to a protein
      kinase C activator (TPA), than to a calcium ionophore (ionomycin), whereas the
      opposite is true for RGS2. We suggest that ConA elevates RGS2 on the basis of its
      ability to increase intracellular calcium, and that RGS2 may be involved in the
      regulation of intracellular calcium. The distinction between RGS1 and RGS2 is
      further emphasized by studies indicating that recombinant RGS2 does not bind in
      vitro to two members of the G(i) subfamily of G-protein alpha-subunits for which
      recombinant RGS1 has high affinity.

PMID- 9174165
TI  - Identification of the promoters for the human and murine protective
      protein/cathepsin A genes.
AB  - Protective protein/cathepsin A (PPCA) is a lysosomal serine carboxypeptidase that
      forms a complex with beta-galactosidase and neuraminidase. Its deficiency in
      humans leads to the lysosomal storage disorder galactosialidosis (GS). The
      pathologic manifestations in patients relate primarily to the severe deficiency
      of neuraminidase, and the physiological significance of cathepsin A activity
      remains unclear. The mouse model of GS, which closely resembles the human
      phenotype, shows that cells from numerous tissues, especially the central nervous
      system (CNS), are affected by this disease. To study the site and level of
      expression of PPCA mRNA in murine and human tissues, we analyzed the promoter
      regions of the corresponding genes. Their 5' genomic regions were strikingly
      similar in both organization and sequence. A single 1.8-kb PPCA transcript is
      present in humans, whereas mouse tissues have a major 1.8-kb and a minor 2.0-kb
      transcript, both of which are differentially expressed. These two mouse mRNA
      species differ only in their 5' untranslated region (UTR). The larger mRNA,
      unique to mouse, is transcribed from an upstream TATA-box-containing promoter,
      which is absent in the human gene. The downstream promoter, which transcribes the
      1.8-kb mRNA common to human and mouse, has characteristics of housekeeping gene
      promoters and contains putative Sp1 binding sites and three USF/MLTF sequences.
      In vitro studies demonstrated that expression from the downstream promoter is
      higher than that from the upstream murine-specific promoter. In situ
      hybridization of mouse tissue sections identified regions of the brain that
      preferentially express the 2.0-kb transcript. Our results imply that PPCA mRNA
      distribution and regulation in murine tissues differs from that in human tissues.

PMID- 9174166
TI  - Somatic transgene immunization with DNA encoding an immunoglobulin heavy chain.
AB  - A plasmid DNA containing a chimeric immunoglobulin heavy-chain gene with tissue
      specific promoter and enhancer elements was used as a model system to study the
      events triggered by a single intraspleen DNA inoculation in adult C57Bl/6 mice. A
      single intraspleen inoculation was followed in a week by secretion of transgene
      immunoglobulins and production of immunoglobulin M (IgM) anti-immunoglobulins.
      Their kinetics of serum appearance were almost superimposable. While anti
      immunoglobulin antibodies remained detectable for over 6 months, transgene
      immunoglobulins disappeared after 3-4 weeks. However, transgene mRNA was detected
      in the spleen for 4 months. A multiplex polymerase chain reaction (PCR) analysis
      on splenic genomic DNA 17 days after inoculation demonstrated that the transgene
      was integrated in the host chromosomal DNA. The nucleotide sequence of the
      rearranged VDJ region from splenic genomic DNA was identical to that of the
      parental plasmid DNA, hence ruling out that hypermutation had occurred. A booster
      injection of immunoglobulin encoded by the transgene on day 200 elicited a
      typical secondary immune response with IgG1 and IgG2b antibodies. These results
      demonstrate that a single inoculation of an immunoglobulin heavy-chain DNA
      targeted to spleen lymphocytes leads to spontaneous integration of the transgene
      into the host DNA, and that this is sufficient to initiate immunity and establish
      immunologic memory. Our data also show that minute amounts (<100 ng/ml) of an
      endogenously produced protein secreted in the microenvironment of a lymphoid
      tissue generate immunity and establish immunologic memory rather than tolerance.

PMID- 9174168
TI  - H3.3A variant histone mRNA containing an alpha-globin insertion: modulated
      expression during mouse gametogenesis correlates with meiotic onset.
AB  - Replacement-variant H3.3 histones have been isolated and sequenced in different
      eukaryotes, but no functional H3.3A gene has been characterized in the mouse so
      far. We have cloned an H3.3A cDNA from a mouse fetal ovary library,
      differentially screened with testis versus somatic cDNA probes. We showed this
      gene contains a region homologous to the reverse and complementary alpha-globin
      gene. We believe such a structure could have been generated by retroposition
      during the evolution of both globin and histone gene families. The sequence
      coding for H3.3A is 76.6% homologous to the mouse H3.3B gene at the nucleotide
      level and differs in only one amino acid at the protein level. The high degree of
      homology between these genes and the H3.3 variant histones from other eukaryotes
      reveals the conservation of these replication-independent class of histones
      throughout evolution. Analysis of gene expression reveals a developmental
      regulation concurrent with meiotic progression, with the highest level of
      transcript detection coincident with meiotic onset during both oogenesis and
      spermatogenesis.

PMID- 9174167
TI  - Molecular cloning and gene expression analysis of PSP94 (prostate secretory
      protein of 94 amino acids) in primates.
AB  - Prostate secretory protein of 94 amino acids (PSP94) has shown the potential to
      be a diagnostic biomarker and a therapeutic agent for prostate cancer. Primates
      have been the main animal models for studying the biology of this molecule. We
      have cloned and analyzed the cDNA and promoter region of PSP94 from baboon (Papio
      anubis). Sequence divergence among baboon, monkey, pig, and human, in both the
      exons and 5'-flanking region indicates rapid evolution of the PSP94 gene. There
      are conserved steroid hormone response elements (SHRE) in the promoter region of
      all three primate species. Multiple, alternative transcripts starting near these
      SHREs and upstream to the TATA box were identified by reverse transcriptase
      polymerase chain reaction (RT-PCR) and rapid amplification of 5'-cDNA ends (5'
      RACE) in primate prostatic tissues. This differential transcription initiation
      may be linked to androgen regulation of PSP94 gene expression. PSP94 transcripts
      were detected by RT-PCR in a wide variety of mucus-secreting tissues. However,
      the alternative transcripts were found only in the prostate. The distribution of
      the PSP94 protein in baboon secretory tissues was also examined by Western blot
      analysis using a polyclonal antibody against the human homolog. A positive
      immunoreactive band was detected, but it was weak, due probably to epitope
      divergence between the two species. In all young, healthy primate animals tested,
      the level of immunoreactive PSP94 in prostate tissues was lower than expected. In
      addition, RT-PCR combined with Southern blot analysis on prostate tissues in
      these animals failed to detect the PSP57 mRNA produced by alternative splicing of
      PSP94 primary transcript. These observations can be explained by the sexual
      immaturity and incomplete prostate development in these young primates. This
      explanation was supported by histological examination of their prostate during
      PSP94 immunohistochemistry.

PMID- 9174169
TI  - Function of untranslated regions in the mouse spermatogenesis-specific gene Tcp10
      evaluated in transgenic mice.
AB  - The mouse Tcp10 genes are transcribed exclusively in male germ cells and display
      multiple 5' and 3' untranslated variations generated by alternative splicing and
      polyadenylation signal usage. To investigate the possible role of untranslated
      sequences in the regulation of these genes, chimeric expression constructs with
      or without endogenous 5' and 3' untranslated sequences were generated and used to
      make transgenic mice. Analysis of these animals showed that the untranslated
      sequences have no effect on the transcription or translation of an attached lacZ
      reporter gene, thereby implying these sequences are dispensible. However, the
      endogenous pattern of polyadenylation site usage was altered when Tcp10 3'
      untranslated sequences were linked to lacZ, indicating that internal coding
      sequence can influence recognition of polyadenylation signals in testis. The
      characteristics of alternative splicing and polyadenylation signal variability
      reflects a common theme of promiscuity in testicular gene expression.

PMID- 9174170
TI  - A competitive mechanism of CArG element regulation by YY1 and SRF: implications
      for assessment of Phox1/MHox transcription factor interactions at CArG elements.
AB  - In the promoters of many immediate early genes, including c-fos, CArG DNA
      regulatory elements mediate basal constituitive expression and rapid and
      transient serum induction. CArG boxes also occur in the promoters of muscle
      specific genes, including skeletal alpha-actin, where it confers muscle-specific
      expression. These elements are regulated, at least in part, by the ubiquitous
      transcription factors serum response factor (SRF) and YY1. The homeobox
      transcription factor Phox1/MHox has also been implicated in regulation of the c
      fos CArG element and is thought to function by facilitating SRF binding to DNA.
      Here, we provide in vitro and in vivo evidence that the mechanism of YY1
      repression of CArG elements results from competition with SRF for overlapping
      binding sites. We describe in detail the binding sites of YY1 and SRF through
      serial point mutations of the skeletal alpha-actin proximal CArG element and
      identify a mutation that dramatically reduces YY1 binding but retains normal SRF
      binding. YY1 competes with SRF for binding to wild-type CArG elements, but not to
      this point mutant in vitro. This mutant is sufficient for muscle-specific
      expression in vivo but is much less sensitive to repression by YY1
      overexpression. We utilized the YY1/SRF competition to address the role of Phox1
      at these elements. Phox1 overexpression did not diminish YY1-mediated repression,
      suggesting that transcriptional activation by Phox1 does not result from enhanced
      SRF binding to these elements. These methods may prove to be useful for assessing
      interactions between other CArG element regulatory factors.

PMID- 9174171
TI  - Isolation of a cDNA encoding a Kex2-like endoprotease with homology to furin from
      the nematode Caenorhabditis elegans.
AB  - A cDNA was isolated from the nematode Caenorhabditis elegans that encodes an
      endoprotease which is a member of the Kex2 family of serine endoproteases.
      Degenerate oligonucleotide primers were designed based on conserved regions
      within the active sites of known Kex2-like endoproteases, and were used for
      reverse transcription-polymerase chain reaction (RT-PCR) of poly(A)+RNA isolated
      from C. elegans. A PCR product was isolated that had homology to the active sites
      of known furin endoproteases, and was used as a probe to screen a C. elegans cDNA
      library. A Kex2-like endoprotease (CelfurPC) which encoded a 692-amino-acid pre
      proendoprotease, was identified. The deduced amino acid sequence for the
      catalytic domain of CelfurPC is homologous to the known Kex2-like endoproteases,
      with strongest structural homology to the furin/PACE4 family. However, all furins
      and PACE4 proteins contain a characteristic cysteine-rich domain, and all furins
      contain a transmembrane domain, neither of which is present in the CelfurPC
      protein. CelfurPC may thus represent a new class of Kex2-like endoprotease.

PMID- 9174172
TI  - Therapeutic efficacies of isoniazid and rifampin encapsulated in lung-specific
      stealth liposomes against Mycobacterium tuberculosis infection induced in mice.
AB  - One recent promising development in the modification of drug formulations to
      improve chemotherapy is the use of a liposome-mediated drug delivery system. The
      efficacies of isoniazid and rifampin encapsulated in lung-specific stealth
      liposomes were evaluated by injecting liposomal drugs and free drugs into
      tuberculous mice twice a week for 6 weeks. Liposome-encapsulated drugs at and
      below therapeutic concentrations were more effective than free drugs against
      tuberculosis, as evaluated on the basis of CFUs detected, organomegaly, and
      histopathology. Furthermore, liposomal drugs had marginal hepatotoxicities as
      determined from the levels of total bilirubin and hepatic enzymes in serum. The
      elimination of mycobacteria from the liver and spleen was also higher with
      liposomal drugs than with free drugs. The encapsulation of antitubercular drugs
      in lung-specific stealth liposomes seems to be a promising therapeutic approach
      for the chemotherapy of tuberculosis.

PMID- 9174173
TI  - Antimicrobial effects of continuous versus intermittent administration of
      carbapenem antibiotics in an in vitro dynamic model.
AB  - In an in vitro dynamic model we compared the antimicrobial effects of two
      carbapenems, imipenem (MIC, 1 microg/ml) and meropenem (MIC, 0.25 microg/ml) on
      Pseudomonas aeruginosa. The antibiotics were administered either as short-time
      infusions once or three times a day or as continuous infusions with steady-state
      levels ranging from 0.5 to 20 microg/ml. From the resulting kill curves the
      period of time until the onset of bacterial death (dt), the rate constant of
      bacterial death (ka), the maximal reduction of CFU (mr), and the period of time
      until bacterial regrowth occurred (tr) were determined. Additionally, the
      occurrence of bacterial resistance during the simulations (rq) and the
      postantibiotic effect (PAE) were recorded. For both investigated carbapenems no
      significant difference in dt, ka, mr, and PAE values between the short-time
      infusions and continuous infusions with steady-state levels above 2 microg/ml
      could be detected. The tr was longest with continuous infusions of over
      approximately 24 h, corresponding to steady-state levels of 3 microg/ml for
      imipenem and 2.5 microg/ml for meropenem. An increase in MIC was observed only
      during continuous infusions with steady-state levels below 2 microg/ml.
      Independent of the chosen method of application and despite the lower MIC of
      meropenem, imipenem was slightly more effective than meropenem.

PMID- 9174174
TI  - SCH 48973: a potent, broad-spectrum, antienterovirus compound.
AB  - SCH 48973 is a novel molecule with potent, selective, antienterovirus activity.
      In assays of the cytopathic effect against five picornaviruses, SCH 48973 had
      antiviral activity (50% inhibitory concentrations [IC50s]) of 0.02 to 0.11
      microg/ml, with no detectable cytotoxicity at 50 microg/ml. SCH 48973 inhibited
      80% of 154 recent human enterovirus isolates at an IC50 of 0.9 microg/ml. The
      antiviral activity of SCH 48973 is derived from its specific interaction with
      viral capsid, as confirmed by competition binding studies. The affinity constant
      (Ki) for SCH 48973 binding to poliovirus was 8.85 x 10(-8) M. In kinetic studies,
      a maximum of approximately 44 molecules of SCH 48973 were bound to poliovirus
      capsid. SCH 48973 demonstrated efficacy in a murine poliovirus model of
      enterovirus disease. SCH 48973 increased the survival of infected mice when it
      was administered orally at dosages of 3 to 20 mg/kg of body weight/day. Oral
      administration of SCH 48973 also reduced viral titers in the brains of infected
      mice. On the basis of its in vitro and in vivo profiles, SCH 48973 represents a
      potential candidate for therapeutic intervention against enterovirus infections.

PMID- 9174175
TI  - Treatment of gastrointestinal cytomegalovirus infection with twice-daily
      foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients
      with AIDS.
AB  - Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were
      included in an open-label study to evaluate the safety, efficacy, and
      pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily
      accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented
      endoscopically, while safety was evaluated clinically by patient reports and
      physical and laboratory observation. The pharmacokinetics of foscarnet was
      evaluated after the first dose and following approximately 20 days of therapy.
      Nine patients (90%) responded histopathologically, nine (90%) responded
      endoscopically, and nine (90%) responded symptomatically to foscarnet therapy.
      Adverse events resulted in discontinuance of medication in the case of one
      patient. The mean maximal concentration was 621 microM following the first dose
      and 687 microM at steady state (P = 0.11). The apparent elimination rate constant
      and elimination half-life were not different between dose 1 and steady state.
      There were no significant changes in foscarnet excretion or renal clearance
      between dose 1 and steady state. The steady-state volume of distribution was 23.4
      liters following the first dose and 19.0 liters at steady state (P < 0.002).
      Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV
      gastrointestinal disease in this study, resulting in endoscopic or histologic
      improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume
      of distribution noted at steady state compared to single-dose administration are
      readily explained by study design, known information about foscarnet
      pharmacokinetics, and changes in body weight and creatinine clearance in the
      patients.

PMID- 9174176
TI  - Effects of drugs on 2',3'-dideoxy-2',3'-didehydrothymidine phosphorylation in
      vitro.
AB  - Drugs commonly administered to patients infected with the human immunodeficiency
      virus (HIV) have been studied for their propensity to alter the intracellular
      phosphorylation of the anti-HIV nucleoside analog stavudine (2',3'-dideoxy-2',3'
      didehydrothymidine; d4T) in peripheral blood mononuclear cells (PBMCs) and U937
      cells in vitro. PBMCs isolated from the blood of healthy volunteers were
      stimulated by the mitogen phytohemagglutinin (10 microg/ml) for 72 h. Stimulated
      PBMCs (3 x 10(6) cells/plate) were then incubated with [3H]d4T (0.65 microCi; 3
      microM) and either acyclovir, dapsone, ddC, ddI, fluconazole, foscarnet,
      ganciclovir, itraconazole, lobucavir, ranitidine, ribavirin, rifampin,
      sorivudine, sulfamethoxazole, trimethoprim, lamivudine (3TC), zidovudine, or
      thymidine (30 and 300 microM) for 24 h. Doxorubicin and drugs showing some
      evidence of inhibition were also studied at 0.3 and 3 microM. Cells were
      extracted overnight with 60% methanol prior to analysis by radiometric high
      performance liquid chromatography. Additional data for nine of the drugs were
      obtained by incubation with [3H]d4T in U937 cells for 24 h. The effect of d4T
      (0.2 to 20 microM) on zidovudine (0.65 microCi; 0.018 microCi) phosphorylation
      was also studied. Zidovudine significantly reduced d4T total phosphates in PBMCs
      and U937 cells (in PBMCs to 33% [P < 0.001] and 17% [P < 0.001] of that in
      control cells at 3 and 30 microM, respectively). A small reduction in zidovudine
      phosphorylation was seen with d4T but only at d4T:zidovudine ratios of 100 and
      1,000. Of the other compounds screened, only thymidine, ribavirin, and
      doxorubicin produced inhibition of d4T phosphorylation in both PBMCs and U937
      cells. However, doxorubicin was cytotoxic at 3 microM. The decrease in d4T
      phosphorylation in the presence of ribavirin is consistent with previous findings
      with zidovudine. Although ddC significantly inhibited the phosphorylation of d4T
      in PBMCs, this was not seen in U937 cells, and it is probable that the findings
      in PBMCs are related to mitochondrial toxicity [based on 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide cytotoxicity assay]. The only drugs screened
      which may interfere with d4T phosphorylation at clinically relevant
      concentrations were zidovudine, ribavirin, and doxorubicin.

PMID- 9174177
TI  - Attenuation of gentamicin-induced nephrotoxicity in rats by fleroxacin.
AB  - The effect of fleroxacin on gentamicin-induced nephrotoxicity was evaluated with
      female Sprague-Dawley rats. Animals were injected during 4 or 10 days with saline
      (NaCl; 0.9%), gentamicin alone at doses of 10 and 40 mg/kg of body weight/12 h
      (subcutaneously), fleroxacin alone at a dose of 25 mg/kg/12 h
      (intraperitoneally), or the combination gentamicin-fleroxacin in the same
      regimen. Gentamicin induced a dose- and time-dependent renal toxicity as
      evaluated by gentamicin cortical levels, sphingomyelinase activity in the renal
      cortex, histopathologic and morphometric analysis, blood urea nitrogen and serum
      creatinine levels, and cellular regeneration ([3H]thymidine incorporation into
      DNA of cortical cells). The extent of these changes was significantly reduced
      when gentamicin was given in combination with fleroxacin. Although the mechanisms
      by which fleroxacin reduces the nephrotoxic potential of gentamicin are unknown,
      we propose that the fleroxacin-gentamicin combination enhances exocytosis
      activity in proximal tubular cells, as suggested by the higher excretion of
      urinary enzymes and lower cortical levels of gentamicin observed in animals
      treated with the combination fleroxacin-gentamicin compared with those treated
      with gentamicin alone. The protective effect of fleroxacin on gentamicin
      nephrotoxicity should be investigated further.

PMID- 9174178
TI  - In vitro assessment of gastric mucosal transfer of anti-Helicobacter therapeutic
      agents.
AB  - A novel animal model for studying antibiotic transfer across gastric mucosa was
      developed by using adult rats. Gastric corpus mucosa was mounted in an Ussing
      chamber system and bathed in oxygenated Krebs solution. Metronidazole flux from
      serosa to mucosa (J(S-->M)) was measured over 60 min under basal conditions and
      compared with mucosa-to-serosa flux (J(M-->S)). The effects of varying the
      chamber cross-sectional diameter and of stimulation by histamine and carbachol
      were assessed. Metronidazole J(M-->S) was measured with the mucosal pH at 2.2,
      2.7, 3.2, and 7.4. Amoxicillin J(S-->M) under basal conditions was also measured
      and compared with metronidazole J(S-->M). Metronidazole J(S-->M) was proportional
      to serosal concentration (P < 0.001) under basal conditions, being 3.98 nmol x h(
      1) x cm(-2) with a serosal concentration of 0.2 mmol/liter. Amoxicillin J(S-->M)
      was significantly lower under similar conditions at 0.50 nmol x h(-1) x cm(-2) (P
      < 0.01). Metronidazole J(S-->M) was not significantly different from J(M-->S),
      between chambers of different sizes, or following stimulation. When the mucosal
      pH was changed, J(M-->S) was proportional to the un-ionized concentration on the
      mucosal side (P < 0.001). Therefore, this model shows properties analogous to
      those of human gastric mucosa in vivo, with partitioning of metronidazole on the
      mucosal side according to pH, diffusion of metronidazole across the mucosa in
      both directions, and selectivity for different antibiotics, and it will be useful
      for the study of other therapeutic agents in the treatment of Helicobacter
      pylori.

PMID- 9174179
TI  - Potent and selective inhibition of human immunodeficiency virus type 1
      transcription by piperazinyloxoquinoline derivatives.
AB  - We have found novel piperazinyloxoquinoline derivatives to be potent and
      selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication
      in both acutely and chronically infected cells. 8-Difluoromethoxy-1-ethyl-6
      fluoro-1,4-didehydro-7-[4-(2-met hoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3
      carboxylic acid (K-12), the most potent congener of the series, completely
      inhibited HIV-1 replication in acutely infected MOLT-4 cells at a concentration
      of 0.16 to 0.8 microM without showing any cytotoxicity. The compound completely
      suppressed tumor necrosis factor alpha (TNF-alpha)-induced HIV-1 expression in
      latently infected cells (OM-10.1) and constitutive viral production in
      chronically infected cells (MOLT-4/III(B)) at a concentration of 0.8 microM. K-12
      could also inhibit HIV-1 antigen expression in OM-10.1 and MOLT-4/III(B) cells at
      this concentration. Northern blot analysis revealed that K-12 selectively
      prevented the accumulation of HIV-1 mRNA in MOLT-4/III(B) and TNF-alpha-treated
      OM-10.1 cells in a dose-dependent fashion. It was not inhibitory to HIV-1 Tat or
      the cellular transcription factors NF-kappaB and Sp1, suggesting that the
      piperazinyloxoquinoline derivatives are a group of HIV-1 transcription inhibitors
      with a unique mechanism of action.

PMID- 9174180
TI  - Pharmacokinetic study of praziquantel administered alone and in combination with
      cimetidine in a single-day therapeutic regimen.
AB  - A brief therapeutic regimen of praziquantel, reduced to a single day, has been
      effective for treatment of neurocysticercosis. To study its pharmacokinetic
      characteristics, levels of praziquantel in plasma were determined for eight
      healthy volunteers after the administration of three oral doses of 25 mg/kg of
      body weight given at 2-h intervals, alone and with the simultaneous
      administration of cimetidine. Each volunteer received both regimens in a
      randomized crossover design. Blood samples were taken during a period of 12 h,
      and praziquantel concentration was measured by high-performance liquid
      chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during
      a period of 12 h; they increased 100% when cimetidine was jointly administered.
      Compared with other regimens, the high levels obtained and the longer duration of
      action seem to be advantageous in prolonging the exposure of the parasites to the
      drug and support previous clinical experience showing that the treatment of
      neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with
      the drug still retaining its cysticidal properties. Moreover, simultaneous
      administration of praziquantel and cimetidine could improve further the efficacy
      of the single-day therapy for cysticercosis and other parasitic diseases, such as
      schistosomiasis.

PMID- 9174181
TI  - Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ
      2640.
AB  - The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640,
      against gram-positive and -negative bacteria was compared with those of penems
      and cephalosporins currently available. MICs at which 90% of the isolates are
      inhibited (MIC90s) of the compound for clinical isolates of methicillin
      susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis,
      including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5
      microg/ml, respectively. DU-6681a inhibited the growth of all strains of
      Streptococcus pyogenes and of penicillin-susceptible and -insusceptible
      Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and
      MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and
      Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025
      microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria
      gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU
      6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected
      by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of
      human serum but was decreased under acidic conditions against gram-negative
      bacteria, under alkaline conditions against gram-positive bacteria, and in human
      urine, as was the activity of the other antibiotics tested. The frequency of
      spontaneous resistance to DU-6681a was less than or equal to those of the
      reference compounds. Time-kill curve studies demonstrated the bactericidal action
      of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H.
      influenzae.

PMID- 9174182
TI  - Modeling the response of pneumonia to antimicrobial therapy.
AB  - The response to antimicrobial therapy in patients with pneumonia was assessed by
      using a previously developed pneumonia scoring system. Patients from two
      different clinical trials were evaluated. The first group (n = 22) was treated
      with cefmenoxime. For these patients, doses were adjusted to achieve an area
      under the plasma concentration-versus-time curve (AUC) above the MIC of 140
      microg x h/ml and pneumonia response scores were evaluated retrospectively. The
      second group (n = 21) were treated with either ciprofloxacin (CIP) or ceftazidime
      (TAZ) in a randomized clinical trial. Here, doses were adjusted to achieve AUC
      from 0 to 24 h/MIC values that were > 250 SIT(-1) x h (estimate of the area under
      the curve of inverse serum inhibitory titer versus time) and pneumonia response
      scoring was concurrent. In both studies eradication of the pathogen was
      determined by serial endotracheal cultures and clinical parameters were scored
      daily. A decrease in total score was indicative of an improving clinical
      condition. The percent change in clinical daily score was determined for each day
      of treatment. The rate of clinical response was determined by linear regression
      of the percent change in daily clinical score versus time during the course of
      antimicrobial therapy. Factors predictive of time to eradication were explored by
      interval analysis. Logistic regression was used to determine the earliest time
      point in therapy at which treatment scores predicted outcome. Kruskal-Wallis
      analysis of variance was used for statistical analysis, and significance was
      accepted at P < 0.05. There were no differences in baseline scores at day one for
      the patients treated with different antibiotics (P = 0.58). For patients with
      pathogen eradication, a significant difference between the two studies in time to
      eradication was found: 4.8 days for cefmenoxime-treated patients and 1.4 days for
      CIP- or TAZ-treated patients (P < 0.001). For patients experiencing bacterial
      eradication, the rates of clinical change for cefmenoxime and CIP or TAZ
      treatment were similar (P = 0.77). For patients with organisms that were not
      eradicated, the rates of change were similar (P = 0.14). There was a significant
      difference in the rate of change for patients experiencing eradication compared
      with that for patients in which the organism persisted (P << 0.01). Both
      treatment group and rate were found to be predictive of days to eradication.
      There was a significant difference in the percent change in clinical score on day
      3 of therapy for patients with bacteria that were eradicated versus those with
      persistent organisms (P < 0.01). The percent change was more predictive of
      outcome with each subsequent day. Patients who demonstrated a > or = 10%
      reduction in clinical score after 72 h of treatment had an 88% probability of
      bacterial eradication. The clinical scoring system is a useful tool for modeling
      the response of pneumonia to antimicrobial therapy. The ability to predict
      outcome relatively early in therapy, by using a scoring system of clinical
      parameters which can be routinely monitored, will aid in assessing the response
      to antimicrobial therapy in clinical as well as in research settings.

PMID- 9174183
TI  - Pharmacokinetics of liposomal amphotericin B (Ambisome) in critically ill
      patients.
AB  - The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute
      and chronic side effects of the parent drug. The present study describes the
      pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of
      2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics
      observed in 6 patients treated with amphotericin B deoxycholate at the standard
      dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak
      concentrations (Cmax) and areas under concentration-time curves (AUC) were 8- to
      10-fold greater for patients treated with AmBisome than for patients treated with
      amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median
      Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/ml) and median AUCs exceeded
      those observed with amphotericin B deoxycholate by 9-fold. This was in part
      explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome
      treated patients. The elimination of amphotericin B from serum was biphasic for
      both formulations. However, the apparent half-life of elimination was twofold
      shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a
      significant impact on AmBisome pharmacokinetics as analyzed in one patient. In
      conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001)
      reduces the volume of drug distribution, thereby allowing for greater drug
      concentrations in serum. The low toxicity of AmBisome therefore cannot readily be
      explained by its serum pharmacokinetics.

PMID- 9174184
TI  - Parameters of bacterial killing and regrowth kinetics and antimicrobial effect
      examined in terms of area under the concentration-time curve relationships:
      action of ciprofloxacin against Escherichia coli in an in vitro dynamic model.
AB  - Although many parameters have been described to quantitate the killing and
      regrowth of bacteria, substantial shortcomings are inherent in most of them, such
      as low sensitivity to pharmacokinetic determinants of the antimicrobial effect,
      an inability to predict a total effect, insufficient robustness, and uncertain
      interrelations between the parameters that prevent an ultimate determination of
      the effect. To examine different parameters, the kinetics of killing and regrowth
      of Escherichia coli (MIC, 0.013 microg/ml) were studied in vitro by simulating a
      series of ciprofloxacin monoexponential pharmacokinetic profiles. Initial
      ciprofloxacin concentrations varied from 0.02 to 19.2 microg/ml, whereas the half
      life of 4 h was the same in all experiments. The following parameters were
      calculated and estimated: the time to reduce the initial inoculum (N0) 10-, 100-,
      and 1,000-fold (T90%, T99%, and T99.9%, respectively), the rate constant of
      bacterial elimination (k(elb)), the nadir level (Nmin) in the viable count (N)
      versus-time (t) curve, the time to reach Nmin (t(min)), the numbers of bacteria
      that survived (Ntau) by the end of the observation period (tau), the area under
      the bacterial killing and regrowth curve (log N(A)-t curve) from the zero point
      (time zero) to tau (AUBC), the area above this curve (AAC), the area between the
      control growth curve (log N(C)-t curve) and the bacterial killing and regrowth
      curve (log N(A)-t curve) from the zero point to tau (ABBC) or to the time point
      when log N(A) reaches the maximal values observed in the log N(C)-t curve (I(E);
      intensity of the effect), and the time shift between the control growth and
      regrowth curves (T(E); duration of the effect). Being highly sensitive to the
      AUC, I(E), and T(E) showed the most regular AUC relationships: the effect
      expressed by I(E) or T(E) increased systematically when the AUC or initial
      concentration of ciprofloxacin rose. Other parameters, especially T90%, T99%,
      T99.9%, t(min), and log N0 - log Nmin = delta log Nmin, related to the AUC less
      regularly and were poorly sensitive to the AUC. T(E) proved to be the best
      predictor and t(min) proved to be the worst predictor of the total antimicrobial
      effect reflected by I(E). Distinct feedback relationships between the effect
      determination and the experimental design were demonstrated. It was shown that
      unjustified shortening of the observation period, i.e., cutting off the log N(A)
      t curves, may lead to the degeneration of the AUC-response relationships, as
      expressed by log N0 - log Ntau = delta log Ntau, AUBC, AAC, or ABBC, to a point
      where it gives rise to the false idea of an AUC- or concentration-independent
      effect. Thus, use of I(E) and T(E) provides the most unbiased, robust, and
      comprehensive means of determining the antimicrobial effect.

PMID- 9174185
TI  - Aerosol delivery of liposome-encapsulated ciprofloxacin: aerosol characterization
      and efficacy against Francisella tularensis infection in mice.
AB  - The aerosol delivery of liposome-encapsulated ciprofloxacin by using 12
      commercially available jet nebulizers was evaluated in this study. Aerosol
      particles containing liposome-encapsulated ciprofloxacin generated by the
      nebulizers were analyzed with a laser aerodynamic particle sizer. Mean mass
      aerodynamic diameters (MMADs) and geometric standard deviations (GSDs) were
      determined, and the drug contents of the sampling filters from each run onto
      which aerosolized liposome-encapsulated ciprofloxacin had been deposited were
      analyzed spectrophotometrically. The aerosol particles of liposome-encapsulated
      ciprofloxacin generated by these nebulizers ranged from 1.94 to 3.5 microm, with
      GSDs ranging from 1.51 to 1.84 microm. The drug contents of the sampling filters
      exposed for 1 min to aerosolized liposome-encapsulated ciprofloxacin range from
      12.7 to 40.5 microg/ml (0.06 to 0.2 mg/filter). By using the nebulizer selected
      on the basis of most desirable MMADs, particle counts, and drug deposition,
      aerosolized liposome-encapsulated ciprofloxacin was used for the treatment of
      mice infected with 10 times the 50% lethal dose of Francisella tularensis. All
      mice treated with aerosolized liposome-encapsulated ciprofloxacin survived the
      infection, while all ciprofloxacin-treated or untreated control mice succumbed to
      the infection (P < 0.001). These results suggest that aerosol delivery of
      liposome-encapsulated ciprofloxacin to the lower respiratory tract is feasible
      and that it may provide an effective therapy for the treatment of respiratory
      tract infections.

PMID- 9174186
TI  - In vitro activities of ciprofloxacin and rifampin alone and in combination
      against growing and nongrowing strains of methicillin-susceptible and methicillin
      resistant Staphylococcus aureus.
AB  - We characterized the effects of ciprofloxacin and rifampin alone and in
      combination on Staphylococcus aureus in vitro. The effects of drug combinations
      (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition
      were compared by disk approximation studies and by determining the fractional
      inhibitory concentrations. Bactericidal effects in log-phase bacteria and in
      nongrowing isolates were characterized by time-kill methods. The effect of drug
      combinations was dependent upon whether or not cells were growing and whether
      killing or growth inhibition was the endpoint used to measure drug interaction.
      Despite bactericidal antagonism in time-kill experiments, our in vitro studies
      suggest several possible explanations for the observed benefits in patients
      treated with a combination of ciprofloxacin and rifampin for deep-seated
      staphylococcal infections. Notably, when growth inhibition rather than killing
      was used to characterize drug interaction, indifference rather than antagonism
      was observed. An additive bactericidal effect was observed in nongrowing bacteria
      suspended in phosphate-buffered saline. While rifampin antagonized the
      bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the
      bactericidal effects of rifampin. Each antimicrobial prevented the emergence of
      subpopulations that were resistant to the other.

PMID- 9174187
TI  - Penetration of trovafloxacin into cerebrospinal fluid in humans following
      intravenous infusion of alatrofloxacin.
AB  - A single-dose study was conducted to determine concentrations of trovafloxacin
      (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the
      serum of healthy subjects after intravenous infusion of alatrofloxacin (CP
      116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects
      were administered single doses of alatrofloxacin at a trovafloxacin equivalent of
      300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar
      puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the
      infusion; each subject was sampled at only one time point. Serum samples were
      taken from each subject at the time of CSF collection. A mean concentration of
      5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of
      the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution
      phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common
      adverse events were dizziness, nausea, and rash and were mild or moderate in
      intensity. The potency of trovafloxacin against susceptible organisms, coupled
      with its rapid penetration of CSF following the intravenous administration of
      alatrofloxacin, suggests that it may be useful in the treatment of bacterial
      meningitis in humans.

PMID- 9174188
TI  - Antimicrobial susceptibility of flavobacteria as determined by agar dilution and
      disk diffusion methods.
AB  - A total of 106 clinical isolates of flavobacteria, including 41 isolates of
      Flavobacterium meningosepticum, 59 of Flavobacterium indologenes, and 6 of
      Flavobacterium odoratum were collected from January 1992 to December 1995 from
      patients in Taiwan. The in vitro activities of antimicrobial agents were
      determined concomitantly by the standard agar dilution and disk diffusion
      methods. More than 90% of the flavobacterial isolates were resistant to
      cephalothin, cefotaxime, ceftriaxone, moxalactam, aztreonam, imipenem,
      aminoglycosides, erythromycin, and glycopeptides. The majority of F.
      meningosepticum isolates were susceptible to piperacillin and to minocycline but
      resistant to ceftazidime, with MICs at which 90% of the isolates are inhibited
      being 8, 4, and > 128 microg/ml, respectively. Approximately half of the F.
      indologenes isolates were susceptible to piperacillin, cefoperazone, ceftazidime,
      and minocycline, with MICs at which 50% of the isolates are inhibited being 4,
      16, 8, and 4 microg/ml, respectively. The majority of F. odoratum isolates were
      resistant to all the antimicrobial agents tested except minocycline, to which
      five of six isolates were susceptible. With least-squares regression analysis and
      error rate-bounded analysis methods, the following resistant and susceptible zone
      diameter breakpoints were established: < or = 12 and > or = 17 mm, respectively,
      for piperacillin against F. meningosepticum and F. indologenes; < or = 13 and >
      or = 18 mm, respectively, for ceftazidime against F. meningosepticum and F.
      indologenes, < or = 17 and > or = 21 mm, respectively, for ofloxacin against F.
      indologenes; < or = 16 and > or = 20 mm, respectively, for ciprofloxacin against
      F. meningosepticum. Valid breakpoints for the disk diffusion method could not be
      established for cefoperazone and ofloxacin against F. meningosepticum and for
      minocycline against F. meningosepticum and F. indologenes due to a poor
      correlation coefficient for the regression line or for cefoperazone and
      ciprofloxacin against F. indologenes due to the presence of remarkable error
      rates.

PMID- 9174189
TI  - Pharmacodynamic evaluation of a new glycopeptide, LY333328, and in vitro activity
      against Staphylococcus aureus and Enterococcus faecium.
AB  - The objectives of the present study were to compare the in vitro activity of
      LY333328 (LY) to that of vancomycin (V) alone and in combination with gentamicin
      (G) and rifampin (R) against methicillin-resistant Staphylococcus aureus (MRSA)
      and V-resistant Enterococcus faecium (VREF), by using the killing curve methods.
      In addition, the effect of the inoculum size and protein on LY's activity was
      evaluated by using MICs and killing curves. MICs, MBCs, and killing curves were
      determined with supplemented Mueller-Hinton broth (B), B with albumin (4 g/dl)
      (A), and B with 50% pooled human serum (S). For MRSA, time to 99.9% killing after
      exposure to LY at four times the MIC (4x MIC) was achieved at 0.5 +/- 0 h (mean
      +/- standard deviation) and was significantly faster than that by V (8.54 +/-
      0.10 h; P = 0.001). Against VREF, LY decreased the inoculum by 2.2 log10 CFU/ml
      at 24 h (P = 0.002). With a large inoculum of MRSA, the activity of LY and V at
      4x MIC was decreased compared to that with the standard inoculum (P = 0.0003) and
      regrowth occurred at 24 h. The reduction in the number of CFU per milliliter at
      24 h to 2 log10 CFU/ml was restored by increasing the LY concentration to at
      least 16x MIC. At 24 h, the combinations of LY and G, LY and R, LY and V, and V
      and G were better than either LY or V alone against a large inoculum of MRSA (P =
      0.0002). LY and G achieved 99.9% killing at 1.01 +/- 0.03 h and was more rapid (P
      < 0.007) than all the other regimens studied except for V and G, which achieved
      99.9% killing at 3.59 +/- 0.01 h. Killing curves determined with different media
      against a standard inoculum of MRSA did not demonstrate a significant difference
      between LY and V at 24 h. Time to 99.9% killing was more rapid with LY than with
      V in B, A, and S (P = 0.0002). Times to 99.9% killing by LY in B, A, and S were
      not significantly different from each other. Against VREF, LY killed better than
      V in B, A, or S at 24 h (P = 0.0002). LY in B was more active than LY in A or S
      (P = 0.0002). LY is a new potent glycopeptide with a unique activity profile. It
      has a greater activity than that of V against MRSA and has activity against VREF.
      LY demonstrated synergism in combination with gentamicin against MRSA. LY was
      affected by large inoculum sizes and proteins in time-kill studies. However, the
      effect was compensated for by increasing the drug concentration to 16x MIC.

PMID- 9174191
TI  - Disposition of atovaquone in humans.
AB  - Atovaquone is an antiprotozoal compound with good in vitro stability against
      metabolic inactivation. Previous human studies which did not involve
      radiolabelling had not accounted for a substantial proportion of the dose. The
      possible metabolism of atovaquone in men was examined in a radiolabelling study
      involving four healthy male volunteers. Radioactivity was eliminated almost
      exclusively via the feces. All radioactivity in plasma, urine, and feces was
      accounted for by atovaquone, with no evidence of metabolites. Radiolabelled
      atovaquone was administered to a patient with an indwelling biliary tube after
      surgery. Biliary radioactivity was approximately 10- to 40-fold higher than that
      in plasma and was accounted for by atovaquone. Atovaquone is not significantly
      metabolized in humans but is excreted into bile against a high concentration
      gradient.

PMID- 9174190
TI  - In vitro induction of human immunodeficiency virus type 1 variants resistant to
      2'-beta-Fluoro-2',3'-dideoxyadenosine.
AB  - 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA) is an acid-stable purine
      dideoxynucleoside analog active against a wide spectrum of human immunodeficiency
      virus type 1 (HIV-1) and HIV-2 strains in vitro. F-ddA is presently undergoing a
      phase I clinical trial at the National Cancer Institute. We induced HIV-1
      variants resistant to F-ddA by exposing wild-type HIV-1 (HIV-1LAI) to increasing
      concentrations of F-ddA in vitro. After 18 passages, the virus was fourfold less
      sensitive to F-ddA than HIV-1LAI. Sequence analyses of the passage 18 virus
      revealed changes in three amino acids in the reverse transcriptase (RT)-encoding
      region of the pol gene: P to S at codon 119 (P119S; present in 3 of 13 and 28 of
      28 molecular clones before and after F-ddA exposure, respectively), V179D (0 of
      13 and 9 of 28, respectively), and L214F (9 of 13 and 28 of 28, respectively).
      Drug sensitivity assays using recombinant infectious clones confirmed that P119S
      was directly responsible for the reduced sensitivity of HIV-1 to F-ddA. Various
      infectious clones with single or multiple amino acid substitutions conferring
      viral resistance against nucleoside RT inhibitors, including HIV-1 variants with
      multi-dideoxynucleoside resistance, were generally sensitive to F-ddA. The
      moderate level of resistance of HIV-1 to F-ddA, together with the lack of
      conferment of significant cross-resistance by the F-ddA-associated amino acid
      substitutions, warrants further investigation of F-ddA as a potential antiviral
      agent for use in treatment of HIV-1 infection.

PMID- 9174192
TI  - A complex mutant of TEM-1 beta-lactamase with mutations encountered in both IRT-4
      and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate.
AB  - Escherichia coli GR102 was isolated from feces of a leukemic patient. It
      expressed different levels of resistance to amoxicillin or ticarcillin plus
      clavulanate and to the various cephalosporins tested. The double-disk synergy
      test was weakly positive. Production of a beta-lactamase with a pI of 5.6 was
      transferred to E. coli HB101 by conjugation. The nucleotide sequence was
      determined by direct sequencing of the amplification products obtained by PCR
      performed with TEM gene primers. This enzyme differed from TEM-1 (blaT-1B gene)
      by four amino acid substitutions: Met-->Leu-69, Glu-->Lys-104, Gly-->Ser-238 and
      Asn-->Asp-276. The amino acid susbstitutions Leu-69 and Asp-276 are known to be
      responsible for inhibitor resistance of the IRT-4 mutant, as are Lys-104 and Ser
      238 substitutions for hydrolytic activity of the extended-spectrum beta
      lactamases TEM-15, TEM-4, and TEM-3. These combined mutations led to a mutant
      enzyme which conferred a level of resistance to coamoxiclav (MIC, 64 microg/ml)
      much lower than that conferred by IRT-4 (MIC, 2,048 microg/ml) but higher than
      that conferred by TEM-15 or TEM-1 (MIC, 16 microg/ml). In addition, the MIC of
      ceftazidime for E. coli transconjugant GR202 (1 microg/ml) was lower than that
      for E. coli TEM-15 (16 microg/ml) and higher than that for E. coli IRT-4 or TEM-1
      (0.06 microg/ml). The MICs observed for this TEM-type enzyme were related to the
      kinetic constants Km and k(cat) and the 50% inhibitory concentration, which were
      intermediate between those observed for IRT-4 and TEM-15. In conclusion, this new
      type of complex mutant derived from TEM-1 (CMT-1) is able to confer resistance at
      a very low level to inhibitors and at a low level to extended-spectrum
      cephalosporins. CMT-1 received the designation TEM-50.

PMID- 9174193
TI  - In vitro activity of HSR-903, a new quinolone.
AB  - The in vitro activity of the new fluoroquinolone HSR-903 was compared with those
      of ciprofloxacin, lomefloxacin, sparfloxacin, and levofloxacin. HSR-903 inhibited
      90% of methicillin-susceptible and -resistant Staphylococcus aureus (MRSA)
      clinical isolates at 0.78 and 1.56 microg/ml, respectively, and its activity
      against MRSA was 16-fold higher than those of sparfloxacin and levofloxacin and
      64-fold higher than that of ciprofloxacin. The MICs at which 90% of the isolates
      are inhibited (MIC90s) of HSR-903 for Streptococcus pyogenes and penicillin G
      susceptible and -resistant Streptococcus pneumoniae (PRSP) were 0.10, 0.05, and
      0.05 microg/ml, respectively. Against PRSP, the activity of HSR-903 was 4-fold
      higher than that of sparfloxacin and 32- to 256-fold higher than those of the
      other quinolones. The MIC90 of HSR-903 for Enterococcus faecalis was 0.20
      microg/ml, and HSR-903 was more active than the other quinolones against
      enterococci. The activity of HSR-903 against members of the family
      Enterobacteriaceae and Pseudomonas aeruginosa was roughly similar to that of
      ciprofloxacin and greater than those of the other quinolones. Against Haemophilus
      influenzae, Moraxella catarrhalis, and Helicobacter pylori, HSR-903 was the most
      potent of the quinolones tested. The activity of HSR-903 was not affected by the
      medium, the inoculum size, or the addition of serum, but decreased under acidic
      conditions, as did those of the other quinolones tested. HSR-903 exhibited rapid
      bactericidal action and had a good postantibiotic effect on S. aureus and P.
      aeruginosa. HSR-903 inhibited supercoiling by DNA gyrase from Escherichia coli,
      but it was much less active against human topoisomerase II.

PMID- 9174194
TI  - In vitro and in vivo activities of AM-1155, a new fluoroquinolone, against
      Chlamydia spp.
AB  - The in vitro and in vivo activities of AM-1155, a new quinolone, against
      Chlamydia spp. were investigated. The MIC of AM-1155 for 10 standard strains of
      different Chlamydia spp. and 25 wild-type strains of Chlamydia pneumoniae
      isolated in Japan, which were morphologically different from clinical isolates
      from the United States, ranged from 0.063 to 0.125 microg/ml. Its activity was
      almost the same as those of sparfloxacin and tosufloxacin and was 4 and 16 times
      superior to those of levofloxacin and ciprofloxacin, respectively, but lower than
      those of clarithromycin and minocycline (range for each, 0.016 to 0.031
      microg/ml). The minimal chlamydiacidal concentration of AM-1155 ranged from 0.063
      to 0.125 microg/ml, while those of clarithromycin and minocycline ranged from
      0.016 to 0.031 microg/ml and 0.016 to 0.063 microg/ml, respectively. The
      therapeutic effect of a 7-day course of AM-1155 at doses of 5 and 10 mg/kg of
      body weight administered orally twice daily to mice with experimental Chlamydia
      psittaci pneumonia was excellent, with a 100% survival rate at 21 days after
      infection. The efficacy was equal to those of clarithromycin and minocycline and
      higher than those of ciprofloxacin and ofloxacin.

PMID- 9174195
TI  - The microbicidal agent C31G inhibits Chlamydia trachomatis infectivity in vitro.
AB  - Safe and effective vaginal microbicidal compounds are being sought to offer women
      an independent method for protection against transmission of sexually acquired
      pathogens. The purpose of this study was to examine the efficacy of two
      formulations of one such compound, C31G, against Chlamydia trachomatis serovar E
      alone, its host epithelial cell (HEC-1B) alone, and against chlamydiae-infected
      HEC-1B cells. Preexposure of isolated, purified infectious chlamydial elementary
      bodies (EB) to C31G, at pHs 7.2 and 5.7, for 1 h at 4 degrees C resulted in
      reduced infectivity of EB for HEC-1B cells. Examination of the C31G-exposed 35S
      EB on sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographs
      and by Western blotting revealed a C31G concentration-dependent and pH-dependent
      destabilization of the chlamydial envelope, resulting in the release of
      chlamydial lipopolysaccharide and proteins. Interestingly, when the host human
      genital columnar epithelial cells were infected with chlamydiae and then exposed
      to dilute concentrations of C31G which did not alter epithelial cell viability,
      chlamydial infectivity was also markedly reduced. C31G gained access to the
      developing chlamydial inclusion causing damage to or destruction of metabolically
      active reticulate bodies as well as apparent alteration of the inclusion
      membrane, which resulted in premature escape of chlamydial antigen to the
      infected epithelial surface. These studies show that the broad-spectrum antiviral
      and antibacterial microbicide C31G also has antichlamydial activity.

PMID- 9174196
TI  - Combination therapy with amphotericin B and fluconazole against invasive
      candidiasis in neutropenic-mouse and infective-endocarditis rabbit models.
AB  - Although there are an increasing number of new antifungal agents available, the
      morbidity and mortality due to invasive mycoses remain high. The high rates of
      polyene toxicities and the development of azole resistance have raised the issue
      of using antifungal agents of these classes in combination, despite theoretical
      concerns regarding antagonism between such agents. This study was designed to
      evaluate the in vivo efficacy of combined therapy with amphotericin B and
      fluconazole against Candida albicans. Two distinct animal models were used in
      this study: a neutropenic-mouse model of hematogenously disseminated candidiasis
      and the infective-endocarditis rabbit model. Treatment efficacy was assessed by
      determining reductions in mortality as well as decreases in tissue fungal
      densities. In the neutropenic-mouse model, amphotericin B, as well as combination
      therapy, significantly prolonged survival compared to untreated controls (P < 10(
      5) and P = 0.001, respectively). The fungal densities in the kidneys of
      neutropenic mice were significantly reduced with either amphotericin B
      monotherapy or amphotericin B-fluconazole combined therapy compared to those of
      controls (P < 10(-6)). Fluconazole monotherapy also reduced fungal densities in
      the kidneys; however, this decrease was not statistically significant (P = 0.17).
      In contrast, treatment with either fluconazole alone or combined with
      amphotericin B (but not amphotericin B monotherapy) significantly decreased
      fungal densities in the brain (P = 0.025). In the rabbit endocarditis model,
      amphotericin B monotherapy or combined therapy significantly decreased fungal
      densities in cardiac vegetations (P < 0.01 versus the controls). Although no
      significant antagonism was seen when fluconazole was given in combination with
      amphotericin B, combination therapy did not augment the antifungal activity of
      amphotericin B.

PMID- 9174197
TI  - Modified agar dilution susceptibility testing method for determining in vitro
      activities of antifungal agents, including azole compounds.
AB  - In vitro activities of antifungal agents, including azole compounds, against
      yeasts were easily determined by using RPMI-1640 agar medium and by incubating
      the plates in the presence of 20% CO2. The end point of inhibition was clear by
      this method, even in the case of azole compounds, because of the almost complete
      inhibition of yeast growth at high concentrations which permitted weak growth of
      some Candida strains by traditional methods. MICs obtained by the agar dilution
      method were similar to those obtained by the broth dilution method proposed by
      the National Committee for Clinical Laboratory Standards.

PMID- 9174198
TI  - Comparison of recalcitrance to ciprofloxacin and levofloxacin exhibited by
      Pseudomonas aeruginosa bofilms displaying rapid-transport characteristics.
AB  - Attenuated total reflection Fourier transform infrared spectroscopy was used to
      measure transport of the fluoroquinolones (FQs) ciprofloxacin and levofloxacin
      into Pseudomonas aeruginosa biofilms. Biofilms were exposed to each FQ at dose
      levels of 100, 250, and 500 microg/ml for 30 min. A mathematical transport model
      was used to extract the diffusion coefficient, binding site density, and
      adsorption and desorption rates for each experiment. Recalcitrance of the
      biofilms toward each FQ was evaluated by comparison of efficacies with planktonic
      bacteria. By this criterion, biofilms were found to exhibit more recalcitrance
      toward levofloxacin than ciprofloxacin under the experimental conditions. These
      results cannot be explained by the more hindered transport of levofloxacin,
      implicating the domination of physiological factors.

PMID- 9174199
TI  - Pharmacodynamics of RP 59500 (quinupristin-dalfopristin) administered by
      intermittent versus continuous infusion against Staphylococcus aureus-infected
      fibrin-platelet clots in an in vitro infection model.
AB  - We evaluated the bactericidal activity of RP 59500 (quinupristin-dalfopristin)
      against fibrin-platelet clots (FPC) infected with two clinical isolates of
      Staphylococcus aureus, one constitutively erythromycin and methicillin resistant
      (S. aureus AW7) and one erythromycin and methicillin susceptible (S. aureus
      1199), in an in vitro pharmacodynamic infection model. RP 59500 was administered
      by continuous infusion (peak steady-state concentration of 6 microg/ml) or
      intermittent infusion (simulated regimens of 7.5 mg/kg of body weight every 6 h
      (q6h) q8h, and q12h. FPCs were infected with S. aureus to achieve an initial
      bacterial density of 10(9) CFU/g. Model experiments were run in duplicate over 72
      h. Two FPCs were removed from each model at 0, 12, 24, 36, 48, and 72 h, and the
      bacterial densities (in CFU per gram) were determined and compared to those of
      growth control experiments. Additional samples were also removed from the model
      over the 72-h period for pharmacokinetic evaluation. All regimens significantly
      (P < or = 0.01) decreased bacterial densities in the infected FPCs for both
      isolates compared to growth controls. This occurred even though MBCs were equal
      to or greater than the RP 59500 concentrations achieved in the models. There were
      no significant differences found between the dosing frequencies and levels of
      killing when examining each isolate separately. However, examination of the
      residual bacterial densities (CFU per gram at 72 h) and visual inspection of the
      overall killing effect (killing curve plots over 72 h) clearly demonstrated a
      more favorable bactericidal activity against 1199 than against the AW7 isolate.
      This was most apparent when the q8h and the q12h AW7 regimens were compared to
      all 1199 treatment regimens by measuring the 72-h bacterial densities (P < or =
      0.01). Killing (99.9%) was not achieved against the AW7 isolate. However, a 99.9%
      kill was demonstrated for all dosing regimens against the 1199 isolate. The area
      under the concentration-time curve from 0 to 24 h was found to be significantly
      correlated with reduction in bacterial density for the AW7 isolate (r = 0.74, P =
      0.04). No resistance was detected during any experiment for either isolate. RP
      59500 efficacy against constitutively erythromycin- and methicillin-resistant S.
      aureus may be improved by increasing organism exposure to RP 59500 as a function
      of dosing frequency.

PMID- 9174200
TI  - Itraconazole resistance in Aspergillus fumigatus.
AB  - Invasive aspergillosis is an increasingly frequent opportunistic infection in
      immunocompromised patients. Only two agents, amphotericin B and itraconazole, are
      licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme
      undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus
      fumigatus to itraconazole correlated with in vivo outcome has not been previously
      described. For three isolates (AF72, AF90, and AF91) of A. fumigatus from two
      patients with invasive aspergillosis itraconazole MICs were elevated. A
      neutropenic murine model was used to establish the validity of the MICs. The
      isolates were typed by random amplification of polymorphic DNA. Analysis of
      sterols, inhibition of cell-free sterol biosynthesis from [14C] mevalonate,
      quantitation of P-450 content, and [3H]itraconazole concentration in mycelial
      pellets were used to determine the mechanisms of resistance. The MICs for the
      three resistant isolates were >16 microg/ml. In vitro resistance was confirmed in
      vivo for all three isolates. Molecular typing showed the isolates from the two
      patients to be genetically distinct. Compared to the susceptible isolate from
      patient 1, AF72 had a reduced ergosterol content, greater quantities of sterol
      intermediates, a similar susceptibility to itraconazole in cell-free ergosterol
      biosynthesis, and a reduced intracellular [3H]itraconazole concentration. In
      contrast, AF91 and AF92 had slightly higher ergosterol and lower intermediate
      sterol concentrations, fivefold increased resistance in cell-free systems to the
      effect of itraconazole on sterol 14alpha demethylation, and intracellular [3H]
      itraconazole concentrations found in susceptible isolates. Resistance to
      itraconazole in A. fumigatus is detectable in vitro and is present in wild-type
      isolates, and at least two mechanisms of resistance are responsible.

PMID- 9174201
TI  - New quinoline di-Mannich base compounds with greater antimalarial activity than
      chloroquine, amodiaquine, or pyronaridine.
AB  - We have compared the ex vivo antimalarial activity of 12 new quinoline di-Mannich
      base compounds containing the 7-dichloroquinoline or 7-trifluoromethylquinoline
      nucleus with amodiaquine, chloroquine, and pyronaridine using the Saimiri
      bioassay model. Each compound was administered orally (30 mg/kg of body weight)
      to three or more noninfected Saimiri sciureus monkeys, and serum samples were
      collected at various times after drug administration and serially diluted with
      drug-free (control) serum. In vitro activity against the multidrug-resistant K1
      isolate of Plasmodium falciparum was determined in serum samples by measuring the
      maximum inhibitory dilution at which the treated monkey serum inhibited schizont
      maturation in vitro. Of the 12 Mannich bases tested, 8 were associated with
      levels of ex vivo antimalarial activity in serum greater than those of
      amodiaquine, chloroquine, or pyronaridine 1 to 7 days after drug administration.
      Further studies were carried out with four of these compounds, and the results
      showed that the areas under the serum drug concentration-time curves for the four
      compounds were between 7- and 26-fold greater than that obtained for
      pyronaridine. Activity against four multidrug-resistant strains of P. falciparum
      was also much greater in serum samples collected from monkeys after
      administration of these four compounds than in serum samples collected after
      administration of pyronaridine or chloroquine. These findings suggest that these
      four quinoline Mannich base compounds possess a very marked and prolonged
      antimalarial activity and that further studies should be performed to determine
      their value as antimalarial drugs.

PMID- 9174202
TI  - Candida norvegensis: a fluconazole-resistant species.
AB  - Candida norvegensis has been an unusual cause of infections in humans. In Norway
      this species was isolated from eight patients from 1990 to 1996 and was of
      probable pathogenic significance in four of them. All isolates were resistant to
      fluconazole. The same was true for two C. norvegensis isolates from before 1940,
      and it is therefore assumed that the fluconazole resistance is inherent.

PMID- 9174203
TI  - Pharmacodynamic properties of BAY 12-8039 on gram-positive and gram-negative
      organisms as demonstrated by studies of time-kill kinetics and postantibiotic
      effect.
AB  - Time-kill kinetics of BAY 12-8039 were studied at two inocula against three
      strains each of Bacteroides fragilis, Escherichia coli, Staphylococcus aureus,
      Haemophilus influenzae, and Streptococcus pyogenes. The postantibiotic effects of
      BAY 12-8039 were studied on three strains each of E. coli, S. aureus, H.
      influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae. The
      pharmacodynamic data demonstrated that BAY 12-8039 has marked activity against
      gram-positive and gram-negative organisms (under both anaerobic and aerobic
      conditions) and anaerobes. BAY 12-8039 also exhibited a postantibiotic effect of
      >1 h for all strains except one E. coli strain.

PMID- 9174204
TI  - Pseudomonas aeruginosa isolates from patients with cystic fibrosis have different
      beta-lactamase expression phenotypes but are homogeneous in the ampC-ampR genetic
      region.
AB  - Pseudomonas aeruginosa isolates from 1 of 17 cystic fibrosis patients produced
      secondary beta-lactamase in addition to the ampC beta-lactamase. Isolates were
      grouped into three beta-lactamase expression phenotypes: (i) beta-lactam
      sensitive, low basal levels and inducible beta-lactamase production; (ii) beta
      lactam resistant, moderate basal levels and hyperinducible beta-lactamase
      production; (iii) beta-lactam resistant, high basal levels and constitutive beta
      lactamase production. Apart from a base substitution in the ampR-ampC intergenic
      region of an isolate with moderate-basal-level and hyperinducible beta-lactamase
      production, sensitive and resistant strains were identical in their ampC-ampR
      genetic regions. Thus, enhanced beta-lactamase expression is due to mutations in
      regulatory proteins other than AmpR.

PMID- 9174205
TI  - Isolation of a gene encoding a novel spectinomycin phosphotransferase from
      Legionella pneumophila.
AB  - A gene capable of conferring spectinomycin resistance was isolated from
      Legionella pneumophila, the agent of Legionnaires' disease. The gene (aph)
      encoded a 36-kDa protein which has similarity to aminoglycoside
      phosphotransferases. Biochemical analysis confirmed that aph encodes a
      phosphotransferase which modifies spectinomycin but not hygromycin, kanamycin, or
      streptomycin. The strain that was the source of aph demonstrated resistance to
      spectinomycin, and Southern hybridizations determined that aph also exists in
      other legionellae.

PMID- 9174206
TI  - Pharmacodynamic effects of amoxicillin versus cefotaxime against penicillin
      susceptible and penicillin-resistant pneumococcal strains: a phase I study.
AB  - Serum bactericidal activity against a penicillin-susceptible strain and a
      penicillin-resistant strain of Streptococcus pneumoniae (amoxicillin and
      cefotaxime MICs, 0.001 and 1 microg/ml, respectively, and MBCs, 0.01 and 2
      microg/ml, respectively) was measured in 12 healthy volunteers who each received
      an oral 875-mg dose of amoxicillin and an intramuscular 1-g dose of cefotaxime in
      a crossover fashion. The areas under the bactericidal activity-time curves for
      the two strains were found to be similar for both antibiotics despite the
      significantly higher (P < 0.002) AUC/MIC and peak level/MIC values for
      cefotaxime.

PMID- 9174207
TI  - Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B
      tested against Candida albicans.
AB  - Time-kill curves were determined for three isolates of Candida albicans tested
      against fluconazole and amphotericin B at multiples of the MIC. Fluconazole
      produced fungistatic activity, with concentration-related growth effects observed
      over a narrow range of concentrations. Amphotericin B exhibited fungicidal
      activity, with enhancement of activity over a broader range of concentrations.

PMID- 9174208
TI  - Apparent involvement of a multidrug transporter in the fluoroquinolone resistance
      of Streptococcus pneumoniae.
AB  - A Streptococcus pneumoniae strain selected for resistance to ethidium bromide
      demonstrated enhanced energy-dependent efflux of this toxic dye. Both the
      ethidium resistance and the ethidium efflux could be inhibited by the plant
      alkaloid reserpine. The ethidium-selected cells demonstrated cross-resistance to
      the fluoroquinolones norfloxacin and ciprofloxacin; this resistance could also be
      completely reversed by reserpine. Furthermore, reserpine potentiated the
      susceptibility of wild-type S. pneumoniae to fluoroquinolones and ethidium. The
      most plausible explanation for these results is that S. pneumoniae, like some
      other gram-positive bacteria, expresses a reserpine-sensitive multidrug
      transporter, which may play an important role in both intrinsic and acquired
      resistances of this pathogen to fluoroquinolone therapy.

PMID- 9174209
TI  - Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in
      healthy adult volunteers.
AB  - The steady-state concentrations of clarithromycin and azithromycin in plasma were
      compared with concomitant concentrations in epithelial lining fluid (ELF) and
      alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy
      and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean
      plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin
      concentrations were similar to those previously reported. Clarithromycin was
      extensively concentrated in ELF (range of mean +/- standard deviation
      concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h)
      and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The
      concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22
      +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h
      to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)
      hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to
      31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug
      administration, azithromycin and clarithromycin achieved mean concentrations in
      ELF and AM higher than the concomitant concentrations in plasma.

PMID- 9174210
TI  - In vitro assessment of the effect of clavulanic acid at concentrations achieved
      in human serum on the bactericidal activity of amoxicillin at physiological
      concentrations against Staphylococcus aureus: implications for dosage regimens.
AB  - The effects on Staphylococcus aureus viability and beta-lactamase activity of
      concentrations that simulated those in human serum after a combined dose of 875
      mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro
      pharmacodynamic model. Six hours of preexposure to concentrations of the
      amoxicillin-clavulanic acid combination that were higher than the amoxicillin
      clavulanic acid MIC led to a reduction of the initial inoculum of >90% and to a
      significant decrease of beta-lactamase activity versus those of the control even
      from 6 h, when concentrations were subinhibitory. The postantibiotic effect and
      post-beta-lactamase inhibitor effect contributed to these results.

PMID- 9174211
TI  - In vitro susceptibilities of clinical isolates of vancomycin-resistant
      enterococci.

PMID- 9174212
TI  - Time-kill curves for a semisynthetic glycopeptide, LY333328, against vancomycin
      susceptible and vancomycin-resistant Enterococcus faecium strains.

PMID- 9174213
TI  - Vancomycin dependence in a vanA-producing Enterococcus avium strain with a
      nonsense mutation in the natural D-Ala-D-Ala ligase gene.

PMID- 9174214
TI  - The effect of vancomycin on the structure of vancomycin-susceptible and 
      resistant Enterococcus faecium strains.

PMID- 9174215
TI  - High frequency oscillation and exogenous surfactant in the treatment of neonatal
      respiratory distress syndrome.
AB  - Surfactant therapy has become widely used in neonates suffering from respiratory
      distress syndrome. High frequency oscillation has been shown to be efficient and
      safe in animal models, but somewhat less convincing in human neonates. An
      overview is given of the experimental and clinical data assessing the combination
      of these two techniques. Personal preliminary data are briefly presented.

PMID- 9174216
TI  - Longitudinal monitoring of bone mineral density in thalassemic patients. Genetic
      structure and osteoporosis.
AB  - The changes in bone mineral density (BMD) measured by single photon
      absorptiometry (SPA) using two observations conducted over a period of 2 years
      were examined in 54 thalassemic subjects [30 F(A) and 24 M(B)] with a
      chronological age ranging from 2.6 to 22.6 years and in 27 sex- and age-matched
      controls (C). Each category (A, B and C) was divided into three groups according
      to pubertal signs: pre-pubertal subjects (A1, B1 and C1); peri-pubertal subjects
      (A2, B2 and C2) and pubertal subjects from the first observation (A3, B3 and C3).
      Furthermore, each group of patients was divided into sub-groups on the basis of
      haematological phenotypes, those with a more severe form were called beta0/beta0
      while those with other forms were called "others". The most significant findings
      were the following: the presence of a more severe reduction of the bone mineral
      density in patients with the beta0/beta0 phenotype than in patients with the
      "others" phenotype; patients with hypogonadism corresponded to the beta0/beta0
      phenotype, while those with spontaneous puberty corresponded to the "others"
      phenotype. In conclusion, since puberty and the degree of bone mineral density
      are related to the haematological phenotype, puberty (spontaneous or induced)
      positively influences the bone mineral density only at the start of puberty,
      while subsequently, the degree of osteoporosis is the expression of widespread
      and chronic systemic damage due to the haematological phenotype.

PMID- 9174217
TI  - Carbohydrate intolerance after acute gastroenteritis--a disappearing problem in
      Polish children.
AB  - The prevalence of carbohydrate intolerance in Polish children during an acute
      episode of gastroenteritis was determined. One hundred and seven consecutive
      children, less than 3 years old, with acute diarrhoea were enrolled into the
      study. Carbohydrate intolerance (diagnostic criteria: >0.5% reducing substances
      and stool pH less than 5.5) was diagnosed in 14/107 (13.08%) children: lactose
      intolerance was present in 12 (11.2%) patients; glucose polymer intolerance in 1
      (0.93%) and monosaccharide intolerance in 1 (0.93%). The most important
      predisposing factor was rotavirus. In all cases the carbohydrate intolerance was
      transient, resolving within 5 days. Carbohydrate intolerance is also an
      infrequent problem in Polish children. Restriction of lactose-containing foods
      (use of lactose-free or low lactose formulas) for the majority of children with
      gastroenteritis does not seem to be justified.

PMID- 9174218
TI  - Wheezing bronchitis reinvestigated at the age of 10 years.
AB  - We have reinvestigated 92/101 children aged 10, who before the age of 2 years
      were admitted to a paediatric ward due to wheezing bronchitis. At the present
      time, 70% are symptom-free without medication, 20% have mild asthma, 8% moderate
      and 2% severe asthma. Persistent asthma correlated significantly to the presence
      of some other atopic disease in recent years, to early start of wheezing during
      infancy and to intense obstructive disease as a young child, while initial
      respiratory syncytial virus infection did not. A clear-cut relationship between
      smoking in the home in infancy and persistent asthma emerged (not visible at a
      preschool follow-up). The histamine challenge results correlated to the clinical
      picture. A normal histamine challenge was seen in 63%, mild hyperresponsiveness
      in 19%, moderate in 12% and pronounced hyperresponsiveness in 6%. The figures for
      persistent asthma and bronchial hyperresponsiveness are high compared with the
      prevalence of asthma in the overall population of schoolchildren.

PMID- 9174219
TI  - Helicobacter pylori duodenal colonization in children.
AB  - To investigate the prevalence and the significance of Helicobacter pylori
      duodenal colonization, endoscopic duodenal biopsies were performed in 168
      children with chronic abdominal pain, gastroesophageal reflux, gastrointestinal
      bleeding, and malabsorption syndrome. Helicobacter pylori infection was detected
      in 68 children (40.4%): in 31 of them H. pylori was present in the gastric
      antrum, and in 37 in the duodenum also. Duodenitis was observed in 25 children
      with duodenal H. pylori; gastric metaplasia in 3. Scanning electron microscopy
      revealed the presence of the micro-organism in 3/13 cases; the bacteria were
      located in the intercellular spaces and alterations of the epithelial surface
      were found. In conclusion, H. pylori gastritis in children is often associated
      with duodenal colonization which can cause duodenitis, and also without gastric
      metaplasia, which indicates a possible role of the micro-organism in the
      pathogenesis of the lesions.

PMID- 9174220
TI  - Nerve conduction and autonomic nerve function in diabetic children. A 10-year
      follow-up study.
AB  - In order to study the long-term development of diabetic neuropathy in children
      with newly diagnosed diabetes mellitus, 144 children were entered in a
      prospective study of nerve conduction and autonomic nervous function.
      Neurophysiological recordings of nerve conduction and parasympathetic function (R
      R variations) were made at onset of diabetes and after 2, 5 and 10 years. Low
      sensory nerve conduction and autonomic dysfunction were found in approximately
      25% of the children at onset of diabetes when the patients were not yet in
      complete remission. During years 0-2, an initial improvement of sensory
      conduction velocities was found. After 2 years, deteriorations in sensory and
      motor nerve conduction and autonomic nerve function were common and further
      deterioration was seen over time. A correlation was found between nerve
      conduction and glycaemic control.

PMID- 9174221
TI  - Dilation mechanism, causes of restenosis and stenting in balloon coarctation
      angioplasty.
AB  - This review focuses on the individual dilation mechanism, the possible cause of
      restenosis after balloon angioplasty and the clinical application of a stent in
      coarctation of the aorta. Balloon angioplasty is still not the first choice of
      therapy in neonates with native coarctation because of the potential risk of
      aortic disruption, the high incidence of restenosis and the satisfactory results
      of surgical coarctectomy. Intravascular ultrasound imaging provides the
      individual mechanism of aortic dilation by balloon, and this will be a new
      modality for assessing the relationship between restenosis and aortic luminal
      morphology after balloon dilation. Although the cause of restenosis after balloon
      angioplasty remains uncertain, it may be due to a combination of elastic recoil
      by ductal tissue constriction, intimal hyperplasia and arterial remodelling. A
      stent could be an effective alternative to conventional balloon angioplasty in
      native coarctation of the aorta, preventing ductal tissue constriction. However,
      the problematic relationship between patient growth and relative stenosis of the
      stent should be clarified before clinical application of a stent for this
      disease.

PMID- 9174222
TI  - Motor impairments in children with epilepsy treated with carbamazepine.
AB  - Nineteen children with epilepsy were tested on two occasions, first during
      treatment with carbamazepine (CBZ) and then 6 months later without treatment.
      Plasma drug concentrations were within the therapeutic limits in all children.
      The children were examined with a standardized test of gross- and fine- motor
      functions, the Bruininks-Oseretsky test of motor proficiency. Significant
      improvements were found in response speed (p < 0.05), in composite fine-motor
      tests (p < 0.01) and in the total test battery (p < 0.05) after the treatment had
      been withdrawn. A tendency to improvement was found in the fine-motor subtest of
      upper limb coordination (p = 0.08). Another group of 12 children was tested twice
      during treatment with CBZ with an interval of 6 months. No difference was found
      in this group except for an impairment of the results in the subtest of visual
      motor control on the second test occasion (p = 0.05).

PMID- 9174223
TI  - Serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal
      propeptide of type III procollagen and laminin P1 in Duchenne muscular dystrophy.
AB  - The striking proliferation of connective tissue in Duchenne muscular dystrophy is
      attributed, besides other components of the extracellular matrix, to an increase
      of endomysial and perimysial type III and type I collagen. We investigated if
      muscle fibrosis correlates to an increased serum concentration of procollagen I
      or III. Therefore, we measured the serum levels of carboxyterminal propeptide of
      type I procollagen, aminoterminal propeptide of type III procollagen and laminin
      P1 in 20 boys with progressive muscular dystrophy (16 definite Duchenne muscular
      dystrophy, 2 suspected of Duchenne muscular dystrophy, 2 Becker muscular
      dystrophy). In contrast to collagen I and III the expression of laminin in the
      basement membrane is known to be normal in Duchenne muscular dystrophy. There was
      no significant alteration of serum concentration of procollagen III N-peptide,
      procollagen I C-peptide and laminin P1 in boys with Duchenne muscular dystrophy.
      Measuring these parameters is not useful for investigating the extent of muscle
      fibrosis or for monitoring the effect of therapeutic trials such as steroid
      treatment.

PMID- 9174224
TI  - Elevated sleep arousal thresholds in enuretic boys: clinical implications.
AB  - Enuretic children are described as difficult to arouse from sleep. We studied
      auditory sleep arousal thresholds in enuretic boys and report on the clinical
      implications of these findings. Fifteen enuretic and 18 control subjects (7-12
      year-old males) were studied in a sleep laboratory for four consecutive nights
      using standard polysomnographic recording techniques. Sleep was undisturbed for
      the initial two nights and waking thresholds were measured on the following two
      nights. Enuretic children wet most frequently in the first two-thirds of the
      night. Arousal attempts were successful 39.7% of the time in controls and only
      9.3% of the time in enuretics. In conclusion, enuretic males were more difficult
      to arouse than age-matched controls. The elevated arousal thresholds may be due
      to delayed maturation. Treatment programmes that rely on awakening should be
      aware of these features.

PMID- 9174225
TI  - Diurnal plasma vasopressin and urinary output in adolescents with monosymptomatic
      nocturnal enuresis.
AB  - Plasma arginine vasopressin (AVP) levels, urinary flow and urine osmolality were
      investigated in a group of adolescents (20 boys and 5 girls), aged 11-21 y, with
      severe monosymptomatic nocturnal enuresis and a control group of healthy
      adolescents (16M and 4F) with similar age- and sex-distribution. Half of the
      control group was investigated twice, with an interval of 6 months. AVP samples
      were taken every fourth hour in all adolescents and half of the control group
      were also investigated every second hour to achieve more samples during
      controlled sleep. After the study the enuretic group were put on long-term oral
      desmopressin (DDAVP). The difference between day and night values of AVP was
      significant for both groups, but there was no difference in the day/night ratios
      of plasma-AVP. All the adolescents produced less urine while asleep, but the
      controls produced significantly more urine than the enuretics during day. The
      controls also had a significantly larger nocturnal elevation of urine osmolality
      than the enuretics, thus a tendency towards polyuria was found. We could not find
      any significant difference between responders to DDAVP treatment and non
      responders in any of the parameters studied. AVP is secreted in a pulsatile
      fashion and with point hormone samples taken every fourth or second hour we were
      unable to find any difference in the diurnal AVP secretion between enuretics and
      normal controls.

PMID- 9174226
TI  - Use of new Nordic criteria for classification of SIDS to re-evaluate diagnoses of
      sudden unexpected infant death in the Nordic countries.
AB  - To investigate whether changes in diagnostic practice might be the cause of the
      SIDS epidemic in the Nordic countries in the 1970s and 1980s a cooperative study
      was initiated in 1990. Common morphologic diagnostic criteria for SIDS were
      established in 1992 and 127 randomly selected sudden unexpected infant deaths
      from all Nordic countries from 1970 to 1995 and 205 cases from the Institute of
      Forensic Medicine, Oslo, Norway (RMI) from 1984 to 1995 were re-evaluated blindly
      using the new criteria. Neither the increase nor the decline in the SIDS rate
      since 1989 seemed to be due to changed diagnostic practices. SIDS seemed to have
      been under-diagnosed before the new criteria came into operation in 1992. There
      were fewer discrepancies between the original and revised diagnoses in the RMI
      cases than in the rest of the Norwegian cases, both before and after 1992.

PMID- 9174227
TI  - Follow-up results of different treatment programs for obese children.
AB  - OBJECTIVE: Many approaches have been tried in order to tackle the problem of
      obesity in children, but most of them have failed to achieve long-term weight
      loss. Cognitive behaviour therapy tends to predict good prospects. So far, no
      studies have investigated the surplus value of introducing a "healthy-eating"
      lifestyle program instead of a strict diet prescription, in combination with the
      principles of cognitive behaviour therapy. Therefore, a new program was designed.
      The second aim of the study was to evaluate the impact of different forms of
      therapeutic contact. SUBJECTS AND METHODS: The obese group consisted of 205
      children seeking treatment, and a control group of 54 obese school children. The
      effects of the program were evaluated by means of a pre-test/post-test design
      with a 1-y follow-up. Subjects were assigned to different therapeutic conditions:
      group therapy, individual therapy, summer camp or "advice in one session".
      RESULTS: A progressive and significant loss of weight for all therapeutic
      conditions was noticeable. The reduction continued at least 6 months after
      completing therapy. The control group, however, showed weight evolution in the
      opposite sense. CONCLUSIONS: A replication of the positive effect of CBT was
      found in a broad sample of clinically obese children, even without strict diet
      prescription. Our hypothesis that group approach will result in a better outcome
      is borne out.

PMID- 9174228
TI  - Thermal balance in term and preterm newborn infants nursed in an incubator
      equipped with a radiant heat source.
AB  - A radiant hood warmer, a device that heats the incubator roof independently of
      the incubator's main heat source, was used to study the thermal balance of 11
      full term and 13 preterm (gestational age 25-34 weeks) infants exposed to an
      isolated elevation of incubator roof temperature at stable ambient air
      temperature and humidity. After initial measurements without active heating of
      the incubator roof, the hood warmer was set to 33 degrees C, 36 degrees C and
      finally (preterm infants only) to 39 degrees C. At least 18 min of measurements
      with the infant asleep were made at each hood warmer setting. In the term infants
      an increase in roof temperature from 30.5 degrees C to 35.6 degrees C resulted in
      an increase in skin temperature from 35.4 to 35.9 degrees C, and a decrease in
      radiative heat loss from 32.8 to 20.7 W/m2 exposed skin. In the preterm infants
      an increase in roof temperature from 31.0 to 38.4 degrees C led to an increase in
      skin temperature from 35.7 to 36.3 degrees C and a decrease in radiative heat
      loss from 34.1 to 13.0 W/m2 exposed skin. The increased inner roof surface
      temperature did not affect evaporative or convective heat loss, skin blood flow,
      respiratory water loss, oxygen consumption or transepidermal water loss in either
      group. Thus, at stable ambient air temperature and humidity, the increase in
      incubator roof temperature resulted in an increase in skin temperature and a
      decrease in radiative heat loss in both term and preterm infants.

PMID- 9174229
TI  - Effect of lipid emulsion on IL-2 production by mononuclear cells of newborn
      infants and adults.
AB  - The in vitro effect of a lipid emulsion (intralipid) on interleukin-2 (IL-2)
      production by cord blood mononuclear cells (CBMC) of preterm and term newborn
      infants was examined and compared to that of peripheral blood mononuclear cells
      (PBMC) of adults. Intralipid, added at concentrations accepted in clinical
      practice, caused a dose-dependent inhibition of IL-2 activity tested by bioassay.
      IL-2 levels, tested by radioimmunoassay (RIA), were found to be reduced only in
      supernatants derived from CBMC of term infants and not in those derived from MC
      of preterm infants or adults. The capacity of the IL-2 dependent cell line CTLL-2
      to respond to IL-2 was abolished in the presence of intralipid, suggesting an
      interference with the binding of IL-2 to its receptor on these cells. It is
      conceivable that administration of intralipid to preterm infants may interfere
      with the binding of IL-2 to the specific receptors on their activated
      lymphocytes, with a possible subsequent suppression of their immune response.

PMID- 9174230
TI  - Low density lipoprotein in neonates with high cord serum cholesterol levels.
AB  - Differences in cord serum low density lipoprotein (LDL) composition between male
      and female neonates with normal or high (> or = 100 mg/dl or > or = 2.59 mmol/l)
      serum cholesterol levels were studied in 548 full-term newborn infants of the
      Toledo Study (Spain), where the absence of known perinatal factors that would
      alter lipid levels in cord blood was confirmed. The percentage of females with a
      high serum total cholesterol (TC) level was higher (p < 0.02) than that of males.
      ANOVA two-way analysis shows significant interaction of gender and cholesterol
      level upon LDL-cholesterol, triglycerides and LDL-cholesterol/Apoprotein (Apo) B
      ratio. However, Apo B was higher in those neonates, both male and female, with
      high cholesterol levels. The LDL fraction carried about 55% of TC in females with
      high TC levels (HF), whereas it transported just 40% in males with high TC levels
      (HM). LDL appeared more enriched in cholesterol than in Apo B in HF than in HM (p
      < 0.01). An increased level of small LDL particles should be associated with the
      higher triglyceride level found amongst HM. Results in LDL composition suggest
      that metabolic gender-related differences in infants with normal or high TC are
      presented at birth.

PMID- 9174231
TI  - Effects of bottle feeding and two different methods of gavage feeding on
      oxygenation and breathing patterns in preterm infants.
AB  - OBJECTIVE: To determine the effect of bottle feeding, as compared to two methods
      of gavage feeding, on apnoea, bradycardia and oxygen desaturation frequency.
      PATIENTS: Thirty preterm infants breathing room air; gestational age 28.6 +/- 2.1
      weeks at birth and 34 +/- 1.4 weeks at study (mean +/- SD). METHODS: Nine-hour
      recordings of pulse oximeter saturation (SpO2), pulse waveforms,
      electrocardiogram, breathing movements and nasal airflow. Administration of 21 +/
      1.5 ml/kg of milk/feed in 3-h intervals using three different feeding techniques
      in random order: bottle feeding, bolus gavage feeding, and slow gavage feeding (1
      h). Analysis of recordings for apnoeas (> or =4s, bradycardias (heart rate < 2/3
      of baseline), and episodic desaturation (SpO2 < or = 80%). RESULTS: There were
      three times more desaturations with bottle feeding than with bolus gavage feeding
      (p < 0.001), but no further reduction with slow gavage feeding. With all three
      feeding techniques, there were significantly more desaturations in the hour when
      the feeds were given than during the following 2 h. The deleterious effects of
      bottle feeding were most evident during the hour of feeding, but desaturation
      frequency remained significantly higher than with gavage feeding during the
      following 2 h. There was no significant effect of feeding technique on the
      frequency of apnoea or bradycardia. CONCLUSIONS: Preterm infants who are normally
      oxygenated in room air may have significant desaturation during bottle feeding.
      Such desaturation can be effectively reduced by gavage feeding. Slow gavage
      feeding offers no advantage over bolus gavage feeding with respect to the
      avoidance of hypoxaemia.

PMID- 9174232
TI  - Genotypic/phenotypic heterogeneity of selective vitamin B12 malabsorption
      (Grasbeck-Imerslund syndrome) in two Bedouin families.
AB  - We report on seven patients in two unrelated consanguineous Bedouin families with
      Grasbeck-Imerslund syndrome. Pedigree analysis in Family 1 was suggestive of an X
      linked mode of inheritance. Intra- and inter-familial heterogeneity was elicited
      among the affected children in both families. Two of the affected sibs in each
      family had raised Hb A2 (>4%) while a third in Family 1 had a raised level of Hb
      F before treatment. One of the patients developed subacute combined degeneration
      of the cord at the age of 17 years before the correct diagnosis was made. All
      abnormalities were corrected following the institution of parenteral cobalamin
      therapy.

PMID- 9174233
TI  - Reactivity of skin blood flow and heart rate to external thermal stimulation in
      anencephaly.
AB  - Oscillations of skin blood flow and heart rate can be synchronised using external
      rhythmic thermal stimulation in healthy adults and infants. We examined the
      effect of thermal stimulation on the cutaneous circulation and heart rate of an
      anencephalic neonate using cutaneous laser Doppler flowmetry and ECG monitoring.
      The results suggest that synchronisation of SBF and HR to thermal stimulation can
      also be induced in an anencephalic newborn.

PMID- 9174234
TI  - Neonatal respiratory distress in near-term infants--consider surfactant protein B
      deficiency.
AB  - Two infants presenting with respiratory distress in the first 24 h of life are
      described. Both patients underwent extensive investigation before the diagnosis
      of surfactant protein B-deficiency was reached. Both children died within 2
      months of birth. Parental consanguinity was known to be a feature in the first
      case, who proved to have a previously unrecognized mutation of the surfactant
      protein B gene. In the second case, a history of parental consanguinity was not
      sought from the Caucasian family, but was later volunteered by the parents
      themselves. Case 2 proved to have the "common" surfactant protein B-deficient
      genotype. The key to diagnosis is having a high index of suspicion in any term or
      near-term newborn with severe respiratory distress; parental consanguinity must
      be excluded. Surfactant protein B-deficiency can be readily diagnosed from
      bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well
      tolerated in newborns.

PMID- 9174235
TI  - Late-appearing diaphragmatic hernia following resolution of right pleural
      effusion.
AB  - A case of late-appearing congenital diaphragmatic hernia in a premature infant
      with previously normal chest X-ray is reported. Pleural effusion accumulation and
      resolution preceded herniation of the liver to the right hemithorax and
      development of respiratory symptoms. Chest X-ray, ultrasound and computed
      tomography of the chest were useful in establishing the correct diagnosis.
      Pleural effusion without obvious cause should alert the paediatrician to the
      possibility of this rare condition.

PMID- 9174236
TI  - Intrathecal methotrexate overdose.
AB  - We report two cases of intrathecal methotrexate overdose. A 3-y-old girl with
      acute lymphoblastic leukaemia and a 4-y-old boy with Burkitt's lymphoma were to
      receive an intrathecal injection of methotrexate after completion of intravenous
      methotrexate infusion. Instead of 12.5 mg, they both received a dose of 125 mg.
      Both children developed generalized convulsion 3 h after the overdose, but
      afterwards recovered completely. Intravenous folinic acid and dexamethasone
      rescue were employed, but no attempt was made to exchange the cerebrospinal
      fluid. In addition to the staff's failure to check the drug label carefully, the
      marked resemblance of the two dose preparations of methotrexate (50 mg/5 ml and
      500 mg/5 ml) may have been contributory.

PMID- 9174237
TI  - Anti-neutrophil autoantibodies and systemic vasculitis: a report of five cases.

PMID- 9174238
TI  - Lactobacillus GG supplementation does not reduce faecal colonization of
      Klebsiella oxytoca in preterm infants.

PMID- 9174239
TI  - Lithium-pilocarpine status epilepticus in the immature rabbit.
AB  - Although status epilepticus in children is associated with neuronal pathologies,
      there are few developmental models of status epilepticus which produce damage in
      the immature brain. We have developed a new model of status epilepticus using
      systemically injected pilocarpine in immature rabbits pretreated with lithium.
      Injected animals demonstrated behavioral and electrographic seizures. Behavioral
      seizures were characterized by sustained or recurrent bouts of clonus in all
      limbs. The pilocarpine-induced seizures had a 40% mortality. All animals
      surviving the status epilepticus had hippocampal lesions when evaluated 48 h
      after the SE. Within the hippocampus, CA1 pyramidal cells were the most
      vulnerable cell population. Extrahippocampal damage was seen in the majority of
      animals. Our results show that severe seizures cause hippocampal lesions in the
      absence of hypoxemia and suggest that the presumed resistance of the immature
      brain to seizure-induced damage is not a general rule which can be applied to all
      models or species.

PMID- 9174240
TI  - A target of the HoxB5 gene from the mouse nervous system.
AB  - An epitope-specific antibody against the protein product of the murine HoxB5 gene
      was used to select an enriched library of Hox target sequences. Genomic DNA was
      purified by immunoaffinity chromatography, using glutaraldehyde-cross-linked
      chromatin from CNS of mouse embryos at gestational day 15. Screening was done by
      colony hybridization with TAAT-containing oligonucleotides, filter DNA-protein
      binding, and gel mobility shift assay. Nucleotide sequencing identified a 910 bp
      DNA fragment, containing a consensus Antennapedia-like binding site, and
      identical in 640 bps at 3' end of the clone to the promoter of the SPI3 gene,
      which encodes a serine protease inhibitor protein [Sun, J., Rose, J.B. and Bird,
      P., J. Biol. Chem., 270 (1995) 16089-16096]. In situ hybridization experiments
      were performed to see if a correlation could be found between the expression
      patterns the SPI3 and the HoxB5 genes. Using a 120 bp cDNA fragment as probe,
      SPI3 expression was detected mainly in the CNS of 15 day mouse embryos, a pattern
      which is similar to that of the HoxB5 gene at this stage [Hogan, B.L., Holland,
      P.W. and Lumsden, A., Cell Diff. Dev., 25 Suppl. (1988) 39-44; Sakach, M. and
      Safaei, R., Int. J. Dev. Neurosci., 14 (1996) 567-573]. In conclusion, data
      presented here suggest that the SPI3 gene is a candidate target of the HoxB5 gene
      in vertebrate embryos.

PMID- 9174241
TI  - Calcium-sensing receptor in the rat hippocampus: a developmental study.
AB  - The extracellular Ca2+ (Ca2+(o))-sensing receptor (CaR) plays a key role in
      maintaining near constancy of Ca2+(o) in mammals through its presence in
      parathyroid gland and kidney. The CaR is also present in brain, and although its
      role(s) in the brain is not known, it is possible that small changes in Ca2+(o)
      modify essential physiological and pathological processes, since calcium is
      crucial for numerous neuronal functions. Northern analysis has revealed that the
      CaR mRNA is present in hippocampus and several other regions of the brain. The
      hippocampus is an important site for learning and memory, but the relevance of
      the CaR to these processes is unknown. Long-term potentiation (LTP), a putative
      in vitro analog of memory, can only be induced after 7-10 days postnatally in rat
      hippocampus. Therefore, in the present study we determined the time course for
      the developmental expression of the CaR in rat hippocampus to assess its
      relationship to the development of other important hippocampal functions, such as
      the capacity for induction of LTP. Northern and Western analyses showed that CaR
      mRNA and protein were expressed at low levels at 5 days postnatally but then
      increased markedly at 10 days. A high level of receptor expression, due primarily
      to an increase in a 7.5 kb transcript, persisted until 30 days, when it gradually
      decreased by 3-fold to reach the adult level of expression. In situ hybridization
      histochemistry and immunohistochemistry revealed CaR mRNA and protein in
      pyramidal cells of all the layers of hippocampus and in granule cells of the
      dentate gyrus. The results show that CaR expression rises at a time when LTP can
      first be induced in hippocampus and persists at high levels during the time when
      brain development is proceeding most rapidly. Further studies are needed to
      determine the role of the CaR in the development of important aspects of the
      function of hippocampus and other regions of brain, including LTP.

PMID- 9174242
TI  - Neurobehavioral evaluation of lurcher mutant mice during ontogeny.
AB  - Lurcher mutant mice were compared to normal littermate controls for body weight,
      body righting, negative geotropism, sensorimotor coordination (rotating grid,
      wire suspension, rotorod), and visuomotor coordination requiring swimming toward
      a pole during postnatal (P) days 0-30. Lurcher mutants had a lower body weight on
      P20-P30 and were slower before performing the complete body righting response on
      P13-P30. Because of postural instability during the negative geotropism test,
      lurcher mutants turned quicker up the slope than normal mice. The mutants fell
      sooner from the rotating grid on P11-P14, from the horizontal wire on P15-P16,
      and from the rotorod on P14-P30. Lurcher mutants were also slower before swimming
      to the pole or climbing to the top of the pole and were inferior in pole climbing
      height on P22-P30. These results indicate test-selective and time-selective
      neurobehavioral deficits during ontogeny in a spontaneous cerebellar mutant.

PMID- 9174243
TI  - Dextromethorphan ameliorates effects of neonatal hypoxia on brain morphology and
      seizure threshold in rats.
AB  - Hypoxic injury to the brain is mediated in part by NMDA receptors. Therefore,
      NMDA receptor blockade with dextromethorphan (DM), a non-competitive channel
      blocker, was hypothesized to ameliorate injury even when given after the hypoxic
      insult. Rats were exposed to 8% oxygen for 3 h on postnatal day 7. Within 20 min
      of exposure, animals received 30 mg/kg i.p. DM or normal saline. Littermates
      maintained in room air for 3 h also received DM or saline. At 14 days of age, 7
      days after exposure, cortical thickness and hippocampal area were measured. At 70
      90 days of age, approximately two months after exposure, in a separate group of
      rats, seizure threshold using pentylenetetrazol (PTZ) and passive avoidance
      learning and retention were determined. There were no gross changes in cellular
      morphology and no evidence for cellular necrosis in any of the exposure groups.
      However, cortical thickness was decreased in animals exposed to hypoxia. DM
      administration prevented this decrease. Hippocampal area was unaffected. Seizure
      susceptibility in adulthood was increased in animals exposed to hypoxia in the
      neonatal period. DM prevented the decrease in seizure threshold. There was no
      difference in passive avoidance learning or retention as a function of neonatal
      exposure condition. Mild to moderate hypoxia, previously thought not to produce
      any histologic changes, causes significant short-term loss of cortical thickness
      and long-term decrease in seizure threshold. DM appears to ameliorate these
      effects even when given after the hypoxic insult. These results implicate the
      glutamate receptor system in the pathophysiology of hypoxia damage and suggest
      that treatment with a glutamate receptor blocker when neonatal asphyxia is
      suspected would help ameliorate the consequences of such an insult.

PMID- 9174244
TI  - Decreased receptivity of pathway connective tissue to sympathetic nerve ingrowth
      in the developing rat.
AB  - Sympathetic axons can form atypical pathways to denervated orbital targets in
      neonatal rats but not in rats aged 30 or more days. The objective of this study
      was to determine if connective tissue pathways that carry sympathetic nerves lose
      their ability to sustain axonal sprouting during the early postnatal period.
      Regions of periorbital sheath known to contain large numbers of sympathetic axons
      that travel to distal orbital targets were excised from rats (sympathectomized 3
      days previously) on postnatal days 6-7, 14-15, 30-31, and 48-49 and placed in
      anterior chambers of adult host rats. Tissues were removed 3, 6, or 10 days post
      transplant and sympathetic ingrowth was analyzed by catecholamine
      histofluorescence in whole-mount or cryosectioned specimens. Connective tissue
      transplants from 6-15-day-old donors showed significant fiber ingrowth by 3 days
      in oculo, and innervation was maximal by 6 days. In contrast, sprouting into 30
      49-day-old tissue was significantly slower, with most transplants lacking fibers
      at 3 days, and with small numbers of short fibers present at 6 days. We conclude
      that maturational changes occur in periorbital connective tissue pathways in the
      early postnatal period which make them less receptive to ingrowth by sympathetic
      nerves. The findings that connective tissue pathways are better substrates for
      sympathetic sprouting in the neonatal rat supports the view that developmental
      changes in these tissues are likely to contribute to the impaired reinnervation
      of orbital targets by contralateral neurons in juvenile and adult rats.

PMID- 9174245
TI  - Influence of BDNF on the expression of the dopaminergic phenotype of tissue used
      for brain transplants.
AB  - Brain-derived neurotrophic factor (BDNF) has previously been shown by this
      laboratory among others to promote survival and differentiation of central
      dopaminergic neurons and to stimulate expression of the dopaminergic phenotype in
      fetal cerebrocortex in vitro. We have examined the effect of BDNF antibody on
      nigral dopaminergic neurons in vivo and in vitro. It reduced the survival of rat
      fetal dopaminergic neurons in culture (up to 40% died). The BDNF antibody also
      caused ipsilateral rotation after a single in vivo intranigral injection in the
      adult rats. Pre-treatment of fetal nigral neurons with BDNF improved the
      performance of dopaminergic cells in fetal nigral transplants based on surviving
      TH+ cells numbers. Thus, parkinsonian rats receiving fetal nigral cells treated
      with BDNF showed a significantly greater reduction of turning over the 3 weeks
      following transplantation, compared with the rats receiving untreated nigral
      transplants. However, the average number of tyrosine hydroxylase (TH)-positive
      neurons in the grafts of rats receiving fetal nigral cells treated with BDNF was
      211 +/- 35 which was only about 20% of the cell number (1012 +/- 223, mean +/-
      S.E.M.) found in those receiving untreated nigral transplants. These results
      suggest that pretreatment of nigral dopaminergic neurons with BDNF may improve
      their functional performance, but not their survival in transplants. The ability
      of artificially induced cerebrocortical 'dopaminergic' cells to ameliorate
      behavioral asymmetry of Parkinsonian rats was assessed. A proportion (1.0%
      maximum) of the TH+ neurons in these transplants survived in the host brain and
      were likely to be responsible for the prominent reduction in rotation scores
      observed to occur 6 weeks after implantation. Thus, the combined treatment of
      fetal cerebral cortex with BDNF and dopamine created long-lived TH-expressing
      neuronal populations which were very effective in alleviating the rat
      parkinsonian model, and thus may be suitable for use in transplantation in
      treating human Parkinson's disease.

PMID- 9174246
TI  - Vascular endothelial growth factor mediates reactive angiogenesis in the
      postnatal developing brain.
AB  - Although chronic sublethal hypoxia has been shown to promote angiogenesis in the
      developing brain, the pathogenesis of this response is unknown. We hypothesized
      that this response may be mediated in part by vascular endothelial growth factor
      (VEGF). We reared newborn rats (P3) in a chamber with FIO2 of 9.5 +/- 1%
      (exposed, E). At P33, the animals were removed from the chamber and the brains
      prepared for immunohistochemistry, mRNA extraction, or horseradish peroxidase
      (HRP) permeability studies. We also isolated beagle brain germinal matrix
      endothelial cells from PND 1 beagle pups and placed them in three-dimensional (3
      D) coculture with PND 1 rat forebrain astrocytes. Cultures were grown for 6 days
      in 11% O2 and compared to control 3-D cocultures. When compared to age-matched
      controls, the experimental rats had significantly increased cortical vascular
      density (vessels/mm2: 518 +/- 18 vs. 400 +/- 15, P = 0.025). HRP studies
      demonstrated significantly increased permeability in all cortical vessels
      examined in experimental rats compared to controls. Compared to controls, VEGF
      mRNA from hypoxic pups was increased 2.4 times, and immunohistochemical studies
      of VEGF protein confirmed this finding. Similarly, when compared to controls,
      hypoxic cocultures of brain microvascular endothelial cells and astrocytes
      demonstrated significant increase in tubelike structures representing in vitro
      angiogenesis. Additionally, astrocyte VEGF protein levels increased 4.4-fold in
      hypoxic compared to control astrocyte cultures and VEGF protein levels increased
      1.7-fold in hypoxic compared to control cocultures. Finally, addition of VEGF (10
      ng/ml culture medium) to BBMEC alone in 3-D culture elicited not only significant
      proliferation (P = 0.001) but also increased tube formation. These data
      demonstrate that the developing brain responds to chronic sublethal hypoxia with
      increases in permeability and angiogenesis and suggest that VEGF mediates this
      response.

PMID- 9174247
TI  - Butyrylcholinesterase-positive cells of the developing chicken retina that are
      non-cholinergic and GABA-positive.
AB  - Butyrylcholinesterase (BChE) is closely related to acetylcholinesterase (AChE),
      but its function in nervous system development or physiology is unclear. Here,
      the distribution of BChE was investigated by immunohistochemical methods in the
      developing chick retina. Using a specific anti-BChE antibody, we detected
      immunoreactivity associated with different cell types in two nuclear layers and
      in plexiform layers of the retina. At embryonic day 10 (E10), a transient BChE
      staining is detected in the inner plexiform layer (IPL) and in radial cells, the
      latter possibly representing Muller glia. At E12, a subpopulation of amacrine
      cells appeared, followed by cells in the middle and outer half of the inner
      nuclear layer. These cells at locations of amacrine, bipolar and horizontal cells
      represented the predominant three cell types persisting until hatching. The BChE+
      amacrine cells were studied in more detail. Their distribution was not
      significantly different in the central and peripheral retina. Double labelling
      experiments revealed that BChE+ amacrine cells did not express choline
      acetyltransferase (ChAT), and, thus, are non-cholinergic. Only a minority of them
      coexpressed AChE. On the other hand, the majority of them colocalized with anti
      GABA immunoreactivity. Taken together, these data support a hitherto unsuspected
      role of BChE in non-cholinergic cells, possibly in conjunction with GABA.

PMID- 9174249
TI  - Prostaglandin uptake and catabolism by the choroid plexus during development in
      sheep.
AB  - We have previously reported that prostaglandin(PG) E2 levels in sheep
      cerebrospinal fluid (CSF) are high prenatally and abate rapidly after birth. This
      event may contribute to the establishment of continuous breathing. To explain
      this change, we have examined PG disposal mechanisms in the perinatal and adult
      (pregnant and non-pregnant animal) sheep brain by measuring the capacity of the
      isolated choroid plexus to concentrate [3H]PGF2alpha and [3H]PGE2. At 0.9
      gestation, [3H]PGF2alpha uptake (expressed as the tissue-to-medium ratio, T/M)
      attained a steady-state by 15 min and was maintained thereafter (T/M at 60 min,
      5.6 +/- 0.6; n = 16). Likewise, [3H]PGE2 was taken up by the tissue, but the
      actual accumulation was smaller (T/M at 60 min, 2.6 +/- 0.2; n = 8). Thin-layer
      radiochromatographic analysis of the tissue following incubation with
      [3H]PGF2alpha showed that 55 +/- 4% (n = 10) of radioactivity migrated as the 15
      keto-13,14-dihydro metabolite. [3H]PGF2alpha uptake decreased upon treatment with
      probenecid (1 mM) (T/M, 2.5 +/- 0.2; n = 10) or after adding unlabelled PGF2alpha
      to the medium (1-60 microM) (T/M at 60 microM, 1.8 +/- 0.1; n = 13). The yield of
      labelled metabolite was also lower when using excess PGF2alpha (14% of control at
      60 microM; n = 13), while it was not affected by probenecid. Uptake of both PGs
      did not change through development, from 0.7 gestation to day 18 postnatal, and
      attained higher values in the pregnant adult. Conversely, PGF2alpha catabolism
      decreased postnatally and became negligible by adult age. We conclude that during
      the perinatal period PGs can be removed from CSF by two distinct processes in the
      choroid plexus, active transport and catabolism. Neither process, however, can
      account for the birth-related change in CSF PGE2.

PMID- 9174248
TI  - Metabolism of [5-(3)H]kynurenine in the developing rat brain in vivo: effect of
      intrastriatal ibotenate injections.
AB  - Two metabolites of the kynurenine pathway of tryptophan degradation, the
      neurotoxin quinolinic acid (QUIN) and the neuroprotectant kynurenic acid (KYNA),
      may play a role in the initiation or propagation of brain diseases. In order to
      study their disposition during the acute and chronic stages of neurodegeneration,
      effects of an excitotoxic insult on the de novo synthesis of several kynurenine
      pathway metabolites were examined in vivo. Neuronal injury and lesions were
      produced in 7-day (PND 7), 14-day (PND 14) and young adult rats by an
      intrastriatal injection of the excitotoxin ibotenic acid. At 2 h, 2, 7 and 28
      days later, the formation of tritiated KYNA, 3-hydroxykynurenine (3HK),
      xanthurenic acid and QUIN was assessed after an acute intrastriatal injection of
      their common bioprecursor, [5-(3)H]kynurenine. In all three age groups, the acute
      insult resulted in a shift towards enhanced KYNA formation, as indicated by 2-4
      fold decreases in the 3HK/KYNA and QUIN/KYNA ratios in ibotenate-treated striata.
      At later post-lesion intervals, age-specific several-fold changes were observed
      in the flux through both the KYNA and QUIN branches of the kynurenine pathway.
      With aging, kynurenine conversion to QUIN and especially to 3HK, became
      increasingly more prominent, though KYNA synthesis was substantially activated as
      well. The acute toxin-induced changes in kynurenine metabolism, the propensity of
      the lesioned immature striatum to increase KYNA production preferentially, and
      the pronounced lesion-induced long-term increases in cerebral KYNA, 3HK and QUIN
      formation may participate in the modulation of NMDA receptor function following
      injury. In particular, changes in the production of these kynurenine pathway
      metabolites may play a role in mechanisms involved in endogenous neuroprotection,
      delayed neurodegeneration and regenerative processes.

PMID- 9174250
TI  - Alpha2B adrenoceptor mRNA expression during rat brain development.
AB  - The expression of alpha2B adrenoceptor mRNA in developing and adult rat brain was
      examined, using in situ hybridization with S-labeled riboprobes. In the adult we
      have detected more widespread expression than previously reported, with moderate
      to strong hybridization signals in the fundus striati, olfactory tubercles,
      septum, thalamus and Purkinje cells of the cerebellum. In addition, there was low
      expression in the endopiriform nucleus, claustrum, cortex, caudate-putamen and
      spinal trigeminal nucleus of the brain stem. During embryonic development, there
      was intense, transient mRNA expression in the developing vascular plexus and
      vasculature which disappeared by birth. In most brain areas which exhibit mRNA
      expression in the adult, expression started during late embryonic development;
      with the exception of the thalamus, where expression was differentially regulated
      in sensory and non-sensory thalamic nuclei starting at the end of the first
      postnatal week. In addition, there was transiently upregulated expression in the
      caudate-putamen and cerebellar Purkinje cells during late embryonic and early
      postnatal development, respectively. This transient expression correlates with
      the time of neuronal migration and differentiation in these structures and
      complements the developmental expression of alpha2A and alpha2C adrenoceptors.
      These results suggest that alpha2B adrenoceptors may play a role in angiogenesis
      and in mediating neurotrophic functions of norepinephrine in some brain areas.

PMID- 9174251
TI  - Calretinin immunoreactivity in the developing olfactory system of the rainbow
      trout.
AB  - The distribution of calretinin immunoreactivity in the developing olfactory
      system of the rainbow trout was studied by using an indirect immunocytochemical
      method. Calretinin immunoreactivity was firstly detected at 150 day-degrees in
      the olfactory placode, where labeled primordial cells were observed. At 250 day
      degrees, precursor cells of the olfactory receptor neurons located in the
      olfactory pit were calretinin-immunoreactive. At 300 day-degrees, recognizable
      olfactory receptor neurons displayed calretinin immunoreactivity in the olfactory
      epithelium, and calretinin-immunopositive olfactory axons reached the presumptive
      olfactory bulb. After hatching (400 day-degrees) and during the subsequent
      development and maturation of the olfactory system, the number of calretinin
      immunopositive olfactory receptor cells increased and distributed homogeneously
      throughout the olfactory epithelium. Accordingly, new positive olfactory fibers
      arrived to the olfactory bulb arborizing in olfactory glomeruli distributed in
      nine different terminal fields. Six days after hatching, calretinin
      immunopositive interneurons within the olfactory bulb were also observed. The
      size and number of calretinin-immunoreactive interneurons increased from this
      stage to adulthood. The adult pattern demonstrated both similarities and
      differences with the distribution of calretinin immunoreactivity previously
      described in the olfactory system of mammals.

PMID- 9174252
TI  - Induction of myelin-associated glycoprotein expression through neuron
      oligodendrocyte contact.
AB  - The role of neurons on expression of myelin-associated glycoprotein (MAG) in
      oligodendrocytes and oligodendroglial differentiation was examined. Primary
      cultures of oligodendrocytes prepared from neonatal mouse brains were co-cultured
      with neuronal cells derived from embryonal carcinoma P19 cells. The levels of MAG
      mRNAs following this co-culture were determined by reverse transcription (RT)
      PCR. In oligodendrocytes co-cultured in direct contact with P19-derived neurons,
      the levels of MAG mRNAs, particularly that of the L-type isoform, were markedly
      higher than those in cultures without any neuronal cells. On the other hand, when
      the P19-derived neurons were present, but not in direct contact, no significant
      induction of MAG expression was found, though oligodendrocytes appeared to mature
      morphologically. The L-MAG expression was also stimulated when just the neuronal
      cell membrane fraction was added, which implies that there might be some
      effecter(s) in the cell membrane which are possibly exerting a signal
      transduction for myelin formation. These results suggest that morphological
      differentiation and functional maturation of oligodendrocytes are due to
      independent factors. The former is caused by some humoral factor(s) liberated
      from neuronal cells, while the latter resulted from cellular contact with
      neuronal cells.

PMID- 9174253
TI  - Calbindin-D28k is regulated by adrenal steroids in hypothalamic tissue during
      prenatal development.
AB  - Regulation of calbindin-D28k (CALB) in the medial basal hypothalamus (MBH) from
      male and female fetuses was examined by Western analysis. Control fetal males
      displayed significantly higher MBH CALB levels compared to females at gestational
      day 20. Whereas, in general, the lowest CALB levels were recorded in male and
      female fetuses from long-term prenatally stressed or fetuses from
      adrenalectomized pregnant rats. These data indicate that corticosterone regulates
      MBH CALB expression during prenatal development and CALB may be implicated in
      modulating the sexual differentiation of neural structures within the MBH during
      perinatal development.

PMID- 9174254
TI  - Absence of oculomotor and trochlear motoneurons leads to altered extraocular
      muscle development in the Wnt-1 null mutant mouse.
AB  - Wnt-1 null mutant mice lack midbrain somatic motor nuclei. Primordial migration
      and spatial patterning of the extraocular muscles, however, was preserved, but
      myogenesis was disrupted in aneural muscles. Some muscles normally innervated by
      oculomotor and trochlear nuclei received aberrant innervation, which proved
      sufficient to maintain prenatal stages of myogenesis. The absence of motoneurons
      followed by innervation from inappropriate motoneuron pools is a viable candidate
      mechanism in ocular motility disorders, including Duane retraction syndrome and
      congenital fibrosis of extraocular muscle.

PMID- 9174255
TI  - Cell size in the lateral geniculate nucleus of cats reared with esotropia and
      sagittal transection of the optic chiasm.
AB  - We have attempted to investigate the role of extraretinal influences in
      controlling visual system development by rearing cats with esotropia in
      combination with sagittal transection of the optic chiasm. This combination leave
      two intact A1 laminae, one innervated by the deviated eye and one innervated by
      the unoperated eye and thus minimizes the contributions of retinally mediated
      influences. Cell size measurements in the dorsal lateral geniculate nucleus
      revealed that the neurons in the A1 lamina innervated by the deviated eye were,
      on average, 10-15% smaller than their counterparts in the contralateral A1
      lamina.

PMID- 9174256
TI  - Dopamine D1 and D2 antagonists block L-DOPA-induced air-stepping in decerebrate
      neonatal rats.
AB  - L-DOPA administered to neonatal rats suspended in air elicits stereotypic
      locomotor activation termed air-stepping; it can be dose-dependently blocked by a
      dopamine (DA) D1 or D2 antagonist. In order to determine whether the forebrain is
      the site for this blockade, decerebrate 5-day-old rats were pretreated
      subcutaneously with either the DA D1 receptor antagonist SCH 23390 (16 mg/kg),
      the DA D2 receptor antagonist spiperone (6 mg/kg), or vehicle before receiving
      100 mg/kg L-DOPA. Both antagonists blocked L-DOPA-induced air-stepping in both
      decerebrate and intact pups.

PMID- 9174257
TI  - Profile of glutamylated tubulin expression during cerebellar granule cell
      development in vitro.
AB  - The developmental regulation of tubulin and several of its posttranslational
      modifications was examined during the differentiation of rat cerebellar granule
      cells in vitro. In particular, we have noted that the glutamylation of alpha- and
      beta-tubulin subunits varies during development and becomes more prominent in
      differentiating neuronal processes. These results indicate that glutamylation of
      tubulin may be important in the stabilization of microtubules during the
      maturation of the neuronal cytoskeleton.

PMID- 9174258
TI  - The effects of bupropion in vivo in the neostriatum of 5-day-old and adult rats.
AB  - Infusion of six concentrations of the dopamine uptake inhibitor bupropion into
      the neostriatum increased extracellular dopamine in a dose-dependent manner in 5
      day-old and adult rats. There was no age-related difference when calculated as a
      percentage of predrug dopamine baseline levels, but the absolute increase of
      dopamine was greater in the adult rats. Bupropion had only a minor effect on
      extracellular levels of DOPAC.

PMID- 9174259
TI  - Transient developmental expression of CD15 in the motor and auditory cortex of
      the mouse.
AB  - The distribution of the glycoprotein CD15 (FAL, SSEA-1, Le(x)) in the developing
      cortex of the mouse has been examined by immunohistochemistry of paraffin
      sections. The pattern of CD15 immunoreactivity was observed to occur in 4 stages.
      In the first stage, the presumptive subplate region in the lateral and rostral
      parts of the developing isocortex was transiently labelled at E12. In the second
      stage, between E13 and E17, very faint label was found only in the ventricular
      germinal zone, possibly within radial glial fibres. The third stage began at E18,
      when transient labelling of several discrete cortical areas was apparent; the
      motor cortex (from E18 to P3), an area in the temporal lobe (presumptive primary
      auditory cortex; from E18 to P5.5) and the piriform and entorhinal cortices (from
      E18 to P3). The final stage began at P2, when a mosaic camouflage pattern of
      labelling started to appear throughout the developing cortex, particularly in
      layer I. The distribution of the transient label in the motor cortex during the
      perinatal period suggests that it may be associated with early events in
      corticospinal or other projection neuron maturation (apical dendrite growth and
      differentiation). The labelling in the presumptive auditory cortex (Te1) may also
      be involved in the differentiation of neurons in the upper cortical plate.

PMID- 9174260
TI  - Methods of analysis of chiral non-steroidal anti-inflammatory drugs.
AB  - Although the analysis of the enantiomers of chiral non-steroidal anti
      inflammatory drugs (NSAIDs) has been carried out for over 20 years, there often
      remains a deficit within the pharmaceutical and medical sciences to address this
      issue. Hence, despite world-wide therapeutic use of chiral NSAIDs the importance
      of stereoselectivity in pharmacokinetic, pharmacodynamic and pharmacological
      activity and disposition has often been ignored. This review presents both the
      general principles that allow separation of chiral NSAID enantiomers, and
      discusses both the advantages and disadvantages of the available chromatographic
      assay methods and procedures used to separately quantify NSAID enantiomers in
      biological matrices.

PMID- 9174261
TI  - Determination of the lipid peroxidation product (E)-4-hydroxy-2-nonenal in
      clinical samples by gas chromatography--negative-ion chemical ionisation mass
      spectrometry of the O-pentafluorobenzyl oxime.
AB  - (E)-4-Hydroxy-2-nonenal (HNE) is a highly reactive product of the free radical
      stimulated lipid peroxidation of phospholipid-bound arachidonic acid in cellular
      membranes. We describe a sensitive and specific method for the determination of
      HNE in clinical samples. The method is based on the formation of the O
      pentafluorobenzyl (O-PFB) oxime derivative of HNE, which is then extracted and
      cleaned up by solid-phase extraction. The HNE O-PFB oxime is then analysed
      without further derivatisation by capillary column gas chromatography-negative
      ion chemical ionisation mass spectrometry (GC-NICI-MS) using selected-ion
      monitoring. Concentrations down to the pmol range were achieved using deuterated
      HNE as an internal standard. The method was used to determine HNE in the
      cerebrospinal fluid and plasma of patients with Parkinson's disease, the plasma
      of patients with HIV-1 infection and AIDS and in inflamed mucosal biopsy
      specimens from patients with inflammatory bowel disease.

PMID- 9174262
TI  - Determination of dimethylamine in biological samples by high-performance liquid
      chromatography.
AB  - A reversed-phase HPLC method for the quantification of dimethylamine in serum and
      urine is presented. Dimethylamine (DMA) is converted into a stable fluorescent
      product by precolumn derivatization with fluorenylmethylchloroformate. The DMA
      derivative is resolved from derivatives of other amines and amino acids by
      gradient elution with a total run-time of 15 min. The lower limit of
      determination in biological samples is 0.1 micromol/l. Recoveries from spiked
      serum samples were 99-107%. Within- and between-run precision were better than
      6%. Concentrations of DMA in serum from normal human subjects (n=8) and from
      continuous ambulatory peritoneal dialysis patients (n=15) were 3.3+/-1.5 and
      29.1+/-12.1 micromol/l, respectively.

PMID- 9174263
TI  - Determination of agmatine in brain and plasma using high-performance liquid
      chromatography with fluorescence detection.
AB  - Decarboxylated arginine, agmatine, is a neurotransmitter candidate for
      imidazoline receptors. A method is described to measure agmatine in rat brain and
      human plasma by isocratic high-performance liquid chromatography (HPLC) with
      fluorescence detection and o-phthalaldehyde derivatization. Quantitation is based
      on the method of additions of internal agmatine spikes. This assay has
      sensitivity in the low picomole range and a detection limit of 100 fmol. The
      correlation coefficient for the agmatine standard curve was 0.999+/-0.001 S.D.,
      and intra- and inter-assay C.V.s were less than 8%. The accuracy of our isocratic
      method compared favorably with a gradient HPLC protocol, originally developed for
      bacterial agmatine, which we modified for use with tissues. Agmatine
      concentrations in rat brain were proportioned similarly to the regional
      distribution of imidazoline-1 receptors. These methods can be used as reliable
      research tools in various biological samples.

PMID- 9174265
TI  - Rapid method for the isolation of hydroxylysylpyridinoline and lysylpyridinoline
      from concentrated bone hydrolysates by liquid chromatographic techniques.
AB  - A rapid method for the isolation of hydroxylysylpyridinoline and lysylyridinoline
      from bone by liquid chromatographic methods is described. Decalcified bone is
      hydrolysed in 7 M hydrochloric acid. After evaporation of the acid, the high
      molecular mass and dark coloured degradation products are removed by adsorption
      on non-polar adsorbents. The pyridinolines are separated from the majority of the
      amino acids by adsorption on cellulose. Separation of HP and LP is performed
      either by cation-exchange chromatography or by reversed-phase ion-pair
      chromatography. The pyridinoline containing fractions are desalted by size
      exclusion chromatography. The progress of the hydrolytic cleavage of collagen and
      the optimal parameters for purification and separation were examined. As a result
      the existing method allows the isolation of high amounts of pyridinolines with
      low amounts of adsorbents and chemicals within a short time.

PMID- 9174264
TI  - Isolation and quantitation of isotopically labeled amino acids from biological
      samples.
AB  - To face the problem of simultaneous isolation and quantitation of isotopically
      labeled amino acids in biological samples, two semi-preparative chromatographic
      methods were developed. One method was especially designed to isolate
      radioactively labeled amino acids for which we used derivatization with the
      fluorophore o-phthaldialdehyde (OPA), which is known to be easy and reliable.
      Isolation of amino acids labeled with stable isotopes required another approach
      as we wanted to use isotope ratio mass spectroscopy (IRMS), which can only be
      performed on pure, non-derivatized amino acids. Because the OPA probe cannot be
      removed after isolation of the derivative, we used 9-fluorenylmethylchloroformate
      (FMOC) instead. This probe is linked to an amino acid via a peptide bond which
      can easily be broken by gas-phase acid hydrolysis (103% recovery after 5 h at 150
      degrees C: S.D=3.5%, n=14). Run time (injection to injection) was 60 min for the
      OPA method and 75 min for the FMOC method. Both fluorescence and UV absorbance
      detection can be employed. The coefficient of variation (C.V.) for peak area
      measurement was below 2% for most OPA amino acids and below 3% for most FMOC
      amino acids. At maximum, a total of 1000 microl could be injected, representing
      approximately 200 microl of deproteinized plasma. The methods were linear up to
      injection of 0.5 micromol of all amino acids (OPA: r2=0.995-0.999; FMOC: r2=0.992
      0.999). The C.V. of the IRMS measurement within the range which can be isolated
      maximally in one chromatographic run (50-500 nmol), was less than 3% above 100
      nmol, indicating that chromatographic isolation fulfils the needs of the IRMS
      determination. The resulting methods are suitable for the isolation and
      quantitation of micromolar amounts of labeled amino acids from biological
      samples.

PMID- 9174266
TI  - Development and validation of an ion-pair reversed-phase high-performance liquid
      chromatographic method for the separation of phosphonodipeptides.
AB  - The objective of this research was to develop a rapid, sensitive and reliable
      method for the separation of phosphonodipeptide prodrugs and parent compounds to
      facilitate the evaluation of cell permeation using in vitro cell culture models.
      Separation was accomplished isocratically within 10.0 min using a C18 (150x4.6 mm
      I.D., 3 microm) reversed-phase column. The mobile phase consisted of 5 mM
      tetrahexyl ammonium (ion-pair reagent) in 0.02 M phosphate buffer pH 6.5
      acetonitrile (48.5:51.5, v/v). The flow-rate was 1.1 ml/min with detection at 221
      nm. The standard curves were linear (r2>0.999) over the concentration range 1-100
      microM. The method was reliable and reproducible, with the limit of quantitation
      being 1 microM (25 ng on column).

PMID- 9174267
TI  - Simplified method for the determination of 25-hydroxy and 1alpha,25-dihydroxy
      metabolites of vitamins D2 and D3 in human plasma. Application to nutritional
      studies.
AB  - A simplified method for the determination of 25-hydroxy and 1alpha,25-dihydroxy
      metabolites of vitamins D2 and D3 in human plasma was developed. Plasma samples
      were deproteinizated and applied to a Bond Elut C18OH cartridge to separate 25
      hydroxyvitamin D (25-OH-D) and 1alpha,25-dihydroxyvitamin D [1,25(OH)2D]
      fractions. The 25-OH-D fraction was purified by a Bond Elut C18 cartridge and 25
      OH-D2 and 25-OH-D3 were assayed by HPLC using a Zorbax SIL column. The 1,25(OH)2D
      fraction obtained above was subsequently applied to HPLC using a Zorbax SIL
      column to separate 1,25(OH)2D2 and 1,25(OH)2D3 fractions which were determined by
      a radioreceptor assay (RRA) using calf thymus receptor. The method was applied to
      nutritional studies.

PMID- 9174268
TI  - Individual variation of human plantar stratum corneum lipids, determined by
      automated multiple development of high-performance thin-layer chromatography
      plates.
AB  - The stratum corneum lipids are unique in composition and have been used
      frequently as a model system of the skin's lipid barrier. Automated multiple
      development (AMD) of high-performance thin-layer chromatography plates in
      combination with a 25-step gradient, based on methanol, diethyl ether and n
      hexane separated the six major human plantar stratum corneum lipids. Post
      chromatographic staining of these lipids with a solution of MnCl2-H2SO4 at 130
      degrees C or a solution of CuSO4-H3PO4 at 140 degrees C allowed visualization of
      the lipids and quantification. The MnCl2-H2SO4 solution stained saturated fatty
      acids less intensely. Therefore, the CuSO4-H3PO4 solution was used for
      quantification and we found, on average, 2.06% (w/w) cholesterol 3-sulphate,
      20.16% (w/w) free fatty acids, 20.25% (w/w) ceramides, 43.53% (w/w) non
      esterified sterols, 4.56% (w/w) triacylglycerols and 9.4% (w/w) sterolesters in
      the human plantar stratum corneum extracts. The concentration of phospholipids
      was less than 1% (w/w). In addition, the lipid composition of twenty different
      human plantar stratum corneum extracts was determined. Statistics revealed a
      correlation between the ratio of free fatty acids and non-esterified sterols
      (r=0.832, p<0.01, n=20). Several control experiments proved that this correlation
      is not due to the extraction method, the post-chromatographic staining procedure
      or bacterial contamination of the stratum corneum.

PMID- 9174269
TI  - Determination of hexahydrophthalic acid and methylhexahydrophthalic acid in
      plasma after derivatisation with pentafluorobenzyl bromide using gas
      chromatography and mass spectrometric detection.
AB  - A method for the simultaneous determination of hexahydrophthalic acid (HHP acid)
      and methylhexahydrophthalic acid (MHHP acid) in human plasma was developed. The
      procedure was a rapid, single step extractive derivatisation with
      pentafluorobenzyl bromide as the derivatisation agent. The formed
      pentafluorobenzyl esters were analysed by gas chromatography-mass spectrometry in
      negative ion chemical ionisation mode with ammonia as the moderating gas.
      Deuterium-labeled HHP acid and MHHP acid were used as internal standards. The
      detection limit was 0.4 ng/ml for HHP acid (m/z 153) and 0.3 ng/ml for MHHP acid
      (m/z 365). The within-day precision of the method was between 2 and 3% and the
      between-day precision was between 3 and 12%. The overall recovery was between 65
      and 83%. A comparison between HHP acid determinations with a previous and this
      method showed that the methods gave similar results. The method was applicable
      for analysis of plasma from occupationally exposed workers.

PMID- 9174270
TI  - 32P-Postlabeling high-performance liquid chromatographic improvements to
      characterize DNA adduct stereoisomers from benzo[a]pyrene and
      benzo[c]phenanthrene, and to separate DNA adducts from 7,12
      dimethylbenz[a]anthracene.
AB  - Single compounds can generate complex DNA adduct patterns by reactions through
      different pathways, with different target nucleotides and through different
      configurations of the products. DNA adduct analysis by 32P-HPLC was improved by
      adding an isocratic plateau in an otherwise linear gradient, thereby enhancing
      resolution of predictable retention time intervals. This enhanced 32P-HPLC
      technique was used to analyze and at least partly resolve 14 out of 16 available
      benzo[c]phenanthrene deoxyadenosine and deoxyguanosine adduct standards, 8 out of
      8 available benzo[a]pyrene deoxyadenosine and deoxyguanosine adduct standards,
      and 51 peaks from 7,12-dimethylbenz[a]anthracene-calf thymus DNA reaction
      products. The same type of gradient modifications could be used to enhance
      resolution in analyses of other complex DNA adduct mixtures, e.g., in vivo in
      humans.

PMID- 9174271
TI  - Determination of Aconitum alkaloids in blood and urine samples. I. High
      performance liquid chromatographic separation, solid-phase extraction and mass
      spectrometric confirmation.
AB  - Determination of four toxic Aconitum alkaloids, aconitine, mesaconitine,
      hypaconitine and jesaconitine, in blood and urine samples has been established
      using high-performance liquid chromatography (HPLC) combined with ultraviolet
      absorbance detection, solid-phase extraction and mass spectrometry (MS). These
      alkaloids were hydrolyzed rapidly in alkaline solution (half lives (t1/2)<one
      day), were stable in solutions of acetonitrile, tetrahydrofuran and diluted
      hydrochloric acid (t1/2>five months) and were unstable in solutions of methanol
      and ethanol (t1/2<one month). These alkaloids were separated on an
      octadecylsilica column with isocratic elution using a solvent mixture of
      tetrahydrofuran and 0.2% trifluoroacetic acid (14:86, v/v), which was found to be
      the optimal solvent of the elution systems examined. Calibration curves with UV
      detection were linear on injection of amounts ranging from 2.5 to 500 ng, and the
      limit of detection was 1 ng (S/N=3). These four alkaloids in aqueous solution
      were recovered almost totally by solid-phase extraction using the styrene polymer
      resin, Sep-Pak Plus PS-1, and were eluted using a mixture of acetonitrile and
      hydrochloric acid. These Aconitum alkaloids were confirmed by HPLC coupled with
      fast atom bombardment MS, giving their protonated molecular ions as base peaks.
      These alkaloids were detected by HPLC with UV detection from blood samples spiked
      with more than 50 ng ml(-1) of alkaloids, but were not detectable from urine
      samples spiked with 5 microg ml(-1) of alkaloids because of severe sample
      interference.

PMID- 9174272
TI  - Quantitative multi-residue determination of beta-agonists in bovine urine using
      on-line immunoaffinity extraction-coupled column packed capillary liquid
      chromatography-tandem mass spectrometry.
AB  - This report demonstrates the potential of on-line immunoaffinity extraction and
      coupled column packed capillary liquid chromatography-ion spray tandem mass
      spectrometry for multi-residue determination of five beta-agonists, clenbuterol,
      mabuterol, mapenterol, methylclenbuterol, and tolubuterol, in bovine urine using
      an automated column switching system. Trace enrichment and preliminary sample
      cleanup was performed on-line using bovine urine diluted with phosphate-buffered
      saline. The column switching process involves trapping the target analytes onto a
      mini-bore immunoaffinity column, whereupon the target analytes are released from
      the immunoaffinity column onto a trapping column and subsequently eluted onto a
      packed capillary analytical column. The latter packed capillary column was used
      to provide the optimum sensitivity for ion spray LC-MS-MS analyses. The three
      column system consists of a 2.0 mm I.D. immunoaffinity column, a 1 mm I.D.
      reversed-phase trapping column and a 320 microm I.D. packed capillary analytical
      column. Both qualitative and quantitative results are presented for the multi
      residue determination of the target beta-agonists from the complex urinary
      matrix. Using tolubuterol as an internal standard, the quantitative data showed
      good linear response within the concentration ranges studied. Lower levels of
      quantitation were 50 part per trillion (ppt) for clenbuterol and
      methylclenbuterol, 20 ppt for mabuterol and 10 ppt for mapenterol. The bovine
      renal elimination is described using the technique for one of the beta-agonists,
      clenbuterol. The concentration of clenbuterol was detectable 15 days after the
      cessation of oral administration.

PMID- 9174273
TI  - Manual and automatic extraction and high-performance liquid chromatographic
      determination of a spicamycin derivative, KRN5500, in rat plasma.
AB  - A sensitive reliable method for the extraction, separation and quantitation of
      KRN5500 (I), a spicamycin derivative, from rat plasma was developed. It involves
      solid-phase extraction of the drug using a Bond Elut C18 cartridge and reversed
      phase HPLC on a YMC-Pack ODS column with an ultraviolet detector. The intra- and
      inter-assay coefficients of variation by manual (n=10) and automatic (n=5)
      extraction were less than 9 and 13% and 6 and 8%, respectively. The limit of
      quantitation of each extraction procedure was 2 ng potency/ml. This extraction
      method may thus be considered useful for monitoring I in animals following its
      administration.

PMID- 9174274
TI  - Determination of gentamicin in bovine milk using liquid chromatography with post
      column derivatization and fluorescence detection.
AB  - A method capable of separating and quantifying the three major and one minor
      components of gentamicin in milk has been developed. The method is capable of
      detecting 15 ng/ml gentamicin, based on a total of the four components. Milk
      samples are centrifuged at 4 degrees C, the fat layer removed, and the samples
      deproteinated with 30% trichloracetic acid. After a second centrifugation, the
      supernatant is passed through a C18 solid-phase extraction column. The column is
      washed with water, water-methanol (50:50) and methanol. Ammonium hydroxide (16%)
      in methanol is used to elute the gentamicin. The eluent is evaporated to near
      dryness and taken up with water. An aliquot of the sample is then mixed with an
      ion-pairing reagent for chromatography. Separation is achieved using
      pentanesulfonic acid in a water-methanol mobile phase on a C18 reversed-phase
      column. The o-phthalaldehyde fluorescence derivatives of gentamicin are formed
      post-column and are detected with excitation at 340 nm and emission at 430 nm.
      The percent recovery of gentamicin averaged 72, 78 and 88% from milk samples
      fortified at 15, 30 and 60 ng/ml, respectively.

PMID- 9174275
TI  - Automated high-performance liquid chromatographic method for the analysis of two
      novel ergoline compounds in human plasma.
AB  - A rapid and sensitive high-performance liquid chromatographic method for the
      determination of the novel ergoline derivatives sergolexole (compound I), its
      acid metabolite (compound II) and cis-n-(2-hydroxycyclopentyl)-6-methyl-1-(1
      methylethyl)ergoline-8- carboxamide (LY215840, compound III) in human plasma is
      reported. The compounds were extracted from plasma by automated solid-phase
      extraction and analysed on a reversed-phase C8 column with fluorescence
      detection. The limit of quantification for all compounds was 10 ng/ml and the
      response was linear over the range 10-1000 ng/ml. Validation studies showed the
      method to be both repeatable and reproducible with no interference from human
      plasma. The method has been used to support pharmacokinetic studies and has
      proved to be robust and effective.

PMID- 9174276
TI  - High-performance liquid chromatographic determination of the conjugate
      metabolites of moxisylyte in human plasma and urine.
AB  - Sensitive and specific high-performance liquid chromatographic methods with
      fluorescence detection are described for the determination of the metabolites of
      moxisylyte (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methylphenyl acetate) in
      human plasma and urine. Deacetylmoxisylyte glucuroconjugate (DAM-G) was
      hydrolysed enzymatically using 1-glucuronidase and quantified as the difference
      between the DAM concentrations determined after and before hydrolysis. The two
      sulphate derivatives (deacetylmoxisylyte sulphoconjugate, DAM-S and
      monomethyldeacetylmoxisylyte sulphoconjugate, MDAM-S), were analysed without
      prior hydrolysis. Their extraction from plasma and urine, as well as that of DAM
      from plasma, involved the use of C18 cartridges adapted on a Benchmate
      workstation. DAM in urine was quantified after liquid-liquid extraction. The two
      methods were validated for specificity, linearity, intra- and inter-day precision
      and accuracy. Precision was generally < or = 15% and accuracy < or = 12%. In
      plasma, the limits of quantification were 2.5 ng/ml for DAM and 2.8 ng/ml for the
      two sulphates, in urine, they were 40 ng/ml for DAM and 200 ng/ml for the
      sulphates. These methods were used for pharmacokinetic studies in healthy
      subjects.

PMID- 9174277
TI  - Oral platelet aggregation inhibitor Ro 48-3657: determination of the active
      metabolite and its prodrug in plasma and urine by high-performance liquid
      chromatography using automated column switching.
AB  - A sensitive and highly automated high-performance liquid chromatography (HPLC)
      column-switching method has been developed for the simultaneous determination of
      the active metabolite III and its prodrug II, both derivatives of the oral
      platelet inhibitor Ro 48-3657 (I), in plasma and urine of man and dog. Plasma
      samples were deproteinated with perchloric acid (0.5 M), while urine samples
      could be processed directly after dilution with phosphate buffer. The prepared
      samples were injected onto a pre-column of a HPLC column switching system. Polar
      plasma or urine components were removed by flushing the precolumn with phosphate
      buffer (0.1 M, pH 3.5). Retained compounds (including II and III) were
      backflushed onto the analytical column, separated by gradient elution and
      detected by means of UV detection at 240 nm. The limit of quantification for both
      compounds was 1 ng/ml (500 microl of plasma) and 25 ng/ml (50 microl of urine)
      for plasma and urine, respectively. The practicability of the new method was
      demonstrated by the analysis of about 6000 plasma and 1300 urine samples from
      various toxicokinetic studies in dogs and phase 1 studies in man.

PMID- 9174278
TI  - High-performance liquid chromatographic determination of carbamazepine and
      metabolites in human hair.
AB  - To study the use of hair analysis in monitoring drug compliance and historical
      changes in pharmacokinetics we developed a method for the quantitative
      determination of the anti-epileptic drug carbamazepine (CBZ) and trans-10,11
      dihydro-10,11-dihydroxy-carbamazepine (CBZ-diol) in hair from carbamazepine
      users. Digestion by 1 M NaOH was found to be the best method for isolating CBZ
      and CBZ-diol from hair, followed by solid-phase extraction and reversed-phase
      HPLC with UV detection. Recoveries from spiked hair samples were 76-86%. Within
      day precision (C.V.; n = 10) for CBZ and CBZ-diol in hair of a CBZ user
      containing 10.9 microg/g CBZ and 3.2 microg/g CBZ-diol were 1.7 and 5.0%,
      respectively. Sectional hair analysis of a patient on a constant dosage of CBZ
      demonstrates an exponential decrease in hair concentrations of CBZ and CBZ-diol
      with increasing distance from the root, probably caused by shampooing. No CBZ
      10,11-epoxide (CBZ-epox) could be detected. However, one component in the
      chromatogram is probably CBZ-beta-hydroxythioether, an adduct of CBZ-epox with
      cysteine, or acridinethioacetal, its rearrangement product. The concentration of
      this component does not decrease with increasing distance from the root.

PMID- 9174279
TI  - Rapid quantitation of (-)-2'-deoxy-3'-thiacytidine in human serum by high
      performance liquid chromatography with ultraviolet detection.
AB  - A rapid, sensitive and specific high-performance liquid chromatographic (HPLC)
      assay was developed and validated for the measurement of (-)-2'-deoxy-3'
      thiacytidine (3TC) in human serum. The method included precipitation of serum
      proteins by trichloroacetic acid (20%, w/v) treatment followed by centrifugation.
      The resulting supernatant was directly injected and 3TC was isocratically
      chromatographed on a reversed-phase C18 column using a mixture of phosphate
      buffer and methanol (88.3:11.7. v/v) and monitored at 280 nm. The limit of
      quantitation was 20 ng/ml using 100 microl of serum. The standard curve was
      linear within the range of 20-10,000 ng/ml. Replicate analysis of three quality
      control samples (40-1500 ng/ml) led to satisfactory intra- and inter-assay
      precision (coefficient of variation from 3.0 to 12.9%) and accuracy (deviation
      from 6.3 to 9.7%). Moreover, sample treatment processes including human
      immunodeficiency virus (HIV) heat-inactivation, exposure at room temperature and
      freezing-thawing cycles did not influence the stability of the analyte. This
      assay was successfully applied to the determination of 3TC serum levels in HIV
      infected patients. In addition, preliminary results indicated that this procedure
      may also be extended to the measurement of 3TC in human plasma and urine.

PMID- 9174280
TI  - High-performance liquid chromatographic determination of (-)-beta-D-2-aminopurine
      dioxolane and (-)-beta-D-2-amino-6-chloropurine dioxolane, and their metabolite (
      )-beta-D-dioxolane guanine in monkey serum, urine and cerebrospinal fluid.
AB  - (-)-beta-D-2-Aminopurine dioxolane (APD), (-)-beta-D-2-amino-6-chloropurine
      dioxolane (ACPD) and dioxolane guanine (DXG) are nucleoside analogues possessing
      potent activity against human immunodeficiency virus (HIV) and hepatitis B virus
      (HBV) in vitro. APD and ACPD are metabolized in vivo to yield DXG. Reversed-phase
      HPLC analytical methodologies were developed for the simultaneous determination
      of APD and DXG, and for ACPD and DXG in monkey serum, urine and cerebrospinal
      fluid (CSF). 2-Fluoro-2',3'-dideoxyinosine (FDDI) served as the internal
      standard. The extraction recoveries of the nucleoside analogues from serum
      samples were similar, averaging approximately 90%. The limit of quantitation of
      the analytical method for serum samples was 0.1 microg/ml for DXG, and 0.25
      microg/ml for APD and ACPD. The intra- and inter-day relative standard deviations
      for each compound at low, medium and high nucleoside concentrations were less
      than 9.0%. The accuracy of the assay methods was greater than 90% for prodrugs
      and parent compound. Similar results were observed with urine and CSF samples.
      Thus, these methods provide sensitive, accurate and reproducible determination of
      the prodrugs and parent nucleoside in biological samples.

PMID- 9174282
TI  - Determination of a new antifungal agent, voriconazole, by multidimensional high
      performance liquid chromatography with direct plasma injection onto a size
      exclusion column.
AB  - A fully automated method has been developed for the analysis of a new antifungal
      agent, voriconazole, in human plasma. Multidimensional chromatography was used
      with size-exclusion chromatography as the first step to separate plasma protein
      from the drug and internal standard which were then trapped on a precolumn of
      pellicular ODS. A reversed-phase column, Spherisorb ODS2, then separated drug and
      internal standard from one another and from remaining plasma components. With an
      injection of 0.56 ml plasma the limit of quantitation of the method was 5 ng/ml.

PMID- 9174281
TI  - Studies on the pharmacological properties of novel arylene bis(methylketone)
      compounds using solid-phase extraction and high-performance liquid
      chromatography.
AB  - A method utilising solid-phase extraction followed by high-performance liquid
      chromatography has been developed to quantify novel arylene bis(methylketone)
      chemotherapeutics present in biological samples. The samples are extracted over
      cyanopropylsilane solid-phase extraction cartridges using 10 mM heptanesulfonate
      10 mM tetramethylammonium chloride-4.2 mM H3PO4-95% CH3CN as the eluent.
      Analytical chromatography utilises a diisopropyl-C8 reversed-phase column and a
      7.5-45% CH3CN gradient in 10 mM heptanesulfonate-10 mM tetramethylammonium
      chloride-4.2 mM H3PO4-H2O. Detection was by ultraviolet spectrophotometry at 300
      or 240 nm. The linear response of the assay was found to extend from at least 100
      microg/ml down to 97.66 ng/ml for a 100 microl injection. The assay system was
      utilised to determine the plasma kinetics of the compounds in mice, where all the
      drugs were found to display rapid absorption and elimination following
      intraperitoneal dosing. In vitro and in vivo studies of metabolism demonstrated
      that each of the compounds produced several metabolites, and that this conversion
      could be extensive in vivo.

PMID- 9174283
TI  - Simultaneous determination of cytotoxic (adriamycin, vincristine) and modulator
      of resistance (verapamil, S 9788) drugs in human cells by high-performance liquid
      chromatography and ultraviolet detection.
AB  - Multidrug resistance (MDR), which was described for structurally and
      mechanistically unrelated anticancer agents, was modulated in vitro by a series
      of compounds which were of different chemical origin. In this situation, the
      selection of a correct assay dosage to study the MDR modulation mechanism was a
      problem. We developed a high-performance liquid chomatography (HPLC) method which
      enabled the simultaneous determination of three major cytotoxins (adriamycin,
      daunorubicin, vincristine) and two well-known modulators (S 9788, verapamil).
      This assay was fully validated and was used to follow, for the first time, the
      uptake and accumulation behaviour of adriamycin and S 9788 co-incubated with
      resistant and sensitive cell lines (KB-3-1; KB-A1).

PMID- 9174284
TI  - Direct liquid chromatographic micro-measurement of tamoxifen in plasma of cancer
      patients.
AB  - We describe in this report a sensitive and direct method for the analysis of
      tamoxifen (TAM) in microsamples of plasma. The drug and internal standard
      (quinine bisulfate, I.S.) were separated on a 10-microm particle, 10 cm X 8 mm CN
      cartridge in conjunction with a radial compression system. The mobile phase was a
      mixture of 0.1 M sodium acetate in 0.001 M tetrabutylammonium phosphate solution
      (pH 6) and methanol (30:70, v/v) at a flow-rate of 4 ml/min. After addition of
      I.S. and o-phosphoric acid in acetonitrile (0.6 M) to the plasma (30 microl), the
      mixture was placed in an ultraviolet shortwave transluminator for 2 min prior to
      injection into the chromatograph. The compounds were detected in the effluent
      fluorometrically at excitation and emission wavelengths of 258 and 378 nm,
      respectively. Under these conditions, no interference in the assay from any
      endogenous substance or other concurrently used drugs was observed and the
      retention times of I.S. and TAM were 4.4 and 10.15 min, respectively. The
      concentration of TAM in plasma was linearly (r>0.9983) related to the peak height
      ratio (TAM/I.S.) in the range 0.01-2.0 microg ml(-1) and C.V. at 0.075, 0.4 and
      1.2 microg ml(-1) was < or = 4.96%. We are currently using this assay for
      monitoring TAM in plasma and investigating its pharmacokinetics in cancer
      patients receiving cytotoxic drugs in addition to TAM as a multi-drug resistance
      modifier.

PMID- 9174285
TI  - Investigation of the stereoselective in vitro metabolism of the chiral
      antiasthmatic/antiallergic drug flezelastine by high-performance liquid
      chromatography and capillary zone electrophoresis.
AB  - An achiral HPLC method using a silica gel column as well as two independent
      chiral analytical methods by HPLC and capillary zone electrophoresis (CZE) were
      developed in order to investigate the in vitro metabolism of the racemic
      antiasthmatic/antiallergic drug flezelastine. The chiral HPLC analysis was
      performed on a Chiralpak AD column, which also allowed the simultaneous
      separation of the N-dephenethyl metabolite. The chiral separation by CZE was
      achieved by the addition of beta-cyclodextrin to the run buffer. The
      stereoselectivity of the in vitro biotransformation of flezelastine was
      investigated using liver homogenates of different species. Depending on the
      species, diverse stereoselective aspects were demonstrated. The determination of
      the enantiomeric ratios of flezelastine and of N-dephenethylflezelastine after
      incubations of racemic flezelastine with liver microsomes revealed that porcine
      liver microsomes showed the greatest enantioselectivity of the biotransformation.
      (-)-Flezelastine was preferentially metabolized. After incubations with bovine
      liver microsomes the enantiomer of N-dephenethylflezelastine formed from (+)
      flezelastine dominated. Incubations of the pure enantiomers of flezelastine with
      induced rat liver microsomes resulted in the stereoselective formation of a
      hitherto unknown metabolite, which was only detected in samples of (+)
      flezelastine. Initial structure elucidation of the compound indicated that the
      new metabolite was most likely an aromatically hydroxylated derivative of the N
      dephenethylflezelastine.

PMID- 9174287
TI  - Determination of propofol in rat whole blood and plasma by high-performance
      liquid chromatography.
AB  - A simple, accurate and sensitive high-performance liquid chromatographic method
      was developed for the determination of propofol, an intravenous anaesthetic
      agent, in rat whole blood or plasma samples. The method is based on precipitation
      of the protein in the biological fluid sample and direct injection of the
      supernatant into an HPLC system involving a C18 reversed-phase column using a
      methanol-water (70:30) mobile phase delivered at 1 ml/min. Propofol and the
      internal standard (4-tert.-octylphenol) were quantified using a fluorescence
      detector set at 276 nm (excitation) and 310 nm (emission). The analyte and
      internal standard had retention times of 6.3 and 10.5 min, respectively. The
      limit of quantification for propofol was 50 ng/ml using 100 microl of whole blood
      or plasma sample. Calibration curves were linear (r2=0.99) over a 1-10 microg/ml
      concentration range and intra- and inter-day precision were between 4-11%. The
      assay was applied to the determination of propofol whole blood pharmacokinetics
      and propofol whole blood to plasma distribution ratios in rats.

PMID- 9174286
TI  - Efficient assay for the determination of atenolol in human plasma and urine by
      high-performance liquid chromatography with fluorescence detection.
AB  - An efficient method for the determination of atenolol in human plasma and urine
      was developed and validated. alpha-Hydroxymetoprolol, a compound with a similar
      polarity to atenolol, was used as the internal standard in the present high
      performance liquid chromatographic analysis with fluorescence detection. The
      assay was validated for the concentration range of 2 to 5000 ng/ml in plasma and
      1 to 20 microg/ml in urine. For both plasma and urine, the lower limit of
      detection was 1 ng/ml. The intra-day and inter-day variabilities for plasma
      samples at 40 and 900 ng/ml, and urine samples at 9.5 microg/ml were <3% (n=5).

PMID- 9174288
TI  - What can we learn from provoking ischemia?

PMID- 9174289
TI  - Rapid atrial pacing for detecting provokable demand ischemia in anesthetized
      patients.
AB  - A stress test that can be performed intraoperatively might be valuable for
      cardiac risk stratification in patients needing urgent noncardiac surgery and for
      early evaluation of coronary reserve in patients undergoing aortocoronary bypass
      surgery. Therefore, we evaluated the sensitivity and safety of rapid atrial
      pacing combined with electrocardiography and transesophageal echocardiography for
      inducing and detecting provokable demand ischemia in 20 anesthetized patients
      with multivessel coronary artery disease. Rapid atrial pacing induced ST segment
      changes or new segmental wall motion abnormalities (SWMA), which were defined as
      evidence of induced ischemia in 15 of the 20 patients. Unexpectedly, the new SWMA
      normalized during the first beat after abrupt cessation of pacing in three
      patients who did not show any ST segment changes. Simultaneously, left
      ventricular preload was severely decreased during pacing and recovered to
      baseline immediately when pacing was abruptly discontinued. Rapid atrial pacing
      was safe in all patients, but the target heart rate could not be achieved because
      of heart block or arterial hypotension in 4 of the 20 patients. These findings
      raise the question of whether rapid atrial pacing is the most appropriate
      approach for inducing provokable demand ischemia in anesthetized patients.
      However, its potential usefulness for predicting adverse cardiac outcomes has not
      been evaluated and would require larger studies. In addition, the immediate
      normalization of new SWMA after abrupt cessation of pacing in some patients calls
      into question the validity of new SWMA as evidence of myocardial ischemia when
      left ventricular preload is severely decreased.

PMID- 9174290
TI  - Cognitive dysfunction after ventricular fibrillation during implantable
      cardiovertor/defibrillator procedures is related to duration of the reperfusion
      interval.
AB  - The insertion of implantable cardioverter/defibrillators (ICD) requires induction
      of repeated episodes of ventricular fibrillation (VF). The neuropsychological
      repercussions associated with repeated inducement of hypotension and cerebral
      ischemia are unknown. In this prospective clinical trial, 1 day prior to ICD
      assessment/implantation and 5 days postprocedure, 14 patients underwent
      neurological and cognitive screening. Cognitive dysfunction was defined as
      impaired performance in one of four cognitive domains. Neurological impairment
      was defined as a decrement of 2 or more points from baseline of a total possible
      score of 45 points. Intraoperative hemodynamics, including the reperfusion
      interval (RI; end of preceding fibrillation to beginning of the next), were
      recorded. Patients underwent an average of 12 +/- 6 episodes of VF with average
      duration of mean arterial pressure (MAP) <50 mm Hg for 17 +/- 9 s (range 6-39 s)
      and of MAP <30 mm Hg for 11 +/- 5 s (range 2-22 s). Nine patients, in none of
      whom the predetermined criteria for neurologic impairment was met, demonstrated a
      new subtle neurologic finding postoperatively. Ten of 14 patients met the
      criterion for cognitive dysfunction 5 days postoperatively. The mean RI between
      episodes of VF was significantly different between those patients demonstrating
      cognitive dysfunction and the unimpaired patients (3.1 +/- 0.5 min in the group
      with cognitive dysfunction vs 3.9 +/- 0.8 min in the unimpaired group, P =
      0.027). Five patients without cognitive impairment had longer RI between episodes
      of circulatory arrest than those showing impaired cognition. We conclude that
      cognitive dysfunction can occur after insertion of ICD and is related to the
      duration of RI.

PMID- 9174291
TI  - The effect of hypothermic cardiopulmonary bypass on plasma adrenomedullin in
      adult cardiac surgical patients.
AB  - Cardiopulmonary bypass (CPB) can evoke a systemic inflammatory response, which is
      accompanied by an increase in plasma cytokines that may stimulate the production
      of adrenomedullin (AM), a potent vasodilator peptide. This study was undertaken
      to investigate whether CPB influenced plasma AM concentration in 10 patients
      undergoing cardiac surgical procedures. We found that the plasma AM concentration
      increased significantly after the commencement of CPB, with the greatest increase
      observed at weaning from bypass (P < 0.01). After CPB, plasma AM concentration
      declined but still exceeded baseline significantly 24 h postoperatively. The
      increase in the plasma AM concentration at weaning from CPB correlated
      significantly with aortic cross-clamp time (r = 0.74, P < 0.05). The authors
      conclude that the secretion of AM into circulation is augmented by CPB in
      patients undergoing cardiac surgery, which suggests a possible role of AM in
      cardiovascular regulation during and after surgery with CPB.

PMID- 9174292
TI  - Aprotinin but not tranexamic acid inhibits cytokine-induced inducible nitric
      oxide synthase expression.
AB  - Cell expression of inducible nitric oxide synthase (iNOS) is increased by
      cytokines, which results in high endogenous concentrations of nitric oxide (NO)
      and has been implicated in organ injury, including myocardial reperfusion injury.
      Serine protease inhibitors reduce cytokine-induced iNOS expression. The protease
      inhibitors aprotinin and tranexamic acid, which are used to reduce blood loss
      after cardiac surgery, were evaluated in vitro on cytokine-induced iNOS
      expression and the resulting NO production to demonstrate the relative
      antiinflammatory effects of each drug. A murine bronchial epithelial cell line
      (LA-4) was stimulated with cytomix (tumor necrosis factor alpha, interleukin
      1beta, and gamma-interferon) with or without aprotinin, tranexamic acid, or N
      alpha-tosyl-L-lysine chloromethyl ketone (TLCK; a protease inhibitor). The
      resultant iNOS expression was measured by using Northern blot analysis and cell
      supernatant nitrite concentrations (in aqueous media, NO is oxidized primarily to
      nitrite, NO2-) by chemiluminescence. Nitrite concentrations in the supernatant
      were significantly increased by cytomix, not affected by any concentration of
      tranexamic acid, but significantly (P < 0.05) reduced by aprotinin and TLCK.
      Consistent with the nitrite reduction, aprotinin significantly (P < 0.05) reduced
      cytokine-induced iNOS expression, while tranexamic acid had no effect. Aprotinin
      but not tranexamic acid reduces endogenous cytokine-induced NO production by
      inhibiting iNOS expression. Since increased endogenous NO concentrations
      secondary to iNOS activation have been implicated in organ injury, aprotinin may
      have clinical benefits when compared with tranexamic acid.

PMID- 9174293
TI  - Recommendations for hyperbaric oxygen therapy of cerebral air embolism based on a
      mathematical model of bubble absorption.
AB  - Transcranial doppler studies show that microscopic cerebral artery air emboli
      (CAAE) are present in virtually all patients undergoing cardiac surgery. Massive
      cerebral arterial air embolism is rare. If it occurs, hyperbaric oxygen therapy
      (HBO) is recommended as soon as surgery is completed. We used a mathematical
      model to predict the absorption time of CAAE, assuming that the volumes of
      clinically relevant CAAE vary from 10(-7) to at least 10(-1) mL. Absorption times
      are predicted to be at least 40 h during oxygenation using breathing gas mixtures
      of fraction of inspired oxygen approximately equal to 40%. When CAAE are large
      enough to be detected by computerized tomography, absorption times are calculated
      to be at least 15 h. Decreases in cerebral blood flow caused by the CAAE would
      make the absorption even slower. Our analysis suggests that if the diagnosis of
      massive CAAE is suspected, computerized tomography should be performed, and
      consideration should be given to HBO therapy if the CAAE are large enough to be
      visualized, even if patient transfer to a HBO facility will require several
      hours.

PMID- 9174294
TI  - Preserved sympathetic response to hypotension despite perioperative alpha2
      agonist administration.

PMID- 9174295
TI  - Intrathecal and epidural anesthesia and analgesia for cardiac surgery.

PMID- 9174296
TI  - Tracheal intubation using alfentanil and no muscle relaxant: is the choice of
      hypnotic important?
AB  - Administration of alfentanil followed by propofol intravenously (IV) without
      neuromuscular blockade for induction of anesthesia provides adequate conditions
      for tracheal intubation. Other hypnotic drugs have not been thoroughly
      investigated in this regard. Accordingly, 140 ASA physical status I and II
      premedicated outpatients were randomly assigned to one of seven groups (n =
      20/group). Patients in Groups I-VI received alfentanil 40 microg/kg followed by
      etomidate 0.3 mg/kg, propofol 2 mg/kg, or thiopental 4 mg/kg. One half of these
      patients (Groups II, IV, VI) also received lidocaine 1 mg/kg IV prior to the
      administration of the above drugs. Patients in group VII received d-tubocurarine
      3 mg followed by thiopental 4 mg/kg and succinylcholine 1 mg/kg. Ninety seconds
      after induction, laryngoscopy and endotracheal intubation were attempted and
      graded. Patients in Group V (alfentanil/thiopental) were significantly (P < 0.05)
      more likely to have a clinically unacceptable response to intubation (55%) (e.g.,
      vigorous coughing, purposeful movement, or requirement for succinylcholine to
      complete intubation) compared with patients who received propofol (35%) or
      etomidate (20%). Alfentanil/etomidate yielded intubation conditions comparable to
      those achieved with alfentanil/propofol and d
      tubocurarine/thiopental/succinylcholine. Lidocaine appeared to improve intubating
      conditions, although this improvement did not reach statistical significance. The
      results suggest that healthy, premedicated patients with favorable airway anatomy
      who have received alfentanil 40 microg/kg can be reliably tracheally intubated 90
      s after administration of propofol 2 mg/kg or etomidate 0.3 mg/kg.

PMID- 9174297
TI  - Intrathecal sufentanil for extracorporeal shock wave lithotripsy provides earlier
      discharge of the outpatient than intrathecal lidocaine.
AB  - Many anesthetic techniques are currently used for extracorporeal shock wave
      lithotripsy (ESWL). This randomized, prospective, double-blind study was designed
      to examine postoperative recovery with two anesthetic techniques for unilateral
      ESWL; i.e., intrathecal sufentanil versus intrathecal 5% lidocaine. The incidence
      of adverse effects was also assessed. Twenty-two ASA physical status I-III
      patients, 18-70 yr of age who were scheduled for unilateral ESWL under spinal
      anesthesia were studied. Patients were randomized to receive either intrathecal
      sufentanil 20 microg + saline (n = 11) or intrathecal 5% lidocaine (n = 11) based
      on their height. Both patients and observers were blinded to the treatment
      groups. Patients were assessed for intraoperative and postoperative pain via a 10
      cm verbal analog pain scale (VAPS) (0 = no pain, 10 = extreme pain). Stone sizes,
      number of shock waves, and voltages were also compared. The recovery profile-time
      to ambulate, void, oral intake, and home discharge-was documented. Antiemetic
      requirements in the postanesthesia care unit (PACU) and incidence of
      postoperative nausea and vomiting (PONV), pruritus, and sedation were also
      recorded. This study showed no differences in VAPS between groups at any time in
      the perioperative period. Patients who received intrathecal sufentanil ambulated
      (79 +/- 16 vs 146 +/- 57 min mean +/- SD; P < 0.05), voided (80 +/- 18 vs 152 +/-
      54 min, P < 0.05), and were discharged home (98 +/- 17 vs 166 +/- 50 min, P <
      0.005) significantly sooner than the patients who received intrathecal lidocaine.
      Although 27% (3 of 11) of the patients who received sufentanil reported pruritus,
      respiratory depression was not found. There were no differences in PONV between
      the two groups. Intrathecal sufentanil provided an enhanced recovery profile with
      significantly earlier home discharge when compared with intrathecal lidocaine. In
      conclusion, intrathecal sufentanil is a safe and effective method of anesthesia
      for outpatient unilateral ESWL.

PMID- 9174298
TI  - Glossopharyngeal nerve block for pain relief after pediatric tonsillectomy:
      retrospective analysis and two cases of life-threatening upper airway obstruction
      from an interrupted trial.
AB  - A regional anesthetic technique formerly used in adults for tonsillectomy was
      adapted to provide posttonsillectomy pain relief in children. Injection of 3-10
      mL of 0.25%-0.5% bupivacaine into each lateral pharyngeal space appeared to
      provide good postsurgical analgesia. A retrospective chart review failed to link
      the technique to airway-related complications. A prospective, randomized, double
      blind, placebo-controlled trial comparing the analgesic effectiveness and
      postsurgical complications in patients undergoing tonsillectomy and receiving
      either bupivacaine or placebo was begun after institutional approval and informed
      consent. The study was terminated after eight children had been enrolled because
      two of four children receiving bupivacaine developed severe upper airway
      obstruction (UAO) after extubation of the trachea. We conclude that the volume
      and concentration of bupivacaine were sufficient to block the vagus nerves
      proximal to the take off of the recurrent laryngeal nerves and/or the hypoglossal
      nerves, resulting in severe UAO. The short distance between the hyoid and jugular
      foramen would predispose children and adults with a short neck to the development
      of this complication. In conclusion, bilateral local anesthetic injection into
      the lateral pharyngeal space may result in severe UAO and loss of protective
      reflexes.

PMID- 9174299
TI  - Nicardipine versus nitroprusside for controlled hypotension during spinal surgery
      in adolescents.
AB  - Nicardipine or nitroprusside was used to induce controlled hypotension in healthy
      adolescents with idiopathic scoliosis undergoing spinal fusion. Twenty patients
      were randomly assigned to the nitroprusside (N) or nicardipine (C) group. All
      patients received a standardized anesthetic. A target mean arterial blood
      pressure (MAP) of 60 mm Hg was achieved by varying the vasoactive infusions only.
      Moderate hemodilution (PCV = 25) and intraoperative blood salvage were used in
      all cases. Hemodynamic variables, blood loss, occurrence of reflex tachycardia,
      and reversibility of the hypotensive state were compared between the two groups.
      Significant differences were observed between the two groups in the amount of
      blood loss and reversibility of the hypotensive state. Group C had less blood
      loss (761 +/- 199 mL) than Group N (1297.5 +/- 264, P < or = .05). Time to
      restoration of baseline MAP was longer with Group C (26.8 +/- 4.0 min) than Group
      N (7.3 +/- 1.1 min, P < or = 0.001). Both drugs rapidly achieved a stable,
      controlled hypotensive state and an acceptable operating field. There was no
      statistically significant difference between groups with respect to the amount of
      crystalloid administered or urine output. These results suggest that nicardipine
      is a safe, effective drug for controlled hypotension in this population and that
      it may offer the significant advantage of reduced blood loss in these patients.

PMID- 9174300
TI  - Epidural abscess in a one-year-old boy after continuous epidural analgesia.

PMID- 9174301
TI  - Skin abscess with lumbar epidural catheterization in infants: is it dangerous?
      Report of two cases.

PMID- 9174302
TI  - Dynamic ventilatory characteristics during weaning in postoperative critically
      ill patients.
AB  - Postoperative patients occasionally require more than 48 h of mechanical
      ventilation. This study examined whether there were distinct differences in
      dynamic respiratory variables between patients who successfully weaned from
      mechanical ventilation and those who failed. Forty general and thoracic surgery
      patients underwent a standardized weaning sequence: 25 min of synchronous
      intermittent mandatory ventilation (SIMV) at 8 bpm plus 5 cm H2O pressure support
      ventilation (PSV), then SIMV at 4 bpm plus 5 cm H2O PSV, followed by continuous
      positive airway pressure (CPAP) plus 5 cm H2O PSV and, finally, CPAP without PSV.
      Twenty-eight patients successfully weaned and 12 failed. During SIMV at 4 bpm
      plus 5 cm H2O PSV, the spontaneous respiratory rate to spontaneous tidal volume
      ratio (sRR/sV(T)) and total and spontaneous respiratory rates were higher (P <
      0.01) in the failure group. sRR/sV(T) values (threshold 65 bpm/L, sensitivity
      1.00, specificity 0.82) and sRR values (threshold 12 bpm, sensitivity 0.95,
      specificity 0.84) were distinctive. During CPAP plus 5 cm H2O of PSV, respiratory
      rate, minute ventilation, patient work of breathing, and P0.1 were higher (P <
      0.01) in those who failed. P0.1 (threshold 4.5 cm H2O, sensitivity 1.00,
      specificity 1.00), patient work of breathing (threshold 1.3 J/L, sensitivity
      0.92, and specificity 0.98), and the sRR/sV(T) ratio (threshold 65 bpm/L,
      sensitivity 0.90, specificity 0.80) were distinctive. Most unique was the
      analysis of spontaneous breaths during low SIMV rates. This appears to permit an
      early determination of whether weaning would succeed.

PMID- 9174303
TI  - Determination of the dose-response relationship for intrathecal sufentanil in
      laboring patients.
AB  - Multiple studies have investigated the efficacy of intrathecal opioids,
      particularly sufentanil, in laboring parturients. However, until the important
      pharmacological indices of the 50% and 95% effective doses (ED50 and ED95,
      respectively) are defined, reliable comparative studies among drugs at equipotent
      doses cannot be performed. This study was performed to establish the dose
      response relationship of intrathecal sufentanil analgesia in labor. Sixty
      parturients presenting in active labor received intrathecal sufentanil 2.5 (n =
      10), 5.0 (n = 10), 7.5 (n = 10), 10.0 (n = 10), 12.5 (n = 10), or 15.0 (n = 10)
      microg in a blind, randomized fashion. Patient 100-mm visual analog pain scale
      (VAS) scores, fetal heart rate (FHR), blood pressure, and heart rate were
      recorded at 0, 1, 5, 10, 15, 20, 25, and 30 min after administration of
      sufentanil and then again when the patient requested additional analgesia.
      Absolute VAS < or =25 mm was considered an analgesic success. Percent responders
      was used to construct a dose-response curve and calculate ED50 and ED95. The ED50
      and ED95 for intrathecal sufentanil in laboring parturients were 2.6 (1.8-3.2,
      95% confidence interval) and 8.9 (7.5-11.5) microg, respectively. There was a
      trend toward increasing analgesic duration with increasing sufentanil dose. The
      maternal side effect profile was not different among groups. FHR did not
      appreciably change for any group or individual studied. Assisted delivery and
      cesarean section rates were similar for all groups. Intrathecal sufentanil
      provides rapid onset of analgesia for labor. The ED50 and ED95 values established
      in this study should help to provide benchmarks both for the safe clinical use of
      intrathecal sufentanil for labor and for future comparison studies with other
      intrathecal analgesic techniques.

PMID- 9174304
TI  - The placental transfer of sufentanil: effects of fetal pH, protein binding, and
      sufentanil concentration.
AB  - This study investigated factors that influence the placental transfer of
      sufentanil using the dual-perfused, single-cotyledon human placental model.
      Placentas were collected from healthy women. Experiments were designed to
      elucidate the effects of maternal protein binding, changing maternal sufentanil
      concentration (1, 10, 20, and 100 ng/mL) and decreasing fetal pH (fetal acidemia
      7.2, 7.0, 6.8) on the placental transfer of sufentanil. Sufentanil crossed the
      placenta rapidly at a rate two-thirds that of the transfer marker, antipyrine.
      Sufentanil transfer increased linearly with the maternal concentration (r =
      0.999). Sufentanil/antipyrine maternal to fetal (M-->F) transfer ratios were
      significantly reduced (0.66 +/- 0.05 vs 0.40 +/- 0.04, P < 0.05) when fresh
      frozen plasma was added to the maternal circuit to enhance protein binding. Fetal
      pH and sufentanil transfer were related because sufentanil M-->F clearance
      increased significantly as the fetal pH decreased (r = 0.973, P < 0.05).
      Sufentanil appears to cross the placenta by passive diffusion but is modulated by
      the degree of maternal protein binding. Sufentanil M-->F transfer is enhanced by
      fetal acidemia.

PMID- 9174305
TI  - Intrathecal neostigmine for post-cesarean section analgesia: dose response.
AB  - Intrathecal (IT) neostigmine produces analgesia in animals and humans and
      enhances systemic opioid analgesia. To examine the safety of IT neostigmine for
      eventual use in obstetrics, we studied 24 healthy, term pregnant patients
      scheduled to receive elective cesarean section using a combined spinal-epidural
      anesthetic. Using an open-label, dose-ranging design, patients received either IT
      placebo or neostigmine 10, 30, or 100 microg in a 1-mL solution of 5% glucose in
      normal saline followed in 15 min by 2% epidural lidocaine for cesarean section.
      Neostigmine did not affect fetal heart rate tracings or Apgar scores. The women
      received patient-controlled analgesia intravenous morphine postoperatively.
      Compared with the glucose control, neostigmine produced a dose-independent
      reduction in postoperative morphine use. Cumulative average 24-h morphine use was
      82 +/- 7 mg for women receiving IT placebo and 50 +/- 8 mg for women receiving IT
      neostigmine (P < 0.003). Hourly morphine use was significantly reduced in the
      neostigmine groups for 10 h postoperatively. These data indicate that IT
      neostigmine can produce 10 h of post-cesarean section analgesia without adverse
      fetal effects and support cautious further prospective study.

PMID- 9174306
TI  - A comparison of multiport and uniport epidural catheters in laboring patients.
AB  - The relative incidence of technical difficulties associated with multiport (three
      lateral ports) and uniport (single distal port) epidural catheters remains
      controversial. As part of a continuing institutional evaluation of epidural
      catheter insertion, 500 parturients were randomized to have either a multiport or
      a uniport epidural catheter inserted 6 cm into the epidural space. Multiport
      epidural catheters were associated with inadequate analgesia less often and
      required manipulation less often than uniport epidural catheters. The incidences
      of intravenous cannulation, subsequent catheter dislodgement, and catheter
      replacement were similar for each catheter type. No multiport epidural catheter
      was associated with multicompartment placement. We conclude that multiport
      epidural catheters are preferable for use in laboring patients since they reduce
      the incidence of inadequate epidural analgesia.

PMID- 9174307
TI  - Propofol sedation during awake craniotomy for seizures: electrocorticographic and
      epileptogenic effects.
AB  - This prospective study evaluated the effects of propofol sedation on the
      incidence of intraoperative seizures and the adequacy of electrocorticographic
      (ECoG) recordings during awake craniotomy performed for the management of
      refractory epilepsy. Thirty patients scheduled for temporal or frontal lobectomy
      for epilepsy under bupivacaine scalp block were randomized to receive patient
      controlled propofol sedation (PCS) combined with a basal infusion of propofol (n
      = 15) or neurolept analgesia using an initial bolus dose of fentanyl (0.7
      microg/kg) and droperidol (0.04 mg/kg) followed by a fentanyl infusion (n = 15).
      Propofol administration was suspended 15 min before ECoG recording in the PCS
      group. The occurrence of inappropriate intraoperative seizures was noted and,
      based on blind review, the adequacy of ECoG recordings was compared. A higher
      incidence of intraoperative seizures was noted among the neurolept patients (6 vs
      0, P = 0.008). Intraoperatively, ECoG recordings were adequate to proceed with
      resection in both groups. Evidence of low spike activity on ECoG did not
      correlate with the type of sedation administered. Higher frequency background
      ECoG activity was noted among patients who received propofol, but this did not
      interfere with ECoG interpretation. The use of propofol sedation does not appear
      to interfere with ECoG during epilepsy surgery, provided administration is
      suspended at least 15 min before recording.

PMID- 9174308
TI  - Propofol sedation during awake craniotomy for seizures: patient-controlled
      administration versus neurolept analgesia.
AB  - This prospective study evaluated the safety and efficacy of patient-controlled
      sedation (PCS) using propofol during awake seizure surgery performed under
      bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either
      propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept
      analgesia using an initial bolus dose of fentanyl and droperidol followed by a
      fentanyl infusion (n = 17). Both groups received supplemental fentanyl and
      dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were
      made between groups for sedation, memory, and cognitive function, patient
      satisfaction, and incidence of complications. Levels of intraoperative sedation
      and patient satisfaction were similar between groups. Memory and cognitive
      function were well preserved in both groups. The incidence of transient episodes
      of ventilatory rate depression (<8 bpm) was more frequent among the propofol
      patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid.
      Intraoperative seizures were more common among the neurolept patients (7 vs 0, P
      = 0.002). PCS using propofol represents an effective alternative to neurolept
      analgesia during awake seizure surgery performed in a monitored care environment.

PMID- 9174309
TI  - The effect of skull-pin insertion on cerebrospinal fluid pressure and cerebral
      perfusion pressure: influence of sufentanil and fentanyl.
AB  - This randomized prospective study measured the effects of an intravenous opioid
      bolus on cerebrospinal fluid pressure (CSFP), mean arterial pressure (MAP), and
      cerebral perfusion pressure (CPP) during skull-pin insertion. Twenty-two adult
      patients scheduled for elective craniotomy for supratentorial lesions were
      studied. Outcome variables were MAP, heart rate (HR), and lumbar CSFP. The
      standardized anesthetic regimen included fentanyl (2 microg/kg), thiopental (5-7
      mg/kg), lidocaine (1.5 mg/kg), isoflurane (0.3-0.7 minimum alveolar anesthetic
      concentration), and vecuronium (0.1 mg/kg). During stable anesthesia, sufentanil
      (0.8 microg/kg) or fentanyl (4.5 microg/kg) was given as a bolus before skull-pin
      insertion. The hemodynamic effects of the opioid injection were modified with
      phenylephrine and/or atropine when indicated. CSFP remained unchanged in both
      treatment groups. MAP and CPP increased approximately 10 mm Hg after skull-pin
      insertion (P<0.001). In the sufentanil group, HR decreased approximately 10 bpm
      after opioid injection and remained decreased throughout the study. In fentanyl
      treated patients, HR decreased 8 bpm after opioid injection but returned to
      preopioid rates after skull-pin insertion. In conclusion, in anesthetized
      patients, an intravenous bolus of fentanyl or sufentanil prior to skull-pin
      insertion results in stable values of CSFP, CPP, BP, and HR when the hemodynamic
      effects of the opioid are modified with phenylephrine and atropine.

PMID- 9174310
TI  - Cerebral hemoglobin and optical pathlength influence near-infrared spectroscopy
      measurement of cerebral oxygen saturation.
AB  - Near-infrared spectroscopy (NIRS) is a noninvasive optical technique to monitor
      cerebral oxygen saturation at the bedside. Despite its applicability, NIRS has
      had limited clinical use because of concerns about accuracy, noted by
      intersubject variability in slope and intercept of the line between NIRS- and
      weighted-average arterial-cerebrovenous saturation (SMO2). This study evaluated
      transcranial optical pathlength and cerebral hemoglobin concentration as sources
      for this intersubject variability. Experiments were performed in an in vitro
      brain model and in piglets. Optical pathlength and cerebral hemoglobin
      concentration were measured by time-resolved spectroscopy (TRS). NIRS and TRS
      were recorded in the model, as perfusate blood saturation was varied (0%-100%) at
      several hemoglobin concentrations, and in piglets, as SMO2 was varied (15%-90%)
      before and after hemodilution. In the model, hemoglobin concentration
      significantly altered the NIRS versus blood saturation line slope and intercept,
      as well as optical pathlength. In piglets (before hemodilution), there was
      significant intersubject variability in NIRS versus SMO2 line slope (0.73-1.4)
      and intercept (-24 to 36) and in transcranial optical pathlength (13.4-16 cm) and
      cerebral hemoglobin concentration (0.58-1.1 g/dL). By adjusting the NIRS
      algorithm with optical pathlength or cerebral hemoglobin measurements,
      intersubject variability in slope (0.9-1.2) and intercept (-9 to 18) decreased
      significantly. Hemodilution significantly changed NIRS versus SMO2 line slope and
      intercept, as well as transcranial optical pathlength and cerebral hemoglobin
      concentration (before versus after hemodilution: slope 0.9 vs 0.78, intercept 13
      vs 19, pathlength 13.9 vs 15.6 cm, cerebral hemoglobin 0.98 vs 0.73 g/dL). By
      adjusting the NIRS algorithm with the cerebral hemoglobin measurements, slope and
      intercept remained unchanged by hemodilution. These data indicate that
      intersubject variability in NIRS originates, in part, from biologic variations in
      transcranial optical pathlength and cerebral hemoglobin concentration.
      Instruments to account for these factors may improve NIRS cerebral oxygen
      saturation measurements.

PMID- 9174311
TI  - Suprascapular nerve block for postoperative pain relief in arthroscopic shoulder
      surgery: a new modality?
AB  - Arthroscopic shoulder surgery has a 45% incidence of severe postoperative pain.
      Opiates and interscalene nerve blocks have a high incidence of side effects, and
      intraarticular local anesthetic has been shown to be ineffective when used for
      postoperative pain relief. The suprascapular nerve supplies 70% of the sensory
      nerve supply to the shoulder joint, and local anesthetic block of this nerve is
      effective in certain shoulder pain disorders. To determine the efficacy of a
      suprascapular nerve block, subcutaneous saline was compared with a suprascapular
      nerve block using 10mL of 0.5% bupivacaine with 1:200,000 epinephrine before
      general anesthesia was induced. In the immediate postoperative period, a 51%
      reduction in demand and a 31% reduction in consumption of morphine delivered by a
      patient-controlled analgesic system was demonstrated. There was more than
      fivefold reduction in the incidence of nausea, as well as reduced visual analog
      and verbal pain scores for patients who received a suprascapular nerve block. The
      duration of hospital stay was reduced by 24% in the suprascapular nerve block
      group. A 24-h phone call interview revealed a 40% reduction in analgesic
      consumption and a reduction in verbal pain scores at rest and on abduction. There
      were no complications from the suprascapular nerve block. This study demonstrates
      that a suprascapular nerve block for pain relief in arthroscopic shoulder surgery
      is an effective and safe modality of postoperative pain relief.

PMID- 9174312
TI  - Intraarticular morphine analgesia in chronic pain patients with osteoarthritis.
AB  - Controlled clinical studies have shown that local administration of morphine can
      significantly relieve acute postoperative pain. This analgesic effect is long
      lasting (up to 48 h) and is mediated by peripheral opioid receptors. Experimental
      evidence shows that analgesic effects of peripheral opioids and the density of
      opioid receptors on peripheral sensory nerves increase with the duration of
      painful inflammatory processes. This study examines the analgesic effects of 1 mg
      of morphine injected into the arthritic knee joints of two groups of chronic pain
      patients (n = 23) suffering from osteoarthritis. Using a randomized, double-blind
      cross-over design, patients received either an intraarticular injection of
      morphine and intravenous saline (Group A, n = 13) or an intraarticular injection
      of saline and intravenous morphine (Group B, n = 10) during Phase I. Seven days
      later, patients crossed over to the opposite treatment (Phase II). During Phase
      I, intraarticular morphine resulted in significantly greater pain relief than
      intraarticular saline, and this effect was present at rest as well as during
      movement. The analgesic effect was surprisingly long-lasting and extended into
      Phase II, a carry-over effect that prevented the analysis of Phase II. No side
      effects were reported. The treatment of arthritic pain by peripherally acting
      opioids may be a promising alternative to currently available medications that
      have serious side effects.

PMID- 9174313
TI  - A comparison of propofol with a propofol-ketamine combination for sedation during
      spinal anesthesia.
AB  - Propofol (P) is increasingly used as a sedative during regional anesthesia.
      Providing titratable sedation and rapid recovery, it can compromise hemodynamic
      stability. However, in combination with ketamine (K), it provides stable
      hemodynamics during total intravenous anesthesia, avoiding emergence phenomena.
      We compared the efficacy, respiratory and hemodynamic profiles, and side effects
      of these two sedative regimes in patients undergoing spinal anesthesia. Forty
      patients, ASA physical status I and II, undergoing urologic or orthopedic
      procedures were randomly assigned to one of two groups (n = 20 each). Group 1 (P
      + K) received initial doses of 0.4 mg/kg P, 0.1 mg/kg K, followed by an
      intravenous infusion of 1.2 mg x kg(-1) x h(-1) and 0.3 mg x kg(-1) x h(-1),
      respectively. Group 2 (P) received bolus 0.5 mg/kg and infusion 1.5 mg x kg(-1) x
      h(-1). Subsequent infusion rates were titrated to a predetermined sedation level
      using a 5-point score. Heart rate, arterial pressure, respiratory rate, oxygen
      saturation end-tidal CO2, and oxygen requirements were recorded. Sedation scores
      were similar for both groups. There was no difference in total propofol
      requirements between Group 1 (146 +/- 94 mg) and Group 2 (137 +/- 52 mg) (mean +/
      SD). Mean arterial pressure was significantly higher in the P + K group, e.g.,
      91 mm Hg (86-94) vs 75 mm Hg (69-83) at 30 min (mean +/- SD). Administration of
      vasopressors and fluids as well as recovery and emergence phenomena were similar
      between groups. Although the described additive effect of propofol and ketamine
      was not confirmed, the combination conferred hemodynamic stability during spinal
      anesthesia.

PMID- 9174314
TI  - Postoperative epidural infusion: a randomized, double-blind, dose-finding trial
      of clonidine in combination with bupivacaine and fentanyl.
AB  - The aim of this randomized, double-blind trial of postoperative thoracic epidural
      analgesic infusions was to determine whether clonidine at 10 microg/h (group C10,
      n = 22), 15 microg/h (Group C15, n = 24), or 20 microg/h (Group C20, n = 24)
      improved postoperative analgesia in patients undergoing abdominal gynecologic
      surgery, without side effects or hemodynamic changes, when added to a 5-mL/h
      infusion of 0.125% bupivacaine and fentanyl 2 microg/mL (Group CO, n = 22). The
      24-h study infusion was supplemented, as required, by patient-controlled epidural
      fentanyl. Groups were similar for age, weight, duration, and type of surgery.
      Clonidine produced a dose-dependent improvement in analgesia at rest. Only 20
      microg/h significantly increased the percentage of patients who experienced no
      pain with coughing (relative risk 1.44, 95% confidence interval 1.24-1.94),
      reduced pain scores with coughing (P < 0.05), and significantly lowered
      supplementary fentanyl requirements (P < 0.05). Groups were similar for sedation,
      pruritus, nausea, time to ambulation, and satisfaction with analgesia. Clonidine
      produced a dose-dependent decrease in blood pressure and pulse rate and an
      increase in vasopressor requirement (P < 0.01). Epidural clonidine infused at 20
      microg/h improves analgesia during coughing when combined with epidural
      bupivacaine-fentanyl in patients undergoing lower abdominal surgery but is
      associated with hemodynamic changes and increased vasopressor requirement.

PMID- 9174315
TI  - Comparison of stellate ganglion block with intravascular infusion of
      prostaglandin E1 on brachial artery blood flow in dogs.
AB  - We sought to determine whether sympathetic blockade or infusion of prostaglandin
      E1 (PGE1) is better for vasodilation. We measured brachial artery blood flow
      (BABF) in 10 mongrel dogs using an ultrasonic time flowmeter to compare the
      effects of stellate ganglion block (SGB) and intravascular infusion of PGE1. The
      experimental protocol was designed as follows: 1) intravenous (IV) infusion of
      PGE1 at a rate of 10 ng x kg(-1) x min(-1) for 10 min, 2) IV infusion of PGE1 at
      a rate of 150 ng x kg(-1) x min(-1) for 10 min, 3) intraarterial infusion of PGE1
      at a rate of 0.1 ng x kg(-1) x min(-1) for 10 min, 4) SGB with 0.5% mepivacaine
      1.0 mL was used as a sympathetic blockade. These procedures were successively
      performed on each dog. Mean arterial pressure (MAP), heart rate (HR), and BABF
      were measured before and after each procedure for 40 min. MAP and HR did not
      change significantly after the procedures. BABF increased significantly after IV
      infusion of PGE1 150 ng x kg(-1) x min(-1), intraarterial infusion of PGE1 and
      SGB, reaching maximums of 157%, 174%, and 171% 10 min after IV infusion of PGE1
      150 ng x kg(-1) x min(-1), intraarterial infusion of PGE1 and SGB compared with
      the prevalues, respectively. These data indicate that sympathetic blockade may
      produce the same vasodilation as IV infusion of PGE1 150 ng x kg(-1) x min(-1)
      and intraarterial infusion of PGE1 0.1 ng x kg(-1) x min(-1). Intravascular
      infusion of PGE1 could provide clinically equivalent vasodilation without the
      complications associated with SGB.

PMID- 9174316
TI  - Spinal anesthesia with meperidine. Effects of added alpha-adrenergic agonists:
      epinephrine versus clonidine.
AB  - We determined the effects of intrathecally administered epinephrine and clonidine
      on the duration and quality of a meperidine spinal block. Forty-five patients
      scheduled for orthopedic surgery, divided into three groups, received spinal
      anesthesia with 1 mg/kg 5% meperidine, alone or with 200 microg epinephrine or 2
      microg/kg clonidine. Using a double-blind method, the onset, extension, and
      duration of sensory block (to pinprick) and the duration and degree of motor
      block (Bromage scale) were assessed. Hemodynamic responses, duration of
      postoperative analgesia, degree of sedation, and occurrence of side effects were
      also recorded. The addition of epinephrine to the meperidine solution prolonged
      the sensory block (P<0.01) but did not affect its onset or extent. A similar
      potentiating effect was demonstrated for clonidine (P<0.001). The duration and
      degree of motor block were increased by addition of both epinephrine and
      clonidine. A tendency toward bradycardia and a decrease of mean arterial pressure
      was potentiated by clonidine but not by the epinephrine. Only the addition of
      clonidine prolonged the postoperative analgesia (P<0.001), but was associated
      with an increased sedation score. The incidence of other side effects did not
      differ between the groups. We conclude that coadministration of epinephrine or
      clonidine with meperidine enhances the duration and degree of spinal anesthesia
      and that adding clonidine prolongs the duration of postoperative analgesia.

PMID- 9174317
TI  - The effect of intradermal administration of lidocaine and morphine on the
      response to thermal stimulation.
AB  - Opioids appear to exert a peripheral effect by gaining access to peripheral
      opioid receptors. It has been proposed that inflammatory processes and highly
      osmotic substances could alter the perineural barrier, thereby allowing easy
      access to opioid receptors. Although local anesthetics do not have osmotic
      activity, they are highly active on neural tissue and appear to work
      synergistically with opioids when administered for major conduction blockade. We
      therefore evaluated, in a double-blind fashion, the combination of lidocaine plus
      morphine in an attempt to provide a scientific basis for the use of a combination
      of morphine plus local anesthetics in the periphery. Seven thermal stimuli in 2
      degrees C increments (range 40-52 degrees C) were delivered in a random sequence
      by a computer-controlled thermistor to one of three pretreated sites on 10
      volunteers' forearms: reference site (no injection), lidocaine site (0.1-mL
      intradermal injection of lidocaine 0.5%), or lidocaine plus morphine site (0.1 mL
      of 0.5 mg of morphine plus lidocaine 1%). Pain responses to the thermal stimuli
      were rated by the volunteers using the method of magnitude estimation. Pain
      scores indicated that the combination of lidocaine plus morphine was not more
      effective than lidocaine alone in attenuating the heat-induced pain. Twenty and
      120 min after injection, scores at the lidocaine plus morphine site were 37% and
      20% greater than those at the lidocaine site. The addition of morphine to
      lidocaine did not result in an improvement in the analgesic efficacy and actually
      had an antianalgesic effect.

PMID- 9174318
TI  - Propofol anesthesia increases dopamine and serotonin activities at the
      somatosensory cortex in rats: a microdialysis study.
AB  - We sought to estimate the activities of dopamine and serotonin in animals
      receiving propofol anesthesia. The in vivo microdialysis technique was used in
      Sprague-Dawley rats (n = 6) to measure the major metabolites of dopamine and
      serotonin, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (4
      hydroxy-3-methyphenylacetic acid; HVA) and 5-hydroxy indole acetic acid (5-HIAA)
      in the somatosensory cortex. We also measured the levels of propofol in the brain
      and blood by microdialysis sampling in another group of rats (n = 6). During the
      experiment, the rat was infused intravenously (IV) with propofol at a rate of 10
      mg x kg(-1) x h(-1) for 60 min and 60 mg x kg(-1) x h(-1) for 40 min. We found
      that IV infusion of propofol at a rate of 60 mg x kg(-1) x h(-1) significantly
      increased DOPAC, HVA, and 5-HIAA. We also determined that these changes
      correlated well with propofol levels in the brain and blood. We concluded that
      anesthetic doses of propofol increased the functional activities of dopamine and
      serotonin in the cortex. These increases correlate well with propofol levels in
      the cortex and blood.

PMID- 9174319
TI  - Displacement of the double-lumen endobronchial tube can be detected by bronchial
      cuff pressure change.
AB  - We measured the bronchial cuff pressure of left-sided double-lumen endobronchial
      tubes (DLTs) in 54 patients to confirm the effect of DLT displacement on cuff
      pressure. After positioning the cephalad surface of the bronchial cuff of the DLT
      2.5 cm distal to the carina (23 patients in the first part of the study) or just
      below the carina (23 patients in the second part), the cuff was withdrawn in 0.5
      cm steps during right-sided, one-lung ventilation. The bronchial cuff pressure
      was measured, and the capnogram and pressure-volume loop, displayed by a side
      stream spirometer, was evaluated. After positioning the cephalad surface of the
      bronchial cuff just below the carina (eight patients in the third part),
      bronchial cuff pressure was measured while confirming the position of the
      bronchial cuff during the 30 min of the operative procedure. The bronchial cuff
      pressure decreased significantly by 28.4 cm H2O (P < 0.01) and 21.3 cm H2O (P <
      0.01) in the first and second parts, respectively, before the pressure-volume
      loop or the capnogram changed. The bronchial cuff pressure in the third part
      showed no significant change. We conclude that bronchial cuff pressure monitoring
      was very helpful in detecting displacement of the DLT during right-sided, one
      lung ventilation.

PMID- 9174320
TI  - Evaluation of residual neuromuscular block using train-of-four and double burst
      stimulation at the index finger.
AB  - We examined the percentage of tactile detection of fade in response to train-of
      four (TOF), double burst stimulation3,3 (DBS3,3), or DBS3,2 at the index finger
      compared with that at the thumb during continuous infusion of vecuronium. One
      hundred five adult patients were studied. At TOF ratios (T4/T1) of 0.41-0.70,
      fades in response to TOF were more frequently identified by tactile means at the
      index finger than at the thumb (58% vs 26%, P < 0.05). Similarly, at TOF ratios
      of 0.61-0.90, fades in response to DBS3,3 were more frequently detected at the
      index finger than at the thumb (55% vs 15%, P < 0.05), and at TOF ratios of 0.81
      1.00, the percentage of detection of fade in response to DBS3,2 was higher at the
      index finger than at the thumb (72% vs 40%, P < 0.05). In addition, baseline
      displacement of the index finger or thumb during tactile assessment of fade in
      response to neurostimulation was measured videographically. The baseline
      displacement of the index finger was significantly less than that of the thumb (P
      < 0.05). In summary, the percentage of tactile detection of fade in response to
      neurostimulation at the index finger is higher than at the thumb, and the absence
      of fade in response to DBS3,3 at the index finger is a good indicator of adequate
      recovery from neuromuscular block. This is probably because of the smaller
      baseline displacement of the index finger.

PMID- 9174321
TI  - The effects of sevoflurane anesthesia on insulin secretion and glucose metabolism
      in pigs.
AB  - We investigated the effects of two different concentrations of sevoflurane, 0.4
      minimum alveolar anesthetic concentration (MAC) and 1.0 MAC, on insulin secretion
      before, during, and after sevoflurane anesthesia using three successive
      intravenous glucose tolerance tests (IVGTT) in pigs with indwelling catheters. We
      also investigated changes in the levels of plasma glucose, catecholamines
      (epinephrine [E], norepinephrine [NE]), and cortisol (Cor). The pigs were grouped
      as awake, 0.4 MAC, or 1.0 MAC. Sevoflurane decreased the ratio of insulin/glucose
      (INS/GLU) in the basal condition (P < 0.05 awake versus 1.0 MAC) and during IVGTT
      (P < 0.01 awake versus 1.0 MAC and 0.4 MAC). These decreases were quickly
      reversible (control levels were regained within 2 h of the end of anesthesia),
      were probably dose-related, appeared not to be mediated by E, NE, or Cor. In
      addition, the INS/GLU ratio 2.5-4 h after the end of anesthesia was significantly
      higher in the anesthetized groups than in the awake group. We conclude that
      sevoflurane anesthesia has a rapidly reversible inhibitory effect on basal and
      glucose-stimulated insulin secretion, as do other inhaled anesthetics, and might
      induce insulin resistance.

PMID- 9174323
TI  - The effect of xenon on spinal dorsal horn neurons: a comparison with nitrous
      oxide.
AB  - We compared the effects of xenon (Xe) on the spinal cord dorsal horn neurons with
      those of nitrous oxide (N2O) in cats anesthetized with chrolarose and urethane.
      We assessed the potency of both anesthetics by the inhibition of wide dynamic
      range neuron responses evoked by cutaneous noxious (pinch) stimulation to a
      hindpaw. During 70% Xe inhalation, the responses of 7 of 11 neurons to pinch
      stimulation were suppressed. N2O, 70%, suppressed it in 8 of 11 neurons. The
      potency of Xe and N2O was compared in six neurons that were suppressed by both
      anesthetics. After 20 min of Xe inhalation, the response to pinch was suppressed
      to 49.5% +/- 8.2% (mean +/- SE), while N2O, 70% in oxygen, suppressed it to 45.9%
      +/- 7.9%. The difference between N2O and Xe was not significant. We conclude that
      Xe and N2O suppress the spinal cord dorsal horn neurons to a similar degree.

PMID- 9174322
TI  - The effects of halothane pretreatment on manganese influx induced by muscarinic
      stimulation of airway smooth muscle.
AB  - We hypothesized that halothane inhibits contraction of canine airway smooth
      muscle in part by depleting sarcoplasmic reticulum (SR) calcium stores, which
      affects subsequent force and calcium influx. This hypothesis was tested by using
      the rate of quenching of fura-2 fluorescence by manganese (Mn2+) as an index of
      calcium influx. When added 10 min before submaximum muscarinic stimulation (with
      0.3 microM acetylcholine [ACh]), halothane (0.60 +/- 0.04 mM [mean +/- SE])
      reduced subsequent isometric force and intracellular calcium concentration
      ([Ca2+]i) measured 10 min after contraction (to 55%) +/- 5% and 69% +/- 4% of
      control, respectively). The Mn2+ influx measured concurrently was significantly
      increased by halothane (by 57% +/- 22%). Depletion of SR calcium stores by ACh
      prior to contraction also increased Mn2+ influx (by 46% +/- 6%) but did not
      affect developed force or increase [Ca2+]i in response to submaximum muscarinic
      stimulation. Halothane did not affect [Ca2+]i or Mn2+ influx when added prior to
      maximum stimulation with 100 microM ACh but significantly reduced developed
      force. These findings are consistent with the hypothesis that halothane-induced
      SR depletion prior to contraction stimulates subsequent calcium influx, but they
      further suggest that halothane-induced SR depletion itself does not contribute
      significantly to the reduction in contractility produced by halothane in the
      canine airway smooth muscle.

PMID- 9174324
TI  - Plasma concentrations of lidocaine and bupivacaine after cervical plexus block
      for carotid surgery.

PMID- 9174325
TI  - Cardiac dysrhythmias associated with the intravenous administration of
      ondansetron and metoclopramide.

PMID- 9174326
TI  - Cardiac arrest after mesenteric manipulation in a patient undergoing abdominal
      surgery.

PMID- 9174327
TI  - Successful treatment of epidural abscess with a percutaneously introduced 4
      French catheter for drainage.

PMID- 9174328
TI  - Respiratory arrest after spinal anesthesia with lidocaine and fentanyl.

PMID- 9174329
TI  - Gastric foreign body: a potential risk when using transesophageal echo.

PMID- 9174330
TI  - Droperidol and/or ondansetron.

PMID- 9174331
TI  - Postoperative epidural opioid analgesia: what are the choices?

PMID- 9174332
TI  - Avoiding an impairment of factor VIII:C by using hydroxyethyl starch with a low
      in vivo molecular weight.

PMID- 9174333
TI  - The management and treatment of recurrent postoperative laryngospasm.

PMID- 9174334
TI  - Transient radicular irritation: a misnomer?

PMID- 9174335
TI  - Heart rate variability, respiratory sinus arrhythmia, and mathematical modeling
      of acetylcholine pharmacokinetics/pharmacodynamics in sinus node neuroeffector
      junctions.

PMID- 9174336
TI  - Comparison of end-tidal PCO2 and average alveolar expired PCO2 during positive
      end-expiratory pressure.

PMID- 9174337
TI  - Ketamine in porphyria.

PMID- 9174338
TI  - A sitting position without pressure points.

PMID- 9174339
TI  - Juvenile papillomatosis and airway obstruction.

PMID- 9174340
TI  - Evolution of lipidic structures during model membrane fusion and the relation of
      this process to cell membrane fusion.
AB  - The sequence of events involved in poly(ethylene glycol)-mediated fusion of small
      unilamellar vesicles (SUVs) has been studied. Fusion events were monitored using
      light scattering for vesicle aggregation, the fluorescence lifetime of membrane
      probe lipids (DPHpPC and NBD-PS) for membrane mixing, the aqueous fluorescent
      marker (Tb3+/DPA and H+/HPTS) for contents mixing; and quasi-elastic light
      scattering for the change in the size of vesicles. Poly(ethylene glycol) is a
      highly hydrated polymer that can bring vesicle membranes to near molecular
      contact but is unable to induce vesicle fusion without manipulations that reduce
      packing density and encourage molecular motions in the backbone regions of both
      contacting membrane leaflets. Once this condition is achieved, the sequence of
      events involved in vesicle fusion is shown here to be (1) outer leaflet mixing
      accompanied by (2) transient pore formation, both occurring on a time scale of
      approximately 10 s and leading to an initial, reversible intermediate; (3) a 1-3
      min delay leading to formation of a fusion-committed second intermediate; (4)
      inner leaflet mixing on a time scale of ca. 150 s; and (5) contents mixing on a
      time scale of 150-300 s. Inner leaflet mixing, which has never before been shown
      to be distinct from outer leaflet mixing, begins simultaneously with, but is
      completed before, contents mixing. Fusion products, which seem to be large
      vesicles, are estimated to be formed from four to six SUVs. The fusion
      intermediates are shown to have merged outer leaflets and distinct inner leaflets
      prior to formation of fusion pores. Using quasi-elastic light scattering, the
      initial intermediate was shown to revert to SUVs upon removal of PEG, while the
      second intermediate irreversibly continued to a fusion pore in the presence or
      absence of PEG. The sequence of events for this pure lipid bilayer fusion process
      shows remarkable homology to what is known about the sequence of protein-mediated
      cell membrane fusion events, suggesting a commonality between these two
      processes.

PMID- 9174341
TI  - Phosphorylation site-specific inhibition of platelet-derived growth factor beta
      receptor autophosphorylation by the receptor blocking tyrphostin AG1296.
AB  - The mechanism of action of AG1296, a potent and specific inhibitor of the
      platelet-derived growth factor (PDGF) receptor tyrosine kinase [Kovalenko, M.,
      Gazit, A., Bohmer, A., Rorsman, Ch., Ronnstrand, L., Heldin, C.-H., Waltenberger,
      J., Bohmer, F. D., & Levitzki, A. (1994) Cancer Res. 54, 6106-6114] was
      investigated. This quinoxalin-type tyrphostin neither interferes with PDGF-BB
      binding to the PDGF beta-receptor nor has any effect on receptor dimerization.
      Kinetic analysis of the inhibition was carried out using a synthetic peptide
      substrate (KY751) corresponding to the sequence around tyrosine 751
      autophosphorylation site of the PDGF receptor. It revealed purely competitive
      inhibition vis-a-vis ATP, mixed competitive inhibition vis-a-vis the peptide
      substrate for the non-activated receptor, and mixed competitive inhibition vis-a
      vis both substrates for the activated receptor. Thus, the type of inhibition
      apparently changes upon receptor activation, indicating conformational changes at
      the ATP-binding site. The high degree of selectivity for the tyrphostin AG1296
      might result from the complex type of interaction with the active center of the
      receptor as revealed by the kinetic analysis. Dose-response curves for inhibition
      of the phosphorylation of individual autophosphorylation sites of the PDGF beta
      receptor by AG1296 were different, phosphorylation of tyrosine 857 being the most
      susceptible to inhibition. Thus, phosphorylation of tyrosine 857 in the PDGF
      receptor kinase domain seems dispensable for partial kinase activation. The
      findings are discussed in relation to current models of receptor tyrosine kinase
      activation.

PMID- 9174342
TI  - Structure and assembly of the catalytic region of human complement protease C1r:
      a three-dimensional model based on chemical cross-linking and homology modeling.
AB  - C1r is the modular serine protease responsible for autocatalytic activation of
      C1, the first component of the complement classical pathway. Its catalytic region
      is a noncovalent homodimer of two gamma-B monomers, each comprising two
      contiguous complement control protein (CCP) modules, IV and V [also known as
      short consensus repeats (SCRs)], a 15-residue intermediary segment, and the
      serine protease B domain. With a view to gain insight into domain-domain
      interactions within this region, fragment C1r (gamma-B)2, obtained by autolytic
      proteolysis of the active protease, was cross-linked with the water-soluble
      reagent 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. Cross-linked species
      gamma-B intra and gamma-B inter, containing intra- and intermonomer cross-links,
      respectively, were isolated and then fragmented by CNBr cleavage and trypsin
      digestion. N-Terminal sequence and mass spectrometry analyses of the resulting
      cross-linked peptides allowed us to identify one intramonomer cross-link between
      Lys426 of module V and the C-terminal Asp688 of the serine protease B domain and
      one intermonomer cross-link between the N-terminal Gly280 of fragment gamma and
      Glu493 of the B domain. Three-dimensional homology modeling of the CCP modules IV
      and V and of the B domain was also performed. The complementary information
      provided by chemical cross-linking and homology modeling studies was used to
      construct a three-dimensional model of the gamma-B monomer, in which module V
      interacts with the serine protease on the side opposite to both the active site
      and the Arg446-Ile447 activation site. Also, a tentative three-dimensional model
      of the (gamma-B)2 dimer was built, indicating a loose "head to tail" association
      of the monomers, with the active sites facing opposite directions toward the
      outside of the dimer. The latter model is compared with available low-resolution
      structural data, and its functional implications are discussed in terms of the
      conformational changes occurring during C1r activation.

PMID- 9174343
TI  - Peptide ligands of pp60(c-src) SH2 domains: a thermodynamic and structural study.
AB  - Thermodynamic measurements, structural determinations, and molecular computations
      were applied to a series of peptide ligands of the pp60(c-src) SH2 domain in an
      attempt to understand the critical binding determinants for this class of
      molecules. Isothermal titration calorimetry (ITC) measurements were combined with
      structural data derived from X-ray crystallographic studies on 12 peptide-SH2
      domain complexes. The peptide ligands studied fall into two general classes: (1)
      dipeptides of the general framework N-acetylphosphotyrosine (or phosphotyrosine
      replacement)-Glu or methionine (or S-methylcysteine)-X, where X represents a
      hydrophobic amine, and (2) tetra- or pentapeptides of the general framework N
      acetylphosphotyrosine-Glu-Glu-Ile-X, where X represents either Glu, Gln, or NH2.
      Dipeptide analogs which featured X as either hexanolamine or heptanolamine were
      able to pick up new hydrogen bonds involving their hydroxyl groups within a
      predominantly lipophilic surface cavity. However, due to internal strain as well
      as the solvent accessibility of the new hydrogen bonds formed, no net increase in
      binding affinity was observed. Phosphatase-resistant benzylmalonate and
      alpha,alpha-difluorobenzyl phosphonate analogs of phosphotyrosine retained some
      binding affinity for the pp60(c-src) SH2 domain but caused local structural
      perturbations in the phosphotyrosine-binding site. In the case where a reversible
      covalent thiohemiacetal was formed between a formylated phosphotyrosine analog
      and the thiol side chain of Cys-188, deltaS was 25.6 cal/(mol K) lower than for
      the nonformylated phosphotyrosine parent. Normal mode calculations show that the
      dramatic decrease in entropy observed for the covalent thiohemiacetal complex is
      due to the inability of the phosphotyrosine moiety to transform lost rotational
      and translational degrees of freedom into new vibrational modes.

PMID- 9174344
TI  - Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from
      Escherichia coli.
AB  - UDP-galactose 4-epimerase from Escherichia coli catalyzes the interconversion of
      UDP-galactose and UDP-glucose through the transient reduction of the tightly
      bound cofactor NAD+. The enzyme is unique among the NAD+-dependent enzymes in
      that it promotes stereospecific reduction of the cofactor but nonstereospecific
      hydride return during normal catalysis. In addition to hydride transfer, the
      reaction mechanism of epimerase involves two key features: the abstraction of a
      proton from the 4'-hydroxyl group of glucose or galactose by an active site base
      and the rotation of a 4-ketopyranose intermediate in the active site pocket. To
      address the second issue of movement within the active site, the X-ray structures
      of reduced epimerase complexed with UDP-mannose, UDP-4-deoxy-4-fluoro-alpha-D
      galactose, or UDP-4-deoxy-4-fluoro-alpha-D-glucose have been determined and
      refined to 1.65, 1.8, and 1.65 A resolution, respectively. A comparison of these
      models to that of the previously determined epimerase/NADH/UDP-glucose abortive
      complex reveals that the active site accommodates the various sugars by simple
      rearrangements of water molecules rather than by large changes in side chain
      conformations. In fact, the polypeptide chains for all of the epimerase/NADH/UDP
      sugar complexes studied thus far are remarkably similar and can be superimposed
      with root-mean-square deviations of not greater than 0.24 A. The only significant
      differences between the various enzyme/UDP-sugar models occur in two of the
      dihedral angles defining the conformation of the UDP-sugar ligands.

PMID- 9174345
TI  - Structure of carbamoyl phosphate synthetase: a journey of 96 A from substrate to
      product.
AB  - Carbamoyl phosphate synthetase catalyzes the production of carbamoyl phosphate
      from bicarbonate, glutamine, and two molecules of MgATP. As isolated from
      Escherichia coli, the enzyme has a total molecular weight of approximately 160K
      and consists of two polypeptide chains referred to as the large and small
      subunits. Here we describe the X-ray crystal structure of this enzyme determined
      to 2.8 A resolution in the presence of ADP, Mn2+, phosphate, and ornithine. The
      small subunit is distinctly bilobal with the active site residues located in the
      interface formed by the NH2- and COOH-terminal domains. Interestingly, the
      structure of the COOH-terminal half is similar to that observed in the trpG-type
      amidotransferase family. The large subunit can be envisioned as two halves
      referred to as the carboxyphosphate and carbamoyl phosphate synthetic components.
      Each component contains four distinct domains. Strikingly, the two halves of the
      large subunit are related by a nearly exact 2-fold rotational axis, thus
      suggesting that this polypeptide chain evolved from a homodimeric precursor. The
      molecular motifs of the first three domains observed in each synthetic component
      are similar to those observed in biotin carboxylase. A linear distance of
      approximately 80 A separates the binding sites for the hydrolysis of glutamine in
      the small subunit and the ATP-dependent phosphorylations of bicarbonate and
      carbamate in the large subunit. The reactive and unstable enzyme intermediates
      must therefore be sequentially channeled from one active site to the next through
      the interior of the protein.

PMID- 9174347
TI  - Complex of plastocyanin and cytochrome c characterized by NMR chemical shift
      analysis.
AB  - The complexes of horse ferrous and ferric cytochrome c with Cd-substituted pea
      plastocyanin have been characterized by nuclear magnetic resonance, in order to
      determine the binding sites and to study the effects of complex formation.
      Reproducible, small chemical shift changes (0.005-0.05 ppm) were observed for
      protons in both proteins upon formation of a 1:1 complex. The chemical shift
      changes depended on the ratio of free to bound protein, with a binding constant
      of 1.0 +/- 0.5 x 10(5) M(-1), indicating that they were caused by complex
      formation and that free and bound proteins were in fast exchange. Two-dimensional
      spectra of the complex of ferrocytochrome c and plastocyanin were screened
      systematically for chemical shift changes. For about 760 protons, or 70% of the
      assigned protons in the two proteins, the chemical shift in the complex could be
      established. In plastocyanin and cytochrome c 14% and 17% of the protons,
      respectively, showed a significant chemical shift change. These protons form two
      groups. The first consists of a limited number of surface-exposed side-chain
      protons. These map on the so-called east side of plastocyanin and the front side
      of cytochrome c. This group of chemical shift changes is interpreted as
      representing direct effects of binding, and the respective surfaces thus
      represent the binding sites. The second group includes backbone amide protons and
      a few aliphatic and aromatic protons in the hydrophobic core of each protein. The
      chemical shift changes of this group are interpreted as secondary, i.e., caused
      by very small structural changes which are transmitted deep into the core of the
      protein. Ferric cytochrome c caused the same chemical shift effects in
      plastocyanin as the ferrous form; no intermolecular paramagnetic effects were
      observed. The small size of the chemical shifts and the absence of intermolecular
      paramagnetic shifts and NOEs suggest that the complex consists of a dynamic
      ensemble of structures which are in fast exchange, rather than a single static
      complex. This study shows that small, reproducible chemical shifts can be used
      effectively to characterize protein complexes in detail.

PMID- 9174346
TI  - Recognition of the T stem-loop of a pre-tRNA substrate by the ribozyme from
      Bacillus subtilis ribonuclease P.
AB  - The ribozyme from bacterial ribonuclease P (denoted P RNA) specifically
      recognizes the coaxially stacked T stem-loop and the acceptor stem of a tRNA
      substrate. This recognition is mediated primarily through tertiary interactions.
      At least four 2'-OH groups in the T stem-loop region have been implicated as
      direct contacts with Bacillus subtilis P RNA [Pan, T., et al. (1995) Proc. Natl.
      Acad. Sci. U.S.A. 92, 12510]. Effects of six single 2'-OH --> 2'-H substitutions
      and two base mutants of the G19-C56 tertiary interaction in tRNA on substrate
      binding (Kd) and the chemical step of the reaction (k2) have been determined
      using a tRNA(Phe) substrate containing a 2'-deoxy residue at the cleavage site.
      Our results show that at least five functional groups in the T stem-loop of tRNA
      directly participate in P RNA binding. They include the 2'-OH groups of residues
      54, 56, 61, and 62 and possibly the 4-amino group of the conserved C56. The 2'
      OHs of residues 54, 61, and 62 are positioned within the same minor groove due to
      stacking of the reverse Hoogsteen U54-A58 pair on the G53-C61 Watson-Crick pair
      in the T stem. This groove is extended to the 4-amino group of C56 through the
      tertiary structure of tRNA. We use the term "tertiary groove" to describe
      alignment of functional groups through tertiary folding of an RNA. The binding
      also includes the 2'-OH of nucleotide C56 which is not located in this tertiary
      groove. Assuming additivity, these five interactions can contribute 7.4 kcal/mol
      or 10(5)-fold in binding but only -0.5 kcal/mol or approximately 2-fold in
      chemistry at 37 degrees C. The P RNA binding site for the T stem-loop includes at
      least the previously identified A230 as well as the A130 in B. subtilis P RNA.
      The Kd and k2 data from the A130G mutant of B. subtilis P RNA suggest that A130
      may be proximal to residue 56 in tRNA. These results show how the highly
      structured T stem-loop region in a pre-tRNA substrate is bound by the B. subtilis
      P RNA. This is among the first examples of how a nonhelical RNA structure can be
      recognized by another RNA through tertiary interactions.

PMID- 9174348
TI  - Light-induced spectral changes in fully oxidized cytochrome c oxidase in the
      presence of oxygen.
AB  - Illumination of oxidized cytochrome oxidase with low intensity (<2 mW) light
      below 300 nm in the presence of oxygen causes pH-dependent spectral changes in
      the Soret and visible regions. The light-induced difference spectra show a peak
      at 438 nm and a trough at 414 nm in the Soret region and a peak at 606 nm and a
      shoulder at approximately 577 nm in the visible region. The effect was inhibited
      by cyanide, suggesting the involvement of cytochrome a3. The pH dependence
      indicates two titratable groups with pKa values of 6.52 +/- 0.26 and 6.85 +/-
      0.15. The spectral changes are analogous to those occurring upon addition of
      hydrogen peroxide to the fully oxidized enzyme, which results in a mixture of
      species with absorbance maxima at 607 and 580 nm when referenced against the
      oxidized enzyme. Catalase addition affected the initial onset of the spectral
      change and increased the rate at which the reverse reaction occurred upon
      termination of illumination. The data are consistent with a mechanism involving
      light-induced autoreduction of the binuclear center and subsequent O2 binding,
      followed by the release of hydrogen peroxide and the formation of a mixture of
      the 607 nm and 580 nm forms.

PMID- 9174349
TI  - Fast electron transfer from cytochrome c6 and plastocyanin to photosystem I of
      Chlamydomonas reinhardtii requires PsaF.
AB  - To study the function of the PsaF subunit of photosystem I (PSI), the
      interactions between plastocyanin or cytochrome c6 and PSI isolated from wild
      type and a PsaF-deficient mutant of Chlamydomonas reinhardtii have been examined
      using cross-linking techniques and flash absorption spectroscopy. We show that
      efficient electron transfer from both plastocyanin and cytochrome c6 to PSI
      depends on PsaF. A remarkable feature of the PSI complex of C. reinhardtii is
      that both plastocyanin and cytochrome c6 reduce P700+ with first-order kinetics
      and a half-time of 3 micros, which is unique among photosynthetic organisms
      examined.

PMID- 9174350
TI  - Analysis of pH-induced structural changes of the isolated extrinsic 33 kilodalton
      protein of photosystem II.
AB  - Structural properties of the isolated extrinsic regulatory 33 kDa protein of the
      water-oxidizing complex were analyzed at different pH values. It was found that
      (a) titrations of the buffer capacity reveal a characteristic hysteresis effect
      that is unique for the 33 kDa subunit and is not observed for the other extrinsic
      proteins, (b) changes of the emission from the fluorescence probe 1,8-ANS are
      indicative of an increased accessibility of the hydrophobic core of the 33 kDa
      protein to the dye at lower pH, (c) the near-UV circular dichroism spectrum of
      the polypeptide is altered owing to a pH decrease from 6.8 to 3.8 and becomes
      drastically changed at pH 2.8, and (d) the content of secondary structure
      elements remains virtually constant in the range 3.8 < pH < 6.8, with the
      following values gathered from far-UV CD spectra: approximately 8% alpha-helix,
      approximately 33% beta-strand, approximately 15% turns, and approximately 44%
      random coil. Further acidification down to pH 2.8 gives rise to a decreased alpha
      helix and increased beta-strand and random coil content. A theoretical model
      [Ptitsyn, O., & Finkelstein, A. (1983) Biopolymers 2, 15-22] was used to predict
      the probability and location of secondary structure elements within the protein
      sequence. On the basis of these calculations, an extended hydrophobic beta-sheet
      domain could exist in the center of the protein and an alpha-helix in the C
      terminal region. From these data, the 33 kDa protein is inferred to change its
      tertiary structure in vitro upon acidification of the aqueous environment.
      Possible implications of these features are discussed.

PMID- 9174351
TI  - Isothermal titration microcalorimetric studies for the binding of octenoyl-CoA to
      medium chain acyl-CoA dehydrogenase.
AB  - We investigated the binding of octenoyl-CoA to pig kidney medium chain acyl-CoA
      dehydrogenase (MCAD) by isothermal titration microcalorimetry under a variety of
      experimental conditions. At 25 degrees C in 50 mM phosphate buffer at pH 7.6
      (ionic strength of 175 mM), the binding is characterized by the stoichiometry (n)
      of 0.89 mole of octenoyl-CoA/(mole of MCAD subunit), delta G = -8.75 kcal/mol,
      delta H = -10.3 kcal/mol, and delta S = -5.3 cal mol(-1) K(-1), suggesting that
      formation of MCAD-octenoyl-CoA is enthalpically driven. By employing buffers with
      various ionization enthalpies, we discerned that formation of the MCAD-octenoyl
      CoA complex, at pH 7.6, accompanies abstraction (consumption) of 0.52 +/- 0.15
      proton/(MCAD subunit) from the buffer media. We studied the effects of pH, ionic
      strength, and temperature on the thermodynamics of MCAD-octenoyl-CoA interaction.
      Whereas the ionic strength does not significantly influence the above
      interaction, the pH of the buffer media exhibits a pronounced effect. The pH
      dependence of the association constant of MCAD +octenoyl-CoA <==> MCAD-octenoyl
      CoA yields a pKa for the free enzyme of 6.2. Among thermodynamic parameters,
      whereas delta G remains invariant as a function of temperature, delta H and
      deltaS(standard) both decrease with an increase in temperature. At temperatures
      of < 25 degrees C, delta G is dominated by favorable entropic contributions. As
      the temperature increases, the entropic contributions progressively decrease,
      attain a value of zero at 23.8 degrees C, and then becomes unfavorable. During
      this transition, the enthalpic contributions become progressively favorable,
      resulting in an enthalpy-entropy compensation. The temperature dependence of
      delta H yields the heat capacity change (delta Cp(0)) of -0.37 +/- 0.05 kcal mol(
      1) K(-1), attesting to the fact that the binding of octenoyl-CoA to MCAD is
      primarily dominated by the hydrophobic forces. The thermodynamic data presented
      herein are rationalized in light of structural-functional relationships in MCAD
      catalysis.

PMID- 9174352
TI  - Yeast protein farnesyltransferase: a pre-steady-state kinetic analysis.
AB  - Protein farnesyltransferase catalyzes alkylation of the cysteine in a carboxy
      terminal CaaX motif where a is typically an aliphatic amino acid and X is
      alanine, methionine, serine, glutamine, or cysteine by a farnesyl residue. The
      modification enhances the lipophilicity of farnesylated proteins and promotes
      their association with membranes as part of their normal cellular function. Among
      the proteins modified by farnesyl residues is Ras, an important component in the
      signal transduction network for cell division that has been implicated in several
      forms of human cancer. In this paper, we describe isotope trapping, rapid quench,
      and single turnover experiments with the yeast enzyme using farnesyl diphosphate
      and the short peptide RTRCVIA as substrates. The kinetic constants for substrate
      binding, chemistry, and product release were determined from a fit of the
      differential equations describing the minimal catalytic mechanism to the kinetic
      data by numerical integration. Rate constants for chemistry and product release
      were 10.5 and 3.5 s(-1), respectively. The dissociation rate constant (33 s(-1))
      for release of peptide from the ternary enzyme-substrate complex was three times
      larger than the rate constant for chemistry. The enthalpy of reaction, delta Hrxn
      = -17 +/- 1 kcal/mol for farnesylation of cysteine, was measured by
      microcalorimetry. Isotope trapping experiments revealed that the enzyme-farnesyl
      diphosphate complex was efficiently trapped by peptide but that the enzyme
      peptide complex was not trapped by farnesyl diphosphate. These results are
      consistant with an ordered mechanism for formation of a catalytically competent
      ternary enzyme-farnesyl diphosphate-peptide complex.

PMID- 9174353
TI  - Mechanisms of inhibition of amido phosphoribosyltransferase from mouse L1210
      leukemia cells.
AB  - Amido phosphoribosyltransferase (amido PRTase) catalyses the first step of the
      pathway for de novo biosynthesis of purine nucleotides. The enzyme is subject to
      inhibition by purine nucleoside 5'-monophosphates (AMP, IMP, and GMP), by
      dihydrofolate polyglutamates, and by the antifolate piritrexim [Sant, M. E.,
      Lyons, S. D., Phillips, L., & Christopherson, R. I. (1992) J. Biol. Chem. 267,
      11038-11045). Using a coupled radioassay, we have determined the substrate
      dissociation constants as 80.4 +/- 13.2 microM for 5-phosphoribosyl 1
      pyrophosphate (P-Rib-PP) and 421 +/- 193 microM for L-glutamine with P-Rib-PP
      bound first with positive cooperativity for interaction with a second site on the
      catalytically active dimer (interaction factor of 0.247 +/- 0.042). Analysis of
      inhibition patterns for amido PRTase shows that the antifolate piritrexim is a
      noncompetitive inhibitor bound with positive cooperativity at two allosteric
      sites of an inactive dimer with a dissociation constant of 66.0 +/- 17.8 microM
      for interaction with the free enzyme and an interaction factor of 0.187 +/- 0.113
      with P-Rib-PP as the varied substrate. With L-glutamine as the varied substrate,
      a dissociation constant of 62.3 +/- 15.6 microM for interaction with the enzyme-P
      Rib-PP complex and an interaction factor of 0.0958 +/- 0.0585 microM were
      obtained. AMP binds as a competitive inhibitor with respect to P-Rib-PP with a
      dissociation constant of 40.0 +/- 8.1 microM for interaction with the free enzyme
      and as a noncompetitive inhibitor with respect to L-glutamine with a dissociation
      constant of 16.4 +/- 5.2 mM for interaction with the enzyme-P-Rib-PP complex.
      Sucrose density gradient centrifugation of partially purified amido PRTase showed
      three molecular forms of the enzyme: an inactive tetramer (10.2 S) formed in the
      presence of AMP, an active dimer (6.7 S) formed with P-Rib-PP, and an inactive
      dimer (7.2 S) with piritrexim. The latter species may predominate in cells
      containing high levels of dihydrofolate polyglutamates.

PMID- 9174354
TI  - The propeptide of the vitamin K-dependent carboxylase substrate accelerates
      formation of the gamma-glutamyl carbanion intermediate.
AB  - Vitamin K-dependent carboxylase catalyzes the post-translational gamma
      carboxylation of 9-12 glutamyl residues of several blood coagulation proteins.
      Carboxylase purified from Chinese hamster ovary (CHO) cells as a recombinant FLAG
      carboxylase fusion protein [Sugiura, I., et al. (1996) J. Biol. Chem. 271, 17837
      17844] was utilized with pentapeptide substrate FL[3H-R,S]EAL with high specific
      radioactivity to probe the timing of glutamyl Cgamma-3H cleavage relative to
      Cgamma-COO- bond formation by 14CO2 incorporation rates. Studies were conducted
      over a range of NaH14CO3 concentrations to assess uncoupling of gamma-glutamyl
      carbanion formation and over a range of concentrations of ProPT18, the 18-residue
      peptide corresponding to the -18 to -1 propeptide region of prothrombin known to
      affect the catalytic efficiency of carboxylase. At saturation, ProPT18
      accelerates Cgamma-3H cleavage 11-13-fold and Cgamma-14CO2- formation 6-7-fold,
      converting a Cgamma-3H cleavage/Cgamma-14CO2- formation ratio of 1.2-1.4 in the
      absence of ProPT18 to 2.3-2.8 in its presence, a relative increase in and
      uncoupling of Cgamma-3H cleavage from C-C bond formation. When the HCO3-
      concentration was varied, the V/K3H+/V/K14CO2 ratios rose as HCO3- fractional
      saturation dropped to a ratio of 9.3-10.8/l at low bicarbonate, indicating an
      uncoupling of nine out of ten gamma-glutamyl carbanion formations from
      carboxylative capture, consistent with prior reports on microsomal enzyme
      [Larson, A. E., et al. (1981) J. Biol. Chem. 256, 11032-11035]. These results
      with pentapeptide substrate FLEAL validate reversible gamma-glutamyl carbanion
      formation by pure carboxylase and indicate the ProPT18 increase in catalytic
      efficiency is in selective lowering of an energy barrier preceding the gamma
      glutamyl carbanion intermediate.

PMID- 9174355
TI  - Quenching of tryptophan fluorescence by the active-site disulfide bridge in the
      DsbA protein from Escherichia coli.
AB  - The disulfide oxidoreductase DsbA is a strong oxidant of protein thiols and
      required for efficient disulfide bond formation in the bacterial periplasm. The
      enzyme consists of a thioredoxin-like domain and a second, alpha-helical domain
      which is inserted into the thioredoxin motif. Reduction of the active-site
      disulfide in the thioredoxin domain causes a more than 3-fold increase in
      tryptophan fluorescence. However, both tryptophan residues of the protein, W76
      and W126, are not in contact with the disulfide and located in the alpha-helical
      domain. Analysis of the variants W76F and W126F revealed that the fluorescence of
      W126 is fully quenched in every redox state of DsbA. W126 is also a sink for
      nonradiative energy transfer from W76. In oxidized DsbA, W76 is quenched by an
      intramolecular, dynamic quenching process which involves energy transfer from W76
      via F26 to the disulfide. The contributions of the disulfide bridge and the
      tryptophan residues to the near-UV CD spectra were also quantified. Analysis of
      the thermodynamic stabilities of the variants W76F and F26L revealed that the
      interdomain contact between W76 and F26 strongly contributes to the overall
      stability of DsbA, and selectively stabilizes its oxidized form. The DsbA variant
      F26L is the most oxidizing disulfide oxidoreductase known so far.

PMID- 9174356
TI  - Structure-function studies of the brain-type glucose transporter, GLUT3: alanine
      scanning mutagenesis of putative transmembrane helix VIII and an investigation of
      the role of proline residues in transport catalysis.
AB  - The brain-type glucose transporter (GLUT3) is a high-affinity transporter for D
      glucose and D-galactose and is a member of a family of mammalian sugar
      transporters, each of which are proposed to adopt a secondary structure
      containing 12 transmembrane helices. In an effort to understand structure
      function relationships within such transporters, we have employed alanine
      scanning mutagenesis to examine the functional importance of each residue within
      putative transmembrane helix VIII of the human GLUT3 isoform. Each residue in
      this helix was replaced individually with alanine, and the functional properties
      of the mutants were examined by microinjection of in vitro transcribed mRNA into
      Xenopus oocytes. We show that substitution of residues 305, 306, 308-314, and 316
      325 with alanine had minimal effect on the functional activity of the
      transporter, as determined by measurement of the Km for deoxyglucose transport
      and the Ki for maltose. In contrast, Asn-315 > Ala-315 exhibited a significant
      increase in the Km for deoxyglucose independently of any effect on the Ki for
      maltose. This data suggests that, despite the strong sequence conservation in
      this helix among the GLUT family, no individual residue is absolutely required
      for transport catalysis by this isoform. We have also examined the role of
      proline residues in transport catalysis mediated by GLUT3. Substitution of Pro
      203 (helix VI), Pro-206, Pro-209 (cytoplasmic loop between helices VI and VII),
      Pro-381, Pro-383 and Pro-385 (helix X), Pro-399 (intracellular loop between
      helices X and XI), or Pro-451 (in the carboxy terminus, close to the end of helix
      XII) with alanine did not change the Km for deoxyglucose transport for any
      mutant. However, both Pro-381 and Pro-385 when mutated to alanine exhibited a
      reduction in the Ki for cytochalasin B. In addition, the Ki for maltose
      inhibition of deoxyglucose transport was increased for mutants Pro206Ala,
      Pro381Ala, Pro383Ala, and Pro451Ala. These results will be discussed in terms of
      proposed structural models for the transporters.

PMID- 9174357
TI  - Binding of ligand or monoclonal antibody 4B1 induces discrete structural changes
      in the lactose permease of Escherichia coli.
AB  - By using Cys-scanning mutagenesis with site-directed sulfhydryl modification in
      situ [Frillingos, S., & Kaback, H. R. (1996) Biochemistry 35, 3950-3956],
      conformational changes induced by binding of ligand or monoclonal antibody (mAb)
      4B1 in the lactose permease of Escherichia coli were studied. Out of 31 single
      Cys replacement mutants in helices I, V, VII, VIII, X, or XI, 4B1 binding alters
      the reactivity of Val238-->Cys (helix VII), Val331-->Cys (helix X), or single
      Cys355 (helix XI) permease with N-ethylmaleimide (NEM) in right-side-out membrane
      vesicles. In addition, site-directed fluorescence spectroscopy shows that mAb 4B1
      binding causes position 331 (helix X) in the permease to experience a more
      hydrophobic environment. In contrast, ligand binding elicits more widespread
      changes, as evidenced by enhancement of the NEM reactivity of Ala244-->Cys,
      Thr248-->Cys (helix VII), Thr265-->Cys (helix VIII), Val315-->Cys (helix X),
      Gln359-->Cys, or Met362-->Cys (helix XI) permease, none of which are altered by
      4B1 binding. Furthermore, no effect of 4B1 is observed on the reactivity of
      Cys148 (helix V), Val264-->Cys, Gly268-->Cys, or Asn272-->Cys (helix VIII),
      positions which probably make direct contact with substrate. With respect to the
      N-terminal half of the permease, 4B1 binding causes a small increase in the
      reactivity of mutants Pro28-->Cys or Pro31-->Cys (helix I), while ligand binding
      causes much greater increases in reactivity. The findings indicate that 4B1
      binding induces a structural change in the permease that is much less widespread
      than that induced by ligand binding.

PMID- 9174358
TI  - Alpha 2A-adrenergic receptor stimulated calcium release is transduced by Gi
      associated G(beta gamma)-mediated activation of phospholipase C.
AB  - Proposed mechanisms by which alpha 2-adrenergic receptors (alpha 2AR) regulate
      intracellular calcium ([Ca2+]i) include stimulation and inhibition of cell
      surface calcium channels, stimulation of calcium release via receptor coupling to
      Gq with subsequent activation of phospholipase C and release of IP3, or
      stimulation of calcium release via coupling to Gi in an IP3-independent manner.
      These potential mechanisms were explored in cells that expressed alpha(2A)AR
      endogenously (HEL cells), permanently transfected CHO cells, and transiently
      transfected COS-7 cells. Each cell type displayed agonist (UK14304)-dependent
      increases in [Ca2+]i that were blocked by yohimbine, ablated by pertussis toxin,
      and largely unaffected by chelation of extracellular calcium. Furthermore,
      calcium release was associated with IP3 accumulation and was blocked by an
      inhibitor of phospholipase C (PLC). When expressed in CHO cells, a mutated
      alpha(2A)AR which has the amino and carboxyl termini of the third intracellular
      loop substituted with beta 2AR sequence poorly coupled to Gi in adenylyl cyclase
      assays, and likewise displayed virtually no coupling to increased [Ca2+]i. These
      results all point toward a Gi- versus a Gq-mediated coupling pathway triggering
      release of intracellular calcium stores. The possibility that G(beta gamma)
      subunits released from alpha(2A)AR-Gi coupling is the mechanism of PLC activation
      was explored in COS-7 cells by coexpressing alpha(2A)AR with the G(beta gamma)
      inhibitors transducin or a carboxy-terminal portion of the beta AR kinase. Both
      beta gamma inhibitors markedly inhibited alpha(2A)AR modulation of [Ca2+]i while
      not affecting thromboxane A2 receptor mediated stimulation of [Ca2+]i via Gq
      coupling. Thus, alpha(2A)AR couple to calcium release via Gi-associated G(beta
      gamma) subunits. This coupling is present in multiple cell types and should be
      considered a major signal transduction pathway of this receptor.

PMID- 9174359
TI  - Three-dimensional solution structure and stability of phage 434 Cro protein.
AB  - 1H NMR resonances of the phage 434 Cro protein were assigned using standard 2D
      NMR methods, and its solution structure determined using 867 distance constraints
      in distance geometry (DIANA) calculations ultimately refined by restrained
      molecular dynamics (GROMOS). In the 20 best NMR structures, the average pairwise
      backbone and heavy atom RMSDs are 0.63 +/- 0.14 and 1.53 +/- 0.15 A,
      respectively, for the structurally well-defined residues 4-65. Residues 1-3 and
      66-71 at the N- and C-termini are structurally disordered. The region 4-65
      includes five alpha-helices and tight turns which define the hydrophobic core of
      the protein. The backbone and heavy atom RMSDs for residues 4-65 are 0.92 +/-
      0.12 and 1.99 +/- 0.12 A, respectively, for the NMR versus the crystal
      structures, but there are significant differences in the side-chain conformations
      and solvent accessibilities for some core residues. Analytical
      ultracentrifugation experiments confirm that 434 Cro is monomeric even at the
      high NMR concentrations. 434 Cro folding under NMR solution conditions is two
      state as indicated by coincident urea denaturation curves from circular dichroism
      and intrinsic fluorescence measurements. They yield values for 434 Cro stability
      which show good correspondence to the free energy for global unfolding determined
      by NMR hydrogen exchange measurements for the slowest exchanging amide protons.

PMID- 9174360
TI  - Glutathione reductase turned into trypanothione reductase: structural analysis of
      an engineered change in substrate specificity.
AB  - Trypanosoma and Leishmania, pathogens responsible for diseases such as African
      sleeping sickness, Chagas' heart disease, or Oriental sore, are two of the very
      few genera that do not use the ubiquitous glutathione/glutathione reductase
      system to keep a stable cellular redox balance. Instead, they rely on
      trypanothione and trypanothione reductase to protect them from oxidative stress.
      Trypanothione reductase (TR) and the corresponding host enzyme, human red blood
      cell glutathione reductase (GR), belong to the same flavoprotein family. Despite
      their closely related three-dimensional structures and although their natural
      substrates share the common structural glutathione core, the two enzymes are
      mutually exclusive with respect to their disulfide substrates. This makes the
      parasite enzyme a potential target for antitrypanosomal drug design. While a
      large body of structural data on GR complexes is available, information on TR
      ligand interactions is very limited. When the two amino acid changes Ala34Glu and
      Arg37Trp are introduced into human GR, the resulting mutant enzyme (GRTR) prefers
      trypanothione 700-fold over its original substrate, effectively converting a GR
      into a TR [Bradley, M., Bucheler, U. S., & Walsh, C. T. (1991) Biochemistry 30,
      6124-6127]. The crystal structure of GRTR has been determined at 2.3 A resolution
      and refined to a crystallographic R factor of 20.9%. We have taken advantage of
      the ease with which ligand complexes can be produced in GR crystals, a property
      that extends to the isomorphous GRTR crystals, and have produced and analyzed
      crystals of GRTR complexes with glutathione, trypanothione,
      glutathionylspermidine and of a true catalytic intermediate, the mixed disulfide
      between trypanothione and the enzyme. The corresponding molecular structures have
      been characterized at resolutions between 2.3 and 2.8 A with R factors ranging
      from 17.1 to 19.7%. The results indicate that the Ala34Glu mutation causes steric
      hindrance leading to a large displacement of the side chain of Arg347. This
      movement combined with the change in charge introduced by the mutations modifies
      the binding cavity, forcing glutathione to adopt a nonproductive binding mode and
      permitting trypanothione and to a certain degree also the weak substrate
      glutathionylspermidine to assume a productive mode.

PMID- 9174361
TI  - Acid-induced denaturation of myoglobin studied by time-resolved electrospray
      ionization mass spectrometry.
AB  - The acid-induced denaturation of holo-myoglobin (hMb) following a pH-jump from
      6.5 to 3.2 has been studied by electrospray ionization (ESI) mass spectrometry in
      combination with a continuous flow mixing technique (time-resolved ESI MS).
      Different protein conformations are detected by the different charge state
      distributions that they generate during ESI. The changes in intensity of the
      peaks in the mass spectrum as a function of time can be described by two
      exponential lifetimes of 0.38 +/- 0.06 s and 6.1 +/- 0.5 s, respectively. The
      acid-induced denaturation of hMb was also studied in stopped-flow experiments by
      monitoring changes in the Soret absorption. The lifetimes measured by this method
      are in good agreement with those obtained by time-resolved ESI MS. The shorter
      lifetime is associated with the formation of a transient intermediate which shows
      the mass of the intact heme-protein complex but leads to the formation of much
      higher charge states during ESI than native hMb at pH 6.5. This form of hMb has
      an absorption spectrum similar to that of the native protein, indicating a
      relatively unperturbed chromophore environment inside the heme binding pocket.
      The intermediate can thus be characterized as an unfolded form of hMb with
      essentially intact heme-protein interactions. The longer of the two lifetimes is
      associated with the formation of a product which has a blue-shifted absorption
      spectrum with a much lower maximum absorption coefficient than observed for
      native hMb. In the ESI mass spectrum, this product appears as the apoprotein with
      high charge states which indicates the disruption of the native heme-protein
      interactions and a considerable degree of unfolding compared to native apo
      myoglobin. The mechanism of acid-induced denaturation of hMb, therefore, appears
      to follow the sequence (heme-protein)native --> (heme-protein)unfolded --> heme +
      (protein)unfolded.

PMID- 9174362
TI  - 8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the
      wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the
      cystic fibrosis transmembrane conductance regulator.
AB  - Cystic fibrosis is an autosomal recessive disorder affecting chloride transport
      in pancreas, lung, and other tissues, which is caused by mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR). Certain alkyl xanthines such
      as CPX (8-cyclopentyl-1,3-dipropylxanthine) stimulate Cl- efflux from cells
      bearing the delta F508 genotype common to most cases of cystic fibrosis. We have
      hypothesized that the CFTR molecule itself might be the site for CPX action,
      perhaps in the region of the first nucleotide binding fold (NBF-1) domain.
      Therefore, to test this hypothesis directly we have used a rapid membrane
      filtration assay to measure the kinetics of association and dissociation of
      [3H]CPX to both recombinant NBF-1 and recombinant NBF-1 bearing the delta F508
      mutation. We report that [3H]CPX binds with higher affinity to the delta F508-NBF
      1 of CFTR (Kd = 1.0 nM) than to the wild-type NBF-1 of CFTR (Kd = 17.0 nM). These
      Kd values were calculated from direct measurements of the association and
      dissociation rate constants. The rate constants for the dissociation reaction of
      the wild-type NBF-1 and delta F508-NBF-1 of CFTR were not different from each
      other. However, the corresponding rate constants for the association reaction
      were k(+1) (NBF-1) = 4.7 +/- 0.9 x 10(4) M(-1) s(-1) and k(+1) (delta F508-NBF-1)
      = 1.6 +/- 0.3 x 10(5) M(-1) s(-1), respectively. These Kd values were
      corroborated by equilibrium-binding experiments, which gave very similar values.
      We have also measured the relative displacement of various xanthines from both
      wild-type NBF-1 and delta F508-NBF-1, in anticipation that the order of potencies
      for binding might parallel the action of the different xanthines on CF cells. For
      wild-type NBF-1, the rank order was DA-CPX > DAX > CPX > caffeine > adenosine >>
      IBMX > 2-thioCPX. For delta F508-NBF-1, the rank order was DAX > CPX > caffeine >
      DA-CPX > adenosine >> IBMX > 2-thioCPX. These relative potencies show close
      parallels with previously observed relative potencies of these drugs on CF cells,
      and thus lend strong support to the hypothesis that the mechanism of action on CF
      cells may involve direct interaction with the CFTR molecule itself.

PMID- 9174363
TI  - Human cationic amino acid transporters hCAT-1, hCAT-2A, and hCAT-2B: three
      related carriers with distinct transport properties.
AB  - In this study, we aimed at analyzing the human homologues of the murine cationic
      amino acid transporters mCAT-1, mCAT-2A, and mCAT-2B. cDNAs encoding hCAT-1 had
      been previously reported by two independent groups [Albritton, L.M., et al.
      (1993) Genomics 12, 430; Yoshimoto, T., et al. (1991) Virology 185, 10]. We
      isolated cDNAs encoding hCAT-2A and hCAT-2B from a human liver cDNA library and
      from cDNA derived from the human hepatoma cell line HepG2, respectively. Analyses
      of the deduced amino acid sequences of both carriers demonstrated 90.9% identity
      with the respective murine proteins. In their functional domains (42 amino
      acids), both hCAT-2A and hCAT-2B differ only by one residue from the respective
      mouse proteins. Thus, CAT-2 proteins demonstrate a higher interspecies
      conservation than CAT-1 proteins that are overall 86.5% identical between mouse
      and human and differ by seven residues in the functional domain. The high degree
      of sequence conservation was reflected by the functional similarity of the human
      carriers with their mouse homologues. When expressed in Xenopus oocytes, hCAT-1
      and hCAT-2B demonstrated transport properties consistent with y+. Unlike the
      mouse CAT-1 and CAT-2B, whose transport properties could hardly be distinguished,
      the transport properties of the human CAT-1 and CAT-2B isoforms showed clear
      differences: hCAT-1 had a 3-fold higher substrate affinity and was more sensitive
      to trans-stimulation than hCAT-2B. In contrast to the y+ carriers, hCAT-2A
      exhibited a 10-30-fold lower substrate affinity, a greater maximal velocity, and
      was much less sensitive to trans-stimulation at physiological substrate
      concentrations.

PMID- 9174364
TI  - Determinants involved in the affinity of alpha-conotoxins GI and SI for the
      muscle subtype of nicotinic acetylcholine receptors.
AB  - Nicotinic acetylcholine receptors from muscle contain two functionally active and
      pharmacologically distinct acetylcholine-binding sites located at the alpha/gamma
      and alpha/delta subunit interfaces. The alpha-conotoxins are competitive
      antagonists of nicotinic receptors and can be highly site-selective, displaying
      greater than 10,000-fold differences in affinities for the two acetylcholine
      binding sites on a single nicotinic receptor. The higher affinity site for alpha
      conotoxins GI, MI, and SI is the alpha/delta site on mouse muscle-derived BC3H-1
      receptors. However, alpha-conotoxins GI and MI exhibit higher affinity for the
      other site (alpha/gamma site) on nicotinic receptors from Torpedo californica
      electric organ. alpha-Conotoxin SI does not distinguish between the two
      acetylcholine-binding sites on Torpedo receptors. In this study, alpha-conotoxins
      [K10H]SI and [K10N]SI displayed wild-type affinity for the two acetylcholine
      binding sites on BC3H-1 receptors but a 10-20-fold decrease in apparent affinity
      at one of the two acetylcholine-binding sites on Torpedo receptors. alpha
      Conotoxin [P9K]SI displayed a selective and dramatic increase in the apparent
      affinity for the alpha/delta site of BC3H-1 receptors and for the alpha/gamma
      site of Torpedo receptors. alpha-Conotoxin [R9A]GI displayed a reduction in
      affinity for both acetylcholine-binding sites on BC3H-1 receptors, although the
      extent of its selectivity for the alpha/delta site was retained. alpha-Conotoxin
      [R9A]GI also displayed a loss of affinity for the two acetylcholine-binding sites
      on Torpedo receptors, but its site-selectivity was apparently abolished. These
      results indicate that positions 9 and 10 in alpha-conotoxins GI and SI are
      involved in complex species- and subunit-dependent interactions with nicotinic
      receptors.

PMID- 9174365
TI  - Analysis of nucleotide insertion and extension at 8-oxo-7,8-dihydroguanine by
      replicative T7 polymerase exo- and human immunodeficiency virus-1 reverse
      transcriptase using steady-state and pre-steady-state kinetics.
AB  - Pre-steady-state kinetics of incorporation of dCTP and dATP opposite site
      specific 8-oxo-7,8-dihydroguanine (8-oxoGua), in contrast to dCTP insertion
      opposite G, were examined as well as extension beyond the lesion using the
      replicative enzymes bacteriophage polymerase T7 exo- (T7-) and HIV-1 reverse
      transcriptase (RT). These results were compared to previous findings for
      Escherichia coli repair polymerases I (KF-) and II (pol II-) exo- [Lowe, L. G., &
      Guengerich, F. P. (1996) Biochemistry 35, 9840-9849]. HIV-1 RT showed a very high
      preference for insertion of dATP opposite 8-oxoGua, followed by pol II-, T7-, and
      KF-. Steady-state assays showed k(cat) consistently lower than pre-steady-state
      polymerization rates (k(p)) for insertion of dCTP opposite G or 8-oxoGua and
      insertion of dATP opposite 8-oxoGua. Pre-steady-state kinetic curves for the
      addition of dCTP opposite 8-oxoGua or G by KF-, pol II-, and T7- were all
      biphasic, with a rapid initial single-turnover burst followed by a slower
      multiple turnover rate, while addition of dATP opposite 8-oxoGua by these
      polymerases did not display burst kinetics. With HIV-1 RT, addition of dATP
      opposite 8-oxoGua displayed burst kinetics while addition of dCTP did not.
      Analyses of the chemical step by substitution of phosphorothioate analogs for
      normal dNTPs suggest that the chemistry is rate-limiting during addition of dCTP
      and dATP opposite 8-oxoGua by KF-, pol II-, and T7-; HIV- RT did not show a
      chemical rate-limiting step during addition of dATP opposite 8-oxoGua. Kinetic
      assays performed with various dCTP concentrations indicate that dCTP has a higher
      Kd and lower k(p) for incorporation opposite 8-oxoGua compared to G with all four
      enzymes. The K(d,app)dATP values for KF-, pol II-, and T7- incorporation of dATP
      opposite 8-oxoGua, estimated in competition assays, were found to be 3-10-fold
      greater than the K(d)dCTP. Likewise, the K(d,app)dCTP for HIV-1 RT incorporation
      of dCTP opposite 8-oxoGua was found to be 10-fold greater than the K(d)dATP. The
      repair enzymes (KF- and pol II-) efficiently extended the 8-oxoGua x A pair;
      extension of 8-oxoGua x C was severely impaired, whereas the replicative enzymes
      (T7- and HIV-1 RT) extended both pairs, with faster rates for the extension of
      the 8-oxoGua x A pair. On the basis of these findings, the fidelity of all four
      enzymes during replication of 8-oxoGua depends on contributions from the apparent
      Kd, the ease of base pair extension, and either the rate of conformational change
      before chemistry or the rate of bond formation.

PMID- 9174366
TI  - Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by
      bi- and terbenzimidazoles.
AB  - DNA topoisomerase I has been partially purified from Aspergillus nidulans. The
      purified enzyme is most likely the major nuclear DNA topoisomerase I on the basis
      of the following findings. (1) Purified DNA topoisomerase I can relax both
      positively and negatively supercoiled DNA. (2) Neither an energy cofactor nor
      Mg(II) is required for the relaxation or the cleavage reaction of the enzyme. On
      the basis of a phosphate-transfer experiment, the Aspergillus topoisomerase I was
      shown to have a molecular mass (Mr) of 105 kDa. The differential sensitivity of
      the human and Aspergillus topoisomerase I was compared using a number of known
      human DNA topoisomerase I poisons. Like human DNA topoisomerase I, Aspergillus
      topoisomerase I is highly sensitive to the poisoning activity of camptothecin and
      a number of bi- and terbenzimidazoles. However, unlike human topoisomerase I,
      Aspergillus topoisomerase I is completely resistant to monobenzimidazoles,
      protoberberines (e.g. coralyne), and nitidine. Cytotoxicity studies using yeast
      expressing human and yeast topoisomerase I cDNAs have also demonstrated a similar
      differential sensitivity of yeast topoisomerase I to these human topoisomerase I
      poisons. These results together suggest that the nuclear fungal topoisomerase I
      may be sufficiently different from its human counterpart to serve as a molecular
      target for the development of antifungal drugs.

PMID- 9174367
TI  - Isolation of hammerhead ribozymes with altered core sequences by in vitro
      selection.
AB  - The hammerhead ribozyme has an invariant nucleotide sequence in the core region.
      In order to search for alternative sequences which can support the cleavage after
      the triplet GUC, the core region of 10 nucleotides was randomized and subjected
      to in vitro selection by repeated cycles of transcription, reverse transcription,
      and PCR. Active sequences were isolated after each transcription by denaturing
      PAGE, and after nine cycles of selection, two sequences dominated the pool. Both
      sequences conformed broadly to the consensus core region except that in one
      sequence a single A9U mutation was observed while in the other two mutations at
      A9U and U7A were seen. The catalytic efficiencies of these ribozymes were 6.4 and
      14.1 microM(-1) min(-1), respectively, as compared to 163 microM(-1) min(-1) for
      the consensus sequence. Interestingly, the consensus was not found in any of the
      selected sequences. This discrimination against the consensus sequence was
      attributed to the specificity of the enzymes used in the selection procedure.

PMID- 9174368
TI  - The crystal structure of Citrobacter freundii tyrosine phenol-lyase complexed
      with 3-(4'-hydroxyphenyl)propionic acid, together with site-directed mutagenesis
      and kinetic analysis, demonstrates that arginine 381 is required for substrate
      specificity.
AB  - The X-ray structure of tyrosine phenol-lyase (TPL) complexed with a substrate
      analog, 3-(4'-hydroxyphenyl)propionic acid, shows that Arg 381 is located in the
      substrate binding site, with the side-chain NH1 4.1 A from the 4'-OH of the
      analog. The structure has been deduced at 2.5 A resolution using crystals that
      belong to the P2(1)2(1)2 space group with a = 135.07 A, b = 143.91 A, and c =
      59.80 A. To evaluate the role of Arg 381 in TPL catalysis, we prepared mutant
      proteins replacing arginine with alanine (R381A), with isoleucine (R381I), and
      with valine (R381V). The beta-elimination activity of R381A TPL has been reduced
      by 10(-4)-fold compared to wild type, whereas R381I and R381V TPL exhibit no
      detectable beta-elimination activity with L-tyrosine as substrate. However,
      R381A, R381I, and R381V TPL react with S-(o-nitrophenyl)-L-cysteine, beta-chloro
      L-alanine, O-benzoyl-L-serine, and S-methyl-L-cysteine and exhibit k(cat) and
      k(cat)/Km values comparable to those of wild-type TPL. Furthermore, the Ki values
      for competitive inhibition by L-tryptophan and L-phenylalanine are similar for
      wild-type, R381A, and R381I TPL. Rapid-scanning-stopped flow spectroscopic
      analyses also show that wild-type and mutant proteins can bind L-tyrosine and
      form quinonoid complexes with similar rate constants. The binding of 3-(4'
      hydroxyphenyl)propionic acid to wild-type TPL decreases at high pH values with a
      pKa of 8.4 and is thus dependent on an acidic group, possibly Arg404, which forms
      an ion pair with the analog carboxylate, or the pyridoxal 5'-phosphate Schiff
      base. R381A TPL shows only a small decrease in k(cat)/Km for tyrosine at lower
      pH, in contrast to wild-type TPL, which shows two basic pKas with an average
      value of about 7.8. Thus, it is possible that Arg 381 is one of the catalytic
      bases previously observed in the pH dependence of k(cat)/Km of TPL with L
      tyrosine [Kiick, D. M., & Phillips. R. S. (1988) Biochemistry 27, 7333-7338], and
      hence Arg 381 is at least partially responsible for the substrate specificity of
      TPL.

PMID- 9174369
TI  - Can a two-state MWC allosteric model explain hemoglobin kinetics?
AB  - We have analyzed the nanosecond-millisecond kinetics of ligand binding and
      conformational changes in hemoglobin. The kinetics were determined from
      measurements of precise time-resolved optical spectra following nanosecond
      photodissociation of the heme-carbon monoxide complex. To fit the data, it was
      necessary to extend the two-state allosteric model of Monod, Wyman, and Changeux
      (MWC) to include geminate ligand rebinding and nonexponential tertiary relaxation
      within the R quaternary structure. Considerable simplification of the model is
      obtained by using a linear free energy relation for the rates of quaternary
      transitions, and by incorporating concepts from recent studies on the physics of
      geminate rebinding and conformational changes in myoglobin. The model, described
      by 85 coupled differential equations, quantitatively explains a demanding set of
      complex kinetic data. Moreover, with the same set of kinetic parameters it
      simultaneously fits the equilibrium data on ligand binding and the distribution
      of ligation states. The present results, together with those from single-crystal
      oxygen binding studies, indicate that the two-state MWC allosteric model has
      survived its most critical tests.

PMID- 9174370
TI  - Kinetic folding and cis/trans prolyl isomerization of staphylococcal nuclease. A
      study by stopped-flow absorption, stopped-flow circular dichroism, and molecular
      dynamics simulations.
AB  - We studied the urea-induced unfolding transition of staphylococcal nuclease
      (SNase) and its five proline mutants (P47A, P47T, P117G, P47T/P117G, and
      P47A/P117G) [corrected] by peptide and aromatic circular dichroism and aromatic
      absorption spectroscopy at equilibrium and the refolding-unfolding kinetics of
      the proteins by stopped-flow circular dichroism and stopped-flow absorption
      techniques. Recent studies have revealed that the cis/trans isomerizations about
      the Pro47 and Pro117 peptide bonds of SNase occur not only in the unfolded state
      but also in the native state. The mutational effects on the stability and the
      refolding-unfolding kinetics of SNase were, however, remarkably different between
      the two sites. The substitution of Ala or Thr for Pro47 neither changed the
      stability nor affected the refolding-unfolding kinetics of SNase, whereas the
      substitution of Gly for Pro117 increased the protein stability by 1.2 kcal/mol
      (pH 7.0 and 20 degrees C) and affected the kinetics. These results have been
      attributed to the high flexibility of the loop around Pro47, which has been
      revealed by molecular dynamics simulations of native SNase. Under every condition
      studied, cooperative refolding-unfolding kinetics of SNase were observed.
      Refolding of wild-type SNase was represented by two urea concentration-dependent
      fast phases and a urea concentration-independent slow phase. The double mutant
      (P47T/P117G) [corrected] of SNase still showed multiphasic refolding kinetics
      that involved two urea concentration-independent slow phases, suggesting that
      isomerization of proline residues other than Pro47 and Pro117 may occur in the
      unfolded state of the mutant. Two phases were observed in the unfolding of the
      wild-type and mutant proteins that contained Pro117, a fast phase corresponding
      to the unfolding of the trans isomer and a slow phase corresponding to that of
      the cis isomer. On the basis of these results, the folding scheme of SNase is
      discussed.

PMID- 9174371
TI  - Activation volume of DNA duplex formation.
AB  - The denaturation-renaturation thermal hysteresis was used to investigate the
      kinetics of the helix-coil equilibrium of four 22-base pair homopurine
      homopyrimidine duplex oligonucleotides with fractional G x C base pair content
      (f(G x C)) between 0.14 and 0.5. In 20 mM NaCl and 20 mM Tris-HCl at pH 7.0 and
      at hydrostatic pressures up to 200 MPa, a two-state bimolecular reaction
      mechanism adequately described the observed kinetics. At 1 MPa and 47 degrees C,
      the rate constant for helix formation, k1, increased by a factor of 210, and the
      reverse rate constant, k(-1), decreased by a factor of 420 upon increasing f(G x
      C) from 0.14 to 0.5. The activation energies for formation of the duplexes were
      negative and relatively insensitive to f(G x C). The pressure-induced change in
      the rate constants is related to the activation volume of the reaction step.
      Pressure causes k1 to become larger, and the magnitude of the change in k1 with
      pressure increases the lower the f(G x C) value. Thus, when f(G x C) = 0.14, the
      activation volume for forward reaction, delta V++(1), equals -20 mL/mol, while
      when f(G x C) = 0.5, delta V++(1) = -6.7 mL/mol. The rate constant for strand
      separation, k(-1), decreases at high pressure. The activation volume for this
      step, delta V++(1), varies from 17 to 1.6 mL/mol when f(G x C) = 0.14 and 0.5,
      respectively. The delta V for helix formation calculated from the activation
      parameters changed from -23 mL/mol when f(G x C) = 0.14 to -5.8 mL/mol when f(G x
      C) = 0.5. From extrapolation, it is estimated that the molar volume change for
      formation of G x C base pairs in homopurine-homopyrimidine sequences is
      approximately 0 mL/mol. Parameters calculated from kinetics of other two duplex
      molecules, when f(G x C) = 0.23 and 0.32, lie between these extremes.

PMID- 9174372
TI  - Isoforms of rat liver fatty acid binding protein differ in structure and affinity
      for fatty acids and fatty acyl CoAs.
AB  - Although native rat liver fatty acid binding protein (L-FABP) is composed of
      isoforms differing in isoelectric point, their comparative structure and function
      are unknown. These properties of apo- and holo-L-FABP isoforms were resolved by
      circular dichroism, time-resolved fluorescence spectroscopy, and
      binding/displacement of fluorescent ligands. Both apo-isoforms had similar
      hydrodynamic radii of 18.5 A, but apo-isoform I had a greater alpha-helical
      content and exhibited a longer Tyr lifetime, indicative of secondary and tertiary
      structural differences from isoform II. Isoforms I and II both had two fatty acid
      or fatty acyl CoA binding sites. Ligand binding decreased the isoform
      hydrodynamic radii by 3-4 A and increased Tyr rotational motions in a more
      restricted range. Fatty acyl CoAs were more effective than fatty acids in
      altering the isoform structures. Scatchard analysis showed that both isoforms
      bound cis- parinaric acid with high affinity (Kd values 41 and 60 nM,
      respectively) and bound trans-parinaric acid with 2- and 7-fold, respectively,
      higher affinity than for cis-parinaric acid. In contrast, isoform I had higher
      affinity for cis- and trans-parinaroyl CoAs (Kd values of 33 and 14 nM) than did
      isoform II (Kd values of 110 and 97 nM), thereby resulting in biphasic plots of
      parinaroyl-CoA binding to native L-FABP. Finally, displacement studies indicated
      that each isoform displayed distinct specificities for fatty acid/fatty acyl CoA
      chain length and unsaturation. Thus, rat L-FABP isoforms differ markedly in both
      structure and ligand binding function.

PMID- 9174373
TI  - The effects of NMDA on spontaneous motility and its development in chick embryos.
AB  - The effects of acute and chronic systemic application of N-methyl-D-aspartate
      (NMDA) on the spontaneous motor activity, its development and sensitivity to some
      drugs connected with the function of the NMDA-receptor were studied in chick
      embryos aged from 4 to 19 days of incubation. 1. The acute application of NMDA in
      doses from 20 to 50 mg/kg e.w. evoked in 15- and 17-day-old embryos the
      paroxysmal activation of spontaneous motility in chick embryos both normal and
      chronically decapitated (i.e. in spinal preparations). After chronic pre
      treatment by ketamine (7.17 mg/kg e.w./24 h, from day 4 to day 12 or 16 of
      incubation) the activatory effects of acute NMDA application decreased and
      amounted two thirds of the value in control embryos. 2. As a result of damaged
      development of central motor generator the chronic application of NMDA (the
      average dosis of 2.55 +/- 0.25 mg/kg e.w./24 h) from day 4 of incubation to day
      12 or 16 resulted in 17-day-old embryos in reduction of resting spontaneous
      motility on one hand, and in changed reactivity to acute application of NMDA (20
      mg/kg e.w.) and ketamine (12.5 mg/kg e.w.) on the other hand: the activatory
      effect of NMDA was augmented, whereas the inhibitory effect of ketamine was
      diminished. On the contrary the response of spontaneous motility to acute
      application of glycine (100 mg/kg e.w.) and glutamate (15 mg/kg e.w.) remained
      unchanged. 3. Presented results are evaluated as the proof of possible
      participation of the NMDA-ergic mechanism in the genesis of embryonic spontaneous
      motility.

PMID- 9174374
TI  - Nitric oxide and spontaneous motility in chick embryos.
AB  - The effects of direct donors of the nitric oxide molecule on spontaneous motility
      and its development was investigated in chick embryos. The study was carried out
      in embryos of white Leghorns from the day 4 to day 19 of incubation. Following
      direct donors of NO were used: sodium nitroprusside (SNP), hydroxylamine, 1
      nitrosopyrrolidine and L-arginine, the natural precursor for enzymatic production
      of nitric oxide. 1. SNP evoked apparent depression of spontaneous motility as at
      acute application (20 mg/kg e.w.), as at long-lasting continual supply (1.55 +/-
      0.25 mg/kg e.w./24 h) from e.d. 4 to e.d. 8, 12 or 16). The same depressive
      effect was noted both in normal and spinal embryos. The application of K4Fe(CN)6
      pointed out noticeable participation of the cyanide component and perhaps Fe2+ on
      the SNP effects, too. 2. Hydroxylamine (12.5 mg/kg e.w.) and 1-nitrosopyrrolidine
      (90 and 900 mg/kg e.w.) evoked a significant activation of spontaneous motility
      in chick embryos 3. L-arginine (20 mg/kg e.w.) activated spontaneous motility
      from day 11 of incubation. 4. 1-nitrosopyrrolidine changed not only the resting
      spontaneous motility in 17-day-old chick embryos, but it changed also the
      reactivity of the central generator of motility to some neuropharmacological
      drugs: it potentiated the activatory effect of NMDA, fully abolished the
      inhibitory effect of ketamine, was suppressed by inhibitory effect of Mg2+ and
      its activatory effect was significantly reduced by the inhibitory effects of
      glycine and GABA. 5. These results did not exclude the possible participation of
      NO-ergic components in the onset of embryonic spontaneous motility and in the
      NMDA-ergic activation of the central generator of motor behaviour in chick
      embryos.

PMID- 9174375
TI  - The changes of spontaneous motility in chick embryos after blockade of NO
      synthase.
AB  - The consequences of the blockade of NO-synthase (NOS) for the development,
      frequency and reactivity of spontaneous motility were investigated in chick
      embryos aged 4-19 day of incubation. 1. Acute NOS blockade evoked by N-nitro-L
      arginine- methylester (L-NAME) (20 mg/kg egg weight-e.w.) caused on day 17 of
      incubation the short-lasting depression of spontaneous motility to 50% of resting
      motor activity. L-NAME was in spinal embryos without any effect. Chronic
      application of L-NAME (1.70 mg/kg e.w./24 h) from day 4 of incubation led after
      the first 4 days of continual supply to the development of reduced spontaneous
      motility on one hand, on the other hand it changed the efficacy of central
      activatory (NMDA, pentylenetetrazole) and inhibitory drugs (ketamine, glycine). L
      NAME and L-arginine in different mutual combinations manifested in 17-day-old
      embryos their typical effect, though the depressory effect of L-NAME took a
      swifter course than the activatory effect of L-arginine. 2. Aminoguanidine (AmG)
      (9.8 and 20 mg/kg e.w.) evoked from day 17 of incubation the significant biphasic
      change of spontaneous motility only: initial depression was replaced by later
      activation. AmG was in spinal embryos without effect again. Chronic application
      of AmG (5.29 +/- 0.51 mg/kg e.w./24 h) showed in 17-day-old embryos a reduction
      of resting motility dependent on the duration of AmG influence during incubation.
      Another expression was the changed reactivity of spontaneous motility to some
      centrally effective drugs (ketamine, NMDA, D-cycloserine, glycine,
      pentylenetetrazole). 3. 7-nitroindazole (7-NIZ) (15 and 30 mg/kg e.w.) caused the
      significant decrease of spontaneous motility in chick embryos already from day 15
      of incubation; the depression after the lower dosis had an interrupted course,
      whereas after the higher dosis it was a continuous one. 7-NIZ blocked in 17-day
      old embryos the activatory effect of L-arginine, reduced the paroxysmal
      activation of motility evoked by NMDA and blocked the activatory effect of both
      drugs at simultaneous application. 4. The results support the idea that in the
      CNS of chick embryos NO-ergic mechanism connected with spontaneous motility and
      cooperating with NMDA-ergic neuronal activation develops within the last quarter
      of 21-day incubation.

PMID- 9174376
TI  - Carboplatin-induced micronuclei formation in non-neuronal cells of rat foetal
      dorsal root ganglia cultured in vitro and comparison with another anticancer drug
      -cisplatin.
AB  - Carboplatin-induced chromosomal damage was evaluated in two types of non-neuronal
      cells, fibroblasts and Schwann cells, migrating from rat foetal dorsal root
      ganglia (DRG) in explant cultures by quantification of micronuclei (MN).
      Evaluation of granular condensation of nuclear chromatin, another toxicological
      phenomenon, closely related to activation of apoptosis, was performed to compare
      genotoxic and cytotoxic action of the drug. Both changes were dependent upon the
      concentration of the drug as well as on the exposure time. Dose-response curves
      for micronuclei in fibroblasts revealed normal distribution with the maximum at
      100, 25 and 5 mumol/l after 24, 48 and 72 hours treatment of carboplatin,
      respectively. The maximum number of micronuclei in Schwann cells was obtained at
      25, 25 and 12.5 mumol/l at the same exposure time. Micronucleation of fibroblasts
      represented 293, 382 and 376% of control values and in Schwann cells 366, 819 and
      1667%, respectively. These results were compared with the data obtained in our
      previous experiments where identical cell types were influenced by cisplatin. The
      maximal micronucleation in fibroblasts treated with cisplatin reached 208-385% of
      control values at the same intervals. The maximal number of micronuclei in
      Schwann cells was induced by cisplatin at the dosis about 20 times lower compared
      to carboplatin (ranged from 2 to 0.75 mumol/l) and represented 914, 1032, 1693%
      of control values. Our results suggest that Schwann cells are more sensitive to
      platinum drugs than fibroblasts, especially to cis-DDP. Moreover, carboplatin
      revealed delayed toxic effect in comparison with cisplatin. This finding could
      contribute to the explanation of different neurotoxic potential of both
      cytostatics.

PMID- 9174377
TI  - Effects of hemodialysis on bone mineral as followed by using neutron activation
      analysis.
AB  - The purpose of the study was to bring a contribution to the knowledge of
      physiology and pathophysiology of the bone mineral heteroionic exchange with
      respect to sodium ions and metabolic diseases, particularly bone diseases. The
      instrumental neutron activation analysis was employed to follow the ratio of
      contents Na/Ca in bone samples from dialyzed patients. A formerly elaborated
      method for the determination of the Na/Ca ratio in undecalcified bone tissue
      sections obtained from material embedded in polymethylmethacrylate was used. In
      the reference group the Na/Ca ratio was of 0.021 +/- 0.003, that in patients with
      the renal osteopathy was of 0.030 +/- 0.007. Results obtained in patients with
      different types of the renal osteopathy depending on the intensity of the
      impairment were discussed.

PMID- 9174378
TI  - Toxicity of monomers HEMA, DEGMA and AEMA, used in synthesis of hydrogels for
      medical applications.
AB  - Acute toxicity parameters (lethal doses) were evaluated and calculated after i.m.
      and i.p. administration of 2-hydroxyethyl methacrylate (HEMA), 2
      (hydroxyethoxy)ethyl methacrylate (DEGMA) and 2-(acetoxy)ethyl methacrylate
      (AEMA) to rats. Our previous findings were revisited and corrected. Based on
      preceding standardization and physiological values study, some clinical chemical
      and hematological markers of in vivo subacute i.m. toxicity were followed.
      Hematological parameters revealed to be of low sensitivity to the toxic
      influence. Clinical chemical tests suggest the prevalent muscle cell injury.

PMID- 9174379
TI  - Half a century with scientific medical information in Czechoslovakia.
AB  - The author reviews his participation in the development of scientific medical
      information in the former Czechoslovakia, beginning with the classical methods
      using the Universal Decimal Classification, through the development of the method
      of manual peek-a-boo punched cards, till the experimental and routine use of the
      first commercially available National Elliott 8O3B and Minsk-22 computers (Index
      Radiohygienicus with a KWIC index). Simultaneously he founded and managed the
      Information Center for Radiation Protection, and later the Information Center of
      the Institute of Hygiene and Epidemiology. Then he was charged with the
      projection and methodological guidance of the system of libraries and information
      centers in the Czech health institutions. In his theoretical and experimental
      research the author was interested in the feasibility of algorithms for the
      selection of keywords from scientific texts, in the modelling of the
      communication of medical scientific information in Czechoslovak conditions, and
      in extensive statistical studies of the relation between information supply to
      authors and their citation behavior and citedness. Practical measures for
      overcoming information barriers were suggested. All results of these activities
      were published in more than 100 papers and research reports, half of which are
      cited in References.

PMID- 9174380
TI  - Impairment of adenosine-induced dilation of forearm resistance arteries in
      patients with arterial hypertension.
AB  - BACKGROUND: Adenosine is a potent mediator of arteriolar tone in particular
      during ischemia, hypoxia, and exercise. Functional disturbance of this dilatory
      pathway may be highly significant for the pathophysiology and pathogenesis of
      arterial hypertension. PATIENTS AND METHODS: Forearm blood flow (FBF) was
      quantified by venous occlusion plethysmography following intra-arterial infusion
      of adenosine at increasing doses in 13 patients with arterial hypertension (HT)
      and 12 age-matched normotensive controls (NT). Hyperemic peak flow was measured
      following 3 minutes of non-flow ischemia. RESULTS: FBF at rest was comparable in
      both groups and was dose-dependently increased by adenosine in both groups. In
      patients with HT adenosine-induced vasodilation was significantly impaired over
      the entire dose-response curve compared with NT (6.0 mumol/min: 14.5 +/- 1.0
      versus 8.6 +/- 0.9 ml.min-1.100 ml-1 of tissue, p < 0.01). Maximum forearm blood
      flow during reactive hyperemia was also profoundly impaired in the hypertensive
      patients (-38%, p < 0.01). In the overall group of normotensive and hypertensive
      subjects, flow responses to adenosine were i) significantly correlated with peak
      flow (adenosine 2.0 mumol/min: r = 0.79, p < 0.001), and total flow during
      reactive hyperemia and ii) inversely related to the magnitude of arterial blood
      pressure. CONCLUSIONS: The study reported presents first evidence that adenosine
      dependent dilation of forearm resistance arteries is impaired in patients with
      arterial hypertension. This vascular dysfunction is associated with the
      impairment of ischemia-induced reactive hyperemia which in turn may contribute to
      progressive end-organ damage in arterial hypertension.

PMID- 9174381
TI  - Changes of cytokeratin expression in the epidermis with chronic venous
      insufficiency.
AB  - BACKGROUND: A specific, individual pattern of cytokeratins (Cks) is expressed by
      each epithelial cells as part of the cytoskeleton. Cks are established as markers
      of epidermal differentiation. Basal cells are characterized by CK5 and 14
      expression, whereas CK 1, 10 and 11 are typical for the suprabasal compartment of
      normal epidermis. Here, we investigated changes of Pan-CK, CK 10, and CK 14
      expression in the epidermis in various stages of chronic venous insufficiency
      (CVI). PATIENTS AND METHODS: In punch biopsies of 24 patients with chronic venous
      insufficiency and of 6 volunteers with normal skin Cks were detected by indirect
      immunofluorescence using monoclonal antibodies against CK 10, CK 14 and Pan-CK.
      RESULTS: CK 10 and Pan-CK staining intensity increased with the severity of CVI
      changes. Suprabasal cells showed an upregulation of CK 10 and Pan-CK expression
      first in venous eczema. CK 14 expression is under normal condition confined to
      the basal cell layer of the epidermis. However in venous eczema and
      lipodermatosclerosis, CK 14 is detected in the suprabasal epidermal compartment.
      CONCLUSIONS: It is therefore concluded that altered differentiation and
      stratification mechanisms occur in keratinocytes in the epidermis with CVI first
      detectable in the stage of venous eczema. These changes are accompanied by a
      characteristic CK expression pattern.

PMID- 9174382
TI  - Local treatment of venous ulcers with tissue type plasminogen activator
      containing ointment.
AB  - BACKGROUND: The pathogenesis of venous leg ulcers is still not known. One
      hypothesis states that pericapillary fibrin cuffs might play an important role.
      These fibrin cuffs might not be broken down because of an inadequate fibrinolytic
      activity. PATIENTS AND METHODS: To stimulate fibrinolysis, tissue type
      plasminogen activator (t-PA) containing ointment was applied over 12 weeks on
      chronic venous leg ulcers of six patients. Three of the six ulcers healed within
      this period. Biopsy specimens for immunofluorescence studies were taken from the
      ulcer base and margin before and at the end of treatment and, if the ulcer had
      healed, from the healed area. RESULTS: Deposition of pericapillary fibrin was
      seen around the capillaries of all investigated ulcers at the start of the study.
      Pericapillary fibrin was still present with nearly undiminished intensity at the
      end of the study even though 3 of the ulcers healed. CONCLUSION: It is most
      likely that the healing of these ulcers was not improved by the fibrinolytic
      activity of t-PA, but caused by other wound healing properties of t-PA.

PMID- 9174383
TI  - Colour coded duplex sonography in ischemic finger artery disease--a comparison
      with hand arteriography.
AB  - BACKGROUND: A reliable non-invasive diagnostic procedure is desirable to exclude
      arterial pathology in patients with pain in their fingers. PATIENTS AND METHODS:
      The results of colour coded duplex sonography (CCDS) in 450 finger arteries (45
      hands/41 patients) were compared with findings obtained by intra-arterial digital
      subtraction arteriography (i.a.-DSA). The population consisted of symptomatic
      patients with a high risk for finger artery pathologies. RESULTS: Arteriography
      of the hand documented finger artery occlusion in 35.6% of these patients. CCDS
      is capable of detecting pathological alterations in finger arteries with high
      accuracy and can differentiate them from regular arteries. In patients with
      several diseases of the finger arteries, the ultrasound diagnosis concurred with
      arteriography in 93.1% of patent arteries. In patients with occluded arteries the
      accuracy of CCDS was 86.3%. CONCLUSION: When assessing diseases of finger
      arteries non-invasive CCDS should be used routinely before referring the patient
      to arteriography. The latter is only indicated when there is a need to image the
      whole arterial trunk of the upper extremity or the hand, or in case of equivocal
      results of CCDS.

PMID- 9174384
TI  - Mesenteric inflammatory veno-occlusive disease (MIVOD): an emerging and
      unsuspected cause of digestive tract ischemia.
AB  - BACKGROUND: Mesenteric inflammatory veno-occlusive disease (MIVOD) is a new
      clinicopathological entity and an unsuspected cause of digestive tract ischemia
      in the 17 patients reviewed in this article. PATIENTS AND METHODS: Of this
      series, MIVOD occurred twice as often in men as in women, and the age of affected
      patients ranged from 24 to 78 years. Unexplained ischemic bowel disease was the
      most common clinical presentation of MIVOD. All patients required surgical
      exploration and underwent resection of ischemic or gangrenous bowel. None of the
      patients had a known underlying systemic vasculitis, connective tissue disease,
      inflammatory bowel disease, infection, drug allergy, or ingestion of food
      contaminants or toxins. RESULTS: In general, a correct diagnosis of MIVOD is
      possible in virtually all cases only after careful histological examination of
      the resected specimens because the endoscopic biopsy findings may be
      inconclusive. The inflammatory infiltrate of active MIVOD may be lymphocytic,
      necrotizing, granulomatous, or mixed, and thrombosis is almost invariably also
      present. The late changes of MIVOD, concentric or eccentric myointimal
      hyperplasia and occlusive phlebosclerosis, represent organized thrombi.
      CONCLUSION: MIVOD probably occurs more commonly than is generally recognized. To
      a casual observer, the presence of thrombosis may overshadow the inflammatory
      component of a veno-occlusive disease, especially in the absence of arterial
      vasculitis, many cases of MIVOD can conceivably go undiagnosed.

PMID- 9174385
TI  - Whole-blood immunoassay (SimpliRED) versus plasma immunoassay (NycoCard) for the
      diagnosis of clinically suspected deep vein thrombosis.
AB  - BACKGROUND: The level of D-dimer in the blood reflects the level of lysed, cross
      linked fibrin, and is a useful diagnostic marker in patients with clinically
      suspected deep vein thrombosis (DVT). In this study, two assays for the
      measurement of D-dimer levels were compared: the new, whole-blood immunoassay,
      SimpliRED, which can be performed at the patient's bedside in two minutes; and
      the plasma immunoassay, NycoCard. PATIENTS AND METHODS: D-dimer levels were
      determined using these two techniques in 108 patients with clinically suspected
      DVT. To ascertain or rule out the diagnosis of DVT compression ultrasonography
      using a colour coded Duplex instrument was done. 8 doubtful cases were diagnosed
      by ascending phlebography. By these procedures DVT was confirmed in 33 patients
      and ruled out in the remaining 75 cases. RESULTS: The SimpliRED assay exhibited a
      sensitivity of 1.0 (CI 0.89-1.0) and a specificity of 0.75 (CI 0.63-0.84);
      negative predictive value 1.0 (CI 0.94-1.0), positive predictive value 0.63 (CI
      0.49-1.0). By contrast, the NycoCard assay displayed a sensitivity of 0.85 (CI
      0.68-0.95) and a specificity of 0.65 (CI 0.53-0.76); negative predictive value
      0.91 (CI 0.80-0.97), positive predictive value of 0.52 (CI 0.38-0.66).
      CONCLUSION: The results show that the SimpliRED assay is a valuable tool in the
      diagnosis of clinically suspected DVT, especially when laboratory facilities are
      not accessible.

PMID- 9174386
TI  - Gasless videoendoscopic implantation of aortobifemoral vascular prostheses via a
      transperitoneal approach--an animal experiment.
AB  - BACKGROUND: Standard approach for aortobifemoral vascular approach prostheses is
      the transperitoneal approach, following median laparotomy and bilateral inguinal
      incision. The goal of this animal experiment was the development of a new minimal
      invasive surgical technique utilizing a less-traumatic approach for
      aortobifemoral bypass. METHODS: The gasless videoendoscopic implantation of 6 x 6
      mm diameter aortobifemoral-bifurcation prostheses in transperitoneal approach was
      tested at the Surgical Department of the University of Cologne in 10 domestic
      pigs. Gasless videoendoscopic surgery is performed with a laparolift-laparfan
      system. After videoendoscopic implantation of aortobifemoral prostheses, all 9
      animals underwent laparotomy and resection of the aortobifemoral prosthetic
      segment. The quality of the endoscopically sutured aortic end-to-side anastomoses
      was examined under artificial in-vitro circulation of glycerol/ringer-lactate
      solution for evaluation of possible leakage and bursting pressures. Moreover, the
      anastomoses were compared to conventionally sutured end-to-side anastomoses of
      six-hour old porcine abdominal aortas and 6 mm diameter prostheses. The maximum
      bursting pressure of all endoscopically sutured anastomoses averaged 450 mmHg,
      whereby the minimum bursting pressure amounted to 100 mmHg mean pressure.
      RESULTS: Aortobifemoral prostheses were successfully implanted in 9 out of 10
      animals, one animal dying during preparation for the surgery, succumbing to
      massive coronary infarctions. Surgical durations for the transperitoneal approach
      averaged four hours, whereby surgical durations were reduced with increasing
      experience to a minimum of 3 hours 30 minutes. Dissection of the infrarenal aorta
      until occlusion required 35 minutes. Average aortic occlusion duration amounted
      to 1 hour; iliacofemoral occlusion duration amounted to 1 hour for each side. The
      leakage per minute at the beginning achieved a maximum of 80 ml/min and systolic
      pressure values of 350 mmHg in consideration of all flow levels, 60 ml/min for
      systolic pressure values of 200 mmHg and 20 ml/min for systolic pressure values
      of 120 mmHg. The minimum level leakage per minute was less than 10 ml/min for
      systolic pressure values between 120-350 mmHg. CONCLUSION: Gasless
      videoendoscopic implantation of aortobifemoral vascular prostheses in
      transperitoneal approach is practicable in animal experiments. All endoscopically
      sutured aortic endo-side anastomoses were comparable to conventionally sutured
      anastomoses in in-vitro evaluation of bursting pressure and leakage per minute.

PMID- 9174387
TI  - Ultrasound guided compression therapy in 134 patients with iatrogenic pseudo
      aneurysms: advantage of routine duplex ultrasound control of the puncture site
      following transfemoral catheterization.
AB  - BACKGROUND: The following study was designed to evaluate the effectiveness and
      safety of ultrasound guided compression therapy (UGCT) of iatrogenic
      postcatheterization pseudo-aneurysms (PA) on the one hand and to justify the
      usefulness of the routine colour duplex control of the puncture site following
      transfemoral catheterization, on the other hand. MATERIAL AND METHODS: During the
      study period 142 patients with (PA) following transfemoral catheterization were
      identified by means of colour duplex examination Eighty of these 142 patients
      were identified during a routine colour duplex control of the puncture site the
      day after PTA/angiography because of peripheral arterial occlusive disease (PAOD)
      [group A]; the remaining 62 patients with symptomatic groins were referred from
      other departments [group B]. RESULTS: In 8 patients of group B UGCT was
      considered to be contra-indicated, they were primarily treated by surgical repair
      of the PA. A total of 134 patients (group A 80 patients, group B 54 patients)
      underwent an UGCT. In total the success rate of UGCT was in group A 100% and in
      group B 78%. 12/54 patients (all group B) with failure of UGCT underwent a
      secondary surgical repair of the PA. Within group B there was a negative
      correlation between delay of diagnosis/UGCT and success (p < 0.04), whereas the
      size of the sheath did not influence the outcome of the UGCT (p = 0.3).
      CONCLUSION: Our study confirms the effectiveness and safety of UGCT. Routine
      colour duplex control of the puncture site the day following the removal of the
      sheath after percutaneous catheterization and UGCT of PAs without delay can
      increase the success rate of UGCT and minimize the need for surgical repair of
      PAs.

PMID- 9174388
TI  - Effects of adjuvant PGE1 therapy following profundaplasty in patients with severe
      limb ischaemia. Early and long-term results.
AB  - BACKGROUND: In patients with peripheral arterial occlusive disease (PAOD) of
      stage III/IV and three-level occlusion, the outcome of vascular surgery is still
      unsatisfactory. Therefore, the aim of our study was to determine both the short
      term results and the long-term outcome, in terms of limb salvage and patient
      survival, of adjuvant intravenous prostaglandin E1 (PGE1) treatment in patients
      undergoing profundaplasty. PATIENTS AND METHODS: A prospective randomized placebo
      controlled study was conducted in 83 patients with PAOD of the lower extremities
      (stage III or IV according to Fontaine). Profundaplasty was carried out in all
      patients. Starting on the day of surgery and continuing for three weeks, patients
      of the PGE1 group (n = 42) received twice daily a 2-hour intravenous infusion of
      60 micrograms PGE1 in 250 ml of physiological saline. Patients of the control
      group (n = 41) were given only saline by the same regimen. Following discharge
      from hospital, patients were re-examined after 6 weeks and subsequently every 6
      months for a period of up to 5 years. RESULTS: Short-term results: In the PGE1
      group, rest pain disappeared and necrotic lesions healed in a significantly
      larger proportion of patients as compared with the control group (62% vs 37%; p =
      0.05). Moreover, the number of minor amputations, such as toe and forefoot
      amputations, was significantly smaller in patients treated with PGE1 (7 vs. 19; p
      < 0.001). Long-term results: By the end of the 5-year follow-up period, a
      significantly larger percentage of patients was still alive in the PGE1 group as
      compared with control (55% vs. 34%; p = 0.046). Moreover, significantly less
      major amputations became necessary during follow-up in the PGE1 group (8 vs. 16;
      p = 0.0088). CONCLUSIONS: In patients undergoing profundaplasty because of severe
      limb ischemia due to three-level occlusion, adjuvant intravenous 3-week treatment
      with PGE1 substantially improves not only the short-term results, but also the
      long-term outcome after five years in terms of patient survival and limb salvage.

PMID- 9174389
TI  - Improvement in the quality of life after i.v. PGE1 therapy for intermittent
      claudication.
AB  - BACKGROUND: Increasingly and justifiably, clinical studies are now being expected
      to investigate the influence of therapeutic measures also on the quality of life
      of the patient. PATIENTS AND METHODS: Since no data on the variability of changes
      in the quality of life of the patient following PGE1 treatment are so far
      available, the initial investigation was designed as an uncontrolled pilot study.
      104 patients (median age 64.5 years) with a maximum of walking distance on the
      treadmill (3 km/12%) of 50-250 m were included and given a daily intravenous
      infusion of 60 micrograms PGE1 (Prostavasin) over a period of 4 weeks excluding
      weekends. This was followed by a treatment-free follow-up period of 3 months.
      Changes in the quality of life were recorded with both the newly developed
      disease-specific questionnaire PAVK-86, and the generic questionnaire SF 36; in
      addition, the pain-free and maximum walking distances on the treadmill were also
      established prior to and immediately following treatment, as also at the end of
      the follow-up period. RESULTS: The quality of life was significantly improved in
      all dimensions (functional status, complaints, pain, mood, anxiety, social life,
      treatment expectations) in addition to a marked increase in the median pain-free
      walking distance from 77 to 108 m (p < 0.001) and the maximum walking distance
      from 118 to 171 m (p < 0.001). At the end of the 3-month observation period, the
      improvement was essentially still demonstrable. CONCLUSION: The study has shown
      for the first time that treatment with intravenous PGE1 brings about not only the
      already known increase in the walking distance, but also a clinically relevant
      and significant improvement in the patient's quality of life.

PMID- 9174390
TI  - A new surgical technique for the treatment of life-threatening congenital
      arteriovenous malformation--intraluminal graft implantation.
AB  - A new surgical intraluminal graft implantation technique was undertaken in a 27
      year-old man with a massive, life-threatening, high-flow congenital arteriovenous
      malformation (AVM) involving the left lower extremity, which was resistant to
      such challenges as transarterial embolizations or partial resections. For
      occlusion of the feeder branches, a composite graft composed of two grafts with
      different diameters, which matched to the arterial lumen, was surgically inserted
      into the superficial femoral artery. The implanted graft occluded 2 weeks after
      the insertion. Although amputation distal to the knee was necessary because of
      the foot necrosis, the graft was useful in reducing the cardiac output (from 14.3
      l/min to 9.8 l/min) and obviating hip joint amputation. A further clinical study
      is necessary to examine whether or not it is an acceptable treatment modality.

PMID- 9174391
TI  - Blue toes due to floating plaque of the abdominal aorta: endovascular repair with
      stent.
AB  - A 60 year old male patient was admitted with so-called blue toes on both sides.
      Investigation, including real-time ultrasound, revealed a floating plaque on the
      dorsal side of the abdominal aorta as the most probable cause of the blue toes.
      By means of simultaneous fluoroscopy and ultrasound guided implantation of a
      stent it was possible to restore a free lumen of the aorta. The patient had an
      uncomplicated recovery. Post-operative colour coded Doppler ultrasound showed
      normal flow in the aorta. Follow-up examination one year after the procedure
      demonstrated no evidence of further embolic events and a patent aorta.

PMID- 9174392
TI  - Skin hyperemia in a habitual blusher.
AB  - Blushing, a vascular skin response to emotion is difficult to investigate since
      subjects are not able to blush on demand in a laboratory setting. Laser Doppler
      fluxmetry measures blood flux changes noninvasively. In a 28 year old lady
      distressed by habitual blushing we were able to document changes in skin blood
      flux during blushing. Forehead skin blood flux increased suddenly from 20 to 45
      arbitrary units and returned to baseline values after about 3 minutes. It is the
      first time that emotionally provoked hyperemia in head skin is documented.

PMID- 9174393
TI  - Identification of enterotoxin-producing strains of Escherichia coli by PCR and
      biological methods.
AB  - The polymerase chain reaction (PCR) and biological methods for detection of
      enterotoxigenic strains of Escherichia coli were compared. The tests for LT, STa
      and STb were done in the cell line Y1, suckling mice, and ligated piglet
      intestinal loops, respectively. The production of STb was tested only in strains
      negative for LT and STa. The polymerase chain reaction has proved to be specific
      and reliable method than the biological methods. Unlike the latter, PCR allows
      the detection of strains producing in vitro only low quantities of the toxin. On
      the other hand, PCR fails to identify strains producing toxic substances with a
      different structure but the same or similar biological properties.

PMID- 9174394
TI  - [Mortality due to malignant tumors in children and adolescents in Belgrade 1980
      1993].
AB  - In the period 1980-1993, in Belgrade, malignant tumors of the age group up to 24
      years were 1.2% of the mortality structure of all cancers. The average
      standardized mortality rate (world standard population) of all cancers was 7.0
      per 100,000 with a decreasing trend. In childhood and adolescence period,
      hematological malignancies (42.0%), brain tumors (23.0%) and soft tissue and bone
      tumors (10.5%) were the most frequent cancers for the observed period. The
      average standardized mortality rates for leukemia was 1.1/100,000, for non
      Hodgkin's lymphomas 0.2/100,000 and -1.7/100,000 for Hodgkin's disease. The
      elevated mortality rates were registered for leukemia and non-Hodgkin's
      lymphomas, whereas a marked decreasing trend was present for Hodgkin's disease.
      For brain malignant tumors and soft tissue and bone tumors, a decreasing
      mortality rates were also observed.

PMID- 9174395
TI  - Assessment of osteogenic potential of the natural origin bioceramics implanted
      into the human infrabony periodontal defects.
AB  - The osteogenic potential of natural origin bioceramics implanted in human
      periodontal infrabony defects was investigated Histologic and electron
      microscopic analyses of implants 3 and 4.5 months after implantation were used
      for the estimation of osteogenic potential. Results show that the bioceramics of
      natural origin with a microstructure and canalicular system of the natural bone
      has a strong osteogenic potential. Results of histologic and electron-microscopic
      analyses, performed four and half months after implantation, show that new bone
      has been formed in the places of absorbed or partially absorbed implant granules
      as also in the pores of implant granules. Histological structure of the newly
      formed bone correspond to the structure of the matured lamellated bone.

PMID- 9174396
TI  - Do prostaglandins E2, F2 alpha and D2 have a role in the development of
      idiopathic trigeminal neuralgia?
AB  - Idiopathic trigeminal neuralgia (ITN), resistant to the drug treatment was
      diagnosed in 20 patients using following parameters: clinical feature, usage of
      Bell-McGill questionnaire, as well as X-ray and neurophysiologic examinations.
      Peripheral neurectomy was performed in all of them as a palliative therapeutic
      procedure. In removed nerves of patients (n. infraorbitalis, n. alveolaris
      inferior), as well as in the same nerves of cadavers, the concentrations of
      prostaglandins (PGs) E2, F2 alpha and D2 were determined using commercial
      radioimmunoassay. Significant increase in PGE2 and PGF2 alpha concentration and
      simultaneous decrease in PGD2 concentration in the nerves of the patients with
      ITN was noticed. Results demonstrated that the increase in the concentration of
      hyperalgesic PGE2 and PGF2 alpha as well as the decrease in hypoalgesic PGD2
      concentration had an important role in the onset of neuralgic pain in patients
      with ITN.

PMID- 9174397
TI  - The features of rheumatoid arthritis in the patients above the age of 60.
AB  - Fifty-seven patients with rheumatoid arthritis (RA), who were divided into 2
      groups: below 50 and above the age of 60 with the disease onset at the age of 24
      to 81 were analyzed. They were treated in the Clinic for Rheumatology between
      1985 and 1995. All the patients fulfilled the American Rheumatism Association
      (ARA) criteria for RA from 1988. The aim of the study was to reveal any specific
      qualities of RA with the onset at the age above 60 and to compare them with the
      specific qualities in younger patients in order to come to certain conclusions
      useful for diagnosis and the treatment. The investigations revealed significant
      differences in articular and systemic manifestations in the patients with the
      late onset of RA. The disease onset was often acute, with monoarthritis of the
      large joints, high erythrocyte sedimentation rate (ESR), increased level of
      alkaline phosphatase (ALP), and with slow and incomplete remissions. The effect
      of nonsteroid anti-inflammatory drugs (NSAID-s) was poorer, followed by more
      frequent adverse effects in the group of patients above 60 than in the younger
      patients. The administration of gold and D-penicillamine showed no effect in the
      elderly, and the cytostatic treatment was not also indicated. The complications
      and relapses occurred more frequently, and remissions were shorter compared to
      those in the younger patient group.

PMID- 9174398
TI  - A threat in the air. How stereotypes shape intellectual identity and performance.
AB  - A general theory of domain identification is used to describe achievement
      barriers still faced by women in advanced quantitative areas and by African
      Americans in school. The theory assumes that sustained school success requires
      identification with school and its subdomains; that societal pressures on these
      groups (e.g., economic disadvantage, gender roles) can frustrate this
      identification; and that in school domains where these groups are negatively
      stereotyped, those who have become domain identified face the further barrier of
      stereotype threat, the threat that others' judgments or their own actions will
      negatively stereotype them in the domain. Research shows that this threat
      dramatically depresses the standardized test performance of women and African
      Americans who are in the academic vanguard of their groups (offering a new
      interpretation of group differences in standardized test performance), that it
      causes disidentification with school, and that practices that reduce this threat
      can reduce these negative effects.

PMID- 9174399
TI  - Does the Graduate Record Examination predict meaningful success in the graduate
      training of psychologists? A case study.
AB  - The authors consider the empirical validity of the Graduate Record Examination
      (GRE) as a predictor of various kinds of performance in a graduate psychology
      program, including 1st- and 2nd-year grades; professors' ratings of students'
      dissertations; and professors' ratings of students' analytical, creative,
      practical, research, and teaching abilities. On the basis of the triarchic theory
      of intelligence, the GRE was predicted to be of some use in predicting graduate
      grades but of limited or no use in predicting other aspects of performance. In
      fact, the test was found to be useful in predicting 1st-year grades but not other
      kinds of performance, with one exception--performance on the GRE Analytical test
      was predictive, but only for men. The authors conclude that there is a need to
      develop better theory-based tests.

PMID- 9174400
TI  - Imprint switch mechanism indicated by mutations in Prader-Willi and Angelman
      syndromes.
AB  - Genomic imprinting is an epigenetic mechanism resulting in the preferential
      expression of the maternal or paternal alleles of a specific subset of genes in
      the mammalian genome. A key but relatively unexplored question is how imprints
      are established in the germline. New observations on two classical imprinting
      disorders, the Prader-Willi (PWS) and Angelman (AS) syndromes, offer the first
      genetic insight into this process. Molecular analysis of imprinting mutations
      that interfere with the appropriate establishment of the maternal and paternal
      epigenotypes has led to the identification of imprinted transcripts that could be
      involved in switching imprints in the germlines.

PMID- 9174401
TI  - Telomeres, not the end of the story.
AB  - Transcription in organisms as diverse as yeast and mammals is subject to
      chromosomal position effects that result in heritable and variegated patterns of
      gene expression. Two recent studies have employed a reversible protein-DNA
      crosslinking method to identify the structural components of heterochromatin in
      budding yeast. The results show that a complex containing the proteins Rap1,
      Sir2p, Sir3p and Sir4p is physically associated with nucleosomes at telomere
      proximal regions, but that the repressive chromatin structure extended by Sir3p
      overexpression has a different composition.

PMID- 9174402
TI  - A novel signalling mechanism for generating Ca2+ oscillations at fertilization in
      mammals.
AB  - At fertilization in mammals the sperm activates the egg by triggering a series of
      oscillations in the intracellular free Ca2+ concentration. The precise sequence
      of events that occur between sperm-egg contact and the increases in intracellular
      Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis
      that a cytosolic sperm protein enters the egg after gamete membrane fusion and
      triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies
      suggest that there exists a novel sperm protein, named oscillin, that
      specifically comigrates with Ca2+ oscillation-inducing activity. Oscillin has
      been immunolocalised to the region of the sperm that first fuses with the egg.
      The concept of a specific protein that triggers Ca2+ oscillations may have wider
      physiological significance since sperm oscillin can induce Ca2+ oscillations in
      somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling
      system involved in mammalian fertilization may help reveal some fundamental
      molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations.

PMID- 9174403
TI  - Drosophila Hox complex downstream targets and the function of homeotic genes.
AB  - Hox complex genes are key developmental regulators highly conserved throughout
      evolution. The encoded proteins share a 60-amino-acid DNA-binding motif, the
      homeodomain, and function as transcription factors to control axial patterning.
      An important question concerns the nature and function of genes acting downstream
      of Hox proteins. This review focuses on Drosophila, as little is known about this
      question in other organisms. The noticeable progress gained in the field during
      the past few years has significantly improved our current understanding of how
      Hox genes control diversified morphogenesis. Here we summarise the strategies
      deployed to identify Hox target genes and discuss how their function contributes
      to pattern formation and morphogenesis. The regulation of target genes is also
      considered with special emphasis on the mechanisms underlying the specificity of
      action of Hox proteins in the whole animal.

PMID- 9174404
TI  - RET in human development and oncogenesis.
AB  - Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are
      hereditary disorders related to the abnormal migration, proliferation or survival
      of neural crest cells and their derivatives. Hirschsprung disease is a frequent
      disorder of the enteric nervous system, resulting in intestinal obstruction. The
      multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural
      crest derivatives. Both diseases are associated with heterozygous mutations in
      the RET proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase
      expressed in neural crest lineages and whose ligand, glial-cell-line-derived
      neurotrophic factor, has been very recently identified. In vitro expression
      studies demonstrate that while Hirschsprung disease mutations result in loss of
      function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2
      mutations lead to its constitutive activation. Thus, the two 'faces' of RET, gain
      of function and loss of function, each lead to a different syndrome,
      respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or
      Hirschsprung disease, a developmental defect.

PMID- 9174405
TI  - Genetics of phototaxis in a model eukaryote, Dictyostelium discoideum.
AB  - The life cycle of Dictyostelium discoideum offers a unique opportunity to study
      signal transduction in eukaryotic cells at both the unicellular and multicellular
      levels of organization. Adding to the already extensive knowledge of the
      unicellular stages, classical and molecular genetics have begun to unravel
      transduction of signals controlling morphogenesis and behaviour (phototaxis and
      thermotaxis) in the multicellular 'slug' stage of the life cycle. Distributed
      over all seven genetic linkage groups are probably about 20, but possibly as many
      as 55, genes of importance for slug behaviour. The encoded proteins appear from
      pharmacological studies and mutant phenotypes to govern transduction pathways
      involving the intracellular second messengers cyclic AMP, cyclic GMP, IP3 and
      Ca2+. Pathways from the photo- and thermoreceptors converge first with each other
      and thence, at the level of the second messengers, with those from extracellular
      tip activation (cyclic AMP) and inhibition (Slug Turning Factor and/or ammonia
      and/or adenosine) signals that control slug movement and morphogenesis.

PMID- 9174406
TI  - The role of phosphotyrosine phosphatases in haematopoietic cell signal
      transduction.
AB  - Phosphotyrosine phosphatases (PTPases) are the enzymes which remove phosphate
      groups from protein tyrosine residues. An enormous number of phosphatases have
      been cloned and sequenced during the past decade, many of which are expressed in
      haematopoietic cells. This review focuses on the biochemistry and cell biology of
      three phosphatases, the transmembrane CD45 and the cytosolic SH2-domain
      containing PTPases SHP-1 and SHP-2, to illustrate the diverse ways in which
      PTPases regulate receptor signal transduction. The involvement of these and other
      PTPases has been demonstrated in haematopoietic cell development, apoptosis,
      activation and nonresponsiveness. A common theme in the actions of many
      haematopoietic cell PTPases is the way in which they modulate the thresholds for
      receptor signalling, thereby regulating critical events in the positive and
      negative selection of lymphocytes. There is growing interest in haematopoietic
      PTPases and their associated regulatory proteins as targets for pharmaceutical
      intervention and in the involvement of these enzymes in human disease.

PMID- 9174407
TI  - Schistosomiasis vaccine development--the current picture.
AB  - Development of a vaccine for schistosomiasis, a parasitic disease currently
      affecting over 200 million people worldwide, has been targeted as a priority by
      the World Health Organisation. Research demonstrating the ability of humans to
      acquire natural immunity to schistosome infection, together with the successful
      use of attenuated vaccines in animals both under laboratory and field conditions,
      suggest that development of a human vaccine is feasible. Attenuated vaccines for
      schistosomiasis are considered neither safe nor practicable for human use,
      however, and therefore other approaches must be considered. This review examines
      progress currently being undertaken in a number of different areas towards
      achieving the goal of a safe and effective human vaccine for schistosomiasis.

PMID- 9174408
TI  - Synthesis of prenylated peptides and peptide esters.
AB  - Modification of the cysteine sulfur in peptides and proteins to a thioether is a
      recently described posttranslational event that results in the incorporation of
      farnesyl and geranylgeranyl moieties. The increased lipophilicity accompanying
      these modifications often causes localization of the resulting protein to the
      membrane and may be essential for biological activity. Methods are described to
      chemically and biochemically synthesize farnesylated and geranylgeranylated
      peptides and proteins from microgram to gram quantities. Conditions for
      thioalkylation include acidic, neutral, and basic media. The ability to readily
      form peptidylthioethers will greatly facilitate studies of biologically important
      proteins and peptides containing isoprenyl moieties.

PMID- 9174409
TI  - Biophysical studies of lipopeptide-membrane interactions.
AB  - There are a number of naturally occurring motifs for lipidation of peptides and
      proteins. In cases in which this involves adding a single hydrocarbon chain to
      the peptide, it is either a fatty acid or an isoprenyl group. Lipopeptides will
      partition between membrane and aqueous phases. When only one hydrocarbon chain is
      attached to the peptide, the affinity of the lipopeptide for the membrane is only
      marginally increased over that of the free peptide. The resulting partitioning is
      largely determined by the extent of the interaction of the peptide moiety with
      the membrane. In contrast, lipidation involving two hydrocarbon chains, either as
      two single chains attached at distinct locations of the peptide or a double-chain
      lipid anchor, firmly attaches the lipopeptide to the membrane. This can allow the
      placement of specific binding sites on a membrane surface. Such a strategy can be
      used, for example, to place specific antibodies on the surface of drug-carrying
      liposomes for the purpose of targeting drug delivery. In addition, lipopeptides
      will alter the physical properties of membranes. One of these effects is to
      increase the bilayer to hexagonal phase transition temperature. Substances having
      this property may also alter functional properties of membranes. While it is
      unlikely that these changes in the biophysical properties of the membranes. While
      it is unlikely that these changes in the biophysical properties of the membrane
      are responsible for specific functions of lipopeptides, such changes may be used
      to modulate certain properties of a membrane, such as the rate of viral fusion.

PMID- 9174410
TI  - Farnesyltransferase as a target for anticancer drug design.
AB  - The currently understood function for Ras in signal transduction is in mediating
      the transmission of signals from external growth factors to the cell nucleus.
      Mutated forms of this GTP-binding protein are found in 30% of human cancers with
      particularly high prevalence in colon and pancreatic carcinomas. These mutations
      destroy the GTPase activity of Ras and cause the protein to be locked in its
      active, GTP bound form. As a result, the signaling pathways are activated,
      leading to uncontrolled tumor growth. Ras function in signaling requires its
      association with the plasma membrane. This is achieved by posttranslational
      farnesylation of a cysteine residue present as part of the CA1A2X carboxyl
      terminal tetrapeptide of all Ras proteins. The enzyme that recognizes and
      farnesylates the CA1A2X sequence, Ras farnesyltransferase (FTase), has become an
      important target for the design of inhibitors that might be interesting as
      antitumor agents. Several approaches have been taken in the search for in vivo
      active inhibitors of farnesyltransferase. These include the identification of
      natural products such as the chaetomellic and zaragozic acids that mimic
      farnesylpyrophosphate, bisubstrate transition state analogs combining elements of
      the farnesyl and tetrapeptide substrates and peptidomimetics that reproduce
      features of the carboxyl terminal tetrapeptide CA1A2X sequence. This last group
      of compounds has been most successful in showing highly potent inhibition of
      FTase and selective blocking of Ras processing in a range of Ras transformed
      tumor cell lines at concentrations as low as 10 nM. Certain peptidomimetics will
      also block tumor growth in various mouse models, with apparently few toxic side
      effects. These results suggest that farnesyltransferase inhibitors hold
      considerable promise as anticancer drugs in the clinic.

PMID- 9174411
TI  - Selective peptidic and peptidomimetic inhibitors of Candida albicans
      myristoylCoA: protein N-myristoyltransferase: a new approach to antifungal
      therapy.
AB  - MyristoylCoA: protein N-myristoyltransferase (NMT) catalyzes the cotranslational
      covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal
      Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often
      essential for expression of the biological functions for these proteins.
      Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable
      association with membranes. The partitioning of N-myrisotylproteins is therefore
      often modulated by "switches" that function through additional covalent or
      noncovalent modifications. Candida albicans, the principal cause of systemic
      fungal infection in immunocompromised humans, contains a single NMT gene that is
      essential for its viability. The functional properties of the acylCoA binding
      site of human and C. albicans NMT are very similar. However, there are distinct
      differences in their peptide binding sites. An ADP ribosylation factor (Arf) is
      included among the few cellular protein substrates of the fungal enzyme. Alanine
      scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence
      (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in
      binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/-
      6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N
      terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive
      inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent
      [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu
      Ser from the C-terminus generates a competitive dipeptide inhibitor (11
      aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that
      of the starting octapeptide. A derivative dipeptide inhibitor containing a C
      terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more
      potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular
      carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very
      potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole
      for the N-terminal amine and adding a benzylic alpha-methyl group with R
      stereochemistry to the rigidifying element produces even more potent inhibitors
      (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to
      human enzyme. A related less potent member of this series of compounds is
      fungistatic. Its growth inhibitory effects are associated with a reduction in
      cellular protein N-myristoylation, judged using cellular Arf as a reporter. These
      studies establish that NMT is a new antifungal target.

PMID- 9174412
TI  - Effect of work glove and type of muscle action on grip fatigue.
AB  - Fatigue plays a major role in limiting work performance. The objectives of this
      study were: (1) to determine the effect of wearing a work glove on handgrip
      fatigue; (2) to compare the effect of a sustained grip contraction of concentric
      versus eccentric nature, named in this study isometric and eccentric; and (3) to
      determine if there is a relationship between physiological muscle performance and
      subjective perceptional fatigue during isometric and eccentric gripping. The
      study had 2 x 2 repeated measures design. The two factors were: (1) glove
      condition (glove, no glove); and (2) type of contraction (eccentric and
      isometric). The measurements taken were: (1) time to limit of endurance (Tlim);
      (2) rate of perceived effort (RPE); (3) mean power frequency (MPF) derived from
      the electromyogram (EMG); and (4) the fatigue objective-subjective relationship
      (FOSR, which is the correlation coefficient between RPE and MPF). Twenty-one
      normal subjects maintained a handgrip of 60% of their maximal effort until
      exhaustion for each of the four conditions. During each trial EMG values were
      recorded every 5 s and RPE values were recorded every 10 s. The RPE was recorded
      as a subjective value selected from a 10-point Borg scale. The results showed
      that Tlim was greater for the no glove condition (p < 0.0005) and for the
      eccentric muscle action (p < 0.05). The FOSR was greatest for the glove condition
      (p < 0.03) and for the isometric muscle action (p < 0.013). The MPF decline
      showed no significant difference for any condition. These data indicate that
      glove condition and type of handgrip contraction have an effect on physiological
      fatigue and subjective perception of fatigue.

PMID- 9174413
TI  - Assessing vigilance through a brief pencil and paper letter cancellation task
      (LCT): effects of one night of sleep deprivation and of the time of day.
AB  - Behavioural effects of the lack of sleep in normal subjects have been
      investigated mostly by experimenter-paced choice reaction times in prolonged
      stimulus detection tasks. However, length and procedure complexity of these tasks
      limit their use in research on larger numbers of subjects. The aim of the present
      study was to assess the effectiveness of a brief subject-paced pencil and paper
      performance task, i.e. letter cancellation task (LCT) in revealing the effects of
      one night of sleep deprivation. In addition, the authors evaluated sleep loss and
      time of day effects on six Visual Analogue Scales (VAS) measuring subjective
      activation-deactivation. Results show that a LCT is sensitive in revealing the
      effects of time of day and of 24 h of sleep deprivation. Effects of sleep
      deprivation were also revealed by VAS data. Sleepiness, tiredness and energy
      scales on the VAS were also affected by time of day. Despite the sensitivity of
      both the LCT and VAS, there was little correspondence between performance and
      subjective measures.

PMID- 9174414
TI  - Influence of carrying book bags on gait cycle and posture of youths.
AB  - The purpose of this investigation was to determine the impact of different
      methods of carrying book bags on static posture and gait kinematics of youths
      aged 11-13 years. Surveys identified group descriptive characteristics of
      subjects and book bags. Ten subjects representing the best composite of the mean
      characteristics of this population were filmed for both static posture and
      dynamic conditions of one stride length. Subjects participated in four
      conditions: without bag (WO), one-strap backpack (1BP), two-strap backpack (2BP),
      and one-strap athletic bag (ATH). Lateral spinal deviation was not significantly
      different between 2BP and WO. However, differences (+/-SE) were observed between
      1BP (8.5 +/- 0.7 degrees) and ATH (8.3 +/- 2.4 degrees) as compared with WO (1.9
      +/- 0.5 degrees). Shoulder elevation from a horizontal position showed no
      difference between WO and 2BP. Without bag (2.0 +/- 0.9 degrees) was different
      from 1BP (17.6 +/- 1.8 degrees) and ATH (15.6 +/- 2.1 degrees). 1BP was also
      different from 2BP (3.4 +/- 1.1 degrees). Bag carrying significantly decreased
      stride length (1.59 +/- 0.04 m) and increased stride frequency (57.36 +/- 1.6
      cycles/min) compared to WO (1.72 +/- 0.06 m; 54.64 +/- 1.2 cycles/min,
      respectively), thereby reducing the support phase of the gait. One-strap bags
      (1BP, ATH) promoted lateral spinal bending and shoulder elevation, while the two
      strap backpack significantly reduced these book bag carrying stresses. ATH
      promoted greater angular motion of the head and trunk as compared to backpack
      book bags. Carrying a backpack (1BP, 2BP) promoted significant forward lean of
      head and trunk compared to ATH or WO. In conclusion, the daily physical stresses
      associated with carrying book bags on one shoulder (1BP, ATH) significantly
      alters the posture and gait of youth.

PMID- 9174415
TI  - Quantitative MRI and electrophysiology of preoperative carpal tunnel syndrome in
      a female population.
AB  - The tunnel size is reported to play a role in median neuropathy. The aim of the
      study was to quantify the volume of the carpal tunnel in a selected population
      with idiopathic carpal tunnel syndrome (CTS), as the narrowest point of the canal
      was noted. Twenty-seven patients with CTS and 28 asymptomatic controls were
      examined. All participants were women. Both groups underwent nerve conduction
      studies and magnetic resonance (MR) of the wrists. On the MR axial images, the
      volume of carpal tunnels, the wrists and the thenar muscles were calculated
      bilaterally in all subjects. The values for the signal intensity of the median
      nerve from all wrists were also quantified and correlated with the
      neurophysiological findings. The carpal tunnel volume (CTV) and the wrist volume
      (WV)/CTV ratio were almost identical in both groups (p = 0.36 and p = 0.45,
      respectively). The focal narrowest point of the tunnel was similarly located in
      both populations, and detected at its distal third, about 8 mm from the outlet.
      The median nerve in the patients emitted a higher signal compared with the
      controls, p = 0.037. Between the two groups, there were differences in the
      amplitude and the distal latency of the median sensory branch (p = 0.0001 and p =
      0.0001, respectively), as well as in the amplitude and the F-wave latencies of
      the median motor branch (p = 0.045 and p = 0.017, respectively). There was no
      difference in the size of the carpal tunnel in women with idiopathic CTS compared
      with healthy controls, as the focal narrowest point was equally located in both
      groups near the canal outlet.

PMID- 9174416
TI  - NIOSH equation horizontal distances associated with the Liberty Mutual (Snook)
      lifting table box widths.
AB  - A study was conducted to determine the NIOSH equation horizontal distances (dH)
      associated with the three different box widths (34, 49 and 75 cm) and lift
      starting heights (floor, knuckle and shoulder) used in the psychophysically based
      Liberty Mutual lifting tables (Snook 1978, Snook and Ciriello 1991). Data were
      collected with 12 male and 12 female subjects and three repetitions were
      performed for each of the nine lifting conditions. No gender effects were
      observed so male and female data were pooled. The value of dH was positively
      related to box width but there was also a significant interaction between box
      width and starting height. When pooled across lift heights the average values of
      dH were 44, 49 and 57 cm for the 34, 49 and 75 cm box widths, respectively. When
      pooled across box widths the average values of dH were 52, 45 and 52 cm for the
      floor, knuckle and shoulder height lifts, respectively. A knowledge of the dH
      associated with each box width will allow for direct comparisons to be made
      between the NIOSH and Liberty Mutual outputs. This will facilitate further
      validation of the NIOSH equations. A variable (GAP) was calculated to indicate
      the horizontal distance from the ankles to the edge of the box. Previously, this
      GAP has been assumed to remain constant and values of 15, 20 and 25 cm have been
      proposed. The GAP was observed to have an overall mean of 23.6 cm with individual
      condition means ranging from 14.6 cm to 31.2 cm. When pooled across conditions
      the mean GAP values were equal to dH minus half the box width.

PMID- 9174417
TI  - A comparison of risk assessment of single and combination manual handling tasks:
      2. Discomfort, rating of perceived exertion and heart rate measures.
AB  - Although many manual handling activities involve combinations of pull, lift,
      carry, lower and push, there are few reports of investigation of how to assess
      the risk in these combination tasks. Two strategies have been suggested in the
      literature for estimating the risk in a combination task based on the measures of
      the separate components of that task. The aim of the study was to compare the
      risks assessed in single manual handling tasks with those in combination tasks.
      Ratings of discomfort, exertion and heart rate were collected from nine male and
      nine female students, performing combination and single tasks. Combination tasks
      consisted of sequences of pull, lift, carry, lower and push tasks. Combination
      tasks were performed at 1.min-1 and 3.min-1 whilst single tasks (lift, lower,
      push, pull and carry) were performed at 3.min-1 and 6.min-1. The rating of
      exertion and heart rate for each combination task was compared to the exertion
      rating and heart rate of the single tasks which comprised the combination task
      using repeated measures analysis of variance with specified contrasts. Similar
      comparisons for the discomfort data were performed using Friedman and Wilcoxon
      tests. In at least one of the twelve comparisons performed for each dependent
      variable, the combination task value was significantly different to each single
      task value. The differences occurred regardless of whether the most critical
      single task value or an average of all single task values was used. It was
      concluded that the risk in combination manual tasks can not be accurately
      assessed by using estimates from discomfort, exertion ratings and heart rate
      measures of single tasks.

PMID- 9174418
TI  - The influence of different floor stiffness on mechanical efficiency of leg
      extensor muscle.
AB  - The mechanical behaviour of skeletal muscle is influenced by internal factors
      (e.g. re-use of elastic energy) and/or external conditions (e.g. floor
      compliance, shoe structure etc.). These factors have an effect on muscular work
      economy-this was investigated in the present study. Eight subjects were tested
      during three different series of jumps. Each series consisted of rhythmical
      vertical jumps performed at desired frequency and height for 1 min. The first (1)
      series was executed on the laboratory floor without rebound condition (subjects
      were asked to maintain 1 s period in an isometric condition before concentric
      work was performed), the second (II) and the third (III) series were performed in
      rebound conditions respectively on a laboratory floor (hard surface) and on a
      special panel possessing high compliance (a special foam rubber panel with
      stiffness of 14.4 kN/m). Expired air was collected during the test and recovery
      for determination of energy expenditure. Mechanical work was calculated from the
      vertical displacement of the body during the jumps. The results indicated that
      the net efficiency in the jumps without prestretch of the leg extensor muscles
      (series I) was the lowest (19.4%). In contrast, the net efficiency observed in
      rebound jumps (series II and III) was respectively 30.8% and 33.1%, demonstrating
      that the reuse of elastic energy (Wel) plays an important role for muscular work
      efficiency. However, the contribution of Wel to the total work performed was
      different p < 0.05, Student's t-test) in jumps on the special panel (41%)
      compared to the normal surface (37%), even if the total amount of stored elastic
      energy was the same in both conditions. The different efficiency observed between
      series II and III was attributed to the compliance of the surface on which the
      tests were executed. It was suggested that man could change his neuromuscular
      pattern to adapt muscular behaviour for matching the damped properties shown by
      the high compliance surface. Finally, the soft surface may favour a very low rate
      of running injuries.

PMID- 9174419
TI  - Reproductive health beyond Cairo and Beijing.

PMID- 9174420
TI  - Vaginal pudendal nerve stimulation: a new technique for assessment of pudendal
      nerve terminal motor latency.
AB  - BACKGROUND: To evaluate vaginal stimulation of the pudendal nerve, a new method
      for investigation of pudendal nerve terminal motor latency (PNTML) and to assess
      the reproducibility of the method. METHODS: Thirteen healthy women and 11 female
      patients, median age 31 years (range 21-53 years), participated in the study. Ten
      patients had sustained an anal sphincter rupture and one had idiopathic anal
      incontinence. Pudendal nerve terminal motor latency was measured after vaginal
      stimulation of the pudendal nerve with motor response from the pelvic floor and
      rectal stimulation with motor response from the anal sphincter using the St.
      Marks pudendal electrode. The women were stimulated by two observers both
      vaginally and by the rectum. RESULTS: Vaginal PNTML for observer 1 was 2.06 msec
      (0.50 msec, 2 s.d.) and 2.04 msec (0.55 msec, 2 s.d.) for observer 2, while
      rectal PNTML was 1.99 msec (0.56 msec, 2 s.d.) and 1.97 msec (0.54 msec, 2 s.d.)
      respectively. The difference between vaginal and rectal PNTML was 0.065 msec for
      observer 1 (p = 0.106) and 0.070 msec for observer 2 (p < 0.05). Degree of
      agreement between vaginal and rectal PNTML was 80%-116% for observer 1 and 84%
      12% for observer 2 (100% represent total agreement between measurements).
      Interobserver reproducibility for vaginal PNTML was 90%-109% and 86%-113% for
      rectal PNTML. CONCLUSION: In clinical practice vaginal PNTML may replace rectal
      PNTML in women. Reproducibility is in the same range as for rectal PNTML.

PMID- 9174421
TI  - Gestational weight gain as a predictor of birth and placenta weight according to
      pre-pregnancy body mass index.
AB  - OBJECTIVE: To study the association between gestational weight gain and different
      birth weight indicators considering the pre-pregnancy body mass index. It was
      hypothesized that a high body mass index (BMI) would modify the effect of
      gestational weight gain and support the advice of keeping gestational weight gain
      at a moderate level in case of obesity. STUDY DESIGN: A follow-up study of
      consecutively recruited women in two well defined geographical areas in Denmark.
      The recruitment lasted from 1984 to 1987 and 11,850 pregnant women and newborns
      were included in the study. The remaining analyses were restricted to non
      diabetic women who gave birth between weeks 37 and 42 of gestation for whom
      weight gain was reported-altogether 7,122 women. RESULTS: Birth and placenta
      weight were associated with gestational weight gain but with lower regression
      coefficients at higher BMI. The proportion of newborns with a birth weight of
      4,500 grams or more increased with increasing gestational weight gain, especially
      in women with a BMI above 26. CONCLUSION: The potential benefit of a high
      gestational weight gain in obese patients should be balanced by the higher risk
      of giving birth to babies with a birth weight of more than 4,500 grams and the
      risk of exaggerating a pre-existing state of obesity.

PMID- 9174422
TI  - Cerebral blood flow changes associated with fetal intracranial hemorrhages.
AB  - BACKGROUND AND MATERIAL: In order to evaluate cerebral blood flow changes
      associated with fetal intracranial hemorrhages, ultrasound and MRI examinations
      were carried out in four pregnancies with this complication. RESULTS: Increased
      resistance indices of the blood flow profile of the middle cerebral artery were
      detected in three of the fetuses, two of them presenting retrograde diastolic
      flow. Flow became normalized in one case within four weeks, changing on the
      contralateral side to an increased diastolic flow pattern. CONCLUSION: Increased
      intracranial pressure can cause these flow changes, but cerebral blood flow
      autoregulation need not be completely ruined in this complication.

PMID- 9174423
TI  - Motor vehicle accident during the second or third trimester of pregnancy.
AB  - OBJECTIVE: To evaluate the need of immediate treatment, follow-up and
      consequences of different types of traffic accidents during pregnancy. METHOD AND
      MATERIAL: A retrospective analysis covering five years involving thirty-five
      pregnant women involved in motor vehicle accidents at 22-39 weeks of gestation.
      RESULTS: Fifteen of the 35 women were involved in frontal impact collisions, and
      suffered mild subjective and objective symptoms; all their fetuses survived and
      were delivered at term. Fifteen other women were involved in broadside
      collisions; two of these were riding a bicycle. These 15 women had clear
      objective findings like uterine contractions or tenderness, and some of them
      needed tocolytic therapy and hospitalization up to eight days. This was
      significantly longer than in those involved in frontal impact collisions.
      However, the broadside accidents did not have any adverse effect on pregnancy
      outcomes either. Five women were involved in serious accidents at speeds of 80
      110 km/h, and one mother and her fetus died immediately because of rupture of the
      uterus and the cervical joint and spinal canal. Four other fetuses were found
      dead on arrival at hospital or soon after. In all cases the cause of fetal loss
      was placental abruption. The presence of fetal blood cells in maternal blood was
      evaluated in 15 of 35 patients, but was positive in only one. CONCLUSION: Frontal
      collisions are associated with lower vehicular speed, less trauma and no acute or
      later effects on pregnancy, whereas broadside collisions and high speed (> 80
      km/h) cause more symptoms. The latter type of accidents are associated with high
      risk of placental abruption and of fetal and maternal death. Fortunately the
      symptoms are evident immediately after the accident, and early hospital discharge
      is possible if no abnormalities are present during the first hours.

PMID- 9174424
TI  - Socioeconomic status and perinatal outcome according to residence area in the
      city of Malmo.
AB  - BACKGROUND: Maternal socioeconomic status is known to influence perinatal
      outcome. Antenatal care is free of charge in Sweden and all pregnant women are
      followed according to a standardized protocol of surveillance. The city of Malmo
      in southern Sweden is divided into 124 townships with great differences in
      socioeconomic standard. The aim of this study was to evaluate perinatal outcome
      according to the address of residence of the mothers within the city of Malmo.
      METHODS: Perinatal outcome of 7056 pregnancies was related to three socioeconomic
      characteristics of the 124 townships in Malmo: percentage of immigrants,
      percentage of inhabitants on social welfare and the median income. RESULTS:
      Maternal age was lower, number of abortions and parity were higher in low income
      areas. Perinatal complications were also more frequent, including low
      birthweight, small-for-gestational age newborns, maternal anemia, infections, and
      low 1- and 5-minute Apgar scores. Premature rupture of membranes was associated
      with low income areas. Symphysiolysis and pre-eclampsia were more frequent in the
      high income areas. CONCLUSION: Although maternity care is provided free of
      charge, perinatal complications were more frequent in areas of lower
      socioeconomic status. In order to improve perinatal outcome, antenatal
      surveillance should be intensified in low class socioeconomic areas.

PMID- 9174425
TI  - Delivery and pudendal nerve function.
AB  - OBJECTIVE: To assess the impact of mode of delivery and the occurrence of pelvic
      instability upon the pudendal nerve function and relate the pudendal nerve
      function to the occurrence of anal and urinary incontinence. METHODS: One hundred
      and forty-six pregnant women were examined during pregnancy and 12 weeks post
      partum with measurement of pudendal nerve terminal motor latency (PNTML), the
      difference between the two measurements was defined as delta PNTML. Anal and
      urinary continence status, details of delivery and the occurrence of pelvic
      instability were recorded prospectively. RESULTS: Pudendal nerve terminal motor
      latency increased from 1.7 msec in primiparae and 1.8 msec in multiparae during
      pregnancy to 2.0 msec (p < 0.001) and 2.1 (p < 0.001) respectively after
      delivery. The increase was significantly higher after the use of vacuum
      extraction (p < 0.04). Multivariate analysis showed that delta PNTML was
      associated with age, the presence of pelvic instability and the use of vacuum
      extraction. Whereas delta PNTML was not associated with factors such as infant's
      head circumference and weight, parity, cesarean section, pudendal block, epidural
      analgesia and second stage of labor. Only four women had anal incontinence after
      delivery. Twenty-five women with urinary incontinence had a significantly higher
      mean PNTML (2.20 msec) than 121 continent women (2.01 msec). CONCLUSION: Pudendal
      nerve terminal motor latency increases in both primiparous and multiparous women
      after delivery. In 10% of the women the increase resulted in a pathologic PNTML
      value > 2.4 msec. The delta PNTML was significantly associated with age, the
      occurrence of pelvic instability and the use of vacuum extraction. The group of
      women with urinary incontinence had a significant increased PNTML.

PMID- 9174426
TI  - Maternal mortality after cesarean section in The Netherlands.
AB  - BACKGROUND: To assess cesarean section-related maternal mortality in The
      Netherlands during 1983-1992. METHODS: A nationwide confidential enquiry into the
      causes of maternal death. RESULTS: The risk of dying after vaginal birth was 0.04
      per 1000 vaginal births (65/1.763.999) compared to 0.53 per 1000 cesarean births
      (57/108.587). The direct risk of dying from cesarean section was 0.13 per 1000
      operations (14/108.587). In some women cesarean section did not initiate, but
      contributed to, the train of events leading to death. Adding this associated risk
      to the direct risk gives a fatality rate of 0.28 per 1000 cesarean births
      (30/108.587). CONCLUSIONS: Although cesarean section is a relatively safe
      procedure nowadays, birth by cesarean section in The Netherlands is seven times
      more hazardous than vaginal birth. Keeping the cesarean birth rate as low as
      possible is therefore in the interest of women of reproductive age.

PMID- 9174427
TI  - Results of intracytoplasmic sperm injection in relation to indication.
AB  - BACKGROUND: Intracytoplasmic sperm injection (ICSI) was first introduced as a
      treatment to couples that were infertile due to severe male factors. Later, the
      ICSI technic has also been used on other indications like low or no fertilization
      in previous IVF cycles. METHODS: A total of 262 ICSI cycles performed in 180
      patients were reviewed and the results related to the indications. The
      indications were severely impaired semen quality (182 cycles) or absent or low
      fertilization in previous IVF attempts (80 cycles). RESULTS: A total of 2298
      oocytes were aspirated and 1939 oocytes were injected resulting in 1172
      fertilized (60%) and 995 cleaved oocytes (51%). Of these, 547 preembryos were
      transferred in 240 cycles and 287 preembryos were cryopreserved. We obtained 99
      pregnancies (41%/transfer) of which 63 were ongoing pregnancies (26%/transfer).
      The pregnancy rate was significantly lower (p = 0.025) in couples referred for
      ICSI due to previously failed IVF (29%/ transfer) compared to couples with
      impaired semen quality (46%/transfer). Seventy-seven children have been born.
      Forty-eight healthy children were born from singleton pregnancies with a mean
      gestational age of 39.8 weeks and an average birthweight of 3561 g. Thirteen sets
      of healthy twins and one set of healthy triplets were born. In 29 of the 63
      ongoing pregnancies amniocenteses were performed and all karyotypes were normal.
      CONCLUSION: IVF with ICSI gave good clinical results in couples with severe male
      factor infertility. The technic can also be used in couples with unexplained
      fertilization failure, but the pregnancy rate may be lower.

PMID- 9174428
TI  - Pre- and postoperative therapy with GnRH agonist for endometrial resection. A
      prospective, randomized study.
AB  - BACKGROUND: To assess the value of endometrial preparation, with preoperative and
      pre- and postoperative GnRH agonist therapy in transcervical endometrial
      resection. METHODS: Sixty women with menorrhagia were randomly divided between
      three groups: A: no preoperative preparation, B: goserelin 3.6 mg given as a
      subcutaneous implant 4-6 weeks preoperatively, and C: the same regimen as B, and
      repeated on the day of endometrial resection. At follow-up visits 1, 3, 6 and 12
      months after operations the patients were interviewed for duration, amount and
      pains of menstrual periods. RESULTS: The duration of surgery for the pretreated
      group (32.8 +/- 5.1 min) and the group treated postoperatively (30.9 +/- 8.9 min)
      were significantly shorter than that in the control group (46.4 +/- 11.5 min) (p
      < 0.01). The weight of endomyometrial strips was about 3 times lower for group B
      and C as compared to group A (p < 0.01). Three months following the procedure
      twenty five percent of patients in group A were amenorrheic or showed scanty
      bleeding as compared to 58% and 85% in group B and C (p < 0.05 and p < 0.01),
      respectively. At 12 months follow-up these rates were 35%, 58% and 67%
      respectively (A versus B: NS, A versus C: p < 0.05) and 24%, 65% and 75% after
      excluding larger submucosal fibroids (A versus B: p < 0.025, A versus C: p <
      0.005). No statistical difference was demonstrated between group B and C. Sixty
      nine percent of pretreated patients (group B + C) versus 35% of women in group A
      reported improved or relieved menstrual cramps (p < 0.05). CONCLUSIONS: GnRH
      pretreatment facilitates endometrial resection and increases the rate of
      amenorrhea and scanty bleeding postoperatively. Whether supplementary
      postoperative therapy with GnRH agonist enhances the success rate further is
      uncertain.

PMID- 9174429
TI  - The incidence of ectopic pregnancy in Hordaland County, Norway 1976-1993.
AB  - OBJECTIVE: To gain longterm knowledge of incidence rates of ectopic pregnancy, as
      a basis for analysing risk factors. MATERIAL: The incidence of ectopic pregnancy
      was studied in the county of Hordaland, Western Norway, through 18 years, 1976
      1993. The protocols of 1821 cases of ectopic pregnancy were registered.
      Population data of the county, the number of births and legal abortions were
      available. RESULTS: There was considerable increase in crude numbers of ectopic
      pregnancies throughout the period. Grouping the cases in three six-year periods
      showed an increased crude incidence rate per 100,000 women from 95 during 1976-81
      to 154 during 1988-93. The corresponding rates per 1000 births increased from
      13.6 to 22.2 and the rates per 1000 reported pregnancies from 11.2 to 18.0. All
      rates increased also in women aged 40-44 years. During the years 1979-1993 the
      rates per 1000 reported pregnancies increased by 25%, from 9.4 to 11.8 in age
      groups below 30 years, while the rates for women over 35 years increased by 98%,
      from 20.7 to 40.9. Compared to the age group 15-19, women over 35 years had an
      eightfold risk during the last period. In addition they also contributed to
      higher numbers of reported pregnancies by 58%. CONCLUSION: The rates of ectopic
      pregnancy increased in age groups older than 20 years during 1976-93, moderately
      in younger age groups, but considerably in older age groups, who also contributed
      with higher total rates of pregnancy. More older women, with presumably
      accumulated risk factors getting pregnant, thus explain part of the increased
      rates of this disease.

PMID- 9174430
TI  - Gynecological complaints and war traumas. A study from Zenica, Bosnia-Herzegovina
      during the war.
AB  - BACKGROUND: During the war in former Yugoslavia people endured great suffering.
      Although many had sought refuge in other countries, the majority remained within
      Bosnia-Herzegovina. Special service for women within the war zone was urgently
      needed. A Women's Therapy Center was established in Zenica, Bosnia-Herzegovina
      offering reproductive health services and psychosocial assistance. The aim of the
      study was to establish the most commonly occurring gynecological problems during
      different periods in the war and relate these to war traumas. METHODS:
      Information from 486 records of consecutive gynecological consultations in four
      different periods during in 1993/94 were retrospectively recorded. RESULTS:
      Vaginal discharge, pelvic pain, and amenorrhea were the most commonly occurring
      problems. A higher proportion of pregnant women requested legal abortion in the
      first period compared to later periods when the situation was improved. In 14
      (3%) of the consultations a history of rape during the war was recorded.
      Additionally 42 (9%) had suffered from other types of war traumas. The reporting
      of war traumas was significantly related to suffering from pelvic pain (p <
      0.05). CONCLUSIONS: The focus on the need of victims of rape during war has
      highlighted the need for reproductive services as part of emergency situations.
      The suffering of war traumas has to be taken into account in the handling of
      gynecological problems in this situation.

PMID- 9174431
TI  - Neonatal herpes in Denmark 1977-1991.
AB  - BACKGROUND: To prevent neonatal herpes, women in labor with genital herpes
      infection are still delivered by Cesarean section. This policy is currently being
      debated. The aim of this study was to determine the incidence of neonatal herpes
      in Denmark and to evaluate the prevention practice. METHODS: All newborns with
      perinatal herpes in Denmark 1977-1991 were identified from hospital-records.
      RESULTS: Of 862,298 deliveries 136 possible cases were found but only 30 (22%)
      fulfilled the criteria for neonatal herpes. The incidence increased from 2.36 to
      4.56 per 100,000 live births during 1977-1984 through 1984-1991. Three mothers
      (10%) had recurrent herpes at delivery, three (10%) had primary herpes, and five
      (17%) had oral herpes. Seven infants (23%) were delivered by Cesarean section.
      Nine (30%) only had cutaneous herpes, four (13%) had CNS herpes, nine (30%) had
      disseminated disease. Six (20%) did not have any sequelae. Four (13%) died. Six
      (20%) had serious neurological sequelae. Seven (23%) only had cutaneous
      recurrences. In seven cases (23%) information was insufficient. CONCLUSIONS:
      During a 15 year period in Denmark only one neonate had serious sequelae
      following a recognized maternal herpes recurrence. Four infants had a serious
      infection in spite of Cesarean section. This study does not support a policy of
      Cesarean section in case of maternal recurrent herpes simplex infection at
      delivery.

PMID- 9174432
TI  - Obesity as a predictor of postpartum urinary symptoms.
AB  - BACKGROUND: To investigate the relationship between pre-pregnancy obesity, and
      urinary symptoms, especially urinary incontinence, before, during, and 6-18
      months after delivery. METHODS: Body Mass Index extracted from obstetric records.
      Postal questionnaire. MATERIAL AND SETTING: One hundred and eight women with Body
      Mass Index of at least 30 kg/m2 delivered at the Obstetric Department, Herning
      Central Hospital, October 1994 to September 1995. As control served 108 matched,
      normal weight women delivering during the same period. RESULT: Response rate was
      83%. Stress incontinence, urgency and the feeling of having a hygienic problem
      was significantly more common after delivery in both groups, but at any time
      significantly more common among obese women. Urge incontinence was a numerically
      small problem after delivery. CONCLUSION: Obesity is a potent risk factor for
      several urinary symptoms after pregnancy and delivery, and a substantial number
      of women still have problems 6-18 months postpartum.

PMID- 9174433
TI  - High-dose chemotherapy with autologous stem cell support for the treatment of
      advanced ovarian cancer--initial experience in Uppsala and Turku.
AB  - BACKGROUND: With current standard-dose chemotherapy ovarian cancer is a
      chemosensitive but not chemocurable disease in the majority of cases. The widely
      used first-line chemotherapy including a platinum analogue combined with
      cyclophosphamide results in response rates of 60-80%. However, only 10-20% of
      patients with advanced disease are alive 5 years after the diagnosis. The
      efficacy of high-dose chemotherapy supported by autologous stem cell
      transplantation (ASCT) is currently under intensive investigation. METHODS: We
      report here our initial experiences of the use of high-dose chemotherapy
      supported by ASCT for patients with high-risk ovarian cancer. Two patients were
      treated at Uppsala University Hospital in 1992 and four patients at Turku
      University Central Hospital in 1994. RESULTS: The first four patients treated
      either after heavy previous chemotherapy or recurrent disease relapsed within 5
      10 months. Two patients received high-dose therapy as part of first-line
      treatment. One of them had a relapse 18 months after therapy, the other one has
      been disease free for 28 months. No toxic deaths occurred, but the patients had
      neutropenic febrile episodes and moderate to severe gastrointestinal toxicity.
      CONCLUSIONS: Coordinated efforts in Nordic countries are indicated to evaluate
      the usefulness of high-dose therapy supported by ASCT in the treatment of
      advanced ovarian cancer.

PMID- 9174434
TI  - Second-look laparotomy in the management of fallopian tube carcinoma.
AB  - OBJECTIVE: To evaluate the role of second-look laparotomy following platinum
      based combination chemotherapy in patients with fallopian tube carcinoma.
      METHODS: A retrospective chart review was conducted on 21 patients with tubal
      carcinoma who underwent second-look laparotomy following cytoreductive surgery
      and platinum-based combination chemotherapy. RESULTS: Thirteen patients (62%)
      were found to be free of disease at second-look operation. Neither stage nor
      grade were predictive of findings at second-look procedure. The absence of gross
      residual disease following primary surgery was the only predictor of disease-free
      status at second-look laparotomy (p < 0.01). With a mean follow-up of 49 months
      among the survivors, four (31%) of the patients with negative second-look
      laparotomy have had a recurrence. The median survival following a positive second
      look laparotomy was 18 months (range 5-42 months). CONCLUSION: Second-look
      laparotomy provides useful prognostic information in patients with tubal
      carcinoma. The high rate of recurrent disease after negative second-look
      laparotomy, and the lack of an effective second-line treatment in patients with
      persistent disease, represent major criticisms of this procedure.

PMID- 9174435
TI  - Childbearing and mortality from cancer of the corpus uteri.
AB  - BACKGROUND: To investigate the mortality from cancer of the corpus uteri in
      relation to parity and age at first and last birth. METHODS: A cohort of 431,604
      married women aged 45-74 years at the Norwegian Census in 1970 was followed over
      15 years. A total of 752 deaths from cancer of the corpus uteri were diagnosed
      during follow-up. RESULTS: All age groups showed significant trends of decreasing
      mortality rates with increasing number of children. The age-adjusted reduction in
      mortality was 9.2% (95% CI 5.2-13.0) for each child. Women with 8-11 children had
      a relative risk of 0.35 (95% CI 0.14-0.85) compared to nulliparous women. For
      first birth at age > = 35 years versus < = 19 years, the relative risk was 0.53
      (95% CI 0.34-0.83). No significant effect of age at last birth was found.
      CONCLUSIONS: This study supports the notion that high parity and postponing the
      first delivery may reduce the risk of uterine cancer death.

PMID- 9174436
TI  - Type III congenital cystic adenomatoid malformation of the lung detected through
      maternal serum screening positive for Down's syndrome.

PMID- 9174437
TI  - Hydatidiform mole co-existent with a live fetus.

PMID- 9174438
TI  - Intra-uterine growth retardation and transverse lie due to massive subchorionic
      thrombohematoma and overlying large subchorionic cyst.

PMID- 9174439
TI  - Intrauterine device--primary and secondary perforation of the urinary bladder.

PMID- 9174440
TI  - Relationship between intrauterine midgut volvulus without malrotation and preterm
      delivery.

PMID- 9174441
TI  - Inflammatory cytokines regulate proliferation of cultured human osteoblasts.
AB  - We investigated the effects of various pro-inflammatory cytokines on the
      proliferation rate of isolated human osteoblastic cells in primary cultures.
      Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-beta (TNF-beta) time-
      and dose-dependently enhanced the proliferation of human osteoblasts. Both of
      these cytokines also enhanced endogenous prostaglandin E2 (PGE2) formation.
      Exogenous PGE2 dose- and time-dependently-stimulated cell proliferation. However,
      the stimulatory effects of IL-1 beta and TNF-beta on osteoblast proliferation
      were not abolished by indomethacin, indicating a direct effect by these cytokines
      on the rate of proliferation. TNF-alpha stimulated proliferation at low doses,
      while it significantly inhibited proliferation at higher concentrations (at and
      above 100 pM) and with prolonged incubation times. This biphasic effect was
      unaffected by indomethacin. Interleukin-6, finally, did not affect the rate of
      proliferation. Our findings show that inflammatory cytokines may stimulate or
      inhibit the proliferation of isolated human osteoblasts, depending on
      concentration and time.

PMID- 9174442
TI  - Bone mineral density, muscle strength and physical activity. A population-based
      study of 332 subjects aged 15-42 years.
AB  - The aim of this population-based study was to find out whether differences in
      levels of physical activity have an influence on bone mass quantity and whether
      quadriceps muscle strength is a reliable determinant of bone mass. Included were
      175 men and 157 women, aged 15-42 years. Bone mineral density (BMD) was measured
      at various sites by dual X-ray absorptiometry (DXA) and single photon
      absorptiometry (SPA). Muscle strength was assessed using an isokinetic muscle
      force meter. A questionnaire was used to estimate the level of physical activity.
      We found a positive correlation between physical activity and BMD for boys at the
      distal forearm and for girls at the trochanter (age group 15-16 years). Active
      men (age group 21-42 years) had up to 9% higher BMD levels at the hip than those
      who were less active. Quadriceps muscle torque was not an independent predictor
      of BMD. Our data suggest that a higher level of physical activity-within the
      limits of a "normal life style"-may have a positive effect on BMD in the proximal
      femur of young adults, which in turn may lessen the subsequent risk of fracture.

PMID- 9174443
TI  - Ethylene oxide does not extinguish the osteoinductive capacity of demineralized
      bone. A reappraisal in rats.
AB  - We examined the influence of ethylene oxide (EO) and gamma irradiation on the
      osteoinductive capacity of demineralized bone. Demineralized bone powder prepared
      from Wistar rats was exposed to EO (55 degrees C or 40 degrees C) or gamma
      irradiation (25 KGy) or was preserved in ethanol. Sterilely-prepared bones served
      as controls. The powder was packed in a gelatin capsule and implanted for 6 weeks
      in muscles of 6-week-old female rats. Exposure of demineralized bone particles to
      EO 55 degrees C resulted in an almost complete loss of osteoinductivity.
      Irradiated bones lost about 40% of their osteoinductive capacity, while
      sterilization with EO at 40 degrees C resulted in only a slight alteration of the
      osteoinductivity, as assessed by the recovered weight ratio, calcium content,
      alkaline phosphatase activity measurements and histomorphometry. Ethanol
      treatment had no influence on the new bone yield when compared to controls. As EO
      exposure at 40 degrees C is a true sterilization procedure, it can be recommended
      in a clinical setting for its small effect on osteoinductive capacity as assessed
      experimentally in rats.

PMID- 9174444
TI  - Subaxial cervical spine subluxation in rheumatoid arthritis. A retrospective
      analysis of 16 operated patients after 1-5 years.
AB  - We evaluated the clinical and radiological outcomes in 16 patients (15 women)
      having rheumatoid arthritis with a mean age of 66 (55-77) years, on average 2 (1
      5) years after decompression and stabilization, for subaxial subluxation of the
      cervical spine. The duration of rheumatoid arthritis averaged 30 (10-67) years
      and the duration of neck symptoms averaged 15 (1-60) months. Preoperatively, 11
      of the patients had pain in the neck, all 16 suffered from arm rhizopathy and
      varying degrees of myelopathy. 4/5 patients with severe myelopathy died within 3
      months of surgery. Fixation failure occurred in 7 patients, but had no clinical
      significance in 5. There were 1 deep infection and 1 nerve root lesion resulting
      in deltoid weakness. Other complications were dysphagia and donor-site pain. 4
      reoperations were performed, 2 extension of fusion, 1 revision of infection, and
      1 foraminotomy. Neck pain was reliably relieved, while arm rhizopathy was less
      positively affected. Myelopathy carried a poor prognosis for relief and its
      occurrence correlated with death. Early treatment, before significant myelopathy
      has developed, is recommended. Decompression, both via realignment and bone
      resection, followed by fusion of the entire cervical spine, is advocated. Due to
      the poor bone quality and with the presently available implant systems,
      simultaneous anterior and posterior fixation is beneficial.

PMID- 9174445
TI  - Clinical history in lumbar disc herniation. A prospective study in 160 patients.
AB  - In a prospective study of 160 consecutive patients who underwent primary surgery
      for lumbar disc herniation, we investigated the value of clinical history for
      diagnosing the degree of herniation-the main prognostic factor for the
      postoperative outcome. At surgery, the patients were classified into two groups:
      intact anulus (negative exploration or protruding disc) and ruptured anulus
      (subligamentary perforation or complete perforation). The strongest variables
      predicting the degree of herniation were duration of leg pain, progressive leg
      pain, educational level and whether or not the patient had previously undergone
      non-spinal surgery. In patients with ruptured anulus, the median durations of low
      back pain and sciatica were 16 and 10 weeks, respectively. The corresponding
      figures for the group with intact anulus were 79 and 50 weeks. 18% of those with
      ruptured anulus and 39% of those with intact anulus were undergoing medical or
      psychiatric treatment for other diagnoses; 32% and 55% had previously undergone
      non-spinal surgery. Thus the two groups differed not only in disc pathology but
      also in medical, behavioral and social factors that must be taken into account in
      the preoperative assessment and that may explain discrepancies between impairment
      and disability.

PMID- 9174446
TI  - Acute hemiarthroplasty after proximal humerus fracture in old patients. A
      retrospective evaluation of 18 patients followed for 2-7 years.
AB  - We evaluated the outcome of acute shoulder hemiarthroplasty in 18 patients
      following displaced three- and four-part fractures of the proximal humerus. The
      mean age of the patients was 82 (70-92) years and the average follow-up time was
      3.5 (2-7) years. No revision due to loosening was performed. All patients were
      evaluated concerning activities of daily living, degree of pain (VAS-scale, 0-100
      mm) and range of motion. The patients had a low functional level, but were able
      to sleep on the operated side and keep up their hobby. 11 patients were painfree
      and the worst pain recorded was 28 mm. Range of motion for all movements, except
      extension, was statistically significant lower than for the non-operated side. We
      conclude that in elderly patients acute hemiarthroplasty following three- or four
      part fractures of the proximal humerus results in good pain relief, but a more
      limited range of motion than that reported for younger patients.

PMID- 9174447
TI  - Ununited proximal pole scaphoid fractures. Treatment with a Herbert screw in 16
      cases followed for 0.5-8 years.
AB  - We treated 16 cases of delayed union and nonunion of proximal one-third scaphoid
      fractures with cancellous bone grafting and retrograde insertion of a Herbert
      screw through a dorsal approach. Definite radiographic union was obtained in 13
      of 16 patients after a median of 2 (0.5-8) years of follow-up. Using Cooney's
      clinical scoring system, 5 cases were excellent, 5 good, 5 fair and 1 poor. The
      treatment of ununited proximal pole scaphoid fractures with retrograde insertion
      of the Herbert screw offers the advantages of a short period of immobilization
      and a good function.

PMID- 9174448
TI  - Dynamics of hip joint remodeling after Chiari osteotomy. 10 patients with
      neuromuscular disease followed for 8 years.
AB  - We analyzed the development of 10 hips in 10 consecutive patients with
      neuromuscular disease (9 with spasticity, 1 with Charcot-Marie-Tooth disease) who
      had undergone Chiari osteotomy for painful hip subluxation or dislocation. The
      patients were 11 (5-19) years old at surgery and follow-up time was 8 (6-11)
      years. The Chiari osteotomy particularly improved and maintained femoral head
      coverage. These parameters did not show the postoperative deterioration noted in
      some other studies. The osteotomy did not improve femoral head lateral
      displacement. Throughout the postoperative period, the configuration of the
      proximal femur and the height of the joint cartilage were unchanged and
      undisturbed, indicating that osteotomy did not place excessive or uneven pressure
      on the femoral head. The ambulatory status of the patients was dependent on the
      severity of the underlying disease, and was not improved by osteotomy. However,
      pain associated with subluxation or dislocation was reduced in 9 of the patients.

PMID- 9174449
TI  - Low- or high-vacuum drains in hip arthroplasty? A randomized study of 73
      patients.
AB  - We compared the effect of low-vacuum and high-vacuum drains on blood loss and
      blood transfusions in a randomized study of 73 patients undergoing primary hip
      arthroplasties. During the first postoperative hour, the high-vacuum drains
      evacuated more blood than the low-vacuum ones, median 135 and 35 mL (p < 0.001).
      After that, the rate of blood loss into the drains was approximately the same.
      Median blood losses into the drains after 24 hours were 570 mL in the high-vacuum
      group and 480 mL in the low-vacuum group (p = 0.03). Corresponding values after
      48 hours were 785 mL and 585 mL (p = 0.002). The hemoglobin concentration in the
      drain fluid during the second postoperative day was lower in the high-vacuum
      group, indicating a more serous discharge. Our findings indicate that drains
      should be removed within 24 hours. High-vacuum drains evacuate more blood
      initially but may cause more damage to the tissues, especially if they are left
      for more than 24 hours. We found no significant difference in postoperative
      hemoglobin decrease or in the number of blood transfusions and wound
      complications in the 2 groups.

PMID- 9174450
TI  - Stress osteopathy of the femoral head. 10 military recruits followed for 5-11
      years.
AB  - I present 10 cases of spongious bone injury of the femoral head induced by
      physical stress. All patients were young military recruits who complained of hip
      pain from weight bearing which had started during physical exertion. Increased
      uptake in a radionuclide bone scan was regarded as the criterion for stress
      osteopathy. 7 hips were radiographically normal. In 3 cases a subcortical lateral
      cystic lesion of the femoral head was observed. MRI was performed in 6 cases. A
      decreased signal intensity in T1-weighted images in 5 cases and high signals in
      T2-weighted and IR signals (2 patients) indicated bone marrow edema. A lateral
      osteophyte of the femoral head developed in 1 case during 8 years' follow-up.
      After a median of 6 years, 9 patients still had occasional slight hip pain.

PMID- 9174451
TI  - Medial collateral knee ligament healing. Combined medial collateral and anterior
      cruciate ligament injuries studied in rabbits.
AB  - We examined the histological appearance and biochemical properties of the healing
      medial collateral ligament (MCL) of a rabbit knee after combined MCL and anterior
      cruciate ligament (ACL) injury treated with ACL reconstruction and with or
      without MCL repair. By so doing, we hoped to understand better our previous
      bomechanical observations (Ohno et al. 1995) and possibly learn where to focus
      future investigation into improving the quality of the healing MCL. Ligaments
      were examined at 6 and 12 weeks of healing. We found healing of all ligaments
      with hypercellularity and fibroblast elongation along the axis of loading, as
      expected. Unexpected, however, was the finding of multiple osteophytes in both
      the repaired and nonrepaired specimens at the medial borders of the joint and at
      the MCL insertions. These were felt to affect possibly the biomechanics of the
      MCL by causing stress risers at the point where they undermine the ligament.
      Biochemically, we demonstrated a correlation between collagen content and
      hydroxypyridinium crosslinks and modulus of elasticity. While this implies that
      the modulus is dependent on collagen content and hydroxypyridinium crosslink
      density, modulus is also probably dependent on other factors such as collagen
      organization, type and internal structure. Overall, the detailed characterization
      and correlation between the histological, biochemical, and biomechanical
      properties of the healing MCL in the severe knee injury model provide insight
      into the functional behavior of the healing MCL.

PMID- 9174452
TI  - Neural and muscular electric activity in the cat's knee. Changes when the
      anterior cruciate ligament is transected.
AB  - We studied the response of the normal and unstable knee to passive motion and
      anterior tibial displacement in the cat. 6 cats were anesthetized and the deep
      level of anesthesia was controlled by electroencephalograms. We recorded electric
      activity in the articular nerves (posterior PAN and medial MAN) and periarticular
      muscles (quadriceps and hamstring), while performing passive flexion, extension,
      internal and external rotation. We then produced anterior displacement of the
      tibia at 30 degrees and 90 degrees of flexion, as in the Lachman and the anterior
      drawer maneuvers. The anterior cruciate ligament was surgically sectioned and the
      same series of passive displacements was performed. We observed statistically
      significant increased activity in the MAN, the PAN and the quadriceps muscle
      during knee flexion, in the MAN during extension, and in the PAN and hamstring
      during external rotation with the knee 90 degrees flexed. Anterior cruciate
      transection caused anterior displacement of the tibia during stress. This
      produced a significant increase in the MAN activity and a significant decrease in
      the hamstring electric activity at 30 degrees and 90 degrees of flexion, as in
      Lachman and anterior drawer maneuvers. We conclude that electric activity in the
      articular nerves and periarticular muscles, in response to passive motion and
      anterior tibial displacement, is altered in the cat's knee after anterior
      cruciate transection. This suggests that various patterns of periarticular muscle
      reaction in the anterior cruciate-deficient knee may be related to the
      unconscious perception of abnormal motion.

PMID- 9174453
TI  - Quality of life after knee arthroplasty. A randomized study of 3 designs in 42
      patients, compared after 4 years.
AB  - We assessed different yardsticks for outcome 4 (3-5) years after surgery in a
      prospective, randomized study of 42 patients, where 3 designs of cemmentless knee
      prostheses were used. The prognosis with regard to loosening, previously obtained
      by radiostereometry after 2 years of follow-up, was utilized. Patients with a
      prognosis of stable implant fixation (two thirds) were compared with those where
      loosening was predicted (one third). Hospital for Special Surgery score and
      Visual Analogue Scales regarding pain at rest, "first step" pain, pain during
      activity and global function, showed consistent postoperative improvements, but
      no differences between the design and prognosis groups were found. Radiolucent
      lines were registered both as yes/no and number of zones. Lines and prognosis
      were associated, but not lines and design groups. Quality of life assessment by
      the Nottingham Health Profile questionnaire showed that the poor prognosis group
      had increased pain and significant disturbances of sleep and emotions, as well as
      difficulty in enjoying hobbies and holiday activities. No differences were found
      between the design groups. Altogether, the patients showed profiles comparable to
      a healthy reference group. We conclude that the Nottingham Health Profile is a
      sensitive, relevant and simple measure of outcome after knee arthroplasty.

PMID- 9174454
TI  - Progression of human bone ingrowth into porous-coated implants. Rate of bone
      ingrowth in humans.
AB  - We report the measured progression of human cancellous bone ingrowth into load
      bearing porous-coated titanium implants over 5 time periods (0, 3, 6, 9, and 12
      months). There was a statistically significant progression of bone ingrowth into
      the implants over a 9-month period, but the 9- and 12-month data were not
      different. Investigators are advised to analyze time "0" implants in order to
      distinguish mechanical impaction of bone from the biological process of bone
      ingrowth.

PMID- 9174455
TI  - Metaphyseal-diaphyseal angle in Blount's disease. A 30-year follow-up of 13
      unoperated children.
AB  - We analyzed the metaphyseal-diaphyseal angle in 13 patients with infantile
      Blount's disease, who had been followed without treatment during the entire
      growth period and without any form of realignment procedure in adulthood. On
      diagnosis at 23 (17-35) months of age, the metaphyseal-diaphyseal angle varied
      between 7 degrees and 25 degrees. At follow-up, most of the legs were almost
      straight. We found that the diagnosis of Blount's disease cannot be based solely
      on the metaphyseal-diaphyseal angle and that a bowed knee must be followed with
      repeated examinations before it can be decided whether treatment is needed.

PMID- 9174456
TI  - Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients.
AB  - We evaluated biopsy specimens from the Achilles tendon in 40 patients with long
      standing achillodynia and an ultrasonographic widened tendon with hypoechogenic
      areas. We used a standardized protocol to assess the general tendon pathology
      score of paraffin-embedded specimens stained with HE. Stereologic measurement of
      the volume density of glycosaminoglycan (GAG)-rich areas, stained with the Alcian
      blue (pH 2.5)/periodic acid Schiff method (AB/PAS) was performed. 14 specimens
      obtained at autopsy served as reference material. Abnormal fiber structure and
      arrangement, focal variations in cellularity, rounded nuclei, decreased collagen
      stainability and increased non-collagenous extracellular matrix were seen in all
      biopsy specimens. Slight histopathological changes were noted in half of the
      controls. Increased vascularity was present in two thirds of the patient
      specimens and in one third of the controls, and signs of perivascular hemorrhage,
      as evidenced by hemosiderin deposition in 6/40 of the patients, but in none of
      the controls. The volume density of GAG-rich areas was higher in the patients
      0.47 (0-0.86) than in the controls 0 (0-0.07). Changes in the fiber structure and
      arrangement, as well as increased amounts of interfibrillar GAG, appear to be
      characteristic morphological features in Achilles tendons with long-standing
      achillodynia and ultrasonographic widening. These findings may indicate that
      achillodynia is due to local disturbances in connective tissue metabolism or
      circulation or to both.

PMID- 9174457
TI  - Traumatic cervical disc herniation--tetraparesis in a patient kicked by a horse.

PMID- 9174458
TI  - Spontaneous premature closure of the tibial tubercle--report on 2 boys with a new
      disorder?

PMID- 9174459
TI  - Operations, total hospital stay and costs of critical leg ischemia.

PMID- 9174460
TI  - Pain drawing in lumbar disc hernia.

PMID- 9174461
TI  - Knee ligaments and proprioception.

PMID- 9174462
TI  - A critical analysis of cartilage repair.

PMID- 9174463
TI  - Visceral fat in white and African American prepubertal children.
AB  - The objectives of this study were 1) to examine interrelations among
      intraabdominal adipose tissue (IAAT) and other adiposity indexes, 2) to identify
      a visceral obesity index that is independent of total adiposity, and 3) to
      examine sex and ethnic (white compared with African American) differences in
      IAAT. We measured IAAT and subcutaneous abdominal adipose tissue (SAAT) using
      computed tomography, and total fat mass (FM) by dual-energy X-ray absorptiometry
      in a heterogenous sample of 101 children aged 7.7 +/- 1.6 y weighing 33.2 +/-
      12.6 kg. IAAT was highly variable (mean +/- SE; 31 +/- 22 cm2; range: 7-107 cm2)
      and related to SAAT (r = 0.87) and FM (r = 0.81). The regression slope between
      IAAT and SAAT was significantly lower in African Americans (0.17 +/- 0.02 cm2
      IATT/cm2 SAAT) than in whites (0.23 +/- 0.02 cm2 IAAT/cm2 SAAT). Within each
      ethnic group there was no effect of sex on IAAT adjusted for SAAT (mean +/- SE:
      40.2 +/- 3.1 and 43.2 +/- 2.7 cm2 in white boys and girls, respectively; 26.4 +/-
      1.9 and 25.1 +/- 1.6 cm2 in African American boys and girls, respectively). We
      conclude that in children 1) there is wide variation in visceral fatness; 2) IAAT
      relative to SAAT is an index of visceral fat, independent of FM, allowing
      examination of the unique effects of IAAT; and 3) the relative distribution of
      adipose tissue in the intraabdominal compared with the subcutaneous abdominal
      region is significantly lower in African Americans than in whites.

PMID- 9174464
TI  - Body composition assessed on the basis of arm circumference and triceps skinfold
      thickness: a new index validated in children by magnetic resonance imaging.
AB  - Fat and muscle areas can be calculated from equations on the basis of upper arm
      circumference (C) and triceps skinfold thickness (TS). These equations assume a
      circular limb and muscle compartment and a symmetrically distributed fat rim:
      total upper arm area (TUA) = C2/(4 pi), upper arm muscle area (UMA) = [C - (TS x
      pi)2]/(4 pi), and upper arm fat area (UFA) = TUA - UMA. This traditional method
      underestimates the degree of adiposity. We propose that the unrolled fat rim is a
      rectangle whose length = C and width = TS/2. The following new indexes are based
      on this assumption: upper arm fat area estimate (UFE) = C x (TS/2), and upper arm
      muscle area estimate (UME) = TUA - UFE. To validate these equations, areas were
      measured with magnetic resonance imaging (MRI) in 28 children aged 9-15 y (17
      control subjects and 11 obese subjects). Correlations between MRI and UFA and MRI
      and UFE were similar (r = 0.96 for both correlations in the control group and r =
      0.84 and 0.82, respectively, in the obese group), but the areas assessed by MRI
      (13.8 cm2) were closer to UFE (12.4 cm2) than to UFA (11.2 cm2) in the control
      group as well as in the obese group (MRI = 48.7 cm2, UFE = 46.6 cm2, and UFA =
      38.5 cm2). The limits of agreement between MRI and anthropometry were 5.7 +/- 5.8
      cm2 for UFA and 0.6 +/- 5.0 cm2 for UFE, showing that UFA is not acceptable in
      most cases, whereas UFE measurements are close to MRI measurements. In
      conclusion, UFE and UME are simple and accurate indexes to assess body
      composition. French reference values are available from 1 mo to 17 y of age.

PMID- 9174465
TI  - Predicting early nonelective hospital readmission in nutritionally compromised
      older adults.
AB  - This study determined predictors of early nonelective hospital readmission in 92
      (49 women and 43 men) nutritionally compromised Medicare patients. Subjects
      ranged in age from 65 to 92 y and represented patients hospitalized previously
      for medical or surgical services. The study used a repeated-measures design of
      multiple variables representing demographics, anthropometric and clinical values,
      and functional status. Data were collected during hospitalization and during home
      visits at 1 and 3 mo postdischarge. There were 26 readmissions, making the 4-mo
      nonelective readmission rate 26%. Subjects who were readmitted nonelectively were
      compared with those not readmitted. Univariate analyses suggested strong
      relations between readmission outcome and serum albumin, total lymphocyte count,
      change in weight, and change in white blood cell count. Sociodemographic
      variables were less useful in predicting readmission than were measurements of
      patients' clinical status. Measurements of change in clinical variables were
      generally more predictive of readmission than was any one single measurement.
      Multivariate-logistic-regression analyses suggested a model consisting of change
      in weight and change in serum albumin from hospitalization to 1 mo after
      discharge as being highly predictive of early nonelective readmission.
      Individuals with any amount of weight loss and no improvement in albumin
      concentrations during the first month after hospitalization were at a much higher
      risk of readmission than were those who maintained or increased their
      postdischarge weight and had repleted their serum albumin concentrations. More
      study is warranted to clarify whether routine monitoring of changes in weight and
      serum albumin after hospitalization is appropriate in older adults.

PMID- 9174466
TI  - Specificity of indexes of malnutrition when applied to apparently healthy people:
      the effect of age.
AB  - Protein-energy malnutrition is thought to be widespread in hospitalized patients.
      However, the specificity of indexes used to assess malnutrition is uncertain. We
      therefore assessed the rate of false-positive diagnoses of malnutrition when
      biochemical-anthropometric indexes were applied to healthy subjects. Nutritional
      status was assessed in 175 healthy blood donors (aged 44.2 +/- 13.4 y) and in 34
      highly fit elderly volunteers (aged 74.7 +/- 3.6 y) participating in the Nijmegen
      Four Days Walking March. We investigated both the Nutritional Risk Index [(1.489
      x albumin) + (41.7 x present/usual weight)] and the Maastricht Index [20.68-(0.24
      x albumin, g/L)-(19.21 x serum transthyretin, g/L)-(1.86 x lymphocytes, 10(6)/L)
      (0.04 x ideal weight)]. We found previously that 52-64% of nonsurgical
      hospitalized patients were malnourished according to these indexes. In the
      present study, 1.9% of the 209 volunteers had apparent malnutrition according to
      the Nutritional Risk Index and 3.8% according to the Maastricht Index. The
      prevalence of apparent malnutrition in the elderly volunteers was 5.9% and 20.6%,
      respectively. The rate of false-positive diagnoses was acceptably low in those
      aged < 70 y with both the Nutritional Risk Index and the Maastricht Index;
      therefore, the use of these indexes will not cause a clinically significant
      increase in the prevalence of malnutrition because patients who are not
      malnourished are included. The high percentage of spurious malnutrition in the
      elderly limits the use of the Maastricht Index to subjects aged < 70 y.

PMID- 9174467
TI  - Postprandial parathyroid hormone response to four calcium-rich foodstuffs.
AB  - We studied the effects of four calcium-rich foodstuffs on postprandial
      parathyroid hormone secretion. Four hundred milligrams calcium from either
      Emmental cheese, milk, sesame seeds, spinach, or calcium salt (calcium lactate
      gluconate + calcium carbonate) or no additional calcium (control session) were
      given to nine female volunteers immediately after a first blood sample (at 0900)
      in random order with a light standardized meal containing 37 mg Ca. Blood samples
      were taken at 0900 (before the calcium load), 1000, 1100, 1300, and 1500 at every
      study session. Urine was collected during the sessions. Serum ionized calcium,
      phosphate, magnesium, intact parathyroid hormone, and urinary calcium excretion
      were measured. The serum ionized calcium concentration increased significantly
      after ingesting cheese (P = 0.004, contrast analysis) or calcium salt (P = 0.05,
      contrast analysis) compared with the control session. Compared with the control
      session, the serum phosphate concentration increased after the cheese session (P
      = 0.004, contrast analysis) and after the milk session (P = 0.02, contrast
      analysis). Calcium salt (P = 0.007, contrast analysis) and cheese (P = 0.002,
      contrast analysis) caused a significant decline in serum intact parathyroid
      hormone compared with the control session. The urinary calcium excretion with
      cheese was 141% (P = 0.001), with milk was 107% (P = 0.004), and with calcium
      salt was 75% (P = 0.02) above that of the control session. Our results show that
      calcium from sesame seeds and spinach does not cause an acute response in calcium
      metabolism. Our results indicate that fermented cheese could be a better dietary
      source of calcium than milk when the metabolic effects of the foodstuffs are
      considered.

PMID- 9174468
TI  - Maternal anthropometry and infant feeding practices in Israel in relation to
      growth in infancy: the North African Infant Feeding Study.
AB  - Relations between maternal anthropometric status during pregnancy and infant
      feeding practices and growth from birth through the first 6 mo of life were
      examined in a cohort of 351 Israeli mother-infant pairs of North African descent.
      Maternal weight, height, and triceps skinfold thicknesses were determined at 6
      and 9 mo of pregnancy, while infants' weights and lengths were measured at birth
      and at 1, 2, 3, and 6 mo of age with concurrent collection of age-specific
      maternal-reported infant feeding data. On the basis of multiple-linear-regression
      analysis that adjusted for potential covariates, mean maternal weight at the
      first prenatal visit and at 6 and 9 mo of pregnancy were positively associated
      with birth length (P for trend in all cases < 0.0001) and with linear growth
      between birth and 1, 3, and 6 mo of age. Maternal skinfold thickness at 9 mo of
      pregnancy and maternal height were also significantly associated with birth
      length. Moreover, maternal height, weight, and skinfold thickness at 6 and 9 mo
      of pregnancy were positively associated with mean birth weight. After adjustment
      for morbidity in the past month and other covariates, infants breast-fed
      exclusively had greater attained weight and weight gain in the first 3 mo
      compared with infants who were bottle-fed exclusively, breast-fed and bottle-fed,
      or solid-fed exclusively. These findings underscore the need for programs that
      improve the nutritional status of women before, during, and after pregnancy, and
      encourage exclusive breast-feeding of infants for at least the first 3 mo of
      life.

PMID- 9174469
TI  - Bone mineral density changes during lactation: maternal, dietary, and biochemical
      correlates.
AB  - The objectives of this study were to characterize the effects of lactation and
      weaning on maternal bone mineral density (BMD) and on biochemical markers of bone
      turnover, and to determine the effects of dietary intake, milk output, and other
      maternal factors on changes in BMD. Twenty-six fully lactating and eight
      nonlactating women were followed longitudinally through 7 mo postpartum; the
      lactating women were followed through postweaning. Maternal dietary and
      supplement intake data, infant milk intake measurements, blood and urine samples,
      and midradius and L2-L4 vertebral BMD measurements were obtained 0.5, 3, 5, and 7
      mo postpartum. Biochemical analyses included measurements of calciotropic
      hormones, 24-h urinary excretion of calcium, markers of bone formation and
      resorption, estradiol, and prolactin. Estimated maternal demands for calcium
      excretion in milk were met by a combination of high calcium intake (from diet and
      supplements, 1500 +/- 460 mg/d at 0.5 mo for lactating women) and a decline of
      approximately 4% in vertebral BMD between 0.5 and 3 mo postpartum. Postweaning
      BMD (n = 15) at this site approximated initial values. Two factors were
      positively associated with vertebral BMD, estradiol (P < 0.001) and calcium
      intake (P = 0.03), whereas two factors were negatively associated, parity (P =
      0.03) and protein intake (P = 0.01). In these well-nourished women, the results
      suggest that the extent of bone loss associated with lactation and its recovery
      postweaning are negatively influenced by parity. The results also suggest that
      the bone loss may be attenuated by a generous dietary ratio of calcium to
      protein.

PMID- 9174470
TI  - Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta
      analysis.
AB  - Quantitative relations between dietary fat and cholesterol and plasma lipid
      concentrations have been the subject of much study and some controversy during
      the past 40 y. Previous meta-analyses have focused on the most tightly
      controlled, highest-quality experiments. To test whether the findings of these
      investigations are generalizable to broader experimental settings and to the
      design of practical dietary education interventions, data from 224 published
      studies on 8143 subjects in 366 independent groups including 878 diet-blood lipid
      comparisons were subjected to weighted multiple-regression analysis. Inclusion
      criteria specified intervention studies published in English between 1966 and
      1994 reporting quantitative data on changes in dietary cholesterol and fat and
      corresponding changes in serum cholesterol, triacylglycerol, and lipoprotein
      cholesterol concentrations. Regression models are reported for serum total
      cholesterol, triacylglycerol, and low-density-high-density-, and very-low-density
      lipoprotein cholesterol, with multiple correlations of 0.74, 0.65, 0.41, 0.14,
      and 0.34, respectively. Interactions of dietary factors, initial dietary intakes
      and serum concentrations, and study and subject characteristics had little effect
      on these models. Predictions indicated that compliance with current dietary
      recommendations (30% of energy from fat, < 10% from saturated fat, and < 300 mg
      cholesterol/d) will reduce plasma total and low-density-lipoprotein-cholesterol
      concentrations by approximately 5% compared with amounts associated with the
      average American diet.

PMID- 9174471
TI  - Epinephrine does not impair utilization of exogenous amino acids in humans.
AB  - The effect of epinephrine on leucine and phenylalanine kinetics was measured by
      using the stable isotope amino acid tracers L-[1-(13)C]leucine and L-[phenyl-2H5]
      phenylalanine in the postabsorptive state and during the intravenous
      administration of a standard amino acid solution with respect to the amino acid
      load. Infusion of epinephrine (plasma concentration: approximately 3600 pmol/L)
      decreased leucine and phenylalanine and increased ketoisocaproate plasma
      concentrations and increased the metabolic clearance rate of leucine and
      phenylalanine. Epinephrine neither influenced leucine or phenylalanine flux nor
      leucine oxidation or leucine net balance. Hyperaminoacidemia from amino acid
      infusion reduced endogenous leucine release and stimulated leucine oxidation and
      nonoxidative disposal of leucine, resulting in a dose-dependent increase in
      leucine net balance. Epinephrine did not influence any changes in amino acid
      kinetics during parenteral amino acid administration. Therefore, we conclude that
      epinephrine had no catabolic effects on amino acid metabolism and no negative
      effect on the utilization of a parenterally offered amino acid solution in
      healthy humans.

PMID- 9174472
TI  - Hepatic and whole-body fat synthesis in humans during carbohydrate overfeeding.
AB  - The magnitude of the capacity to convert carbohydrate to fat in the human body is
      still controversial, as is the extent to which it takes place in the liver as
      opposed to the adipose tissue. We calculated whole-body net fat synthesis from
      indirect calorimetry and substrate balance data from five healthy men in the
      basal state and after 1 and 4 d on a hyperenergetic carbohydrate diet
      (approximately 2.5 times energy expenditure). At the same time, the secretion of
      fatty acids synthesized in the liver was measured to determine the extent to
      which fat synthesis occurs in the liver in a lipogenic state. The respiratory
      exchange ratio (RER) was 0.81 +/- 0.01 in the basal state and 0.99 +/- 0.025 and
      1.15 +/- 0.022 on days 1 and 4, respectively. Although there was net fat
      oxidation in the basal state (955 +/- 139 mg.kg-1.min-1), there was net fat
      synthesis at the whole-body level both during early (day 1; 481 +/- 205 mg.kg
      1.min-1) and late (day 4; 2243 +/- 253 mg.kg-1.min-1) carbohydrate overfeeding.
      Although hepatic secretion of fat synthesized de novo increased approximately 35
      fold during the study (basal state, 1.0 +/- 0.3; day 1, 13.8 +/- 6.8; and day 4,
      43.3 +/- 16.3 mg.kg-1.min-1) this could only account for a small portion of total
      fat synthesis. We conclude that the liver plays a quantitatively minor role when
      surplus carbohydrate energy is converted into fat in the human body. The main
      site for fat synthesis is likely to be the adipose tissue.

PMID- 9174473
TI  - Breath-hydrogen production and amylose content of the diet.
AB  - Recommendations to increase dietary intakes of starch and fiber in the United
      States may result in increased intake of resistant starch. High-amylose starch
      appears to resist digestion in vitro. To investigate the in vivo effect of high
      amylose starch, diets containing 70% amylose or amylopectin cornstarches were fed
      for 14 wk each in a crossover design to 24 men [10 control, 14 hyperinsulinemic
      (HI)]. Fasting breath samples and periodic postingestion samples were analyzed
      for hydrogen during weeks 12 (nibbling tolerance test) and 14 (acute tolerance
      test) of each phase. Overall breath hydrogen was significantly higher after the
      amylose tolerance tests (nibbling, P < 0.0005; and acute, P < 0.0006). Control
      subjects, regardless of body mass index (BMI; in kg/m2), appeared to adapt to the
      high-amylose starch diet. Fasting breath hydrogen was significantly higher at
      week 12 but not at week 14 in HI subjects with a low BMI (< 25) consuming amylose
      than in other subjects. Breath hydrogen of the HI subjects with a moderate
      (between 25 and 27.8) or high (> 27.8) BMI increased from week 12 to week 14. The
      HI subjects with a high BMI averaged lower breath-hydrogen expiration than other
      HI subjects. After 3 d of excess energy intake, breath hydrogen after amylose was
      still significantly greater than after amylopectin (P < 0.019); fasting breath
      hydrogen of the control subjects after amylose more closely resembled that of the
      HI subjects. HI subjects with a high BMI may be more efficient at digesting all
      starch, therefore decreasing the amount available for colonic digestion. This may
      be a factor contributing to their greater body weight.

PMID- 9174474
TI  - Unmetabolized folic acid in serum: acute studies in subjects consuming fortified
      food and supplements.
AB  - Periconceptual consumption of folic acid has been shown to decrease the incidence
      of neural tube defects. The strategy of universal fortification of staple
      foodstuffs with folic acid presents the possibility of life-long exposure to
      unmetabolized folic acid. Chief among the risks of exposure to folic acid in the
      circulation is that of masking the diagnosis of cobalamin deficiency in
      pernicious anemia and the progression of neurologic disease. Other effects are
      unknown. For instance, the effect of in vivo chronic exposure of adult and fetal
      cells to the synthetic form of the vitamin has never been investigated at the
      population level. This study examined the acute appearance of unmetabolized folic
      acid in serum in response to the consumption of some fortified foodstuffs by
      young and elderly volunteers. Subjects on a 5-d regimen of fortified ready-to-eat
      cereal and bread in addition to their normal diet had a threshold intake of 266
      micrograms folic acid per meal at which unaltered folic acid appeared in the
      serum. Subjects given folic acid in either isotonic saline, milk, or white bread
      also had a threshold > 200 micrograms. From patterns of food consumption in the
      United States, the implementation of flour fortification at 1.4 mg/kg is unlikely
      to lead to folic acid appearance in serum, assuming that consumption is spread
      throughout the day. Increasing this level of fortification, however, as has been
      advocated by some agencies, may result in the repeated appearance of folic acid
      in serum over many years, particularly in consumers in nontargeted populations of
      large amounts of fortified foods. The "safe level of intake" of 1 mg folate/d set
      by the US Food and Drug Administration may cause a serum folic acid effect.
      Furthermore, a repeated serum folic acid response is likely to be found in many
      women complying with the advice to take 400 micrograms folic acid/d to prevent
      the occurrence of neural tube defects.

PMID- 9174475
TI  - Serum beta-carotene and vitamin C as biomarkers of vegetable and fruit intakes in
      a community-based sample of French adults.
AB  - Relatively high intakes of vegetables and fruit and relatively low intakes of fat
      are associated with lower rates of heart disease and many types of cancer.
      Biomarkers for vegetable and fruit consumption are most useful when applicable
      across different ages, body weights, diets, and varying patterns of fat intake.
      This study examined two biomarkers, serum concentrations of beta-carotene and
      vitamin C, as a function of anthropometric, dietary, and lifestyle factors in a
      community-based sample of French adults. The interview-based dietary-history
      method was used to assess dietary intakes of 361 males and 476 females aged 18-94
      y resident in the Val-de-Marne district southeast of Paris. Serum beta-carotene
      was quantified by HPLC and vitamin C was measured by using an automated method.
      Serum beta-carotene and vitamin C concentrations were positively associated with
      vegetable and fruit intakes and were negatively linked to the consumption of
      energy, alcohol, and fat. Multiple-regression analyses showed that serum beta
      carotene concentration was predicted by fruit and vegetable intakes but was
      inversely associated with body mass, energy and alcohol intakes, and tobacco use.
      Serum vitamin C concentration was positively associated with fruit consumption
      but was negatively associated with age, body mass, and tobacco use. Serum beta
      carotene and vitamin C concentrations are useful biomarkers of vegetable and
      fruit consumption in the French diet. However, other dietary and lifestyle
      factors also have a significant effect on circulating concentrations of these
      antioxidant micronutrients.

PMID- 9174476
TI  - High dietary calcium intakes reduce zinc absorption and balance in humans.
AB  - Optimal calcium intakes of 37.5 mmol(1500 mg)/d have been proposed for elderly
      people. We investigated the effects of calcium supplementation on zinc absorption
      and balance in 18 relatively healthy, postmenopausal women aged 59-86 y. All
      subjects received a standardized basal diet of typical foods supplying 269 mumol
      (17.6 mg) Zn/d and 22.2 mmol (890 mg) Ca/d during the 36-d study. In two of three
      experimental periods, an additional 11.7 mmol (468 mg) Ca/d as either milk or an
      inorganic calcium phosphate supplement was provided. Net zinc absorption and zinc
      balance were significantly reduced by approximately 2 mg/d during both high
      calcium treatments. In a second study, conducted in a separate group of men and
      women aged 21-69 y, a whole-gut lavage, zinc-absorption test was used to
      investigate the acute effect of a 15-mmol CaCO3 (600 mg Ca) supplement, with and
      without extra zinc, on zinc absorption from a single test meal supplying 111.7
      mumol (7.3 mg) Zn. Zinc absorption was reduced significantly by 50% when the
      calcium supplement was given with the meal. Inclusion of an extra 119.3 mumol
      (7.8 mg) Zn as part of a calcium supplement offset the detrimental effect of
      calcium on zinc absorption. Our findings suggest that high-calcium diets can
      reduce net zinc absorption and balance and may increase the zinc requirement in
      adult humans.

PMID- 9174477
TI  - A compartmental model of zinc metabolism in healthy women using oral and
      intravenous stable isotope tracers.
AB  - A mathematical model of zinc metabolism in six healthy women (average age: 30 +/-
      11 y) was developed by using stable isotopes of zinc. After equilibration on a
      constant diet containing 7.0 mg Zn/d, an oral tracer highly enriched in 67Zn and
      an intravenous tracer highly enriched in 70Zn were administered simultaneously.
      Multiple plasma and 24-h urine samples were collected for the next 7 d with
      complete fecal collections for 11 d. Tracer-trace ratios in plasma, urine, and
      feces were calculated from isotope ratios of 67Zn to 66Zn and 70Zn to 66Zn
      measured by using inductively coupled plasma-mass spectrometry. An a priori
      identifiable model composed of seven compartments was developed to describe the
      kinetics of both tracers as well as that of naturally occurring zinc. The
      parameters of the model were fitted to the data by using the SAAM-CONSAM modeling
      software and were estimated with good precision. Several important, not directly
      measurable zinc variables were estimated (mean +/- SEM) from the model including
      the fractional absorption from the gastrointestinal tract (0.279 +/- 0.043), the
      rates of endogenous secretion (2.79 +/- 0.49 mg/d) and excretion (2.01 +/- 0.35
      mg/d), the fractional turnover rate of the plasma pool (131 +/- 20/d), and the
      sizes (7.2 +/- 1.2 and 77.1 +/- 6.4 mg) and fractional turnover rates (22.3 +/-
      7.1 and 1.49 +/- 0.18/d) of the fast and slow tissue pools equilibrating with the
      plasma, respectively.

PMID- 9174478
TI  - Effect of calcium intake on nonheme-iron absorption from a complete diet.
AB  - Recent studies based on radioiron measurements from single meals have suggested
      that calcium has a strongly inhibitory influence on nonheme-iron absorption. In
      view of evidence that the importance of various dietary enhancers and inhibitors
      of absorption is greatly diminished when assessed by labeling a complete diet,
      the present study evaluated the effect of variations in calcium intake on total
      dietary nonheme-iron absorption. Nonheme-iron absorption was measured in 14
      healthy volunteers during three periods in which the diet was freely chosen or
      modified to decrease or increase dietary calcium intake maximally. The diet was
      labeled during each 5-d period by including with each of the two main meals of
      the day a small bread roll tagged extrinsically with radioiron. Carefully
      maintained dietary records indicated that 69-78% of the daily iron intake was
      labeled by this method. The basal calcium intake of 684 mg/d varied from 280 to
      1281 mg/d when calcium intake was reduced or increased, respectively. Geometric
      mean iron-absorption values of 5.01%, 4.71%, and 5.83% for the three dietary
      periods were not significantly different from one another. No significant
      relation was observed between nonheme-iron absorption and dietary factors known
      to influence iron absorption. We conclude that calcium intake had no significant
      influence on nonheme-iron absorption from a varied diet.

PMID- 9174479
TI  - Dietary caffeine intake and bone status of postmenopausal women.
AB  - Dietary caffeine intake has been suggested as a risk factor for bone loss in
      postmenopausal women. We measured the bone density of both hips and the total
      body in 138 healthy, postmenopausal women aged 55-70 y who had either never used
      hormone replacement therapy (HRT) or had used HRT for < 1 y. In this cross
      sectional study, participants were stratified according to their reported current
      and long-time caffeinated beverage use into one of three groups: low [0-2 cups
      (180 mL, or 6 oz per cup) caffeinated coffee per day], moderate (3-4 cups
      caffeinated coffee per day), or high (> or = 5 cups caffeinated coffee per day).
      Caffeine intake was measured from diet records and by gas chromatography of each
      subject's brewed, caffeinated beverages. No association between caffeine intake
      and any bone measurement was observed. The anthropometric and nutrient intakes of
      the three groups were similar. Compared with caffeine intake based on chemical
      analysis of brewed beverages, 3-d prospective food records and computer-assisted
      analysis overestimated caffeine intake by nearly two-thirds. In conclusion, the
      habitual dietary caffeine intake of this cohort of 138 postmenopausal women
      ranged from 0-1400 mg/d and was not associated with total body or hip bone
      mineral density measurements. This study does not support the notion that
      caffeine is a risk factor for bone loss in healthy postmenopausal women.

PMID- 9174480
TI  - Nutritional influences on bone mineral density: a cross-sectional study in
      premenopausal women.
AB  - The association between current and past dietary intake and bone mineral density
      (BMD) was investigated in 994 healthy premenopausal women aged 45-49 y. BMD was
      measured with dual-energy X-ray absorptiometry (DXA). Dietary intake was assessed
      with a food-frequency questionnaire (FFQ). Energy-adjusted nutrient intakes were
      grouped into quartiles and mean BMD at the lumbar spine (LS), femoral neck (FN),
      femoral trochanter (FT), and femoral Wards (FW) were calculated. With higher
      intakes of zinc, magnesium, potassium, and fiber, LS BMD was significantly higher
      (P < 0.05-0.006), and a significant difference in LS BMD was also found between
      the lowest and highest quartiles for these nutrients and vitamin C intake (P <
      0.05-0.01). These results remained significant after adjustment for important
      confounding factors. LS BMD and FT BMD were lower in women reporting a low intake
      of milk and fruit in early adulthood than in women with a medium or high intake
      (P < 0.01). High, long-term intake of these nutrients may be important to bone
      health, possibly because of their beneficial effect on acid-base balance.

PMID- 9174482
TI  - Refeeding improves muscle performance without normalization of muscle mass and
      oxygen consumption in anorexia nervosa patients.
AB  - The effect of starvation-related malnutrition on muscle performance and on the
      energy cost of exercise remains unknown, as does the timing of improvement by
      refeeding. Indeed, in most diseases that induce malnutrition, muscle dysfunction
      is worsened by an inflammatory process. Thus, physical performance and the energy
      cost of exercise were studied in 15 semistarvated malnourished anorexia nervosa
      (AN) patients during exercise on an ergometric bicycle (3-min steps of 30 W)
      before and after 8, 30, and 45 d of refeeding. Results were compared with those
      of 15 normal-weight healthy subjects matched for age, sex, and physical activity.
      Before refeeding, the workload reached during the exercise was 49% lower in AN
      patients than in control subjects (P < 0.01). It was correlated with body weight,
      fat-free mass, and leg muscle circumference (P < 0.002). The performance improved
      dramatically during refeeding (P < 0.03), reaching normal values after 45 d of
      refeeding, despite fat-free mass and leg muscle circumference values that were
      still 20% lower in AN patients than in control subjects (P < 0.01). At this time,
      the exercise-related VO2 remained unchanged, being approximately 25% lower than
      that of the control subjects when corrected for muscle mass differences (P <
      0.03). In conclusion, in AN patients muscle performance was restored by refeeding
      long before the patients achieved normal nutritional status. The economic cost of
      physical activity for these malnourished patients allows them to maintain a
      relatively high level of physical activity. This relative overactivity has two
      goals in AN: it reinforces anorexia and contributes to the excess of energy
      expenditure needed for weight loss.

PMID- 9174481
TI  - Fiber-supplemented enteral formula slows intestinal transit by intensifying
      inhibitory feedback from the distal gut.
AB  - Because an increase in flow rate accelerates intestinal transit, a reduction in
      the flow rate of formula delivery is recommended frequently for treatment of
      diarrhea that develops during enteral feeding. Because intestinal transit is
      slowed by nutrient-triggered inhibitory feedback, the rate of intestinal transit
      during enteral feeding may depend on a balance between the accelerating effect of
      flow and the inhibiting effect of the nutrient load. The addition of fiber to a
      formula may alter this balance. By delaying absorption of nutrients, fiber may
      extend the length of small intestine exposed to nutrients and thereby trigger
      more intense inhibitory feedback. To determine whether the addition of fiber
      favors nutrient-triggered inhibition over flow-driven acceleration, we studied
      intestinal transit after perfusion of a low-residue enteral formula compared with
      a fiber-supplemented formula at two perfusion rates (50 or 100 mL/h for 2 h) into
      the duodenum of dogs each with both a duodenal and midgut fistula. With the low
      residue formula, intestinal transit accelerated when the flow rate increased from
      50 to 100 mL/h (P < 0.05). With the fiber-supplemented formula, however,
      intestinal transit was inhibited regardless of the flow rate. To determine
      whether the fiber-supplemented formula inhibited intestinal transit by displacing
      nutrients distally, we compared intestinal transit when the two formulas,
      delivered at 100 mL/h, were diverted completely at the midgut fistula. Intestinal
      transit of the fiber-supplemented formula increased by 400%, eliminating the
      difference in intestinal transit speed between the two formulas. We concluded
      that the fiber-supplemented formula slowed intestinal transit by intensifying
      inhibitory feedback from the distal gut.

PMID- 9174483
TI  - Factors influencing malnutrition in children waiting for liver transplants.
AB  - Nutrition deficiencies are common in children with chronic liver disease. To
      determine whether age, hepatic dysfunction, or energy intake influences this
      malnutrition, we evaluated the nutritional status of 49 children aged 2.5 mo to
      13 y (mean: 35 mo; median: 12 mo). The children were divided into two groups
      according to age: group 1-29 patients aged < or = 1 y (mean: 7 mo; median: 7 mo);
      and group 2-20 patients > 1 y (mean: 75 mo; median: 59 mo). Hepatic dysfunction
      was defined according to the Malatack criteria. Seventy-two-hour dietary intakes
      were recorded by a nutritionist. Nutritional status was assessed by
      anthropometric measures when the patients were enrolled on the waiting list for
      liver transplants. We evaluated the following indexes: weight, height, fat body
      mass, and lean body mass on the basis of height-age (age at which height reached
      50th Italian height percentile). Mean height Z scores were low in both groups,
      but the difference was not significant. Mean weight Z scores and mean percentages
      of fat body mass were significantly lower (P < 0.001) in group 1 than in group 2
      patients. In group 2, lean body mass and fat body mass were significantly lower
      (P < 0.05) in patients with moderate-to-severe hepatic failure than in patients
      with mild hepatic dysfunction. The mean energy intake was in the range of the
      recommended daily allowances for age but was insufficient for both groups of
      patients. The evidence of significant acute and chronic malnutrition confirmed
      the need for nutritional support, especially for younger and older children with
      moderate-to-severe hepatic dysfunction. We emphasize the necessity of accurate
      assessment of nutritional status by simple anthropometric measurements to be sure
      of the effects and adequacy of the nutritional intervention.

PMID- 9174484
TI  - Plasma vitamin C concentrations in patients with cystic fibrosis: evidence of
      associations with lung inflammation.
AB  - Vitamin C status and possible associations with the disease process in cystic
      fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in
      patients from two different mid-European populations (Swiss, n = 62; Austrian, n
      = 60) taking no or low-dose vitamin C from multivitamin supplements did not
      differ from each other or from control subjects (n = 34). Vitamin C
      concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12
      mo, patients had the highest plasma vitamin C concentrations in February and the
      lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by
      increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha
      concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta
      carotene for 12 mo vitamin C concentrations did not change. They correlated
      inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P
      = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = 
      0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes
      (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L,
      all indexes of inflammation were relatively high, whereas those with
      concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly
      lower values. These results are consistent with the hypothesis that by scavenging
      oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of
      activation of alveolar macrophages and neutrophils, release of proinflammatory
      cytokines and oxygen free radicals, and inactivation of antiproteases.

PMID- 9174485
TI  - Extended use of foods modified in fat and sugar content: nutritional implications
      in a free-living female population.
AB  - The nutritional implications of the consumption of reduced-fat and reduced-sugar
      foods were assessed in nonobese, free-living female consumers in a 10-wk
      intervention trial. Subjects in control (C; n = 13), reduced-fat (RF; n = 17),
      and reduced-sugar (RS; n = 19) groups, all initially nonusers of reduced-fat and
      reduced-sugar products, kept 4-d food-intake records to establish energy and
      macronutrient intakes at baseline and at 2,4,7, and 10 wk. Groups RF and RS were
      instructed to use reduced-fat and reduced-sugar foods, respectively, ad libitum
      in place of habitually consumed foods with traditional composition, whereas group
      C was to maintain their usual diet. All foods were purchased by subjects in
      normal retail outlets and consumed at home. Analyses revealed no main or
      interactive effect of group on reported energy intake. RF subjects reduced their
      reported fat intake during the study (P = 0.017) compared with RS and C subjects,
      and RS subjects reduced their reported sucrose intake compared with RF and C
      subjects (P = 0.049). Group differences in total sugar intake were not
      significantly different. All groups reported a small but significant increase in
      reported protein intake during the study, whereas there were no significant
      effects on percentage energy from total carbohydrate. Body weights did not change
      significantly in any group over the study period. These results indicate that, as
      a single dietary strategy, casual use of macronutrient-substituted foods by
      consumers under normal eating conditions can significantly influence the
      macronutrient composition of the diet, but has little net effect on total energy
      intake or body weight status.

PMID- 9174486
TI  - N-3 fatty acids do not lead to an increased diabetic risk in patients with
      hyperlipidemia and abnormal glucose tolerance. Italian Fish Oil Multicenter
      Study.
AB  - A multicenter, randomized, double-blind, place-bo-controlled study evaluated the
      possible worsening of glycemic control after a moderate daily intake of n-3 fatty
      acid ethyl esters in patients with hypertriglyceridemia with and without glucose
      intolerance or diabetes. A total of 935 patients of both sexes in 63 Italian
      clinical centers were selected; 55% had either impaired glucose tolerance or non
      insulin-dependent diabetes mellitus (NIDDM). They received for 2 mo either 1 g n
      3 ethyl esters three times a day or a corresponding placebo, followed by 4 mo of
      either 1 g n-3 ethyl esters twice a day or placebo. In addition to the complete
      lipid and lipoprotein evaluation, patients with impaired glucose tolerance also
      underwent an oral-glucose-tolerance test; in patients with NIDDM, serum insulin
      and glycated hemoglobin (Hb A1c) concentrations were determined. Plasma
      triacylglycerol concentrations decreased significantly, up to 21.53% at 6 mo
      compared with baseline (decreased 15% compared with placebo), with a tendency
      toward a progressive reduction with time. There was no evidence for a different
      response in patients with either NIDDM or impaired glucose tolerance. Among NIDDM
      patients, the triacylglycerol reduction was greater in those with high-density
      lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major
      glycemic indexes: fasting glucose, Hb A1c, insulinemia, and oral glucose
      tolerance in patients with impaired glucose tolerance or NIDDM after treatment
      with n-3 ethyl esters. Treatment with a moderate daily dose of n-3 ethyl esters
      over a prolonged period of time significantly reduced triacylglycerol
      concentrations without any worsening of glucose tolerance in patients with
      hypertriglyceridemia with and without impaired glycemic regulation.

PMID- 9174487
TI  - Heart disease risk-factor status and dietary changes in the Cretan population
      over the past 30 y: the Seven Countries Study.
AB  - A follow-up study was conducted to identify the heart disease risk-factor status
      and dietary changes of surviving elderly subjects in Crete who took part in the
      Seven Countries Study in 1960. In 1991, data were obtained from 245 of the 686
      original male participants (169 of the original 40-49-y age group and 76 men 50
      59 y age group). In 1991, the men were 70-79 and 80-89 y old. There was a
      significant (11.5%) increase in serum total cholesterol concentrations between
      1960 and 1991. Body mass index and systolic and diastolic blood pressures also
      increased significantly, and all age groups were characterized by central
      obesity. A representative subsample of 21 men took part in a 3-d weighed food
      record study. Dietary data indicated increases in the intake of saturated fat and
      decreases in monounsaturated fat over the 30-y period. Comparison with a 1962
      representative Cretan sample indicated a significantly increased concentration of
      adipose palmitic acid (16:0) in our surviving sample. The observed changes
      occurred during a period when many developed countries were observing a decline
      in most heart disease risk factors.

PMID- 9174488
TI  - Visceral fat mass in childhood: a potential early marker for increased risk of
      cardiovascular disease.

PMID- 9174489
TI  - Let's increase folic acid fortification and include vitamin B-12.

PMID- 9174490
TI  - Ascorbic acid: hype, hoax, or healer?

PMID- 9174491
TI  - Diet and serum lipid concentrations: where are we?

PMID- 9174492
TI  - Biological variation of transferrin receptor and ferritin.

PMID- 9174493
TI  - Bioavailability of calcium supplements.

PMID- 9174494
TI  - Jeng et al paper a disappointment.

PMID- 9174495
TI  - Destroying immune homeostasis in normal adults with antioxidant supplements.

PMID- 9174496
TI  - Morbidity in family medicine: the potential for individual nutritional
      counseling, an analysis from the Nijmegen Continuous Morbidity Registration.
AB  - Nutritional counseling is a common primary care intervention but few empirical
      data are available. This study analyzed morbidity in family medicine practices
      and the relevance of nutritional counseling. Morbidity data from the Nijmegen
      University family medicine Continuous Morbidity Registration were studied. Since
      1967 four practices (seven family physicians) have recorded all new episodes of
      illness. Physicians were trained and supervised monthly in their coding and
      classification of morbidity with diagnostic criteria. Two experienced family
      physicians assessed the nutrition sensitivity of all 400 diagnostic rubrics of
      the classification list. Incidence and prevalence of all morbidity and of
      nutrition-sensitive morbidity were calculated. The most common (chronic) diseases
      in family practice were a mixture of diseases of organ and body systems:
      hypertension, obesity, cardiovascular disease, chronic arthritis, asthma, chronic
      obstructive pulmonary disease, eczema, and diabetes mellitus. The prevalence of
      these diseases gradually increased in the past decade. Forty-eight diagnostic
      rubrics were considered to be nutrition sensitive, accounting for 16.5% of
      diagnoses recorded. Their prevalence also increased in the past decade. The
      survey supports the importance of nutrition-related interventions in family
      medicine but underlines that these interventions are directed at a variety of
      illnesses and patient groups. Common nutritional intervention techniques that can
      be applied in the personal care of patients in the context of their family life
      should be developed.

PMID- 9174497
TI  - Effectiveness of dietary intervention in general practice.
AB  - The scope for dietary intervention in general practice is substantial. The three
      most prevalent conditions for which general practitioners are likely to give
      dietary advice are hypertension, functional digestive disorders, and ischemic
      heart disease. As well as clinical diseases, risk factors such as raised plasma
      cholesterol concentrations also provide opportunities for dietary intervention.
      But resources are limited. If a general practitioner or nurse spends 5 min of a
      10-min consultation on dietary advice, there is 5 min less to spend on the rest
      of the consultation. Research studies in general practice show that small changes
      in plasma cholesterol concentrations can be achieved by dietary interventions.
      Intensive intervention can also influence salt intake to a small extent. However,
      the most important, potentially cost-effective roles for the general practitioner
      in health promotion are the legitimization and reinforcement of public health
      information by brief advice and the distribution of written material. Secondary
      and tertiary prevention is a priority in general practice and may entail use of
      drugs, but drugs are not a desirable solution for the unhealthy diets of healthy
      people.

PMID- 9174498
TI  - Nutrition and general practice: an Australian perspective.
AB  - Australia has a government-subsidized, private medical system in which general
      practitioners (GPs) form the core component of primary care. There are
      approximately 20,000 active GPs and 80% of the population consults a GP each
      year. A new vocational register of GPs has been set up that requires training in
      general practice, followed by formal continuing education. I briefly review
      sources of information about Australian GPs' practices and knowledge of and
      attitudes toward nutrition. About 15-17% of GPs say they have a special interest
      in nutrition (20% of female GPs and 13% of male GPs). The main conditions for
      which advice is given are heart disease, hyperlipidemia, obesity, and diabetes.
      The extent of nutrition counseling by GPs is considerably less than might be
      expected from the strength of their statements about the importance of nutrition
      and long-term health. Obstacles to nutrition counseling are lack of time, lack of
      confidence, and inadequate nutrition knowledge, the last documented by objective
      testing. GPs express interest in learning more about nutrition (which may be
      partly driven by consumer pressure) but there is still little coherent teaching
      on the subject, specifically tailored for GPs. When asked their preferences for
      nutrition education, GPs tend to prefer educational material (such as diet
      charts) to give to patients.

PMID- 9174499
TI  - Challenges to prevention in Dutch general practice.
AB  - In the Netherlands the general practitioner (GP) plays an important role in
      prevention. Every Dutch citizen has to be registered with one GP and GPs know
      their patients well. Face-to-face contact is a relatively effective means of
      influencing behavior; if preventive advice is related to a patient's state of
      health, compliance may be stimulated. However, Dutch GPs have shown reluctance
      toward preventive work. Curing rather than preventing disease is emphasized in
      medical school. Many GPs doubt that they are entitled to interfere with a
      patients' lifestyle unless asked. Some GPs are aware of their limited knowledge
      of nutrition. Preventive work requires some reorganization of medical practice
      and can lead to an increased workload, without financial compensation. Then there
      is the "prevention paradox": preventive actions that have a demonstrable effect
      on the whole population bring only small benefits for individuals. Since 1989 the
      Dutch College of General Practitioners has published 60 standards for general
      practice. Several of these include advice on lifestyle and diet, eg, for non
      insulin-dependent diabetes mellitus, hypertension, hypercholesterolemia, peptic
      ulcer, and heart failure. Prevention work in general practice must use only
      interventions proved to be effective and they must be feasible in the context of
      general practice. A trial collaboration of 118 GPs and 5 public health
      authorities between 1988 and 1990 for screening and lifestyle management of
      hypertension was a limited success. It brought to light the practical problems of
      this type of work in general practice. Present government priorities for GP
      public health collaboration are influenza vaccination and cervical screening.

PMID- 9174500
TI  - Long-term effect of nutritional counseling: a study in family medicine.
AB  - This paper reports research using data in the Nijmegen Family Practice Monitoring
      Project. One part of the research is follow-up, after 17 y, of a 1977 trial of
      dietary advice for patients with hypertension or a family history of premature
      cardiovascular disease. In the intervention group, 840 patients were given health
      education every 2 mo by trained practice nurses for 1 y. There were 497 patients
      with similar coronary risk factors in the control group, who received usual care.
      One year after the intervention a significant decrease was found (and published)
      in serum cholesterol concentrations and blood pressure in the intervention group.
      By the time of the 1995 reexaminations, however, there were no differences in
      coronary risk factors between the two groups. Blood pressures had come down, more
      so in the control group, and the percentage of smokers had decreased equally in
      both groups. There were no significant differences in intake of dietary fat or in
      type of fat. The lack of difference was still found when the groups were divided
      into those with serum cholesterol concentrations > and < 6.5 mmol/L. A second
      part of the research was to investigate in 1995 the relation between patients'
      stage of change of fat intake and their dietary intake. It was found that those
      in stage 5 (sustaining desired changes in behavior) had the lowest saturated fat
      intake. Since 1977 both groups have been treated equally if hypertension was
      diagnosed. The two groups were not managed differently with regard to dietary
      advice after 1977.

PMID- 9174501
TI  - Advice on healthy food as given by Flemish general practitioners.
AB  - I report on a search of international and Belgian literature for publications
      about nutritional work in general practice. I found little information. Reports
      on four local actions were found, focusing on cardiovascular disease, diabetes,
      or increasing fiber intake. Universities should be stimulated to pay more time
      and attention both to knowledge about foods and to training on how to give
      nutritional advice. The lesson on healthy food developed with dietitians for the
      Flemish Institute for Continued Medical Education needs more support.

PMID- 9174502
TI  - Handling nutritional advice in general practice in Norway.
AB  - General practitioners (GPs) in Norway are in a unique position to influence their
      patients' lifestyles during consultations. The specialty of family medicine has
      been recognized in Norway since 1985. In continuing medical education, nutrition
      issues are integrated with the discussion of relevant diseases. The first book on
      health education for Norwegian general practice (1990) contains a set of general
      dietary guidelines. GPs are informed of the results of the National Health
      Screening Service, which measures blood pressure and serum lipids and records
      smoking habits. Serum cholesterol concentrations and coronary artery disease
      mortality are declining. GPs have been involved in this achievement, although
      they were found in 1988 to set more conservative cutoffs of serum cholesterol
      concentrations for dietary advice than an expert committee. GPs have been
      directly involved in preparing the latest cholesterol guidelines. In 1994
      Norwegian GP organizations started a project of quality indicators in general
      practice (SATS). Of the four conditions that are themes for the first project,
      treatment of diabetes mellitus has a major nutritional aspect.

PMID- 9174503
TI  - Nutritional counseling in German general practices: a holistic approach.
AB  - There is consensus among all German health professionals, including primary care
      physicians, that a holistic approach to healthy living begins with good
      nutrition. In northern Baden, 2100 general practitioners and internists were
      asked about their nutritional attitudes and preventive counseling in daily
      practice. Of responding physicians, 75% attributed great importance to prevention
      in general and 92% to nutrition in particular, 65% were providing special
      programs such as "How to treat diabetes by myself" or "Reducing hypertension by
      losing weight." Together with the highest German Committee of Physicians, the
      Lectures in General Medicine of the University of Heidelberg held a meeting on
      nutritional counseling in general practice. The 23 participants collected
      statements and information on the topics of education and counseling, support for
      improved teaching, and knowledge about nutritional attitudes and food. The
      Heidelberg agreements are as follows: 1) good nutritional counseling can reduce
      morbidity of important diseases, 2) nutritional counseling must be improved in
      general practice, 3) diagnosis-related written cases for systematic counseling
      should be available, 4) family doctors should cooperate with nutritionists, and
      5) for quality assurance, the three-level strategy of primary care should be
      recommended because of the positive results of the Bruchsal-Oestringen program
      (reduction of obesity and hypercholesterolemia). General practice can become a
      place of improved nutritional counseling and education if the use of programs
      proven to be successful, additional exercise-based community approaches, and
      quality assurance can be facilitated. The outcome of practice-based studies may
      encourage primary care physicians to spend more time and training on nutrition
      guidance.

PMID- 9174504
TI  - Nutrition in general practice in Italy.
AB  - Since the early 1950s the health promoting qualities of the Mediterranean diet
      (characterized by low intakes of total and saturated fat and high intakes of
      fiber and complex carbohydrates) have been acknowledged. Unfortunately, this
      dietary pattern, effective in lowering the risk of coronary artery disease as
      well as oxidative stress and carcinogenesis, is widespread only in the southern
      part of Italy, whereas the eating style and morbidity pattern in northern Italy
      are similar to those in northern Europe. Moreover, trends in eating behaviors in
      southern Italy are at risk of impairing the comparative advantage given by the
      Mediterranean diet. The current eating profile in northern Italy and the trend in
      southern Italy are therefore a suitable field for educational interventions by
      general practitioners (GPs) to preserve and promote healthier dietary patterns.
      Nutrition training of GPs does not yet appear sufficient to enable them to tackle
      this need. The undergraduate curriculum used to include (and no longer does) only
      an optional course in basic nutrition; little more teaching is added during
      vocational training. In Piedmont, a north-western region around Turin, two four
      hour seminars for vocational trainees deal with the topics of basic nutrition in
      children, adolescents, and adults; malnutrition in the elderly; and diet
      treatment of chronic renal failure. Continuing medical education covers the same
      topics and a further module deals with diet in the control of diabetes. An effort
      is needed in the nutritional training of Italian GPs to enable them to give to
      their patients more than merely commonsense advice.

PMID- 9174505
TI  - Nutritional factors in Dutch family medicine: an inventory.
AB  - By 1995 the Dutch College of General Practitioners (Nederlands Huisartsen
      Genootschap, or NHG) had developed 53 standards that spell out the preferred
      policy of detection, treatment, and control of different clinical conditions in
      general practice. In 35 of these NHG standards nutrition is of some significance.
      Each of them is briefly discussed. Eighteen conditions, not yet in the set of
      standards, have specific pathologies with nutritional factors. Each is briefly
      explained. Last, 17 groups of diseases or background conditions are discussed in
      which nutritional advice is especially important. The science of nutrition ought
      to have an established place in the vocational training of general practitioners.
      To help general practitioners give adequate nutritional advice, they should have
      regular consultations with dietitians.

PMID- 9174506
TI  - Consumers' expectations about nutrition guidance: the importance of primary care
      physicians.
AB  - To clarify the role of the primary care physician (PCP) in providing nutrition
      information to the public, we investigated in a random sample of Dutch consumers
      their referral to 11 nutrition information sources including the PCP, their
      perceived expertise of these sources, their interest in nutrition information,
      and their nutritional attitudes and beliefs. Factor analysis over these 11
      sources of nutrition information resulted in two factors: noncommercial sources
      (alpha = 0.70) and commercial sources (alpha = 0.78). Respondents' referral to
      and perceived expertise on a five-point scale of noncommercial sources was higher
      than for commercial sources [respectively, 54% compared with 21%, P < 0.0001, and
      3.9 +/- 0.6 compared with 2.7 +/- 0.6 (mean +/- SD), P < 0.01]. The individual
      Spearman correlation coefficient between referral scores and perceived expertise
      was p = 0.35 +/- 0.36 (mean +/- SD). For most sources, referral to that source
      was dependent on a higher interest in information about a healthy diet and on
      perceived expertise of the source. There were three leading noncommercial
      sources: the PCP, the dietitian, and the Netherlands Food and Nutrition Education
      Bureau (FNEB). Careful analysis revealed that because of their high referral
      scores, high perceived expertise, and reach to nearly all segments of the
      population, PCPs are in a unique position compared with dietitians and the FNEB.

PMID- 9174507
TI  - Consumer involvement in nutritional issues: the role of information.
AB  - Finding a strategy to improve-diets is a concern of many politicians and health
      promoters. Distribution of information is one strategy, but seems to be
      relatively unsuccessful. There is public awareness of the role of diet in health,
      but this awareness has not led to sufficiently improved eating habits. What
      people buy and eat depends not only on individual but also on social, cultural,
      economic, and environmental factors. These factors are interrelated and food
      choice is a complex process, which explains why information supply on its own is
      insufficient as a strategy to promote healthy eating. Public health professionals
      in eight European cities therefore decided to use the health promotion approach
      as an alternative strategy to promote healthy eating. The essence of this
      approach is community action in which participation and multisectoral
      collaboration are key elements. Each of the sectors, such as consumers,
      supermarket managers, social workers, school teachers, restaurant keepers, and
      health workers, try to undertake actions that support positive individual
      behavior change. This so-called SUPER project has been running for 5 y and
      results to date are promising. Nutrition is emphasized in several places in the
      community. In this way people are involved in the process and become interested
      in and curious about healthy eating. Experiences of working with this strategy
      and opportunities for primary care physicians to apply this approach are
      presented.

PMID- 9174508
TI  - Food and nutrition: attitudes, beliefs, and knowledge in the United Kingdom.
AB  - In a study of 1700 members of the UK general public in 1992 in which face-to-face
      interviews were conducted, factors thought important in a healthy diet were (in
      descending order) more fiber, less sugar, less fat, less salt, and more starchy
      foods. Of common nutritional terms there was most confidence in explaining the
      meaning of fiber and least in the meaning of monounsaturated fatty acids. Most
      nutritional information came from the media but the credibility of this
      information was low. Fifty-three percent said that a conversation with their
      general practitioner (GP) was a source of advice they trusted. In a survey of 150
      GPs and 50 practice nurses in 1992, lack of confidence was found to be common
      concerning the meaning of several nutritional terms, especially extrinsic sugars,
      NSP (nonstarch polysaccharide), and trans fatty acids. GPs were confident they
      could explain the link between diet and heart disease but were not sure about the
      value of starch in the diet. Both GPs and practice nurses were dissatisfied with
      their training in nutrition, both before and after registration. General practice
      staff thought that personal ill health was the most important motivator for
      dietary change among their patients. They thought that apathy and dietary
      conservatism were the most common barriers to people changing their diet.
      However, the public positioned lack of knowledge as the biggest obstacle. Surveys
      reported here showed that people's knowledge of sources of fat, calcium, and iron
      is often unreliable.

PMID- 9174509
TI  - Information sources and strategies of nutrition guidance used by primary care
      physicians.
AB  - We studied the nutrition information seeking behavior of primary care physicians
      (PCPs) and also PCPs' implementation of different strategies of nutrition
      guidance of patients. This was done by means of a questionnaire mailed to a
      nationwide random sample of 1000 PCPs in the Netherlands. The net response rate
      was 64%. The two most important nutrition information sources for PCPs were a
      dietitian (72% of respondents) and the literature (34% of respondents). Eighty
      five percent of PCPs reported that they were actively involved in seeking
      nutrition information. For nutrition education of patients, PCPs gave personal
      information to patients, referred patients to a dietitian, and made publications
      available in the surgery. As preferred methods of obtaining nutrition information
      themselves, PCPs listed scientific journals, postgraduate nutrition education,
      congresses and study days, and publications. Determinants of nutrition
      information seeking behavior of PCPs as well as their implementation of different
      strategies of patient nutrition education were identified and discussed. PCPs
      were familiar with the body mass index, which is encouraging because treatment of
      overweight and obesity starts with a valid assessment. The findings in this study
      lead to a prudent positive conclusion about PCPs and nutrition information in
      practice. From this study and others it can be concluded that there are growing
      opportunities, challenges, and tools for PCPs to become more actively involved in
      nutrition guidance of patients.

PMID- 9174511
TI  - Nutrition practices of family physicians after education by a physician nutrition
      specialist.
AB  - Although nutrition is an important part of medical care, nutrition education is
      not provided in most training programs for physicians in the United States,
      resulting in limited nutrition knowledge among physicians and limited nutritional
      care of patients. A nutrition education program was provided by a physician
      nutrition specialist in a family practice residency program. For 6 mo, the
      nutrition specialist provided the family physicians with recommendations for
      nutritional care for their patients. The effects of the education program on
      residents' and faculty physicians' nutrition knowledge and nutritional patient
      care, patients' perceptions of the importance of nutrition, and physicians'
      dietary patterns were determined by pre- and post-intervention nutrition exams
      for physicians and patients, patient questionnaires about attitudes toward
      nutrition, chart reviews, and physicians' diet records. The nutrition education
      program resulted in an increase in physicians' nutrition knowledge scores (P <
      0.01) and an increase in the frequency with which physicians discussed nutrition
      and recommended diets for their patients (P < 0.05). This suggests that nutrition
      education by a physician nutrition specialist within a family practice residency
      program can be effective in increasing nutritional care provided to patients.

PMID- 9174510
TI  - Importance of diet and sex in prevention of coronary artery disease, cancer,
      osteoporosis, and overweight or underweight: a study of attitudes and practices
      of Danish primary care physicians.
AB  - General practitioners (GPs) in Denmark (n = 374) answered a questionnaire on
      attitudes toward including information on diet and sex in the prevention of
      coronary artery disease, cancers, osteoporosis, and weight problems. Risk factors
      for disease were ranked as follows: smoking, alcohol, stress, diet, physical
      exercise, heredity, and hygiene. Patients' lack of motivation, insufficient time
      for each patient, and inadequate knowledge about nutrition were listed by GPs as
      barriers to dietary counseling. GPs stated that the sex of the patient was
      important only for counseling on osteoporosis. Lack of time and insufficient
      knowledge were perceived as barriers to including sex-specific issues in
      prevention. One-half of the GPs were questioned about the issue of prevention on
      the basis of female case stories and the other half on the basis of male case
      stories with identical wording. Responses to the case stories indicated that GPs
      would give dietary guidance and recommend loss of weight to slightly overweight
      male patients to a much greater degree than to overweight female patients for
      prevention of coronary artery disease, give dietary counseling and recommend loss
      of weight and exercise to female patients more than to male patients for
      prevention of cancers, recommend a supplement of calcium and vitamin D for
      prevention of osteoporosis to female patients, and recommend weight gain and
      discuss psychosocial issues more with underweight female patients than with
      underweight male patients. Female GPs included measures of prevention such as
      dietary counseling, exercise prescription, dietary supplement prescription, and
      discussion of psychosocial issues to a greater extent than did male GPs.

PMID- 9174512
TI  - Primary care physicians and clinical nutrition: can good medical nutrition care
      be offered without well-trained physicians in the area?
AB  - The senior author, immediate past president of the IUNS (International Union of
      Nutritional Sciences), makes the case here that the standard, recognition, and
      efficiency of nutritional work in primary care are linked to the status of
      clinical nutrition in teaching hospitals. There should be opportunities for
      physicians interested in clinical nutrition to be trained and have a profile
      similar to other clinical specialists. The clinical nutrition group in the
      Department of Internal Medicine at the teaching hospital of the Medical School of
      Ribeirao Preto, Brazil, is an example of a functioning clinical unit. Statistics
      are presented comparing patient numbers for the clinical nutrition group at
      Ribeirao Preto with other clinical services (cardiology, nephrology, and
      geriatrics). Clinical nutrition has its own clinical methodology and technology.
      When clinical nutrition is visible and recognized in medical schools, skills in
      nutrition will extend beyond hospital boundaries and become useful in the primary
      care of patients at the community level.

PMID- 9174513
TI  - Media choice in nutrition education of general practitioners.
AB  - In the traditional model of communicating information, a general practitioner
      receives information from his or her teacher (when they choose to give it) and
      from print media (books and journals) and in turn can pass on the information
      didactically to patients (whether they asked for it or not). The arrival and
      development of new electronic media are changing the system and the
      possibilities. Patients now have access to more information independently (some
      of it correct, some misleading). GPs cannot trust their own solid body of
      knowledge any longer. To keep up with new and rising expectations they must
      become professional information seekers. New media will give opportunities for
      GPs to look for information by electronic means at the time that they need it,
      eg, through on-line connections with databases or through use of CD-roms. The
      role of journals will change from simply providing detailed data; journals can
      concentrate on the questions behind the questions.

PMID- 9174514
TI  - Review of nutritional attitudes and counseling practices of primary care
      physicians.
AB  - I review major issues covered at the International Workshop on Nutritional
      Attitudes and Practices of Primary Care Physicians and synthesize some of the key
      findings presented at this workshop and found in the scientific literature. After
      presenting the rationale for managing nutritional problems in primary health
      care, I discuss the extent of both practice and international differences. Next,
      the determinants of attitudes and practices, in terms of both individual and
      system-level factors, are examined. Various types of interventions and the
      available data regarding their efficacy are reviewed. I then raise a variety of
      considerations regarding research methodologies and describe work in progress.
      Finally, suggestions are advanced regarding opportunities for increasing and
      improving physicians efforts to manage nutritional concerns and for pursuing
      promising future directions for better health through nutrition.

PMID- 9174515
TI  - Radiographic detection of gravel in soft tissue.
AB  - STUDY OBJECTIVE: We sought to quantify the detectable size of varying
      compositions of gravel using a cadaveric chicken leg wound model and standard
      plain-film two-view radiographs. METHODS: We conducted a randomized, blinded,
      descriptive study with the assistance of faculty from the emergency medicine and
      radiology residency programs of a private urban teaching hospital. A standardized
      wound was created in each of 160 cadaver chicken legs. Zero, one, or two pieces
      of gravel of four differing compositions, ranging in size from .25 to 2.0 mm,
      were inserted into the wounds as determined with computer-generated
      randomization. The legs were then radiographically imaged (anteroposterior and
      lateral views). Three faculty physicians independently interpreted the
      radiographs to determine the number of foreign bodies and rated the ease of
      visibility. We calculated sensitivity, specificity, and interobserver
      reliability. RESULTS: The accuracy with which gravel was detected ranged from an
      average of 97.7% for 2-mm and 1-mm particles to less than 75% for .5-mm and .25
      mm particles. Visibility ratings were also lower for particles in the smaller
      ranges. Sensitivity was greater for the emergency physicians than for the
      radiologists, but their specificity was lower. Salt-and-pepper gravel was the
      most easily identified foreign body. CONCLUSION: In this wound model, gravel
      particles of less than 1 mm were not accurately identified.

PMID- 9174516
TI  - Ultrasound-guided retrieval of small foreign objects in subcutaneous tissue.
AB  - STUDY OBJECTIVE: To identify the physical properties of the materials most easily
      located in subcutaneous tissue through the use of conventional ultrasound.
      METHODS: High-resolution real-time sonography was performed by a credentialed
      sonographer on a chicken breast impregnated with five objects-a metal paper clip,
      a wooden toothpick, a plastic coffee stirrer, a shard of glass, and an 18-gauge
      needle. Transducer frequencies ranging from 3.5 to 7.5 MHz with linear,
      curvilinear, and sector-scanning formats were used. All images were interpreted
      by a staff attending radiologist with other study authors present. The chicken
      breast was then subjected to radiography for comparison. RESULTS: Wood yielded
      the strongest acoustic shadow; plastic had the next-best acoustic shadowing. The
      7.5-MHz probe yielded its best resolution at shallow depths, whereas the 5-MHz
      probe was best at greater depths. CONCLUSION: We conclude that ultrasonography is
      an excellent technique for the localization and retrieval of nonradiopaque
      foreign objects in the superficial subcutaneous tissue. It should be given
      consideration for use in the removal of nonradiopaque superficial foreign objects
      when conventional radiographic techniques are not effective.

PMID- 9174517
TI  - Urine ketone dip test as a screen for ketonemia in diabetic ketoacidosis and
      ketosis in the emergency department.
AB  - STUDY OBJECTIVE: To determine the sensitivity of the urine ketone dip test (UKDT)
      for the detection of ketonemia in patients with diabetic ketoacidosis (DKA) and
      diabetic ketosis (DK) in the ED. METHODS: We conducted a retrospective chart
      review in the ED of an urban, university-affiliated county teaching hospital. The
      study population comprised patients seen in the ED during 1994 and 1995 with a
      discharge diagnosis of DKA or DK and underwent urinalysis within 4 hours of the
      initial serum electrolyte and ketone determinations. We calculated test
      sensitivity, along with 95% confidence intervals (CIs). RESULTS: One hundred
      forty-eight patients with 223 occurrences diagnosed as DKA or DK were seen in the
      ED during the study period. One hundred fourteen patients with 146 occurrences of
      DKA or DK met all inclusion criteria; these patients made up the study group.
      There were 99 cases of DKA and 47 cases of DK. The sensitivity of the UKDT for
      the detection of ketonemia in all patients with DKA or DK was 97% (95% CI, 94% to
      99%). In the subgroup of patients with DKA, the sensitivity of the UK was 97%
      (95% CI, 92% to 99%). For patients with DK, the sensitivity of the UK was 98%
      (95% CI, 89% to 99%). CONCLUSION: The UKDT is highly sensitive for the presence
      of serum ketones in patients with DKA and DK. Prospective study is suggested to
      determine the specificity of the UKDT in this application and to validate its use
      as a screening tool for the detection of ketonemia in DKA and DK.

PMID- 9174518
TI  - Estimated use of a pediatric emergency department observation unit.
AB  - STUDY OBJECTIVE: To estimate the use of a pediatric ED observation unit,
      including the number of anticipated admissions per 10,000 pediatric ED visits per
      year and the distribution of those admissions by age group, by month, and by time
      of day. METHODS: Hospital and ED computer records on all ED patients younger than
      18 years who were seen during a 2-year period were abstracted for diagnostic,
      demographic, and time-flow data. We retrospectively reviewed the charts of
      patients admitted to the hospital and discharged within 24 hours to determine
      whether discharge in less than 24 hours could have been anticipated and whether
      the patient could have been cared for in a pediatric ED observation unit. To
      refine the estimate, we also reviewed the ICD-9 discharge diagnoses of patients
      who were not admitted to the hospital but spent more than 6 hours in the
      pediatric ED. RESULTS: Of 29,667 pediatric ED visits in a 2-year period, 2,940
      (10%) resulted in admission. Of 626 patients discharged in less than 24 hours,
      only 410 met the anticipation and pediatric ED observation unit level of care
      criteria. Patients younger than 4 years represented 43% of potential observation
      unit patients; those aged 16 and 17 years represented 15%. Potential use of an
      observation unit varied throughout the year. Admission occurred between 3 and
      11:59 PM in 60% of the patients. Only 20% of the 176 patients who were not
      admitted to the hospital but spent more than 6 hours in the pediatric ED were
      estimated to be candidates for a pediatric ED observation unit. CONCLUSION: On
      the basis of these data, approximately 150 patients per 10,000 each year who
      visit the University of Virginia pediatric ED would be likely to use an
      observation unit. Staffing and facility use would be seasonally uneven and would
      be required during the busiest part of the day. Furthermore, even in a pediatric
      ED large enough to admit 365 pediatric ED observation unit patients each year,
      random daily variation in demand means that a single bed would be inadequate 25%
      of the time and empty 37% of the time. Optimal use of even a single-bed pediatric
      ED observation unit would not occur until pediatric ED census exceeded 30,000 to
      40,000 visits annually.

PMID- 9174519
TI  - Children and adults in cardiopulmonary arrest: are advanced life support
      guidelines followed in the prehospital setting?
AB  - STUDY OBJECTIVE: To compare the proportions of children and adults in whom
      advanced life support (ALS) guidelines for prehospital management of
      cardiopulmonary arrest. METHODS: We conducted a retrospective cross-sectional
      study of an urban EMS system and an urban ED. We studied 141 consecutive patients
      (47 children and 94 adults, matched by date of presentation) in cardiopulmonary
      arrest who were transported to the pediatric and adult EDs by ALS-trained
      prehospital providers (paramedics) between January 1992 and July 1995. We
      reviewed ambulance trip reports and ED records to determine when and which
      interventions were performed in the prehospital setting. Significance of
      differences between the groups was determined with Fisher's exact test and
      Student's t test. RESULTS: In 47 children (median age, 1 year; range, 2 days to
      15 years) and 94 adults (median age, 67 years; range, 16 to 95 years),
      pulselessness was documented at the time of the initial response of the ALS
      provider. Basic life support was performed in all patients. Among the 21 children
      and 7 adults who were not intubated, intubation was attempted in 13 children
      (62%) and in 6 adults (86%) (P = .26). Among the 29 children and 16 adults in
      whom intravascular access was not established, unsuccessful attempts to establish
      access were made in 1 child (3%) and in 15 adults (94%) (P = .0001). Among the 30
      children and 91 adults who were intubated, in whom intravascular access was
      established, or both, epinephrine was not administered to 12 children (40%) and 6
      adults (7%) (P < .0001). CONCLUSION: In our study population endotracheal
      intubation, intravascular access, and administration of epinephrine were
      attempted and performed significantly less frequently in children than in adults.
      Given the relative infrequency with which ALS providers encounter children in
      cardiopulmonary arrest, they need additional training to maintain their skills.

PMID- 9174520
TI  - Insulin improves survival in a canine model of acute beta-blocker toxicity.
AB  - STUDY OBJECTIVE: To compare the efficacy of a novel antidote, insulin, with
      standard treatments, glucagon and epinephrine, in a canine model of acute beta
      blocker toxicity. METHODS: Anesthetized dogs were fitted with instruments by
      means of thoracotomy and vascular cutdown for multiple cardiodynamic,
      hemodynamic, metabolic, and electrical measures. After basal measurements were
      taken, animals received intravenous propranolol (.25 mg/kg/minute) continuously
      for the remainder of the experiment. Toxicity was defined as a 25% decrease in
      the product of heart rate times mean blood pressure. Thirty minutes after the
      development of toxicity, toxic measures were taken (treatment 0 minutes), and
      then the animals (n = 6 each group) received either sham (saline solution),
      insulin (4 IU/minute with glucose clamped), glucagon (50 micrograms/kg bolus,
      then 150 micrograms/kg/hour infusion), or epinephrine (1 microgram/kg/minute).
      Animals were monitored until death or for 240 minutes. RESULTS: Propranolol
      decreased contractility, left ventricular pressure, and systemic blood pressure,
      and resulted in death of all sham-treated animals by 150 minutes. Six of six
      insulin-treated, four of six glucagon-treated, and one of six epinephrine-treated
      animals survived. Survival was greater for insulin-treated animals, compared with
      either glucagon-treated (P < .05) or epinephrine-treated animals (P < .02) by the
      log-rank test. Insulin-treated animals were characterized by improved
      cardiodynamics and hemodynamics, increased myocardial glucose uptake, and
      decreased serum potassium. CONCLUSION: Insulin is a superior antidote compared
      with glucagon or epinephrine in an anesthetized canine model of acute beta
      blocker toxicity.

PMID- 9174521
TI  - Neuroprotective effects of acetyl-L-carnitine after stroke in rats.
AB  - STUDY OBJECTIVE: To test the hypothesis that acetyl-L-carnitine (ALCAR) promotes
      neurologic recovery from experimental focal cerebral ischemia (stroke) in rats.
      METHODS: We conducted a prospective, randomized, blinded study in which adult
      male Sprague-Dawley rats were subjected to coagulative occlusion of the distal
      right middle cerebral artery (MCA) and temporary occlusion of both common carotid
      arteries (CCAs) for 60 minutes. After the onset of ischemia each rat was given
      ALCAR (200 mg/kg) or a similar volume of drug vehicle. Neurologic evaluation was
      performed on postoperative days 1, 2, 3, and 7. Postoperative weight loss was
      measured at day 7. Infarct volume was measured in separate groups of rats at 24
      hours. RESULTS: Neurologic outcomes, as assessed with an 11-point neurologic
      deficit scoring system, were significantly improved in ALCAR-treated rats on days
      1, 2, and 3 (P < .05). Improvement approached significance on day 7. Rats treated
      with ALCAR also demonstrated significantly less weight loss on day 7 compared
      with the vehicle-treated controls. We detected no differences, however, in
      infarct volumes measured between treatment groups. CONCLUSION: Although we noted
      no differences in infarct volume, postischemic treatment with ALCAR did improve
      early clinical recovery and prevented significant weight loss in this rat model
      of focal cerebral ischemia.

PMID- 9174522
TI  - Do wrist guards protect against fractures?
AB  - STUDY OBJECTIVE: To determine whether wrist guards increase the fracture
      threshold for wrist and forearm fractures. METHODS: We conducted a controlled,
      blinded experimental study using matched cadaveric arms-one fitted with a wrist
      guard-dropped with the use of a device designed to simulate a fall. We measured
      the mean number of drops before the occurrence of fracture, mean height and
      velocity change to fracture, mean kinetic energy, mean peak acceleration (in Gs),
      and summed impulse [weight (kilograms) x delta velocity (meters/second)] to
      fracture with and without wrist guards. Fracture severity was compared with the
      use of an ordinal ranking system and analyzed with the Mann-Whitney rank-sum
      test. RESULTS: Wrist guards were associated with a statistically significant
      increase in the number of drops, mean drop height, mean kinetic energy, and
      summed impulse required to cause a fracture. Fractures also tended to be less
      severe when wrist guards were used. CONCLUSION: The biomechanical evidence of a
      protective effect of wrist guards against wrist fractures seen in this study,
      coupled with previous epidemiologic evidence, is strong enough to warrant
      pediatricians, family practitioners, and emergency physicians to counsel skaters
      to use these devices when using roller skates, skateboards, or in-line skates.

PMID- 9174523
TI  - Emergency department patients with assault injuries: previous injury and assault
      convictions.
AB  - STUDY OBJECTIVE: To compare the incidence of previous assault injury and assault
      conviction of patients presenting to the ED with assault injuries and the
      incidence of assault injury and conviction in nonassaulted control patients.
      METHODS: We conducted a retrospective, medical record-based case-control study of
      ED patients with assault injuries and matched controls presenting with medical
      and surgical problems unrelated to assault. The setting was the ED of a 900-bed
      teaching hospital and Level I trauma center in an urban area. Our subjects were
      50 patients who presented as victims of blunt trauma, 50 patients who presented
      with penetrating trauma, and 100 control subjects matched by age, sex, and ZIP
      code who presented concurrently with nonassault complaints. RESULTS: The overall
      rate of previous assault injury was 35% and did not differ between cases and
      controls. Fifty-three patients had a history of criminal conviction, and 23 had a
      history of conviction for assault. Fewer patients presenting with assault
      injuries than controls had a history of conviction for assault (odds ratio [OR],
      .3; P < .02). Patients with penetrating injuries had the lowest incidence of
      assault conviction (OR, .13; P < .02). The subgroup of case subjects with
      criminal records had a higher rate of previous injury than those without records
      (P < .003). CONCLUSION: ED patients with assault injuries did not have a history
      of assault injuries exceeding that of controls and were less likely to have been
      convicted of assault. Violence-prevention programs should be directed toward a
      broader population of ED patients instead of narrowly focusing on victims of
      assault.

PMID- 9174524
TI  - Differences in the out-of-hospital care of children and adults: more questions
      than answers.

PMID- 9174525
TI  - Ultrasound retrieval of foreign bodies.

PMID- 9174526
TI  - Injuries and illnesses of domestic violence.
AB  - Domestic violence (DV) is a common cofactor or cause of illness and injury in the
      emergency department. Research is hampered by varied definitions of DV and lack
      of epidemiologically sound surveys. Injuries related to DV are those common in
      assaultive injury. Trauma reported to have occurred in falls and accidents may
      actually be the result of DV. Medical complaints and psychiatric problems may
      also result from or be associated with DV. The record of DV detection in the ED
      remains poor.

PMID- 9174527
TI  - Hate crime violence and its emergency department management.
AB  - As the 21st century approaches, the United States is moving, toward a more
      pluralistic society with regard to race, ethnicity, and national origin. With
      this increase in diversity has come a resurgence of hate crime violence. Scant
      information is available in the medical literature about hate crime violence,
      hate groups, hate crime violence legislation, or the physical and psychologic
      sequelae of hate crime violence on the individual and its effects on the
      community. Guidelines for the treatment of victims of hate crime violence in the
      prehospital care setting, ED, and inpatient setting are proposed.

PMID- 9174528
TI  - Core content for emergency medicine. Task Force on the Core Content for Emergency
      Medicine Revision.

PMID- 9174529
TI  - National Highway Traffic Safety Administration (NHTSA) notes. New Technologies
      from NHTSA.

PMID- 9174530
TI  - Building a smarter car: visions of the future at NHTSA.

PMID- 9174531
TI  - Paradoxical vocal cord motion presenting as acute stridor.
AB  - We report the cases of two patients who presented with acute-onset stridor that
      did not respond to standard medical therapy. Both were eventually found to have
      paradoxical vocal cord motion (PVCM). The ED management of these patients is
      reviewed.

PMID- 9174532
TI  - Suicide with an air rifle.
AB  - We report the case of a 14-year-old boy who committed suicide with the use of an
      air rifle. We include a brief description of his clinical presentation and
      course, as well as radiography and autopsy findings. This case represents an
      uncommon mechanism of suicide with an instrument commonly possessed by
      adolescents and demonstrates the potential lethality of air rifles. Today's air
      rifles employ one of three gas-compression systems: pneumatic, spring-air or gas
      compression. They are capable of generating velocities between 200 and 770
      feet/second, enabling pellets or BBs to penetrate skin, soft tissue, and bone.
      This case also highlights the need for preventive measures, including public
      education and legislation.

PMID- 9174533
TI  - Fosphenytoin: worth the cost?

PMID- 9174534
TI  - Nitroglycerin and renal colic.

PMID- 9174535
TI  - Lethal defibrillator mishap.

PMID- 9174536
TI  - Migraine classification and pathophysiology.

PMID- 9174537
TI  - Use of pediatric sedation and analgesia. American College of Emergency
      Physicians.

PMID- 9174538
TI  - Blood alcohol concentration and driving. American College of Emergency
      Physicians.

PMID- 9174539
TI  - Patient records in the emergency department. American College of Emergency
      Physicians.

PMID- 9174540
TI  - Guidelines for undergraduate education in emergency medicine. American College of
      Emergency Physicians.

PMID- 9174541
TI  - Telephone orders in the ED. American College of Emergency Physicians. Emergency
      Medicine Practice Committee.

PMID- 9174542
TI  - Fatal pulmonary hemorrhage in patients with acute leukemia and fulminant
      pneumonia caused by Stenotrophomonas maltophilia.
AB  - Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia.
      Within a 3-month period we observed three such cases, all of which were
      associated with the gram-negative opportunistic pathogen Stenotrophomonas
      maltophilia. Since fatal lung bleeding had previously not been observed in
      conjunction with this organism, we collected the data from all patients with
      documented S. maltophilia infections or colonizations of the past year and
      analyzed the risk factors for a lethal outcome. A total of eight patients were
      identified. In the three patients with fatal hemorrhage, the interval between
      first complaints (chest pain, cough, fever) and death from lung bleeding was 36
      72 h. A fourth patient with acute leukemia died of nonhemorrhagic respiratory
      failure 9 days after developing S. maltophilia-associated pneumonia. All four
      patients had received intensive chemotherapy and were severely neutropenic and
      thrombocytopenic. Such a combination of predisposing factors was not observed in
      the four patients with nonfatal infections or colonizations. Pulsed-field gel
      electrophoresis demonstrated that the infections were unrelated. S. maltophilia
      was also isolated from a faucet in a patient's room, but the strain isolated was
      genetically different from the strain causing the patient's pneumonia. Our data
      suggest that severe bone marrow aplasia and a recent history of intensive
      chemotherapy are predisposing factors for the development of fulminant
      hemorrhagic S. maltophilia pneumonia. Since some of the infections and
      colonizations developed despite prophylactic administration of antibacterial
      agents with documented in vitro activity against the pathogen and none was
      controlled by such agents, it is clear an efficient treatment strategy needs to
      be developed.

PMID- 9174543
TI  - Ocular manifestations in adult T-cell leukemia/lymphoma.
AB  - Ocular manifestations of adult T-cell leukemia/lymphoma (ATL) are rare events.
      However, several ocular lesions which resulted from human T-cell leukemia virus
      type I (HTLV-I) infection have been reported, including direct infiltration of
      ATL cells, cytomegalovirus retinitis, and HTLV-I-associated uveitis (HAU). The
      aim of this study was to characterize ocular involvement in ATL and to correlate
      these lesions with HTLV-I proviral DNA integration. Three patients with acute
      type ATL and ocular lesions were evaluated hematologically and
      ophthalmologically. Analysis of HTLV-I proviral DNA was carried out with a
      standard Southern blot technique using DNA from abnormal lymphocytes in
      peripheral blood. Two patients developed intraocular lesions located within
      intermediate and/or posterior segments which were caused by infiltration of ATL
      cells. Ocular lesions in one patient, which were localized to the anterior
      intermediate segment, closely resembled those of HAU. Analysis of HTLV-I proviral
      DNA revealed multiple integrations in all three patients. The present study
      indicated heterogeneity in ocular manifestations of ATL. Multiple HTLV-I proviral
      DNA integrations may be associated with intraocular involvement in this disease.

PMID- 9174544
TI  - Blood concentrations of G-CSF and myelopoiesis in patients undergoing
      aortocoronary bypass surgery.
AB  - The pattern of changes in leukocyte counts and the blood concentration of G-CSF
      were observed in 15 patients undergoing aortocoronary bypass surgery.
      Myelopoietic function was assessed by examining the myelogram and performing flow
      cytometry to identify human leukocyte differentiation antigens on bone marrow
      aspirates obtained from the sternum when opening and closing the sternotomy. The
      blood concentration of G-CSF increased gradually after removal of the aortic
      cross clamp and peaked on the first postoperative day (232 +/- 98 ngml). The
      white blood cell count also increased during the operation and peaked on the
      second postoperative day, demonstrating a threefold increase (15,800 +/- 2700).
      Granulocytes represented most of the increase, while lymphocytes and monocytes
      showed no significant changes. The myelogram showed that the percentages of
      myeloblasts, promyelocytes, and metamyelocytes did not change; however, the
      percentage of myelocytes increased significantly during surgery (14.0 +/- 2.5%
      vs. 17.3 +/- 3.5%, p < 0.05). The number of mature myelocytes (LFA-1 beta and Leu
      15 positive) decreased significantly (p < 0.01 and p < 0.05) during surgery. With
      the two-color method, the ratio of immature myelocytes (MCS-2 negative and Leu-15
      negative) increased significantly (p < 0.01). The ratio of myeloblasts (Leu-11
      and HLA-DR positive) and the ratio of stem cells (CD 34 and MY-9 positive) did
      not increase significantly during the operation. G-CSF concentrations increase
      substantially during aortocoronary bypass surgery and may be responsible for the
      rise in granulocyte and total leukocyte counts, as well as for the increase in
      immature myelocytes seen on bone marrow examination.

PMID- 9174545
TI  - The abundant presence of Soderstrom bodies in cytology smears of fine-needle
      aspirates contributes to distinguishing high-grade non-Hodgkin's lymphoma from
      carcinoma and sarcoma.
AB  - Soderstrom bodies, also termed lymphoglandular bodies (LGB) and detectable in
      fine-needle aspiration cytology smears, have long been accepted as indicative of
      lymphoid tissues. To investigate the validity of this association, we examined
      588 cytologic smears from high-grade non-Hodgkin's lymphoma (NHL), carcinoma, and
      sarcoma. Slides with lymphocytes in the vicinity of carcinoma and sarcoma cells
      had been excluded. Two independent observers scored smears to number, size,
      color, form, and smear background of the LGB. In 68 of 359 (19%) nonlymphoid
      malignancies rare (defined as < 1 LGB per high-power field) or occasional LGB
      (defined as 1-20 LGB per high-power field) were detectable. Half of these tumors
      consisted of melanomas, small cell lung carcinomas, and teratomas; the other half
      encompassed undifferentiated sarcomas. However, none of the smears obtained from
      carcinoma or sarcoma tissue had abundant LGB (defined as > 20 LGB per high-power
      field). When number of LGB was estimated to be abundant, the sensitivity for
      diagnosing a lymphoma was 54%; however, specificity was 100%. The difference in
      showing LGB between high-grade NHL and carcinoma/sarcoma was highly significant
      (p = 0.0001). The presence of abundant LGB in cytologic smears strongly suggests
      the diagnosis of lymphoma, while the absence of LGB nearly excludes this
      diagnosis. No trends were observed with the other criteria which were tested. LGB
      in aspiration cytology smears from malignant tumors thus represent a useful tool
      to distinguish high-grade NHL from carcinoma and sarcoma.

PMID- 9174547
TI  - Frequency and causes of refractoriness in multiply transfused patients.
AB  - The use of leukocyte-depleted blood components has become the standard therapy
      for multiply transfused patients during the past few years, as a measure to
      reduce the frequency of alloimmunization and refractoriness. We assessed
      frequency and causes of refractoriness, defined as a repeated 24-h post
      transfusion platelet count below 20,000/microliters, in 145 consecutive patients
      who received three or more single-donor platelet concentrates during a 1-year
      period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein
      specific ELISA were applied for the diagnosis of alloimmunization. Forty patients
      (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients
      (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were
      the cause. In 15 refractory patients alloantibodies were detected. In seven
      patients (17.5%), alloimmunization alone caused an inadequate transfusion
      response, while in eight refractory patients (20.0%) alloimmunization and fever
      or sepsis were present. HLA antibodies were detected in 17 patients (11.7%);
      three patients (2%) had platelet-specific antibodies in addition to HLA
      antibodies; in two patients panreactive platelet antibodies were detectable. All
      17 patients had a history of previous transfusions or pregnancy. We did not
      observe primary immunization in patients transfused exclusively with filtered
      (leukodepleted) blood products. Our data suggest that alloimmunization in
      patients with a negative risk history can be prevented by the exclusive use of
      leukodepleted blood components.

PMID- 9174546
TI  - Thrombocytopenia and complement activation under recombinant TNF alpha/IFN gamma
      therapy in man.
AB  - Infusions of recombinant human tumor necrosis-alpha plus recombinant human
      interferon-gamma (rhTNF alpha/rhIFN gamma) were assessed in two patients with
      Ewing's sarcoma. We analyzed platelet count, coagulation and the terminal
      complement complex (TCC). During cycles with continuous rhTNF alpha-infusions we
      found a rapid, marked decrease of platelet count (minus 90% of initial values)
      and a simultaneous increase of TCC (plus 84% of initial values) at day 4. At days
      5-7 a spontaneous increase of platelet count and decrease of TCC were visible.
      Short-term infusion led to a milder, continuous decrease of platelet counts and
      to a moderate, progressive increase of TCC at days 5-7. Bleeding occurred only as
      petechia and mild hemoglobinuria. There was no effect related to the dosage of
      rhTNF alpha or rhIFN gamma. Relevant differences were seen only in the variable
      time courses of rhTNF alpha application. Ex vivo analysis of one patient's
      platelets showed no cytokine-related effect on induced aggregation according to
      Born. Additionally, we analyzed in vitro effects of the cytokines on platelet
      count, platelet aggregation, and the assembly of TCC in platelet membranes. No
      effects were found after incubation of platelet-rich plasma (PRP) with 1000 pg/ml
      rhTNF alpha and/or 50 pg/ml rhIFN gamma. Fluid-phase and membrane-bound TCC did
      not change after incubation of PRP with cytokines. A slightly time-dependent
      increase of TCC without alteration of platelet count and platelet function did
      not agree with the assumption of a direct injury to platelets. We assume a
      cytokine-mediated role of the endothelium in platelet loss.

PMID- 9174548
TI  - Primary transplantation of allogeneic peripheral blood stem cell for severe
      aplastic anemia.
AB  - Primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has
      not been previously described in the treatment of severe aplastic anemia (SAA).
      We report a patient with SAA who underwent primary allo-PBSCT with cells from her
      HLA-identical sibling and achieved rapid bone marrow reconstitution. The patient
      has been in complete remission with normal blood counts for 9 months following
      allo-PBSCT. This suggests that primary allo-PBSCT is a safe and effective
      alternative in the treatment of SAA.

PMID- 9174549
TI  - Myelodysplastic syndrome/acute myeloid leukemia supervening previously untreated
      chronic B-lymphocytic leukemia: demonstration of the concomitant presence of two
      different malignant clones by immunologic and molecular analysis.
AB  - The development of myelodysplastic syndrome (MDS) and/or acute myeloid leukemia
      (AML) has rarely been observed in patients with chronic B-lymphocytic leukemia (B
      CLL). So far, the discussion concerning the pathogenesis of the simultaneous
      occurrence of these two malignancies has been speculative, opposing the theory of
      two separate malignant clones to the theory of a common stem cell malignancy. We
      describe the case of a 77-year-old woman who developed MDS after 8 years of an
      indolent course of B-CLL. The diagnosis of MDS was based on bone marrow (BM)
      morphology, showing the typical picture of a refractory anemia with excess of
      blasts (RAEB). The clinical course of MDS was aggressive, terminating in AML
      within only 6 months. Immunophenotyping of BM and peripheral blood (PB) cells
      revealed a CD34+/ CD13+/CD33-/CD19-blast cell population and a CD19+/CD5+ B-cell
      population with kappa light chain restriction. Molecular analysis of PB and BM
      demonstrated the presence of an immunoglobulin heavy chain (IgH) gene
      rearrangement by polymerase chain reaction (PCR) amplification of genomic DNA
      with three different pairs of consensus primers. Cell-sorting experiments showed
      that the IgH gene rearrangement was present only in the CD19+/CD34- B-cell
      population, but not in the CD34+/CD19- blast cells. Furthermore, X-chromosome
      inactivation pattern analysis revealed two differently methylated cell
      populations. These experiments demonstrate the concomitant existence of two
      different clones in a patient with CLL-MDS/AML.

PMID- 9174550
TI  - Primary acquired sideroblastic anemia, thrombocytosis, and trisomy 8.
AB  - Myelodysplastic syndromes are usually associated with pancytopenia. Disorders
      involving deletion of the long arm of chromosome 5 (5q-syndrome) and, rarely,
      patients with karyotypic abnormalities involving chromosome 3 associated with
      abnormal thrombopoiesis may have a normal or even raised platelet count. Other
      cytogenetic abnormalities in myelodysplasia are invariably associated with
      cytopenia in one or all cell lineages. We report a patient who initially
      presented with slight anemia and a raised platelet count. Further investigations
      suggested a diagnosis of primary acquired sideroblastic anemia. Cytogenetic
      examination revealed a clone with trisomy 8. We believe this is the first
      reported case of trisomy 8 with trilineage myelodysplasia and thrombocytosis with
      primary acquired sideroblastic anemia.

PMID- 9174551
TI  - The occurrence of T-cell malignancies in patients treated by chemotherapy for
      acute myeloid leukemia.

PMID- 9174552
TI  - A better future in stroke?

PMID- 9174553
TI  - Aspirin or heparin immediately after a stroke?

PMID- 9174554
TI  - Does paroxysmal atrial fibrillation confer a paroxysmal thromboembolic risk?

PMID- 9174555
TI  - Epiluminescence microscopy in clinical diagnosis of pigmented skin lesions?

PMID- 9174556
TI  - Postural drainage techniques and gastro-oesophageal reflux in cystic fibrosis.

PMID- 9174557
TI  - Legacy of war: beyond "trauma" to the social fabric.

PMID- 9174558
TI  - The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous
      heparin, both, or neither among 19435 patients with acute ischaemic stroke.
      International Stroke Trial Collaborative Group.
AB  - BACKGROUND: Only a few small trials have compared antithrombotic therapy
      (antiplatelet or anticoagulant agents) versus control in acute ischaemic stroke,
      and none has been large enough to provide reliable evidence on safety or
      efficacy. METHODS: The International Stroke Trial (IST) was a large, randomised,
      open trial of up to 14 days of antithrombotic therapy started as soon as possible
      after stroke onset. The aim was to provide reliable evidence on the safety and
      efficacy of aspirin and of subcutaneous heparin. Half the patients were allocated
      unfractionated heparin (5000 or 12,500 IU bd [twice daily]), and half were
      allocated "avoid heparin"; and, in a factorial design, half were allocated
      aspirin 300 mg daily and half "avoid aspirin". The primary outcomes were death
      within 14 days and death or dependency at 6 months. 19,435 patients with
      suspected acute ischaemic stroke entering 467 hospitals in 36 countries were
      randomised within 48 hours of symptom onset. RESULTS: Among heparin-allocated
      patients, there were non-significantly fewer deaths within 14 days (876 [9.0%]
      heparin vs 905 [9.3%] no heparin), corresponding to 3 (SD 4) fewer deaths per
      1000 patients. At 6 months the percentage dead or dependent was identical in both
      groups (62.9%). Patients allocated to heparin had significantly fewer recurrent
      ischaemic strokes within 14 days (2.9% vs 3.8%) but this was offset by a similar
      sized increase in haemorrhagic strokes (1.2% vs 0.4%), so the difference in death
      or non-fatal recurrent stroke (11.7% vs 12.0%) was not significant. Heparin was
      associated with a significant excess of 9 (SD 1) transfused or fatal extracranial
      bleeds per 1000. Compared with 5000 IU bd heparin, 12,500 IU bd heparin was
      associated with significantly more transfused or fatal extracranial bleeds, more
      haemorrhagic strokes, and more deaths or non-fatal strokes within 14 days (12.6%
      vs 10.8%). Among aspirin-allocated patients there were non-significantly fewer
      deaths within 14 days (872 [9.0%] vs 909 [9.4%]), corresponding to 4 (SD 4) fewer
      deaths per 1000 patients. At 6 months there was a non-significant trend towards a
      smaller percentage of the aspirin group being dead or dependent (62.2% vs 63.5%,
      2p = 0.07), a difference of 13 (SD 7) per 1000; after adjustment for baseline
      prognosis the benefit from aspirin was significant (14 [SD 6] per 1000, 2p =
      0.03). Aspirin-allocated patients had significantly fewer recurrent ischaemic
      strokes within 14 days (2.8% vs 3.9%) with no significant excess of haemorrhagic
      strokes (0.9% vs 0.8%), so the reduction in death or non-fatal recurrent stroke
      with aspirin (11.3% vs 12.4%) was significant. Aspirin was associated with a
      significant excess of 5 (SD 1) transfused or fatal extracranial bleeds per 1000;
      in the absence of heparin the excess was 2 (SD 1) and was not significant. There
      was no interaction between aspirin and heparin in the main outcomes.
      INTERPRETATION: Neither heparin regimen offered any clinical advantage at 6
      months. The results suggest that if heparin is given in routine clinical
      practice, the dose should not exceed 5000 IU subcutaneously twice daily. For
      aspirin, the IST suggests a small but worthwhile improvement at 6 months. Taking
      the IST together with the comparably large Chinese Acute Stroke Trial, aspirin
      produces a small but real reduction of about 10 deaths or recurrent strokes per
      1000 during the first few weeks. Both trials suggest that aspirin should be
      started as soon as possible after the onset of ischaemic stroke; previous trials
      have already shown that continuation of low-dose aspirin gives protection in the
      longer term.

PMID- 9174559
TI  - Increased plasma viscosity during an air pollution episode: a link to mortality?
AB  - BACKGROUND: Air pollution episodes have been consistently associated with
      increased mortality, and most strikingly with mortality due to cardiovascular
      disease. One hypothesis to explain this association is that inflammation of the
      peripheral airways caused by pollution might increase blood coagulability. We
      have tested this hypothesis in a cross-sectional study by comparing measurements
      of plasma viscosity during a severe episode of air pollution during 1985 with
      those made on less polluted days. METHODS: Plasma viscosity was measured as part
      of the MONICA Augsburg survey during the winter of 1984-85 in 3256 randomly
      selected men and women aged 25-64 years. Daily mean concentrations of air
      pollutants and meteorological variables were measured in Augsburg as part of the
      automated Bavarian air-quality network. We compared measurements of plasma
      viscosity made in 324 people who attended for screening during the pollution
      episode and in 2932 people screened during the remainder of the survey period.
      FINDINGS: In January, 1985, high concentrations of sulphur dioxide (mean 200
      micrograms/m3) and total suspended particles (mean 98 micrograms/m3) were
      recorded during a 13-day period in Augsburg. In men, the odds ratio for plasma
      viscosity above the 95th percentile of the distribution (1.38 mPa s) was 3.6 (95%
      CI 1.6-8.1) comparing measurements during the air pollution episode with non
      episode measurements after adjustment for cardiovascular risk factors and
      meteorological variables. The corresponding odds ratio for women (95th percentile
      of plasma viscosity 1.37 mPa s) was 2.3 (1.0-5.3). High concentrations of carbon
      monoxide were also associated with increased plasma viscosity in women.
      INTERPRETATION: During the 1985 air pollution episode, an increased risk of
      extreme values of plasma viscosity was observed in both men and women. Altered
      blood rheology due to inflammatory processes in the lung that induce an acute
      phase reaction might therefore be part of the pathological mechanisms linking air
      pollution to mortality.

PMID- 9174560
TI  - Offspring recurrence rates and clinical characteristics of conjugal multiple
      sclerosis.
AB  - BACKGROUND: There has been no previous systematic study of conjugal multiple
      sclerosis. This study of conjugal pairs with complex traits investigated disease
      transmissibility and the genetic contribution to frequency and clinical course.
      METHODS: We studied 45 conjugal pairs concordant for multiple sclerosis from 58
      pairs recorded in a national register of familial disease, 86 offspring of the 45
      pairs were individually assessed for clinical evidence of neurological disease;
      those over age 16 underwent cranial magnetic resonance imaging. Clinical features
      were compared in 33 pairs in whom neither member had symptoms before they met.
      FINDINGS: Of the 86 offspring, five (6%) had clinically definite multiple
      sclerosis. A further five children had either characteristic imaging
      abnormalities or clinical symptoms consistent with demyelination, but did not
      meet the criteria for clinically definite disease. There was no evidence of
      clinical concordance, clustering at year of onset, or distortion of the expected
      pattern of age of onset in the second affected spouse from 33 pairs. The crude
      recurrence in children of conjugal pairs (1 in 17) is significantly higher than
      previously reported population-based risk for offspring of single affected
      parents (1 in 200). INTERPRETATION: Taken with the low prevalence of multiple
      sclerosis in the spouses of affected individuals, and the lack of concordance for
      age at onset in these families, the disparity in crude recurrence between
      children of conjugal pairs and those of single affected parents shows that the
      recurrence risk in children is determined by genetic factors inherited from both
      parents.

PMID- 9174561
TI  - Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with
      low red-cell folates: implications for folate intake recommendations.
AB  - BACKGROUND: The dietary reference values for folate, as for other nutrients, are
      targeted to the general and supposedly normal population, not people with special
      needs, such as those with genetic or metabolic abnormalities or diseases.
      However, 5-15% of general populations are homozygous for a thermolabile variant
      of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild
      hyperhomocysteinaemia and is positively associated with the development of
      vascular disease and the risk of neural-tube defects. If tissue-folate status is
      compromised in large sectors of the population by this or other genetic variants,
      the present dietary reference values may need to be changed. METHODS: We
      identified the C677T genotype and measured red-cell folate concentrations in two
      groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the
      effect of genotype on red-cell folates, which are a reliable marker for tissue
      folate stores. FINDINGS: In the pregnant group there were 20 TT homozygotes, 114
      wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group,
      the numbers were 41, 148, and 129. In both pregnant and non-pregnant groups, red
      cell folate was significantly lower among TT homozygous than CC homozygous women
      (mean 252 [95% CI 202-317] vs 347 [321-372] micrograms/L, p = 0.002 for pregnant
      women; 284 [250-327] vs 347 [342-372] micrograms/L, p = 0.01 for non-pregnant
      women). Plasma folate was also significantly lower in TT homozygous than in CC
      homozygous women in the pregnant group (p = 0.009) but not in the non-pregnant
      group. INTERPRETATION: These results suggest that a substantial minority of
      people in general populations may have increased folate needs. Future studies may
      show the presence of other common genetic variants that interact with particular
      nutrients and place doubts on the validity of assuming "normality" for nutrient
      requirements in any general population.

PMID- 9174562
TI  - Randomised, double-blind, placebo-controlled trial of pindolol in combination
      with fluoxetine antidepressant treatment.
AB  - BACKGROUND: Major depression affects more than 5% of the population and is a
      serious health and economic problem. Antidepressants have a slow onset of action
      and are effective in less than two-thirds of patients. The biochemical effects of
      selective serotonin reuptake inhibitors may be limited by the negative feedback
      from serotonin autoreceptors. Pindolol is an antagonist of both serotonin
      autoreceptors and beta-adrenoceptors. We studied the effect of the addition of
      pindolol to fluoxetine antidepressant treatment. METHODS: Of 132 eligible
      patients with major depression, 111 were randomly assigned to treatment with
      fluoxetine (20 mg daily) and either placebo or pindolol (7.5 mg daily). Patients
      were assessed twice a week for the first 3 weeks of active treatment and then
      once a week until the end of the study (42 days). Hamilton and Montgomery-Asberg
      depression-rating scales were used to assess depression severity. FINDINGS: The
      proportion of patients who responded to treatment with fluoxetine and pindolol
      was greater than that with fluoxetine and placebo (41/55 [75%] vs 33/56 [59%],
      [90% CI 1.1-30.1], p = 0.04). The proportion of patients who achieved a sustained
      response was also greater in the fluoxetine and pindolol group than in the
      fluoxetine and placebo group (38/55 [69%] vs 27/56 [48%] [5.9-35.9], p = 0.03).
      The number of days to reach a sustained response was lower in the fluoxetine and
      pindolol group than in the fluoxetine and placebo group (median 19 vs 29 days, p
      = 0.01), however, there was no difference in the time-to-onset of clinical
      improvement when stringent conditions were used (15 vs 18 days, p = 0.20).
      INTERPRETATION: The addition of pindolol to fluoxetine antidepressant treatment
      increases the effectiveness of fluoxetine therapy. Further work is needed to
      resolve whether the time to clinical improvement benefits from this combination
      and whether the increase in efficacy occurs with other antidepressants.

PMID- 9174563
TI  - A malicious mould.

PMID- 9174564
TI  - Ischaemic brain tissue salvaged from infarction with alteplase.

PMID- 9174565
TI  - Polymyositis associated with simvastatin.

PMID- 9174566
TI  - Prostate-specific membrane antigen in breast carcinoma.

PMID- 9174567
TI  - Symptoms and signs of severe citalopram overdose.

PMID- 9174568
TI  - Clinical value of ACE genotyping in diagnosis of sarcoidosis.

PMID- 9174569
TI  - Is codon 129 of prion protein polymorphic in human beings but not in animals?

PMID- 9174570
TI  - Sleep apnoea as a cause of daytime and nocturnal enuresis.

PMID- 9174571
TI  - The acute porphyrias.

PMID- 9174572
TI  - Literature and medicine: narratives of physical illness.

PMID- 9174573
TI  - Oral contraceptives and venous thromboembolism.

PMID- 9174574
TI  - Oral contraceptives and venous thromboembolism.

PMID- 9174575
TI  - Oral contraceptives and venous thromboembolism.

PMID- 9174576
TI  - Oral contraceptives and venous thromboembolism.

PMID- 9174577
TI  - Musculoskeletal side-effects of varicella.

PMID- 9174578
TI  - Effect of hormone replacement therapy on cancer detection by mammography.

PMID- 9174579
TI  - Effect of hormone replacement therapy on cancer detection by mammography.

PMID- 9174580
TI  - Measles vaccine and neurological events.

PMID- 9174581
TI  - Genetic versus environmental factors in insulin-dependent diabetes mellitus.

PMID- 9174582
TI  - Is vaccination of donor adequate for clearance of hepatitis B virus after bone
      marrow transplantation?

PMID- 9174584
TI  - Diagnosis of intracranial injury.

PMID- 9174583
TI  - Diagnosis of intracranial injury.

PMID- 9174585
TI  - Wheat and chaff in alternative medicine.

PMID- 9174586
TI  - Wheat and chaff in alternative medicine.

PMID- 9174587
TI  - Elderly pilots.

PMID- 9174589
TI  - The when and how of advocacy.

PMID- 9174588
TI  - Conquering poliomyelitis in India.

PMID- 9174590
TI  - Do not go flying in short sleeves.

PMID- 9174591
TI  - Expression of two interleukin-15 mRNA isoforms in human tumors does not correlate
      with secretion: role of different signal peptides.
AB  - Interleukin (IL)-15 is a four-helix bundle cytokine sharing several biological
      properties with IL-2. By reverse transcriptase-polymerase chain reaction
      analysis, human cancer cell lines of different histotypes are shown to express
      two IL-15 amplification products: a 524-bp band corresponding to the IL-15 mRNA
      found in macrophages, and another of 643 bp corresponding to an alternatively
      spliced mRNA including a 119-bp alternative exon. IL-15 was undetectable in the
      supernatant of tumor cell lines expressing either one or both of the mRNA
      isoforms as evaluated by a bioassay or by ELISA, indicating that IL-15 is not
      secreted. However, IL-15 could be detected intracellularly in some tumor cells by
      confocal microscopy analysis. Since the pre-proteins encoded by the two mRNA
      isoforms differ in the signal peptide sequence, we have analyzed the
      characteristics of these signal peptides and their possible role in controlling
      secretion. The two IL-15 cDNA isoforms, expressed in COS-7 cells, induced very
      low levels of IL-15 secretion. However, substitution of the sequence encoding
      natural signal peptide(s) with the one from IgV kappa chain in the IL-15 cDNA
      results in a significantly higher secretion of biologically active IL-15 (15-30
      fold) upon cDNA transfection. A poor efficiency of natural signal peptides may
      represent one of the mechanisms involved in the control of IL-15 secretion.

PMID- 9174592
TI  - A complementarity-determining region peptide of an anti-desmosome autoantibody
      may interact with the desmosomal plaque through molecular mimicry with a
      cytoplasmic desmoglein 1 sequence.
AB  - The sera of patients with pemphigus, a group of autoimmune blistering skin
      diseases, contain autoantibodies directed against components of adhering
      junctions termed desmosomes. F12, a human monoclonal antibody derived from a
      pemphigus patient, recognizes an unknown polypeptide of the desmosomal and
      hemidesmosomal plaques. The third complementarity-determining region of the F12
      heavy chain (VH-CDR3) was shown to share a four-amino-acid sequence (GSSG) with
      the intracellular domains of desmoglein 1 and bullous pemphigoid antigen 2 which
      interact with components of, respectively, the desmosomal and hemidesmosomal
      plaques. Computer modeling of F12 showed that the GSSG sequence protudes inside
      the antigen-combining site and thus might be involved in antigen interactions.
      The GSSG sequence is essential to F12 function, since a peptide containing the VH
      CDR3 inhibited its binding to target antigens while VH-CDR3 peptides with
      specific modifications of the GSSG sequence did not. These data allow us to
      hypothesize that certain autoantibodies produced during the course of an
      autoimmune disease can behave as adhesion molecules, through the molecular
      mimicry of the motif involved in protein/protein adhesion, and to propose a new
      self-antigen binding mechanism for some autoantibodies.

PMID- 9174593
TI  - RANTES stimulation of T lymphocyte adhesion and activation: role for LFA-1 and
      ICAM-3.
AB  - The chemokine RANTES is a potent chemoattractant and activator of T lymphocytes.
      Mechanisms underlying the RANTES-induced activation of T lymphocytes leading to
      adhesion and migration have not been fully analyzed. We investigate here the
      function of RANTES in the regulation of T cell adhesion, specifically the
      induction of homotypic aggregation. RANTES induced the expression of many
      important cell surface adhesion and activation receptors in a normal human T cell
      clone and peripheral blood T lymphocytes, including members of the beta 1 and
      beta 2 integrin family, CD44, CD50, and CD28. Up-regulation of these markers
      correlated with RANTES-stimulated homotypic adhesion of T cells. This homotypic
      aggregation event was RANTES dose-dependent, prolonged, and pertussis toxin
      independent, but herbimycin A-sensitive, suggesting that it involves signaling
      through alternative (G alpha i protein-independent) pathways. Using specific
      monoclonal antibodies, the homotypic aggregation event was shown to be lymphocyte
      function-associated antigen-1 (LFA-1)-dependent, with no observable interaction
      through alpha 4 or beta 1 integrins. Intercellular adhesion molecule-3 (ICAM-3)
      and possibly ICAM-1 participate as LFA-1 ligands. Additionally, RANTES
      phosphorylated the beta chain of LFA-1 1-2 min following stimulation. These
      results imply a specific role for the chemokine RANTES in T cell activation and
      intercellular adhesion.

PMID- 9174594
TI  - Does positive selection determine the B cell repertoire?
AB  - To know whether each newly formed B cell has an equal chance of survival in the
      organism, we analyzed the composition of the B cell repertoire of extremely
      limited diversity by generating mu-transgenic kappa-knockout mice. Surprisingly,
      in both types of mice studied, the B cell repertoire is mainly composed of cells
      expressing the mu-transgene-encoded chain associated with only one out four
      available lambda types depending on the mu transgene. Moreover, B cell
      differentiation cultures in vitro show that newly formed B cells can express the
      various lambda types regardless of the presence or absence of the mu transgenes.
      These results show a drastic impact of the heavy chain on the lambda light chain
      repertoire expressed in the periphery. The overexpression of a unique heavy/light
      chain pairing therefore results from selective processes. The immature B cells
      may be positively selected to provide the immunocompetent B cells in the
      periphery.

PMID- 9174595
TI  - Post-translational up-regulation of the cell surface-associated alpha component
      of the human type I interferon receptor during differentiation of peripheral
      blood monocytes: role in the biological response to type I interferon.
AB  - Human peripheral blood monocytes cultured in vitro exhibit a greater sensitivity
      to the antiviral effect of type I interferon (IFN) compared to freshly isolated
      monocytes. We evaluated the effect of macrophage differentiation on the
      expression of type I IFN receptors (IFN-R). Binding studies with iodinated IFN
      alpha 2 and Scatchard plot analysis revealed that a single class of high-affinity
      receptors was present in freshly isolated monocytes. Monocyte differentiation to
      macrophages resulted in a three- to fourfold increase in the number of cell
      surface receptors with no change in their affinity. Polymerase chain reaction
      analysis of RNA revealed that comparable levels of mRNA for the IFN-R alpha
      (IFNAR1) and IFNAR2 components were expressed in freshly isolated monocytes and 7
      day cultured macrophages. Likewise, the levels of IFNAR1 protein remained
      constant over time in culture. Immunofluorescence studies revealed that IFNAR1
      was localized in intracellular compartments of freshly isolated monocytes,
      whereas it was predominantly detected on the cell surface in 7-day cultured
      macrophages. The increased expression of IFN-R on the plasma membrane of cultured
      macrophages may, at least in part, account for the increased antiviral effect of
      type I IFN in these cells. These modifications represent one of the events
      occurring during monocyte differentiation that may play a role in the regulation
      of macrophage functions.

PMID- 9174596
TI  - Co-stimulatory pathways controlling activation and peripheral tolerance of human
      CD4+CD28- T cells.
AB  - Co-stimulation mediated by the CD28 molecule is considered critical in the
      activation of CD4+ T cells. In patients with rheumatoid arthritis and
      infrequently in normal individuals, CD4+ T cells lacking CD28 expression are
      expanded and contain clonogenic populations. To analyze whether these cells are
      independent of co-stimulatory requirements or whether they use co-stimulatory
      signals distinct from the CD28 pathway, we have compared CD4+ CD28+ and CD4+ CD28
      T cell clones isolated from rheumatoid arthritis patients. Accessory cells
      supported the induction of CD25 expression as well as of proliferative responses
      after anti-CD3 cross-linking and prevented the induction of anergy in CD4+ CD28-
      T cell clones. In contrast to CD4+CD28+ T cells, the presence of accessory cells
      did not enhance the secretion of interleukin (IL)-2, interferon-gamma, or IL-4.
      The co-stimulatory signals did not involve CD28/CTLA-4-CD80/CD86 receptor-ligand
      interactions. The proliferative response of CD4+CD28- T cells could not be
      blocked by anti-CD2, anti-CD18, and anti-CD58 antibodies, suggesting that these
      receptor-ligand interactions cannot provide CD28- independent co-stimulation. Our
      data suggest that CD4+CD28- T cells require co-stimulatory signals for optimal
      induction of cell growth and CD25 expression as well as for the prevention of
      anergy. The co-stimulatory receptor-ligand interaction is independent of the CD28
      pathway and may be involved in the oligoclonal expansion of the CD4+ CD28- T cell
      subset in rheumatoid arthritis.

PMID- 9174597
TI  - Cytokine induction of monocyte chemoattractant protein-1 gene expression in human
      endothelial cells depends on the cooperative action of NF-kappa B and AP-1.
AB  - Chemokines are potent mediators of cell migration and activation and therefore
      play an essential role in early events of inflammation. In conjunction with cell
      adhesion molecules, chemokines help to localize cells to a specific site and
      enhance the inflammatory reaction at the site. Clinically, elevated levels of
      chemokines have been found in a variety of inflammatory diseases. The prototype C
      C chemokine is monocyte chemoattractant protein-1 (MCP-1) which is synthesized by
      variety of cell types including endothelial cells in response to a variety of
      stimuli. MCP-1 is a major chemoattractant for monocytes, T lymphocytes, and
      basophils. In the present study, we investigated the factors involved in cytokine
      induced MCP-1 gene expression in human endothelial cells. We present evidence
      that the nuclear factor (NF)-kappa B-like binding site and the AP-1 binding site
      located 90 and 68 base pairs upstream of the transcriptional start site,
      respectively, are required for maximal induction of the human MCP-1 promoter by
      interleukin-(IL)-1 beta. Site-directed mutagenesis or deletion of the NF-kappa B
      like site decreased the cytokine-induced activity of the promoter. Site-directed
      mutagenesis of the AP-1 binding site also decreased the cytokine-induced activity
      of the promoter. We show that the NF-kappa B-like site located at-90 in the MCP-1
      promoter binds to the p50/p65 heterodimer of the NF-kappa B/Rel family in IL-1
      beta-stimulated human endothelial cells. Overexpression of p65 results in the
      transactivation of the MCP-1 promoter as well. The data presented in this study
      suggest that cytokine-induced MCP-1 gene expression in human endothelial cells
      depends on the cooperative action of NF-kappa B and AP-1.

PMID- 9174599
TI  - Agonist antibody and Fas ligand mediate different sensitivity to death in the
      signaling pathways of Fas and cytoplasmic mutants.
AB  - We have produced three forms of human Fas: full-length Fas, Fas with a C-terminal
      deletion, and a chimera between extracellular Fas and the intracellular domain of
      the tumor necrosis factor receptor I p55 subunit. We transfected cell lines with
      these constructs to compare the relative capacity of antibody agonists and the
      physiological Fas ligand (FasL) to stimulate death. With two agonistic
      antibodies, the chimera is 100- to 1000-fold more sensitive to induction of death
      than the full-length Fas. The C-terminal deletion mutant also shows greatly
      enhanced death in comparison to the wild-type receptor. In contrast, when FasL is
      used to trigger the Fas pathway, wild-type Fas and the deletion mutant are
      similarly sensitive, whereas the chimera is 100-fold less susceptible to ligand
      mediated killing than Fas. This demonstrates that antibody agonists and natural
      ligand can stimulate different signaling pathways and emphasizes the limitations
      of defining physiologically important signaling pathways solely by antibody
      agonists.

PMID- 9174598
TI  - Constitutive and inducible protein/DNA interactions of the interferon-gamma
      promoter in vivo in [corrected] CD45RA and CD45R0 T helper subsets.
AB  - Interferon-gamma (IFN-gamma) is a key cytokine of T lymphocytes with major
      regulatory functions in the immune system. To determine and compare protein/DNA
      interactions at the native IFN-gamma locus in T cells, we analyzed the human IFN
      gamma promoter by ligation-mediated polymerase chain reaction (LM-PCR)
      techniques. Accordingly, Jurkat T cells and primary CD45RA and CD45R0 CD4+ T cell
      subsets isolated from peripheral blood using immunomagnetic beads were cultured
      and analyzed by LM-PCR. Constitutive and inducible protein/DNA interactions of
      the IFN-gamma promoter in vivo were detected in all T cells tested.
      Interestingly, an inducible footprint between -183 and -196 was consistently
      observed in Jurkat T cells and CD45RA and CD45R0 T helper subsets upon
      stimulation with phorbol 12-myristate 13-acetate+phytohemagglutinin (PMA+PHA)
      that was highly sensitive to treatment with corticosteroids. This novel target
      site, denoted the C-site, was shown by several criteria, including cell
      distribution studies, stimulation experiments, supershift assays, and cross
      competition electrophoretic mobility shift assays to bind the transcription
      factor AP-1. Mutation of the C-site that prevented AP-1 binding to this site was
      sufficient strikingly to reduce inducible promoter activity in primary CD45R0 T
      cells. In summary, the data demonstrate that IFN-gamma gene transcription in
      primary T cells is regulated in vivo at the level of constitutive and inducible
      protein/DNA interactions. We propose a model where basal transcription is
      maintained by binding of various transcription factors to the IFN-gamma promoter,
      whereas PMA+PHA-inducible IFN-gamma transcription in CD45R0 T cells is associated
      with binding of AP-1 to the C-site.

PMID- 9174600
TI  - The HER2/neu-derived peptide p654-662 is a tumor-associated antigen in human
      pancreatic cancer recognized by cytotoxic T lymphocytes.
AB  - The protooncogene HER2/neu encodes a 185-kDa transmembrane protein with extensive
      homology to the epidermal growth factor receptor. It is overexpressed in several
      human cancers of epithelial origin, such as pancreatic cancer. Previously, we
      demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, and
      non-small cell lung cancer recognized a peptide derived from HER2/neu. To
      evaluate whether this HLA-A2-binding peptide is a tumor-associated antigen (TAA)
      in pancreatic cancer, the ability of HER2/neu-reactive CTL to lyse human
      pancreatic carcinoma cells was tested. CTL were generated from tumor-associated T
      lymphocytes from HLA-A2+ HER2/neu+ breast and ovarian cancer patients. All CTL
      recognized autologous and allogeneic HER2/ neu+ tumor cells in an HLA-A2
      restricted fashion. Furthermore, all CTL recognized p654-662 (GP2) derived from
      HER2/neu. These CTL also recognized HER2/neu+ pancreatic cancer cells in an HLA
      A2-restricted fashion. HER2/neu+ HLA-A2- pancreatic cancer were not or only
      poorly lysed. Repeated stimulation of HLA-A2+ PBL from pancreatic cancer patients
      using the HER2/neu-derived peptide resulted in specific recognition of this
      peptide and, more importantly, HER2/neu+ pancreatic tumors in an HLA-A2
      restricted fashion. Autologous HLA-A2+ fibroblasts or HLA-A2+ malignant melanoma
      cells were not recognized. HLA-A2- peptide-stimulated T lymphocytes showed no
      significant cytotoxicity. These results demonstrate that this HER2/neu-derived
      peptide is a shared TAA among several adenocarcinomas including pancreatic
      carcinoma, suggesting a common mechanism of recognition of these human tumors by
      T lymphocytes. The identification of the HER2/neu-derived peptide GP2 as a TAA in
      pancreatic cancer provides an opportunity for the design of novel immunotherapy
      and vaccine strategies.

PMID- 9174601
TI  - Engagement of the B lymphocyte antigen receptor induces presentation of intrinsic
      immunoglobulin peptides on major histocompatibility complex class II molecules.
AB  - By means of the clonotypic variable region, the immunoglobulin (Ig) is a tumor
      specific antigen on B cell neoplasms. We report that engagement of the B cell
      antigen receptor (BcR) promotes presentation of peptides derived from the B
      cell's intrinsic Ig to major histocompatibility complex (MHC) class II-restricted
      T cells. Thus, anti-Ig endowed normal, ex vivo B lymphocytes from H-2d, Ig
      constant heavy chain allotype b (IgCHb) mice with the capacity to stimulate an I
      Ad-restricted T cell clone which recognizes the gamma 2ab 435-451 allopeptide.
      The corresponding self gamma 2aa peptide is cryptic and 6000-fold less antigenic
      than the gamma 2ab allopeptide. Even so, the syngeneic B cell lymphoma A20 which
      expresses surface(s) IgG2aa, was also recognized by the T cells after BcR
      ligation. Thus, anti-Ig triggered the disclosure of a cryptic tumor antigen
      determinant. We propose that autoantigens, by engaging the BcR of self-reactive B
      cells, induce presentation of intrinsic Ig peptides to which the T helper cell
      (Th) repertoire is not tolerant. In this way, B cells with anti-self potential
      may be activated without Th recognition of nominal autoantigen.

PMID- 9174603
TI  - L-selectin is not essential for naive CD4 cell trafficking or development of
      primary responses in Peyer's patches.
AB  - We showed previously that L-selectin-dependent recirculation of naive CD4 cells
      is essential for development of primary responses in peripheral lymph nodes.
      Recent studies suggest that L-selectin is also required for lymphocyte entry into
      gut mucosal lymphoid tissues that include Peyer's patches and mesenteric lymph
      nodes. Here we show that anti-L-selectin antibody, MEL-14, inhibited homing of a
      rigorously purified, homogenous population of naive CD4 cells into both of these
      tissues as well as peripheral lymph nodes, directly demonstrating a role for this
      receptor in regulating entry into gut-associated sites. However, in intact
      animals, treatment with MEL-14 resulted in the loss of naive CD4 cells (CD45RBhi,
      CD44lo from peripheral lymph nodes but not Peyer's patches, whereas mesenteric
      lymph nodes were intermediate in this regard. In mice primed by parenteral
      immunization with keyhole limpet hemocyanin (KLH), primary CD4 responses were
      readily detected in both. Peyer's patches and mesenteric lymph nodes, and were
      not affected by exposure to MEL-14. Indeed, similar frequencies of KLH-specific
      CD4 cells were recovered from both of these tissues irrespective of MEL-14
      treatment. The results indicate that interactions with L-selectin can be
      circumvented to allow entry of naive CD4 cells into Peyer's patches but not
      peripheral lymph nodes.

PMID- 9174602
TI  - Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1
      shift, and changes surface marker expression in venom-allergic subjects.
AB  - The current study was carried out to elucidate the immunoregulatory changes
      induced by venom immunotherapy (VIT) in bee or wasp allergic subjects. All
      subjects included in this study had a history of severe systemic allergic
      reactions to stings of the respective insect as well as positive skin tests with
      the respective venom or venom-specific IgE in the sera. Parameters assessed in
      peripheral blood mononuclear cells (PBMC) before and after initiation of VIT
      (rush therapy reaching a maintenance dose of 100 micrograms venom injected
      subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45RO,
      interleukin (IL)-2 receptor (R) alpha, IL-4R, IL-12R, Fc epsilon RII, CD40, and
      CD40 ligand (CD40L), cells producing interferon (IFN)-gamma and IL-10 after
      stimulation with phorbol 12-myristate 13-acetate + ionomycin in the presence of
      monensin measured by flow cytometry; secretion of IFN-gamma, IL-4, and IL-10
      measured by ELISA (IFN-gamma and IL-10 were additionally measured by PCR), and
      proliferation after stimulation with the respective venom. Significant decreases
      were observed after VIT for proliferative response to venom and venom + IL-4, IL
      4 secretion, Fc epsilon RII, CD40, and CD40L expression. Significant increases
      were observed after VIT for IFN-gamma concerning the amount secreted and the
      number of producing cells, and IL-10, IL-10 was mainly produced by CD4+ cells
      that were negative for IFN-gamma, but some double-positive (IL-10 and IFN-gamma)
      cells were always detected. Addition of blocking anti-IL-10 antibodies, but not
      isotype control antibodies, prevented down-regulation of proliferation (but not
      IL-4 secretion) and further enhanced IFN-gamma secretion after VIT. These data
      indicate that in insect venom allergic subjects, VIT not only induces a rapid
      shift in cytokine expression from Th2 to Th1 cytokines, but also leads to
      induction of the immunosuppressive cytokine IL-10, which may be important for the
      limitation of potentially harmful allergen-specific Th1 responses. The described
      changes in cytokine expression may be responsible for subsequent increases in
      allergen-specific IgG and decreases in IgE production, as well as suppressive
      activity observed in earlier studies.

PMID- 9174604
TI  - CD43 (leukosialin, sialophorin) expression is differentially regulated by
      retinoic acids.
AB  - CD43 (leukosialin, sialophorin), a cell-surface associated mucin that is
      constitutively expressed at high levels on most leukocytes, is thought to be
      involved in cell activation and adhesion. We here provide evidence that the
      vitamin A metabolites all-trans and 13-cis retinoic acid up-regulate CD43 on
      human leukemic (HMC-1) mast cells, as determined by flow cytometry, Western blot
      analysis, and by semiquantitative reverse transcriptase-polymerase chain
      reaction. Enhanced CD43 expression was accompanied by a strong increase in anti
      CD43-mediated, LFA-1-dependent homotypic aggregation of HMC-1 cells,
      demonstrating that newly synthesized CD43 is functionally active in transmitting
      signals across the plasma membrane which result in enhanced cellular adhesion.
      CD43 expression was also enhanced in response to retinoic acids on isolated human
      skin mast cells and human monocytes, but not on cells of the basophilic cell line
      KU-812 and promyelocytic HL-60 cells, indicating that these agents might act in a
      cell-type specific manner. These combined result-point to a novel aspect in the
      regulation of CD43. Possibly, vitamin A metabolites act directly on the CD43
      gene, since putative retinoic acid response elements have been detected within
      its regulatory regions.

PMID- 9174605
TI  - Signals through CD8 or CD4 can induce commitment to the CD4 lineage in the
      thymus.
AB  - Differentiation of thymocytes into mature single-positive T cells is an ordered
      process involving sequential interactions between T cell receptor (TCR), co
      receptors (CD4 or CD8) and their appropriate major histocompatibility complex
      encoded ligands. Precisely how these receptor/co-receptor engagements determine
      lineage commitment is still controversial, but recently it has been suggested
      that quantitative differences in the signal transmitted by co-ligation of CD4
      versus CD8 with TCR might provide the discriminating signal. We examine this
      hypothesis, using bispecific F(ab')2 antibodies to mimic TCR/ co-receptor
      engagement during thymocyte differentiation. These bispecific antibodies lack Fc
      and can engage surface molecules without extensive cross-linking or targeting to
      Fc receptor-bearing cells. We show that TCR/CD3 co-ligation with CD4 induces
      efficient differentiation of mature CD4 lineage cells, irrespective of their TCR
      specificity. Interestingly, TCR/CD3 co-ligation with CD8 also induces maturation
      of CD4 T cells, although less efficiently, but not of CD8 T cells. Thus, although
      the signals delivered by co-ligation of TCR and CD8 appear weaker than from co
      ligation of TCR and CD4, the outcome from either engagement is the same. These
      data suggest that differences in signal intensity alone do not determine lineage
      commitment in the thymus, but that distinct signals are required for CD4 and CD8
      single-positive cell differentiation.

PMID- 9174606
TI  - The human major histocompatibility complex class Ib molecule HLA-E binds signal
      sequence-derived peptides with primary anchor residues at positions 2 and 9.
AB  - Human histocompatibility leukocyte antigen E (HLA-E) and mouse major
      histocompatibility complex (MHC) class Ib antigen, Qa-1, share the same
      substitutions at two normally conserved positions 143 and 147, which are likely
      to affect binding of the C terminus of peptides. Qa-1 is able to bind a peptide
      derived from the leader sequence of H-2 D and H-2 L molecules. We developed a
      peptide binding assay in vitro to compare the binding specificity of HLA-E with
      the mouse MHC class Ib molecule Qa-1. We demonstrate that HLA-E binds, although
      poorly, the peptide which binds to Qa-1 and that it also binds nonamer signal
      sequence-derived peptides from human MHC class I molecules. Using alanine and
      glycine substitutions, we could define primary anchor residues at positions 2 and
      9 and secondary anchor residues at position 7 and possibly 3.

PMID- 9174607
TI  - Expression of class II, but not class I, major histocompatibility complex
      molecules is required for granuloma formation in infection with Schistosoma
      mansoni.
AB  - Previous studies have suggested that granulomatous inflammation in
      schistosomiasis is mediated by CD4+ T helper lymphocytes sensitized to parasite
      egg antigens. However, CD8+ T cells have also frequently been associated with the
      immune response to schistosome eggs. To examine more precisely the role of CD4+
      and CD8+ T cells in the pathology of the schistosomal infection, we used mice
      with targeted mutations in major histocompatibility complex (MHC) class II or
      class I molecules. These mutations lead, respectively, to the virtual absence of
      CD4+ and CD8+ T cells. The results clearly show that schistosome-infected MHC
      class II mutant mice failed to form granulomas around parasite eggs. In contrast,
      infected MHC class I mutant mice displayed characteristic granulomatous lesions
      that were comparable to those in wild-type control mice. Moreover, lymphoid cells
      from MHC class II mutant mice were unable to react to egg antigens with either
      proliferative or cytokine [interferon-gamma, interleukin (IL)-4, IL-10]
      responses; nor were they able to present egg antigens to specifically sensitized
      CD4+ T helper cells from infected syngeneic control mice. By comparison, cells
      from MHC class I mutant mice exercised all these functions in a manner comparable
      with those from wild-type controls. These observations clearly demonstrate that
      schistosomal egg granulomas are mediated by MHC class II-restricted CD4+ T helper
      cells. They also suggest that CD8+ T cells do not become sensitized to egg
      antigens and play little role, if any, in the pathogenesis of schistosomiasis.

PMID- 9174608
TI  - The mechanism of specific prolongation of class I-mismatched skin grafts induced
      by retroviral gene therapy.
AB  - In the present study, we examine the mechanism of specific hyporesponsiveness to
      major histocompatibility complex (MHC) class I-mismatched skin allografts induced
      by retrovirus-mediated gene transfer of an allogeneic class I gene into syngeneic
      bone marrow (BM). Using appropriate congenic recombinant mouse strains, we have
      mapped MHC determinants that are capable of restoring rapid rejection of Kb
      bearing skin grafts. Our results indicate that either a single class I or a
      single class II alloantigen expressed on skin in association with Kb is able to
      restore the rapid rejection of Kb-mismatched skin grafts. These data suggest that
      third-party alloantigens expressed on skin in association with Kb abrogate
      hyporesponsiveness by providing T cell help. Consistent with this interpretation,
      spleen cells from mice reconstituted with Kb-transduced BM were unable to elicit
      a significant anti-Kb cytotoxic T lymphocyte response in vitro unless interleukin
      2 was added to the culture medium. Skin graft survival was also analyzed on B10.
      AKM mice thymectomized 3-4 weeks post-reconstitution with Kb-transduced BM.
      Thymectomy did not result in significantly prolonged survival of B10. MBR skin
      grafts compared to euthymic controls, suggesting that even early after
      reconstitution, intrathymic deletion of Kb-reactive T cells must have been
      incomplete. Taken together, these data suggest that prolongation of skin
      allograft survival in this model is controlled at the level of T cell help.

PMID- 9174609
TI  - Molecular cloning of the mouse proteasome subunits MC14 and MECL-1: reciprocally
      regulated tissue expression of interferon-gamma-modulated proteasome subunits.
AB  - The primary structures of the interferon-gamma-inducible mouse 20S proteasome
      subunit MECL-1 and its alternate homolog MC14 were determined. Northern analysis
      of mouse tissues revealed that MECL-1 mRNA predominantly occurred in thymus,
      lymph nodes, and spleen, whereas small amounts were detected in non-lymphoid
      tissues such as kidney, muscle, and testis. Unexpectedly, probing RNA blots with
      MC14 showed that tissues with high MECL-1 expression contained little MC14 and
      vice versa. A very similar reciprocal tissue expression was subsequently found
      for the homologous subunit pairs LMP2 and delta as well as LMP7 and MB1. The
      subunit protein composition of 20S proteasomes purified from liver, thymus, and
      lung reflected RNA expression. The impact of a regulated reciprocal tissue
      expression is discussed with respect to thymic selection and the induction of
      tolerance in potentially autoreactive T cells.

PMID- 9174610
TI  - Influences on the lifespan of B cell subpopulations defined by different
      phenotypes.
AB  - The turnover of mature and immature B cells defined by a range of cell surface
      markers was investigated by feeding normal or bcl-2-transgenic (bcl-2-Tg) mice 5'
      bromo-2-deoxyuridine (BrdUrd) for up to 6 weeks. In peripheral lymphoid tissue, B
      cells accumulated BrdUrd with a 50% labeling time of 4.3 weeks and a pattern of
      uptake indicative of the presence of both long-lived and short-lived cells. These
      two kinetic populations could be resolved into immature B220lo/heat-stable
      antigen (HSA)hi cells which labeled rapidly, and B220hiHSAlo cells which were
      uniformly long-lived with a half-life of about 6 weeks. During loading and pulse
      chase experiments, BrdUrd uptake by cells within the mature B220hiHSAlo
      population clearly followed an exponential kinetic pattern, suggesting that their
      loss was governed by stochastic processes. Using other surface markers, the long
      lived population could also be defined by high expression of IgD, representing
      cells in the follicular mantle zone of the spleen, and by the phenotype
      IgMhiIgDloHSAlo which most likely represented marginal zone memory B cells. CD23
      expression on B cells did not differentiate well between long and short-lived
      cells. Only about half of newly labeled B cells appearing in the spleen
      progressed to the long-lived compartment, a proportion which was not altered
      significantly in bcl-2-Tg mice. The most likely explanation was that a
      combination of both positive and negative selection was operating at this site
      which was mediated by pathways not regulated by bcl-2. On the other hand,
      overexpression of bcl-2 did result in a two- to threefold increase in the rate of
      appearance of newly labeled B cells in the spleen, consistent with a possible
      role for this protein during early selection events within the bone marrow.
      Selection processes appeared to be very active in young mice during the shaping
      of the B cell repertoire, since B cells from 6-week-old non-Ig mice displayed a
      rapid rate of turnover irrespective of their surface phenotype, and a significant
      population of long-lived cells did not become evident until the mice had reached
      about 12 weeks of age.

PMID- 9174611
TI  - Fibroblast dependency during early thymocyte development maps to the CD25+ CD44+
      stage and involves interactions with fibroblast matrix molecules.
AB  - We have investigated the role of specific components of the thymic stroma during
      development of CD4-8-T cell precursors by separating and reaggregating precursor
      subsets with individual or combinations of stromal cells. We show that while the
      development of CD25+ 44+ precursors is dependent upon a combination of major
      histocompatibility complex (MHC) class II+ thymic epithelial cells and
      fibroblasts, their direct descendants, CD25+ 44- precursors, develop to the CD4+
      8+ stage in the presence of MHC class II+ thymic epithelial cells alone. Thus,
      CD25+ 44+ precursors are the last developmental stage to be dependent upon
      fibroblast support. In addition, while metabolically inactive, 1-ethyl-3-(3'
      dimethylaminopropyl) carbodiimide (ECDI)-treated fibroblasts retain the ability
      to promote T cell development, prior treatment with hyaluronidase abrogates this
      effect, suggesting that fibroblast-associated extracellular matrix components are
      the key elements involved. In support of this, we show that fibroblasts are
      located in cortical regions of the thymus where T cell precursors are known to
      reside, and that these fibroblasts are associated with an extensive extracellular
      matrix not found on thymic epithelial cells. Finally, antibodies to alpha 4
      integrin and CD44 interfere with the efficiency with which CD4+ 8+ cells are
      generated from CD25+ 44+ precursors in reaggregate cultures and also reduce the
      binding of the latter to 3T3 fibroblasts, suggesting these molecules play a role
      in bringing T cell precursors into contact with fibroblast-associated
      extracellular matrix.

PMID- 9174612
TI  - Resistance of cultured peripheral T cells towards activation-induced cell death
      involves a lack of recruitment of FLICE (MACH/caspase 8) to the CD95 death
      inducing signaling complex.
AB  - Phytohemagglutinin-activated peripheral CD95+ T cells (day 1 T cells) are
      resistant to CD95-mediated apoptosis. After prolonged interleukin-2 treatment,
      these T cells become CD95-mediated apoptosis-sensitive (day 6 T cells). To
      elucidate the molecular mechanism of apoptosis resistance, day 1 and day 6 T
      cells were tested for formation of the CD95 death-inducing signaling complex
      (DISC). DISC-associated active Fas-associated DD protein (FADD)-like interleukin
      1 beta-converting enzyme-like protease (FLICE) also referred to as MACH/caspase 8
      was only found in apoptosis-sensitive day 6 T cells. Further-analysis of mRNA and
      protein expression levels of apoptosis-signaling molecules FADD, receptor
      interacting protein, hematopoietic cell protein tyrosine phosphatase, Fas
      associated phosphatase-1, FLICE, bel-2, bcl-xL, and, bax-alpha showed that only
      the expression level of bcl-xL correlated with T cell resistance to CD95-mediated
      apoptosis (day 1 T cells: bcl-xhiL; day 6 T cells: bcl-XloL). In T cells
      activated in vitro, up-regulation of bcl-xL, has previously been correlated with
      general apoptosis resistance. However, the experiments presented suggest that
      resistance to CD95-mediated apoptosis in T cells can also be regulated at the
      level of recruitment of FLICE to the DISC.

PMID- 9174613
TI  - Regulation of transforming growth factor-beta production by interleukin-12.
AB  - The induction of peripheral tolerance following oral antigen administration in
      several autoimmune disease and conventional animal models correlates with the
      production of transforming growth factor-beta (TGF-beta) and T helper type 2
      (Th2) cytokines. The factors regulating TGF-beta production and its relation to
      the Th2 response, however, have not been defined. We demonstrate that the
      systemic administration of antibodies to interleukin (IL)-12 to ovalbumin (OVA)-T
      cell receptor (TCR) transgenic mice fed high doses of OVA, followed by systemic
      OVA challenge, substantially enhances TGF-beta, but not IL-4 production by
      peripheral T cells. Furthermore, we demonstrate in an in vitro T cell
      differentiation model that naive (CD4+/Mel-14hi) OVA-TCR-T cells stimulated with
      OVA-pulsed dendritic cells (DC) produce four- to fivefold higher amounts of TGF
      beta when cultured with anti-IL-12 or anti-interferon-gamma (IFN-gamma). In this
      in vitro system, IL-4 was not required for TGF-beta production by T cells;
      however, it appeared to enhance levels of TGF-beta by promoting the growth of TGF
      beta-producing cells. Our findings demonstrate that IL-12 and IFN-gamma are
      important negative regulators of TGF-beta production both in vivo and in vitro,
      and that their modulation may be of benefit for the treatment of autoimmune
      disorders.

PMID- 9174614
TI  - Mimotopes of polyreactive anti-DNA antibodies identified using phage-display
      peptide libraries.
AB  - Three monoclonal IgG2a anti-DNA polyreactive autoantibodies, derived from lupus
      prone mice (NZB x NZW)F1, were studied by surface plasmon resonance (BIAcore)
      analysis using three different synthetic double-stranded (ds) oligonucleotides of
      25, 30, and 25 base pairs (bp). These monoclonal antibodies (mAb) exhibited
      dissociation rate constants (k(off)), ranging from 0.0001 (mAb F14.6 and F4.1) to
      0.01/s (mAb J20.8) and k(on) ranging from 2 x 10(5) to 2 x 10(6) /M/s. The
      screening of a constrained random peptide library displayed on M13 bacteriophages
      on these mAb allowed the determination of the specific consensus motifs
      (mimotopes) for mAb F14.6 and J20.8, but not for mAb F4.1. No cross-reaction was
      observed between F14.6- and J20.8-specific peptides (and vice versa). Binding of
      all phages selected on F14.6 was inhibited with 700 ng/ml soluble DNA. The
      binding of one group of peptides selected on J20.8 was inhibited by 400 ng/ml
      soluble DNA, of a second group by 2500 ng/ml, while binding of a third group
      could not be inhibited. The determined consensus sequences do not match with
      known sequences. Peptides specific for F14.6 share negative charges and aromatic
      rings that may mimic a DNA backbone, while peptides selected with J20.8 do not
      bear any negative charge, implying a different kind of molecular recognition, for
      example hydrogen or salt bonds. The peptides selected on J20.8 also bind serum
      antibodies from human patients with systemic lupus erythematosus. In addition,
      BALB/c mice immunized with some of the selected phages exhibit high serum titers
      of IgG3 anti-dsDNA antibodies, further supporting the hypothesis that peptide
      epitopes may mimic an oligonucleotide structure.

PMID- 9174615
TI  - Effect of interleukin-10 on dendritic cell maturation and function.
AB  - The main function of dendritic cells (DC) is to induce the differentiation of
      naive T lymphocytes into helper cells producing a large array of lymphokines,
      including interleukin (IL)-2; interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-10.
      The potent immunostimulatory properties of DC develop during a process of
      maturation that occurs spontaneously in vitro. Since IL-10 has been shown to
      inhibit Th1 responses, we determined its effect on DC maturation and accessory
      function. Our data show that DC that have undergone maturation in vitro in the
      presence of IL-10, have an impaired capacity to induce a Th1-type response in
      vivo, leading to the development of Th2 lymphocytes. Their inability to promote
      the synthesis of IFN-gamma seems to correlate with a decreased production of IL
      12, an heterodimeric cytokine necessary for optimal generation of Th1-type cells.
      These results suggest that IL-10 skews the Th1/Th2 balance to Th2 in vivo by
      selectively blocking IL-12 synthesis by the antigen-presenting cells that play a
      role of adjuvant of the primary immune response. The cytokines present in the
      environment at the presentation step may, therefore, determine the class of the
      immune response induced by DC in vivo, i.e. Th0, Th1 and/or Th2.

PMID- 9174616
TI  - Allergen-induced recruitment of Fc epsilon RI+ eosinophils in human atopic skin.
AB  - We have attempted to identify Fc epsilon RI+ eosinophils in cutaneous late-phase
      reaction in atopic subjects biopsied at 6, 24 and 48 h after the injection of
      either allergen or a diluent control. Compared to the diluent sites, allergen
      injected sites had significantly increased numbers of eosinophils, peaking
      between 6 and 24 h, of which approximately 20-30% expressed mRNA for the alpha,
      beta, and gamma chains of Fc epsilon RI, as shown by in situ hybridization. Using
      either a monoclonal or a polyclonal anti-alpha chain antibody, the Fc epsilon RI
      alpha protein also co-localized to approximately 50-80% of eosinophils at all
      time points studied. We also observed a significant correlation (r = 0.89; p =
      0.02) between the numbers of Fc epsilon RI+ (997+)/EG2+ eosinophils and the
      magnitude of the late-phase reaction. Thus, a significant proportion of
      eosinophils infiltrating the site of allergen-induced allergic tissue reactions
      in atopic subjects express Fc epsilon. RI. The findings show that high-affinity
      IgE receptors may play a role in eosinophil secretory processes in vivo.

PMID- 9174617
TI  - Lipopeptide immunization without adjuvant induces potent and long-lasting B, T
      helper, and cytotoxic T lymphocyte responses against a malaria liver stage
      antigen in mice and chimpanzees.
AB  - We have employed a 26-amino-acid synthetic peptide based on Plasmodium falciparum
      liver stage antigen-3 to evaluate improvements in immunogenicity mediated by the
      inclusion of a simple lipid-conjugated amino acid during peptide synthesis.
      Comparative immunization by the peptide in Freund's adjuvant or by the
      lipopeptide in saline shows that the addition of a palmitoyl chain can
      dramatically increase T helper (Th) cell responses in a wide range of major
      histocompatibility complex (MHC) class II haplotypes, to the extent that
      responses were induced in mice otherwise unable to respond to the non-modified
      peptide injected with Freund's adjuvant, and that the increased immunogenicity of
      the lipopeptide led to high and longer lasting antibody production (studied up to
      8 months). B and T cell responses induced by the lipopeptide were reactive with
      native parasite protein epitopes, and a lipopeptide longer than ten amino acids
      was endogenously processed to associate with MHC class I and elicit cytotoxic T
      lymphocyte (CTL) responses. Finally, the lipopeptide was safe and highly
      immunogenic in chimpanzees, whose immune system is very similar to that of
      humans. Our results suggest that relatively large synthetic peptides, carefully
      chosen from pertinent areas of proteins and incorporating a simple palmitoyl
      lysine, can induce not only CTL, but also strong Th and antibody responses in
      genetically diverse populations. Lipopeptides engineered in this way are simple
      to produce and purify under GMP conditions, they are well tolerated by apes, and
      with the enhanced immunogenicity without the need for adjuvant that we report
      here, they offer a quick and relatively low-cost route to provide material for
      human malaria vaccination trials.

PMID- 9174618
TI  - Magnitude of protein tyrosine phosphorylation-linked signals determines growth
      versus death of thymic T lymphocytes.
AB  - Using concanavalin A (Con A) as a multireceptor-reactive agonist, we studied the
      relationship between the growth or death of thymic T lymphocytes and the agonist
      concentration-dependent magnitude of the intracellularly delivered signal. Both
      immature and mature thymic T lymphocytes were subjected to a high concentration
      of Con A-mediated signal for apoptotic cell death. In this model, a number of
      cellular proteins including mitogen activated protein kinases were phosphorylated
      at tyrosine depending on the concentration of Con A. This effect was followed by
      corresponding increase in serine 73 phosphorylation of c-jun and transcription of
      c-fos. DNA fragmentation and cell membrane disruption developed concomitantly
      after stimulation with high concentrations of Con A. The addition of inhibitors
      of protein kinases which completely inhibited the growth of cells stimulated with
      low concentrations of Con A only partially prevented death, and even promoted DNA
      fragmentation of cells stimulated with high concentrations of Con A. The
      dissociated sensitivities of Con A-mediated cell growth and cell death to the
      inhibitors were, however, shown to be due to the different efficiency of
      inhibition of high and low levels of intracellularly delivered signals. The
      results indicate that the magnitude of signaling could be the principal element
      that determines the growth versus death of thymic T lymphocytes.

PMID- 9174620
TI  - Human interdigitating dendritic cells directly stimulate CD40-activated naive B
      cells.
AB  - Human interdigitating dendritic cells (IDC) were isolated from tonsils based on
      their CD40+ lineage-negative expression in situ. Isolated IDC displayed a
      phenotypic profile similar to that of IDC in tonsils and spleen in situ,
      characterized by high-level expression of major histocompatibility complex class
      II, the co-stimulatory molecules B7.1 (CD80) and B7.2 (CD86), expression of the
      late DC maturation marker CD83, and no expression of CD1a, CD13, or CD33. IDC
      also showed weak nonspecific esterase staining and had the ability to induce an
      allogeneic mixed lymphocyte reaction. In this study, we further show that in the
      presence of surrogate activated T cells in the form of CD40 ligation and IL-2,
      IDC enhance the proliferation of naive B cells and induce their differentiation
      into plasma cells producing IgM. Evidence for the anatomical co-localization of
      naive B cells and IDC in the T cell area together with the data obtained in vitro
      implies a role for IDC in the initiation of the extrafollicular reaction.

PMID- 9174619
TI  - Immunoglobulin lambda light chain orphons on human chromosome 8q11.2.
AB  - We have identified two V lambda genes outside the major lambda locus on
      chromosome 22q11.2, and shown that they reside on chromosome 8q11.2. One gene
      (Orphee1), hybridizing strongly to the V lambda probes, was sequenced and found
      to belong to the V lambda 8 family; the other gene (Orphee2) only hybridized
      weakly. Orphee1 was present in all individuals tested (140) from three different
      populations, and was also found in gorillas. We envisage that these genes were
      generated by duplication and translocation of the V lambda 8a gene (and a V
      lambda pseudogene) from the major locus, and that this event occurred before the
      evolutionary divergence of humans and gorillas. As there is no other evidence for
      V lambda genes outside the major locus, it appears that the human lambda locus
      has undergone considerably less evolutionary shuffling than either the human
      light chain kappa locus or the heavy chain locus.

PMID- 9174621
TI  - Partial purification and characterization of a tumor necrosis factor-alpha
      converting activity.
AB  - Tumor necrosis factor (TNF)-alpha is initially synthesized as an extracellular
      membrane-associated 26-kDa protein that is further cleaved at Ala76-Val77 to
      yield the soluble 17-kDa form. Recently, peptide-hydroxamate metalloproteinase
      inhibitors have been reported to block the proteolytic processing of TNF-alpha,
      thus suggesting that the putative TNF-alpha converting enzyme (TACE) is a zinc
      dependent metalloendopeptidase. In this report, we characterize a TNF-alpha
      converting activity (TACA) that cleaves in vitro the human 26-kDa TNF-alpha at
      the physiological processing site. The chromatography steps followed for
      purification and the use of a panel of proteinase inhibitors indicate that the
      enzyme responsible for TACA is a membrane glycosylated metalloendopeptidase which
      is most likely different from the matrix-degrading metalloproteinases. The
      failure of TACA to process a Val77-->Gly77 precursor mutant emphasizes the
      importance of hydrophobic residue at P1' position. In addition, TACA is not able
      to cleave the mouse pro-TNF-alpha and does not catalyze in vitro the processing
      of other transmembrane proteins susceptible to metalloproteinase-mediated
      shedding, such as interleukin-6 or TNF receptors. These studies suggest the
      existence of an enzyme specific for TNF-alpha within the metalloproteinases
      involved in the processing/shedding of a number of cytokines and cytokine
      receptors.

PMID- 9174622
TI  - Stringent thiol-mediated retention in B lymphocytes and Xenopus oocytes
      correlates with inefficient IgM polymerization.
AB  - Thiol-dependent retention mechanisms involving the microsecond chain Cys575
      ensure that only polymeric IgM are secreted. B lymphocytes are unable to
      polymerize IgM and degrade unpolymerized precursors intracellularly. Since
      several non-lymphoid transfectants secrete hexameric IgM, specific mechanism(s)
      inhibiting IgM polymerization/secretion may be active in B cells. Here, we show
      that Xenopus laevis oocytes are also unable to polymerize IgM and retain this
      isotype via Cys575 as efficiently as B cells. The mechanisms and the hierarchy of
      the thiol-dependent pre-Golgi retention are conserved in amphibian oocytes, as
      indicated by the efficient retention of secretory IgA and the slow secretion of
      unassembled J558 lambda chains. We also show that B cells do not lack any
      structural component necessary to polymerize IgM: after retention has been
      weakened by 2-mercaptoethanol, polymerization can occur if oxidizing conditions
      are restored. Since release from retention can result in polymerization,
      stringent retention in B cells and oocytes might be at the basis of their common
      inability to polymerize secretory IgM. Our findings suggest that disulfide
      interchange reactions in the exocytic compartment can be modulated during B cell
      differentiation to control IgM secretion.

PMID- 9174623
TI  - Sox-4 facilitates thymocyte differentiation.
AB  - The mouse Sry-like transcription factor Sox-4 is expressed in thymus, bone
      marrow, and gonads of adult mice. Sox-4-deficient mice die at embryonic day E14
      due to cardiac malformation. In transfer experiments to irradiated recipients, B
      cell development was shown to be severely impaired in Sox-4-deficient progenitor
      cells. However, no drastic effects on T lymphocyte development were noted,
      despite the high level expression of the Sox-4 gene in the thymus of normal mice.
      Here, we report a detailed analysis of T cell development from Sox-4-deficient
      progenitors. Explanted fetal thymic organ cultures (FTOC) of Sox-4-deficient
      thymi yielded 10-50-fold fewer CD4 CD8 double-positive and single-positive cells
      than FTOC of littermates. This effect was T cell-autonomous, since similar
      observations were made when FTOC were performed by culturing of Sox-4-deficient
      progenitors in wild-type thymus lobes. When Sox-4-deficient fetal liver cells
      were injected together with normal cells intrathymically, they did not compete
      efficiently for reconstitution. It is concluded that Sox-4 facilitates thymocyte
      development.

PMID- 9174624
TI  - Cleavage of caspase family members by granzyme B: a comparative study in vitro.
AB  - The aspartase granzyme B is one of the major components of the granules involved
      in cell killing by cytotoxic T lymphocytes. Granzyme B has been shown to activate
      the apoptotic death pathway in the target cell, and this involves activation of
      members of the caspase (CASP) protein family. Therefore, activational cleavage of
      mouse (m) CASP proforms by granzyme B was examined in vitro. CASP can be
      subdivided in the CASP-1 (interleukin-1 beta-converting enzyme; ICE) subfamily,
      the CASP-2 (Ich1) subfamily, and the CASP-3 (CPP32) subfamily. Our results reveal
      that the proforms of the CASP-3 subfamily members mCASP-3 and mCASP-7 are
      hydrolyzed by granzyme B, while proforms of CASP-2 and CASP-1 subfamily members
      are not directly cleaved. Only one CASP-3 subfamily member, pro-mCASP-6, was not
      proteolytically cleaved by granzyme B. These results indicate that two members of
      the CASP-3 subfamily, but no others, become activated by granzyme B.

PMID- 9174625
TI  - Pathogenesis of myasthenia gravis.
AB  - Various studies over the last 25 years in Man and animal models have revealed
      many steps in the pathogenesis of myasthenia gravis (MG) which is now considered
      the classical organ specific, autoantibody mediated and T cell dependent human
      autoimmune disease. Though not a disease entity, MG is associated with
      pathological alterations of the thymus in about 80% of cases. These are described
      here with reference to distinct models of autoimmunization against the
      acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of
      AChR-specific autoantibodies is the result of a classical antigen-driven immune
      reaction that occurs completely inside the thymus and probably involves AChR on
      myoid cells as the triggering (myasthenogenic) antigen. Genetic factors
      contribute essentially to the pathogenesis of this form of MG. In thymoma
      associated MG genetic factors are probably of marginal significance. Neither
      intratumour autoantibody production nor T cell activation seem to occur and the
      AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that
      share epitopes with the AChR and other auto-antigen targets in paraneoplastic MG
      are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T
      cell selection by molecular mimicry. These data support the hypothesis that
      initial steps in the pathogenesis of most MG cases take place within abnormal
      thymic microenvironments, be they inflammatory or neoplastic. Where these initial
      steps occur in MG cases without thymic pathology is not known. Likewise, the
      factors involved in the initial triggering of MG remain enigmatic in all MG
      subtypes.

PMID- 9174626
TI  - Amplification units and translocation at chromosome 17q and c-erbB-2
      overexpression in the pathogenesis of breast cancer.
AB  - Hyperplasia without and with atypia is considered to be a precursor lesion for
      certain breast carcinomas. The cytogenetic events and the molecular pathology
      involved in the multistep process from normal to invasive carcinoma are unknown.
      To characterise the sequence of early genetic abnormalities of chromosome 17q and
      their biological consequences in the pathogenesis of breast cancer, we performed
      immunohistochemistry on 451 breast tissues including 180 normal breast specimens,
      28 hyperplastic lesions without atypia and 44 with atypia, 100 cases of ductal
      carcinoma in situ (DCIS) and 99 cases of invasive ductal carcinoma. We correlated
      the overexpression of the c-ErbB-2 protein, the histological and the recently
      proposed differentiation classification of DCIS with the extent of DCIS. For
      fluorescence in situ hybridisation (FISH) analysis, different probes spanning the
      17q region including the c-erbB-2 gene locus and those which are found adjacent,
      were used. Reverse painting and comparative genomic hybridisation (CGH) were
      performed on several breast cancer cell lines. c-ErbB-2 overexpression was
      observed in only 29% of DCIS and 23% of invasive carcinomas, but not in
      hyperplastic and normal tissue. c-ErbB-2 overexpression is correlated with poor
      differentiation in DCIS but not in invasive carcinoma. In DCIS, there was no
      correlation with the histological subtype classification. The average extent of
      DCIS is significantly increased from 13.81 mm in c-ErbB-2 negative cases to 29.37
      mm in c-ErbB-2 positive cases. The increase was considered to be a possible
      consequence of the overexpression and is probably due to the previously described
      motility enhancing effect of the c-ErbB-2 protein. The histological and
      differentiation classification of DCIS did not correlate with the extent of
      disease. Using FISH, amplified genes at 17q12, always including the c-erbB-2
      gene, were detected in all cases of DCIS and invasive carcinoma with c-ErbB-2
      overexpression. The centromeric region and the NF1 locus, which is located
      between the centromere and c-erbB-2, were not amplified in any of the DCIS and
      invasive breast carcinomas, but co-amplification of the myeloperoxidase gene was
      detected in 3/5 DCIS and 1/5 invasive carcinomas with c-ErbB-2 overexpression. In
      contrast to c-erbB-2, immunohistochemical overexpression of their respective gene
      products was not observed. FISH, reverse painting and CGH show similar amplified
      genes with amplified c-erbB-2 in c-ErbB-2 overexpressing SK-BR-3 and BT474 human
      breast cancer cells. The amplified genes are part of two different amplicons.
      Extensive modifications of the 17q chromosomal region, caused by translocation,
      were also observed in these cell lines. It is concluded that the modifications of
      chromosome 17q, inducing overexpression of c-ErbB-2 protein, occur at the level
      of transition from hyperplasia to DCIS. They are preserved in invasive carcinoma
      with overexpression of c-ErbB-2 protein. This had led to the hypothesis that
      these modifications at 17q may lead to a larger extent of DCIS.

PMID- 9174627
TI  - Immunoreactive p53 and metallothionein expression in duct carcinoma in situ of
      the breast. No correlation.
AB  - Immunocytochemically detectable MT and p53 have been found more commonly in
      comedo DCIS of the breast with high-grade cytology. The aim of this study is to
      confirm these findings and to investigate the relationship between MT and p53 in
      a single large series of cases of DCIS of the breast. To this end, 127 cases of
      DCIS were classified histologically according to architecture, cytonuclear
      differentiation (grade), presence and extent of intraduct necrosis, and using the
      Van Nuys system. Sections were immunostained for p53 and MT (E9) using
      established techniques, and the extent and intensity of staining were assessed
      semi-quantitively. The results confirmed that there was generally more MT and p53
      positivity in poorly differentiated (grade 3) DCIS with extensive necrosis and
      that MT expression was greater in grade 2 lesions than p53 expression. However,
      overall there was no statistically significant correlation between p53 and MT
      staining. The results indicate that MT and p53 overexpression may arise from
      independent mechanisms in early breast neoplasia.

PMID- 9174628
TI  - Detection of karyotype changes in interphase cells: oligonucleotide-primed in
      situ labelling versus fluorescence in situ hybridization.
AB  - Interphase cytogenetics is a rapidly developing technique which is usually
      performed by fluorescence in situ hybridization (FISH). Recently, oligonucleotide
      primed in situ synthesis (PRINS) has become established as a method of labelling
      centromeric regions of chromosomes in metaphase spreads. We tested the
      suitability of PRINS in detecting the exact copy number of chromosomes 1, 3, 7
      and 8 in intact interphase cells of 17 cytological preparations derived from
      normal and neoplastic tissues. Control procedures consisted in preparation of
      metaphase spreads of lymphocytes of healthy donors, conventional cytogenetics in
      some of the specimens, and omission of the primers or Taq polymerase from the
      reaction mixture. All specimens were additionally examined by FISH and analysed
      blind by two experienced observers. Both PRINS and FISH revealed a corresponding
      distribution of hybridization signals for all chromosomes examined in specimens
      of normal bone marrow (n = 5), normal liver cells (n = 5), three samples of acute
      nonlymphocytic leukaemia in which conventional chromosome analyses had shown
      monosomy 7 or trisomy 8, and in four hepatocellular carcinomas that displayed
      trisomy 1. Overall, statistical analysis revealed no significant difference in
      the signal distribution between the two techniques. Our results demonstrate that
      PRINS is as reliable as FISH for detecting chromosome copy numbers in interphase
      nuclei of intact cells. The PRINS method, however, is easier to perform, faster
      and less expensive, holding great potential for future applications in diagnostic
      pathology.

PMID- 9174629
TI  - Expression of the cyclin dependent kinase inhibitor p21WAF1/CIP1 in oesophageal
      squamous cell carcinomas.
AB  - To elucidate the role of CDK inhibitor p21WAF1/CIP1 in human oesophageal squamous
      cell carcinomas, we examined its expression immunohistochemically using
      surgically resected tissues from 25 patients, and have analyzed the relationship
      with alteration of p53 gene (F-SSCP analysis), proliferative activity (Ki-67
      labelling index), frequency of apoptosis (in situ DNA nick end labelling), and
      degree of differentiation. P21 expression was observed in 11 cases (44%) with a
      percentage of positive cells ranging between 1% and 10%. Of the 25 cases, 4 cases
      showed > 5% of positive cells. As for the relationship with p53 gene, all 7 p53
      mutation positive cases were negative for p21 expression, whereas 11 out of 18
      mutation negative cases showed positive for p21 expression. As for the
      relationship with degree of tumour differentiation, 6 out of 8 well
      differentiated type cases showed positive for p21 expression. By contrast, all 8
      cases of poorly differentiated type were negative for p21 expression. Frequency
      of apoptotic cells was significantly higher in p21 positive cases than negative
      cases although Ki-67 labelling index was almost the same regardless of the
      expression of p21. P21 expressing cells were distributed mainly in the middle
      layers of the invading nests, especially around the keratinization, which was
      almost similar to the distribution of apoptotic cells. Our results suggest that
      expression of p21 in human oesophageal squamous cell carcinomas is induced by a
      p53-dependent pathway and affects apoptosis and differentiation of carcinoma
      cells.

PMID- 9174630
TI  - Mixed medullary-follicular carcinoma of the thyroid. A morphological,
      immunohistochemical and in situ hybridization analysis of 11 cases.
AB  - Mixed medullary-follicular carcinomas (MMFC) of the thyroid are rare tumours
      showing the morphological and immunochemical properties of both parafollicular
      and follicular cell lineages. Their recognition is based on a classical WHO
      definition, although several other patterns have been described in recent years.
      We investigated 11 cases of MMFC by immunohistochemistry and in situ
      hybridization (ISH) to analyse the structural features, the immunophenotypic
      profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the
      neoplasm. Histologically, 10 cases had mixed parafollicular and follicular cell
      populations in the primary tumour and 1 only in the lymph node metastasis. All
      cases were immunoreactive for CT (in medullary areas) and TG (in follicular areas
      and also in the solid component of 8/11 cases). These findings were confirmed by
      ISH analysis. Combined ISH and immunostaining showed that most cases had separate
      CT and TG gene expression, although rare cells with concurrent CT and TG gene
      expression were identified in 2 tumours. We conclude that (a) MMFC display
      heterogeneous morphological patterns and are a special type of thyroid tumour
      undergoing divergent differentiation; (b) in MMFC, CT and TG genes are generally
      not simultaneously expressed by the same cell, although dual expression of CT and
      TG was present in rare neoplastic elements; and (c) the origin of MMFC, whether
      they are derived from the ultimo-branchial body or result from neoplastic
      transformation of different cell populations following common oncogenic stimuli,
      is unclear.

PMID- 9174631
TI  - Immunohistochemical analysis of hepatocyte growth factor in human coronary
      atherectomy specimens: comparison with transforming growth factor beta isoforms.
AB  - The expression and localization of hepatocyte growth factor/scatter factor
      (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions
      retrieved by directional coronary atherectomy and compared with the localization
      of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3).
      In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was
      revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was
      significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and
      0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel,
      respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta
      isoforms in these components except in thrombotic tissue. These cells exhibiting
      strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic
      tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls
      in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly
      demonstrated HGF-IR. In contrast, in control coronary arteries obtained at
      autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that
      HGF produced by macrophages play a part in the process of coronary plaque
      formation attributable to thrombus in man.

PMID- 9174632
TI  - Ultrastructural study of human herpesvirus-7 replication in tissue culture.
AB  - Human herpesvirus 7 (HHV-7) was grown in a CD4+ lymphoblastic cell line (SupT1)
      and in cord blood mononuclear cells (CBMC). Virus infection was demonstrated by
      immunohistology with positive control sera, with monoclonal antibodies and by in
      situ hybridization for viral DNA. Cytopathic effects following HHV-7 infection
      generally resemble those after HHV-6 infection but are less pronounced. The
      ultrastructural appearance of HHV-7 and the replicative stages were similar to
      those described by Kramarsky and Sander for HHV-6. There were some minor
      discrepancies, including quite an extensive and space-filling tegument, a
      slightly different structure of the nucleoid, the frequent finding of
      nucleocapsids without any visible core and apparently scarce or delicate spikes
      on the envelope. These differences may suggest HHV-7 rather than HHV-6, but this
      finding needs confirmation. Mature HHV-7 particles measured 170 nm in diameter,
      with nucleocapsids of 90-95 nm and a tegument of about 30 nm.

PMID- 9174633
TI  - Non-Hodgkin lymphoma with exclusive involvement of the heart and the
      gastrointestinal tract.
AB  - An extranodal high-grade B-cell lymphoma, centroblastic type, with exclusive
      involvement of the heart, stomach and small bowel was detected at post-mortem
      examination following the death of an 80-year-old man. Autopsy revealed massive
      cardiomegaly with a total heart weight of 1800 g owing to an intramyocardial
      tumour involving the right ventricle, and multiple mucosal tumour plaques and
      nodules in the stomach and small bowel. The case highlights the difficulties of
      diagnosing cardiac lymphoma clinically even in the presence of a large tumour
      mass.

PMID- 9174634
TI  - The epidemiology of multiple sclerosis.

PMID- 9174635
TI  - Viruses and multiple sclerosis.

PMID- 9174636
TI  - Development of a pan-retrovirus detection system for multiple sclerosis studies.
AB  - INTRODUCTION: Although recent claims implicating HTLV-1 in multiple sclerosis
      (MS) have been refuted, several reports suggest that another, hitherto
      uncharacterised, retrovirus may be involved. We have developed and applied a
      novel PCR-based strategy to explore this possibility. METHODS: Degenerate
      oligonucleotides were used in a semi-nested format to amplify, from reverse
      transcribed RNA, a region of the pol gene which is well conserved amongst all
      known retroviruses. RESULTS: The 'pan-retrovirus' detection system was shown to
      be capable of detecting diverse retroviruses including human lentivirus, human
      oncovirus, simian D-type virus and murine oncovirus. The 'pan-retrovirus'
      technique identified a novel retroviral sequence, designated MSRV-cpol, in the
      serum of an MS patient and also in purified virions from MS patient-derived
      tissue cultures. Sequence comparisons suggest that in the pol gene MSRV is
      related (approximately 75% homology) to the endogenous retroviral element ERV9.
      CONCLUSION: These findings lend further support to the concept of retroviral
      involvement in MS.

PMID- 9174637
TI  - Cell cultures and associated retroviruses in multiple sclerosis. Collaborative
      Research Group on MS.
AB  - Retroviral particles associated with reverse transcriptase (RT) activity in cell
      cultures from MS patients have been reported by different groups. Cell-cultures
      have been used for the study and characterization of the corresponding retroviral
      genome which we have shown is related to ERV9 in the pol region. Previously
      unpublished details of a study with monocyte cultures are presented together with
      observations on leptomeningeal and choroid-plexus cultures. The generation of
      self-transformed cultures after inhibition of interferon, followed by the loss of
      retroviral expression and recurrent apoptosis, is analyzed. Retroviral particles
      with RT-activity are produced in monocyte cultures with an apparent correlation
      with MS disease activity. However, though leptomeningeal and choroid plexus cells
      from MS can be passaged for a limited period, their evolution in vitro is not
      compatible with stable retroviral expression. These culture limitations greatly
      hampered progress on the elucidation of the retroviral genome sequence.

PMID- 9174638
TI  - Possible involvement of endogenous retroviruses in the development of autoimmune
      disorders, especially multiple sclerosis.
AB  - Endogenous retroviruses are normal elements in vertebrate genomes. Many aspects
      concerning these genomic elements are still uncertain. In mice some endogenous
      retroviral sequences seem to be involved in the regulation of immune responses
      and there is even evidence that a retroviral element is responsible for the
      development of an autoimmune disease in a mouse strain. Whether endogenous
      retroviruses also contribute to the development of autoimmune diseases in humans
      is not known, but it is an interesting possibility. Below we briefly review
      endogenous retroviruses as potential etiological factors in autoimmunity and we
      discuss a possible association between MS and endogenous retroviruses on the
      basis of results from our laboratory.

PMID- 9174639
TI  - Expression of endogenous retroviruses in blood mononuclear cells and brain tissue
      from multiple sclerosis patients.
AB  - OBJECTIVES: To compare the expression of endogenous retroviruses in MS patients
      and controls. MATERIAL AND METHODS: Peripheral blood mononuclear cells were
      obtained from 22 MS patients, a corresponding number of matched healthy donors
      and five patients with other central nervous system disease. Also brain specimens
      from MS patients and controls were obtained. Transcripts of various endogenous
      retroviruses in these samples were detected by RNA-PCR. RESULTS: Several
      endogenous retroviral sequences were transcribed in peripheral blood mononuclear
      cells and brain tissue from MS patients as well as controls. A composite
      transcript of an endogenous retrovirus and a zinc finger sequence was more
      frequently found in healthy donors than in MS patients. CONCLUSION: Some
      endogenous retroviruses are normally transcribed in white blood cells and brain
      tissue. The significance of those findings, which concerned the composite
      transcripts of the zinc finger sequence and its associated endogenous retrovirus
      is uncertain.

PMID- 9174640
TI  - Characterization of retroviruses from patients with multiple sclerosis.
AB  - These studies were performed to characterize retroviruses found in cell lines
      spontaneously developed from peripheral blood mononuclear cells (PBMNC) from 6
      multiple sclerosis patients, a patient with progressive myelopathy and a healthy
      control. The cell lines are B-lymphoblastoid and produce Epstein-Barr virus (EBV)
      particles or express EBV proteins. The B-lymphoblastoid cell lines are also
      characterized by production of low, fluctuating amounts of retrovirus. The low
      productivity complicates purification and characterization, but implementation of
      product-enhanced reverse transcriptase (PERT) assays has provided a highly useful
      tool for monitoring retrovirus production. By electron microscopy, the retroviral
      particles appear type-C-like. Functional assays indicate the presence of Pol, Gag
      and Env. Indirect ELISA demonstrates a significant relation between disease
      activity and reactivity towards retroviral peptides. Molecular characterization
      is primarily based on RT-PCR, cloning, sequencing and Northern- or Southern
      analyses. Molecular characterization is continuing.

PMID- 9174641
TI  - The implications of Epstein-Barr virus in multiple sclerosis--a review.
AB  - The objective of this article is to bring together knowledge about Epstein-Barr
      virus (EBV) in relation to multiple sclerosis (MS) in order to evaluate its
      implications in this disease. All MS patients are EBV seropositive, but EBV is
      not normally detected in the brain. EBV can explain many of the epidemiological
      dogmas known in MS. In addition, other studies point towards the involvement of
      EBV in MS. Despite this, other co-actors seem also to be involved. We still need
      to know whether EBV may be an initiating factor in MS or whether it is a factor
      in the pathogenesis. Possible ways of EBV involvement are discussed: direct
      involvement, an autoimmune inducing factor or a transactivating factor. A current
      treatment study of MS patients with a specific herpes antiviral drug may add
      further information to the etiology and pathogenesis of MS.

PMID- 9174642
TI  - Human herpesvirus-6 immunoglobulin G antibodies in patients with multiple
      sclerosis.
AB  - OBJECTIVE: To further investigate a possible correlation between human
      herpesvirus-6 (HHV-6) infection and multiple sclerosis by analyzing the level of
      HHV-6 antibodies in MS patients and healthy controls. MATERIALS AND METHODS: A
      total of 189 serum samples from patients with multiple sclerosis (MS) in
      different disease stages and 190 serum samples from healthy controls matched for
      age and sex were analyzed for HHV-6 antibodies using a competitive ELISA.
      RESULTS: There was no difference between HHV-6 IgG titers in MS patients and
      controls. Two of the controls were seronegative for HHV-6 versus to none of the
      MS-patients. There was no apparent difference in HHV-6 titers from patients in
      different disease stages. CONCLUSION: This study cannot support the theory that
      HHV-6 is a contributing factor to the development of MS, although a
      seroprevalence study like this would not disclose whether a late primary
      infection (in puberty) with HHV-6 might affect the development of MS.

PMID- 9174643
TI  - Human T-cell lymphotropic virus tax and Epstein-Barr virus DNA in peripheral
      blood of multiple sclerosis patients during acute attack.
AB  - OBJECTIVES: A study was performed to determine whether persistent or latent
      viruses are reactivated during the acute attack in relapsing remitting multiple
      sclerosis (MS). MATERIAL AND METHODS: DNA of herpes simplex virus type 1 and 2
      (HSV-1 and -2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), JC virus
      (JCV) and HTLV-I was searched, using nested polymerase chain reaction (PCR), in
      peripheral blood mononuclear cells (PBMCs) collected from 14 MS patients on the
      first day and, twice a week, during an acute attack of the disease. RESULTS:
      Viral DNA was detected, in at least one PBMC sample, in all the patients.
      Interestingly, EBV DNA was found in 42.8% of the patients on the first day, while
      a sharp increase of the HTLV tax-rex DNA frequency (35.7%) was observed on the
      tenth day. CONCLUSIONS: In MS relapse EBV DNA detection is an early, frequent
      event, while the finding of tax-rex, but not of other HTLV-I genomic regions, is
      a secondary phenomenon, suggesting that these two factors could interact in the
      pathogenesis of MS relapses.

PMID- 9174644
TI  - Pathogenesis of chronic progressive myelopathy associated with human T-cell
      lymphotropic virus type I.
AB  - Human T-cell lymphotropic virus type I (HTLV-I) induces a chronic demyelinating
      disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). While only 0.25% of HTLV-I-infected individuals develop HAM/TSP, the
      mechanisms responsible for the progression of an HTLV-I carrier state to clinical
      disease are not clear. In particular, no specific sequence differences have been
      found between HTLV-I recovered from HAM patients and HTLV-I-infected carriers.
      Since CD4 T cells are the major reservoir of the virus, at least three hypotheses
      implicating CD4 T cells directly or indirectly have been proposed: 1) The
      cytotoxic hypothesis predicts that activated and HTLV-I-infected CD4 T cells
      migrate to the CNS and infect resident cells. Cytotoxic CD8 T cells may then
      recognize viral antigens on HTLV-I-infected CNS cells causing a cellularly
      mediated cytotoxic demyelination. 2) The autoimmune hypothesis predicts that
      either (a) virally reactive T cells crossreact with a CNS antigen, or (b) random
      infection of CD4 T cells eventually results in the infection of CNS-autoreactive
      CD4 T cells that, by virtue of the productive HTLV-I infection, become activated,
      expand and migrate to the CNS, where they encounter their antigen. This results
      in a specific immune response and demyelination, as is known to occur in
      experimental autoimmune encephalomyelitis. 3) The bystander damage hypothesis
      does not implicate a specific response against CNS cells. Instead this hypothesis
      suggests that the presence of IFN-gamma-secreting HTLV-I-infected CD4 T cells and
      their recognition by virally specific CD8 T cells in the CNS induce microglia to
      secrete cytokines, such as TNF-alpha, which may be toxic for the myelin.

PMID- 9174645
TI  - [Ca2+]i oscillations and [Ca2+]i waves in rat megakaryocytes.
AB  - ATP activated [Ca2+]i oscillations were measured in single rat megakaryocytes
      using fluorescence ratio microscopy. With increasing ATP concentration the
      duration of the [Ca2+]i oscillations increased, however, there was considerable
      variation from cell to cell in the absolute value of the peak [Ca2+]i and the
      frequency and duration of the oscillations. This variation depended, in part, on
      the level of Fura-2 loading suggesting that megakaryocytes are sensitive to
      buffering of [Ca2+]i by Fura-2. Agents, that increase the level of intracellular
      cGMP (sodium nitroprusside and 8-pCPT-cGMP) or cAMP (prostacyclin, IBMX,
      forskolin and 8-bromo-cAMP) inhibited [Ca2+]i oscillations. Despite the large
      cell to cell variation in the patterns of [Ca2+]i oscillations, reapplication of
      the agents that elevated cAMP or cGMP inhibited the oscillations similarly. Using
      video rate fluorescence ratio imaging we found that the agonist-induced [Ca2+]i
      oscillations were the result of a well-defined [Ca2+]i wave, which spread across
      the cell with an average speed of about 35 microns/s, during the rising phase of
      each oscillatory spike. After reaching a peak, [Ca2+]i decreased uniformly across
      the whole cell during the falling phase of the spike. Analysis of the temperature
      dependence of [Ca2+]i waves showed that the rate of [Ca2+]i decay exhibited a
      strong temperature dependence (Q10 approximately 4), whereas, the rate of rise
      exhibited a weak temperature dependence (Q10 approximately 1.3), suggesting, that
      the rate limiting process for [Ca2+]i wave propagation in rat megakaryocytes is
      the rate of [Ca2+]i diffusion.

PMID- 9174646
TI  - Bradykinin regulates the histamine-induced Ca2+ mobilization via protein kinase C
      activation in human gingival fibroblasts.
AB  - We previously demonstrated that histamine and bradykinin evoke an increase in
      intracellular Ca2+ ([Ca2+]i) in human gingival fibroblasts by using a fluorescent
      Ca2+ indicator Fura-2. In this paper, we further demonstrate the regulation of
      the histamine-induced Ca2+ mobilization by bradykinin. In fibroblasts stimulated
      with bradykinin (1 microM), subsequent stimulation with histamine (100 microM)
      failed to mobilize Ca2+, whereas bradykinin induced an increase in [Ca2+]i in the
      cells pre-stimulated with histamine. The attenuation of the histamine response
      was dependent on the concentration of bradykinin for the first stimulation.
      Histamine also failed to induce the formation of inositol 1,4,5-trisphosphate in
      fibroblasts pretreated with bradykinin. In fibroblasts pretreated with bradykinin
      (1 microM) for 3 min and then washed with fresh medium, the effect of histamine
      on [Ca2+]i quickly returned to the control level. The activation of protein
      kinase C by phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (PMA) elicited a
      marked decrease in histamine-induced Ca2+ mobilization. When the protein kinase C
      activity was inhibited with H7, a protein kinase C inhibitor, or was down
      regulated by pretreatment with PMA for 20 h, the inhibitory effect of PMA on the
      histamine response was relieved. In the fibroblasts pretreated with H7 or PMA for
      20 h, histamine evoked Ca2+ mobilization even after bradykinin stimulation. These
      results suggest that the histamine response is regulated by bradykinin receptor
      activation via the activation of protein kinase C in human gingival fibroblasts.

PMID- 9174647
TI  - Differences in Ca2+ pumping activity between sub-populations of human red cells.
AB  - It has been shown recently that the free Ca2+ content of human red cells rises
      during ageing in vivo. With the aim of determining the mechanisms involved in
      such a change, we have investigated some aspects of Ca2+ homeostasis. Both the
      initial rate of Ca2+ influx and some kinetic parameters of the Ca2+ pump of human
      red cells were studied in light and dense sub-populations obtained through
      stringent, self-formed Percoll gradients. At 37 degrees C and pH 7.4, no
      differences in Ca2+ entry were found. By contrast, either at pH 7.0 or 7.4, the
      maximal Ca2+ extrusion rate of the approximately 10% heaviest cells was one-half
      of the corresponding lighter ones. The results demonstrate that the elevated free
      Ca2+ concentration distinctive of senescent cells, arises from a reduction in
      Ca2+ extrusion capacity during ageing. The possible physiological significance of
      this finding is discussed.

PMID- 9174648
TI  - Time course of calcium transients derived from Fura-2 fluorescence measurements
      in single fast twitch fibres of adult mice and rat myotubes developing in primary
      culture.
AB  - In this study, we applied a method to correct for the altered binding kinetics of
      Fura-2 for Ca2+ in vivo, on Ca2+ fluorescence transients (Ca2+F) measured using
      Fura-2 in single adult fast twitch skeletal muscle fibres of the mouse, which
      exhibit very fast [Ca2+] responses, and rat myotubes developing in culture which
      exhibit slower [Ca2+] responses (rise time [20-80% of peak] of Ca2+F transients:
      1.81 +/- 0.17 ms and 16.14 +/- 2.60 ms, respectively). After correction, the
      [Ca2+] transients (Ca2+C) measured in both the adult mouse fibres and the
      myotubes rose more rapidly (mean rise time of Ca2+C transients: adult mouse
      fibres, 0.76 +/- 0.12 ms; rat myotubes, 8.25 +/- 2.83 ms) and often exhibited a
      Ca2+ spike which exceeded the peak of the Ca2+F transient. In the adult mouse
      fibres, correction increased the mean peak [Ca2+] of the Ca2+F transients by a
      factor of 7 from 0.53 +/- 0.08 microM to 3.76 +/- 0.71 microM. The accuracy of
      the time course of the corrected Ca2+ transients was confirmed by comparison to
      the time course of Ca2+ transients measured with Mag-Fura-5, which had a similar
      mean rise time (0.94 +/- 0.10 ms, t-test, P = 0.80). The more slowly rising Ca2+
      transients measured in the rat myotubes were less affected by the correction
      process, increasing in mean peak [Ca2+] by a factor of only 1.2 from 0.82 +/-
      0.17 microM to 0.97 +/- 0.15 microM. During the decay phase of the Ca2+
      transients elicited in the adult mouse fibres and the myotubes, the corrected
      Ca2+C signal largely followed the unmodified Ca2+F transient. The correction
      process was found to have little effect on Ca2+ transients with rise time values
      greater than 10 ms, which included most of the Ca2+ transients measured in the
      myotubes.

PMID- 9174649
TI  - Mechanisms involved in ATP-evoked Ca2+ oscillations in isolated human granulosa
      luteal cells.
AB  - Using single-cell microfluorimetry, we have shown that ATP evoked repetitive Ca2+
      oscillations in intact Fura-2 loaded human granulosa-luteal cells (hG/LCs) in the
      absence of extracellular Ca2+. Sustained increases in [Ca2+]i required
      extracellular Ca2+ and ATP depleted stores were refreshed by brief (2 min)
      incubation with external Ca2+. Basal [Ca2+]i was unaffected by caffeine (1 mM),
      but 20 mM caffeine inhibited ATP-evoked Ca2+ release in the absence of external
      Ca2+. Thimerosal (10 microM) evoked repetitive Ca2+ spikes, under Ca(2+)-free
      conditions, which fused to form an elevated plateau when external Ca2+ was
      replaced. Thimerosal-induced changes in [Ca2+]i were reversibly inhibited by the
      thiol reducing agent dithiothreitol (1 mM). The periodicity and amplitude of the
      [Ca2+]i oscillations produced by thimerosal and ATP differ. ATP- or thimerosal
      evoked changes in [Ca2+]i were unaffected by dantrolene sodium (10 microM). The
      Ca(2+)-ATPase inhibitor thapsigargin (1 microM) increased [Ca2+]i and attenuated
      subsequent ATP-evoked changes in [Ca2+]i. We conclude that ATP stimulates an
      oscillatory release of Ca2+ from InsP3-sensitive stores in hG/LCs.

PMID- 9174650
TI  - Inhibition of store-dependent capacitative Ca2+ influx by unsaturated fatty
      acids.
AB  - The effects of the unsaturated fatty acids, arachidonic and oleic acid, on the
      influx of Ca2+ activated by depletion of intracellular stores with thapsigargin
      were investigated in various cell types. By using a Ca2+ free/Ca2+ reintroduction
      protocol, we observed that arachidonic acid (2 to 5 microM) inhibited
      thapsigargin-induced rises in cytosolic free Ca2+ ([Ca2+]i) in Ehrlich tumor
      cells, Jurkat T lymphocytes, rat thymocytes, and Friend erythroleukemia and PC12
      rat pheochromocytoma cells. This effect was attributed to the inhibition of Ca2+
      entry, since arachidonate also inhibited thapsigargin-stimulated unidirectional
      entry of the Ca2+ surrogates Ba2+ and Mn2+. In Ehrlich cells, the IC50 for
      arachidonic and oleic acid was 1.2 and 1.8 microM, respectively. The inhibition
      appeared to depend on the ratio [fatty acid]/[cells] rather than on the absolute
      fatty acid concentration. Experiments with [3H]-oleic acid revealed that the
      inhibitory activity was not correlated with cell internalisation and metabolism
      of the fatty acid. The inhibition was reverted by removal of the fatty acid bound
      to cell membrane by fatty acid-free albumin treatment. The unsaturated fatty
      acids had no effect on ATP/ADP cell levels and plasma membrane potential.
      Pharmacological evidence indicated that cell phosphorylation/dephosphorylation
      events, and pertussis toxin-sensitive G proteins were not involved. Other
      amphipathic lipophilic compounds, i.e. 2-bromopalmitic acid, retinoic acid,
      sphingosine, and dihydrosphingosine, mimicked arachidonic/oleic acid as they
      inhibited thapsigargin-stimulated Ca2+ influx in an albumin-reversible fashion.
      These results suggest that physiologically relevant (unsaturated) fatty acids can
      inhibit capacitative Ca2+ influx possibly because they intercalate into the
      plasma membrane and directly affect the activity of the channels involved.

PMID- 9174651
TI  - Inhibition of hepatic inositol 1,4,5-trisphosphate receptor function by ethanol
      and other short chain alcohols.
AB  - The ability of alcohols to regulate InsP3-receptor activity was examined in
      permeabilized hepatocytes. Incubation with 30-300 mM ethanol decreased the
      sensitivity to InsP3 for Ca2+ release, with little effect on the size of the Ca2+
      store that could be released with maximal concentrations of InsP3. Ethanol (300
      mM) increased the EC50 for InsP3 from a control value of 134.0 +/- 13.5 nM to
      220.0 +/- 25.9 nM. Although ethanol also caused a partial depletion of the total
      pool of stored Ca2+, the ethanol-induced shift in InsP3 sensitivity was not
      secondary to this alteration in Ca2+ loading. Partial depletion of the Ca2+
      stores with low doses of ionomycin and thapsigargin did not cause a shift in
      InsP3 sensitivity. Furthermore, measurements of InsP3 receptor channel activity
      using retrograde flux of Mn2+ to quench the fluorescence of Fura-2 within the
      Ca2+ stores demonstrated that ethanol inhibited InsP3-activated channel activity
      in the absence of stored Ca2+. Other short chain alcohols (methanol, 1-propanol
      and 1-butanol) also decreased the efficacy of InsP3 to release Ca2+. Measurements
      of [3H]-InsP3 binding demonstrated that ethanol decreased the total number of
      InsP3 binding sites without changing the KD. The effect of ethanol on InsP3
      binding was apparent in the presence or absence of Ca2+ and was observed when the
      cells were pre-incubated with ethanol at either 37 degrees C or 4 degrees C. The
      initial rate of InsP3-induced Mn2+ quenching of compartmentalized Fura-2 was
      reduced by ethanol at all doses of InsP3. These data suggest that ethanol
      decreases the sensitivity of the intracellular Ca2+ store to release by InsP3, by
      reducing the number of channels that can be activated by InsP3.

PMID- 9174652
TI  - Evaluation of heart rate changes: electrocardiographic versus
      photoplethysmographic methods.
AB  - The heart rate (HR) variation to forced deep breathing (HRDB) and to the Valsalva
      maneuver (Valsalva ratio; VR) are the two most widely used tests of cardiovagal
      function in human subjects. The HR is derived from a continuously running
      electrocardiographic (ECG) recording. Recently, HR derived from the arterial
      waveform became available on the Finapres device (FinapHR), but its ability to
      detect rapid changes in HR remains uncertain. We therefore evaluated HRDB and VR
      derived from FinapHR using ECG-derived HR (ECGHR) recordings as the standard. We
      also compared the averaged HR on Finapres (Finapav) with beat-to-beat Finapres
      (FinapBB) values. Studies were undertaken in 12 subjects with large HR
      variations: age, 34.5 +/- 9.3 (SD) years; six males and six females. FinapBB
      values were superimposable upon ECGHR for both HRDB and VR. In contrast, Finapav
      failed to follow ECGHR for HRDB and followed HRECG with a lag for the VR. To
      evaluate statistically how closely FinapHR approximated ECGHR, we undertook
      regression analysis, using mean values for each subject. To compare the two
      methods, we evaluated the significance of the difference between test and
      standard values. For HRDB, FinapBB reproducibly recorded HR (R2 = 0.998), and was
      significantly (p = 0.001) better than Finapav (R2 = 0.616; p < 0.001). For VR,
      HRBB generated a VR that was not significantly different from the correct values,
      while HRav generated a value that was slightly but consistently lower than the
      correct values (p < 0.001). We conclude that FinapHR reliably records HR
      variations in the beat-to-beat mode for cardiovascular HR tests.

PMID- 9174654
TI  - Impairment of calcitonin gene-related peptide-induced potentiation of cholinergic
      sweat secretion in patients with multiple system atrophy.
AB  - Loss of sweating is a characteristic feature of multiple system atrophy (MSA)
      with autonomic failure, and widespread anhidrosis may lead to hyperthermia and
      collapse in a hot environment. Calcitonin gene-related peptide (CGRP) is present
      in the periglandular nerves around sweat glands and is a strong stimulant of
      methacholine (MCH)-mediated cholinergic sweating. The present study evaluated
      CGRP-related regulation of cholinergic sweating in patients with MSA. CGRP
      induced potentiation of MCH-mediated cholinergic sweating was significantly
      reduced in MSA patients as compared with normal age-matched controls. These
      results suggest that regulation of sweating is extensively affected in MSA as a
      consequence of peptidergic dysfunction.

PMID- 9174655
TI  - Cold caloric microcirculatory reflex disturbance in patients with Parkinson's
      disease.
AB  - The basal skin microcirculatory blood flow and its change in response to a cold
      caloric stimulus (cold water, 5 degrees C, exposure of one foot for 30 s) were
      investigated in nine patients with Parkinson's disease (PD) and nine normal
      subjects (controls). The results revealed a significant (p < 0.001) difference
      between the groups. In the controls there was a strong decrease in the red cell
      flux (RCF) on cold water exposure, while eight of the nine PD patients revealed
      no detectable change in RCF; in one patient only there was a less pronounced
      reaction. It was concluded that the regulation of the microcirculatory blood flow
      was affected in PD patients; the cold caloric reflex was attenuated or absent but
      there was no difference in the basal microcirculatory blood flow compared to
      normal subjects.

PMID- 9174653
TI  - Attenuation of contractile responses to sympathetic co-transmitters in veins from
      subjects with essential hypertension.
AB  - Neuropeptide Y (NPY), noradrenaline (NA) and ATP are cotransmitters of the
      sympathetic nervous system and exert vasocontractile effects. The aim of this
      study was to determine the role of these sympathetic co-transmitters in human
      hypertension. Subcutaneous vessels from 12 patients with essential hypertension
      and 12 matched controls were studied in vitro. Vascular contractile responses to
      NPY, NA, alpha,beta-methylene ATP (alpha,beta-mATP) and potassium were studied in
      isolated arteries and veins (diameter 0.1-1.1 mm) with intact endothelium. The
      dilatory effect of acetylcholine was used to test the endothelial function. There
      was no difference in potency (pD2) or contractile response to NPY, NA or
      alpha,beta-mATP between hypertensive and control arteries. In veins, however, the
      contractile response to NPY was significantly reduced in hypertensives and the
      responses to NA were unchanged. Furthermore, the sensitivity (pD2) to alpha,beta
      mATP was significantly reduced in veins from hypertensives. There was no
      difference in the dilatory response to acetylcholine between the hypertensives
      and the controls, neither in the arteries nor in the veins, indicating that the
      observed changes in vascular reactivity to NPY, NA and alpha,beta-mATP were not
      endothelium-dependent. In conclusion, the postjunctional contractile effect of
      NPY and sensitivity (pD2) to alpha,beta-mATP, co-transmitters of the peripheral
      sympathetic nervous system, are attenuated in veins in essential hypertension.

PMID- 9174656
TI  - Does sympathetic activation blunt nitric oxide-mediated hyperemia in the human
      forearm?
AB  - To determine if the vasodilating substance nitric oxide (NO) interferes with the
      ability of sympathetic nerves to regulate blood flow in humans, forearm blood
      flow (FBF) was measured during brachial artery infusions of acetylcholine (ACh)
      to evoke endothelial NO release, and during infusions of the NO donor
      nitroprusside (NTP) in five healthy volunteers. Sympathetic activity was
      increased by application of lower body suction and antagonized by brachial artery
      infusions of phentolamine. In the control condition, FBF was 2.4 +/- 0.4 ml/100
      ml per min and rose by 16.9 +/- 3.6 ml/100 ml per min during ACh at 16
      micrograms/min and by 17.0 +/- 4.3 ml/100 ml per min at 64 micrograms/min. With
      suction, FBF was 1.7 +/- 0.6 ml/100 ml per min (p < 0.05 versus control) and rose
      by 11.4 +/- 3.2 ml/100 ml per min during ACh at 16 micrograms/min (p < 0.05
      versus control). After phentolamine, FBF was 3.8 +/- 0.5 ml/100 ml per min at
      baseline (p < 0.05 versus control) and the increases in flow with ACh at either
      16 or 64 micrograms/min were identical to control. During the control NTP trial,
      FBF rose by 6.3 +/- 1.1 ml/100 ml per min with NTP at 2.5 micrograms/min and by
      12.1 +/- 1.4 ml/100 ml per min at 10 micrograms/min. Suction blunted and
      phentolamine augmented the increases in flow with NTP by approximately 50% (p <
      0.05). Due to the unexpected results with ACh, the effects of suction and
      pharmacological sympathectomy with both phentolamine and bretylium on ACh
      mediated dilation were evaluated with lower doses of ACh (8 and 32
      micrograms/min) in six additional studies. Again, altered sympathetic activity
      had inconsistent effects on the rise in FBF with ACh administration. The effects
      of altered sympathetic activity on the blood flow responses to NTP indicate that
      sympathetic activity can modulate NO-mediated vasodilation, suggesting that NO
      does not have a major sympatholytic effect in the human forearm. That sympathetic
      activity did not consistently alter ACh-mediated vasodilation suggests that
      vasodilating mechanisms, in addition to NO release, can be activated by arterial
      administration of ACh in the human forearm.

PMID- 9174657
TI  - Reproducibility of exercise-induced modulation of cardiovascular responses to
      cold stress.
AB  - The modulation of cardiovascular responses to the cold pressor test (CPT) as
      produced by exercise was studied in 13 volunteers. The reproducibility of the
      measurements selected for the study, i.e. heart rate (HR), blood pressure (BP),
      blood flow (BF) and skin temperature (ST), was investigated through repeat
      experiments in the fall of 1994 and the winter of 1995. HR was monitored before,
      during and after a 10-min period of bicycling at 70% of reserve HR. BP, cutaneous
      BF and ST were measured before and after exercise. Two CPTs (hand into ice-cold
      water for 1 min) were performed: one preceding exercise and another at 3 min
      after exercise. The results obtained allow us to conclude that in non
      hypertensive volunteers (1) the pronounced cardiovascular responses (ST, BF and
      BP) induced by CPT are reproducible (p > 0.2) when compared to basal level values
      and (2) cardiovascular responses to cold stress are significantly attenuated by
      exercise (p < 0.03). Our study, therefore, supports and validates the use of our
      coupled exercise-CPT method in ongoing epidemiological studies attempting to
      identify individuals at risk for the development of hypertension as well as those
      most likely to benefit from preventative exercise programs.

PMID- 9174658
TI  - Non-invasive continuous arterial pressure, heart rate and stroke volume
      measurements during graded head-up tilt in normal man.
AB  - The haemodynamic effects of head-up tilt (HUT) at different tilt angles were
      investigated non-invasively in eight normal male subjects. Mean arterial pressure
      (MAP; by Ohmeda Finapres 2300), stroke volume (SV) and heart rate (HR; by BoMed
      NCCOM3-R7S) were continuously recorded whilst performing a series of HUTs (55
      degrees, 10 degrees, 20 degrees, 30 degrees and 55 degrees) lasting 3 min each.
      The response to HUT was proportional to the sinc of the tilt angle. The magnitude
      of the response varied between subjects. HUT to 55 degrees resulted in mean (95%
      confidence limits) increases in MAP by 16 (+/-16)% and HR by 11 (+/-24)% and a
      decrease in SV by -25 (+/-22)%. These results were repeatable after 30 min. At
      small tilt angles, i.e. < or = 20 degrees, MAP did not change and HR decreased by
      -3 (+/-4)%. A detailed analysis revealed immediate dynamic (0-30 s), late dynamic
      (30-90 s) and plateau (after 90 s) phases in the response to HUT. In conclusion,
      HUT produces reproducible haemodynamic effects, although differences exist among
      subjects. A detailed analysis of these effects can be successfully performed
      using non-invasive methods.

PMID- 9174659
TI  - Genetic and biochemical analysis of TGF beta signal transduction.
AB  - TGF beta-like ligands are involved in many different developmental processes that
      pattern a variety of tissues in invertebrates and vertebrates. In the last few
      years, rapid progress has been made toward elucidating the developmental roles of
      the TGF beta-like pathways and identifying the novel components involved in
      transducing their signals, particularly the newly discovered Smads. This rapid
      progress has been the result of a synergy between classical genetic approaches
      and biochemical approaches, and this combined approach is likely to propel future
      understanding of the signaling pathway used by TGF beta.

PMID- 9174660
TI  - Bone morphogenetic proteins: an unconventional approach to isolation of first
      mammalian morphogens.
AB  - It is conventional to identify morphogens from fly and frog embryos during
      morphogenesis using gene-screens, subtractive hybridizations, differential
      displays and expression cloning. This information is then extended to mice and
      men. The bone morphogenetic proteins (BMPs) are a family of pleiotropic
      morphogens/cytokines isolated and cloned from the demineralized extracellular
      matrix of adult bone. Thus, BMPs were isolated from mammalian bone by an
      unconventional approach. BMPs initiate the sequential developmental cascade of
      bone morphogenesis in ectopic sites. The pleiotropic effects of BMPs on
      chemotaxis, mitosis and differentiation are based on concentration-dependent
      thresholds. Recent work has demonstrated the critical role of BMPs in pattern
      formation in amphibian and chick limb development. Targeted disruption of gene
      function by homologous recombination has demonstrated the actions of BMPs beyond
      bone in such disparate tissues as kidney, eye, testis, teeth, skin and heart. The
      successful isolation of first mammalian morphogens has laid the foundation for
      the elucidation of molecular signalling during morphogenesis in bones and beyond.

PMID- 9174661
TI  - Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall
      integrity.
AB  - Genetic studies have recently revealed a role for transforming growth factor-beta
      1 (TGF-beta 1) and its receptors (TGF-beta Rs I and II as well as endoglin) in
      embryonic vascular assembly and in the establishment and maintenance of vessel
      wall integrity. The purpose of this review is threefold: first, to reassess
      previous studies on TGF-beta and endothelium in the light of these recent
      findings; second, to describe some of the well-established as well as
      controversial issues concerning TGF-beta and its regulatory role in angiogenesis;
      and third, to explore the notion of "context' with respect to TGF-beta and
      endothelial cell function. Although the focus of this review will be on the
      endothelium, other vascular wall cells are also likely to be important in the
      pathogenesis of the vascular lesions revealed by genetic studies.

PMID- 9174662
TI  - Insulin-like growth factor binding proteins and their role in controlling IGF
      actions.
AB  - The insulin-like growth factor binding proteins (IGFBPs) are a family of six
      proteins that bind to insulin-like growth factor-I and -II with very high
      affinity. Because their affinity constants are between two- and 50-fold greater
      than the IGF-I receptor, they control the distribution of the IGFs among soluble
      IGFBPs in interstitial fluids, IGFBPs bound to cell surfaces or extracellular
      matrix (ECM) and cell surface receptors. Although there are six forms of insulin
      like growth factor binding proteins, most interstitial fluids contain only three
      or four forms, and usually only one or two predominate. The proteins differ
      significantly in their biochemical characteristics, and this accounts for many of
      the differences that have been observed in their biological actions. Several
      different types of protease cleave these binding proteins. Proteolytic cleavage
      generally inactivates the binding proteins or reduces their ability to bind to
      IGF-I or -II substantially. Several cell types have been shown to secrete these
      proteases; therefore, the factors that regulate protease activity can control
      binding protein actions indirectly. Other post-translational modifications, such
      as glycosylation and phosphorylation, have been shown to alter IGF binding
      protein activity. While binding protein actions have been studied extensively in
      vitro, many of the in vivo activities of these proteins remain to be defined.

PMID- 9174663
TI  - Activation of hematopoietic growth factor signal transduction pathways by the
      human oncogene BCR/ABL.
AB  - BCR/ABL is a human chimeric oncogene that causes chronic myelogenous leukemia
      (CML). The BCR/ABL oncogene is generated from the Philadelphia chromosome (Ph)
      translocation, t(9;22)(q34;q11), and creates a constitutively active tyrosine
      kinase. There is clonal expansion of hematopoietic stem cells of several
      different lineages in CML. CML patients in stable phase usually have high white
      blood counts and immature cells of granulocytic lineages. Stable phase CML
      evolves to a more aggressive phase typically within 3.5-5 years, where
      differentiation is blocked and acute leukemia ensues. The transition of CML
      stable phase to blast phase is reflected in the loss of growth factor requirement
      of CML cells and correlates with additional cytogenetic alterations. Some
      biological effects reported in primary CML cells include reduced apoptosis and
      altered adhesion to fibronectin; however, the cells are dependent on
      hematopoietic growth factors. On a molecular level, the BCR/ABL translocation is
      well characterized. However, the actual mechanism of transformation by the
      BCR/ABL oncogene of hematopoietic cells is largely unknown. Enhancement of the c
      ABL tyrosine kinase activity in BCR/ABL appears to be crucial for transformation.
      This tyrosine kinase activity leads to activation of several signal transduction
      pathways that are also utilized by hematopoietic growth factors, including steel
      factor, thrombopoietin, interleukin-3, and granulocyte/macrophage-colony
      stimulating factor. In several model systems, BCR/ABL has overlapping biological
      effects with hematopoietic growth factors, and transformation of hematopoietic
      growth factor-dependent cell lines leads to growth factor independence. In this
      review, we will describe the molecular and biological abnormalities in CML and
      several signal transduction mechanisms utilized by BCR/ABL as compared to
      hematopoietic growth factors.

PMID- 9174664
TI  - The house that Jak/Stat built.
AB  - An international workshop on "Cytokines, Signaling and the Jak/Stat Pathway'
      organized by Peter C. Heinrich of the Klinikum der RWTH Aachen under the auspices
      of DFG-Forschergruppe was held in Aachen, Germany, on 4-5 October 1996. In this
      review David Levy notes that even though some diagrams shown at the meeting
      displayed more arrows than there were meeting participants, remarkable progress
      has been made in the unraveling of the complexities of cytokine signal
      transduction. The central issue in the field of cytokine signaling is
      specificity, and this issue was addressed through experimental results from
      biochemical, molecular, and genetic studies of signal transduction pathways.

PMID- 9174665
TI  - Interferons and cytokines on a grand scale.
AB  - The first joint meeting of the International Cytokine Society and the
      International Society for Interferon and Cytokine Research was held in Geneva on
      6-10 October 1996. In this report, Fran Balkwill and Paula Pitha relate how
      signal transduction, molecular genetics and structural biology have helped to
      provide a unifying focus to presentations dealing with 100+ cytokines and an even
      larger assortment of receptors and associated signal transducers.

PMID- 9174666
TI  - Effects of cell surface ganglioside sialidase inhibition on growth control and
      differentiation of human neuroblastoma cells.
AB  - Gangliosides on the external side of the plasma membrane are important modulators
      of cellular functions. In previous work we had found that in cultured human SK-N
      MC neuroblastoma cells a cell surface sialidase activity specifically cleaved
      terminal sialic acids from gangliosides, leading to a shift from higher
      sialylated species to GM1 and a decrease of GM3. To further elucidate the
      function of the enzyme, we have now examined the consequences of ganglioside
      sialidase inhibition. When present in the culture medium, the ganglioside
      sialidase inhibitors 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en),
      heparin, and heparan sulfate caused dramatic changes in cell behavior. Thus, the
      inhibitors uniformly led to a complete release from contact inhibition of growth,
      and to the loss of the differentiation markers neuron-specific enolase and
      neurofilaments, and a decrease of cyclic AMP. In presence of NeuAc2en, cells that
      normally were spread out evenly and were firmly attached, appeared smaller,
      rounded, and only loosely adherent to the culture vessel. Exogenous addition of
      vibrio cholerae sialidase mimicked the action of the plasma membrane ganglioside
      sialidase by retarding cell proliferation and increasing intracellular
      acetylcholinesterase. That the ganglioside sialidase inhibitors in the culture
      medium indeed affected solely the cell surface enzyme and not also a lysosomal
      sialidase, was demonstrated in an experiment where the desialylation of
      exogenously added radioactive gangliosides was determined in absence and presence
      of NeuAc2en and NH4Cl, an inhibitor of lysosomal function. Taken together, our
      results suggest that the ganglioside sialidase on the surface of SK-N-MC cells is
      responsible for growth control and differentiation in this neuronal cell line.

PMID- 9174667
TI  - Accumulation of sphingolipids in SAP-precursor (prosaposin)-deficient fibroblasts
      occurs as intralysosomal membrane structures and can be completely reversed by
      treatment with human SAP-precursor.
AB  - The degradation of glycosphingolipids takes place in lysosomes by action of
      specific exohydrolases, with the assistance of sphingolipid activator proteins
      (SAPs). Four of the SAPs, SAP-A to -D (also called saposins A to D), are
      synthesized from a single protein, the SAP-precursor (prosaposin). Deficiency in
      this precursor protein, a rare inherited disease in humans, results in the
      storage of sphingolipids with short oligosaccharide head groups within the
      patients' tissues, and electron microscopy revealed the accumulation of large
      multivesicular storage organelles. In this study we analyze the multivesicular
      storage organelles in cultivated fibroblasts from these patients. The results
      support our hypothesis that endocytosis of plasma membrane-derived lipids occurs
      via small intraendosomal and intralysosomal vesicles and membrane structures that
      are then digested within the lysosomes (Sandhoff, K., T. Kolter, Trends in Cell
      Biol. 6, 98-103 (1996). First, we show that the storage compartment consists of
      late endosomes and lysosomes by immunogold labeling for marker proteins of these
      organelles. The transport of endocytosed bovine serum albumin-colloidal gold or
      cationized ferritin into the compartment occurs with the timing expected for
      transport to late endocytic organelles. Second, complementation of the medium of
      the SAP-precursor-deficient fibroblasts with only nanomolar concentrations of
      purified SAP-precursor nearly completely reversed the aberrant accumulation of
      multivesicular structures, thereby abolishing most of the intralysosomal membrane
      structures. Analysis of the sphingolipid pattern of the cells after metabolic
      labeling with [14C]serine reveals that the cells' ability to degrade
      glycosphingolipids is completely restored by feeding of SAP-precursor at the same
      concentrations. This is the first demonstration in vivo that endocytosed SAP
      precursor is processed into functional active SAPs A,- B,- C, and D and that the
      degradation of the vesicular structures within the lysosomes depends on the
      presence of the SAPs. Moreover, these studies suggest that a therapy program
      based on feeding purified SAP-precursor may be valuable in treating the entire
      family of diseases which result from the loss of one or more of the SAPs.

PMID- 9174668
TI  - Caveolae can be alternative endocytotic structures in elicited macrophages.
AB  - The aim of the present study was to identify omega-shaped plasma membrane
      invaginations, abundantly present in the plasma membrane of elicited macrophages,
      as caveolae. We have used an antibody against the major component of the caveolar
      coat (VIP21/caveolin), and the omega-shaped vesicles were found to be labeled
      with anti-VIP21 providing evidence that these structures were really caveolae.
      Filipin that had been shown to affect caveolae was used to investigate the
      possible endocytotic role of these structures in elicited macrophages. When
      caveolae were selectively inhibited by filipin, the rate of both fluid-phase and
      receptor-mediated endocytosis has been decreased. These data together with our
      results obtained from serial sectioning support that in elicited macrophages
      caveolae can pinch off from the plasma membrane and can function as alternative
      carriers in the endocytotic processes of these cells.

PMID- 9174669
TI  - Differences between fluid-phase endocytosis (pinocytosis) and receptor-mediated
      endocytosis in isolated rat hepatocytes.
AB  - To characterize possible differences between the fluid-phase endocytosis
      (pinocytosis) of bovine serum albumin and the receptor-mediated endocytosis of
      asialo-orosomucoid (AOM) in isolated rat hepatocytes, both probes were conjugated
      to radioiodinated tyramine-cellobiose, [125I]TC. The use of these conjugates made
      it possible to measure the uptake and intracellular distribution of the intact
      proteins as well as of their acid-soluble, membrane-impermeant degradation
      products. [125I]TC-albumin was taken up at a very low rate (0.5%/h) compared to
      [125I]TC-AOM (45%/h), suggesting that neither membrane adsorption nor membrane
      permeation compromised its suitability as a fluid-phase marker. Sucrose gradient
      analysis indicated that both probes sequentially entered light endosomes (1.11
      g/ml), dense endosomes (1.14 g/ml) and lysosomes (1.18 g/ml), but [125I]TC
      albumin traversed the endocytic compartments more rapidly than [125I]TC-AOM, and
      was partially degraded intralysosomally already after 15 min. The microtubule
      inhibitor, vinblastine, had a stronger inhibitory effect on the uptake and
      degradation of [125I]TC-AOM (80% and 95%, respectively) than on the uptake and
      degradation of [125I]TC-albumin (50% and 70%, respectively). In the presence of
      vinblastine, [125I]TC-AOM was retained both in light and dense endosomes, whereas
      [125I]TC-albumin was retained in dense endosomes only, suggesting that the early
      steps of fluid-phase endocytosis were less critically dependent on microtubular
      function than the early steps of receptor-mediated endocytosis. A perturbant of
      vacuolar pH, propylamine, inhibited the degradation of both probes strongly (75
      100%), as would be expected from its lysosomotropic effect. Propylamine also
      inhibited endocytic uptake, with a stronger effect on [125I]TC-AOM uptake (95%
      inhibition) than on [125I]TC-albumin uptake (60% inhibition), probably reflecting
      a reduction in endosomal acidity, reduced receptor-ligand dissociation and
      diminished recycling of free asialoglycoprotein receptors to the cell surface in
      addition to a general trapping of membrane in swollen vacuoles. A protein
      phosphatase inhibitor, okadaic acid, strongly (80-100%) inhibited the uptake and
      degradation of both [125I]TC-albumin and [125I]TC-AOM. An inhibitor of lysosomal
      proteinases, leupeptin, strongly suppressed the degradation of both probes and
      moderately reduced the uptake of [125I]TC-AOM, whereas the uptake of [125I]TC
      albumin was unaffected. In contrast, an inhibitor of autophagic sequestration, 3
      methyladenine, reduced both the uptake and degradation of [125I]TC-albumin
      markedly (55% and 75%, respectively), with considerably less effect on [125I]TC
      AOM (25% and 35%, respectively). As autophagy-inhibitory amino acid mixture did
      not share these effects, suggesting that 3-methyladenine may suppress endocytic
      fluid-phase uptake by an autophagy-independent mechanism. Fluid-phase and
      receptor-mediated endocytosis in hepatocytes thus appear to differ with respect
      to uptake mechanisms as well as in the kinetics by which endocytosed material
      traverses the endocytic-lysosomal pathway.

PMID- 9174670
TI  - Endocytosis and retrograde transport of pertussis toxin to the Golgi complex as a
      prerequisite for cellular intoxication.
AB  - The uptake mechanism of pertussis toxin (PT) in CHO and insulin-producing HIT-T15
      cells was studied. By electron microscopy after direct labeling of the toxin with
      gold particles, PT was found to be taken up by receptor-mediated endocytosis. The
      presence of active pertussis toxin in the Golgi complex was shown by subcellular
      fractionation. The importance of the Golgi localization of pertussis toxin for
      the S1-dependent ADP-ribosylation of G-proteins was investigated employing
      Brefeldin A (BFA) treatment to disrupt Golgi structures. Treatment with Brefeldin
      A completely blocked the pertussis toxin mediated ADP-ribosylation of cellular G
      proteins in CHO and HIT-T15 cells, whereas the BFA-resistant MDCK cells were not
      protected. A mutant CHO cell line (V24.1) exhibiting a temperature-sensitive
      Golgi complex could be protected when grown at restrictive conditions. These
      results strongly indicate that retrograde transport to the Golgi network is a
      necessary prerequisite for pertussis toxin mediated ADP-ribosylation of G
      proteins and thus also for cellular intoxication.

PMID- 9174671
TI  - The plant 73 kDa peroxisomal membrane protein (PMP73) is immunorelated to
      molecular chaperones.
AB  - We previously showed via electron microscopic immunocytochemistry that a 73 kDa
      polypeptide was an authentic peroxisomal membrane protein (PMP73) integrated
      exclusively into the boundary membrane of glyoxysomes in cucumber seedlings. In
      this paper we test the hypothesis that this PMP73 is a member of the heat-shock
      70 protein (Hsp70) family by comparing amino acid sequences of cyanogen bromide
      (CNBr)-cleaved polypeptide fragments, immunoreactivities on protein blots, and
      microscopic immunofluorescence within suspension-cultured BY-2 tobacco cells. A
      sequence of eight amino acids (DAVGPEIQ) in PMP73 showed a high degree of
      similarity (up to 88%) with sequences in the same carboxy-terminal region of four
      plant Hsp70 proteins. IgGs affinity purified to PMP73 recognized on blots a
      membrane-bound Hsp72 (in pea cotyledon microsomes) and a cucumber PMP61, the
      latter shown by CNBr cleavage to be a distinct, but immunorelated polypeptide to
      PMP73. Conversely, IgGs specific for tomato Hsc70 (C-terminal half) recognized
      cucumber PMP73, and IgGs specific for cucumber DnaJ homologue (entire protein)
      recognized cucumber PMP61. In BY-2 cells, cucumber PMP73-specific IgGs localized
      only to peroxisomes. Antibodies raised against portions of tomato Hsc70 also
      localized to the BY-2 peroxisomes (as well as to cytosolic proteins).
      Collectively, the data show that authentic cucumber PMPs73 and 61 are
      immunorelated to each another, and that both exhibit selective immunoreactivity
      to IgGs from two classes of molecular chaperones, namely Hsp70 proteins and plant
      DnaJ homologues. They appear to be unique membrane-bound chaperones that likely
      function as part of the peroxisomal protein translocation machinery.

PMID- 9174672
TI  - Cell cycle-dependent translocations of a major nucleolar phosphoprotein, B23, and
      some characteristics of its variants.
AB  - A major nucleolar phosphoprotein, B23, is thought to play several apparently
      unrelated roles and appears to be associated with other cell compartments besides
      the nucleolus. However, characteristic properties of B23 variants still remain to
      be established. Here, we raised a new monoclonal antibody against B23 (20B2) and
      used it to address the issue particularly focusing on the events during mitosis.
      Also, we made an attempt to generalize the data on the cell cycle-dependent
      translocations of B23 by the use of three mammalian cell lines (HeLa, PK, RAMT)
      which were found to be immunoreactive for 20B2. In all the cell strains studied,
      B23 was chiefly located within the nucleolus at interphase, and was associated
      with a few cellular domains during mitosis. They were: the nucleoplasm (at
      prophase before the nuclear envelope breakdown), the cytoplasm (from prometaphase
      until mid telophase), the perichromosomal layer (from prometaphase till early
      telophase), cytoplasmic B23-containing bodies (at anaphase and telophase) and
      prenucleolar bodies, PNBs (at telophase). On Western blots, electrophoretic
      mobility of B23 was found to be the same at G1, S and G2 periods of interphase,
      but became slower at mitosis. In situ and cell extraction experiments showed that
      like the nucleolar B23, B23 of the perichromosomal layer and that of PNBs was
      highly resistant to extraction with Triton X-100, but could be released with
      Triton X-100/RNase A. These findings indicated that these portions of B23 were
      most likely to be associated with RNA. The cytoplasmic B23 was the major
      intracellular variant of B23 during mitosis. It had a slightly lower
      electrophoretic mobility than the perichromosomal B23 and could readily be
      extracted with Triton X-100 without addition of RNase A, a fact indicating that
      the cytoplasmic B23 was mainly in an RNA-free state. Mitosis-like translocations
      of B23 from the nucleolus to the nucleoplasm induced by actinomycin D increased
      its extractability but did not affect the electrophoretic mobility. The
      phosphorylation status of different B23 variants at interphase and mitosis both
      in controls and following the drug, is discussed.

PMID- 9174673
TI  - Heparin-dependent fibroblast growth factor activities: effects of defined heparin
      oligosaccharides.
AB  - Heparin and related molecules have been identified as important participants in
      fibroblast growth factor (FGF) signaling although the mechanisms of action remain
      unclear. We have used heparin oligosaccharides to examine steps in the signaling
      process which could be affected by the polysaccharide. Immobilized FGF-1 and FGF
      2 bound all sizes of oligosaccharides tested, ranging from tetrasaccharide to
      decasaccharide, at physiological salt concentration. Each group of
      oligosaccharide was eluted from the FGF affinity columns in several peaks, and
      larger oligosaccharides showed higher apparent affinity for the immobilized
      growth factors compared to the shorter ones. Heparin hexasaccharides were the
      smallest fragments providing complete protection of FGF-1 and FGF-2 against
      trypsin digestion. Tetrasaccharides, however, were able to provide partial
      protection. The requirement of heparin for ligand-receptor interaction was
      evaluated in receptor binding assays using Sf9 insect cells engineered to
      overexpress different recombinant FGF receptor (FGFR) species including FGFR1
      beta, FGFR1 alpha or FGFR4 at the cell surface. In these assays hexasaccharides
      were the smallest fragments capable of stimulating FGF-receptor interaction. Over
      the range of concentrations examined, neither hexasaccharides nor octasaccharides
      were able to stimulate receptor binding to the level attained by intact heparin.
      In fact, these oligosaccharides interfered with the ability of intact heparin in
      promoting FGF-receptor binding. The presence of both stimulatory and inhibitory
      activities in hexasaccharide and octasaccharide populations could be attributed
      to structural heterogeneity within the oligosaccharide preparations. However,
      similar observations were obtained with "highly-sulfated" structurally
      homogeneous preparations of hexasaccharide and octasaccharide, although these
      molecules generally had greater stimulatory and less inhibitory activity than
      their structurally heterogeneous counterparts. Hexasaccharides were found to be
      the smallest fragments able to potentiate the FGF-1-induced 3T3 cell
      proliferation while their effect on FGF-2 signaling was less clear. These
      observations suggest that heparin can modulate FGF-signaling at several stages
      with different end results.

PMID- 9174674
TI  - Expression and localization of synaptotagmin I in rat parotid gland.
AB  - Synaptotagmins are a gene family of membrane proteins with distinct expression
      patterns. Synaptotagmin I is an abundant protein of the synaptic vesicle membrane
      and was implicated as the Ca2+ sensor in fast responding synapses. Yet, its
      precise role along the synaptic vesicle life cycle is not fully understood. In
      this report we show that synaptotagmin I is not exclusively confined to neuronal
      and neuroendocrine systems, rather, it is also expressed in the exocrine system
      of the parotid gland. The gene for synaptotagmin I was isolated and sequenced
      from rat parotid cDNA. The identity of synaptotagmin I protein was further
      confirmed by several independent antibodies. The protein is exclusively found in
      the membranous fraction of purified granules, similarly to VAMP-2, another major
      integral membrane protein of synaptic vesicles. Synaptotagmin I represents 0.4%
      of the total membrane protein mass of the granule. Using immunoelectron
      microscopy the two proteins were also localized primarily to the granules'
      membranes. These findings suggest that synaptotagmin I which regulates Ca(2+)
      dependent neurotransmitter release also plays a role which is common to all
      secretory organelles-neuronal, endocrine and exocrine. A role for synaptotagmin I
      in integrating signals with protein secretion in the parotid gland is suggested.

PMID- 9174675
TI  - Critical limits to define a lab adverse event during phase I studies: a study in
      1134 subjects.
AB  - OBJECTIVE: The first goal of phase I drug development is the determination of
      maximal tolerated dose, which must be established by case-by-case analysis,
      sometimes using a laboratory adverse event. Since no accurate rule defining lab
      adverse events, has been validated yet, we propose a new "combined method" based
      on combination of two thresholds: inclusion values and magnitude of variation.
      Using this combined method, the label "lab adverse event" is applied if any lab
      value exceeds the inclusion threshold and is associated with a variation from
      baseline exceeding the variation threshold defined from reference change limit.
      Thus, this study aimed to test this combined method on a large healthy volunteer
      population, studied in 19 phase I centres worldwide, and on five lab parameters:
      alanine amino transferase, aspartate amino transferase, alkaline phosphatases,
      creatinine and polymorphonuclear leukocytes. METHODS: The inclusion threshold
      from each center was used. Reference change limits were defined from volunteers
      previously included in comparable studies and were expressed as absolute values:
      increases of 10 IU.l-1 for alanine amino transferase or aspartate amino
      transferase, 15 IU.l-1 for alkaline phosphatases, 15 mumol.l-1 for creatinine and
      a 0.34 10(9).l-1 decrease for polymorphonuclear leukocytes. Comparison between
      the "combined method" and a normal range method was made using positive
      predictive value and a ratio between relevant and irrelevant results. This
      application was implemented in all young healthy volunteers (1134) included in 38
      phase I studies sponsored by Rhone Poulenc Rorer from 1991 to 1993. RESULTS:
      Seventy seven subjects (6.7%) were indicated in final study reports as having a
      lab adverse event (reference group). Of 179 subjects with lab abnormalities
      defined by the normal range method, 77 belonged to the reference group, inducing
      a poor 0.43 positive predictive value. Of ninety subjects with lab adverse events
      defined by the "combined method", seventy-five belonged to the reference group,
      inducing a two-fold higher 0.83 positive predictive value. The combined method
      produced a high ratio of relevant/irrelevant results (5 = 75/15) compared with
      the low ratio (0.76 = 77/102) achieved using the normal range method. CONCLUSION:
      This new "combined method", leading to a better definition of lab adverse event,
      seems an accurate and useful tool for routine case-by-case analysis within phase
      I drug development studies.

PMID- 9174676
TI  - A comparison of two cohort studies evaluating the safety of cisapride:
      Prescription-Event Monitoring and a large phase IV study.
AB  - OBJECTIVE: The results of Prescription-Event Monitoring (PEM) from over 13,000
      patients receiving cisapride are compared with safety data from a large-scale
      clinical study involving nearly 10,000 patients. RESULTS: The clinical study
      population showed a significantly younger age profile than the PEM population and
      excluded patients with serious disease; however, both studies showed similar
      patterns of adverse events. The most common adverse events reported in
      association with cisapride in both studies were diarrhoea, headache, abdominal
      pain, constipation and nausea. Some of these may be attributed to the underlying
      condition rather than the action of the drug. Prompting patients about adverse
      events during a clinical trial assessment appeared to increase the reporting of
      some conditions: for example, diarrhoea was reported more frequently in the
      clinical trial than in the PEM study. CONCLUSION: Both studies showed cisapride
      to be generally safe and well tolerated.

PMID- 9174677
TI  - Carvedilol versus verapamil in chronic stable angina: a multicentre trial.
AB  - OBJECTIVE: In a multicentre, double-blind, parallel group study, the anti-anginal
      and the anti-ischaemic efficacy of 12 weeks of therapy with the vasodilating beta
      adrenoceptor-blocker carvedilol 25 mg b.i.d. was compared with verapamil 120 mg
      t.i.d. METHODS: During a 2-week placebo run-in period, patients were required to
      have two treadmill exercise tests (modified Bruce Protocol) differing by not more
      than 15% with regard to total exercise time (TET). Of 313 patients enrolled, 248
      were randomized and 212 completed the study according to the protocol. RESULTS:
      The primary variable TET was analysed using the Cox Proportional Hazards Model to
      take into account censored values due to the patient stopping the exercise test
      for reasons other than angina. Forty-three per cent of patients allocated to
      carvedilol and 36% to verapamil did not stop with angina at the final visit.
      There was no difference in the TET between the groups, the risk ratio being 1.14
      in favour of carvedilol (90% CI 0.85-1.52). TET increased from 378 s at baseline
      to 436 s at the final visit in the carvedilol group and from 386 to 438 s in the
      verapamil group. Results for time to angina and time to 1 mm ST-segment
      depression were similar. Compared to verapamil, carvedilol significantly reduced
      HR, systolic BP and rate pressure product at peak exercise. Analysis of 48 h
      Holter monitor data showed a greater reduction of HR and PVCs with carvedilol.
      Lown grading improved in both groups. Adverse events were reported by 48% (3.2%
      serious adverse events) of patients taking carvedilol and 58% (5.7% serious
      adverse events) taking verapamil. CONCLUSION: Carvedilol is at least as effective
      as verapamil in the management of chronic stable angina and demonstrated a
      favourable adverse event profile.

PMID- 9174678
TI  - Relationship between plasma fenofibric acid levels and the effect of micronized
      fenofibrate on cholesterol, low-density-lipoprotein cholesterol and
      apolipoprotein B in patients with primary hypercholesterolemia.
AB  - OBJECTIVE: We examined the relationship between plasma levels of fenofibric acid,
      the active metabolite of fenofibrate, and differences in concentrations of plasma
      lipids, in subjects with primary type IIA or IIB hyperlipoproteinemia (HLP).
      SUBJECTS AND METHODS: Twenty-nine patients (13 with type IIA and 16 with type IIB
      HLP) were treated with a single daily 200-mg dose of micronized fenofibrate for 3
      months, after which the plasma levels of fenofibric acid were determined by HPLC
      after an overnight fast. RESULTS: In the type IIA HLP phenotype, statistically
      significant correlations were found between fenofibric acid levels and changes in
      total cholesterol, LDL-C and apo-B at all three control visits, with the highest
      correlation coefficients at V3 visit (total cholesterol r = 0.85. LDL-C r = 0.68,
      apo-B r = 0.85). In type IIB HLP, statistical significance was confirmed only
      when performing an analysis of pooled values for total cholesterol and LDL-C (r =
      0.42, r = 0.34, respectively). The high correlation between plasma fenofibric
      acid levels and its effect on beta lipoprotein changes might reflect the effect
      of fenofibrate on the catabolism of plasma LDL by the LDL receptor, since that
      type of relationship is typical of drugs which directly influence the target
      compartment without an effect on intermediary steps of metabolism. An explanation
      for the different levels of correlations in type IIA and IIB patients might be
      found in their different metabolic defects. The fact that fenofibrate's impact on
      VLDLs is such an important part of its effect on lipoprotein metabolism supports
      the concept that the effect of circulating fenofibric acid is less pronounced on
      the LDL receptor in type IIB HLP.

PMID- 9174679
TI  - Comparison of the antinociception produced by two oral formulations of ibuprofen:
      ibuprofen effervescent vs ibuprofen tablets.
AB  - OBJECTIVE: The aim of this study was to compare the dose-related effects of both
      ibuprofen tablets and ibuprofen effervescent [placebo, 400 and 800 mg ibuprofen
      (Aktren)] on phasic pain. PATIENTS: Twenty volunteers participated in this
      randomized, double-dummy, fivefold crossover study. METHODS: Measurements were
      obtained before and 15, 60 and 240 min after drug administration. Pain was
      produced by CO2 pulses applied to the left nostril. Subjects rated the intensity
      of the painful stimuli by means of a visual analogue scale. In addition,
      chemosomatosensory event-related potentials were recorded. RESULTS: In line with
      previous work, ibuprofen produced a dose-related decrease in pain-related
      potential amplitudes P1N1, indicating its antinociceptive effects. Higher plasma
      concentrations of ibuprofen were reached 15-40 min after administration of the
      effervescent while ibuprofen tablets had a tmax 60-90 min after administration.
      In addition, 60 min after intake of the effervescent a prolongation of the
      latencies of the potentials was observed, possibly reflecting superior
      antinociceptive properties when compared to ibuprofen tablets. In addition, the
      effervescent appeared to have more consistent effects on intensity estimates
      compared to ibuprofen tablets.

PMID- 9174680
TI  - Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II
      receptor antagonist, in man.
AB  - OBJECTIVE: The pharmacokinetics of orally and intravenously administered
      valsartan were determined in two studies. In a first pilot study, three i.v.
      doses of valsartan were given in an ascending manner (5, 10 and 20 mg) to
      evaluate tolerability and basic pharmacokinetics of the i.v. formulation. In a
      second study, the absolute bioavailability of 80 mg valsartan from a capsule and
      a buffered solution was compared with a 20 mg i.v. dose. METHODS: The
      concentrations of valsartan in plasma and urine were measured using HPLC. The
      disposition of valsartan after an i.v. dose was characterized by biphasic decay
      kinetics, with a distribution phase (half-life 1.0 h), followed by a longer
      elimination phase (half-life 9.5 h). The volume of distribution at steady state
      was 16.9 l, and the total body clearance 2.2 l.h-1. 29% of the i.v. dose was
      recovered unchanged in the urine. RESULTS: Plasma levels peaked 2 h after oral
      administration of the 80 mg capsule. Thereafter, plasma levels declined
      biexponentially with a terminal t1/2 of 7.0 h. Cmax was reached 1 h after
      administration of the solution, and t1/2 was 7.5 h. On average 7.3% (capsule) and
      12.6% (solution) of the dose was excreted in the urine as the unchanged drug. The
      fraction of dose absorbed and systemically available after oral administration
      was 0.23 for the capsule and 0.39 for the solution, based on AUC. Absorption
      appeared to follow two first-order processes. The first phase was rapid, with a
      half-life of 0.5 h and 0.9 h for solution and capsule, respectively. The slower
      absorption phase was characterized by a half-life of 6.5 h for the solution and
      3.5 h for the capsule. Most of the drug was absorbed during the period 0.4 h to 3
      h post-dosing, and 90% of the fraction absorbed from the capsule was absorbed
      within 5 h.

PMID- 9174681
TI  - MAO-A inhibition in brain after dosing with esuprone, moclobemide and placebo in
      healthy volunteers: in vivo studies with positron emission tomography.
AB  - OBJECTIVE: The aim of the study was to investigate whether or not esuprone binds
      substantially to MAO-A in the human brain. METHODS: In a randomised double-blind
      placebo-controlled study 16 male healthy volunteers were examined with positron
      emission tomography (PET) with [11C]harmine. Eight of the volunteers were given
      daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg
      moclobemide, and four volunteers were given placebo tablets. PET was performed
      before initiation of a 7-day treatment period. On day 7, one investigation was
      made immediately before administration of the drug, representing 23 h after the
      previous day's treatment for esuprone and 11 h after the last tablets of
      moclobemide. Further investigations were made 4 h and 8 h after the morning dose
      on day 7. RESULTS: PET showed a high degree of binding of [11C]harmine, a high
      affinity ligand for MAO-A, before the start of treatment, and a marked and
      similar reduction after treatment with esuprone and moclobemide. A slight
      tendency for normalisation of enzyme binding was observed at the last time point.
      In the placebo group no change was observed. Plasma kinetics of esuprone showed a
      rapid elimination with a half-life of about 4 h. CONCLUSION: The study
      demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A
      inhibition in the brain at the doses given. This is an illustration of the
      potential of PET to monitor drug effects directly on target biochemical systems
      in the brain in human volunteers, and the possibility of using these data, rather
      than pharmacokinetic data, for the determination of dosing intervals.

PMID- 9174682
TI  - Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype
      polymorphisms.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the disposition
      of fluvoxamine is associated with the CYP2D6 and CYP2C19 phenotype polymorphisms.
      METHODS: The serum concentration of fluvoxamine was followed for 48 h after oral
      administration of a single dose of 50 mg fluvoxamine to five poor metabolizers of
      the CYP2D6 test drug dextromethorphan, five poor metabolizers of the CYP2C19 test
      drug mephenytoin, and five extensive metabolizers of both test drugs. RESULTS:
      Poor metabolizers of dextromethorphan had significantly higher areas under the
      serum concentration-time curve than extensive metabolizers of dextromethorphan
      (mean 1.31 vs 1.00 mumol.h.l-1). There were no differences between poor and
      extensive metabolizers of mephenytoin (mean, 1.00 vs 1.15 mumol.h.l-1).
      CONCLUSION: The results are consistent with a possible minor to moderate role of
      CYP2D6, but not CYP2C19, in fluvoxamine metabolism.

PMID- 9174683
TI  - Cerebrospinal fluid and plasma disposition of yohimbine and 11-hydroxy-yohimbine
      in young and older healthy subjects, and Alzheimer's disease patients.
AB  - OBJECTIVE: The plasma and cerebrospinal fluid (CSF) disposition of yohimbine (YO)
      and 11-hydroxy-yohimbine (11-OH-YO), after oral administration of a single dose
      of YO (0.65 mg.kg-1) were studied in young and older healthy subjects and in
      patients with Alzheimer's disease (AD). RESULTS: Plasma disposition of YO
      displayed large variability; no significant differences among subject groups were
      observed. In contrast, 11-OH-YO Cmax and AUC were significantly lower in the
      older normal subjects than in the young normal or AD subjects. A strong positive
      correlation between CSF and plasma YO concentrations was observed. A weak
      positive correlation between CSF and plasma concentrations of 11-OH-YO was also
      observed. CSF to plasma concentration ratios for yohimbine and 11-OH-YO were low
      (approximately 2%).

PMID- 9174684
TI  - Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of
      intravenously and orally administered felodipine in healthy men.
AB  - OBJECTIVE: To examine the effect of grapefruit juice on the metabolism of
      felodipine following intravenous and oral administration. METHODS: The study had
      a randomised, four-way, crossover design in 12 healthy males. Single doses of
      felodipine were given as an intravenous infusion for 1 h (1.5 mg) or as an oral
      extended release (ER) tablet (10 mg). Grapefruit juice (150 ml) or water was
      ingested 15 min prior to drug intake. RESULTS: Intake of grapefruit juice did not
      significantly alter the intravenous pharmacokinetics of felodipine compared to
      control treatment, whereas after oral drug administration it did lead to an
      increase in the mean AUC and Cmax by 72% and 173%, respectively, and the mean
      absolute bioavailability was increased by 112%. The fraction of the oral
      felodipine dose reaching the portal system was increased from 45% to 80% when
      intake of drug was preceded by grapefruit juice ingestion. The pharmacokinetics
      of the primary metabolite, dehydrofelodipine, was affected by the intake of
      juice, resulting in a 46% increase in Cmax. Juice intake immediately before oral
      felodipine resulted in more pronounced haemodynamic effects of the drug as
      measured by diastolic blood pressure and heart rate. However, the haemodynamic
      effects of the intravenous administration were not altered by juice intake.
      Vascular-related adverse events were reported more frequently when oral drug
      administration was preceded by juice intake compared with control treatment.
      Taking grapefruit juice immediately prior to intravenous felodipine
      administration did not cause any alteration in the adverse event pattern.
      CONCLUSION: The main acute effect of the grapefruit juice on the plasma
      concentrations of felodipine is mediated by inhibition of gut wall metabolism.

PMID- 9174685
TI  - Interindividual variation in the enzymatic 15-keto-reduction of 13,14-dihydro-15
      keto-prostaglandin E1 in human liver and in human erythrocytes.
AB  - OBJECTIVE: The therapeutic response to PGE1 is highly variable, and a
      contribution by variable formation of its active tertiary metabolite PGE0 is in
      question. Hence, the objective of this study was to assess the person-to-person
      variation of the reduction of the inactive intermediate metabolite 15-KD PGE1 by
      human liver and human erythrocytes in forming the active metabolite PGE0.
      METHODS: Source of enzyme was lysed erythrocytes from 29 donors, and a bank of 37
      donor livers including specimens from 15 children. Tritium-labelled 13,14-dihydro
      15-keto-prostaglandin E1 (15-KD PGE1) was used at low nanomolar concentrations
      and found to be converted almost exclusively to the more polar compound 13,14
      dihydro-prostaglandin E1 (PGE0) by an NADPH-dependent carbonyl reductase. The
      identity of the product PGE0 was established by comparison of its chromatographic
      and mass spectral characteristics with authentic PGE0. RESULTS: Lysed
      erythrocytes had readily measurable enzymatic activity; differences between the
      preparations from 29 subjects were very small with only a twofold range of
      variation. In contrast to lysed erythrocytes, intact erythrocytes did not
      catalyse the reaction so that the erythrocyte activity should be medically
      immaterial. 15-KD PGE1 15-ketoreductase activity of liver cytosol averaged 61.1
      fmol.min-1.mg-1 protein in preparations from 37 human livers. Individual
      activities varied over an almost tenfold range, with indications of a non-normal
      distribution. Kinetic studies of selected specimens showed substantially
      different Vmax values but indistinguishable kM values, suggesting that the
      individual variation in 15-KD PGE1 15-ketoreduction is the result of differences
      in enzyme concentration rather than of structural enzyme variations. The activity
      in 15 livers from children was significantly lower than in those from adults.
      Inhibition data suggest that both the liver and the erythrocyte enzymes belong to
      the class of carbonyl reductases. CONCLUSIONS: The variations in hepatic enzyme
      activity may be expected to affect the transformation of 15-KD PGE1 to the active
      metabolite PGE0 in vivo. The clinical significance remains to be explored.

PMID- 9174686
TI  - Cross-over trials--a commentary.

PMID- 9174687
TI  - Comment on "Pharmacokinetic interaction between cyclosporine and the
      dihydropyridine calcium antagonist felodipine".

PMID- 9174688
TI  - Diabetes insipidus.

PMID- 9174689
TI  - Premature thelarche and precocious puberty.

PMID- 9174690
TI  - Anorexia, bulimia, and exercise-induced amenorrhea: medical approach.

PMID- 9174691
TI  - Anorexia nervosa and bulimia: psychiatric approach.

PMID- 9174692
TI  - Hypothalamic disease: neurosecretory dysfunction and parasellar lesions.

PMID- 9174693
TI  - Hypopituitarism.

PMID- 9174694
TI  - Isolated prolactin deficiency.

PMID- 9174695
TI  - Nonfunctioning pituitary adenoma.

PMID- 9174696
TI  - Craniopharyngioma: transsphenoidal surgery.

PMID- 9174697
TI  - The empty sella.

PMID- 9174698
TI  - Functional hyperprolactinemia.

PMID- 9174699
TI  - Prolactinoma.

PMID- 9174700
TI  - Acromegaly.

PMID- 9174701
TI  - Inappropriate secretion of thyroid-stimulating hormone.

PMID- 9174702
TI  - Gonadotroph adenomas.

PMID- 9174703
TI  - Cushing's: medical approach.

PMID- 9174704
TI  - Cushing's disease: pituitary microsurgery.

PMID- 9174705
TI  - Short stature.

PMID- 9174706
TI  - Growth hormone insensitivity.

PMID- 9174707
TI  - Hyperthyroidism.

PMID- 9174708
TI  - Graves' disease in children.

PMID- 9174709
TI  - Thyroid storm.

PMID- 9174710
TI  - Thyroid ophthalmopathy: surgical management.

PMID- 9174711
TI  - Graves' ophthalmopathy: medical management.

PMID- 9174712
TI  - Primary hypothyroidism.

PMID- 9174713
TI  - Myxedema coma.

PMID- 9174714
TI  - Endemic goiter.

PMID- 9174715
TI  - Childhood primary hypothyroidism and endemic cretinism.

PMID- 9174716
TI  - Diffuse nontoxic and multinodular goiter.

PMID- 9174717
TI  - Single thyroid nodule.

PMID- 9174718
TI  - Thyroiditis.

PMID- 9174719
TI  - Differentiated thyroid carcinoma.

PMID- 9174720
TI  - Medullary thyroid carcinoma.

PMID- 9174721
TI  - Resistance to thyroid hormone.

PMID- 9174722
TI  - Thyroid disease after the sixth decade.

PMID- 9174723
TI  - Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal.

PMID- 9174724
TI  - Adrenal insufficiency.

PMID- 9174725
TI  - Adrenocortical insufficiency in the child.

PMID- 9174726
TI  - Chronic fatigue syndrome.

PMID- 9174727
TI  - Cushing's syndrome.

PMID- 9174728
TI  - Hypoaldosteronism.

PMID- 9174729
TI  - Familial pseudohypoaldosteronism.

PMID- 9174730
TI  - Primary aldosteronism.

PMID- 9174731
TI  - Adrenal carcinoma.

PMID- 9174732
TI  - Nonclassic adrenal hyperplasia.

PMID- 9174733
TI  - Congenital adrenal hyperplasia.

PMID- 9174734
TI  - Glucocorticoid resistance.

PMID- 9174735
TI  - Adrenal incidentaloma.

PMID- 9174736
TI  - Pheochromocytoma.

PMID- 9174737
TI  - Orthostatic hypotension.

PMID- 9174738
TI  - Idiopathic edema.

PMID- 9174739
TI  - Inappropriate antidiuretic hormone secretion.

PMID- 9174740
TI  - Status of endocrine disease with HIV infection.

PMID- 9174741
TI  - The infant with ambiguous genitalia.

PMID- 9174742
TI  - Delayed puberty in girls and primary amenorrhea.

PMID- 9174743
TI  - Occult ovarian failure.

PMID- 9174744
TI  - Infertility in women.

PMID- 9174745
TI  - McCune-Albright syndrome.

PMID- 9174746
TI  - Turner's syndrome.

PMID- 9174748
TI  - Dysmenorrhea.

PMID- 9174747
TI  - Hypermenorrhea and anovulatory cycles in the adolescent.

PMID- 9174749
TI  - Premenstrual syndrome.

PMID- 9174750
TI  - Polycystic ovarian disease.

PMID- 9174751
TI  - Ovarian tumors with endocrine manifestations.

PMID- 9174752
TI  - Endometriosis.

PMID- 9174753
TI  - Perimenopause.

PMID- 9174754
TI  - Combination oral contraceptives.

PMID- 9174755
TI  - Progestin-releasing intrauterine devices.

PMID- 9174756
TI  - Intrauterine devices.

PMID- 9174757
TI  - Implantable contraception.

PMID- 9174758
TI  - Male contraception: ideas for the future.

PMID- 9174759
TI  - Medical abortion.

PMID- 9174760
TI  - Hyperthyroidism in pregnancy.

PMID- 9174762
TI  - Pre-eclampsia and hypertension in pregnancy.

PMID- 9174761
TI  - Diabetes during pregnancy.

PMID- 9174763
TI  - Postpartum thyroid disease.

PMID- 9174764
TI  - Androgen replacement therapy.

PMID- 9174765
TI  - Withdrawal from anabolic steroids.

PMID- 9174766
TI  - Familial male precocious puberty.

PMID- 9174767
TI  - Delayed puberty in boys.

PMID- 9174768
TI  - Gonadotropin therapy of men with hypogonadotropic hypogonadism.

PMID- 9174769
TI  - Hypogonadotropic hypogonadism: gonadotropin-releasing hormone therapy.

PMID- 9174770
TI  - Varicocele.

PMID- 9174772
TI  - Cryptorchidism.

PMID- 9174771
TI  - Male infertility of undetermined etiology.

PMID- 9174773
TI  - Organic erectile dysfunction.

PMID- 9174775
TI  - Androgen-resistance syndromes: considerations of gender assignment.

PMID- 9174774
TI  - Vasectomy and vasectomy reversal.

PMID- 9174776
TI  - 5 alpha-reductase-2 deficiency.

PMID- 9174777
TI  - Germ cell tumors.

PMID- 9174778
TI  - Galactorrhea.

PMID- 9174780
TI  - Gynecomastia.

PMID- 9174779
TI  - Benign breast disease.

PMID- 9174781
TI  - Infant of the diabetic mother.

PMID- 9174782
TI  - Neonatal hypoglycemia.

PMID- 9174783
TI  - Insulin-dependent diabetes in children.

PMID- 9174784
TI  - Insulin-dependent diabetes mellitus in adults.

PMID- 9174785
TI  - Non-insulin-dependent diabetes mellitus.

PMID- 9174786
TI  - Diabetic ketoacidosis and hyperglycemic hyperosmolar coma.

PMID- 9174787
TI  - Definitions, causes, and risk factors for hypoglycemia in insulin-dependent
      diabetes.

PMID- 9174788
TI  - Hypoglycemia of nondiabetic origin.

PMID- 9174789
TI  - Diabetic peripheral neuropathy.

PMID- 9174790
TI  - Diabetic gastrointestinal autonomic neuropathy.

PMID- 9174791
TI  - Diabetic nephropathy.

PMID- 9174792
TI  - Diabetic retinopathy.

PMID- 9174793
TI  - The diabetic foot.

PMID- 9174794
TI  - Infectious complications in diabetic patients.

PMID- 9174795
TI  - Pancreas transplantation as a treatment for diabetes: indications and outcome.

PMID- 9174796
TI  - Insulin allergy and insulin resistance.

PMID- 9174797
TI  - Obesity.

PMID- 9174798
TI  - Hyperlipidemia.

PMID- 9174799
TI  - Clinical prevention of coronary heart disease through cholesterol-lowering
      therapy.

PMID- 9174800
TI  - Genetic rickets and osteomalacia.

PMID- 9174801
TI  - Acquired osteomalacia.

PMID- 9174802
TI  - Renal hypophosphatemic rickets.

PMID- 9174803
TI  - Renal osteodystrophy.

PMID- 9174804
TI  - Hypocalcemia and hypoparathyroidism.

PMID- 9174805
TI  - Hypercalcemia.

PMID- 9174806
TI  - Primary hyperparathyroidism.

PMID- 9174807
TI  - Parathyroid carcinoma.

PMID- 9174808
TI  - Paget's disease of bone.

PMID- 9174809
TI  - Nephrolithiasis.

PMID- 9174810
TI  - Pseudohypoparathyroidism.

PMID- 9174811
TI  - Prostate cancer.

PMID- 9174812
TI  - Benign prostatic hypertrophy.

PMID- 9174813
TI  - Endocrine treatment of breast cancer.

PMID- 9174814
TI  - Endometrial carcinoma and its precursors.

PMID- 9174815
TI  - Gestational trophoblastic disease.

PMID- 9174816
TI  - Gut neuroendocrine tumors.

PMID- 9174817
TI  - General principles of endocrine function after the sixth decade.

PMID- 9174818
TI  - Androgen function after age 50 and treatment of hypogonadism.

PMID- 9174819
TI  - Menopause.

PMID- 9174820
TI  - Sexual function in menopause and postmenopause.

PMID- 9174821
TI  - Systolic hypertension.

PMID- 9174822
TI  - Postmenopausal osteoporosis.

PMID- 9174823
TI  - Growth hormone deficiency in the elderly.

PMID- 9174825
TI  - The management of ovarian cancer: an update.

PMID- 9174824
TI  - Dyslipoproteinemia in the elderly.

PMID- 9174826
TI  - Salvage intraperitoneal therapy of advanced epithelial ovarian cancer: impact of
      retroperitoneal nodal disease.
AB  - PURPOSE: The objective of this study was to evaluate the impact of
      retroperitoneal lymph node disease on the efficacy of salvage intraperitoneal
      (IP) chemotherapy for advanced epithelial ovarian cancer. METHODS: We
      retrospectively reviewed the records of 41 patients with advanced epithelial
      ovarian cancer treated between 9/83-7/95, who had undergone retroperitoneal nodal
      sampling prior to salvage intraperitoneal chemotherapy. RESULTS: Of the 41
      patients treated with debulking surgery and platinum-based chemotherapy, 19 (46%)
      had disease noted in retroperitoneal lymph nodes at initial surgery or at
      reassessment laparotomy, while 22 (54%) had biopsy-proven negative nodes. The
      mean age of the node-positive group was 49 years. Residual disease prior to
      initiation of IP therapy was optimal (< or = 2 cm) in 16 patients and suboptimal
      in 3. Twenty-two patients with a mean age of 55 were found to be node-negative.
      Residual disease prior to initiation of intraperitoneal therapy was optimal (< or
      = 2 cm) in all 22 patients. All patients received salvage intraperitoneal
      chemotherapy. With a median follow-up of 26 months since surgical reassessment,
      the median survival in the node-positive group is 31 months compared to 40 months
      for the node-negative group (p = 0.47). CONCLUSIONS: The presence of
      retroperitoneal nodal disease does not appear to be a contraindication to the use
      of salvage IP chemotherapy in advanced ovarian cancer.

PMID- 9174827
TI  - Prognostic factors in endometrial carcinoma: risk groups and adjuvant
      radiotherapy.
AB  - Prognostic factors for disease-free survival in patients with endometrial
      carcinoma have been retrospectively assessed in 611 cases diagnosed, treated and
      followed at our institution between 1971 and 1990. Age, symptoms, comorbidity,
      FIGO clinical stage, and hysterectomy, as well as size and location of the tumor,
      histologic type, FIGO grade, myometrial invasion, lympho-vascular invasion, and
      final surgical stage have all been evaluated by univariate and multivariate
      methods. A mathematical predictive model has been applied to define risk groups,
      and the applied adjuvant treatments have been evaluated according to these
      groups. One hundred and thirty-one patients were not treated primarily with
      surgery, and the actuarial 5 and 10-year disease-free survival was 51.6% and
      34.7% respectively. Only clinical stage (FIGO 1971) and modality of radiotherapy
      were significant prognostic factors. For the 480 patients treated primarily by
      surgery, independent prognostic factors for 5 and 10-year disease-free survival
      in multivariate analysis were extrauterine spread, absence of diagnostic
      comorbidity, FIGO grades 2-3, lympho-vascular invasion, age > 65 years and
      cervical extension. Five and 10-year disease-free survival was 81.5% and 73.4%
      respectively. Three risk groups were obtained, whose survival was not affected by
      the adjuvant treatments applied.

PMID- 9174828
TI  - Primary serous papillary carcinoma of the peritoneum: a report of 18 patients.
AB  - Eighteen patients with primary papillary serous carcinoma of the peritoneum
      (PPSCP) were treated at the Department of Obstetrics and Gynecology of the
      University of Graz between 1980 and 1996. Primary tumours from other sites,
      particularly the pancreas and ovary, had been excluded. Because of extensive
      spread of the disease particularly in the upper abdomen, seven of the 18 patients
      (38%) underwent exploratory laparotomy only. Median overall survival time was 10
      months (range 1-28+). This figure reflects the extent of spread of the disease at
      diagnosis on one hand, and that optimal cytoreductive surgery (residual disease <
      or = 2 cm) was possible only in six of the 18 patients (33%) on the other. The
      six patients with optimal cytoreduction had a better survival (range 4+ to 28+
      months) than those who underwent less radical surgery. These data indicate, that,
      similar to primary ovarian cancer, the amount of residual disease may be an
      important prognostic factor in patients with PPSCP.

PMID- 9174829
TI  - Weekly cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer:
      a well-tolerated alternative.
AB  - To assess the efficacy and the compliance of weekly cisplatin as neoadjuvant
      chemotherapy in locally advanced cervical cancer, 23 patients, FIGO stage IB-IIA
      > 4 cm-IIB, were recruited. Treatment consisted of four weekly courses of
      cisplatin (1.5 mg/kg): 91% of the patients received the planned therapy without
      dose reduction or delay. Toxicity was mild: delayed emesis was the most common
      side effect. Overall clinical response rate was 85% with a complete response in
      28%. Nineteen patients underwent surgery without any undue increase in morbidity.
      Histologic analysis of surgical specimens revealed a complete response in 25% of
      stage IB-IIA patients; in only one case of stage IIB, was residual parametrial
      involvement present. In conclusion, weekly cisplatin is highly effective, with
      lower cost and less toxicity compared to other neoadjuvant chemotherapy regimens.

PMID- 9174830
TI  - Does an immunoscintigraphy with OC 125 affect the prognosis of ovarian cancer?
AB  - In a retrospective study, a total of 120 ovarian cancer patients were paired in
      terms of staging, grading, patent age, and operative and cytostatic therapy. Half
      of the patients underwent radioimmunoscintigraphy for diagnostic purposes. From
      the point of view of possible adjuvant immunological therapy, we investigated to
      what extent patients with treated ovarian cancer benefit from the application of
      OC 125 in terms of survival time. In our study we have been able to show that at
      favorable stages (FIGO II) the patient benefitted more from a
      radioimmunoscintigraphy than at prognostically unfavorable stages (FIGO IV). Even
      within FIGO stage III we have been able to show, thanks to the large number of
      cases, that patients with an NED situation benefitted significantly more form
      radioimmunoscintigraphy in terms of survival than those with residual tumors.
      Throughout FIGO stage III, patients with radioimmunoscintigraphy showed
      significantly superior 5-year survival rates (p < 0.05) than those without
      radioimmunoscintigraphy. These data would appear to justify prospective studies
      to establish to what extent ovarian cancer patients benefit from an adjuvant
      application of OC 125 in terms of the 5-years survival rate and the relapse-free
      interval.

PMID- 9174831
TI  - Ectopic vaginal decidualization. An unusual finding that presents problems of
      differential diagnosis with carcinoma.

PMID- 9174832
TI  - Carboplatin plus etoposide regimen in advanced breast cancer. A phase II study.
AB  - Carboplatin is used in many kind of tumors with similar results to cisplatin but
      without the same toxicity. We decided to use it, in combination with etoposide,
      for metastatic breast cancer. Eighteen women with advanced breast disease entered
      this phase II study. Each of them received, every 28 days, carboplatin on day 1,
      at a dose calculated with the Calvert formula, and etoposide on days 1, 2, 3 at a
      dose of 100 mg/m2. For 12 women this treatment was the first-line chemotherapy,
      while for the other six it was the second-line therapy, after the administration
      and the failure, in 4 cases out of 6, of regimens based on anthracycline. In each
      group we obtained an objective response of 50%, with a complete response of 25%
      in the first and of 33% in the second. On the whole, 11 patients died (one not
      from the disease) (10/18, 55%). Toxicity was extremely mild, with only one
      patient with grade III anemia. Our data suggest that a carboplatin/etoposide
      combination could be active and well-tolerated in patients with metastatic breast
      cancer, but the few number of patients in this study makes further research
      necessary for confirmation.

PMID- 9174833
TI  - Vaginal intraepithelial neoplasia (VAIN) following hysterectomy in patients
      treated for carcinoma in situ of the cervix.
AB  - OBJECTIVE: To determine the number of patients with carcinoma in situ of the
      cervix treated by hysterectomy who proceeded to develop vaginal intraepithelial
      neoplasia (VAIN) and define whether the subsequent development of VAIN justifies
      intensive cytology and colposcopy follow-up. MATERIALS AND METHODS: Nine hundred
      and ninety-three women who were subjected to hysterectomy with CIN, (793 patients
      had completed 10 years of cytology and colposcopy follow-up) were identified.
      RESULTS: Forty-one patients with VAIN presented with CIN 3 after hysterectomy.
      The upper one half of the vagina was the area more affected. The middle age group
      developed VAIN in the shortest time. Atypical Cells (ASCUS) were found in 42% of
      these patients. Colposcopy revealed VAIN involving the vault angles of the suture
      line in 54% of the cases. In 51% of the cases the grade of vaginal abnormality
      was the same as that of the original lesion in the cervix. CONCLUSION: With such
      data we would propose screening over a 5-year period. Follow-up should also
      include colposcopic review during every examination.

PMID- 9174834
TI  - Uterine sarcoma: a clinicopathological study of 93 cases.
AB  - OBJECTIVE: To evaluate the clinical outcome of patients suffering from primary
      uterine sarcoma diagnosed and treated in our Hospital. SETTING: Department of
      Gynecologic Surgery/Gynecologic Oncology, Hospital Universitario Materno-Infantil
      Vall d'Hebron de Barcelona, Barcelona, Spain. SUBJECTS AND METHODS: A
      retrospective review from 1967 to 1995 of clinical and pathological
      characteristics of 93 patients with primary uterine sarcoma was done. Patients
      were staged using the 1988 FIGO histological classification for uterine cancer.
      Clinical features, type of surgery, adjuvant therapy, recurrences, distant
      metastasis, and survival were recorded. RESULTS: Our study included three main
      histologic types: 44 patients with leiomyosarcoma, 26 patients with endometrial
      stromal sarcoma, and 18 patients with mixed Mullerian sarcomas. The mean age for
      all patients was 54.8 years, and the most common symptom was vaginal bleeding.
      Other clinicopathological features were examined. Although surgery was the most
      frequent treatment, adjuvant therapies have been analyzed and discussed. The
      overall three-year survival rate was 67.9% and the overall five-year survival
      rate was 64.5%. We found statistical differences (p < 0.001) between the stage I
      survival rate and other stage survival rates. CONCLUSIONS: Uterine sarcoma is an
      uncommon neoplasia diagnosed in the 6th decade of life. Leiomyosarcoma is the
      most frequent histologic type (47.3%). Stage I uterine sarcoma has a better
      prognosis than other stages.

PMID- 9174835
TI  - Frequency of HPV infection and GSH levels in plasma of women with cervical
      dysplasia.
AB  - Human papillomavirus (HPV) can be a cause of cervical intraepithelial neoplasia
      (CIN) and cervical cancer. The level of antioxidant compounds in plasma (retinol,
      alfa-tocoferol, vitamins C and E, glutathione) can modulate the progression of
      latent HPV infection to subclinical lesions and CIN. Our studies show that in the
      cases of HPV infection glutathione (GSH) content decreased, but glutathione
      disulfide (GSSG) levels increased. The quantitative GSH/GSSG ratio reflects the
      above changes of both peptides which, the more distinct, the greater the
      pathological changes in the uterine cervix.

PMID- 9174836
TI  - The prognostic significance of second-look laparotomy in advanced ovarian cancer.
AB  - The value of prognostic parameters in predicting the outcome of second look
      laparotomy (SLL) and survival after SLL was assessed in a series of 115 FIGO III
      and IV ovarian cancer patients. The prognostic parameters included age of
      patients, FIGO-stage, differentiation of tumour, maximum diameter of residual
      disease following the initial operation and clinical, cytologic and histologic
      results of SLL. No statistically significant difference was found between stage
      III and IV patients concerning the results of SLL (p = 0.99) and the same is true
      for the tumour differentiation (p = 0.1) and the age of the patient when first
      operated (p = 0.15). On the contrary, residual disease following the initial
      operation is shown to be prognostically significant (p = 0.001). As for the
      overall survival time, the amount of residual tumour after the SLL is shown to be
      the most important parameter (p = 0.0002).

PMID- 9174837
TI  - Quantitative pathology in uterine smooth muscle tumours: the case for the
      standard histologic classification criteria.
AB  - A number of nuclear morphometric factors (longest and shortest axis, perimeter,
      area, roundness coefficient) as well as the number of mitoses per 20 high power
      fields with an x40 objective (mitotic index) and the volume corrected mitotic
      index (VCMI) have been assessed in 33 uterine smooth muscle tumours (14
      leiomyomata, 5 leiomyosarcomata, 9 atypical leiomyomata and 5 tumours of
      uncertain malignant potential). Multivariate analysis showed the VCMI and nuclear
      roundness coefficient to be the two most significant prognostic factors
      achieving, by means of Fisher's linear discriminant function, a high percentage
      of correct reclassification of the tumours into their respective groups.
      Furthermore, VCMI was shown to be a more accurate prognostic factor than the
      simple mitotic index. The results uphold the traditional classification
      histologic criteria and demonstrate the significance of VCMI as a reliable index
      of mitotic activity.

PMID- 9174838
TI  - Complications of pelvic and para-aortic lymphadenectomy in patients with
      endometrial cancer.
AB  - The International Federation of Gynecology and Obstetrics (FIGO) changed the
      staging criteria for endometrial cancer in 1988 and adopted a surgical
      pathological staging involving also pelvic and/or para-aortic lymphadenectomy. A
      total of 236 patients were treated for endometrial adenocarcinoma at Department B
      of the Gynecologic and Obstetrics Institute, University of Turin, between January
      1976 and December 1995. Our protocol for surgical staging always entails pelvic
      and para-aortic lymphadenectomy and a simple total hysterectomy and bilateral
      adnexectomy with removal of the upper third of the vagina. The aim of this study
      was to carry out a retrospective evaluation of the morbidity in patients with
      endometrial cancer after surgical treatment, either TAH-BSO alone or TAH-BSO with
      pelvic and para-aortic lymphadenectomy.

PMID- 9174839
TI  - Is vulvoscopy a reliable diagnostic technique for high grade vulvar
      intraepithelial neoplasia?

PMID- 9174840
TI  - Scanning force microscopy for imaging biostructures at high-resolution.

PMID- 9174841
TI  - Cytochemical localization of phenol-oxidizing enzymes in lignifying Coleus blumei
      stems.
AB  - The cytochemical localization of the phenol oxidases, laccase and peroxidase, has
      been studied in pro-lignifying and lignifying Coleus blumei stem sections using 4
      methoxy-alpha-naphthol as substrate. The results illustrated that, for short
      incubation times, both pro-lignifying and lignifying Coleus sections showed H2O2
      dependent phenol oxidase (peroxidase-like) activity in epidermal and vascular
      tissues, while no detectable H2O2-independent phenol oxidase (laccase-like)
      activity was found in Coleus tissues. For long incubation times, H2O2-independent
      phenol-oxidases can also be detected in these tissues, however, this is probably
      due to the partial capability of intercellular washing fluid Coleus peroxidase to
      oxidize 4-methoxy-alpha-naphthol in the absence of exogenously added H2O2. This
      illustrates not only the importance of the substrate used, but also the
      importance of the incubation time, in the cytochemical localization of phenol
      oxidizing enzymes.

PMID- 9174842
TI  - Distribution of GABA-immunoreactive nerve cells in the bed nucleus of the stria
      terminalis in male and female rats.
AB  - The distribution of GABA-immunoreactive neurons in the subnuclei of the rat bed
      nucleus of the stria terminalis (BST) was studied by means of GABA
      immunohistochemistry. For detection of GABA immunoreactivity we used polyclonal
      antibodies and silver intensification. We have compared the pattern of
      distribution of immunoreactive cells in male and female rats and found some
      sexual difference, that may underlie functional variety. Computer assisted
      quantitative analysis of GABA-immunoreactive neurons per mm2 showed statistically
      significant sex differences in the medial part of the BST (0.001 < P < 0.01). The
      difference in the BST as a whole was set at 0.05 < P < 0.1. Females had more
      numerous GABA-immunoreactive cells than males. The measuring of sex differences
      was done using double-tailed Student's t-test after submitting the data to ANOVA.

PMID- 9174843
TI  - The gastro-enteric-pancreatic neuroendocrine system in two reptilian species:
      Chalcides chalcides and Zoonosaurus madascariensis (Sauridae).
AB  - The presence, localization and distribution of some regulatory peptides and
      serotonin were investigated by single and double immunohistochemical methods in
      the digestive system of two reptiles, Chalcides chalcides and Zonosaurus
      madascariensis. Both immunoreactive (IR) cells and nerve elements were
      demonstrated, showing different distributions according to the antisera tested.
      Similar results were observed in the two saurian species. Chromogranin-SPI-,
      serotonin-, somatostatin14-, pancreatic polypeptide (PP)-, and gastrin-IR cells
      were present along the gut epithelium. Cholecystokinin (CCK)-, and insulin-IR
      cells seemed to be more concentrated in the intestinal portion, while very few
      glucagon containing cells were observed. Bombesin-IR cells were found in the
      stomach and they constituted the only endocrine cells of the closed type in the
      gut. Vasoactive intestinal polypeptide (VIP)-, insulin-, and bombesin-IR nerve
      terminals were also seen. In the pancreatic duodenal portion of Z madascariensis,
      the insulin-, glucagon-, PP-, and somatostatin 14-IR cells were present as single
      elements or grouped in endocrine islets showing a typical topographical
      distribution. By double immunohistochemical techniques, chromogranin-SPI was
      found co-localized with the serotonin- and somatostatin-immunoreactivity, but CCK
      IR cells were always negative to chromogranin-SP1 antiserum. The present work
      demonstrates that the chromogranin antiserum is not useful for identifying all
      the gut endocrine cell types; furthermore, the presence of insulin
      immunoreactivity in the endocrine cells is confirmed, and, for the first time,
      insulin-immunoreactivity is shown in reptilian gut nerve fibres.

PMID- 9174844
TI  - Study of the distribution of glycosidic residues in eccrine sweat glands, with
      special reference to the content of sialic acid.
AB  - We used a group of lectins (Con-A, WGA, SBA, DBA, RCA-1, UEA-1), enzymes
      (neuraminidase digestion) and conventional histochemical techniques (periodic
      acid-Schiff reaction and reduction-saponification-Schiff reaction) in order to
      detect the presence of glycoproteins rich in sialic and neuraminic acids in the
      human eccrine sweat glands. Using both identification systems, our results showed
      an abundant secretion, rich in C8Oxi-acylated sialic acid.

PMID- 9174845
TI  - Glycoconjugates during the annual sexual cycle in lizard epididymal ductuli
      efferentes: a histochemical study.
AB  - The epididymal ductuli efferentes of the lizard Podarcis sicula campestris De
      Betta are lined with simple, columnar, nonciliated and ciliated cells. The use of
      lectin histochemistry has provided information about changes of sugars associated
      with glycoconjugates of epithelial cells and intraluminal spermatozoa which are
      conveyed from the longitudinal canal to the cranial region of the ductus
      epididymis. Epithelial cells exhibited residues of alpha-D-mannose, N
      acetylglucosamine, and beta-D-galactose-(1-4)-N-acetylglucosamine as revealed
      with lectins Con A, WGA and RCA120, respectively, throughout the sexual cycle. An
      increase of RCA120 staining was observed on microvilli of nonciliated cells and
      in the cytoplasm of ciliated cells during the reproductive period. However,
      during the following refractory period, when the organ was in regression, there
      was a decreased staining with Con A on microvilli and the absorbent surface of
      nonciliated cells, with WGA in nonciliated cells and the cytoplasm of ciliated
      cells, and with RCA120 on microvilli and the cytoplasm of both cell types.
      Terminal alpha-D-galactose residues were increasingly stained from autumn up to
      the reproductive period with BS I-B4 on microvilli, the absorbent surface and
      cilia, whereas they were entirely lacking during the refractory period. UEA I
      revealed alpha-L-fucose residues on the absorbent surface of nonciliated cells
      during the abortive and reproductive periods, increasing in the latter period
      when cilia also expressed this sugar. Terminal alpha/beta-D-N-acetylgalactosamine
      was evidenced with SBA on the absorbent surface of nonciliated cells during the
      reproductive period. The terminal beta-D-galactose-(1-3)-N-acetylgalactosamine
      dimer was never found with PNA, whereas O- and N-linked sialoglycoconjugates were
      present only during the reproductive period. The spermatozoa head exhibited N
      linked glycans with high-mannose content, and beta-D-galactose-(1-4)-N
      acetylglucosamine as well as O- and N-linked sialoglycoconjugates throughout the
      year. During the reproductive period, oligosaccharides with alpha-D-mannose
      residues increased, and oligosaccharides with terminal alpha-D-galactose, alpha-L
      fucose and sialic acid-N-acetylgalactosamine dimer were also present. Unlike
      spermatozoa of seminiferous tubules, the spermatozoa head of the lizard
      epididymal ductuli efferentes exhibited seasonal variability in the lectin
      binding pattern which may be related to time-dependent changes in the
      glycoconjugate profiles of epithelial cells.

PMID- 9174846
TI  - VIP-like immunoreactivity in the intestinal tract of fish with different feeding
      habits.
AB  - We studied the distribution of vasoactive intestinal polypeptide immunoreactive
      (VIP-ir) cells and fibres in the intestine of three fish species with different
      feeding habits: the silver carp (Hypophthalmichthys molitrix), the goldfish
      (Carassius auratus), and the pumpkinseed sunfish (Lepomis gibbosus). Each species
      was divided into two groups: (1) fish fed once a day up until sacrifice and (2)
      fish fed once a day and then fasted three days before sacrifice. Immunoreactive
      endocrine cells and fibres were present in all three fish species. The
      immunoreactive cells were distributed along the entire intestinal mucosa of the
      carp and goldfish but were found only in the anterior intestine of the sunfish.
      The immunoreactive fibres were present along the entire intestinal wall, in the
      myenteric plexus, in the circular muscular layer, and in the connective tissue of
      the mucosa in all three fish species. No differences were found between the cells
      and fibres of normally-fed animals and the cells and fibres of fasted animals.
      The authors hypothesize that the different distributions of VIP-ir cells and
      fibres are related to the different contents of hard and indigestible matter of
      the fish food.

PMID- 9174847
TI  - Plasma levels of beta-endorphin during the menstrual cycle.
AB  - During recent years, many research teams have suggested a possible role of
      endogenous opiates in the control of the menstrual cycle. The level of
      immunoreactive beta-endorphin was measured on different days during the ovulatory
      cycle of 131 healthy volunteers. The levels of luteinizing hormone (LH), follicle
      stimulating hormone (FSH), 17 beta-estradiol and progesterone were also measured.
      The graphic representation of opiate levels during the female menstrual cycle,
      where day O is the day of ovulation, shows that plasmatic beta-endorphin levels
      are not stable throughout. The levels increase progressively during the
      follicular phase, reaching a maximum (mean 139.49 pg/ml, SD 42.23 pg/ml, 95%
      confidence interval 121.22-157.75 pg/ml) 4 days before ovulation. During the
      periovulatory period (days-3 to +3) levels of beta-endorphin are very stable
      (mean day 0, 27.8 pg/ml, SD 6.36 pg/ml, 95% confidence interval 19.29-27.83
      pg/ml) and low (p < 0.05), followed by a renewed increase during the luteal phase
      (mean day + 5, 87.86 pg/ml, SD 36.49 pg/ml) where a maximum level (mean 102.78
      pg/ml, SD 30.35 pg/ml) is reached 24 h before the next menses. The beta-endorphin
      level has a negative correlation with the LH level (r = -0.50, p < 0.001) on the
      preovulatory days, and during the luteal phase a positive linear correlation (r =
      0.47, p < 0.001) is found with the progesterone level. It seems that beta
      endorphin levels in the plasma are influenced by the ovarian steroids. However,
      the influence of the plasmatic opiate on the gonadotropins is currently under
      discussion.

PMID- 9174848
TI  - Reduced meal-related gastrointestinal hormone response to adrenocorticotropic
      hormone stimulation test in female athletes.
AB  - This study was undertaken to elucidate the impact of hypercortisolism in meal
      related gastrointestinal hormone secretion and appetite in female endurance
      athletes. Thirteen elite runners and seven sedentary women participated on two
      occasions, either receiving intravenous injection of 250 micrograms synthetic
      adrenocorticotropic hormone (ACTH) 1-24 or saline. Blood samples were collected
      before and after the injection, and then in connection with a standardized meal.
      Serum concentrations of cortisol, cholecystokinin (CCK), gastrin, insulin and
      glucose were analyzed. Self-ratings of appetite were assessed by visual analog
      scales. Elevated basal levels of cortisol and glucose were found in the athletes.
      ACTH-induced cortisol response was comparable between groups, but a negative
      correlation between basal cortisol levels and the ACTH-induced response was
      found. In sedentary women, ACTH challenge enhanced meal-related CCK and gastrin
      responses, whereas athletes showed a blunted response of these hormones combined
      with decreased satiety and reduced levels of insulin. Blunted meal-related
      response of gastrointestinal hormones and decreased satiety in female runners
      after ACTH stimulation compared to sedentary women are probably due to difference
      in the effect of cortisol, which could be explained by cortisol insensitivity as
      a result of basal hypercortisolism in the athletes. Decreased CCK response and
      satiety in female athletes may reflect increased nutritional requirements.

PMID- 9174849
TI  - Long-term administration of pulsatile gonadotropin-releasing hormone for
      exploration of pituitary functionality in amenorrheic patients.
AB  - Differentiation between hypothalamic and pituitary amenorrhea is generally based
      on the luteinizing hormone-releasing hormone (LHRH) test (whether as a single
      dose, two consecutive doses, or pulsatile over 5-10 days), together with high
      resolution imaging (computed tomography or magnetic resonance) of the sellar
      region. Long-term administration of gonadotropin-releasing hormone (GnRH) is
      generally used only for ovulation induction, and not for diagnostic purposes.
      Here, we report the results of long-term administration of GnRH to 19 women
      initially diagnosed as suffering from hypothalamic amenorrhea on the basis of
      LHRH testing and computed tomography imaging. During treatment, subjects received
      20-micrograms pulses of GnRH every 90 min, subcutaneously from a portable
      infusion pump. Fourteen subjects responded (i.e. ovulated) during the first
      treatment cycle; one subject menstruated but did not ovulate during the first
      cycle, and the dropped out of the study; the remaining four subjects did not
      ovulate or menstruate despite at least three treatment cycles. Magnetic resonance
      imaging of the sellar region of these four subjects revealed pituitary lesions
      (partially empty sella in three cases, microadenoma in one case) which had not
      been detected by computed tomography. By contrast, no such abnormalities were
      detected in the nine responders who agreed to undergo magnetic resonance imaging.
      These findings suggest that long-term administration of GnRH is of value not only
      for ovulation induction but also for diagnostic purposes. Specifically, an
      initial diagnosis of hypothalamic amenorrhea is confirmed if there is a positive
      ovulation response after two GnRH treatment cycles; otherwise, pituitary
      amenorrhea should be suspected. Our results also suggest that magnetic resonance
      imaging is more effective than computed tomography for the detection of partially
      empty sella.

PMID- 9174850
TI  - The behavior of follicle cysts formed after long-acting gonadotropin-releasing
      hormone analog administration in patients with polycystic ovarian syndrome.
AB  - This study was conducted to examine the effect of ovarian cysts that develop
      after administration of a gonadotropin-releasing hormone (GnRH) analog during an
      ovulation induction program for patients with polycystic ovarian syndrome. Twenty
      eight women received Decapeptyl Continuous Release for 70 cycles starting on day
      3 of the menstrual cycle, after exclusion of any ovarian pathology by
      transvaginal ultrasonography. Fifteen days later ultrasonography was again
      performed and serum estradiol estimated. Cystic structures > or = 20 mm in the
      ovaries were defined as follicle cysts. In three cycles follicle cysts developed
      and low estradiol levels were measured (Group 1). In another six cycles cysts
      developed after GnRH analog, and elevated estradiol levels were found (Group 2).
      In the latter, estradiol decreased 3 to 7 days later, with cyst regression in
      three cases. Ovulation induction with human menopausal gonadotropin (hMG) was
      initiated only if the estradiol level was < or = 20 pg/ml, otherwise induction
      was postponed until estradiol decreased, disregarding the presence of cysts. When
      2 to 3 follicles were > or = 18 mm, and generally when estradiol levels were <
      1500 pg/ml, human chorionic gonadotropin was administered. All the cycles were
      ovulatory and two women from Group 2 conceived. The development of follicle cysts
      with low serum estradiol levels after GnRH analog administration represents a
      benign condition and is not a contraindication for hMG stimulation. In cases with
      elevated estradiol levels, ovulation induction can be postponed until the
      estradiol has decreased. Our study revealed good ovulatory and pregnancy rates as
      a result.

PMID- 9174851
TI  - Color Doppler analysis in oligo- and amenorrheic women with polycystic ovary
      syndrome.
AB  - The objective of this study was to determine whether amenorrheic women have more
      severe blood flow variations and clinical-endocrinological patterns in comparison
      with oligomenorrheic polycystic ovary syndrome (PCOS) patients. Twenty
      oligomenorrheic women (cycle length > 35 days; Group I), and 20 amenorrheic women
      (no vaginal bleeding for at least 6 months; Group II) were submitted to
      ultrasonographic evaluation of ovarian volume, follicle distribution, number and
      diameter, color Doppler analysis of uterine and intraovarian blood flow, hormonal
      assay of different compartments, and plasma evaluation of lipid profile. The
      number of subcapsular small-sized follicles, and the ovarian volume,
      androstenedione and luteinizing hormone (LH) plasma levels, and the LH/follicle
      stimulating hormone (FSH) ratio were significantly higher in the amenorrheic
      group compared with the oligomenorrheic patients. Furthermore, significantly
      lower high-density lipoprotein (HDL) and HDL/total cholesterol ratio were
      observed in Group II compared with Group I. In addition, in Group II, higher
      resistance in the uterine arteries and lower impedance to blood flow in the
      intraovarian arteries have been shown. The assessment of ovarian morphology by
      transvaginal ultrasound and Doppler flow analysis of both intraovarian and
      uterine arteries in patients with PCOS may provide an insight into the
      pathological state and the degree of progression of the disease.

PMID- 9174852
TI  - A twin study of polycystic ovary syndrome and lipids.
AB  - Our objective was to assess the relative contribution of genetic and
      environmental factors (particularly androgens) on circulating levels of lipid
      fractions and to determine the effect, if any, of polycystic ovary syndrome
      (PCOS) on lipid fractions. The study was carried out in the outpatient clinic of
      the Royal Hospital for Women, Paddington, Sydney, Australia. A group of 19
      monozygotic (MZ) and 15 dizygotic (DZ) twin pairs was identified from the
      National Twin Register. Ultrasound clinical and biochemical parameters were used
      to define polycystic ovaries. Serum androgen and lipid fractions were also
      measured. Eleven pairs of twins (five MZ, six DZ) were scan discordant (i.e. one
      twin had polycystic ovaries and the co-twin did not). Serum levels of the
      lipoprotein fractions in twins with polycystic ovaries were not significantly
      different from the levels found for their co-twins with normal ovaries. There
      were no significant correlations between androgen-related hormones and any of the
      lipid measurements. Body mass index (BMI) was positively correlated with
      triglycerides and lipoprotein (a), and negatively correlated with high-density
      lipoprotein cholesterol (HDL-C). Sex hormone-binding globulin (SHBG) levels were
      negatively correlated with triglycerides and lipoprotein (a) and positively
      associated with HDL-C. Fasting insulin levels were significantly correlated with
      triglycerides and negatively with HDL-C. The MZ intraclass correlation exceeded
      that of the DZ twin pairs for all the lipid variables measured. The heritability
      estimates for lipoprotein (a), apolipoprotein B, total cholesterol and HDL-C were
      0.95, 0.56, 0.48 and 0.54, respectively. However, the intraclass correlation
      coefficient for triglycerides was not significantly different between MZ and DZ
      twins, but maximum likelihood analysis indicated that at least 10% of the
      variance of the circulating triglyceride concentration is determined by genetic
      factors. We conclude that twins discordant for the PCOS do not have significantly
      different lipid fractions.

PMID- 9174853
TI  - Cyclic and individualized administration of gonadotropin-releasing hormone
      agonists plus progestogens: an alternative protocol for contraception.
AB  - Twenty-one women presenting with different diseases, with absolute or relative
      contraindications to hormonal contraception or the use of intrauterine devices,
      received 300-600 micrograms/day buserelin intranasally from the 1st to the 21st
      day, and 5 mg/day norethisterone acetate orally from the 16th to the 23rd day of
      the cycle for a total of 245 cycles. Serum luteinizing hormone (LH), follicle
      stimulating hormone (FSH), estradiol and testosterone were determined on days 3-5
      and 13-15 of the cycle, while progesterone determinations and ovarian sonography
      were performed during the second half of the cycle. According to progesterone
      values, 92.7% of the treatment cycles were anovulatory, while in one cycle
      pregnancy was detected (0.4%). Values of serum LH, FSH and estradiol were low,
      and in most of the cycles ovarian follicular development was limited to follicles
      < or = 11 mm. In 21 treatment cycles (9%), statistically significant increases in
      FSH (p < 0.0001) and LH (p < 0.02), as well as ovarian proliferation to
      preovulatory follicles or luteinized follicles, were found. It appears that in
      spite of the high cost of medication and monitoring of patients, this regimen
      could be useful as an alternative in cases where other forms of contraception are
      contraindicated or have failed.

PMID- 9174854
TI  - Effects of age and non-hormonal contraception on menstrual cycle characteristics.
AB  - The objective of this study was to investigate the effects of age and non
      hormonal contraceptive method on menstrual cycle parameters. The menstrual cycle
      data were collected prospectively, and the study was cross-sectional with regard
      to age. The subjects were 142 women, including 14 asymptomatic volunteers and 128
      women who presented to a premenstrual tension (PMT) clinic. The age range was 20
      45 years. Contraceptive methods used were intrauterine device (IUD) (n = 12),
      tubal ligation (n = 61) and non-intensive methods (n = 69). Daily menstrual cycle
      diaries were used to calculate cycle length and number of days of menstruation.
      Daily 24-h urine collections were used to calculate the day of the preovulatory
      estrogen peak. Pearson correlations found significant relationships between age
      and preovulatory estrogen peak day (p < 0.001) and length of cycle (p < 0.002),
      but not between age and length of menstruation or luteal phase. Analysis of
      variance was highly significant for age and contraceptive method, for both cycle
      length and preovulatory estrogen peak day. Non-intrusive contraception users aged
      30 years and younger had significantly longer follicular phases than did women
      with tubal ligation (p < 0.05). It was concluded that cycle length decreases with
      age due to shortening of the follicular phase. Further research on whether tubal
      ligation affects ovulation and follicular phase length in young women is needed.

PMID- 9174855
TI  - Bilateral non-communicating paraurethral meatus in Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a complex multisystemic congenital disorder due to
      an interstitial deletion of chromosome 15q11-13 or to maternal uniparental
      disomy. Molecular genetic testing is complex, and often requires DNA from both
      parents, which is not always available. An accurate medical history and
      presenting clinical signs are frequently the only tools for the clinical
      diagnosis of this syndrome, therefore it is important to have complete and
      accurate criteria. The presence of a bilateral non-communicating paraurethral
      meatus in a 9-year-old female patient affected by PWS, previously unreported in
      the literature, should induce clinicians to look for this sign when examining
      such patients.

PMID- 9174856
TI  - Control of gonadotropin feedback: the possible role of estrogen-induced
      hypothalamic synaptic plasticity.
AB  - The preovulatory gonadotropin surge is a critical event in reproduction. Although
      many explanations have been given for the inhibition--disinhibition cycle
      referred to as positive feedback, none are completely satisfactory. Recent
      evidence indicates that the preovulatory surge of gonadotropin is induced, in
      part, by the disengagement of inhibitory synaptic connections in the hypothalamic
      arcuate nucleus. This disinhibition of gonadotropin-releasing hormone secretion
      results in a massive release by the estrogen-sensitized pituitary gonadotrophs.
      Investigations are presently under way to determine whether other areas of the
      hypothalamus are involved in this estrogen-induced synaptic plasticity.

PMID- 9174857
TI  - Immune dysfunction in patients with obstructive jaundice, mediators and
      implications for treatments.
AB  - Patients with obstructive jaundice have an increased perioperative complication
      rate. Sepsis, bleeding, wound problems, renal and liver malfunction are all seen
      in these patients. Assessment of immune function has been an active research area
      in these patients. This review will examine various aspects of immune functions
      in obstructive jaundice, discuss the recent research results and controversies
      and then go on to discuss the relevant mediators of immune function and some
      possible implications for treatment.

PMID- 9174858
TI  - The internal biliary fistula--reappraisal of incidence, type, diagnosis and
      management of 33 consecutive cases.
AB  - To reevaluate the current features of spontaneous internal biliary fistulas, we
      reviewed 1,929 consecutive patients who had been treated for biliary tract
      diseases during the recent 12-year period. Thirty-three patients had internal
      biliary fistulas and the incidence was 1.9%. Of 33 patients, 20 were women and 13
      were men with the average age 63 years, and their mean duration of illness was 4
      years. A total of 37 fistulas were found and the most common type was
      choledochoduodenal (62%), followed by cholecystoduodenal (19%),
      cholecystocholedochal (11%) and cholecystocolonic (8%) fistulas. Internal biliary
      fistulas of thirty-one patients were caused by biliary stones and those of two
      patients by malignant tumors. All of the 17 bile samples examined were bacteria
      positive and the majority of calculi were brown pigment stones. All of the
      choledochoduodenal fistulas were correctly diagnosed by endoscopic retrograde
      cholangiography. In 14 patients with cholecystoenteric or cholecystocholedochal
      fistulas, direct evidence of the internal fistula was obtained only in 7 patients
      (50%) preoperatively. Pneumobilia, a small atrophic gallbladder adherent to the
      neighboring organs and a history of spontaneous disappearance of jaundice in
      elderly patients may indicate the presence of a cholecystoentric fistula. Since
      the preoperative diagnostic rate for internal biliary fistula involving the
      gallbladder is still low, care is necessary before and at the time of surgery
      especially during laparoscopic cholecystectomy for elderly patients with
      cholelithiasis.

PMID- 9174859
TI  - Microvascular architecture of hepatic metastases in a mouse model.
AB  - Development of effective treatment for hepatic metastases can be initiated by a
      better understanding of tumour vasculature and blood supply. This study was
      designed to characterise the microvascular architecture of hepatic metastases and
      observe the source of contributory blood supply from the host. Metastases were
      induced in mice by an intrasplenic injection of colon carcinoma cells (10(6)
      cells/ml.) Vascularization of tumours was studied over a three week period by
      scanning electron microscopy of microvascular corrosion casts. Metastatic liver
      involvement was observed initially within a week post induction, as areas
      approximately 100 microns in diameter not perfused by the casting resin. On
      histology these spaces corresponded to tumour cell aggregates. The following
      weeks highlighted the angiogenesis phase of these tumours as they received a
      vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of
      metastases was maintained throughout tumour growth. At the tumour periphery most
      sinusoids were compressed to form a sheath demarcating the tumour from the
      hepatic vasculature. No direct supply from the hepatic artery or the portal vein
      was observed. Dilated vessels termed vascular lakes dominated the complex
      microvascular architecture of the tumours, most tapering as they traversed
      towards the periphery. Four vascular branching patterns could be identified as
      true loops, bifurcations and trifurcations, spirals and capillary networks. The
      most significant observation in this study was the direct sinusoidal supply of
      metastases, together with the vascular lakes and the peripheral sinusoidal
      sheaths of the tumour microculature.

PMID- 9174860
TI  - Treatment of a giant haemangioma of the liver with Kasabach-Merritt syndrome by
      orthotopic liver transplant a case report.
AB  - We describe a case of giant cavernous haemangioma of the liver with disseminated
      intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by
      orthotopic liver transplant. A 47 year old man presented with bleeding and tender
      massive hepatomegaly after tooth extraction. Investigations showed disseminated
      intravascular coagulopathy and a giant hepatic haemangioma involving both lobes
      of the liver. Initial treatment failed to resolve the coagulopathy and liver
      resection was attempted. At laparotomy the tumour was unresectable and the only
      option for cure was to offer a liver transplantation. The orthotopic liver
      transplant was performed 20 days after initial laparotomy. Subsequently, all
      coagulation parameters returned to normal and the patient remains well after 12
      months. Orthotopic liver transplant can be considered for giant hepatic
      haemangioma with Kasabach-Merritt syndrome when resection is necessary and a
      partial hepatectomy is not technically feasible.

PMID- 9174861
TI  - Abdominal wall sinus: a late complication of gallstone spillage during
      laparoscopic cholecystectomy.
AB  - Long term complications of laparoscopic cholecystectomy are uncommon. However, as
      experience with this procedure accumulates, sporadic reports of non-biliary
      complication have been published. We report a case of abdominal wall sinus
      formation secondary to gallbladder perforation and stone spillage occurring
      during laparoscopic cholecystectomy.

PMID- 9174863
TI  - Laparoscopic cholecystectomy: incidental carcinoma of the gallbladder with
      abdominal wall and axillary node metastasis.
AB  - A case report is presented of intra-mural gallbladder carcinoma discovered
      incidentally after laparoscopic cholecystectomy who subsequently developed
      abdominal wall recurrence at the epigastric exit port, and axillary lymph node
      metastases. Possible preventative steps for tumour dissemination and a management
      plan if incidental carcinoma is diagnosed is discussed. The use of a non-porous
      retrieval bag, early recognition of the carcinoma and excision of the exit wound
      are advocated.

PMID- 9174862
TI  - "Gallstone hip" and other sequelae of retained gallstones.
AB  - The fate of gallstones spilled during laparoscopic cholecystostomy has been
      thought to be relatively benign. Recent experience and a review of the recent
      literature shows that this is not always the case. We report three cases of
      complications of retained stones and analyse the literature with regard to types
      of complications, time to presentation, and recommendations for managing spilled
      gallstones. Retained gallstones have been shown to cause adhesions in the rat and
      inflammatory reactions in dogs with no evidence of absorption. The average time
      to presentation of complications arising from retained gallstones is 27.3 weeks.
      Complications include: Intraabdominal abscess formation with or without abdominal
      wall sinus tract formation, persisting abdominal wall sinus tracts from port site
      abscess, subhepatic inflammatory masses, cholelithoptysis, microabscesses and
      granuloma formation, liver abscess and "dumbell" shaped abscess with one side of
      the "dumbell" forming a subcutaneous abscess. We recommend the judicious use of
      retrieval devices during the extraction phase of the laparoscopic
      cholecystectomy, diligent removal of any spilled stones and awareness of delayed
      postoperative pain and tenderness as a harbinger of symptomatic retained
      gallstones. Documentation of intraoperative gallstone spillage, volume, type of
      gallstones, and effort to retrieve is recommended.

PMID- 9174864
TI  - Transhepatic venous angioplasty and stenting: a treatment option in bleeding from
      gastric varices secondary to pancreatic carcinoma.
AB  - We present a case of recurrent variceal bleeding due to subtotal occlusion of the
      splenoportal junction by a pancreatic carcinoma. This was effectively treated by
      transhepatic venous angioplasty and stenting.

PMID- 9174866
TI  - Stent or surgery for malignant low bile duct obstruction?

PMID- 9174865
TI  - Is there a role for perioperative nutritional support in liver resection?

PMID- 9174867
TI  - ICG clearance in assessing cirrhotic patients with hepatocellular carcinoma for
      major hepatic resection.

PMID- 9174868
TI  - Should the distal splenorenal shunt be combined with gastric disconnection and
      transection?

PMID- 9174869
TI  - The role of laparoscopy and ultrasonography in pancreatic head carcinoma.

PMID- 9174870
TI  - Operative vs non-operative management in sterile necrotizing pancreatitis.

PMID- 9174871
TI  - Jejunum or stomach for the pancreatic anastomosis after pancreaticoduodenectomy.

PMID- 9174872
TI  - Left ventricular and microvascular hypertrophy in essential hypertension:
      clinical relevance and prognostic implications.
AB  - A considerable number of patients with essential hypertension develop cardiac and
      vascular structural and functional alterations, indicating an adaptation to the
      persistently elevated blood pressure. Besides the mechanical stress, neuro
      humoral stimuli and possibly the genetic disposition contribute to the process of
      cardiovascular hypertrophy and remodeling. Left ventricular hypertrophy has been
      identified as an independent risk factor for cardiovascular events and mortality
      in these patients and therefore regression of cardiac hypertrophy seems to be a
      meaningful therapeutic goal. A normalization of myocardial hypertrophy can be
      achieved with various antihypertensive drugs and combinations, where angiotensin
      converting enzyme inhibitors seem to be the most powerful substances. This
      observation emphasizes the role of the renin-angiotensin-aldosterone system in
      cardiac diseases. Morphological changes in small resistance arteries do not only
      represent an adaptation to an elevated peripheral resistance, moreover, they
      contribute to the persistence of the increase in blood pressure. Investigations
      on the potential reversibility of small vessel alterations in humans as well as
      the association with regression of left ventricular hypertrophy will be discussed
      in this review.

PMID- 9174873
TI  - Advances in dermatopharmacology--strength and weakness of recently of approved
      drugs (I).

PMID- 9174874
TI  - Nilvadipine in hypertension--experience in ambulatory treatment.
AB  - To investigate the 24-hour efficacy of nilvadipine (8 and 16 mg)in patients with
      mild to moderate essential hypertension, a double-blind, randomized, placebo
      controlled, multicenter study with 3 parallel medication groups (placebo, 8, and
      16 mg nilvadipine) was performed. Included in the study were 172 outpatients of
      both sexes with a mean age of 56 years. The primary target variable for the
      evaluation of efficacy was the difference in sitting diastolic blood pressure 24
      hours after administration of the trial medication, in mmHg, achieved by the
      different doses after 8 weeks of therapy compared to baseline. This difference
      was -6.8 in the placebo group (n = 59), -10.4 in the nilvadipine 8 mg group (n =
      60), and -11.0 in the nilvadipine 16 mg group (n = 49). Paired comparison showed
      a significant and clinically relevant difference between placebo and both
      nilvadipine doses. There were no serious adverse events reported. Nonserious
      adverse events were reported in 40.1% of all patients. Most frequently reported
      adverse drug reactions were flushing, headache, edema, and tachycardia. The
      adverse events occurred dose-dependently. As the dose-response relationship shows
      clinical saturation at a daily dose of 16 mg, the recommended dose is 8 mg taken
      once daily.

PMID- 9174875
TI  - Renal excretion of tetracycline is transiently decreased during short-term heat
      exposure.
AB  - Renal blood flow is known to be reduced during intensive external heating, which
      may have clinical relevance for renal drug elimination as well. The effects of
      heat exposure in a sauna bath on tetracycline pharmacokinetics were studied in 8
      healthy volunteers in an open, randomized crossover study. The subjects were
      given a single oral dose of tetracycline (500 mg) both in a control session and
      in a sauna bathing session. The heat exposure consisted of three 10-minute stays
      in a sauna bath (temperature 76-87 degrees C, relative humidity 27-33%) starting
      20 minutes after drug administration. The stays in the steam room were separated
      by two 5-minute cooling periods at 23 degrees C. Venous blood samples for
      determination of plasma tetracycline concentrations were taken 15 min before the
      drug intake, 20, 40, 60 min, and 2, 3, 4, 6, 8, and 24 h after it. The control
      session at room temperature (23 degrees C) followed the same sampling protocol.
      No statistically significant differences in tetracycline plasma concentrations,
      Cmax, Tmax, or AUC0-24h were seen. In addition, urine was collected (0-2 h, 2-5
      h, 5-8 h, and 8-24 h) for determination of the amount of tetracycline excreted
      unchanged. Urinary tetracycline excretion was transiently (2-5 h after drug
      intake) reduced in the sauna session (P < 0.05 vs. control, Wilcoxon). The other
      collection periods and the total urinary excretion of tetracycline (24 h) did not
      differ from the control session. It is concluded that urinary tetracycline
      excretion was transiently decreased during short-term heat exposure, but
      otherwise the effects of external heating on tetracycline pharmacokinetics were
      negligible.

PMID- 9174876
TI  - Effect of inhaled heparin on adenosine-induced bronchial hyperreactivity.
AB  - Glycosaminoglycan heparin possesses multiple noncoagulant properties including
      antiinflammatory actions. We have previously shown that heparin attenuates the
      methacholine-induced bronchoconstriction in humans. In contrast to methacholine,
      a stimulus that induces airway constriction mainly by "direct" stimulation of
      airway smooth muscle cells, adenosine airway responsiveness reflects "indirectly"
      induced airway narrowing via inflammatory mediators or neural reflex mechanisms.
      Whether heparin modulates bronchial hyperreactivity induced by adenosine, is not
      well known. We investigated the effect of inhaled heparin on adenosine-induced
      bronchoconstriction and compared the inhibitory role of heparin on the adenosine
      challenge test with that on the methacholine challenge test. Fifteen subjects (7
      males, 8 females) with mild asthma were included in the study. Bronchial
      provocation tests were performed in a single-blind, crossover, randomized order,
      and repeated 45 minutes after placebo or aerosolized heparin inhalation (1,000
      U/kg). The heparin increased the geometric mean log methacholine PD20 value from
      0.47 +/- 0.16 (2.95 mg/ml) to 0.96 +/- 0.10 (8.91 mg/ml), (P < 0.0009) in 15
      patients and the geometric mean log adenosine PD20 values from 1.59 +/- 0.23
      (38.9 mg/ml) to 1.98 +/- 0.14 (97.7 mg/ml) (NS) in 7 patients whose baseline
      adenosine PD20 levels were less than 200 mg/ml. The degree of protection by
      heparin against adenosine-induced bronchoconstriction was not correlated with
      that against methacholine-induced bronchoconstriction (r = 0.60, NS). The data
      suggest that inhaled heparin may have an inhibitory effect on the methacholine
      bronchial challenge, and thus, most likely directs its effect against smooth
      muscle. Heparin caused less attenuation of a challenge with adenosine and
      probably does not affect mast cell degranulation.

PMID- 9174877
TI  - Comparative tear concentrations of topically applied ciprofloxacin, ofloxacin,
      and norfloxacin in human eyes.
AB  - The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3%
      norfloxacin ophthalmic solutions after a single drop topically administrations in
      the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30,
      120, 180, and 240 minutes, were analyzed for drug concentrations by high
      performance liquid chromatography (HPLC) with fluorometric detection. Topically
      applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear
      concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78
      micrograms/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79
      +/- 4.80 micrograms/g at 240 min, respectively. Topical norfloxacin achieved mean
      tear level significantly higher than ofloxacin at 30 min (p = 0.031). There were
      no statistically significant differences in the mean tear levels of ciprofloxacin
      versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin
      (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and
      240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and
      norfloxacin, fell to the statistically significant concentrations (p = 0.02 and p
      = 0.01, respectively). But, it is concluded that concentrations of ciprofloxacin,
      ofloxacin, and norfloxacin in tears were still significantly greater than the
      minimum inhibitory concentrations for the most sensitive organisms, 240 min after
      a single drop application.

PMID- 9174878
TI  - Comparative study of oral clonidine and diazepam as premedicants in children.
AB  - In a prospective, double-blind, controlled study the efficacy of clonidine was
      assessed in children, with respect to sedation, intubation response, and
      recovery. Fifty children, aged 4-12 years, undergoing general anesthesia were
      studied. Twenty-five children (group I) received oral diazepam) 0.2 mg/kg and
      another 25 children (group II) received oral clonidine 3 micrograms/kg, 90-120
      minutes before induction of anesthesia. The level of sedation, hemodynamic
      changes to laryngoscopy and intubation, the recovery from anesthesia were noted
      and compared between the groups. Clonidine 3 micrograms/kg produced sedation
      comparable to diazepam 0.2 mg/kg (p > 0.1). There was significant (p > 0.01)
      attenuation of hemodynamic intubation response with clonidine. The recovery with
      clonidine was not delayed (p < 0.01). Clinically significant hypotension and
      bradycardia were not observed in any of the patients. We conclude that clonidine
      3 micrograms/kg produces sedation comparable to diazepam 0.2 mg/kg and also
      attenuates the intubation response without increasing the incidence of
      complications.

PMID- 9174879
TI  - [Reproducibility of spasm in patients with long-term remission of vasospastic
      angina by medical treatment].
AB  - The reproducibility of coronary vasospasm was assessed in nine patients with
      complete remission of vasospastic angina by medical treatment by reexamination at
      intervals of mean [+/-SD] 5.7 +/- 0.9 years. Twenty-one segments were defined as
      spastic, demonstrating more than 90% narrowing after acetylcholine injection at
      the initial angiography. The degree of spasticity, type of spasm (diffuse or
      focal) and coronary artery diameter in these segments at the initial and follow
      up studies were compared. Of the 21 segments, 17 (81%) still had some spasticity
      (> 25%) at the follow-up study and 8 (38%) of these 17 showed spasticity with
      greater than 90% narrowing. On the other hand, spasm was not reprovoked in 4
      (19%) segments. Luminal diameter of the spastic segments decreased significantly
      at the follow-up study (2.52 +/- 0.83 vs 2.26 +/- 0.62 mm, p = 0.01), but
      percentage stenosis was not different between the initial and follow-up studies
      (9.1 +/- 7.2 vs 10.3 +/- 8.0%, NS). The reproducibility of the type of spasm
      provoked was 83%. Coronary vasospasticity persists to some extent in spite of
      complete remission of angina by medical treatment, and the type of spasm provoked
      has high reproducibility. Therefore, the cessation of drug treatment should be
      done carefully.

PMID- 9174880
TI  - [Percutaneous transluminal coronary angioplasty in patients with multivessel
      coronary disease: does complete revascularization improve the long-term
      survival?].
AB  - The influence of complete revascularization on long-term outcome of patients with
      multivessel coronary artery disease undergoing percutaneous transluminal coronary
      angioplasty (PTCA) was determined by analysis of 10-year survival in 167
      consecutive patients treated at Juntendo University Hospital during 1984-1993.
      Forty-nine patients were completely revascularized and 118 had incomplete
      revascularization according to the anatomical classification. Among patients with
      anatomically incomplete revascularization, 56 were categorized as functionally
      adequate revascularization and 62 as functionally inadequate revascularization
      according to Faxon's criteria. Baseline characteristics showed incompletely
      revascularized patients had a higher incidence of prior myocardial infarction
      triple-vessel disease and/or chronic total occlusion in at least one lesion. The
      10-year survival was slightly better in patients with complete (100%) than in
      those with incomplete revascularization (79%), but not statistically significant
      (p = 0.089). Event-free survival was not significantly different between the two
      groups. However, the need for coronary artery bypass surgery was higher in the
      incomplete revascularization group than that in the complete revascularization
      group (100% vs 81%, p = 0.013). The influence of the degree of functional
      revascularization on outcome was not clear in the present study. Long-term
      survival appeared to be better in patients with complete revascularization than
      that in patients with incomplete revascularization, but even in the latter,
      coronary artery bypass grafting in the later period could improve outcome. The
      effect of functional revascularization status should be further investigated in a
      larger population.

PMID- 9174881
TI  - [Risk of side branch occlusion after coronary Palmaz-Schatz stenting].
AB  - The immediate and long-term patency of lesion-associated side branches after
      Palmaz-Schatz stent implantation was assessed by coronary angiography in 78
      patients (83 lesions) at baseline, before and immediately after Palmaz-Schatz
      stent placement, and at 6 months. The patency of side branches was then analyzed.
      Of 83 lesions stented, 48 stent placements spanned 53 side branches with a
      diameter > or = 0.5 mm. Ten (19%) side branches were occluded before and 14 (26%)
      after stenting, and 4 (8%) at 6 months. Side branch ostial stenosis (> or = 50%)
      was present in 17 side branches; 5 (29%) with ostial stenosis became occluded
      before and 12 (71%) after stenting. Four of nine (44%) side branches arising from
      stenosis became occluded after predilatation and five (56%) after stenting. These
      findings demonstrate that both ostial stenosis and the location of side branches
      are associated with side branch occlusion.

PMID- 9174882
TI  - [Sudden death in acute pulmonary embolism].
AB  - A current problem associated with pulmonary thromboembolism is the absence of a
      decrease in the mortality rate, which seems due to overlooking of the disease and
      subsequent sudden death. This study tried to find methods to decrease the
      mortality rate through a clinical investigation of sudden death. Of 162 patients,
      44 suffered sudden death (within 24 hours of onset). Among these, 28 patients
      died within 1 hour and 9 within 1 to 24 hours. In the remaining seven patients,
      the time until death could not be determined because the subject was detected
      postmortem. Pathological examination revealed occlusion of the pulmonary trunk or
      the bilateral pulmonary arteries in 58% (23/40). All patients who did not receive
      adequate cardiopulmonary resuscitation suffered occlusion at these sites.
      Occlusion of one of the pulmonary arteries or of the peripheral arteries alone
      was found in 42% (17/40) and all these patients received adequate cardiopulmonary
      resuscitation. In addition, the incidence of cardiopulmonary disease was 56% in
      this group, which was higher than the rate of 35% for the group with central
      occlusion. Of the nine patients with sudden death after 1 to 24 hours, five died
      at 5 or more hours after the onset and none had been examined by a physician.
      Among patients dying within 1 hour, 60% of those with onset outside hospital had
      preexisting symptoms, suggesting sudden death can be avoided by educating the
      general population about the major symptoms. In contrast, the frequency of
      preexisting symptoms in the inpatients was low. As it is difficult to
      differentiate preexisting symptoms from symptoms caused by the underlying
      disease, it may be impossible to predict sudden death due to acute pulmonary
      thromboembolism. Therefore, better measures to prevent deep vein thrombosis are
      required.

PMID- 9174883
TI  - Early detection of left atrial thrombus in acute cardiogenic cerebral embolism by
      transesophageal echocardiography.
AB  - Re-embolization tends to occur during the first 14 days after the onset of
      cardiogenic cerebral embolism. The usefulness of early transesophageal
      echocardiography (TEE) was investigated in 64 patients (33 men and 31 women, mean
      [+/-SD] age 70.1 +/- 12.6 years) who underwent TEE within 30 days of the onset of
      cardiogenic cerebral embolism. Patients were retrospectively classified into two
      groups based on the time from the onset of the embolism to performance of TEE:
      group A consisted of 33 who underwent TEE within 4 days of the onset and group B
      consisted of 31 who underwent TEE 5 to 30 days after the onset. Transthoracic
      echocardiography visualized a left atrial thrombus in two patients, and TEE
      detected thrombi in 14 patients: 11 in group A and 3 in group B. Lethal re
      embolization occurred in two patients in group A who had highly mobile thrombi.
      Early TEE may be useful for detecting left atrial thrombi and predicting the risk
      of re-embolization in patients with acute cardiogenic cerebral embolism.

PMID- 9174884
TI  - Effects of Albunex infusion on left ventricular inflow velocity in dogs.
AB  - This study examined the effects of Albunex (sonicated 5% human serum albumin)
      infusion on left ventricular inflow velocity by Doppler echocardiography. Left
      ventricular pressure and left ventricular inflow velocity were recorded
      simultaneously under eight different conditions in dogs: 1) baseline 1 (control),
      2) Albunex 0.2 ml/kg, 3) baseline 2, 4) Albunex 0.5 ml/kg, infusion of dextran
      100 ml, 5) baseline 3, 6) Albunex 0.2 ml/kg, 7) baseline 4, and 8) Albunex 0.5
      ml/kg. In the normal state (no dextran), Albunex (0.2 ml/kg) caused no
      hemodynamic changes or inflow velocity changes. In contrast, infusion of Albunex
      (0.5 ml/kg) caused time velocity integrals of early filling to increase from the
      baseline (5.51 +/- 1.13 vs 7.19 +/- 1.14 cm, p < 0.05). After dextran infusion
      (100 ml), Albunex (0.2 ml/kg) caused peak early filling velocity to increase
      (62.4 +/- 6.9 vs 67.3 +/- 9.4 cm/sec, p < 0.05), and infusion of Albunex (0.5
      ml/kg) also caused peak early filling velocity to increase from baseline (64.6 +/
      8.5 vs 73.7 +/- 14.5 cm/sec, p < 0.05). Infusion of Albunex (0.5 ml/kg) after
      dextran infusion caused increases in left ventricular pressure at the mitral
      valve opening (12.7 +/- 3.1 vs 15.2 +/- 3.3 mmHg, p < 0.05) and in left atrial
      driving force (13.5 +/- 3.6 vs 16.7 +/- 5.9 mmHg, p < 0.05). Clinicians should be
      cautious about using Albunex at doses of greater than 0.2 ml/kg when evaluating
      the pressure gradient of the left ventricle in patients with elevated left
      ventricular diastolic pressure. In patients with normal hemodynamics, Albunex
      infusion at doses of less than 0.2 ml/kg apparently did not affect the velocity
      measurement.

PMID- 9174885
TI  - [An isolated premature ventricular contraction can predict the clinical course of
      a 55-year-old man with acute myocardial infarction].

PMID- 9174886
TI  - Reconstruction of extensive defects of the parotid region: experience with the
      pectoralis major and free latissimus dorsi flaps.
AB  - Large defects of the parotid region resulting from excision of malignant tumours,
      or necrotic tissue due to radiotherapy, should not always be closed with local
      tissue, for several reasons. Occasionally, myocutaneous flaps are indicated,
      giving better results. We describe the problems of such tissue defects and our
      experience over a 10-year period using 2 different flap reconstruction
      techniques. A total of 28 cases, 25 with malignant tumours of the parotid or the
      external ear, 2 with extensive radionecrosis of the parotid region and 1 with a
      burn, were evaluated. The defects were restored with a pectoralis major flap in
      21 cases and with a free latissimus dorsi flap in 7 cases. The follow-up ranged
      from 18 to 60 months. The flaps were successful in achieving stable wound
      healing, restoration of tissue volume and in helping patients to return to normal
      life activities. There were complications in 28.5% of the cases. There were 2
      early deaths due to encephalitis. Two pectoralis major flaps (9.5%) failed
      partially. All latissimus dorsi flaps survived. The pectoralis major proved to be
      useful, especially in older and medically compromised patients, whereas the
      latissimus dorsi fared well in younger female patients and in cases of a
      hemifacial resection defect. Numerous technical points in both methods are
      emphasized.

PMID- 9174887
TI  - Use of Bioplant HTR synthetic bone to eliminate major jawbone defects: long-term
      human histological examinations.
AB  - This article describes the long-term follow-up of Bioplant HTR Synthetic bone
      (HTR: hard tissue replacement) in the human organism, as revealed by clinical,
      radiological and histological examinations and observations over a period of 5
      years. Twenty-nine patients with lesions, 9 keratocysts, 16 radicular cysts, 3
      traumatic cysts and 1 odontome were followed continuously during this period. All
      patients selected for follow-up had two criteria in common: the initial
      intervention had been performed at least 5 years previously; and the largest
      diameter of the bone defect was at least 2 cm. In all cases, when large bone
      defects were filled with HTR, the cavity was eventually filled with newly formed
      and remodelled bone. The process of ossification was relatively slow. In these
      cases, complete bony regeneration took up to 5 years. Ossification did not
      continue in the soft parts around the bone cavity. The histological pictures
      confirmed complete bone healing over the time.

PMID- 9174888
TI  - Fibroblast growth factors, their receptors and receptor disorders.

PMID- 9174889
TI  - Surgical maxillary expansion: a new minimally invasive technique.
AB  - This paper describes the author's surgical maxillary expansion technique using a
      2 mm osteotome. The use of this osteotome avoids the classical mucoperiosteal
      incision, thus a less traumatic and invasive procedure is performed. From 1992 to
      1995, 24 surgical osteotomy cases were performed using this minimally invasive
      technique. Successful maxillary expansion was obtained in 23 cases. If the
      minimally invasive technique is unsuccessful, it can be converted into a
      traditional technique procedure during surgery, thus neither an anatomical nor a
      technical compromise will be required. Both the past and present literature
      concerning various theories as to which suture line is primarily involved in
      producing resistance against maxillary expansion is reviewed. From his personal
      experience, the author has seen that the maxillary midline suture does not play a
      primary role in permitting maxillary expansion but instead he found the zygomatic
      maxillary and pterygoid-palatine sutures to be of primary importance.

PMID- 9174890
TI  - The optimal vestibuloplasty in preprosthetic surgery of the mandible.
AB  - Two studies (1981-1990 retrospective, and 1989-1993 prospective) were performed
      to determine the optimal methods in preprosthetic surgery. The first study deals
      with four different types of grafts (split-thickness skin, mucosal, mesh mucosal,
      palatal) in combination with vestibuloplasties and lowering of the floor of the
      mouth. The parameters, vestibular depth, mobility and resilience of the
      transplants were examined. Keratinized grafts (split-thickness skin and palatal)
      showed advantages. On the basis of a high rate of complications at the site of
      harvesting of palatal mucosa and the limited amount of palatal mucosa available
      for grafting, we prefer a split-thickness skin graft. A second prospective study
      to compare the Edlan- and Kazanjian-plasty showed the disadvantages of both
      methods. The Edlan-plasty, in combination with implants, showed a small amount of
      bone resorption; the Kazanjian-plasty showed a significant loss of attached
      mucosa. Both methods were therefore abandoned in our clinic. For cases with
      insufficient width of attached mucosa, we recommend a vestibuloplasty
      secondarily, with keratinized grafts. If there is a deep palatal vault and the
      need for a large amount of graft material, a split-thickness skin graft should be
      harvested. In cases of limited need and flat palatal vault, the graft can be
      harvested from the palate.

PMID- 9174891
TI  - Surgical management of mandibular malposition after malunited condylar fractures
      in adults.
AB  - Fourteen patients who had occlusal disturbance and mandibular malposition
      following malunited condylar fractures are presented, to demonstrate the variety
      of surgical corrective procedures used. In order to achieve an anatomically
      correct mandibular position, a subcondylar osteotomy was performed in 2 patients,
      and in 11 patients a uni- or bilateral sagittal split osteotomy was carried out.
      In 1 patient, a Le Fort I osteotomy was the method of choice. In all patients, it
      was possible to correct the occlusal and mandibular imbalance, as well as to
      facilitate normal mandibular movement.

PMID- 9174892
TI  - The assessment of trigeminal sensory nerve paraesthesia after bilateral sagittal
      split osteotomy: modified somatosensory evoked potentials recording method.
AB  - Trigeminal neurosensory impairment is frequently observed following orthognathic
      surgery. The purpose of the present study is to visualize the degree of
      trigeminal nerve impairment following bilateral sagittal split osteotomy (BSSO).
      Twenty patients who underwent BSSO were in the present study. To record the
      modified somatosensory evoked potentials (SEP), two electrostimulation clips were
      applied. One clip was placed on the mucous surface of the lower lip and the other
      was placed on the skin surface. Each contact surface contained a separate 2 mm
      diameter silver anode and cathode attached to a 5 x 15 mm basement plate. The
      results obtained using this method revealed that complete recovery from neural
      impairment was observed in 7 cases (36.8%) on the right operative side and 4
      (20.0%) on the left side at 6 months postoperatively. A definite delay in latency
      was observed on the left operative side at all the examination periods. The
      recovery period evaluated by the SEP method was longer than that of the objective
      two-point discrimination thresholds. Clinical records obtained showed
      considerable implications for trigeminal nerve function after BSSO.

PMID- 9174893
TI  - Glenotemporal osteotomy as a definitive treatment for recurrent dislocation of
      the jaw.

PMID- 9174894
TI  - Estimation of the cut-off value in cardiovascular autonomic nervous function
      tests: not-age-related criteria or the age-related 5th percentile.
AB  - The aim of the study was to estimate the cut-off value of cardiovascular tests
      using not-age-related criteria or the age-related 5th percentile in 165 diabetic
      patients. The cANP, pANP, and smNP were assessed using previously recommended
      standardized test procedures. Prevalence of overall definite (borderline) cANP
      was 35.2% (23.0%) when using the 5th percentile or 16.4% (27.9%) when using not
      age-related criteria (p for the difference < 0.0001) (p = 0.3205). Prevalence of
      pANP was 54.0% and of smNP 37.0%. Concerning cANP, the number of test results
      below the 5th percentile (N5) correlated significantly with the number of
      abnormal test results using not age-related criteria (Nnar) (p < 0.000001) but
      the slope of the regression line differed substantially from 1. Using the 5th
      percentile as the cut-off value for cANP testing, sensitivity and specificity
      were calculated for not age-related criteria for respiratory sinus arrhythmia
      (90.5%, 80.2%), Valsalva test (30.4%, 98.0%), lying-to-standing test (46.3%,
      98.7%), orthostatic systolic blood pressure fall (69.0%, 78.3%), and overall
      definite cANP (44.8%, 92.8%). The statistical analysis revealed that the age
      related 5th percentile is superior to the not-age-related cut-off values in
      diabetic patients. We therefore suggest that age-related normal values
      (percentiles) have to be applied when cANP is estimated.

PMID- 9174895
TI  - Glycemic control in patients with type I diabetes and normoalbuminuria after long
      diabetes duration.
AB  - The importance of glycemic control for the avoidance of micro- and
      macroalbuminuria after a diabetes duration of 20 years or more was studied in
      type I (insulin-dependent) diabetic patients diagnosed before an age of 31 years.
      Glycemic control was assessed as glycated hemoglobin for 5 years or more, on
      average 9.8 years with 3.2 measurements per year. Of the 197 included patients,
      97 men and 100 women, 112 were normoalbuminuric, 45 had microalbuminuria (20-200
      mg/L), and 40 had macroalbuminuria (persistent albuminuria > 200 mg/L).
      Normoalbuminuric patients had a mean HbA1c +/- SEM for the whole measurement
      period of 6.9 +/- 0.08%, the microalbuminuric patients 7.3 +/- 0.14% (Mann
      Whitney test versus normoalbuminuric group, p = 0.025), and macroalbuminuric
      patients 7.6 +/- 0.13 (p < 0.001). The patients were on average 45 years old, and
      had an age at onset of 14 years, without significant differences between the
      groups. Thirteen patients had regressed from macroalbuminuria to normo- (n = 6)
      or microalbuminuria (n = 7). Of the normoalbuminuric patients, 43% were male,
      compared to 44% with microalbuminuria and 73% with macroalbuminuria (chi 2, p =
      0.026). Logistic regression, with absence of albuminuria as dependent variable,
      showed a beneficial impact from lower HbA1c and normal blood pressure (blood
      pressure < 140/90 mm Hg without antihypertensive treatment). In conclusion, these
      results suggests that absence of albuminuria after 20 years or more of diabetes
      is associated with lower HbA1c.

PMID- 9174896
TI  - Altered endothelial/pericyte ratio in Goto-Kakizaki rat retina.
AB  - The Goto-Kakizaki (GK) rat represents a model of hereditary non-insulin-dependent
      diabetes mellitus (NIDDM), characterized by nonobesity, mild hyperglycemia from
      early life, impaired glucose tolerance test results, and a markedly defective
      insulin response to glucose. The rats develop signs of both nephropathy and
      neuropathy, but, to our knowledge, retinal changes have not been reported so far
      in this model of NIDDM. Hence, the aim of the present study was to assess whether
      morphological vascular changes could be demonstrated in retinal vessel
      preparations of GK rats. The endothelial/pericyte ratio was found to be higher in
      GK rats aged 8 months as well as after 24-30 months compared to their matched
      controls (2.3 +/- 0.2 versus 2.0 +/- 0.1; p < 0.01, and 2.6 +/- 0.2 versus 1.9 +/
      0.1; p < 0.001, respectively). Furthermore, in 24 to 30-months-old GK rats, the
      endothelial/pericyte ratio was higher than in 8 month old GK rats (p < 0.05).
      Thus, the GK rat appears to be a suitable model for experimental studies of
      chronic complications, including diabetic retinopathy, in NIDDM.

PMID- 9174897
TI  - Characteristics, clinical course, and in-hospital mortality of non-insulin
      dependent diabetic and nondiabetic patients with acute myocardial infarction in
      Argentina.
AB  - The characteristics and clinical course of 1040 cases of acute myocardial
      infarction (AMI) among non-insulin-dependent diabetics (146) and nondiabetics
      (894) were compared. Patients with non-insulin-dependent diabetes mellitus
      (NIDDM) historically showed a greater percentage of AMI, angina, and risk factors
      than nondiabetic patients. Although the degree of left-ventricular function upon
      admission (according to the Killip and Kimball scores) was similar in both the
      diabetic and nondiabetic groups, the prevalence of hypertension and
      hypercholesterolemia was significantly higher in the NIDDM patients. All told,
      NIDDM cases were 1.73 [relative risk (RR)] times more likely to die of AMI than
      nondiabetic patients. The age factor and the presence of shock of any type also
      significantly increased the case-fatality rate. Diabetic patients showed signs of
      successful reperfusion less often than control subjects, an event that was
      closely associated with their case-fatality rate. In the NIDDM group, both the
      age and gender factor as well as a history of either casual or in-hospital
      clinical events such as cardiogenic shock, reinfarction, unsuccessful
      reperfusion, and incidence of anterior AMI along with either pain or previous
      angina were clear prognosticators of poor outcome from AMI. In the nondiabetic
      group, cardiogenic shock and hypertension were indicators of poor prognosis.
      These results would suggest that an improvement in the incidence of successful
      reperfusion in NIDDM patients, particularly in the face of clinical indicators of
      poor AMI prognosis, could decrease the high AMI mortality currently observed in
      these patients.

PMID- 9174898
TI  - Evaluation of diabetic retinopathy during pregnancy by green monochromatic fundus
      photography.

PMID- 9174899
TI  - High glucose and hyperosmolarity increase secretion of interleukin-1 beta in
      cultured human aortic endothelial cells.
AB  - Interleukin-1 (IL-1) is secreted by endothelial cells (ECs) and smooth-muscle
      cells (SMCs), which are two major component cells of vessels and detected in
      atherosclerotic lesions. To evaluate the effect of hyperglycemia on the secretion
      of IL-1 beta in endothelial cells in diabetic patients, we investigated the
      effects of high glucose and hyperosmolar conditions on the secretion of IL-1 beta
      from cultured human aortic endothelial cells (HAECs). HAECs were treated with
      high concentration of glucose or hyperosmolar condition for 3 days. IL-1 beta in
      the supernatant was measured by high sensitive enzyme-linked immunosorbent assay
      (ELISA). Under high concentration of glucose (16.6 mmol/L) and hyperosmolar
      condition (glucose 5.5 mmol/L + mannitol 11.1 mmol/L), the secretion of IL-1 beta
      was significantly increased (41.0 +/- 2.8 and 26.3 +/- 5.9% increase,
      respectively, compared with that of 5.5 mmol/L glucose). In conclusion, high
      glucose and hyperosmolar condition increase the secretion of IL-1 beta in HAECs.
      The results suggest that diabetic macroangiopathies might be accelerated partly
      through the increase of IL-1 beta secretion in HAECs.

PMID- 9174900
TI  - Factors involved in cardiac autonomic neuropathy in diabetic patients.
AB  - The role cardiac autonomic neuropathy (CAN) plays in diabetes is not well known.
      The aim of this study was to identify the factors involved in CAN in diabetic
      patients. One hundred patients, 44 insulin-dependent (IDDM) and 56 non-insulin
      dependent (NIDDM), were investigated, using five standard tests. Three of these
      tests were for parasympathetic control (cardiac response to the lying-to
      standing, deep breathing, and Valsalva tests), and the other two measured
      sympathetic control (testing for orthostatic hypotension and evaluating heart and
      blood pressure response to the handgrip test). Results were compared to those
      found in a series of 40 healthy volunteers. An age-adjusted comparison with the
      controls, showed that 34 patients had one abnormal parasympathetic test, 23 had
      two, and 6 patients had three. Cardiac parasympathetic neuropathy was thus
      present in 63% of the patients. The handgrip test was completed by 84 diabetic
      patients. There was evidence of orthostatic hypotension and/or an abnormal
      cardiac response to the handgrip in 15 of these patients, who all had a
      parasympathetic abnormality as well. There was no significant association between
      the type of diabetes and the presence of CAN. The duration of diabetes was
      significantly longer in patients with CAN (9.3 +/- 0.9 years) (p < 0.01) than in
      those with all three parasympathetic tests normal (5.8 +/- 0.9 years) (p < 0.01).
      The HbA1c level was also higher in patients with CAN than in those with three
      normal parasympathetic tests (9.95 +/- 0.35% versus 8.17 +/- 0.42%, p < 0.005).
      There was a significant association between the presence of retinopathy, observed
      by angiofluorography, and the presence of peripheral neuropathy confirmed by the
      electrophysiological investigation and the presence of CAN (p < 0.001). However,
      more than half the patients without retinopathy or nephropathy had CAN, and 11 of
      the 31 patients with a normal electrophysiological investigation also had CAN.
      Eighteen patients (6 IDDM) without retinopathy and nephropathy, who had been
      diabetic for less than 2 years, also had CAN. This study shows that CAN occurs
      early and is frequently found in a population of unselected diabetic patients.
      Metabolic factors may play an important role in its occurrence. CAN is
      significantly associated with the presence of retinopathy, which suggests that an
      impairment of autonomic peripheral blood flow control might be a contributing
      factor in the formation of microvascular lesions.

PMID- 9174901
TI  - Relationships among glomerular filtration rate, albuminuria, and autonomic nerve
      function in insulin-dependent and non-insulin-dependent diabetes mellitus.
AB  - The associations among autonomic neuropathy, urinary albumin excretion, and
      glomerular filtration rate (GFR) measured with 51Cr-EDTA and iohexol clearance
      were studied in 41 patients with insulin-dependent diabetes mellitus (IDDM) and
      15 patients with non-insulin-dependent diabetes mellitus (NIDDM). The study
      showed that increased urinary albumin excretion was more common in NIDDM than in
      IDDM. In contrast with IDDM, albuminuria in NIDDM was not related to GFR.
      Autonomic neuropathy was common in IDDM as well as in NIDDM, and also in patients
      without nephropathy, but was not connected with hyperfiltration. Low brake index,
      an ortostatic autonomic index, was associated with nephropathy in NIDDM. Iohexol,
      a non-ionic contrast medium, was found to be a useful alternative to 51Cr-EDTA
      for determination of GFR. Moreover, comparison between conventional four-sample
      plasma clearance and single-sample clearance showed a close correlation.
      Accordingly, assessment of GFR using a single plasma sample provides reliable
      results even at high GFR values.

PMID- 9174902
TI  - Effects of cilostazol on the peripheral nerve function and structure in STZ
      induced diabetic rats.
AB  - We examined the effect of cilostazol (CZ), antiplatelet agent and potent
      vasoactive compound, which has an inhibitory effect on tissue phosphodiesterase,
      on peripheral nerve in streptozotocin-induced diabetic rats. Diabetic rats were
      fed for 12 weeks with a chow containing 0.01% or 0.03% CZ (w/w) and the results
      were compared with untreated diabetic rats. The 0.03% CZ treatment significantly
      improved motor nerve-conduction velocity and restored nerve Na+, K(+)-ATPase
      activity in diabetic rats without affecting body weight and glycated hemoglobin
      levels, but the effects of 0.01% CZ treatment did not reach statistical
      difference. Elevated sorbitol and reduced myo-inositol levels in diabetic nerve
      tissues were not influenced by CZ treatment. Structural analysis of the sural
      nerve demonstrated a partial but significant effect on decreased mean myelinated
      fiber area and atrophic changes of the axon in diabetic rats treated with 0.01%
      CZ. CZ treatment inhibited reduction of pericyte area of endoneurial microvessels
      in diabetic rats. Expansion of endoneurial microvessels and luminal area in
      relation to vascular area also tended to be inhibited by CZ treatment. Thus CZ
      treatment ameliorated, although not completely, functional and structural
      abnormalities in peripheral nerve of diabetic rats without effecting the polyol
      pathway. These results support the contention that vascular factors may play an
      important role in the etiology of experimental diabetic neuropathy and suggest
      that CZ may have a beneficial therapeutic effect on diabetic neuropathy.

PMID- 9174903
TI  - Screening for protein purification: is there an optimum adsorbent for every
      protein?

PMID- 9174904
TI  - Biorecognition of antibodies in vivo: potential in drug targeting.

PMID- 9174905
TI  - Principles and applications of flow injection analysis in biosensors.
AB  - In practical applications biosensors are often forced to operate under less than
      optimal conditions. Because of their construction, and the physical processes and
      chemical reactions involved in their operation, compromise conditions are
      frequently required to synchronize all events taking place. Therefore, and in
      order to implement functions such as periodic calibration, conditioning and
      possible regeneration of the biosensor, and, very importantly, to yield the
      freedom to select the optimum detection means, it is advantageous to use these
      devices in a flow-through mode, particularly by employing the flow injection (FI)
      approach. The capacity of FI, as offering itself as a complementary facility to
      augment the performance of biosensors, and in many cases as an attractive
      alternative, is demonstrated by reference to selected examples, comprising assays
      based on enzymatic procedures with optical and thermal detection procedures, and
      via description of a recently introduced technique for immunoassays, termed flow
      injection renewable surface immunoassays, which promises to entail powerful
      potentials and to yield compatible or better economy of operation than existing
      approaches.

PMID- 9174906
TI  - New formats of polymeric stationary phases for HPLC separations: molded
      macroporous disks and rods.
AB  - A molding process has been used for the preparation of separation media in
      different shapes such as rods and flat membrane-like disks. The polymerization is
      carried out using a mixture of monomers, porogenic solvent and free-radical
      initiator under conditions that afford macroporous materials with through-pores
      or channels large enough to provide the high flow characteristics required for
      applications in chromatography. In contrast to classical suspension
      polymerization, the solubility of monomers in water does not restrict their use.
      The versatility of the preparation technique is demonstrated in polymerizations
      involving both hydrophobic and hydrophilic monomers such as styrene,
      chloromethylstyrene, glycidyl methacrylate, alkyl methacrylates and acrylamide.
      Techniques have been developed that allow fine control of the porous properties
      of the polymers. These, in turn, determine the hydrodynamic properties of the
      separation devices that contain the molded media. Since all the mobile phase must
      flow through the separation medium, the mass transport within the molded media is
      accelerated considerably by convection. Therefore, the separations can be
      performed at much higher flow rates than in packed columns. This is particularly
      important for separations of large molecules such as proteins for which diffusion
      is a serious problem that significantly slows down the separation processes. The
      molded separation media have been used for the separation of biological compounds
      using gentle chromatographic modes such as hydrophobic interaction, ion-exchange
      and affinity chromatography during which the biological activity of the separated
      compounds is completely retained.

PMID- 9174907
TI  - Affinity liposomes in vivo: factors influencing target accumulation.
AB  - To make universal and efficient liposome-based drug carriers, liposomes should be
      able to recognize and bind other targets beyond their natural targets, the cells
      of the reticuloendothial system. To make liposomes targeted, numerous methods to
      couple active substances, primarily, monoclonal antibodies, to the liposome
      surface have been developed. Resulting immunoliposomes (or affinity liposomes)
      demonstrate good targeting to cells and organs both in vitro and in vivo.
      However, the short circulation time of immunoliposomes prevented them from
      accumulating in targets with diminished blood flow or low antigen concentration.
      Long-circulating liposomes were prepared by coupling soluble and flexible
      polymers, such as polyethylene glycol, to the liposome surface. The mechanism of
      liposome steric protection with flexible polymers is based on the formation of
      dense "conformational cloud' by a grafted polymer over the liposome surface, and
      might be analyzed in terms of a statistical model of polymer solutions. By co
      immobilization of specific antibodies and protecting polymers on the liposome
      surface, liposomes can be prepared combining both targetability and prolonged
      circulation in vivo. A biological model (experimental myocardial infarction in
      rabbit) was used to estimate the relative importance of different factors
      (liposome size and coating with protective polymer and/or specific antibody) for
      effective accumulation of liposomes in the target. Statistical analysis
      demonstrated that different types of liposomes have to be used in order to reach
      maximum absolute delivery of liposomes to the target, or maximum target-to-non
      target ratio (relative delivery). Therefore, different liposomes should be used
      as carriers of diagnostic and therapeutic agents.

PMID- 9174908
TI  - Interleukin 5 interactions with soluble and cell surface forms of its receptor.

PMID- 9174909
TI  - Affinity precipitation of proteins.
AB  - Affinity precipitation is being studied as a technique to be introduced at an
      early stage of downstream processing for the selective isolation of proteins. The
      technique utilizes a heterobifunctional ligand, which, in addition to having
      affinity for the target protein(s), possesses another function for controlling
      precipitation. The latter component is comprised of a polymer which can be made
      reversibly soluble and insoluble by altering a specific parameter such as pH or
      temperature. Different polymers of natural and synthetic origin have been used
      for this purpose. The soluble form of the ligand is used for the affinity binding
      step and precipitation is induced for obtaining separation of the affinity
      complex. Some of the polymers used in this laboratory include chitosan, alginate,
      Eudragit S-100 (copolymer of methacrylic acid and methyl methacrylate) and
      polyethyleneimine. Chitosan and alginate served as natural ligands for wheat germ
      agglutinin and pectinase, respectively. The aromatic dye Cibacron Blue 3GA
      coupled to Eudragit S 100 and polyethyleneimine way used for the affinity
      precipitation of some model enzymes such as lactate dehydrogenase and alcohol
      dehydrogenase. As prior removal of cell debris, etc., is essential for affinity
      precipitation, the possibility of integration of the technique with extraction in
      aqueous two-phase systems was also demonstrated.

PMID- 9174910
TI  - Detection of pathological changes of proteins by peptide mapping after protein
      digestion by use of oriented immobilized proteinases.
AB  - Diagnostic methods for detecting gastric diseases using chymotryptic digestion of
      pepsin are discussed. Peptide maps can be prepared using reversed-phase high
      performance liquid chromatography. Batchwise chromatography by use of membranes
      with immobilized Tyr(I2) was used for the isolation of pepsin from gastric mucosa
      extract or from human blood serum. Enzymes immobilized using suitable antibodies
      or through their sugar moieties can be used for the preparation of peptide maps
      because such enzymes share good steric accessibility to their active binding
      sites and possess increased thermal stability. Biospecific adsorption of proteins
      to immunosorbents combines the simultaneous isolation of these enzymes with their
      oriented immobilization. Proteins were stabilized by hydrophilization through the
      attachment of saccharide residues containing galactose residues. These residues
      could be activated by oxidation using galactose oxidase and subsequently
      immobilized to hydrazide-containing solid supports.

PMID- 9174911
TI  - Two lectin-like receptors for alpha 1-acid glycoprotein in mouse testis.
AB  - Three glycoforms of alpha 1-acid glycoprotein (AGP) were biotinylated to examine
      their binding in mouse testis by light microscopy. The transition from one stage
      to another in the spermatogenic cycle is marked with an appearance of a receptor
      for the Concanavalin A (Con A) non-reactive glycoform AGP-A in the cytoplasm of
      spermatocytes, young spermatids and Sertoli cells. This receptor disappears in
      the late stages of the spermatids. The Con-A intermediately reactive and the Con
      A reactive glycoforms, AGP-B and AGP-C, showed weak reaction in the cytoplasm of
      spermatocytes, spermatids and Sertoli cells and, at the last stages in the
      spermatogenic cycle, a very strong reaction in the late elongated spermatids and
      the apical extensions of Sertoli cells. The interactions are lectin-like as
      confirmed by inhibition with simple sugars. In addition, the bindings were
      inhibited by steroid hormones. AGP-A was inhibited by testosterone, oestradiol
      and progesterone, while AGP-B and AGP-C were inhibited by mannose, GlcNAc,
      cortisone, aldosterone, oestradiol and progesterone. The receptors and the
      corresponding AGP glycoforms may be adhesion molecules between Sertoli cells and
      the spermatogenic cells and may have a function as a regulatory factor for
      spermatozoa development.

PMID- 9174912
TI  - Membrane microstructural templates for enzyme domain formation.
AB  - Soluble proteins can spontaneously self-organize into two-dimensional domains at
      membrane interfaces, given sufficient mobility and specificity to membrane
      localized ligands. The authors' recent results studying interfacial domain
      formation of the membrane-active enzyme, phospholipase A2, indicate that lateral
      phase separation of heterogeneous membrane mixtures creates anionic templates of
      specific morphology onto which the enzyme deposits, forming large protein
      assemblies. Selective removal of membrane components (lysolipid or fatty acid)
      produces different enzyme interfacial responses and domain morphologies. This
      leads to the conclusion that complex chemical and physical interactions laterally
      in the lipid membrane interface as well as between bound protein molecules play a
      role in organizing protein structures.

PMID- 9174914
TI  - Reversible and irreversible immobilization of enzymes on Graphite Fibrils.
AB  - Graphite Fibrils are hollow tubes (0.01 x 1-10 microns) consisting of concentric
      layers of graphite. Fibrils can be chemically modified to introduce surface
      functionalities such as carboxyl groups. Carboxylated fibrils were further
      functionalized to amino alkyl derivatives which were covalently linked to an
      enzyme, horseradish peroxidase (HRP). HRP fibrils showed substantial catalytic
      activity. Additionally, carboxyl fibrils were derivatized with specific
      inhibitors of the enzymes beta-galactosidase (beta-Gal) and alkaline phosphatase
      (AP). Enzyme inhibitor-modified fibrils were used to specifically purify both
      beta-Gal (using beta-Gal inhibitor fibrils) and AP (using AP inhibitor fibrils)
      from mixtures of these two enzymes. These studies demonstrate the feasibility of
      using Graphite Fibrils as supports in biocatalysis and biospecific affinity
      chromatography.

PMID- 9174913
TI  - Salicylaldehyde-metal-amino acid ternary complex: a new tool for immobilized
      metal affinity chromatography.
AB  - An immobilized salicylaldehyde (sal) was used to build various salicylaldehyde
      copper-amino acid (Sal-Cu-AA) complexes which are stable at a range of pH values
      (2.0-11.0). The complexes were found to bind protein molecules as IMAC resins.
      Thirteen proteins were examined for their binding to a Sal-Cu-Gly column. The
      efficacy of the Sal-Cu-AA resin for protein separation were demonstrated by two
      examples. The first was a new purification process for garlic lectins from garlic
      crude extract. It seems that in this case the Sal-Cu-AA resins were more
      selective than IDA resin. The second was immobilization of concanavalin A (Con A)
      on the resin and using the immobilized Con A for affinity chromatography of
      mannose-rich glycoprotein ovalbumin. The Con A could be later eluted with EDTA or
      imidazole and the Sal-containing polymer could be recharged again for further
      use.

PMID- 9174915
TI  - Immobilized metal-ion affinity chromatography: imidazole proton pump and
      chromatographic sequelae. I. Proton pump.
AB  - Complexation of imidazole (Im) with an iminodiacetate (IDA) metal chelate [IDA
      M(II)] ligand of chelating gel results in an acidification of the mobile phase.
      The scope of the action of this IDA-M(II)Im 'proton pump' in IMAC is determined
      by: (a) IDA-M(II) density of the gel; (b) concentration of applied Im; and (c)
      the buffering capacity of the mobile phase. Application of Im onto a metal
      chelate column in a gradient rather than in a stepwise manner, mitigates the
      proton pump's action, as it does an increase of buffer concentration in the
      mobile phase. However, only an antecedent conversion of the metal chelate gel,
      IDA-M(II), to its Im derivative, IDA-M(II) Im, can effectively circumscribe the
      action of the proton pump. The same holds true, as anticipated, when another
      chelating ligand (nitrilotriacetate) is used.

PMID- 9174916
TI  - Polyvinyl alcohol-coated perfluorocarbon supports for metal chelating affinity
      separation of a monoclonal antibody.
AB  - The preparation, characterisation and testing of stable non-porous coated
      perfluorocarbon supports functionalised with the metal chelate, iminodiacetic
      acid (IDA) is described. Polyvinyl alcohol (PVA), a neutral hydrophilic polymer
      was esterified with perfluorooctanoyl chloride and anchored to the surface of
      solid perfluorocarbon particles through multiple fluorophilic interactions. The
      PVA-coated particles were then activated by epoxidation and coupled with IDA. The
      presence of surface-attached chelates was clearly demonstrated by the binding and
      selective desorption of Zn2+ ions. Three particulate perfluorocarbons were
      selected as potential starting materials and the conditions for preparation of
      metal chelating adsorbents optimised with respect to ease of manufacture, ligand
      density and binding capacity towards a monoclonal antibody known to bind to
      commercial Zn(2+)-IDA supports. The choice of base particle strongly influenced
      the ligand densities and specific binding capacities towards the monoclonal
      antibody that could be achieved under optimal preparative conditions. Possible
      ways in which these metal chelating adsorbents may be employed to recover the
      monoclonal antibody directly from culture vessels are discussed.

PMID- 9174917
TI  - Affinity of human anti-factor VIII antibodies for functional polystyrene
      supports.
AB  - Human anti-factor VIII antibodies (anti-FVIII) neutralize Factor VIII (FVIII)
      procoagulant activity. These antibodies appear in about 5-15 per cent of severely
      affected patients with haemophilia A treated with FVIII concentrates (Mannucci,
      1993). In order to obtain non-thrombogenic materials able to interact
      specifically with anti-FVIII, amino acids residues that mimic part of the FVIII
      molecule recognized by anti-FVIII have been grafted. Several cross-linked
      polystyrenes were functionalized with sulphonate and tyrosine sulphamide groups
      or tyrosine derivatives sulphamide groups such as methyl ester tyrosine, or the
      peptides aspartic acid methyl amide tyrosine, tyrosine aspatic acid methyl amide
      or aspartic acid aspatic acid methyl amide tyrosine. The in vitro removal of anti
      FVIII from haemophilic A plasma was performed on different supports. These
      polymers exhibit strong and selective affinity for the anti-FVIII. The amount of
      adsorbed anti-FVIII varies with the composition of the polymer and a maximum is
      achieved for 15-35 per cent of amino acid sulphamide groups. The influence of
      different chemical groups on the surface of the polymeric solid supports on the
      adsorption of anti-FVIII was also studied.

PMID- 9174918
TI  - Affinity purification of biologically active and inactive forms of recombinant
      human protein C produced in porcine mammary gland.
AB  - Recombinant human protein C (rhPC) secreted in the milk of transgenic pigs was
      studied. Transgenes having different regulatory elements of the murine milk
      protein, whey acidic protein, were used with cDNA and genomic human protein C
      (hPC) DNA sequences to obtain lower and higher expressing animals. The cDNA pigs
      had a range of expression of about 0.1-0.5 g/l milk. Two different genomic hPC
      pig lines have expressed 0.3 and 1-2 g/l, respectively. The rhPC was first
      purified at yields greater than 60 per cent using a monoclonal antibody (mAb) to
      the activation site on the heavy chain of hPC. Subsequent immunopurification with
      a calcium-dependent mAb directed to the gamma-carboxyglutamic acid domain of the
      light chain of hPC was used to fractionate a population having a higher specific
      anticoagulant activity in vitro. The higher percentages of Ca(2+)-dependent
      conformers isolated from the total rhPC by immunopurification correlated well
      with higher specific activity and lower expression. A rate limitation in gamma
      carboxylation of rhPC was clearly identified for the higher expressing animals.
      Thus, transgenic animals with high expression levels of complex recombinant
      proteins produced a lower percentage of biologically active protein.

PMID- 9174919
TI  - Alginate as a displacer for protein displacement chromatography.
AB  - Alginate use in displacement chromatography as a displacer has been studied. The
      experiments showed that untreated alginate is the basis of potential displacer
      for displacement chromatography, but needs to be cleaved into smaller chains.
      Alginate treated with ultrasound, which cleaves alginate into shorter
      polysaccharide chains, gave better displacement than untreated alginate, while
      alginate subjected to limited acid hydrolysis gave the best results in
      displacement chromatography. It was found that the mixture of ovalbumin and beta
      lactoglobulin separated well, and several components of ovalbumin were also
      separated and purified when alginate hydrolysate was used as a displacer. beta
      Lactoglobulins A and B, which have the same molecular weight and differ in
      isoelectric point by only 0.1 pH units, were displaced from Q-Sepharose by
      alginate hydrolysate.

PMID- 9174920
TI  - Peptides as affinity surfaces for protein purification.
AB  - The tetrapeptide GPRP was previously shown to be an effective affinity ligand for
      fibrinogen when immobilized to Fractogel (Kuyas et al., 1990). The authors
      synthesized the GPRP peptide directly onto an aminefunctionalized POROS
      chromatographic resin to demonstrate the effectiveness of this approach for
      generating perfusive affinity media. Fibrinogen from plasma bound to an NH2-GPRP
      POROS column under 50 mM phosphate buffer, 0.15 M NaCl, pH 7 at 15 ml/min flow
      rate. The bound fibrinogen showed weak clotting activity when eluted with 20 mM
      acetate buffer, pH 4. The peptide column did not bind denatured fibrinogen. The
      dynamic binding capacity of the column by frontal analysis was 10.2 mg/ml column
      volume. The total analysis time was under 5 min. Similarly, the CAQCHTVEK peptide
      of cytochrome c with heme group covalently attached to the SH groups of the two
      cysteines is known to bind to albumins (Adams et al., 1989). A simplified peptide
      analogue, GAQGHTVEK, was synthesized directlyon POROS resin. Under 20 mM MES, pH
      6, albumin from human serum bound specifically to this peptide column and eluted
      with a salt gradient at 0.2 M NaCl, 20 mM MES (2-[N-Morpholino]ethane sulfonic
      acid), pH 6. The dynamic binding capacity of human serum albumin by frontal
      analysis was 19 mg/ml column volume. Thus, this column can purify albumin from
      human serum under non-denaturing conditions.

PMID- 9174921
TI  - Coprecipitation of proteins with matrix ligands: scaleable protein isolation.
AB  - Matrix ligands are agents for isolating proteins out of dilute crudes by
      coprecipitating proteins. The ligands have a strong anion sulfonate head which
      initiates binding to proteins having a positive net charge, ZH+ approximately 5
      20. Initial binding tightens protein conformation and starts to squeeze water
      from conformationally motile proteins. The tails are stackable hydrophobic
      organic groups, azoaromatic dyes which draw protein-ligand complexes together.
      Proteins coprecipitate as guests, in the ligand host matrix. In addition to
      stacking, ligand tails displace water because of their bulk, and lower the
      average dielectric constant near charged groups, which reinforces the
      electrostatic component of binding. Matrix ligands protect proteins, scavenge
      them from dilute crudes (0.01-0.1 per cent protein), and densify coprecipitates.
      Detergent ions in low concentrations, 10(-4)-10(-5) M also sometimes serve as
      coprecipitating agents, entangling their tails but probably not stacking.
      Divalent metal ions, Zn++, sometimes are useful auxiliary agents. Preparative
      scaleability from crudes is demonstrated starting from 100-200 g of raw peanuts
      and raw pineapple to coprecipitate a lectin and bromelain enzyme respectively in
      1-2 h with 80-90 per cent activity yields. Ligands are released from
      coprecipitates by shifting the pH and trapping the ligands with exchange resins.
      Protein conformation tightening in solution is seen by viscosity measurements.

PMID- 9174922
TI  - Human low density lipoprotein and human serum albumin adsorption onto model
      surfaces studied by total internal reflection fluorescence and scanning force
      microscopy.
AB  - The adsorption of low density lipoprotein (LDL) and human serum albumin (HSA) to
      model surfaces of different hydrophobicities has been studied using two, surface
      sensitive, real-time, in situ techniques: total internal reflection fluorescence
      (TIRF) and scanning force microscopy (SFM). The model surfaces used were: (1)
      hydrophilic negatively charged silica (TIRF) and mica (SFM) surfaces, (2)
      hydrophobic octadecyldimethylsilyl-(ODS)-modified silica (TIRF) and ODS-modified
      oxidized silicon (SFM) surfaces and (3) amphiphilic ODS-silica gradient surfaces
      (TIRF). The kinetics of fluorescein isothiocyanate-LDL adsorption onto the ODS
      silica gradient surface from FITC-LDL solution and from a solution mixture of LDL
      and HSA showed that a transport-limited process on the clean silica changed into
      an adsorption-limited process with increasing surface coverage of ODS chains. SFM
      analysis of the in situ adsorption of LDL on hydrophilic mica demonstrated a
      steady increase in surface coverage with time which was somewhat lower than
      determined by TIRF for FITC-LDL adsorption on silica. The adsorption behavior of
      a binary mixture of HSA and LDL suggested that lateral interactions between HSA
      and LDL affect the adsorption process. The diameter of LDL adsorbed on mica and
      ODS-modified silicon has been determined using SFM to be approximately 55 nm.
      Tetrameric LDL aggregates were observed on all of the surfaces in addition to
      some dimers and trimers. Imaging LDL and HSA adsorption on clean oxidized silicon
      surfaces using "contact mode' SFM techniques was hindered by probe manipulation
      of the proteins.

PMID- 9174923
TI  - Determination of binding constants of diabodies directed against prostate
      specific antigen using electrochemiluminescence-based immunoassays.
AB  - Two diabody molecules directed against the prostate-specific antigen (PSA) were
      generated from a combinatorial phage display library. The C-termini of diabodies
      incorporated the FLAG peptide epitope (P008D diabody) or the myc epitope (P001D).
      Both diabodies have the same antigen-binding site. Equilibrium-binding constants
      of these molecules were determined in two immunoassays using the ORIGEN detection
      system based on electrochemiluminescence. The binding of diabodies to
      biotinylated PSA was detected with either polyclonal antimouse Fab F(ab')2 or a
      monoclonal antibody directed against the FLAG epitope. Both detecting antibody
      preparations were covalently labeled with a ruthenium (II) tris (bipyridyl)
      moiety, Ru(bpy)3(2+), which allows quantification via an electrochemically
      triggered light reaction in an ORIGEN analyzer. The binding constants obtained by
      Scatchard analysis of non-linear curve fitting calculations from
      electrochemiluminescence immunoassays were compared with data derived from
      kinetic-binding studies using the BIAcore technology based on surface plasmon
      resonance. Depending on the detecting antibody, the dissociation constants KD
      determined at equilibrium with the ORIGEN technology are between 0.1 and 0.4 nM
      for both diabodies. From the kinetic constants kon and koff measured with the
      BIAcore instrument KD was calculated to be 0.2 nM for P001D and 0.6 nM for P008D.
      It is concluded that these two very different methods generate comparable
      affinity data for the diabodies.

PMID- 9174924
TI  - Studies on oriented and reversible immobilization of glycoprotein using novel
      boronate affinity gel.
AB  - The authors have previously synthesized a novel boronate affinity ligand,
      catechol [2-(diethylamino)carbonyl-4-bromomethyl]phenylboronate. When this ligand
      was coupled to cellulose beads, it bound horseradish peroxidase (HRP), a
      glycoprotein, at pH 7.0. In comparison, commercial m-aminophenylboronic acid
      agarose did not bind HRP below pH 8.0. HRP was immobilized in an oriented and
      reversible fashion using this gel. The immobilized enzyme retained 90.12 per cent
      of its original activity, probably due to its attachment via the carbohydrate
      moiety of the enzyme. After repeated use, the activity remaining on the new gel
      was twice as high as that on conventional m-aminophenylboronic acid-agarose. The
      column was regenerated easily by washing with dilute acid because of
      reversibility of the boronate glycol bond.

PMID- 9174925
TI  - Binding of Escherichia coli LexA repressor to the RecA operator.
AB  - Equilibrium binding of Escherichia coli LexA repressor to the recA operator was
      studied by the polyacrylamide gel mobility shift assay as a function of solution
      conditions. In the presence of NaCl at 20 degrees C, there was a significant salt
      dependence in binding to the recA operator, typical for protein-nucleic acid
      interactions with some electrostatic contribution to the binding free energy. In
      preliminary experiments in which the anion of the Na+ salt was changed from
      chloride to fluoride, little change was found with anion identity. This indicates
      that the salt effect on the binding interaction arises solely from the
      polyelectrolyte effect, not from anion binding or release by the protein upon
      complex formation. Increasing the temperature to 37 degrees C changed the binding
      affinity for complex formation at any given salt concentration and resulted in a
      change in the sensitivity of complex formation to NaCl concentration.
      Quantitative analysis of the data to obtain equilibrium binding constants is
      discussed.

PMID- 9174926
TI  - Development of an immunomagnetic assay system for rapid detection of bacteria and
      leukocytes in body fluids.
AB  - Immunomagnetic (IM) separation and concentration of specific target ligands or
      particles, such as bacteria or leukocytes, from complex mixtures, such as bone
      marrow, blood and other body fluids, is now a widely accepted technique. IM
      methodologies require high affinity antibodies or other receptors, but are
      potentially as effective as density gradient separations. Thus, a computer
      controlled first-generation immunomagnetic assay system (IMAS) biodetector is
      being developed for clinical diagnostics. This system is fully automated and
      affords the advantage of rapid flow-through capture of all types of magnetic
      beads (MBs) and obviates operator contact with body fluid samples during the
      collection and analysis phases. In the present work, biotinylated capture
      antibodies were bound to streptavidin-coated MBs for capture of E. coli O157:H7,
      T cells and T cell subsets. Samples were automatically vortex mixed with antibody
      coated MBs, stained with an acridine dye or fluorescent antibody and collected in
      a specially designed flow cell containing multiple steel pins, which concentrate
      external magnetic field lines. IM complexes were rapidly (within minutes),
      separated from their media in the magnetic field. Magnetically captured particles
      were automatically rinsed in the flow cell to remove unwanted materials and
      detection was achieved via a flow-through fluorimeter. Samples can be
      subsequently captured on a microbiological filter for microscopic visualization
      and image analysis. Preliminary results demonstrate that rapid detection of
      target bacteria and leukocytes at low concentrations in body fluids is possible
      with a total assay time under 1 h. This IM technology has many other potential
      clinical, industrial and environmental monitoring applications.

PMID- 9174927
TI  - Preliminary investigations of an amperometric oligosaccharide dehydrogenase-based
      electrode for the detection of glucose and some other low molecular weight
      saccharides.
AB  - Biosensors for the determination of sugars were constructed using oligosaccharide
      dehydrogenase (ODH) and soluble phenazine methosulfate (PMS) or an osmium-based
      three-dimensional redox hydrogel. In the latter case the enzyme and poly(1
      vinylimidazole) complexed with osmium (4,4'-dimethylbpy)2Cl were cross-linked
      with poly(ethylene glycol) diglycidyl ether. Both electrode configurations showed
      similar sensitivities for glucose in the range between 8 and 21 muAmM-1 cm-2. The
      responses for 10 mono and oligosaccharides were studied. There was no response
      for fructose. In the concentration range 0.1-20 mM the relative sensitivities
      were determined for arabinose (96%), xylose (3%), mannose (50%), galactose (11%),
      glucose (100%), maltose (24%), lactose (12%), cellobiose (34%) and maltotriose
      (10%).

PMID- 9174928
TI  - Immobilization of streptavidin for immunosensors on nanostructured surfaces.
AB  - A modular immunosensor device based on silicon technology with electrochemical
      detection is presented. The sensor surface is functionalized with the antigen
      estradiol using the streptavidin-biotin system. The immobilized antigen is
      recognized by ferrocene-labeled antibody molecules in a competitive assay format.
      The ferrocene redox centers can be detected electrochemically. In order to
      facilitate the electron transfer, a gold layer structured in nanometer dimensions
      is used as an electrode. The functionalized silicon chip will be integrated into
      a micromachined fluid transport system. The resulting immunosensor device for
      estradiol represents a prototype allowing easy adaptation to other biotinylated
      analytes since the immobilized streptavidin serves as a universal anchor.

PMID- 9174929
TI  - Structural characterization and 5'-mononucleotide binding of polyalanine beta
      sheet complexes.
AB  - A study was initiated into the formation and stability of highly soluble beta
      sheet macrostructures. Such beta-sheet macrostructures are useful model systems
      for the study of the biological function of the hydrophobic core of proteins and
      for the de novo design of novel catalytic mimics. In the current study, a 16-mer
      alanine-based peptide (Ac-KA14K-NH2) that is highly water soluble and adopts an
      extremely stable macromolecular beta-sheet structure was synthesized. A tyrosine
      containing analog (Ac-KYA13K-NH1) was used to study the tertiary structure of the
      complex by circular dichroism spectroscopy, while the influence of the charges on
      the complex formation and binding affinity was evaluated using a zwitterionic
      analog (Ac-KEA13KE-NH1). Both the secondary and tertiary structures of the beta
      sheet complex were stable to denaturants, as demonstrated by far- and near
      ultraviolet circular dichroism spectroscopy. Binding studies with mononucleotides
      have shown that the beta-sheet complex binds to molecules through both
      hydrophobic and electrostatic interactions. These intrinsic properties were found
      to be a prerequisite for the observed enhanced cleavage of phosphodiester bonds.

PMID- 9174930
TI  - Immobilized metal-ion affinity chromatography: imidazole proton pump and
      chromatographic sequelae. II. Chromatographic sequelae.
AB  - Isocratic elution with imidazole of some protein models from a chelating gel,
      CSFF-IDA-M(II), resulted in their desorption owing to the low pH(6-->4) of the
      mobile, phase rather than to the imidazole itself (imidazole-generated fall in
      pH; proton pump). Gradient elution with imidazole was best accomplished when the
      chelating gel was initially converted into its imidazole complex, CSFF-IDA
      M(II)Im. The exploitation of the imidazole-generated proton pump in the IMAC of
      proteins may enhance the versatility of this type of chromatography.

PMID- 9174931
TI  - A non-radioactive assay system for screening for inhibitors of RNA-dependent
      reverse transcriptase activity; an analysis using aurintricarboxylic acid and
      plant flavonoids.
AB  - Ongoing and extensive screening for potentially selective and potent inhibitors
      of RNA-dependent DNA polymerases (reverse transcriptases) is important for the
      discovery of therapeutic agents active against retroviruses. Traditional systems
      for assaying the activity of reverse transcriptase enzymes have relied upon the
      use of radioactive nucleotides for monitoring complementary DNA (cDNA) synthesis.
      Moreover, such assays have also typically been programmed by the addition of
      synthetic template-primers. The recent trend, however, is towards the use of more
      natural nucleic acid template-primer-directed systems, which provides for a more
      realistic estimation of the activity of potential therapeutic anti-reverse
      transcriptase agents. A novel agarose gel-electrophoretic method originally
      developed to evaluate DNA polymerase activity during enzyme purification was
      adapted for screening purposes. The system was modified so that one can detect
      the synthesis of non-radioactively labeled cDNA synthesized in both DNA and RNA
      template-directed reverse transcription reactions. Such assays are programmed
      with either M13mp9 single-stranded DNA or rabbit globin mRNA as appropriate
      templates. Following incubation of reaction mixtures, agarose gels are used to
      determine the activity of the DNA-dependent DNA polymerase and RNA-dependent DNA
      polymerase activities of Maloney murine leukemia virus. This is done through a
      detection of the amount of double-stranded nucleic acid molecules (either DNA:DNA
      or RNA:DNA hybrids) generated by the enzyme in the presence and absence of
      various known enzyme inhibitors. The assay systems that have been developed will
      be useful in initial, general, rapid, inexpensive and safer screening programs
      for potential inhibitors of both the DNA- and RNA-dependent DNA-polymerase
      functions of reverse transcriptase enzymes. The system was tested and evaluated
      with potent inhibitors of reverse transcription, such as aurintricarboxylic acid
      and with several plant flavonoids known to be moderately potent inhibitors of
      reverse transcriptases. The details concerning the RNA-dependent DNA polymerizing
      system and some of our results are presented.

PMID- 9174932
TI  - Monitoring fibrinogen adsorption kinetics by interfacial TIRF rheometry.
AB  - The adsorption kinetics of purified fibrinogen to unmodified and
      aminopropylsilane-modified quartz glass surfaces were studied under pseudo-first
      order (binding-unit excess) conditions by the total internal reflection
      fluorescence (TIRF) method. Fluorescence in the adsorbed protein layer (350 nm)
      was excited by the evanescent wave at 285-290 nm. In order to reduce and possibly
      eliminate the influence of mass transfer on the kinetics of fibrinogen
      adsorption, a novel protein adsorption chamber containing a cone-and-plate
      rheometer with total internal reflection technology was employed. The aim of the
      study was to obtain critical shear rates, at which the adsorption rate of
      fibrinogen became independent of diffusion. Therefore, shear rates were varied
      between 0 and 7200 s-1 at initial fibrinogen concentrations of c9 = 4.7 and 17.7
      micrograms mL-1. The adsorption rate of fibrinogen increased 5-17-fold, depending
      on the surface, as the critical shear rate was approached. Above the critical
      shear rates the kinetic data of fibrinogen adsorption could be fitted at c9 = 4.7
      micrograms mL-1 to a single exponential function, indicating the predominance of
      a single binding step with a half-life of ca 20 s. At the higher initial
      concentration of c9 = 17.7 micrograms/mL-, however, a significant deviation from
      the single exponential behavior was observed in the first 10 s of the adsorption
      reaction, indicating a very fast initial event with a half-life of ca 5 s in
      addition to a slower binding reaction with a half-life of ca 35 s. Thus the novel
      TIRF rheometer can resolve kinetics down to half-lives of 5 s and possibly even
      lower.

PMID- 9174933
TI  - Polymer-shielded dye-affinity chromatography.
AB  - Polymer-shielded dye-affinity chromatography is a form of chromatography in which
      the dye matrix forms complexes with a nonionic, water-soluble polymer such as
      poly(vinylpyrrolidone) or poly(vinyl alcohol), prior to the column chromatography
      of a crude protein extract, the idea being that polymer shielding of the dye will
      prevent nonspecific interactions between the target protein and the dye. The
      concept of polymer shielding and a strategy for the rational selection of
      polymers suitable as shielding agents are presented.

PMID- 9174934
TI  - Cyclodextrin-aided capillary electrophoretic separation and laser-induced
      fluorescence detection of polynuclear aromatic hydrocarbons (PAHs).
AB  - Two neutral cyclodextrins (CDs), hydroxypropyl-beta-CD (HP beta OD) and methyl
      beta-CD (M beta CD), and two negatively charged forms, carboxymethyl-beta-CD (CM
      beta CD) and sulfobutylether-beta-CD (SB beta CD), were used to demonstrate the
      principle of separation of hydrophobic and non-charged polynuclear aromatic
      hydrocarbons (PAHs) by capillary electrophoresis (CE) based on differential
      partitioning of analytes between the CDs. The estimation of the partition
      coefficient (Ki) confirmed that the PAH components which partitioned most to the
      negative cyclodextrin (i.e. with the highest Ki) exhibited the longest migration
      time. The Ki values obtained for the CM beta CD-HP beta CD system are all below
      1, indicating that the PAHs prefer to remain in the neutral HP beta CD. The Ki
      values for the SB beta CD-M beta CD buffer are all greater than 1, and cover a
      wider range, indicating preference of the PAHs for the anionic derivative.
      Methods were applied for separation of a PAH mixture containing various important
      PAHs on the US Environmental Protection Agency priority list. This novel
      procedure provided much better separation of PAH isomers, including
      benzo[a]pyrene and benzo[e]pyrene, than has been reported previously using CE.
      The system was applied to the sensitive determination of nanomolar levels of PAHs
      in contaminated soil.

PMID- 9174935
TI  - Single nucleotide modulation of uridine to pseudouridine rearrangement in
      transfer RNA catalyzed by pseudouridine synthase I.
AB  - E. coli pseudouridine synthase I (PSUI) catalyzes the rearrangement of uridine
      residues in positions 38, 39 and 40 of tRNA transcripts to pseudouridine. These
      positions are located in the anticodon stem-loop of the tRNA molecule. Fourteen
      different E. coli tRNAs are substrates for the enzyme, whereas four other tRNAs
      which contain uridine in position 38 are not. Investigations were focused on the
      basis of enzyme differentiation between substrate and non-substrate tRNAs.
      Comparison of modification reactions with mutant and wild-type tRNA transcripts
      demonstrates that the presence of a G36 residue modulates modification by PSUI at
      position 38. In addition to local sequence effects, steady-state kinetic analyses
      suggest the existence of other recognition elements distinct from the immediate
      vicinity of modification.

PMID- 9174936
TI  - Effect of antibody orientation on immunosorbent performance.
AB  - The impact of antibody orientation on immunosorbent efficiency was quantitatively
      assessed. A pH-dependent murine monoclonal antibody (Mab) against human protein C
      (hPC), recombinant hPC (rhPC) and two different immobilization chemistries and
      matrices were used as model systems. The lysyl groups of the rhPC were covalently
      modified with an acetic acid ester of N-hydroxysuccinimide and this modified rhPC
      was used as a Fab masking agent (FMA). The FMA was used to mask the antigen
      binding regions (Fab) of the Mab prior to and during covalent immobilization.
      Thereafter, the residual active sites of the support were inactivated and the FMA
      was removed. Mab was immobilizeed at low bead-averaged densities of about 0.4-1.1
      mg Mab/mL matrix to minimize local density effects. Immunosorbents made using
      masked Mab (oriented coupling) gave antigen binding efficiencies (nAg) of 42-48%
      compared with 18-22% for those made by random coupling. The amount of (Fab)2
      released from pepsin digestion of immunosorbents was about 3-4-fold higher for
      matrices having been made with FMA-masked Mab relative to unmasked Mab. Thus, the
      (Fab)2 accessibility to pepsin correlates well with higher functional efficiency
      (nAg) and serves as a measure of orientation. In summary, at low Mab density and
      a 2:1 molar rhPC to Mab binding stoichiometry, about 80% or more of the Mab
      randomly coupled through amino moieties was improperly oriented relative to
      oriented coupled Mab, which correlated with about 50% of lost Mab functionality
      upon immobilization.

PMID- 9174937
TI  - in vivo targeting of colloidal carriers by novel graft copolymers.
AB  - One of the major obstacles to the targeted delivery of colloidal carriers
      (nanocapsules) is the body's own defence mechanism in capturing foreign particles
      by the reticuloendothelial system (RES). This means that following intravenous
      administration, practically all nanometer size particles are captured by the RES
      (mainly the liver). This paper draws attention to a recent initiative on the
      design of 'macromolecular homing devices' which seem to disguise nanoparticles
      from the RES, and hence are of potential interest for the targeted delivery of
      nanocapsular carriers. The idea is based on a graft copolymer model embodying a
      link site for attachment (binding) to the carrier, a floating pad for maintaining
      the particles afloat in the blood stream, an affinity ligand for site-specific
      delivery and a structural tune for balancing the overall structure of the homing
      device. A general synthetic scheme for the preparation of such graft copolymers
      is given, and preliminary biological evaluations relating to the floating pad
      concept are discussed.

PMID- 9174938
TI  - Dihydrofolate reductase synthesis in the presence of immobilized methotrexate. An
      approach to a continuous cell-free protein synthesis system.
AB  - Dihydrofolate reductase was synthesized in a batch system in the presence of the
      affinity ligand methotrexate, bound to various matrices. Two types of gel were
      used: commercial methotrexate-agarose with pores inaccessible for translation
      machinery and methotrexate-POROS with pores easily accessible for translation
      reaction mixture components. The transcription/translation reaction was not
      inhibited by either the immobilized methotrexate or the matrix. The enzyme was
      synthesized with a high yield and could simultaneously be removed from the
      reaction mixture by the affinity matrix during the synthesis. With methotrexate
      POROS present the reaction probably proceeded mainly in the pores of the gel.
      Kinetic limitations to the reaction in the presence of the gel were not observed.
      Active dihydrofolate reductase was eluted from methotrexate-POROS. The activity
      recovered was higher than dihydrofolate reductase activity synthesized in free
      solution system. The influence of the presence of immobilized methotrexate on
      dihydrofolate reductase synthesis will be further studied in a novel type of a
      continuous protein synthesis system.

PMID- 9174939
TI  - Synthesis and characterization of sol-gel phase-reversible hydrogels sensitive to
      glucose.
AB  - A new type of hydrogel capable of sol-gel phase-reversible transition by changes
      in the environmental glucose concentration has been synthesized. The hydrogel
      consists of vinylpyrrolidinone-allylglucose (VP/AG) copolymer and concanavalin A
      (Con A). The formation of the hydrogel is based on the specific interaction
      between glucose on the copolymer and glucose receptor sites on Con A. Hydrogels
      were formed immediately after mixing the copolymer and Con A. The critical
      factors in the formation of hydrogel were the concentrations of the copolymer, of
      glucose on the copolymer and of Con A. In general, the formation of a hydrogel
      became more efficient as the concentration of glucose on the copolymer decreased
      and/or as the Con A concentration increased. The hydrogel formed became a sol in
      the presence of glucose in the environment. The environmental glucose
      concentration necessary to dissolve the gel to sol was approximately four times
      higher than the concentration of glucose on the copolymer. Upon removal of the
      environmental glucose by dialysis, the sol became a gel again and the sol-gel
      phase transition could be repeated.

PMID- 9174940
TI  - Immobilization of conalbumin onto polystyrene/divinylbenzene co-polymers: towards
      finding the best support for MAMC.
AB  - Immediately after the successful immobilization of conalbumin onto CNBr-activated
      Sepharose, efforts were begun to find a less expensive support and a more benign
      chemistry of activation. The potential of the Sepharose-conalbumin conjugate for
      decontamination of several metal-containing waste-waters has been established,
      and a new method of chromatography has emerged, named metalloprotein affinity
      metal chromatography (MAMC). Efforts to immobilize conalbumin onto
      polystyrene/divinylbenzene co-polymers, using the well known and commercially
      available Merrifield, aminomethyl and plain polystyrene resins are presented
      here. Immobilizations of conalbumin were carried out on the Merrifield and
      Aminomethyl resins, but the procedures were time consuming and complicated by
      polymer aggregation. Because of high cost of these materials, research was
      directed towards the activation and functionalization of plain
      polystyrene/divinylbenzene co-polymers. Chlorosulfonation followed by sulfonamide
      formation was attempted on three commercially available polymers. Successful
      polysulfonamide formation was achieved with bislysine copper(II) acting as a
      diamine. Removal of the copper allows the unblocking of the alpha amino group of
      the immobilized lysine which in turn is treated with glutaraldehyde, affording an
      activated support for immobilization of proteins. To date, approximately 46 mg
      transferrin/g dry matrix have been successfully immobilized. The chemical and
      biological inertness of this support makes it a good candidate to scale up the
      procedure and continue the optimization of MAMC.

PMID- 9174942
TI  - Sequence of bifurcations in an 'antigen-antibody' reaction.
AB  - The aperiodically singularly disturbed system of ordinary differential equations
      describing the process of the formation of the antibody complex initiated by
      antigen binding was analysed. The numerical and analytical examinations showed
      that there are solutions which correspond to primary Hopf bifurcation and
      subsequent finite number of Feigenbaum's period-doubling bifurcations. The last
      leads to chaotization of the system.

PMID- 9174941
TI  - Protein A mimetic peptide ligand for affinity purification of antibodies.
AB  - A peptide mimicking protein A for its ability to recognize the Fc immunoglobulin
      portion has been identified through screening of a synthetic multimeric peptide
      library. Screening of the multimeric library, composed of randomized synthetic
      tripeptide tetramers, has been carried out using a very simple assay, measuring
      the library ability to interfere with the interaction between protein A and
      biotinylated immunoglobulins, monitored on solid phase using an enzyme-linked
      immunosorbent assay format. The tetrameric tripeptide identified after three
      screening cycles was produced in larger amounts and then immobilized in high
      yield on preactivated solid support for the preparation of affinity columns,
      which proved useful for a very convenient one-step purification of antibodies
      directly from crude sera. Antibody purity after affinity purification was close
      to 95 per cent, as determined by densitometric scanning of sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis gels of purified fractions, and up to
      2 mg of antibody could be purified from 1 ml of peptide-derivatized affinity
      support. The ligand was stable to treatment with a vast array of sanitation
      agents, such as ethanol and 0.1 M sodium hydroxide, and to repeated use, thus
      making the ligand applicability extremely attractive for the purification of
      monoclonal antibodies for therapeutic use. Column binding selectivity was similar
      to that of protein A-affinity columns, since immunoglobulin G from several
      sources (rabbit, goat, sheep, mouse) was conveniently purified, with no detection
      of leaked ligand fragments in the purified preparations.

PMID- 9174943
TI  - Application of perfluorocarbons in novel continuous counter-current protein
      chromatography.
AB  - In this work the development of a process capable of extracting proteins from
      particulate-containing solutions (such as fermentation broths) on a continuous
      basis, and in which absorbent and process streams are contacted counter-currently
      is described. The process consists of four stages, required for the loading,
      washing, elution and regeneration of the adsorbent. Because of its counter
      current nature, it has improved performance over existing (though not yet
      commercialized) continuous processes, which have been based on CSTR-type
      contractors (e.g. PERCAS (McCreath et al., 1993). The improved efficiency has
      been shown by carrying out extraction of lysozyme from a single component feed
      stream. The adsorbent used in this work is a Procion Red HE-7B-derivatized
      perfluorocarbon support, which has shown particular suitability for continuous
      processes due to its inherently high mechanical strength and high density.
      Results illustrating yields obtained using this equipment are presented and
      discussed.

PMID- 9174944
TI  - Multiple affinity domains for the detection, purification and immobilization of
      recombinant proteins.
AB  - Affinity systems based on specific molecular recognition are valuable tools for
      detection, purification and immobilization of recombinant proteins. Here, novel
      multipartite affinity fusion vectors were assembled and investigated to allow
      flexible binding and elution conditions. The rationale for the assembly of
      different combinations of affinity domains was to take advantage of the wide
      variety of molecular interactions of these domains for purification,
      solubilization, detection and immobilization. In total, seven different affinity
      tags representing five different types of tag-ligand interactions were studied:
      (i) monoclonal antibodies-peptides (T7-tag and FLAG peptide); (ii) streptavidin
      peptide (Strep-tag); (iii) hexahistidyl-metal ions (His6-tag; (iv) bacterial
      receptors-serum proteins (staphyloccal protein A-Fc and streptococcal protein G
      serum albumin); (v) streptavidin-biotin (in vivo biotinylated peptide). Selected
      tags were evaluated for the production and purification of Escherichia coli DNA
      polymerase I (Klenow fragment). On the basis of the results, a vector (pAff2c)
      was assembled using a novel combination of affinity domains: (i) an in vivo
      biotinylated peptide; (ii) a His6 sequence, and (iii) a highly soluble serum
      albumin binding region. Using these three affinities, a wide variety of
      conditions can be employed for both the binding and the elution steps.

PMID- 9174945
TI  - Intermolecular chiral recognition probed by enantiodifferential excited-state
      quenching kinetics.
AB  - Time-resolved chiroptical luminescence (TR-CL) measurements are used to study the
      kinetics of chirality-dependent excited-state quenching processes in aqueous
      solution. Experiments are carried out on samples that contain a racemic mixture
      of chiral luminophore molecules (L) in solution with a small, optically active
      concentration of chiral quencher molecules (Q). The luminophores are excited with
      a pulse of unpolarized light to create an initially racemic excited-state
      population of lambda L* and delta L* enantiomers, and TR-CL measurements are then
      used to monitor the differential decay kinetics of the lambda L* and delta L*
      subpopulations. Observed differences between the lambda L* and delta L* decay
      kinetics reflect differential rate processes and efficiencies for lambda L*-Q
      versus delta L*-Q quenching actions, and they are diagnostic of chiral
      discriminatory interactions between the luminophore and quencher molecules. In
      this study, the luminophores are either Eu(dpa)3(3-) or Tb(dpa)3(3-) coordination
      complexes (where dpa denotes a dipicolinate dianion ligand), and the quenchers
      are diastereomeric structures of Cr(H2O)4(ATP), Rh(H2O)4(ATP) and Rh(H2O)3(ATP)
      (where ATP identical to adenosine triphosphate). The Ln(dpa)3(3-) (Ln identical
      to En3+ or Tb3+) complexes have three-bladed propeller-like structures of D3
      symmetry, and in aqueous solution they exist as a racemic mixture of left-handed
      (lambda) and right-handed (delta) configurational isomers (enantiomers). The
      results show that the chiral quencher molecules can distinguish between the
      lambda and delta enantiomeric structures of the luminophores in their excited
      state quenching actions. The degree and sense of enantiomeric preference in these
      quenching actions are governed by the electronic and stereochemical properties of
      the quencher molecules. Twenty-one different luminophore-quencher systems are
      examined in this study, and they exhibit interestingly diverse
      enantiodifferential quenching kinetics. The results reflect the extraordinary
      sensitivity of chiral recognition and discrimination processes to relatively
      small, and sometimes subtle, changes in molecular electronic and stereochemical
      structure.

PMID- 9174946
TI  - Affinity adsorption of Saccharomyces cerevisiae on concanavalin A perflurocarbon
      emulsions.
AB  - Perfluorocarbon affinity emulsions have been generated by immobilizing
      concanavalin A onto the surface of triazine-activated perfluorocarbon droplets.
      Immobilized concanavalin A densities of 0.1, 0.7 and 2.1 mg/ml were obtained by
      varying the concentration of cyanuric chloride used for activation. The affinity
      emulsions were found to adsorb Saccharomyces cerevisiae cells from solution with
      adsorption capacities of 1 x 10(9) cells, 4.6 x 10(9) and 6 x 10(9) cell/ml,
      respectively. Optimal conditions for the elution of bound cells were obtained by
      studying inhibition curves of concanavalin A-mannan precipitation using simple
      sugars. Methyl alpha-D-mannopyranoside showed the greatest inhibitory power with
      50 per cent inhibition displayed at a concentration of 0.05 mM. Experiments
      carried out examining the concentrations of methyl alpha-D-mannopyranoside
      necessary to dissociate a concanavalin A-mannan precipitate demonstrated that at
      least a seven-fold higher concentration of methyl alpha-D-mannopyranoside was
      required for dissociation than that required for inhibition of its formation. The
      efficiency of elution of bound yeast cells was found to be dependent on the
      concentration of methyl alpha-D-mannopyranoside used, the time of elution and the
      immobilized ligand density. Thus, 100 per cent elution was obtained with a
      concanavalin A affinity emulsion (0.1 mg/ml) by incubation with 500 mM methyl
      alpha-D-mannopyranoside for 1 h.

PMID- 9174947
TI  - The engineering of biomaterials exhibiting recognition and specificity.
AB  - Although synthetic materials are now widely used in implanted medical devices,
      they are not engineered for recognition and specificity. This article considers
      the design of polymer surfaces that might be specifically recognized and trigger
      normal healing pathways. The technological advances that will contribute to
      biorecognition biomaterials include surfaces to inhibit non-specific
      interactions, self-assembly to create ordered surface structures and strategies
      to place recognition sites on surfaces by random arrays of groups and by
      templates.

PMID- 9174948
TI  - 'Wiring' of lactate oxidase within a low-redox potential electron-conducting
      hydrogel.
AB  - Lactate electrodes based on electron-conducting hydrogels made by cross-linking
      lactate oxidase and the redox polymer formed upon complexing polyvinyl imidazole
      with [Os(dmo-bpy)2Cl]+/2+ (dmo-bpy = 4,4'-dimethoxy-2,2'-bipyridine) on vitreous
      carbon electrode surfaces were investigated. The redox potential of the hydrogels
      was -69 mV, versus the standard calomel electrode (SCE), and their lactate
      electro-oxidation current reached a plateau at +50 mV (SCE). Urate and
      acetaminophen were not electro-oxidized at this potential at rates that would
      interfere with the lactate assays, but ascorbate was catalytically oxidized by
      the gel. At 6 mM lactate concentration, switching of the atmosphere from argon to
      O2, reduced the current by 40 percent, showing that the rate of electron transfer
      from the reduced enzyme to the gel was slow.

PMID- 9174949
TI  - Epitope contiguous chains and antibody recognition in HIV-1 synthetic peptide
      antigens.
AB  - Five peptides derived from human immuno deficiency virus (HIV-1) gp41
      transmembrane protein have been synthesized: M9 (610-618), M12 (598-609), M15
      (600-614), M21 (584-604) and M23 (587-609). These sequences partially overlap in
      the region vicinal to the immunodominant epitope CSGKLIC, between two cysteine
      residues 603-609 and three of them (M12, M15 and M23) include this complete
      heptapeptide. M23, the longer peptide, includes an hydrophilic chain in addition
      to the heptapeptide loop. The purpose of this work was to determine the influence
      of contiguous chains to the heptapeptide loop on antibody recognition in fluid
      and solid phases, and dissociation constants (KD) of each sequence with human
      anti-HIV-1 antibodies. Two peptides, M13 and M23, overlapped on this loop, were
      found to be more reactive. Antigen-antibody dissociation constants were
      determined for both peptides by competition enzyme-linked immunosorbent assay,
      using each peptide alternatively as the solid phase-immobilized antigen. In
      addition to the influence of solid-phase antigen on calculated dissociation
      constants (a phenomenon described by Seligman, 1994), the inhibitory effect of
      M15 in liquid phase on antibody binding to solid phase M23 was higher than
      exerted by M23 in solution over antibody binding to M15 on solid phase. On the
      basis of peptide sequence and predicted antigenicity, this behavior appeared to
      be contradictory. It is assured that the possible origin of this phenomenon is
      due to unfavorable conformation of the longer peptide. Even though synthetic
      peptides mimic mainly sequential epitopes, conformational preferences in fluid or
      solid phase play an important role in epitope functionality. In particular,
      addition of residues to known immunodominant sequences may not always amplify
      antibody recognition if conformation provokes steric hindrance in the native
      epitope.

PMID- 9174950
TI  - Discriminatory recognition of membrane phospholipids by lysine-49-phospholipases
      A2 from Trimeresurus flavoviridis venom.
AB  - Basic proteins I and II (BP-I and BP-II) isolated from Trimeresurus flavoviridis
      venom, which are classified into a group of lysine-49-phospholipases A2 (Lys-49
      PLA2), exhibited only limited lipolytic activity for the mixed micelles of
      various phospholipids. Based on the finding that BP-II elicits a strong
      contraction of guinea pig ileum due to the release of arachidonic acid, BP-II
      together with BP-I has been tested for their interaction with artificial
      phospholipid bilayer membranes. The dye leakage experiments indicated that BP-II
      interacts strongly with liposomes of beta-arachidonoyl-gamma-stearoyl-L-alpha
      phosphatidylcholine. The perturbation of liposomes was observed only in the
      Ca(2+)-containing buffer, and as demonstrated by HPLC analyses, accompanied by
      the release of arachidonic acid. The concentration of Ca2+ which gave a half
      maximal activity of BP-II was 3.0 x 10(-4) M, suggesting that the affinity of BP
      II for Ca2+ is more than 10 times stronger than that of BP-II without liposomes.
      These observations clearly show that Lys-49-PLA2 of BP-II is the enzyme
      responsible for the hydrolysis of membrane phospholipids and that Ca2+ is
      essential for such enzymatic activity. The interaction of BP-I with liposomes was
      much weaker than BP-II BP-I and BP-II share a common sequence except for Asp-67
      (BP-I) and Asn-67 (BP-II) in the aligned sequences. This implies that the amino
      acid at position 67 of Lys-49-PLA2s is the residue required for discriminatory
      recognition of phospholipid membranes.

PMID- 9174951
TI  - Novel method for coupling of poly(ethyleneglycol) to carboxylic acid moieties of
      proteins.
AB  - Lack of toxicity, excellent solubility and superb biocompatibility make
      polyethylene glycol (PEG) one of the most popular modifiers of biologicals. The
      most common method for attachment of PEG is based on modification of amino groups
      of proteins with methoxy- or succinimide-derivatives of PEG. In the case of
      proteins with amino groups important for biological activity, this modification
      can lead to inactivation of proteins. A new strategy for covalent attachment of
      PEG to carboxylic groups of proteins using O,O-bis-(2-aminopropyl)polyethylene
      glycol and carbodiimide/N-hydroxysuccinimide-mediated reaction was developed. The
      reaction is carried out under mild aqueous conditions. The attached PEG serves as
      a hydrophilic spacer for further bioconjungation with biomolecules and haptens.
      Lipase from Candida rugosa was used as a model protein. Characteristic data of
      the modified protein such as activity, isoelectric points and stability were
      compared with that of the unmodified protein.

PMID- 9174952
TI  - Some recent developments in the preparation of novel recognition systems: a
      recognition site for the selective catalysis of an aldol condensation using
      molecular imprinting and specific affinity motifs for alpha-chymotrypsin using a
      phage display peptide library.
AB  - Molecular imprinting and phage display library technologies are rapidly being
      accepted as useful techniques for the generation of ligand-selective recognition
      motifs. The use of molecular imprinting to produce a novel type II aldolase mimic
      selective for the cobalt(II)-mediated aldol condensation of benzophenone and
      acetaldehyde is reported here. Furthermore, peptide motifs have been identified
      which are acting as 'affinity ligands' selective for the recognition of the
      enzyme alpha-chymotrypsin using phage display techniques.

PMID- 9174953
TI  - Biosensors in flow-injection systems for biomedical analysis, process and
      environmental monitoring.
AB  - This paper presents the construction of various biosensors using thin-film layers
      incorporated in flow injection devices, providing automated systems for
      biomedical analysis, process and environmental monitoring. A urease sensor has
      been developed in conjunction with a flow injection system for the automatic
      determination of urea. Use of the spraying immobilization technique gives rise to
      a response time of a few seconds, which allows sample throughputs up to 200 h-1.
      With a penicillin biosensor adapted in an appropriate cell detection, on-line
      measurements of penicillin V in the fermentation broth are achieved during the
      whole fermentation process; the results are compared with the HPLC method.
      Linearity, sensitivity and reproducibility of the biosensor are studied with
      regards to sample dilution in a stirred flow detection cell to provide optimal
      operating conditions. Measurements without any change in parameters are obtained
      during the whole fermentation process. Acetylcholinesterase sensors have been
      used in batch systems for the determination of pesticides, but they require large
      amounts of substrate. When those enzyme sensors are combined with flow injection
      systems, only small volumes (100 microliters) of substrate are injected into the
      carrier stream and an automated system can be obtained for continuous control of
      water quality.

PMID- 9174954
TI  - New technologies for amperometric biosensors.
AB  - Amperomeric-based detectors have successfully been used as personal monitors for
      blood glucose levels. However, there is a desire to increase the number of
      compounds measured in a small blood sample, the speed of detection and enhance
      the reliability of the measurement. Furthermore, with the increasing use of
      microdialysis as a clinical sampling method in metabolic medicine, paediatric
      medicine and neurointensive care, there is a need for rapid on-line detection of
      analytes such as lactate, glucose and glutamate in low microlitre volume samples.
      Two approaches to these problems are described. The first uses enzymes
      immobilized in a packed bed with electrochemical detection of a ferrocene
      mediator as a flow-injection assay for use with microdialysis. Results from
      microdialysis of the brain of freely moving rats are described. In the second
      approach, thin-film techniques are used to fabricate arrays of microdisk and
      micro line electrodes. The properties of these arrays in free solution and in a
      flow cell are presented together with an example using multiple arrays to
      identify an analyte by oxidation potential. Finally, different enzymes are
      entrapped onto the surface of two arrays by electrochemical polymerization of o
      phenylenediamine. The resulting device detects glucose and lactate in real-time.

PMID- 9174956
TI  - Study of the nature of recognition in molecularly imprinted polymers.
AB  - In the present study molecularly imprinted polymers (MIPs) were prepared against
      a series of structurally related compounds containing various numbers of pyridyl
      groups. The goal, to increase understanding of the mechanisms of recognition in
      MIPs, was achieved by comparing the patterns of retention of the imprinted
      compounds on the different MIPs when related to a blank (non-imprinted) polymer
      in a high performance liquid chromatography system. Furthermore, frontal analysis
      was carried out on three polymers: a blank, a pyridine-imprinted and a 4,4'
      bipyridyl-imprinted polymer, to evaluate the number (Bt), average specificity and
      strength (dissociation constant; Kdiss) of the recognition sites. The Kdiss
      values of pyridine on the different polymers were in the range 0.10-0.12 M, and
      the amount of imprinted binding sites (Bt) 0.10-0.12 mmol/g. Kdiss values of 4,4'
      bipyridyl were approximately 0.06 M, with Bt values equal to the above, except
      for in the anti-4,4'-bipyridyl polymer where the Kdiss was determined to be 0.02
      M and Bt 0.07 mmol/g. From the results it can be concluded that multiple additive
      weak interactions dominate the recognition of the template molecules in these
      imprinted polymers.

PMID- 9174955
TI  - Five-membered mercaptoheterocyclic ligands for thiophilic adsorption
      chromatography.
AB  - A series of five-membered mercaptoheterocyles containing at least two heteroatoms
      in their ring structure was investigated for their ability to specifically adsorb
      antibodies. The structures that contain at least one double bond adsorbed
      antibodies, while the saturated structure showed no protein interaction under the
      experimental conditions studied. The influence of various lyotropic salt on
      adsorbance was studied.

PMID- 9174957
TI  - Oriented immobilization of restriction endonuclease EcoRI.
AB  - Two activated matrices have been developed to determine whether immobilization
      chemistry can be used to orient proteins on a support. Restriction endonuclease
      EcoRI from Escherichia coli RY13 (E.C.3.1.23.13) was used as a model in these
      studies. Thiol-activated Sephadex G-10 was used to couple the EcoRI endonuclease
      through its free sulfhydryl, while amino-activated Sephadex G-10 was used to
      couple it randomly through its free carboxyl groups. To determine whether the
      enzyme was immobilized randomly or specifically, both lower and higher molecular
      weight substrates were used. The polymerase chain reaction amplified multiplied
      cloning site region of pBluescript KS obtained using T3 and T7 primers was
      considered as the small substrate. The plasmid SP64 containing firefly luciferase
      gene was the large substrate. Immobilized EcoRI preparations were characterized
      with respect to repeated usage and storage stability. The EcoRI immobilized on
      thiopropyl-Sepharose 4B could be stored for over 14 days at 4 degrees C without
      observable loss of activity. In an independent experiment the same gel was used
      thrice repeatedly without any discernible loss of activity.

PMID- 9174958
TI  - Chiral recognition in adrenergic receptor binding mimics prepared by molecular
      imprinting.
AB  - Molecularly imprinted polymers were prepared against the adrenomimetic agents
      ephedrine and pseudoephedrine. These compounds each incorporate two chiral
      centres. The polymers were evaluated with respect to enantiodiscrimination of
      various adrenergic ligands. The selectivity of the polymeric binding sites for
      the imprinted molecules was very high, and it was found that binding of both the
      enantiomeric and diastereomeric isomers of the imprint species were effectively
      obstructed, it was found that these polymers could selectively recognize the
      enantiomers of the endogenous adrenergic ligand epinephrine as well as several
      beta-adrenergic blockers. These observations suggest that these polymers
      effectively mimic the recognition patterns exhibited by natural adrenergic
      receptors.

PMID- 9174959
TI  - Size-exclusion phases and repulsive protein--polymer interaction/recognition.
AB  - Size-dependent exclusion of macromolecules from gel matrices has long been
      discussed in terms of pore models. An alternate approach is to calculate the
      partition coefficient of the distributed species between the matrix material and
      the mobile phase assuming that the gel can be treated as a polymer solution of
      appropriate concentration and molecular weight. This approach is particularly
      appealing in attempting to predict the behaviour of 'tentacle' phases in which
      the matrix contains anchored linear neutral polymers. The mean field theory of
      polymer solution is used to predict K, the partition coefficient of a polymer
      molecule distributing between the gel and mobile phases. The reduction in entropy
      suffered by the macromolecule in the gel phase is sufficient to produce an
      exponential dependence of K on the molecular weight of the partitioning species.
      The enthalpy of interaction between the gel polymer and the distributed species
      provides a parameter which describes the specificity or recognition in the
      interaction. The predicted linear dependence of in K on protein molecular weight
      is satisfactorily borne out by a data set on eight standard proteins
      chromatographed on four separate gel types.

PMID- 9174960
TI  - Diazotizable supports of potential interest as affinity chromatography matrices.
AB  - Immobilization of affinity ligands, proteins, enzymes and other functional groups
      by azo coupling is based on the high reactivity of the support-carrying diazonium
      groups towards both low- and high-molecular weight compounds containing certain
      groupings such as phenols, imidazole and some other heterocycles, thiols and
      amines. The precursor of diazonium group is a diazotizable amine on the matrix.
      Remarkable progress in its preparation was achieved by application of (4-amino
      phenyl)-(2-sulphatoxyethyl) sulphone-type reagents for functionalization of the
      matrix. A similar type of amine precursor is prepared by the reaction of
      monosubstituted sulphanilamide with epoxide-containing matrix. The presence of a
      SO2 group in the para position to diazonium group of these supports (after
      diazotization) enhances reactivity in azo coupling. 'Reversed' azo coupling is
      the reaction of a matrix containing functional groups capable of reacting with
      diazonium groups of a ligand. Preparation of a suitable matrix and examples of
      diazotizable ligands are given.

PMID- 9174961
TI  - Effect of immobilization on the penicillin binding and reactivity properties of
      DD-peptidase from Streptomyces R61.
AB  - An affinity gel matrix containing an enzyme (DD-peptidase) with specific beta
      lactam binding properties was characterized with respect to its binding and
      reactivity behavior with penicillin. The data show that immobilization of DDP by
      reaction with the enzymes susceptible amino groups resulted in changes in
      catalytic activity on a tripeptide substrate, penicillin binding efficiency and
      pH stability of drug binding. Properties unaffected by immobilization were the
      drug-enzyme complex stability, binding reaction mechanism, drug selectivity and
      method of complex desorption. The affinity of DDP for penicillin-G was
      investigated by surface plasmon resonance. These characteristics were compared
      with those of the soluble enzyme. Conditions for elution of the bound drug were
      determined and a method for immobilizing Streptomyces DDP by which its binding
      site structure is sustained was also evaluated.

PMID- 9174962
TI  - Copper binding studies of lipases from different sources using image binding:
      mechanism of free copper and chelated copper.
AB  - Immobilized metal-ion affinity gel electrophoresis (IMAGE) has been demonstrated
      to be an efficient tool to study the binding of proteins to chelated transition
      metals such as Cu(II). IMAGE was exploited to isolate several lipases from
      different sources and so evaluate their affinities for iminodiacetic acid (IDA)
      Cu(II) and, in particular, to evaluate their enzymatic activities while retained
      on a gel (IMAGE) containing chelated copper [IDA-Cu(II)]. It was found that all
      lipases can be active within the gel while being coordinated to IDA-Cu(II). It is
      concluded that active site histidine (most likely) is not involved in the metal
      recognition and thus other resident histidines serve as electron donors. This is
      mainly attributed to the known phenomenon of occlusion of the catalytic site by
      more or less rigid lid structures. The involvement of active site histidine in
      hydrogen bonding is also evoked.

PMID- 9174963
TI  - Purification and identification of ABA-binding proteins and antibody preparation.
AB  - Maize root membranes were extracted and the solubilized proteins were affinity
      purified using an ABA-BSA-Sepharose 4B matrix. The retained proteins were eluted
      with 4M urea or 10(-4)M ABA. ABA could elute the binding proteins but other
      phytohormones, such as IAA or GA3, could not. ABA binding activity was detected
      in ABA- and urea-elute fractions using competitive ELISA block tests and [3H]ABA
      binding assays. Scatchard analysis showed an apparent K(d) of 4.8 nM for the ABA
      binding activity of the protein. When ABA or urea eluate was loaded on a
      concanavalin-A-Sepharose column, the fraction eluted with 0.2 M methyl alpha
      mannopyranoside still showed ABA binding activity, suggesting that ABA binding
      proteins are glycoproteins. Polyclonal antibodies against ABA binding proteins
      were raised using as immunogen ABA or urea eluate from the ABA-BSA-Sepharose
      column. The resulting antibodies not only recognized 56 kDa binding proteins but
      also blocked the binding of ABA to an ABA-specific antibody, indicating
      properties similar to anti-idiotypic antibodies. The purified antibodies will be
      suitable to purify and characterize putative ABA receptors.

PMID- 9174964
TI  - Well defined dye adsorbents for protein purification.
AB  - When activating a matrix with epichlorohydrin, the degree of activation can be
      controlled by the amount of epichlorohydrin added and the length of time of the
      reaction. The epoxy group can react with thiols and amines to produce N- and S
      linked adsorbents for protein purification. The epoxy-activated gel may also
      react with ammonia to produce an amino-activated adsorbent. This adsorbent reacts
      readily with the reactive groups of textile dyes, coupling the dyes to the matrix
      via a short spacer arm. Conditions can be found where the reaction of the dyes
      with hydroxyl groups on the matrix is minimized, producing dye-ligand adsorbents
      with well defined ligand densities. These dye adsorbents can be made with much
      higher ligand densities than are normally achievable with the conventional
      coupling via hydroxyl groups on the matrix. The protein-binding behaviour of the
      highly substituted adsorbents is qualitatively similar to that of the
      conventional adsorbents but the capacity increases with increase in ligand
      density. Too high a ligand density is undesirable as it may become difficult to
      elute the proteins from the adsorbent. The optimum ligand density was found to be
      between 2 and 10 mumol dye ligand per mL adsorbent, the levels chosen for the low
      and high-dye kits of dye adsorbents for protein purification (Rainbow-sorb).

PMID- 9174965
TI  - Interactions and applications of soluble heterobifunctional affinity chelating
      polymers in immobilized metal affinity chromatography.
AB  - The interaction of immobilized metal-chelating adsorbents with a dual
      heterobifunctional soluble polyethylene glycol (PEG) of the form X-PEG-Y is
      described, where X represents an affinity ligand and Y a chelating agent. The
      bifunctional PEG derivative used in this study was biotin-PEG-iminodiacetic acid
      (IDA). Affinity and metal binding constants of this conjugate for copper and
      avidin were found to be in excellent agreement with the binding affinities of the
      corresponding unconjugated groups IDA and biotin, respectively. The
      characteristics of the interaction of this bifunctional derivative is described
      in terms of its adsorption in immobilized metal affinity chromatographic (IMAC)
      adsorbents. The results show that this derivative can be reversibly and
      selectively bound to specific IMAC adsorbents under certain experimental
      conditions. This immobilized scheme resembles a system where an IMAC adsorbent
      was transformed into an affinity adsorbent as a result of the interactions of
      both chelating derivatives, one in solution (biotin-PEG-IDA) and the other on the
      solid matrix (IMAC adsorbent). Apparently the modified IMAC adsorbents, once the
      affinity chelating ligands are attached, exhibit characteristics similar to those
      of covalently bound affinity ligands in affinity chromatographic systems.

PMID- 9174966
TI  - Analysis of antibody selection by phage display utilizing anti-phenobarbital
      antibodies.
AB  - The generation of new antibodies for diagnostic applications using phage display
      could greatly decrease the time and expense of new assay development but, to be
      effective, the process must yield antibodies with desired specificity and
      affinity comparable to those obtained by monoclonal antibody technology. In order
      to evaluate the ability of the phage selection process to yield antibodies with
      the desired specificity and affinity, a family of anti-phenobarbital antibodies
      were cloned as scFvs and Fabs and displayed on M13 gene III fusion proteins. All
      of the antibodies are derived from similar germline VL and VH genes and exhibit
      extensive sequence homology except in VH CDR3. Despite these similarities, the
      range of panning efficiencies was observed to vary by two orders of magnitude for
      expressed scFvs. Unexpectedly, the scFv with the highest panning efficiency has
      the lowest affinity. In competitive panning experiments this scFv is
      preferentially isolated over higher affinity antibodies. This scFv expresses high
      levels of soluble binding protein while higher affinity scFvs express lower
      levels of protein or nonfunctional protein. These results suggest that the
      efficiency of functional expression of scFv proteins can greatly influence the
      type of antibody selected by phage display. The range of panning efficiency for
      functional Fabs was significantly less (four-fold) than that observed for scFvs
      and did not correlate to the expression level of the secreted proteins. Based on
      the results of the Fabs examined, it is concluded that the expression properties
      of Fabs may not exhibit the extent of variability observed for scFvs when
      displayed and use of an Fab architecture may provide an advantage over scFv
      architecture in the selection process. The feasibility of selecting against
      undesirable cross-reactivities has also been demonstrated by simple modification
      of phage panning conditions. These combined results support the concept of
      obtaining antibodies with desirable specificity and affinity for diagnostic
      applications through the use of phage display.

PMID- 9174967
TI  - Purification of an expressed insect transferrin from cell culture media using
      high-capacity Ni(2+)-dipicolylamine gel.
AB  - Vertebrate transferrin is a well characterized iron transport protein. In
      contrast, little is known concerning the role of transferrin in insects. Yet,
      study of iron metabolism in insects could give insights into strategies for
      insect control, particularly for insects that transmit disease.

PMID- 9174968
TI  - End point attached heparin affinity matrix.
AB  - Heparin is a highly sulfated long-chain glycosaminoglycan utilized extensively
      for its anticoagulation properties, which has found widespread use as a general
      affinity ligand. The polysaccharide is composed of repeating units of uronic acid
      and glucosamine with great variability in sequence within the chain. The high
      degree of sulfation imparts strong acidity to the molecule and it may bond with
      many compounds simply by ionic interaction. In addition, it has been established
      that heparin contains certain specific monosaccharide sequences which act as
      unique binding sites for some proteins. For utilization as a biospecific affinity
      ligand it has been reported that heparin may optimally be immobilized by a single
      point of attachment through a terminal sugar residue. This method of
      immobilization allows unrestricted access to sequences within the polysaccharide
      chain required for biospecific interaction. Heparin immobilized to beaded agarose
      by single point attachment through its terminal formyl moiety was prepared.
      Chromatographic performance characteristics were evaluated using thrombin and
      antithrombin III as model compounds and elution profiles are presented.
      Additionally, stability of attachment was directly compared to several other
      commercially available supports. In conclusion, this end-point attached affinity
      matrix demonstrates high capacity and good stability compared with that of other
      methods of preparation.

PMID- 9174969
TI  - Mechanisms of cardiovascular activity of Andrographis paniculata in the
      anaesthetized rat.
AB  - The cardiovascular activities of crude water extract (WE) of Andrographis
      paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate
      (FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a
      major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD)
      rats for the very first time. FA and andrographolide, which possesses multiple
      pharmacological activities, elicited no drop in mean arterial blood pressure
      (MAP), while WE, FB and FC produced a significant fall in MAP in a dose-dependent
      manner without significant decrease in heart rate. The ED50 values for WE, FB and
      FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These suggested that the
      hypotensive substance(s) of the crude water extract was concentrated in FB.
      Pharmacological antagonist studies were consequently only tested in FB (5 mg/kg).
      The hypotensive action of FB was not mediated through effects on the beta
      adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme,
      for it was not affected by propranolol, atropine and captapril, respectively.
      However, it seems to work via alpha-adrenoceptors, autonomic ganglion and
      histaminergic receptors, since the hypotensive effect of FB was negated or
      attenuated in the presence of phentolamine, hexamethonium as well as pyrilamine
      and cimetidine.

PMID- 9174971
TI  - The effect of NaO Li Su on memory functions and blood chemistry in elderly
      people.
AB  - In traditional Chinese medicine a mixture of bee pollen, radix polygoni
      multiflore, semen ziziphi spinosae, radix salviae multiorhizae, fructus
      schisandrae and fructus ligustris lucidae, known as NaO Li Su, has a reputation
      as a remedy against declining memory functions. In the present study the effect
      of the preparation on failing memory was assessed in 100 elderly Danish
      volunteers who complained of a deteriorating memory. The study was a double-blind
      placebo controlled cross-over trial. The effect was evaluated after treatment
      periods of 3 months' duration by a battery of psychological and biochemical
      tests. No desirable effects on memory functions were achieved by the active
      treatment. Increases in the number of red blood cells and in the serum creatinine
      levels were seen after active treatment. In the subgroup initially showing a
      number of red blood cells below the median a significant positive correlation was
      found between changes in the number of red blood cells and changes in the
      Wechsler Memory Scale scores.

PMID- 9174970
TI  - The antioxidant activity of Chinese herbs for eczema and of placebo herbs--I.
AB  - A standardized mixture of Chinese herbs has recently been demonstrated to be an
      effective treatment for chronic atopic eczema in placebo controlled trials in the
      UK. Aqueous decoctions of this formulated mixture (PSE 222), the placebo mixture,
      and their component herbs were examined for antioxidant activity to determine
      whether antioxidant activity could account for the anti-eczema activity. Two
      measures of antioxidant activity were employed: the DPPH assay for non-specific
      hydrogen atom (or electron) donating activity and a superoxide scavenging assay.
      Antioxidant activity was detected in some components of both the active and
      placebo mixtures, but the formulated active mixture (PSE 222) was significantly
      more effective than the formulated placebo mixture. Further studies are needed to
      elucidate the in vivo significance of this result.

PMID- 9174972
TI  - Biological studies of Bolax gummifera, a plant of the Falkland Islands used as a
      treatment of wounds.
AB  - Aqueous and dichloromethane extracts of Bolax gummifera (Lam.) Sprengel
      (Apiaceae), a plant of the Falkland Islands used as a treatment of wounds, were
      studied in order to support the ethnopharmacological information related to the
      medicinal use of this plant. The antimicrobial, antioxidant and red blood cells
      membrane stabilizing activities were analyzed. The antimicrobial bioassay was
      carried out using the test turbidity method (OD 620 nm), the aqueous extract
      showing an 82% inhibition of Staphylococcus aureus but no activity against
      Pseudomonas aeruginosa. The dichloromethane extract inhibited both
      microorganisms: S. aureus in 94% and P. aeruginosa in 32%. No antioxidant
      activity could be observed using hydroperoxide-initiated chemiluminescence in rat
      liver homogenates. Investigations into the membrane stabilizing activity of the
      extracts were carried out using human red blood cells subjected to hypotonic- and
      heat-induced lyses. The aqueous extract showed an important stabilizing activity
      of the red blood cell membrane.

PMID- 9174973
TI  - The Chinese herbal medicine, shinpi-to, inhibits IgE-mediated leukotriene
      synthesis in rat basophilic leukemia-2H3 cells.
AB  - We examined the action of Shinpi-To (Formula divinita; TJ-85), a granular extract
      of seven Chinese medicinal herbs that is used in treating childhood asthma, on
      the leukotriene synthesis in rat basophilic leukemia-2H3 cells (RBL-2H3 cells).
      IgE-loaded cells were stimulated with anti-IgE serum in the presence or absence
      of Shinpi-To. Released LTC4 and LTB4 were measured by radioimmunoassay (RIA).
      Shinpi-To significantly inhibited IgE-mediated synthesis of leukotriene (LT)C4
      and LTB4. To identify the inhibitory sites, we investigated the action of this
      extract on four synthetic enzymes, phospholipase A2 (PLA2), 5-lipoxygenase (5
      LO). LTC4 synthase, and LTA4 hydrolase. Shinpi-To inhibited the A23187-stimulated
      release of [3H]arachidonic acid (AA) from the cell membrane, reflecting an effect
      on PLA2 activity. It also suppressed production of LTC4 and LTB4 when cell
      lysates were incubated with AA as substrate. It did not inhibit the production of
      LTC4 and LTB4 when LTA4-free acid was used as the substrate. Shinpi-To did not
      inhibit the IgE-mediated increase of intracellular Ca2+ ([Ca2+]i) concentration.
      Results indicate that Shinpi-To inhibits LT synthesis by inhibiting PLA2 and 5-LO
      activities without affecting the mobilization of [Ca2+]i.

PMID- 9174974
TI  - Antiplasmodial activity of four Kenyan medicinal plants.
AB  - A preliminary antiplasmodial and phytochemical screening of four Kenyan medicinal
      plants was carried out. The medicinal plants were extracted and tested for in
      vitro antiplasmodial activity against chloroquine-sensitive (K67) and chloroquine
      resistant (ENT36) strains of Plasmodium falciparum. Out of 16 extracts, 12 were
      active against ENT36 strain while seven were active against K67 strain, that is,
      IC50 < or = 50 micrograms/ml. The most active extracts on both strains were those
      of leaves of Phyllanthus reticulatus Poir, and Suregada zanzibariensis Baill.
      (Euphorbiaceae) with IC50 < or = 10 micrograms/ml. The stembark of Terminalia
      spinosa Engl. (Combretaceae) and the stems of Dissotis brazzae Cogn.
      (Melastomataceae) had IC50 < or = 10 micrograms/ml for strains K67 and ENT36,
      respectively. A preliminary phytochemical analysis of these plants revealed the
      presence of different classes of primary and secondary metabolites.

PMID- 9174975
TI  - Wound healing activity of Leucas lavandulaefolia Rees.
AB  - Leucas lavandulaefolia Rees (Labiatae), commonly known as Halkusha, is a well
      known plant in Indian traditional medicine. On the basis of its traditional use
      and literature references, this plant was selected for evaluation of its wound
      healing potential. A methanol extract of L. lavandulaefolia was examined for its
      wound healing activity both in the form of an ointment as well as an injection in
      two types of wound model in rats: (i) the excision wound model and (ii) the
      incision wound model. Both the injection and the ointment of the methanol extract
      of the plant material produced a significant response in both of the wound types
      tested. The results were also comparable to those of a standard drug,
      nitrofurazone, in terms of wound contracting ability, wound closure time, tensile
      strength and regeneration of tissues at the wound site.

PMID- 9174976
TI  - Anti-inflammatory activity of Salacia oblonga Wall. and Azima tetracantha Lam.
AB  - The anti-inflammatory activity of Salacia oblonga rootbark powder and Azima
      tetracantha leaf powder was assayed in male albino rats using carrageenan-induced
      rat paw oedema (acute inflammation) and cotton pellet granuloma (chronic
      inflammation) methods. Both the crude drugs were maximally active at a dose of
      1000 mg/kg. In the cotton pellet granuloma assay, these drugs were able to
      suppress the transudative, exudative and proliferative components of chronic
      inflammation. Furthermore, these drugs were able to lower the lipid peroxide
      content of exudate and liver, gamma-glutamyl transpeptidase activity in the
      exudate of cotton pellet granuloma. The increased acid and alkaline phosphatase
      activity and decreased serum albumin in cotton pellet granulomatous rats were
      normalised after treatment with these drugs. It is likely that these drugs may
      exert their activity by antiproliferative, antioxidative and lysosomal membrane
      stabilization.

PMID- 9174977
TI  - Depletion of tumor necrosis factor-alpha in mice by Nyctanthes arbor-tristis.
AB  - The effect of the water soluble fraction of the ethanol extract of Nyctanthes
      arbor-tristis (NAT) on tumor necrosis factor-alpha (TNF-alpha) level in plasma of
      arthritic and soluble protein A (SpA)-treated Balb/c mice has been studied. Oral
      administration of this fraction in arthritic mice showed a consistent depletion
      of TNF-alpha from the host plasma. A similar depletion of TNF-alpha in the plasma
      of SpA-treated mice has been observed. The extract also reduces plasma interferon
      gamma level but the plasma IgM and IgG levels are not affected. The implications
      of these observations are discussed in the light of management of TNF-alpha in
      clinical disorders.

PMID- 9174978
TI  - Antiviral activity of galangin isolated from the aerial parts of Helichrysum
      aureonitens.
AB  - The in vitro antiviral activity of galangin (3,5,7-trihydroxyflavone), the major
      antimicrobial compound isolated from the shoots of Helichrysum aureonitens, was
      investigated against herpes simplex virus type 1 (HSV-1), coxsackie B virus type
      1 (Cox B1), adenovirus type 31 (Ad31) and reovirus. At concentrations ranging
      from 12-47 micrograms/ml galangin showed significant antiviral activity against
      HSV-1 and CoxB1, limited activity against reovirus, and no antiviral activity
      against Ad31.

PMID- 9174979
TI  - Protective effect of Rhinax, a herbal formulation, against CCl4-induced liver
      injury and survival in rats.
AB  - Rhinax, a herbal formulation, was investigated for its protective activity
      against CCl4-induced liver injury and survival in rats. Oral administration of
      Rhinax at a dose of 80 mg/kg significantly reduces the hepatotoxic effects of
      CCl4. It also significantly improves the survival of rats at a dose of 160 mg/kg.
      On the basis of these observations, we conclude that Rhinax possesses anti
      hepatotoxic activity and that the observed activity may be due to the increased
      activity of cytochrome P450, thereby exerting an inhibitory effect on reductive
      pathways of CCl4.

PMID- 9174980
TI  - Antibodies to a synthetic peptide that react with flavin-containing monooxygenase
      (HLFMO3) in human hepatic microsomes.
AB  - Flavin-containing monooxygenases (FMOs) catalyze the oxidation of a diverse array
      of xenobiotic compounds. The purpose of this investigation was to develop a
      specific immunological probe to human hepatic flavin-containing monooxygenase
      (HLFMO3). An oligopetide corresponding to amino acid residues 257-270 of HLFMO3
      was coupled to keyhole limpet hemocyanin (KLH) through the sulfhydryl group of a
      cysteine residue added to the amino-terminus of the peptide. This peptide-KLH
      conjugate was used to generate a polyclonal antibody. The resulting
      immunoglobulin showed specific Western blot reactivity with HLFMO3 protein in
      human hepatic microsomes, the same protein that is recognized by a polyclonal
      antibody directed against macaque liver FMO. These findings demonstrate that an
      antibody directed against a synthetic peptide derived from HLFMO3 can be easily
      produced in large quantities and used in studies for the immunodetection and
      immunoquantification of HLFMO3. This is also the first antipeptide antibody
      directed against an FMO of any species.

PMID- 9174981
TI  - Improved high-performance liquid chromatographic procedure for the separation and
      quantification of hydroxytestosterone metabolites.
AB  - A reproducible, sensitive high-performance liquid chromatography (HPLC) method
      has been developed to quantify hydroxytestosterone metabolites. The method
      features a simple one-step linear gradient of methanol in water (10%-60%
      methanol) for separation of the testosterone metabolites on a Supelcosil LC-18
      column; metabolites are detected at 247 nm. This method provides a distinct
      advantage over previously developed assays in that the solvent gradient does not
      contribute to baseline changes throughout the chromatographic run. In this way,
      the flat baseline markedly improves robustness of the assay and simplifies peak
      integration and quantification. At the same time, resolution of 15 different
      steroid metabolites catalyzed by the cytochrome P-450 enzymes are readily
      separated in rat or mouse liver microsomes. An internal standard, cortexolone,
      was selected for use based on its structural and spectral similarity to the
      hydroxytestosterone metabolites, and quantification is based on the molar
      response for the testosterone/cortexolone peak area ratio. The limit of detection
      (LOD) is 1 pmol on-column with a limit of quantitation (LOQ) of 4 pmol on-column.
      The intraday repeatability is approximately 3%. This simplified procedure is
      straightforward and should greatly facilitate the routine use of the testosterone
      hydroxylation assay to measure cytochrome P-450 isozyme activity.

PMID- 9174982
TI  - Analysis of buprenorphine in rat plasma using a solid-phase extraction technique
      and high-performance liquid chromatography with electrochemical detection.
AB  - A solid-phase extraction method and sensitive reversed phase high-performance
      liquid chromatography analysis with electrochemical detection of buprenorphine
      and its metabolite, norbuprenorphine, in rat plasma is described. Adequate
      separation of the compounds of interest was achieved on a Phenomenex C18 reversed
      phase column using a mobile phase comprising phosphate buffer: acetonitrile
      (75:25, pH 3.0) and 0.25 mM 1-octane-sulfonic acid, at a flow rat of 1 ml/min.
      Electrochemical detection was performed at a potential of 0.75 V and sensitivity
      of 2 nA. Buprenorphine and norbuprenorphine were extracted from plasma by solid
      phase extraction technique using naltrindole as an internal standard (IS).
      Recoveries of buprenorphine and norbuprenorphine following the extraction method
      were high (70%-89%) over the concentration range used (25-100 ng/ml) and no
      endogenous substances in plasma interfered with any of the sample components. The
      retention times for norbuprenorphine, IS, and buprenorphine were 8, 12.5, and
      30.5 min, respectively. The limits of detection of buprenorphine and
      norbuprenorphine in spiked plasma samples were 25 and 5 ng/ml, respectively.
      Using this method, buprenorphine was detected in rat plasma in animals acutely
      treated with the drug (5 mg/kg, s.c.).

PMID- 9174983
TI  - Limitation of Hu-PBL-scid mouse model in direct application to immunotoxicity
      assessment.
AB  - Hu-PBL-scid mice were directly introduced to the methods of immunotoxicity
      assessments. Human IgG and IgM was detected 1 week after transplantation.
      Cyclosporin A (CsA) and cyclophosphamide (CP), which were injected i.p. 4 weeks
      after transplantation, decreased the serum concentration of IgM after 2-4 days of
      treatment but not that of IgG. Lymphocyte proliferation induced by various
      mitogens and primary T-dependent antibody responses to sheep red blood cells
      could not be measured by using splenocytes of hu-PBL-scid mice. These results
      were correlated with the fact that human cells were not detected in the spleen,
      thymus, or blood of hu-PBL-scid mouse but were detected in lymph nodes of the
      intestine, which were observed by flow cytometric and immunohistochemical
      examinations. The present results suggest using hu-PBL-scid mice in routine
      immunotoxicity investigations: lymph nodes of intestines could be used as the
      lymphocyte source. In addition, the determination of serum Ig concentration might
      be used as a experimental item.

PMID- 9174984
TI  - Use of type I and type IV hypersensitivity responses to define the
      immunopharmacological profile of drugs.
AB  - Administration of antigen suspended in incomplete Freund's adjuvant supplemented
      with either heat-killed Mycobacterium tuberculosis (complete Freund's adjuvant,
      CFA) or Bordetella pertussis toxin sensitizes animals so that subsequent antigen
      challenge leads to delayed-type (DTH) or immediate type hypersensitivity (ITH)
      responses, named type IV and type I, respectively. Appropriate timing of
      administration of drugs with respect to immunization or antigen challenge allowed
      to detect predominantly immunosuppressive, antiinflammatory or antianaphylactic
      activities. Among the reference drugs tested, only cyclosporin A (CsA) and
      dexamethasone (Dex) markedly inhibited DTH reaction, due to their
      immunosuppressive and antiinflammatory activities, respectively, whereas
      leflunomide and indomethacin resulted less potent. On the other hand, only
      dexchlorpheniramine, a histamine-receptor antagonist, afforded significant
      protection against anaphylactic shock, a form of ITH. Two new chemical entities
      were studied according to this protocol: ITF 1697, a chemically stabilized C
      reactive protein-derived tetrapeptide, and ITF 2018, a leflunomide analogue. Data
      obtained with these new compounds showed that ITF 1697 has antianaphylactic
      activity, while ITF 2018 is endowed, mainly, with antiinflammatory activity.
      These results show that, through appropriate timing of administration,
      established in vivo models of immunologically mediated disease states allow an
      accurate profiling of the effects of pharmacologically active molecules and the
      detection of unsuspected activities for new drugs.

PMID- 9174985
TI  - Evaluation of an electrochemical microprobe for direct NO measurement in the rat
      gastric fundus.
AB  - Nitric oxide (NO) is an inhibitory nonadrenergic, noncholinergic (NANC)
      neurotransmitter in the rat gastric fundus and is released upon electrical or
      pharmacological stimulation of the inhibitory NANC neurons. In this study, it was
      attempted to measure the release of NO from the rat gastric fundus upon
      electrical stimulation or administration of nicotine directly via an
      electrochemical probe (ISO-NO). The system was evaluated by adding exogenous NO.
      Addition of exogenous NO induced concentration-dependent relaxation of the rat
      gastric fundus and an increase in the ISO-NO probe baseline current. The
      concentration of NO detected by the ISO-NO probe was lower than the concentration
      of NO administered. When no tissue was present, higher concentrations of NO were
      detected than in the presence of a tissue. In the absence of 95% O2/5% CO2 the
      concentration of NO detected was highest. Electrical stimulation induced
      relaxations of the rat gastric fundus which were reduced by NG-nitro-L-arginine
      methylester (L-NAME). An increase in the ISO-NO probe baseline current was also
      observed, but this was duc to nonspecific effects as the response also occurred
      without a tissue present and was not sensitive to L-NAME. Nicotine induced
      relaxations, which were reduced by L-NAME, but the ISO-NO probe baseline current
      remained unaltered, even in the presence of L-arginine plus superoxide dismutase.
      It can be concluded that it is not possible to detect directly the NO release
      from the rat gastric fundus upon electrical or pharmacological stimulation of the
      NANC neurons with the ISO-NO probe.

PMID- 9174986
TI  - Determination of the mechanism of action of anticancer drugs by means of the
      computer-assisted microscope image analysis of Feulgen-stained nuclei.
AB  - The antitumoral effects of 30 drugs was monitored in vitro on three neoplastic
      cell lines. These 30 drugs belonged to various pharmacological classes which
      included alkylating agents, antimetabolites, Vinca alkaloids, topoisomerase II
      inhibitors, and intercalating agents. The aim of the present work is to use the
      same methodology to characterize the drug-induced effects at several biological
      levels. The drug-induced modifications were, therefore, monitored by means of the
      digital cell image analysis of Feulgen-stained nuclei. This methodology enabled
      the cell cycle kinetics to be studied. Furthermore, the numerical data
      quantitatively describing chromatin patterns were submitted to multivariate
      (principal-components) analyses, with the canonical transformation of the data.
      Statistical analysis shows that each pharmacological class of anticancer drugs
      induces specific modifications to the chromatin patterns. The present study,
      therefore, shows that it is possible to identify distinct classes of
      antineoplastic drugs on the basis of their mechanisms of action by means of the
      quantitative chromatin pattern description of Feulgen-stained nuclei.

PMID- 9174987
TI  - Using Bisico S4i for electrodes and peripheral nerve embedding.

PMID- 9174988
TI  - Force generation in muscle: time-resolved measurements of ATPase activity using a
      phosphate-sensitive fluorophore.

PMID- 9174989
TI  - Measurement of sarcoplasmic reticulum Ca2+ content and sarcolemmal Ca2+ fluxes in
      isolated rat ventricular myocytes during spontaneous Ca2+ release.
AB  - 1. Intracellular calcium concentration ([Ca2+]i) and Na(+)-Ca2+ exchange currents
      were measured in calcium-overloaded voltage-clamped rat ventricular myocytes
      loaded with the Ca(2+)-sensitive fluorescent indicator indo-1. Sarcoplasmic
      reticulum (SR) Ca2+ content was measured from the integral of the caffeine-evoked
      current. In cells that had spontaneous SR Ca2+ release in 1 mM external Ca2+
      concentration ([Ca2+]o)i raising [Ca2+]o increased the frequency of release with
      no effect on SR Ca2+ content. In quiescent cells, increased [Ca2+]o produced
      spontaneous Ca2+ release associated with increased SR Ca2+ content. Further
      increase of [Ca2+]o had no effect on SR Ca2+ content. The amount of Ca2+ leaving
      the cell during each release was constant over a wide range of frequencies and
      [Ca2+]o values. It appears there is a maximum level of SR Ca2+ content, perhaps
      because spontaneous Ca2+ release results when the content reaches a threshold. 2.
      From the relationship between [Ca2+]i and Na(+)-Ca2+ exchange current during a
      caffeine response, it is possible to estimate the changes in Na(+)-Ca2+ exchange
      current expected from a change of [Ca2+]i. The data show that the calcium
      oscillations contribute a significant fraction of the total extra Ca2+ efflux
      induced by increasing [Ca2+]o. Raising [Ca2+]o decreased the rate of calcium
      removal from the cell as measured from the rate of decay of the caffeine
      response, suggesting that both inhibition of Ca2+ efflux and increased Ca2+ entry
      account for the Ca2+ overload at elevated [Ca2+]o. 3. Inhibiting spontaneous SR
      Ca2+ release increases resting [Ca2+]i. The Ca2+ efflux is identical to that in
      the presence of release. It is concluded that spontaneous release of calcium,
      although potentially arrhythmogenic, is an effective way to activate Ca2+ efflux
      in overloaded conditions and minimizes any increase of diastolic tension.

PMID- 9174990
TI  - The effect of Ca(2+)-calmodulin-dependent protein kinase II on cardiac excitation
      contraction coupling in ferret ventricular myocytes.
AB  - 1. The effect of Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) on
      excitation-contraction coupling (E-C coupling) was studied in intact ferret
      cardiac myocytes using the selective inhibitor KN-93, KN-93 decreased steady
      state (SS) twitch [Ca2+]i (by 51%), resting Ca2+ spark frequency (by 88%) and SS
      sarcoplasmic reticulum (SR) Ca2+ content evaluated by eaffeine application (by
      37.5%). 2. Increasing extracellular Ca2+ concentration ([Ca2+]o) to 5 mM in KN-93
      restored SR Ca2+ load and Ca2+ spark frequency towards that in control (2 mM
      Ca2+o), but SS twitch [Ca2+]i was still significantly depressed by KN-93. 3. KN
      93 decreased Ca2+ transient amplitude of SS twitches much more strongly than the
      amplitude of post-rest (PR) twitches. In the control, the time constant (Tau) of
      [Ca2+]i decline of SS twitches was faster than that for PR twitches. This
      stimulation-dependent acceleration of [Ca2+]i decline was abolished by KN-93. 4.
      Voltage-clamp experiments demonstrated that KN-93 significantly inhibited
      sarcolemmal L-type Ca2+ current (ICa) during repetitive pulses by slowing
      recovery from inactivation. This may explain the preferential action of KN-93 to
      suppress SS vs. PR twitches. 5. In KN-93, even when both ICa and SR Ca2+ load
      were matched to the control levels by manipulation of conditioning voltage-clamp
      pulses, contraction and twitch Ca2+ transients were still both significantly
      depressed (to 39 and 49% of control, respectively). 6. Since KN-93 reduced SR
      Ca2+ release channel (RyR) activity during E-C coupling, even for matched SR Ca2+
      load and trigger ICa, we infer that endogenous CaMKII is an important modulator
      of E-C coupling in intact cardiac myocytes. Effects of KN-93 on ICa and SS twitch
      [Ca2+]i decline also indicate that endogenous CaMKII may have stimulatory effects
      on ICa and SR Ca2+ uptake.

PMID- 9174991
TI  - Electrogenic K+ transport by the Na(+)-K+ pump in rat cardiac ventricular
      myocytes.
AB  - 1. The involvement of electrogenic reaction steps in K+ transport by the Na+,
      K(+)-ATPase was determined in rat cardiac ventricular myocytes using whole-cell
      patch clamp techniques. 2. Under K(+)-K+ exchange conditions and in the presence
      of extracellular K+ or Tl+ at concentrations that stimulated submaximal levels of
      steady-state Na+,K(+)-ATPase activity, ouabain-sensitive transient currents were
      observed during ('on') and after ('off') step changes in membrane potential (Vm).
      3. The quantity of charge moved during the transient currents depended, in a
      saturable manner, on the magnitude of the voltage step. Maximal ouabain-sensitive
      'on' and 'off' charges were calculated to be 9.6 +/- 0.9 and 9.1 +/- 0.4 fC pF-1
      (n = 4), respectively, with an effective valeney of 0.48 +/- 0.07 (n = 7). 4.
      Kinetics of the transient currents were independent of Vm and Tl+o at positive
      potentials, but became more rapid at increasingly negative Vm values in an ion
      concentration-dependent fashion. 5. Those data demonstrate that electrogenic
      steps participate in K+ transport by the Na+,K(+)-ATPase and that the
      electrogenic step is extracellular ion binding. 6. The temperature- and Vm
      dependent properties of transient charge movements were compared under K(+) -K+
      and Na(+) -Na+ exchange conditions. The data suggest that extracellular K+ and
      Na+ binding occur at different sites in the enzyme or to different enzyme
      conformations. The sum of the effective valencies, 1.14 +/- 0.12, demonstrates
      that the electrogenicity of extra-cellular ion binding can explain the Vm
      dependence of ion transport by the Na+,K(+)-ATPase.

PMID- 9174992
TI  - Opposing effects of phorbol esters on transmitter release and calcium currents at
      frog motor nerve endings.
AB  - 1. Phorbol esters activate protein kinase C (PKC) and also increase the secretion
      of neurotransmitter substances by an unknown mechanism. To evaluate whether the
      stimulatory effects of such agents on acetylcholine (ACh) secretion occur as a
      consequence of stimulation of Ca2+ entry, we made electrophysiological
      measurements of ACh secretion (i.e. endplate potentials, EPPs) and the component
      of the prejunctional perineural voltage change associated with nerve terminal
      calcium currents (perineural calcium current) at frog neuromuscular junctions. 2.
      In the first series of experiments, modest concentrations of K+ channel blockers
      were employed so that simultaneous measurements of EPP amplitudes and perineural
      calcium currents could be made. In these experiments, 12-O-tetradecanoylphorbol
      13-acetate (TPA; 162 nM) and phorbol 12,13-dibutyrate (PDBu; 100-200 nM) each
      increased ACh release but simultaneously decreased the calcium component of the
      prejunctional perineural current TPA and PDBu also inhibited perineural calcium
      currents in the presence of higher concentrations of K+ channel blockers. 3.
      Blockade of Ca2+ channels by Cd2+ prevented the action of PKC stimulators on
      perineural waveforms. 4. The inactive compound 4-alpha-phorbol 12-myristate 13
      acetate (150 nM) did not affect EPP amplitudes or perineural currents. 5. The
      extracellular [Ca2+]-ACh release relationship was increased in maximum by PDBu
      without any change in the potency of Ca2+ to support evoked ACh release. 6. The
      results demonstrate that phorbol esters increase neurotransmitter secretion
      whilst simultaneously decreasing the nerve ending calcium currents that promote
      evoked release. The results, which suggest that the optimal control point for
      secretion might not be the calcium channel but rather a component of the
      secretory apparatus, are discussed in conjunction with the possible target sites
      for phorbol esters in the nerve ending.

PMID- 9174993
TI  - Developmental changes in isolated rat type I carotid body cell K+ currents and
      their modulation by hypoxia.
AB  - 1. Whole-cell patch-clamp recordings were used to investigate possible age
      related changes in K+ currents of type 1 carotid body cells isolated from the
      rat. K+ current density increased with age, as measured in cells isolated from 4
      day-old, 10-day-old and adult rats (> or = 5 weeks old). 2. The proportion of
      current reversibly inhibited by high [Mg2+] (6 mM), low [Ca2+] (0.1 mM)
      solutions, indicative of the proportion of current attributable to activation of
      Ca(2+) -sensitive K+ (KCa) channels, was significantly smaller in cells of 4-day
      old rats compared with 10-day-old rats, despite inward Ca2+ current densities
      being similar in these two age groups. Inhibition of K+ currents by high [Mg2+],
      low [Ca2+] solutions was similar in 10-day-old and adult type 1 cells. 3. Hypoxia
      (PO2, 16-23 mmHg) caused reversible reductions in type I cells from rats of all
      age groups. However, reductions seen in cells of 4-day-old rats were
      significantly smaller than those seen in cells of 10-day-olds and adults. The
      degree of hypoxic inhibition in these latter two groups was not significantly
      different. 4. In the presence of high [Mg2+], low [Ca2+] solutions, hypoxia (PO2,
      16-23 mmHg) was without significant effect on residual K+ currents in cells from
      all age groups. 5. These observations indicate that K+ current density increases
      with postnatal age in the rat. Between days 4 and 10, there appears to be a
      predominant enhancement of KCa channels, and over the same age range hypoxic
      sensitivity of K+ currents increases. Our findings demonstrate that this latter
      observation arises because hypoxia selectively inhibits KCa channels in cells at
      all ages studied. These results suggest an important role for KCa channels in
      postnatal maturation of hypoxic chemoreception in the rat carotid body.

PMID- 9174994
TI  - Activation of a novel non-selective cation channel by alloxan and H2O2 in the rat
      insulin-secreting cell line CRI-G1.
AB  - 1. Alloxan and its auto-oxidation product hydrogen peroxide (H2O2) irreversibly
      depolarize insulinoma cells by opening a non-selective cation channel. The
      channel opened is characterized by a linear current-voltage relation with a
      conductance of approximately 70 pS and very slow kinetics (of the order of
      seconds). 2. Cells are protected against the alloxan-induced channel opening and
      consequent cell depolarization by the presence of H2O2 and hydroxyl radical
      scavengers. 3. The free radical-activated non-selective cation channel is not
      operative in isolated patches but can be activated by the application of beta
      NAD+ to the cytoplasmic aspect of the membrane.

PMID- 9174995
TI  - Modulation by adenosine of GABA-activated current in rat dorsal root ganglion
      neurons.
AB  - 1. The modulation by adenosine of GABA-activated current (IGADA) was studied in
      freshly isolated rat dorsal root ganglion (DRG) neurons using the whole-cell
      patch-clamp technique. 2. In most of the DRG neurons examined (68/90, 75.5%)
      adenosine (1-10 microM) suppressed IGABA, while in some neurons examined, it
      potentiated (16/90, 17.8%) IGABA. It exerted no effects on IGABA in a few cells
      (6/90, 6.7%). 3. Adenosine shifted the GABA concentration-response curve downward
      with no significant change of the EC50. The maximal response to GABA was
      suppressed by 29.6 +/- 2.6%. The adenosine-induced inhibition of IGABA showed no
      voltage dependence. 4. 8-Cyclopentyl-1,3-dimethylxanthine (DPCPX; 1 microM), a
      selective A1 adenosine receptor antagonist, partially reversed adenosine
      inhibition of IGABA and completely blocked N6-cyclo-hexyladenosine (CHA; an A1
      adenosine receptor agonist) inhibition of IGABA. DPCPX (1 microM) also blocked
      the suppression of IGABA by 2-chloroadenosine (CADO). CGS21680, a selective A2A
      adenosine receptor agonist, did not inhibit IGABA and DMPX, a selective A2A
      adenosine receptor antagonist, did not prevent adenosine inhibition of IGABA. 5.
      Intracellular application of H-7 (20 microM; a protein kinase C inhibitor)
      reversed adenosine inhibition of IGABA while inclusion of cAMP (1 mM), H-9 (20
      microM; a protein kinase A inhibitor) and BAPTA (10 mM; a chelator of calcium
      ions) in the recording pipette did not affect the depression of IGABA by
      adenosine. IGABA was also suppressed by internal perfusion of PMA, a protein
      kinase C activator. 6. The results suggest that adenosine, as a neuromodulator,
      exerts a modulatory effect on the GABA-induced presynaptic inhibition in primary
      sensory transmission.

PMID- 9174996
TI  - Dendritic and somatic glutamate receptor channels in rat cerebellar Purkinje
      cells.
AB  - 1. The properties of glutamate receptor (GluR) channels in outside-out patches
      from the dendrites and somata of rat cerebellar Purkinje cells in brain slice
      were studied using fast agonist application techniques. Dendritic patches were
      isolated 40-130 micronm from the soma. 2. Outside-out patches from both dendrites
      and somata of Purkinje cells responded to application of glutamate with a current
      which desensitized rapidly and nearly completely. Currents evoked by glutamate
      application were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), were
      mimicked by L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and
      were modulated by cyclothiazide. Kainate produced small, non-desensitizing
      currents. No currents were observed in response to aspartate application.
      Responses characteristic of NMDA receptor activation were not observed. These
      findings indicate that glutamate-activated currents were mediated by the AMPA
      subtype of GluR. 3. Deactivation of the GluR channels following 1 ms pulses of
      glutamate occurred with a time constant of 1.23 +/- 0.07 ms in dendritic and 1.12
      +/- 0.04 ms in somatic patches. Desensitization occurred with a time constant of
      5.37 +/- 0.26 ms in dendritic and 5.29 +/- 0.29 ms in somatic patches. The time
      constant of recovery from desensitization caused by a 1 ms application of 1 mM
      glutamate was 36 ms in dendritic patches and 33 ms in somatic patches. 4. Half
      maximal activation of the GluR channels was achieved at a glutamate concentration
      of 432 microM. Deactivation kinetics were not dependent on the glutamate
      concentration, while desensitization became slower at lower glutamate
      concentrations. 5. Pre-equilibration of patches with low concentrations of
      glutamate reduced the peak current activated by 1 mM glutamate. The IC50 for this
      effect was 8.7 microM. Equilibrium desensitization did not affect the kinetics of
      the current activated by 1 mM glutamate. 6. The current-voltage relationship of
      the peak current was linear in normal Na(+)-rich external solution, with a
      reversal potential near 0 mV. In Ca(2+) -rich external solution, the reversal
      potentials were -51.4 +/- 2.9 and -51.5 +/- 2.8 mV for dendritic and somatic
      patches, respectively, indicating that these glutamate channels have a low
      permeability to Ca2+ (PCa/PCa = 0.053). 7. The mean single-channel conductance of
      the GluR channels measured using non-stationary fluctuation analysis was
      approximately 8 pS in dendritic and somatic patches, and the maximum open
      probability was at least 0.7 with 5 mM glutamate. 8. GluR channel kinetics in
      patches excised from the soma of neonatal (postnatal day 4; P4) Purkinje cells,
      before the development of the dendritic arborization of the Purkinje cell, were
      similar to those in patches excised from more mature (P12-18) Purkinje cells. 9.
      Dendritic and somatic GluR channels in Purkinje cells appear to be functionally
      identical, are AMPA-subtype receptors containing the GluR-B subunit, and have
      rapid kinetics and low permeability to Ca2+. A kinetic model was constructed
      which faithfully reproduces the gating characteristics of the GluR channels.

PMID- 9174997
TI  - Effect of hydroxylamine on photon-like events during dark adaptation in toad rod
      photoreceptors.
AB  - 1. The suction pipette technique was used to investigate the recovery of toad rod
      photoreceptors following small bleaches of 0.2-3% of the rhodopsin. 2. The
      reduction in sensitivity and the increase in noise elicited by bleaches were
      measured, and from these measurements the underlying rate of occurrence of photon
      like events was calculated as a function of time after the bleach. 3. Exposure to
      hydroxylamine solution was used to hasten the decomposition of the metarhodopsin
      photoproducts. The outer segment was exposed to 110 mM hydroxylamine in a low
      Ca2+ Ringer solution for a period of 10-50 s beginning 10-17 min after the
      bleaching exposure. 4. By the time of the hydroxylamine exposure, the flash
      sensitivity and response kinetics had returned almost to normal, and were not
      significantly altered by the exposure. 5. Following hydroxylamine exposure, the
      rate of spontaneous photon-like events in the rods declined rapidly to near pre
      bleach levels. 6. We conclude that hydroxylamine reduces the rate of occurrence
      of photon-like events induced by a bleach, and we postulate that this reduction
      results from the removal of metarhodopsin (most likely metarhodopsin II) from the
      outer segment. 7. Our results are consistent with a model in which photon-like
      events result from reversal of the reactions (phosphorylation and capping by
      arrestin) that lead to inactivation of the activated form of rhodopsin, Rh*.

PMID- 9174998
TI  - The effects of calcium buffering and cyclic AMP on mechano-electrical
      transduction in turtle auditory hair cells.
AB  - 1. The effects of intracellular Ca2+ buffering on hair cell mechanotransduction
      were studied in an intact cochlear epithelium where the endolymphatic and
      perilymphatic surfaces could be separately perfused with different Ca2+
      solutions. 2. The speed and extent of transducer adaptation increased as the
      concentration in the patch electrode of the Ca2+ buffer BAPTA was lowered. In 0.1
      mM BAPTA or less, the transducer adapted almost completely, with a mean time
      constant of 0.8 ms. 3. For a fixed internal BAPTA concentration, the transducer
      conductance varied with hair cell location, increasing towards the high-frequency
      end of the cochlea, and the time constant of adaptation decreased proportionally.
      At a given cochlear location, hair cells with larger transducer conductances
      displayed faster adaptation. We suggest that transducer adaptation accounts for a
      variable high-pass filter observed in the acoustic tuning curve. 4. The effects
      of perfusion of 50 microM Ca2+ endolymph depended on the BAPTA concentration of
      the electrode: with 3 mM BAPTA, adaptation was abolished, but in most recordings
      with 0.01 or 0.1 mM BAPTA, rapid adaptation was retained. The current
      displacement curve was also shifted less the lower the intracellular BAPTA
      concentration. Cells in the high-frequency half of the papilla retained
      adaptation at a higher BAPTA concentration. 5. Treatment with the cAMP agonist, 8
      bromo-cAMP, or with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine,
      caused a rightward shift in the current-displacement curve which was independent
      of the internal BAPTA concentration. 6. We conclude that the free Ca2+ and cyclic
      nucleotide concentrations of the hair bundle modulate the position of the
      activation curve of the transducer. The factors which may be important for the
      correct functioning of adaptation in vivo are discussed.

PMID- 9174999
TI  - ATPase kinetics on activation of rabbit and frog permeabilized isometric muscle
      fibres: a real time phosphate assay.
AB  - 1. The rate of appearance of inorganic phosphate (Pi) and hence the ATPase
      activity of rabbit psoas muscle in single permeabilized muscle fibres initially
      in rigor was measured following laser flash photolysis of the P3-1-(2
      nitrophenyl)ethyl ester of ATP (NPE-caged ATP) in the presence and absence of
      Ca2+. Pi appearance was monitored from the fluorescence signal of a Pi-sensitive
      probe, MDCC-PBP, a coumarin-labelled A197C mutant of the phosphate-binding
      protein from Escherichia coli. Fibres were immersed in oil to optimize the
      fluorescence signal and to obviate diffusion problems. The ATPase activity was
      also measured under similar conditions from the rate of NADH disappearance using
      an NADH-linked coupled enzyme assay. 2. On photolysis of NPE-caged ATP in the
      presence of Ca2+ at 20 degrees C, the fluorescence increase of MDCC-PBP was non
      linear with time. ATPase activity was 41 s-1 in the first turnover based on a
      myosin subfragment 1 concentration of 150 microM. This was calculated from a
      linear regression of the fluorescence signal reporting 20-150 microM of Pi
      release. Tension was at 67% of its isometric level by the time 150 microM Pi was
      released. ATPase activities were 36 and 31 s-1 for Pi released in the ranges of
      150-300 microM and 300-450 microM, respectively. The ATPase activity had a Q10
      value of 2.9 based on measurements at 5, 12 and 20 degrees C. 3. An NADH-linked
      assay showed the ATPase activity had a lower limit of 12.7 s-1 at 20 degrees C.
      The response to photolytic release of ADP showed that the rate of NADH
      disappearance was partially limited by the flux through the coupled reactions.
      Simulations indicated that the linked assay data were consistent with an initial
      ATPase activity of 40 s-1. 4. On photolysis of NPE-caged ATP in the absence of
      Ca2+ the ATPase activity was 0.11 s-1 at 20 degrees C with no discernible rapid
      transient phase of Pi release during the first turnover of the ATPase. 5. To
      avoid the rigor state, the ATPase rate in the presence of Ca2+ was also measured
      on activation from the relaxed state by photolytic release of Ca2+ from a caged
      Ca2+ compound, nitrophenyl-EGTA. At 5 degrees C the ATPase rate was 5.8 and 4.0 s
      1 in the first and second turnovers, respectively. These rates are comparable to
      those when NPE-caged ATP was used. 6. The influence of ADP and Pi on the ATPase
      activities was measured using the MDCC-PBP and NADH-linked assays, respectively.
      ADP (0.5 mM) decreased the initial ATPase rate by 23%. Pi (10 mM) had no
      significant effect. Inhibition by ADP, formed during ATP hydrolysis, contributed
      to the decrease of ATPase activity with time. 7. The MDCC-PBP assay and NPE-caged
      ATP were used to measure the ATPase rate in single permeabilized muscle fibres of
      the semitendinosus muscle of the frog. At 5 degrees C in the presence of Ca2+ the
      ATPase activity was biphasic being 15.0 s-1 during the first turnover (based on
      180 microM myosin subfragment 1). Tension was 74% of its isometric level by the
      time 180 microM Pi was released. During the third turnover the ATPase rate
      decreased to about 20% of that during the first turnover. 8. ATPase activity in
      isometric rabbit muscle fibres during the first few turnovers is about an order
      of magnitude greater than that when a steady state is reached. Possible reasons
      and the consequences for understanding the mechanism of muscular contraction are
      discussed.

PMID- 9175000
TI  - Detachment of low-force bridges contributes to the rapid tension transients of
      skinned rabbit skeletal muscle fibres.
AB  - 1. To probe the cross-bridge cycle and to learn more about the cardioplegic agent
      BDM (2,3-butanedione monoxime), its effects on the force-velocity properties and
      tension transients of skinned rabbit muscle fibres were studied at 1-2 degrees C
      and pH 7.0. 2. Three millimolar BDM decreased isometric force by 50%, velocity by
      29%, maximum power by 73%, and stiffness by 25%, so that the relative stiffness
      (stiffness/force ratio) increased by 50% compared with reference conditions in
      the absence of BDM. 3. Tension transients obtained under the reference condition
      (0 BDM) could be represented by three components whose instantaneous stiffness
      accounted for the initial (Phase 1) force deviation and whose exponential
      recoveries caused the rapid, partial (Phase 2) force recovery following the step.
      The fastest component had non-linear extension-force properties that accounted
      for about half the isometric stiffness and it recovered fully. The two slower
      components had linear extension-force properties that together accounted for the
      other half of the sarcomere stiffness. These components recovered only partially
      following the step, producing the intermediate (T2) level which the force
      approached during Phase 2. 4. Matching the force transients obtained under test
      conditions (3 mM BDM) required three alterations: (1) reducing the amplitude of
      the two slower components by 50%, in proportion to isometric force, (2) adding a
      non-relaxing component and (3) decreasing the amplitude of the rapidly recovering
      component by 12.5% so that its relative amplitude (amplitude/isometric force) was
      increased by 75%. The non-recovering component and the increase in relative
      amplitude of the rapid component were responsible for the increase in relative
      stiffness of the fibres produced by BDM. The rapidly recovering component had the
      same time constant and step-size-dependent recovery rates as the fastest of the
      three mono-exponential components isolated from the tension transient response
      under the reference condition. BDM therefore appeared to augment the fastest
      component of the tension transient under the reference condition. 5. The results
      suggest that BDM detains cross-bridges in low-force, attached states. Since these
      bridges are attached, they contribute to sarcomere stiffness. Since they are
      detained, relaxation or reversal of their immediate responses is probably due to
      bridge detachment rather than to their undergoing the power stroke. The
      observation that a portion of the test response matched the fastest component of
      the reference response when the amplitude of the fastest component was increased
      suggests that a part of the normal rapid, transient tension recovery following a
      release step is due to detachment of low-force bridges moved to negative-force
      positions by the step.

PMID- 9175001
TI  - On-going and reflex synaptic events in rat superior cervical ganglion cells.
AB  - 1. Synaptic events evoked by brief noxious cutaneous stimuli were recorded in
      sympathetic neurones in the superior cervical ganglion of anaesthetized rats. 2.
      On-going excitatory synaptic potentials (ESPs) and/or action potentials (APs)
      were recorded in 69% of neurones at mean frequencies that varied from 0.01 to 6.3
      Hz in different cells. From histograms of ESP amplitude during membrane
      hyperpolarization, it appears that most cells received one (52%), or two or more
      (36%), suprathreshold inputs and several subthreshold inputs with overlapping
      amplitudes. 3. Pinching the skin for 1-3 s evoked either a brief burst of
      synaptic events (lasting about 300 ms) preceding a few seconds of inhibition
      (burst-inhibitory (BI) neurones), or simply an excitation (excitatory (E)
      neurones), or no response (O neurones). In 60% of BI neurones, a second burst
      occurred after the end of the pinch. 4. BI neurones had a higher frequency of on
      going synaptic activity (2.9 +/- 0.5 Hz, n = 15) than E neurones (0.2 +/- 0.1 Hz,
      n = 5) or O (0.2 +/- 0.1 Hz, n = 5) neurones. Most neurones with two or more
      suprathreshold inputs were BI neurones. In 20% of neurones (all BI with high
      rates of synaptic activity), several other inputs had ESPs with amplitudes close
      to threshold. 5. Subthreshold and suprathreshold inputs responded in the same way
      in only 45% of neurones, but suprathreshold inputs were excited in 73% of BI and
      all E neurones. The order of recruitment of different inputs varied from trial to
      trial. If classification was based only on suprathreshold responses, there were
      36% BI, 32% E and 32% O neurones. 6. In the majority of neurones, postganglionic
      discharge was initiated exclusively by suprathreshold inputs, even during reflex
      excitation. 7. Qualitatively similar, but smaller, responses were evoked by a
      puff of air on the abdomen in 71% of cells tested. 8. The data suggest that the
      natural discharge of SCG neurones is largely determined by the activity of one or
      two preganglionic inputs with high quantal contents. BI neurones may include
      vasoconstrictor neurones, whereas the other types include secretomotor, pilomotor
      and other neurones projecting to targets in the head.

PMID- 9175002
TI  - Spike-evoked suppression and burst patterning in dorsal root ganglion neurons of
      the rat.
AB  - 1. A low level of spontaneous impulse discharge is generated within dorsal root
      ganglia (DRGs) in intact animals, and this activity is enhanced following nerve
      injury. Many physiological stimuli present in vivo are capable of augmenting this
      ectopic discharge. Whatever their cause, episodes of sharply accelerated DRG
      firing tend to be followed by 'after-suppression' during which discharge falls
      below baseline rate. In this study we examined the process of postexcitation
      suppression of firing rate, and how it shapes spike patterning in primary sensory
      neurons. 2. We recorded intracellularly from sensory neurons in excised rat DRGs
      in vitro. Trains of spikes triggered by intracellular current pulses evoked a
      prolonged hyperpolarizing shift. This shift appeared to be due to activation of a
      Ca(2+)-dependent K+ conductance (9K(Ca)). Spikes evoked by just-suprathreshold
      pulses triggered a hyperpolarizing shift and spike cessation. As the shift
      decayed, spiking was restored. The net result was bursty (on-off) discharge, a
      previously unexplained peculiarity of ectopic discharge in some DRG neurons in
      vivo. 3. Conditioning nerve tetani delivered to axons of neurons which share the
      DRG with the impaled neuron evoked transient depolarization ('cross
      depolarization'). However, when stimulus strength was increased so as to include
      the axon of the impaled neuron, the net result was a hyperpolarizing shift. Nerve
      stimulation that straddled the threshold of the axon of the impaled neuron drove
      it intermittently, but it always drove axons of at least some neighbouring
      neurons. The result was dynamic modulation of the membrane potential of the
      impaled neuron as cross-depolarization and spike-evoked hyperpolarizing shifts
      played off against one another. Membrane potential shifted in the hyperpolarizing
      direction whenever the axon was activated, and shifted in the depolarizing
      direction whenever it was silent. Dynamic modulation of this sort probably also
      occurs in vivo when stimuli are drawn over the surface of the skin.

PMID- 9175003
TI  - Excitatory and inhibitory motor reflexes in the isolated guinea-pig stomach.
AB  - 1. We have described and analysed the movements of the isolated stomach during
      distension by correlating intragastric pressure with video recordings, and
      investigated the presence of intrinsic inhibitory and excitatory reflexes. 2.
      Isolated guinea-pig stomachs, placed in an organ bath, were slowly distended with
      Krebs solution using a syringe pump via a cannula through the pylorus. The
      changes in intragastric pressure during cycles of distension were monitored by
      pressure transducers connected to both oesophageal and pyloric cannulae. The
      resistivity of the gastric wall (change in pressure with volume, delta P/delta V)
      and the amplitude and frequency of phasic pressure events were calculated from
      pressure recordings. 3. The movements of the stomach were also recorded onto
      videotape. The motion of the gastric wall during distension cycles was analysed
      to establish the patterns of contractions, their propagation and the distribution
      of fluid in the stomach. During filling, fluid was preferentially accommodated in
      the fundus. Propagating (peristaltic) contractions, often starting in the fundus,
      moved aborally towards the pylorus. The peak of the phasic pressure event was
      observed when a contraction reached the orad antrum. As it reached the pylorus,
      intragastric pressure was at its minimum. 4. During the initial phase of
      distension, intragastric pressure increased steeply. Tetrodotoxin and hyoscine
      reduced both the resistivity and amplitude of phasic pressure events.
      Hexamethonium had a similar effect. Thus distension appears to activate an
      excitatory reflex pathway, involving nicotinic ganglionic transmission. This
      reflex increases wall tension and enhances myogenic peristaltic contractions. 5.
      In control preparations, with larger distension volumes, the intragastric
      pressure decreased, despite the continued infusion of Krebs solution. L-NAME and
      apamin abolished this drop in pressure, indicating that gastric enteric
      inhibitory mechanisms prevail at larger distension volumes. After blockade of the
      excitatory reflex, hexamethonium antagonized the inhibitory response, indicating
      that activation of inhibitory mechanisms involves nicotinic transmission,
      probably on enteric inhibitory motoneurons. 6. Both the excitatory and inhibitory
      reflexes in the isolated stomach operate within a physiological range of gastric
      volumes. The excitatory reflex predominates at small distension volumes, leading
      to large phasic propagated contractions that mix the contents and may lead to
      emptying of the stomach. The inhibitory reflex, described previously as adaptive
      relaxation, can maximally relax the stomach and is activated preferentially at
      higher distension volumes to accommodate the contents. The interplay of these
      reflex pathways in the isolated stomach produces a rich repertoire of gastric
      movements. 7. The isolated stomach preparation, used with a combination of
      kinematic, kinetic and pharmacological methods, provides a highly suitable means
      of investigating the mechanisms of gastric motility.

PMID- 9175005
TI  - Coherent oscillations in monkey motor cortex and hand muscle EMG show task
      dependent modulation.
AB  - 1. Recordings were made of local field potential (slow waves) and pyramidal tract
      neurone (PTN) discharge from pairs of sites separated by a horizontal distance of
      up to 1.5 mm in the primary motor cortex of two conscious macaque monkeys
      performing a precision grip task. 2. In both monkeys, the slow wave recordings
      showed bursts of oscillations in the 20-30 Hz range. Spectral analysis revealed
      that the oscillations were coherent between the two simultaneously recorded
      cortical sites. In the monkey from which most data were recorded, the mean
      frequency of peak coherence was 23.4 Hz. 3. Coherence in this frequency range was
      also seen between cortical slow wave recordings and rectified EMG of hand and
      forearm muscles active during the task, and between pairs of rectified EMGs. 4.
      The dynamics of the coherence were investigated by analysing short, quasi
      stationary data segments aligned relative to task performance. This revealed that
      the 20-30 Hz coherent oscillations were present mainly during the hold phase of
      the precision grip task. 5. The spikes of identified PTNs were used to compile
      spike-triggered averages of the slow wave recordings. Oscillations were seen in
      11/17 averages of the slow wave recorded on the same electrode as the triggering
      spike, and 11/17 averages of the slow wave recorded on the distant electrode. The
      mean period of these oscillations was 45.8 ms. 6. It is concluded that
      oscillations in the range 20-30 Hz are present in monkey motor cortex, are
      coherent between spatially separated cortical sites, and encompass the pyramidal
      tract output neurones. They are discernable in the EMG of active muscles, and
      show a consistent task-dependent modulation.

PMID- 9175004
TI  - Energetic cost of activation processes during contraction of swine arterial
      smooth muscle.
AB  - 1. The objective of this study was to partition the increase in ATP consumption
      during contraction of swine carotid arterial smooth muscle estimated from
      suprabasal oxygen consumption (suprabasal JO2) and lactate release (Jlactate)
      into a component associated with cross-bridge cycling (JX) and one reflecting
      activation (JA). 2. Two experimental approaches-varying length under constant
      activation, and varying activation at a long length (1.8 times the optimal length
      for force development (Lo)) where force generation is minimal-revealed a linear
      dependence of JO2 and activation energy (JA) on cross-bridge phosphorylation.
      Protocols inducing a large increase in myosin regulatory light chain (MRLC)
      phosphorylation at 1.8 Lo resulted in significant elevations of JO2 and marked
      reductions in the economy of force maintenance. Our evidence suggests that this
      is primarily due to the increased cost of cross-bridge phosphorylation. 3. The
      extrapolated estimate of JA during maximal K(+)-induced depolarization made by
      varying length was 16%, while at 1.8 Lo it was 33% of the suprabasal JO2 at Lo.
      Calculated activation energies ranged from 17 to 45% of the suprabasal JO2 at Lo
      and from 72 to 87% of the suprabasal JO2 at 1.8 Lo under stimulation conditions
      that varied steady-state MRLC phosphorylation from 15 to 50%. 4. The results
      suggest that the kinetics of cross-bridge phosphorylation-dephosphorylation can
      rival those of cross-bridge cycling during isometric contractions in swine
      arterial smooth muscle.

PMID- 9175006
TI  - The effects of chronic hypoxia on renal function in the rat.
AB  - 1. Studies were performed on rats that had been made chronically hypoxic (CH
      rats) in a normoxic chamber at 12% O2 for 3-5 weeks. Under Saffan anaesthesia,
      respiratory and cardiovascular variables, renal haemodynamics and renal function
      were recorded while the rats spontaneously breathed 12% O2 followed by a switch
      to air breathing for 20 min. Plasma renin activity was assessed by
      radioimmunoassay of angiotensin I. Plasma atrial natiruetic peptide (ANP) was
      indirectly assessed by measurement of cyclic GMP in urine. 2. When breathing 12%
      O2, CH rats showed hyperventilation and raised haematocrit (52%) relative to
      normoxic (N) rats. But arterial pressure (ABP), renal blood flow (RBF), renal
      vascular conductance (RVC), mean right atrial pressure (mRAtP), urine flow,
      glomerular filtration rate (GFR) and absolute sodium excretion (UNaV) were
      comparable to those recorded in N rats breathing air. Urinary cGMP was 40%
      greater than in N rats, but plasma renin activity was not significantly greater
      in CH than in N rats. 3. Air breathing in CH rats induced hypoventilation, a 12%
      increase in ABP, no change in mRAtP, RBF or GFR, but increases of 75 and 100% in
      urine flow and UNaV, respectively. Neither urinary cGMP nor plasma renin activity
      changed. Such increases in urine flow and UNaV were absent when renal perfusion
      pressure (RPP) was prevented from rising during air breathing by using an
      occluder on the dorsal aorta. 4. We propose that by 3-5 weeks of chronic hypoxia
      renal function was normalized, principally because arterial O2 content was
      normalized by the increase in haematocrit and because ABP and renal haemodynamics
      were normalized: acute hypoxia in N rats produces a fall in ABP. We suggest that
      plasma ANP was raised by the actions of hypoxia or erythropoietin on the atrium,
      rather than by atrial distension, but suggest that ANP had little direct
      influence on renal function and tended to limit the influence of the renin
      angiotensin system. We further propose that the diuresis and natriuresis seen
      during air breathing were mediated by the increase in RPP; neither plasma ANP nor
      renin activity change in the immediate short term.

PMID- 9175007
TI  - Enterotropic mouse hepatitis virus.
AB  - Mouse hepatitis virus [MHV], the coronavirus of the mouse, is the most common
      viral pathogen in contemporary laboratory mouse colonies throughout the world. It
      is highly contagious with variable clinical manifestations. The majority of
      infections are subclinical, but can still significantly influence biological
      responses, thus interfering with research, mainly in the field of immunology. MHV
      has been intensively studied from a number of research perspectives and has
      become the prototype for studying the molecular biology of coronaviruses. MHV
      contains a single-stranded, positive-sense RNA genome ranging from 27 to 31 kb,
      which is divided into seven genes. Virions consist of four to five structural
      proteins. There are many MHV strains that vary in virulence, organotropism and
      cell tropism, and are constantly evolving by naturally occurring mutation and
      recombination. Based on pathogenesis studies MHV strains are usually grouped
      according to their primary tissue tropism into two biotypes: polytropic and
      enterotropic. Enterotropic strains of MHV replicate in the intestinal mucosa and
      only rarely spread to other tissues. No morphological structure of the virion has
      as yet been identified that is responsible for enterotropism. The course of an
      MHV infection is dependent on the virus strain and host factors. Generally, MHV
      causes an acute, self-limiting infection which is inapparent in adult mice.
      Neonates are highly susceptible to disease and show high mortality. In an
      enzootically infected colony, however, they are protected by maternally derived
      passive immunity. Detection of MHV infections depends on serological screening of
      colonies. MHV is controlled by culling and rederivation of the affected colony
      using hysterectomy or embryo transfer or by elimination through cessation of
      breeding.

PMID- 9175008
TI  - Happy animals make good science.
AB  - In this paper the question is posed whether it is not only better for the animal
      to be happy, but whether its state of mind may also have the potential to
      influence the scientific results derived from it. To ensure good science, the
      animal should have a normal physiology and behaviour, apart from specific adverse
      effects under investigation. There is a growing body of evidence from a wide
      variety of sources to show that animals whose well-being is compromised are often
      physiologically and immunologically abnormal and that experiments using them may
      reach unreliable conclusions. On scientific, as well as ethical grounds,
      therefore, the psychological well-being of laboratory animals should be an
      important concern for veterinarians, animal technicians and scientists.

PMID- 9175009
TI  - Observations on the prevalence of nest-building in non-breeding TO strain mice
      and their use of two nesting materials.
AB  - The spontaneous performance of nest-building behaviour by non-breeding laboratory
      mice suggests that routinely providing nesting material might be a suitable
      environmental enrichment. If nesting material is to be provided routinely, this
      should have characteristics which are preferred, or at least accepted by a
      considerable proportion of the animal population; it should also be inexpensive.
      The present study therefore examined the prevalence of nest-building behaviour in
      39 individually-housed, non-breeding, female mice, and their preferences for a
      commercial nesting product and a less expensive source of material (paper
      towels). Within minutes of the materials being placed in the cages, the mice
      began manipulating the paper towels. Thirty-six of the mice subsequently
      constructed nests during the first dark phase after the materials had been placed
      in the cage--the remaining three mice constructed nests during the following 48
      h. The nests were usually constructed from a mixture of the two materials, though
      observations indicated the mice might have preferred characteristics of the
      inexpensive paper towels. There was a strong tendency to build nests in the same
      location used for sleeping prior to the nesting material being provided, and
      similarly, the mice were conservative in the site chosen to build a second nest
      after the first was removed. The most frequently chosen site for nest-building
      was under the feeder. Other studies have reported a high motivation for nest
      building behaviour, widespread performance amongst many strains, and nest
      building as a thermoregulatory behaviour by animals housed in standard laboratory
      air temperature. In conjunction with these findings, the present results suggest
      that routinely providing paper towels is an inexpensive and practical means of
      environmental enrichment for non-breeding, laboratory mice.

PMID- 9175010
TI  - Preferences for nesting material as environmental enrichment for laboratory mice.
AB  - Behavioural and psychological needs of laboratory animals generally cannot
      adequately be met in standard laboratory cages. Environmental enrichment, which
      provides a more structured environment can enhance the well-being of laboratory
      animals. They may perform more of their species-specific behaviour and may
      control their environment in a better way. An easily applicable form of
      enrichment for laboratory mice is nesting material. Six different types of
      nesting materials were evaluated in a preference test with male and female
      animals of two strains [C57BL/6J or BALB/c, n = 48]. No significant differences
      in preference were found between the strains or between the sexes. All mice
      showed a clear preference for cages with tissues or towels as compared to paper
      strips or no nesting material, and for cages with cotton string or wood-wool as
      compared to wood shavings or no nesting material. Paper-derived materials were
      preferred over wood-derived materials, although the results also suggest that the
      nature (paper or wood) of the nesting material is less important than its
      structure, which determines the nestability of the material. Nesting material may
      be a relatively simple method to contribute to the well-being of laboratory mice.

PMID- 9175011
TI  - Effects of isoflurane versus halothane on myocardial contractility in rabbits:
      assessment with transthoracic two-dimensional echocardiography.
AB  - The effects of isoflurane versus halothane on cardiac contractility were
      evaluated by two-dimensional (2D) transthoracic echocardiography in rabbits. The
      relationship between the left ventricular end-systolic wall stress (LVESWS) and
      the velocity of heart rate corrected circumferential fibre shortening (Vcfc) was
      used. Arterial blood pressure, heart rate, left ventricular pressure and
      transthoracic 2D echocardiogrphic data were determined at 1 MAC (minimum alveolar
      concentration) of halothane or isoflurane, both with 50% nitrous oxide. Drug
      induced changes in pre- and afterload were performed in all study animals to
      assess the left ventricular contractile response over a wide range. LVESWS and
      Vcfc were calculated on videotape recorded M-mode tracings. Mean heart rate and
      arterial blood pressure were not significantly different between the two groups.
      Myocardial contractility under isoflurane/nitrous oxide anaesthesia was
      significantly higher than under halothane/nitrous oxide anaesthesia at 1 MAC. The
      results of the present study confirm data obtained from humans and other animal
      species and suggest that, in rabbits, myocardial contractility is best preserved
      by inhalation of isoflurane. Isoflurane should therefore be preferred over
      halothane, especially in cases of prolonged anaesthetic procedures.

PMID- 9175012
TI  - A method for long duration anaesthesia for a new hindlimb ischaemia-reperfusion
      model in mice.
AB  - To study the relationship between ischaemia-reperfusion and multiple organ
      dysfunction syndrome (MODS), a new anaesthesia method was required to be applied
      to C57BL/6 mice. These mice are also used in a well accepted, standardized model
      for MODS using intraperitoneally administered zymosan (zymosan induced general
      inflammation, ZIGI). The aim was to develop a new model for ischaemia-reperfusion
      with 6 h of anaesthesia. This and further specific requirements for the
      combination of ischaemia-reperfusion and the ZIGI method, made us select
      inhalational anaesthesia using isoflurane in oxygen. This study evaluates whether
      long-term anaesthesia confounds the results of ischaemia-reperfusion and the ZIGI
      model. In addition the benefits of using the analgesic buprenorphine were
      evaluated. Ischaemia was induced with a tourniquet around the hindlimb. Ischaemia
      and reperfusion were verified by imaging a radioactive tracer with a gamma
      camera. It was established that anaesthesia with isoflurane in oxygen caused
      little perturbation of body temperature and respiratory rate. A survival rate of
      89% without noteworthy influence on organs was obtained. Buprenorphine proved to
      provide adequate analgesia and had no influence on measured parameters. In our
      experimental setting, this model with long duration anaesthesia allowed us to
      induce ischaemia and reperfusion of the hindlimb without perturbation of
      measurements. It also allowed good exposure of the abdomen and facilitated
      combination with the ZIGI model.

PMID- 9175013
TI  - An illustrated guide to endotracheal intubation in small non-human primates.
AB  - Endotracheal intubation allows precise delivery of inhaled anaesthetic agents.
      Intubation in small non-human primates (less than 1 kg), is straightforward,
      using commercially available equipment, and careful positioning of the animal.
      Equipment and methods are fully described and illustrated.

PMID- 9175014
TI  - SCID-bg mice as xenograft recipients.
AB  - SCID-bg (scid/scid, beige/beige) is a strain of double-mutant mice with impaired
      lymphoid development and reduced natural killer (NK) cell activity. The present
      study was undertaken to evaluate the usefulness of SCID-bg mice as xenograft
      recipients. Fetal guinea pig tissues (liver, thymus, spleen) were transplanted
      under the kidney capsule of the mice and their serum guinea pig IgG levels were
      measured weekly thereafter, C.B.-17-scid and anti-asialo GM1 antiserum-treated
      (NK-depleted) C.B.-17-scid (C.B.-17-scid-AGM1) mice that received the identical
      transplants were used as controls. Throughout the experimental period (1, 2, and
      3 weeks after transplantation), the average serum guinea pig IgG concentrations
      was highest in C.B.-17-scid-AGM1 mice followed by SCID-bg mice and lowest in C.B.
      17-scid mice without antiserum treatment, though we could not find any
      statistical significance among these groups. However, SCID-bg mice always showed
      the smallest within-group variance (individual difference) in the serum guinea
      pig IgG concentrations (P < 0.05, versus C.B.-17-scid-AGM1 mice at 1, 2, and 3
      weeks and versus C.B.-17-scid mice at 2 weeks). The graft size was not
      significantly different among these three groups, but the spleen grafts in C.B.
      17-scid mice contained fewer nucleate cells than the other two groups. These
      results indicate that the reduced NK cell activity by beige mutation is not
      crucial for the success of xenogenic transplantation, though SCID-bg mice may be
      useful as xenograft recipients with a consistent potential to retain the
      viability and function of engrafted tissues.

PMID- 9175015
TI  - Practical role of genetic profiling and preservation stock of human tumour
      xenograft lines as a tool in animal experiments for antitumour drug evaluation.
AB  - Human tumour xenografts (HTXs) are a useful tool for animal experiments
      especially for evaluation of new antitumour drugs. We have been establishing
      HTXs, and have developed tumour chemosensitivity panels for new drug evaluation
      using them. With regard to quality control (problems in changes into mouse-type
      tumours and/or artificial cross-contamination among tumour lines), we studied
      genetic profiling, and effects of long-term passaging on tumour properties such
      as growth and chemosensitivities, and we discuss the use of cryopreservation
      stock of HTXs and periodic replacement in order to maintain reproducibility of
      the experimental results. We examined isozyme markers and DNA fingerprinting to
      identify species and individuality of the tumours, respectively. Growth curves
      and sensitivities to antitumour drugs were examined using HTXs with different
      passaging in nude mice. Among the tumours we maintained, five human tumours were
      found to have changed to mouse origin from their isozyme markers and were
      excluded. We identified the individuality of tumours which we used for the
      chemosensitivity panels by DNA fingerprinting, and their properties were stable
      for long-term passaging in nude mice. However, growth speed and
      chemosensitivities to drugs were altered with long-term passaging, although DNA
      fingerprint analysis did not show any obvious changes with passaging. Genetic
      profiling, such as isozyme markers and DNA fingerprinting, is useful to identify
      individuality of experimental HTXs, and tumours should be renewed periodically
      even when there are no signs of artificial contamination when they are used in
      experiments which require continuous reproducibility of experimental results.

PMID- 9175016
TI  - Ophthalmologic examination in systemic toxicity studies: an overview.
AB  - The procedures of ophthalmologic examination used by the authors during systemic
      toxicity studies in laboratory animals are presented in this paper. The present
      international guidelines with respect to the requirements for ophthalmological
      examination are given in an overview. A list of proposed keywords is included
      which may be used in describing ocular changes.

PMID- 9175017
TI  - Effective streptokinase treatment of blocked catheters in pigs and sheep.
AB  - Sheep and pigs with chronic silastic catheters with a partial blockage of the
      catheter were treated locally with streptokinase. After one week of treatment all
      affected catheters were patent again for many weeks. In sheep it proved necessary
      to use the enzyme treatment as a maintenance tool by contrast with pigs. This
      treatment may reduce the number of animals used in long-term trials requiring
      vascular access.

PMID- 9175018
TI  - Why do patients with antiphospholipid antibody clot?

PMID- 9175019
TI  - Clinico-pathological conference. Lepromatous leprosy.

PMID- 9175020
TI  - Effect of beta 2glycoprotein I and human monoclonal anticardiolipin antibody on
      the protein S/C4b-binding protein system.
AB  - The effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal
      anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system
      was evaluated. The binding of C4BP to protein S was assessed by ELISA in the
      presence of beta 2GPI with/without human monoclonal aCL. beta 2GPI downregulated
      the binding between S and C4BP significantly. Human monoclonal aCL abolished the
      beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate
      experiments, the reactivity of aCL towards protein S in the presence or absence
      of beta 2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S
      only in the presence of a combination of beta 2GPI and cardiolipin. This binding
      was Ca++ dependent. These findings suggest that human monoclonal aCL increases
      the affinity of C4BP for protein S, and that protein S may represent one of the
      targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may
      explain acquired free protein S deficiency and the attendant risk of thrombosis
      in patients with aCL.

PMID- 9175021
TI  - Enhanced expression of nucleobindin in lymphatic organs of lupus-prone mice.
AB  - Nucleobindin (Nuc) was originally identified as a 55 kDa protein that enhanced
      anti-DNA antibody production in cultures of autoimmune MRL/lpr mouse spleen
      cells. cDNA cloning and the production of recombinant protein (rNuc) have
      revealed that rNuc binds to DNA and Ca2+ by means of leucine zipper and EF-hand
      motif structures. In vitro and in vivo effects of rNuc to induce autoantibodies
      including anti-dsDNA antibody in normal mice have been demonstrated; however,
      whether Nuc is involved in the state of autoimmunity occurred in MRL/lpr, C3H/gld
      and male BXSB mice has not been elucidated. Here we report that the expression of
      Nuc mRNA is upregulated with age in the lymphatic organs and is positively
      correlated to the serum levels of Nuc in these lupus-prone strains of mice. Upon
      immunization with KLH in Freund's complete adjuvant, normal BALB/c mice also
      showed an elevated level of Nuc in their serum and elevated Nuc mRNA in their
      lymphatic organs. In addition, in vitro stimulation of BALB/c splenocytes with
      Con A or LPS remarkably enhanced Nuc mRNA expression. These results suggest that
      upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is
      related to spontaneous activation of immunocompetent cells; the present data are
      also consistent with our previous hypothesis on the role of Nuc in the induction
      or enhancement of autoimmunity in lupus models of mice.

PMID- 9175022
TI  - Predictors of renal outcome in diffuse proliferative glomerulonephritis in
      systemic lupus erythematosus.
AB  - The occurrence of nephritis is considered to be the most important factor
      influencing the prognosis in systemic lupus erythematosus (SLE). Despite the
      apparent histological similarity of the lesions, however, patients with diffuse
      proliferative glomerulonephritis (DPGN) may exhibit different outcomes. A
      retrospective study was carried out on 81 SLE patients with DPGN to evaluate the
      prognostic significance of different clinical, serological and histological
      variables; in particular, 95 renal biopsies were re-evaluated and the activity
      and chronicity indices for the patients were determined. A positive correlation
      was observed between the presence of chronic lesions on renal biopsy and a poor
      renal outcome (< 0.001). Moreover, in the repeat biopsies the patients with a
      poor outcome showed a higher degree of chronic lesions. Active lesions and other
      clinical and serological parameters did not correlate with the outcome.

PMID- 9175023
TI  - Correlation between CD29 density on CD8+ lymphocytes and serum IgG in systemic
      lupus erythematosus.
AB  - The purpose of this paper is to establish whether there is increased lymphocyte
      adhesion molecule density in systemic lupus erythematosus (SLE), which could
      alter the migration pathways and activation thresholds of lymphocytes and thus
      contribute to the pathogenesis of the disease. We analysed the CD11a, CD29 and
      CD2 bound antibody molecule (bam) density on the CD4+ and CD8+ CAMhigh (primed)
      lymphocytes of 28 SLE patients (8 active and 20 inactive by BILAG), using
      reproducible flow cytometric measurements, standardized with fluorescent beads
      and antibodies of known fluorescein: protein ratios. In a second patient cohort
      (17 patients), we investigated whether CD29 density on CD8+ cells correlated with
      measures of humoral (serum IgG) or cellular (urine neopterin) activation. In the
      first cohort, 36% of patients had elevated CD29 (beta 1 integrin) density on CD8+
      cells. In the second cohort, CD29 density on CD8+ cells was found to be closely
      associated with total plasma IgG (r = 0.71, P = 0.001), but not with urine
      neopterin, disease activity (BILAG) or drug treatment. We conclude that CD29 on
      CD8+ cells is associated with B cell activation in SLE.

PMID- 9175024
TI  - Methotrexate use in systemic lupus erythematosus.
AB  - Low dose pulse oral methotrexate (MTX) is a well established treatment for
      rheumatoid arthritis, and short term open studies have suggested beneficial
      effects of MTX in SLE. This study was designed to investigate MTX treatment
      maintenance rates in SLE using life table analysis, and to determine whether MTX
      use was associated with a dose reduction of concomitant steroid therapy. All SLE
      patients managed by physicians affiliated with a single centre were studied cross
      sectionally. Information regarding disease variables and drug use were
      ascertained by interview and chart review. Drug therapy data including dates of
      treatment and indications for treatment were analysed using Kaplan-Keier life
      table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were
      observed in 24 subjects. The period studied totalled 19766 patient-days, with a
      median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The
      median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15)
      mg/week respectively. The principal indication for commencing methotrexate
      therapy was arthritis. Only two subjects terminated treatment for toxicity, with
      the most common reason for termination being remission. The cumulative
      probability of continuing treatment was 68% at 12 months and 61% at 24 months, or
      75% and 71% respectively if cessations for remission were excluded. The median
      (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4
      492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9
      531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of
      36% of subjects reduced their steroid dose during MTX therapy, but this reduction
      was not significant. Treatment of SLE with MTX, predominantly for arthritis, was
      well tolerated over prolonged periods of observation. Toxicity of sufficient
      severity to lead to treatment termination was uncommon. A subset of subjects were
      able to reduce steroid intake during MTX therapy, but no overall reduction in
      steroid dose was observed.

PMID- 9175025
TI  - IgA deficiency and SLE: prevalence in a clinic population and a review of the
      literature.
AB  - An association between systemic lupus erythematosus (SLE) and immunoglobulin A
      (IgA) deficiency has been reported previously and may have therapeutic
      consequences for patients who require treatment with intravenous immunoglobulin.
      We report the prevalence of IgA deficiency in a clinic population of 96 patients
      with SLE. Five patients were found to be consistently IgA deficient. These
      patients were more likely to be West Indian, to have anti-Sm and anti-La
      antibodies and to have a speckled pattern of antinuclear antibody. There were no
      significant differences in clinical features between IgA deficient and other SLE
      patients, nor in SLE-related HLA alleles. We thus confirm the increased
      prevalence of IgA deficiency in patients with SLE. A review of the literature is
      presented and we speculate on the nature of the link between IgA deficiency and
      SLE.

PMID- 9175026
TI  - Immunologically restricted and inhibitory anti-Ro/SSA in monozygotic twins.
AB  - A pair of monozygotic twins with Sjogren's syndrome are described who both have
      large amounts of anti-Ro/SSA in their sera by ELISA, but no precipitin in double
      immunodiffusion. Unique among previously encountered specimens, sera from the
      twins inhibit the formation of Ro/SSA-precipitins in double immunodiffusion by
      known anti-Ro/SSA positive SLE patients. The twins have near identical, clonally
      restricted anti-Ro/SSA autoantibodies as evaluated by isoelectric focusing and
      bind the same 60 kD Ro/SSA peptides. Thus, this pair of monozygotic twins has an
      identical fine specificity in their immune response to 60 kD Ro/SSA, despite
      potential differences in their immune response generated by random processes in
      the formation of immunoglobulin molecules and T cell receptors. These data imply
      that the anti-Ro/SSA found in these sera binds less than three epitopes such that
      soluble antigen/antibody complexes are formed instead of an insoluble complex
      that precipitates.

PMID- 9175027
TI  - The prevalence of systemic lupus erythematosus in Northern Ireland.
AB  - Using six sources of patient ascertainment, 467 patients were initially
      identified as having a diagnosis of systemic lupus erythematosus (SLE) in
      Northern Ireland. The diagnosis was subsequently altered in 45 of these, either
      by the patient, their family, or their physician. The corrected source data were
      then reanalysed by the 'capture-recapture' technique, which suggested a further
      71 patients missed during the initial identification process. Eighty-eight
      patients underwent physical examination, and 14 were found to have a diagnosis
      other than SLE. A final estimated figure of 415 patients was obtained, giving a
      point prevalence on August 1, 1993 of 25.4 per 10,000 for the Province (95%
      confidence interval 22.1-28.7 per 100,000).

PMID- 9175028
TI  - Mycotic aneurysm of a coronary artery in SLE--a rare complication of salmonella
      infection.
AB  - We describe a 27y old female systemic lupus erythematosus (SLE) patient with
      salmonella bacteraemia who presented with fever, back pain and an enlarging heart
      size. A two dimensional echocardiogram (2D Echo) showed a mass in the right
      atrium. Subsequent computer tomographic (CT) and magnetic resonance imaging (MRI)
      studies showed that this had become a ring shaped lesion at the posterior end of
      the interventricular septum with an area communicating with the right atrial
      cavity. At operation a ruptured mycotic aneurysm of the right coronary artery was
      found. This is the first report of an SLE patient with a coronary artery mycotic
      aneurysm due to salmonella and the first reported case of survival following
      rupture of such aneurysm.

PMID- 9175029
TI  - Successful treatment of early secondary myelofibrosis in SLE with IVIG.
AB  - Myelofibrosis has been reported as a rare cause of pancytopenia in patients with
      autoimmune diseases. We describe a 54y old female patient who was admitted with
      severe anemia subsequently found to be due to marrow fibrosis. During the course
      of her hospitalization, relying both on her clinical symptoms as well as the
      results of a wide range of laboratory tests and diagnostic procedures, the
      diagnosis of systemic lupus erythematosus was established. The patient was
      treated with high dose steroids, but improvement of her clinical symptoms as well
      as normalization of her peripheral blood count were achieved only after high dose
      intravenous therapy with gamma globulin (IVIG) was instituted. Along with the
      improvement in the peripheral blood parameters normalization of the bone marrow
      architecture was recorded on a repeated bone marrow biopsy. IVIG therapy should
      be considered in extreme cases of bone marrow suppression in SLE.

PMID- 9175030
TI  - Shrinking lungs syndrome in systemic lupus erythematosus: improvement with
      inhaled beta-agonist therapy.
AB  - The pathogenesis and therapy of shrinking lungs syndrome in patients with
      systemic lupus erythematosus remains controversial. It has been previously
      reported that corticosteroid treatment can be effective. We report a patient with
      shrinking lungs syndrome who presented a good response to inhaled beta-agonist
      therapy. Therapeutic approach to this syndrome is discussed.

PMID- 9175031
TI  - Intravenous immunoglobulin therapy is not able to efficiently control cutaneous
      manifestations in patients with lupus erythematosus.

PMID- 9175032
TI  - The thyroid. Fine-needle biopsy and cytological diagnosis of thyroid lesions.

PMID- 9175033
TI  - HLA-derived peptides as novel immunosuppressives.
AB  - Over the past decade the use of synthetic peptides corresponding to linear
      sequences of HLA molecules has progressed from a concept to a reality. These
      peptides are currently being evaluated in clinical trials. In animal models these
      peptides, given over 1 week with cyclosporin alone, induced long-term
      immunological tolerance (Figure 3). They may similarly induce tolerance in
      humans. The next major hurdle for such tolerogenic drugs, however, is to prove
      efficacy in clinical circumstances. Many of the drugs used to treat transplant
      patients today (steroids, cyclosporin, azathioprine, mycophenolate mofetil) may
      actually inhibit the 'active' processes of induction and maintenance of
      immunological tolerance. Demonstration that new drugs induce tolerance will
      require efficacy studies in other immune-mediated diseases in which monotherapy
      is feasible (such as psoriasis), before further advances can be made in the
      induction of transplant tolerance. In addition, rapid assays of rejection must be
      developed in order to reverse tolerance induction failures without graft damage
      or loss. Lastly, it will require heroic physicians, surgeons, and patients to
      make immunological tolerance a reproducible clinical reality.

PMID- 9175034
TI  - Blood pressure measurement and standards in children.

PMID- 9175035
TI  - Intradialytic renal haemodynamics--potential consequences for the management of
      the patient with acute renal failure.

PMID- 9175036
TI  - Renal replacement therapy in the elderly: an old problem with young solutions.

PMID- 9175037
TI  - Vascular access thrombosis--what are the possibilities of intervention?

PMID- 9175038
TI  - The management of iron metabolism in recombinant human erythropoietin treated
      dialysis patients by Dutch nephrologists.
AB  - BACKGROUND: The regulation of iron metabolism is an important aspect of r-HuEPO
      treatment. METHOD: All Dutch nephrologists involved in dialysis were asked to
      complete a questionnaire about iron metabolism management in dialysis patients.
      RESULTS: The response rate was 68%, covering 83% of all Dutch dialysis units.
      Iron status is assessed before starting r-HuEPO by 96% of the respondents, but
      only 58% waits for the results. Serum ferritin is determined by 98%, MCV by 77%,
      transferrin saturation by 44%, the percentage hypochromic red blood cells by 6%,
      bone marrow iron staining by 4%, and serum transferrin receptors by 0%. Serum
      ferritin is considered to be the most important parameter by 48%, transferrin
      saturation by 37%, percentage hypochromic red blood cells and serum transferrin
      receptors by 0%. Of the respondents, 17% determines iron status twice a year, 13%
      three times, 54% four times, 4% six times, 4% eight times, and 8% twelve times.
      Iron is given to all patients by 40% of the nephrologists, 60% prescribes iron on
      indication. Oral substitution is preferred by 90%, but 27% incidentally
      prescribes intravenous iron without testing the effects of oral iron. Of all
      haemodialysis patients on r-HuEPO, 16% (SD 18, median 10) receives no iron
      substitution, 65% (+/- 28, 73) oral iron and 19% (+/- 28, 6) intravenous iron. Of
      all CAPD patients, 22% (+/- 24, 16) receives no iron substitution, 77% (+/- 24,
      81) oral iron, and 1% (+/- 2, 0) intravenous iron. CONCLUSION: There is no
      communis opinio among Dutch nephrologists on the frequency of iron status
      assessment, the choice of parameters, the indications for iron substitution, or
      the decision between oral or intravenous substitution.

PMID- 9175039
TI  - Survival in long-term haemodialysis patients: results from the annual survey of
      the Japanese Society for Dialysis Therapy.
AB  - The prognosis for haemodialysis patients is reported to be more favourable in
      Japan than in Europe or North America. Consequently, evaluation of the death
      predictors for haemodialysis patients in Japan is of considerable interest
      outside Japan. The Patient Registration Committee of the Japanese Society for
      Dialysis Therapy annually surveys the individual patient case mix, laboratory
      data and important events occurring in the previous years. Thus, using case mix
      data and laboratory data (including Kt/V and protein catabolic rate) from the
      1993 questionnaire survey and the individual patients' life/death statistics from
      the 1994 questionnaire survey, a logistic regression analysis was conducted on
      53867 patients. The analysis indicated that important death risk predictors were:
      (i) advanced age, (ii) occurrence of diabetes mellitus, (iii) male sex, (iv) Kt/V
      lower than 1.8, (v) haemodialysis time less than 5 h, (vi) protein catabolic rate
      less than 0.9 g/kg/day, and (vii) percentage body weight decrease less than 4%
      and more than 8% during the first haemodialysis session of the week.

PMID- 9175040
TI  - Current status of renal replacement therapy in Japan: results of the annual
      survey of the Japanese Society for Dialysis Therapy.
AB  - Beginning in 1966, the Patient Registration Committee of the Japanese Society for
      Dialysis Therapy has conducted a survey once a year on renal replacement therapy
      in Japan. As of 1983, the survey covered the life/death of patients in the survey
      years, as well as the case mix of individual patients. In 1990 several laboratory
      variables were added to the survey items. The present report summarizes the data
      from the 1993 and 1994 surveys. The Committee mailed out questionnaire forms at
      the end of the survey year to the heads of all dialysis facilities. Survey forms
      were returned from 99.6% of the dialysis facilities in the 1993 survey, and from
      99.8% of the facilities in the 1994 survey. Some 143709 patients were treated by
      renal replacement therapy in 1994 (7509 were treated by CAPD, and 131016 by
      extracorporeal haemopurification). The gross mortality rate was 9.5% in the same
      year. The mean values of the laboratory variables among 88693 patients undergoing
      thrice weekly haemodialysis were as follows in 1993: Kt/V, 1.31 +/- 0.30; protein
      catabolic rate, 1.04 +/- 0.30 g/kg/day; haemodialysis time, 4.12 +/- 0.50 h. In
      1994, the variables were: predialysis serum creatinine concentration, 11.54 +/-
      2.85 mg/dl; predialysis serum albumin concentration, 3.91 +/- 0.55 g/dl;
      predialysis haematocrit, 28.69 +/- 4.36%.

PMID- 9175041
TI  - Leukocyte infiltration and ICAM-1 expression in two-kidney one-clip hypertension.
AB  - How an increase in blood pressure, in and of itself, induces hypertensive
      nephrosclerosis is unclear. In an earlier study we found that leukocyte
      infiltration, proximal tubular cell proliferation, matrix deposition and
      interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt
      hypertensive rats. In this study we tested the hypothesis that the cell surface
      adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular
      epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined
      the clipped kidney as well. We found that systolic blood pressure was
      significantly elevated in renovascular hypertensive rats compared to sham
      operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001).
      Furthermore, quantitative (densitometry) measurements showed that ICAM-1
      expression on vascular endothelium and on tubular cells was significantly
      increased in unclipped kidneys compared to controls (P < 0.05). The same was true
      for monocyte and granulocyte infiltration (P < 0.05). These same variables were
      even more prominent in the clipped kidneys, compared to unclipped and control
      kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys
      exposed to hypertension as well as in clipped kidneys exposed to ischemia. We
      suggest that mechanical injury induced by increased blood pressure is responsible
      for an inflammatory adhesion molecule-mediated response and concomitant renal
      injury.

PMID- 9175042
TI  - Myofibroblast phenotypes expression in experimental renal scarring.
AB  - BACKGROUND: Myofibroblasts have been implicated in the pathogenesis of wound
      healing and tissue fibrosis. A role has also been put forward for these cells in
      the development of experimental and clinical renal scarring. SUBJECTS AND
      METHODS: We examined the expression of myofibroblast phenotypes by
      immunohistochemistry, relying on an avidin-biotin-peroxidase method, during the
      course of renal scarring in rats submitted to subtotal (5/6) nephrectomy (SNx).
      We also attempted to identify changes in immunoreactive transforming growth
      factor-beta (TGF-beta) and collagen (III and IV) within remnant kidneys in order
      to determine their association with the expression of the myofibroblasts.
      RESULTS: In normal sham-operated rats, alpha-smooth muscle actin (alpha-SMA) was
      confined to the media of renal arteries and arterioles. In contrast, in rats with
      renal ablation we observed the early (day 7) appearance of myofibroblasts
      expressing alpha-SMA (A) in the interstitium of remnant kidneys particularly
      around vessels. Interstitial cells expressing alpha-SMA increased with time as
      tubulointerstitial fibrosis progressed. By day 30 some interstitial cells also
      expressed vimentin (V). Various interstitial myofibroblast phenotypes (A, V, VA)
      were expressed during the course of experimental renal scarring. Interstitial
      myofibroblasts appeared to be associated with TGF-beta as these cells' cytoplasm
      stained for both this growth factor and alpha-SMA. Interstitial fibrosis was also
      associated with increased interstitial expression of both collagen III and IV.
      Some atrophic tubular cells showed positive immunostaining for vimentin during
      the late stages of renal scarring (days 90-150). In the glomeruli, a segmental
      expression of alpha-SMA was noted from day 21 after SNx onward. Normal glomerular
      endothelial cells appeared to express vimentin while epithelial cells expressed
      both vimentin and desmin (D). The glomerular immunostain for vimentin increased
      with time but decreased as glomerulosclerosis progressed. In contrast, glomerular
      desmin and alpha-SMA immunostain continued to rise with progressive
      glomerulosclerosis. This was associated with the appearance of type III collagen
      within scarred glomeruli. Both vimentin and desmin appeared within the walls of
      the renal arterioles and increased with time from day 7 and 15, respectively.
      Vimentin was also expressed in the peritubular capillaries of remnant kidneys. By
      contrast, alpha-SMA, normally present in the media of arterioles, decreased as
      arteriolar sclerosis progressed. These changes cannot be exclusively attributed
      to systemic hypertension as they were absent in a group of age-matched, sham
      operated, spontaneously hypertensive rats. DISCUSSION: Myofibroblasts may play a
      role in the pathogenesis of glomerulosclerosis, tubulointerstitial fibrosis and
      vascular sclerosis. Further, the acquisition of new myofibroblastic phenotypes by
      glomerular and tubular cells may contribute to renal fibrosis.

PMID- 9175043
TI  - Human renal tubular epithelial cells as target cells for antibodies to proteinase
      3 (c-ANCA).

PMID- 9175044
TI  - Lipid and apolipoprotein patterns during erythropoietin therapy: roles of
      erythropoietin, route of administration, and diet.
AB  - BACKGROUND: Long-term effects of rHuEpo on the blood lipid profile have not been
      well documented. The aim of this paper is to prospectively evaluate whether
      rHuEpo therapy affects lipid metabolism, and whether these effects are influenced
      by changes in dietary habits and by route of rHuEpo administration. METHODS: The
      study was performed in 33 maintenance haemodialysis patients (MHP) treated for
      one year with rHuEpo either intravenously (n = 15) or subcutaneously (n = 18),
      three times per week at the end of each dialysis session. The doses were 50 IU/kg
      intravenously or 35 IU/kg subcutaneously during the first 6 months and 20 IU/kg
      during the following months. The control group consisted of 17 MHP not treated
      with rHuEpo. Total cholesterol, LDL-cholesterol and HDL-cholesterol,
      triglycerides, apolipoproteins Al and B, haemoglobin, serum albumin, blood urea
      nitrogen, serum creatinine, Kt/V, protein catabolic rate, and plasma
      erythropoietin were assessed at months 0, 2, 4, 6, 9, 12 and 2 weeks after rHuEpo
      discontinuation. Changes in food intake were evaluated on the basis of weekly
      dietary diaries before, and 3 and 9 months after treatment. Patients were divided
      into two groups: group A consisted of 19 patients who showed an increase in their
      energy intake (10% or more of basal value), and group B was formed by 14 patients
      without or with slight changes in their food intake. After the 6th month,
      dialysis schedules were adapted to new protein catabolic rate values in patients
      who increased their food intake. RESULTS: During follow-up, there were no
      significant changes in any of the parameters in the control group. In group A,
      blood urea nitrogen, serum creatinine, protein catabolic rate, cholesterol, LDL
      cholesterol, triglycerides and apolipoprotein B increased significantly since the
      first months of rHuEpo treatment, and changes in cholesterol and apolipoprotein B
      correlated significantly with changes in protein catabolic rate. In group B,
      cholesterol, LDL cholesterol, and apolipoprotein B decreased significantly after
      the 6th month of treatment, without changes in blood urea nitrogen, serum
      creatinine and protein catabolic rate values. In both groups A and B, HDL
      cholesterol decreased significantly until the 6th month and returned to basal
      values in the following months and apolipoprotein Al decreased until the 4th
      month and rose to levels higher than basal values in the following months. First
      rHuEpo administration and rHuEpo suspension at end of follow-up did not show any
      acute effect on lipid profile, despite significant changes in plasma
      erythropoietin values. Changes in lipid profile were similar with intravenous and
      subcutaneous administration of rHuEpo. CONCLUSIONS: We infer that long-term
      rHuEpo treatment positively affects the lipid profile, but in some patients who
      show exaggerated increase in their food intake these effects may be balanced and
      overcome by increment in some atherogenic blood lipid fractions. The changes in
      lipid and apolipoprotein patterns during rHuEpo therapy are not influenced by
      route of rHuEpo administration.

PMID- 9175046
TI  - Autonomic nervous system and adrenergic receptors in chronic hypotensive
      haemodialysis patients.
AB  - BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not
      elucidated. The possible role of autonomic nervous system dysfunction and
      adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in
      this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17
      normotensive HD patients, and 17 control subjects were studied. We evaluated the
      integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic
      efferent pathway ('deep-breathing test') and the sympathetic efferent pathway
      ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and
      lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2
      adrenoceptor response (intracellular cAMP generation after isoproterenol
      stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the
      deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio
      was lower in hypotensive patients than in normotensive patients (P < 0.01),
      whereas the pressor response to the hand-grip test was reduced only in
      hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood
      pressure (MBP) correlated with MBP increases during the hand-grip exercise (r =
      0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of
      patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD
      patients than in normotensive patients (P < 0.05). alpha 2- and beta 2
      adrenoceptor densities and beta 2-adrenoceptor response were reduced in
      hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with
      alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P <
      0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients
      have increased plasma catecholamine levels with preserved alpha 2- and beta 2
      adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive
      patients, plasma adrenaline levels were even higher; the increased plasma
      catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation.
      This downregulation may play a role in the reduced cardiovascular responses to
      adrenergic stimuli reported in hypotensive HD patients.

PMID- 9175045
TI  - Subacute infusion of physiological doses of parathyroid hormone raises blood
      pressure in humans.
AB  - BACKGROUND: Acute administration of parathyroid hormone (PTH) causes vasodilation
      and blood pressure decrease in experimental animals. This effect contrasts with
      the putative role of secondary hyperparathyroidism in the pathogenesis of
      hypertension of patients with renal failure. Uraemia is characterized by insulin
      resistance and hyperinsulinaemia. We therefore investigated whether subacute
      administration of physiological doses of human 1,34-PTH affects blood pressure
      under conditions of controlled insulin levels (euglycaemic clamp technique) in
      humans. METHODS: In a double-blind cross-over design 10 healthy male subjects
      received, on two occasions, in random order, for 2 h, either a sham infusion or
      an infusion of 200 units of 1,34-PTH. RESULTS: Mean ionized calcium concentration
      increased significantly (P < 0.01) within the normal range during euglycaemic
      hyperinsulinaemia, both with sham infusion (from 1.25 +/- 0.04 to 1.29 +/- 0.02
      mmol/l) and with infusion of 1,34-PTH, but the increase was more marked with 1,34
      PTH administration (from 1.26 +/- 0.05 to 1.33 +/- 0.07). In addition, mean
      platelet intracellular calcium concentration (by fluorescence spectroscopy) was
      unchanged with sham infusion (49.9 +/- 4.1 versus 50.3 +/- 5.0 nmol), but
      increased significantly (P < 0.05; paired t-test) after 1,34-PTH infusion (from
      49.8 +/- 5.0 to 52.8 +/- 5.8). The infusion of 1,34-PTH resulted in a significant
      (P < 0.01) increase in mean MAP (from 84 +/- 5 to 88 +/- 5 mmHg) as compared with
      sham infusion (85 +/- 4 versus 86 +/- 4). The intra-individual changes in
      intracellular calcium concentration (delta[Ca2+]i) were significantly correlated
      to the changes in mean MAP (delta MAP) (r = 0.87, P < 0.001). In contrast to
      blood pressure, insulin sensitivity was not affected by 1,34-PTH infusion (M
      value: 7.2 +/- 1.6 mg/kg per min) as compared with sham infusion (7.3 +/- 1.4).
      CONCLUSION: Subacute administration of physiological doses of parathyroid hormone
      under hyperinsulinaemic conditions significantly affects intracellular calcium
      and blood pressure in healthy subjects, but does not affect the action of
      insulin.

PMID- 9175047
TI  - ACE inhibitors captopril and enalapril induce regression of left ventricular
      hypertrophy in hypertensive patients with chronic renal failure.
AB  - BACKGROUND: Left ventricular hypertrophy is frequently noted in patients with
      moderate to severe chronic renal failure not requiring dialysis. Recently,
      several studies have shown reversal of myocardial hypertrophy in end-stage renal
      disease with long-term pharmacological control of blood pressure, but it is
      unclear whether left ventricular mass regresses or normalizes with
      antihypertensive treatment of patients with earlier stages of chronic renal
      failure. METHODS: Seventy-two undialysed patients with chronic renal failure,
      chronic mild-to-moderate hypertension, and left ventricular hypertrophy were
      randomly assigned in a prospective study to either the captopril (n = 36) or
      enalapril group (n = 36). Blood pressure measurements, echocardiographic and
      Doppler parameters were evaluated before treatment and at 6 and 12 months of
      therapy. RESULTS: During follow-up, six patients developed side-effects including
      dry cough, taste disturbances, skin rash and gastric intolerance. In the
      captopril group there was a decrease in mean left ventricular mass index by 12%
      after 6 months of treatment, which decreased by 20% after 12 months treatment.
      For enalapril, the average reduction of myocardial mass after 6 months treatment
      was 14% and after 12 months treatment, the decrease was 19%. In both treatment
      groups there was significant improvement of left ventricular filling dynamics. No
      deterioration of left ventricular systolic function was observed. CONCLUSIONS:
      Our results confirm that antihypertensive monotherapy with the ACE inhibitors,
      captopril and enalapril, in patients with chronic renal failure results in
      regression of left ventricular mass index associated with a significant
      improvement in the diastolic function of the left ventricle without a
      demonstrable deterioration in left ventricular systolic performance.

PMID- 9175048
TI  - Sudden death in chronic dialysis patients.
AB  - METHODS: Causes of sudden death were investigated in 113 chronic dialysis
      patients who died during the 10-year period from July 1979 to January 1989;
      postmortem examination was performed on 93 of the cases (autopsy rate; 82.3%).
      Sudden death was regarded as death 24 h after the onset of acute illness in
      patients without any restriction in their daily activities. There were 35 sudden
      death cases out of the 93 autopsied chronic dialysis patients. We analysed the
      causes of sudden death for all chronic dialysis patients and for those who died
      suddenly. RESULTS: The mean age of the 93 cases was 61.4 +/- 10.5 years (+/-SD).
      Stroke was the most frequent cause of death (24 cases, 25.8%) in the 93 autopsied
      cases. This was followed by cardiac disease in 18 (19.4%), infectious disease in
      16 (17.2%), malignancy in 14 (15.1%), and dissecting aortic aneurysm in 5 (5.4%).
      The mean age of the 35 sudden death cases was 60.9 +/- 10.9 years. Of the 35
      sudden death cases in chronic dialysis patients, dissecting aortic aneurysm was
      the most common cause of sudden death (5 cases, 14.3%), followed by cerebral
      haemorrhage in three (8.6%), acute subdural haematoma in three (8.6%), acute
      myocardial infarction in two (5.7%), cerebral infarction in two (5.7%), and
      subarachnoidal haemorrhage in one (2.9%). CONCLUSIONS: Dissecting aortic
      aneurysm, leading frequently to stroke as a cause of sudden death in chronic
      dialysis patients, at least in Japan, should be carefully differentiated from
      other cardiac diseases in chronic dialysis patients, such as severe
      atherosclerosis.

PMID- 9175050
TI  - Effect of RenaGel, a non-absorbable, cross-linked, polymeric phosphate binder, on
      urinary phosphorus excretion in rats.
AB  - BACKGROUND: Normalization of serum phosphorus is critical in the treatment of End
      Stage Renal Failure patients. Aluminum or calcium based phosphate binders, while
      efficacious, are associated with potential adverse side effects and toxicities.
      We have developed RenaGel, a novel, non-absorbed hydrogel which binds dietary
      phosphate leading to increased fecal excretion, decreased absorption and
      decreased serum phosphorus levels. In this paper, we present results from both in
      vitro and in vivo studies in which we examined the efficacy of this novel
      phosphate binder. METHODS: In vitro, RenaGel was suspended in the test solution,
      and the mixture was stirred for 1 hour at room temperature. The solid was then
      filtered off, and the residual liquid analyzed for phosphate. In vivo, RenaGel
      was mixed in rodent feed at different concentrations and fed to normal rats for
      up to 4 days. Urine was collected and analysed for phosphate content. RESULTS AND
      CONCLUSIONS: In vitro binding studies demonstrate that RenaGel has an extremely
      high phosphate binding capacity. At an estimated physiological concentration of 5
      mM phosphate, RenaGel binds 2.6 mmole phosphate/g of phosphate binder. The in
      vivo binding study shows that RenaGel mixed into the diet decreased urinary
      phosphorus excretion in a dose dependent manner. RenaGel particles with a 23
      microns mean diameter are more efficacious than the larger ones. In conclusion,
      the above studies indicate that RenaGel is a potent phosphate binder. RenaGel
      contains no calcium or aluminum and offers an alternative to existing phosphate
      binder treatments.

PMID- 9175049
TI  - Hepatitis G virus infection in a haemodialysis unit: prevalence and clinical
      implications.
AB  - BACKGROUND: Hepatitis viruses have become one of the main infectious problems in
      patients on long-term haemodialysis. A new RNA virus, designated hepatitis G
      virus (HGV) has been recently identified. The pathogenic relevance of this virus
      is currently under investigation. The aim of this study was to analyse the
      prevalence and clinical implications of hepatitis G virus infection in patients
      on haemodialysis. METHODS: The presence of HGV-RNA was investigated in 96
      patients on maintenance haemodialysis. Hepatitis viral markers (HBsAg, anti-HCV,
      HGV-RNA) and liver tests were assessed in all these patients, as well as the risk
      factors for hepatitis viruses acquisition. As a control group, 200 blood donors
      were tested for the presence of HGV-RNA. RESULTS: HGV-RNA was detected in 25 of
      96 patients on haemodialysis (26%) and in six of 200 blood donors (3%) (P <
      0.001). Thirteen of 25 HGV infected patients (52%) were coinfected with other
      hepatitis viruses (HBV and/or HCV). Evidences of chronic liver disease were more
      frequent in patients infected by HBV and/or HCV (61%) than in patients infected
      by HGV alone (17%) (P = 0.01). Although 80% of HGV infected patients had received
      blood products, the transfusion rate was not different from non HGV-infected
      patients. Time on haemodialysis was significantly shorter in patients infected
      with HGV alone (3.1 +/- 3.5 years) compared to patients infected with HBV and/or
      HCV (7.6 +/- 5.8 years) (P = 0.04). CONCLUSIONS: Patients on maintenance
      haemodialysis are at increased risk for HGV infection. HGV infection itself does
      not seem to be a frequent cause of chronic liver disease in these patients. Since
      the prevalence of HGV infection in blood donors is high, blood transfusion could
      be one of the main factors implicated in HGV transmission in patients on
      haemodialysis.

PMID- 9175051
TI  - A comparison of dialysers with low-flux membranes: significant differences in
      spite of many similarities.
AB  - The solute removal characteristics and haemocompatibility of low-flux dialysers
      containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and
      polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross
      over clinical trial. While all four dialysers provided comparable removal of urea
      and creatinine, the dialyser containing PMMA membrane showed a reduced ability to
      remove phosphate compared to that containing Cuprophan membrane. Significant beta
      2-microglobulin removal was obtained with the dialyser containing Gambrane
      membrane, whereas the other three dialysers had no impact on plasma beta 2
      microglobulin concentrations. The ability to activate complement, measured as
      changes in the plasma concentrations of C3a des Arg and the terminal complement
      complex, and to produce leukopenia was greater for the dialyser containing
      Cuprophan membrane than for the other three. The ability to activate complement
      and cause leukopenia was not consistent among the remaining three dialysers and
      the degree of leukopenia could not be predicted from the level of complement
      activation. Neutrophil degranulation, as indicated by the release of elastase
      alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers
      containing Cuprophan and Gambrane membranes. None of the dialysers was overtly
      thrombogenic as judged by changes in platelet count and plasma concentrations of
      the thrombin-antithrombin III complex. Our results demonstrate that although
      there are many similarities between dialysers containing low-flux membranes,
      there are also significant differences. These differences may enable improvements
      in therapy, while allowing continued use of low-flux dialysers.

PMID- 9175052
TI  - Improved cytosolic free calcium mobilization and superoxide production in
      bicarbonate-based peritoneal dialysis solution.
AB  - BACKGROUND: Intraperitoneal phagocytes play an important role in local host
      defence to prevent CAPD peritonitis. The intracellular calcium [Ca2+]i is thought
      to be involved in the regulation of various cell functions. This study therefore
      investigates the effect of lactate-based dialysis solution (LBDS) and bicarbonate
      based dialysis solution (BBDS) on cytosolic free calcium mobilization and
      superoxide production (SP) as important steps in signal transduction and
      bacterial killing. METHODS: We studied changes in [Ca2+]i and SP following
      stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) in
      polymorphonuclear neutrophils (PMNs) incubated in either LBDS-pH 5.2, LBDS
      adjusted to pH 7.4, 1:10 diluted spent and fresh LBDS or BBDS-pH 7.4 with
      different glucose concentrations, comparing the data with cells treated with
      Hanks buffer (HBSS) pH 7.4 as control. To elucidate the effect of glucose and
      lactate PMNs were additionally incubated in HBSS-pH 7.4, containing glucose (HBSS
      Glu-pH 7.4) or lactate (HBSS-Lact-pH 7.4) in the same concentrations as contained
      in CAPD solutions and tested as above. PMNs were isolated from healthy blood
      donors and incubated with dialysis solution 10 min prior to stimulation with
      fMLP. RESULTS: [Ca2+]i mobilization and SP were completely inhibited in PMNs
      incubated in LBDS pH 5.2. pH adjustment of LBDS to 7.4 and 1:10 dilution of spent
      and fresh LBDS corrected some of the suppression of the calcium influx and
      superoxide production. BBDS pH 7.4, however, preserved physiological cell
      function significantly better at low (1.5 and 2.3%) glucose concentrations.
      CONCLUSION: In comparison to conventional lactate-based dialysis solution, pH
      adjusted and 1:10 diluted LBDS, bicarbonate-based dialysis solution is more
      biocompatible since it preserves significantly better neutrophil cell functions.

PMID- 9175053
TI  - Diffusion of HCV through peritoneal membrane in HCV positive patients treated
      with continuous ambulatory peritoneal dialysis.
AB  - PURPOSE OF THE STUDY: We evaluated the presence of HCV in the peritoneal
      effluents of viraemic patients treated with continuous ambulatory peritoneal
      dialysis (CAPD) to evaluate the risk of transmitting the infection with this
      procedure. PROCEDURE: Fifteen of 81 CAPD patients (18.5%) had anti-HCV antibodies
      and eight were viraemic. At the beginning of CAPD two of the viraemic patients
      had ascites with a clinical picture of chronic active hepatitis and cirrhosis.
      Peritoneal dialysates were collected after an overnight exchange with 1.36%
      glucose and after a 4-h exchange with 3.86% glucose. Fluids from the overnight
      exchange were spun to obtain a cellular pellet and the supernatant 100-fold
      concentrated. RESULTS: No viral genome could be detected in unconcentrated
      samples and in cellular pellets, while HCV-RNA at low titre was detected in
      concentrated dialysates from the two patients with active liver disease.
      CONCLUSIONS: Our findings confirm that HCV may be present in the CAPD effluent of
      some patients; however, the titre of virus in the effluent was extremely low, at
      the limit of detection of the PCR assay. Peritoneal fluids originating from
      patients with HCV associated severe liver disease may be a potential source of
      infection.

PMID- 9175054
TI  - High serum D-lactate in patients on continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: As abnormally high serum D-lactate levels may cause neurological
      impairment, we determined whether patients undergoing continuous ambulatory
      peritoneal dialysis (CAPD) with lactate-containing fluids have increased serum D
      lactate concentrations. METHODS: D- and L-lactate concentrations were determined
      in peritoneal dialysis fluids and in serum from control subjects (n = 10),
      haemodialysis patients (n = 10), and CAPD patients (n = 30) before and after 1 h
      of dialysis. RESULTS: We found the median D-lactate concentration in Dianeal CAPD
      fluid to be 26 mM (range 19-27), whereas it was less than 0.5 mM in DPCA2 fluid.
      Control, haemodialysis, and CAPD (DPCA2) patient median serum D-lactate
      concentrations were below 0.07 mM. However, CAPD (Dianeal) patient serum D
      lactate concentrations were 4-fold higher than controls (P < 0.0001), at 0.28 mM,
      an hour after instillation of D-lactate-containing fluid. Three patients, whose
      serum D-lactate averaged 0.59 mM, were found to have D-lactate concentrations at
      0.22 mM after overnight cessation of dialysis. CONCLUSION: We conclude that CAPD
      with D-lactate-containing fluids raises serum D-lactate to abnormal levels.

PMID- 9175055
TI  - Evolution of hyperparathyroidism after renal transplantation in children--effect
      of pre-emptive transplantation and duration of dialysis.
AB  - BACKGROUND: The main causes of secondary hyperparathyroidism in end-stage renal
      disease are supposed to disappear after renal transplantation thanks to good
      graft function, but the regression of the glandular hyperfunction often takes a
      long time. The aim of the present work was to evaluate the possible role of the
      duration of dialysis in the outcome of parathyroid function after renal
      transplantation in children. METHODS AND RESULTS: The study was based on data
      from calcium-phosphate metabolism before and over a 90-day period after renal
      transplantation in 41 children. Patients were divided into: group I, pre-emptive
      transplantation (n = 17), and group II, dialysis prior to transplant (n = 24).
      Groups were matched for age, sex, causes of chronic renal failure, duration of
      ischaemia time and immunosuppressive treatment. No significant difference was
      noted with respect to all assessments of serum Ca, P, 25OHD and Mg between the
      two groups. On the other hand, PTH was statistically different both before and
      after renal transplantation, while glomerular filtration rate and tubular
      function tests were identical. CONCLUSION: It is therefore suggested that
      children submitted to pre-emptive transplantation achieve normal PTH levels
      sooner than dialysed children, which might denote an 'inappropriate PTH
      secretion' in the latter group. Skeletal resistance to PTH, low density of
      calcitriol receptor in parathyroid and/or nodular rather than diffuse hyperplasia
      of the gland could be speculated to explain such conclusions.

PMID- 9175056
TI  - Lack of evidence for natural cytotoxicity deficiency against human ex vivo tumour
      cells in allograft recipients.
AB  - BACKGROUND: Allograft recipients, who have a high risk of developing
      malignancies, are deficient in natural killer cells which mediate natural
      cytotoxicity against tumour cells. We evaluated the relevance of NK deficiency in
      transplant patients with regard to the natural lysis of human tumour cells.
      METHODS: Target cells were ex vivo tumour cells, obtained from solid tumours from
      kidney transplant patients and non-immunocompromised patients. Peripheral blood
      was extracted from kidney recipients and from normal controls. Mononuclear cells
      were separated after anti-CD3 and anti-TCR immunostaining to obtain NK and T cell
      subsets. LAK cells were obtained by in vitro IL2-activation. For each tumour,
      natural cytotoxicity assays were performed to compare effector cells from a
      kidney recipient with those from a normal control. Twenty-seven solid tumours,
      either allogenic or syngenic, were analysed, mainly consisting of renal, colon,
      and skin carcinomas. RESULTS: Natural cytotoxicity assays on K562 targets
      confirmed the expected NK deficiency in the kidney recipients. However, the NK
      and LAK cells from the kidney recipients did not kill a smaller number of tumour
      target cells than the controls, whatever the tumour type, under both the syngenic
      and allogenic conditions. CONCLUSIONS: We conclude that natural cytotoxicity
      against human tumour cells cannot be extrapolated from the cytotoxicity assays
      with established cell lines, and that natural lysis of ex vivo human tumour cells
      is not impaired in transplant patients.

PMID- 9175057
TI  - A UK-wide trial of the Banff classification of renal transplant pathology in
      routine diagnostic practice.
AB  - BACKGROUND: The Banff classification of renal transplant pathology has gained
      wide support since its introduction in 1993. There have been several studies
      which have tested its usefulness in the context of research-oriented centres. We
      sought to evaluate its use in a wider context. METHODS: We recruited pathologists
      from all but one of the renal transplant centres in the UK. Sections were
      circulated from 21 selected, 'difficult' cases, in all of which the clinical
      question was confirmation or exclusion of acute rejection, and in all of which a
      definite diagnosis had been obvious from the subsequent clinical course.
      Participants were asked first to diagnose or exclude acute rejection by their
      usual approach, then to apply the Banff classification. No clinical information
      was given beyond the time since engraftment, in order to confine the evaluation
      to the morphological features present in the sections. At the end of the study
      the subjective impressions of the participants were sought using a structured
      questionnaire. RESULTS: Using the Banff classification produced no detectable
      difference in the number of 'correct' diagnoses when compared with a conventional
      approach, irrespective of whether the 'correct' diagnosis is based on
      retrospective clinical information or on the consensus opinion of the
      pathologists involved, and irrespective of where in the Banff schema one applies
      a 'cut-off' for the diagnosis of acute rejection. However, the reproducibility of
      the diagnoses was improved. The results suggest that in the Banff classification
      the best 'cut-off' for the diagnosis of acute rejection is between Banff category
      3 and category 4, although in this difficult area we found a large improvement in
      diagnostic accuracy if input of clinical information occurs. CONCLUSIONS: The
      improved reproducibility justifies the use of the Banff classification to
      harmonise approaches between centres, especially in research projects. While
      there are good reasons also to adopt it in routine diagnostic practice, further
      refinement is necessary before an improvement in the accuracy of diagnosis can be
      demonstrated.

PMID- 9175058
TI  - Effect of a specific endothelin receptor A antagonist and an angiotensin
      converting enzyme inhibitor on glomerular mRNA levels for extracellular matrix
      components, metalloproteinases (MMP) and a tissue inhibitor of MMP in
      aminonucleoside nephrosis.
AB  - BACKGROUND: We previously reported that mRNA levels for extracellular matrix
      (ECM) components and endothelin (ET)-1 are upregulated in glomeruli of puromycin
      aminonucleoside (PAN) nephrosis. Angiotensin-converting enzyme (ACE) inhibitors
      are effective in experimental models of renal injury, including PAN nephrosis.
      This study was designed to assess whether the glomerular expression of mRNA for
      ECM components, ET-1, metalloproteinases (MMP), and a tissue inhibitor of
      metalloproteinases (TIMP) is modulated by a specific endothelin receptor A
      antagonist (FR139317) or angiotensin-converting enzyme inhibitor (enalapril) in
      PAN-injected rats. METHODS: Animals were divided into six groups. Group 1
      consisted of PAN-injected rats given no treatment. In group 2, PAN-injected rats
      were given enalapril 35 mg/l. In group 3, PAN-injected rats were given an
      intraperitoneal injection of FR139317. Group 4 consisted of saline-injected rats
      given no treatment. In group 5, saline-injected rats were given enalapril. In
      group 6, saline-injected rats were given FR139317. We prepared glomerular RNA and
      performed Northern blot analysis in all groups. RESULTS: In PAN nephrosis,
      glomerular mRNA levels for alpha 1 (IV) collagen chain, laminin B1 and B2 chains,
      ET-1, MMP-2 and TIMP-1 increased at the peak of proteinuria on day 8 and then
      decreased to the control level by day 20, whereas those for alpha 1 (I) and alpha
      1 (III) collagen chains, MMP-1, MMP-3 and GAPDH showed little change in PAN
      nephrosis throughout the experimental periods. In contrast, mRNA levels for
      heparan sulphate proteoglycan (HSPG) decreased on day 8 and then increased to the
      control level by day 20. Both enalapril and FR139317 attenuated the increases in
      mRNA levels for alpha 1 (IV) collagen chain (P < 0.01), laminin chains (P <
      0.01), and ET-1 (P < 0.01), and attenuated the decreases in mRNA levels for HSPG
      (P < 0.01) in glomeruli of PAN-injected rats. Enalapril had little effect on
      increased glomerular mRNA levels for MMP-2 and TIMP-1 in PAN nephrosis, whereas
      FR139317 attenuated the increases in glomerular mRNA levels for MMP-2 (P < 0.01)
      and TIMP-1 (P < 0.01). CONCLUSIONS: These data suggest that the beneficial
      effects of enalapril and FR139317 may be related to modulation of glomerular mRNA
      expression of ECM components and ET-1 and that these agents may follow a
      different mechanism in regulating the glomerular mRNA expression for MMP-2 and
      TIMP-1 in PAN nephrosis.

PMID- 9175059
TI  - Continuous administration of intravenous iron during haemodialysis.
AB  - A simple, safe and potentially cost effective method of giving intravenous iron
      to patients receiving regular haemodialysis therapy is described. The heparin and
      iron are mixed in normal saline and given as a continuous infusion via the
      syringe pump present on the modern dialysis machine. No pharmacological
      incompatibility was observed between iron polymaltose and Heparin Choay or
      Heparin Roche. No adverse reactions attributable to i.v. iron were observed in
      over 400 patients and more than 30,000 dialyses.

PMID- 9175060
TI  - Ultrasound-guided cannulation of the femoral vein for acute haemodialysis access.
AB  - BACKGROUND: Central venous access is a mandatory part of patient management in
      many clinical settings and is usually achieved with a blind, external landmark
      guided technique. The purpose of this study is to evaluate whether an ultrasound
      technique can improve on the external landmark method. METHODS: We prospectively
      evaluated an ultrasound-guided method in 28 patients undergoing femoral vein
      cannulation for acute haemodialysis access and compared the results with 38
      patients in whom an external landmark-guided technique was used. External
      landmark-guided technique was done by manual localization of the femoral artery
      in the femoral triangle inferior to the inguinal ligament with needle insertion
      medial to the artery. Ultrasound-guided cannulation was performed in the same
      location with the aid of an ultrasound device (Site-Rite, Dymax Corp., USA) with
      a 7.5 MHz transducer covered by a sterile sheath. RESULTS: Cannulation of the
      femoral vein was achieved in all patients (100%) using ultrasound and in 34
      patients (89.5%) using the landmark-guided technique. The vein was entered on the
      first attempt in 92.9% of patients using ultrasound and in 55.3% using the
      landmark technique (P < 0.05). Average access time (skin to vein) was similar but
      total procedure time was 45.1 +/- 18.8 s by the ultrasound approach and 79.4 +/-
      61.7 s by the landmark approach (P < 0.05). Using ultrasound, puncture of the
      femoral artery occurred in 7.1% of patients, and haematoma in 0%. Using external
      landmark technique, puncture of the femoral artery occurred in 15.8% of patients,
      and haematoma in 2.6%. CONCLUSIONS: Ultrasound-guided cannulation of the femoral
      vein reduces the time required for the procedure, reduces the number of passes
      needed to puncture the vein, and minimizes complications such as arterial
      puncture or haematoma.

PMID- 9175061
TI  - Two different techniques and outcomes for insertion of long-term tunnelled
      haemodialysis catheters.
AB  - BACKGROUND: Renal Units employ different techniques for insertion of long-term
      haemodialysis catheters into jugular veins, and we decided to ascertain the
      success rate and peri-insertion complications of two percutaneous methods in a
      District General Hospital. METHODS: Results of venous cannulation from two
      studies using different techniques were obtained and compared. Both studies were
      prospective and the procedures were performed by the same Clinician in patients
      with end stage renal failure. Patients were divided into two groups. Group A had
      venous catheters inserted under ultrasonographic guidance using a Site Rite
      portable machine and Group B were inserted 'blind'. The aseptic percutaneous
      Seldinger technique was used for catheterizations in both groups. RESULTS: The
      first attempt/pass venous cannulation success rate was 88.6% in Group A compared
      to 61.4% in Group B. Complications rate was significantly lower in Group A (P =
      0.0048) than in Group B. CONCLUSION: In this study the ultrasonographic guided
      technique was better than the blind technique in jugular venous cannulations.

PMID- 9175062
TI  - Association of vasculitic glomerulonephritis with membranous nephropathy: a
      report of 10 cases.
AB  - BACKGROUND: The concomitant occurrence of a vasculitic glomerulonephritis and
      membranous nephropathy in the same patient is unusual. We report data on 10
      patients with this unusual combination. METHODS: Ten patients (nine males/one
      female; median age 63.5 years, range 30-70 years) presented between 1981 and 1995
      with: acute renal failure (n = 3), nephrotic syndrome (n = 4), non-nephrotic
      range proteinuria and renal insufficiency (n = 3). The median serum creatinine at
      presentation was 296 mumol/l (range 65-1749 mumol/l). One patient had a
      vasculitic transformation from membranous nephropathy 5 years after the original
      presentation, coincident with an acute deterioration of renal function requiring
      dialysis; in all other patients the two glomerular disorders were seen together
      at presentation. Treatment was with oral prednisolone and cyclophosphamide (eight
      patients), of whom one also had plasma exchange; and oral prednisolone and
      azathioprine (one patient). Specific immunosuppressive treatment was withheld in
      one patient with histological evidence of chronic renal damage. Sera from four
      patients out of nine tested were positive for ANCA. RESULTS: After a median
      follow-up of 3.5 years (range 2 months-10 years), renal function had improved in
      three patients and remained stable in two. Two patients required renal
      replacement therapy. Three patients had died: one was ANCA-negative and died of a
      systemic vasculitis, and the other two died of sepsis. CONCLUSION: Membranous
      nephropathy complicated by a vasculitic glomerulonephritis: (1) has a more
      aggressive clinical course than membranous nephropathy alone, (2) appears to have
      an association with ANCA, (3) should be considered in those patients with an
      accelerated decline in renal function, and (4) may respond to treatment with
      immunosuppressive drugs.

PMID- 9175063
TI  - Focal xanthogranulomatous pyelonephritis mimicking a renal tumor: CT- and MR
      findings and evolution under therapy.

PMID- 9175064
TI  - Reversible voltage-dependent distal renal tubular acidosis in a patient receiving
      standard doses of trimethoprim-sulphamethoxazole.

PMID- 9175065
TI  - An incidental finding--bilateral multifocal renal oncocytoma.

PMID- 9175066
TI  - Remission of a refractory nephrotic syndrome after low-density lipoprotein
      apheresis based on dextrane sulphate adsorption.

PMID- 9175067
TI  - Sporadic orofaciodigital syndrome type I presenting as end-stage renal disease.

PMID- 9175068
TI  - Idiopathic acute granulomatous interstitial nephritis leading to renal papillary
      necrosis.

PMID- 9175069
TI  - Bicarbonate haemodialysis as a treatment of metformin overdose.

PMID- 9175070
TI  - Dialysis catheter 'fibrin-sheath stripping': a cautionary tale!

PMID- 9175071
TI  - Uraemic pericarditis: a reversible inflammatory state of resistance to
      recombinant human erythropoietin in haemodialysis patients.

PMID- 9175072
TI  - Post-transplantation Kaposi's sarcoma appearing simultaneously in same cadaver
      donor renal transplant recipients.

PMID- 9175073
TI  - Haemophagocytic-histiocytic syndrome in renal transplantation.

PMID- 9175074
TI  - Calciphylaxis in two non-compliant patients with end-stage renal failure.

PMID- 9175075
TI  - A child with haemolytic uraemic syndrome: do we have to care about aetiological
      heterogeneity?

PMID- 9175076
TI  - Renal artery aneurysm and fibromuscular dysplasia.

PMID- 9175077
TI  - The patient with end-stage renal failure and ascites.

PMID- 9175078
TI  - Diagnosis and treatment of hyponatraemia in SIAD.

PMID- 9175079
TI  - Optimal treatment regimen for CAPD peritonitis caused by Rhodococcus species.

PMID- 9175080
TI  - Lupus nephritis and HCV infection.

PMID- 9175081
TI  - Effectiveness of pulse cyclophosphamide plus oral steroid therapy in idiopathic
      membranoproliferative glomerulonephritis.

PMID- 9175082
TI  - Calciphylaxis, thrombotic diathesis and defects in coagulation regulation.

PMID- 9175083
TI  - Bullous dermatosis of end-stage renal disease and aluminium.

PMID- 9175084
TI  - Anaphylactoid reactions during dextran apheresis may occur even in the absence of
      ACE-inhibitor administration.

PMID- 9175085
TI  - Contribution of frontostriatal function to sequence learning in Parkinson's
      disease: evidence for dissociable systems.
AB  - The frontostriatal system appears to play a crucial role in the organization and
      execution of sequential behaviour, but the precise nature of its contribution
      remains to be specified. From this perspective, relatively simple modifications
      of behavioural task parameters may invoke rather profound changes in the
      recruitment of appropriate neural mechanisms, including the frontostriatal
      system. This mini-review examines how variations in task requirements for
      sequence learning and related cognitive tasks can induce significant
      modifications in the performance of patients with Parkinson's disease. In
      particular, these observations are used to support a developing argument for
      neurophysiologically dissociable sequence learning systems in man. One of these
      mechanisms is sensitive to surface structure, or element-by-element sequence
      organization, and appears to rely on the frontostriatal system. Another sequence
      learning mechanism is sensitive to abstract structure, or relationships between
      repeating sequence elements, and appears to be largely independent of the
      frontostriatal system.

PMID- 9175086
TI  - Induction of TrkA receptor by retinoic acid in leukaemia cell lines.
AB  - To explore the potential involvement of neurotrophins in the actions of retinoic
      acid (RA) on leukaemia differentiation, we examined the ability of RA to regulate
      the expression of neurotrophins and Trk receptors in several leukaemia cell
      lines. Expression of TrkA was dramatically induced by RA at both the mRNA and
      protein level in leukaemia cell lines K562 and KG-1. Furthermore, while no
      expression of trkB and trkC was detected, constitutive expression of nerve growth
      factor (NGF), neurotrophin-3 and neurotrophin-4/5 could be detected in leukemia
      cells. Our findings suggested that NGF/trkA may potentially be involved in the RA
      induced differentiation of leukemia cells.

PMID- 9175087
TI  - Apparent asynchrony between interictal electric and magnetic spikes.
AB  - We recorded simultaneous multichannel electroencephalogram (EEG) and
      magnetoencephalogram (MEG) in four children with partial epilepsy. Sources of
      averaged spikes were modelled with current dipoles. Of 10 spike averages
      obtained, three peaked simultaneously in MEG and EEG, and in seven averages, the
      MEG peak preceded the main EEG peak by 9-40 ms. A small positive early EEG signal
      coincided with the MEG peak in six asynchronous spikes. The simultaneous MEG and
      EEG spikes originated within 5-23 mm, while sources of asynchronous peaks were 12
      67 mm apart. We conclude that non-identical neurone currents underlie the MEG and
      EEG signals, and emphasize the importance of modelling early phases of EEG spikes
      when localizing interictal epileptic zones.

PMID- 9175088
TI  - Scavenger receptor mRNAs in rat brain microglia are induced by kainic acid
      lesioning and by cytokines.
AB  - The expression and localization of two distinct mRNAs from the macrophage
      scavenger receptor gene family were studied in rat brain cells in vivo and in
      vitro. In general, brains of control male rats showed low level signals by in
      situ hybridization for the macrophage scavenger receptor (MSR) and murine
      adherent macrophage (MAMA) receptor. In contrast, the reticular thalamic nucleus
      had a subpopulation of intensely labeled cells. Kainic acid (KA) treatment
      induced MSR and MAMA mRNA levels on different schedules in brain regions that are
      susceptible to KA, including hippocampal areas CA1 and CA3. The combination of
      immunocytochemistry and in situ hybridization localized the MSR and MAMA mRNA to
      microglia of KA-treated rats. Northern blot hybridization detected both MSR and
      MAMA mRNAs in primary cultures of mixed glia that contained microglia. Both MSR
      and MAMA mRNA were induced by treatment of primary mixed glia with
      lipopolysaccharide and interferon-gamma, but not TGF beta 1. MSR, but not MAMA,
      mRNA levels were increased after treatment with interleukin-1 alpha. These
      results demonstrate the differential regulation of scavenger receptor mRNAs in
      microglia that is consistent with distinct roles for scavenger receptors in
      responses to neurodegeneration.

PMID- 9175089
TI  - Expression of the P2X2 receptor subunit of the ATP-gated ion channel in the
      retina.
AB  - The site of extracellular ATP signalling in the retina was investigated by
      examining expression of the P2X2 receptor (P2X2R) subunit which assembles to form
      ATP-gated ion channels. Indirect in situ RT-PCR in situ hybridization localized
      the presence of mRNA for the P2X2R subunit within the soma of photoreceptors,
      inner nuclear layer neurones and the retina ganglion cells. Use of an antiserum
      specific for the P2X2R subunit confirmed the expression of the protein by these
      cells and demonstrated a particularly dense immunolabelling within the inner
      plexiform layer containing the dendritic processes of the retina ganglion cells.
      The outer segment of the photoreceptors also exhibited P2X2R-like
      immunoreactivity. The extensive expression of ATP-gated ion channel protein
      within the retina suggests that extracellular ATP plays diverse neurohumoral
      roles in regulation of visual processing and cellular homeostasis.

PMID- 9175090
TI  - Dopaminergic regulation of BDNF content in the pituitary intermediate lobe.
AB  - Previous studies in adult rats have demonstrated that the neurotrophin, brain
      derived neurotrophic factor (BDNF), is present in virtually all cells of the
      pituitary intermediate lobe. In the present study, we demonstrate that cells
      cultured from adult intermediate lobe pituitary (ILP) rapidly lose their BDNF
      immunoreactivity (IR). Furthermore, a similar loss of immunostaining occurs in
      whole (undissociated) ILP within 30 min after removal from the rat. However, when
      the dopamine agonist apomorphine is present throughout the dissociation procedure
      and during cultivation, BDNF-IR is preserved. Supplying apomorphine only during
      either dissociation or cultivation did not prevent the loss of BDNF-IR in the 24
      h cultures. These results suggest that a tonic dopaminergic stimulus is required
      to maintain BDNF-IR in ILP cells.

PMID- 9175091
TI  - Effects of discrimination learning on the rat striatal dopaminergic activity: a
      microdialysis study.
AB  - The prefrontal cortex (PFC) has anatomical and functional relationships with the
      striatum. In a previous study we showed that dopamine (DA) turnover in the PFC of
      rats is enhanced during the performance of a discrimination task. In the present
      study, we used an in vivo microdialysis method to examine whether DAergic
      activity in the striatum could also be altered by the discrimination task. The
      results showed a substantial and sustained suppression of DAergic activity during
      and after the discriminative behaviour. The fact that the discriminative
      performance induced opposite changes in DAergic activity in the striatum and the
      PFC is consistent with the results of biochemical studies, suggesting that the
      suppressed DA turnover in the striatum may be induced by the enhanced DAergic
      activity in the PFC during the discrimination task.

PMID- 9175092
TI  - A role for calcineurin in the desensitization of the P2X3 receptor.
AB  - The sensory neurone-specific ATP-gated cation channel P2X3, when expressed in
      Xenopus oocytes, desensitizes rapidly. Complete removal of extracellular calcium
      abolishes desensitization. Pretreatment of oocytes with cyclosporin also
      abolishes P2X3 desensitization. When the calcineurin auto-inhibitory peptide (CaN
      A457-481) was injected into oocytes, the rate of desensitization of P2X3
      decreased on consecutive applications of ATP, suggesting a role for calcineurin
      in the regulation of desensitization. Truncated P2X3 clones initiating at Met-75
      lack the N-terminal intracellular region, but express functional channels in
      oocytes that do not desensitize. Taken together, these data suggest that P2X3
      desensitizes through a calcium-dependent calcineurin-mediated dephosphorylation
      involving N-terminal residues that are phosphorylated in functional channels.

PMID- 9175093
TI  - Combined EEG and MEG recordings of visual 40 Hz responses to illusory triangles
      in human.
AB  - EEG and MEG were simultaneously recorded to study the visual gamma-band (30-70
      Hz) responses. The electrical gamma-band response phase-locked to stimulus onset
      can be subdivided into a central component at 39 Hz and an occipital component at
      36 Hz. A new high-frequency magnetic phase-locked response recorded over the
      occipital lobe is described. Its topography is complex and probably reflects the
      activity of multiple sources. Both electrical and magnetic high-frequency
      responses differ in topography from the low-frequency responses in the same
      latency range, suggesting that at least partially distinct sources are involved.
      The existence of a non-phase-locked 40 Hz component around 280 ms is confirmed in
      EEG data but is not detectable in MEG data.

PMID- 9175094
TI  - Brain glucose: voltammetric determination in normal and hyperglycaemic rats using
      a glucose microsensor.
AB  - Pulsed voltammetry applied to glucose oxidase-coated carbon fibre electrodes
      (glucose sensor) was used for brain glucose determination in normal and
      streptozotocin-treated rats (experimental diabetes mellitus). Glucose levels
      increased in the frontal cortex of diabetic animals compared with the controls
      (+262%). Glucose levels were also increased in their CSF (+48%) and plasma
      (+64%), determined in ex vivo conditions. The validity of the glucose sensor
      determinations, as well as that of the experimental model of diabetes used, was
      checked using the Beckman glucose analyser and a radioimmunoassay for plasma
      insulin. Insulin, unlike glucose, was decreased in diabetic animals. The sensor
      described here ensures precise determinations and is suitable for use in
      experimental models where alterations in glucose metabolism occur.

PMID- 9175095
TI  - Different roles of the left and right parahippocampal regions in verbal
      recognition: a PET study.
AB  - We examined the role of the parahippocampal regions in humans during two types of
      verbal recognition process, i.e. delayed matching and non-matching, by measuring
      regional cerebral blood flow (rCBF) using PET. The results showed differential
      activation of each parahippocampal region during verbal memory tasks in which the
      side activated shifted depending on the nature of the task employed; an increase
      in rCBF in the left parahippocampal gyrus was associated with retrieval strategy
      of non-matching, and an increase in rCBF in the right parahippocampal gyrus was
      associated with retrieval strategy of matching. We conclude that lateralized
      parahippocampal activation may depend on the type of response required.

PMID- 9175096
TI  - Hypersensitivity of lurcher mutant mice to the depressing effects of
      lipopolysaccharide and interleukin-1 on behaviour.
AB  - Lurcher mutant mice are characterized by a fast and almost total loss of
      olivocerebellar neurones during the first postnatal month, associated with a
      chronic inflammatory state. To test their brain sensitivity to proinflammatory
      cytokines, we assessed the behavioural responses of adult male Lurcher and wild
      type to an i.p. or i.c.v. injection of rat recombinant IL-1 beta, and
      lipopolysaccharide (LPS). IL-1 beta (15 micrograms kg-1, i.p. or 1 ng i.c.v.)
      decreased social exploration measured 2, 4 and 6 h later, and this decrease was
      significantly more pronounced in Lurcher than in wild type mice. LPS (60
      micrograms kg-1, i.p. or 5 ng i.c.v.) decreased social exploration measured 2 and
      4 h later, and this effect was also significantly more marked in Lurcher than in
      wild type mice. These results suggest that the chronic inflammatory state which
      characterizes Lurcher mice renders these animals more sensitive to the effects of
      cytokines such as IL-1 beta and LPS. This difference may be due to the higher
      reactivity of brain macrophages and glial cells to LPS and IL-1 in Lurcher mice
      than in wild type.

PMID- 9175097
TI  - Trigeminovascular stimulation in conscious rats.
AB  - Intracisternal infusion of capsaicin was used to induce intracranial
      trigeminovascular stimulation in conscious rats. Both behaviour and trigeminal
      nucleus caudalis c-fos expression were examined. Exploratory behaviour was dose
      dependently reduced and different types of behaviours were induced with various
      doses of capsaicin. Head grooming and scratching show that intracranial
      activation of trigeminal afferents can be referred as extracranial trigeminal
      stimulation. Analysis of behaviour exhibited during trigeminovascular stimulation
      may provide a powerful tool to study effects of central acting anti-migraine
      drugs.

PMID- 9175098
TI  - High density lipoprotein decreases beta-amyloid toxicity in cortical cell
      culture.
AB  - A hallmark of Alzheimer's disease (AD) is the extracellular deposition and
      accumulation of a 39-43 amino peptide, known as the amyloid beta (A beta)
      protein, within the brain. It has been postulated that A beta may in some way
      contribute directly to AD pathogenesis. The epsilon 4 allele of apolipoprotein E
      (apoE) is a major AD risk factor. Since both apoE and A beta are components of
      lipoproteins in plasma and cerebrospinal fluid, we asked whether lipoproteins and
      apoE isoforms would modify the toxicity of A beta (1-42) in cortical cell
      cultures. We show that high density lipoprotein with or without apoE reduces A
      beta toxicity and that apoE in the absence of lipoproteins does not affect A beta
      toxicity. These results suggest that interactions between A beta and lipoproteins
      in the brain could influence AD pathogenesis.

PMID- 9175099
TI  - Stimulation of corticotrophin-releasing hormone release by the obese (ob) gene
      product, leptin, from hypothalamic explants.
AB  - Recent data have suggested that adipocytes synthesize and secrete a 16 kDa
      peptide which acts centrally to regulate weight gain by suppressing appetite and
      activating the sympathetic nervous system. To exert such effects, it may function
      as an endogenous ligand in the CNS, since specific receptors (OB-R) have been
      recently reported to be widely distributed in the brain. We have speculated that
      this peptide, now known as leptin, may act centrally by stimulating the release
      of corticotrophin-releasing hormone (CRH), a recognized potent inhibitory
      modulator of appetite. We tested in vitro the effect of murine leptin on CRH
      secretion in the dose range of 0.1 pM-100 nM. The static rat hypothalamic
      incubation system used involved fresh hypothalamic explants maintained in EBSS
      with consecutive 20 min incubations, and estimation of CRH concentrations in the
      medium by a specific and sensitive radioimmunoassay. The effect of heat-denatured
      leptin at a dose of 1 nM and 10 nM, was also investigated. Any possible
      modulation of leptin effects by adrenergic pathways was then explored by
      coincubating hypothalami with leptin 10 nM and equimolar concentrations of the
      alpha 1-adrenergic antagonist prazosin or the beta-adrenergic antagonist
      propranolol. The active leptin, but not the heat-inactivated peptide, caused a
      dose-dependent stimulation of CRH release in vitro (p < 0.05- < 0.0001 vs
      control), with a plateau effect at a dose of 10 nM. The addition of either
      prazosin or propranolol was without effect on leptin-dependent CRH stimulation.
      These findings are consistent with the reported presence of leptin receptors in
      the rat brain, and suggest that leptin may act to regulate appetite at least in
      part by directly modulating the secretion of CRH from the hypothalamus. It would
      also appear that such effect occurs via a non-adrenergic mechanism.

PMID- 9175100
TI  - Possible involvement of neuropeptidergic sensory nerves in alopecia areata.
AB  - Alopecia areata (AA) is a dermatosis involving the sudden occurrence of bald
      patches on the scalp. Although the aetiology is unknown, experimental data
      indicate that cutaneous microcirculation plays an important role. The skin is
      richly innervated by neuropeptidergic sensory nerves that help regulate
      microvascular circulation. This study shows a reduction of cutaneous levels of
      substance P and calcitonin gene-related peptide (CGRP) but not of vasoactive
      intestinal polypeptide in scalp biopsies from patients with AA. Laser-Doppler
      flowmetry was used to study microcirculation of the scalp. Results indicate that
      patients with AA have lower basal blood flow and greater vasodilatation following
      intradermal CGRP injection than control subjects. A vascular hyper-reactivity to
      vasodilatatory substances such as neuropeptides, probably because of the lack of
      these substances, is hypothesized.

PMID- 9175101
TI  - Glycine antagonism does not block ischemic spontaneous depolarization in the rat.
AB  - This study examined the effect of glycine recognition site antagonism (ACEA 1021)
      on the incidence of spontaneous depolarizations in the penumbra of a focal
      ischemic lesion. Rats were administered either vehicle (n = 7), ACEA 1021 (n = 7)
      or dizocilpine (n = 5) and then underwent 90 min middle cerebral artery
      occlusion. The cortical direct current (DC) potential was recorded. During
      ischemia, 7 +/- 3 DC shifts occurred in the vehicle group. ACEA 1021 did not
      reduce this frequency (7 +/- 2 DC shifts) although dizocilpine did (1 +/- 1 DC
      shifts; p = 0.02). The previously demonstrated neuroprotective property of ACEA
      1021 during focal cerebral ischemia cannot be attributed to reduction of
      spontaneous depolarization in the ischemic penumbra.

PMID- 9175102
TI  - Hypoxia in striatal and cortical neurones: membrane potential and Ca2+
      measurements.
AB  - Simultaneous measurements of membrane potential and intracellular Ca2+ were used
      to study the effects of hypoxia on striatal and cortical neurones. Striatal
      neurones responded to hypoxia with a reversible membrane depolarization coupled
      with a transient increase in intracellular Ca2+. Thirty minutes of hypoxia caused
      an irreversible membrane depolarization associated with a massive raise in Ca2+
      levels, leading to cell death. Conversely, cortical neurones were more resistant
      to O2 deprivation. Hypoxia (4-10 min) induced minimal changes in both membrane
      potential and Ca2+ signals. Longer periods (20-30 min) caused an initial membrane
      hyperpolarization followed by a large but reversible depolarization coupled with
      a transient increase in Ca2+ signals. These results support the hypothesis of a
      differential sensitivity of central neurones to hypoxia, suggesting that striatal
      neurones are more vulnerable than cortical cells.

PMID- 9175103
TI  - Progressive focal neurological dysfunction following experimental implantation
      glioma.
AB  - One of the difficulties in understanding peritumoural brain dysfunction is the
      lack of defined clinical deficits in experimental glioma models. In this study
      progressive focal neurological dysfunction was measured using the staircase test
      in rodents subjected to striatal implantation of C6 glioma cells. After 22 days
      none of the animals, all of which had cortico-striatal tumours ranging in size
      from 93 to 140 mm3, showed any obvious gross behavioural abnormality. However,
      contralateral forelimb function was significantly worse than that before surgery
      by day 7 (p < 0.01) and worse than sham-implanted animals by day 12 (p < 0.01).
      Using this experimental paradigm the staircase test can be used to measure
      progressive focal neurological deterioration and evaluate both the mechanisms of,
      and therapies for peritumoural brain dysfunction.

PMID- 9175104
TI  - Neuronal correlates of auditory induction in the cat cortex.
AB  - Cells in the cat primary auditory cortex (A1) were investigated to see whether
      they could integrate sound signals over time. A1 cells responded well to
      frequency-modulated sweeps. When a portion of the sweep was replaced by silence
      the response was weakened considerably. However, the response strength was
      restored when the silent portion was replaced by a burst of band noise, even
      though the cells did not respond to the burst of noise alone. These results
      indicate that A1 cells do not respond simply to instantaneous characteristics of
      acoustic stimuli but respond to those integrated over time.

PMID- 9175105
TI  - Induction of cyclo-oxygenase 2 in brains of patients with Down's syndrome and
      dementia of Alzheimer type: specific localization in affected neurones and axons.
AB  - Immunohistochemical and immunoblotting studies with an antibody against cyclo
      oxygenase 2 (COX2) were performed in the cerebral cortex of patients with Down's
      syndrome (DS) and dementia of Alzheimer type (DAT). A high level of COX2
      expression was observed in DAT and older DS patients, specifically localized in
      neurones with neurofibrillary tangles (NFT) and damaged axons. Furthermore,
      immunohistochemical study of patients with DS of varying age showed that the
      induction of COX2 correlated well with the appearance of NFT as well as with
      ageing. These findings demonstrated the induction of COX2 in DAT and DS, which
      may lead to the production of free radicals and may be causally related to
      neuronal degeneration.

PMID- 9175106
TI  - Brain cell microenvironment effects on neuron excitability and basal metabolism.
AB  - In a model of neurons in a brain cell assembly, changes in volume of the
      extracellular space affect neuronal excitability and basal metabolism. A widely
      applicable coefficient of excitability with respect to a variation of the volume
      fraction has been determined. Calculations suggest that chloride increases
      membrane stability by indirectly promoting an acceleration of the metabolic
      pumping rate as a response to a diminished extracellular volume fraction. Volume
      fraction changes induced by cell swelling in a compact and highly tortuous
      microenvironment may play a role in epilepsy and, following brain damage, in cell
      death and recovery.

PMID- 9175107
TI  - Effect of dexamethasone on voltage-gated Ca2+ channels and cytosolic Ca2+ in rat
      chromaffin cells.
AB  - The present study examined whether the synthetic glucocorticoid dexamethasone
      (DEX) can modulate voltage-gated Ca2+ channel (VGCC) activity, and as a
      consequence agonist-induced increases in cytosolic Ca2+, in cultured rat adrenal
      medullary chromaffin (RAMC) cells. Exposure to 1 microM DEX for 48 h
      significantly increased peak VGCC current (delta +140%). DEX treatment also
      significantly potentiated the increases in cytosolic Ca2+ in response to
      submaximal stimulatory concentrations of KCl (delta +64%) and nicotine (delta
      +32%). The Ca2+ channel agonist BAY K-8644 increased both VGCC current (delta
      +109%) and potentiated the KCl-stimulated increase in cytosolic Ca2+ (delta +35%)
      to a comparable extent to that seen with DEX. These data suggest that DEX
      treatment increases VGCC activity, and that this increased Ca2+ influx leads to
      potentiation of agonist-induced increases in cytosolic Ca2+ in RAMC cells.

PMID- 9175108
TI  - Scopolamine-induced deficits in a two-trial object recognition task in mice.
AB  - The purpose of the present study was to design an object recognition task in mice
      and characterize the effects of scopolamine in this paradigm. This task consisted
      of exposing mice for 6 or 10 min to an object in an open field (trial 1) and,
      after a delay (1-24 h), testing mice for 10 min with the object and a novel
      object (trial 2). Mice explored the novel object more than the familiar object as
      the inter-trial delay decreased and/or the duration of trial 1 increased.
      Administration of scopolamine (0.3, 1 and 3 mg kg-1, s.c.) before trial 1 reduced
      recognition performance on trial 2 after a 3 h inter-trial delay and induced
      other behavioural effects, including an increase in locomotor activity on trial
      1. Methylscopolamine (1 mg kg-1) had no effect on recognition performance. The
      present results show that this task is a useful model to test recognition memory
      in mice and that blocking the central cholinergic system impairs this form of
      memory.

PMID- 9175109
TI  - Dependence of synaptic facilitation postsynaptically induced in snail neurones on
      season and serotonin level.
AB  - The problem of stability of long-lasting synaptic facilitation postsynaptically
      induced by intracellular current pulses without concomitant presynaptic
      activation was addressed. A short (15-20 min) phase of synaptic facilitation
      induced by intracellular tetanization in identified snail neurones was stable and
      present in all experiments, while a long-term phase (lasting > or = 50 min) was
      observed only some experiments. Data analysis revealed dependence of the long
      term phase on season. Dependence of the long-term phase of facilitation on
      serotonin concentration in hemolymph, which is known to change with season, was
      shown using the selective neurotoxin 5,7-dihydroxytriptamine. Dependence of
      habituation rate in the same synaptic connection on season and serotonin level
      was shown.

PMID- 9175110
TI  - Slow wave sleep is accompanied by release of certain amino acids in the thalamus
      of cats.
AB  - To determine whether EEG synchronization in sleep has a metabolic equivalent, we
      investigated state-dependent changes in extracellular concentrations of amino
      acids. In vivo microdialysis studies were performed in the ventroposterolateral
      (VPL) nuclei of the thalamus of cats during natural slow wave sleep (SWS), waking
      (W) and carbachol-induced paradoxical sleep (PS) like episodes. About two-fold
      increases in aspartate, glutamate, asparagine, glycine, alanine and gamma
      aminobutyric acid (GABA) were observed in SWS compared with control samples
      collected in W, but serine increased to 487 +/- 211%. In the PS-like state,
      glutamine increased and GABA decreased. These results suggest changes in
      intracellular processes reflected by amino acid release in the thalamus, specific
      to slow wave generation in EEG during natural sleep.

PMID- 9175111
TI  - Cortical direction selectivity without directional experience.
AB  - How neurones in the visual cortex acquire their response properties during
      postnatal development is an important question with far-reaching implications. In
      the present study, we demonstrate the developmental specification of geniculo
      cortical afferents using our previously proposed model for the activity-dependent
      self-organization of neural networks. Our results indicate, in contrast to common
      beliefs, that both orientation and direction selectivity can be achieved in the
      primary visual cortex even if the retinae were never exposed to oriented and/or
      moving objects during development.

PMID- 9175112
TI  - Mossy fibre sprouting: evidence against a facilitatory role in epileptogenesis.
AB  - Sprouting of mossy fibres from dentate granule cells occurs in several animal
      models of epilepsy and in epileptic humans. Mossy fibre sprouting might
      contribute to epileptogenesis but also could be a compensatory, inhibitory
      response. We analysed mossy fibre sprouting in the supragranular zone of the
      dentate gyrus using Timm's histochemical method in genetically fast and slow
      kindling rats. Before the start of amygdala kindling, the slow rats showed higher
      Timm's staining scores than did the fast kindlers. No increase of mossy fibre
      density was observed when the animals were stimulated until either the fast or
      the slow rats had reached the fully kindled state. Our data argue against the
      hypothesis that mossy fibre sprouting facilitates epileptogenesis.

PMID- 9175113
TI  - beta Amyloid does not activate the antioxidant pentose phosphate pathway within
      the B12 neural cell line.
AB  - The aim of this study was to determine whether neural cells exposed to beta
      amyloid (A beta) activate the pentose phosphate pathway (PPP), a critical
      oxidative stress defense mechanism. A beta stimulated H2O2 production in neural
      (B12) and non-neural (HepG2) cells and stimulated PPP activity, the source of the
      main intracellular reductant NADPH, in HepG2 cells (67% increase). Catalase
      blocked the A beta-induced increase in PPP, demonstrating that H2O2 mediated the
      increase in PPP activity. B12 cells showed no increase in PPP following A beta
      exposure. Fifty-five per cent of HepG2 cells but only 11.1% of B12 cells remained
      viable after A beta exposure. Lack of PPP activation may contribute to A beta
      cytotoxicity in neural calls and may lead to differences in survival between
      neural and non-neural cells.

PMID- 9175115
TI  - Abnormalities of predictive saccades in Parkinson's disease.
AB  - Saccades of patients with mild Parkinson's disease (PD) are said to be abnormal
      in the absence of a concurrently visible target or when they are part of a rapid
      sequence of eye movements. We tested this hypothesis using a predictive saccade
      paradigm in which target visibility is withdrawn for a period. Three rates of
      target alternation were used (0.25 Hz, 0.5 Hz and 1.0 Hz). Withdrawal of target
      visibility brought out the extremes of primary saccade gain for both the controls
      and the patients with PD, most undershoot being displayed at the lowest
      frequency, whereas the gain was greatest at the highest frequency, actually
      overshooting the target location. These results demonstrate that the spatial
      error of parkinsonian saccades does not invariably take the form of hypometria
      when part of a rapid sequence of eye movements.

PMID- 9175114
TI  - Vagal activity predicts eyeblink conditioning in human subjects.
AB  - A group of old (mean age 73 years) and young (mean age 19.8 years) human subjects
      received concomitant eyeblink and heart rate classical conditioning, in which a
      1000 Hz tone was the conditioning stimulus and a corneal airpuff was the
      unconditioned stimulus. Fewer old than young subjects showed eyeblink
      conditioning and age greatly attenuated the magnitude of the brady-cardiac
      conditioned heart rate response. The heart rate conditioned response was also
      significantly smaller in the subjects who failed to show eyeblink conditioning
      regardless of age, suggesting a relationship between parasympathetic cardiac
      control and somatomotor learning. The power associated with the respiratory peak
      in the heart rate spectrum, which is vagal in origin, was also smaller in
      subjects that failed to show eyeblink conditioning, again suggesting a
      relationship between parasympathetic cardiac activity and motor learning.

PMID- 9175116
TI  - Expression and distribution of CC chemokine macrophage inflammatory protein-1
      alpha/LD78 in the human brain.
AB  - Macrophage inflammatory protein (MIP)-1 alpha, also known as LD78, is a member of
      a family of chemokines which recruit leukocytes to sites of inflammation. We have
      shown by Northern blot analyses that MIP-1 alpha mRNA is expressed in several
      human tissues, including brain. To explore MIP-1 alpha distribution in brain
      tissue, we immunohistochemically examined brain tissues from 13 neuropsychiatric
      patients. Glial cells in the white matter of brain tissues from four patients
      with schizophrenia and one with manic depressive illness were MIP-1 alpha
      positive. Glial cells in the cortex from these patients were negative, except in
      one patient with schizophrenia in whom neurones as well as glial cells in the
      cortex stained positively for MIP-1 alpha. In situ hybridization showed that MIP
      1 alpha mRNA was expressed in both neurones as well as glial cells in this
      patient. These results suggest a heterogeneous distribution of MIP-1 alpha in
      human brain.

PMID- 9175117
TI  - AII amacrine cells express functional NMDA receptors.
AB  - NMDA and non-NMDA receptors mediate the majority of fast excitatory synaptic
      transmission in the CNS. AII amacrine cells in the mammalian retina receive
      glutamatergic input from rod bipolar cells and are known to express non-NMDA
      receptors. We have investigated the expression of NMDA receptors in these cells
      by recording responses to exogenously applied NMDA in whole-cell recordings in
      slices of rat retina. Most cells displayed clear responses to NMDA. The responses
      could be blocked by a specific NMDA receptor antagonist and were characterized by
      voltage-dependent block with outward rectification. These results suggest that
      NMDA receptors could play a role in mediating excitatory synaptic input to AII
      amacrine cells.

PMID- 9175118
TI  - Activation of the human brain by monetary reward.
AB  - With the purpose of studying neural activation associated with reward processing
      in humans, we measured regional cerebral blood flow in 10 right-handed healthy
      subjects performing a delayed go-no go task in two different reinforcement
      conditions. Correct responses were either rewarded by money or a simple "ok'
      reinforcer. Behaviour rewarded by money, as compared with the "ok' reinforcement,
      was most significantly associated with activation of dorsolateral and orbital
      frontal cortex and also involved the midbrain and thalamus. These results may
      reflect the processing of reward information, although arousal effects cannot be
      completely excluded. It is suggested that the observed foci are implicated in the
      assessment of consequences in goal-directed behaviour which agrees with research
      in non-human primates.

PMID- 9175119
TI  - Relationship between BDNF- and trk-expressing neurones in rat dorsal root
      ganglion: an analysis by in situ hybridization.
AB  - Brain-derived neurotrophic factor (BDNF) is synthesized in sensory neurones and
      suggested to operate on these same neurones by an autocrine mechanism, but it is
      unclear whether these neurones express the functional receptor (TrkB) for BDNF.
      We therefore examined the co-localization of BDNF and neurotrophin receptor mRNAs
      in adult rat dorsal root ganglion (DRG) neurones by in situ hybridization
      histochemistry. BDNF mRNA signals were detected in about 40-50% of DRG neurones
      (L4-5). Almost all the trkA mRNA-expressing neurones (95%) were positive for BDNF
      mRNA, while no trkB mRNA- and few trkC mRNA-expressing neurones displayed BDNF
      mRNA signals. These findings suggest that BDNF is mainly synthesized in the
      sensory neurones that are responsive to nerve growth factor but not to BDNF or
      neurotrophin-3. It is unlikely that BDNF is involved in an autocrine loop in
      sensory ganglia.

PMID- 9175120
TI  - The apolipoprotein E epsilon 4 allele is not associated with early onset temporal
      lobe epilepsy.
AB  - A polymorphism of the apolipoprotein E gene, in particular the epsilon 4 allele
      (ApoE4), has been associated with impaired neuronal phospholipid metabolism and
      synapse reorganization and has been implicated in several neurodegenerative
      disorders. Since selective neuronal cell lose and aberrant axonal reorganization
      represent hall-marks of Ammon's horn sclerosis (AHS) in patients with chronic
      temporal lobe epilepsy (TLE), the ApoE polymorphism was studied in 125 patients
      with TLE. The genotype analysis revealed a frequency of 15.5% for epsilon 4, and
      74.8% and 9.8% for epsilon 3 and epsilon 2, respectively. These figures were not
      significantly different from those reported in the normal European population. In
      addition, no correlation was found between the ApoE4 allelotype and the age of
      epilepsy onset, seizure type, febrile seizures, family history of epilepsy,
      surgical outcome and neuropathological findings in patients with TLE. These data
      virtually exclude ApoE as a susceptibility gene involved in the pathogenesis of
      early onset TLE or AHS.

PMID- 9175121
TI  - Gene expressions of ubiquitin and hsp70 following focal ischaemia in rat brain.
AB  - Expression of genes coding for ubiquitin and heatshock protein (hsp) 70 were
      examined by in situ hybridization using a rat model with permanent occlusion of
      the distal middle cerebral artery (MCA). Only polyubiquitin (UbC) mRNA increased
      markedly following ischaemia in the central zone of the MCA territory of the
      neocortex. UbC gene expression reached the maximum level 4 h post-occlusion and
      remained elevated at 24 h. UbC expression was retarded slightly compared with
      that of the hsp70 gene. UbB and Ub-S30 were expressed at almost similar levels in
      both the ischaemic and non-ischaemic hemispheres. These results indicated that
      UbC probably has the most stress-inducible characteristics among the three
      ubiquitin genes.

PMID- 9175122
TI  - Regional decreases [corrected] in AMPA receptor density in mice infected with the
      LP-BM5 murine leukemia virus.
AB  - The status of alpha-amino-3-hydroxy-5-methyl-4-isoxizole (AMPA) receptors in
      several brain regions was investigated in a murine model of retrovirus-associated
      cognitive impairment, the LP-BM5 infected mouse. The Bmax of [3H]AMPA receptors
      in the cortex, striatum, hippocampus and cerebellum declined by 29-50% as early
      as 8 weeks post-inoculation. Immunohistochemistry revealed foci of decreased
      glutamate receptor (GluR)-2/3 protein expression by Purkinje neurons distributed
      throughout the cerebellum. Immunoblots indicated that cerebellar expression of
      only GluR-3 protein was reduced. This global decrease in AMPA receptors may
      constitute a compensatory response to elevated excitotoxin (glutamate)
      concentrations and are concurrent with the development of spatial learning
      deficits observed in these mice. Thus, the reduction in AMPA receptor density may
      contribute to the development of the cognitive abnormalities associated with
      infection by retroviruses such as HIV-1.

PMID- 9175123
TI  - Carrageenan-induced hyperalgesia is associated with increased cyclo-oxygenase-2
      expression in spinal cord.
AB  - The discovery of the inducible form of cyclo-oxygenase, known as cyclo-oxygenase
      2 (COX-2), has provided insight into the mechanisms involved in the inflammatory
      response. Peripheral inflammation induced by intraplantar injection of
      carrageenan is associated with a marked increase in COX-2 mRNA and prostaglandins
      in the surrounding tissue and the accompanying oedema is sensitive to COX-2
      selective drugs. In this study, we investigated whether COX-2 in spinal cord was
      similarly induced by carrageenan and whether the associated development of
      altered pain sensitivity, hyperalgesia was affected by the COX-2 selective
      inhibitor DuP 697. Intraplantar injection of carrageenan caused a marked
      hyperalgesia at 4 h which was significantly attenuated by treatment with DuP 697
      (10 mg kg-1). At the same time levels of COX-2 mRNA in lumbar spinal cord were
      significantly increased two-fold by carrageenan treatment. However, DuP 697
      potentiated COX-2 mRNA induction, which indicates the existence of a potential
      regulatory mechanism to overcome COX-2 inhibition.

PMID- 9175124
TI  - Voltage-activated sodium currents in acutely isolated mouse vestibular ganglion
      neurones.
AB  - Voltage-activated sodium currents (INa) in vestibular ganglion neurones acutely
      isolated from postnatal mice were investigated using the whole-cell configuration
      of the patch-clamp technique. Under recording conditions designed to allow the
      complete isolation of INa depolarizations from a holding potential of -80 mV
      revealed a fast inactivating inward current which was activated around -60 mV and
      exhibited maximum peak current around -30 mV. This current was eliminated when
      the cells were perifused with a Na(+)-free solution and almost totally blocked by
      application of 100 nM tetrodotoxin (TTX). These properties identify this inward
      current as TTX-sensitive INa. The half-maximum activation potential of INa was 
      46 mV and its half-maximum inactivation potential was -69 mV. This is the first
      report of voltage-activated sodium currents in vestibular primary neurones.

PMID- 9175125
TI  - Sequential activity in human motor areas during a delayed cued finger movement
      task studied by time-resolved fMRI.
AB  - Activity in the human primary motor cortex, the premotor cortex and the
      supplementary motor area during a delayed cued finger movement task was measured
      by time-resolved functional magnetic resonance imaging. Activity during movement
      preparation can be resolved from activity during movement execution in a single
      trial. All three areas were active during both movement preparation and movement
      execution. Activity in the primary motor cortex was considerably weaker during
      movement preparation than during movement execution; in the premotor cortex and
      the supplementary motor area, activity was of similar intensity during both
      periods. These observations are consistent with results from single neuronal
      recording studies in primates.

PMID- 9175126
TI  - Corticocortical connections between area 21a and primary visual cortex in the
      cat.
AB  - We investigated the corticocortical connections between area 21a and ipsilateral
      areas 17 and 18 in the cat. The anterograde/retrograde fluorescent tracer
      tetramethyl-rhodamine conjugated to dextran (Fluoro-Ruby) was injected into area
      21a of the anaesthetized cat. Cell bodies labelled retrogradely from area 21a
      were consistently observed in both areas 17 and 18, primarily located in the
      supragranular layers of cortex where they formed discrete patches of cells.
      Similar numbers of cell bodies were labelled retrogradely in areas 17 and 18 of
      each animal. Our data are also consistent with previous reports of a reciprocal
      projection from area 21a back to areas 17 and 18 terminating principally in
      infragranular cortical layers.

PMID- 9175127
TI  - Regulation of beta- and gamma-actin mRNA by thyroid hormone in the developing rat
      brain.
AB  - The relative sensitivity of the two isotypes of actin mRNA (beta and gamma) to
      thyroid hormone (T3) was examined by comparing the steady state levels of these
      mRNAs with their rates of transcription in cerebra from normal and hypothyroid
      rats of different ages, covering the period of synaptogenesis (days 1-20
      postnatal). Hypothyroidism was associated with a reduction in the steady state
      level of beta-actin mRNA during the entire period, but levels of gamma-actin mRNA
      were reduced only during the early phase of synaptogenesis (first week). The rats
      of transcription of both beta- and gamma-actin mRNAs were stimulated by T3 during
      the early phase but that of beta-actin mRNAs was relatively more sensitive to T3
      than gamma-actin mRNA. The lack of correlation between the rates of transcription
      of beta- and gamma-actin mRNA at different ages with their corresponding steady
      state levels suggests additional post-transcriptional regulation.

PMID- 9175128
TI  - Time estimation as a neuronal network property: a lesion study.
AB  - The neural substrate of estimating short temporal intervals is still unknown. We
      investigated the ability of patients with infarctions of the middle cerebral
      artery of either the left or the right hemisphere to estimate verbally and
      produce time intervals of seconds by counting. Patients showed long-lasting and
      stable deficits in time estimation in both methods, with either extreme
      acceleration or deceleration in apparent time compared with healthy controls. A
      lesion of the posterior part of the supralenticular white matter proved to be
      responsible for these deficits. Disruption of interneuronal communication
      therefore leads to a lasting alteration of a learned time-pacing synchronized to
      conventional time units.

PMID- 9175129
TI  - The role of phospholipase C in arginine vasopressin secretion by rat hypothalami
      in vitro.
AB  - The role of phosphatidylcholine (PC) and phosphatidylinositol (PI) specific
      phospholipase C (PLC) enzymes in the release of immunoreactive arginine
      vasopressin (ir-AVP) from rat hypothalami in vitro was examined. PC-PLC (0.05-01
      U ml-1) increased ir-AVP release but PI-PLC (0.01-0.5 U ml-1) did not. The
      response to a submaximal concentration of PC-PLC (0.075 U ml-1) was inhibited by
      the protei kinase C (PKC) inhibitor Ro 31-8220 (40 microM) and by removal of
      extracellular Ca2+ but was unaffected by the nitric oxide (NO) precursor L
      arginine (1 mM), the NO synthase inhibitor N omega-nitro-L-arginine benzyl ester
      (1 mM) and the phospholipase A2 (PLA2) inhibitors quinacrine (100 microM) and
      dexamethasone (1 microM). The results suggest that PC-PLC plays an important role
      in AVP secretion. The responses to PC-PLC appear to be mediated by PKC but not by
      changes in NO synthase or PLA2 activity.

PMID- 9175130
TI  - Brain regions supporting intentional and incidental memory: a PET study.
AB  - Regional brain activity associated with intentional and incidental memory
      retrieval was studied with PET. Previously studied and new words were presented
      in either an intentional or an incidental memory task. Type of task was crossed
      with an encoding manipulation ('deep' vs 'shallow') which varied the probability
      that studied items would be remembered. In both tasks, deeply encoded items were
      associated with greater activation in the left hippocampus than were items that
      had received shallow encoding, suggesting that the involvement of the hippocampus
      in memory retrieval is independent of whether remembering is intentional or
      incidental. Right prefrontal and bilateral parietal cortex were more activated
      during the international task than during the incidental task, irrespective of
      encoding condition. Thus, these regions play a more extensive role in memory
      retrieval when remembering is intentional.

PMID- 9175131
TI  - Downregulation of Na+ channel mRNA in olfactory bulb tufted cells following
      deafferentation.
AB  - Unilateral naris cauterization blocks odorant access to ipsilateral olfactory
      receptor cells and results in functional deafferentation of the olfactory bulb
      (OB). We used naris cauterization on postnatal day 2 (P2) to study the effects of
      deafferentation on the expression of Na+ channel subunits in OB. In situ
      hybridization at P18 showed that expression of Na+ channel alpha II and beta I
      mRNA was dramatically downregulated in tufted cells, while signals in mitral
      cells showed no detectable changes. Our observations suggest that during critical
      periods of development in some neurons, Na+ channel expression may be modulated
      by physiological activity. The differential response in the tufted and mitral
      cells may reflect varying degrees of dependence on afferent input or fundamental
      differences in cell properties.

PMID- 9175132
TI  - Phototransduction and calcium exchange along the length of the retinal rod outer
      segment.
AB  - The aim of this study was to investigate whether there are differences in calcium
      exchange between the ends of a retinal rod outer segment (OS) which could be
      correlated with the know differences of light responsiveness and which could
      explain the latter. We found that there is little, if any, difference in the
      exchange current density. However, the time constant of the exchange current
      decay after a saturating flash of light lengthened from base to tip and more
      calcium was extruded at the tip than the base of the OS. Our analysis of the
      results leads to the conclusion that there is little, if any, difference in free
      calcium concentration between the ends of the outer segment, but that there is a
      difference in the bound calcium and that this can explain the difference in light
      responsiveness along the length of the rod.

PMID- 9175133
TI  - The serotonin transporter gene and peer-rated neuroticism.
AB  - Polymorphisms in the serotonin transporter gene (5HTT) have been reported to be
      associated with neuroticism (emotionality) and with depression. A recent report
      of an association between 5HTT and neuroticism involved unselected samples and
      self-report questionnaires. We attempted to extend these findings using a
      selected extremes design and peer ratings. From a sample of 2085 individuals,
      each assessed on neuroticism by two independent peers, we selected 52 individuals
      from the top 5% and 54 individuals from the bottom 5%. No association was found
      for either a functional 44 bp insertion/deletion polymorphism in 5HTT regulatory
      sequence (5HTTLPR) or for a non-functional variable number tandem repeat 5HTT
      polymorphism.

PMID- 9175134
TI  - The seats of reason? An imaging study of deductive and inductive reasoning.
AB  - We carried out a neuroimaging study to test the neurophysiological predictions
      made by different cognitive models of reasoning. Ten normal volunteers performed
      deductive and inductive reasoning tasks while their regional cerebral blood flow
      pattern was recorded using [15O]H2O PET imaging. In the control condition
      subjects semantically comprehended sets of three sentences. In the deductive
      reasoning condition subjects determined whether the third sentence was entailed
      by the first two sentences. In the inductive reasoning condition subjects
      reported whether the third sentence was plausible given the first two sentences.
      The deduction condition resulted in activation of the left inferior frontal gyrus
      (Brodmann areas 45, 47). The induction condition resulted in activation of a
      large area comprised of the left medial frontal gyrus, the left cingulate gyrus,
      and the left superior frontal gyrus (Brodmann areas 8, 9, 24, 32). Induction was
      distinguished from deduction by the involvement of the medial aspect of the left
      superior frontal gyrus (Brodmann areas 8, 9). These results are consistent with
      cognitive models of reasoning that postulate different mechanisms for inductive
      and deductive reasoning and view deduction as a formal rule-based process.

PMID- 9175135
TI  - Interferon-gamma receptors in nociceptive pathways: role in neuropathic pain
      related behaviour.
AB  - Interferon-gamma receptor (IFN-gamma R) immunoreactivity was observed in the
      superficial dorsal horn and lateral spinal nucleus in rat and mouse spinal cord.
      Dorsal rhizotomies did not reduce immunoreactivity in the rat. IFN-gamma R
      distribution overlapped with nitric oxide synthase-1 immunoreactivity. In wild
      type mice, intrathecal injections of mouse IFN-gamma evoked biting behaviour,
      whereas mice with disruption of the functional gene for IFN-gamma R did not
      respond. Both types of mice had similar withdrawal thresholds to mechanical
      stimulation and reacted similarly to foot-pad carrageenan injections. In contrast
      to wild-type mice, IFN-gamma R knock-out mice did not show autotomy after sciatic
      nerve section. This study demonstrates a functional IFN-gamma R in spinal
      nociceptive pathways related to neuropathic pain.

PMID- 9175136
TI  - Electrophysiological brain activity and memory source monitoring.
AB  - To investigate brain mechanisms involved in identifying the origin of memories,
      event-related potentials (ERPs) were recorded as participants discriminated
      previously presented (old) from new items or identified their earlier source
      (picture, word, or new). Differences in ERPs between old-new recognition and
      source identification were focused at frontal sites. For source identification,
      prominent negative deflections at occipital or frontal sites occurred depending
      on encoding task. These results support a model in which memory attributes are
      distributed neocortically and the frontal lobes are critical for source
      monitoring.

PMID- 9175137
TI  - Persistent patterns of brain activity: an EEG coherence study of the positive
      effect of music on spatial-temporal reasoning.
AB  - Motivated by predictions from the structured trion model of the cortex,
      behavioral experiments have demonstrated a causal short-term enhancement of
      spatial-temporal reasoning in college students following exposure to a Mozart
      sonata, but not in control conditions. The coherence analysis of
      electroencephalogram (EEG) recordings is well suited to the neurophysiological
      investigation of this behavioral enhancement. Here we report the presence of
      right frontal and left temporo-parietal coherent activity induced by listening to
      Mozart which carried over into the spatial-temporal tasks in three of our seven
      subjects. This carry-over effect was compared to EEG coherence analysis of
      spatial-temporal-tasks after listening to text. We suggest that these EEG
      coherence results provide the beginnings of understanding of the
      neurophysiological basis of the causal enhancement of spatial-temporal reasoning
      by listening to specific music. The observed long-lasting coherent EEG pattern
      might be evidence for structured sequences in cortical dynamics which extend over
      minutes.

PMID- 9175138
TI  - Normal perfusion pressure breakthrough syndrome in giant arteriovenous
      malformations.
AB  - The treatment of large, high-flow cerebral arteriovenous malformations is one of
      the most difficult operations which neurosurgeons encounter because of the
      complex surgery and the post-operative effects on the brain. We have evaluated 10
      patients with large, high-flow AVMs who underwent surgical resection. Patients
      were investigated with contrast-enhanced computed tomography and magnetic
      resonance imaging, 1231-IMP single photon emission computed tomography (SPECT)
      studies of cerebral flow and cerebral vasodilatory function, intraoperative Laser
      Doppler flowmetry (4 or 10 patients), and conventional angiography. The volume of
      the arteriovenous malformation nidi ranged from 32.8 to 210.5 cc. SPECT imaging
      performed on the first post-operative day showed marked hyperperfusion in the
      brain tissue surrounding the resected nidus, and these regions were normal on
      images on the 7th post-operative day. Laser Doppler flowmetry showed sudden, and
      marked increase in CBF immediately following placement of temporary clips on the
      main feeding artery. Angiograms done on 7-14 days following surgery showed a
      stagnating artery, fragile vessel, and a prolonged circulation time. Our results
      indicate that pre- and post-operative SPECT study, especially a dynamic SPECT
      study done on the first post-operative day, was the most useful examination for
      ascertaining the post-operative normal perfusion pressure breakthrough.

PMID- 9175139
TI  - Upregulation of protein-tyrosine nitration in the anterior horn cells of
      amyotrophic lateral sclerosis.
AB  - Spinal cords of sporadic cases with amyotrophic lateral sclerosis (ALS) and
      normal controls were immunohistochemically examined using antibodies for
      nitrotyrosine (NT), Cu/Zn superoxide dismutase (SOD), and nitric oxide synthase
      (NOS) of brain, endothelial, and inducible forms. Immunoreactivity for NT was
      densely detected in the motor neurons of ALS while it was not or was only
      minimally detected in those of controls. The staining was also found in the axons
      of motor neurons of ALS, but was not found in the controls. In contrast, although
      immunoreactivity for Cu/Zn SOD of the motor neurons was dense in the motor
      neurons, it was not different between the ALS and controls. Immunoreactivities
      for bNOS and eNOS in the motor neurons of ALS were stronger than those of
      controls, and were also found in degenerated axons in the anterior horn of ALS.
      However, the immunoreactivity for inducible NOS was only minimally detected in
      the motor neurons of ALS and controls, and was not detected in the degenerated
      axons of ALS. These results suggest that nitration of protein-tyrosine residue is
      upregulated in motor neurons of the spinal cord of ALS with selective increases
      of brain NOS- and endothelial NOS-like immunoreactivities.

PMID- 9175140
TI  - Amyotrophic lateral sclerosis immunoglobulins are ineffective in altering calcium
      influx through presynaptic voltage-sensitive calcium channels.
AB  - Recent work has suggested that one factor in the etiology of the neuromuscular
      disease, amyotrophic lateral sclerosis (ALS), may be an autoimmune mechanism in
      which presynaptic voltage-sensitive calcium channels are an antigenic target. We
      have developed a fluorescence technique to measure rapid Ca2+ influx through
      presynaptic calcium channels in isolated nerve terminals (synaptosomes) from rat
      cerebral cortex. Depolarization of the synaptosomes by elevated external K+
      concentration caused a rapid increase in cytoplasmic Ca2+, as measured by a
      change in fluorescence of the Ca2+ chelating dye, Fura-2, which was loaded inside
      the synaptosomes. Pharmacological characterization suggests that the P- and Q
      subtypes of voltage-sensitive calcium channels mediate the majority of this Ca2+
      influx. The synaptosome preparation has been used as a model system to
      investigate the effects of IgG, purified from eight ALS patients, on presynaptic
      calcium channel function. IgG (1 microgram ml-1 to 1 mg ml-1) was preincubated
      with the synaptosomes prior to depolarization. IgG, from these eight ALS
      patients, had no systematic effects on presynaptic Ca2+ influx. Thus, using this
      system, we find no evidence for an effect of ALS IgG on the function of
      presynaptic calcium channels.

PMID- 9175141
TI  - Oscillations of cerebrospinal fluid pressure in nonhydrocephalic persons.
AB  - Spontaneous cerebrospinal fluid (CSF) pressure oscillations with a wavelength of
      0.5-2/min (B-waves) are used as a criterion for shunt insertion in hydrocephalic
      patients. We describe CSF pressure oscillations in two nonhydrocephalic patients
      with normal baseline CSF pressure. Intracranial pressure was recorded via a
      ventricular drainage in a 54-year-old male who had a lumber CSF leak after
      surgery for lumbar spinal stenosis and disc herniation after the leak was closed.
      In the second patient, a 42-year-old male, CSF pressure was monitored via a
      lumbar drainage which was placed for treatment of a subcutaneous CSF effusion
      after resection of a recurrent temporal meningioma. CSF pressure oscillations of
      a wavelength of 0.5-2/min were observed with a relative frequency of 50% (patient
      1) and 60% (patient 2) of the recorded time. Also longer waves were observed. Our
      data suggest that CSF pressure oscillations are not confined to hydrocephalic
      patients with raised intracranial pressure.

PMID- 9175142
TI  - Comparison of vasodilatory effect of carbon dioxide inhalation and intravenous
      acetazolamide on brain vasculature using positron emission tomography.
AB  - Carbon dioxide (CO2) and acetazolamide are increasingly being used as
      vasodilators to detect cerebrovascular reserve capacity in patients of chronic
      cerebrovascular disease. The functional cerebrovascular reserve or ability of
      cerebral vessels to lower their resistance in response to decrease in cerebral
      perfusion pressure is expressed as change in cerebral blood flow from baseline
      under a vasodilatory stimuli. Theoretically a vasodilator causing maximum
      vasodilation, and thereby expressing complete reserve capacity would be more
      suitable for such a purpose. We quantitatively compared the vasodilating effect
      of 5% CO2 inhalation and 1 g of intravenous acetazolamide by positron emission
      tomography. Cerebrovascular reserve was quantified in six patients with chronic
      cerebrovascular disease in the same sitting, using oxygen-15 labeled water
      (H2(15)O) positron emission tomography at rest, during 5% CO2 inhalation and
      after 1 g intravenous acetazolamide. A significant linear correlation in both
      nonlesion hemisphere (r = 0.701, p < 0.001) and in lesion hemisphere (r = 0.626,
      p < 0.005) was found between CO2 and acetazolamide for cerebrovascular reserve
      capacity. This correlation improved by considering cerebrovascular reserve per
      unit change in arterial carbon dioxide (r = 0.744, p < 0.001 in nonlesion
      hemisphere and r = 0.721, p < 0.001 in lesion hemisphere). The quantitative value
      of global reserve capacity was different by CO2 stimuli (5.2%) and acetazolamide
      (49.7%). Though a similar vasodilatory response is elicited by both vasodilators,
      acetazolamide seems to be more potent and therefore should be preferred to detect
      patients with exhausted cerebrovascular reserve capacity.

PMID- 9175143
TI  - Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes.
AB  - Malignant glioma remains one disease for which there is no curative therapy.
      Clearly there is a need to explore new and innovative approaches for their
      treatment. In this report, we review our preclinical trial of a new adoptive
      immunotherapy protocol using cytotoxic T lymphocytes (CTL) which had been
      sensitized to glioma in vivo and then activated and their number expanded ex vivo
      using compounds which enhance signal transduction. These glioma-sensitized
      lymphocytes, when introduced systemically into rats with either an intracerebral
      or intradermal glioma, eradicated or slowed the progression of their tumor. These
      results indicate for the first time that a reproducible and sustained eradication
      of a malignant glioma could be achieved by the adoptive transfer of tumor
      sensitized, ex vivo expanded CTL. A Phase I clinical trial is now underway to
      test the safety and potential efficacy of this immunotherapy in patients with
      recurrent malignant glioma.

PMID- 9175144
TI  - Light-microscopic study of insulin like growth factor II (IGF-II) and insulin
      like growth factor I receptor (IGF-I-R) in myopathy.
AB  - The insulin like growth factors (IGFs) are mitogenic peptides that can stimulate
      cell division and differentiation. In experimental studies it has been shown that
      there is local-production of IGFs and their mRNA in regenerating muscle. The
      effect of IGF-I and -II is mediated by a cell surface, membrane bound receptor
      (IGF-I-R). In addition, IGF-II has its own distinct type 2 receptor. But the role
      of IGF-II binding to the type 2 receptor is unclear, and it is now widely
      believed that the growth-promoting activities of IGF-II are also mediated via the
      IGF-I-R. So far, there is some knowledge about the regulation and effects of IGFs
      in muscle regeneration in vitro and in animal models in vivo. However, cell lines
      and in vitro experiments with myogenic precursors differ in some respects from
      human regenerating muscle in vivo. Thus, we performed our immunohistochemical
      study to investigate the potential role of IGF-II and IGF-I-R in regenerating
      human skeletal muscle in situ. To investigate the state of regeneration, neural
      cell adhesion molecule (N-CAM) and cytoskeletal protein vimentin serial sections
      were also performed. Light-microscopic evaluation showed that muscle fiber
      regeneration in inflammatory and dystrophic myopathy corresponds closely to IGF
      II and IGF-I-R immunoreactivity in muscle fibers. The coexpression of IGF-II and
      IGF-I-R in regenerating muscle fibers corroborates the assumption that in human
      skeletal muscle there is a trophic pathway concerning the synthesis and autocrine
      action of IGF-II via the IGF-I-R. In conclusion, in human skeletal muscle, in
      vivo, muscle fiber derived IGF-II probably is biologically active on the cell
      type of origin and may play an autocrine role in muscle regeneration via the IGF
      I-R.

PMID- 9175145
TI  - Growth-associated protein GAP-43 detection in the neuronal somata following
      middle cerebral artery occlusion in the rat.
AB  - We first detected growth-associated protein (GAP-43) immunoreactivity in the
      neuronal somata following middle cerebral artery occlusion in the rat. Four days
      after the middle cerebral artery occlusion, GAP-43 immunoreactivity was detected
      in some cortical neurons of the ischemic penumbra at the level of the
      hippocampus.

PMID- 9175146
TI  - Assessment of cerebral blood flow and metabolism in vertebrobasilar insufficiency
      with 133Xenon and 15O inhalation methods.
AB  - Assessment of hemodynamic parameters in patients who had transient basilar
      symptoms suggesting vertebrobasilar insufficiency requires a systematic and
      accurate detection of brainstem or cerebellar infarcts. Our aim was to detect
      with 133Xenon and 15O2 inhalation methods, a low flow state underlying
      vertebrobasilar insufficiency in a patient who had no impairment of
      cerebrovascular control related to infarction of brainstem or cerebellum. A woman
      with intermittent vertebrobasilar symptoms had an angiogram, magnetic resonance
      imaging and evaluation of hemodynamic parameters with vertebrobasilar circulation
      with 133Xenon inhalation and 15O inhalation methods MRI failed to show any border
      zone or territorial infarcts or degenerative disease. Angiographic study showed
      significant arterial lesion involving vertebrobasilar vessels. A decrease of
      blood flow within vertebrobasilar circulation was observed according to 133Xenon
      and 15O inhalation methods. These preliminary results support the view that
      significant arterial changes within the vertebrobasilar system might account for
      a low flow state. 15O2 inhalation method might be in agreement with a previous
      study performed in vertebrobasilar insufficiency with 133Xenon inhalation method.

PMID- 9175148
TI  - Finite element methods in the simulation and analysis of intracranial blood flow.
AB  - This paper presents an introduction to the use of finite element methods in the
      simulation and analysis of intracranial blood flow and lays the foundation for
      more detailed clinically oriented studies. An overview of finite element theory
      is provided and includes the formulation of both the continuous and discrete
      equations of viscous fluid flow. A discussion of appropriate assumptions and
      boundary conditions governing arterial blood flow is presented. Two-dimensional,
      rigid-walled models are developed for flow in a straight artery, a 90 degrees
      curved artery and a bifurcated artery. For each model, a description of the
      finite element mesh, numerical solution and computational results are presented.
      This paper is the first in a series which will detail computational analysis of
      the relationship between pressure, velocity development of intracranial aneurysms
      and therapeutic approaches to aneurysm management. The goals of this research are
      to investigate the fluid dynamics that arise as a result of pulsatile flow in the
      arteries of the circle of Willis, relate these hemodynamics to the formation of
      aneurysms, develop a computational understanding of the effects of various
      therapies on blood flow related to aneurysms, and to develop and utilize patient
      specific computer simulations for treatment planning.

PMID- 9175147
TI  - Changes in cerebral blood flow accompanied with reduction of blood pressure
      treatment in patients with hypertensive intracerebral hemorrhages.
AB  - Blood pressure usually is reduced in patients with hypertensive intracerebral
      hemorrhage for the prevention of the expansion of the hematoma and recurrent
      hemorrhage in acute stage. However, disturbed autoregulation of cerebral
      circulation is expected, and decreased cerebral blood flow (CBF) caused by
      excessive hypotension has been pointed out. There are different mechanisms of
      action in hypotensives, thereby the influence of hypotension on CBF in patients
      with the thalamic hemorrhage was investigated using nitroglycerin (TNG),
      diltiazem hydrochloride (DH) and trimethaphan camsilate (TC). Average CBF in a
      hemisphere on the hematoma side, the hemisphere without hematoma, and around the
      hematoma showed a slight decline after administration of TNG or DH. However, CBF
      declined more, after TC than DH. DH and TNG are preferable in descending order to
      control blood pressure of patients with intracerebral hemorrhage in the acute
      stages in view of a smaller decline in CBF.

PMID- 9175149
TI  - A new variant of progressive encephalomyelitis with rigidity associated with
      cerebellar ataxia and dementia: correlation of MRI and histopathological changes.
      A case report.
AB  - A 27 year-old patient developed a progressive neurological multisystem disorder.
      Initial signs were cerebellar ataxia and dementia, followed by rigidity and
      oculomotor dysfunction. Myoclonus was not present. MRI showed a marked atrophy of
      the spinal cord, the cerebellum, and mild (sub)cortical atrophy. CSF contained
      oligoclonal bands, but no anti-glutamic acid dehydrogenase antibodies. He died 33
      months after onset of symptoms. Autopsy revealed widespread neuropathological
      alterations including perivascular lymphocytic cutting, neuronal cell loss, and
      micro/astrogliosis the distribution of which corresponded to the changes seen in
      MRI. The diagnosis of progressive encephalomyelitis with rigidity was
      pathohistologically confirmed. Brain samples were negative for neurotrophic
      viruses tested by polymerase chain reaction. A new variant of this rare disorder
      is described initially presenting with ataxia and dementia, but without
      myoclonus.

PMID- 9175150
TI  - N omega-nitro-L-arginine attenuates early ischemic neuronal damage of prolonged
      focal cerebral ischemia and recirculation in rats.
AB  - The present study aimed to examine the effects of N omega-nitro-L-arginine (LNA)
      on the early ischemic neuronal damage (EIND). All the experiments were carried
      out under general anesthesia, maintaining the blood gases and the body
      temperature within the physiological ranges. The local CBF, the topographically
      corresponding cortical specific gravity, and the volume of EIND were determined
      in each rat, which was subjected to prolonged or temporary occlusion of middle
      cerebral artery (MCA) using our original miniclip. Significant cortical edema
      developed only in the brain area where the local CBF value was below 200 ml 100 g
      1 min-1. The prolonged MCA occlusion for 1, 2, and 4 h induced a time-dependent
      increase in the severity of cortical edema and the volume of EIND. Removal of the
      clip invariably induced recirculation. Compared to that induced by 4 h prolonged
      ischemia, the brain damage was improved by 1 h MCA occlusion followed by 3 h
      recirculation, whereas it was significantly worsened by 2 h ischemia followed by
      2 h recirculation. While LNA [1 mg, i.p., given two times during the experiment]
      only partially inhibited the activity of brain nitric oxide synthase, it
      remarkably ameliorated EIND of both prolonged ischemia and recirculation in this
      model. The above findings indicate the pathogenic role of nitric oxide in
      prolonged ischemia as well as recirculation.

PMID- 9175151
TI  - Effects of hyperosmolar mannitol on regional oxygen supply and consumption in the
      newborn pig.
AB  - Previous work indicated that opening the blood-brain barrier with hyperosmotic
      mannitol decreased local venous O2 saturation and increased cerebral O2
      consumption. This study was performed to assess the vascular effect of hypertonic
      mannitol on oxygen supply/consumption balance in the newborn pig and to determine
      the role of nitric oxide in mediating the effects of mannitol. Animals were
      anesthetized with alpha-chloralose and mechanically ventilated to maintain their
      blood gases within normal range. Retrograde catheterization of the right carotid
      artery was performed to inject 12 ml to 25% mannitol over a 30 sec interval. In
      one group of animals (n = 5), the blood-brain barrier transfer coefficient (Ki)
      to 14C-alpha aminoisobutyric acid or 14C-urea (n = 4) was measured 12 min after
      mannitol. In another group of animals (n = 9), regional cerebral blood flow and
      small vein O2 saturation was measured using 14C-iodoantripyrine and
      microspectrophotometry. Similar measurements were made in other groups of animals
      (n = 9) after pretreatment with 10 mg kg-1 i.v. of N-omega-nitro-L-arginine
      methyl ester (L-NAME), 20 min before mannitol injection. The mannitol injection
      did not increase Ki or local cerebral O2 consumption. It resulted in a decreased
      small vein O2 saturation in the ipsilateral cortex (46 +/- 3%) in comparison to
      the contralateral cortex (55 +/- 2%). The O2 supply/consumption ratio decreased
      in the ipsilateral cortex in the mannitol injected animals (2.14 +/- 0.23) in
      comparison to the contralateral cortex (2.76 +/- 0.28). Pretreatment with L-NAME
      abolished this effect of mannitol (small vein O2 saturation 59 +/- 2% in
      ipsilateral cortex and 58 +/- 2% in the contralateral cortex; O2
      supply/consumption 2.68 +/- 0.17 in the ipsilateral cortex and 2.65 +/- 0.16 in
      the contralateral cortex). We conclude that hypertonic mannitol adversely affects
      O2 supply/consumption balance, without increasing blood-brain barrier transport,
      and this effect is blocked by L-NAME, a nitric oxide synthase antagonist.

PMID- 9175152
TI  - Fasudil (HA1077), an intracellular calcium antagonist, improves neurological
      deficits and tissue potassium loss in focal cerebral ischemia in gerbils.
AB  - The effects of an intracellular calcium antagonist fasudil (HA 1077) on protein
      synthesis, ion derangement, brain edema, and the neurological signs associated
      with focal cerebral ischemia, were investigated via a nine-hour occlusion of the
      left common carotid artery (CCA) in Mongolian gerbils. Protein synthesis was
      evaluated by the amount of incorporation of [14C]methionine into the tissue.
      Intravenous infusion of fasudil hydrochloride (1 mg kg-1) just after CCA ligation
      was effective in reducing neurological deficits six and nine hours after CCA
      ligation, as well as loss of tissue potassium. However, fasudil did not
      ameliorate the brain edema or the accumulation of sodium in the tissue. On the
      other hand, fasudil improved the uptake of [14C]methionine, but not its
      incorporation into the tissue. The improved uptake of tracer into the tissue may
      indicate the facilitation of collateral blood flow by fasudil. These results
      suggest that fasudil may mitigate ischemic damage in the penumbral zone, possibly
      by ameliorating collateral blood flow and preventing calcium-related cell damage.

PMID- 9175153
TI  - Effect of high simple dose of cisplatinum and of radiation on the brain of
      rabbit.
AB  - In former studies of intracarotid and intravenous administration of cisplatinum,
      separate and combined with brain irradiation, we found no cerebral damage. In
      this study, gradually increasing high doses (above the therapeutic ones) of
      cisplatinum were administered intravenously to one series of rabbits and
      increasing high amounts of irradiation (above the therapeutic amounts) were given
      to another series. Although the rabbits that received highest doses of
      irradiation developed areas of alopecia and skin ulcers on the head, the general
      clinical and histopathologic examination of the rabbits' brains in both series
      was normal. The purpose of this study was to establish the effects of high doses
      of intravenous cisplatinum and irradiation on the rabbits brains.

PMID- 9175154
TI  - The use of high power drills for laminectomy in spinal stenosis: technical
      report.
AB  - High power drill systems are being used for cervical and lumbar spinal stenosis
      surgeries. The use and comparative analysis of several systems are presented.

PMID- 9175155
TI  - Tachykinins in the gut. Part I. Expression, release and motor function.
AB  - The preprotachykinin-A gene-derived peptides substance P and neurokinin (NK) A
      are expressed in distinct neural pathways of the mammalian gut. When released
      from intrinsic enteric or extrinsic primary afferent neurons, tachykinins have
      the potential to influence both nerve and muscle by way of interaction with three
      different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Most
      prominent among the effects of tachykinins is their excitatory action on
      gastrointestinal motor activity, which is seen in virtually all regions and
      layers of the mammalian gut. This action depends not only on a direct activation
      of the muscle through NK1 and/or NK2 receptors, but also on stimulation of
      excitatory enteric motor pathways through NK3 and/or NK1 receptors. In addition,
      tachykinins can inhibit motor activity by stimulating either inhibitory neuronal
      pathways or interrupting excitatory relays. A synopsis of the available data
      indicates that endogenous substance P and NKA interact with other enteric
      transmitters in the physiological control of gastrointestinal motor activity.
      Derangement of the regulatory roles of tachykinins may be a factor in the
      gastrointestinal dysmotility associated with infection, inflammation, stress and
      pain. In a therapeutic perspective, it would seem conceivable, therefore, that
      tachykinin agonists and antagonists are adjuncts to the treatment of motor
      disorders that involve pathological disturbances of the gastrointestinal
      tachykinin system.

PMID- 9175156
TI  - Tachykinins in the gut. Part II. Roles in neural excitation, secretion and
      inflammation.
AB  - The preprotachykinin-A gene-derived peptides substance (substance P; SP) and
      neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all
      layers of the gut, and extrinsic primary afferent nerve fibers, which innervate
      primarily the arterial vascular system. The actions of tachykinins on the
      digestive effector systems are mediated by three different types of tachykinin
      receptor, termed NK1, NK2 and NK3 receptors. Within the enteric nervous system,
      SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to
      modulate neuronal excitability via stimulation of NK3 and NK1 receptors. In the
      intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and
      it appears as if SP and NKA play a messenger role in intramural secretory reflex
      pathways. Secretory processes in the salivary glands and pancreas are likewise
      influenced by tachykinins. The gastrointestinal arterial system may be dilated or
      constricted by tachykinins, whereas constriction and an increase in the vascular
      permeability are the only effects seen in the venous system. Various
      gastrointestinal disorders are associated with distinct changes in the tachykinin
      system, and there is increasing evidence that tachykinins participate in the
      hypersecretory, vascular and immunological disturbances associated with infection
      and inflammatory bowel disease. In a therapeutic perspective, it would seem
      conceivable that tachykinin antagonists could be exploited as antidiarrheal,
      antiinflammatory and antinociceptive drugs.

PMID- 9175157
TI  - S-adenosylmethionine synthesis: molecular mechanisms and clinical implications.
AB  - Methionine adenosyltransferase (MAT) is an ubiquitous enzyme that catalyzes the
      synthesis of S-adenosylmethionine from methionine and ATP. In mammals, there are
      two genes coding for MAT, one expressed exclusively in the liver and a second
      enzyme present in all tissues. Molecular studies indicate that liver MAT exists
      in two forms: as a homodimer and as a homotetramer of the same oligomeric
      subunit. The liver-specific isoenzymes are inhibited in human liver cirrhosis,
      and this is the cause of the abnormal metabolism of methionine in these subjects.

PMID- 9175158
TI  - Thalamocortical synapses.
AB  - Thalamocortical synapses inform the cerebral neocortex about the external and
      internal worlds. The thalamus produces myriad thalamocortical pathways that vary
      in morphological, physiological, pharmacological and functional properties. All
      these features are of great importance for understanding how information is
      acquired, integrated, processed, stored and retrieved by the thalamocortical
      system. This paper reviews the properties of the afferents from thalamus to
      cortex, and identifies some of the gaps in our knowledge of thalamocortical
      pathways.

PMID- 9175159
TI  - The heat shock stress response after brain lesions: induction of 72 kDa heat
      shock protein (cell types involved, axonal transport, transcriptional regulation)
      and protein synthesis inhibition.
AB  - The cerebral stress response is examined following a variety of pathological
      conditions such as focal and global ischemia, administration of excitotoxins, and
      hyperthermia. Expression of 72 kDa heat shock protein (Hsp70) and hsp70 mRNA, the
      mechanism underlying induction of hsp70 mRNA involving activation of heat shock
      factor 1, and inhibition of cerebral protein synthesis are different aspects of
      the stress response considered here. The results are compared with those in the
      literature on induction, transcriptional regulation, expression, and cellular
      location of Hsp70, with a view to getting more insight into the function of the
      stress response in the injured brain. The present results illustrate that Hsp70
      can be expressed in cells affected at various degrees following an insult that
      will either survive or dic as the brain lesion develops, depending on the
      severity of cell injury. This indicates that, under certain circumstances,
      synthesized Hsp70 might be necessary but not sufficient to ensure cell survival.
      Other situations involve uncoupling between synthesis of hsp70 mRNA and protein,
      probably due to very strict protein synthesis blockade, and often result in cell
      loss. Cells eventually will die if protein synthesis rates do not go back to
      normal after a period of protein synthesis inhibition. The stress response is a
      dynamic event that is switched on in neural cells sensitive to a brain insult.
      The stress response is, however, tricky, as affected cells seem to need it, have
      to deal transiently with it, but eventually be able to get rid of it, in order to
      survive. Putative therapeutic treatments can act either selectively, potentiating
      the synthesis of Hsp70 protein and recovery of protein synthesis, or preventing
      the stress response by deadening the insult severity.

PMID- 9175160
TI  - Psychopharmacology of dopamine: the contribution of comparative studies in inbred
      strains of mice.
AB  - Comparative studies of behavioral responses to centrally acting drugs in inbred
      strains of mice which show differences in brain neurotransmitter activity
      represent a major strategy in the investigation of the neurochemical bases
      underlying behavioural expression. Moreover, these studies represent a
      preliminary stage in behavioral genetic research since they allow quantitative
      scales to be established and suggest correlations to be tested in recombinant
      inbred strains. The present review evaluates results obtained in mice of the
      C57BL/6 (C57) and DBA/2 (DBA) inbred strains which have been used for studies of
      the behavioral pharmacology of dopamine (DA) and investigated for the functional
      and anatomical characteristics of their brain DA systems. Differences between C57
      and DBA strain involve susceptibility and sensitivity as well as qualitative
      differences in the type or direction of the behavioral effects of DA agonists.
      Moreover, data on strain-dependent differences for DA metabolism, release and
      receptor densities and distribution provide important indications about the
      relationship between behavioral and central effects of DA agonists and, more
      generally, about the involvement of brain DA in behavior. Comparative studies in
      C57 and DBA mice have also revealed differences in susceptibility to context
      dependent, context-independent and stress-induced behavioral sensitization to
      psychostimulants. Consequently, they support the view that the term "behavioral
      sensitization" may define different phenomena in which different, independent
      genotype-related factors play a major role. Finally, studies on the behavioral
      and central effects of stressful experiences in C57 and DBA mice together with
      psychopharmacogenetic analyses, indicate that different symptomatological
      profiles may derive from genotype-dependent adaptation of brain DA receptors to
      environmental pressure.

PMID- 9175161
TI  - The fimbria-fornix/cingular bundle pathways: a review of neurochemical and
      behavioural approaches using lesions and transplantation techniques.
AB  - Extensive lesions of the fimbria-fornix pathways and the cingular bundle deprive
      the hippocampus of a substantial part of its cholinergic, noradrenergic and
      serotonergic afferents and, among several other behavioural alterations, induce
      lasting impairment of spatial learning and memory capabilities. After a brief
      presentation of the neuroanatomical organization of the hippocampus and the
      connections relevant to the topic of this article, studies which have contributed
      to characterize the neurochemical and behavioural aspects of the fimbria-fornix
      lesion "syndrome" with lesion techniques differing by the extent, the location or
      the specificity of the damage produced, are reviewed. Furthermore, several
      compensatory changes that may occur as a reaction to hippocampal denervation
      (sprouting changes in receptor sensitivity and modifications of neurotransmitter
      turnover in spared fibres) are described and discussed in relation with their
      capacity (or incapacity) to foster recovery from the lesion-induced deficits.
      According to this background, experiments using intrahippocampal or
      "parahippocampal" grafts to substitute for missing cholinergic, noradrenergic or
      serotonergic afferents are considered according to whether the reported findings
      concern neurochemical and/or behavioural effects. Taken together, these
      experiments suggest that appropriately chosen fetal neurons (or other cells such
      as for instance, genetically-modified fibroblasts) implanted into or close to the
      denervated hippocampus may substitute, at least partially, for missing
      hippocampal afferents with a neurochemical specificity that closely depends on
      the neurochemical identity of the grafted neurons. Thereby, such grafts are able
      not only to restore some functions as they can be detected locally, namely within
      the hippocampus, but also to attenuate some of the behavioural (and other types
      of) disturbances resulting from the lesions. In some respects, also these graft
      induced behavioural effects might be considered as occurring with a
      neurochemically-defined specificity. Nevertheless, if a graft-induced recovery of
      neurochemical markers in the hippocampus seems to be a prerequisite for also
      behavioural recovery to be observed, this neurochemical recovery is neither the
      one and only condition for behavioural effects to be expressed, nor is it the one
      and only mechanism to account for the latter effects.

PMID- 9175162
TI  - Using computer technology for health education.

PMID- 9175163
TI  - Children on the radio! An exciting programme in Mozambique.

PMID- 9175164
TI  - Preserving our vitality: strategies for personal and professional growth.
AB  - How then can we stay renewed in our work? How best to manage the stresses that
      diminish our vitality? Establish priorities. Find creative solutions to
      organisational dilemmas. Manage conflicts skillfully. Give support to one another
      and protect your health. For if you do these things, your work will have new
      meaning, and that which is important will be rediscovered by you-and everyone you
      meet on your journey.

PMID- 9175165
TI  - The prevention of substance abuse in schools: a process evaluation of the
      adoption of a standardised education module.

PMID- 9175166
TI  - Health education in Latin America: the difficulties of community participation
      and empowerment.

PMID- 9175167
TI  - A model for making AIDS training accessible to health professionals in Puerto
      Rico.

PMID- 9175168
TI  - Education cannot do it alone: new partnerships for new paradigms. International
      Seminar on Ergonomics and Work.

PMID- 9175169
TI  - Effects of dietary supplementation with arachidonic acid rich oils on nerve
      conduction and blood flow in streptozotocin-diabetic rats.
AB  - Diabetes mellitus is associated with defective essential fatty acid desaturation.
      In experimental models this contributes to characteristic reductions in
      peripheral nerve conduction velocity (NCV) and blood flow, which may be corrected
      by dietary supplementation with gamma-linolenic acid (GLA) rich oils to bypass
      the delta-6 desaturation deficit. There is debate about the mechanism of this
      improvement, including whether it depends on synthesis of series 1 prostanoids
      derived from di-homo GLA or series 2 prostanoids from arachidonic acid (ARA). The
      aim was to assess the efficacy of two ARA-rich (approximately 39% content) oils
      in correcting neurovascular dysfunction in streptozotocin-induced diabetic rats.
      After 6 weeks of untreated diabetes, rats were treated for a further 2 weeks with
      1% dietary oil supplements before assessment of sciatic motor NCV and endoneurial
      blood flow. NCV was 19% reduced in diabetic rats and this was largely
      (approximately 86%) corrected by both oil treatments. A 48% deficit in
      endoneurial nutritive blood flow with diabetes was approximately 70% reversed by
      the two oils, vascular conductance being in the non-diabetic range. Thus, nerve
      conduction and perfusion deficits in diabetic rats are corrected by ARA-rich oil
      treatment. The magnitudes of these changes were similar to expectations based on
      previous studies of GLA-rich oils, therefore it is likely that the neurovascular
      effect of increased synthesis of series 2 prostanoids makes a major contribution
      to the beneficial action of n-6 essential fatty acids in experimental diabetic
      neuropathy.

PMID- 9175170
TI  - Endothelial cell monolayer dysfunction caused by oxidized low density
      lipoprotein: attenuation by oleic acid.
AB  - Oleic acid (18:1) may exert beneficial effects on the pathogenesis of vascular
      disease by a variety of mechanisms. To determine if 18:1 exerts direct protective
      effects on vascular endothelial cells, porcine pulmonary artery endothelial cells
      (PAEC) were supplemented with 0.1 mM 18:1, gamma-linolenic acid (18:3), or
      ethanol vehicle (ETOH) prior to treatment with low density lipoprotein (LDL), or
      CU(2+)-oxidized LDL (OXLDL). Treatment with neither LDL nor OXLDL (100 micrograms
      protein/ml) for 24-48 h caused PAEC cytotoxicity, whereas OXLDL, but not LDL,
      caused derangements in PAEC actin microfilament architecture and monolayer
      barrier dysfunction. Supplementation with 18:1, but not 18:3, attenuated
      derangements caused by OXLDL and lysophosphatidylcholine, a component of OXLDL.
      These results demonstrate that monounsaturated fatty acids directly alter the
      response of vascular endothelial cells to OXLDL and may retard the
      atherosclerotic process by decreasing the efflux of macromolecules (e.g. LDL)
      into the vessel wall.

PMID- 9175171
TI  - Modulation of prostaglandin production by nitric oxide in astroglia.
AB  - We examined the effects of exogenous nitric oxide (NO) on prostaglandin
      production in fetal ovine astroglia. Astroglia in secondary culture grown in 12
      well plates were exposed to medium alone or medium containing 10 ng/ml
      interleukin 1 alpha (IL1 alpha), in the presence or absence of 10 and 100 microM
      sodium nitroprusside (SNP). Sodium nitroprusside is a NO donor. Prostaglandin F2
      alpha (PGF2 alpha) levels were determined by enzyme immunoassay after 4 h of
      medium and/or drug application. Application of 100 microM SNP reduced basal
      levels of PGF2 alpha from 530 +/- 48 pg/ml (mean +/- SEM) (n = 9) to 248 +/- 60
      pg/ml (n = 8) (P < 0.05). In IL1 alpha treated cells, PGF2 alpha levels were 846
      +/- 109 pg/ml (n = 9) (P < 0.05, compared to basal levels) in the absence and 567
      +/- 122 pg/ml (n = 9) in the presence of 100 microM SNP (P < 0.05, compared to
      IL1 alpha alone). We tested whether effects of exogenous NO on PGF2 alpha levels
      would be influenced by elimination of endogenously produced NO. Inhibition of NO
      synthase with 100 microM NG-nitro-L-arginine-methyl ester (L-NAME) did not affect
      PGF2 alpha levels during basal conditions, or affect reductions in PGF2 alpha
      levels during application of 100 microM SNP. In addition, L-NAME application did
      not affect IL1 alpha-induced increase in PGF2 alpha levels or reductions in PGF2
      alpha levels with coapplication of 100 microM SNP. In contrast to the higher
      dose, application of 10 microM did not significantly affect PGF2 alpha levels. In
      summary, application of 100 microM SNP reduces basal production of PGF2 alpha and
      attenuates increases in PGF2 alpha levels with IL1 alpha application.

PMID- 9175172
TI  - Expression of recombinant human cyclooxygenase isoenzymes in transfected COS-7
      cells in vitro and inhibition by tenoxicam, indomethacin and aspirin.
AB  - The recent discovery of cyclooxygenase-2 (COX-2), an isoenzyme associated mainly
      with inflammation created the need to reevaluate cyclooxygenase inhibitors with
      reliable screening methods. In the present study we standardized a technique to
      determine the IC50S of cyclooxygenase inhibitors on recombinant human COX-1 and
      COX-2 expressed in mammalian cells and used it to study the compounds tenoxicam,
      aspirin and indomethacin. The IC50S of aspirin, indomethacin and tenoxicam for
      human COX-1 were 0.41 +/- 0.07 microgram/ml, 0.008 +/- 0.003 microgram/ml, and
      7.94 +/- 3.28 micrograms/ml, respectively, and for human COX-20.64 +/- 0.16
      microgram/ml, 0.09 +/- 0.05 microgram/ml, and 10.61 +/- 1.50 micrograms/ml, for
      aspirin, indomethacin, and tenoxicam. Tenoxicam had the lowest IC50hCOX
      2/IC50hCOX-1 ratio (1.34), followed by aspirin (1.53) and indomethacin (10.82).
      The system described in the present study provides a simple and efficient way to
      determine the specificity of NSAID inhibition for each of the human
      cyclooxygenase isoenzymes separately.

PMID- 9175173
TI  - Percutaneous transluminal angioplasty increases thromboxane A2 production in
      claudicants.
AB  - Percutaneous transluminal angioplasty is an acute, local stimulus to platelets
      which activation is regarded as an important factor for a later restenosis. The
      balance between the production of prostacyclin and thromboxane A2 is of
      (patho)physiological importance due to their opposite actions on vascular tone
      and platelet reactivity. In this study we investigated the influence of
      percutaneous transluminal angioplasty of the peripheral arteries on prostacyclin
      and thromboxane A2 productions in vivo by measuring the excretions of their
      urinary index metabolites, 2,3-dinor-6-ketoprostaglandin F1 alpha and 11
      dehydrothromboxane B2, respectively, in 10 patients. We found a twofold increase
      in thromboxane A2, but no significant change in prostacyclin, production after
      peripheral transluminal angioplasty which shifted prostacyclin/thromboxane A2
      balance to the direction of thromboxane A2 formation. This gives theoretical
      support to the use of thromboxane A2 synthase inhibitors and receptor antagonists
      as well as prostacyclin analogues in combination with peripheral percutaneous
      transluminal angioplasty to prevent thrombosis and restenosis.

PMID- 9175174
TI  - Effect of azelastine hydrochloride on release and production of platelet
      activating factor in human neutrophils.
AB  - Effect of azelastine hydrochloride (azelastine) on release and production of
      platelet-activating factor (PAF) in neutrophils obtained from asthmatic and non
      asthmatic patients was investigated. Neutrophils were preincubated with or
      without azelastine and stimulated with f-Met-Leu-Phe (fMLP, 10 microM) for 15
      min. PAF-like activity was detected by aggregation of washed guinea pig
      platelets. PAF-like activity released from asthmatic neutrophils without
      preincubation of azelastine was 5.67[0.89] (mean[SD], ng/10(7) cells) in
      supernatants and 21.8[0.76] in cell pellets. After preincubation with 10(-8), 10(
      6), and 10(-4) M of azelastine, PAF-like activity reduced to 5.96[0.97]
      (mean[SD], ng/10(7) cells), 3.49[0.63], and 1.89[0.09] (n = 15) in the
      supernatants, and 20.7[0.97], 13.9[0.29], and 8.91 [0.99] (n = 15) in the cell
      pellets, respectively. PAF-like activity in non-asthmatic neutrophils without
      preincubation of azelastine was 4.67[0.19] (mean[SD], ng/10(7) cells) in
      supernatants and 18.5[0.34] in cell pellets. After preincubation with 10(-8), 10(
      6), and 10(-4) M of azelastine, PAF-like activity reduced to 4.39[0.51]
      (mean[SD], ng/10(7) cells), 2.77[0.22], and 1.75[0.07] (n = 15) in the
      supernatants, and 17.9[0.54], 10.8[0.25], and 5.97 [0.59] (n = 15) in the cell
      pellets, respectively. Our results showed that preincubation with azelastine
      caused a dose-dependent inhibition of intra and extracellular PAF-like activity
      from asthmatic and non-asthmatic neutrophils in the same manner.

PMID- 9175176
TI  - Chloroquine minimizes sampling artefacts for radioimmunological determination of
      thromboxane B2 in plasma.
AB  - Chloroquine is known to inhibit platelet activation by various mechanisms
      including arachidonic acid liberation from membrane phospholipids. We therefore
      examined the influence of chloroquine in addition to the conventional
      EDTA/acetylsalicylic acid cocktail on thromboxane B2-plasma values. In 11 healthy
      volunteers the influence of venous occlusion, needle diameter and EDTA (+
      acetylsalicylic acid + chloroquine) was examined. In 27 healthy adults, 51
      patients with clinically manifested coronary heart disease as well as in 31
      patients with peripheral vascular disease parallel samples drawn in the presence
      of chloroquine showed lower thromboxane B2 in all these three groups of patients,
      especially in conditions associated with platelet activation and high thromboxane
      B2-values. These findings suggest that the routine addition of 10 mM chloroquine
      to the conventional stabilization cocktail can strongly be recommended.

PMID- 9175175
TI  - Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella
      foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in
      patients with coronary artery disease.
AB  - In a placebo-controlled study the effect of ginger and fenugreek was examined on
      blood lipids, blood sugar, platelet aggregation, fibrinogen and fibrinolytic
      activity. The subjects included in this study were healthy individuals, patients
      with coronary artery disease (CAD), and patients with non-insulin-dependent
      diabetes mellitus (NIDDM) who either had CAD or were without CAD. In patients
      with CAD powdered ginger administered in a dose of 4 g daily for 3 months did not
      affect ADP- and epinephrine-induced platelet aggregation. Also, no change in the
      fibrinolytic activity and fibrinogen level was observed. However, a single dose
      of 10 g powdered ginger administered to CAD patients produced a significant
      reduction in platelet aggregation induced by the two agonists. Ginger did not
      affect the blood lipids and blood sugar. Fenugreek given in a dose of 2.5 g twice
      daily for 3 months to healthy individuals did not affect the blood lipids and
      blood sugar (fasting and post prandial). However, administered in the same daily
      dose for the same duration to CAD patients also with NIDDM, fenugreek decreased
      significantly the blood lipids (total cholesterol and triglycerides) without
      affecting the HDL-c. When administered in the same daily dose to NIDDM (non-CAD)
      patients (mild cases), fenugreek reduced significantly the blood sugar (fasting
      and post prandial). In severe NIDDM cases, blood sugar (both fasting and post
      prandial) was only slightly reduced. The changes were not significant. Fenugreek
      administration did not affect platelet aggregation, fibrinolytic activity and
      fibrinogen.

PMID- 9175177
TI  - Pharmacokinetics and pharmacodynamics of intra-graft iloprost in femorodistal
      bypass surgery.
AB  - Intra-graft injection of the prostacyclin analogue, iloprost, was performed at
      the end of femorodistal bypass procedures in 12 patients with severe peripheral
      arterial occlusive disease. Iloprost plasma levels were measured and compared
      with changes in haemodynamics. There was a high initial iloprost plasma level
      (mean 625 pg/ml) which dropped to a mean of 50 pg/ml after 15 min. This
      correlated with an immediate reduction in systolic blood pressure which had
      returned to pretreatment levels after 15 min. In contrast, the vascular
      resistance distal to the graft showed a reduction after 5 min which was
      maintained for at least 20 min after iloprost injection and the mean blood flow
      through the graft increased steadily throughout the same period of measurement.
      The study showed an effect of iloprost on blood pressure which correlated with
      plasma levels, but the time course of the changes in distal vascular resistance
      and graft blood flow demonstrated an effect more prolonged than the half-life of
      iloprost.

PMID- 9175178
TI  - Essential fatty acid status in plasma phospholipids of mother and neonate after
      multiple pregnancy.
AB  - During singleton pregnancy, maternal essential fatty acid (EFA) status decreases
      progressively. After multiple pregnancy it can be expected that the neonatal and
      maternal EFA status is even lower. To study whether the maternal EFA supply to
      the fetus is a limiting factor to the neonatal EFA status, we compared the plasma
      phospholipid EFA status of newborn multiplets (30 pairs of twins and 7 sets of
      triplets) with that of singletons (n = 89) at birth and that of their mothers at
      delivery. After correction for gestational age, a slightly lower EFA status was
      found in maternal and umbilical plasma from multiplets compared to singletons. No
      relation was found between the difference in birthweight of the smallest and the
      largest neonate of a set of multiplets and the difference in cord plasma EFA
      levels. Correlations between maternal and umbilical plasma EFA levels were
      comparable for multiple and singleton pregnancies. Therefore, adequate dietary
      intake is required to guarantee an optimal neonatal EFA status, especially during
      multiple pregnancy.

PMID- 9175179
TI  - Prostaglandin production by guinea-pig endometrial cells: effects of caffeine and
      other modulators of intracellular calcium.
AB  - The glandular epithelial cells were found to be the main source of PGF2 alpha
      (the uterine luteolytic hormone) in guinea-pig endometrium. There was a selective
      increase in PGF2 alpha production by these cells in culture at the time of the
      cycle (i.e. day 15) at which there is increased PGF2 alpha release from the
      guinea-pig uterus in vivo. TMB-8 (an intracellular calcium antagonist), W-7,
      trifluoperazine (both calmodulin antagonists), thapsigargin (an inhibitor of
      intracellular calcium uptake) and berberine (an inhibitor of calcium release)
      reduced the output of PGF2 alpha from day 7 glandular epithelial cells indicating
      that intracellular calcium is necessary for PGF2 alpha production by these cells.
      In contrast to its stimulatory effect on PGF2 alpha output from the guinea-pig
      uterus superfused in vitro and guinea-pig endometrium in culture, caffeine
      inhibited the output of PGF2 alpha from guinea-pig glandular epithelial cells in
      culture. Its effect was not fully shared by theophylline, nor mimicked by
      forskolin showing that cyclic AMP is not involved. The inhibitory actions of
      caffeine and those of the compounds which interfere with the action of
      intracellular calcium were not additive, suggesting that caffeine modulates the
      action of intracellular calcium in some way. Caffeine reduced the intracellular
      free calcium concentration in endometrial cells, but it was not particularly
      effective in this respect on day 7 glandular epithelial cells. Caffeine may
      therefore modulate the action of intracellular calcium in some other way.

PMID- 9175180
TI  - Opportunities in managed care.

PMID- 9175181
TI  - Advantages of separating the triage function from the psychiatric emergency
      service.

PMID- 9175182
TI  - The political and moral economy of mental health.

PMID- 9175183
TI  - "It's a brain disease".

PMID- 9175184
TI  - Travel distance to subspecialty and general mental health services.

PMID- 9175185
TI  - Telemedicine and geriatric psychiatry.

PMID- 9175186
TI  - Disability payments and chemical dependence: conflicting values and uncertain
      effects.
AB  - Receipt of public support payments by people with substance abuse disorders has
      been a subject of intense controversy in recent years. Observing that such funds
      are often used to purchase addictive substances, many critics have questioned
      whether people with chemical dependencies are entitled to such payments and
      whether they should be allowed to spend these funds unsupervised. This discussion
      introduces a special section of five data-based papers on the relation of
      disability payments to chemical dependence. The papers address five questions: Do
      public support payments worsen substance abuse in vulnerable populations? Does
      assignment of a representative payee reduce substance abuse among such
      beneficiaries? What money management procedures are most likely to yield positive
      outcomes for clients? How can clients who need payees be fairly identified? And
      how should skilled, responsible payees or guardians be recruited, trained, and
      retained? In the absence of scientific data, both clinical practice and social
      policy are vulnerable to the whims of public opinion. These papers shed new light
      on a heated area of policy debate.

PMID- 9175187
TI  - The relationship of public support payments to substance abuse among homeless
      veterans with mental illness.
AB  - OBJECTIVE: A suspicion that disability payments may exacerbate substance use
      among persons with chemical addictions recently led Congress to limit federal
      disability entitlements of applicants whose disability status is related to
      substance abuse, even if they have another serious mental disorder. This study
      empirically explored the relationship between receipt of disability payments and
      substance use among homeless mentally ill veterans. METHODS: The study sample
      included 2,474 homeless veterans with a current diagnosis of schizophrenia and a
      substance abuse or dependence disorder who were assessed in a community outreach
      program sponsored by the Department of Veterans Affairs. RESULTS: After
      adjustment for other relevant factors, receipt of disability payments showed no
      significant relationship to the number of days of substance use a month, even
      among frequent users of alcohol and drugs. CONCLUSIONS: Findings about substance
      use among the homeless veterans with serious mental disorders in this study
      provide no support for the assertion that disability payments exacerbate
      substance use.

PMID- 9175188
TI  - Influence of retroactive disability payments on recipients' compliance with
      substance abuse treatment.
AB  - OBJECTIVE: This study examined whether substance abusers who received large
      retroactive payments from Social Security disability programs were more likely to
      terminate residential treatment precipitously than those who did not receive
      payments. METHODS: The records of 43 patients of a long-term residential
      treatment facility who received disability payments at some point during their
      treatment stay were blindly examined. Twenty-six of these patients received a
      large one-time retroactive payment representing money that accumulated during
      processing of the claims. To test the hypothesis that receipt of such a payment
      would lead to precipitous discharge, a survival regression model was used. A
      control group of nonrecipient patients was sampled at a comparable point in
      treatment. RESULTS: Subjects in the recipient group were significantly more
      likely to have unplanned discharges than those in the comparison group.
      CONCLUSIONS: These preliminary data suggest that large cash infusions can be
      disruptive to the course of treatment for substance abusers.

PMID- 9175189
TI  - Impact of representative payees on substance use by homeless persons with serious
      mental illness.
AB  - OBJECTIVE: Assignment of representative payees, third parties responsible for
      managing clients' funds, has been proposed to counter potential use of public
      support payments for abused substances by people with severe mental illness and
      substance use disorders. This study examines substance use outcomes in a sample
      of homeless persons with serious mental illness and substance use disorders, some
      of whom were assigned representative payees. METHODS: The subjects were
      participating in the Access to Community Care and Effective Services and Supports
      (ACCESS) program, a federally funded demonstration program on integrating service
      systems. Clients were assessed at baseline and three months after case management
      services were initiated. Factorial repeated-measures analysis of covariance was
      used to examine substance use among four client subgroups, two of which had
      payees and two of which did not. RESULTS: Clients in this sample (N = 1,348)
      showed significant improvement on all measures of substance use over the first
      three months in the program. Those with payees showed no greater improvement in
      substance abuse than those without payees, although they did have fewer days of
      homelessness. CONCLUSIONS: This study failed to find evidence that merely adding
      external money management services to existing services improves substance abuse
      outcomes among clients who had dual diagnoses and were homeless. Besides
      assigning a payee, structured behavioral interventions may be needed to produce
      additional clinical benefits.

PMID- 9175190
TI  - Monetary reinforcement of abstinence from cocaine among mentally ill patients
      with cocaine dependence.
AB  - OBJECTIVE: The study investigated whether contingency management could reduce
      cocaine use by patients with schizophrenia. METHODS: An A-B-A research design,
      with two-month baseline, intervention, and follow-up phases, was used to study
      two homeless, treatment-resistant male outpatients with DSM-III-R diagnoses of
      schizophrenia and cocaine dependence. During the intervention phase, subjects
      provided daily urine specimens for testing for the cocaine metabolite
      benzoylecgonine (BE) and received $25 for each negative test. Concentrations of
      BE and metabolites of other illicit drugs were assayed twice a week to determine
      the amount of drug use in addition to frequency. Analysis of variance was used to
      compare drug use during the three study phases. RESULTS: During the intervention,
      the proportion of tests positive for cocaine was lower for both subjects. Mean
      urinary concentrations of BE were significantly lower during the intervention
      than during the baseline. CONCLUSIONS: These results suggest that modest monetary
      reinforcement of abstinence may decrease cocaine use among cocaine-dependent
      patients with schizophrenia.

PMID- 9175191
TI  - Representative payee practices of community mental health centers in Washington
      State.
AB  - OBJECTIVE: A survey was conducted to evaluate the representative payee practices
      of community mental health centers (CMHCs) in Washington State, with emphasis on
      whether and how benefit disbursement practices were linked to patients' clinical
      behaviors, especially substance use. METHODS: A survey was pilot tested with
      several clinicians and sent to all 80 licensed CMHCs in Washington State. Data
      were analyzed using t tests, Pearson r correlations, and regression analysis.
      RESULTS: Of 41 responding agencies, 30 (73 percent) reported providing payee
      services for at least some of their patients, approximately one-third of whom had
      a dual diagnosis of a mental illness plus an alcohol or drug disorder. The
      frequency of benefit disbursement, but not the overall amount of funds disbursed,
      was moderately to highly linked by contingency management to patients' money
      management skills, substance use, and level of functioning; it was less tightly
      linked to treatment attendance. Larger and more experienced programs reported
      tighter linkage between benefit disbursement frequency and patients' behavior
      than did smaller programs. Responses also indicated a significant need for more
      clearly articulated guidelines for payee benefit management. CONCLUSIONS: Despite
      a lack of studies demonstrating the effectiveness of representative payee
      practices, CMHCs appear to be using contingency techniques to link benefit
      disbursement to clinical behaviors. Further studies of these practices, their
      outcomes, and associated ethical issues are needed.

PMID- 9175192
TI  - Clinical utility and patient acceptance of the computerized Composite
      International Diagnostic Interview.
AB  - OBJECTIVE: The study evaluated the utility to clinicians and the acceptability to
      patients of the self-administered computerized version of the Composite
      International Diagnostic Interview (CIDI-Auto) in an acute psychiatric setting.
      METHODS: Patients admitted to an acute psychiatric unit completed the CIDI-Auto.
      Reports of CIDI-Auto diagnoses and symptoms were given to treating psychiatrists,
      who completed a questionnaire evaluating the accuracy and usefulness of the
      reports. Patients answered a questionnaire about their attitudes toward computers
      before completing the CIDI-Auto, and after completing it, they answered a
      questionnaire about their reactions to the interview. RESULTS: Psychiatrists
      agreed with only 50 percent of CIDI-Auto current diagnoses and indicated that
      only 22 percent of CIDI-Auto reports provided useful new diagnoses, although 63
      percent helped to clarify diagnoses and 58 percent could save clinicians some
      time. They endorsed the CIDI-Auto as a possible aid to indirect or remote
      diagnosis where histories would be taken by nonexpert staff. Ninety-four percent
      of patients liked the computerized interview, and 83 percent understood the
      questions without difficulty. Sixty percent felt more comfortable with the
      computerized interview than with a doctor. Education and previous computer
      experience promoted positive attitudes and satisfaction with the computerized
      interview. CONCLUSIONS: Psychiatrists considered the current CIDI-Auto completed
      by patients to be of limited value in diagnosis and history taking. Despite
      patients' acceptance and positive reactions to the computer interview,
      satisfactory computerized diagnosis is yet to be attained.

PMID- 9175193
TI  - Management for quality: continuous quality improvement to increase access to
      outpatient mental health services.
AB  - OBJECTIVE: A health maintenance organization (HMO) examined whether continuous
      quality improvement could be used to address the problem of long waiting times
      for outpatient mental health services from a closed panel of providers during
      peak periods of demand. METHODS: A task force at a staff model HMO in Burlington,
      Vermont, used continuous quality improvement methods to identify and solve
      specific service access problems in five categories: quality, protocol, and
      standards; systems and processes; management and administration; clinical
      practice management; and public relations and marketing. RESULTS: Over a two-year
      period, the task force identified 13 specific problems, for which solutions were
      implemented. For example, two new support positions were created to meet
      clinicians' needs. Triage categories were defined, and acceptable waiting times
      for appointments, along with goals for percent compliance, were established. A
      weekly training program in brief psychotherapy and an extensive group
      psychotherapy program were implemented. A network of community providers was
      formed to complement the HMO's fixed provider panel during periods of high
      demand. The average waiting time was reduced from 22 days to six days, and
      patients' satisfaction increased markedly. CONCLUSIONS: Use of continuous quality
      improvement can guide clinical leaders in their central role of reinstating
      clinical quality as the goal of management. The author suggests that continuous
      quality improvement with balanced clinical and administrative leadership is the
      means to forge the needed synthesis of quality and cost capable of improving
      mental health.

PMID- 9175194
TI  - Factors influencing utilization of mental health and substance abuse services by
      American Indian men and women.
AB  - OBJECTIVE: This study investigated the effects of gender, number of lifetime
      psychiatric diagnoses, and childhood victimization on utilization of mental
      health and substance abuse treatment services in a Southwestern American Indian
      tribe. METHODS: A total of 582 individuals were recruited based on tribal
      enrollment and membership in large multigenerational pedigrees. Subjects were
      interviewed using a modified version of the Schedule for Affective Disorders and
      Schizophrenia-Lifetime Version, a semistructured psychiatric interview. For this
      study the definition of childhood victimization was limited to childhood sexual
      abuse. RESULTS: Fifty-six percent of the subjects had received mental health
      treatment, substance abuse treatment, or both. Patterns of service utilization
      differed by gender with the odds of inpatient and substance abuse treatment
      higher for men than for women. Women were more likely than men to receive mental
      health treatment. Subjects who had been sexually abused as children were more
      likely to have three or more psychiatric diagnoses and to have received extensive
      treatment, compared with subjects who reported no childhood sexual abuse history.
      Logistic regression demonstrated strong relationships between number of
      psychiatric diagnoses and the likelihood of treatment among both men and women.
      CONCLUSIONS: Gender, number of psychiatric diagnoses, and childhood sexual abuse
      are strong predictors of utilization of mental health and substance abuse
      treatment services. These factors should be considered in designing treatment
      interventions.

PMID- 9175195
TI  - Tuberculosis infection among people with severe mental illness.
AB  - In a study of the prevalence of tuberculosis infection and risk factors for
      infection among people with severe mental illness, 71 participants in a
      psychiatric day program were given a tuberculin skin test. Twelve of the 71
      subjects (17 percent) had positive results. None had active tuberculosis. Those
      with tuberculosis infection were more likely to be immigrants and to be above the
      study group's median age of 32. Eleven of the 12 infected subjects had
      experienced at least one of seven risk factors for tuberculosis infection, which
      suggests that more clinical attention should be placed on tuberculosis infection
      in this population.

PMID- 9175196
TI  - Psychiatrists' responses to failure of maintenance therapy with antidepressants.
AB  - Some patients being treated for recurrent major depression experience a return of
      depressive symptoms despite a constant maintenance dose of an antidepressant, a
      phenomenon known as breakthrough depression. A total of 145 psychiatrists who
      were members of the Massachusetts Psychiatric Society responded to a survey about
      intervention in hypothetical cases of breakthrough depression if the patient was
      taking either 20 mg of fluoxetine, 100 mg of sertraline, 100 mg of nortriptyline,
      or 40 mg of fluoxetine. For all drugs and dosages, the most popular choice was
      increasing the dosage, followed by augmenting with lithium or another
      antidepressant or changing to a different drug.

PMID- 9175197
TI  - Collaboration between the Air Force, VA, and a university psychiatry department
      on an inpatient unit.
AB  - The David Grant Medical Center at Travis Air Force Base in California is the site
      of a collaboration between the U.S. Air Force, the Department of Veterans
      Affairs, and the School of Medicine of the University of California, Davis, which
      was begun in 1994 to assure optimum use of resources and provide broader
      educational experiences to residents and students. The three systems have been
      integrated most fully on an inpatient mental health unit. The authors describe
      the history and development of the collaboration, focusing on how the model has
      helped the three organizations address clinical, institutional, and educational
      needs.

PMID- 9175198
TI  - Role of cell adhesion molecules in inflammatory bowel diseases.
AB  - Infiltration of leukocytes into the bowel wall is a landmark of the inflammatory
      bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD). The
      leukocyte movement is dependent on physical contact (adhesion) between the
      leukocytes and activated endothelial cells and can be divided into capturing,
      rolling, leukocyte flattening, and extra-vasation. The molecules shown to form
      the basis of leukocyte-endothelial binding are referred to as cell adhesion
      molecules (CAMs). Several of these molecules have additional properties,
      including interaction between leukocytes and proteins in the extracellular
      matrix, collaen in basement membranes, and stromal cells in lymphoid tissue and
      bone marrow. Furthermore, studies have indicated that CAMs interfere with the
      tumor cell's ability to metastasize. This paper will focus on a description of
      those CAMs that are either known or believed to be involved in the pathogenesis
      of IBD. Investigations of the presence and functions of these CAMs in IBD is
      reviewed, and potential new treatments are discussed.

PMID- 9175199
TI  - Management of esophageal perforations after therapeutic upper gastrointestinal
      endoscopy.
AB  - BACKGROUND: Esophageal perforation is one of the most dreaded complications in
      therapeutic gastrointestinal endoscopy. We assessed the frequency of esophageal
      perforation after endoscopic procedures in a highly specialized endoscopy unit
      and compared clinical outcomes in patients undergoing either surgical or
      conservative management. METHODS: From January 1985 to June 1996, 1011
      instrumental endoscopic procedures (dilatation and bougienage) were performed in
      our department. The computerized complication database was searched to identify
      all patients with esophageal perforation during this same period, and their
      records were reviewed. RESULTS: Seventeen esophageal perforations (1.7%) occurred
      in the course of 1011 procedures. Four perforations resulted from balloon
      dilatation, and 13 were secondary to bougienage. Six patients were managed
      surgically (35%), all of them recovering uneventfully. Eleven patients were
      managed conservatively, mainly because they were unfit for surgery. Survival rate
      in this group was 82%; only two patients died, both of whom had underlying
      malignant disease. CONCLUSIONS: The current concept in management of esophageal
      perforations comprises surgical as well as medical treatment. In well-selected
      cases, non-operative treatment can be considered with favorable results.

PMID- 9175200
TI  - Incidence of antireflux surgery in Finland 1988-1993. Influence of proton-pump
      inhibitors and laparoscopic technique.
AB  - BACKGROUND: The advent of proton-pump inhibitors, and subsequently of the
      laparoscopic technique, can be assumed to have influenced the use of antireflux
      surgery in gastro-oesophageal reflux disease. METHODS: Data on antireflux
      operations carried out in Finland in 1988-93 were obtained from national
      statistics, and the number of operations performed laparoscopically in 1993 was
      ascertained by a questionnaire to all relevant units. The rates per 100,000
      population in the catchment areas were calculated. RESULTS: Antireflux surgery
      almost always implied fundoplication. During 1993, 784 fundoplications and 43
      other antireflux procedures were performed in Finland (total population around 5
      million). The fundoplication rate per 100,000 population rose from 8.8 to 15.4
      between 1988 and 1993. The increase was minimal (8.1-8.2) in 1990-91 when the
      first proton-pump inhibitor, omeprazole, was introduced, but remarkably greater
      (12.8-15.4) in 1992-93, when the laparoscopic technique became popular.
      Differences in fundoplication rates were six to tenfold between health service
      districts and even larger between hospitals. CONCLUSIONS: The numbers of
      antireflux operations in Finland were almost static when proton-pump inhibitors
      were introduced, but rapidly increased after the advent of the laparoscopic
      technique. Remarkable discrepancies were found in the incidence of fundoplication
      between different areas and hospitals.

PMID- 9175201
TI  - Role of metalloproteinases in the development and healing of acetic acid-induced
      gastric ulcer in rats.
AB  - BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are believed to be active in
      connective tissue remodeling associated with various physiological processes and
      in pathological conditions such as cancer and arthritis. However, the role of
      MMPs in gastrointestinal ulceration has not been clearly established. Therefore,
      the aim of this study was to examine the role of collagenase and gelatinases A
      and B in the development and healing of acetic acid-induced gastric ulcer in
      rats. METHODS: Gastric ulcer was induced by injecting 20 microliters glacial
      acetic acid into gastric wall of rat stomachs. To examine whether changes in the
      ulcer formation and healing phase correlate with MMP activity, Triton X-100/CaCl2
      and Tris/CaCl2 (60 degrees C) extracts of stomachs were prepared from controls
      and animals killed 24 h (formation phase) and 7 days (healing phase) after acetic
      acid administration. Total collagenase and gelatinase activities were measured
      using (H3)labeled-acetylated type I collagen or gelatin as substrate,
      respectively, prepared from rat skin. RESULTS: Twenty-four hours after
      administration of acetic acid, the mean area of ulcer crater was 51.2 mm2. By day
      7, the mean size of ulcer crater was reduced to 35.9 mm2. The mean activity of
      collagenase in gastric tissue from controls animals was 0.007 U/g tissue. In
      acetic acid-treated rats, this activity increased to 2.18 U/g at 24 h and
      declined to 0.69 U/g by day 7. Similarly, total gelatinase activity increased
      from 20.5 U/g tissue (controls) to 28.8 U/g at 24 h and declined to 23.9 U/g at
      day 7. Gelatinzymography revealed that gelatinase B levels were greatly increased
      at 24 h and declined by day 7, whereas the gelatinase A levels remained constant.
      CONCLUSIONS: The data showed that the formation of acetic acid-induced ulcer in
      rats is accompanied by an elevation of collagenase and gelatinase B that
      gradually tend to return to control values during the healing phase.

PMID- 9175202
TI  - Bombesin inhibits histamine release from the rat oxyntic mucosa by a somatostatin
      dependent mechanism.
AB  - BACKGROUND AND METHODS: This study examines the effect of bombesin on endogenous
      somatostatin and the histamine-synthesizing enterochromaffin-like cells.
      Somatostatin and histamine were measured in the venous effluent of
      isolated/antrectomized vascularly perfused rat stomachs after administration of
      bombesin and gastrin alone or combined. Histidine decarboxylase (HDC) enzyme
      activity and mRNA abundance were measured in the gastric corpus after intravenous
      administration of bombesin to conscious rats. RESULTS: Bombesin released
      somatostatin from the isolated stomachs and reduced basal and gastrin-stimulated
      venous histamine. Somatostatin antiserum partially reversed the effect of
      bombesin on basal and gastrin-stimulated histamine release. In conscious fed
      rats, intravenous bombesin doubled serum gastrin concentrations and increased HDC
      activity. CONCLUSION: We conclude that endogenous (paracrine) somatostatin
      inhibits basal and gastrin-stimulated histamine release from the ECL cell. In
      intact animals this effect is surmountable by simultaneously released gastrin,
      suggesting that a balance between the effects of gastrin and somatostatin
      determines the activation of the ECL cell.

PMID- 9175203
TI  - Gastroprotective activity of melatonin and its precursor, L-tryptophan, against
      stress-induced and ischaemia-induced lesions is mediated by scavenge of oxygen
      radicals.
AB  - BACKGROUND: Melatonin, a pineal hormone that is biosynthesized from L-tryptophan,
      is known to scavenge oxygen free radicals and to be present in the gut, but
      little is known about the role of this hormone and its precursor, L-tryptophan,
      in protecting the gastric mucosa from damage accompanied by increase in the
      generation of oxygen radicals. METHODS: This study was designed to determine the
      effects of melatonin and L-tryptophan on the formation of acute gastric lesions
      induced by stress and ischaemia reperfusion and, for comparison, by topical
      irritants such as 100% ethanol or acidified acetylsalicylic acid. RESULTS: It was
      found that pretreatment with melatonin in doses ranging from 1.2 to 10 mg/kg dose
      dependently reduced the stress-induced gastric lesions and was accompanied by a
      reduction in blood-free radicals and by attenuation of the fall in gastric blood
      flow. L-tryptophan applied intragastrically in doses ranging from 1 to 100 mg/kg
      also reduced dose-dependently the lesions induced by stress; this effect too was
      accompanied by a rise in gastric blood flow. Pretreatment with indomethacin, to
      block the biosynthesis of prostaglandins, significantly augmented the lesions
      produced by stress and completely abolished the protective effects of melatonin
      or L-tryptophan. Both melatonin and tryptophan reduced the formation of acute
      gastric lesions provoked by ischaemia reperfusion; this was accompanied by an
      increase in gastric blood flow. In contrast, melatonin and L-tryptophan failed to
      influence acute gastric lesions induced by topical irritants such as 100% ethanol
      or acidified aspirin. CONCLUSIONS: Melatonin and L-tryptophan protect the gastric
      mucosa from damage by stress and ischaemia reperfusion, and this action is
      mediated, at least in part, by the limitation in the free radicals, the
      stimulation of mucosal generation of PG and by the increase in gastric blood
      flow.

PMID- 9175204
TI  - Inoculation of VacA- and CagA- Helicobacter pylori delays gastric ulcer healing
      in the rat.
AB  - BACKGROUND: Helicobacter pylori is associated with peptic ulcer disease. In the
      present study, the influence of VacA and CagA- H. pylori on gastric ulcer healing
      was studied in the rat. METHODS: Twenty-four rats with acetic-acid-induced
      gastric ulcer were divided into two groups and given either vehicle (Brucella
      broth) or H. pylori suspension by gavage every 12 h for 7 days. The animals were
      killed 1 and 8 days after the last H. pylori gavage (i.e. 10 and 17 days after
      the induction of the ulcer). One hour before death, 3H-thymidine was given
      intraperitoneally. Tissue samples from the stomach (including the ulcer area) and
      the duodenum were processed for determination of labelling index and apoptotic
      cells. RESULTS: Compared with the vehicle-treated controls, the ulcer area in H.
      pylori-inoculated rats was significantly larger, the epithelial apoptotic cells
      in the ulcer margin and intact corpus were more numerous, while the cell
      proliferation of gastroduodenal epithelium was slightly, but not significantly,
      increased by H. pylori gavage. CONCLUSION: Gastric ulcer healing was delayed
      after the inoculation of VacA- and CagA- H. pylori in the rat, possibly as a
      result of excess cell loss by apoptosis.

PMID- 9175205
TI  - Colony variation of Helicobacter pylori: pathogenic potential is correlated to
      cell wall lipid composition.
AB  - BACKGROUND: Differences in expression of disease after infection with
      Helicobacter pylori have so far been connected with host factors and bacterial
      interstrain variation. In this study, spontaneous and ecology-mediated
      intrastrain variation was examined. METHODS: Four clinical isolates of H. pylori
      were shown to give rise to two colony forms. Bacterial morphology was examined by
      electron microscopy. Bacterial fractions were examined for proteins using ion
      exchange chromatography and SDS-PAGE; for lipids using thin-layer chromatography,
      lipid anion-exchange chromatography, column chromatography on silica gel, 31P
      NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness
      and adhesiveness were examined in two different systems, and urease and VacA
      toxin were assayed by Western blot analysis. RESULTS: H. pylori was shown to give
      rise to two colony forms: at normal pH the population was dominated by L
      colonies. One strain was chosen for further studies. Bacteria from L colonies
      retained VacA toxin and urease, did not invade or adhere to epithelial cells, and
      contained normal quantities of phosphatidylethanolamine. In a small frequency,
      spontaneous S colonies were formed. Bacteria from these colonies released VacA
      and urease, adhered to and invaded epithelial cells and contained increased
      amounts of lysophosphatidyl ethanolamine and phosphatidyl serine. After addition
      of HCl to the culture medium (pH6), almost only S colonies were formed. The
      results demonstrate that environmental factors, such as HCl, can change the
      bacterial cell wall, and thereby enhance expression of virulence factors of H.
      pylori in vitro. A similar in vivo variation would have implications for our
      understanding of the interaction between HCl secretion in the gastric mucosa and
      H. pylori in the development of peptic ulcer disease.

PMID- 9175206
TI  - Flagellin gene diversity among Helicobacter pylori strains and IL-8 secretion
      from gastric epithelial cells.
AB  - BACKGROUND: To clarify the pathological functions of the virulence factors of
      Helicobacter pylori, a comparative analysis was carried out on the relationship
      between motility, flagellar gene polymorphism, vacuolating cytotoxin (VT)
      production and interleukin-8 (IL-8) induction. METHODS: Twenty-five strains were
      examined for restriction fragment length polymorphism (RFLP) of the flagellin
      gene. Motility was measured using semisolid agar plates. Cytotoxicity was assayed
      using RK-13 cells. IL-8 secretion was assessed by the enzyme-linked immunosorbent
      assay (ELISA) methods. RESULTS: H. pylori was classified into four groups
      according to their flagellar RFLP. No differences were noted in motility or VT
      production among the four groups, but a significant difference was noted in IL-8
      induction. In addition, highly motile strains produced more IL-8. CONCLUSION:
      This flagellar genetic polymorphism may be associated with IL-8 induction.

PMID- 9175207
TI  - Helicobacter pylori infection accelerates gene expression of glicentin in the
      gastric mucosa. Its association with intestinal metaplasia of the stomach.
AB  - BACKGROUND: Glicentin is an intestinal polypeptide hormone which seems to promote
      intestinal metaplasia (IM) in the gastric mucosa. The aim of this study was to
      clarify whether Helicobacter pylori infection accelerates glicentin gene
      expression. METHOD: Glicentin mRNA was investigated by reverse-transcription
      polymerase chain reaction using gastric biopsies from 47 patients examined
      endoscopically and denying IM. RESULTS: IM was observed in 18 (38.3%) cases
      histologically, but not in the other 29 (62.7%). Glicentin mRNA was significantly
      correlated with histological IM (P < 0.01) and was positively correlated with H.
      pylori infection (P < 0.05). CONCLUSION: Our results indicate that H. pylori
      infection is associated with the induction of glicentin in the gastric mucosa,
      thus supporting the hypothesis that H. pylori infection accelerates IM of the
      stomach.

PMID- 9175208
TI  - High prevalence of the CagA-positive Helicobacter pylori strains in Japanese
      asymptomatic patients and gastric cancer patients.
AB  - BACKGROUND: Several studies have shown that infection of Helicobacter pylori
      strains possessing cagA is associated with atrophic gastritis and gastric
      cancers. METHOD: In 58 pairs of early gastric cancer patients and sex- and age
      matched controls, isolated H. pylori strains were tested for possession of cagA.
      The presence of atrophic gastritis was also examined. RESULTS: Proportions of
      cagA-positive strains were 100% in cancer patients and 92.3% in controls.
      Atrophic gastritis was seen in 96.7% and 95.8% of cancer and control patients in
      whom cagA-positive strains (NS) were detected. However, it was seen in only 20%
      of H. pylori-negative control patients (P < 0.01). CONCLUSIONS: The present
      results do not suggest any specific association between cagA-positive strains and
      gastric cancer. However, frequent prevalence of cagA-positive strains might be
      associated with the high incidence of atrophic gastritis in Japanese populations.

PMID- 9175209
TI  - Gastric as well as duodenal biopsies may be useful in the investigation of iron
      deficiency anaemia.
AB  - BACKGROUND: Iron absorption is known to be impaired in the setting of gastric
      achlorhydria, yet gastric atrophy is not usually considered an aetiological
      factor for iron deficiency anaemia. We aimed to determine the prevalence of
      achlorhydric gastric atrophy in patients with iron deficiency and no identifiable
      source of gastrointestinal blood loss, and to assess whether gastric, as well as
      duodenal, biopsies should be routinely performed in these patients. PATIENTS:
      Forty-one consecutive patients with iron deficiency anaemia and no specific
      gastrointestinal symptoms or evidence of a bleeding lesion on faecal occult blood
      testing or upper gastrointestinal or colonic endoscopy. METHODS: As well as
      routine duodenal biopsies, samples were taken from gastric corpus and antrum for
      evidence of gastric atrophy. Achlorhydria was considered to be present if plasma
      gastrin measured on a sample obtained with the patient fasting was over 200 ng/l.
      Serum was tested for intrinsic factor and gastric parietal cell antibodies.
      RESULTS: Haemoglobin concentrations ranged from 4.1 to 10.9 g/dl. Eight (20%) of
      the 41 patients had corpus-predominant or generalized atrophy and high plasma
      gastrin levels, of whom six had serum intrinsic factor and/or gastric parietal
      cell antibodies: two also had Giardia lamblia organisms in duodenal biopsies.
      Four other patients (10%) had villous atrophy of the duodenum. CONCLUSIONS: As
      well as confirming the importance of seeking coeliac disease in patients with
      iron deficiency anaemia, our results suggest that achlorhydric gastric atrophy is
      also a common association. Gastric biopsies should be taken in patients with no
      other explanation for anaemia. The finding of Giardia organisms in two
      achlorhydric patients, with a possible contributory role, suggests that duodenal
      biopsies should be obtained even if serum coeliac-related antibodies are absent.

PMID- 9175210
TI  - The release of gastric inhibitory peptide, glucagon-like peptide-I, and insulin
      after oral glucose test in colectomized subjects.
AB  - BACKGROUND: The physiologic role of the colon as an endocrine organ is not clear.
      We therefore studied the enteroinsular axis in patients with ulcerative colitis
      after colectomy. METHODS: The subjects included 11 patients with a conventional
      ileostomy, 10 patients with an ileoanal reservoir, and 10 normal controls. The
      concentrations of glucose, insulin, gastric inhibitory peptide (GIP), and
      glucagon-like peptide-I (GLP-I) were measured in plasma during an oral glucose
      test. RESULTS: The peak level of glucose and peak levels and area under the curve
      (AUC) of insulin and GIP were higher in patients (P < 0.05). Neither the peak
      level nor the AUC of GLP-I differed between patients and controls, but time to
      peak level was four times longer in patients with an ileoanal reservoir (P <
      0.05). CONCLUSION: Colectomy seems to affect the enteroinsular axis, leading to
      hyperinsulinemia and an impaired glucose tolerance. Moreover, patients with an
      ileoanal reservoir have a slower GLP-I response after intake of glucose.

PMID- 9175211
TI  - Regional differences in the effect of mucosal glucose and amino acids on ion
      transport in normal and cholera toxin-stimulated porcine small intestine.
AB  - BACKGROUND: This study explores regional differences in the response to mucosal D
      glucose and L-amino acids in both normal intestine and intestine stimulated with
      cholera toxin. METHODS: Proximal, mid and distal small intestines from 6- to 8
      week-old pigs were bathed in Ussing chambers with a buffer containing 15 mM
      serosal glucose, and the effect of adding a cocktail giving luminal chamber
      concentrations of 15 mM D-glucose and 20 mM of each L-alanine, L-proline, L
      lysine, L-phenylalanine, and L-glutamine on transmucosal Na+ and Cl- transport
      was measured. RESULTS: In all segments of both normal and cholera toxin-treated
      intestine, electrogenic Na+ and electroneutral NaCl absorption were promoted. No
      significant differences in the net increase of Na+ and Cl- absorption between
      normal and cholera toxin-stimulated intestine were present. Under both conditions
      no segmental differences were present in the stimulated Cl- absorption,
      describing identical capacity for stimulated electroneutral NaCl absorption. In
      contrast the electrogenic Na+ absorption was, compared to the proximal part,
      doubled in the mid and distal parts under both conditions. CONCLUSIONS: We
      conclude that mucosal D-glucose and L-amino acids stimulate electroneutral NaCl
      and electrogenic Na+ absorption to the same degree in normal and cholera toxin
      treated small intestine. There is no segmental difference in stimulated
      electroneutral NaCl absorption, while electrogenic Na+ absorption is highest in
      mid and distal parts.

PMID- 9175212
TI  - Expression of the epidermal growth factor receptor gene in human intestinal
      metaplasia: a preliminary report.
AB  - BACKGROUND: The role of growth factors/receptors in the etiopathology and/or
      development of gastric cancer has recently come under scrutiny, since
      overexpression or amplification of the EGF system has been found in many
      intestinal type gastric cancers and related to a more aggressive behavior. Since
      these gastric carcinomas appear to develop from intestinal metaplasia, a study
      was planned to investigate whether overexpression of the EGF-receptor gene also
      occurred in intestinal metaplastic mucosa. METHODS: Patients underwent upper GL
      endoscopy. Gastric biopsies for routine histology, Helicobacter pylori detection,
      quantification of intestinal metaplasia and EGF-R expression analysis were
      performed. A 30mer EGF-R specific oligonucleotide was end-labeled and used to
      probe a dot blot filter containing the RNA from the bioptic samples. RESULTS:
      Though all the gastric samples transcribed the EGF-R gene to a detectable level,
      overexpression of the EGF-R gene was found in the metaplastic mucosa in a
      minority of patients. CONCLUSIONS: These preliminary findings suggest that
      overexpression of the EGF-R gene is infrequent in the metaplastic gastric mucosa.

PMID- 9175213
TI  - Quality of life measurement after rectal excision for cancer. Comparison between
      straight and colonic J-pouch anastomosis.
AB  - BACKGROUND: The patients in this study formed part of a multicentre randomized
      trial comparing the straight and colonic pouch anastomoses after rectal excision
      for cancer. The trial reflected an advantage of the pouch group regarding
      frequency, urgency and incontinence. We hypothesized that such differences in
      bowel function would be reflected in a general quality of life score. METHODS:
      Forty-five patients were randomized. The Nottingham Health Profile was used to
      measure health-related quality of life before and 1 year after surgery. RESULTS:
      There was no difference in quality of life score when the two groups were
      compared. When calculating the relative change after surgery, there was an
      improvement in both groups regarding the total score of the Profile (P < 0.0001).
      CONCLUSIONS: The Nottingham Health Profile was effective in showing an
      improvement in quality of life in both groups after surgery. The observed
      difference in clinical bowel function was not, however, reflected in an improved
      quality of life score as measured by the Profile.

PMID- 9175214
TI  - Non-invasive assessment of inflammatory activity and fibrosis (grade and stage)
      in chronic hepatitis C infection.
AB  - BACKGROUND: Much effort has been expended in finding non-invasive alternatives to
      percutaneous liver biopsy for assessing the histological extent of liver damage.
      METHODS: We have evaluated the relationship between various histological features
      of liver of biopsies and plasma levels of immunoglobulin G (IgG), procollagen III
      propeptide (PIIIP) and type-IV collagen (CL-IV) in 109 patients with chronic
      hepatitis C (HCV) infection. RESULTS: The serum IgG level was the best single
      marker for distinguishing chronic persistent hepatitis (CPH) from chronic active
      hepatitis (CAH). The mean serum levels of PIIIP and CL-IV increased with the
      progression of liver disease, though the three variables manifested considerable
      overlap in individual values as markers of CPH, CAH and cirrhosis. The various
      biochemical markers correlated weakly but significantly to both histological
      grade and stage of liver disease, as assessed with the scoring system of Knodell.
      The correlation appeared to be non-specific and to reflect inflammatory activity
      as well as fibrogenesis. CONCLUSIONS: Serum levels of PIIIP. CL-IV and IgG are of
      limited use in predicting the histological grade and stage of liver disease in
      patients with chronic HCV infection.

PMID- 9175215
TI  - Transendoscopic ultrasonography during conventional upper gastrointestinal
      endoscopy. Clinical evaluation of a linear 20-MHz probe system.
AB  - BACKGROUND: Endoluminal ultrasonography provides detailed images of the
      gastrointestinal wall and surrounding tissue. Miniature ultrasound probes can be
      applied during conventional endoscopy. METHODS: The supplementary diagnostic
      information obtained during endoscopy with a linear 20-MHz ultrasound probe
      system was independently assessed by two observers applying a general rating
      system on 188 consecutive examinations in 173 patients. RESULTS: On average, 70%
      of the examinations were found to contribute conclusive or important
      supplementary information that could potentially influence treatment or further
      patient evaluation (substantial diagnostic yield). Substantial diagnostic yield
      was most often obtained in patients with known malignancy (92%), stenoses (81%),
      or subepithelial masses (80%) and more often in patients with malignant (85%)
      than in those with benign (61%) conditions (P < 0.001). CONCLUSIONS:
      Transendoscopic ultrasonography using a 20-MHz linear miniature ultrasound probe
      may provide substantial supplementary diagnostic information during upper
      gastrointestinal endoscopy, especially in patients with malignant disease and
      with stenotic or subepithelial lesions.

PMID- 9175216
TI  - Addison's disease and selective IgA deficiency in two coeliac patients.
AB  - Coeliac disease is associated with selective IgA deficiency and various
      autoimmune disorders. An association between Addison's disease and coeliac
      disease has been documented previously in the literature but never heretofore in
      coeliac patients with selective IgA deficiency. From a coeliac registry of over
      700 biopsy-proven coeliac patients, studied closely over a 25-year period at
      University College Hospital, Galway, we now report the finding of Addison's
      disease and selective IgA deficiency in two patients with established coeliac
      disease. Previous reports of Addison's disease in coeliac patients were sporadic,
      and it was felt that the association between the two conditions was fortuitous.
      We now believe that coeliac patients, especially those who are selectively
      deficient in serum IgA, should be followed up with increased vigilance, as the
      association between IgA-deficient coeliac patients and Addison's disease is
      greater than can be explained by chance. Furthermore, we suggest that patients
      with established Addison's disease may have subclinical coeliac disease and
      should be screened with anti-reticulin or anti-endomyseal antibodies.

PMID- 9175217
TI  - Classification of acute pancreatitis and the role of prognostic factors in
      assessing severity of disease.
AB  - Clinical assessment of acute pancreatitis by experts is as accurate as any of the
      individual approaches which have been recommended. What is important in a
      hospital setting is for one or more of these systems to be applied in individual
      hospitals so that forewarning is given, especially to the less experienced
      clinicians, of the patient who is likely to run into difficulties and requires
      high dependency or intensive care. One practical approach which can be personally
      recommended is to employ the Glasgow scoring system plus C-reactive protein
      levels and also to take into account body mass index. Any patient with three
      positive Glasgow factors, or CRP > 150 mg/l or BMI > 30 kg/m2 has severe acute
      pancreatitis. More refined systems may ultimately be developed but we are still
      some way from a single substance in blood or urine being easily and cheaply
      measured and representing an accurate prognostic indicator of severe acute
      pancreatitis. Part of the journey has been completed but there is still
      considerable potential to make the rest of the journey an improvement for both
      clinicians and patients.

PMID- 9175218
TI  - Myocardial protection by pressure- and volume-controlled continuous hypothermic
      coronary perfusion (PVC-CONTHY-CAP) in combination with ultra-short beta-blockade
      and nitroglycerine.
AB  - The aim of the study was to validate clinically a new technique of myocardial
      protection developed for intra- and extra-cardiac surgery on the beating heart.
      The concept combines the principle of continuous pressure- and volume-controlled
      coronary artery perfusion (PVC-CONTHY-CAP) with the specific myocardioprotective
      effects of hypothermia and nitrates and, on the other hand, with the beta-blocker
      mediated reduction of chronotropy and inotropy necessary for convenient surgery.
      Under standard ECC conditions after cross-clamping the aorta coronary perfusion
      with oxygenated blood enriched with nitroglycerine (10 micrograms/kg/h) and
      esmolol (0.05 mg/ml flow/min) is started via an additional perfusion cannula
      placed in the aortic root. The temperature of the perfusate is maintained at 32
      degrees C, the intraaortic pressure at 40-70 mmHg and the perfusion flow in the
      range 0.8-1.0 ml/g heart muscle/min. In CABG procedures an additional perfusion
      catheter is used for perfusion of distal coronary artery segments. Using this
      technique 100 consecutive patients, adults and children, were operated on between
      2/96 and 8/96. In 84 adult patients (age: 45-82 yrs), 78 CABG procedures (54
      elective, 13 urgent, 11 acute) with a mean bypass count of 3.7 (range 1-7), 69
      ITA grafts, 72 grafts to CX, and 3 MVRec/MVRpl, and 6 pure MVRec/MVRpl procedures
      (1 urgent, 1 emergency) were performed. The mean coronary perfusion time was 48
      min (range 21-88 min). In 5 patients perioperative infarction (CABG; 1 emergency
      after PTCA, 4 elective) with significant increase of CK-MB values (57-98 U/L)
      occurred. In the 4 elective patients (3 with diabetes mellitus) re-intervention
      was not possible due to small-vessel disease. In one patient with preoperative
      infarction IABP was necessary. No patient died. There were 16 children (age:
      4weeks-16 yrs): VSD, n = 6, AV-C, n = 2, TOF, n = 1, MVRec, n = 1, DORV
      (Rastelli), n = 2, SV (TCPC), n = 3, and PV obstruction, n = 1. The mean coronary
      perfusion time was 97 min (range: 27-260 min). The mean ICU stay 3.9 d (range: 1
      10 d). One child died (TCPC) on the 10th postoperative day due to multi-organ
      failure. In conclusion, PVC-CONTHY-CAP is designed especially for emergency and
      urgent procedures, i.e. patients with PTCA-related complications, patients with
      severely depressed LV function, and patients with complex congenital cyanotic
      heart defects. Using PVC-CONTHY-CAP, coronary artery bypass grafting as well as
      intracardiac procedures for congenital and acquired heart defects can be
      performed safely and conveniently, the system is easy to handle for both the
      cardiac surgeon and perfusionist. Due to its pharmacological properties
      continuous intracoronary application of nitrates in combination with hypothermia
      seems to be essential as a preventive treatment modality for the ischemic state.

PMID- 9175219
TI  - Vascular complications related to intraaortic balloon counterpulsation: an
      analysis of ten years experience.
AB  - We have performed a retrospective review of our experience with the intraaortic
      balloon counterpulsation pump (IABP) during the last decade, to identify aspects
      of risk factors, complications, and management that affect peripheral vascular
      morbidity and mortality. Data from 472 patients who had the IABP inserted during
      the ten-year period from December 1985 to December 1995 were retrospectively
      reviewed. Risk factors, implantation techniques, complications, and significant
      variables were evaluated. One hundred forty-five vascular complications needed
      surgical therapy in 116 patients. Mean age was 62.2 +/- 12.9 years. There were 84
      (72.5%) men and 32 (27.5%) women. Mortality rate was 28.3% (n = 181). The
      mortality for patients with ischemic vascular complications was significantly
      higher than in patients who did not suffer any vascular complication (59.6% vs
      30.1%, p = 0.0001). Complications included acute limb arterial occlusion in 99
      cases (68.3%), compartment syndrome in 27 (18.6%), groin hematoma in 15 (10.3%),
      and persistent lymph fistula in 4 (2.8%). Of these, 97 (76.9%) occurred during
      IABP therapy and 29 (23.1%) after IABP explantation. Thromboembolectomy was
      required for 61 (42.2%) of the ischemic limbs. Associated procedures were 24
      (16.5%) profundaplasties, 10 (7%) infrainguinal bypasses (5 (3.4%)
      femoropopliteal supragenicular, 3 (2.2%) femoropopliteal infragenicular, and 2
      (1.4%) infrapopliteal), 26 (17.9%) fasciotomies, and 5 (3.4%) amputations. A
      history of peripheral vascular disease (31 patients [43.6%] with vs 95 [23.6%]
      without, p < 0.05) and the presence of diabetes mellitus (70 patients [49.2%]
      with vs 56 [16.9%] without) increased the risk of limb ischemia significantly.
      Female sex, insertion of IABP by percutaneous technique, and direct removal with
      groin compression were associated with higher ischemic complication rates, the
      differences however were not significant. Itis concluded that 1. Limb ischemia
      remains the primary complication after IABP insertion; 2. Femoral artery
      thromboembolectomy is usually sufficient for revascularisation; 3. Adequate
      implantation and surgical explantation techniques are essential to reduce the
      IABP-related morbidity; 4. Identification of subclinical disease may aid in the
      management of subsequent acute limb ischemia; 5. The presence of peripheral
      vascular disease and diabetes mellitus are associated with higher ischemic
      complication rates.

PMID- 9175220
TI  - The effect of preoperative intra-aortic balloon pump support in patients with
      coronary artery disease, poor left-ventricular function (LVEF < 40%), and
      hypertensive LV hypertrophy.
AB  - Poor left-ventricular function, hypertension, and left-ventricular hypertrophy in
      patients with coronary artery disease (CAD) undergoing coronary artery bypass
      grafting (CABG) are associated with increased operative risks. Between June 1994
      and March 1996, 33 patients undergoing CABG, were randomized into 2 groups. One
      group (IABP group, n = 19) received IABP treatment on average for 2 hours prior
      to CPB, the other group (control group, n = 14) had no preoperative IABP, Cardiac
      performance was measured pre- and postoperatively by Swan-Ganz catheter. Mean age
      was 65 years and 90% were men. All patients had a preoperative LVEF < or = 40%
      (mean 32.6 +/- 11.1%), 3-vessel disease, established hypertension (WHO criteria),
      and LV hypertrophy (ventricular mass > or = 136 g/m2 [men] or > or = 110 g/m2
      [women]). Ischemia time was similar in both groups while CPB-time was shorter in
      the IABP group, p < 0.05. There were no hospital deaths in the IABP group, but 3
      in the control group suffered postoperative low cardiac output. Nine patients
      (64%) in the control group required IABP support postoperatively, but only 20% of
      the patients in the IABP group had a shorter ICU stay, 2.4 +/- 0.9 vs. 3.4 +/-
      1.1 days, p < 0.01. Cardiac index increased significantly in the IABP group prior
      to CPB and was higher compared to control, p < 0.001. Five min after CBP cardiac
      index was higher in the IABP group than in the control group, p = 0.013, and
      continued to increase thereafter, while no further improvement was observed in
      controls. Preoperative IABP treatment in hypertensive patients with CAD, low LVEF
      and LV hypertrophy who are undergoing CABG is beneficial. An improved cardiac
      performance pre- and postoperatively was associated with a lower rate of hospital
      mortality and less postoperative morbidity, as well as shorter ICU stay. The
      treatment is cost-beneficial.

PMID- 9175221
TI  - Long-term results of surgical subxiphoid pericardial drainage.
AB  - A series of 64 consecutive patients who underwent surgical subxiphoid drainage of
      pericardial effusion over an 11-year period, was analysed both for recurrence of
      pericardial pathology and survival. The mean follow-up time was 4 years (6 months
      to 10 years). Twelve patients had recurrent effusion (18%), all except one within
      6 months: six patients (9%) had another drainage procedure which was the
      definitive treatment except in one terminal cancer patient with intractable
      malignant effusion who died of cardiac tamponade. The remaining six recurrent
      effusions could be treated conservatively. One patient with idiopathic effusion
      developed late constrictive pericarditis. Patients with underlying malignancy (n
      = 26) had significantly worse actuarial survival than the others (actuarial
      survival at 1 and 5 years of 51% and 0% vs 87% and 76%, respectively). However,
      their probability of remaining free of recurrence did not differ significantly
      (actuarial freedom at 1 year of 89% vs 76%). In conclusion, subxiphoid drainage
      provides a simple, safe and expeditious treatment of most symptomatic pericardial
      effusions with one in ten patients requiring a repeat drainage for recurrence. In
      particular, it offers a good palliation in most patients with underlying
      neoplastic disease. Routine echocardiography is recommended at one and six months
      to catch most of the recurrent effusions.

PMID- 9175222
TI  - Morphologic characterization and assessment of mitral regurgitation after repair
      of atrioventricular defects in children.
AB  - Severe postoperative mitral regurgitation renders information on the underlying
      mechanism before reoperation very important, as a potential for mitral valve
      reconstruction may facilitate the decision whether to reoperate, especially in
      the very young. This study compares the efficacy of transthoracic echo
      cardiography (TTE) and left-ventricular angiography with that of transesophageal
      echocardiography (TEE) for detection of the mechanism underlying mitral
      regurgitation and its quantitative assessment in children after repair of common
      atrioventricular septal defect. Five children aged 1.5 to 16 years were evaluated
      by TTE, TEE, and angiography for postoperative mitral regurgitation 1 to 21
      months after initial repair. TEE showed septal detachment of the mitral leaflet
      in four patients and reopening of the mitral cleft in one patient as the cause of
      mitral regurgitation whereas TTE failed in four and angiography in all patients.
      TEE allows definite identification of morphologic characteristics of mitral
      regurgitation and reliable assessment of its severity. Thus redo surgery may be
      safety performed on the bases of TEE findings alone without confirmation by
      cardiac catheterization.

PMID- 9175223
TI  - Results of cardiac operations in five kidney transplant patients.
AB  - Because of the paucity of literature reports about cardiac operations in renal
      transplant patients we performed a retrospective study encompassing all such
      patients operated upon in our institution in 1993 and 1994. During this time 5
      renal transplant patients underwent cardiac surgical procedures between 1 and 9
      years after transplantation: in 4 patients coronary artery bypass grafting (CABG)
      was carried out and in one patient aortic valve replacement. We analyzed pre-,
      peri-, and postoperative data. Late results were obtained by questionnaire from
      the patients' primary physicians. Short- and long-term results were excellent.
      Mortality was 0%. At late follow-up (8-23 months) all patients were in NYHA class
      II or better. Postoperatively all patients experienced a clear improvement of
      their cardiac symptoms. None of the transplanted kidneys deteriorated. One
      patient who had to undergo intermittent hemodialysis preoperatively improved so
      much that she did not require any dialysis postoperatively. Although the total
      number of patients in this study is limited we believe it can be stated that
      renal transplant patients can undergo cardiac operations with generally good
      results.

PMID- 9175225
TI  - Experimental gluing of lung parenchyma in rats.
AB  - Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin
      resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less
      histotoxic dialdehydes, ethandial and pentandial. The aim of the present study
      was to evaluate the usefulness of this modified composition in gluing defects in
      lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in
      length and 0.8 cm in depth were closed by application of gelatin-resorcinol
      dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were
      sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of
      postoperative days 28 and 120. Macroscopic examination revealed a tight closure
      of the parenchymal defects in all postoperative stages. Initially by an adhesive
      layer and later on by granulation tissue and scar tissue respectively. On
      microscopic examination an inflammatory tissue response with polymorphonuclear
      neutrophils and macrophages predominating was found 2 days postoperatively. After
      7 days multinucleated giant cells appeared. On postoperative day 14 the tissue
      response presented a distinct granulomatous character with multinucleated giant
      cells persisting. After 28 days remnants of adhesive surrounded by granulation
      tissue were detectable. On postoperative day 120 the adhesive had been completely
      resorbed and the parenchymal defect was replaced by fibrous scar tissue. The
      gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma
      in rats. The adhesive is resorbed completely and does not interfere with
      parenchymal healing.

PMID- 9175224
TI  - Inhibition of inducible nitric oxide synthase prolongs rat lung allograft
      survival.
AB  - Nitric oxide (NO) has been demonstrated to be an important immunoregulation
      molecule in the process of cellular immunologic interactions. Our recent results
      demonstrated that NO is produced in association with acute allograft rejection
      and NO inhibition may suppress rejection histologically. This data provides
      direct evidence of NO in allograft rejection and the immunosuppressive potential
      of NO inhibitors. In this paper, the effect of NO inhibition on allograft
      survival was evaluated to investigate the capacity of NO inhibitors as
      immunosuppressive agents. Seventeen rat left lung transplants from BN donors to
      F344 recipients were accepted for this study. After surgery, recipients were
      randomized into two groups and received either aminoguanidine (AG), a highly
      selective NO synthase inhibitor, 200 mg/kg, intra-peritoneal every 6h (n = 13) or
      normal saline treatment (n = 4). No production was determined from the
      recipient's serum nitrite and nitrate levels. Graft survival was monitored via
      semi-quantitative radiographic aeration scores (AS: 0 = opaque lung to 6 = normal
      appearing lung). The nitrite and nitrate levels were clearly detectable before
      the radiographic finding associated with rejection became obvious. Production of
      NO was significantly inhibited by AG treatment. AG treatment prolonged allograft
      survival radiographically (12.0 days and 6.0 days for treated and untreated
      groups respectively, p = 0.0001). These data suggest that the inducible NO is
      produced in association with acute lung allograft rejection and may serve as a
      sensitive rejection marker. NO inhibition significantly prolonged rat lung
      allograft survival but failed to induce immunological tolerance.

PMID- 9175226
TI  - Reoperation of coronary artery bypass with right gastroepiploic artery on a
      beating heart.
AB  - The case of a 67-year-old male with double-vessel coronary artery disease
      combined with a severely calcified ascending aorta, moderate aortic
      insufficiency, cholecystic stones, and unruptured intracranial aneurysm is
      presented. Successful coronary artery bypass reoperation is described using the
      right gastroepiploic artery through an additional left anterior thoracotomy on
      the beating heart.

PMID- 9175227
TI  - Trapped thrombus in a patent foramen ovale.
AB  - We report two cases of impending paradoxical embolism through a patent foramen
      ovale. A 73-year-old male had recurrent pulmonary embolism and a large thrombus
      trapped in a patent foramen ovale. The other patient, a 70-year-old male had
      septic mediastinitis after prior bypass surgery and a large thrombus lodged in a
      patent foramen ovale. Cardiac embolectomy and closure of the foramen ovale was
      performed in both cases because of impending paradoxical embolism. In addition
      pulmonary thromboendarterectomy was performed to relieve pulmonary hypertension.
      Therapeutical options are discussed.

PMID- 9175228
TI  - Repair of coarctation of the aorta in adults with simultaneous aortic valve
      replacement and coronary artery bypass grafting.
AB  - The authors present three patients who had either coronary artery disease or
      severe aortic stenosis or both along with congenital coarction of the aorta. The
      use of a heterotopic bypass (Dacron tube implanted between the ascending and
      descending aorta) allowed the surgeons to correct the coarction through a median
      sternotomy and perform the coronary artery bypass grafting and valve replacement
      at the same time. The authors are convinced that the scarcely mentioned
      heterotopic bypassing of the coarcted aorta should be added to the armamentarium
      of the surgeons who operate on patients with coarctation or recoarctation of the
      aorta in adulthood or with coarctation that is associated with cardiac lesions.

PMID- 9175229
TI  - Aortitis, aortic valve incompetence, and left coronary ostium stenosis in a
      patient with C-ANCA-associated necrotizing vasculitis.
AB  - Aortitis with involvement of the aortic valve is rarely associated with
      vasculitis syndromes. We present a patient with antibodies to a neutrophil
      cytoplasmic antigen-associated (ANCA) vasculitis with renal failure who developed
      aortic incompetence as a result of aortitis which involved the aortic valve.
      Thickening of the aortic wall also caused stenosis of the left coronary ostium.

PMID- 9175230
TI  - An updated report of a case of lung cancer resected using cardiopulmonary bypass.
AB  - Although surgical intervention for advanced lung cancer invading the aortic wall
      is challenging, we successfully carried out such radical surgery under
      cardiopulmonary bypass as previously reported in this journal. One patient has
      now been followed for more than 5 years after the operation, so that we conclude
      if there is no evidence of metastatic cancer in selected patients then complete
      resection should be attempted using circulatory support, with the hope of an
      occasional cure.

PMID- 9175231
TI  - Accuracy of two newly described D-dimer tests in patients with suspected deep
      venous thrombosis.
AB  - Accumulating evidence suggests that the ELISA determination of D-Dimer might be a
      useful tool for the exclusion of deep vein thrombosis (DVT) of lower extremities,
      because of its high sensitivity and negative predictive value. However,
      conventional ELISA assay is time-consuming and, therefore, is not suitable for
      emergency use. To evaluate the accuracy of two rapid assays recently described,
      126 consecutive outpatients with the clinical suspicion of DVT underwent the
      NycoCard D-Dimer and the Instant I.A. D-Dimer determination, using venography as
      the reference test. In all patients, the conventional ELISA assay was also
      performed. Venography confirmed the presence of DVT in 30 patients (23.8%), and
      ruled out the diagnosis in the remaining 96. Instant I.A D-Dimer was positive in
      28 patients with DVT (sensitivity, 93.3%), and negative in 90 subjects free from
      thrombosis (specificity, 93.8%). Nycocard D-Dimer correctly identified 27
      patients with DVT (sensitivity 90.0%), and was negative in 77 subjects free from
      thrombosis (specificity, 80.2%). Sensitivity, specificity, negative and positive
      predictive values of both tests did not differ from those found with the classic
      ELISA method. In conclusion, both Instant I.A. D-Dimer and Nycocard D-Dimer
      assays show a great potential for clinical use.

PMID- 9175232
TI  - Central venous thrombosis: an early and frequent complication in cancer patients
      bearing long-term silastic catheter. A prospective study.
AB  - Studies on catheter-related central venous thrombosis (CRCVT) have been focused
      mainly on clinically evident CRCVT due to occlusive thrombi, underestimating
      therefore the actual thrombosis prevalence. This prospective study was aimed at
      evaluating prevalence, timing and evolution of thrombosis, and identifying
      involved veins and risk factors in cancer patients (pts) undergoing percutaneous
      subclavian central venous catheterization (CVC) for chemotherapy, parenteral
      nutrition or both. We enrolled 127 consecutive pts requiring partially or totally
      implanted central venous silastic catheters. The study protocol included
      peripheral phlebography (P) at day 8, 30 and every two months following CVC
      and/or when clinically indicated, along with peripheral and pullout P on catheter
      withdrawal. A quantitative scale was developed to evaluate thrombus grading in
      subclavian, innominate and cava veins. Age, sex, coagulation profile tumor
      histotype, metastases, therapy, catheter type, and catheter insertion side were
      also investigated. Only pts who underwent at least two P were evaluated, and chi
      2 test was adopted for statistical analysis. Altogether, 95 pts were evaluable.
      CRCVT was observed in 63/95 (66%) pts. At day 8, 30 and 105 (representing the
      median days in which first, second and last P were performed) CRCVT was evidenced
      in 64%, 65% and 66% of the pts, respectively. Thrombus grading did not differ
      among first, second and last P. CRCVT was symptomatic in 4/63 (6%) pts.
      Thrombosis prevalence was higher in subclavian (97%) with respect to innominate
      (60%) or cava (13%) veins (p < 0.001). Thrombosis was higher in left subclavian
      catheters (14/16; 87.5%) than in right ones (49/79; 62%), p < 0.01. No
      associations were established between CRCVT and other investigated parameters.
      Our data show a very high actual frequency of CRCVT in cancer pts, and emphasize
      that first days following CVC are at the highest risk for CRCVT development.
      Based on our results, a study on short-term antithrombotic prophylaxis in cancer
      pts requiring CVC is warranted. Finally, our data indicate that left subclavian
      vein catheterization represents a risk factor for CRCVT.

PMID- 9175233
TI  - Adjuvant effect of argatroban on staphylokinase induced thrombolysis of platelet
      rich thrombi in rat mesenteric venules in vivo.
AB  - Effective, therapeutic thrombolysis should not only promote dissolution of fibrin
      but should also regulate continued thrombin-induced fibrin formation and the
      accumulation of platelets on the thrombotic lesion. The aim of the present study
      was to assess the use of a synthetic, low molecular weight thrombin inhibitor,
      argatroban in association with a well defined thrombolytic agent in a
      reproducible animal model of thrombolysis in vivo. Thrombi were formed in rat
      mesenteric venules with a helium neon (He-Ne) laser in the presence of Evans blue
      and were stabilised for 10 minutes. Thrombi formed in this manner were shown by
      transmission electron microscopy to be composed mainly of platelets. Thrombolysis
      was induced with recombinant staphylokinase in the presence and absence of
      argatroban and the process was monitored using computerised image analysis. Co
      infusion of argatroban at a dose of 2.0 mg/kg/h with staphylokinase significantly
      enhanced the rate of thrombolysis. The results suggested that administration of
      the thrombin inhibitor together with the fibrinolytic agent moderated platelet
      dependent mechanisms and led to a more rapid restoration of blood vessel patency.

PMID- 9175234
TI  - p-Aminobenzoic acid, but not its metabolite p-acetamidobenzoic acid, inhibits
      thrombin induced thromboxane formation in human platelets in a non NSAID like
      manner.
AB  - We have previously shown that p-aminobenzoic acid (PABA) is acetylated by several
      cell lines and most peripheral blood cells, including platelets, to p
      acetamidobenzoic acid (PACBA). The structural similarity of PABA and PACBA to
      local anesthetics and some non steroidal anti inflammatory drugs urged us to
      perform the present investigation. When human platelets were stimulated with
      thrombin to liberate AA, we found that PABA inhibited the production of
      thromboxane (TxB2) as measured with enzyme-linked immunosorbent assay. The
      inhibition was reversible and observed at PABA concentrations ranging between 55
      and 1000 microM. At 328 microM PABA the production of TxB2 diminished by 87% (p =
      0.013). PACBA in the same doses did not affect the production of TxB2. When
      platelets were incubated with [1-14C]AA, in the presence of PABA, the production
      of [1-14C]TxB2 was only slightly inhibited, according to analysis by high
      pressure liquid chromatography. Obviously PABA is not mainly acting as a
      prostaglandin H (cyclooxygenase) or Tx synthase inhibitor. It is rather affecting
      a step prior to thromboxane production, most likely the liberation of the
      precursor AA. In conclusion, our results demonstrate for the first time that
      PABA, a substance occurring in nature, inhibits endogenous TxB2 synthesis in
      human platelets and might thus exert profound effects on platelet AA metabolism.

PMID- 9175235
TI  - Discrepancy between latex and ELISA D-dimer values in sepsis may be caused by
      human neutrophil elastase.
AB  - We have recently shown that D-dimers are degraded by human neutrophil elastase
      (HNE) in vitro, causing rapid decrease in the D-dimer levels measured by a Latex
      test, but not with an ELISA test employing the same monoclonal antibody against D
      dimer. To see if such discrepant D-dimer concentrations occurred in patients with
      high HNE concentration, we examined 80 plasma samples from 8 patients with sepsis
      with a Latex and an ELISA test and calculated the ratio between the D-dimer
      values obtained with the two tests. Twenty healthy pregnant and twenty pre
      eclamptic patients, who are known to have raised D-dimer but low HNE
      concentrations, were chosen as controls. HNE levels were estimated by determining
      the HNE-alpha 1-proteinase inhibitor complex (HNE-A1PI) concentration. HNE-A1PI
      concentration was increased in sepsis patients compared with pre-eclamptic
      patients (p < 0.0005) and healthy pregnant women (p < 0.0005). In sepsis
      patients, the D-dimer results were skewed towards lower ratios between Latex and
      ELISA values compared to pre-eclamptic patients (p = 0.008) and healthy pregnant
      women (p = 0.0001). In plasma samples from patients with the largest discrepancy
      between Latex and ELISA D-dimer values, Western blotting with immunostaining
      indicated degradation of D-dimers to D-like fragments similar to those observed
      following degradation of cross-linked fibrin by HNE in vitro. We conclude that in
      sepsis patients there is a marked discrepancy between Latex and ELISA D-dimer
      values that may be caused by HNE. In such patients Latex D-dimer assays may cause
      severe underestimation of fibrinolysis.

PMID- 9175236
TI  - Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM
      patients.
AB  - Free radical activity may contribute to atherosclerotic lesions which in diabetic
      subjects may frequently lead to vascular complications. It is known that
      oxidative stress is associated to diabetes. Protein glycation and glucose
      oxidation could be possible source of free radicals. 28 non insulin dependent
      diabetic subjects (NIDDM) were examined. 20 healthy subjects matched for age, sex
      and for the presence of hypertension and hyperlipidemia were also studied.
      Hydrogen peroxide, measured by intracellular levels of the fluorescent 2,7
      dichloro-fluorescein (DCF), was considered as indicative parameter of free
      radical production. The results showed that in resting platelets the basal level
      of hydrogen peroxide was significantly higher in diabetic subjects than in
      controls. Moreover, after stimulation with thrombin, collagen, phorbol myristate
      acetate (PMA) and platelet activating factor (PAF), platelets of diabetic
      subjects generated significantly higher amounts of hydrogen peroxide than
      controls. Moreover, platelet aggregation induced by adenosine 5'-diphosphate
      (ADP) and plasma beta TG levels were higher in diabetics than in controls. In
      diabetic patients platelet free radical production and functional activity are
      increased and therefore could play a role in the elevated thrombotic risk
      described in diabetes.

PMID- 9175237
TI  - Relationship between changes in F1+2 and TAT levels and blood coagulation early
      after prosthetic valve replacement.
AB  - Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT), D
      dimer and other coagulation-related factors were measured over time in 48
      patients who underwent prosthetic valve replacement and subsequent anticoagulant
      therapy, in order to evaluate the dynamics of thrombin generation. Before
      surgery, levels of both F1 + 2 and TAT were high, indicating enhanced thrombin
      generation. On the 7th day after initiation of postoperative administration of
      warfarin, F1 + 2 was significantly lower than preoperatively, while TAT tended to
      be increased. Even on the 21st day, levels of both F1 + 2 and TAT were still
      high. Despite the administration of warfarin, thrombin generation increased in
      these patients. After surgery, D-dimer level was increased, indicating
      hyperfibrinolysis. On the 21st day after initiation of warfarin administration,
      abnormally high levels of F1 + 2 were observed in 4 of the 48 patients. In these
      4 patients, thrombin generation was markedly increased, suggesting that they were
      in a preliminary stage of thrombogenesis. Antiplatelet therapy did not affect the
      levels of F1 + 2 or TAT. Our findings suggest that both F1 + 2 and TAT levels are
      useful for evaluation of enhanced coagulability. D-dimer is also considered to be
      useful as a parameter of fibrinolysis. F1 + 2 is less affected by surgical
      invasion than TAT, and therefore appeared to reflect coagulability more
      accurately.

PMID- 9175238
TI  - The association of reduced endothelium derived relaxing factor-NO production with
      endothelial damage and increased in vivo platelet activation in patients with
      diabetes mellitus.
AB  - The role of reduced endothelial production of EDRF-NO in the pathogenesis of
      diabetic angiopathy has received much attention, however, most of the rather
      conflicting data were gained from animal experiments. Limited human experience
      seems to be available in insulin dependent diabetes, calling attention to
      decreased EDRF-NO production. Hereby the clinical, as well as laboratory
      investigation (urinary and serum nitrate/nitrite, lipid peroxidation,
      glucometabolic parameters, endothelial and in vivo platelet activation markers,
      etc.) of 35 non-insulin dependent (NIDDM) and 15 insulin dependent diabetics
      (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were
      proven to be reduced in both patients groups. This change was independent of
      diabetes duration, presence of macroangiopathy, coronary heart disease and the
      glucometabolic parameters, however, correlation was registered with lipid
      peroxidation (total antioxidant status). An inverse correlation of
      nitrate/nitrite excretion with endothelial markers (von Willebrand factor,
      soluble thrombomodulin) was documented in NIDDM, this correlation was much
      stronger in IDDM. Moreover, in IDDM patients reduced nitrate/nitrite excretion
      was strongly associated with elevated plasmatic beta-thromboglobulin levels. The
      data presented here support to the hypothesis, that EDRF-NO production is reduced
      in diabetes and this reduction seems to correlate with endothelial damage. In
      IDDM the decreased nitrate/nitrite excretion may also lead to increased in vivo
      platelet activation, which suggests that the reduced amount of EDRF-NO might play
      a role in the pathogenesis of angiopathy in IDDM.

PMID- 9175239
TI  - Absence of factor V Leiden mutation in Koreans.

PMID- 9175240
TI  - Dietary pectin influences fibrin network structure in hypercholesterolaemic
      subjects.
AB  - Fibrinogen is an important risk factor for atherosclerosis, stroke and
      cardiovascular heart disease (CHD). This risk is increased when associated with a
      high serum cholesterol. Furthermore, it is also believed that not only fibrinogen
      concentration, but also the quality of fibrin networks may be an important risk
      factor for the development of CHD. CHD and stroke as a result of atherosclerosis,
      plus the related problems of hyperinsulinaemia, hyperlipidaemia and hypertension
      are strongly related to diet. The "western" diet, defined by low fibre and high
      fat, sucrose and animal protein intakes, appears to be a major factor leading to
      death. It has been established that the water-soluble dietary fibre, pectin,
      significantly decrease the concentration of serum cholesterol levels. Evidence is
      also accumulating that a diet rich in fibre may protect against diseases
      associated with raised clotting factors. This investigation studied the possible
      effects of pectin on fibrinogen levels and fibrin network architecture. Two
      groups of 10 male hyperlipidaemic volunteers each, received a pectin supplement
      (15 g/day) or placebo (15 g/day) for 4 weeks. Lipid and fibrin network structure
      variables were measured at baseline and the end of supplementation. Pectin
      supplementation caused significant decreases in total cholesterol, low-density
      lipoprotein cholesterol, apolipoprotein A & B and lipoprotein (a). Significant
      changes in the characteristics of fibrin networks developed in the plasma of the
      pectin supplemented group indicated that networks were more permeable and had
      lower tensile strength. These network structures are believed to be less
      atherogenic. It is suspected that pectin modified network characteristics by a
      combination of its effects on metabolism and altered fibrin conversion. This
      confirms the therapeutic possibilities of dietary intervention. Furthermore, this
      study also showed that changes in plasma fibrinogen need not be present to induce
      alterations in fibrin network architecture.

PMID- 9175241
TI  - Protein S deficiency and antibodies to protein S in patients with Behcet's
      disease.
AB  - Thrombosis occurs in 20 to 30% of patients with Behcet's disease (BD). Most of
      the reported hemostatic abnormalities are related to the inflammatory syndrome.
      We have assessed the activity of antithrombin III, protein C and protein S (PS),
      in 30 patients with BD and in 30 healthy controls. Thrombosis antecedents were
      found in 16 patients. Antithrombin III and protein C were within the normal
      range, however free PS and PSactivity were significantly decreased in patients as
      compared to control group. PS deficiency detected in eight patients, was
      associated to thrombosis in 6 of them. No correlation was found between free
      PS/total PS ratio and C4bBP levels. Antibodies to PS were screened by ELISA and
      were present in 6 patients, associated to PS deficiency in 4, and to thrombosis
      antecedents in 5 cases. PS deficiency was transient in two patients, associated
      to a persistent antiPS in one of them. These findings suggest that auto-immune
      acquired PS deficiency may be involved in the pathogenesis of thrombotic events
      in BD.

PMID- 9175242
TI  - Effects of platelets and white blood cells and antiplatelet agent C7E3 (Reopro)
      on a new test of PAF procoagulant activity of whole blood.
AB  - This study was designed to evaluate the effects of varying concentrations of
      platelets, white blood cells (WBC) and Fab fragments of a monoclonal antibody
      (c7E3, Reopro) directed at the platelet GpIIb-IIIa receptor complex on ACT-based
      clot ratio values (hemoSTATUS assay) in healthy volunteers. These measurements
      were made in heparinized whole blood from 10 normal volunteers in which either
      platelet or WBC concentrations had been varied by differential centrifugation. In
      addition, blood collected in either heparin or argatroban was incubated with
      varying concentrations of c7E3 (Reopro). Clot ratio values (%Maximal) in normal
      blood did not decrease until average platelet counts were less than 50,000. A
      marked reduction in clot ratios was observed when WBC concentration increased
      above or decreased below baseline clot ratios within each patient. Strong linear
      relationships were observed between white cell concentration and clot ratio
      values when white cell concentrations were either less or greater than baseline
      values. When argatroban was used as an anticoagulant, inverse relationships were
      demonstrated between clot ratio values and increasing c7E3 concentration (Ch 3: r
      = -0.33, Ch4: r = -0.84, Ch5: r = -0.87, Ch 6: r = -0.71). ACT-based clot ratio
      values determined in heparinized whole blood presumably reflecting PAF inducible
      platelet procoagulant activity, are affected by platelet concentration when
      counts are less than 50,000/microliter. The hemoSTATUS test was also found to be
      affected by WBC concentration since clot ratio values decreased when WBC counts
      were below 4,000/microliter or above 9,000/microliter. A dose-dependent reduction
      in clot ratio values was also observed with increasing concentrations of c7E3.
      This test can reliably detect platelet dysfunction only if the platelet count is
      > 50,000 and the WBC is normal.

PMID- 9175243
TI  - Biological matrix-dependent pharmacokinetic and pharmacodynamic parameters of a
      novel platelet glycoprotein IIB/IIIA receptor antagonist, XU063, in beagle dogs.
AB  - The pharmacokinetic-pharmacodynamic (PK/PD) relationship of a novel platelet
      glycoprotein IIb/IIIa receptor antagonist, XU063, was evaluated as a function of
      biological matrix in beagle dogs. The disposition of 14C-radioactivity in various
      blood or plasma matrices and kinetics of inhibition of adenosine diphosphate
      (ADP) induced platelet aggregation were determined in beagle dogs following an
      intravenous infusion of 14C-XU063 at 2 micrograms/kg for 45 min. The 14C
      radioactivity was maximum in platelet poor plasma (PPP) harvested from blood
      collected in EDTA and lowest in PPP harvested from blood collected in citrated
      vacutainers over the entire concentration versus time profile during and post
      infusion. The 14C-radioactivity values in blood and platelet rich plasma (PRP)
      were comparable and were between EDTA PPP and citrated PPP values. The resultant
      estimates of the PK and PD parameters of 14C-XU063 varied widely depending on the
      type of matrix used. The systemic clearance values for 14C-XU063 were 1 and 10
      mL/min/kg for EDTA and citrated PPP, respectively. The values for the volume of
      distribution at steady-state were 0.2 and 1.3 L/kg, for EDTA and citrated PPP,
      respectively. The terminal elimination half-life appeared independent of the
      matrix with a median value of 2 h. The estimated ex vivo IC50 values of XU063
      ranged from 0.4 ng/mL (citrated PPP, platelet free drug) to 7 ng/mL (EDTA PPP,
      total drug). These results demonstrated the dependence of PK and PD parameters of
      antiplatelet agent XU063 on the type of biological matrix used to determine
      concentrations of XU063. The pros and cons of various blood sample collection
      methods for the evaluation of PK/PD relationship of potential antiplatelet agents
      are presented.

PMID- 9175244
TI  - Further characterization and thrombolytic activity in a rat model of a
      fibrinogenase from Vipera lebetina venom.
AB  - Vipera lebetina fibrinogenase (VlF) was shown to render fibrinogen incoagulable
      and to solubilize fibrin. The fibrinogenolytic activity of this enzyme was found
      to be 33 mg fibrinogen/min/mg protein. The study of the specificity of this
      enzyme revealed that it has no effect on purified factor X, prothrombin and
      protein C and on the specific chromogenic substrates of their active form.
      Plasminogen was not activated by VlF but slightly degraded. We have also compared
      the effect of VlF and plasmin on fibrinogen and shown that these two enzymes have
      a different sites of cleavage. This enzyme inhibited human platelet aggregation
      on PRP initiated by ADP and collagen but was without effect on the aggregation of
      washed rabbit platelets using thrombin as agonist. Administration of VlF in rat
      did not show any necrosis or hemorrhage in treated rats organ's. We therefore,
      examined the thrombolytic activity of VlF in a rat model of venous thrombosis.
      Thrombus was produced in the posterior vena cava by injection of human fibrinogen
      and thrombin. Injection of 5 mg/Kg body weight showed an evident flow restoration
      after one hour and measurement of the fibrinogen level a decrease of about 30%
      after 3 hrs. VlF's action is not dependent on plasminogen activators and may act
      synergistically with them, thereby providing an intriguing potential clinical
      application for dissolution of blood clots.

PMID- 9175245
TI  - Proinflammatory activity on rat carotid endothelium of albumins obtained by
      different procedures.
AB  - To investigate whether the proinflammatory activity of intravenously administered
      albumins is related to their preparation method, we compared bovine albumins
      obtained by alcohol precipitation and by heat shock. This last procedure produced
      a notable increase in monocyte adhesion/mm2 in rat carotid endothelium (48 +/-
      31, n = 32 rats, vs 7 +/- 6, n = 24 rats, mean +/- S.D., P < 0.001). We found no
      changes in fluorescence emission in these two groups, and no correlation was
      observed between leukocyte adhesion and the contents of free fatty acids, free 
      SH groups, fructosamine, dimers and polymers. The inhibition profile of the
      proinflammatory activity by polyanionic molecules (fucoidan and dextran sulfate
      500 kD) was compatible with the recognition of heat-shocked albumins by scavenger
      receptors. Thiol disulfide exchange in albumins was produced by ageing with
      cysteine and by incubation with protein disulfide isomerase. Albumins thus
      modified increased the adhesion of leukocytes to the endothelium, which indicates
      that some isomeric forms of albumin generated by thiol disulfide exchange may
      acquire proinflammatory behavior.

PMID- 9175246
TI  - Platelet aggregation by IgG anti-streptokinase and anisoylated plasminogen
      streptokinase activator complex: heterogenous responses in platelet-rich plasma
      but not in washed platelets.

PMID- 9175247
TI  - Fibrinopeptide A release from intraplatelet fibrinogen is related to thrombin
      platelet activation.

PMID- 9175248
TI  - Antithrombotic prophylaxis in patients undergoing laparoscopic cholecystectomy.

PMID- 9175250
TI  - Clustering of haemagglutinin gene sequences of measles viruses isolated in the
      Gambia.
AB  - Partial nucleotide sequences of the haemagglutinin (H) gene of 18 measles viruses
      isolated in the Gambia during 1994 and 1995 show a high degree of homology (>
      98.5%) when compared with each other. These sequences form a cluster distinct
      from measles viruses isolated from other geographic regions and from the
      sequences of vaccine strains and two isolates from the Gambia from earlier years.
      Despite the low level of genetic heterogeneity observed, a common feature of the
      Gambian isolates is the presence of three nucleotide changes (at positions 7963,
      8649 and 8653) not observed in isolates from other locations.

PMID- 9175249
TI  - Characterization and expression of the Marek's disease virus serotype 2
      glycoprotein E in recombinant baculovirus-infected cells: initial analysis of its
      DNA sequence and antigenic properties.
AB  - In Marek's disease virus (MDV) serotype 2 (MDV2) genome, a gene equivalent to the
      glycoprotein E (gE) of other alphaherpesviruses was identified and sequenced. The
      primary translation product comprises 488 amino acids with a M(r) of 54.3 kDa.
      The predicted amino acid sequence possesses several characteristics typical of
      membrane glycoproteins, including a N-terminal hydrophobic signal sequence, C
      terminal transmembrane and cytoplasmic domains, and extra-cellular region
      containing four potential N-linked glycosylation sites. Compared with other MDV
      serotypes, MDV2 gE showed 47.3% identity with MDV1 gE, and 38.9% identity with
      HVT gE at the amino acid level. In transcriptional analyses, a 2.0 kb mRNA which
      starts between 65 and 86 bps upstream of the potential translational initiation
      codon of gE was identified as the gE-specific transcript. By a recombinant
      baculovirus, this potential gE coding region was expressed as several specific
      products from 66 to 72 kDa. These products were susceptible to tunicamycin
      treatment, indicating that they were glycoprotein in nature. Further, the
      expressed gE reacted with all chicken-antisera raised to each of the three
      serotypes of MDV (strains GA, SB-1, and FC126), suggesting that gE is expressed
      by all three serotypes of MDV in infected cells and conserves common antigenic
      epitope(s) beyond those that are serotype specific.

PMID- 9175251
TI  - Distribution of Mayaro virus RNA in polysomes during heat shock.
AB  - Mayaro virus (alphavirus) infection of Aedes albopictus cells results in
      inhibition of cell protein synthesis and viral proteins are preferably
      synthesized. When infected cells are heat shocked, however, there is also an
      inhibition of viral protein synthesis, and there is preferential synthesis of
      heat shock proteins. Based on these observations, the distribution of Mayaro
      viral RNA in polysomes and the association of p34 (capsid protein) with ribosomal
      fractions of the cells under such conditions have been analyzed. During
      infection, the viral RNA is mainly observed in light polysomes (60% of total
      viral RNA in the cell) and also in heavy polysomes (13%). However, when infected
      cells are heat-shocked, the viral RNA is strongly mobilized from heavy polysomes
      to the light polysomes fraction and an enrichment in the unbound fraction can be
      noticed. The amount of p34 associated with the ribosomal fraction was also shown
      to be decreased in the heat shocked cells. These data lead to the suggestion that
      two mechanisms could be involved in the inhibition of Mayaro virus protein
      synthesis in response to heat shock: (1) mobilization of Mayaro virus RNA from
      heavy to light polysomes; (2) a decrease in the amount of the p34 within the
      ribosomal fraction.

PMID- 9175252
TI  - Evidence that fatal human infections with La Crosse virus may be associated with
      a narrow range of genotypes.
AB  - La Crosse (LAC) virus belongs to the California (CAL) serogroup of the genus
      Bunyavirus, family Bunyaviridae. It is considered one of the most important
      mosquito-borne pathogens in North America, especially in the upper Mid-West,
      where it is associated with encephalitis during the time of year when mosquitoes
      are active. Infections occur most frequently in children and young adults and,
      while most cases are resolved after a period of intense illness, a small fraction
      (< 1%) are fatal. At present there have only been three isolates of LAC virus
      from humans all made from brain tissue postmortem. The cases yielding viruses are
      separated chronologically by 33 years and geographically from Minnesota/Wisconsin
      (1960, 1978) to Missouri (1993). The M RNA sequence of the first two isolates was
      previously reported. The present study extends the observations to the isolate
      from the 1993 case and includes several mosquito isolates as well. A comparison
      of the M RNAs of these viruses shows that for the human isolates both nucleotide
      sequence and the deduced amino-acid sequence of the encoded proteins are highly
      conserved, showing a maximum variation of only 0.91% and 0.69%, respectively.
      This high degree of conservation over time and space leads to the hypothesis that
      human infections with this particular genotype of LAC virus are those most likely
      to have a fatal outcome. It is also shown that a virus with this genotype could
      be found circulating in mosquitoes in an area more or less intermediate between
      the locations of the first and second fatal cases.

PMID- 9175253
TI  - Chinese hamster ovary cells are non-permissive towards infection with
      coxsackievirus B3 despite functional virus-receptor interactions.
AB  - Viral infection is a complex process which includes binding and interaction of
      the virus with specific cell surface receptors, uptake and uncoating of the
      virus, and finally replication. Chinese hamster ovary (CHO) cells are non
      permissive towards infection with coxsackieviruses of group B (CVB), although
      they do express a putative CVB-specific receptor protein. In order to localize
      the block of infection in CHO cells, these cells were tested for binding of
      radiolabelled CVB3, receptor-mediated transformation of virions into A-particles,
      and replication of the viral genome. Binding of CVB3 to CHO cells was found to be
      comparable to the binding of this virus to permissive cell lines. Detergent
      solubilized membrane proteins of CHO cells were tested in virus overlay protein
      binding assays (VOPBAs) and shown to express a 100 kDa CVB-binding membrane
      protein similar to the CVB receptor protein which we recently described for
      permissive HeLa cells. Incubation of CVB3 with intact CHO cells resulted in
      transformation of cell-bound virions into non-infectious A-particles (deprived of
      capsid protein VP4), demonstrating the functional activity of the CVB receptor
      protein on CHO hamster cells. Transfection of recombinant CVB3 cDNA or viral RNA
      into CHO cells resulted in the production of infectious CVB3 virions, implying
      that the failure of CVB to infect CHO cells is not caused by a defect in virus
      replication but results from a block in the uptake of virus particles into the
      cell after the initial steps of virus-receptor interactions.

PMID- 9175254
TI  - Characteristic in vitro evolution pattern of foot and mouth disease virus
      A81/Castellanos/Arg/87.
AB  - The in vitro evolution of Foot and mouth disease virus (FMDV)
      A/81/Castellanos/Arg/87 (A/Castellanos/87) was studied by partial biological and
      biochemical characterization of viral populations selected after 25 passages on
      secondary fetal bovine kidney cell monolayers. These passages were performed in
      the presence or absence of immune pressure exerted in the form of antiviral
      polyclonal serum. While the viral populations passaged in the absence of immune
      pressure acquired characteristics such as antigenic heterogeneity, VP1 amino acid
      modification and plaque size reduction, the populations selected after immune
      pressure also presented both neutralizing resistance and attenuation for suckling
      mice. The comparison with other previously studied FMDV strains suggests that
      FMDV A/Castellanos/87 adopts a differential response to immunological pressure
      and other selective forces. In addition, the sequencing analysis of viral
      selected populations shows a restriction in the number and type of amino acid
      replacements tolerated by FMDV capsid proteins.

PMID- 9175255
TI  - Analysis of the haemagglutinin gene of current wild-type canine distemper virus
      isolates from Germany.
AB  - The haemagglutinin (H) gene sequences from three wild-type canine distemper
      viruses (CDV) isolated during 1994-1995 were sequenced to determine whether
      contemporary strains had undergone significant genetic changes relative to the
      currently used vaccine strains. The new isolates were closely related to each
      other (> 99%) and displayed about 90-91% sequence homology to the Onderstepoort
      and Convac vaccine strains. There were one to four additional potential
      glycosylation sites compared to the vaccine strains which were also present in a
      German dog CDV isolate dating from 1990. However, only a very slight reduction in
      neutralizing titre against the new isolates was found when compared with the
      Onderstepoort and Rockborn vaccine strains. Cysteine and proline residues were
      well conserved indicating a conserved three dimensional structure for the
      protein. By phylogenetic analysis the recent isolates showed a narrow clustering
      close to the previous canine isolates indicating a linear pattern of evolutionary
      changes. A comparison with published CDV H gene sequences suggested the presence
      of different lineages of CDV on a global scale and possible cocirculation of more
      than one genotype of CDV.

PMID- 9175256
TI  - Intracellular thiol redox status affects rat cytomegalovirus infection of
      vascular cells.
AB  - There is increasing evidence for cytomegalovirus (CMV) induced vascular pathology
      during acute infection in the immunocompromised host. Inflammation is involved in
      such processes, which is frequently associated with increased levels of oxidative
      mediators and reduced anti-oxidant protection. A relation between viral infection
      and oxidative stress has been recognized for human immunodeficiency virus and
      herpes simplex virus-1 infections, but little is known in this respect for CMV
      infections. We investigated if there is a relation between CMV infection of
      vascular cells and the intracellular redox status using an in vitro rat model. We
      measured intracellular glutathione levels and rat CMV (RCMV) permissiveness of
      rat heart endothelial cell lines (RHEC), rat smooth muscle cells (RSMC), and
      compared these with fully CMV-permissive rat fibroblasts (REF and Rat 2). In
      addition, the effects of the anti-oxidant N-acetylcysteine (NAC) and the
      glutathione synthesis inhibitor buthionine sulfoximide (BSO) on CMV
      permissiveness and replication were investigated in these cell lines. Finally, we
      investigated infection of vascular cells under inflammatory conditions in an in
      vivo rat model for acute CMV infection. The results show a very high endogenous
      glutathione level in RHEC compared to REF, Rat 2 cells and RSMC. This is
      associated with a low CMV permissiveness in RHEC as opposed to full
      permissiveness in REF, Rat 2 cells and RSMC in vitro. In addition, modulation of
      the intracellular thiol redox status affected CMV infection and replication only
      in RHEC, but not in RSMC and Rat 2 cells. During acute infection in vivo under
      immunosuppressed conditions rat endothelial cells first become activated and
      subsequently infected leading to vascular damage and pathology. This study
      suggests that a high endogenous thiol redox status may contribute to the apparent
      barrier function of endothelial cells with respect of CMV infection and that
      oxidative stress may facilitate CMV infection of the vascular wall.

PMID- 9175257
TI  - GB virus C/hepatitis G virus infection among Korean patients with liver diseases
      and general population.
AB  - GB virus C and hepatitis G virus (GBV-C/HGV) have been identified from the
      patients with acute or chronic liver diseases as possible agents of non-B, non-C
      hepatitis by two different groups, independently. To investigate whether GBV
      C/HGV plays a role among Korean patients with liver diseases, GBV-C/HGV RNA were
      evaluated in 337 sera by the reverse transcription polymerase chain reaction (RT
      PCR) using specific primers derived from 5'-noncoding region of GBV-C/HGV genome.
      GBV-C/HGV RNA was identified in 11/337 (3.3%). They consisted of 1/160 (0.6%) and
      10/177 (3.3%) among the general population and patients with liver diseases,
      respectively (P < 0.01). Nucleotide sequences of all PCR amplicons were
      determined by the dideoxy chain termination method and analyzed by molecular
      evolutionary methods. The phylogenetic tree showed all sequences could be divided
      into three genotypes. These results indicate that: (1) GBV-C/HGV already exist in
      Korea; (2) GBV-C/HGV may play some role as an etiologic factor among the Korean
      patients with liver diseases; (3) GBV-C/HGV infection is rare among Korean
      general population; and (4) there are at least three different types of GBV-C/HGV
      in Korea.

PMID- 9175259
TI  - Activation of protein kinase C enhances the infection of endothelial cells by
      human cytomegalovirus.
AB  - The infection of cultured endothelial cells with human cytomegalovirus (HCMV) is
      generally limited to less than 10% of the cells in contrast to HCMV infection of
      fibroblasts, where essentially all cells can be infected. It is known that HCMV
      infection influences a number of signal transduction pathways of infected cells.
      We therefore questioned whether, conversely, the infectivity of human umbilical
      vein endothelial cells could be influenced by the deliberate activation of these
      pathways. When endothelial cells were treated prior to infection with phorbol
      myristoyl acetate, an activator of protein kinase C, the number of HCMV-positive
      cells increased two to three times. On the other hand, pretreatment of the cells
      with RO 31-8220, a specific protein kinase C inhibitor, or with staurosporine, a
      general protein kinase inhibitor, resulted in a decreased infection level and in
      abolishment of the PMA-induced effect. Pretreatment with the protein phosphatase
      inhibitor, okadaic acid, caused a slight increase in infectivity, whereas
      pretreatment with the protein tyrosine kinase inhibitor, genistein, was without
      effect. Furthermore, neither forskolin and ilomedine, compounds known to activate
      the endothelial adenylate cyclase, nor the calcium ionophore A23187 were able to
      influence HCMV infectivity. It is concluded that: (a) the HCMV infection level of
      unstimulated endothelial cells is influenced by the basal level of protein kinase
      C; and (b) stimulation of protein kinase C prior to infection results in an
      increase of infection by HCMV.

PMID- 9175258
TI  - Genetic and antigenic heterogeneity among feline calicivirus isolates from
      distinct disease manifestations.
AB  - The capsid protein genes of five feline calicivirus (FCV) isolates associated
      with different disease manifestations were cloned and sequenced. The viruses
      represented two recent isolates from cats with chronic stomatitis, one recent
      isolate from a cat with acute stomatitis, one recent isolate each from a cat with
      acute respiratory symptoms and the classical limping syndrome strain FCV-2280.
      The amino acid sequences were compared with eight other published sequences and
      analyzed for their relationships. Phylogenetic analysis of the complete capsid
      protein sequences or of known antigenic regions of that protein (hypervariable
      regions A and E) did not group the isolates of different disease manifestations
      in distinct subclusters. Monoclonal antibodies (MAbs) generated against either a
      chronic stomatitis isolate or a recent isolate associated with respiratory
      symptoms were tested against a panel of 11 recent isolates and four "classical'
      FCV strains, covering all known disease associations. With those MAbs no obvious
      clustering with respect to disease manifestation could be seen. Four specific
      sera prepared in rabbits against our prototype isolates also failed to cluster
      those isolates according to the disease manifestations when examined in
      neutralization tests. From these antigenic and genetic analyses of the capsid
      protein the hypothesis of the existence of biotypes of FCV responsible for
      distinct disease manifestations could not be confirmed.

PMID- 9175260
TI  - Polarized dispersion of X-rays in pyrite.
AB  - Diffraction of synchrotron radiation in a crystal of FeS2 reveals dipolar
      anisotropy of anomalous scattering by Fe near its K-absorption edge, in spite of
      the almost-regular octahedral geometry of the nearest S neighbors. At 7121 eV,
      the magnitude of f changes with polarization direction by as much as 0.7 electron
      units. No effects of quadrupolar anisotropy were detected.

PMID- 9175261
TI  - The accurate electron crystallographic refinement of organic structures
      containing heavy atoms.
AB  - Prospects for the accurate structure determination of heavy-atom-containing
      organic crystals were evaluated with electron diffraction data from perchloro and
      perbromo derivatives of copper phthalocyanine. While the extensive overlap of
      experimental Patterson maps (from 1200kV intensities) with respective crystal
      autocorrelation functions explains the success of previous direct structure
      analyses, it is clear that multiple-scattering perturbations still evident at
      high voltage will frustrate the determination of accurate bond distances and
      angles. If, however, the result obtained after direct structure analysis and
      Fourier refinement is used to position an idealized molecular model (i.e. with
      chemically reasonable bonding parameters), the correct structure can then be
      justified by a rotational search coupled with a multislice dynamical calculation.
      Even though dynamical scattering is not the only major perturbation to such data
      sets, the resolution-limited correction is still sufficient to identify the
      correct molecular orientation in the unit cell. Alternatively, an acceptable
      unconstrained structure refinement can be carried out via a procedure proposed by
      Huang, Liu, Gu, Xiong, Fan & Li [Acta Cryst. (1996), A52, 152-157]. A
      phenomenological adjustment of observed intensities, based initially on the heavy
      atom positions found in a high-resolution electron micrograph, will permit all
      light atoms to be observed near their ideal positions in the ensuing Fourier
      refinement.

PMID- 9175262
TI  - News and views on the nucleolus in 1996. Report on the 'Colloquium on the
      nucleolus', a meeting at Paris-Grignon, July 18-20, 1996.
AB  - The new data presented by the participants during the 'Colloquium on the
      Nucleolus' were reviewed and regrouped in different topics concerning the
      molecular and functional significance of nucleolar structure. The topics
      included: rRNA transcription and nucleolar organization, the nucleolus in
      relation to cell proliferation including nucleolus in pathology during the cell
      cycle and cell division, nucleologenesis, and nucleolar proteins.

PMID- 9175263
TI  - Apoptosis-induced concomitant release of cytosolic proteins and factors which
      prevent cell death.
AB  - In the course of the apoptotic cell death, cells fragment into apoptotic bodies,
      the elimination of which by phagocytosis is thought to avoid the release of
      cytosolic constituents whose occurrence is indicative for necrotic cell death.
      Confluent cultures of chicken embryo fibroblasts, however, show a different
      behaviour. After serum deprivation, they transiently released with the same time
      course mitogenic activity, lactate dehydrogenase and cytosolic peptidyl prolyl
      cis-trans isomerases into the serum-free culture medium. The release correlated
      in time with a decrease of the cell number which started approximately 3 h after
      serum removal and ceased within approximately 10 h at about half of the initial
      cell density. Morphological features like cell shrinkage, membrane blebbing and
      cell fragmentation as well as internucleosomal DNA fragmentation indicated
      apoptotic cell death whereas necrotic cell death could be excluded. Conditioned
      medium (M(r) > or = 30 kDa) from serum-deprived cultures of chicken embryo
      fibroblasts completely prevented chicken embryo fibroblasts to undergo apoptosis
      as did phorbol 12-myristate, 13-acetate and, to -60%, L-cysteine. Cycloheximide
      had no effect on serum deprivation-induced apoptosis. From the present results it
      can be concluded that chicken embryo fibroblasts and possibly other cells
      undergoing apoptosis release cytosolic components and endogenous survival
      factor(s) which prevent apoptosis.

PMID- 9175264
TI  - The motility and fertility of golden hamster sperm cultured in BSA-free medium.
AB  - Before fertilization, capacitation and the acrosome reaction in mammalian
      spermatozoa must be completed. The motility and fertility of hamster sperm were
      examined in four kinds of modified Tyrode's solution with or without bovine serum
      albumin (BSA). Since the presence or absence of polyvinylalcohol (PVA) in the
      media was another variable, its effect on the sperm motility and fertility was
      also studied. Sperm were incubated in four different media for up to 6 h at 37.5
      degrees C. After 4 h of incubation in the media containing BSA alone or BSA and
      PVA, sperm were hyperactivated, showing a high sperm motility index (SMI) and
      were able to fertilize more than 80% of eggs. However, their fertility rapidly
      decreased during further incubation. In contrast, sperm in the medium containing
      PVA and no BSA showed low SMI scores after 4 h. However, during the following 2-h
      period, the SMI progressively increased and sperm were hyperactivated.
      Furthermore, the hyperactivated sperm in the PVA containing medium were able to
      effectively fertilize eggs. Our results indicate that hamster sperm can be
      capacitated in BSA-free medium and that capacitation occurs much more slowly in
      such a medium. We suggest that PVA is a reasonable alternative to BSA in in vitro
      fertilization and that this slowly progressing system may be a good model for
      studying various steps in sperm activation.

PMID- 9175265
TI  - Actin cytoskeleton demonstration in Trichomonas vaginalis and in other
      trichomonads.
AB  - The flagellate form of Trichomonas vaginalis (T v) transforms to amoeboid cells
      upon adherence to converslips. They grow and their nuclei divide without
      undergoing cytokinesis, yielding giant cells and a monolayer of T v F-actin was
      demonstrated in Trichomonas vaginalis by fluorescence microscopy using phalloidin
      and an anti-actin mAb which labelled the cytoplasm of both the flagellate and
      amoeboid forms. Comparative electrophoresis and immunoblotting established that
      the actin band has the same 42 kDa as muscle actin, but 2-D electrophoresis
      resolved the actin band into four spots; the two major spots observed were
      superimposable with major muscle actin isoforms. Electron microscopy demonstrated
      an ectoplasmic microfibrillar layer along the adhesion zone of amoeboid T v
      adhering to coverslips. Immunogold staining, using anti-actin monoclonal
      antibodies demonstrated that this layer was mainly composed of actin
      microfilaments. A comparative immunoblotting study comprising seven trichomonad
      species showed that all trichomonads studied expressed actin. The mAb Sigma A
      4700 specific for an epitope on the actin C-terminal sequence labelled only actin
      of Trichomonas vaginalis, Tetratrichomonas gallinarum. Trichomitus batrachorum
      and Hypotrichomonas acosta, but not the actin of Tritrichomonas foetus,
      Tritrichomonas augusta and Monocercomonas sp. This discrimination between a
      'trichomonas branch' and a 'tritrichomonas branch' is congruent with inferred
      sequence phylogeny from SSu rRNA and with classical phylogeny of trichomonads.

PMID- 9175266
TI  - Type IV collagen in sponges, the missing link in basement membrane ubiquity.
AB  - Basement membrane structures, or their main component, type IV collagen, have
      been detected in all multicellular animal species, except sponges. We cancel this
      exception by the demonstration of type IV collagenous sequences in a new marine
      sponge species by cDNA and genomic DNA studies. One of these sequences is long
      enough to demonstrate the specific characteristics of type IV collagen chains.
      The 12 cysteines are at conserved positions in the carboxyl-terminal non-helical
      NCl domain, as are the interruptions in the carboxyl-terminal end of the triple
      helical domain. The gene organization of the region coding for the NCl domain is
      similar to that of the human genes COL4A2, COL4A4 and COL4A6. An additional,
      shorter sequence suggests the presence of a second chain. The expected tissue
      localization of this collagen has been confirmed using polyclonal antibodies
      raised against a sponge recombinant protein. These results demonstrate that type
      IV collagen is representated in all animal phyla. It is actually the only known
      ubiquitous collagen and it has at least two different alpha chains in all the
      species where it has been characterized.

PMID- 9175267
TI  - A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons:
      hippocampal behavior under stress.
AB  - Protein tyrosine kinases play important roles in the development of the mammalian
      nervous system during embryogenesis and in the maintenance of function of the
      adult brain. Using a semi-nested PCR technique based on a short amino acid motif
      of protein tyrosine kinases, we isolated a human genomic DNA encoding a peptide
      whose sequence was related to known mammalian protein tyrosine kinases. The
      expression was examined by Northern blot analysis, and transcripts were detected
      almost exclusively in the brain. The corresponding cDNA was sequenced, and it was
      revealed that the gene designated as byk coded for a receptor-like molecule with
      a motif of protein tyrosine kinase. Immunohistochemical analysis demonstrated
      that the Byk protein was expressed in neurons and was located in the nuclear
      envelope. To understand the physiological significance of the Byk protein, we
      investigated the behavior of this molecule in the hippocampus after ischemia. Byk
      like immunoreactivity disappeared from the neurons in the fields CA1 through CA3
      and the dentate gyrus of the hippocampus following 20 min of ischemia. After
      recirculation of blood flow, neurons in the CA3 field and the dentate gyrus re
      expressed Byk-like antigen but CA1 neurons did not. Interestingly, Byk-like
      immunoreactivity was detected in microglial cells and astrocytes in the CA1 field
      that were activated after ischemia. Byk could be a new tool to study the neuron
      glia and glia-glia interactions.

PMID- 9175268
TI  - Synaptotagmin II expression partially rescues the growth defect of the yeast
      sec15 secretory mutant.
AB  - Synaptotagmins are a family of calcium- and phospholipid-binding proteins
      implicated in the function of cell exocytosis. Synaptotagmins I and II are
      neurally expressed proteins thought to be involved in neurotransmitter release
      from neurons. We have expressed rat synaptotagmin II in several Saccharomyces
      cerevisiae temperature-sensitive secretory mutants that are defective in Golgi to
      plasma membrane vesicular transport. Synaptotagmin II expression was able to
      partially rescue the growth defect in one particular mutant, sec15. No
      suppression was observed when synaptotagmin II was expressed in sec1, sec2, sec4,
      sec5, sec6, sec8, sec9, sec14, sec17, or sec18. Two synaptotagmin II deletion
      mutants were also expressed in sec15 and screened for suppression. The expression
      of the cytoplasmic domain of synaptotagmin alone was not able to suppress the
      sec15 growth defect. In addition, the expression of a synaptotagmin II fragment
      lacking the second half of the cytoplasmic domain including the second C2 domain
      did not suppress sec15. We have isolated a membrane fraction enriched in post
      Golgi vesicles from a sec15 strain expressing synaptotagmin II and found that
      synaptotagmin II co-purifies with this fraction, suggesting that the rat
      synaptotagmin II is targeted to membranes in yeast. Sec15p forms a large
      multisubunit protein complex that includes Sec6p and Sec8p. This protein complex
      is thought to function in a late stage of exocytosis in yeast. Sec6p and Sec8p
      homologs have been identified in mammalian cells. Our studies suggest that
      synaptotagmin may be a part of this complex or regulate its function in mammalian
      cells.

PMID- 9175269
TI  - Ion-water and water-water interactions in a gramicidinlike channel: effects due
      to group polarizability and backbone flexibility.
AB  - In the gramicidin channel, ionic transport and water transport occur
      simultaneously. Gramicidin's transport properties are influenced by ionic
      interactions with both the polypeptide and the channel waters. We present results
      of molecular dynamics studies on a series of alkali metal ions interacting with a
      water-filled gramicidinlike channel (a configurationally constrained polyglycine
      analog) at the dimer junction, in mid-monomer, and near the channel entrance. We
      investigate details of both short and long range ion-water and water-water
      correlation; these are notably dependent on the explicit consideration of
      polarizability and the degree of backbone flexibility. The nature of ion-water
      and water-water correlations changes as ionic size decreases and these changes
      may be augmented or attenuated by manipulation of the two parameters under study.
      Incorporating polarizability generally shortens ion-water distances and enhances
      ion-induced electrostriction (decreased water-water separations), while
      simultaneously reducing the long range orientational correlation of the single
      filing waters within the channel. Increasing flexibility predictably results in a
      broadening of the distribution of water-water and ion-water separations and
      contributes to the loss of long range orientational correlations. Both effects
      are ion specific; Cs+ and Na+ interact with the channel in distinctly different
      ways, while K+ represents an intermediate case more closely resembling Cs+. Our
      results demonstrate that incorporation of polarizability in the potential
      function has significant effects on the properties of channel water and,
      consequently, on the ionic transport process. While ion-water and water-water
      distances are decreased due to this feature, thereby fostering longer ranged
      correlations within the channel, enhanced interactions between water molecules
      and peptide groups tend to mitigate this effect. Possible implications for the
      multiple occupancy states of gramicidin and long range information transfer via a
      single file water chain are considered.

PMID- 9175270
TI  - Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein
      phosphatase 2A.
AB  - (-)-Epigallocatechin gallate (EGCG) was reported to inhibit protein kinase C
      (PKC) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA), and inhibit
      interaction of tumor promoter with its receptors, named 'a sealing effect'. In
      order to clarify the sealing effect of EGCG, we prepared liposomes and examined
      inhibition of PKC activation by various concentrations of EGCG dispersed in the
      liposome. EGCG added to a liposome dispersion existed either in a buffer solution
      as aggregates or in phospholipid bilayer membranes, and EGCG disturbed membrane
      structure. The potency of inhibitory effect of EGCG on PKC activation was
      dependent on the nature of liposomes, indicating that interaction of EGCG with
      phospholipid bilayer membrane affects PKC activation. Moreover, EGCG prevented
      the binding of adenosine 5'-triphosphate and TPA to PKC, resulting in inhibition
      of PKC activation. On the other hand, the activity of protein phosphatase 2A
      (PP2A) was suppressed in the presence of liposomes, but was not influenced by
      EGCG. Moreover, EGCG recovered phosphatase activity of PP2A in a buffer solution,
      the activity of which was inhibited by okadaic acid. All the results indicated
      that EGCG possesses sealing effects in terms of PKC and PP2A, by inhibiting
      interaction of various ligands with proteins.

PMID- 9175271
TI  - Equilibrium and non-equilibrium conformations of peptides in lipid bilayers.
AB  - A synthetic, hydrophobic, 27-amino-acid-residue peptide 'K27', modelled on the
      trans-membrane domain of the slow voltage-gated potassium channel, IsK, has been
      incorporated into a lipid bilayer and its conformational properties studied using
      FT-IR spectroscopy. The conformation following reconstitution is found to be
      dependent on the nature of the solvent employed. When the reconstitution is
      conducted by solvent evaporation from a methanol solution, aggregates comprised
      of beta-strands are stabilised and their concentration is essentially invariant
      with time. By contrast, when trifluoroethanol is used, the initial conformation
      of the peptide is alpha-helical. This then relaxes to an equilibrium state
      between alpha-helices and beta-strands. The alpha-helix-to beta-strand conversion
      rate is relatively slow, and this allows the kinetics to be studied by FT-IR
      spectroscopy. The reverse process is much slower but again can be demonstrated by
      FT-IR. Thus, it appears that a true equilibrium structure can only be achieved by
      starting with peptide in the alpha-helical conformation. We believe this result
      should be of general validity for hydrophobic peptide reconstitution. The
      implications for conformational changes in membrane proteins are discussed.

PMID- 9175272
TI  - Stereoselective syntheses of the O,N-protected subunits of the tunicamycins.
AB  - The synthesis of the title compounds is described, i.e. coupling of the ylide,
      generated from the iodophosphonium salt of protected N-phthaloyl-D-galactosamine
      with 2,3-O-isopropylidene D-ribo-aldehyde afforded an undecose in high yield.
      Hydroboration-oxidation reaction of the olefinic linkage in the undecose led to
      the desired tunicamine, as the predominant product. After conversion of the
      latter to a glycosyl acceptor, this was assembled with the fully protected 2
      oxyimino-2-deoxy-alpha-D-arabino-hexopyranosyl bromide, leading to a trehalose
      type alpha, beta-disaccharide.

PMID- 9175273
TI  - Critical conditions for separating the microheterogeneous components of
      glycoproteins by capillary electrophoresis.
AB  - To separate the microheterogeneous components of glycoproteins, capillary
      electrophoresis (CE) conditions were systematically investigated with ovalbumin
      from chicken egg white as the main testing sample. In addition to the well-known
      adsorption effect, a reversible capillary wall partitioning effect was found to
      contribute greatly to the separation and the favorable lubing wall was that
      coated with polyacrylamide. The separation media, especially the buffer
      composition, its concentration and pH, were also found to be critical. Buffers
      composed of boric acid and alcohol amines were demonstrated to be more effective
      media than gels and other solutions, but the selection of the buffer
      concentrations and pH was dependent on samples. By using free-solution CE with
      polyacrylamide-coated capillaries and boric acid-alcohol amine (BA) buffers,
      ovalbumin of agarose electrophoresis purity can be split into more than twenty
      peaks at pH 8.0 +/- 0.3 (0.2-0.4 mol/l BA). In contrast, free-solution CE with
      uncoated capillaries and gel electrophoresis with polyacrylamide-filled
      capillaries yielded only five or less peaks.

PMID- 9175274
TI  - Capillary electrophoretic analysis of genetic variants of milk proteins from
      different species.
AB  - Polymorphism of bovine, ovine and caprine milk proteins was studied by CE.
      Identification of some rare bovine variants was carried out by isoelectric
      focussing (IEF) using PhastSystem. Genetic variants A and D of bovine alpha s2
      casein, beta-casein variants A1, A2, A3, B and C and alpha s1-casein variants B
      and C were determined by CE. In addition, the different casein fractions
      including some genetic variants of ovine and caprine milk were identified by CE.
      In order to carry out this identification, collected fractions from a cation
      exchange FPLC separation were injected by CE.

PMID- 9175275
TI  - Complete resolution of imidodipeptide mixtures in urine of prolidase-deficient
      patients using micellar electrokinetic chromatography.
AB  - The use of capillary zone electrophoresis as an efficient method for the
      identification of urinary imidodipeptides of prolidase-deficient patients has
      already been reported. However, owing to the complexity of the components
      excreted, the resolution of electrophoretic patterns obtained was poor. Here we
      examine the use of micellar electrokinetic chromatography to enhance peak
      resolution in order to obtain better insight into the electropherograms of
      patients' urine. The usefulness of sodium dodecyl sulphate as surfactant is
      reported: refined electropherograms were achieved using 35 mM sodium borate, pH
      8.3 containing 65 mM sodium dodecyl sulphate. Almost all peaks were baseline
      separated, collected and sequenced. This allowed us to define the exact
      imidodipeptide composition of patients' urine. The possibility of identifying and
      thus quantifying each single peak means that comparison of urinary imidodipeptide
      excretion patterns from different patients can be made and the hypothesis that
      peptide patterns can be correlated with differing clinical severity can be
      investigated.

PMID- 9175276
TI  - Direct monitoring of enzyme reactions using micellar electrokinetic capillary
      chromatography. Optimisation of drug glucuronide and sulfate conjugate
      hydrolysis.
AB  - This paper demonstrates the use of micellar electrokinetic capillary
      chromatography (MECC) to monitor enzyme reaction conditions. The hydrolysis
      reactions of model conjugated substrates (morphine and reduced flunixin
      glucuronides, napthyl sulfate), by proprietary beta-glucuronidase preparations,
      were studied under varied experimental conditions. Reactions were carried out in
      autosampler vials with incubation in a thermostatted CE autosampler tray. MECC
      was performed using borax buffer (17.5 mM, pH 9.3) modified with sodium dodecyl
      sulfate (70 mM). Repetitive injections were made from the sample vial throughout
      the course of the reactions at a frequency of up to 10 h-1. MECC provided a rapid
      and reproducible assay for the model substrates. Baseline interference from the
      enzymes prevented measurement of product increase, therefore substrate decrease
      was measured from the peak areas. Monitoring of reactions in this way has proved
      valuable in the optimisation of hydrolysis conditions used in sample preparation
      for drug analysis. beta-Glucuronidase preparations from Helix pomatia were found
      to give the best performance of those evaluated in terms of deconjugation
      efficiency.

PMID- 9175278
TI  - High-performance capillary electrophoresis of hyaluronic acid: determination of
      its amount and molecular mass.
AB  - The amount and the molecular mass of hyaluronic acid (HA) were determined by high
      performance capillary electrophoresis. HA was observed at around 15 min by using
      an untreated fused-silica capillary (75 microns I.D.) of 58 cm length (effective
      length, 50 cm) at 20 kV in 50 mM phosphate buffer (pH 4.0). Calibration curves
      showed good linearity from 0.01 mg/ml to 3.3 mg/ml for all HA samples examined.
      The lower limit of detection by monitoring the absorbance at 185 nm was 1.0
      microgram/ml at the signal-to-noise ratio of 5. HA samples were examined in a
      buffer containing pullulan (PU) as an additive for the matrix formation material.
      The HA samples showed marked peak-broadening when analyzed in the buffer solution
      containing PU with a specified molecular mass. The peak broadening was based on
      the dispersion of the molecular mass of the HA sample analyzed.

PMID- 9175277
TI  - Quantitation of acetaminophen and salicylic acid in plasma using capillary
      electrophoresis without sample pretreatment. Improvement of precision.
AB  - Capillary electrophoresis has become one of the most attractive techniques in the
      analysis of biological samples. Pharmaceuticals in human plasma can easily be
      determined on uncoated fused-silica capillaries without any sample pretreatment.
      Intra- and inter-day precision values of about 1-2% R.S.D. (n = 20) and 2-3%
      R.S.D. (n > 80) respectively are obtained using a sodium dodecyl sulfate
      containing borate buffer, pH 10 and acetonitrile as a between-run rinsing
      reagent. This method is highly robust, no breakdowns of the current or capillary
      blockings were observed for several weeks. The general applicability is
      demonstrated for several model drugs. The effectiveness of other rinsing
      procedures including enzyme-containing solutions, different organic solvents and
      hydrofluoric acid is discussed.

PMID- 9175279
TI  - Evaluation of phytic acid as a buffer additive for the separation of proteins in
      capillary electrophoresis.
AB  - The use of phytic acid to improve protein analysis by capillary electrophoresis
      (CE) is becoming more and more popular. Due to its size and number of negative
      charges (up to 12) it provides a high ionic strength combined with a low
      conductance resulting in an efficient decrease of wall adsorption for proteins.
      Because of its twelve acidic groups, phytic acid can be used as a buffer over a
      wide pH range (pH 2-11). The limited wall adsorption of proteins using phytic
      acid-containing buffers is observed for buffers with a pH of 5.5 and higher. With
      a monoprotic buffer, most of the investigated proteins show wall adsorption at
      the pH values studied. In case of a phytic acid buffer, wall adsorption is
      reduced by a factor of 2-4. The use of phytic acid both as a modifier and as a pH
      buffer results in more pronounced differences between the various protein
      mobilities compared with the use of monoprotic buffers. As a result this feature
      can be used to improve resolution in protein separations.

PMID- 9175280
TI  - Mercury speciation and accumulation in Bangladesh freshwater and anadromous fish.
AB  - Total mercury concentration in the muscle of 417 fish of 12 common freshwater and
      four anadromous species from Bangladesh were low, varying from 2 to 430 ng/g
      fresh wt. Depending on Hg speciation, three types of accumulation mechanisms were
      defined. Type I covers the majority of species and describes a pattern widely
      accepted as 'normal', with increasing levels of organic (methyl) mercury with
      length (age), combined to a low and constant inorganic level. This accumulation
      pattern leads to a relative increase of the organic mercury fraction with age,
      eventually reaching 90-100% of organic mercury in full grown specimens. Type II
      is found in both planktivorous genera only and showed increasing levels of
      inorganic mercury combined to low and constant organic mercury levels, leading to
      a relative decrease in organic mercury fraction with age. This unexpected pattern
      was only reported in cases of some marine species where it seemed to be linked to
      demethylation mechanisms or regional influences on Hg levels. A third
      intermediate accumulation pattern with increasing concentrations of both the
      organic and the inorganic Hg fraction with age was found in one bottom dwelling
      species only. The implications of these observations for the accumulation
      mechanisms of mercury in fish are discussed.

PMID- 9175282
TI  - Detection of heterogeneity of 18S rRNA inter-genes and mutation arising during
      PCR amplification.
AB  - Direct sequencing revealed sequence heterogeneity among ribosomal RNA gene (rDNA)
      operons, consisting of 8 base heterogeneous sites on the 18S rDNA of Galactomyces
      citri-aurantii IFO 10822, and 6 base heterogeneous sites in the same region on
      the 18S rDNA of G. citri-aurantii IFO 10821. Sequence analysis of the cloned 18S
      rRNA genes of 14 species (19 strains) of ascomycetous yeast-like fungi detected a
      total of 32 substitutions between two cloned sequences from each of 10 strains.
      Eight substitutions came from heterogeneity of G. citri-aurantii IFO 10822, and
      24 substitutions were predicted to be due to misincorporation by the Taq DNA
      polymerase. A low frequency of random substitution, estimated to occur in PCR at
      approximately 1 in 2690 nucleotides, was detected; and transitions occurred 7
      times more frequently than transversions.

PMID- 9175283
TI  - Maximal androgen blockade versus total androgen suppression.
AB  - As long as advanced prostate cancer remains androgen-dependent, it can be treated
      by castration in combination with anti-androgens. When despite maximal androgen
      blockade (MAB), progression occurs, the anti-androgen withdrawal can result in
      partial remission. Otherwise corticosteroids can be used in low doses in order to
      suppress the androgens originating from the adrenal gland: total androgen
      suppression (TAS). The minimal side effects and the low cost price of this
      treatment are important advantages, given the fact that only few efficient
      cytostatic agents are actually available for hormone-escaped prostate cancer.
      About 30% of the patients with advanced prostate cancer that became androgen
      independent will show a secondary remission under low doses hydrocortisone or
      prednisone.

PMID- 9175284
TI  - Contemporary non-imaging methods in diagnosis of bladder cancer: a review.
AB  - The early diagnosis of bladder cancer is central to the effective treatment of
      the disease. Presently, the detection of bladder tumors relies on cystoscopy and
      there are no methods available to easily and specifically identify the presence
      of bladder cancer cells. A variety of new technologies and potential tumor
      markers are being studied in bladder cancer and some are being translated into
      clinical use. It is important to realise that all available results on the
      diagnostic value of tumor markers do not allow firm clinical recommendations, but
      tests based on biomarkers will undoubtedly influence the management of bladder
      cancer in the near future.

PMID- 9175285
TI  - Diagnosis and treatment of psychosocial induced anejaculation or anorgasm by
      vibratory stimulation.
AB  - Electrovibration (100 Hertz, 6000 vibrations/min.) at the frenulum was used for
      diagnosis and treatment of idiopathic anejaculation and anorgasm in 7 men. In 3
      others it was used to obtain semen for medically assisted fertilisation. It was
      used also with a disabled young woman to obtain orgasm. Ejaculation and orgasm
      are rapidly obtained in most cases.

PMID- 9175286
TI  - Adenocarcinoma of the urachus: 3 case reports and a review of the literature.
AB  - Urachal carcinoma of the bladder is a very rare tumor which has to be
      differentiated from primary adenocarcinoma of the urinary bladder. The treatment
      of choice is extended partial cystectomy with inclusion of the umbilicus and the
      peritoneum. Symptoms occur late and the diagnosis has to be made by preoperative
      transurethral biopsy. We herein report on 3 cases of urachal adenocarcinoma of
      the urinary bladder and reviewed the literature.

PMID- 9175287
TI  - Dentistry in another EC country: Germany.
AB  - There are many similarities between dental education and treatment provision in
      the UK and Germany but also some important differences. V Hadden was interested
      to learn about the health care system in Germany, especially as the UK may soon
      follow European practice.

PMID- 9175288
TI  - New periodontal therapies.

PMID- 9175289
TI  - The future of dental amalgam: a review of the literature. Part 3: Mercury
      exposure from amalgam restorations in dental patients.
AB  - This is the third article in a series of seven on the future of dental amalgam
      and covers mercury exposure from functioning dental amalgam restorations in
      patients. It firstly discusses the evidence for mercury release from amalgam
      fillings by considering the mechanisms of mercury release and its measurement in
      the expired air and the intra-oral air. In this connection it also discusses the
      various factors involved in the accurate measurement and calculation of mercury
      levels in these situations. It finally describes the various attempts to
      calculate the daily mercury dose from dental amalgam fillings and considers the
      likely accuracy of these calculations.

PMID- 9175290
TI  - Prophylactic removal of impacted third molars: an assessment of published
      reviews.
AB  - OBJECTIVE: To evaluate published reviews of the appropriateness of prophylactic
      removal of impacted third molars. DESIGN: Systematic review and critical
      appraisal of relevant reviews. METHODS: Computerised databases (Medline and
      Embase), the Index to Dental Literature, and the references of articles were
      searched to identify relevant reviews. MAIN OUTCOME MEASURES: Pathologies
      associated with impacted third molars and outcomes following surgical removal of
      third molars. RESULTS: Twelve published reviews were assessed. Major
      methodological problems in these include that authors did not describe review
      methods such as literature search strategy and criteria for inclusion of primary
      studies. Reviews with similar aims included different sets of primary studies as
      evidence. Details of primary studies quoted were seldom sufficient for readers to
      judge the reliability of the evidence. With the exception of two reviews with
      poorer quality, the reviews concluded that there is a lack of evidence to support
      the prophylactic removal of impacted third molars. Two decision analyses also
      concluded that, on average, patients' long-term wellbeing is maximised if
      extraction is confined to those impacted third molars with pathology.
      CONCLUSIONS: In the absence of good evidence to support prophylactic removal,
      there appears to be little justification for the removal of pathology-free
      impacted third molars.

PMID- 9175291
TI  - Student drop-out from UK dental schools.
AB  - OBJECTIVE: To determine the level of student drop-out from UK dental schools and
      to establish if drop-out is increasing, remaining steady or decreasing. DESIGN:
      Retrospective analysis of data from the University Statistical Record. SETTING:
      UK dental schools 1989-1994. SUBJECTS AND METHODS: The data covered all dental
      students entering and leaving dental schools during the relevant time period.
      RESULTS: The drop-out rate from UK dental schools between 1989 and 1994 ranged
      from 8.4% to 16.8% and is equivalent to the output of two to three medium-sized
      dental schools. Drop-out rate was higher in the three most recent years studied
      (1992-1994; 14.8%) than in the three earliest years studied (1989-1991; 10.6%).
      CONCLUSIONS: Student drop-out is a significant and increasing problem for UK
      dental schools. Unless controlled, it will result in fewer dentists qualifying in
      the UK and exacerbate shortages in qualified dentists that may occur in future
      years.

PMID- 9175292
TI  - Lingual ulceration related to inhalers used for respiratory disease.
AB  - A chronic ulcer of the tongue is reported, resulting from the use of inhalers for
      respiratory disease. This complication was managed by the use of a spacer device.

PMID- 9175293
TI  - The role of the dental team in the promotion of smoking cessation.
AB  - Dentists and their support staff are in an ideal position to help patients cut
      down or stop smoking. In this paper Professor Palmer and Dr Newton review the
      literature on the promotion of smoking cessation in dental settings so that
      members of the dental team will feel more confident about helping and assisting
      patients to reduce their smoking habits.

PMID- 9175294
TI  - Letter from California: what is managed health care?
AB  - At a recent meeting I attended in Bournemouth there was a lot of talk about
      'managed care' in medicine and dentistry arriving in the UK. Managed care has
      already been introduced in the US and is the subject of many passionate debates.
      This article reviews managed care in the US and how it has affected health care
      over the last few years.

PMID- 9175295
TI  - Radiofrequency catheter ablation of slow pathway in 760 patients with
      atrioventricular nodal reentrant tachycardia--long-term results.
AB  - BACKGROUND: Although selective radiofrequency catheter ablation of the slow
      atrioventricular (AV) nodal pathway has provided a curative therapy for patients
      with AV nodal reentrant tachycardia, information about the long-term result of
      radiofrequency catheter ablation in patients with different types of AV nodal
      reentrant tachycardia was not available. This study was to investigate the long
      term effect of selective slow pathway ablation in a large group of consecutive
      patients with AV nodal reentrant tachycardia. METHODS: From December 1990 to June
      1996, 760 consecutive patients with clinically documented AV nodal reentrant
      tachycardia received radiofrequency catheter ablation of antegrade and/or
      retrograde slow AV nodal pathway at this electrophysiologic laboratory. The data
      of electrophysiologic characteristics and long-term follow-up were collected. The
      success rate, complication rate and recurrence rate were analyzed. RESULTS: There
      were 669 slow-fast form AV nodal reentrant tachycardia, 27 fast-slow form AV
      nodal reentrant tachycardia, 13 variant form AV nodal reentrant tachycardia, and
      51 multiple forms of AV nodal reentrant tachycardia. The electrophysiologic
      characteristics were different among these four groups. However, radiofrequency
      catheter ablation attained a 99% success rate in all the four groups with
      different types of tachycardia. There were 5 accidental injuries to AV
      conduction. Three of the 5 patients needed implantation of pacemakers. During the
      follow-up period, there were 14 (1.8%) recurrence of AV nodal reentrant
      tachycardia. All of the 14 patients had a successful second ablation without
      recurrence. CONCLUSIONS: This study demonstrated that radiofrequency catheter
      ablation of slow pathway was a highly effective treatment modality for patients
      with various types of AV nodal reentrant tachycardia. Furthermore, the incidence
      of complication rate and recurrence rate were low in an experienced center.

PMID- 9175296
TI  - Long-term results of radiofrequency catheter ablation in patients with Wolff
      Parkinson-White syndrome.
AB  - BACKGROUND: Information about the long-term results of radiofrequency catheter
      ablation, electrophysiologic characteristics of differently located accessory
      pathways, and the difference between a single accessory pathway and multiple
      accessory pathways was limited. METHODS: Nine hundred and thirty-one patients
      with 1016 accessory pathways (APs) received electrophysiologic study and
      radiofrequency catheter ablation between July 1, 1989 and June 31, 1996. Group 1
      included 856 (91.9%) patients with a single AP and Group 2 included 75 (8.1%)
      patients with multiple APs. The follow-up period was 48 +/- 37 months (range, 2
      to 84 months). RESULTS: Nine hundred and thirteen patients (98.1%) had successful
      ablation with a complication rate of 1.5%. In Group 1, left free wall pathways
      were ablated with fewer radiofrequency pulses, shorter procedure time, shorter
      radiation exposure time and a lower recurrence rate than those at other
      locations. Comparisons between Group 1 and Group 2 showed that the latter had
      higher incidences of antidromic tachycardia (3% vs 13%, p < 0.05) and atrial
      flutter/fibrillation (26% vs 37%, p < 0.05). Regarding radiofrequency catheter
      ablation, Group 2 needed more radiofrequency pulses (8.7 +/- 7.8 vs 5.5 +/- 7.7,
      p < 0.001), longer procedure time (3.3 +/- 1.4 vs 2.1 +/- 1.0 hours, p < 0.05)
      and radiation time (49 +/- 27 vs 29 +/- 19 minutes, p < 0.001), and a higher
      recurrence rate (10.6% vs 3.3%, p < 0.005) than those in Group 1. Thirty-six
      patients (4%) with recurrence had more right-side pathways than those without
      recurrence. In addition, difficult ablation (longer procedure time, longer
      radiation time and more radiofrequency pulses) was associated with a higher
      recurrence rate. CONCLUSIONS: These findings demonstrated that a high success
      rate with a low recurrence and low complication rate of radiofrequency catheter
      ablation could be achieved in a large population with APs during a long follow-up
      period.

PMID- 9175297
TI  - The outcome of terminal liver cirrhosis patients requiring mechanical
      ventilation.
AB  - BACKGROUND: Liver cirrhosis is a common problem in Taiwan. Without liver
      transplantation, patients with end-stage liver cirrhosis frequently die of
      various complications and often require mechanical ventilatory support prior to
      their death. The purpose of this study was to investigate the in-hospital and
      short-term outcome of such patients. METHODS: A retrospective review of 47
      medical records of mechanically ventilated patients with primary diagnosis of
      liver cirrhosis, admitted from November 1990 to September 1993, allowed analysis
      of disease course and outcome for these patients. RESULTS: Among the 47 patients,
      a Child-Pugh's class A patient receiving temporary mechanical ventilation (MV)
      after elective devascularization surgery was excluded from analysis. Among the
      remaining medically treated 46 patients, there were 33 Child-Pugh's class C
      patients, 9 class B patients and 4 unclassified patients. Primary reasons for
      endotracheal intubation and MV included airway protection, acute respiratory
      distress and shock. Of these patients, shock was present in 39 cases, upper
      gastrointestinal bleeding in 34, systemic inflammatory response syndrome in 32,
      renal insufficiency with creatinine greater than 1.3 mg/dl in 32, bacteremia in
      14, parenchymal lung disease in 16, spontaneous bacterial peritonitis in 10, and
      intracerebral hemorrhage in 1 during their hospital courses. Thirty-eight
      patients (83%) died within 72 hours after being placed on mechanical ventilation.
      Patients requiring MV with complications of bacteremia, parenchymal lung disease
      or renal insufficiency during hospitalization were found to have a 100% mortality
      rate. Successful weaning occurred in only 3 of 46 patients (8.7%). Of these
      three, two (4.3%) went home alive and had survived over six months after
      discharge. CONCLUSIONS: It was concluded that cirrhotic patients requiring MV
      have an extremely poor prognosis. Patients and their families should be fully
      informed of the prognosis, and routine use of MV should not be encouraged in
      patients with terminal stage liver disease.

PMID- 9175298
TI  - The route of seminal vesicle involvement in adenocarcinoma of prostate:
      lymphaticovascular or local extension?
AB  - BACKGROUND: Adenocarcinoma of the prostate with seminal vesicle involvement
      indicates a rather poor prognosis. The aim of this study is to evaluate the route
      of seminal vesicle involvement via lymphaticovascular or local extension, as a
      possible way which may determine the extent of disease as systemic or local.
      METHODS: In a retrospective study of 32 patients who underwent radical
      prostatectomy for localized cancer of the prostate, medical records and imaging
      studies were reviewed, and the histopathological slides of the resected specimens
      were rechecked. RESULTS: Of 32 patients, 12 (37.5%) had seminal vesicle
      involvement. Seven patients had involvement of bilateral seminal vesicles and
      five had unilateral involvement. Tumor cells invaded the muscle portion of
      seminal vesicle from the adjacent prostatic tissues in all 12 patients. Four of
      the seven patients with involvement of bilateral seminal vesicles developed bony
      metastasis 7 to 12 months after operation. No patient with unilateral involvement
      of seminal vesicle was found to have disease progression to bony metastasis
      during follow-up for as long as 39 months. CONCLUSIONS: The route of seminal
      vesicle involvement in prostate cancer was through local extension in all of our
      patients. Involvement of bilateral seminal vesicles may have more chances to
      develop bony metastasis than unilateral involvement. Further study with a large
      number of patients is necessary to clarify the issue regarding the route of
      seminal vesicle involvement in adenocarcinoma of prostate.

PMID- 9175299
TI  - The double-blind test of sodium hyaluronate (ARTZ) on osteoarthritis knee.
AB  - BACKGROUND: At this time, no definite treatment exists for osteoarthritis
      disease. Hyaluronate (ARTZ) is one of the most important components of synovial
      fluid. It is generally accepted that hyaluronic acid protects the articular
      cartilage and soft tissue surfaces from trauma during joint function. METHODS:
      Ninety patients with 116 knees diagnosed as early arthritis (mild to moderate) by
      four senior orthopaedic surgeons were selected to join this study. The trial
      design was applied with a double-blind model. The selected patients were randomly
      injected with 2.5 ml drugs (ARTZ or placebo) intra-articularly once a week for
      five consecutive weeks without the use of local anesthetic drugs. Evaluation
      results included grading of subjective and objective symptoms and daily
      activities. The follow-up period was up to six months after initial injection.
      RESULTS: According to the results of clinical evaluation and statistical
      analysis, SPH (ARTZ) is quite effective for osteoarthritis knees, and
      significantly better than the placebo. The effective peak was one week after five
      injections of ARTZ. The effective period could last up to three months without
      additional treatment. The efficacy of ARTZ on osteoarthritis knees was more
      prominent for relief of motion pain and improvement of knee movement. No side
      effects developed during a six month period. CONCLUSIONS: Based on clinical
      results here, SPH is a safe drug for administration as an alternative approach to
      treat the osteoarthritis knee.

PMID- 9175300
TI  - Aortic stenosis in children: 19-year experience.
AB  - BACKGROUND: In the Taiwanese literature, few articles describe the pertinent
      features of aortic stenosis (AS). This study explores the features of AS in
      Chinese children. METHODS: 3808 children with congenital heart diseases have
      undergone cardiac catheterization at our institution over the past 19 years.
      Among them, 51 (1.3%) cases were AS. The clinical, electrocardiographic,
      echocardiographic and catheterization findings, the methods of treatment and
      outcomes were reviewed. RESULTS: Valvular AS occurred in 39 children (76.5%),
      subvalvular AS in 5 (9.8%), and supravalvular AS in 7(13.7%). Male was
      predominant (M/F ratio, 2.6) except in supravalvular type. Forty-three patients
      had associated cardiovascular defects. Aortic regurgitation (AR) was the most
      common one. Most patients (56.9%) were asymptomatic. Classic symptoms included
      exertional dyspnea (17.6%), syncope (9.8%), and chest pain (7.8%), etc. Left
      ventricular hypertrophy was noted in 31.2% of cases. The mean duration of follow
      up was 3.9 +/- 3.4 years. Ten patients received open-heart surgery and 2 received
      balloon dilation. The pressure gradients across the stenotic area dropped from
      95.3 +/- 29.3 to 51.4 +/- 35.8 and 53.1 +/- 12.3 mm Hg in early and late Doppler
      follow-up studies, respectively (p < 0.05). The average gradient increased from
      36.9 +/- 25.3 to 40.8 +/- 32.6 mm Hg in nonsurgical patients. The result was
      insignificant. No mortality occurred following open-heart surgery. One child
      expired due to heart failure after the ligation of the patent ductus arteriosus
      and dilation of the stenotic aortic valve on the surgical table under general
      anesthesia. Autopsy revealed valvular rupture. In the nonsurgical group, no
      mortality occurred, but one patient was brought home by parents in critical
      condition and later died. CONCLUSIONS: We found that some clinical features of AS
      in Chinese children were different from those in occidental populations. (1) The
      incidence of AS was relatively low. (2) Subvalvular AS was the least common type
      in contrast to supravalvular AS in western studies. (3) Male predominance was not
      present in the supravalvular type, which lacked sexual proclivity. (4) Williams
      syndrome was a more frequently associated anomaly. Turner syndrome was not
      present in our study. (5) Isolated AS was less frequent. (6) The unusual finding
      such as right ventricular hypertrophy on EKG was present due to associated
      cardiac anomalies. Open-heart surgery is effective and safe, but the efficacy of
      balloon dilation requires further investigation.

PMID- 9175301
TI  - Primary aldosteronism due to unilateral adrenal hyperplasia: a case report.
AB  - Primary aldosteronism is one of the differential diagnosis of secondary
      hypertension. This is usually caused by an aldosterone producing adenoma or
      bilateral adrenal hyperplasia which comprise about 65% and 30% of the cases,
      respectively. However, less than 1% of primary aldosteronism is caused by
      unilateral adrenal hyperplasia which is a relatively rare subset of primary
      aldosteronism. The clinical and biochemical manifestations of the disorder are
      indistinguishable from aldosterone-producing tumor, and a definitive diagnosis
      can only be made by pathological finding. A 33-year-old male Chinese patient
      presented with hypertension, hypokalemia, metabolic alkalosis, and the
      hypersecretion of aldosterone associated with suppressed plasma renin activity
      which is a typical hallmark of primary aldosteronism. Image studies including
      both magnetic resonance imaging (MRI) and 131I NIP-59 scan as well as postural
      test suggested an aldosterone-producing tumor of the right adrenal gland.
      Unilateral adrenectomy and pathological examination of the right adrenal gland
      eventually proved a case of unilateral adrenal hyperplasia. Blood pressure,
      plasma potassium, aldosterone and renin activity levels returned to normal two
      weeks after operation and had remained normal at up to one year of follow up. In
      addition, a saline loading test showed normal suppression of plasma aldosterone
      level one year after the operation, suggesting that the function of the left
      adrenal gland remains normal. The etiology of unilateral adrenal hyperplasia is
      unclear and the future recurrence of the disease is possible. Long-term follow-up
      is necessary to ensure the cure of this disorder.

PMID- 9175302
TI  - Spontaneous remission in acute myelogenous leukemia: a case report.
AB  - A 62-year-old woman with hypocellular acute myelogenous leukemia experienced
      spontaneous remission after repeated episodes of severe infections. Transient
      surge of profuse blasts in the peripheral blood was observed prior to the
      occurrence of spontaneous remission. The duration of the spontaneous remission
      was relatively short, and the disease relapsed five months later. A second
      complete remission was achieved after chemotherapy with low-dose cytosine
      arabinoside. The patient finally died of relapsed leukemia after a second
      remission of three year duration. Possible mechanisms implicated in the
      occurrence of spontaneous remission in this patient are discussed.

PMID- 9175303
TI  - Orthoclone OKT3 for graft failure after allogeneic bone marrow transplantation: a
      case report.
AB  - Orthoclone OKT3 has been used in the prophylaxis or treatment of acute graft
      versus-host disease (GVHD). No previous report of Orthoclone OKT3 in the
      treatment of marrow allograft failure has been found. Here a case of chronic
      myelocytic leukemia is presented where the patient received unrelated bone marrow
      transplantation and developed late graft failure. After failing all other
      immunosuppressive agents, marrow allograft was successfully rescued by the use of
      Orthoclone OKT3.

PMID- 9175304
TI  - Application of rearrangements of T cell receptor gene in the diagnosis of
      mediastinal T-lymphoblastic lymphoma: a case report.
AB  - The cytologic diagnosis of lymphoid cells in pleural effusion is not readily
      apparent. The atypical lymphocytes in reactive process or viral infection may
      mimic immature lymphoblasts in lymphoblastic lymphoma. Therefore, an objective
      and reliable method to identify malignant lymphoid cells is important. Here we
      reported the application of T cell receptor (TCR) gene analysis, together with
      cytomorphology and immunophenotypic studies, to establish the diagnosis of T
      lymphoblastic lymphoma in a 20-year-old female who presented with a mediastinal
      tumor and pleural effusion. The diagnosis of malignant lymphoma was suspected by
      cytology and then confirmed by TCR beta chain (TCR beta) gene rearrangement. The
      rearrangement of TCR beta gene revealed by Southern blot technique implied a T
      monoclonal lymphoid population which is most likely malignant. Immunophenotypic
      studies revealed expression of TdT and T cell antigens indicating a T
      lymphoblastic lymphoma. As shown in this case, antigen receptor gene analysis can
      be conducted with a much smaller number of cells to identify a malignant clone
      among a heterogeneous cell population.

PMID- 9175305
TI  - Leiomyosarcoma of the left atrium: a case report.
AB  - Primary malignant cardiac tumors are uncommon, and cardiac leiomyosarcoma is
      extremely rare. We reported a case of left atrial (LA) leiomyosarcoma with
      unusual clinical manifestations. A 28-year-old female presented with unknown
      cause of fever, body weight loss and anemia for two months. Echocardiography and
      magnetic resonance image study disclosed a 5 x 3 x 3.6 cm3 lobulated mass in the
      LA with invasion to its posterior wall. Histologic and immuno-histochemical
      studies of the resected specimen revealed a picture of leiomyosarcoma. The
      patient improved after surgical resection and post-operative chemotherapy. The
      literature was reviewed with a discussion of the clinical manifestations,
      diagnosis and treatment strategy of this rare tumor. Diagnosis of LA
      leiomyosarcoma is frequently delayed to make a very poor prognosis. Postoperative
      chemotherapy should be considered because of highly possible incomplete
      resection. However, an optimal treatment regimen remains unknown.

PMID- 9175306
TI  - Chylothorax as a complication of anterior thoracic interbody fusion: a case
      report.
AB  - A case is reported of chylothorax following an uneventful anterior thoracic
      interbody spinal fusion. To present knowledge, this complication is reported to
      occur in 0.2% of intrathoracic operations, and may give rise to 50% mortality
      unless stress properly recognized and managed.

PMID- 9175307
TI  - Adverse events after school leavers received combined tetanus and low dose
      diphtheria vaccine.
AB  - Since October 1994, children in the United Kingdom have been offered tetanus
      vaccine combined with a low dose of diphtheria vaccine (Td) at the age of 15 to
      18 years. It is recommended that schoolchildren who have already received a
      booster of tetanus vaccine at the time of an injury should be given low dose
      diphtheria vaccine alone. When this vaccine is not available, however, it is
      recommended that Td vaccine should be given to all children. This study was
      performed to compare the frequency of adverse events after Td vaccine in 15 year
      old children with and without a history of an additional tetanus booster in the
      preceding 10 years. Two hundred and sixty-five children were followed up-52
      pupils (20%) with a history of an additional tetanus booster, 157 (59%) with no
      such history, and 56 (21%) whose history was unclear. Mild local reactions were
      common and occurred more commonly in children with a history of an additional
      tetanus booster. Twenty-three pupils (44%) who had received an additional tetanus
      booster had swelling over 2 cm diameter at the injection site, compared with only
      39 (25%) of those with no such history (p < 0.013). Systemic symptoms were
      equally unusual in both groups. Only three children experienced symptoms
      attributed to vaccine that were severe enough for them to miss school or attend a
      doctor; and none of these had received an additional tetanus booster. We conclude
      that, in the absence of a supply of low dose diphtheria vaccine, offering Td
      vaccine to children with a history of additional tetanus booster is an acceptable
      policy.

PMID- 9175308
TI  - Management of school leavers given a diphtheria and tetanus vaccine intended for
      children instead of the intended low dose preparation.
AB  - In November 1995, 102 school leavers in two North Staffordshire schools were
      given high dose diphtheria and tetanus vaccine (intended for primary immunisation
      of children) rather than a preparation with a low dose of diphtheria vaccine
      intended for adults and adolescents. We describe the management of the incident
      and the action taken to minimise the risk of such an error being made again.
      Pupils who had received the high dose vaccine and a control group were surveyed
      with a self-administered questionnaire. Thirteen children out of 67 given the
      higher dose diphtheria vaccine consulted their general practitioner and the same
      number had time off school, compared with none of 25 from a control school. This
      excess morbidity was probably attributable to the higher dose of diphtheria
      vaccine.

PMID- 9175309
TI  - Outbreak of trichinosis in France associated with eating horse meat.
AB  - The investigation of a trichinosis outbreak in Auvergne, France identified 23
      cases in 12 households living in two cities-Clermont-Ferrand and Montlucon
      between 15 February and 7 March 1991. One patient required intensive care, 15 had
      major symptoms, and seven had minor or no symptoms. Two case control studies
      demonstrated a significant (p < 0.01) association between eating horse meat and
      acute trichinosis. Veterinary services found that three supermarkets where the
      patients had bought horse meat during the suspected period had been supplied by a
      single wholesaler. The analysis of the wholesaler's records revealed that the
      implicated horse meat had been imported from a slaughterhouse in the United
      States. This outbreak occurred despite a requirement in France for all meat from
      horses slaughtered in France and in countries exporting meat to France to be
      examined systematically for trichinella.

PMID- 9175310
TI  - An outbreak of Salmonella enteritidis phage type 4 infection in a rural community
      in Northern Ireland.
AB  - An outbreak of gastroenteritis arose in people who attended a charity barbecue at
      a hotel in a rural area of Northern Ireland in July 1995. About 120 people
      attended the barbecue, 98 of whom were identified. Fifty-one of them and seven
      members of hotel staff met the case definition. An epidemiological investigation
      showed that illness was significantly associated with eating foods containing
      mayonnaise that had been prepared using raw shell eggs and stored at too high a
      temperature. Salmonella enteritidis phage type 4 was cultured from 17 out of 24
      faecal specimens received from people who attended the barbecue and in 17 out of
      34 faecal specimens from staff, including all seven staff cases. The primary
      source of infection was not identified despite thorough investigation. This paper
      highlights the value of administering questionnaires by telephone when
      investigating community outbreaks of infection in rural areas, the important role
      of general practitioners in the identification of community outbreaks, and the
      need to periodically reiterate public health messages, in particular for food
      handlers and caterers.

PMID- 9175311
TI  - Preliminary results from the PHLS case control study of Vero cytotoxin producing
      Escherichia coli O157 infection in England.

PMID- 9175312
TI  - Mild hyperhomocysteinemia and arterial occlusive disease.

PMID- 9175313
TI  - Early hemopoietic progenitors in the peripheral blood of patients with severe
      aplastic anemia (SAA) after treatment with antilymphocyte globulin (ALG),
      cyclosporin-A and G-CSF.
AB  - BACKGROUND AND OBJECTIVE: We previously reported that patients with acquired
      severe aplastic anemia (SAA) treated with antilymphocyte globulin (ALG), 6
      methylprednisolone, cyclosporin A (CyA) and granulocyte colony-stimulating factor
      (G-CSF) can mobilize peripheral blood hemopoietic progenitors (PBHP). The aim of
      the present study was to assess phenotypic and functional properties of these
      PBHP. METHODS: We studied seven patients who underwent 43 leukophereses (median
      5) between day +30 and +80 following ALG, while in treatment with CyA and G-CSF.
      Mobilized peripheral blood hemopoietic progenitors were analyzed using surface
      markers, conventional assays for clonogenic cells (CFU-GM, BFU-E, CFU-GEMM) as
      well as the recently developed assay for long-term culture initiating cells (LTC
      ICs). RESULTS: The proportion of CD34+ cells ranged between 0% and 5.4% (median
      0.3%), CD34+DR between 0% and 3.5% (median 0.1%) and CD8+ cells between 3.3% and
      56% (median 31%). When light density mononuclear cells (MNC) were plated in
      vitro, we could grow colony-forming units-granulo-macrophage (CFU-GM) (range 0
      45/10(5) MNC; normal controls 21-200/10(5) MNC), burst-forming units-erythroid
      (BFU-E) (range 0-5/10(5) MNC; normal controls 0-6/10(5) MNC), multipotent
      colonies (CFU-GEMM) (range 0-3/10(5) MNC; normal controls 0-6/10(5) MNC) and high
      proliferative potential colony-forming cells (HPP-CFC) (range 0-3.4/10(5) MNC).
      We studied long-term culture-initiating cells (LTC-ICs) in 18 leukophereses from
      4 patients; in 7/18 samples LTC-ICs were grown at low frequency (range 0.4
      2/10(6) MNC) (normal controls 5-130/10(6) MNC), and in one patient in the absence
      of CFU-GM growth. The total yield of LTC-ICs in two patients was 7.64 and 10.5 x
      10(2)/kg of body weight. INTERPRETATION AND CONCLUSIONS: This study suggests that
      cells with the phenotype and in vitro function of early hemopoietic progenitors
      are found, though in small numbers, in the peripheral blood of patients with SAA
      after treatment with immunosuppressants and prolonged G-CSF administration.
      Whether G-CSF-mobilized progenitors contribute to hemopoietic recovery in these
      patients remains to be determined.

PMID- 9175314
TI  - A contribution to the incidence of nucleoli in normal human blood monocytes.
AB  - BACKGROUND AND OBJECTIVE: Normal blood monocytes were studied in blood donors to
      provide more information on the presence of nucleoli and nucleolar types in these
      cells. METHODS: Nucleoli in monocytes were visualized using cytochemical
      procedures that detect RNA and characteristic nucleolar proteins, i.e.
      nucleophosmin, nucleolin, fibrillarin and AgNOR proteins, in peripheral blood
      smears. RESULTS: Nucleoli were detected in all blood monocytes. The nucleolar
      coefficient (number of nucleoli per cell) was 2.6 and no differences were found
      between men and women. Concerning the incidence of nucleolar types, monocytes
      from both male and female blood donors possessed mainly only inactive
      micronucleoli characteristic of mature or advanced maturation stages of blood
      cells; however, 16-20% of monocytes also contained functionally dominant ring
      shaped nucleoli, which reflect a reversible decrease of rRNA transcription and in
      blood cells are intermediate stages between actively transcribing large nucleoli
      in highly immature cells and inactive micronucleoli in terminal nucleolated
      maturation stages. Monocytes containing large nucleoli with a relatively uniform
      distribution of RNA characteristic of immature or stimulated blood cells were
      rare (< 2%). INTERPRETATION AND CONCLUSIONS: Nucleoli are present in all normal
      blood monocytes. The incidence of the main nucleolar types represents a very
      convenient complementary marker for evaluating the maturation and possibly the
      stimulated state of these cells.

PMID- 9175315
TI  - Effect of fludarabine and arabinosylcytosine on multidrug resistant cells.
AB  - BACKGROUND AND OBJECTIVE: Anthracyclines are first-line drugs in the treatment of
      acute leukemia, but the sensitivity of leukemic cells to anthracyclines can be
      downmodulated by multidrug resistance (MDR) transport proteins like Pgp. Pgp
      overexpression is negatively related to treatment response. Alternative drugs may
      be required to overcome the MDR problem. METHODS: Arabinosylcytosine (ara-C) and
      9-beta-D-arabinofuranosyl-2-fluoro-adenine monophosphate (fludarabine, F-ara)
      were tested alone and in combination in four pairs of leukemia and tumor non-MDR
      and MDR cell lines. Toxicity was assayed by growth inhibition with the
      microcultured MTT assay. RESULTS: MDR cells were more sensitive than or as
      sensitive as non-MDR cells to ara-C and to F-ara alone. The resistance index to
      ara-C was decreased upon pre-exposure of the MDR cells to low-dose F-ara (10
      ng/mL), showing that the combination of ara-C and F-ara was more active on MDR
      cells than on non-MDR parental ones. INTERPRETATION AND CONCLUSIONS: Neither
      sensitivity to ara-C nor sensitivity to F-ara was influenced by Pgp
      overexpression. These data provide a rationale for more extensive and more
      intensive testing of combinations of ara-C and F-ara in Pgp-mediated MDR acute
      leukemia. In relapsed/resistant and in secondary acute leukemias, increasing the
      dose of ara-C and combining ara-C with F-ara might be more rewarding than
      administering anthracyclines or other Pgp-processable compounds.

PMID- 9175316
TI  - Clinico-prognostic implications of increased levels of soluble CD54 in the serum
      of B-cell chronic lymphocytic leukemia patients. Results of a multivariate
      survival analysis.
AB  - BACKGROUND AND OBJECTIVE: Although less specific than sCD23, sCD54 levels have
      clinico-prognostic relevance in B-cell chronic lymphocytic leukemia (CLL). Since
      serological markers are now emerging as potentially important in CLL, we tried to
      verify whether sCD54 might complement clinical stages. METHODS: Serum levels of
      sCD54 were determined at the time of diagnosis in 115 previously untreated CLL
      patients. Results were correlated with clinicobiological parameters as well as
      with survival. RESULTS: Life-expectancy was significantly shorter in patients
      with higher serum levels of sCD54 (p < 0.001); however, in a Cox's multivariate
      survival analysis, the only variables which entered the regression model at a
      significant level were bone marrow (BM) histology (p = 0.03) and lymphocyte
      doubling time (LDT) (p = 0.04). Interestingly, when LDT was excluded from
      analysis the only significant variables were clinical stages (p < 0.05) and sCD54
      (p < 0.05). These results suggest that sCD54 and LDT give similar prognostic
      information. INTERPRETATION AND CONCLUSIONS: In CLL, sCD54 is a reliable
      prognostic parameter whose value is independent of clinical stages. When
      investigated in relation to clinical outcome, serum levels of sCD54 were able to
      predict progression to a more advanced clinical stage. On the basis of these
      data, an integrated clinico-biological classification which separates
      intermediate risk into two prognostic subgroups is proposed.

PMID- 9175317
TI  - Hairy-cell leukemia and alpha-interferon treatment: long-term responders.
AB  - BACKGROUND AND OBJECTIVE: In the 1980s alpha-interferon (alpha-IFN) dramatically
      improved the management of hairy cell leukemia (HCL), producing normalization of
      hematologic parameters including the disappearance of circulating hairy cells in
      the majority of treated patients, within 6 months. The quality and durability of
      the response depended on the duration of alpha-IFN treatment; progression of the
      disease consistently followed discontinuation of alpha-IFN. In this report, we
      examine the characteristics of long-term responders from our series of 44 HCL
      patients treated with alpha-IFN. METHODS: We report follow-up data on 44 HCL
      patients who underwent alpha-IFN as first-line treatment between 1985 and 1990.
      The alpha-IFN dose was 3 x 10(6) U daily for 12-15 months, with 20 patients
      continuing to receive the same dose three times a week as maintenance treatment
      for an additional 6-12 months. Of the 44 patients, 8 achieved a CR, 28 a PR and 8
      a MR, with an overall response rate of 82%. Thirty-eight (86%) of these patients
      showed disease progression and were retreated with alpha-IFN (2 pts), 2
      chlorodeoxyadenosine (35 pts), or pentostatin (1 pt). So far, all 38 patients are
      alive and in good unmaintained second response, except for two patients who
      developed a second neoplasm. RESULTS: Six of the 8 first complete responders are
      alive and have not required further treatment after completing alpha-IFN. These
      long responders most often (5/6) presented a hairy cell index (HCI) < 0.50 at
      diagnosis; all 6 registered a significant reduction in bone marrow infiltration
      (HCI < 0.10) after induction therapy and underwent alpha-IFN maintenance
      treatment. These three parameters turned out to be statistically significant when
      the long-term responders were compared with the failure patients subset (p =
      0.003 for HCI at diagnosis; p = 0.001 for HCI at the end of the induction phase;
      p = 0.003 for the maintenance phase). The median progression-free survival of
      these 6 long-term responders was 75 months (range, 62 to 78). INTERPRETATION AND
      CONCLUSIONS: Overall, alpha-IFN represents an excellent palliative treatment for
      most HCL patients. A small subset of these patients could become long-term
      responders following first-line alpha-IFN therapy alone.

PMID- 9175318
TI  - Early detection of bone marrow engraftment by amplification of hypervariable DNA
      regions.
AB  - BACKGROUND AND OBJECTIVE: After allogeneic bone marrow transplantation (BMT) it
      is important to be able to distinguish between the host and donor origin of cells
      in order to monitor the engraftment process. However, identifying whether the
      hematopoietic stem cells are of donor or recipient origin may be a difficult
      task. DNA studies using Southern blotting techniques or the amplification by PCR
      of regions in the human genome with high polymorphic neutral sequence variation
      showing Mendelian inheritance as variable number of tandem repeats (VNTR) can
      detect the origin of host bone marrow after BMT. We have tried to apply these
      sensitive systems of detection to the early stages of BMT when small numbers of
      regenerated cells are available for analysis. METHODS: We used in vitro
      polymerase chain reaction (PCR) amplification of three single-locus simple
      repetitive DNA sequences, all of which vary extensively in their repeat number
      among different individuals (VNTR D1S80, ApoB, and D17S5), to evaluate post
      transplant engraftment in six patients who showed no signs of peripheral blood
      engraftment at 2-3 weeks after transplant. We tested 2 patients with chronic
      myelogenous leukemia (CML), 2 with B-acute lymphoblastic leukemia (B-ALL), 1 with
      T-acute lymphoblastic leukemia (T-ALL), and 1 with aplastic anemia (SAA), all in
      prolonged aplasia following allogeneic bone marrow transplantation (BMT).
      RESULTS: In a sequential analysis protocol with the different loci, the donor was
      distinguishable from the recipient in all pairs with at least one of the three
      markers used. After 16 days (median 16.2; range 15 to 20 days) we found that
      complete chimerism was present in 5 patients: 4 of donor origin (= engraftment)
      and one of host origin (= rejection), this last case being one of mixed
      chimerism. In the 2 cases in which the presence (one complete and one partial) of
      host DNA was detected, rejection of the donor bone marrow followed, and in 1
      patient a second BMT was necessary. The other 4 patients with complete chimerism
      of donor origin achieved hematological reconstitution and we documented complete
      engraftment of donor bone marrow a few months later. INTERPRETATION AND
      CONCLUSIONS: Utilizing PCR to document early post-transplant engraftment and
      chimerism in the first month after BMT has the advantage over Southern blotting
      of being more sensitive and requiring small amounts of sample. It may also be
      useful for guiding subsequent therapeutic decisions.

PMID- 9175319
TI  - Detection of clonality by heteroduplex analysis of amplified junctional region of
      T-cell receptor gamma in patients with T-cell acute lymphoblastic leukemias.
AB  - BACKGROUND AND OBJECTIVE: Traditional gel electrophoresis of PCR amplification
      products of regions from T-cell receptor genes often does not differentiate
      monoclonal from polyclonal rearrangements. We used polymerase chain reaction
      (PCR) and heteroduplex analysis on polyacrylamide gels to improve the detection
      of monoclonal rearrangements. METHODS: We investigated heteroduplex analysis of
      the amplified V gamma-J gamma junctions of the rearranged T-cell receptor gamma
      (TcR-gamma) gene by electrophoretic separation on non-denaturing polyacrylamide
      gel (PAGE) in 8 T-cell acute lymphoblastic leukemia (T-ALL) patients analyzed at
      diagnosis. RESULTS: Clonal homoduplex and heteroduplex bands were present only in
      the T-ALL samples and not in controls. We confirmed clonality by direct
      sequencing of the V gamma-J gamma junction. In 2 instances the analysis was
      performed on samples obtained from the same patient at diagnosis and at relapse,
      respectively; the presence of the same clonal TcR-gamma rearranged cell remained
      detectable during clinical progression of the disease. INTERPRETATION AND
      CONCLUSIONS: Our heteroduplex analysis showed that separation of the PCR product
      by electrophoresis on non-denaturing PAGE is a rapid and convenient method for
      the detection of clonal TcR-gamma rearrangements in T-ALL.

PMID- 9175320
TI  - Estimation of bone marrow cellularity by means of vertebral magnetic resonance.
AB  - BACKGROUND AND OBJECTIVE: A magnetic resonance (MR) signal shows an inverse
      correlation with bone marrow cellularity. In this study, we investigated the
      possibility of estimating the degree of bone marrow cellularity by means of this
      non-invasive technique. METHODS: In 25 patients with different hematological
      disorders and homogeneous bone marrow distribution, the percentage of bone marrow
      cellularity was compared to the MR signal of four middorsal vertebrae in T1
      sequence. As internal control, the MR signal of the mid-dorsal spinal cord region
      was used. The results were expressed as the MR signal ratio (great mean MR signal
      of four vertebrae/MR signal of the spinal cord). RESULTS: The correlation
      coefficient (r) between both parameters was -0.93 (p < 0.0001). All observed
      values fell within the 90% limits of predicted values. The mean difference
      between observed and predicted bone marrow cellularity was 5.6 (SD 4.0)%.
      INTERPRETATION AND CONCLUSIONS: The measurement of the MR signal is not easy to
      standardize since it depends to a large degree on the control employed. The
      spinal cord proved to be a satisfactory internal control of the MR signal. Within
      defined conditions, MR can be useful for a rough estimate of bone marrow
      cellularity in several clinical situations, such as analysis of tumor burden for
      prognosis of some leukemias and the evaluation of response to therapy in both
      proliferative and hypoplastic disorders.

PMID- 9175321
TI  - Retrospective analysis of 23 cases with peripheral T-cell lymphoma, unspecified:
      clinical characteristics and outcome.
AB  - BACKGROUND AND OBJECTIVE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous
      group of post-thymic malignancies relatively uncommon in the Western world and
      their prognosis and therapeutic approach are still not well defined. The aim of
      this study was to retrospectively analyze the clinical, hematological and
      histological features at diagnosis, the relevance of the International Prognostic
      Index and the outcome of a group of 23 patients affected by peripheral T-cell
      lymphoma, unspecified (PTCL-U), according to the Revised European-American
      Classification of Lymphoid Neoplasms (REAL), observed between September 1985 and
      April 1995 at our Institution. METHODS: Patients were separated into different
      prognostic groups according to Ann Arbor stage, cell size and International
      Prognostic Index. All patients had been treated with multiagent combination
      chemotherapy, mainly CHOP (9 cases) and F-MACHOP (9 cases), and were evaluable
      for response. The treatment was intensified with allogeneic bone marrow
      transplantation (BMT) in 1 patient and with autologous BMT in 4 patients.
      RESULTS: Median age was 55 (range 18-77) years and 70% of the patients were
      males. Four patients were in stage II (17%), 5 in stage III (22%) and 14 in stage
      IV (61%). Patient risk was classified according to the International Prognostic
      Index as follows: 8 cases (35%) low risk, 2 cases (9%) low-intermediate, 8 cases
      (35%) high-intermediate, 5 cases (21%) high. Median follow-up time was 20 months
      (range 2-132). Median progression-free survival (PFS) and overall survival (OS)
      for all the patients studied were 10 and 34 months, respectively. Stage IV was
      associated with a poorer response rate and a shorter PFS (median 6 months) and OS
      (median 32 months). No statistical correlation was found between cell size and
      overall response (complete + partial remission), PFS (p = 0.38) or OS (p = 0.59),
      although a better trend was observed for the large cell group. A less favorable
      outcome was observed in patients in the high-intermediate + high risk groups,
      where median PFS and OS were 7 and 24 months, respectively, than in patients in
      the low + low-intermediate risk groups. No difference in response or outcome was
      detected between patients treated with the CHOP and the F-MACHOP regimens, while
      all 5 patients given high-dose chemotherapy and BMT are alive and in CR.
      INTERPRETATION AND CONCLUSIONS: Our experience shows that PTCL-U are rare
      lymphomas frequently having an aggressive presentation. The response to
      conventional polychemotherapeutic regimens like CHOP or F-MACHOP is generally
      poor, especially in those cases with advanced stage and a high-intermediate or
      high International Prognostic Index. The observation that all five patients who
      were treated with bone marrow transplantation are alive and in complete remission
      suggests using this strategy, particularly in young patients with a poor
      International Prognostic Index.

PMID- 9175322
TI  - Fibrinolytic parameters in patients undergoing total hip replacement:
      relationship with the development of asymptomatic deep vein thrombosis and
      diagnostic usefulness of venous occlusion.
AB  - BACKGROUND AND OBJECTIVE: It has been suggested that impaired fibrinolytic
      activity contributes to deep vein thrombosis in orthopedic surgery. Studying the
      fibrinolytic system following venous occlusion has been proposed as a good method
      of detecting the risk of this postoperative complication. The objective of this
      work was to verify whether venous occlusion represents a reliable method of
      detecting an impaired fibrinolytic response after total hip replacement. METHODS:
      Thirty-two consecutive patients undergoing total hip replacement were studied.
      Citrated blood samples were taken from each patient the day before surgery and on
      postoperative days 1, 3, and 7, before and after venous occlusion, in order to
      evaluate plasma levels of tissue plasminogen activator (t-PA) and plasminogen
      activator inhibitor (PAI-1). All patients underwent bilateral phlebography 10
      days after surgery. RESULTS: Seven out of 32 patients (21.9%) developed deep
      venous thrombosis (DVT) according to the venographic test. After surgery, an
      increase in t-PA antigen levels was detected both in patients who developed DVT
      and in those who did not, with a significant increase on the first and seventh
      days after surgery only in the non-DVT group. After 10-min venous occlusion, t-PA
      antigen levels increased at all postoperative recordings in both groups of
      patients, but most significantly on days 1 and 7 after surgery. PAI-1 antigen
      plasma levels, when measured before venous occlusion, increased only in non-DVT
      patients on the seventh postoperative day. After venous occlusion, a difference
      was found between the two groups only postoperatively on day 7 with regard to PAI
      1 levels. INTERPRETATION AND CONCLUSIONS: According to our results, no impaired
      fibrinolytic response was found in DVT patients. In addition, venous stasis seems
      to give no further information with respect to basal values in the early
      detection of postoperative thromboembolic complications in orthopedic patients.

PMID- 9175323
TI  - Small bowel infarction by Aspergillus.
AB  - Primary gut involvement by Aspergillus is a rare and often fatal complication of
      intensive antileukemic therapy. We describe the case of an adult patient affected
      by acute leukemia who developed a small bowel fungal thromboembolism without
      radiographic evidence of lung involvement during the post-induction aplastic
      phase. The diagnosis was made histologically at laparotomy performed for small
      bowel perforation. The patient died a week later in spite of amphotericin-B
      treatment and neutrophil recovery. Anti-Aspergillus prophylaxis and early
      introduction of amphotericin-B in the treatment of febrile neutropenia is
      probably advisable in all cases of AML.

PMID- 9175324
TI  - Development of CLL in individuals with mild lymphocytosis, without bone marrow
      infiltration, but with evidence of a monoclonally expanded population in
      peripheral blood.
AB  - Mild lymphocytosis (< 10 x 10(9)/L) is a common finding in routine blood tests.
      When it persists, it raises the question of whether this disorder is an early
      manifestation of chronic lymphocytic leukemia (CLL). If it is accompanied by bone
      marrow infiltration, it can be safely considered as a sign of CLL. The aim of
      this study was to analyze retrospectively the usefulness of immunophenotyping and
      immunogenotyping for early detection of lymphocyte clonality in ambiguous cases
      of lymphocytosis without bone marrow infiltration. Twenty-six healthy
      individuals, 47 to 77 years old, with an absolute lymphocyte count (ALC) at the
      "onset" of the disorder between 4 x 10(9)/L and 9 x 10(9)/L, without marrow
      infiltration, were studied and followed for a period of 31 to 51 months. CD19,
      CD20, CD5, CD2, CD4, CD8 surface markers and amplification of the Ig heavy chain
      CDR-3 locus were used for immunophenotypic and genotypic analysis, respectively.
      Our studies indicate that immunophenotyping alone is sufficient and superior to
      CDR-3 locus amplification for the early detection of lymphocyte clonality in
      peripheral blood. Furthermore, the high frequency of CLL development in
      individuals with established monoclonality strongly suggests that patients with
      mild borderline lymphocytosis, even without bone marrow infiltration, have to be
      followed for progression to CLL and its possible complications.

PMID- 9175325
TI  - Effects of macrophage- and granulocyte-colony stimulating factors on thymidylate
      synthase and thymidine kinase activity in rat hematopoietic cells.
AB  - The effects of macrophage (M) and granulocyte (G) colony-stimulating factors
      (CSFs) on the activity of thymidylate synthase and thymidine kinase, which are
      involved in de novo and salvage pathways for pyrimidine nucleotide synthesis,
      were investigated in the hematopoietic cells of rats treated with
      cyclophasphamide. Thymidine kinase activity, but not that of thymidylate
      synthase, was markedly enhanced in these cells by M- and G-CSF treatment (p <
      0.05 and p < 0.01). G-CSF directly, and M-CSF indirectly stimulate myeloid cells
      and lead to S-phase predominantly via the salvage pathway for pyrimidine
      nucleotide synthesis. The present study indicates that these CSFs can be
      effective inducers of complete remission in acute leukemias when employed
      together with chemotherapy.

PMID- 9175326
TI  - Platelet and monocyte variables in homocystinuria due to cystathionine-beta
      synthase deficiency.
AB  - To gain insight into the mechanisms responsible for enhanced thromboxane (TX) A2
      biosynthesis in homozygous homocystinuria due to cystathionine-beta-synthase
      deficiency (CBSD), we measured a series of platelet and monocyte variables in 9
      homozygous and 8 obligate heterozygous CBSD patients and evaluated their
      relationships to thromboxane formation, as reflected by urinary excretion of its
      major metabolite, 11-dehydro-TXB2 (TXM). Consistent with our previous data,
      homozygous CBSD patients showed abnormally high TXM excretion (1175 +/- 236 pg/mg
      creatinine vs. 284 +/- 39 in control subjects; p < 0.001). Significantly higher
      TXM excretion was also found in obligate heterozygotes (755 +/- 450 pg/mg
      creatinine; p < 0.05 vs. control subjects). All platelet and monocyte variables
      fell within the normal range in CBSD patients and none showed a correlation with
      TXM excretion (p always > 0.05). Our results argue against abnormalities of
      platelet and monocyte function being responsible for the abnormally high in vivo
      TXA2 biosynthesis in homocystinuria due to CBSD.

PMID- 9175327
TI  - The molecular basis of myelodysplastic syndromes.
AB  - BACKGROUND AND OBJECTIVE: The myelodysplastic syndromes comprise a heterogeneous
      group of neoplastic disorders characterized by ineffective hematopoiesis with an
      increased tendency to evolve to acute leukemia. Clinically, the common
      manifestations include peripheral blood cytopenias of one or more lineages and a
      normal to hyperplastic marrow. MDS has been defined on the basis of morphological
      criteria, namely the percentage of blast cells in the bone marrow, by the French
      American-British study group. Scoring systems have been developed to include such
      factors as hemoglobin, leukocyte count and age in the evaluation of MDS
      prognosis. Although useful in the prediction of clinical course and design of
      therapy regimens, our understanding of the basis of MDS has come from recent
      advances in molecular analysis of these disorders. This review describes some of
      the established and recent contributions to our understanding of the molecular
      basis of the myelodysplastic syndromes. EVIDENCE AND INFORMATION SOURCES: The
      authors of the present review have been working in the field of myelodysplastic
      syndromes for several years and have contributed original papers on the molecular
      pathogenesis of these disorders. In addition, in the present review they have
      critically examined articles and abstracts published in journals covered by the
      Science Citation Index and Medline. STATE OF ART AND PERSPECTIVES: Cytogenetic
      anomalies and proto-oncogene abnormalities point to new understanding of the
      pathogenesis of MDS as a sequence of DNA lesions leading to the evolution of the
      pre-malignant clone. The prognostic significance of these factors in predicting
      leukemic transformation and survival remains controversial. Characterization of
      MDS cells in vitro in response to combinations of exogenous growth factors have
      not only provided valuable information regarding ineffective hematopoiesis in MDS
      but have provided a new insight into treatment of MDS. One major development in
      our understanding of MDS is the possible explanation for the apparent paradox of
      a cellular marrow in combination with peripheral cytopenias. Extensive premature
      programmed cell death or apoptosis has been reported to be at least partly
      responsible. It will remain to be seen whether this fundamental characteristic of
      myelodysplastic hematopoiesis will play a central role in the drug or genetic
      based therapy in the myelodysplastic syndromes.

PMID- 9175328
TI  - CD10 in acute leukemias. GEIL (Groupe d'Etude Immunologique des Leucemies).
AB  - BACKGROUND AND OBJECTIVE: CD10, initially known as cALLA, was identified as one
      of the earliest markers expressed by leukemic cells of the lymphoblastic lineage.
      This review summarizes what has been discovered about this ubiquitous molecule
      since anti-cALLA antibodies allowed its detection on leukemic cells. It also
      attempts to specify the selectivity of CD10 in acute leukemias as a
      subclassification or prognostic tool. EVIDENCE AND INFORMATION SOURCES: The
      material used for this review includes articles identified as relevant through a
      meta-analysis in the Medline database, as well as personal publications or data
      issued within the French Study Group on the Immunology of Leukemias (GEIL). STATE
      OF ART: CD10 now stands as much more than a mere leukemic marker. It belongs to a
      rather large family of exopeptidases expressed in a variety of tissues and mostly
      involved in the activation or deactivation of peptides through the removal of
      terminal amino acids. CD10 expression on leukemic cells remains a useful
      subclassification tool for B-lineage leukemias, but it can also be found on other
      types of leukemic cells. PERSPECTIVES: Much remains to be discovered regarding
      the physiological role of CD10 during the maturation of normal B-lineage
      lymphocytes and about its functions-or lack of activity-on leukemic cells. It
      could also provide a valuable tool for further dissecting B-lineage leukemias
      when the quantitative aspect of its expression on blast cells is taken into
      account.

PMID- 9175329
TI  - Hyperhomocysteinemia and venous thromboembolic disease.
AB  - BACKGROUND AND OBJECTIVE: In spite of the large number of reports showing that
      hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and
      arterial occlusive disease, this metabolite of the methionine pathway is measured
      in relatively few laboratories and its importance is not fully appreciated.
      Recent data strongly suggest that mild HHcy is also involved in the pathogenesis
      of venous thromboembolic disease. The aim of this paper is to analyze the most
      recent advances in this field. EVIDENCE AND INFORMATION SOURCES: The material
      examined in the present review includes articles and abstracts published in
      journals covered by the Science Citation Index and Medline. In addition the
      authors of the present article have been working in the field of mild HHcy as
      cause of venous thromboembolic disease. STATE OF ART AND PERSPECTIVES: The
      studies examined provide very strong evidence supporting the role of moderate
      HHcy in the development of premature and/or recurrent venous thromboembolic
      disease. High plasma homocysteine levels are also a risk factor for deep vein
      thrombosis in the general population. Folic acid fortification of food has been
      proposed as a major tool for reducing coronary artery disease mortality in the
      United States. Vitamin supplementation may also reduce recurrence of venous
      thromboembolic disease in patients with HHcy. At the present time, however, the
      clinical efficacy of this approach has not been tested. In addition, the bulk of
      evidence indicates that fasting total homocysteine determinations can identify up
      to 50% of the total population of hyperhomocysteinemic subjects. Patients with
      isolated methionine intolerance may benefit from vitamin B6 supplementation.
      Homocysteine-lowering vascular disease prevention trials are urgently needed.
      Such controlled studies, however, should not focus exclusively on fasting
      homocysteine determinations and folic acid monotherapy.

PMID- 9175330
TI  - Allogeneic hematopoietic stem cells from sources other than bone marrow:
      biological and technical aspects.
AB  - BACKGROUND AND OBJECTIVE: Identification and characterization of hematopoietic
      stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible
      alternatives to conventional allogeneic bone marrow (BM) transplantation. The
      growing interest in this use of allogeneic stem cells has prompted the Working
      Group on CD34-positive Hematopoietic Cells to review this subject by analyzing
      its biological and technical aspects. EVIDENCE AND INFORMATION SOURCES: The
      method used for preparing this review was informal consensus development. Members
      of the Working Group met three times, and the participants at these meetings
      examined a list of problems previously prepared by the chairman. They discussed
      the individual points in order to reach an agreement on the various concepts, and
      eventually approved the final manuscript. Some of the authors of the present
      review have been working in the field of hematopoietic stem cell biology and
      processing, and have contributed original papers published in peer-reviewed
      journals. In addition, the material examined in the present review includes
      articles and abstracts published in journals covered by the Science Citation
      Index and Medline. STATE OF ART: Several studies have now shown that
      hematopoietic stem cells collected from peripheral blood after the administration
      of G-CSF, or from cord blood upon delivery, are capable of supporting rapid and
      complete reconstitution of BM function in allogeneic recipients. Perhaps more
      importantly, reinfusion of large numbers of HLA-matched T-cells from PB
      collections or T-cells with various degrees of HLA disparity from CB did not
      result in a higher incidence or greater severity of acute graft-versus-host
      disease than expected with BM. Based on the data reviewed, operative guidelines
      for mobilization, collection and graft processing are provided. PERSPECTIVES: It
      should be remembered that despite the growing interest, these procedures must be
      still considered as advanced clinical research and should be included in formal
      clinical trials aimed at demonstrating their definitive role in stem cell
      transplantation. In this regard, a large European randomized study is currently
      comparing PB and BM allografts. However, the possibility of collecting large
      quantities of hematopoietic progenitor-stem cells, perhaps with reduced allo
      reactivity, offers an exciting perspective for widening the number of potential
      stem cell donors and greater leeway for graft manipulation than is possible with
      BM.

PMID- 9175331
TI  - Potential clinical applications of rhGM-CSF in acute myeloid leukemia based on
      its biologic activity and receptor interaction.
AB  - BACKGROUND AND OBJECTIVE: Granulocyte-macrophage colony-stimulating factor (GM
      CSF) is a multilineage hemopoietic growth factor that stimulates proliferation,
      differentiation, and survival of progenitor cells, enhances the functional
      activities of mature myeloid effector cells, and plays a key role in host defense
      and the inflammatory process. Although the clinical use of rhGM-CSF in patients
      affected by lymphoid malignancies is widely accepted, its utility and safety in
      the management of acute myeloid leukemia (AML) and myelodysplastic syndromes
      (MDS) is still controversial. The three main schedules adopted for clinical
      application of GM-CSF in AML are as follows: A) post-chemotherapy, in order to
      shorten the duration of neutropenia and/or monocytopenia; B) prechemotherapy to
      recruit blast cells into active cell cycle phases, and to increase their
      sensitivity to cell cycle-dependent cytotoxic drugs; C) as a mobilizing agent to
      induce the release of progenitor cells from bone marrow into circulation
      (peripheral blood progenitor cell transplantation-PBPC). The objective of this
      paper is to analyze the potential clinical applications of rhGM-CSF in AML.
      EVIDENCE AND INFORMATION SOURCES: The material examined in the present review
      includes several personal papers in this field and articles and abstracts
      published in journals covered by the Science Citation Index. STATE OF THE ART:
      Based on current knowledge, it may be argued that rhGM-CSF should be used only in
      a subset of AML patients at high risk of infection mortality, including elderly
      subjects, and/or in those AML patients who relapse or are resistant to induction
      treatment. However, the risk of stimulating the leukemic clone following GM-CSF
      therapy should be kept in mind when using this growth factor in the clinical
      setting, even though the great majority of the reported papers on this subject
      have shown that GM-CSF therapy does not affect relapse rates, frequency of
      remissions or patient life expectancy. PERSPECTIVES: It is likely that new data
      from controlled clinical trials will clarify the therapeutic role of GM-CSF in
      myeloid-derived malignancies, allowing the establishment of consensus guidelines
      for its use.

PMID- 9175332
TI  - Methodological aspects of total plasma homocysteine measurement.

PMID- 9175333
TI  - A case of acute myeloid leukemia with renal mass.

PMID- 9175334
TI  - Leukocyte-endothelial cell interactions and vascular injury in the earliest
      preclinical stages of atherosclerosis.

PMID- 9175335
TI  - Rapid disease progression in two cases of myelodysplastic syndrome (MDS)
      following short therapy with G-CSF.

PMID- 9175337
TI  - Mental health and moral integrity.

PMID- 9175336
TI  - Chlamydia pneumoniae pneumonia with acute hemorrhagic pericarditis in patient
      with acute leukemia.

PMID- 9175338
TI  - A personality disorder of excessive power strivings.
AB  - None of the existing formal diagnostic categories in psychiatry today addresses
      adequately the issues of excessive power-seeking, corruption and destructiveness.
      Excessive power strivings both poison the personality of the individual who is
      obsessed in his spirit and mind with power and do unacceptable harm to other
      peoples' lives. The present proposal of a diagnostic category of a Personality
      Disorder of Excessive Power Strivings is intended to fit into current diagnostic
      schema of DSM as well as into an earlier proposal (1) to examine in all
      psychopathology not only the burdens and damage people do and impose on their own
      selves and their own functioning, but also the harm they do to other peoples'
      lives and functioning. The diagnosis is to be used when the individual displays
      prolonged and severe manifestations of the following listed criteria: The basic
      feature which is always present in this personality disorder is: 1. Intense and
      extensive power strivings. In addition, at least three other of the following
      characteristics should be present; 2. Lack of empathy for people, and
      indifference to the suffering of others; 3. "Street smart" alertness and
      remarkable cunning committed to seizing and expanding power; 4. Ruthlessness in
      cultivation of power; 5. Scapegoating and projection of blame on to targeted
      individuals or a group, an insistent need to identify certain others as lowly,
      worthless and intended victims; 6. Corruption by power and addiction to power; 7.
      Demands of other people to be dependent on one's powerful personality, or that
      they become one's obedient followers; 8. Emphasis on symbolisms of pure vs.
      impure, holy vs. infidel, chosen vs. condemned; 9. A basic disrespect for the
      lives of others evidenced in callous or indifferent exposure of others to undue
      risks; 10. An absence of conscience in contexts of self-interest and opportunity;
      11. A homicide/suicide orientation.

PMID- 9175339
TI  - Ethical issues in the therapeutic community.
AB  - The development of ethical standards in psychiatry has been largely during the
      past 30 years. Psychotherapy poses particular problems of an ethical nature and
      the therapeutic community with its apparent lack of professional distance between
      patients and professionals is a situation in which unethical practices could, and
      sometimes do develop. Nevertheless, the very nature of the close contact between
      professionals and patients in the therapeutic community can be a fruitful medium
      for the generation of a system of values and moral behavior in patients provided
      the professional staff are themselves aware of the inherent dangers and build in
      appropriate safeguards.

PMID- 9175340
TI  - The patient as moral agent in psychotherapy.
AB  - Psychotherapists may be uncertain whether the morality of the patient is their
      concern. Philosophically, we can distinguish between two kinds of morality:
      relativistic and universal. Relativistic morality is concerned with the
      conventions of a particular society and is authoritarian in nature. Universal
      morality is common to all humanity and is innate and autonomous. We can identify
      the two kinds of morality in psychological theory, representing stages of
      development. Psychoanalysis may facilitate a movement from authoritarian
      (relativistic) to autonomous (universal) morality. I shall argue that universal
      morality is relevant in psychotherapy. On the other hand, the therapist might
      help patients to question and reconsider their adherence to conventional codes.

PMID- 9175341
TI  - The ethical issues of enforcing parents' participation in the psychiatric
      treatment of minors.
AB  - Currently, when parents do not comply with the recommended psychiatric treatment
      for their child through the Mental Health Act, the mental health practitioner and
      the statutory social worker are faced with unclear guidelines as to how best to
      respond. Under the Israeli Mental Health Act and the existing Youth Law, there
      are no effective means of enforcing parental involvement in the psychiatric
      treatment of "at risk" minors. Non-involvement may seriously compromise the
      assessment and treatment of these minors, resulting in ongoing risk of
      developmental damage. Proposed changes in the current Youth Law include ratifying
      means of enforcing parental involvement. Ethical issues regarding such a proposal
      are discussed using a case vignette. Clinical guidelines for parental
      participation in minors' psychiatric treatment are discussed.

PMID- 9175342
TI  - A dialogue between descendants of Holocaust perpetrators and victims--session
      two.
AB  - The legacy of the Holocaust lingers on, continuing to have a marked and pervasive
      effect on the survivors-and their second, third and fourth generation
      descendants. This is now well documented in the professional literature, in
      novels, on film and in museums. What has been virtually non-existent is activity
      which brings together the descendants of perpetrators and of victims to interact
      and move toward some rapprochment in the here and now, and for the future, and a
      literature documenting and analyzing such activity. This article describes a
      second dialogue session between German and Israeli mental health professionals,
      all of whom are descendants of survivors and/or are treating such descendants.
      This meeting was held during the International Family Therapy Association
      Congress in Guadalajara, Mexico, in October 1995, and some Mexican colleagues who
      had inherited the Holocaust legacy also participated, as did several others from
      Sweden and the United States. The interchanges about their memories and deeply
      entrenched feelings were heated, emotional and profound. All involved indicated
      they had experienced great anguish about coming, and in being present, and that
      during the session they felt some relief and gained some understanding of the
      "other." They urged continuation of this dialogue process, begun during a
      conference in Budapest, Hungary, in 1994.

PMID- 9175343
TI  - Some sociopsychological and political perspectives of the meaning of the
      Holocaust: a view from Israel.
AB  - On the background of some psychological, social and political reactions to the
      Holocaust over the last 40 years, this paper focuses on the meaning of the
      Holocaust as it is woven into the social and political fabric of Israel today.
      The Palestinian-Israeli conflict receives special emphasis in this context.
      Through a psychoanalytic lens, the motivations leading both to the denial of the
      Holocaust and its usage in different areas of political life is examined; the
      usage taking place on different levels on the continuum conscious-unconscious.
      Such usage as well as its consequences encourage a holding on to rigid positions
      and to the past; this comes at the expense of dealing effectively with the
      present. Such patterns of behavior are in this way social mechanisms analogous to
      the well-known unconscious psychological mechanisms of defense. They are akin to
      other psychological phenomena, such as the repetition compulsion and the
      mechanism of psychological deployment. Clinical and social illustrations of these
      phenomena are given.

PMID- 9175344
TI  - Hospitalized mentally ill patients in Israel vote for the first time.
AB  - For the first time in Israel, hospitalized mentally ill patients were enabled to
      participate in the election of the prime minister and members of the Knesset
      (Israeli parliament) held on May 29, 1996. In a demonstration election held in
      Yehuda Abarbanel Hospital to teach and prepare the patients to vote, the outcome
      of the vote for the prime minister was identical to the results of the general
      public vote. The sample vote results for members of the Knesset were slightly
      different from those in the actual election. The character of the voting in this
      sample bolsters arguments for the rights of mentally ill individuals to
      participate in the basic democratic process of voting and should ease any
      misgivings felt by some of the public about their ability to vote as rationally
      as other members of the public.

PMID- 9175345
TI  - The abuse of psychodynamic diagnostics and therapeutic techniques.

PMID- 9175346
TI  - Dental materials: 1995 literature review.
AB  - This critical review of the published literature on dental materials for the year
      1995 has been compiled by the Dental Materials Panel of the United Kingdom. It
      continues the series of annual reviews started in 1973 and published in the
      Journal of Dentistry. Emphasis has been placed upon publications which report
      upon the materials science or clinical performance of the materials. The review
      has been divided by accepted materials classifications (fissure sealants, glass
      polyalkenoate cements, resin composites, dentine bonding, dental amalgam,
      endodontic materials, casting alloys, investment materials, resin-bonded bridges
      and ceramo-metallic restorations, all ceramic restorations, denture base and soft
      lining materials, impression materials, dental implants, orthodontic materials
      and biomechanics). Three hundred and thirty articles published in 68 titles have
      been reviewed.

PMID- 9175347
TI  - The use of powdered gloves in dental practice: a cause for concern?
AB  - OBJECTIVES: To critically review the potential hazards associated with the use of
      powdered, natural rubber latex (NRL) gloves in dental practice and to report some
      practical difficulties which may be encountered when handling dental materials
      with powdered NRL gloves. DATA SOURCES: Articles published in the international
      literature over the last 10 years. STUDY SELECTION: A number of recent studies in
      the medical and surgical literature have confirmed that NRL proteins leach out of
      latex gloves and bind to surgical glove powders. The most serious, potential
      hazard associated with the continued use of powdered NRL gloves in dental
      practice is that of latex sensitization by exposure to aerosolized NRL proteins.
      Hand dermatitis is now recognized as an occupational hazard in dentistry and has
      been associated with the continuous wearing of protective gloves. Studies, in the
      dermatological literature, have suggested that glove powders may exacerbate an
      irritant dermatitis and enhance the potential for adverse reactions to other
      components of NRL gloves. The surgical literature has already highlighted the
      risks of post-operative granuloma formation, due to glove powder contamination of
      the surgical wound. The possible effects of powder contamination of dental
      implant sites, on the outcome and success of implants has yet to be established.
      Recent in vitro studies have investigated the effect of latex glove contamination
      on the shear-bond strength of porcelain laminate veneers: one study demonstrated
      that starch powder significantly affected the bond strength, whereas the other
      showed that latex glove contamination of the porcelain surface did not have any
      significant effect. Long-term, in vivo studies are now required. CONCLUSIONS:
      Dental practitioners should consider the potential health risks which are
      associated with the use of powdered NRL in dental practice. Powder contamination
      may affect the long-term results and success of clinical procedures in dentistry.

PMID- 9175348
TI  - Efficacy of digital intra-oral radiography in clinical dentistry.
AB  - OBJECTIVES: This article emphasizes the comparison of intra-oral digital imaging
      to film-based imaging. Additional possibilities of digital imaging that may
      contribute to system efficacy are discussed as well. STUDY SELECTION: The main
      subjects for research in digital imaging are image quality, image acquisition,
      diagnostic quality, image manipulation, automated analysis, and application
      software. DATA SOURCES: Representative articles on these subjects from the
      international literature are used for this review. Indirect digital imaging still
      requires film processing, sophisticated film digitizers, and time to digitize
      film. Although it is not an efficient method for the dental practice,
      digitization can be very useful for quantitative analysis of radiographs. Direct
      digital imaging is more efficient than indirect digital imaging. The main
      advantages are (semi) real time imaging, low X-ray dose requirements, and no need
      for chemical processing. In spite of a more limited resolution of the images,
      direct imaging may perform as accurately as film-based imaging. Direct image
      plate systems can well be used, for instance, for full-mouth series. The main
      application of direct sensor systems appears to be endodontology and
      implantology. In summary, direct digital imaging may be as efficient as film
      based imaging in clinical dentistry. The computer provides for many additional
      options in digital imaging, such as the digital storage, compression, and
      exchange of radiographic information. Image manipulation (e.g. image enhancement,
      subtraction radiography and image reconstruction) and automated analysis may
      benefit radiodiagnosis. CONCLUSION: It can be concluded that digital imaging
      certainly has great potential, especially with respect to improvement of
      diagnostic quality and automated image analysis.

PMID- 9175350
TI  - A 4-year retrospective clinical study of Class I and Class II composite
      restorations.
AB  - OBJECTIVES: The purpose of this study was to determine the longevity and quality
      of Class I and Class II resin composite (Herculite XR) restorations placed in
      private practice. METHODS: One thousand two hundred and nine Class I and Class II
      composite restorations with margins in enamel were evaluated clinically after
      periods of between 12 months and 4.5 years in clinical service by two calibrated
      examiners using a modified version of established criteria. RESULTS: Of the
      restorations investigated 94.8% were rated as 'good' (Alpha 79.3%) or 'clinically
      acceptable' (Bravo 15.5%). Significantly more restorations in premolar teeth were
      rated as Alpha (82%) than in permanent molar teeth (77%). The survival rate after
      4 years was around 87%. The 50% survival-time, calculated by extrapolation
      according to Weibull, was approximately 9 years. CONCLUSIONS: It is concluded
      that the composite investigated is an appropriate material for the restoration of
      Class I and Class II lesions with margins located in enamel in premolar and
      permanent molar teeth.

PMID- 9175349
TI  - Long-term survival of extensive amalgams and posterior crowns.
AB  - OBJECTIVES: There is very little information available from private dental
      practices on the comparative survivals of extensive posterior amalgam
      restorations and posterior crowns placed in the same patient population.
      Therefore, the present retrospective study examined the performance of such
      restorations at three long-established Adelaide city practices. METHODS: Life
      table survival estimates were generated for 160 extensive amalgams, 96 cast gold
      crowns and 174 ceramometal crowns. The restorations were placed by 20 dentists at
      various times in 100 patients who attended the practices on a regular basis for
      around 25 years on average. RESULTS: There were no significant differences found
      in the survival times for both types of crowns, with around 70% still being
      present at 20 years. However, the median survival time for the extensive amalgams
      was much lower, at 14.6 years. Despite these differences in survival times, the
      extensive amalgam restorations survived for longer than is usually expected.
      CONCLUSION: In this present study, the survival findings have implications for
      the most cost-effective dental treatments of large lesions in posterior teeth.

PMID- 9175351
TI  - The reasons for tooth extractions in adults and their validation.
AB  - OBJECTIVES: To investigate the primary reasons for the extraction of permanent
      teeth in adults and to validate the dentists' reasons for extraction. METHODS:
      Twenty-one dentists in the Greater Manchester area took part in the study. These
      dentists provided extracted teeth stored in 10% buffered formal saline together
      with details of the patient's age, sex, dental attendance pattern and the reason
      for extraction. In order to validate the reasons for extraction, teeth were
      examined for the presence or absence of coronal and root caries. A subgroup of 80
      teeth, half of which were extracted primarily for caries and half for periodontal
      reasons were selected, stained and attachment loss measured at six sites per
      tooth to validate periodontal reasons for extraction. RESULTS: Three hundred and
      eighty-nine teeth were collected of which 37% were extracted primarily due to
      caries and 29% due to periodontal disease. Caries was the main reason for
      extraction in patients under 50 years, whereas periodontal disease was the
      commonest reason in the over-50 age group. Irregular attenders had more
      extractions for caries than regular attenders but attendance pattern did not
      affect the proportion of teeth extracted for periodontal reasons. The mean
      greatest loss of attachment on teeth extracted for periodontal reasons was 12 mm
      compared with 6.5 mm for caries. CONCLUSION: In this group of patients caries was
      the most common reason for extraction of teeth but periodontal disease became a
      more important reason for extraction after 50 years of age. The study validated
      the dentists' given reason for extraction.

PMID- 9175353
TI  - Shear bond strengths produced by composite and compomer light cured orthodontic
      adhesives.
AB  - OBJECTIVES: To test the shear bond strengths obtained when orthodontic brackets
      were bonded ex vivo using a composite resin and a compomer orthodontic adhesive.
      METHODS: Specimens were tested in a special jig made to fit an Instron testing
      machine. After debonding, the adhesive remaining on bracket bases and enamel
      surfaces was mapped. RESULTS: Bond strengths ranged from 8 to 23 MPa with the
      composite resin producing higher strengths than the compomer for similar
      combinations of variables. Bond strength was increased by longer curing and a
      longer debond interval and was higher for brackets with mesh bases than undercut
      bases. More compomer remained on the enamel surface after debonding than did the
      composite resin. CONCLUSION: The compomer produced bond strengths within the
      range considered to be clinically acceptable in other studies. If it was
      clinically successful as an orthodontic adhesive a compomer would confer the
      advantage that fluoride release would help to minimize the onset of early caries
      around bonded brackets.

PMID- 9175352
TI  - Long-term survival data from a clinical trial on resin-bonded bridges.
AB  - OBJECTIVES: A clinical trial, involving 203 resin-bonded bridges (RBBs) was
      undertaken to investigate the influence of retainer-type and luting material on
      the survival of these restorations. METHODS: For this evaluation, 157 patients
      were available (14% of the original sample was lost to follow-up or excluded from
      the study following the stopping criteria). Fifty per cent of the patients were
      questioned concerning the fate of the RBBs and 59% of questioned patients were
      examined clinically. The patients that were seen for examination were
      representatives of the experimental groups. The findings from the clinical
      examination were compared with the data obtained from the questionnaire. Missing
      data were censored at the date of the last available information. Kaplan-Meier
      estimates were calculated to assess the survivals at the endpoints and compared
      using Cox's proportional hazards procedure. RESULTS: A significant difference was
      found between perforated (P-type) and etched (E-type) RBBs (P = 0.05) for
      original bonded restorations but not when rebonded RBBs were taken into account.
      The results of the survival analysis were: anterior P-type, 49 +/- 7% after 10.5
      years: anterior E-type, 57 +/- 7% after 10.5 years; posterior P-type, 18 +/- 11%
      after 6.8 years; posterior E-type, 37 +/- 13% after 10.2 years. Survivals of RBBs
      that were rebonded once during the evaluation period were 62 +/- 9% (11.0 years)
      for anterior RBBs and 51 +/- 11% (10.2 years) for posterior RBBs. CONCLUSIONS:
      The factor location (anterior versus posterior) was as in previous analyses,
      highly significant. Differences in survival between cementation materials were
      not significant.

PMID- 9175354
TI  - The effect of chairside relining materials on rat palatal mucosa.
AB  - OBJECTIVES: To investigate the effects of denture relining materials on oral
      mucosa in vivo in a rat model. METHODS: Denture-like appliances covering the
      palate in Wistar rats were relined with a resilient soft linting material and a
      hard 'chairside' relining material. The effects on the palatal epithelium were
      studied by quantitative analysis using computerized planimetry. RESULTS: The
      relining materials caused an increase in the thickness of the keratinized layer,
      while not increasing the total epithelial thickness. CONCLUSIONS: Relining
      materials are not totally without effect on oral mucosa. Further in vivo research
      is indicated.

PMID- 9175355
TI  - Restoration-related salivary Streptococcus mutans level: a dental caries risk
      factor?
AB  - OBJECTIVES: The salivary level of Streptococcus mutans related to filled teeth
      was compared with the levels related to decayed and sound teeth, in order to
      establish whether the presence of restorations may increase the risk of infection
      of other teeth by Streptococcus mutans. METHODS: The sound, decayed and filled
      teeth were recorded in 809, 6-7-year-old school-children. Salivary Streptococcus
      mutans detection (i.e. more than 1 x 10(4) CFU/ml) and counts were evaluated.
      Streptococcus mutans log count means and prevalence values of subjects with only
      sound teeth (group 1), with filled, without decayed teeth (group 2), with
      decayed, without filled teeth (group 3), were calculated and compared using the
      Student's t-test and the chi-square test. The effect of filled, decayed and sound
      teeth on Streptococcus mutans level was also evaluated using logistic regression.
      RESULTS: Log count means and prevalence values of group 2 subjects were
      significantly lower than values of group 3 subjects (means, 0.92 vs 1.66:
      prevalence, 73.17% vs 94.63%) and statistically not-different from values of
      group 1 subjects (mean. 0.75: prevalence, 70.06%). The logistic regression
      analysis showed that the factors significantly increasing the risk of
      Streptococcus mutans being detected in saliva were only primary and/or permanent
      decayed teeth. The risk of Streptococcus mutans being detected in saliva was not
      affected by filled teeth more than sound teeth. CONCLUSIONS: In the present study
      population, the salivary Streptococcus mutans level attributable to filled teeth
      was low; this suggests that treatment of a carious lesion would cause a lowering
      of Streptococcus mutans concentration to the same levels as those shown by
      healthy subjects, thus reducing the risk of infection to other teeth.

PMID- 9175356
TI  - In vitro peel/shear bond strength of orthodontic adhesives.
AB  - OBJECTIVES: The purpose of this study was to evaluate the in vitro peel/shear
      bond strength of a selection of orthodontic bracket adhesives to human premolar
      teeth. METHODS: Twenty-two commercially available bracket adhesives were used to
      bond the same bracket type (Miniature Twin, 3M Unitek, Monrovia, CA. USA) on 264
      intact human premolar teeth and then adhesively tested to failure. Peel/shear
      bond strength values were calculated in newtons and megapascals. The site of bond
      failure was scored according to the Adhesive Remnant Index. Statistics included
      one-way analysis of variance and Tukey's Studentized Range test together with
      Weibull analysis. The latter is a survival analysis able to describe the
      performance of a material. RESULTS: The mean bond strengths varied from 9.9 MPa
      for Concise to 4.1 MPa for Heliosit Orthodontic. The overall F-test showed a
      significant difference (P < 0.0001). No significant differences in bond strength
      were found between Concise, AccuBond, Imperva Dual, Transbond XT, Kurasper and
      Spectrum. CONCLUSION: Concise and AccuBond are among the materials of choice for
      bonding fixed orthodontic appliances to teeth. These materials combine high bond
      strength with a reliable bond that is easily and quickly debonded.

PMID- 9175357
TI  - In vitro peel/shear bond strength evaluation of orthodontic bracket base design.
AB  - OBJECTIVES: The adhesive capacity of 17 different bracket types was evaluated in
      an in vitro peel/shear test. METHODS: Silane-treated metal bars were used as
      substrates with all bonding being performed using the orthodontic adhesive
      Concise. The effect of aluminium oxide air abrasion on the bonding performance of
      recycled metal bracket bases was evaluated. Morphological examination of the
      bracket bases was carried out under scanning electron microscopy. Statistics
      analysis included one-way ANOVA with Tukey's Studentized Range Test, two-way
      ANOVA and Weibull analysis. RESULTS: Mean peel/shear bond strength values range
      from 13.9 MPa for Allure Accu Arch, a ceramic bracket type, to 1.6 MPa for the
      plastic bracket CeramaFlex Advant Edge. Allure Accu Arch performed the best of
      all the ceramic brackets. However, bracket wing fracture was observed. The metal
      brackets Mini masters and Omni Arch showed no significant difference in bond
      strength compared with the ceramic bracket Allure Accu Arch (P < 0.01).
      CONCLUSION: The type of the bracket base determines its adhesive capacity.
      Sandblasting the base of recycled metal brackets had no uniform effect.

PMID- 9175359
TI  - Effect of acidic primers on bonding between stainless steel and auto-polymerizing
      methacrylic resins.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of acidic
      primers on bonding between methacrylic resins and SUS 316 stainless steel.
      METHODS: The primers were single liquid metal conditioners containing either a
      phosphate monomer (Cesead opaque primer, CO; Metal primer, MP) or a carboxylic
      monomer (Super-Bond liquid, SB; Acryl bond, AB; MR bond, MR). Disk metal
      specimens were air-abraded with alumina followed by priming. The disks were
      bonded with a methacrylic resin using a brush-dip technique (Super-Bond C & B, CB
      or Repairsin, RE). Specimens were thermocycled in water and bond strengths were
      determined. RESULTS: Shear bond strengths after the thermocycling were 11.9 MPa
      for CO-CB, 7.6 MPa for CO-RE, 4.9 MPa for SB-RE, 3.9 MPa for MP-RE, 3.3 MPa for
      AB-RE, 2.5 MPa for MR-RE, 1.9 MPa for None-CB, and 0 MPa for None-RE. The two
      systems primed with CO primer showed greater bond strengths than the other groups
      (P < 0.05). Of the two systems conditioned with CO primer, CB resin demonstrated
      higher value bond strength as compared with RE resin (P < 0.05). CONCLUSION:
      Among the systems examined, CO primer used together with CB resin exhibited
      greater bond strength to SUS 316 stainless steel than other systems after the
      ageing test. Reduction in bond strength by thermocycling, however, was remarkable
      for all groups.

PMID- 9175358
TI  - Knowledge and attitudes of Japanese dental health care workers towards HIV
      related disease.
AB  - OBJECTIVE: The present study was undertaken to investigate knowledge of AIDS and
      HIV infection among Japanese dental health care workers, the source of that
      knowledge and attitudes of dental workers towards infected patients. METHODS: The
      study population surveyed by means of a self-administered questionnaire consisted
      of 174 dental health workers at Nagasaki University Dental Hospital, including
      students and trainee hygienists. RESULTS: Most respondents (100% response)
      claimed their major source of AIDS knowledge to be derived from the media. Almost
      all considered their knowledge of AIDS and HIV infection to be more than moderate
      but still inadequate. The majority of respondents would be hesitant about
      performing dental treatment on HIV-positive patients. It was widely anticipated
      that dental patients infected with HIV would increase in the next few years and
      many were anxious about the increasing occupational risk of HIV infection. Only
      22.4% of respondents had the same attitude towards treating HIV-positive and HIV
      negative patients. Most also considered that they would be able to take care of
      the oral opportunistic diseases associated with HIV. Over 90.0% of respondents
      requested additional education about HIV, particularly information about the
      prevention and spread of the virus and cross-infection requirements. CONCLUSION:
      It is concluded that further training in the medical and psychological aspects of
      treating HIV-positive patients is indicated in Japan.

PMID- 9175360
TI  - In vitro dentine fluoride uptake from three fluoride-containing composites and
      their acid resistance.
AB  - OBJECTIVES: The purpose of this study was to determine the dentine fluoride
      uptake from three fluoride-containing composites (FluorEver, FluoroCore and
      Pertac-Hybrid) and to investigate their ability to affect the resistance of
      dentine to an artificial caries challenge. METHODS: Three dentine slabs were
      prepared from each tooth. The baseline, total and bound fluoride concentrations
      of each tooth were determined by three successive abrasion biopsies performed on
      each slab followed by adjusting to standardized depths of 10 microns. Next,
      dentine slabs ligated with the composites were suspended in synthetic saliva for
      1 week. After removal of the composites, these specimens and controls were
      immersed in an artificial caries medium (pH 4.5) for 5 days. Each slab was
      sectioned and analysed by quantitative microradiography. RESULTS: The results
      indicate that dentine acquired significantly different amounts of fluoride from
      the three composites. The acid resistance of dentine in contact with the
      composites was also significantly different among the composites and followed the
      same order as for fluoride uptake. CONCLUSIONS: Dentine fluoride uptake and
      artificial caries inhibition were significantly greater with FluorEver followed
      by FluoroCore and Pertac-Hybrid.

PMID- 9175361
TI  - Water uptake of soft lining materials from osmotic solutions.
AB  - OBJECTIVES: The water uptake characteristics of soft lining materials are of
      obvious importance in that they are expected to function in the oral environment.
      Results for Novus (Hygenic Corp., Akron, OH, USA) show a very high uptake from
      distilled water. Despite this high uptake, Novus appears to function
      satisfactorily in the mouth. High water uptake of soft lining materials has been
      attributed to the presence of water soluble impurities that, on immersion, form
      solution droplets; the driving force for the uptake being the osmotic gradient
      between the droplets and the external solution. Uptake should therefore be less
      from ionic solutions. The object of this study was to test the applicability of
      this theory to Novus and two experimental soft lining materials. METHODS: Water
      uptake of two experimental materials and Novus has been determined from distilled
      water and two saline solutions (0.45 and 0.9 M). After 196 days specimens were
      desorbed to constant weight and then subjected to a second sorption cycle.
      RESULTS: Novus had the highest uptake from distilled water at approximately 18%,
      the experimental materials having an uptake approximately 7%. Desorptions were
      all rapid, minimum weight being reached within 1-2 days. Uptakes of the second
      sorptions from water were all higher. Uptake from saline solutions was
      approximately 12% for all materials, uptake from 0.9 M saline being the lowest.
      Second sorption results from solution were similar to the first. CONCLUSION: The
      results obtained support the theory that the high water uptake of elastomeric
      materials is osmotically driven.

PMID- 9175362
TI  - Volume of the internal gap formed under composite restorations in vitro.
AB  - OBJECTIVES: The gap that develops at the interface of dentin composite
      restoration during the polymerization of the resin can be subsequently filled by
      fluid filtrating from the pulp via the dentinal tubules. This in vitro study was
      designed to determine the volume of such a gap, at the occlusal floor of class I
      restoration and as a result of different dentin treatments and restoration
      procedures. METHODS: Fifty-six human third molars had their pulp chambers first
      sealed and connected to a hydraulic apparatus permitting microlitre fluid shift
      recordings. The teeth then received class I cavities of uniform dimensions and
      were sampled into nine groups for three dentin treatments (bonding with a dentin
      bonding agent, lining with a resin modified light-cured glass ionomer, lining
      with a zinc phosphate cement) and three restoration procedures (Bulk placement of
      the composite material, Multilayer, Indirect inlay). Fluid displacements were
      recorded during the filling procedures and stopped 30 min after the completion of
      the restorations. RESULTS: Dentin bonding agent treated cavities consistently
      presented the smallest gap volumes, followed by the GI and the ZnPO4 lined
      specimen. Multilayer and Indirect restoration techniques reduced the formation of
      gaps. CONCLUSIONS: None of the materials or techniques tested assured a gap-free
      interface and more effort should be directed at increasing the adhesive and
      sealing properties of restorative materials to be placed on the dentin.

PMID- 9175363
TI  - Ultimate tensile strength of PDL of molars in rats after 1-hydroxyethylidene-1,1
      bisphosphonate injections.
AB  - OBJECTIVES AND METHODS: Administration during root formation of a bisphosphonate,
      1-hydroxyethylidene-1,1-bisphosphonate (HEBP), at a dose corresponding to 10 mg
      P/kg body weight, has been found to interfere with the formation of acellular
      cementum in rats. The purpose of this study was to measure the force required to
      extract a tooth lacking normal acellular cementum, and to correlate this force
      and the ultimate periodontal strength with the morphology of the periodontal
      tissues at different time intervals after single or multiple injections of HEBP.
      RESULTS: A single injection of HEBP given during root formation inhibited the
      formation of acellular cementum and resulted in a temporary reduction of the
      extraction force and the ultimate tensile strength. Ninety days after the
      injection of HEBP, both parameters were the same as in the controls. The increase
      in extraction force and ultimate tensile strength was associated with the onset
      of occlusal contact of the teeth. The organization of periodontal ligaments was
      improved after the teeth reached the occlusal level. After daily injections of
      HEBP for 3 days, there was a permanent reduction in root length and dento
      alveolar ankylosis developed in the furcation area. CONCLUSION: (1) A single or
      three injections of HEBP changed the formation of acellular cementum to that of
      an atypical hyperplastic cementum which increased the resorption risk at this
      site. (2) The ultimate tensile strength was markedly reduced in teeth lacking
      acellular cementum.

PMID- 9175364
TI  - Physical properties and gap formation of light-cured composites with and without
      'softstart-polymerization'.
AB  - OBJECTIVES: Recently it has been pointed out that light-initiated
      prepolymerization at low intensity followed by a post-light-cure at full
      intensity ('softstart-polymerization') may lead to light-cured composite fillings
      with improved marginal adaptation. The aim of this study was to examine the
      influence of this procedure with different initial cure conditions on physical
      material properties like flexural modulus, flexural strength and Vickers
      microhardness of different composites. Additionally, an in vitro study was
      carried out to investigate the influence of different initial cure conditions on
      the marginal quality of composite restorations in cases of Class V cavities with
      a cemento-enamel junction. METHODS: Physical properties of composite materials
      Tetric (Vivadent, Liechtenstein) and Charisma (Kulzer, Germany) were evaluated.
      Three hundred specimens were made for the flexural tests performed similar to EN
      24049:1993. Microhardness was measured with a Vickers indenter. For the in vitro
      study of Class V composite fillings, cavities of 32 extracted teeth were filled
      with Tetric and analysed by quantitative marginal gap analysis and dye
      penetration test before and after thermocycling. RESULTS: The results indicate
      that initial cure with decreased light intensity followed by final cure with high
      light intensity has no influence on microhardness and increases flexural modulus
      and flexural strength. With the low-level initial cure/high-level final cure
      regime the marginal integrity was significantly better compared with the high
      light intensity curing system. CONCLUSION: Therefore, initial cure with low light
      intensity followed by final cure with high light intensity significantly improves
      the marginal integrity of light-cured composite fillings and also the material
      properties.

PMID- 9175365
TI  - In vitro measurement of cuspal strain and displacement in composite restored
      teeth.
AB  - OBJECTIVES: This study was carried out to measure changes in cuspal strain and
      displacement occurring during placement and polymerization of bonded composite
      restorations in extracted human teeth in vitro. METHODS: Strains were measured
      using electrical resistance strain gauges bonded to the buccal and lingual cusps
      of each specimen and cuspal displacement was recorded with a linear variable
      differential transformer. Mesio-occluso-distal cavities of two types were
      prepared in lower molar teeth. Following enamel acid etching and application of a
      dentine adhesion promoter, specimens were restored incrementally with a light
      curing posterior composite material. RESULTS: It was shown that the shrinkage of
      a composite material during polymerization generated stresses which resulted in
      tensile strains on the tooth surface. Strains of up to 882 microns/m were
      recorded and a maximum cusp displacement of 14 microns was also measured. These
      strains were reduced but not eliminated by preparation and restoration a mesio
      distal slot running the full length and depth of the restoration. Statistical
      analysis revealed significantly higher strains and displacement produced on the
      buccal cusps of teeth that had a reduced cusp width (P < 0.001). CONCLUSIONS: The
      in vitro restoration of posterior teeth with a bonded composite material
      generates polymerization stresses which can be recorded as tensile strains and
      displacements on the tooth surface. Strains measured during composite placement
      were greater when the remaining cusp width was less. A stress relief procedure
      resulted in a decrease in cuspal strain and displacement of approximately 30-40%.

PMID- 9175366
TI  - Effect of dentine depth on the fracture toughness of dentine-composite adhesive
      interfaces.
AB  - OBJECTIVES: The fracture toughness test was recently introduced as a clinically
      relevant method for assessing the fracture resistance of the dentine-composite
      interface. The objective of this study was to evaluate the effect of dentine
      depth on the interfacial fracture toughness test of several dentine-composite
      interfaces using some new proprietary dentine bonding agents. METHODS: Miniature
      short rod fracture toughness specimens containing a chevron-shaped dentine
      composite-bonded interface were prepared for each group (n = 12). Six different
      dentine bonding agents and two dentine depths were the variables assessed at the
      dentine-composite interfaces. After 24 h at 37 degrees C in water, the specimens
      were tested by loading at 0.5 mm/min in the Instron Universal Testing Machine.
      The interfacial KIC results were analysed by ANOVA, unpaired Student's t-tests
      and Fisher's LSD test (P < 0.05). RESULTS: The interfacial KIC results in MN.m
      3/2 (S.D.) on superficial and deep dentine, respectively, were: All-Bond 2, 0.80
      (0.21), 0.44 (0.13); Bond-lt, 0.75 (0.20), 0.38 (0.19); Prime and Bond, 0.56
      (0.11), 0.28 (0.10); Scotchbond Multi-Purpose, 0.45 (0.23), 0.26 (0.15); One-Step
      and OptiBond, insufficient results due to premature specimen failures.
      CONCLUSIONS: The results from this study should contribute to the development of
      the fracture toughness test as a method for assessing the integrity of the
      dentine-composite interface. The interfacial fracture toughness test determined
      significant differences among the different dentine bonding agents and between
      the superficial and deep dentine substrates. The dentine bonding agents showed
      significantly reduced interfacial fracture toughness results when bonding to deep
      versus superficial dentine.

PMID- 9175367
TI  - The protein content of dental rubber dams.
AB  - OBJECTIVES: The purpose of this study was to analyse the protein content of 17
      commonly used rubber dams and to determine if they contained known allergenic
      proteins. METHODS: Proteins were eluted with buffer from 17 brands of
      commercially available rubber dams. The quantity of eluted protein was measured
      and expressed in micrograms in every gram of rubber. The molecular weights of the
      individual proteins eluted were then measured after resolution on sodium dodecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and compared with those of
      known allergens. RESULTS: The rubber dams were shown to contain significant
      amounts of protein (950-5850 micrograms). The subsequent analysis of these
      proteins using SDS-PAGE confirmed that some of these proteins were of the same
      molecular weight as known allergens. CONCLUSIONS: The results of this study
      confirm that all the rubber dams tested contained significant amounts of protein.
      The molecular weights of these proteins correspond with those of known allergens,
      and they could, therefore, be a cause of hypersensitivity reactions to dental
      rubber dams.

PMID- 9175368
TI  - The height of occlusal registration blocks before and after jaw registration.
AB  - OBJECTIVES: To assess the height of occlusal registration blocks made in dental
      laboratories compared with recommended dimensions. To relate these dimensions to
      the height of the blocks after registration of the occlusion. METHODS: All
      occlusal registration blocks received in a complete denture clinic at the Charles
      Clifford Dental Hospital, Sheffield, over a 1-year period were measured in height
      before and after registration of the occlusion. RESULTS: The height of occlusal
      registration blocks as received corresponded to the recommendations in the
      literature. However, after registration, a significant reduction in height was
      seen for both maxillary and mandibular blocks. CONCLUSIONS: Occlusal registration
      blocks produced by laboratories are 34 mm too high, requiring removal of excess
      wax in the surgery.

PMID- 9175369
TI  - Laparoscopic transperitoneal lumbar sympathectomy: a new approach.
AB  - A report of five sympathectomies for the treatment of vasospastic symptoms of
      coldness, rest pain and trophic lesions at the affected feet. Three patients had
      a right-sided sympathectomy done and the other two had left-sided done via
      laparoscopic surgery. This report has advocated original techniques: Under
      general anesthesia, a patient is put into a lateral position with the table
      broken between the ribs and iliac crest. The telescope port is inserted
      horizontally at the edge of the rectus sheath in line with the umbilicus. Two
      secondary ports (5 mm, 10 mm) are inserted under direct vision in the
      midclavicular line. The peritoneal reflection lateral to the colon is incised
      down to the pelvic brim. The use of the lateral position facilitates medial
      displacement of the colon and the kidney by virtue of gravity. The L2, L3, L4
      sympathetic ganglia are then doubly clipped and divided between clips. When such
      a small piece of the sympathetic trunk has been removed, a laparoscopic
      transperitoneal lumbar sympathectomy should be a very reasonable, safe, minimally
      invasive alternative to the traditional operation.

PMID- 9175370
TI  - Linac based radiosurgery (X-knife) for brain metastases.
AB  - Linac based stereotactic radiosurgery by X-knife, technique that permits the
      precise delivery of a high dose of radiation from 6 MV linear accelerator to
      intracranial target(s) while sparing the normal tissue, has been used as an
      alternative treatment for brain metastasis. Five patients with 9 metastatic
      lesions were treated with this technique. The radiation dose was 15-25 Gy with
      the 75-80 per cent isodose line encompassing the enhancing tumor according to the
      tumor volume, site and previous treatment. All metastatic lesions were evaluated
      at 4 weeks after treatment, there were 2 CR, 4 PR and 3 remained unchanged. The
      result showed a very distinct clear radiation effect margin between the target
      and normal tissue. The patient could tolerate the treatment procedure well
      without any complications inherent to the technique. All patients with
      neurological symptoms had a satisfactory recuperation. Radiosurgery with X-knife
      is an effective and safe therapy for brain metastases. It can be applied as a
      primary treatment, as a booster in combination with whole brain irradiation, or
      as treatment for patients with relapse in a previous irradiated area.

PMID- 9175371
TI  - Topical piroxicam and conjunctivitis.
AB  - The study of comparison of the clinical responses of acute hemorrhagic
      conjunctivitis to antibiotic eye drops alone and combined with topical piroxicam
      was analyzed. Seventy-five patients (146 eyes) with viral conjunctivitis were
      randomly assigned to receive topical antibiotic (35 cases) or antibiotic combined
      with piroxicam eye drops (40 cases). The patients were examined under slit lamp
      biomicroscope every other day for the first week, then twice a week until
      recovery. There was no statistically significant difference between groups in
      mean age, sex, bilaterality, history of contact, systemic involvement, mean
      incubation period, mean onset and mean follow-up time. Mean recovery time in the
      piroxicam group (4.9 days) was less than for the control group (P = 0.003).
      Foreign body sensation, pain and tearing in the piroxicam group recovered
      significantly faster than in the control group. Complete recovery of all symptoms
      and signs in piroxicam treated eyes (61%) was significantly more common than with
      antibiotic only (29%) in spite of more drug induced burning. Piroxicam eye drops
      may have beneficial effects for acute hemorrhagic conjunctivitis to relieve
      discomfort, pain, and accelerate recovery.

PMID- 9175372
TI  - Correlation of bone mineral density among various measurement sites.
AB  - Bone mineral density (BMD) of the lumbar spine and hip was studied in 1,047 women
      visiting the menopause clinic, to assess the correlation of BMD among various
      measurement sites. Bone mass measurement was performed utilizing dual energy X
      ray absorptiometer (DEXA), Hologic QDR 2000. The results revealed a significantly
      high correlation of BMD of total hip and spine. (r = 0.7021, P < 0.001)
      Nevertheless, BMD of the spine was mostly correlated with BMD of trochanteric
      site (r = 0.7235, P < 0.001) and least correlated with BMD of intertrochanteric
      region. (r = 0.2426, P < 0.001) In conclusion, BMD of spine and hip is highly
      correlated. However, there was some heterogeneity of correlation in different
      specific measurement sites.

PMID- 9175373
TI  - Climacteric complaints of paramedical personnel.
AB  - This study was conducted from October 1995 to January 1996, to assess the
      prevalence of climacteric complaints of paramedical personnel in Chulalongkorn
      Hospital. Data collection was performed using a standardized questionnaire,
      comprised of population characteristics, items and severity of climacteric
      complaints. All the participants filled up the questionnaire by themself after
      receiving a clear explanation of the meaning of each symptom. Two hundred and
      ninety women aged 40-59 years participated in the study. Their mean age was 47.72
      +/- 4.77 years. Forty six per cent of the study population were classified as
      premenopausal, i.e. having regular vaginal bleeding during the last 12 months, 18
      per cent were perimenopausal, i.e. having irregular vaginal bleeding during the
      last 12 months and 35 per cent were postmenopausal, i.e. having no vaginal
      bleeding during the last 12 months. The mean time since menopause of the last
      group was 4.71 +/- 3.75 years. The results revealed that the prevalence of
      vasomotor symptoms, urogenital symptoms and other symptoms i.e. numbness,
      forgetfulness, etc, were reported at a significantly higher rate in the
      postmenopause than in the perimenopause and premenopause women respectively (P <
      0.05). However, there was no significant difference in the prevalence of
      psychological symptoms among the three groups (P > 0.05). In conclusion, except
      for psychological symptoms, the reported prevalence of climacteric complaints in
      paramedical personnel was associated with menopausal status.

PMID- 9175374
TI  - Prevalence and risk factors for depression in children: an outpatient pediatric
      sample.
AB  - The purpose of this research was to study the prevalence, type, and psychosocial
      stressors associated with depression. The subjects were 81 children who came to
      the outpatient pediatric clinic, Chulalongkorn Hospital. There were 39 boys and
      42 girls with the age range of 9.3-15.3 years. The results of the study were as
      follows. The prevalence of depression was 34.6 per cent. Types of depression were
      depressive symptoms only, 7.4 per cent; adjustment disorder with depressed mood,
      17.3 per cent; dysthymia, 6.2 per cent; and major depression, 3.7 per cent.
      Females had more severe symptoms than males. Of the depressed group, 60.7 per
      cent had previous suicidal behavior compared with 20.6 per cent in the non
      depressed group (p < 0.001). The rates of all psychosocial stressors were higher
      in the depressed group. Those with statistical significance were parental
      psychiatric illness, unstable living condition and history of abuse. Depressed
      children also experienced twice the number of psychosocial stressors compared
      with the non-depressed group (p < 0.01). This study shows that depression is
      prevalent in children with physical illnesses. It is imperative that physicians
      be aware of this problem especially in children who have many psychosocial
      stressors.

PMID- 9175375
TI  - Continuation electroconvulsive therapy in schizophrenia: a pilot study.
AB  - Continuation and maintenance electroconvulsive therapy (ECT-C & ECT-M) has been
      used to control schizophrenic patients for more than 50 years. In spite of this,
      there has been no prospective study made of this treatment. Most of the
      information comprises naturalistic studies or case reports. As a result many
      unanswered questions concerning ECT-C & ECT-M remain, including its therapeutic
      efficacy. This pilot study was prospectively completed on 16 schizophrenic
      patients, suffering acute exacerbations in order to determine the merits of ECT
      C. After acute treatment using only ECT, 12 patients were identified as ECT
      responders and enrolled in this study. No neuroleptic drugs were used. Diazepam
      was the only medication prescribed to control agitation on prn basis. The
      duration of the study was 6 months. Bilateral ECT was used throughout the study,
      after the acute treatment. Global Assessment of Functioning (GAF), Brief
      Psychiatric Rating Scale (BPRS) and the Thai Mental State Exam (TMSE) were used
      to measure the outcome. A total of 8 patients completed the study and 4 dropped
      out. There were no relapses and all measurements progressed satisfactorily. There
      were no serious side effects, in particular no cognitive impairment. This study
      supports the therapeutic efficacy of ECT-C in schizophrenia.

PMID- 9175376
TI  - Relationship between dyspnea, peak expiratory flow rate and wheeze in obstructive
      lung disease.
AB  - The relationship between dyspnea and airway obstruction is complex, and it is
      unclear to what extent measures of each correlate in patients with obstructive
      lung disease (OLD). Thus, the correlation between subjective assessment of
      dyspnea (dyspnea score using modified Borg scale) and objective assessment of
      dyspnea (peak expiratory flow rate using Mini Wright Peak Flow Meter and wheeze
      score using stethoscope) before and after bronchodilator (1 mg of turbutaline
      sulphate) were studied in 115 patients (62 males, 53 females) with OLD attending
      the chest clinic of Royal Irrigation Hospital, Nonthaburi, Thailand. The mean age
      of these patients was 47.4 +/- 16.4 years. Good correlations were found (r = 0.37
      to 0.52; p < 0.001) but dyspnea scores were better correlated with wheeze scores
      than peak expiratory flow rates. The change in dyspnea scores after
      bronchodilator also correlated with the change in peak expiratory flow rates and
      the change in wheeze scores (r = 0.22; p < 0.02 and r = 0.28; p < 0.005
      respectively). Analyzing a subgroup of 48 dyspneic patients (prebronchodilator
      dyspnea score of 2 or more) revealed the following response groups: those with
      either a bronchodilator or dyspnea response alone, both together, or neither.
      Twenty-three patients (47.92 per cent) responded both subjectively and
      objectively. One (2.08 per cent) had a bronchodilator response only. Twenty
      (41.66 per cent) had a dyspnea response only, while four (8.33 per cent) had
      neither measurable response. The present study suggests that the assessment of
      dyspnea by using dyspnea score is vital and may be specially helpful in a
      situation where the objective assessment cannot be performed. In some individuals
      the subjective assessment of response to bronchodilator may be at least as
      valuable as objective data.

PMID- 9175377
TI  - Coronary intervention 1996.
AB  - Interventional cardiology, in particular coronary angioplasty has progressed over
      the recent years. It is one of the three methods in treating coronary artery
      disease. The authors reviewed the advancement of this technique.

PMID- 9175378
TI  - Exchange transfusion therapy in severe complicated malaria.
AB  - Two groups of sixteen cases of severe complicated falciparum malaria on two
      different regimens of treatment were retrospectively studied. The first group
      including 12 patients, were treated by anti malarial drugs alone. The second
      group including 4 patients, were treated by exchange transfusion. Multisystemic
      complications were observed in both groups. It was observed that in complicated
      Acute Respiratory Distress Syndrome (ARDS), renal and hyperparasitemia were > 30
      per cent. The result of the exchange transfusion group was superior to the non
      exchange group. Exchange transfusion is therefore recommended in the treatment of
      malarial patients who present with parasitemia > 30 per cent and severe
      multisystemic complications particularly those who have severe acute renal
      failure or have lung complications. The amount of blood used for each exchange
      transfusion should be at least 10-14 units for rapid removal of parasites and
      toxic metabolites from the circulation.

PMID- 9175379
TI  - Progressive cerebral occlusive disease after hypothalamic astrocytoma radiation
      therapy.
AB  - An 18 year-old woman received radiation therapy for hypothalamic astrocytoma at
      the age of 11 years. She developed progressive cerebral occlusive vascular
      disease with moyamoya vessels formation in both carotid systems. Apart from
      diabetes mellitus, she had no other risk factors for occlusive cerebrovascular
      disease. The site of occlusion was confined to the field of radiation and the
      development of moyamoya vessels strongly suggestive of a radiation-induced cause.
      Radiation therapy around the sella and parasellar region appears to be the most
      common risk factor for this vasculopathy. Progressive irradiation-induced
      cerebral vasculopathy is due to accelerated atherosclerosis.

PMID- 9175380
TI  - The prevalence of inadequate vitamin A nutriture in preschool children of north
      and northeast Thailand.
AB  - Previous surveys have suggested that preschool children in the North and
      Northeast of Thailand are at risk of inadequate vitamin A nutriture. Therefore,
      vitamin A status was assessed in 996 children aged 2-6 years in the North and
      Northeast Thailand during the dry (Feb.-April) and rainy (Sept.-Nov.) seasons.
      Approximately 1 per cent of samples during both periods exhibited serum retinol
      concentrations below 10 mcg/dl with means (+/-SD) concentration of 29 +/- 9.8
      mcg/dl in the dry season and 37 +/- 15.4 mcg/dl in the rainy season. About one
      fifth of the studied children showed abnormal CIC and depleted liver stores (RDR
      > 20%). High risk areas were ranked and corresponded well by these 2 indicators.
      Therefore, it is concluded that the magnitude of the problem estimated by RDR and
      CIC are a more precise measurement of marginal vitamin A status than serum
      vitamin A level alone and about one-fifth of preschool children in the North and
      Northeast regions of Thailand experience subclinical vitamin A deficiency.

PMID- 9175382
TI  - Osteosarcoma: a study of 130 cases.
AB  - Multidisciplinary treatment of osteosarcoma in the Faculty of Medicine
      Ramathibodi Hospital, Mahidol University, using preoperative intraarterial and
      postoperative chemotherapy, with or without local irradiation, combined with
      surgery and prophylactic lung irradiation provided an excellent 5 years' survival
      of 55 per cent, the same rate as the 9 years' survival. The survival was stable
      after 4.4 years. The patients with local irradiation had more tumor destruction
      apparent on the surgical specimen. The administration of prophylactic whole lung
      irradiation provided an outcome without any undesirable complication. Sixteen per
      cent of the cases with PLI developed lung metastasis compared to 48 per cent
      without PLI. The most important prognostic factor was low level of serum lactic
      acid dehydrogenase. The unanswered question is what is the optimal treatment for
      osteosarcoma?

PMID- 9175381
TI  - Serum estradiol and gonadotropins level in postmenopausal women with or without
      hormone replacement.
AB  - Serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol
      (E2) was measured in 49 menopausal women, to assess the changing serum level in
      women with or without hormone replacement. Women in the study group (N = 25)
      received estrogen with or without progestin. The control group (N = 24) did not
      receive any hormone regimen. Serum hormone measurement was done at 0, 6 and 12
      month, using time-resolved fluoroimmunoassay method. The results revealed no
      significant change of FSH, LH and E2 at 0, 6 and 12 month in the control group.
      (FSH at 0, 6, 12 month: 55.14 +/- 22.82, 63.90 +/- 24.54, 72.81 +/- 29.58 IU/L, P
      = 0.09; LH at 0, 6, 12 month: 35.54 +/- 19.86, 33.02 +/- 16.30, 32.33 +/- 17.37
      IU/L, P = 0.83; E2 at 0, 6, 12 month: 49.28 +/- 48.54, 37.29 +/- 39.93, 25.63 +/-
      23.58 pmol/L, P = 0.17). However, in the study group, FSH and LH significantly
      decreased but E2 significantly increased at 6 and 12 months. (FSH at 0, 6, 12
      month: 59.33 +/- 22.30, 27.23 +/- 16.31, 29.74 +/- 19.45 IU/L, P < 0.05; LH at 0,
      6, 12 months: 41.4 +/- 17.02, 19.62 +/- 13.66, 15.65 +/- 8.77 IU/L, P < 0.05; E2
      at 0, 6, 12 months: 47.33 +/- 41.25, 280.94 +/- 174.11, 270.70 +/- 198.65 pmol/L,
      P < 0.05). In conclusion, hormone replacement decreased serum gonadotrophin,
      though not reaching the premenopausal level. However, serum E2 value was
      significantly increased close to the level in the follicular phase of normal
      menstrual cycle.

PMID- 9175383
TI  - Vascular injuries of the upper arm.
AB  - Twenty eight patients who had subclavian, axillary, and brachial artery injuries
      were studied. Sixteen (57%) sustained blunt trauma and 12 (43%) sustained
      penetrating trauma. Motor cycle accidents were the most common cause of injuries
      (43%). Twenty patients (71.4%) were transferred from other hospitals. Nine
      patients (32%) were in shock on arrival. All patients had radial pulse
      abnormalities (3 decreased, 25 absent) of the affected limbs. Eighteen patients
      (64%) had associated injuries to other parts of the body. Eighteen patients (64%)
      also had associated nerve injuries, 7 of them had complete brachial plexus
      injuries from motor cycle accidents. Twelve patients (43%) had preoperative
      angiography. Twelve patients (43%) had brachial, 10 (35.7%) had axillary, 2 (7%)
      had axillary-subclavian, and 4 (14%) had subclavian artery injuries. Eight
      patients (28.6%) had concomitant venous injuries. Resection of the injured artery
      and reversed saphenous vein graft were performed in 23 patients (82%). The
      remaining had resection and end to end anastomosis in 3 patients (10.7%), lateral
      repair in 2 patients (7%), and ligation in 1 patient (3.6%). Concomitant venous
      repairs were performed in 5 patients. Fasciotomies were performed in 2 patients
      (7%). Excellent results of vascular repairs were obtained in all patients. Long
      term disability occurred in patients who had associated nerve injuries. Avulsion
      injury of the brachial plexus usually resulted in severe impairment of limb
      function.

PMID- 9175384
TI  - APACHE II in a postoperative intensive care unit in Thailand.
AB  - In order to evaluate the effectiveness of an intensive care unit (ICU), the case
      mix has to be considered. This was a cohort study. By using Acute Physiology and
      Chronic Health Evaluation scores (APACHE II score), we evaluated the case-mix and
      mortality rate of 282 patients who were treated in our postoperative ICU. The
      overall mortality rate was 10.6 per cent. Higher Acute physiology scores and
      emergency surgery in the presence of chronic health status were related to higher
      mortality, but age was not. However, the original APACHE II model could not
      precisely predict the mortality of Thai patients. We used stepwise logistic
      regression to determine the predictors of death and found the prediction model to
      be -7.24 + 0.37 (APACHE II score) + 1.46 (postemergency surgery). The actual
      mortality for patients with APACHE II score > 15 in our ICU was higher than that
      predicted by the original APACHE II model. The causes of this difference might be
      difference in methodology, characteristics of ICU and the quality of care.

PMID- 9175385
TI  - Study on the management of diarrhea in young children at community level in
      Thailand.
AB  - An evaluating study was carried out among 15,466 children from households
      randomized from 30 clusters from twelve provinces of twelve regions of Thailand.
      Results of this study revealed 5.13 per cent of incidence-rate of diarrhea among
      young children aged under five years with an average of annual prevalence of 1.3
      per child. The overall mortality-rate and diarrhea associated death were 51.7 per
      100,000 and 6.5 per 100,000 respectively. The utilization of ORS was 25.6 per
      cent while the using-rate of sugar salt solution (SSS) and the use of recommended
      home fluids were 2.8 and 33.8 per cent respectively. As for treatment, the
      intravenous therapy was 6.2 per cent and the use of different types of drugs
      varied from 18.0 to 21.3 per cent. Only 23.7 per cent of parents could correctly
      prepare the ORS. The authors have made recommendations for the strengthening of
      community health education aiming at better promotion of ORS and other home care
      practices for diarrhea as important measures for lowering mortality together with
      relating preventive interventions.

PMID- 9175386
TI  - Alprazolam and standard antidepressants in the treatment of depression: a meta
      analysis of the antidepressant effect.
AB  - Alprazolam differs from other benzodiazepines by the incorporation of a triazolo
      ring in the basic chemical structure. Several lines of evidence have supported
      that alprazolam and standard antidepressants have some similar actions, such as
      beta-adrenergic receptor down-regulation, antipanic effect. Because of the
      difference in opinions pertaining to the antidepressant effect of alprazolam,
      this issue could not reach a firm conclusion. In the present analysis, we carried
      out a meta-analysis of 11 random controlled studies that compared the
      antidepressant effect of alprazolam and standard antidepressants in depressed
      patients. The results showed that the weighted mean effect size d (dw) is equal
      to 0.06. In conclusion, the antidepressant effect of alprazolam is comparable to
      that of low-dose tricyclic antidepressants. Very few studies have investigated
      severely depressed patients. Also, in long-term administration, the lack of a
      long-term treatment study makes the issue of alprazolam's benefits and
      disadvantages still undetermined.

PMID- 9175387
TI  - Comparison of intracervical and intravaginal misoprostol for cervical ripening
      and labour induction in patients with an unfavourable cervix.
AB  - OBJECTIVE: To compare the efficacy of intracervical versus intravaginal
      misoprostol for cervical ripening and labour induction at term in patients with
      an unfavourable cervix. METHOD: A total of 100 pregnant women with indications
      for induction of labour and unfavourable cervix (Bishop score < or = 4) were
      randomly assigned to receive either 100 ug misoprostol administered
      intracervically (50 cases) or intravaginally (50 cases). RESULTS: No significant
      differences were noted between intracervical and intravaginal misoprostol in
      terms of Bishop score change, (score 7.2 vs score 7.5), interval from gel
      insertion to vaginal delivery (17.0 hours vs 16.4 hours), meperidine as analgesic
      requirement (80% vs 76%), route of delivery and perinatal outcome. Uterine
      tachysystole occurred in 24 per cent and 32 per cent in the intracervical and
      intravaginal groups respectively which did not significantly differ, however, all
      could be rapidly resolved by terbutaline injection. No evidence of fetal distress
      was noted in these events. Spillage of gel out of the cervix was observed in 70
      per cent of patients receiving intracervical misoprostol. Fever was observed in
      one patient of each group. No other serious side effects were found in both
      groups. One patient in the intravaginal group had postpartum hemorrhage due to
      delayed placental separation and uterine atony. CONCLUSION: The two routes of
      misoprostol gel application appear to be safe and equally effective in ripening
      cervix and inducing labour, however, the intravaginal application is more
      convenient to administer practically compared with the intracervical.

PMID- 9175388
TI  - Castleman's disease: a clinicopathologic study of 12 cases.
AB  - Castleman's disease observed in 12 Thai patients was investigated. The male to
      female ratio was 1:3. Peak prevalence was in the third and fourth decades. It is
      suggested that the disease in Orientals tends to have extrathoracic mass more
      often than in Caucasians. Solitary non-tender slow growing mass was the most
      common symptom. Generalized lymphadenopathy in association with cutaneous
      plasmocytoma was noted in one example while asymptmatic pelvic lesion in a
      patient was discovered incidentally. Histologically, the hyaline-vascular type
      was found in 8 instances, the remainders were plasma-cell type. Surgery was
      effective for localized lesions while systemic form could benefit from
      chemotherapy.

PMID- 9175389
TI  - Antitriiodothyronine antibody in patient with Hashimoto's thyroiditis.
AB  - We described a 44-year-old female patient with a history of goiter for 2 months.
      Physical examination revealed a diffusely enlarged thyroid gland weighing 40 g
      firm to hard in consistency. She was clinically euthyroid and had neither
      ophthalmopathy nor dermopathy. Serum thyroid hormone levels revealed total T4
      (RIA) of 4.8 micrograms/dL (normal, 4-11 micrograms/dL), total T3 (RIA) of above
      600 ng/dL (70-175 ng/dL), and TSH (IRMA) of 54 mU/L (0.3-6 mU/L).
      Antithyroglobulin and antiperoxidase antibody titers were 1:5,120 and 1:409,260,
      respectively. Because of the discrepancy between the patient's clinical status
      and laboratory values, assay for thyroid hormone autoantibodies (THAA) was done
      and subsequently demonstrated antitriiodothyronine antibody with percentage of
      precipitation by polyethylene of 98.4 per cent (normal range, 3.06 +/- 8.58%). In
      conclusion, THAA should be suspected in patients whose clinical status is
      incoherent with the thyroid function test.

PMID- 9175390
TI  - Squamous cell carcinoma of head and neck.
AB  - Head and neck cancers are a major heath problem and common malignancies in
      Thailand. Up to 80 per cent of cases are caused by smoking and alcohol
      consumption. Epithelial mucosa of the aerodigestive tract exposed to carcinogens
      results in cellular mutations at different areas by a process called field
      cancerization and causes multistep carcinogenesis. Over 90 per cent of cases are
      squamous cell carcinoma. Prognostic factors depend on the patients, diseases and
      treatment. Currently, several molecular pathogenesis have been discovered such as
      abnormalities of c-myc, c-ras, c-erbB-1, bcl, int-2, hst1 oncogenes, p53 and p16
      tumor suppressor genes. Common chromosomal abnormalities are 3p, 9p, 11q, 13q,
      17p. Diagnosis requires symptoms and signs, radioimaging, and pathology. Stage I
      and II can be treated by surgery or radiotherapy. However, stage II requires and
      combination of surgery and radiotherapy, and studies of chemotherapy and local
      treatment to increase therapeutic efficacy by several approaches such as
      combination chemotherapy, new drugs, and biologic therapy.

PMID- 9175391
TI  - Hepatic peripheral T-cell lymphoma: a spectrum of liver pathology and clinical
      correlation.
AB  - Thirty-two patients with fever of unknown origin, weight loss, anemia, elevated
      serum levels of alkaline phosphatase and/or lactate dehydrogenase were evaluated.
      Histopathologic findings of the liver showed T-cell infiltration in the hepatic
      sinusoids and portal tracts. The cellular morphology varied from mature
      lymphocyte to malignant lymphoid cells. We divided the cases into four groups on
      the basis of cellular atypia. Group A and group B showed mature lymphoid cell
      infiltration, however, only group B had multiple large areas of hepatocellular
      necrosis. Group C showed atypical lymphoid cell infiltration. In group D,
      definite malignant lymphoid cell infiltrates were demonstrated. Groups B, C, and
      D patients had a very poor prognosis. All of them died despite chemotherapy.
      Group A patients had a better prognosis. Those who had chemotherapy achieved a
      complete remission. Progression to a higher group occurred in two of six patients
      with group B lesions and one of seven patients with group C lesions. The EBV-RNA
      genomes were found increasingly in the higher groups. This study supports the
      concept that these groups of disease represent a spectrum of peripheral T-cell
      proliferations.

PMID- 9175392
TI  - Efficacy of using basal plasma adrenocorticotropic hormone-radioimmunoassay (ACTH
      RIA) level in the identification of the cause of Cushing's syndrome.
AB  - Basal (8.00 a.m.) plasma ACTH-radioimmunoassay (ACTH-RIA) levels were studied in
      32 cases of endogenous Cushing's syndrome (17 Cushing's disease, 13
      adrenocortical tumors, and 2 ectopic ACTH syndrome) and 11 normal volunteers.
      There were overlaps in the ranges of plasma ACTH-RIA levels among patients with
      Cushing's disease, adrenocortical tumors, and normal volunteers but not ectopic
      ACTH syndrome. By using different plasma ACTH-RIA levels as cut-off points in
      differentiating ACTH-dependent from ACTH-independent Cushing's syndrome, the
      level of 30 pg/ml had the highest diagnostic efficacy with a 94.7 per cent
      sensitivity, a 84.6 per cent specificity and a 90.6 per cent diagnostic accuracy.

PMID- 9175393
TI  - Termination of second-trimester pregnancy with intracervicovaginal misoprostol.
AB  - To evaluate the efficacy and side effects of intracervicovaginal misoprostol in
      termination of second-trimester pregnancy in women with live fetuses. A total of
      50 pregnant women between 14 and 27 week's gestation undergoing termination of
      pregnancy for medical, obstetrical and genetic reasons were recruited to receive
      200 ug misoprostol gel administered intracervicovaginally every 12 hours. The
      rates of successful abortions within 24 hours and 48 hours were 54 per cent and
      92 per cent respectively. The mean time from induction to abortion was 27.5
      hours. The rate of complete abortion, defined as the passage of the fetus and
      placenta without operative assistance was 80 per cent. Side effects were fever
      (8%), nausea and vomiting (6%) and diarrhea (2%). Thirty one patients (62%)
      required meperidine as analgesia. Two patients (4%) had postpartum hemorrhage.
      Intracervicovaginal misoprostol is an effective, cheap, safe and relatively
      convenient method for termination of second-trimester pregnancy with a live
      fetus.

PMID- 9175394
TI  - The size of the vertebral canal and the significance of epidural fat in lumbar
      spinal stenosis.
AB  - Measurements of mid sagittal diameter (MSD) and interpedicular diameter (IPD) in
      patients operated on for central lumbar spinal stenosis were compared to the
      control group. Both groups can be matched in terms of gender and age. We found
      that in the stenotic patients the MSD and the IPD were smaller than in the
      control group, all of the measurements except the IPD in male stenotic patients
      was statistically different. Sagittal and axial MR images of the stenotic
      patients were used to evaluate the status of the posterior epidural fat which was
      graded as normal, small, very small and absent. All the patients were surgically
      treated for lumbar stenosis, imaging studies and intraoperative finding were
      correlated. Reduction or absence of the posterior epidural fat (PEF) by the
      imaging studies were found to be related to the intraoperative findings and the
      duration of symptoms. PEF may be used as an intraoperative indicator for optimal
      surgical decompression.

PMID- 9175395
TI  - Symptoms and problems of menopausal women in Klong Toey slum.
AB  - This study was conducted to assess the symptoms and problems of postmenopausal
      Thai women in Klong Toey slum. The interview was randomly performed according to
      the home number by well-trained social workers and a standardized questionnaire
      was used. One hundred and nineteen postmenopausal women were eligible for the
      study. The women were of low socioeconomic and educational background. Their mean
      age was 58.9 +/- 6.9 years. The mean time since menopause was 7 years. The
      prevalence of the climacteric symptoms was as follows: vasomotor symptoms 72.3
      per cent, urological symptoms 80.7 per cent, genital symptoms 87.4 per cent and
      psychological symptoms 98.3 per cent. However, the prevalence of severe
      vasomotor, urological, genital and psychological symptoms which these women
      recognized as problems was 29.4 per cent, 19.3 per cent, 15.1 per cent and 75.6
      per cent, respectively. In conclusion, the prevalence of climacteric symptoms of
      postmenopausal women in Klong Toey slum were high but the symptoms which these
      women recognized as problems were low. These women probably perceived these
      symptoms as a natural change of life.

PMID- 9175397
TI  - Bimanual uterine compression as a major technique in controlling severe
      postpartum hemorrhage from uterine atony.
AB  - A 27-year old woman, primigravida, 33 weeks' gestation, presented with complaints
      of labor pain and absent fetal movement. A dead fetus in utero, abruptio
      placentae, and labor pain were diagnosed. Severe postpartum hemorrhage from
      uterine atony and disseminated intravascular cogulopathy was noted after
      spontaneous delivery of the baby and placenta. Bimanual uterine compression for
      40 minutes was performed as a major procedure accompanied by uterotonic drugs,
      correction of hypovolemic shock and coagulopathy by crytalloid, blood, fresh
      frozen plasma. The patient had no complications when seen at 6 weeks' postpartum
      follow-up.

PMID- 9175396
TI  - Randomized controlled trial of dexamethasone in infectious croup.
AB  - Infectious croup is a common and an important cause of upper airway obstruction
      in young children. Despite its frequency and potentially serious nature, there is
      still no definite conclusion regarding the beneficial effect of corticosteroid. A
      randomized controlled study on the effects of dexamethasone in infectious croup
      was conducted at the Department of Pediatrics, Ramathibodi Hospital between
      January 1985 and September 1986. Thirty-two patients, 2-37 months old, were
      included in this study. Fourteen patients received dexamethasone (0.5 mg/kg/dose
      daily for 3 days) and eighteen patients were the control group. The dexamethasone
      group had significantly lower croup scores at 48 hour (p < 0.05), shorter
      hospital course (p < 0.005) and lower incidence of endotracheal intubation (p <
      0.05) than the control group. Five patients in the control group required
      endotracheal intubation. Complications included four episodes of pneumonia, one
      episode of sepsis, and one bacterial tracheitis. Pneumonia and sepsis occurred
      only in the control group. We concluded that dexamethasone therapy decrease the
      severity of infectious croup and the risk of complications.

PMID- 9175398
TI  - Bullous pemphigoid in an infant: a case report and literature review.
AB  - Bullous pemphigoid is an autoimmune bullous disease that is rare in children and
      infants. It seems indistinguishable from the disease in adults although mucous
      membrane, palms and soles involvement appear more commonly in childhood bullous
      pemphigoid. There is no association with malignancy. The most reliable diagnostic
      criterias are the linear deposition of IgG and C3 along the basement membrane
      zone and the presence of circulating IgG antibasement membrane zone antibodies.
      The literature of bullous pemphigoid is reviewed and a case of a 7-month-old girl
      with typical clinical manifestations and immunofluorescence studies is reported.
      She responded very well to a high dose of systemic corticosteroid. The disease
      can be spontaneously resolved and the prognosis for children is good in most
      cases.

PMID- 9175399
TI  - Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity,
      hypertension, dyslipidaemia and atherosclerosis.
AB  - Insulin resistance syndrome (IRS) has the potential to explain a large group of
      common metabolic and cardiovascular disorders [e.g., obesity, non-insulin
      dependent diabetes mellitus (NIDDM), hypertension, hyperlipidaemia,
      hypercoagulability] which are all in themselves cardiovascular risk factors. This
      contribution firstly reviews the convincing evidence from glucose-clamp studies
      that all of these conditions are characterised by the presence of combined
      insulin resistance and hyperinsulinaemia, and secondly examines the relationships
      of the components of this syndrome to coronary artery disease and to the rational
      choice of antihypertensive therapy.

PMID- 9175400
TI  - Osteoporosis: a view into the next century.
AB  - Osteoporosis is a systemic disease in which fractures in later life result from
      gradual deterioration of bone mass and architecture. It will become an
      increasingly serious problem world-wide as the population ages and as a result of
      a secular trend that is not well understood. A review of information on the
      geographical variation of osteoporosis is followed by a consideration of the
      possible effects of calcium, smoking and exercise. The problem of osteoporosis
      will be very difficult to tackle, but the best preventive approach is probably to
      develop a screening strategy for women well after the menopause-perhaps at 65
      years-and to target interventions to those at highest risk.

PMID- 9175401
TI  - The internist and the vessel wall.
AB  - The essential problem of the vicious circle leading to end-stage cardiovascular
      disease is atherosclerosis. This paper focuses on the functional changes centred
      on the endothelium that accompany the development of atherosclerosis, examining
      in particular pathological alterations in the L-arginine/nitric oxide (NO)
      pathway. Changes in the NO system are associated with altered platelet and
      monocyte interactions with the vessel wall, abnormal vasoconstriction and altered
      vascular structure. Diabetes, hyperglycaemia, hypertension and
      hypercholesterolaemia are all involved in this process. Endothelin is a
      vasoconstrictor peptide produced by endothelial cells which is upregulated under
      these conditions. Normalising endothelial function could involve platelet
      inhibition, lipid-lowering agents to prevent foam cell formation and decrease the
      lipid load of the blood vessel wall, and agents to interfere with some of the
      mechanisms involved in vasoconstriction, proliferation and migration, including
      ACE-inhibitors and angiotensin receptor antagonists, and possibly new tools such
      as endothelin receptor antagonists.

PMID- 9175402
TI  - Cancer and genes: how will molecular biology reshape our clinical practice?
AB  - Cancers develop through a succession of stages marked by the accumulation of
      genetic events within the cell. The rate of occurrence of these events is
      influenced by the genetic make-up of the individual (e.g., differences in the
      metabolism of carcinogens, and in the capacity for DNA repair). Knowledge of
      these events will help define precise targets for early diagnosis. Molecular
      profiles of cancers will predict prognosis and guide the selection of appropriate
      therapy. Genetic differences between cancers and normal cells may at last be
      exploited to make cancer treatment truly selective. An example in clinical trials
      is the 'smart virus' that replicates in and destroys only cancer cells because of
      their defective p53 function. An understanding of the genetic background of
      individuals should allow those at particular risk to be recognised and to develop
      prevention programmes involving targeted screening or the avoidance of
      predisposing environmental factors. Here, however, human behaviour and the
      efficacy of early detection methods are likely to be limiting factors, as is
      already clear from experience with tobacco smoking and with genes for breast
      cancer and ovarian cancer.

PMID- 9175403
TI  - Emerging infections and newly-recognised pathogens.
AB  - Clinicians and microbiologists have for many years relied on growth and
      characterisation of micro-organisms in the laboratory as the major method for
      their detection and identification, but reliance upon microbial growth in the
      laboratory has probably significantly limited our ability to recognise important
      pathogenic micro-organisms. The traditional methods are often slow, non-specific
      and insensitive, and sometimes discriminate poorly among microbial species and
      strains. It is now known that the evolutionary ancestry and interrelationships of
      all living organisms can be reliably inferred from sequences in their genetic
      material. Highly conserved sequences characterise broad phylogenetic groups and
      variable sequences allow specific identification. Sequence-based methods combined
      with DNA amplification methods, such as the polymerase chain reaction (PCR), have
      led to powerful molecular identification techniques such as consensus nucleic
      acid amplification and representational difference analysis. These methods allow
      one to detect and isolate informative gene sequences from occult microbial
      pathogens in human tissues. Sequence-based methods are often quicker, more
      sensitive and more specific than traditional methods not only in detecting known
      microbial pathogens, but also in identifying previously-uncharacterised micro
      organisms. Widespread, organised use of these methods will reveal new emerging
      microbial pathogens, implicate microbes in the aetiology of poorly-understood
      chronic inflammatory diseases and significantly expand our understanding of
      microbial diversity.

PMID- 9175404
TI  - Tomorrow's world: atherosclerosis in the year 2000.
AB  - Atherosclerosis is an increasing problem, largely due to lifestyle changes. Lipid
      accumulates in artery walls throughout life, and infiltration into the subintimal
      space of cholesterol and cholesterol esters and of inflammatory cells can lead to
      narrowing, clotting, thrombosis and death. Lipid-lowering agents, particularly
      statins [(3-hydroxy-3-methylglutarate coenzyme A (HMG-CoA) reductase inhibitors]
      represent one important approach to treatment. They work by blocking the
      conversion of 3-hydroxy-3-methylglutarate into mevalonate, a precursor of
      cholesterol. The West Of Scotland Coronary Prevention Study (WOSCOPS) was a large
      prospective randomised study comparing the effects of pravastatin versus that of
      placebo in 6595 middle-aged men. In the pravastatin group the rate of fatal or
      non-fatal myocardial infarction was reduced by one-third over 5 years, the rate
      of cardiovascular deaths by one-third, and overall deaths by 22% relative to the
      placebo group. Implications of the results are considered and the results of the
      US-CARE study are compared. Discussion of relative and absolute risk, and
      continuous and discrete risk factors leads to the formulation of rational
      cost/beneficial strategies for decreasing cardiovascular risk by targeting high
      risk individuals with lipid-lowering drugs.

PMID- 9175405
TI  - Gastro-entero-hepatology in the next millennium.
AB  - The scope of gastroenterology and hepatology now and its development into the
      next century are great and expanding. Only some of the many exciting improvements
      which are expected during the next few years can be discussed here. Progress in
      the microbial aetiology and novel targeted treatments for inflammatory bowel
      disease (IBD) will be paralleled by better understanding of functional upper and
      lower gut disorders, their neural control and neuropharmacological treatment.
      Technical developments in the pipeline include improvements in endoscopic and
      endosonographic equipment and techniques, including MR- or CT-based 'virtual
      colonoscopy' to obviate many invasive diagnostic colonoscopies, and the
      remarkable self-propelled endoscope, which will worm its way to regions of
      interest in the bowel. In hepatology, transplantation, and vaccination for
      hepatitides will increase, and improved treatment of acute liver failure may
      involve bioreactors or cryopreserved human hepatocytes. Gastrointestinal oncology
      will progress through more extensive surgery, gene therapy and techniques such as
      mucosal resection. A target force of about 150 trained
      gastroenterologist/hepatologists will be needed in the Netherlands--one for every
      100,000 of the population.

PMID- 9175406
TI  - [Evaluation of environmental stimulation and its relation to physical
      deterioration in the elderly after 3 years--a health-social longitudinal study].
AB  - A comprehensive longitudinal study was started in 1991 and has been continuing
      every year to develop an evaluation of environmental stimulation (EES). The
      subjects were all the 60 years or above who lived in a farming community near
      major urban centers in Japan (n = 693). The contents of the interview were about
      the interaction between the individual and the environment, health status and
      life style, their feeling about themselves, and social activities. The results
      were as follows; 1) Environmental stimulation was divided into 5 subscales by
      factor analysis. i.e.: a) Interactive stimulation through family members and
      other people, b) Material stimulation, c) Social interactive stimulation, d)
      Availability of physical environment, e) Promoting self reliance and interaction.
      The cumulative prevalence rate for these factors was 54.2% and Cronbach alpha was
      0.78, 2) Lack of environmental stimulation was significantly correlated to
      physical deterioration over the 3 years duration of the study. Further research
      is needed on this cohort to develop a more effective scale of environmental
      stimulation which can predict precisely the physical deterioration related to
      socio-psychological factors.

PMID- 9175407
TI  - [Application of tuberculosis medical examination radiographs to scoliosis
      screening in high schools].
AB  - The purpose of this study was to assess the utilization of tuberculosis
      examination radiographs for scoliosis screening in high schools, for early
      diagnosis and early treatment of adolescent idiopathic scoliosis in the health
      management of students. We examined 2,068 first year high school students (1,058
      males and 1,010 females) in Wakayama Prefecture, who had chest X-ray photographs
      taken between 1994 to 1996, and 24 cases (3 males and 21 females) were identified
      with scoliosis of more than 10 degrees Cobb angle. Fifteen of the cases received
      further examinations in the hospital, and were diagnosed with definite adolescent
      idiopathic scoliosis, while 6 cases who did not receive hospital examinations had
      their abnormality of the spine noted in past periodic health examinations. In the
      remaining 3 students scoliosis could not be confirmed. The correlation
      coefficient between the Cobb angle measured in the tuberculosis examination
      radiographs and in the total spinal radiographs taken by the hospital was 0.815
      (p < 0.001). These results suggest that the tuberculosis examination radiographs
      may be useful for scoliosis screening in high schools.

PMID- 9175408
TI  - [School-based intervention trial for cardiovascular health].
AB  - The effectiveness of a school-based intervention trial for the primary prevention
      of cardiovascular disease was studied by measuring cardiovascular risk factors in
      701 children with intervention and 663 children without intervention. Outcomes
      were assessed using preintervention measures at 10 years old (fall 1991) and
      follow-up measures at 13 years old (fall 1994). In girls with intervention, HDL
      cholesterol level was significantly higher and atherogenic index was
      significantly lower than that in girls without intervention. In obese girls with
      intervention, frequency of reduced obesity index was significantly higher than
      that in obese girls without intervention. In boys, however, body size and
      cholesterol measures did not differ significantly between intervention groups and
      nonintervention groups. These results indicate that school-based intervention for
      cardiovascular health can produce a reduction in risk factors for atherosclerosis
      in girls over a period of 3 school years.

PMID- 9175409
TI  - [Response rates and non-response bias in a health-related mailed survey].
AB  - A health-related mailed survey was conducted to investigate the effect of follow
      up mailings to response rates. In addition, the answer distributions among early
      and late respondents were compared to check non-response bias. Approximately
      3,000 persons aged 40-64 were randomized into two groups; a questionnaire with
      four pages (twenty-two questions) was assigned to the first group, and a
      questionnaire with eight pages (thirty-five questions) to the second group. Both
      questionnaires contained questions of current health status, health-related
      practice, smoking status, etc. Follow-up mailings were sent twice to non
      respondents. Response rates were increased from 38% to 62% by the first follow-up
      mail, and to 71% by the second follow-up mail. Although the length of the
      questionnaire did not affect response rates, response rates among the older
      subjects was higher than the younger subjects. Positive response to current
      smoking status was 10% lower among early respondents than late respondents,
      collected after the second follow-up mailing, and response to regular
      participation in physical/medical checkup was 15% higher among early respondents,
      whereas there were few differences for answers to other questions. Odds ratios
      between current health status and several health-related questions may not be
      biased by late response. However, increased response rates are needed to prevent
      non-response bias, because there were some differences in responses from follow
      up mailings.

PMID- 9175410
TI  - [Urinary and fecal incontinence in a community-residing elderly population:
      prevalence, correlates and prognosis].
AB  - To estimate the prevalence and risk factors of urinary and fecal incontinence and
      examine its prognosis among a community-residing elderly population, a randomly
      selected sample of 1473 elderly people, aged 65 years and over, living in the
      City of Settsu, Osaka, was investigated in October 1992. Data was obtained from
      1405 for a response rate of 95.4%. The cohort of 1405 was followed for 38 months
      and follow-up was completed for 1325 (94.3%). The main results were as follows:
      1) The prevalence of urinary incontinence of any degree was 9.8% in both sexes,
      and 8.7% men and 6.6% women admitted to some degree of fecal incontinence. 3.4%
      and 2.0% of the elderly were daily incontinent in urine and feces, respectively.
      There was an increasing prevalence of urinary and fecal incontinence with age in
      both sexes. 2) By univariate analyses, age older than 75 years, low activities of
      daily living (ADL), stroke, dementia, no participation in social activities, and
      lack of a perception of having a life worth living were significantly associated
      with both urinary and fecal incontinence. In the multivariate analyses using
      logistic regression, age older than 75 years and low ADL were significantly
      associated with any type of incontinence. Stroke was associated with incontinence
      less than once a day, while dementia was associated with incontinence more than
      once a day. 3) From analysis by Kaplan-Meier method and log-rank test, the
      estimated survival rates were higher among the elderly without incontinence than
      among those with incontinence, and tended to become low with the increased
      frequency of incontinence in both urine and feces. 4) From Cox proportional
      hazards model analysis, less than once daily fecal incontinence and once or more
      fecal and urinary incontinence daily remained as statistically significant
      factors associated with survival, controlling for other factors.

PMID- 9175411
TI  - [Second primary cancers occurring in patients with cancers of the mouth and meso
      hypo pharynx in Japan].
AB  - We evaluated the risk of development of a second primary cancer in 669 patients
      diagnosed with cancers of the mouth and meso-hypo pharynx at Osaka Medical Center
      for Cancer and Cardiovascular Diseases. During 1978-93, 70 of the patients
      developed a second primary cancer, yielding on observed to expected ratio (O/E)
      of 2.92 [95% confidence interval (CI) = 2.27-3.69]. Significant excess risk was
      noted for cancers of mouth and pharynx (O/E = 12.01, 95% CI = 3.87-28.04),
      esophagus (O/E = 25.22, 95% CI = 14.94-39.86), colon (O/E = 3.85, 95% CI = 1.41
      8.39), larynx (O/E = 9.93, 95% CI = 2.00-29.02) and lung (O/E = 2.58, 95% CI =
      1.24-4.75). The risks of esophageal cancer and colon cancer were significantly
      elevated after five years had elapsed from the initial cancer diagnoses. The risk
      of cancers of the oral cavity, pharynx, larynx and esophagus in patients who had
      a history of current smoking without current daily drinking at the initial
      diagnosis was elevated past one year after the initial diagnosis (less than 20
      cigarettes/ day; O/E = 12.50, 95% CI = 0.16-69.55, 20 cigarettes or more; O/E =
      10.00, 95% CI = 1.12-36.10). The risk of cancers of the oral cavity, pharynx,
      larynx and esophagus in patients who had a history of current smoking with
      current daily drinking at the initial diagnosis was around two times higher than
      those who had a history of current smoking without current daily drinking (less
      than 20 cigarettes/day; O/E = 20.00, 95% CI = 2.25-72.21, 20 cigarettes or more;
      O/ E = 19.51, 95% CI = 8.40-38.45).

PMID- 9175412
TI  - [New mental development screening test for use in health examinations of
      infants].
AB  - OBJECTIVE: This study is designed to produce a new mental development screening
      test with predictive validity for future developmental disorders. METHOD: 1. The
      items of mental development screening test were selected provisionally, and the
      results of the items were stored in the 7 months, 10 months, 1 year, 1 year and 6
      months of health examinations in Suzaka city, Nagano Prefecture. 2. All the
      tested infants were prospectively followed until 5 years of age (the middle year
      of day nurseries or kindergartens), when their conditions were diagnosed for
      developmental disorders (mental retardation, pervasive developmental disorder,
      attention deficit hyperactivity disorder). 3. The relation between 1. and 2. was
      analyzed. RESULTS: 1. Acceptable levels for items of the mental development
      screening test were seen in 90% of the infants, except for anxiety with
      unfamiliar faces at 7 months, finger pointing at 1 year, correct picture
      recognition response at 1 year and 6 months, etc. 2. The items with high
      significance levels for chi 2 test and high sensitivity were: 4 items at 7 months
      of age such as anxiety with unfamiliar faces, sitting ability, parachute
      reaction, and others; 5 items at 10 months such as anxiety with unfamiliar faces,
      creeping ability, turning around and looking when called; 8 items at 1 year such
      as use of words with meaning, auditory imitation, finger pointing; 7 items at 1
      year and 6 months such as correct picture recognition response, turning around
      and looking when called, auditory imitation. 3. The items effective for a
      screening test were selected based on clinical experience and on the following
      criteria: public health nurses can conveniently use them at the site of primary
      screening, and that the items can determine the possibility of future
      developmental disorders. 4. The cut off points were set for high specificity and
      sensitivity on scale points to which all the selected items were synthesized, and
      by which follow up rates were within appropriate ranges. CONCLUSIONS: 1. Items of
      mental development screening test with predictive validity for future
      developmental disorders were selected. 2. This study showed that items related to
      interpersonal relationships are highly important. 3. Possibility of future
      developmental disorder can be better determined by using cut off points on a
      scale which utilizes all the selected items, rather than by using individual
      items separately.

PMID- 9175413
TI  - Diabetic neuropathy: prevalence, concordance between clinical and
      electrophysiological testing and impact of risk factors.
AB  - The aim of this study was to assess the prevalence of various forms of diabetic
      neuropathy (DN), by clinical and electrophysiological tests, on 374 diabetic
      patients (66 with type 1 and 308 with type 2 diabetes mellitus) and the
      concordance between clinical and electroneurological alterations and relative
      risk factors impact. The overall prevalence of DN, according to the Saint Antonio
      Conference criteria, was 44.9% (28.88% somatic, 14.44% mixed and 1.60% autonomic)
      without statistical difference between type 2 and type 1 diabetes (46.43% and
      37.88% respectively). In 32.24% of patients nerve conduction velocity (NCV)
      abnormalities were present together with clinical signs or symptoms of
      neuropathy, while 12.68% presented only signs and/or symptoms. In addition 9.36%
      of patients showed alterations of NCV in the absence of clinical signs or
      symptoms of neuropathy. The most frequent form was asymptomatic (30.21%),
      followed by symptomatic neuropathy (12.83%); rare was the severe neuropathy.
      Relative risk increased for diabetes duration > 20 years (p < 0.0001). IN
      CONCLUSION: 1) the Saint Antonio Consensus Conference criteria can be considered
      the most complete test for neuropathy diagnosis; 2) NCV alterations may not be
      concordant with signs-symptoms of neuropathy; 3) the duration of diabetes seems
      to be the most important risk factor.

PMID- 9175414
TI  - A case-control study on lymphocytic subsets in elderly bearing a gastroenteric
      cancer.
AB  - The aim of this work is to evaluate the differences in lymphocytic sub-classes
      between elderly patients with gastroenteric cancer and elderly patients with a
      non neoplastic disease. A group of 88 patients over 60, consecutively admitted to
      the III Division General Surgery for gastro-enteric cancer has been collected for
      the study, the control group consisted of 74 patients also over 60, consecutively
      admitted over the same period for benign abdominal diseases. In all patients the
      following data were measured: body mass index (BMI), white blood cells (WBC),
      total lymphocytes, total T lymphocytes (CD3+), helper T lymphocytes (CD4+),
      suppressor T lymphocytes (CD8+), CD4+/CD8+ ratio, B lymphocytes, CD5+ B
      lymphocytes, activated T lymphocytes (CD3+ HLA-DR+), CD4+ "naive" lymphocytes
      (CD4+ CD45 RA+), CD4+ "memory" lymphocytes (CD4+ CD45 RO+), NK lymphocytes (CD16+
      56+), red blood cells (RBC), total serum cholesterol, albumin, total serum
      proteins. The main lymphocytic subsets were on an average lower in the cancerous
      elderly group with respect to the non cancerous. As the tumour progressively
      increases in size (T), total lymphocytes significantly decrease, while CD4+
      progressively decreases with nodal involvement (N). In the cancerous elderly, we
      found a lower immune response. The immune system appears to be less efficient
      also in association with tumor growth, especially when T and N get worse. The
      response of effector cells to the tumour seems not specific.

PMID- 9175415
TI  - Phytosterol compounds having antiviral efficacy.
AB  - The present study is focused on the antiviral action patterns obtained in vitro
      with synthetic sterolester comprising compositions on virus-bearing host cell
      lines. Appropriate cell-lines were infected with HIV-1, human Cytomegalovirus
      (HCMV) and Herpes simplex virus (HSV). There appears to exist a clear anti
      infective efficacy for a selected number of such ester compounds, provided they
      are formulated into spontaneously dispersible concentrates, which in aqueous
      dilution engender ultramicro-emulsions having micelles in the lowest nanosize
      region. A significant protection against HIV-induced cytopathogenic effect was
      demonstrated employing a methyltetrazolium salt reduction assay on HIV-infected
      MT4 cells when they were incubated with such concentrates. A similar effect was
      evidenced with the same concentrates, when preincubating concentrated virus, but
      not the target cells. Antiviral activity appeared to be remarkable also on HCMV
      infections in vitro, where a blocking effect on immediate-early antigen
      expression in fibroblast monolayers could be observed. Similarly, HSV-associated
      glycoprotein antigen in VERO cells also suggests that virus-cell interaction
      and/or virus multiplication could have been blocked at a very early point of
      time. This would be quite different from antiviral action-patterns studied so far
      and imputed into the current models of explanation. Proper solubilization of the
      employed phytosterol compounds is essential for achieving the described activity
      modes. The often recommended liposome formulations would not be well suited for
      such compounds and such purpose, since after dilution they produce aqueous macro
      emulsions, only. Furthermore, liposome formulations tend to coalesce and exhibit
      Marangoni effects.

PMID- 9175416
TI  - Haemostatic changes in patients with deep vein thrombosis.
AB  - Thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type
      plasminogen-activator (t-PA), plasminogen activator-inhibitor (PAI-1) and
      quantitative determination of functional protein S (PS) were measured using ELISA
      procedures in the plasma of 16 untreated patients with newly-diagnosed deep vein
      thrombosis in the leg and in 10 healthy volunteers. No significant difference in
      plasma TM, t-PA and PS levels was observed among the controls and patients with
      deep vein thrombosis. These patients, on the other hand, showed plasma DD, beta
      TG and PAI-1 levels significantly higher than the control subjects. These data
      show that in patients with deep vein thrombosis a hypercoagulable state is a
      common occurrence.

PMID- 9175417
TI  - Carcinoma of the duodenum: management and survival in 14 cases.
AB  - AIMS: The aim of this study is to evaluate the role of surgery in the treatment
      of adenocarcinoma of the duodenum. METHODS: From 1955 to 1994, 14 patients with
      primary adenocarcinoma of the duodenum underwent surgical treatment in our
      department. Presenting signs and symptoms were mainly related to obstruction and
      bleeding. Upper gastrointestinal contrast study, Computed Tomography (CT) and
      duodenoscopy were the primary diagnostic procedure modalities. All diagnoses were
      confirmed histologically. The tumors were staged pathologically according to the
      new TNM classification (UICC, 1992). Eight patients received palliative treatment
      or exploratory laparotomy. The remaining 6 patients were resectable for cure.
      RESULT: Operative mortality was 35.7%. The 5-year survival rate for patients who
      underwent curative resection was 33.3%. None of the patients who underwent
      palliative procedures or exploratory laparotomy survived for more than 11 months.
      CONCLUSIONS: In the management of resectable adenocarcinomas of the duodenum
      surgical radicality including lymphadenectomy should be pursued. Unresectable
      adenocarcinomas treated with palliative procedure had a very poor prognosis.

PMID- 9175418
TI  - Current etiopathogenetic views in vulvar cancer.
AB  - We considered 59 patients, from 19 to 79 years, treated for vulvar neoplastic
      pathology (32 of 59 had multiple squamous neoplasias of the anogenital region).
      It appeared that vulvar cancer is a disease of aged women and in particular
      between sixty and seventy years, while it isn't common under the age of thirty
      years. It is a hormone-independent pathology. 85% of vulvar malignant tumors is
      constituted by squamous cell carcinomas. The principal risk factors are: 1)
      chronic vulvitis (in particular Lichen sclerosus); 2) leucoplachia, 3)
      immunosuppression, 4) coitus in a young woman with different partners, multiple
      abortions, 5) HPV infection (mostly HPV type 6 and 16), 6) other genital
      carcinomas, 7) capacity to activate or not protoncogenes and to produce
      interferon, 8) tobacco smoking, 9) VIN.

PMID- 9175419
TI  - Biliopancreatic diversion with pylorus-preserving technique: a new method for the
      surgical control of hypercholesterolaemia and diabetes II?
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of biliopancreatic
      diversion by Scopinaro's method, with a pylorus-preserving modification, in
      correcting hypercholesterolaemia and diabetes II not controllable by diet or
      medical treatment. DESIGN: Besides weight loss, Scopinaro's operation produces a
      correction of hypercholesterolaemia and diabetes. These results encouraged us to
      perform BPD without gastric resection, thus preserving the functions of the
      stomach and pylorus in moderately overweight patients with hypercholesterolaemia
      and diabetes. SETTING AND PATIENTS: The pylorus-preserving technique has been
      performed on two patients suffering from severe hypercholesterolaemia and
      hyperglycaemia and who were not more than 30% overweight, at Clinica Chirurgica
      and Chirurgia d'Urgenza Department, University of Sassari, Italy. Both patients
      had a six-month follow-up assessment. MAIN OUTCOME MEASURES. Examination of
      cholesterol and glycaemia levels after the operation, and the moderate weight
      loss. INTERVENTION: The operation is the same as Scopinaro's with regard to the
      length of intestine forming the alimentary loop and the common tract. The
      difference lies in the fact that instead of resecting the stomach and creating a
      gastroileostomy, we resect the duodenum, and perform a duodenoileostomy. RESULTS.
      In both patients the cholesterol and glycaemia levels had returned to normal 1
      month after the operation and are stable after six months. Weight loss was only
      moderate. CONCLUSION: By the preliminary data on two patients treated with our
      modified technique this method seems to be as effective in controlling lipidic
      metabolism and diabetes II as the original version of biliopancreatic diversion.

PMID- 9175420
TI  - Complications of super-selective subarachnoid anesthesia (SSA) with hyperbaric
      bupivacaine: experiences with 355 patients in general and orthopaedic surgery.
AB  - The results obtained from 355 patients of both sexes subjected to general and
      orthopaedic surgery with super-selective subarachnoid anesthesia (SSA) by means
      of small (26-27 gauge) needles with a modified Whitacre needle with ogival point
      are described. The use of thin spinal needles with "pencil-point" type ends
      together with microdoses of local anesthetics has meant a reduction in the
      complications typical of this technique such as hypotension, post-dural puncture,
      headache (PDPH) and urinary retention. Super-selective subarachnoid anesthesia
      realised through an infusion of 0.8-1 ml of hyperbaric bupivacaine is a safe
      effective technique with a low percentage of side-effects.

PMID- 9175421
TI  - Radiolabelled monoclonal antibodies in clinical and surgical oncology: a review.
AB  - Over the past decade, the role of immunoscintigraphy using radiolabelled
      monoclonal antibodies has been steadily growing in clinical oncology, and in
      particular, in radioimmunotherapy and radioimmunoguided surgery for the treatment
      of primary, recurrent, and metastatic colorectal, ovarian, gastric, and prostate
      cancer. Herein, the authors review the requirements for successful tumour
      radioimmunodetection and related procedures.

PMID- 9175422
TI  - Pulmonary edema and acute hypercapnic respiratory failure treated with bi-level
      nasal-CPAP: case report.
AB  - Noninvasive mechanical ventilation has been suggested for the treatment of
      patients with respiratory failure. We describe the case of a patient affected by
      bilateral cystic bronchiectasis and acute hypercapnic respiratory failure, due to
      a cardiogenic pulmonary edema, successfully treated with bi-level nasal-CPAP.
      This report suggests that in some cases noninvasive ventilatory support may mean
      avoiding tracheal intubation, even with critically ill patients.

PMID- 9175423
TI  - Bilateral acute suppurative parotitis due to Staphylococcus aureus: an hospital
      acquired case with fatal outcome.
AB  - During recent decades, acute bacterial parotitis has progressively changed its
      etiological and clinical spectrum. New risk factors and causative agents are
      emerging, while the associated rates of complications and mortality may remain
      still significant. A rare case of concurrent bilateral suppurative parotitis
      caused by Staphylococcus aureus has been observed in a patient hospitalized for
      prior abdominal surgery and multiple underlying illnesses. The disease had a
      complicated and ultimately fatal outcome, despite a timely diagnosis being made
      and a specific treatment started. A literature review dealing with risk factors,
      microbiology, clinical picture, complications, differential diagnosis, treatment
      and outcome of suppurative parotitis is presented.

PMID- 9175424
TI  - Rhodococcus equi pneumonia in a patient with occult HIV infection: successful
      therapy.
AB  - We report a case of Rhodococcus equi cavitary pneumonia in a 37-year-old patient
      with occult HIV infection. Because of his good immune status, the patient was
      given oral erythromycin and rifampin which rapidly resolved the infection. This
      modality of treatment may be sufficient in HIV-positive selected patients fur the
      resolution of Rhodococcus equi pneumonia.

PMID- 9175425
TI  - Adverse drug reaction to rifampin: a case with long lasting antiplatelet
      antibodies.
AB  - Rifampin is a drug able to induce adverse reactions involving both the kidney and
      the hematological system. We observed a case, throughly studied and we deemed
      worth-while to report it, for some important features that were evident.
      Transient hemolytic anemia, recoverable acute renal failure, persistent increased
      titer of anti-platelet antibody lasting also after 3 weeks from the withdrawal of
      the drug and in spite of corticosteroid therapy, could be explained by the immune
      mechanisms that are, therefore, postulated.

PMID- 9175426
TI  - Principles of membrane protein assembly and structure.

PMID- 9175427
TI  - Conformation and design of peptides with alpha,beta-dehydro-amino acid residues.

PMID- 9175428
TI  - Protein conformational substates from X-ray crystallography.

PMID- 9175429
TI  - Mismatch base pairs in RNA.

PMID- 9175430
TI  - The mechanism of 3' cleavage and polyadenylation of eukaryotic pre-mRNA.

PMID- 9175431
TI  - Stimulation of kinase cascades by growth hormone: a paradigm for cytokine
      signaling.

PMID- 9175432
TI  - Oligonucleotides and polynucleotides as biologically active compounds.

PMID- 9175433
TI  - Replication control of plasmid P1 and its host chromosome: the common ground.

PMID- 9175434
TI  - Changes in gene structure and regulation of E-cadherin during epithelial
      development, differentiation, and disease.

PMID- 9175435
TI  - The formation of DNA methylation patterns and the silencing of genes.

PMID- 9175436
TI  - The role of mRNA stability in the control of globin gene expression.

PMID- 9175437
TI  - Self-glucosylating initiator proteins and their role in glycogen biosynthesis.

PMID- 9175438
TI  - Molecular genetics of yeast TCA cycle isozymes.

PMID- 9175439
TI  - On the detection of auditory deviations: a pre-attentive activation model.
AB  - The conscious perception of infrequent deviant sounds occurring in a series of
      frequent standard sounds may in part be based on the output of an obligatorily
      operating deviance detection system. This system encodes invariances inherent to
      the recent auditory stimulation into short-lived representations of auditory
      sensory memory and compares each actual input with these representations. The
      underlying processes may be regarded as preattentive in the sense that they do
      not rely on the explicit intention of a person to detect deviants and that they
      may be active even in the absence of attention (although they may be prone to
      attentional modulations). The output of this feature-specific preattentive
      deviance detection system fuses into an integrated mismatch signal that in turn
      may activate subsequent processes that result in the triggering of a motor
      response.

PMID- 9175440
TI  - Disrupting human auditory change detection: Chopin is superior to white noise.
AB  - A deviant sound in a sequence of standard sounds elicits a neuromagnetic mismatch
      field (MMF) reflecting change detection based on the auditory sensory memory
      trace. To illuminate the nature of this trace, we investigated the effects of
      white noise and music maskers on the MMF. The stimuli were delivered to the
      participant's right ear, and the maskers were delivered to the same or
      contralateral ear. Only maskers containing transients (music) presented to either
      ear abolished the MMF. In parallel, the ability to discriminate the deviants
      decreased dramatically, probably because of integration of transient features of
      the music to the neural representations of standards and deviants. As a result,
      the similarity of these representations prevents change detection. White noise
      affected the MMF amplitude only when presented to the same ear to which the
      stimuli were presented. All maskers decreased the M100 but not the M50 amplitude,
      suggesting that the neural generators behind these responses are functionally
      separate.

PMID- 9175441
TI  - Cardiovascular and neuroendocrine adjustment to public speaking and mental
      arithmetic stressors.
AB  - In this study, we evaluated cardiovascular, neuroendocrine, and psychological
      adjustment to repeated presentations of a public speaking and a mental arithmetic
      task. Brief versions of mental arithmetic tasks have been used widely in previous
      reactivity studies, and growing attention to more socially salient tasks has led
      to the increased use of public speaking tasks. However, psychophysiological
      adjustment during extended and repeated exposure to these tasks has not been
      delineated. In the present study, 52 healthy men worked on three 8-min
      presentations of public speaking and of mental arithmetic in a repeated measure
      design. Both tasks produced substantial cardiovascular, adrenocorticotropic
      hormone, and cortisol responses; public speaking produced greater changes.
      Repeated presentations of public speaking produced a stable pattern of cardiac
      activation, whereas repetitions of the mental arithmetic initially produced large
      cardiac responses that changed to a more vascular tonus across task periods. Both
      tasks increased negative moods. However, correlations between the endocrine,
      cardiovascular, and negative moods were significant only during the public
      speaking stressor. The public speaking task is a socially relevant experimental
      protocol for studying reactivity in the laboratory setting and elicits relatively
      high, stable, and homogeneous responses.

PMID- 9175442
TI  - Prepulse effects on the photic eyeblink reflex: evidence for startle-dazzle
      theory.
AB  - Weak visual prestimulation effects on the early (R50, 50-80 ms) and late (R80, 80
      200 ms) components of the eyeblink response to bright light flashes were studied
      in 16 normal individuals. At a lead time of 120 ms, R50 was inhibited relative to
      no-prepulse control trials, whereas R80 was facilitated. According to the
      proposed startle-dazzle theory, luminance onset transients trigger an initial
      response, R50, that is functionally related to startle. Sustained stimulation
      then activates prolonged eyelid (R80) and pupil responses, which serve to
      minimize retinal bleaching. Although the sensitivity of the photic blink reflex
      to attention is controversial, R50 latency showed a pattern suggestive of
      inhibition of return (Posner & Cohen, 1984, Attention and performance, Vol. X,
      pp. 531-556, Hillsdale, NJ: Erlbaum). Analyses in a patient with unilateral
      occipital lobe damage supported previous evidence that inhibition by a visual
      prepulse requires neocortex, but facilitation does not.

PMID- 9175443
TI  - Temporal stability of lipid responses to acute psychological stress in middle
      aged men.
AB  - The purpose of this study was to establish the temporal stability of lipid
      responses to acute psychological stress. Eighteen men were tested twice an
      average of 16.2 months apart in identical laboratory reactivity protocols. Total
      cholesterol, triglycerides, high- and low-density lipoprotein-cholesterol, plasma
      volume, heart rate, and blood pressure were assessed during rest, serial
      subtraction, and speech. After correction for changes in plasma volume,
      significant elevations were recorded for all variables during the speech task,
      but fewer variables showed changes during the serial subtraction task. Strong
      intersession associations were found when considering levels of the variables
      during baseline and stress (rs > or = .58). Correlations for the change scores
      ranged from .36 to .52 for the atherogenic lipids and from .39 to .87 for the
      cardiovascular variables. Little evidence was found for stability of plasma
      volume changes. There is moderate to high temporal stability of the atherogenic
      lipids when considering rest and stress levels and small to moderate temporal
      stability when considering change scores.

PMID- 9175444
TI  - Different cortical activation patterns in blind and sighted humans during
      encoding and transformation of haptic images.
AB  - In this study, we investigated whether the occipital cortex of blind humans is
      activated during haptic perception and/or transformation of a haptic image. Slow
      event-related brain potentials were monitored from 18 electrodes in 12 sighted
      and 15 congenitally blind participants while they were engaged in a haptic mental
      rotation task. In both groups, slow negative shifts appeared over (a) the frontal
      cortex at the beginning of each processing episode, (b) the left-central to
      parietal cortex during encoding and maintaining of a haptic image, and (c) the
      central to parietal cortex during image transformation. A pronounced slow
      negative potential over the occipital cortex emerged only in the blind
      individuals and was time-locked to the processing epochs. Its amplitude increased
      with the amount of processing load. The slow wave effects observed in the blind
      individuals could indicate that occipital areas participate in specific,
      nonvisual functions or they could reflect a coactivation of these areas whenever
      the activation level of task-specific processing modules located elsewhere in the
      cortex is raised by nonspecific thalamocortical input.

PMID- 9175445
TI  - Temporal characteristics of auditory sensory memory: neuromagnetic evidence.
AB  - We investigated the temporal dependencies of N100 m, the most prominent
      deflection of the auditory evoked response, using whole-head neuromagnetic
      recordings. Stimuli were presented singly or in pairs (tones in the pair were
      separated by 210 ms) at interstimulus intervals (ISIs) of 0.6-8.1 s. N100 m to
      single stimuli and to the first tone of the pair had similar temporal recovery
      functions, plateauing at ISIs of 6 s. N100 m to the second tone in the pair,
      which was smaller than that to the first except with short ISIs, plateaued with
      ISIs of about 4 s. Source analysis revealed that the N100 m could be decomposed
      into two sources separated by about 1 cm on the supratemporal plane. The recovery
      function of the posterior source was not affected by stimulus presentation,
      whereas that of the anterior source was. Activity in the anterior area appears to
      reflect the effects of temporal integration. We relate these results to auditory
      sensory memory.

PMID- 9175446
TI  - Heritability of respiratory sinus arrhythmia: dependency on task and respiration
      rate.
AB  - In this study, we investigated the genetic and environmental origin of individual
      differences in respiratory sinus arrhythmia (RSA) during rest and during four
      stress tasks. We used a multivariate model including age, RSA, and respiration
      rate. Participants were 208 male and female pairs of middle-aged twins. A model
      without sex differences, specifying additive genetic and unique environmental
      factors, showed the best fit across all conditions. Heritability of RSA ranged
      from 28% to 43%. Correction for respiration rate yielded RSA heritabilities of
      similar size. The covariance between respiration rate and RSA was best explained
      by a combination of correlated unique environmental and correlated additive
      genetic factors. Combined with data from an earlier project, RSA from 317
      adolescent and 712 middle-aged individuals of both sexes was available. This
      large data set showed that (a) sex differences in mean RSA are absent and (b) RSA
      decreases considerably from adolescence (111.5 ms) to middle age (60.0 ms).

PMID- 9175447
TI  - Hemodynamic responses to laboratory stressors in children and adolescents: the
      influences of age, race, and gender.
AB  - The objectives of the present study were threefold: (a) to compare the patterns
      of hemodynamic responding of children and adolescents during behavioral
      challenges, (b) to examine whether previously reported cardiovascular reactivity
      differences between Black and White children are dependent on pubertal status,
      and (c) to assess whether gender differences in hemodynamic response reported for
      adults is similar in children. One hundred fifty-nine children (ages 8-10 years)
      and adolescents (ages 15-17 years), equally divided along gender and racial
      lines, participated in a laboratory protocol consisting of a reaction time task,
      a mirror tracing task, a cold forehead challenge, and a stress interview. Results
      indicated that adolescents responded with greater beta-adrenergic activation than
      did children and that gender differences in reactivity often reported for adults
      emerged more clearly in the adolescents than in the children. This study failed
      to replicate prior findings of greater vasoconstrictive responses in Black
      children as compared with White children.

PMID- 9175448
TI  - The effect of emotional and attentional processes on blink startle modulation and
      on electrodermal responses.
AB  - Emotional accounts of startle modulation predict that startle is facilitated if
      elicited during aversive foreground stimuli. Attentional accounts hold that
      startle is enhanced if startle-eliciting stimulus and foreground stimulus are in
      the same modality. Visual and acoustic foreground stimuli and acoustic startle
      probes were employed in aversive differential conditioning and in a stimulus
      discrimination task. Differential conditioning was evident in electrodermal
      responses and blink latency shortening in both modalities, but effects on
      magnitude facilitation were found only for visual stimuli. In the discrimination
      task, skin conductance responses, blink latency shortening, and blink magnitude
      facilitation were larger during to-be-attended stimuli regardless of stimulus
      modality. The present results support the notion that attention and emotion can
      affect blink startle modulation during foreground stimuli.

PMID- 9175449
TI  - The cardiovascular startle response: anxiety and the benzodiazepine receptor
      complex.
AB  - Benzodiazepine receptor (BZR) agonists are prototypic anxiolytic agents, whereas
      BZR inverse agonists exert anxiogenic effects. The effects of these compounds
      offer a potentially important pharmacological model system to examine the central
      mechanisms of anxiety. In accord with its putative anxiogenic properties, we
      previously found that the BZR partial inverse agonist, FG 7142, enhances the
      cardiovascular defensive response to a nonsignal acoustic stimulus in rats. In
      contrast, we found in the present study that this agent attenuates both the
      somatic and cardiovascular components of the acoustic startle response. BZR
      agonists and inverse agonists are known to modulate the basal forebrain cortical
      cholinergic system, and we consider the potential involvement of this system in
      the disparate psychophysiological actions of FG 7142 and in anxiety states in
      general.

PMID- 9175450
TI  - Frequency domain discriminant analysis of the electroencephalogram.
AB  - A frequency domain generalization of the classical quadratic discriminant
      function was applied to the problem of classifying alpha-band multichannel
      electroencephalogram recordings in three task conditions. The data consisted of
      41-channel recordings obtained in eyes closed, verbal, and spatial task
      conditions. Classifier performance was measured by deriving a decision rule from
      a training sample of 42 recordings and then applying the obtained rule to a test
      sample of 46 recordings. The proportion of correct classification was .93 in the
      training sample and .85 in the test sample. The classifier performed better when
      based on the complete cross-spectral matrix than when restricted to power
      spectrum variables. Classification based on a subset of 16 leads reduced the
      overall proportion of correct classification to .79 in the training sample and to
      .70 in the test sample.

PMID- 9175451
TI  - Attentional selection and attentional gradients: an alternative method for
      studying transient visual-spatial attention.
AB  - In two experiments, I employed an alternative method for studying transient
      visual-spatial attention. Instead of using precues, attention was manipulated by
      presenting most stimuli sequentially at predictable locations. In Experiment 1,
      most stimuli appeared in a regular clockwise or counterclockwise order, but some
      were separated by one or both visual meridians from the expected location. In
      Experiment 2, most stimuli were presented successively along the horizontal
      meridian, and some stimuli were separated by one, two, or three positions from
      the expected location. Faster response times and larger posterior P1 and N1
      components as well as enhanced negativities at midline electrodes were found for
      expected-location than for unexpected-location stimuli. These effects were
      partially modulated by the distance of unexpected stimuli from the current focus
      of attention, suggesting the existence of attentional gradients. Moreover, the
      data suggest that the direction of previous attentional shifts and the visual
      meridians play an important role for spatial attention.

PMID- 9175453
TI  - Care in the community.

PMID- 9175452
TI  - REM sleep eye movement counts correlate with visual imagery in dreaming: a pilot
      study.
AB  - Based on the findings of our previously published positron emission tomography
      study, we proposed that recorded eye movements during REM sleep are visually
      targeted saccades. In the present study, we examined the correlation between the
      number of eye movements in REM sleep (EM) and visual imagery in dreaming (V) and
      provided further support for our proposal. All the observations (N = 11) were
      made with one individual to eliminate interindividual variation and were made
      during the second REM sleep period to control for a time-of-night effect. V, with
      or without dream report length partialled out, was strongly associated with EM
      only in the 1-min interval immediately preceding awakening. The time course of
      the association suggests that the strong EM-V association reflects a phasic,
      localized activation of the eye-movement-control system in association with REM
      sleep eye movements.

PMID- 9175454
TI  - The Dutch experience with regard to the training for public health.

PMID- 9175455
TI  - Demographic yearbook 1992: the disease picture of the developed and developing
      worlds compared.

PMID- 9175456
TI  - Utilization of health services among rural women in Gujarat, India.
AB  - This study examined the effects of four sets of factors on use of curative health
      services among rural women living in Gujarat, India. The sets of factors analyzed
      were as follows: (1) the demographic characteristics of the women; (2) the
      characteristics of the household in which they lived; (3) the characteristics of
      the environment in which they lived; and (4) the price and convenience of care.
      The study focused on rural married women aged 17-45 who had at least one child.
      Nested multiple logistic regressions were computed on cross-sectional data to
      assess the simultaneous influences of the independent variables on (1) reports of
      episodes of illness (2) use of curative services among rural women who reported
      an illness and (3) use of a specific service. Four types of service were examined
      as outcomes of interest, namely, private doctors, Aga Khan Health Services
      centres, government health centres, and traditional healers. Other things being
      equal, women's education, income, family structure and kinship affiliation were
      significant predictors of use of service. Women seemed to be more sensitive to
      travel time to the health service and its associated costs (purdah restrictions,
      transportation and time costs) than to the direct costs of service. Factors such
      as women's occupation and sanitation facilities, while associated with use of
      service in the expected direction, were not significant predictors of use of
      service. Implications for health planning are offered, including initiatives to
      implement health promotion and disease prevention programs in addition to
      increasing access to the existing health services. Avenues for future studies are
      suggested, particularly in regard to decision-making processes affecting the
      health-seeking behavior of rural women. It is recommended that such policies and
      studies should consider the cultural environment in addition to the existing
      pluralistic health system.

PMID- 9175457
TI  - A study of the referral patterns of obstetric clinics and the performance of
      receiving neonatal intensive care units in Taiwan.
AB  - To study the referral patterns of obstetric clinics, and the performance of
      receiving intensive care units measured by the survival of transported neonates,
      transport records were collected prospectively between July, 1991 and June, 1992.
      Two hundred and fifty-four transported neonates born in 51 obstetric clinics
      (level I units) in Tainan City and County, in southern Taiwan, were enrolled in
      this study. Nineteen percent of the transported neonates were very low
      birthweight infants (< 1500 g). Nearly equal numbers of them were transported to
      eight district hospitals (level II units) and to a tertiary center (level III
      unit), but these infants were 1.5 times more likely to die in a level II unit
      than a level III unit. In addition, equal numbers of infants assisted by
      mechanical ventilators were transported to level II and III units, but these
      infants were three times more likely to die in a level II unit than a level III
      unit (P = 0.006). Seventy-seven percent of the normal birthweight infants (> or =
      2500 g) were transported to level II units, and the mortality in this group was
      12.3% compared with 0% in those transported to the level III unit. Approximately
      56% of these normal birthweight infants in level II units died of severe birth
      asphyxia. The referral patterns of level 1 units had an unfavorable effect on the
      survival of neonates requiring mechanical ventilation. Enhancing the skills of
      the staff in level I units to recognize and stabilize such infants, elevating the
      capability of level II units in treating some of these cases, and increasing the
      hospital beds for level III care are necessary to increase their chance of
      survival.

PMID- 9175458
TI  - Pre-marriage prevention of thalassaemia: report of a 100,000 case experience in
      Isfahan.
AB  - BACKGROUND: Iran like other middle east countries has a large number of major
      thalassaemics. Due to religious restrictions on abortion, the routine prevention
      of the birth of thalassaemic children by this means is not possible. The aim of
      this study is to describe an alternative means to prevent the birth of
      thalassaemic children. METHODS: From January 1993 to January 1996, 10,000 people
      preparing for marriage were screened for the thalassaemia trait, using CBC and
      HbA2 level measurement. High risk couples were referred for further consultation
      regarding the disease and the means of its prevention. The proposed actions of
      the couples regarding thalassaemia prevention were evaluated immediately after
      consultation and then re-evaluated three months later. RESULT: After the project
      had been running for three years the average of high risk couple initially
      deciding not to marry was 90% and no new cases of thalassemia were detected in
      the children of the screened population. CONCLUSION: Where both members of the
      couple were trait-positive their preferred choice was not to marry, rather than
      to marry and use other or no methods of preventing a thalassemia affected child
      being born to them. Cultural and religious ideas can affect such decisions and in
      some Islamic countries the establishment and use of a genetic counselling centre
      can help prevent most of new thalassaemia cases.

PMID- 9175459
TI  - Reducing the risk after coronary artery bypass surgery: documentation of risk
      factors and communication between hospital and general practice.
AB  - A retrospective descriptive study of patients who had had coronary artery bypass
      surgery was carried out to assess the completeness of recording of risk factors
      in case notes in hospital and in general practice, and to determine the
      prevalence of documented risk factors in patients who have had coronary artery
      bypass surgery. Data from reviews of hospital case notes and questionnaires to
      general practitioners were used to describe the frequency of documenting coronary
      risk factors and preventative advice in case notes and in correspondence between
      general practitioners and hospital doctors. Documentation of risk in hospital
      records revealed that all 102 patients had been assessed for family history,
      hypertension and current smoking, but 9 (9%) had no record of serum cholesterol,
      35 (34%) patients did not have a record of their blood glucose, and in 83 (81%)
      patients there was no evidence that obesity had been assessed. Documentation of
      risk factors in general practice records identified that out of 77 patients, all
      had their blood pressure and smoking status recorded but 29 (38%) had not been
      assessed for hypercholesterolaemia. From the hospital records, the prevalence of
      risk factors in the sample population was 41% for hypertension or raised blood
      pressure, 49% for hypercholesterolaemia, 12% for current smoking and 8% for
      diabetes mellitus. In conclusion, patients who have had coronary artery bypass
      surgery have substantial needs for secondary prevention. A more structured
      approach to risk factor assessment and preventative care should begin as soon as
      the diagnosis of coronary heart disease is made, and should not be postponed
      until the patient has deteriorated to the point of needing bypass surgery.

PMID- 9175460
TI  - Lifestyle and dietary differences in smokers and non-smokers from an Italian
      employee population.
AB  - In a sample of 200 subjects, representative of a population of 1936 civil
      servants, we tested differences in life style, dietary habits and distribution of
      risk factors for CHD between smokers and nonsmokers. The two groups (79 smokers)
      and (121 non-smokers) did not differ significantly by age or sex. The percentage
      of sedentary subjects, of hypercholesterolaemics and of hypertensives was found
      to be particularly high among smokers: 67%, 33% and 30% respectively (vs 59%, 27%
      and 19% in non-smokers). More smokers were obese (11% vs 5%) but mean BMI was the
      same in smokers/non-smokers but showed a higher fat mass; the association of CHD
      risk factors indicates only one significant correlation (P < 0.05) between
      obesity and hypertension. In male smokers, higher values of LDL and triglycerides
      and lower intake of energy, vitamins C and A are observed and these values are
      significantly different than those for non-smokers. In women HDL values are
      higher in non-smokers whereas, in female smokers, the food cholesterol intake is
      particularly high 271 +/- 295 mg. There are also correlations both for the
      anthropometric and clinical parameters and for energy and nutrients, indicating
      that the lifestyle of smokers is less healthy than that of non-smokers. Smokers
      cat vegetables and fruits less frequently and consume more alcohol than non
      smokers, who prefer sweet foods.

PMID- 9175461
TI  - Management of colorectal cancer in three South Thames District Health
      Authorities.
AB  - This study describes the management of colorectal cancer, diagnosed in 1988, of
      residents in three South Thames Districts. Of the 328 cases identified as having
      being diagnosed in 1988, case notes were retrieved on 263 (80%) including 62
      registered by death certificate only. There were 159 cases (61%) of colon cancer
      and 104 cases (39%) of rectal cancer. Of these, 172 cases (68%) were admitted
      electively and 90 (32%) as emergencies. Patients subsequently diagnosed with
      colon cancer had a relative risk of being admitted through emergency (relative to
      rectal cancer patients) of 1.39 (95% C.I.: 1.16, 1.67). Elective admissions
      varied significantly by district of residence (P < 0.0001) ranging from 36-65%
      for colon cancers and from 63-92% for rectal cancers across the three districts.
      Dukes' stage was recorded in only 143 (54%) sets of case notes, with significant
      variation by district of residence in the proportion of elective patients for
      whom a Dukes' stage was indicated (P < 0.01). Two-hundred and thirty-six (90%)
      cases received treatment. Of the treated cases, 233 patients received surgery
      with 29 cases of colon cancer (18%) and 32 cases of rectal cancer (31%) receiving
      adjuvant therapy. The proportions of anterior resection, AP resection and
      colostomies given, varied by district. Patients presenting for elective surgery
      were more likely to be treated by a consultant than patients presenting on
      emergency: the relative risks were 2.58 (95% C.I.: 1.74, 3.82) for colon cancer
      patients and 4.93 (95% C.I.: 2.20, 11.06) for rectal cancer patients. In 44 (26%)
      colon cancer cases and 21 (22%) rectal cancer cases it was explicitly stated that
      the tumour had not been fully resected. For colon tumours the five year relative
      survival rates were 35% (95% C.I.: 21%, 50%), 52% (95% C.I.: 34%, 70%), and 14%
      (95% C.I.: -2%, 30%) in districts A, B and C respectively. The corresponding
      figures for rectal tumours were 45% (95% C.I.: 27%, 64%), 62% (95% C.I.: 41%,
      83%) and 24% (95% C.I.: -1%, 50%). There were wide variations in the
      representation, management of and survival from colorectal cancers across the
      three districts. Differences were significant at the level of district of
      residence, mode of presentation and surgical grade. More assiduous recording of
      Dukes' stage is imperative if consensus is to be achieved on effective
      management. Further work is also warranted on district differences in diagnostic
      and referral protocols.

PMID- 9175462
TI  - Fit for the future? A role for health professionals in housing management.
AB  - The institutions of the welfare state have traditionally catered to some health
      needs through housing interventions. A key strategy has been to award people with
      health problems and mobility difficulties priority access to council rented
      homes. Medical rehousing has required input from both housing managers and health
      professionals, especially public health physicians. This paper draws on a postal
      survey of health advisers to English housing departments to analyse the form, and
      consider the future, of this approach to housing for health.

PMID- 9175463
TI  - An investigation into the possible links between shigellosis and hepatitis A and
      public water supply disconnections.

PMID- 9175464
TI  - Incompleteness of statutory notification of bacterial gastro-intestinal
      infection.
AB  - A study was made of all potentially statutorily notifiable bacterial infections
      diagnosed in faecal samples submitted from symptomatic patients to a single
      microbiology laboratory during a six-month period. Salmonella spp, Campylobacter
      spp or Shigella spp were isolated from 167 patients and 51% of these were
      formally notified (54% of general practice patients and 47% of hospital
      patients). Forty-seven percent of cases of food-poisoning (Salmonella spp. and
      Campylobacter spp) were notified as were 70% of cases of shigella infections.
      Notification was made on average 9.4d after sending a specimen to the laboratory.
      A questionnaire used to ascertain the reasons for non-notification in 80 of 85
      cases elicited replies in respect of 78 patients. Four patients infected with
      Salmonella spp or Campylobacter spp were said not to have been suffering from
      food-poisoning. A variety of reasons was given for failing to notify the others,
      the most common were forgetfulness, not receiving the result of the specimen, or
      believing someone else had made the notification.

PMID- 9175465
TI  - Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in
      a Japanese geriatric hospital.
AB  - A case control study on MRSA infection was carried out, with the purpose of
      evaluating the effect of age, gender, hypoalbuminemia, the limitation of
      activities of daily living (ADL), the administration of antibiotics and the use
      of the new cephems which include third generation cephalosporins and monobactam
      and carbapenems, on the occurrence of MRSA infection among the inpatients in a
      geriatric hospital. From April 1991 to March 1994, 285 patients underwent a
      bacterial culture in the various clinical aspects. 118 patients were positive for
      MRSA, who were then used as cases while 167 patients who were negative for MRSA
      were used as controls. The level of serum albumin and the ADL score were lower in
      the MRSA group than in the non-MRSA group (P < 0.01) while the number of
      antibiotics administered before bacterial culture was greater in the MRSA group
      than in the non-MRSA group (P < 0.01). The third generation cephems were more
      commonly used in the MRSA positive patients than the negative patients (P <
      0.01). Even after controlling for the other factors, hypoalbuminemia (OR = 1.73,
      95% CI = 1.27-2.36), the limited ADL (partially limited vs without limitation: OR
      = 1.88, 95% CI = 1.19-2.96, completely limited vs without limitation: OR = 2.50,
      95% CI = 1.64-3.82), the use of antibiotics other than the third generation
      cephems (vs without antibiotics: OR = 1.73, 95% CI = 1.20-2.50) and the
      administration of the third generation cephems (vs without antibiotics: OR =
      3.12, 95% CI = 2.16-4.50) increased the risk of MRSA infection.

PMID- 9175466
TI  - The contribution of bone densitometry to the diagnosis and treatment of
      osteoporosis.
AB  - OBJECTIVE: It has recently been proposed that a specialist osteoporosis service,
      including bone densitometry, should be made available to those most at risk in
      the UK population. The aim of this study was to evaluate such a service, and in
      particular the role of bone densitometry, in terms of its effect on the diagnosis
      of osteoporosis and clinical management of the disease. METHODS: A retrospective
      data abstraction study was performed to investigate the diagnosis and management
      of patients referred to the Metabolic Clinic, City Hospital Nottingham, with a
      potential diagnosis of osteoporosis. Hospital records were available for 117
      patients, aged between 45 and 59, who had attended the Clinic in a given time
      period and undergone bone mineral density measurement. RESULTS: Forty-eight
      patients (41.0%) had osteoporosis of the lumbar spine. The final diagnosis of
      osteoporosis after attending the clinic was different from that on referral in a
      substantial proportion (62.6%) of cases. Only 48.9% of patients with spinal
      osteoporosis were identified by their referring doctor. The percentage of
      patients receiving treatment for osteoporosis increased from 34.2% to 72.6% after
      attending the clinic. CONCLUSIONS: Measurement of bone mineral density identifies
      cases of osteoporosis who would not otherwise be detected and as a consequence
      contributes to the proportion of patients receiving treatment after referral. The
      osteoporosis service provided by the Metabolic Clinic including measurement of
      bone mineral density was thus found to have a considerable impact on the
      diagnosis and treatment of patients with osteoporosis.

PMID- 9175467
TI  - Proteins, RNAs and chaperones in enzyme evolution: a folding perspective.
AB  - The present roles of RNA molecules as templates and of proteins as cellular
      catalysts may not have always been so clearly defined during evolution. Recent
      work on ribozymes shows that the catalytic activity of early RNAs may have been
      more general than previously thought. How did evolution select proteins, not RNA,
      to be the major biological catalysts? Why were chaperones necessary for the
      evolution of modern protein enzymes?

PMID- 9175468
TI  - Kinetic data reliability.

PMID- 9175469
TI  - Self-consistency of kinetic data.

PMID- 9175470
TI  - The bromodomain revisited.

PMID- 9175471
TI  - GCN5-related histone N-acetyltransferases belong to a diverse superfamily that
      includes the yeast SPT10 protein.

PMID- 9175472
TI  - The CARD domain: a new apoptotic signalling motif.

PMID- 9175473
TI  - RNA editing and hypermutation by adenosine deamination.
AB  - Double-stranded RNA adenosine deaminase (dsRAD) was discovered ten years ago. In
      the intervening decade, research on dsRAD has progressed not only predictably,
      such as with the purification of the enzyme and identification of cDNAs, but also
      in some quite surprising ways. This review covers both areas of progress, but
      will concentrate on the surprises, which include the discovery that dsRAD is a
      member of a larger family of deaminases and the identification of RNAs that
      appear to be targets for these deaminases in vivo.

PMID- 9175474
TI  - RNA editing: getting U into RNA.
AB  - RNA editing in kinetoplastid protozoa remodels the sequences of mitochondrial pre
      mRNAs by the precise insertion and deletion of uridylate residues. These sequence
      changes are directed by small trans-acting RNAs, termed guide RNAs. The basic
      mechanistic pathway by which edited RNA is generated has recently been elucidated
      using in vitro systems capable of a full round of guide-RNA-directed editing.

PMID- 9175475
TI  - Peptides in membranes: tipping the balance of membrane stability.
AB  - This review describes a class of peptides that associate with lipids in membranes
      and are commonly known as 'oblique-orientated peptides'. Owing to an asymmetric
      distribution of hydrophobic residues along the axis of the alpha-helix, such
      peptides can destabilize membranes or lipid cores, thereby facilitating such
      cellular processes as vesicular fusion or protein transport across subcellular
      compartments, as well as remodelling of lipid cores.

PMID- 9175476
TI  - Two-component signal transducers and MAPK cascades.
AB  - Two-component signal transducers, which are characterized by the histidine-to
      aspartate phospho-transfer mechanism, were once thought to be restricted to
      prokaryotes. They have, however, now been identified in diverse eukaryotic
      species including plant, fungus, yeast and slime mold. In yeast, a two-component
      osmosensor has been found to regulate a mitogen-activated protein kinase (MAPK)
      cascade, a ubiquitous eukaryotic signaling module.

PMID- 9175478
TI  - Methods and reagents. Protecting vector DNA from UV light.

PMID- 9175477
TI  - Myc target genes.
AB  - The myc family of proto-oncogenes belongs to the basic helix-loop-helix leucine
      zipper (bHLHZ) class of transcription factors. Myc proteins function as
      transcriptional activators through heterodimerization with Max, but might also
      act as negative regulators of transcription. Identification of genes directly
      controlled by Myc-Max has proved difficult, but recent work is producing a
      growing list of candidates. Results to date suggest that Myc-Max influences cell
      growth and proliferation through direct activation of genes involved in DNA
      synthesis, RNA metabolism and cell-cycle progression.

PMID- 9175479
TI  - Database of HIV proteinase structures.

PMID- 9175480
TI  - Frederick Gowland Hopkins and the unification of biochemistry.

PMID- 9175482
TI  - A large outbreak of epidemic louse-borne typhus in Burundi.

PMID- 9175481
TI  - Expanded programme on immunization (EPI). Lack of evidence that hepatitis B
      vaccine causes multiple sclerosis.

PMID- 9175483
TI  - Experiences of epilepsy surgery in intractable seizures with past history of CNS
      infection.
AB  - We studied the clinical characteristics, location of epileptogenic regions, and
      the surgical outcomes in 18 patients with intractable epilepsy associated with
      previous CNS infections. All patients underwent an extensive presurgical
      evaluation and 11 patients had intracranial EEG monitoring. On the basis of
      presurgical evaluation, epileptic regions were localized to the mesial temporal
      (n = 12) and the neocortical (n = 6) regions. The age of the time of CNS
      infection was significantly younger and the latent period of non-febrile seizures
      after CNS infection was longer in patients with mesial temporal lobe epilepsy
      (MTLE). MRI showed hippocampal atrophy and hippocampal signal changes in 11 of 12
      patients with MTLE. Among 6 patients with neocortical epilepsy (NE) 5 patients
      had normal MRI and one showed cerebral hemi-atrophy. Surgery was successful
      (class I & II) in all patients with MTLE, however, in the patients with
      neocortical epilepsy, seizure-free results were not achieved in any patients
      after resective surgery (6 patients) and only 2 patients achieved Class II
      outcomes after a second epilepsy surgery consisting of neocortical resection.
      Patients with MTLE after CNS infection were differentiated from the group of
      neocortical epilepsy by an earlier onset of CNS infection, a prolonged latent
      period and a higher frequency of meningitis. The characteristic pathology in this
      group was hippocampal sclerosis and the surgical result was excellent.
      Neocortical epilepsy following CNS infection usually had no focal lesion on MRI
      and was associated with a relatively poor surgical result. This study suggested
      that the surgical outcome was influenced by the type of epileptic syndromes
      rather than the etiology of seizures. The association of MTLE with the younger
      age of CNS infections and with meningitis more frequently suggested that the
      neocortical neurons during infancy or early childhood may be more resistant to
      the epileptogenesis, or that the CNS infections in patients with MTLE might be
      milder in severity to cause selective injuries to the hippocampal neurons during
      their vulnerable stage.

PMID- 9175484
TI  - Correlation between the postmortem stature and the dried limb-bone lengths of
      Korean adult males.
AB  - The postmortem stature was measured in 57 Korean adult males (age range: 20-86
      years old, mean: 52.3 years old) in supine position. After dissection of the
      corpses, we measured the maximum length of the remaining limb-bones (humerus,
      radius, ulna, femur, tibia and fibula). The correlation coefficients between the
      stature and each limb-bone length were calculated. Simple regression equations
      for estimating stature from each limb-bone length and multiple regression
      equations from the combination of limb-bone lengths were also obtained.

PMID- 9175485
TI  - Biofeedback assisted relaxation in essential hypertension: short-term follow-up
      of contributing effects of pharmacotherapy on blood pressure and heart rate.
      "Brief communication".
AB  - The present study was designed to evaluate the possible beneficial effects of
      biofeedback-assisted relaxation to pharmacotherapy on blood pressure and heart
      rate in patients with essential hypertension. Twenty patients with essential
      hypertension and without any complications or end-organ damage participated in
      the study. All the patients were using anti-hypertensive drugs. The study
      protocol consisted of an interview, 10 days baseline, 10 biofeedback-assisted
      relaxation sessions and a 10-day post-treatment period. Interview blood pressure
      (BP) and heart rate (HR) measurements, baseline mean values of systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and HR recorded during the 1st,
      10th and 20th minutes of each session and the post-treatment mean values were
      evaluated. Significant differences were found between the mean values of SBP, DBP
      and HR after the whole treatment protocol (Wilcoxon signed-ranks test). The mean
      values of SBP, DBP and HR measurements recorded during the 1st, 10th and 20th
      minutes of the biofeedback-assisted relaxation sessions, which were evaluated by
      repeated measures of ANOVA on ranks test, showed a significant decrease only for
      the 10th minute values at the end of the whole treatment program. Despite a short
      follow-up, it was suggested that these results were encouraging considering the
      fact that once the patients are thoroughly instructed in home practice of
      relaxation and encouraged to develop their own strategies for relaxation, the
      long term outcome may also be promising.

PMID- 9175486
TI  - Efficacy of a topical agent SS-cream in the treatment of premature ejaculation:
      preliminary clinical studies.
AB  - SS-cream is a topical agent for treating premature ejaculation (PE) which is made
      with extracts from 9 natural products. We evaluated the efficacy of SS-cream in
      the treatment of PE. An open pilot study was performed in 186 patients with PE.
      The mean ejaculatory latency from intromission to ejaculation was 1.5 minutes.
      Sixty-four of the 186 patients (34.4%) were combined with mild erectile
      dysfunction in whom penile rigidity was not sufficient to be satisfied in sexual
      activity. Patients were instructed to apply 0.1 gm. of SS-cream on the glans
      penis 1 hour before sexual contact and to wash out the cream before sexual
      intromission. Patients were asked to complete a report form including ejaculatory
      latency, the degree of satisfaction in the sexual lives of both themselves and
      their partners, and any adverse effects after each application. One hundred and
      sixty-six out of 186 patients (89.2%) reported they were satisfied with the
      application of the SS-cream and the mean ejaculatory latency was significantly
      prolonged to 10.89 +/- 5.60 minutes. The mean ejaculatory latency was 9.85 +/-
      3.58 minutes in 52 out of 64 patients (81.2%) with mild erectile dysfunction.
      There was no significant difference in the changes of ejaculatory latencies
      between patients with pure PE and patients with mild erectile dysfunction. Twenty
      patients (10.8%) claimed to have no changes of ejaculatory latencies after the
      application of SS-cream. Adverse effects were noted in 11 patients (5.9%), which
      were mild local irritation symptoms in 7 patients, and delayed ejaculation of
      more than 30 minutes in 4 patients, the symptoms subsided spontaneously within 4
      hours. These results indicate SS-cream is effective in the treatment of PE and
      also PE combined with mild erectile dysfunction with a few side effects. Further
      studies on the action mechanisms of SS-cream and a double blind placebo
      controlled trial are needed.

PMID- 9175487
TI  - Prevention of heterotopic bone formation after total hip arthroplasty using 600
      rad in single dose in high risk patient.
AB  - Nineteen patients received single-dose exposure to 600 rad delivered within 48
      hours of total hip arthroplasty (THA) with shielding of the prosthesis region for
      the prevention of heterotopic ossification. The patients were considered at high
      risk for developing heterotopic ossification (HO) because of hypertropic
      osteoarthritis, post-traumatic osteoarthritis or the presence of previously
      formed ectopic bone. The average follow-up period was 42 months (range, 37 months
      48 months). At a follow-up study, all hips except one were classified as Brooker
      class 0. The single exception was classified as class I. All patients were
      asymptomatic at the last follow-up study and no component demonstrated subsidence
      or radiolucent line indicative of loosening. The authors concluded that 600 rad,
      single-fraction radiation therapy is cost effective, convenient and safe for the
      prevention of heterotopic ossification after total hip arthroplasty.

PMID- 9175488
TI  - Relationship between nutritional intake and dental caries experience of junior
      high students.
AB  - This study was designed to investigate the relationship between nutritional
      intake and caries experience of junior high school students. The sample consisted
      of 295 boys and 356 girls in Kangwha county. Dependent variables were total
      caries experience, occlusal surface caries experience, smooth surface caries
      experience and DMFS score (Decayed, Missing, Filling Tooth Surface score).
      Independent variables such as pit and fissure retentiveness of first molars, oral
      hygiene status, intraoral acidogenicity were also measured by dentists. Other
      independent variables such as toothbrushing habits, socioeconomic conditions,
      between-meal eating habits, and daily nutritional intake were determined during
      an interview. Univariate and multivariate analysis was performed to evaluate how
      nutritional intake influences caries experience. The results were as follows: 1.
      The most influential factor on dental caries experience was pit and fissure
      retentiveness. 2. Dietary fiber and potassium were the significant nutritional
      factors on total caries experience and occlusal caries experience, and niacin was
      the significant nutritional factor on smooth surface caries. 3. DMFS score was
      positively associated with the daily amount of carbohydrate and niacin intake,
      and negatively associated with total energy intake. The above results suggested
      that pit and fissure retentiveness was the most influential factor on caries
      experience. However, in this study, the intake of potassium and niacin was
      identified to influence the caries experience in addition to confirming the well
      known relationship between fiber and carbohydrate intake.

PMID- 9175489
TI  - Extrarenal manifestations of autosomal dominant polycystic kidney disease.
AB  - Recently, with the widespread use of new imaging techniques, the diagnosis of
      autosomal dominant polycystic kidney disease (ADPKD) is increasing. To analyze
      the extrarenal manifestations of ADPKD in Korean patients, we retrospectively
      studied the clinical characteristics of 30 patients with ADPKD. Thirty Patients
      with ADPKD who had been diagnosed at Yongdong Severance Hospital from 1988
      through 1994 were recruited for this study. All patients' past and family
      histories were re-evaluated, and charts and radiologic images were reviewed
      retrospectively. The male to female ratio was 9:21, and the age of initial
      diagnosis was 39.2 +/- 13.8 (mean +/- SD) years. In 15 cases (50%), ADPKD had
      been diagnosed by renal symptoms; in 8 cases (26.7%), by chance during evaluation
      of extrarenal diseases; in 5 cases (16.7%), by family screening; and in 2 cases
      (6.7%), by uremic symptoms. Extrarenal involvement included hepatic cysts (70%),
      pancreatic cysts (16.7%), splenic cysts (6.7%), thyroid cysts (6.7%), inguinal
      hernia (3.3%), and colonic diverticula (3.3%). In 5 cases (16.7%), cardiac
      valvular abnormalities were noted by echocardiography. Seven patients underwent
      hemodialysis, and the duration from the initial diagnosis to initiation of
      dialysis was 9.9 +/- 8.5 (mean +/- SD) years. We investigated the extrarenal
      manifestations of 30 cases of ADPKD in Koreans, which were also common and
      clinically important as renal manifestations. Renal cysts are only one of a
      myriad of renal and extrarenal manifestations of ADPKD. ADPKD should be managed
      systematically since this disorder is a systemic disease with clinically
      important involvement of the cardiovascular system, the gastrointestinal tract,
      the genitourinary system, and the musculoskeletal system.

PMID- 9175490
TI  - P53 overexpression in gastric adenocarcinoma with Helicobacter pylori infection.
AB  - Gastric carcinogenesis has been studied in various aspects. Helicobacter pylori
      (Hp) infection and mutation of the p53 tumor suppressor gene have recently been
      argued to be important factors of gastric carcinogenesis. There have been many
      studies to determine the precise mechanism of how Hp is related to gastric
      cancer, but it is so far still unknown. We studied the relationship of Hp
      infection and p53 overexpression and tried to discover some significance in
      clinicopathologic factors such as age, sex, stage, site, differentiation and
      gross morphology. Ninety-six patients who were diagnosed with gastric cancer at
      Severance Hospital, Yonsei University Medical College from November 1995 to March
      1996, and 96 control patients of non-ulcer dyspepsia (NUD) were studied by
      endoscopic biopsy of normal gastric tissue and cancer tissue. They also underwent
      the CLO (Delta West, Melbourne, Western Australia) test for Hp positivity and p53
      immunohistochemical stain for p53 positivity. These data were analyzed for
      comparison with the clinicopathologic characteristics of gastric cancers. In
      conclusion, the differentiated group cancer had a significantly high Hp
      positivity and p53 positivity. There is a possibility that Hp infection and p53
      tumor suppressor gene mutation might be significantly related in the gastric
      carcinogenic process of well- and moderately-differentiated adenocarcinomas, but
      further study is necessary to determine more direct clues on the carcinogenic
      roles of these factors.

PMID- 9175491
TI  - Evolution of the ITS sequences of ribosomal DNA in Enteromorpha (Chlorophyceae).
AB  - Ribosomal DNA (rDNA) region, including the 3' end of the 18S rRNA gene, the
      entire 5.8S rRNA gene, the 5' end of the 28S rRNA gene, and the internal
      transcribed spacers ITS 1 and ITS 2, of Enteromorpha green algae from the Baltic
      Sea, were sequenced. The evolution of the Enteromorpha sequences differed from
      those of other green algae in several important ways. The ITS regions were short
      and had a high nucleotide bias. The frequency of nucleotides G and C was up to
      70% in the ITS sequences, whereas the frequencies were close to 50% in the 5.8S
      rDNA. Furthermore, the sequence divergence was much higher in ITS 1 than in ITS
      2. Two haplotypes, differing only by two nucleotides, were detected in the E.
      intestinalis/compressa complex. The difference coincides with a morphological
      differentiation (branching of thalli) and may represent distinct gene pools.

PMID- 9175492
TI  - The origin and distribution of the Lund Y chromosome in Microtus agrestis
      (Rodentia, Mammalia).
AB  - The Lund Y (Lu-Y) chromosome of the field vole (Microtus agrestis) is
      distinguished from the standard Y (St-Y) by its much longer short arm. G-banding
      revealed that the Lu-Y originated by a pericentric inversion in the St-Y.
      Chromosome analysis of 297 male field voles from 92 localities in Fennoscandia.
      Germany, and England, in addition to data from the literature, made it possible
      to map the distribution area of the Lu-Y. It is restricted to the south-western
      parts of Sweden. The question of when and where the Lund Y population originated
      is discussed. Adding data from a hybrid zone (Jaarola et al. 1997) and from
      females, totally 491 specimens from 120 localities were analyzed without
      detecting any variation in chromosome number and autosome morphology. Other cases
      of intraspecific Y chromosome polymorphism in mammals, and the use of Y
      chromosome variants as population genetic markers, are discussed.

PMID- 9175495
TI  - Genetic and phenotypic analysis of the genes of the elbow-no-ocelli region of
      chromosome 2L of Drosophila melanogaster.
AB  - The elbow locus is found to be two genes elA and elB, each of which has a
      distinct phenotype when mutant. Mutations of the elA gene have a strong phenotype
      where the wing is markedly disrupted. Mutations of elB are weak, mainly affecting
      the alula and the wing bristles. The two genes are dominant enhancers of each
      other. Homozygous deletion of the complete elbow region results in lethality.
      Situated between the elbow genes is the pupal gene and a locus which when deleted
      causes a crippled leg phenotype. This locus may be a control region for elbow.
      Immediately adjacent on the proximal side of elA is the no-ocelli locus. The
      phenotypes of noc alleles vary from extreme, where the ocelli and associated
      bristles are absent, to weak where these structures are disrupted. The various
      noc phenotypes are associated with genetically distinct gene regions, mutations
      of which act as enhancers of each other. Alleles of el and noc show partial
      failure of complementation, heterozygotes having weak el or weak noc phenotypes.
      Alleles of both these genes interact with the antimorphic noc allele Sco.

PMID- 9175494
TI  - The X bivalent in fetal bovine oocytes.
AB  - Wholemount preparations of oocytes from fetal bovine ovaries were examined in an
      attempt to study the incidence and type of chromosomes involved in pairing
      irregularities during different stages of early ovarian differentiation.
      Synaptonemal complexes exhibiting pairing irregularities were noted in meiocytes
      of all age groups. However, asynapsis and partial synapsis were more frequently
      noted in X chromosomes at the onset of meiosis in fetal bovine ovaries while the
      frequencies of similar errors in autosomes were relatively low and remained
      unchanged in the age groups included in this study. The significance and
      mechanisms of X chromosome asynapsis in excess of that expected on the basis of
      numerical ratio of the X to the bovine meiotic complement, are not known at
      present. We hypothesize that changes in the transcriptional status involving
      activation, inactivation, and reactivation of the X chromosomes during embryonic
      and ovarian differentiation on the conceptus, in addition to the inactivation
      undergone by the paternal X chromosome prior to fertilization, could be a factor
      rendering them susceptible to structural changes which, in turn may increase the
      incidence of sex chromosome asynapsis at the onset of meiosis in female fetuses.

PMID- 9175496
TI  - Fine structure of gene frequency landscapes in domestic cat: the Old and New
      Worlds compared.
AB  - The dependence of variance of coat gene frequencies on geographic distance was
      studied in stray domestic cat populations by means of analysis of variance
      (ANOVA) and variance ratio test (F-test) with the data set containing 333
      samples. The procedure included the stepwise estimation of variances within
      square pieces of territory of gradually increasing size performed separately for
      the Old and New Worlds. It is revealed that beginning with 200-300 km-size of
      square side, for the most loci studied, these distance-controlled variances are
      significantly less in the New World, thus indicating a smoother gene frequency
      landscape. In both worlds, the tb and t alleles show significantly higher
      variances than the other mutant alleles. The mean allele frequencies in the New
      World are significantly higher than in the western European area, from where
      colonization took place for alleles that constitute a "luxury" gene group (O, d,
      l, W) presumably formed by human preference. The results support in general the
      historical/immigration hypothesis, i.e., that domestic cat colonization of the
      New World proceeded by rapid population expansion without a great gene frequency
      change (bottleneck-like effect). A modification is suggested for the model: a
      biased colonization sample (a founder effect) in regards to O, d, l, and W
      alleles.

PMID- 9175497
TI  - Pesticides in canals of South Florida.
AB  - Atrazine, ametryn, bromacil, simazine and norflurazon were the most frequently
      detected pesticides in surface water samples and DDE, DDD and ametryn were the
      most frequently detected pesticides in sediment samples collected over the period
      November 1991 to June 1995 in a monitoring network that includes 27 stations in
      south Florida canals. The 744 pesticide detections during this time period
      represent about 2% of the total number of analytical determinations. Many of the
      most frequently detected compounds were used in large amounts in the monitoring
      area based on pesticide usage estimates included in this study. Spatial trends in
      pesticide detections followed use patterns. The maximum atrazine detections
      occurred in winter to late spring and were associated with usage on turfgrass and
      agricultural products. Endosulfan residues above the Florida water quality
      criterion were occasionally observed in surface water in the Homestead area and
      most of the exceedences occurred in confined waters. Methods with lower MDLs have
      recently been developed and should increase the number of detections in future
      sampling. Pesticides which bind strongly to soil, pesticides that are highly
      persistent and those used in large amounts were some of the more frequently found
      pesticides in sediments.

PMID- 9175498
TI  - Dissipation and distribution of atrazine, simazine, chlorpyrifos, and tetradifon
      residues in citrus orchard soil.
AB  - An environmental fate study was conducted in a citrus orchard plot in Valencia
      (Spain) in the fall of 1993. Dissipation and distribution of atrazine, simazine,
      chlorpyrifos and tetradifon residues following their controlled addition for
      agricultural purposes in a mediterranean red soil (Luvic Calcisol, Rhodoxeralf)
      were evaluated. During a two-month period, the amounts of applied pesticides in
      different soil layers (0-0.05, 0.05-0.22, 0.22-0.42, and 0.42-0.52 m) were
      monitored. In addition, information on soils, weather and agricultural practice
      were collected. Degradation half-lives were calculated, assuming zero-order
      kinetics: 11 days for atrazine, 12 days for simazine, 10 days for chlorpyrifos,
      and 18 for tetradifon. The distribution through the soil profile shows that the
      pesticide concentrations were always highest in the upper layer (0-0.05 m) of
      soil, and that atrazine was the most mobile of all the four pesticides
      investigated.

PMID- 9175499
TI  - Comparative sensitivity of Selenastrum capricornutum and Lemna minor to sixteen
      herbicides.
AB  - Aquatic plant toxicity tests are frequently conducted in environmental risk
      assessments to determine the potential impacts of contaminants on primary
      producers. An examination of published plant toxicity data demonstrates that wide
      differences in sensitivity can occur across phylogenetic groups of plants. Yet
      relatively few studies have been conducted with the specific intent to compare
      the relative sensitivity of various aquatic plant species to contaminants. We
      compared the relative sensitivity of the algae Selenastrum capricornutum and the
      floating vascular plant Lemna minor to 16 herbicides (atrazine, metribuzin,
      simazine, cyanazine, alachlor, metolachlor, chlorsulfuron, metsulfuron,
      triallate, EPTC, trifluralin, diquat, paraquat, dicamba, bromoxynil, and 2,4-D).
      The herbicides studied represented nine chemical classes and several modes of
      action and were chosen to represent major current uses in the United States. Both
      plant species were generally sensitive to the triazines (atrazine, metribuzin,
      simazine, and cyanazine), sulfonureas (metsulfuron and chlorsulfuron), pyridines
      (diquat and paraquat), dinitroaniline (trifluralin), and acetanilide (alachlor
      and metolachlor) herbicides. Neither plant species was uniformly more sensitive
      than the other across the broad range of herbicides tested. Lemna was more
      sensitive to the sulfonureas (metsulfuron and chlorsulfuron) and the pyridines
      (diquat and paraquat) than Selenastrum. However Selenastrum was more sensitive
      than Lemna to one of two thiocarbamates (triallate) and one of the triazines
      (cyanazine). Neither species was sensitive to selective broadleaf herbicides
      including bromoxynil, EPTC, dicamba, or 2,4-D. Results were not always
      predictable in spite of obvious differences in herbicide modes of action and
      plant phylogeny. Major departures in sensitivity ofSelenastrum occurred between
      chemicals within individual classes of the triazine, acetanilide, and
      thiocarbamate herbicides. Results indicate that neither species is predictively
      most sensitive, and that a number of species including a dicot species such as
      Myriophyllum are needed to perform accurate risk assessments of herbicides.

PMID- 9175500
TI  - Detection of toxic organometallic complexes in wastewaters using algal assays.
AB  - Chlorella (a unicellular green alga) and Cladophora (a filamentous alga) were
      used in algal assays to identify the presence and toxicity of organometallic
      complexes in four industrial wastewaters. Toxicities of inorganic Pb and
      organometallic compounds (trimethyl, tetramethyl and tetraethyl leads, cacodylic
      acid and Cu-picolinate) were examined, using algal cells grown in 10% BBM
      solution. Inorganic Pb and organometallic compounds altered the fine structure of
      Chlorella cells in a distinguishable manner. X-ray microanalysis revealed that
      organometallic compounds accumulated in the neutral lipids of Cladophora cells.
      By applying the above techniques to the wastewater assays, two of the four
      wastewaters tested were found to contain organometallic complexes. Wastewater
      from a chemical company contained only traces of organo-Cu, but one mining
      effluent contained significant quantities of organo-Cu and organo-Pb, and traces
      of organo-Cr and organo-Tl (thallium). These studies suggest that X-ray
      microanalysis of algae may be a useful tool in identifying aquatic systems
      contaminated with metals and organometallic compounds.

PMID- 9175501
TI  - Evaluation of bleached kraft mill process water using Microtox(R), Ceriodaphnia
      dubia, and Menidia beryllina toxicity tests.
AB  - To determine whether a 7- to 10-d embryo toxicity/teratogenicity test with the
      inland silverside fish, Menidia beryllina, is a sensitive indicator for
      evaluation of bleached kraft mill effluents, we compared this test with the
      Microtox(R) 15-min acute toxicity test and the Ceriodaphnia dubia 7-d chronic
      toxicity test. Water samples used in each test were collected from three areas in
      a bleached kraft pulp and paper mill using a 100% chlorine dioxide bleaching
      process: 1) river water prior to use in the mill; 2) the combined acid/base waste
      stream from the pulping process prior to biological treatment in the aerated
      stabilization basin (ASB); and 3) the effluent from the ASB with a retention time
      of approximately 11 d. Relative toxicity determined by the three tests for each
      water sampling location was compared. All three toxicity tests were predictive
      indicators of toxicity; however, the C. dubia and M. beryllina tests were the
      more similar and sensitive indicators of toxicity. Process water (ASB influent)
      prior to biological treatment in the ASB was toxic at all concentrations using
      the Microtox(R) and C. dubia tests. The fish embryo test showed no toxicity at 1%
      concentrations, slight toxicity at 10%, and acute toxicity at the 100% ASB
      influent concentration. Tests with biologically-treated ASB effluent indicated a
      substantial reduction in observed toxicity to Microtox(R) bacteria, C. dubia, and
      M. beryllina. No toxic responses were observed in any test at a 1% ASB effluent
      concentration which was the approximate effluent concentration in the receiving
      river following mixing. No relationship was found among any toxicological
      response and effluent levels of adsorbable organic halides, polychlorinated
      phenolic compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8
      tetrachlorodibenzofuran, total suspended solids, color, chemical oxygen demand,
      or total organic carbon.

PMID- 9175502
TI  - Psyllids as a potential source of heavy metals for predators.
AB  - Contents of Al, Fe, Zn, Cu, Cd, Mn, Ni, and Hg were determined in 14 species of
      psyllids and in leaves of their host plants from unpolluted sites (Finland) and
      industrially polluted sites in Poland. Generally, psyllids accumulated low
      amounts of metals, but their metal burdens increased with age. Exuvia were
      important for the elimination of Al, Ni, and Mn, and larval wax for Al, Cu, and
      Ni. Biomagnification of metals, expressed as the concentration factor (cf) was
      low (cf: 0.56-1.08) for Mn, Al, and Ni, but high for Cd (cf: 5.86). Trioza
      chenopodii, Cacopsylla ulmi, and Psylla betulae represented the
      microconcentrators (cf: 0.9-1.25); the remaining species were the
      macroconcentrators (cf: 2.0-4.9). In polluted areas Psyllopsis fraxini eliminated
      large amounts of Al, Fe, Cu, Mn, and Cd with honeydew. This way of metal
      elimination was of less importance in species from unpolluted sites. Adults of
      Cacopsylla mali, P. fraxini, P. betulae, and Cacopsylla sorbi fall a prey to ants
      and may be important in transfer of Zn, Fe, Cu, Cd, and Ni. In comparison with
      aphids their role in metal transfer is marginal, due to better self-defence
      mechanisms and higher mobility, which protect them from potential predators and
      parasites.

PMID- 9175503
TI  - The effects of used motor oil, silt, and the water mold Saprolegnia parasitica on
      the growth and survival of mole salamanders (genus Ambystoma).
AB  - Amphibians appear to be declining worldwide. One cause of their decline may be
      used crankcase oil which leaks from motor vehicles and washes into ponds. Once in
      ponds, the oil may either be directly toxic to amphibians, or may indirectly
      affect them by disrupting food chains. The effects of oil may also be compounded
      by naturally occurring materials in the water column such as silt. Silt may
      interfere with respiration across gill surfaces. This study examined the effects
      of oil and silt on the growth and metamorphosis of larval mole salamanders,
      Ambystoma opacum and A. tigrinum tigrinum. In Experiment One it examined ponds
      with and without silty water and oil pollution to determine their suitability as
      habitats for salamander larvae. In Experiment Two it studied the effects of low
      levels of oil combined with silt on animals raised in the laboratory and fed prey
      items not raised in oil. In Experiment Three, it explored the effects of oil at
      an ecosystem level by raising the salamanders in the field in plastic
      micromesocosms that mimicked small ponds. Finally, in Experiment Four, in the
      laboratory, it examined the short-term survival of salamanders in high
      concentrations of oil. This study found that ponds containing oil and silt
      produce salamanders of reduced size and weight. Furthermore, while salamanders
      are relatively robust to the short term effects of large concentrations of used
      motor oil, oil has deleterious effects on the community and therefore exerts an
      indirect negative effect on salamanders. In the mi- cro-mesocosms containing oil,
      salamanders were smaller and weighed less than animals not raised in oil.
      Furthermore, silt results in reduced growth, earlier metamorphosis, and increased
      susceptibility to the water mold Saprolegnia parasitica.

PMID- 9175505
TI  - The effects of tetrachloroguaiacol on the growth, survival, and development of
      the fathead minnow, Pimephales promelas.
AB  - Fathead minnow (Pimephales promelas) larvae were exposed for 7 days to
      tetrachloroguaiacol (TeCG), within 24 h of hatching, at concentrations of 0, 25,
      50, 100, 200, 400 microg/L. No significant difference in growth or larval
      survival was found among treatments. Embryos, within 24 h of fertilization, were
      also exposed to TeCG at concentrations of 0 and 100 microg/L for 10 days. No
      significant difference was found between the control and treatment groups for
      larval survival, body length, body width, or for yolk size of the
      eleutheroembryos. However, a significant difference was found in the hatching
      success of the eggs (p = 0.05). Since fathead minnows have been known to spawn in
      areas close to sites that discharge bleached kraft mill effluent (BKME) which
      contains TeCG, into receiving waters, naturally occurring populations will likely
      be affected by the toxicant.

PMID- 9175504
TI  - Photoinduced toxicity of fluoranthene to seven marine benthic crustaceans.
AB  - Seven marine benthic crustaceans were exposed in 4 d water-only toxicity tests to
      five concentrations of fluoranthene. After exposures, mortality (LC50) and the
      ability to bury in clean sediment (EC50) were determined. Survivors were then
      exposed to UV radiation for 1 h. The differences between LC50s and EC50s before
      and after UV exposure were used to assess photoinduced toxicity. UV exposure
      enhanced fluoranthene toxicity by as much as tenfold in five of the seven species
      tested (Rhepoxynius abronius, Eohaustorius estuarius, Leptocheirus plumulosus,
      Grandidierella japonica, and Corophium insidiosum). Species having the greatest
      potential for natural exposure to sunlight (Excirolana vancouverensis and Emerita
      analoga) were the least sensitive to photoinduced fluoranthene toxicity. Although
      photoinduced toxicity needs to be considered in environmental risk assessments,
      testing should be done, using ecologically relevant species and exposures.

PMID- 9175506
TI  - Assessment of cerebral hemispheric symmetry in hatchling chickens exposed in ovo
      to polychlorinated biphenyl congeners.
AB  - Previous investigators have reported that exposure to a mixture of environmental
      contaminants, including polychlorinated biphenyls, results in morphologic
      asymmetry of the cerebral hemispheres in hatchling great blue herons (Ardea
      herodias) and have suggested that this asymmetry may be a useful biomarker for
      contamination. This study was made to determine whether exposure to PCB congeners
      3,3',4,4'-tetrachlorobiphenyl (IUPAC #77) and 3,3',4,4',5-pentachlorobiphenyl
      (IUPAC #126) causes similar asymmetry in hatchling domestic chickens (Gallus
      domesticus). Eggs were injected at day 0 of incubation with either a high dose,
      low dose, or combination of each congener. At hatching, the chicks were perfused
      with 10% formalin-saline. The brains were removed, sectioned and stained with
      cresyl violet. Width and height measurements of each hemisphere were taken at
      eight locations, caudal to rostral, 400 microm apart starting at the level of the
      anterior commissure (CA) and ending at the lobus paraolfactorius (LPO). The
      absolute differences between measurements of the left and right sides were used
      to run a univariate split plot analysis of variance to determine if the amount of
      asymmetry present was associated with specific congeners or doses. Significant
      differences in asymmetry were found between noninjected control groups and
      vehicle-injected control groups (p </= 0.05), but not between noninjected
      controls and treatment groups. A first degree orthogonal polynomial contrast
      analysis illustrated a linear trend with asymmetry increasing from the most
      caudal section at the CA to the most rostral section at the LPO for both non
      injected control and treatment groups (p </= 0.05). These data indicate that
      asymmetry may be normal in avian brains resulting from both intrinsic structural
      asymmetry and extrinsic molding forces acting on the head during development.
      Both of these factors should be taken into consideration when assessing the
      usefulness of cerebral asymmetry as a biomarker.

PMID- 9175507
TI  - Arsenic residues in eggs from laying hens fed with a diet containing arsenic
      (III) oxide.
AB  - Three groups of six hens each were fed for twelve days with diets containing 7.5,
      15.0, and 30.0 mg arsenic per kg in the form of As2O3. A control group was
      included in the trial. The hens from each group were formed into three subgroups.
      The eggs of two hens, laid in three days, formed a composite sample. The As
      concentration in the egg whites and yolks was determined in duplicate by
      radiochemical neutron activation analysis. With increasing As concentration in
      the poultry feedstuff, its concentration in egg yolk and white also increased,
      but a plateau appears to be reached quite rapidly. The ratio between the As
      concentration in yolk and in white is nearly constant (1:3) for all three groups
      of hens, irrespective of the level of As in the feed. The concentration of
      arsenic in dry matter of whites was significantly higher than in the dry matter
      of yolks, while the concentrations of arsenic in fresh samples of yolks were
      higher in the comparison with fresh samples of whites, but the differences were
      not significant.

PMID- 9175508
TI  - Behavior of captive american kestrels hatched from o,p'-dicofol exposed females.
AB  - A two-generation laboratory study was conducted on captive American kestrels
      (Falco sparverius) to investigate the possible behavioral alterations from the
      compound o,p'-dicofol. Paired females were exposed to three levels of dicofol by
      oral gavage. Adults of the second generation, exposed only via the maternal dose
      of o,p'-dicofol at 5- and 20-mg/kg, displayed negatively correlated changes in
      reproductive behaviors. Second generation females showed a significant difference
      (p < 0.05) from control birds in the miscellaneous behavior category, where more
      time was spent picking at the rope perch, watching flies, laying down on the
      perch and other such displacement activities. Second generation 5-mg/kg males
      completed significantly fewer copulations (p < 0.05) than the corresponding
      control birds. The number of attempted or failed food transfers (a pair bonding
      activity) was also significantly higher (p < 0.05) in the second generation 5
      mg/kg male group. Trials were conducted on second generation males to determine
      aggressiveness of these individuals when placed in a competitive arena. Primary
      perch sites and food items were obtained by control birds significantly (p <
      0.05) more often than dicofol-exposed males. A bird's maternal dose had a
      significant negative effect (p < 0.05) on its ability to achieve a high rank
      order position.

PMID- 9175509
TI  - The urinary excretion of arsenic metabolites after a single oral administration
      of dimethylarsinic acid to rats.
AB  - The biotransformation following oral administration of dimethylarsinic acid
      (DMA), an organoarsenical herbicide and the main metabolite of inorganic arsenic
      in mammals, was studied in rats. Male F344/DuCrj rats were administered a single
      dose of DMA (50 mg/kg) orally. Urine was collected at 0, 2, 4, 8, 10, 24, and 48
      h after administration by forced urination. Arsenic metabolites in urine were
      analyzed by ion chromatography with inductively coupled plasma mass spectrometry
      (IC-ICP-MS). The proportions of urinary elimination of DMA, trimethylarsine oxide
      (TMAO), methylarsonic acid (MMA), an unidentified arsenic metabolite, and
      arsenite were determined at various timepoints after administration.
      Unmetabolized DMA was the most common form excreted during the first 4 h.
      Thereafter, a gradual decrease in the proportion of DMA was observed, while
      progressive increases in those of TMAO, the unidentified metabolite, and arsenite
      occurred. The proportion of TMAO excreted amounted to over 50% of all arsenic in
      urine between 6 and 24 h. The proportion of the unidentified metabolite and
      arsenite were each approximately 10% at 10 and 24 h after administration. The
      findings indicate that DMA administered to rats was initially excreted as
      unchanged DMA, and later as the methylated metabolite, TMAO. Arsenite, a
      demethylated metabolite of DMA, also was excreted later than elimination of DMA
      and TMAO. The hypothesis of demethylation by intestinal microorganisms can be
      supported by comparing the metabolites following oral and intraperitoneal
      administration. The unidentified metabolite was readily decomposed by HCl but was
      left unchanged by NaOH; these findings suggest that it was present in a complexed
      form in urine.

PMID- 9175510
TI  - Comparative evaluation on the biological monitoring of exposure to parathion and
      its methyl analog.
AB  - The effects of both parathion and methyl parathion on the inhibition of plasma
      cholinesterase were elaborated in a rat model employing a modified isocratic
      reverse-phase HPLC method coupled with UV detection for the determination of the
      urinary metabolite p-nitrophenol (U-4NP). A linearity of r2 > 0.995 was found for
      a standard curve ranging from 0.06 to 0.96 microg/mL with a % relative error of
      </= +/- 10% and a recovery of 89 +/- 2%. The % CV at all levels was </= 11%. A
      linear correlation was observed between the oral administration of parathion and
      methyl parathion for both the percent inhibiton of cholinesterase as well as the
      urinary elimination of 4NP. It is tentatively recommended that an U-4NP of 2. 0
      mg/g creatinine be established as a biological exposure index (BEI) for methyl
      parathion.

PMID- 9175511
TI  - Impact of carbofuran in the oocyte maturation of catfish, Heteropenustes fossilis
      (Bloch).
AB  - Investigations were undertaken to observe the influence of technical grade
      carbofuran (CF) on the egg maturational processes of catfish, Heteropneustes
      fossilis (Bloch). Fish were exposed to sublethal doses (0.5, 1, and 2 mg/L) of CF
      for 30 days at 25 +/- 1 degrees C. Control fish were maintained in water. The
      gonado-somatic index (G.S. I. = ovarian weight x 100/body weight) of the fish,
      treated with 1 or 2 mg/L CF, was decreased significantly compared to that of the
      controls. The inhibition was almost at the same level in these doses. CF at the
      dose of 0.5 mg/L was found to be ineffective. From the histomorphological
      observations of the ovary, it was observed that CF altered both the area and the
      percentage occurrence of the various types of primary oocytes in the ovary
      compared to that of the control fish. The stage I primary oocytes were
      predominantly higher in CF-treated fish than stage II and stage III which was
      reversed in control animals. The degeneration of follicular walls, connective
      tissues and vacuolization in the ooplasm of the stage II and III oocytes were
      observed in CF-treated fish (0.5-2 mg/L). It appears that CF at sublethal
      concentrations inhibits oocyte maturational processes in catfish.

PMID- 9175512
TI  - Antimony in drinking water, red blood cells, and serum: development of analytical
      methodology using transversely heated graphite furnace atomization-atomic
      absorption spectrometry.
AB  - An atomic absorption spectrometric (AAS) method has been developed for
      determining microg/L levels of Sb in samples of water and blood. The AAS method
      is based on the concept of stabilized temperature platform furnace atomization
      (STPF) realized through the use of a transversely heated graphite atomizer (THGA)
      furnace, longitudinal Zeeman-effect background correction, and matrix
      modification with palladium nitrate-magnesium nitrate-nitric acid. The method of
      standard additions is not mandatory. The detection limit (3 standard deviations
      of the blank) is 2.6 microg Sb/L for the water, red blood cells (RBCs), and serum
      samples. Data are presented on the degree of accuracy and precision. The THGA-AAS
      method is simple, fast, and contamination-free because the entire operation from
      sampling to AAS measurement is carried out in the same tube. The method has been
      applied to the determination of Sb in some leachate tap water samples derived
      from a static copper plumbing system containing Sn/Sb solders, and in small
      samples (0.5 ml) of RBCs and serum derived from rats given Sb-supplemented
      drinking water.

PMID- 9175513
TI  - Acute and chronic toxicity of azinphos-methyl to two estuarine species,
      Mysidopsis bahia and Cyprinodon variegatus.
AB  - The acute and chronic toxicity of azinphos-methyl (Guthion) was evaluated for two
      estuarine species in the laboratory. Mysids (Mysidopsis bahia) and sheepshead
      minnows (Cyprinodon variegatus) were selected as the representative invertebrate
      and vertebrate estuarine test species, respectively. The toxicological endpoints
      determined for each species included the 96-h LC50, the no-observed-effect
      concentration (NOEC), the maximum acceptable toxicant concentration (MATC), and
      the acute-to-chronic ratio. The 96-h LC50 value derived for sheepshead minnows
      (2.0 microg/L) was seven times higher than the 96-h LC50 value (0.29 microg/L)
      derived for mysids. The MATCs were 0.024 microg/L and 0.24 microg/L for the mysid
      and the sheepshead minnow, respectively. The estimated acute-to-chronic ratios
      were 12 for mysids and 8.3 for sheepshead minnows.

PMID- 9175515
TI  - PCB congener accumulation by periphyton, herbivores, and omnivores.
AB  - The concentrations of 20 polychlorinated biphenyl (PCB) congeners were measured
      in periphyton, herbivorous fish (stoneroller minnows, Campostoma anomalum), and
      omnivorous fish (striped shiners, Luxilus chrysocephalus) in an industrially
      contaminated stream and a reference stream in eastern Tennessee. The sum of the
      concentrations of the 20 congeners, normalized by dry mass, was one to two orders
      of magnitude higher in stonerollers and shiners than in periphyton. Normalizing
      PCB concentrations by lipid mass reduced concentration differences between
      periphyton and stonerollers, but PCBs per unit lipid in stonerollers were still
      50-350% higher than those in periphyton. Shiners had significantly higher lipid
      specific PCB concentrations than did stonerollers, so a trophic hierarchy of
      primary producer < herbivore < omnivore was evident in lipid-specific PCB
      concentrations. Differences in lipid type, exposure duration, and exposure
      sources may account for the trophic-level differences in total PCBs. Congener
      profiles were roughly similar in periphyton, stonerollers, and shiners: five
      congeners (IUPAC numbers 101, 110, 138, 153, and 180) constituted >60% of the
      total mass of PCBs analyzed in all three trophic levels. However, stoneroller and
      shiner tissue was enriched in congeners 153, 118, and 187 relative to periphyton;
      congeners 153 and 187 are resistant to metabolic breakdown by monooxygenases
      found in fish liver. Principal component analysis of congener percentages
      separated periphyton from fish and distinguished between sampling locations.

PMID- 9175514
TI  - Characterization of the H4IIE rat hepatoma cell bioassay for evaluation of
      environmental samples containing polynuclear aromatic hydrocarbons (PAHs).
AB  - The H4IIE rat hepatoma cell bioassay has been extensively used to assess the
      toxic equivalents (TEQs) of complex mixtures of halogenated aromatic hydrocarbons
      in environmental samples. However, there is often a discrepancy between bioassay
      induction results and toxic equivalents calculated from chemical analysis of
      samples; the former generally yield higher bioassay-TEQs. Polynuclear aromatic
      hydrocarbons (PAHs) are a class of chemicals which can significantly contribute
      to induction-TEQs. Benzo(a)pyrene (BAP), dibenz(a, h)anthracene (DBA),
      benz(a)anthracene (BA), benzo(k)fluoranthene (BkF), benzo(b)fluoranthene (BbF),
      chrysene (Chr), and indeno(1,2,3-c,d) pyrene (IdP) are carcinogenic PAHs found in
      environmental samples, including oysters collected from Galveston Bay. The
      induction potency of these PAHs relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) was determined individually in rat hepatoma H4IIE cells seeded in 6-well
      plates, and the induction-derived equivalency factors (EFs) relative to TCDD were
      0. 000354, 0.00203, 0.000025, 0.00478, 0.00253, 0.00020, 0.0011 for BAP, DBA, BA,
      BkF, BbF, Chr, and IdP, respectively. Dilutions of a reconstituted PAH mixture
      containing 23 PAHs (744 to 4466 ng/g total PAHs) with constant percentages of BAP
      (4.5%), DBA (3.5%), BA (2.4%), BkF (3.7%), BbF (3.5%), Chr (4.7%), and IdP (4.2%)
      yielded bioassay-derived induction-EQs that ranged from 0.52 to 1.44 ng/g.
      Oysters exposed in the laboratory to the same PAH mixture for 30 days
      differentially accumulated the PAHs with time. Bioassay-EQs for these oyster
      extracts ranged from 0.94 to 5.79 ng/g. These results were similar to the
      chemically calculated EQs which varied from 0.81 to 3.13 ng/g.

PMID- 9175516
TI  - Rock-shells (Thais clavigera) as an indicator of As, Cu, and Zn contamination on
      the Putai Coast of the black-foot disease area in Taiwan.
AB  - This study presents the distribution of arsenic (As), copper (Cu), and zinc (Zn)
      in various seafoods-oysters (Crassostrea gigas), false fusus (Hemifuscus tuba),
      venus clams (Cyclina sineasis), green mussels (Perna viridis), blood clams (Arca
      granosa), flounders (Psettodes erumei), and rock-shells (Thais clavigera)
      collected from the Putai coast of the black-foot disease (BFD) area in Taiwan.
      Special attention is paid to evaluate the relationships among As, Cu, and Zn and
      effect of body size on metal concentration in Thais clavigera. Maximum Zn and Cu
      geometric mean (GM) concentrations (GM = 615 and 376 microg/g, dry wt,
      respectively) are found in oysters (Crassostrea gigas), and the values are much
      higher than those of the other organisms by about 1.7-208 and 1.8-375 times,
      respectively. Similarly, Thais clavigera has a high capacity for accumulating Cu
      and Zn collected from the same location. One interesting point is that relatively
      high As concentrations (GM = 65.7 microg/g, dry wt) in Thais clavigera are found
      as compared with those in other organisms (range from GM = 2.37 to 40.2 microg/g,
      dry wt). The As concentrations are significantly higher in Thais clavigera (1.62
      27.7 times) than those in other organisms (p < 0.05), except for the false fusus
      (Hamifuscus tuba). A linear regression analysis shows a significant increase in
      Zn concentration with increasing Cu concentration in Thais clavigera. On the
      other hand, the As concentration is correlated with Cu and Zn concentrations (r =
      0.77 and 0.77, respectively; p < 0.05) in Thais clavigera. Double logarithmic
      plots of metal content and concentration against dry-body weight and shell length
      show linear relationships. The result indicates that large individuals have
      higher contents of Cu, Zn and As, and have slopes of 1.58, 1.38, and 1.34,
      respectively. In addition, metal concentrations against shell length for all
      animal sizes also indicate that Cu, Zn and As have slopes of 1.92, 1.18, and
      1.11, respectively. In conclusion, Thais clavigera has a high capactiy for
      accumulating As, Cu, and Zn and is a potential bioindicator for monitoring As, Cu
      and Zn.

PMID- 9175517
TI  - Nitrite mediated T lymphocyte responses in the intestinal immune system of mice
      infected with Trichinella spiralis nematode.
AB  - The effects of orally administered sodium nitrite (20 mg NaNO2/kg b. w) on the
      responses of T and B lymphocytes collected from the mesenteric lymph nodes were
      studied in resistant AKR/J, H-2(k) haplotype mice infected with Trichinella
      spiralis nematode. On days 6, 9, and 12 postinfection, the mesenteric lymph node
      cells (MLNC) were collected from the mice and assayed for lymphocyte subsets
      (CD4(+), CD8(+), B220(+)), cytokines (IL-2, IL-5), and INF-gamma. At the same
      time, the number of adult worms in the small intestine were counted. Infection of
      the nitrite-treated mice with T. spiralis L1 larvae caused a marked increase in
      the number of adult worms in the small intestine. However, preincubation of T.
      spiralis L1 larvae with nitrite before infecting the mice resulted in a
      significant reduction in the number of adult worms (p < 0.05). Preincubation of
      T. spiralis L1 larvae with nitrite also caused an increase in the number of
      CD4(+) and CD8(+) cells as well as IL-2, IL-5, and INF-gamma levels. An increased
      level of CD8(+) subsets and a depression of IL-2 and IL-5 production by MLNC were
      observed in mice infected with larvae without nitrite pretreatment. Since
      supplementary rIL-1alpha was found to alter INF-gamma secretion by MLNC in vitro,
      the pattern of MLNC proliferation was examined further with the nitrite-treated
      mice. Sodium nitrite increased thymidine incorporation into the MLNC. However,
      INF-gamma production was not enhanced when rIL-1alpha was added to the MLNC
      culture obtained from nitrite-treated mice.

PMID- 9175518
TI  - Genetic factors in the development of cardiovascular anomalies.

PMID- 9175519
TI  - Mitochondrial cardiomyopathy: molecular and biochemical analysis.
AB  - Abnormalities in cardiac mitochondrial respiratory enzymes and mitochondrial DNA
      have been found in an increasing number of pediatric cases of both dilated and
      hypertrophic cardiomyopathy, giving rise to the entity known as mitochondrial
      cardiomyopathy. Histochemical, biochemical, and molecular findings are described
      in this review of mitochondrial cardiomyopathy, which should provide assistance
      in its diagnostic identification.

PMID- 9175520
TI  - Genetic predisposition to cardiomyopathies.

PMID- 9175521
TI  - On-line automated border detection for echocardiographic quantification of right
      ventricular size and function in children.
AB  - Rapid, accurate assessment of right ventricular (RV) size is important for the
      management of children with congenital heart disease. The usefulness of the
      Acoustic Quantification system of automated border detection (ABD) and on-line
      quantification (AQ) for assessment of RV size was tested in 36 children. AQ data
      were compared to "corrected AQ" measurements (after correction for cavity areas
      erroneously included in the region of interest) required for AQ. Furthermore, the
      influence of necessary changes to gain settings was tested in "lateral gain
      control" (LGC) images obtained by removal of ABD overlays. All results were
      compared to conventional echocardiography (echo), and agreement with magnetic
      resonance imaging (MRI) RV areas was assessed. Systematic differences (+/-)
      limits of agreement with MRI (transverse plane) for conventional echo and AQ
      (apical four-chamber view) were as follows: end-diastolic -0.8 +/- 3.8
      (conventional echo) versus -1.7 +/- 4.6 (AQ) cm2/m2 (p < 0.001); end-systolic 
      1.3 +/- 3.2 versus -4.9 +/- 5.8 (AQ) cm2/m2 (p < 0.001); fractional area change
      7.8 +/- 17.0% versus 26.9 +/- 31.4% (AQ) (p < 0.001). Differences between
      conventional echo, LGC, and corrected AQ areas were not statistically
      significant. The best agreement between MRI and echocardiography was with
      conventional echo. We conclude that automated border detection of the RV can be
      performed successfully with the AQ system at a fixed point in the cardiac cycle.
      For adequate assessment of RV function manual corrections of online AQ results
      are still required, which results in an important reduction of the time gain of
      on-line quantification.

PMID- 9175522
TI  - What is the prevalence of congenital heart diseases?

PMID- 9175523
TI  - Echocardiographic prediction of neonatal ECMO outcome.
AB  - Cardiopulmonary physiology was assessed by Doppler echocardiography in neonates
      undergoing pre-ECMO evaluation for meconium aspiration syndrome, congenital
      diaphragmatic hernia, persistent fetal circulation, and sepsis, from March 1987
      through July 1992 (n = 136). Percent survival by diagnosis was: meconium
      aspiration syndrome, 86%; persistent fetal circulation, 68%; congenital
      diaphragmatic hernia, 63%; sepsis, 33%. Survival odds by diagnosis predicted a
      better outcome for meconium aspiration syndrome than for congenital diaphragmatic
      hernia and sepsis, and a better outcome for persistent fetal circulation than for
      sepsis. Percent survival for right-to-left patent ductus arteriosus flow (PDA)
      was 56%; other patent ductus arteriosus flow was 84%. In multivariate analysis,
      percent survival in congenital diaphragmatic hernia and persistent fetal
      circulation patients with right-to-left PDA flow suggested a worse outcome (%
      survival right-to-left vs other: congenital diaphragmatic hernia, 13% vs 70%;
      persistent fetal circulation, 25% vs 85%), whereas percent survival did not
      appear to suggest the same in meconium aspiration syndrome or sepsis patients.
      Similar analysis in non-ECMO patients suggested a worse outcome with right-to
      left PDA flow in patients with meconium aspiration syndrome and congenital
      diaphragmatic hernia. Right-to-left PDA flow, sepsis, and congenital
      diaphragmatic hernia were associated with a poorer ECMO outcome. Initial
      assessment of PDA flow helps predict ECMO outcome.

PMID- 9175524
TI  - Prenatal diagnosis of severe aortic stenosis.
AB  - We sought to identify echocardiographic markers that might be useful for managing
      fetuses with significant aortic stenosis. The study was a retrospective review of
      fetal echocardiographic studies and postnatal outcomes of all fetuses diagnosed
      with significant aortic stenosis who did not have a hypoplastic left ventricle on
      the initial echocardiogram. Where possible, fetal echocardiographic measurements
      included the aortic, mitral, pulmonary, and tricuspid valve annulus sizes; left
      ventricular dimensions and volume; septal and left ventricular wall thicknesses;
      and echocardiographic Doppler interrogation of the left heart and oval fossa.
      Observations also included an assessment of ascites, pericardial effusion, and
      endocardial fibroelastosis. Prenatal measurements were compared to postnatal
      outcomes. Four patients (group 1) had either clinically successful relief of
      their aortic obstruction (n = 3) or required no intervention (n = 1). Five
      fetuses evolved to the hypoplastic left heart syndrome (group 2). These infants
      demonstrated little or no growth in left ventricular, aortic valve, or mitral
      valve dimensions on serial examination. They also more often exhibited mitral
      stenosis, severe restriction of interatrial shunting, and early to mid second
      trimester left ventricular dilatation. Serial measurements of fetal cardiac size
      and function are helpful for predicting the postnatal outcome of fetuses with
      aortic stenosis.

PMID- 9175525
TI  - Echocardiographic evidence of improved hemodynamics during inhaled nitric oxide
      therapy for persistent pulmonary hypertension of the newborn.
AB  - To evaluate the cardiovascular effects of inhaled nitric oxide (NO) on the
      systemic and pulmonary circulations, 25 consecutive infants with severe
      persistent pulmonary hypertension of the newborn (PPHN) underwent serial
      echocardiographic evaluations before and during inhaled NO therapy. Estimation of
      the systolic pulmonary artery pressure (SPAP) was derived from measurement of a
      tricuspid regurgitant jet using Bernoulli's equation. We also derived a
      pulmonary/systemic pressure ratio to evaluate overall cardiopulmonary effects.
      Paired measurements of estimated SPAP decreased from 62.0 +/- 3.8 mmHg to 44.7 +/
      4.3 mmHg (p < 0.01) during inhaled NO therapy. The pulmonary/systemic pressure
      ratio decreased from 0.98 +/- 0.06 to 0.59 +/- 0.04 during NO therapy (p < 0.01),
      indicating a significant decline in the vascular resistance between the two
      circulations. These changes also correlated with changes in the extrapulmonary
      shunt patterns at the ductus arteriosus and foramen ovale seen during inhaled NO
      therapy. The decreased right-to-left shunting was accompanied by a parallel (64%)
      improvement in systemic oxygenation, with the alveolar-arterial oxygen gradient
      (A-a DO2) falling from 591 +/- 14 mmHg to 380 +/- 33 mmHg (p < 0.01). We found
      echocardiography to be a useful clinical tool for evaluating and monitoring
      pulmonary artery pressure in infants with PPHN. Measurement of the SPAP and the
      pulmonary/systemic pressure ratio gave a quantitative estimation of the severity
      of PPHN, and the extrapulmonary shunt flow patterns at the ductus arteriosus and
      foramen ovale gave qualitative estimates of its severity. Inhaled NO increased
      pulmonary blood flow and oxygenation and improved the systemic cardiopulmonary
      hemodynamics in this group of infants.

PMID- 9175526
TI  - Carotid artery approach to balloon aortic valvuloplasty in infants with critical
      aortic valve stenosis.
AB  - We compare the clinical efficacy of two approaches for balloon aortic
      valvuloplasty (BAV) in infants with critical aortic valve stenosis. The
      approaches were through the carotid artery and the femoral artery. Eight
      catheterizations for BAV were performed in seven consecutive patients with
      critical aortic stenosis: four BAVs were approached through the femoral artery
      and four through the right common carotid artery. We inserted a 5F sheath into
      the right common carotid artery by a cutdown procedure; after BAV the sheath was
      removed and the carotid arteriotomy sutured with 7-0 monofilament. Two cases in
      which the femoral artery approach was used resulted in failure to perform BAV;
      two cases had complications. All four cases with the carotid artery approach were
      successful, with no complications; aortography performed 3 months after one
      balloon valvuloplasty revealed a smooth, unobstructed right carotid artery. Use
      of the carotid artery approach may reduce serious complications with BAV and
      offers quicker, easier maneuvering in infants and neonates with critical aortic
      valve stenosis.

PMID- 9175527
TI  - Supranormal cardiac output in the dopamine- and dobutamine-dependent preterm
      infant.
AB  - To evaluate the incidence of low cardiac output in preterm infants with
      respiratory distress syndrome (RDS), we measured cardiac output, stroke volume,
      heart rate, mean arterial blood pressure, and systemic vascular resistance at 8
      48 hours of age in 30 preterm infants with RDS who were dependent on inotropic
      support. We then compared them to 23 normotensive preterm infants with RDS and 27
      preterm infants without RDS. RDS infants had a higher cardiac output and lower
      systemic vascular resistance and blood pressure than infants without RDS. Infants
      treated with dopamine and dobutamine had a higher cardiac output and heart rate
      than infants on dopamine alone or the normotensive controls but a lower blood
      pressure and systemic vascular resistance than the normotensive controls.
      Supranormal cardiac output (>400 ml/min/kg) was detected in 57% of the infants in
      the dopamine + dobutamine subgroup (p = 0.009) versus 17% in the normotensive RDS
      subgroup and 12% in the dopamine subgroup. These data show that high cardiac
      output is relatively common in infants with RDS dependent on dopamine and
      dobutamine but is not reflected in the blood pressure.

PMID- 9175528
TI  - Normal ranges of heart rate variability during infancy and childhood.
AB  - Heart rate variability is a noninvasive index of the neural activity of the
      heart. The present study examined heart rate variability indices in 210 infants
      and children aged 3 days to 14 years to obtain normal ranges for all age classes.
      Heart rate variability was measured by calculating mean RR interval over the
      length of the analysis, mean RR interval during quiet sleep, 5 time-domain (SDNN,
      SDNN-i, SDANN-i, r-MSSD, pNN50), and 4 frequency-domain (VLF, LF, HF, LF/HF
      ratio) indices. Our data show a significant positive correlation between all
      indices and the mean RR interval over the length of the analysis, except for the
      LF/HF ratio for which the correlation was binomial. A positive power correlation
      was also found between all parameters and age. The multiple correlation analysis
      confirmed the independent effect of age and mean RR interval on the heart rate
      variability. These data in a healthy pediatric population confirm a progressive
      maturation of the autonomic nervous system during childhood and may be utilized
      to examine the effects of underlying disease processes or therapeutic
      interventions on cardiac autonomic tone during infancy and childhood.

PMID- 9175529
TI  - Unique association of a rapidly growing right atrial myxoma in a child with
      double-outlet right ventricle.
AB  - We describe a patient with double-outlet right ventricle in whom a large right
      atrial myxoma developed over approximately 6 months. This patient represents the
      first case described of a right atrial myxoma occurring in an unoperated patient
      with congenital heart disease other than an isolated atrial septal defect.
      Because the child was followed with serial echocardiograms, we can document the
      rapid growth of the tumor.

PMID- 9175531
TI  - Apoptosis: is cell death a crucial step in cardiac development?

PMID- 9175530
TI  - Left-side pulmonary vein obstruction after arterial switch operation in infants
      with D-transposition of the great arteries.
AB  - We describe two cases of left-side pulmonary vein obstruction observed after the
      arterial switch operation (Jatene) for D-transposition of the great arteries.
      This appears to be related to left-sided pulmonary vein obstruction occurring
      coincidently with D-transposition of the great arteries, rather than a
      consequence of arterial switch operation.

PMID- 9175532
TI  - Novel approach to transvenous pacemaker implantation in a post-fontan adolescent.
AB  - Postoperative bradycardia is not uncommon following the Fontan procedure in
      patients with a functional single ventricle. The surgical connections created
      with various Fontan modifications may complicate access to the atria for
      transvenous implantation of a permanent pacemaker. We describe approaches to
      overcoming problems with atrial access in an adolescent with complex congenital
      heart disease who required permanent transvenous atrial pacing for tachycardia
      bradycardia after Fontan surgery.

PMID- 9175533
TI  - Pseudoinfarction pattern in an infant.
AB  - A 4-week-old female infant presented with congestive heart failure, moderate
      mitral regurgitation, and an electrocardiographic pattern of anterolateral
      myocardial infarction. Angiography revealed normal coronary arteries and moderate
      mitral regurgitation. A single-catheter electrophysiology study confirmed the
      presence of an accessory atrioventricular conduction pathway.

PMID- 9175534
TI  - Cardiac arrhythmias and genetics.

PMID- 9175535
TI  - Anomalous origin of the left coronary artery from the pulmonary artery associated
      with ventricular septal defect and mitral stenosis.
AB  - We report a case of a child with ventricular septal defect, mitral stenosis, and
      patent ductus arteriosus, who was also found to have anomalous origin of the left
      coronary artery from the pulmonary artery. Preoperative diagnosis allowed
      successful surgical correction.

PMID- 9175537
TI  - An audible shunt murmur in atrial septal defect.

PMID- 9175538
TI  - FORUM: Is Ecotourism Sustainable?
AB  - / It is legitimate to ask whether and in what form tourism might contribute to
      sustainable development. This is not the same as sustainable tourism which, as a
      single-sector approach to development, may overlook important linkages with other
      sectors. If tourism is to contribute to sustainable development, then it must be
      economically viable, ecologically sensitive and culturally appropriate.
      Ecotourism is often advocated as being a sustainable form of tourism but
      imprecision in terminology clouds basic issues and there are strong economic,
      ecological, and cultural reasons for believing that, even in its purest forms,
      ecotourism is likely to present substantial challenges to destination areas,
      particularly if it competes for scarce resources and displaces existing uses and
      users. Sustainable tourism and ecotourism are not synonyms, many forms of
      ecotourism may not be sustainable, and if ecotourism is to contribute to
      sustainable development, then careful planning and management will be
      required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

PMID- 9175539
TI  - Climate Convention Implementation: An Opportunity for the Pacific Island Nations
      to Move Toward Sustainable Energy Systems
AB  - / The impacts of global warming are among the more serious environmental threats
      for the Pacific Island countries. These nations justifiably argue that developed
      countries should give immediate priority to the implementation of climate change
      mitigation policies because of the severe nature of potential greenhouse impacts
      for the Pacific Islands. Another immediate priority acknowledged by these nations
      is the need for development of adaptation policies that plan for adjustment or
      adaptation, where possible, to the foreshadowed impacts of climate change. This
      article does not focus on adaptation or mitigation policy directly but on an
      allied opportunity that exists for the Pacific Islands via the auspices of the
      Climate Convention, because the existing very costly energy systems used in the
      Pacific Island region are fossil-fuel dependent. It is argued here that efforts
      can be made towards the development of energy systems that are ecologically
      sustainable because Pacific Island nations are eligible to receive assistance to
      introduce renewable energy technology and pursue energy conservation via
      implementation mechanisms of the Climate Convention and, in particular, through
      transfer of technology and via joint implementation. It is contended that
      assistance in the form of finance, technology, and human resource development
      from developed countries and international organizations would provide
      sustainable benefits in improving the local Pacific Island environments. It is
      also emphasized that mitigation of greenhouse gas emissions is not the
      responsibility of the Pacific Islands as they contribute very little on a per
      capita global scale and a tiny proportion of total global greenhouse gas
      emissions.KEY WORDS: Pacific Islands; Climate change; Renewable energy; Framework
      Convention on Climate Change.

PMID- 9175540
TI  - Specific Contributions of Politics, Economics, and Toxicology in Setting Socially
      Consensual Limit Values
AB  - / Limit values are legal limits for the concentrations of substances in the
      environment. They must be agreed upon in a consensual procedure between science,
      economics/technology, and political forces. This is a crucial political
      precondition for their social acceptance. The arguments put forward to justify
      their expediency and numerical level are based not only on risk-benefit
      considerations but also on the aspect of the technical avoidability of direct and
      indirect exposure. The critical assessment of the direct benefit of specified
      exposures falls within the responsibility of economics/technology, whereas
      criteria for their potential adverse effects (direct and indirect) are provided
      by medicine/biochemistry and/or ecology. Within this concept, the avoidance of
      nonbeneficial-even if not openly adverse-exposure is the essential aim of
      environmental hygiene and should be promoted by politics/science. In general,
      society or segments thereof reject adverse, accept beneficial, and tolerate
      unavoidable exposure. Conflicts of interest arise when different groups of
      society simultaneously define a given exposure as being adverse, beneficial, and
      unavoidable. Therefore, from the viewpoint of society as a whole, an optimal
      exposure lies as far as reasonably achievable at a level lower than known or
      plausible adverse effect thresholds (as defined by toxicology or ecology). This
      optimal level of exposure must be determined using a transparent and, hence,
      public procedure.KEY WORDS: Legal limit values; Benefit threshold; Social
      acceptance; Social tolerability; Adverse effect threshold; Avoidable exposure;
      Tolerance threshold; Environmental hygiene

PMID- 9175541
TI  - Simple Words and Fuzzy Zones: Early Directions for Temporary River Research in
      South Africa
AB  - / Although a large proportion of South Africa's rivers are nonperennial,
      ecological research into these systems has only recently been initiated.
      Consequently, we have little verified information about the ecological
      functioning of these rivers or knowledge of how best to manage them. High water
      demands in a semiarid region results in the flow of most perennial rivers being
      altered from permanent to temporary in sections, through impoundment, land-use
      changes, abstraction, etc. Conversely, sections of many temporary rivers are
      altered to perennial as a result of interbasin transfers or may be exploited for
      surface water. Effective and appropriate management of these modifications must
      be based on sound scientific information, which requires intensified, directed
      research. We anticipate that temporary river research in South Africa will, of
      necessity, be driven primarily by short-term collaborative efforts and
      secondarily by long-term ecological studies. At the outset, a simple conceptual
      framework is required to encourage an appreciation of current views of the
      spatial and temporal dynamics of nonperennial rivers and of the variability and
      unpredictability that characterize these systems. We adopt the view that
      perennial and episodic/ephemeral rivers represent either end of a continuum,
      separated by a suite of intermediate flow regimes. A conceptual diagram of this
      continuum is presented. In the absence of a functional classification for
      temporary rivers, a descriptive terminology has been systematically devised in an
      attempt to standardize definition of the different types of river regimes
      encountered in the country. Present terminology lacks structure and commonly
      accepted working definitions. KEY WORDS: Temporary rivers; Intermittent rivers;
      Continuum; Terminology; Classification; Ecosystem management; South Africa

PMID- 9175542
TI  - PROFILE: Hungry Water: Effects of Dams and Gravel Mining on River Channels
AB  - / Rivers transport sediment from eroding uplands to depositional areas near sea
      level. If the continuity of sediment transport is interrupted by dams or removal
      of sediment from the channel by gravel mining, the flow may become sediment
      starved (hungry water) and prone to erode the channel bed and banks, producing
      channel incision (downcutting), coarsening of bed material, and loss of spawning
      gravels for salmon and trout (as smaller gravels are transported without
      replacement from upstream). Gravel is artificially added to the River Rhine to
      prevent further incision and to many other rivers in attempts to restore spawning
      habitat. It is possible to pass incoming sediment through some small reservoirs,
      thereby maintaining the continuity of sediment transport through the system.
      Damming and mining have reduced sediment delivery from rivers to many coastal
      areas, leading to accelerated beach erosion. Sand and gravel are mined for
      construction aggregate from river channel and floodplains. In-channel mining
      commonly causes incision, which may propagate up- and downstream of the mine,
      undermining bridges, inducing channel instability, and lowering alluvial water
      tables. Floodplain gravel pits have the potential to become wildlife habitat upon
      reclamation, but may be captured by the active channel and thereby become
      instream pits. Management of sand and gravel in rivers must be done on a regional
      basis, restoring the continuity of sediment transport where possible and
      encouraging alternatives to river-derived aggregate sources.KEY WORDS: Dams;
      Aquatic habitat; Sediment transport; Erosion; Sedimentation; Gravel mining

PMID- 9175544
TI  - Regulatory Oversight of Genetically Engineered Microorganisms: Has Regulation
      Inhibited Innovation?
AB  - / Using detailed interviews with company representatives and researchers in the
      field, this paper examines the factors that might account for the slow pace of
      development of genetically engineered microorganisms (GEMs) intended for
      environmental release. We specifically analyzed the role of the regulatory system
      in shaping innovation. We identified at least two cases where industry decided to
      discontinue the development of a genetically engineered microbial product because
      of concerns over regulatory oversight. However, most often industry decisions to
      continue or halt development of GEMs were based on an evaluation of the
      particular product's efficacy and potential for profitability. Thus the inability
      of GEMs to perform up to expectations in the field, rather than the regulatory
      constraints, appears to be the factor responsible for the slow pace of
      development. KEY WORDS: Genetically engineered microorganisms; Biotechnology;
      Regulation of biotechnology; Innovation; Environmental release

PMID- 9175545
TI  - RESEARCH: Managing Mountainous Degraded Landscapes After Farmland Abandonment in
      the Central Spanish Pyrenees
AB  - / Plant succession and pasture resources have been studied in abandoned fields of
      the central Spanish Pyrenees, in an environment severely affected by strong
      demographic pressure in the past. Several hydromorphological features (runoff and
      sediment yield) were also analyzed for different environments of the abandoned
      fields, in order to forecast the effects of their reclamation and transformation
      into areas for livestock use. The availability and accessibility of pastures as
      well as soil and water conservation is related to the process of colonization of
      Genista scorpius. Under a dense shrub cover both runoff and sediment yield are
      strongly controlled. As the shrub cover becomes open, sediment yield and runoff
      increase greatly. A dense herbaceous cover yields high runoff coefficients but
      moderate soil losses. From the results obtained, the possibility of abandoned
      field reclamation by means of selective clearing of scrub is discussed.KEY WORDS:
      Abandoned fields; Plant succession; Degraded environments; Soil erosion; Runoff;
      Spanish Pyrenees

PMID- 9175546
TI  - Investigation and Long-Term Monitoring of Phragmites australis Within Virginia's
      Constructed Wetland Sites
AB  - / The use of constructed wetlands to replace natural wetlands is becoming
      pandemic. An investigation using global positioning system technology to map the
      vegetated communities of 15 of the largest constructed wetlands in Virginia
      reveals that 80% are colonized by the invasive species, Phragmites australis
      Trin., and/or aggressive species, Typha spp. Tidally influenced wetlands that
      have subtidal perimeter ditches have significantly less (P < 0.05) P. australis
      in the wetland interior than those without perimeter ditches. Fractured
      regression analyses show that 6 years after construction, P. australis invasion
      can be extensive. Linear regression analysis suggests that, if conditions remain
      favorable for P. australis colonization, constructed wetlands could be overrun in
      40 years. KEY WORDS: Phragmites australis; Mitigation; Constructed wetlands;
      Invasive species; Global positioning system

PMID- 9175547
TI  - Conceptual Design of a System for Selecting Appropriate Groundwater Models in
      Groundwater Protection Programs
AB  - / An effective groundwater protection program requires understanding of water
      flow and contaminant transport processes in the subsurface. Although many
      mathematical models have been developed to simulate the processes, few actually
      are used in groundwater protection programs due to the difficulties in data
      collection, model selection, and model implementation. This study presents a
      conceptual design of a GIS-supported model selection system that evaluates
      available data and mathematical models to facilitate groundwater protection
      programs. Steady-state groundwater and contaminant transport models applied in
      isotropic aquifers are placed into four classes to simulate conservative or
      nonconservative contaminant transports in simple or complex geohydrological
      conditions. After analyzing specific study objectives, available data, and model
      requirements, the proposed system selects a class of models that can be used in
      simulation and recommends any need for additional data collection. This study
      initiates an effort to integrate GIS, mathematical models, and expert knowledge
      in one system to promote the application of appropriate groundwater models. The
      new technology of GIS and digital data-base management makes it possible to
      develop such a system in practice.KEY WORDS: Groundwater models; Geographic
      information systems

PMID- 9175548
TI  - Germination, Growth, and Nodulation of Sesbania rostrata Grown in Pb/Zn Mine
      Tailings
AB  - / This study examined the possibility of growth, nodulation, and nitrogen
      accumulation of Sesbania rostrata in pure and amended Pb/Zn tailings. About 90%
      of seeds of S. rostrata germinated in pure Pb/Zn tailings, which contained high
      concentrations of Pb, Zn, Cu, and Cd. Although seedling growth suffered from the
      adverse environment of Pb/Zn tailings, they became established on tailings
      stands, in the greenhouse, as well as on the actual tailings dam, and completed
      their life cycle in 4 months. Dry matter production and nitrogen accumulation was
      3200 kg/ha and 69.4 kg/ha, respectively in the actual tailings dam. Applying
      inorganic fertilizer to Pb/Zn tailings led to no obvious improvement in growth
      and nodulation of S. rostrata, while tailings amended by river sediment or
      domestic refuse rich in organic matter improved the growth and nodulation of the
      species. Azorhizobium caulinodans survived and formed N-fixing stem and root
      nodules in S. rostrata grown in pure Pb/Zn tailings with a nodule biomass
      exceeding 300 mg fresh matter per plant.KEY WORDS: Sesbania rostrata;
      Azorhizobium caulinodans; Pb/Zn mine tailings; Revegetation; Nitrogen fixation;
      Heavy metals; Tolerance

PMID- 9175549
TI  - Comparing Environmental Conditions Using Indicators of Pollution Hazard
AB  - / Land use/land cover classifications for 1973 and 1991, derived from the
      interpretation of satellite imagery, are quantified on the basis of biophysical
      land units in a study area in southeastern Australia. Nutrient export potentials
      are estimated for each land unit based on their composition of land use/land
      cover classes. Spatial and temporal comparisons are made of the land units based
      on the calculated pollution hazard indicators to provide an insight into changes
      in the state of the environment and the regional significance of land use
      changes. For example, one ecosystem, unique to the study, showed a large increase
      in pollution hazard over the study period as a manifestation of an 11-fold rise
      in cleared area and an expansion of cropping activities. The benefits to
      environmental management in general are discussed.KEY WORDS: Land cover change;
      Nutrient export; Environmental condition; Pollution hazard; Agricultural
      pollution; Nonpoint source pollution; Diffuse pollution; Environmental
      degradation

PMID- 9175550
TI  - ENVIRONMENTAL AUDITING: The Functional Unit in the Life Cycle Inventory Analysis
      of Degreasing Processes in the Metal-Processing Industry
AB  - / In 1986 degreasing processes in the German metal-processing industry
      contributed about 70,000 t to the emission of chlorinated C1 and C2 hydrocarbons
      (trichloroethane, trichloroethene, tetrachloroethene, dichloromethane). Measures
      aiming at the reduction of toxic emissions and ozone depletion potential (ODP)
      may possibly lead to a shift of environmental impacts towards higher energy
      consumption, emission of waste water, and volatile organic compounds (VOC) with
      photochemical oxidant creation potential (POCP). The present article concerns
      itself with a life cycle assessment of the three main degreasing processes in
      order to compare their integral environmental impacts with one another. This is
      supplemented by presenting the methodology of the life cycle inventory life cycle
      inventory analysis (LCI). Generally, the applicability of the established LCI
      method can be shown quite clearly. However, some difficulties arise, especially
      at the stage of the goal definition, as the use of the process and the functional
      unit cannot be pinned down as easily and neatly as for most other products. The
      definition of the use of the process and the functional unit is not as
      straightforward as for most products. Among the potential functional units
      identified are the mass of removed impurities, cleaning time, cleaning work,
      percentage of purity, throughput of parts, loads, mass or surface and virtual
      coefficients. The mass of removed impurities turned out to be the most suitable
      parameter for measuring the technical performance of degreasing processes. The
      article discusses background, purpose, scope, system boundaries, target group,
      process tree and representativeness of the present study.KEY WORDS: Functional
      unit; Life cycle assessment; Life cycle inventory analysis; Degreasing processes;
      Metal processing

PMID- 9175551
TI  - Characterization of a cry2A gene cloned from an isolate of Bacillus thuringiensis
      serovar sotto.
AB  - A cry2A-type gene, designated as cry2(SKW), was cloned from Bacillus
      thuringiensis serovar sotto SKW01-10.2-06, and some unique features of the gene
      were revealed. The cry2(SKW) gene encoded a polypeptide of 635 residues with a
      predicted molecular mass of 71,137 Da. Cry2(SKW) had 95.4% identity with Cry2Aa
      in amino acid sequence and was two residues longer than Cry2Aa. Two open reading
      frames (ORFs), designated as orf1 and orf2, were present upstream of the
      cry2(SKW) and showed high homology with the corresponding ORFs in the cry2Aa
      operon. The Orf2 from SKW01-10.2-06 contained a region of repeated sequences.
      However, unlike Cry2Aa, Cry2(SKW) formed the cuboidal crystalline inclusions when
      the cry2(SKW) gene was expressed in an acrystalliferous B. thuringiensis strain
      in the absence of the upstream ORFs. Furthermore, Cry2(SKW) was less toxic to a
      lepidopteran species, Bombyx mori, than Cry2Aa in spite of high homology between
      the two proteins.

PMID- 9175552
TI  - Snr, new genetic loci common to the nitrate reduction systems of Pseudomonas
      aeruginosa PAO1.
AB  - Pseudomonas aeruginosa is able to both assimilate and dissimilate nitrate. On the
      basis of the characteristics of mutants unable to dissimilate or assimilate
      nitrate to nitrite, it was revealed that two different sets of genes (represented
      by Class I and Class II mutants) were shared between the nitrate-to-nitrite
      reduction steps of both pathways. The genes represented by Class I and II mutants
      have been separated into distinct genetic loci using two cosmids, pAD1695/96. The
      two different genetic loci have been designated snr (shared nitrate reduction)
      and mol (MoCo processing genes) based on the phenotypic characteristics of the
      mutants complemented. Restriction analyses of pAD1695/96 followed by subcloning
      confirmed the complementation results. The snr loci, which represent a unique and
      hitherto uninvestigated set of genes for nitrate reduction, were mapped on the P.
      aeruginosa chromosome by linkage analysis with sex factor FP2.

PMID- 9175553
TI  - Lysine 194 is functional in isocitrate lyase from Escherichia coli.
AB  - Lysine 194 in conserved stretch 1 of tetrameric isocitrate lyase from Escherichia
      coli has been replaced by using the restriction-enzyme-site elimination method of
      directed mutagenesis. Expression of subunits of each variant and of wild-type
      (wt) enzyme was equivalent and all variants assembled into tetrameric proteins.
      The variants K194R and K194H had kcat values relative to that of wt enzyme taken
      as 100 of 11 and 7, respectively. Km values for Mg2+-Ds-isocitrate (in mM units)
      were: 0.13 for wt-enzyme; 0.12 for the K194R variant; and 0.55 for the K194H
      variant. Substitution at position 194 of Leu or Glu resulted in zero catalytic
      activity. These results establish that Lys 194 is another functional residue in
      conserved stretch one of isocitrate lyase from E. coli besides H184, K193, C195,
      and H197. Because K194 can be specifically replaced by the basic residues His and
      Arg with resultant lowered activity and by His with an increased Km value, it may
      contribute to a cation center and facilitate substrate binding as well as
      orientation of the developing transition state.

PMID- 9175555
TI  - Construction of a Fibrobacter succinogenes genomic map and demonstration of
      diversity at the genomic level.
AB  - The genomic cleavage map of the type strain Fibrobacter succinogenes S85 was
      constructed. The restriction enzymes AscI, AvrII, FseI, NotI, and SfiI generated
      DNA fragments of suitable size distribution that could be resolved by pulsed
      field gel electrophoresis (PFGE). An average genome size of 3.6 Mb was obtained
      by summing the total fragment sizes. The linkages between the 15 AscI fragments
      of the genome were determined by combining two approaches: isolation of linking
      clones and cross-hybridization of restriction fragments. The genome of F.
      succinogenes was found to be represented by the single circular DNA molecule.
      Southern hybridization with specific probes allowed the eight genetic markers to
      be located on the restriction map. The genome of this bacterium contains at least
      three rRNA operons. PFGE of the other three strains of F. succinogenes gave
      estimated genome sizes close to that of the type strain. However, RFLP patterns
      of these strains generated by AscI digestion are completely different. Pairwise
      comparison of the genomic fragment distribution between the type strain and the
      three isolates showed a similarity level in the region of 14.3% to 31.3%. No
      fragment common to all of these F. succinogenes strains could be detected by
      PFGE. A marked degree of genomic heterogeneity among members of this species
      makes genomic RFLP a highly discriminatory and useful molecular typing tool for
      population studies.

PMID- 9175556
TI  - Iron and salicylate induction of cytochrome P450BM-1 in Bacillus megaterium.
AB  - The effects of iron and salicylate on the expression of cytochrome P450s in
      Bacillus megaterium were investigated in this report. Immunoblot analysis showed
      that the addition of 4 mM ferric iron or 10 mM salicylate to the culture medium
      resulted in a significant increase in the P450BM-1 level, while the same
      condition had little effect on P450BM-3 expression. Substantial induction of
      chloramphenicol acetyltransferase (CAT) activity by iron and salicylate in B.
      megaterium cells bearing a P450BM-1 promoter-cat transcriptional fusion vector
      suggests that the induction of P450BM-1 by iron and salicylate occurs at the
      transcriptional level. Unexpectedly, in contrast to the bm1P1-dependent induction
      of P450BM-1 by pentobarbital, disruption of bm1P1 gene did not affect induction
      of P450BM-1 by iron and salicylate. This result suggests that the induction of
      P450BM-1 by iron and salicylate occurs by a bm1P1-independent mechanism. To our
      knowledge, this is the first example of an iron-regulated cytochrome P450 gene in
      prokaryotes.

PMID- 9175557
TI  - Purification and characterization of a cysteine protease produced by pathogenic
      luminous Vibrio harveyi.
AB  - The purification and characterization of an extracellular protease produced by
      pathogenic luminous Vibrio harveyi strain 820514, originally isolated from
      diseased tiger prawn (Penaeus monodon), was presented in this paper. The
      purification steps included ammonium sulfate precipitation, with columns of
      hydrophobic interaction chromatography and anion exchange on fast protein liquid
      chromatography. The protease is an alkaline cysteine protease, heat labile,
      inhibited by iodoacetamide, iodoacetic acid, N-ethylmaleimide, p
      chloromercuribenzoate, and p-chloromercuribenzene-sulfonic acid, and showed
      maximal activities at pH 8 and 50 degrees C, having a molecular mass of 38 kDa as
      estimated by SDS-PAGE and gel filtration column. In addition, the protease was
      also completely inhibited by CuCl2 and HgCl2, but not or only partially inhibited
      by other inhibitors tested. Furthermore, 2-mercaptoethanol was the most effective
      reducing agent in the activation of the enzyme. The present protease is the first
      cysteine protease found in Vibrio species.

PMID- 9175558
TI  - Investigation of mosquito-specific larvicidal activity of a soil isolate of
      Bacillus thuringiensis serovar canadensis.
AB  - The LC50 value of alkali-solubilized parasporal inclusion proteins of a Diptera
      specific strain, belonging to Bacillus thuringiensis serovar canadensis, was 2.4
      microg/ml for larvae of the mosquito, Aedes aegypti. A significant loss in
      larvicidal activity occurred when solubilized inclusion proteins were treated
      with A. aegypti larval gut extract, silkworm (Bombyx mori) larval gut juice, and
      the proteinase K. Approximately 90% of the larvicidal activity was destroyed upon
      treatment with proteases in 30 min. The parasporal inclusion was composed of
      major proteins of 65, 53, and 28 kDa and some other minor proteins. Proteolysis
      profiles showed that the 65-kDa major protein is highly sensitive to proteases.
      Purification experiments with DEAE-Toyopearl column chromatography revealed that
      the 65-kDa protein is responsible for the mosquitocidal activity of this strain.
      The LC50 value of the purified protein was 5.4 microg/ml.

PMID- 9175559
TI  - Competition between ruminal cellulolytic bacteria for adhesion to cellulose.
AB  - Competition for adhesion to cellulose among the three main ruminal cellulolytic
      bacterial species was studied using differential radiolabeling (14C/3H) of cells.
      When added simultaneously to cellulose, Ruminococcus flavefaciens FD1 and
      Fibrobacter succinogenes S85 showed some competition; however, both species were
      surpassed competitively by Ruminococcus albus 20. When R. flavefaciens FD1 and F.
      succinogenes S85 were already adherent, R. albus 20 adhesion occurred without
      inhibition but involved R. flavefaciens FD1 detachment.

PMID- 9175560
TI  - Purification and characteristics of an autolytic chitinase of Piromyces communis
      OTS1 from culture medium.
AB  - An autolysis chitinase was purified from the cultural medium of the anaerobic
      fungus Piromyces communis OTS1 by ammonium sulfate precipitation, affinity
      chromatography with regenerated chitin, chromato-focusing, gel filtration, and
      chromato-focusing again. The optimal pH and temperature were 6.0 and 50 degrees
      C, respectively, for a 20-min assay. The chitinase was stable from pH 6.0 to 8.0,
      but was unstable at 70 degrees C for 20 min. The molecular mass of chitinase was
      estimated by SDS-PAGE to be 44.9 kDa, and its pI was 4.4. The enzyme activity,
      which was of the 'endo' type, was inhibited by Hg2+ and allosamidin. The
      chitinase hydrolyzes chitin powder and fungal cell walls at a higher rate than an
      artificial chitin substrate. It can be concluded that extracellular chitinase is
      similar to cytosolic chitinase, but they are not the same protein.

PMID- 9175562
TI  - Identification of a cold shock gene in lactic acid bacteria and the effect of
      cold shock on cryotolerance.
AB  - When Lactic Acid Bacterial cultures were frozen at -20 degrees C for 24 h, the
      cell viability decreased drastically, but when they were cold shocked at 10
      degrees C for 2 h prior to freezing, viability improved significantly for the
      Lactococcus lactis subsp. lactis strains (25-37%) and Pediococcus pentosaceus PO2
      (18%), but not for the Lactococcus lactis subsp. cremoris strains tested or for
      one strain of Lactobacillus helveticus LB1 and Streptococcus thermophilus TS2.
      When the period for cold shock was extended to 5 h, the viability increased even
      further for those strains that displayed cold shock cryotolerance. Use of
      degenerate PCR primers based on the major cold shock protein (csp) of both
      Escherichia coli and Bacillus subtilis resulted in PCR products from all strains
      tested. The PCR product from Lactococcus lactis ssp. lactis M474 was cloned and
      sequenced, and the deduced amino acid sequence displayed a high sequence
      similarity to other csp's. Use of PCR primers based on the M474 sequence resulted
      in PCR products being produced only from the lactococcal strains studied and not
      from the Lactobacillus helveticus, Streptococcus thermophilus, or Pediococcus
      pentosaceus strains tested.

PMID- 9175563
TI  - Anaerobic phenol degradation by microorganisms of swine manure.
AB  - Swine manure contains diverse groups of aerobic and anaerobic bacteria. An
      anaerobic bacterial consortium containing sulfate-reducing bacteria (SRB) and
      acetate-utilizing methanogenic bacteria was isolated from swine manure. This
      consortium used phenol as its sole source of carbon and converted it to methane
      and CO2. The sulfate-reducing bacterial members of the consortium are the
      incomplete oxidizers, unable to carry out the terminal oxidation of organic
      substrates, leaving acetic acid as the end product. The methanogenic bacteria of
      the consortium converted the acetic acid to methane. When a methanogen inhibitor
      was used in the culture medium, phenol was converted to acetic acid by the SRB,
      but the acetic acid did not undergo further metabolism. On the other hand, when
      the growth of SRB in the consortium was suppressed with a specific SRB inhibitor,
      namely, molybdenum tetroxide, the phenol was not degraded. Thus, the metabolic
      activities of both the sulfate-reducing bacteria and the methanogenic bacteria
      were essential for complete degradation of phenol.

PMID- 9175565
TI  - The left atrium in hypertension, an appendage often forgotten.

PMID- 9175566
TI  - Changes in left ventricular mass during treatment with minoxidil and cilazapril
      in hypertensive patients with left ventricular hypertrophy.
AB  - Attainment of the regression of hypertension-associated left ventricular
      hypertrophy (LVH) seems to be a desirable goal of blood pressure (BP)-reducing
      therapy. Since antihypertensive drugs of differing types may exhibit markedly
      different abilities to modulate LVH, we examined the effects of the angiotensin
      converting enzyme inhibitor cilazapril, and the potassium channel activator
      minoxidil, alone or in combination with each other, on the left ventricular mass
      (LVM) in patients with severe essential hypertension who had LVH detected by
      echocardiography. All patients received the same base therapy of bopindolol and
      guanfacine. After a run-in period, they were treated with: (1) cilazapril (n =
      10); (2) minoxidil, combined with a diuretic (n = 10); or (3) both cilazapril and
      monoxidil (n = 6) for 12 months. The LVM index (LVMI; LVM per body surface area)
      was estimated every 3 months by means of echocardiography. Each kind of therapy
      decreased the arterial pressures to a similar degree. The 1-year treatment with
      the cilazapril-based regimen resulted in a significantly diminished LVMI (from a
      mean +/- s.d. of 173 +/- 38 to 152 +/- 22 g/m2; P < 0.05). On the other hand, the
      minoxidil-based therapy led to a significant increase in LVMI (from 148 +/- 19 to
      170 +/- 35 g/m2; P < 0.05). There were no significant LVMI changes in patients
      receiving the combined, cilazapril + minoxidil-based treatment (172 +/- 34 vs the
      pretreatment 183 +/- 54 g/m2). The results confirm that long-term treatment with
      cilazapril is effective both in reducing BP and in reducing LVM. In spite of
      yielding a satisfactory reduction of BP, minoxidil therapy, even in combination
      with a diuretic and a beta-blocker, may lead to an aggravation of pre-existing
      LVH; this effect of minoxidil could be prevented by the simultaneous
      administration of cilazapril.

PMID- 9175567
TI  - Plasma catecholamines in pre- and in postmenopausal women with mild to moderate
      essential hypertension.
AB  - The sympathetic nervous system (SNS) is thought to play an important role in the
      pathogenesis of essential hypertension and many studies have established a
      relationship between plasma levels of norepinephrine (NE) and epinephrine (E) and
      sympathetic nervous activity (SNA). Furthermore, it has been suggested that
      climacteric women are more exposed to psychosocial stress which can produce a
      transient rise in blood pressure (BP) and, with time, determine a hypertensive
      state. Plasma NE and E levels were measured at rest and after physiological
      stimulation (head-up tilt test) in 20 hypertensive (BP: 146 +/- 13/101 +/- 4 mm
      Hg) and in 20 normotensive women (BP: 132 +/- 7/85 +/- 4 mm Hg). Women in each of
      these two groups were further subdivided according to their climacteric status
      (10 premenopausal and 10 postmenopausal women). No difference in NE values at
      rest was found between groups and subgroups. During head-up tilt test, Ln NE
      plasma values increased in normotensive and hypertensive groups; the rise was
      significantly higher in hypertensive than in normotensive women (P < 0.01). In
      climacteric subgroups, Ln NE appeared markedly increased above resting levels in
      pre- and postmenopausal hypertensive women when their position was changed from
      supine to upright (P < 0.01). Since high plasma NE levels after stimulation (head
      up tilt) are associated with sympathetic overactivity, we conclude that SNA is
      involved in the pathogenesis of essential hypertension in climacteric women.

PMID- 9175568
TI  - Evaluation of the Critikon 8100 and Spacelabs 90207 non-invasive blood pressure
      monitors using a test simulator.
AB  - The Critikon Dinamap 8100 and the Spacelabs 90207 ambulatory non-invasive blood
      pressure (NIBP) monitors were evaluated using a test simulator using an
      evaluation protocol which covered a wide range of simulated pressures (with five
      determinations at each of six steps from 60/30 to 200/150 mm Hg), pulse rates
      (from 40 to 200 bpm), artefact levels (simulated motion and tremor artefact) and
      pulse strengths (down to 10% of the nominal strength). Determinations were made
      at 5 min intervals. The average and standard deviation of the five measurements
      at each condition were calculated. The Spacelabs recorded pressures with a
      greater consistency than the Dinamap which showed a higher standard deviation
      under all the conditions. The relatively high standard deviation of the
      recordings made by the Dinamap could explain the non-systematic errors found in
      some evaluations. Both instruments recorded pressures within 5 mm Hg of the
      target over the range of pressures and pulse rates, and coped well under
      conditions of severe artefact and weak pulsations, either by signalling inability
      to record or by recording satisfactorily.

PMID- 9175569
TI  - Relationship between self-perceived stress and blood pressure.
AB  - OBJECTIVE: The importance of stress in the pathogenesis of essential hypertension
      is controversial. In this study we wanted to evaluate the relation between self
      perceived stress and the blood pressure (BP) in a asymptomatic healthy
      population. SUBJECTS AND METHODS: A total of 1666 guests (mean +/- s.d. age 50 +/
      16 years) attending the air show AIR94 in Buochs, Switzerland volunteered to
      participate in a cross-sectional study. Using a self-administered questionnaire
      and visual analogue scales the individual stress perception and other
      cardiovascular risk behaviours/factors were assessed. BP, body weight, height,
      and the waist:hip ratio were measured. RESULTS: Individual stress perception was
      inversely related with the systolic BP (SBP) (r = -0.12, P < 0.001). The
      relationship was found in both men and women and was independent of age and/or
      body weight. No relation was found between the diastolic BP (DBP) and stress
      perception. Subjects with high normal BP according the JNC V classification
      showed a lower stress perception than did subjects with normal BP. In a multiple
      regression model the stress score was fourth most predictive of the SBP after
      body mass index, waist:hip ratio, and age followed by alcohol and fat intake.
      CONCLUSION: In this study we found an inverse association between the self
      perceived stress and SBP. We suggest that the inverse association between BP and
      the self-perceived stress reflects a neuroendocrine and biochemical setting
      characterized by inadequate stress handling associated with a higher fat and
      alcohol intake and more abdominal fat tissue leading to a higher BP. Our data
      suggest that stress denial in combination with abdominal obesity, alcohol
      consumption, and smoking may be proxy for a high stress level.

PMID- 9175570
TI  - Impact of the renin-angiotensin-aldosterone system on blood pressure response to
      intravenous enalaprilat in patients with hypertensive crises.
AB  - The purpose of the study was to evalute the impact of the renin-angiotensin
      aldosterone (RAA) system on blood pressure (BP) response in patients with
      hypertensive emergencies and urgencies treated with intravenous enalaprilat.
      Thirty-five patients with a systolic BP (SBP) >210 mm Hg and/or diastolic BP
      (DBP) >110 mm Hg received 5 mg enalaprilat intravenously. The extent of systolic
      and DBP reduction was correlated with pretreatment concentrations of angiotensin
      II (ANGII) (SBP: r = -0.47; P = 0.006; DBP: r = -0.55; P = 0.001) and plasma
      renin activity (PRA) (SBP: r = -0.49; P = 0.003; DBP: r = 0.48; P = 0.007). Non
      responders to enalaprilat exhibited significant lower pretreatment levels of PRA,
      angiotensin-converting enzyme (ACE) and ANG II compared to responders (PRA: 5.5
      +/- 3.7 vs 1.1 +/- 2.2 ng/ml/h, P < 0.001; ACE: 12.8 +/- 3.5 vs 8.2 +/- 4.8 U/l,
      P = 0.003; ANG 11:8.7 +/- 6.2 vs 5.0 +/- 3.8 pg/ml, P = 0.04). In patients with
      severe hypotension following application of enalaprilat ANG II concentrations
      were significantly higher compared to patients with mean arterial BP reduction
      <25% (12.3 +/- 6.7 vs 5.6 +/- 4.0 pg/ml,P = 0.013). These data indicate that PRA
      and ANG II are the major determinants for BP response to enalaprilat. This
      relation between BP response and RAA system activity have important clinical
      implications for the treatment of patients with severe hypertension. Primary
      therapeutic failure indicates that the RAA system contributes very little to the
      hypertensive status of the patient. Thus, repetitive application on an ACE
      inhibitor in primary responders is clinically unhelpful and may result in an
      unnecessary delay of an effective BP reduction. In contrast, high ANG II
      concentrations are associated with a considerable risk for severe hypotension
      after enolanalaprilat application. Therefore, the status of the RAA system
      determines the efficacy as well as the safety of ACE inhibitor treatment in
      patients with severe hypertension.

PMID- 9175571
TI  - Identification and management of stroke risk in older people: a national survey
      of current practice in primary care.
AB  - The current practice of stroke prevention was assessed among UK general
      practitioners (GPs) using a postal questionnaire. A random sample of 583 GPs
      (response rate 60%) in practice throughout the UK was examined. Main outcomes
      were the reported practice in the identification of stroke risk, management of
      hypertension, and use of other interventions (particularly aspirin treatment) to
      reduce the risk of stroke. Most respondents (451, 77%) reported that they
      specifically identified patients at high risk of stroke. However, of these only
      301 (67%) used more than one major risk factor to do this and less than one-third
      used either age or pre-existing cardiovascular disease as an indicator.
      Thresholds for drug treatment of hypertension increased markedly with patient age
      with only 68%, 23% and 9% of respondents reporting treating elevated systolic,
      diastolic and isolated systolic pressures respectively, in accord with the
      British Hypertension Society (BHS) guidelines for patients aged 70-79 years.
      Thresholds for blood pressure (BP) treatment in older patients did not differ by
      region but were higher among respondents who had been in general practice for
      more than 10 years. The value of aspirin in preventing stroke in patients with
      pre-existing cardiovascular disease was recognized by almost all (560, 96%)
      respondents. The results suggest that there is scope for increasing the benefits
      of stroke prevention in primary care, by focusing on the management of patients
      at high absolute risk, in whom the greatest treatment benefits are likely to be
      obtained.

PMID- 9175572
TI  - Defining hypertension in older people from primary care case notes review.
AB  - A method of defining blood pressure (BP) status from a review of primary care
      patient records was developed and then validated using the case notes of a
      general practitioner with an interest in hypertension. Data were drawn from the
      records of the previous 6 years of all 65 to 80-year-old patients in the practice
      (n = 263). Patients were then categorised as hypertensive, normotensive or
      'undetermined' by using a flowchart based on the mean of the three most recent BP
      measurements, antihypertensive medication and comorbidities of ischaemic heart
      disease, myocardial infarction, angina, oedema or cardiac failure. Mean systolic
      BP of > or = 160 mm Hg and/or diastolic BP of > or = 90 mm Hg were used as a
      threshold definition of hypertension and of BP control. Disagreement between
      general practitioner and the notes based definition occurred in 11% of patients
      (5% hypertensive, 6% normotensive). Reasons for disagreement were: controlled
      hypertensives with comorbidities such as angina or heart failure (4%), isolated
      elevated readings (3%), use of antihypertensive medication for separate
      indications (2%), other reasons (2%). The resulting sensitivity and specificity
      was 86% and 88% respectively. Including the recording of a diagnosis of
      hypertension in the definition increased the sensitivity to 98% with specificity
      unchanged at 88%. Actual sensitivity of the instrument when used in other
      practices is likely to lie between 88% and 98% depending on the quality of the
      doctor's recording of the diagnosis of hypertension. These findings suggest that
      data from primary care case notes can provide a ready and valid means of defining
      cases of hypertension for studying the management of hypertension in primary care
      and for research purposes.

PMID- 9175573
TI  - Attitudes to adverse drug reaction reporting by medical practitioners in a
      Northern Italian district.
AB  - Attitudes to adverse drug reaction (ADR) spontaneous reporting were investigated
      among all the National Health Service (NHS) doctors operating in the territory of
      the Area Health Authority n.1 of Varese (Italy), to assess their awareness of the
      reporting system and to identify reasons for under reporting. Three hundred and
      fifty doctors were sent questionnaires and 207 (59.1%) were returned completed.
      More than 77% of the responders stated to have noticed ADRs, which were mainly
      reported to the pharmaceutical manufacturers and, in a minority of cases, to the
      NHS. Fifty per cent did not report ADRs to anyone. Important factors for deciding
      to report were unusualness and severity of the reaction, and involvement of a new
      drug. The main reason for not reporting was the clinical negligibility of the
      reaction. There was little knowledge about the types of reactions to be
      preferentially reported and the purposes of ADR reporting systems. Nevertheless,
      nearly everyone asked for feed-back information about reported ADRs. NHS doctors
      in this district have little information concerning ADR reporting systems. Some
      effective measures to improve the situation could be: inclusion of
      pharmacovigilance into pre- and post-graduated continuing education programs,
      provision of guidelines for ADR spontaneous reporting and of feed-back
      information to reporters, implementation of regional pharmacovigilance units.

PMID- 9175574
TI  - Drugs trying to get the parents: there will be incentives for the European
      scientific community to develop research in the field of the orphan drugs.

PMID- 9175575
TI  - Senescence, immortalization and cancer.

PMID- 9175576
TI  - Binding of methamphetamine to serum albumin in various species in vitro.
AB  - While drugs from experimental animals provide very important information, it is
      also true that data differ from species to species, and that data from
      experimental animals cannot be applied directly to humans. The binding parameters
      of serum albumin from various animal species and methamphetamine were
      investigated in vitro by the Scatchard method. The Scatchard plots for the
      binding of serum albumin and methamphetamine were classified into three patterns:
      straight lines for human and rat serum albumin; downwardly convex curves for
      bovine and rabbit serum albumin; and upwardly convex curves for horse, mouse and
      chicken serum albumin. Hill coefficients were calculated for binding in which the
      Scatchard plots were upwardly convex curves and for guinea pig serum albumin. The
      results suggested the existence of positive cooperativity between the
      methamphetamine binding sites on serum albumin from the horse, mouse, chicken and
      guinea pig. Furthermore, the process of methamphetamine binding to human serum
      albumin appears to differ from the process for all experimental animals except
      the rat, and there are also differences between the binding processes in the
      various experimental animals.

PMID- 9175577
TI  - Sex- or age-related differences were not detected in the activity of
      dihydropyrimidine dehydrogenase from rat liver.
AB  - We examined the influence of ageing and gender on the activity of
      dihydropyrimidine dehydrogenase (DPD) in male and female Sprague-Dawley rats at
      3, 8, 40 and older than 60 weeks of age. The body and liver weights of male rats
      at 8 weeks and older of age were heavier than those of female rats at the same
      age and the ratio of liver to body weight was significantly reduced with ageing.
      The amount of produced 5FU metabolites, dihydrofluorouracil and
      fluoroureidopropionic acid, remained unchanged in the reaction mixture with the
      cytosol from any group of the rats. The formation rates of 5FU metabolite were
      1.03+/-0.08/1.12+/-0.06, 0.98+/-0.11/1.16+/-0.10, 1.13+/-0.09/1.13+/-0.11 and
      1.17+/-0.16/1.24+/-0.08 nmol min(-1) mg protein(-1) (mean+/-SD, male/female) in
      rats at 3, 8, 40 and older than 60 weeks of age, respectively. The results
      suggest that the DPD activity in the rat liver may not be affected by ageing or
      gender.

PMID- 9175578
TI  - Modification of reproductive function in the rat by 3-methylcholanthrene.
AB  - Repeated exposure of adult female Wistar rats to 3-methylcholanthrene (MC) (25 mg
      kg(-1) b.w., i.p., 2xwk, 1 mo) was associated with a significant increase in
      estrus cycle length. In addition, an increased frequency of females with constant
      diestrus and abnormal cycles was observed. Young females which had been exposed
      to MC prepubertally or whose parents had been treated with MC before and during
      mating also demonstrated cycle prolongation and an increased incidence of
      constant diestrus and abnormal cycles. These changes in female reproductive
      function were not associated with measurable changes in plasma sex hormone
      levels. In contrast, MC exposure in adult males was associated with significant
      reductions in circulating plasma testosterone levels. The present data also
      suggest that the offspring of parents who had been exposed repeatedly to MC
      before and during mating are also affected. Although the central nervous system
      in offspring of MC-treated parents appeared to be intact, their oral body
      temperature was significantly lower.

PMID- 9175579
TI  - Actions of moguisteine on cough and pulmonary rapidly adapting receptor activity
      in the guinea pig.
AB  - With anaesthetized guinea pigs, the actions of moguisteine were tested on the
      cough reflex, the resting discharge of lung rapidly adapting receptors (RARs),
      RAR activity induced by aerosols of capsaicin, stimulation of RARs due to i.v.
      injection of capsaicin, and on the reflex responses to i.v. capsaicin. I.v.
      moguisteine (20 microg kg(-1)), compared with vehicle, decreased the spontaneous
      firing of RARs. Intragastric (i.g.) moguisteine (200 mg kg(-1)) had no effect on
      resting discharge. I.g. moguisteine depressed the cough response due to capsaicin
      aerosol (0.01(-1) mg ml(-1)) and significantly reduced the increased discharge of
      the RARs due to the aerosol. I.v. and i.g. moguisteine reduced the proportionate
      increase in RAR discharge due to i.v. capsaicin (50 microg kg(-1)). It did not
      appreciably affect the cardiovascular and respiratory responses to i.v.
      capsaicin, which presumably activated lung C-fibre receptors. We conclude that
      the antitussive action of moguisteine is mediated at least in part by a decrease
      in the excitatory response of RARs to tussive stimuli.

PMID- 9175580
TI  - L-histidine/medroxyprogesterone acetate interaction modulates human breast cancer
      cell growth and progestin receptor expression in vitro.
AB  - The effect of different L-histidine concentrations on human mammary tumour cell
      (CG5) proliferation was studied to test the hypothesis of a role of histidine in
      modulating sex steroid-regulated cell proliferation. Cell growth was only
      possible in the 10(-5) M and 10(-2) M range, while its inhibition by
      medroxyprogesterone acetate was confined to the 10(-4) M and 10(-3) M range. 10(
      3) M L-histidine enhanced the effect of medroxyprogesterone acetate in reducing
      the number of cells in the S phase. The results show also that 10(-3) M L
      histidine favours progestin diffusion into cells and increases progestin
      receptors density. The present data are in line with previous observations of the
      effect of histidine on the growth of experimental animal tumours, add evidence
      that histidine concentration influences the control of cell proliferation by sex
      steroids, and suggest a possible use of histidine in association with
      progestational drugs in the treatment of human neoplasia.

PMID- 9175581
TI  - Prolonged exposure to 5'-N-ethylcarboxamidoadenosine (NECA) does not affect the
      adenosine A2A-mediated vasodilation in porcine coronary arteries.
AB  - At present, four distinct adenosine receptors (A1, A2A, A2B, and A3) have been
      cloned and characterized in several species. It is known that prolonged exposure
      of tissues to receptor agonists induces A1 receptor desensitization. However,
      controversial data are reported on whether or not prolonged stimulation of A2A
      adenosine receptors induces tolerance. Using the porcine coronary artery, a
      sensitive vascular model, studies were designed, with the aim to clarify how
      prolonged exposure to the adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA)
      affects A2A receptor responsiveness. The arteries were precontracted with
      PGF2alpha (3 microM) and cumulative dose-response curves to either NECA itself,
      or the selective A2A agonists, 2-[4-2(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamidoadenosi ne (CGS 21680) and 2-hexynyl-5'-N
      ethylcarboxamidoadenosine (2HE-NECA) were obtained. In separate experiments,
      coronary rings were incubated with NECA (10 microM) for 30 min or 2 h. After 2 h
      washout period, functional response was assessed. The arteries showed high
      sensitivity to adenosine agonist-induced vasorelaxation. EC50 (nM) values were
      71.8 (35.5-145), 20.0 (11.2-32.7) and 40.2 (20.4-79.1) for NECA, 2HE-NECA and CGS
      21680, respectively. Vasorelaxant response of A2A selective agonists 2HE-NECA and
      CGS 21680 was not influenced by preincubation with NECA for 30 min or 2 h.
      Conversely, dose-response curves to NECA were shifted toward the right by
      preincubation with NECA itself: ED50 (nM) values were 114 (79.2-165), 211 (161
      276) and 412 (132-1290) for 30 min, 2 h and 15 h preincubation, respectively.
      These effects did not occur after 4 h washout. The present results indicate that
      prolonged stimulation of A2A receptors does not lead to loss of functional
      response, suggesting that this receptor subtype does not desensitize after
      prolonged stimulation by agonists.

PMID- 9175582
TI  - In-vitro testicular bioactivation of acrylonitrile.
AB  - The present work examines the mechanism of testicular toxicity of acrylonitrile.
      In testicular centrifugal fractions from Sprague Dawley rats, the metabolism of
      VCN to cyanide (CN-) was highest in the microsomal fraction and required NADPH
      for maximum activity. This biotransformation of VCN to CN- was characterized with
      respect to time (30 min), microsomal protein concentration (1.5 mg ml(-1)), pH
      (7.5) and temperature (37 degrees C). The V(max) of the reaction was 65.1 pmol CN
      mg protein(-1) min(-1) and K(m) was 88.6 micromol VCN. Flushing the microsomes
      with carbon monoxide (CO)(4:1, CO/O2 v/v), addition of benzimidazole (1 mM) or
      addition of SKF 525-A (5x10(-4) M) to incubation mixtures significantly inhibited
      VCN metabolism by 49%, 54% and 37.4% respectively. Activation of VCN to CN- was
      markedly increased in microsomes obtained from phenobarbital (PB)-treated rats
      (128.2%). Addition of glutathione (GSH), L-cysteine, D-penicillamine or 2
      mercaptoethanol significantly enhanced the release of CN- from VCN 126%, 247%,
      202% and 129% of the control value respectively. These findings indicate that VCN
      is metabolized in the testis via cytochrome P-450 dependent mixed function
      oxidase system.

PMID- 9175583
TI  - Cytokine-induced expression of CD1b molecules by peripheral blood monocytes:
      influence of 3'-azido-3'-deoxythymidine.
AB  - CD1b is a nonpolymorphic, MHC-like molecule, capable of presenting non-peptide
      antigens (Ags) to CD3+, CD4-, CD8-, alphabeta or gammadelta T lymphocytes.
      Previous studies have shown that CD1b can be induced in monocytes/macrophages by
      GM-CSF+IL-4, and can restrict their presentation of Mycobacterium tuberculosis
      antigen (Ag) to Ag-specific T cells. Since a number of HIV-positive subjects
      undergo mycobacterial infections, preliminary studies have been performed to
      explore whether anti-HIV chemotherapy would influence cytokine-induced CD1b
      expression in peripheral blood monocytes. The results obtained by treating
      monocytes with GM-CSF+IL-4, in presence or absence of 3'-azido-3'-deoxythymidine
      (AZT) showed that: (a) the majority of adherent mononuclear cells (AMNC)
      collected from peripheral blood of healthy donors, express CD1b molecule on the
      cell membrane, upon treatment with GM-CSF+IL-4; (b) CD1b appearance is mainly due
      to the de novo induction of CD1b gene expression (as confirmed by Northern blot
      analysis), rather than to migration of the molecule from the cytoplasm to the
      plasma membrane (as suggested by Western blot analysis); (c) AZT does not alter
      the percentage of CD1b+ AMNC treated with the cytokines; (d) however, AZT
      inhibits cytokine-induced proliferation of AMNC, thus reducing the overall Ag
      presenting potential of the host. Our results suggest that the anti-proliferative
      effect of AZT could depress anti-mycobacteria immunity in AZT-treated subjects,
      which may have important implication for the clinical outcome of patients
      harbouring inadequately treated mycobacterial infections.

PMID- 9175585
TI  - Arachidonic acid inhibits 3H-glutamate uptake with different potencies in rodent
      central nervous system regions expressing different transporter subtypes.
AB  - High-affinity glutamate reuptake in neurons and glial cells, a mechanism involved
      in the maintenance of physiological excitatory amino acid neurotransmission, can
      be inhibited by arachidonic acid (AA). We studied the effect of different doses
      (from 10 to 500 microM) of AA on L-[3H]glutamate uptake in synaptosomes from rat
      cortex, rat cerebellum and mouse spinal cord. We found that AA inhibition was
      dose-dependent, but the IC50 in the cortex differed significantly from those in
      the cerebellum and spinal cord (170+/-7.9 microM vs 42.5+/-5.4 microM and 34.7+/
      2.2 microM respectively). We therefore suggest that arachidonic acid modulates
      uptake differently in relation to the regional expression of the glutamate
      transporter subtypes.

PMID- 9175584
TI  - Antinociception induced by SM 32 depends on a central cholinergic mechanism.
AB  - The antinociceptive effect of SM 32 was examined in mice by using the hot-plate
      (10-40 mg kg(-1) i.p; 3-30 microg per mouse i.c.v.) and abdominal constriction
      (10-30 mg kg(-1) i.p) tests. In the antinociceptive dose-range, SM 32 did not
      impair mouse spontaneous motility and motor coordination evaluated respectively
      by the Animex and rota-rod tests. The increase in the pain threshold produced by
      SM 32 was prevented by dicyclomine, pirenzepine and hemicholinium-3 but not by
      naloxone and CGP 35348. In vitro experiments showed that the SM 32 amplified
      electrically- and nicotine-evoked guinea-pig ileum contractions. On the basis of
      the above data, it can be postulated that SM 32 exerts its antinociceptive effect
      through a potentiation of central cholinergic transmission.

PMID- 9175586
TI  - Biochemical basis of sodium valproate hepatotoxicity and renal tubular disorder:
      time dependence of peroxidative injury.
AB  - Mice fed with sodium valproate for 7, 14 and 21 days were evaluated for
      hepatotoxicity and renal tubular disorder. The drug was administered as an
      aqueous solution with an increasing concentration up to five days gradually
      reaching up to 0.71% w/v, which persisted throughout the study period. Mice fed
      with sodium valproate for 7, 14 and 21 days showed, marked hepatic injury and
      renal tubular disorder, evidenced by increased levels of malondialdehyde as a
      measure of lipid peroxidation. Administration of sodium valproate affected the
      glutathione contents both in liver and kidney tissue at all the three time
      points. However, this reduction in glutathione concentration was more pronounced
      in kidney when compared to control group. These results support the hypothesis
      that lipid peroxidation mediates the effect of sodium valproate on liver and
      kidney. Furthermore, the valproate induced toxicity is time related and the
      increase in lipid peroxide levels and depletion of glutathione occur time
      dependent even if the dose is clinically appropriate.

PMID- 9175587
TI  - Angiotensin II (3-8) induces long-term memory improvement in the crab
      Chasmagnathus.
AB  - A shadow moving overhead acts as a danger stimulus and elicits an escape response
      in the crab Chasmagnathus that habituates after 15 trials and for a long period
      of time. Previous work showed that angiotensin II enhances this long-term memory.
      Present results indicate: (1) that the facilitatory effect of angiotensin II is
      not blocked by either losartan, DUP 753 or the Parke Davis compound PD 123177;
      (2) that the angiotensin II (3-8) fragment has an enhancing effect on crab's
      memory stronger than that reported for the integer octopeptide; (3) that the
      hypermnestic effect of angiotensin II (3-8) is dose-dependent and saralasin
      reversible. The possibility that the action of angiotensin II on crab's memory
      were not due to its own action but to that of the degradation fragment
      angiotensin II (3-8) is discussed.

PMID- 9175588
TI  - Distinct soluble astrocytic factors induce expression of outward K+ currents and
      ramification of brain macrophages.
AB  - Isolated cultured murine brain macrophages (BM) were treated with supernatants of
      enriched astrocytic cultures. The astrocyte-conditioned medium (ACM) induced
      ramification of BM. In parallel, BM expressed voltage-gated outward K+ currents
      (I(K)) during the first 2 days after the application of ACM. However, in ramified
      BM which were treated once with ACM, I(K) disappeared 5 days after that
      treatment. In contrast, BM expressed I(K) over a period of more than 5 days when
      cells were treated daily with ACM. A blockade of I(K) by charybdotoxin or by
      kaliotoxin did not inhibit ramification of the cells. Furthermore, after
      application of low-concentrated ACM BM exhibited I(K) but did not change their
      morphology. It is suggested that in murine BM the ramification and the expression
      of I(K) are induced by distinct soluble factors derived from astrocytes.

PMID- 9175589
TI  - Electroconvulsive treatment evokes release of preprotachykinin-A mRNA into the
      cerebrospinal fluid and ocular aqueous humor of rabbits.
AB  - Following electroconvulsive treatment (ECT) of rabbits, preprotachykinin-A (PPT
      A) mRNA was detected by Southern blot analysis of polymerase chain reaction (PCR)
      amplified products in the cerebrospinal fluid (CSF) and aqueous humor of the eye.
      In contrast, no PPT-A mRNA could be detected in samples from untreated animals.
      In addition, several neuropeptides (substance P, neuropeptide Y, cholecystokinin,
      calcitonin gene-related peptide and pituitary adenylate cyclase activating
      peptide) were released into the CSF (and aqueous humor) following ECT. The
      results suggest that PPT-A mRNA was released together with neuropeptides into the
      CSF and aqueous humor in response to ECT. Indeed, previous studies have suggested
      that neurons can release neuropeptide mRNAs and that neurons are capable of
      taking up and expressing foreign mRNA. If neuropeptide mRNA can be taken up and
      utilized by another neuronal population, it might explain instances when neurons
      display 'phenotypic switch', i.e. the transient expression of novel
      neuropeptides.

PMID- 9175590
TI  - Enhanced binding of advanced glycation endproducts (AGE) by the ApoE4 isoform
      links the mechanism of plaque deposition in Alzheimer's disease.
AB  - Alzheimer's disease (AD) brains contain high levels of advanced glycation
      endproducts (AGEs). Double immunostaining using anti-AGE and anti-apolipoprotein
      E (apoE) antibodies demonstrated that AGEs co-localized to a very high degree
      with apoE. We examined the binding of apoE to in vitro-prepared AGE-bovine serum
      albumin (AGE-BSA), using Western ligand blot analysis. ApoE exhibited AGE
      specific binding activity in the presence of excess native BSA, with the dimeric
      form of apoE binding better than the monomeric form. Other apolipoproteins
      including apo A1, B, CI and CII, and serum beta2-microglobulin, did not bind AGE
      BSA. ApoE4 exhibited a 3-fold greater AGE-binding activity than the apoE3
      isoform. These results suggest that apoE may participate in aggregate formation
      in the AD brain by binding to AGE-modified plaque components. It is possible that
      enhanced binding of apoE4 might have pathogenic consequences in vivo.

PMID- 9175591
TI  - delta9-Tetrahydrocannabinol excites rat VTA dopamine neurons through activation
      of cannabinoid CB1 but not opioid receptors.
AB  - Behavioral, biochemical and recent electrophysiological data have increasingly
      implicated the involvement of dopamine in the central actions of cannabinoid
      compounds. However, the site and mechanism by which cannabinoids stimulate
      dopamine systems has been somewhat controversial. Central opioid systems have
      also been suggested to play a role in some cannabinoid-induced behaviors as
      evidenced by their attenuation in the presence of the opioid antagonist naloxone.
      However, recent studies using the cannabinoid receptor-selective antagonist
      SR141716A suggest that the central actions of psychoactive cannabinoids are
      mediated principally through activation of CB1 receptors. Using single cell
      electrophysiological recordings in the rat we assessed the effects of both
      SR141716A and naloxone on delta9-tetrahydrocannabinol (THC)-induced activation of
      ventral tegmental dopamine neurons. While dopamine cell firing was dose
      dependently increased following cumulative dosing with delta9-THC it was
      partially or completely inhibited following pretreatment with 0.5 and 2 mg/kg
      SR141716A, respectively. However, 1 and 10 mg/kg naloxone failed to alter the
      response to delta9-THC. These data provide the first evidence that delta9-THC
      induced changes in mesolimbic dopamine neuronal activity are mediated by the CB1
      cannabinoid receptor, but a causal link for the involvement of opioid systems
      could not be established.

PMID- 9175592
TI  - Blockade of pilocarpine- or kainate-induced mossy fiber sprouting by
      cycloheximide does not prevent subsequent epileptogenesis in rats.
AB  - Post-injury sprouting of hippocampal mossy fibers has been suggested to be a
      causal mechanism underlying the development of temporal lobe epilepsy. However,
      this hypothesis rests entirely on indirect correlational evidence. Here we
      demonstrate that cycloheximide, a protein synthesis inhibitor, blocked
      pilocarpine- and kainate-induced mossy fiber sprouting in rats, but did not
      prevent the subsequent development of spontaneous seizures or affect their
      frequency. These results provide direct evidence against a causal role for mossy
      fiber sprouting in temporal lobe epileptogenesis.

PMID- 9175593
TI  - Enhanced dimensional complexity of the EEG during memory for personal pain in
      chronic pain patients.
AB  - Associative connections between cortical cell assemblies representing pain
      related memories should be stronger and more extensive in subjects with chronic
      pain. To test this hypothesis, the dimensional complexity of the
      electroencephalograph (EEG) was examined during the actual experience as well as
      during memory for pain. Nine chronic pain patients and nine matched healthy
      controls participated in the study. During acute pain induction, acute pain
      recall, personal stress and pain recall, the EEG was recorded from 15 scalp
      sites. Non-linear analysis, based on the theory of deterministic chaos, revealed
      higher and more widespread EEG complexity in the patients compared to the healthy
      controls only during the recall of the personal pain scene. The personal stress
      scene was rated equally aversive but did not induce more EEG complexity. These
      more extensive and more readily accessible pain memories may be instrumental for
      the persistence of chronic pain.

PMID- 9175594
TI  - Intracutaneous injections of platelets cause acute pain and protracted
      hyperalgesia.
AB  - Suspensions of autologous, washed platelets were intracutaneously injected at the
      volar forearms of healthy volunteers. Injections of serum and vehicle served as
      control. Subjects and experimenter were blind with respect to the sequence of
      injections. In contrast to serum and solvent solution, platelets induced graded
      burning pain lasting several minutes. Platelet but not serum or vehicle
      injections dose-dependently caused large axon-reflex flares. At the site of
      platelet injections an induration developed and in parallel delayed mechanical
      and heat hyperalgesia was observed. Hyperalgesia to pressure and impact
      stimulation reached a maximum after 6 h and subsided during the following 48 h.
      Also, the threshold to heat stimuli decreased moderately by about 1 degree C, on
      average, after 24 h. Neither indurations nor hyperalgesia could be detected at
      the injection sites of serum or vehicle. The pathophysiological significance of
      this new inflammatory model for the research of posttraumatic hyperalgesia is
      discussed.

PMID- 9175595
TI  - Widespread neuronal expression of c-Fos throughout the brain and local expression
      in glia following a hippocampal injury.
AB  - Fos oncoprotein is an immediate early gene product and a marker of cell
      activation following a variety of insults. We have previously shown that a
      mechanical lesion to the hippocampus of adult mice induces a neuronal expression
      of the cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha
      (TNF alpha) whereas a lesion to the striatum does not. The role of these
      inflammatory cytokines in the pathophysiology of central neurons is still
      unclear. The present work was undertaken to study a possible correlation between
      the central expression patterns of c-Fos on the one hand and IL-1alpha and TNF
      alpha on the other hand. We show that Fos is expressed in a majority of brain
      neurons after a unilateral lesion to the hippocampus whereas it is confined to
      the site of injury when applied to the striatum, as previously described for the
      expression of the cytokines.

PMID- 9175596
TI  - Modulation of the arterial baroreceptor reflex by the vasopressin receptor in the
      area postrema of the hypertensive rats.
AB  - The role of arginine8-vasopressin (AVP) in regulation of the baroreceptor reflex
      in the area postrema was examined in anesthetized hypertensive rats. The
      sensitivity of the baroreceptor reflex in a one-kidney one clip (1K1C)
      hypertensive rats was increased in only the initial stage (2 weeks), in
      association with increase in blood pressure, and then returned to the normal
      level. This increase in the sensitivity of the baroreceptor reflex in the initial
      stage was reversed by microinjection of a V1 or V2 antagonist (1 microg) into the
      area postrema. AVP V2 receptor mRNA was expressed temporarily in the area
      postrema in this period. These results suggest that vasopressin receptors in the
      area postrema is important in regulating the sensitivity of the baroreceptor
      reflex.

PMID- 9175597
TI  - Migration of granule neurons in cerebellar organotypic cultures is impaired by
      methylmercury.
AB  - To examine whether abnormal migration of granule cells in the external granular
      layer during cerebellar development is in part of the etiology of fetal Minamata
      disease, organotypic culture of rat cerebellar slice was established. Migration
      of external granule cells pulse-labeled with bromodeoxyuridine (BrdU) toward the
      internal granular layer was inhibited by the presence of methylmercury (0-10
      microM) in a dose-dependent manner. Nuclear condensation and DNA fragmentation
      visualized by the indirect immunofluorescence method with anti-BrdU antibody and
      the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      method indicated that a large fraction of cells in the external granular layer
      underwent apoptotic death in the slices treated with 10 microM methylmercury.
      Thus, methylmercury inhibits the migration of cerebellar granule cells in a model
      system for neural development. The impaired migration was a possible cause of the
      apoptotic death of external granule cells.

PMID- 9175598
TI  - Nitric oxide synthase distribution in the goldfish Mauthner cell.
AB  - NADPH-diaphorase histochemical staining was used to assess the distribution of
      the enzyme nitric oxide synthase (NOS) in the goldfish brain, with the emphasis
      on the Mauthner (M-) cell, a reticulospinal neuron, and its inputs. Labeling was
      specific for certain cell types, including the M-cell, which stained heavily. The
      reaction product in this neuron was uniformly distributed along its axon, soma,
      and ventral and lateral dendrites. Afferents which synapse with the M-cell were
      also NADPH-diaphorase positive, including an identified class of inhibitory
      interneurons and the large myelinated club endings (LMCE) of eighth nerve fibers.
      The presence of NADPH-diaphorase in a lower level brainstem circuit that
      undergoes activity-dependent long-term potentiation of both excitatory and
      inhibitory synapses and is accessible for morpho-functional correlations provides
      the opportunity to elucidate the mechanism and role of nitric oxide at the single
      cell level.

PMID- 9175599
TI  - Motoneuronal location of the external urethral and anal sphincters: a single and
      double labeling study in the male and female golden hamster.
AB  - The location of external urethral (EUS) and anal sphincter (EAS) motoneurons was
      investigated in the golden hamster using the retrograde tracers horseradish
      peroxidase and cholera toxin B-subunit. Single and double labeling studies
      revealed that the motoneurons of the EUS and EAS were present in the same nucleus
      (nucleus of Onuf) ventrolaterally in the ventral horn of the caudal first sacral
      segment and throughout the second sacral segment. Within Onuf's nucleus the EAS
      motoneurons were located dorsomedial to the EUS motoneurons, which were located
      at the border of the gray and white matter. This location is similar to that in
      cat, dog, monkey and man, but differs from that in rat, Mongolian gerbil and
      domestic pig.

PMID- 9175600
TI  - Activation of chemosensitive neurons in the ventrolateral medulla by capsaicin in
      cats.
AB  - We examined effects of centrally administered capsaicin on sympathetic nerve
      activity (SNA), blood pressure (BP) and heart rate (HR) in chloralose
      anesthetized cats (n = 18). Upon perfusion of the lower brain stem via the left
      vertebral artery, capsaicin (0.1-1.0 microM) caused dose-dependent increases in
      preganglionic SNA (recorded from the white ramus T3) that were associated with
      rises in BP and HR. These responses resembled closely those obtained during
      perfusions with CO2-enriched (40-80%) saline. Coadministration of capsaicin and
      CO2 resulted in additively increased responses. The effects of capsaicin, but not
      those of CO2, were significantly counteracted by the capsaicin antagonist
      capsazepine and ruthenium red. These results suggest that a specific central
      chemosensitivity activated by vanilloid receptor agonists may modulate
      hypercapnic and/or acidic sympathoexcitatory stimuli in vivo.

PMID- 9175601
TI  - Effects of rat galanin and galanin message associated peptide (GMAP) on rat
      growth hormone secretion and stimulating effect of gamma-aminobutyric acid on
      galanin release from rat hypothalamus.
AB  - Immunoreactive galanin and galanin message associated peptide (GMAP) were
      detectable in rat hypothalamus in the concentration of 563 +/- 23 and 14.3 +/-
      3.1 fmol/hypothalamus, respectively. gamma-Aminobutyric acid (GABA) elicited a
      dose-related increase in galanin release from rat hypothalamic fragments, which
      was inhibited by picrotoxin, a GABA antagonist. Growth hormone (GH) secretion
      from rat anterior pituitary cells were stimulated by rat galanin, but not by
      GMAP. These findings suggest that hypothalamic galanin, but not GMAP, may play
      roles in GH secretion induced by GABAergic mechanisms in the rat.

PMID- 9175602
TI  - Conserved elements in the 5' regulatory region of the amyloid precursor protein
      gene in primates.
AB  - Oligonucleotides corresponding to conserved sites between the human and mouse
      amyloid precursor protein (APP) genes have been used to polymerase chain reaction
      (PCR) amplify and sequence the promoter region of the APP gene from chimpanzee,
      gorilla, orang-utan, papio and African green monkey. Several novel conserved
      potentially-regulatory sequences of the APP gene have been detected after
      alignment of the APP promoter sequences: an apolipoprotein E-B1 (APOE-B1) element
      at position -450, also present in the APOE gene, two activator protein-2 (AP-2)
      sites at positions -450 and -301 and an intermediate early-1 gene (IE1) site at
      position -280. These elements are conserved in all mammalian APP promoter
      sequences studied. Additionally a previously detected heat shock element (HSE) at
      position -317, and an activator protein-1 (AP-1) site at position -350 are also
      conserved. Knowledge of the essential regulatory elements at the APP gene
      constitute the basis for understanding its transcriptional control and subsequent
      model studies.

PMID- 9175604
TI  - Noradrenaline activates vasopressin neurons via alpha1-receptor-mediated Ca2+
      signaling pathway.
AB  - Noradrenaline (NA) (1-10 microM), dibutyryl-cAMP (1-5 mM), and forskolin (10-20
      microM) increased cytosolic Ca2+ concentration ([Ca2+]i) in isolated arginine
      vasopressin (AVP)-containing neurons in the hypothalamic supraoptic nucleus
      (SON). The NA-induced increase in [Ca2+]i in AVP-containing neurons was abolished
      by a specific alpha1-antagonist, prazosin (1 microM) and was markedly reduced
      when treated with a protein kinase A (PKA) blocker, H89 (40 microM). The NA
      induced [Ca2+]i was not altered by a protein kinase C (PKC) inhibitor, calphostin
      C (0.1 microM) and a PKC activator, TPA (100 nM). In general, NA, a known
      neurotransmitter in the SON, activates AVP-containing neurons via alpha1-receptor
      which is linked to stimulation of cAMP-PKA-regulated Ca2+ signaling pathway.

PMID- 9175603
TI  - NGF and BDNF increase the immunoreactivity of vesicular acetylcholine transporter
      in cultured neurons from the embryonic rat septum.
AB  - The expression of vesicular acetylcholine transporter (VAChT), which transports
      ACh into synaptic vesicles, is coregulated with choline acetyltransferase (ChAT).
      Therefore, the effects of nerve growth factor (NGF) and brain-derived
      neurotrophic factor (BDNF) on the levels of VAChT in cultured neurons from the
      septum of embryonic rats were investigated by immunocytochemistry. NGF and BDNF
      increased the number of VAChT-immunoreactive neurons by approximately 1.5-fold
      and enhanced the immunoreactivity in each positive cell. These results suggest
      that the neurotrophins enhance not only synthesis but also storage of ACh in
      septal neurons.

PMID- 9175605
TI  - Screening structural-functional relationships of neuropharmacologically active
      organic compounds at the nicotinic acetylcholine receptor.
AB  - The mechanisms of action and pharmacological effects on the nicotinic
      cholinoceptor of a large database of organic compounds were analyzed using a new
      computational procedure. This procedure is a screening method based on comparison
      of the molecular structures (shape and charge) of the putative active organic
      compounds. The resulting predictions can be used as an exploratory tool in the
      design of experiments aimed at testing the effects of several compounds on a
      target macromolecule. Unlike a conventional database search for structural
      similarities, the present method is able to circumscribe objectively the results
      to the most statistically significant molecules.

PMID- 9175606
TI  - Stereoselective increase in cholinergic transmission by R-(+)-hyoscyamine.
AB  - R-(+)-hyoscyamine, the dextro enantiomer of atropine, has been shown to amplify
      cholinergic transmission. R-(+)-hyoscyamine, unlike S-(-)-hyoscyamine, was able
      to increase acetylcholine release both in vitro and in vivo at a range of
      concentrations (10(-14) to 10(-12) M) and doses (5 microg/kg i.p.) which were
      inadequate for blocking muscarinic receptors. The increase over control values in
      ACh release was 15.9 +/- 2.1% in in vitro experiments performed in rat phrenic
      nerve-hemidiaphragm preparations (n = 6), and 63.3 + 16.3% in cortical
      microdialysis performed in free-moving rats (n = 5). The maximum ACh release was
      reached 60 min after R-(+)-hyoscyamine administration in in vivo experiments. At
      the same doses and concentrations, R-(+)-hyoscyamine was also able to elicit:
      antinociception of a cholinergic type (55.6-112.7% depending on the test used);
      complete prevention of scopolamine- and dicyclomine-induced amnesia; potentiation
      of muscular contractions electrically evoked in isolated guinea-pig ileum (16.7
      +/- 3.6%) and in rat phrenic nerve-hemidiaphragm (19.9 +/- 3.2%) preparations.
      Antinociception was performed using the hot-plate and acetic acid abdominal
      constriction tests in mice, and the paw pressure test in rats, while prevention
      of induced amnesia was evaluated in mice using the passive-avoidance test. The
      respective affinities (pA2) for R-(+)- and S-(-)-hyoscyamine vs M1 (rabbit vas
      deferens), M2 (rat atrium) and M3 (rat ileum) receptor subtypes were as follows:
      7.05 +/- 0.05/9.33 +/- 0.03 for M1; 7.25 +/- 0.04/8.95 +/- 0.01 for M2; 6.88 +/-
      0.05/9.04 +/- 0.03 for M3. The respective pKi values for R-(+)- and S-(-)
      hyoscyamine vs the five human muscarinic receptor subtypes expressed in Chinese
      hamster oocytes (CHO-K1) were as follows: 8.21 +/- 0.07/9.48 +/- 0.18 for m1;
      7.89 +/- 0.06/9.45 +/- 0.31 for m2; 8.06 +/- 0.18/9.30 +/- 0.19 for m3; 8.35 +/-
      0.11/9.55 +/- 0.13 for m4; 8.17 +/- 0.08/9.24 +/- 0.30 for m5.

PMID- 9175607
TI  - Characterization of phospholipase D activation by muscarinic receptors in human
      neuroblastoma SH-SY5Y cells.
AB  - The cholinergic regulation of phospholipase D activity was studied in SH-SY5Y
      human neuroblastoma cells with phosphatidylethanol formation as a specific marker
      for the enzyme activity. The muscarinic antagonists, hexahydrosiladifenidol and
      pirenzepine, inhibited carbachol-induced phosphatidylethanol formation in a
      concentration-dependent manner and the inhibitory constants indicated that
      muscarinic M1 receptors are responsible for the major part of the phospholipase D
      activation. The mechanism of receptor-mediated phospholipase D activation varies
      between different cell types and receptors. In SH-SY5Y cells, the carbachol
      induced phospholipase D activity was inhibited by protein kinase C inhibitors.
      Since both phospholipases D and C are activated by muscarinic stimulation in SH
      SY5Y cells, most of the phospholipase D activation is probably secondary to the
      protein kinase C activation that follows phospholipase C-mediated increase in
      diacylglycerols. Other kinases may be involved in the regulation since also a
      tyrosine kinase inhibitor decreased the phosphatidylethanol formation.
      Stimulation of G-protein(s) and increase in the intracellular Ca2+ concentration
      activated phospholipase D and may be additional mechanisms for the muscarinic
      regulation of phospholipase D in SH-SY5Y cells. Propranolol, an inhibitor of
      phosphatidic acid phosphohydrolase, increased the carbachol-induced formation of
      phosphatidic acid at the expense of 1,2-diacylglycerol. This indicates that
      phospholipase D contributes to the formation of 1,2-diacylglycerol after
      carbachol stimulation in SH-SY5Y cells.

PMID- 9175608
TI  - Ontogenetic and pharmacological studies on metabotropic glutamate receptors
      coupled to phospholipase D activation.
AB  - The present study was aimed at characterizing the metabotropic receptor subtype
      which is involved in the activation of phospholipase D (PLD) by glutamate in rat
      hippocampal slices. We first observed that the ontogenetic profile of glutamate
      induced hydrolysis of phosphoinositides and of phosphatidylcholine was strikingly
      similar. Both pathways were significantly activated by glutamate in tissue taken
      from 3-, 8- and 15-day old rats, but not in adult rats. PLD activation was
      strongest in slices taken from 8-day old rats. At this age, quisqualate had a
      higher potency for PLD activation (EC50: 0.6 microM) than 1S,3R-ACPD (EC50: 16
      microM) and DHPG, a specific activator of group I mGluR, was a full agonist at
      PLD activation (EC50: 3.5 microM) indicating an involvement of a group I mGluR
      (mGluR1 and 5). MCPG and AIDA, two putative antagonists at mGluR1 receptors,
      caused a small but (in the case of MCPG) significant inhibition. DCG-IV, an
      activator of group II mGluR, was a weak partial agonist at PLD activation (EC50:
      22 nM) while L-AP 4, an activator at group III mGluR, was totally inactive.
      Likewise, forskolin, a stimulant of cyclic AMP formation, was inactive either
      alone, or in combination with glutamatergic agonists. Pretreatment of the slices
      with pertussis toxin did not affect PLD activation. In summary, the glutamate
      mediated activation of hippocampal PLD, which occurs transiently during postnatal
      development, is mediated by a group I mGluR, possibly involving mGluR5.

PMID- 9175610
TI  - Bepridil-induced blockade of NMDA channels in rat hippocampal neurones.
AB  - Neurones isolated from the CA1 region of rat hippocampal slices by the
      "vibrodissociation" method were voltage-clamped in the whole-cell configuration.
      The currents through N-methyl-D-aspartate (NMDA) channels were recorded in
      response to the rapid application (solution exchange time <30 msec) of 100 microM
      aspartate (ASP) in a Mg2+-free solution in the presence of 3 microM glycine. When
      added to the ASP solution, bepridil (BPD) caused a concentration-dependent
      decrease in both peak and stationary currents due to an uncompetitive open
      channel blockade of NMDA channels. At -100 mV, the half-blocking concentration
      (IC50) for the stationary current was 14.01 +/- 0.17 microM (n = 10). The
      blocking and unblocking time constants were 7.4 +/- 0.3 x 10(3)/M/sec and 0.12 +/
      0.02/sec, respectively. Membrane hyperpolarization enhanced the BPD block. The
      equilibrium dissociation constant behaved as an exponential function of the
      membrane potential and increased e-fold every 37 mV.

PMID- 9175609
TI  - Antagonism of mGlu receptors and potentiation of EPSCs at rat spinal motoneurones
      in vitro.
AB  - The patch-clamp technique has been used to record synaptic responses, elicited by
      electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro
      spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha
      methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2
      amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4
      carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of
      mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression
      of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8)
      was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no
      significant effect on the depressant potency of AP4. Under control conditions,
      EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred
      of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05)
      to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358
      +/- 33 pC (n = 6) by MCPG. There was no significant difference between the
      enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact
      5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary
      afferent terminals presynaptic to motoneurones as well as in pathways via
      interneurones. These results are consistent with the presence of at least two
      types of presynaptic mGluR that modulate release of glutamate in segmental
      pathways convergent onto motoneurones. These receptors appear to be activated by
      interstitial glutamate tonically present in the present preparations.

PMID- 9175611
TI  - Progressive augmentation of striatal and accumbal preprotachykinin mRNA levels by
      chronic treatment with methamphetamine and effect of concurrent administration of
      the N-methyl-D-aspartate receptor antagonist MK-801.
AB  - We have assessed the time course of repeated administration of methamphetamine
      (METH; 4 mg/kg) and withdrawal on the levels of preprotachykinin (PPT) and
      preproenkephalin (PPE) mRNA abundance in the caudate-putamen (CPu) and nucleus
      accumbens (NAc) of the rat brain by in situ hybridization histochemistry.
      Neostriatal PPT mRNA levels rose gradually between days 1 and 6 of treatment,
      with the greatest elevation observed at day 6. After 6 days of daily injections
      twice per day, PPT mRNA increases in dorsomedial (172%) and ventromedial (196%)
      aspects of the CPu were significantly higher than in dorsolateral (147%) and
      ventrolateral (135%) subdivisions. Similarly, PPT mRNA levels were increased in
      the anterior CPu (163%) and NAc (121%). Concurrent administration of METH and the
      NMDA receptor antagonist MK-801 attenuated METH-induced increases of PPT mRNA in
      all aspects of the CPu at day 6 of treatment and completely prevented the
      increase in the NAc. Moreover, animals treated with METH for 6 days and then
      withdrawn for 15 days displayed PPT mRNA levels in striatum and accumbens that
      were statistically indistinguishable from those of controls. Adjacent sections
      from the same brains were used to assess PPE mRNA levels. PPE mRNA levels were
      transiently elevated in dorsal and ventral aspects of the CPu at day 1 and
      decayed to control levels at days 3 and 6. The results demonstrate that
      progressive treatment with methamphetamine causes stepwise elevation of
      preprotachykinin mRNA levels in the neostriatum. Moreover, the increase of
      neuropeptide mRNA shows selectivity, since PPE mRNA levels did not display
      progressive accumulation of message. The effects of progressive METH treatment on
      neostriatal PPT mRNA expression decay when the drug is withdrawn, suggesting that
      this neuropeptidergic system may not represent a neuroadaptation sustaining
      enduring sensitization to amphetamines, but may play a role in the progressive
      augmentation of locomotor activity elicited by this class of drug.

PMID- 9175612
TI  - Inhibition of AMPA receptor-stimulated 57Co2+ influx by D- and L-2-amino-4
      phosphonobutanoic acid (D- and L-AP4) and L-serine-O-phosphate (L-SOP) in
      cultured cerebellar granule cells.
AB  - This study describes the inhibition of 57Co2+ influx through Ca2+-permeable alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, consequent
      to the application of L-2-amino-4-phosphonobutanoic acid (L-AP4), D-AP4 and L
      serine-O-phosphate (L-SOP) in cultured cerebellar granule cells. The forskolin
      stimulated accumulation of cyclic AMP was inhibited by (2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine (L-CCG-1) with an IC50 = 491 +/- 135 nM and by L-AP4
      in a biphasic manner (IC50(1) = 232 +/- 61 nM and IC50(2) = >300 microM),
      confirming the presence of group II and group III mGlu receptors, respectively.
      57Co2+ influx was stimulated by kainate (EC50 = 42.2 +/- 11.3 microM) and, in the
      presence of 30 microM cyclothiazide, by (S)-5-fluorowillardiine (EC50 = 0.7 +/-
      0.1 microM) and (S)-AMPA (EC50 = 2.8 +/- 0.5 microM). The effects of the latter
      were abolished by 10 microM 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione
      (NBQX). L-AP4 (IC50 = >300 microM), D-AP4 (IC50 = >100 microM) and L-SOP (IC50 =
      199 +/- 6 microM) inhibited 6 microM (S)-AMPA-stimulated 57Co2+ influx, whereas L
      CCG-1 (up to 10 microM), 300 microM (RS)-3,5-dihydroxyphenylglycine, 300 microM
      (+/-)-baclofen and 1 mM carbachol were ineffective. Pre-incubation with either
      pertussis toxin (250 ng/ml, 48 hr), 1 mM dibutyryl cyclic AMP, or the potent
      group III mGlu receptor antagonist (RS)-alpha-cyclopropyl-4
      phosphonophenylglycine ((RS)-CPPG), tested at 400 microM, failed to alter the
      inhibition of AMPA receptor activity by 300 microM L-SOP. Unlike 10 microM NBQX,
      neither L-AP4, D-AP4 or L-SOP (tested at 1 mM) inhibited the binding of 10 nM (S)
      [3H]5-fluorowillardiine (a selective AMPA receptor ligand) to granule cell
      membranes. Therefore, in these neurones, high concentrations (>100 microM) of L
      AP4, L-SOP and D-AP4 inhibit Ca2+-permeable AMPA receptors by a mechanism
      distinct from known mGlu receptor action and at a site independent from that for
      AMPA receptor agonists.

PMID- 9175613
TI  - Sequence-independent effects of phosphorothiolated oligonucleotides on synaptic
      transmission and excitability in the hippocampus in vivo.
AB  - Antisense oligodeoxynucleotides (ODNs) have the potential to be a powerful tool
      for regulating gene expression and mRNA translation in spatially and temporally
      restricted domains. Prior to investigating the effects of antisense ODNs on
      hippocampal long-term potentiation, we investigated whether there are any non
      specific effects of ODNs on perforant path synaptic transmission in the dentate
      gyrus of both pentobarbital-anaesthetized and awake, freely moving rats. Single
      injections of phosphorothioated antisense ODNs (4 nmol) to the immediate early
      gene zif/268 caused a rapid (within minutes) and long-lasting (>24 hr) profound
      depression of the perforant path evoked field potentials. This depressive effect
      was due to the phosphorothioate modification since a depression was not seen with
      unmodified antisense ODNs, relative to saline controls. Furthermore, the effect
      was not sequence-specific since modified sense ODNs caused the same degree of
      depression. The depression caused by the modified antisense ODNs was dose
      dependent and specific to synaptic transmission, since antidromic population
      spikes elicited by mossy fibre stimulation were relatively unaffected compared to
      the orthodromic responses. A second unexpected side-effect of the modified ODNs
      was cellular hyperexcitability, such that bursts of epileptiform spikes in the
      EEG occurred both spontaneously and as a result of synaptic stimulation. While
      the mechanism of the synaptic depression remains unknown, these results indicate
      that phosphorothioate-modified ODNs exert profound non-specific effects on
      synaptic transmission in the hippocampus, that have the potential to seriously
      compromise any corresponding behavioural or electrophysiological studies.

PMID- 9175614
TI  - Adenosine A3 receptors potentiate hippocampal calcium current by a PKA
      dependent/PKC-independent pathway.
AB  - The modulation of high-threshold Ca current (I(Ca)) by adenosine receptors was
      studied using the voltage clamp method on acutely dissociated guinea pig
      hippocampal CA3 pyramidal neurons. When these neurons were exposed to adenosine
      in the presence of A1, A2a and A2b receptor antagonists, I(Ca) potentiation
      occurred at test potentials of -10 mV, but not at -40 mV. Similar potentiation
      also occurred using the A3 agonist N6-2-(4-aminophenyl)ethyl-adenosine (APNEA),
      either alone or in the presence of A1 and A2 antagonists. The putative A4 agonist
      2-phenylaminoadenosine (CV-1808; Cornfield et al., 1992) did not potentiate I(Ca)
      at four concentrations tested between 25 nM and 2500 nM. K0.5 for the APNEA
      induced potentiation was 25.4 nM, comparable to that determined in binding
      studies for the cloned receptor (15.5 nM; Zhou et al., 1992). I(Ca) potentiation
      by APNEA was blocked by intracellular application of WIPTIDE, a PKA inhibitor (p
      < 0.001), but was not affected by protein kinase C (PKC) inhibitor peptide (19
      36). These results indicate that: (1) A3 receptor activation can significantly
      potentiate I(Ca), and (2) because the A3 receptor has been linked to down
      regulation of adenylyl cyclase (Zhou et al., 1992), PKA appears to be negatively
      coupled to I(Ca).

PMID- 9175615
TI  - Effects of catechol-O-methyltransferase inhibition on the rates of uptake and
      reversibility of 6-fluoro-L-Dopa trapping in MPTP-induced parkinsonism in
      monkeys.
AB  - The uptake rate constant and the loss rate constant that expresses the
      reversibility of the uptake process of 6-[18F]fluoro-L-Dopa (FDOPA) were measured
      by positron emission tomography in the striatum of normal rhesus monkeys and in
      monkeys with unilateral lesions of the dopaminergic nigro-striatal pathway,
      induced by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP). Each animal was studied twice: with and without pretreatment of the
      catechol-O-methyltransferase (COMT) inhibitor Ro 40-7592, tolcapone. After
      pretreatment with tolcapone, there was a very significant increase in plasma
      FDOPA throughout the course of the study, accompanied by a significant decrease
      in its main metabolite, 3-O-methylfluorodopa. Tolcapone did not induce a
      significant change in the uptake rate constant in either the normal or the MPTP
      treated striatum. However, after tolcapone pretreatment, there was a significant
      decrease in the loss rate constant in the MPTP-treated striatum (25%) and a
      smaller, non-significant decrease in the normal striatum (13%). It is concluded
      that the COMT inhibitor tolcapone exhibits clear peripheral and central activity.
      As compared to peripheral COMT inhibitors, this central effect may help preserve
      and stabilize the synaptic levels of DA and, thus, further improve the effects of
      L-DOPA therapy in parkinsonian patients.

PMID- 9175616
TI  - Modulation of the discriminative stimulus properties of cocaine: comparison of
      the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists.
AB  - The present investigation examined the ability of serotonin (5-HT) agonists to
      substitute for, or alter (i.e. enhance or antagonize), the discriminative
      stimulus properties of a moderately low dose of cocaine (5 mg/kg) utilizing a two
      lever, water-reinforced FR 20 drug discrimination procedure in rats. In
      substitution tests, the 5-HT1A receptor partial agonists buspirone and gepirone,
      the 5-HT1A/B receptor agonist RU 24969 and the 5-HT1B/2C receptor agonist m
      trifluoromethyl-phenylpiperazine (TFMPP) failed to substitute for the cocaine
      stimulus, although RU 24969 did engender a maximum of 72% cocaine-lever
      responding. Fluoxetine (4 mg/kg) engendered primarily saline-appropriate
      responding. In combination tests, a fixed dose of either fluoxetine (4 mg/kg), RU
      24969 (0.5 mg/kg) or TFMPP (0.5 mg/kg) produced a leftward shift in the cocaine
      dose-response curve (0.313-5 mg/kg). In contrast, buspirone (2.5-20 mg/kg)
      resulted in a dose-dependent attenuation (approximately 60% reduction) of the
      cocaine stimulus. Moreover, a dose of 10 mg/kg of buspirone co-administered with
      various doses of cocaine (1.25-10 mg/kg) engendered a rightward shift in the
      cocaine dose-response curve. Gepirone in combination with cocaine neither
      enhanced nor antagonized the cocaine discriminative stimulus. Whereas 5-HT
      agonists do not fully substitute for cocaine, the present results demonstrate
      that 5-HT1B, but not 5-HT1A, receptor agonists can modulate the discriminative
      stimulus properties of cocaine in a manner similar to that observed following
      administration of the 5-HT reuptake inhibitor fluoxetine. The ability of
      buspirone, but not gepirone, to attenuate the cocaine stimulus probably reflects
      its dopamine (DA) D2 receptor antagonist properties and not its efficacy at 5
      HT1A receptors.

PMID- 9175617
TI  - Effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine on 5
      HTP-induced behaviour.
AB  - The effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine
      (5, 10, 20 mg/kg, i.p.) on wet dog shakes (WDS) and faecal pellet production
      induced by concurrently administered 5-hydroxytryptophan (5-HTP, 100 mg/kg, i.p.)
      given 30 min after carbidopa (25 mg/kg, i.p.) were investigated in rats. WDS
      scores peaked approximately 1 hr after giving 5-HTP and gradually declined over
      the next 2 hr. (-)-Tianeptine dose-dependently and significantly inhibited WDS.
      Inhibition became less marked with time after administration, but remained
      significant over the 3 hr period after the 10 and 20 mg/kg doses and during the
      first 40 min after the 5 mg/kg dose. (+)-Tianeptine caused slight inhibition
      without dose-dependence and slightly increased net inhibition when added to the (
      ) isomer (10 mg/kg). The induction of faecal pellet production by 5-HTP was
      significantly and dose-dependently inhibited by (-)-tianeptine. The (+) isomer
      neither altered this effect of 5-HTP nor its inhibition by (-)-tianeptine.
      Results show that inhibition of 5-HTP-induced WDS and faecal pellet formation by
      tianeptine was almost completely dependent on the (-) isomer.

PMID- 9175618
TI  - The effects of cholecystokinin A and B receptor antagonists on exploratory
      behaviour in the elevated zero-maze in rat.
AB  - The aim of the present study was to investigate the effects of cholecystokinin
      (CCK) CCK(A) and CCKB receptor antagonists SR 27897 B, devazepide, L 365260 and
      PD 135158 (CAM 1028) on exploratory behaviour in the elevated zero-maze in the
      rat. For further validation of the elevated zero-maze, the effects of a reference
      anxiolytic diazepam (0.25, 0.5, 1.0, 2.0 mg/kg), a non-benzodiazepine (BDZ)
      anxiolytic buspirone (0.04, 0.2, 1.0, 5.0 mg/kg), BDZ receptor inverse agonists
      FG 7142 (5, 10, 15, 20 mg/kg) and DMCM (0.1, 0.5, 1.0, 1.5 mg/kg), and a BDZ
      receptor antagonist flumazenil (10 mg/kg) were studied. Diazepam decreased the
      number of stretched-attend postures in all doses used and increased the
      percentage of time spent exploring in open parts at doses of 0.5 and 1.0 mg/kg.
      The effects of diazepam were blocked by flumazenil. FG 7142 and DMCM had effects
      only in subconvulsive doses (20 mg/kg and 1.5 mg/kg). Flumazenil and buspirone
      failed to show any effect. The CCK(A) receptor antagonists were also without any
      effect. The CCK(B) receptor antagonists L 365260 (1.0 and 5.0 mg/kg) and PD
      135158 (100 microg/kg) had a significant anxiolytic-like effect. The CCK(B)
      receptor antagonists increased the number of open part entries, the number of
      head dips, the percentage of time spent exploring in the open part and decreased
      the number of stretched-attend postures. These data support the hypothesis of the
      involvement of the CCK(B) receptor subtype in the neurobiological mechanisms of
      anxiety.

PMID- 9175619
TI  - NMDA receptor-dependent and -independent long-term depression in the CA1 region
      of the adult rat hippocampus in vitro.
AB  - We have investigated different stimulus parameters in an attempt to induce long
      term depression (LTD) in the CA1 region of adult rat hippocampus in vitro.
      Whereas 900 stimuli delivered at 1 Hz failed to induce LTD, 900 stimuli when
      delivered as 450 pairs (50 msec inter-stimulus interval) at 1 Hz induced
      significant and stable N-methyl-D-aspartate (NMDA) receptor-dependent LTD.
      However, 900 paired stimuli at 1 Hz induced LTD which was only partly blocked by
      the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoate (AP5).

PMID- 9175620
TI  - Pharmacological characterization of synaptic transmission through mGluRs in rat
      cerebellar slices.
AB  - The mGluR-mediated EPSP at parallel fibre-Purkinje cell synapses in the
      cerebellum was blocked concentration-dependently and reversibly by antagonists
      acting selectively on group-I mGluRs but not by an inhibitor of group-III
      receptors. The results provide pharmacological evidence that the receptor type
      responsible for the mGluR-EPSP is mGluR1.

PMID- 9175621
TI  - Identification of pore-forming subunit of P-type calcium channels: an antisense
      study on rat cerebellar Purkinje cells in culture.
AB  - Treatment of cerebellar neurones in culture with an antisense oligonucleotide
      (ODN) against alpha1A, reduced the whole-cell P-type calcium channel current
      relative to mismatch ODN treated controls (p < 0.001). Therefore, AgaIVA (50 nM)
      reduced whole-cell calcium current in mismatch and antisense treated cells by 70
      +/- 4 and 19 +/- 3%, respectively.

PMID- 9175622
TI  - Electroconvulsive shock increases the phosphorylation of cyclic AMP response
      element binding protein at Ser-133 in rat hippocampus but not in cerebellum.
AB  - ECS increased the Ser-133 phosphorylation of CREB in rat hippocampus, but not in
      the cerebellum, even though the basal level of phosphorylated CREB was higher in
      cerebellum. These results indicate that c-fos induction after ECS may be mediated
      by Ser-133 phosphorylation of CREB in rat hippocampus, but not in the cerebellum.

PMID- 9175623
TI  - Nuclear targeting of secretory proteins.

PMID- 9175624
TI  - Induction of Sp1 activity by prolactin and interleukin-2 in Nb2 T-cells:
      differential association of Sp1-DNA complexes with Stats.
AB  - The induction of the transcription factor Sp1 by prolactin (PRL) and interleukin
      2 (IL-2) was investigated in the PRL- and IL-2 responsive rat Nb2 T-cell line.
      Western analysis showed a rapid increase in Sp1 synthesis in Nb2 cells in
      response to PRL or IL-2. Elevation of Sp1 protein levels occurred within 15 min
      following PRL or IL-2 stimulation, reached a maximum by 1 h and was inhibited by
      cycloheximide, indicating de novo protein synthesis. Interestingly, dilution of
      confluent, growth-arrested Nb2 cells to low density also caused a rapid elevation
      in Sp1 suggesting that growth arrest may down-regulate Sp1 synthesis.
      Electrophoretic mobility shift assays using an Sp1 consensus oligonucleotide as
      probe showed a rapid but transient formation of a single PRL-inducible complex at
      30 min. In contrast, three IL-2-inducible complexes were formed at 30 min and
      persisted to at least 60 min. Mobility shift interference assays using specific
      Stat antibodies failed to detect Stat1alpha, Stat3 or Stat5 in the 30 min PRL
      inducible complex. In contrast, the IL-2 induced complexes contained Stat3 alone
      at 30 min and both Stat3 and Stat5 at 60 min. The PRL- and IL-2-inducible
      complexes did not contain the tumor suppressor protein, p53. The time dependent
      association of the Stat proteins with the IL-2-inducible complexes, but not with
      the PRL-inducible complex, suggests that the two mitogens may selectively utilize
      specific promoter elements for transcriptional activation of PRL- and IL-2
      responsive genes. Alternatively, the two mitogens may be activating different
      genes with Sp1-binding promoter elements for their mitogenic action in Nb2 cells.

PMID- 9175625
TI  - Trafficking of the androgen receptor in living cells with fused green fluorescent
      protein-androgen receptor.
AB  - The trafficking of the androgen receptor (AR) in transfected cells was studied
      using a green fluorescent protein (GFP)-AR chimera. The reporter molecule GFP
      enabled the localization of AR in living cells with a good spatial and temporal
      resolution. After the construction of GFP-AR and verification of the size of the
      fusion protein produced, we demonstrated that GFP-AR conserves the functional
      properties of the AR: GFP-AR had the same androgen-binding affinity as AR, and
      GFP-AR efficiently transactivated an androgen-responsive gene in response to
      synthetic androgen at 30 degrees C. The fusion protein was first detected
      throughout the cytoplasm without hormone, fluorescence becoming nuclear rapidly
      after androgen incubation. This hormone dependence of AR trafficking was
      confirmed by the use of the mutant GFP-AR-del4, which lacked the androgen-binding
      function. The mutant was localized in the cytoplasm in the absence of hormone,
      but the distribution was not modified by androgen incubation. An ACAS 570
      scanning laser cytometer was used to quantify fluorescence in a single living
      cell, first without and then with hormone. Different hormones and antihormones
      were tested to determine the dynamics of GFP-AR translocation into the nucleus.
      All the drugs used were able to induce nuclear translocation, and steady state
      level was rapidly attained within 1 h. The ratio of receptors in cytoplasmic and
      nuclear compartments was related to both affinity and concentration of ligand.
      The data from this follow-up study demonstrated for the first time the
      intracellular dynamics of the hormone-dependent trafficking of AR in a single
      living cell.

PMID- 9175626
TI  - Second messengers induced by the envelope protein of a retrovirus.
AB  - The envelope protein (gp52) of the mouse mammary tumor virus (MMTV) can stimulate
      RNA synthesis via binding to its cellular receptor on mammary epithelium. This
      effect was mimicked by either nitric oxide (NO) or 8-bromo-cGMP and was blocked
      by an NO inhibitor. Furthermore, the effects of gp52 and 8-bromo-cGMP were not
      additive at maximal concentrations, suggesting that they were using the same
      signaling route. Finally, gp52 elevated cGMP levels in mammary epithelium. These
      data suggest that gp52 activates the following transduction pathway in this
      tissue: gp52-->NO synthase-->NO-->soluble guanylate cyclase cGMP RNA synthesis.
      In contrast to the mammary gland, gp52 inhibited RNA synthesis in the diaphragm.
      However, the effect was again mimicked by NO, blocked by an NO inhibitor, and the
      effects of gp52 and NO were not additive. Therefore, it appears that gp52 is
      using the NO-cGMP pathway in both tissues, but that muscle tissue may be more
      susceptible to the toxic effects of NO.

PMID- 9175627
TI  - Characterization of an androgen response element within the promoter of the
      epididymis-specific murine glutathione peroxidase 5 gene.
AB  - We have shown in earlier studies, using a mouse model, that the expression of the
      glutathione peroxidase 5 protein (GPX5) is restricted to the epididymis and that
      the accumulation of its corresponding mRNA is hormonally, spatially and
      temporally regulated throughout postnatal development. We report here, using run
      on assays, transient expression experiments as well as gel-shift and footprinting
      analyses on the findings that at least part of the androgenic control of the GPX5
      expression is exerted at the transcriptional level via an androgen response
      element localized in the distal promoter region of the GPX5 gene. The gpx5
      androgen response element (ARE) is found to be consistent with the consensus
      palindromic steroid-receptor target sequence 5'-AGWACWnnnTGTYCT-3' but exhibits a
      quite weak conservation in the left half site. The data presented here further
      expand the diversity of sequence able to confer androgen responsiveness.

PMID- 9175628
TI  - Transcriptional activation of the human growth hormone gene by ras oncogene.
AB  - ras Oncogenes play an important role in causing cellular transformation and
      proliferation. They have been implicated in the formation of many human tumors
      but only rarely been identified in pituitary adenomas. We studied the effect of
      ras activation on growth hormone (GH) production. Transcriptional regulation of
      human GH was investigated by transient transfections in a pituitary cell line GH4
      using different promoter fragments cloned 5' of the luciferase reporter gene (
      344 to -83). Co-transfection of the constitutively active valine 12 mutant ras
      oncogene (V-12 ras) resulted in a selective and dose-dependent stimulation of 
      344-GH/Luc activity. This effect is pituitary-cell specific as activation of the
      human GH promoter by ras was absent in a human chorion carcinoma cell line JEG3.
      Co-transfection of protein kinase inhibitor did not influence ras mediated
      stimulation of the human GH promoter. Investigations of several deletion
      constructs of the human GH promoter revealed that elements between - 145 and - 83
      are sufficient to transduce ras signaling. This region contains two Pit-1
      bindings sites as well as a Zn-15 binding site. These studies demonstrate
      transduction of ras signaling to the human GH promoter through a protein kinase A
      (PKA) independent signaling pathway. This separate transduction mechanism may
      convey regulation by yet unknown factors.

PMID- 9175629
TI  - Retinoid X and retinoic acid receptors interact with transcription factor II-B by
      distinct mechanisms.
AB  - Nuclear hormone receptors are believed to modulate target gene expression by
      interacting with the general transcriptional machinery of the cell. We
      demonstrate here that two otherwise closely related members of the nuclear
      hormone receptor family, retinoid acid receptors (RARs) and retinoid X receptors
      (RXRs), exhibit significant differences in their interactions with the
      transcriptional machinery. RARs display a strong constitutive interaction with
      transcription factor II-B (TFIIB) that requires the TFIIB C-terminus, whereas RXR
      exhibits a weaker, hormone-stimulated interaction with the TFIIB that maps
      outside of the TFIIB C-terminus. Use of a dominant-negative mutant of TFIIB
      suggests that the TFIIB interaction is essential for full transcriptional
      activation by RXR.

PMID- 9175630
TI  - o,p'-DDT and its metabolites inhibit progesterone-dependent responses in yeast
      and human cells.
AB  - Using a combination of in vitro assays we have evaluated whether DDT metabolites
      can interact with the progesterone receptor pathway in yeast expressing human
      progesterone receptor (hPR) and in T47D human breast cancer cells which express
      endogenous hPR. In transactivation assays using both yeast and T47D cells, o,p'
      DDT and the metabolites p,p'-DDT, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, p,p'
      DDA, and DDOH inhibited progesterone-induced reporter gene activity in a dose
      dependent manner. None of the DDT metabolites functioned as hPR agonists. Whole
      cell competition binding assays using T47D cells indicated that the inhibitory
      effects of DDT metabolites on progesterone-dependent activites may occur through
      both hPR-dependent and hPR-independent pathways. Our results and previous reports
      of DDT metabolites interacting with estrogen and androgen receptors suggests that
      this class of environmental chemicals may interact with numerous hormone receptor
      signaling pathways.

PMID- 9175631
TI  - Down-regulation of the mdr gene by thyroid hormone during Xenopus laevis
      development.
AB  - The developmental regulation of mdr in Xenopus laevis has been investigated. Xe
      mdr expression was first detected in the early tadpole stage just prior to the
      onset of feeding and increased during intestinal development, with a sharp
      decline at metamorphosis. Xe-mdr expression was found to be localized
      specifically to the epithelial cells lining the intestinal tract. When
      premetamorphic tadpoles were treated with 5 nM triiodothyronine to induce
      metamorphosis, a significant decrease in mdr message and protein was observed
      after 3 days, a time at which the primary epithelium remained intact.
      Furthermore, in thyroid-hormone treated primary cultures of brush border
      epithelial cells, a reduction in mdr message also was observed. These results
      demonstrate that the Xe-mdr gene is developmentally regulated and suggest a role
      for thyroid hormone in this process. This is the first report of a naturally
      occurring substance that can down-regulate mdr gene expression in vivo.

PMID- 9175632
TI  - Stable expression of normal and mutant human ACTH receptor: study of ACTH binding
      and coupling to adenylate cyclase.
AB  - Point mutations of the human ACTH receptor have been reported in some patients
      with a familial glucocorticoid deficiency syndrome. To demonstrate that these
      mutations were responsible for the disease, it was necessary to develop a model
      in which characteristics of normal and mutant receptors could be studied. We have
      developed a stable expression model in order to characterize the human ACTH
      receptor by binding studies and functional coupling to adenylate cyclase. After
      confirmation of the stable integration of receptor constructs, ACTH dose
      responses for the production of cAMP were carried out. The EC50 for ACTH were 2.9
      +/- 0.2 x 10(-10) M and 2.4 +/- 0.8 x 10(-10) M, respectively, for two different
      clones stably expressing the normal human ACTH receptor. EC50 calculated for
      clones expressing either one of the two studied mutant receptors (C251F and
      D107N) were increased: 4.1 +/- 0.9 x 10(-9) M and 6.4 +/- 1.3 x 10(-9) M
      respectively. These values were similar to that obtained with M3 parental cells
      (4.7 +/- 0.8 x 10(-9) M). Binding studies were performed on the same clones.
      Scatchard analysis showed that clones expressing the normal receptor possessed
      high affinity binding sites for ACTH, with K(d) = 5.8 +/- 2.4 x 10(-10) M and 6.9
      +/- 3.6 x 10(-10) M, respectively, for the two different studied clones. A second
      type of sites, with low affinity (K(d) around 10(-8) M), was also present. There
      was no ACTH binding to the high affinity binding sites for the two clones
      expressing either one of the mutant receptors. An impaired binding of ACTH to its
      receptors is then responsible for the absence of biological response to ACTH in
      patients carrying these mutant ACTH receptors.

PMID- 9175633
TI  - Parathyroid hormone-related protein and human myometrial cells: action and
      regulation.
AB  - Parathyroid hormone-related protein (PTH-rP), like parathyroid hormone (PTH),
      acts on myometrial smooth muscle to cause relaxation, and PTH-rP expression has
      been demonstrated in the myometrium of pregnant and estrogen-treated nonpregnant
      rats and in human myometrium, leiomyomata and separated myometrial smooth muscle
      cells in culture. PTH-rP may facilitate the myometrial quiescence characteristic
      of the first 95% of normal pregnancy and uterine vasorelaxation. This study was
      conducted to explore further the function and regulation of expression of PTH-rP
      in human myometrium. Treatment of myometrial smooth muscle cells with analogs of
      PTH-rP caused an increase the intracellular levels of cAMP and treatment of
      myometrial cells with forskolin or dibutyryl cyclic AMP caused an increase in the
      levels of PTH-rP mRNAs. Tetradecanoyl phorbol acetate (TPA) and okadaic acid
      caused a striking increase in the levels of PTH-rP mRNAs, much greater than that
      evoked by forskolin, dibutyryl cAMP, or transforming growth factor-beta (TGF
      beta). These findings are supportive of the conclusion that myometrial cells
      respond to PTH-rP with activation of adenylyl cyclase and that PTH-rP gene
      expression may be modulated by way of a number of distinct intracellular
      signaling pathways.

PMID- 9175634
TI  - Characterization of the 5'-flanking region of the gene for the cAMP-inducible
      protein kinase A subunit, RIIbeta, in Sertoli cells.
AB  - Activation of cyclic AMP-dependent protein kinases (protein kinase A, PKA) by
      gonadotropins and cyclic AMP (cAMP) plays an important role in the regulation of
      testicular functions. A regulatory subunit, RIIbeta, of PKA is transcriptionally
      induced in rat Sertoli cells in response to treatment with cAMP. The present
      study addresses regulatory mechanisms leading to increased transcription of the
      rat RIIbeta gene. We have localized a footprint which overlaps one of the major
      transcription initiation sites in the basal promoter (-293 to -123). One of the
      proteins binding this sequence belongs to the NF-1 family of transcription
      factors. We also observed binding to a basic helix-loop-helix (bHLH) response
      element. Furthermore, transfection studies of various 5'-deletions of the rat
      RIIbeta gene in primary cultures of rat Sertoli cells and in peritubular cells
      revealed the presence of an upstream region (-723 to -395, cAMP-responsive
      region) inhibiting basal expression from the rat RIIbeta gene only in Sertoli
      cells. This region was found to enhance cAMP responsiveness in Sertoli cells but
      not in peritubular cells. Interactions with downstream elements seemed to be
      important for the function of the cAMP-responsive region. Although some short
      stretches reveal homology to the cAMP-responsive regions of other slowly cAMP
      responding genes, and an AP-1-like element is present, no strong resemblance to
      any known regulatory element responsive to cAMP is found.

PMID- 9175635
TI  - Enhanced restriction site mutation (RSM) analysis of 1,2-dimethylhydrazine
      induced mutations, using endogenous p53 intron sequences.
AB  - The restriction site mutation (RSM) assay was used to study the mutational
      sensitivities of three target regions of the murine p53 gene. The non-coding
      intron 6 target region was compared with the coding regions exon 4 and exon 5
      with respect to their relative sensitivity to the induction of mutations by 1,2
      dimethylhydrazine (DMH). Our results demonstrated that the majority of induced
      mutations detected were in the intron 6 gene region. A total of 15 enzyme
      resistant restriction sites were detected in DMH treated mice, nine of these in
      the intron 6 region, four in the exon 4 region and two in the exon 5 region. The
      elevated sensitivity of the intron 6 region was exemplified by our detection of
      spontaneous mutations in this region; two resistant restriction sites were
      detected in untreated animals. No spontaneous mutations were detected in either
      of the exon sequences studied here, nor have any been detected in exon targets in
      our previous in vivo RSM analyses. The mutations induced by DMH were mostly GC-
      >AT transitions, as were the spontaneous mutations identified. The mutation
      frequencies calculated by the inclusion of a mutant internal standard (MIS) in
      the RSM method, revealed that the non-coding intron 6 region and the exon 4
      region had a 10-fold higher mutation frequency than the exon 5 region. This
      heterogenous distribution of mutations and their differential mutation
      frequencies, were probably a consequence of the greater selection in the coding
      regions in p53 function. However, the actual mechanism of differential mutation
      induction is, as yet, to be defined.

PMID- 9175636
TI  - Induction and persistence of cytogenetic damage in mouse splenocytes following
      whole-body X-irradiation analysed by fluorescence in situ hybridization. III.
      Chromosome malsegregation/aneuploidy.
AB  - Transgenic mice with foreign DNA inserted into three pairs of chromosomes were
      exposed to 2 Gy X-rays in order to study the induction and persistence of
      chromosome malsegregation and aneuploidy up to 28 days after exposure. By tracing
      the marker chromosomes in cytokinesis-blocked binucleated splenocytes using
      fluorescence in situ hybridization (FISH), reciprocal products of chromosome
      malsegregation in the daughter nuclei were analysed. FISH with murine minor
      satellite DNA was employed to detect chromosome loss (MN with a centromere) in
      binucleated splenocytes. In addition to its clastogenic effects, X-irradiation
      also showed aneugenic activity, which was observed as centromere positive
      micronuclei (C + MN) and malsegregated marker chromosomes detected by FISH. The
      initial frequency of micronuclei (MN) analysed by Acridine Orange staining
      immediately after X-ray exposure was found to be 42.3 per 100 binucleated cells.
      The MN frequency declined in an exponential manner and at day 14, reached about
      half the value observed immediately after irradiation and 14% MN were detected at
      day 28. Of these MN, 25% were centromere positive at day 0 as detected by minor
      satellite signal after FISH. The percentage C + MN increased further at day 3 and
      declined at day 14 to the level observed at day 0. There were 7.6% malsegregated
      cells immediately after X-irradiation as analysed by two colour FISH. This value
      increased further during later intervals and remained stable until day 28. A
      combination of the Acridine Orange staining and FISH with minor satellite DNA and
      marker DNA to detect aneuploidy and chromosome malsegregation, was utilized in
      the present study to demonstrate the induction and persistence of aneugenic and
      clastogenic damage in transgenic mice irradiated in vivo.

PMID- 9175638
TI  - Studies on the photobiological activity of two naturally occurring furochromones,
      visnagin and khellin, in Chlamydomonas reinhardtii.
AB  - Irradiation of arg-1 cells of the green alga Chlamydomonas reinhardtii with UV-A
      in the presence of visnagin (10 microg/ml) produced weak mutagenic effects when a
      fluence rate of 5.1 W/m2 and fluences of 1.5-36.7 kJ/m2 were applied. A maximum
      number of revertants was obtained at approximately 9.2 kJ/m2. When a fluence rate
      of 20.4 W/m2 was used the photomutagenicity of visnagin was markedly enhanced
      with fluences of > or = 36.7 kJ/m2. In survival experiments with a fluence rate
      of 5.1 W/m2 the surviving fraction decreased continuously to approximately 4%. In
      experiments with a fluence rate of 20.4 W/m2, however, higher survival rates were
      observed compared at equal UV-A doses. Visnagin was much less phototoxic and
      photomutagenic than bergapten when compared at equimolar concentrations and equal
      UV-A doses. Re-irradiation with UV-A in the absence of unbound visnagin did not
      alter survival and mutagenicity which had been induced by the first treatment.
      The mutation frequency plotted versus the UV-A fluence exhibited second-order
      kinetics. Khellin showed only marginal photosensitizing capacity and no
      significant mutagenicity up to a concentration of 100 microg/ml and a total UV-A
      fluence of 73.4 kJ/m2.

PMID- 9175637
TI  - Indication for thresholds of chromosome non-disjunction versus chromosome lagging
      induced by spindle inhibitors in vitro in human lymphocytes.
AB  - Risk assessment from exposure to spindle inhibitors should take into account the
      possibility of threshold concentration-response curves for aneuploidy induction.
      We analysed concentration-dependent induction of chromosome non-disjunction by
      well known spindle poisons (colchicine, carbendazim, mebendazole and nocodazole)
      and a reference clastogen, methyl methanesulphonate (MMS) in vitro in human
      lymphocytes; and integrated these findings with earlier results of chromosome
      loss in micronuclei. Chromosome non-disjunction was estimated on cytokinesis
      blocked lymphocytes after simultaneous fluorescent in situ hybridization
      labelling with two chromosome-specific centromeric probes (chromosomes 1 and 17).
      The frequencies of spontaneous non-disjunction showed important inter-individual
      variations and were surprisingly high (7.04-15.39%). Lower concentrations of
      aneugens did not induce a statistically significant increase of non-disjunction
      frequencies over the respective control levels, whereas higher concentrations
      clearly induced a concentration-dependent increase in the non-disjunction
      frequencies with the four aneugens tested. On the contrary, even at high
      concentrations, MMS induced a slight increase in the frequency of non-disjunction
      but without being statistically significant when compared with the control
      frequencies. We estimated the inflection points, the first statistically
      significant concentrations, the last non-statistically significant concentrations
      and the number of events from concentration-response curves of chromosome non
      disjunction and chromosome loss. A threshold-type of concentration-response for
      non-disjunction is highly probable for colchicine and nocodazole. For carbendazim
      and mebendazole the inflection point fell above the first statistically
      significant concentrations. But since it is obvious from dose-response curves
      where the inflection point/threshold lies, it appears that the model might be
      picking up some irregularities (possibly due to experimental variability in the
      dose-response curve at concentrations greater than the threshold). For accurate
      estimation of the threshold, analysis of more concentrations or more cells might
      be needed. Our data strongly indicate that in cultured human lymphocytes
      chromosome non-disjunction is a major mechanism of aneuploidy induction by
      spindle inhibitors and since non-disjunction occurs at lower concentration than
      chromosome loss, the aneuploidy threshold should be estimated on the basis of non
      disjunction rather than on micronuclei frequencies (chromosome loss).

PMID- 9175639
TI  - Genomic instability in haematopoietic cells of F1 generation mice of irradiated
      male parents.
AB  - Preconceptional paternal irradiation has been implicated as a causal factor in
      childhood cancer and it has been suggested that this exposure to radiation may
      play a role in the occurrence of childhood leukaemia clusters in the vicinity of
      nuclear installations. Using a transgenic mouse system employing a lambda shuttle
      vector allowing mutations (in the lacI gene) to be analysed in vitro, we have
      investigated the possibility that preconceptional paternal irradiation can lead
      to such transgenerational transmission of genomic instability. We have examined
      the mutation frequencies in vector recovered from the bone-marrow cells of the F1
      offspring of male parents exposed to doses of gamma-rays of 0.1-4 Gy. Our results
      show that as parental dose increases there is a trend towards higher mutation
      frequency in vector recovered from the DNA of bone-marrow of F1 progeny. At 4 Gy
      the frequency of mutations was increased by a factor of approximately two
      (control mutation frequency, 2.39 x 10(-5); mutation frequency in offspring of 4
      Gy male group, 4.26 x 10(-5); P < 0.001). We were unable to confirm reports of
      spermatogenesis stage sensitivity. The 2-fold increase in mutation frequency was
      evident in offspring derived from stored spermatozoa (irradiated transgenic males
      mated with unirradiated non-transgenic females 1-7 days after irradiation). Our
      data indicates that there exists a route for transgenerational transmission of
      factor(s) leading to genomic instability in F1 progeny, resulting from
      preconceptional paternal irradiation.

PMID- 9175640
TI  - The detection of genotoxin-induced DNA adducts in the common mussel Mytilus
      edulis.
AB  - In order to establish the capacity of Mytilus spp. to form genotoxin-DNA adducts,
      a series of in vitro and in vivo studies were conducted in which tissue samples
      and animals were exposed to five model genotoxins. Following the in vitro
      characterization of the major adducts induced by the compounds, a series of in
      vivo studies were conducted to determine if the levels of genotoxin-DNA adduct
      formation followed a dose response. The results of these studies suggested that
      under appropriate conditions, DNA adducts in the hepatopancreas could be used as
      molecular dosimeters of exposure to genotoxic compounds in the species. However,
      these studies also revealed that the successful detection of such genotoxin-DNA
      adducts depends largely upon their chromatographic properties and thus the vigour
      of the characterization undertaken.

PMID- 9175641
TI  - Characterization of the CYP isozyme profile induced by cyclohexanol.
AB  - In a previous report we described the ability of cyclohexanol to induce CYP
      activity. In order to characterize this induction we tested the capacity of liver
      S9 from rats orally treated with cyclohexanol for 5 days, to activate several
      carcinogenic nitrosamines into mutagens in the Salmonella typhimurium TA100 test
      system. Additionally, Western blot analysis of hepatic microsomes from the same
      treated animals were analysed with specific antibodies against P450 protein
      families 1A1/A2, 2B1/B2 and 2E1. Cyclohexanol-S9 mixture was more efficient in
      activating the following nitrosamines: N-nitrosodimethylamine (NDMA), N
      nitrosodipropylamine (NDPA), N-nitrosomethylpropylamine (NMPA), N
      nitrosodibutylamine (NDBA), and N-nitrosopyrrolidine (NPYR) into bacterial
      mutagens than S9 from non-treated animals. The mutagenicity of N
      nitrosodiethylamine (NDEA) was not modified in the presence of S9 from
      cyclohexanol-treated animals. Since the main metabolic pathway leading to the
      production of mutagenic intermediates of NDMA and NPYR is catalysed by isozyme
      CYP2E1 and that of NDPA, NMPA and NDBA by CYP2B1/B2, mutagenicity experiments
      predicted that cyclohexanol induces these two P450 isozyme families. Western blot
      analysis confirmed the results of the mutagenicity assay, showing an increase in
      the intensity of CYP2E1 and CYP2B1/B2 protein bands in hepatic microsomes from
      cyclohexanol treated rats in comparison with non-treated controls. Bacterial
      mutagenicity tests with specific pro-mutagens were good predictors of the P450
      induction properties of cyclohexanol.

PMID- 9175642
TI  - Industrial Genotoxicology Group collaborative trial to investigate cell cycle
      parameters in human lymphocyte cytogenetics studies.
AB  - Human lymphocyte cultures have been used for many years for assessing the in
      vitro clastogenic potential of test substances. In these assays the harvest time
      should be based on the cell cycle time in order to ensure that cells are sampled
      at an appropriate time for the detection of clastogenic effects. The sources of
      variation in the cell cycle time in routine cytogenetic assays have not been well
      studied. Consequently 13 laboratories, all members of the Industrial
      Genotoxicology Group, participated in a collaborative study to measure the
      variation in cell cycle time in cultured human peripheral blood lymphocytes under
      various conditions. The study was performed in two phases, spaced 6 months apart.
      The average generation time (AGT) was measured by the incorporation of
      bromodeoxyuridine. Very similar AGTs were found in the presence and absence of S9
      mix. The mean AGT (mean of four donors) in each laboratory varied from 11.2 to
      17.1 h, indicating there is significant variability in cell cycle times of human
      peripheral blood lymphocytes between laboratories. There was greater variation
      between laboratories than within laboratories. A comparison of AGT values at 72 h
      performed in experiments at least 6 months apart indicated good reproducibility
      in most laboratories. The study indicates that a 24 h post-treatment harvest may
      result in the analysis of very few first division cells unless very significant
      cell cycle delay is induced by the test substance. It was also found that a post
      harvest time equivalent to 1.5 cell cycles will result in an approximately equal
      mixture of first and second division cells and therefore should by suitable for
      assessing both the induction of chromosome aberrations and polyploidy.

PMID- 9175643
TI  - Assessment of the potential in vivo genotoxicity of three trihalomethanes:
      chlorodibromomethane, bromodichloromethane and bromoform.
AB  - Chlorination of drinking water results in the formation of chlorodibromomethane,
      bromodichloromethane and bromoform. These trihalomethanes have all shown evidence
      of genotoxicity in bacterial and mammalian cell systems in vitro and some
      evidence of carcinogenicity in rodents. Chlorodibromomethane and
      bromodichloromethane have previously been tested in the mouse micronucleus test
      and did not induce chromosome damage, but results from two previous micronucleus
      tests on bromoform are somewhat contradictory. In the present study, bromoform
      was tested in the mouse bone marrow micronucleus test in order to reassess the
      response in this system; all three compounds were evaluated using the rat liver
      unscheduled DNA synthesis test. Trihalomethanes are well absorbed by the oral
      route which was selected for this study as being that most relevant to humans.
      Bromoform did not induce micronuclei in mouse bone marrow, and
      chlorodibromomethane, bromodichloromethane and bromoform did not cause
      unscheduled DNA synthesis in rat liver. These trihalomethanes have not shown any
      evidence of genotoxicity in vivo and are most unlikely to have any significant
      genotoxic activity in mammals. Their mode of action as rodent carcinogens remains
      unexplained.

PMID- 9175644
TI  - A method for detecting sister chromatid exchanges using prematurely condensed
      chromosomes and immunogold-silver staining.
AB  - We have developed a method for detecting sister chromatid exchanges using
      premature chromosome condensation and immunogold labelling followed by silver
      enhancement. Cells were grown in bromodeoxyuridine before sister chromatid
      exchanges were generated with mitomycin C. Calyculin A was then used to condense
      the chromosomes prematurely. Finally, incorporated bromodeoxyuridine was detected
      using a gold-conjugated antibody followed by silver enhancement. Exchanged
      chromatids could easily be seen in the resulting chromosomes. This simple method
      allows sister chromatid exchanges to be detected with great sensitivity and
      resolution.

PMID- 9175645
TI  - Sodium phenobarbital-enhanced mutation frequency in the liver DNA of lacZ
      transgenic mice treated with diethylnitrosamine.
AB  - To investigate how a carcinogenic promoter acts on cells mutated by an initiator,
      we used as a model, lacZ transgenic mouse and a positive selection system.
      Preliminary data for the mutational events in liver DNA of the mice was generated
      using diethylnitrosamine (DEN) and sodium phenobarbital (S-PB) as initiator and
      promoter, respectively. In our first experiment, male MutaMice received a single
      i.p. injection of saline or 100 mg/kg DEN and were fed a normal diet for 7 days
      and 500 p.p.m. S-PB in the diet for 21 days. Liver DNA was harvested after a 1
      night fast on days 7 and 28 post-DEN treatment. In our second experiment, male
      mice received a single i.p. injection of phosphate buffered saline or 50 mg/kg
      DEN and were fed a normal diet for 7 days, a diet with S-PB for 14 days and then
      a normal diet for 7 days. Liver DNA was harvested after a 1 night fast on days 7,
      21 and 28 post-DEN treatment. The S-PB diet enhanced absolute and relative liver
      weights in all groups. The single intraperitoneal dose of 50 or 100 mg/kg DEN
      induced high mutation frequencies (MF) in liver, lacZ genes on days 7, 21 and 28.
      There were no remarkable differences of the MF among any sampling days for
      animals receiving DEN and a normal diet. S-PB feeding at 500 p.p.m. for 21 days
      failed to affect the MF in groups given saline or 100 mg/kg DEN. On the other
      hand, when 50 mg/kg DEN was given, S-PB feeding at 500 p.p.m. for 14 days
      elevated the MF in liver DNA on days 21 and 28 to approximately 1.8 and 4.0 times
      the MF, respectively, of the mice fed the normal diet. Consequently, S-PB might
      preferentially promote certain initiated cells participating in a balance between
      cell death and proliferation.

PMID- 9175646
TI  - Large deletions partially external to the human hprt gene result in chimeric
      transcripts.
AB  - We postulated that gene fusions sometimes occur in normal cells as a result of
      gene rearrangements as have been observed involving oncogene loci in tumours. To
      test this, we searched for fusion-gene transcripts in selected human T-lymphocyte
      large deletion mutations of the hypoxanthine-guanine phosphoribosyltransferase
      (hprt) gene using the 3' rapid amplification of cDNA ends (RACE) technique.
      Aberrant hprt-containing transcripts were observed in seven out of 19 mutants
      (approximately 36%) indicating that a surprising number of these rearrangements
      code for processed mRNAs. RNA splicing and polyadenylation occurred downstream of
      the non-deleted hprt sequence in chimeric transcripts and the majority resulted
      from mutants with fusions of hprt into regions containing a repetitive element
      (Alu, LINE or microsatellite).

PMID- 9175647
TI  - Suppression of UV-induced mutations by wild-type p53 protein in human
      osteosarcoma cells.
AB  - We have examined whether the tumour suppressor p53 protein suppressed UV-induced
      mutations in the hypoxathine-guanine phosphoribosyl transferase (HPRT) gene and
      in the supF gene of the shuttle vector plasmid pMY189. We used human osteosarcoma
      Saos-LP12 cells, in which wild type (wt) p53 protein was induced by treatment
      with isopopyl-beta-D-thiogalactopyranoside. The induction of wt p53 protein
      suppressed UV-induced mutations but not spontaneous mutations in the HPRT gene.
      The frequency of UV-induced mutations induced by UV-irradiation of the plasmid
      was also significantly lower in cells with induced wt p53 protein than in the
      uninduced cells. In addition, we found that frequency of G : C to A : T
      transition mutations which occurred at the 3' base pair of dipyrimidine sites
      were significantly lower in the cells with induced wt p53 protein than in the
      uninduced cells. These findings suggest that wt p53 protein may play roles in
      modulating DNA repair pathway, resulting in the suppression of UV-induced
      mutations.

PMID- 9175648
TI  - Complementary AIDS therapies: the good, the bad and the ugly.
AB  - HIV-infected/AIDS patients seem to frequently use complementary therapies, yet
      definitive information in this area is difficult to obtain. The aim of this
      systematic review is therefore to assess the published data on the use of
      complementary medicine by HIV-infected/AIDS patients. A computerized systematic
      literature search was carried out. Data on prevalence of complementary medicine
      (CM) use, effectiveness, risks and costs were extracted. The prevalence of CM use
      ranges between 27 and 100%. Users perceived complementary therapies as
      beneficial, however, no data exist to suggest that these treatments are
      specifically effective. They are generally perceived as 'safe', but there is
      evidence to suggest that risks do exist. The costs for complementary therapies
      seem to be high and financial exploitation of patients may not be infrequent. It
      is concluded that complementary therapies for HIV-infected/AIDS patients are
      popular. Their potential for doing either harm or good requires more detailed
      study.

PMID- 9175649
TI  - Management of HIV-related diarrhoea.

PMID- 9175650
TI  - Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment
      with azithromycin.
AB  - A pre-treatment and a 3-week post-treatment isolate of Neisseria gonorrhoeae from
      a 13-year-old boy treated with azithromycin in a single 1 g oral dose were
      characterized microbiologically. Both isolates were of the same serovar/auxotype
      (1B6/non-requiring) and had similar antibiograms apart from erythromycin and
      azithromycin: the pre- and post-treatment MICs (minimum inhibitory
      concentrations) were: 1 mg/L and 32 mg/L to erythromycin and 0.125 mg/L and 3
      mg/L to azithromycin. The finding that both isolates were 1B6/NR, had similar
      antibiograms (other than azithromycin and erythromycin), and no other 1B6/NR
      isolates were resistant to erythromycin supports the view that macrolide
      resistance developed following treatment. A high overall level of azithromycin
      susceptibility was confirmed by testing 67 clinical isolates: MIC90 0.5 mg/L
      (range 0.023-0.75 mg/L). We conclude that the long half-life of azithromycin
      which is beneficial in treating chlamydial infection may result in increased
      selective pressure for resistance in gonococci. This report also highlights the
      importance of antibiotic susceptibility surveillance of gonococci and stresses
      the need for appropriate treatment of gonococcal infection, particularly when it
      is prescribed outwith departments of genitourinary medicine.

PMID- 9175651
TI  - Prevalence of sexual dysfunction in heterosexual patients attending a central
      London genitourinary medicine clinic.
AB  - Our objective was to determine the prevalence of sexual dysfunction among new
      heterosexual attendees at a central London genitourinary medicine (GUM) clinic.
      We carried out a cross-sectional study in which patients completed a self
      administered questionnaire-the Golombok-Rust Inventory of Sexual Satisfaction
      (GRISS) and participated in a brief interview during which additional information
      was sought regarding the patient's sexual history. An overall transformed score
      of >5 on the GRISS was defined as indicative of overall sexual dysfunction and a
      score of >5 on any of the subscales as indicative of a specific sexual
      dysfunction. Twenty-five (24%) men and 10 (9%) women had a GRISS score in keeping
      with overall sexual dysfunction, the prevalence being significantly lower in
      women (P=0.01, chi2=6.56, 1df). Sixty-three men (59%) and 63 (60%) women produced
      scores indicative of significant abnormality on at least one subscale, including,
      in men: erectile dysfunction 20 (19%), premature ejaculation 23 (22%), and in
      women: vaginismus 26 (25%) and anorgasmia 23 (22%). Neither an abnormal overall
      or subscale score on the GRISS was associated with a current STD on KC60
      diagnosis or a history of sexual assault for either men or women. There is a
      substantial prevalence of sexual dysfunction in new heterosexual attendees at our
      clinic, the service implications of which need to be addressed.

PMID- 9175652
TI  - Suppression of HIV replication in vitro by CD8+ T-cells from HIV-infected and HIV
      seronegative individuals.
AB  - The inhibitory effect of CD8+ T-cells from HIV-infected or HIV-seronegative
      individuals on HIV replication in the naturally-infected CD4+ T-cells in vitro
      was examined. Not only autologous CD8+ T-cells from HIV-infected individuals but
      also allogeneic CD8+ T-cells from HIV-seronegative individuals prevented or
      delayed HIV replication, even in transwell cocultures using a semi-permeable 0.45
      micron filter. The level of the inhibitory effect of allogeneic CD8+ T-cells from
      the HIV-seronegative individuals on the HIV replication was varied among CD4+ T
      cells obtained from HIV-infected individuals used. The results suggested that
      CD8+ T-cells from HIV-seronegative individuals as well as HIV-infected
      individuals could produce some cytokine(s) which suppress HIV replication in
      vitro. The sensitivity to the cytokine(s) might be variable among HIV strains,
      depending on differences in the nucleotide sequence of different HIV-1 strains.
      Further studies of control of HIV replication by CD8+ anti-HIV cytokine(s) should
      provide new strategies for the therapy of HIV infection.

PMID- 9175654
TI  - HIV seroprevalence amongst pregnant women in northeastern Zaire.
AB  - To assess the seroprevalence of HIV in pregnant women in northeastern Zaire and
      factors that correlate with seropositivity, sequential blood sampling and
      interviews were performed on 700 women at antenatal clinics in northeastern
      Zaire. The seroprevalence of the 3 clinics surveyed varied from 0.3%-5.5%, rates
      being higher in more urban areas. Seropositivity was associated with greater
      education (P<0.001) and having a partner whose job involved travelling (P<0.001).
      No correlation was found with marital status, age, or gravidity. Women in
      northeastern Zaire are at a greater risk of being infected with HIV if they are
      well educated or have a husband who travels due to his work. Health education on
      HIV should be particularly directed at women who are well educated and at men who
      have 'mobile' jobs.

PMID- 9175653
TI  - Gonorrhoea in Coventry 1991-1994: epidemiology, coinfection and evaluation of
      partner notification in the STD clinic.
AB  - The aim of this study is to analyse the epidemiology of gonorrhoea in the
      Coventry area between 1991-1994 and the implementation and outcome of partner
      notification. A total of 404 episodes in 382 patients comprised the study group.
      In Coventry, 97% of episodes were managed in the STD clinic. There was a decrease
      in female and heterosexual male cases from 172 cases in 1991 to 37 cases in 1994
      and increase in homosexual male cases from 8 in 1991 to 13 in 1994 (P<0.0001).
      Chlamydial coinfection was found in 38%. Among patients with gonorrhoea, 33% were
      asymptomatic and 40% with gonorrhoea and chlamydia were asymptomatic. Ten per
      cent of index cases were asymptomatic as were 83% of contact cases (P<0.0001).
      The health advisers (HAs) interviewed 82% immediately and 94% at some time after
      diagnosis. Of the average 1.5 partners per patient identified, 0.31 partners per
      patient were already screened, another 0.4 partners per patient were traced, 0.37
      partners per patient were not traced, and for 0.41 partners per patient
      notification outcome was unknown or unconfirmed. Partner notification of 278
      index cases traced 163 primary or tertiary contacts, 115 were new cases of
      gonorrhoea.

PMID- 9175655
TI  - Case management and patient reactions: a study of STD care in a province in
      Zambia.
AB  - Sexually transmitted disease (STD) case management was evaluated through
      observation and interviews at 2 urban and 4 rural health centres and 2 district
      hospital STD clinics in one urban and 2 rural districts in Central Province,
      Zambia. The analysis was limited to 59 patients (42 men and 17 women) who paid
      first visits for their disease and were managed by a clinical officer. The
      evaluation suffered from the lack of a standard for case management. Results
      showed that the patients engaged in risky sexual behaviour without being aware of
      the risks. At the health institutions, few patients were informed about condoms,
      the risk of HIV, and abstinence from sex during treatment and few were asked to
      notify their partners. Clinical officers with special STD training performed
      better than others but sill informed only one-fifth of the patients. Few clinical
      officers managed patients according to the syndromic approach recommended by the
      STD control programme.

PMID- 9175656
TI  - Silent upper genital tract chlamydial infection and disease in women.
AB  - To find what proportion of women with endocervical Chlamydia trachomatis
      infection had asymptomatic infection of the upper genital tract, 10 women with
      neither gonorrhoea nor signs, symptoms or a past history of pelvic inflammatory
      disease were laparoscoped. Swabs from the fimbriae and pouch of Douglas were
      tested for C. trachomatis by tissue culture, enzyme immunoassay, direct
      fluorescent antibody and polymerase chain reaction techniques. Four of the women
      had an upper genital tract chlamydial infection. Neither laparoscopic
      appearances, menstrual phase, interval since last intercourse, partner change nor
      other coincidental genital infection was associated with the upper genital tract
      spread. These findings suggest that careful investigation, immediate treatment
      and contact tracing are mandatory when asymptomatic endocervical chlamydial
      infection is discovered.

PMID- 9175657
TI  - History of sexual abuse among HIV-infected women.
AB  - The objective of this study is to describe the characteristics associated with a
      history of sexual abuse among HIV-infected women enrolled in a public inner-city
      HIV outpatient clinic. A retrospective chart review of 238 women of childbearing
      age enrolled in the HIV outpatient clinic between 1987 and 1995 was performed.
      Characteristics of the study population were 83% African American, 69% single,
      and 53% finished high school or were still in school. The mean age was 25.7
      years. Of the 238 women, 32% had a history of sexual abuse. Factors associated
      with sexual abuse history after controlling for age included living in a non
      permanent situation (OR=4.8), history of non-intravenous drug use (OR=4.65), and
      having dropped out of school (OR=2.2). HIV-infected women should be screened for
      a history of sexual abuse and carefully counselled regarding their reproductive
      choices and drug treatment.

PMID- 9175658
TI  - The sexual behaviour of international travellers at two Glasgow GUM clinics.
      Glasgow genitourinary medicine.
AB  - A survey of patients attending 2 Glasgow genitourinary medicine (GUM) clinics was
      conducted in 2 3-month periods in 1993 and 1994. Three hundred and twenty-five
      attendees who had travelled abroad in the preceding 3 months completed anonymous
      self-administered questionnaires about their sexual behaviour during these recent
      journeys abroad. There were 112 women and 213 men (185 heterosexuals and 28
      homosexuals). Twenty-two (19.6%) women, 56 (31%) heterosexual men and 13 (42%)
      homosexual men had a sexual contact with a new partner while abroad. Of those who
      had had a new sexual contact abroad, 11 women (50% of those who had sex with a
      new partner) and 33 heterosexual men (59% of those who had sex with a new
      partner) were inconsistent users of condoms. Analysis of data found that
      homosexual and heterosexual men, and business travellers, are at increased risk
      of exposure to sexually transmitted diseases, including HIV infection, and should
      be targeted with safer sex health promotion prior to travel.

PMID- 9175659
TI  - Cryptosporidiosis in patients with AIDS.
AB  - Cases of cryptosporidiosis in patients with the acquired immunodeficiency
      syndrome (AIDS) residing in Melbourne over a 6-year period (1990-1995) are
      described. During this period 85 cases occurred, while 979 new AIDS diagnoses
      were notified. Over this period temporal clustering in cryptosporidial detection
      was evident (P=0.007), but the pattern was not statistically associated with the
      season, rainfall (P=0.88), mean average maximal temperature (P=0.15) or mean
      average minimal temperature. Further studies should identify these risk factors
      and provide an opportunity to prevent this devastating disease.

PMID- 9175660
TI  - Splenic pneumocystosis in AIDS: unusual ultrasound appearances.

PMID- 9175661
TI  - How successful are we in administering prophylaxis against Pneumocystis carinii
      pneumonia (PCP) in patients with HIV infection?

PMID- 9175662
TI  - AGUM meeting on Outreach Services in Genitourinary Medicine. Association of
      Genito-Urinary Medicine.

PMID- 9175663
TI  - A WHO collaborative study of maternal anthropometry and pregnancy outcomes.
AB  - OBJECTIVES: To evaluate to what degree anthropometric measurements are useful and
      efficient in predicting maternal and fetal outcomes in different country settings
      and to develop appropriate reference curves for maternal weight gain. METHODS: A
      meta-analysis of 25 data sets providing information on over 111000 births
      worldwide. RESULTS: Attained weight indicators from pre-pregnancy (Pp) through 9
      lunar months demonstrated high odds ratios (O.R.) for both low birth weight (LBW)
      and intra-uterine growth retardation (IUGR). The strongest effect size (O.R. =
      4.0) was provided by attained weight at 7 lunar months for IUGR, when applied to
      women of below average pre-pregnancy weight. The study indicators showed only
      minor and inconsistent O.R. for preterm birth (PTB). The ability of study
      indicators to predict the three maternal outcomes was much weaker. Maternal
      height as a predictor of assisted delivery showed the highest positive O.R.
      (1.6), but did not meet the screening criteria. CONCLUSIONS: A single measurement
      of attained weight at 5 or 7 lunar months (16-20 or 24-28 weeks) is the most
      practical screening instrument for LBW and IUGR in most primary health care
      settings and provides warning of the need for intervention. The operational value
      of these findings should be demonstrated through their successful large-scale
      application in service settings.

PMID- 9175664
TI  - Superficial wound disruption after cesarean delivery: effect of the depth and
      closure of subcutaneous tissue.
AB  - OBJECTIVE: The aim of this study was to determine the effect of the depth of
      subcutaneous tissue at the operative site and the closure of subcutaneous tissue
      on abdominal wound disruption after cesarean delivery. METHODS: 164 women divided
      into two groups: 70 with subcutaneous tissue thickness of at least 2 cm and 94
      with subcutaneous tissue thickness more than 2 cm. These groups were randomized
      to closure of the subcutaneous fat tissue or no closure with cesarean delivery.
      RESULTS: In the 68 women with subcutaneous tissue thickness of at least 2 cm who
      completed the study, there was no difference between closure and no closure
      subgroups in terms of incidence of wound disruption. In 91 women with
      subcutaneous tissue thickness more than 2 cm who completed the study, the
      incidence of wound disruption was significantly higher in the no closure
      subgroup. In the no closure subgroup of 91 women with subcutaneous fat thickness
      more than 2 cm, the incidence of wound disruption was significantly higher than
      that of the 68 women with subcutaneous tissue thickness at least 2 cm.
      CONCLUSIONS: Subcutaneous tissue approximation with absorbable suture at closure
      of the abdominal incision during cesarean delivery appears to reduce the rate of
      postoperative wound disruption in patients with more than 2 cm of subcutaneous
      tissue.

PMID- 9175665
TI  - Complications of cervical cerclage in rural areas.
AB  - OBJECTIVE: To determine whether the outcome of pregnancies following cervical
      cerclage in rural Tanzania justifies its application in remote areas. METHOD:
      Retrospective review of 16 singleton pregnancies in 13 women, who underwent
      cervical cerclage in a rural hospital in Tanzania during 1990-1995. RESULTS: Ten
      (62.5%) live children were born. Seven women (43.8%) delivered after a
      gestational age of 37 weeks. Severe maternal complications were encountered 5
      times (31.3%): 4 severe cervical lacerations and 1 uterine rupture. CONCLUSION:
      One should be reluctant to apply cervical cerclage in remote rural areas due to
      the high rate of maternal complications, as patients' delay in reaching the
      hospital may be considerable in cases of preterm birth.

PMID- 9175666
TI  - Third-trimester maternal serum beta-HCG level and umbilical blood flow in fetal
      growth retardation.
AB  - OBJECTIVE: To determine the relationship between maternal serum beta-HCG level
      and umbilical artery systolic/diastolic ratio in fetal growth retardation.
      METHODS: Maternal serum beta-HCG was measured in 57 pregnant women in the third
      trimester, 31 with a fetal growth retardation and 26 with a normal growth. The
      systolic/diastolic ratio was measured in a midsection of the umbilical cord the
      same day of the biochemical determination. RESULTS: The serum beta-HCG level was
      statistically significant higher in pregnant women with a fetal growth
      retardation associated with a high systolic/diastolic ratio (n = 9) (P < 0.001).
      There were no differences between the fetuses with a normal growth (n = 26) and
      those with an intrauterine growth retardation and a normal systolic/diastolic
      ratio (n = 22). There was a significant positive correlation between maternal
      serum beta-HCG level and umbilical artery systolic/diastolic ratio (P < 0.01).
      CONCLUSION: Fetal growth retardation due to Doppler-defined vascular placental
      insufficiency is associated with a higher maternal serum beta-HCG level.

PMID- 9175667
TI  - Evaluation of interobserver agreement of cardiotocograms.
AB  - OBJECTIVE: To evaluate interobserver agreement in visual analysis of each
      cardiotocographic event. METHODS: Three experts independently divided 16
      antepartum and 17 intrapartum cardiotocograms into baseline segments,
      accelerations and decelerations, according to the FIGO guidelines. Baseline
      segments were further classified as having normal, reduced or increased
      variability and decelerations as early, late and variable. Uterine activity was
      divided into tonus and contractions. Agreement was assessed by the proportions of
      agreement (pa) with 95% confidence intervals. RESULTS: Reproducibility in
      assessment of baseline segments with normal variability, accelerations and
      uterine activity was acceptable (pa = 0.56-0.71) whereas that of other segments
      was not (pa = 0.14-0.45). CONCLUSIONS: Analysis of most cardiotocographic events
      is poorly reproducible, even when experts use the FIGO guidelines. This may be
      explained by some still ambiguous guidelines, by eyeball limitations in
      evaluation of subtle events, and by the incapacity of busy clinicians to assess
      complex and multiple cardiotocographic events in a systematic and disciplined
      fashion.

PMID- 9175669
TI  - Calcium-phosphorus-magnesium homeostasis in women with threatened preterm
      delivery.
AB  - OBJECTIVE: The effect of threatened preterm delivery on calcium, phosphorus,
      magnesium homeostasis in the third trimester of pregnancy was investigated.
      METHODS: Serum concentrations of total and ionized calcium, inorganic phosphorus,
      magnesium, total protein, albumin, total estrogens and human placental lactogen
      were determined in women with threatened preterm delivery at 29-36 weeks of
      gestation (the studied group) and in women with uncomplicated pregnancy of the
      same duration (the control group). Additionally, activities of total alkaline
      phosphatase and heat-stable alkaline phosphatase fraction were measured. RESULTS:
      Patients of the studied group compared to the control group showed decreased
      concentration of total calcium (2.17 +/- 0.09 vs. 2.28 +/- 0.13 mmol/l, P <
      0.0005), inorganic phosphorus (1.13 /- 0.27 vs. 1.32 +/- 0.23 mmol/l, P < 0.001)
      and magnesium (0.64 +/- 0.07 vs. 0.70 +/- 0.10 mmol/l, P < 0.003); they also
      demonstrated decreased activity of total alkaline phosphatase (70.8 +/- 23.2 vs.
      81.9 +/- 14.9 IU/l, P < 0.01) and its heat-stable fraction (30.2 +/- 15.6 vs.
      59.6 +/- 14.9 IU/l, P < 0.001). In the studied group no difference was found in
      concentrations of investigated ions and enzymes between women who delivered at
      term and women who delivered prematurely. Patients with threatened preterm
      delivery showed serum deficiency of total calcium, phosphorus and magnesium which
      might be related to premature uterine contractility but does not predict
      premature labor by week 36 of gestation (66% of patients delivered at term).
      CONCLUSION: The deficiency of minerals and lowered activity of total alkaline
      phosphatase is observed in women with threatened preterm delivery. Laboratory
      tests of calcium-phosphorus-magnesium homeostatsis have limited predictive value
      in regard to the term of delivery in women with threatened preterm delivery.

PMID- 9175670
TI  - Simple ovarian cysts in premenopausal patients.
AB  - OBJECTIVE: To compare clinical, ultrasonographical, and cytological findings with
      the histopathological diagnosis of unilocular, anechoic smooth-walled cystic
      ovarian tumors ('simple ovarian cysts'). METHOD: In 140 premenopausal women
      simple ovarian cysts were removed by laparoscopy following ultrasound evaluation.
      In this retrospective study the histopathological diagnosis was correlated with
      clinical data, sonographic characteristics, macroscopic impression and with
      cytological findings. RESULTS: Histopathology revealed 21 (15.0%) functional
      cysts, 31 (22.1%) retention cysts, 9 (6.4%) endometriomas, 3 (2.1%) cystic
      teratomas, 12 (8.6%) undifferentiated cysts and 64 (45.7%) cystadenomas. No
      mentionable differences were correlated with the patient's age or the size of the
      cyst as determined by ultrasound. Classically, 'chocolate-like' cystic fluid
      characterizes endometriomas. However, in the present study cysts with different
      histopathological classifications exhibited similar fluid characteristics. The
      cytological diagnosis was correct in only 53 (37.9%) of all 140 cases.
      CONCLUSION: In premenopausal women differential diagnosis of ovarian cysts is not
      possible by clinical characterization, either by ultrasound or cytological
      evaluation. Simple ovarian cysts should be observed for at least 8 weeks or 2
      menstrual cycles, respectively. If persisting over that period, the ovarian cyst
      should be removed by laparoscopy, but not by cyst aspiration.

PMID- 9175671
TI  - Synthetic sling for genital prolapse in young women.
AB  - OBJECTIVE: The aim is to repair uterine prolapse in young women, utilizing
      synthetic tape (Merselene). It is a prospective study demonstrating an operative
      procedure for correction of uterine prolapse in young women. This procedure was
      performed in three post-graduate teaching hospitals: Institute of Obstetrics and
      Gynaecology, Gandhi Hospital and Niloufer Hospital, Hyderabad, India. METHOD:
      Through an abdominal approach, the Merselene tape was fixed on the posterior
      surface of the uterus and anchored to the anterior longitudinal ligament, over
      the sacral promontory. This procedure was performed on 19 women in the age group
      17-27 years, two of whom were unmarried virgins. RESULTS: The procedure rectified
      the descent of the uterus and kept it anteverted. In one of the cases,
      exploration at cesarean section showed that the sling was intact. There were no
      significant intraoperative or postoperative complications. Recurrence of prolapse
      was not reported in any of these cases. CONCLUSION: This technique is a
      relatively simple method for correction of uterine prolapse in young women. The
      Merselene tape is inert, strong, flexible, effectively supports the uterus, and
      remains retroperitoneal.

PMID- 9175668
TI  - Preeclampsia, labor duration and mode of delivery.
AB  - OBJECTIVE: To determine if there is a difference in the length of labor, and
      method of delivery between preeclamptic and normotensive patients. METHODS: A
      retrospective case control study was performed using a perinatal database. Study
      subjects included nulliparous patients diagnosed with preeclampsia, and were
      compared with normotensive nulliparous patients. RESULTS: There were 1454
      controls and 727 subjects identified. There was no difference between groups with
      regard to duration of total labor. There was a statistically but not clinically
      significant increase in the duration of the second stage in preeclamptics (35 vs.
      27 min, P = 0.003). Preeclamptics had a consistently higher risk of cesarean
      delivery, even when controlled for confounding variables. CONCLUSION: The
      clinical belief that preeclamptic patients have more rapid labors is not
      supported. Preeclamptics do seem to have a higher risk of cesarean delivery.

PMID- 9175672
TI  - Maternal mortality due to obstructed labor.

PMID- 9175673
TI  - Obstetric determinants of low Apgar scores in a Chinese population.

PMID- 9175674
TI  - Age of natural menopause among women in Lima City, Peru.

PMID- 9175675
TI  - ACOG educational bulletin. Human immunodeficiency virus infections in pregnancy.
      American College of Obstetricians and Gynecologists.

PMID- 9175676
TI  - ACOG educational bulletin. Teratology. American College of Obstetricians and
      Gynecologists.

PMID- 9175677
TI  - ACOG committee opinion. Rate of vaginal births after cesarean delivery. Number
      179, November 1996. Committee on Obstetric Practice. American College of
      Obstetricians and Gynecologists.

PMID- 9175678
TI  - Primary-preventive care criteria set: office review of patient immunization
      status. Number 19, November 1996. Committee on Quality Assessment. American
      College of Obstetricians and Gynecologists.

PMID- 9175679
TI  - Ambulatory care criteria set: intervention for domestic violence. Number 20,
      November 1996. Committee on Quality Assessment. American College of Obstetricians
      and Gynecologists.

PMID- 9175680
TI  - Report of the FIGO Committee for the Study of Ethical Aspects of Human
      Reproduction. International Federation of Gynecology and Obstetrics.

PMID- 9175681
TI  - Survey of obstetricians' personal preference and discretionary practice.
AB  - OBJECTIVE: To determine obstetricians personal choices in relation to Down
      syndrome screening and mode of delivery for themselves or their partners. STUDY
      DESIGN: Structured anonymous postal survey. All 282 obstetric consultants, senior
      registrars and registrars in NHS obstetric units within London's M25 region were
      surveyed. RESULTS: The response rate was 73% (206). Fifty one per cent (105)
      chose to have elective amniocentesis/CVS without a previous screening test when
      maternal age was > or = 35 years and 11% (23) when < 35 years. Of the remainder,
      the majority wanted both maternal serum screening and nuchal translucency rather
      than a single screening test. In relation to mode of delivery, 17% (33) of
      obstetricians chose elective caesarean section (CS) in the absence of any
      clinical indication. Of those who chose CS, 88% did so out of fear of perineal
      damage. However when faced with a mid-cavity instrumental delivery in the second
      stage, only 5% (8) wanted CS, the remainder choosing operative vaginal delivery.
      With an uncomplicated breech presentation, only 27% (55) opted for external
      cephalic version while 57% (114) chose elective CS. CONCLUSION: This study
      demonstrates interventionist attitudes among a sizeable percentage of
      obstetricians in relation to antenatal screening and their own preferred mode of
      delivery. It suggests that obstetricians regard management options not normally
      available to pregnant women as valid choices for themselves or their partners.

PMID- 9175682
TI  - A plan for the future of obstetrics and gynaecology in Europe.

PMID- 9175683
TI  - Nicardipine versus salbutamol in the treatment of premature labor. A prospective
      randomized study.
AB  - OBJECTIVE: To compare the tocolytic action and the side effects of nicardipine to
      those of salbutamol in patients presenting premature labor in order to propose
      nicardipine as a promising alternative to salbutamol in the treatment of
      premature labor. STUDY DESIGN: Ninety patients admitted to the Saint-Antoine
      Hospital (Paris, France) for premature labor were included in this prospective
      randomized open study comparing nicardipine and salbutamol. Each study group
      included 45 patients. RESULTS: The mean term of delivery in the nicardipine group
      was 38.4 +/- 1.7 and 37.6 +/- 2.1 weeks in the salbutamol group (P < 0.05). The
      percentage of deliveries after 37 gestational weeks was higher with nicardipine
      (P < 0.05). The birthweight of infants was 3131 +/- 488 g with patients treated
      with nicardipine and 3019 +/- 494 g with the salbutamol group (NS). The Apgar
      scores were identical in the two groups at 1 and 5 min. There was no
      statistically significant difference in the number of neonates admitted into
      intensive care nor the premature infant center between the two groups.
      Nicardipine reduced the systolic and diastolic blood pressure whereas there was
      no change in the salbutamol group. Maternal pulse rate was significantly
      increased in the salbutamol group (P < 0.01) and was unchanged in the nicardipine
      group. The most common side-effects with nicardipine were headaches, and with
      salbutamol, tremors and palpitations. CONCLUSIONS: Nicardipine is a tocolytic
      agent as effective as salbutamol in the treatment of premature labor. The use of
      nicardipine is an interesting alternative to salbutamol, especially in cases of
      hypertension, diabetes or maternal cardiopathy.

PMID- 9175684
TI  - Plasma interleukin-1alpha, interleukin-1beta and interleukin-1 receptor
      antagonist levels in pre-eclampsia.
AB  - The values of plasma interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta)
      and interleukin-1 receptor antagonist (IL-1ra) levels were evaluated as the
      markers of pre-eclampsia in 35 serial plasma samples from ten pregnant women who
      subsequently developed pre-eclampsia and in 74 plasma samples from 20
      uncomplicated pregnancies, retrospectively. No correlation was found between
      plasma IL-1alpha, IL-1beta and IL-1ra levels, liver and renal function tests,
      thrombocyte and white blood cell counts, proteinuria, systolic and diastolic
      blood pressures and gestational weeks. Almost equal levels of IL-1alpha and IL
      1beta were measured in all corresponding groups, but these were too few in number
      to statistically analyze. IL-1ra values were higher in the pre-eclampsia group
      than in the uncomplicated pregnancy group, at 20-25 and 31-35 gestational weeks
      significantly and 26-30 gestational weeks insignificantly and showed an increase
      during labor in both groups. It was found to have 58% positive predictivity, 100%
      negative predictivity, 50% specificity and 100% sensitivity at gestational weeks
      20-25. According to these results, IL-1ra seems to be considered for its high
      negative predictivity in the exclusion of the probability of pre-eclampsia
      development during antenatal visits, but its plasma level is not correlated with
      the severity of the disease.

PMID- 9175685
TI  - Association between a low umbilical artery pulsatility index and fetal distress
      in labor in very prolonged pregnancies.
AB  - OBJECTIVE: To investigate the association between fetal, umbilical and uterine
      circulatory changes and adverse perinatal findings in very prolonged pregnancies.
      STUDY DESIGN: 44 women proceeding to 43 completed weeks of gestation with the
      intention of a trial of vaginal delivery were studied prospectively with
      ultrasound Doppler velocimetry. An intensified fetal surveillance was routinely
      commenced at 42 weeks and only uncomplicated pregnancies were allowed to proceed.
      The endpoint perinatal measures were oligohydramnios, fetal meconium release,
      fetal distress in labor and birth asphyxia. Flow variables in different groups
      were compared with the Mann-Whitney U test, Student's unpaired t-test, Wilcoxon
      signed-rank matched-pairs test, Fisher's exact test and contingency table
      analysis, and a two-tailed P value <0.05 was considered statistically
      significant. RESULTS: The umbilical artery pulsatility index was significantly
      lower in cases of fetal meconium release (n=12) and fetal distress (n=7). The
      umbilical venous flow velocity was significantly lower in cases of meconium, and
      the fetal aortic volume flow significantly higher in cases of fetal distress. No
      significant flow changes were found in connection with oligohydramnios (n=5) and
      birth asphyxia (n=2). Uterine flow was not significantly affected in any group.
      CONCLUSIONS: In very prolonged pregnancies, fetal distress in labor was not
      associated with an increased placental vascular resistance. In contrast to
      previous reports, the umbilical artery pulsatility index was low in cases of
      fetal distress and meconium release. The etiology is unknown, but a subclinical
      fetal hypoxia might have triggered a vasodilation of placental vessels.
      Vasodilation at an unchanged volume flow could also explain the decrease of
      umbilical venous flow velocity. The increased aortic volume flow indicates an
      increase of cardiac output in fetuses later developing distress in labor.

PMID- 9175686
TI  - Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of
      procoagulants and reduced levels of inhibitors during pregnancy induce a
      hypercoagulable state, combined with a reactive fibrinolysis.
AB  - OBJECTIVE: To establish the physiologic changes in the coagulation and
      fibrinolytic systems during normal pregnancy and puerperium. STUDY DESIGN: One
      hundred and seventeen normal pregnant women were investigated in a longitudinal
      study involving five measurements: blood samples were collected at 10, 20, 30, 36
      weeks and on the second day puerperium and were assayed for prothrombin time (PT
      expressed in INR), activated partial thromboplastin time (PTT), fibrinogen (FBG),
      antithrombin III activity (AT III), protein C activity (PC), protein S activity
      (PS), prothrombin fragments 1+2 (F1+2), type 1 plasminogen activator inhibitor
      activity (PAI) and tissue-plasminogen activator antigen (t-PA). Student t-test,
      One Way Analysis of Variance (ANOVA) and Bonferroni test were used for
      statistical analysis. P<0.05 (two tails) was assumed to indicate a significant
      difference. RESULTS: Fibrinogen concentrations were always increased with respect
      to controls (P<0.001), while protein S was always decreased, with values
      averaging 60% of those of controls from the 10th week of pregnancy onwards
      (P<0.001). Variance analysis showed a statistically significant increase with
      gestational age for procoagulant factors (INR: P<0.001; FBG: P<0.001), a
      reduction for anticoagulants (PC: P<0.0001; PS: P<0.0001), and a rise for F1+2
      (P<0.0001). With regard to fibrinolysis, there was an increase both for t-PA
      (P<0.0001) and PAI-1 (P<0.0001) during pregnancy. The t-PA values were always
      comprised in the normal range. PAI-1 were increased with respect to control
      values starting from 31st week. The most significant variations in the
      procoagulants (expressed by PT and FBG) were recorded up to the 20th week
      (P<0.001); from the 30th week onwards, they remained stable until after the
      delivery. The same was true for protein S levels (P<0.001), except that the
      difference between the 10th and the 20th weeks was not statistically significant.
      The level of F1+2 gradually increased throughout pregnancy (P<0.001), and then
      fell in the puerperium (P<0.001). CONCLUSIONS: The parameters showing the
      greatest variation during pregnancy were PT, FBG, PS, F1+2 and PAI-1. The
      existence of a hypercoagulable state in pregnancy was suggested by the increased
      levels of F1+2.

PMID- 9175687
TI  - Anti-beta 2 glycoprotein I antibodies in a general obstetric population:
      preliminary results on the prevalence and correlation with pregnancy outcome.
      Anti-beta2 glycoprotein I antibodies are associated with some obstetrical
      complications, mainly preeclampsia-eclampsia.
AB  - OBJECTIVE: To evaluate the prevalence in normal pregnancies of anti-32
      glycoprotein I (anti-beta2GPI) antibodies, and their association with obstetrical
      complications. STUDY DESIGN: Prospective study of anti-beta2GPI and
      anticardiolipin (CL) antibodies in 510 healthy pregnant women at 15-18 weeks.
      According to the results, women were categorized into three groups: group I,
      negative for both antibodies; group II, positive for anti-beta2GPI antibodies;
      group III, positive for aCL only. The rates of fetal loss, abruptio placentae,
      preeclampsia-eclampsia, and fetal growth retardation were compared in the three
      groups. RESULTS: Anti-beta2GPI antibodies were found in 20 women (3.9%) and aCL
      in 8 patients (1.6%). Obstetrical complications were more frequent, even if not
      significantly different, in group II, 15%, than in group I, 4.1% (difference
      10.9%; 95% confidence interval (CI): 1.6-20.2%; p=0.0575), while no complications
      were seen in group III. Preeclampsia-eclampsia were significantly more frequent
      in group II (10%) than in group I (0.8%; difference 9.2%; 95% CI: 4.4-14%;
      p=0.021). The prevalence of fetal growth retardation was not significantly
      different in the two groups (5% vs. 2%, respectively). COMMENT: Our findings
      indicate that anti-beta2GPI antibodies are associated with some obstetrical
      complications, mainly preeclampsia-eclampsia, even if more conventional
      antiphospholipid antibodies are not present. This observation suggests that these
      antibodies should be investigated in such cases, in order to improve the outcome
      of subsequent pregnancies, as well as in women with a history of early and/or
      recurrent severe preeclampsia in order to start a prophylactic treatment (i.e.
      low-dose aspirin or heparin).

PMID- 9175688
TI  - Salpingo-oophorectomy for adnexal masses. Place and results for operative
      laparoscopy.
AB  - OBJECTIVES: The aim of the study is to specify the place, modalities and results
      of operative laparoscopy when adnexectomy is indicated in a patient presenting
      with an adnexal mass. STUDY DESIGN: A retrospective analysis of the 186 patients
      who underwent adnexectomy for an adnexal mass between January 1, 1989 and
      December 31, 1994. RESULTS: The operation took place via laparotomy in 34.9% of
      cases (65 patients) and by laparoscopic surgery in 65.1% of cases (121 patients).
      All the patients presenting a malignant ovarian lesion (15 cases) were operated
      by laparotomy. For these patients the laparotomy was decided from the outset in 7
      cases and there was a conversion to laparotomy decided during the diagnostic
      phase of laparoscopy in 8 cases. The preoperative workup (clinical examination,
      study of past history, trans vaginal ultrasonography, doppler, tumoral markers
      etc.) together with the diagnostic phase of laparoscopy provide 100% sensitivity,
      a positive predictive value of 50% and a negative predictive value of 100% for
      diagnosis of malignancy. CONCLUSION: These results demonstrate that provided a
      strict selection system is used, it is possible to carry out adnexectomy using
      laparoscopic surgery in 70.8% of cases (121/171) for patients with benign adnexal
      mass.

PMID- 9175689
TI  - Changes in ultrasound appearance of the internal female genital organs during
      treatment for eating disorders.
AB  - OBJECTIVE: To confirm that changes of the internal female genital organs in
      patients with eating disorders can be detected with ultrasound and that
      successive normalization can be followed during treatment. STUDY DESIGN: Thirty
      five women with the diagnoses of eating disorders were examined with ultrasound
      while undergoing psychiatric treatment. The endometrial thickness and ovarian
      volume were measured. The sonographic picture of the ovaries was classified in
      four classes. RESULTS: Bulimics had changes of their ovaries in spite being of
      normal weight. After psychiatric treatment and a normal diet, the ovaries and the
      bleeding pattern normalized without a change in body weight. In anorectics,
      undetectable ovaries or ovaries without follicles were associated with low body
      mass index (BMI), but multifollicular ovaries or presence of a dominant follicle
      and ovarian volume had no clear relation to BMI. The endometrial thickness
      correlated with BMI. CONCLUSION: Ovarian morphology appeared more important than
      ovarian size. Changes of the ovaries appeared more related to eating patterns
      than to BMI. Eating disorders should be considered in women with bleeding
      disorders. Ultrasound examination can contribute to the differential diagnosis.

PMID- 9175690
TI  - Clinical and immunological condition of newborns of mothers treated for recurrent
      spontaneous abortions with paternal lymphocytes immunization.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical condition at birth
      and some laboratory parameters in newborns of mothers treated for recurrent
      spontaneous abortion (RSA) of unknown etiology with paternal lymphocytes
      immunization. STUDY DESIGN: The study comprised 104 newborns delivered by 102
      women with RSA, who underwent alloimmunization and 90 randomly chosen control
      newborns. The following parameters were analysed in two groups of newborns:
      general condition at birth, physical development, course of adaptation period,
      values of hematological and immunological (percentage of CD3, CD4, CD8, CD19 and
      CD3/CD25 lymphocytes, chemiluminescence of neutrophils at rest and stimulated
      with opsonized zymosane) parameters in umbilical arterial blood. RESULTS: No
      statistically significant differences were noted between the two groups of
      newborns as to the duration of pregnancy, birth weight, general condition at
      birth, occurrence of complications in the adaptation period and values of studied
      hematological and immunological parameters. CONCLUSION: These results suggest
      that immunization with paternal lymphocytes in women with RSA of unknown etiology
      not only creates better prognosis for the outcome of the pregnancy, but is also
      safe for the fetus and the newborn.

PMID- 9175691
TI  - Predicting optimal cervical mucus for infertility diagnosis.
AB  - OBJECTIVE: We studied the relationship between cervical mucus evaluations and
      daily fertility examinations in order to find monitoring techniques that can
      predict optimal mucus one day before it occurs. METHODS: Twenty-three healthy
      young female volunteers were followed during one spontaneous cycle with serial
      measurements of serum estradiol, progesterone, LH and FSH, urinary LH, and
      transvaginal ultrasound measurements of endometrial thickness and follicles. Data
      were related to cervical mucus scores. RESULTS: All cycles were ovulatory with
      optimal mucus, but in 14 optimal mucus was present for only one day. Echographic
      measurement of the leading follicle (mean diameter > or = 18 mm) could predict
      the day of optimal mucus in 78% and estradiol (> 700 pmol/l) in 83% of the cases.
      These two measurements combined predicted optimal mucus in 100% of the
      investigated women one day in advance. CONCLUSION: Optimal cervical mucus
      parameters can be predicted one day in advance by serial measurements of serum
      estradiol and follicular diameters.

PMID- 9175692
TI  - Is it necessary to perform a prophylactic oophorectomy during hysterectomy?
AB  - OBJECTIVE: To evaluate the subsequent pelvic sonographic characteristics as well
      as the clinical outcome following hysterectomy with and without oophorectomy.
      STUDY DESIGN: A prospective study of sonographic evaluation of 164 women, aged 29
      72 years, with a history of hysterectomy was performed. Ninety-one patients
      underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and
      73 women had either hysterectomy (abdominal or vaginal) only or hysterectomy with
      unilateral salpingo-oophorectomy. RESULTS: The mean time interval between surgery
      and sonographic evaluation was 4.3 years (range, 1-25 years). Out of the 73 women
      with left ovaries, 37 (50.7%) were found to have pelvic lesions and four women
      underwent re-operations following these findings. The histologic finding were
      cystadenoma, hydrosalpinx with periovarian adhesions and two paraovarian cysts.
      In comparison, only five of the 91 women (5.5%) following bilateral salpingo
      oophorectomy were found to have pelvic lesions (P < 0.0005). None of the women
      with prophylactic oophorectomy were operated upon following these findings.
      CONCLUSIONS: In comparison to patients after total hysterectomy and bilateral
      salpingo-oophorectomy, women with prior hysterectomy and ovarian preservation are
      prone to subsequent pelvic lesions. They need to be closely followed with
      clinical, laboratory and sonographic means, and may undergo reoperations in order
      to rule out the possibility of neoplasia.

PMID- 9175693
TI  - Laparoscopic fimbrioplasty and neosalpingostomy. Experience of the Yaounde
      General Hospital, Cameroon (report of 194 cases).
AB  - OBJECTIVE(S): To study the fertility results after laparoscopic distal tuboplasty
      and compare them with the data in the literature. STUDY DESIGN: 194 laparoscopic
      distal tuboplasties were carried out from May 1992 to May 1994 in the Yaounde
      General Hospital (Cameroon). The results were analysed according to the age of
      the patients, the type and duration of infertility, past history of abortion,
      laparotomy and Chlamydia trachomatis infection, the tube and adhesion scores,
      surgical procedures and achievement of pregnancy. The fertility rates were
      calculated according to Cramer's method [11]. The cumulative pregnancy rate
      curves were drawn up from the life table [12] and compared using the Log-Rank
      test. RESULTS: 53 patients obtained pregnancy (27.3%) of which 45 were inter
      uterine (23.2%) and 8 ectopic (4.1%). Of the 45 intra-uterine pregnancies (IUP),
      36 were obtained after fimbrioplasty (33.3%) and 9 after neosalpingostomy
      (10.5%). The monthly fertility rate at one year was 1.4%. The rate of IUP for
      tube stages I and II is significantly higher than that for stages III and IV
      (p<0.001). However the rate of ectopic pregnancies (EP) is proportional to damage
      to the tubes. Infection with Chlamydia trachomatis, and residual inflammation
      could have an effect on the achievement of pregnancy. CONCLUSION(S): Our results
      are similar to those found in the literature. The tube stage thus remains the
      decisive factor in terms of fertility (Cox: p<0.001). Operative laparoscopy is
      the best alternative in our countries compared with laparotomy for distal tubal
      pathology.

PMID- 9175694
TI  - Inter-alpha-trypsin inhibitor is concentrated in the pericellular environment of
      mouse granulosa cells through hyaluronan-binding.
AB  - OBJECTIVE: The binary complex involving hyaluronan and inter-alpha-trypsin
      inhibitor (ITI) is an important component of the cumulus oocyte complex. The aim
      of this study is to investigate the physiological association between ITI and its
      derivatives and hyaluronan or its binding protein (HABP). STUDY DESIGN: ITI and
      its derivatives (heavy chains of ITI and urinary trypsin inhibitor, UTI) were
      tested for their ability to interact with hyaluronan or HABP. HABP was used to
      locate the distribution of hyaluronan in mice ovaries. RESULT: ITI and heavy
      chains of ITI, but not UTI, could specifically bind to immobilized hyaluronan.
      Furthermore HABP could specifically bind immobilized hyaluronan with high
      affinity, and also to immobilized ITI and its derivatives. 6 h after the
      injection of human chorionic gonadotropin, the hyaluronan staining in the
      preovulatory ovaries displayed a heterogenous appearance in which the most
      intense stainings were observed in cumulus oocyte complex. The distribution of
      ITI was found to be similar to that of hyaluronan. CONCLUSION: The hyaluronan
      binding sites of ITI are located in the heavy chains of this molecule. ITI is
      concentrated in the pericellular environment of granulosa cells through
      hyaluronan-binding. The altered amount of hyaluronan and ITI in the preovulatory
      ovaries may contribute to their important clinical characteristics including
      cumulus oocyte complex expansion.

PMID- 9175695
TI  - Electrohysterogram: study of the electromechanical activity of the uterus in
      humans.
AB  - The electromechanical activity of the uterus was studied in 18 healthy women
      (mean age 38.3+/-14.2 SD years; 8 were nulliparous, 10 multiparous) aiming at
      characterizing a normal electrohysterogram. Two monopolar silver-silver chloride
      electrodes were applied to the uterine and one to the cervical mucosa. The
      uterine pressure was measured by a water-perfused tube connected to a pressure
      transducer. Monophasic, negatively deflected slow waves or pacesetter potentials
      (PPs) were recorded from the 2 uterine electrodes. They had regular rhythm and
      exhibited the same frequency, amplitude and velocity of conduction by the 2
      electrodes. The PPs were followed randomly by bursts of action potentials (APs).
      The APs and not the PPs were associated with uterine pressure rise. PPs from the
      cervix were registered only occasionally. The occurrence of the electric activity
      is believed to depend on the smooth muscle fibers content which is high in the
      uterine body and meagre in the cervix. The APs seem to have contractile activity
      which might act to sweep away the uterine secretions. According to the
      uterocervical reflex, the cervix dilates upon uterine contractions. A normal
      electrohysterogram could be characterized. It might show a different pattern in
      the various uterine pathologic conditions and may thus represent an investigative
      tool in the diagnosis of such disorders.

PMID- 9175696
TI  - Mast cells in cervical ripening--an immunohistochemical and biomechanical study
      in rats.
AB  - Cervical ripening purportedly involves different cell types and mediators
      normally associated with inflammatory reactions. The purpose of the present study
      was to determine the presence of mast cells in rat cervices during spontaneous
      and antigestagen induced ripening and to test whether a mast cell stabilizer was
      able to inhibit the antigestagen induced cervical ripening. Immunohistochemical
      examinations demonstrated an increased number of mast cells in pregnant and
      intrapartum rats. Furthermore, mast cell degranulation was found to be prominent
      after antigestagen treatment. The degranulation was completely abolished by co
      treatment with the mast cell stabilizer. Biomechanical analysis showed that the
      mast cell stabilizer also inhibited the antigestagen induced cervical ripening to
      some extent. Thus, it is concluded that mast cell stabilizers might constitute a
      new approach in the treatment of preterm cervical ripening.

PMID- 9175698
TI  - Paramesonephric cyst of the uterosacral ligament.

PMID- 9175697
TI  - The mammalian oviduct: biochemistry and physiology.
AB  - Oviduct fluid and oviduct epithelium seem able to modulate in-time maturation and
      transport of gametes and embryos. They probably allow selection of spermatozoa
      through too early activation. Subtle changes in the composition of tubal
      secretion permit fertilization and embryo development in the best conditions. The
      mechanisms of these changes of oviduct fluid composition (induced by endocrine
      stimuli and/or by embryo) are under investigation. Numerous compounds isolated in
      oviduct fluid are now added to the synthetic media for in vitro maturation/in
      vitro fertilization/embryo culture (IVM/IVF/EC). The rationale is now to mimic
      more and more, the biochemical composition of tubal and uterine fluids even if
      interactions with embryo metabolism is still far from being understood.

PMID- 9175699
TI  - The transcriptional basis of chromosome pairing.
AB  - Pairing between homologous chromosomes is essential for successful meiosis;
      generally only paired homologs recombine and segregate correctly into haploid
      germ cells. Homologs also pair in some somatic cells (e.g. in diploid and
      polytene cells of Drosophila). How homologs find their partners is a mystery.
      First, I review some explanations of how they might do so; most involve base
      pairing (i.e. DNA-DNA) interactions. Then I discuss the remarkable fact that
      chromosomes only pair when they are transcriptionally active. Finally, I present
      a general model for pairing based upon the DNA-protein interactions involved in
      transcription. Each chromosome in the haploid set has a unique array of
      transcription units strung along its length. Therefore, each chromatin fibre will
      be folded into a unique array of loops associated with clusters of polymerases
      and transcription factors; only homologs share similar arrays. As these loops and
      clusters, or transcription factories, move continually, they make and break
      contact with others. Correct pairing would be nucleated when a promoter in a loop
      tethered to one factory binds to a homologous polymerizing site in another
      factory, before transcription stabilizes the association. This increases the
      chances that adjacent promoters will bind to their homologs, so that chromosomes
      eventually become zipped together with their partners. Pairing is then the
      inevitable consequence of transcription of partially-condensed chromosomes.

PMID- 9175700
TI  - Lateral mobility of plasma membrane lipids in bull spermatozoa: heterogeneity
      between surface domains and rigidification following cell death.
AB  - Compartmentalization of surface membrane antigens into discrete regions or
      domains is a characteristic feature of differentiated cells. In mammalian
      spermatozoa at least 5 surface domains are known, implying the presence of
      barriers or boundaries within the plasma membrane. Using the technique of
      fluorescence recovery after photobleaching (FRAP) to measure diffusibility of
      fluorescent lipid analogues 1,1'-dihexadecyl-3,3,3'3'-tetramethylindocarbocyanine
      (DiIC[16]) and 5-(N-octa-decanoyl) aminofluorescein (ODAF), we have investigated
      lipid topology and dynamics in the plasma membrane of ejaculated bull
      spermatozoa. Contrary to reports in the literature, we have found that DiIC(16)
      stains only dead or damaged spermatozoa whereas ODAF intercalates into the plasma
      membrane of both live and dead cells, each type showing a distinctive staining
      pattern. FRAP analysis with ODAF revealed that diffusion coefficients on live
      spermatozoa are significantly faster on the acrosome and postacrosome (29.3x10(
      9) cm2/second) than on the midpiece and principal piece (11.8x10(-9) cm2/second).
      Recovery (R) is >90% in all domains. ODAF diffusion also shows regionalized
      temperature-sensitivity with a 4-fold increase over the sperm head and a 1.8-fold
      increase on the tail between 20 degrees C and 37 degrees C. Remarkably, dead or
      permeabilized spermatozoa rapidly develop a large immobile phase (R<25%) over the
      whole plasma membrane. This rigidification is temperature insensitive and
      irreversible suggesting major changes in the physical state of membrane lipids.
      It is concluded that lipid diffusion in the plasma membrane of live bull
      spermatozoa is rapid and varies significantly between surface domains. Following
      permeabilization or cell death, however, a large immobile phase develops
      indicating substantial changes in membrane lipid disposition.

PMID- 9175701
TI  - AND-1, a natural chimeric DNA-binding protein, combines an HMG-box with
      regulatory WD-repeats.
AB  - Using a specific monoclonal antibody (mAb AND-1/23-5-14) we have identified, cDNA
      cloned and characterized a novel DNA-binding protein of the clawed toad, Xenopus
      laevis, that is accumulated in the nucleoplasm of oocytes and various other
      cells. This protein comprises 1,127 amino acids, with a total molecular mass of
      125 kDa and a pI of 5.27. It is encoded by a mRNA of approximately 4 kb and
      contains, in addition to clusters of acidic amino acids, two hallmark motifs: the
      amino-terminal part harbours seven consecutive 'WD-repeats', which are sequence
      motifs of about 40 amino acids that are characteristic of a large group of
      regulatory proteins involved in diverse cellular functions, while the carboxy
      terminal portion possesses a 63-amino-acid-long 'HMG-box', which is typical of a
      family of DNA-binding proteins involved in regulation of chromatin assembly,
      transcription and replication. The DNA-binding capability of the protein was
      demonstrated by DNA affinity chromatography and electrophoretic mobility shift
      assays using four-way junction DNA. Protein AND-1 (acidic nucleoplasmic DNA
      binding protein) appears as an oligomer, probably a homodimer, and has been
      localized throughout the entire interchromatinic space of the interphase
      nucleoplasm, whereas during mitosis it is transiently dispersed over the
      cytoplasm. We also identified a closely related, perhaps orthologous protein in
      mammals. The unique features of protein AND-1, which is a 'natural chimera'
      combining properties of the WD-repeat and the HMG-box families of proteins, are
      discussed in relation to its possible nuclear functions.

PMID- 9175702
TI  - The yeast VPS5/GRD2 gene encodes a sorting nexin-1-like protein required for
      localizing membrane proteins to the late Golgi.
AB  - Genetic analysis of late Golgi membrane protein localization in Saccharomyces
      cerevisiae has uncovered a large number of genes (called GRD) that are required
      for retention of A-ALP, a model late Golgi membrane protein. Here we describe one
      of the GRD genes, VPSS/GRD2, that encodes a hydrophilic protein similar to human
      sorting nexin-1, a protein involved in trafficking of the epidermal growth factor
      receptor. In yeast cells containing a vps5 null mutation the late Golgi membrane
      proteins A-ALP and Kex2p were rapidly mislocalized to the vacuolar membrane. A
      ALP was delivered to the vacuole in vps5 mutants in a manner independent of a
      block in the early endocytic pathway. vps5 null mutants also exhibited defects in
      both vacuolar morphology and in sorting of a soluble vacuolar protein,
      carboxypeptidase Y. The latter defect is apparently due to an inability to
      localize the carboxypeptidase Y sorting receptor, Vps10p, to the Golgi since it
      is rapidly degraded in the vacuole in vps5 mutants. Fractionation studies
      indicate that Vps5p is distributed between a free cytosolic pool and a
      particulate fraction containing Golgi, transport vesicles, and possibly
      endosomes, but lacking vacuolar membranes. Immunofluorescence microscopy
      experiments show that the membrane-associated pool of Vps5p localizes to an
      endosome-like organelle that accumulates in the class E vps27 mutant. These
      results support a model in which Vps5p is required for retrieval of membrane
      proteins from a prevacuolar/late endosomal compartment back to the late Golgi
      apparatus.

PMID- 9175703
TI  - A nematode gene required for sperm vesicle fusion.
AB  - During maturation of spermatids to motile spermatozoa in Caenorhabditis elegans,
      large vesicles called membranous organelles (MOs) fuse with the spermatid plasma
      membrane. Mutations in the gene fer-1 cause abnormal spermatozoa in which the MOs
      do not fuse, although they abut the plasma membrane normally. Here we describe
      the fer-1 gene, which we found to be approximately 8.6 kb in length and to encode
      a 6.2 kb transcript whose expression is limited to the primary spermatocytes, the
      cells in which the MOs form. fer-1 is predicted to encode a 235 kDa protein which
      is highly charged except for a putative transmembrane domain near the C terminus.
      We identified the mutations associated with five fer-1 alleles, all of which are
      missense mutations causing single amino acid changes. FER-1 is not similar to any
      characterized proteins in sequence databases, nor does it contain known
      functional motifs other than the predicted transmembrane domain. The C-terminal
      transmembrane domain makes FER-1 resemble some viral fusion proteins, suggesting
      it may play a direct role in MO-plasma membrane fusion. FER-1 does show
      significant sequence similarity to several predicted human proteins of unknown
      function. Two of the identified fer-1 mutations are located in regions of
      similarity between FER-1 and two of these predicted proteins. This strengthens
      the biological significance of these similarities and suggests these regions of
      similarity represent functionally important domains of FER-1 and the human
      proteins.

PMID- 9175704
TI  - Evidence of a non-conventional role for the urokinase tripartite complex
      (uPAR/uPA/PAI-1) in myogenic cell fusion.
AB  - Urokinase can form a tripartite complex binding urokinase receptor (uPAR) and
      plasminogen activator inhibitor type-1 (PAI-1), a component of the extracellular
      matrix (ECM). The components of the tripartite complex are modulated throughout
      the in vitro myogenic differentiation process. A series of experiments aimed at
      elucidating the role of the urokinase tripartite complex in the fusion of human
      myogenic cells were performed in vitro. Myogenic cell fusion was associated with
      increased cell-associated urokinase-type plasminogen activator (uPA) activity,
      cell-associated uPAR, and uPAR occupancy. Incubation of cultures with either uPA
      anticatalytic antibodies, or the amino-terminal fragment of uPA (ATF), which
      inhibits competitively uPA binding to its receptor, or anti-PAI-1 antibodies,
      which inhibit uPA binding to PAI-1, resulted in a 30 to 47% decrease in fusion.
      Incubation of cultures with the plasmin inhibitor aprotinin did not affect
      fusion. Decreased fusion rates induced by interfering with uPAR/uPA/PAI-1
      interactions were not associated with significant changes in mRNA levels of both
      the myogenic regulatory factor myogenin and its inhibitor of DNA binding, Id.
      Incubation of cultures with purified uPA resulted in a decrease in fusion, likely
      due to a competitive inhibition of PAI-1 binding of endogenous uPA. We conclude
      that muscle cell fusion largely depends on interactions between the members of
      the urokinase complex (uPAR/uPA/PAI-1), but does not require proteolytic
      activation of plasmin. Since the intrinsic muscle cell differentiation program
      appears poorly affected by the state of integrity of the urokinase complex, and
      since cell migration is a prerequisite for muscle cell fusion in vitro, it is
      likely that the urokinase system is instrumental in fusion through its connection
      with the cell migration process. Our results suggest that the urokinase
      tripartite complex may be involved in cell migration in a non conventional way,
      playing the role of an adhesion system bridging cell membrane to ECM.

PMID- 9175705
TI  - Binding of urokinase to plasminogen activator inhibitor type-1 mediates cell
      adhesion and spreading.
AB  - Urokinase plasminogen activator and its receptor are both found at the surface of
      the cell membrane in many cell types. The plasminogen activator inhibitor type-1
      (PAI-1) is often associated with the extracellular matrix. The spatial
      localization of these three molecules could account for their involvement in cell
      adhesion and/or migration. We have shown previously that the urokinase receptor
      mediates mechanical force transmission across the cell surface to the
      cytoskeleton. Here we investigated whether immobilized plasminogen activator
      inhibitor type 1 (PAI-1) could regulate cell spreading and cytoskeleton
      reorganization. Serum deprived human myogenic cells were plated in serum free
      medium onto bacteriologic dishes precoated with different extracellular matrix
      ligands (fibronectin, vitronectin, or type 1 collagen) or PAI-1 at increasing
      concentrations. The number of adherent cells and their projected area were
      quantitated after 3 hours of plating. PAI-1 promoted cell adhesion and spreading
      in a dose dependent manner. Addition of antibodies to PAI-1 inhibited the
      adhesion on PAI-1 coated dishes in a dose dependent way. The PAI-1 mediated cell
      adhesion required the presence of urokinase at the cell surface. Removal of the
      glycosylphosphatidylinositol (GPI)-linked proteins abolished cell adhesion on PAI
      1 dish, suggesting its dependence on the presence of the urokinase receptor, a
      GPI-linked receptor. Furthermore, addition of antibodies against alpha v beta3
      integrin completely inhibited cell adhesion on PAI-1, suggesting that alpha v
      beta3 might be the transmembrane molecule that physically connects the complex of
      PAI-1, urokinase, and urokinase receptor to the cytoskeleton. Visualization of
      spread cells stained for filamentous actin with confocal microscopy showed a dose
      dependent increase of filopodia on PAI-1 coated dishes and cytoskeletal
      reorganization, suggesting a migratory profile. These data indicate that PAI-1
      plays a direct role in dynamic cell adhesion particularly at the leading edge,
      where increased levels of urokinase plasminogen activator (uPA) and its receptor
      (uPAR) are localized in migrating cells. Immobilized PAI-1 could therefore serve
      to bridge the cell surface with the extracellular matrix via the formation of a
      multimolecular complex that includes alpha v beta3 integrins in myogenic cells.

PMID- 9175706
TI  - Keratin intermediate filament dynamics in cell heterokaryons reveals diverse
      behaviour of different keratins.
AB  - To study the dynamics of keratin intermediate filaments, we fused two different
      types of epithelial cells (PtK2 and BMGE+H) and studied how the keratins from the
      parental cells recombine and copolymerize to form the heterokaryon cytoskeleton.
      The behaviour of the keratins during this process was followed by
      immunofluorescence using specific antibodies. After fusion, the parental
      cytoskeletons undergo a depolymerization process most apparent in the region
      adjacent to the fusion area. The depolymerized subunits spread throughout the
      heterokaryon and copolymerize into a new hybrid cytoskeleton. The complete
      process is very rapid, occurring in 3-4 hours, thus demonstrating the highly
      dynamic nature of the keratin cytoskeleton. Although newly synthesised subunits
      contribute to the formation of the hybrid cytoskeleton, the process takes place
      with similar kinetics in the absence of protein synthesis, showing the dynamic
      nature of the keratins from pre-existing cytoskeletons. During this process,
      specific keratins behave differently. Keratins K8, K18, K5 and K10 are mobilised
      from the parental cytoskeletons and reassemble rapidly into the hybrid
      cytoskeleton (3-6 hours), whereas K14 requires a substantially longer period (9
      24 hours). Thus, different keratins, even when they form part of the same
      heterodimeric/tetrameric complexes, as is the case for K5 and K14, exhibit
      different dynamics. This suggests that individual polypeptides or homopolymeric
      complexes rather than exclusively heterodimeric/ tetrameric subunits, as is
      currently thought, can also take part in keratin intermediate filament assembly
      and dynamics. Biochemical analysis performed in the absence of protein synthesis
      revealed greater amounts of K5 than of K14 in the soluble pool of BMGE+H cells.
      Crosslinking and immunoprecipitation experiments indicated an excess of monomeric
      K5, as well as of K5/K14 heterodimers and K5 homodimers in the soluble pool.
      These results are in agreement with the different dynamic behaviour of these
      keratins observed in immunofluorescence. On the contrary, the phosphorylation
      levels of K5 and K14 are similar in both the soluble pool and the polymerized
      fraction, suggesting that phosphorylation does not play an important role in the
      different dynamics displayed by these two proteins. In summary, our results
      demonstrate that, following fusion, the keratin intermediate filament network
      reshapes rather rapidly and that keratins are highly dynamic proteins, although
      this mobility depends on each particular polypeptide.

PMID- 9175707
TI  - Occludin confers adhesiveness when expressed in fibroblasts.
AB  - Occludin is an integral membrane protein specifically associated with tight
      junctions. Previous studies suggest it is likely to function in forming the
      intercellular seal. In the present study, we expressed occludin under an
      inducible promotor in occludin-null fibroblasts to determine whether this protein
      confers intercellular adhesion. When human occludin is stably expressed in NRK
      and Rat-1 fibroblasts, which lack endogenous occludin and tight junctions but do
      have well developed ZO-1-containing adherens-like junctions, occludin colocalizes
      with ZO-1 to points of cell-cell contact. In contrast, L-cell fibroblasts which
      lack cadherin-based adherens junctions, target neither ZO-1 nor occludin to sites
      of cell contact. Occludin-induced adhesion was next quantified using a suspended
      cell assay. In NRK and Rat-1 cells, occludin expression induces adhesion in the
      absence of calcium, thus independent of cadherin-cadherin contacts. In contrast,
      L-cells are nonadhesive in this assay and show no increase in adhesion after
      induction of occludin expression. Binding of an antibody to the first of the
      putative extracellular loops of occludin confirmed that this sequence was exposed
      on the cell surface, and synthetic peptides containing the amino acid sequence of
      this loop inhibit adhesion induced by occludin expression. These results suggest
      that the extracellular surface of occludin is directly involved in cell-cell
      adhesion and the ability to confer adhesiveness correlates with the ability to
      colocalize with its cytoplasmic binding protein, ZO-1.

PMID- 9175708
TI  - Internalization of prolactin receptor and prolactin in transfected cells does not
      involve nuclear translocation.
AB  - Prolactin (PRL) interacts with a specific, well characterized plasma membrane
      receptor (PRLR) that is coupled to signal transduction pathways involving Jak2,
      Fyn, and MAP kinases, and signal transducers and activators of transcription
      (STAT). Although a few previous studies have indicated nuclear translocation of
      PRL in IL-2 stimulated T lymphocytes, PRL-dependent Nb2 lymphoma cell lines and
      235-1 lactotrophs, the mechanisms of nuclear targeting remain unknown and
      conflicting results have been reported concerning the putative nuclear
      translocation of the PRLR. We therefore decided to investigate nuclear
      translocation of PRLR and PRL in various cell lines transfected with an
      expression plasmid encoding PRLR, using confocal laser microscopy. We have
      constructed various cDNAs of the long and short forms of the rat PRLR containing
      an oligonucleotide encoding a Flag epitope inserted either just before the N
      terminal amino acid or in the C-terminal end of the mature receptor (named N
      terminal or C-terminal Flag-tagged PRLR). The corresponding receptors function as
      the PRLR in transfected cells: they are expressed at the plasma membrane and in
      compartments of the secretory pathway, they bind PRL with normal affinity (Kd=
      4x10(-10) M) and have the same capacity to stimulate the transcriptional activity
      of a milk protein (beta-casein) gene as wild-type PRLR. In addition, the tagged
      receptors are much more efficiently immunodetected using anti-Flag antibodies, as
      compared to anti-PRL antibodies (U5 or U6). Immunofluorescence combined with
      detailed confocal laser microscopy showed that addition of PRL (0 to 12 hours) to
      COS-7, CHO and NIH-3T3 transfected fibroblasts induces rapid internalization of
      the receptor (long form), without any translocation to the nucleus. Using PRL-R
      tagged both in the N-terminal or C-terminal regions of the mature receptor
      excludes the possibility of a cleaved fragment which could have been subsequently
      imported into the nucleus. An absence of nuclear translocation of PRLR was also
      observed in a 293 cell line stably expressing the receptor, and in physiological
      targets for PRL, i.e. in Nb2 lymphoma cells expressing the Nb2 form of the
      receptor or in BGME mammary gland epithelial cells upon overexpression of a Flag
      tagged PRLR. Similarly, the short form of the PRLR was not detected in nuclei of
      transfected COS cells upon PRL treatment. Clearly, our results provide evidence
      that internalization of the plasma membrane PRLR does not lead to nuclear
      translocation of the receptor, or part of it, in most fibroblasts and epithelial
      cells at physiological concentrations of PRL. Also, in co-localization
      experiments, PRL was internalized without nuclear translocation. Activation of
      STATs transcription factors and MAP kinases, as well as translocation of these
      proteins to the nucleus following their phosphorylation, probably remains the
      intracellular mechanism coupling stimulation to nuclear events.

PMID- 9175709
TI  - Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1,
      CD11b/CD18).
AB  - Myeloperoxidase is a leukocyte component able to generate potent microbicidal
      substances. A homologous invertebrate blood cell protein, peroxinectin, is not
      only a peroxidase but also a cell adhesion ligand. We demonstrate in this study
      that human myeloperoxidase also mediates cell adhesion. Both the human myeloid
      cell line HL-60, when differentiated by treatment with 12-O-tetradecanoyl-phorbol
      13-acetate (TPA) or retinoic acid, and human blood leukocytes, adhered to
      myeloperoxidase; however, undifferentiated HL-60 cells showed only minimal
      adhesion. No cells adhered to horseradish peroxidase, and cell adhesion to
      myeloperoxidase was not decreased by catalase, thus showing that peroxidase
      activity, per se, was neither sufficient nor necessary for the adhesion activity.
      Mannan, which has been reported to inhibit the binding of peroxidases to cells,
      did not affect adhesion to myeloperoxidase. However, adhesion to myeloperoxidase
      was inhibited by monoclonal antibodies to alpha M (CD11b) or to beta2 (CD18)
      integrin subunits, but not by antibodies to alpha L (CD11a), alpha M (CD11c), or
      to other integrins. Native myeloperoxidase mediated dose-dependent cell adhesion
      down to relatively low concentrations, and denaturation abolished the adhesion
      activity. It is evident that myeloperoxidase supports cell adhesion, a function
      which may be of considerable importance for leukocyte migration and infiltration
      in inflammatory reactions, that alpha M beta2 integrin (Mac-1 or CD11b/CD18)
      mediates this adhesion, and that the alphaM beta2 integrin-mediated adhesion to
      myeloperoxidase is distinct from the previously reported ability of this integrin
      to bind to certain denatured proteins at high concentrations.

PMID- 9175710
TI  - Modulation of 6-hydroxydopamine oxidation by various proteins.
AB  - The spontaneous autoxidation of the neurotoxin 6-hydroxydopamine proceeds by a
      free radical chain reaction involving the superoxide anion radical and produces
      the corresponding chromogen 6-hydroxydopamine quinone and hydrogen peroxide. The
      rate of this reaction is increased in the presence of ceruloplasmin and
      peroxidase, and reduced by superoxide dismutase, catalase, and DT-diaphorase. We
      report some explanations of why these proteins may increase or reduce the rate of
      autoxidation of 6-hydroxydopamine.

PMID- 9175711
TI  - Heme oxygenase induction with attenuation of experimentally induced corneal
      inflammation.
AB  - Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates
      cellular levels of heme and hemeproteins; certain of the latter, i.e. cytochrome
      P450s, generate pro-inflammatory products from endogenous substrates. Two HO
      isozymes, the products of distinct genes, have been described; HO-1 is the
      inducible one, whereas HO-2 is believed to be constitutively expressed. We
      studied the inducing effects of several metal compounds [CoCl2, SnCl2, ZnCl2,
      heme, and cobalt protoporphyrin (CoPP)] on HO-1 mRNA content and enzyme activity
      in cultures of rabbit corneal epithelial (RCE) cells; these metal compounds are
      known to induce HO in other tissues. Additionally, we studied HO-1 expression in
      an experimental model of ocular inflammation produced in rabbit corneas by
      extended contact lens wear, and the relation of HO expression to the induced
      inflammatory process. SnCl2 added to RCE cells in vitro produced marked time- and
      concentration-dependent increases in HO-1 mRNA and HO-1 enzyme activity; CoCl2,
      ZnCl2, and CoPP were inducers of HO as well, though to a lesser degree than
      SnCl2. Corneas treated for 6 days with contact lenses impregnated with SnCl2
      displayed substantially less corneal inflammation, swelling, and new vessel
      invasion than did controls; attenuation of ocular inflammation was paralleled by
      SnCl2-induced increases in HO mRNA and HO activity in corneal epithelial cells
      from treated eyes. It is suggested that amelioration of the inflammatory response
      produced by extended contact lens wear is due, in part, to the induction of high
      levels of HO-1 activity by SnCl2, which results in diminished production of pro
      inflammatory mediators generated through heme-dependent metabolic processes.
      Regulation of HO activity in this manner may have clinical applications.

PMID- 9175712
TI  - Inhibition of glucose-induced insulin secretion by the diacylglycerol lipase
      inhibitor RHC 80267 and the phospholipase A2 inhibitor ACA through stimulation of
      K+ permeability without diminution by exogenous arachidonic acid.
AB  - The effects of the diacylglycerol lipase inhibitor 1,6-bis
      (cyclohexyloximinocarbonyl-amino)-hexane (RHC 80267) and the phospholipase A2
      inhibitor N-(p-amylcinnamoyl)anthranilic acid (ACA) on insulin secretion and
      86Rb+ efflux in mouse pancreatic islets were studied. RHC 80267 (35 microM) and
      ACA (100 microM) inhibited glucose (16.7 mM)-induced insulin secretion, but did
      not inhibit insulin secretion induced by K+ (40 mM) or the phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (TPA; 0.16 microM). K+ (40 mM) or TPA (0.16
      microM) potentiated glucose (16.7 mM)-induced insulin secretion, and prevented
      inhibition of glucose (16.7 mM)-induced insulin secretion by RHC 80267 and ACA.
      In comparison, potentiation of glucose-induced insulin secretion by albumin-bound
      arachidonic acid (AA; 200 microM total; 10 microM free unbound) failed to
      counteract inhibition of glucose-induced insulin secretion by RHC 80267 or ACA,
      suggesting that inhibition of insulin secretion by these agents was not mediated
      by a decrease in AA accumulation in islets. Determination of 86Rb+ efflux, a
      marker of K+ channel activity, revealed that both RHC 80267 and ACA stimulated K+
      efflux from islets. These effects of RHC 80267 and ACA were observed at both 3.3
      and 16.7 mM glucose and persisted in Ca2+-free medium, suggesting that they may
      represent an opening of ATP-sensitive K+ channels. RHC 80267-mediated stimulation
      of 86Rb+ efflux was not mimicked by the diacylglycerol analog TPA (0.16 microM)
      and was not prevented by the diacylglycerol kinase inhibitor R 59022 (50 microM),
      suggesting that stimulation of 86Rb+ efflux did not reflect a conditional
      increase in diacylglycerol or in phosphatidic acid upon inhibition of
      diacylglycerol lipase. In contrast, TPA (0.16 microM) attenuated RHC 80267 and
      ACA stimulation of 86Rb+ efflux. Addition of AA (200 microM total; 10 microM free
      unbound) stimulated 86Rb+ efflux, suggesting that stimulation of 86Rb+ efflux by
      RHC 80267 and ACA was not due to a decrease in AA accumulation. This stimulation
      by AA was not dependent on AA metabolism because it persisted in the presence of
      the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 50 microM) or the
      cyclooxygenase inhibitor indomethacin (50 microM). In contrast to RHC 80267 and
      ACA, AA stimulation of 86Rb+ efflux was attenuated in Ca2+-free medium, probably
      implicating Ca2+-sensitive K+ channels in AA regulation of 86Rb+ efflux. Parallel
      experiments with diazoxide (100 microM) revealed that RHC 80267 and ACA mimicked
      the effects of diazoxide, a specific activator of ATP-sensitive K+ channels in
      islets, on both insulin secretion and 86Rb+ efflux. In conclusion, it is
      suggested that RHC 80267 and ACA, independently of their action on AA release,
      may inhibit glucose-induced insulin secretion by the opening of ATP-sensitive K+
      channels in islets.

PMID- 9175713
TI  - Metabolism of the vitamin D analog EB 1089: identification of in vivo and in
      vitro liver metabolites and their biological activities.
AB  - 1(S),3(R)-dihydroxy-20(R)-(5'-ethyl-5'-hydroxy-hepta-1'(E),3'(E)-dien -1'-yl)
      9,10-secopregna-5(Z),7(E),10(19)-triene (EB 1089) is a novel analog of the
      vitamin D hormone, calcitriol that has been modified in the side-chain resulting
      in an increased metabolic stability relative to other side-chain modified analogs
      (e.g. calcipotriol and 22-oxacalcitriol). To further investigate the metabolism
      of EB 1089, we set out to study this metabolism both in the rat in vivo as well
      as in the postmitochondrial liver fractions from rat, man, and minipig in vitro.
      The same pattern of metabolism was observed in all biological systems employed,
      both in vivo and in vitro, namely 26- and 26a-hydroxylation of EB 1089. The same
      metabolites were produced using cultured cell systems (Shankar et al., see this
      issue). All the possible isomers of 26- and 26a-hydroxy EB 1089 were synthesised
      and these were compared to biologically generated material using HPLC, NMR, and
      GC-MS techniques. The predominant natural isomer observed in vitro and in vivo in
      rats as well as in vitro in humans was identified to be (25S),26R-hydroxy EB
      1089. The biological activities of the EB 1089 metabolites on cell growth
      regulation were 10- to 100-fold lower than that of EB 1089. The effects of the
      metabolites on calcium metabolism in vivo were comparable to the effect of EB
      1089; however, these effects were reduced for the major metabolite in rat and man
      and for the isomers of 26a-hydroxy EB 1089. We conclude that EB 1089 is
      metabolised by a different route of side-chain metabolism than calcitriol and
      that this may explain its relative metabolic stability in pharmacokinetic
      experiments in vivo compared to that of other vitamin D analogs.

PMID- 9175714
TI  - Involvement of growth hormone as a regulating factor in sex differences of mouse
      hepatic aldehyde oxidase.
AB  - The participation of circulating growth hormone (GH) as a regulator of sex
      differences in hepatic aldehyde oxidase (AO) activity in ddy mice was examined.
      The 2- to 3-fold higher activities in adult male mice compared with adult female
      mice were decreased to the female levels by neonatal pretreatment with monosodium
      glutamate (MSG) or monosodium aspartate (MSA), either of which is known to reduce
      circulating GH levels. A decline of the activities in the MSG-treated male mice
      was restored nearly to the male control levels by subsequent injections of human
      GH every 12 hr for 7 days. These changes in AO activities in male mice caused by
      the excitotoxic amino acids were not observed in females. Hypophysectomy markedly
      decreased hepatic AO activities in male mice and partially in female mice. The
      activities in hypophysectomized male mice were restored again to levels similar
      to the control males by intermittent injections of human GH. Administration of
      testosterone propionate (TP) significantly increased the activities of hepatic AO
      in intact female mice, but not in MSA-treated or hypophysectomized females. On
      the other hand, the AO activities in adult male mice were decreased partially by
      the administration of estradiol benzoate. These results indicate that the
      pituitary GH is involved as one of the major regulatory factors of sex
      differences in the activities of hepatic AO in mice and TP also contributes to
      maintaining the higher activity in male mice mainly through the hypothalamus
      pituitary system.

PMID- 9175715
TI  - Inhibition of M3 muscarinic acetylcholine receptor-mediated Ca2+ influx and
      intracellular Ca2+ mobilization in neuroblastoma cells by the Ca2+/calmodulin
      dependent protein kinase inhibitor 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L
      trosyl]-4-phenylpiperazin e (KN-62).
AB  - The role of Ca2+/calmodulin-dependent protein kinase (CaM kinase; EC 2.7.1.123)
      in the generation of Ca2+ signals by muscarinic acetylcholine receptors (mAChR)
      was studied. Changes in intracellular Ca2+ concentrations ([Ca2+]i) induced by
      mAChR activation were monitored in SK-N-SH human neuroblastoma cells using the
      dye Fura-2. SK-N-SH cells express M3 mAChR, as well as CaM kinase types II and
      IV, which are specifically inhibited by the CaM kinase antagonist KN-62 (1-[N,O
      bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne).
      Carbamylcholine (100 microM) elicited an initial transient peak in [Ca2+]i due to
      mobilization of Ca2+ from internal stores, followed by a sustained elevation in
      [Ca2+]i that depended on the influx of extracellular Ca2+ and which was inhibited
      by EGTA and Ni2+. These mAChR-induced Ca2+ signals were diminished to an equal
      extent by preincubating the cells with 0.01 to 100 microM KN-62. KN-62 inhibited
      mAChR-induced Ca2+ influx and mobilization from internal stores by about 25-30%,
      producing a half-maximal effect at approximately 1 microM. In contrast, KN-62 (25
      microM) almost completely abolished carbamylcholine-stimulated entry of divalent
      cations through Mn2+-permeant channels, as revealed by Mn2+ quenching of Fura-2
      fluorescence. KN-62 also almost completely abolished Ca2+ influx induced by
      depolarization of the cells with 25 mM K+ (IC50 = 3 microM). These results
      suggest that CaM kinases regulate both the mobilization of intracellular Ca2+ and
      the stimulation of Ca2+ influx that are induced by mAChR activation, and indicate
      that the mAChR-induced influx of Ca2+ occurs through Ca2+ channels other than, or
      in addition to, the voltage-gated calcium channels or Mn2+-permeant channels
      which are inhibited by KN-62.

PMID- 9175716
TI  - Comet assay studies on the activation of two diaziridinylbenzoquinones in K562
      cells.
AB  - Two versions of the comet assay have been used to identify the difference in the
      modes of action of AZQ (2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4
      benzoquinone) and BZQ (2,5-diaziridinyl-3,6-bis(ethanolamino)-1,4-benzoquinone)
      in human leukaemia K562 cells and a K562-derived resistant cell line, BZQR. Using
      the standard alkaline assay, AZQ produced dose-dependent changes in the mean
      comet moments from K562 cells, consistent with the formation of strand breaks.
      This damage was repaired over a period of 6 hr after removal of the drug. The
      resistant cell line, BZQR, showed much smaller changes in comet moment under
      identical conditions. In contrast to AZQ, BZQ did not produce any measurable
      strand breaks in the K562 or BZQR cells. However, the comet
      radiation/crosslinking assay and a fluorescence-based assay revealed that BZQ
      extensively cross-links DNA in K562 cells. The extent of cross-linking is greatly
      reduced in the resistant cell line.

PMID- 9175717
TI  - Effects of synthetic oligonucleotides on human complement and coagulation.
AB  - Oligodeoxynucleotide phosphorothioates (PS-oligos) are being studied as novel
      therapeutic agents based on their ability to inhibit gene expression. Preclinical
      studies produced unanticipated complement and coagulation effects in monkeys
      receiving high-dose PS-oligo. In the present in vitro studies, PS-oligo inhibited
      normal human blood clotting as well as subsequent assays for prothrombin fragment
      PF(1+2) and hemolytic complement. PS-oligo treatment of normal donor plasma
      produced concentration-dependent prolongations of clotting times, with the
      activated partial thromboplastin time more sensitive than prothrombin time or
      thrombin clotting time. PS-oligo treatment of normal donor serum similarly
      reduced hemolytic complement activity in a concentration-dependent manner.
      Reduced hemolysis correlated with increased levels of complement fragment C4d.
      The anti-heparin drug protamine sulfate inhibited in vitro effects of PS-oligo in
      both complement and coagulation assays, suggesting that charged residues in
      internucleotide linkages of PS-oligo mediated the observed activities. Therefore,
      oligonucleotides with varying internucleotide linkages, nucleotide sequence, or
      secondary structure were compared. Both complement and coagulation effects
      appeared to be independent of nucleotide sequence but were strongly related to
      the nature of internucleotide linkages. Several of these modified
      oligonucleotides have been shown previously to retain potent antisense activity
      and thus may represent viable alternatives for antisense therapeutics.

PMID- 9175718
TI  - Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous
      aldehydes.
AB  - 4-Hydroxynonenal, a product of oxidative degradation of unsaturated lipids, is an
      endogenous reactive alpha,beta-unsaturated aldehyde with numerous biological
      activities. 4-Hydroxynonenal rapidly inactivated glutathione reductase in an
      NADPH-dependent reaction. Inactivation appears to involve the initial formation
      of an enzyme-inactivator complex, K(D) = 0.5 microM, followed by the inactivation
      reaction, k = 1.3 x 10(-2) min(-1). alpha,beta-Unsaturated aldehydes such as
      acrolein, crotonaldehyde, and cinnamaldehyde also inactivated glutathione
      reductase, although rates varied widely. Inactivation of glutathione reductase by
      alpha,beta-unsaturated aldehydes was followed by slower NADPH-independent
      reactions that led to formation of nonfluorescent cross-linked products,
      accompanied by loss of lysine and histidine residues. Other reactive endogenous
      aldehydes such as methylglyoxal, 3-deoxyglucosone, and xylosone inactivated
      glutathione reductase by an NADPH-independent mechanism, with methylglyoxal being
      the most reactive. However, 2-oxoaldehydes were much less effective than 4
      hydroxynonenal. Inactivation of glutathione reductase by these 2-oxoaldehydes was
      followed by slower reactions that led to the formation of fluorescent cross
      linked products over a period of several weeks. These changes were accompanied by
      loss of arginine residues. Thus, the sequence of events is different for
      inactivation and modification of glutathione reductase by alpha,beta-unsaturated
      aldehydes compared with 2-oxoaldehydes with respect to kinetics, NADPH
      requirements, fluorescence changes, and loss of amino acid residues. The ability
      of 4-hydroxynonenal at low concentrations to inactivate glutathione reductase, a
      central antioxidant enzyme, suggests that oxidative degradation of unsaturated
      lipids may initiate a positive feedback loop that enhances the potential for
      oxidative damage.

PMID- 9175719
TI  - Dissociation between phosphodiesterase inhibition and antiproliferative effects
      of phosphodiesterase inhibitors on the Dami cell line.
AB  - Phosphodiesterase (PDE) inhibitors were shown to inhibit proliferation of various
      cell types. The present investigation was designed to study the activity of
      selective PDE inhibitors (8-MeoMIX, milrinone, trequinsin, rolipram, RO-201724,
      zaprinast, and MY-5445) on the proliferation of the Dami cell line in relation to
      their effects on cAMP levels and PDE isoenzymes isolated from Dami cells. All
      compounds, except 8-MeoMIX, elicited antiproliferative effects. Trequinsin, RO
      201724, and MY-5445 (100 microM) were found to inhibit cell growth up to 60%,
      83%, and 85%, respectively; milrinone, rolipram and zaprinast elicited only weak
      effects (19-21% at 100 microM). Their growth-inhibitory effects could not be
      related to their effects on cAMP levels. In addition, although PDE type III and
      IV inhibitors potentiated cAMP formation due to adenylycyclase activation, no
      potentiation could be observed when considering their antiproliferative effect.
      Separation and characterization of PDE of Dami cells revealed the existence of
      types III, IV, and V isoenzymes. The PDE inhibition found for the PDE inhibitors
      could not explain their antiproliferative effects. The lack of correlation with
      cAMP concentrations or PDE inhibition and the high concentrations needed to
      elicit antiproliferative effects suggest the implication of other parameters,
      such as cytotoxicity or lipophilicity, or other targets in addition to PDE for
      the PDE inhibitors tested. Lipophilicity did not seem to be of importance in
      antiproliferative effects. In contrast, cytotoxic effects, in particular those of
      trequinsin and MY-5445, could partially explain their negative action on cell
      growth.

PMID- 9175720
TI  - Transforming growth factor-beta3 protection of epithelial cells from cycle
      selective chemotherapy in vitro.
AB  - The transforming growth factor-beta (TGF-beta) family of regulatory growth
      factors can reversibly arrest cell division in the G1 phase of the cell cycle.
      Previously, TGF-beta3 was shown to protect epithelial cells and hematopoietic
      cells from cytotoxic damage in vitro and in vivo, and to reduce the severity and
      duration of oral mucositis induced by 5-fluorouracil (5-FU) in vivo. In the
      present study, we tested whether TGF-beta3 can protect epithelial cells from a
      range of chemotherapy drugs with differing mechanisms of action, using the CCL64
      cell line as a model system. We report that preincubation of cells with TGF-beta3
      for 24 hr resulted in enhanced clonogenicity following exposure to vinblastine,
      vincristine, etoposide, taxol, ara-C, methotrexate, or 5-FU. Protection was
      measured in colony-forming assays, which demonstrated that the protected cells
      could re-enter the cell cycle and undergo multiple rounds of cell division. At
      high cytotoxic drug concentrations, absolute colony counts were increased for the
      cultures prearrested by TGF-beta3, as compared with the proliferating control
      cultures. The effects of TGF-beta3 were reduced for cisplatin and doxorubicin,
      drugs that are toxic to cells throughout the cell cycle. Thus, TGF-beta3 can
      effectively reduce the cytotoxicity of anticancer drugs that act predominantly in
      S or M phase of the cell cycle.

PMID- 9175721
TI  - Transcriptional activation of the human estrogen receptor by DDT isomers and
      metabolites in yeast and MCF-7 cells.
AB  - In this study, we determined whether the DDT isomers p,p'-DDT [1,1,1,-trichloro
      2,2-bis(p-chlorophenyl)ethane], o,p'-DDT [1,1,1-trichloro-2(p-chlorophenyl)-2-(o
      chlorophenyl)ethane], and their metabolites p,p'-DDD [1,1-dichloro-2,2-bis(p
      chlorophenyl)ethane], o,p'-DDD [1,1-dichloro-2-(p-chlorophenyl)-2-(o
      chlorophenyl)ethane], p,p'-DDE [1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene],
      o,p'-DDE [1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethylene], and p,p'
      DDA [2,2-bis(p-chlorophenyl)acetic acid], could bind to and transcriptionally
      activate the human estrogen receptor (hER). Novel results from competitive
      binding assays showed that o,p'-DDD, o,p'-DDE, and p,p'-DDT, as well as the
      established environmental estrogen o,p'-DDT, were able to bind specifically to
      the hER with approximately 1000-fold weaker affinities for the hER than that of
      estradiol. In contrast, only o,p'-DDT, but not p,p'-DDT, bound to the rat
      estrogen receptor. Moreover, two yeast expression-reporter systems, constructed
      to test if the DDT isomers and metabolites could transcriptionally activate the
      hER, demonstrated that an o,p'-DDT metabolite could transactivate the hER or LexA
      hER fusion protein with just a 140- to 300-fold weaker potency than that of
      estradiol. The DDT isomers and metabolites that bound the hER in vitro triggered
      estrogen receptor-mediated transcription of the lacZ reporter gene in the yeast
      systems. Furthermore, the DDT isomers and metabolites that transactivated the hER
      elicited an additive response when given together or with estradiol. The DDT
      isomers and metabolites that triggered transcription of the yeast expression
      reporter systems also stimulated two estrogenic endpoints in estrogen-responsive
      MCF-7 cells: the induction of the progesterone receptor and the down-regulation
      of the hER. Thus, in MCF-7 cells and in yeast expression-reporter systems,
      certain DDT isomers and metabolites act directly as agonists and transactivate
      the hER at concentrations found in human tissues.

PMID- 9175722
TI  - Impairment of phosphatidylinositol signaling in acetylshikonin-treated
      neutrophils.
AB  - In rat neutrophils, formylmethionyl-leucyl-phenylalanine (fMLP)-induced inositol
      phosphate formation was concentration-dependently inhibited by acetylshikonin as
      well as by a putative phospholipase C (PLC) inhibitor [6-[[17beta-3-methoxyestra
      1,3,5(10)-trien-17-yl]amino]hexyl]-1H-p yrrole-2,5-dione (U73122). The IC50 value
      of acetylshikonin for the inhibition of inositol trisphosphate (IP3) formation
      was estimated to be 16.1 +/- 1.5 microM. The reduction of inositol phosphate
      levels appeared to reflect inhibition of PLC activity because the hydrolysis of
      phosphatidylinositol 4,5-bisphosphate (PIP2) catalyzed by a soluble fraction from
      neutrophils was also inhibited by acetylshikonin (IC50 value 21.4 +/- 6.1 microM)
      over the same range of concentrations. Although acetylshikonin alone evoked Ca2+
      and Mn2+ influx into neutrophils in Ca2+-containing medium, acetylshikonin, like
      U73122, inhibited Ca2+ release (IC50 value approximately 5.3 +/- 0.4 microM) from
      internal stores in Ca2+-free medium. These results indicate that acetylshikonin
      inhibits phosphatidylinositol signaling in neutrophils.

PMID- 9175724
TI  - Hepatic and intestinal metabolism of indinavir, an HIV protease inhibitor, in rat
      and human microsomes. Major role of CYP3A.
AB  - The metabolism of indinavir, a human immune deficiency virus (HIV) protease
      inhibitor, has been characterized extensively in rats and humans. All oxidative
      metabolites found in vivo were formed when indinavir was incubated with NADPH
      fortified hepatic and intestinal microsomes obtained from rats and humans. In
      vitro kinetic studies revealed that Vmax/Km values (microL/min/mg protein) in rat
      and human liver microsomes were approximately 8- and 2-fold greater than those in
      the intestinal microsomes of the corresponding species (55.8 and 6.7 for the
      liver and intestine, respectively, in rats; 16.5 and 7.7 for the liver and
      intestine, respectively, in humans). However, when Vmax/Km was scaled up to
      intrinsic clearance (mL/min/kg body weight), hepatic intrinsic clearance was much
      greater than the intestinal clearance by 50- to 200-fold. These results suggest
      that the liver plays a much greater role in first-pass metabolism of indinavir
      than the intestine in both species. Consistently, ketoconazole, a selective
      inhibitor for CYP3A, and an anti-rat CYP3A1 antibody strongly inhibited hepatic
      and intestinal metabolism of indinavir in both rats and humans, suggesting the
      involvement of CYP3A isoforms in both organs. Oral treatment of rats with
      dexamethasone (50 mg/kg/day for 4 days), a potent CYP3A inducer, increased both
      hepatic and intestinal metabolism of indinavir by a factor of 7 and 3,
      respectively. Furthermore, indinavir selectively inhibited 6beta-hydroxylase
      activity of testosterone, a CYP3A marker activity, in rat and human liver
      microsomes; the interactions between testosterone and indinavir were competitive
      with Ki values of < 1.0 microM.

PMID- 9175723
TI  - Alteration by flutamide of neutrophil response to stimulation. Implications for
      tissue injury.
AB  - When activated, inflammatory cells such as polymorphonuclear leukocytes (PMNs)
      can damage isolated hepatocytes in vitro. These studies were performed to
      determine if flutamide activates PMNs. Flutamide (Eulexin) is an orally active,
      nonsteroidal antiandrogen that can cause liver injury associated with
      inflammation. Activation of PMNs was assessed from the production of superoxide
      anion and the release of myeloperoxidase in the presence or absence of flutamide
      and phorbol myristate acetate (PMA) or f-methionyl-leucyl-phenylalanine (fmlp).
      In addition, hepatocytes were cocultured with PMNs stimulated with PMA or fmlp in
      the presence or absence of flutamide, and cytotoxicity to hepatocytes was
      evaluated from the release of alanine aminotransferase into the medium. Flutamide
      alone did not stimulate the generation of superoxide anion by PMNs but
      potentiated its production in response to PMA. At lower concentrations of
      flutamide (i.e. 25 microM), there was a tendency toward increased release of
      myeloperoxidase, whereas at higher concentrations (i.e. 75-100 microM) flutamide
      inhibited degranulation in response to fmlp. In coculture with hepatocytes, PMNs
      exposed to either flutamide, fmlp, or PMA alone caused a significant increase in
      release of alanine aminotransferase. Hepatocellular toxicity caused by PMNs
      incubated with flutamide and PMA was additive and was not affected by the
      addition of superoxide dismutase and catalase. Flutamide had no significant
      effect on fmlp-induced injury in cocultures. These data indicate that flutamide
      alters the activation of PMNs by subsequent stimuli in vitro. In addition, in the
      presence of flutamide, minor PMN-mediated injury to isolated hepatocytes was
      observed.

PMID- 9175725
TI  - Impact of schedule on leucovorin potentiation of fluorouracil antitumor activity
      in dietary folic acid deplete mice.
AB  - A dietary folic acid depleted mouse model was established and used to evaluate
      the relationship between elevation of reduced folates after leucovorin (LV)
      administration and potentiation of fluorouracil (FU) response of an implanted
      tumor. C3H mouse mammary adenocarcinomas from mice maintained on a folic acid
      deplete diet had modestly decreased methylenetetrahydrofolate and
      tetrahydrofolate levels, and were somewhat less responsive to FU alone compared
      with replete animals. LV administration resulted in a substantial increase in
      tumor folate by 1 hr that returned to near basal levels by 12 hr. Reduced folates
      were elevated to a lesser extent in animals on a standard diet. Tumor growth was
      suppressed approximately 80% when FU was administered to depleted animals 1 hr
      after LV administration, compared with approximately 50% suppression in control
      mice. LV administered 12 hr before FU resulted in tumor growth stimulation that
      was consistent with the pronounced growth stimulation when LV was administered
      without FU. These results show that dietary folic acid depletion can lead to a
      more responsive FU/LV model and that administration of LV at an improper time
      before FU not only can fail to potentiate but also can result in tumor growth
      stimulation.

PMID- 9175726
TI  - Modulation of cytotoxicity of chemotherapeutic drugs by activated H-ras.
AB  - Cells from a single MCF-7 clone were transfected with an isopropyl-1-thio-beta-D
      galactopyranoside (IPTG)-inducible construct containing activated human H-ras
      with a Gly12 --> Val12 mutation. Expression of H-ras was induced by the presence
      of IPTG with low background. MCF-7-ras clones were examined for sensitivity to a
      wide variety of drugs under both induced and non-induced conditions. When
      expression of the activated ras was induced, these clones showed markedly
      increased resistance to cisplatin and mitomycin C, moderately increased
      resistance to methotrexate and trimetrexate, and no increased resistance to other
      drugs including taxol, doxorubicin, and etoposide. A DNA fragmentation assay
      revealed that DNA in MCF-7-ras cells treated with cisplatin under induced
      conditions was intact, whereas extensive degradation of DNA occurred in similarly
      treated cells under non-induced conditions. This result, along with the fact that
      MCF-7-ras cells, upon induction of the activated H-ras, showed increased
      resistance to drugs that bind DNA, indicates that the activated H-ras may play a
      role in the DNA repair process.

PMID- 9175727
TI  - 3-Morpholinosydnonimine as instigator of a glibenclamide-sensitive reduction in
      the insulin secretory rate.
AB  - The nitric oxide (NO) donor SIN-1 (3-morpholinosydnonimine) induced a
      concentration-dependent inhibition of the secretory response to glucose. The
      negative insulinotropic action of SIN-1 was attenuated by the hypoglycemic
      sulfonylurea glibenclamide. Moreover, the NO donor enhanced 86Rb outflow from
      perfused islets and reduced the glucose-induced increase in 45Ca outflow. The
      present data provide further evidence that NO donors impair the secretory
      response to glucose, at least in part, by activating the ATP-sensitive K+
      channels.

PMID- 9175728
TI  - Dystroglycan is essential for early embryonic development: disruption of
      Reichert's membrane in Dag1-null mice.
AB  - Dystroglycan is a central component of the dystrophin-glycoprotein complex (DGC),
      a protein assembly that plays a critical role in a variety of muscular
      dystrophies. In order to better understand the function of dystroglycan in
      development and disease, we have generated a null allele of dystroglycan
      (Dag1neo2) in mice. Heterozygous Dag1neo2 mice are viable and fertile. In
      contrast, homozygous Dag1neo2 embryos exhibit gross developmental abnormalities
      beginning around 6.5 days of gestation. Analysis of the mutant phenotype
      indicates that an early defect in the development of homozygous Dag1neo2 embryos
      is a disruption of Reichert's membrane, an extra-embryonic basement membrane.
      Consistent with the functional defects observed in Reichert's membrane,
      dystroglycan protein is localized in apposition to this structure in normal egg
      cylinder stage embryos. We also show that the localization of two critical
      structural elements of Reichert's membrane--laminin and collagen IV--are
      specifically disrupted in the homozygous Dag1neo2 embryos. Taken together, the
      data indicate that dystroglycan is required for the development of Reichert's
      membrane. Furthermore, these results suggest that disruption of basement membrane
      organization might be a common feature of muscular dystrophies linked to the DGC.

PMID- 9175729
TI  - Evolution of the human RH (rhesus) blood group genes: a 50 year old prediction
      (partially) fulfilled.
AB  - Almost exactly 50 years ago, R. A. Fisher and R. Race proposed a model for the
      evolution of the RH (rhesus) genes in which the less common haplotypes were
      derived from the commoner ones by recombination, and in which the gene order was
      D-C-E. No direct-evidence bearing on this model was available then, and has not
      been until now. Here we present evidence for non-reciprocal intergenic exchange
      (gene conversion) occurring once in human history to generate the common RHCE
      allele, Ce. We have also used new polymorphisms to construct haplotypes which
      suggest that intragenic recombination played a major role in the generation of
      the less common haplotypes, but only if RHD lies 3' of RHCE, i.e. the order is C
      E-D. We provide both genetic and physical evidence supporting this arrangement.

PMID- 9175730
TI  - Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is
      not transmitted through the female germline.
AB  - Choroideremia (CHM) is an X-linked progressive eye disorder which results from
      defects in the human Rab escort protein-1 (REP-1) gene. A gene targeting approach
      was used to disrupt the mouse chm/rep-1 gene. Chimeric males transmitted the
      mutated gene to their carrier daughters but, surprisingly, these heterozygous
      females had neither affected male nor carrier female offspring. The targeted rep
      1 allele was detectable, however, in male as well as female blastocyst stage
      embryos isolated from a heterozygous mother. Thus, disruption of the rep-1 gene
      gives rise to lethality in male embryos; in female embryos it is only lethal if
      the mutation is of maternal origin. This observation can be explained by
      preferential inactivation of the paternal X chromosome in murine extraembryonic
      membranes suggesting that expression of the rep-1 gene is essential in these
      tissues. In both heterozygous females and chimeras the rep-1 mutation causes
      photoreceptor cell degeneration. Consequently, conditional rescue of the
      embryonic lethal phenotype of the rep-1 mutation may provide a faithful mouse
      model for choroideremia.

PMID- 9175731
TI  - The human Achaete-Scute homologue 2 (ASCL2,HASH2) maps to chromosome 11p15.5,
      close to IGF2 and is expressed in extravillus trophoblasts.
AB  - Here we describe the cloning of the human Achaete Scute Homologue 2 (HASH2) gene,
      officially designated ASCL2 (Achaete Scute complex like 2), a homologue of the
      Drosophila Achaete and Scute genes. In mouse, this gene is imprinted and maps to
      chromosome 7. We mapped the human homologue close to IGF2 and H19 at 11p15.5, the
      human region syntenic with mouse chromosome 7, indicating that this imprinted
      region is highly conserved in mouse and man. HASH2 is expressed in the
      extravillus trophoblasts of the developing placenta only. The lack of HASH2
      expression in non-malignant hydatidiform (androgenetic) moles indicates that
      HASH2 is also imprinted in man.

PMID- 9175732
TI  - Leptin receptor gene variation and obesity: lack of association in a white
      British male population.
AB  - Leptin, a hormone secreted by adipocytes, plays a pivotal role in the control of
      body weight. Rodents with mutations in the leptin receptor gene develop morbid
      obesity. It is possible, therefore, that leptin receptor gene mutations
      contribute to human obesity. To test this possibility, we determined the entire
      coding sequence of the human leptin receptor cDNA from peripheral blood
      lymphocytes of 22 morbidly obese patients with body-mass index (BMI) between 35.1
      and 60.9 kg/m2. We identified five common DNA sequence variants distributed
      throughout the coding sequence at codons 109, 223, 343, 656 and 1019, one rare
      silent mutation at codon 986 and one novel alternatively spliced form of
      transcript. None of the five common variants, including the three that predict
      amino acid changes, are null mutations causing morbid obesity, because
      homozygotes for the variant sequences were also found in lean subjects.
      Furthermore, the frequency of each variant allele and the distribution of
      genotypes and haplotypes were similar in 190 obese (BMI >28 kg/m2) and 132 lean
      (BMI <22 kg/m2) white British males selected from a population-based
      epidemiological survey. In these subjects, there was no evidence for a
      significant effect of the common variants on obesity or obesity-related
      phenotypes. These results suggest that mutations in the leptin receptor gene are
      not a common cause of human obesity.

PMID- 9175733
TI  - Somatic instability of the myotonic dystrophy (CTG)n repeat during human fetal
      development.
AB  - Myotonic dystrophy is characterised by the striking level of somatic
      heterogeneity seen between and within tissues of the same patient, which probably
      accounts for a significant proportion of the pleiotropy associated with this
      disorder. The congenital form of the disease is associated with the largest
      (CTG)n repeat expansions. We have investigated the timing of instability of
      myotonic dystrophy (CTG)n repeats in a series of congenitally affected fetuses
      and neonates. We find that during the first trimester the repeat is apparently
      stable and that instability only becomes detectable during the second and third
      trimesters. In our series repeat instability is apparent only after 13 weeks
      gestational age and before 16 weeks. The appearance of heterogeneity shows some
      tissue specificity, with heart most commonly having the largest expansion. The
      degree of heterogeneity is not correlated with initial expansion size as gauged
      by chorionic villus and blood (CTG)n repeat sizes.

PMID- 9175734
TI  - A novel mechanism generating short deletion/insertions following slippage is
      suggested by a mutation in the human alpha2-globin gene.
AB  - A novel mechanism generating short deletion/insertions is described based on a
      mutation in the human alpha2-globin gene. A deletion of 9 bp (codons 39-41) is
      replaced by an eight nucleotide insertion, duplicating the adjacent downstream
      sequence. We propose that the mutation arose by slipped strand mispairing (SSM),
      creating a single-stranded loop, followed by DNA elongation, strand breathing and
      the formation of a mismatch bubble. An extensive literature search has revealed
      six additional deletion/insertion mutations in humans in which the inserted
      nucleotides come from the same DNA strand. Our model explains all six mutations,
      suggesting that rearrangement of a mismatch loop or bubble during DNA replication
      may be not uncommon.

PMID- 9175735
TI  - Expression of mutated glucocerebrosidase alleles in human cells.
AB  - Gaucher disease is a heterogeneous disease characterized by impaired activity of
      the lysosomal enzyme glucocerebrosidase. This heterogeneity is attributed to a
      large number of mutations in the corresponding gene. In order to test the
      biochemical properties of some mutations prevalent among Israeli populations, the
      normal human glucocerebrosidase cDNA and cDNAs carrying mutations N370S, L444P,
      D409H, recTL, recNcil, P415R and 84GG were coupled to the T7 RNA polymerase
      promoter in a vaccinia virus-derived expression vector (pTM-1). Recombinant
      viruses were produced and used to infect human tissue culture cells. RNA and
      protein stability, recognition by anti-glucocerebrosidase monoclonal antibodies
      and intracellular enzymatic activity were measured. The results demonstrated that
      the D409H allele directed synthesis of cytoplasmic RNA with decreased stability
      compared with its normal counterpart or other mutated forms. The D409H and L444P
      mutated proteins had lower stability than that of their normal counterpart, while
      the recNcil-mutated protein was more stable. Only glucocerebrosidase forms
      harboring leucine at position 444 were recognized by the anti-glucocerebrosidase
      monoclonal antibodies used (8E4 and 2C7). Measurements of enzymatic activity of
      the recombinant proteins in cells loaded with a fluorescent glucosylceramide
      demonstrated that the N370S mutated enzyme had activity similar to that of the
      normal enzyme. The other mutated enzymes exhibited varying degrees of activities,
      generally corresponding to the phenotypes with which they are associated. The
      results presented demonstrate the use of the vaccinia virus-derived expression
      system and of loading living cells with fluorescent substrate as efficient tools
      for studying mutants in Gaucher disease and in other lysosomal diseases.

PMID- 9175736
TI  - Evolutionary silencing of the human elastase I gene (ELA1).
AB  - The human pancreatic elastase I gene is transcriptionally silent, despite the
      apparent integrity of the structural gene. The transcriptional regulatory
      sequences necessary and sufficient for transcription of the active rat homologue
      are localized within 205 base pairs (bp) of the transcriptional start and
      comprise a pancreas-specific transcriptional enhancer of 134 bp immediately
      upstream of a 71 bp non-specific promoter. The human gene has 58 nucleotide
      differences within this region, 13 of which are in the three functional elements
      (A, B and C) that constitute the enhancer. Through cell transfection analyses
      with a pancreatic acinar tumor cell line, we show that the nucleotide differences
      in the human 5' flanking gene sequences have inactivated both the enhancer and
      the promoter. The changes in the three elements of the human enhancer alone are
      sufficient to inactivate the enhancer; conversely, restoring these to the rat
      configuration partially restores the activity of the human enhancer. The two
      mutations in the A element and the four mutations in the B element abolish the
      binding of the transcription factors previously shown to mediate the activity of
      these elements. Replacing the active 71 bp rat promoter with the human promoter
      also prevents expression. Therefore, the evolutionary silencing of the human
      elastase I gene appears due to mutations that inactivate crucial enhancer and
      promoter elements.

PMID- 9175737
TI  - Advanced telomere shortening in respiratory chain disorders.
AB  - Cell and tissue damage in respiratory chain disorders have been related to
      increased production of reactive oxygen species (ROS). We measured telomere
      lengths in such disorders since ROS have also been implicated with telomere
      shortening. We investigated whole blood cell DNA of 14 patients with MELAS
      related mitochondriopathy and two patients with the LHON-associated G11778A
      mutation of the mitochondrial genome. The phenotypes were variable and included
      an unusual case of schizophrenia-like psychosis associated with the A3243G
      mutation. As compared to healthy controls telomere shortening in the patient
      group was advanced (P < or = 0.006). We compare this finding with the accelerated
      telomere shortening in Down's syndrome and in chromosomal breakage syndromes. We
      discuss possible relations between advanced telomere shortening and selective
      constraints that act on proliferating cells with respiratory chain dysfunction.

PMID- 9175739
TI  - A novel candidate tumour suppressor locus at 9q32-33 in bladder cancer:
      localization of the candidate region within a single 840 kb YAC.
AB  - Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic
      alteration in transitional cell carcinoma (TCC) of the bladder, implicating the
      presence of a tumour suppressor gene or genes on 9q. To define the location of a
      tumour suppressor locus on 9q in TCC, we screened 156 TCCs of the bladder and
      upper urinary tract by detailed deletion mapping using 31 microsatellite markers
      on 9q. Partial deletions of 9q were found in 10 TCCs (6%), and LOH at all
      informative loci on 9q was found in 77 TCCs (49%). In five low grade superficial
      bladder tumours, the partial deletion was localized to D9S195 located at 9q32-33,
      with retention of heterozygosity at all other informative loci including D9S103,
      D9S258, D9S275 and GSN. We constructed a yeast artificial chromosome (YAC) contig
      covering the deleted region in these five tumours and placed another four
      unmapped microsatellite markers on this contig map. Using these markers, we
      further defined the common deleted region to the interval between D9S1848 and
      AFMA239XA9. The region is covered by a single YAC (852e11), whose size is
      estimated to be 840 kb. Our data should expedite further fine mapping and
      identification of the candidate tumour suppressor gene at 9q32-33.

PMID- 9175738
TI  - A novel mechanism of aberrant pre-mRNA splicing in humans.
AB  - Eukaryotic pre-mRNA splicing is regulated by consensus sequences at the intron
      boundaries and branch site. Recently, Sirand-Pugnet et al. reported the
      importance of an additional intronic sequence, an (A/U)GGG repeat in chicken beta
      tropomyosin that is a binding site for a protein required for spliceosome
      assembly. Interestingly, we have detected mutations in IVS3 of the human growth
      hormone (GH) gene that affect a putative, homologous consensus sequence and which
      also perturb splicing. In a series of dominant-negative GH mutations that cause
      exon skipping, we found two mutations that do not occur within the 5' and 3'
      splice sites, or branch consensus sites. The first mutation is a G-->A transition
      of the 28th base (+28G-->A) of and the second deletes 18 bp (del+28-45) of IVS3
      of the human GH gene. These mutations segregated with autosomal dominant GH
      deficiency in both kindreds and no other allelic GH gene changes were detected.
      RT-PCR amplification of transcripts from expression vectors containing the +28G-
      >A or del+28-45 alleles yielded products showing a >10-fold preferred use of
      alternative splicing, similar to findings previously reported for IVS3 donor site
      mutations. Both mutations are located 28 bp downstream from the 5' splice site
      and examination of the sequences perturbed revealed an intronic XGGG repeat
      similar to the repeat found to regulate mRNA splicing in chicken beta
      tropomyosin. Interestingly, the XGGG repeats involved in our mutations exhibit
      homologous spacing to those in a so-called 'winner' RNA sequence. Binding of A1
      heterogeneous nuclear ribonucleoprotein (hnRNP) by 'winner' sequences in pre-mRNA
      transcripts is thought to play an important role in pre-mRNA packaging and
      transport as well as 5' splice site selection in pre-mRNAs that contain multiple
      5' splice sites. Our findings suggest that (i) XGGG repeats may regulate
      alternative splicing in the human GH gene and (ii) mutations of these repeats
      cause GH deficiency by perturbing alternative splicing. Mutations of homologous
      intron sequences may underlie other human diseases.

PMID- 9175740
TI  - The telomere lengthening mechanism in telomerase-negative immortal human cells
      does not involve the telomerase RNA subunit.
AB  - According to the telomere hypothesis of senescence, the progressive shortening of
      telomeres that occurs upon division of normal somatic cells eventually leads to
      cellular senescence. The immortalisation of human cells is associated with the
      acquisition of a telomere maintenance mechanism which is usually dependent upon
      expression of the enzyme telomerase. About one third of in vitro immortalised
      human cell lines, however, have no detectable telomerase but contain telomeres
      that are abnormally long. The nature of the alternative telomere maintenance
      mechanism (referred to as ALT, for Alternative Lengthening of Telomeres) that
      must exist in these telomerase-negative cells has not been elucidated. It has
      previously been shown that abnormal lengthening of yeast telomeres may occur due
      to mutations in the yeast telomerase RNA gene. That this is not the mechanism of
      the abnormally long telomeres in ALT cell lines was demonstrated by the finding
      that seven of seven ALT lines have wild-type human telomerase RNA (hTR) sequence,
      including a novel polymorphism that is present in 30% of normal individuals. We
      found that two ALT cell lines have no detectable expression of the hTR gene. This
      shows that the ALT mechanism in these cell lines is not dependent on hTR.
      Expression of exogenous hTR via infection of these cells with a recombinant hTR
      adenovirus vector did not result in telomerase activity, indicating that their
      lack of telomerase activity is not due to absence of hTR expression. We conclude
      that the ALT mechanism is not dependent on the expression of hTR, and does not
      involve mutations in the hTR sequence.

PMID- 9175741
TI  - A model of corrective gene transfer in X-linked ichthyosis.
AB  - Single gene recessive genetic skin disorders offer attractive prototypes for the
      development of therapeutic cutaneous gene delivery. We have utilized X-linked
      ichthyosis (XLI), characterized by loss of function of the steroid sulfatase
      arylsulfatase C (STS), to develop a model of corrective gene delivery to human
      skin in vivo. A new retroviral expression vector was produced and utilized to
      effect STS gene transfer to primary keratinocytes from XLI patients. Transduction
      was associated with restoration of full-length STS protein expression as well as
      steroid sulfatase enzymatic activity in proportion to the number of proviral
      integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along
      with normal controls, were then grafted onto immunodeficient mice to regenerate
      full thickness human epidermis. Unmodified XLI keratinocytes regenerated a
      hyperkeratotic epidermis lacking STS expression with defective skin barrier
      function, effectively recapitulating the human disease in vivo. Transduced XLI
      keratinocytes from the same patients, however, regenerated epidermis
      histologically indistinguishable from that formed by keratinocytes from patients
      with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by
      immunostaining as well as a normalization of histologic appearance at 5 weeks
      post-grafting. In addition, transduced XLI epidermis demonstrated a return of
      barrier function parameters to normal. These findings demonstrate corrective gene
      delivery in human XLI patient skin tissue at both molecular and functional levels
      and provide a model of human cutaneous gene therapy.

PMID- 9175742
TI  - Molecular mechanisms in mitochondrial DNA depletion syndrome.
AB  - Depletion of mitochondrial DNA (mtDNA) appears to be an important cause of
      mitochondrial dysfunction in neonates and infants. We have identified another
      child in whom depletion of mtDNA was demonstrated in liver and serial skeletal
      muscle biopsies. A primary myoblast culture from the patient initially showed
      normal levels of mtDNA, but there was a progressive loss of mtDNA in later cell
      passages and clonal myoblast cell cultures, similar to that observed in the
      skeletal muscle tissue of the patient. Thus, these clonal myoblast cultures
      provide an in vitro model of the in vivo mtDNA dynamics. The levels of
      mitochondrial mRNAs for subunits I and II of cytochrome c oxidase declined with
      declining mtDNA levels, but the fall in mitochondrial transcript levels lagged
      behind that of the mtDNA levels. Levels of cytochrome c oxidase subunit I and II
      polypeptides, however, declined ahead of declining mtDNA levels.
      Immunocytochemistry showed that between individual cells of the clonal myoblast
      cultures, the expression of the mitochondrially encoded subunit I of cytochrome c
      oxidase was heterogeneous, suggesting variable levels of mtDNA. Transfer of
      patient mitochondria with residual mtDNA levels to control cells devoid of mtDNA
      (rho0 cells) led to restoration of mtDNA levels and, hence, suggests a nuclear
      involvement in the depletion.

PMID- 9175743
TI  - An insertion mutation of the CHRNA4 gene in a family with autosomal dominant
      nocturnal frontal lobe epilepsy.
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is the first, and to
      date only, idiopathic epilepsy for which a specific mutation has been found. A
      missense mutation in the critical M2 domain of the alpha4 subunit of the neuronal
      nicotinic acetylcholine receptor (CHRNA4) has been recently identified in one
      large Australian pedigree. Here we describe a novel mutation in the M2 domain of
      the CHRNA4 gene in a Norwegian family. Three nucleotides (GCT) were inserted at
      nucleotide position 776 into the coding region for the C-terminal end of the M2
      domain. Physiological investigations of the receptor reconstituted with the
      mutated CHRNA4 subunit reveal that this insertion does not prevent the receptor
      function but increases its apparent affinity for ACh. In addition, this mutant
      receptor shows a significantly lower calcium permeability that, at the cellular
      level, may correspond to a loss of function. Comparison of the two mutations
      identified so far in families with ADNFLE illustrates that different mutations
      can result in similar phenotypes.

PMID- 9175744
TI  - A translation frameshift mutation induced by a cytosine insertion in the
      polycystic kidney disease 2 gene (PDK2).
AB  - Mutations in the PKD2 gene on the long arm of chromosome 4 are responsible for
      approximately 15% of cases of polycystic kidney disease. Perhaps the only
      difference from the more common ADPKD1 cases is the rate of progression of cystic
      changes, and the age of onset, which is 10-15 years later for the ADPKD2 form. In
      Cyprus there are at least three large families, documented by molecular linkage
      analysis, that map to the PKD2 locus. For two of them the defects were recently
      shown to be nonsense mutations at positions arginine 742 and glutamine 405. In
      this report, we describe the mutation in the third family, CY1602. For this, the
      entire coding sequence was systematically screened by single strand conformation
      analysis and heteroduplex formation. A novel mutation was identified in exon 2
      where a new cytosine residue was inserted immediately after codon 231 (231insC).
      It causes a translation frameshift and is expected to lead to the introduction of
      37 novel amino acids before the translation reaches a new STOP codon. It is the
      most amino terminal mutation reported to date, and based on the protein's modeled
      structure, is predicted to be within the first transmembrane domain. It is the
      fourth PKD2 mutation reported thus far, and the first which is not a nonsense
      mutation.

PMID- 9175745
TI  - A genome wide search for susceptibility loci in three European malignant
      hyperthermia pedigrees.
AB  - Malignant hyperthermia (MH) is an autosomal dominant disorder which is
      potentially lethal in susceptible individuals on exposure to commonly used
      inhalational anaesthetics and depolarising muscle relaxants. Crises reflect the
      consequences of disturbed skeletal muscle calcium homeostasis. Susceptibility was
      first localised to chromosome 19q13.1 and the skeletal muscle ryanodine receptor,
      RYR1 (the calcium release channel of the sarcoplasmic reticulum). Defects in this
      gene have been identified which cosegregate with the MHS phenotype and evidence
      as to their potential causal roles has accumulated. MH has, however, been shown
      to be genetically heterogeneous, additional loci on chromosomes 3q, 17q and 7q
      being proposed. Pedigrees remain in Europe where linkage status is still unclear.
      In a collaborative search of the human genome conducted with three pedigrees
      whose disease status was classified according to the European IVCT protocol we
      have evidence to suggest that at least two further loci exist for MH
      susceptibility. One of these locates to chromosome 1q, the site of a candidate
      gene, CACNL1A3, encoding the alpha-subunit of the dihydropyridine receptor. The
      second region resides on chromosome 5p to where no known candidate has been
      mapped to date. The third family exhibited inconclusive results which suggests
      the existence of at least one other locus. This study adds to the evidence for
      considerable genetic heterogeneity in MH and will provide a route to further our
      understanding of the molecular pathology of the condition.

PMID- 9175746
TI  - 'Late onset' ornithine transcarbamylase deficiency: function of three purified
      recombinant mutant enzymes.
AB  - Although many mutations in the ornithine transcarbamylase gene have been
      correlated with 'late onset' of hyperammonemia in patients, the effects of these
      mutations on enzyme function are largely unknown. Three recurrent mutations
      (R40H, R277W and R277Q) found in patients with 'late onset' disease were
      incorporated into 'mature' human ornithine transcarbamylase cDNA and
      overexpressed in Escherichia coli. The three recombinant mutant enzymes were
      purified to homogeneity on an affinity column and their biochemical
      characteristics were compared to the wild type enzyme. The R277W and R277Q
      mutants display markedly reduced affinity for L-ornithine, loss of substrate
      inhibition, alkaline shift of pH optimum, and reduced thermal stability compared
      to the wild type enzyme. These differences, particularly the reduced affinity for
      L-ornithine, are sufficient to account for their biochemical effects. In
      contrast, the 'mature' R40H mutant was biochemically indistinguishable from the
      wild type enzyme in vitro.

PMID- 9175747
TI  - Dynamin II associates with Grb2 SH3 domain in Ras transformed NIH3T3 cells.
AB  - Grb2, a linker protein containing two SH3 domains and one SH2 domain, is known as
      an essential element of the Ras pathway in multiple systems. One of the functions
      of Grb2 is to link tyrosine-phosphorylated receptors to downstream effector
      proteins via the SH2 and SH3 domain bindings. To identify Grb2-associated
      proteins in Ras transformed NIH3T3 cells, we performed coprecipitation
      experiments using recombinant GST-Grb2 fusion proteins and found a remarkably
      strong band of 100 kDa. With N-terminal amino acid sequencing, we identified the
      protein of 100 kDa as dynamin II. Dynamin II was also observed in the
      coprecipitates with the GST fusion protein of N-SH3 or C-SH3 domain of Grb2 but
      not in that of Grb2 SH2 domain. The SH3-mediated association of Grb2 with dynamin
      II was confirmed by competitive binding experiments with oligopeptides whose
      sequence corresponded to that of SH2 or SH3 binding motif. The dynamin II
      coprecipitation was completely abrogated by the addition of the oligopeptide of
      SH3 binding motif, but addition of SH2 binding motif had no effect. In
      conclusion, these results suggest that dynamin II may be largely expressed and
      closely associated with Grb2-mediated signaling in Ras transformed cells.

PMID- 9175748
TI  - Gene expression of a protein, JB70, related to rat alpha1-acid glycoprotein in
      Euglena gracilis.
AB  - Antibodies directed against rat alpha1-acid glycoprotein (AGP) recognize a 70 kDa
      antigen, designated JB70, present in extracts of achlorophyllous Euglena gracilis
      cells as well as in their culture medium. By using 2-dimensional electrophoresis,
      JB70 appears to be composed of two acidic polypeptides. Additionally, Northern
      blot analysis reveals the presence in E. gracilis cells of a 2.3 kb mRNA
      hybridizing with a cDNA probe specific for rat AGP mRNA. Moreover, elevated mRNA
      levels are detected in dexamethasone-treated E. gracilis cells, indicating a
      response to this inducer similar to that observed for hepatic AGP. These results
      strongly suggest that polypeptides closely related to hepatic rat AGP are
      expressed in E. gracilis cells. They also indicate that, like other gene families
      implicated in natural defense processes such as heat-shock protein and
      metallothionein genes, the AGP gene appears to be conserved down to this early
      diverging eucaryote.

PMID- 9175749
TI  - Soluble overexpression in Escherichia coli, and purification and characterization
      of wild-type recombinant tobacco acetolactate synthase.
AB  - Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of L
      leucine, L-isoleucine, and L-valine. The wild-type ALS gene from Nicotiana
      tabacum was cloned into the bacterial expression vector pGEX-2T. The resulting
      recombinant plasmid pGEX-ALS2 was used to transform Escherichia coli strain XL1
      Blue, and the wild-type tobacco ALS (wALS) was expressed in the bacteria as a
      protein fused with glutathione S-transferase (GST). The fusion product GST-wALS
      was purified in a single step on a glutathione-Sepharose column. The purified GST
      wALS was sensitive to a sulfonylurea herbicide, and was lost its sensitivity to
      end products, L-valine, L-leucine and L-isoleucine. These results suggest that
      the purified recombinant tobacco ALS was functionally active, and that the
      sulfonylureas may not bind to the feedback regulatory site on the plant ALS.

PMID- 9175750
TI  - 6-sulfooxymethylbenzo[a]pyrene is an ultimate electrophilic and carcinogenic form
      of the intermediary metabolite 6-hydroxymethylbenzo[a]pyrene.
AB  - Previous experiments have demonstrated that the intermediary metabolite 6
      hydroxymethylbenzo[a] pyrene (HMBP) can be activated to the electrophilic
      mutagen, 6-sulfooxymethylbenzo[a]pyrene (SMBP), by rat and mouse liver PAPS
      dependent sulfotransferase activity or by chemical synthesis. This aralkylating
      metabolite and 6-hydroxymethylbenzo[a]pyrene were individually administered to
      groups of 12 female Sprague-Dawley rats, at a 0.2 micromol dose three times
      weekly for 20 doses. SMBP induced sarcomas at the site of injection in 12 of 12
      rats by 33 weeks, whereas HMBP induced sarcomas at the site of injection in 12 of
      12 rats by 31 weeks. These results, taken together with the results of previous
      studies, strongly support the hypothesis that the electrophilic mutagen SMBP
      accounts for most, if not all, of the complete carcinogenicity of the
      intermediary metabolite HMBP and probably at least some of the complete
      carcinogenicity of 6-methylbenzo[a]pyrene (MBP), 6-formylbenzo[a]pyrene
      (formylBP), and even benzo[a]pyrene (BP), all of which are metabolized to HMBP.

PMID- 9175751
TI  - Metabolic changes of E-selectin caused by the binding of a mucin carrying
      sialylLewis A antigens.
AB  - Mucin-type glycoproteins carrying sialylLeA antigens (SL-GP) were isolated from
      the ascites fluid of a patient with colorectal cancer. SL-GP bound to E-selectin
      on endothelial cells in Ca2+- and sialylLeA antigen-dependent manners. To examine
      the metabolic change in E-selectin caused by ligation, endothelial cells were
      labeled with 32P-phosphate or 35S-Met and 35S-Cys. Phosphorylation at one or more
      serine residues of E-selectin was elevated by ligation with SL-GP but not with
      sialylLeA hexasaccharide. Pulse-labeling of E-selectin with 35S-Met and 35S-Cys
      in the presence of SL-GP indicated that the degradation of E-selectin was
      accelerated by SL-GP ligation, but labeling after pre-ligation with SL-GP
      revealed an increase in the synthesis of E-selectin. The synthesis may reflect
      compensation for the E-selectin degraded on pre-ligation. These results indicate
      that the overall metabolism of E-selectin was enhanced by the ligation of SL-GP,
      with degradation and synthesis being apparently balanced.

PMID- 9175752
TI  - Expression of the Escherichia coli thioredoxin gene is negatively regulated by
      cyclic AMP.
AB  - Regulation of the Escherichia coli thioredoxin gene (trxA) was studied using trxA
      lac translational fusion constructed in the vector pMC1403. Synthesis of beta
      galactosidase from the trxA-lac fusion was found to be repressed in the presence
      of lactose. A switch of carbon source from glucose to lactose and an addition of
      cyclic AMP (cAMP) caused a decrease in beta-galactosidase synthesis from the trxA
      lac fusion. The repression effect of exogenous cAMP was not observed in the crp
      mutant strain. The beta-galactosidase synthesis from the trxA-lac fusion lacking
      a plausible cAMP-CRP binding site was not lowered in the presence of lactose or
      in the addition of cAMP. Expression of the chromosomal trxA gene was reduced by
      exogenous cAMP. These findings indicate that the expression of the trxA gene is
      controlled by cAMP in a negative manner.

PMID- 9175753
TI  - A possible mechanism for hyperthermic radiosensitization mediated through
      hyperthermic lability of Ku subunits in DNA-dependent protein kinase.
AB  - DNA-dependent protein kinase (DNA-PK), composed of p470 catalytic subunit and
      p85/p70 heterodimer of Ku autoantigen, is considered a critical enzyme in DNA
      double-strand break repair. We purified DNA-PK from human leukaemic MOLT-4 cells
      by successive column chromatography and separated into p470 and Ku subunits by
      ultracentrifugation in glycerol gradient. We studied hyperthermic stability of
      DNA-PK holoenzyme and its separated subunits to test a possible role of DNA-PK in
      hyperthermic radiosensitization. DNA-PK was found to lose its activity rapidly at
      hyperthermic 44 degrees C, and further, Ku subunits instead of p470 catalytic
      subunits were found to be sensitive to hyperthermia. These results indicate a
      possibility that hyperthermic radiosensitization is mediated through the heat
      lability of Ku subunits of DNA-PK, impairing repair of radiation-induced double
      strand break of DNA.

PMID- 9175754
TI  - Deficient apoptotic process in cisplatin-resistant L1210 cells cannot account for
      the cellular response to various drug treatments.
AB  - Apoptosis is a major determinant of the effectiveness of antitumor chemotherapy
      since most of the drugs used in cancer treatment provoke cell death by this
      process. We selected L1210/0.7R (7-fold) and L1210/3R (16-fold) murine leukemia
      cells resistant to cisplatin (CDDP) by adaptation of parental L1210/S cells to
      increasing drug concentration. L1210/0.7R exhibited a decreased apoptosis
      response to CDDP compared to parental L1210/S, while it was totally defective in
      L1210/3R as analyzed by cell morphology, DNA fragmentation, and poly(ADP-ribose)
      polymerase cleavage. This default in apoptosis did not result from differential
      expression of the antiapoptotic protein bcl-2 or from altered expression of p53.
      L1210/3R was resistant to other cross-linking agents and sensitive to
      topoisomerase II inhibitors and microtubule poisons. Whatever the drug
      sensitivity phenotype to these agents, L1210/3R was totally defective in
      apoptosis in response to drug treatment, showing that apoptosis control cannot be
      directly involved in the resistance process of these cell lines.

PMID- 9175755
TI  - Structure of catechol 2,3-dioxygenase gene encoded in TOM plasmid of Pseudomonas
      cepacia G4.
AB  - The catechol 2,3-dioxygenase is an extradiol-type dioxygenase which cleaves the C
      C bond at the meta position of catechol to form 2-hydroxymuconic semialdehyde. A
      catechol 2,3-dioxygenase gene (tomB) in the TOM plasmid of P. cepacia G4 has been
      cloned and its nucleotide sequence was analyzed. The enzyme gene consisted of 945
      base pairs with an ATG initiation codon and a TGA termination codon which can
      encode a polypeptide of molecular weight 35 kDa containing 314 amino acid
      residues, and a putative ribosome-binding sequence was identified at
      approximately 10 nucleotides upstream of the initiation codon. The deduced amino
      acid sequence of catechol 2,3-dioxygenase from P. cepacia G4 exhibited 79-82%
      homologies with those of 3-methylcatechol 2,3-dioxygenase of P. putida UCC2 and
      catechol 2,3-dioxygenase of P. pickettii PKO1.

PMID- 9175756
TI  - Identification of a new phosphorylation site in cardiac muscle
      phosphofructokinase.
AB  - The novel phosphorylation site (Ser376) that we discovered during in vitro
      studies of the troponin C- or calmodulin-induced phosphorylation of rabbit muscle
      phosphofructokinase [Zhao, Z., Malencik, D.A., and Anderson, S. R. (1991)
      Biochemistry 30, 2204] also undergoes phosphorylation in the epinephrine
      stimulated rabbit heart. Reversed-phase HPLC and/or iron chelate affinity
      chromatography performed on CNBr digests of phosphofructokinase that had been
      isolated from epinephrine-treated hearts yields a largely phosphorylated peptide
      corresponding to amino acid residues 371-378 of the enzyme. Mass spectrometry,
      gas phase sequencing, and amino acid analyses establish the structure and
      phosphorylation state of the peptide.

PMID- 9175757
TI  - Expression of glutathione and gamma-glutamylcysteine synthetase mRNA is Jun
      dependent.
AB  - The gene GLCLC encodes the catalytic subunit of gamma-glutamylcysteine synthetase
      (glutamate-cysteine ligase E.C. 6.3.2.2), the rate limiting enzyme for
      glutathione synthesis. When HepG2 cells were exposed to the serine/threonine
      phosphatase inhibitor okadaic acid (OA), increased expression of GLCLC was
      observed, as was the development of resistance to xenobiotic induced GSH
      depletion. Okadaic acid is known to activate both NF-kappaB and AP-1 activity.
      Inhibition of NF-kappaB activity by overexpression of an IkappaB alpha
      transdominant inhibitor or exposure to the protease inhibitor TLCK did not
      inhibit the OA mediated increase in GLCLC transcripts. Fibroblasts derived from a
      mouse containing a c-Jun null mutation exhibited diminished AP-1 binding
      activity, reduced levels of GLCLC message, and a correspondingly low GSH
      concentration compared to wild type cells. When the null cells, which express Jun
      B and Jun D, were exposed to OA, AP-1 binding activity increased, as did
      expression of GLCLC message. These results indicate that AP-1 transcription
      factors participate in the regulation of glutathione metabolism.

PMID- 9175758
TI  - RGD-containing peptides trigger apoptosis in glomerular mesangial cells of adult
      human kidneys.
AB  - Substantial evidence was given that different Arg-Gly-Asp (RGD)-containing
      peptides, linear Arg-Gly-Asp-Ser (RGDS) and cyclic Arg-Gly-Asp-Phe (RGDF), which
      are sequences present in fibronectin and vitronectin and which can bind
      alpha5beta1 and alpha(v)beta3 integrins, respectively, both induced apoptosis and
      expression of interleukin-1beta-converting enzyme (ICE) in cultured glomerular
      mesangial cells from adult human kidneys, with consistent apoptosis features
      appearing as nuclei condensation and fragmentation, internucleosomal DNA
      fragmentation, and DNA content decrease. These results indicated that both
      fibronectin and vitronectin may be important in the survival of human glomerular
      mesangial cells and that stable cyclic RGD(D)FV peptide may be a candidate to be
      used for regulating apoptosis in vivo.

PMID- 9175759
TI  - Concanavalin A directly stimulates bone-resorbing activity of osteoclasts and
      their gene expression of cathepsin K/OC-2.
AB  - Concanavalin A (Con A), a plant lectin that recognizes cell-surface
      glycoproteins, up-regulates osteoclastic bone-resorbing activity of cultured
      isolated rabbit pure osteoclasts as well as unfractionated bone cells. The effect
      of Con A was blocked by alpha-methyl mannopyranoside. Several Con A-binding
      proteins were detected in the plasma membranes from osteoclasts. Furthermore, Con
      A increased the levels of transcripts of cathepsin K/OC-2, one of the proteases
      responsible for osteoclastic bone-resorbing activity. These results indicate that
      Con A directly enhances the function of osteoclasts by the association with
      surface glycoproteins of osteoclasts.

PMID- 9175760
TI  - Regulation by thyroid hormone and retinoic acid of the CCAAT/enhancer binding
      protein alpha and beta genes during liver development.
AB  - The effect of thyroid hormone and retinoic acid on the expression of
      CCAAT/enhancer binding proteins (C/EBPs) alpha and beta was investigated in rat
      liver during development. Congenital hypothyroidism caused a significant decrease
      in both C/EBP alpha and C/EBP beta gene expression at early stages of postnatal
      development. This effect was tissue specific since thyroid hormone had no effect
      on the level of C/EBP mRNAs in brown fat. Injection of 15-, and 30-day-old
      hypothyroid animals with thyroid hormone resulted in a slow recovery of the
      hepatic levels of both C/EBP alpha and beta mRNA levels. Retinoic acid was a very
      rapid and potent stimulator compared to thyroid hormone in hypothyroid animals.
      C/EBP alpha and beta protein levels were markedly diminished in hypothyroid
      neonates and the kinetics of induction of these proteins by thyroid hormone was
      faster than the one observed for the corresponding transcripts. The discrepancies
      observed between mRNA and protein levels suggest a translational or post
      translational regulation of these genes as the major point of thyroid hormone
      action on these genes.

PMID- 9175761
TI  - Activation of c-Jun N-terminal kinase by human granulocyte macrophage-colony
      stimulating factor in BA/F3 cells.
AB  - Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces various
      signaling events in hematopoietic cells. We reported that there are at least two
      distinct pathways of hGM-CSF signals, one for activation of proliferation and the
      other one for activation of c-fos promoter through the MAPK cascade. Activation
      of other members of the MAPK family, c-Jun N-terminal kinase (JNK) and p38 MAPK
      under various cellular stress have also been reported. We found that hGM-CSF
      activates JNK in BA/F3 cells expressing the hGM-CSF receptor (hGMR) and that
      activation depends on a membrane proximal region including box1 and requires a
      more membrane distal region of hGMR beta subunit (beta c). There are 8 known
      tyrosine (tyr) residues in the cytoplasmic region of beta c. Mutant beta c
      lacking all the tyr residues hardly activates JNK, thereby indicating that the
      tyr residue(s) is essential for the activation of JNK. Mutation analyses of each
      tyr residue indicated that none of the tyr residues seems essential for the
      activation of JNK, indicating multiple tyr residues play a similar function to
      transduce signals for this activation.

PMID- 9175762
TI  - The proto-oncogene Crk-II enhances apoptosis by a Ras-dependent, Raf-1/MAP kinase
      independent pathway.
AB  - Human embryonic kidney 293 cells and 293 cells overexpressing different amounts
      of the adaptor protein Crk-II (ranging from 3- to 10-fold higher levels than the
      parental cell line) were examined for their ability to undergo apoptosis when
      maintained in control and serum-free (SF) medium. Parental 293 cells undergo
      apoptosis only when deprived of serum for prolonged periods of time (24-48 h). On
      the other hand, 293 cells overexpressing different levels of Crk-II present
      detectable levels of apoptosis as measured by DNA fragmentation when grown in
      control medium, with a marked increase when they are deprived of serum for 12-48
      h. To determine the pathways involved in Crk-II-induced apoptosis, Crk-II
      overexpressing cells were transiently transfected with a dominant-negative Ras
      construct (N17-Ras). Compared to cells transfected with control vectors, the
      cells overexpressing N17-Ras presented lower levels of apoptosis when maintained
      in SF-medium. On the other hand, transient transfection of a dominant-negative
      Raf-1 construct (K375W-Raf-1) did not decrease apoptosis; slightly increasing DNA
      fragmentation levels were seen. Similar results were obtained when the cells were
      incubated in the presence of a MEK1 inhibitor. The results presented here suggest
      that overexpression of Crk-II induces apoptosis via a Ras-dependent, Raf
      1/MEK1/ERK-independent pathway.

PMID- 9175763
TI  - Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein
      by PKN.
AB  - PKN is a serine/threonine protein kinase with a catalytic domain homologous to
      the protein kinase C family and unique N-terminal leucine zipper-like sequences.
      Using analyses with the yeast two-hybrid system and in vitro binding assay, we
      found that the regulatory domain of PKN interacted with vimentin. We then
      examined whether PKN would phosphorylate vimentin in vitro. Vimentin proved to be
      an excellent substrate for PKN, and the phosphorylation of vimentin by PKN
      occurred in the head domain with the result of a nearly complete inhibition of
      its filament formation in vitro. Similar results were also obtained with another
      type III intermediate filament protein, glial fibrillary acidic protein (GFAP).
      These results raise the possibility that PKN may regulate filament structures of
      vimentin and GFAP by domain-specific phosphorylation.

PMID- 9175764
TI  - Defects of insulin and IGF-1 action at receptor and postreceptor level in a
      patient with type A syndrome of insulin resistance.
AB  - The action of insulin and IGF-1 in comparison to non-diabetic controls was
      studied in cultured fibroblasts of a patient with an inherited syndrome of
      insulin resistance (Type A syndrome). Insulin binding was reduced due to
      decreased receptor affinity, but sequence analyses revealed no alterations of
      splicing or primary insulin receptor (IR) structure. Most likely due to the IR
      affinity defect analyses of signal transduction pathways showed an impairment of
      insulin action on glucose uptake, total RNA synthesis and phosphorylation as well
      as activity of MAP-kinase. In addition inducibility of c-fos mRNA level was
      strongly impaired by insulin and IGF-1, but comparable to controls by PDGF
      indicating a postreceptor defect. In conclusion, we provide evidence that genetic
      syndromes of insulin resistance can be associated with both, receptor and
      postreceptor defects.

PMID- 9175765
TI  - Two isoforms of prostaglandin EP3 receptor exhibiting constitutive activity and
      agonist-dependent activity in Rho-mediated stress fiber formation.
AB  - We have cloned two isoforms of the mouse prostaglandin E receptor EP3 subtype,
      EP3alpha and EP3beta, with different carboxyl-terminal tails, produced through
      alternative splicing. To determine the functional differences between the two
      isoforms, we examined the role of the isoforms in regulation of the actin
      cytoskeleton using Mardin-Darby canine kidney cells expressing these isoforms.
      The EP3alpha isoform constitutively induced stress fiber formation, independent
      of an agonist, while the EP3beta isoform agonist-dependently induced stress fiber
      formation. Pertussis toxin did not prevent stress fiber formation. This signaling
      pathway is mediated by Rho, because C3 transferase microinjection inhibited
      stress fiber formation. Therefore, the physiological significance of these
      isoforms of the EP3 receptor may lie in their different agonist dependency in Rho
      mediated stress fiber formation via a pertussis toxin-insensitive G protein.

PMID- 9175766
TI  - Heparin alters transdermal transport associated with electroporation.
AB  - Short, high-voltage (HV; U(skin,max) approximately 100 V) pulses have been shown
      to increase rates of transdermal transport by several orders of magnitude via a
      mechanism hypothesized to involve electroporation. We show that heparin, a
      linear, highly charged macromolecule, significantly alters the molecular
      transport capacity and lifetime of aqueous pathways across human stratum corneum
      (SC) created by such pulses. If co-transported during pulsing, heparin molecules
      can interact with the SC and other molecules, thereby altering ionic and
      molecular transport. We also observed an increase in post-pulse skin permeability
      and persistent lower skin resistance. Because most heparin molecules are long
      enough to span the five to six lipid bilayer membranes that separate corneocytes
      within the SC, these results can be explained by the hypothesis that heparin
      molecules were trapped within the skin, holding open pathway segments connecting
      adjacent corneocytes. These results support the skin electroporation hypothesis
      and provide the first demonstration of a chemical enhancer effect for transdermal
      transport by HV pulsing.

PMID- 9175767
TI  - Geranylgeraniol potently induces caspase-3-like activity during apoptosis in
      human leukemia U937 cells.
AB  - In a previous study, we showed that geranylgeraniol (GGO) is a potent inducer of
      apoptosis in human leukemia cells. The present study describes the effects of GGO
      on the activity of cysteine-dependent aspartate-directed proteases (caspases) in
      human leukemia U937 cells. The caspase-3 (CPP32) activity was increased in a time
      dependent manner by treatment with 50 microM GGO, whereas no activation of
      caspase-1 (interleukin-1beta converting enzyme (ICE)) was observed in any time
      period under the same experimental conditions. Other isoprenyl compounds such as
      geraniol, geranylgerany-lacetone, and vitamin K2 had no measurable effects on the
      activities of either caspase-3 or caspase-1. A inhibitor that preferentially
      inhibits the caspase-3 related caspases, Z-DEVD-FMK, strongly blocked the GGO
      induced DNA fragmentation. These results suggest the involvement of caspase-3 in
      GGO-induced apoptosis in U937 human leukemia cells.

PMID- 9175768
TI  - Sea urchin mitochondrial matrix contains a 56-kDa chaperonine-like protein.
AB  - Paracentrotus lividus mitochondrial matrix contains a constitutive hsp of 56-KDa
      which cross reacts with a serum anti-hsp-60 chaperonine from yeast mitochondria.
      The localization of hsps preexisting or newly synthesized in different
      subcellular fractions of gastrula embryos is also analyzed by two-dimensional
      electrophoresis.

PMID- 9175769
TI  - Encapsulation of flavodoxin in reverse micelles.
AB  - The regulation of the properties of Desulfovibrio gigas flavodoxin in
      AOT/water/iso-octane micellar system was studied. UV-visible spectroscopic
      studies have shown that photoreduction of flavodoxin in the presence of EDTA
      leads to hydroquinone formation through the intermediate semiquinone. The [free
      FMN] - [bound to flavodoxin FMN] equilibrium (and hence, the amount of
      apoprotein) depends on redox state of FMN and on hydration degree which controls
      the micellar size. Thus, a new method of reversible cofactor removing under mild
      conditions (at low hydration degree of micelles) is suggested, accompained by
      isolation of apo-form of the protein.

PMID- 9175770
TI  - Joint cultivation of human erythroblastoid cells and mouse fibroblasts triggers
      release of a wide spectrum of cytotoxic factors.
AB  - It has been demonstrated that joint cultivation of human K-562 cells and mouse L
      929 cells results in triggering apoptosis in L-929 cells and possibly also in K
      562 cells. Analysis of proteins recovered from the culture medium has revealed
      the presence of three cytotoxic factors including TNF-alpha. This is the first
      observation of a release of cytotoxic factors by non-lymphoid cells in response
      to a direct contact with cells of different origin.

PMID- 9175771
TI  - The solution structure of a class II major histocompatibility complex
      superantigen binding domain.
AB  - We have used 600 MHz 1H NMR spectroscopy data to determine the solution structure
      of a 31-residue domain of a murine class II major histocompatibility (MHC)
      protein. This domain, I-Ab(beta)-(60-90), binds to the superantigen
      staphylococcal enterotoxin A. Distance geometry and dynamical simulated annealing
      calculations were performed using NOESY- and COSY-deduced constraints. I-Ab(beta)
      (60-90), which is mostly alpha-helical, is more similar to the corresponding
      region of the class II MHC protein HLA-DR1 than to the class I MHC protein HLA
      A2. Arg-72 and Arg-80 lie on the same side of the helix and face away from the
      antigenic peptide binding groove. His-81, implicated in both superantigen and
      peptide binding, is located midway between the surface defined by Arg-72/Arg-80
      and residues that define the inside of the peptide binding groove, allowing for
      its participation in both types of binding.

PMID- 9175772
TI  - Structural and functional characterization of a second subfamily member of the
      calcium-modulated bovine rod outer segment membrane guanylate cyclase, ROS-GC2.
AB  - A native bovine calcium-modulated rod outer segment membrane guanylate cyclase
      (ROS-GC) has been cloned and reconstituted to show its linkage consistent to the
      process of phototransduction. In the present study, a second form of the membrane
      guanylate cyclase has been cloned from the bovine retina. This cyclase shares a
      high sequence identity with ROS-GC, is specifically expressed in the bovine
      retina, and, like ROS-GC, is modulated in low Ca2+ by a calmodulin-like Ca2+
      binding protein, termed GCAP2. For this reason, this cyclase has now been named
      ROS-GC2 and the previously described ROS-GC as ROS-GC1. The tail end of ROS-GC2
      contains a stretch of five amino acids, a structural feature unique to itself.
      These findings support the existence of a calcium-modulated subfamily of ROS-GC
      and indicate that ROS-GC2 embodies a five amino acid signature element at its
      tail end.

PMID- 9175773
TI  - Insulin inhibition of proteasome activity in intact cells.
AB  - Cellular homeostasis requires regulation of protein turnover. Protein degradation
      is an essential component of this process and is inhibited by insulin. The
      importance of cytosolic proteolysis in overall cellular protein degradation is
      increasingly apparent and an insulin effect on this system has been suggested but
      not proven. The present study shows that a membrane permeable substrate of the
      proteasome is degraded in HepG2 cells and that insulin inhibits its degradation
      both by isolated proteasomes and by intact cells. Inhibitors of the proteasome
      suppress degradation, and in the presence of these inhibitors insulin has no
      further effect. This is the first demonstration that insulin inhibition of
      cellular protein degradation is due to an effect on proteasomes.

PMID- 9175774
TI  - An alternative to phosphotyrosine-containing motifs for binding to an SH2 domain.
AB  - Shc is an important signalling protein whose overexpression leads to cell
      transformation in NIH 3T3 fibroblasts. Although the formation of Shc/Grb2
      complexes involving Shc tyrosine residue 317 is necessary to induce this
      transformation, the Shc proteins in these Shc-overexpressing cells are not
      substantially tyrosine-phosphorylated. This observation led to our hypothesis
      that the non-phosphorylated Tyr317-containing region of Shc might have specific
      affinity for the Grb2 protein. We show here that cell-permeable peptides
      encompassing the Shc Tyr317 region, 312FDD-PSYVNVQNL323, can bind to the SH2
      domain of Grb2 regardless of the state of tyrosine phosphorylation. When
      delivered into cells, both phosphorylated and non-phosphorylated Shc peptides
      inhibit growth factor-induced Shc/Grb2 protein-protein interaction. The non
      phosphorylated Shc peptides with single point mutations at Asp313, Asp314, or
      Tyr317 are inactive, suggesting that these residues play an important role in
      Grb2 protein recognition. Our findings represent the first paradigm of the
      specific interaction between an unphosphorylated tyrosine-containing region and
      an SH2 domain and have important implications for understanding the mechanism of
      cell transformation by Shc overexpression.

PMID- 9175775
TI  - Insulin stimulates p70 S6 kinase in the nucleus of cells.
AB  - Insulin action on both cytoplasmic and nuclear processes is dependent on
      activation of p70 S6 kinase (p70S6K). In CHO cells expressing human insulin
      receptors, Western blotting revealed the presence of p70S6K in the cell nucleus
      at a level of about 32% of that in the cytoplasm. Following insulin treatment,
      there was a retardation in mobility nuclear p70S6K in SDS-PAGE indicative of a
      change in phosphorylation of the enzyme, but no change in the amount of enzyme.
      Stimulation was maximal after 10 min of insulin treatment and decreased gradually
      at 30 min. There was also a rapid doubling of nuclear p70S6K activity in
      immunocomplex assays followed by a return to baseline by 30 min. Simultaneously,
      insulin stimulated cytoplasmic p70S6K by almost 10-fold at 10 min, and activity
      remained high up to 30 min. Tetradecanoylphorbol acetate (TPA) and fetal calf
      serum also stimulated nuclear p70S6K as judged by gel mobility shift. TPA also
      promoted a decrease in cytosolic p70S6K and an increase in nuclear enzyme
      suggestive of translocation of the enzyme. Rapamycin, a selective inhibitor of
      p70S6K, and the casein kinase II inhibitor DRB blocked insulin-stimulated nuclear
      and cytosolic p70S6K. Thus, nuclear p70S6K is regulated by insulin, serum and
      TPA. The insulin effect is downstream of rapamycin and DRB-sensitive targets and
      occurs without translocation of the enzyme.

PMID- 9175777
TI  - Ca2+ oscillations in plant cells: initiation by rapid elevation in cytosolic free
      Ca2+ levels.
AB  - Temporal increases in intracellular [Ca2+] are now recognized to be key triggers
      for a wide range of important physiological events in eukaryotic cells. In
      mammalian cells, signal-induced Ca2+-elevations have been found to be of a
      pulsatile nature and Ca2+ spikes display a high degree of spatiotemporal
      complexity. In plant cells a similar picture is beginning to emerge. To
      investigate the occurrence of pulsatile Ca2+ signals in plant cells we studied
      alterations of [Ca2+] in the tip region of pollen tubes from poppy (Papaver
      rhoeas). Time-Resolved Laser Scanning Confocal Microscopy of pollen tubes
      microinjected with the Dextran-linked Ca2+-indicator dyes Calcium Green or Indo-1
      revealed that highly regular Ca2+ oscillations occur in these cells. We further
      demonstrate that artificial elevation of cytosolic Ca2+ by photolysis of caged
      Ca2+ (Nitr-5) can trigger the onset of oscillations.

PMID- 9175776
TI  - Turnover studies of the neural cell adhesion molecule NCAM: degradation of NCAM
      in PC12 cells depends on the presence of NGF.
AB  - The neural cell adhesion molecule NCAM is a member of the immunoglobulin
      superfamily and involved in path finding and outgrowth of neurites in vitro. PC12
      cells express two major isoforms of NCAM (NCAM180 and NCAM140) and undergo
      neuronal differentiation, e.g., neurite formation, in response to NGF. Using this
      cell system, we determined the half-life time of both NCAM isoforms in the
      absence and presence of NGF. Half-life time of NCAM140 is similar in the presence
      and absence of NGF, whereas the half-life time of NCAM180 is increased in the
      presence of NGF. Furthermore, we quantified protein expression of both NCAM
      isoforms in the presence or absence of NGF and found a decrease of NCAM protein
      expression in course of neuronal differentiation.

PMID- 9175778
TI  - Introduction of DNA into rat liver with a hand-held gene gun: distribution of the
      expressed enzyme, [32P]DNA, and Ca2+ flux.
AB  - DNA-coated Au particles were accelerated by pressurized He gas to supersonic
      velocities for introduction of a gene into cells. Experimental and theoretical
      analyses both revealed a heterogeneous distribution of the particles per shot (1
      mg Au = 2.4 x 10(7) particles with 2 microg [32P] DNA = 2.5 x 10(11) moles). For
      introduction of genes into the liver of living rats, the best results were
      obtained with a newly developed hand-held gene delivery system. The beta
      galactosidase gene introduced into rat liver with Au particles by He at 250 psi
      was expressed (1.2 microunits/microg protein) in a limited area of the liver
      surface (8 x 8 mm, depth 0.5 mm). When the same gene gun was used on a monolayer
      of cultured COS7 cells (about 5 microm thick), cells were lost in the central
      area of heavy bombardment. Cell death caused by influx of Ca2+ was prevented by
      the use of the cytosol-type culture medium.

PMID- 9175779
TI  - Modulation of actin filament sliding by mutations of the SH2 cysteine in
      Dictyostelium myosin II.
AB  - The cysteine residue called SH2 in the skeletal myosin heavy chain is conserved
      among various species. Cys 678 in Dictyostelium myosin II is equivalent to SH2 in
      skeletal myosin. Using the Dictyostelium myosin II heavy chain gene, SH2 was
      mutated to Gly, Ala, Ser, or Thr. These mutant myosins were expressed in
      Dictyostelium myosin-null cells. To investigate how these mutations affect the
      motor functions of myosin, we examined the phenotypes of the transformed cells.
      We also purified the mutant myosins, and characterized them by measuring the
      actin-activated MgATPase activity, sliding velocity of actin filaments and force
      level. All of these mutant myosins complemented the myosin-specific defects of
      the myosin-null cells. Consistent with these observed phenotypes, all of the
      purified mutant myosins retained similar actin-activated MgATPase activities and
      force levels to those of the wild-type myosin (WT). However, the sliding
      velocities of actin filaments were significantly different (WT > or = Ser > Ala
      >> Thr > Gly). In particular, the Gly and Thr mutants exhibited a striking
      decrease in velocity, while the Ser mutant exhibited velocity comparable to that
      of the wild-type myosin. Thus, mutations of SH2 resulted in uncoupling of ATP
      hydrolysis and the sliding.

PMID- 9175780
TI  - Growth retardation, testicular stimulation, and increased melatonin synthesis by
      weak magnetic fields (50 Hz) in Djungarian hamsters, Phodopus sungorus.
AB  - Male Djungarian hamsters (Phodopus sungorus; 45 animals per group) were either
      sham-exposed or exposed to a sinusoidal magnetic field for 56 days (Experiment 1:
      50 Hz, 450 microTesla peak; max. dB/dt = 140 mTesla s(-1); 24 hrs day(-1)).
      Except for day 7, no effects were observed with respect to body weights during
      exposure. However, testicular cell numbers were significantly increased by
      exposure (tetraploid (4C): p=0.022; diploid (2C): p=0.039). Rectangular magnetic
      fields (Experiment 2: 360 microTesla; max. dB/dt = 2.5 Tesla s(-1)) caused a
      significant (p<0.001) but transient suppressing effect on body weights.
      Significant increases were also observed in testicular cell numbers (4C: p=0.034;
      haploid (1C): p=0.014) and in serum melatonin (p=0.001). It is concluded that
      weak magnetic fields may affect reproductive and physiological functions in the
      mammalian species tested and that the degree of these effects depends upon the
      fields' gradients.

PMID- 9175781
TI  - The glycoproteins that occur in the colloids of senescent porcine pituitary
      glands are clusterin and glycosylated albumin fragments.
AB  - Periodic acid-Schiff-positive colloids occur in the pituitary glands of many
      vertebrates. These colloids are surrounded by folliculo-stellate (FS) cells and
      increase dramatically in number and size with age. The characterization of these
      colloidal substances is necessary for the establishment of FS cell function. In a
      previous study we showed that these colloids in the senescent pituitary contain a
      number of glycoproteins; however, the characterization of these glycoproteins has
      not yet been carried out. To characterize the pituitary colloid, we purified the
      colloids by centrifugation and Percoll gradient. The isolated colloids were
      unable to be solubilized in a regular buffer since they were very dense. However,
      solubilization was accomplished in sodium dodecyl sulfate (SDS) lysis buffer
      following treatment with exoglycosidase. Analysis using SDS-polyacrylamide gel
      electrophoresis showed that the porcine pituitary colloids contain four proteins,
      CP26, CP40, CP48 and CP60, whose estimated molecular weights were 26 kD, 36-43
      kD, 48 kD, and 60 kD, respectively. Staining with concanavalin A (ConA) showed
      that both CP26 and CP40 were glycoproteins. Moreover, N-terminal amino acid
      sequencing and Western blot analysis revealed CP26, CP48 and CP60 to be porcine
      albumin while CP40, the major protein in the colloids, proved to be clusterin.
      Therefore we report here that the glycoproteins that occur in senescent porcine
      pituitary colloids are of two types, namely, albumin fragments and clusterin.

PMID- 9175782
TI  - Protein insolubility and late-stage morphogenesis in long-term postconfluent
      cultures of MDCK epithelial cells.
AB  - Epithelial morphogenesis in vitro has been studied in cultures soon after cell
      cell contact at confluency when several actin-associated proteins (fodrin,
      adherens junction molecules E-cadherin and catenins) localize to specific
      subcellular domains and become resistant to extraction with non-ionic detergents.
      Here we demonstrate that early confluency is followed by a long postconfluent
      period of several weeks during which these proteins and actin itself become
      progressively enriched in the detergent-resistant fraction of MDCK epithelial
      cells. Cultures from another tissue (human retinal pigment epithelium) which
      produces weakly epithelialized monolayers in culture do not exhibit similar late
      stage increases in protein insolubility. After confluency some cells in MDCK
      cultures undergo additional morphogenetic changes giving rise to cord-like
      structures, and the MDCK adherens junction becomes more stable to disrupting
      agents. These results indicate that in vitro morphogenesis is not restricted to
      early confluency in MDCK cells but rather molecular stabilization and dynamic
      changes in cell shape occur over a protracted postconfluent interval.

PMID- 9175783
TI  - Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet
      lysosomal cathepsin A-like enzyme.
AB  - Lactacystin, the most specific inhibitor of the proteasome, strongly inhibited at
      pH 5.5 the activity of human platelet lysosomal cathepsin A-like enzyme. At a
      concentration as low as 1-5 microM it almost completely decreased the hydrolysis
      rate of cathepsin A specific substrates: Cbz-Phe-Ala and FA-Phe-Phe. This
      inhibition was probably due to the lactacystin intermediate beta-lactone formed
      during 10 min hydrolysis at pH 8.0 since nonhydrolyzed inhibitor did not affect
      cathepsin A activity. Basing on similarities in the inhibitor sensitivity, pH
      optimum, and substrate preferences it is suggested that the cathepsin A-like
      activity may be involved in chymotrypsin-like activity of the proteasome.

PMID- 9175784
TI  - Evidence for distinct behaviour of phosphatidylcholine and sphingomyelin at the
      low density lipoprotein surface.
AB  - This study demonstrates that the use of high field 1H NMR spectroscopy permits
      individual detection of phosphatidylcholine and sphingomyelin molecules at the
      surface of native low density lipoprotein (LDL) particles. Distinct behaviour was
      observed for the choline head group -N(CH3)3 resonances of these different
      phospholipids revealing preferential immobilisation for phosphatidylcholine. This
      suggests the existence of reversible and irreversible phosphatidylcholine
      apolipoprotein B interactions and is consistent with microdomain formation at the
      surface monolayer of LDL. The novel resonance assignment and results show that 1H
      NMR can provide efficient and practical means for future studies on the structure
      and dynamics at the LDL surface.

PMID- 9175785
TI  - Ceramide inhibits nitric oxide production in alveolar macrophages of endotoxin
      and ethanol plus endotoxin-treated rats.
AB  - The effect of ceramide on nitric oxide (NO) formation was studied in rat alveolar
      macrophages (AMs). Rats were infused with ethanol (EtOH) for 3 h, or the EtOH
      infusion was combined with i.v. injection of endotoxin (ET) 90 min into the
      infusion. Controls were infused with saline. Alveolar macrophages were obtained
      by bronchoalveolar lavage and were cultured for 20 h in the presence and absence
      of ET, interferon-gamma (IFN), C6 ceramide (N-hexanoylsphingosine), and C2
      dihydroceramide. Nitric oxide formation was assessed by measurement of nitrites
      in the medium. C6 ceramide significantly suppressed NO formation in response to
      in vitro addition of ET, but not IFN. C2 dihydroceramide caused no inhibition.
      The ceramide effect appears to be not only stimulus specific, but also specific
      to AMs, since NO formation by Kupffer cells and liver infiltrated neutrophils was
      not affected. The results suggest involvement of the sphingomyelin cycle in ET
      stimulated NO formation in rat AMs.

PMID- 9175786
TI  - Transcriptional activation of human LIM-HOX gene hLH-2 in chronic myelogenous
      leukemia is due to a cis-acting effect of Bcr-Abl.
AB  - DNA methylation plays an important role in gene regulation. A human LIM-HOX gene,
      namely hLH-2, was highly expressed in chronic myelogenous leukemia (CML) and
      located on chromosome 9q33-34.1, in the same region as the reciprocal
      translocation that creates the Bcr-Abl chimera of Philadelphia chromosome [Wu et
      al. (1996) Oncogene 12, 1205]. To elucidate the mechanism of hLH-2
      transcriptional activation, we studied the methylation status of hLH-2 in normal
      bone marrow and CML cells. When blots containing genomic DNA digested with Hpa II
      or Msp I were hybridized with full-length cDNA probe, it was discovered that hLH
      2 was methylated in normal bone marrow cells in which hLH-2 was not expressed; in
      contrast, both alleles of hLH-2 locus in CML cells were heavily hypomethylated.
      Furthermore, using the sensitive RT-PCR technique, we examined the expression of
      LH-2 in mouse x human hybrids and a wide array of mouse cell lines containing Abl
      or Bcr-Abl and failed to identify a consistent expression pattern in the cell
      lines tested. These results suggest that the transcriptional activation of hLH-2
      in CML is likely due to a cis-acting effect, but not a trans-acting effect of the
      Bcr-Abl fusion protein. Because hypomethylated genes generally are transcribed
      more efficiently than hypermethylated genes, the high level of hLH-2 mRNA in CML
      cells probably is a consequence of the low level of methylation of the gene in
      the leukemic cells.

PMID- 9175787
TI  - Identification of signalling components in tyrosine kinase cascades using
      phosphopeptide affinity chromatography.
AB  - Various methods are now available to identify the molecular partners of the
      component of a signal transduction pathway. Some interactions, however, can be
      technically difficult to detect because they depend upon transient tyrosine
      phosphorylation. Here, we present a simple affinity chromatography approach based
      on synthetic phosphopeptides to purify potential partners of phosphotyrosine
      containing proteins. With this approach, we confirm the previously characterized
      interaction between Grb2 and the EGF receptor, and we identify novel partners of
      the IGF-1 receptor and of the JAK proteins. Methenyltetrahydrofolate synthetase
      (MTHFS) was identified as a potential mediator of IGF-1R dependent
      transformation. P85alpha, the regulatory subunit of PI3 kinase, was identified as
      one of four proteins recruited by a phosphopeptide mimicking a motif conserved in
      all JAK family members.

PMID- 9175788
TI  - Identification of a chick homologue of Fringe and C-Fringe 1: involvement in the
      neurogenesis and the somitogenesis.
AB  - In Drosophila, Serrate plays an important role to the wing margin formation. A
      putative secretory protein, Fringe, is indispensable for the wing margin
      formation inducing Serrate and other genes. Recently, Xenopus homologues of
      Fringe were identified and one of them, lunatic Fringe (X-lFng), was demonstrated
      to be involved in mesoderm induction. We have identified two chick Fringe
      homologous genes by reverse transcription-polymerase chain reaction and cDNA
      library screening. One of them, C-Fringe 1, showed sequence similarity to X-lFng.
      In situ hybridization study of C-Fringe 1 has demonstrated its expression in the
      developing nervous system and in the presomitic mesoderm. The hindbrain and
      spinal cord showed the distinct stripe pattern expression which was complementary
      to that of C-Serrate, indicating the correlation between them in vertebrate.

PMID- 9175789
TI  - Active nuclear transport of chicken lipovitellin-2.
AB  - Chicken lipovitellin-2 is a small, approximately 30 kDa yolk protein, derived
      from the intracellular breakdown of the precursor protein vitellogenin. In
      principle, lipovitellin-2 is small enough to directly diffuse into the nucleus.
      Our results, however, demonstrate that its nuclear transport is an active process
      which can be inhibited by wheat germ agglutinin, chilling, and energy depletion.
      The N-terminal sequence analysis identifies chicken lipovitellin-2 beginning at
      Ala1544 in the C-terminal region of vitellogenin yielding of protein of 30,982
      Da.

PMID- 9175790
TI  - Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in
      type A syndrome of extreme insulin resistance.
AB  - To elucidate genetic determinants of insulin resistance, we investigated insulin
      receptor (IR) and insulin receptor substrate-1 (IRS-1) genes, in vitro IR
      function and in vivo insulin sensitivity in a family with Type A syndrome. Two
      missense IR mutations (Asp59Gly and Leu62Pro) found in the proband, resulted in
      reduction by 90% of insulin binding to erythrocytes, decreased receptor
      autophosphorylation and a dramatic reduction of insulin sensitivity. The proband
      and mother were heterozygote for Gly972Arg IRS-1 variant. Asp59Gly mutation, also
      carried by proband's brother with no consequence on insulin sensitivity, was
      inherited from the mother who is diabetic and insulin resistant and Leu62Pro was
      from the father. We conclude that severity of insulin resistance in the proband
      may be explained by the genetic condition of compound heterozygote for IR
      mutations while severe insulin resistance in the mother raises the possibility
      that other genetic factors, like IRS-1 polymorphisms, may contribute to the
      phenotypic expression of IR mutations.

PMID- 9175791
TI  - Controlled gene expression with a reverse tetracycline-regulated retroviral
      vector (RTRV) system.
AB  - A retroviral vector was constructed with an autoregulatory cassette to allow
      expression of the gene of interest in response to oral administration of
      doxycycline (Dox) in vivo. The cassette contains all the components of the
      reverse tetracycline-regulated (rtTA) system, a drug selectable marker with the
      internal ribosome entry site and the gene of interest (GFP). FACS analyses showed
      an induction of GFP-fluorescence of two orders of magnitude in retrovirus
      infected 208F cells dependent on the amount of Dox in the medium. Furthermore,
      oral administration of Dox resulted in GFP expression in transplanted 208F cells
      in the peritoneal cavity of nude mice. Thus this reverse tetracycline-regulated
      retroviral vector (RTRV) system simplifies the delivery of controllable genes to
      cultured and implanted cells. It is hoped that this approach may pave the way to
      controlled gene expression during a particular window of time in gene therapy
      applications.

PMID- 9175792
TI  - Spin trapping study of antioxidant properties of neopterin and 7,8
      dihydroneopterin.
AB  - Previously, it has been shown that pteridine derivatives are capable of
      modulating the action of free radicals and both prooxidant and antioxidant
      properties have been described. However, the mechanism of manifestation of these
      properties is still unclear. We studied the radical scavenging properties of 7,8
      dihydroneopterin and neopterin using the spin trap 5,5-dimethyl-1-pyrroline-1
      oxide (DMPO). It was found that dihydroneopterin acts generally as a radical
      scavenger. In the presence of dihydroneopterin the ESR signal was reduced by 30
      to 90% compared to the control signal. The rate constants for the reactions of
      7,8-dihydroneopterin with superoxide (10(3) M(-1) s(-1)) and peroxyl radicals
      (10(7) M(-1) s(-1)) were determined. Neopterin in contrast showed no reduction of
      the ESR signal except with superoxide radicals produced by xanthine oxidase.
      However, this effect was shown to be due to an inhibition of enzyme rather than
      to radical scavenging. Our results provide a basis for understanding previous
      observations of radical scavenger activity of 7,8-dihydroneopterin.

PMID- 9175793
TI  - Molecular analysis of the O alleles at the blood group ABO locus in populations
      of different ethnic origin reveals novel crossing-over events and point
      mutations.
AB  - The blood group ABO genotypes of 138 group O individuals with three different
      ethnic origins in Brazil were determined, including Whites, Blacks and
      Amerindians. Several previously undescribed O alleles were found, predominantly
      in the Black group, in which about a third of the samples did not conform to
      previously known O allele structures. It has been well documented for the first
      time that some new alleles can arise from crossing-over events between known
      alleles in the ABO system. This was made possible by both restriction
      endonuclease analysis and direct sequencing of exons 3-7 in the ABO gene. The
      anticipated relatively high frequency of some of these new alleles in certain
      populations, necessitates great care when interpreting results from existing
      genotype screening methods.

PMID- 9175794
TI  - Lymphocytes bursting induced by heparin, dextran sulfate and other polyanions.
AB  - We found that high molecular polyanions (PAs) such as dextran sulfate and heparin
      burst some damaged or dead lymphocytes in lymphocyte suspension isolated from
      living bodies, and clarified morphologically the mechanism involved in this. PAs
      passed through damaged cell membranes and reached the chromatin in the nucleus.
      Electron micrographs suggested that they then extracted histones from the
      chromatin and formed complexes with them, and that freed DNA formed a gel binding
      with the complexes in the nucleus, and the nucleus became swollen and burst due
      to the gel swelling pressure. To support this conjecture, the nuclei of
      lymphocytes were stained with propidium iodide and exposed to light to stabilize
      them. The stabilized nuclei were not swollen after the addition of PAs and the
      lymphocytes did not burst. The lymphocyte bursting effect of PAs was attributed
      to their negative charges which could not destroy intact cells. At this point,
      PAs are different from sodium dodecyl sulfate which destroys intact cells
      completely.

PMID- 9175795
TI  - Identification and characterization of the SMT3 cDNA and gene from nematode
      Caenorhabditis elegans.
AB  - SMT3 gene from nematode, Caenorhabditis elegans, was identified and sequenced.
      The nematode SMT3 gene codes for a homolog to the yeast SMT3, suppressor of MIF2
      mutation in a centromere protein gene. Further, nematode SMT3 cDNA was amplified
      by polymerase chain reaction from a cDNA library and its nucleotide sequence
      determined. A comparison of the SMT3 genomic and cDNA sequences established that
      the protein-encoding sequence is interrupted by two introns of 56 and 50 bp at
      codon Nos. 22-23 and 56, respectively. The sequence of 91 amino acids deduced
      from the nematode SMT3 nucleotide sequence exhibited 42 and 47% identity to the
      yeast and human SMT3 protein sequences, respectively. The evolutionary
      relationships of SMT3 proteins from human, nematode, Arabidopsis, rice, and yeast
      were analyzed.

PMID- 9175796
TI  - Localization of cryptic tolerogenic epitopes in the alpha1-helical region of the
      RT1.Au alloantigen.
AB  - BACKGROUND: Transplantation tolerance is induced by perioperative administration
      of host class I major histocompatibility complex proteins bearing donor-type
      amino acid (a.a.) epitopes substituted for native residues. Herein we demonstrate
      that two cryptic tolerogenic a.a. epitopes are localized in the alpha1-helical
      region of the rat RT1.Au class I major histocompatibility complex alloantigen.
      METHODS: Three allochimeric proteins were produced by superimposing the
      nucleotides encoding donor-type RT1.Au a.a. onto the host RT1.Aa backbone using
      the polymerase chain reaction-based method of gene splicing with overlap
      extension. We substituted nucleotide sequences encoding all nine (Arg62, Glu63,
      Gln65, Gly66, Gly69, His70, Val73, Asn74, and Asn77; alpha1h u62-77-RT1.Aa), the
      first four (Arg62, Glu63, Gln65, and Gly69; alpha1h u62-69-RT1.Aa), or the last
      four (His70, Val73, Asn74, and Asn77; alpha1h u70-77-RT1.Aa) alpha1-helical
      RT1.Au polymorphic a.a. in RT1.Aa cDNA. A baculovirus/Spodoptera frugiperda (Sf9)
      expression system was harnessed for production of the proteins. RESULTS:
      Untreated ACI (RT1a) rats reject Wistar-Furth (WF; RT1u) heart allografts at a
      mean survival time of 8.9+/-1.0 days. A single portal vein injection of 10 microg
      of alpha1h u62-77-RT1.Aa protein had no effect on the survival of WF heart
      allografts (10.5+/-0.6 days) in ACI hosts. Interestingly, portal vein
      administration of 10 microg of alpha1h u70-77-RT1.Aa induced transplantation
      tolerance toward WF grafts in four of six untreated ACI recipients (>100 days;
      P<0.01). In contrast, 10 microg of alpha1h u62-69-RT1.Aa only prolonged the
      survival of WF heart allografts in ACI hosts (14.0+/-0.8 days; P<0.01). However,
      when combined with a 7-day course of cyclosporine (4.0 mg/kg; oral gavage),
      alpha1h u62-69-RT1.Aa induced tolerance toward WF allografts in five of seven ACI
      recipients (>170 days; P<0.01). Long-term survival of WF grafts was not achieved
      when a 7-day course of cyclosporine was administered alone (14.3+/-3.0 days) or
      with 10 microg of alpha1h u62-77-RT1.Aa (14.6+/-0.6 days; NS). CONCLUSIONS: These
      findings suggest that the use of allochimeric proteins may provide a novel
      approach to the induction of tolerance.

PMID- 9175797
TI  - Inhaled nitric oxide attenuates reperfusion injury in non-heartbeating-donor lung
      transplantation. Paris-Sud University Lung Transplantation Group.
AB  - BACKGROUND: Non-heartbeating-donor (NHBD) lung transplantation could help reduce
      the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a
      pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric
      oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung
      transplantation. METHODS: The effect of inhaled NO on PMNs was studied by
      measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion
      of recipient circulating PMNs to cultured pulmonary artery endothelial cells
      (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9
      each). In the NO group, cadavers and recipients were ventilated with oxygen and
      30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2
      hr of cold ischemia, left allotransplantation was performed. The right pulmonary
      artery was ligated, and hemodynamic and gas exchange data were recorded hourly
      for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium
      ionophore-stimulated PAECs was measured before and after reperfusion, and lung
      PMN sequestration was determined after death. RESULTS: NO-treated animals
      exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved
      oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was
      inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung
      PMN sequestration was reduced by NO (P<0.05). CONCLUSIONS: Inhaled NO attenuates
      I-R injury after NHBD lung transplantation. This is likely due to the prevention
      of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral
      blood PMN adhesion to endothelium, which results in reduced sequestration and
      tissue injury.

PMID- 9175798
TI  - Bone marrow transplantation in newborn rats with mucopolysaccharidosis type VI:
      biochemical, pathological, and clinical findings.
AB  - BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) is the lysosomal storage
      disorder caused by the deficient activity of arylsulfatase B (ASB). In this
      study, we evaluated bone marrow transplantation (BMT) for the treatment of MPS VI
      and the effects of irradiation on the survival and engraftment of bone marrow
      transplanted neonatal rats. METHODS: One- to 2-day-old MPS VI rats were injected
      with normal bone marrow after irradiation with 200, 400, or 800 cGy. Ninety
      percent of the animals receiving a single dose of 200 cGy (n=30) survived the
      procedure, whereas irradiation with 400 cGy (n=23) or 800 cGy (n=12) resulted in
      significant mortality (78% and 100%, respectively). Engraftment was monitored by
      determining ASB activities in peripheral white blood cells and by Y chromosome in
      situ hybridization analysis. Fifty-two percent of the animals from the 200-cGy
      group engrafted for up to 8 months after BMT; among the five animals that
      survived the 400-cGy dose, all engrafted. In comparison, only 20% of
      nonirradiated animals engrafted at low levels. Of the 24 engrafted animals that
      were monitored for 8 months after BMT, clinical and/or radiographic improvements
      were noted in only one (BMT animal 3). Enzymatic analysis revealed that the ASB
      activities in the reticuloendothelial organs of this animal, as well as two other
      engrafted but clinically unimproved animals (BMT animals 1 and 2), were normal or
      near normal; correspondingly, the glycosaminoglycan levels in these organs were
      significantly reduced. Consistent with the clinical and biochemical observations,
      light and electron microscopic findings were more improved in BMT animal 3 as
      compared with BMT animals 1 and 2, although a reduction of storage was evident in
      each of these transplant recipients, particularly in the trachea and aorta, two
      tissues that are characteristic sites of pathology in human patients.
      CONCLUSIONS: These results indicate that BMT in newborn MPS VI patients may
      prevent many of the pathological and clinical findings in this disorder, but is
      likely to have very limited and unpredictable effects on the skeletal
      abnormalities.

PMID- 9175799
TI  - Permanent and specific transplantation tolerance induced by a nonmyeloablative
      treatment to a wide variety of allogeneic tissues: I. Induction of tolerance by a
      short course of total lymphoid irradiation and selective elimination of the donor
      specific host lymphocytes.
AB  - The long-term success of organ transplantation is limited by complications
      resulting from consistent nonspecific immunosuppression. Induction of stable,
      donor-specific tolerance remains the main goal of transplantation immunology. In
      this article, a new, nonmyeloablative method is described for induction of
      transplantation tolerance to fully mismatched bone marrow cells (BMC), bone
      marrow stromal precursors, heart muscle, and skin allografts. The method is based
      on pretransplant conditioning with no postgraft immunosuppression, and consists
      of a short course (six daily fractions of 200 cGy) of total lymphoid irradiation
      (sTLI), followed by selective elimination of donor-specific alloreactive cells of
      the host escaping low-dose sTLI. Donor-specific alloreactive cells were activated
      by intravenous inoculation with a high dose of donor BMC (3 x 10(7) cells) 1 day
      after sTLI, and eliminated by a single intraperitoneal dose (200 mg/kg) of
      cyclophosphamide given 1 day after cell transfer. Infusion of a low number of T
      cell-depleted BMC (3 x 10(6) cells) after tolerogenic preconditioning converted
      recipients to stable mixed chimeras free of graft-versus-host disease. The same
      treatment provided long-lasting acceptance of heterotopically transplanted
      allografts of the heart muscle and of the stromal precursors to the hematopoietic
      microenvironment. This treatment also led to acceptance and life-long survival of
      full-thickness donor skin allografts. However, skin allografts survived only in
      mice that received donor T cell-depleted BMC after cyclophosphamide and had 20
      50% donor cells in the blood. Our results suggest that after sTLI, additional
      selective clonal deletion of residual host cells induces a state of long-lasting
      specific tolerance to a wide variety of donor-derived tissues.

PMID- 9175800
TI  - The asystolic donor syndrome: transaminitis and thrombocytopenia after non
      heartbeating renal transplantation.
AB  - BACKGROUND: The use of kidneys from non-heartbeating donors (NHB) remains
      controversial. An increased incidence of delayed primary function and primary
      nonfunction is common. We report a characteristic syndrome of transaminitis and
      thrombocytopenia after NHB renal transplantation, which may be predictive of
      graft outcome. METHODS: Two case histories are presented, followed by a
      retrospective analysis of 38 NHB renal grafts performed at Guy's Hospital from
      1988 to 1994. Changes in alanine aminotransferase (ALT) and platelet count were
      compared between recipients of kidneys from NHB and heartbeating donors (HB). To
      control for possible effects of antilymphocyte globulin (ALG), two matched
      control groups receiving HB kidneys with (n=32) and without (n=32) ALG were also
      compared. RESULTS: ALT was elevated in 32 of 38 (84%) of NHB recipients and 19 of
      64 (30%) controls (P<0.001). Mean peak ALT was 172+/-20 U/L in NHB and 42+/-6 U/L
      in HB kidneys (P<0.001). Use of ALG did not influence mean peak ALT. Elevated ALT
      predicted impaired graft function (P<0.02) and was associated with an increased
      length of delayed primary function (P<0.001) and risk of transplant nephrectomy
      (P<0.05). Thrombocytopenia (<100 x 10(9) cells/L) occurred in 18 of 38 (47%) NHB
      recipients and in 20 of 64 (31%) controls (P<0.05). Mean nadir platelet count (x
      10(9) cells/L) was 113+/-10 in NHB, 128+/-9 in HB with ALG, and 164+/-9 in HB
      without ALG (both P<0.05 vs. NHB). Patients who underwent graft nephrectomy (n=9)
      had a disproportionate fall in platelet count (mean nadir, 80+/-11 x 10(9)
      cells/L; P<0.05). CONCLUSIONS: Transaminitis and thrombocytopenia occur commonly
      after NHB kidney transplantation and are predictive of graft outcome. Recognition
      of these changes may assist the early management of NHB renal recipients, and
      also reduce investigation of "anomalous" results in this setting.

PMID- 9175801
TI  - Outcome of en bloc and single kidney transplantation from very young cadaveric
      donors.
AB  - BACKGROUND: The optimal use of very young cadaveric kidneys (from donors less
      than 4 years old) remains controversial. High rates of technical complications
      and poor functional results compared with adult donor kidneys have been reported.
      The use of en bloc transplantation to overcome these problems has been advocated,
      although en bloc transplantation halves the number of potential transplants from
      very young donors. METHODS: We studied the technical and functional results of 91
      transplants from very young donors performed at our institution between 1984 and
      1995. This included 59 single and 22 en bloc procedures involving first
      transplants and 7 single and 3 en bloc procedures involving retransplantation.
      Individual surgeon preference dictated the use of either the single or en bloc
      technique. Kidneys smaller than 6 cm tended to be transplanted en bloc, and
      lighter patients were generally given preference for receiving pediatric kidneys.
      Patients received sequential cyclosporine-based quadruple immunosuppression.
      RESULTS: En bloc kidneys had a 1-year and 5-year graft survival of 82% and 70%,
      respectively. Single kidneys had a 1-year and 5-year graft survival of 64% and
      40%. Kidneys that avoided acute rejection episodes and that were transplanted
      into heavier or male recipients had better long-term survival. Kidneys from
      donors less than 2 years old did poorly whether transplanted en bloc or singly.
      Better HLA matching improved short-term, but not long-term, graft survival,
      whereas cold ischemic time did not have statistically significant association
      with differences in graft survival. Eleven percent of the transplants had
      ureteral leaks, but only one kidney was lost. Ten transplants had vascular
      complications leading to graft loss, whereas two episodes of arterial stenosis
      were successfully treated with percutaneous angioplasty. CONCLUSIONS: En bloc
      transplantation optimizes the outcome of transplantation with very young kidneys.
      We recommend induction therapy and cyclosporine immunosuppression with
      cyclosporine levels similar to adult target levels to minimize rejection episodes
      and, thus, improve outcome. These kidneys should be distributed nationally,
      because better HLA matching is associated with improved short-term graft
      survival. Our high ureteral leak rate indicates that alternatives to unstented
      ureteroneocystostomy should be considered.

PMID- 9175802
TI  - Enhanced (cytomegalovirus) viral replication associated with septic bacterial
      complications in liver transplant recipients.
AB  - BACKGROUND: Complications of the biliary anastomosis are the principal cause of
      clinically serious bacterial sepsis in liver transplant recipients. Reported
      series suggest an association of bacterial and fungal infection with
      cytomegalovirus (CMV) infection, although the mechanism of this association is
      unclear. METHODS: We examined the association of serious bacterial sepsis with
      CMV replication in a cohort of 106 consecutive liver transplant recipients.
      Sequentially collected buffy coats were examined with a polymerase chain reaction
      (PCR) assay that has been shown to have good predictive value for the development
      of CMV infection. For selected patients, CMV-specific IgM response and serum
      tumor necrosis factor-alpha (TNF-alpha) were also measured. RESULTS: Ten of 13
      patients with serious bacterial sepsis developed buffy coat PCR positivity,
      compared with 26 of 93 patients without bacterial sepsis (chi-square, P<0.001).
      Ten of 10 septic recipients with a seropositive liver donor developed PCR
      positivity. For 9 of 10 recipients, bacterial sepsis developed before PCR
      positivity. Bacterial sepsis was associated with high serum levels of TNF-alpha.
      Immune response to CMV (reflected by the appearance CMV-specific IgM) was
      apparently affected by bacterial sepsis, and IgM response was not observed for
      the three septic patients who died during the study period. CONCLUSIONS: We
      conclude that CMV replication is encouraged by serious bacterial sepsis.
      Replication may be promoted by high antecedent levels of TNF-alpha, and/or by
      poor immune response to CMV in the context of serious bacterial infection.

PMID- 9175803
TI  - Pretransplant famciclovir as prophylaxis for hepatitis B virus recurrence after
      liver transplantation.
AB  - Liver transplantation in patients with detectable hepatitis B virus (HBV) DNA is
      associated with a high rate of HBV recurrence and detectable HBV DNA is often
      considered a contraindication for liver transplantation. Famciclovir, an oral
      form of the purine nucleoside penciclovir, has been shown to inhibit HBV
      replication. This pilot study was conducted to determine whether a 6-month course
      of famciclovir, administered before transplantation, was effective in inhibiting
      HBV replication in patients with end-stage liver disease caused by HBV and
      detectable HBV DNA and to assess the posttransplant clinical and virologic
      outcome of patients becoming HBV DNA negative with famciclovir prior to
      transplantation. All eight patients enrolled were hepatitis B surface antigen
      (HBsAg) positive; their HBV DNA levels at baseline ranged from 4.3 to 25,321
      pg/ml (mean 3,661 pg/ml). Six of the eight patients were also seropositive for
      HBeAg. An initial decline in HBV DNA titers occurred in all patients; however,
      only 25% (two of eight) of the patients became HBV DNA negative before
      transplantation and underwent liver transplantation. Seroconversion to hepatitis
      B surface antibody (HBsAb) (and HBeAb in HBeAg-positive patient) was demonstrated
      at the conclusion of famciclovir in the transplanted patients. Both patients
      remain HBV DNA negative at nearly 2 years of follow-up after transplantation. HBV
      DNA remained detectable in 63% (five of eight) of the patients. The mean HBV DNA
      level for patients who became HBV DNA negative was 5.1 pg/ml versus 424 pg/ml in
      nonresponders. Adverse effects attributable to famciclovir were not observed in
      any of the patients. Future studies should assess the predictors of response to
      famciclovir so that patients likely to achieve good virologic outcome can be
      targeted for such a therapy.

PMID- 9175804
TI  - Relationship between hepatitis C genotype and severity of recurrent hepatitis C
      after liver transplantation.
AB  - BACKGROUND: Recurrence of hepatitis C virus (HCV) infection after liver
      transplantation is universal, but the relationship between hepatitis C genotype
      and posttransplant outcome has been controversial. The aim of this study was to
      assess the relationship between hepatitis C genotype on posttransplant frequency
      of recurrent hepatitis, histologic severity of recurrence, and progression to
      cirrhosis. METHODS: We studied 42 HCV RNA positive patients who received
      transplants between 1985 and 1994. Sera were tested for HCV RNA and protocol
      liver biopsies were in obtained the posttransplant period. Biopsies were scored
      according to the histologic activity index (HAI) and staged in a blinded fashion.
      RESULTS: The distribution of hepatitis C genotypes distribution was as follows:
      1a, 19 (45%); 1b, 17 (40%); 2b, 3 (7%); and 1 each of 2a, 3a, and 4a. There was
      histologic evidence of hepatitis in 38 of 42 (90.4%) of patients. Hepatitis C was
      mild, moderate, or severe (HAI>3) in 38% of grafts and minimal (HAI 0-3) in 62%.
      Overall HAI scores and histologic stage were higher in the genotype 1b group. Six
      of 17 (35%) genotype 1b patients had cirrhosis compared with 2 of 25 (8%) in the
      non-1b genotype group. CONCLUSIONS: (1) Histologic evidence of recurrent
      hepatitis C is seen in 90% of liver allografts; (2) Histologic hepatitis C recurs
      with similar frequency in genotype 1b and non-1b recipients; (3) Genotype 1b is
      associated with more severe histologic disease recurrence than non-1b genotypes;
      (4) Genotype 1b appears to be associated with a higher degree of posttransplant
      fibrosis and cirrhosis than non-1b genotypes.

PMID- 9175805
TI  - Decreased patient analgesic requirements after liver transplantation and
      associated neuropeptide levels.
AB  - BACKGROUND: Decreased morphine requirements have been reported after liver
      transplantation when compared with other types of major abdominal surgery. The
      aim of this study was to examine plasma concentrations of three neuropeptides
      involved in pain modulation-metenkephalin (ME), beta-endorphin (BE), and
      substance P (SP)-in patients undergoing orthotopic liver transplantation (OLT)
      and in control patients undergoing other liver operations. We then compared the
      postoperative analgesic requirements in these two groups of patients. METHODS:
      Plasma levels of ME, BE, and SP were measured by radioimmunoassay at preincision,
      preemergence, and for 3 days after operation in 13 patients undergoing OLT and in
      10 control patients. Patient-controlled analgesia morphine delivery was recorded
      for all patients postoperatively, and plasma morphine, its metabolites, and
      patient pain and sedation scores were also measured. RESULTS: ME levels were
      elevated in all OLT patient samples when compared with control patient samples.
      BE levels were not significantly different at any time. SP levels were
      significantly decreased only in preincision and preemergence OLT patient samples.
      Total patient-controlled analgesia morphine delivered during the first 3
      postoperative days was significantly less in OLT patients (70+/-8 mg) than in
      control patients (101+/-12 mg). Plasma morphine, morphine-3-glucuronide, and
      morphine-6-glucuronide levels were decreased in OLT patients, however,
      statistical significance was seen only in the morphine-6-glucuronide results.
      CONCLUSIONS: We have shown that postoperative analgesic requirements are
      decreased in OLT patients, and we suggest that associated increased peripheral ME
      levels may be contributing to this decreased requirement. Based on our results,
      circulating BE and SP are less significant factors affecting postoperative
      analgesic requirements.

PMID- 9175806
TI  - Predictive value of cytomegalovirus DNA detection by polymerase chain reaction in
      blood and bronchoalveolar lavage in lung transplant patients.
AB  - BACKGROUND: Despite promising results, the efficacy of polymerase chain reaction
      (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted
      patients is still controversial. METHODS: A prospective study of CMV detection,
      with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage
      (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months
      (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp
      fragment in the Us region and a 290-bp fragment in the immediate early region of
      the viral genome. RESULTS: When comparing PCR to viral culture, the sensitivity
      and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and
      100% and 75% in BAL (n=104). The positive and negative predictive values of PCR
      for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67%
      and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment:
      when PCR was still positive either in blood or BAL, CMV infection relapsed within
      35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days
      (P=0.01). CONCLUSIONS: Negative CMV detection by PCR strongly advocates against a
      forthcoming CMV infection. PCR assay seems to be a good predictor for early
      recurrence of CMV infection, and would be useful for monitoring the response to
      antiviral therapy.

PMID- 9175807
TI  - A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in
      heart and lung transplant recipients.
AB  - BACKGROUND: Cyclosporine (CsA) is a potent immunosuppressive drug widely used in
      organ transplantation and in the treatment of autoimmune diseases (1, 2).
      However, its common nephrotoxic effect is a major limiting factor. Short-term CsA
      treatment has been shown to cause reversible renal vasoconstriction, whereas long
      term treatment can lead to an afferent arteriolopathy and chronic renal failure.
      METHODS: We performed a randomized controlled trial to examine the short-term
      renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients.
      Sixteen patients each were randomized to receive a 6-week course of verapamil or
      control treatment (atenolol in hypertensive patients and placebo in normotensive
      patients) 1-2 months after transplantation. An 8-hr sequential clearance study of
      inulin and p-aminohippuric acid for estimating glomerular filtration rate and
      renal plasma flow, respectively, was performed at baseline and at completion of
      study. The integral area under the curve of the clearance parameter over 8 hr was
      then calculated to generate a clearance-time index. RESULTS: There was no
      difference in the clearance-time indices for inulin and p-aminohippuric acid
      between the two groups at baseline. However, at the completion of study, the
      within-group change in the glomerular filtration rate clearance-time index was
      different between the verapamil and control groups (48+/-20 vs. -35+/-17
      ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal
      plasma flow, but did not reach statistical significance. Mean arterial blood
      pressure and whole-blood CsA levels did not differ between the two groups during
      the study. Verapamil treatment was also associated with a decrease in CsA dose
      requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at
      completion; P<0.001) without any significant change in trough whole blood CsA
      levels. Rejection episodes did not differ between the two groups. CONCLUSIONS:
      The use of verapamil in the heart or lung transplant recipients may therefore
      provide both renal protective effects and cost savings.

PMID- 9175808
TI  - Multicenter evaluation of the flow cytometry T-cell crossmatch: results from the
      American Society of Histocompatibility and Immunogenetics-College of American
      Pathologists proficiency testing program.
AB  - BACKGROUND: The performance characteristics and interlaboratory comparisons of
      the T-cell flow cytometry crossmatch remain largely unknown. METHODS: This study
      was performed using data from the ASHI-CAP proficiency testing program. Four
      unknown sera and two unknown cells were sent to participating laboratories twice
      a year for 4 years. RESULTS: In one survey in which different crossmatch
      techniques were compared, flow cytometry was slightly more sensitive than the
      antiglobulin method and considerably more sensitive than direct cytotoxicity.
      However, the proportion of participants in any given survey detecting antibodies
      in all sera expected to be positive was 50-60% and has not changed over the
      years. Failure to detect antibodies correlated with low antibody concentration,
      diluting the unknown serum by the testing laboratory, and with the instrument
      used. False positive results with normal sera were infrequent. Fluorescence
      intensity values were not standardized and were highly variable, but when
      fluorescence units reported by individual laboratories were divided by their own
      positive-negative cutoff values, results from different centers were more
      comparable. In general, fluorescence-to-cutoff ratios >5 correlated with
      complement binding activity, whereas values <5 denoted concentrations below those
      required to fix complement. CONCLUSIONS: Flow cytometry, as used by most centers,
      is highly sensitive and allows relative antibody quantitation. Furthermore, the
      data define objective parameters that may help to standardize the test and
      improve its predictive value in clinical transplantation.

PMID- 9175809
TI  - Xenograft rejection of porcine islet-like cell clusters in normal, interferon
      gamma, and interferon-gamma receptor deficient mice.
AB  - BACKGROUND: The aim of the present study was to evaluate the role of the T-cell
      cytokine interferon (IFN)-gamma in mediating macrophage activation in xenograft
      rejection. METHODS: For this purpose, fetal porcine islet-like cell cluster (ICC)
      transplants were placed under the renal capsule of normal mice and mice with a
      homozygous targeted disruption of the IFN-gamma or the IFN-gamma receptor gene.
      Some of the mice were continuously infused with cyclosporine (CsA, 12.4 mg/kg
      body weight/day) or CsA vehicle by subcutaneously implanted osmotic pumps.
      Histological evaluation of the xenografts was performed 6 or 12 days after
      transplantation. RESULTS: All animals, irrespective of recipient group, readily
      rejected the ICC xenograft, although the rejection process was slightly delayed
      in mice deficient in IFN-gamma. Analysis of the infiltrating cells within the
      xenograft in knockout mice revealed a pattern similar to that found in control
      animals. Six days after transplantation, there was an abundant infiltration of
      macrophages (Mac-1, F4/80, and major histocompatibility complex II markers) in
      the ICC grafts. Quite in contrast, there was only a low to moderate number of T
      cells (CD3 marker) present in the ICC grafts. Treatment with CsA had no effect on
      the rejection process. In grafts removed from mice with a disruption of the IFN
      gamma gene, occasional surviving endocrine cells, and in some cases also a few
      intact ICC, were found within the otherwise obliterated xenograft. Few or no
      surviving endocrine cells were found in the grafts obtained from the other groups
      of mice. CONCLUSIONS: Thus, the present study demonstrates that macrophage
      activation, and subsequent destruction of an ICC xenograft, can operate in the
      absence of IFN-gamma in the pig-to-mouse model.

PMID- 9175810
TI  - Intact pig pancreatic islet function in the presence of human xenoreactive
      natural antibody binding and complement activation.
AB  - BACKGROUND: The expression of xenogeneic epitopes and the activation of human
      complement by adult pig islets after prolonged culture have hitherto not been
      described. MATERIALS AND METHODS: Freshly isolated and cultured islets were
      analyzed by fluorescence-activated cell sorter analysis, fluorescence microscopy,
      and immunohistology for expression of Gal(alpha1,3)Gal epitopes, binding of human
      xenoreactive natural antibodies (XNA), and complement deposition. RESULTS:
      Freshly isolated and cultured islets showed detectable Gal(alpha1,3)Gal
      expression and human XNA binding limited to intraislet capillary endothelial
      cells. No significant modification in Gal(alpha1,3)Gal expression and human XNA
      binding levels was detected in adult pig islets cultured for up to 4 days
      compared with freshly isolated islets. Incubation of pig islets with human serum
      demonstrated the deposition of C3, C4, and membrane attack complex, but not
      factor B with a similar pattern to XNA. However C3 and C4 showed a more
      widespread deposition. Despite complement activation, no cytotoxic effect on
      islets was detected after 4 hr of incubation with human serum capable of killing
      porcine endothelial cells. Even after 4 days of culture in 50% intact human
      serum, pig islets retained both their normal morphology and a normal insulin
      response to glucose stimulation. CONCLUSIONS: Neither islet cell lysis nor, more
      importantly, any alteration in beta cell function occurred, which suggests that
      adult pig islets may not be directly damaged by serum after xenotransplantation
      in humans. Nevertheless, complement activation in vivo could trigger rapid
      cellular rejection mechanisms through islet cell opsonization and release of
      bioactive fragments.

PMID- 9175812
TI  - Pancreas and kidney allograft-infiltrating cells in simultaneous pancreas-kidney
      transplantation.
AB  - BACKGROUND: Rejection after pancreas-kidney transplantation may occur isolated or
      concurrently in both grafts. To get more insight into the cellular mechanisms
      underlying these rejection episodes, we compared the functional characteristics
      of pancreas and kidney graft-infiltrating T cells. METHODS: Graft-infiltrating T
      cell (GIC) lines were cultured from simultaneously taken pancreas and kidney
      biopsies from eight patients. CD4 to CD8 ratios were determined by fluorescence
      activated cell sorter and cytotoxicity toward donor proximal tubular epithelial
      cells (PTEC) and donor spleen cells (DSC) using a standard cytotoxicity assay.
      Cytokine production was determined by enzyme-linked immunosorbent assay. RESULTS:
      CD4 to CD8 ratios were comparable between the pancreas and kidney lines for each
      patient, but differences were observed in cytotoxicity toward PTEC and DSC. For
      four of eight patients, the lysis of PTEC by pancreas GIC was less than the lysis
      induced by kidney GIC. This was also seen in three of five patients for lysis of
      DSC. The specificity of GIC lines toward mismatched donor antigens was studied
      for two patients and appeared to be comparable for pancreas and kidney. Most GIC
      lines produced interferon (IFN)-gamma (75.5+/-22.7 pg/ml), but no IL-10,
      indicating that the cell lines consisted primarily of Th1 and type 1 CD8+ cells.
      Mean production of IL-6 was 465.6+/-193.6 pg/ml. No major differences were
      observed between kidney and pancreas GIC for either cytokine. CONCLUSIONS: We
      conclude that pancreas and kidney GIC lines have the same phenotype, cytokine
      production, and allospecificity. Differences were, however, seen for lysis of
      PTEC and DSC, suggesting that tissue-specific antigens might play a role.

PMID- 9175811
TI  - Analysis of the B7 costimulatory pathway in allograft rejection.
AB  - BACKGROUND: Blockade of the B7/CD28 costimulation pathway with the fusion
      protein, CTLA4-Ig, has been shown to prolong allograft survival in numerous
      rodent models, suggesting that this pathway is functionally important in the
      allograft rejection response. This pathway is complex and consists of at least
      the B7-1, B7-1a, B7-1cyt II, and B7-2 molecules on the antigen-presenting cell
      and CD28 and CTLA4 molecules on the T cell. METHODS: The intragraft transcript
      expression of the B7 molecules and their counterreceptors was defined using
      reverse transcriptase-polymerase chain reaction in the vascularized mouse cardiac
      allograft model. In addition, the functional significance of these molecules was
      investigated both in vitro in the mixed leukocyte response (MLR) and in vivo in
      the vascularized mouse cardiac allograft model. RESULTS: Intragraft expression of
      B7-1, B7-1a, B7-1cyt II, B7-2, CD28, and CTLA4 transcripts is up-regulated in
      allografts when compared with both normal untransplanted hearts and syngeneic
      transplants at between 5 and 12 days after transplant. Both anti-B7-1 and anti-B7
      2 monoclonal antibodies alone inhibited T-cell proliferation in the MLR, however,
      equivalent maximal inhibition was obtained by a combination of these agents or by
      CTLA4-Ig. Likewise, in the mouse cardiac allograft model, both anti-B7-1 and anti
      B7-2 modestly prolonged graft survival. However, an increased survival was
      obtained with either a combination of anti-B7-1 and anti-B7-2 or CTLA4-Ig.
      Blockade of the B7/CD28 pathway in the MLR using T cells from CD28 knockout mice
      had no effect on the proliferative response. Likewise, blockade of the B7/CD28
      pathway did not effect the rate of rejection of cardiac allografts by CD28
      knockout recipients. CONCLUSIONS: These data suggest that both B7-1 and B7-2 have
      an important role in allograft rejection in the mouse vascularized cardiac
      allograft model.

PMID- 9175813
TI  - Usefulness of DNA viral load quantification for cytomegalovirus disease
      monitoring in renal and pancreas/renal transplant recipients.
AB  - BACKGROUND: The purpose of this prospective study was to evaluate the usefulness
      of quantifying DNA-cytomegalovirus (CMV) load for the diagnosis and monitoring of
      CMV disease among renal and pancreas transplant patients under immunosuppressive
      drugs. METHODS: A longitudinal study was conducted among 34 consecutive,
      unselected renal and pancreas/renal transplanted patients in our unit. During the
      first 3 posttransplant months, weekly monitoring of CMV infection and CMV disease
      was done, involving the determination of viremia by the shell vial assay,
      qualitative DNAemia by semi-nested polymerase chain reaction (PCR) and
      quantitative DNAemia by the hybrid capture system (HCS), a new and original
      hybridization method (337 samples were collected for each test). Qualitative and
      quantitative DNAemia results were blinded to physicians and three grades of
      disease were defined according to CMV related symptom occurrence. RESULTS: PCR
      was the most sensitive (100%) but the least specific (78%) method for the
      diagnosis of CMV disease. HCS was specific for CMV genome detection, sensitive
      and reproducible. Blood DNA levels above 60 pg/ml were predictive of severe or
      moderate CMV disease (sensitivity, 92%; specificity, 100%). A significant
      decrease in viral load was observed after ganciclovir administration, and a
      positive PCR or HCS result at the end of the antiviral treatment was associated
      with relapse of CMV infection or disease. CONCLUSIONS: It is concluded that
      quantitative DNAemia detection, with this new commercially available method, can
      predict disease and may be useful for a rational evaluation of ganciclovir
      preemptive therapy in such patients.

PMID- 9175814
TI  - Apoptosis of mononuclear cell infiltrates in cardiac allograft biopsy specimens
      questions studies of biopsy-cultured cells.
AB  - During acute rejection, CD4 and CD8 T cells infiltrate the myocardium and cause
      myocyte death and dropout. CD4 and CD8 cells use a number of cytotoxic
      mechanisms, including fas-fas ligand interactions, which lead to apoptotic death.
      Since fas is expressed on myocytes, we investigated endomyocardial biopsy
      specimens from cardiac transplant patients to determine whether apoptosis is one
      of the mechanisms of cell death in acute rejection. Serial sections of individual
      endomyocardial biopsy specimens from patients histologically diagnosed as having
      grade 3A rejection (n=22 biopsy specimens), biopsy specimens showing a typical
      "Quilty effect" (n=10), and specimens with concurrent grade 3A rejection and the
      Quilty effect (n=6) were evaluated using the C-terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique for
      frequency of apoptosis in myocytes and mononuclear cell infiltrates. None of the
      examined sections showed detectable evidence of apoptotic myocytes, even within
      regions clearly showing myocyte damage. Of interest was our consistent finding
      that 85-98% of mononuclear cell infiltrates within biopsy specimens scored as
      having grade 3A rejection had undergone apoptosis. In marked contrast, 9 of the
      10 specimens with Quilty lesions showed <5% apoptotic mononuclear cells in the
      endomyocardial infiltrates. Of further interest was our finding of 85-98%
      apoptotic mononuclear cell infiltrates within Quilty lesions associated with
      biopsy specimens scored as having grade 3A rejection. The frequency of apoptotic
      cells determined by the TUNEL technique was confirmed by histological examination
      of the morphology of the cells and with a technique that involves detection of c
      jun. These results prompt a note of caution in the interpretation of data on the
      phenotype, cytokine profile, Vbeta T cell receptor repertoire, and donor
      specificity of mononuclear cells cultured and propagated from such cardiac biopsy
      specimens. The possible reasons for apoptosis of graft-infiltrating mononuclear
      cells are discussed.

PMID- 9175815
TI  - Pretransplant administration of a single donor class I major histocompatibility
      complex molecule is sufficient for the indefinite survival of fully allogeneic
      cardiac allografts: evidence for linked epitope suppression.
AB  - BACKGROUND: Allograft survival can be prolonged by the administration of
      alloantigen(s) before transplantation. Blood transfusion is the commonest form of
      alloantigen pretreatment currently used in clinical practice. However, for
      recipients of organs from cadaver donors, it is not possible to predict the
      identity of the organ donor in advance. Therefore, it is highly unlikely that all
      the alloantigens expressed by a cadaver organ donor will be represented in the
      alloantigen pretreatment inoculum. We have previously shown that it is not
      necessary to expose the recipient to the full complement of donor alloantigens to
      induce long-term survival of a subsequent cardiac allograft. Here, we
      investigated the in vivo mechanism responsible for this phenomena. METHODS:
      Unresponsiveness to the mouse MHC class I molecule Kb was induced in CBA.Ca (H2k)
      recipients by administration of bone marrow cells from transgenic CBA mice, CBK
      (H2k + Kb) before transplantation of fully allogeneic and F1 vascularized cardiac
      allografts. RESULTS: Pretreatment with CBK bone marrow cells resulted in the long
      term survival of all cardiac allografts expressing H2-Kb. For example, C57BL/10
      (H2b) and (CBKxBALB/c) F1 (H2k,d + Kb) cardiac allografts were accepted by
      recipients treated with CBK bone marrow cells before transplantation. In
      contrast, allografts that did not express Kb, such as BALB/c (H2d) or
      (CBAxBALB/c) F1 (H2k,d), were rejected acutely, with a median survival time (MST)
      of 7 and 6 days, respectively, in recipients treated with CBK bone marrow cells.
      Furthermore, when recipients pretreated with CBK bone marrow cells were grafted
      with a BALB/c heart and a CBK heart simultaneously, the BALB/c hearts were
      rejected (MST=10 days), whereas the CBK hearts were accepted. By contrast, in the
      maintenance phase (i.e., after transplantation), recipients with long-term
      surviving (CBKxBALB/c) F1 hearts (> 100 days) were found to accept BALB/c hearts
      indefinitely, whereas fourth-party B10.S (H2s) grafts were rejected (MST=7.5
      days). This indicated that the allografts bearing Kb could tolerize recipients to
      other alloantigens expressed by the transplanted heart. CONCLUSIONS: These data
      provide clear evidence for linked epitope suppression in the induction of
      operational tolerance in vivo.

PMID- 9175816
TI  - Inhibition of CD26/dipeptidyl peptidase IV activity in vivo prolongs cardiac
      allograft survival in rat recipients.
AB  - The CD26 antigen, one of the major costimulatory molecules in T cell activation,
      was shown to possess dipeptidyl peptidase IV (DPP IV) activity. Previously, we
      demonstrated that immunosuppressed kidney transplant patients exhibit lower DPP
      IV serum activity as compared with healthy individuals. In the present study, we
      analyzed the role of CD26/DPP IV in the immune cascade triggered by organ
      transplantation and leading to acute rejection of cardiac allografts in rat
      recipients. Transplantation of hearts from (Lewis x Brown Norway)F1 donors into
      Lewis hosts resulted in an early (24 hr) increase in cellular CD26 expression,
      followed by a rise in DPP IV serum activity, which peaked at day 6, i.e., before
      the time of actual graft loss. Specific targeting of DPP IV activity with a
      novel, low-molecular-weight inhibitor of the diphenyl-phosphonate group
      (prodipine) abrogated acute rejection and prolonged cardiac allograft survival to
      14.0+/-0.9 days (P<0.0001). Prodipine treatment prevented the early peak of
      cellular CD26 expression and thoroughly suppressed systemic DPP IV activity. The
      inhibition of DPP IV was associated with severely impaired host cytotoxic T
      lymphocyte responses in vitro. These results demonstrate the role of CD26/DPP IV
      in alloantigen-mediated immune regulation in vivo and provide the first direct
      evidence that CD26/DPP IV plays an important role in the mechanism of allograft
      rejection. The model of targeting CD26/DPP IV may reveal essential interactions
      on the level of costimulatory alternate T cell activation pathways, allowing a
      more subtle approach for more selective immunosuppression in transplant
      recipients.

PMID- 9175817
TI  - Topical interleukin 1 receptor antagonist promotes corneal transplant survival.
AB  - BACKGROUND: Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a
      critical role in initiating and maintaining immunogenic inflammation. We
      performed a series of experiments to determine whether the topical application of
      IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the
      murine model of orthotopic allotransplantation. METHODS: For all experiments,
      C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor
      histocompatibility-disparate) eyes. "High-risk" transplants were transplants that
      had been sutured into BALB/c recipient beds with corneal neovascularization
      induced by placement of three interrupted sutures in the host cornea 2 weeks
      earlier. Both risk groups were divided in a masked fashion into treatment
      subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium
      hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were
      evaluated for 8 weeks after surgery for signs of rejection. At the end of follow
      up, corneal specimens were processed for enumeration of Langerhans cells and
      histopathological evaluation. RESULTS: Survival rates of both normal-risk and
      high-risk transplants increased significantly among the IL-1ra-treated animals
      compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and
      Kaplan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk
      IL-1ra-treated grafts had significantly less inflammation and Langerhans cells
      infiltration compared with untreated controls. CONCLUSIONS: Topical treatment
      with IL-1ra has a significantly positive effect in promoting corneal allograft
      survival.

PMID- 9175818
TI  - Sequential monitoring of urine-soluble interleukin 2 receptor and interleukin 6
      predicts acute rejection of human renal allografts before clinical or laboratory
      signs of renal dysfunction.
AB  - BACKGROUND: The significance of noninvasive techniques to the early diagnosis of
      acute rejection in kidney transplants remains elusive. In this study, we examined
      whether an early posttransplant increase in serum- and urine-soluble interleukin
      (IL) 2 receptor (sIL-2R) and IL-6 levels predicted acute rejection. METHODS:
      Sequential determinations of serum and urine sIL-2R and IL-6 were performed in
      the first 30 postoperative days in 40 renal transplant patients. Changes during
      the posttransplant period observed in 26 patients who had one or more episodes of
      acute rejection (group A) were compared with those recorded in 14 patients who
      did not experience acute rejection of their graft (group B). RESULTS: Serum sIL
      2R was higher than normal in patients of groups A and B without statistical
      differences between the two groups. In the first 3 days after transplantation,
      urinary sIL-2R was higher than normal in group A but not in group B. Urinary sIL
      2R at days 2 and 3 was significantly higher (P<0.05) in group A than in group B.
      In the first 5 days after transplantation, urinary IL-6 was persistently higher
      than normal in group A, whereas it progressively decreased to normal value on day
      4 in group B. Sudden increases (doubling within 24 hr) in urine IL-6 preceded
      clinical diagnosis of acute rejection by a mean period of 2 days, with an 87%
      sensitivity and a 64% specificity, and also predicted recurrent rejection
      episodes. CONCLUSIONS: Sequential monitoring of urinary sIL-2R and IL-6 levels
      does allow very early diagnosis of rejection without invasive procedures.
      Specifically, high urinary sIL-2R in the first 5 posttransplant days identifies
      the subgroup of patients at risk. In the subsequent days, a sudden increase in
      urinary IL-6 occurs in those of the above patients who will indeed reject their
      graft.

PMID- 9175819
TI  - Effect of HLA-DR-shared blood transfusion on the clinical outcome of heart
      transplantation.
AB  - Pretransplant blood transfusion can have a favorable effect on renal and cardiac
      graft survival. In a previous study, we found that HLA-DR-shared blood
      transfusions led to better graft survival after kidney transplantation. In the
      present study, we tried to confirm and extend these findings by analyzing the
      effects of blood transfusion on the clinical course following heart
      transplantation. According to a predefined protocol, cardiac allograft recipients
      received random blood transfusion before surgery. A beneficial effect of HLA-DR
      shared blood transfusion could be observed on survival and on the number of
      rejection episodes. Patients who had received an HLA-mismatched transfusion had
      significantly more infections, and in this group, more patients died due to
      malignancies. To study a possible role of immunomodulating T cells, patients who
      had or had not received prophylactic anti-T cell therapy were analyzed
      separately. In both groups, a beneficial effect of HLA-DR-shared blood
      transfusion could be demonstrated. These results indicate that the administration
      of HLA-DR-matched blood transfusion before transplantation is beneficial in
      cardiac allograft recipients, and that regulatory T cells are either not directly
      involved or (partly) resistant to modulation by anti-T cell antibody therapy.

PMID- 9175820
TI  - Kaposi's sarcoma in liver transplant recipients on FK506: two case reports.
AB  - We report two cases of Kaposi's sarcoma (KS) after orthotopic liver
      transplantation for cirrhosis of the liver related to hepatitis C virus. Both
      cases were Saudi-born Arabs who were negative for human immunodeficiency virus;
      one patient was receiving FK506 plus prednisolone, and the other patient was
      receiving FK506. One patient died of fulminant multicentric KS. The other
      patient, with lesions confined to the lower limbs, is still alive. These are the
      first case reports of KS in liver transplant recipients in the Kingdom of Saudi
      Arabia and, to our knowledge, these are the first case reports of KS in liver
      transplant recipients on FK506. All previous reports were related to either
      cyclosporine or conventional immunosuppressive therapy, i.e., azathioprine plus
      prednisolone.

PMID- 9175821
TI  - Orthotopic liver transplantation for veno-occlusive disease complicating
      autologous bone marrow transplantation.
AB  - BACKGROUND: Veno-occlusive disease of the liver is a serious and often life
      threatening complication after bone marrow transplantation. Although risk factors
      for the development of veno-occlusive disease have been postulated, there is no
      precise method for accurately identifying those patients who are at risk and for
      whom early intervention and treatment would have maximum potential benefit. Liver
      transplantation has been advocated as a treatment for veno-occlusive disease in
      selected patients. METHODS: In this report, we describe a patient who underwent
      liver transplantation for life-threatening veno-occlusive disease after
      autologous bone marrow transplantation for acute lymphoblastic leukemia. RESULTS:
      Liver engraftment was achieved, but the patient developed Pneumocystis pneumonia,
      which failed to respond to pentamidine. The patient died 6 months after liver
      transplantation. CONCLUSIONS: While acknowledging the limited experience of
      orthotropic liver transplantation in this patient population, we suggest its
      consideration as a feasible, potentially beneficial treatment option in patients
      with severe veno-occlusive disease after bone marrow transplantation.

PMID- 9175822
TI  - Extending the limit on the size of adult recipient in living donor liver
      transplantation using extended right lobe graft.
AB  - The feasibility of adult-to-adult living donor liver transplantation (LDLT) is
      restricted by the adequacy of the graft size. A left lobe graft from a relatively
      small donor will not meet the metabolic demand of a larger recipient. We report a
      successful LDLT performed on a 90-kg man using an extended right lobe graft
      weighing 910 g from his relatively smaller-size brother. The donor-to-recipient
      body weight ratio was only 0.82. No homologous blood transfusion was required for
      the donor, and the donor recovered uneventfully except for mild transient
      hyperbilirubinemia. The graft provided adequate function for the metabolic needs
      of the recipient despite postoperative septic complications. Both donor and
      recipient were well with normal liver function at 4 months after operation. LDLT
      using the extended right lobe liver graft can extend the limit on the size of the
      adult recipient and may be a viable option even when the donor is relatively
      small compared with the recipient.

PMID- 9175823
TI  - Infections after renal allograft failure in patients with or without low-dose
      maintenance immunosuppression.
AB  - BACKGROUND: Failed renal allografts are sometimes left in situ for additional
      clearance and urine production during hemodialysis or peritoneal dialysis, and
      low-dose immunosuppressive medication is often continued in such patients. We
      compared the morbidity and mortality due to infections between patients with
      (group A) or without (group B) low-dose immunosuppression (i.e.,
      transplantectomy). METHODS: In a hospital-based cohort study, we analyzed data
      from patient files. We evaluated 37 patients who received 42 kidney
      transplantations between May 1975 and November 1995. RESULTS: A total of 2.28 vs.
      0.68 infections/patient-year were found in groups A and B, respectively. The odds
      ratio of one or two infections developing for patients in group A compared with
      group B was 14.2 (95% confidence interval, 1.4-143.4; P<0.025) and 4.3 (95%
      confidence interval, 1.1-17.3; P<0.04). A total of five lethal infections were
      found in group A; no lethal infections were found in group B. CONCLUSIONS: The
      increase in serious and life-threatening infections associated with even low-dose
      immunosuppression argues in favor of discontinuation of these drugs. The removal
      of failed renal allografts should be considered.

PMID- 9175824
TI  - Mycophenolate mofetil and prednisone as maintenance treatment after kidney
      transplantation.
AB  - BACKGROUND: Hemolytic uremic syndrome (HUS) is an infrequent but severe
      complication of kidney transplantation. Cyclosporine-induced microangiopathy may
      be the causative factor in allograft recipients with HUS. In transplant
      recipients with HUS, discontinuation of cyclosporine is generally advised. This
      often leads to loss of the graft. METHODS: An adult kidney transplant recipient
      developed HUS in the third week after transplantation. Maintenance
      immunosuppression was changed to mycophenolate mofetil and prednisone after
      cyclosporine was discontinued. RESULTS: The change in immunosuppressive therapy
      led to remission of the HUS and stable graft function. CONCLUSIONS: In transplant
      recipients receiving cyclosporine who suffer from HUS, the possibility of
      conversion from cyclosporine to mycophenolate mofetil should be considered. As
      this case shows, complete remission of HUS and maintenance of the graft are
      possible.

PMID- 9175825
TI  - Combined heart and kidney transplantation in a child: will we need it more in the
      future?
AB  - A 12-year-old girl affected by idiopathic dilated cardiomyopathy and renal
      failure was referred to our institution for cardiac transplantation. A
      simultaneous heart-kidney transplantation from the same donor was decided. The
      immunosuppression schedule consisted of azathioprine, antithymocyte globulin,
      steroids, and cyclosporine. At a follow-up visit at 24 months after
      transplantation, no episodes of heart or kidney rejection had occurred and
      cardiac and renal function were good. Concomitant failure of heart and kidney is
      well known in the literature, but it appears to be more frequent in adult as
      compared with the pediatric population. This is the first case of combined heart
      and kidney transplantation in a child. Because of the successful outcome and good
      follow-up, the number of combined organ transplantations will most likely
      increase in the future.

PMID- 9175826
TI  - Failure of ganciclovir treatment associated with selection of a ganciclovir
      resistant cytomegalovirus strain in a lung transplant recipient.
AB  - We report the case of a lung transplant recipient with progressive
      cytomegalovirus (CMV) disease due to a resistant CMV strain emerging under
      ganciclovir (GCV) therapy. A discriminative polymerase chain reaction (PCR)
      assay, designed to detect the resistance-related V460 mutation within the viral
      enzyme UL97, revealed the presence of a mutated strain in a heterogeneous isolate
      51 days after transplantation. The conventional antiviral susceptibility assay
      had failed to demonstrate resistance to GCV. Under prolonged GCV therapy, the
      mutated strain dominated the wild-type strain, as shown by the PCR assay. This
      domination led to laboratory resistance, associated with recurrent fever and
      progressively severe retinitis. As this discriminative PCR assay was shown to be
      effective in detecting mutated strains that constitute a minority in the virus
      load, it should allow better management of patients with CMV disease.

PMID- 9175827
TI  - Influence of acinar tissue contamination on encapsulated pancreatic islets:
      morphological and functional studies.
AB  - BACKGROUND: The present study concerns the influence of acinar contamination on
      pancreatic islets encapsulated in an artificial membrane (AN 69). METHODS: Pure,
      handpicked pancreatic islets were contaminated by the addition of acinar tissue
      (ratio, 1:1). The morphological aspect and insulin release of both pure (n=12)
      and contaminated (n=12) encapsulated islets were assessed after 10 days of
      culture or implantation in the peritoneal cavity of rats. RESULTS: After
      implantation, the encapsulated islets, irrespective of their purity, were totally
      altered, whereas the morphological aspect of the cultivated islets remained
      intact only in the absence of acinar tissue contamination. This contamination
      induced a significant decrease in the stimulation index of insulin release. The
      stimulation index decreased by 42% for fresh islets and by 52% and 34% for
      cultivated and implanted islets, respectively, without modification in their
      basal release of insulin. CONCLUSIONS: The acinar tissue proved detrimental to
      the encapsulated implanted and cultivated islets.

PMID- 9175828
TI  - IL-7 receptor and VDJ recombination: trophic versus mechanistic actions.

PMID- 9175829
TI  - Tuning antigen receptor signaling by CD22: integrating cues from antigens and the
      microenvironment.

PMID- 9175830
TI  - Peptide antigen treatment of naive and virus-immune mice: antigen-specific
      tolerance versus immunopathology.
AB  - Peptide-specific down-regulation of T cell responses may represent a powerful
      tool to intervene in autoimmune diseases or graft rejections. It is therefore
      important to know whether peptide treatment tolerizes both naive and antigen
      experienced memory T lymphocytes. Here we show that a major histocompatibility
      complex class I binding peptide, derived from the glycoprotein (GP33 peptide) of
      lymphocytic choriomeningitis virus (LCMV), specifically tolerized naive cytotoxic
      T lymphocytes (CTL) when administered three times intraperitoneally in incomplete
      Freund's adjuvants. However, in the presence of GP33-specific memory CTL in LCMV
      primed mice, the same treatment had a general immunosuppressive effect on
      unrelated third-party antigen-specific T cell responses and caused severe
      immunopathological damage to the spleen.

PMID- 9175831
TI  - Borrelia burgdorferi P35 and P37 proteins, expressed in vivo, elicit protective
      immunity.
AB  - p35 and p37 are Borrelia burgdorferi genes encoding 35 and 37 kDa proteins. The
      gene products were identified by differential screening of a B. burgdorferi
      expression library with sera from B. burgdorferi infected- and B. burgdorferi
      hyperimmunized mice. Northern blot and RT-PCR analyses confirmed that these genes
      were selectively expressed in vivo. ELISA, using P35 and P37, showed that
      infected mice (5 of 5, 100%) and patients (31 of 43, 72%) with Lyme borreliosis
      developed P35 or P37 antibodies. Mice developed peak IgG titers to P35 and P37
      within 30 days, followed by decline. Mice given both P35 and P37 antisera were
      protected from challenge with 10(2) B. burgdorferi, and P35 and P37 antisera also
      afforded protection when administered 24 hr after spirochete challenge. The use
      of in vivo-expressed antigens such as P35 and P37 represents a new approach for
      Lyme disease serodiagnosis and for understanding the role of B. burgdorferi
      specific immune responses in host immunity.

PMID- 9175832
TI  - IL-4 rapidly produced by V beta 4 V alpha 8 CD4+ T cells instructs Th2
      development and susceptibility to Leishmania major in BALB/c mice.
AB  - BALB/c mice develop aberrant T helper 2 (Th2) responses and suffer progressive
      disease after infection with Leishmania major. These outcomes depend on the
      production of interleukin-4 (IL-4) early after infection. Here we demonstrate
      that the burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hr
      after infection, occurs within CD4+ T cells that express V beta 4 V alpha 8 T
      cell receptors. In contrast to control and V beta 6-deficient BALB/c mice, V beta
      4-deficient BALB/c mice were resistant to infection, demonstrating the role of
      these cells in Th2 development. The early IL-4 response was absent in these mice,
      and T helper 1 responses occurred following infection. Recombinant LACK antigen
      from L. major induced comparable IL-4 production in V beta 4 V alpha 8 CD4+
      cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major
      is produced by a restricted population of V beta 4 V alpha 8 CD4+ T cells after
      cognate interaction with a single antigen from this complex organism.

PMID- 9175833
TI  - Serial backcross mapping of multiple loci associated with resistance to
      Leishmania major in mice.
AB  - Resistance or susceptibility of inbred mouse strains to the parasite Leishmania
      major correlates with CD4+ T cell responses of the Th1 or Th2 subsets,
      respectively. To evaluate the genetic basis for this difference, resistant B10.D2
      mice were backcrossed onto susceptible BALB/c mice for five generations with
      selection for resistance. Candidate resistance loci were identified by high
      frequency of heterozygosity in resistant N5 backcross mice. Loci on chromosomes
      6, 7, 10, 11, 15, and 16 were associated with resistance, demonstrating the
      multigenic nature of this phenotype. The presence of all six loci was not
      necessary to confer resistance and no single locus was required. Rather, a
      variety of combinations of these loci may be capable of interacting to confer
      resistance.

PMID- 9175834
TI  - Impaired Th2 subset development in the absence of CD4.
AB  - Prior studies in CD4-deficient mice established the capacity of T helper (Th)
      lineage cells to mature into Th1 cells. Unexpectedly, challenge of these mice
      with Nippostrongylus brasiliensis, a Th2-inducing stimulus, failed to result in
      the development of Th2 cells. Additional studies were performed using CD4+ or CD4
      CD8- (double-negative) T cell receptor (TCR) transgenic T cells reactive to LACK
      antigen of Leishmania major. Double-negative T cells were unable to develop into
      Th2 cells in vivo, and, unlike CD4+ T cells, could not be primed for interleukin
      4 production in vitro. Similarly, CD4+ TCR transgenic T cells primed on antigen
      presenting cells expressing mutant MHC class II molecules unable to bind CD4 did
      not differentiate into Th2 cells. These data suggest that interactions between
      the TCR, MHC II-peptide complex and CD4 may be involved in Th2 development.

PMID- 9175835
TI  - Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and
      induces lymphocyte aggregation.
AB  - Tip of herpesvirus saimiri associates with Lck and down-regulates Lck-mediated
      activation. We identified a novel cellular Tip-associated protein (Tap) by a
      yeast two-hybrid screen. Tap associated with Tip following transient expression
      in COS-1 cells and stable expression in human Jurkat-T cells. Expression of Tip
      and Tap in Jurkat-T cells induced dramatic cell aggregation. Aggregation was
      likely caused by the up-regulated surface expression of adhesion molecules
      including integrin alpha, L-selectin, ICAM-3, and H-CAM. Furthermore, NF-kappaB
      transcriptional factor of aggregated cells had approximately 40-fold higher
      activity than that of parental cells. Thus, Tap is likely to be an important
      cellular mediator of Tip function in T cell transformation by herpesvirus
      saimiri.

PMID- 9175836
TI  - Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its
      interaction with clathrin-associated adaptor complex AP-2.
AB  - CTLA-4 is a costimulation receptor that binds to the same ligands, CD80 and CD86,
      as CD28 with high affinity and is transiently expressed on the cell surface of
      activated T cells. CTLA-4 delivers an inhibitory signal through association of a
      phosphotyrosine-containing motif in the cytoplasmic domain with Syp tyrosine
      phosphatase. We now demonstrate that CTLA-4 interacts with the mu2 subunit of the
      plasma membrane-associated adaptor complex, AP-2, through the same motif involved
      in the interaction with Syp, except that the interaction with mu2 requires
      unphosphorylated tyrosine. The interaction with mu2 likely induces rapid
      internalization of CTLA-4 from the cell surface. Our results suggest that the
      phosphorylation state of a single tyrosine residue determines whether CTLA-4
      delivers a negative signal or is internalized.

PMID- 9175837
TI  - Induction of MHC class I expression by the MHC class II transactivator CIITA.
AB  - Major histocompatibility complex (MHC) class I-deficient cell lines were used to
      demonstrate that the MHC class II transactivator (CIITA) can induce surface
      expression of MHC class I molecules. CIITA induces the promoter of MHC class I
      heavy chain genes. The site alpha DNA element is the target for CIITA-induced
      transactivation of class I. In addition, interferon-gamma (IFNgamma)-induced MHC
      class I expression also requires an intact site alpha. The G3A cell line, which
      is defective in CIITA induction, does not induce MHC class I antigen and promoter
      in response to IFNgamma. Trans-dominant-negative forms of CIITA reduce class I
      MHC promoter function and surface antigen expression. Collectively, these data
      argue that CIITA has a role in class I MHC gene induction.

PMID- 9175838
TI  - Site alpha is crucial for two routes of IFN gamma-induced MHC class I
      transactivation: the ISRE-mediated route and a novel pathway involving CIITA.
AB  - The constitutive and cytokine-induced levels of major histocompatibility (MHC)
      class I expression are tightly controlled at the transcriptional level. In this
      study, it is shown that the cis-acting regulatory element site alpha of the MHC
      class I promoter is essential for the IFN gamma-induced transactivation of MHC
      class I gene expression through the ISRE. Moreover, it was discovered that the
      class II transactivator (CIITA), which is itself under the control of the IFN
      gamma induction pathway, strongly transactivates MHC class I gene expression and
      exerts its activity through site alpha. Therefore, site alpha is a crucial
      regulatory element, mediating the classic route of IFN gamma induction via the
      ISRE as well as a novel route of MHC class I transactivation involving CIITA.

PMID- 9175839
TI  - The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation
      by TAP.
AB  - Human cytomegalovirus (HCMV) inhibits MHC class I antigen presentation by a
      sequential multistep process involving a family of unique short (US) region
      encoded glycoproteins. US3 retains class I molecules, whereas US2 and US11
      mediate the cytosolic degradation of heavy chains by the proteosomes. In US6
      transfected cells, however, intracellular transport of class I molecules is
      impaired because of defective peptide translocation by transporters associated
      with antigen processing (TAP). Peptide transport is restored in HCMV mutants
      lacking US6. In contrast to the cytosolic herpes simplex virus protein ICP47, US6
      interacts with TAP inside the endoplasmic reticulum lumen, as shown by US6
      derivatives lacking the transmembrane and cytoplasmic domains and by the
      observation that US6 does not prevent peptides from binding to TAP. Thus, HCMV
      targets TAP for immune escape by a molecular mechanism different from that of
      herpes simplex virus.

PMID- 9175840
TI  - A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter.
AB  - Human cytomegalovirus inhibits peptide import into the endoplasmic reticulum (ER)
      by the MHC-encoded TAP peptide transporter. We identified the open reading frame
      US6 to mediate this effect. Expression of the 21 kDa US6 glycoprotein in human
      cytomegalovirus-infected cells correlates with the inhibition of peptide
      transport during infection. The subcellular localization of US6 is ER restricted
      and is identical with TAP. US6 protein is found in complexes with TAP1/2, MHC
      class I heavy chain, beta2-microglobulin, calnexin, calreticulin, and tapasin.
      TAP inhibition, however, is independent of the presence of class I heavy chain
      and tapasin. The results establish a new mechanism for viral immune escape and a
      novel role for ER-resident proteins to regulate TAP via its luminal face.

PMID- 9175842
TI  - Peptide-induced positive selection of TCR transgenic thymocytes in a coreceptor
      independent manner.
AB  - T cell receptor (TCR) transgenic thymocytes specific for the LCMV gp peptide are
      normally positively selected to the CD8 lineage. Transgenic thymocyte development
      was substantially reduced in the absence of these CD8 coreceptors. However,
      efficient positive selection was restored when TCR transgenic CD8-/- fetal thymic
      lobes were cultured with a peptide variant of the wild-type ligand. These mature
      thymocytes were functional, as shown by their ability to respond against strong
      peptide agonists. Additional experiments demonstrated that transgenic positive
      selection was peptide-specific. These results prove that CD8 does not possess
      essential signaling properties that are necessary for T cell development. In
      addition, the unilateral commitment of transgenic thymocytes to mature CD4
      TCR(hi) T cells expressing intracellular perforin suggests that there must be
      some instructive component to CD4 down-regulation and lineage commitment during
      thymocyte selection.

PMID- 9175841
TI  - CD8 lineage commitment in the absence of CD8.
AB  - The absence of cytotoxic T lymphocyte activity and the failure of MHC class I
      restricted T cell receptor (TCR) transgenic thymocytes to mature in CD8alpha
      deficient mice suggest that CD8 may be essential for CD8 lineage commitment. We
      report that variants of the antigenic peptide that delete TCR transgenic
      thymocytes from CD8 wild-type but not CD8alpha-deficient mice can restore
      positive selection of CD8 lineage cells in the absence of CD8. The positively
      selected cells down-regulate CD4, up-regulate TCR, respond to the antigenic
      peptide, and express CD8beta mRNA. Interestingly, there was no enhanced selection
      of CD4+ T cells, implying that the TCR-MHC interaction, even in the absence of
      CD8, provided instructive signaling for commitment to the CD8 lineage. Our
      results are discussed in terms of recent models of T cell lineage commitment.

PMID- 9175843
TI  - Apoptosis-mediated immunotoxicity of polychlorinated biphenyls (PCBs) in murine
      splenocytes.
AB  - Polychlorinated biphenyls (PCBs) exhibited immunotoxicity on antibody forming
      response to T-dependent antigen of sheep red blood cells, primary activation of T
      cells by mixed lymphocyte response, and lymphocyte proliferation induced by
      various mitogens. These immunosuppressions were related with the loss of
      lymphocyte viability which was determined by the propidium iodide method, and
      this death was proven to be linked with apoptosis which showed DNA fragmentation
      detected by the diphenylamine method and agarose gel electrophoresis. The degree
      of DNA fragmentation was increased in a dose- and time-dependent manner in PCB
      treated splenocytes. In conclusion, it was assumed that apoptosis was
      attributable to the immunotoxicity of PCBs in murine splenocytes.

PMID- 9175844
TI  - Cadmium perturbs calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells; a
      possible role for protein kinase C.
AB  - The mechanism of the toxic effects of Cd2+ on bone cell function is not
      completely understood at this time. This study was designed to characterize the
      effect of Cd2+ on Ca2+ metabolism in ROS 17/2.8 cells. Cells were labeled with
      (45)Ca (1.87 mM Ca) for 20 h in the presence of 0.01, 0.1, or 1.0 microM Cd2+ and
      kinetic parameters were determined from (45)Ca efflux curves. Three kinetic
      compartments described the intracellular metabolism of (45)Ca. Cd2+ (0.01 microM)
      caused an approximate 9 x increase in Ca2+ flux across the plasma membrane and a
      decrease in the most rapidly exchanging intracellular Ca2+ compartment (S1).
      However, there was no change in total cell Ca2+, indicating an increased cycling
      of Ca2+ across the plasma membrane. Flux between S1 and the intermediate Ca2+
      compartment (S2) was also increased and S2 increased significantly. All Cd2+
      induced changes in Ca2+ homeostasis were obliterated by concurrent treatment with
      0.1 microM calphostin C (CC), a potent protein kinase C (PKC) inhibitor. This
      data suggests that Cd2+ perturbs Ca2+ metabolism via a PKC dependent process.

PMID- 9175845
TI  - A highly toxic PCB produces unusual changes in the fatty acid composition of rat
      liver.
AB  - The changes in lipid metabolism produced by a coplanar PCB were studied in rats.
      Male Wistar rats were given a single intraperitoneal injection of 3,3',4,4',5
      pentachlorobiphenyl at a dose of 25 mg/kg. After 5 days of administration, total
      hepatic lipids were treated with 1 M KOH in methanol at 75 degrees C and the
      liberated fatty acids were analyzed by HPLC after conversion to fluorescent
      derivatives. In comparison with free-fed and pair-fed control groups, the
      proportion of arachidonic acid in the PenCB-treated rats was reduced by about
      50%, while oleic and linoleic acids increased significantly. We also examined the
      individual glycerophospholipids, separated by TLC, to see if they were affected
      by alteration in the fatty acid composition of the whole liver. In all
      glycerophospholipids, the proportion of arachidonic acid was reduced
      significantly to the same degree while linoleic acid increased. Changes in the
      activity of desaturase isozymes have been postulated to explain this unusual
      lipid metabolism following administration of a toxic PCB and this may contribute
      to its toxicity.

PMID- 9175846
TI  - Ochratoxin A in human sera in the area with endemic nephropathy in Croatia.
AB  - Ochratoxin A (OA) is nephrotoxic fungal metabolite (mycotoxin) occurring in
      foodstuffs. The compound is causally associated with mycotoxin porcine
      nephropathy, a disease comparable with a human kidney disease called endemic
      nephropathy (EN). In this paper we presented results obtained over a 10-year
      period in the hyperendemic village Kaniza, and in control villages where no
      clinical cases of nephropathy had been found. In the hyperendemic village Kaniza
      and non-endemic villages the incidence of OA in human blood was up to 4.5% (range
      2-50 ng/ml) and up to 2.4% (range 2-10 ng/ml), respectively. Almost all samples
      of food and feed, collected randomly in the hyperendemic village were found to
      contain OA. Considering marked exposure to OA in Kaniza, it was assumed that
      incidence of EN in this population could be related to OA contamination of food
      and feed.

PMID- 9175847
TI  - Effects of zinc and copper on cadmium uptake by brush border membrane vesicles.
AB  - The effects of essential metals, zinc (Zn) and copper (Cu), on cadmium (Cd)
      uptake were investigated in brush border membrane vesicles (BBMV) isolated from
      the rat renal cortex and LLC-PK1 cells. BBMV were incubated with Cd in the
      presence or absence of Zn or Cu, and then washed with a chelating agent, EGTA, to
      remove Cd bound to the outer surface of BBMV. Co-incubation with Zn or Cu
      decreased Cd accumulation in these BBMV in a concentration-dependent manner.
      Kinetic analysis of the initial accumulation of Cd suggested that Cd is taken up
      into rat BBMV via an unsaturable component and a saturable component (K(m) = 13.8
      microM, V(max) = 1.44 nmol/mg protein/min), and co-incubation with Zn
      significantly increased the K(m) of the saturable component without affecting the
      V(max), whereas Cu significantly increased the K(m)-value and decreased the
      V(max)-value. Increasing the osmolarity of the incubation medium slightly
      decreased Cd accumulation in the absence of Zn or Cu, whereas it did not decrease
      Cd accumulation in the presence of these metals. These results suggest the
      possibility that, in addition to passive diffusion, Cd is also taken up from the
      renal brush border membrane via carrier-mediated mechanisms that are inhibited by
      Zn competitively and by Cu non-competitively. Furthermore, these results suggest
      that: (1) Cd binds externally and internally to BBMV, (2) little Cd is
      transported into the intravesicular space, and (3) both Zn and Cu decrease the
      binding and transport of Cd.

PMID- 9175848
TI  - Comparison of ribosome-inactivating proteins in the induction of apoptosis.
AB  - The aim of this study was to evaluate the ability of verocytotoxin-1 (VT1), VT1 B
      chain alone, ricin and a hybrid toxin (RASTA2) consisting of ricin A chain linked
      to VT1 B chain to inhibit protein synthesis and to induce apoptosis. The lethal
      effects of the toxins were compared using vero cells (originating from green
      African monkey kidney tissue). As previously described cell death occurred
      through apoptosis which was quantified using the diphenylamine assay. DNA
      fragmentation was seen with VT1 at 10 pg/ml but there was no effect with B chain
      alone. Fragmentation with ricin was seen at 10 ng/ml and with RASTA2 at 1 ng/ml.
      Protein synthesis inhibition was measured by [(35)S]methionine incorporation. VT1
      had an IC50 of 0.0024 ng/ml, B chain alone was ineffective at inhibiting protein
      synthesis. Ricin had an IC50 of 0.39 ng/ml and RASTA2 of 1.7 ng/ml. In vero cells
      the B chain of these toxins does not participate in cell killing.

PMID- 9175849
TI  - Dietary alpha-tocopherol prevents dehydroepiandrosterone-induced lipid
      peroxidation in rat liver microsomes and mitochondria.
AB  - Dehydroepiandrosterone (DHEA), an adrenal steroid, causes lipid peroxidation in
      rat liver microsomes and mitochondria and induces hepatocarcinogenesis. It was
      investigated whether alpha-tocopherol, a naturally occurring free radical chain
      terminator, could decrease lipid peroxidation. When DHEA-free diet supplemented
      with increasing concentrations of alpha-tocopherol (25, 50, 100, 200, 400 and
      1000 mg/kg diet) was fed to rats for 7 days, a marked lipid peroxidation
      (measured as thiobarbituric acid reactive substances formation) was observed at
      concentrations 25 and 50 mg/kg in liver microsomes and mitochondria isolated from
      these animals. Lipid peroxidation was significantly reduced at concentrations >
      or = 100 mg/kg. When DHEA (500 mg/kg diet) was fed to rats simultaneously with
      increasing concentrations of alpha-tocopherol, strong lipid peroxidation was
      observed at alpha-tocopherol concentrations < or = 200 mg/kg diet. However,
      microsomes and mitochondria isolated from livers of rats fed alpha-tocopherol at
      doses of 400 and 1000 mg/kg diet produced only negligible amounts of
      thiobarbituric acid reactive substances. The data show that high concentrations
      of alpha-tocopherol in the diet decrease DHEA-induced microsomal and
      mitochondrial lipid peroxidation. Our results support the concept that alpha
      tocopherol can protect against DHEA-induced lipid peroxidation and consequently
      against steroid-induced liver cell damage and, perhaps, also tumour development.

PMID- 9175850
TI  - Thirteen-week subchronic toxicity study of thiamphenicol in F344 rats.
AB  - A 13-week subchronic toxicity study of thiamphenicol (TAP) was performed in F344
      rats. The minimum lethal dose was estimated to be greater than 10 g/kg body
      weight, when a single dose of 4-10 g/kg of TAP was given orally. In the
      subchronic toxicity study, groups of 12 F344 rats of each sex were given
      solutions containing 0 (control), 125, 250 and 500 ppm of TAP as their drinking
      water ad libitum for 13 weeks. Body weight gain was significantly suppressed in
      both sexes of the 250 and 500 ppm groups. Slight suppression of erythropoiesis
      was observed in the highest-dose group along with slightly reduced
      spermatogenesis in the testes of the males. In addition, spermatogranulomas were
      found in the epididymis of both middle- and highest-dose groups. The no observed
      adverse effect level (NOAEL) was concluded to be 125 ppm (daily doses of 9.0
      mg/kg in males and 11.6 mg/kg in females). From the above described results,
      doses of 250 and 125 ppm were selected as appropriate for a 2-year
      carcinogenicity study.

PMID- 9175851
TI  - Reproducibility of urinary beta 2-microglobulin and cadmium excretion among
      residents in a cadmium-polluted area during a 3-year period.
AB  - To assess the measurement error by using single exposure measurement in
      epidemiologic studies, reproducibility of urinary beta 2-microglobulin and
      cadmium excretion was evaluated among persons exposed to environmental cadmium.
      We measured urinary beta 2-microglobulin concentrations in 47 subjects four times
      and urinary cadmium concentrations in 48 subjects twice, during a 3-year period.
      Between-person and within-person variance components of these variables were
      estimated using a random-effects one-way analysis of variance model. The
      intraclass correlation coefficient (ICC) for urinary beta 2-microglobulin
      concentration, when expressed as microg/g creatinine and microg/l, was 0.92 and
      0.89, respectively. The ICC for standardized urinary cadmium concentration
      (expressed as microg/g creatinine) was 0.81, while it decreased to 0.33 without
      standardization. The findings suggest that single measurement of urinary beta 2
      microglobulin and cadmium, when expressed as a function of creatinine, can
      reliably estimate average levels over at least a 3-year period. Standardization
      of concentration using urinary creatinine improved reproducibility especially for
      urinary cadmium excretion.

PMID- 9175853
TI  - Reply to Professors Purchase and Gelbke.

PMID- 9175852
TI  - Uptake of nickel into the brain via olfactory neurons in rats.
AB  - Intranasal instillation of nickel ([63]Ni2+) in rats resulted in an uptake of the
      metal in the olfactory epithelium and a migration along primary olfactory neurons
      to the glomeruli of the olfactory bulb. The metal was then seen to pass to the
      interior of the bulb and further to the olfactory peduncle, the olfactory
      tubercle and the rostral parts of the prepiriform, frontal and cingulate
      corticis. These results indicate that (63)Ni2+ slowly passes to secondary and
      tertiary olfactory neurons. Intraperitoneal injection of (63)Ni2+ resulted in a
      low uptake in the brain, without preferential labelling of the olfactory
      pathways. Inhalation of nickel compounds can impair the olfactory system. An
      uptake of nickel in the olfactory neurons may underly these lesions.

PMID- 9175854
TI  - Effects on mRNA degradation by Escherichia coli transcription termination factor
      Rho and pBR322 copy number control protein Rop.
AB  - Mutants in Escherichia coli transcription termination factor Rho, termed
      rho(nusD), were previously isolated based on their ability to block the growth of
      bacteriophage T4. Here we show that rho(nusD) strains have decreased average half
      lives for bulk cellular mRNA. Decreased E. coli message lifetimes could be
      because of increased ribonuclease activity in the rho mutant cells: if a Rho
      dependent terminator precedes a ribonuclease gene, weaker termination in the rho
      mutants could lead to nuclease overexpression. However, inactivation of
      ribonuclease genes in rho026 cells did not relieve the defective phage growth.
      Unexpectedly, expression of the pBR322 Rop protein, a structure-specific,
      sequence-independent RNA-binding protein, in rho(nusD) cells restored the ability
      of T4 to grow and prolonged cellular message half-life in both the wild-type and
      the rho026 mutant. These results suggest that it is the RNA-binding ability of
      Rho rather than its transcription termination function that is important for the
      inhibition of bacteriophage growth and the shorter bulk mRNA lifetime. We propose
      that altered interaction of the mutant Rho with mRNA could make the RNA more
      susceptible to degradation. The inability of the RNA-binding proteins SrmB and
      DeaD to reverse the rho mutant phenotype when each is overexpressed implies that
      the required RNA interactions are specific. The results show novel roles for Rho
      and Rop in mRNA stability.

PMID- 9175855
TI  - Only one nucleotide insertion to the long variable arm confers an efficient
      serine acceptor activity upon Saccharomyces cerevisiae tRNA(Leu) in vitro.
AB  - Several tRNA species have a long variable arm composed of over ten nucleotides,
      which are relevant to those specific to serine, leucine and tyrosine in
      prokaryotes, while there are only serine and leucine-specific tRNAs in
      eukaryotes. To clarify the evolutionary aspects of the identity determination
      mechanism of these tRNAs, the tRNA(Ser) recognition in Saccharomyces cerevisiae
      was studied. Unmodified tRNA(Leu) transcript had serylation ability of low
      efficiency, but native tRNA(Leu) did not, indicating that some modification of
      tRNA(Leu) serves as a negative identity determinant for seryl-tRNA synthetase.
      Changing the discriminator base did not seriously affect the serine accepting
      efficiency. The tRNA(Leu) transcript possessing the variable arm of tRNA(Ser) was
      efficiently aminoacylated with serine. Eventually, it was found that only one
      nucleotide insertion to the variable arm of tRNA(Leu) was sufficient to confer an
      efficient serine accepting activity. The mode of serine tRNA recognition is
      similar to that in Escherichia coli in that the end of the long variable arm, but
      not the anticodon or discriminator base, is important. However, S. cerevisiae
      seryl-tRNA synthetase adopts a substantially different mechanism for rejection of
      tRNA(Leu) from that of its E. coli counterpart.

PMID- 9175856
TI  - GroE modulates kinetic partitioning of folding intermediates between alternative
      states to maximize the yield of biologically active protein.
AB  - The central issue of chaperone function is the mechanism whereby partitioning of
      folding polypeptides along the productive pathway may be maximized, while non
      productive folding pathways are minimized. We have found that the GroE chaperone
      is capable of accelerating the rate of the productive pathway of bacterial
      luciferase alphabeta heterodimer formation. At intermediate temperatures at which
      the productive pathway and non-productive pathways leading to dimerization
      incompetent monomeric forms of the subunits coexist, GroE enhances the yield of
      native enzyme while minimizing the yield of misfolded protein. These results
      suggest that GroE releases the subunits in forms capable of achieving the native
      structure faster than the forms initially bound by the chaperone. At higher
      temperatures, at which the native enzyme is stable but the dimerization reaction
      is diminished, GroE is unable to force the productive folding reaction to occur.
      However, the chaperone decreases the rate of formation of the heterodimerization
      incompetent species, thereby enhancing the final yield of active enzyme when the
      temperature is reduced to the permissive range. Our results suggest a mechanism
      by which the chaperone functions to maximize the yield of the biologically active
      form of the protein while maintaining or even accelerating the essential rapid
      kinetics of folding reactions.

PMID- 9175857
TI  - Molecular and immunological analysis of an ABC transporter complex required for
      cytochrome c biogenesis.
AB  - The helABC genes are predicted to encode an ATP-binding cassette (ABC)
      transporter necessary for heme export for ligation in bacterial cytochrome c
      biogenesis. The recent discoveries of homologs of the helB and helC genes in
      plant mitochondrial genomes suggest this is a highly conserved transporter in
      prokaryotes and some eukaryotes with the HelB and HelC proteins comprising the
      transmembrane components. Molecular genetic analysis in the Gram-negative
      bacterium Rhodobacter capsulatus was used to show that the helABC and helDX genes
      are part of an operon linked to the secDF genes. To facilitate analysis of this
      transporter, strains with non-polar deletions in each gene, epitope and reporter
      tagged HelABCD proteins, and antisera specific to the HelA and HelX proteins were
      generated. We directly demonstrate that this transporter is present in the
      cytoplasmic membrane as an HelABCD complex. The HelB and HelC but not HelD
      proteins are necessary for the binding and stability of the HelA protein, the
      cytoplasmic subunit containing the ATP-binding region. In addition we show that
      the HelA protein co-immunoprecipitates with either the HelC or HelD proteins.
      Thus, the HelABCD heme export complex is distinguished by the presence of four
      membrane-associated subunits and represents a unique subfamily of ABC
      transporters.

PMID- 9175858
TI  - A crystallographic comparison between mutated glyceraldehyde-3-phosphate
      dehydrogenases from Bacillus stearothermophilus complexed with either NAD+ or
      NADP+.
AB  - Mutations have been introduced in the cytosolic glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) from Bacillus stearothermophilus in order to convert its
      cofactor selectivity from a specificity towards NAD into a preference for NADP.
      In the B-S mutant, five mutations (L33T, T34G, D35G, L187A, P188S) were selected
      on the basis of a sequence alignment with NADP-dependent chloroplastic GAPDHs. In
      the D32G-S mutant, two of the five mutations mentioned above (L187A, P188S) have
      been used in combination with another one designed from electrostatic
      considerations (D32G). Both mutants exhibit a dual-cofactor selectivity at the
      advantage of either NAD (B-S) or NADP (D32G-S). In order to analyse the cofactor
      binding site plasticity at the molecular level, crystal structures of these
      mutants have been solved, when complexed with either NAD+ (D32G-Sn, resolution
      2.5 A, R = 13.9%; B-Sn, 2.45 A, 19.3%) or NADP+ (D32G-Sp, 2.2 A, 19.2%; B-Sp, 2.5
      A, 14.4%). The four refined models are very similar to that of the wild-type
      GAPDH and as expected resemble more closely the holo form than the apo form. In
      the B-S mutant, the wild-type low affinity for NADP+ seems to be essentially
      retained because of repulsive electrostatic contacts between the extra 2'
      phosphate and the unchanged carboxylate group of residue D32. Such an
      antideterminant effect is not well compensated by putative attractive
      interactions which had been expected to arise from the newly-introduced side
      chains. In this mutant, recognition of NAD+ is slightly affected with respect to
      that known on the wild-type, because mutations only weakly destabilize hydrogen
      bonds and van der Waals contacts originally present in the natural enzyme. Thus,
      the B-S mutant does not mimic efficiently the chloroplastic GAPDHs, and long
      range and/or second-layer effects, not easily predictable from visual inspection
      of three-dimensional structures, need to be taken into account for designing a
      true "chloroplastic-like" mutant of cytosolic GAPDH. In the case of the D32G-S
      mutant, the dissociation constants for NAD+ and NADP+ are practically reversed
      with respect to those of the wild-type. The strong alteration of the affinity for
      NAD+ obviously proceeds from the suppression of the two wild-type hydrogen bonds
      between the adenosine 2'- and 3'-hydroxyl positions and the D32 carboxylate
      group. As expected, the efficient recognition of NADP+ is partly promoted by the
      removal of intra-subunit electrostatic repulsion (D32G) and inter-subunit steric
      hindrance (L187A, P188S). Another interesting feature of the reshaped NADP+
      binding site is provided by the local stabilization of the extra 2'-phosphate
      which forms a hydrogen bond with the side-chain hydroxyl group of the newly
      introduced S188. When compared to the presently known natural NADP-binding
      clefts, this result clearly demonstrates that an absolute need for a salt-bridge
      involving the 2'-phosphate is not required to switch the cofactor selectivity
      from NAD to NADP. In fact, as it is the case in this mutant, only a moderately
      polar hydrogen bond can be sufficient to make the extra 2'-phosphate of NADP+
      well recognized by a protein environment.

PMID- 9175859
TI  - Non-native local interactions in protein folding and stability: introducing a
      helical tendency in the all beta-sheet alpha-spectrin SH3 domain.
AB  - The relative importance of secondary structure interactions versus tertiary
      interactions for stabilising and guiding the folding process is a matter for
      discussion. Phenomenological models of protein folding assign an important role
      to local contacts in protein folding and stability. On the other hand, simplistic
      lattice simulations find that secondary structure is mainly the product of
      protein compaction and that optimisation of folding speed seems to require small
      contributions of local contacts to the stability of the folded state. To examine
      the extent to which secondary structure propensities influence protein folding
      and stability, we have designed mutations that introduce a strong non-native
      helical propensity in the first 19 residues of the alpha-spectrin SH3 domain. The
      mutant proteins have the same three-dimensional structure as the wild-type, but
      they are less stable and have less co-operative folding transitions. There seems
      to be a relationship between the non-native helical propensity and the compaction
      of the denatured state. This suggests that in the denatured ensemble under native
      conditions there is a significant proportion of compact structures with non
      native secondary structures. Our results demonstrate that non-local interactions
      can overcome strong non-native secondary structure propensities and, more
      important, that optimisation of folding speed and co-operativity requires the
      latter to be relatively small.

PMID- 9175860
TI  - Atomic resolution (1.0 A) crystal structure of Fusarium solani cutinase:
      stereochemical analysis.
AB  - X-ray data have been recorded to 1.0 A resolution from a crystal of Fusarium
      solani cutinase using synchrotron radiation and an imaging-plate scanner. The
      anisotropic treatment of thermal motion led to a fivefold increase in accuracy
      and to a considerable quality improvement in the electron density maps with
      respect to an intermediate isotropic model. The final model has an R-factor of
      9.4%, with a mean coordinate error of 0.021 A, as estimated from inversion of the
      least-squares matrix. The availability of an accurate structure at atomic
      resolution and of meaningful estimates of the errors in its atomic parameters,
      allowed an extensive analysis of several stereochemical parameters, such as
      peptide planarity, main-chain and some side-chain bond distances. The hydrogen
      atoms could be clearly identified in the electron density, thus providing
      unambiguous evidence on the protonation state of the catalytic histidine residue.
      The atomic resolution revealed an appreciable extent of flexibility in the
      cutinase active site, which might be correlated with a possible adaptation to
      different substrates. The anisotropic treatment of thermal factors provided
      insights into the anisotropic nature of motions. The analysis of these motions in
      the two loops delimiting the catalytic crevice pointed out a "breath-like"
      movement in the substrate binding region of cutinase.

PMID- 9175861
TI  - Mitochondrial fatty acid synthesis: a relic of endosymbiontic origin and a
      specialized means for respiration.
AB  - Genes that encode mitochondrial homologues to the bacterial enzymes of fatty acid
      synthesis were found in various eukaryotic species. Inactivation of these genes
      leads to a disturbed mitochondrial respiration and an increase in mitochondrial
      lysophospholipids. We postulate that there is a mitochondrial biosynthetic system
      providing fatty acids for phospholipid repair. The mitochondrial acyl carrier
      protein may also play another role, supporting the formation of the respiratory
      NADH:ubiquinone oxidoreductase.

PMID- 9175862
TI  - The L7/L12 ribosomal domain of the ribosome: structural and functional studies.
AB  - The L7/L12 protein forms a functionally important domain in the ribosome. This
      domain is involved in interaction with translation factors during protein
      biosynthesis. The tertiary and quaternary structure of the L7/L12 protein was
      established as a result of intensive studies in solution and in the ribosome. The
      conformational changes of L7/L12, the elongation factors Tu and G and other
      ribosomal proteins were traced by different experimental techniques. These
      changes occur upon interaction of the ribosome with the elongation factors and
      depend on GTP hydrolysis in accordance with the functional states of the
      ribosome.

PMID- 9175863
TI  - Interaction of the G-protein G11alpha with receptors and phosphoinositidase C:
      the contribution of G-protein palmitoylation and membrane association.
AB  - Wild-type and palmitoylation defective mutants of the murine G protein G11alpha
      were transfected into HEK293 cells. Wild-type G11alpha was membrane associated,
      Cys9Ser Cys10Ser G11alpha was present in the soluble fraction whilst both Cys9Ser
      G11alpha and Cys10Ser G11alpha were distributed between the fractions. Expression
      of the rat TRH receptor resulted in agonist stimulation of inositol phosphate
      accumulation. The degree of stimulation produced by TRH following co-transfection
      of the palmitoylation-resistant forms of G11alpha compared to the wild-type
      protein correlated with the amount of membrane-associated G protein.

PMID- 9175864
TI  - Cholinesterases from the common oyster (Crassostrea gigas). Evidence for the
      presence of a soluble acetylcholinesterase insensitive to organophosphate and
      carbamate inhibitors.
AB  - Marine bivalves such as oysters and mussels are widely used as bioindicators of
      contamination in the monitoring of pollutant effects. As filter feeders, these
      species are known to be good general indicators of chemical contamination.
      However, the efficient use of decreased acetylcholinesterase activity in the
      oyster as a biomarker of exposure to neurotoxic compounds requires a definition
      of the different types of cholinesterases coexisting in this mollusk. This study
      reports the partial purification, separation and characterization of two
      cholinesterases extracted from the oyster Crassostrea gigas. Differences in
      apparent molecular weight, type of glycosylation and hydrophobicity, and
      sensitivity to inhibitors suggest that they are encoded by two different genes.
      'A' cholinesterase (apparent molecular weight 200 kDa) is anchored to the
      membrane via a glycolipid, is not glycosylated but sensitive to organophosphate
      and carbamate inhibitors. 'B' cholinesterase (molecular weight 330 kDa) is
      hydrophilic, glycosylated and highly resistant to organophosphate and carbamate
      inhibitors. The kinetic properties of these two cholinesterases were compared
      with those of other invertebrate cholinesterases. The presence of a
      cholinesterase insensitive to insecticides suggests that a significant
      improvement in the use of oyster cholinesterases as biomarkers of pollutant
      effects could be achieved by simple separation of the two forms.

PMID- 9175865
TI  - Increased glucose transport in ras-transformed fibroblasts: a possible role for N
      glycosylation of GLUT1.
AB  - 2-Deoxyglucose uptake was enhanced in ts371 KiMuSV-NRK cells when growing at the
      permissive temperature to allow the expression of a transforming p21 ras protein.
      This change is due to a decrease in the K(m) by approximately 2.5-fold without
      affecting the V(max) of the transporter. The amount of the GLUT1 glucose
      transporter dit not increase as deduced from immunoblot experiments on total
      membranes. Nevertheless, ras-transformed GLUT1 displays a higher molecular mass
      due to an increased N-glycosylation of the protein. Experiments made in
      tunicamycin-treated cells indicates that a higher glycosylation is responsible
      for the increase in 2-deoxyglucose uptake in ras-transformed cells.

PMID- 9175866
TI  - Restoration of lectin activity to a non-glycosylated ricin B chain mutant by the
      introduction of a novel N-glycosylation site.
AB  - Ricin B chain (RTB) is an N-glycosylated, galactose-specific lectin. Removal of
      the two native N-glycosylation sites at Asn95 and Asn135 by site-directed
      mutagenesis generated a recombinant protein devoid of lectin activity. Two novel
      N-glycosylation sites were introduced into RTB at Asn42 and Asn123, either singly
      or in combination. Microinjection of pre-RTB transcripts into Xenopus oocytes
      showed that these novel sites became glycosylated in vivo. The single
      oligosaccharide site chain at Asn42 restored lectin activity to RTB, whereas
      glycosylation at Asn123 or simultaneous glycosylation at Asn42 and Asn123 failed
      to do so.

PMID- 9175867
TI  - Cytotoxic activity of ribonucleolytic toxin restrictocin-based chimeric toxins
      targeted to epidermal growth factor receptor.
AB  - Targeted toxins represent a new approach to specific cytocidal therapy. The
      ribonucleolytic protein toxin restrictocin is a potent protein synthesis
      inhibitor produced by the fungus Aspergillus restrictus. In the present study we
      have constructed two restrictocin based chimeric toxins where human transforming
      growth factor alpha (TGF alpha) has been used as a ligand. TGF alpha is a single
      chain polypeptide, which binds to epidermal growth factor receptor (EGFR) and
      causes proliferation in a large number of cancers. The ligand has been separately
      fused either at the amino terminus or carboxyl terminus of restrictocin, giving
      rise to TGF alpha-restrictocin and restrictocin-TGF alpha respectively. The
      fusion proteins were overexpressed in Escherichia coli and purified from
      inclusion bodies by a denaturation-renaturation protocol. Both the chimeric
      toxins actively inhibited eukaryotic protein synthesis in a cell free in vitro
      translation assay system. These chimeric toxins selectively killed human
      epidermal growth factor receptor positive target cells in culture. Among the two
      proteins, restrictocin-TGF alpha was more active than TGF alpha-restrictocin on
      all the cell lines studied.

PMID- 9175868
TI  - Studies of high thermostability and peroxidase activity of recombinant antibody L
      chain-porphyrin Fe(III) complex.
AB  - A complex of an independent L chain from anti-mesotetrakis (4-carboxyphenyl)
      porphyrin (TCPP) monoclonal antibody 13-1 and TCPP Fe(III) was designated as L
      zyme and shown to exhibit high peroxidase activity and high optimal reaction
      temperature (90 degrees C). Heat denaturation study and circular dichroism (CD)
      spectra analysis suggested that refolded structure of 13-1 L chain exhibited
      significantly reduced inactivation rate after heat treatment. The secondary
      structure of 13-1 L chain changed slightly by the encapsulation of TCPP Fe(III)
      and the complex was found to be less thermostable than the L chain alone.
      Furthermore, by characterization of truncated forms of the L chain, it was
      revealed that the hydrophobic region (115-146) and hydrophilic region (147-189)
      in CL are important for thermostability and activity, respectively. Tertiary
      structure of L-zyme was predicted by AbM. Comparison of residues of L-zyme with
      those in the active centre of known structure of the peroxidase from Arthromyces
      ramosus (ARP) indicated that His38(CDR1), His94(CDR3), Arg96(CDR3) of L-zyme are
      important residues for peroxidase activity. Moreover, the steric arrangements of
      these residues in both L-zyme and ARP are similar, respectively. Distance between
      proximal His and distal His in L-zyme is 9.09 A, whereas that of ARP is 7.8 A.

PMID- 9175869
TI  - Similarity of bacteriorhodopsin structural changes triggered by chromophore
      removal and light-driven proton transport.
AB  - Bacteriorhodopsin (bR) is the light-driven proton pump found in the purple
      membrane of Halobacterium salinarium. A series of conformational changes occur
      during the bR photocycle which involve alterations in buried-helical structure as
      well as in the protonation state of Asp residues which are part of the proton
      transport pathway. Here we report evidence that similar conformational changes
      occur upon removal of the retinylidene chromophore of bacteriorhodopsin to form
      the apoprotein bacterioopsin (bO). This suggests a simple ligand-binding model of
      proton transport in bacteriorhodopsin which may have relevance to other transport
      and signal transducing membrane proteins including the visual photoreceptor
      rhodopsin.

PMID- 9175870
TI  - Altered cleavage site preference of a proteolytic antibody light chain induced by
      denaturation.
AB  - A recombinant antibody light chain (L chain) maintained under non-denaturing
      conditions displayed preferential cleavage of synthetic peptides conjugated to
      methylcoumarinamide (MCA) on the C-terminal side of Arg and Lys residues. The
      same L chain renatured from a denaturing solvent (guanidine hydrochloride)
      acquired the capability of cleaving Tyr-MCA and Leu-MCA bonds, and its ability to
      cleave MCA linked to basic residues was decreased. The altered cleavage
      preference was accompanied by a conformational transition in the protein, evident
      from the fluorescence emission spectra. These observations suggest the
      feasibility of redirecting the cleavage specificity via alterations in the
      conformation of proteolytic antibody combining sites.

PMID- 9175871
TI  - Interaction between cellohexaose and cellulose binding domains from Trichoderma
      reesei cellulases.
AB  - Most Trichoderma reesei cellulases consist of a catalytic and a cellulose binding
      domain (CBD) joined by a linker. We have used cellohexaose as a model compound
      for the glucose chain to investigate the interaction between the soluble enzyme
      and cellulose. The binding of cellohexaose to family I CBDs was studied by NMR
      spectroscopy. CBDs cause line broadening effects and decreasing T2 relaxation
      times for certain cellohexaose resonances, whereas there are no effects in the
      presence of a mutant which binds weakly to cellulose. Yet it remains uncertain
      how well the soluble cellooligosaccharide mimics the binding of CBD to the
      cellulose.

PMID- 9175872
TI  - Imidazolone, a novel advanced glycation end product, is present at high levels in
      kidneys of rats with streptozotocin-induced diabetes.
AB  - We produced a monoclonal antibody to imidazolones A and B, novel advanced
      glycation end products formed from the reaction of 3-deoxyglucosone (3-DG) with
      the guanidino group of arginine. Liquid chromatography/mass spectrometry
      demonstrated that the formation of imidazolone A by incubating 3-DG with arginine
      is very rapid, reaching a maximum concentration within 24 h, but the formation of
      imidazolone B is very slow and low in quantity even after 2 weeks. Thus, at
      physiological conditions the formation of imidazolone A is dominant, while that
      of imidazolone B is negligible. Immunochemistry demonstrated that the imidazolone
      content in the kidneys of streptozotocin-induced diabetic rats was significantly
      higher than in the control rats. Serum levels of 3-DG in the diabetic rats were
      also significantly higher than in control rats. 3-DG attacks the arginine
      residues of the tissue proteins, producing imidazolone at high levels in the
      kidneys affected by diabetic nephropathy.

PMID- 9175873
TI  - A novel model for the first nucleotide binding domain of the cystic fibrosis
      transmembrane conductance regulator.
AB  - Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. The most frequent mutation is the deletion of
      F508 in the first nucleotide binding fold (NBF1). It induces a perturbation in
      the folding of NBF1, which impedes posttranslational maturation of CFTR.
      Determination of the three-dimensional structure of NBF1 would help to understand
      this defect. We present a novel model for NBF1 built from the crystal structure
      of bovine mitochondrial F1-ATPase protein. This model gives a reasonable
      interpretation of the effect of mutations on the maturation of the protein and,
      in agreement with the CD data, leads to reconsideration of the limits of NBF1
      within CFTR.

PMID- 9175874
TI  - Low-conductance high selective inositol (1,4,5)-trisphosphate activated Ca2+
      channels in plasma membrane of A431 carcinoma cells.
AB  - In many cells, activation of receptors coupled to PIP2 turnover results in Ca2+
      release from the intracellular stores accompanied by Ca2+ influx across the PM.
      It is not well established yet whether Ca2+ influx is activated by IP3 or by an
      unknown signal generated upon Ca2+ store depletion. We report here a single
      channel study of low-conductance IP3-activated channels of very high selectivity
      for Ca2+ in the PM of A431 carcinoma cells. The channels are strongly potential
      dependent and sensitive to [Ca2+]i within the physiological range. The data
      obtained argues for IP3 acting directly on plasma membrane Ca2+ channels.

PMID- 9175875
TI  - 'Green mice' as a source of ubiquitous green cells.
AB  - The green fluorescent protein (GFP) is responsible for the green bioluminescence
      of the jellyfish Aequorea victoria. Many classes of GFP mutants exist that
      display modified fluorescence spectra and an increased extinction coefficient. We
      produced transgenic mouse lines with an 'enhanced' GFP (EGFP) cDNA under the
      control of a chicken beta-actin promoter and cytomegalovirus enhancer. All of the
      tissues from these transgenic lines, with the exception of erythrocytes and hair,
      were green under excitation light. The fluorescent nature of the cells from these
      transgenic mouse lines would facilitate their use in many kinds of cell
      transplantation experiments.

PMID- 9175877
TI  - Periodicity in recA protein-DNA complexes.
AB  - The reaction of guanine residues with dimethylsulfate was studied for complexes
      of recA protein with fluorescent dye tagged double stranded oligonucleotides. The
      patterns of dimethylsulfate modification obtained demonstrate a similarity of DNA
      states in the complexes with recA protein formed as a result of recA promoted
      strand exchange and renaturation reactions. The guanine modification efficiency
      varies periodically as a function of the base position along the oligonucleotide
      axis, with a period of 3 nucleotides. This effect suggests that the arrangement
      of recA monomers along the oligonucleotide is strictly ordered, and the
      dimethylsulfate reactivity of a guanine residue depends on the site of its
      binding in a recA monomer.

PMID- 9175876
TI  - Functional interference between contacting amino acids of homeodomains.
AB  - In a protein, the function of an amino acid at some position depends on the amino
      acids at other positions. Here we demonstrate a functional interference between
      base-contacting amino acids (at positions 50 and 54) of homeodomains. When, in
      the context of Antennapedia or Goosecoid homeodomains, Lys50 is paired to Tyr54
      or Ala54 and Gln50 is paired to Met54, the resulting proteins efficiently
      discriminate among different DNA sequences. In contrast, in the presence of the
      pair Lys50-Met54, both homeodomains show a reduced capability to discriminate
      among different DNA sequences. Sequence selection experiments performed in the
      context of the Goosecoid homeodomain suggest that the presence of Met54 precludes
      the base-discriminating function of Lys50. These results may explain why the pair
      Lys50-Met54 is never found in natural homeodomains.

PMID- 9175878
TI  - Plasma membrane content of insulin-regulated glucose transporter in skeletal
      muscle of the male Otsuka Long-Evans Tokushima Fatty rat, a model of non-insulin
      dependent diabetes mellitus.
AB  - The male Otsuka Long-Evans Tokushima Fatty (OLETF) rat shows insulin resistance
      in skeletal muscle and visceral obesity. To obtain information on the mechanism
      of the insulin resistance in the diabetic rats, we examined the content of
      insulin-regulated glucose transporter (GLUT4) in skeletal muscles. The results
      indicate that the total content of the transporter is significantly decreased (P
      < 0.05) in muscles of the diabetic rats. Plasma membrane content of the GLUT4
      protein in muscles of the diabetic rats was increased in the basal state as
      compared to control rats. Hyperinsulinemic clamps increased GLUT4 levels in the
      plasma membrane of control rats but failed to do so in the diabetic rats. The
      distribution of GLUT4 in OLETF rat is reminiscent of the characteristics of human
      non-insulin-dependent diabetes mellitus.

PMID- 9175879
TI  - Recombinant human O6-alkylguanine-DNA alkyltransferase induces conformational
      change in bound DNA.
AB  - Circular dichroism, and steady-state and time-resolved fluorescence spectroscopy
      were used to compare the native recombinant human DNA repair protein O6
      alkylguanine-DNA alkyltransferase (AGT) with AGT bound to ds-DNA. Contrary to
      fluorescence, analysis of the far-UV CD spectra indicated a conformational change
      of AGT upon binding to DNA: its alpha-helical content is increased by
      approximately 12%. Analysis of near-UV CD spectra revealed that DNA was also
      affected, probably being separated into single strands locally.

PMID- 9175880
TI  - Demonstration that the BchH protein of Rhodobacter capsulatus activates S
      adenosyl-L-methionine:magnesium protoporphyrin IX methyltransferase.
AB  - The bchH gene of Rhodobacter capsulatus has been cloned into an expression strain
      of Escherichia coli. Following induction of expression of the BchH protein, it
      was found that the E. coli strain also accumulated porphyrins with the
      fluorescence properties of protoporphyrin and zinc protoporphyrin. It was also
      found that the soluble BchH protein increased the activity of S-adenosyl-L
      methionine:magnesium protoporphyrin IX methyltransferase, when mixed with
      membranes of an expression strain of E. coli into which the bchM gene (which
      encodes the methyltransferase) had been cloned, as well as membranes of a bchH
      mutant of R. capsulatus.

PMID- 9175881
TI  - Activation of MAP kinase cascade induced by human pancreatic phospholipase A2 in
      a human pancreatic cancer cell line.
AB  - We have found that the growth of human pancreatic cancer cells MIAPaCa-2, induced
      by human pancreatic phospholipase A2 group I (hPLA2-I), is mediated via its
      specific receptor but not via its catalytic property. The present study showed
      that the activation of mitogen-activated protein kinase (MAPK) cascade in MIAPaCa
      2 cells is induced by hPLA2-I: this digestive enzyme induced phosphorylation of
      MEK1/2, p44/42 MAPK and ATF-2, and the phosphorylation in the MAPK cascade was
      inhibited after the cells were pre-incubated with a selective inhibitor of MEK,
      PD98059. In addition, this inhibitor dose-dependently blocked the hPLA2-I-induced
      MIAPaCa-2 proliferation, suggesting that activation of the MAPK cascade is
      essential for the hPLA2-I-induced MIAPaCa-2 proliferation.

PMID- 9175882
TI  - Direct determination of the chemical composition of acetylcholinesterase
      phosphonylation products utilizing electrospray-ionization mass spectrometry.
AB  - While non-reactivability of cholinesterases from their phosphyl conjugates
      (aging) is attributed to an unimolecular process involving loss of alkyl group
      from the phosphyl moiety, no conclusive evidence is available that this is the
      only reaction path and involvement of other post-inhibitory processes cannot be
      ruled out. To address this issue, molecular masses of the bacterially expressed
      recombinant human acetylcholinesterase and of its conjugates with a homologous
      series of alkyl methylphosphonofluoridates, were measured by electrospray
      ionization mass spectrometry (ESI-MS). The measured mass of the free enzyme was
      64,700 Da (calculated 64,695 Da) and those of the methylphosphono-HuAChE adducts,
      bearing isopropyl, isobutyl, 1,2-dimethylpropyl and 1,2,2-trimethylpropyl
      substituents, were 64,820, 64,840, 64,852 and 64,860 Da, respectively. These
      values reflect both the addition of the phosphonyl moiety and the gradual mass
      increase due to branching of the alkoxy substituent. The composition of these
      adducts change with time to yield a common product with molecular mass of 64,780
      Da which is consistent with dealkylation of the phosphonyl moieties. Furthermore,
      in the case of 1,2-dimethylpropyl methylphosphono-HuAChE, the change in the
      molecular mass and the kinetics of non-reactivability appear to occur in parallel
      indicating that dealkylation is indeed the predominant molecular transformation
      leading to 'aging' of phosphonyl-AChE adducts.

PMID- 9175883
TI  - Function of the repeated sequence in the 3' flanking region of the Escherichia
      coli rnpB gene on transcription termination and RNA processing.
AB  - The 3' flanking region of the Escherichia coli rnpB gene-encoding M1 RNA, the RNA
      component of RNase P, contains a 113 bp repeated sequence. This sequence,
      successively reiterating 3.5 times, includes the region for intrinsic
      termination. In vivo termination of transcription occurs mostly at the first
      terminator (T1). Analysis of deletions at the 3' flanking region revealed that
      the second terminator (T2) and third (T3) are functional in vivo and that the
      sequences preceding the region coding for an RNA-terminator hairpin and U-rich 3'
      tail are essential for efficient termination. Transcripts terminating at T2 and
      T3 were also processed at the 3' end in a manner similar to those terminating at
      T1.

PMID- 9175884
TI  - Expression of a highly basic peroxidase gene in NaCl-adapted tomato cell
      suspensions.
AB  - A tomato peroxidase gene, TPX2, that is only weakly expressed in the roots of
      young tomato seedlings is highly expressed in tomato suspension cells adapted to
      high external NaCl concentration. The protein encoded by this gene, with an
      isolectric point value of approximately 9.6, is found in the culture medium of
      the growing cells. Our data suggest that the expression of TPX2 in the salt
      adapted cells is not the result of the elicitation imposed by the in vitro
      culture or the presence of high NaCl concentration in the medium.

PMID- 9175885
TI  - The G protein alpha subunit (GP alpha1) is associated with the ER and the plasma
      membrane in meristematic cells of Arabidopsis and cauliflower.
AB  - Towards the elucidation of the cellular function(s) of GP alpha1, we have
      characterized its subcellular localization using immunofluorescence and cell
      fractionation. GP alpha1 is not present in nuclei or chloroplasts. It is a
      membrane-bound protein, and analysis of isolated endoplasmic and plasma membranes
      indicates a good correlation between GP alpha1 in both the plasma membrane and
      the ER compartment. Interestingly, these results may suggest more different
      functions for GP alpha1: it might be involved in transmission of extracellular
      signals across the plasma membrane and in the cytoplasm, and/or it may also be
      involved in regulating some aspects of the ER functions or membrane trafficking
      between both membranes.

PMID- 9175886
TI  - Motor cortex involvement during choice reaction time: a transcranial magnetic
      stimulation study in man.
AB  - It has been shown that transcranial magnetic stimulation can delay simple
      reaction time; this happens when the stimulation is delivered during the reaction
      time and over the cortical area which commands the prime mover of the required
      response. Although it is agreed that magnetic stimulation could be a useful tool
      for studying information processing in man, we argue that, because of the use of
      simple reaction time, the results reported so far are difficult to interpret
      within this theoretical framework. In the present paper, three experiments are
      reported. Six subjects participated in experiment 1 in which magnetic stimulation
      was delivered, at different times, during choice reaction time. The effects of
      the magnetic stimulation of the cortical area involved in the response (induced
      current passing forward over the motor representation of the responding hand),
      were compared to the effects of an electrical stimulation of the median nerve (H
      reflex). In a first control experiment (experiment 2a; 5 subjects), the coil was
      placed over the ipsilateral motor cortex (induced current passing backward over
      the motor representation of the non-responding hand) thus minimizing the
      probability to excite the same neural nets as in the first experiment. In a
      second control experiment (experiment 2b; 4 subjects), the coil was placed a few
      centimeters away from the subject's scalp thus ensuring no stimulation of any
      neural nets. The results show that: (1) the noise and the smarting of the skin
      associated with the coil discharge produce an intersensory facilitation thereby
      shortening reaction time (experiment 2a), (2) actually, the noise produced by the
      stimulation is sufficient to produce such a facilitatory effect (experiment 2b),
      (3) a stimulation over the area at the origin of the motor command causes a
      reaction time delay which counteracts this intersensory facilitation effect
      (experiment 1), (4) in this latter case, the closer the stimulation to the actual
      overt response, the longer the delay and (5) there is no trace of correlation
      between the amplitude of the motor evoked potential and the reaction time change.

PMID- 9175887
TI  - Human choroid plexus is an uniquely involved area of the brain in amyloidosis: a
      histochemical, immunohistochemical and ultrastructural study.
AB  - To better understand the characteristics of amyloid deposition in the choroid
      plexus, we examined autopsied brain by routine histology, immunohistochemistry,
      and electron microscopy in three group of patients: primary systemic amyloidosis
      (n = 7), cerebral amyloid angiopathy (CAA, n = 6), and controls (n = 3). Three of
      the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid
      deposits of the choroid plexus were seen in six of the seven cases of systemic
      light chain amyloidosis. Immunohistochemistry revealed that the deposited
      amyloids had reactivity for immunoglobulin light chain and amyloid P component.
      Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and
      major histocompatibility complex class II antigens were observed around the
      massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils
      along the epithelial basement membrane as well as in the vascular walls was
      ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits
      were consistently present in meningeal blood vessels and were often found in
      senile plaques of the cerebral parenchyma; congophilic amyloid deposits were
      absent in the choroid plexus. Choroid plexus epithelial cells exhibited
      immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C
      terminal-specific antibodies; in particular, consistent staining was obtained for
      the latter antibody. Immunoreactivity for amyloid beta protein (A beta) with
      monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial
      cells. These findings suggest that amyloid deposition of the choroid plexus
      depends on the major component protein in amyloidosis, and that the choroid
      plexus may produce APP and A beta protein although A beta amyloidosis is not
      evident in the choroid plexus.

PMID- 9175888
TI  - Anti-epileptogenic and anticonvulsant activity of L-2-amino-4-phosphonobutyrate,
      a presynaptic glutamate receptor agonist.
AB  - The protective effect of amygdaloid (focally administered) doses of the
      presynaptic metabotropic glutamate receptor agonist, L-2-amino-4
      phosphonobutyrate (L-AP4) was tested on the development of electrical kindling
      and in fully kindled animals. L-AP4 inhibited epileptogenesis at 10 nmol in 0.5
      microl buffer, by preventing the increase in both seizure score and
      afterdischarge duration. The effects were reversible after withdrawal of the
      drug, with all treated animals subsequently progressing to the fully kindled
      state at the same rate as control animals. The same concentration of the drug was
      also effective when injected into fully kindled animals. It significantly
      decreased the mean seizure score by 88% (P < 0.005) and increased the mean
      generalized seizure threshold (GST) by 85% (P < 0.005). The increase in GST was
      accompanied by a significant delay before the onset of generalized seizure and by
      a 37% reduction in generalized seizure duration. MPPG ((RS)-alpha-methyl-4
      phosphonophenyl glycine) a selective antagonist of L-AP4 at glutamate pre
      synaptic receptors inhibited the depressant effect of L-AP4 in a dose-dependent
      manner. MPPG (10 nmol) inhibited the antiseizure activity of L-AP4, whilst MPPG
      (40 nmol) reduced both the anti-epileptogenic and antiseizure activities of L
      AP4. MPPG (40 nmol) by itself had no effect on generalized seizure activity, and
      it had no detectable influence on the normal rate of kindled epileptogenesis.
      During in vitro studies using a microsuperfusion method, L-AP4 inhibited
      depolarization-induced release of [3H]D-aspartate from rat cortical synaptosomes
      (IC50 125.1 microM) and decreased the depolarization-evoked uptake of 45Ca2+ in a
      dose-dependent manner. Both actions of L-AP4 were reduced by the selective
      antagonist MPPG. When applied alone MPPG (200 microM) had no detectable action on
      veratridine-evoked 45Ca2+ uptake by the synaptosomes. These results suggest the
      mechanisms by which presynaptically active glutamate receptor agonists block the
      development of the chronically epileptic state induced by electrical kindling,
      and indicate that their anticonvulsive activity is due to inhibition of
      presynaptic glutamate and/or aspartate release following blockade of presynaptic
      Ca2+ entry.

PMID- 9175889
TI  - GABAergic control of Arg-vasopressin release from suprachiasmatic nucleus slice
      culture.
AB  - gamma-Aminobutyric acid (GABA) is contained in many neurons in the
      suprachiasmatic nucleus (SCN), and is considered to be a circadian entraining
      factor. Arg-vasopressin (AVP)-containing neurons represent one of the output
      paths from the SCN to other brain areas. We examined the effects of GABA,
      muscimol (GABA-A agonist), bicuculline (GABA-A antagonist), baclofen (GABA-B
      agonist) and phaclofen (GABA-B antagonist) on AVP release using SCN slice
      preparations in culture. SCN slices were prepared from coronally sliced brain
      tissue and cultured in organic tissue culture dishes with DMEM/N2 medium in a CO2
      (5%) incubator. The culture medium was changed at 3-h intervals until 9 h after 3
      h application of each drug. Concentrations of AVP in 1 ml aspirates of the medium
      were analyzed by EIA. Muscimol (1, 10 microM) increased and bicuculline (1, 10,
      100 microM) decreased the AVP release 3-6 h after application. However, baclofen
      and phaclofen had no apparent effects on AVP release. Riluzole (0.1 mM) and
      nipecotic acid (1 mM), GABA uptake inhibitors, increased AVP release 3-6 h after
      application. These results indicate that GABA promotes AVP release mediated by
      GABA-A receptors in the SCN.

PMID- 9175890
TI  - Effect of proximal axotomy on GAP-43 expression in cortical neurons in the mouse.
AB  - As an approach to understanding why central neurons fail to regenerate, we have
      studied the response to proximal axotomy of transcallosal neurons of the cerebral
      cortex of the mouse. Anatomical studies have indicated only very slight
      regenerative responses by this population of cortical neurons. To further examine
      the regenerative response of these cells, we have looked by in situ hybridization
      at the expression of GAP-43 mRNA following axotomy caused by a stab wound
      delivered within about 200 microm to 1.25 mm of the cell body. Axotomized
      transcallosal neurons were compared with near-by unaxotomized transcallosal
      neurons, as well as with distant unaxotomized cortical neurons in the
      contralateral hemisphere. All three populations of neurons had been pre-labeled
      with Fluoro-Gold to allow identification. No up-regulation of GAP-43 mRNA above
      background levels was detected for axotomized cortical neurons at 1, 3 or 7 days
      after injury. In contrast, increases in mean silver grain density of up to 8-fold
      were measured in axotomized spinal cord motor neurons used as positive controls.
      Thus, as a population, the transcallosal cortical pyramidal neurons did not show
      a significant regenerative response, as monitored by GAP-43 upregulation, even
      with very close axotomy. These results identify this population of neurons as
      among the least regenerative studied, and suggest that, on a molecular level,
      inherent neuronal properties play a role in the limited regenerative response to
      brain injury.

PMID- 9175892
TI  - 5-HT7 receptors mediate serotonergic effects on light-sensitive suprachiasmatic
      nucleus neurons.
AB  - Serotonin (5-HT) has been shown to phase shift circadian rhythms in mammals and
      to affect responses of the circadian system to light, but it is not clear which
      receptors are involved in these actions. We found that drugs which act as 5-HT1A
      receptor agonists suppressed photic responses of hamster SCN cells, but these
      drugs also exhibit high affinity for the recently cloned 5-HT7 receptor. We
      therefore studied the effects of 5-HT agonists and antagonists with differential
      affinities for 5-HT7 and 5-HT1A receptors on responses of hamster SCN cells to
      retinal illumination. We confirmed that the 5-HT receptor agonists 5-HT, 8-OH
      DPAT and 5-CT, dose-dependently reduced photic activation of SCN cells. These
      effects could be blocked by co-application of antagonists with high affinities
      for 5-HT7 receptors: ritanserin or clozapine. The 5-HT1A/B/D antagonist,
      cyanopindolol, which is inactive at 5-HT7 receptors, did not antagonize the
      actions of 8-OH-DPAT. Selective 5-HT1A antagonists, WAY100635 and p-MPPI, had
      weak or no antagonist effects on the responses to 8-OH-DPAT in the SCN, but they
      effectively antagonized the actions of 8-OH-DPAT in the hippocampus. In the
      cerebellar cortex where few 5-HT7 receptors are present, ritanserin failed to
      antagonize the effects of 8-OH-DPAT. Our results indicate that the 5-HT7 receptor
      subtype plays a major role in mediating the effects of 5-HT on photic responses
      of SCN cells in the hamster.

PMID- 9175891
TI  - Opioids suppress spontaneous and NMDA-induced inhibitory postsynaptic currents in
      the dorsal raphe nucleus of the rat in vitro.
AB  - Recently, local injection of morphine in the dorsal raphe nucleus (DRN) has been
      shown to increase serotonin release in the forebrain of unanesthetized rats. This
      study investigated the site of action of opioids in rat brain slices containing
      the DRN. Postsynaptic currents (PSCs), measured intracellularly under voltage
      clamp, were induced in serotonergic neurons with bath and microiontophoretic
      applications of NMDA to activate local neurons. Met-enkephalin (ENK) suppressed
      spontaneous and NMDA-induced GABAergic inhibitory PSCs. This effect, which was
      mimicked by the mu agonist DAMGO but not the kappa-agonist U50488 or the delta
      agonist DPDPE, was reversed by the mu antagonist CTOP. ENK also suppressed
      spontaneous and NMDA-induced glutamatergic excitatory PSCs. By searching with
      focal microiontophoretic NMDA applications, GABAergic and glutamatergic cells
      projecting on serotonergic neurons were found in the DRN and the adjacent
      periaqueductal gray. Consistent with the reduction in PSCs, ENK
      inhibited/hyperpolarized the great majority (81%) of non-serotonergic neurons
      recorded extra- and intracellularly in the DRN; the ENK effect reversed polarity
      at -99 +/- 9 mV, close to the potassium reversal potential. In contrast, ENK
      inhibited/hyperpolarized only 28% of serotonergic neurons; in the affected cells,
      the ENK effect, blocked by CTOP, had its reversal potential shifted with change
      of extracellular potassium in agreement with the value predicted by the Nernst
      equation for a potassium conductance; serotonin occluded the ENK inhibition.
      Taken together, these results indicate that opioids inhibit both local GABAergic
      and glutamatergic cells projecting onto DRN serotonergic neurons.

PMID- 9175893
TI  - Study of the origins of melanin-concentrating hormone and neuropeptide EI
      immunoreactive projections to the periaqueductal gray matter.
AB  - Previous studies have described the distribution of melanin-concentrating hormone
      (MCH) and neuropeptide EI (NEI) in the rat central nervous system (CNS), and
      revealed this peptidergic system to be primarily localized in neurons within the
      lateral hypothalamic area (LHA) and zona incerta (ZI). Moreover, an extensive MCH
      and NEI-immunoreactive (ir) fiber distribution has been described throughout the
      CNS, including a dense innervation within the periaqueductal gray matter (PAG).
      MCH and NEI have become important markers for the LHA, which harbors a variety of
      neuronal types as well as the medial forebrain bundle, a complex system of fibers
      which extends rostrocaudally throughout this area. In the present study, the
      projection patterns of MCH- and NEI-ir fibers within the PAG were characterized
      using a diamino benzidine immunoperoxidase procedure to localize each of these
      peptides in normal rat brain sections. MCH- and NEI-ir fibers were seen coursing
      through all of its subdivisions the entire length of the PAG, with a more
      condensed number of fibers in the periaqueductal medial zone. The primary
      origin(s) of these PAG afferents were determined in combined retrograde tracing
      immunofluorescent studies in which true blue (TB) was injected into various
      subdivisions of the PAG. TB-filled MCH-ir neurons were identified mainly in the
      rostral portion of the medial ZI (ZIm) and in the tuberal LHA (LHAt). Studies
      confirming this MCH-ir projection in which anterograde tracer (Phaseolus vulgaris
      leucoagglutinin) was injected into various regions in and around the LHA and ZI
      revealed a distinction in the PAG projections arising from these nuclei. ZIm
      injections resulted in labeled fibers mainly within the rostral dorsomedial and
      dorsolateral regions of the PAG, whereas injections in the LHAt revealed an
      innervation at intermediate and caudal levels in the ventrolateral region. Since
      the MCH and NEI fiber distribution patterns in the PAG are identical, this would
      suggest that these peptides are colocalized within the hypothalamus. Sequential
      immunofluorescent staining for MCH and NEI on tissue from rats who had received
      TB injections into the PAG confirmed this, and revealed that approximately 15% of
      all tracer-filled neurons in the LHA and ZI were both MCH- and NEI-ir. In fact,
      the vast majority of MCH-ir neurons within these regions also colocalize with
      NEI. Therefore, the MCH/NEI projection patterns within the PAG arise from two
      major sources: the ZIm which supplies afferents via a medial pathway that enters
      the PAG dorsally at rostral levels, and a pathway originating in the LHA that
      enters the PAG ventrally at more caudal levels. The ZIm and LHA are believed to
      be the primary, if not the only, sources of MCH and NEI projections to the PAG.

PMID- 9175894
TI  - Regulation of cyclic GMP levels in the rat frontal cortex in vivo: effects of
      exogenous carbon monoxide and phosphodiesterase inhibition.
AB  - A microdialysis method combined with a sensitive radioimmunoassay was used to
      monitor cGMP release in the frontal cortex of the anesthetized rats in vivo. We
      assessed the relative contribution of endogenous nitric oxide (NO), and effects
      of exogenous carbon monoxide (CO) and phosphodiesterase activity, as possible
      regulators of cortical CGMP levels. Perfusion with CO-saturated aCSF
      (approximately 1 mM CO) failed to significantly stimulate cortical cGMP levels.
      For comparison, cerebellar cGMP levels increased by 2-fold during CO stimulation,
      followed by a prolonged response that was fully reversible with the NO synthase
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). Cortical perfusion with
      zinc protopophyrin-IX (100 microM), a widely used inhibitor of the CO-generating
      enzyme heme oxygenase, suppressed cGMP levels by 50%, a response that
      spontaneously recovered in spite of the continuous presence of the
      metalloporphyrin. Perfusion with isobutylmethyl xanthine IBMX (1 mM) resulted in
      5-fold increase in cortical cGMP levels, as compared to basal levels without
      IBMX. In the presence of IBMX, L-NAME suppressed basal cortical cGMP levels by
      70% indicating that NO synthase activity generates the bulk of cGMP in this brain
      region, as previously shown for basal cGMP production in the hippocampus and the
      cerebellum. These data also emphasize a crucial role for phosphodiesterase
      activity in the maintenance of cGMP levels in vivo in the frontal cortex. The
      relatively weak responses to exogenous CO lend little support for a role of this
      gas in regulating basal cortical cGMP levels in vivo.

PMID- 9175895
TI  - Sources of subcortical projections to the superior colliculus in the ferret.
AB  - We have identified brainstem and other subcortical afferents to the superior
      colliculus (SC) in the ferret, by examining the pattern of retrograde labelling
      that resulted from unilateral injections of red and green fluorescent latex
      microspheres or of wheat germ agglutinin conjugated to horseradish peroxidase
      into different regions of this midbrain nucleus. Labelled neurons were found in
      many structures, including somatosensory, visual and auditory nuclei. These
      subcortical inputs are almost all bilateral, although most are primarily
      ipsilateral. Despite some differences in organization, the subcortical
      projections to the ferret SC broadly resemble those described in other species.
      Following injections of red and green microspheres in either the rostral and
      caudal or the medial and lateral regions of the SC, double-labelled cells usually
      accounted for less than 10% of the total number of retrogradely labelled cells,
      indicating that most of the subcortical neurons project to discrete regions of
      the SC. Many of these afferents show some topographic organization, which is much
      more evident along the rostrocaudal axis of the SC than in the medial-lateral
      dimension. The intercollicular projection is restricted mainly to the rostral SC
      and demonstrates a point-to-point organization. Most of the subcortical
      structures caudal to the central region of the SC were labelled mainly by the
      tracers injected in caudal SC, while those rostral to this region, including the
      zona incerta and the pretectal nuclei, were labelled largely by injections in
      rostral SC. These findings suggest that projections originating from nuclei
      posterior to the central region of the SC terminate principally in caudal SC
      whereas afferents from structures anterior to the central region project largely
      to rostral SC.

PMID- 9175896
TI  - Decrease in parietal cerebral hemoglobin oxygenation during performance of a
      verbal fluency task in patients with Alzheimer's disease monitored by means of
      near-infrared spectroscopy (NIRS)--correlation with simultaneous rCBF-PET
      measurements.
AB  - We used near-infrared spectroscopy (NIRS) to study non-invasively changes in
      cerebral hemoglobin oxygenation in the frontal and parietal cortex during
      performance of a verbal fluency task in patients with Alzheimer's disease (AD).
      Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases
      in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/-
      S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left
      superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed
      significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (
      4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29
      and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the
      left superior partietal cortex and on the left prefrontal cortex simultaneous
      increases in [HbO2] as well as [HbT] in both cortical regions in the healthy
      elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of
      the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2]
      and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and
      [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements
      showed a significant correlation both when calculated in a 'banana' shaped volume
      approximated by using cortical thresholds as well as when calculated in a
      semisphere volume of brain tissue beneath the optodes placed on the head surface
      (patients with AD, n = 10). The correlation was dependent on the assumed
      penetration depth of the near-infrared light and was best for all three NIRS
      variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of
      0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of
      regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during
      activation of brain function, probably mainly in degenerating brain areas, such
      as the parietal cortex.

PMID- 9175897
TI  - Glutamate and potassium stimulation of hippocampal slices metabolizing glucose or
      glucose and pyruvate.
AB  - Using 2-deoxyglucose phosphorylation as an index of glucose use and
      concentrations of selected intermediates to monitor metabolic pathways, responses
      of rat hippocampal slices to glutamate and K+ stimulation were examined. With
      glutamate, the glucose phosphorylation rate (GPR) increased, and the slices
      accumulated glutamate at a constant rate, for 10 min. The uptake rate at each
      glutamate level was matched, approximately, by the increase in GPR at that level,
      with 4 or 5 glutamate molecules accumulated for every glucose molecule
      phosphorylated. Phosphocreatine and ATP levels fell abruptly, and lactate rose,
      probably reflecting neuronal activity, found by others to be very brief in the
      presence of glutamate. K+ stimulation produced responses of phosphocreatine, ATP
      and lactate levels and of GPR similar to those due to glutamate. There were also
      prolonged changes in the levels of other metabolites: with both stimulants
      glucose 6-phosphate fell, and malate rose. The changes in malate may be the
      result of the participation of mitochondrial malate dehydrogenase in both citrate
      cycle and malate shuttle. Citrate and alpha-ketoglutarate rose only with K+. When
      pyruvate was added to the medium, resting GPR was reduced, but for both
      stimulants the relative increases in GPR with stimulation were the same as
      without pyruvate. The changes in metabolic intermediates in response to K+ were
      like those with glucose alone. But with glutamate, the rise in lactate was
      greatly diminished, and malate fell instead of rising. Glutamate interference
      with the transfer of both 3-carbon as well as 4- and 5-carbon intermediates from
      glia to neurons may explain these results. If so, this interference is greater
      with pyruvate supplementation than with glucose alone.

PMID- 9175898
TI  - Alteration of local cerebral glucose utilization following intravenous
      administration of heroin in Fischer 344 rats.
AB  - The 2-deoxyglucose method was used to study the effects of acute administration
      of small intravenous doses of heroin on rates of glucose utilization in rat brain
      to identify small brain regions that may be involved in the acute behavioral
      effects of heroin. In contrast to previous studies which have used relatively
      large doses, the doses of heroin used in this study have been shown to be self
      administered [Martin, T.J., Dworkin, S.I. and Smith, J.E., Alkylation of mu
      opioid receptors by beta-funaltrexamine in vivo: comparison of the effects on in
      situ binding and heroin self-administration in rats., J. Pharmacol. Exp. Ther.,
      272 (1995) 1135-1140.]. Administration of 18 microg/kg of heroin resulted in
      higher rates of glucose utilization in the medial olfactory tubercle, anterior
      nucleus accumbens and dorsolateral caudate while having no other effects on
      limbic structures compared to saline-treated animals. Conversely, the rate of
      glucose utilization was lower than control in the habenula, dorsal raphe, and
      central gray following adminstration of 18 microg/kg of heroin. Administration of
      two higher doses (60 and 100 microg/kg) resulted in lower rates of glucose
      utilization in the thalamus, habenula, inferior colliculus, dorsal raphe and
      central gray compared to saline. The higher rates of glucose utilization in the
      limbic areas were specific for the lowest dose of heroin, whereas the effect of
      lowering the rate of glucose utilization compared to control in the thalamus and
      inferior colliculus were an increasing function of dose. In the habenula and
      dorsal raphe, however, the dose-effect function was inverted. These data indicate
      that the alterations of glucose utilization in rat brain by heroin are site
      specific and the systems involved as well as the nature of the alteration differs
      for individual doses of heroin.

PMID- 9175899
TI  - Dopamine-immunoreactivity in the rat mesencephalic trigeminal nucleus: an
      ultrastructural analysis.
AB  - The ultrastructure and distribution of dopaminergic boutons within the rat
      mesencephalic trigeminal (Me5) nucleus was examined with the use of
      electronmicroscopic immunocytochemistry. A total of 5102 boutons, comprising
      axosomatic and axodendritic synaptic terminals as well as non-synaptic boutons
      (or varicosities), located in the ventrocaudal portion of Me5 was analysed.
      Approximately 20% of these boutons were dopamine-immunoreactive. Morphological
      analysis showed that the dopaminergic synaptic terminals, axodendritic as well as
      axosomatic, were exclusively of the S- and G-bouton type; they contained,
      respectively, small spherical vesicles or small pleomorphic vesicles in
      combination with large granular dense-cored vesicles. All dopaminergic
      varicosities in the Me5 were of the G-bouton type. Quantitative analysis revealed
      that most of the dopaminergic synaptic terminals in the Me5 nucleus contacted
      dendrites, while only a minority (12%) contacted Me5 somata. This dopaminergic
      somatic input comprised about half (52%) of the total axosomatic input on Me5
      neurons. The present results and previous findings with respect to the prominent
      serotonergic component of the axosomatic input to Me5 neurons indicate that
      dopamine and serotonin account for most of the axosomatic input in the
      ventrocaudal part of the Me5 nucleus. In fact, the present results seem to
      support previous observations regarding the existence of a population of afferent
      neurons in which dopamine and serotonin are colocalized.

PMID- 9175900
TI  - The locus coeruleus of the Japanese monkey (Macaca fuscata) does not express mu
      opioid receptor-like immunoreactivity.
AB  - It is well known that locus coeruleus (LC) of the rat shows intense mu-opioid
      receptor-like immunoreactivity (MOR-LI). In the course of our study on the
      distribution of MOR-LI in the brain of the Japanese monkey (Macaca fuscata),
      however, no MOR-LI was found in the LC although the distribution pattern of MOR
      LI in other regions of the lower brainstem of the monkey was essentially the same
      as that observed in the rat. It was also found that immunoreactivity for Met
      enkephalin, the most potent endogenous ligand for MOR, was intense in the rat LC,
      but very weak, if any, in the monkey LC. MOR may not be expressed in the monkey
      LC.

PMID- 9175901
TI  - Suppression of neuropathic pain by a naturally-derived peptide with NMDA
      antagonist activity.
AB  - Chronic pain may result from hyperexcitability following activation of spinal
      NMDA receptors. A naturally-derived mammalian peptide, histogranin, may possess
      NMDA antagonist activity. This study explored the possibility that stable analog
      [Ser1]Histogranin (SHG) could reduce chronic pain. Neuropathic pain was induced
      using the chronic constriction injury model (CCI). Intrathecal injection of SHG
      markedly attenuated the hyperalgesia and allodynia resulting from CCI, nearly
      normalizing responses. These results suggest that the natural peptide histogranin
      may be a novel adjunct in neuropathic pain management.

PMID- 9175902
TI  - Melatonin administration protects CA1 hippocampal neurons after transient
      forebrain ischemia in rats.
AB  - Melatonin administered at the beginning of cerebral reperfusion protected CA1
      neurons against 10, 20 and 30 min of transient forebrain ischemia.
      Intraperitoneal injections of saline or melatonin (10 mg/kg) were given after 0,
      2 and 6 h, or 1, 2 and 6 h of cerebral reperfusion, or 30 min prior to ischemia.
      One week later, quantitative histological analysis demonstrated that CA1 neuronal
      density was significantly increased in the melatonin groups that were treated at
      0, 2, 6 h compared to the saline-treated controls. Ischemic protection of CA1 was
      lost in the animals in which the melatonin treatment was delayed by 1 h, or given
      30 min prior to the ischemia.

PMID- 9175903
TI  - Evidence that hypothalamic neuropeptide Y gene expression and NPY levels in the
      paraventricular nucleus increase before the onset of hyperphagia in experimental
      diabetes.
AB  - Neuropeptide Y (NPY) is the most potent endogenous orexigenic signal. Several
      lines of evidence indicate that the site of NPY action in transducing feeding
      signal may reside in the paraventricular nucleus (PVN) and neighboring sites in
      the hypothalamus. To test the hypothesis that an increase in NPY activity in the
      ARC-PVN pathway precedes the onset of diabetic hyperphagia, we evaluated NPY
      levels in seven hypothalamic nuclei and NPY gene expression in the hypothalamus
      at 48, 72 or 96 h after streptozotocin (STZ) treatment in rat. In STZ-treated
      diabetic rats, NPY gene expression in the hypothalamus and NPY levels only in the
      PVN significantly elevated at 48 h, while hyperphagia occurred sometimes after 48
      h post-injection. These results show that augmentation in NPY neuronal activity
      in the ARC-PVN axis precedes the onset of increased food intake produced by STZ
      induced insulinopenia. These findings affirm the hypothesis that increased NPY
      neurosecretion in the PVN may underlie the diabetes-induced hyperphagia.

PMID- 9175904
TI  - Effect of dibutyryl cyclic AMP on axoplasmic transport in the hippocampus.
AB  - The effect of dibutyryl cyclic AMP (dbcAMP) on axoplasmic transport of cultured
      hippocampal neuron cells from postnatal 1-day mice was analyzed with a computer
      assisted video-enhanced differential interference contrast microscope system.
      Dibutyryl cyclic AMP increased the axoplasmic transport in both anterograde and
      retrograde directions. The number of particles flowing in the neurites was
      increased by 0.5 mM dbcAMP. The peak reached about 160% of the initial value. The
      instantaneous velocity of axoplasmic transport was also increased by 0.5 mM
      dbcAMP. The average velocity of anterograde and retrograde direction changed
      respectively from 1.95 +/- 1.01 microm/s (n = 55) to 2.66 +/- 1.26 microm/s (n =
      58) and from 1.94 +/- 0.85 (n = 57) to 2.39 +/- 0.93 (n = 57). Rates were 136.1
      and 123.1%, respectively. Previously, we have found that acetylcholine suppressed
      and adrenaline increased the axoplasmic transport in superior cervical ganglion
      cells. These effects are related to the amount of endogeneous cAMP. The results
      of the present report suggest that endogeneous cAMP is also related to
      hippocampal axoplasmic transport.

PMID- 9175905
TI  - Phospholipid breakdown and choline release under hypoxic conditions: inhibition
      by bilobalide, a constituent of Ginkgo biloba.
AB  - A marked increase of choline release from rat hippocampal slices was observed
      when the slices were superfused with oxygen-free buffer, indicating hypoxia
      induced hydrolysis of choline-containing phospholipids. This increase of choline
      release was suppressed by bilobalide, an ingredient of Ginkgo biloba, but not by
      a mixture of ginkgolides. The EC50 value for bilobalide was 0.38 microM. In ex
      vivo experiments, bilobalide also inhibited hypoxia-induced choline release when
      given p.o. in doses of 2-20 mg/kg 1 h prior to slice preparation. The half
      maximum effect was observed with 6 mg/kg bilobalide. A similar effect was noted
      after p.o. administration of 200 mg/kg EGb 761, a ginkgo extract containing
      approximately 3% of bilobalide. We conclude that ginkgo extracts can suppress
      hypoxia-induced membrane breakdown in the brain, and that bilobalide is the
      active constituent for this effect.

PMID- 9175906
TI  - Single restraint stress sensitizes acute chewing movements induced by
      haloperidol, but not if the 5-HT1A agonist 8-OH-DPAT is given prior to stress.
AB  - The objective of this study was two-fold: (i) to analyze behavioral sensitization
      to haloperidol 2 weeks after single restraint stress, and (ii) to establish the
      effects of 8-OH-DPAT treatment prior to stress on sensitized behavioral
      responses. Overall behavior was analyzed and not only catalepsy, but also
      sedation (immobility), grooming, exploration and vacuous chewing movements were
      evaluated. Results indicated that single restraint stress induced a long-lasting
      sensitization of acute vacuous chewing movements induced by haloperidol (0.25,
      0.5 mg/kg i.p.). Interestingly, this behavioral sensitization was prevented by 8
      OH-DPAT (0.35 mg/kg s.c.) prior to stress. Finally, haloperidol-induced sedation
      was not disrupted by either restraint stress or 8-OH-DPAT treatment.

PMID- 9175907
TI  - Expression of CD28, CTLA4, CD80, and CD86 molecules in patients with autoimmune
      rheumatic diseases: implications for immunotherapy.

PMID- 9175909
TI  - Signaling events in T lymphocytes leading to cellular activation or programmed
      cell death.

PMID- 9175908
TI  - Analysis of CD80 and CD86 expression on peripheral blood B lymphocytes reveals
      increased expression of CD86 in lupus patients.
AB  - We screened peripheral blood mononuclear cells from 13 SLE patients, all having
      quiescent disease at the time of analysis, 12 allergy patients, and 21 normal
      subjects for the expression of CD80 (B7-1) and CD86 (B7-2, B70) on small
      (resting) and large (activated) subsets of CD19+ B cells. The percentage of CD86+
      cells was significantly higher in all B cell subsets in the SLE patients compared
      to either normal controls or allergy patients. No differences in the mean
      percentage CD86+ stained B cells (CD19+) were found when comparing the allergy
      patients and the normal controls. The percentage of CD80+ cells in the large
      activated B cell (CD19+) subset of the SLE patient population was significantly
      higher than in the comparable subset from the normal controls and the allergy
      patients. Comparison of the small resting B cell subset did not reveal a
      significant difference in CD80 expression between the normal controls, the
      allergy patients, and the SLE patients. Our findings suggest that the B7 family
      of molecules, and CD86 in particular, may reflect immunologic dysregulation in
      patients with autoimmune disease and may reflect a state facilitating heightened
      B cell activity and hypergammaglobulinemia that occur in active SLE.

PMID- 9175911
TI  - Murine postthymectomy autoimmune oophoritis develops in association with a
      persistent neonatal-like Th2 response.
AB  - Autoimmune oophoritis develops in some patients despite evidence of impaired
      cellular immunity. Here, using the murine postthymectomy model of autoimmune
      oophoritis, we investigate the hypothesis that neonatal thymectomy induces
      autoimmune oophoritis by disrupting the normal postnatal balance of T helper cell
      regulation. Stimulated CD4+ splenic lymphocytes from adult mice sham-operated as
      neonates produced the expected T helper type 1 (Th1) predominant response
      normally seen in adult mice (low levels of interleukin-4 and high levels of
      interferon gamma). In contrast, cells from adult mice thymectomized as neonates
      produced an inappropriate neonatal-like Th2-predominant response (high levels of
      interleukin-4 and low levels of interferon-gamma). Manipulations that restored
      the postnatal shift to an adult Th1-dominant pattern ameliorated the autoimmune
      oophoritis. Thus, neonatal thymectomy abrogates the postnatal shift to a Th1
      dominant pattern, and the resulting persistent neonatal-like Th2-dominant
      response is tightly associated with the development of postthymectomy autoimmune
      oophoritis. These results (i) suggest that the postnatal shift to the normal
      adult Th1/Th2 balance is established by a thymus-dependent process and (ii) raise
      the possibility that specific genetic defects, as yet to be determined, might
      mimic the effect of neonatal thymectomy in this model, impair the development of
      normal Th1/Th2 balance, and be a cause autoimmunity. These results hold
      implications for the pathogenesis and possibly for the therapy of autoimmune
      polyglandular failure in humans.

PMID- 9175910
TI  - Expression of Fas ligand and its receptor in cutaneous lupus: implication in
      tissue injury.
AB  - Fas ligand (FasL) is a type II membrane protein which belongs to the tumor
      necrosis factor family. Ligation of its receptor (Fas/APO-1/CD95) by FasL induces
      apoptosis of Fas-expressing cells. However, the in vivo function of these
      molecules in cutaneous immunity is presently unknown. In the present study, we
      investigated the involvement of Fas and FasL in the pathogenesis of cutaneous
      lupus by immunohistochemical methods. In normal skin, expression of Fas was
      observed on keratinocytes in the basal to granular layers. Unexpectedly, FasL was
      constitutively expressed on histiocytes in the dermis. In specimens of cutaneous
      lupus, Fas was expressed on infiltrating lymphocytes, as well as on keratinocytes
      as observed in normal skin. FasL was expressed on a portion of infiltrating CD4+
      T cells and on histiocytes more frequently than those in normal skin. Double
      staining indicated that these FasL-expressing histiocytes were CD68 positive
      macrophages. Especially, FasL-expressing macrophages were distributed around
      appendages such as hair follicles. These results suggest the Fas/FasL interaction
      may be involved in the destruction of hair follicles which is a characteristic
      feature of cutaneous lupus.

PMID- 9175912
TI  - Gammalinolenic acid and dihomogammalinolenic acid suppress the CD3-mediated
      signal transduction pathway in human T cells.
AB  - Gammalinolenic acid (GLA; 18:3n6) and dihomogammalinolenic acid (DGLA; 20:3n6)
      suppress lymphocyte activation, and GLA administration reduces joint swelling and
      tenderness in rheumatoid arthritis patients with active synovitis. In an effort
      to dissect the mechanisms whereby GLA, DGLA, and other fatty acids influence
      lymphocyte function, we examined their effects on anti-CD3 monoclonal antibody
      (mAb)-mediated early signaling events in human T cells. Peripheral blood
      mononuclear cells from healthy individuals were incubated overnight at 37 degrees
      C with or without 10 microg/ml fatty acid and then loaded with the calcium
      binding fluorescent dye indo-1. Fatty acids did not affect the efficiency of indo
      1 loading, and they did not alter cell surface membrane expression of the CD3
      molecule. Anti-CD3 mAb (G19-4)-induced intracellular calcium [(Ca2+)i] changes
      were monitored by flow cytometry in negatively selected human T cells. The ratio
      of violet to blue fluorescence, which is proportional to (Ca2+)i, was measured
      over time. Cells enriched with GLA and DGLA but not cells enriched with
      eicosapentaenoic acid (20:5n3) displayed a significant reduction in anti-CD3 mAb
      induced early and late (Ca2+)i responses. T cells loaded with GLA, DGLA, or
      medium alone displayed similar increases in (Ca2+)i in response to the
      endoplasmic reticulum Ca2(+)-ATPase inhibitor thapsigargin. Anti-CD3 mAb-mediated
      inositol phosphate production was also diminished in GLA- and DGLA-treated cells.
      These experiments suggest that GLA and DGLA suppress T cell activation by
      interfering with early events in the signal transduction pathway.

PMID- 9175913
TI  - Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T
      lymphocytes to extracellular matrix proteins.
AB  - Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can
      activate neutrophils to adhere to endothelium, degranulate, and cause endothelial
      cell injury. These data have lead to the hypothesis that the T cell inflammatory
      response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to
      stimulation of neutrophils by ANCA. So far there is no evidence for a direct
      effect of ANCA on lymphocytes. The present study was designed to examine whether
      lymphocytes can be directly stimulated by ANCA to adhere to endothelial
      extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were
      tested for their ability to increase adhesion of human T lymphocytes to
      fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with
      human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent
      manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact
      ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG
      containing ANCA or control human IgG, respectively; P = 0.0045). The same
      induction of adhesion to fibronectin, laminin, and intact ECM was observed when
      the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG.
      Similarly, ANCA-enriched IgG produced in mice increased the adhesion of
      lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/-
      4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control
      mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can
      directly stimulate lymphocytes to adhere to endothelial ECM and to induce the
      vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA
      stimulate lymphocytes to adhere to ECM.

PMID- 9175914
TI  - Inhibition of the p50 (NKkappaB1) subunit of NF-kappaB by phosphorothioate
      modified antisense oligodeoxynucleotides reduces NF-kappaB expression and
      immunoglobulin synthesis in murine B cells.
AB  - NF-kappaB is a regulatory protein of immune response genes and a candidate for
      targeting in immunosuppressive therapy. NF-kappaB proteins are formed from
      components of which p50 (NFkappaB1) is a subunit. By targeting p50 gene
      expression with specific antisense 3' phosphorothioate-oligodeoxynucleotides (3'
      PS-ODNs), an effect upon NF-kappaB regulation and immunoglobulin synthesis in
      murine B cells was achieved. A 49% decrease in p50 protein was induced by
      treatment of WEHI 231 B cells with p50 antisense 3' PS-ODNs and not by control 3'
      PS-ODNs. p50 antisense specifically reduced the expression of NF-kappaB by 51%,
      but not the transcription factor, Oct-1. In the BXSB murine model of
      autoimmunity, p50 antisense inhibited NF-kappaB expression and total IgM and IgG
      synthesis, but, more importantly, dsDNA antibodies were reduced 90%. These
      results validate the use of p50 antisense to reduce NF-kappaB expression and, by
      downregulating the immune response, has application in the treatment of
      autoimmune disorders.

PMID- 9175915
TI  - Absence of the IL-7 receptor component CDw127 indicates that gamma(c) expression
      alone is insufficient for IL-7 to modulate human neutrophil responses.
AB  - It has been proposed that neutrophils are targets for interleukin-7 (IL-7)
      because this cytokine was found to increase the number of murine immature
      neutrophils in vivo. In addition, some nonhuman myeloid cell lines were shown to
      express the IL-7 receptor (IL-7R). Moreover, it was recently discovered that
      human neutrophils constitutively express the common gamma chain (gamma(c)), known
      to be a component of not only IL-7R, but also IL-2R, IL-4R, IL-9R, and IL-15R.
      Among these, we have recently observed that IL-4 and IL-15 are neutrophil
      agonists. All of the above observations prompted us to study IL-7-human
      neutrophil interactions. In this study, we investigated potential effects of IL-7
      on a range of neutrophil responses. Although we were able to confirm the presence
      of the gamma(c) component on human neutrophils, we report, for the first time,
      that these cells lack the CDw127 component of IL-7R. When studying potential
      modulatory effects of IL-7 on human neutrophils, we found that IL-7 does not
      induce respiratory burst, phagocytosis, or cytoskeletal functions and does not
      alter gene expression. Positive controls were included in each assay and the
      expected results were obtained. In addition, in contrast to IL-4 and IL-15, we
      found that neutrophil apoptosis is not modulated by IL-7, while granulocyte
      macrophage colony-stimulating factor, used here as control, strongly delayed this
      process as expected. We conclude that the sole expression of gamma(c) on human
      neutrophils is insufficient to modulate neutrophil responses with respect to the
      studied functions. Therefore, it cannot be proposed, based on studies performed
      with nonhuman cells or cell lines, that human neutrophils are targets for IL-7.

PMID- 9175916
TI  - Frequency of clonal dominance in the specific antibody response to DNP-HSA in CBA
      and C57BL mice reflects their susceptibility to age-associated development of
      monoclonal gammopathies.
AB  - The effects of age, genetic background, and neonatal thymectomy on the levels and
      the heterogeneity of the specific antibody response were investigated in an
      experimental mouse model. Both intact and neonatally thymectomized (NTx)
      C57BL/KaLwRij (C57BL) and CBA/BrARij (CBA) mice were immunized at the age of 3
      ("young") or 22 months ("old"). Highly sensitive antigen-specific immunoblotting
      techniques (ABL), in combination with agar-electrophoresis and isoelectric
      focusing (IEF), were used to investigate total specific antibody levels, the
      number of responding antigen-specific clonotypes, and the dominance of responding
      B cell clones in the antibody response against dinitrophenylated human serum
      albumin. After immunization, the specific antibody levels progressively increased
      in all experimental groups with the exception of old C57BL mice. All mice
      responded with a specific polyclonal heterogeneous response. In addition, some
      mice showed a clonal dominance of antibody-producing cells, as is reflected in
      the appearance of distinct homogeneous antibody components (H-Ab) in the sera.
      This clonal dominance was scarce in CBA mice but frequent in C57BL mice. Age at
      time of immunization and NTx had little if any additive effect on the incidence
      of H-Ab in either mouse strain. All dominant clones showed different
      electrophoretic mobility, indicating the proliferation of various clonotypes and
      not a strain-specific dominance of one clone. In old C57BL mice the specific
      antibody response was more restricted in heterogeneity, as is illustrated by more
      visible spectrotype bands in IEF and subsequent ABL. Hence, in old C57BL mice
      smaller amounts of specific antibodies were produced by fewer clones. Still, the
      incidence of H-Ab in this group was the same as that in the group of young C57BL
      mice. This indicates that at old age the responding B cell clones are more prone
      to becoming clonally dominant in C57BL mice. This tendency correlates with the
      high incidence of spontaneously developing monoclonal gammopathies in aging C57BL
      mice.

PMID- 9175917
TI  - Changes in intracellular cytokine levels in lymphocytes induced by measles virus.
AB  - We investigated the changes in intracellular cytokine levels in different
      lymphocyte populations induced by measles virus (MV). MV-infected and uninfected
      peripheral blood mononuclear cells were cultured with phorbol 2-myristate 13
      acetate plus ionomycin in the presence of monensin for 10 hr. Surface antigen and
      intracellular cytokines, interleukin (IL)-2, interferon (IFN)-gamma, and IL-4,
      were stained simultaneously and analyzed by flow cytometry. The percentage of
      cells that expressed IL-2 and IFN-gamma was significantly increased in MV
      infected CD3+, CD4+, and CD8+ lymphocytes and alphabeta T lymphocytes compared
      with that in uninfected lymphocytes. In gammadelta T lymphocytes, expression of
      IFN-gamma, not IL-2, was increased in MV-infected cells compared with that in
      uninfected cells. IL-2 was increased mainly in MV-infected CD4+ lymphocytes and
      alphabeta T lymphocytes, whereas IFN-gamma was increased mainly in MV-infected
      CD8+ lymphocytes and gammadelta T lymphocytes. Expression of IL-4 was unaffected
      by MV infection. These results demonstrate that MV enhances intracellular levels
      of type 1 cytokines during the acute phase of measles.

PMID- 9175918
TI  - In vivo but not in vitro stimulations rescue of the defective class switching to
      IgG or IgA in B-cells of immunodeficiency with hyper IgM.
AB  - In an X-linked immunodeficiency with hyper IgM (X-HIM), several mutations of
      genes coding for CD40 ligand are responsible for B-cell defects. However, it is
      controversial whether the defective class switching from IgM to IgG or IgA but
      not IgE is rescued by in vitro stimulations or not. In six X-HIM patients,
      signaling through CD40 induced IgE but not IgG or IgA secretion in vitro. When
      transferred into SCID mice, however, B-cells of X-HIM patients secreted as much
      IgG and IgA as those of healthy controls. Moreover, sIgG and sIgA expressions
      were also induced by the in vivo stimulation. These results support that B-cells
      of X-HIM patients are defective of in vitro class switching from IgM to IgG or
      IgA and show that the in vivo stimulations rescue the defective class switching
      and suggest that the class switching of IgE and that of IgG or IgA might be
      regulated quite differently.

PMID- 9175919
TI  - Neutrophil-mediated damage to vascular endothelium in the spontaneously
      hypertensive rat.
AB  - Lysis of aortic endothelial cells (EC) by neutrophils from spontaneously
      hypertensive rats (SHR) was investigated using a nonradioactive cytotoxicity
      assay. Interleukin-1-activated EC, but not unstimulated EC, were effective target
      cells for lysis by SHR neutrophils. Supernatants from activated neutrophil did
      not exert a cytotoxic effect on EC. Inhibitors of reactive oxygen species did not
      affect the cytotoxicity of neutrophils on EC. In contrast, inhibitors of serine
      protease and elastase markedly inhibited the cytotoxicity of neutrophils on EC.
      Antibodies against the endothelial cell surface ligands ICAM-1 (CD54) and E
      selectin (CD62E) inhibited the adhesion and cytotoxicity of activated neutrophils
      on EC. The cytotoxicity of neutrophils required direct cell-to-cell contact
      because separating them with a microporous membrane abrogated the neutrophil
      mediated cytotoxic activity. These results demonstrate that SHR neutrophils
      possess potent cytotoxicity against cytokine-activated EC. Neutrophil-mediated
      damage of EC could contribute to organ damage in hypertension under conditions of
      local or systemic activation of neutrophils.

PMID- 9175920
TI  - Experimental hepatitis in neonatally thymectomized mice: transfer of disease and
      the role of T cells.
AB  - Using neonatally A/J thymectomized mice, we have produced chronic hepatitis by
      administration of sublethal doses of Propionibacterium acnes and
      lipopolysaccharide (LPS). Our goal in this unique model was to evaluate the
      effector cell population required to generate chronic hepatitis by transferring
      spleen cells or splenic subpopulations derived from donor thymectomized mice with
      chronic hepatitis into congenic recipient nonimmunized thymectomized or sham
      thymectomized animals. Several key observations were made regarding the ability
      to induce and to transfer disease. First, an inflammatory liver injury in
      neonatally thymectomized (NTx) mice was readily generated using sublethal doses
      of P. acnes and LPS. Second, the lesions were persistent and associated with the
      production of autoantibodies to liver-specific lipoprotein and anti-nuclear
      antibodies. Third, these features were not found in comparably injected
      nonthymectomized control A/J mice. Fourth, the same liver injury was transferred
      to neonatally thymectomized but otherwise naive mice by the transfer of donor
      spleen cells from affected mice previously induced to develop experimental
      hepatitis. Fifth, the transfer of this liver injury could not be achieved using T
      cell-depleted spleen cells. Deletion of CD4+ T cells or CD8+ T cells by
      sensitized spleen cells resulted in suppression of the transferred liver injury.
      In contrast, transfer of nylon wool adherent splenic T cells induced severe
      hepatitis. These data suggest that the chronic liver injury induced in NTx mice
      by administration of P. acnes and LPS involves a breakdown in tolerance
      accompanied by the appearance of autoantibodies and that nylon wool adherent CD4+
      and CD8+ T cells play important roles in the modulation of liver injury.

PMID- 9175921
TI  - Screening of SLE sera using purified recombinant Sm-D1 protein from a baculovirus
      expression system.
AB  - The Sm-D1 polypeptide is a major target of autoantibodies diagnostic for systemic
      lupus erythematosus (SLE). The cDNA encoding the human antigen was expressed as a
      full-length, nonfusion protein using a eukaryotic baculovirus expression system.
      This recombinant version of Sm-D1 (rSm-D1) was purified to apparent homogeneity
      by a combination of differential extraction steps and FPLC chromatography. A
      direct antibody-binding ELISA was developed using the purified antigen. There was
      96% correlation between the rSm-D1 and bona fide Sm-D1 from either HeLa cells or
      rabbit thymus when tested against Sm-positive patient sera by ELISA. The
      baculovirus-expressed Sm-D1 is reactive not only with patient anti-Sm sera, but
      also with anti-Sm monoclonal antibodies. Our results suggest that this rSm-D1
      mimics the bona fide sources, providing a valuable addition to the roster of
      antigens available for SLE screening, epitope mapping and overall structure
      study.

PMID- 9175923
TI  - Eurosurveillance approaches its first birthday and Eurosurveillance Weekly is
      born.

PMID- 9175922
TI  - Re: IgA deficiency and common variable immunodeficiency.

PMID- 9175924
TI  - WHO Expert Committee on Biological Standardization. Highlights of the 46th
      meeting, October 1996.

PMID- 9175925
TI  - Do sex hormones modulate the synovial macrophages in rheumatoid arthritis?

PMID- 9175926
TI  - Unusual but memorable. Lead arthropathy.

PMID- 9175927
TI  - Rheumatoid factors: where are we now?

PMID- 9175928
TI  - Phenotypic modulation of chondrocytes as a potential therapeutic target in
      osteoarthritis: a hypothesis.

PMID- 9175929
TI  - Osteoarthrosis of the hip in women and its relation to physical load at work and
      in the home.
AB  - OBJECTIVES: The aim of this case referent study was to investigate the relation
      between physical workload and osteoarthrosis of the hip in women. METHODS: The
      study base comprised all women of ages 50-70 years, living in five counties and
      four towns in Sweden 1991-1994. Cases (n = 230), who had undergone total hip
      replacement for primary osteoarthrosis of the hip were identified by means of the
      Swedish National Register of Total Hip Replacements, and the referents (n = 273)
      were women without hip problems randomly selected from the study base. All women
      were interviewed about state of health, smoking habits, occupational history,
      work in the home, sports activities, etc. Each subject's history of occupational
      work and work in the home up to the age of 50 was divided into periods within
      each of which the work tasks were similar, and a questionnaire for each such
      period was filled in by the participants. On the basis of information given by
      the referents, the women were classified as having had low, medium, and high
      exposure to different factors. Relative risks (RRs) and 95% confidence intervals
      (CI) were calculated. RESULTS: Physically demanding tasks at work and in the home
      were associated with increased RRs of osteoarthrosis of the hip in those with
      high exposure compared with the low exposure group. A RR in the range of 2 or
      higher was found for those who frequently jumped or moved between different
      levels (RR = 2.1, CI 1.9, 4.2), who frequently climbed stairs (RR = 2.1, CI 1.2,
      3.6), and who had physically demanding tasks outside occupational life (RR = 2.3,
      CI 1.5, 3.6). The highest RR (RR = 4.3, CI 1.7, 11.0) was found for those exposed
      to high physical loads both at work and during sports activities. CONCLUSION:
      High physical loads at work and in the home up to the age of 50 seem to be risk
      factors for development of severe osteoarthrosis of the hip in women.

PMID- 9175930
TI  - Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and
      hyaluronan in arthritic and normal knees.
AB  - OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) and keratan
      sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee
      synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or
      rheumatoid arthritis (RA), to test whether these variables may be used as markers
      of the OA process. METHODS: OA was subdivided into large joint OA (LJOA), nodal
      generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition
      (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA
      knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS
      epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using
      monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of
      cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with
      1:9 dimethylmethylene blue. RESULTS: Increased SF 3-B-3 concentrations and 3-B
      3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3
      and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced
      in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with
      normal. GAG and HA concentrations were decreased in both OA and RA. No
      correlations with radiographic scores were observed, but SF 7-D-4 was lower in
      'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with
      bilateral samples there were strong correlations between right and left knees for
      all SF variables. CONCLUSIONS: Changed concentrations of SF CS and KS can be
      detected in OA with a profile that differs from that seen in RA. Clinical
      subgrouping and local joint inflammation may influence these measures, supporting
      different pathogenesis within OA subgroups and requirement for careful patient
      characterisation in SF studies.

PMID- 9175931
TI  - Prevalence of shoulder pain in the community: the influence of case definition.
AB  - OBJECTIVE: To compare estimates of the occurrence of shoulder pain according to
      (a) different approaches to defining 'shoulder' and (b) restricting the
      definition to only include those with associated disability. METHODS: A postal
      questionnaire survey was sent to a sample of 500 patients registered with a
      general practice in south Manchester. After additional mailings to non
      responders, 312 questionnaires were returned (66% adjusted response rate). Four
      definitions of shoulder pain were used to estimate the occurrence of symptoms
      derived from answers to the questionnaire. Two were based on questions asking
      directly about pain in the shoulder and the upper trunk and neck region
      respectively and two were based on markings on a pain drawing in the shoulder
      complex and the upper trunk respectively. To determine the occurrence of
      disabling shoulder pain responders were subsequently approached for interview. Of
      the responders, 232 (74%) were successfully interviewed. Those indicating that
      they were suffering from 'current' shoulder symptoms, pain on the day of
      interview, were asked to complete a short, 23 item, questionnaire enquiring about
      disability in daily living associated with such symptoms. RESULTS: In total 160
      (51%) people reported shoulder pain according to at least one definition. This
      one month period prevalence ranged from 31% to 48% across the four definitions
      with the lowest estimate being for the question asking directly about shoulder
      symptoms. In total 84 people (27% of all respondents) answered positively to all
      four definitions. Only seven people who answered positively when asked directly
      about shoulder pain did not indicate symptoms on the pain drawing in the shoulder
      complex. By contrast 65 (30%) of those answering negatively to the direct
      question about shoulder pain indicated symptoms on the pain drawing in the upper
      trunk region or answered positively to the direct question about pain in the
      upper trunk or neck region. However only 19 (9%) of those answering negatively to
      the direct question indicated symptoms in the shoulder complex on the pain
      drawing, compared with 38 (18%) indicating symptoms in the upper trunk region and
      59 (27%) symptoms in the upper trunk and neck region. Limiting the definition to
      only include current symptoms with some associated disability (at least one item
      on the disability questionnaire being answered positively) restricted the point
      prevalence to 20% (n = 46). CONCLUSIONS: Using a pain drawing based definition
      with case ascertainment restricted to an area in and around the shoulder complex
      is recommended for surveys assessing the occurrence of shoulder symptoms in the
      general population. To solve the problem of the poor specificity associated with
      symptom based definitions it is useful to incorporate an additional
      classification to restrict the definition to more disabling problems.

PMID- 9175932
TI  - Increase in age at onset of rheumatoid arthritis in Japan over a 30 year period.
AB  - OBJECTIVES: To determine changes in demographic variables and severity of
      rheumatoid arthritis (RA) that may have occurred during the 30 year period from
      1960 to 1990 in Japan. METHODS: Using records of patients diagnosed with RA from
      two hospitals, demographic and clinical features at initial visit were compared
      between two groups, one from 1960 to 1965 (group I) and the other from 1985 to
      1990 (group II). RESULTS: Mean age at the time of onset of the disease increased
      significantly from 37.5 years in group I to 46.9 in group II. The peak age at
      onset of RA shifted from the third to the fifth decade between group I and group
      II. There was no obvious change in morbidity as determined by seropositivity,
      rheumatoid nodules, and assessments of hip involvement. CONCLUSION: The age at
      onset of RA was delayed during a recent 30 year period in Japan. This increase in
      age at onset might result from environmental changes that occurred in Japan or
      may reflect a birth cohort phenomenon. Improvement of severity of disease was not
      found in this study.

PMID- 9175933
TI  - Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen.
AB  - OBJECTIVE: A 68k autoantigen has been identified by specific antibodies from
      patients with rheumatoid arthritis (RA). This study considered whether or not
      this antigen is a target for T cells and thus may play a part in T cell mediated
      immunopathology of active RA. METHODS: The 68k antigen was isolated and used in a
      nitrocellulose bound form to stimulate T cells. Proliferation of T lymphocytes of
      peripheral blood as well as synovial fluid was measured. RESULTS: Peripheral
      blood T cells specifically proliferating against the 68k antigen were detected in
      19 of 27 patients with RA (70%). For T cells isolated from peripheral blood,
      proliferation peaked on day 10. When T cells were isolated from actively inflamed
      synovial fluid, the proliferation kinetics shifted to a peak on day 3. Blockade
      of HLA class II antigens resulted in an increase of proliferation in the case of
      HLA-DP. Applying HLA-DP specific antibodies capable of inhibiting antigen
      presentation mediated by this molecule, T cells of 17 of 27 RA patients (63%)
      proliferated to a higher extent than with the 68k antigen alone. The phenomenon
      that an increased proliferation occurred upon blockade of a particular HLA class
      II family member was also demonstrated for DQ and DR: the 68k antigen likewise
      stimulated T cells restricted for DP or DQ, respectively. CONCLUSIONS: The novel
      68k antigen is a target of both T and B cellular immune responses and as such
      could play a part in the immune dysfunction of RA. The finding that blocking of
      certain HLA class II molecules functioning in antigen presentation (for example,
      via HLA-DQ) results in a higher instead of lower proliferation in vitro, may
      argue for the presence of antigen specific suppressive T cells.

PMID- 9175935
TI  - Prevalence of low body mass in rheumatoid arthritis: association with the acute
      phase response.
AB  - OBJECTIVE: To ascertain the prevalence of low body mass in a rheumatoid arthritis
      (RA) population and to explore a possible relation with the acute phase response.
      METHODS: 97 patients who fulfilled the American College of Rheumatology (ACR)
      criteria for RA were recruited. Change in weight from initial presentation was
      noted. Body mass index (BMI), upper arm fat and muscle areas were recorded
      together with fat free mass calculated from the waist measurement. Blood samples
      were taken for erythrocyte sedimentation rate (ESR), C reactive protein (CRP),
      and serum albumin. RESULTS: 13% of the RA group fell into the lowest 5th centile
      for BMI for the general population. The loss of body mass was greater for lean
      tissue than fat, with over 50% of the RA group falling into the lowest 10th
      centile of a reference population for the upper arm muscle area. Female patients
      who lost greater than 15% of their initial weight had higher health assessment
      questionnaire (HAQ) results than the rest of the group (p = 0.020). In female
      patients there was a significant correlation between reduced fat free mass and
      the acute phase response (ESR p = 0.016 and CRP p = 0.003) CONCLUSIONS: There is
      an increased prevalence of low body mass, greatest for lean tissue, in the RA
      population. In the female group there was an inverse relation between the acute
      phase response and fat free mass. Female patients with RA who lose a significant
      amount of weight are more disabled as assessed by HAQ.

PMID- 9175934
TI  - Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding
      the diagnosis of rheumatoid arthritis and systemic lupus erythematosus.
AB  - OBJECTIVES: Because oxidative damage has been implicated in the pathogenesis of
      rheumatoid arthritis and systemic lupus erythematosus, this study was designed to
      see if serum concentrations of alpha tocopherol, beta carotene, and retinol,
      substances believed to be involved in the prevention or repair of oxidative
      damage, might be lower among persons who develop rheumatoid arthritis or systemic
      lupus erythematosus than among those who do not. METHODS: For this prospective
      case-control study, persons with rheumatoid arthritis and systemic lupus
      erythematosus that developed two to 15 years after donating blood for a serum
      bank in 1974 were designated as cases. For each case, four controls were selected
      from the serum bank donors, matched for race, sex, and age. Stored serum samples
      from cases and controls were assayed for alpha tocopherol, beta carotene, and
      retinol. RESULTS: Cases of both diseases had lower serum concentrations of alpha
      tocopherol, beta carotene, and retinol in 1974 than their matched controls. For
      rheumatoid arthritis, the difference for beta carotene (-29%) was statistically
      significant. CONCLUSIONS: These findings support those of a previous study that
      low antioxidant status is a risk factor for rheumatoid arthritis. They suggest a
      similar association for systemic lupus erythematosus.

PMID- 9175936
TI  - Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and
      systemic lupus erythematosus as an index of an increased nitric oxide synthase
      activity.
AB  - OBJECTIVES: To determine the feasibility of monitoring the serum concentration of
      NG-hydroxy-L-arginine (L-NHA) as an index of an increased nitric oxide (NO)
      synthase activity in patients with rheumatoid arthritis (RA) and systemic lupus
      erythematosus (SLE) compared with nitrate (NO3-), the major circulating
      metabolite of NO whose concentration is influenced by dietary intake. METHODS:
      The serum concentrations of L-NHA, L-arginine (L-Arg), and NO3- were determined
      in 33 patients with RA, 25 patients with SLE and, 29 healthy subjects. RESULTS:
      Serum L-NHA was significantly increased in RA patients with high disease activity
      (287% of control, p < 0.01), but not with low disease activity (115%), as well as
      in patients with SLE (173%, p < 0.01). In contrast, serum NO3- did not differ
      significantly between either group of patients and the respective control group.
      CONCLUSION: NO synthase activity or expression, or both, is upregulated in RA
      patients with high disease activity and in patients with SLE. Serum L-NHA seems
      to be a more specific and reliable index of an increased activity of this enzyme
      in patients with acute or chronic inflammatory diseases than NO3-.

PMID- 9175937
TI  - Subgroups of primary Sjogren's syndrome. Sjogren's syndrome in male and
      paediatric Greek patients.
AB  - OBJECTIVES: To describe the clinical and serological findings in male and
      paediatric Sjogren's syndrome (SS) patients. PATIENTS AND METHODS: Using the
      European criteria for the diagnosis of SS 12 male and 13 paediatric patients were
      identified and compared with those of 30 consecutive unselected adult female SS
      patients. RESULTS: The mean (SD) age of paediatric patients was 9.4 (2.2) years,
      ranging from 6 to 14 years. Recurrent parotid gland enlargement was the initial
      clinical manifestation in the majority of the children with a statistical
      significance compared with male (p < 0.01) and with female patients (p < 0.0001).
      Sicca manifestations were the most common clinical symptoms in male and female
      patients at disease onset. The systemic manifestations were similar among the
      three groups except that men showed lower frequency of arthritis (p < 0.05) and
      Raynaud's phenomenon (p < 0.05) compared with women. No differences were found
      among the immunological profile of children and female patients, while male
      patients had a lower frequency of antinuclear antibodies (p < 0.025) and
      antibodies to Ro(SSA) nuclear antigens (p < 0.025) compared with women.
      CONCLUSION: Primary SS is rare in children and men in Greece. Recurrent parotid
      gland enlargement is the most common clinical finding at disease onset in
      children. Male patients seem to have less systemic manifestations and lower
      frequency of autoantibodies.

PMID- 9175938
TI  - Pigmented villonodular synovitis.

PMID- 9175939
TI  - Combination DMARD therapy for rheumatoid arthritis. Full or low DMARD doses?

PMID- 9175940
TI  - Tissue crosslinks concentrations in normal joints and chronic articular diseases.

PMID- 9175941
TI  - Obtaining informed consent for neonatal randomised controlled trials--an
      "elaborate ritual"?

PMID- 9175942
TI  - Comparison of mortality risk: a score for very low birthweight infants.
AB  - AIM: To develop and evaluate a score which quantifies mortality risk in very low
      birthweight (VLBW) infants (birthweight below 1500 g) at admission to the
      neonatal intensive care unit. METHODS: Five hundred and seventy two VLBW infants
      admitted from 1978 to 1987 were randomly assigned to a cohort (n = 396) for score
      development and a cohort (n = 176) for score validation. Two hundred and ninety
      four VLBW infants admitted from 1988 to 1991 were used to compare risk adjusted
      mortality between the two eras. RESULTS: Using multiple regression analysis,
      birthweight, Apgar score at 5 minutes, base excess at admission, severity of
      respiratory distress syndrome, and artificial ventilation were predictive of
      death in the development cohort. According to regression coefficients, a score
      ranging from 3 to 40 was developed. At a cutoff of 21, it predicted death in the
      validation cohort with a sensitivity of 0.85, a specificity of 0.73, and a
      correct classification rate of 0.76. The area under the receiver operating
      characteristic curve was 0.86. There was no significant difference in risk
      severity and in risk adjusted mortality between the eras 1978-87 and 1988-91.
      CONCLUSION: The present score is robust, easily obtainable at admission, and
      permits early randomisation based on mortality risk.

PMID- 9175943
TI  - Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term
      and preterm infants.
AB  - Urinary 5-L-oxoproline was measured in term and preterm infants from shortly
      after birth until 6 weeks of postnatal age to determine their ability to
      synthesise glycine. In term infants the excretion was five to 10 times that seen
      in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours
      after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a
      significant inverse linear correlation between the excretion of 5-L-oxoproline
      and length of gestation or birthweight. By 6 weeks of age there was no longer a
      significant difference in 5-L-oxoproline between term and preterm infants. There
      was no difference in the excretion of 5-L-oxoproline between boys and girls, or
      between infants fed on human milk or an artificial formula. If, in part,
      variability in the excretion of 5-L-oxoproline is determined by the extent to
      which the endogenous formation of glycine is adequate, then glycine formation may
      be marginal during early life, more so in preterm than in term infants, providing
      additional evidence that glycine is a conditionally essential amino acid in the
      neonate.

PMID- 9175944
TI  - Role of epidermal growth factor and transforming growth factor alpha in the
      developing stomach.
AB  - AIMS: To determine whether epidermal growth factor (EGF) or the related
      transforming growth factor alpha (TGF alpha) may have a role in the developing
      human stomach; to substantiate the presence of EGF in human liquor in the non
      stressed infant and whether EGF in amniotic fluid is maternally or fetally
      derived. METHODS: The temporal expression and localisation of EGF, TGF alpha, and
      their receptors during fetal and neonatal life were examined in 20 fetal and five
      infant stomachs. Simultaneously, samples of amniotic fluid and fetal urine from
      10 newborn infants were collected and assayed for EGF by radioimmunoassay.
      RESULTS: EGF immunoreactivity was not noted in any of the specimens examined. In
      contrast, TGF alpha immunoreactivity was shown in mucous cells from 18 weeks of
      gestation onwards. EGF receptor immunoreactivity was seen on superficial mucous
      cells in gastric mucosa from 18 weeks of gestation onwards. The median
      concentration of EGF was 30 and 8.5 pg/ml in amniotic fluid and fetal urine,
      respectively, suggesting that EGF is not produced by the fetus. CONCLUSIONS: This
      study adds weight to the hypothesis that swallowed EGF, probably produced by the
      amniotic membranes, and locally produced TGF alpha, may have a role in the growth
      and maturation of the human stomach.

PMID- 9175945
TI  - Neonatal symptomatic thromboembolism in Germany: two year survey.
AB  - AIMS: To determine the incidence of neonatal thromboembolism in Germany. METHODS:
      Diagnostic imaging techniques, therapeutic modalities, and short term outcome
      were evaluated in a prospective nationwide two year case registry study. RESULTS:
      The reported incidence of symptomatic neonatal thromboembolism, diagnosed in most
      cases with Doppler ultrasonography, was 5.1 per 100000 births, with a total of 79
      cases registered: renal venous thrombosis (n = 35); venous thrombosis (n = 25);
      and arterial vascular occlusion (n = 19). Fifty seven of 79 thromboses were
      associated with additional risk factors (central line n = 25, asphyxia n = 13,
      septicaemia n = 11, dehydration n = 6, maternal diabetes n = 2, cardiac disease n
      = 1). Inherited thrombophilia was also diagnosed in seven out of 35 cases
      investigated. Twenty three children received supportive treatment: 42 received
      heparin and in 13 neonates thrombolytic agents were administered. Most neonates
      (91%) survived; seven died. CONCLUSION: Controlled multicentre studies are needed
      to obtain more information on treatment efficacy.

PMID- 9175946
TI  - Light reduction and the electroretinogram of preterm infants.
AB  - AIMS: To examine the effects of light on retinal development and function in
      preterm infants as measured by the electroretinogram (ERG). Secondary outcomes
      included visual acuity testing, the incidence of retinopathy of prematurity, and
      general wellbeing, reflected in feeding tolerance, rate of weight gain, and
      length of hospital stay. METHODS: Eligibility criteria for enrollment were
      birthweight < or = 1250 g and gestational age < or = 31 weeks. Sixty one infants
      were randomly allocated by 6 hours after birth to a control or treatment group
      which wore 97% light filtering goggles for a minimum of four weeks or until the
      infant reached 31 weeks postmenstrual age. RESULTS: There were no significant
      differences between the two groups in the numbers of electroretinograms performed
      at 36 weeks of postmenstrual age. Although the sample size was not large enough
      to exclude clinically important differences in secondary outcomes, no significant
      differences were observed between the groups in visual acuity testing at 4-6
      months corrected age, incidence of retinopathy of prematurity, weight gain, or
      length of stay. CONCLUSION: These data support the safety and feasibility of this
      intervention. A much larger study will be needed to determine whether light
      reduction to the eyes of very low birthweight infants will reduce the incidence
      of retinopathy of prematurity or enhance general well-being.

PMID- 9175947
TI  - Randomised trial of dopamine compared with hydrocortisone for the treatment of
      hypotensive very low birthweight infants.
AB  - AIM: To compare the efficacy of hydrocortisone with dopamine for the treatment of
      hypotensive, very low birthweight (VLBW) infants. METHODS: Forty infants were
      randomly allocated to receive either hydrocortisone (n = 21) or dopamine (n =
      19). RESULTS: All 19 infants randomised to dopamine responded; 17 of 21 (81%) did
      so in the hydrocortisone group. Three of the four non-responders in the
      hydrocortisone group had clinically significant left to right ductal shunting.
      The incidence of bronchopulmonary dysplasia, retinopathy of prematurity,
      intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent
      ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did
      not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated
      plasma cortisol activity, either before or after treatment, did not differ
      between the two groups of infants. Although a significant difference in efficacy
      between dopamine and hydrocortisone was not noted (P = 0.108), there were four
      treatment failures in the hydrocortisone group, compared with none in the
      dopamine group. CONCLUSION: Both hydrocortisone and dopamine are effective
      treatments for hypotension in very low birthweight infants.

PMID- 9175948
TI  - Treatment of patent ductus arteriosus with ibuprofen.
AB  - AIM: To evaluate the efficiency and side effects of ibuprofen for the early
      treatment of patent ductus arteriosus (PDA) and compare it with indomethacin.
      METHODS: Forty preterm infants with gestational ages of less than 33 weeks, with
      respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were
      randomly assigned at days 2 to 3 of life to receive either intravenous
      indomethacin 3 x 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 x 10
      mg/kg, followed by 5 mg/kg 24 and 48 hours later. RESULTS: PDA closed in 15 of 20
      patients from the indomethacin group (75%) and in 16 of 20 (80%) from the
      ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a
      second treatment with indomethacin and in five (three in the indomethacin group
      and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen
      patients had a better urinary output and showed no increase in serum creatinine
      concentrations compared with the indomethacin group. Ibuprofen was not associated
      with any other side effect. CONCLUSIONS: Ibuprofen treatment seems to be as
      efficient as indomethacin in closing PDA on the third day of life in preterm
      infants with respiratory distress syndrome and seems to have fewer renal side
      effects.

PMID- 9175949
TI  - Renal calcification in preterm infants: follow up at 4-5 years.
AB  - AIM: To determine the consequences of renal calcification in preterm infants.
      METHODS: A cohort of 11 preterm babies was studied at the age of 4 to 5 years.
      They had had renal calcification as neonates. Seventeen matched controls were
      also studied. Each child had a renal ultrasound scan, a calcium load test, and a
      desmopressin test for renal concentrating ability (RCA). The study group also had
      glomerular filtration rate (GFR) estimated, using the height:creatinine ratio,
      and tubular phosphate reabsorption, without phosphate load, per glomerular
      filtration rate (Tp/GFR) calculated, RESULTS: In the study group the median GFR
      was 61 ml/min/1.73m2 (range 46-79 ml/min/1.73m2) and the median calculated Tp/GFR
      SD score was -0.94 (range -2.8-0.68). Five children out of the study group had
      ultrasonic evidence of renal calcification. There was no significant difference
      between the two groups in renal size, calciuria, before or after calcium load, or
      RCA. Eight children (three patients, five controls) had an abnormal calcium load
      test. The RCA of the children in the study and control groups combined was below
      that of published values, with a median calculated SD score -0.71 (95% CI -1.21
      to -0.23). CONCLUSIONS: There was evidence of renal dysfunction in children who
      had been born preterm. Renal calcification detected in the neonatal period does
      not seem to be a major predisposing factor for the abnormalities of renal
      function subsequently observed in these infants.

PMID- 9175950
TI  - Randomised controlled double blind study of role of recombinant erythropoietin in
      the prevention of chronic lung disease.
AB  - AIM: To evaluate the role of recombinant human erythropoietin (R-HuEpo) in
      reducing iron infusion, which may exacerbate free radical damage, leading to
      chronic lung disease. METHODS: A multicentre, randomised, placebo controlled,
      double blind study was carried out in four neonatal intensive care units in
      Yorkshire. Infants were randomly allocated and received either R-HuEpo (480
      U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome
      measure was the number of days on respiratory support and a secondary outcome the
      number of blood transfusions required. RESULTS: Forty two very low birthweight
      (VLBW) infants were randomly allocated. There was little difference in the need
      for respiratory support one month after randomisation, but subsequently there was
      a trend towards a reduction in the proportion requiring respiratory support in
      the R-HuEpo group (difference at three months -0.50, 95% confidence interval 
      1.00, 0.17). During stay in hospital, the median number of blood transfusions was
      lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0).
      The study was stopped early because of failure to recruit babies at the expected
      rate. CONCLUSIONS: R-HuEpo seems to reduce the number of days in oxygen for ill
      VLBW infants. These data could be used to construct a larger multicentre study to
      evaluate this effect further.

PMID- 9175951
TI  - Capillary refilling time in newborn babies: normal values.
AB  - AIM: To assess the normal values of capillary refilling time (CRT) in healthy
      newborn babies; to assess the effect of different nursery containers (incubator,
      radiant warmer, crib), phototherapy, birthweight, gestational age, size for
      gestational age and sex on CRT; to compare CRT at different body sites as well as
      to assess the variation between observers. METHODS: Healthy neonates (n = 469) of
      different gestational ages and different sizes for gestational age, were studied
      1 to 7 days after birth. CRT was measured in four of the most suitable sites
      namely, midpoints of the sternum and the forehead, the palm of the hand and the
      plantar surface of the heel (defined as chest, head, palm and heel,
      respectively). The applied pressing time was 5 seconds. CRT was measured with a
      manual stopwatch. RESULTS: Only the chest and the head distribution curves
      followed the Gaussian curve. The mean values and standard deviation of CRT in all
      tested nursery containers, including phototherapy for the chest, ranged from 1.82
      (0.34) seconds to 2.01 (0.423) seconds, and for the head from 1.59 (0.36) seconds
      to 1.83 (0.31) seconds. The mean value of chest CRT was always longer than the
      head CRT for all parameters. Significant differences were found between different
      nursery containers, receivers, and non-receivers of phototherapy and between
      observers. No difference was found between sex, birthweight, gestational age and
      size for gestational age. CONCLUSIONS: The upper limit of normal for neonatal CRT
      was 3 seconds. Nursery containers, phototherapy, and observers produced
      significantly different results, but the differences were not clinically
      important. CRT values of the midpoints of the sternum and the forehead are the
      most consistent.

PMID- 9175952
TI  - Neonatal intensive care provision in the United Kingdom 1992-3. British
      Association of Perinatal Medicine.
AB  - Medical neonatal units in the United Kingdom were surveyed in 1994 to determine
      for 1992-3 the number of cots, medical and nursing staff, workload, the ability
      of units to retrieve data and to assess any changes that might have occurred
      since the NHS reforms. There was an 84% response rate. Many units were unable to
      provide workload and birthweight specific information. Cot occupancy, and there
      fore the exposure of individual neonatal nurses to babies requiring intensive
      care, increased in direct proportion to unit workload. In spite of this a third
      of all neonatal intensive care, even for babies of < 100 g, is provided by units
      with ventilator workloads of 50 or fewer babies a year. There was a 25% increase
      in intensive care level 1 (ICL1) cot provision between 1989 and 1993, but no
      change in the total number of cots. Consistent maintenance of a common dataset by
      all units undertaking neonatal intensive care would do much to assist future
      planning.

PMID- 9175953
TI  - Faecal chymotrypsin in small for gestational age infants: effects of nucleotides
      and breast feeding.
AB  - The effect of diet on pancreatic exocrine function, measured by faecal
      chymotrypsin activity (FCA), was studied longitudinally in three groups of small
      for gestational age (SGA) infants in the first six months of life. The three
      groups comprised breastfed infants (group B), those randomly allocated to receive
      a standard infant formula (group S), or the same formula supplemented with
      nucleotides (group N). The three groups did not differ in their birthweight or
      gestational age. Nucleotide supplementation of infant formula improves catchup
      growth in SGA infants but whether this is due to effects on the gastrointestinal
      mucosa or the exocrine pancreas is not known. There were no differences in FCA at
      study entry but by one month group B had significantly lower values than the
      other groups, and this was maintained at 2, 4, and 6 months. Groups N and S did
      not differ significantly at any time point. Nucleotide supplementation of infant
      formula does not influence pancreatic exocrine function and its effect on growth
      is unlikely, therefore, to be mediated through the pancreas. This study shows
      that breast feeding is associated with lower FCA which may be related to the
      lower protein content of human milk. Reliable interpretation of FCA in young
      infants requires information about their diet.

PMID- 9175954
TI  - Tracheobronchomalacia in preterm infants with chronic lung disease.
AB  - Tracheobronchomalacia is a treatable cause of persisting ventilatory requirements
      in the preterm neonate, and warrants a high index of suspicion. Five preterm
      infants with persisting ventilatory requirements with evidence of
      tracheobronchomalacia are reported. Four were diagnosed by tracheobronchogram and
      one by flexible endoscopy. All were successfully managed by continuous positive
      airway pressure (CPAP) via a tracheostomy. One infant died of unrelated causes.
      The oldest child in this series at the age of 2 years requires no further
      ventilatory support. Tracheobronchial anomalies should be considered in all
      preterm infants with persisting ventilatory requirements.

PMID- 9175955
TI  - Fat digestion in the neonate.

PMID- 9175956
TI  - Dr Percivall Willughby, MD (1596-1685): pioneer "man" midwife of Derby.

PMID- 9175957
TI  - Neural tube defects 1974-96: down but not out.

PMID- 9175958
TI  - Obstetric practices in the Bible.

PMID- 9175959
TI  - Effect of blood transfusion on postoperative immunocompetence.

PMID- 9175960
TI  - Extradural pain relief in labour: bupivacaine sparing by extradural fentanyl is
      dose dependent.
AB  - The minimum local analgesic concentration (MLAC) of bupivacaine in labour is
      defined as the effective concentration in 50% of subjects (EC50). We have used
      the technique of double-blinded sequential allocation to quantify the bupivacaine
      sparing effect of the addition of four different doses of extradural fentanyl in
      223 labouring women. There were five groups: (1) plain bupivacaine (control); (2)
      bupivacaine with fentanyl 1 microgram ml-1; (3) bupivacaine with fentanyl 2
      micrograms ml-1; (4) bupivacaine with fentanyl 3 micrograms ml-1; and (5)
      bupivacaine with fentanyl 4 micrograms ml-1. The MLAC of bupivacaine were 0.069%
      w/v, 0.057% w/v, 0.048% w/v, 0.031% w/v and 0.015% w/v, respectively. We observed
      a reduction in MLAC of 18%, 31% (P = 0.03%), 55% (P < 0.0001) and 72% (P <
      0.0001) with fentanyl 1, 2, 3 and 4 micrograms ml-1, respectively, demonstrating
      a significant negative linear trend (P < 0.0001) with increasing fentanyl dose.
      The incidence of pruritus was increased significantly with fentanyl 4 micrograms
      ml-1 (P = 0.0015). Because of this, fentanyl 3 micrograms ml-1 may be the optimal
      dose when the aim is bupivacaine sparing extradural analgesia during labour.

PMID- 9175961
TI  - Combined spinal-extradural anaesthesia for preterm and term caesarean section: is
      there a difference in local anaesthetic requirements?
AB  - In a non-blinded observational study, we have tested the null hypothesis that
      there is no difference in local anaesthetic requirements for subarachnoid
      anaesthesia between women presenting for Caesarean section at term or preterm (38
      42 and 28-35 weeks' gestation, respectively). Using a combined spinal-extradural
      technique, 2.25 ml of 0.5% hyperbaric bupivacaine was given, in the sitting
      position, to 50 women presenting for Caesarean section. In 21 of 25 preterm
      women, adequate sensory block for surgery did not develop (P < 0.001) and they
      required supplementary extradural local anaesthetic (median 8 ml of 2% lignocaine
      with 1:200,000 adrenaline (interquartile range 4-12 ml)); preterm women not
      requiring extradural supplementation were at the upper end of the gestational
      range. There was a strong linear correlation between increasing gestation and
      block height in the preterm group (Spearman rank correlation coefficient = 0.74;
      95% confidence intervals 0.49, 0.88). All women in the term group developed
      adequate anaesthesia with the subarachnoid dose alone. Onset of anaesthesia was
      slower in the preterm group (median 15 vs 5 min) with a lower incidence of
      hypotension (P = 0.0005).

PMID- 9175962
TI  - Effect of lignocaine and pH on propofol-induced pain.
AB  - Propofol has the disadvantage of pain on injection. A higher partition of
      propofol in the aqueous phase of the preparation causes a higher incidence of
      pain on injection while addition of 1% lignocaine to propofol reduces pain. The
      low concentration of this local anaesthetic and the rapid pain relief observed
      indicates that mechanisms other than local anaesthesia are involved, that is
      change in pH. We performed a clinical study to investigate the influence of
      lignocaine and pH on pain during injection of 1% Diprivan. Ten parts of 1%
      Diprivan were mixed with one part of saline, 1% lignocaine or hydrochloric acid
      to achieve the same pH as that after addition of lignocaine. Diprivan 1% mixed
      with 1% lignocaine and with hydrochloric acid gave mean pain ratings (1-10) of
      0.32 (SD 0.75) (n = 25) and 0.88 (1.30) (n = 24), respectively. These ratings
      were significantly lower than ratings after injection of a saline-Diprivan
      mixture (2.18 (2.06), n = 22). The pH of the 1% Diprivan formulation decreased
      after mixing with 1% lignocaine. The concentration of propofol in the aqueous
      phase was lower when 1% Diprivan was mixed with 1% lignocaine (0.376 g litre-1)
      or HCl (0.392 g litre-1) compared with 1% Diprivan and saline (0.476 g litre-1)
      mixed in the same proportion. Thus pH changes may modify propofol-induced pain on
      injection by a mechanism different from the effect of the local anaesthetic on
      the vascular endothelium. Our findings may explain why lignocaine mixed with
      propofol causes less pain than injection of lignocaine followed by propofol.

PMID- 9175963
TI  - Central nervous and cardiovascular effects of i.v. infusions of ropivacaine,
      bupivacaine and placebo in volunteers.
AB  - We have compared the incidence of CNS symptoms and changes in echocardiography
      and electrophysiology during i.v. infusions of ropivacaine, bupivacaine and
      placebo. Acute tolerance of i.v. infusion of 10 mg min-1 was studied in a
      crossover, randomized, double-blind study in 12 volunteers previously acquainted
      with the CNS effects of lignocaine. The maximum tolerated dose for CNS symptoms
      was higher after ropivacaine in nine of 12 subjects and higher after bupivacaine
      in three subjects. The 95% confidence limits for the difference in mean dose
      between ropivacaine and bupivacaine were -30 and 7 mg. The maximum tolerated
      unbound arterial plasma concentration was twice as high after ropivacaine (P <
      0.001). Muscular twitching occurred more frequently after bupivacaine (P < 0.05).
      The time to disappearance of all symptoms was shorter after ropivacaine (P <
      0.05). A threshold for CNS toxicity was apparent at a mean free plasma
      concentration of approximately 0.6 mg litre-1 for ropivacaine and 0.3 mg litre-1
      for bupivacaine. Bupivacaine increased QRS width during sinus rhythm compared
      with placebo (P < 0.001) and ropivacaine (P < 0.01). Bupivacaine reduced both
      left ventricular systolic and diastolic function compared with placebo (P < 0.05
      and P < 0.01, respectively), while ropivacaine reduced only systolic function (P
      < 0.01).

PMID- 9175964
TI  - Assessment of cardiovascular changes during laparoscopic hernia repair using
      oesophageal Doppler.
AB  - We have used an oesophageal Doppler to measure aortic blood flow velocity before,
      during and after induction of carbon dioxide pneumoperitoneum in 10 consecutive
      patients, mean age 58 yr, undergoing laparoscopic hernia repair. Derived values
      for stroke distance, minute distance and systemic vascular resistance showed
      considerable interpatient variation indicating unpredictable haemodynamic
      responses. Five minutes after insufflation of the abdomen there was a significant
      increase in mean arterial pressure from 82.5 to 103.6 mm Hg (P < 0.05) but both
      stroke distance and minute distance decreased significantly (mean 12.0 (SEM 1.4)
      cm to 9.0 (0.7) cm, P < 0.05; and 747.5 (82) cm min-1 to 596 (49) cm min-1, P <
      0.05; respectively) indicating a significant decrease in cardiac output. There
      was a corresponding increase in the index of systemic vascular resistance from
      1092 (747) to 2079 (400) (P < 0.05) which persisted after deflation of the
      abdomen. Oesophageal Doppler can provide continuous online haemodynamic data with
      a rapid response to acute changes and may have a role in non-invasive
      haemodynamic monitoring during laparoscopic procedures in older patients with
      cardiovascular disease.

PMID- 9175965
TI  - Transcranial cytokine gradients in patients requiring intensive care after acute
      brain injury.
AB  - After acute brain injury there may be increased intracranial production of
      cytokines, with activation of inflammatory cascades. We have sought to determine
      if a transcranial cytokine gradient was demonstrable in paired sera of 32
      patients requiring intensive care after acute brain injury. The difference
      between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous
      and arterial serum was measured on admission, and at 24, 48 and 96 h after the
      primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but
      median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the
      traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups,
      respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This
      suggests that there is significant production of IL-6 by intracranial cells after
      acute brain injury. Therapy directed towards combatting the negative effects of
      IL-6 may potentially benefit patients who have sustained an acute brain injury.

PMID- 9175966
TI  - Ketamine increases the amplitude of the 40-Hz auditory steady-state response in
      humans.
AB  - The auditory middle latency response (AMLR) and the 40-Hz auditory steady-state
      response (40-Hz ASSR) are evoked potentials which possibly arise from the same
      generators in the primary auditory cortex. Both responses are attenuated by most
      general anaesthetics. Ketamine, however, has been reported to have no effect on
      the AMLR. Our aim was to evaluate the effects of ketamine on the 40-Hz ASSR.
      Spectral analysis of the electroencephalogram (EEG) was also conducted to
      independently examine the effects of ketamine. Ketamine 1.5 mg kg-1 was given to
      12 patients for induction of general anaesthesia. Recordings of the 40-Hz ASSR
      and EEG were obtained every minute from 3 min before administration of ketamine
      to 5 min after injection, when the study was terminated. Similar recordings were
      obtained in three control subjects under identical conditions except that no
      medication was administered. Consciousness, defined as responsiveness to verbal
      commands, was assessed before each recording. Ketamine caused an increase in the
      amplitude of the 40-Hz ASSR (P < 0.01). Using published AMLR data, we conducted a
      simulation experiment that suggested that the effect of ketamine on the AMLR can
      explain its effects on the amplitude of the 40-Hz ASSR. There was a pronounced
      increase in relative theta (3.9-7.9 Hz) EEG power and a decrease in relative
      alpha (8.0-12.8 Hz) power (P < 0.001). These changes were not observed in the
      control group. Ketamine produced unconsciousness until the end of the study in
      five patients and transient unconsciousness in five patients. Two patients did
      not lose consciousness after administration of ketamine. The 40-Hz ASSR and EEG
      revealed no consistent differences between conscious and unconscious patients. No
      relationship could be demonstrated between the increase in amplitude of the 40-Hz
      ASSR or of relative theta power (the hallmark of ketamine effect) and loss of
      responsiveness to commands. We conclude that ketamine, unlike other anaesthetics,
      increases the amplitude of the 40-Hz ASSR.

PMID- 9175967
TI  - Effects of inotropes on human leucocyte numbers, neutrophil function and
      lymphocyte subtypes.
AB  - We have investigated the effects of inotropes with different adrenergic receptor
      specificity on differential white cell count, lymphocyte subtypes and neutrophil
      function in healthy volunteers. Six healthy, male volunteers were enrolled into
      this randomized, placebo-controlled pilot study. Each volunteer was studied on
      four separate occasions during a 2-h infusion of various agents, and for 2 h
      after stopping the infusion. The agents investigated were adrenaline 0.1
      microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms
      kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120
      and 240 min. Haemodynamic monitoring was continued throughout the study. Full
      blood count, white cell differential count and enumeration of lymphocyte subtypes
      were performed. Neutrophil function tests included chemoluminescence, and
      assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon
      signed rank test was used to compare differences between placebo and active drugs
      at each time compared with baseline. There was a significant increase in white
      cell count, lymphocyte count and neutrophil count with adrenaline, and a small
      but significant decrease in these variables with dobutamine and dopexamine. These
      changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts.
      Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine
      increased significantly only with adrenaline at 30 min (P = 0.046). There were no
      other significant changes in tests of neutrophil function. Infusion of inotropes
      was associated with changes in white cell numbers, lymphocyte subtypes and
      neutrophil respiratory burst. In healthy volunteers, adrenaline had effects
      different from those of dobutamine and dopexamine. The clinical relevance of such
      effects requires further investigation in critically ill patients.

PMID- 9175968
TI  - Can prolonged expiration manoeuvres improve the prediction of arterial PCO2 from
      end-tidal PCO2?
AB  - We have studied, in 16 patients undergoing thoracoabdominal oesophagectomy, if
      two prolonged expiration manoeuvres improve prediction of arterial PCO2 (PaCO2)
      from end-tidal PCO2 (PE' CO2). PE' CO2, PCO2 at the end of a simple prolonged
      expiration (PE1 CO2), and PCO2 at the end of a prolonged expiration preceded by
      sustained hyperinflation of the lungs (PE2 CO2), were measured during laparotomy,
      in the lateral thoracotomy position during two-lung ventilation, and after
      transition to one-lung ventilation. (PaCO2-PE' CO2) was 1.3 (SD 0.4) kPa during
      laparotomy and this remained stable throughout the study. Both manoeuvres
      decreased the mean arterial to peak expired PCO2 difference, particularly during
      one-lung ventilation. However, PE1 CO2 and PE2 CO2 did not agree more closely
      with PaCO2 than PE' CO2 at any stage of the study. We conclude that these
      manoeuvres did not improve estimation of PaCO2 from PE' CO2.

PMID- 9175969
TI  - Inositol 1,4,5-trisphosphate in blood and skeletal muscle in human malignant
      hyperthermia.
AB  - The in vitro contracture test (IVCT) is the only available diagnostic method at
      present for evaluation of malignant hyperthermia (MH) susceptibility. However,
      the disadvantage of the IVCT is that it is invasive. Several studies suggest that
      an altered inositol phosphate system is involved in the development of MH. A
      greater concentration of inositol 1,4,5-trisphosphate (1,4,5-IP3) was found in MH
      susceptible (MHS) than in normal (MHN) skeletal muscles. In this study the
      concentrations of 1,4,5-IP3 in blood samples and skeletal muscle specimens of
      identical patients were measured in an attempt to define susceptibility to MH.
      Muscle biopsies were obtained from 34 patients with clinical suspicion of MH.
      Patients were first classified as MHS (n = 19), MHN (n = 8) or MH equivocal (MHE;
      n = 7) by the standard IVCT. For detection of 1,4,5-IP3 concentrations, blood
      samples were obtained and an additional muscle specimen was excised. After sample
      preparation, concentrations of 1,4,5-IP3 were measured using radioimmunoassay. In
      blood samples, concentrations of 1,4,5-IP3 were similar in all individuals tested
      for MH susceptibility and in control patients not tested for MH susceptibility (n
      = 44). In skeletal muscle, 1,4,5-IP3 concentrations were significantly higher in
      MHS than in MHE or MHN patients, respectively. Each MHS sample contained more
      1,4,5-IP3 than the highest concentration measured in MHN muscle. Defining
      arbitrary thresholds for 1,4,5-IP3 concentration in skeletal muscles in order to
      discriminate between MHS and MHN status, it was possible to assign three MHE
      patients to MHS and four to MHN. This study supports the hypothesis that an
      altered inositol phosphate system might be involved in MH. However, measurement
      of 1,4,5-IP3 concentration in a simple blood sample preparation is not reliable
      for MH susceptibility screening.

PMID- 9175971
TI  - Responses to simulated anaesthetic emergencies by anaesthetists with different
      durations of clinical experience.
AB  - We have compared the responses of four groups of anaesthetists, with different
      durations of clinical experience, to nine different simulated emergencies. Five
      anaesthetists in each group completed each of the nine simulated emergencies.
      Anaesthetists with less than 1 yr experience performed less well than the three
      other groups of anaesthetists (chi-square, P < 0.02). However, all groups made
      serious errors in both diagnosis and treatment, and accepted treatment guidelines
      were not followed. We have shown that a simple, inexpensive simulator can be used
      to evaluate the performance of anaesthetists of different durations of clinical
      experience.

PMID- 9175970
TI  - Leucocyte-derived bioactive substances in fresh frozen plasma.
AB  - Bioactive substances in fresh frozen plasma (FFP) are considered to be related to
      adverse reactions after transfusion, particularly in septic or traumatized
      patients. Therefore, we analysed the concentration of various bioactive
      substances (histamine, eosinophil cationic protein, eosinophil protein X,
      myeloperoxidase and interleukin-6) in 25 u. of thawed FFP from healthy donors.
      These were compared with donor plasma concentrations of 24 healthy controls. In
      addition, we analysed the concentration of the bioactive substances, except
      interleukin-6, in 25 u. of thawed FFP, which were subjected to leucocyte
      filtration before freezing and storage. Finally, we analysed the substances in 10
      leucocyte non-filtered plasma units before freezing and storage, and after
      thawing, respectively. Before analyses, which were performed by ELISA and RIA
      methods, these latter samples were sterile filtered through a 0.20-micron filter.
      Histamine, eosinophil cationic protein, eosinophil protein X and myeloperoxidase
      concentrations were significantly greater (P < 0.05) in the 25 u. of FFP compared
      with normal donor plasma. Pre-storage leucocyte filtration reduced concentrations
      of the bioactive substances in FFP to concentrations comparable with normal donor
      plasma concentrations. Interleukin-6 was undetectable in all FFP units and in 21
      of the 24 control donors. Histamine, eosinophil cationic protein and
      myeloperoxidase concentrations were significantly higher (P < 0.05) in samples
      collected from the 10 u. of FFP after freezing and thawing compared with samples
      collected before freezing. We conclude that fresh frozen plasma prepared by a
      conventional separation method contains various leucocyte-derived bioactive
      substances, which may be reduced by pre-storage leucocyte filtration.

PMID- 9175972
TI  - Leakage of fluid past the tracheal tube cuff in a benchtop model.
AB  - We have assessed a range of high volume, low pressure (HVLP) cuffed tracheal
      tubes in a benchtop model, for leakage of fluid from above the cuff to the model
      trachea below, during various ventilatory modes. Rapid leakage occurred in the
      model during all modes of ventilation, unless tracheal pressure was greater than
      the height of fluid in the column above the cuff. This leakage occurred
      preferentially down longitudinal folds that occur in the HVLP cuff wall. This
      model suggests that, if a longitudinal fold within the cuff wall is patent, then
      the possibility exists of subglottic to tracheal leakage.

PMID- 9175973
TI  - 5-HT spinal antinociception involves mu opioid receptors: cross tolerance and
      antagonist studies.
AB  - The antinociceptive effects of intrathecal 5-HT, fentanyl, ICI197067 and U50488H
      were assessed by electrical current nociceptive threshold and tail flick latency
      measurements. Equieffective doses of these agonists were then given intrathecally
      with a range of doses of naloxone or the highly selective mu opioid antagonist,
      beta-funaltrexamine. Antagonist dose-response curves were plotted. Other rats
      were made tolerant to either fentanyl or 5-HT by intrathecal injections of these
      drugs seven times daily and the antinociceptive effects of intrathecal fentanyl
      and 5-HT were assessed in each group. All intrathecal drugs caused spinally
      mediated antinociception in both tests. The antinociceptive effects of
      intrathecal 5-HT assessed by the electrical test (ECT) but not by tail flick
      latency (TFL) were suppressed by both opioid antagonists at doses similar to
      those required to suppress all of the effects of intrathecal fentanyl. The ED50
      values were 0.22 (fentanyl, ECT), 0.25 (fentanyl, TFL) and 0.18 (5-HT, ECT) mumol
      kg-1 for naloxone and for beta-funaltrexamine 2.2 fmol (5-HT, ECT), the same
      order as that required to produce similar suppression of the antinociceptive
      effects of fentanyl (46 amol: fentanyl, ECT; 4.6 fmol: fentanyl, TFL) and very
      different from the ED50 for beta-FNA suppression of the antinociceptive effects
      of the kappa opioid, U50488H (5.88 pmol). Cross tolerance in both directions was
      demonstrated between intrathecal fentanyl and 5-HT in the electrical test but not
      in the tail flick test. We conclude that intrathecal 5-HT caused spinally
      mediated antinociceptive effects revealed by electrical current and tail flick
      latency tests. The antinociceptive effects in the electrical test involved spinal
      cord mu opioid receptors.

PMID- 9175974
TI  - Haemodynamic conditions enhancing gas embolism after venous injury during
      laparoscopy: a study in pigs.
AB  - This study was designed to determine the conditions that promote carbon dioxide
      embolism after venous injury during laparoscopy in pigs. Injury to an iliac vein
      was filmed during laparoscopy in the presence of a pneumoperitoneum created at
      increasing pressures from 0 to 30 mm Hg in 5-mm Hg increments. At intraperitoneal
      pressures less than 20 mm Hg, there was a parallel increase in femoral venous
      pressures, resulting in haemorrhage, with persistent blood flow to the inferior
      vena cava. At intraperitoneal pressures of 20-30 mm Hg, there was collapse of the
      femoral vein, occurring earlier in the presence of hypovolaemia. Between these
      two states (haemorrhage and collapse), there was a point of equilibrium which
      allowed retrograde venous penetration of carbon dioxide bubbles. During release
      of the pneumoperitoneum, these bubbles were exteriorized through the area of the
      injury, but some passed into the inferior vena cava where their presence was
      detected by an oesophageal Doppler probe.

PMID- 9175975
TI  - Increased intraperitoneal pressure up to 15 mm Hg does not reliably induce
      haemodynamic changes in pigs.
AB  - Haemodynamic alterations occur consistently with laparoscopic surgery in humans.
      These haemodynamic changes have never been reproduced in an animal model without
      additional potentiating factors. As these alterations may be deleterious in some
      patients and as the cause is only partly understood, we have used an animal model
      to study these changes. Pneumoperitoneum with intraperitoneal pressures of up to
      15 mm Hg were produced in pigs, in the same way as for laparoscopic surgery in
      humans. Arterial pressure, cardiac output, pulmonary arterial pressure and
      systemic arterial resistance were assessed at baseline and after pneumoperitoneum
      had been produced. Intraperitoneal pressures of up to 15 mm Hg were not
      associated with consistent circulatory changes and we conclude that haemodynamic
      changes associated with laparoscopic surgery are dependent on species.

PMID- 9175976
TI  - In vivo assessment of droperidol-induced bronchial relaxation in dogs using a
      superfine fibreoptic bronchoscope.
AB  - Droperidol has been reported to cause bronchodilatation but its mechanism(s) of
      action is unknown. We have evaluated the spasmolytic effect of droperidol on
      histamine- and serotonin (5-HT)-induced bronchoconstriction in dogs. Bronchial
      cross-sectional area was assessed with a superfine fibreoptic bronchoscope.
      Twenty-eight mongrel dogs were allocated randomly to one of two groups (histamine
      and 5-HT) to receive either histamine or 5-HT to induce bronchoconstriction.
      Changes in bronchial cross-sectional area were presented as percentage of basal
      bronchial cross-sectional area. Continuous i.v. infusion of histamine 500
      micrograms kg-1 h-1 or 5-HT 500 micrograms kg-1 h-1 decreased percentage
      bronchial cross-sectional area by 46.4 (14.3)% or 68.9 (13.7)%, respectively. In
      both groups, droperidol reversed bronchoconstriction in a dose-dependent manner.
      In the histamine but not in the 5-HT group, plasma adrenaline and noradrenaline
      concentrations increased significantly after i.v. droperidol. In addition,
      propranolol antagonized droperidol-induced relaxation in the histamine but not in
      the 5-HT group. Our data indicate that the spasmolytic effect of droperidol on
      canine airway was caused, at least in part, by both catecholamine releases and 5
      HT receptor antagonism.

PMID- 9175977
TI  - Measurement of bronchodilatation using a superfine fibreoptic bronchoscope.
AB  - In this study, we report the development and accuracy of a direct technique to
      measure airway calibre using a superfine fibreoptic bronchoscope. Ten mongrel
      dogs were anaesthetized with pentobarbitone and the trachea intubated with a
      tracheal tube; the small lumen of the tube allowed passage of a superfine
      fibreoptic bronchoscope (od 2.2 mm). Bronchial cross-sectional area and airway
      pressure were recorded continuously and dynamic pulmonary compliance and airway
      resistance calculated. The dogs were allocated to one of two groups. In the first
      group (six dogs), bronchoconstriction was induced with histamine 10 micrograms kg
      1 i.v. and 500 micrograms kg-1 h-1 c.i.v. Thirty minutes later, adrenaline 0-0.4
      mg kg-1 was given i.v. Bronchial cross-sectional area, dynamic pulmonary
      compliance and airway resistance were assessed simultaneously. In the second
      group, 0.9% saline was given 30 min after placement of the superfine fibreoptic
      bronchoscope and 10 min later atropine 0.1 microgram kg-1 was administered. In
      the first group, histamine decreased mean percentage bronchial cross-sectional
      area by 49.2 (SD 11.5) %, reduced dynamic pulmonary compliance from 32.1 (12.6)
      to 22.3 (5.2) ml cm H2O-1 and increased airway resistance from 39.1 (11.6) to
      57.2 (10.2) cm H2O litre-1 s-1. Adrenaline produced a dose-dependent increase in
      percentage bronchial cross-sectional area and dynamic pulmonary compliance to
      119.4 (31.3)% and 27.4 (5.5) ml cm H2O-1, respectively, and a decrease in airway
      resistance to 43.9 (7.2) cm H2O litre-1 s-1. There were significant correlations
      between percentage bronchial cross-sectional area and dynamic pulmonary
      compliance (r = 0.720, P < 0.0001) and airway resistance (r = 0.727, P < 0.0001).
      Atropine 0.1 mg kg-1 increased basal bronchial cross-sectional area to 137.5
      (16.9) %. These data indicate that adrenaline reversed histamine- and
      pentobarbitone-induced bronchoconstriction.

PMID- 9175978
TI  - Cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1 in
      anaesthetized patients, paralysed with vecuronium.
AB  - We have studied, in adult patients, ASA I-II, the cardiovascular effects of an
      intubating dose of rocuronium 0.6 mg kg-1. After induction, patients were
      paralysed with vecuronium and the trachea intubated. Heart rate (HR) and non
      invasive mean arterial pressure (MAP) were measured every 1 min. After
      stabilization of HR and MAP, defined as < 3% change over three measurements,
      rocuronium (n = 20) or saline (n = 10) was injected at random. Mean HR increased
      initially from 66.6 to 72.1 beat min-1, 4 min after rocuronium, and then
      decreased gradually to 69.6 beat min-1, that is a net increase of 3.3 beat min-1
      over 10 min (P < 0.001), whereas after saline there was a gradual decrease from
      65.8 to 60.9 beat min-1 (P < 0.001) over 10 min. From the third minute, HR was
      significantly higher in the rocuronium group. Mean MAP decreased in both groups
      within 10 min to a similar extent after rocuronium and saline, that is from 74.9
      to 72.1 mm Hg and from 74.7 to 72.2 mm Hg, respectively (both P < 0.001). There
      were no differences in MAP at any time between the rocuronium and saline groups.
      We conclude that an intubating dose of rocuronium, in the absence of haemodynamic
      effects related to paralysis itself, resulted in a limited increase in HR without
      change in MAP, probably because of its weak vagolytic activity.

PMID- 9175979
TI  - Changes in extracellular brain ascorbate in rat striatum in response to
      administration of non-volatile anaesthetic agents.
AB  - We used constant potential in vivo voltammetry to measure changes in striatal
      ascorbate in the rat in response to i.p. administration of several non-volatile
      anaesthetics. Propofol and pentobarbitone, which enhance GABA-mediated neuronal
      inhibitions, decreased ascorbate current to 27.0 (SEM 7.4) % and 46 (6) % of
      control, respectively. Chloral hydrate, diazepam alone or with ketamine, and
      fentanyl-fluanisone with midazolam produced no changes in ascorbate current.

PMID- 9175980
TI  - Conservative management of extradural abscess complicating spinal-extradural
      anaesthesia for caesarean section.
AB  - We report a case of lumbar extradural abscess that presented 9 days after an
      elective Caesarean section performed under combined spinal-extradural
      anaesthesia. This was successfully treated conservatively with full recovery. The
      clinical course included development, and then resolution, of mild paraparesis.
      Conservative treatment of an extradural abscess in the obstetric population has
      not been described previously.

PMID- 9175981
TI  - KTP laser-resistant properties of the reinforced laryngeal mask airway.
AB  - We have assessed, in vitro, the effect of KTP laser strike on the reinforced
      laryngeal mask airway (RLMA) under a variety of conditions. At power densities
      normally encountered in clinical practice, using a divergent KTP laser beam, the
      RLMA could not be penetrated and did not ignite with laser strike. The RLMA was
      penetrated at a high power density of 6.94 W mm-2 after 45-60 s. A flame appeared
      over the RLMA shaft at this power density after 12-35 s. The black marker line on
      the RLMA shaft was somewhat more vulnerable to the effects of laser strike. The
      flow of oxygen and nitrous oxide within the shaft did not appreciably alter the
      laser-resistant properties of the RLMA. The RLMA cuff was more vulnerable to
      laser strike than was the shaft and was penetrated at very low power densities.
      Filling the cuff with saline had a protective effect and penetration did not
      occur at power densities which caused penetration of air-filled cuffs (0.37 W mm
      2).

PMID- 9175982
TI  - Calculation of drug dosage and body surface area of children.
AB  - The British National Formulary and many reference textbooks recommend that drug
      dosages for children be calculated according to body surface area (BSA). Although
      many rules for drug dosage have been developed, based on age, weight and surface
      area, none has been accurate and simple enough for routine use. These rules are
      described, and one for clinical use: up to 30 kg, a child's drug dose may be (wt
      x 2)% of an adult dose; over 30 kg, (wt + 30)% of an adult dose. If this
      percentage of an "adult" dose of a drug is used, not only is the BSA curve
      followed more closely than with the conventional mg kg-1 regimen, but fewer major
      errors of prescription may be expected.

PMID- 9175983
TI  - Multimodal approach to control postoperative pathophysiology and rehabilitation.
AB  - Major surgery is still associated with undesirable sequelae such as pain,
      cardiopulmonary, infective and thromboembolic complications, cerebral
      dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged
      convalescence. The key pathogenic factor in postoperative morbidity, excluding
      failures of surgical and anaesthetic technique, is the surgical stress response
      with subsequent increased demands on organ function. These changes in organ
      function are thought to be mediated by trauma-induced endocrine metabolic changes
      and activation of several biological cascade systems (cytokines, complement,
      arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To
      understand postoperative morbidity it is therefore necessary to understand the
      pathophysiological role of the various components of the surgical stress response
      and to determine if modification of such responses may improve surgical outcome.
      While no single technique or drug regimen has been shown to eliminate
      postoperative morbidity and mortality, multimodal interventions may lead to a
      major reduction in the undesirable sequelae of surgical injury with improved
      recovery and reduction in postoperative morbidity and overall costs.

PMID- 9175984
TI  - Concentration and second gas effects: can the accepted explanation be improved?
AB  - During induction with high inspired concentrations of nitrous oxide, net uptake
      of gas produces a contraction in volume and a concentrating effect. In turn, this
      results in concentration and second gas effects. Most explanations of these
      effects are based on the common "rectangle" diagram devised by Stoelting and Eger
      and contain several inconsistencies which are explored here in order to produce a
      more accurate description. It is shown that in the standard diagram gas uptake is
      incomplete, there is ambiguity over functional residual capacity (FRC),
      equilibration with blood is inadequately represented and there is no
      representation of recirculation of anaesthetic. Compensation for loss of volume
      may be by means of an increased inspired ventilation, decreased expired
      ventilation or reduction in lung volume. Numerous accounts in the literature
      (including those based on the standard diagram) focus on the former mechanism at
      constant FRC. This has produced an unbalanced picture in which it is often
      implied that extra gas is routinely drawn into the lungs to replace that taken
      up. Significant compensation by this means cannot occur, for example when a
      constant volume ventilator is used. In discussing concentration and second gas
      effects, it is necessary to give a balanced view of the alternative mechanisms of
      compensation or to revert, as above, to a simple statement of the principle of
      conservation of volume.

PMID- 9175985
TI  - Sternomental distance as predictor of difficult laryngoscopy.

PMID- 9175986
TI  - Neuromuscular block in children.

PMID- 9175987
TI  - Cutting paediatric tracheal tubes--a potential cause of morbidity.

PMID- 9175988
TI  - Lead by example.

PMID- 9175989
TI  - Diet and haemostasis: time for nutrition science to get more involved.
AB  - Abnormal haemostasis, and specifically a pre-thrombotic state characterized by
      hypercoagulability, increased platelet aggregation and impaired fibrinolysis, is
      associated with increased atheroma and thrombosis. The recent literature clearly
      indicates that diet may prevent or be used to treat some abnormal haemostatic
      states. There are reports on effects of energy intake and expenditure, alcohol
      consumption, intakes of total fat, different fatty acids, fish oil, NSP and
      vitamins on markers of coagulation, platelet function and fibrinolysis. Some of
      the confusion and controversy in this field has arisen because the wrong markers
      of haemostasis have been measured in dietary trials. Moreover, many of the
      studies have lacked good dietary control. It is suggested that more sensitive,
      functional markers of the balance between the different facets of the haemostatic
      system should be measured. It is also important to test hypotheses developed from
      known observations and to propose mechanisms of action of the various dietary
      factors, based on our improved understanding of the haemostatic system.

PMID- 9175990
TI  - Protein requirements and ageing: metabolic demand and efficiency of utilization.
AB  - The protein requirements of the elderly were investigated with [13C]leucine
      balance studies of metabolic demand, the efficiency of postprandial protein
      utilization (PPU) and the consequent apparent protein requirement. Ten elderly
      subjects aged 68-91 years (five men and five women) and ten young adult subjects
      aged 21-31 years (five men and five women) were infused with L-[1-13C]leucine for
      9 h commencing in the postabsorptive state (0-3 h), continuing during the half
      hourly feeding of low-protein meals (LP; protein 3% energy, 3-6 h), and during
      similar feeding of isoenergetic higher protein meals (HP; protein 15% energy, 6-9
      h). Leucine oxidation and balance were determined from plasma [1-13C]-alpha
      ketoisocaproate enrichment and expired 13CO2 excretion measured during the 3rd
      hour of each 3 h period. The protein intake during the HP phase was similar to
      the habitual intake estimated in the subjects from 24 h urinary N excretion.
      Metabolic demand was defined as equal to twice the body-protein equivalent of
      measured postabsorptive leucine oxidation. The efficiency of PPU was calculated
      from the increased leucine oxidation observed during feeding, and the apparent
      protein requirement was defined as metabolic demand/PPU and calculated in
      relation to both body weight (BW) and fat-free mass (FFM) determined by
      densitometry or bioimpedance. Metabolic demand in the young adults was 0.83 g
      protein/kg per d; in both elderly groups it was 36% lower when expressed per kg
      BW and 30% lower when expressed per kg FFM. The apparent protein requirement
      calculated from metabolic demand and PPU was 0.99 g protein/kg per d in the young
      adults and this was also lower in the elderly, although this was only significant
      in the men (0.66 g per kg BW, P = 0.013; 0.79 g per kg FFM, P = 0.02). The
      results show that in this group of healthy elderly adults protein requirements as
      assessed from leucine balance studies were either similar to or less than those
      of younger adults.

PMID- 9175991
TI  - Low-sodium diet in pregnancy: effects on blood pressure and maternal nutritional
      status.
AB  - In ninety-four Dutch nulliparous women the effects of a low-Na diet in pregnancy
      on blood pressure, energy and nutrient intake, Ca metabolism, Zn and Mg status
      and body composition were studied longitudinally. The women were randomly divided
      into an intervention group (n 41), which used a low-Na diet (mean urinary Na
      excretion 61 mmol/24 h) from week 14 of pregnancy until delivery and a control
      group (n 53; mean urinary Na excretion 142 mmol/24 h). No effect of the diet on
      blood pressure was observed. The use of a low-Na diet resulted in significantly
      reduced intakes of energy, protein, carbohydrates, fat, Ca, Zn, Mg, Fe and
      cholesterol. However, the women on the low-Na diet appeared to be able to adapt
      quite well to the reduced intake since Ca, Zn and Mg homeostasis was maintained.
      In the case of Ca and Mg this was probably due to the observed reduced urinary
      excretions of these nutrients. Non-significant reductions in weight gain (1.5 kg)
      and fat-mass gain (0.9 kg) over pregnancy were found in the women on the low-Na
      diet. No significant effects of the diet on birth weight or placental weight were
      observed.

PMID- 9175992
TI  - Calcium excretion, apparent calcium absorption and calcium balance in young and
      elderly subjects: influence of protein intake.
AB  - The present study was conducted to investigate the effect of dietary protein on
      urinary Ca excretion, apparent Ca absorption and Ca balance in young and elderly
      subjects. Young adults (n 29) and elderly persons (n 26) consumed diets
      containing 12% (diet A) and 21% (diet B) of total energy as protein for 3 weeks
      according to a randomized crossover design. Results showed no differences between
      the two age groups with respect to the interaction between protein intake and Ca
      excretion (both in urine and in faeces), apparent Ca absorption and Ca balance.
      Therefore analyses were done for both age groups separately and also for the
      whole group. In elderly persons and in the whole group the Ca excretion in faeces
      (as a percentage of Ca intake) was lower during the higher protein intake
      (elderly: diet A, 106 (SEM 7)%; diet B, 86 (SEM 7)%; P = 0.018; whole group: diet
      A, 99 (SEM 4)%; diet B, 84 (SEM 4)%; P = 0.003). In young adults faecal Ca
      excretion tended to be lower when they consumed diet B (diet A: 94 (SEM 5)%; diet
      B: 83 (SEM 6)%; P = 0.093). Relative urinary Ca excretion was greater during the
      higher protein intake in young adults and in the whole group while relative
      urinary Ca excretion was not different in the elderly (diet A: 15 (SEM 1)%, 14
      (SEM 1)%, 15 (SEM 1)%; diet B: 16 (SEM 1)%, 16 (SEM 1)%, 17 (SEM 2)% for the
      whole group, the young and elderly subjects respectively, P = 0.019; P = 0.016; P
      = 0.243). The resulting Ca balance was not influenced by the amount of protein in
      the diet in young adults. Values for the elderly and for the whole group showed
      that the Ca balance during diet A was significantly more negative compared with
      Ca balance during diet B, despite the higher urinary Ca excretion during diet B.
      It can be concluded that increasing the protein intake from 12 to 21% of total
      energy intake had no negative effect on Ca balance.

PMID- 9175993
TI  - Comparison of growth performance and nutrient retention of weaner pigs given
      diets based on casein, free amino acids or conventional proteins.
AB  - In two experiments the potential value of diets based on casein or free amino
      acids (FAA) for amino acid utilization experiments were examined. In Expt 1 the
      optimum dietary electrolyte balance (dEB) for a casein-based diet was estimated
      by supplemention with 10 or 20 g NaHCO3/kg, to produce diets containing 64, 183
      or 302 mmol/kg. In addition, piglet growth performance and efficiency of nutrient
      deposition of piglets given the casein diets were compared with two multiple
      protein source diets; Supercreep, a commercial multiple protein source diet or
      CFS (casein-fish-soyabean-sugar) or a FAA-based diet. Expt 2 was designed to
      compare piglet response to FAA diet stored at -15 degrees with twice daily
      feeding, with FAA diet stored at ambient temperature (13-30 degrees) and offered
      ad libitum. A CFS diet was used as a positive control and the experiment was
      conducted over the 10-20 kg growth phase. Expt 1 used forty-eight piglets weaned
      at 20-22 d of age and allocated to one of six treatments formulated to contain at
      least 0.84 g lysine/MJ digestible energy in a randomized block design. Piglets
      given the CFS and Supercreep diets produced superior growth rates (518, 491 g/d)
      to those given a FAA diet (353 g/d) or casein diet containing 0, 10 or 20 g
      NaHCO3/kg respectively (365, 417, 390 g/d) between 5 and 20 kg live weight.
      Piglets given the casein and FAA diets had higher amino acid digestibilities than
      those given the Supercreep and CFS diets. The increase in the dEB of the casein
      diet from 64 to 183 mmol/kg improved piglet growth performance between 5 and 20
      kg by 14%. All piglets given casein diets had similar ileal and faecal
      digestibilities, empty-body compositions, nutrient deposition rates and retention
      ratios. The results of Expt 2 showed that there was no beneficial effect on
      piglet performance of storing the FAA diet at -15 degrees and feeding twice
      daily. Based on the results of these two experiments, neither the casein (0, 10,
      20 g NaHCO3/kg) nor FAA diets were suitable for estimating amino acid utilization
      by the piglet. There remain unidentified factors which limit the growth
      performance of piglets given the casein and FAA diets.

PMID- 9175994
TI  - The energy value of short-chain fatty acids infused into the caecum of pigs.
AB  - The present work was undertaken to study the energy value of a mixture of acetic,
      propionic and butyric acids (0.682:0.226:0.092) infused intracaecally in growing
      pigs. A basal diet low in fibre (42 g NSP/kg DM) was given at below the
      requirement for maximum weight gain. In six 2-week periods, N and energy balance
      measurements in eight growing pigs were carried out with and without infusion of
      short-chain fatty acids (SCFA). Heat production was measured using open-circuit
      chambers and the concentration of SCFA in faeces was determined. Less than 1% of
      the infused SCFA was excreted in faeces illustrating the capacity of the hind-gut
      to absorb and metabolize SCFA. Infusion of SCFA did not affect the digestibility
      of nutrients and energy. However, N retention increased demonstrating that SCFA
      are an energy source for protein gain when pigs are fed at below the requirement
      of energy. Increased CH4 production together with an increased excretion of
      branched-chain fatty acids in faeces suggested that there was a higher microbial
      activity in the hind-gut during infusion. The partial utilization of the infused
      energy in SCFA was 0.821. A small proportion of the infused energy in SCFA was
      retained in protein (0.099) and a considerable amount was retained as fat
      (0.722).

PMID- 9175995
TI  - The degradability characteristics of fifty-four roughages and roughage neutral
      detergent fibres as described by in vitro gas production and their relationship
      to voluntary feed intake.
AB  - Fifty-four roughages of known voluntary dry-matter intakes (DMI; range 7.8-35.2
      g/kg live weight per d) were examined in vitro in a gas production test. Samples
      (200 mg) of roughage and roughage neutral-detergent fibre (NDF) respectively were
      incubated in a mixed suspension of rumen contents for 96 h and the gas volumes
      recorded after 4, 6, 8, 12, 24, 30, 36, 48, 54, 60 and 96 h. The kinetics of gas
      production were derived from the volume recordings described by the exponential
      equation Y = A + B(l-e-ct) where A is the intercept and ideally reflects the
      fermentation of the soluble and readily available fraction of the feed, B
      describes the fermentation of the insoluble (but with time fermentable) fraction
      and c the fractional rate at which B is fermented per h; A + B describes total
      fermentation. In vitro true dry matter (TD) and NDF degradabilities (NDF-D) after
      24 h incubation were also determined. Of the variation in DMI, 75% was accounted
      for by the in vitro gas production parameters A, B and c in stepwise multiple
      regressions; 82% of the variation in DMI was explained by the parameters (ANDF +
      BNDF) and cNDF as obtained from the incubation of roughage NDF. The rate
      constants (c) were less important than parameters related to the extent of gas
      production, accounting for only 6.5 (whole roughage) and 4.1% (NDF) of the
      variation in DMI. There was no statistical advantage in the use of the
      exponential model describing extent and rate of fermentation over some of the
      simple gas volume measurements: 75% of the variation in DMI was accounted for by
      in vitro gas production of whole roughage after 8 h of incubation. On average gas
      production from NDF measured from 24-96 h accounted for 81% of the variation in
      DMI. A combination of gas volume measurements after a short period of incubation
      (4-8 h) with a concomitant determination of NDF-D after many hours (> or = 24 h)
      can render NDF preparations and long incubation times redundant. A method is
      suggested to obtain two results for DMI prediction in one single incubation. Of
      the variation in DMI 80% was accounted for by the incubation of 500 mg whole
      roughage when incubation was terminated after 24 h and the residual undegraded
      substrate quantified.

PMID- 9175996
TI  - Net flux of nutrients across splanchnic tissues in wethers consuming grasses of
      different sources and physical forms ad libitum.
AB  - Crossbred sheep (n 16, 8.5 months of age and 33 (SE 0.9) kg) were used in a 21 d
      experiment (2 x 2 factorial) to determine effects on net flux of nutrients across
      the portal-drained viscera (PDV) and liver of ad libitum consumption of
      bermudagrass (Cynodon dactylon; B) v. ryegrass (Lolium multiflorum)-wheat
      (Triticum aestivum; RW) hay, coarsely chopped (CC) or finely ground and pelleted
      (GP). Crude protein concentrations were 86, 81, 113 and 119 g/kg and neutral
      detergent fibre concentrations were 710, 688, 654 and 672 g/kg (dry matter basis)
      for B-CC, B-GP, RW-CC and RW-GP respectively. Digestible energy intake (6.0, 9.6,
      10.2 and 13.8 MJ/d) differed (P < 0.01) with grass source and form, and
      digestible N intake values were 4.4, 7.0, 8.4 and 14.1 (SEM 0.82) g/d for B-CC, B
      GP, RW-CC and RW-GP diets respectively. Consumption of O2 by the PDV (118, 165,
      144 and 155 mmol/h) and splanchnic bed (196, 273, 247 and 266 mmol/h for B-CC, B
      GP, RW-CC and RW-GP respectively) was greater (P = 0.07) for GP than for CC. The
      ratio splanchnic heat energy production: digestible energy intake was greater (P
      = 0.06) for B than for RW (0.374, 0.300, 0.278 and 0.219 for B-CC, B-GP, RW-CC
      and RW-GP respectively). alpha-Amino-N release by the PDV (P < 0.01; 11.6, 12.8,
      23.0 and 18.7 mmol/h) and uptake by the liver (P = 0.07; 15.2, 6.1, 17.0 and 19.3
      mmol/h for B-CC, B-GP, RW-CC and RW-GP respectively) were greater for RW than for
      B. Release of NH3-N by the PDV was greater (P = 0.02) for CC than for GP (12.5,
      6.2, 15.7 and 8.9 mmol/h), and hepatic urea-N release differed between grass
      sources (P = 0.03) and physical forms (P = 0.07; 22.6, 12.7, 31.4 and 24.8 mmol/h
      for B-CC, B-GP, RW-CC and RW-GP respectively). In conclusion, decrease in forage
      particle size elicited by grinding and pelleting did not affect the difference
      between grass sources in splanchnic tissue heat energy production relative to
      digestible energy intake.

PMID- 9175997
TI  - Uptake and metabolism of propionate in the liver isolated from sheep treated with
      glucagon.
AB  - The uptake and metabolism of propionate in the isolated perfused caudal lobe of
      the liver and in isolated hepatocytes were examined following treatment of sheep
      with glucagon or saline. Glucagon or sterile saline was infused at 9.8
      micrograms/min for 3 h into the jugular vein and then the caudal lobe of the
      liver was removed surgically under anaesthesia. The caudal lobe was used either
      to prepare hepatocytes or in a non-recirculating perfusion experiment. Uptake and
      metabolism of propionate were studied using [2-14C]propionate. In studies using
      the non-recirculation perfusion of the caudal lobe of the sheep liver it was
      shown that the treatment of sheep with glucagon resulted in an increased rate of
      gluconeogenesis from propionate and in an increased net uptake of propionate by
      the caudal lobe. The uptake of propionate into the hepatocytes was saturable,
      concentrative and exhibited a K(m) for propionate of 0.24 (SE 0.07) mM and a
      maximal rate of uptake (Vmax) of 6.7 (SE 0.6) nmol/mg dry cells per min and was
      unaffected by glucagon treatment of sheep. After incubation of cells in medium
      containing 0.5 mM-[2-14C]propionate for 10 min, the rate of gluconeogenesis from
      propionate was 22% higher in the hepatocytes isolated from glucagon-treated
      sheep. Concentrations in the medium of 1.35 mM butyrate and 1 mM-caproate
      inhibited propionate uptake by about 50% and abolished the glucagon-induced
      stimulation of gluconeogenesis from propionate. The results are consistent with a
      regulatory role for glucagon in the gluconeogenesis from propionate in the sheep
      liver.

PMID- 9175998
TI  - Modulation of age-related changes in immune functions of protein-deficient
      senescence-accelerated mice by dietary nucleoside-nucleotide mixture
      supplementation.
AB  - In the present study we examined the immune-enhancing effect of a nucleoside
      nucleotide mixture on the non-specific T-cell immune functions of senescence
      accelerated mice (SAM) fed on a low-protein diet. The immune functions studied
      were in vitro thymic and splenic cell lymphoproliferative responses to
      phytohaemagglutinin, lipopolysaccharide and concanavalin A and their production
      of interleukin-2 (IL-2) and interferon-gamma (INF-gamma) in response to mitogen
      stimulation. SAMP8 mice aged 3 and 6 months were used. In each age group, mice
      were fed on diets containing either 50 g casein/kg, 50 g casein/kg supplemented
      with 5 g nucleoside-nucleotide mixture/kg or 200 g casein/kg for 3 weeks. The
      supplemented 3- and 6-month-old mice had higher (P < 0.05) thymic and splenic
      cell counts compared with the low-protein group. In both age groups of mice,
      concanavalin A induced higher (P < 0.05) total thymic and splenic
      lymphoproliferative responses for the nucleoside-nucleotide mixture-supplemented
      group compared with the 50 g casein/kg dietary groups. Thymic and splenic
      production of IL-2 was higher for the 3-month-old mice in both the supplemented
      and the 200 g casein/kg dietary groups. INF-gamma production in the supplemented
      3-month-old group and the 6-month-old 200 g casein/kg dietary group was higher (P
      < 0.05) compared with the other groups. Overall the supplemented 3-month-old mice
      exhibited both higher lymphoproliferative responses and production of cytokines
      compared with the supplemented 6-month-old mice. The results indicate that early
      nucleoside-nucleotide mixture supplementation may enhance the immune response in
      protein-deprived SAMP8 mice.

PMID- 9175999
TI  - Effects of variations in the proportions of saturated, monounsaturated and
      polyunsaturated fatty acids in the rat diet on spleen lymphocyte functions.
AB  - To obtain further information about the immunomodulatory effects of specific
      dietary fatty acids, weanling male rats were fed for 6 weeks on high-fat (178
      g/kg) diets which differed according to the principal fatty acids present. The
      nine diets used differed in their contents of palmitic, oleic, linoleic and alpha
      linolenic acids; as a result the total polyunsaturated fatty acid (PUFA) content
      and the PUFA:saturated fatty acid ratio varied (from 17.8 to 58.5 g/100 g fatty
      acids and from 0.28 to 5.56 respectively). The n-6 PUFA:n-3 PUFA ratio was kept
      constant in all diets at approximately 7.0. The fatty acid composition of the
      serum and of spleen lymphocytes were significantly influenced by that of the diet
      fed. The ex vivo proliferation of spleen lymphocytes decreased as the level of
      oleic acid in the diet increased. Spleen natural killer cell activity decreased
      as the oleic acid content of the diet increased and increased as the palmitic
      acid content of the diet increased. The extent of the effects of these fatty
      acids on lymphocyte functions was modified by the nature of the background fatty
      acid composition of the diet.

PMID- 9176000
TI  - Craniofrontonasal dysplasia.
AB  - A series of 10 patients with craniofrontonasal dysplasia presenting to the Oxford
      Craniofacial Unit since 1983 is presented. In addition to the well-described
      combination of coronal synostosis and frontonasal dysplasia, 9 patients had very
      characteristic dry, curly or frizzy hair. All the patients were female.
      Recognition of the syndrome is important for genetic counselling, although the
      precise mode of genetic transmission is unclear with females predominating and
      males being less severely affected. Surgical correction was in two stages: early
      frontal advancement followed by correction of hypertelorism when the child became
      aware of the deformity. Four patients had their craniosynostosis treated in the
      Oxford Craniofacial Unit. Three patients had previously had frontal remodelling
      elsewhere. Nine patients had surgery for hypertelorism. The preferred technique
      for hypertelorism correction was facial bipartition. Following hypertelorism
      correction, the excess skin was allowed to redrape and subsequently dealt with by
      medial canthoplasties, thus avoiding a midline scar. Careful attention to the
      primary frontal advancement procedure is important to avoid complications
      following difficult dissection of the frontal bone flap at the time of
      hypertelorism correction.

PMID- 9176001
TI  - Forearm free skin flap transplantation: a report of 56 cases. 1981.

PMID- 9176002
TI  - Free arterialised venous forearm flaps for intraoral reconstruction.
AB  - In 29 patients, the intraoral defect after excision of an oral squamous cell
      carcinoma was repaired with an arterialised venous forearm flap. In all cases, a
      flap of skin and fat with a superficial vein passing through it was raised from
      the flexor surface of the right forearm. After the flap had been sutured into the
      intraoral defect, the original distal end of the vein was anastomosed to an
      artery and the original proximal end to a vein. Fifteen (52%) of the flaps
      survived completely, six (21%) had superficial epithelial loss or some marginal
      necrosis and eight (27%) became completely necrotic. Areas of partial loss
      developed slowly and formed stable granulation tissue. The flap donor sites were
      either closed primarily (n = 20) or were covered with a split thickness skin
      graft (n = 9). There were no functional problems of the donor forearms. These
      results contrast with the high success rates achieved with orthodox free radial
      forearm flaps. Further research into venous flaps is essential.

PMID- 9176003
TI  - Colour Doppler flow imaging of postauricular arteries and veins.
AB  - The posterior auricular vessels of both ears in 15 normal human adults were
      examined using a colour Doppler flow imager to investigate whether the imager
      might be helpful in preoperative assessment of the blood supply of the
      retroauricular skin. Thirty posterior auricular arteries and 23 posterior
      auricular veins were identified. A reversed arterial flow was observed in 15 out
      of 30 ears and a reversed venous flow was observed in 4 out of 30 ears after the
      blood flow of the vessel was stopped by applying pressure manually at the level
      of the mastoid process. The assessment of the size and location of the posterior
      auricular vessels with a colour Doppler flow imager is valuable in the planning
      of flaps based on these vessels. Furthermore, the observation of the reversed
      flow confirms the possibility of safe elevation of a posterior auricular flap
      based on the tributaries of the superficial temporal vessels.

PMID- 9176004
TI  - Long-term results of weight-bearing foot reconstruction with non-innervated and
      reinnervated free flaps.
AB  - Twenty one patients underwent reconstruction of the weight-bearing portion of the
      foot with 22 free flap transfers: 12 free flaps were skin-grafted muscle flaps
      and 10 were fasciocutaneous flaps. Twelve flaps were reinnervated by nerve
      coaptation (n = 10) or an 'onlay' nerve graft (n = 2). Follow-up ranged from 1.5
      to 7 years (mean 38.5 months). Five flaps (23%) developed full thickness ulcers
      that required surgical treatment. All ulcers occurred in patients who had an
      underlying neuropathy. Most complications occurred early in the series. No
      significant difference was found in the incidence of complications and functional
      outcome between fasciocutaneous and skin-grafted muscle flaps. There was no
      significant difference between reinnervated and non-innervated flaps. Both
      fasciocutaneous and skin-grafted muscle flaps, whether reinnervated or non
      innervated, can be successfully used for weight-bearing foot reconstruction.
      Neither type of flap should be considered permanent in the presence of peripheral
      neuropathy. Appropriate selection of patients, extensive education about foot
      care and frequent follow-up visits are essential to maintain a healthy, intact
      flap and reconstructed foot.

PMID- 9176005
TI  - Prevention of painful neuromas by epineural ligatures, flaps and grafts.
AB  - Neuroma formation at the proximal end of a divided nerve is a common problem in
      peripheral nerve surgery. Forty-eight nerve endings in 23 patients with traumatic
      or post-elective surgery amputation stumps were capped with either an epineural
      ligature, epineural flaps or an epineural graft. Each technique was used on 16
      nerve endings. After at least 6 months follow-up, pain at the nerve endings was
      assessed by tapping the treatment sites and asking the patients to score their
      pain on a visual analogue scale (VAS) from 0 to 10. The mean VAS scores were 5.18
      for epineural ligatures, 4.25 for epineural flaps and 2.06 for epineural grafts.
      Epineural grafts were significantly more effective in preventing neuroma pain
      (ANOVA: F = 11.4, P < 0.05).

PMID- 9176006
TI  - Growth inhibition of cultured fibroblasts by extracts from human dermis.
AB  - In incised wounds and deep partial thickness burns the resident fibroblasts in
      the dermis remain inactive. The fibroblasts responsible for repair at the dermal
      level come from the subdermal layer. The hypothesis is that the inactivity of the
      dermal fibroblasts is due to an inhibitory substance in the dermis. To test this
      hypothesis extracts were made of normal dermis and of mature scar tissue and
      these extracts were applied to fibroblasts growing in monolayer culture. Both
      extracts and cells were obtained from human tissue. It was shown that extracts,
      particularly the extract made with citric acid/citrate buffer, pH 3.5, caused
      inhibition of fibroblast growth. Present evidence suggests that the active
      principle may be a proteoglycan.

PMID- 9176007
TI  - The use of negative pressure to promote the healing of tissue defects: a clinical
      trial using the vacuum sealing technique.
AB  - A prospective clinical trial from January 1994 to February 1996 evaluated the
      efficacy of a vacuum sealing technique in dealing with sacral pressure ulcers,
      acute traumatic soft tissue defects and infected soft tissue defects following
      rigid stabilization of lower extremity fractures in 45 patients. Polyvinyl foam
      under negative pressure generates an area of high contact forces at the
      wound/foam interface. This situation appears to facilitate granulation tissue
      production while maintaining a relatively clean wound bed. In 84% (38/45) of the
      patients the use of the vacuum sealing technique following irrigation and
      debridement decreased the dimensions of the initial wound, thus facilitating
      healing time and the eradication of any pre-existing infection. Wound closure by
      granulation, secondary closure, or split thickness skin grafting was achieved in
      35 wounds. The vacuum sealing technique is an effective option in the management
      of infected wounds.

PMID- 9176008
TI  - Measuring outcomes in plastic surgery. Kay-Kilner Prize Essay 1996.

PMID- 9176009
TI  - Urethral advancement and glanuloplasty (UGPI): a modification of the MAGPI
      procedure for distal hypospadias.
AB  - A modification of the meatal advancement and glanuloplasty technique (MAGPI), the
      urethral advancement and glanuloplasty (UGPI), is described. Forty-seven
      patients, who had this operation from 1985 to 1994, have been reviewed. The
      overall complication rate was low with a 2.1% fistula rate and a 6.4% incidence
      of meatal retraction. Only one patient required secondary surgery.

PMID- 9176010
TI  - The surgical management of incomplete testicular feminization syndrome in three
      sisters.
AB  - Three sisters with incomplete testicular feminization syndrome are presented.
      Most of the patients with this syndrome are females and surgery is an important
      part of their multidisciplinary treatment. Two of the sisters had gonadectomies,
      herniorrhaphies, vaginoplasty with neurovascular pudendal thigh flaps, reduction
      clitoroplasty and labia minora reconstruction. The third sister had sufficient
      vaginal depth and had release of an introitus skin web, clitoroplasty and labia
      minora reconstruction. All patients had a good result. The reconstructed vaginas
      are stable and sensate.

PMID- 9176011
TI  - Early feeding after cleft repair.

PMID- 9176012
TI  - Tissue expansion of a forehead flap for nasal reconstruction.

PMID- 9176013
TI  - The extended role of the surgical glove.

PMID- 9176014
TI  - Endoscopically assisted latissimus dorsi harvest and prosthetic placement.

PMID- 9176015
TI  - The hepatorenal syndrome.
AB  - 1. The hepatorenal syndrome is the development of renal failure in patients with
      severe liver disease in the absence of any identifiable renal pathology. 2.
      Decreased glomerular filtration is caused by a reduction in both renal blood flow
      and the renal filtration fraction. These changes arise as a consequence of a fall
      in mean arterial pressure due to systemic vasodilatation, activation of the
      sympathetic nervous system causing renal vasoconstriction, and increased
      synthesis of several vasoactive mediators, which together modulate both renal
      blood flow and the glomerular capillary ultrafiltration coefficient, and thence
      filtration fraction. 3. Patients with liver disease developing renal failure
      should have hypovolaemia excluded by volume challenge, and all nephrotoxic drugs
      including diuretics should be stopped. Broad-spectrum antibiotics should be given
      for subclinical infection, which may be a treatable precipitant of renal failure
      in cirrhosis. Renal perfusion should be optimized by ensuring that the blood
      pressure and systemic haemodynamics are adequate, and that if renal venous
      pressure is elevated, due to tense ascites, it is alleviated. 4. The prognosis of
      hepatorenal syndrome is poor with a > 90% mortality. However, patients can and do
      recover from the hepatorenal syndrome, but only if there is a significant
      improvement of their liver function, or if they undergo liver transplantation.

PMID- 9176016
TI  - Signalling pathways involved in the mitogenic effects of cAMP.
AB  - 1. Elevation of intracellular cyclic AMP (cAMP) is a potent mitogenic signal for
      a number of cell types, including Swiss 3T3 cells, thyroid epithelial cells and
      the somatotroph cells of the anterior pituitary. 2. Activation of the mitogen
      activated protein kinase (MAPK) cascade has been shown to underlie the mitogenic
      effects of many growth factors. However, the precise relationship between the
      mitogenic effects of cAMP and the MAPK cascade is not fully defined. 3. In Swiss
      3T3 cells, elevation of cAMP did not stimulate kinases at all three levels of the
      MAPK cascade. Additionally, blockade of the MAPK pathway failed to inhibit cAMP
      stimulated DNA synthesis. 4. Mitogenic combinations of cAMP strongly stimulated
      the phosphorylation and activation of the serine/threonine kinase p70 S6 kinase,
      p70S6K, an effect that was inhibited by rapamycin. This agent markedly inhibited
      cAMP-stimulated DNA synthesis, suggesting a critical role for p70S6K in cAMP
      mitogenic signalling. 5. Thus, multiple parallel but distinct signalling pathways
      may be involved in the action of mitogens. This redundancy has important
      implications for the pathogenesis and treatment of conditions characterized by
      inappropriate activation of growth factor signalling pathways.

PMID- 9176017
TI  - Serum levels of vascular endothelial growth factor in patients with acute
      myocardial infarction undergoing reperfusion therapy.
AB  - 1. Vascular endothelial growth factor, a potent angiogenic mitogen, is known to
      be induced in response to ischaemia as well as being secreted from tumour cells.
      However, the precise mechanism of vascular endothelial growth factor release in
      acute myocardial infarction and the effects of coronary reperfusion on the
      circulating levels of vascular endothelial growth factor are still unknown. 2.
      Nineteen patients with acute myocardial infarction who underwent early
      reperfusion therapy were studied. Serum levels of vascular endothelial growth
      factor before reperfusion were markedly increased as compared with those in 19
      healthy control subjects [252.4 +/- 158.1 pg/ml (mean +/- SD) compared with
      undetectable]. After reperfusion, the serum vascular endothelial growth factor
      levels rapidly returned almost completely to the normal control range. 4. These
      data strongly suggest that the serum level of vascular endothelial growth factor
      is one of the most sensitive indicators of myocardial ischaemia.

PMID- 9176018
TI  - Tissue expression of components of the renin-angiotensin system in experimental
      post-infarction heart failure in rats: effects of heart failure and angiotensin
      converting enzyme inhibitor treatment.
AB  - 1. It has been suggested that local tissue renin-angiotensin systems may be
      activated in heart failure and that effects on such systems may, at least
      partially, explain the beneficial effects of angiotensin-converting enzyme (ACE)
      inhibitors in this syndrome. To investigate these hypotheses, we examined
      expression of renin-angiotensin system components in several tissues in a rodent
      model of post-myocardial infarction (MI) heart failure, and analysed whether such
      expression is modified by ACE inhibitor treatment. 2. Four groups of rats (n = 8 
      12 per group) were studied 30 days after surgery: (A) sham-operated rats with no
      treatment, (B) rats with post-MI heart failure induced by ligation of the left
      coronary artery, (C) sham-operated rats treated with the ACE inhibitor
      perindopril (1.5 mg day-1 kg-1), and (D) rats as per B, but treated with
      perindopril. Expression of renin, angiotensinogen, ACE and angiotensin subtype 1
      receptor was assessed by quantification of their respective mRNAs by Northern
      blotting. 3. Renal renin mRNA increased 2-fold in animals with MI (group B)
      compared with controls (group A) (P < 0.05) and between 50 and 100-fold after ACE
      inhibitor treatment (P < 0.001). No change in renin gene expression was found in
      any extra-renal site either following MI or after ACE inhibitor treatment.
      Hepatic angiotensinogen mRNA level was similar in all groups, but kidney
      angiotensinogen mRNA level was increased 1.6-fold (P < 0.01) in the groups
      receiving perindopril. ACE mRNA level in the lung was not affected by ACE
      inhibitor treatment but decreased by 50% following MI (groups B and D, P < 0.01).
      This was associated with a similar (50%, P < 0.01) fall in lung ACE activity and
      was correlated with the severity of heart failure. Angiotensin subtype 1 receptor
      mRNA level was not affected in any tissue by either MI or ACE inhibitor
      treatment. 4. We did not find a systematic activation of tissue renin-angiotensin
      systems, as assessed by steady-state mRNA levels of key components of the system
      in experimental post-MI heart failure, or a major effect of ACE inhibitor
      treatment on expression of these components. However, we observed tissue-specific
      changes in expression of selected components of the renin-angiotensin system in
      the kidney and the lung in post-MI heart failure and after ACE inhibitor
      treatment, which may be of relevance to the pathophysiology of the syndrome and
      the effects of ACE inhibition.

PMID- 9176019
TI  - Adrenomedullin: a hypotensive hormone in man.
AB  - 1. Adrenomedullin, a recently discovered 52-amino-acid peptide hormone,
      circulates in plasma at low picomolar levels in man. Animal studies and studies
      in vitro indicate that it has diverse biological actions, including
      vasodilatation, natriuresis and diuresis, and positive inotropism as well as anti
      proliferative effects. We investigated the bioactivity of two doses of
      adrenomedullin in healthy human subjects. 2. Human adrenomedullin was given
      intravenously to eight male subjects at 2 and 8 ng min-1 kg-1, and haemodynamic,
      hormonal, renal and biochemical responses were recorded in a placebo (vehicle)
      controlled, randomized study. 3. Compared with vehicle, adrenomedullin reduced
      mean arterial pressure (P = 0.05 for duration of infusion, mean difference at end
      of infusion 7.7 mmHg), systolic arterial pressure (P = 0.04 for duration of
      infusion, mean difference at end of infusion 10.7 mmHg) and at the lower dose
      reduced diastolic arterial pressure (P = 0.05 for lower dose, mean difference at
      end of infusion 6.3 mmHg) in the absence of compensatory responses in sympathetic
      activity or renin release. Urine volume and electrolyte excretion were
      unaffected. 4. The threshold for biological activity of adrenomedullin in man is
      lower, for arterial pressure than for renal or hormonal responses, and is evident
      at plasma concentrations seen in disorders of the circulation. Adrenomedullin may
      be an important hormone under pathophysiological circumstances.

PMID- 9176020
TI  - The effects of low-density lipoprotein and high-density lipoprotein on blood
      viscosity correlate with their association with risk of atherosclerosis in
      humans.
AB  - 1. Increased blood or plasma viscosity has been observed in almost all conditions
      associated with accelerated atherosclerosis. Cognizant of the enlarging body of
      evidence implicating increased viscosity in atherogenesis, we hypothesize that
      the effects of low-density lipoprotein and high-density lipoprotein on blood
      viscosity correlate with their association with risk of atherosclerosis. 2. Blood
      viscometry was performed on samples from 28 healthy, non-fasting adult volunteers
      using a capillary viscometer. Data were correlated with haematocrit, fibrinogen,
      serum viscosity, total cholesterol, high-density lipoprotein-cholesterol,
      triglycerides and calculated low-density lipoprotein-cholesterol. 3. Low-density
      lipoprotein-cholesterol was more strongly correlated with blood viscosity than
      was total cholesterol (r = 0.4149, P = 0.0281, compared with r = 0.2790, P =
      0.1505). High-density lipoprotein-cholesterol levels were inversely associated
      with blood viscosity (r = -0.4018, P = 0.0341). 4. To confirm these effects,
      viscometry was performed on erythrocytes, suspended in saline, which had been
      incubated in plasma of various low-density lipoprotein/high-density lipoprotein
      ratios. Viscosity correlated directly with low-density lipoprotein/high-density
      lipoprotein ratio (n = 23, r = 0.8561, P < 0.01). 5. Low-density lipoprotein
      receptor occupancy data suggests that these effects on viscosity are mediated by
      erythrocyte aggregation. 6. These results demonstrate that the effects of low
      density lipoprotein and high-density lipoprotein on blood viscosity in healthy
      subjects correlate with their association with risk of atherosclerosis. These
      effects on viscosity may play a role in atherogenesis by modulating the dwell or
      residence time of atherogenic particles in the vicinity of the endothelium.

PMID- 9176021
TI  - Effects of hydroxyurea administration on the body weight, body composition and
      exercise performance of patients with sickle-cell anaemia.
AB  - 1. As an ancillary study carried out during the recently completed Multicenter
      Study of Hydroxyurea, we examined the effect of hydroxyurea on the body weight,
      body composition and exercise capacity of adult patients with sickle-cell
      anaemia. 2. The subjects received either hydroxyurea (six males and four females)
      or placebo (eight males and six females). Data for each subject were generated
      during four separate 24 h admissions to the General Clinical Research Center.
      These admissions occurred at baseline and then at 6, 12 and 18 months after the
      start of study drug (hydroxyurea or placebo) administration. During each
      admission, body composition was measured by using a dual X-ray absorptiometer,
      and exercise testing was performed by cycle ergometry. Anaerobic performance was
      assessed according to a 'Wingate' protocol (20 s at maximal intensity against a
      cycling resistance of 7.5% body weight). Aerobic performance was examined using a
      steady state submaximal exercise protocol (10 min cycling time). 3. At baseline,
      no significant difference in any parameter was found between the hydroxyurea- and
      placebo-treated groups. At 18 months, the hydroxyurea-treated subjects exhibited
      an average weight gain of 3.16 kg. The mean weight gain in the placebo-treated
      subjects was 1.82 kg. Body composition analysis showed that the additional weight
      in both groups involved both lean and fat body mass components. In anaerobic
      performance, the subjects given hydroxyurea showed an increase in peak muscle
      power of 104.9 W. The placebo group also showed an increase, but theirs was a
      more modest gain of 57.7 W. The most marked improvement in anaerobic performance
      was observed in the hydroxyurea-treated men (P < 0.05). In aerobic performance,
      the hydroxyurea-treated subjects exhibited a decrease in peak heart rate response
      to a standardized workload of 15.2 beats/min, as compared with a decrease of only
      4.3 beats/min in the placebo-treated patients. 4. Taken together, the overall
      weight gain, combined with increases in both anaerobic muscular performance and
      aerobic cardiovascular efficiency, provides objective data to support the
      subjective impression that hydroxyurea administration produces an improvement in
      the physical capacity of patients with sickle-cell anaemia.

PMID- 9176022
TI  - Female sex hormones do not influence arterial wall properties during the normal
      menstrual cycle.
AB  - 1. In previous studies, the elastic properties of the common carotid artery were
      found to differ between men and women. In these studies, however, the phase of
      the menstrual cycle was not taken into consideration. It was the aim of the
      present study to investigate the effect of changing ovarian hormone levels during
      the normal menstrual cycle on the arterial wall properties of female large
      arteries. 2. We investigated the elastic right common carotid artery and the
      muscular right common femoral artery of normotensive young (18-35 years) female
      subjects (n = 12). The arterial distensibility and cross-sectional compliance
      coefficients were determined by the use of a specially designed ultrasonic wall
      tracking device and measurements of automatic brachial artery cuff blood
      pressure. The phase of the menstrual cycle was assessed by ultrasonographic
      evaluation and measurement of 17 beta-oestradiol and progesterone blood plasma
      levels. 3. The distensibility coefficient and the cross-sectional compliance
      coefficient of both the common carotid and the common femoral artery did not
      change significantly during the normal menstrual cycle despite evidently changing
      ovarian hormone levels. 4. We conclude that the menstrual cycle does not
      influence the arterial wall properties of either the elastic common carotid
      artery or the muscular common femoral artery.

PMID- 9176023
TI  - Microdialysis of human breast tissue during the menstrual cycle.
AB  - 1. Previously it has been impossible to perform studies of human breast tissue in
      vivo. In this study, we investigated whether the microdialysis technique is
      applicable in human breast tissue and whether the concentrations of amino acids,
      lactate and pyruvate change during the menstrual cycle. 2. Microdialysis was
      performed twice during the menstrual cycle in eight healthy women, in the breast
      and subcutaneous fat. Amino acids, lactate and pyruvate were analysed by HPLC. 3.
      None of the women showed any complications, such as bleeding or infection, after
      the experiments. The concentrations of aspartic acid, asparagine, serine,
      glycine, threonine, tyrosine and ornithine were decreased in the breast late in
      the menstrual cycle. In the subcutaneous fat, the concentration of glycine
      decreased late in the cycle. 4. This study has shown that microdialysis is a safe
      technique and is suitable for investigations of human breast tissue. Our data
      indicate that metabolism in the breast changes during the menstrual cycle. The
      lower levels of specific amino acids late in the menstrual cycle could indicate a
      higher proliferative and/or apoptotic activity during this period. However, the
      data we have obtained cannot yet be fully explained.

PMID- 9176024
TI  - Raised affinity for extracellular sodium of the sodium-lithium countertransporter
      is associated with a family history of hypertension and uraemia in patients with
      renal disease.
AB  - 1. Increased affinity for sodium (Km) at an external site of the sodium-lithium
      countertransporter and altered membrane microviscosity in the surface regions of
      the lipid bilayer identifies a group of essential hypertensive patients with a
      genetic predisposition to hypertension. The present study investigated the
      kinetic properties of the sodium-lithium countertransporter and membrane
      microviscosity in patients with hypertension, renal disease and impaired renal
      function. 2. Sixty patients with renal disease (28 chronic renal failure, 30
      hypertensive, 23 family history of hypertension) were investigated. Standard
      erythrocyte sodium-lithium countertransport activity, sodium affinity constant
      (Km), maximum reaction velocity (Vmax) and membrane microviscosity were measured.
      3. Patients with renal disease and a family history of hypertension had
      significantly lower Km (P < 0.05) values and raised membrane microviscosity
      measured by 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy (P
      < 0.05) compared with patients without a family history of hypertension. 4.
      Uraemic subjects had low K(m) values compared with patients with renal disease
      and normal renal function (P < 0.05). However, there was no significant
      difference in membrane microviscosity between uraemic and non-uraemic subjects.
      5. In patients with a family history of hypertension, sodium-lithium
      countertransport activity and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5
      hexatriene anisotropy are important markers of cellular changes in essential
      hypertension, independent of renal disease. Uraemia, independently of
      hypertension, produces an alteration in the function of the sodium-lithium
      countertransporter which has previously been associated with a genetic
      predisposition to hypertension and cardiovascular disease.

PMID- 9176025
TI  - Renal afferents responsive to chemical and mechanical pelvic stimuli in the
      rabbit.
AB  - 1. Afferent nerve fibres sensitive to changes in the renal chemical environment
      have been found in the rat. To verify the existence of these fibres in the rabbit
      and their response pattern, afferent renal nerve activity was recorded during
      pelvic perfusions with NaCl solutions at different concentrations. 2. The
      experiments were carried out in 13 anaesthetized rabbits. Arterial pressure from
      a femoral catheter and afferent renal nerve activity from the distal stump of a
      cut renal nerve bundle were recorded. Three catheters were inserted into the
      renal pelvis to measure pelvic pressure, to allow pelvic perfusions at constant
      rates and to drain pelvic fluids. 3. After a control period, the pelvis was
      perfused with physiological saline (0.14 mol/l for 2 min), followed by one of a
      series of solutions containing increasing concentrations of NaCl (0.5, 0.75, 1.0
      and 1.5 mol/l for 2 min). Pelvic perfusion was performed both at a low (0.2
      ml/min) and a high (0.8 ml/min) flow rate for each solution tested. 4. In all
      animals arterial pressure was not modified during pelvic perfusions.
      Physiological saline did not change afferent renal nerve activity at the low
      perfusion rate, but it significantly increased afferent renal nerve activity and
      pelvic pressure at the high rate. Hypertonic NaCl solutions caused progressive
      increases in afferent renal nerve activity at both perfusion rates, and these
      effects were larger at the high perfusion rate. 5. These data demonstrate, in the
      rabbit, the existence of renal afferent nerves sensitive to discrete changes in
      pelvic ionic or osmotic concentration. The neural response is enhanced when renal
      mechano- and chemo-receptors are simultaneously activated.

PMID- 9176026
TI  - HPLC glycosaminoglycan analysis in patients with Graves' disease.
AB  - 1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs)
      and subsequent expansion of retrobulbar tissue lead to the clinical manifestation
      of exophthalmos in patients with Graves' eye disease. 2. A highly specific method
      to determine the concentration and biochemical composition of different GAGs was
      developed in order to obtain a sensitive test system for the activity of the
      disease. By means of this method, GAG excretion in 24 h urine collections of 56
      patients and 21 controls was analysed by precipitation with cetylpyridinium
      chloride and potassium acetate in ethanol, followed by sequential enzymic
      hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate
      lyase, with HPLC analysis of the resulting alpha, beta-unsaturated disaccharides
      by anion-exchange chromatography. 3. Concentrations of GAG, chondroitin sulphate
      A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in
      patients and controls, with high recovery rates [72.2 +/- 5.3%, mean +/- SEM;
      detection limit, 4.2 micrograms/l (0.01 mumol/l)], revealing marked differences
      in urinary concentrations of total GAG and HA, as well as an elevation of CA in
      patients compared with controls. 4. Method sensitivity was 0.86 for patients with
      active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy,
      whereas specificity was 1.0 for patients with inactive disease. Patients with
      increased GAG concentration responded well to steroids and/or orbital irradiation
      (before therapy: GAG, 111.49 +/- 40.32; CA, 59.58 +/- 21.34; DS, 25.05 +/- 8.12;
      HA, 26.88 +/- 11.63 mg/24 h; during therapy: GAG, 54.22 +/- 10.94; CA, 20.52 +/-
      4.58; DS, 17.65 +/- 3.46; HA, 16.05 +/- 3.69 mg/24 h), whereas GAG excretion
      increased markedly 2-3 months after stopping prednisone therapy in patients with
      still active eye disease (GAG, 109.9 +/- 10.51; CA, 63.8 +/- 7.34; DS, 24.1 +/-
      5.07; HA, 22.0 +/- 6.28 mg/24 h). 5. This sensitive method determines the nature
      of renally excreted GAGs, reflecting the aberrant synthesis pattern of
      fibroblasts in patients with Graves' disease.

PMID- 9176027
TI  - Sepsis and endotoxaemia in mice stimulate the expression of interleukin-I and
      interleukin-6 in the central nervous system.
AB  - 1. In previous studies, experimental endotoxaemia was found to stimulate cytokine
      production in the central nervous system. The effect of sepsis on brain cytokines
      is not fully known. We compared the effect of endotoxaemia and sepsis on brain
      interleukin-1 and interleukin-6 expression. 2. Male A/J mice were injected
      subcutaneously with lipopolysaccharide (10 mg/kg) or an equal volume of saline as
      control. Sepsis was induced by caecal ligation and puncture (CLP); control mice
      underwent sham-operation. Brain tissue was assayed for interleukin-1 and
      interleukin-6 by ELISA. Northern blotting or the polymerase chain reaction was
      used to determine cytokine mRNA levels. 3. Administration of endotoxin induced a
      greater than fourfold increase in brain interleukin-1, a greater than threefold
      increase in interleukin-6 and an increase in mRNA for both cytokines. Caecal
      ligation and puncture resulted in increased brain interleukin-1 and interleukin-6
      levels, but the changes were less pronounced and occurred later than after
      injection of endotoxin. There was no detectable difference in brain interleukin-1
      mRNA between septic and sham-operated mice, whereas interleukin-6 mRNA was
      increased in brains of septic animals. 4. Sepsis and endotoxaemia resulted in
      similar, although not identical, changes in brain interleukin-1 and interleukin-6
      concentrations and mRNA levels, suggesting that increased cytokine production in
      the central nervous system is part of the systemic response to sepsis and may be
      mediated by endotoxin.

PMID- 9176028
TI  - Impaired cytokine production by peripheral T lymphocytes in low responders to
      hepatitis B vaccination.

PMID- 9176029
TI  - Gene therapy for diabetes mellitus.
AB  - 1. This review describes experimental approaches to test the feasibility of using
      gene therapy to administer insulin to type 1 and type 2 diabetic patients. Two
      approaches, i.e. ex vivo and in vivo transfer of the insulin gene, are described.
      2. Substantial progress has been made in recent years in engineering glucose
      responsive beta-cell lines that have been genetically engineered to proliferate
      or differentiate in response to appropriate extracellular signals. 3. Non-beta
      cell lines have been engineered to constitutively secrete insulin at a constant
      rate. These cells may improve glycaemic control in patients over longer periods
      when used in combination with insulin injections. Engineering glucose-stimulated
      insulin secretion in such cells has proved extremely difficult and several genes
      may he required. 4. In vivo transfer of the insulin gene to animals results in
      improved control of diabetes. However, for safety reasons this approach may have
      limited use in the treatment of diabetes in humans.

PMID- 9176030
TI  - Could the A2A11 human leucocyte antigen locus correlate with maximal aerobic
      power?
AB  - 1. The power of the aerobic metabolic pathway correlates well with successful
      physical performance in endurance sports events. The ability to alter the pathway
      through training presents well-known limitations, and consequently a good genetic
      endowment is essential to participate in elite sporting activities. 2. In 32
      subjects (16 healthy pairs of male twin sportsmen, 8 monozygotic and 8 dizygotic)
      zygosity was determined by means of the genetic analysis of human leucocyte
      antigen (HLA) system specificities at class I and II loci and other genetic
      variants. The subjects performed a progressive exercise test on a treadmill to
      ascertain the maximal oxygen uptake (VO2max), measured by an automatic breath-by
      breath analyser. We have considered the relationship between the A, B and C loci
      of the HLA system and VO2max. 3. We found a high correlation between the presence
      of both HLA A2 and A11 and VO2max. In the A2A11 group (n = 6) we found a VO2max
      (mean +/- SD) equal to 71 +/- 4 ml min-1 kg-1. The group without this pair of
      alleles (n = 26) showed a much lower aerobic power (58 +/- 5 ml min-1 kg-1).
      Differences between the two groups were found to be largely significant (P <
      0.001). It is noteworthy that in two pairs of dizygotic twins, the higher VO2max
      value corresponded to the twin with the A2A11 allele. 4. The very marked
      concordance between the presence of the A2A11 locus of the HLA system and the
      VO2max could be of great interest for the identification of outstanding
      performers.

PMID- 9176031
TI  - Heart rate variability in patients with daytime sleepiness suspected of having
      sleep apnoea syndrome: a receiver-operating characteristic analysis.
AB  - 1. Periodic breathing is known to be associated with cyclic fluctuations in heart
      rate. The purpose of this study was to evaluate the capability of spectral
      analysis of heart rate variability to identify episodes with periodic breathing
      in patients suspected of having sleep apnoea syndrome. 2. Forty-eight subjects
      complaining of chronic day-time sleepiness were studied using polysomnography and
      additional monitoring of Holter-ECG and synchronized pulse oximetry. The
      recordings were divided into 20 min episodes which were identified as recordings
      registered during normal breathing, periodic breathing, and periods of both
      normal and abnormal breathing. Power spectral analysis was performed on episodes
      which met the criteria of stationary of data (313 episodes with normal breathing,
      264 episodes with continuous periodic breathing, 80 episodes with both normal and
      periodic breathing patterns). 3. The ability of parameters, derived from analysis
      of heart rate variability, to discriminate between episodes with normal and
      periodic breathing was assessed by receiver-operating characteristic analysis. 4.
      The spectral power component in the frequency range 0.01-0.07 Hz revealed the
      greatest accuracy for discriminating between normal and periodic breathing (area
      under the receiver-operating characteristic curve = 0.929; standard error =
      0.009). The analysis of the episodes classified as false-positive at a given test
      sensitivity of 90% and a corresponding specificity of 77% revealed that half of
      these episodes had been recorded during transient central nervous arousal
      reactions related to periodic leg movements or heavy snoring. 5. We concluded
      that power spectral analysis of heart rate variability offers a possible means of
      identifying episodes of sleep-related breathing disorders or periodic leg
      movements. Therefore, analysis of heart rate variability may be a valuable
      additional diagnostic tool in patients undergoing Holter-ECG recording.

PMID- 9176032
TI  - Complementary and non-coincident increases in heart rate variability and
      irregularity during fetal development.
AB  - 1. Two distinct notions of variability have been defined to assess heart rate:
      deviation from a constant output (SD) and irregularity. One statistical measure
      of irregularity is approximate entropy, with greater irregularity corresponding
      to larger approximate entropy values. The specific aims of this investigation
      were to determine the manner in which SD and irregularity evolve during fetal
      development and whether this evolution is coincident or distinct. 2. Fetal heart
      rate was computed in 14 males and 17 females for 15 min of undisturbed recording
      using a fetal actocardiograph at 4 week intervals from 20 to 36 weeks gestation.
      3. Mean heart rate decreased significantly with gestational ages (P < 0.05). SD
      increased significantly from 4.4 +/- 0.3 ms (SEM) at 20 weeks to 7.7 +/- 0.4 ms
      at 36 weeks (P < 0.05) and was similar between male and female fetuses (P =
      0.57). Fixed approximate entropy increased significantly from 0.47 +/- 0.04 to
      0.78 +/- 0.03, paralleling the change in SD (P < 0.01). Notably, normalized
      approximate entropy, which decorrelates SD from regularity, increased
      significantly with gestational age (P < 0.01) for males, while it remained
      relatively constant for females (P = 0.68). Approximate entropy was significantly
      lower at 20 weeks in males than females (P < 0.05); however, the values were
      similar by 28 weeks gestation. 4. Our results demonstrate that variability
      increases, and that irregularity increases, independently in male fetuses but not
      female fetuses, consistent with an increase in the coupling of emerging networks
      with gestational age. The present study demonstrates the complementary
      information obtained by analyses of both measures of variability and regularity.
      This reinforces a difference in gender-based development as noted in the separate
      context of fetal lung maturation.

PMID- 9176033
TI  - Autonomic nervous function during haemodialysis assessed by spectral analysis of
      heart-rate variability.
AB  - 1. Short-term autonomic response to haemodialysis-induced hypovolaemia was
      studied in 30 patients undergoing chronic haemodialysis by analysing power
      spectra of heart-period variability. Patients were classified as haemodynamically
      stable (15 patients) and unstable (15 patients) according to their past history
      of cardiovascular collapse during the treatment. Blood volume, systolic arterial
      pressure and heart period were measured during sessions that ended without the
      occurrence of collapse. 2. No significant differences were observed when
      comparing blood volume, heart rate and arterial pressure of stable and unstable
      patients during the dialysis, and the two groups could not be distinguished
      merely on the basis of these haemodynamic parameters. Conversely, spectral
      analysis of beat-to-beat heart-period variability showed markedly different power
      patterns: in stable patients power was mainly in the low-frequency (LF) band
      (0.06-0.15 Hz), whereas in unstable patients it was mainly in the high-frequency
      (HF) band (0.15-0.4 Hz). 3. The efficiency of the autonomic response to
      hypovolaemia was evaluated by the ratio between the powers in the LF and HF
      bands. Stable patients exhibited an LF/HF power ratio systematically greater than
      unstable patients during the entire dialysis, and on the basis of this index the
      two groups were clearly separated. 4. Results obtained with spectral analysis
      lead us to conclude that reduced efficiency in the autonomic control of
      cardiovascular functions could be the main cause of the haemodynamic instability
      of patients prone to collapse.

PMID- 9176034
TI  - Combination oral antioxidant supplementation reduces blood pressure.
AB  - 1. Hypertension affects 30% of adults and low intakes of antioxidants have been
      associated with increased risk of hypertension and cardiovascular disease. To
      investigate the effect of short-term high-dose antioxidant supplementation on
      blood pressure in hypertensive and normotensive outpatients, we undertook a
      randomized, double-blind, crossover design placebo-controlled study. 2. Forty
      subjects were recruited from medical outpatient clinics, of whom 38 completed the
      study. Twenty-one were attending for treatment of hypertension and 17 were
      normotensive, attending for minor gastrointestinal complaints. Subjects were
      randomly assigned to receive either 8 weeks placebo followed by 2 weeks washout
      then 8 weeks antioxidants or vice versa. The combination of antioxidants
      consisted of 200 mg of zinc sulphate, 500 mg of ascorbic acid, 600 mg of alpha
      tocopherol (sodium succinate salt) and 30 mg of beta-carotene daily. 3. Systolic
      blood pressure fell at the end of the antioxidant phase compared with the placebo
      phase both in subjects receiving anti-hypertensive therapy (P < 0.01) and those
      who were normotensive (P = 0.067). Circulating levels of beta-carotene and alpha
      tocopherol increased in all subjects during supplementation (P < 0.01) and urine
      nitrite increased in hypertensive patients (P < 0.05). 4. Short-term oral high
      dose combination antioxidant therapy reduces blood pressure, possibly via
      increased availability of nitric oxide. This study may have implications for the
      innovative use of antioxidants as an adjunct to anti-hypertensive therapy.

PMID- 9176035
TI  - Haemodynamic and biochemical responses to L-arginine and L-lysine infusions in
      normal subjects: L-arginine-induced vasodilatation cannot be explained by non
      specific effects of cationic amino acids.
AB  - 1. Pharmacological stimulation of the synthesis of nitric oxide (NO) may be
      important in the prevention or treatment of cardiovascular diseases. 2. There is
      much discussion as to whether the precursor of NO, L-arginine, is able to
      stimulate basal endothelial NO production. L-Arginine is known to have
      vasodilating effects. However, it is not clear whether L-arginine-induced
      vasodilatation is attributable to an increase in NO production or to other
      systemic effects of L-arginine. 3. To investigate further the mechanisms of the L
      arginine-induced vasodilatation, we compared the responses to L-arginine with
      those to saline and L-lysine in healthy subjects. L-Lysine is not a substrate for
      NO synthesis, but shares many of L-arginine's other properties. 4. During L
      arginine infusion, blood pressure decreased [systolic blood pressure from 120.2
      (SD 8.8) to 117.3 (12.1) mmHg (P = 0.05); diastolic blood pressure from 65.3
      (5.9) to 61.6 (7.9) mmHg (P < 0.01)], and heart rate and extracellular fluid
      volume increased. The total peripheral vascular resistance decreased during L
      arginine infusion by 18.0 (11.4)% (P < or = 0.05 compared with baseline and
      compared with L-lysine infusion). These results indicate vasodilation. No changes
      were observed during L-lysine and saline infusion. 5. Plasma cyclic GMP (the
      second messenger for NO) increased during L-arginine but also during L-lysine
      infusion [from 5.7 (1.2) to 6.8 (1.7) nmol/l (P < 0.01), and from 5.8 (1.8) to
      7.0 (2.9) nmol/l (P < 0.05) respectively]. Plasma L-citrulline (a by-product of
      NO synthesis from L-arginine) increased during L-arginine infusion from 30.6
      (7.5) to 47.1 (9.9) mumol/l (P < 0.001), but also during L-lysine infusion from
      32.7 (6.5) to 42.0 (8.3) mumol/l (P < 0.001). 6. Plasma electrolytes and atrial
      natriuretic peptide concentrations responded similarly to L-arginine and L-lysine
      infusion, indicating similar effects on osmolality, plasma volume expansion and
      potassium distribution. 7. In conclusion, although L-lysine infusion had effects
      that were similar to those of L-arginine infusion, no vasodilatation was
      observed. Therefore, these effects cannot account for the L-arginine-induced
      vasodilatation. This finding indirectly supports the hypothesis that the
      vasodilatation during L-arginine infusion might be mediated by an increase in NO
      synthesis. If so, our data suggest that the presumed markers for NO synthesis,
      plasma cyclic GMP and L-citrulline concentrations, do not accurately reflect this
      increase. Instead, the rise in plasma cyclic GMP may be related to the rise in
      ANP. The rise in L-citrulline may be related to competition with L-arginine for
      the same cell membrane transport mechanism and to stimulation of the urea cycle.

PMID- 9176036
TI  - The steroid vitamin D3 reduces cell proliferation in human duodenal epithelium.
AB  - 1. The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, controls
      calcium absorption in the human duodenum, an effect that is mediated by mucosal
      vitamin D receptor expression. Functional vitamin D receptor signalling in the
      human colon is suggested by the reduced colonic mucosal cell proliferation seen
      in response to 1,25-dihydroxyvitamin D3. Thus 1,25-dihydroxyvitamin D3 might be
      expected to reduce cell proliferation in the small-bowel epithelium. 2. We have
      used an organ-culture system combined with the metaphase arrest technique to
      study the effects of 1,25-dihydroxyvitamin D3 on human duodenal mucosal
      proliferation. To validate our technique, multiple human mucosal explants were
      established in organ culture and vincristine (0.6 micrograms/ml) was added at 10
      h. Explants were removed sequentially from 10 to 15 h and metaphase arrest
      figures were demonstrated by using the Feulgen reaction. The mean number of
      metaphase arrest figures was plotted against time in culture to show a linear
      accumulation of metaphases between 11 and 15 h (correlation coefficient = 0.93,
      r2 = 0.87, P < 0.0001). The mean crypt cell production rate was 2.01 (0.27)
      cells/h per crypt. 3. Paired normal duodenal mucosal biopsies from six patients
      were then established in organ culture with or without 10(-10) mol/l (100 pmol/l)
      1,25-dihydroxyvitamin D3. The crypt cell production rate was determined between
      12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxyvitamin D3
      reduced the median crypt cell production rate from 2.42 (1.15-4.82) to 1.41 (0.03
      2.05) cells/h per crypt (P < 0.05). Thus, vitamin D3 reduces human duodenal
      epithelial cell proliferation.

PMID- 9176037
TI  - Intestinal absorption of trace amounts of aluminium in rats studied with
      26aluminium and accelerator mass spectrometry.
AB  - 1. Until recently studies of intestinal aluminium absorption used pharmacological
      amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts
      of different chemical compounds of aluminium, in the present study we have
      employed the long half-life isotope of aluminium, 26Al, and accelerator mass
      spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate,
      citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were
      administered to four groups of rats (n = 9 per group) by gavage. Blood and urine
      samples were collected for 5 h and the 26Al content (as a percentage of the
      administered dose) determined by accelerator mass spectrometry. 3. The 5 h
      urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1
      +/- 0.1% of administered dose in the four groups respectively. There was a strong
      positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al
      excretion in individual animals (P < 0.001). 4. We conclude that the fractional
      intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1%
      (compared with the previous estimate of 0.01% using large 27Al oral loads).
      Absorption of aluminium citrate given alone is significantly greater (0.7%) and
      is further increased to 5% by the accompanying sodium citrate, consistent with an
      enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium
      maltolate absorption approximates that of aluminium hydroxide (0.1%).

PMID- 9176038
TI  - Effect of high-dose chemotherapy on intestinal permeability in humans.
AB  - 1. Mucositis is a common side-effect of chemotherapy which is difficult to assess
      except by invasive means such as upper gastrointestinal endoscopy. Differential
      absorption of mono- and di-saccharides, such as rhamnose and lactulose, is a non
      invasive measure of intestinal damage. 2. The purpose of the study was to assess
      the duration and severity of intestinal damage in patients undergoing high-dose
      chemotherapy and autologous blood stem-cell transplantation for malignant
      disease. 3. Thirty-five patients were studied before treatment and at 7, 28, 60
      and 90 days after treatment. 4. The median lactulose/rhamnose ratios before
      treatment and at 7 and 90 days post-treatment were 0.09, 0.62 and 0.06
      respectively. Altered permeability was due to both increased lactulose permeation
      and decreased rhamnose absorption. These abnormalities suggest a defect in tight
      junction integrity as well as a decrease in surface area of small bowel. 5. We
      conclude that chemotherapy given for malignant disease is associated with a
      transient abnormality in intestinal sugar permeability, which peaks at 7 days
      after treatment and is composed of both mono- and di-saccharide absorption
      abnormalities.

PMID- 9176039
TI  - Resting membrane potential of skeletal muscle calculated from plasma and muscle
      electrolyte and water contents.
AB  - 1. A method is described that enables the calculation of resting membrane
      potential from the electrolyte and water contents in blood plasma and in a sample
      of human muscle tissue obtained by the percutaneous needle-biopsy technique. In
      this calculation, the previously described equations for calculating resting
      membrane potential via the intra- and extra-cellular distribution of chloride
      were combined with the equation utilizing potassium distribution over the cell
      membrane. 2. The method of calculation was applied to 60 healthy subjects divided
      into three groups aged 19-40, 41-60 and 61-85 years. The calculated resting
      membrane potential in the subjects as a whole was -88.4 mV (SD 1.35; n = 60). A
      lower value was observed in the group aged 61-85 years (-87.7 mV, SD 1.0; n = 12)
      than in the group aged 19-40 years (-88.6 mV; SD 1.4; n = 32). No difference was
      observed between female and male subjects. 3. The RMP calculated with the present
      method in 60 healthy subjects was also compared with previously published values
      in healthy subjects, measured by the Clarke electrode method, and with values
      calculated from electrolyte and water distribution measured by isotope-dilution
      techniques. The results obtained in healthy subjects with different techniques
      were very similar. Data were analysed from earlier published studies in
      experimental animals in which resting membrane potential ranged from -91 to -65
      mV. The resting membrane potential calculated from electrolytes in plasma and
      muscle showed a very good agreement with resting membrane potential recorded
      directly.

PMID- 9176040
TI  - Effect of urodilatin infusion on renal haemodynamics, tubular function and
      vasoactive hormones.
AB  - 1. The renal efficacy of urodilatin in humans has only been partly investigated.
      It is unknown whether intravenously infused urodilatin has an effect on sodium
      reabsorption in both the proximal and distal part of the nephron. 2. Twelve
      healthy subjects participated in this double-blind, placebo-controlled study in a
      cross-over design. They received, in a randomized order, a short term (60 min)
      infusion of urodilatin in three different doses (10, 20 and 40 ng min-1 kg-1 of
      body weight) and placebo. Renal haemodynamics were estimated by clearance
      technique with radioactive tracers, and proximal tubular handling of sodium was
      evaluated by lithium clearance. 3. The 20 ng min-1 kg-1 dose increased the
      urinary sodium excretion and urinary flow rate compared with the effects of
      placebo. It increased the glomerular filtration rate and decreased the effective
      renal plasma flow. In addition, the dose increased the lithium clearance compared
      with placebo, but did not significantly change the fractional excretion of
      lithium. On the other hand, it markedly decreased the distal fractional
      reabsorption of sodium. It also had a suppressive effect on renin secretion. The
      systemic arterial blood pressure was unchanged, but the dose increased the pulse
      rate and the haematocrit. The highest dose (40 ng min-1 kg-1) induced a wide
      variation in the natriuretic and diuretic responses, probably due to a blood
      pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min-1
      kg-1 of body weight was most efficacious in this short-term infusion study, and
      that it had potent natriuretic and diuretic qualities, probably due to
      stimulation of the glomerular filtration rate and inhibition of sodium
      reabsorption in the distal part of the nephron.

PMID- 9176041
TI  - Comparison of the effects on urinary sodium excretion of indomethacin and of
      carbidopa in normal volunteers given an intravenous saline infusion.
AB  - 1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The
      role of each in facilitating natriuresis induced by intravenous saline infusion
      was examined in normal volunteers in relation to administration of carbidopa, a
      dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin
      synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received
      carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal
      renal tubular Na+ reabsorption were determined using exogenous lithium clearance.
      3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously
      in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the
      urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no
      effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and
      increased distal fractional Na+ reabsorption in proportion to the antinatriuretic
      effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial
      natriuretic peptide and renin activity associated with volume expansion were not
      modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion
      was decreased transiently by indomethacin and was unaffected by carbidopa. 5.
      This study suggests that prostaglandins may modulate urinary Na+ excretion during
      saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption.
      No role for free dopamine as a modulator of renal Na+ handling could be assigned
      on the basis of the findings with carbidopa.

PMID- 9176042
TI  - Mild endotoxaemia and the inflammatory response induced by a marathon race.
AB  - 1. To address the question of whether endotoxaemia could be involved in the
      inflammatory response induced by long-term strenuous exercise, 18 male marathon
      runners [mean age 41 +/- 2 (SEM) years] were studied. Their performance in the
      marathon ranged from 2 h 46 min to 4 h 42 min. 2. Four venous blood samples were
      drawn: at rest, just before the race (baseline); within 15 min following the
      completion of the marathon; after 1 h of recovery; and the morning after the
      race. 3. The following humoral markers of the inflammatory response to exercise
      were measured: polymorphonuclear myeloperoxidase (MPO), anaphylatoxin C5a (C5a),
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Plasma
      endotoxin was measured by a sensitive and rapid chromogenic Limulus assay. All
      inflammatory markers were significantly increased (P < 0.001) after the race,
      reaching in most cases peak values in the first blood sample drawn following the
      completion of the marathon [MPO, 298 +/- 19 ng/ml (SEM); C5a, 1.45 +/- 0.32
      ng/ml; TNF-alpha, 20 +/- 3 pg/ml; IL-6, 88 +/- 13 pg/ml] when compared with
      baseline [MPO, 146 +/- 16 ng/ml (SEM); C5a, 0.27 +/- 0.2 ng/ml; TNF-alpha, 12 +/-
      1.5 pg/ml: IL-6, 1.0 +/- 0.5 pg/ml]. Traces of plasma endotoxin (ranging from 5
      to 13 pg/ml, with one exceptionally high value of 72 pg/ml measured in one
      runner) were detected in seven subjects within the first hour of recovery. An
      ELISA method was used to determine the endogenous IgG antibodies toward a range
      of Gram-negative bacterial lipopolysaccharides (LPSs) of different sizes and
      structures. A transient decrease in certain anti-LPS activities, mainly against
      rough LPS, occurred in most cases in the first blood sample drawn after the race.
      There was no correlation between the magnitude of the inflammatory response to
      exercise, as assessed by the increase in blood levels of humoral markers of
      inflammation, and the changes in circulating endotoxin levels of anti-LPS IgG
      activity following the race. 4. From these results, we conclude that the mild,
      transient endotoxaemia detected in some of our subjects does not play a major
      role in the observed inflammatory response to a marathon competition.

PMID- 9176043
TI  - Effects of ordinary meals on plasma concentrations of 3,4-dihydroxyphenylalanine,
      dopamine sulphate and 3,4-dihydroxyphenylacetic acid.
AB  - 1. Plasma concentrations of 3,4-dihydroxyphenylalanine (DOPA), dopamine sulphate
      (DA-S), and 3,4-dihydroxyphenylacetic acid (DOPAC) in humans have been claimed to
      be indexes of sympathetic nervous activity, but the source and significance of
      plasma DOPA, DOPAC and DA-S have not been completely elucidated. 2. The effects
      of ordinary meals on plasma concentrations of total dopamine, mainly DA-S, DOPAC
      and DOPA were studied in seven healthy subjects. Venous blood was collected every
      hour for 25 h, while subjects were either fasting or received three meals at 9.00
      hours, 13.00 hours and 18.00 hours. Catecholamines and metabolites were
      determined by reverse-phase HPLC with electrochemical detection. Neutral amino
      acids were measured by ion-exchange chromatography with photometric detection. 3.
      The food contained relatively little DOPA as compared with phenylalanine,
      tyrosine, isoleucine and tryptophan. The content of DA and DA-S varied
      considerably, with the greatest amount in the evening meal of open sandwiches. 4.
      Plasma DOPA decreased significantly after the meals at 13.00 hours and 18.00
      hours, whereas concentrations of the other amino acids increased as expected. 5.
      Plasma DA-S increased significantly after meals and especially after the evening
      meal. Increments in DA-S above basal values after a meal were closely related to
      the content of DOPA+DA+DA-S in the meal. Plasma DOPAC increased significantly
      after the evening meal. 6. The decrease in plasma DOPA observed after a meal was
      probably due to uptake of DOPA by muscle tissue. Changes in plasma DA-S and DOPAC
      during this 25-h study reflected to a large extent the content of DOPA, DA and DA
      S in the meals.

PMID- 9176044
TI  - Lipid-lowering strategies for the prevention of coronary heart disease.

PMID- 9176045
TI  - Distribution of endothelin and endothelin-A receptor in the lacrimal glands of
      the monkey (Macaca fuscata).
AB  - Endothelin (ET) is well known to be a potent vasoconstrictor peptide with
      autocrine and paracrine function. It has been documented that ET is also present
      in non-muscle tissues. The distribution of ET and ET-A receptor (ET-AR) in the
      monkey lacrimal gland was investigated by immunohistochemistry. Three adult male
      monkeys (Macaca fuscata) were perfused with a fixative. The lacrimal glands were
      then dissected and sectioned. Using rabbit anti-ET and anti-ET-AR antibodies, the
      immunohistochemical procedure was performed following an ABC technique. Some
      sections were treated with rhodamine-phalloidin, which selectively binds to actin
      filaments. ET immunoreactivity was present in stellate-shaped cells located
      around the alveoli. In sections double-stained with anti-ET antibody and
      rhodamine-phalloidin, ET immunoreactivity and abundant filamentous actin were
      identified in the same stellate cells. Immunostaining for ET-AR was also found in
      the stellate shape cells. The configuration of, and the abundance of actin
      filaments in the stellate-shaped ET- and ET-AR immunoreactive cells suggest that
      they are myoepithelial cells, which are contractile and may contribute to the
      process of lacrimal gland secretion or maintenance of the contour of the
      glandular endpieces. Our results indicate that endothelin is present in
      myoepithelial cells of the monkey lacrimal gland.

PMID- 9176046
TI  - Tissue culture of retinal pigment epithelium following isolation with a gelatin
      matrix technique.
AB  - Prior to transplantation of the retinal pigment epithelium, it is necessary to
      develop techniques to harvest viable retinal pigment epithelium as an organized
      monolayer. Unfortunately, current techniques result in contraction of the
      harvested monolayer and coiling of the cell sheets, which hinders successful
      transplantation. The purpose of this study was to develop a method for harvesting
      retinal pigment epithelium from eye cups and from tissue culture prior to
      transplantation. Passage 1 porcine retinal pigment epithelium and native retinal
      pigment epithelium from fresh porcine eye cups were pretreated with 0.25% edetic
      acid for 12 minutes and coated with a 100 micron layer of 12% gelatin. Patches of
      the retinal pigment epithelial cell monolayer were harvested and transferred to
      culture plates, and cell viability and the ability of the transferred cells to
      proliferate in culture was determined. Our results demonstrated that retinal
      pigment epithelium can be harvested from tissue culture and eye cups as an
      organized monolayer with high efficiency (94.7 +/- 3.5% and 99.7 +/- 0.3%
      harvesting rates, respectively) and high cell viability (91.3 +/- 2.9% and 89.4
      +/- 4.3%, respectively). Cells harvested from tissue culture plates divided and
      became confluent within 10 to 14 days. Cells harvested from eye cups maintained a
      differentiated phenotype and migrated outward from the margin of the exoplant.
      There was no contraction of the retinal pigment epithelial monolayer isolated
      from either substrate. Thus, we were able to harvest retinal pigment epithelium
      as an organized monolayer from tissue culture plates and freshly enucleated eyes
      with edetic acid and gelatin. The harvested cells were viable and proliferated
      without contraction of the monolayer in vitro.

PMID- 9176047
TI  - Cholinergic stimulation of lacrimal acinar cells promotes redistribution of
      membrane-associated kinesin and the secretory protein, beta-hexosaminidase, and
      increases kinesin motor activity.
AB  - The role of the microtubule-based motor, kinesin, in membrane trafficking has
      been investigated in resting and stimulated acinar cells from rabbit lacrimal
      gland, a cholinergically controlled secretory tissue. Microtubule-dependent
      motors from extracts of control and carbachol-treated acini were isolated by
      microtubule-affinity purification and their activity was determined using a video
      enhanced differential interference contrast microscopy assay for microtubule
      gliding. The observation that carbachol treatment resulted in a 2.2-fold
      stimulation of the frequency of GTP-dependent microtubule gliding in fractions
      isolated by microtubule-affinity purification and GTP release suggested that
      kinesin was a target of carbachol-induced stimulation. Resolution of membranes
      from resting cells by fractionation on a sorbitol density gradient followed by
      partitioning analysis in a dextran-polyethyleneglycol two-phase system revealed
      that membrane-associated kinesin codistributed with Golgi-derived membranes, a
      post-Golgi secretory compartment designated Hex1, membranes from a trans Golgi
      network-like compartment, endoplasmic reticulum and a group of putative lysosomal
      membranes containing cathepsin B. Comparable fractionation of carbachol-treated
      acini showed that stimulation caused redistributions of membrane-associated
      kinesin, the secretory enzyme beta-hexosaminidase, and galactosyltransferase that
      appeared to reflect both a reorganization within the Golgi complex and a return
      of material to the Golgi complex from the secretory pathway. Our findings that
      carbachol promotes activation of lacrimal acinar kinesin as well as major shifts
      in kinesin-membrane association within the secretory pathway suggests that
      kinesin plays a major role in secretory vesicle assembly, apical secretion,
      and/or secretory vesicle membrane recycling in the lacrimal gland.

PMID- 9176048
TI  - Inhibition of glutamate uptake causes an acute increase in aqueous humor protein.
AB  - Inhibition of glutamate transport has been shown to increase paracellular
      permeability of epithelial cell monolayers in vitro. To determine if blocking
      glutamate transport would affect tissue permeability in vivo, D-aspartate (D-Asp;
      300 nmol 30 microliters-1) (a non-toxic competitive inhibitor of glutamate
      transport) or a placebo was injected into the anterior chambers of the fellow
      eyes of 15 adult rabbits. [14C]-L-glucose and/or [125I]-rabbit albumin were
      included in the injection vehicle as aqueous humor (AH) outflow markers. The
      specific inhibition of glutamate uptake by D-Asp was indicated by a 15% increase
      in AH glutamate (174 +/- 9 nmol ml-1 to 205 +/- 13 nmol ml-1; P = 0.03) at 1-1.5
      hr post injection. Also, the efflux of [14C]-L-glucose and [125I]-rabbit albumin
      from the AH of D-Asp injected eyes was increased 22% over the placebo-injected
      control eyes (P < or = 0.02). Concomitantly, the total protein concentration in
      the AH from D-Asp injected eyes (517 +/- 35 micrograms ml-1) was 19% greater (P <
      0.02) than the protein concentration in AH from placebo-injected control eyes
      (420 +/- 36 micrograms ml-1). In additional studies, an irreversible inhibitor of
      glutamate transport, threo-beta-hydroxyaspartate (THA; 30 nmol 30 microliters-1),
      was shown to increase the efflux of [14C]-L-glucose (22%; P < 0.05) from the
      anterior chamber and increase AH protein concentrations by 29% (484 +/- 112
      micrograms ml-1 in control AH versus 686 +/- 117 micrograms ml-1 in THA AH, P =
      0.08) at 1 hr post intracameral injection. SDS-PAGE analysis of the AH associated
      the protein increase in the D-Asp and THA injected eyes but not placebo-injected
      control eyes with a detectable increase in a 66 kDa protein (aligns with serum
      albumin) and several lower molecular weight (23-35 kDa) AH proteins. The results
      found suggest that inhibition of glutamate transport from the AH acutely
      increases intraocular epithelial/endothelial paracellular permeability.

PMID- 9176049
TI  - Effect of long-term topical betaxolol on tissue circulation in the iris and optic
      nerve head.
AB  - The effect of long-term topical betaxolol on tissue circulation in the iris and
      optic nerve head was studied. Twenty microliters of 0.5% betaxolol ophthalmic
      solution was instilled in one eye of an albino rabbit and the same amount of
      physiological saline in the fellow eye twice daily for 20 days. A quantitative
      index of tissue blood velocity, NB value, was measured in the iris (21 rabbits)
      and optic nerve head (31 rabbits) of both eyes before the first instillation and
      2 hr after completion of instillations, using a laser speckle tissue circulation
      analyser of which details have been reported previously. The intraocular pressure
      was also measured at 5-day intervals. The intraocular pressure was lowered by 2-3
      mmHg only in the betaxolol-treated eye (P < 0.01). Both in the iris and optic
      nerve head no significant bilateral difference in the NB was seen before the
      first instillation, while it was significantly greater in the betaxolol-treated
      than in the contralateral control eye by about 10% after completion of
      instillations (P < 0.02-0.05). The difference between the NB after completion of
      instillations and that before the first instillation was significantly greater in
      the betaxolol-treated eye than in the contralateral control eye both in the iris
      and optic nerve head (P < 0.001-0.02). Twenty-day twice daily instillation of
      0.5% betaxolol caused relatively small, but significant increase in tissue blood
      velocity in the ipsilateral iris and optic nerve head in albino rabbits, which
      may have clinical implications.

PMID- 9176050
TI  - Synergistic increase in Ca2+ produced by A1 adenosine and muscarinic receptor
      activation via a pertussis-toxin-sensitive pathway in epithelial cells of the
      rabbit ciliary body.
AB  - The combined effects of adenosine and acetylcholine on the intracellular free
      Ca2+ concentration in nonpigmented epithelial cells of the rabbit ciliary body
      were investigated using fura-2 fluorescence-ratio imaging. Acetylcholine (10
      microM) by itself produced a modest increase in [Ca2+]i. Acetylcholine in
      combination with adenosine, or with the A1-specific agonists N6-cyclohexyl
      adenosine, N6-cyclopentyl-adenosine and (R)-N6-(2-phenyl-1-methylethyl)-adenosine
      (0.1-1 microM), induced a massive increase in [Ca2+]i, which could be blocked by
      the A1-specific antagonist 8-cyclopentyl-1,3-dipropylxanthine. However, the A2
      specific agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-ade
      nos ine and the antagonist 3,7-dimethyl-1-(2-propynyl)xanthine were without
      effect. Incubation of the tissue with pertussis toxin did not alter the response
      to ACh alone but eliminated the synergistic effect of adenosine (or of
      epinephrine). It was concluded that in the epithelial cells of the rabbit ciliary
      body, adenosine and epinephrine synergistically potentiate the rise in [Ca2+]i
      produced by ACh. This potentiation appears to occur via a pertussis-toxin
      sensitive pathway, perhaps through G(i).

PMID- 9176051
TI  - Lipids of plasma, retina, and retinal pigment epithelium in Swedish briard dogs
      with a slowly progressive retinal dystrophy.
AB  - Reduced blood levels of long chain polyunsaturated fatty acids have been reported
      in humans and animals with inherited retinal degenerations. The lipid and fatty
      acid compositions of plasma, retina, and retinal pigment epithelium of the
      Swedish Briard dog, which has a very slowly progressive retinal dystrophy that is
      inherited in an autosomal recessive manner were analysed. The lipid class
      composition of the pigment epithelium was not different between affected and
      normal dogs; however, significant differences were found between the retinas of
      the two groups. Affected dogs had relatively more phosphatidylethanolamine and
      phosphatidylinositol and less phosphatidylcholine than normal dogs. There was no
      difference in the fatty acid compositions of plasma and retinal pigment
      epithelium between affected and normal dogs. However, the retinas of affected
      dogs had significantly lower levels of 22:5n-3 and 22:6n-3 and higher levels of
      18:2n-6, 20:4n-6, and 22:5n-6. The total n-3 fatty acid content was significantly
      lower in affected retinas (P < 0.001), whereas the content of n-6 fatty acids was
      significantly higher in affected retinas (P < 0.001). These studies provide
      evidence for yet another animal model of inherited retinal degeneration with a
      defect in retinal polyunsaturated fatty acid metabolism. The fatty acid pattern
      in affected dogs resembles that seen in the retina in n-3 fatty acid deficiency.

PMID- 9176052
TI  - Lenticular scattered and fluorescent light: biomicroscopic determination of their
      relative proportions.
AB  - Lenticular fluorescence was separated from scattered light using slit-lamp
      photography through two different spectral filters. The results from 10 subjects
      indicate that the cortex and nucleus show different rates of age-related change
      in fluorescence. Evidence was obtained for the presence of more than one
      fluorophor.

PMID- 9176053
TI  - In experimental diabetes the decrease in the eye of lens carnitine levels is an
      early important and selective event.
AB  - Carnitine is present in the eye tissues of the rabbit and the highest
      concentration is found in the lens. In streptozotocin-diabetic rats, the
      carnitine loss of the lens is an initial and important event. At 8 days after the
      induction of diabetes, the carnitine content in the rat lens was reduced by 63%
      compared to control. The loss of lens carnitine continued at 15 and 45 days after
      the induction. Total carnitine level in the serum was diminished by 15 days, and
      the reduction in percentage term was much lower in comparison to the loss of lens
      carnitine. In the rabbit after alloxan-diabetes induction, there is an extensive
      loss of carnitine in the lens: -85% after 4 months. The carnitine levels in the
      other eye tissues seem substantially unaffected. The loss of lens carnitine was
      present even with an inconsistent hyperglycaemia. No difference was found in
      serum carnitine levels between controls and alloxan-treated rabbits. The role of
      carnitine in lens is still unclear, but its loss may be related to the appearance
      of cataract. A derivative of carnitine, acetylcarnitine, might prevent the
      processes involved in the formation of cataracts by a pharmacological action, as
      has been shown for aspirin.

PMID- 9176054
TI  - Expression of aquaporins in the rat ocular tissue.
AB  - The aquaporins (AQPs) are a rapid growing family of water channel proteins found
      in animals, plants and microorganisms that raise plasma membrane water
      permeability required for efficient isosmotic fluid transport. Five homologs of
      aquaporins (AQP1, AQP2, AQP3, AQP4 and AQP5) have been identified from various
      mammalian tissues; the expression of these aquaporins in ocular tissues was
      studied. Semiquantitative expression levels of these aquaporins were determined
      in ciliary body, cornea, lens, retina, iris and choroid using RT-PCR. Expression
      levels of AQP1 are highest among the known aquaporins in each rat ocular tissue
      examined. In cornea, AQP1 is expressed approximately three-fold higher than AQP3
      and 2.5 fold higher than AQP5. However, the highest intraocular expressions of
      AQP3 and AQP5 are in the cornea. In the iris, expression levels of AQP1 are
      approximately 600-700 fold higher than AQP4 and AQP5. In the ciliary body, the
      expression levels of AQP1 are approximately ten-fold higher than AQP4, the only
      other aquaporin expressed. In the lens, the major water channel is AQP1 with
      detectable levels of AQP4 and AQP5 that are approximately 1000-fold lower than
      AQP1. In choroid, AQP1 is the only water channel expressed. In retin, AQP1 is
      expressed approximately six-fold higher than AQP4, the only other aquaporin
      expressed. However, the highest ocular expression of AQP4 is in retina. AQP2 is
      not detected in the eye. Finally, the possible physiological roles of aquaporins
      in maintaining and regulating the aqueous flow, and corneal and lens transparency
      are discussed.

PMID- 9176055
TI  - Distribution of lutein and zeaxanthin stereoisomers in the human retina.
AB  - The distribution of macular pigment stereoisomers in the human retina has been
      mapped and a pathway to account for the presence of the non-dietary carotenoid,
      meso-zeaxanthin, is proposed. Adult neural retinas were cut into three concentric
      areas centered on the fovea, and the extracted carotenoids were analysed and
      purified by high-performance liquid chromatography. The dicarbamate or dibenzoate
      derivatives of the collected zeaxanthin fractions for each tissue sample were
      further analysed by HPLC to determine their stereoisomer composition. Whole
      retinas from infant eyes were similarly analysed. The results show that, relative
      to zeaxanthin, the concentration of lutein in the adult neural retina increases
      with radial distance from the fovea while that of meso-zeaxanthin decreases.
      Infant retinas were found to have more lutein and less meso-zeaxanthin, relative
      to zeaxanthin, than adult retinas. Small quantities of (3S, 3'S)-zeaxanthin were
      also found in the adult retina, particularly in the macula. It is proposed that
      lutein and zeaxanthin are transported into an individual's retina in the same
      proportions found in his or her blood serum. Some of the lutein is then converted
      into meso-zeaxanthin, primarily in the macula, by a mechanism which is less
      developed in infants than adults.

PMID- 9176056
TI  - Analysis of small GTP-binding proteins of the lens by GTP overlay assay reveals
      the presence of unique GTP-binding proteins associated with fiber cells.
AB  - Low molecular weight GTP-binding proteins are molecular switches which are
      thought to play pivotal roles in cell growth, differentiation, cytoskeletal
      organization and vesicular trafficking. In this study, members of this family of
      proteins have been identified and characterized in the eye lens, for the first
      time. [alpha 33P]GTP blot overlay assays of monkey and human lens water soluble
      and membranous insoluble fractions revealed the presence of specific GTP-binding
      proteins in the range of 20-30 kDa (small GTPases) in both fractions, with much
      higher amounts in the membranous insoluble fraction. In the insoluble fraction,
      in addition to 20-30 kDa GTPases, there are three distinct GTP-binding proteins,
      ranging from 33-45 kDa. The small GTPases (20-30 kDa) were present throughout the
      lens in epithelium, cortex and nucleus, while the 33-45 kDa GTP-binding protein
      bands were exclusively associated with the cortex and nucleus (fiber cells).
      Analysis of lens fractions by two-dimensional electrophoresis,
      immunoprecipitation using monoclonal and sequence specific polyclonal antibodies
      and C3 exoenzyme mediated ADP-ribosylation demonstrated the presence of Ras, Rap,
      Rho, Rac, Rab and several other small GTPases. The 33-45 kDa GTP-binding proteins
      that are associated with lens fiber cells appear to be distinct from the small
      GTPases and from heterotrimeric GTPases, and were not detected in brain or heart
      tissue. The presence of different complements of GTP-binding proteins in lens
      fibers and epithelial, cells suggests their involvement in important regulatory
      functions, possibly related to cell growth, differentiation and organization of
      the cytoskeleton.

PMID- 9176057
TI  - Anti-beta-crystallin antibodies (mouse) or sera from humans with age-related
      cataract are cytotoxic for lens epithelial cells in culture.
AB  - Circulating autoantibodies against lens antigens are prevalent in patients with
      age-related cataract (ARC), but their pathogenic significance is unknown. We
      hypothesized that these autoantibodies are cytotoxic for lens epithelial cells
      (LECs). To test this hypothesis. We incubated LECs with mouse polyclonal or
      monoclonal antibodies against beta-crystallin (anti-beta) in the presence or
      absence of guinea pig complement. We found that anti-beta in the presence of the
      complement bound to and killed mouse LECs (MLECs) and human LECs (HLECs). Sera
      obtained from patients with ARC also were cytotoxic to both HLECs and MLECs in
      culture. Heat-inactivated human sera were not cytotoxic to LECs in the absence of
      the complement, but were cytotoxic to both HLECs and MLECs in the presence of
      additional complement. These results support the hypothesis that autoantibodies
      against lens antigens are cytotoxic to LECs, and that cell death may involve
      complement-mediated pathways.

PMID- 9176058
TI  - Basic fibroblast growth factor treatment delays age-related photoreceptor
      degeneration in Fischer 344 rats.
AB  - This study was undertaken to investigate the potential of basic fibroblast growth
      factor (bFGF) to delay photoreceptor cell loss in retinas of Fischer 344 rats
      which exhibit an age-related peripheral retinopathy. Eight male 16-month-old
      Fischer 344 rats were injected intravitreally with 2.0 micrograms bFGF in the
      right eye, while the vehicle was injected into the left eye and all rats were
      killed at two months post-injection. Eight other Fischer rats were injected with
      either bFGF or vehicle at 16 and again at 18 months, then killed two months
      later. After enucleation, eyes were processed for light and electron microscopic
      and morphometric analyses. The distance from the ora serrata to the point where
      the outer nuclear layer (ONL) in the superior retina was two cells in thickness,
      called the die-back zone, that represents the extent of the peripheral
      retinopathy, was compared in bFGF- and vehicle-injected Fischer rats. These
      measurements revealed that the die-back zone in retinas of eyes injected twice
      with bFGF was significantly reduced (P < 0.01) when compared to this zone in
      retinas of age-matched rats that received vehicle injections. However, there was
      no significant difference (P > 0.05) in this degeneration zone in retinas of 18
      month-old rats that received a single-bFGF injection when compared to retinas of
      respective vehicle-injected rats. In addition, the ONL at 2 and 3 mm from the ora
      serrata in the superior retina of bFGF-injected 20-month-old Fischer rats was
      significantly thicker than corresponding regions in retinas of vehicle-control
      rats. Furthermore, the photoreceptor cells in the superior retina of 20-month-old
      rats which received two injections of bFGF had normal-appearing inner and outer
      segments, while the few photoreceptors had short inner and outer segments in
      vehicle-injected retinas of Fisher rats. These findings reveal that injections of
      bFGF into eyes of Fischer 344 rats significantly delays the progress of
      photoreceptor cell degeneration suggesting that exogenous bFGF may act as a
      survival-promoting factor in these aged retinas.

PMID- 9176059
TI  - Protein kinase C activation by serotonin potentiates agonist-induced stimulation
      of cAMP production in cultured rat retinal pigment epithelial cells.
AB  - Serotonin stimulates inositol phosphate production and intracellular calcium
      mobilization in cultured rat retinal pigment epithelial (RPE) cells through
      interaction with 5-HT2A receptors, but decreases cAMP production in cultured
      human RPE cells via 5-HT1A receptors. Studies were therefore undertaken to
      investigate the effect of serotonin on the cAMP system in rat RPE cells. Exposure
      of cultured rat RPE cells to serotonin (100 microM) for 10 minutes had no effect
      on the basal levels of cAMP. However, a 5 minute preincubation with serotonin
      potentiated the production of cAMP induced by a 5 minute exposure to forskolin (5
      microM), isoproterenol (1 microM) and 5'-[N-ethylcarboxamido]-adenosine (10
      microM) by 133.0%, 296.8% and 651.9%, respectively. This effect of serotonin was
      dose-dependent on forskolin and 5'-[N-ethylcarboxamido]-adenosine with half
      maximal effects close to those reported for its action on inositol phosphates
      production. The antagonists ketanserin, methysergide and spiperone attenuated the
      action of serotonin, while yohimbine and spiroxatrine were ineffectual, thus
      indicating that the potentiating effect was through the 5-HT1A receptor.
      Incubation of cultured rat RPE cells with bradykinin stimulates inositol
      phosphates production with half-maximal effect observed at 1 nM. Bradykinin also
      potentiates the action of forskolin, isoproterenol and 5'-[N-ethylcarboxamido]
      adenosine on cAMP production in a dose-dependent manner with little effect on
      basal levels. RPE cells exposed to serotonin (500 microM) or phorbol 12-13
      dibutyrate (1 microM) for 30 minutes showed translocation of protein kinase C to
      the membrane from the cytosol, with 53.3% and 29.4% increases in membrane
      activity, respectively. Forskolin- and 5'-[N-ethylcarboxamido]-adenosine-induced
      cAMP production was potentiated by phorbol 12-13 dibutyrate (1 microM) treatment.
      The effect of both serotonin and phorbol 12-13 dibutyrate on forskolin-induced
      cAMP production was attenuated by pretreatment of cell cultures with the protein
      kinase C antagonists staurosporin and calphostin C at 1 microM. Thus, the
      production of cAMP in cultured rat RPE cells is potentiated by 5-HT2A receptors
      through activation of protein kinase C. This effect is, however, not specific
      since bradykinin, which stimulates inositol phosphates turnover, also potentiates
      stimulated cAMP production.

PMID- 9176060
TI  - ZO-1 reorganization and myofibroblast transformation of corneal endothelial cells
      after freeze injury in the cat.
AB  - Corneal endothelial wound healing following scrape injury in the rabbit and cat
      is characterized by cell spreading and maintenance of a normal endothelial
      phenotype consisting of apically-localized, circumferential microfilament bands
      and cell border-associated ZO-1, a tight junction protein and marker for
      endothelial differentiation. In contrast, after freeze injury in the rat and
      rabbit endothelial cells develop basally organized microfilament bundles (stress
      fibers), and appear to proliferate and form a multilayered zone at the wound
      margin. The purpose of the present study was to determine if similar phenotypic
      changes are observed after freeze injury in the cat corneal endothelium, which
      like human, normally has limited growth potential. In addition, changes in ZO-1
      and alpha-smooth muscle actin (a marker for myofibroblast transformation)
      distribution were evaluated for the first time following freeze injury. In vivo
      endothelial healing of standard 3 mm diameter freeze injury was evaluated at 4
      hr, 12 hr, 24 hr, 48 hr, 3 days and 5 days after injury in 22 cat eyes. Corneas
      were stained with phalloidin, propidium iodide, and anti-ZO-1, anti-alpha-smooth
      muscle-specific actin or anti-fibronectin antibodies. Protein organization was
      then evaluated using immunofluorescence and laser scanning confocal microscopy.
      Beginning at 12 hr after injury, endothelial cells appeared to extend and
      elongate over the wound area. By 48 hr after injury, migrating endothelial cells
      formed a multilayered activated zone (AZ) at the wound margin. Endothelial cells
      immediately adjacent to the AZ maintained a normal circumferential organization
      of f-actin colocalized with cell border-associated anti-ZO-1 staining at all time
      points observed. However, within the AZ there was an abrupt increase in
      phalloidin staining and development of prominent microfilament bundles (stress
      fibers), as well as a loss of normal anti-ZO-1 staining. The AZ also stained
      positively for anti-alpha-smooth muscle actin and anti-fibronectin antibodies.
      Changes in the distribution of ZO-1 were observed as early as 4 hr after injury,
      and appeared to precede f-actin reorganization. These data indicate that
      endothelial healing after freeze injury in the cat involves a loss of normal
      endothelial differentiation and cell connectivity, and transformation to a
      myofibroblastic phenotype.

PMID- 9176061
TI  - The 5' flanking regions of IRBP and arrestin have promoter activity in primary
      embryonic chicken retina cell cultures.
AB  - Primary cultures of embryonic chicken cells from various tissues were transiently
      transfected with plasmid vectors containing reporter genes linked to a 1.8 kb
      fragment of the mouse interphotoreceptor retinoid-binding protein (IRBP) 5'
      flanking region, a 1.5 kb fragment of the mouse arrestin 5' flanking region, or a
      3.4 kb sequence of the bovine arrestin 5' flanking region. Promoter activity was
      evident in retina-derived cells, but not in fibroblasts or cells from whole
      brain. Transfection response also varied with transfection method, plasmid DNA
      concentration, post-transfection incubation time, and cell density. The data
      suggest that the primary embryonic chicken retinal cell culture system is a
      useful tool in studying photoreceptor-specific gene regulation.

PMID- 9176062
TI  - Squalene is localized to the plasma membrane in bovine retinal rod outer
      segments.

PMID- 9176063
TI  - Identification of N-acetylaspartate in the lens of the vertebrate eye: a new
      model for the investigation of the function of N-acetylated amino acids in
      vertebrates.

PMID- 9176064
TI  - The transcription factor, Kid-1, is highly expressed in both eye and kidney of
      the mouse.

PMID- 9176065
TI  - The release of amino acids from ischemic retina.

PMID- 9176066
TI  - Regulation of intestinal non-haem iron absorption.

PMID- 9176067
TI  - Autoimmune cholangitis.

PMID- 9176068
TI  - Tumour necrosis factor and Crohn's disease.

PMID- 9176069
TI  - Effect of intraduodenal fat on lower oesophageal sphincter function and gastro
      oesophageal reflux.
AB  - BACKGROUND AND AIMS: Fatty foods are commonly reported to aggravate gastro
      oesophageal reflux symptoms. In this study the hypothesis that fat provokes
      reflux by stimulating transient lower oesophageal sphincter relaxations via small
      intestinal receptors was investigated. METHODS: In 12 healthy volunteers and 11
      patients with reflux oesophagitis, oesophageal motility and pH were measured over
      30 minute periods during which saline or fat (10% Intralipid) were infused in
      random order into the duodenum. The infusion periods were separated by a 30
      minute washout. The stomach was loaded with 200 ml 10% dextrose, maintained by an
      intragastric infusion. RESULTS: Fat decreased basal LOS pressure from 16.9 (SEM
      2.1) to 12.4 (SEM 1.5) mm Hg in normal subjects but had no effect in patients
      with oesophagitis (18.8 (SEM 4.3) v 18.2 (SEM 3.0) mm Hg). During saline
      infusion, the rates of transient lower oesophageal sphincter relaxation and
      reflux episodes were greater in patients (4.5 (interquartile range 2-11)/30 min
      and 5 (2-14)/30 min respectively) than in controls (3 (2-4)/30 min and 3 (2
      3.5)/30 min respectively). Fat increased the rate of reflux episodes in the
      reflux patients to 6.5 (3-25)/30 min. This effect was due to an increase in the
      incidence of reflux during transient LOS relaxations (65% v 91%), the rate of
      transient relaxations remaining unchanged. CONCLUSIONS: Instillation of fat
      directly into the duodenum aggravates reflux in patients with reflux disease, by
      increasing the proportion of transient LOS relaxations accompanied by reflux.

PMID- 9176070
TI  - Comparison of serum, salivary, and rapid whole blood diagnostic tests for
      Helicobacter pylori and their validation against endoscopy based tests.
AB  - BACKGROUND: A rapid, reliable, and accurate test for the diagnosis of infection
      with Helicobacter pylori is needed for screening dyspeptic patients before
      referral for endoscopy. AIM: To compare a new rapid whole blood test (Helisal
      rapid blood, Cortecs), two serum enzyme linked immunosorbent assays (ELISAs;
      Helico-G, Shield and Helisal serum, Cortecs), and a salivary assay (Helisal
      saliva, Cortecs), with slide biopsy urease, 13C-urea breath test, and histology.
      METHODS: Three hundred and three consecutive dyspeptic patients attending for
      gastroscopy underwent two antral biopsies for histology, and one for rapid slide
      biopsy urease test for assessment of H pylori status. Blood and saliva were also
      collected. One hundred of the patients also underwent a 13C-urea breath test.
      Gold standard positives were defined as those with at least two positive tests
      among slide urease, breath test, or histology, and gold standard negatives as
      those with all these (or two when the breath test was not done) negative.
      RESULTS: Of 300 patients (median age 63, range 28-89) eligible for analysis, 137
      (46%) were gold standard positives, of which Helisal rapid blood identified 116,
      Helico-G 129, Helisal serum 130, and Helisal saliva 120; 137 (46%) were gold
      standard negatives of which the number falsely identified as positive was 30 by
      Helisal rapid blood, 45 by Helico-G, 41 by Helisal serum, and 41 by Helisal
      saliva. Sensitivities and specificities were: for the whole blood test 85% and
      78% respectively; for Helico-G 94% and 67%, for Helisal serum 95% and 70%, and
      for Helisal saliva 84% and 70%. CONCLUSIONS: If endoscopy had been undertaken
      only on patients with positive tests two of 16 duodenal ulcers would have been
      missed if the Helisal rapid blood test was used, and one if any of the ELISA
      tests were used. None of the blood tests would have missed any of six gastric
      ulcers, but the salivary test would have missed one.

PMID- 9176071
TI  - A citric acid solution is an optimal test drink in the 13C-urea breath test for
      the diagnosis of Helicobacter pylori infection.
AB  - BACKGROUND: The 13C-urea breath test (13C-UBT) is a simple, non-invasive and
      reliable test for the diagnosis of Helicobacter pylori infection. The duration of
      the test, the timing of breath sampling, and the accuracy of the method vary
      according to the test meal used. AIM: To identify the optimal test meal or drink
      for rapid and accurate performance of the 13C-UBT for the detection of H pylori
      infection. PATIENTS: Eighty patients with dyspeptic symptoms were included. Of
      these, 48 patients had a positive H pylori status and 32 a negative one according
      to the results of the rapid urease test, histological examination, and culture.
      METHODS: A 13C-UBT was performed after an overnight fast, on three consecutive
      days. On each study day a different test meal or drink was given (0.1 N citric
      acid solution, a standard semiliquid meal, or a semiliquid fatty meal) 10 minutes
      before giving 75 mg 13C-urea. Breath samples were collected at 0, 15, 30, 45, and
      60 minutes, and analysed by isotype ratio mass spectrometry. Results were
      expressed as delta (delta) and considered as positive for H pylori if the highest
      delta (peak) was greater than 4.0. RESULTS: The delta peak obtained with the
      citric acid drink in H pylori positive subjects (24.1 (SEM 1.5)) was
      significantly higher than that obtained with any of the semiliquid meals (13.3
      (SEM 1.1) and 17.1 (SEM 1.0) respectively, p < 0.001). Furthermore, this delta
      peak was obtained earlier with the citric acid drink (30 (SEM 2) minutes) than
      with the other two meals tests (53 (SEM 2) min and 45 (SEM 2) min, p < 0.001).
      The sensitivity of the 13C-UBT for the diagnosis of H pylori infection was 96
      100% with all three test meals. This high sensitivity was, however, obtained from
      15 minutes by giving citric acid as the test drink, from 45 minutes by giving a
      semiliquid fatty meal, and at 60 minutes by giving the semiliquid standard meal.
      The specificity was 100% for all test meals. Citric acid is inexpensive and
      palatable to patients. CONCLUSIONS: The 13C-UBT procedure with citric acid as the
      test drink is superior to the previously proposed semiliquid test meals in terms
      of 13CO2 recovery, time requirement, and cost. In routine clinical sampling,
      collection at times 0 and 30 minutes seems to be optimal and gives a high
      diagnostic accuracy.

PMID- 9176072
TI  - Mucosal expression and luminal release of epidermal and transforming growth
      factors in patients with duodenal ulcer before and after eradication of
      Helicobacter pylori.
AB  - BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor-alpha
      (TGF alpha) are potent gastric acid inhibitors and stimuli of mucosal growth and
      protection but their involvement in Helicobacter pylori associated duodenal ulcer
      has been little examined. AIM: To assess gastric acid secretion, plasma gastrin
      concentrations, mucosal content of EGF and TGF alpha, and mucosal expression of
      these peptides and their receptor (EGFr) as well as salivary and gastric luminal
      release of EGF under basal conditions and after pentagastrin stimulation in 10
      healthy subjects and in 25 H pylori positive patients with duodenal ulcer before
      and after two weeks of triple anti-H pylori therapy and four weeks after the
      termination of this therapy. RESULTS: Pentagastrin stimulation caused a
      significant increase in salivary and gastric release of EGF both in healthy
      controls and patients with duodenal ulcers but in the patients, the eradication
      of H pylori resulted in several fold higher gastric luminal (but not salivary)
      EGF release than before the anti-H pylori therapy. Mucosal contents of
      immunoreactive EGF and TGF alpha and mucosal expression of EGF, TGF alpha, and
      EGFr in H pylori positive patients with duodenal ulcer were significantly higher
      than those in healthy H pylori negative controls and this increase persisted
      after eradication of H pylori. Basal plasma gastrin was significantly reduced
      after two weeks of triple therapy and four weeks after the H pylori eradication
      all ulcers were completely healed. CONCLUSIONS: (1) H pylori infection in
      patients with duodenal ulcer was accompanied by enhanced plasma gastrin and
      increased mucosal content and expression of TGF alpha, EGF, and EGFr; (2) H
      pylori eradication resulted in ulcer healing, reduction in plasma gastrin, and
      enhancement of gastric (but not salivary) luminal release of EGF, particularly
      after pentagastrin stimulation; and (3) enhanced mucosal content and expression
      of TGF alpha, EGF, and EGFr and increased luminal release of EGF may contribute
      to ulcer healing after eradication of H pylori.

PMID- 9176073
TI  - Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve
      corticosteroid dependent chronic active Crohn's disease.
AB  - BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an
      increased production of proinflammatory cytokines, in particular tumour necrosis
      factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce
      a host of cellular effector events resulting in perpetuation of the inflammatory
      process. In vivo studies with anti-TNF alpha antibody treatment have led to
      impressive clinical results. AIMS: To investigate whether treatment with the TNF
      alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid
      dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease
      patients received oxpentifylline 400 mg four times a day in a four week open
      label study. RESULTS: Blockade of TNF alpha production in 16 patients with
      corticosteroid dependent Crohn's disease did not improve the clinical disease
      activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic
      degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory
      parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor
      oxpentifylline does not improve inflammation in Crohn's disease. This finding
      suggests that there may be more key mediators than only TNF alpha in the
      inflammatory process in Crohn's disease.

PMID- 9176074
TI  - In vitro effects of oxpentifylline on inflammatory cytokine release in patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF
      alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of
      intestinal inflammation in inflammatory bowel disease. AIM: To investigate the in
      vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase
      inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear
      cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with
      Crohn's disease and patients with ulcerative colitis. METHODS: PBMCs and mucosal
      biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up
      to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8
      determined by enzyme linked immunosorbent assays (ELISAs). RESULTS: PTX inhibited
      the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease
      and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa
      from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about
      50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in
      cultures from controls, patients with Crohn's disease, and those with ulcerative
      colitis. The concentrations of IL-6 and IL-8 were not significantly modified in
      PBMCs, but IL-6 increased slightly in organ culture supernatants. CONCLUSIONS:
      PTX or more potent related compounds may represent a new family of cytokine
      inhibitors, potentially interesting for treatment of inflammatory bowel disease.

PMID- 9176075
TI  - Pancreatic autoantibodies in Crohn's disease: a family study.
AB  - BACKGROUND: Pancreatic antibodies occur in about one third of patients with
      Crohn's disease. AIMS: To evaluate the relevance of pancreatic antibodies as a
      genetic marker in patients with Crohn's disease and their first degree family
      members and spouses. To characterise further pancreatic antibodies by assessment
      of IgG subclasses. METHODS: Six hundred and fifty serum samples were tested for
      pancreatic antibodies by immunofluorescence on sections of human pancreas.
      Incidence of pancreatic antibodies and their subtypes were studied on 212 serum
      samples from patients with Crohn's disease. In the familial study, 72 patients
      with Crohn's disease and 196 first degree family members and 26 patients with
      ulcerative colitis and 90 first degree family members were included. Ten healthy
      families served as controls. RESULTS: Pancreatic antibodies were found in 58
      (27%) of the patients with Crohn's disease and in none of the controls. Thirty
      patients had pancreatic antibodies of subtype I characterised by a drop-like
      fluorescence in the pancreatic acini, 28 patients had subtype II with a fine
      speckled staining in the acinar cells. Pancreatic antibodies of subtype I were
      both IgG1 and IgG2 antibodies by contrast with subtype II which were mainly of
      IgG1 subclass. Only five of 196 first degree relatives of patients with Crohn's
      disease had pancreatic antibodies. Four of these people had anamnestic data
      compatible with inflammatory bowel disease. Further investigations showed Crohn's
      disease in two of these people. In families with more than one member positive
      for pancreatic antibodies, pancreatic antibodies were of the same subtype in all
      cases. CONCLUSIONS: Pancreatic antibodies are a specific marker for Crohn's
      disease. Two subgroups of pancreatic antibodies can be distinguished by their
      pattern and immunoglobulin subclasses. Pancreatic antibodies rarely occur in
      family members of patients with Crohn's disease. These family members may also
      have Crohn's disease.

PMID- 9176076
TI  - Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a
      randomised, placebo controlled trial.
AB  - BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis
      in animals and humans, and the mucosal metabolism of these compounds is decreased
      in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in
      ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative
      colitis were entered into a six week, double-blind, placebo controlled trial of
      rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA
      in an open-label extension trial. RESULTS: Of the 91 patients completing the
      trial, more patients in the SCFA treated than in the placebo treated group
      improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but
      statistically non-significant, reductions in every component of their clinical
      and histological activity scores. In patients with a relatively short current
      episode of colitis (< 6 months, n = 42), more responded to SCFA than to placebo
      (48% v 18%, p = 0.03). These patients also had larger, but statistically non
      significant, decreases in their clinical activity index (p = 0.08 v placebo).
      Every patient who improved used at least five of six of the prescribed rectal
      SCFA irrigations, whereas only 37% who did not improve were as compliant. In the
      open-label extension trial, 65% improved on SCFA; these patients also had
      significant reductions (p < 0.02) in their clinical and histological activity
      scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this
      controlled trial, the results suggest efficacy in subsets of patients with distal
      ulcerative colitis including those with short active episodes. Prolonged contact
      with rectal mucosa seems to be necessary for therapeutic benefit.

PMID- 9176077
TI  - Down's syndrome is strongly associated with coeliac disease.
AB  - BACKGROUND: There is evidence of an increased prevalence of coeliac disease in
      Down's syndrome. AIMS: To investigate the association, patients with Down's
      syndrome and matched controls were examined. METHODS: Fifty nine patients with
      Down's syndrome residing in government institutions in the Hunter region of New
      South Wales were studied. Four were excluded (terminally ill = 1, uncooperative =
      3). Each of 55 patients was matched for age, sex, and residence with a control
      patient. Patients with both positive IgA and IgG antigliadin antibodies were
      considered for endoscopical duodenal biopsy. RESULTS: Twenty one patients and two
      controls had raised IgA and IgG antibodies (chi 2 = 19.4; p < 0.001). Tissue was
      obtained in 18 patients. Two had characteristic flat, five pronounced lymphocytic
      infiltration not diagnostic of coeliac disease, two giardiasis, and eight were
      normal. In one the tissue was not suitable for analysis. There were few
      differences between the subgroups in their anthropomorphic, biochemical, or
      haematological findings. CONCLUSIONS: The prevalence of coeliac disease in these
      51 patients with Down's syndrome is at least two (3.9%; 95% confidence interval
      (95% CI) 0%-9.2%) and could be as many as seven (13.7%; 95% CI 4.3%-23.2%). In
      this community the prevalence of coeliac disease in Down's syndrome is increased
      more than 100-fold (x135-473).

PMID- 9176078
TI  - Increasing the intestinal resistance of rats to the invasive pathogen Salmonella
      enteritidis: additive effects of dietary lactulose and calcium.
AB  - BACKGROUND AND AIMS: Lactulose fermentation by the intestinal microflora
      acidifies the gut contents, resulting in an increased resistance to colonisation
      by acid sensitive pathogens. The extent of fermentation should be controlled to
      prevent acid induced epithelial cell damage. Considering the buffering capacity
      of calcium phosphate and its intestinal cytoprotective effects, whether
      supplemental calcium phosphate adds to the increased resistance to intestinal
      infections by lactulose fermentations was studied. METHODS: In a strictly
      controlled experiment, rats were fed a purified low calcium control diet, a low
      calcium/lactulose diet, or a high calcium/lactulose diet, and subsequently
      infected orally with Salmonella enteritidis. RESULTS: Lactulose fermentation
      lowered the pH and increased the lactic acid concentration of the intestinal
      contents, which significantly reduced excretion of this pathogen in faeces; thus
      it improved the resistance to colonisation. This agreed with the high sensitivity
      of S enteritidis to lactic acid (main metabolite of lactulose fermentation) in
      vitro. Calcium phosphate decreased translocation of S enteritidis to the systemic
      circulation, an effect independent of lactulose. The unfavourable increased
      cytotoxicity of faecal water caused by lactulose fermentation was more than
      counteracted by supplemental calcium phosphate. Moreover, calcium phosphate
      stimulated lactulose fermentation, as judged by the reduced lactulose excretion
      in faeces and increased lactic acid, ammonia, and faecal nitrogen excretion.
      CONCLUSION: Extra calcium phosphate added to a lactulose diet improves the
      resistance to colonisation and translocation of S enteritidis. This is probably
      mediated by a calcium induced stimulation of lactulose fermentation by the
      intestinal microflora and reversion of the lactulose mediated increased luminal
      cytotoxicity, which reduces damage inflicted on the intestinal mucosa.

PMID- 9176079
TI  - Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in
      vivo.
AB  - BACKGROUND: Shigella enterotoxin 1 is a novel enterotoxin elaborated by Shigella
      flexneri 2a that causes fluid accumulation in rabbit ileal loops and a rise in
      short circuit current in Ussing chambers. AIMS: To gain insights into the
      mechanism of action of shigella enterotoxin 1. METHODS: Supernatants from
      genetically engineered clones either overexpressing shigella enterotoxin 1 or
      producing deletion mutants of the toxin were tested in rabbit ileum both in vitro
      and in vivo. RESULTS: In rabbit ileum shigella enterotoxin 1 induced an
      irreversible rise in short circuit current that was not mediated by any of the
      recognised intracellular mediators of secretion. Deletion of 90% of the A subunit
      of the holotoxin ablated its enterotoxicity. In the in vivo perfusion model, the
      toxin induced a time dependent decrease in water absorption, whereas no changes
      were detected in the segment perfused with supernatants obtained from the
      deletion mutant. Finally, partially purified toxin induced a dose dependent
      increment in short circuit current that reached its plateau at a toxin
      concentration of 4 x 10(-6) M. CONCLUSIONS: Shigella enterotoxin 1 induces a time
      and dose dependent intestinal secretion in the rabbit animal model, suggesting
      that it may be responsible for the watery phase of Shigella flexneri 2a
      infection.

PMID- 9176080
TI  - Micrometastases: marker of metastatic potential or evidence of residual disease?
AB  - BACKGROUND: Micrometastases within bone marrow have been shown to indicate a poor
      prognosis in patients with epithelial tumours. However, the degree to which
      micrometastases represent true residual disease or cell shedding and metastatic
      potential, is unclear. AIM: To explore whether micrometastases represent residual
      disease, bone marrow taken from carefully staged patients before and after (> 6
      months) "curative" resection of a primary gastrointestinal cancer was studied
      prospectively. PATIENTS/METHODS: Seventy two consecutive patients were studied;
      the only exclusions were patients with known overt metastatic disease at the time
      of surgery. Micrometastatic cells were quantified per 10(5) marrow cells by flow
      cytometry after staining for contaminant cytokeratin-18 positive cells. RESULTS:
      Micrometastases were detected preoperatively in 22% (16/72) of all patients,
      comprising 11 (23%) of 48 with colorectal cancer, five (33%) of 15 with gastric
      adenocarcinoma and none (0%) of nine with oesophageal squamous cancer. Although
      fewer metastatic cells were detected in postoperative bone marrow, and clearance
      of marrow deposits was evident in most patients, the persistence of
      micrometastases in five of 16 patients after resection, without evidence of
      tumour recurrence, indicates a subset with true residual disease. Detection of
      micrometastases postoperatively (persistent or newly developed) was significantly
      associated with development of overt metastases during the subsequent 12-18
      months of follow up (nine of 19 patients) when compared with patients testing
      negative for micrometastases (eight of 53; p < 0.01). CONCLUSIONS: Preoperative
      detection of micrometastases may reflect either transient shedding of cells,
      metastatic potential or residual disease, but postoperative micrometastases
      indicate minimal residual disease. Identification of these patients is important
      because they may benefit from adjuvant therapy.

PMID- 9176081
TI  - Differential expression of oestrogen receptor and oestrogen inducible genes in
      gastric mucosa and cancer.
AB  - BACKGROUND: Evidence exists for a role for oestrogen in gastric cancer. The
      incidence of gastric cancer is much higher in men than in woman, and a similar
      sex difference is also seen in a rat experimental model of gastric cancer. AIMS:
      Evidence for a functional oestrogen receptor in normal gastric mucosa and cancer
      has been sought. METHODS: Oestrogen receptor and the oestrogen inducible genes
      pS2 and ERD5 were sought by northern blot analysis and in situ hybridisation and
      immunohistochemistry. Oestrogen receptor protein was studied by enzyme
      immunoassay. RESULTS: mRNA for oestrogen receptor was detected in cancer and
      normal gastric mucosa. Enzyme immunoassay for oestrogen receptor showed a mean of
      1.8 fmol/mg protein in cancer and 13.7 fmol/mg in paired normal mucosa. The
      oestrogen inducible genes pS2 and ERD5 were also detected in both cancer and
      normal mucosa, with expression localised to epithelium. Expression of pS2 was
      lower in cancer compared with normal mucosa, whereas ERD5 expression was higher
      in cancer. CONCLUSIONS: Significant amounts of oestrogen receptor were expressed
      in gastric mucosa with a lower amount in cancer. Oestrogen inducible genes were
      also expressed differentially but were not found to correlate closely with
      oestrogen receptor. Oestrogen receptor functionality remains to be demonstrated
      in the stomach.

PMID- 9176082
TI  - APC gene mutations and extraintestinal phenotype of familial adenomatous
      polyposis.
AB  - BACKGROUND: Familial adenomatous polyposis (FAP) is caused by germline mutation
      of the adenomatous polyposis coli (APC) gene on chromosome 5q. AIMS: This study
      assessed genotype-phenotype correlations for extraintestinal lesions in FAP.
      METHODS: Mutations of the APC gene were compared with the occurrence of seven
      extraintestinal manifestations in 475 FAP patients from 51 families. The
      frequency of manifestations was adjusted for different ages of patients using
      person years of exposure. In pedigrees without identified APC gene mutation,
      analysis of linkage to chromosome 5q and/or assessment of neoplasms for
      replication errors characteristic of mutation in mismatch repair genes were
      performed. RESULTS: FAP patients from the 42 families (82%) with identified
      mutations of the APC gene had more frequent expression of extraintestinal
      manifestations than affected individuals without identified mutations (risk ratio
      1.2-4.0; significant difference for cutaneous cysts). The presence of a cutaneous
      cyst or extraintestinal cancer significantly increased the likelihood of
      detection of a mutation in the APC gene (94% and 92% respectively; p < 0.05). In
      patients without identified APC gene mutation, linkage to the APC gene was found
      in one large family (lod = 5.1, theta 0.01), and replication error phenotype was
      absent in all 24 neoplasms from 16 members of these nine pedigrees. Expression of
      pigmented ocular fundus lesions was strongly associated with mutations in codons
      541-1309, but no other extraintestinal manifestations were related to mutation
      position. Multiplicity of extraintestinal manifestations was high with mutation
      in codons 1465, 1546, and 2621. CONCLUSIONS: Patients with the colorectal
      phenotype of FAP but no extraintestinal manifestations may have non-truncating
      mutations of the APC gene or mutation in a gene other than APC or mismatch repair
      genes. The site of APC gene mutation is associated with pigmented ocular fundus
      lesions (codons 542-1309) and predisposition to multiplicity of extraintestinal
      manifestations (codons 1465, 1546, and 2621).

PMID- 9176084
TI  - Combined treatment with C1 esterase inhibitor and antithrombin III improves
      survival in severe acute experimental pancreatitis.
AB  - BACKGROUND: Patients with severe acute pancreatitis die of complications closely
      related to the systemic activation of protease cascades. AIM: To examine the
      effects of human C1 esterase inhibitor (C1 INH) and antithrombin III (AT III) on
      two experimental models of acute pancreatitis. METHODS: Oedematous pancreatitis
      was induced by continuous intravenous infusion of caerulein and haemorrhagic
      pancreatitis by retrograde injection of sodium taurocholate into the
      biliopancreatic duct. C1 INH and AT III were given intravenously, either before
      or after the induction of pancreatitis. Treatment with C1 INH and AT III had no
      beneficial effect on oedematous pancreatitis. On the other hand, combined C1 INH
      and AT III therapy improved the survival in haemorrhagic pancreatitis compared
      with treatment with human serum albumin. This reduction in mortality was found
      regardless of whether the treatment was given prophylactically or
      therapeutically. CONCLUSIONS: Treatment with C1 INH and AT III represents a
      promising therapeutic concept for patients with severe haemorrhagic pancreatitis.

PMID- 9176083
TI  - Influence of changes in pancreatic tissue morphology and capillary blood flow on
      antibiotic tissue concentrations in the pancreas during the progression of acute
      pancreatitis.
AB  - BACKGROUND: The ability of an antibiotic to reach bactericidal concentrations in
      tissue depends on numerous factors including tissue composition and regional
      perfusion. Although necrotising pancreatitis is characterised by progression of
      pancreatic necrosis over at least 96 hours and microcirculatory alterations, the
      impact of these changes on the concentration of antibiotics in the pancreas has
      not yet been investigated. AIM: To determine and compare pancreatic tissue
      concentrations of imipenem and cefotaxime at different stages of acute
      necrotising pancreatitis in an animal model that has been shown to mimic closely
      the pathomorphological and bacteriological features of severe human pancreatitis.
      METHOD: Acute necrotising pancreatitis was induced in rats by a standardised
      intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours
      (n = 16) and 48 hours (n = 16) after induction of pancreatitis, the animals were
      randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen
      minutes after injection of the antibiotic, the animals were killed. Blood and the
      head of the pancreas were collected for determining imipenem or cefotaxime in
      serum and tissue; the splenic portion of the pancreas was prepared for
      histological examination. In an additional set of identically treated animals,
      pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy
      before induction of acute necrotising pancreatitis and at the time of antibiotic
      therapy. RESULTS: Imipenem accumulates in the pancreas in the initial phase of
      acute necrotising pancreatitis characterised by pronounced oedema and decreased
      PCBF, and tends to decrease with resolution of the oedema and the progression of
      acinar cell necrosis in the later course of the disease. Concentrations of
      cefotaxime are low in oedematous pancreatic tissue early after induction of acute
      necrotising pancreatitis and increase with the resolution of oedema and
      normalisation of PCBF. CONCLUSIONS: Concentrations of antibiotics in the pancreas
      vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue
      morphology and capillary blood flow. This suggests that antibiotic tissue
      concentrations may not be consistent from one agent to another and that efficacy
      of antibiotics in acute pancreatitis cannot be estimated solely on the basis of
      their pharmacological and microbiological properties.

PMID- 9176085
TI  - Effect of chronic endogenous hypergastrinaemia on pancreatic growth and
      carcinogenesis in the hamster.
AB  - BACKGROUND: To examine the effect of gastrin on spontaneous and induced
      pancreatic carcinogenesis in the hamster. METHODS AND RESULTS: Two sets of
      experiments were carried out, one involving long term hypergastrinaemia and one
      involving cancer induction during hypergastrinaemia. The effect of
      hypergastrinaemia accomplished by gastric fundectomy was studied for eight
      months. Neither fundectomised hamsters nor sham operated controls developed
      premalignant or malignant pancreatic lesions. In the fundectomy group, the mean
      pancreatic weight, total protein content, and DNA content was increased by 28%,
      25%, and 25% respectively. No such increases were found in fundectomised animals
      receiving a cholecystokinin-B receptor antagonist during the last 24 days of the
      experiment. In the cancer induction study, the effect of fundectomy on N
      nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for
      three months. There were no significant differences in the incidence or [3H]
      thymidine labelling index of focal pancreatic lesions between fundectomised and
      sham operated control animals. CONCLUSIONS: Fundectomy with chronic
      hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N
      nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster.
      The increases in growth were inhibited by a cholecystokinin-B receptor
      antagonist, indicating that the trophic effect of fundectomy is mediated by
      gastrin.

PMID- 9176086
TI  - Topical glyceryl trinitrate relaxes the sphincter of Oddi.
AB  - BACKGROUND/AIM: Nitric oxide (NO) may be involved in non-adrenergic non
      cholinergic (NANC) inhibitory innervation of the sphincter of Oddi (SO). The
      effects of topical application of glyceryl trinitrate (GTN), a NO donor, upon SO
      motility were examined. METHODS: Nineteen patients undergoing routine SO
      manometry for investigation of abdominal pain were studied. After routine
      recording of SO motility, they were randomised into three groups to receive 10 ml
      of normal saline, 5 mg GTN (0.5 mg/ml) or 10 mg (1 mg/ml) GTN. Drug solutions
      were infused topically onto papilla via the manometry catheter and recordings
      were continued for a further 5 minutes. RESULTS: There was no significant change
      in SO motor variables following application of normal saline. GTN reduced SO
      tonic and phasic contractions. In four patients, there was complete abolition of
      all phasic contraction. CONCLUSIONS: Local application of GTN inhibits SO
      motility. This may have application for diagnostic and therapeutic biliary
      endoscopy.

PMID- 9176087
TI  - Acquired C3 deficiency in patients with alcoholic cirrhosis predisposes to
      infection and increased mortality.
AB  - BACKGROUND: Acquired deficiencies of certain complement proteins and impaired
      opsonisation activity have been implicated in the pathogenesis of the increased
      susceptibility to infections of patients with alcoholic cirrhosis. METHODS: Serum
      concentrations of C3 and C4, plasma concentrations of C3bc, C9, and the terminal
      C5b-9 complement complex (TCC), and haemolytic complement activity (classic and
      alternative pathway) of serum, and serum opsonic activity were determined in 46
      patients with compensated alcoholic cirrhosis, 31 who were decompensated, and in
      15 healthy subjects. After 19 months (median) the investigated variables were
      analysed for their use in prognosis of recurrent infections and survival.
      RESULTS: C3 and C4 concentrations and the haemolytic complement activity of the
      alternative pathway were decreased in decompensated cirrhotic patients compared
      with controls (p < 0.01). Univariate analysis (log rank test) showed that low
      concentrations (< or = lower quartile) of C3 (p < 0.001) and C3bc (p < 0.05),
      haemolytic complement activity of the alternative pathway (p < 0.01) and classic
      pathway (p < 0.05), and decompensated cirrhosis (p < 0.001) were associated with
      an increased risk of infection and increased mortality. Multivariate (Cox)
      analysis showed that low C3 concentrations and decompensation of cirrhosis were
      significant predictors of infections and mortality (p < 0.02). CONCLUSIONS: Low
      serum C3 concentrations and decreased haemolytic complement function predisposes
      to infection and increased mortality in patients with alcoholic cirrhosis.

PMID- 9176088
TI  - Granulomatous gastritis in Wegener's disease: differentiation from Crohn's
      disease supported by a positive test for antineutrophil antibodies.
AB  - BACKGROUND: This report concerns the gastric manifestation of Wegener's
      granulomatosis in a 44 year old white female patient who initially presented with
      abdominal pain, vomiting, and iridocyclitis. FINDINGS: The clinical findings and
      the histopathological proof of granulomatous gastritis in the absence of
      necrotising vasculitis were initially considered to be indicative of a diagnosis
      of Crohn's disease showing isolated gastric involvement. A five month course of
      steroids resulted in temporary relief; thereafter the patient developed severe
      rhinitis with mucosal ulcerations. At this point biopsy of nasal mucosa disclosed
      the classic histopathological signs of Wegener's granulomatosis. A positive test
      for antineutrophil cytoplasmic antibodies (ANCAs) with a cytoplasmic pattern (c
      ANCA) and antigenic specificity for proteinase 3 (PR-3) were found. The patient
      is in complete remission one year after diagnosis and treatment with steroids and
      cyclophosphamide. CONCLUSIONS: Wegener's granulomatosis can also involve the
      gastrointestinal tract. Granulomatous inflammation of the stomach, although a
      rare finding and non-specific, should include Wegener's disease in the
      differential diagnosis. The histological proof of necrotising vasculitis is
      dependent on the depth of the biopsy and therefore can be easily missed.
      Differential diagnosis can be clarified by ANCA testing.

PMID- 9176089
TI  - Video education and evidence in endoscopy.

PMID- 9176090
TI  - Micrometastases: are they clinically significant disease?

PMID- 9176091
TI  - Antibody 'markers' in Crohn's disease: opportunity or overstatement?

PMID- 9176092
TI  - Oxpentifylline, tumour necrosis factor-alpha and Crohn's disease.

PMID- 9176093
TI  - Soluble TNF receptors as prognostic factors for mortality.

PMID- 9176094
TI  - Helicobacter pylori and ulcer healing.

PMID- 9176095
TI  - Endoscopic papillectomy.

PMID- 9176096
TI  - T-cell cytokines may control the balance of functionally distinct macrophage
      populations.
AB  - As monocytes differentiate into mature macrophages, subsets emerge that exhibit
      stimulatory, suppressive or phagocytic potential. These functionally distinct
      subsets can be discriminated using monoclonal antibodies RFD1 and RFD7. As
      examples of all these subsets have been repeatedly identified within the
      macrophage pool in a variety of organs the overall functional capacity of this
      pool will depend on the relative balance of these subpopulations. This study
      investigates whether this balance present in mature macrophage populations can be
      regulated by the local influence of T-cell-derived cytokines. The dose-dependent
      effect of cytokines interferon-gamma (IFN-gamma), interleukins (IL) IL-2, IL-4
      and IL-10 on the phenotype and function of monocyte-derived macrophages was
      determined. Subsets of mature cells were quantified by identifying RFD1- RFD7-
      stimulatory cells (D1+); RFD1- RFD7+ phagocytes (D7+) and RFD1+ RFD7+ suppressive
      cells (D1 D7+). IFN-gamma and IL-4 increased the relative proportions of D1+
      stimulatory cells and upregulated HLA-DR expression. IFN-gamma also increased the
      capacity of the mature macrophage pool to stimulate T-cell proliferation. IL-10
      reduced the proportions of D1+ stimulatory cells while promoting the
      differentiation of D7+ phagocytes and D1/D7+ suppressive cells. IL-10 induced
      changes also reduced the functional capacity of the mature populations to
      stimulate T cells in auto and allogenic mixed lymphocyte reactions (MLR). IL-2
      had no effect on differentiation of monocytes. Thus IL-4 and IFN-gamma are seen
      to induce the development of stimulatory macrophages while IL-10 promotes
      differentiation of monocytes to mature phagocytes and suppressive macrophages. It
      is concluded that mature macrophage phenotype is 'plastic' and under the control
      of T-cell-derived mediators. Furthermore, within the differentiating monocytes,
      phenotypic change appears to carry with it functional change, thus retaining the
      relationship between antigen expression and activity in the mature macrophage
      populations.

PMID- 9176097
TI  - Phenotypic and functional characterization of a new human macrophage cell line
      K1m demonstrating immunophagocytic activity and signalling through HLA class II.
AB  - A human macrophage line, designated K1m, has been established from peripheral
      blood. K1m expresses a number of lineage-specific markers as well as a broad
      array of intercellular adhesion molecules. In particular, K1m expresses high
      levels of human leucocyte antigen (HLA) class I and class II. In response to
      ligation of HLA class II (HLA-DR), but not in response to ligation of HLA class
      1, K1m forms tighter homotypic aggregates and develops a striking 'stellate'
      culture phenotype. K1m also expresses Fc receptors for immunoglobulin G (IgG)
      (CD64, CD32, and CD16) and can be shown to phagocytose polystyrene latex beads,
      as well as neuroblastoma cells in the presence of tumour-specific monoclonal
      antibody (mAb). The K1m cell line should therefore prove useful for studying both
      signalling through macrophage HLA class II and immunophagocytosis.

PMID- 9176098
TI  - C2-ceramide and C6-ceramide inhibited priming for enhanced release of superoxide
      in monocytes, but had no effect on the killing of leukaemic cells by monocytes.
AB  - Ceramide acts as an intracellular second messenger in cellular signal
      transduction. We examined the effects of two cell-permeable ceramides, C2
      ceramide and C6-ceramide, on human monocyte functions. After monocytes were
      primed with lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma) for 18 hr in
      suspension culture, they produced a high amount of superoxide (O2-) when
      triggered by phorbol myristate acetate. C2- or C6-ceramide inhibited O2- release
      from monocytes primed with LPS (1 ng/ml) or IFN-gamma (100 U/ml), but did not
      affect unprimed monocytes. An analogue, C2-dihydroceramide, was inactive. C2
      ceramide was most effective at 6 microM, and C6-ceramide at 60 microM. C2- or C6
      ceramide at these concentrations was not toxic for monocytes, as assessed by
      trypan blue exclusion and by the 3-[4, 5-dimethylthiazol-2-y1]-2,5 diphenyl
      tetrazolium bromide (MTT) assay which measures the ability of live cells to
      produce formazan. C2-ceramide (20 microM) had no effect on the killing of
      leukaemic cells (HL-60 and K562 cells) by monocytes treated with IFN-gamma, LPS,
      or both for 18 hr, with killing assessed by an 111 Indium-releasing assay. C2
      ceramide (20 microM) induced secretion of low amounts of tumour necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) from the monocytes. But C2
      ceramide did not alter the higher secretion of TNF-alpha or IL-1 beta from
      monocytes treated with IFN-gamma or LPS. Thus the cell-permeable ceramides acted
      like antagonists of LPS, rather than analogues of LPS, as has been proposed. The
      results here showed that the signal transduction pathway for O2- release by
      monocytes differed from that for the cytolysis of leukaemic cells, and confirmed
      that oxygen radicals are not involved in cytolysis.

PMID- 9176099
TI  - Alleviation of insulitis in NOD mice is associated with expression of transgenic
      MHC E molecules on primary antigen-presenting cells.
AB  - Major histocompatibility complex (MHC) class II genes are important in the
      pathogenesis of insulin-dependent diabetes mellitus (IDDM) both in the mouse and
      in man. The non-obese diabetic (NOD) mouse, which is a good model for human IDDM,
      has a particular MHC class II with an A complex consisting of A alpha d and the
      unique A beta g7 chain, as well as an absent E molecule due to a deletion in the
      Ea promoter region. Transgenic insertion of a functional Ea gene protects against
      insulitis and diabetes, but when the transgene expression is restricted to
      certain compartments of the immune system by deleting parts of the promoter
      region, the protection against insulitis is disrupted. We have analysed three
      promoter-mutated lines where one lacks expression on B cells and has a reduced
      expression on approximately 1/3 of the dendritic cells and macrophages (Sma), one
      lacks thymic cortical expression and has a slightly reduced B-cell expression
      (delta X), and one lacks expression in the thymic medulla, on macrophages,
      dendritic cells and about half of the B cells (delta Y). None of these lines is
      protected against insulitis, but Sma and delta X display a reduced intensity of
      insulitis, with an average of 10-15% of the islets infiltrated in each mouse,
      while delta Y resembles non-transgenic mice with 30-35% infiltrated islets. Bone
      marrow chimeras between Sma and delta Y mice demonstrate that peripheral cells of
      Sma origin reduce insulitis significantly when developed in the delta Y host,
      while insulitis is enhanced when delta Y bone marrow is given to Sma mice. This
      shows that E expression on the primary antigen-presenting macrophages and
      dendritic cells is of crucial importance to the alleviation of insulitis.

PMID- 9176100
TI  - Proliferation and apoptosis of follicular lymphocytes: relationship to follicular
      dendritic cell-associated clusters.
AB  - Experiments were designed to determine the in vivo cell-cycle phase of
      lymphocytes in secondary lymphoid follicles, and whether B-cell proliferation and
      apoptosis occur within follicular dendritic cell (FDC)-associated clusters. Using
      frozen serial sections of human tonsils, lymphoid follicles were stained to
      reveal histone H3 mRNA, as an S-phase marker, using in situ hybridization, and
      stained immunohistochemically with antibodies against cyclin E as a late G1 phase
      marker, cyclin B1 and p34cdc2 as S-G2-M phase markers, and Ki-67 as a marker of
      cycling cells. Each LF was divided into five zones: mantle zone, outer zone,
      apical light zone, basal light zone and dark zone, with the help of haematoxylin
      and eosin staining, and a CD23 immunostain. The rate of occurrence of positively
      labelled cells was calculated by dividing the number of positive cells by the
      number of all cells in each zone. The cells that were positive for cyclin E,
      histone H3 mRNA, cyclin B1, p34cdc2, and Ki-67 were found most frequently in the
      dark zone (54.5 +/- 6.6%, 22.0 +/- 5.7%, 36.7 +/- 14.5%, 40.0 +/- 10.2%, and 59.0
      +/- 13.4%, respectively), followed by the outer zone (52.7 +/- 7.8%, 14.9 +/-
      4.1%, 22.9 +/- 9.7%, 24.9 +/- 7.9%, and 44.6 +/- 12.3%, respectively), showing
      that both the outer zone and the dark zone contain many proliferating
      lymphocytes. Furthermore, FDC-associated clusters and free lymphocytes were
      obtained from enucleated germinal centres, using enzymatic digestion. The rates
      of occurrence of cells that were positive for cyclin B1 and Ki-67 within the
      clusters (7.2 +/- 1.9% and 37.9 +/- 10.5% respectively) were significantly lower
      than those of free lymphocytes outside the clusters (22.2 +/- 4.0% and 62.8 +/-
      14.0%, respectively). The rates of occurrence of apoptotic bodies and cells
      within the clusters, as detected by in situ tailing or in situ nick translation
      (0.2 +/- 0.4% and 0.4 +/- 0.4%, respectively) were significantly lower than those
      outside the clusters (1.1 +/- 0.3, 1.6 +/- 0.5%, respectively). These results
      suggest that FDC-associated clusters are not the site of proliferation, and that
      they rarely contain apoptotic bodies and cells of B lymphocytes.

PMID- 9176102
TI  - Calcium pyrophosphate dihydrate crystals activate MAP kinase in human
      neutrophils: inhibition of MAP kinase, oxidase activation and degranulation
      responses of neutrophils by taxol.
AB  - The activation of MAP kinase in human neutrophils stimulated by both uncoated and
      plasma-opsonized crystals of triclinic calcium pyrophosphate dihydrate (CPPD) was
      investigated. The effect of taxol on MAP kinase activation and on the responses
      of neutrophils stimulated by plasma-opsonized crystals was determined. MAP kinase
      activation was identified and quantified in Mono Q chromatography separated
      fractions of neutrophils that had been incubated with CPPD crystals by measuring
      [gamma-32P]adenosine triphosphate (ATP) phosphorylation of myelin basic protein
      and using immunoblotting techniques. Human neutrophils were incubated with taxol
      (0-50 microM), added to plasma-opsonized CPPD (50 mg/ml) and MAP kinase
      activation, chemiluminescence, superoxide anion generation, lysozyme and
      myeloperoxidase release were monitored. Both uncoated and plasma coated CPPD
      crystals induced a large increase in MAP kinase activity in neutrophils over
      control levels within 1 min of incubation. Pretreatment of neutrophils with taxol
      was able to suppress this activation of MAP kinase. Taxol produced a
      concentration-dependent inhibition of opsonized CPPD-induced neutrophil
      chemiluminescence, superoxide anion production and myeloperoxide release. Taxol
      at 28 microM also significantly inhibited chemiluminescence, superoxide anion
      production and myeloperoxidase release from neutrophils stimulated by opsonized
      zymosan. This is the first report of crystal-induced activation of MAP kinase in
      neutrophils. Microtubule-associated processes, such as signal transduction,
      secretion and phagocytosis are involved in particulate-induced neutrophil
      responses. We have suggested that the inhibitory effect of taxol observed in this
      work is due to its stabilizing effect on microtubules and disruption of MAP
      kinase activation associated with microtubules.

PMID- 9176101
TI  - Langerhans' cells produce type IV collagenase (MMP-9) following epicutaneous
      stimulation with haptens.
AB  - For initiation of the contact hypersensitivity response, epidermal Langerhans'
      cells (LC) migrate from the epidermis to draining nodes via afferent lymphatics
      by passing through the basement membrane. In this study, we examined production
      of matrix metalloproteinases (MMPs) in LC-enriched epidermal cells to clarify the
      type of enzymes involved in LC transmigration through the basement membrane.
      Using gelatine enzymography and immunoblotting analysis, 95,000 MW type IV
      collagenase (MMP-9) was found to be produced by LC-enriched epidermal cells.
      Analysis of the kinetics of MMP-9 expression showed that its production was
      induced within 6 hr after application of 2,4,6-trinitrochlorobenzene (TNCB),
      substantially increased between 12 hr and 24 hr, and then decreased to the normal
      level by 7 to 10 days. Other haptens, such as 2,4-dinitrochlorobenzene and 2,4
      dinitrofluorobenzene, also induced MMP-9 expression. Fluoroescence-activated cell
      sorter analysis revealed that LC were one of the major cell types to express MMP
      9 in response to TNCB. In addition, highly enriched LC from sensitized skin were
      shown to express strong gelatinolytic activity. These results indicate that LC by
      themselves, as well as other epidermal cells, are capable of producing MMP-9, and
      suggest that MMP-9 may contribute to proteolysis associated with transmigration
      of LC in the induction phase of contact dermatitis.

PMID- 9176103
TI  - Eosinophilia, parasite burden and lung damage in Toxocara canis infection in
      C57Bl/6 mice genetically deficient in IL-5.
AB  - C57Bl/6 mice genetically deficient in interleukin (IL)-5 (IL-5-/-) and mice with
      the normal IL-5 gene (IL-5+/+) were infected with embryonated eggs of Toxocara
      canis. IL-5+/+ mice developed a marked eosinophilia in their peripheral bloods
      and bone marrows after infection. In contrast, the number of eosinophils at these
      sites actually decreased during the acute phase of infection in IL-5-/- mice. A
      smaller number of eosinophils infiltrated the lung, liver, heart and skeletal
      muscle of infected IL-5-/- mice than those of infected IL-5+/+ mice. Eosinophils
      were not produced in cultures of bone marrow cells from either IL-5+/+ or IL-5-/-
      mice which were stimulated with excretory secretory antigen of T. canis larvae.
      The capacity of cells from the bone marrow to differentiate into eosinophils when
      stimulated in vitro with recombinant murine IL-5 was the same whether the cells
      were from IL-5+/+ or IL-5-/- mice. Taken together, these results show that an IL
      5-like molecule is not produced by the T. canis larvae and that IL-5 produced by
      host cells is solely responsible for the eosinophilia in mice infected with this
      nematode. The number and location of T. canis larvae were not altered in the
      absence of IL-5. In contrast, lung damage in infected IL-5-/- mice was less
      extensive than that in infected IL-5+/+ mice, although structures resembling
      Charcot-Leyden crystals were seen in the lungs of both IL-5+/+ and IL-5-/- mice.
      These results suggest that eosinophils play a role in the pathology in mice
      infected with T. canis.

PMID- 9176104
TI  - Characterization of a mast cell line that lacks the extracellular domain of
      membrane c-kit.
AB  - Expression of the c-kit proto-oncogene receptor on mast cells is essential for
      their normal proliferation and maturation as well as for several biological
      responses such as chemotaxis and attachment. In the present study we report that
      the interleukin-3 (IL-3)-dependent mast cell line CFTL-15 lacks the extracellular
      domain of the c-kit receptor. This observation was made after noting that the c
      kit ligand stem cell factor (SCF) could not prevent IL-3 deprivation-induced mast
      cell apoptosis and that CFTL-15 cells did not proliferate in response to SCF.
      Flow cytometric analysis employing monoclonal anti-c-kit antibodies, and
      immunogold labelling with analysis by electron microscopy, subsequently showed a
      diminished expression of c-kit on CFTL-15 cells. There was no identifiable
      message for the extracellular domain of c-kit in these cells, as determined by
      reverse transcriptase-polymerase chain reaction (RT-PCR). These previously
      unrecognized properties of the CFTL-15 mast cell line allowed the examination of
      other biological consequences of the lack of c-kit on mast cells. Analysing the
      ability of these cells to adhere to surface-bound fibronectin, it was found that
      addition of SCF did not increase their adhesion to this substrate, in opposition
      to what is reported with other mast cells. Similarly, CFTL-15 mast cells did not
      adhere to fibroblasts, which is known to require c-kit expression. Also, there
      was no protein tyrosine phosphorylation in these cells in response to SCF. CFTL
      15 cells underwent apoptosis on removal of IL-3 coincident with a decrease in
      endogenous Bcl-2 mRNA. Overexpression of Bcl-2 cDNA prolonged survival of Bcl-2
      transfected CFTL-15 cells upon withdrawal of IL-3. Thus, the CFTL-15 cell line
      that lacks surface c-kit is not able to proliferate in response to SCF, undergoes
      apoptosis in the presence of SCF, and does not adhere to fibroblasts. These
      results confirm earlier studies on the functional consequences of c-kit and
      provide a novel experimental model for further investigation.

PMID- 9176105
TI  - Secretion of cytokines by natural killer cells primed with interleukin-2 and
      stimulated with different lipoproteins.
AB  - Natural killer (NK) cells were shown to secrete differentially interleukins (IL),
      IL-1 alpha, IL-1 beta, IL-2, IL-8, interferon-gamma (IFN-gamma), tumour necrosis
      factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM
      CSF), and leukaemia inhibitory factor (LIF) upon stimulation with optimal
      concentrations of chylomicrons (CM), very-low-density lipoprotein (VLDL), low
      density lipoprotein (LDL), high-density lipoprotein (HDL) or acetyl-modified low
      density lipoprotein (AcLDL). CM, VLDL, LDL and AcLDL induced LIF secretion which
      was absent in nonstimulated cells. CM, VLDL, and LDL did not affect IL-1 alpha
      secretion. CM stimulated IL-8 > TNF-alpha > IL-1 alpha > IL-2 = IFN-gamma, and
      decreased seventeen-fold GM-CSF secretion. VLDL stimulated IL-8 secretion > IL-1
      alpha = IL-2 > IFN-gamma > TNF-alpha and decreased fivefold GM-CSF secretion. LDL
      stimulated IL-8 secretion > IL-1 alpha > IL-2 = IFN-gamma, it did not modify TNF
      alpha and inhibited five hundred-fold GM-CSF secretion. HDL stimulated IL-2
      secretion = IFN-gamma > IL-8, it decreased GM-CSF secretion > IL-1 alpha > IL-1
      beta > TNF-alpha without affecting LIF. AcLDL stimulated IL-8 secretion > TNF
      alpha > IL-1 alpha > IL-2 = IFN-gamma = IL-1 beta, and decreased GM-CSF secretion
      eightfold. When NK cells were primed with 10, 100 or 500 IU/ml of IL-2 before the
      addition of lipoproteins, a decrease in the secretion of cytokines was observed
      as compared with cells primed with IL-2 only. Differences in cytokine secretion
      were observed among the diverse type of lipoproteins used for cell stimulus.
      Thus, lipoproteins may condition NK cytokine secretion and cell activation.

PMID- 9176106
TI  - Mitogenic stimulation of T cells reveals differing contributions for B7-1 (CD80)
      and B7-2 (CD86) costimulation.
AB  - The requirement of accessory cells for concanavalin A (Con A) activation of T
      cells suggests delivery of a separate costimulatory signal. However, the
      costimulatory pathways involved have not been identified. These studies assess
      the role of CD28-B7-mediated costimulation during T-cell activation by Con A. The
      B7-1/B7-2 binding protein CTLA4-Ig inhibited the proliferative response of
      primary lymph node cells to either Con A or soluble anti-CD3 mAb. This
      suppression was dose dependent and could be reversed by CD28 cross-linking. CTLA4
      Ig also completely suppressed induction of interleukin-2 (IL-2) mRNA by Con A.
      CTLA4-Ig-mediated suppression was not due to blockade of the Con A 'receptor(s)'
      or of the primary activation signal (as measured by the intracellular calcium
      response). Although both B7-1 and B7-2 were up-regulated following Con A
      activation, each played a different role in proliferation and cytokine
      production. Individually, anti-B7-2 Fab partially inhibited the Con A response
      whereas anti-B7-1 Fab had no effect. However, the combination of anti-B7-1 and
      anti-B7-2 Fab completely suppressed proliferation and IL-2 production. Therefore,
      while a part of the Con A response requires B7-2, the remainder of the response
      can utilize either B7-1 or B7-2. Together, these results demonstrate that Con A
      activation of T cells requires the delivery of a separate costimulatory signal
      that is mediated almost entirely by the B7 receptors.

PMID- 9176107
TI  - Interferons alpha/beta inhibit IL-7-induced proliferation of CD4- CD8- CD3- CD44+
      CD25+ thymocytes, but do not inhibit that of CD4- CD8- CD3- CD44- CD25-
      thymocytes.
AB  - Type 1 interferons (IFN-alpha/beta) have recently been shown to inhibit
      interleukin-7 (IL-7)-induced growth and survival of early B-lineage cells. The
      CD3- CD4- CD8- (triple negative; TN) thymocytes from normal mice strongly
      proliferated upon stimulation with IL-7 in suspension, culture. Such an IL-7
      induced proliferation was suppressed by the addition of IFN-alpha/beta, but a
      fraction of the TN thymocytes still showed proliferation. The IL-7-induced growth
      of TN thymocytes from acid mice, which lack the CD44- CD25- subpopulation, was
      completely inhibited by the addition of IFN-alpha/beta. The IL-7 induced
      proliferation of CD4- CD8- thymocytes from T-cell receptor (TCR) transgenic mice,
      the majority of which are CD3+ CD44- CD25-, was resistant to IFN-alpha/beta
      mediated suppression. In fetal thymus organ cultures (FTOC), the addition of IL-7
      greatly increased the population of CD4- CD8- CD44+ CD25+ thymocytes and IFN
      alpha/beta inhibited this IL-7-driven expansion. In contrast, the addition of IL
      7 markedly decreased the percentages of CD4- CD8- CD3- CD44- CD25- cells, and IFN
      alpha/beta reversed the effect and increased the subpopulations of CD44- CD25+
      and CD44- CD25-. Finally, IFN-beta mRNA was found to be expressed in the thymus.
      The data suggest that type I interferons inhibit IL-7-driven proliferation of TN
      thymocytes, but do not block the normal differentiation process.

PMID- 9176108
TI  - Treatment with anti-LFA-1 alpha monoclonal antibody selectively interferes with
      the maturation of CD4- 8+ thymocytes.
AB  - Maturation of T lymphocytes in the thymus is driven by signals provided by
      soluble factors and by the direct interaction between thymocytes and stromal
      cells. Although the interaction between T-cell receptor (TCR) and major
      histocompalibility complex (MHC) molecules on stromal cells is crucial for T-cell
      development, other accessory molecules seem to play a role in this process. In
      order to better understand the role of lymphocyte function-associated antigen-1
      (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) molecules in thymocyte
      maturation, mice were treated from birth with saturating doses of non-cytolytic
      specific monoclonal antibodies. The effect of this treatment on thymocyte
      subpopulations and the expression of CD3 and TCR-alpha beta by these cells was
      investigated by flow cytometry. Our data demonstrated that the effective
      saturation of LFA-1 alpha chain in the thymus, but not ICAM-I or LFA-I beta
      chain, selectively interfered with the maturation of CD8+ T cells, as manifested
      by a marked reduction in the frequency of CD4-8+ thymocytes expressing high
      levels of CD3 and TCR-alpha beta. This selective reduction was also observed in
      peripheral blood mononuclear cells and spleen cells. The analysis of the
      frequencies of various V beta TCR showed that CD4-8+ thymocytes were globally
      affected by the treatment. These results underline the importance of the
      interaction between LFA-1 and its ligands in the maturation of CD8+ T cells and
      document the existence of different molecular requirements for the
      differentiation of CD4+ and CD8+ T cells.

PMID- 9176109
TI  - Protein kinase C isotypes theta, delta and eta in human lymphocytes: differential
      responses to signalling through the T-cell receptor and phorbol esters.
AB  - The repertoire of novel and atypical protein kinase C (PKC) isotypes present in
      human T cells and their subcellular localization have not been fully
      characterized. We detected calcium-independent PKC activity in whole cell
      fractions from unstimulated peripheral blood lymphocytes (PBL). Towards an
      understanding of the role of PKC isoforms in lymphocyte activation we have
      studied the expression of calcium-independent PKC isoforms theta, delta and eta
      in PBL. With isoformspecific antibodies we detected the presence of PKC theta and
      delta in whole cell fractions from unstimulated human PBL by Western blot
      analysis. In addition, immunocytochemical analysis confirmed the presence of the
      novel PKC isoform PKC eta in PBL. Using immunocytochemistry, PKC theta, delta and
      eta had distinct patterns of redistribution following activation by phorbol
      myristate acetate (PMA). However, signalling through the T-cell receptor (TCR)
      did not appear to induce such changes in isoenzyme redistribution. These findings
      indicate that activation of lymphocytes either through the TCR-CD3 complex or
      with PMA induces different signalling pathways with respect to calcium
      independent isoenzymes. Signalling through receptors other than the CD3 complex
      may be involved in activation of these isotypes.

PMID- 9176110
TI  - Differential G-protein expression during B- and T-cell development.
AB  - The molecular mechanisms underlying B- and T-cell development are, as yet, poorly
      understood. However, as G proteins regulate a diverse range of biological
      responses including growth, proliferation and differentiation, we have
      investigated differential expression of G proteins during B- and T-cell
      development with the aim of identifying key signals involved in lymphocyte
      maturation. Differential expression of beta 1/2 and alpha-subunits of the Gs-, i-
      and q-families was found throughout lymphoid development. Most strikingly, G
      alpha i1 and G alpha i1 were very weakly, or not expressed in pre-, immature and
      mature B cells, thymocytes or mature T cells, but strongly induced in mature B
      lymphoblastoid cell lines, some of which have been used as models of germinal
      centre B cells, suggesting that expression of these G proteins may correlate with
      the later stages of B-cell development. In contrast, G alpha 16 expression was
      highest in T cells and pre-B cells and progressively declined with B-cell
      maturation. These findings suggest that G proteins, and the signals they
      regulate, such as ion channels and/or adenylate cyclase (G alpha s/i) and
      phospholipase C (G beta gamma and G alpha 11/16) are differentially regulated in
      lymphoid cells in a maturation-and lineage-dependent manner.

PMID- 9176111
TI  - Rejection of cardiac allografts by T cells expressing a restricted repertoire of
      T-cell receptor V beta genes.
AB  - We have recently shown that T cells infiltrating cardiac allografts early in
      graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this
      study we tested whether this limited repertoire of V beta genes is important for
      graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes
      infiltrating ACI heart allografts 2 days after transplantation. This cell line is
      composed of CD4+ T cells that primarily recognize the class II RTI.B major
      histocompatibility complex (MHC) molecule expressed by the donor graft. This cell
      line precipitated acute rejection of donor hearts with a median survival time
      (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW
      recipients. This rate of graft rejection was significantly (P < 0.0007)
      accelerated when compared with a MST of 60 days for allografts in irradiated
      control recipients. The AL2-L3-mediated acceleration of graft rejection was donor
      specific as WF third-party heart allografts were rejected with a delayed tempo
      (MST = 28.5 days). The V beta repertoire of this cell line was primarily
      restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide
      sequence analysis of the beta-chain cDNAs from this cell line demonstrated that
      the restricted use of the V gene repertoire was not shared with the N, D and J
      regions. A wide variety of CDR3 loops and J beta genes were used in association
      with selected V beta genes. These data provide evidence for the role a restricted
      repertoire of V beta genes plays in cardiac allograft rejection in this model.
      The restricted usage of the V beta repertoire in an early T-cell response to
      allografts may provide the opportunity to therapeutically disrupt the rejection
      reaction by targeting selected T-cell populations for elimination at the time of
      organ transplantation.

PMID- 9176112
TI  - Characterization of Marek's disease herpesvirus-specific cytotoxic T lymphocytes
      in chickens inoculated with a non-oncogenic vaccine strain of MDV.
AB  - Previously we have reported that reticuloendotheliosis virus (REV)-transformed
      cell lines expressing Marek's disease virus (MDV) genes pp38, meq or gB were
      lysed by syngeneic MDV-specific splenocytes from major histocompatibility complex
      (MHC):B9B19 and MHC:B1B21 chickens. In contrast, REV-transformed cell lines
      expressing the MDV gene ICP4 were only lysed by syngeneic MDV-specific
      splenocytes from MHC:B21B21 chickens. In this study we report that this syngeneic
      cell-mediated immune response is induced by cytotoxic T lymphocytes (CTL).
      Splenocytes from MDV vaccine strain, SB-1 inoculated MHC:B19B19 and MHC:B21B21
      chickens, depleted for CD4+, CD8+, TCR gamma delta +, TCR alpha beta 1+ and/or
      TCR alpha beta 2+ cells, were used as effector cells in chromium-release assays.
      Effector cells depleted of CD8+ or TCR alpha beta 1+, but not TCR gamma delta +
      or TCR alpha beta 2+, markedly reduced the MDV-specific release. Depletion of
      CD4+ effector cells did not influence the specific release significantly. This is
      the first report on identification of virus-specific CD8+ CTL in chickens
      inoculated with a non-oncogenic vaccine strain of MDV.

PMID- 9176113
TI  - Transforming growth factor-beta induced by live or ultraviolet-inactivated equid
      herpes virus type-1 mediates immunosuppression in the horse.
AB  - Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus
      type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if
      incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in
      the sera of ponies also inhibited T-cell response to phytohaemagglutinin.
      Increased levels of circulating activated transforming growth factor-beta 1 (TGF
      beta 1) were detected, and the suppressive activity of the serum could be
      reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which
      exhibited circulating TGF-beta 1 activity succumbed to infection while the ones
      with similar magnitudes of T-cell responses, but no TGF-beta 1 activity, were
      protected. A definition of this immunosuppressive mechanism and its mode of
      induction must be central to the design of vaccines and to an understanding of
      the pathogenesis of EHV-1.

PMID- 9176114
TI  - The diverse expression of immunity in humans at distinct states of Onchocerca
      volvulus infection.
AB  - This study examined the development and persistence of immunity in humans
      presenting defined states of Onchocerca volvulus infection, i.e. in exposed
      endemic control individuals without microfilaridermia and clinical disease, in
      patients with patent or post-patent onchocerciasis, and in patients concurrently
      infected with Mansonella perstans. Onchocerca volvulus antigen (OvAg)-specific
      cellular reactivity was significantly diminished in microfilariae (mf)-positive
      patients, while the highest reactivity was measured in exposed but mf-negative
      endemic controls, those being free of any clinical signs of onchocercal disease.
      In patients who became post-patent, responses to OvAg were significantly
      augmented, but did not approach entirely the magnitude observed in endemic
      controls. In onchocerciasis patients with concurrent mansonelliasis, cellular
      unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated
      permanently by repeated ivermectin therapy. Cells from mf-positive onchocerciasis
      patients produced significantly less interferon-gamma (IFN-gamma) (P < 0.01) and
      interleukin-5 (IL-5) (P < 0.05) in response to OvAg than those taken from endemic
      controls or post-patent individuals in whom IFN-gamma and IL-5 production was
      similarly high. In contrast, both OvAg-driven as well as spontaneous IL-10
      secretion was higher in mf-positive patients than in endemic controls or post
      patent cases. In all individuals examined, serological recognition of OvAg by
      immunoglobulins was dominated by IgG4; in mf-positive patients OvAg of 205,000
      12,000 molecular weight (MW) were strongly bound. In post-patent individuals, and
      similarly in endemic controls. OvAg recognition by IgG4 varied from intense (with
      numerous antigens being recognized) to weak or absent antigen binding.
      Significantly elevated OvAg-specific IgG isotypes were measured in mf-positive
      onchocerciasis patients in comparison with endemic controls or post-patent
      individuals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, but
      IgG4 was lower in endemic controls compared with post-patent onchocerciasis
      patients. The ratios of IgG4/IgG1 differed (P < 0.001) between endemic controls
      and mf-positive or post-patent onchocerciasis patients, with IgG4/IgG1 ratios of
      R < 3.0 being characteristic for endemic controls and post-patent O. volvulus
      infection. In conclusion, this cross-sectional immunoepidemiological
      investigation showed that distinct states of O. volvulus infection correlate with
      a particular cellular and humoral immune response. The mf-free condition appeared
      to be associated with a vigorous parasite-specific cellular reactivity and a
      particular cytokine production profile, while concurrent M. perstans infection
      depressed OvAg-specific cellular responsiveness. Antibody responses, in all
      likelihood, reflected the intensity and state of infection, and not the degree of
      acquired immunity protective against parasite aggregation.

PMID- 9176115
TI  - Evidence for a reduced chemokine response in the lungs of beige mice infected
      with Mycobacterium avium.
AB  - The basis of the increased susceptibility of beige mice to Mycobacterium avium
      infections is still not clearly understood. In this study we examined the growth
      of three virulent strains of M. avium in beige mice and normal C57BL/6 controls.
      Depletion of natural killer (NK) cells by administration of anti-asialo GM1
      antisera did not affect the growth of M. avium in any of the groups of animals.
      Similarly, interferon-gamma (IFN-gamma) gene-disrupted mice were more susceptible
      to infection than control mice but the growth of M. avium was not further
      affected by NK-cell depletion. In terms of effector immunity, beige mice showed
      enhanced expression of IFN-gamma and tumour necrosis factor-alpha (TNF-alpha)
      when compared with wild-type C57BL/6 mice. In agreement with these results; I-A
      and interferon-inducible protein (IP-10) expression was also higher in beige mice
      than in wild-type animals, as was expression of the chemokines macrophage
      inflammatory protein-2 (MIP-2) and macrophage chemotactic protein (MCP-1) during
      latter stages of the infection. However, over the first few weeks of the
      infection, when the susceptibility of the beige mouse lung first becomes evident,
      MIP-1 beta and MIP-2 chemokine expression in the lungs was lower in beige mice
      than in wild-type animals. These data indicate, therefore, that the increased
      susceptibility of beige mice to M. avium infection in the lung is not due to lack
      of NK-cell activity, nor can it be explained in terms of the effector cytokine
      response. Instead, the lower early expression of the neutrophil chemoattractants
      MIP-1 beta and MIP-2 in the lungs of beige mice tends to suggest that the
      enhanced susceptibility of these mice to M. avium infection may be due in part to
      defective recruitment of neutrophils or other cells responsive to these specific
      chemokines.

PMID- 9176116
TI  - Analysis of the local kinetics and localization of interleukin-1 alpha, tumour
      necrosis factor-alpha and transforming growth factor-beta, during the course of
      experimental pulmonary tuberculosis.
AB  - A mouse model of pulmonary tuberculosis induced by the intratracheal instillation
      of live and virulent mycobacteria strain H37-Rv was used to examine the
      relationship of the histopathological findings with the local kinetics production
      and cellular distribution of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta).
      The histopathological and immunological studies showed two phases of the disease:
      acute or early and chronic or advanced. The acute phase was characterized by
      inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and
      bronchial wall with formation of granulomas. During this acute phase, which
      lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha
      immunostained activated macrophages were observed principally in the interstium
      intralveolar inflammatory infiltrate and in granulomas. Electron microscopy
      studies of these cells, showed extensive rough endoplasmic reticulum, numerous
      lysosomes and occasional mycobacteria. Double labelling with colloid gold showed
      that TNF-alpha and IL-1 alpha were present in the same cells, but were confined
      to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to
      cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their
      respective mRNAs were elevated in the early phase, particularly at day 3 when the
      bacillary count decreased. A second peak was seen at days 14 and 21-28 when
      granulomas appeared and evolved to full maturation. In contrast, TGF-beta
      production and numbers of immunoreactive cells were low in comparison with the
      advanced phase of the disease. The chronic phase was characterized by
      histopathological changes indicative of more severity (i.e. pneumonia, focal
      necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha
      and IL-1 alpha production that coincided with the highest level of TGF-beta. The
      bacillary counts were highest as the macrophages became large, vacuolated foamy
      cells, and containing numerous bacilli with immunoreactivity to mycobacterial
      lipids and lipoarabinomannan (LAM). These macrophages displayed poor and scarce
      TNF-alpha and IL-1 alpha immunostaining but still strong immunoreactivity to TGF
      beta. These cytokine production kinetics and the spatial relationship between
      immunostained cells and lung lesions corroborate the important role of TNF-alpha
      and IL-1 alpha in the constitution of granulomas and immune protection during the
      early phase of the infection, and also suggest an important if not primary role
      for TGF-beta in the immunopathogenesis of the advanced forms of pulmonary
      tuberculosis.

PMID- 9176117
TI  - Correlates of protection induced by live Aro- Salmonella typhimurium vaccines in
      the murine typhoid model.
AB  - Live attenuated salmonella vaccines generally confer better protection than
      killed vaccines. The immune responses in BALB/c mice elicited by immunization
      with a live attenuated Aro Salmonella typhimurium vaccine given orally,
      intravenously or subcutaneously were compared with those elicited by killed whole
      cell vaccines (acetone or heat-treated) given subcutaneously. Live vaccines given
      by all routes elicited higher interleukin-2 (IL-2) and interferon-gamma (IFN
      gamma) responses in spleen cells against an alkali-treated whole-cell salmonella
      lysate than did killed vaccines. Live and killed vaccines elicited high total
      antibody levels to smooth lipopolysaccharide (LPS) (enzyme-linked immunosorbent
      assay), but all live vaccine regimes elicited higher IgG2a, suggesting a Th1
      response. Oral and intravenous vaccination with live organisms elicited IgA
      against smooth LPS which subcutaneous vaccination with live or killed salmonellae
      failed to evoke. Western blots using rough whole-cell lysates showed that all
      vaccines elicited a varied anti-protein response; however, all groups immunized
      with live organisms recognized three unidentified bands of MW 52,000, 46,000 and
      18,000 which were consistently absent in groups immunized with killed organisms.
      The results indicate that immunization with live aroA salmonellae elicited a Th1
      type of response, including bystander T-cell help to LPS, and a response to
      proteins not seen in mice that received killed vaccines.

PMID- 9176118
TI  - The in vivo antibody response against exogenous antigens is not influenced by the
      mouse Bcg (Nramp1) gene.
AB  - The mouse Nramp1 (Bcg) gene on chromosome 1 exerts pleiotropic effects on
      macrophage function. The gene is known to affect presentation of mycobacteria,
      and other antigens in vitro, so that macrophages carrying the resistant Bcg
      allele better support the proliferation of antigen-specific T cells compared with
      macrophages of the sensitive phenotype. To determine whether the Bcg allele could
      affect in vivo the antibody response to antigens not related to mycobacterial
      infections, we tested the primary and secondary responses to sheep red blood
      cells (SRBC) and glycosylated bovine insulin (G-insulin) in two pairs of Bcg
      congenic strains: BALB/c (Bcgs) versus BALB/c.CD2 (Bcgr), and B10.A (Bcgs) versus
      B10Ar (Bcgr), and in C57BL/10ScSn (B10; Bcgs) and A/J (Bcgr) mice. Furthermore,
      the antigen-specific proliferative responses of T cells primed in vivo by protein
      antigens were also tested in Bcg congenic mice. We found no significant
      difference in in vivo antibody response either to SRBC or G-insulin between the
      Bcgr and Bcgs strains. The magnitude of in vitro antigen-specific proliferation
      of lymph node cells sensitized in vivo by hen egg lysozyme (HEL) or chicken
      ovalbumin (OVA) was also similar in Bcgs and Bcgr congenic mice. However, we have
      documented a higher antigen-presenting capacity of Bcgr macrophages in in vitro
      antigen-specific proliferation to OVA. Since the macrophages are the only cells
      in which the Nramp1 gene is expressed, we suggest that the activity of other
      types of antigen-presenting cells masks the effect of the Bcgr allele on antigen
      presentation in vivo.

PMID- 9176119
TI  - Sequence, specificity and crystallization of an oestrone-3-glucuronide antibody
      (3910).
AB  - We describe the specificity profile and V region sequences of a high-affinity
      monoclonal antibody (mAb), 3910, directed against oestrone-3-glucuronide (E3G).
      Inhibition studies show that the D-ring is critical for steroid specificity,
      while the glucuronic acid attached to the A ring is required for high binding
      affinity, suggesting that both 'ends' of the E3G ligand are recognized. The VH
      domain is encoded by a gene from the VH7183 family, while VL appears to be
      encoded by the Vk5.1 gene (kappa II subgroup) with a deletion of six residues
      from complementarity-determining region-1 (CDR1). The VH CDR3 is 10 amino acid
      residues in length, of which D/N contributes five residues. Comparison of VH CDR
      of 3910 with those of mAb against progesterone (DB3) and digoxin (26-10, 40-50),
      for which crystal structures have been determined, suggests that aromatic side
      chains are important for E3G binding and that tyrosine residues H50, H97 and H100
      may interact with the ligand. The Fab fragment of 3910 has been crystallized in
      its native and steroid (E3G and oestriol-3-glucuronide) complexed forms. An X-ray
      diffraction data set to 3 A resolution has been collected for the native Fab.

PMID- 9176120
TI  - Expression of rat CD59: functional analysis confirms lack of species selectivity
      and reveals that glycosylation is not required for function.
AB  - This study reports the expression and functional characterization of the rat
      analogue of the human complement regulatory molecule CD59. We here describe the
      expression in chinese hamster ovary (CHO) cells of rat CD59 and a modified rat
      CD59 in which an N-glycosylation site at Asn-16 has been deleted by point
      mutation. The complement-inhibiting capacity of these two forms of rat CD59 has
      been analysed and compared. Expressed rat CD59 efficiently inhibited complement
      lysis of CHO cells when rat serum was used as a source of complement and also
      inhibited lysis by complement from all other species tested, confirming that rat
      CD59 displayed little or no species restriction of activity. Blocking of
      expressed rat CD59 with a monoclonal antibody abrogated the inhibition of lysis
      for all sources of complement, confirming that the expressed molecule was
      responsible for the protection. The glycosylation mutant had a much reduced
      molecular weight on sodium dodecyl sulphate-polyacrylamide gel electrophoresis
      (SDS-PAGE) (12,000 MW as compared with 20,000-28,000 MW for unmutated),
      confirming that it was unglycosylated. However, the glycosylation mutant had
      complement-inhibitory activity which was at least as potent as that of the
      unmutated molecule, demonstrating that the large, N-linked carbohydrate moiety
      was not required for function.

PMID- 9176121
TI  - Mechanisms of complement resistance induced by non-lethal complement attack and
      by growth arrest.
AB  - Non-lethal complement (C) attack on K562 cells has been shown to induce a
      transient resistance to lethal amounts of C. We have previously shown that
      incubation of K562 with phorbol 12-myristate 13-acetate (PMA) caused an increase
      in both CD59 expression and resistance to C killing and we were interested to
      examine whether non-lethal C attack caused a similar effect. We here demonstrate
      that expression of the C inhibitors decay-accelerating factor (DAF), membrane
      cofactor protein (MCP) and CD59 was unaltered on K562 after non-lethal C attack
      and that neutralization of these inhibitors with specific blocking antibodies did
      not reverse the induced resistance. In an effort to understand the mechanisms of
      resistance we searched for other conditions that might induce C resistance in
      K562 cells. Growth-arrested cells showed a similar degree of resistance to C
      killing. The levels of DAF and MCP on these cells were unaltered whereas
      expression of CD59 was markedly reduced. Non-lethal C attack on these growth
      arrested cells induced a further increase in resistance to C killing, suggesting
      that the mechanisms of resistance were not identical. Indeed, resistance of non
      lethally attacked cells was completely lost within 8 hr of attack whereas
      resistance of growth-arrested cells was detectable for up to 48 hr after
      returning to cell cycle. These data demonstrate that C resistance induced by two
      distinct strategies is not mediated by the known membrane C inhibitors.
      Resistance may be a result of the expression of a novel inhibitor or due to
      metabolic depletion, a likely common consequence of non-lethal C attack and
      induction of growth arrest, implying that cells take an active role in C-mediated
      killing.

PMID- 9176122
TI  - Food sensitivity and the pathogenesis of atopic dermatitis.

PMID- 9176123
TI  - Dietary regimens for atopic dermatitis in childhood.

PMID- 9176124
TI  - Intestinal involvement in atopic disease.

PMID- 9176126
TI  - Cow's milk allergy.

PMID- 9176125
TI  - Prevention of food allergy and atopic disease.

PMID- 9176127
TI  - Peanut allergy: recent advances and unresolved issues.

PMID- 9176128
TI  - The dietetic and nutritional management of food allergy.

PMID- 9176129
TI  - Inhibition of glucose transport in human red blood cells by adenosine
      antagonists.
AB  - Previous studies have suggested that adenosine antagonists can interfere with
      normal glucose uptake in perfused rat heart. In the present studies, fluorine-19
      nuclear magnetic resonance spectroscopy was used to study the effect of the
      adenosine antagonist, BW-A1433U, on the equilibrium exchange of fluorinated
      glucose analogs in human erythrocytes. Studies of the equilibrium exchange of
      both 2-fluoro-2-deoxy-D-glucose and 3-fluoro-3-deoxy-D-glucose with either one
      dimensional magnetization transfer or two-dimensional exchange spectroscopy were
      performed, and significant inhibition was observed in all cases. From
      concentration-dependent studies, an inhibition constant for the equilibrium
      exchange measured at 37 degrees C of 24 microM was determined.

PMID- 9176130
TI  - Chimeric calsequestrin and its targeting to the junctional sarcoplasmic reticulum
      of skeletal muscle.
AB  - Calsequestrin (CS) is the junctional sarcoplasmic reticulum (jSR) Ca2+ binding
      protein responsible for intraluminal Ca2+ storage. The targeting mechanisms of CS
      to the jSR are yet to be unraveled. The nine-amino acid epitope of the influenza
      virus hemoagglutinin (referred to as HA1) was added at the COOH-terminal of CS by
      polymerase chain reaction cloning. The HA1-tagged CS cDNA was transiently
      transfected in either HeLa cells, myogenic cell lines, such as C2 and L8 cells,
      myoblasts of rat skeletal muscle primary cultures, or regenerating soleus muscle
      fibers of adult rats. The expression and intracellular localization of chimeric
      CS-HA1 were monitored by epifluorescence and confocal microscopy using either
      anti-CS antibodies or anti-HA1 antibodies. About 30% of transfected HeLa cells
      and 20-40% of myogenic cells expressed CS-HA1 into intracellular compartments,
      such as the perinuclear cisternae of endoplasmic reticulum (ER). Myoblasts of
      newborn rat skeletal muscles were first transfected and subsequently stimulated
      to differentiate into myotubes. CS-HA1 was detected in approximately 20% of
      transfected myotubes and did not affect CS distribution in myotubes. In the
      soleus muscle of adult rat, intramuscular injection of bupivacaine induced
      necrosis followed by regeneration. In vivo transfection of HA1-tagged CS cDNA in
      regenerating skeletal muscles determined expression in a few skeletal muscle
      fibers; CS-HA1 was localized only in jSR, as judged by confocal microscopy of
      longitudinal sections. The present results show that chimeric CS-HA1 is correctly
      sorted to ER/SR compartments and that the free COOH-terminal is not requested for
      sorting, retention, and segregation of CS to the SR.

PMID- 9176131
TI  - Nordihydroguaiaretic acid depletes ATP and inhibits a swelling-activated, ATP
      sensitive taurine channel.
AB  - The mechanism by which nordihydroguaiaretic acid (NDGA), a lipoxygenase
      inhibitor, prevents swelling-activated organic osmolyte efflux was examined in
      the human hepatoma cell line Hep G2. When swollen in hypotonic medium, Hep G2
      cell exhibited a regulatory volume decrease that was associated with the release
      of intracellular taurine, an amino acid found at a concentrations of 22.0 +/- 2.5
      nmol/mg protein (approximately 5 mM) in these cells. Rate coefficients for
      swelling-activated [3H]taurine uptake and efflux were unaffected when
      extracellular taurine was increased from 0.1 to 25 mM, indicating that taurine is
      released via a channel. Taurine efflux was rapidly activated after cell swelling
      and immediately inactivated when cells were returned to normal size by
      restoration of isotonicity. Swelling-activated taurine efflux was not altered by
      replacement of extracellular Na+ with choline+ or K+ but was inhibited when
      cellular ATP levels were decreased with a variety of chemical agents, consistent
      with an ATP-regulated channel previously described in other cell types. NDGA
      inhibited swelling-activated [3H]taurine efflux in Hep G2 cells at concentrations
      of 50-150 microM; however, these same concentrations of NDGA also lowered cell
      ATP levels. Likewise, ketoconazole, an inhibitor of cytochrome P-450
      monoxygenases, inhibited [3H]taurine efflux only at concentrations at which cell
      ATP levels were also lowered. In contrast, other inhibitors of cyclooxygenase
      (indomethacin, 100 microM) or of lipoxygenases (caffeic acid, 100 microM), as
      well as arachidonic acid itself (100 microM), had no effect on either taurine
      efflux or cell ATP. The present findings characterize a swelling-activated, ATP
      sensitive osmolyte channel in Hep G2 cells and demonstrate that inactivation of
      the channel by NDGA is related to the ability of this drug to deplete cellular
      ATP.

PMID- 9176132
TI  - Modulation of Ca2+ transients and tension by intracellular EGTA in intact frog
      muscle fibers.
AB  - Ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) was
      used as an intracellular Ca2+ chelator to shorten the duration of the Ca2+
      transient and to determine the rate-limiting steps in relaxation of frog skeletal
      muscle at 10 and 20 degrees C. Incubation with the acetoxymethyl ester of EGTA
      (EGTA-AM) produced a linear approximately twofold increase in the rate of fall in
      twitch Ca2+ concentration ([Ca2+]) over 0-70 min at 10 degrees C. The rate of
      relaxation initially increased from 5 to 9/s over 0-13 min and then leveled, as
      the rate of fall in [Ca2+] continued to increase and peak force decreased.
      Increasing the rate of fall in [Ca2+] increased the rate of relaxation, until a
      rate-limiting step was reached at approximately 9/s at 10 degrees C. At 20
      degrees C, incubation with EGTA-AM produced a linear approximately twofold
      increase in the rate of fall in twitch [Ca2+] without affecting the rate of
      relaxation (27/s). Ca2+ dissociated from the regulatory sites of purified
      troponin (Tn) at approximately 8/s at 10 degrees C and at 23/s at 20 degrees C.
      When the duration of the Ca2+ transient was decreased by EGTA or increased by
      partial inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase, twitch force
      increased linearly with Ca2+ transient duration. Thus the duration of the Ca2+
      transient is a primary determinant of twitch force and, whereas the rate of fall
      in [Ca2+] is rate limiting for relaxation at 10 degrees C, Ca2+ dissociation from
      Tn may be rate limiting at 20 degrees C.

PMID- 9176133
TI  - Gap junctional units are functionally expressed before first cleavage in the
      early ascidian embryo.
AB  - Manually apposed ascidian zygotes established electrical communication within 50
      min of fertilization and before cytokinesis. Junctional conductance between
      zygotes was 14.5 +/- 2.9 nS (n = 7), similar to that previously reported for
      ascidian two-cell-stage blastomeres, suggesting that zygotes and blastomeres
      express an equivalent number of gap junctional half-channels. Because puromycin
      at 400 microM does not inhibit the functional expression of these half-channels,
      they appear to be of maternal origin and their activation does not require
      protein synthesis. Loading zygotes with 500 mM ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid or exposing zygotes to 10 microM of
      the calcium ionophore A-23187 shows that these half-channels are regulated by
      intracellular calcium, consistent with the behavior of these channels in adult
      tissues. The results show that gap junctional units are expressed in the ascidian
      at the zygote stage.

PMID- 9176134
TI  - Acute metabolic acidosis inhibits the induction of osteoblastic egr-1 and type 1
      collagen.
AB  - Metabolic acidosis induces net calcium efflux from bone through a decrease in
      osteoblastic formation and an increase in osteoclastic resorption. We tested the
      hypothesis that changes in external pH would alter the expression of genes
      critical to the function of mouse calvarial bone cells, predominantly
      osteoblasts. Cells were cultured in physiologically neutral pH medium until
      confluent and then stimulated with fresh medium at either neutral or acidic pH.
      Among a group of immediate early response genes, including egr-1, junB, c-jun,
      junD, and c-fos, only egr-1 stimulation was modulated by changes in medium pH. At
      pH 7.4, RNA for egr-1 was stimulated approximately 10- to 30-fold, 40 min after
      medium change. A progressive decrease in pH to 6.8 led to a parallel reduction in
      egr-1 stimulation, and an increase in pH to 7.6 led to an increase in egr-1
      stimulation. The protein synthesis inhibitor cycloheximide led to a
      superinduction of egr-1 with preservation of the pH dependency of expression.
      Osteoblasts synthesize collagen, which is subsequently mineralized. RNA for type
      1 collagen was stimulated approximately three- to fivefold, 40 min after medium
      change. Again the stimulation was inhibited by acidosis and increased by
      alkalosis. Cycloheximide abolished the pH dependency of expression. These results
      suggest that small changes in external pH have a significant effect on the
      expression of certain genes important for osteoblastic function.

PMID- 9176135
TI  - Anion exchanger AE1 as a candidate pathway for taurine transport in rat
      erythrocytes.
AB  - Taurine has been shown to act as an osmolyte during the regulatory volume
      decrease process in a variety of cell types. The nature of the taurine efflux
      carrier is thought to consist of a diffusional pathway with pharmacological
      properties similar to a chloride channel or through an anion exchanger. We
      propose that taurine is a substrate of the anion exchanger AE1, also called band
      3. Experiments were performed in rat-erythrocytes, which express large amounts of
      band 3. Taurine uptake and efflux transport experiments were determined in the
      presence of inhibitors of anion carriers and chloride channels. Both taurine
      uptake and efflux were inhibited by band 3 inhibitors 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid (DIDS), 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS),
      niflumic acid, or furosemide. Moreover, DIDS competes with taurine at a common
      binding site in the uptake process. Specific inhibitors of the electroneutral
      cotransport as well as inhibitors of the chloride channels were ineffective in
      blocking taurine transport. Thus we suggest that band 3 may be the protein
      responsible for taurine transport in rat erythrocytes.

PMID- 9176136
TI  - Modulation of skeletal muscle Ca2(+)-release channel activity by sphingosine.
AB  - The effect of D-erythro-C18-sphingosine (sphingosine) and related compounds on
      the Ca(2+)-release channel (ryanodine binding protein) was examined on rabbit
      skeletal muscle membranes, on the purified ryanodine binding protein, and on the
      channel reconstituted into planar lipid bilayers. Sphingosine inhibited
      [3H]ryanodine binding to sarcoplasmic reticulum (SR) membranes in a dose
      dependent manner similar to published results (R. A. Sabbadini, R. Betto, A.
      Teresi, G. Fachechi-Cassano, and G. Salviati. J. Biol. Chem. 267: 15475-15484,
      1992). The sphingolipid also inhibited [3H]ryanodine binding to the purified
      ryanodine binding protein. Our results demonstrate that the inhibition of
      [3H]ryanodine binding by sphingosine is due to an increased rate of dissociation
      of bound [3H]ryanodine from SR membranes and a decreased rate of association of
      [3H]ryanodine to the high-affinity site. Unlike other modulators of the Ca(2+)
      release channel, sphingosine can remove bound [3H]ryanodine from the high
      affinity site within minutes. Sphingosine increased the rate of dissociation of
      [3H]ryanodine bound to a solubilized proteolytic fragment derived from the
      carboxy terminus of the ryanodine binding protein (cleavage at Arg4475).
      Sphingosine also inhibited the activity of the Ca(2+)-release channel
      incorporated into planar lipid bilayers. Taken together, the data provide
      evidence for a direct effect of sphingosine on the Ca(2+)-release channel.
      Sphingosine is a noncompetitive inhibitor at the high-affinity ryanodine binding
      site, and it interacts with a site between Arg4475 and the carboxy terminus of
      the Ca(2+)-release channel.

PMID- 9176137
TI  - A carboxy-terminal peptide of the alpha 1-subunit of the dihydropyridine receptor
      inhibits Ca(2+)-release channels.
AB  - Excitation-contraction coupling in skeletal muscle is thought to involve a
      physical interaction between the alpha 1-subunit of the dihydropyridine receptor
      (DHPR) and the sarcoplasmic reticulum (SR) Ca(2+)-release channel (also known as
      the ryanodine receptor). Considerable evidence has accumulated to suggest that
      the cytoplasmic loop between domains II and III of the DHPR alpha 1-subunit is at
      least partially responsible for this interaction. Other parts of this subunit or
      other subunits may, however, contribute to the functional and/or structural
      coupling between these two proteins. A synthetic peptide corresponding to a
      conserved sequence located between amino acids 1487 and 1506 in the carboxy
      terminus of the alpha 1-subunit inhibits both [3H]ryanodine binding to skeletal
      and cardiac SR membranes and the activity of skeletal SR Ca(2+)-release channels
      reconstituted into planar lipid bilayers. A second, multiantigenic peptide
      synthesized to correspond to the same sequence inhibits both binding and channel
      activity at lower concentrations than the linear peptide. These peptides slow the
      rate at which [3H]ryanodine binds to its high-affinity binding site and decrease
      the rate at which [3H]ryanodine dissociates from this site. A third polypeptide
      synthesized in Escherichia coli and corresponding to amino acids 1381-1627 and
      encompassing the above sequence has similar effects. This portion of the alpha 1
      subunit of the transverse tubule DHPR is therefore a candidate for contributing
      to the interaction of this protein with the Ca(2+)-release channel.

PMID- 9176138
TI  - Noncoordinate regulation of epithelial Na channel and Na pump subunit mRNAs in
      kidney and colon by aldosterone.
AB  - Distal colon and renal cortical collecting ducts are major effectors of
      aldosterone-dependent Na homeostasis. Na is absorbed by entry through an apical
      amiloride-sensitive Na channel and extruded by Na-K-ATPase at the basolateral
      membrane. Using a ribonuclease protection assay, we studied, in vivo, aldosterone
      regulation of alpha-, beta-, gamma-subunits of the rat epithelial Na channel
      (rENaC) and alpha 1- and beta 1-subunits of Na-K-ATPase. In the kidney, Na-K
      ATPase mRNAs were also assayed over discrete tubular segments by in situ
      hybridization. In rat colon, all three rENaC mRNAs were decreased by
      adrenalectomy, with a major effect on beta- and gamma-subunits, and were restored
      with 7 days, but not 2 days, of aldosterone treatment; in the kidney, however,
      only alpha-transcripts varied. Na-K-ATPase alpha 1- and beta 1-subunit mRNAs in
      both organs were not (in the case of the beta 1-subunit) or were mildly (in the
      case of the alpha 1-subunit) affected after adrenalectomy. Our conclusions are as
      follows: 1) Transcripts of rENaC and Na-K-ATPase subunits are not coordinately
      regulated by aldosterone in vivo; i.e., modulation involves mainly the Na
      channel, not Na-K-ATPase; the effect is not of comparable magnitude on each
      subunit mRNA and differs between tissues. 2) The delay of the aldosterone effect
      on transcripts is much longer than that required to restore normal Na transport
      in adrenalectomized rats, indicating that rENaC and Na-K-ATPase subunit
      transcript levels may depend on unidentified early aldosterone-induced proteins.

PMID- 9176139
TI  - ET-1 cooperates with EGF to induce mitogenesis via a PTX-sensitive pathway in
      airway smooth muscle cells.
AB  - We have examined the mitogenic effect of endothelin-1 (ET-1) alone or in
      combination with epidermal growth factor (EGF) in cultured airway smooth muscle
      cells (ASM) from guinea pig. ET-1 showed a weak mitogenic activity compared with
      the effect of EGF. However, when ET-1 and EGF were applied simultaneously, ET-1
      synergistically enhanced the mitogenic activity of EGF. Neither inhibition of
      phospholipase C-beta nor depletion of protein kinase C affected this synergism.
      On the other hand, pertussis toxin (PTX), a Gi protein inhibitor, abolished the
      synergistic effect of ET-1 on EGF-induced mitogenesis. ET-1 induced a transient
      mitogen-activated protein (MAP) kinase activation peaking at 5 min. In contrast,
      EGF induced a stronger signal that was maintained for up to 20 min. However,
      concomitant stimulation of ASM with ET-1 and EGF caused an enhanced MAP kinase
      activation compared with EGF alone. Moreover, PTX abolished the enhanced MAP
      kinase activation observed in this condition. These results indicate that ET-1
      can interact with an EGF-induced mitogenic axis through the Gi protein-dependent
      pathway, which is distinct from its direct mitogenic pathway.

PMID- 9176140
TI  - Proteoglycan synthesis in the intervertebral disk nucleus: the role of
      extracellular osmolality.
AB  - Proteoglycans, through their polyelectrolyte properties, regulate the ionic
      composition and hence the osmotic pressure of the extracellular matrix. We
      measured the change in [35S]sulfate incorporation, a marker of proteoglycan
      synthesis, in explants of bovine nucleus pulposus. During incubation, nucleus
      slices swelled 200% and proteoglycans leached from the matrix, so that
      extracellular osmolality fell from 420-450 to approximately 300 mosmol/kg H2O.
      When in vivo extracellular osmolality was maintained either by adding 80 mM NaCl
      or 150 mM sucrose to the swollen tissue or by preventing swelling, synthesis
      rates were 260-280% greater than in swollen tissue. Synthesis rates also
      increased 200% in cells isolated from the nucleus pulposus by enzyme digestion
      when medium osmolality was raised from 280 to 430 mosmol/ kgH2O by sucrose
      addition. The cells, either in the tissue or isolated from it, swelled by more
      than 20% as osmolality fell from 430 to 280 mosmol/kgH2O and showed little
      regulatory volume decrease over 150 min. Synthesis rates thus appear to be
      regulated by extracellular osmolality rather than by the macromolecular
      composition of the matrix and correlated well with measured changes in cell
      volume.

PMID- 9176141
TI  - Glutathione content of V79 cells in two- or three-dimensional culture.
AB  - The cellular glutathione (GSH) content of two- and three-dimensional cell
      cultures of V79 hamster lung cells has been studied. As previously described,
      cells in monolayer cultures show a decrease in GSH when they reach the confluent
      state. Three-dimensional cell cultures (multicell spheroids) allow a smoother
      transition from the initial proliferating to the nonproliferating status, and
      they show a central area of necrosis when a certain diameter is reached. Cellular
      GSH content in spheroids is variable throughout the culturing period: 1) GSH
      content (expressed per mg protein) is lower in spheroids with central necrotic
      areas than in smaller spheroids without necrosis, and 2) results expressed per
      cell number show a sharp increase around the diameter where necrosis appears.
      Once a relatively large necrotic area has been established, GSH decreases again
      to approximately the prenecrotic level. Interestingly, this GSH "peak" is not
      dependent on the time in culture but on the spheroid size. Acute hypoxia occurs
      in central areas of spheroids at a much higher size range than those described
      herein. Thus we suggest a combination of factors, which may include oxidative
      stress among others, as the explanation for these cellular GSH variations.

PMID- 9176142
TI  - Phenotypic characterization of an intestinal subepithelial myofibroblast cell
      line.
AB  - Subepithelial myofibroblasts are located at the interface between the epithelium
      and lamina propria in most mucosal tissues. Their biological functions are
      largely unknown because a long-term cell culture model for these cells has not
      been available. In this report, we define the phenotypic properties of a human
      colonic cell line (18Co) that exhibits most of the known characteristics of
      intestinal subepithelial myofibroblasts in situ. These characteristics include 1)
      a cell shape that can be reversibly interconverted between a flattened discoid
      and stellate morphology, 2) intracellular organelles reminiscent of
      myofibroblasts and smooth muscle cells in situ, 3) expression of alpha-smooth
      muscle actin, 4) plasma membrane receptors for endothelins and natriuretic
      peptides, and 5) regulation of epithelial sensitivity to calcium-dependent
      secretagogues by paracrine secretion of prostaglandins. 18Co cells provide an
      exploitable model to begin defining the physiological and pathophysiological
      functions of intestinal subepithelial myofibroblasts at the molecular level.

PMID- 9176143
TI  - Complexity of the outward K+ current of the rat megakaryocyte.
AB  - Megakaryocytes isolated from rat bone marrow express a voltage-dependent, outward
      K+ current with complex kinetics of activation and inactivation. We found that
      this current could be separated into at least two components based on
      differential responses to K+ channel blockers. One component, which exhibited
      features of the "transient" or "A-type" K+ current of excitable cells, was more
      strongly blocked by 4-aminopyridine (4-AP) than by tetrabutylammonium (TBA). This
      current, which we designated as "4-AP-sensitive" current, activated rapidly at
      potentials more positive than -40 mV and subsequently underwent rapid voltage
      dependent inactivation. A separate current that activated slowly was blocked much
      more effectively by TBA than by 4-AP. This "TBA-sensitive" component, which
      resembled a typical delayed rectifier current, was much more resistant to voltage
      dependent inactivation. The relative contribution of each of these components
      varied from cell to cell. The effect of charybdotoxin was similar to that of 4
      AP. Our data indicate that the voltage-dependent K+ current of resting
      megakaryocytes is more complex than heretofore believed and support the emerging
      concept that megakaryocytes possess intricate electrophysiological properties.

PMID- 9176145
TI  - Induction of human endothelial cell apoptosis requires both heat shock and
      oxidative stress responses.
AB  - Endothelial cell (EC) death may play an important role in the development of
      increased vascular permeability and capillary leak syndrome during systemic
      inflammatory response syndrome. However, the mode of EC death and the mechanisms
      involved remain unclear. In this study we employed the proinflammatory mediators
      lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha), the
      chemical reagent sodium arsenite, and heat shock to trigger the stress gene
      responses. Human ECs were used as surrogates of the microvasculature to test the
      hypothesis that the induction of the heat shock response and the oxidative stress
      response might combine to induce apoptosis rather than necrosis in human ECs.
      Sodium arsenite at 80-320 microM, which induced heat shock protein 72 (HSP72)
      expression and reactive oxygen intermediate (ROI) generation in ECs, resulted in
      EC apoptosis. TNF-alpha alone (5-75 ng/ml) increased EC ROI generation but did
      not induce EC apoptosis. Heat shock alone (42 degrees C, 45 min) or sodium
      arsenite (40 microM) alone, each of which induced HSP72 expression, did not
      result in EC apoptosis. However, the combination of TNF-alpha with heat shock or
      40 microM sodium arsenite led to EC apoptosis as HSP72 expression and ROI were
      induced. Furthermore, sodium arsenite (80 microM) in the presence of antioxidants
      failed to induce EC apoptosis. Apoptotic ECs also exhibited functional
      disturbances as represented by the depression of intercellular adhesion molecule
      1 expression as well as the disruption of EC monolayer integrity. These results
      indicate that the simultaneous induction of a heat shock response and an
      oxidative stress response is responsible for human EC apoptosis.

PMID- 9176144
TI  - NH2-terminal-inserted myosin II heavy chain is expressed in smooth muscle of
      small muscular arteries.
AB  - We demonstrate, using reverse transcriptase-polymerase chain reaction, that,
      whereas abdominal aorta from rabbit consists almost entirely of myosin heavy
      chain (MHC) mRNA with no insert at the 5'-terminal coding region, the
      distributing arteries (femoral and saphenous) begin to show MHC mRNA with the 21
      nucleotide insert that encodes seven amino acids in the ATP-binding region
      located in the myosin head. The femoral/iliac artery contains > 50% inserted
      mRNA, whereas the more distal saphenous artery contains > 80% inserted mRNA. This
      insert is also present in the smooth muscle from rat tail artery but is absent in
      the smooth muscle from rat aorta. The actin-activated ATPase activity of myosin
      from the rabbit femoral/saphenous artery is 1.7-fold higher than that of the
      myosin from the aorta. A concomitant increase (about twofold) in the maximum
      shortening velocity of the saphenous artery, compared with that of the aorta,
      indicates that the preponderance of the inserted myosin is associated with both
      an increase in the actin-activated ATPase activity and a larger maximum velocity
      of shortening. Furthermore, analysis of the 17-kDa essential light chain from the
      aorta reveals near equal quantities of the 17-kDa light chain isoforms a and b,
      whereas the myosin from the femoral/ saphenous artery contains predominantly the
      17-kDa light chain a isoform. Together, these data indicate that the smooth
      muscle cells from the small distributing arteries are similar to those of
      visceral smooth muscle with respect to the expression of myosin isoforms, actin
      activated myosin ATPase activity and contractility.

PMID- 9176146
TI  - Glucose transport by isolated plasma membranes of the bovine blood-brain barrier.
AB  - Luminal and abluminal endothelial plasma membrane vesicles were isolated from
      bovine cerebral microvessels, the site of the blood-brain barrier. Glucose
      transport across each membrane was measured using a rapid-filtration technique.
      Glucose transport into luminal vesicles occurred by a stereospecific energy
      independent transporter [Michaelis-Menten constant (K(m)) = 10.3 +/- 2.8 (SE) mM
      and maximal velocity (Vmax) = 8.6 +/- 2.0 nmol.mg protein(-1).min-1]. Kinetic
      analysis of abluminal vesicles also showed a transport system with
      characteristics similar to the luminal transporter (K(m) = 12.5 +/- 2.3 mM and
      Vmax = 10.0 +/- 1.0 nmol.mg protein-1.min-1). These functional, facilitative
      glucose transporters were symmetrically distributed between the luminal and
      abluminal membrane domains, providing a mechanism for glucose movement between
      blood and brain. The studies also revealed a Na-dependent transporter on the
      abluminal membrane with a higher affinity and lower capacity than the
      facilitative transporters (K(m) = 130 +/- 20 microM and Vmax = 1.59 +/- 0.44
      nmol.mg protein-1.min-1. The abluminal Na-dependent glucose transporter is in a
      position to transport glucose from the brain extracellular fluid into the
      endothelial cells of the blood-brain barrier. The functional significance of its
      presence there remains to be determined.

PMID- 9176147
TI  - Angiotensin II activates the beta 1 isoform of phospholipase C in vascular smooth
      muscle cells.
AB  - Vascular smooth muscle cells (VSMC) contribute to the pathophysiology of
      hypertension through cell growth and contraction, and phospholipase C (PLC) is a
      critical effector enzyme in growth factor and vasoconstrictor signaling. There is
      indirect evidence that angiotensin II (ANG II) receptors are linked to the PLC
      beta isoform signaling pathways. However, recent studies suggest that PLC-beta
      isoforms may not be expressed in VSMC. Our data demonstrate that in human aortic
      VSMC, PLC-beta 1 and PLC-gamma 1 proteins were detected by immunoblot analysis,
      and PLC-beta 1 mRNA was identified by reverse transcriptase-polymerase chain
      reaction in rat aortic VSMC. Incubation of permeabilized VSMC with anti-PLC-beta
      1 or anti-Gq alpha antibodies inhibited ANG II-dependent inositol polyphosphate
      (IP) formation, while anti-PLC-gamma 1 antibodies did not inhibit ANG II
      regulated IP formation. Conversely, anti-PLC-gamma 1 antibodies completely
      abolished platelet-derived growth factor (PDGF)-dependent IP generation, whereas
      anti-PLC-beta 1 antibodies had no effect on PDGF-induced PLC activation.
      Inhibition of tyrosine phosphorylation with genistein or herbimycin A did not
      diminish ANG II-stimulated IP formation or cytosolic free Ca2+ concentration
      transients, thereby confirming that ANG II signals via a PLC-gamma 1-independent
      mechanism. In summary, PLC-beta 1 and PLC-gamma 1 are expressed in human aortic
      VSMC, and PLC-beta 1 is the isoform that is critical for ANG II-regulated PLC
      signaling in these cells.

PMID- 9176148
TI  - In vivo brain phosphocreatine and ATP regulation in mice fed a creatine analog.
AB  - Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells
      with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a
      competitive inhibitor of creatine transport, was used to study the hypothesis
      that the creatine-CK-phosphocreatine (PCr) system is important in regulating
      brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations
      were measured in vivo with 31P nuclear magnetic resonance spectroscopy during
      energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane
      anesthetized mice fed GPA, creatine, or standard chow (controls). Brain
      phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP)
      concentrations were equal. The phosphagen-to-NTP ratio was lower than in
      controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK
      activity that was biochemically measured was doubled. During seizures, CK
      catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed
      mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen
      and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast
      to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia
      and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or
      adaptive changes in ATP metabolism stabilize brain ATP and enhance survival
      during hypoxia in mice.

PMID- 9176149
TI  - Submandibular enzymatic vasoconstrictor increases DNA and phosphoinositol
      synthesis by mesenchymal cells.
AB  - Submandibular enzymatic vasoconstrictor (SEV, rK9) induces vascular contraction
      and platelet aggregation by a mechanism requiring intact enzymatic activity. On
      the basis of a published report demonstrating growth-promoting enzymatic activity
      in an extract of the rat submandibular gland, we hypothesized that SEV would
      affect DNA synthesis. Recombinant SEV (rSEV), expressed in a baculovirus system,
      increased DNA synthesis 3- to 25-fold in Chinese hamster lung (CCL39) fibroblasts
      and in rabbit and rat vascular smooth muscle cells in a dose-dependent manner
      dose eliciting 50% of maximal response: 0.1-1 nM); this effect was inhibited by
      pertussis toxin (PTX). Inactive rSEV failed to enhance DNA synthesis. In CCL39
      fibroblasts, rSEV increased total phosphoinositol (PI) formation (6- to 10-fold
      at 10 nM), which was inhibited 49% by PTX; it was also partially inhibited by the
      tyrosine kinase inhibitor genistein (33%) but was not affected by the protein
      kinase C inhibitor bisindolylmaleimide. These results show that rSEV increases
      DNA synthesis and PI formation in mesenchymal cells in a dose- and enzymatic
      activity-dependent manner through a pathway partially mediated by a PTX-sensitive
      G protein. Thus SEV can induce growth-associated responses, perhaps through a
      protease-activated receptor mechanism.

PMID- 9176150
TI  - Tension response of the cardiotonic agent (+)-EMD-57033 at the single cell level.
AB  - The effects of the Ca sensitizer (+)-EMD-57033 were tested on single chemically
      skinned cells isolated from rat ventricle. The present study demonstrates that
      (+)-EMD-57033 (10 microM) increased maximal force by 20% (at pCa 4.5) and
      myofilament Ca sensitivity by 0.2 pCa unit. However, the force-length dependency
      was not affected by the addition of (+)-EMD-57033, since similar Ca-sensitizing
      effects occurred at different sarcomere lengths. Consequently, the Ca-sensitizing
      effect of the drug and of the sarcomere length might be additive. Cross-bridge
      kinetics were also investigated in the presence of the thiadiazinone derivative.
      (+)-EMD-57033 induced marked increases in the rate of tension redevelopment (ktr)
      after brief slack release/restretch, particularly at low Ca concentrations. These
      results suggest that the Ca-sensitizing effects of (+)-EMD-57033 are due, at
      least in part, to an increased number of attached cross bridges during one cyclo.
      This observation, together with the increase in peak force, is discussed in
      relation to the reduction in energy cost induced by such Ca-sensitizing agents.

PMID- 9176151
TI  - Small GTP-binding protein, Rab6, is associated with secretory granules in atrial
      myocytes.
AB  - Rab proteins, a subfamily of small GTP-binding proteins, have been shown to play
      key roles in regulation of vesicular traffic in eukaryotic cells. In this study,
      we have intended to identify, the atrial granule-associated Rab proteins that
      seem to be required for formation or intracellular transport of the granules.
      Atrial granules contained at least four small GTP-binding proteins, and we have
      demonstrated by biochemical analysis that one of the small GTP-binding proteins
      associated with the atrial granules is a Rab6 protein (Rab6p). Rab6p was also
      detected in highly purified zymogen granules of pancreatic exocrine gland.
      Immunogold electron microscopy performed on ultrathin cryosections of rat auricle
      revealed that Rab6p was associated with the atrial granule membranes. Association
      of Rab6p with the atrial granule membranes was also confirmed by immunodiffusion
      electron microscopy in agarose-embedded atrial granules. These data indicate that
      Rab6p is associated with the atrial granules and that it might function in the
      intracellular traffic of the secretory granules in the atrial myocytes.

PMID- 9176152
TI  - Extracellular ATP regulates transcervical permeability by modulating two distinct
      paracellular pathways.
AB  - Extracellular ATP stimulates a biphasic change in transepithelial electrical
      resistance (RTE) across cultures of human cervical epithelial cells: an acute
      decrease (phase I), followed by a delayed increase in resistance (phase II). The
      objective of this study was to determine the contributions of changes in the
      lateral intercellular space resistance (RLIS) and the tight junctional resistance
      (RTJ) to the changes in RTE. Phase I and phase II effects were uncoupled by
      treatment with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)
      acetoxymethyl ester, which blocks the ATP-induced increases in cytosolic Ca2+ and
      abolishes phase I. BAPTA-loaded cells differed from control cells in that 1)
      phase I began when ATP was added, in contrast to a delay of 1.5-3.5 min in phase
      II, 2) phase I decreases in RLIS followed a simple exponential pattern, in
      contrast to the complex kinetics of phase II, and 3) the magnitude of phase II
      varied between 20 and 100% for increases of RTJ in day 2-6 cultures; the phase I
      decrease of 50% in RLIS was unrelated to different experimental conditions. These
      results indicate that phase I and phase II are induced simultaneously and
      independently by ATP, and they contribute to the total changes in RTE. We
      conclude that ATP regulation of RLIS and RTJ may be important mechanisms of
      modulating cervical mucus production in vivo.

PMID- 9176153
TI  - Extracellular ATP modulates [Ca2+]i in retinoic acid-treated embryonic
      chondrocytes.
AB  - When treated with low doses of retinoic acid (RA), cephalic chondrocytes of the
      chick embryonic sternum mature and express phenotypic characteristics of
      postmitotic hypertrophic cells. In concert with these maturation-dependent
      changes, cells release adenine nucleotides into the culture medium. To ascertain
      if these compounds modulate chondrocyte function, we challenged chondrocytes with
      nucleotides and measured one determinant of the signal transduction pathway,
      intracellular Ca2+ concentration ([Ca2+]i). In the presence of micromolar
      concentrations of ATP, there was a dose-dependent elevation in chondrocyte
      [Ca2+]i; ADP caused a small but significant rise in the peak [Ca2+]i response. We
      found that the change in the [Ca2+]i response is linked to retinoid-dependent
      maturation of chondrocytes. Thus the [Ca2+]i rise was dependent on the RA
      concentration and treatment time. Immature caudal chondrocytes, cells that were
      not affected by RA, were used as control cells for this study. When treated with
      ATP, these cells did not exhibit a [Ca2+]i response. Although the purinergic
      subtype receptor was not characterized, the observation that cells responded to
      ATP and ADP but were refractory to AMP and adenosine suggested that P2
      purinoceptors were expressed by chondrocytes. Because, during the same culture
      period, chondrocytes exhibited many of the unique characteristics of the
      terminally differentiated cell, the acquisition of purinergic receptors
      represents a new feature associated with expression of the mature phenotype.
      Finally, to ascertain if the ATP-dependent response was due to release of Ca2+
      from intracellular stores, cells were treated with thapsigargin. Since this
      compound significantly reduced the [Ca2+]i signal, we concluded that the ATP
      response is mediated by release of cation, from the endoplasmic reticulum.

PMID- 9176154
TI  - Quantification of ion transport in perfused rat heart: 133Cs+ as an NMR active K+
      analog.
AB  - Proper ion balance between intra- and extracellular compartments is necessary for
      normal physiological function. Conversely, alterations in membrane ion transport
      occur in numerous pathological states. As a noninvasive, nondestructive
      spectroscopic technique, nuclear magnetic resonance (NMR) offers a powerful
      approach to the study of ion balance in intact biological systems. Unfortunately,
      rare NMR active nuclides that are isotopes of the 100% naturally abundant 23Na+
      and 39K+ are not available for tracer kinetic studies of Na1 and K+ transport.
      However, Cs is a biologically active analog of K+, and the 100% naturally
      abundant NMR active 133Cs+ nuclide can be employed to examine K+ transport
      (Davis, D. G., E. Murphy, and R. E. London. Biochemistry 27: 3547-3551, 1988).
      The distinguishing feature of 133Cs+ is that it naturally gives two separate well
      resolved NMR resonances for intra- and extra-cellular 133Cs+, permitting study of
      the time course changes of either of these compartments independent of the other.
      In this report, the experimental procedures and compartmental modeling formalism
      are developed that allow quantitative analysis of Cs+ membrane transport in the
      perfused rat heart. Intracellular 133Cs+ is shown to be 100% visible by solution
      state NMR methods and its influx transport to be markedly inhibited by ouabain, a
      confirmation of findings previously reported by others. Intracellular 133Cs+ spin
      lattice and spin-spin relaxation times at 7 T were determined to be 2.1 +/- 0.3
      (SD)s (n = 8) and 0.065 +/- 0.007 (SD) s (n = 8), respectively, for T1 and T2.
      The rate constant for Na(+)-K(+)-ATPase pump dominated intracellular influx was
      measured to be 0.25 +/- 0.07 (SD) min-1 (n = 27) and that for efflux 0.005 +/-
      0.001 (SD) min-1 (n = 14). The rate constant for 133Cs+ equilibration in the
      extracellular space at supraphysiological perfusate flow rate (20 ml/min) was
      found to be 4.6 +/- 0.9 (SD) min-1 (n = 20). Thus extracellular diffusion
      limitations do not dominate the 133Cs+ transport measurements.

PMID- 9176155
TI  - Inhibition of ion transport in septic rat heart: 133Cs+ as an NMR active K+
      analog.
AB  - Sepsis, the systemic response to severe infection, and the resulting multiorgan
      failure it induces are major contributors to intensive care unit morbidity and
      mortality. A number of abnormalities in ion transport processes and intracellular
      free Na+ ([Na+]i) and K+ ([K+]i) concentrations have been reported to occur
      during sepsis/endotoxemia. An effect of sepsis on the NA(+)-K(+)-ATPase may be an
      important contribution to changes in intracellular ion balance and the resultant
      pathophysiology of the disorder. The purpose of this study was to examine the
      effect of sepsis on the Na(+)-K(+)-ATPase in the isolated perfused rat heart
      using 133Cs+ nuclear magnetic resonance (NMR). Cs+ is a K+ analog, and 133Cs-NMR
      offers the opportunity to examine Na(+)-K(+)-ATPase activity in the intact organ
      via tracer kinetics. Sepsis was induced in halothane-anesthetized male Sprague
      Dawley rats using the cecal ligation and perforation (CLP) model. Twenty-four to
      thirty-six hours after surgery, hearts from CLP or sham-operated rats were
      perfused with Krebs-Henseleit buffer containing 1.25 mM Cs+. The influx rate
      constant for Cs+ was decreased by 24% in septic rat hearts, i.e., 0.25 +/- 0.08
      (SD) min 1 for controls and 0.19 +/- 0.04 (SD) min-1 for septic animals (P =
      0.003). There was no difference for Cs+ efflux [0.005 +/- 0.001 (SD) min-1 for
      controls and 0.005 +/- 0.002 (SD) min-1 for septic animals; P = 0.8]. These
      results are consistent with an inhibition of the Na(+)-K(+)-ATPase pump during
      sepsis/endotoxemia. A decrease in the activity of the Na(+)-K(+)-ATPase pump may
      be responsible for or contribute to the changes in [Na+]i and [K+]i during the
      disorder.

PMID- 9176156
TI  - Altered pHi regulation in 3T3/CFTR clones and their chemotherapeutic drug
      selected derivatives.
AB  - Recently (L. Y. Wei, M. J. Stutts, M. M. Hoffman, and P. D. Roepe. Biophys. J.
      69: 883-895, 1996), 3T3 cells overexpressing the cystic fibrosis transmembrane
      conductance regulator (CFTR) were found to exhibit chemotherapeutic drug
      resistance and other traits of multidrug resistant (MDR) cells. In the present
      work, NIH 3T3/CFTR clones were selected with either doxorubicin or vincristine in
      incremental fashion to generate series of stable MDR cell lines that exhibit
      increasing levels of drug resistance. Thus C3D6 (grown in the presence of 600 nM
      doxorubicin) was selected from C3D4 (grown in the presence of 400 nM
      doxorubicin), which was selected from C3D1 (grown in the presence of 100 nM
      doxorubicin), which was in turn selected from the original 3T3/CFTR clone C3 (M.
      J. Stutts, S. E. Gabriel, J. C. Olsen, J. T. Gatzy, T. L. O'Connell, E. M. Price,
      and R. C. Boucher. J. Biol. Chem. 268: 20653-20658, 1993), which was not grown in
      the presence of chemotherapeutic drug. A similar series was generated via
      selection with vincristine. In both series, as well as series derived from a
      different CFTR clone, initial low-level drug selection increases CFTR expression
      without promoting MDR 1 or multidrug resistance-associated protein expression. On
      continued selection at higher drug concentrations, CFTR mRNA levels decrease
      while MDR 1 mRNA levels concomitantly increase. At each incremental step of
      selection, intracellular pH (pHi) increases (e.g., pHi of C3D6 > C3D4 > C3D1 >
      C3). Cl-/HCO3- exchange activity is significantly reduced in the drug-selected
      derivatives overexpressing MDR 1 but not the parental CFTR clones. The apparent
      set point of Na+/H+ exchange activity is significantly lower for the non-drug
      selected 3T3/CFTR clones, relative to controls, but it increases on initial
      selection with chemotherapeutic drug. Overexpression of MDR 1 in the higher-level
      selectants does not appear to further perturb apparent Na+/H+ exchange. These
      data further describe how CFTR and MDR proteins may affect pHi regulation.

PMID- 9176157
TI  - Cytoskeletal mechanics in confluent epithelial cells probed through integrins and
      E-cadherins.
AB  - Mechanical forces associated with the cytoskeleton (CSK) and transmitted to
      adjacent cells or to the extracellular matrix (ECM) influence cellular functions.
      We investigated the force transfer across cell-to-ECM and cell-to-cell
      connections using magnetic twisting cytometry. We probed the CSK through
      integrins and E-cadherins in confluent epithelial cell lines (MCF7). At high
      applied stress (> 10 dyn/cm2), stiffness (stress/strain) of the CSK coupled
      through integrins was greater than stiffness coupled through E-cadherins. The
      stiffness reduction after microfilament or microtubule disruption with
      cytochalasin D or colchicine was greater for integrins. At low applied stress,
      disruption of microfilaments had very little effect on stiffness probed through
      either receptor type, indicating a correspondingly small contribution of
      microfilaments to the CSK mechanics in these confluent cells. This differs from
      results in nonconfluent MCF7 cells and from predictions that are based on
      prestressed models in which tensile stresses presumably associated with the
      microfilaments are the origin of prestress and, in consequence, cell stiffness.
      In addition, there was substantial cell spreading on collagen I-coated dishes, in
      contrast to little spreading on dishes coated with E-cadherin antibody. This
      result, together with observations of a relatively high cell stiffness probed
      through integrins compared with the small stiffness probed through E-cadherins,
      suggests that mechanical force transmission might also be important in regulating
      cell spreading. We conclude that the degree of confluency may be associated with
      different mechanics and functions of the CSK network.

PMID- 9176158
TI  - Role of calcium and cross bridges in determining rate of force development in
      frog muscle fibers.
AB  - The influence of Ca2+ and force-generating cross bridges on the kinetics of force
      development was examined in skinned frog muscle fibers activated by photolytic
      release of Ca2+ from caged Ca2+ at 10 degrees C. Isometric force development was
      fit by a double exponential equation with rates of 44.4 s-1 (kc1) and 6.1 s-1
      (kc2); kc1 was not significantly different from the rate of force development
      observed in intact fibers. Maximum activation by caged Ca2+ from preexisting
      submaximal force produced rates of contraction similar to those observed with
      maximum activation from zero force. Decreasing the Ca2+ level to an extent that
      resulted in 50% of maximum force development produced an approximately sevenfold
      decrease in kc1 and no change in kc2. Partial extraction of troponin C reduced
      kc1 only slightly (by 16%), whereas decreasing the number of force-generating
      cross bridges by vanadate did not decrease kc1. Neither treatment altered kc2.
      Thus the rate of force development increases dramatically with increases in Ca2+
      level.

PMID- 9176159
TI  - A synthetic peptide derived from glycine-gated Cl- channel induces
      transepithelial Cl- and fluid secretion.
AB  - M2GlyR is a synthetic 23-amino acid peptide that mimics the second membrane
      spanning region of the alpha-subunit of the postsynaptic glycine receptor. This
      peptide has been shown to form an anion-selective channel in phospholipid
      bilayers. We have investigated the possibility that the peptide may incorporate
      into the apical membrane of secretory epithelia and induce the secretion of Cl-
      and water. We improved the solubility of this peptide by adding four lysine
      residues to the carboxy terminus, C-K4-M2GlyR, and assayed its channel-forming
      activity using a subculture of Madin-Darby canine kidney (MDCK) cells. The
      addition of 100 microM C-K4-M2GlyR to the apical surface of MDCK monolayers
      significantly increased short-circuit current (Ise), hyperpolarized
      transepithelial potential difference, and induced fluid secretion. The increase
      in Ise was inhibited by 100 microM bumetanide and by Cl- channel inhibitors. The
      effectiveness of the channel blockers followed the sequence niflumic acid > or =
      5-nitro-2-(3-phenylpropylamino)benzoate > diphenylamine-2-carboxylate (DPC) >
      glibenclamide. The effect of the peptide was not inhibited by 4.4'
      diisothiocyanostilbene-2-2'-disulfonic acid. Removing Cl from the bathing
      solutions also inhibited the effect of the peptide. The Cl- efflux pathway
      induced by C-K4-M2GlyR differs from the native pathway activated by the adenosine
      3',5'-cyclic monophosphate (cAMP) agonist, forskolin. First, intracellular cAMP
      levels were unaffected. Second, the concentration of DPC required to inhibit the
      effect of the peptide was much lower than that needed to block the forskolin
      response (100 microM vs. 3 mM). These results support the hypothesis that the
      synthetic peptide C-K4-M2GlyR can from Cl -selective channels in the apical
      membrane of secretory epithelial cells and can induce sustained transepithelial
      secretion of Cl- and fluid.

PMID- 9176160
TI  - ATP depletion alters myosin I beta cellular location in LLC-PK1 cells.
AB  - The brush border (BB) of the proximal tubule cell (PTC) requires dynamic membrane
      events for function. The actin cytoskeleton is necessary for structure and
      function in this region. ATP depletion disrupts both structure and function. In
      this report, myosin 1 beta location in LLC-PK1 cells was followed during ATP
      depletion and repletion using immunofluorescence and Western blot techniques.
      Myosin I beta colocalized with F-actin in the microvilli and cell periphery, but
      no colocalization was observed with stress fibers. ATP depletion increased the
      apical F-actin, and myosin I beta was colocalized there. In addition, after ATP
      depletion, myosin I beta was extracted less by Triton X-100. These changes were
      reversed after ATP repletion. Finally, immunofluorescence of kidney sections
      shows myosin I beta in the BB. These results place this motor in a dynamic region
      of the PTC where its actin and membrane binding domains can contribute to PTC
      function.

PMID- 9176162
TI  - Distinct effect of hypoxia on endothelial cell proliferation and cycling.
AB  - Endothelial cells (EC) occupy a strategic location in the vasculature as a
      barrier between the intravascular compartment and underlying tissues; as such,
      they are often exposed to stresses, such as decreases in ambient oxygen,
      diminished metabolic substrate, or changes in temperature, that could affect
      their ability to divide and proliferate. The present study characterizes cell
      counts, cell cycle distribution, and bromodeoxyuridine incorporation in pulmonary
      artery and aortic EC exposed to acute and/or chronic hypoxia and other cellular
      stresses. During hypoxia, EC division slows but does not arrest; progression
      through the G1-to-S transition point and/or progression from S to G2/M is altered
      with an increased percent of EC in S phase. These changes in EC cell cycle
      distribution with hypoxia are dependent on the origin of the EC as well as the
      ambient oxygen concentration; moreover, they are distinct from changes observed
      with elevated temperature or glucose deprivation. and differ from the quiescent
      pattern induced by serum deprivation or high-density confluence. These findings
      demonstrate that hypoxia exerts a distinct effect on the cell cycle distribution
      and proliferation of EC.

PMID- 9176161
TI  - Amino acid control of asparagine synthetase: relation to asparaginase resistance
      in human leukemia cells.
AB  - Complete amino acid deprivation in mammalian cells causes a significant
      enhancement in gene expression for a number of important cellular activities;
      among these is asparagine synthetase (AS). The data presented demonstrate that,
      in both nonleukemic (rat Fao hepatoma cells) and human leukemia cells (MOLT-4,
      NALL-1, and BALL-1), AS mRNA levels, protein content, and enzymatic activity are
      induced after incubation in an otherwise complete tissue culture medium that is
      deficient in a single amino acid or in medium that has been depleted of the amino
      acid asparagine by the addition of asparaginase. Complete amino acid deprivation
      results in a concerted increase in AS mRNA, protein, and enzymatic activity,
      which, in conjunction with previously published research, suggests that the
      mechanism of this cellular response involves transcriptional control of the AS
      gene. Asparaginase treatment is a standard component of acute lymphoblastic
      leukemia therapy for which the effectiveness is related to the inability of these
      cells to upregulate AS activity to a sufficient level. With regard to the
      asparaginase sensitivity of the three human leukemia cell lines, there was a
      trend toward an inverse relation to the degree of AS expression. Selection for
      asparaginase-resistant MOLT-4 sublines resulted in enhanced AS mRNA and protein
      content regardless of whether the cells had been selected by asparaginase
      treatment directly or asparagine was removed from the culture medium.
      Collectively, the data illustrate that further advances in asparaginase therapy
      will require additional knowledge of amino acid-dependent regulation of AS gene
      expression and, conversely, that asparaginase resistance represents a model
      system for investigating metabolite control in a clinically relevant setting.

PMID- 9176163
TI  - Temporal expression of PDGF receptors and PDGF regulatory effects on osteoblastic
      cells in mineralizing cultures.
AB  - Platelet-derived growth factor (PDGF) is mitogenic and chemotactic for
      osteoblastic cells in vitro. It is expressed during osseous wound healing and
      stimulates formation of new bone in vivo. PDGF stimulates cells by binding to
      specific cell surface receptors. The purpose of this study was to examine the
      effects of PDGF on osteoblastic proliferation and differentiation in long-term
      mineralizing cultures. Utilizing Northern blot analysis, we found that continuous
      PDGF treatment increased histone expression, indicative of enhanced
      proliferation, but suppressed osteoblast differentiation, demonstrated by
      inhibition of alkaline phosphatase, type I collagen, and osteocalcin expression.
      The inhibitory effect of PDGF on the differentiated function of osteoblasts was
      further established by findings that PDGF significantly inhibited nodule
      formation. The expression of PDGF receptors varied at different stages of
      culture. PDGF receptor mRNA expression increased when the cells had achieved a
      mature phenotype, during the stage of matrix maturation, and then decreased.
      However, as demonstrated by thymidine incorporation assays, the capacity of PDGF
      to stimulate DNA synthesis actually decreased during osteoblast maturation, as
      receptor expression increased. To investigate this apparent contradiction,
      tyrosyl phosphorylation and immunoblot assays were performed to assess changes in
      PDGF activation of their cognate receptors. The pattern of PDGF-induced tyrosyl
      phosphorylation remained relatively constant. This suggests that the diminished
      mitogenic activity of PDGF that occurs after osteoblast differentiation is
      regulated at a postreceptor level.

PMID- 9176164
TI  - Amino acids Val115-Ile126 of rat gastric H(+)-K(+)-ATPase confer high affinity
      for Sch-28080 to Na(+)-K(+)-ATPase.
AB  - Na(+)-K(+)-ATPase is inhibited by cardiac glycosides and is insensitive to Sch
      28080, an inhibitor of gastric H(+)-K(+)-ATPase. Gastric H(+)-K(+)-ATPase is not
      inhibited by cardiac glycosides. Both ouabain and, Sch-28080 binding are
      inhibited by K+, and it has been suggested that the inhibitors bind to
      corresponding regions on the alpha-subunit of each ion pump. For identification
      of regions of each pump that interact with the specific inhibitors, chimeric
      alpha-subunits consisting of selected regions from Na(+)-K(+)-ATPase and gastric
      H(+)-K(+)-ATPase have been prepared. One chimera (gM1/2) has been constructed
      from cDNA of the sheep alpha1-subunit of Na(+)-K(+)-ATPase by replacement of the
      last 12 amino acids of the first predicted transmembrane region (Ile99-Ile110)
      with corresponding amino acids from rat gastric H(+)-K(+)-ATPase. gM1/2 was
      expressed in yeast cells together with either the rat Na(+)-K(+)-ATPase beta 1
      subunit (NK beta 1) or rat gastric H(+)-K(+)-ATPase beta-subunit (HK beta).
      Western blots show that the expression level of the chimeric alpha-subunit was
      comparable to the Na(+)-K(+)-ATPase alpha 1. Ouabain binds with high affinity to
      gM1/2+NK beta 1 [ouabain binding affinity (Kd) = 9.5 nM] but not to gM1/2+HK
      beta. The Kd for ouabain binding to Na(+)-K(+)-ATPase was 7.8 nM. Na(+)-K(+)
      ATPase activity of gM1/2+NK beta 1 was inhibited both by ouabain and Sch-28080.
      The 50% inhibition concentration for Sch-28080 was 20-60 nM. Sch-28080 at 10
      microM did not inhibit Mg(2+)- and Pi-dependent ouabain binding to gM1/2+NK beta
      1. Ouabain (0.75 mM) inhibited palytoxin-induced K+ efflux from yeast cells
      expressing either gM1/2+NK beta 1 or gM1/2+NK beta, and Sch-28080 increased the
      palytoxin-induced K+ efflux from yeast cells expressing gM1/2+NK beta 1 or
      gM1/2+HK beta. These results implicate a small number of amino acids in the first
      transmembrane part of gastric H(+)-K(+)-ATPase as partial determinants of the
      sensitivity to Sch-28080. The data also suggest that ouabain and Sch-28080 do not
      bind to the same site on the chimera.

PMID- 9176165
TI  - Different interactions of cardiac and skeletal muscle ryanodine receptors with FK
      506 binding protein isoforms.
AB  - In the present study, we compare functional consequences of dissociation and
      reconstitution of binding proteins FKBP12 and FKBP12.6 with ryanodine receptors
      from cardiac (RyR2) and skeletal muscle (RyR1). The skeletal muscle RyR1 channel
      became activated on removal of endogenously bound FKBP12, consistent with
      previous reports. Both FKBP12 and FKBP12.6 rebind to FKBP-depleted RyR1 and
      restore its quiescent channel behavior by altering ligand sensitivity, as studied
      by single-channel recordings in planar lipid bilayers, and macroscopic behavior
      of the channels (ryanodine binding and net energized Ca2- uptake). By contrast,
      removal of FKBP12.6 from the cardiac RyR2 did not modulate the function of the
      channel using the same types of assays as for RyR1. FKBP12 or FKBP12.6 had no
      effect on channel activity of FKBP12.6-depleted cardiac RyR2, although FKBP12.6
      rebinds. Our studies reveal important differences between the two ryanodine
      receptor isoforms with respect to their functional interaction with FKBP12 and
      FKBP12.6.

PMID- 9176166
TI  - Eccentric contractions decrease glucose transporter transcription rate, mRNA, and
      protein in skeletal muscle.
AB  - We have recently shown that eccentric contractions (ECs; forced lengthening of
      active muscle) elicit a delayed decrease in glucose transporter (GLUT-4) protein
      content in rat skeletal muscle and a decrease in subsequent contraction
      stimulated glucose transport. Here, we investigate whether this decrease in total
      GLUT-4 protein after prior ECs is due to changes in GLUT-4 gene transcription
      rate and GLUT-4 mRNA level. Furthermore, the effect of prior ECs on sarcolemmal
      GLUT-4 protein content in plasma membrane (PM) vesicles isolated from contraction
      stimulated muscle was determined. Rat gastrocnemius muscle was electrically
      stimulated for ECs, and the contralateral muscle served, as unstimulated control
      (UC). Two days later, the total GLUT-4 protein content was decreased by 50% (P <
      0.05) and 32% (P < 0.05) in the white and red gastrocnemius muscle, respectively.
      Furthermore, the GLUT-4 mRNA concentration was decreased by 41% (P < 0.05) in
      both the white and red gastrocnemius muscle. Moreover, the GLUT-4 transcription
      rate, determined by nuclear run-on analysis, was decreased by 75% (P < 0.05) in
      mixed EC gastrocnemius muscle compared with UC muscle. PM vesicles were isolated
      from EC and UC muscle after 15 min of isometric contractions. The PM GLUT-4
      protein content was reduced by 51% (P < 0.05) in EC muscle compared with UC
      muscle. In conclusion, 2 days after ECs, the GLUT-4 transcription rate, GLUT-4
      mRNA, and GLUT-4 protein content were decreased in rat skeletal muscle. Moreover,
      the PM GLUT-4 protein content in contraction-stimulated muscle was decreased. We
      suggest that eccentric muscle contractions decrease muscle GLUT-4 transcription
      rate, resulting in a lower GLUT-4 protein content, which in turn decreases the
      number of GLUT-4 transporters translocated to the sarcolemma, ultimately leading
      to decreased contraction-induced muscle glucose transport.

PMID- 9176167
TI  - Multiple equilibria of cations with metabolites in muscle bioenergetics.
AB  - The multiple ionic forms of metabolites were evaluated at 37 degrees C for four
      reactions important in muscle contraction and recovery: 1) ATPase, 2) creatine
      kinase, 3) the Lohmann reaction, and 4) the Lohmann reaction reversed by coupling
      to glycogenolysis and glycolysis. Solution of the system of equations defining
      the multiple equilibria of the proton and cation complexes gives the
      concentration of each ionic form and a value for the proton stoichiometry for
      each reaction. The proton stoichiometric coefficients are unique for each
      reaction and are a function of pH because of differential binding of Mg2+ and K+
      to adenine nucleotides, phosphocreatine, and Pi and because of different acidic
      dissociation constants for the metabolites. These results show the need to
      consider the binding of K+ in addition to the previously documented effects of
      Mg2+ in the cytoplasmic milieu. Commercially available software was used to show
      that related problems can be calculated readily on personal computers in
      applications similar to those described here.

PMID- 9176168
TI  - Autosomal dominant polycystic kidney disease decreases anion exchanger activity.
AB  - Liver cysts, the most common extrarenal manifestation of autosomal dominant
      polycystic kidney disease (ADPKD), derive from the intrahepatic biliary
      epithelium (IBE) and are found in 60-75% of ADPKD patients on dialysis. Secretin
      induced secretion by the normal IBE is rich in HCO3-, whereas intact ADPKD liver
      cysts secrete primarily Cl- in response to secretin. To evaluate the mechanisms
      of decreased HCO3- secretion by ADPKD liver cysts, we utilized SV40 large T
      antigen-immortalized normal IBE and ADPKD liver cyst-derived epithelia (LCDE)
      cell lines that we created. These cell lines express biliary but not hepatocyte
      markers. Anion exchanger (AE) function was assessed by the response of
      intracellular pH (pHi) to acute Cl- removal. 2',7'-Bis(carboxyethyl)-5-(6)
      carboxyfluorescein-loaded monolayers were continuously perfused with
      physiological HCO3- buffer containing Cl- or gluconate. In IBE cell line H75 (n =
      6), acute Cl- removal alkalinized pHi at a rate of 0.04 +/- 0.01 min-1. AE
      function was significantly decreased in LCDE cell line CL3 (n = 6) to a rate of
      0.01 +/- 0.01 min-1 after Cl- removal. Northern blot analysis demonstrated
      equivalent levels of AE2 mRNA in both cell lines. AE1 mRNA was undetectable.
      Immunoblot analysis demonstrated the AE2 polypeptide in both cell lines, but the
      level of mature glycosylated AE2 polypeptide was reduced in LCDE cells.
      Immunofluorescence microscopy demonstrated decreased membrane-localized AE2 in
      LCDE cells. These findings suggest that decreased plasmalemmal AE2 may account
      for decreased AE function in LCDE cells and suggest a possible explanation for
      decreased secretion of HCO3- by ADPKD liver cysts.

PMID- 9176169
TI  - Renal assimilation of oligopeptides: physiological mechanisms and metabolic
      importance.
AB  - Assimilation of systemic oligopeptides (di- and tripeptides) is largely a
      function of kidneys. The most specific and unique mechanism utilized for the
      performance of this renal function is transport, followed by intracellular
      hydrolysis and then release of constituent amino acids to the systemic
      circulation. Among tissues examined (liver, kidney, intestine, and muscle),
      kidney is the only tissue capable of accumulating dipeptides in concentrations
      that are greater than their plasma concentrations. Kidney also is the tissue with
      the highest cytoplasmic dipeptidase activity. Intracellular accumulation is
      mediated by two transporters (Pept-1 and Pept-2), both of which have been
      recently cloned. These transporters use dipeptides and tripeptides as substrates
      and rely on protons and membrane potential for their driving force. Pept-1 is a
      low-affinity, high-capacity transporter, and Pept-2 is a high-affinity, low
      capacity transporter. The nutritional and metabolic regulation of renal
      assimilation of oligopeptides is suggested by the selective decrease in dipeptide
      balance across the kidneys of starved human subjects and by the insulin
      stimulation of dipeptide transport by a renal cell line. Peptiduria has been
      observed in a variety of diseases, but the mechanism, except in genetic diseases
      affecting hydrolysis of oligopeptides, is not known. Finally, the capacity for
      active transport of oligopeptides and peptidomimetic drugs enables kidneys to
      play major roles in nutritional and pharmacological therapies.

PMID- 9176170
TI  - Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally
      streptozotocin-diabetic rats.
AB  - The effects of nutrient and neurotransmitter stimuli on insulin release, loss of
      phosphoinositides (PI), and production of inositol phosphates (InsP) were
      investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In
      islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0
      mM D-glyceraldehyde were reduced compared with controls. Contents in
      phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished.
      Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP
      accumulation were both reduced. D-Glucose was unable to increase the levels of
      both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3.
      Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of
      1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and
      InsP generation was still observed. Thus a disturbed coupling between nutrient
      recognition and activation of phospholipase C, possibly together with a shortage
      of available polyphosphoinositides, could be responsible for the altered islet PI
      turnover in the nSTZ rats. It is proposed that such defects may contribute to the
      impairment of glucose-stimulated insulin secretion in this model of non-insulin
      dependent diabetes mellitus.

PMID- 9176172
TI  - Role of the kidney in plasma glucose regulation during hyperglycemia.
AB  - Little is known about the role of the kidney in plasma glucose regulation during
      hyperglycemia. We studied 12 overnight-fasted conscious dogs after either
      intrarenal (IR, n = 6) or peripheral (PH, n = 6) dextrose infusion to maintain
      hyperglycemia without glycosuria. Systemic and renal glucose kinetics were
      measured with [6-3H]glucose, lactate balance was measured by arteriovenous
      difference, and glycogen content was assayed in the kidneys. Plasma glucose
      (approximately 5.5 vs. approximately 6.3 mM), insulin (approximately 70 vs.
      approximately 110 pM), and glucose appearance (approximately 14 vs. approximately
      16 mumol.kg-1.min-1 increased comparably in both groups (P < 0.05). In IR,
      fractional extraction of glucose (FEGlc) increased from 4.1 +/- 0.2 to 16.1 +/-
      0.5% (P < 0.001) and lactate balance reversed to renal output (+1.3 +/- 0.2 vs. 
      0.9 +/- 0.2 mumol.kg-1.min-1, P < 0.01). Glycogen content was twofold higher in
      the left (127 +/- 33 micrograms/g tissue) than in the right kidney (56 +/- 11
      micrograms/g tissue, P < 0.01). In PH, FEGlc decreased from 4.9 +/- 0.6 to 2.2 +/
      0.3% (P < 0.05), renal glucose utilization did not change (approximately 1.3
      mumol.kg-1.min-1); and glycogen content was equal in both kidneys (approximately
      45 micrograms/g tissue). We conclude that, although the kidney plays a minor role
      in plasma glucose disposal in physiological hyperglycemia, increased glucose
      uptake, glycogen storage, and lactate formation precede glycosuria and may
      represent important mechanisms by which the kidney contributes to normalization
      of plasma glucose in diabetes.

PMID- 9176171
TI  - Direct quantification of norepinephrine spillover and hormone output from the
      pancreas of the conscious dog.
AB  - To estimate pancreatic neural activity and to assess the potential role of the
      pancreatic nerves in the regulation of hormone secretion, the methodology
      necessary to quantify neurotransmitter spillover and hormone output in the
      conscious dog was developed. A femoral artery and the superior
      pancreaticoduodenal vein (SPDV) were chronically cannulated, and a flow probe was
      placed on the SPDV. Hormone output was calculated using the pancreatic
      arteriovenous concentration difference and the SPDV plasma flow. Basal glucose
      levels were 103 +/- 1 mg/dl; the pancreatic outputs of insulin, glucagon, and
      pancreatic polypeptide (PP, an index of parasympathetic neural activity) were
      2,900 +/- 700 microU/min, 1,900 +/- 400 pg/min, and 9.3 +/- 4.6 ng/min,
      respectively. Pancreatic norepinephrine (NE) spillover was calculated similarly;
      however, pancreatic extraction of epinephrine was used as an index of NE
      extraction. Basal NE spillover was 3,600 +/- 700 pg/min, greatly exceeding that
      reported using anesthetized, laparotomized dogs. Intravenous glucose infusion
      increased plasma glucose to 146 +/- 13 mg/dl, increased insulin output
      approximately twofold, and suppressed glucagon output by approximately 50%.
      Hyperglycemia markedly reduced PP output. Hyperglycemia failed to influence
      pancreatic NE spillover. Insulin-induced hypoglycemia (36 +/- 2 mg/dl) completely
      suppressed insulin output and stimulated glucagon output (> 10-fold).
      Hypoglycemia increased NE spillover and PP output to 19,900 +/- 4,600 pg/min and
      117 +/- 22 ng/min, respectively. We conclude that pancreatic neurotransmitter
      spillover in the basal state is much higher than previously appreciated and that
      neural signaling to the pancreas is responsive to physiological and
      pathophysiological changes in the metabolic state.

PMID- 9176173
TI  - Adenosine exerts a glycogen-sparing action in contracting rat skeletal muscle.
AB  - The role of adenosine in regulating glycogen breakdown during electrically
      induced muscle contractions was investigated in isolated rat hindquarters
      perfused with a standard medium either lacking or containing 100 microU/ml
      insulin and/or 1.67 nM isoprenaline. Nonselective A1/A2-adenosine receptor
      antagonism via caffeine enhanced (P < 0.05) glycogen breakdown in contracting
      fast-oxidative (FO) fibers by 40%, provided they were exposed to both insulin and
      isoprenaline. Combined A1/A2-receptor antagonism by 8-cyclopentyl-1,3
      dipropylxanthine (CPDPX) plus 3,7-dimethyl-1-proparglyxanthine (DMPX) fully
      reproduced (P < 0.05) this stimulatory effect. Furthermore, CPDPX plus DMPX also
      enhanced (P < 0.05) glycogenolysis during contractions in soleus but not in white
      gastrocnemius muscle. In contrast, CPDPX or DMPX alone did not affect
      glycogenolysis in either fiber type. Muscle adenosine 3',5'-cyclic monophosphate
      concentration during contractions was increased (P < 0.05) by CPDPX plus DMPX in
      both fiber types, whereas glycogen synthase fractional activity was depressed (P
      < 0.05). Phosphorylase activity was not changed by CPDPX plus DMPX. It is
      concluded that adenosine exerts a glycogen-sparing action in oxidative skeletal
      muscle exposed to both insulin and beta-adrenergic stimulation during
      contraction, presumably via stimulation of glycogen synthase activity.

PMID- 9176174
TI  - Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by
      somatostatin.
AB  - Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived
      cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with
      50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that
      MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far
      identified. Treatment of MIN6 cells with somatostatin significantly reduced the
      serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM)
      treatment of MIN6 cells cultured in medium containing 10% serum transiently
      increased c-fos expression levels to 282 +/- 4.7% and then significantly
      decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated
      protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and
      decreased thereafter to 39 +/- 13.3% of the activity before the addition of
      somatostatin (100 nM) into the medium. In addition, the stimulatory effect of
      somatostatin on c-fos expression and MAP kinase activity (early effect) was not
      altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin
      on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX.
      These findings suggest that an inhibition of c-fos expression mediated by cross
      talk between PTX-sensitive G protein signaling and receptor tyrosine kinase
      signaling is one of the mechanisms by which somatostatin inhibits cell growth in
      MIN6 cells.

PMID- 9176175
TI  - Role of the autonomic nervous system in the thermogenic response to food in lean
      individuals.
AB  - The aim of this study was to determine the role of the autonomic nervous system
      (ANS) in obligatory and facultative components of the thermogenic response to
      food (TRF). Nineteen lean, healthy subjects participated in this study, which
      comprised two protocols, each exploring one component of the ANS. In the first
      experimental group, propranolol (prime: 80 micrograms/kg; continuous: 1
      microgram.kg-1.min-1) was infused intravenously to inhibit sympathetic nervous
      activity (SNA), whereas in the second group atropine (prime: 5 micrograms/kg;
      continuous: 5 micrograms.kg-1.min-1) was used to inhibit parasympathetic nervous
      activity (PNA). The TRF was measured on four occasions: 1) after oral ingestion
      of a breakfast, during 0.9% NaCl perfusion, 2) after oral ingestion of the same
      breakfast, during the perfusion of one of the drugs, 3) after intragastric
      injection of a pureed form of the same meal as in part 1, during 0.9% NaCl
      perfusion, and 4) after intragastric feeding, during the administration of one of
      the drugs. Energy expenditure was measured by indirect calorimetry for 30 min
      before and 6 h after ingestion of the meal. Facultative TRF was defined as the
      difference between oral and intragastric TRF. Intragastric feeding significantly
      reduced TRF in both studies: 6.6 +/- 1.0 vs. 8.7 +/- 0.8% of the ingested energy
      in the SNA study and 5.5 +/- 1.6 vs. 7.4 +/- 3.1% in the PNA study. During
      propranolol infusion, TRF was significantly lower than it was during saline
      infusion after oral feeding (6.9 +/- 1.0% vs. 8.7 +/- 0.8% of ingested energy)
      but not after intragastric feeding. During atropine administration, TRF was
      reduced after both oral and intragastric feeding, although statistical
      significance was not reached in the latter. Atropine administration decreased
      gastric emptying (measured with an isotopic method) 2 h postingestion by 50%.
      These results show that the SNA is necessary for the facultative component of TRF
      to occur in humans. The role of the PNA appears to be related to its action on
      gastric emptying.

PMID- 9176176
TI  - Density of fat-free body mass: relationship with race, age, and level of body
      fatness.
AB  - The two-compartment body composition method assumes that fat-free body mass (FFM)
      has a density of 1.100 kg/l. This study tested the hypothesis that FFM density is
      independent of race, age, and body fatness. Subjects were 703 black and white
      subjects, ages 20-94 yr, with body mass index (BMI) 17-35 kg/m2. Body composition
      was assessed using a four-compartment model based on tritium dilution volume,
      body density by underwater weighing, bone mineral by dual-energy X-ray
      absorptiometry, and body weight. No relationship was observed between FFM density
      and race or BMI. A tendency was observed for a lower FFM density only in older
      white women. The difference in percent body fat (delta fat) between the four
      compartment model and underwater weighing was < 2% for all groups. Race, age, and
      BMI explained only 2.3 (women) and 1.4% (men) of the variance in delta fat,
      whereas the total body water fraction of FFM explained 77%. In contrast to
      current thinking, these results show that the assumption of constant FFM density
      is valid in black, elderly, and obese subjects.

PMID- 9176177
TI  - Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of
      anaerobic training.
AB  - The purpose of the present study was to investigate the role of plasma amino
      acids and glutathione (GSH) on the absolute number of leukocyte and lymphocyte
      subpopulations in response to different training programs. Healthy untrained
      subjects were randomly assigned to an 8-wk aerobic (AET) or anaerobic (ANT)
      exercise training program. Absolute number of cell counts did not significantly
      change in AET, whereas a decrease of CD4+ T cell counts (P < 0.05), a fall in
      cells expressing CD45RA+ antigen (P < 0.05), and a marked increase in CD8+ T cell
      numbers (P < 0.01) were noted in ANT at the end of the training period compared
      with baseline values. Furthermore, ANT demonstrated a marked rise (P < 0.001) in
      plasma glutamate from 27.6 +/- 2.8 to 49.8 +/- 5.2 microM and a considerable
      reduction (P < 0.001) of the plasma glutamine pool from 713 +/- 22 to 601 +/- 30
      microM after 8 wk of training. The decrease in glutamine showed a strong positive
      correlation to the individual loss of CD4+ T cells (r = 0.67, P < 0.001). AET
      demonstrated a rise (P < 0.05) in GSH from 20.7 +/- 2.5 to 28.1 +/- 1.5 nmol/mg
      protein at terminal examination. In conclusion, our data indicate impairment of
      the number and activity of CD4+ T cells in response to 8 wk of ANT, which might
      be linked to metabolic factors such as glutamine.

PMID- 9176178
TI  - Determination of protein synthesis in human rectal cancer in situ by continuous
      [1-13C]leucine infusion.
AB  - Previous studies on human colorectal tumor protein synthesis in situ relied on
      techniques that required intra- or perioperative sampling to obtain a sufficient
      biopsy size. The purpose of the present study was to develop a new technique by
      use of new mass spectrometry equipment [capillary gas chromatography (GC)
      combustion isotope ratio mass spectrometry (IRMS)], which allows reduction of the
      necessary sampling size. Thereby, tumor sampling could be done via conventional
      rectosigmoidoscopy, excluding the need for further disturbing invasive measures.
      Fifteen postabsorptive patients with localized rectal cancer received a primed
      constant infusion of [1-13C]leucine (0.16 mumol.kg-1.min-1 constant, 9.6 mumol/kg
      prime). Forceps biopsies were taken after 3 and 6 h. In five subjects, tumor
      tissue and normal mucosa were studied simultaneously. Determination of protein
      bound leucine enrichment was done by GC-IRMS, and GC-quadrupole MS was used to
      determine tracer-to-tracee ratios (tracer/tracee) for free intracellular leucine.
      GC-MS data demonstrated achievement of a steady state in the precursor pool
      enrichment after 3 h of isotope infusion (tracer/tracee at 3 h: 6.34 +/- 0.46%,
      at 6 h: 6.58 +/- 0.38%). Calculation of tumor protein synthesis yielded a
      fractional synthetic rate (FSR) of 1.06 +/- 0.11%/h or 25.5 +/- 2.6%/day (range
      12.0-37.1%/day). At any time, protein-bound leucine enrichment was significantly
      higher in tumor tissue than in normal mucosa of the same subject. However,
      protein synthetic rates were comparable (tumor: 1.09 +/- 0.20%/h, mucosa: 1.29 +/
      0.28%/h). Thus combined GC-combustion IRMS and GC-/quadrupole MS provide a
      simple, reliable, and minimally invasive method to determine tumor FSR in situ,
      thereby excluding interferences common to previous methods. Tumor and mucosa
      tissues are similar with respect to protein synthesis, but they apparently differ
      with respect to leucine extraction from the arterial blood.

PMID- 9176179
TI  - Blockade of the renin-angiotensin-aldosterone system prevents growth hormone
      induced fluid retention in humans.
AB  - To test if the renin-angiotensin-aldosterone system (RAAS) is involved in growth
      hormone (GH)-associated fluid retention, we examined the effect of GH
      administration in the presence or absence of RAAS blockade at different levels on
      body fluid homeostasis. Eight subjects were examined in a controlled, randomized
      double-blinded trial. During four 6-day periods they received subcutaneous GH (6
      IU-m-2) or placebo injections and tablets as follows: 1) placebo and placebo, 2)
      GH and placebo, 3) GH and captopril, and 4) GH and spironolactone. GH increased
      extracellular volume (liters; placebo 18.87 +/- 0.85; GH + placebo 20.43 +/-
      1.01) but this effect was abolished by captopril (GH + captopril 18.82 +/- 0.67)
      and spironolactone (GH + spironolactone 18.99 +/- 0.85). Correspondingly, the GH
      induced reduction in bioimpedance was blocked by captopril and spironolactone.
      Plasma renin and angiotensin II concentrations increased during all three GH
      treatment regimens, whereas plasma aldosterone was increased only after GH plus
      spironolactone. The data demonstrate that GH activates the RAAS and that blockade
      of the RAAS by two separate mechanisms prevents fluid retention normally
      encountered after GH exposure. These observations suggest that the RAAS plays a
      key role in GH-induced regulation of fluid homeostasis.

PMID- 9176180
TI  - Interactions between thyroid hormone and tryptophan transport in rat liver are
      modulated by thyroid status.
AB  - We have identified both N-ethylmaleimide (NEM)-resistant (system T) and NEM
      sensitive (system L1) L-[3H]tryptophan transporters in sinusoidal membrane
      vesicles (SMVs) from euthyroid, hypothyroid (propylthiouracil-treated), and
      hyperthyroid [L-3,5,3'-triiodothyronine (L-T3)-injected] rats. L-[125I]T3
      associates with SMVs largely by surface binding. Kinetic characteristics of
      tryptophan uptake and T3 binding (transporter or receptor abundance and substrate
      affinity) are not significantly affected by thyroid status. T3 and thyroxine (T4)
      inhibit NEM-resistant tryptophan uptake in SMVs to an extent dependent on the
      thyroid status of the donor rat, increasing in the order hypothyroid < euthyroid
      < hyperthyroid; the inhibitor constant for this inhibition (0.3 microM T3) is
      equal to the dissociation constant for T3 binding. Both T3 binding and T3
      inhibition of tryptophan transport in SMVs are markedly reduced by treatments
      (Triton X-100 or trypsin) that do not significantly affect vesicle integrity or
      transport of tryptophan and glucose. T3 and/or T4 transport at the liver-plasma
      interface may be facilitated by direct interactions between hormone receptors and
      system T transporter proteins. Modulation of such interactions may be important
      for control of hepatic T4 and/or T3 turnover and aromatic amino acid metabolism
      during altered thyroid status.

PMID- 9176181
TI  - Fetal sheep endocrine responses to sustained hypoxemic stress after chronic fetal
      placental embolization.
AB  - The purpose of this study was to determine the endocrine and circulatory
      responses of the ovine fetus, near term, to sustained hypoxemic stress
      superimposed on chronic hypoxemia. Fetal sheep were chronically embolized (n = 7)
      for 10 days between 0.84 and 0.91 of gestation via the descending aorta until
      arterial oxygen content was decreased by approximately 30%. Control animals (n =
      8) received saline only. On experimental day 10, both groups were embolized over
      a 6-h period until fetal arterial pH decreased to approximately 7.00. Regional
      distribution of lower body blood flows was measured on day 10, before and at the
      end of acute embolization. On day 10, the chronically embolized group had lower
      arterial oxygen content (P < 0.05), Po2 (P < 0.01), and placental blood flow (P <
      0.05) than controls and higher prostaglandin E2 (PGE2) and norepinephrine plasma
      concentrations (both P < 0.05). In response to a superimposed sustained hypoxemic
      stress, there was a twofold greater increase in PGE2 in the chronically embolized
      group than in the control group (P < 0.05). However, the increase in fetal plasma
      cortisol in response to superimposed hypoxemic stress was similar in both groups,
      despite significantly lower adrenocorticotropic hormone and adrenal cortex blood
      flow responses in the chronically hypoxemic group (both P < 0.05). We conclude
      that PGE2 response to a sustained superimposed reduction in placental blood flow,
      leading to metabolic acidosis, is enhanced under conditions of chronic hypoxemia
      and may play an important role for the maintenance of the fetal cortisol response
      to an episode of superimposed acute stress.

PMID- 9176182
TI  - Comparative metabolism and distribution of rabbit heparin cofactor II and rabbit
      antithrombin in rabbits.
AB  - The metabolic characteristics of two rabbit plasma thrombin inhibitors, heparin
      cofactor II (HCII) and antithrombin (AT), have been compared in healthy young
      rabbits. Purified HCII and AT-alpha were differentially radiolabeled (125I, 131I)
      and injected intravenously; blood samples were taken at prescribed intervals over
      7 days. From the plasma clearance curves of protein-bound radioactivities,
      fractional catabolic rates and compartmental distributions were calculated using
      a three-compartment model. The whole body fractional catabolic rate for HCII (jt,
      0.43/day, equivalent to t1/2 = 1.61 days) was significantly faster than for AT
      (jt, 0.37/day; t1/2 = 1.89 days; P < 0.005). The fractional distribution of HCII
      in the intravascular compartment (Ap, 0.20) and in the extravascular compartment
      (Ac, 0.63) differed significantly from AT (Ap, 0.30; Ac, 0.56). From the
      catabolic data and blood concentrations, absolute quantities of HCII and AT
      catabolized by a 3-kg rabbit amounted to 12.8 and 19.9 mg/day, respectively,
      equivalent to a molar ratio, AT/HCII, of 1.7. The catabolic molar ratio was
      compared with the relative release rates of HCII and AT from perfused rabbit
      livers. Both proteins were released from the liver, the molar ratio in the
      perfusate rising to approximately 1.4 at 2.5 h. This report increases our
      understanding of the in vivo dynamics of these two proteins.

PMID- 9176183
TI  - Prostaglandin-endoperoxide H synthase-2 expression and activity increases with
      term labor in human chorion.
AB  - We investigated the changes in prostaglandin-endoperoxide H synthase (PGHS)
      specific activity and the levels and distribution of PGHS-1 and PGHS-2 mRNA in
      chorion collected at term before the onset of labor (CS) and after term labor and
      delivery (SL). PGHS specific activity and PGHS-2 mRNA abundance were higher in
      chorion collected after SL compared with that obtained at CS (P < 0.001); there
      was no difference in the levels of PGHS-1 mRNA between CS and SI, tissues. The
      increase in PGHS specific activity at SL was significantly correlated with PGHS-2
      mRNA expression (P < 0.05) but not with PGHS-1 mRNA levels. In situ hybridization
      indicated that the pervasiveness of staining for PGHS-1 mRNA throughout full
      thickness membranes did not change with labor onset; however, a greater number of
      cells expressed PGHS-2 in SL tissues. Our results demonstrate a selective
      increase in PGHS-2 expression and activity in chorion trophoblasts and
      mesenchymal cells with term labor onset. These observations are similar to those
      concerning amnion and imply that a concerted mechanism may exist in the fetal
      membranes to induce PGHS-2 expression at labor.

PMID- 9176184
TI  - Postprandial stimulation of muscle protein synthesis is independent of changes in
      insulin.
AB  - Protein synthesis in skeletal muscle is markedly stimulated (approximately 180%
      of control rate) within 3 h of oral feeding in mice subjected to an overnight
      fast (18 h). The stimulation of protein synthesis is the result of a faster rate
      of translation initiation; however, neither the mediators (i.e., hormones or
      nutrients) nor the mechanisms responsible for the effect of feeding are well
      understood. Results of the present study revealed that the amount of eukaryotic
      initiation factor 4E (eIF-4E) present in the phosphorylated form (i.e., 70%) was
      not changed after overnight starvation or a subsequent 3-h refeeding period
      compared with muscles from freely fed mice. In contrast, the phosphorylation
      state of the eIF-4E binding protein 1 (4E-BP1) was changed with nutritional
      state. Starvation increased the proportion of the unphosphorylated form of 4E
      BP1, whereas feeding promoted a shift to the more highly phosphorylated forms of
      the protein. Moreover, starvation increased the amount of 4E-BP1 recovered by
      almost threefold, indicative of an increase in the eIF-4E.4E-BP1 complex. The
      increased association of 4E-BP1 with eIF-4E was completely reversed within 3 h of
      feeding. Starvation and refeeding also altered the amount of eIF-4G that
      coimmunoprecipitated with eIF-4E. However, in contrast to the results obtained
      for 4E-BP1, starvation decreased the amount of eIF-4G recovered in the eIF-4E
      immunoprecipitate, suggesting that starvation causes a decrease in the formation
      of the active eIF-4F complex. The alterations in 4E-BP1 phosphorylation and
      association of 4E-BP1 and eIF-4G with eIF-4E observed in control mice in response
      to starvation and refeeding were also observed in diabetic mice exhibiting
      characteristics of type I or type II diabetes subjected to the same conditions,
      suggesting that insulin alone does not mediate the observed changes. Thus the
      integrated feeding response represents an important area of investigation for
      understanding the regulation of translation initiation.

PMID- 9176185
TI  - Effects of exercise and feeding on the hexosamine biosynthetic pathway in rat
      skeletal muscle.
AB  - Products of the hexosamine biosynthesis pathway (HSNP) have been implicated in
      glucose-induced insulin resistance. We measured the major products of HSNP, UDP-N
      acetyl hexosamines (UDP-HexNAc), and the activity of L-glutamine: D-fructose-6
      phosphate amidotransferase (GFAT, rate-limiting enzyme) in rat hindlimb muscles
      immediately after exercise and 1, 3, and 16 h postexercise (swimming) in fed and
      fasted rats and sedentary controls. Muscle glycogen decreased by 50-75%
      postexercise. In sedentary rats, muscle GFAT activity decreased by approximately
      30% (P < 0.002) after an 18-h fast. GFAT activity was not affected by exercise
      under any condition. Muscle UDP-HexNAc increased approximately 30% postexercise
      (P < 0.01) in ad libitum-fed but not in fasted rats. UDP-HexNAc remained elevated
      (approximately 30%, P < 0.002) for 16 h if animals were fed postexercise.
      Concentrations of UDP-hexoses, GDP-mannose, and UDP were unchanged postexercise.
      Conclusions are that muscle GFAT activity is regulated by the nutritional state
      but not by acute exercise. Glucose flux via HNSP may be increased postexercise in
      muscles of ad libitum-fed rats. Increased HSNP products may serve as negative
      feedback regulators to limit excessive muscle glycogen deposition postexercise.

PMID- 9176186
TI  - Effects of diabetes on rodent cardiac thyroid hormone receptor and isomyosin
      expression.
AB  - Previous studies show that diabetes induces marked transformations in cardiac
      myosin heavy chain (MHC) gene expression that are somehow linked to the cellular
      action of thyroid hormone 3,5,3'-triiodothyronine (T3). In this study, we tested
      the hypothesis that diabetes induces a reduced expression of thyroid hormone
      receptors (TRs), which are known to be important transcription factors
      interacting with thyroid response elements (TREs) in the promoter region of both
      alpha- and beta-MHC genes. Adult female rats were randomly assigned to either a
      normal control (NC) or diabetic (D) group. Three and/or six weeks after induction
      of diabetes via streptozotocin injection, the hearts of the animals were analyzed
      for MHC and TR mRNA isoforms expression, nuclear T3 binding, and nuclear extract
      interaction with a palindromic TRE. Results showed that diabetes induced
      significant alteration in alpha- and beta-MHC expression. Northern blot analyses
      indicated no diabetes-associated differences in TR isoform mRNA signals. Cardiac
      nuclear T3 binding studies suggested no differences in either the binding
      capacity or the equilibrium binding constant among the two groups, indicating no
      changes in either the number of nuclear TRs or their affinity for T3.
      Furthermore, gel mobility shift assays detected no difference between NC and D
      groups for cardiac nuclear extract binding to palindromic TRE. Collectively,
      these findings suggest that, whereas diabetes exerts a profound effect on cardiac
      isomyosin gene expression, the underlying mechanism, although dependent on
      factors linked to T3 function, does not involve alterations in TR expression.

PMID- 9176187
TI  - Exercise training reverses insulin resistance in muscle by enhanced recruitment
      of GLUT-4 to the cell surface.
AB  - The effects of exercise training on cell surface GLUT-4 in skeletal muscle of the
      obese (fa/fa) Zucker rat were investigated using the impermeant glucose
      transporter photoaffinity reagent 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1,3
      bis- (D-mannos-4-yloxy)-2-propylamine (ATB-BMPA). In the absence of insulin, 3-O
      methyl-D-glucose transport activity was no different in either fast-twitch
      (epitrochlearis) or slow-twitch (soleus) muscles of trained and sedentary obese
      rats. Likewise, basal ATB-BMPA-labeled GLUT-4 was not altered in these muscles
      with training. In contrast, the trained group exhibited significantly greater
      insulin-stimulated (2 mU/ml) glucose transport activity in epitrochlearis muscles
      than the sedentary group (0.53 +/- 0.03 vs. 0.18 +/- 0.03 mumol.g-1 x 10 min-1
      for trained and sedentary, respectively), which was paralleled by a significant
      enhancement of insulin-stimulated cell surface GLUT-4 (5.33 +/- 0.20 vs. 1.57 +/-
      0.14 disintegrations.min-1.mg-1 for trained and sedentary, respectively).
      Exercise training, however, did not alter insulin-stimulated glucose transport
      activity or cell surface GLUT-4 in soleus muscles. Finally, exercise training did
      not alter the ability of muscle contraction to elevate glucose transport activity
      or cell surface GLUT-4 in either epitrochlearis or soleus muscles of the obese
      rat. These results indicate that training improves insulin-stimulated glucose
      transport in muscle of the obese Zucker rat by increasing GLUT-4 content and by
      altering the normal intracellular distribution of these transporters such that
      they are now capable of migrating to the cell surface in response to the insulin
      stimulus.

PMID- 9176188
TI  - Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi
      receptor interaction.
AB  - Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial
      membranes with iodinated oxytocin antagonist (OTA), followed by detergent
      solubilization and size selection, showed that radioactivity eluted in two
      distinct peaks: one corresponding in size to the isolated receptor (approximately
      60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa
      fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT)
      increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold
      in a dose-dependent manner. The effects of OT were blocked by coincubation with
      OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak
      were identified by immunoadsorption. Significant amounts of both G alpha q/11 and
      G alpha i3 were associated with the OTR; a lesser amount of G alpha s was
      complexed. Using the same approach but with antibodies to effector enzymes, we
      observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated
      with the OTR. The results corroborate the well-established interaction of OTR
      with Gq and further show that Gi coupling might be an important component of OTR
      signal transduction. To further investigate the interaction of Gi with the OTR,
      we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact
      myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated
      ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT
      treatment. These findings with pertussis toxin strongly indicate that OTR is
      coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled
      receptor) was demonstrable in the myometrium only before the end of gestation and
      after parturition and accounted for about one-half the 125I-OTA binding activity.
      At term, there was about a fivefold increase in binding and almost a complete
      shift to the 240- to 320-kDa-size complex. Thus the established increased
      sensitivity of the myometrium to OT at term could be the result of both
      upregulation of OTRs and an increase in the fraction of receptors coupled to
      signal transduction components, one of which is Gi.

PMID- 9176189
TI  - Intrauterine growth restriction does not alter response of protein synthesis to
      feeding in newborn pigs.
AB  - This study aimed to determine the effect of intrauterine growth restriction
      (IUGR) on the acute response of tissue protein synthesis to feeding in newborn
      pigs. Newborn pigs of sows fed either control or protein-restricted diets
      throughout gestation were designated C or IUGR, respectively. Both groups were
      either fasted for 9 h after birth or fed hourly 30 ml colostrum/kg body wt for
      2.75 h after a 6-h fast. Fractional rates of tissue protein synthesis (Ks) were
      measured in vivo with a flooding dose of L-[4-3H]phenylalanine. Birth weight was
      reduced by 33% in IUGR pigs. IUGR had no effect on Ks in skeletal muscles, heart,
      liver, jejunum, or pancreas. Feeding stimulated tissue Ks similarly in C and IUGR
      pigs. Fasting plasma insulin concentrations and their rise with feeding were
      unaffected by IUGR. Plasma insulin-like growth factor I (IGF-I) concentrations
      were reduced by 42% in IUGR pigs and were not altered by feeding in either IUGR
      or C pigs. There were positive nonlinear relationships between tissue Ks and
      circulating concentrations of insulin. The results indicate that, in newborn
      pigs, tissue Ks are unaffected by IUGR, despite reduced plasma IGF-I
      concentrations. The efficiency with which nutrients stimulate tissue Ks is also
      not altered by IUGR, perhaps because the rise in plasma insulin concentrations
      with feeding is unaffected by IUGR.

PMID- 9176191
TI  - Placental transport of threonine and its utilization in the normal and growth
      restricted fetus.
AB  - Placental transport and fetoplacental utilization of threonine (Thr) were
      compared at 130 +/- 1 days gestational age between seven control ewes (C) and six
      ewes in which intrauterine growth restriction (IUGR) had been induced by exposure
      to high ambient temperature from 33 +/- 1 to 112 +/- 2 days of gestation. The
      fluxes were measured using simultaneous intravenous infusions of L-[1-13C]Thr
      into the mother and L-[U-14C]Thr into the fetus. The IUGR group had less fetal
      weight (1.27 +/- 0.14 vs. 3.10 +/- 0.10 kg, P < 0.01) and placental weight (120
      +/- 17 vs. 295 +/- 14 g, P < 0.01) than the C group. The direct flux of maternal
      Thr into the fetal systemic circulation was less in the IUGR fetuses, both
      relative to fetal weight (1.40 +/- 0.19 vs. 2.19 +/- 0.18 mumol.min-1.kg fetus-1,
      P = 0.0107) and placental weight (1.5 +/- 0.2 vs. 2.3 +/- 0.2 mumol.min-1.100 g
      placenta-1, P = 0.0187). In both groups, there was excretion of CO2 produced from
      fetal Thr. The rate of CO2 production from fetal plasma Thr carbon by fetus plus
      placenta was reduced in the IUGR group (1.50 +/- 0.23 vs. 2.86 +/- 0.32 mumol.min
      1.kg fetus-1, P = 0.0065). We conclude that the flux of maternal Thr into the
      IUGR fetus is markedly reduced because of a reduction in placental mass and
      because of a weight-specific reduction in Thr placental transport. The reduced
      flux is routed into fetal Thr accretion via a decrease in fetal Thr oxidation.

PMID- 9176190
TI  - Progesterone-induced changes in sleep in male subjects.
AB  - Progesterone administration induces a reduction of the vigilance state in humans
      during wakefulness. It has been been suggested that this effect is mediated via
      neuroactive metabolites that interact with the gamma-aminobutyric, acidA (GABAA)
      receptor complex. To investigate the effects of progesterone administration on
      the sleep electroencephalogram (EEG) in humans we made polysomnographic
      recordings, including sleep stage-specific spectral analysis, and concomitantly
      measured plasma concentrations of progesterone and its GABA-active metabolites 3
      alpha-hydroxy-5 alpha-dihydroprogesterone (allopregnanolone) and 3 alpha-hydroxy
      5 beta-dihydroprogesterone (pregnanolone) in nine healthy male subjects in a
      double-blind placebo-controlled crossover study. Progesterone administration at
      9:30 PM induced a significant increase in the amount of non-rapid eye movement
      (REM) sleep. The EEG spectral power during non-REM sleep showed a significant
      decrease in the slow wave frequency range (0.4-4.3 Hz), whereas the spectral
      power in the higher frequency range (> 15 Hz) tended to be elevated. Some of the
      observed changes in sleep architecture and sleep-EEG power spectra are similar to
      those induced by agonistic modulators of the GABAA receptor complex and appear to
      be mediated in part via the conversion of progesterone into its GABA-active
      metabolites.

PMID- 9176192
TI  - Energy expenditure of adult male rhesus monkeys during the first 30 mo of dietary
      restriction.
AB  - Energy expenditure, activity, and body composition were measured in 30 adult male
      rhesus monkeys used in a study having the long-term goal of determining the
      effects of moderate dietary restriction (DR) on aging. All animals were fed a
      defined diet, with the restricted animals maintained at approximately 70% of the
      caloric intakes of the controls. After 12 mo of DR, body fat mass of restricted
      monkeys was 33% less than that of controls (P = 0.004), whereas lean body mass
      differences were not present until after 24 mo. At the 24- and 30-mo assessments,
      nighttime energy expenditure was significantly reduced (P < 0.01) in the
      restricted compared with control monkeys after adjustment for lean body mass
      differences, whereas morning, afternoon, and total energy expenditure were not
      significantly different (P > 0.05). No significant differences (P > 0.05) in
      activity were noticed between treatment groups at any time point. DR resulted in
      a prolonged decrease in resting energy expenditure, which could contribute to the
      possible life-extending action of this treatment.

PMID- 9176193
TI  - Altered energy balance and cytokine gene expression in a murine model of chronic
      infection with Toxoplasma gondii.
AB  - The temporal pattern of changes in energy balance and cytokine mRNA expression in
      spleen and brain were examined in a mouse model of infection with Toxoplasma
      gondii. During days 1-7 postinfection, food intake was unaltered, but energy
      expenditure was significantly increased, and this was associated with elevated
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon
      (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose
      onset coincided with elevated IL-2, and at the end of the acute phase of
      cachexia, the dual anorexic and hypermetabolic states were associated with the
      cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN
      gamma. In the chronic phase of the infection, the mice showed either partial
      weight recovery (gainers) or no weight regain (nongainers). The infected gainers,
      though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA
      was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected
      nongainers continued to show both anoroxia and hypermetabolism, which were
      associated with elevations in all cytokines examined and particularly those of
      the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a
      distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs.
      anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial
      weight recovery.

PMID- 9176194
TI  - Effect of GH/IGF-I deficiency on long-term renal changes and urinary albumin
      excretion in diabetic dwarf rats.
AB  - Growth hormone (GH) and insulin-like growth factor I (IGF-I) may play a role in
      early diabetic renal and glomerular growth and in the later development of
      experimental diabetic kidney disease. Rats from a genetic GH/IGF-I-deficient
      dwarf rat strain were made streptozotocin diabetic and were compared with
      nondiabetic dwarf rats. GH/IGF-I-intact rats with and without diabetes served as
      controls. After 6 mo of diabetes, kidney weight and total glomerular volume
      increased significantly in GH/IGF-I-intact diabetic rats compared with the
      nondiabetic GH/IGF-I-intact rats (P < 0.05), whereas the diabetic dwarf rats had
      insignificant changes compared with dwarf control rats. By the end of the study,
      urinary albumin excretion (UAE) increased from similar base levels of
      approximately 15-20 micrograms/24 h to 473 +/- 52 (SE) micrograms/24 h in GH/IGF
      I-intact diabetic rats compared with 151 +/- 32 micrograms/24 h in diabetic dwarf
      rats (P < 0.01). In conclusion, isolated GH/IGF-I deficiency reduces the degree
      of renal and glomerular hypertrophy and the increase in UAE after 6 mo of
      experimental diabetes in GH/IGF-I-deficient rats.

PMID- 9176195
TI  - Assessment of insulin sensitivity with minimal model: role of model assumptions.
AB  - Insulin sensitivity is frequently assessed with the minimal model (MM) and the
      insulin-modified intravenous glucose tolerance test (MIVGTT). To ascertain the
      validity of this approach, the mechanisms by which the MM estimates glucose
      effectiveness and insulin sensitivity (SG and SI, respectively) from the data are
      analyzed theoretically. Published data and new labeled MIVGTTs in normal and non
      insulin-dependent diabetic (NIDDM) subjects are used as reference data. One
      reason for the reported difficulty in estimating SI in NIDDM is the inadequacy of
      the MM to describe the data. SG is a biased estimate of the fractional glucose
      clearance (FGC) at basal insulin, and SI is a biased estimate of the average
      slope of the insulin concentration-FGC curve. The monocompartmental assumption
      and the role of glucose production in the MM are causes of bias. The bias is
      fairly constant across the spectrum of glucose tolerance (SG: approximately 150%
      overestimate; SI: approximately 30% underestimate). Also, SI is not expected to
      account satisfactorily for hepatic insulin sensitivity. Finally, by the use of SG
      and SI, FGC at a target insulin level (FGCMM) can be estimated. FGCMM agrees well
      with the analogous clamp index (difference 10%; correlation: r = 0.88, P < 0.002)
      and, in NIDDM, has a lower coefficient of variation than SI (57 vs. 82%). In
      conclusion, this analysis indicates that the MM is a sufficiently reliable method
      for the assessment of insulin sensitivity if it is used cautiously.

PMID- 9176196
TI  - Oxidant stress reduces insulin responsiveness in 3T3-L1 adipocytes.
AB  - Increased oxidant stress has been suggested to occur in diabetes and to
      contribute to the development of late diabetic complications. Whether oxidant
      stress plays a role in the development or progression of insulin resistance is
      not known. In this study we hypothesized that exposing 3T3-L1 adipocytes to
      prolonged micromolar concentrations of H2O2 would reduce their acute metabolic
      responses to insulin stimulation. 3T3-L1 adipocytes exposed to 25 mU/ml glucose
      oxidase (GO) for 18 h exhibited a threefold increase in basal 2-deoxyglucose (2
      DG) uptake activity. However, net increase in 2-DG uptake activity after acute
      insulin (100 nM) stimulation was 355 +/- 56 pmol.mg protein-1.min-1 in control
      vs. 198 +/- 41 pmol.mg protein-1.min-1 in GO-pretreated cells (P < 0.05). Basal
      lipogenesis activity was significantly enhanced by GO, but acute insulin
      stimulation resulted in significantly reduced lipogenesis activity (29 +/- 4 vs.
      11 +/- 1 nmol glucose/well for control and 50 mU/ml GO, respectively, P = 0.001).
      Glycogen synthase alpha activity was reduced by GO (78 +/- 1 vs. 43 +/- 2 pmol
      UDP-glucose.mg protein-1.min-1, P = 0.03), whereas insulin stimulation of
      glycogen synthase was reduced, exhibiting a right shift in the insulin dose
      response curve. These effects of GO were associated with increased GLUT-1 and
      reduced GLUT-4 protein and mRNA content. In conclusion, our data suggest that
      oxidant stress alters glucose transporters expression and insulin-stimulated
      metabolism in 3T3-L1 adipocytes.

PMID- 9176197
TI  - Clenbuterol increases the expression of myogenin but not myoD in immobilized rat
      muscles.
AB  - Immobilization of one hindlimb of young rats in plantar flexion for 3 days led to
      changes in the plantaris muscles. These comprised a loss of muscle mass and a
      reduction in protein and RNA content, but no change in the transcript levels of
      the myogenic regulatory factors myogenin and myoD. Dietary administration of the
      beta-adrenoceptor agonist clenbuterol (2 mg/kg diet), which has been shown to
      ameliorate muscle wasting in a wide range of atrophic conditions, also limited
      muscle wasting in terms of weight, protein, and RNA in the immobilized plantaris
      muscles. In addition, drug treatment in immobilized plantaris muscles was
      associated with a marked increase in the steady-state levels of mRNA for myogenin
      (approximately 360% increase over control) but not myoD. These data provide the
      first evidence for independent changes in these two myogenic regulatory factors
      in immobilized muscle and suggest that the action of clenbuterol on these factors
      may depend on the mechanistic basis for the atrophic response.

PMID- 9176198
TI  - Hyperpermeability of intestinal epithelial monolayers is induced by NO: effect of
      low extracellular pH.
AB  - Nitric oxide (NO.) increases the permeability of Caco-2BBe enterocytic
      monolayers. Many of the toxic effects of NO. are thought to be mediated by the
      peroxynitrite anion (ONOO-), which, under mildly acidic conditions, can rearrange
      to yield an intermediate with reactivity similar to toxic OH.. Accordingly, we
      assessed the permeability of Caco-2BBe cells grown on permeable supports for 24 h
      in media titrated to normal or acidic extracellular pH (pHo) with or without the
      NO. donors 3-morpholinosydnonimine (SIN-1) or sodium nitroprusside (SNP).
      Incubation with 2 mM SIN-1 at pHo 6.8 or 0.6 mM SNP at pHo 6.5 increased
      permeability (apical-to-basolateral flux of fluorescein sulfonic acid), whereas
      at pHo 7.4 permeability was unaffected by these concentrations of NO. donors.
      Accumulation of NO2/NO3 in medium (index of NO. release) was not increased by
      incubation of cells with SIN-1 or SNP under mildly acidic conditions. Under
      acidic but not control conditions, incubation with SIN-1 caused disruption of
      perijunctional actin filaments as assessed by fluorescence microscopy. At pHo 6.8
      and 6.5 (but not 7.4), SIN-1 significantly decreased intracellular levels of both
      ATP and glutathione. Incubation with 5 mM deferoxamine or 500 uM ascorbic acid
      (ONOO- scavengers) abrogated SIN-1-induced hyperpermeability. We conclude that
      mild acidosis augments NO.-induced intestinal epithelial permeability, possibly
      by promoting oxidant-mediated cytoskeletal damage and/or ATP depletion.

PMID- 9176200
TI  - L-glutamine stimulates intestinal cell proliferation and activates mitogen
      activated protein kinases.
AB  - We studied the mechanisms by which L-glutamine (Gln), a major fuel for
      enterocytes, signals proliferation in intestinal epithelial cell lines. Gln was
      additive to epidermal growth factor (EGF) and insulin-like growth factor I (IGF
      I) in stimulating DNA synthesis, as assessed by [3H]thymidine incorporation.
      Extracellular signal-regulated kinases (ERKs) p42mapk and p44mapk and Jun nuclear
      kinases (JNKs) phosphorylate and activate nuclear transcription factors. Proteins
      of the c-Jun, ATF-2, and c-Fos families aggregate to form DNA-binding homodimers
      or heterodimers called activating protein 1 (AP-1). In vitro assays and
      functional assays of phosphorylation demonstrated that Gln activates both ERKs
      and JNKs, resulting in a fourfold increase in AP-1-dependent gene transcription.
      Gln was required for EGF signaling through ERKs. Maximal stimulation of
      proliferation required approximately 2.5 mM Gln. c-Jun mRNA levels responded to
      Gln in "Gln-starved" porcine IPEC-J2 cells and in rat IEC-6 cells. Although Gln
      metabolism is required for the proliferative response, several Gln by-products
      did not stimulate [3H]thymidine incorporation, with the exception of arginine.
      Gln may be a unique nutrient for enterocytes, capable of dual signaling and
      augmenting the effects of growth factors that govern cellular proliferation and
      repair.

PMID- 9176199
TI  - Apolipoprotein secretion and lipid synthesis: regulation by fatty acids in
      newborn swine intestinal epithelial cells.
AB  - The IPEC-1 newborn swine intestinal epithelial cell line was used to determine
      the effects of the uptake of various fatty acids on the secretion of
      apolipoprotein (apo) B and apo A-I, as well as triglyceride and phospholipid.
      Long-chain saturated fatty acids were taken up and stimulated triglyceride
      synthesis, and palmitic (16:0) and stearic (18:0) acids also stimulated
      phospholipid synthesis. However, these fatty acids did not enhance triglyceride,
      phospholipid, or apo B or apo A-I secretion. Oleic acid (18:1) was the most
      effective of all fatty acids tested in stimulating triglyceride synthesis and the
      secretion of triglyceride, phospholipid, and apo B. Linoleic (18:2) and linolenic
      (18:3) acids were no more effective than long-chain saturated fatty acids in
      stimulating these processes. With saturated fatty acids, apo A-I followed the
      same secretory pattern as apo B. However, among the unsaturated fatty acids,
      oleic acid was the least effective and linolenic acid was the most effective in
      stimulating apo A-I secretion. Basolateral secretion of lipid and apolipoproteins
      by differentiated IPEC-1 cells is differentially regulated by apical exposure to
      fatty acids.

PMID- 9176201
TI  - Modulation of hormone-induced calcium oscillations by intracellular pH in rat
      hepatocytes.
AB  - Single isolated rat hepatocytes were used to investigate the influence of
      intracellular pH (pHi) on hormone-induced cytosolic Ca2+ oscillations, using
      videofluorescence microscopy. Although pHi did not vary after alpha-adrenergic
      stimulation, manipulations of pHi induced pronounced alterations in the frequency
      of oscillations. Increasing the resting pHi with ammonium chloride (5-20 mM),
      trimethylammonium (2-10 mM), or triethylammonium (1.2-8 mM) reduced the frequency
      of oscillations. A change in pHi of > 0.25 was sufficient to reversibly inhibit
      oscillations. This effect could be overcome by increasing the agonist
      concentration or by adding 8-bromoadenosine 3',5'-cyclic monophosphate, an agent
      known to potentiate the alpha-adrenergic response. Cellular acidification,
      obtained by the ammonium prepulse method as well as by application of acetate or
      the ionophore nigericin, in the continuous presence of agonist was accompanied by
      a modest frequency increase of the oscillations, leading in some cases to an
      overstimulated state. This study indicates that pHi, within a range of values
      expected to occur in vivo (0.1-0.2 pH units), exerts a chronotropic effect on
      phenylephrine-induced Ca2+ oscillations. In contrast, oscillations induced by ADP
      or vasopressin were pHi invariant.

PMID- 9176202
TI  - Spontaneous activity of guinea pig ileum longitudinal muscle regulated by Ca(2+)
      activated K+ channel.
AB  - Isolated guinea pig ileum displayed spontaneous contraction and fluctuation of
      membrane potential originating from the longitudinal muscle. Transmural
      stimulation of the enteric nerve plexus evoked contractions that were followed by
      lowered muscle tone and decreased spontaneous activity. The Na+ channel blocker
      tetrodotoxin, N-type Ca2+ channel blockers omega-conotoxins GVIA and MVIIA, the
      muscarinic receptor antagonist atropine, and inhibitory mediators alpha, beta
      methylene-ATP and sodium nitroprusside all inhibited stimulation-evoked
      contraction while restoring spontaneous motility. L-type Ca2+ channel blockers
      nifedipine and calciseptine completely suppressed evoked and spontaneous
      contractions. Blockade of the large-conductance Ca(2+)-activated K+ (Kca) channel
      with charybdotoxin (but not of small-conductance Kca channel by apamin or of ATP
      regulated K+ channel by glybenclamide) induced spikelike depolarization,
      inhibited nerve stimulation-evoked membrane hyperpolarization, and increased
      spontaneous activity. The results suggest that the large-conductance Kca channel
      is constitutively activated for modulations of spontaneous activity, and that
      muscle excitation, through elevation of Ca2+ levels, stimulates the large
      conductance Kca channel to suppress spontaneous activity.

PMID- 9176204
TI  - Hepatobiliary transport mechanism for the cyclopentapeptide endothelin antagonist
      BQ-123.
AB  - The hepatobiliary transport of an anionic cyclopentapeptide endothelin
      antagonist, BQ-123, was studied in rats. Biliary excretion of [3H]BQ-123 was
      extensive in vivo (approximately 75% of intravenous infusion rates). Liver-to
      plasma and bile-to-liver concentration ratios at steady state were approximately
      3 and 200, respectively, suggesting that hepatic uptake and biliary excretion are
      concentrative processes. The biliary excretion clearance exhibited a saturation
      at a hepatic concentration of > 100 nmol/g liver and was markedly reduced in
      Eisai hyperbilirubinemic rats, which have a hereditary defect of canalicular
      multispecific organic anion transporter. An ATP-dependent and saturable uptake of
      BQ-123 by isolated canalicular membrane vesicles was observed in vitro. Impaired
      transport of BQ-123 was also confirmed in canalicular membrane vesicles prepared
      from Eisai hyperbilirubinemic rats. These results demonstrate that the biliary
      excretion process is ATP-driven primary active transport. It is proposed that a
      canalicular multispecific organic anion transporter is mainly responsible for the
      biliary excretion of BQ-123.

PMID- 9176203
TI  - Upregulation of rat intestinal uroguanylin mRNA by dietary zinc restriction.
AB  - A cDNA for the rat uroguanylin precursor was identified, by differential display
      of intestinal mRNA, as upregulated in zinc-deficient rats and subsequently was
      cloned. The cDNA and deduced amino acid sequences show a high degree of homology
      to human and opossum preprouroguanylin sequences. When used as a probe for
      Northern blot analysis of RNA from rat intestinal mucosa, the uroguanylin cDNA
      hybridized to a single species of mRNA that was 2.5-fold more abundant in zinc
      deficiency. A tissue distribution survey indicates that although the small
      intestine expresses a disproportionately high level of preprouroguanylin, this
      hormone precursor is also expressed in the colon, stomach, kidney, thymus, and
      testis. The induction by zinc deficiency is the first reported case of gene
      regulation for this hormone. These results also suggest a potential mechanism to
      explain, at least in part, the beneficial effects of zinc supplementation for
      secretory diarrhea prevalent in many areas of the world.

PMID- 9176206
TI  - Demonstration and characterization of motilin-binding sites in the rabbit
      cerebellum.
AB  - This is the first report on central motilin receptors. Autoradiography on
      cerebellar slices revealed specific motilin-binding sites in the molecular layer
      of the cortex. Scatchard analysis of cold saturation studies showed the existence
      of a high-(pKd,hi = 9.07 +/- 0.09, where pKd is the negative logarithm of the
      dissociation constant) and a low-affinity binding site (pKd,lo = 6.56 +/- 0.09).
      Similar affinities were found with rabbit motilin and with the porcine (po)
      antagonist [Phe3, Leu13]po-motilin. Feline and canine motilin had a markedly
      lower affinity for the low-affinity site (pKd,lo = 5.29 and 4.58, respectively);
      chicken motilin had a lower affinity for both sites (pKd,hi = 8.36, pKd,lo =
      3.97). Erythromycin A and its derivative N-trimethyl erythromycin A cnol ether
      also bound to cerebellar motilin receptors (pKd,hi = 7.29 and 8.91,
      respectively). Structure-activity studies with motilin fragments and the potency
      ranking of agonists suggest that a novel subtype receptor of motilin may exist in
      the brain. Guanosine 5'-O-(3-thiotriphosphate) (0.1 mM) reduced the number and
      the affinity for the high-affinity binding sites, which is evidence for G protein
      coupled receptors. Our findings open new perspectives for the study of the
      physiological role of motilin.

PMID- 9176205
TI  - Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric
      acid secretion in rats.
AB  - Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in
      medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The
      modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC
      induced stimulation of GAS was studied in urethan-anesthetized rats. The stable
      SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected
      unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to
      coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas
      DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS.
      DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into
      the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not
      the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345,
      injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8
      mumol/90 min) and potentiated the GAS response to kainic acid injected into the
      Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the
      DVC to reduce medullary TRH-induced stimulation of GAS in rats.

PMID- 9176207
TI  - Characterization of a beta 3-adrenoceptor stimulating gastrin and somatostatin
      secretions in rat antrum.
AB  - The beta 3-adrenoceptor (beta 3-AR) agonist SR-58611A {ethyl-[(7s)-7-[[(2R)-2-(3
      chlorophenyl)-2-hydroxyethyl]amino]5, 6,7,8-tetrahydronaphth-2-yl]oxyacetate
      hydrochloride} stimulated somatostatin and gastrin releases in isolated rat
      gastric antral epithelial cells. Stimulation was a concentration-dependent
      process with 50% effective concentrations of 2.7 +/- 1.1 and 3.8 +/- 1.9 nM
      compared with 209 +/- 71 and 230 +/- 51 nM for isoproterenol, respectively. It
      was inhibited by selective beta-AR antagonists with the following rank order of
      potency: SR-59230A 3-(2-ethylphenoxy)1-[(1S)-1,2,3,4-tetrahydronaphth- 1-ylamino]
      (2S)-2-propranol oxalate; beta 3-AR antagonist > ICI-118551[erythro-(+/-)-1-(7
      methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride; beta 2-AR
      antagonist > CGP-20712A[(+/-)-[2-(3-carbarmoyl-4-hydroxyphenoxy)-et hyl- amino]-3
      [4 (1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]- 2-propranol; beta 1-AR
      antagonist]. Furthermore, specific binding of 125I-cyanopindolol to the isolated
      cells was demonstrated and was displaced by the beta-AR antagonists according to
      the same rank order of potency and with apparent dissociation constants
      consistent with the 50% inhibitory concentrations for SR-58611A-stimulated
      somatostatin and gastrin releases. In addition, the presence of beta 3-AR mRNA
      was detected by reverse transcriptase polymerase chain reaction. These findings
      provide the first evidence for a gastric beta 3-AR mediating catecholamine
      stimulation of gastrin and somatostatin releases from antral cells.

PMID- 9176208
TI  - Acidosis induces hyperpermeability in Caco-2BBe cultured intestinal epithelial
      monolayers.
AB  - We previously demonstrated that ileal mucosal acidosis in pigs reversibly
      increases intestinal permeability to hydrophilic macromolecules, even in the
      absence of tissue hypoxia [A.L. Salzman, H. Wang, P.S. Wollert, T.J. Vandermeer,
      C.C. Compton, A.G. Denenberg, and M.P. Fink. Am. J. Physiol. 266 (Gastrointest,
      Liver Physiol, 29): G633-G646, 1994]. In an effort to further explore the
      mechanism(s) underlying this phenomenon, we examined the effect of acidic pH on
      the permeability characteristics of cultured Caco-2BBe (human intestinal
      epithelial) cells grown as monolayers on permeable supports. Permeability was
      determined by measuring the mucosal-to-basolateral flux of fluorescein disulfonic
      acid (FS; mol wt 478 Dal, fluorescein isothiocyanate-labeled dextran (FD4;
      average mol wt 4 kDa), or [3H]mannitol. Incubation of monolayers under
      hypercarbic conditions or with acidific bicarbonate-free medium significantly
      increased permeability to FS, FD4, and mannitol in a manner dependent on both
      time and pH. Incubation in medium at pH 5.43 for 24 h increased the release of
      lactate dehydrogenase and decreased the intensity of staining with calcein
      acetoxymethyl ester, findings that are indicative of plasma membrane injury;
      nevertheless, the percentage of nonviable cells did not increase. Ultrastructural
      analyses revealed evidence of increased paracellular trafficking of horseradish
      peroxidase after incubation of monolayers under acidic conditions. Fluorescence
      confocal microscopy and temperature studies demonstrated that incubation at pH
      5.43 induced an increase in both the intracellular uptake of FD4 and the
      activation energy for FS permeation across Caco-2BBe monolayers, respectively,
      suggesting increased transcellular permeation. Exposure to acidic conditions also
      decreased cellular levels of ATP. We conclude that acidosis increases both
      paracellular and transcellular permeability to hydrophilic macromolecules and
      leads to depletion of ATP.

PMID- 9176209
TI  - Patterns of gastric myoelectrical activity in human subjects of different ages.
AB  - The aim of this study was to investigate the developmental change of gastric
      myoelectrical activity in humans. Five groups of healthy subjects were studied,
      including 10 preterm newborns, 8 full-term newborns, 8 full-term infants (ages 2
      6 mo), 9 children (ages 4-11 yr), and 9 adults. Gastric myoelectrical activity
      was recorded using surface electrogastrography for 30 min before and 30 min after
      a test meal in each subject. Spectral analysis methods were applied to compute
      the parameters of the electrogastrogram (EGG). The results showed that the
      percentage of 2- to-4-cycles/min (cpm) slow waves was 26.6 +/- 3.9% in the
      preterm newborns, 30.0 +/- 4.0% in full-term newborns, 70 +/- 6.1% in 2- to 6-mo
      old infants (P < 0.001 compared with newborns), 84.6 +/- 3.2% in 4- to 11-yr-old
      children (P < 0.03 compared with infants), and 88.9 +/- 2.2% in the adults (P >
      0.05 compared with children). In conclusion, gastric slow waves are absent at
      birth, and there is a maturing process after birth. Age-matched controls are
      necessary for the interpretation of EGG data from neonates and infants, whereas
      EGG data in children are the same as in adults.

PMID- 9176211
TI  - Hypothalamic nitric oxide synthase is depressed in cholestatic rats.
AB  - We examined hypothalamic nitric oxide synthase (NOS) levels and release as well
      as steady-state mRNA levels in rats with cholestasis due to bile duct resection
      (BDR) and in sham-resected control rats. BDR rats had a significant reduction in
      hypothalamic NOS-containing neurons in the hypothalamic paraventricular nucleus
      as determined by NADPH-diaphorase staining, compared with sham-resected controls.
      In addition, NOS activity, measured indirectly by determining nitrite release
      from hypothalamic explants, was significantly lower in BDR rats compared with
      sham-resected animals. Hypothalamic steady-state NOS mRNA levels [brain
      constitutive NOS (bNOS)] were determined by semiquantitative reverse
      transcription-polymerase chain reaction and were found to be increased 1.5-fold
      in BDR rats compared with sham rats. In summary, BDR rats have diminished
      hypothalamic NOS levels and activity coupled with enhanced steady-state bNOS mRNA
      levels, suggesting that depressed hypothalamic NOS protein levels are due to
      posttranscriptional defects.

PMID- 9176210
TI  - Insights into human colonic physiology obtained from the study of flatus
      composition.
AB  - To better understand the physiology of colonic gas production, each flatus
      passage of 16 subjects over a 4-h period was analyzed by gas chromatography for
      N2, O2, H2, CO2, CH4, and for odoriferous sulfur-containing gases. Appreciable
      intraindividual and enormous interindividual variability was observed, indicating
      that each gas passage reflected the interaction of highly variable liberation
      and/or removal mechanisms. The predominant flatus gas was CO2, H2, and N2 in
      seven, six, and three subjects, respectively. Gases produced intraluminally (H2,
      CO2, and CH4) comprised approximately 74% of flatus, and rapid CO2 and H2
      productions were responsible for high passage rates. A positive correlation
      between flatus H2 and CO2 suggested that CO2, like H2, mainly was a bacterial
      product. Whereas methanogens and H2S-producing bacteria usually are mutually
      exclusive in feces, CH4 and H2S did not negatively correlate, indicating
      coexistence of both organisms in the colon. We conclude that analysis of flatus
      composition provides a novel means of assessing colonic physiology, particularly
      ongoing bacterial metabolism throughout the unperturbed colon.

PMID- 9176212
TI  - Regulation and translocation of ATP-dependent apical membrane proteins in rat
      liver.
AB  - The bile canalicular membrane contains four specific ATP-dependent transport
      processes that are involved in secretion of bile acids, non-bile acid organic
      anions (mrp1), phospholipids (mdr2), and organic cations (mdr3). The aim of this
      study was to determine how the canalicular presence of these transport proteins
      is regulated. Canalicular membrane vesicles (CMV) were prepared from livers of
      rats treated with taurocholate (TC) and/or dibutyryl-adenosine 3',5'-cycle
      monophosphate (DBcAMP) with and without pretreatment with colchicine. Transport
      studies were performed with radiolabeled substrates. Changes in the relative
      amounts of transport proteins were determined by Western blots. Compared with
      controls, the specific activity of each of the transport processes was enhanced
      1.5- and 3-fold with TC and DBcAMP treatments, respectively. Western blots
      revealed the same increases with mdr2 and mdr3. Pretreatment of rats with
      colchicine prevented these responses fully with TC treatment, whereas only
      partial prevention was obtained with DBcAMP treatment. Besides the ATP-dependent
      transporters, the relative specific activities of the canalicular membrane
      ectoenzyme markers, leucine aminopeptidase and gamma-glutamyltranspeptidase, were
      also affected the same way. These results suggest that TC and DBcAMP increase the
      specific activity of the canalicular ATP-dependent transport proteins and some
      canalicular membrane ectoenzymes by stimulating an increase in the relative
      amounts of these proteins in the membrane.

PMID- 9176213
TI  - The role of antioxidant enzymes in the control of opossum sphincter of Oddi
      motility.
AB  - Superoxide rapidly oxidizes nitric oxide (NO) to form peroxynitrite, thus
      terminating the biological activity of NO. The aims of our study were to
      determine if superoxide alters the motor function of the sphincter of Oddi and to
      localize the antioxidant enzymes in the sphincter of Oddi. Immunostaining was
      performed and enzyme activities were measured in the sphincter of Oddi. In
      physiological experiments, force-displacement transducers recorded tension in the
      spontaneously contracting sphincter of Oddi and after electrical field
      stimulation (EFS) of precontracted sphincter of Oddi. Superoxide was generated by
      the addition of xanthine with xanthine oxidase, superoxide radicals were
      scavenged by the addition of superoxide dismutase (SOD), and catalase or SOD was
      inhibited by diethyldithiocarbamic acid. Immunostaining demonstrated SOD and
      catalase immunoreactivity in ganglia situated at the serosal surface of the
      circular muscle. Total SOD activity was 202 +/- 12 U/mg. Generation of superoxide
      or inhibition of SOD increased the contractile frequency and decreased relaxation
      after EFS. We conclude that superoxide alters sphincter of Oddi motor function,
      and the presence of superoxide scavenging enzymes in enteric plexuses suggests
      that they may regulate sphincter of Oddi neuromuscular function by clearing
      endogenous superoxide.

PMID- 9176214
TI  - Function of upper esophageal sphincter during swallowing: the grabbing effect.
AB  - This study investigated deglutitive axial force developed within the pharynx,
      upper esophageal sphincter (UES), and cervical esophagus. Position and
      deglutitive excursion of the UES were determined using combined manometry and
      videofluoroscopy in eight healthy volunteers. Deglutitive clearing force was
      quantified with a force transducer to which nylon balls of 6- or 8-mm diameter
      were tethered and positioned within the oropharynx, hypopharynx, UES, and
      cervical esophagus. Axial force recordings were synchronized with
      videofluoroscopic imaging. Clearing force was dependent on both sphere diameter
      (P < 0.05) and location, with greater force exhibited in the hypopharynx and UES
      compared with the oropharynx and esophagus (P < 0.05). Within the UES, the onset
      of traction force coincided with passage of the pharyngeal clearing wave but
      persisted well beyond this. On videofluoroscopy, the persistent force was
      associated with the aboral motion of the ball caught within the UES. Force abated
      with gradual slippage of the UES around the ball. The force attributable to the
      combination of UES contraction and laryngeal descent was named the grabbing
      effect. The grabbing effect functions to transfer luminal contents distal to the
      laryngeal inlet at the end of the pharyngeal swallow, presumably acting to
      prevent regurgitation and/or aspiration of swallowed material.

PMID- 9176215
TI  - Large but not small intrahepatic bile ducts are involved in secretin-regulated
      ductal bile secretion.
AB  - We have shown that agonist-regulated ductal secretion is limited to large
      cholangiocytes. To directly study cholangiocyte heterogeneity along the length of
      the normal biliary tree, we defined the genetic and functional expression of
      agonist-induced ductal secretion in intrahepatic bile duct units (IBDU) of
      different sizes. Small IBDU (< 15-microns diam) were separated from large IBDU (>
      or = 15-microns diam), and then ducts of different sizes were characterized by
      morphometric analysis, gene expression, secretin-induced adenosine 3',5'-cyclic
      monophosphate (cAMP) synthesis, and secretion by change in luminal size in
      response to agonists. IBDU diameters ranged from 11 to 65 microns. Secretin
      increased ductal secretion solely in large IBDU. Forskolin induced a modest
      increase in ductal secretion in small IBDU but markedly increased ductal
      secretion in large IBDU. Secretion increased Cl-/HCO3- exchanger activity and
      cAMP levels in large but not small IBDU. Secretin receptor and Cl-/HCO3 exchanger
      mRNAs were detected only in large IBDU. We propose that agonist-induced ductal
      secretion occurs in large (> or = 15-microns diam) but not small (< 15-microns
      diam) intrahepatic ducts.

PMID- 9176216
TI  - Effects of transmural field stimulation in isolated smooth muscle of human rectum
      and internal anal sphincter.
AB  - Smooth muscle preparations from the circular muscle layer of the most distal
      rectum and the proximal and distal human internal anal sphincter (IAS) mounted in
      organ baths to record isometric tension developed spontaneous tension. Transmural
      electrical field stimulation (TMS) induced frequency- and impulse duration
      dependent relaxations sensitive to tetrodotoxin in the stimulation range of 0.5
      40 Hz and 0.04-0.6 ms. Poststimulus contractions were most frequent and prominent
      in rectal preparations. Maximal relaxations were comparable in the three
      locations and were achieved at 10 Hz and 0.4 ms. The frequency inducing half
      maximal response was lower in rectal strips compared with IAS. Phentolamine (10
      (6) M) enhanced relaxations and diminished off-contractions at 40 Hz in distal
      IAS. N omega-nitro-L-arginine (L-NNA) concentration dependently inhibited both
      relaxations and off-contractions (10 Hz, 0.4 ms). The pD2 values (-log EC50) of L
      NNA were lower in rectal muscle compared with those in IAS. L-Arginine (10-(4) M)
      inhibited the blocking effect of L-NNA. In one-half of the preparations, L-NNA
      reversed the relaxations to duration contractions (15-40 Hz), which were
      inhibited by atropine in rectal preparations and by phentolamine in IAS. In
      conclusion, excitatory innervation of the IAS is alpha-adrenergic and cholinergic
      in the rectum. A product of the L-arginine-nitric oxide pathway mediates the TMS
      induced inhibition of the muscle and is also involved in poststimulus
      contractions.

PMID- 9176217
TI  - Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed a
      protein-restricted diet.
AB  - Hepatic enzymes associated with glucose hemostasis were studied in offspring of
      dams fed either a 20% protein (control) or an isocaloric 8% protein (low-protein)
      diet during pregnancy and lactation. Additionally, offspring were exposed to
      maternal 8% protein diet only during gestation (recuperated) or lactation
      (postnatal low-protein). Glucokinase activity decreased (approximately 50%),
      whereas phosphoenolpyruvate carboxykinase (PEPCK) activity increased
      (approximately 100%), in the low-protein and recuperated offspring compared with
      controls (P < 0.001) at 21 days of age. However, the postnatal low-protein
      offspring had enzyme activities comparable with those of controls. These changes
      were still evident in 11-mo-old offspring weaned onto a normal laboratory chow.
      Parallel changes were apparent in mRNA levels of glucokinase and PEPCK in the low
      protein male offspring. Thus the effect of programming metabolism extends not
      only to protein biochemistry but possibly also to the regulation of gene
      expression. Furthermore, these changes could not be attributed to glucagon or
      insulin, because ratios of these hormones were comparable between the control and
      low-protein groups.

PMID- 9176218
TI  - Characterization of sphingosine 1-phosphate-induced actions and its signaling
      pathways in rat hepatocytes.
AB  - Sphingosine 1-phosphate (S-1-P) and lysophosphatidic acid (LPA) stimulated
      glycogen phosphorylase, a rate-limiting enzyme responsible for glycogenolysis, in
      association with Ca2+ mobilization and phospholipase C (PLC) activation in rat
      hepatocytes. S-1-P, but not LPA, also inhibited adenosine 3',5'-cyclic
      monophosphate accumulation reflecting adenylyl cyclase inhibition. S-1-P-induced
      PLC activation, Ca2+ mobilization, and phosphorylase activation were markedly
      enhanced by primary culture of the cells for 24 h, whereas the inhibitory
      adenosine 3',5'-cyclic monophosphate response was unchanged by increasing culture
      time. Activation of the PLC-Ca2+ system during primary culture was specific to
      the lysosphingolipid; PLC and Ca2+ responses to LPA and NaF were unchanged or
      slightly attenuated by increasing culture time. Pertussis toxin treatment almost
      completely suppressed the S-1-P-induced inhibition of adenylyl cyclase but hardly
      influenced the lipid-induced activation of PLC and its cascade reactions. We
      conclude that S-1-P, through an LPA receptor-independent mechanism, stimulates
      two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of
      adenylyl cyclase, through distinct S-1-P receptor-transducer systems, resulting
      in the modulation of glycogenolysis in rat hepatocytes.

PMID- 9176219
TI  - GH elevates serum IGF-I levels but does not alter mucosal atrophy in parenterally
      fed rats.
AB  - Growth hormone (GH) action is primarily mediated by insulin-like growth factor I
      (IGF-I), although both growth factors show tissue-selective effects. We
      investigated the effects of GH, IGF-I, and GH plus IGF-I on jejunal growth and
      function in rats maintained with total parenteral nutrition (TPN) and given
      recombinant human GH (rhGH) (400 micrograms/day sc, twice daily) and/or rhIGF-I
      (800 micrograms/day in TPN solution) for 5 days. Administration of GH or IGF-I
      alone produced similar increases in serum IGF-I levels and body weight; GH plus
      IGF-I further increased these parameters. TPN reduced mucosal mass, protein and
      DNA content, villus height, crypt depth, and enterocyte migration rate. IGF-I or
      GH plus IGF-I produced equivalent increases in all intestinal growth parameters;
      GH alone had no effect. GH, IGF-I, or GH plus IGF-I reduced TPN-induced increases
      in sucrase-specific activity. IGF-I, but not GH, attenuated TPN-induced increases
      in tissue conductance and carbachol-stimulated ion secretion. In contrast to IGF
      I, GH does not stimulate intestinal growth during TPN and has less effect on
      normalizing TPN-induced changes in epithelial function.

PMID- 9176220
TI  - Bile salt-induced apoptosis of hepatocytes involves activation of protein kinase
      C.
AB  - Toxic bile salts induce hepatocyte apoptosis, a model relevant to liver injury
      during cholestasis. However, the signaling mechanisms culminating in bile salt
      induced apoptosis remain unclear. Because protein kinase C (PKC) is activated by
      bile salts in hepatocytes and causes apoptosis in other cells, we tested the
      hypothesis that bile salt-induced hepatocyte apoptosis is mediated by PKC. The
      PKC inhibitors chelerythrine and Go-6976 reduced, whereas a PKC agonist, phorbol
      12-myristate 13-acetate (PMA), increased glycochenodeoxycholate (GCDC)-induced
      hepatocyte apoptosis. Membrane-associated total PKC activity was increased in
      GCDC-treated hepatocytes. Quantitative immunoblot analysis demonstrated membrane
      translocation of PKC-alpha, PKC-delta, and PKC-epsilon to hepatocyte membranes
      after administration of GCDC. Direct activation of PKC-alpha and PKC-delta by
      GCDC was also demonstrated using recombinant, baculovirus-expressed PKC isoforms
      in a medium of defined lipid composition. Chelerythrine and Go-6976 reduced,
      whereas PMA enhanced, cathepsin B activity during treatment of hepatocytes with
      GCDC, demonstrating coupling of PKC activity to the protease effector mechanisms
      of apoptosis. In conclusion, our data suggest for the first time that PKC
      dependent signaling pathways play a critical role in bile salt-induced hepatocyte
      apoptosis.

PMID- 9176221
TI  - Effect of hyperglycemia on gastric acid secretion during the gastric phase of
      digestion.
AB  - We have examined the effect of an acute stable hyperglycemia on gastric acid
      secretion during the gastric phase of digestion. Gastric acid output was measured
      with a recovery marker (phenol red) under basal conditions and after repeated
      intragastric instillation of a liquid meal in seven healthy subjects on two
      separate occasions: during normoglycemia (serum glucose, 15 mM). Premeal gastric
      acid output was significantly (P < 0.05) reduced during hyperglycemia compared
      with during normoglycemia (2.6 +/- 1.0 vs. 5.8 +/- 1.8 mmol/h). Intragastric meal
      stimulated incremental acid output during hyperglycemia was significantly (P <
      0.05) reduced compared with during normoglycemia (19 +/- 4 vs. 38 +/- 9 mmol/120
      min). Meal-stimulated gastrin release during hyperglycemia was significantly (P <
      0.05) reduced compared with that during normoglycemia (4.9 +/- 1.3 vs. 6.6 +/-
      1.6 micrograms.1(-1).120 min-1). The intragastric meal induced significant (P <
      0.05) increases in pancreatic polypeptide concentrations only during
      normoglycemia. During hyperglycemia, recovery rates of gastric contents were
      significantly (P < 0.05) increased compared with during normoglycemia, both
      before (81 +/- 4 vs. 71 +/- 6%) and after (72 +/- 4 vs. 57 +/- 4%) meal
      ingestion, pointing to delayed gastric emptying of liquids during hyperglycemia.
      In conclusion, 1) gastric acid secretion under unstimulated conditions and during
      the gastric phase of digestion is reduced during hyperglycemia; 2) meal
      stimulated gastrin release is significantly reduced during hyperglycemia; 3) the
      reduction in meal-stimulated acid output is correlated with the reduction in
      gastrin releases; and 4) pancreatic polypeptide secretion is significantly
      reduced during hyperglycemia, pointing to impaired vagal cholinergic tone.

PMID- 9176222
TI  - ME-3407, a new antiulcer agent, inhibits acid secretion by interfering with
      redistribution of H(+)-K(+)-ATPase.
AB  - ME-3407 is a newly developed antiulcer drug that markedly promoted the healing of
      acetic acid-induced chronic ulcers in rats presumably due to potent inhibition of
      acid secretion. ME-3407 and its metabolites, the sulfoxide of which was
      preserved, produced dosedependent inhibition of aminopyrine accumulation by
      rabbit gastric glands stimulated by any agonist, suggesting that the site of
      their action was downstream from the production of second messengers. Although
      one of the metabolites, EF-4025, showed some inhibitory effects on functional
      activities of H(+)-K(+)-ATPase, ME-3407 itself was not a proton pump inhibitor.
      ME-3407, but not omeprazole, inhibited the stimulation-associated redistribution
      of H(+)-K(+)-ATPase from microsomes into the apical membranes in addition to
      delocalizing ezrin, a putative F-actin-membrane linker, from apical plasma
      membrane. ME-3407 and EF-4025 inhibited myosin light chain kinase (MLCK) and
      protein kinase A activities. Because another MLCK inhibitor, wortmannin, showed
      the same properties as ME-3407, i.e., inhibition of aminopyrine accumulation,
      inhibition of stimulation-associated redistribution of H(+)-K(+)-ATPase, and
      abnormal distribution of ezrin, we hypothesize that MLCK is one of the potential
      targets for the drug. We conclude that ME-3407 is a promising drug for treating
      peptic ulcers, as well as a useful tool for studying mechanisms of parietal cell
      activation, especially related to the recruitment and recycling of the proton
      pump.

PMID- 9176223
TI  - Interleukin-4 modulates cholinergic neural control of mouse small intestinal
      longitudinal muscle.
AB  - Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and
      causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are
      spasmogenic, potentially causing parasitic expulsion, we investigated the effect
      of interleukin-4 on smooth muscle and the mast cell and mediator dependency of
      this effect. BALB/c, mast cell-deficient W/Wv mice, 5-lipoxygenase-efficient
      mice, and their littermate controls were injected with interleukin-4-anti
      interleukin-4 antibody complexes that chronically increase serum interleukin-4
      levels. Mid-small intestinal segments, hung longitudinally in organ baths, were
      stimulated electrically or by agonists. The cholinergic response to electrical
      field stimulation was significantly increased by interleukin-4 treatment in
      BALB/c but not W/Wv mice. The enhanced cholinergic contraction was not due to
      increased acetylcholine responsiveness but was dependent on leukotriene D4, since
      it was reversed by leukotriene D4 receptor antagonism, and not observed in 5
      lipoxygenase knock-out mice. Leukotriene D4 responsiveness was unaffected by
      interleukin-4 treatment. We conclude that interleukin-4 amplifies cholinergic
      excitation through a mast cell and leukotriene D4-dependent mechanism.

PMID- 9176224
TI  - Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty
      acid beta-oxidation.
AB  - Glucocorticoid administration may produce fatty liver in humans. We investigated
      the effects of dexamethasone on hepatic mitochondria and lipid metabolism in
      mice. Dexamethasone 21-phosphate (20 microM) did not inhibit the mitochondrial
      inner membrane-bound very-long-chain acyl-CoA dehydrogenase but inhibited the
      matrixlocated long-, medium-, and short-chain dehydrogenases. Dexamethasone 21
      phosphate (20 microM) inhibited the first beta-oxidation cycle of [1
      (14C)]butyric acid and [1-(14C)]octanoic acid but not that of [1-(14C)]palmitic
      acid. Administration of dexamethasone 21-phosphate (100 mg/kg) decreased the in
      vivo oxidation of [1-(14C)]butyric acid and [1-(14C)]octanoic acid into [14C]CO2
      but not that of [1-(14C)]palmitic acid and decreased the hepatic secretion of
      triglycerides. After 5 days of treatment (100 mg/kg daily), hepatic triglycerides
      were increased and both microvesicular steatosis and ultrastructural
      mitochondrial lesions were present. In conclusion, glucocorticoids inhibit medium
      and short-chain acyl-CoA dehydrogenation and hepatic lipid secretion in mice.
      These effects may account for their steatogenic effects in humans.

PMID- 9176225
TI  - Characterization of proteases and protease inhibitors in the rat stomach.
AB  - Previously our laboratory reported increased activity of the thiol proteinase
      cathepsin B in gastric juice after ethanol-induced mucosal injury. In this study
      we measured proteinase activity (PA) and proteinase inhibitory activity (PIA)
      with the general substrates hemoglobin, azocasein, and bovine serum albumin (BSA)
      at optimal pH (2.0, 5.6, and 7.4) of aspartic, cysteine, and serine proteinases.
      Homogenates of glandular stomach mucosa and gastric juice from fasted rats were
      incubated in the presence or absence of specific inhibitors and sulfhydryl (SH)
      alkylators N-ethylmaleimide and iodoacetate. PIA was measured after acid and heat
      inactivation of endogenous proteinases and addition of 20 micrograms/ml pepsin,
      20 or 100 micrograms/ml thiol proteinase papain, or 20 micrograms/ml trypsin for
      5 min before digestion at 37 degrees C. The highest proteolytic activity was
      found at pH 2.0 (pepsin) in juice and mucosal homogenate, but proteases were also
      found at pH 5.6 and 7.4, where pepsin was inactive. Pepstatin inhibited most
      proteolytic activity at pH 2.0. The SH protease inhibitor leupeptin diminished PA
      mainly at pH 5.6. N-ethylmaleimide or iodoacetate substantially reduced the PA in
      acidic milieu, with maximum effect at pH 5.6. Endogenous PIA, expressed as
      inhibition of the effect of 1 microgram of pepsin, papain, and trypsin on BSA,
      was 13.1, 1.4, and 9.2% in gastric mucosa and 15.3, 22.5, and 6.2% in gastric
      juice at pH 2.0, 5.6, and 7.4, respectively. We have concluded that 1) endogenous
      proteinases and inhibitors in rat stomach can be measured using BSA and
      hemoglobin as substrates, 2) of the proteinases found in the stomach, 98% was
      pepsin at pH 2.0 and up to 27% or 17% was SH sensitive at pH 5.6 or 7.4,
      respectively, and 3) proteinases and their specific endogenous inhibitors may
      play a role in gastric mucosal injury and protection.

PMID- 9176226
TI  - Correlation and comparison of magnetic and electric detection of small intestinal
      electrical activity.
AB  - The small intestinal basic electrical rhythm (BER) was detected simultaneously
      with serosal electrodes and a transabdominal superconducting quantum interference
      device (SQUID) magnetometer in anesthetized rabbits. We induced mesenteric
      ischemia to correlate serosal electrode recording of changes in BER with the
      SQUID magnetometer. The BER frequency was obtained by spectral analysis of the
      data using Fourier and autoregressive techniques. There was a high degree of
      correlation (r = 0.96) between the BER frequency determined using the serosal
      electrodes and the BER frequency ascertained from SQUID data. Additionally, the
      effects of an electrical insulator on the external electric and magnetic fields
      were studied in the rabbit model. The presence of an insulator profoundly
      attenuates external electric potentials recorded by cutaneous electrodes but does
      not significantly affect external magnetic fields or serosal potentials. We
      conclude that SQUID magnetometers could noninvasively record small intestinal BER
      that was highly correlated with the activity recorded by invasive serosal
      electrodes. The advantages of magnetic field measurements have encouraged us to
      investigate clinical applications.

PMID- 9176227
TI  - Kinetic and molecular identification of sodium-dependent glucose transporter in
      normal rat cholangiocytes.
AB  - While previous work has demonstrated that monosaccharides can be absorbed from
      bile, studies of sugar transport by the biliary, epithelia (i.e., cholangiocytes)
      are lacking. Using a novel model of polarized rat cholangiocytes in primary
      culture, designated normal rat cholangiocytes (NRC), we examined directly the
      uptake and transcellular transport of a nonmetabolizable monosaccharide, methyl
      alpha-D-glucopyranoside (AMG). When the apical or basolateral domain of
      cholangiocytes was exposed to radiolabeled AMG or sucrose (control), only apical
      absorption of AMG was evident. This apical uptake was time dependent, saturable,
      and significantly inhibited (> or = 90%) by removal of Na+ or in the presence of
      phlorizin (0.1 mM), a competitive inhibitor of the Na(+)-glucose cotransporter.
      The transcellular flux of AMG was also polar (i.e., apical to basolateral).
      Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of
      the transcript for the specific Na(+)-glucose cotransporter SGLT1 in NRC and in
      freshly isolated cholangiocytes but not in purified hepatocytes; in contrast, the
      transcript for SGLT2 was absent in all liver samples. In situ RT-PCR on frozen
      sections of normal rat liver showed that SGLT1 was expressed exclusively in
      cholangiocytes. Immunoblot analysis using a specific polyclonal antibody for the
      facilitative glucose transporter GLUT1 demonstrated it to be present in vesicles
      derived from NRC enriched in basolateral plasma membrane domains. Our data are
      consistent with the concept that SGLT1 is present on the apical domain of biliary
      epithelia and, in conjunction with GLUT1 on the basolateral domain, accounts for
      glucose absorption from bile.

PMID- 9176228
TI  - Endothelin-activated calcium signaling in enteric glia derived from neonatal
      guinea pig.
AB  - The ability of guinea pig enteric glia to respond to endothelins was examined
      using fura 2-based digital microscopy in glial cells derived from guinea pig
      taenia coli. Each isoform of endothelin (ET-1, ET-2, ET-3) evoked dose-dependent
      and equipotent increases in intracellular Ca2+ concentration ([Ca2+]i) and in
      percentage of cells responding, 4alaEt-1, an ETB receptor agonist, elicited
      similar [Ca2+]i increments. BQ-788, an ETB antagonist, inhibited [Ca2+]i
      responses to endothelin. Preincubation of glia with U-73122 a phospholipase C
      inhibitor, abolished the [Ca2+]i response to ET-3 exposure. Thapsigargin also
      eliminated ET-3-evoked Ca2+ signaling. The inositol 1,4,5-trisphosphate (IP3)
      receptor antagonist heparin, introduced into glial cells by radio frequency
      electroporation, blocked [Ca2+]i responses to ET-3 (100 nM) in 63% of glia.
      Sustained elevation in [Ca2+]i was abolished by removal of Ca2+ from the buffer
      and inhibited 85. -3% by Ni2+ (1 mM). Preincubation of glia with 100 nM phorbol
      12-myristate 13-acetate (24 h) also inhibited sustained increments in [Ca2+]i by
      87%. The presence of IP3 receptors in enteric glia was confirmed by
      immunofluorescent confocal microscopy.

PMID- 9176229
TI  - Female rats exhibit greater susceptibility to early alcohol-induced liver injury
      than males.
AB  - It is known that women develop hepatic injury more rapidly and with exposure to
      less ethanol than men; however, mechanisms remain unclear. The purpose of this
      study was to determine if an enteral alcohol delivery model could be used to
      study susceptibility of females to alcohol-induced liver injury. Male and female
      Wistar rats (age- or weight-matched) were given ethanol (11-12 g.kg-1.day-1)
      continuously for up to 4 wk via intragastric feeding, and control rats received a
      high-fat diet without ethanol. There were no significant differences in body
      weight among the groups studied. Furthermore, mean ethanol concentrations, their
      cyclic pattern in urine, and rates of ethanol elimination were also not different
      between the genders under these conditions. Ethanol treatment elevated serum
      aspartate aminotransferase levels in male rats to 126 +/- 10 IU/l after 4 wk. In
      females, however, values increased more rapidly and reached significantly higher
      values at 4 wk (168 +/- 18 IU/l). Steatosis, inflammation, and necrosis assessed
      histologically also developed more rapidly and were more severe in females than
      males. Steatosis due to ethanol exposure, which was localized in centrilobular
      areas in males, was panlobular in the female. Moreover, endotoxin in plasma,
      intercellular adhesion molecule 1 expression in hepatic sinusoidal-lining cells,
      and the number of infiltrating inflammatory cells in the liver were 2-2.5-fold
      greater in females than males. These changes possibly account for increased
      hepatic injury due to ethanol in the female.

PMID- 9176230
TI  - Neutrophil margination and extravasation in sinusoids and venules of liver during
      endotoxin-induced injury.
AB  - Neutrophils contribute to liver damage during endotoxin shock. The objective of
      this investigation was to document where neutrophils localize in the hepatic
      vasculature and whether they migrate out of sinusoids or postsinusoidal venules.
      A well-characterized model of galactosamine and endotoxin shock and
      immunostaining for neutrophil-associated migration inhibition factor-related
      protein complex 8/14 S100 calcium-binding proteins were used. Treatment of
      C3Heb/FeJ mice with 100 micrograms/kg Salmonella abortus equi endotoxin alone or
      in combination with 700 mg/kg galactosamine induced a time-dependent increase of
      neutrophil margination in sinusoids and postsinusoidal venules at 4 h. The number
      of venular neutrophils decreased in both groups at later time points without
      evidence for transmigration. Extravasation of neutrophils was only observed from
      sinusoids in galactosamine plus endotoxin-treated animals between 4 and 7 h,
      which correlated with parenchymal cell injury. After endotoxin alone, large
      numbers of neutrophils remained sequestered in sinusoids without injury. These
      data suggest that neutrophils cause hepatocellular injury during endotoxemia
      after extravasation and are less likely to cause damage when sequestered in the
      vasculature. In the liver, neutrophils migrate out of sinusoids and not out of
      postsinusoidal venules.

PMID- 9176231
TI  - Interleukin-15 signals T84 colonic epithelial cells in the absence of the
      interleukin-2 receptor beta-chain.
AB  - Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2)
      due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta
      chain and the common gamma-chain receptor in addition to one other IL-15 binding
      receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required
      to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial
      cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We
      report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase
      polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL
      15 fusion protein in immunoperoxidase and flow cytometric experiments. In
      addition, IL-15, but not IL-2, accelerates and enhances the development of
      transepithelial resistance across T84 monolayers in a dose-dependent fashion. We
      conclude that normal and T84 colonic epithelial cells express IL-15R alpha and
      are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in
      the absence of IL-2R beta-chain in T84 cells.

PMID- 9176232
TI  - Gastric epithelial morphogenesis in normal and transgenic mice.
AB  - The epithelium located in the corpus of the adult mouse stomach forms mucosal
      invaginations known as gastric units. Gastric units are populated by members of
      the pit, parietal, and neck-zymogenic cell lineages all of which are derived from
      multipotent stem cells. Gastric unit morphogenesis was examined in normal
      embryonic day 18 (E18) to postnatal day 28 (P28) FVB/N mice with electron
      microscopy and multilabel immunohistochemistry. E18 units appear as short, solid
      infoldings (primordial buds), 92% of whose cells represent pit, parietal, and
      neck cell precursors. Although the total number of cells per bud does not change
      from P1 to P7, immature cells decrease to 22% as differentiated pit, neck, and
      parietal cells appear. From P7 to P15, lineage precursors and their
      differentiated progeny increase and buds elongate. Between P15 and P21 the
      multipotent stem cell and its descendants are assembled into a distinct
      proliferative zone (isthmus) located in the midportion of each unit, and cellular
      migration-differentiation programs become compartmentalized. To examine the role
      of parietal cells in regulating gastric unit morphogenesis, nucleotides -1035 to
      +24 of the mouse H(+)-K(+)-adenosinetriphosphatase beta-subunit gene were used to
      express simian virus 40 large T antigen (SV40 TAg) exclusively in this lineage.
      SV40 TAg amplified the normally rare pre-parietal cell and disclosed a pre
      parietal cell precursor. Pre-parietal cells and their precursors were the
      predominant cells in E18-P1 transgenic buds. At later stages of development (P1
      P28) there was a block in differentiation of pre-parietal to mature parietal
      cells, a decrease in neck cells, and a marked depletion of zymogenic cells. These
      findings suggest that members of the parietal cell lineage are the source of
      instructions that affect the neck-zymogenic cell lineage, even before the gastric
      unit is compartmentalized into its anatomically distinct pit, isthmus, neck, and
      base regions.

PMID- 9176233
TI  - Hindbrain effects of PACAP on gastric motor function in the rat.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive
      cell bodies and fibers are visualized in hindbrain nuclei that are involved in
      the regulation of autonomic function, yet little is known about the gastric and
      cardiovascular effects of this peptide in the dorsal vagal complex, nucleus raphe
      obscurus, and nucleus ambiguus. Therefore, multiple-barreled micropipettes were
      used to inject PACAP-38 (1-100 pmol) into each of these nuclei in alpha
      chloralose anesthetized rats, while intragastric pressure, pyloric and greater
      curvature smooth muscle contractile activity, blood pressure, and heart rate were
      recorded. For comparison, the effect of L-glutamate (15 nmol) microinjected into
      the same sites on gastric motor activity was also assessed. L-Glutamate
      microinjected into each nucleus before PACAP-38 significantly increased
      intragastric pressure, both in terms of the peak increase and the total area of
      the response. Microinjections of PACAP-38 (10 and 100 pmol) into each of the
      nuclei significantly increased peak intragastric pressure, but the total area of
      the response was only significantly increased by the highest dose (100 pmol) in
      the case of the dorsal vagal complex and nucleus raphe obscurus. No consistent
      changes in heart rate and mean arterial blood pressure were noted after
      microinjection of PACAP-38 into each of the three nuclei. Bilateral vagotomy
      abolished the increase in intragastric pressure in response to microinjection of
      PACAP-38 into the dorsal vagal complex and nucleus raphe obscurus. We conclude
      that PACAP-38 in the dorsal vagal complex and nucleus raphe obscurus is involved
      in vagally mediated gastric motor excitation.

PMID- 9176234
TI  - Regulation of superoxide dismutase in primary cultures of rat colonic smooth
      muscle cells.
AB  - We have observed a rapid induction of manganese superoxide dismutase (MnSOD) in
      epithelial, neuronal, and smooth muscle cells (SMC) after acetic acid-induced
      colitis. To examine the regulation of MnSOD in the SMC more specifically, primary
      cultures of colonic SMC were developed by enzymatic digestion of the circular
      muscle layer from an adult rat. SMC were treated for 2-72 h with 0.5 microgram/ml
      Escherichia coli endotoxin [lipopolysaccharide (LPS)], 10 ng/ml tumor necrosis
      factor (TNF)-alpha, or 2 ng/ml interleukin-1 beta (IL-1 beta). Cotreatments were
      performed with IL-1 beta and 4 microM actinomycin or 50 microM cycloheximide.
      Northern analysis demonstrated 23-fold, 8-fold, and 6-fold inductions of MnSOD
      mRNA by IL-1 beta, LPS, and TNF-alpha, respectively. Induction of MnSOD by IL-1
      beta was eliminated by actinomycin but not by cycloheximide, implicating a
      requirement for de novo transcription. Western analysis resulted in a 23.7-fold
      induction of MnSOD protein after 48-h treatment with IL-1 beta. Induction of
      MnSOD by IL-1 beta and other inflammatory mediators may serve as a protective
      mechanism to reduce oxygen free radical- and nitric oxide-mediated cell damage
      during inflammation.

PMID- 9176235
TI  - Candidate canine enterogastrones: acid inhibition before and after vagotomy.
AB  - The relative contributions of several gut-derived peptides as enterogastrones
      known to be released in response to a fatty meal and to inhibit acid secretion
      have not previously been compared directly. We determined the acid-inhibitory
      activities of increasing intravenous doses of several peptides before and after
      highly selective vagotomy (HSV) during intragastric titration of a peptone meal
      in dogs. Before HSV, threshold inhibitory doses of peptide YY (PYY),
      cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg-1.h-1,
      respectively, whereas neurotensin, glucagon-like peptide-1 (GLP-1), and
      oxyntomodulin failed to inhibit acid secretion at doses up to 1,000 pmol.kg-1.h
      1. The calculated dose producing 50% acid inhibition (ID50) of secretin (62
      pmol.kg-1.h-1) was one-half that of PYY (128 pmol.kg-1.h-1). Maximal (90%) acid
      inhibition was produced by 100 pmol.kg-1.h-1 secretin and 500 pmol.kg-1.h-1 PYY.
      The highest dose of CCK that did not cause vomiting (100 pmol.kg-1.h-1) inhibited
      peptone-stimulated acid output by only 60%. After HSV, 500 pmol.kg-1.h-1. PYY and
      200 pmol.kg-1.h-1 CCK failed to inhibit acid output by more than 50%. Threshold
      doses for inhibition by PYY and CCK were 200 and 100 pmol.kg-1.h-1, respectively.
      Secretin remained a potent inhibitor after HSV, with an ID50 of 80 pmol.kg-1.h-1
      and a threshold dose of 10 pmol.kg-1.h-1. HSV also failed to affect inhibition
      caused by somatostatin. This study has shown that PYY and secretin are somewhat
      more potent and efficacious inhibitors of acid secretion than CCK but that all
      three peptides are far more active than GLP-1, neurotensin, and oxyntomodulin.
      PYY and CCK inhibit acid secretion in large part through vagal innervation of the
      gastric fundus, but the inhibitory effects of secretin are independent of fundic
      vagal innervation.

PMID- 9176236
TI  - Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats.
AB  - Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in
      vivo, intact, anesthetized rat model, we studied the role of
      gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine
      and somatostatin during intragastric stimulation of acid secretion during a
      peptone meal. In pylorusligated, adult male rats (each implanted with a gastric
      cannula and portal venous and splenic artery catheters), after a 30-min basal
      period, gastric acid secretion was stimulated for 90 min either by an intravenous
      infusion of gastrin-17 (15 micrograms.kg-1.h-1) or by extragastric titration of 5
      ml 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous
      plasma gastrin, histamine, and somatostatin concentrations were measured before
      and after close-arterial injection of a new, relatively selective, gastrin/CCK-B
      receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not
      basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X
      reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and
      plasma somatostatin by 34%. During intragastric peptone meal stimulation
      GR143330X reduced the acid response by 42% during the 30- to 60-min period but
      not during the 60- to 90-min period. GR143330X reduced the plasma histamine
      response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during
      the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block
      the gastrin response to peptone at any time. These results indicate that
      GR143330X is an effective agent for blocking gastrin-stimulated acid secretion
      and histamine and somatostatin release in rats. Furthermore, we show for the
      first time in an intact, in vivo, anesthetized rat model that meal-stimulated
      activation of gastrin/CCK-B receptors stimulates acid secretion in part by
      regulating the release of histamine and somatostatin.

PMID- 9176237
TI  - Taurochenodeoxycholic acid ameliorates and ursodeoxycholic acid exacerbates small
      intestinal inflammation.
AB  - Intraluminal bacteria, food intake, and bile play important roles in indomethacin
      induced small intestinal inflammation in rats. Tauroursodeoxycholic acid (TUDCA)
      and ursodeoxycholic acid (UDCA) inhibit hydrophobic bile acid-induced damage in
      various types of cells. We investigated the effects of these bile acids along
      with the possible influence of other bile acids on this model of inflammation.
      Clinical and intestinal inflammatory parameters and bile secretion were assessed
      after 7-day dietary bile acid pretreatments and subsequent indomethacin
      injections. UDCA significantly enhanced indomethacin-associated reductions in
      food intake and body weight, increases in gross inflammatory scores and
      myeloperoxidase activity, and the shortening of small intestinal length.
      Taurochenodeoxycholic acid (TCDCA) significantly normalized the clinical
      inflammatory parameters, prevented indomethacin-induced increases in the biliary
      contents of secondary bile acids and hydrophobicity index, and tended to
      attenuate the intestinal inflammation. Although elevated biliary levels of
      muricholic acids and a decreased hydrophobicity index were evident before
      indomethacin injection in the TCDCA case, these alterations could not explain the
      TCDCA-mediated protection. Dietary TCDCA attenuates whereas UDCA exacerbates
      intestinal inflammation in this model. Alterations in the bile composition
      (increases in UDCA and chenodeoxycholic acid) may explain the observed
      modification effects.

PMID- 9176238
TI  - Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea
      pig ileum.
AB  - Intestinal motility disorders are often associated with gut inflammation. We
      evaluated, in vitro under isometric conditions, changes in contractility of
      longitudinal and circular muscle layers from guinea pig ileum after 2,4,6
      trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not
      modify length-active tension relationships for both muscle layers, whereas a
      significant increase in passive tension was observed in the circular muscle
      response to stretching. Moreover, in both control and inflamed strips at optimal
      stretch, concentration-response curves to KCl were similar for both layers. In
      contrast, contractile responses to receptor agonists were differentially altered
      in both layers in comparison with controls. Thus, in longitudinal strips from
      TNBS-treated ileum, there was a twofold increase in maximal response (Emax)
      induced by carbachol and histamine without modification of 50% effective
      concentration (EC50) values; responses to 5-hydroxytryptamine (5-HT) were not
      modified; both alpha 1- and alpha 2-adrenoceptor-mediated responses to
      epinephrine were abolished. In circular strips, inflammation did not affect the
      Emax induced by carbachol and histamine but led to increased EC50 values; Emax to
      5-HT was reduced without change in EC50 values. Moreover, in the dose range used
      (0.1 nM to 0.1 mM), a maximal response to carbachol was not obtained in inflamed
      circular strips. The results indicate that in the guinea pig model of TNBS
      induced ileitis, the in vitro contractile responses of circular and longitudinal
      smooth muscle to the stimulation of various receptors are differentially altered,
      whereas non-receptor-mediated contraction to KCl depolarization is not modified.

PMID- 9176239
TI  - Endogenous carbon monoxide suppression stimulates bile acid-dependent biliary
      transport in perfused rat liver.
AB  - This study aimed to investigate whether carbon monoxide (CO), a product of heme
      oxygenase that degrades protoheme IX, serves as an endogenous modulator for
      biliary transport. To that end, effects of zinc protoporphyrin IX (ZnPP), a heme
      oxygenase inhibitor, on the biliary transport were tested in perfused rat liver.
      Perfusion of 1 microM ZnPP abolished detectable levels of CO in the venous
      perfusate and increased bile acid-dependent bile output accompanying an increased
      secretion of bile salts. The ZnPP-induced choleresis coincided with a reduction
      of tissue guanosine 3',5'-cyclic monophosphate (cGMP) levels and a decrease in
      vascular conductance. On administration of 2.5 microM CO, ZnPP-elicited
      choleresis, decreases in vascular conductance, and cGMP levels were all
      attenuated. Treatment with 1 microM 8-bromoguanosine 3',5'-cyclic monophosphate
      (8-BrcGMP) partly attenuated the ZnPP-induced choleresis in concert with
      repression of vascular conductance. Furthermore, treatment of the liver with
      methylene blue, a guanylate cyclase inhibitor, evoked a choleresis similar to
      that induced by ZnPP. Thus endogenous CO suppression stimulates the biliary
      transport in part through a cGMP-dependent mechanism.

PMID- 9176240
TI  - Epidermal growth factor activates phospholipase C-gamma 1 via G(i)1-2 proteins in
      isolated pancreatic acinar membranes.
AB  - In the present study, isolated pancreatic acinar membranes were used to
      investigate the mechanism of epidermal growth factor (EGF)-induced activation of
      phospholipase C (PLC). The data show that EGF caused a rapid and strong increase
      in tyrosine phosphorylation of the EGF receptor, with a maximum 5-15 s after the
      beginning of the incubation followed by a decline. With use of
      [3H]phosphatidylinositol 4,5-bisphosphate as an exogenous substrate, PLC activity
      increased fourfold on exposure of the membranes to EGF (85 nM). In contrast, EGF
      induced tyrosine phosphorylation of PLC-gamma 1 was rather small, indicating that
      tyrosine phosphorylation of PLC-gamma 1 is not proportional to changes in PLC
      activity. EGF-induced activation of PLC was strongly inhibited by pretreatment of
      the membranes with pertussis toxin, by an antibody raised against a COOH-terminal
      sequence shared by alpha-subunits of the inhibitory G proteins G(i)1 and G(i)2,
      and by an anti-PLC-gamma 1 antibody, whereas anti-G(i) alpha 3, anti-Gq/11 alpha,
      and anti-PLC-beta 1 antibodies had no effect. In contrast, pertussis toxin or the
      anti-G(i) alpha 1-2 antibody had no effect on EGF-induced tyrosine
      phosphorylation of PLC-gamma 1. EGF promoted association of G(i) proteins with
      both the EGF receptor and PLC-gamma 1 with similar kinetics as EGF-receptor
      autophosphorylation. All EGF-induced responses were abolished by the specific
      tyrosine kinase inhibitor pp60v-arc (137-157), suggesting that EGF-receptor
      tyrosine kinase activity is essential for G(i)1-2-mediated activation of PLC
      gamma 1. However, there was no evidence of tyrosine phosphorylation of G(i) alpha
      1-2. Taken together, these data show that EGF causes activation of PLC-gamma 1 by
      a mechanism requiring activation of G(i)1-2 and only a small increase in tyrosine
      phosphorylation of PLC-gamma 1.

PMID- 9176241
TI  - A new role for an old molecule: serotonin as a mitogen.
AB  - Serotonin (5-hydroxytryptamine) has been known for the last half century to
      influence vasoactivity and to participate in neurotransmission. More recently,
      this compound has been recognized to cause proliferation of a variety of cells in
      culture, including those of vascular smooth muscle. Furthermore, the
      proliferative effect is synergistic with that of more conventional growth
      producing polypeptides. A hypertrophic, as well as a proliferative response, has
      been shown to occur in some smooth muscle cells. Whether the mitogenic effect is
      initiated through a cell surface receptor or a serotonin transporter, or both
      depending on the cell type, is currently unresolved. Most evidence indicates that
      cellular cyclic nucleotides play an important role in the intracellular signaling
      process for growth regulation by serotonin, and newer studies point to protein
      phosphorylation pathways as being important in the mitogenic response. It has
      been proposed that, through these signaling pathways, serotonin plays an
      important role in remodeling of both the pulmonary and systemic circulations.

PMID- 9176242
TI  - Endothelin-1 mediates nitro-L-arginine vasoconstriction of hypertensive rat
      lungs.
AB  - Inhibition of endothelium-derived nitric oxide (NO) synthesis by L-arginine
      analogs such as nitro-L-arginine (L-NNA) elicits marked precapillary
      vasoconstriction in lungs from rats with chronic hypoxia-induced pulmonary
      hypertension. To investigate the role of endogenous endothelin (ET)-1 in L-NNA
      induced vasoconstriction, we tested, in salt solution-perfused hypertensive lungs
      isolated from chronically hypoxic (3-4 wk at barometric pressure = 410 mmHg)
      adult male rats, if the pressor responses to L-NNA and exogenous ET-1 were
      inhibited by either separate or combined ETA and ETB receptor blockade. Whereas
      only combined pretreatment with 5 microM BQ-123 (selective ETA receptor blocker)
      and 5 microM BQ-788 (selective ETB receptor blocker) inhibited the response to
      100 microM L-NNA, the response to 10 nM ET-1 was reduced by both BQ-123 alone and
      the combined blockers. Because exogenous ET-1 causes postcapillary
      vasoconstriction in salt solution-but not blood-perfused normotensive rat lungs,
      we next compared effects of ETA and ETB receptor blockade on L-NNA and ET-1
      vasoconstrictions in blood-perfused hypertensive lungs. In this case, the
      combined but not the separate effects of BQ-123 and BQ-788 inhibited the
      responses to both L-NNA and ET-1. The last experiment showed that the use of BQ
      788 to inhibit ETB receptor-mediated clearance of circulating ET-1 resulted in
      greater accumulation of endogenous ET-1 in the perfusate of hypertensive than of
      normotensive lungs. There was no difference between L-NNA-treated and vehicle
      control hypertensive lungs in accumulation of ET-1. These results suggest that
      increased endogenous levels of ET-1 acting through stimulation of both ETA and
      ETB receptors contribute to the vasoconstriction unmasked by inhibition of NO
      synthesis in hypertensive rat lungs. The increased ET-1 is apparently not due to
      the inhibition of NO synthesis, but, instead, its underlying stimulation of
      smooth muscle cell contraction is counteracted by NO activity.

PMID- 9176243
TI  - Localization and activation of type IV collagenase/gelatinase at endothelial
      focal contacts.
AB  - The cell-surface localization and site of activation of type IV
      collagenases/gelatinases (matrix metalloproteinases, MMP) in bovine pulmonary
      microvascular endothelial (BPMVE) cells was examined. Sucrose density
      centrifugation of plasma membranes and immunofluorescent staining of whole cells
      indicated association of 72 kDa (MMP-2) and 96 kDa (MMP-9) type IV
      collagenase/gelatinases with the plasma membrane. Incubation of the BPMVE cells
      with rhodaminated MMP-9 demonstrated colocalization with beta 1-integrin,
      indicating incorporation into the focal contacts. The focal contacts were
      extracted with saponin, and associated proteolytic activity was examined by
      zymography. The focal contacts contained latent MMP-2, and stimulation of the
      cells with cytochalasin D or with 8-bromoadenosine 3',5'-cyclic monophosphate
      with 3-isobutyl-1-methylxanthine increased both latent and activated MMP-9 in the
      focal contacts. Addition of these stimuli in unconditioned culture medium did not
      produce this effect, indicating that the MMP-9 in focal contact extracts was
      derived from previously secreted enzyme. The activated metalloproteinase degraded
      extracellular matrix collagens and was inhibited by 1,10-phenanthroline. These
      findings indicate that endothelial cells release MMP into the extracellular
      milieu and then concentrate and activate MMP-9 from medium at the focal contacts.

PMID- 9176244
TI  - Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung
      tissue.
AB  - We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an
      arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on human
      pulmonary arterial tone. 20-HETE elicited a dose-dependent and indomethacin
      inhibitable vasodilation of isolated small pulmonary arteries. Whole lung
      microsomes metabolized [24C]arachidonic acid into 20-HETE and a variety of
      leukotrienes, epoxyeicosatrienoic acids, and prostanoids. Indomethacin blocked
      formation of prostanoids without effects on the conversion of arachidonate into
      20-HETE, 20-HETE was converted by lung microsomes into prostanoids, raising the
      possibility that 20-HETE may be metabolized by cyclooxygenase enzymes in vascular
      tissue to a vasodilatory compound. Western blots probed with a polyclonal
      antibody to cP450 4A identified a protein of approximately 50 kDa immunologically
      similar to the cP450 4A in rat liver. We conclude that small arteries from human
      lungs dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and
      that the proteins and enzymatic activity required to synthesize this product are
      present in lungs. Our observations suggest that cP450 enzyme products could be
      endogenous modulators of pulmonary vascular tone.

PMID- 9176245
TI  - Type II pneumocytes release chemoattractant activity for monocytes
      constitutively.
AB  - In the present investigation, we determined whether A549 cells, a type II
      pneumocyte cell line, might release mediators that are responsible for monocyte
      chemoattractant activity (MCA) constitutively. To test this hypothesis, A549 cell
      supernatant fluids were harvested and evaluated for monocyte chemotaxis. A549
      cell supernatant fluids showed MCA in a time-dependent manner (P < 0.001).
      Checkerboard analysis of 24- and 72-h supernatant fluids showed that the activity
      was chemokinetic rather than chemotactic. Partial characterization of 24- and 72
      h supernatant fluids revealed that the mediator was composed of lipid-soluble
      activity that was blocked by lipoxygenase inhibitors and trypsin-sensitive
      activity blocked by cycloheximide. Molecular sieve column chromatography
      identified four molecular weight peaks. Two of four peaks were blocked by anti
      monocyte chemoattractant protein-1 (MCP-1) and anti-transforming growth factor
      beta (TGF-beta) polyclonal antibodies. MCP-1 and TGF-beta were detected by enzyme
      linked immunosorbent assay. Leukotriene B4 (LTB4) receptor antagonist attenuated
      the lowest-molecular-weight peak chemotactic response, and the concentration of
      LTB4 was high enough for chemotactic activity. These findings suggest that type
      II pneumocytes may modulate the recruitment of monocytes into the alveolar space
      by releasing MCP-1, TGF-beta, and LTB4 constitutively.

PMID- 9176246
TI  - Glucocorticoid receptor signaling in a bronchial epithelial cell line.
AB  - Glucocorticoids are an effective anti-inflammatory therapy for the treatment of
      asthma. The anti-inflammatory effects of glucocorticoids may be due to the
      inhibition of transcription factors that regulate cytokine synthesis. Because of
      the potential role of the bronchial epithelium in asthmatic inflammation and the
      possibility that this cell may be the main target of inhaled glucocorticoids, we
      have characterized glucocorticoid receptors (GR) and GR signaling in the human
      bronchial epithelial cell line BEAS-2B. Western blot analysis and radioligand
      binding studies demonstrated that BEAS-2B cells have functional GR that bind to
      dexamethasone (Dex) (dissociation constant = 5.6 nM and maximal density of
      binding sites = 228 +/- 3.3 fmol/mg protein). GR were activated by Dex as
      assessed using a glucocorticoid-responsive reporter plasmid. Transfection of BEAS
      2B cells with an activator protein-1 (AP-1) reporter construct followed by 12-O
      tetradecanoylphorbol-13-acetate (TPA) treatment resulted in a fivefold induction
      of reporter gene activity. Transfection with a nuclear factor (NF)-kappa B
      reporter construct followed by tumor necrosis factor-alpha (TNF-alpha) treatment
      resulted in a 10-fold induction of reporter gene activity. Dex (10(-7) M)
      markedly repressed both the induced AP-1 and NF-kappa B activity. The GR
      antagonist RU-486 inhibited the repressive effect of Dex on TNF-alpha-induced NF
      kappa B activity by 81% but only counteracted the repressive effect of Dex on TPA
      induced AP-1 activity by 43%. These studies demonstrate that cross-signaling
      between AP-1 and NF-kappa B with GR may explain the anti-inflammatory properties
      of glucocorticoids in airway epithelial cells.

PMID- 9176247
TI  - Sex hormones regulate CFTR in developing fetal rat lung epithelial cells.
AB  - Sex hormones modulate two normal processes of late-gestation mammalian lung
      development: the onset of augmented production of surfactant phospholipids and
      the loss of mesenchymal cells. As prenatal lung development advances, epithelial
      chloride secretory pathways diminish as opposing sodium absorptive pathways
      increase in expression. We hypothesized that sex hormones may influence both the
      gene expression and functional activity of the chloride channel known as the
      cystic fibrosis transmembrane conductance regulator (CFTR) in fetal lung
      epithelium. We report here that sex hormones exert opposite effects on CFTR.
      Androgen increases and estrogen decreases CFTR functional activity [as assessed
      by CFTR antisense (but not sense) oligodeoxynucleotide-sensitive adenosine 3',5'
      cyclic monophosphate-stimulated cell volume reduction or by glibenclamide
      sensitive, amiloride-insensitive transepithelial electrical potential] in primary
      cultures of fetal rat lung epithelial cells. No alterations in CFTR mRNA levels
      measured by quantitative polymerase chain reaction amplification of reverse
      transcripts) accompanied either the changes in functional activity induced by sex
      hormones or the changes observed during normal development, suggesting that sex
      hormone modulation of CFTR in antenatal lung occurs at a posttranscriptional
      level. Our data are consistent with the hypothesis that both androgen and
      estrogen contribute to the male disadvantage with respect to fetal lung
      functional development.

PMID- 9176248
TI  - Activation of alveolar macrophages and lung host defenses using transfer of the
      interferon-gamma gene.
AB  - Interferon-gamma (IFN-gamma) is a critical cytokine in pulmonary host defenses
      against both intracellular and extracellular pathogens. To investigate whether
      this cytokine could be used therapeutically, we constructed an E1-deleted
      recombinant adenovirus encoding murine IFN-gamma. After intratracheal inoculation
      in rats, this vector resulted in prolonged expression of functional cytokine in
      vivo, as demonstrated by increased alveolar macrophage class II major
      histocompatibility complex expression, enhanced release of tumor necrosis factor
      in response to lipopolysaccharide, and enhanced host defenses against Pseudomonas
      aeruginosa. We postulate that this vector may be useful to study the role of
      exogenous IFN-gamma in a variety of pulmonary intracellular and extracellular
      pathogens.

PMID- 9176249
TI  - Glucocorticoids increase fatty-acid synthase mRNA stability in fetal rat lung.
AB  - Fatty-acid synthase (FAS) is a critical enzyme in surfactant biosynthesis. In
      fetal lung, glucocorticoids increase synthesis of phosphatidylcholine, the
      principal lipid component of surfactant, and there is evidence that this effect
      is mediated by increased expression of the FAS gene. Dexamethasone increases FAS
      activity, mass, mRNA content, and rate of transcription in cultured explants of
      fetal rat lung. As previous experiments with actinomycin D suggested that
      dexamethasone may also increase FAS mRNA content by a posttranscriptional
      mechanism, we examined the effect of the hormone on FAS mRNA stability. Explants
      of 19-day fetal rat lungs were cultured for 44 h with and without 100 nM
      dexamethasone. Some explants were harvested at that point, and others were
      cultured further with 60 microM 5,6-dichlororibofuranosylbenzimidazole (DRB), an
      inhibitor of transcription. RNA was then extracted, and FAS mRNA levels were
      measured by Northern analysis, mRNA stability was assessed by comparing the
      amount remaining after culture with DRB with the initial level before addition of
      the inhibitor. The apparent half-life of FAS mRNA was 4 h in control explants
      cultured without hormone. FAS mRNA stability was increased 84% in the explants
      cultured with dexamethasone for 44 h and by 40% in those cultured with the
      hormone for 5 h. We conclude that glucocorticoids enhance expression of the FAS
      gene in fetal lung by increasing mRNA stability in addition to stimulating
      transcription.

PMID- 9176250
TI  - Effects of cAMP on serotonin evoked calcium transients in cultured rat airway
      smooth muscle cells.
AB  - Agents increasing intracellular adenosine 3',5'-cyclic monophosphate (cAMP) cause
      relaxation of airway smooth muscle. However, the mechanisms of their action are
      not fully understood. We investigated the role of cAMP in the modulation of
      intracellular Ca2+ concentration ([Ca2+]i) transients evoked by serotonin (5-HT)
      in cultured rat tracheal smooth muscle (TSM) cells. Forskolin (10(-7) M) caused a
      significant elevation of intracellular cAMP and a 60% relaxation of tracheal
      rings contracted with 5-HT but did not affect [Ca2+]i in TSM cells. Forskolin
      (10(-5) M) completely relaxed tracheal rings and significantly decreased [Ca2+]i
      during the sustained phase of the 5-HT response. Forskolin-induced relaxation was
      attenuated by the cAMP-dependent protein kinase A (PKA) inhibitor Rp diastereomer
      of cAMP (Rp-cAMPS; 10(-4) M) and by the guanosine 3',5'-cyclic monophosphate
      (cGMP)-dependent protein kinase (PKG) inhibitor [Rp isomer of 8-(4
      chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, 10(-4) M]. The
      effects of forskolin on [Ca2+]i were not altered by the PKA inhibitor but were
      abolished by the PKG inhibitor and thapsigargin. These results indicate that, in
      rat TSM, the relaxant effects of high concentrations of cAMP may be mediated, at
      least in part, by facilitating the sequestration of Ca2+ into intracellular
      stores by a mechanism involving PKG.

PMID- 9176251
TI  - Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and
      in vitro.
AB  - Within the alveolar space pulmonary surfactant is converted from the surface
      active large aggregates (LA) to the inactive small aggregates (SA). This
      conversion is affected by a change in surface area, lung injury, breathing
      pattern, and protease activity. This study examined the effect of N-nitroso-N
      methylurethane-induced acute lung injury on aggregate conversion in mechanically
      ventilated and spontaneously breathing rabbits. Both the in vitro surface area
      cycling techniques and the in vivo technique of intratracheally injecting
      radiolabeled LA were used for analyzing aggregate conversion. Mechanical
      ventilation of injured lungs resulted in increased aggregate conversion and
      increased surfactant aggregate ratios compared with controls. Spontaneously
      breathing injured animals had aggregate conversion and aggregate ratios that were
      not significantly different from controls. In vitro aggregate conversion was
      slower for LA obtained from injured animals compared with normal animals. We
      conclude that the mechanical stress of mechanical ventilation results in
      increased aggregate conversion and aggregate ratios. Furthermore, in vitro
      conversion of isolated LA does not necessarily reflect the conversion of
      aggregates within the alveoli.

PMID- 9176252
TI  - Ozone inactivates cyclooxygenase in human tracheal epithelial cells without
      altering PGHS-2 mRNA or protein.
AB  - Exposure of human tracheal epithelial (TE) cells to ozone (0.1-0.5 ppm) leads to
      a transient increase followed by decreased production of prostaglandin (PG) E2
      concomitant with dose-dependent loss and delayed recovery of cyclooxygenase (CO)
      activity [S.E. Alpert and R.W. Walenga. Am. J. Physiol. 269 (Lung Cell. Mol.
      Physiol. 13): L734-L743, 1995]. Formation of reactive oxygen species (ROS) in
      cultured tracheobronchial epithelial cells during ozone exposure was recently
      demonstrated (L.C. Chen and Q.Qu. Toxicol. Appl. Pharmacol. 143: 96-101, 1997).
      In the present study, we investigated if ROS generated by ozone-exposed human TE
      cells contribute to PGE2 production and/or CO inactivation and whether the delay
      in recovery of CO activity after ozone reflects impaired gene transcription
      and/or protein synthesis. Rapid, dose-dependent ROS generation, assessed by
      fluorescence of dihydrorhodamine 123, was detected in human TE monolayers exposed
      to 0.21-0.63 ppm ozone. In a different system, TE cells were exposed to air or
      0.5 ppm ozone for 1 h by serial renewal/collection of an adherent film of media.
      Ozone-induced ROS formation, the transient increase and decline in PGE2, and CO
      inactivation were attenuated by an intracellular hydroxyl radical scavenger, 1,3
      dimethyl-2-thiourea. Ibuprofen, a reversible CO inhibitor, prevented PGE2 release
      during ozone exposure (and hence autocatalytic CO inactivation) but not loss of
      CO activity. Although CO activity remained depressed for hours after ozone
      exposure, compared with air-exposed cultures, no differences were detected in
      mRNA and protein levels of prostaglandin endoperoxide G/H synthase 2 (PGHS-2),
      the only CO isoform present in human TE cells, or in the rate of de novo PGHS-2
      synthesis. Our findings suggest that ozone-induced PGE2 production and CO
      inactivation are primarily the result of formation of intracellular oxidant
      molecules and that delayed recovery of CO activity in human TE cells after short
      term ozone exposure is due to persistent inactivation of PGHS-2, rather than to
      interference with its synthesis.

PMID- 9176253
TI  - Effect of defensins on interleukin-8 synthesis in airway epithelial cells.
AB  - Neutrophils play an important role in inflammatory processes in the lung and may
      cause tissue injury through, for example, release of proteinases such as
      neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils
      also release small nonenzymatic and cationic polypeptides termed defensins. The
      aim of the present study was to investigate whether defensins induce interleukin
      (IL)-8 expression in cells of the A549 lung epithelial cell line and in human
      primary bronchial epithelial cells (PBEC). Supernatants of defensin-treated A549
      cells contained increased neutrophil chemotactic activity (16-fold) that was
      inhibited by antibodies against IL-8. Concurrently, within 3 and 6 h, defensins
      significantly increased the IL-8 levels in supernatants of both A549 cells (n =
      6, P < 0.05 and P < 0.01, respectively) and PBEC (n = 4, P < 0.001 and P < 0.001,
      respectively). This defensin-induced increase was fully inhibited by the serine
      proteinase inhibitor alpha 1-proteinase inhibitor. In addition, defensins also
      increased IL-8 mRNA levels (12-fold); this increase was dependent on de novo mRNA
      synthesis and did not require protein synthesis. Furthermore, defensins did not
      affect IL-8 mRNA stability, indicating that the enhanced IL-8 expression was due
      to increased transcription. Our findings suggest that defensins, released by
      stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and
      thus may mediate the recruitment of additional neutrophils into the airways.

PMID- 9176254
TI  - Intracellular generation of reactive oxygen species in endothelial cells exposed
      to anoxia-reoxygenation.
AB  - Reactive oxygen species (ROS) play an important role in the pathogenesis of
      ischemia-reperfusion injury. Extracellular H2O2 generation from bovine pulmonary
      artery endothelial cells (EC) is known to increase in response to anoxia
      reoxygenation (A-R). To determine potential sources of intracellular ROS
      formation in EC in response to A-R, a fluorometric assay based on the oxidation
      of 2',7'-dichlorofluorescin was used. Intracellular ROS production declined 40%
      during 6 h of anoxia (P < 0.05). After A-R, the rates of intracellular ROS
      formation increased to 148 +/- 9% (P < 0.001) that of normoxic EC (100 +/- 3%).
      In EC exposed to A-R, allopurinol and NG-methyl-L-arginine (L-NMMA), inhibitors
      of xanthine oxidase (XO) and nitric oxide synthase (NOS), respectively, reduced
      intracellular ROS formation by 25 +/- 1% (P < 0.001) and 36 +/- 4% (P < 0.01).
      Furthermore, at low doses (i.e., 20 microM), deferoxamine and
      diethylenetriaminepentaacetic acid (DTPA) significantly inhibited intracellular
      ROS formation. However, at 100 microM, only deferoxamine caused further reduction
      in DCF fluorescence. In summary, EC respond to A-R by generating increased
      amounts of XO- and NOS-derived intracellular ROS. The inhibition, to a similar
      extent, caused by allopurinol and L-NMMA, as well as the effect of deferoxamine
      and DTPA suggest that the ROS detected is peroxynitrite. Based on these findings
      and previous work, we conclude that EC generate ROS in response to A-R from at
      least two different sources: a plasma membrane-bound NADPH oxidase-like enzyme
      that releases H2O2 extracellularly and XO, which generates intracellular O2-,
      which in turn may react with nitric oxide to form peroxynitrite.

PMID- 9176256
TI  - Assembly of exogenous fibronectin into type II cell extracellular matrix.
AB  - Type II pulmonary epithelial cells (T2P) in primary culture assemble a
      biologically active extracellular matrix (ECM) from endogenously synthesized
      components, including fibronectin. Fibronectin is a well-recognized attachment
      protein that mediates cell adhesion, migration, and cytodifferentiation. In some
      cell types, exogenous fibronectin also is incorporated into ECM. The latter
      pathway of ECM assembly was thus investigated in T2P. Cells were cultured for 3
      days in Dulbecco's modified Eagle's medium (DMEM) with or without 10% fetal calf
      serum (FCS), a source of exogenous fibronectin. Cell and matrix fractions were
      harvested on culture days 1, 2, and 3 to determine synthesis of cell and matrix
      proteins and matrix fibronectin content. During 3 days in DMEM containing 10%
      FCS, T2P flattened and spread to confluence more rapidly than cells in DMEM; they
      also produced ECM with higher fibronectin content than did cells in DMEM alone.
      On culture days 2 and 3, 10% FCS doubled (on average) synthesis of ECM
      fibronectin; in contrast, ECM fibronectin content increased nearly 10-fold. These
      observations suggest that cultured type II cells incorporate exogenous
      fibronectin into newly assembled ECM to a greater extent than the newly
      synthesized glycoprotein. Components of both endogenous and exogenous origin may
      therefore contribute to T2P assembly of a biologically active ECM.

PMID- 9176255
TI  - Recombinant human superoxide dismutase reduces lung injury caused by inhaled
      nitric oxide and hyperoxia.
AB  - We previously demonstrated that 48 h of 100 ppm inhaled nitric oxide (NO) and 90%
      O2 causes surfactant dysfunction and pulmonary inflammation in mechanically
      ventilated newborn piglets. Because peroxynitrite (the product of NO and
      superoxide) is thought to play a major role in the injury process, recombinant
      human superoxide dismutase (rhSOD, a scavenger of superoxide) might minimize this
      insult. Four groups of newborn piglets (1-3 days of age) were ventilated with 100
      ppm NO and 90% O2 for 48 h. Piglets received no drug, 5 mg/kg rhSOD
      intratracheally at time 0, 5 mg/kg rhSOD intratracheally at 0 and 24 h, or 10
      mg/kg rhSOD by nebulization at time 0. At 48 h, bronchoalveolar lavage (BAL) was
      performed, and lung tissue was analyzed for markers of inflammation, oxidative
      injury, acute lung injury, and surfactant function. There were significant
      differences between rhSOD-treated piglets and untreated controls with respect to
      BAL neutrophil chemotactic activity, cell counts, and protein concentration as
      well as lung tissue malondialdehyde concentrations. Minimum surface tension of
      BAL surfactant from all groups studied was increased, with no differences found
      among groups. These data suggest that rhSOD, at the doses used, mitigated the
      inflammatory changes, oxidative damage, and acute lung injury from exposure to
      100 ppm NO and 90% O2 but did not appear to improve surfactant function. This has
      important clinical implications for infants treated with hyperoxia and NO for
      neonatal lung disorders.

PMID- 9176257
TI  - Chronic effects of catecholamines on the beta 2-adrenoreceptor system in cultured
      human airway epithelial cells.
AB  - Chronic catecholamine treatment induces beta-adrenergic receptor (beta AR)
      downregulation, i.e., a loss of total cell receptors. In the human respiratory
      tract, the mechanism(s) underlying beta AR downregulation remains poorly
      understood. The present study, therefore, examined the effects of 24 h of
      exposure to isoproterenol (Iso; 10 nM or 1 microM) on beta AR density and the
      rate of beta AR degradation, steady-state beta 2-adrenergic receptor (beta 2 AR)
      mRNA levels, and the content of Gs alpha and Gi alpha proteins in cultured human
      bronchial epithelial cells (i.e., the BEAS-2B cell line). beta AR density
      assessed by binding with [125I]iodopindolol decreased in a dose-dependent fashion
      with 24 h of Iso exposure. With Iso (1 microM), beta AR density decreased by
      approximately 82%. In contrast, forskolin (100 microM) and dibutyryl adenosine
      3',5'-cyclic monophosphate (1 mM), agents that also increase adenosine 3',5'
      cyclic monophosphate (cAMP) levels, had no significant effect on beta AR density.
      Iso exposure also elicited a concomitant decrease in Iso-stimulated cAMP but had
      no significant effect on the content of the G proteins G alpha i2 and Gs alpha
      assessed by immunoblotting and toxin-catalyzed ADP ribosylation. Of note, Iso
      exposure (1 microM) had no effect on steady-state levels of beta 2 AR mRNA
      measured both by Northern analysis and by reverse transcriptase-polymerase chain
      reaction. However, beta AR half-life assessed in the presence of the protein
      synthesis inhibitor cycloheximide was reduced by approximately 60% in Iso-treated
      cells (i.e., from 37 h in control to 16 h in 1 microM Iso). These results suggest
      that, in human airway epithelial cells, beta 2 AR downregulation 1) is not
      primarily driven by intracellular cAMP levels, 2) is not associated with
      significant decreases in steady-state levels of beta 2 AR mRNA, and 3) is largely
      posttranslationally regulated by increases in the rate of receptor protein
      degradation.

PMID- 9176258
TI  - Bronchoalveolar macrophage CD14 expression: shift between membrane-associated and
      soluble pools.
AB  - The bacterial endotoxin [lipopolysaccharide (LPS)]-binding protein CD14 modulates
      the host response to LPS, but membrane-associated and soluble forms of the
      molecule exert different biological effects. CD14 anchored to the mononuclear
      phagocyte membrane (mCD14) enhances response to LPS. Soluble CD14 (sCD14) may
      block LPS stimulation of CD14-bearing cells while supporting LPS presentation to
      non-CD14-bearing cells. We analyzed cell mCD14 and sCD14 expression in
      simultaneously collected human bronchoalveolar macrophages (BAM) and peripheral
      blood monocytes (PBM). Expression of mCD14 in freshly isolated BAM was only 9% as
      high as in PBM. Levels of sCD14 in 48 h in BAM culture supernatants were 19% as
      high as in PBM cultures. Interleukin (IL)-6 increased CD14 expression in both BAM
      and PBM but exerted different effects on CD14 distribution in these cell types.
      IL-6 increased only sCD14 release (2.5-fold) in BAM while increasing only mCD14
      expression (2.5-fold) in PBM. IL-4 reduced both mCD14 (> 40%) and sCD14 (> 60%)
      expression in both cell types. We speculate that the balance between sCD14 and
      mCD14 expression influences the response to aspirated or inhaled LPS in the
      bronchoalveolar compartment. Cytokine expression and monocyte recruitment may
      influence this process by modulating CD14 expression.

PMID- 9176259
TI  - Hypoxia inhibits the induction of argininosuccinate synthetase by endotoxin in
      lung endothelial cells.
AB  - Pulmonary artery endothelial cells (PAEC) possess a two-step pathway for
      synthesizing L-arginine from L-citrulline. The first and rate-limiting step is
      catalyzed by argininosuccinate synthetase (AS). We have previously shown that
      hypoxia inhibits synthesis of L-arginine from L-citrulline in PAEC. In this
      study, we examined the effect of hypoxia on the induction of AS in PAEC. Porcine
      PAEC were incubated with or without endotoxin under normoxia (air-5% CO2) or
      hypoxia (0% O2-95% N2-5% CO2) for 24 h, and then AS activity and AS mRNA content
      were determined. Incubation with endotoxin resulted in increases in AS activity
      and mRNA, and the latter was blocked by actinomycin D. Exposure to hypoxia for 24
      h decreased AS activity and mRNA content and stability, and it also abolished the
      increases in AS activity and mRNA induced by endotoxin. These results indicate
      that hypoxia inhibits endotoxin-mediated induction of AS. This inhibition might
      reduce the availability of intracellular L-arginine and thereby limit
      immunostimulant-induced nitric oxide production by lung endothelial cells.

PMID- 9176260
TI  - Purification and immunohistochemical localization of the ATP diphosphohydrolase
      in bovine lungs.
AB  - We have recently described different isoforms of mammalian ATP diphosphohydrolase
      (ATPDase; EC 3.6.1.5). In the present study, we purified the lung ATPDase by
      column chromatographies followed by polyacrylamide gel electrophoresis under
      nondenaturing conditions. The active polypeptide that has a molecular mass of 78
      kDa was identified by affinity labeling to the ATP analog 5'-p
      fluorosulfonylbenzoyladenosine (FSBA), followed by detection on Western blot with
      an antibody specific for FSBA. N-glycosidase F treatment shifted the molecular
      mass of the 78-kDa polypeptide down to 54 kDa, indicating that the enzyme bears
      approximately 6-12 NH2-linked oligosaccharide chains. A polyclonal antibody
      raised against the pancreas ATPDase, which specifically recognized the 78-kDa
      glycoprotein on Western blot, was used to carry out an immunological survey of
      the enzyme distribution in bovine lungs. Immunoreactivity was detected on airway
      epithelia from the trachea down to alveolar cells, airway and vascular smooth
      muscle cells, submucous glands, chondrocytes, leucocytes, as well as endothelial
      and mesothelial cells. Such a wide distribution suggests that the ATPDase may
      affect a variety of physiological effects mediated by extracellular nucleotides,
      such as airway smooth muscle tone, surfactant secretion, platelet aggregation,
      and inflammation.

PMID- 9176261
TI  - Vectorial transcytosis of dimeric IgA by the Calu-3 human lung epithelial cell
      line: upregulation by IFN-gamma.
AB  - We have developed an in vitro airway epithelial cell model for dimeric
      immunoglobulin (Ig) A (dIgA) transcytosis that allows the assessment of polymeric
      Ig receptor (pIgR) gene expression and actual dIgA transport. Tight monolayers of
      human lung-derived Calu-3 adenocarcinoma cells grown on permeable membranes
      expressed pIgR mRNA and released more secretory component (SC; P < 0.01) and
      secretory IgA (sIgA; P < 0.02) into the apical medium than into the basolateral
      medium. Transcytosis of dIgA was not due to paracellular leakage and was
      inhibited to approximately 20 and 30% of control values by anti-pIgR antibodies
      and the competitive ligand pentameric IgM, respectively. Interferon-gamma (IFN
      gamma; 200 U/ml) induced pIgR mRNA expression and increased apical release of
      free SC and sIgA in a dose-dependent fashion (P < 0.0001). Basolateral addition
      of increasing amounts of dIgA dose dependently increased apical sIgA release (P <
      0.0001). These data indicate that Calu-3 monolayers are capable of translocating
      dIgA through the pIgR. In addition, we show the integrated stimulatory effect of
      IFN-gamma on pIgR mRNA and protein expression and dIgA transcytosis.

PMID- 9176262
TI  - Role of calcium-activated chloride current in regulating pulmonary vasomotor
      tone.
AB  - Many agonists induce vasoconstriction by releasing intracellularly stored Ca2+
      and promoting Ca2+ influx. Activation of Ca(2+)-activated Cl- (ClCa) channels may
      be a critical mechanism by which a rise in intracellular free Ca2+ concentration
      ([Ca2+]i) causes membrane depolarization that serves to sustain the elevated
      [Ca2+]i and maintain vascular tone. In this study the biophysical and
      pharmacological properties of ClCa currents [ICKCa] were characterized in rat
      pulmonary artery (PA) smooth muscle cells, and their relationship to the
      regulation of pulmonary vascular tone was determined. When K+ currents were
      eliminated by using Cs(+)-containing internal solution, depolarization elicited
      an inward Ca2+ current followed by a time-dependent outward Cl- current that
      reversed near Cl- equilibrium potential. Repolarizing voltage steps produced a
      large inward tail Cl- current that also reversed at a potential close to Cl-
      equilibrium potential. Replacement of extracellular Ca2+ with Ba2+ significantly
      augmented the Ca2+ current but abolished the Cl- currents. The Cl- channel
      blocker niflumic acid (10-50 microM) diminished the time-dependent outward Cl-
      current and the inward tail Cl- current, decreased serotonin-induced membrane
      depolarization, and inhibited agonist-induced PA contraction. In the absence of
      extracellular Ca2+, cyclopiazonic acid, which releases Ca2+ from sarcoplasmic
      reticulum, elicited an inward Cl- current at a holding potential of -70 mV. These
      results indicate that rat PA myocytes possess ClCa channels that are activated by
      depolarization-induced Ca2+ influx and agonist-induced Ca2+ release. This Cl-
      current contributes to agonist-induced pulmonary vasoconstriction via membrane
      depolarization.

PMID- 9176263
TI  - Persistent eNOS in lung hypoplasia caused by left pulmonary artery ligation in
      the ovine fetus.
AB  - Because increased flow and shear stress upregulate endothelial (e) nitric oxide
      synthase (NOS) in adult endothelial cells in vivo and in vitro, we hypothesized
      that decreased pulmonary blood flow would decrease eNOS content in the late
      gestation ovine fetus. To investigate the effects of decreased blood flow and the
      potential role of altered eNOS content in lung hypoplasia, we studied an animal
      model of lung hypoplasia after left pulmonary artery (LPA) ligation in nine fetal
      lambs (114-124 days gestation; term = 147 days). After at least 14 days, animals
      were killed, and lungs were harvested for histology, immunostaining, Western blot
      analysis for eNOS protein content, and biochemical assays of NOS activity. LPA
      ligation markedly reduced left lung size. Histology demonstrated loose connective
      tissue and airway immaturity in the left lungs. eNOS immunostaining demonstrated
      equal staining in the left pulmonary vessels compared with the right. Solitary
      endothelial cells staining for eNOS and factor VIII-related antigen were observed
      throughout the mesenchyme of left, but not right, lungs. eNOS protein content and
      activity were similar in left and right lungs. We conclude that, despite the
      absence of pulmonary blood flow and marked lung hypoplasia, eNOS content and NOS
      activity were not reduced after LPA ligation in the late fetal lung. We speculate
      that low pulmonary blood flow does not downregulate fetal pulmonary vascular eNOS
      expression and that other factors, such as paracrine or autocrine stimuli, may
      account for the persistence of eNOS in the developing lung circulation.

PMID- 9176264
TI  - Endothelial barrier dysfunction and p42 oxidation induced by TNF-alpha are
      mediated by nitric oxide.
AB  - We tested the hypothesis that nitric oxide (.NO) mediates tumor necrosis factor
      alpha (TNF-alpha)-induced alterations in permeability and actin of pulmonary
      artery endothelial monolayers (PAEM). The permeability of PAEM was assessed by
      the clearance rate of albumin labeled with Evans blue dye. The PAEM Triton
      soluble ("cytoskeletal-nonassociated") and -insoluble ("cytoskeletal-associated")
      lysates were analyzed by Western blot for actin and oxidized protein using
      polyclonal antibodies to the COOH terminus of actin and dinitrophenylhydrazone
      (DNP), respectively. PAEM were incubated with TNF-alpha (100 U/ml) for 4 h.
      Incubation of PAEM with TNF-alpha resulted in increases in 1) the .NO oxidation
      product nitrite (NO2-), 2) nitrotyrosine immunofluorescence, 3) the oxidation of
      p42 (tentatively identified as actin), and 4) permeability to Evans blue dye
      albumin. The .NO synthase inhibitor aminoguanidine (100 microM) prevented the TNF
      alpha-induced increase in NO2-, nitrotyrosine immunofluorescence, oxidized p42,
      and permeability. Coincubation with L-arginine (200 microM) or the .NO mimic
      spermine-NO (1 microM) prevented the ablation of the response to TNF-alpha by
      aminoguanidine. The data indicate that TNF-alpha-induced increases in endothelial
      permeability and oxidized protein are mediated by .NO in PAEM.

PMID- 9176265
TI  - SP-A enhances uptake of bacillus Calmette-Guerin by macrophages through a
      specific SP-A receptor.
AB  - Surfactant-associated protein A (SP-A) is a C-type lectin that is involved in
      surfactant metabolism as well as host defense functions in the lung. We have
      recently identified a receptor on macrophages [specific 210-kDa SP-A receptor
      (SPR210)] that binds SP-A. In the current study we have investigated the role of
      SP-A in mediating uptake of bacillus Calmette-Guerin (BCG) by rat macrophages and
      human monocytes and have examined the role of the macrophage SPR210 in this
      process. 125I-labeled SP-A bound BCG in a Ca(2+)-, carbohydrate-, and dose
      dependent manner. To examine association of SP-A-BCG complexes with macrophages,
      BCG were opsonized with SP-A and were incubated with rat bone marrow-derived
      macrophages (RBMM), rat alveolar macrophages (RAM), or human monocytes at a 1-to
      1 ratio for 4 h. The cells were washed, fixed in formalin, and stained with
      auramine-rhodamine. Cell-associated organisms were enumerated by fluorescent
      microscopy. The percentage of cells with one or more associated BCG was increased
      by SP-A from 27% of RBMM with BCG alone to 54% with SP-A-BCG complexes; 1-16% in
      RAM; and 39-67% in human monocytes. This enhanced uptake was dependent on the
      dose of SP-A, with maximal increases seen with 10 micrograms/ml. Electron
      microscopic analysis supported the conclusion that organisms were ingested by and
      not simply bound to the macrophages. Inclusion of SPR210 antibodies blocked
      association of SP-A-BCG complexes, suggesting a role for SPR210 in mediating the
      interaction of SP-A-BCG with the macrophages. This was further supported by the
      finding that modulation of SPR210 activity resulted in altered SP-A-BCG uptake.
      These results demonstrate that SP-A binds to BCG and that uptake of these SP-A
      BCG complexes is mediated in part by the SPR210 on rat macrophages and human
      monocytes.

PMID- 9176266
TI  - Surfactant protein A regulates cytokine production in the monocytic cell line THP
      1.
AB  - Surfactant lipids inhibit cytokine production by immune cells, and surfactant
      protein A (SP-A) stimulates it. By enzyme-linked immunosorbent assay and mRNA
      blotting, we studied proinflammatory cytokine production by the monocytic cell
      line THP-1. SP-A caused increases in tumor necrosis factor (TNF)-alpha within 1
      h, peaking at 4 h and then declining. Interleukin (IL)-1 beta increased and
      stayed elevated for 24 h. SP-A stimulated IL-8 also, peaking at 4 h, rapidly
      declining, and peaking again at 24 h. SP-A-dependent changes were detected for IL
      6, but at higher SP-A doses. mRNA levels for TNF-alpha and IL-1 beta increased in
      response to SP-A, peaking within 2 h. The increases in TNF-alpha mRNA and protein
      induced by SP-A were inhibited by surfactant lipids. For IL-1 beta and IL-8, the
      lipids either had no inhibitory influence or inhibited less than for TNF-alpha.
      This suggests that the ability of macrophages to participate in inflammatory
      reactions is enhanced by SP-A alone or by mixtures of lipids and SP-A containing
      more SP-A than in normal surfactant, as occurs in many conditions leading to
      inflammation.

PMID- 9176267
TI  - Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs
      with pulmonary hypertension.
AB  - Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically
      involved in the cardiopulmonary transition from fetal to neonatal life. We have
      previously shown that NO-dependent relaxation is attenuated in intrapulmonary
      arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal
      ligation of the ductus arteriosus. In the present study, we determined whether
      this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS)
      protein expression were assessed in lungs from near-term control lambs and PHT
      lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was
      decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS
      enzymatic activity was also diminished in PHT vs. control lung (60 +/- 3 vs. 110
      +/- 7 fmol.mg protein-1.min-1, respectively). Paralleling the declines in eNOS
      protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT
      lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of
      fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle
      growth, diminished eNOS expression may contribute to both the abnormal
      vasoreactivity and the excessive muscularization of the pulmonary circulation in
      fetal PHT.

PMID- 9176268
TI  - Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide
      synthase in the ovine fetus.
AB  - Endothelial (e) nitric oxide synthase (NOS) activity modulates pulmonary vascular
      tone in the normal fetus and decreases pulmonary vascular resistance (PVR) at
      birth. Mechanisms contributing to sustained elevations of PVR and the failure of
      postnatal adaptation at birth are uncertain but may include decreased eNOS
      activity. To test this hypothesis, we studied the effects of chronic intrauterine
      pulmonary hypertension on lung eNOS content and NOS activity in an ovine model of
      perinatal pulmonary hypertension and in normal lambs. We measured eNOS mRNA and
      protein content by Northern and Western blot analyses, respectively. Calcium
      dependent and total NOS activities were determined by assaying the conversion of
      L-[14C]arginine to L-[14C]citrulline from lung homogenates. To determine the
      effects of intrauterine hypertension on lung eNOS content, fetal lung tissue was
      harvested 8-12 days after intrauterine closure of the ductus arteriosus (DA)
      performed at 125-128 days of gestation (term = 147 days). Although positive
      immunostaining for eNOS persisted in lung vascular endothelium, eNOS protein
      content was reduced by 48%, as measured by Western analysis (P < 0.001). Chronic
      hypertension reduced lung eNOS mRNA content by 30% (P < 0.05). Compared with age
      matched controls, Ca(2+)-dependent NOS activity was decreased after DA ligation
      by 75% (P < 0.01). We conclude that chronic intrauterine pulmonary hypertension
      decreases eNOS in the fetal lung. We speculate that decreased NO production
      contributes to failure of postnatal adaptation in this experimental model of
      persistent pulmonary hypertension of the newborn.

PMID- 9176269
TI  - ET-1 induces mitogenesis in ovine airway smooth muscle cells via ETA and ETB
      receptors.
AB  - The proliferation of airway smooth muscle cells is a characteristic feature of
      asthma. Endothelin (ET)-1, a member of a family of three isopeptides (ET-1, ET-2,
      and ET-3), functions as a spasmogen and mitogen for airway smooth muscle cells.
      Two types of ET receptors have been identified in mammalian species (ETA and
      ETB). Because the respective roles of ETA and ETB receptors in ET-1-induced
      mitogenesis are not known, we determined the effect of two selective ETA and ETB
      antagonists (BQ-610 and BQ-788) on ET-1-induced mitogenesis of cultured ovine
      airway smooth muscle cells. Both BQ-610 and BQ-788 inhibited ET-1-induced
      mitogenesis in a concentration-dependent manner, with BQ-788 exhibiting more
      potent antagonism [half-maximal inhibitory concentration (IC50) = 3.5 nM, slope
      of 0.49] compared with BQ-610 (IC50 = 20 nM, slope of 0.27). The combined ETA-ETB
      antagonist, bosentan, also inhibited ET-1-induced mitogenesis (IC50 = 20 nM,
      slope of 0.60). The effects of BQ-788 and bosentan appear to be mediated via the
      same receptor (ETB), as their slopes are comparable. These observations suggest
      that both receptor subtypes are utilized in ET-1-induced proliferation of ovine
      airway smooth muscle. ET receptor expression may be important in the increase in
      airway smooth muscle mass seen in the airways of patients with bronchial asthma.

PMID- 9176270
TI  - RANTES inhibits HIV-1 replication in human peripheral blood monocytes and
      alveolar macrophages.
AB  - Infection with human immunodeficiency virus (HIV)-1 most often leads to the
      development of acquired immune deficiency syndrome, which may manifest with
      opportunistic infections, many of which occur in the lung. Mononuclear phagocytes
      infected by HIV-1, being relatively resistant to its cytopathic effects,
      potentially act as a reservoir for the virus. The alveolar macrophage (AM), a
      differentiated lung tissue macrophage, is readily infected by HIV-1, after which
      the virus becomes relatively dormant. C-C chemokines, secreted by CD8 T
      lymphocytes and other cells, are known to suppress HIV replication in
      lymphocytes. In view of this observation, and the relative increase in CD8+ T
      lymphocytes during HIV-1 disease, particularly in the lung, we hypothesized that
      C-C chemokines might play a key role in suppressing HIV-1 replication in AM. We
      examined the effect of the C-C chemokines macrophage inflammatory protein (MIP)-1
      alpha, MIP-1 beta, and regulated on activation normal T cell expressed and
      secreted (RANTES) singly and in combination on HIV-1 replication in peripheral
      blood monocytes (PBM) and AM infected in vitro. Our findings indicate that RANTES
      suppresses HIV-1 replication, as measured by reverse transcriptase activity, in
      PBM (41.3 +/- 15.2% of control, n = 3, P < 0.05) and AM (30.3 +/- 7.8% of
      control, n = 3, P < 0.05) in a dose-dependent manner. The other C-C chemokines
      had no significant effect singly (MIP-1 alpha PBM: 64.8 +/- 21.9%; AM: 115.0 +/-
      2.4% of control; MIP-1 beta PBM: 68 +/- 19.6; AM: 63.3 +/- 26.2% of control) but
      modestly decreased HIV replication when incubated in addition to RANTES (24.5 +/-
      6.5% of control). These observations suggest that RANTES plays a key role in
      modulating HIV-1 replication in mononuclear phagocytes in the blood and lung, and
      this may have therapeutic implications for prevention and/or treatment of HIV
      disease.

PMID- 9176271
TI  - Temporary acidosis during reperfusion limits myocardial infarct size in dogs.
AB  - We tested the hypothesis that myocardial extracellular acidosis during early
      reperfusion limits infarct size. The left anterior descending coronary artery was
      perfused with blood through a bypass tube in dogs. We occluded the bypass tube
      for 40 (protocol I; n = 24 hearts) and 90 min (protocol II; n = 36 hearts). In
      protocols I and II, we infused one group of hearts with HCl (60 micrograms.kg
      1.min-1) for 60 min after the onset of reperfusion (the metabolic acidosis
      group), and another group of hearts were ventilated with 3 liters of 70% O2-30%
      CO2 mixed with room air 10 min before the onset of reperfusion for 70 min (the
      respiratory acidosis group). pH in the coronary venous blood and myocardial pH
      during reperfusion in the metabolic and respiratory acidosis groups were lower
      than those in the control groups. Infarct sizes in the metabolic (16.4 +/- 2.5
      and 22.3 +/- 2.5%) and respiratory (16.7 +/- 2.6 and 22.3 +/- 2.5%) acidosis
      groups in protocols I and II, respectively, were smaller than those in the
      control groups (33.1 +/- 3.0 and 40.6 +/- 4.1%, respectively). Thus we conclude
      that temporary acidosis during reperfusion limits infarct size.

PMID- 9176272
TI  - Cardiac sympathetic activity in response to acute myocardial ischemia.
AB  - Although experimental evidence has demonstrated that brief periods of myocardial
      ischemia are not associated with norepinephrine overflow from the heart, cardiac
      sympathetic responses to myocardial ischemia in humans remain unclear. Eleven
      patients undergoing angioplasty of the left anterior descending coronary artery
      had cardiac norepinephrine spillover measured immediately before inflation,
      during the final minute of a 5-min balloon inflation, and 1 min after deflation.
      Angioplasty caused significant S-T segment elevation and a reduction in the
      transcardiac lactate extraction ratio. Cardiac norepinephrine spillover was
      reduced from a mean value of 58 +/- 14 pmol/min at control to 41 +/- 15 pmol/min
      during balloon inflation and 38 +/- 14 pmol/min after deflation (P < 0.05 vs.
      control for both inflation and deflation values). In contrast, during balloon
      inflation, there were significant increases in arterial norepinephrine and
      epinephrine concentrations. Therefore, a brief period of myocardial ischemia
      caused by angioplasty of the left anterior descending coronary artery does not
      result in cardiac sympathetic activation, despite evidence of generalized
      sympathoadrenal activation.

PMID- 9176273
TI  - Chronic heat improves mechanical and metabolic response of trained rat heart on
      ischemia and reperfusion.
AB  - Cardiac mechanics and metabolic performance were studied in isolated perfused
      hearts of rats subjected to a combined chronic stress of heat acclimation and
      swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and
      systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured
      during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC),
      DP, and SP were measured during progressive graded ischemia, total ischemia (TI),
      and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured
      during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy.
      During normoperfusion, SP and cardiac efficiency (derived from rate-pressure
      product-oxygen consumption relationships) were the highest in the 2-mo EXAC
      hearts (P < 0.0001). During progressive graded ischemia, the development of IC
      (percentage of total hearts) was similar in both EXAC and EX hearts; the only
      significant difference was confined to the 1- vs. 2-mo groups. The onset of IC
      was delayed in the EXAC hearts and, on reperfusion, recovery, particularly of DP,
      was significantly improved in the latter. After TI, EXAC hearts retained 30% of
      the ATP pool and there was a delayed decline in intracellular pH. On reperfusion,
      these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo
      EXAC heart demonstrating significantly faster high-energy phosphate salvage,
      improved diastolic function, and pulse pressure recovery. The data attest to the
      beneficial effects of heat acclimation on cardiac mechanics of trained rats
      during normoperfusion and cardiac protection on ischemia and reperfusion.
      Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia
      and improved energy salvage on reperfusion contribute synergistically to this
      potent beneficial effect.

PMID- 9176274
TI  - Oxidants increase intracellular free Zn2+ concentration in rabbit ventricular
      myocytes.
AB  - Oxidative stress may alter cardiac function by affecting intracellular free Zn2+
      concentrations ([Zn2+]i). Rabbit ventricular myocytes loaded with fura 2 were
      used to fluorometrically measure resting [Zn2+]i (0.23 +/- 0.03 nM) and
      intracellular Ca2+ concentration ([Ca2+]i) (36 +/- 7 nM). Fluorescence quenching
      by the heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
      was used to quantitate [Zn2+]i. The thiol-reactive oxidants hypochlorous acid
      (0.1 mM) and selenite (1 mM) increased [Zn2+]i to 7.7 +/- 1.7 and 6.1 +/- 1.7 nM,
      respectively, within 5 min. Dithiothreitol (0.5 mM), a disulfide-reducing agent,
      rapidly restored normal [Zn2+]i. The oxidants did not affect [Ca2+]i. However,
      depolarization-induced Ca2+ transients and Ca2+ currents were zinc dependent.
      [Zn2+]i-associated fluorescence was substantial and, if ignored, it led to
      overestimation of [Ca2+]i by approximately twofold before oxidant treatment and
      by approximately eightfold after oxidants. The results demonstrate that [Zn2+]i
      1) can be greatly increased by thiol-reactive oxidants; 2) may contribute to
      oxidant-induced alterations of excitation-contraction coupling; and 3) has strong
      fura 2 fluorescence which, if overlooked, can lead to significant overestimation
      of [Ca2+]i.

PMID- 9176275
TI  - In vivo microvascular structural and functional consequences of muscle length
      changes.
AB  - As muscles are stretched, blood flow and oxygen delivery are compromised, and
      consequently muscle function is impaired. We tested the hypothesis that the
      structural microvascular sequellae associated with muscle extension in vivo would
      impair capillary red blood cell hemodynamics. We developed an intravital
      spinotrapezius preparation that facilitated direct on-line measurement and
      alteration of sarcomere length simultaneously with determination of capillary
      geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere
      lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary
      tortuosity decreased systematically with increases of sarcomere length up to 2.6
      microns, at which point most capillaries appeared to be highly oriented along the
      fiber longitudinal axis. Further increases in sarcomere length above this value
      reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns
      sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length.
      Over the range of physiological sarcomere lengths, bulk blood flow (radioactive
      microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6
      ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e.,
      those with continuous flow throughout the 60-s observation period, decreased from
      95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest
      sarcomere lengths and was correlated significantly with the reduced capillary
      diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary
      geometry and luminal diameter consequent to increased muscle sarcomere length are
      associated with a reduction in mean capillary red blood cell velocity and a
      greater proportion of capillaries in which red blood cell flow is stopped or
      intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen)
      delivery, it also alters capillary red blood cell flow dynamics, which may
      further impair blood-tissue oxygen exchange.

PMID- 9176276
TI  - Cardiac inotropic actions of urocortin in conscious sheep.
AB  - Urocortin (Ucn) is a recently isolated peptide related to the corticotropin
      releasing factor (CRF) family, which can produce hemodynamic and hormonal actions
      in conscious rats. This study examined in detail the cardiovascular actions of
      Ucn and CRF after intravenous injection in chronically instrumented, conscious
      sheep. Injection of Ucn produced dose-dependent changes in cardiac contractility
      [rate of increase of aortic flow (dF/dt)], maximum aortic flow (Fmax), mean
      arterial pressure (MAP), heart rate (HR), cardiac output (CO), and coronary blood
      flow (CF). Ucn injected at 100 micrograms produced a potent increase in dF/dt,
      from 909 +/- 44 to a maximum of 1,849 +/- 901.min-1.s-1, and in Fmax, from 25.5
      +/- 0.8 to 36.6 +/- 1.4 l/min. Cardiac contractility increased within 30 min of
      injection and remained significantly elevated for up to 24 h. MAP increased from
      78 +/- 2 to 90 +/- 3 mmHg, and HR increased from 73 +/- 4 to 103 +/- 9 beats/min.
      CO rose from 5.0 +/- 0.1 to 5.8 +/- 0.2 l/min, whereas central venous pressure,
      total peripheral conductance, and stroke volume were unchanged. All Ucn-induced
      cardiovascular effects were inhibited by prior treatment with the CRF antagonist
      alpha-helical CRF-(9-41). Equimolar doses of CRF produced little change in any
      hemodynamic parameter. Both peptides increased plasma levels of
      adrenocorticotropin and cortisol, with Ucn having a more potent effect than CRF.
      We have shown for the first time that Ucn can produce potent and long-lasting
      actions to elevate cardiac contractility in conscious animals.

PMID- 9176277
TI  - Functional implications of myocardial scar structure.
AB  - During healing after myocardial infarction, scar collagen content and stiffness
      do not correlate. We studied regional mechanics and both area fraction and
      orientation of large collagen fibers 3 wk after coronary ligation in the pig.
      During passive inflation of isolated, arrested hearts, the scar tissue
      demonstrated significantly less circumferential strain but similar longitudinal
      and radial deformation in comparison with noninfarcted regions of the same
      hearts. The observed selective resistance to circumferential deformation was
      consistent with the finding that most of the large collagen fibers in the scar
      were oriented within 30 degrees of the local circumferential axis. Furthermore,
      data from a previous study indicate that during ventricular systole these scars
      resist circumferential stretching, whereas they deform similarly to noninfarcted
      myocardium in the longitudinal and radial directions. We conclude that large
      collagen fiber structure is an important determinant of scar mechanical
      properties and that scar anisotropy allows the scar to resist circumferential
      stretching while deforming compatibly with adjacent noninfarcted myocardium in
      the longitudinal and radial directions.

PMID- 9176278
TI  - Pressure-independent effects of AT1-receptor antagonism on cardiovascular
      remodeling in aortic-banded rats.
AB  - To determine the role of angiotensin II-receptor blockade on cardiovascular
      remodeling in a pressure-overload model of cardiac hypertrophy, a
      subdiaphragmatic aortic band was placed in adult male Sprague-Dawley rats. Aortic
      banded (AB) rats were left untreated or were losartan (Los; 250 mg/l) treated (AB
      Los). Sham-operated (S) controls were either left untreated or treated with Los
      (S-Los). After 4 wk, rats were catheterized for measurement of mean arterial
      pressures [carotid (CMAP) and femoral (FMAP), in mmHg]. Hearts were perfused on a
      modified Langendorff system, and minimal coronary resistance (MCR) was
      determined. Hearts were then perfusion fixed, total and regional heart weights
      were recorded, and sections were processed for morphology. Changes in coronary
      artery medial thickness and perivascular fibrosis were assessed by quantitative
      image analysis. CMAP was significantly higher in AB and AB-Los than in S or S-Los
      (P < 0.05). There was no difference in FMAP in AB vs. S, but AB-Los and S-Los had
      lower FMAPs than S. Total heart weight and left ventricular weight-to-body weight
      ratios were increased in AB and AB-Los compared with S and S-Los (P < 0.05). MCR
      of AB was greater than S and S-Los. MCR of AB-Los was significantly lower than AB
      and was not significantly different from S and S-Los. In coronary vessels, medial
      thickness was greatest in AB, whereas there was no difference among AB-Los, S,
      and S-Los. Similarly, the increase in perivascular fibrosis was greatest in AB,
      and there was no difference among AB-Los, S, and S-Los. These data suggest that
      angiotensin II, independent of increased arterial pressure, is critical for the
      development of the vascular and fibrotic changes that occur in this model of
      pressure-overload hypertrophy.

PMID- 9176280
TI  - Sympathetic stimulation elicits increased or decreased VO2 in the perfused rat
      hindlimb via alpha 1-adrenoceptors.
AB  - The effects of lumbar sympathetic nerve stimulation on oxygen uptake (VO2) in
      curarized muscle of the perfused rat hindlimb were investigated. Stimulation of
      sympathetic nerves elicited vasoconstriction at all frequencies. Importantly,
      this was associated with changes in VO2 that were generally stimulatory at low
      frequencies (0.5-2 Hz) and inhibitory at high frequencies (5-10 Hz). Both the
      pressor response and the changes in VO2 were almost completely blocked by the
      alpha 1/alpha 2-blocker phentolamine (1.0 microM) but were not affected by the
      beta 1/beta 2-blocker DL-propranolol (2.0 microM). The alpha 2-blocker yohimbine
      (0.1 microM) did not significantly affect either the pressor or VO2 response. The
      alpha 1-antagonist prazosin (0.1 microM) abolished the vasoconstriction with low
      frequency stimulation and inhibited > 90% of the vasoconstriction with high
      frequency stimulation. Intra-arterial infusion of phenylephrine (alpha 1
      agonist), but not of UK-14304 (alpha 2-agonist), also elicited a similar biphasic
      response in VO2 during vasoconstriction. The changes in VO2 at both low- and high
      frequency stimulation were fully reversed by prazosin. The vasodilator sodium
      nitroprusside also showed similar effects to prazosin in blocking both VO2 and
      vasoconstriction. Thus sympathetic control of VO2 in the perfused rat hindlimb
      appears to be initiated by activation of predominantly vascular alpha 1
      adrenoceptors.

PMID- 9176279
TI  - Chronic effects of ANG II antagonist in heart failure: improvement of cGMP
      generation from ANP.
AB  - To evaluate the effects of endogenous angiotensin II (ANG II) on the development
      of congestive heart failure (CHF), we examined cardiorenal and hormonal factors
      after chronic administration of the ANG II type 1 receptor antagonist TCV-116 in
      dogs with CHF induced by rapid right ventricular pacing. After 8 days of pacing,
      TCV-116 administration [1 (group 1) or 3 mg.kg-1.day-1 (group 2)] was started and
      continued until the 22nd day. TCV-116 was found to have protected the
      deterioration of cardiorenal functions and the activation of neurohormonal
      factors. Although there was no significant difference in the pulmonary capillary
      wedge pressure or plasma atrial natriuretic peptide (ANP) level between the TCV
      116-treated groups (354 +/- 85 and 364 +/- 29 pg/ml for groups 1 and 2,
      respectively) and the vehicle group (385 +/- 20 pg/ml), the plasma guanosine
      3',5'-cyclic monophosphate (cGMP) levels, a second messenger of ANP, were twofold
      higher in TCV-116-treated groups (49.4 +/- 10.2 and 50.6 +/- 7.7 pmol/ml for
      groups 1 and 2, respectively) than in the vehicle group (24 +/- 4.0 pmol/ml),
      with a high correlation between the plasma ANP and cGMP levels (r = 0.90; P <
      0.05). These findings indicate that endogenous ANG II has important roles in
      hemodynamics and renal functions during the development of CHF, which may be due,
      in part, to a reduction in endogenous ANP activity, suggesting the usefulness of
      an ANG II-receptor antagonist against the development of CHF.

PMID- 9176281
TI  - Arteriolar constriction in skeletal muscle during vascular stunning: role of mast
      cells.
AB  - Striated muscle becomes stunned during reperfusion after sublethal ischemia.
      Resistance vessel tone and reactivity are altered in stunned muscle tissues. The
      hypothesis that adenosine-regulated mast cell degranulation occurs during
      reperfusion and leads to constriction of resistance arterioles was tested. The
      hamster cremaster muscle was subjected to 1 h of ischemia followed by
      reperfusion. Resistance arterioles constricted during reperfusion (74% of maximal
      diameter at baseline vs. 42% of maximal diameter after 30 min of reperfusion; P <
      0.01). Mast cells degranulated in reperfusion concomitant with arteriolar
      constriction. Stimulation of mast cell degranulation in control animals with
      compound 48/80 or cold superfusate (21 degrees C) caused vasoconstriction that
      mimicked that seen in reperfusion. The mast cell stabilizer cromolyn blocked
      degranulation and constriction. If mast cell granules were depleted by applying
      compound 48/80 before inducing ischemia, then arterioles failed to constrict
      during reperfusion. Adenosine A3-antagonist BW-A1433 abolished constriction.
      These findings suggest that arterioles constrict in reperfusion due to adenosine
      regulated mast cell degranulation. Vasodilation in response to sodium
      nitroprusside and acetylcholine was normal in stunned, constricted arterioles.
      However, the dose-response curves to adenosine were shifted to the left in
      arterioles constricted by either stunning, compound 48/80, exposure to cold
      superfusate, or cromolyn compared with control vessels. Depletion of granular
      components via stunning, compound 48/80, cold superfusate, or inhibition of
      secretion with cromolyn results in unopposed A1- or A2-mediated vasodilation in
      response to adenosine, whereas the dilatory effects of adenosine are blunted by
      simultaneous release of vasoconstrictors from mast cells in control animals. In
      summary, it was found that mast cell degranulation occurs during reperfusion and
      leads to constriction of resistance arterioles and altered vascular reactivity to
      adenosine. Adenosine is released in ischemia and stimulates mast cell
      degranulation via the A3 receptor located on mast cells during reperfusion.

PMID- 9176282
TI  - Inhibition by external Cd2+ of Na/Ca exchange and L-type Ca channel in rabbit
      ventricular myocytes.
AB  - We investigated the effect of external Cd2+ on the Na/Ca exchange and the L-type
      Ca channel current (ICa,L) in whole cell patch-clamped rabbit ventricular
      myocytes at 36 degrees C. After the interfering ion channels and the Na/K pump
      were blocked, the exchange current was measured as the membrane current that was
      inhibited by 5 mM nickel. External Cd2+ inhibited Na/Ca exchange with a
      dissociation constant (KD) of 320.6 +/- 12.4 microM and a Hill coefficient of 1.5
      +/- 0.09 (n = 13 cells) and ICa,L with a KD of 2.14 +/- 0.15 microM and a Hill
      coefficient of 0.74 +/- 0.03 (n = 11 cells). We observed some overlap in the Cd2+
      concentration that blocked each mechanism. Cd2+ (100-500 microM) is used commonly
      to block ICa,L completely. However, 100 microM Cd2+ also inhibits 20% of the
      Na/Ca exchange activity, whereas 500 microM Cd2+ inhibits 60%.

PMID- 9176283
TI  - Role of nitric oxide in vasodilator response induced by salbutamol in rat
      diaphragmatic microcirculation.
AB  - To determine the contribution of nitric oxide (NO) to the vasodilator response
      induced by salbutamol in diaphragmatic microcirculation, we studied a
      diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer
      solution continuously suffusing the diaphragm, laser-Doppler flowmetry was used
      to record microvascular blood flow (QLDF). The drugs were applied to the surface
      of the diaphragm. Salbutamol (3.2 x 10(-7)-10(-4) M), isoproterenol (3.2 x 10(-8)
      3.2 x 10(-6) M), and forskolin (3.2 x 10(-7)-10(-5) M) each elicited a
      concentration-dependent increase in QLDF. The vasodilator response induced by
      salbutamol (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was attenuated by a 15-min
      suffusion of N omega-nitro-L-arginine (L-NNA, 10(-4) M), and pretreatment with L
      arginine (10(-2) M) could restore salbutamol-induced vasodilator responses.
      Salbutamol-induced vasodilation was also abolished by propranolol (10(-5) M).
      Similarly, the vasodilator response elicited by isoproterenol (3.2 x 10(-8), 10(
      7), and 3.2 x 10(-7) M) and forskolin (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M)
      was inhibited by L-NNA (10(-4) M). In contrast, the vasodilator response induced
      by adenosine (10(-6), 10(-5), and 10(-4) M) was not affected by L-NNA (10(-4) M).
      These data indicate that in rat diaphragmatic microcirculation salbutamol-induced
      vasodilation may be partly mediated by beta-adrenoceptors on the endothelium.
      Moreover, these data suggest that an elevation of cyclic AMP in the endothelium
      may cause release of NO.

PMID- 9176284
TI  - Dynamic vagosympathetic interaction augments heart rate response irrespective of
      stimulation patterns.
AB  - We previously demonstrated that tonic stimulation of either the sympathetic or
      the vagal nervous system augmented the dynamic heart rate response to the other
      of the two systems. We characterized the phenomenon as bidirectional augmentation
      of heart rate regulation. The question remained unanswered, however, as to
      whether such augmentation could occur under simultaneous dynamic stimulation of
      the two systems. The transfer characteristics from nerve stimulation to heart
      rate were well described by linear systems analysis, although no attention was
      paid to the aphasic nature of the stimuli in relation to each R-R interval. When
      we stimulated the two nerves with statistically independent Gaussian white
      noises, gain of the transfer function increased by 63.2 +/- 47.4% relative to
      individual stimulation (P < 0.05). When we stimulated the two nerves with
      mutually reciprocal Gaussian white noises, gain of the transfer function
      increased by 54.9 +/- 49.1% (P < 0.05). Thus simultaneous dynamic stimulation of
      the sympathetic and vagal systems bidirectionally augmented heart rate regulation
      irrespective of the pattern of the stimulation signals.

PMID- 9176285
TI  - Factors inducing codistribution of marginal actin fibers and fibronectin in rat
      aortic endothelial cells.
AB  - Rat endothelial cells have a unique arrangement of actin fibers running with
      subendothelial fibronectin along the cell margins. The present study was
      conducted to identify the factors that are associated with codistribution of
      these actin fibers and fibronectin in fetal rat aortic endothelial cells, mainly
      using rheological techniques. Fluorescence histochemistry revealed that the
      codistribution pattern was established between gestational days 14 and 15. The
      endothelial cells changed from polygonal to spindle shaped during this
      gestational period. Although the aortic length remained almost unchanged during
      this period of gestation, both the diameter and expansion ratio of the aorta
      increased, by 9 and 10%, respectively. On the other hand, the wall shear rate
      increased rapidly during gestational days 13-16. These results indicate that the
      codistribution of actin fibers and subendothelial fibronectin along the margins
      of endothelial cells in fetal rat aorta occurs in association with a rise in
      stretch and shear stress and that the endothelial cells may require this change
      to maintain structural integrity.

PMID- 9176286
TI  - Cardiac contractile function during coronary stenosis in dogs: association of
      adenosine in glycolytic dependence.
AB  - We tested the hypothesis that during critical coronary stenosis, endogenous
      adenosine alters myocardial glucose utilization to support myocardial contractile
      function (MCF). Anesthetized mongrel dogs were instrumented to measure
      hemodynamic variables, regional MCF (sonomicrometry), and substrate uptakes.
      Critical coronary artery stenosis was established with a screw clamp on the left
      circumflex coronary artery (LCX). Either 8-phenyltheophylline (3 x 10(-7)
      mol/min; adenosine-receptor blockade), iodoacetate (1 x 10(-5) mol/min;
      glycolysis blockade), or vehicle was infused into the LCX and the left anterior
      descending coronary artery (LAD). Critical coronary stenosis caused small
      decreases in arterial blood pressure and LCX blood flow, but no significant
      changes in MCF or other hemodynamics. There was a significant decrease in the O2
      supply-to-consumption ratio in the stenotic region and an increased glucose
      uptake. Infusion of either 8-phenyltheophylline or iodoacetate caused a decrease
      in MCF in the stenotic LCX region concomitant with a decreased glucose uptake and
      without further changes in blood flow. This was not seen in the nonstenotic (LAD)
      region. These data support the hypothesis, indicating that glycolysis is vital
      for maintaining regional MCF during a decrease in the myocardial O2 supply-to
      consumption ratio and that adenosine is important in this regard, independent of
      its vasoactive properties.

PMID- 9176287
TI  - Involvement of AT2 receptors at NRVL in tonic baroreflex suppression by
      endogenous angiotensins.
AB  - We evaluated the role of endogenous angiotensin II and III (ANG II and ANG III)
      at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of
      baroreceptor reflex (BRR) response and the subtype of angiotensin receptors
      involved in this process. Adult male Sprague-Dawley rats anesthetized and
      maintained with pentobarbital sodium were used. Exogenous application of ANG II
      or ANG III (10, 20, or 40 pmol) by bilateral microinjection into the NRVL
      significantly suppressed the BRR response to transient hypertension induced by
      phenylephrine (5 micrograms/kg i.v.). The suppressive effect of ANG II (20 pmol)
      was reversed by an equimolar dose (1.6 nmol) of its peptide antagonist, [Sar1,
      Ile8]ANG II, and the nonpeptide antagonists for AT1 and AT2 receptors, losartan
      and PD-123319, respectively. On the other hand, the inhibitory action of ANG III
      (20 pmol) was blunted by its peptide antagonist. [Ile7]ANG III or PD-123319, but
      not by losartan. Blocking the endogenous activity of the angiotensins by
      microinjection into the bilateral NRVL of [Sar1, Ile8]ANG II, [Ile7]ANG III, or
      PD-123319 elicited an appreciable enhancement of the BRR response, whereas
      losartan produced minimal effect. These results suggest that, under physiological
      conditions, both endogenous ANG II and ANG III may exert a tonic inhibitory
      modulation on the BRR response by acting selectively on the AT2 receptors at the
      NRVL.

PMID- 9176288
TI  - Cardiac function in a rat model of chronic aortic stiffness.
AB  - Cardiac function was investigated in conscious normotensive rats in which
      increased aortic stiffness was produced as a result of vascular calcium overload
      after treatment with vitamin D3 plus nicotine (VDN rats, n = 16; controls, n =
      17). Baseline stroke volume, cardiac output, and cardiac response to a venous
      volume overload were unchanged after 1 mo of exposure to increased aortic
      stiffness, as were baseline venous return and total vascular capacitance. The
      latter was estimated from the change in mean circulatory filling pressure after
      modification of circulatory volume. Cardiovascular reflexes were modified in VDN
      rats. Bradycardia evoked by an increase in arterial PCO2 (PaCO2) or hypotensive
      hemorrhage was more pronounced. The PaCO2-induced bradycardia was accompanied by
      a fall in cardiac output in VDN rats but not in controls. In VDN rats, the
      attenuation of sympathetic reflexes may explain the slower recovery of blood
      pressure after hypotensive hemorrhage. In conclusion, a chronic increase in
      aortic stiffness does not compromise cardiac performance, but cardiovascular
      reflexes are impaired in VDN rats. Whether this is because of the increase in
      aortic stiffness or the effect of VDN treatment on the baroreceptors or other
      components of the reflex arc remains to be elucidated.

PMID- 9176289
TI  - Significance of TNF in hemorrhage-related hemodynamic alterations, organ injury,
      and mortality in rats.
AB  - To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in hemodynamic
      alterations, multiple organ damage, and mortality caused by hemorrhagic shock, we
      employed a monoclonal antibody to TNF-alpha (TNF-alpha MAb) in anesthetized rats
      subjected to prolonged hemorrhagic shock (mean arterial pressure of 30-35 mmHg
      for 180 min) followed by resuscitation over 50 min. Treatment of rats with 20.0
      mg/kg TNF-alpha MAb 15 min after the end of resuscitation significantly decreased
      the total peripheral resistance index (P = 0.031) and provided remarkable
      protection from multiple organ damage compared with controls. The 48-h survival
      rate was significantly higher in the treatment group (73.3%) than in the control
      group (26.7%; P = 0.029). The results suggest that TNF-alpha induced by
      hemorrhagic shock in rats is an important mediator of pathophysiological
      alterations associated with cardiovascular abnormalities, multiple organ injury,
      and even lethality. Postresuscitation treatment with TNF-alpha MAb, even after an
      initial TNF-alpha formation had occurred, significantly attenuated the
      cardiovascular consequences and improved the survival rate. Thus monoclonal
      antibodies to TNF-alpha might provide new prospects in the treatment of
      hemorrhage-related disorders.

PMID- 9176290
TI  - Cardiac autonomic control is inversely related to blood pressure variability
      responses to psychological challenge.
AB  - Blood pressure exhibits variability (BPV) at low (0.02- to 0.07-Hz), mid (0.07-
      to 0.15-Hz)-, and high (0.15- to 0.50-Hz) frequencies. Evidence suggests that BPV
      responses to challenge are inversely related to cardiac autonomic control. We
      tested this hypothesis by examining the BPV responses to psychological stressors
      in 22 normal subjects who differed in cardiac control, operationalized as resting
      heart period variability (HPV). HPV and BPV were measured noninvasively or a beat
      to-beat basis. The stressors produced a significant increase in heart rate and a
      small but significant increase in diastolic blood pressure. As predicted, the
      changes in BPV in response to the stressors were inversely related to resting
      HPV. The results are interpreted in terms of a model of cardiovascular control
      that holds that BPV originates from feedforward effects of central control of the
      heart, feedback effects mediated through the baroreflexes, and direct sympathetic
      vascular effects.

PMID- 9176291
TI  - Oxygen tension gradients and heterogeneity in venous microcirculation: a
      phosphorescence quenching study.
AB  - Localized measurements of intravascular oxygen tension (PO2) at multiple
      locations in the microvascular network of the rat spinotrapezius muscle were used
      to study the spatial distribution of PO2 in venular structures. By use of a newly
      developed phosphorescence system to rapidly and repeatedly measure PO2, 538
      individual measurements were made in 18 different networks during rest. Average
      intravascular PO2 was (in mmHg +/- SD) 33 +/- 9, 21 +/- 9, 26 +/- 10, and 33 +/-
      8 in small arcade arterioles, postcapillary venules (PV), 3 degrees venules (3V),
      and arcade venules, respectively. The coefficient of variation (CV), a
      descriptive indicator of spatial heterogeneity, was correspondingly 0.28, 0.45,
      0.37, and 0.23 for the different vessel groups. PO2 was found to increase
      significantly (P < 0.001) from PV to 3V, rising 0.009 +/- 0.002 mmHg/microns
      along the vessel. By linear regression, the slope of PO2 for the vessel
      difference group, PV-3V as a function of mean systemic blood pressure (BPm; in
      mmHg) was -0.09 +/- 0.04 (P < 0.05), indicating that the measured longitudinal
      oxygen gradients and CV are only weakly dependent on BPm. The results support the
      hypothesis that oxygen can diffuse across the walls of postcapillary vessels and
      suggest that the venular structures are not merely passive conduits for removing
      oxygen and waste products but may play an important role in regulating oxygen
      delivery.

PMID- 9176292
TI  - KCa-channel blockade prevents sustained pressure-induced depolarization in rat
      mesenteric small arteries.
AB  - In small blood vessels, elevation of transmural pressure induces myogenic
      constrictions and smooth muscle depolarization. The role of calcium-activated K+
      channels (KCa channels) in these responses was examined in cannulated rat
      mesenteric small arteries. Inner and outer diameter were continuously monitored
      with a video technique. Smooth muscle membrane potential was recorded
      simultaneously using microelectrodes. To test for myogenic responsiveness, the
      transmural pressure was changed stepwise in the range between 10 and 120 mmHg.
      Pressure elevation induced moderate myogenic responses and significant
      depolarization, from -54.5 +/- 0.4 (SE) mV (n = 56) at 10 mmHg to -47.3 +/- 1.8
      mV (n = 12) at 120 mmHg. Norepinephrine (NE, 0.67 and 10 microM) induced
      constriction and vasomotion, augmented myogenic responsiveness, and shifted the
      pressure-membrane potential relation to more depolarized values. Blockade of the
      Kca channels with charybdotoxin (ChTX) suppressed the responsiveness to pressure.
      In the absence of ChTX, with 0.67 microM NE, pressure elevation from 10 to 120
      mmHg induced depolarization from -46.9 +/- 1.0 (n = 16) to -35.8 +/- 0.7 (n = 12)
      mV, whereas because of the myogenic response, the diameter increased only by 7%.
      In the presence of ChTX, with 0.3 microM NE, pressure changed the membrane
      potential from -41.0 +/- 1.1 (n = 12) to -37.8 +/- 0.7 mV (n = 4), which was not
      significant, and the diameter increased by 28%. These results demonstrate that
      blockade of KCa channels reduces responsiveness to pressure elevation. This
      suggests that pressure may induce depolarization and concomitant myogenic
      responsiveness by closure of KCa channels.

PMID- 9176293
TI  - Pulmonary distribution of iodoantipyrine: temperature and lipid solubility
      effects.
AB  - In multiple indicator-dilution studies in rat and dog lungs, we have found that
      the distribution of iodoantipyrine (IAP) is not limited by the endothelium at a
      temperature > 7 degrees C but is barrier limited at the epithelium at a
      temperature < 15 degrees C (permeability coefficient of 6.3 x 10(-5) cm/s at 8
      degrees C). IAP extraction from the vascular surface to the tissues is greater
      than those of antipyrine (AP) and tritiated water (THO). IAP transmittance from
      the alveolar surface to the vascular compartment is smaller than those of AP and
      THO: a lung lipid compartment, probably in the lamellar bodies of the type II
      cells, is more accessible to IAP than to AP or THO because IAP has a higher oil
      to-water distribution coefficient. Our mathematical model takes into account
      these matters and also the low surface density of the type II cells: some of the
      IAP may bypass the lipid compartment. Lipid may affect the transit of solutes
      with high oil-to-water distribution coefficients in the lungs and across the
      alveolar-capillary barrier.

PMID- 9176294
TI  - Estrogen replacement attenuates resistance artery adrenergic sensitivity via
      endothelial vasodilators.
AB  - The objective of this study was to determine whether chronic estrogen replacement
      alters adrenergic constriction and endothelium-dependent dilation in resistance
      arteries from the rat. Resistance-sized (< 200 microns) mesenteric arteries from
      castrated female Sprague-Dawley rats with (E2; 21 day, 0.5-mg pellet) and without
      (OvX) estrogen replacement were removed for in vitro study on a pressurized
      arteriograph system. Sensitivity to alpha-adrenergic constriction and the role of
      the endothelium in its modulation and of agonist-provoked endothelium-dependent
      relaxation were determined. Estrogen-treated rats had decreased heart rate as
      well as systolic and diastolic blood pressure. Arteries from estrogen-replaced
      rats were fivefold less sensitive to alpha 1-adrenergic stimulation with
      phenylephrine (50% effective concentration: E2, 3.2 +/- 1.1 microM; OvX, 0.6 +/-
      0.2 microM; P < 0.05). This difference was abolished by endothelial denudation,
      blockade of cyclooxygenase (1 microM ibuprofen), or nitric oxide synthase
      blockade (0.24 mM N omega-nitro-L-arginine). There was no difference in
      muscarinic agonist-provoked relaxation or vascular smooth muscle sensitivity to
      prostacyclin or sodium nitroprusside. These results indicate that estrogen
      replacement decreases resistance artery adrenergic sensitivity by increasing the
      basal release of relaxing factors from the endothelium. This effect on small
      artery function may produce dual cardioprotective effects by decreasing
      peripheral resistance, blood pressure, and the likelihood of thrombosis.

PMID- 9176295
TI  - Physiological variations in ovine cerebrovascular calcium sensitivity.
AB  - Cerebrovascular reactivity to biogenic amines varies in relation to both arterial
      diameter and age. The present study examines the hypothesis that these patterns
      of reactivity are secondary to corresponding variations in the Ca2+ sensitivity
      of the contractile proteins. To test this hypothesis, we permeabilized segments
      of common carotid (Com), basilar, main branch middle cerebral, and second-branch
      middle cerebral (MCA-B) arteries from nonpregnant adult and near-term fetal sheep
      using beta-escin. Permeabilization methods were carefully validated and adjusted
      for each artery type. Baseline myofilament Ca2+ sensitivity in both adults and
      fetuses increased significantly from the Com to the MCA-B and was generally
      higher in fetuses than in adults. Serotonin dose dependently increased Ca2+
      sensitivity via a G protein-dependent mechanism in all arteries. The magnitudes
      of this effect did not vary among artery types but were significantly greater in
      fetal than in adult arteries. This effect of serotonin was mimicked by guanosine
      5'-O-(3-thiotriphosphate), a nonhydrolyzable analog of guanosine 5'-triphosphate,
      and its effects were also much greater in fetal than in adult arteries. We
      conclude that patterns of cerebrovascular reactivity to biogenic amines were
      determined, at least in part, by underlying variations in baseline myofilament
      Ca2+ sensitivity and/or its alteration by G protein-dependent mechanisms.

PMID- 9176296
TI  - Role of endogenous centrally released NO in cardiovascular adaptation to
      hypovolemia in WKY and SHR.
AB  - The role of endogenous centrally released nitric oxide (NO) during hypovolemia
      was investigated in normotensive Wistar-Kyoto (WKY) and spontaneously
      hypertensive rats (SHR). Bleeding of the rats (1.3% of blood volume) was
      performed after intracerebroventricular (ICV) administration of: 1) artificial
      cerebrospinal fluid (series 1, time control, 8 WKY and 8 SHR); 2) 0.5 mg NG-nitro
      L-arginine (L-NNA, 2.3 nmol), an inhibitor of NO synthesis (series 2, 8 WKY and 7
      SHR); and 3) 0.5 mg L-NNA followed by 1 mg (5.8 nmol) of L-arginine (L-Arg) (6
      WKY and 5 SHR). In WKY, hypotension was associated with significant bradycardia
      (P < 0.001), whereas in SHR slight acceleration of heart rate was observed. In
      series 2 hemorrhage resulted in a small but significant increase of mean arterial
      pressure (MAP; P < 0.05) and considerable tachycardia (P < 0.001). In SHR, L-NNA
      did not modify the decrease of MAP during hypovolomia, and bleeding resulted in a
      significant bradycardia (P < 0.001). Pretreatment with L-Arg in series 3 was able
      to reverse the effects of L-NNA on changes of MAP and heart rate during
      hypovolemia. The results indicate that the central nitroxidergic system plays a
      significant role in eliciting hypotension and bradycardia in normotensive WKY
      during hemorrhage. Function of the central nitroxidergic system is significantly
      altered in SHR in which NO appears to prevent hemorrhagic bradycardia and to
      reduce the hypotensive effect.

PMID- 9176297
TI  - Effect of phasic vagal stimulation and atrial pacing site on atrioventricular
      conduction time.
AB  - We tested the hypothesis that the effect of phasic vagal stimulation on
      atrioventricular (AV) conduction time is affected by the site of atrial pacing in
      anesthetized dogs. We paced the right atrium at a constant cycle length from the
      interatrial septum (IAS), superior coronary sinus (SCS), or inferior coronary
      sinus (ICS) regions, and we evaluated the time-dependent effects of vagal
      stimulation on AV conduction at each pacing site. When we stimulated the vagi at
      stimulus (St)-A phases greater than 136 +/- 40 ms and less than the phase that
      blocked AV conduction (182 +/- 70 ms), IAS pacing prolonged A-V intervals by 8.6
      +/- 8.2 ms more than ICS pacing. A change in pacing site affected the A-V
      intervals by up to 30 ms when we stimulated the vagus at those times that caused
      the A-V intervals to prolong maximally. Furthermore, the effect of atrial pacing
      site on A-V intervals was modulated by AV nodal recovery times during the second
      or third cycles after the vagal stimulus.

PMID- 9176298
TI  - Biaxial mechanics of the passively overstretched left ventricle.
AB  - Overstretching the intact ventricle increases global compliance as a function of
      maximum previously experienced load and may have an important role in the
      diseased heart, but the corresponding changes in local myocardial mechanics and
      structure are unknown. Therefore, we measured two-dimensional strain on the left
      ventricular (LV) epicardium in isolated arrested rat hearts sequentially inflated
      to increasing cavity pressures of 10, 30, and 120 mmHg. Strains at matched LV
      pressures increased significantly (P < 0.002) as the maximum pressure previously
      experienced by the LV (Pmax) increased. Compared with Pmax = 10 mmHg, relative
      increases in fiber strain for Pmax = 30 and 120 mmHg (100 and 149%, respectively)
      were significantly greater (P < 0.001) than the corresponding increases in cross
      fiber (51 and 78%, respectively) and fiber shear (57 and 86%, respectively)
      strains. Using an optimized prolate spheroidal finite-element model of the rat LV
      that reliably reproduced experimental strains, we estimated progressive decreases
      in epicardial biaxial wall stiffness up to 87% with increasing Pmax that were not
      different in the fiber and cross-fiber directions. Thus, although passive
      ventricular overloading causes direction-dependent increases in epicardial
      strain, these changes are the consequence of local myocardial softening that is
      actually independent of direction.

PMID- 9176299
TI  - Effect of K(+)-channel blockers on ACh-induced hyperpolarization and relaxation
      in mesenteric arteries.
AB  - Acetylcholine (ACh) induces endothelium-dependent hyperpolarization in the rat
      mesenteric artery in the presence of the nitric oxide synthase inhibitor N omega
      nitro-L-arginine. We have now studied the effects of K(+)-channel blockers on the
      hyperpolarization responses to ACh in resting and norepinephrine-contracted rat
      mesenteric arteries. We also measured tension simultaneously to determine whether
      the inhibitory effects of these agents on relaxation could be correlated to their
      effects on hyperpolarization. Glibenclamide had no significant effect on the
      hyperpolarization or relaxation. Tetraethylammonium (TEA, 5 mM) inhibited the
      hyperpolarization to ACh significantly to a similar extent in both the resting
      and norepinephrine-stimulated arteries. Charybdotoxin (100-150 nM) caused only a
      small but significant inhibition. Apamin (0.3 microM) was the most effective in
      inhibiting the hyperpolarization in resting arteries. It was less effective in
      the norepinephrine-contracted arteries. A combination of apamin and charybdotoxin
      completely abolished the hyperpolarization responses in both conditions. The
      relaxation to ACh was correlated to hyperpolarization. In all cases, the
      inhibition of the relaxation by the K(+)-channel blockers could be accounted for
      by their effects on the hyperpolarization. These results indicate that Ca(2+)
      activated K(+)-channels, especially those sensitive to apamin, may be the major
      ion channels mediating endothelium-dependent hyperpolarization to ACh.

PMID- 9176300
TI  - Increased cardiomyocyte apoptosis during the transition to heart failure in the
      spontaneously hypertensive rat.
AB  - The transition from compensated hypertrophy to failure in spontaneously
      hypertensive rats (SHR) of advanced age is associated with a marked increase in
      collagen, a reduction in myocyte mass, and a reduction in maximum Ca(2+)
      activated myofibrillar force. We hypothesized that the reduction in myocyte mass
      and associated functional loss may be due to increased cell death by apoptosis.
      To test this hypothesis, we studied hearts from failing (SHR-F) and nonfailing
      SHR (SHR-NF) and age-matched Wistar-Kyoto rats (WKY). In addition, hearts from
      SHR-F that had been treated with an angiotensin-converting enzyme inhibitor
      (captopril) for an average of 27 days were also studied. Apoptotic cells were
      quantified in cross sections of myocardium by the terminal
      deoxynucleotidyltransferase- mediated 2'-deoxyuridine 5'-triphosphate nick end
      labeling technique. To identify the type of the cells undergoing apoptosis,
      sections were also stained for alpha-sarcomeric actin. Apoptotic cells were
      significantly increased in the SHR-F (38.92 +/- 12.79 vs. 8.05 +/- 3.98
      cells/100,000 nuclei in SHR-NF; P < 0.05 and vs. 2.21 +/- 1.4 cells/100,000
      nuclei in WKY; P < 0.01). Captopril treatment of SHR-F reduced the number of
      apoptotic cells to the level in SHR-NF (9.17 +/- 1.53 cells/100,000 nuclei; P <
      0.01 vs. SHR-F). Most apoptotic cells were of cardiac myocyte origin. There was
      no significant difference in Bcl-2 protein expressed by hearts among the three
      groups. WAF-1 mRNA levels were increased in both SHR groups vs. WKY; in SHR-F,
      the density of WAF-1 mRNA was higher than in SHR-NF. Thus increased numbers of
      apoptotic cells are present in failing SHR hearts, suggesting that apoptosis
      might be a mechanism involved in the reduction of myocyte mass that accompanies
      the transition from stable compensation to heart failure in this model.
      Administration of the angiotensin-converting enzyme inhibitor captopril, which
      ameliorates heart failure in this model, is associated with a reduction in the
      exaggerated apoptosis that accompanies heart failure.

PMID- 9176301
TI  - Effects of contraction, perfusion pressure, and length on intramyocardial
      pressure in rat papillary muscle.
AB  - If intramyocardial pressure (IMP) is the pressure that causes coronary flow to
      stop, i.e., "backpressure," then it should be equal to the zero-flow perfusion
      pressure intercept (Pzf). Therefore we determined Pzf and IMP at zero flow
      (IMPzf) in papillary muscles suspended isometrically in a bath, superfused with a
      well-oxygenated Tyrode solution (27 degrees C), and perfused with Tyrode solution
      via the septal artery. For the IMP (servo-null) measurements, we used unbeveled
      glass micropipettes with a tip diameter of 3-4 microns. During diastolic arrest
      and systolic contracture (2 mM Ba21), perfusion pressure steps were applied, and
      the corresponding flow and IMP values were recorded. Fitting of the
      relationships, yielded Pzf and IMPzf. In the diastolically arrested muscle,
      perfusion pressure affected IMP. Pzf was much higher in systolically contracted
      muscle than in diastolically arrested muscle. The IMPzf in both conditions was
      significantly smaller than Pzf. Thus, even in this preparation with no
      ventricular pressure, IMP increases during contraction. We conclude that IMP
      arises from contraction per se but is not the pressure that causes the flow to
      stop.

PMID- 9176302
TI  - Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia
      reperfusion injury in rats.
AB  - In the present study, the contribution of nitric oxide (NO), superoxide, and
      peroxynitrite to the inflammatory response induced by myocardial ischemia
      reperfusion (MI/R) was investigated. Male Sprague-Dawley rats were anesthetized,
      and the left main coronary artery was ligated for 20 min and reperfused for 5 h.
      MI/R induced severe arrhythmias, indicated by a significantly elevated arrhythmia
      score in the MI/R group compared with that in the sham control group. Creatine
      kinase activity in the left ventricular free wall of the MI/R group was
      significantly reduced by 38%. In contrast, myeloperoxidase activity in the left
      ventricular free wall of the MI/R group was increased by 140%. Similarly,
      superoxide and tissue NO levels in the ischemic region of the heurt were
      increased by 140 and 90%, respectively. Superoxide and NO values in the
      nonischemic regions were similar to the sham control group. Total NO synthase
      (NOS) activity was elevated by 212%; moreover, inducible NOS (iNOS) activity
      increased 6.7-fold in the ischemic vs. nonischemic regions. MI/R also induced
      both systemic and remote organ (lung) inflammatory responses. Circulating
      neutrophils and plasma NO levels were increased by 163 and 138%, respectively, in
      MI/R rats compared with sham control animals. NO levels and superoxide generation
      were increased by 90 and 176%, respectively, in the lung tissues. The expression
      of iNOS and peroxynitrite generation were demonstrated by immunohistochemical
      staining with polyclonal anti-iNOS and monoclonal anti-nitrotyrosine antibodies,
      respectively. Sections of both the ischemic area of the ventricular wall and the
      lung tissue of MI/R animals exhibited a marked immunoreactivity with anti-iNOS
      and anti-nitrotyrosine antibodies, indicating the presence of iNOS and
      nitrotyrosine. Our data indicate that NO, superoxide, and peroxynitrite formation
      are elevated after reperfusion of the ischemic heart, suggesting that these
      inflammatory mediators may be involved in MI/R injury.

PMID- 9176303
TI  - Effect of nicotine on endothelium-dependent arteriolar dilatation in vivo.
AB  - Smoking is a primary risk factor in coronary and peripheral vascular disease.
      However, the precise component of cigarette smoke that contributes to the
      pathogenesis of vascular disease remains unclear. The goal of this study was to
      determine the effect of nicotine on endothelium-dependent dilatation of
      peripheral resistance arterioles in vivo. We measured the diameter of resistance
      arterioles (approximately 50 microns in diameter) contained within the
      microcirculation of the hamster cheek pouch in response to endothelium-dependent
      (acetylcholine and ADP) and -independent (nitroglycerin) agonists before and
      after an intravenous infusion of vehicle or two concentrations of nicotine.
      Acetylcholine, ADP, and nitroglycerin produced a dose-related dilatation of the
      cheek pouch arterioles under control conditions. Endothelium-dependent, but not 
      independent, dilatation of arterioles was modestly impaired by an infusion of a
      low concentration of nicotine (1.0 microgram.kg-1.min-1). Infusion of a higher
      concentration of nicotine (2 micrograms.kg-1.min-1), which increased the plasma
      level of nicotine to 14 +/- 1.6 ng/ml, produced a profound selective impairment
      in endothelium-dependent vasodilatation. We suggest that elevations in plasma
      nicotine may contribute to the pathogenesis of the peripheral vascular disease
      observed in smokers.

PMID- 9176304
TI  - Modeling of arterial and cardiopulmonary baroreflex control of heart rate.
AB  - We evaluated R-R interval changes (delta R-R interval) in 13 subjects (27 +/- 6
      yr; 7 men and 6 women) as a function of blood pressure changes at the carotid
      sinus and aortic arch and central venous pressure changes at the cardiopulmonary
      receptors. Neck chamber pressure and suction were used to change pressure at the
      carotid sinus while lower body negative pressure, phenylephrine infusion, and
      nitroprusside infusion were used to change pressure at the carotid sinus (delta
      CSP), aortic arch (delta AAP), and cardiopulmonary receptors (delta CPP). Random
      effects regression analysis showed a significant linear relationship for delta R
      R interval (-1.75 + 1.64 delta CSP + 15.40 delta AAP + 29.02 delta CPP + error),
      and the correlation (r) between the observed and predicted delta R-R interval was
      0.82 (P < 0.00001). Sixty-seven percent of the delta R-R interval variability
      observed in the study is explained by the model. delta AAP accounts for
      approximately 63%, delta CSP for 14%, and delta CPP for 23% of the explained
      delta R-R interval.

PMID- 9176305
TI  - Endothelin-1 in rat endotoxemia: mRNA expression and vasoreactivity in pulmonary
      and systemic circulations.
AB  - Endothelin-1 (ET-1) is a vasoconstrictor and proinflammatory peptide, but its
      role in the vascular response to sepsis is unknown. After intraperitoneal
      injection of male Wistar rats (300 g) with 20 mg/kg of Salmonella enteritidis
      lipopolysaccharide (LPS), the expression of ET-1 mRNA was significantly increased
      in pulmonary artery and aorta within 1 h and arterial ET-1 concentration was
      elevated. Despite this increase in ET-1 production, there was no difference in
      baseline systemic or pulmonary arterial pressures between control and endotoxin
      treated rats, and, furthermore, combined ETA/ETB receptor antagonism using
      bosentan produced reductions in systemic and pulmonary arterial pressures that
      were not greater than the modest fall seen in controls. However, bosentan
      completely antagonized the hemodynamic effects of exogenous ET-1 in controls but
      only weakly antagonized its effects in LPS animals. After LPS the initial (ETB
      mediated) systemic hypotensive responses to ET-1 were attenuated, but the
      subsequent systemic pressor responses were not. By contrast, the increases in
      pulmonary arterial pressure in response to ET-1 and the ETB receptor agonist
      sarafotoxin S6c were significantly reduced in LPS animals. Vascular ET-1 mRNA
      expression and arterial ET-1 concentration are elevated after LPS treatment in
      rats, but the functional activity of ET-1 cannot be exposed by combined ETA/ETB
      receptor antagonism, possibly because of an alteration in the functional status
      of ET receptors.

PMID- 9176306
TI  - Stereoselective actions of S-nitrosocysteine in central nervous system of
      conscious rats.
AB  - This study examined whether the stereoselective actions of S-nitrosocysteine
      (SNC) in the central nervous system involves the activation of stereoselective
      SNC recognition sites. We examined the effects produced by
      intracerebroventricular injection of the L- and D-isomers of SNC (L- and D-SNC)
      on mean arterial blood pressure, heart rate, and vascular resistances in
      conscious rats. We also examined the hemodynamic effects produced by
      intracerebroventricular injections of 1) L-cystine, the major non-nitric oxide
      (NO) decomposition product of L-SNC, 2) the parent thiols L- and D-cysteine, and
      3) the bulky S-nitrosothiol L-S-nitroso-gamma-glutamylcysteinylglycine [L-S
      nitrosoglutathione, (L-SNOG)]. Finally, we examined the decomposition of L- and D
      SNC and L-SNOG to NO on their addition to brain homogenates. The
      intracerebroventricular injection of L-SNC (250-1,000 nmol) produced falls in
      mean arterial pressure, increases in heart rate, and a dose-dependent pattern of
      changes in hindquarter, renal, and mesenteric vascular resistances. The
      intracerebroventricular injections of D-SNC, L-cystine, and L-SNOG produced only
      minor effects. The intracerebroventricular injection of L-cysteine produced
      pressor responses and tachycardia, whereas D-cysteine was inactive. L- and D-SNC
      decomposed equally to NO on addition to brain homogenates. L-SNOG decomposed to
      similar amounts of NO as L- and D-SNC. These results suggest that SNC may
      activate stereoselective SNC recognition sites on brain neurons and that S
      nitrosothiols of substantially different structure do not stimulate these sites.
      These recognition sites may be stereoselective membrane-bound receptors for which
      L-SNC is the unique ligand.

PMID- 9176307
TI  - Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the
      hindlimb of the rat.
AB  - Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic
      noncholinergic vasodilator system. The aim of this study was to determine whether
      this vasodilator system may represent postganglionic lumbar sympathetic neurons
      that synthesize and release nitric oxide (NO) or related NO-containing factors.
      We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves
      innervate the hindlimb vasculature of the rat and whether the hindlimb
      vasodilation produced by electrical stimulation of the lumbar sympathetic chain
      of anesthetized rats is reduced after the systemic administration of the specific
      inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar
      sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and
      varicosities within the iliac and femoral arteries also stained for NOS. Double
      ligation of the lumbar chain demonstrated that NOS was transported from the cell
      bodies toward the peripheral terminals. Low-intensity electrical stimulation of
      the lumbar chain produced a pronounced hindlimb vasodilation that was markedly
      diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the
      vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7
      NI. These results suggest that postganglionic lumbar sympathetic neurons may
      synthesize and release NO-containing factors.

PMID- 9176308
TI  - Purine nucleotides contribute to pulmonary vasodilation caused by birth-related
      stimuli in the ovine fetus.
AB  - We investigated the hypothesis that the purine nucleotides ATP and adenosine
      mediate the pulmonary vasodilation that occurs at birth in fetal lambs. We
      instrumented 44 fetal lambs to measure left pulmonary arterial pressure and flow.
      In control studies, we investigated the effects of sequential ventilation with
      10, 50, and 100% O2 on fetal pulmonary arterial pressure and flow and pulmonary
      vascular resistance (PVR). We also measured the blood and plasma ATP levels in
      the pulmonary artery and left atrium in the control studies. In three separate
      groups of studies, we investigated the effects of 8-phenyltheophylline, an
      adenosine-receptor antagonist, and cibacron blue, an inhibitor of ATP-sensitive
      P2y receptors, given alone or in combination, on the response of PVR to
      sequential ventilation. Fetal arterial PO2 increased during ventilation with 50
      and 100% O2 but not with 10% O2. Ventilation with 10% O2 caused a 4-fold increase
      in pulmonary blood flow and a 10-fold decrease in PVR. Ventilation with 50 and
      100% O2 caused a 7-fold increase in pulmonary blood flow and a 20-fold decrease
      in PVR. Blood and plasma ATP levels in the pulmonary artery and blood ATP levels
      in the left atrium increased significantly during ventilation with 50 and 100% O2
      but not with 10% O2. Pretreatment of animals with 8-phenyltheophylline attenuated
      the increase in pulmonary flow and decrease in PVR caused by ventilation at all
      fractions of inspired O2 (FIO2 levels). Pretreatment of animals with cibacron
      blue attenuated pulmonary vasodilation at 50 and 100% FIO2. Combined treatment
      with 8-phenyltheophylline and cibacron blue caused complete inhibition of the
      decrease in PVR in response to ventilation at the three FIO2 levels. Incubation
      of fetal red blood cells in vitro with 100% O2 caused an increase in ATP
      production. An increase in arterial PO2 in the fetus causes an increase in blood
      ATP levels, and an inhibition of ATP receptors attenuates the O2-induced decrease
      in PVR. Adenosine-receptor inhibition attenuates both ventilation- and O2-induced
      changes in PVR. Increased synthesis and release of ATP plays a major role in
      causing pulmonary vasodilation in response to birth-related stimuli in the ovine
      fetus.

PMID- 9176309
TI  - Expression of a recombinant preproendothelin-1 gene in arteries stimulates
      vascular contractility.
AB  - Endothelin (ET)-1 is a potent vasoconstrictor peptide that is elevated in
      cardiovascular diseases. However, the biological function of ET-1 gene expression
      within arteries in vivo has not been determined. The effects of ET-1 gene
      expression were investigated using gene-transfer methods on porcine vascular
      cells in vitro and porcine arteries in vivo. Transfection of vascular cells with
      a vector encoding for human preproendothelin-1 cDNA (pVR-ppET) resulted in
      significant increase in active ET-1 levels in culture supernatant compared with
      nontransfected cells (P < 0.05). This supernatant contracted rat aortic strips at
      concentrations 10-fold lower than synthetic ET-1 protein, which was inhibited by
      the ET-A receptor antagonist BQ-123. Transfection of pVR-ppET into pig
      iliofemoral arteries resulted in an increase in contractile responses to
      angiotensin I compared with control vessels (P < 0.05), in contrast to serotonin,
      phenylephrine, synthetic ET-1, and angiotensin II. A mitogenic effect of
      recombinant ET-1 on intimal cell growth was not observed. These findings
      demonstrate that expression of a recombinant ET-1 gene in vivo augments vascular
      contractility due to an increased sensitivity to angiotensin I, suggesting a role
      for ET-1 in the pathogenesis of cardiovascular diseases.

PMID- 9176310
TI  - Gated magnetic resonance imaging of normal and hypertrophied murine hearts.
AB  - Transgenic murine models are being used increasingly to explore the molecular
      basis of heart disease. Until recently, there were no means for noninvasive
      assessment of changes in mass and function of the murine heart because of its
      very small size and high heart rate. Transthoracic echocardiography has now been
      utilized to obtain noninvasive estimates of murine left ventricular (LV) wall
      thicknesses, internal dimension, and mass. However, this approach is based on one
      dimensional (M-mode) measurements of the LV at its midwall that take no account
      of variations in LV chamber and wall dimensions along other minor axes and at
      other anatomic levels. Thus asymmetries in LV geometry, which can affect LV mass
      estimates, may be undetected. In this study, gated (diastolic) magnetic resonance
      imaging (MRI) was utilized to obtain two-dimensional images of the LV at four
      anatomic levels in intact, anesthetized mice. In 17 normal CD-1 mice (body mass,
      18-47 g; gravimetric LV mass, 51-135 mg), LV mass estimates produced from the MRI
      data correlated well (r = 0.87) with LV mass determined gravimetrically. In
      addition, this approach identified changes in LV mass and wall thickness-to
      chamber diameter ratio in a group of seven aortic-constricted mice (body mass, 32
      39 g; gravimetric LV mass, 119-198 mg) with compensated and decompensated LV
      hypertrophy. These findings suggest that utility of MRI for serial, noninvasive
      assessment of experimentally induced alterations in mass and geometry of the
      murine heart.

PMID- 9176311
TI  - Effect of chronic myocardial infarction on in vivo reactivity of skeletal muscle
      arterioles.
AB  - The first goal of this study was to test the hypothesis that chronic myocardial
      infarction alters reactivity of rat skeletal muscle arterioles in vivo. At 4, 8,
      and 16 wk after induction of chronic myocardial infarction or sham (control)
      surgery, the spinotrapezius muscle was prepared for direct visualization of the
      microcirculation. Responses of third-order arterioles (37.9 +/- 0.9 microns) were
      measured after topical suffusion of acetylcholine (ACh; 0.1, 1.0, and 10 microM),
      calcitonin gene-related peptide (CGRP; 0.01, 0.1, and 1.0 nM), substance P (SP;
      0.01, 0.1, and 1.0 microM), and sodium nitroprusside (SNP; 1.0, 10, and 100
      microM). Arteriolar reactivity was impaired after chronic myocardial infarction
      in response to ACh and CGRP at all time periods examined. In contrast,
      vasodilatation in response to SP and SNP was preserved after 4, 8, and 16-wk of
      chronic myocardial infarction. The second goal of this study was to explore the
      possibility that impaired arteriolar reactivity during chronic myocardial
      infarction may be related to an altered availability of L-arginine (L-Arg).
      Suffusion of L-Arg (1.0 mM) partially restored impaired ACh- and CGRP-induced
      responses in myocardial-infarcted animals toward that observed in controls. Thus
      the present study demonstrates that impaired reactivity of skeletal muscle
      arterioles during chronic myocardial infarction appears to be partially related
      to an alteration in L-Arg availability.

PMID- 9176312
TI  - Response of native and stimulated collateral vessels to serotonin.
AB  - Previous studies suggest that collateral vessels constrict in response to
      serotonin. The objective of these studies was to directly measure responses of
      native and stimulated collateral vessels 30-400 microns in diameter to serotonin
      and to determine the mechanisms involved in responses to serotonin. Serotonin was
      suffused onto the left ventricle of dogs, and microvascular diameters were
      measured with computer-controlled stroboscopic illumination coupled to a
      microscope-video system. Stimulated collateral vessels and arterioles in
      collateral-dependent myocardium were measured after Ameroid constriction of the
      left circumflex artery. Noncollateral and native collateral vessels were examined
      in dogs without a constrictor. Serotonin produced dose-dependent dilation of
      noncollateral vessels that was decreased in native collateral vessels, stimulated
      collateral vessels, and vessels in collateral-dependent myocardium. Dilation in
      response to nitroprusside was similar in all groups. Dilation in response to
      serotonin was enhanced by inhibition of 5-hydroxytryptamine (5-HT)2 receptors
      with ketanserin and blocked by nonselective 5-HT1 and 5-HT2 receptors with
      methiothepin. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine
      decreased dilation in response to serotonin. Thus collaterals and arterioles in
      collateral-dependent myocardium are less sensitive to the dilating effect of
      serotonin. Responses to serotonin involve a balance between dilation mediated by
      5-HT1 receptors and constriction mediated by 5-HT2 receptors.

PMID- 9176313
TI  - Downregulation of sarcoplasmic reticulum Ca(2+)-ATPase during progression of left
      ventricular hypertrophy.
AB  - To determine whether reduced sarcoplasmic reticulum (SR) Ca(2+)
      adenosinetriphosphatase (ATPase) (SERCA2) activity contributes to delayed
      myocardial relaxation during chronic left ventricular hypertrophy (LVH)
      progression, LVH was produced in rats by abdominal aortic coarctation. Systolic
      and diastolic functions were assessed in vivo 8 and 16 wk after surgery, and
      compositional alterations in LV myocardium [SERCA2 concentration, myosin heavy
      chain (MHC) isoenzymes, and tissue collagen] were correlated with the development
      of prolonged isovolumic relaxation and impaired cardiac performance over time.
      Myocardial relaxation was prolonged in 8-wk banded rats, despite normal
      isovolumic systolic function and LV end-diastolic pressure (LVEDP). No
      significant alterations in SERCA2 protein, beta-MHC, or fibrillar collagen levels
      were observed at this early time point. In contrast, LV SERCA2, beta-MHC, and
      fibrillar collagen concentrations were all significantly altered in 16-wk banded
      rats. These late compositional changes were associated with reduced cardiac
      performance, as manifested by a significant elevation in LVEDP (14 +/- 2 mmHg).
      The 34% decrease in SERCA2 protein was associated with reduced SR Ca2+ uptake and
      an even greater reduction (76%) in SERCA2 mRNA. SERCA2 mRNA levels were also
      significantly reduced to 43 +/- 10% of sham-operated rats 8 wk after banding,
      despite unchanged SERCA2 protein levels and normal SR Ca2+ uptake. These results
      argue against a significant contribution of SERCA2 downregulation to the subtle
      alterations in myocardial relaxation observed in compensated LVH. However, the
      early reduction in SERCA2 mRNA levels may serve as a molecular marker for
      impaired cardiac performance during the transition from compensated LVH to heart
      failure.

PMID- 9176314
TI  - Cardiac myocyte volume, Ca2+ fluxes, and sarcoplasmic reticulum loading in
      pressure-overload hypertrophy.
AB  - Alterations in cellular Ca2+ transport and excitation-contraction coupling may
      contribute to dysfunction in cardiac hypertrophy. Left ventricular myocytes were
      isolated from rat hearts after 15-18 wk of suprarenal abdominal aortic banding to
      evaluate the hypothesis that hypertrophy alters the relationship between Ca2+
      current (ICa) and sarcoplasmic reticulum (SR) Ca2+ load during steady-state
      voltage-clamp depolarization. Mean arterial pressure (MAP) and heart weight-to
      body weight ratio of banded (B) animals were significantly higher than in control
      or sham-operated animals (C). Isolated myocyte dimensions and volume increased in
      parallel with whole heart hypertrophy and elevation in MAP. However, the
      relationship between membrane surface area (measured by capacitance) and cell
      volume (measured by laser scanning confocal microscopy) was unaltered (C: 8.9 +/-
      0.3; B: 8.5 +/- 0.4 pF/pl). No differences in the voltage dependence of ICa
      activation, steady-state inactivation, or recovery from inactivation were
      detected between C and B myocytes. Maximal ICa density for the two groups was
      also not different either under basal conditions (C: 4.28 +/- 0.98; B: 4.57 +/-
      0.60 pA/pF) or in the presence of 1 microM isoproterenol (C: 16.6 +/- 2.3; B:
      16.5 +/- 2.3 pA/pF). The fraction of Ca2+ released from the SR by a single twitch
      was 55.4 +/- 9.4% in C and 37.1 +/- 6.9% in B (not significantly different).
      Steady-state Ca2+ influx during a twitch was calculated in units of micromoles
      per liter of nonmitochondrial volume from the integral of ICa (C: 13.4 +/- 0.7
      microM; B: 13.3 +/- 0.8 microM). The SR Ca2+ load was similarly calculated by
      integration of Na+/Ca2+ exchange current induced by rapid caffeine application
      (C: 140 +/- 9 microM; B: 169 +/- 18 microM). We conclude that significant
      cellular hypertrophy is associated with proportional increases in sarcolemmal ICa
      influx, SR Ca2+ loading, and the amount of SR Ca2+ released in this model of
      pressure overload.

PMID- 9176315
TI  - Chronic hypoxia inhibits postnatal maturation of porcine intrapulmonary artery
      relaxation.
AB  - Neonatal pulmonary hypertension is associated with increased pulmonary vascular
      reactivity. We studied the responses of isolated porcine intrapulmonary arteries
      after exposure of piglets to chronic hypobaric hypoxia (CHH) from 0 to 2.5, 3 to
      6, or 14 to 17 days of age. CHH inhibited the postnatal development of
      endothelium-dependent vasorelaxation to acetylcholine (ACh) and the calcium
      ionophore A-23187. Basal accumulation of guanosine 3', 5'-cyclic monophosphate
      (cGMP) was unaffected, but cGMP response to ACh was inhibited. Endothelium
      independent relaxation to nitric oxide (NO) and zaprinast (a phosphodiesterase
      inhibitor) was also inhibited, but cGMP accumulation in response to these
      agonists was normal. The ability of sodium nitroprusside (SNP) to cause
      vasorelaxation and increase cGMP accumulation was unaffected. Contractile
      responses to potassium chloride and prostaglandin F2 alpha (PGF2 alpha) were
      similar to normal after exposure from birth and 3 days and were decreased in the
      older group, but the ability of NG-monomethyl-L-arginine acetate to increase PGF2
      alpha-induced contractions decreased. Thus exposure of newborn piglets to CHH
      causes 1) no increase in contractile responses and 2) impairment of endothelium
      dependent and -independent relaxation by impairing signal transduction mechanisms
      involved in the release of NO and the effectiveness of cGMP.

PMID- 9176316
TI  - Inhibition of NO synthesis minimally affects the dynamic baroreflex regulation of
      sympathetic nerve activity.
AB  - The purpose of this investigation was to examine the role of nitric oxide (NO) in
      the dynamic baroreflex regulation of cardiac sympathetic nerve activity. In
      anesthetized rabbits, we imposed random pressure perturbations on the isolated
      carotid sinuses before and after the intravenous administration of NG-monomethyl
      L-arginine. We characterized the dynamic properties relating carotid sinus
      pressure input to sympathetic nerve activity by means of a transfer function
      analysis. NG-monomethyl-L-arginine decreased the corner frequency of the transfer
      function (0.100 +/- 0.054 vs. 0.074 +/- 0.035 Hz; P < 0.05), whereas other
      parameters such as the steady-state gain and transmission lag time remained
      unchanged. Although cursory examination of these findings would suggest a
      possible contribution of NO in the dynamic baroreflex regulation of sympathetic
      nerve activity, quantitative assessment of the transfer function reveals only a
      minimal effect on the baroreflex regulation of arterial pressure, particularly
      under closed-loop conditions. We conclude that NO noticeably affects the dynamic
      baroreflex regulation of sympathetic nerve activity. However, it may not
      significantly affect arterial pressure regulation through central modulation of
      the carotid sinus baroreflex.

PMID- 9176317
TI  - Physical and physiological determinants of pulmonary venous flow: numerical
      analysis.
AB  - To study the physical and physiological determinants of transmitral and pulmonary
      venous flow, a lumped-parameter model of the cardiovascular system has been
      created, modeling the instantaneous pressure, volume, and influx/efflux of the
      pulmonary veins, left atrium and ventricle, systemic arteries and veins. right
      atrium and ventricle, and pulmonary arteries. Initial validation has been
      obtained by direct comparison with transesophageal echocardiographic recordings
      of mitral and pulmonary venous velocity for the following clinical situations:
      normal diastolic function, delayed ventricular relaxation, restrictive filling
      due to severe systolic dysfunction, severe mitral regurgitation before and after
      valve repair surgery, and premature atrial contraction occurring during
      ventricular systole. Sensitivity analysis has been performed with a Jacobian
      matrix, representing the proportional change in a group of output indexes (yi) in
      response to isolated changes in input parameters (xj), [(delta yi/yi)/ ([delta
      xj/xj)], demonstrating the complementary nature of mitral and pulmonary venous A
      wave velocity for predicting ventricular stiffness and atrial systolic function.
      This unified numerical-experimental programming environment should facilitate
      model refinement and physiological data exploration, in particular guiding more
      accurate interpretations of Doppler echocardiographic data.

PMID- 9176318
TI  - Laminar structure of the heart: a mathematical model.
AB  - A mathematical description of cardiac anatomy is presented for use with finite
      element models of the electrical activation and mechanical function of the heart.
      The geometry of the heart is given in terms of prolate spheroidal coordinates
      defined at the nodes of a finite element mesh and interpolated within elements by
      a combination of linear Lagrange and cubic Hermite basis functions. Cardiac
      microstructure is assumed to have three axes of symmetry: one aligned with the
      muscle fiber orientation (the fiber axis); a second set orthogonal to the fiber
      direction and lying in the newly identified myocardial sheet plane (the sheet
      axis); and a third set orthogonal to the first two, in the sheet-normal
      direction. The geometry, fiber-axis direction, and sheet-axis direction of a dog
      heart are fitted with parameters defined at the nodes of the finite element mesh.
      The fiber and sheet orientation parameters are defined with respect to the
      ventricular geometry such that 1) they can be applied to any heart of known
      dimensions, and 2) they can be used for the same heart at various states of
      deformation, as is needed, for example, in continuum models of ventricular
      contraction.

PMID- 9176319
TI  - Noninvasive analysis of renal artery blood flow dynamics with MR cine phase
      contrast flow measurements.
AB  - It was the aim of this study to quantify the measurement of pulsatile flow in the
      renal artery with the noninvasive magnetic resonance cine phase-contrast (MRCPC)
      method and combine it with the simultaneous assessment of pulsatile flow with a
      transit-time ultrasound (TTUS) flowmeter. In seven foxhounds with a chronically
      implanted precalibrated TTUS flow probe, MRCPC flow measurements were made in the
      renal artery with a temporal resolution of 32 ms. Mean and pulsatile flow signal
      were compared by the simultaneous ipsi- or contralateral measurement of the renal
      blood flow signal by both methods (TTUS and MRCPC). In addition, comparative
      MRCPC and TTUS flow measurements were made with artificial renal artery stenosis
      and after the administration of angiotensin II. The mean flow data assessed by
      the noninvasive MRCPC flow measurements showed an excellent correlation with
      corresponding TTUS recording (r = 0.99). The MRCPC flow signal displayed a
      waveform of the renal artery flow profile that was very similar to the TTUS flow
      pulse. The hemodynamic changes induced by angiotensin II or due to renal artery
      stenosis were also reliably detected by MRCPC. MRCPC provides a reliable
      noninvasive method for the quantification of mean blood flow and the assessment
      of the pulsatile flow signal in the renal artery and proves to be sensitive to
      hemodynamic changes of pathophysiological importance. Alternatively, the method
      may be used for studies in physiology that demand a noninvasive approach.

PMID- 9176320
TI  - Do adult rat ventricular myocytes express protein kinase C-alpha?
AB  - Although calcium-insensitive protein kinase C (PKC) isoforms (PKC-epsilon and PKC
      delta) are consistently detected in adult ventricular myocytes, the evidence that
      adult ventricular myocytes also express calcium-sensitive PKC-alpha is
      inconsistent. The current study used four different anti-PKC-alpha-antibodies to
      resolve some of the uncertainties regarding the immunodetection of PKC-alpha in
      adult ventricular myocytes. Three of the antibodies used in this study barely
      (GIBCO-BRL) or rather faintly (Transduction Laboratories and Seikagaku America)
      recognize PKC-alpha in crude preparations from adult ventricular myocytes.
      Although each of these antibodies recognizes a prominent 80-kDa band, which is
      similar in size to PKC-alpha, this represents nonspecific immunoreactivity and
      should not be confused with PKC-alpha. This conclusion is based on peptide
      blocking experiments (GIBCO-BRL), the absence of the requisite sensitivity to
      calcium- and phorbol 12-myristate 13-acetate-induced translocation (Seikagaku
      America and Transduction Laboratories), and/or the failure to copurify with PKC
      alpha on DEAE-Sephacel chromatography. Nevertheless, an antibody from Upstate
      Biotechnology clearly recognizes PKC-alpha and not other unrelated nonspecific
      immunoreactive species in crude preparations from adult ventricular myocytes.
      Each of the antisera used in this study could detect PKC-alpha immunoreactivity
      following chromatographic purification of the samples to enrich for PKC-alpha and
      remove nonspecific immunoreactive proteins. These results suggest that PKC-alpha
      is expressed by adult ventricular myocytes and argue that differences in the
      sensitivity and/or specificity of available antisera contribute to at least some
      of the confusion regarding PKC-alpha expression in adult ventricular myocytes.

PMID- 9176321
TI  - Use of oxygen-15 to measure oxygen-carrying capacity of blood substitutes in
      vivo.
AB  - A method for determining oxygen-carrying capacity of blood substitutes has been
      developed using the short-lived cyclotron-produced positron-emitting isotope 15O.
      This method measures the oxygen-carrying capacity of the blood substitutes in
      vivo in the presence of red blood cells and allows determination of changes in
      the oxygen-carrying capacity over time after exchange transfusion. This method is
      applied to the blood substitutes of liposome-encapsulated hemoglobin (LEH) and
      cell-free hemoglobin (Hb). We have used 15O (half-life of 2 min) to quantitate
      the lung uptake and tissue delivery of [15O2]LEH. Lung uptake studies were
      performed in intubated, catheterized rats after a 40% exchange transfusion of
      bovine LEH (LEBH; 0.68 g Hb/kg body wt), human hemolysate LEH (LEHH; 1.0 g Hb/kg
      body wt), or free bovine hemoglobin (SFHS; 0.56 g Hb/kg body wt). A bolus
      inhalation of 15O2 (3-5 mCi) was given at 15 min, 3 h, and 24 h post-transfusion.
      Arterial blood samples were collected, spun, and separated into LEH, red blood
      cell, and plasma fractions. 15O activity and hemoglobin content were determined
      for each fraction. Oxygen-carrying capacity was calculated as a percentage of the
      original red blood cell fraction removed. For LEBH, the carrying capacity was 15%
      at 15 min, 13% at 3 h, and 1% at 24 h. For LEHH, the carrying capacity was 30% at
      15 min, 26% at 3 h, and 19% at 24 h. The marked decrease in carrying capacity at
      24 h for LEBH compared with LEHH was attributable to the increased formation of
      methemoglobin in the circulating LEBH rather than increased removal from
      circulation, because total hemoglobin concentrations measured for both LEH
      samples decreased at a similar rate during the 24 h. The presence of
      methemoglobin reductase and other naturally occurring antioxidants in the LEHH
      may be responsible for maintaining the higher levels of oxyhemoglobin. Oxygen
      carrying capacity for SFHS also decreased over time but at a much sharper rate
      compared with both LEH formulations. The carrying capacity for SFHS of 8%
      measured at 15 min decreased to 0.3% at 3 h and undetectable levels at 24 h. This
      sharper decrease in carrying capacity for SFHS is attributable to the rapid
      removal of the hemoglobin from circulation.

PMID- 9176322
TI  - A chloride current component induced by hypertrophy in rat ventricular myocytes.
AB  - The effect of hypertrophy on membrane currents of rat left ventricular myocytes
      was studied with the whole cell voltage-clamp method. We found that the slope of
      the total time-independent current density-voltage relationship was increased in
      hypertrophied cells. No change in the zero-current potential was observed.
      Surprisingly, the dominant time-independent current, the inward rectifier K+
      current (measured as the Ba(2+)-sensitive current density) was unchanged. We
      therefore investigated the identity of the outwardly rectifying Ba(2+)-resistant
      current seen in the hypertrophied rat ventricular myocytes but not present in
      control cells. We found that this current 1) was not carried by monovalent
      cations, 2) was partially blocked by anthracene-9-carboxylic acid (9-AC), and 3)
      was sensitive to variations in extracellular Cl concentration. These findings are
      consistent with the current being carried at least partially by Cl-. The presence
      of an additional Cl(-)-dependent component in hypertrophied cells is supported by
      the actions of 9-AC on the measured action potentials (APs). 9-AC had no effect
      on control cells APs but prolonged hypertrophied cell APs. We conclude that a Cl-
      current component develops in hypertrophied rat heart cells. This component
      appears to shorten the AP duration and might thus provide protection from cardiac
      arrhythmias.

PMID- 9176323
TI  - Characterization of ATP-sensitive potassium channels in freshly dissociated
      rabbit aortic endothelial cells.
AB  - ATP-sensitive potassium (KATP) channels represent a class of K+ channel regulated
      by intracellular ATP and serve to transduce changes in cell metabolism into
      changes in membrane potential. The presence of an KATP conductance has recently
      been demonstrated in freshly dissociated endothelial cells from rabbit arteries.
      In the present study, the single-channel activity underlying the KATP conductance
      in rabbit aortic endothelial cells was examined. Unitary currents were evoked in
      response to lowering intracellular ATP concentration or application of the K(+)
      channel activator levcromakalim and were inhibited by the sulfonylurea drug
      glibenclamide. Exposure of the cytoplasmic face of an inside-out membrane patch
      to a solution containing 0.1 mM ATP produced single-channel events with unitary
      conductances of approximately 150 and approximately 25 pS that were inhibited by
      either 6 mM ATP or 10 microM glibenclamide. A small conductance channel was also
      activated in cell-attached patches by bath-applied levcromakalim (25 microM).
      Activation of endothelial cell KATP channels, and subsequent membrane
      hyperpolarization, may contribute to endothelium-dependent regulation of vascular
      smooth muscle tone in response to changes in levels of intracellular metabolites.

PMID- 9176324
TI  - Macula densa stimulation of renin is reversed by selective inhibition of neuronal
      nitric oxide synthase.
AB  - The neuronal isoform of nitric oxide synthase (nNOS) exists in the renal cortex
      predominantly in the macula densa, suggesting that nitric oxide (NO) derived from
      the macula densa plays a role in feedback regulation of renin in response to
      altered sodium metabolism. To determine if nNOS is a critical component in renin
      stimulation induced by dietary sodium restriction, rats received either normal
      sodium or a sodium-restricted diet (0.03%) for 7 days and subsequently were or
      were not treated with the selective inhibitor of nNOS 7-nitroindazole (7-NI)
      either acutely (50 mg/kg body wt ip) on the final day or chronically (20 mg/kg
      body wt ip 2 x/day) over the final 5 days. On the last day, rats were
      anesthetized with Inactin and fitted with arterial and renal venous catheters to
      collect blood and monitor blood pressure (BP) and a flow probe to measure renal
      blood flow (RBF). BP (105 vs. 108 mmHg) was similar in normal and low-sodium
      dietary groups, respectively, whereas RBF tended to be higher in the sodium
      restricted group (6.5 +/- 0.3 vs. 7.6 +/- 0.4 ml.min-1.g kidney wt-1). Both renal
      venous renin (RR) and renin secretion rate (RSR) were elevated approximately
      fourfold by sodium restriction [RR = 5.8 +/- 0.8 vs. 20.5 +/- 2.7 ng angiotensin
      (ANG) I.ml-1.h-1; P < 0.001; RSR = 3.0 +/- 0.9 vs. 13.1 +/- 4.1 ng ANG I.h-1.min
      1; P < 0.025]. Acute 7-NI did not change BP, RR, or RSR, but reduced RBF in
      sodium-restricted rats by 8% (P < 0.05). Chronic 7-NI had no effect on renin in
      rats on a normal diet, but reduced RR by one-half in the sodium-restricted group
      (to 9.9 +/- 1.6 ng ANG I-ml-1.h-1; P < 0.001) and reduced RSR to normal (diet)
      levels (to 3.9 +/- 1.4 ng ANG I.h-1.min-1; P < 0.05). Although selective NOS
      inhibition by 7-NI did not affect BP, RBF, or renin in control rats on a normal
      diet, chronic 7-NI reversed the stimulation of renin induced by dietary sodium
      restriction. These data suggest that nNOS-derived NO plays an important role in
      the macula densa during feedback stimulation of renin induced by dietary sodium
      restriction.

PMID- 9176325
TI  - Dysregulation of arcuate nucleus preproneuropeptide Y mRNA in diet-induced obese
      rats.
AB  - Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) produce
      metabolic and physiological effects that promote the development and maintenance
      of obesity. In turn, NPY metabolism in these neurons is inhibited by dopamine
      release. In this study, ARC prepro-NPY mRNA and ARC/median eminence (ME) dopamine
      turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet
      induced obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE)
      diet. By in situ hybridization, DIO-prone rats had 39% more ARC NPY mRNA
      expression than DR-prone rats under chow-fed conditions. DIO-prone rat ARC/ME
      dopamine levels were 14% higher, but dopamine half-life was 176% longer and
      turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy
      intake restriction for 5 days affected the already increased ARC NPY mRNA levels
      in DIO-prone rats. Both manipulations increased NPY expression to the level of
      DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE
      diet for 2 wk, neither DIO- nor DR-prone rats altered their ARC NPY expression
      despite the development of obesity and hyperinsulinemia in DIO rats. Thus DIO
      prone rats overexpress and fail to regulate ARC NPY mRNA to energy restriction or
      hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition
      because of defective ARC/ME dopamine turnover. Both may be important predisposing
      factors in the development of DIO.

PMID- 9176326
TI  - Presynaptic sympathetic mechanism in the insulinostatic effect of epinephrine in
      mouse pancreatic islets.
AB  - The catecholamines inhibit insulin release. It is not established whether
      presynaptic mechanisms contribute to this effect. We therefore examined the
      relative contribution of presynaptic and postsynaptic mechanisms to the
      insulinostatic effects of epinephrine and norepinephrine. Mice were injected with
      6-hydroxydopamine (6-OHDA; 0.19 mmol/kg) or its vehicle. Islets were isolated
      after 48 h. Islets from vehicle-injected control animals contained numerous
      tyrosine hydroxylase (TH)-immunoreactive nerve terminals (marker for sympathetic
      nerves). In contrast, TH-immunoreactive nerves were not detected in islets from 6
      OHDA-treated animals, indicating sympathetic denervation. Basal (5.6 mmol/l
      glucose) or glucose-stimulated (16.7 mmol/l) insulin secretion did not differ
      between incubated islets from vehicle-injected control animals and islets from 6
      OHDA-treated animals. The insulinostatic effect of epinephrine, but not that of
      norepinephrine, was markedly impaired in islets from 6-OHDA-treated animals: the
      lowest effective insulinostatic concentration of epinephrine was 0.01 nmol/l in
      islets from vehicle-injected animals and 1 nmol/l in islets from 6-OHDA-treated
      animals. We conclude that in isolated mouse islets the insulinostatic effect of
      epinephrine, but not that of norepinephrine, partially depends on sympathetic
      nerve terminals, suggesting an important role for presynaptic mechanisms in
      epinephrine-induced inhibition of insulin secretion.

PMID- 9176327
TI  - Effects of A-23187 and verapamil on the active transport enzymes in turtle
      bladder epithelial cells.
AB  - These experiments were designed to examine the effects of A-23187 (5 x 10(-4) M)
      and verapamil (100 microM) on membrane transport, 45Ca fluxes, and adenosine
      triphosphatase (ATPase) activities in turtle bladder. In the intact membrane, the
      calcium ionophore decreased proton secretion and sodium transport [short-circuit
      current (SCC)] to approximately the same degree (by approximately 55% at 30 min).
      During the same period of time, verapamil decreased SCC (by approximately 58%),
      but proton secretion was unaffected. The turtle bladder membrane is composed
      predominantly of two cell types: 1) the mitochondrial-rich cells (MR cells)
      thought to be involved in proton (and bicarbonate) secretion containing
      significant H(+)-ATPase and Ca(2+)-ATPase and 2) the granular cells (G cells),
      postulated important in sodium reabsorption, having abundant Na(+)-K(+)-ATPase.
      That Na(+)-K(+)-ATPase activity was unchanged by either a calcium ionophore or a
      calcium channel blocker suggests that the decrease in SCC noted in the intact
      membrane is not directly mediated by changes in the sodium "pump." The decrease
      of H(+)-ATPase in MR cells, which resulted after the A-23187, suggests that it
      probably exerts a direct action on the proton pump, which decreases hydrogen ion
      secretion. The increase in ATP-dependent 45Ca transport seen after the ionophore
      (or the decrease in ATP-independent 45Ca transport after verapamil) most likely
      reflects increased (or decreased) Ca2+ availability within the cytosol, and the
      high (or low) cell calcium could decrease the SCC. These results thus suggest
      that cytosolic Ca2+ reciprocally sets, by different mechanisms, the rate of
      proton secretion in MR cells and the sodium reabsorption in G cells.

PMID- 9176328
TI  - Regulated hypothermia in the hypothyroid rat induced by administration of
      propylthiouracil.
AB  - Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4)
      and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by
      impairing metabolic thermogenesis. However, it is not understood why PTU-treated
      animals cannot use behavioral and other thermoeffectors to maintain normal Tc.
      Male rats were administered PTU in drinking water (0.05 mg/ml) while the
      following parameters were measured: 1) Tc and motor activity (MA) recorded by
      radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2)
      selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming
      behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU
      reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased
      after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout
      the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a
      consistent hypothermic Tc during the light phase; however, a deficit in the
      stability of Tc at night was noted during exposure to 10 degrees C. In the
      temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at
      the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C.
      Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of
      the PTU rats was maintained below 38 degrees C. The regulation of Tc at
      hypothermic levels over a wide range of Ta values and when rats were housed in a
      temperature gradient indicates that chronic PTU induces a state of regulated
      hypothermia.

PMID- 9176329
TI  - Substance P decreases fluid absorption in the renal proximal tubule.
AB  - Substance P is a neuropeptide found principally in the central nervous system and
      peripheral afferent nerve fibers. It is widely distributed in the body, and its
      local release is thought to have important effects in the normal physiology and
      pathophysiology of several organ systems. Substance P releases histamine from
      mast cells and nitric oxide from endothelial cells. Systemic infusion of
      substance P causes a brisk natriuresis. Previously, proximal tubule transport in
      the kidney was measured in vivo during the infusion of substance P. Transport was
      inhibited. This could have been a direct action of substance P or secondary to
      the release of histamine or nitric oxide. Therefore, we have now studied the
      effect of substance P on isolated proximal tubules perfused in vitro. We found
      that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption
      in rabbit proximal straight tubule. This effect was reversible on removal of
      substance P from the bath. Inhibition of nitric oxide production with NG
      monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at
      10(-10) M. The sensitivity of the proximal tubule to low concentrations of
      substance P, together with the recent findings of substance P-containing afferent
      fibers within the cortex of the kidney, suggest a role for substance P in the
      control of proximal tubule reabsorption, particularly in pathophysiological
      conditions associated with increased afferent nerve activity, such as ureteric
      occlusion.

PMID- 9176330
TI  - Role of Na(+)-K+ pump and Na+ channel concentrations in the contractility of rat
      soleus muscle.
AB  - The dependence of contractile performance on the leak-to-pump ratio for Na+ has
      been examined. In isolated rat soleus muscle the concentration of Na(+)-K+ pumps
      was shown to decrease with age (-57%) or K+ deficiency (-69%), whereas Na+
      channel concentration remained constant. This relative increase in the ratio
      between Na+ channels and Na(+)-K+ pumps was associated with a markedly faster
      rate of force decline (58 and 97%, respectively; both P < 0.001) during
      stimulation at 90 Hz and reduced subsequent force recovery (-34 and -38%,
      respectively; both P < 0.001). Similar effects were elicited by acute inhibition
      of Na(+)-K+ pump activity with ouabain. Preincubation with aconitine and
      veratridine, resulting in a 91 and 118% increase in Na+ influx per contraction,
      respectively (both P < 0.05), significantly hastened the initial rate of force
      decline (19%; P < 0.05 for aconitine and 69%; P < 0.001 for veratridine) and
      slowed recovery (-59 and -86%, respectively, both P < 0.001). It is concluded
      that the ratio between excitation-induced Na+ influx and Na(+)-K+ pump capacity
      is an important determinant for endurance and rate of recovery of force in
      skeletal muscle.

PMID- 9176332
TI  - Hard training for 5 mo increases Na(+)-K+ pump concentration in skeletal muscle
      of cross-country skiers.
AB  - To study how training affects the Na(+)-K+ pump concentration, 11 male and 9
      female elite junior cross-country skiers trained 12-15 h/wk at 60-70% (moderate
      intensity group) or 80-90% (high-intensity group) of their maximal O2 uptake for
      5 mo. Muscle biopsies taken from the vastus lateralis muscle before and after the
      training period were analyzed for Na(+)-K+ pump concentration by the [3H]ouabain
      binding technique. Before training, the concentration was 343 +/- 11 nmol/kg wet
      muscle mass (mean +/- SE) for the men and 281 +/- 14 nmol/kg for the women (18%
      less than for the men, P = 0.003). The Na(+)-K+ pump concentration rose by 49 +/-
      11 nmol/kg (16%, P < 0.001) for all subjects pooled during the training period,
      and there was no difference between the two training groups (P = 0.3) or the
      sexes (P = 0.5) in this increase. The Na(+)-K+ pump concentration correlated with
      the maximal O2 uptake (r = 0.6, P = 0.003), with the performance during a 20-min
      treadmill run (r = 0.6, P = 0.003), and to the rank of the subjects' performance
      as cross-country skiers (Spearman's rank correlation coefficient = 0.76, P <
      0.001). These data could mean that for elite cross-country skiers the performance
      is related to the Na(+)-K+ pump concentration. However, other studies have shown
      an equally high pump concentration for far less fit subjects, suggesting that the
      pump concentration may not be a limiting factor.

PMID- 9176331
TI  - Effects of artificial calculosis on rat ureter motility: peripheral contribution
      to the pain of ureteric colic.
AB  - The contribution of changes in ureter motility produced by a stone to the pain of
      ureteric calculosis is unclear. In this study we measured ureter motility as
      changes in intraureter pressure in anesthetized rats 1, 4, and 8 d ys after
      implantation of an artificial calculus (n = 33) and compared it with motility in
      normal (n = 8) and ligated (n = 4) ureters. Partial obstruction of the ureter by
      the stone produced a 478% increase in the amplitude of contractions, a 70%
      decrease in the rate of contractions, and a 66% decrease in the baseline
      pressure. The pressures reached during contractions were equivalent to those
      evoking nociceptive reactions in animals and humans. These changes persisted in
      rats that had spontaneously eliminated the stone. Complete obstruction of the
      ureter by the stone or by ligation abolished contractions. We conclude that the
      increased motility caused by a stone likely contributes to the development and
      maintenance of visceral pain and referred hyperalgesia in ureteric colic and to
      the persistence of referred hyperalgesia after elimination of the stone.

PMID- 9176333
TI  - Spinal Fos labeling and penile erection elicited by stimulation of dorsal nerve
      of the rat penis.
AB  - Penile afferents present in the dorsal nerve of the penis (DNP) convey sensory
      information from the penis to the spinal cord and represent the afferent limb of
      reflexive erections. Immunocytochemical staining of Fos was used to identify
      spinal neurons that receive excitatory inputs from the DNP in anesthetized rats.
      Intracavernous pressure (ICP) was recorded as an index of erection. Dissection as
      well as stimulation of the DNP elicited a comparable increase in Fos staining.
      Labeling was present in the dorsal horn, the dorsal gray commissure, and the
      sacral parasympathetic nucleus, supporting the hypothesis of direct or indirect
      afferent projection from the penis and penile sheath in these areas. No change in
      ICP was observed in these rats. Stimulation of the DNP elicited both increased
      Fos labeling and ICP after spinalization, demonstrating the presence of a
      supraspinal inhibitory control exerted on the polysynaptic intraspinal circuitry
      responsible for reflexive penile erection.

PMID- 9176334
TI  - Sarcolemmal Ca influx through L-type Ca channels in ventricular myocytes of a
      teleost fish.
AB  - The whole cell patch clamp method was used to measure Ca current through L-type
      Ca channels in enzymatically isolated ventricular myocytes of crucian carp
      (Carassius carassius L.) heart. Fish were acclimated to 22 degrees C for more
      than 4 wk, and properties of Ca current were measured at room temperature (21 +/-
      1 degrees C). Depolarizing voltage steps from -50 mV evoked rapidly activating Ca
      currents, which exhibited a bell-shaped voltage dependence with peak amplitude at
      0 mV. The currents were suppressed by nifedipine (5 microM), verapamil (2.5
      microM), and Cd2+ (175 microM). The current amplitude was increased by 67.5 +/-
      17.2% (n = 5) in the presence of 1 microM isoproterenol. Steady-state
      inactivation and activation curves showed half-maximal inactivation at -31.3 +/-
      0.95 mV, with a slope factor of 5.88 +/- 0.51, and half-maximal activation at 
      10.6 +/- 1.65 mV, with a slope factor of 7.84 +/- 0.54 (n = 9). The overlap of
      inactivation and activation curves suggests the presence of a small window
      current, which is maximally 4% of the peak current at -27 mV. The density of L
      type Ca current was 6.95 +/- 0.79 pA/pF at 0 mV (n = 35). A total increment in
      cellular Ca contributed by L-type Ca current during a 500-ms voltage clamp pulse
      was calculated from the integral of Ca current and cell volume. The charge
      transfer through L-type Ca current was 0.325 +/- 0.023 pC/pF, and the mean cell
      volume was 1,377 +/- 44 microns3. The increment in total cellular Ca by Ca influx
      through L-type Ca channels was calculated to be 39.3 +/- 2.8 microM. These
      findings imply that Ca influx through L-type Ca channels can contribute
      significantly to the activation of contraction in the ventricular myocytes of
      fish heart.

PMID- 9176335
TI  - Effects of antisense oligodeoxynucleotides on peptide release from
      hypothalamoneurohypophysial explants.
AB  - Rapid effects of antisense oligodeoxynucleotides (AODNs) on the function of the
      neurohypophysial system have been reported previously. The present studies were
      designed to determine the effects of vasopressin (VP) and oxytocin (OT) AODNs on
      osmotically or potassium-stimulated VP and OT release from perifused
      hypothalamoneurohypophysial (HNS) explants. The AODNs were 18-mer
      phosphorothioate forms targeted toward the translation initiation sites of either
      VP or OT mRNA, or a mixed base sequence (4 microM). The explants were exposed to
      a ramp increase in NaCl (either 20 or 30 mosmol/6 h) or to 25 mM KCl. VP and OT
      release was measured by radioimmunoassay in sequential 20-min fractions of the
      perifusate. There was a peptide-specific inhibition by the AODNs of osmotically
      stimulated VP and OT release. VP AODN inhibited VP, but not OT release, and vice
      vorsa. However, the AODNs had no effect on potassium-stimulated peptide release,
      demonstrating that depolarization-secretion coupling was still intact.
      Furthermore, there were no significant differences in VP and OT mRNA and peptide
      content after antisense treatment. Thus these observations indicate that acute
      exposure to peptide AODNs interrupts osmotically stimulated VP and OT release in
      a peptide-specific manner.

PMID- 9176336
TI  - Central nitric oxide donors attenuate cardiovascular and central norepinephrine
      responses to stress.
AB  - An earlier study showed that norepinephrine (NE) was released in the
      paraventricular nucleus (PVN) and posterior hypothalamus (PH) along with
      increases of mean arterial pressure (MAP) and heart rate (HR) during shaker
      stress (SS). Here we investigated the possibility that nitric oxide (NO) donors,
      infused into hypothalamus, could modulate responses to SS. In conscious rats, an
      injector-microdialysis probe, for direct application of donor and collection of
      extracellular NE, respectively, was inserted into PVN or PH; MAP and HR were
      recorded continuously from conscious rats. The NO donor, molsidomine (Mol),
      infused 5 or 30 min before SS, did not alter baseline values of NE, MAP, or HR,
      but did attenuate changes elicited by 5 min of SS; methylene blue blocked the
      effects of Mol. The NO donor, sodium nitroprusside, was much less effective than
      Mol as a modulator of stress-related effects. The results indicate that MAP, HR,
      and hypothalamic NE responses to environmental stress, but not baseline values,
      can be modulated by NO donors in the hypothalamus.

PMID- 9176337
TI  - Intake suppression after hepatic portal glucose infusion: all-or-none effect and
      its temporal threshold.
AB  - The effects of hepatic portal infusions of isotonic glucose on glucose intake
      (3.2%) were evaluated with use of the intraoral intake test, which, unlike
      traditional tests, permits delivery of portal infusions in explicit temporal
      relationship to intake onset in nondeprived rats. Continuous or discontinuous
      portal infusions (0.1 ml/min) of isotonic glucose or saline were initiated 0, 30,
      60, or 120 min before meal onset. Jugular infusions of isotonic saline or glucose
      and portal infusions of isotonic saline were without effect. For all effective
      portal glucose infusions, intake was suppressed by approximately 30% of baseline
      values. Because the duration (and quantity) of effective portal glucose infusions
      varied by a factor of 10, we conclude that intraoral intake suppression under
      these conditions is all or none in nature. Whether an intake suppression was
      obtained depended more on when the infusion was delivered than on how much was
      infused. Thus 1.5 ml of isotonic glucose infused between 60 and 45 min before the
      intake test was effective, whereas 3.0 ml infused for the 30 min before intake
      was without effect. These results suggest that the liver participates in the
      control of future intake but not in the termination of an ongoing meal. The
      temporal requirement for intake suppression should be considered in analyses of
      the metabolic, hormonal, and/or neural mechanisms that underlie the liver's
      contribution to intake control.

PMID- 9176338
TI  - Food intake alters muscle protein gain with little effect on Na(+)-K(+)-ATPase
      and myosin isoforms in suckled rats.
AB  - Biochemical maturation accompanies the rapid accretion of skeletal muscle in
      early life. We wished to determine whether changes in muscle protein accretion,
      induced by variations in food intake, altered the biochemical maturation of the
      soleus and the extensor digitorum longus (EDL) muscles. Rat pups were suckled in
      litters of 4, 10, or 16 to induce differences in food intake. At 21 days of age,
      muscle protein and DNA were quantitated and biochemical maturation was assessed
      from measurement of [3H]ouabain-binding site abundance and myosin isoform
      composition. Differences in food intake produced a twofold range in body and
      muscle weights and protein and DNA contents. Protein accretion was more sensitive
      to nutrient intake in the soleus than in the EDL. Serum 3-5,3'-triiodothyronine
      (T3) and insulin concentrations decreased with a reduction in food intake. Total
      ouabain-binding sites were not altered in either muscle and were independent of
      muscle size. Differences in myosin isoform composition were more pronounced for
      the soleus than the EDL, but were relatively small in magnitude. These results
      demonstrate that, whereas postnatal muscle protein accretion and circulating
      hormone concentrations are sensitive to food intake, the biochemical maturation
      is resilient. The immature muscle does not exhibit the fiber type-specific
      responses to malnutrition typical of mature muscle.

PMID- 9176339
TI  - Vasopressin modulation of medullary blood flow and pressure-natriuresis-diuresis
      in the decerebrated rat.
AB  - Studies in our laboratory and others have demonstrated that arginine vasopressin
      (AVP) exerts potent vasoconstrictor actions on the vessels supplying the renal
      medulla. The physiological importance of these vascular effects of AVP has been
      difficult to assess because of high endogenous levels of AVP in anesthetized,
      surgically prepared animals. We have developed a decerebrated, hypophysectomized,
      renal-denervated rat model that enables us to study the effects of low levels of
      AVP on the pressure-diuresis, relationship under acute conditions. These rats
      maintain normal mean arterial pressure (MAP) and plasma AVP (2.5 pg/ml). Cortical
      and medullary blood flow (CBF and MBF, respectively) were measured by laser
      Doppler flowmetry and total renal blood flow (RBF) by transit time flowmetry.
      Renal interstitial fluid pressure (RIFP) and urinary sodium excretion (UNaV)
      responses were determined during controlled increases of MAP produced by aortic
      occlusion below the renal arteries. From a baseline of 97 +/- 2 mmHg, 30%
      increases in MAP resulted in a 63% increase in MBF, 35% increase in RIFP, and
      sixfold increase in UNaV, whereas CBF and RBF remained unchanged. Infusion of AVP
      (0.50 ng.kg-1.min-1, which increased plasma AVP from normal control levels of 3
      pg/ml to 11 pg/ml) produced no change in baseline MAP, RBF, or CBF but lowered
      MBF by 24%, RIFP by 26%, and UNaV by 71%. The slope of the relationship of AP and
      UNaV, MBF, and RIP was reduced to nearly zero by these small increases of plasma
      AVP. We conclude that an increase of plasma AVP in the range that occurs with
      water restriction decreases MBF selectively and greatly attenuates the arterial
      pressure-MBF and pressure-natriuretic relationship.

PMID- 9176340
TI  - Freezing-induced genes in wood frog (Rana sylvatica): fibrinogen upregulation by
      freezing and dehydration.
AB  - Differential screening of a cDNA library produced from liver of the freeze
      tolerant wood frog, Rana sylvatica, was used to search for freezing-induced
      genes. Five freezing-responsive cDNA clones representing different genes were
      isolated when approximately 80,000 plaques of a cDNA library, prepared from liver
      of frozen frogs (24 h at -2.5 degrees C), were screened with 32P-labeled total
      cDNA probes from control (5 degrees C) versus freezing-exposed frogs. Two clones,
      pBfFR45 and pBfFR04, are reported here in detail and were found to be homologous
      with the genes for the alpha- and gamma-subunits of fibrinogen, respectively. The
      clone pBfFR45 carried a 2,305-hp cDNA sequence that was of bipartite structure,
      containing two open reading frames (ORFs). The first ORF potentially encoded a
      332-residue polypeptide, covering a partial sequence of the NH2-terminal region
      of the alpha-chain. The second ORF encoded a 247-amino acid sequence, covering
      the whole COOH-terminal region of the alpha-chain; this was highly homologous to
      the FASORF (fibrinogen-alpha second ORF) of chicken alpha-fibrinogen and the
      extended alpha-chain of the human protein. Under control (5 degrees C)
      conditions, moderate levels of fibrinogen alpha- and gamma-transcripts were
      exclusively found in liver. When frogs were given survivable freezing exposures,
      levels of these transcripts in liver were highly induced. Transcription of these
      genes was also elevated in gut and lung during freezing, but mRNA levels in these
      tissues were lower than in liver. A time course assay confirmed that the
      transcript levels of both alpha- and gamma-subunit genes were dramatically
      elevated within the early hours of freezing and reached a maximum threefold
      increase over control levels after 8 h of freezing exposure. Two other
      physiological stresses, whole body dehydration and anoxia exposure, mimic
      individual elements of freezing stress in wood frogs. Northern blot hybridization
      analysis showed that the expression of both the alpha- and gamma-genes was also
      upregulated in response to dehydration in vivo (20% of total body water lost),
      but both were completely inhibited by anoxia exposure.

PMID- 9176341
TI  - Central thromboxane receptors: mRNA expression and mediation of pressor
      responses.
AB  - These studies tested whether activation of central thromboxane
      (Tx)A2/prostaglandin (PG) H2 receptors raises blood pressure (BP). Messenger RNA
      for TxA2/PGH2 receptors was detected in normal Sprague-Dawley rat brain and in
      rat neuronal and astroglial brain cells in culture. The mean arterial blood
      pressure (MAP) was recorded in conscious rats during graded administration of the
      TxA2/PGH2 receptor agonist U-46,619 given intracerebroventricularly or
      intravenously. Because the pressor responses to intracerebroventricular (but not
      intravenous) U-46,619 were significantly greater in-high-salt compared with low
      salt rats, high-salt rats were used for subsequent studies. The rise in MAP with
      intracerebroventricular administration of U-46,619 was greater than with
      intravenous administration and was more sustained. A comparison of plasma
      radioactivity after intracerebroventricular or intravenous injection of [3H]U
      46,619 demonstrated that approximately 35% of the drug reached the systemic
      circulation by 5-15 min after intracerebroventricular administration.
      Coadministration of a TxA2/PGH2 antagonist, ifetroban, by intravenous or
      intracerebroventricular routes blocked the pressor responses induced by U-46,619.
      The half-maximal inhibition for blockade of responses was substantially lower for
      intracerebroventricular than for intravenous responses (intracerebroventricular:
      0.03 +/- 0.01 vs. intravenous: 3.1 +/- 0.6 micrograms/kg; P < 0.001). The
      intravenous administration of ifetroban (10 micrograms/kg) caused a greater (P <
      0.02) inhibition of pressor responses to U-46,619 (1 microgram/kg) given
      intravenously (81 +/- 3%) compared with U-46,619 given intracerebroventricularly
      (40 +/- 13%). In conclusion, TxA2/PGH2 receptor mRNA is expressed in neurons,
      glial, and brain stem of normal rats. The central administration of a TxA2/PGH2
      mimetic raises blood pressure by interaction with specific central and peripheral
      receptors. This response is augmented in rats fed a high-salt compared with a low
      salt diet.

PMID- 9176342
TI  - On the role of muscarinic and peptidergic receptors in ganglionic transmission in
      bullfrogs in vivo.
AB  - Synaptic activity of individual B and C cells in the paravertebral sympathetic
      ganglia of urethan-anesthetized bullfrogs was monitored with intracellular
      electrodes. Postganglionic activity from the B and C fiber populations was
      monitored with suction electrodes. Intravenous infusion of muscarine (0.1 ml of 8
      microM) excited individual B cells and increased the amplitude and rate of
      spontaneous, postganglionic B fiber population discharges. Muscarine also
      increased the number of action potentials (APs) within each burst of synaptic
      activity in individual C cells. Because atropine (0.1 ml of 0.1 microM) had
      little or no effect on postganglionic population B or C fiber activity, the
      muscarinic slow inhibitory postsynaptic potentials and slow excitatory
      postsynaptic potentials (EPSPs) are unlikely to be involved in the transmission,
      modulation, or integration of postganglionic outflow in vivo. Atropine did,
      however, decrease the number of APs per burst in individual C cells, an effect
      that could be explained if excitatory presynaptic muscarinic receptors exist on C
      fiber terminals. Stimulation of preganglionic C fibers at "physiological"
      frequencies evoked a lasting afterdischarge in postganglionic B fibers that was
      blocked by a combination of atropine and [D-pyro-Glu1,D-Phe2,D-Trp3,6]
      luteinizing hormone-releasing hormone (LHRH). Release of LHRH from C fiber
      terminals and activation of the peptidergic, late-slow EPSP mechanism in B cells
      may therefore play a role in ganglionic transmission in vivo.

PMID- 9176343
TI  - Effect of intravenous angiotensin II on Fos distribution and drinking behavior in
      rabbits.
AB  - We investigated the effect of intravenous infusion of angiotensin II (ANG II, 40
      ng.kg-1.min-1) on the distribution of Fos in the subfornical organ (SFO), organum
      vasculosum of the lamina terminalis (OVLT), and the medulla of the conscious
      rabbit. ANG II elicited significant increases in the number of Fos-positive cell
      nuclei in the SFO and OVLT (15- and 10-fold, respectively). Raising blood
      pressure with phenylephrine did not elicit Fos in these nuclei. These nuclei are
      believed to be responsible for the dipsogenic actions of ANG II; however, ANG II
      was not dipsogenic. When blood pressure was held at preinfusion levels by the
      coadministration of sodium nitroprus-side and ANG II, the rabbits did not drink
      but Fos production in the lamina terminalis was elevated. In the medulla, ANG II
      did not significantly increase Fos production in the nucleus of the solitary
      tract (NTS) or ventrolateral medulla (VLM). However, with the coadministration of
      sodium nitroprusside, there were marked increases in the NTS and VLM. The results
      suggest that neurons in the SFO and OVLT are either not involved in the
      dipsogenic pathways or there is disruption further downstream in the central
      pathways that would normally mediate a drinking response to ANG II.

PMID- 9176344
TI  - Ventromedial hypothalamic lesions impair glucoregulation in response to
      endotoxin.
AB  - The purpose of the present study was to determine the role of the ventromedial
      hypothalamus (VMH) in regulating counter-regulatory hormone release and the
      increase in glucose flux that is observed after injection of endotoxin
      [lipopolysaccharide (LPS)]. Bilateral lesions of the VMH were produced
      electrolytically 2 wk before the experiment; sham-operated rats served as
      controls. [3-3H]glucose was infused to assess whole body glucose flux before and
      for 4 h after intravenous injection of Escherichia coli LPS. In control rats, LPS
      increased the plasma concentrations of glucose and lactate and the rates of
      glucose appearance and disappearance. In these animals, LPS also produced
      sustained elevations in corticosterone, glucagon, and catecholamines. In
      contrast, the glucose metabolic response to LPS was attenuated by > 50% in VMH
      lesioned rats. These changes were associated with a blunted increase in the
      plasma concentration of glucagon, epinephrine, and norepinephrine in VMH-lesioned
      rats compared with control animals. There was no difference in the plasma
      concentrations of corticosterone or TNF-alpha between the two groups after LPS or
      the responsiveness of sham- and VMH-lesioned rats to an infusion of either
      glucagon or epinephrine. These data indicate that the VMH plays a central role in
      regulating the secretion of glucagon and catecholamines and the stimulation of
      glucose flux after LPS.

PMID- 9176345
TI  - Growth of artificially fed infant rats: effect of supplementation with insulin
      like growth factor I.
AB  - Insulin-like growth factor I (IGF-I), a potent mitogenic peptide, is present in
      considerable quantities in most mammalian milks, but its importance for the
      neonate is unknown. To test the hypothesis that milk-borne IGF-I is an important
      factor in the regulation of neonatal growth, as well as that of the
      gastrointestinal tract, rat pups were fed a rat milk substitute (RMS) devoid of
      growth factors via gastrostomy. These animals were compared with those given RMS
      supplemented with recombinant human IGF-I added at a concentration of 500 ng/ml.
      Animals given RMS + IGF-I gained mere weight than controls, although skeletal
      growth as represented by elongation of the tail was no different. Animals fed RMS
      + IGF-I had increased brain and liver wet weights as well as increased liver and
      small intestine protein contents. Serum IGF-I concentrations in the IGF-I
      supplemented group were more than twofold above RMS controls and were similar to
      dam-fed rat pups. Semiquantification of serum IGF-binding proteins (IGFBP) in
      these animals documented that in IGF-I-supplemented pups the amount of 38- to 40
      kDa molecular mass IGFBP species was also greater than in RMS controls. The rate
      of migration of enterocytes from crypts in duodenum and proximal jejunum was
      greater in IGF-I-supplemented animals than in rats fed RMS alone. These studies
      suggest that milk-borne IGF-I is important in modulation of somatic and
      gastrointestinal tract growth in the neonatal rat.

PMID- 9176346
TI  - The kidneys stimulate vasopressin release during hemorrhage in rats with chronic
      NTS lesions.
AB  - Elimination of baroreceptor afferent input to the brain produced by chronic
      lesion of nucleus of the solitary tract (NTS) does not alter vasopressin (VP)
      release during hypotensive hemorrhage in conscious rats. To investigate whether
      the kidneys play a critical role in stimulating VP release during hemorrhage in
      chronic NTS-lesioned rats, we examined the effects of removing potential signals
      arising from the kidneys. In NTS-lesioned rats, nephrectomy or renal denervation,
      but not captopril injection, markedly attenuated (but did not abolish) hemorrhage
      induced VP release. In contrast, none of these manipulations attenuated the VP
      response in NTS-intact rats. Hemorrhage increased plasma renin activity in
      control and NTS-lesioned rats, and this response was not altered by renal
      denervation. In rats with NTS lesions and renal denervation, hemorrhage induced
      the expression of Fos in hypothalamic magnocellular VP neurons in a pattern
      similar to that of hemorrhage in intact rats. Collectively, these results
      indicate that in chronic NTS-lesioned rats an afferent signal arising from the
      kidneys stimulates VP release during hemorrhage, possibly through renal nerves.
      However, with the NTS intact or after the selective removal of arterial
      baroreceptor inputs, such a role for the kidneys is not apparent. Furthermore, in
      the absence of the NTS and renal nerves, another signal generated by hypotensive
      hemorrhage continues to stimulate VP neurons.

PMID- 9176347
TI  - beta-MHC transgene expression in suspended and mechanically overloaded/suspended
      soleus muscle of transgenic mice.
AB  - Non-weight-bearing (NWB) activity [space flight and hindlimb suspension (HS)]
      results in the loss of soleus muscle mass, a slow-to-fast fiber-type conversion,
      and decreased beta-myosin heavy chain (beta-MHC) protein and mRNA expression. To
      identify beta-MHC promoter sequences required for decreased beta-MHC expression
      in response to HS, we have modified an existing noninvasive hindlimb unweighting
      model to accommodate the use of (transgenic) mice. After 2 wk of HS, body and
      muscle (soleus > gastrocnemius > plantaris) weights were decreased as was the
      proportion of histochemically classified type I fibers in HS soleus muscle.
      Northern blot analysis revealed decreases in endogenous mRNA representing beta
      MHC, slow myosin light chain 1 and 2, and cardiac/slow troponin C, whereas those
      representing skeletal troponin C, muscle creatine kinase, and glyceraldehyde-3
      phosphate dehydrogenase increased. Protein extracts prepared from HS soleus (SS)
      muscle of mice harboring transgenes comprised of 5.6 or 0.6 kilobase of wild type
      (wt) mouse beta-MHC promoter (beta 5.6 wt, beta 0.6wt) and those carrying the
      simultaneous mutation (mut) of the MCAT, C-rich, and beta e3 subregions (beta
      5.6mut3, beta 0.6mut3) revealed decreases in chloramphenicol acetyltransferase
      (CAT) specific activity relative to respective controls. Decreased CAT mRNA was
      observed for transgene beta 5.6mut3, line 85. Two weeks of the simultaneous
      imposition of mechanical overload (synergist ablation) and HS (MOV/HS)
      countermanded the loss in absolute and normalized SS weight but did not decrease
      beta 0.6wt transgene expression. These transgenic results demonstrate that
      regulatory sequences within a 600-base pair beta-MHC promoter are sufficient to
      direct decreased transcription of beta-MHC transgenes after 2 wk of HS.

PMID- 9176348
TI  - Role of endotoxin in the response to experimentally induced bacteremia in
      chronically prepared rats.
AB  - Chronically prepared rats were injected intravenously with live Escherichia coli
      in doses from approximately 10(5) to approximately 10(9) colony-forming units
      (CFU). Significant dose-related increase in plasma adrenocorticotropin and
      corticosterone occurred after approximately 10(7) CFU. Fever occurred after
      approximately 10(7) CFU but not after approximately 10(9) CFU. These responses
      changed significantly but were not blocked completely when > 94% of the viable E.
      coli was removed from the inoculates. The remaining endotoxin activity in the
      inoculates resembled lipopolysaccharide (LPS) extracted from the same strain of
      E. coli on electrophoretic gels. Plasma endotoxin increased for > or = 240 min to
      5.1 +/- 0.9 endotoxin units (EU)/ml after approximately 10(7) CFU and to 440 +/-
      59 EU/ml after approximately 10(9) CFU. Endotoxin at approximately 10(9) CFU
      caused death within 24 h that was not predicted by the total activity of
      endotoxin that was injected. In contrast, extracted LPS with its strain and total
      activity matched to approximately 10(7) CFU mimicked the responses to this
      nonfatal dose. The total endotoxin activity of the injected bacteria appears to
      account for the effects of nonfatal doses of E. coli but not for the effects of
      fatal doses.

PMID- 9176349
TI  - Female rats do not develop sucrose-induced insulin resistance.
AB  - In male rats, 2 wk of high-sucrose feeding results in insulin resistance and
      hypertriglyceridemia [Pagliassotti, M.J., P.A. Prach, T.A. Koppenhafer, and D.A.
      Pan. Am. J. Physiol. 271 (Regulatory Integrative Comp. Physiol. 40): R1319-R1326,
      1996]. The present study aimed to determine if female rats also become insulin
      resistant and hypertriglyceridemic in response to high-sucrose feeding. Female
      Wistar rats (7 wk old) were fed either a high-sucrose diet (68% energy) (SU) or a
      high-starch diet (68% energy) (ST) for 3, 5, or 8 wk. In each animal, glucose
      kinetics were measured using [3-(3)H]glucose under basal and hyperinsulinemic
      conditions (insulin infusion 4.0 mU.kg-1.min-1). Body weight and basal glucose
      kinetics were not different between diet groups at 3, 5, or 8 wk. Glucose
      infusion rate (mg.kg-1.min-1) was not different between groups (3 wk: 17.7 +/-
      1.6 ST, 16.6 +/- 0.9 SU; 5 wk: 16.1 +/- 0.9 ST, 15.1 +/- 2.0 SU; 8 wk: 18.3 +/-
      1.9 ST, 16.1 +/- 1.5 SU). Clamp rate of glucose appearance (mg.kg-1.min-1) was
      also not different between diet groups (3 wk: 4.0 +/- 1.6 ST, 3.6 +/- 1.4 SU; 5
      wk: 2.6 +/- 1.0 ST, 2.3 +/- 1.14 SU; 8 wk: 5.9 +/- 1.8 ST, 7.7 +/- 1.2 SU). No
      difference was observed in plasma and tissue triglycerides or tissue glycogen
      between sucrose- and starch-fed animals. We therefore conclude that female rats,
      in contrast to males, do not develop sucrose-induced insulin resistance and
      hypertriglyceridemia.

PMID- 9176350
TI  - Lactate transport by rainbow trout white muscle: kinetic characteristics and
      sensitivity to inhibitors.
AB  - This study used an isolated-perfused tail-trunk preparation of rainbow trout to
      examine the uptake and release of lactate (Lac) and metabolic protons (delta H+M)
      in resting and exercised fish white muscle. In exercised muscle, L(+)-Lac efflux
      was inhibited (approximately 40%) by 5 mM alpha-cyano-4-hydroxycinnamate (CIN),
      but not by 0.5 mM 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS)
      or 0.1 mM amiloride. These results suggest that Lac release occurs through a Lac(
      )-H- symport and the free diffusion of lactic acid (HLac) or Lac-, but not via
      the Lac-/HCO3(-)-Cl- antiporter. Lac efflux was accompanied by delta H+m influx
      in all treatments, and increased delta H+m influx occurred after SITS treatment.
      In resting muscle, Lac uptake rates were greater than Lac efflux rates in the
      postexercise preparation. L-Lac influx exhibited partial saturation kinetics,
      whereas D(-)-Lac influx was linearly related to its extracellular concentration
      (0-32 mM). At 16 mM extracellular L-Lac, with a negligible transmembrane L-HLac
      gradient and an outwardly directed not driving force on L-Lac-, CIN, and SITS
      reduced net L-Lac uptake by 75 and 45%, respectively. At 16 mM extracellular
      concentration, D-Lac influx was 64% of the net L-Lac influx. These results
      suggest that in trout muscle at 16 mM extracellular L-Lac, the Lac -H+ symport
      accounts for 30-36%, the Lac-/HCO3(-)-Cl- antiport for 39-45%, and diffusion for
      19-25% of uptake, although the latter is probably overestimated and the former
      underestimated for methodological reasons. Net L-Lac efflux was not affected by
      extracellular D-Lac concentration and/or D-Lac influx, implying the existence of
      a concurrent L-Lac efflux during L-Lac influx. The D-Lac influx kinetics data
      indicated that the Lac-/HCO3 antiport was not saturable in the extracellular D
      Lac concentration range of 0-32 mM. This study clearly demonstrates the
      involvement of carrier-mediated transport in transmembrane Lac movement in fish
      muscle and supports the "active lactate retention" mechanism proposed by Turner
      and Wood (J. Exp. Biol. 105: 895-401, 1983).

PMID- 9176351
TI  - Cardiovascular response to stress: baroreflex resetting and hemodynamics.
AB  - Borderline hypertensive rats (BHR) were used to test the hypothesis that
      baroreflex resetting prevents a fall in blood pressure (BP) when cardiac output
      (CO) is reduced during air-jet stress. Eight-week-old BHR were instrumented with
      flow probes around the ascending aorta for measuring CO, femoral and jugular
      catheters were inserted for measurement of arterial pressure and infusion of
      drugs, and sinoaortic baroreceptors were either denervated (SAD) or left intact.
      Alternating bolus injections of phenylephrine and sodium nitroprusside were given
      at baseline and during air-jet stress to assess the baroreflex. Air-jet stress
      immediately shifted the midpoint of the baroreflex curve for heart rate (HR) to a
      higher BP levels. When metoprolol was administered during air-jet stress, HR was
      reduced and CO reverted to prestress levels, but the stress-induced pressor
      response was not changed. In SAD BHR, air-jet stress caused an elevation of BP
      that was not different from intact rats. Administration of metoprolol to SAD rats
      during air-jet stress resulted in a further elevation rather than a reduction in
      BP. We conclude that the sinoaortic cardiac baroreflex is reset during air-jet
      stress and that it integrates reflex changes in BP during stress. The arterial
      baroreflex is not, however, necessary for the initiation or maintenance of the
      pressor response during stress, nor does it prevent a fall in BP when CO is
      compromised during stress.

PMID- 9176352
TI  - Lymph flow in sheep with rapid cardiac ventricular pacing.
AB  - Increases in systemic venous pressure (Pv) associated with heart failure cause an
      increase in microvascular fluid filtration into the tissue spaces. By removing
      this excess filtrate from the tissues, lymphatic vessels help to prevent edema.
      However, the lymphatics drain into systemic veins and an increase in Pv may
      interfere with lymphatic flow. To test this, we cannulated caudal mediastinal
      node efferent lymphatics in sheep. We used rapid cardiac ventricular pacing (240
      275 beats/min) to cause heart failure for 4-7 days. Each day we determined the
      lymph flow rate two ways. First, we adjusted the lymph cannula height so that the
      pressure at the outflow end of the lymphatic was zero. After we determined the
      lymph flow with zero outflow pressure, we raised the cannula so that outflow
      pressure was equal to the actual venous pressure. We quantitated the effect of
      venous pressure on lymph flow rate by comparing the flow rate with outflow
      pressure = Pv to the flow rate with zero out low pressure. At baseline, Pv = 5.0
      +/- 2.5 (SD) cmH2O and we found no difference in the two lymph flow rates. Pacing
      caused Pv and both lymph flow rates to increase significantly. However for Pv <
      15 cmH2O, we found little difference in the two lymph flow rates. Thus increases
      in Pv to 15 cmH2O at the outflow to the lymphatics had little effect on lymph
      flow. By comparison, Pv > 15 cmH2O slowed lymph flow by 55 +/- 29% relative to
      the lymph flow rate with zero outflow pressure. Thus Pv values > 15 cmH2O
      interfere with lymph flow from the sheep caudal mediastinal lymph node.

PMID- 9176353
TI  - Reduction of intake in the rat due to gastric filling.
AB  - With two exceptions, the literature shows that confining ingested fluid to the
      stomach of a rat during an intake test had no effect on the volume ingested. In
      the two exceptions (J. D. Davis and J. L. Sayler, Physiol. Behav. In press. J. A.
      Deutsch, Handbook of Behavioral Neurobiology. Neurobiology of Food and Fluid
      Intake, edited by E. M. Stricker. New York: Plenum, 1990, vol. 10), intake with
      the cuff open was very large, suggesting that, when intake on cuff-open tests
      exceeds some critical volume, confining all of it to the stomach during the test
      will reduce intake. To test this, we measured intake of three different solutions
      known to stimulate large intake with the pylorus open and closed. In cuff-closed
      tests, intake was less than in cuff-open tests. In cuff-closed tests, rate of
      licking began to decline within 5-6 min when only about one-quarter of the
      ultimate contents of the stomach had accumulated, indicating that some signal
      from the stomach slowed the rate of ingestion before the full capacity of the
      stomach was reached. This shows that the stomach is sensitive to its contents
      when it contains only a small proportion of its capacity.

PMID- 9176354
TI  - Canine adrenal catecholamine response to VIP is blocked by PACAP-(6-27) in vivo.
AB  - The goal of the present study was to characterize the adrenal catecholamine
      response to exogenous vasoactive intestinal peptide (VIP) in anesthetized dogs.
      We studied the potential involvement of mechanism(s) mediated by muscarinic
      receptors, L-type Ca2+ channels, VIP-ergic receptors, or pituitary adenylate
      cyclase-activating peptide (PACAP) receptors. The study consisted of five groups:
      a vehicle control group receiving VIP (5 micrograms) in the presence of saline
      and four drug-treated groups receiving VIP (5 micrograms) in the presence of
      either atropine (500 micrograms), nifedipine (50 micrograms),
      [Lys1,Pro2,5,Arg3,4,Tyr6]VIP (50 micrograms), or PACAP-(6-27) (50 micrograms).
      All drugs were locally infused to the left adrenal gland. Plasma catecholamine
      concentrations were measured in adrenal venous and aortic blood by a high
      pressure liquid chromatography-electrochemical method. In the control group, VIP
      produced a significant increase in adrenal catecholamine output. Neither
      atropine, nifedipine, nor[Lys1,Pro2,5,Arg3,4,Tyr6]-VIP significantly affected the
      medullary response to VIP. In the presence of PACAP-(6-27), however, the
      catecholamine response to VIP was attenuated by approximately 77% (P < 0.05). The
      present study suggests that adrenal catecholamine secretion induced by exogenous
      VIP may be mediated by a PACAP-related mechanism, most probably through a PACAP
      type I receptor, in anesthetized dogs. The data also indicate that neither
      muscarinic receptors, VIP-ergic receptors, nor dihydropyridine-sensitive L-type
      Ca2+ channels are operative in the adrenal catecholamine response to exogenous
      VIP in vivo.

PMID- 9176355
TI  - Lymphatic drainage of the CNS: effects of lymphatic diversion/ligation on CSF
      protein transport to plasma.
AB  - The plasma recovery of an intraventricularly administered protein was compared
      before and after lymph diversion/ligation in the same conscious sheep to
      determine the relative roles of arachnoid villi and lymphatics in the clearance
      of a cerebral spinal fluid tracer. 125I-human serum albumin was injected into
      both lateral ventricles, and venous blood was sampled. One day later, multiple
      cervical vessels and the thoracic duct were cannulated for lymph collection.
      Uncannulated vessels were ligated. The experiment was repeated with 131I-human
      serum albumin as the tracer. Before lymph diversion/ligation, the time-averaged
      tracer transport into the plasma was 6.4 +/- 1.0%/h, with an average 6-h plasma
      recovery of 38.2 +/- 5.7% (percentage of injected dose). After lymph
      diversion/ligation, the values dropped to 2.9 +/- 0.5%/h and 17.7 +/- 2.7%,
      respectively. The collected lymph contained 8.7 +/- 2.6% of the tracer. No
      significant differences were observed in sham-operated animals. In conclusion,
      extracranial lymphatic vessels in sheep transport approximately one-half of the
      protein tracer from the cerebral spinal fluid compartment into plasma.

PMID- 9176356
TI  - Muscle enzyme activity in humans: role of substrate availability and training.
AB  - To study the effect of nutrient intake (substrate flux) and training on muscle
      enzyme activities, 36 untrained healthy men adapted for 7 wk to a fat-rich or a
      carbohydrate-rich diet. Ten of the 18 subjects on each diet completed an
      endurance training program, and the remaining 8 served as controls. Maximal
      oxygen uptake was increased (11%) in the trained groups (P < 0.05). Irrespective
      of training, beta-hydroxyacyl-CoA-dehydrogenase activity in the vastus lateralis
      muscle was significantly increased by an average of 25% after adaptation to a fat
      rich diet and was unchanged after adaptation to a carbohydrate-rich diet. In
      contrast, irrespective of diet, muscle citrate synthase activity and hexokinase
      activity were increased (P < 0.05) after adaptation to training by 17 and 18% in
      the group fed the carbohydrate, rich diet and by 17 and 12% in the group fed the
      fat-rich diet, respectively, and were unchanged in the two control groups. We
      suggest that diet can affect muscle enzymatic adaptation, presumably through an
      effect on the substrate flux.

PMID- 9176357
TI  - Cholecystokinin activates area postrema neurons in rat brain slices.
AB  - Peripheral cholecystokinin (CCK) reduces food intake and triggers the secretion
      of both oxytocin and corticotropin-releasing hormone. These responses are
      partially initiated by activation of receptors in the peripheral endings of the
      vagus nerve. However, in vivo studies showing that after vagotomy systemic CCK
      induces fos activation of neurons in the area postrema (AP) suggest that
      circulating CCK may directly influence the activity of neurons in this structure.
      The present study was therefore designed to investigate the responsiveness of AP
      neurons to CCK using in vitro extracellular single-unit recording techniques.
      Bath application of 100 nM CCK for 200 s resulted in excitatory responses in 41%
      and inhibitory effects in 6% of 143 AP neurons tested. Application of multiple
      doses of CCK (1-100 nM) to single neurons demonstrated that CCK effects were dose
      dependent. The firing rate of tested neurons increased by 48 +/- 15% in response
      to 1 nM, by 89 +/- 22% in response to 10 nM, and by 242 +/- 77% in response to
      100 nM CCK. After we blockaded synaptic transmission with a low-Ca2+/high-Mg2+
      artificial cerebrospinal fluid, the excitatory effects of CCK remained in all
      nine neurons tested. The CCK-receptor antagonist L-364,718 had no significant
      effect on the responses to CCK (P > 0.1, n = 4), whereas, after perfusion of
      slices with the CCKB-receptor antagonist L-365,260, mean responses to CCK were
      significantly reduced to 12.6 +/- 4.7% of the control value (P < 0.001, n = 4).
      These results demonstrate a direct and dose-dependent excitatory action of CCK on
      AP neurons that is abolished by CCKB-receptor antagonists. These data emphasize
      the potential role of AP in processing afferent information derived from
      circulating peptide concentrations that could be involved in the regulation of
      food intake.

PMID- 9176358
TI  - Glutamate release in parabrachial nucleus and baroreflex alterations after vagal
      afferent activation.
AB  - The parabrachial nucleus (PBN) is a regulatory nucleus that relays visceral
      information from the brain stem to the cortex. Immunohistochemical studies have
      shown that the levels of various neuropeptides in the PBN were changed after
      visceral afferent activation. Because the major transmitter relaying visceral
      information through the PBN is glutamate, the present study asked if glutamate
      release into the PBN also was changed after vagal afferent activation in
      anesthetized male rats. The distally crushed vagus was stimulated (50 Hz, 1-2 mA,
      1 s on, 2 s off) for 2 h. Dialysates of the PBN were collected every 30 min and
      assayed for glutamate using high-performance liquid chromatography. Extracellular
      glutamate concentrations were reduced during the vagal stimulation, increased
      fourfold compared with prestimulated levels after the stimulation was terminated,
      and returned to prestimulated levels over the next 2 h poststimulation. These
      changes were not due to alterations in blood pressure because sodium
      nitroprusside infusion for the same interval resulted in a similar hypotension,
      but increased glutamate release. Phenylephrine and sodium nitroprusside were
      infused intravenously to measure the cardiac baroreflex before, during, and after
      vagal stimulation. The pressor (but not the depressor) response was elevated
      during the period of enhanced glutamate release, and the baroreflex curve was
      shifted to the right (increased threshold) without a change in gain. These
      changes in the cardiac baroreflex were reduced, but still seen, when the PBNs
      were dialyzed bilaterally with the glutamate antagonists MK-801 and 6-cyano-7
      nitroquinoxaline-2,3-dione. Thus visceral activation alters glutamate release in
      the PBN and has enduring effects on cardiac baroreflex function.

PMID- 9176359
TI  - Hepatic fatty acid metabolism in pigs and rats: major differences in endproducts,
      O2 uptake, and beta-oxidation.
AB  - Models of mammalian hepatic lipid metabolism are based largely on observations
      made in adult rats, emphasizing ketogenesis as a primary adjunct to mitochondrial
      beta-oxidation. Studies using piglets have illustrated the divergent nature of
      intermediary metabolism in this model, wherein ketogenesis and beta-oxidation are
      small and acetogenesis is an important route of fuel carbon flux. To clarify
      potential species differences in hepatic lipid metabolism and its control, we
      compared O2 consumption and metabolic end products in fasted pig and rat liver
      homogenates treated with 1-[14C]C16:0. Carboxyl carbon accumulation in acid
      soluble products (ASP) plus CO2 was threefold greater and O2 consumption was
      twofold greater in rats (P < 0.05). Unlike rats, pigs showed negligible carboxyl
      carbon accumulation in ketone bodies (3-7% of ASP), whereas acetate was a
      carboxyl carbon reservoir in both animals (17-31% of ASP in pigs). Malonate
      increased (approximately 2-fold) and antimycin/rotenone decreased (40-60%)
      radiolabel accumulation in acetate. These data concur with the hypotheses that
      comparatively low hepatic beta-oxidative flux in piglets is partially related to
      a smaller metabolic rate and that substantial acetogenesis occurs
      intramitochondrially in both pigs and rats.

PMID- 9176360
TI  - Reflex pathways controlling urethral striated and smooth muscle function in the
      male rat.
AB  - The organization of vesicourethral reflex mechanisms in the male rat was studied
      by monitoring intraurethral pressure and the external urethral sphincter (EUS)
      electromyogram. EUS striated and urethral smooth muscle activities were elicited
      by reflex isovolumetric bladder contractions evoked by bladder filling or
      electrical stimulation of nerves in the bladder wall. Evoked EUS bursting
      activity in normal rats was eliminated in chronic spinal rats and replaced by
      tonic activity. Reflex urethral smooth muscle activity mediated by an increase in
      urethral pressure after paralysis of the EUS with alpha-bungarotoxin occurred in
      normal and chronic spinal rats. The response was significantly larger in chronic
      spinal (21.3 +/- 3.0 cmH2O) than in normal rats (4.2 +/- 0.7 cmH2O). NG-nitro-L
      arginine methyl ester (a nitric oxide synthase inhibitor, 20 mg/kg i.v.)
      increased the smooth muscle response in normal (5.9 +/- 1.3 cmH2O) and chronic
      spinal rats (6.9 +/- 1.8 cmH2O). This increase in urethral pressure was not
      changed by sympathetic nerve transection or prazosin (0.2-0.3 mg/kg i.v.) but was
      abolished by hexamethonium and reduced 74-89% by atropine. These results indicate
      that coordinated EUS function (bursting activity) in the male rat is dependent on
      supraspinal pathways and that the urethral smooth muscle response during voiding
      is composed of a predominant cholinergic, atropine-sensitive contraction as well
      as a nitric oxide-mediated relaxation. Both are mediated by activation of
      parasympathetic pathways and are maintained or significantly larger after spinal
      cord injury, indicating that they are dependent on spinal reflex pathways.

PMID- 9176361
TI  - Chemical lesion of visceral afferents causes transient overconsumption of
      unfamiliar high-fat diets in rats.
AB  - Because it is commonly assumed that the major role of visceral afferents in food
      intake control is to terminate meals by carrying negative-feedback signals to the
      brain, we hypothesized that overconsumption should occur in rats with chemically
      lesioned visceral afferents if they were presented with an unfamiliar diet. Adult
      male Sprague-Dawley (SD) rats were treated with multiple doses of capsaicin or
      vehicle as a control. Five weeks later, a series of 3-h feeding tests after 24-h
      deprivation was carried out, first with chow and then with either a solid
      (vegetable shortening) or liquid (Ensure) unfamiliar high-fat diet. Both groups
      consumed similar amounts of their powdered chow maintenance diet, but capsaicin
      treated rats consumed at least 50% more of either high-fat diet than vehicle
      controls (P < 0.01) at the beginning of the first trial. During second and third
      trials with the now-familiar high-fat diet, intake was no longer significantly
      different between the two groups, suggesting rapid engagement of redundant
      control mechanisms. These results support a role of capsaicin-sensitive visceral
      afferents in providing negative feedback for early meal termination during the
      ingestion of unfamiliar diets.

PMID- 9176362
TI  - Differential ventral septal vasopressin release is associated with sexual
      dimorphism in PGE2 fever.
AB  - The vasopressinergic innervation of the ventral septal area (VSA) has been shown
      to be implicated in antipyresis. Because this system is less well developed in
      female rats, we hypothesized that female rats would display exaggerated febrile
      responses. We therefore examined the temperature responses of conscious and
      urethan-anesthetized rats of both sexes to centrally administered prostaglandin
      E2 (PGE2) and correlated these responses with the release and action of
      endogenous arginine vasopressin (AVP) in the VSA. Both conscious [25 ng/5
      microliters PGE2 intracerebroventricularly (i.c.v.)] and anesthetized (VSA
      microdialyzed, 50 ng/5 microliters PGE2 i.c.v.) female rats had higher fevers
      than did males. Infusion of an AVP V1a receptor antagonist {1 nmol
      [d(CH2)5Tyr(Me)]AVP} plus PGE2 gave rise to higher fevers in males but not in
      females. Measurements of AVP in microdialysates of the VSA showed that the
      release of endogenous AVP was increased in response to PGE2 in males only.
      Baseline AVP release in both sexes was similar. The results suggest that there is
      a sex-related difference in PGE2 fever, which may be accounted for by the
      differential AVP release in the VSA.

PMID- 9176363
TI  - Verapamil abolishes the preglomerular response to ANG II during intrarenal nitric
      oxide synthesis inhibition.
AB  - We have recently reported that intrarenal nitric oxide (NO) synthesis inhibition
      exaggerates the preglomerular vasoconstrictor response more than the
      postglomerular response to angiotensin II (ANG II) in dogs. Previous studies have
      suggested that preglomerular vasoconstriction may be more dependent on
      extracellular calcium than postglomerular vasoconstriction. The purpose of this
      study is to determine whether the enhanced preglomerular response to ANG II
      during intrarenal NO synthesis inhibition occurs through voltage-gated calcium
      channels. In three groups of anesthetized dogs with stop-flow kidneys, the renal
      hemodynamic response to intrarenal ANG II infusion (2.0 ng.kg-1.min-1) was
      determined. Renal artery pressure was servo-controlled at 80 +/- 1 mmHg, and
      glomerular filtration rate was zero. In vehicle-treated dogs, ANG II decreased
      renal blood flow (RBF) by 29% and increased glomerular hydrostatic pressure (Pg)
      by 2.7 +/- 1.9 mmHg. Postglomerular vascular resistance increased by 51%, whereas
      preglomerular resistance was unchanged in response to ANG II. In dogs pretreated
      with an intrarenal infusion of NG-nitro-L-arginine methyl ester (L-NAME; 5
      micrograms.kg-1.min-1) for 60 min, ANG II decreased RBF by 36% and decreased Pg
      4.4 +/- 2.9 mmHg. In contrast to the vehicle-treated group, preglomerular
      resistance increased by 261% and postglomerular resistance increased by 48% after
      ANG II infusion in the L-NAME-treated group. In dogs pretreated with an
      intrarenal infusion of L-NAME and verapamil (50 micrograms/min) for 60 min, the
      renal hemodynamic response to ANG II was similar to the response in the vehicle
      treated dogs. ANG II decreased RBF by 25% and decreased Pg by 5.3 +/- 1.2 mmHg.
      Postglomerular resistance increased by 51%, whereas preglomerular resistance was
      unchanged in response to ANG II infusion in dogs with intrarenal NO synthesis and
      voltage-gated calcium channel blockade. These data indicate that the
      preglomerular response to ANG II under conditions of reduced NO synthesis within
      the kidney is dependent on voltage-gated calcium channels.

PMID- 9176364
TI  - Electrical fields enhance growth of cancer spheroids by reactive oxygen species
      and intracellular Ca2+.
AB  - A single electrical field pulse (500 V/m) with a duration of 60 s increased tumor
      outgrowth over a postpulse period of 24 h. RNA staining with acridine orange
      showed a rise in RNA content in pulsed spheroids, indicating stimulation of cell
      cycle activity. The electropulse induced an intracellular Ca2+ concentration
      ([Ca2+]i) transient that started approximately 40 s after the onset of the
      electrical field. Neither the presence of extracellular Ni2+ (0.5 mM) nor the
      absence of extracellular Ca2+ impeded the [Ca2+]i rise. It was, however, totally
      blocked by thapsigargin (1 microM), indicating that the initial Ca2+ response is
      due to Ca2+ release from intracellular stores. The [Ca2+]i transient was
      paralleled by an increase in reactive oxygen species (ROS), as revealed using
      2',7'-dichlorofluorescein diacetate as an indicator. The radical scavengers N
      acetyl-L-cysteine (NAC)(20 mM) and dehydroascorbate (5 mM) inhibited both ROS
      production and the [Ca2+]i transient during electrical field treatment. The
      mitogenic activation was dependent on the rise in [Ca2+]i because inhibition of
      Ca2+ release during electrical field treatment by addition of either thapsigargin
      or NAC to the incubation medium abolished the observed effect. We conclude that a
      single, direct current electrical field pulse induces production of ROS, which in
      turn mediate Ca2+ release from intracellular stores and activate cell cycle
      activity in multicellular spheroids.

PMID- 9176365
TI  - Afferent renal inputs onto subfornical organ neurons responsive to angiotensin
      II.
AB  - Experiments were done in pentobarbital sodium-anesthetized rats to investigate
      the effect of electrical stimulation of afferent renal nerves (ARN) on the
      discharge rate of subfornical organ (SFO) neurons that responded to changes in
      plasma levels of angiotensin II (ANG II) and projected directly to the
      paraventricular nucleus of the hypothalamus (PVH). Extracellular recordings were
      made from 76 histologically verified single neurons in the SFO that were excited
      by intracarotid infusions of ANG II. Of these units, 54.8% (23 of 42) responded
      with excitation to ARN stimulation (mean onset latency, 125 +/- 35 ms). None of
      the SFO units excited by plasma ANG II were found to be inhibited by ARN
      stimulation. An additional 34 units in the SFO that were excited by plasma ANG II
      were also antidromically activated by stimulation of the PVH. Of these neurons,
      17.8% (6 of 34) were also excited by stimulation of ARN. The results indicate
      that inputs from ARN converge onto SFO neurons that alter their discharge rate
      during changes in plasma concentration of ANG II and project directly to the PVH.
      These data suggest that ARN may play an important role in body fluid balance and
      circulatory regulation by modulating the activity of SFO neurons that function in
      the detection of blood-borne signals resulting from the decrease in extracellular
      fluid volume and arterial pressure and that influence the activity of
      hypothalamic nuclei that contain neurosecretory neurons.

PMID- 9176366
TI  - Biosynthesis and homeostatic roles of nitric oxide in the normal kidney.
AB  - Nitric oxide (NO) is an important molecular mediator of numerous physiological
      processes in virtually every organ. In the kidney, NO plays prominent roles in
      the homeostatic regulation of glomerular, vascular, and tubular function.
      Differential expression and regulation of the NO synthase (NOS) gene family
      contribute to this diversity of action. This review explores recent advances in
      the molecular and cell biology of the NOS isoforms and relates these findings to
      functions of NO in the control of normal renal hemodynamics, the glomerular
      microcirculation, and renal salt excretion. Newly recognized molecular diversity
      of the NOS gene products, factors governing NOS isozyme gene expression and
      catalytic activity, and the intrarenal distribution of the NOS isoforms are
      examined. Physiological data regarding the complex roles of NO in the control of
      renal hemodynamics and the glomerular microcirculation are analyzed, and the
      effects of chronic NOS inhibition on glomerular function and structure are
      presented. The contributions of NO to renal salt excretion as well as functional
      and molecular biological evidence for adaptive changes in NOS isoform expression
      during variations in dietary salt balance are discussed. Current investigative
      challenges and goals for future research of renal NO biology are presented.

PMID- 9176367
TI  - Molecular sieving of small solutes by outer medullary descending vasa recta.
AB  - Molecular sieving of small solutes by outer medullary descending vasa recta
      (OMDVR). Descending vasa recta (DVR) plasma equilibrates with the medullary
      interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven
      by transmural osmotic pressure gradients due to small hydrophilic solutes (delta
      pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway
      most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the
      ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when
      Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x
      10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na
      (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv.
      During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/-
      0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/-
      0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa and Rraf most
      accurately when the OMDVR reflection coefficient to the tracers is assigned a
      value near unity. This indicates that the OMDVR wall contains a pathway for
      osmotic volume flux that excludes small hydrophilic solutes, a behavior
      consistent with that of aquaporins.

PMID- 9176368
TI  - Evidence that aquaporin-1 mediates NaCl-induced water flux across descending vasa
      recta.
AB  - Outer medullary descending vasa recta (OMDVR) were perfused in vitro, and volume
      efflux was measured by driving water movement with transmural gradients of NaCl
      or albumin. Consistent with mediation by water channels, p
      chloromercuribenzenesulfonic acid (pCMBS) markedly inhibited volume flux induced
      by NaCl. Dithiothreitol reversed the inhibition, pCMBS did not significantly
      alter water flux induced by albumin. Osmotic water permeability (Pf) of the pCMBS
      sensitive pathway of glutaraldehyde-fixed and nonfixed OMDVR was 1,102 +/- 449
      and 1,257 +/- 718 microns/s (means +/- SD), respectively. pCMBS reduced Pf to
      near zero, whereas diffusional water permeability in the same vessels was only
      slightly inhibited. Immunoreactive aquaporin-1 (AQP1) measured by enzyme-linked
      immunosorbent assay in collagenase-treated and untreated OMDVR was 5.2 +/- 1.0
      and 4.2 +/- 0.4 fmol/mm, respectively, values that account well for the
      experimental Pf. We conclude that OMDVR water flux driven by NaCl gradients is
      most likely mediated by the AQP1 water channel and that NaCl and urea gradients
      drive water efflux in vivo by this route.

PMID- 9176370
TI  - Polycystin expression is temporally and spatially regulated during renal
      development.
AB  - Mutations in PKD1 cause autosomal dominant polycystic kidney disease (ADPKD), a
      common genetic disease in which cysts form from kidney tubules. The predicted
      product of this gene is a novel protein with cell-adhesive and membrane-spanning
      domains. To test the hypothesis that polycystin, the product of the PKD1 gene, is
      a cell adhesion molecule, we raised antibodies against peptides derived from the
      unduplicated, membrane-spanning portion of the predicted amino acid sequence.
      These antibodies recognized membrane-associated polypeptides of 485 and 245 kDa
      in human fetal kidney homogenates. Expression was greater in fetal than adult
      kidney by both Western blot analysis and immunofluorescence. In fetal kidney,
      polycystin was localized to the plasma membranes of ureteric bud and comma and S
      shaped bodies. However, in more mature tubules in fetal kidney, in adult kidney,
      and in polycystic kidney, the majority of polycystin staining was intracellular.
      The temporal and spatial regulation of polycystin expression during renal
      development lead us to speculate that polycystin may play a role in
      nephrogenesis.

PMID- 9176369
TI  - Agmatine affects glomerular filtration via a nitric oxide synthase-dependent
      mechanism.
AB  - Arginine decarboxylase is present in the kidney and metabolizes the amino acid,
      arginine, to agmatine. Agmatine increases filtration rate in single nephrons (J.
      J. Lortie, W. F. Novotny, O. W. Peterson, V. Vallon, K. Malvey, M. Mendonca, J.
      Satriano, P. Insel, S. C. Thomson, and R. C. Blantz. J. Clin. Invest. 97:413-420,
      1996). Experiments were conducted to determine whether exogenously administered
      agmatine exerts these effects via interaction with nitric oxide synthase (NOS)
      and whether this interaction depends upon alpha 2-adrenergic receptors. Agmatine
      microperfused (1 microM) into the urinary space of surface glomeruli of the rat
      increased nephron filtration rate from 33 +/- 4 to 40 +/- 5 nl/min with complete
      recovery within 10 min. When NG-monomethyl-L-arginine (L-NMMA), a nonselective
      NOS inhibitor, was systemically infused, agmatine no longer increased single
      nephron glomerular filtration rate (SNGFR). BHT-933, an alpha 2-adrenergic
      agonist, did not increase SNGFR and was unaffected by concurrent L-NMMA. In vitro
      incubation of freshly harvested glomeruli with agmatine resulted in significant
      increases in the generation of cGMP, effects similar to carbachol, and blocked by
      nitro-L-arginine methyl ester (L-NAME) but not yohimbine, an alpha 2-adrenergic
      antagonist. Agmatine exerts effects on glomerular ultrafiltration via a
      constitutive NOS-dependent mechanism, and this does not require the participation
      of alpha 2-adrenoreceptors.

PMID- 9176371
TI  - Osmolarity in renal medulla of transgenic mice regulates transcription via 5'
      flanking region of canine BGT1 gene.
AB  - Betaine is a major compatible osmolyte accumulated in the mammalian kidney
      medulla and in Madin-Darby canine kidney cells in response to hypertonicity. The
      accumulation is the result of an increase in maximal velocity of the Na(+)- and
      Cl-coupled betaine transporter designated BGT1. We have previously cloned the
      canine BGT1 gene and identified a tonicity-responsive enhancer element (TonE) in
      its 5'-flanking region. Here we report studies of transgenic mice that have in
      their genome 2.4 kb of the 5'-flanking region of the canine BGT1 gene in front of
      a chloramphenicol acetyl-transferase (CAT) reporter. Expression of CAT mRNA was
      detected only in the renal medulla and was increased by experimental
      manipulations that increase the tonicity of the renal medulla and decreased by
      manipulations that decrease medullary tonicity. We conclude that the 2.4-kb 5'
      flanking region of the BGT1 gene mediates an increase in transcription in
      response to hyperosmolarity in the renal medulla.

PMID- 9176372
TI  - Differential regulation of CHIF mRNA by potassium intake and aldosterone.
AB  - The channel-inducing factor (CHIF) is an epithelial-specific transmembrane
      protein, which is induced by aldosterone in distal colon (but not in kidney) and
      can evoke K+ conductance in Xenopus oocytes. The current study examined the
      possibility that CHIF participates in maintaining K+ balance by assessing its
      regulation during variations in K+ intake. In adrenal-intact rats, high-K+ diet
      stimulated, whereas K+ deficiency downregulated, CHIF mRNA both in kidney and
      colon. The downregulation of CHIF observed in rats fed a low-K+ diet for
      different periods of time closely correlated with a decrease in plasma K+ but
      also with changes in aldosterone levels. To differentiate between the two,
      modulation of CHIF has been studied in adrenalectomized rats with and without
      corticosteroid supplementation. These experiments have demonstrated that a low-K+
      intake suppresses CHIF mRNA, irrespective of aldosterone level. On the other
      hand, the upregulation evoked by a high-K+ load is apparent only in adrenal
      intact rats. This is despite the fact that infusing rats with aldosterone and
      corticosterone does not increase the expression of this mRNA in kidney. These
      findings may suggest a role for CHIF in preserving K+ balance.

PMID- 9176374
TI  - Apical and basal uptake of L-dopa and L-5-HTP and their corresponding amines,
      dopamine and 5-HT, in OK cells.
AB  - The present study defined the kinetic characteristics of L-3,4
      dihydroxyphenylalanine (L-dopa) and L-5-hydroxytryptophan (L-5-HTP) transport and
      their decarboxylation products, dopamine and 5-hydroxytryptamine (5-HT),
      respectively, in OK cells. The apical uptake of both L-dopa and 5-HTP was
      temperature dependent and stereoselective. Nonlinear analysis of the saturation
      curves revealed for L-dopa and L-5-HTP Michaelis constants of 13.8 and 29.1
      microM, respectively, and maximal velocities of 21 and 29 nmol.mg protein-1.6 min
      1, respectively, L-5-HTP inhibited the apical uptake of L-dopa with a half
      maximal inhibitory constant of 29.1 microM. The accumulation of L-dopa and L-5
      HTP from the basolateral cell border was dependent on the concentration used and
      saturable at nearly 50 microM. The accumulation of dopamine and 5-HT was found to
      be saturable only when the substrates were applied from the basolateral cell
      border. These results demonstrate that the L-dopa and L-5-HTP transporters in OK
      cells are located in both the apical and basolateral cell borders, whereas the
      uptake of dopamine and 5-HT is a saturable process only when the substrates are
      applied from the basolateral cell border.

PMID- 9176373
TI  - PKC isoforms in rat medullary thick ascending limb: selective activation of the
      delta-isoform by PGE2.
AB  - In the medullary thick ascending limb (MTAL) of the rat kidney, prostaglandin E2
      (PGE2) reverses inhibition of HCO3 absorption by arginine vasopressin (AVP). This
      effect of PGE2 is blocked by chelerythrine or staurosporine and mimicked by
      phorbol ester, suggesting a critical role for protein kinase C (PKC). The present
      study was designed to examine directly regulation of PKC isoforms by PGE2 in the
      inner stripe of the outer medulla and in microdissected MTALs. Immunoblots with
      isoform-specific anti-PKC antibodies detected alpha-, beta II-, delta-, epsilon-,
      and zeta-isoforms in both inner stripe and MTAL. The beta I- and gamma-isoforms
      were not detected. Translocation and activation of PKC were assessed by
      immunoblot analysis and by direct measurement of enzyme activity using an immune
      complex kinase assay. In inner stripe tissue incubated with 10(10) M AVP, PGE2
      10(6) M for 20 min) induced translocation of PKC-delta from the cytosolic
      fraction to the membrane fraction. This translocation was associated with an 85%
      increase in PKC-delta activity in the membrane fraction and a 70% decrease in PKC
      delta activity in the cytosolic fraction. PGE2 had no effect on the subcellular
      distribution or the activities of the other isoforms. Activation of PKC-delta was
      confirmed directly in microdissected MTALs, in which PGF2 caused a near complete
      loss of PKC-delta from the cytosolic fraction. PGE2 did not induce translocation
      of PKC-delta in the absence of AVP. These results demonstrate that 1) the MTAL
      expresses Ca(2+)-dependent (alpha, beta II) and Ca(2+)-independent (delta,
      epsilon, zeta) PKC isoforms; 2) PGE2 causes selective activation of PKC-delta,
      which likely mediates the action of PGE2 to reverse AVP inhibition of HCO-3
      absorption; and 3) PGE2 activation of PKC-delta requires the presence of AVP,
      which may explain the fact that PGE2 influences HCO-3 transport only when AVP is
      present.

PMID- 9176375
TI  - Expression of bcl-2 and bax in regenerating rat renal tubules following ischemic
      injury.
AB  - To define potential roles for bcl-2 and bax in adult kidney as regulators of
      regeneration, their expressions were characterized postischemic injury. A 2.1
      fold increase in levels of renal bcl-2 mRNA occurred within 24 h of injury
      relative to levels in kidney of sham-operated control rats. The levels of bcl-2
      mRNA remained elevated for 3 days but returned to baseline by day 5 postischemia.
      In situ hybridization of kidneys from sham-operated rats demonstrated faint
      expression of bcl-2 mRNA localized diffusely throughout the nephron. After renal
      injury, the expression of bcl-2 mRNA was markedly enhanced in regenerating
      proximal tubule cells relining the basement membrane. Immunohistochemistry showed
      a similar localization for bcl-2 protein. Levels of bax mRNA in kidney were
      elevated beginning at 24 h postischemia and remained elevated for 7 days
      postinjury. Bax mRNA and bax protein were colocalized to regenerating proximal
      tubules postischemia and were prominently expressed in papillary proliferations.
      We conclude that the expressions of bcl-2 and bax in kidney are enhanced in a
      predictable pattern following acute ischemic injury. Our findings suggest that
      these regulators of apoptosis play key roles in the process of repair of the
      damaged proximal tubule postischemia.

PMID- 9176376
TI  - Effect of chronic metabolic acidosis on thyroid hormone homeostasis in humans.
AB  - The effects of metabolic acidosis on thyroid function are unknown. We
      investigated the effects of chronic extrarenal acidosis on the hypothalamic
      pituitary-thyroid axis. Chronic metabolic acidosis was induced by administering
      NH4Cl (4.2 mmol.kg body wt-1.day-1) to six normal male volunteers during
      metabolic balance conditions. Plasma bicarbonate concentration decreased from
      25.0 +/- 0.4 to 15.5 +/- 0.9 mmol/l (P < 0.001). Metabolic acidosis significantly
      decreased serum-free 3,5,3'-triiodothyronine (T3) concentrations from 373 +/- 18
      (control) to 251 +/- 13 pg/dl (P < 0.001) and decreased serum-free L-thyroxine
      (T4) from 1.55 +/- 0.42 to 1.25 +/- 0.37 ng/dl (P < 0.002), whereas serum total
      reverse T3 did not change significantly. Consequently, the reverse T3-to-free T4
      ratio increased. Serum thyroid-stimulating hormone (TSH) levels increased
      significantly from 0.70 +/- 0.07 during control to 1.30 +/- 0.12 mU/l during
      acidosis (P < 0.003). The TSH response to thyrotropin (TRH, 2 mg intranasally)
      was exaggerated in acidosis: the partial area under the concentration curve for
      the TSH response (210 min post-TRH) was 902 +/- 167 during control compared with
      1.394 +/- 209 mU.min.l-1 during acidosis (P = 0.0139). Chronic metabolic
      acidosis, as produced by the model employed here, induces a decrease in thyroid
      hormone secretion and might exert additional effects on thyroid hormone
      metabolism in humans. The acidosis-induced decrease in thyroid function might
      modulate some of the reported effects of metabolic acidosis, such as on nitrogen
      balance, protein synthesis, lean body mass, insulin-like growth factor I levels,
      renal acidification, and cardiac contractile function.

PMID- 9176377
TI  - Segmental localization of urea transporter mRNAs in rat kidney.
AB  - Renal epithelia express at least two distinct urea transporter mRNAs, termed UT1
      and UT2, that are derived from a single UT gene by alternative splicing. Previous
      immunolocalization studies using a polyclonal antibody that does not distinguish
      between the protein products of these two transcripts revealed that expression of
      urea transporter protein is restricted to inner medullary collecting ducts and
      descending thin limbs of Henle's loop. To identify which transcripts account for
      protein expression in these two structures, we carried out reverse transcription
      polymerase chain reaction studies in microdissected structures using UT1- and UT2
      specific primers. UT1 mRNA was detected only in the inner medullary collecting
      duct, consistent with its identification as the vasopressin-regulated urea
      transporter. In contrast, UT2-mRNA was detected in the late part of descending
      thin limbs of short loops of Henle and in the inner medullary part of descending
      thin limbs of long loops of Henle. This localization is consistent with the
      predicted role of UT2 in medullary urea recycling. Thus, in conjunction with
      foregoing physiological studies, our data indicate that these transporters play
      central roles in the urinary concentrating mechanism.

PMID- 9176378
TI  - Expression of the insulin-like growth factor system in the hypokalemic rat
      kidney.
AB  - We studied the renal expression of the insulin-like growth factor (IGF) system to
      gain a better perspective of its potential role in the hyperplastic adaptation of
      the distal nephron to potassium deficiency. Rats were pair fed 1% or 0.002%
      potassium diets for periods up to 10 days. IGF-I mRNA was diminished in potassium
      deficient rats within 4 days, whereas mRNA for IGF binding protein-1 (IGFBP-1), a
      collecting duct-associated protein, was increased by day 7. At day 10 mRNA for
      IGFBP-1 in potassium-deficient animals averaged 2.07 +/- 0.53 (mean +/- SD,
      relative densitometry units) compared with 0.89 +/- 0.26 in control rats (n = 4,
      P = 0.002). Conversely, IGFBP-3, a binding protein whose mRNA has been localized
      to the interstitial compartment, averaged 2.40 +/- 0.02 in potassium-deficient
      rats and 4.77 +/- 0.05 in controls (n = 4, P < 0.03) at day 10 of treatment.
      Immunohistochemistry performed using a specific IGFBP-1 antibody revealed
      hyperplasia of distal nephron segments along with an increase in IGFBP-1 in
      potassium-depleted rats. These data suggest that IGFBP-1 may play an important
      role in the control of cellular adaptations in the hypokalemic rat kidney either
      directly by influencing cell migration or indirectly by localizing IGF-I to the
      distal nephron.

PMID- 9176379
TI  - Albumin endocytosis in OK cells: dependence on actin and microtubules and
      regulation by protein kinases.
AB  - We used proximal tubule-derived opossum kidney (OK) cells to determine the
      dependence of albumin endocytosis on regulation by protein kinases and on the
      cytoskeleton. Uptake was observed only across the apical but not the basolateral
      membrane and exceeded uptake in collecting duct-derived Madin-Darby canine kidney
      cells 14-fold. Inhibition of endocytosis via clathrin-coated vesicles but not via
      caveolae abolished uptake. Cytochalasin D reduced uptake to < 5% of control, and
      inhibition of microtubule polymerization by nocodazole reduced uptake to
      approximately 55% of control. Activation of protein kinase A (PKA) by adenosine
      3',5'-cyclic monophosphate, forskolin, or parathyroid hormone (PTH) reduced
      uptake to approximately 65% of control. Protein kinase C (PKC) activation did
      affect uptake to a similar extent as PKA activation but with a certain delay.
      Stimulation of PKG by guanosine 3',5'-cyclic monophosphate did not affect albumin
      endocytosis. The inhibitor of tyrosine kinases (TRK), genistein, induced an
      increase of uptake to approximately 160% of control. Reexocytosis of albumin was
      enhanced by PKC activation but not by PKA activation. TRK inhibition reduced the
      rate of reexocytosis. We conclude that albumin endocytosis in OK cells requires
      the integrity of the actin cytoskeleton. Microtubules facilitate endocytosis.
      Uptake is regulated by PKA, PKC, and TRK, yet with different time course and by
      different mechanisms, e.g., reexocytosis. Possibly TRK activity serves in a
      negative feedback loop to limit albumin endocytosis via a stimulation of
      reexocytosis.

PMID- 9176380
TI  - Localization and induction by dehydration of ClC-K chloride channels in the rat
      kidney.
AB  - We investigate the intrarenal expression of two recently cloned chloride
      channels, rClC-K1 and rClC-K2, by reverse transcriptase-polymerase chain reaction
      on single microdissected tubules from the rat kidney and by immunohistochemistry
      using a polyclonal antibody that recognizes both highly homologous channels. Both
      rClC-K1 and rClC-K2 mRNAs were detected in outer medullary late proximal tubules
      (S3), papillary ascending thin limbs (ATL), and outer medullary (MTAL) and
      cortical (CTAL) thick ascending limbs, distal tubules (DCT), and cortical, outer
      medullary, and inner medullary collecting ducts. Indirect immunofluorescence
      studies demonstrated that the rClC-K proteins were restricted to the basolateral
      membranes from ATL, DCT, and collecting ducts cells, whereas CTAL and MTAL
      exhibited a more diffuse basal staining. When rats were dehydrated, a condition
      which increased the expression of rClC-K1 in cortex and medulla, a weak
      cytoplasmic staining was found in late proximal tubule cells. Thus these results
      demonstrate that rat kidney ClC-K channels are predominantly located in the
      basolateral membranes from cells of the late segments of the renal tubule where
      most of chloride reabsorption takes place.

PMID- 9176381
TI  - Growth hormone-releasing hormone receptor mRNA in acromegalic pituitary tumors.
AB  - The growth hormone (GH)-releasing hormone receptor (GHRH-R) has been recently
      cloned and found to be a member of a new family of seven transmembrane receptors
      that includes secretin, vasoactive intestinal peptide, calcitonin, and
      corticotropin-releasing factor. GHRH-R mRNA has been demonstrated by Northern
      blot analyses to be present specifically in the anterior pituitary gland. To
      determine the precise cellular localization of this receptor in normal anterior
      pituitary and pituitary adenomas, GHRH-R mRNA was analyzed in 2 normal human
      pituitary glands and 16 human pituitary adenomas using in situ hybridization.
      GHRH-R was specifically localized in somatotroph cells in the normal pituitary.
      In the adenomas, all GH-producing adenomas originating from acromegalic patients
      demonstrated up-regulation of GHRH-R mRNA when compared with levels in the normal
      pituitary. Only one of five clinically nonfunctioning adenomas, a gonadotroph
      luteinizing hormone/follicle-stimulating hormone-positive adenoma, exhibited up
      regulation of this receptor message. Adrenocorticotrophic hormone-secreting and
      prolactin-secreting adenomas did not express GHRH-R message. In summary, GHRH-R
      is specifically expressed in somatotrophs and GH-producing adenomas, suggesting
      that GHRH-R may influence GH release in adenomas similar to this receptor's
      actions in the normal somatotrophs and may be involved in the growth of GH
      secreting adenomas.

PMID- 9176382
TI  - TIA-1 expression in lymphoid neoplasms. Identification of subsets with cytotoxic
      T lymphocyte or natural killer cell differentiation.
AB  - TIA-I is a 15-kd cytotoxic granule-associated protein expressed in natural killer
      (NK) cells and cytotoxic T lymphocytes. TIA-1 expression was evaluated by
      paraffin immunohistochemistry in 115 T- or NK-cell neoplasms, 45 B-cell
      neoplasms, and 45 Hodgkin's lymphomas. TIA-1-positive granules were identified
      within the cytoplasm of neoplastic cells in 6/6 large granular lymphocytic
      leukemias, 11/11 hepatosplenic T-cell lymphomas, 15/15 intestinal T-cell
      lymphomas, 6/6 NK-like T-cell lymphomas of no special type, 2/2 NK-cell
      lymphomas, 8/9 nasal T/NK-cell lymphomas, 7/8 subcutaneous T-cell lymphomas, 4/5
      pulmonary T- or NK-cell angiocentric lymphomas (lymphomatoid granulomatosis),
      12/19 T-cell anaplastic large-cell lymphomas, 2/12 nodal peripheral T-cell
      lymphomas, 1/3 CD8+ cutaneous T-cell lymphomas, and 5/38 classical Hodgkin's
      disease. All B-cell neoplasms, nodular lymphocyte-predominant Hodgkin's disease
      (7 cases), CD4+ cutaneous T-cell lymphomas (6 cases), adult T-cell
      leukemia/lymphomas (3 cases), T-cell chronic or prolymphocytic leukemias (3
      cases), and T-cell lymphoblastic leukemia/lymphomas (7-cases) were TIA-1
      negative. These findings indicate that most large granular lymphocytic leukemias,
      hepatosplenic T-cell lymphomas, intestinal T-cell lymphomas, NK-like T-cell
      lymphomas, NK-cell lymphomas, nasal T/NK-cell lymphomas, subcutaneous T-cell
      lymphomas, pulmonary angiocentric lymphomas of T or NK phenotype, and anaplastic
      large-cell lymphomas are cytotoxic T-or NK-cell neoplasms.

PMID- 9176383
TI  - Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in
      intraepidermal neutrophilic IgA dermatosis.
AB  - Intraepidermal neutrophilic IgA dermatosis, a rare skin disease entity manifested
      with blisters and pustules clinically and lower epidermal blister, acantholysis,
      and neutrophilic infiltration pathologically, was first reported in 1985.
      Although the disease is characterized by IgA autoantibodies targeting the
      epithelial cell surface component, the target antigen has not been determined. We
      investigated a patient with this disease by histopathology, direct and indirect
      immunofluorescence, immunoblotting, and immunoadsorption studies. The pustular
      lesion was characterized by blister at the lower epidermis, acantholysis, and
      neutrophilic infiltration. Nonsecretory IgA1 subclass autoantibodies targeting
      the lower epithelial cell surfaces were detected in the patient's skin and serum.
      The patient's IgA autoantibodies labeled a recombinant desmosomal protein
      desmoglein 3 on immunoblotting and the immunolabeling of epithelial cell surfaces
      was eliminated by preadsorption with desmoglein 3. Thus, desmoglein 3 is
      identified as a target antigen in intraepidermal neutrophilic IgA dermatosis. The
      ability of IgA1 autoantibodies to bind neutrophils may be responsible for the
      prominent neutrophilic infiltration observed histopathologically and for the
      pustular lesions observed clinically.

PMID- 9176384
TI  - Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the
      Lewis rat.
AB  - Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat
      shows pathological similarities to the human disease multiple sclerosis (MS).
      Rats that recover from EAE are essentially resistant to disease reinduction,
      unlike MS in which relapses are frequently associated with common bacterial and
      viral infections. As macrophage-derived interleukin (IL)-12 is a critical
      component of innate resistance to bacterial infection and appears to directly
      activate encephalitogenic T cells in vivo, the ability of this cytokine to
      reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by
      intraperitoneal IL-12 administration and could be reinduced up to 1 week after
      recovery from the primary clinical episode. Concomitant with worsening of initial
      clinical signs and relapse was an increase in the ratio of macrophages to T cells
      in brain stem perivascular cuffs and the expression of inducible nitric oxide
      synthase in cells with both macrophage and microglial morphology. These findings
      suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and
      relapse in patients with MS.

PMID- 9176385
TI  - Improved prognosis assessment for patients with bladder carcinoma.
AB  - Urothelial carcinomas are heterogeneous diseases with an aggressive clinical
      potential. To date, the most used prognostic factors for bladder carcinomas are
      grade and stage, which are based on histopathological parameters that are often
      not reliable in predicting a clinical outcome. Here, we evaluated the clinical
      outcome of 100 patients with urothelial carcinomas with follow-up information for
      more than 2 years after surgery in relation to the expression of two cell surface
      antigens, ie, E-cadherin and autocrine motility factor receptor (AMF-R, gp78).
      Frozen bladder tissues were serially cut, stained either with hematoxylin and
      eosin for grading, with the anti-gp78 antibodies, or with anti-E-cadherin
      antibodies to determine level of expression. Of 63 patients presented at the time
      of diagnosis with pathological loss of E-cadherin associated with increased gp78
      expression, 39 (62%) succumbed to tumor progression or death. Of 37 patients with
      normal E-cadherin and gp78 expression positive and negative, respectively, 36
      (97%) had favorable disease outcomes (P < 0.0001). The results suggest that in
      bladder carcinomas abnormal expression of both E-cadherin and gp78 results in a
      poor disease outcome, independent of tumor stage and grade.

PMID- 9176387
TI  - Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's
      disease.
AB  - In this study, we demonstrate that two important regulators of the cell cycle,
      cyclin-dependent kinase-4 and its inhibitor p16, are increased in the brains of
      cases of Alzheimer's disease patients compared with age-matched controls. Both
      proteins are increased in the pyramidal neurons of the hippocampus, including
      those neurons containing neurofibrillary tangles and granulovacuolar
      degeneration. As p16 is not normally found in terminally differentiated neurons,
      it seems paradoxical that it is increased in Alzheimer's disease unless it is
      responding to increases in cyclin-dependent kinase-4 or other cell cycle
      regulators. Induction of the latter, a protein that signals re-entry and
      progression through the cell cycle, may itself be the consequence of alpha
      response to a growth stimulus. Re-entry into the cell cycle is likely deleterious
      in terminally differentiated neurons and may contribute to the biochemical
      abnormalities, such as oxidative stress and hyperphosphorylated tau protein, as
      well as the neuronal degeneration characteristic of the pathology of Alzheimer's
      disease.

PMID- 9176386
TI  - Loss of heterozygosity and microsatellite instability in breast hyperplasia. No
      obligate correlation of these genetic alterations with subsequent malignancy.
AB  - Loss of heterozygosity and microsatellite instability have been often reported in
      breast cancer and seldom in proliferative breast disease (PBD). DNA samples from
      microdissected PBD lesions, including papillomas (25 lesions), from 8 women were
      analyzed by polymerase chain reaction for loss of heterozygosity and
      microsatellite instability at 10 loci including INT-2 oncogene locus, D17S796
      (the p53 gene region), and D17S579 (in the region of the BRCA-1 gene). In a
      patient, five loci with microsatellite instability and two loci with loss of
      heterozygosity were identified in one papilloma with florid hyperplasia and
      atypia, and 10 other PBD lesions were negative for genetic alteration (GA) and
      atypia. Three loci with microsatellite instability were identified in another PBD
      lesion without atypia, whereas another lesion from this second patient had
      minimal atypia without GAs. These two patients have been well for more than 20
      years. No other patient, including a woman developing cancer, had GAs. We
      detected GAs in PBD (25% of women, 8% of lesions). Incomplete correlation between
      GAs and anatomic atypia was suggested. It seems evident that several GAs in PBD
      lesions may not indicate clinically meaningful premalignancy for remaining
      breast.

PMID- 9176388
TI  - Immunophenotyping and gene rearrangement analysis provide additional criteria to
      differentiate between cutaneous T-cell lymphomas and pseudo-T-cell lymphomas.
AB  - Differentiation between cutaneous pseudo-T-cell lymphomas and cutaneous T-cell
      lymphomas (CTCLs) may be extremely difficult. In this study, it was investigated
      whether demonstration of an aberrant phenotype and detection of clonal T-cell
      receptor gamma (TCR gamma) gene rearrangements can be used as additional
      differential diagnostic criteria. Immunohistochemical studies and TCR gamma gene
      rearrangement analysis using a polymerase chain reaction with primers specific
      for V gamma 1-8 and V gamma 9 gene segments in combination with denaturing
      gradient gel electrophoresis (PCR/ DGGE) were performed on frozen material of 11
      pseudo-T-cell lymphomas and 17 CTCLs, including 9 cases of mycosis fungoides (MF)
      and 8 pleomorphic CTCLs. Clonal TCR gamma gene rearrangements were found in 66%
      of patch/plaque-stage MF and 100% of tumor-stage MF and pleomorphic CTCL, but not
      in any of 10 pseudo-T-cell lymphomas studied. Aberrant expression of CD2, CD3,
      and/or CD5 antigens was noted in 3 of 6 (50%) cases of patch/plaque-stage MF, all
      three cases of tumor-stage MF, and 5 of 8 (62%) pleomorphic CTCLs, but not in any
      of the 11 pseudo-T-cell lymphomas. Moreover, in pseudo-T-cell lymphomas
      exhibiting a nodular or diffuse growth pattern, a considerable admixture with
      reactive CD8+ T cells (15 to 60%), B cells (up to 20%), and macrophages was a
      characteristic finding. In conclusion, the results of this study suggest that
      demonstration of clonal TCR gene rearrangements and an aberrant phenotype, as
      well as demonstration of many admixed CD8+ T cells and B cells can be considered
      as useful additional criteria in the differentiation between pseudo-T-cell
      lymphomas and CTCLs.

PMID- 9176389
TI  - Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for
      the mechanism of lymphatic dissemination.
AB  - Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably,
      melanoma progression toward this metastasizing phenotype is accompanied by
      intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the
      formation of new lymph vessels in the tumor, has never been reported. To
      investigate how primary melanoma cells interact with the existing lymphatic
      microvasculature, and whether lymphangiogenesis occurs, an immunostaining was
      developed that differentially decorates blood and lymph vessels in frozen tissue
      sections. The density and distribution of both these vessel types in and around
      thin (< or = 1.5 mm) and thick (> or = 1.5 mm) primary melanoma lesions and in
      normal and uninvolved skin were determined. Although especially in thick melanoma
      lesions a significant increase in blood vessel density was observed, lymphatic
      density remained unaltered, showing that lymphangiogenesis did not occur.
      Morphological analysis indicated, however, that melanoma progression is
      accompanied by a sequence of events that involves hemangiogenesis supporting
      tumor expansion, especially in the vertical growth phase. Often, stromal sepia
      are formed around the blood capillaries in the tumor neovasculature protecting
      them from invasion. Lymph vessels inside the tumor were infrequently observed.
      However, subepidermal lymph vessels often seemed to be entrapped and penetrated
      by the expanding tumor mass. In this way, hemangiogenesis, as the driving force
      behind tumor expansion, might indirectly increase the chance of lymphatic
      invasion in the absence of lymphangiogenesis. This model explains the paradox
      that, although melanoma metastasis seems to require angiogenesis, a consistent
      relation of prognosis with blood capillary density in primary cutaneous melanoma
      is lacking.

PMID- 9176390
TI  - Genetically null mice reveal a central role for epidermal growth factor receptor
      in the differentiation of the hair follicle and normal hair development.
AB  - Mice harboring a targeted disruption of the epidermal growth factor receptor
      (EGFR) allele exhibit a severely disorganized hair follicle phenotype, fuzzy
      coat, and systemic disease resulting in death before 3 weeks. This skin phenotype
      was reproduced in whole skin grafts and in grafts of EGFR null hair follicle buds
      onto nude mice, providing a model to evaluate the natural evolution of skin
      lacking the EGFR. Hair follicles in grafts of null skin did not progress from
      anagen to telogen and scanning electron micrografts revealed wavy, flattened hair
      fibers with cuticular abnormalities. Many of the EGFR null hair follicles in the
      grafted skin were consumed by an inflammatory reaction resulting in complete hair
      loss in 67% of the grafts by 10 weeks. Localization of follicular differentiation
      markers including keratin 6, transglutaminase, and the hair keratins mHa2 and
      hacl-1 revealed a pattern of premature differentiation within the null hair
      follicles. In intact EGFR null mice, proliferation in the interfollicular
      epidermis, but not hair follicles, was greatly decreased in the absence of EGFR.
      In contrast, grafting of EGFR null skin resulted in a hyperplastic response in
      the epidermis that did not resolve even after 10 weeks, although the wound
      induced hyperplasia in EGFR wild-type grafts had resolved within 3 to 4 weeks.
      Thus, epithelial expression of the EGFR has complex functions in the skin. It is
      important in delaying follicular differentiation, may serve to protect the hair
      follicle from immunological reactions, and modifies both normal and wound-induced
      epidermal proliferation but seems dispensable for follicular proliferation.

PMID- 9176392
TI  - Expression of Bcl-2 family during liver regeneration and identification of Bcl-x
      as a delayed early response gene.
AB  - Induction of Bcl-2 and Bcl-x has been demonstrated in mitogen-stimulated
      lymphocytes in vitro, suggesting that these two apoptosis modulators may also
      play a role during proliferation. To explore this possibility in a physiological
      setting, mRNA expression of various Bcl-2 family members was examined during
      liver regeneration induced by partial hepatectomy, a well characterized in vivo
      model of cell cycle progression. After a 60% partial hepatectomy in C3H/HeN mice,
      the steady-state levels of Bcl-x mRNA exhibited a cyclical pattern, with peaks at
      4 hours (early G1) and 48 to 72 hours (G1 phase of the second hepatocyte cell
      cycle). A1 and Bcl-2 mRNA were not detected, and the levels of two Mcl-1 mRNA
      species remained low without significant changes. The three pro-apoptotic members
      of the family, Bak, Bad, and Bax, all showed an early decline in mRNA levels when
      Bcl-x transcripts increased, followed by later peaks at 12, 24, and 48 to 72
      hours, respectively. Experiments were subsequently conducted in C3H/HeJ mice, an
      endotoxin-resistant strain with slower liver regeneration marked by a protracted
      G1 phase. Even though immediate-early gene responses measured by c-myc induction
      remained intact, the timing of Bcl-x mRNA expression was delayed in C3H/HeJ mice.
      When C3H/HeN mice were pretreated with cycloheximide before hepatectomy, the
      early peak of Bcl-x mRNA at 4 hours was essentially abrogated whereas the
      immediate-early gene c-myc was hyperinduced, thus implicating Bcl-x as a delayed
      early response gene during liver regeneration. Bcl-x was localized in hepatocytes
      and by both immunohistochemistry and Western blot analysis, Bcl-xL protein
      reached highest levels at 12 hours (mid-G1), consistent with the expression of a
      delayed early gene. In summary, the expression profiles of Bcl-2 family members
      during liver regeneration suggest a cell-cycle-dependent regulation as well as a
      physiological role for these apoptosis-modulating genes during growth and
      proliferation.

PMID- 9176391
TI  - Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins
      and p120) in colorectal polyps.
AB  - E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma
      catenin and p120 protein play a crucial role in the maintenance of normal tissue
      architecture. Perturbation in any of these molecules results in loss of
      intercellular adhesion and cell transformation. In this study, we have used
      immunohistochemistry to localize E-cadherin, alpha-, beta-, and gamma-catenin,
      and p120 in paraffin-embedded tissues from 60 patients with colonic polyps.
      Specimens consisted of 20 samples each from hyperplastic, inflammatory, and
      sporadic adenomatous polyps. Ten histologically normal colonic samples were also
      studied. Normal colonic epithelial cells showed strong E-cadherin/ catenin/p120
      immunostaining at the cell-cell junction. In 65% (13/20) of adenomatous polyps,
      beta-catenin showed abnormal nuclear localization with increased expression and
      loss of membranous staining compared with the adjacent normal mucosa. In two
      cases (10%), gamma-catenin was seen in the nuclei. Heterogeneous p120
      immunoreactivity was observed in four cases (20%), of which two also showed beta
      catenin nuclear localization. Preserved membranous alpha-catenin staining was
      seen in all cases. E-cadherin was down-regulated in 6 of 20 (30%) adenomas with
      loss of cell surface staining in 3 cases. All hyperplastic and 40% (8/20) of
      inflammatory polyps showed weak E-cadherin expression on the surface epithelium.
      Similar changes in p120 expression were seen in all hyperplastic and 20% (4/20)
      of inflammatory polyps. There were no concomitant changes in alpha-, beta-, or
      gamma-catenin expression. These results indicate that changes in catenin
      expression and cellular localization occur early in dysplastic colonic lesions.

PMID- 9176394
TI  - Steroid hormone induction and expression patterns of L-plastin in normal and
      carcinomatous prostate tissues.
AB  - Application of differential display to the comparison of androgen-stimulated and
      unstimulated human prostate carcinoma cell line LNCaP identified androgen
      induction of the L-plastin gene, which encodes an actin-binding protein isoform.
      Further investigation demonstrated that L-plastin expression in LNCaP cells is up
      regulated by both dihydrotestosterone and estradiol. This induction of expression
      is detected as early as 2 hours after addition of steroids to the cell culture. L
      plastin expression is also detected in other prostate carcinoma cell lines by
      reverse transcriptase polymerase chain reaction and immunohistochemistry but not
      in the single normal adult prostate epithelial cell line that is available to us.
      Analysis of multiple primary prostatic tumor tissues as well as normal and tumor
      tissues of the same prostate gland showed that tumor tissues exhibit a higher
      level of expression as compared with the normal tissues. Immunohistochemical
      study using anti-L-plastin antiserum on normal and carcinomatous prostate tissues
      showed a very striking difference in the staining patterns. Positive staining was
      seen in the fibromuscular stroma in normal prostates but not in the glandular
      epithelial cells. In contrast, strong staining was seen predominantly within the
      carcinomatous glandular epithelial cells. Taken together, these results suggest
      that the expression of L-plastin in prostatic epithelial cells is linked to the
      malignant state and that, once expressed in carcinomas, its expression is
      regulated by steroid hormone receptors.

PMID- 9176393
TI  - Prognostic relevance of a novel proliferation marker, Ki-S11, for soft-tissue
      sarcoma. A multivariate study.
AB  - In 132 soft-tissue sarcomas and 52 benign soft-tissue tumors, cellular
      proliferation was examined by immunohistochemistry using monoclonal antibodies Ki
      S11 (Ki-67 antigen) and Ki-S1 (topoisomerase II alpha) and by flow cytometric
      analysis of the S-phase fraction (SPF). Malignant tumors were graded
      histologically according to the Federation Nationale des Centres de Lutte Contre
      le Cancer (FNCLCC) system. Patient age, sex, tumor location, histological type,
      and DNA ploidy were considered as additional prognostic variables. Consistent
      immunoreactivity was seen in approximately 95% of the cases, and determination of
      SPF was possible in approximately 60% Ki-S11 and Ki-S1 immunolabeling indices
      correlated in a linear manner. All proliferation parameters yielded significant
      differences between benign and malignant tumors. Ki-S11 and Ki-S1 immunoreactive
      scores also co-varied significantly with SPF, mitotic count, and
      histopathological grade. In univariate analysis, immunohistochemical
      proliferation indices, histopathological grade, mitotic count, and SPF were
      predictive of overall survival and the development of metastases. In multivariate
      analysis, immunolabeling scores of proliferation markers, grade, and SPF emerged
      as independent predictors of global survival and systemic progression. We
      conclude that the immunohistochemical assessment of proliferation, being more
      readily performable and more easily assessable than the equally relevant S phase
      fraction, may add appreciable information to the current prognostic models for
      soft-tissue sarcoma.

PMID- 9176395
TI  - Sublytic concentrations of the membrane attack complex of complement induce
      endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear
      factor-kappa B activation.
AB  - Activation of the complement cascade and subsequent assembly of the membrane
      attack complex (MAC) occur in a number of pathophysiological settings. When
      formed on the surface of endothelial cells in sublytic concentrations, the MAC
      can induce a number of proinflammatory activities, including the secretion of
      soluble mediators (eg, interleukin (IL)-8 and monocyte chemoattractant protein
      (MCP)-1) and the up-regulation of cell surface adhesion molecules. Available data
      indicate that MAC-induced cell activation may occur through several complex
      signal transduction pathways, but little is known about the intranuclear
      mechanisms by which complement-derived products promote the up-regulation of
      inflammatory mediators. Using purified distal complement proteins (C5-9) to
      assemble functional MAC on early-passage human umbilical vein endothelial cells
      (HUVECs), we examined mechanisms of MCP-1 and IL-8 induction. Formation of
      sublytic concentrations of MAC promoted an increase in nuclear factor (NF)-kappa
      B DNA binding activity within 60 minutes as determined by serial electrophoretic
      mobility shift assay. Cytosolic to nuclear translocation of NF-kappa B was
      confirmed by Western immunoblot and immunocytochemical analyses. Formation of the
      C5b-8 complex also promoted NF-kappa B translocation but to a lesser degree than
      observed in HUVECs containing complete MAC. No cytosolic to nuclear translocation
      of the p65 NF-kappa B subunit was observed in unstimulated HUVECs or in cells
      incubated with the MAC components devoid of C7. Preincubation of HUVECs with
      pyrrolidine dithiocarbamate prevented MAC-induced increases in IL-8 and MCP-1
      mRNA concentrations and protein secretion. A direct cause and effect linkage
      between MAC assembly and NF-kappa B activation was established through
      examination of the pharmacological effect of the peptide SN50 on IL-8 and MCP-1
      expression. SN50 is a recently engineered 26-amino-acid peptide that contains a
      lipophilic cell-membrane-permeable motif and a nuclear localization sequence that
      specifically competes with the nuclear localization sequence of the NF-kappa B
      p50 subunit. This study provides direct in vitro evidence that the distal
      complement system (MAC) can promote proinflammatory endothelial cell activation,
      specifically, increases in IL-8 and MCP-1 mRNA concentrations and protein
      secretion, and that cytosolic to nuclear translocation of NF-kappa B is necessary
      for this response.

PMID- 9176397
TI  - Expression of macrophage colony-stimulating factor and its receptor in hepatic
      granulomas of Kupffer-cell-depleted mice.
AB  - In mice administered with liposome-entrapped dichloromethylene diphosphonate,
      which depletes Kupffer cells, the size and the number of zymosan-induced
      granulomas in the liver were smaller than in untreated mice. The number of
      macrophage precursors, as detected by the monoclonal antibodies for macrophage
      precursors, increased after zymosan injection in both groups of mice,
      proliferated, and differentiated into macrophages. Expression of macrophage
      colony-stimulating factor (M-CSF), interleukin-1, monocyte chemoattractant
      protein-1, tumor necrosis factor-alpha, and interferon-gamma mRNA was enhanced in
      the stage of granuloma formation in the control mouse liver, whereas it was
      suppressed in Kupffer-cell-depleted mice. However, M-CSF mRNA expression was
      increased in the Kupffer-cell-depleted mice to form granulomas in the late
      stages. In situ hybridization demonstrated the expression of M-CSF mRNA and c-fms
      mRNA in Kupffer cells and monocyte-derived macrophages in the sinusoid and
      granulomas. The concentration of M-CSF in serum of zymosan-injected control mice
      was within normal range, but that of zymosan-treated or untreated Kupffer-cell
      depleted mice was markedly elevated at day 1. These findings imply that Kupffer
      cells are indispensable for granuloma formation and produce various cytokines
      including M-CSF. The local production and consumption of M-CSF in the liver may
      play a crucial role in granulomatous inflammation.

PMID- 9176396
TI  - Adult Schistosoma mansoni worms positively modulate soluble egg antigen-induced
      inflammatory hepatic granuloma formation in vivo. Stereological analysis and
      immunophenotyping of extracellular matrix proteins, adhesion molecules, and
      chemokines.
AB  - Synchronized liver granulomas were induced by injecting Sepharose beads to which
      SEA soluble egg antigen (SEA) or the concanavalin A binding fraction of SEA had
      been coupled into a mesenteric vein in naive, single-sex (35 days) and bisexually
      (28 days) Schistosoma mansoni-infected and Plasmodium berghei-immunized mice.
      Stereological analysis revealed that peak granuloma formation was already reached
      8 days after injection in single-sex infected mice compared with 16 days in naive
      animals. No difference in granuloma formation between naive and P. berghei
      immunized animals and between unisexually and bisexually S. mansoni-infected mice
      was observed. This suggests that the positive immunomodulatory effect on the
      granulomogenesis is worm specific and not likely to be due to arousal of the
      immune system by unrelated factors, nor is it influenced by the gender or degree
      of maturation of female worms. At all stages in time, the concanavalin A binding
      fraction-induced granulomas reached only 65 to 70% of the volume of SEA-induced
      granulomas. Immunophenotyping of extracellular matrix proteins around deposited
      heads revealed that fibronectin was the dominant extracellular matrix protein and
      that also type I and IV collagen and laminin were deposited. Temporal analysis of
      the expression of the adhesion molecules ICAM-1, LFA-1, VLA-4, and VLA-6 was
      performed. Morphological evidence is presented for the role of adhesion molecules
      in the initiation and maintenance of hepatic granuloma formation. The chemokine
      monocyte chemoattractant protein-1 was expressed in the granuloma and in hepatic
      artery branches. From these data, it is concluded that adult S. mansoni worms
      positively modulate schistosomal hepatic granuloma formation in vivo. Adhesion
      molecules and chemokines play important roles in schistosomal granuloma
      formation.

PMID- 9176398
TI  - Intracellular viral localization in murine coxsackievirus-B3 myocarditis.
      Ultrastructural study by electron microscopic in situ hybridization.
AB  - Group B Coxsackieviruses are a common cause of myocarditis. To detect the viral
      genome and its localization in the myocardium, we examined C3H/He mice with
      Coxsackievirus B3 (CVB3) myocarditis on days 5, 8, and 14 after inoculation by
      the reverse transcriptase polymerase chain reaction and by in situ hybridization.
      Sense and antisense CVB3 RNA were detected in the myocardium of all mice up to
      day 14 by reverse transcriptase polymerase chain reaction. Light microscopic in
      situ hybridization with a cDNA probe for CVB3 showed clusters of positive signals
      in the areas of myocardial necrosis and cell infiltration. With electron
      microscopic in situ hybridization, CVB3 RNA was detected in the cytoplasm of
      cardiocytes, between the myofibrils, near the mitochondria, and in tubular or
      vesicular structures. Viral RNA was also detected in necrotic debris, in the
      cytoplasm of macrophages, and in the cytoplasm of interstitial fibroblasts. These
      findings suggest that CVB3 RNA is replicated in the cytoplasm of cardiocytes,
      transferred into tubular or vesicular structures, released into the interstitium,
      and phagocytosed by macrophages. Some positive signals were also detected in the
      cytoplasm of cardiocytes showing close contact with infiltrating lymphocytes,
      suggesting that the lymphocytes recognized virus-infected cardiocytes and caused
      cell-mediated immune cardiocyte damage.

PMID- 9176400
TI  - Troponin T cross-linking in human apoptotic cardiomyocytes.
AB  - Intracellular calcium overload of guinea pig cardiomyocytes is accompanied by
      troponin T cross-linking, which is revealed by changes in immunoreactivity of
      anti-troponin T antibodies. We presently investigated whether the same process is
      detectable in the human heart. Immunohistochemistry shows myofibrillar staining
      with BN-59 anti-troponin T antibody with rare cardiomyocytes in samples obtained
      at surgery, whereas approximately 50% of myocytes are labeled in heart samples
      taken at autopsy within 3 hours of death, and every cardiomyocyte is stained
      after exposure of biopsy sections to 10 mmol/L calcium. Western blot analysis
      shows reactive polypeptides of approximately 70 and 85 to 90 kd in addition to
      troponin T in both treated and autopsy heart sections. Neither reactivity in
      immunohistochemistry nor additional reactive polypeptides in Western blot are
      detectable when calpain or transglutaminase is inhibited during exposure of
      sections to high calcium. Troponin T crosslinking occurs also in isolated
      myofibrils, which show staining with BN-59 at either sarcomeric A or I bands.
      Labeling with TdT-mediated dUTP nick and labeling (TUNEL) to demonstrate
      apoptosis reveals DNA fragmentation in BN-59-positive myocytes. Thus, troponin T
      cross-linking occurs in human cardiac myocytes concomitantly with apoptosis and
      autopsy autolysis, suggesting that similar cytosolic alterations can be produced
      by different types of myocyte death.

PMID- 9176399
TI  - Location of type XV collagen in human tissues and its accumulation in the
      interstitial matrix of the fibrotic kidney.
AB  - An antipeptide antibody was produced against the carboxyl-terminal noncollagenous
      domain of human type XV collagen and used to localize this recently described
      collagen in a number of human tissues. The most conspicuous findings were
      powerful staining of most of the capillaries and staining of the basement
      membrane (BM) zones of muscle cells. Not all of the BM zones were positive,
      however, as shown by the lack of staining in the developing fetal alveoli and
      some of the tubules in developing kidney. Nor was type XV collagen staining
      restricted to the BM zones, as some could be observed in the fibrillar collagen
      matrix of the papillary dermis and placental villi, for example. Interestingly,
      differences in the expression of type XV collagen could be observed during kidney
      development, and staining of fetal lung tissue suggested that changes in its
      expression may also occur during the formation of vascular structures. Another
      intriguing finding was pronounced renal interstitial type XV collagen staining in
      patients with kidney fibrosis due to different pathological processes. This
      suggests that the accumulation of type XV collagen may accompany fibrotic
      processes. Full-length human type XV collagen chains with an apparent molecular
      mass of approximately 200 kd were produced in insect cells using a baculovirus
      expression system. The fact that these had a markedly higher molecular mass than
      the 100- to 110-kd type XV collagen chains found in homogenates of heart and
      kidney tissue suggests either proteolytic processing during the synthesis of type
      XV collagen or an inability to solubilize complete molecules from tissues.

PMID- 9176401
TI  - Early events of metastasis in the microcirculation involve changes in gene
      expression of cancer cells. Tracking mRNA levels of metastasizing cancer cells in
      the chick embryo chorioallantoic membrane.
AB  - The early events of metastasis involve multiple interactions between cancer cells
      and the host microcirculation during cancer cell arrest, adhesion, and
      extravasation. These interactions may lead to changes in gene expression of the
      metastasizing cancer cells, although such changes have never been demonstrated
      directly. To test this hypothesis, B16-F10 murine melanoma cells were injected
      intravenously into the chick embryo chorioallantoic membrane (CAM), and mRNA
      levels in the metastasizing cancer cells were evaluated by species-specific
      reverse transcription polymerase chain reaction. Unlike standard mouse models of
      experimental metastasis, the CAM model showed successful extravasation of a large
      number of the arrested cancer cells in the CAM microcirculation without
      significant cancer cell death, providing a unique opportunity to keep track of
      mRNA levels in cancer cells during the early phases of metastasis. Using this
      model, we were able to demonstrate directly the temporal induction of cancer cell
      genes that potentially affect metastatic efficiency, namely, Fos (5 to 60 minutes
      after injection), vascular permeability factor (4 to 7 hours), and urokinase
      plasminogen activator (> 9 hours). In conclusion, using the CAM system, we have
      observed an alteration of gene expression in cancer cells in the early phases of
      metastasis, most likely as a consequence of host-cancer cell interactions. These
      changes may influence the metastatic behavior of cancer cells.

PMID- 9176402
TI  - Expression of functional VCAM-1 by cultured nasal polyp-derived microvascular
      endothelium.
AB  - Induction of endothelial vascular cell adhesion molecule-1 (VCAM-1) by
      interleukin (IL)-4 is believed to exert a major impact on the extravasation of
      leukocyte subsets in allergic disease. This notion has recently been challenged
      because cultured microvascular endothelial cells (ECs) derived from various
      organs are unable to express VCAM-1 after exposure to IL-4. In this study, we
      have established a method for isolation and culture of nasal polyp-derived
      microvascular ECs and report their cytokine-regulated VCAM-1 expression. With a
      combination of cell enzyme-linked immunosorbent assay, flow cytometry, and
      reverse transcription polymerase chain reaction, such expression was shown to be
      induced in a dose- and time-dependent manner not only by IL-1 beta and tumor
      necrosis factor-alpha but also by IL-4 and IL-13. Therefore, the response of
      nasal microvascular ECs did not harmonize with that of counterparts from several
      other tissues. IL-4 or IL-13 combined with submaximal concentrations of IL-1 beta
      or tumor necrosis factor-alpha increased VCAM-1 expression in a synergistic
      manner. VCAM-1 was functional as shown by antibody-mediated inhibition of
      leukocyte adhesion. Taken together, our results supported the notion that
      selective VCAM-1 induction by IL-4 and IL-13 plays an important role for the
      preferential recruitment of eosinophils and T lymphocytes seen in human airways
      affected by allergy.

PMID- 9176403
TI  - Antisense E1AF transfection restrains oral cancer invasion by reducing matrix
      metalloproteinase activities.
AB  - E1AF is a newly identified human ets-family transcription factor. We have
      reported that E1AF can up-regulate transcription of matrix metalloproteinase
      (MMP) genes and confers invasive phenotype on human cancer cells. HSC3 is an oral
      squamous-cell-carcinoma-derived cell line, and it manifests high levels of E1AF
      and MMP-1 and -9 gene expression that are associated with invasive potential. We
      reconstructed an E1AF antisense expression vector, transfected HSC3 cells with
      the vector, and obtained HSC3AS cells that express E1AF antisense RNA. HSC3AS
      showed decreasing mRNA and protein levels of MMP-1, -3, and -9. Moreover, HSC3AS
      showed lower invasive potential in vitro three-dimensional raft culture and in
      vivo implantation into nude mice. These results imply that transfection of
      antisense E1AF inhibits tumor invasion by down-regulating MMP genes.

PMID- 9176404
TI  - Phenotypic diversity of neoplastic chondrocytes and extracellular matrix gene
      expression in cartilaginous neoplasms.
AB  - Chondrocyte differentiation is characterized by distinct cellular phenotypes,
      which can be identified by specific extracellular matrix gene expression
      profiles. By applying in situ analysis on the mRNA and protein level in a series
      of benign and malignant human chondrogenic neoplasms, we were able to identify
      for the first time different phenotypes of neoplastic chondrocytes in vivo: 1)
      mature chondrocytes, which synthesized the characteristic cartilaginous
      extracellular tumor matrix, 2) cells resembling hypertrophic chondrocytes of the
      fetal growth plate, 3) cells resembling so-called dedifferentiated chondrocytes,
      and 4) well differentiated chondrocytic cells, which expressed type I collagen,
      indicating the presence of post-hypertrophic differentiated neoplastic
      chondrocytes. Chondrocytes exhibiting a range of phenotypes were found to be
      present in the same neoplasm. The different observed phenotypes, including the
      dedifferentiated phenotype, were in contrast to the anaplastic cells of high
      grade chondrosarcomas. Comparison of expression data with tumor morphology
      revealed a relationship between the cellular phenotypes, the tumor matrix
      composition, and the matrix and cell morphology within the neoplasms. The
      distinctly different phenotypes of neoplastic chondrocytes are the basis of the
      characteristic high biochemical and morphological heterogeneity of chondroid
      neoplasms and shed light on their biological and clinical behavior.

PMID- 9176405
TI  - Molecular detection of tumor-associated antigens shared by human cutaneous
      melanomas and gliomas.
AB  - Both melanocytes and glial cells are derived embryologically from the neural
      ectoderm. Their malignant transformed counterparts, melanoma and glioma cells,
      respectively, may share common antigens. Numerous tumor-associated antigens have
      been identified in melanomas but only a few a gliomas. Using an established
      reverse transcriptase polymerase chain reaction plus Southern blot assay, we
      compared the mRNA expression of melanoma-associated antigens (MAAs) of melanomas
      to brain tumors primarily derived from glial cells. The MAAs studied included
      tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2), gp100,
      human melanoma antigen-encoding genes 1 and 3 (MAGE-1 and MAGE-3), and
      melanotransferrin (p97). Glioblastoma multiforme (n = 21), anaplastic astrocytoma
      (n = 3), ependymoma (n = 2), meningioma (n = 3), oligodendroglioma (n = 1), and
      melanoma (n = 12) tumor specimens were assayed for MAA mRNA expression.
      Glioblastoma multiforme, astrocytoma, and melanoma cell lines were also assayed.
      We observed that individual MAA mRNAs were expressed in these brain tumors and
      cell lines at varying frequencies. The melanogenesis-pathway-related MAAs Tyr,
      TRP-1, TRP-2, and gp100 mRNAs were also expressed at different levels in normal
      brain tissues but at a much lower frequency than in glioblastoma multiforme and
      melanoma. MAGE-1 and MAGE-3 mRNA were expressed in different types of tumor
      specimens and cell lines but never in normal brain tissue. Tumor antigen p97 was
      expressed in all types of tumors and also in normal brain tissues. These studies
      demonstrate that melanomas and primary brain tumors express common MAAs and could
      be exploited in patients with malignant glioma by active specific immunotherapy
      against these common MAAs.

PMID- 9176406
TI  - Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome
      inactivation and cytogenetics of a clinically benign smooth muscle proliferation.
AB  - Disseminated peritoneal leiomyomatosis (DPL, leiomyomatosis peritonealis
      disseminata) is a rare condition in which multiple histologically benign smooth
      muscle tumorlets diffusely stud peritoneal and omental surfaces in females,
      predominantly of reproductive age. Although the distribution of these lesions
      suggests a metastatic process, DPL generally has a benign clinical course and has
      been regarded as a metaplastic process. We assessed clonality of 42 tumorlets and
      15 normal tissues from four females with DPL by analyzing X chromosome
      inactivation as indicated by the methylation status of the androgen receptor gene
      (HUMARA). In each of the four patients, the same parental X chromosome was
      nonrandomly inactivated in all tumorlets, consistent with a metastatic unicentric
      neoplasm, or alternatively, selection for an X-linked allele in clonal
      multicentric lesions. Anomalous demethylation of the marker for X inactivation
      (HUMARA) was associated with loss of heterozygosity for markers spanning the X
      chromosome, or monosomy X, in part of one leiomyomatous lesion. Biallelic
      demethylation of the HUMARA microsatellite polymorphism was also found in one
      intramural leiomyoma. Two of six DPL lesions karyotyped had cytogenetic
      abnormalities involving chromosomes 7, 12, and 18, suggesting a pathogenesis in
      common with uterine leiomyomas.

PMID- 9176407
TI  - Experimental evidence for the origin of ductal-type adenocarcinoma from the
      islets of Langerhans.
AB  - To investigate the role of the islets of Langerhans in pancreatic carcinogenesis,
      freshly isolated islets from male Syrian hamsters were transplanted into the
      right submandibular glands of 50 female hamsters that were or were not pre
      treated with streptozotocin. Thyroid gland fragments, cellulose powder, and
      immortal hamster pancreatic ductal cells were injected into the left
      submandibular gland of the same hamsters. All recipient hamsters were then
      treated with the potent pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine
      weekly at a dose of 40 mg/kg of body weight for 3 weeks. Between 3 and 8 weeks
      later, 18 of 75 (24%) hamsters developed large ductal-type adenocarcinomas in the
      submandibular gland region, where islets were transplanted, but none developed
      tumors in the left submandibular gland. In 9 of 18 hamsters, tumors were multiple
      so that a total of 31 cancers were found. Eleven of these carcinomas were in the
      vicinity of transplanted islets, eight of which showed intra-insular ductular or
      cyst formation as seen in the pancreas of hamsters during pancreatic
      carcinogenesis. The formation of ductular structures within islets was also
      demonstrated in vitro. Some tumor cells in the vicinity of these islets were
      reactive with anti-insulin. Y chromosome message was found by polymerase chain
      reaction analysis in one of the three tumors examined. Also, like the induced
      pancreatic tumors, all three submandibular gland tumors that were examined had
      the mutation of the c-Ki-ras oncogene at codon 12 and all tumors expressed blood
      group A antigen. These and other findings strongly suggest that some components
      of islets, most probably stem cells, are the origin of ductal-type
      adenocarcinomas in this model.

PMID- 9176409
TI  - Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated
      variants that protect against infection with the cardiovirulent wild-type strain.
AB  - Coxsackievirus B3 (CVB3) is the enterovirus most frequently involved in human
      myocarditis or dilated cardiomyopathy. Attenuated variants were derived from a
      cardiovirulent CVB3 reactivated from a sequenced, full-length cDNA clone. The
      prophylactic potential of these variants was assessed in SWR/Ola (H-2q) mice.
      Animals immunized with attenuated variants of CVB3 were protected from
      myocarditis when challenged subsequently with the cardiovirulent wild-type virus.
      In contrast to nonimmunized controls, the wild-type virus was not isolated from
      myocardium of protected mice, nor was viral RNA detected in myocardium by reverse
      transcription nested polymerase chain reaction. Specific antibody to CVB3 was
      demonstrated by virus neutralization assay and by indirect immunofluorescence.
      The attenuated phenotype of one variant, p14V-1, remained stable throughout 20
      consecutive passages in SWR mice and induced a markedly lower level of
      autoantibody against mouse cardiac myosin heavy chain than the cardiovirulent
      wild type. These data demonstrate that attenuated strains protect against CVB3
      induced myocarditis in mice, that the attenuated phenotype is stable, and that
      they do not persist in myocardium nor induce a significant level of anti-heart
      anti-body against myosin heavy chain. These attenuants may be the basis of a live
      vaccine against CVB3 in the prevention of enteroviral heart muscle disease.

PMID- 9176408
TI  - Free fatty acids stimulate the polymerization of tau and amyloid beta peptides.
      In vitro evidence for a common effector of pathogenesis in Alzheimer's disease.
AB  - Alzheimer's disease is a degenerative disorder of the central nervous system,
      characterized by the concomitant deposition of extracellular filaments composed
      of beta-amyloid peptides and intracellular filaments composed of the microtubule
      associated protein tau. We have discovered that free fatty acids (FFAs) stimulate
      the assembly of both amyloid and tau filaments in vitro. The minimal
      concentration of arachidonic acid observed to stimulate tau assembly ranged from
      10 to 20 mumol/L, depending on the source of the purified tau. Tau preparations
      that do not exhibit spontaneous assembly were among those induced to polymerize
      by arachidonic acid. All long-chain FFAs tested enhanced assembly to some extent,
      although greater stimulation was usually associated with unsaturated forms.
      Utilizing fluorescence spectroscopy, unsaturated FFAs were also demonstrated to
      induce beta-amyloid assembly. The minimal concentration of oleic or linoleic acid
      observed to stimulate the assembly of amyloid was 40 mumol/L. The filamentous
      nature of these thioflavin-binding amyloid polymers was verified by electron
      microscopy. These data define a new set of tools for examining the polymerization
      of amyloid and tau proteins and suggest that cortical elevations of FFAs may
      constitute a unifying stimulatory event driving the formation of two of the
      obvious pathogenetic lesions in Alzheimer's disease.

PMID- 9176410
TI  - Spectrum and subcellular determinants of fluorinated anesthetic-mediated proximal
      tubular injury.
AB  - Currently used fluorinated anesthetics are chemically related to methoxyflurane
      (MF), a drug that caused many cases of clinical acute renal failure during
      previous widespread use. To determine whether newer fluorinated anesthetics might
      also have nephrotoxic effects, three currently used agents (isoflurane (IF),
      sevoflurane (SF), and desflurane) or MF were added to rat proximal tubular
      segments, followed by assessments of cell integrity (ATP levels and percent
      lactic dehydrogenase release). Ether served as a negative control. MF, IF, and SF
      each induced lethal proximal tubular segment injury (up to 92, 71, and 30% lactic
      dehydrogenase release, respectively) and massive ATP depletion. ATP losses were
      observed at or near clinically relevant drug levels, they preceded lethal injury,
      and they correlated with approximately 50% and approximately 100% reductions in
      total and Na,K-ATPase-driven respiration, respectively. Clinically relevant
      inorganic fluoride levels simulated fluorinated anesthetic toxicity. However,
      fluoride release from the anesthetics (a cytochrome P450 process) did not appear
      to be required for toxicity (no protection with P450 inhibitors and no detectable
      inorganic fluoride release). As IF was judged to be one-third as toxic as MF,
      subclinical tubular injury (increased urine N-acetyl-beta-D-glucosaminidase (NAG)
      levels) after its use was sought in 19 surgical patients. Fifteen patients
      undergoing comparable operations with SF (approximately one-half as toxic as IF
      in vitro) and nine patients undergoing regional/ local anesthesia were controls.
      The IF group doubled its urinary NAG levels by the end of surgery (P < 0.005).
      Conversely, NAG levels remained stable in both control groups. The conclusions
      are that 1) currently used fluorinated anesthetics, particularly IF, share (but
      to a lesser degree) MFs tubulotoxic effects, 2) ATP depletion (probably due to
      decreased production) and Na,K-ATPase inhibition are likely contributing
      mechanisms, 3) fluoride is a prime determinant of this toxicity, and 4) tubular
      injury can be expressed at or near clinically relevant anesthetic/inorganic
      fluoride levels. That increased enzymuria can develop in patients after IF
      anesthesia suggests that the above in vitro data could have potential clinical
      relevance in selected patients.

PMID- 9176411
TI  - Evidence for the genetic control of estradiol-regulated responses. Implications
      for variation in normal and pathological hormone-dependent phenotypes.
AB  - The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic
      and uterotropic responses in vivo. For example, the administration of E2 to
      ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific
      inflammatory infiltrates. In this study, we quantitated the number of eosinophils
      and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2
      treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All
      three strains exhibited a significant increase in the number of uterine
      eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3
      F1 hybrid mice responded with a greater number of infiltrating eosinophils and
      macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells
      showed that E2 treatment either down-regulates or does not affect the number of
      such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x
      C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus
      controlling the number of eosinophils infiltrating the uterus after E2 treatment,
      to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10
      and 16 was detected and evidence for locus interaction is presented. Our results
      conclusively demonstrate that E2-regulated/ dependent responses can be
      genetically controlled, indicating that the phenotypic variation observed in both
      the normal and pathological effects of E2 may, in part, be due to a genetic
      component.

PMID- 9176412
TI  - Differential rescue of the renal and hepatic disease in an autosomal recessive
      polycystic kidney disease mouse mutant. A new model to study the liver lesion.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is characterized by biliary
      and renal lesions that produce significant morbidity and mortality. The biliary
      ductual ectasia and hepatic portal fibrosis associated with ARPKD have not been
      well studied even though such lesions markedly affect the clinical course of
      patients after renal replacement therapy such as dialysis or transplantation.
      Here we describe the generation of a new mouse model to study the hepatic lesions
      associated with polycystic kidney disease. This model was generated by
      differentially rescuing the renal pathology in the orpk mutant mouse that
      displays a hepatorenal pathology that is similar to that seen in human patients
      with ARPKD. This was accomplished by expressing, as a transgene in the mutant
      animals, the cloned wild-type version of the gene associated with the mutant
      locus in this line of mice. Although renal function in the rescue animals is
      normal, the liver still exhibits biliary and ductular hyperplasia along with
      varying degrees of hepatic portal fibrosis that is indistinguishable from that in
      the mutant animals. Most important, the rescue animals survive significantly
      longer than mutants and will permit a more detailed analysis of the clinical and
      cellular pathophysiology of the hepatic defect associated with this disease.

PMID- 9176414
TI  - Some final responses to Dr. Waugh.

PMID- 9176413
TI  - Respiratory reovirus 1/L induction of intraluminal fibrosis. A model for the
      study of bronchiolitis obliterans organizing pneumonia.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a term that was first
      applied in 1985 to describe a long-observed but unclassified pattern of acute
      lung injury. BOOP lesions are characterized by fibrous extensions into the
      alveolar spaces in association with a peribronchiolar organizing pneumonia. Since
      1985, an increasing number of reports of BOOP have appeared in the clinical
      literature, and it is now accepted that BOOP is a significant pulmonary syndrome.
      Although BOOP can be associated with a number of documented pulmonary insults,
      many cases are not associated with known causes and are thus classified as
      idiopathic. The lack of an appropriate small animal model that closely mimics the
      generation of BOOP lesions has been an impediment to basic studies of the
      pathogenic mechanisms responsible for the generation of BOOP in humans. In this
      report, we describe an animal model for BOOP in which CBA/J mice infected with
      reovirus serotype 1/strain Lang develop BOOP lesions. These lesions closely
      resemble those seen in humans and occur in a well defined temporal sequence that
      proceeds from initial peribronchiolar inflammatory lesions to characteristic,
      fibrotic cellular BOOP lesions over a 3-week time course.

PMID- 9176415
TI  - Some final responses to Dr. Waugh.

PMID- 9176416
TI  - Osteoporosis.

PMID- 9176417
TI  - Keeping kids away from guns.

PMID- 9176418
TI  - Psychotherapy and chronic illness.

PMID- 9176419
TI  - Variation in emergency department use of cervical spine radiography for alert,
      stable trauma patients.
AB  - OBJECTIVE: To, assess the emergency department use of cervical spine radiography
      for alert, stable adult trauma patients in terms of utilization, yield for injury
      and variation in practices among hospitals and physicians. DESIGN: Retrospective
      survey of health records. SETTING: Emergency departments of 6 teaching and 2
      community hospitals in Ontario and British Columbia. PATIENTS: Consecutive alert,
      stable adult trauma patients seen with potential cervical spine injury between
      July 1, 1994, and June 30, 1995. MAIN OUTCOME MEASURES: Total number of eligible
      patients, referral for cervical spine radiography (overall, by hospital and by
      physician), presence of cervical spine injury, patient characteristics and
      hospitals associated with use of radiography. RESULTS: Of 6855 eligible patients,
      cervical spine radiography was ordered for 3979 (58.0%). Only 60 (0.9%) patients
      were found to have an acute cervical spine injury (fracture, dislocation or
      ligamentous instability); 98.5% of the radiographic films were negative for any
      significant abnormality. The demographic and clinical characteristics of the
      patients were similar across the 8 hospitals, and no cervical spine injuries were
      missed. Significant variation was found among the 8 hospitals in the rate of
      ordering radiography (p < 0.0001), from a low of 37.0% to a high of 72.5%. After
      possible differences in case severity and patient characteristics at each
      hospital were controlled for, logistic regression analysis revealed that 6 of the
      hospitals were significantly associated with the use of radiography. At 7
      hospitals, there was significant variation in the rate of ordering radiography
      among the attending emergency physicians (p < 0.05), from a low of 15.6% to a
      high of 91.5%. CONCLUSIONS: Despite considerable variation among institutions and
      individual physicians in the ordering of cervical spine radiography for alert,
      stable trauma patients with similar characteristics, no cervical spine injuries
      were missed. The number of radiographic films showing signs of abnormality was
      extremely low at all hospitals. The findings suggest that cervical spine
      radiography could be used more efficiently, possibly with the help of a clinical
      decision rule.

PMID- 9176421
TI  - Piety and prejudice. In his respect for the Jewish people, Osler was less a man
      of his time than a man of his profession.

PMID- 9176420
TI  - Ensuring access to abortion in an era of cutbacks.

PMID- 9176422
TI  - Duty and healing: the lifework of Benjamin Freedman.

PMID- 9176423
TI  - Osler and the Jewish people.
AB  - In his writings and actions, Sir William Osler betrayed no evidence of anti
      Semitism. In his era, this trait was unusual. Two of his articles, "Letter from
      Berlin" and "Israel and medicine," dealt directly with his thoughts on the Jewish
      people. In both he spoke out against anti-Semitism. Osler had friendships with
      Jewish colleagues--an example is the great regard in which he held US
      pediatrician Dr. Abraham Jacobi. Osler was not a saint, and he had his "rough
      side," but in his relationships with Jewish colleagues his example remains
      relevant.

PMID- 9176425
TI  - Harassment issues should be dealt with before they become problems.
AB  - Sexual and other forms of harassment are common in the medical work environment.
      Physicians who are employers and medical educators as well as clinicians should
      be aware they may be held responsible for the harassing conduct of colleagues,
      employees and others unless measures are in place in the workplace that show
      reasonable efforts have been made to prevent the behaviour and deal with it
      appropriately when it occurs. This article uses a US case to illustrate the
      evolution of a sexual-harassment complaint over several years.

PMID- 9176424
TI  - Helicobacter pylori: new developments and treatments.
AB  - The authors highlight new developments in research on Helicobacter pylori. There
      is now consensus that all patients with newly diagnosed or recurrent duodenal or
      gastric ulcers who have a positive test result for H. pylori should be treated
      for the infection. Patients presenting with complications of ulcers, such as
      bleeding, should also be treated. H. pylori has recently been classified as a
      definite human carcinogen by the International Agency for Research on Cancer. In
      treatment, new combination regimens, consisting of 3 or 4 different drugs, cure
      the infection in more than 80% of patients. Currently, the best combinations are:
      (1) omeprazole (or another proton-pump inhibitor), clarithromycin and
      metronidazole, (2) omeprazole (or another proton-pump inhibitor), clarithromycin
      and amoxicillin, (3) bismuth subsalicylate, tetracycline and metronidazole, and
      (4) omeprazole, bismuth subsalicylate, tetracycline and metronidazole.

PMID- 9176426
TI  - Preventing needle-stick injury.

PMID- 9176427
TI  - Medical recruitment in rural Canada: marathon breaks the cycle.
AB  - Two years ago, the 5500 residents of marathon, ont., had 1 overworked physician
      to look after their medical needs. Today, they have 7 physicians to share the
      load. In this article Michael OReilly looks at the steps the town took to attract
      new doctors. It offered a financial incentive and also worked to revitalize its
      hospital. As Marathon worked to attract new doctors, it also found that a new
      generation of physicians has much different career aspirations than past
      generations.

PMID- 9176428
TI  - Manitoba suicides force consideration of stresses facing medical residents.
AB  - The suicides of 3 Winnipeg medical residents within 15 months shocked Manitoba
      physicians and raised concerns among interns and residents across Canada. The
      cluster of self-inflicted deaths has observers wondering if the stress of
      residency programs was a contributing factor in the tragedies.

PMID- 9176429
TI  - MDs seen as key players in move to encourage active living in Canada.
AB  - Despite participACTION's preaching about the need to stay physically active, only
      a small percentage of Canadians exercise regularly at the level recommended for
      fitness. Nicole Baer discusses the issue with physicians and experts in the
      field, and also looks at American efforts to introduce Physician-based Assessment
      and Counselling for Exercise.

PMID- 9176430
TI  - Medical schools seeking new ways to cope with funding cutbacks.
AB  - Cuts in government funding mean that Canada's medical schools have to seek new
      ways to raise funds. Susan Thorne examines some of the ways faculties of medicine
      are coping with change. In the brave new world of medical education, schools are
      combining classes for medical students and other health professionals, seeking
      business alliances, encouraging attendance by full-tuition students from other
      countries and diversifying revenue bases through new programs, such as McGill's
      new 5-year MD-MBA degree.

PMID- 9176431
TI  - Will hospital closures mean physician unemployment in Ontario?
AB  - Dr. Duncan Sinclair, the former dean of medicine who heads the commission charged
      with restructuring Ontario's health care system, said something dramatic was
      needed to revamp the system. He wasn't kidding. His commission recently called
      for the closure of 3 hospitals in Ottawa and 10 more in Toronto. In a wideranging
      interview with Charlotte Gray he talks about the commission's goals and their
      potential impact on physicians.

PMID- 9176433
TI  - Online CME.

PMID- 9176432
TI  - Physicians debate Internet-related marital problems on CMA's online service.
AB  - The Internet itself has been the topic recently on the CMA's Internet-based
      discussion group for physicians, Clinical Q&A. A recent discussion involved
      physicians from around the country who have dealt with patients with marital
      problems related to the Internet. They concluded that the Internet may have made
      problems manifest, but the underlying issue--marital disharmony--already existed.

PMID- 9176434
TI  - Approaches for obtaining sperm in patients with male factor infertility.
AB  - OBJECTIVE: To describe methods of sperm retrieval for intracytoplasmic sperm
      injection (ICSI) in patients with male factor infertility and to review the
      clinical results using sperm from the different sources. DESIGN: The literature
      on sperm-obtaining methods and ICSI was reviewed. Studies related to this topic
      were identified through MEDLINE. RESULTS(S): This review describes the evolution
      of sperm retrieval methods. Sperm can be obtained by microepididymal sperm
      aspiration (MESA), percutaneous sperm aspiration (PESA), and testicular sperm
      extraction (TESE), from patients with congenital absence of the vas deferens or
      acquired vas obstruction. When ICSI is performed with ejaculated, epididymal, or
      testicular sperm, good fertilization and pregnancy rates are achieved without
      significant differences among the various sperm sources. The original
      percutaneous sperm aspiration method has been modified slightly and yields
      successful results. CONCLUSION(S): Viable pregnancies can be achieved with ICSI
      by using not only ejaculated sperm, but also epididymal and testicular sperm.
      Microepididymal sperm aspiration, percutaneous sperm aspiration, modified
      percutaneous sperm aspiration, and testicular sperm extraction can be considered
      standard procedures to treat male factor infertility.

PMID- 9176435
TI  - Worldwide frequency of a common genetic variant of luteinizing hormone: an
      international collaborative research. International Collaborative Research Group.
AB  - OBJECTIVE: To determine the worldwide frequency of a common immunological LH
      variant because of two point mutations in the LH beta-subunit gene (Trp8Arg and
      Ile15Thr). DESIGN: Cross-sectional study on LH status (variant and wild-type) in
      serum (or DNA) samples from Finland (Finns and Lapps), Estonia, Poland, Sweden,
      The Netherlands, United Kingdom, Italy, South Africa (blacks), Thailand, China,
      Japan, and the United States (Hispanics and blacks). SETTING: Academic research
      environment. PATIENT(S): Ambulatory adult men and women (n = 2,936) with minor
      illnesses and no known endocrinological disorders. INTERVENTION: A single blood
      sample was collected from each subject. MAIN OUTCOME MEASURE(S): The LH status
      was determined by two immunofluorometric assays using monoclonal antibodies. One
      (assay 1) only recognizes the wild-type LH, the other (assay 2) recognizes
      equally variant and wild-type LH. The ratio of assay 1 to assay 2 indicates the
      LH status: wild-type, > 0.9; heterozygote, 0.2 to 0.9; and homozygote, < 0.15.
      One population (Lapps) was studied by DNA analysis using polymerase chain
      reaction and allele-specific oligonucleotide hybridization. RESULT(S): The
      carrier frequency of the variant LH beta allele varied from 7.1% in U.S.
      Hispanics to 41.9% in Lapps of northern Finland. The variant LH beta allele
      tended to be more common in populations from Northern Europe as compared with
      those from Asia. CONCLUSION(S): The high frequency of the LH beta variant
      worldwide makes it an important confounding factor when obtaining
      disproportionately low LH levels with some immunometric assays. The LH variant
      may contribute to some pathologies of the pituitary-gonadal function.

PMID- 9176436
TI  - Infertility, fertility drugs, and invasive ovarian cancer: a case-control study.
AB  - OBJECTIVE: To assess the risk of invasive ovarian cancer among infertile women
      treated with fertility drugs. DESIGN: A case-control study. SETTING: Nationwide
      data based on public registers. PATIENT(S): All Danish women (below the age of 60
      years) with ovarian cancer during the period from 1989 to 1994 and twice the
      number of age-matched population controls. Included in the analysis were 684
      cases and 1,721 controls. MAIN OUTCOME MEASURE(S): Influence of parity,
      infertility, and fertility drugs on the risk of ovarian cancer after multivariate
      confounder control. Risk measure(s): odds ratios (OR) with 95% confidence
      intervals. RESULT(S): Nulliparous women had an increased risk of ovarian cancer
      compared with parous women: OR 1.5 to 2.0. Infertile, nontreated nulliparous
      women had an OR of 2.7 (1.3 to 5.5) compared with noninfertile nulliparous women.
      The OR of ovarian cancer among treated nulliparous women was 0.8 (0.4 to 2.0) and
      among treated parous 0.6 (0.2 to 1.3), compared with nontreated nulliparous and
      parous infertile women, respectively. CONCLUSION(S): Nulliparity implies a 1.5-
      to 2-fold increased risk of ovarian cancer. Infertility without medical treatment
      among these women increased the risk further. Among parous as well as nulliparous
      women, treatment with fertility drugs did not increase the ovarian cancer risk
      compared with nontreated infertile women.

PMID- 9176437
TI  - Retreatment with nafarelin for recurrent endometriosis symptoms: efficacy,
      safety, and bone mineral density.
AB  - OBJECTIVE: To assess the efficacy, safety, and effect on bone mineral density of
      a 3-month course of retreatment with intranasal nafarelin acetate for recurrent
      symptoms of endometriosis. DESIGN: Multicenter, open-label, nonrandomized
      clinical trial. SETTING: Eleven hospital-based and private practices. PATIENT(S):
      Thirty-six women with endometriosis symptoms recurring after 3 or 6 months of
      treatment with nafarelin. INTERVENTION(S): Nasal nafarelin 200 micrograms twice
      daily for 3 months. MAIN OUTCOME MEASURE(S): Assessments for dysmenorrhea,
      dyspareunia, pelvic pain, tenderness, and induration. Measurement of bone mineral
      density of the lumbar spine. RESULT(S): Improvements from admission to the end of
      retreatment were significant for dysmenorrhea, pelvic pain, tenderness,
      induration, and dyspareunia. Three months after retreatment ended, mean symptom
      scores for dysmenorrhea and pelvic tenderness, although worse than at the end of
      retreatment, were still significantly better than scores at admission. Mean bone
      mineral density 3 months after retreatment was 0.56% lower than before
      retreatment and 1.94% lower than before initial treatment. CONCLUSION(S): Three
      month nafarelin retreatment for recurrent endometriosis symptoms was effective
      and safe.

PMID- 9176438
TI  - Lignocaine aerosol spray in outpatient hysteroscopy: a randomized double-blind
      placebo-controlled trial.
AB  - OBJECTIVE: To assess the efficacy of lignocaine spray during outpatient
      hysteroscopy in reducing the need for additional anesthesia and reducing the
      discomfort of the procedure. DESIGN: A randomized double-blind, placebo
      controlled trial. SETTING: An undergraduate university teaching hospital in
      London. PATIENT(S): One hundred twenty patients undergoing outpatient
      hysteroscopy. INTERVENTION(S): Application of lignocaine spray to the cervix,
      cervical canal, and uterine cavity during outpatient hysteroscopy. MAIN OUTCOME
      MEASURE(S): The need to use additional anesthesia and the pain experienced at
      various steps of the procedure. RESULT(S): Women treated with active spray
      experienced significantly less pain when the cervix was grasped with a tenaculum
      at the start of hysteroscopy. There were no other significant differences in the
      outcome of hysteroscopy between the placebo and lignocaine groups, although there
      was a significant reduction in the use of additional anesthesia in both groups
      compared with historical controls. CONCLUSION(S): Lignocaine spray has beneficial
      effects on cervical but not uterine sensation. Pretreatment with either
      lignocaine or placebo seems to reduce the need for additional intracervical
      anesthesia during hysteroscopy.

PMID- 9176439
TI  - Women with functional hypothalamic amenorrhea but not other forms of anovulation
      display amplified cortisol concentrations.
AB  - OBJECTIVE: To test the hypothesis that increased cortisol secretion is specific
      to women with decreased GnRH drive and not found in eumenorrheic women or those
      with other causes of anovulation. DESIGN: Cortisol concentrations in blood were
      determined at 30-minute intervals for 24 hours in three well-characterized
      groups: women with functional hypothalamic amenorrhea, those with other causes of
      anovulation, and eumenorrheic women. SETTING: Academic medical center.
      PATIENT(S): Women aged 20 through 35 years, with well-defined reproductive
      states. INTERVENTION(S): Venous blood samples were obtained from, and
      psychometric inventories were completed by, the participants. MAIN OUTCOME
      MEASURE(S): Twenty-four-hour cortisol levels, 24-hour LH pulse patterns, and
      serial P levels were measured in women with functional hypothalamic amenorrhea,
      eumenorrheic women, and those with other causes of anovulation. RESULT(S):
      Cortisol secretion was higher in women with functional hypothalamic amenorrhea (n
      = 19) than in those with other causes of anovulation (n = 19) or eumenorrheic
      women (n = 19). Six women who recovered from functional hypothalamic amenorrhea
      had cortisol levels comparable to those of eumenorrheic women and those with
      other causes of anovulation. CONCLUSION(S): These data underscore the association
      between increased hypothalamic-pituitary-adrenal activity and reduced GnRH drive
      and support the concept that functional hypothalamic amenorrhea develops in
      response to stress-induced alterations in central neural function that modify
      hypothalamic function.

PMID- 9176440
TI  - The accuracy of serum chlamydial antibodies in the diagnosis of tubal pathology:
      a meta-analysis.
AB  - OBJECTIVE: To assess the discriminative capacity of Chlamydia antibody titers in
      the diagnosis of tubed pathology in subfertile patients. DESIGN: Meta-analysis of
      studies comparing Chlamydia antibody titers and laparoscopy for tubal patency and
      peritubal adhesions. PATIENTS: A total of 2,729 patients with subfertility in 23
      studies. INTERVENTION(S): Chlamydia antibody titer and laparoscopy as part of
      subfertility work-up. MAIN OUTCOME MEASURE: Sensitivity and specificity of
      Chlamydia antibody titers in the diagnosis of tubal pathology using laparoscopy
      with chromopertubation as the reference standard. RESULT(S): The discriminative
      capacity of Chlamydia antibody titers depended on the type of assay that was
      used. Summary receiver operating characteristic (ROC) curves of studies using
      ELISA or (micro)immunofluorescence revealed a better discrimination than the
      summary ROC-curve of studies using immunoperoxidase assay. CONCLUSION(S): The
      discriminative capacity of Chlamydia antibody titers by means of ELISA,
      microimmunofluorescence, or immunofluorescence in the diagnosis of any tubal
      pathology is comparable to that of hysterosalpingography (HSG) in the diagnosis
      of tubal occlusion. Chlamydia antibody testing involves little burden but
      provides no details on the anatomy of uterus and tubes. Whether or not Chlamydia
      antibody testing can replace HSG depends on the perspective taken in the
      diagnostic work-up of subfertility.

PMID- 9176441
TI  - Increased angiotensin II in ascites during severe ovarian hyperstimulation
      syndrome: role of early pregnancy and ovarian gonadotropin stimulation.
AB  - OBJECTIVE: To investigate the implications of the ovarian renin-angiotensin
      system (RAS) in the pathophysiology of the ovarian hyperstimulation syndrome
      (OHSS) in relation to gonadotropin stimulation and early pregnancy. DESIGN: A
      controlled clinical study comparing blood and simultaneously sampled peritoneal
      fluid (PF) from patients with severe OHSS and from controls without OHSS.
      SETTING: University Hospitals. PATIENT(S): Eleven patients with severe OHSS, 8
      patients with ascites of other origin, 9 patients with a first-trimester
      pregnancy, and 15 patients stimulated with gonadotropins for IVF. MAIN OUTCOME
      MEASURE(S): Angiotensin II immunoreactivity was measured in blood and PF and
      analyzed by high-performance liquid chromatography (HPLC) in ascites from OHSS.
      RESULT(S): Angiotensin II immunoreactivity (pg/mL; mean +/- SE) was highest in
      the ascites from pregnant OHSS (1,669 +/- 418), reaching levels 5 times higher
      than in the plasma (331 +/- 61) and 100 times higher than in control ascites (17
      +/- 6.7). Angiotensin II immunoreactivity was elevated in the PF during early
      pregnancy (211 +/- 68) and after gonadotropin stimulation (244 +/- 41) and was
      higher than in the plasma in both groups. Analysis by HPLC showed that the
      majority of Ang II immunoreactivity in the ascites of OHSS was because of true
      Ang II. CONCLUSION(S): Severe forms of OHSS, especially those associated with
      pregnancy, are consistently characterized by huge concentrations of Ang II
      immunoreactivity in the ascites, proved to be true Ang II by HPLC analysis. This
      may be due to the synergistic effects of exogenous and endogenous hCG on the
      ovarian RAS.

PMID- 9176443
TI  - Detection of immunoreactive interleukin-11 in human follicular fluid:
      correlations with ovarian steroid, insulin-like growth factor I levels, and
      follicular maturity.
AB  - OBJECTIVE: To prove the presence of interleukin-11 (IL-11) in the follicular
      fluid (FF), to determine its source and the correlation between IL-11 and
      fertilization outcome, follicular size, number of follicles per patient,
      steroids, and insulin-like growth factor-1 (IGF-I) levels. DESIGN: Interleukin-11
      levels were measured in FFs, aspirated during oocyte pickup for IVF. SETTING:
      Academic hospital and research environment. PATIENT(S): Follicular fluid and
      serum were obtained with informed consent from 44 patients undergoing IVF-ET.
      Granulosa cells were isolated from 17 patients. MAIN OUTCOME MEASURE(S): We
      hypothesized that IL-11 might play a role in follicular development, as do other
      related cytokines present in FF. Interleukin-11 was measured with ELISA.
      RESULT(S): Interleukin-11 was absent in the serum but present in FF and in
      conditioned medium from granulosa cells. Atretic follicles had higher
      concentrations of IL-11. No correlation was found between IL-11 and fertilization
      outcome, follicular size, steroid, IGF-I, and total protein concentrations.
      CONCLUSION(S): We conclude that IL-11 is present in FF. The role of IL-11 in
      follicular development should be the object of further investigations.

PMID- 9176442
TI  - Effect of two antiprogestins (mifepristone and onapristone) on endometrial
      factors of potential importance for implantation.
AB  - OBJECTIVE: To investigate the effects of postovulatory administration of
      antiprogestins on endometrial factors that may be of importance for successful
      implantation. DESIGN: Ten women were given 200 mg mifepristone and an additional
      10 women 400 mg of onapristone 48 hours after the LH surge in urine (LH + 2).
      MAIN OUTCOME MEASURE(S): Biopsies were assessed for histologic dating and the
      immunolocalization of [1] leukemia inhibitory factor, [2] 15-hydroxyprostaglandin
      dehydrogenase, and [3] the cell proliferation marker Ki 67. Hormonal measurements
      in blood and urine were used to monitor the effects on the ovarian cycle.
      Glycodelin (placental protein 14) concentrations were measured in blood taken on
      LH + 12. RESULT(S): Treatment with antiprogestins retarded the development of
      secretory changes without affecting the length of the luteal phase. In addition,
      there was reduced immunostaining for 15-hydroxyprostaglandin dehydrogenase within
      glands and a significant reduction in serum levels of glycodelin. Reduced
      immunostaining for leukemia inhibitory factor also was apparent within glands in
      biopsies taken on LH + 6 of the treatment cycle. Increased Ki 67 immunostaining
      was observed on both cycle days after treatment, consistent with P antagonism.
      CONCLUSION(S): Administration of mifepristone and onapristone adversely affects
      uterine receptivity. This adds further evidence to support their potential as a
      method of postovulatory fertility control.

PMID- 9176444
TI  - Enhanced interleukin-4 expression in patients with endometriosis.
AB  - OBJECTIVE: To investigate the expression of cytokines by T-helper cells type 1
      (interleukin [IL]-2 and interferon-gamma [IFN-gamma]) and type 2 (IL-4 and IL-10)
      in peripheral blood monocytes and peritoneal fluid (PF) cells from patients with
      endometriosis. DESIGN: Peripheral blood (PB) monocytes and PF cells from patients
      with endometriosis were isolated and the expression of cytokines investigated.
      SETTING: Institute for the treatment of endometriosis and research institute in
      university-based medical center. PATIENT(S): The study included 7 women with
      normal pelvic structure, 36 patients with endometriosis, and 7 women with pelvic
      adhesion but without apparent endometriotic lesion. The existence and severity of
      endometriosis was determined by laparoscopic examination. INTERVENTION(S): All
      patients received laparoscopic operation to identify the existence and stages of
      endometriosis. Danazol (200 mg, twice daily) was prescribed for those with
      endometriosis. MAIN OUTCOME MEASURE(S): Transcription of cytokines were directly
      analyzed using the reverse transcriptase-polymerase chain reaction method. The
      concentrations of cytokines in peritoneal fluids and sera were analyzed by the
      ELISA. RESULT(S): Levels of IL-4 messenger RNA (mRNA) and protein in the PB and
      peritoneal cells of patients with endometriosis were higher than those of normal
      patients, whereas levels of IFN-gamma mRNA and protein were suppressed. There
      were no significant changes in the mRNA or protein levels of IL-2 or IL-10 in
      both peritoneal fluids and sera. The level of IL-4 was reduced to normal after
      combined treatment with laparoscopic surgery and danazol. The secretion of IFN
      gamma was elevated after treatment. CONCLUSION(S): Cytokine secretion by T-helper
      cells type 1 and type 2 is altered in women with endometriosis, suggesting that
      these T-helper subsets play a role in the immunologic responses to endometriosis.

PMID- 9176445
TI  - Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with
      endometriosis and its modulation of expression in mesothelial cells.
AB  - OBJECTIVE: To investigate monocyte chemotactic protein-1 concentrations in the
      peritoneal fluid (PF) of women with or without endometriosis, then assess
      peritoneal mesothelial cells as a potential source of monocyte chemotactic
      protein-1. DESIGN: Prospective study. SETTING: University medical center.
      PATIENT(S): Women with (n = 60) or without (n = 18) endometriosis.
      INTERVENTION(S): First monocyte chemotactic protein-1 levels in PF were measured,
      then mesothelial cells in culture were treated with cytokines. MAIN OUTCOME
      MEASURE(S): In PF and culture supernatants, monocyte chemotactic protein-1 was
      measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA
      expression was evaluated by Northern analysis. RESULT(S): The median
      concentration of monocyte chemotactic protein-1 in PF of control women was 137
      pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of
      women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and
      that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL).
      Within the moderate to severe endometriosis group, monocyte chemotactic protein-1
      levels were higher in women with untreated endometriosis (354 pg/mL range 0 to
      6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216
      pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher
      in the proliferative phase than in the secretory phase. Mesothelial cells
      produced constitutively monocyte chemotactic protein-1; moreover, both
      interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of
      monocyte chemotactic protein-1. CONCLUSION(S): Levels of monocyte chemotactic
      protein-1 in PF were higher during the proliferative phase than secretory phase
      of control women and increased in moderate to severe endometriosis. The regulated
      expression of monocyte chemotactic protein-1 may recruit macrophages into PF and
      contribute to the pathogenesis of endometriosis.

PMID- 9176446
TI  - Comparison of transmyometrial and transcervical embryo transfer in patients with
      previously failed in vitro fertilization-embryo transfer cycles and/or cervical
      stenosis.
AB  - OBJECTIVE: To compare ultrasound-guided transmyometrial and transcervical ET in
      patients with cervical stenosis or in patients who failed to conceive after at
      least three previous IVF-ET cycles. DESIGN: A prospective, randomized study.
      SETTING: The IVF-ET Unit at Serlin Maternity Hospital. PATIENT(S): Forty patients
      undergoing IVF-ET. INTERVENTION(S): Ultrasound-guided transvaginal,
      transmyometrial, versus transcervical ET. MAIN OUTCOME MEASURE(S): Clinical
      pregnancy rate. RESULT(S): Transmyometrial ET was performed in 20 patients and
      resulted in one clinical pregnancy. Transcervical ET, performed in another 20
      similar patients, resulted in three clinical pregnancies. CONCLUSION(S): No
      benefit was derived by electing transmyometrial ET in preference to transcervical
      ET in patients who had failed to conceive in previous cycles.

PMID- 9176447
TI  - Is the obstetric outcome of in vitro fertilized singleton gestations different
      from natural ones? A controlled study.
AB  - OBJECTIVE: To determine whether singleton IVF pregnancies carry adverse maternal
      or fetal outcome when compared with naturally conceived gestations. DESIGN: An
      analysis of the obstetric outcome of singleton IVF pregnancies in comparison with
      matched, naturally conceived singleton controls. SETTING: In vitro fertilization
      unit and obstetric service at a tertiary medical center. PATIENT(S): Two hundred
      sixty consecutive singleton IVF pregnancies and 260 naturally conceived singleton
      controls matched 1:1 for maternal age, parity, ethnic origin, and location and
      date of delivery. INTERVENTION(S): In vitro fertilization-ET. MAIN OUTCOME
      MEASURE(S): The rate of antenatal obstetric complications, nonvertex
      presentation, cesarean section, preterm labor, low birth weight, small and very
      small for gestational age, neonatal intensive care unit admissions, and perinatal
      mortality. RESULT(S): The rates of most antenatal complications were similar in
      both groups. Urinary tract infection was the only complication diagnosed
      significantly more frequently after IVF (7.3% versus 1.2%); however, the rates of
      severe urinary tract infection necessitating hospitalization were similar. The
      incidence of nonvertex presentation was also similar. The cesarean section rate
      was significantly higher among IVF patients (41.9% versus 15.5%). The rates of
      preterm labor, low birth weight, small and very small for gestational age,
      neonatal intensive care unit admissions, and perinatal mortality were comparable.
      CONCLUSION(S): When controlling for maternal age, parity, ethnic origin, and
      location and date of delivery, singleton IVF pregnancies do not carry an
      increased risk for prematurity, low birth weight, or maternal or fetal
      complications. Still, these pregnancies are associated with a high rate of
      cesarean sections.

PMID- 9176448
TI  - Antiphospholipid antibodies and pregnancy rates and outcome in in vitro
      fertilization patients.
AB  - OBJECTIVE: To determine the relationship between antiphospholipid antibodies and
      pregnancy rates (PRs) and outcome among IVF patients. DESIGN: Prospective
      collection of all serum samples with assays for immunoglobulin G (IgG), IgA, and
      IgM antibodies for anticardiolipin, antiphosphatidyl serine, antiphosphatidyl
      ethanolamine, antiphosphatidyl choline, antiphosphatidyl inositol,
      antiphosphatidyl glycerol, and antiphosphatidic acid being done following
      completion of all treatment cycles. SETTING: A tertiary care teaching hospital.
      PATIENT(S): Seven hundred ninety-three patients attempting to conceive through
      IVF. MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) and pregnancy loss rates
      relative to each of the various antiphospholipid antibodies that were measured.
      RESULT(S): There were 528 pregnancies for an overall PR of 66%. Pregnancy rates
      were equal among patients with positive and negative antiphospholipid antibodies
      for each of the 21 measured antibodies. Use of receiver operator characteristic
      curves and logistic regression further confirmed that there was no relationship
      between PRs or outcome based on antiphospholipid antibodies for any definable
      threshold value. CONCLUSION(S): Elevated antiphospholipid antibody levels are not
      associated with any change in PRs or pregnancy loss rates in patients attempting
      to conceive through IVF.

PMID- 9176449
TI  - Pregnancy and birth after intracytoplasmic sperm injection with totally immotile
      sperm recovered from the ejaculate.
AB  - OBJECTIVE: To report the birth of two healthy children after intracytoplasmic
      sperm injection (ICSI) with totally immotile spermatozoa recovered from the
      ejaculate. DESIGN: Retrospective case report. SETTING: University-based hospital.
      PATIENT(S): Four couples in whom spermatozoa recovered from the ejaculate were
      totally immotile but presented normal vitality scores. INTERVENTION(S):
      Therapeutical IVF-ET attempts coupled with ICSI. MAIN OUTCOME MEASURE(S):
      Fertilization and pregnancy results after ICSI. RESULTS: With random sperm
      injection, 19 of the 36 injected oocytes showed normal fertilization and
      cleavage. One of four patients had a twin pregnancy that resulted in birth of two
      healthy children. CONCLUSION(S): In cases in which totally immotile ejaculated
      sperm present normal vitality scores, normal clinical outcomes can be achieved by
      using the usual random sperm selection during conventional ICSI.

PMID- 9176450
TI  - Absence of block to polyspermy at the human oolemma.
AB  - OBJECTIVE: To study the fusiogenic ability of human spermatozoa and oocytes.
      DESIGN: Retrospective study of 3,027 oocytes included in a program of subzonal
      insemination (SUZI). SETTING: Assisted fertilization program in an academic
      research environment. PATIENT(S): Couples with characterized male factor
      infertility or previous unexplained IVF failures. INTERVENTION(S): Subzonal
      insemination (SUZI) was performed after study of the sperm pathology. The number
      of microinjected spermatozoa was controlled. MAIN OUTCOME MEASURE(S):
      Fertilization and polyspermia rates were analyzed according to the number of
      microinjected spermatozoa and to the indication of SUZI. RESULT(S): The
      fertilization rate increased linearly between one and three microinjected
      spermatozoa. Above this number, the rate plateaued around 25%. Polyspermia was
      correlated with the number of microinjected spermatozoa (r = 0.97). The
      fusiogenic ability of motile sperm cells was dependent on the semen
      characteristics and the sperm pathology. Observed diploid and polyspermia rates
      did not differ from the calculated probability of microinjecting only one or at
      least one fertilizing spermatozoon into the perivitelline space, respectively.
      CONCLUSION(S): Data support the hypothesis that a physiologic block at the human
      oolemma is absent. The post-SUZI fertilization rate also can be explained by the
      probability of finding one fertilizing spermatozoon among those that were
      microinjected and by the limited number of sperm heads allowed to decondense in
      the ooplasm.

PMID- 9176451
TI  - A meta-analysis of 61 sperm count studies revisited.
AB  - OBJECTIVE: To re-examine data on sperm counts over time from 61 studies from
      around the world. DESIGN: Parametric analyses and flexible nonlinear models of
      the relation between sperm counts and time. MAIN OUTCOME MEASURE(S): Mean sperm
      concentrations per milliliter and regression coefficients for possible trends of
      concentrations over time. RESULT(S): A significant decline was found only in U.S.
      studies. CONCLUSION(S): Studies from specific sites have found declines in sperm
      counts, but a world-wide decline has not been demonstrated. Rigorous assessment
      of statistical models should be done before conclusions are drawn. Flexible
      smoothing models are a useful addition to currently available analytic methods.

PMID- 9176452
TI  - Failure of multitube sperm swim-up for sex preselection.
AB  - OBJECTIVE: To use double-label fluorescence in situ hybridization to evaluate a
      modified swim-up procedure that is purported to be effective for preconceptual
      sex selection. DESIGN: Controlled, blinded study. SETTING: University hospital
      laboratories. PATIENT(S): Donor males reporting for routine semen analysis. MAIN
      OUTCOME MEASURE(S): Percentages of X- and Y-bearing spermatozoa in neat semen and
      in two swim-up fractions, determined using double-label fluorescence in situ
      hybridization. RESULT(S): No clinically significant change from a 1:1 ratio was
      found in the distribution of X- or Y-bearing spermatozoa after double-label
      fluorescence in situ hybridization following a modified swim-up procedure and
      irrespective of the time (15, 30, 45, and 60 minutes) allowed for swim-up.
      CONCLUSION(S): Using fluorescence in situ hybridization, a modified swim-up
      procedure was evaluated for its purported ability to skew the relative
      percentages of X- and Y-bearing spermatozoa. No clinically significant change in
      the ratio of X- to Y-bearing spermatozoa was detected independent of time.
      Therefore, clinical application of this procedure should be strongly discouraged.

PMID- 9176453
TI  - Seminal reactive oxygen species and sperm motility and morphology in men with
      spinal cord injury.
AB  - OBJECTIVE: To assess the generation of reactive oxygen species and its relation
      to semen characteristics in men with spinal cord injury. DESIGN: Cross-sectional
      study. SETTING: Andrology laboratory at a tertiary care facility and research
      laboratory at a major medical center. PATIENT(S): Men with spinal cord injury and
      normal men. INTERVENTION(S): Collecting ejaculates from men with spinal cord
      injury by electroejaculation and vibratory stimulation and from normal men by
      masturbation. MAIN OUTCOME MEASURE(S): Measurement of reactive oxygen species
      before and after stimulation with 50 microM N-formyl-methionyl
      leucylphenylalanine (FMLP) and 100 nM 12-myristate 13-acetate phorbol ester
      (PMA), white blood cell (WBC) concentration, sperm motility and morphology, and
      ejaculation method. RESULT(S): Compared with controls, levels of reactive oxygen
      species in men with spinal cord injury were significantly higher in unstimulated,
      f-MLP-stimulated, and PMA-stimulated specimens. The WBC concentration was
      significantly elevated in patients with spinal cord injury. Sperm motility in men
      with spinal cord injury was inversely related to the level of reactive oxygen
      species. The percentage of morphologically normal spermatozoa was significantly
      lower in men with spinal cord injury. Levels of seminal reactive oxygen species
      did not differ when comparing specimen type (antegrade versus retrograde) or
      method of ejaculation in men with spinal cord injury. CONCLUSION(S): Men with
      spinal cord injury had elevated levels of reactive oxygen species in their semen.
      Levels of reactive oxygen species were negatively correlated with sperm motility.
      Levels of reactive oxygen species were independent of the method of ejaculation
      or the type of specimen.

PMID- 9176455
TI  - Interference of antisperm antibodies with the induction of the acrosome reaction
      by zona pellucida (ZP) and its relationship with the inhibition of ZP binding.
AB  - OBJECTIVE: To determine whether antisperm antibodies can interfere with the
      induction of the acrosome reaction (AR) by the zona pellucida (ZP) and whether
      this interference also can occur in the absence of an inhibitory effect on ZP
      binding. DESIGN: Prospective in vitro study. SETTING: A tertiary care center, the
      Andrologic Clinic, University of L'Aquila. PATIENT(S): Sera from 12 infertile
      patients with high titers of circulating antibodies directed against the sperm
      head were studied. INTERVENTION: None MAIN OUTCOME MEASURE(S): The effect of
      antisperm antibodies on ZP binding was evaluated by matching antibody-exposed and
      nonexposed donor sperm suspensions labeled with fluorescein or rhodamine,
      respectively, and incubated with the same salt-stored human ZPs. The effect of
      antibodies on ZP-induced AR was determined by challenging antibody-exposed and
      nonexposed donor sperm suspensions with human ZPs disaggregated with acidic
      NaH2PO4. Acrosomal status was evaluated using fluorescein-labeled Pisum sativum
      agglutinin and supravital stain Hoechst 33258. In some selected cases, the effect
      of antisperm antibodies on the acrosomal status of sperm bound to intact ZP also
      was evaluated using transmission electron microscopy. RESULT(S): Five of 12 sera
      exhibited an inhibitory effect on ZP binding. An inhibition of AR induction by
      disaggregated ZPs (ranging from 64% to 98%) was produced by all 5 sera with an
      inhibitory effect on ZP binding and by 2 of 7 sera without an inhibitory effect
      on ZP binding. The different effects of antisperm antibodies on AR induction by
      disaggregated ZP were confirmed by comparing with ultrastructural evaluations on
      the acrosomal status of sperm bound to intact ZP. CONCLUSION(S): Antisperm
      antibodies can interfere with the induction of AR by ZP. This inhibition can
      occur even in the absence of an inhibitory effect on ZP binding. Neither effect
      may occur.

PMID- 9176454
TI  - Clinical significance of human sperm-zona pellucida binding.
AB  - OBJECTIVE: To assess the relationship between sperm morphology and motion
      parameters and sperm-zona pellucida (ZP) binding capacity under hemizona assay
      (HZA) conditions and to determine the discriminatory power of the HZA for the
      prediction of in vitro sperm fertilizing ability. DESIGN: Prospectively designed
      study. SETTING: Academic tertiary centers. PATIENT(S): One hundred ninety-six
      couples undergoing IVF therapy participated in this study. INTERVENTION(S):
      Hemizona assay and IVF results were determined for each couple. MAIN OUTCOME
      MEASURE(S): Computerized sperm motion analysis, sperm morphology (strict)
      criteria), and HZA results were correlated with fertilization outcome. RESULT(S):
      Among sperm parameters from the original ejaculates, morphology was the best
      predictor of sperm-ZP binding ability; hyperactivated motility was the best
      predictor of HZA results after swim-up separation of the motile sperm fractions.
      The HZA index provided the highest discriminatory power for fertilization
      success/failure, with an overall accuracy of 86%. CONCLUSION(S): Sperm morphology
      and hyperactivated motility showed a high correlation with the capacity of sperm
      to achieve tight binding to the ZP. The excellent positive and negative
      predictive values of the HZA for fertilization outcome provide additional support
      for the use of this functional bioassay in the decision-making process within the
      assisted reproduction setting.

PMID- 9176456
TI  - Estimation of aneuploidy levels for 8, 15, 18, X and Y chromosomes in 97 human
      sperm samples using fluorescence in situ hybridization.
AB  - OBJECTIVE: To estimate the mean frequency of aneuploidy levels of chromosomes 8,
      15, 18, X, and Y in human sperm, while minimizing the effect of individual
      factors by analyzing sperm samples from a large set of patients. DESIGN:
      Prospective randomized analysis of sperm nuclei by fluorescence in situ
      hybridization. SETTING: University-based laboratory for reproductive biology.
      PATIENT(S): One hundred two patients with a large distribution of sperm
      parameters, randomly selected from volunteers who had presented seeking a semen
      analysis. INTERVENTION(S): The sperm samples were prepared for fluorescence in
      situ hybridization. MAIN OUTCOME MEASURE(S): The disomy frequencies for
      chromosomes 8, 15, 18, and sex chromosomes were determined using fluorescence in
      situ hybridization. RESULT(S): The mean frequencies of disomy for autosomes were
      0.18% for chromosome 8, 0.06% for chromosome 15, 0.2% for chromosome 18, and
      0.24% for gonosomes (XX, 0.04%; YY, 0.05%; XY, 0.15%). CONCLUSION(S): This study
      confirms other previous evaluations on restricted numbers of patients. Our
      results seem to confirm a relative equiprobability of disomy frequencies
      concerning the different chromosomal pairs during male meiosis.

PMID- 9176457
TI  - The effect of 12-myristate 13-acetate phorbol ester on human sperm
      hyperactivation.
AB  - OBJECTIVE: To determine whether 12-myristate 13-acetate phorbol ester (PMA) can
      increase hyperactivated motility of human sperm. DESIGN: A controlled
      pharmacological study using computer-assisted semen analysis. SETTING: Andrology
      laboratory in a medical research institution. PATIENT(S): Normal semen was
      obtained from 48 men. INTERVENTION(S): Washed sperm were exposed to different
      concentrations of PMA alone or with P and pentoxifylline (PTX) for up to 2 hours
      and sperm motility measured by a computer-assisted semen analyzer. MAIN OUTCOME
      MEASURE(S): The percentage of sperm with hyperactivated motility was determined
      from the motility parameters: curvilinear velocity, linearity, and maximum
      amplitude of lateral head displacement. RESULT(S): Phorbol ester PMA increased
      hyperactivated motility in a dose- and time-dependent manner. At 1 hour, the
      average increases in hyperactivated motility were as follows: 2 microM, 4.8% +/-
      1.5%; 6 microM, 9.6% +/- 1.5%; and 20 microM, 11.3% +/- 2.2%. The PMA effect was
      not altered when P or PTX were added although each separately had a positive
      effect on hyperactivation. CONCLUSION(S): Phorbol ester PMA stimulates human
      sperm hyperactivated motility, indicating the involvement of protein kinase C in
      the signal transduction pathway.

PMID- 9176458
TI  - Antibiotics: effect on cryopreserved-thawed human sperm motility in vitro.
AB  - OBJECTIVE: To analyze the motility and fertilizing capacity of sperm treated with
      different antibiotics. DESIGN: Prospective comparative study. SETTING: Clinical
      and academic research environment. PATIENT(S): Pooled cryopreserved donor sperm
      (n = 14). INTERVENTION(S): Sperm were washed with Percoll and resuspended in
      HEPES-buffered human tubal fluid medium containing either amoxicillin, ofloxacin,
      ciprofloxacin hydrochloride, nitrofurantoin monohydrate, doxycycline hyclate,
      cefuroxime axetil, or control medium. MAIN OUTCOME MEASURE(S): Sperm kinematic
      and fertilizing parameters. RESULT(S): Sperm hyperactivation was decreased in
      physiologic concentrations of ciprofloxacin hydrochloride and doxycycline hyclate
      over the course of 48 hours. At pharmacologic concentrations, ciprofloxacin
      hydrochloride, cefuroxime axetil, and nitrofurantoin monohydrate adversely
      affected motility with decreased rapid progression. Cessation of motility
      occurred in cefuroxime axetil and nitrofurantoin monohydrate. Sperm
      hyperactivation was also absent. Cefuroxime axetil decreased the percentage of
      intact acrosomes. In contrast, physiologic doses of ciprofloxacin hydrochloride
      or ofloxacin enhanced sperm fertilizing capacity. CONCLUSION(S): Ciprofloxacin
      affected hyperactivation by altering membrane properties, whereas doxycycline
      inhibited the capacitation process. Cessation of motility in cefuroxime axetil
      was linked to disrupted sperm head membranes. Sperm motility and fertilizing
      capacity were decreased in nitrofurantoin because of decreased metabolism. The
      positive effect of ofloxacin on fertilizing capacity did not involve changes in
      acrosome.

PMID- 9176459
TI  - The effect of human papillomavirus infection on sperm cell motility.
AB  - OBJECTIVE: To investigate the presence of human papillomavirus (HPV) in human
      sperm cells and to evaluate potential effects of HPV on the sperm functions.
      DESIGN: A descriptive clinical study. PATIENT(S): Specimens of semen were
      collected from 24 randomly selected patients who attended the fertility clinics
      at Chang Gung Memorial Hospital. MAIN OUTCOME MEASURE(S): The presence of HPV DNA
      and RNA were examined by polymerase chain reaction. Semen quality and sperm cell
      function were analyzed by computer-aided autoanalyzer. RESULT(S): Human
      papillomavirus type 16 DNA and RNA were found in 6 (25%) and 2 (8%) of the sperm
      cells specimens, respectively. Human papillomavirus type 18 DNA and RNA were
      present in 11 (46%) and 5 (21%) of the same sperm cells specimens, respectively.
      Incidence of asthenozoospermia among patients infected with either HPV was
      significantly higher than in those without HPV in their sperm cells (75% versus
      8%). Although performance of curvilinear velocity, straight-line velocity, and
      mean amplitude of lateral head displacement was significantly lower in HPV
      infected specimens, the differences of linearity, beat cross frequency, and
      straightness were not statistically significant. CONCLUSION(S): These results
      suggest that human papillomavirus can be found in human sperm cells and that
      certain HPV-specific genes are actively transcribed. Sperm motility parameters
      seem to be affected by the presence of HPV in the sperm cells, and also the
      incidence of asthenozoospermia may be associated with HPV infection.

PMID- 9176462
TI  - Psychological consequences of having triplets: a 4-year follow-up study.
AB  - OBJECTIVE: To assess the mental health of mothers of triplets and the quality of
      relationship with the children 4 years after delivery. DESIGN: Prospective follow
      up study from delivery, to 4 years. Assessments at home by a psychologist, using
      semistructured tape-recorded interviews. SETTING: One maternity hospital in
      Paris, France. PATIENT(S): Eleven consecutive mothers having delivered triplets
      between October 1988 and February 1990. All except one had conceived after
      infertility treatment. MAIN OUTCOME MEASURE(S): Evaluation of the mothers'
      emotional well-being and level of depression measured by the CES-D Scale (Center
      for Epidemiologic Studies-Depression Scale). Opinion of the mothers about the
      quality of the relationship with the children. RESULT(S): All mothers reported
      emotional distress at 4 years, mainly fatigue and stress. Four mothers had a high
      score of depression and used psychotropic medication. The relationship with the
      children and difficulties in coping with their aggressive behavior and conflicts
      were the main reason for psychological distress. Difficulties had not decreased
      since the previous assessment at 2 years. Four mothers spontaneously expressed
      regrets about having triplets. CONCLUSION(S): Patients undergoing infertility
      treatments should receive adequate information about the long-term psychological
      "cost" of a triplet birth. Infertility treatments should be adapted in order to
      decrease the risk of triplet pregnancies.

PMID- 9176460
TI  - A technique for standardization and quality control of subjective sperm motility
      assessments in semen analysis.
AB  - OBJECTIVE: To establish a quality control method to monitor and eventually to
      standardize the subjective assessment of sperm motility in conventional semen
      analysis. DESIGN: Quality control study running over 2 years. SETTING: University
      infertility clinic and andrology laboratory. PATIENT(S): Randomly chosen patients
      attending the clinic. MAIN OUTCOME MEASURE(S): Conventional semen analysis with
      sperm motility assessed by grading according to the World Health Organization
      (WHO) criteria and analysis of individual sperm tracks with a computer-aided
      sperm analysis (CASA) system. Formulas were established to identify, from the
      track data, the threshold velocity values for distinguishing between motility
      grades a and b and motility grades b and c for each technician. RESULT(S): The
      subjective thresholds above which technicians categorized sperm as WHO grades a
      and b were determined by CASA to be 61 +/- 1 and 11 +/- 1 micron/s (straight-line
      velocity), respectively. Agreement among three to five technicians over 2 years
      was reasonable (coefficient of variation < 20%), but threshold values were
      variable. CONCLUSION(S): Agreement within and between laboratories in the
      assessment of sperm motility grades could be achieved by agreeing on designated
      values for threshold velocities for grade a and b sperm. On the basis of such
      values, CASA analysis could be used to provide the expected percentages of grades
      a, b, and c forms for quality control samples recorded and distributed on
      videotapes, against which technicians could adjust their subjective assessments.

PMID- 9176461
TI  - Indisputable double paternity in dizygous twins.
AB  - OBJECTIVE: To report a case of heteropaternal superfecundation. DESIGN: Case
      report. SETTING: University paternity laboratory. PATIENT(S): Father, mother, and
      a set of twins. INTERVENTION(S): Blood typing conventional markers, as well as
      polymerase chain reaction loci and restriction fragment length polymorphism loci
      of DNA. MAIN OUTCOME MEASURE(S): Heteropaternal superfecundation was demonstrated
      after paternity investigation. RESULT(S): The probability of paternity for twin 1
      was 99.9999998%, whereas that for twin 2 was excluded on the basis of the
      following tests: Fy, Pi, human leukocyte antigen (HLA)-DQA1, D1S80, D17S5, HBGG,
      D5S110, D2S44, and D10S28. CONCLUSION(S): Dizygous twins can have different
      biologic fathers, as demonstrated in this case. According to published data, the
      frequency of twins with different fathers is probably underestimated, at least in
      small selected populations such as those of paternity suits.

PMID- 9176463
TI  - A prospective randomized comparison between long and discontinuous-long protocols
      of gonadotropin-releasing hormone agonist for in vitro fertilization.
AB  - OBJECTIVE: To investigate the efficacy of a discontinuous-long protocol in an IVF
      program. DESIGN: Prospective randomized study. SETTING: University hospital.
      PATIENT(S): One hundred thirty-seven IVF cycles of 92 patients in an outpatient
      IVF program from April 1995 to December 1995. INTERVENTION(S): In the
      discontinuous-long protocol group (n = 68), GnRH agonist (GnRH-a) was
      administered from the luteal phase until cycle day 7, when pure FSH
      administration was begun. In the long protocol group (n = 69), GnRH-a was
      administered until the day before hCG administration. MAIN OUTCOME MEASURE(S):
      Serum LH and ovarian steroid hormone levels, and IVF outcome. RESULT(S): The
      period and the total dosage of hMG were increased in the discontinuous-long
      protocol group. Although the fertilization rate was similar under both protocols,
      the number of embryos transferred was smaller and the cancellation rate was
      higher in the discontinuous-long protocol group because of the greater failure of
      oocyte retrieval and fertilization. Serum E2 levels in the late follicular phase
      were lower in the discontinuous-long protocol group. CONCLUSION(S): Early
      discontinuation of GnRH-a is not beneficial because of its adverse effects on
      follicular development.

PMID- 9176464
TI  - The use of methotrexate and arterial embolization to avoid surgery in a case of
      cervical pregnancy.
AB  - OBJECTIVE: To describe the management of a case of cervical ectopic pregnancy
      (EP) DESIGN: Case report. SETTING: University-affiliated teaching hospital.
      PATIENT(S): A 26-year-old woman, gravida 4, para 0-1-2-0 with the diagnosis of a
      cervical EP. INTERVENTION(S): Systemic methotrexate (MTX) and arterial
      embolization. RESULT(S): A cervical EP was diagnosed by ultrasonography. The
      patient was treated with systemic MTX. Vaginal bleeding began 4 days later and
      was treated with arterial embolization, thus eliminating the need for surgical
      intervention. The pregnancy resolved and the patient has resumed normal
      menstruation and again is attempting pregnancy. CONCLUSION(S): Arterial
      embolization can be used to avoid surgical intervention in cases of cervical EP
      in which hemorrhage occurs after treatment with chemotherapy.

PMID- 9176465
TI  - Successful pregnancies with the use of laminaria tents before embryo transfer for
      refractory cervical stenosis.
AB  - OBJECTIVE: To determine whether laminaria tents are a safe and effective method
      of cervical dilatation in patients with a history of cervical stenosis and
      difficult ET. DESIGN: Case reports describing two patients. SETTING: Tertiary
      care, assisted reproduction practice. PATIENT(S): Two patients with cervical
      stenosis and a history of multiple failed cycles of IVF. INTERVENTION(S):
      Laminaria tents were placed intracervically before ET. MAIN OUTCOME MEASURE(S):
      Presence of a gestational sac and fetal heartbeat on ultrasound. RESULT(S):
      Successful clinical pregnancies occurred in both patients after laminaria
      placement and ET. CONCLUSION(S): Laminaria tent cervical dilatation appears to be
      a safe and effective option to assist ET in patients with a history of cervical
      stenosis.

PMID- 9176467
TI  - Reply to the reply on IUI.

PMID- 9176466
TI  - Births after transcervical gamete intrafallopian transfer with a falloposcopic
      delivery system.
AB  - OBJECTIVE: To evaluate the safety and efficiency of a new delivery system to
      perform transcervical GIFT. DESIGN: Evaluation of pregnancy rate (PR),
      miscarriage rate, ectopic pregnancy rate, and delivery rate. SETTING: Institute
      of Obstetrics and Gynecology, Reproductive Endocrinology Unit, Infertility and
      IVF Center. PATIENT(S): Twenty-five patients with patent tubes documented by
      laparoscopy plus falloposcopy. INTERVENTION(S): Superovulation was induced with
      GnRH analogue and FSH. Under laparoscopic control, transcervical cannulation of
      the tube was done using a linear everting catheter incorporating direct
      falloposcopic vision of the tubal lumen. Two lengths of everting catheter (3 and
      6 cm) were used providing either isthmic-ampullary or midampullary placement of
      the inoculum. A comparison was done in terms of ease of access and transfer,
      falloposcopic observations, and PRs between the groups. MAIN OUTCOME MEASURE(S):
      Efficacy was established by evaluating the PR, miscarriage rate, ectopic
      pregnancy rate, and delivery rate. RESULT(S): The PR was 28% (with no differences
      between the lengths of everting catheters). No ectopic pregnancies occurred. The
      abortion rate was 28.6% and the delivery rate was 20%. Neither tubal perforation
      nor other complications occurred during the procedure. CONCLUSION(S):
      Falloposcopic GIFT is safe and efficient and may be a less invasive alternative
      than laparoscopic transfer.

PMID- 9176469
TI  - Noninvasive methods to obtain sperm.

PMID- 9176468
TI  - Cause for premature luteinization?

PMID- 9176470
TI  - Excessive use of a single donor? And inadvertent consanguinity.

PMID- 9176471
TI  - Subtotal hysterectomy in patients with endometriosis--an option?

PMID- 9176473
TI  - Money matters.

PMID- 9176472
TI  - Subtotal hysterectomy in patients with endometriosis--an option.

PMID- 9176475
TI  - Importance of anti-HIV-1 antibodies.

PMID- 9176474
TI  - Cyclosporin and the clinical investigator.

PMID- 9176476
TI  - Are leukotoxins toxic?

PMID- 9176477
TI  - p27 expression and gastric carcinoma.

PMID- 9176479
TI  - Tracing the brain's circuitry with functional imaging.

PMID- 9176478
TI  - Cardiovascular disease burden increases, NIH funding decreases.

PMID- 9176480
TI  - A stimulating treatment for emphysema.

PMID- 9176481
TI  - Fighting HIV-1 with IL-16.

PMID- 9176482
TI  - Progress of the smart bomb cancer virus.

PMID- 9176483
TI  - Motors, channels and the sounds of silence.

PMID- 9176485
TI  - Gene therapy: progress, problems, prospects.

PMID- 9176484
TI  - Cytotrophoblasts: masters of disguise.

PMID- 9176486
TI  - The proto-oncogene Bcl-2 and its role in regulating apoptosis.

PMID- 9176487
TI  - Detection of bladder cancer recurrence by microsatellite analysis of urine.
AB  - A reliable, noninvasive method for monitoring patients with transitional cell
      carcinoma (TCC) of the bladder would be of great clinical benefit. Cystoscopy is
      currently the "gold standard," but it is invasive, expensive and uncomfortable
      for the patient. Recently, we demonstrated a novel approach for the detection of
      primary bladder cancer based on microsatellite analysis of urine DNA. To
      determine the feasibility of this technique for following-up patients with TCC,
      we tested serial urine samples from 21 patients who had been treated for bladder
      cancer with 20 polymorphic microsatellite markers in a blinded fashion. We
      detected recurrent lesions in 10 out of 11 patients and correctly predicted the
      existence of a neoplastic cell population in the urine of two patients, 4 and 6
      months before cystoscopic evidence of the tumor. The assay was negative in 10 of
      10 patients who had no evident cancer. Microsatellite analysis of urine sediment
      represents a novel and potentially powerful clinical tool for the detection of
      recurrent bladder cancer.

PMID- 9176488
TI  - Flt3 ligand induces tumor regression and antitumor immune responses in vivo.
AB  - Daily treatment of mice with recombinant human Flt3 ligand (huFlt3L) results in a
      dramatic numerical increase in the number of dendritic cells (DCs) in vivo. Since
      DCs are pivotal in the induction of immune responses, we tested whether Flt3L
      treatment of mice challenged with a syngeneic methylcholanthrene (MCA)-induced
      fibrosarcoma would augment the generation of effective antitumor immune responses
      in vivo. Flt3L treatment not only induced complete tumor regression in a
      significant proportion of mice, but also decreased tumor growth rate in the
      remaining mice. A preliminary characterization of the cellular mechanisms
      involved suggests that Flt3L may be important in the treatment of cancer in situ
      through the generation of specific antitumor immune responses.

PMID- 9176489
TI  - Restoration of the growth suppression function of mutant p53 by a synthetic
      peptide derived from the p53 C-terminal domain.
AB  - We demonstrate here that synthetic 22-mer peptide 46, corresponding to the
      carboxy-terminal amino acid residues 361-382 of p53, can activate specific DNA
      binding of wild-type p53 in vitro and can restore the transcriptional
      transactivating function of at least some mutant p53 proteins in living cells.
      Introduction of peptide 46 in Saos-2 cells carrying a Tet-regulatable His-273
      mutant p53 construct caused growth inhibition and apoptosis in the presence of
      mutant p53 but not in its absence, confirming that the effect of the peptide is
      mediated by reactivation of mutant p53. Moreover, peptide 46 caused apoptosis in
      mutant as well as wild-type p53-carrying human tumor cell lines of different
      origin, whereas p53 null tumor cells were not affected. These findings raise
      possibilities for developing drugs that restore the tumor suppressor function of
      mutant p53 proteins, thus selectively eliminating tumor cells.

PMID- 9176491
TI  - Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and
      megacolon.
AB  - The isolated homeobox gene Enx (Hox11L1) is expressed in enteric neurons
      innervating distal ileum, and proximal and distal colon. Enx-deficient mice
      develop megacolon with massive distension of the proximal colon. The number of
      myenteric ganglia, total neurons per ganglion, and NADPH diaphorase presumptive
      inhibitory neurons per ganglion are increased in the proximal and distal colon,
      but decreased in the distal ileum of all Enx-/- mice. Enx-/- mice provide a model
      for human neuronal intestinal dysplasia (NID), in which myenteric neuronal
      hyperplasia and megacolon are seen. These results suggest that Enx is required
      for the proper positional specification and differentiative cell fate of enteric
      neurons.

PMID- 9176490
TI  - ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and
      antitumoral efficacy that can be augmented by standard chemotherapeutic agents.
AB  - The 55-kilodalton (kDa) protein from the E1B-region of adenovirus binds to and
      inactivates the p53 gene, which is mutated in half of human cancers. We have
      previously shown that the replication and cytopathogenicity of an E1B, 55-kDa
      gene-attenuated adenovirus, ONYX-015, is blocked by functional p53 in RKO and
      U20S carcinoma lines. We now report that normal human cells were highly resistant
      to ONYX-015-mediated, replication-dependent cytolysis. In contrast, a wide range
      of human tumor cells, including numerous carcinoma lines with either mutant or
      normal p53 gene sequences (exons 5-9), were efficiently destroyed. Antitumoral
      efficacy was documented following intratumoral or intravenous administration of
      ONYX-015 to nude mouse-human tumor xenografts; efficacy with ONYX-015 plus
      chemotherapy (cisplatin, 5-fluorouracil) was significantly greater than with
      either agent alone.

PMID- 9176492
TI  - Long-term protection of chimpanzees against high-dose HIV-1 challenge induced by
      immunization.
AB  - A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1MN
      gp160 recombinants followed by boosting with HIV-1SF2 gp120 was evaluated in
      chimpanzees. Long-lasting protection, requiring only three immunizations, was
      achieved against a low-dose challenge with the SF2 strain of HIV-1 and a
      subsequent high-dose SF2 challenge administered 1 year later without an
      intervening boost. Notably, neutralizing antibody responses against both clinical
      and laboratory isolates developed in three chimpanzees and persisted until the
      time of high-dose challenge. The possibility that cytotoxic T-lymphocytes
      contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies
      is suggested. Our results validate the live vector priming/subunit booster
      approach and should stimulate interest in assessing this combination vaccine
      approach in humans.

PMID- 9176493
TI  - Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection:
      inhibition of mRNA expression.
AB  - Interleukin-16 (IL-16) is secreted by activated CD8+ T lymphocytes and acts on
      CD4+ T lymphocytes, monocytes and eosinophils. Recently, the C-terminal 130-amino
      acid portion of IL-16 was shown to suppress HIV-1 replication in vitro. To
      explore the potential of human IL-16 for gene therapy, this portion was
      transfected into HIV-1-susceptible CD4+ jurkat cells by means of a mammalian
      expression vector. The stable transfectants synthesized and secreted IL-16
      protein. The expression of IL-16 did not alter growth rate and CD4 expression;
      however, HIV replication was inhibited by as much as 99%. Furthermore, during the
      initial phase of the infection, equal amounts of HIV-1 proviral DNA were found in
      cells transfected with IL-16 and with vector alone. In contrast, the 2-kilobase
      HIV-1 transcripts were markedly reduced and the 4-kb and 9-kb transcripts were
      undetectable in the cells transfected with IL-16. These findings indicate that IL
      16-mediated inhibition of HIV-1 is not at the level of viral entry or reverse
      transcription, but at messenger RNA expression.

PMID- 9176494
TI  - Prophylaxis against HIV-1 infection in chimpanzees by nevirapine, a nonnucleoside
      inhibitor of reverse transcriptase.
AB  - Chimpanzees were challenged with HIV-1IIIB while receiving a short regimen of
      nevirapine (Viramune), a nonnucleoside inhibitor of HIV-1 reverse transcriptase.
      The untreated, control chimpanzee developed an infection characterized by
      seroconversion, viremia in peripheral blood mononuclear cells (PBMCs), and plasma
      positive for viral RNA. In contrast, the three nevirapine-treated chimpanzees
      remained negative for all viral markers with the exception of nested polymerase
      chain reaction (PCR) analysis of PBMCs for viral DNA. Although PBMCs from the
      three nevirapine-treated chimpanzees tested intermittently positive for viral
      DNA, this PCR signal disappeared and remained negative for the final five months
      of the study. These data indicate that orally administered nevirapine provided
      protection from HIV-1 infection in the chimpanzee model.

PMID- 9176495
TI  - Globus pallidus stimulation activates the cortical motor system during
      alleviation of parkinsonian symptoms.
AB  - Studies of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      parkinsonism in monkeys suggest that excessive inhibitory outflow from the
      internal segment of the globus pallidus (GPi) suppresses the motor thalamus,
      which reduces activation of the cerebral cortex motor system, resulting in the
      slowness and poverty of movement of Parkinson's disease (PD). This hypothesis is
      supported by reports of high rates of spontaneous neuronal discharges and
      hypermetabolism in GPi (ref. 4-7) and impaired activation of the supplementary
      motor area (SMA) and dorsolateral prefrontal regions in PD patients. Furthermore,
      lesion or chronic high-frequency electrical (likely inactivating) stimulation of
      GPi (ref. 10-14) is associated with marked improvements in akinesia and rigidity,
      and the impaired activation of SMA is reversed when the akinesia is treated with
      dopamine agonists. To test whether improvement in motor function with pallidal
      surgery can be attributed to increased activity in premotor cortical regions, we
      assessed the changes in regional cerebral blood flow (rCBF) and parkinsonian
      symptoms during disruption of GPi activity with high-frequency stimulation
      delivered through implanted brain electrodes. Positron emission tomography (PET)
      revealed an increase in rCBF in ipsilateral premotor cortical areas during GPi
      stimulation, which improved rigidity and bradykinesia. These results suggest that
      disrupting the excessive inhibitory output of the basal ganglia reverses
      parkinsonism, via a thalamic relay, by activation of brain areas involved in the
      initiation of movement.

PMID- 9176496
TI  - Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats.
AB  - Pulmonary emphysema is a common disease in which destruction of the lung's gas
      exchange structures (alveoli) leads to inadequate oxygenation, disability and
      frequently death; lung transplantation provides its only remediation. Because
      treatment of normal rats with all-trans-retinoic acid increases the number of
      alveoli, we tested whether a similar effect would occur in rats with emphysema.
      Elastase was instilled into rat lungs, producing changes characteristic of human
      and experimental emphysema: increased lung volume reflecting a loss of lung
      elastic recoil, larger but fewer alveoli and diminished volume-corrected alveolar
      surface area due to destruction of alveolar walls. Treatment with all-trans
      retinoic acid reversed these changes providing nonsurgical remediation of
      emphysema and suggesting the possibility of a similar effect in humans.

PMID- 9176497
TI  - Monocyte deactivation in septic patients: restoration by IFN-gamma treatment.
AB  - Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha
      (TNF-alpha) or interleukin-1 (IL-1), decreases mortality in several animal models
      of sepsis. However, recent clinical trials did not show an unequivocal
      improvement in survival. In contrast to animals, which succumb to shock during
      the first 72 hours, we found that many patients die much later with signs of
      opportunistic infections accompanied by downregulation of their monocytic HLA-DR
      expression and reduced ability to produce lipopolysaccharide (LPS)-induced TNF
      alpha in vitro. This phenomenon of monocyte deactivation in septic patients with
      fatal outcome shows similarities to experimental monocytic refractoriness induced
      by LPS desensitization or by pretreatment with its endogenous mediators IL-10 and
      transforming growth factor-beta (TGF-beta). In order to strengthen their
      antimicrobial defense, here we tested whether interferon-gamma (IFN-gamma) can
      improve monocytic functions in these patients and in experimental monocytic
      deactivation. The considerably lowered in vitro levels of LPS-induced TNF-alpha
      in these situations were significantly enhanced by IFN-gamma, but did not reach
      the extremely high levels of IFN-gamma primed naive cells from healthy donors.
      Moreover, IFN-gamma applied to septic patients with low monocytic HLA-DR
      expression restored the deficient HLA-DR expression and in vitro LPS-induced TNF
      alpha secretion. Recovery of monocyte function resulted in clearance of sepsis in
      eight of nine patients. These data suggest that IFN-gamma treatment in carefully
      selected septic patients is a novel therapeutic strategy worth pursuing.

PMID- 9176498
TI  - Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate
      established tumors.
AB  - The 4-1BB glycoprotein is a member of the tumor necrosis factor receptor
      superfamily and binds to a high-affinity ligand (4-1BBL) expressed on several
      antigen-presenting cells such as macrophages and activated B cells. Expression of
      4-1BB is restricted to primed CD4+ and CD8+ T cells, and 4-1BB signaling either
      by binding to 4-1BBL or by antibody ligation delivers a dual mitogenic signal for
      T-cell activation and growth. These observations suggest an important role for 4
      1BB in the amplification of T cell-mediated immune responses. We now show that
      administration of anti-4-1BB monoclonal antibodies can eradicate established
      large tumors in mice, including the poorly immunogenic Ag104A sarcoma and the
      highly tumorigenic P815 masto cytoma. The immune response induced by anti-4- 1BB
      monoclonal antibodies is mediated by both CD8+ and CD4+ T cells and is
      accompanied by a marked augmentation of tumor-selective cytolytic T-cell
      activity. Our data suggest that a similar approach may be efficacious for
      immunotherapy of human cancer.

PMID- 9176500
TI  - Selectively infective phage (SIP) technology: a novel method for in vivo
      selection of interacting protein-ligand pairs.

PMID- 9176499
TI  - Novel retinoid-related molecules as apoptosis inducers and effective inhibitors
      of human lung cancer cells in vivo.
AB  - Lung cancer causes more than 140,000 deaths annually in the United States alone,
      and the prognosis for non-small cell lung cancer (NSCLC) is particularly poor.
      Therapies using small molecules that preferentially kill lung tumor cells by
      inducing cellular suicide (apoptosis) would therefore be highly desirable.
      Retinoids have shown promise as cancer preventive and cancer therapeutic agents.
      Retinoid signals are mediated by two classes of nuclear receptors: the retinoic
      acid receptors (RAR alpha, beta, and gamma) and the retinoid X receptors (RXR
      alpha, beta and gamma). These receptors usually bind as heterodimers to specific
      DNA sequences and/or interact with other transcriptional regulators, such as AP-1
      (ref. 10) to regulate gene transcription. Synthetic retinoids can be made that
      activate only specific portions of the complex retinoid response network and
      activate selective biological programs. To identify retinoids with novel
      biological activities, we used a high-throughput "biological activity
      fingerprint" screen on a large library of retinoids and retinoid-related
      molecules (RRMs). We identified new structures that are highly effective against
      lung cancer cells in vitro, inducing apoptosis. We show here for one of these
      compounds that it is very effective against a human NSCLC in vivo in an animal
      model. These new molecules show a distinct pattern of receptor signaling.

PMID- 9176503
TI  - The marital relationship and health in women with chronic fatigue and immune
      dysfunction syndrome: views of wives and husbands.
AB  - The purpose of this study was to describe the association between the marital
      relationship and the health of the wife with chronic fatigue and immune
      dysfunction syndrome (CFIDS). The convenience sample of 131 wives with CFIDS and
      their spouses reported their marital relationships similarly, but the wives
      reported higher CFIDS symptom scores. Marital adjustment scores, wives' conflict
      scores, and husbands' self-empathy scores were associated with wives' CFIDS
      symptom scores. Hierarchical multiple regression models showed wives with higher
      education, lengthier marriages, dyads with higher marital adjustment, and wives
      with less conflict and less support were predictive of lower problematic CFIDS
      symptoms.

PMID- 9176501
TI  - Improving dressing behavior in cognitively impaired nursing home residents.
AB  - This study tested the extent to which a behavioral intervention, Strategies to
      Promote Independence in Dressing (SPID), improved dressing independence among 90
      cognitively impaired nursing home residents (average score on Mini Mental Status
      Exam = 7.35 +/- .69). The effect of SPID on caregiving efficiency, the time
      required for nursing assistants to use the strategies, was also examined. The
      results showed improved independence (decrease in assistance) from 6.08 +/- .12
      at baseline to 4.93 +/- .19 following 6 intervention weeks. This significant
      improvement in dressing independence occurred without a clinically relevant
      increase in caregiver time (less than 1 min). Seventy-five percent of the
      subjects improved one or more levels of dressing independence, and more than 20%
      achieved their maximum intervention effect during the first week of treatment.

PMID- 9176502
TI  - HIV-risk behaviors and mental health characteristics among homeless or drug
      recovering women and their closest sources of social support.
AB  - This article describes risky drug and sexual behavior and mental health
      characteristics in a sample of 240 homeless or drug-recovering women and their
      most immediate sources of social support. Women and their closest support sources
      both reported a great deal of recent noninjection drug use (56% and 52%,
      respectively) and lesser, though similar amounts of recent injection drug use
      (12% and 14%, respectively). More than one third of both groups reported a
      history of sexually transmitted disease and sexual activity with multiple
      partners. Fifty-one percent of the women and 31% of their support sources had
      Center for Epidemiological Studies Depression Scale (CES-D) scores of 27 or
      greater, suggesting a high level of depressive disorders in both samples.
      Similarly, 76% of the women and 59% of their support sources had psychological
      well-being scores below a standard clinical cutoff point. These data suggest that
      homeless and impoverished women turn to individuals who are themselves at high
      risk for emotional distress and risky behaviors as their main sources of support.

PMID- 9176504
TI  - Correlates of pain-related responses to venipunctures in school-age children.
AB  - Guided by the Roy Adaptation Model of Nursing, the relationship of children's
      age, gender, exposure to past painful experiences, temperament, fears, and child
      rearing practices to their pain responses to a venipuncture was examined. A
      sample of 94 children aged 8 to 12 years and their female caregivers were
      recruited from three outpatient clinics. During the venipuncture, children's
      behavioral and heart rate responses were monitored; immediately after, their
      subjective responses were recorded. Canonical correlation revealed two variates.
      In the first, age and threshold (temperamental dimension) correlated with pain
      quality, behavioral responses, and heart rate responses, explaining 12% of the
      variance. In the second, age, the temperamental dimensions of distractibility and
      threshold, and medical fears explained only 5.7% of the variance in pain quality
      and heart rate magnitude. Significant correlations between pain intensity,
      quality, behavioral responses, and heart rate responses support the
      multidimensionality of pain.

PMID- 9176505
TI  - The theory of planned behavior applied to cigarette smoking in African-American,
      Puerto Rican, and non-Hispanic white teenage females.
AB  - The purpose of the study was to evaluate the adequacy of Ajzen's Theory of
      Planned Behavior to predict cigarette-smoking intention in three groups of
      teenage females. Participants were 141 African-Americans, 146 Puerto Ricans, and
      143 non-Hispanic whites, 13 to 19 years of age. Consistent with the Theory of
      Planned Behavior, path analysis revealed direct relationships among attitude,
      subjective norm, perceived behavioral control, and smoking intention for African
      Americans. For Puerto Ricans and non-Hispanic whites, only the relationships
      among attitude, perceived behavioral control, and smoking intention were
      supported. Subjective norm was not found to be a significant predictor of smoking
      intention for these two groups. The results suggest that the Theory of Planned
      Behavior provides an empirically adequate explanation of cigarette smoking among
      female African-American teenage women.

PMID- 9176506
TI  - Job satisfaction and organizational attachment of nurses holding doctoral
      degrees.
AB  - A model explaining job satisfaction and organizational attachment (commitment and
      intent to leave) was estimated for a national sample of nurses holding doctoral
      degrees and employed in academic and nonacademic setting. The purpose of the
      study was (a) to test a model from Price-Mueller that has been used primarily for
      nurses who do not have their doctorates and (b) to determine if the results of
      the test were consistent with expectations from the professions literature The
      results showed that although nursing is categorized as a semiprofession in the
      professions literature, the satisfaction and attachment of nurses holding
      doctorate degrees was explained by variables from arguments about numbers of the
      well-established professions, known as "true" professions.

PMID- 9176507
TI  - Estimates of stability of daily wandering behavior among cognitively impaired
      long-term care residents.
AB  - Direct observation and time-study techniques were used with a sample of 25
      ambulatory, cognitively impaired subjects drawn from two long-term care settings
      to evaluate wandering behavior. The purposes of this study were (a) to describe
      the 24-hour distribution of wandering and direct ambulating cycles, (b) to
      examine the stability of wandering behavior over a 3-day interval, (c) to
      evaluate whether wandering during a 2-hour epoch is representative of that of a
      24-hour day, and (d) to evaluate whether large-scale integrated (LSI) activity
      meters can substitute as an index or proxy for direct observation in the study of
      wandering behavior. Subjects displayed a daily average of 20.1 cycles
      encompassing 43.9 minutes of wandering ambulation and 28.8 cycles encompassing
      40.4 minutes of direct ambulation. Wandering behavior was present in all
      subjects. However, wandering was highly variable from subject to subject. For a
      given subject, wandering was only moderately stable over a 3-day interval, but
      more so than direct ambulation. Similarly, a standard 2-hour epoch was moderately
      representative of daily wandering ambulation, but more so than for direct
      ambulation. Finally, LSI meters, when applied at the ankle and worn over longer
      (24-hr) rather than shorter (2-hr) intervals, are a promising means to index
      wandering behavior.

PMID- 9176508
TI  - The challenge of using Likert-type scales with low-literate ethnic populations.

PMID- 9176509
TI  - Incorporating auxiliary variables into probability sampling designs.

PMID- 9176510
TI  - Suicide genes and bystander killing: local and distant effects.

PMID- 9176511
TI  - Neurotoxicity of intracerebral injection of a replication-defective adenoviral
      vector in a semipermissive species (cotton rat).
AB  - The neurotoxicity of an adenoviral vector (Adv.RSVtk) carrying the gene for
      herpes simplex virus thymidine kinase (HSVtk) was tested in the cotton rat, a
      semipermissive host. Adv.RSVtk was injected intracerebrally in cotton rats at a
      dose of 5.0 x 10(6) or 7.5 x 10(7) p.f.u. No signs of illness were observed.
      Histological inspection at 12 and 28 days after injection showed inflammation of
      the ependyma and choroid plexus and at the injection site. No demyelination,
      viral inclusions, cerebral edema, necrosis, cavities or vascular necrosis were
      seen in the brains. There was no significant difference between animals injected
      with 5.0 x 10(6) or 7.5 x 10(7) p.f.u., nor was there a difference between
      animals analyzed at 12 or 28 days after vector injection. This inflammation was
      similar in animals that had been preimmunized with wild-type virus and in animals
      that had been treated with ganciclovir. No histopathology, was observed in the
      lungs of the animals and no replication-competent virus was detected. These
      experiments indicate that Adv.RSVtk has limited neurotoxicity which would not
      prohibit its use in a limited phase I clinical trial in humans that have
      malignant tumors of the central nervous system.

PMID- 9176512
TI  - Gene therapy of experimental malignant mesothelioma using adenovirus vectors
      encoding the HSVtk gene.
AB  - Replication-defective adenovirus vectors were generated in which the gene of
      interest (lacZ, luciferase or HSV-tk) is driven by the adenovirus major late
      promoter (MLP) or the human cytomegalovirus immediate-early gene
      promoter/enhancer (CMV). In vitro experiments with rat (II-45) and human (MERO
      25) mesothelioma cell lines revealed that the CMV promoter was stronger than the
      MLP promoter regarding levels of expression of the luciferase reporter gene and
      ganciclovir (GCV) killing efficiency after tk gene transfer. Following
      administration of IG.Ad.CMV.lacZ recombinant adenovirus (Introgene, IG) into the
      pleural cavity of Fischer rats with established mesothelioma, a widespread
      distribution of infectious virus particles through the thorax contents was
      demonstrated. However, a relatively small proportion of tumor cells were
      transduced. Nevertheless, a strong tumor growth inhibition was observed following
      treatment with IG.Ad.CMV.TK recombinant adenovirus and GCV. Separate groups of
      rats inoculated on day 0 with 10(5) II-45 cells in the pleural cavity, received 7
      x 10(9) infectious particles of IG.Ad. CMV.TK on day 1, day 2, day 4 or day 8.
      One day after virus administration, 25 mg/kg GCV or PBS (controls) was injected
      i.p. (intraperitoneally) twice daily. On day 15, all animals were killed.
      Significant tumor regression, equivalent to 5 log cell kill, occurred in the
      treated rats suggesting an impressive bystander effect. In a survival study,
      animals were treated 9 days after inoculation of 10(5) tumor cells with
      IG.Ad.CMV.TK and a 14 days course of GCV. This treatment prolonged symptom-free
      survival time from 19 days in the controls to 33 days in the treated group. These
      responses can be best explained by assuming continued tk expression in or around
      the tumor tissue during GCV treatment. Our results confirm and extend earlier
      findings with the same model and demonstrate the potential of the herpes simplex
      virus thymidine kinase suicide gene therapy as a local treatment for malignant
      mesothelioma.

PMID- 9176513
TI  - Studies on the effect of the combined expression of anti-tat and anti-rev genes
      on HIV-1 replication.
AB  - A series of retroviral vectors with potential anti-tat and antirev activity was
      developed. Vectors containing a tat transdominant negative mutant (tat22/37) and
      an RRE decoy in different positions, directed by the same promoter or by
      different promoters, were generated. Retroviral vectors containing tat22/37 and
      the RevM10 transdominant negative mutant were also constructed. Jurkat cells were
      transduced with the recombinant retroviruses to produce monoclonal and polyclonal
      cultures. In these cell lines the recombinant proviruses were correctly
      integrated and expression of the inserted genes was detected by Northern blot or
      RT-PCR analysis. However, infection of these cell lines with HIV-1 showed that
      none of these recombinant constructs inhibited virus replication at a high
      multiplicity of infection (MOI). At a low MOI, two cell clones containing
      tat22/37 and the RRE decoy in 3' position showed a long lasting protection
      against virus replication, in comparison to control cultures expressing tat22/37
      or RRE alone. Combination of tat and rev mutants was ineffective in inhibiting
      HIV-1 replication at both low and high MOIs. At a low MOI, HIV-1 replication was
      efficiently blocked in two cell clones expressing the RevM10 mutant alone. These
      results show a synergic effect of anti-tat and anti-rev molecules when the RRE
      sequence is cloned 3' to tat22/37, suggesting the possibility of using this
      vector design to control HIV-1 replication.

PMID- 9176514
TI  - Lymphocyte apoptosis: induction by gene transfer techniques.
AB  - Efficient gene transfer of lymphocytes has been shown to be extremely difficult.
      The molecular background for this gene transfer resistance is not completely
      understood. We reasoned that apoptosis may play a role in this gene transfer
      resistance of lymphocytes. We show that transfection of lymphocytes via nonviral
      vectors leads to induction of apoptosis in a significant proportion of cells.
      Since apoptosis may be mediated via the TNF alpha and TNF alpha receptor pathway,
      we studied the amount of TNF secreted by transfected lymphocytes. The percentage
      of apoptotic lymphocytes correlated well with TNF alpha secretion. TNF secretion
      was dependent on the gene transfection method used. High amounts of TNF secretion
      were detected using receptor-mediated gene transfer and lipofection. In contrast,
      only low amounts of TNF were detected after electroporation and retroviral gene
      transfer. In receptor-mediated gene transfer, TNF secretion was due to the use of
      anti-CD3 antibody. Induction of apoptosis and increase in necrosis was blocked
      using an anti-TNF antibody. This blockage led to a significant increase in the
      proliferation rate of lymphocytes transfected with the interleukin-2 or
      interleukin-7 gene. In conclusion, gene transfer techniques led to TNF secretion,
      apoptosis and necrosis of lymphocytes. This could be blocked using an anti-TNF
      antibody. Blockage of apoptosis after gene transfer should have an impact on the
      use of lymphocytes transfected with cytokine genes as immunologic effector cells
      in cancer gene therapy protocols.

PMID- 9176515
TI  - Loss of retroviral gene expression in bone marrow reconstituted mice correlates
      with down-regulation of gene expression in long-term culture initiating cells.
AB  - The question of whether a retroviral vector is expressed in vivo after infection
      of hematopoietic stem cells remains unpredictable. In this study, we show that a
      switch off of retroviral sequences can be tested in vitro using the long-term
      bone marrow culture system. The time kinetics of the down-regulation of
      retroviral expression in vitro and in vivo have been demonstrated to be similar.
      The correlation of switch off events in both systems allows for evaluation of
      retroviral expression in vitro provided the silencing is caused by viral
      sequences. This approach could be useful for testing vectors for gene
      therapeutical applications of the hematopoietic system.

PMID- 9176516
TI  - Macrophage depletion increases the safety, efficacy and persistence of adenovirus
      mediated gene transfer in vivo.
AB  - The consequences of macrophage depletion achieved by intravenous infusion of
      liposome-encapsulated clodronate (dichlormethylene diphosphonate (Cl2MDP)) on
      adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin (hAAT)
      gene were examined in 12-14-week-old male Balb/c mice. The levels of hAAT
      expression following tail vein infusions of 10(9) p.f.u. of Ad.RSV-hAAT were
      approximately four-fold higher in macrophage-depleted animals than in control
      animals pretreated with liposome-encapsulated phosphate-buffered saline (PBS).
      Clodronate pretreatment also significantly increased the survival of animals
      injected with high doses of viral vector. Long-term studies performed in animals
      receiving tail vein infusions of the adenoviral vector also indicated that
      clodronate pretreatment significantly attenuated the rapid loss of transgene
      expression usually observed in immunocompetent animals. These findings indicate
      that the depletion of macrophages before adenovirus-mediated gene transfer may
      increase the transduction efficiency and reduce the rate of immunologic
      elimination of the adenovirally transduced cells, thereby increasing the
      persistence of transgene expression in immunocompetent animals.

PMID- 9176517
TI  - An intracellular anti-erbB-2 single-chain antibody is specifically cytotoxic to
      human breast carcinoma cells overexpressing erbB-2.
AB  - We previously demonstrated that delivery of a gene encoding an anti-erbB-2
      intracellular single-chain antibody (sFv) resulted in down-regulation of cell
      surface erbB-2 levels and induction of apoptosis in erbB-2 overexpressing ovarian
      cancer cells. Based upon these findings, we hypothesized that human breast
      carcinomas overexpressing erbB-2 would be similarly affected by this genetic
      intervention. We evaluated the phenotypic effects resulting from intracellular
      expression of the anti-erbB-2 sFv on the human breast cancer cell lines MDA-MB
      361, SK-BR-3, BT-474, MCF-7 and MDA-MB-231. Recombinant adenoviruses encoding
      either a reporter gene (AdCMVLacZ) or the endoplasmic reticulum (ER) directed
      anti-erbB-2 sFv (Ad21) were delivered to various breast cancer cell lines. Cell
      viability was determined by a proliferation assay and fluorescent microscopy
      allowed visualization of apoptotic cells. An erbB-2 ELISA quantified the
      endogenous erbB-2 levels of each cell line. The anti-erbB-2 sFv-encoding
      adenovirus, Ad21, but not the beta-galactosidase encoding adenovirus, AdCMVLacZ,
      was cytotoxic to > 95% of the tumor cells in the MDA-MB-361 and SK-BR-3 lines,
      and > 60% of the tumor cells in the BT-474 line. In marked contrast, the MCF-7
      and MDA-MB-231 cell lines showed no change in the rate of cell proliferation
      following this treatment. The cytotoxic effects generated in the first three
      lines were a consequence of the induction of apoptosis by the anti-erbB-2 sFv. An
      ELISA specific for erbB-2 showed that the breast cancer cell lines most
      susceptible to the anti-erbB-2 sFv, MDA-MB-361, SK-BR-3 and BT-474, overexpressed
      the erbB-2 protein while the cell lines demonstrating no response to the anti
      erbB-2 sFv, MCF-7 and MDA-MB-231, expressed the lowest levels of erbB-2. These
      results demonstrate that targeted killing of erbB-2 overexpressing cells via
      intracellular knockout can be accomplished in the context of breast carcinoma.
      Furthermore, erbB-2 levels in breast tumor cells may be predictive of their
      sensitivity to sFv-mediated killing. The ability to accomplish selective
      cytotoxicity of breast cancer cell lines overexpressing the erbB-2 tumor marker
      should allow for derivation of clinical gene therapy strategies for breast cancer
      utilizing this approach.

PMID- 9176518
TI  - Efficient purification of plasmid DNA for gene transfer using triple-helix
      affinity chromatography.
AB  - Plasmid DNA used for nonviral therapeutic gene transfer or nucleic acid
      vaccination has to be highly purified devoid of contaminating components such as
      bacterial proteins, endotoxins, or bacterial chromosomal DNA. We have developed a
      new affinity chromatography technique for plasmid DNA purification: triple-helix
      affinity chromatography (THAC). This technique is based on the sequence-specific
      interaction of an oligonucleotide forming a triple-helix with plasmid DNA. The
      oligonucleotide was covalently linked to a chromatographic matrix, thus providing
      a reusable affinity support. By inserting a suitable homopurine sequence in the
      plasmid DNA, it is possible to obtain a triple-helix interaction that will only
      be stable at mild acidic pH and that will dissociate in alkaline conditions. A
      crude lysate from a recombinant E. coli, or a pre-purified plasmid DNA, is thus
      applied at acidic pH on to a THAC column. After extensive washing of the column,
      purified plasmid DNA is eluted using an alkaline buffer. The binding conditions
      of the plasmid DNA on to the column have been optimized, as well as the
      hybridization sequence and the linker group between the matrix and the third
      strand oligonucleotide. The THAC technique makes it possible to purify in one
      step supercoiled plasmid DNA, and to significantly reduce the level of
      contaminating RNA, endotoxins and chromosomal DNA. In particular, a 100-fold
      reduction of chromosomal DNA contamination over that obtained with conventional
      techniques can be achieved through a single additional THAC step. Further
      improvements of THAC technology are possible, and we anticipate that this
      technique can be scaled up for integration into a full commercial-scale DNA
      production process.

PMID- 9176520
TI  - A novel, membrane receptor-based retroviral vector for Fanconi anemia group C
      gene therapy.
AB  - Retroviral vectors are effective shuttle systems by introducing therapeutically
      relevant genes stably into the genome of proliferating cells. The majority of
      vectors applied for research or clinical applications use neomycin for cell
      selection and identification. To circumvent the time consuming and potentially
      toxic G418 selection process in transduction studies we constructed a novel
      marker vector using I-NGFR as a cell surface marker to identify DNA repair
      defective Fanconi anemia cells complemented with the FAC gene. The new vector
      constructed is based on a MoMLV backbone, a signal peptide-deleted I-NGFR
      receptor gene under control of a LTR promoter and the therapeutically relevant
      FAC gene placed downstream of a SV40 promoter. Supernatants containing high
      titers of amphotropic viruses from FACS cloned cell cultures were obtained and
      tested for primary transduction rates, rapid detection of transduced cells within
      48 h and correction of mitomycin C-induced cell cycle G2 phase accumulation in a
      single assay using multiparameter, dual laser flow cytometry. Primary
      transduction efficiency detected via (I-NGFR) antibody was between 5% and 30%
      with Fanconi cell lines, 5% with CD34+ cells and 15% with PBLs. MMC-induced G2
      phase cell cycle disturbances were fully complemented in Fanconi anemia B cell
      lines of complementation group C but not in B cell lines of another FA
      complementation group (D). In addition to the normalization of the G2 phase
      arrest, induction of cell death in the FAC cell line was also decreased three to
      10-fold at different MMC concentrations.

PMID- 9176519
TI  - Gene transfer into enteric neurons of the rat small intestine in organ culture
      using a replication defective recombinant herpes simplex virus type 1 (HSV1)
      vector, but not recombinant adenovirus vectors.
AB  - We have designed a system in which to test gene transfer into gut neurons
      consisting of an organ culture of neonatal rat small intestine. The tissue was
      exposed to herpes simplex- and adenovirus-derived vectors: (1) a temperature
      sensitive herpes simplex virus-1 (HSV1) vector (tsK-beta gal) containing the lacZ
      gene encoding beta-galactosidase (beta-gal), under the transcriptional control of
      the HSV1 immediate-early 3 (IE3) promoter; (2) RAd35, an E1-/E3- replication
      deficient adenovirus expressing lacZ under the control of a truncated HCMV major
      IE promoter; and (3) RAd122, an E1-/E3- replication-deficient adenovirus
      expressing the lacZ under the control of the RSV LTR. Forty-eight hours after the
      vector was added to the organ culture, we detected beta-gal using
      immunohistochemistry or X-gal histochemistry in tissue sections examined by light
      microscopy. We encountered a distinctive staining of cells arranged in two
      concentric circles corresponding in location to the myenteric and submucosal
      plexuses. Cells in these areas were of similar size and morphology to neonatal
      enteric neurons, as visualized by NADPH-diaphorase histochemistry and
      immunocytochemical staining with antibodies to the neuronally expressed proteins
      PGP 9.5, or neurofilaments. Double labelling with antibodies recognizing
      neurofilaments and beta-galactosidase revealed that most cells infected by tsK
      were neurons, while the RAd35 and 122 vectors only infected non-neuronal cells.
      We thus demonstrate that both HSV1- and adenovirus-derived vectors can be used to
      transfer genes to the gut in vitro, but they transduce different populations of
      target cells.

PMID- 9176521
TI  - In vivo gene therapy of malignant tumours with heat shock protein-65 gene.
AB  - We have previously shown that ex vivo insertion of a gene encoding the
      mycobacterial heat shock protein-65 into tumour cells results in their inability
      to form tumours in mice. We report regression of highly malignant reticulum cell
      sarcomas (J774) after liposome-mediated gene transfer in vivo. Heat shock gene
      transfer resulted in tumour regression both in immunocompetent and
      immunodeficient SCID mice. Complete tumour eradication, however, was detected
      only in immunocompetent animals, confirming the role of T cells in tumour
      rejection. Treatment of tumour bearing mice with the heat shock gene-liposome
      complex resulted in the production of antibodies against the tumour cells,
      indicating an increase in the antigenicity of the tumour after gene transfer.
      These results suggest that the heat shock protein-65 gene could provide a novel
      approach for the treatment of established tumours.

PMID- 9176523
TI  - Combination gene transfer to potentiate tumor regression.
AB  - Recent efforts to treat malignancy using gene transfer have met with varying
      degrees of success. In this paper, we report the results of studies using two
      recombinant adenoviral vectors to examine the efficacy of combination gene
      transfer to cause tumor regression in vivo. One of these vectors encodes the
      murine MHC class I gene, H-2Kb (ADV-Kb), which induces an immune response that
      stimulates tumor regression. The second vector encodes the human p21 cyclin
      dependent kinase inhibitor (ADV-p21). This gene product arrests cell cycle
      progression and prevents proliferation of tumor cells. Both vectors were tested
      in a murine model in vivo for antitumor effect. As previously shown, a
      significant reduction of tumor size was observed with each vector. Combination
      treatment, in which both vectors were administered, resulted in a trend toward a
      reduced tumor growth greater than with either vector alone. In order to
      characterize the mechanism of tumor regression, cytolytic T lymphocyte (CTL)
      assays against the allogeneic molecule, H-2Kb, were performed. Mice treated with
      ADV-Kb showed specific CTL activity against the H-2Kb molecule, demonstrating
      that the immune response against the H-2Kb gene product involved in tumor
      regression was potentiated by expression of the p21 gene which affects cell cycle
      progression.

PMID- 9176522
TI  - Heterologous expression of adenovirus E3-gp19K in an E1a-deleted adenovirus
      vector inhibits MHC I expression in vitro, but does not prolong transgene
      expression in vivo.
AB  - An E1a-deleted adenovirus vector constitutively expressing native adenovirus E3
      gp19K (Ad.RSV-gp19K) was constructed in order to determine whether or not E3
      gp19K mediated interference with antigen presentation would result in prolonged
      transgene expression in vivo. Cultured fibroblasts infected with Ad.RSV-gp19K
      produced a native size gp19K protein and had decreased cell surface levels of MHC
      I as shown by immunoprecipitation and flow cytometry. The congenic mouse strains
      Balb/b (H-2b MHC I with high gp19K affinity), Balb/k (H-2k MHC I with no gp19K
      affinity), and Balb/c (H-2d MHC I with moderate gp19K affinity) were chosen for
      in vivo experiments because of their range of gp19K affinities. Following
      transduction of mice form each strain with Ad.RSV-gp19K and AD/RSV-hAAT (a
      reporter adenovirus), or Ad/RSV-cFIX (control adenovirus) and Ad/RSV-hAAT, the
      level and duration of serum hAAT protein were unrelated to gp19K protein
      expression. Evaluation of MHC I abundance on hepatocytes following in vivo
      transduction demonstrated that recombinant adenovirus rapidly increased the
      abundance of surface MHC I molecules on hepatocytes, and surface MHC I molecules
      were reduced earlier and to a greater extent following wild-type adenovirus
      infection compared with hepatocytes transduced with control or Ad.RSV-gp19K
      recombinant adenovirus. This difference in surface MHC I down-regulation may be
      related to the different promoters (RSV-LTR versus the native E3 promoter) and
      will be an important consideration in the development of newer generation
      adenovirus vectors designed to evade host immune responses.

PMID- 9176524
TI  - Cloning of human IL-12 p40 and p35 DNA into the Semliki Forest virus vector:
      expression of IL-12 in human tumor cells.
AB  - IL-12 can enhance the development of effective immune responses against tumors as
      well as against certain infectious agents. It is therefore a potential candidate
      for therapeutic use in cancer therapy and in the design of vaccines against
      several infectious diseases. Several studies have demonstrated that IL-12 could
      efficiently induce tumor regression in animal models. To investigate the
      antitumor effect of direct gene transfer of human IL-12 into tumors, human IL-12
      p35 and p40 cDNAs were cloned into the Semliki Forest virus (SFV) vector pSFV1.
      In order to express the two subunits from the same vector, the p35 and the p40
      cDNAs were cloned into pSFV1, each under the control of a subgenomic SFV
      promoter. Recombinant RNA produced by in vitro transcription of SFV-IL-12
      construct, was packaged into SFV viral particles with the use of a non
      packageable helper RNA. We show that human tumor cell lines infected in vitro in
      vivo with recombinant SFV-IL-12 viral particles secrete high levels of
      biologically active heterodimeric p35/p40 IL-12, as demonstrated using ELISA and
      biological assays.

PMID- 9176525
TI  - Immunization with a plasmid expressing pneumococcal surface protein A (PspA) can
      elicit protection against fatal infection with Streptococcus pneumoniae.
AB  - Pneumococcal surface protein A (PspA) is a protectioneliciting protein of
      Streptococcus pneumoniae. We observed that immunization of BALB/c mice with a
      plasmid expressing PspA significantly protected the mice from lethal challenge
      with S. pneumoniae when compared to control mice that received injections of the
      plasmid vector alone. The plasmid construct expressing PspA has been designated
      pKSD2601. Mice immunized intramuscularly with pKSD2601 had a mean log of colony
      forming units of 2.67 +/- 0.25 pneumococci circulating in their blood at 24 h
      after challenge as compared with control mice that had a mean log of colony
      forming units of 4.95 +/- 0.59. Those mice with lower numbers of pneumococci
      subsequently survived the challenge. Given the quantitative nature and ultimate
      end point (ie live versus dead) our mouse model should be useful in working out
      optimum expression of bacterial genes for DNA immunization.

PMID- 9176526
TI  - Oedema and cor pulmonale revisited.

PMID- 9176527
TI  - Intrapleural streptokinase: the answer to community acquired pleural infection?

PMID- 9176528
TI  - Measuring the clinical impact of thoracic computed tomographic scanning.

PMID- 9176530
TI  - Renal functional reserve in patients with severe chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Renal functional reserve is the normal increase in renal blood flow
      after a protein load, and reduced or absent renal functional reserve is an early
      index of renal impairment. Renal blood flow is frequently reduced during acute
      oedematous exacerbations of chronic obstructive pulmonary disease (COPD). It is
      possible that patients with severe COPD in the stable state may have a reduced or
      absent renal functional reserve which could be a factor in oedema formation.
      METHODS: Sixteen stable patients with severe COPD and five normal controls were
      studied. The mean (SD) arterial oxygen and carbon dioxide tensions (PaO2, PaCO2)
      and forced expiratory volume in one second (FEV1) of patients with COPD were 8.1
      (1.04) kPa, 6.3 (0.69) kPa, and 0.74 (0.27) 1, respectively. The pulsatility
      index (PI), an index of renovascular resistance, was measured non-invasively by
      Doppler ultrasonography at baseline and at intervals after a protein load of 250
      g steak. RESULTS: The PI fell after the protein load in the normal subjects from
      1.04 (0.19) to 0.84 (0.17), mean difference 0.20, 95% confidence interval of
      difference (CI) 0.14 to 0.27, p < 0.001. In the COPD group there was no change;
      baseline PI = 1.04 (0.16), PI after protein load = 1.08 (0.19), mean difference =
      -0.04, 95% CI-0.11 to 0.04, p = NS. Six of the patients with COPD were
      normocapnic and 10 were hypercapnic (PaCO2 > or = 6.0 kPa). The normocapnic
      patients had no significant change in PI (baseline PI = 1.07 (0.15), PI after
      protein load = 1.01 (0.16), mean difference = 0.06, 95% CI -0.03 to 0.15) while
      in the hypercapnic patients the PI tended to rise (baseline PI = 1.03 (0.17), PI
      after protein load = 1.12 (0.21), mean difference = -0.09, 95% CI 0.18 to 0.007,
      p = 0.06). CONCLUSIONS: Renal haemodynamics were unchanged after a protein load
      in patients with severe COPD, suggesting that they had no renal functional
      reserve. This may be a factor in the development of oedema frequently seen in
      patients with severe COPD, particularly in hypercapnic patients.

PMID- 9176529
TI  - Effect of inhaled glucocorticoids on IL-1 beta and IL-1 receptor antagonist (IL-1
      ra) expression in asthmatic bronchial epithelium.
AB  - BACKGROUND: Accumulating evidence suggests that the cytokine network is central
      to the immunopathology of bronchial asthma and the existence of naturally
      occurring cytokine antagonists has added to this complexity. Upregulation of both
      interleukin 1 beta (IL-1 beta) and its naturally occurring receptor antagonist,
      interleukin 1 receptor antagonist (IL-1ra), has previously been observed on
      asthmatic bronchial epithelium compared with normal airways. METHODS: The effect
      of inhaled beclomethasone dipropionate (BDP) on asthmatic bronchial epithelial
      expression of IL-1 beta and IL-1ra was studied. Frozen bronchial biopsy specimens
      from nine asthmatic subjects receiving 1000 micrograms BDP daily for eight weeks
      and from six asthmatic subjects receiving matching placebo were stained with anti
      IL-1 beta and anti-IL-1ra antibodies. Hue-saturation-intensity (HSI) colour image
      analysis was used to quantify the brown immunoperoxidase reaction colour present
      on the bronchial epithelium. RESULTS: There was a significant twofold decrease in
      the epithelial expression of IL-1 beta after treatment with BDP but no
      significant change was seen in IL-1ra (P = 0.175). CONCLUSION: The selective
      inhibition of IL-1 beta, without effect on IL-1ra, provides a novel mechanism for
      the anti-inflammatory action of glucocorticosteroids.

PMID- 9176531
TI  - Randomised controlled trial of intrapleural streptokinase in community acquired
      pleural infection.
AB  - BACKGROUND: Standard treatment for pleural infection includes catheter drainage
      and antibiotics. Tube drainage often fails if the fluid is loculated by fibrinous
      adhesions when surgical drainage is needed. Streptokinase may aid the process of
      pleural drainage, but there have been no controlled trials to assess its
      efficacy. METHODS: Twenty four patients with infected community acquired
      parapneumonic effusions were studied. All had either frankly purulent/culture or
      Gram stain positive pleural fluid (13 cases; 54%) or fluid which fulfilled the
      biochemical criteria for pleural infection. Fluid was drained with a 14F
      catheter. The antibiotics used were cefuroxime and metronidazole or were guided
      by culture. Subjects were randomly assigned to receive intrapleural
      streptokinase, 250,000 i.u. daily, or control saline flushes for three days. The
      primary end points related to the efficacy of pleural drainage--namely, the
      volume of pleural fluid drained and the chest radiographic response to treatment.
      Other end points were the number of pleural procedures needed and blood indices
      of inflammation. RESULTS: The streptokinase group drained more pleural fluid both
      during the days of streptokinase/control treatment (mean (SD) 391 (200) ml versus
      124 (44) ml; difference 267 ml, 95% confidence interval (CI) 144 to 390; p <
      .001) and overall (2564 (1663) ml, 95% CI 465 to 2545; p < 0.01). They showed
      greater improvement on the chest radiograph at discharge, measured as the fall in
      the maximum dimension of the pleural collection (6.0 (2.7) cm versus 3.4 (2.7)
      cm; difference 2.9 cm, 95% CI 0.3 to 4.4; p < 0.05) and the overall reduction in
      pleural fluid collection size (p < 0.05, two-tailed Fisher's exact test).
      Systemic fibrinolysis and bleeding complications did not occur. Surgery was
      required by three control patients but none in the streptokinase group.
      CONCLUSIONS: Intrapleural streptokinase probably aids the treatment of pleural
      infections by improving pleural drainage without causing systemic fibrinolysis or
      local haemorrhage.

PMID- 9176532
TI  - Transmission of Pneumocystis carinii from patients to hospital staff.
AB  - BACKGROUND: An extrahuman reservoir of human pathogenic Pneumocystis carinii
      remains unknown. Host to host transmission has been described in animal studies
      and in cluster cases among immunodeficient patients. P carinii DNA has recently
      been detected in air filters from inpatient and outpatient rooms in departments
      of infectious diseases managing patients with P carinii pneumonia (PCP),
      suggesting the airborne route of transmission. Exposure of staff to P carinii may
      occur in hospital departments treating patients with PCP. METHODS: Exposure to P
      carinii was detected by serological responses to human P carinii by ELISA,
      Western blotting, and indirect immunofluorescence in 64 hospital staff with and
      79 staff without exposure to patients with PCP from Denmark and Sweden. DNA
      amplification of oropharyngeal washings was performed on 20 Danish staff with and
      20 staff without exposure to patients with PCP. RESULTS: There was no significant
      difference in the frequency or level of antibodies to P carinii between staff
      exposed and those unexposed to patients with PCP. None of the hospital staff had
      detectable P carinii DNA in oropharyngeal washings. CONCLUSIONS: There is no
      difference in antibodies and no detectable P carinii DNA in oropharyngeal
      washings, which suggests that immunocompetent staff treating patients with PCP
      are not a potentially infectious source of P carinii for immunocompromised
      patients.

PMID- 9176533
TI  - Assessment of fitness in patients with cystic fibrosis and mild lung disease.
AB  - BACKGROUND: Maximal exercise testing is used in patients with cystic fibrosis to
      assess functional status and prognosis. The lactate threshold is an index of
      aerobic fitness with significant advantages over maximal exercise tests. This
      study was undertaken to determine if the lactate threshold might be identified,
      non-invasively, in adult patients with cystic fibrosis and mild lung disease by
      measurement of ventilatory and gas exchange parameters. METHODS: Ten subjects
      with mild cystic fibrosis (forced vital capacity (FVC) > 70% predicted) and 10
      healthy controls undertook an incremental exercise test on a bicycle ergometer.
      Ventilation and gas exchange parameters were measured continually and
      arterialised venous blood pH, carbon dioxide tension (PCO2), and lactate
      concentrations were measured at intervals throughout the tests. RESULTS: In
      subjects with cystic fibrosis there was no significant difference between the
      mean gas exchange and lactate thresholds (mean difference 1.0 (95% confidence
      interval (CI) of the mean -1.5 to 3.44) ml/kg/min). In contrast, there was a
      significant difference between the mean ventilatory and lactate thresholds (3.8
      (95% CI 0.9 to 6.7) ml/kg/min). Arterialised venous PCO2 increased significantly
      during the exercise tests. In healthy subjects the mean differences between these
      thresholds were not significantly different from zero and PCO2 fell significantly
      during the tests. CONCLUSIONS: The ventilatory threshold significantly
      overestimates the lactate threshold in subjects with cystic fibrosis induced lung
      disease because of impaired carbon dioxide excretion during exercise. However,
      the gas exchange threshold may be used to determine the lactate threshold in this
      patient group.

PMID- 9176534
TI  - Analysis of T cell subsets and beta chemokines in patients with pulmonary
      sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disorder of unknown origin
      characterised by accumulation of T lymphocytes and macrophages in multiple
      organs. Several cytokines and adhesion molecules may contribute to the
      accumulation of T lymphocytes in pulmonary sarcoidosis. The distribution of T
      lymphocyte subsets, T cell bearing CD11a and beta chemokines such as regulated on
      activation normal T expressed and secreted (RANTES), macrophage inflammatory
      peptide 1 alpha (MIP-1 alpha), and macrophage chemoattractant protein 1 (MCP-1)
      in bronchoalveolar lavage (BAL) fluid and peripheral blood were compared in
      untreated patients with sarcoidosis and normal subjects. METHODS: Flow cytometric
      analysis with monoclonal antibodies to cell surface antigens was used to identify
      T lymphocyte subsets in the BAL fluid of untreated patients with sarcoidosis (n =
      40)--either without (group A, n = 12) or with (group B, n = 28) radiological
      evidence of pulmonary involvement--and in 22 normal subjects. The level of
      different beta chemokines was estimated by enzyme linked immunosorbent assay
      (ELISA). RESULTS: A high percentage of CD3+ cells, CD4+ cells expressing HLA-DR
      antigen, and a high CD4/CD8 ratio were detected in the BAL fluid of patients
      compared with normal subjects. In particular, CD4+ CD29+ memory T cells were
      significantly increased in patients with sarcoidosis. Furthermore, these cells
      were higher in those in group B than group A. The level of RANTES in the BAL
      fluid of patients was significantly higher than in normal subjects and correlated
      well with the percentage, number, and expression of CD29 on CD4 cells. The
      expression of CD11a (alpha chain of lymphocyte function associated antigen-1, LFA
      1) on CD3+ cells in the BAL fluid of patients with sarcoidosis was not different
      from that of normal subjects. However, the expression of CD11a on CD3+ cells in
      the BAL fluid of patients in group A was significantly lower than that of
      patients in group B and normal subjects. CONCLUSIONS: These results suggest a
      possible interaction between activated memory T cells bearing CD11a and RANTES
      which may contribute to the pulmonary involvement in patients with sarcoidosis.

PMID- 9176535
TI  - Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron
      emission tomography (PET).
AB  - BACKGROUND: A study was undertaken to investigate the accuracy of positron
      emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in the
      thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty
      six patients with focal pulmonary tumours who underwent preoperative computed
      tomographic (CT) and FDG-PET scanning were evaluated retrospectively. Thirty two
      patients had NSCLC and 14 patients had a benign process. The final diagnosis was
      established by means of histopathological examination at thoracotomy, and the
      nodal classification in patients with lung cancer was performed by thorough
      dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80%
      sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in
      patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and
      59.4% accurate. The absence of lymph node tumour involvement was identified by
      FDG-PET in all 12 patients with NO disease compared with nine by CT scanning.
      Lymph node metastases were correctly detected by FDG-PET in three of five
      patients with N1 disease compared with two by CT scanning, in nine of 11 with N2
      disease compared with six by CT scanning, an in all four with N3 nodes compared
      with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method
      for staging thoracic lymph nodes in patients with lung cancer and is superior to
      CT scanning in the assessment of hilar and mediastinal nodal metastases. With
      regard to resectability, FDG-PET could differentiate reliably between patients
      with N1/N2 disease and those with unresectable N3 disease.

PMID- 9176536
TI  - Relative production of tumour necrosis factor alpha and interleukin 10 in adult
      respiratory distress syndrome.
AB  - BACKGROUND: The adult respiratory distress syndrome (ARDS) may be regarded as an
      example of an uncontrolled or excessive inflammatory response in which tumour
      necrosis factor alpha (TNF-alpha) has been proposed to play a central role.
      Interleukin 10 (IL-10) has been identified as an important regulator of this
      response. The potential role for IL-10 in this context was investigated by
      measuring the relative production of IL-10 and TNF-alpha protein in the plasma,
      bronchoalveolar lavage (BAL) fluid, and alveolar macrophage culture supernatants
      of patients with, or at risk of developing, ARDS. METHODS: Twenty six patients
      were studied from three groups at risk of or with ARDS: sepsis (n = 12), multiple
      trauma (n = 8), and perforated bowel (n = 6). Ten patients had ARDS.
      Bronchoalveolar lavage and venepuncture were performed within 24 hours of arrival
      on the intensive therapy unit or of diagnosis of ARDS. IL-10 and TNF-alpha
      protein were detected in the plasma, BAL fluid, and alveolar macrophage
      supernatants by sandwich enzyme linked immunoabsorbent assays. RESULTS: The
      median IL-10 concentrations in the plasma and BAL fluid of patients with ARDS
      were significantly lower than the concentrations detectable in the plasma (median
      difference-17.5, 95% CI -52.4 to 1.31, p < 0.05) and BAL fluid of at risk
      patients (median difference -32.1, 95% CI -47.5 to 2.3, p < 0.05). There was a
      tendency towards enhanced concentrations of TNF-alpha detectable in the alveolar
      macrophage supernatants and the BAL fluid of patients with ARDS compared with at
      risk patients, although this did not reach statistical significance. No
      difference was observed in the plasma concentrations of TNF-alpha between the two
      groups. The ratios of TNF-alpha to IL-10 protein in the BAL fluid of patients
      with ARDS and at risk patients were 3.52 and 0.85, respectively (median
      difference 1.44, 95% CI 0.07 to 5.01, p < 0.01). There was no difference in
      alveolar macrophage production of IL-10 between the two groups. CONCLUSIONS: This
      study highlights the potential importance of the pro-inflammatory versus the anti
      inflammatory imbalance in ARDS which may be reflected by the ratio of IL-10 and
      TNF-alpha in the lung.

PMID- 9176537
TI  - Effect of cyclosporin A on the allergen-induced late asthmatic reaction.
AB  - BACKGROUND: The allergen-induced late asthmatic reaction (LAR) is associated with
      mucosal inflammation involving several cell types including activated T
      lymphocytes and eosinophils. In contrast, the early asthmatic reaction (EAR) is
      considered to results from rapid allergen-induced release of bronchoconstrictor
      mediators from IgE sensitised mast cells. Cyclosporin A has efficacy in chronic
      severe corticosteroid-dependent asthma and is believed to act principally by
      inhibiting cytokine mRNA transcription in T lymphocytes. However, it has effects
      on other cell types in vitro, including the inhibition of
      exocytosis/degranulation events in mast cells. It was therefore hypothesised that
      cyclosporin A would attenuate both the EAR and LAR in subjects with mild asthma.
      METHODS: Twelve sensitised atopic asthmatic subjects with documented dual
      asthmatic responses were studied in a double blind, placebo controlled, crossover
      trial. On two separate study visits subjects received two oral doses of either
      cyclosporin A or matched placebo before inhaled allergen challenges. The forced
      expiratory volume in one second (FEV1) was measured half hourly for eight hours
      and blood eosinophil counts were analysed three, six, and 24 hours after the
      challenge. Treatment effects on blood eosinophil counts as well as the EAR and
      LAR, respectively defined as the areas under the curve (AUC) of FEV1 changes from
      baseline between 0-1 and 4-8 hours after challenge, were compared by non
      parametric crossover analysis. RESULTS: Cyclosporin A reduced both the LAR
      (median AUC -41.9 1.h (interquartile range -82.7 to -12.4) for cyclosporin A and 
      84.5 1.h (-248.9 to -39.1) for placebo; p = 0.007) and the late increase in blood
      eosinophils (median 0.2 x 10(9)/1 (0.15 to 0.4) for cyclosporin A and 0.4 x
      10(9)/1 (0.25 to 0.55) for placebo; p = 0.024) but had no effect on the EAR. The
      reduction of the LAR by cyclosporin A correlated significantly with prechallenge
      blood concentrations of cyclosporin A (r = 0.6, p = 0.028). CONCLUSIONS: These
      data are consistent with the concept that cyclosporin A has anti-inflammatory
      actions in asthma resulting from inhibition of mRNA transcription of eosinophil
      active cytokines, predominantly in T lymphocytes. Cyclosporin A, possibly in its
      inhaled form, or other agents which prevent cytokine gene transcription may
      therefore have potential in ameliorating the inflammatory component of asthma.

PMID- 9176538
TI  - Effect of acute alterations in inspired oxygen tension on methacholine induced
      bronchoconstriction in patients with asthma.
AB  - BACKGROUND: Recent in vitro and in vivo studies in animals have suggested that
      ambient oxygen tension may influence airway responsiveness to bronchoconstrictor
      stimuli. These observations may have relevance to the management of acute
      exacerbations of asthma. The present studies were designed to examine the
      influence of inspired oxygen tension (Fio2 1.0, 0.21, 0.15) on methacholine
      induced broncho-constriction in patients with asthma. METHODS: In a dual study
      two groups of asthmatic patients performed methacholine inhalation challenges
      breathing either air (Fio2 0.21) or a hypoxic gas mixture (Fio2 0.15) in study 1
      and air (Fio2 0.21) or hyperoxia (Fio2 1.0) in study 2. The gases were
      administered through a closed breathing circuit in a randomised double blind
      fashion. The PC20 values (dose of methacholine causing a 20% fall in forced
      expiratory volume in one second (FEV1) were calculated after each methacholine
      challenge by linear interpolation from the logarithmic dose response curve.
      Plasma catecholamine levels were measured before and after methacholine
      challenges as well as heart rate, oxygen saturation, and percentage end tidal
      carbon dioxide levels. RESULTS: The geometric mean PC20 value for methacholine
      was significantly lower on the hypoxic study day than on the normoxic day in
      study 1 (mean difference in PC20 values 2.88 mg/ml (95% CI 1.4 to 5.3); p <
      0.05), but there was no significant difference in the geometric mean PC20 value
      for methacholine between the hyperoxic and normoxic study days in study 2 (mean
      difference in PC20 values 1.45 mg/ ml (95% CI 0.83 to 2.51)). CONCLUSIONS: Acute
      hypoxia potentiates methacholine induced bronchoconstriction and acute hyperoxia
      has no effect in mild to moderate patients with stable asthma.

PMID- 9176539
TI  - Time course and relative dose potency of systemic effects from salmeterol and
      salbutamol in healthy subjects.
AB  - BACKGROUND: The main adverse effects of beta 1 agonists relate to their systemic
      activity. The time course and dose response relations of the systemic effects of
      salmeterol compared with salbutamol were investigated. METHODS: A double blind,
      randomised, crossover study was carried out in 14 healthy subjects who attended
      on seven days. Heart rate, QTc interval, blood pressure, plasma potassium and
      glucose concentrations were measured for four hours following inhaled placebo,
      salmeterol 100, 200 and 400 micrograms and salbutamol 600, 1200 and 2400
      micrograms given by metered dose inhaler. Maximum changes from baseline and
      maximum absolute values following each dose of treatment were used to construct
      log dose response curves and calculate relative dose potency. RESULTS: Both
      salmeterol and salbutamol caused dose dependent changes in heart rate, QTc
      interval, and plasma potassium and glucose concentrations. The onset of cardiac
      effects was rapid following both drugs, whereas changes in glucose and potassium
      concentrations occurred more gradually with salmeterol. The increase in heart
      rate and fall in potassium level were sustained over the four hours whereas
      glucose levels gradually returned towards baseline. The relative dose potency of
      salmeterol compared with salbutamol for changes from baseline was 7.1 (95% CI 3.9
      to 14.4) for the QTc interval and 8.2 (95% CI 5.7 to 12.6) for plasma potassium
      concentration. Salmeterol caused steeper dose response curves for heart rate and
      plasma glucose concentration than salbutamol so relative dose potency values
      could not be calculated. CONCLUSIONS: These findings support previous data that
      salmeterol 100 micrograms is broadly equivalent to salbutamol 800 micrograms for
      systemic effects. The greater systemic effects of salmeterol are most likely to
      be due to greater potency relative to dose, although it may also have greater
      systemic bioavailability. The steeper dose response curve for heart rate with
      salmeterol indicates that it has a narrower therapeutic window than salbutamol
      and thus should be prescribed at the lowest effective dose.

PMID- 9176540
TI  - Involvement of an NAD(P)H oxidase-like enzyme in superoxide anion and hydrogen
      peroxide generation by rat type II cells.
AB  - BACKGROUND: Although alveolar macrophages are considered to be the primary
      cellular mediators of host defence in the lung, there is increasing evidence that
      type II cells may also play an active role in host defence. A study was
      undertaken to investigate whether type II cells generate O2-. and H2O2 via an
      NADPH oxidase-like system and whether exposure of the type II cells to soluble or
      particulate stimuli known to activate NADPH oxidase in macrophages also leads to
      increased production of H2O2. METHODS: Rat type II cells and alveolar macrophages
      were exposed to 10, 100, or 1000 nM phorbol-12-myristate-13-acetate (PMA) and the
      production of O2-. and H2O2 was determined by chemiluminescence. Thirty minutes
      before stimulation with 1 microM PMA type II cells were also exposed to the same
      concentrations of a protein kinase C (PKC) antagonist GF109203x, the non
      selective protein kinase inhibitor staurosporine (1, 10, or 100 nM), or the NADPH
      oxidase inhibitor diphenyliodonium chloride (DPI) (1, 10, 100, or 1000 microM).
      The effects of arachidonic acid, zymosan and Staphylococcus aureus on H2O2
      production were determined. Cell membrane fractions from type II cells and
      macrophages were assayed for NADPH oxidase activity. RESULTS: After exposure to 1
      microM PMA, O2-. and H2O2 generation increased 6.3-fold and 9.0-fold,
      respectively, in type II cells and 2.4-fold and 5.2-fold, respectively, in
      macrophages. In contrast to the macrophages, the increase in O2-. and H2O2
      generation by type II cells was completely prevented by 1 mM KCN. Preexposure to
      GF109203x, staurosporine, or DPI completely prevented the rise in O2-. and H2O2
      generation. Mean (SD) NADPH oxidase activity of 138 (38) nmol O2-./min/mg protein
      was found in membrane fraction I of the type II cells, and 102 (31) nmol O2
      ./min/mg protein in fraction II. Macrophages showed higher NADPH oxidase activity
      in membrane fraction II. In type II cells exposure to arachidonic acid led to a
      significant 5.3-fold increase in H2O2 generation, exposure to zymosan increased
      H2O2 generation 46-fold, and exposure to S aureus 25-fold with a maximum 30-50
      minutes after addition of the bacteria. CONCLUSIONS: Type II cells generate O2-.
      and H2O2 via a PKC-mediated activation of an NAD(P)H oxidase-like membrane bound
      enzyme. Arachidonic acid, zymosan, and bacteria also give rise to increased H2O2
      production. Type II cells might thus play an active role in host defence.

PMID- 9176541
TI  - Diaphragm thickness and inspiratory strength in patients with Duchenne muscular
      dystrophy.
AB  - BACKGROUND: There is little information on the morphometric characteristics of
      the diaphragm in patients with Duchenne muscular dystrophy. METHODS: The
      thickness of the diaphragm was measured at the zone of apposition using B mode
      ultrasonography in 10 boys with Duchenne muscular dystrophy of mean (SD) age 10.3
      (1.3) years and 12 normal controls of mean (SD) age 11.3 (2.0) years during
      relaxation (DiTrelax) and during maximum effort inspiratory manoeuvres (DiTPimax)
      at functional residual capacity. RESULTS: DiTrelax was greater in the patients
      with Duchenne muscular dystrophy (1.74 (0.21) mm) than in controls (1.48 (0.20)
      mm), mean difference (95% CI) 0.26 (0.08 to 0.44), despite considerable
      impairment of maximum effort inspiratory mouth pressure (Pimax) (patients with
      Duchenne muscular dystrophy -37 (8) cm H2O, controls -80 (33) cm H2O), mean
      difference (95% CI) 43 (65 to 20). During a Pimax manoeuvre, compared with
      measurements taken during relaxation, the diaphragm thickened 1.6 times in
      patients with Duchenne muscular dystrophy and 2.3 times in controls (DiTPimax
      2.62 (0.7) mm and 3.5 (0.85) mm, respectively), mean difference (95% CI) -0.88 (
      1.58 to -0.18). CONCLUSIONS: Resting diaphragm thickness is increased in young
      patients with Duchenne muscular dystrophy with impaired respiratory muscle force.
      This finding could be analogous to the pseudo-hypertrophy that is observed in
      some limb muscle groups.

PMID- 9176542
TI  - Measures for detecting systemic bioactivity with inhaled and intranasal
      corticosteroids.

PMID- 9176543
TI  - Anti-interleukin 5 strategies as a potential treatment for asthma.
AB  - A paradigm shift, championed largely by cellular immunologists, has redefined
      asthma as an immune mediated phenomenon characterised by an interleukin 5 (IL-5)
      driven eosinophilic bronchitis. This change in emphasis has provoked intense
      interest in the possibility that inhibitors of IL-5 production, or antagonists of
      its activity, will provide a new generation of anti-asthma drugs.

PMID- 9176544
TI  - Management of oesophageal atresia.

PMID- 9176545
TI  - Oesophageal plastic repair for symptomatic ballooning following circular
      oesophageal myotomy and correction of oesophageal atresia.
AB  - Two patients with refractory anastomotic stenosis and symptomatic ballooning of
      the upper oesophageal pouch following repair of long gap oesophageal atresia are
      described. In both cases a circular myotomy had been used to elongate the
      proximal oesophageal segment at the time of primary repair. Both patients were
      successfully treated by Y-V plasty of the oesophageal stenosis and tailoring of
      the dilated segment.

PMID- 9176547
TI  - Accessory cardiac bronchus presenting with haemoptysis.

PMID- 9176546
TI  - An unusual case of flail chest: surgical repair using Marlex mesh.
AB  - The case history is presented of a patient with neurofibromatosis with a chest
      wall defect present from birth. Abnormal rib development had resulted in a flail
      segment with painful paradoxical movement and unsightly costal cartilage
      protrusion. Chest wall reconstruction using Marlex mesh resulted in an excellent
      cosmetic and functional repair.

PMID- 9176550
TI  - Sputum differential cell counts.

PMID- 9176548
TI  - Superior vena cava syndrome associated with Nocardia farcinica infection.
AB  - A case is described of severe Nocardia farcinica infection which mimicked a
      pulmonary neoplasm with pneumonia, superior vena cava syndrome, pericarditis, and
      hypertrophic osteoarthropathy. Treatment with trimethoprim-sulphamethoxazole and
      surgery resulted in complete recovery.

PMID- 9176549
TI  - Effect of altitude on children with asthma.

PMID- 9176552
TI  - Attitudes toward environmental hazards: where do toxic wastes fit?
AB  - The public is continually faced with making decisions about the risks associated
      with environmental hazards, and, along with managers and government officials,
      must make informed decisions concerning possible regulation, mitigation, and
      restoration of degraded sites or other environmental threats. We explored the
      attitudes regarding several environmental hazards of six groups of people:
      undergraduate science majors, undergraduate nonscience majors, and graduate
      students in environmental health, in ecological risk assessment, and in
      nonscience disciplines, as well as nonstudents over 35 yr of age. We had
      predicted that there would be significant differences in attitudes between
      science and nonscience majors and as a function of age. Relative concerns could
      be divided into three discrete classes (in descending order of concern): (1)
      general ecological problems (cutting tropical forests, polluting groundwater,
      trash along the coasts, lead in drinking water, and acid rain), (2) radon and
      nuclear wastes, and finally (3) specific nuclear waste facilities, chromium,
      fertilizers and pesticides, and electromagnetic waves. For any hazard, attitudes
      were consistent across groups with regard to ranking the severity of the
      environmental problem and willingness to expend funds to solve the problems.
      Attitudes about spending money to develop methods to evaluate risk fell in the
      middle level of concern. There were no major differences among classes of college
      age students, or between them and older nonstudents.

PMID- 9176551
TI  - Bioavailability of TNT residues in composts of TNT-contaminated soil.
AB  - Composting is being explored as a means to remediate 2,4,6-trinitrotoluene (TNT)
      contaminated soils. This process appears to modify TNT and to bind it to organic
      matter. The health hazards associated with dusts generated from such materials
      cannot be predicted without knowing if the association between TNT residues and
      compost particulate is stable in biological systems. To address this question,
      single doses of [14C]-TNT, soil spiked with [14C]-TNT, or compost generated with
      [14C]-TNT-spiked soils were administered to rats by intratracheal instillation.
      The appearance of 14C in urine and tissues was taken as an indication of the
      bioavailability of TNT residues from compost particles. In rats instilled with
      neat [14C]-TNT, about 35% of the 14C dose appeared in urine within 3 d. The 14C
      excreted in urine by these rats decreased rapidly thereafter, and was
      undetectable by 4 wk after treatment. Similar results were obtained with soil
      treated rats. In contrast, after treatment with [14C]-TNT-labeled compost, only
      2.3% of the total 14C dose appeared in urine during the first 3 d. Low levels of
      14C continued to be excreted in urine from compost-treated rats for more than 6
      mo, and the total amount of 14C in urine was comparable to that in TNT-treated
      animals. Determination of the radiolabel in tissues showed that 14C accumulated
      in the kidneys of rats treated with labeled compost but not in rats treated with
      [14C]-TNT or [14C]-TNT-spiked soil. These results indicate that the association
      between TNT and particulate matter in compost is not stable when introduced into
      the lungs. Accumulation of 14C in kidneys suggests the presence of a unique TNT
      residue in compost-treated rats. The rate of excretion and tissue disposition of
      14C in rats treated with TNT-spiked soil indicate that TNT in soil is freely
      available in the lungs.

PMID- 9176553
TI  - Mercury content in skin-lightening creams and potential hazards to the health of
      Saudi Women.
AB  - It seems evident from a wealth of scientific research that mercury is toxic.
      Because of the nature of the Saudi markets, different brands of skin-lightening
      creams are widely available. In this study, 38 skin-lightening cream samples were
      collected and analyzed for mercury by inductively coupled plasma spectrometry
      after an acid digestion procedure. About 45% of the tested skin-lightening cream
      samples contained mercury at levels well above the FDA's acceptable limit of 1
      ppm. These findings are alarming and have wide legal and educational implications
      for Saudi Arabia in particular and developing countries in general. Further
      investigation for possible adverse health effects is also needed.

PMID- 9176555
TI  - Activity of esterases from different tissues of freshwater fish and responses of
      their isoenzymes to inhibitors.
AB  - Activity of nonspecific esterase from different tissues (i.e., liver,
      gallbladder, heart, intestine, and muscle) of five species of freshwater fish,
      namely, topmouth gudgeon (Pseudorasbora parva), goldfish (Carassius auratus),
      nile tilapia (Tilapia nilotica), mosquitofish (Gambusia affinis), and rainbow
      trout (Salmo gairdneri) was tested using alpha-naphthyl acetate as substrate. The
      results indicated that activity of the enzyme was mainly concentrated in the
      digestive system (i.e., intestine, liver, bile). The overall activity was highest
      in nile tilapia, followed by mosquitofish, topmouth gudgeon, goldfish, and lowest
      in rainbow trout. Electrophoresis and the following in vitro treatment of the
      isoenzymes with triphenol phosphate (TPP, an inhibitor of carboxylesterase)
      indicated the TPP-sensitive esterase was mainly distributed in liver of the five
      species. The enzyme was not found in the other five tissues (including gill)
      except in gallbladder of topmouth gudgeon and goldfish. The correlation was
      obviously improved between susceptibility and detoxification capacity if activity
      of the TPP-sensitive esterase was employed instead of that of the nonspecific
      esterase to make the comparison. In vitro treatment of nonspecific esterase in
      liver with malaoxon proved that the active metabolite of malathion inhibited a
      different isoenzyme from the TPP-sensitive one.

PMID- 9176554
TI  - Tributyltin potentiates 3,3',4,4',5-pentachlorobiphenyl-induced cytochrome P
      4501A-related activity.
AB  - Induction of cytochrome P-4501A protein and induction of related enzyme activity
      are hallmark physiological responses following exposure to planar halogenated
      aromatic hydrocarbons (HAHs) such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126;
      PeCB). Environments contaminated by HAHs are often contaminated by mixtures of
      anthropogenic contaminants, including organometallic compounds. Both HAHs and
      organometallics easily bioconcentrate and bioaccumulate in aquatic food chains
      that may ultimately be linked to humans through seafood consumption. Tributyltin
      (TBT), a marine biocide, has been detected in many aquatic environments due to
      its primary use as a marine antifoulant agent. Exposure to TBT, as well as
      several PCBs, has been associated with immunotoxicity, neurotoxicity, and
      endocrine disruption. Recently TBT has been shown to inhibit cytochrome P-4501A
      activity in vitro, but information concerning these effects in vivo and in
      combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed
      female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBT, or both in combination,
      with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein
      levels and related benzo[a]pyrene hydroxylation (BaP-OHase) activity were
      measured following a single acute intraperitoneal (ip) dose or seven daily
      injections. Body, thymus, and liver weights were used to monitor general
      physiological responses following exposure. P-4501A levels and BaP-OHase activity
      were significantly elevated in mice exposed to PeCB alone. This effect was
      enhanced by coexposure to low levels of TBT; PeCB-induced P-4501A-related
      activity was potentiated at the low range of each. The highest dose of TBT,
      however, inhibited these activities when given in combination with PeCB. Thymic
      atrophy was evident only in mice exposed daily to 0:1 and 1.0 mg/kg PeCB alone,
      or to a combination of the lowest and highest dose of PeCB and TBT, respectively.
      Because environmental levels of TBT are not expected to be as high as the highest
      level used in our toxicological studies, we conclude that environmental exposure
      to TBT may potentiate, rather than inhibit, the activity of environmental levels
      of HAHs that are associated with P-4501A induction.

PMID- 9176556
TI  - Effects of malathion metabolites on degranulation of and mediator release by
      human and rat basophilic cells.
AB  - In the present study, the effects of malathion and malathion derivatives on
      histamine and beta-hexosaminidase release by RBL-1 cells, rat peritoneal mast
      cells (RPMC), and human peripheral blood basophils (HPBB) and cutaneous mast
      calls were examined. One hour of incubation of RBL-1 cells with all
      organophosphate compounds tested, except for malathion and malathion monoacid,
      led to an increase in histamine release. beta-Hexosaminidase, an enzyme released
      by basophilic cells and a biochemical marker of degranulation, was not released
      from RBL-1 cells after 1 h of exposure to organophosphate compounds. Within 4 h,
      all compounds tested increased the release of histamine and beta-hexosaminidase.
      Longer exposures led to a decrease in the concentration of the compound that was
      required to cause mediator release. Exposure of RPMC to organophosphate
      compounds, with the exception of malathion monoacid and malathion (30 min) or
      malathion monoacid (1 h), led to the release of histamine, but not beta
      hexosaminidase. Incubation of HPBB with malaoxon (51.4 +/- 2.8% total histamine
      released), malathion diacid (25.7 +/- 2.9%), beta-malathion monoacid (31.4 +/-
      2.8%), and isomalathion (57.1 +/- 17.1%) for 1 h led to the release of histamine.
      Only malaoxon and isomalathion caused beta-hexosaminidase release from HPBB after
      a 1-h incubation. Incubation of cutaneous mast cells with malaoxon and beta
      monoacid for 4 h led to increased release of histamine and beta-hexosaminidase at
      levels comparable to compound 48/80. These data suggest that malathion
      metabolites can cause rapid release of histamine from basophilic cells from a
      variety of origins and species. With prolonged incubation, malathion itself
      caused the release of mast-cell mediators, suggesting that the cells may be
      capable of metabolizing malathion. These data also indicate a disparity between
      the release kinetics of two different mast-cell mediators contained in granules
      by organophosphates, and that there are different mechanisms of mediator release.

PMID- 9176557
TI  - Comparison of mouse strains for susceptibility to styrene-induced hepatotoxicity
      and pneumotoxicity.
AB  - Styrene is known to cause both hepatotoxicity and pneumotoxicity in mice. Strain
      differences have been reported by other investigators suggesting that Swiss mice
      are less susceptible than non-Swiss mice to styrene-induced liver damage. In this
      study, A/J and C57BL/6 mice were found to be similar to non-Swiss albino (NSA)
      mice in susceptibility whereas CD-1 (Swiss) mice were more resistant to
      hepatotoxicity as assessed by serum sorbitol dehydrogenase levels and
      pneumotoxicity as determined by gamma-glutamyltranspeptidase and lactate
      dehydrogenase measurements in bronchoalveolar lavage fluid. Styrene was
      hepatotoxic in CD-1 mice treated with pyridine to induce CYP2E1. CYP2E1
      apoprotein levels and p-nitrophenol hydroxylase activities in control and
      pyridine-induced mice were similar in the two strains. Hepatic and pulmonary
      microsomal preparations from both strains metabolized styrene to styrene oxide at
      similar rates. CD-1 mice were as susceptible as the NSA mice to the effects of
      styrene oxide. The data suggest that there are no differences in the
      bioactivation of styrene to styrene oxide or innate susceptibility to the active
      metabolite that would account for the differences between the CD-1 and NSA mice.

PMID- 9176558
TI  - Reduction of the ex vivo production of tumor necrosis factor alpha by alveolar
      phagocytes after administration of coal fly ash and copper smelter dust.
AB  - We investigated the effect of intratracheally instilled coal fly ash (FA) and
      copper smelter dust (CU) on the lung integrity and on the ex vivo release of
      tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Groups of female
      NMRI mice received a single intratracheal administration of different particles
      normalized for the arsenic content (20 micrograms/kg body weight, i.e., 600 ng
      arsenic/mouse) and the particle load (100 mg/kg body weight, i.e., 3 mg/mouse).
      Mice received tungsten carbide (WC) alone (100 mg/kg), FA alone (100 mg/kg, i.e.,
      20 micrograms arsenic/kg), CU mixed with WC (CU, 13.6 mg/kg, i.e., 20 micrograms
      arsenic/kg; WC, 86.4 mg/kg) and Ca3(AsO4)2 mixed with WC (20 micrograms
      arsenic/kg; WC, 100 mg/kg). Animals were sacrificed at 1, 6, or 30 d
      posttreatment and analyzed by bronchoalveolar lavage for total protein (TP)
      content, inflammatory cell number and type, and TNF-alpha production. Additional
      mice were studied to evaluate particle retention by measuring total arsenic
      retention in the lung at appropriate times. Instillation of WC induced a mild and
      transient (d 1) inflammatory reaction characterized by an increase of TP and an
      influx of polymorphonuclear leukocytes in the alveolar compartment. Compared to
      WC, Ca3(AsO4)2 produced a significant increase of TP content in BALF. CU
      particles caused a severe but transient inflammatory reaction, while a persisting
      alveolitis (30 d) was observed after treatment with FA. Compared to control
      saline, a marked inhibition of TNF-alpha release was observed in response to LPS
      in all groups at d 1. Cytokine production was upregulated in WC- and Ca3(AsO4)1
      treated animals after 6 and 30 d, respectively. However, a 90% inhibition of TNF
      alpha production was still observed at d 30 after administration of CU and FA.
      Although arsenic was cleared from the lung tissue 6 d after Ca3(AsO4)2
      administration, a significant fraction persisted (10-15% of the arsenic
      administered) in the lung of CU- and FA-treated mice at d 30. We hypothetize that
      suppression of TNF-alpha production is dependent upon the slow elimination of the
      particles and their metal content from the lung.

PMID- 9176560
TI  - Signal transduction in the retina and inherited retinopathies.
AB  - In this paper, an attempt is made to highlight some of the recent developments in
      genetics to understand the group of inherited eye disorders referred to as
      retinitis pigmentosa (RP). Of the seven genes identified, six are expressed
      specifically in the photoreceptor cells and four encode the enzymes involved in
      the phototransduction pathway. A short discussion is presented of the tremendous
      phenotypic heterogeneity. An understanding of RP requires knowledge of other
      genetic and environmental factors as well as tests to measure the status of the
      patient's photoreceptor cells in various disease stages.

PMID- 9176561
TI  - Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus.
AB  - We investigated whether the administration of melatonin (MLT) reduces the death
      rate and evolution of the disease in mice infected with Venezuelan equine
      encephalomyelitis (VEE) virus. Our results show that, MLT protects mice infected
      with the virus. The mortality rate was reduced from 100% to 16% merely by
      increasing the dose from 0 to 1000 micrograms/MLT per kg body weight MLT
      significantly postponed the onset of the disease and death by several days. In
      surviving mice very high titres of VEE virus IgM antibodies were found seven
      weeks after virus inoculation. MLT significantly reduced VEE virus levels in
      blood and brain of infected mice and increased the survival rate when the length
      of pretreatment was augmented from 3 to 7 or 10 days before virus inoculation.
      Serum levels of interleukin-2 were not affected by MLT administration. In control
      mice receiving MLT as well as in infected mice treated or non-treated with MLT,
      interferon gamma levels in sera were increased. Interleukin-4 concentrations were
      found to be elevated in sera of non-infected mice receiving MLT, but did not
      differ from controls in infected mice treated or non-treated with the hormone.
      MLT reduced the degree of cell destruction produced by VEE virus in culture
      plates of chicken embryo fibroblasts. The protective effect of MLT warrants
      further investigation of the possibility of using this hormone for the treatment
      of humans and equines infected with VEE virus.

PMID- 9176559
TI  - The effect of paclitaxel on the radiosensitivity of gynecological tumor cells.
AB  - BACKGROUND: Paclitaxel, a natural product from Taxus brevifolia, is a microtubule
      stabilizing agent, which has been shown to block different cells in the G2/M
      phase of the cell cycle and consequently, to modulate their radioresponsiveness.
      Our aim was to test the cytotoxic and radiosensitizing potential of paclitaxel,
      with respect to different gynecological tumors with varying radiosensitivities.
      MATERIAL AND METHOD: We performed clonogenic assays and flow cytometry on 2 cell
      lines, MCF-7 (breast) and CaSki (cervix) cells, and on 2 primary ovarian tumor
      samples (OC-I and OC-II). The cells were irradiated with 200 kV X-rays, radiation
      doses of up to 8 Gy were applied either as single doses or in 2 Gy fractions.
      Paclitaxel concentrations varied from 0.07 to 700 nM, incubation times varied
      from 3 to 120 h. RESULTS: Paclitaxel alone changed the cell cycle distribution of
      the cells tested and was cytotoxic in a time and concentration dependent manner.
      When combined with radiation, most schedules resulted in additive effects of the
      combined treatments. However, for MCF-7 cells, when 7 nM paclitaxel, applied 24 h
      before irradiation, were combined with fractionated irradiation a supra-additive
      effect with a SER of 1.2 was found. For CaSki cells, under comparable conditions
      the SER was 1.13 but the effects were not statistically significant. CONCLUSION:
      Under specific conditions, paclitaxel exerted a weak radiosensitizing effect on
      breast and cervical carcinoma cells. A therapeutic gain may be possible on the
      basis of an optimal paclitaxel/radiation scheduling.

PMID- 9176563
TI  - Increased Na(+)-H+ exchanger activity in the ileal brush-border membrane of
      spontaneously hypertensive rats.
AB  - In the present study, we have examined the intestinal Na+ transport, through the
      Na+)-H+ exchanger in ileal brush-border membrane vesicles (BBMV) isolated from
      spontaneously hypertensive rats (SHR), and normotensive Wistar Kyoto (WKY) rats
      as a control group. Na+ uptake into ileal BBMV was stimulated the presence of a
      proton gradient (pH 5.5 inside/pH 7.5 outside) in SHR and WKY rats, resulting in
      a transient accumulation (overshoot) in both groups of rats. No overshoot was
      observed in the absence of a pH gradient. The magnitude of the accumulation was
      significantly higher in SHR than in WKY rats. Uptake of Na+ at equilibrium was
      identical in the presence and the absence of a proton gradient and was not
      changed in SHR. The use of amiloride inhibited pH gradient-driven Na+ uptake in a
      dose-dependent manner with a Ki of 90 microM and 100 microM for SHR and WKY rats,
      respectively. The relationship between proton gradient-driven Na+ uptake and
      external Na+ concentration was saturable and conformed to Michaelis-Menten
      kinetics in both SHR and WKY rats. Lineweaver-Burk analysis of the pH gradient
      driven Na+ uptake indicated values of Vmax that were significantly increased in
      SHR compared to WKY rats (11.4 +/- 0.55 nmol/mg/8 s vs. 4.96 +/- 0.78 nmol/mg/8 s
      for SHR and WKY rats, respectively). In contrast, similar K(m) for Na+ were found
      between SHR and WKY rats (4.0 +/- 0.2 mM vs. 4.9 +/- 0.6 mM for SHR and WKY rats,
      respectively). These studies show derangement in ileal BBMV Na+ transport of SHR,
      which is characterized by increased Na(+)-H+ exchanger activity.

PMID- 9176562
TI  - Growth inhibition of human pancreatic cancer cells by sphingosylphosphorylcholine
      and influence of culture conditions.
AB  - Sphingosylphosphorylcholine (SPC) has been shown to be a potent mitogen for Swiss
      3T3 fibroblasts and also to be an inhibitor of cell growth of some cancer cells,
      suggesting cell-selective action of the lipid. We examined the effects of SPC,
      and its structurally-related sphingosine (SP), sphingosine 1-phosphate (S1-P) and
      membrane-permeable derivatives of ceramides on cell growth of four strains of
      human pancreatic cancer cells, MLA PaCa-2, PANC-1, PK-1 and PK-9. Under the
      reported conditions for SPC-induced stimulation of 3T3 fibroblasts, where cells
      were grown to confluency in the presence of 10% fetal bovine serum (FBS) in
      culture prior to experiments and insulin was supplemented in experimental
      culture, none of the agents tested stimulated DNA synthesis in MIA PaCa-2 cells
      and ceramide at high concentration even inhibited it. On the other hand, in
      reduced FBS concentration in preculture and in the absence of insulin in
      experimental culture, SP, S1-P and ceramides suppressed cell growth of all the
      cells tested including Swiss 3T3 fibroblasts. However, under these conditions,
      SPC inhibited three out of four species of pancreatic cancer cells but stimulated
      Swiss 3T3 fibroblasts in terms of both DNA synthesis and cell proliferation. Cell
      cycle analysis showed that SPC stimulated cell cycle progress from the G1 to the
      S phase in Swiss 3T3 fibroblasts but inhibited it in PANC-1 cells in reduced FBS
      concentrations. We suggest that extracellular SPC can inhibit cell growth of
      human pancreatic cancer cells through regulation of the cell cycle process
      depending upon both the cell species and environmental conditions.

PMID- 9176564
TI  - A proximo-distal gradient of FGF-like activity in the embryonic chick limb bud.
AB  - In a microassay for anchorage-independent growth in soft agar, NR6 cells form
      colonies in a dose-dependent manner in the presence of fibroblast growth factor
      (FGF). Using this assay system, the ability of thin sequential slices of
      embryonic chick limb bud to promote colony formation was investigated. A
      functional gradient of colony-promoting ability along the proximo-distal axis of
      the developing chick limb bud (stages 22-26) was observed. The highest number of
      colonies was observed in the presence of the most distal slices, and colony
      number decreased progressively at proximal levels. This gradient was specifically
      eliminated by the addition of anti-FGF antibody to the assay, indicating that it
      was caused by a functional gradient of an FGF-like molecule. Limbs of stages 21
      26 were assayed: before this time limb buds are too small to slice in the proximo
      distal axis in the required manner. The FGF-like gradient was observed at stages
      22 to 26.

PMID- 9176565
TI  - Dopamine causes ultrastructural changes in prolactin cells of tilapia
      (Oreochromis niloticus).
AB  - This study was undertaken to examine ultrastructural changes induced by dopamine
      in fish prolactin cells. Tilapia adenohypophyses were incubated with dopamine and
      evaluated by electron microscopy. The quantities of rough endoplasmic reticulum
      (RER) in prolactin cells increased and the number of secretory granules were
      decreased by dopamine (10(-6) mol/l) treatment. Another set of adenohypophysial
      tissues was placed back into control medium for 10 min following a 3 h incubation
      period with dopamine (10(-6) mol/l) (RE10 min group). This group had
      significantly less RER than the 3 h dopamine-treated tissue, and the shape of
      many granules in the RE10 min group changed from spherical to rod-like. In
      addition, some of the granule content appeared to diffuse out of granules since
      some were not fully surrounded by membrane. It was therefore hypothesized that
      the rod-shaped granules might be the result of prolactin secretion by diffusion.

PMID- 9176566
TI  - Effects of amino acid replacements on cadmium binding of metallothionein alpha
      fragment.
AB  - To evaluate whether only 20 cysteine residues at invariant positions are needed
      to bind and coordinate the metals in metallothioneins (MTs), and whether changing
      the positions of cysteine residues in the sequence affects the metal-binding
      capacity and the coordination of MTs, we examined the cadmium-binding affinities
      of seven mutant MT alpha s using an Escherichia coli expression system. Five
      mutant MT alpha s in which the constitutive amino acid residues other than
      cysteines of the alpha-fragment were replaced with glycine residues, and the
      remaining two mutant MT alpha s in which the invariant positions of the cysteine
      residues of the alpha-fragment were shifted, were analysed for their ability to
      be expressed as cadmium-binding forms and for their biochemical properties. The
      results showed that extreme alteration of the constitutive amino acid residues
      other than cysteines in the MT alpha-fragment leads to disruption of their
      cadmium-binding abilities and of their structure. However, mutant MT alpha s
      containing changes of the invariant positions of the cysteine residues were
      expressed in a cadmium-binding form in Escherichia coli, although the invariant
      positions of 20 cysteine residues in the MTs are thought to be important for
      their metal-binding abilities. These results suggest that the position of
      cysteine residues and the chemical nature of the other amino acids in the amino
      acid sequence of MTs are less critical than expected.

PMID- 9176567
TI  - The distribution of alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 4 integrins
      identifies distinct subpopulations of basal keratinocytes in the outer root
      sheath of the human anagen hair follicle.
AB  - The human hair follicle is composed of different concentric compartments, which
      reflect different programmes of differentiation. Using monoclonal antibodies
      against alpha 2 beta 1 and alpha 3 beta 1 integrins we demonstrated a shift in
      their expression, from a basolateral distribution in the basal cells of the lower
      outer root sheath, to an apicolateral expression in the upper outer root sheath,
      as in epidermis. This shift takes place in a transition zone, localized to the
      midpart of the follicle. The distinct basolateral distribution of alpha 2 beta 1
      and alpha 3 beta 1 integrins in the lower portion of the outer root sheath
      coincides with the presence of basal cell protrusions and is probably linked to
      the presence of the vitreous membrane which surrounds the bottom part of the
      anagen human hair follicle. Moreover, we showed that the expression of alpha 6
      beta 4 integrin is discontinuous along the hair follicle and coincides with that
      of laminin 5. Together these results establish that within a given compartment
      namely the outer root sheath-several domains can be clearly identified, which
      probably reflect the onset of successive differentiation pathways along the hair
      follicle.

PMID- 9176568
TI  - PCR amplification and cloning of metallothionein complementary DNAs in temperate
      and Antarctic sea urchin characterized by a large difference in egg
      metallothionein content.
AB  - Metallothionein levels were determined in the eggs of two sea urchin species, the
      Mediterranean Sphaerechinus granularis and the Antarctic Sterechinus neumayeri.
      While appreciable levels of metallothionein were found in S. granularis eggs, a
      negligible amount was detected in S. neumayeri. Two metallothionein isoforms were
      purified from S. granularis, and metallothionein cDNAs were obtained by means of
      reverse transcriptase-polymerase chain reaction (RT-PCR). Two distinct cDNA
      species were cloned and sequenced. The translated amino acid sequences of these
      two forms consisted of 67 residues and differed in two amino acid substitutions.
      Despite the lack of metallothionein in S. neumayeri eggs, a metallothionein cDNA
      was obtained by RT-PCR amplification and a single amino acid sequence coding for
      a 63 residues MT was deduced. A comparative analysis of the primary structure of
      S. granularis and S. neumayeri metallothioneins with those of the other sea
      urchin metallothioneins has been performed. Sea urchin metallothioneins appear to
      be less similar to each other than metallothioneins of closely related
      vertebrates.

PMID- 9176569
TI  - Recombinant and tissue-derived mouse BM-40 bind to several collagen types and
      have increased affinities after proteolytic activation.
AB  - The calcium-binding extracellular matrix protein BM-40 was obtained as a mouse
      cDNA product from a stably transfected kidney cell clone. Electrophoresis and N
      terminal sequence analysis demonstrated absence of the proteolytic processing
      previously observed for a mouse tumour-derived BM-40. Yet the two forms of BM-40
      were very similar in their CD spectra, their calcium-dependent change in alpha
      helix content and their immunological epitopes. In surface plasmon resonance
      assays, recombinant mouse BM-40 showed distinct binding to the triple-helical
      domains of collagens I, II, III, IV and V with Kd = 1-4 microM but no binding to
      collagen VI. These interactions were abolished in the presence of EDTA. Tissue
      derived mouse BM-40, however, bound collagens I and IV with Kd = 0.1-0.2 microM.
      Activation of collagen binding to give a similar Kd could be achieved for
      recombinant mouse BM-40 by treatment with the matrix metalloproteinase
      collagenase-3. The major cleavage site was located in helix C of the
      extracellular calcium-binding module of BM-40 and other less prominent cleavages
      occurred close to the N-terminus. The sensitive helix C site was just one residue
      away from that sensitive to endogenous tissue proteolysis, suggesting that
      cleavage could be a physiological mechanism to modulate collagen binding.

PMID- 9176570
TI  - The increasing burden of disease in Bangladeshi children due to Haemophilus
      influenzae type b meningitis.
AB  - A laboratory-based study of diagnosed bacterial meningitis in the national
      paediatric hospital identified 852 cases of meningitis in the 8-year period 1987
      1994. There were 587 culture-positive cases, of which Haemophilus influenzae
      (47%) and Streptococcus pneumoniae (32%) accounted for 80%. H. influenzae showed
      a remarkable increase of 700% during the study period. Most of the H. influenzae
      cases (90%) occurred in the 1st 2 years of life. Analysis of culture-negative
      specimens by antigen detection in the last 2 years also revealed the predominance
      of H. influenzae (71.4%) and S. pneumoniae (22.4%). Typing of H. influenzae
      isolates during this time showed that 98% of the strains were type b. This
      retrospective hospital-based study indicated a pronounced increase in the
      incidence of H. influenzae meningitis and strongly supports the need for large
      scale Hib vaccination for young children. However, such nationwide intervention
      will probably need to be based on a prospective on a prospective and population
      based surveillance of H. influenzae infections.

PMID- 9176571
TI  - Acute cysticercal meningitis in children: response to praziquantel.
AB  - Acute purulent meningitis as a manifestation of cerebral cysticercosis is
      uncommon. We report two children aged 12 months and 3 years who presented with
      clinical signs of acute meningitis and whose initial cerebrospinal fluid (CSF),
      except for negative culture, was typical of purulent meningitis. However,
      eosinophils were present in subsequent examinations of the CSF and the
      haemagglutination titre for cysticercus rose. Praziquantel was given to both
      children with dramatic improvement in clinical and CSF findings.

PMID- 9176572
TI  - Multi-resistant Staphylococcus haemolyticus in a neonatal unit in New Delhi.
AB  - We describe a cluster of infections in a neonatal nursery due to an infrequently
      reported staphylococcal species, Staphylococcus haemolyticus. S. haemolyticus
      resistant to penicillin, methicillin, gentamicin, erythromycin, chloramphenicol
      and tetracycline (PMGECT) was isolated from a series of infections in neonates
      (conjunctivitis 6, blood 2, pustules 2) over a period of 3 weeks in a neonatal
      nursery. Surveillance cultures from 22 neonates, their mothers in an adjacent
      maternity ward and staff revealed that S. haemolyticus with three resistance
      patterns (PMGECT, PMG and PME) was circulating in the unit. It was isolated from
      two caesarian wounds, the nose/ear/umbilicus of six asymptomatic infants and from
      the noses of three mothers and one nurse. S. haemolyticus showed a higher
      frequency of resistance to antibiotics than Staphylococcus aureus and
      Staphylococcus epidermidis isolated from the unit at the same time. Local and
      asymptomatic infections were treated with local neosporin application whereas
      netilmicin was used to treat systemic infection. Infections were controlled by
      emphasising the importance of handwashing, asepsis and eye care.

PMID- 9176573
TI  - Dexamethasone in laryngeal diphtheritic croup.
AB  - Eighteen children diagnosed as having laryngeal diphtheria with various degrees
      of respiratory obstruction were treated with intravenous dexamethasone in
      addition to penicillin and anti-diphtheritic serum. Reduction in the severity of
      laryngeal obstruction was assessed 12-hourly. Eleven of 12 children with mild-to
      moderate obstruction responded within 24 hours. The 12th child died of toxaemia
      and renal failure following tracheostomy. Four of six with severe obstruction
      also responded within 24 hours. The remaining two underwent tracheostomy, one of
      whom died. Dexamethasone appears to have a role to play in obviating tracheostomy
      in laryngeal diphtheria.

PMID- 9176574
TI  - Prevalence and characteristics of severe rotavirus infections in Nicaraguan
      children.
AB  - We analyzed the prevalence of rotavirus in 296 children age between 3 and 36
      months who were hospitalized in 1994 with severe gastro-enteritis at two health
      centres for diarrhoea treatment in Leon, Nicaragua. Enteric viruses were detected
      in 96 (32.4%) of the children and rotaviruses were the most common pathogens
      detected in 84 (28%). The majority of rotavirus infections occurred in children
      less than 1 year old and all strains isolated belonged to subgroup II and had
      'long' RNA patterns. Molecular epidemiology of 55 rotavirus strains revealed that
      all had the same RNA migration pattern and serotyping of 37 strains by PCR
      technology revealed that all isolates belonged to serotype 3. A significant
      observation was that only one electropherotype of rotavirus circulated. No non
      group A rotaviruses were found by RNA gel electrophoresis. Adenoviruses were
      found by ELISA in 14 of 265 (5%) children and were most frequently detected
      during the 1st year of life. Of 103 faecal samples analyzed by electron
      microscopy, four contained small round structured viruses.

PMID- 9176575
TI  - Kawasaki disease: clustering in infants and pre-school children in Kuwait.
AB  - We report five children who presented within a 2-month period and who all
      fulfilled at least four of the five criteria essential for the diagnosis of
      Kawasaki disease. They were three girls and two boys aged between 5 months and 3
      years. Two of them had atypical presentations; one mimicked infectious
      mononucleosis and the other had severe abdominal pain and was later found to have
      hydrops of the gall bladder. Although treatment was started within the 1st 10
      days of the illness, echocardiographic changes were found in three cases: one had
      myocarditis and the other two showed in the coronary arteries. The occurrence of
      five cases in such as short period of time is similar to the clusterings of
      Kawasaki disease reported in Japan and the USA, and strongly suggests the
      presence of a causative infectious agent.

PMID- 9176576
TI  - Acute lead encephalopathy in early infancy--clinical presentation and outcome.
AB  - We studied 19 infants with a mean age of 3.8 months who presented with features
      consistent with acute lead encephalopathy following the use of traditional
      medicines. All presented with convulsions; CT scans of the brain on admission
      showed brain oedema in four, atrophy in four and normal findings in 11.
      Cerebrospinal fluid analysis in nine patients showed pleocytosis in six and a
      high protein content in eight. The median lead level in these 19 infants which
      encephalopathy was 3.6 mumol/l (74.5 micrograms/dl). Seven had a mean lead level
      of only 2.7 mumol/l (56.9 micrograms/dl) which is much below 70 micrograms/dl,
      the level usually proposed as the threshold for encephalopathy. Thirteen infants
      developed brain damage during follow-up; statistical analysis correlated the lead
      level at 2 months post chelation with an abnormal neurological outcome. Our
      findings indicate that in very young infants acute lead encephalopathy may occur
      at lead level lower than previously reported.

PMID- 9176577
TI  - Chloroquine-induced vitiligo-like depigmentation.
AB  - A 6-year-old girl of Ethiopian origin with atopic eczema from the age of 2 years
      is reported. Prior to a visit to her grandparents in Ethiopia, she received 250
      mg chloroquine weekly as prophylaxis against malaria. Three weeks later she
      developed sharply demarcated depigmentation on the face, especially in the
      peritoneal area. On returning home to Norway, the medication was discontinued and
      after a few weeks the first repigmentation was noticed. Complete repigmentation
      was observed 1 year after cessation of chloroquine therapy.

PMID- 9176578
TI  - The epidemiology and clinical features of paraffin (kerosene) poisoning in rural
      African children.
AB  - One hundred and eleven children under 5 years of age admitted with a diagnosis of
      paraffin ingestion, constituting 9.1% of total ward admissions in this age group,
      were studied prospectively. The majority were between 13 and 36 months old. One
      fifth of the children were in the care of another child at the same time of
      ingestion. Fourteen families had a past history of paraffin ingestion. Only 22%
      of households normally stored in paraffin above ground level and in only 15% of
      cases was paraffin stored in a container specified for that purpose. Emesis was
      attempted using home remedies in 72% of cases and was associated with a
      significant increase in vomiting. Vomiting had an impact on the exacerbation of
      the clinical features of paraffin poisoning, particularly fever. Clinical
      criteria laid down for suspected superadded bacterial lung infection resulted in
      half of the study group having blood cultures performed on day 1 and another 17
      on day 4. Only two yielded isolates which possibly could have been indicative of
      bacteremia secondary to infective pneumonia. No child in the suspected group was
      treated with antibiotics and all recovered uneventfully. Admission chest X-rays
      contributed little to the management of the illness. Paraffin ingestion remains a
      serious contributor to child morbidity in rural South Africa and there appears to
      be room for further preventive education at community level. Specific measures
      could include storage of paraffin in designated containers above ground level and
      emphasis on adult supervision of children. Superadded bacterial pneumonia is
      uncommon and antibiotics in the management of suspected cases are not routinely
      indicated.

PMID- 9176579
TI  - Acute mercury vapour poisoning in an infant.
AB  - Mercury vapour inhalation is a rare cause of acute toxic injury to the lungs and
      is often fatal in infants. A 5 month-old girl with mercury vapour poisoning who
      developed chemical pneumonitis with bilateral pneumothoraces is reported. She was
      managed successfully in an intensive care unit with respiratory support, without
      chelation therapy.

PMID- 9176581
TI  - Total and percentage body water in healthy Nigerian children aged 5-15 years.
AB  - Bioelectrical impedance was used to measure total body water in Nigerian children
      in a clinical setting. Total body water and percentage body water were determined
      in 454 boys and 450 girls, all healthy Nigerian children aged between 5 and 15
      years. The age range and total body water were similar in both sexes but
      percentage body water was significantly higher in boys than in girls (p =
      0.000001). Total body water increased with age in both boys and girls. Percentage
      body water increased with age but not significantly so in boys (p > 0.076) and
      decreased significantly with age in the girls (p = 0.008), an indication of
      differences between the sexes in how the proportion of body fat mass changed with
      age. These data are very similar to those reported in the literature. The
      bioelectrical impedance method for body water determination is non-invasive,
      cheap, portable and well accepted by children. Its more general clinical
      application in paediatric practice is recommended.

PMID- 9176580
TI  - Tuberculosis and myelofibrosis in children: a report.
AB  - Seven children, six boys and a girl, aged from 2 to 15 years with proven
      myelofibrosis are reported. The clinical presentation in each of them was more or
      less similar with weight loss, moderate or low-grade fever, and abdominal
      distension with pain or discomfort for some months. They had hepatosplenomegaly.
      The spleens, enlarged to more than 6 cm below the costal margin, were smooth,
      firm and not tender. There was a variable degree of generalized lymphadenopathy.
      They were diagnosed as myelofibrosis associated with tuberculosis. The clinical
      response to anti-tuberculous chemotherapy was remarkable. Extensive search should
      be made for evidence of tuberculosis in children presenting with myelofibrosis.

PMID- 9176582
TI  - Cor pulmonale: an unusual presentation of tropical eosinophilia.
AB  - Tropical pulmonary eosinophilia (TPE) is considered to be a variant of human
      filarial infection. The pulmonary manifestations of TPE have been well described.
      Extra-pulmonary features of the disease, although not commonly seen, have been
      reported previously. A 9-year-old Malay girl with a history of recurrent cough
      and wheezing was admitted because of cardiac failure. Physical examination
      revealed a very sick girl with tachypnoea, central cyanosis, finger clubbing,
      elevated jugular venous pulse, generalized crackles and rhonchi in the chest, a
      loud second heart sound and hepatosplenomegaly. A chest radiograph showed
      cardiomegaly and right pleural effusion. Laboratory investigations revealed
      hypochromic, microcytic anaemia with persistent blood eosinophilia (absolute
      eosinophil counts varied from 1.9 to 5.5 x 10(9)/1). The ELISA test for
      antifilarial IgG antibodies was strongly positive. She responded promptly to
      treatment with diethylcarbamazine. In summary, this is a patient with TPE who
      presented with cor pulmonale, probably due to late-stage interstitial pulmonary
      fibrosis. In order to prevent the long term morbidity of cardiorespiratory
      disability, the early signs of TPE should be recognized and the infection
      treated.

PMID- 9176583
TI  - Age-related pattern of immunoglobulins G, A and M in children born to HIV
      seropositive women.
AB  - In a cohort of 56 children born to HIV-seropositive African women, 19 met the
      criteria for HIV-infected children and 37 remained antibody-negative at 18 months
      of age. Blood samples taken at birth and 3-monthly until 18 months of age were
      processed and analysed by laser nephelometry for serum immunoglobulin (IgG, IgA
      and IgM) levels. In the infected group of children. higher levels of IgG were
      observed during their 1st 18 months of life reaching statistical significance at
      3, 6, 15 and 18 months. Higher levels of IgA at 3 months and at 15 and 18 months,
      and higher levels of IgM at 3 months and 18 months later were statistically
      significant. All four infected children who died before the age of 6 months
      showed signs of hypergammaglobulinaemia (IgG and IgA) by 3 months of age. In this
      study the earliest and most common immunological abnormality was
      hypergammaglobulinaemia and infected infants with higher morbidity and mortality
      had more evident immunoglobulin abnormalities than infected children who
      survived. However, the immunological abnormalities in this small cohort did not
      precede the onset of severe symptoms and cannot therefore be used to predict
      clinical outcome.

PMID- 9176584
TI  - Body temperature is a poor predictor of malaria parasitaemia in children with
      acute diarrhoea.
AB  - In order to ascertain the usefulness of a temperature > or = 38 degrees C or a
      history of fever in detecting malaria parasitaemia in children with diarrhoea as
      recommended by the World Health Organization (WHO), 522 children aged from 6 to
      60 months presenting with acute diarrhoea were studied in Ibadan, Nigeria. The
      overall prevalence of malaria parasitaemia was 13%. There was no significant
      difference in the prevalence of parasitaemia between patients with a temperature
      > or = 38 degrees C and those < 38 degrees C. Neither was any difference found in
      the prevalence of parasitaemia between those with and those without a history of
      fever. Temperature > or = 38 degrees C had a low sensitivity (53%) and
      specificity (57%) and a low positive predictive value (16%) in detecting malaria
      parasitaemia. A history of fever had a higher sensitivity (79%) than temperature
      > or = 38 degrees C in detecting malaria parasitaemia but a low specificity (27%)
      and low positive predictive value (14%). Similar results were obtained in a
      simultaneously studied non-diarrhoea control group of 313 children. The
      implications of using the current WHO guidelines is that many diarrhoea patients
      with malaria would not be identified, while many patients without malaria would
      be treated unnecessarily. The latter situation may be associated with the
      development of drug-resistant malaria parasites while the children are
      unnecessarily exposed to the risk of drug-related complications. It is
      recommended that while the search for better guidelines continues children should
      be screened for malaria parasitaemia before treatment, where facilities are
      available.

PMID- 9176585
TI  - Childhood brain abscess in Saudi Arabia.
AB  - The characteristics of childhood brain abscess in Saudi Arabia are outlined in
      this review of 17 consecutive cases treated at King Khalid University Hospital
      (KKUH) between 1985 and 1994. The data on 20 consecutive adults with brain
      abscess treated at KKUH during the same period were also analysed. Compared with
      series from the West, the children were unusual because of the relatively low
      incidence of cardiogenic and anaerobic abscesses and the relatively high
      incidence of post-traumatic, infratentorial and staphylococcal abscesses and
      sterile cultures. Compared with cases of brain abscess in adults, the children
      showed a much lower incidence of idiopathic abscess, a higher incidence of
      infratentorial abscess and a much better outcome. Factors accounting for the zero
      mortality rate in these children are discussed.

PMID- 9176586
TI  - Renal agenesis and ureteropelvic junction obstruction in an infant with Turner
      syndrome.
AB  - An infant who had Turner syndrome with left renal agenesis and right
      hydronephrosis due to functional ureteropelvic junction obstruction is reported.
      The importance of routine imaging for early identification of potentially serious
      renal anomalies in patients being evaluated for short stature and possible Turner
      syndrome is emphasized.

PMID- 9176587
TI  - Wall shear rate measurements in an elastic curved artery model.
AB  - Since atherosclerotic lesions tend to be localized at bends and branching points,
      knowledge of wall shear rate patterns in models of these geometries may help
      elucidate the mechanism of atherogenesis. This study uses the photochromic method
      of flow visualization to determine both the mean and amplitude of the wall shear
      rate wavefront in straight and curved elastic arterial models to demonstrate the
      effects of curvature, elasticity, and the phase angle between the flow and
      pressure waveforms (impedance phase angle). Under sinusoidal flow conditions
      characteristic of large arteries, the mean shear rate at the inner wall of the
      curved tube is reduced 40-56% from its steady flow value, depending on the phase
      angle. Wall shear rate amplitudes in the curved tube are significantly reduced by
      wall motion (36-55% of the Womersley amplitude for a straight rigid tube). The
      shear rate amplitude at the outer wall decreases 30% as the phase angle is
      reduced from -20 degrees to -66 degrees, while the shear rate amplitude at the
      inner wall increases 45%. As a result, the oscillatory nature of flow at the
      outer wall decreases with decreasing negative phase angle, but flow at the inner
      wall becomes much more oscillatory. At large negative phase angles,
      characteristic of hypertension or vasoactive agents, the shear rate at the inner
      wall has a small mean and cycles through positive and negative values; the shear
      rate at the outer wall remains positive throughout the flow cycle. Thus, the
      impedance phase angle could affect atherogenesis along the inner wall if temporal
      and directional changes in wall shear rate play a role.

PMID- 9176588
TI  - The superposition of steady on oscillatory shear and its effect on the
      viscoelasticity of human blood and a blood-like model fluid.
AB  - To understand the pulsatility of human blood flow in vivo, it is necessary to
      separately investigate (1) steady shear and oscillatory flow, and (2) the
      superposition of steady shear flow on oscillatory flow performed under in vitro
      conditions. In this study a variable steady shear rate was superimposed in
      parallel on oscillatory shear at a constant frequency (0.5 Hz) for human blood
      (45% hematocrit), and an aqueous polyacrylamide polymer solution (AP 30E,
      concentration 300 ppm). The effect of superposition of the above two shear flows
      on the viscoelasticity of blood was more pronounced for the elastic (eta") than
      for the viscous (eta') component of viscoelasticity. With increasing superimposed
      shear rate, both eta' and eta" decreased, especially at the low shear region.
      This behavior can be explained by the viscoelastic properties of blood and the
      phenomenon of blood aggregation and disaggregation. Quantitatively, the
      dependence of the viscous component of complex viscosity on superimposed shear
      for both blood and polymer solution is described by a modified Carreau equation.
      The elastic component of complex viscosity decreased exponentially with
      increasing superimposed shear, and it is described by an exponential model.

PMID- 9176589
TI  - Model studies of leukocyte-endothelium-blood interactions. II. Hemodynamic impact
      of leukocytes adherent to the wall of post-capillary vessels.
AB  - Computational fluid dynamics (CFD) and large scale model experiments were used to
      analyze the hemodynamic impact of leukocytes adherent to the wall of post
      capillary venules. Using a large scale model and, with the aid of a finite
      element package, solving the Navier Stokes equations for low Reynolds number flow
      in a cylinder past an adherent sphere, we have developed a dimensionless
      correlation which permits the estimation of the pressure drop across an adherent
      leukocyte in an in vivo vessel. This relationship is: f.Re = exp[2.877+4.630
      (d/D)4] where f is the Fanning friction factor, Re is the Reynolds number and d/D
      is the leukocyte to vessel diameter ratio. The friction factor is proportional to
      the pressure drop across the leukocyte, and does not significantly increase until
      d/D is greater than 0.5, and then increases rapidly with increasing d/D.
      Computations indicate that the length of the disturbed flow region generated by
      an adherent leukocyte increases with decreasing vessel size. The average wall
      stress in the disturbed flow region remains constant, and equal to the wall
      stress in the undisturbed region for d/D less than approximately 0.5. For d/D
      greater than 0.5, the average wall stress in the disturbed flow region increases
      rapidly with increasing d/D. There is an even larger increase, up to five times
      greater than the average disturbed stress, in the peak wall stress in the
      disturbed flow region. This indicates that significant wall stress gradients can
      be generated by an adherent leukocyte in post-capillary size vessels.

PMID- 9176590
TI  - Shear stress-induced binding of von Willebrand factor to platelets.
AB  - Shear stress-induced platelet aggregation requires von Willebrand factor (vWF),
      platelet glycoprotein (GP) Ib, GPIIb-IIIa, Ca2+, and adenosine diphosphate (ADP).
      Recent reports using vWF labeled with either 125I or fluorescein isothiocyanate
      (FITC) have demonstrated that in shear-fields, vWF binds to both GPIb and GPIIb
      IIIa. The sequence of the vWF finding to the two platelet receptors has not been
      precisely determined in these reports. In this study, a flow cytometry technique
      using a primary anti-vWF antibody and a secondary FITC IgG antibody was used to
      measure shear stress-induced vWF binding to platelets. Washed normal platelets
      suspended at 50,000/microliters with purified large vWF multimers were exposed to
      laminar shear stresses of 15 to 120 dynes/cm2 for 30 sec. At this low platelet
      count, little or no aggregation occurred in the shear fields. A significant
      increase in post-shear vWF-positive platelets was consistently observed.
      Experiments with platelets from normal and severe von Willebrand's disease (vWD)
      (which lack plasma and platelet alpha-granule vWF) demonstrated that exogenous
      vWF predominately contributed to the platelet-vWF binding. Blockade of platelet
      GPIb with the monoclonal anti-GPIb antibody, 6D1, completely inhibited shear
      stress-induced platelet-vWF attachment. In contrast, blockade of GPIIb-IIIa with
      monoclonal anti-GPIIb-IIIa antibodies, 10E5, or c7E3, or with the GPIIb-IIIa
      blocking tetrapeptide, RGDS had little or no inhibitory effect on platelet-vWF
      binding. These data demonstrate that the binding of vWF to GPIb is likely to be
      the initial shear-induced platelet-ligand binding event.

PMID- 9176591
TI  - Flash freezing of erythrocyte suspensions.
AB  - Freezing whole blood in bulk usually results in severe cellular destruction
      through the action of ice crystals and osmotic effects in the freezing liquid.
      The potential of flash freezing blood aerosols onto a liquid nitrogen surface as
      a means of inhibiting cellular damage was studied in this work. Three commercial
      spraying devices were employed to spray-freeze either whole blood or concentrated
      erythrocyte suspensions, using hydroxyethyl starch (HES) as a cryoprotectant. The
      integrity and viability of the processed cells were assessed by measuring gross
      rheological properties and the extent of hemolysis. Cells were found to be
      susceptible to the very high shear stresses imposed by some of the spraying
      devices. Bulk freezing of blood, even in the presence of cryoprotectant, resulted
      in complete cellular destruction. Whereas flash freezing was capable of
      substantially reducing the level of hemolysis to 12.6% and preserving the
      cellular deformability.

PMID- 9176592
TI  - The role of specialist advisory committees in the new training schemes.

PMID- 9176593
TI  - Who owns AIDS?

PMID- 9176594
TI  - Haemofiltration: how to do it.
AB  - Haemofiltration and its variants are simple procedures which allow the management
      of patients with renal failure in intensive therapy units without the need for
      continual support from renal specialists. In order for non-renal specialists to
      manage the practical aspects of these treatments logically, safely and
      successfully it is important to understand the basic principles involved.

PMID- 9176595
TI  - Nuclear cardiology.
AB  - Nuclear cardiology techniques allow non-invasive assessment of myocardial
      perfusion and ventricular function. They have a major role in the diagnosis of
      coronary artery disease, in risk stratification of patients with the disease, in
      the determination of myocardial viability, and in the evaluation of the
      functional impact of known coronary artery lesions.

PMID- 9176596
TI  - Mivacurium.
AB  - The muscle relaxant mivacurium was introduced in 1988 as a non-depolarizing drug
      with the pharmacokinetic profile of suxamethonium. Like suxamethonium, mivacurium
      is hydrolyzed by plasma cholinesterase; however, it has proved to be slower in
      onset and considerably longer in its duration of action. Inspite of this, in
      clinically used doses, it is somewhat shorter acting than alternative non
      depolarizing drugs.

PMID- 9176597
TI  - In the public's view...screening but not seeing.

PMID- 9176598
TI  - Headaches in the accident and emergency department.
AB  - Serious illness is not uncommon in patients attending accident and emergency
      departments with headache. Careful clinical assessment, focusing on
      characteristics of the headache, associated symptoms and certain examination
      findings, helps to identify those at risk, and permits the efficient management
      of everybody else.

PMID- 9176599
TI  - Hysterectomy and bone mineral density.

PMID- 9176600
TI  - Longitudinal assessment of bone density with hormone replacement therapy.

PMID- 9176601
TI  - Bone preservation and the menopause.

PMID- 9176602
TI  - The effects of chemotherapy on the long-term survivors of malignancy.
AB  - It is estimated that by the year 2000 one in a thousand 20-year-olds will be a
      survivor of childhood cancer. Increasingly, chemotherapy alone is being used
      because of concerns about the long-term effects of radiotherapy. However,
      chemotherapy may also have long-term effects particularly on growth and body
      composition, cardiac function and fertility. Other important late effects include
      renal and lung toxicity, hearing impairment, neuro-psychological sequalae and
      secondary leukaemias.

PMID- 9176603
TI  - Perioperative cardiovascular optimization: importance and relevance for
      anaesthesia.

PMID- 9176604
TI  - A district stroke service.
AB  - Stroke is the third most common cause of death in Britain, but despite its
      medical and economic importance, management of the three facets of stroke-
      prevention, acute care and rehabilitation--has been unstructured and poor value
      for money. This article considers how these issues might be more effectively
      addressed by a pragmatic coordinated approach to the whole problem of stroke in a
      health authority.

PMID- 9176605
TI  - Who owns AIDS?

PMID- 9176606
TI  - Recombinant proteins.

PMID- 9176607
TI  - Value for money in the NHS.
AB  - Value for money is becoming increasing important in the current NHS climate. The
      Audit Commission, a statutory body appointed to provide an external audit service
      for the NHS in England and Wales, aims to work with audited bodies to identify
      economy, efficiency and effectiveness in the services offered by the NHS to help
      improve patient care.

PMID- 9176608
TI  - The financial year-end health check.

PMID- 9176610
TI  - Diagnosis and treatment of parotid tumours.
AB  - Diagnosis and treatment of 51 cases of parotid tumour seen and treated in King
      Fahad National Guard Hospital, Riyadh, are discussed here. More emphasis is
      placed on proper clinical history and physical examination of patients with
      parotid lump because usually this will provide enough information to the
      clinician about the nature of the swelling. Imaging studies are helpful in
      supporting the clinical diagnosis and determining the extent of the lesion
      particularly in cases of malignant tumours. Fine needle aspiration biopsy needs
      an expert cytologist for salivary gland neoplasm and the need for proper
      communication between the surgeon and cytologist is stressed. All 51 cases
      underwent surgical excision which is the treatment of choice. Follow-up periods
      were variable and short.

PMID- 9176609
TI  - Extended applications of endoscopic sinus surgery--the territorial imperative.

PMID- 9176611
TI  - Correlation between retractions of the pars flaccida and the pars tensa.
AB  - Retractions of the pars flaccida (PF) and the pars tensa (PT) were assessed in
      250 atelectatic ears in an attempt to find out the way in which the differences
      in mechanical properties of the two parts of the tympanic membrane are reflected
      clinically. Retraction of PF was found in 217 ears (86.8 per cent) and retraction
      of PF in 150 (60 per cent). The concomitant presence of both types of retraction
      was observed in 117 ears (46.8 per cent) while 133 (53.2 per cent) had only one
      type, 100 of them (75.1 per cent) PF retraction and 33 (24.9 per cent) PT
      retraction. When only one type of retraction was present, the empirical
      probability of having a PF retraction was 75.1 per cent, while the probability of
      having a PT retraction was only 24.9 per cent. Clinically, the more frequent
      occurrence of PF retraction in the absence of PT retraction than vice versa
      reflects the greater collapsibility of the PF. When both types of retractions
      were present, we found a positive correlation between their severity.

PMID- 9176612
TI  - Cochlear implantation in a district general hospital: problems and complications
      in the first five years.
AB  - Fifty-three patients, 34 adults and 19 children have been implanted over the
      first five years of the cochlear implant programmed at the North Riding Infirmary
      (NRI). For a small centre, based at a district general hospital, our complication
      rate compare favourably with others: 11.7 per cent adult and 10.5 per cent
      paediatric major complications. Data on all patients was gathered prospectively
      as part of the national cochlear implant programme, and we report and discuss all
      complications from this centre.

PMID- 9176613
TI  - Anatomical considerations of high jugular bulb in lateral skull base surgery.
AB  - In order to study high jugular bulb management in lateral skull base surgery, an
      anatomical study was conducted on 30 temporal bones by examining the relationship
      between the internal auditory canal (IAC) and the jugular bulb. The following
      parameters were measured: 1) Height of the jugular bulb (H)... distance between
      the level of jugular bulb dome and the line passing through the confluence of the
      sigmoid sinus with the jugular bulb (SS-JB), 2) Mastoid length (ML)... distance
      between the mastoid process and middle cranial fossa dura, 3) Distance between
      the most inferior part of the porus acousticus and jugular bulb dome (A), 4)
      Distance between the porus acousticus and SS-JB (B). The jugular bulb was defined
      as high when it occupied more than two thirds of (B). The incidence of a high
      jugular bulb was 23 per cent in this study. When the jugular bulb was high, the
      mean (H) and (A) were 9.4 +/- 1.9 mm and 2.7 +/- 0.5 mm, respectively. (H) was
      higher on the right side than on the left side. No statistically significant
      difference was found between small and large mastoids (t-test: p > 0.05). It was
      concluded that when a high jugular bulb was encountered during lateral skull base
      surgery, the jugular bulb position allows a very small working area inferior to
      the IAC. In these cases, a 3 or 4 mm depression of the jugular bulb is necessary
      in order to expose the lower cranial nerves. This can be accomplished by lowering
      the jugular bulb with the technique already described.

PMID- 9176614
TI  - Nasal mucosal congestion during the menstrual cycle.
AB  - A relationship between the reactivity of the nasal mucosa and changes in female
      sex hormones have been debated for a long time, although no evidence has been
      presented to prove or disprove this relationship. Nasal patency was therefore
      measured by nasal expiratory peak-flow in 26 women for two months in order to
      study changes in nasal mucosal congestion during the menstrual cycle. In another
      eight women, nasal congestion was measured by acoustic rhinometry, and symptoms
      of nasal stuffiness were registered during periods when there were various levels
      of plasma oestradiol and progesterone. Finally, nasal mucosal biopsies were taken
      for preparation of receptors for oestradiol and progesterone. This study could
      not verify the effects of female sex hormones on the nasal mucosa. This could be
      explained by the fact that no receptors for oestradiol and progesterone were
      found.

PMID- 9176615
TI  - Mast cell ultrastructure in the inferior turbinate and stroma of nasal polyps.
AB  - Fourteen unselected adult patients with nasal polyps had ultrastructural
      examination of mast cells from matching biopsies of the polyp and inferior
      turbinate. Between three and 10 blocks were examined for each patient in both
      tissues and every mast cell that had a nucleus was photographed for study. Fifty
      three mast cells were found within the stroma of nasal polyps and 54 in the
      submucosa of the inferior turbinate biopsies. The number of granules ranged
      between 13 and 167 (mean 60) for polyps and 18 and 148 (mean 61) in the inferior
      turbinate. The mast cells appeared essentially normal in the inferior turbinate
      of four patients. The degree of degranulation of the mast cells was calculated as
      in previous studies and then averaged for both the polyp and the inferior
      turbinate of each patient. There was greater degranulation in the nasal polyp
      compared to inferior turbinate (p = 0.03). These results were compared with mast
      cell degranulation found in the normal nose and in the inferior turbinate of
      patients with perennial allergic rhinitis which we previously published. The
      inferior turbinates in these patients were more degranulated than the normal nose
      (p = 0.0001) but were similar to that found in patients with perennial allergic
      rhinitis. This suggested that some degree of degranulation may occur throughout
      the nose in two thirds of the patients with nasal polyps which supports the
      theory that mast cell reactions are not limited to the polyps in a proportion of
      patients.

PMID- 9176616
TI  - Snoring and oral submucous fibrosis.
AB  - Forty patients above the age of 40 years with oral submucous fibrosis were
      studied to determine the frequency and severity of snoring. The results were
      compared with a controlled group of similar sex and age for presence of snoring.
      The present study indicates that patients with oral submucous fibrosis having a
      short and fixed uvula and scarred soft palate are less likely to develop snoring.
      Thus it is suggested that in laser surgery or in classical uvulopalatopharyngeal
      surgery, the uvula and soft palate should be reduced in size and volume to the
      extent of that found in oral submucous fibrosis.

PMID- 9176617
TI  - Neonatal and paediatric fibre-optic laryngoscopy and bronchoscopy using the
      laryngeal mask airway.
AB  - Endoscopy of the upper airways in neonates and infants was traditionally been
      accomplished using rigid laryngoscopes and bronchoscopes. The laryngeal mask may
      be used both to control the airway for anaesthetic ventilation and to guide a
      fibre-optic endoscope to the laryngeal inlet and beyond. We report our experience
      with five neonatal and paediatric cases where fibre-optic laryngoscopy and
      bronchoscopy were performed through the laryngeal mask airway. All were cases in
      which standard rigid endoscopy had proved difficult with only a poor and
      restricted view of the laryngeal inlet being obtained due to the age of the
      infants, or abnormal anatomy of the upper airways. No problems have been
      encountered with maintenance of the airway or with endoscopic view obtained. In
      fact in neonatal patients, this technique has been found to be preferable with
      regard to safety and ease of use when compared to the ventilating bronchoscope.
      With the size 1 laryngeal mask airway it is not possible to simultaneously
      ventilate and endoscope the patient. Cases included, a vascular ring, Goldenhar's
      syndrome, laryngomalacia, supraglottis and vocal fold paresis. This technique
      provides a secure method of maintaining anaesthetic ventilation during airway
      endoscopy, and also a means of easily locating the glottis.

PMID- 9176618
TI  - Cricothyroidotomy and the anatomy of the cricothyroid space. An autopsy study.
AB  - Airway management is one of the main dictums in anaesthesia, emergency medicine
      and critical care. Endotracheal intubation, tracheostomy and cricothyroidotomy
      are all approved methods to secure a patient's airway. Cricothyroidotomy is
      performed in the space between the anterior inferior border of the thyroid
      cartilage and the anterior superior border of the cricoid cartilage. We studied
      107 autopsies with special interest in the anatomy of the cricothyroid space.

PMID- 9176619
TI  - Pre- admission clinics in ENT: a national audit of UK practice and opinion.
AB  - A one-year prospective audit (1989) of patient non-attendance for elective
      surgery in our department showed that of those summoned, five per cent defaulted
      on the day of admission without contacting the hospital (Hampal and Flood, 1992).
      Contributing factors such as lengthy waiting lists and inefficient communication
      with the patients were amenable to correction by the hospital. However, the
      current admission policy made inevitable a significant waste of theatre time. The
      pre-admission clinic (PAC), an outpatient attendance shortly before surgery, was
      recommended in ENT practice by Robin (1991) and introduced into our department
      the year. Failure to attend the PAC allowed adequate time for replacement on the
      theatre list and was recommended as a solution to the problem of unfilled theatre
      sessions (Dingle et al., 1993). A subsequent four-year experience of conducting
      PACs has confirmed several expected advantages. However, some of the hopes for
      development expressed in our earlier work (Dingle et al., 1993) have failed to
      materialize. This study aims to review retrospectively our experience and compare
      it with the admission practice and desires of ENT departments in the United
      Kingdom as revealed by a postal survey. The findings are of relevance to all
      surgical specialties and to anaesthetic departments wishing to adopt this system
      of admission.

PMID- 9176620
TI  - A valuable device in the management of epistaxis.
AB  - A suction end for use in epistaxis is presented. It has advantages over commonly
      used devices in offering a comfortable length for handling and adequate diameter
      for effective control of severe haemorrhage. It is also disposable which reduces
      the risk of blood borne transmission of diseases.

PMID- 9176621
TI  - A homemade modification of a spacer device for delivery of bronchodilator or
      steroid therapy in patients with tracheostomies.
AB  - Patients who have artificial airways and who concurrently suffer with chronic
      obstructive airways disease encounter problems when administering inhaled
      bronchodilator and corticosteroid drugs via the tracheostomy. This is because
      most the devices are designed to deliver the metered dose of inhaled drugs via
      the oropharyngeal route and it is impossible to obtain an airtight seal from the
      inhaler device mouthpiece to the tracheostomy tube. The author describes a
      simple, effective and cheap modification of a spacer device designed by a
      creative patient to facilitate delivery of the aerosol via the tracheostomy tube
      to overcome this problem.

PMID- 9176622
TI  - Occupational otitis externa in chicken catchers.
AB  - Otitis externa is only occasionally occupational in origin and infestations of
      the ear are even less common. Two cases of occupational otitis externa due to
      infestation with Dermanyssus gallinae, the red poultry mite, are reported
      occurring in poultry workers.

PMID- 9176623
TI  - Chondrosarcoma of the petrous apex. Dilemmas in diagnosis and treatment.
AB  - A case of chrondrosarcoma of the petrous temporal bone is presented.
      Chondrosarcomas rarely occur intracranially and typically present apex mass. The
      dilemmas faced in the diagnosis and treatment of petrous apex chondrosarcomas are
      discussed. This case also gives interesting insight into the natural history of
      this tumour.

PMID- 9176624
TI  - Fronto-ethmoid osteoma: the place of surgery.
AB  - Osteomas of the paranasal sinuses are common. Most are, however, asymptomatic and
      a chance radiographic finding. We describe four cases histories which help to
      illustrate the benefits and hazards of surgery, and highlight the importance of
      patient selection. A review of the literature is presented.

PMID- 9176625
TI  - Malignant melanoma arising in the frontal sinuses.
AB  - Sinonasal malignant melanoma is rare and usually occurs in the nasal cavity.
      Presentation is often varied and occurs late in the natural history of the
      disease, resulting in a poor prognosis. A case is reported of a patient with
      malignant melanoma arising from the frontal sinus who presented with a forehead
      swelling and progressive confusion. A review of the literature on malignant
      melanoma in the nasal cavity and paranasal sinuses regarding its presentation,
      site of origin and principles of management is discussed.

PMID- 9176626
TI  - Tonsillar metastasis from a renal cell carcinoma presenting as a quinsy.
AB  - We present a rare case of renal cell carcinoma metastatic to the tonsil.
      Tonsillectomy was inadvertently performed during an attempt to drain what was
      clinically a peritonsillar abscess.

PMID- 9176627
TI  - Treatment of recurrent respiratory papillomatosis with argon plasma coagulation.
AB  - Extension of recurrent respiratory papillomatosis (RRP) to the lower airway in
      children is life-threatening and an extremely difficult condition to treat. We
      present the case of a seven-year-old girl with progressive RRP since the age of
      two. Repeated CO2 laser treatment and interferon-alpha treatment could not
      prevent tracheotomy and spread to the trachea. We used argon plasma coagulation
      (APC) with flexible endoscopy for the first time for the treatment of RRP. APC
      gives a controlled limited penetration into the tissue and good control of
      bleeding. There is no carbonization or vaporization which makes it a suitable
      method for the treatment of lower airway RRP. After a few treatments with APC, we
      gained very good control of the disease with no side-effects or complications.
      The described application of APC seems to be a promising way to treat lower
      airway RRP.

PMID- 9176628
TI  - Thoraco-cervical fibromatosis: treatment of surgical excision.
AB  - We present a case of massive thoraco-cervical fibromatosis treated by sternotomy
      and simple excision. The patient remains disease-free after careful follow-up of
      three years. We suggest that if the lesion is encapsulated and position or size
      prevents en bloc removal, simple excision may be curative.

PMID- 9176629
TI  - Pneumopericardium: an unusual manifestation of blunt tracheal trauma.
AB  - A case of pneumopericardium in a child following blunt injury to his trachea is
      described. Such a case has not been previously described in the literature. A
      probable anatomical explanation for this rare event is offered.

PMID- 9176630
TI  - Computerized tomographic and ultrasonographic features of Kimura's disease.
AB  - Kimura's disease (KD) is an uncommon condition once thought to affect only
      Orientals. The patients present with swelling of the major salivary glands
      associated with cervical lymphadenopathy. The clinical, histopathological and
      radiological findings of a young Caucasian female with KD will be presented and
      discussed.

PMID- 9176631
TI  - Direct microscopy of effusions obtained from peritonsillar abscesses as a
      complement to bacterial culturing.
AB  - Effusion material was aspirated from 51 consecutive peritonsillar abscesses (34
      male, 17 female; age range eight to 46 years) and subjected to direct microscopy
      after staining with acridine orange. Bacteria were counted per ml effusion
      material and their morphology was analyzed. In addition, aerobic and anaerobic
      bacterial culturing was performed. Effusions containing beta-haemolytic
      streptococci Group A, which appeared as a single species contained fewer bacteria
      (8 x 10(6) per ml, median value) than effusions harbouring a mixed flora (7 x
      10(8) bacteria per ml, median value). Direct microscopy of effusions obtained
      from peritonsillar abscesses makes possible rapid identification of a single or
      mixed flora, which is of importance for the antibiotic treatment of the disease.

PMID- 9176632
TI  - Tuberculosis of the ear and a Nepalese experience.

PMID- 9176633
TI  - Stochastic events underlie Ca2+ signalling in neutrophils.
AB  - In order to probe the events which couple receptor occupancy to elevation of
      cytosolic free Ca2+ fast laser scanning of fluo3-loaded neutrophils was used to
      determine the timing of the initial phase of the Ca2+ response. This approach
      demonstrated that there was a measurable delay between the addition of stimulus
      and the onset of the cytosolic free Ca2+ signal which varied from cell to cell
      variable from 75 ms to greater than 1.5 s. The distribution of lag times was
      similar to that expected if the delay resulted from a series of obligatory
      stochastic processes. From the Poisson equation, a probability density function
      for the delays was generated which depended on n, the number of stochastic events
      in the series, and lambda, the stochastic rate for the events. The best fit
      between the data and theory was found to be for six stochastic steps in the
      series occurring with a stochastic rate similar to that expected for diffusion of
      known small molecular weight signalling molecules within the cell. We, therefore,
      propose that the delays in onset of the Ca2+ response in neutrophils were the
      result of sequence of diffusion steps, each with sufficiently small numbers of
      intracellular messenger molecules to generate stochastic behaviour.

PMID- 9176634
TI  - Cross-species protein identification using amino acid composition, peptide mass
      fingerprinting, isoelectric point and molecular mass: a theoretical evaluation.
AB  - Proteins can be identified by rapid techniques that do not involve Edman
      degradation sequencing. These approaches entail the matching of amino acid
      compositions or tryptic peptide masses of proteins against databases, often in
      conjunction with estimated protein molecular weight and isoelectric point. As
      genome sequencing projects progress, proteins from poorly molecularly defined
      organisms will increasingly be identified by cross-species comparison to proteins
      from well-defined organisms. To investigate the application of rapid techniques
      for cross-species protein identification, a total of 65 theoretical cross-species
      comparisons involving 21 proteins (nine human and 12 E. coli) were undertaken.
      The degree of conservation of amino acid composition, tryptic peptides, protein
      isoelectric point and mass was established. Protein amino acid composition was
      well conserved across species boundaries, whilst tryptic peptides were poorly
      conserved. The molecular weight of proteins was generally well conserved, but
      protein isoelectric point was not. These results suggest that cross-species
      protein identification by rapid techniques will be done best by protein amino
      acid composition and protein molecular weight.

PMID- 9176635
TI  - Effect of pruning on dendritic tree topology.
AB  - The variability in topological shapes of observed neuronal branching patterns can
      accurately be described by a simple model for random sequential growth. This
      finding is remarkable in view of the fact that the actual neuritic growth process
      can vary, and includes phases of regression and removal of branches which were
      not considered in the model. The aim of the present study is to investigate the
      influence of removal of branches on the topological structure of branching
      patterns as well as the effect of variable growth rules. A tree asymmetry index
      is used for the characterization of the topological structure of a tree. The mean
      value of the asymmetry index for a set of dendritic trees is sensitive to the
      mode of growth. The effect of removal of branches ("pruning") on the topological
      structure of dendritic trees has been studied for several random pruning schemes,
      namely (i) removal of uniform randomly chosen subtrees, (ii) removal of uniform
      randomly chosen terminal segments, (iii) uniform random pruning during the growth
      process itself, and (iv) non-uniform random pruning schemes. It was found that
      the effect of pruning depends on both the mode of pruning and the mode of growth.
      Uniform random (terminal) pruning had no effect on the mean and standard
      deviation of the asymmetry index of trees grown with an order-independent mode of
      branching. Changes in the mean of the asymmetry index could occur either with non
      uniform random pruning or when trees are grown according to an order-dependent
      mode of branching. The effect of variable growth rules was studied for several
      specific schemes, and it could be shown that they all result in a substantial
      increase in the variation in the asymmetry index of the trees.

PMID- 9176636
TI  - Clonality and life cycles of intestinal crypts explained by a state dependent
      stochastic model of epithelial stem cell organization.
AB  - The organization and control of stem cells is a key issue in epithelial cell
      biology. The small intestinal murine crypt is a useful tissue to study such
      problems since stem cells are known to be located at specific positions at the
      bottom of the crypt where they are self maintaining. Recent data suggest, that
      (1) the number of active stem cells in a crypt can fluctuate, (2) the immediate
      progeny of a single stem cell can replace other stem cells eventually leading to
      monoclonality and (3) the life cycle of crypts may be linked to stem cell
      dynamics. It is the objective of this paper to suggest a stochastic state
      dependent model of stem cell and crypt growth which can explain and-link these
      phenomena into one comprehensive framework. Monte Carlo simulations are performed
      to show consistently with available data. The model explains the size
      distribution of small intestinal crypts in steady state, the observations of stem
      cell fluctuations and monoclonality conversion, recovery of the crypt population
      after moderate damage and the rate of crypt fission and extinction. The key
      assumption of this model is an autoregulatory control of stem cell growth.

PMID- 9176637
TI  - What exactly are genomes, genotypes and phenotypes? And what about phenomes?
AB  - The fundamental concepts of genome, genotype and phenotype are not defined in a
      satisfactory manner within the biological literature. Not only are there
      inconsistencies in usage between various authors, but even individual authors do
      not use these concepts in a consistent manner within their own writings. We have
      found at least five different notions of genome, seven of genotype, and five of
      phenotype current in the literature. Our goal is to clarify this situation by (a)
      defining clearly and precisely the notions of genetic complement, genome,
      genotype, phenetic complement, and phenotype; (b) examining that of phenome; and
      (c) analysing the logical structure of this family of concepts.

PMID- 9176638
TI  - Quantitative analysis of binding protein-mediated ABC transport systems.
AB  - We present a mathematical proof for the applicability of the Michaelis-Menten
      theory to the analysis of binding protein-dependent transport systems. Fitting
      the rate equation for transport of substrate to experimental data obtained with
      the Escherichia coli maltose system under conditions where the concentrations of
      the binding protein was varied, it was possible to determine without any further
      assumptions: (1) K1, the affinity constant of the binding protein towards its
      substrate; (2) K3, the affinity constant of the unloaded binding protein towards
      the membrane components; and (3) R, the concentration of the membrane component.
      This analysis allows determination of the alteration of KM and Vmax of the system
      at varying concentrations of binding protein.

PMID- 9176639
TI  - Regulation of complex host dynamics by a macroparasite.
AB  - The impact of a macroparasite on a host population which can exhibit highly
      complex dynamics is considered. We focus on the case where the host reproduces
      annually, in which case we couple within-season density dependent interactions
      with a discrete-time pulse to reflect seasonal reproduction. Results from
      analytic arguments, supported by extensive numerical simulations, indicate that
      within season parasite-induced host mortality is potentially capable of
      stabilising and simplifying host dynamics. Moreover, the interaction of
      demographic processes occurring on different time-scales is, in some cases,
      stabilising. In particular, parasite reduction in host frequency, which is a
      destabilising process in the May & Anderson continuous time model, is found to
      stabilise host macroparasite interactions under certain conditions. These results
      are discussed in an ecological context.

PMID- 9176640
TI  - Conduction block and chaotic dynamics in an asymmetrical model of coupled cardiac
      cells.
AB  - The initiation and propagation of the cardiac impulse depends on intrinsic
      properties of cells, geometrical arrangements, and intercellular coupling
      resistances. To address the issue of the interplay between these factors in a
      simple way, we have used a system, based on the van Capelle and Durrer model,
      including a pacemaker and a non-pacemaker cell linked by an ohmic coupling
      resistance. The influence of asymmetrical cell sizes and electronic load was
      investigated by using numerical simulations and continuation-bifurcation
      techniques. The loading of a small pacemaker cell by a large non-pacemaker one
      (pacemaker: non-pacemaker size ratio = 0.3) was expressed as a pronounced early
      repolarization in the pacemaker cell and a quite long latency for the impulse
      propagation. Using coupling resistance as the continuation parameter, three
      behavioral zones were detected from low to high coupling resistance values: a
      zone of total quiescence (0:0), a zone of effective entertainment (1:1), and a
      zone of total block (1:0 pattern). At the boundary between 1:1 and 1:0 patterns,
      for relatively high coupling resistance values, a cascade of period doubling
      bifurcations emerged, corresponding to discrete changes of propagation patterns
      leading into irregular dynamics. Another route to irregular dynamics was also
      observed in the parameter space. The high sensitivity of the detected irregular
      dynamics to initial conditions and the positive value of the maximum Lyapunov
      exponent allowed us to identify these dynamics as being chaotic. Since neither
      intermediate block patterns nor irregular dynamics were observed with larger size
      ratios, we suggest that the interplay between resting membrane conductance of the
      non-pacemaker cell and intercellular coupling may bring about these rhythmic
      disturbances.

PMID- 9176641
TI  - Modeling T-cell proliferation: an investigation of the consequences of the
      Hayflick limit.
AB  - Somatic cells, including immune cells such as T-cells have a limited capacity for
      proliferation and can only replicate for a finite number of generations (known as
      the Hayflick limit) before dying. In this paper we use mathematical models to
      investigate the consequences of introducing a Hayflick limit on the dynamics of T
      cells stimulated with specific antigen. We show that while the Hayflick limit
      does not alter the dynamics of T-cell response to antigen over the short term, it
      may have a profound effect on the long-term immune response. In particular we
      show that over the long term the Hayflick limit may be important in determining
      whether an immune response can be maintained to a persistent antigen (or
      parasite). The eventual outcome is determined by the magnitude of the Hayflick
      limit, the extent to which antigen reduces the input of T-cells from the thymus,
      and the rate of antigen-induced proliferation of T-cells. Counter to what might
      be expected we show that the persistence of an immune response (immune memory)
      requires the density of persistent antigen to be less than a defined threshold
      value. If the amount of persistent antigen (or parasite) is greater than this
      threshold value then immune memory will be relatively short lived. The
      consequences of this threshold for persistent mycobacterial and HIV infections
      and for the generation of vaccines are discussed.

PMID- 9176642
TI  - Nutritional support in advanced pulmonary disease.
AB  - Advanced pulmonary disease (APD), often secondary to emphysema or chronic
      bronchitis, is generally a progressive, incurable condition, ultimately leading
      to death. The condition is associated with significant, distressing symptoms.
      Most APD patients are underweight, which has numerous implications including
      accentuation of reduced physical capacity during daily life, increased risk of
      other secondary diseases, e.g. infections and osteoporosis, and a higher
      mortality during exacerbations with acute respiratory failure. Consequently,
      careful nutritional support is crucial both in enhancing physical well-being and
      function, and in reducing the risk of acute respiratory failure. Knowledge
      concerning the exact nutritional needs in APD is still very sparse; however,
      specific actions against malnutrition in APD patients should be mandatory in the
      treatment of APD. This paper reviews the literature concerning implications of
      malnutrition and benefits of nutritional support in APD patients, and gives
      suggestions for the practical, daily-life nutritional management of APD.

PMID- 9176643
TI  - Halothane administration during liquid ventilation.
AB  - The objective of this study was to test the hypothesis that perfluorochemical
      (PFC) liquid ventilation (LV) can be used as a vehicle to deliver halothane and
      induce and maintain analgesia. Seven hamsters were paralysed and stabilized with
      mechanical gas ventilation, ventilated in alternating cycles with gas and either
      neat oxygenated PFC liquid or oxygenated PFC liquid mixed with liquid halothane
      (PFC:hal) 1:50% (volume/vapour); arterial pressure and blood gases were monitored
      throughout the protocol. After each cycle, the animal was stimulated with a foot
      clamp for 2 s. Mean arterial pressure (MAP:mmHg) response to this stimulation
      (percent change from the resting MAP) was used as an index of analgesia. Mean
      arterial pressure was significantly lower during ventilation with PFC:hal (73 +/-
      7 SE) as compared with MAP during neat PFC (113 +/- 5 SE) or gas ventilation (107
      +/- SE). Mean arterial pressure response (% change in MAP from baseline) to foot
      clamp stimulation was significantly lower with PFC:hal ventilation (+ 12 +/- 5%
      SE) as compared with neat PFC (+ 28 +/- 8% SE) and gas ventilation (+ 29 +/- 9%
      SE). There was no statistically significant difference in resting MAP or MAP
      response to foot-clamp stimulation between cycles of ventilation with neat PFC
      alone or gas ventilation; arterial blood gases were not significantly different
      between modes of ventilation or levels of analgesia. The data indicate that
      halothane can be administered during LV while supporting gas exchange, and
      demonstrate the feasibility of inducing analgesia while using PFC LV techniques.

PMID- 9176644
TI  - Effect of alveolar volume on the interpretation of single breath DLCO.
AB  - Single-breath carbon monoxide diffusing capacity in the whole lung (DLCO) and per
      unit alveolar volume (DLCO/VA), as expressed in percentage of normal values, gave
      discordant results when VA of the patients was abnormal. It was hypothesized that
      normal reference values were inappropriate to interpret data collected in such
      patients. To substantiate this hypothesis, DLCO and DLCO/VA were measured in four
      groups: (1) normal volunteers in whom both indices were measured at five
      different VA; (2) patients with high VA; (3) emphysematous patients; and (4)
      patients with diffuse interstitial lung diseases (DILD). In normal subjects, DLCO
      increased and DLCO/VA decreased with VA. In patients with overinflated lungs, the
      percentage of DLCO was more increased than DLCO/VA. In the emphysematous
      patients, both indices were equally decreased. In patients with DILD, DLCO was
      significantly more decreased than DLCO/VA in those suffering from a restrictive
      pattern. Theoretical values were re-calculated taking into account their true VA
      and using the relationships observed between DLCO, DLCO/VA and VA. The
      divergences between DLCO and DLCO/VA were strongly minimized. Therefore, the
      authors suggest the need to correct theoretical formulas in the presence of a
      restrictive pattern.

PMID- 9176645
TI  - The effect of inhaled glucocorticosteroids in emphysema due to alpha1-antitrypsin
      deficiency.
AB  - Despite the success of inhaled steroids in controlling asthma, the benefit in
      patients with chronic obstructive pulmonary disease (COPD) remains controversial.
      Five subjects with moderate to severe emphysema due to alpha 1-antitrypsin
      deficiency (phenotype PiZ) were followed with daily home spirometry in a 2 x 8
      weeks, randomized double-blind, placebo-controlled, crossover study of inhaled
      budesonide 0.8 mg b.i.d. In three of the five patients, there was a statistically
      significant increase in the mean forced expiratory volume in 1 s (FEV1), and in
      two of these patients, there was also a statistically significant increase in the
      mean forced vital capacity (FVC) during budesonide treatment. A significant
      diurnal variation in FEV1 and FVC was found in three and two patients,
      respectively, but did not change significantly during treatment. These findings
      emphasize the need for renewed evaluation of inhaled steroids in the treatment of
      patients with emphysema, and indicate that individual patients may have
      significant clinical improvement.

PMID- 9176646
TI  - Diagnostic strategy for pulmonary tuberculosis in a low-incidence country:
      results of chest X-ray and sputum cultured for Mycobacterium tuberculosis.
AB  - The referral centre of tuberculosis in the municipality of Copenhagen, Denmark
      was the setting for this study, which aimed to assess the diagnostic strategy
      (chest X-ray and clinical mycobacteriology) in pulmonary tuberculosis. Patient
      records and chest X-rays were examined for all patients who had sputum or gastric
      lavage examined for Mycobacterium tuberculosis (Mtb) from 1 January 1992 to 30
      April 1994. All chest X-rays were re-evaluated by a trained lung specialist, who
      did not know the results of sputum culture. Evaluation was referred to one of
      seven X-ray categories, and compared to the results of culture. Culture of sputum
      or gastric lavage were positive for Mtb in 54 (14%) of 392 patients; in 61% of 59
      patients with X-ray changes thought to be due to tuberculosis (TB); in 20% of 51
      patients with X-ray changes compatible with TB; in 14% of 35 patients with
      previous TB and radiographically active TB; in 2% of 103 patients with previous
      TB, but not radiographically active TB; in 1% of 112 patients with X-ray changes
      thought to be due to other disease; and none out of 32 patients with normal X
      ray. Even in this highly selected material, it is relatively expensive to find
      the very few cases of active TB in patients with chest X-ray changes not
      suspected to be due to TB. It is recommended that: (1) examination of sputum for
      Mtb should always be preceded by X-ray of the chest in a low-prevalence country;
      (2) routine culture of sputum for Mtb is restricted to patients with X-ray
      changes typical or compatible with active TB; and (3) exceptions to this general
      rule should be made on the basis of the individual's clinical history.

PMID- 9176647
TI  - The adequacy of oxygenation in patients with hypoxic chronic obstructive
      pulmonary disease treated with long-term domiciliary oxygen.
AB  - Survival in patients with hypoxic chronic obstructive pulmonary disease (COPD) is
      improved by long-term oxygen therapy (LTOT). Such patients are known to
      desaturate during activity and at night. The aim of this study was to assess the
      adequacy of oxygenation in patients with COPD receiving LTOT. Oxygen saturation
      (SaO2) was measured at home over 24 h in 20 patients with hypoxic COPD receiving
      LTOT. Eleven had arterial oxygen partial pressure values (PaO2) > or = 8 kPa
      (Group 1) and nine had PaO2 < 8 kPa (Group 2), at rest, breathing oxygen. There
      was no difference in SaO2 during the day and night when breathing oxygen. In
      Group 1, SaO2 was > 90% for 78 +/- 24% of the 24-h period. Four patients spent
      between 75 and 90%, and three spent < 75% of the 24-h period with SaO2 > 90%. In
      Group 2, SaO2 was < 90% for 69 +/- 27% of the 24-h period (P = 0.02). Two
      patients spent between 75 and 90%, and four spent < 75% of the 24-h period with
      SaO2 > 90%. Measurements of SaO2 over 24 h in patients with hypoxic COPD, while
      breathing oxygen, add further information to arterial blood gas sampling on the
      adequacy of oxygenation, and reveal inadequate oxygenation in many patients.

PMID- 9176648
TI  - Overlooked inhaled foreign bodies: late sequelae and the likelihood of recovery.
AB  - The present paper describes eight patients (two teenagers and six adults) who had
      chronic symptoms (haemoptysis, cough, recurrent pneumonia) caused by foreign body
      (FB) inhalation which went undetected for 3 months to 25 yr. None of the patients
      had the usual predisposing conditions like mental retardation, seizures or brain
      tumour. The diagnosis of FB was made by radiography in one patient only.
      Computerized tomography visualized one FB (a beef bone), and bronchoscopy
      identified FB in another two patients. The remaining four cases were diagnosed at
      thoracotomy. Removal of FB was curative in three of five cases who required
      surgical resection for irreversible bronchiectatic changes. The severity of
      pulmonary changes correlated with duration of symptoms. It is concluded that
      chronic, unexplained respiratory symptoms should warrant further investigation to
      exclude FB despite negative history and normal chest radiography. Finding of
      granulation tissue or cicatricial stenosis of the bronchus could be the only clue
      to the presence of a FB. Early diagnosis would avoid irreversible parenchymal
      changes which necessitate lung resection.

PMID- 9176649
TI  - The development of the 'Quality-of-life for Respiratory Illness Questionnaire
      (QOL-RIQ)': a disease-specific quality-of-life questionnaire for patients with
      mild to moderate chronic non-specific lung disease.
AB  - Chronic non-specific lung disease (CNSLD) encompasses asthma as well as chronic
      obstructive pulmonary disease (COPD). Recently in health care, there has been
      increasing awareness in the functional, psychological and social aspects of the
      health of patients; their quality of life (QOL). Quality-of-life research
      addressing CNSLD patients has been rather underdeveloped for a long period of
      time. Recently, however, the importance of QOL is being increasingly recognized,
      and several research groups have started to study QOL in CNSLD patients in more
      detail. This paper describes the construction of a disease-specific QOL
      instrument for patients with mild to moderately severe CNSLD. Items relating to
      several domains of QOL were listed, and 171 CNSLD patients in general practice
      were asked how much of a problem each item had been (assessed on a seven-point
      Likert scale). After applying an item-selection procedure, a uni-dimensional QOL
      questionnaire was constructed consisting of 55 items divided into seven domain
      subscales: breathing problems, physical problems, emotions, situations triggering
      or enhancing breathing problems, general activities, daily and domestic
      activities, and social activities, relationships and sexuality. Reliability
      estimates of the domain subscales of the constructed questionnaire varied from
      0.68 to 0.89, and was 0.92 for the QOL for Respiratory Illness Questionnaire (QOL
      RIQ) total scale. A first impression of the construct validity of the
      questionnaire was gained by investigation of the relationship between the QOL
      domain subscales and several indicators of illness severity, as well as the
      relative contribution of illness severity variables, background characteristics
      and symptoms to QOL, using regression analysis. Further research to validate the
      questionnaire to a greater extent (construct validity, test-retest reliability
      and responsiveness to change) is currently taking place.

PMID- 9176650
TI  - The Spacehaler for delivery of salbutamol: a comparison with the standard metered
      dose inhaler plus Volumatic spacer device.
AB  - The Spacehaler is a new, compact, pressurized aerosol device that uses the same
      canister as a conventional metered-dose inhaler (MDI). Its design, however,
      reduces the velocity of the aerosol cloud that emerges from the inhaler, thereby
      reducing the amount of the non-respirable fraction of the drug delivered to the
      patient. Large volume spacers achieve a similar effect, but they are bulky and
      therefore inconvenient to use and carry around. This study compared the
      bronchodilator effect of 200 micrograms salbutamol delivered by the Spacehaler to
      that of an MDI used with a Volumatic spacer (MDI plus spacer) in patients with
      reversible obstructive airways disease. Twenty-five patients with asthma, having
      a forced expiratory volume in 1 s (FEV1) between 50 and 90% predicted and a
      reversibility of > or = 15% to 200 micrograms salbutamol given by the
      conventional (standard) MDI entered the study. On two separate study days, they
      inhaled 200 micrograms salbutamol either via the Spacehaler or the MDI plus
      spacer. To maintain blinding, they received placebo on both study days via the
      alternate device. Their FEV1, forced vital capacity (FVC) and peak expiratory
      flow (PEF) were measured before and at regular intervals for 6 h after
      inhalation. Assessment of equivalence between the two devices was based on
      whether the 90% confidence interval for the difference between the weighted mean
      FEV1 was within +/- 0.25 1. Patient preference was assessed by a questionnaire at
      the end of the second study day. Twenty-four patients completed the study. Both
      devices produced a significant improvement in FEV1 (P < 0.02). The upper and
      lower 90% confidence limits for the difference in weighted mean FEV1 between the
      devices was +/- 0.041, and the 99% confidence limits were +0.061 and -0.071. The
      weighted means for FVC and PEF, and the duration of effect and peak responses for
      FEV1, FVC and PEF also showed no difference between the two devices. Patients
      found no difficulty in using the Spacehaler, and 20 out of 24 patients (83.3%)
      preferred it to the MDI plus spacer. The bronchodilator effect of 200 micrograms
      salbutamol administered by a Spacehaler was equivalent to that produced by an MDI
      plus spacer in this group of patients with reversible airways obstruction. The
      majority of patients preferred it to a large volume spacer.

PMID- 9176651
TI  - Interleukin-8 and leukotriene B4 in bronchoalveolar lavage fluid from HIV
      infected patients with bacterial pneumonia.
AB  - Human immunodeficiency virus (HIV)-infected patients are at increased risk of
      contracting bacterial infections, mainly pneumonia. Despite this, little is known
      about immunopathogenic mechanisms in HIV-related bacterial pneumonia. This paper
      investigates the presence of the neutrophil chemotactic mediators, interleukin-8
      (IL_8) and leukotriene B4 (LTB4), in bronchoalveolar lavage (BAL) fluid from 27
      HIV-infected patients with bacterial pneumonia. Significantly elevated levels of
      IL-8 were found in BAL fluid of patients with bacterial pneumonia [529 pg ml-1
      (296-1161 pg ml-1)] compared to matched patients with Pneumocystis carinii
      pneumonia (PCP) [59 pg ml-1 (42-254 pg ml-1)] and healthy controls [58 pg ml-1
      (37-82 pg ml-1)]. Levels of LTB4 were not elevated during bacterial pneumonia
      when compared to PCP patients and healthy controls. Furthermore, a positive
      correlation was found between IL-8 levels in BAL fluid and relative BAL
      neutrophilia (r = 0.60, P = 0.001) in bacterial pneumonia. In conclusion,
      elevated IL-8 levels in BAL fluid were found in patients suffering from bacterial
      pneumonia, which may account for the influx of neutrophils to the lung, whereas
      LTB4 appears not to be an important chemotactic factor in this setting.

PMID- 9176652
TI  - Retention of titanium tetrafluoride (TiF4), used as fissure sealant on human
      deciduous molars.
AB  - When dental hard tissues are exposed to aqueous solutions of TiF4, an acid
      resistant glaze forms on tooth surfaces. The aim of the present study was to
      examine the long-term retention of the glaze on TiF4-treated deciduous molars.
      The occlusal surfaces of four deciduous molars in each of seven children were
      treated with 4% TiF4 for 1 min. The sealed teeth were extracted after 1, 3, 6, or
      12 months and examined with scanning electron microscopy. An extensive surface
      layer was present on all deciduous molars after 1 month. After 3 months the glaze
      appeared to be worn out on the cusp tips and in some areas on the cusp inclines.
      At 6 months the glaze was observed as small areas distributed over the cusp
      inclines with total coverage of the pits and fissures. After 1 year the presence
      of the glaze was limited to pits and fissures. Clinically, all fissures were
      caries-free by visual inspection at the end of the experimental period. The
      results indicate that the glaze formed after topical TiF4 application may be an
      effective way of sealing pits and fissures under clinical conditions.

PMID- 9176653
TI  - Base and fog densities of fresh Ektaspeed Plus dental X-ray films.
AB  - Previous findings with regard to base and fog density of Ektaspeed Plus dental X
      ray films have shown increased values compared with Ektaspeed and Ultra-Speed
      films, but the results are contradictory. The purpose of the present study was to
      measure base density, using 10 different fixing solutions, and fog density, using
      10 different developing solutions at temperatures varying from 16 to 30 degrees
      C. The 10 developers tested were intended for manual (three), semiautomatic
      (three), and automatic (four) processing. Base densities were nearly identical
      for all fixing products (range, 0.190-0.192). One group of six developers showed
      quite stable fog values for all temperatures (range, 0.190-0.259), whereas
      another group (four developers) showed increased values at increasing
      temperatures (range, 0.395-0.438 at 30 degrees C). It is concluded that base
      density is within the limits of ISO standards for most fixing products but that
      some developers result in fog densities that are above ISO standard limits at
      high temperatures.

PMID- 9176654
TI  - Salivary fluoride concentration in adults after different fluoride procedures.
AB  - Today, several alternatives for fluoride therapy are available. To give advice on
      the choice of method, the dentist should have information on how effective
      different fluoride treatments are in increasing salivary fluoride concentration.
      The aim of the present study was to measure the fluoride concentration of saliva
      after the use of four different fluoride methods commonly used in the Nordic
      countries: F mouthrinse (0.023% F), F toothpaste (1.1% F). F lozenge (0.25 mg F),
      and F chewing gum (0.25 mg F). In addition, a new method using toothpaste water
      mixture as a mouthrinse was included in the study. Fourteen adult volunteers used
      each of the five methods on separate days. Unstimulated saliva samples were
      collected at base line and 0, 10, 20, 30, 45, and 60 min after the fluoride
      procedure. Fluoride was separated by the microdiffusion method and analyzed using
      a fluoride-specific electrode. Fluoride mouthrinse and fluoride toothpaste
      increased the fluoride concentration of saliva significantly more than fluoride
      lozenge and fluoride chewing gum. For both of the latter, salivary fluoride
      concentration was still increased after 1 h. Toothpaste-water rinse was more
      effective than brushing with toothpaste. Rinsing with toothpaste-water mixture
      appears a good alternative for adults who need extra fluoride therapy but are not
      motivated enough to brush their teeth several times a day.

PMID- 9176655
TI  - Electric impedance measurements at six different anatomic locations of
      macroscopically normal human oral mucosa.
AB  - We have used an electric impedance technique to explore the properties of the
      oral mucosa at various sites in the normal mouth. Investigations were performed
      on 26 healthy non-smoking subjects at 12 test areas, representing a range of
      mucosal types. Electric impedance spectra were measured in the frequency range 1
      kHz to 1 MHz at five depth penetration settings of the instrument, and four
      indices were calculated for each depth. Statistically significant differences in
      the indices were found between most of these locations but not between
      contralateral sites at a similar position. The differences between some areas
      were considerably greater, and the differences between contralateral sites were
      smaller, than those encountered in the skin. Our results suggest that the choice
      of site for investigation of the oral cavity is more critical than with
      experimentation on the skin and that cognizance of this fact makes the oral
      cavity readily available for studies by the impedance method.

PMID- 9176656
TI  - Retention of propanal and diacetyl in experimental resins.
AB  - The degree of evaporation from experimental resins containing 0.40 mol% propanal
      or diacetyl was determined over a 6-month period at 60 degrees C. From the
      results the maximum evaporation possible, M infinity was calculated for each
      resin and was found to vary between 0.28% and 7.51% by weight. At low contents of
      propanal or diacetyl, M infinity 1 remained unchanged as compared with the
      control resins without additive. At higher contents of additive, M infinity
      increased significantly. In resins based on BisGMA and TEGDMA, propanal was
      retained to a lesser extent than diacetyl. In resins based on UEDMA and HEMA,
      propanal was retained to a greater extent than diacetyl. This study confirms that
      propanal and diacetyl become bound in the polymer structure, and theories as to
      the reaction mechanisms are presented.

PMID- 9176657
TI  - Prostaglandin E2 level in gingival crevicular fluid from patients with Down
      syndrome.
AB  - The levels of prostaglandin E2 (PGE2) and interleukin-1 beta (IL-1 beta) were
      determined in gingival crevicular fluid (GCF) collected from patients with
      gingivitis: 15 Down syndrome children and 15 controls. The mean level of PGE2 in
      GCF was significantly higher (P < 0.05) in the Down syndrome group (10.0
      pg/microliters GCF) than in the control group (4.6 pg/microliters GCF). In GCF
      samples collected from sites characterized as noninflamed, the mean level of PGE2
      was significantly higher (P < 0.001) in the Down syndrome group than in the
      controls. The mean level of PGE2 in samples from inflamed sites, on the other
      hand, did not differ between the two groups. The mean level of IL-1 beta was not
      significantly higher in the Down syndrome group than in the controls. This study
      shows that the level of PGE2 detected in GCF from Down syndrome patients is
      increased, a fact that may be of importance in the pathogenesis of the
      periodontal disease frequently seen in these patients.

PMID- 9176658
TI  - Determinants of self-assessed gingival health among adolescents.
AB  - The purpose of the present cross-sectional study was to assess the extent of
      agreement between clinical and self-assessed gingival health and to investigate
      possible factors associated with the amount of self-assessed gingival bleeding. A
      study group comprising students enrolled in grade 7 or 8 in Helsinki, Finland (n
      = 172), performed a self-assessment based on two tests: the amount of bleeding
      after toothbrushing and after interproximal tooth cleaning with toothpicks.
      Clinical examinations based on bleeding on probing (BOP%) were carried out by
      four local community dentists. The highest observed kappa value was 0.43 for the
      agreement between BOP% and self-assessment when tested with different cut-off
      points of diagnosis. Multivariate analysis showed that clinical status and
      toothbrushing frequency were statistically significantly associated with self
      assessed gingival bleeding in both tests. Socioeconomic status and locus of
      control orientation were also statistically significant factors in the toothpick
      test. In conclusion, the validity of self-assessment of bleeding was sufficient
      for monitoring adolescents' gingival health in groups. Self-assessed bleeding was
      explained by the same factors that were associated with clinical gingival health
      status.

PMID- 9176659
TI  - Oral sugar clearance and other caries-related factors in patients with myotonic
      dystrophy.
AB  - The aim of the investigation was to try to explain why patients with myotonic
      dystrophy (MD) have a high caries prevalence. Seventeen MD patients, 15 of whom
      had been examined 8 years earlier, and 17 matched, healthy controls participated.
      In connection with this follow-up examination, the oral sugar clearance was
      evaluated after chewing a glucose tablet. A paraffin-stimulated whole saliva
      sample was collected for determination of secretion rate, buffer capacity, and
      numbers of mutans streptococci and lactobacilli. Dietary score, plaque index,
      oral muscular coordination, and self-cleaning ability were also recorded. For all
      factors, the MD patients showed less favorable mean values than the controls; the
      differences between the groups were statistically significant, except for the
      bacterial counts and the salivary buffer capacity. Thus, the high caries
      prevalence in MD patients may be explained by longer oral sugar clearance time,
      lower salivary secretion rate, higher intake frequency of sugar-containing
      products, higher plaque index, and less pronounced oral muscular coordination and
      self-cleaning ability than in healthy individuals.

PMID- 9176660
TI  - Dentist-patient communication: a review of relevant models.
AB  - A review of the literature on dental treatment was conducted and models presented
      of the doctor/dentist-patient relationship. These models are listed and divided
      into two subgroups, empirical and normative models. The models are scrutinized
      with focus on the dentist-patient communicative relationship exclusively.
      Different doctor/dentist-patient relationships are described. External factors
      influencing these relationships are defined. An analysis of dentist-patient
      communication is made, and a new model of dentist-patient communication is
      suggested, which states that what is done and what is said during dentist-patient
      encounters will have an impact on outcome. Three different purposes of dentist
      patient communication are presented. The process of attaining these is discussed.
      It is concluded that a theory of communication is lacking in the dental context,
      and the need to develop a reliable and valid interaction analysis system for the
      patient-dentist communication is confirmed.

PMID- 9176662
TI  - Skin reactions and irritation potential of four commercial toothpastes.
AB  - Skin reactions to 4 toothpastes were tested in 19 healthy dental students in a
      double-blind study. The hypothesis was that common toothpaste brands with and
      without sodium lauryl sulfate (SLS) and triclosan and with different
      additives/emulgators differ in irritation potential. An occlusion test system on
      human skin was used. The toothpastes tested were A) Zendium (non-ionic
      detergent), B) Solidox F (SLS/polyethylene glycol), C) Colgate Total
      (triclosan/copolymer/SLS/propylene glycol), and D) Solidox G (triclosan/zinc
      citrate/SLS/polyethylene glycol). Toothpaste C was the greatest irritant, causing
      skin erythema in 16 of the 19 subjects, whereas toothpaste D gave no reactions.
      Toothpaste B provoked three reactions (two severe), whereas toothpaste A caused
      only one mild reaction. Although this study was carried out on skin and hence not
      directly applicable to the oral cavity, these and previous results may indicate
      that a toothpaste without propylene glycol and SLS may be preferred by
      susceptible persons.

PMID- 9176661
TI  - Oral disease, impairment, and illness: congruence between clinical and
      questionnaire findings.
AB  - In 1992 a questionnaire was sent to 50-year-olds in two Swedish counties. These
      self-report data were compared with clinical observations with regard to number
      of teeth, removable dentures, caries, and periodontitis. Complete information
      from both data sources was obtained for 1041 persons. The relevant questionnaire
      item explained 71% of the missing tooth variance. An agreement of 0.91 (Cohen's
      kappa) was obtained for removable dentures. A question about problems in opening
      the mouth differentiated clearly with regard to measured mouth opening ability.
      Toothache and tooth sensitivity were reported with 95% probability when having 22
      decayed teeth and with 46% when there were no decayed teeth (58% correctly
      predicted). Two teeth with pockets > or = 6 mm gave 5% probability and 22 such
      teeth gave 39% probability of reporting migration of front teeth. The main
      conclusion from this study is that there is good correspondence between
      subjective self-reports and clinical findings, especially for those conditions
      that are relatively easy for the patient to observe, such as the number of teeth
      and the presence of dentures. Thus questionnaire data can be used for information
      and screening about some well-defined oral conditions.

PMID- 9176663
TI  - Fine structure of the choroidal coat of the avian eye. Vascularization,
      supporting tissue and innervation.
AB  - To clarify further the functional anatomy of the avian choroid, including its
      innervation, 12 adult White-Leghorn chickens were studied by standard electron
      microscopy and immunoelectron microscopy with somatostatin antibody. The
      endothelial cells of the blood vessels in the choriocapillaris have fenestrations
      only facing the retina, while the nuclei are situated toward the sclera. In
      addition to tight junctions and zonulae adherentes, adjoining endothelial cells
      form gap junctions and dense plaques with attached filaments resembling those of
      smooth muscle cells. The fine structure of arteries and veins is similar to that
      of the vasculature described in other organs. The supporting tissue is organized
      in trabeculae, i.e., bridges of cellular and fibrous elements that surround and
      sustain blood and lymphatic vessels. This tissue consists primarily of a system
      of fusiform or star-shaped smooth muscle cells, connected to each other and to
      those in the vessels' walls through macular junctions of the adherent type, less
      prominent than desmosomes, and perhaps also punctiform gap junctions.
      Occasionally, trabecular smooth muscle cells approach the lymphatic vessels,
      which lack a muscular tunica, and abut their endothelium with spinous appendages.
      This stromal muscle tissue may act as a pump for moving the lymph. The
      suprachoroidea consists of large lymphatic lacunae and the multilayered membrana
      fusca. The elongated fuscal cells form adherent junctions, tight junctions, and
      perhaps also gap junctions, suggesting that the membrana fusca exerts complex
      functions. Nerves containing myelinated axons reach the choroid and divide into
      smaller branches, a few of which innervate the membrana fusca. Numerous, thin
      nerve branches reach both the walls of arteries and veins and the trabeculae, and
      synaptic terminals abut the outer muscular layers of the vessel's wall and the
      smooth muscle cells of the supporting tissue. Immunocytochemistry reveals the
      presence of numerous somatostatin-positive and somatostatin-negative axons and
      synaptic terminals within both trabeculae and vascular tunica media. The
      somatostatin-positive axons are presumed to be cholinergic axons of the choroid
      neurons residing in the ciliary ganglion. Taken together, these observations
      indicate that the avian choroid is a highly vascularized muscular sheath that may
      be endowed with degrees of motility and elasticity higher than those of the
      mammalian choroid and may therefore play an important role in compensation for
      experimental defocus.

PMID- 9176664
TI  - Ncx, a Hox11 related gene, is expressed in a variety of tissues derived from
      neural crest cells.
AB  - We have isolated the murine homeobox gene (Ncx) that belong to a Hox11 gene
      family. Expression of the Ncx gene was analyzed in total RNAs from embryos by
      reverse transcribed polymerase chain reaction (RT-PCR). The mRNA was detected in
      embryos after 9.5 days of embryogenesis (E9.5) and was maximal at E12.5. The RT
      PCR also detected the message in total RNAs from adrenal glands and intestine in
      adult mice. The expression was further examined in various tissues from embryos
      by in situ hybridization. It was detected in dorsal root ganglia, cranial nerve
      ganglia (V, IX, X), enteric nerve ganglia and adrenal glands from embryos between
      E9.5 and E13.5. Since its expression is restricted to tissues derived from neural
      crest cells, Ncx may play a role in differentiation and proliferation of neural
      crest lineage cells.

PMID- 9176665
TI  - Cell death during tooth eruption in the rat: surrounding tissues of the crown.
AB  - We investigated the occurrence of apoptosis and other types of cell death around
      the crown during tooth eruption of the rat upper molar. The TdT-mediated-dUTP
      biotin nick end labeling (TUNEL) method and transmission electron microscopy
      (TEM) were employed. Apoptosis was detected by both TUNEL and TEM in part of the
      reduced enamel epithelium and connective tissue in the resorbing bony crypt of
      the pre-erupted tooth. In TEM, a large number of cells showed condensed chromatin
      and membrane-bound small bodies (apoptotic bodies). Macrophages that phagocytosed
      apoptotic bodies could be detected. Based upon the distance between bone surface
      and these apoptotic cells, and the characteristics of their organelles, we
      suggested that the apoptotic cells might be osteocytes, bone-lining cells
      (osteoblasts), and macrophages. We surmised that the osteoclasts had also died.
      Cells which contained autophagic vacuoles and autophagosomes, and others whose
      cytoplasm had dissolved, were also frequently observed. No progressive cell death
      was found in the oral epithelium or the fibrous connective tissue over the crown.
      These results suggest that apoptosis gives rise to some cell death during tooth
      eruption, but that other types of cell death also occur in various cells.

PMID- 9176666
TI  - The fate of the first avian somite.
AB  - We have studied the derivatives of the first somite using the quail-chick marking
      technique. After transplantation of the somite, the chick embryos were
      reincubated for periods ranging from 4 h to 11 days. Coronal and sagittal
      sections of the embryos were prepared for parallel staining with Feulgen
      reaction, anti-quail antibody, anti-desmin antibody and QH-1 antibody. The first
      somite consists of an epithelial envelope surrounding somitocoele cells. Like
      other somites, it forms sclerotome, dermatome and myotome. Cells contribute to
      the occipital and parasphenoid bone, the meninges, the dermis in the occipital
      region and the pharyngeal connective tissue. The contribution of the first somite
      to bones, meninges, dermis and pharyngeal connective tissue is characterised by
      sharp anterior and posterior boundaries. In contrast, other derivatives such as
      connective tissue surrounding the vagus nerve, the carotid artery, and jugular
      vein exceed 10 to 18 segments. This is also true for myogenic cells participating
      in the formation of the cucullaris capitis muscle that extends from the temporal
      bone to the shoulder. In one third of the embryos, myocytes of the intrinsic
      laryngeal muscles are derived from the grafted first somite. Moreover,
      endothelial cells originate from this somite and migrate into the head (hind
      brain, meninges, dermis), neck (pharynx, connective tissue surrounding the vagus
      nerve, carotid artery and jugular vein) and thorax. With respect to
      differentiation and derivatives the first somite is similar to other somites.

PMID- 9176667
TI  - Immunocytochemical localization of mu-opioid receptors in follicular cells and
      preimplantation mouse embryos.
AB  - It has been demonstrated that opioid peptides are involved in the regulation of
      mammalian reproduction. In our previous studies we demonstrated direct effects of
      opioids on preimplantation mouse embryos, and hypothesized the existence in
      preimplantation embryos of receptors similar to opioid receptors in the central
      neuronal system of adult animals. In the present study we addressed this issue by
      employing immunocytochemical staining for mu-opioid receptors using antisera
      raised against the C-terminal portion of the cloned mu-opioid receptors (MOR1,
      NHQLENLEAETAPLP, 384-398) predicted from the cloned receptor. Diffuse MOR1
      immunoreactivity of moderate intensity has been revealed in one-cell embryos,
      while in follicular cells MOR1 staining was of high intensity and appeared to be
      associated with plasma membrane. No MOR1 immunoreactivity has been observed in
      two-cell to morula stages of development. However, blastocysts displayed intense
      MOR1-labeling that was particularly prominent in cells within the inner cell
      mass. MOR1-staining was most likely specific because preincubation of MOR1
      antisera with cognate peptide completely abolished the staining. Our findings
      suggest the presence of opioid receptors during preimplantation development, long
      before the formation of the nervous system. Embryonic opioid receptors may play a
      role in the regulation of preimplantation development and implantation.

PMID- 9176669
TI  - Postimplantation development of mouse blastocysts with two separate inner cell
      masses.
AB  - Blastocysts with double inner cell masses (ICMs) were produced by electrofusion
      of two blastocysts and transplanted to pseudopregnant recipients. The implanted
      embryos were either examined histologically (8th day of pregnancy) or dissected
      and inspected in toto (11th or 12th day). In most cases both ICMs of experimental
      blastocysts developed into separate egg cylinders. Both cylinders were located in
      the common yolk sac cavity. Some cylinders were quite normal, but most of them
      were small and deprived of embryonic membranes. Ectoplacental cones of these
      cylinders were often oriented laterally or even antimesometrially. The
      development of cylinders seems to depend upon the position of their ectoplacental
      cones--cylinders with cones situated antimesometrially were handicapped in
      development. Among four sets of twin embryos examined on the 11th or 12th day, in
      one set each of the twins were equally developed, and in the three others one of
      the twins was more advanced.

PMID- 9176670
TI  - Ultrastructural characteristics of primordial germ cells and their amoeboid
      movement to the gonadal ridges in the tammar wallaby.
AB  - The primordial germ cells (PGCs) of tammar wallaby fetuses are large cells with
      large nuclei. The cytoplasm of the PGCs contains characteristic spherical
      mitochondria and abundant ribosomes that make the cyoplasm appear dense. No
      permanent junctional complexes between PGCs and somatic cells were observed, and
      there were few cytoplasmic inclusions. The majority of migrating PGCs were
      observed outside the gonad in the dorsal mesentery and in the tissues adjacent to
      the gonad. The migrating PGCs have many finger-like, blunt pseudopodia, within
      which microfilament bundles are observed. The numerous dumbell-like PGCs with
      polarised cytoplasm suggest that the PGCs of this marsupial move to the gonadal
      ridges by amoeboid movement, but once the PGCs reach the gonadal ridge, they
      assume their more characteristic ovoid shape.

PMID- 9176668
TI  - Close link between cutaneous nerve pattern development and feather morphogenesis
      demonstrated by experimental production of neo-apteria and ectopic feathers:
      implication of chondroitin sulphate proteoglycans and other matrix molecules.
AB  - In chick skin, nerve arcades develop around the base of feathers. In order to
      understand the mechanisms of their formation, we have tried to dissociate arcade
      formation from feather morphogenesis in various ways. Nerve patterns were
      analysed (1) in hydrocortisone-treated embryos that are partially devoid of
      feathers, (2) after retinoic acid treatment that produces ectopic feathers, (3)
      in dorsal root ganglia-skin co-cultures. Whenever tested, immunochemistry
      revealed that nerve arcades form around chondroitin sulphate proteoglycan-rich
      areas. Hydrocortisone treatment modifies the distribution of two out of three
      chondroitin sulphate proteoglycan epitopes tested, as well as the shapes of the
      feathers and nerve arcades, but not fibronectin, tenascin or laminin
      localizations. Chondroitinase digestion in co-cultures eliminated the nerve
      arcade formation and produced abnormally thin feathers, but nevertheless with a
      normal spatial distribution. Thus, chondroitin sulphate proteoglycans are
      probably not involved in the overall arrangement of feathers, but appear to play
      a fundamental role in both the formation of nerve arcades and the morphogenesis
      of the feather.

PMID- 9176671
TI  - Newer surgical techniques in urology.

PMID- 9176672
TI  - Presentation of the 1996 Herman Wacker Prize to Pierre Amalric, MD.

PMID- 9176673
TI  - 1996 Jules Gonin Lecture of the Retina Research Foundation. Long-term results
      after proton irradiation of uveal melanomas.

PMID- 9176674
TI  - Characterization of epithelial primary cultures from human conjunctiva.
AB  - Primary cultures of human epithelial cells from normal conjunctiva were developed
      and characterized to determine whether they retained epithelial characteristics.
      Conjunctival explants were obtained from the upper fornix of healthy donors and
      cultured in supplemented DMEM/F-12 medium for 5 days. The epithelial outgrowth
      was maintained for an additional 10 days. Primary cultures were then processed
      for light microscopy, transmission and scanning electron microscopy (TEM, SEM),
      and immunocytochemistry. They exhibited typical features of conjunctival
      epithelium on light microscopy (polygonal morphology, intimate cohesion,
      production of mucins), TEM (abundant desmosomes, keratin bundles, granules,
      microvilli), SEM (polygonal shape, microvilli, intimate cohesion), and
      immunocytochemistry (positivity for the receptor of epidermal growth factor,
      desmosomal proteins, and cytokeratins). In conclusion, primary cultures developed
      from normal human conjunctiva maintained the epithelial characteristics in vitro.
      Because the conjunctiva is a major component of the anterior ocular surface, we
      propose this in vitro system as suitable for physiopathologic and toxicologic
      studies.

PMID- 9176675
TI  - A comparison of blood pressure changes in phacoemulsification cataract surgery
      with topical and retrobulbar block local anesthesia.
AB  - BACKGROUND: Changes are observed in blood pressure (BP) levels during cataract
      surgery, although BPs are considered to remain stable under local anesthesia. We
      evaluated the daily, pre- and postoperative BPs of 2270 patients after cataract
      surgery performed under either topical anesthesia or retrobulbar block. METHODS:
      All operations were performed by the same surgeon using the same method of
      phacoemulsification and aspiration with posterior chamber intraocular lens
      implantation under local anesthesia. RESULTS: The mean daily BP was 99.3 +/- 14.2
      mm Hg; the mean preoperative BPs increased and then the postoperative BPs
      decreased. The postoperative BPs of the retrobulbar injection group decreased
      significantly more than those of the topical application group. In 833 cases, the
      systolic BP changed by more than 20 mm Hg. Even when the patients were
      hypertensive, the preoperative and postoperative BPs decreased in the same
      manner. CONCLUSION: The present study shows that, following surgery with
      retrobulbar block anesthesia, BP decreases to a greater extent than with topical
      anesthesia. Physicians should be aware of the high proportion of cases in which
      the systolic BP changes by more than 20 mm Hg.

PMID- 9176676
TI  - Fundus pulsation measurements in diabetic retinopathy.
AB  - BACKGROUND: There is experimental evidence that retinal blood flow is impaired in
      patients with diabetes mellitus. Much less attention has been paid to choroidal
      blood flow. Hence it was the aim of the present study to investigate choroidal
      blood flow in diabetic retinopathy. METHODS: A new non-invasive laser
      interferometric technique was used to measure fundus pulsations in the macula.
      The fundus pulsation amplitude, which is the maximum distance change between
      cornea and retina during the cardiac cycle, is a measure of local pulsatile blood
      flow. The eyes (n = 214) were divided into four groups according to the modified
      Airlie House classification: (1) no retinopathy (control group), (2) background
      retinopathy, (3) moderate to severe preproliferative retinopathy, (4)
      proliferative retinopathy. In 83 eyes of different group fundus pulsation
      measurements were repeated after 1-6 weeks. RESULTS: Fundus pulsation amplitudes
      were significantly smaller in group 4 than in the control group (P < 0.027). The
      reproducibility of the measurements was high and did not differ among the study
      groups. CONCLUSIONS: Local fundus pulsations in the macula are reduced in
      proliferative diabetic retinopathy, which is compatible with previous findings of
      reduced choroidal blood flow in late stages of the disease. Laser interferometric
      measurement of fundus pulsations is non-contactile, assures optimal comfort for
      the patient and could be used for the long-term observation of patients with
      diabetes mellitus.

PMID- 9176677
TI  - Orbital exenteration: surgical and reconstructive strategies.
AB  - BACKGROUND: Radical exenteration procedures, which include the removal of orbital
      content and eyelids, result in serious functional limitations, especially with
      respect to eating and speaking. Therefore we have recently changed our surgical
      concept. METHODS: Seventy-seven patients underwent orbital exenteration during
      the 20-year period from 1974 to 1995 at the Department of Maxillofacial Surgery,
      Essen University. The simultaneous removal of periorbital bone was performed in
      45 of these cases. RESULTS: The 1-year survival rate was 89%, the 5-year rate was
      63% and the 10-year rate was 48%. The surgical approach, the amount of resected
      orbital tissue and the reconstructive procedure have been adapted to the
      individual needs, depending on the location and extent of the tumor.
      Subsequently, the surgical morbidity has decreased. DISCUSSION: Detailed
      consideration of all clinical and histological findings is essential before
      surgery, in order to prevent a higher rate of recurrence following these modified
      operations.

PMID- 9176678
TI  - Therapeutic use of the 193-nm excimer laser in corneal pathologies.
AB  - PURPOSE: To analyze the results of phototherapeutic keratectomy. PATIENTS AND
      METHODS: We performed 193-nm excimer laser phototherapeutic keratectomy (PTK) in
      252 eyes of 216 patients suffering from pain and/or decrease in visual acuity.
      One hundred and three eyes had recurrent erosions of the cornea, 86 eyes
      underwent excimer laser smoothing of the cornea after pterygium surgery, 29 eyes
      had a bandlike keratopathy (25 rough, 4 smooth) and 34 eyes had other pathologic
      conditions such as amyloidosis of the cornea, anterior corneal dystrophies, scars
      after injuries, alkali burns, superficial stromal dystrophies and infections.
      Recurrent erosions and epithelial dystrophies were treated with 15-20 pulses (160
      200 mJ/cm2, 8 mm ablation zone) after mechanical abrasion of the epithelium.
      Removal of corneal opacities and scars required the use of a masking fluid
      (methyl-cellulose) in different concentrations and slit-lamp control (integrated
      in the delivery system of the excimer laser). RESULTS: Some 91% of the eyes with
      recurrent erosions were recurrence-free. Fifty-two per cent of the eyes with
      pterygium had recurrences if the baresclera technique was used and 33% of the
      eyes if a free conjunctival graft was used. The difference was not significant.
      All of the patients with bandlike keratopathy were pain-free. In 88% of the eyes
      with special indications the treatment goal was achieved. No positive effect was
      seen after alkali burn, in a patient with anterior membrane dystrophy (Grayson
      Wilbrandt corneal dystrophy) or in a patient with a corneal protuberance. In one
      patient with scleroperikeratitis a late recurrence of the opacity was observed 3
      years after surgery. A loss of best corrected visual acuity was found only in one
      patient with bullous keratopathy in whom the treatment goal was the reduction of
      pain. All patients with smooth bandlike keratopathy had an improvement in best
      corrected visual acuity of at least one line. About 70% of patients with special
      indications improved by at least one line, up to nine lines. A possible hyperopic
      shift in all groups could be minimized using a large ablation zone. CONCLUSION:
      PTK with the 193-nm excimer laser is a safe and effective treatment for many
      superficial diseases of the cornea.

PMID- 9176679
TI  - Photoreceptor decay over time and apoptosis in experimental retinal detachment.
AB  - BACKGROUND: Data are scarce on the actual rate and mode of outer nuclear layer
      decay in retinal detachment (RD). We used an experimental rabbit model to assess
      the presence of apoptosis and rate of photoreceptor death following RD. This
      model included the creation of localized and stable retinal blebs, while
      controlling for any decline of retinal elevation over time. METHODS: RD was
      produced in New Zealand white rabbits by injecting 0.05 ml of 15% sodium
      hyaluronate (Healon GV) under the neural retina using a microsurgical technique.
      Animals were killed at 1, 2, 4, 7, 14 and 29 days. Retinal tissue was processed
      for light and electron microscopy and for in situ end labeling of fragmented DNA
      using a modification of the TUNEL technique. Photoreceptor cell nuclei were
      counted in the RD areas of maximum retinal elevation of 28 eyes, and an
      additional 4 eyes were used for nick end labeling. RESULTS: Positive DNA nick end
      labeling, ultrastructural features and absence of necrotic cells indicated
      apoptotic photoreceptor cell death. Also, there was a rapid, almost linear
      elimination of photoreceptor nuclei over time. At 14 days only half of the number
      of nuclei were discernible, while approximately one tenth remained after 29 days.
      There was a statistically significant, but minimal decline in RD height over the
      4 weeks of study. CONCLUSION: Following experimental RD in rabbits, apoptotic
      cell death is associated with an almost linear elimination of photoreceptor cells
      over time. The use of highly viscous sodium hyaluronate in separating the neural
      retina from the retinal pigment epithelium allows the RD to maintain a nearly
      constant height over a period of 4 weeks.

PMID- 9176680
TI  - Vascular endothelial growth factor expression in choroidal neovascularization in
      rats.
AB  - BACKGROUND: The pathogenesis of choroidal neovascularization is largely unknown.
      We investigated vascular endothelial growth factor (VEGF) expression in laser
      induced choroidal neovascularization (CNV) in rats. METHODS: Intense krypton
      laser photocoagulation was applied to the posterior poles of the eyes of
      pigmented rats to induce CNV, which was confirmed by fluorescein angiography and
      histopathology. The eyeballs were enucleated 1, 3, 7, 14 and 28 days after laser
      photocoagulation. Cryostat sections were prepared for immunofluorescence staining
      using anti-VEGF and macrophage marker (ED1) antibodies. The posterior segments of
      eyeballs pooled from photocoagulated and control rats were submitted for
      immunoprecipitation and immunoblotting by the anti-VEGF antibody, and reverse
      transcriptase-polymerase chain reaction (RT-PCR) amplification of VEGF mRNA.
      RESULTS: Very weak immunoreactivity for anti-VEGF antibody was found in the
      ganglion cell layer, inner nuclear layer, and retinal pigment epithelium (RPE) in
      the normal retina. In the development of CNV, strong positive staining for anti
      VEGF antibody was found in photocoagulated areas in the subretinal space and
      choroid. Double immunofluorescence staining showed that many cells in lasered
      lesions were positive both for anti-VEGF and macrophage marker ED1 antibody
      staining in the early stage of this model. Immunoblots showed a positive band for
      the VEGF molecule in treated but not control animals. RT-PCR results demonstrated
      upregulation of VEGF transcripts in the CNV model compared with normal animals.
      CONCLUSIONS: Our findings showed the upregulation of VEGF expression in
      experimentally induced CNV, where it may be involved in promoting choroidal
      angiogenesis. Macrophages may be one of the main sources of VEGF in the early
      stage of the disease.

PMID- 9176681
TI  - Retinal function with lens-induced myopia compared with form-deprivation myopia
      in chicks.
AB  - BACKGROUND: The retina is known to be involved in the development of form
      deprivation myopia (FDM); however, it is not clear whether the retinal changes
      that lead to lens-induced myopia (LIM) are the same as those involved in FDM. To
      gain insight into the retinal mechanism(s) that cause myopia, we investigated
      differences in the results of electroretinography (ERG) in eyes with FDM and LIM.
      METHODS: LIM or FDM was induced in chick eyes by placing various powers of
      spectacles or an occluder over the left eyes of 6-day-old chicks. After 6 days,
      the spectacles or occluder was removed, refraction and axial length were measured
      and ERG was performed. Results for eyes treated with spectacles and those treated
      with occluders were compared. RESULTS: Refraction and axial length changed
      concomitant with the power of the lens used, but components of the ERG of eyes
      with LIM were not related to the power of lens added. Refraction and axial
      lengths of eyes covered with a -16 D lens did not differ from these values in
      eyes covered with an occluder. The a- and b-waves were also similar for the two
      groups. However, oscillatory potentials decreased significantly in the chicks
      with FDM. CONCLUSIONS: Retinal function differs in LIM and FDM, as indicated by
      differences in the oscillatory potentials. This difference may stem from the fact
      that in FDM the retinal image is continuously defocused, whereas images are
      ultimately focused on the retina in LIM.

PMID- 9176682
TI  - Effect of corticosteroids on healing of the corneal endothelium in cats.
AB  - BACKGROUND: Anterior segment surgery is frequently complicated by damage to the
      corneal endothelium. We examined the effects of corticosteroids, which are widely
      used for the suppression of postoperative inflammation, on the process of
      endothelial cell regeneration. METHODS: The effect of corticosteroids on healing
      of the corneal endothelium was examined in 10 domestic cats. In both eyes a
      circular area, 8 mm in diameter, was scraped off at the center of the corneal
      endothelium without damaging Descemet's membrane. Immediately after scraping, as
      well as 2 and 5 days later, each animal received a unilateral retrobulbar
      injection of betamethasone sodium phosphate (2 mg). The other eye served as a
      control and received a retrobulbar injection of the vehicle only. RESULTS:
      Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed
      that relative to the control contralateral eyes, the corticosteroid-treated eyes
      exhibited a higher mean coefficient of variation of the corneal endothelium cell
      area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4 7 and 8
      cellular facets, thinner corneas and less inflammation. CONCLUSIONS: These
      findings suggest that corticosteroids unfavorably affect the regeneration of
      corneal endothelial cells after injury. As corticosteroids appear to have both
      positive and adverse effects on corneal function after trauma, they should be
      used with caution.

PMID- 9176683
TI  - Indocyanine green angiography in choroidal osteoma.
AB  - BACKGROUND: Choroidal osteoma is a rare choroidal tumor; knowledge of its
      indocyanine green characteristics is limited. METHODS: The fundus photographs and
      the fluorescein and indocyanine green angiograms of three patients were reviewed.
      Each patient was examined at least twice with a follow-up varying from 10 to 60
      months. RESULTS: Late-phase fluorescein angiograms allow assessment of the
      extension of the osteoma as it is variably hyperfluorescent due to tumor staining
      combined with a variable degree of overlying retinal pigment epithelial changes.
      The hypofluorescent area observed in the early phase of the indocyanine green
      angiogram corresponds with the extent of the osteoma but the borders may be
      difficult to demarcate. In the late phase of the indocyanine green angiogram,
      hypofluorescence due to choriocapillaris loss and hyperfluorescence due to
      leakage from abnormal choroidal vessels are combined. Infrared angiography high
      lights abnormal choroidal vessels and vascular spiders present on the tumor
      surface. It is difficult to differentiate these choroidal vascular anomalies from
      subretinal neovascularization. CONCLUSIONS: We find no homogeneous pattern either
      on fluorescein or on infrared angiography. The findings may change with follow
      up, indicating changes within the tumor or the surrounding tissue that are still
      poorly understood.

PMID- 9176684
TI  - Older adults' symptoms and their duration before hospitalization for heart
      failure.
AB  - OBJECTIVE: To describe the older adult heart failure patients' symptoms and their
      duration before a hospital admission and to explore related factors. DESIGN: The
      study was an archival study of inpatient hospital records at one acute care
      facility in western New York. SAMPLE: One hundred eighty-one patients with a mean
      age of 76 years. RESULT: Ninety-one percent of the patients reported having
      dyspnea an average of 3 days before hospital admission, and 37% reported having
      acute dyspnea an average of 12 hours before admission. Thirty-five percent of the
      patients reported having edema, and 33% reported a cough for an average of 7 days
      before their hospital admission. Age, heart failure history, and a symptom
      pattern of simultaneous development of preadmission symptoms were each related to
      the length of time patients experienced symptoms before admission. CONCLUSION:
      This study, at one acute care institution, showed that older adult patients with
      heart failure experience symptoms for a relatively long time before hospital
      admission. Education about symptom monitoring, symptom interpretation, and prompt
      health care-seeking are warranted for all patients with heart failure.

PMID- 9176685
TI  - The relationship between hospital length of stay and rate of death in heart
      failure.
AB  - OBJECTIVE: To study the relationship between length of stay (LOS) and the rate of
      death among patients hospitalized with congestive heart failure (CHF). DESIGN: A
      retrospective, observational study. SETTING: Fifteen acute care community
      hospitals in upstate New York. PATIENTS: Three thousand nine hundred fourteen
      patients whose principal billing diagnosis was diagnosis-related group number 127
      (CHF and shock). OUTCOME MEASURES: Mean total LOS and hospital death rate.
      VARIABLES: Mean number of nonacute care hospital days per patient, mean number of
      acute care days (acute LOS) per patient, cases per hospital, hospital bed
      capacity, and the presence of a cardiac catheterization laboratory, cardiac
      surgical services, or a medical residency training program. An index of severity
      of illness and a severity-weighted expected LOS were calculated for each patient
      as well. RESULTS: Significant variability in mean total LOS (7.6 to 12.7 days),
      mean acute LOS (7.1 to 10.3 days), and death rates (4.3 to 12.0%) was noted among
      the centers. Minimal variation in mean expected LOS (5.2 to 6.1 days) and mean
      severity score (2.8 to 3.3) was observed. Mean total LOS (r = 0.14, p = 0.61) and
      acute LOS (r = 0.11, p = 0.69) were not related significantly to death rate for
      the 15 centers. When the hospitals were separated into tertiles based on rank
      order of total LOS and acute LOS, no differences among the subgroups were noted
      in the number of cases per hospital, deaths per hospital, death rates, expected
      LOS, and severity scores, Interhospital variation in total LOS was partially
      explained by the care of patients who did not require acute hospitalization.
      CONCLUSIONS: Significant interhospital variation exists in LOS and death rates
      for patients admitted with CHF; these two measures are not related to each
      another. This variability in outcome cannot be explained by severity of illness
      case-mix alone; significant variation in the processes and effectiveness of
      patient care may exist.

PMID- 9176686
TI  - The dilemmas of parents of adolescents and young adults with congenital heart
      disease.
AB  - OBJECTIVE: To provide a better understanding of parents' experiences as their
      children with congenital heart disease mature through adolescence and young
      adulthood. DESIGN: A qualitative pilot study. SETTING: The physician practices of
      the pediatric cardiology service of a large university medical center. SUBJECTS:
      Eight parents of adolescents and young adults with congenital heart disease.
      INTERVENTION: Each parent was separately interviewed with use of a semistructured
      interview guide. RESULTS: Our study has identified seven themes--the dilemmas of
      normality, disclosure dilemmas, the challenge of uncertainty, illness management
      dilemmas and strategies, social integration versus social isolation, the impact
      of illness on the family, and coping--with which parents have struggled through
      out their adolescent's and young adult's life. It was not possible to determine
      whether the experiences described by these parents are unique. CONCLUSIONS:
      Parents experience distress, as outlined in the seven themes. They need
      assistance to determine what is "normal" for their child and how to monitor their
      child's health and safety. Further research is needed to develop specific
      interventions.

PMID- 9176687
TI  - A study of unplanned readmissions to a coronary care unit.
AB  - OBJECTIVE: To determine the cause and frequency of unplanned readmissions to a
      coronary care unit (CCU) after initial transfer to a general cardiac unit, but
      before hospital discharge. DESIGN: Analysis of 1776 admissions to a CCU during a
      16-month period. SETTING: The CCU of a major teaching hospital in South
      Australia. PARTICIPANTS: All patients admitted to the CCU during the 16-month
      period. OUTCOME MEASURES: CCU readmissions before hospital discharge were
      categorized as either "planned" or "unplanned." The latter were investigated for
      determination of casualty and variations in patient characteristics (including
      age, sex, initial diagnosis, pharmacotherapy, and duration of stay in the CCU).
      RESULTS: Of the 1776 CCU admissions examined, 44 (2.5% of total) were unplanned
      readmissions before hospital discharge. Most of these (39 of 44) were related to
      "reactivation" of acute myocardial ischemia. Patients whose initial diagnosis was
      acute myocardial infarction or unstable angina pectoris were more likely to
      require a further unplanned CCU admission (p < 0.05); those with unstable angina
      pectoris had a second stay in CCU significantly longer than their first (p <
      0.05). Six patients were readmitted within 6 hours of cessation of a heparin
      infusion (4 of the 6 without aspirin administration), and 11 patients had not
      received antiplatelet therapy after their initial CCU stay. Overall, a
      disproportionate number of men were readmitted to CCU (p < 0.05). CONCLUSIONS: In
      the current study, unplanned readmissions to the CCU: (1) were relatively
      infrequent, (2) were more protracted than initial stays in CCU, (3) may have been
      prevented in 15 of the 44 cases with more appropriate pharmacotherapy, and (4)
      involved a disproportionate number of male patients.

PMID- 9176688
TI  - Arterial waveforms: monitoring changes in configuration.
AB  - Arterial waveform configuration is an underused monitoring tool in the intensive
      care setting. Characteristic changes in configuration occur throughout the
      illness-wellness continuum for a number of disease processes. The cases presented
      illustrate the opportunity for preliminary diagnosis and early intervention.

PMID- 9176689
TI  - Dysphagia in the patient with a tracheostomy: six cases of inappropriate cuff
      deflation or removal.
AB  - Patients with tracheostomy tubes have altered motor and sensory functions that
      may decrease their swallowing efficiency. Failure to recognize disorders in
      deglutition may result in dangerous complications including aspiration and death.
      Assessment of dysphagia is especially important in the patient transferred from
      the intensive care unit to the ward--where resources are less abundant. We
      present six cases in which cuff deflation or change of tracheostomy tube were
      undertaken without documented swallowing assessment. In these cases each patient
      was found to be aspirating and required the cuff to be reinflated, or a cuffed
      tube to be reinstated when assessed by the multidisciplinary team. Dysphagia
      management in the patient with a tracheostomy should be approached from a
      multidisciplinary point of view so that appropriate decisions can be made
      regarding changes in management and the decannulation process.

PMID- 9176690
TI  - Nursing assessment and management of pain in critically ill children.
AB  - OBJECTIVES: To describe how nurses assess and manage pain in critically ill
      children. DESIGN: Descriptive, comparative research design, with use of the
      Indicators of Pain in Critically Ill Children assessment tool. SETTING: Twelve
      bed pediatric intensive care unit in a metropolitan general hospital with a level
      II pediatric trauma center. PARTICIPANTS: Twenty-four pediatric intensive care
      unit nurses who conducted 112 assessments of 25 critically ill children. RESULTS:
      Pain indicators selected most frequently by nurses included cardiovascular and
      respiratory changes (increased heart rate, respiratory rate, and blood pressure),
      followed by behavioral indicators (irritable/fussy, verbalizing pain, crying),
      and neuromuscular responses (tenseness/rigidity, squirming, drawing up legs). The
      average number of pain indicators selected during each medication event was 5.3.
      More indicators were selected for trauma, surgery, and younger patients; fewer
      indicators were selected for patients receiving ventilation treatment.
      CONCLUSION: Pain assessment of critically ill children includes unique
      indicators, as compared to less sick children, and must take into account the
      child's decreased ability to communicate pain.

PMID- 9176691
TI  - The effects of psyllium hydrophilic mucilloid on diarrhea in enterally fed
      patients.
AB  - OBJECTIVE: To investigate the efficacy of psyllium hydrophilic mucilloid (PHM)
      for prevention of diarrhea and to compare methods of PHM delivery. DESIGN:
      Experimental. SETTING: University-affiliated Department of Veterans Affairs
      Medical Center. SUBJECTS: Sixty patients from medical-surgical and intensive care
      units who received newly initiated enteral feeding via feeding tube. OUTCOME
      MEASURES: Diarrhea, stool frequency and consistency, and feeding tube
      obstruction. INTERVENTION: Receipt of PHM (7 gm, twice-daily) added to continuous
      feeding or given as a bolus with intermittent feeding, or receipt of No PHM for 7
      days after initiation of enteral feeding. RESULTS: Fifteen subjects (25%)
      developed diarrhea (defined as 3 or more liquid stools per day, or 2 or more
      liquid stools on successive days). There were no significant differences in
      incidence of diarrhea or percentage of days of diarrhea between subjects who did
      and did not receive PHM. However, subjects who received PHM in their continuous
      feedings had a significantly higher number of gelatinous stools, and the combined
      PHM groups had a significantly lower number of liquid stools and a higher number
      of normal stools than did subjects who did not receive PHM. For the combined PHM
      groups, there was a 12% incidence of small-bore feeding tube occlusion--requiring
      replacement. CONCLUSIONS: Further study with a larger sample is necessary to
      evaluate trends found in this pilot study and to determine PHM efficacy for
      prevention of diarrhea. PHM administration may result in small-bore feeding tube
      obstruction, and thus requires adequate dilution and close monitoring.

PMID- 9176692
TI  - The use of decision analysis to examine ethical decision making by critical care
      nurses.
AB  - OBJECTIVE: To examine the extent to which critical care staff nurses make ethical
      decisions that coincide with those recommended by a decision analytic model.
      DESIGN: Nonexperimental, ex post facto. SETTING: Midwestern university-affiliated
      500 bed tertiary care medical center. SUBJECTS: One hundred critical care staff
      nurses randomly selected from seven critical care units. Complete responses were
      obtained from 82 nurses (for a final response rate of 82%). MEASURES: The
      dependent variable--consistent decision making--was measured as staff nurses'
      abilities to make ethical decisions that coincided with those prescribed by the
      decision model. Subjects completed two instruments, the Ethical Decision Analytic
      Model, a computer-administered instrument designed to measure staff nurses'
      abilities to make consistent decisions about a chemically-impaired colleague; and
      a Background Inventory. RESULTS: The results indicate marked consensus among
      nurses when informal methods were used. However, there was little consistency
      between the nurses' informal decisions and those recommended by the decision
      analytic model. Although 50% (n = 41) of all nurses chose a course of action that
      coincided with the model's least optimal alternative, few nurses agreed with the
      model as to the most optimal course of action. The findings also suggest that
      consistency was unrelated (p > 0.05) to the nurses' educational background or
      years of clinical experience; that most subjects reported receiving little or no
      education in decision making during their basic nursing education programs; but
      that exposure to decision-making strategies was related to years of nursing
      experience (p < 0.05). CONCLUSIONS: The findings differ from related studies that
      have found a moderate degree of consistency between nurses and decision analytic
      models for strictly clinical decision tasks, especially when those tasks were
      less complex. However, the findings partially coincide with other findings that
      decision analysis may not be particularly well-suited to the critical care
      environment. Additional research is needed to determine whether critical care
      nurses use the same decision-making methods as do other nurses; and to clarify
      the effects of decision task (clinical versus ethical) on nurses' decision
      making. It should not be assumed that methods used to study nurses' clinical
      decision making are applicable for all nurses or all types of decisions,
      including ethical decisions.

PMID- 9176693
TI  - Bacillus species pseudomeningitis.
AB  - Bacillus species are aerobic gram-positive bacilli that are usually found in
      nature in the soil and dust. Except for B. anthracis, Bacillus species are
      organisms of low virulence, and only rarely cause infections in immunocompromised
      hosts. The recovery of Bacillus species from body fluids in healthy patients
      would suggest a Bacillus species pseudoinfection. Bacillus species has been
      associated with both pseudobacteremia and least commonly, pseudomeningitis. The
      Bacillus organisms usually contaminate liquid culture media, which have been
      implicated in Bacillus pseudoinfections of the blood and cerebrospinal fluid. We
      report a case of Bacillus pseudomeningitis in a normal host. To our knowledge,
      this is the third case of Bacillus pseudomeningitis reported in the literature.

PMID- 9176694
TI  - Adult respiratory distress syndrome: a disorder in need of improved outcome.

PMID- 9176695
TI  - Chance encounters and organized rendezvous.

PMID- 9176696
TI  - Cords, channels, corridors and conduits: critical architectural elements
      facilitating cell interactions in the lymph node cortex.
AB  - The lymph node cortex is a critical site for encounter between recirculating T
      cells and their specific antigens. Due to its extreme plasticity, little is
      understood of the underlying functional unit of the lymph node cortex, the
      paracortical cord. The idealized paracortical cord (approximately 100 microns by
      1000 microns) stretches from a medullary cord to the base of a B-cell follicle.
      In cross-section, a cord can be visualized as a set of nested cylinders
      consisting of spaces bounded by cells. The spaces are: i) the lumen of the high
      endothelial venule (HEV), ii) perivenular channels-narrow potential spaces (0.1
      micron) tightly encircling the HEV, iii) corridors-broad spaces (10-15 microns)
      constituting the majority of the parenchyma, and iv) the cortical sinus. In
      addition to these spaces for cell traffic, the conduit (fifth space) is a special
      delivery system for the transit of soluble factors to the HEV and emigrating
      lymphocytes. The cellular barriers between these spaces are high endothelium,
      fibroblastic reticular cells, or sinus-lining cells. This review describes the
      spaces of the paracortical cord and their cellular boundaries, outlines the
      movement of cells and fluids through these spaces, and discusses how this anatomy
      affects the efficiency of surveillance by T cells.

PMID- 9176697
TI  - Dendritic cells in the T-cell areas of lymphoid organs.
AB  - Substantial numbers of dendritic cells (DCs) are found in the T-cell areas of
      peripheral lymphoid organs such as the spleen, lymph node and Peyer's patch. By
      electron microscopy these DCs (also called interdigitating cells) form a network
      through which T-cells continually recirculate. The cytological features of DCs in
      the T-cell areas, as well as a number of markers detected with monoclonal
      antibodies, are similar to mature DCs that develop from other sites such as skin
      and bone marrow. Some markers that are expressed in abundance are: MHC II and the
      associated invariant chain, accessory molecules such as CD40 and CD86, a
      multilectin receptor for antigen presentation called DEC-205, the integrin CD11c,
      several antigens within the endocytic system that are detected by monoclonal
      antibodies but are as yet uncharacterized at the molecular level, and, in the
      human system, molecules termed S100b, CD83 and p55. DCs in the periphery can pick
      up antigens and migrate to the T-cell areas to initiate immunity. However, there
      are new observations that DCs within the T-cell areas also express high levels of
      self-antigens and functional fas-ligand capable of inducing CD4+ T-cell death. We
      speculate that there are at least 2 sets of DCs in the T-cell areas, a migratory
      myeloid pathway that brings in antigens from the periphery and induces immunity,
      and a more resident lymphoid pathway that presents self-antigens and maintains
      tolerance.

PMID- 9176698
TI  - Follicular dendritic cells and presentation of antigen and costimulatory signals
      to B cells.
AB  - This review focuses on how immunogens trapped by FDC in the form of Ag-Ab
      complexes productively signal B cells. In vitro. Ag-Ab complexes are poorly
      immunogenic but in vivo immune complexes elicit potent recall responses. FDC trap
      Ag-Ab complexes and make immune complex coated bodies or "iccosomes". B cells
      endocytose iccosomes, the Ag is processed, and T-cell help is elicited. In vitro,
      addition of FDC bearing appropriate Ag-Ab complex to memory T and B cells provoke
      potent recall responses (IgG and IgE). FDC also provide nonspecific costimulatory
      signals which augment B-cell proliferation and Ab production. B cell-FDC contact
      is important and interference with ICAM-1-LFA-1 interactions reduces FDC-mediated
      costimulation. Preliminary data suggest that a costimulatory signal may be
      delivered via CR2L on FDC binding CR2 on B cells. FDC can also stimulate B cells
      to become chemotactically active and can protect lymphocytes from apoptosis. FDC
      also appear to be rich in thiol groups and may replace reducing compounds such as
      2 mercaptoethanol in cultures. In short, FDC-Ag specifically signals B cells
      through BCR, and FDC provide B cells with iccosomal-Ag necessary for processing
      to elicit T-cell help. In addition, FDC provide nonspecific signals that are
      important to promote B-cell proliferation, maintain viability, and induce
      chemotactic responsiveness.

PMID- 9176699
TI  - The changing preference of T and B cells for partners as T-dependent antibody
      responses develop.
AB  - Recirculating virgin CD4+ T cells spend their life migrating between the T zones
      of secondary lymphoid tissues where they screen the surface of interdigitating
      dendritic cells. T-cell priming starts when processed peptides or superantigen
      associated with class II MHC molecules are recognised. Those primed T cells that
      remain within the lymphoid tissue move to the outer T zone, where they interact
      with B cells that have taken up and processed antigen. Cognate interaction
      between these cells initiates immunoglobulin (Ig) class switch-recombination and
      proliferation of both B and T cells; much of this growth occurs outside the T
      zones B cells migrate to follicles, where they form germinal centres, and to
      extrafollicular sites of B-cell growth, where they differentiate into mainly
      short-lived plasma cells. T cells do not move to the extrafollicular foci, but to
      the follicles; there they proliferate and are subsequently involved in the
      selection of B cells that have mutated their Ig variable-region genes. During
      primary antibody responses T-cell proliferation in follicles produces many times
      the peak number of T cells found in that site: a substantial proportion of the
      CD4+ memory T-cell pool may originate from growth in follicles.

PMID- 9176700
TI  - Use of adoptive transfer of T-cell-antigen-receptor-transgenic T cell for the
      study of T-cell activation in vivo.
AB  - Adoptive transfer of TCR-transgenic T cells uniformly expressing an identifiable
      TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior
      of antigen-specific T cells. We have used this system to show that naive T cells
      are initially activated within the T-cell zones of secondary lymphoid tissue to
      proliferate in a B7-dependent manner. If adjuvants or inflammatory cytokines are
      present during this period, enhanced numbers of T cells accumulate, migrate into
      B-cell-rich follicles, and acquire the capacity to produce IFN-gamma and help B
      cells produce IgG2a. If inflammation is absent, most of the initially activated
      antigen-specific T cells disappear without entering the follicles, and the
      survivors are poor producers of IL-2 and IFN-gamma. Our results indicate that
      inflammatory mediators play a key role in regulating the anatomic location,
      clonal expansion, survival and lymphokine production potential of antigen
      stimulated T cells in vivo.

PMID- 9176701
TI  - Factors controlling the turnover of T memory cells.
AB  - Most of the T cells participating in the primary immune response are rapidly
      eliminated, but small numbers of these cells survive and differentiate into long
      lived memory cells. Information on the life history of memory cells can be
      obtained by studying the component of memory-phenotype T cells found in normal
      animals; these cells are presumed to represent memory cells specific for various
      environmental antigens. For CD8+ cells, in vivo exposure to viruses and certain
      other infectious agents causes a large proportion of memory-phenotype (CD44hi)
      cells to enter the cell cycle. In this situation, stimulation of CD44hi CD8+
      cells does not seem to require T-cell receptor ligation and appears to reflect
      release of various cytokines, especially type I interferon. The capacity of
      infectious agents to induce non-antigen-specific stimulation of T cells may play
      a role in boosting the survival of memory cells and perhaps also in providing an
      adjuvant function during the primary response.

PMID- 9176702
TI  - Signaling thresholds and interclonal competition in preimmune B-cell selection.
AB  - The need to eliminate autoreactive B cells must be checked against the need for a
      diverse B-cell repertoire. Protein tyrosine phosphatases SHP1 and CD45 act
      antagonistically within B cells to set the threshold level of antigen-receptor
      engagement required for B-cell elimination. The fate of B cells binding weak
      autoantigens is also regulated by interclonal competition. In the presence of a
      normal diverse repertoire of competitor B cells, the autoantigen-binding cells
      are excluded from follicles in spleen and lymph nodes and undergo rapid cell
      death. In the absence of interclonal competition, the autoreactive cells enter
      the follicular microenvironment and survive. A model in which B cells compete for
      access to limiting follicular niches in order to survive is discussed.

PMID- 9176703
TI  - Unique site of IgG2a and rheumatoid factor production in MRL/lpr mice.
AB  - MRL/lpr (Fas-deficient) mice develop an autoimmune syndrome associated with
      excessive production of autoantibodies. A significant portion of these
      autoantibodies are IgG2a molecules specific for many of the autoantigens
      recognized by the sera of patients with systemic lupus erythematosus. In
      addition, MRL/lpr mice make exceedingly high titers of IgG or IgA rheumatoid
      factors (RF) specific for autologous IgG2a. The microenvironment of the IgG2a
      producing B cells as well as the prototypic RF autoantibodies was determined by a
      combination of immunohistochemical and in situ hybridization techniques. In
      contrast to the antibody-producing cells present in mice responding to
      conventional foreign antigens, both IgG2a+ and RF+ B cells were found to be
      densely clustered in the T-cell-rich inner periarteriolar lymphatic sheath of the
      spleen. These results suggest that conventional antibody and autoantibody
      production in MRL/lpr mice may be mechanistically distinct processes.

PMID- 9176704
TI  - The physiology of murine germinal center reactions.
AB  - Germinal center responses are the mechanism that the immune system uses normally
      to generate high affinity antigen-specific B-cell receptors and secreted
      immunoglobulins. Genetically altered mice have provided powerful tools for
      dissecting the physiology of these germinal center responses. In this review, we
      have attempted to summarize information from various sources and interpret the
      new observations based on what was previously known. A section is included to
      review the basic anatomy of the relevant structures in lymph node and spleen. A
      summary of the mutant mice producing a phenotype where germinal center responses
      are altered is also furnished. This review is aimed at providing useful
      information to those working in this field as well as those wishing to understand
      more about in vivo immunology.

PMID- 9176705
TI  - Lymphotoxin-alpha-deficient and TNF receptor-I-deficient mice define
      developmental and functional characteristics of germinal centers.
AB  - Mice deficient in LT alpha (LT alpha-/-) lack lymph nodes and Peyer's patches.
      This action of LT alpha in lymph node organogenesis appears to be mediated by the
      membrane form of LT using a mechanism independent of TNF receptor I (TNFR-I) or
      II (TNFR-II). In contrast, normal Peyer's patch development appears to require
      both LT alpha and TNFR-I, with TNFR-I-/- mice showing hypoplastic Peyer's patch
      structures. LT alpha-/- mice also fail to support the normal segregation of T
      cell and B-cell zones within the splenic white pulp. Again, this occurs via a
      mechanism independent of TNFR-I or TNFR-II. Additionally, follicular dendritic
      cell (FDC) clusters or germinal centers fail to develop in the spleen of LT alpha
      /- animals. Mice deficient in either TNF alpha or TNFR-I also fail to develop
      splenic FDC clusters and germinal centers, indicating that signaling by both LT
      alpha and TNF alpha is required for development of these specialized lymphoid
      tissue structures. Finally, the splenic white pulp areas in LT alpha-/- mice lack
      the marginal zone of monoclonal antibody MOMA-1-staining metallophilic
      macrophages, whereas TNFR-I-deficient mice have preserved MOMA-1 staining. Thus,
      certain actions of LT alpha to regulate spleen white pulp architecture are
      mediated by receptors other than TNFR-I, most likely by the LT beta R or a
      closely related receptor. We tested whether germinal centers are essential for
      maturation of T-cell-dependent antibody responses. When LT alpha-/- mice were
      immunized with low doses of NP-ovalbumin (NP-OVA) adsorbed to alum, there was
      dramatically impaired production of high affinity anti NP IgG; however, after
      immunization with high doses of NP-OVA adsorbed to alum, LT alpha-/- mice mounted
      a high affinity NP-specific serum IgG response similar to wild-type mice, all in
      the absence of germinal centers or clustered FDC. Thus, although germinal centers
      enhance the processes required for maturation of the humoral immune response, the
      mechanisms responsible for affinity maturation are not absolutely dependent on
      the presence of germinal centers.

PMID- 9176706
TI  - The anatomical basis of intestinal immunity.
AB  - The lymphoid tissues associated with the intestine are exposed continuously to
      antigen and are the largest part of the immune system. Many lymphocytes are found
      in organised tissues such as the Peyer's patches and mesenteric lymph nodes, as
      well as scattered throughout the lamina propria and epithelium of the mucosa
      itself. These lymphocyte populations have several unusual characteristics and the
      intestinal immune system is functionally and anatomically distinct from other,
      peripheral compartments of the immune system. This review explores the anatomical
      and molecular basis of these differences, with particular emphasis on the factors
      which determine how the intestinal lymphoid tissues discriminate between harmful
      pathogens and antigens which are beneficial, such as food proteins or commensal
      bacteria. These latter antigens normally provoke immunological tolerance, and
      inappropriate responses to them are responsible for immunopathologies such as
      food hypersensitivity and inflammatory bowel disease. We describe how
      interactions between local immune cells, epithelial tissues and antigen
      presenting cells may be critical for the induction of tolerance and the
      expression of active mucosal immunity. In addition, the possibility that the
      intestine may act as an extrathymic site for T-cell differentiation is discussed.
      Finally, we propose that, under physiological conditions, immune responses to
      food antigens and commensal bacteria are prevented by common regulatory
      mechanisms, in which transforming growth factor beta plays a critical role.

PMID- 9176707
TI  - A vision of cell death: insights into immune privilege.
AB  - Immune privilege is a term applied to several organs that have a unique
      relationship with the immune response. These sites prohibit the spread of
      inflammation since even minor episodes can threaten organ integrity and function.
      The most prominent examples of these are the eye, brain and reproductive organs
      where immune responses either do not proceed, or proceed in a manner different
      from other areas. Once thought to be a passive process relying on physical
      barriers, immune privilege can now be viewed as an active process that utilizes
      multiple mechanisms to maintain organ function. Recently there has been a renewed
      interest in immune privilege when it was shown that two privileged sites (the eye
      and testes) constitutively express FasL, which functions by killing lymphoid
      cells that invade these areas. Here we will examine the role of FasL in immune
      privilege and discuss how this molecule interacts with other elements of the
      inflammatory response to maintain organ integrity in the face of potentially
      damaging immune reactions.

PMID- 9176708
TI  - Follicular dendritic cells (FDC) in retroviral infection: host/pathogen
      perspectives.
AB  - Follicular dendritic cells (FDC) are found in the follicles of virtually all
      secondary lymphoid tissues. In health, these cells trap and retain antigens (Ag)
      in the form of immune complexes and preserve them for months in their native
      conformation. FDC thus serve as a long-term repository of extracellular Ag
      important for induction and maintenance of memory responses. In retroviral
      infection, FDC trap and retain large numbers of retroviral particles with
      profound effects on FDC. FDC-trapped retrovirus induces follicular hyperplasia,
      and conventional Ag trapped prior to infection are lost and new Ag cannot be
      trapped. Concomitantly, antibody-forming cells (AFC) specific for Ag lost from
      FDC decrease followed by loss of specific serum antibody (Ab). Eventually, FDC
      die and follicular lysis occurs. From the pathogen perspective, binding to FDC is
      remarkably beneficial, bringing together virus and activated target cells that
      are highly susceptible to infection. Furthermore, FDC permit HIV to infect
      surrounding cells even in the presence of a vast excess of neutralizing Ab.
      Preliminary data suggest that FDC maintain virus infectivity-even when the virus
      cannot replicate. Thus retrovirus infection monopolizes FDC networks, thereby
      transforming the FDC Ag repository into a highly infectious retroviral reservoir.

PMID- 9176709
TI  - Antigen localisation regulates immune responses in a dose- and time-dependent
      fashion: a geographical view of immune reactivity.
AB  - This review summarises experimental evidence to illustrate that induction of
      immune reactivity depends upon antigen reaching and being available in lymphoid
      organs in a dose- and time-dependent manner. If antigen reaches lymph organs in a
      localised staggered manner and with a concentration gradient, a response is
      induced in the draining lymph node. Antigen-presenting cells are of critical
      importance to transport antigen from the periphery to local organised lymphoid
      tissue. If antigen is all over the lymphoid system, then it deletes all specific
      cells in the thymus or induces them within a few days; because of their limited
      life-span they then die off, leaving the repertoire depleted of this specificity.
      If antigen does not reach lymphoid organs it is ignored by immune cells. Once a
      response is induced, activated but not resting T cells will reach antigen outside
      lymphoid organs, whereas activated B cells differentiate into plasma cells in an
      inducing environment, mostly in lymphoid tissue including bone marrow, but also
      in chronic lymphoid-like infiltrations in peripheral organs. In immunopathology
      (when the infectious agent is known) or in autoimmunity (when the triggering
      infectious agent is not known or not recognised) lymphoid tissue may become
      organised close to the antigen (e.g. in organ-specific autoimmune diseases) and
      may thereby maintain an autoantigen-driven disease-causing immune response for a
      long time. The notion that native T cells get induced or silenced in the
      periphery may be questioned because induction can only occur in lymphoid organs
      providing anatomical structures where critical cell-cell interactions are
      properly guided and where, therefore, cells are likely to meet sufficiently
      frequently and in a critical milieu. Since overall immune reactivity critically
      depends upon the localisation of antigens in a dose- and time-dependent manner,
      it seems more likely-but this remains to be shown-that activated T cells may get
      exhausted in non-lymphoid peripheral tissues, whereas they are usually maintained
      in lymphoid organs. The critical role of antigen in regulating immune responses
      also has relevance for our understanding of immunological defence against
      epithelial and mesenchymal tumours, against many infectious diseases and for
      understanding autoimmunity and immunological memory. Collectively the data
      indicate that antigen, dependent upon localisation, dose and time, seems to be
      the simplest regulator of immune responses.

PMID- 9176710
TI  - Production and characterization of monoclonal antibodies directed against the
      laminin receptor precursor.
AB  - The 67-kDa laminin receptor (67LR) is an important tumor marker whose molecular
      structure has not yet been fully elucidated. To shed new light on this molecule,
      we raised a series of eight new monoclonal antibodies, designated MPLR1 to 8,
      directed against the 37-kDa recombinant laminin receptor precursor (37LRP). Cross
      competition experiments demonstrated that the epitopes recognized by MPLR2, 4 and
      5 partially overlap, since MPLR4 and 5 compete with labelled MPLR2 for the
      binding to recombinant 37LRP. These three antibodies belong to the IgG1 class,
      whereas the other ones are all IgM. Presumably due to the fact that they are
      directed against partially unfolded antigenic determinants expressed on the
      recombinant protein, MPLRs did not recognize the native protein. Indeed, they
      showed no reactivity at the membrane level in cytofluorimetric analysis and they
      did not work in immunoprecipitation experiments. In contrast, these reagents are
      valuable tools in immunoblotting, since they clearly identify a 67-kDa protein
      (the mature laminin receptor) in addition to the 37-kDa precursor form. MPLRs are
      thus a new powerful tool which could help in the characterization of the still
      enigmatic 67LR molecule.

PMID- 9176711
TI  - A sensitive and robust assay for urokinase and tissue-type plasminogen activators
      (uPA and tPA) and their inhibitor type I (PAI-1) in breast tumor cytosols.
AB  - uPA and PAI-1 are becoming established as amongst the most effective markers of
      poor prognosis for patients with node-negative breast cancer; tPA is an index of
      longer survival. This paper describes a sensitive ELISA for the measurement of
      uPA, tPA and PAI-1 in breast cancer cytosols. The structure of the assay involves
      coating Ab (sheep alpha-Chicken IgY), catching Ab (chicken alpha-analyte),
      tagging Ab (rabbit alpha-analyte) and detecting Ab (goat alpha-rabbit IgG)
      labelled with HRP. The assay has a high degree of accuracy and specificity.
      Comparison with the American Diagnostic kits shows the results' equivalence for
      PAI-1 and tPA. For uPA the results of the assay were twice as high. The assay is
      sensitive and relatively inexpensive. It is the first published assay to yield
      strictly comparative values for uPA, tPA and PAI-1 in tissue extracts and is
      readily subject to external quality control.

PMID- 9176712
TI  - How to overcome the disturbing effects of human anti-mouse antibodies (HAMA) on
      in vitro assays.
AB  - The development of human anti-mouse antibodies (HAMA) is a common immune response
      in patients with ovarian carcinoma after repeated injections of murine anti-CA
      125 monoclonal antibodies for immunoscintigraphy. As a tumor marker with
      significant diagnostic value CA 125 is routinely measured in the follow-up of
      tumor patients by immunoradiometric assays (IRMA) based on murine anti-CA 125
      monoclonal antibodies. HAMA may cause false-positive findings in a CA 125-IRMA.
      In this report our group demonstrates a simple way of eliminating HAMA by protein
      A/G affinity chromatography allowing the reliable detection of the tumor marker
      CA 125 in the serum of patients with ovarian carcinoma.

PMID- 9176713
TI  - Evaluation of serum carcinoembryonic antigen monitoring in the follow-up of
      colorectal cancer patients with metastatic lymph nodes and a normal preoperative
      serum level.
AB  - The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up
      of colorectal cancer patients with metastatic lymph nodes and normal (< or = 5
      ng/ml) preoperative CEA levels, was examined in this study. Thirty-eight patients
      were studied and compared with 22 patients with elevated CEA levels. The overall
      sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was
      strongly influenced by the site of recurrence. CEA monitoring showed the best
      results in patients who developed hepatic metastases (sensitivity 60%,
      specificity 94%, positive predictive value 60%, and negative predictive value
      94%), and was ineffective for the detection of locoregional or pulmonary
      metastases. The results indicate that elevation of CEA in the postoperative
      course of these patients is an indicator of the presence of hepatic metastases.
      Postoperative CEA monitoring should not be omitted in Dukes C patients with
      normal preoperative levels, and is more reliable for the detection of liver
      metastases.

PMID- 9176714
TI  - Immunoassay of neuron-specific enolase (NSE) and serum fragments of cytokeratin
      19 (CYFRA 21.1) as tumor markers in small cell lung cancer: clinical evaluation
      and biological hypothesis.
AB  - NSE is a biochemical marker for small cell lung cancer (SCLC) diagnosis and
      management. CYFRA 21.1 is a newly developed immunoassay to detect the serum
      fragments of cytokeratin 19 which are also expressed in SCLC with or without
      neurofilaments. The aim of this study was to evaluate the diagnostic performance
      and prognostic role of the two markers in SCLC and their contribution to
      chemotherapy monitoring and patient follow-up. We studied 62 patients with
      pathologically proven SCLC: 28 with limited disease (LD) and 34 with extensive
      disease (ED), and 100 patients with non-malignant pulmonary disease.
      Immunoradiometric assays (IRMA) were employed to test NSE and CYFRA 21.1 in
      patients and control subjects. For each patient subset results were expressed as
      median and interquartile distribution range. NSE and CYFRA 21.1 sensitivity was
      0.52 (33/62) and 0.56 (35/62), respectively. In the group of patients with LD,
      NSE and CYFRA 21.1 sensitivity was 0.42 (12/28) and 0.54 (15/28) and in patients
      with ED, NSE and CYFRA 21.1 were positive in 0.62 (21/34) and 0.59 (20/34) of
      cases, respectively. Combining the two markers, a sensitivity of 0.78 (22/28) in
      LD, 0.82 (28/34) in ED and a global sensitivity of 0.80 (50/62) was obtained.
      Only NSE was significantly linked to the extension of disease (Mann-Whitney U
      test p = 0.002) while CYFRA 21.1 did not correlate. The analysis of survival and
      the evaluation of the two markers at diagnosis showed CYFRA 21.1 to be strongly
      linked to the patients' outcome, independently of both clinical prognostic
      factors and NSE levels (log rank and Cox's model). The markers' performance
      during chemotherapy was tested in a group of 33 patients with at least one marker
      above cut-off. NSE can be considered a reliable marker of tumor mass
      modifications under chemotherapy, while CYFRA 21.1 expression seems to be
      relatively independent of tumor volume modifications. An applicable model of
      biomarkers in SCLC could be the concurrent assay of NSE and CYFRA 21.1 in pre
      therapeutic assessment and therapy planning. CYFRA 21.1 does not play an
      important role during therapy monitoring and follow-up; in these phases NSE alone
      may be employed.

PMID- 9176715
TI  - Tissue polypeptide-specific antigen (TPS) immunoassay in the diagnosis and
      clinical staging of prostatic carcinoma. Comparison with prostate-specific
      antigen (PSA).
AB  - This experimental study investigated the potential role of Tissue Polypeptide
      Specific Antigen (TPS) in comparison with Prostate-Specific Antigen (PSA) in the
      diagnosis and the clinical and pathological staging of prostate cancer. Serum TPS
      and PSA levels were determined in 128 patients (pts) with benign prostatic
      hypertrophy (BPH; Group 1) and in 92 pts with prostate cancer (Group 2). TPS was
      also measured in a control group of 100 healthy subjects. Normal cutoff values of
      85 U/l for TPS and 4 ng/ml for PSA were determined on the basis of ROC curve
      analysis. The sensitivity, specificity and accuracy in the diagnosis of prostate
      cancer were 49%, 95% and 76% for TPS, and 84%, 90% and 87% for PSA. The
      combination of the two markers provided a higher accuracy (88%), improving the
      sensitivity of PSA, since 47% of patients with normal PSA had pathological levels
      of TPS. TPS showed an increase in sensitivity from low to higher stages of
      disease and, in patients with skeletal involvement, from small to larger numbers
      of bone metastases (Kruskal Wallis p < 0.0001). Nevertheless, TPS serum levels
      are not useful in the clinical staging of prostate cancer as they have a poorer
      performance than PSA. TPS was ineffective (ROC curve area = 0.68) in predicting
      extraprostatic disease and demonstrated a reduced ability (area = 0.78) to
      identify skeletal involvement. Moreover, the combination of the two markers did
      not significantly improve the performance of PSA alone. The serum concentration
      of TPS in patients with localized tumors was not related to the degree of tumor
      cell differentiation evaluated by the Gleason score. CONCLUSION: Our preliminary
      experience suggests that TPS in association with PSA may be useful at the time of
      diagnosis of prostate cancer. However, these preliminary data have to be
      confirmed by larger clinical trials and the role of this association in the
      clinical setting needs to be analyzed with an adequate evaluation of the cost
      effectiveness ratio.

PMID- 9176716
TI  - Evaluation of western blot in routine diagnosis of hepatitis C virus.
AB  - Hepatitis C virus (HCV) is among the major causes of parenterally transmitted
      hepatitis. Detection of infected persons would greatly diminish transmission
      rates and is therefore a significant parameter for prevention. Current assays are
      not able to resolve all cases and sometimes the results are controversial. The
      present study outlines problems that arise during routine testing. Two ELISA
      tests and three confirmatory tests were used and Polymerase Chain Reaction (PCR)
      data were available for some of the samples. The results of this study show that
      only 77.4% of samples positive for both ELISAs were confirmed as being positive.
      Controversial ELISA results remained controversial, depending on the confirmatory
      test used. PCR results, though not complete, point to the major problem of
      Western blot (WB) negative sera that prove positive for the viral genome and have
      to be excluded from screening for blood and organ donation. Since PCR cannot be
      used as a routine screening procedure, improvement of the routine assays is
      needed to minimize ambiguous results.

PMID- 9176717
TI  - Production of a novel monoclonal antibody against MUC4 mucin.

PMID- 9176718
TI  - Pulmonary carcinoembryonic antigen (CEA) production in patients with end-stage
      lung diseases submitted to lung transplantation.

PMID- 9176719
TI  - Effect of basic fibroblast growth factor on angiogenesis and growth of isografted
      bone: quantitative in vitro-in vivo analysis in mice.
AB  - Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage
      matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes
      and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To
      characterize the effect of bFGF on bone formation, whole neonatal murine femora
      were cultured in the presence or absence of bFGF and a neutralizing antibody
      against bFGF. In vitro, femoral elongation was provided by cartilage growth only;
      the calcified diaphyseal zone stained by oxytetracycline did not increase. When
      bFGF was added to the culture medium, longitudinal growth of the proximal and
      distal cartilage was inhibited in a dose-dependent manner (p < 0.05), and the
      number of hypertrophic chondrocytes in the growth plate was reduced. This
      phenomenon was absent in the presence of a neutralizing antibody, which when
      given alone significantly promoted femoral elongation. In contrast, in vivo after
      transplantation into adult mice bearing dorsal skin fold chambers, femora rapidly
      calcified after revascularization. This observation supports the notion that bone
      formation largely depends on angiogenesis-mediated events. To verify this
      hypothesis, angiogenesis and bone formation were quantified using bFGF known to
      be a stimulator of angiogenesis. Calcification of grafted femora was accelerated
      by bFGF given intraperitoneally. The neutralizing antibody slightly suppressed
      angiogenesis and femoral elongation (not statistically significant), whereas
      intravenous injections of both substances did not reveal a significant modulatory
      effect. In vivo the effect of systemically administered bFGF was inhomogeneous,
      but there was a strong correlation between angiogenesis and endochondral
      calcification (p < 0.001). These results suggest that exogenous bFGF modulates
      bone formation in vitro by inhibition of terminal differentiation of chondrocytes
      in the growth plate, and angiogenesis and concomitant in vivo events are pivotal
      in the promotion of rapid bone formation.

PMID- 9176720
TI  - Recombinant human granulocyte colony-stimulating factor reverts vascular
      dysfunction.
AB  - The aim of our study was to investigate the vascular effects of recombinant human
      granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible
      vascular failure. Male anesthetized rats were subjected to the clamping of the
      splanchnic arteries for 45 min. This surgical procedure resulted in an
      irreversible state of shock (splanchnic artery occlusion shock) characterized by
      high mortality rate (0% survival, 120 min following the release of clamps), a
      profound hypotension and vascular dysfunction consisting of a marked
      hyporeactivity to phenylephrine (PE 1 nM-10 microM) of aortic rings.
      Administration of recombinant human granulocyte colony-stimulating factor (20
      micrograms/kg i.v. 5 min after the release of occlusion) increased survival rate
      (90% 4 h after the release of occlusion), blunted the profound hypotension and
      reverted the marked vascular dysfunction. Finally, rh G-CSF inhibited the
      activity of inducible nitric oxide synthase in peritoneal macrophages activated
      with endotoxin. Our data suggest that rh G-CSF may influence vascular function
      when low-flow states occur.

PMID- 9176721
TI  - Semi-invasive laser-Doppler flowmetry technique. New application for recordings
      of hemodynamics in combination with manometry of human small intestine.
AB  - A small-bowel manometry tube was supplied with two single-fiber microprobes,
      which recorded blood flow in the proximal small intestine by the laser-Doppler
      flowmetry (LDF) technique. In all experiments, saline was infused intravenously
      as control during the first migrating motor complex (MMC) cycle, and a drug or
      another saline control given intravenously during the second MMC cycle.
      Recordings were performed during phase 1 of MMC, i.e. when motor pattern showed
      quiescence. Adrenaline increased blood perfusion values by 140% in proximal
      duodenum and 95% in distal duodenum. The alpha 2-adrenoceptor agonist clonidine
      decreased the corresponding values by 34 and 25%, respectively, while
      oxymetazoline decreased perfusion by 33 and 44% at the same levels. The beta
      adrenoceptor agonist isoprenaline increased blood perfusion values by 172% in the
      proximal duodenum and 194% in the distal duodenum, whereas the antagonist
      propranolol decreased the corresponding values by 45 and 52%, respectively. In a
      separate group of subjects, propranolol was given after adrenaline. The increase
      in blood perfusion regularly seen after adrenaline was blocked after propranolol
      administration. In conclusion, our findings validate semi-invasive LDF technique
      for studies of hemodynamics in human small intestine under basal motor conditions
      and in drug-induced blood flow changes.

PMID- 9176722
TI  - Correlation between the uptake of sodium fluorescein in the tissue and xenon-133
      clearance and laser Doppler fluxmetry in measuring changes in skin circulation.
AB  - We have measured the plantar forefoot skin circulation by the uptake of sodium
      fluorescein (fluorescein flowmetry), 133Xe clearance and laser Doppler fluxmetry
      in 24 healthy subjects and correlated measurements under basal conditions and
      after provocation by alcohol intake and application of external heat. To assess
      the change in skin circulation between the initial measurement at rest and the
      second measurement after provocation, the coefficient of correlation (r) of the
      fluorescein flowmetry to the fast slope of the 133Xe elimination curve was 0.46
      (p < 0.05), to the slow slope of the 133Xe elimination curve 0.66 (p < 0.001) and
      to laser Doppler fluxmetry 0.86 (p < 0.001). The coefficient of correlation (r)
      of the fluorescence appearance time to fluorescein flowmetry was 0.65 (p <
      0.001), to the fast slope of the 133Xe elimination curve 0.14 (p = 0.42), to the
      slow slope of the 133Xe elimination curve 0.47 (p < 0.05) and to laser Doppler
      fluxmetry 0.63 (p < 0.001). The uptake of sodium fluorescein as measured by
      fluorescein fluxmetry correlates well with both 133Xe clearance and laser Doppler
      fluxmetry in assessing a change in skin circulation in healthy humans. The
      fluorescence appearance time also correlates to the slow slope of the 133Xe
      elimination curve and to laser Doppler fluxmetry though to a lesser extent.

PMID- 9176723
TI  - Geometry of the capillary net in human hearts.
AB  - The geometry of the coronary capillary bed in human hearts was studied using
      samples obtained during cardiac surgery of children operated for tetralogy of
      Fallot and samples from fresh normal hearts used for valve harvesting. The
      results revealed a similar coronary capillary density and heterogeneity of
      capillary spacing in samples from both groups. A double-staining method was used
      to distinguish between capillary segments close to the feeding arteriole
      (proximal capillaries) and segments distant from the arteriole (distal
      capillaries). In both groups of hearts, capillary segment length was consistently
      shorter on the venular than the arteriolar portion of the capillary. Similarly,
      capillary domain areas were also smaller and the resulting capillary supply unit
      was smaller along venular portions compared to arteriolar regions of the
      capillary bed. This distinctive geometry would provide advantageous geometric
      conditions for tissue oxygen supply.

PMID- 9176724
TI  - Correlation between laser Doppler perfusion monitoring and hematocrit in hamster
      cheek pouch microcirculation.
AB  - The aim of this study was to investigate the relationships between laser Doppler
      perfusion monitoring (LDPM) measurements and different systemic hematocrits in
      microcirculation in terms of changes in oscillatory flow patterns. The hamster
      cheek pouch microvasculature was visualized by a fluorescent microscopy
      technique, and LDPM signals were derived from arterioles and venules under
      control conditions and after isovolemic hemodilution with saline and 6% dextran,
      MW 70,000 to 26.1 +/- 2.1%. Vasomotion, oscillations of microvascular blood flow
      (flow motion) and red blood cell (RBC) velocity were analyzed with Fourier
      transform and autoregressive modeling. LDPM recordings presented a significant
      increase in perfusion units (PU) during hemodilution-184 +/- 15 versus baseline
      137 +/- 11 PU in arterioles and 40.2 +/- 3.5 versus 28.6 +/- 4.3 PU in venules
      that was correlated with a significant increment in arteriolar and venular RBC
      velocity. There was a rise in the frequency [2.9 +/- 0.5 cycles per min (cpm) vs.
      1.8 +/- 0.5 cpm] and spectral power of flow motion in arterioles whereas the
      increase in spectral power was related to a decrease in frequency (12.6 +/- 2.1
      vs. 3.6 +/- 0.7 cpm) in venules. Oscillations in arteriolar and venular RBC
      velocity revealed coincident frequency components with flow motion patterns. The
      present data suggest that the LDPM measurements are more sensitive to velocity
      than hematocrit. Furthermore, hemodilution appears to affect differently
      arteriolar and venular flow motion patterns.

PMID- 9176725
TI  - Modulation of sympathetic constriction by the arteriolar endothelium does not
      involve the cyclooxygenase pathway.
AB  - We have recently shown that the responsiveness of rat intestinal arterioles to
      increased sympathetic nerve activity is modulated by the actions of endothelial
      derived nitric oxide. Because the microvascular endothelium can also produce
      vasodilator prostaglandins, the purpose of this study was to determine if
      endogenous cyclooxygenase products also limit sympathetic arteriolar constriction
      in this vascular bed. Intravital microscopy was used to study the responses of
      small feed arteries, first-order arterioles and second-order arterioles to
      perivascular sympathetic nerve stimulation in the superfused rat small intestine.
      Stimulation at 3, 8 and 16 Hz caused frequency-dependent constrictions of each
      vessel type that are abolished by the alpha-adrenoceptor antagonist phentolamine
      (10(-6) M superfusate concentration). The cyclooxygenase inhibitor meclofenamate
      (3 x 10(-5) M superfusate concentration) completely abolished the dilator
      responses to topically applied arachidonic acid, but had no effect on the
      magnitude or rate of sympathetic constriction in any vessel type. These results
      suggest that endogenous cyclooxygenase activity does not influence sympathetic
      tone in the intestinal microvasculature.

PMID- 9176727
TI  - Distribution of glutamine synthetase in the chick forebrain: implications for
      passive avoidance memory formation.
AB  - The glial enzyme glutamine synthetase (GS) converts glutamate to glutamine; the
      latter is used by neurons for the resynthesis of glutamate and GABA. We have used
      a monoclonal antibody to GS to examine the regional distribution of this enzyme
      in the forebrains of day-old chicks. GS was detected in glia throughout the
      rostral and caudal regions of the forebrain and was particularly intense in the
      hippocampus, area parahippocampus and parts of the hyperstriatal and
      paleostriatal complex, regions widely considered to be involved in memory
      formation. Thus, our data provide an anatomical framework for the conclusion that
      neurons require the support of glia in order to restock their glutamate and/or
      GABA transmitter supplies during memory processing.

PMID- 9176726
TI  - Effect of hepatic nerve stimulation and norepinephrine on the laser Doppler flux
      signal from the surface of the perfused rat liver.
AB  - The effect of hepatic nerve stimulation and norepinephrine (NE) on the laser
      Doppler signal from the surface of the perfused rat liver was tested. The livers
      from male Wistar rats were perfused in situ via the portal vein with Krebs
      Henseleit buffer containing 20% bovine erythrocytes (37 degrees C, pH 7.4) and
      total liver blood flow (TLBF) was by timed collection of effluent. Portal
      vascular resistance (PVR) was calculated from the pressure difference across the
      liver. Linearity of laser Doppler flowmetry (LDF) with TLBF was confirmed in all
      preparations. Stimulation of the hepatic nerves (2 ms, 20 V) was performed at
      frequencies between 0.5 and 20 Hz (n = 11). NE was added to the buffer at
      concentrations between 10(-10) and 10(-6) M (n = 8). A stimulus-dependent rise in
      PVR occurred during hepatic nerve stimulation (basal, 3.11 +/- 0.26 dyn s cm-5)
      and NE administration (basal, 2.62 +/- 0.29 dyn s cm-5), with a maximum effect at
      20 Hz (311 +/- 45%) and 10(-6) M (591 +/- 72%), respectively. Both LDF and TLBF
      fell during nerve stimulation and NE. A linear relationship (r = 0.99; p < 0.001)
      between change in TLBF (%) and LDF flux (%) was found for NE (10(-10) to 10(-6)
      M). During nerve stimulation, the fall in TLBF and LDF flux was linear with the
      logarithm of stimulus frequency and reached a maximum at 10 and 20 Hz,
      respectively. At a stimulus frequency of 20 Hz, the change in LDF was
      significantly different from the change in TLBF (p < 0.001). We conclude from our
      findings that during high-frequency hepatic nerve stimulation, LDF underestimates
      TLBF.

PMID- 9176728
TI  - Ultrastructure of the isthmic nucleus and identification of the synaptic contacts
      received by the neurons of the crossed isthmotectal projection in Rana esculenta.
AB  - The isthmic nucleus receives its major input from the ipsilateral optic tectum
      and projects to both tecta. It has been regarded as a relay station that is not
      involved in further processing of visual information. Recent studies on the
      connectivity and neurochemistry of this nucleus yielded substantial new data
      suggesting a more important role as being a simple relay. Since data on the
      ultrastructure of this nucleus are scarce the aim of this study was to obtain
      further information about the synaptic organisation of the nucleus. The frog Rana
      esculenta was used for our studies. The projection neurons of the isthmic nucleus
      were retrogradely labelled with HRP via the crossed isthmotectal tract. The
      tracer has been visualised with the diaminobenzidine reaction and the synaptic
      contacts have been studied with the electron microscope. Analysis of the synapses
      and profile types showed that both symmetrical and asymmetrical synapses are
      present in the nucleus. The dominant synapse type is axodendritic. Presynaptic
      profiles contain primarily round clear vesicles, but flattened vesicles also
      occur. Besides the axodendritic synapses, axosomatic contacts were also found in
      low number. Two kinds of dense core vesicles (large round or large elongated)
      were seen coexisting in the above described terminals. Close membrane appositions
      between the cortical cells suggest the probability of electrotonic coupling.
      Analysis of the relative frequency of synaptic profiles in different locations of
      the nucleus showed that the medullar neuropile is inhomogeneous. Our data support
      the view that the organisation of the isthmic nucleus is more diverse than that
      has been supposed until recently raising new functional considerations regarding
      isthmic information processing.

PMID- 9176729
TI  - Morphological diversity of nitric oxide synthesising neurons in mammalian
      cerebral cortex.
AB  - Neocortical neurons that utilise nitric oxide (NO) differ in morphology in
      different mammalian species. In the present study we examine these differences in
      the neocortex of mouse, rat, guinea-pig, rabbit, cat and monkey using
      histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH
      d) and immunocytochemistry for nitric oxide synthase (NOS), gamma amino-butyric
      acid (GABA), calbindin (CB), parvalbumin (PV) and calretinin (CR). NO neurons are
      non-pyramidal and can be divided into two distinct types, both of which react for
      NOS and NADPH-d. Type I neurons have a relatively large soma with heavy reaction
      product filling even the fine processes. They occur in all species, mainly near
      the border between the cortex and white matter, with fewer in the cortex, mostly
      in the superficial layers (II-IV). Type II cells are more numerous, smaller, and
      lighter in reactivity. They are in all species examined here except rodents, and
      in all cortical layers, but mainly layers II-IV. Most intracortical and some
      subcortical Type I neurons express GABA. A few intracortical Type I cells contain
      CB. All Type II cells express GABA and most also CB. Neither Type I nor Type II
      cells stain for PV or CR. We conclude that there is a tendency for a reduction of
      Type I cells, and increase of Type II, in mammalian neocortex with phylogeny.

PMID- 9176730
TI  - A common morphological response of astrocytes to various injuries: "dark"
      astrocytes. A light and electron microscopic analysis.
AB  - Our previous studies showed that neurons became argyrophilic following different
      kinds of brain injuries. In the present study we demonstrated that astrocytes
      could also become argyrophilic following compressive or concussive head injuries
      and following intraperitoneal administration of pentylenetetrazole or kainic
      acid. Furthermore the soma, nucleus and processes of these argyrophilic
      astrocytes were shown in other preparations to be hyper-basophilic with the light
      microscope, and hyper-electron dense and shrunken at the ultrastructural level.
      When the head injuries were inflicted either at the 15th min. of perfusion
      fixation or at the 30th min. of transcardial perfusion with chilled physiological
      saline, several astrocytes also became argyrophilic, hyper-basophilic, shrunken
      and hyper-electron dense. These data indicate that (i) the intracellular
      pathological event in these astrocytes is similar to that of "dark" neurons or
      "dark" cells of non-neural tissues, (ii) the formation of "dark" astrocytes can
      be independent of the actual state of metabolism, and (iii) the "dark"
      morphological state of astrocytes might have a role in neuropathological
      processes.

PMID- 9176732
TI  - Cortical scaling in mammals: a repeating units model.
AB  - A simple scaling model germane to the gyrencephalic mammalian cortex is proposed.
      The model aims to account for the empirical scaling of morphometric variables
      such as cortical thickness, surface area and volume, as a function of brain size.
      Several assumptions are made. Gyrencephalic cortices are assumed to be modular in
      construction, comprised of identical repeating units. Both the number and size of
      cortical units are assumed to increase with increasing brain size. The shape of
      the brain and of the repeating units are assumed not to vary systematically with
      brain size. The surface-density of repeating units is taken to be invariant. The
      model exponents for cortical thickness, folded surface area and volume, each as a
      function of cerebral volume, are one-ninth, eight-ninths and one, respectively.
      These discrete model exponents, and others, are in reasonable agreement with a
      diverse body of scaling data, both phylogenetic and ontogenetic. One
      interpretation is that phylogenetic scaling simply reflects ontogenetic scaling,
      extended over a wide range of adult brain sizes. The model is confined to
      ontogenetic/phylogenetic scaling. It is suggested that the model exponents are
      not adaptive, in the usual sense of that term.

PMID- 9176731
TI  - Glial fibrillary acidic protein and vimentin in radial glia of Ambystoma
      mexicanum and Triturus carnifex: an immunocytochemical study.
AB  - The molecular characterization of glial lineage cells in two urodele species,
      Ambystoma mexicanum and Triturus carnifex, has been investigated
      immunocytochemically with antibodies directed against intermediate filament
      proteins, glial fibrillary acidic protein (GFAP) and vimentin. Ambystoma
      astroglia shows clear GFAP-immunopositivity and vimentin-immunonegativity. The
      condition in Triturus is quite the opposite, showing only a strong vimentin
      immuno-reaction. In these urodele brain the astroglia is represented by radial
      glial cells with their somata lining cerebral ventricles (tanycytes). Each of
      them originates a thick process which radially crosses the periventricular gray
      matter and branches within the neuropil. These glial fibers originate endfeet on
      the subpial surface and on blood vessel wall. Only in the spinal cord cell bodies
      of immunopositive radial glia are displaced from the ependyma of the central
      canal which is almost immunonegative except the tanycytes forming the dorsal and
      ventral septum. No mammalian-like astrocytes appear neither in brain nor in
      spinal cord. The interspecific difference in the intermediate filament protein
      expression in radial glial cells could suggest that as regards this character
      Triturus retains a more immature condition than Ambystoma.

PMID- 9176733
TI  - Brain structure volumes in the mole rat, Spalax ehrenbergi (Spalacidae, Rodentia)
      in comparison to the rat and subterrestrial insectivores.
AB  - Natural blindness and a subterranean, digging mode of life demand peculiar
      adaptations of the central nervous system in the mole rat Spalax ehrenbergi,
      which are the focus of this quantitative investigation. Volumes of 25 brain
      structures in Spalax were evaluated allometrically, using the least encephalized
      mammalian species, the Madagassian hedgehog-like tenrecs (Tenrecinae) as a
      reference base, and their sizes compared with those of the rat (as a more
      generalized representative of rodents) and of some subterranean Insectivora. The
      allometric approach reveals that Spalax has a larger brain than tenrecs and the
      rat. Within the brain, the neocortex and diencephalon are well developed, an
      observation also made in other mammalian species with a relatively high
      encephalization. An unique feature in Spalax is the enlargement of motor
      structures of the brain, such as the cerebellum (and cerebellar nuclei), and the
      striatum. Most conspicuous is the large size of the nucleus motorius nervi
      trigemini, reflecting the importance of masticatory muscles for the special
      digging technique, which demand an intense use of the teeth for loosening the
      soil.

PMID- 9176734
TI  - Changes in CD44 and ApoE immunoreactivities due to retinal pathology of man and
      rat.
AB  - In cases of retinal light damage, glaucoma, or senile macula degeneration, the
      loss of retinal neurons is thought to cause alterations of glial cells. We
      performed immunocytochemical studies on retinae of (i) healthy rats and human
      donors, (ii) rats exposed to enhanced illumination for 24 months, a procedure
      which leads to complete loss of photoreceptor cells, (iii) a human donor who had
      suffered from senile macula (photoreceptor cell) degeneration, and (iv) human
      donors who had suffered from glaucoma, known to be accompanied by a loss of
      ganglion cells and other retinal neurons. Furthermore, Muller cells were
      enzymatically isolated from human glaucomatous retinae. All preparations were
      subjected to immunocytochemistry for CD44 antigen and Apolipoprotein E (ApoE). In
      normal rat and human retinae, CD44 immunoreactivity was observed in the
      microvillous sclerad processes of Muller cells: in human retinae, perivascular
      (astro-)glial cell processes were also CD44 immunopositive. ApoE immunoreactivity
      was only found in some perivascular (astro-)glial cell processes of human
      retinae. Both rat and human Muller cells respond to photoreceptor cell damage by
      increased, and ectopic, expression of the CD44 antigen. Increased ApoE
      immunoreactivity was found in Muller cells from degenerative human retinae, but
      rarely in light-damaged rat retinae. It is concluded that degeneration-related
      reorganization involves enhanced expression of the glial cell adhesion molecule
      CD44 as well as elevated activity of the glial lipid transport molecule ApoE.

PMID- 9176735
TI  - The dorsal tegmentum of the pontomesencephalic junction of the rat-
      immunohistochemistry (choline acetyltransferase, tyrosine hydroxylase, substance
      P) and NADPH-diaphorase histochemistry in frontal and horizontal sections.
AB  - 37 complete frontal and horizontal series of rat brain were studied to compare
      the distribution of choline acetyltransferase- (ChAT), tyrosine hydroxylase-
      (TH), substance P- (SP), calbindin D- (Calb) and NADPH-diaphorase (NADPH-d)
      positive cells within the cytoarchitectonic borders of the latero-dorsal
      tegmental nucleus (L-D) and its neighbourhood. We found the same distribution,
      number and morphology of NADPH-d-positive cells and ChAT-positive cells.
      Rostrally, there are no borders between NADPH-d-positive cells of L-D and NADPH-d
      positive cells of the lateral part of the dorsal raphe nucleus. Only a few TH
      positive cells are intermingled with ChAT/NADPH-d-positive cells at the lateral
      border of L-D. TH-positive cells are larger or the same size as cholinergic
      neutrons. Locus coeruleus and its rostral part is full of TH-positive cells and
      their fibres run ventromedially towards L-D. Barrington's nucleus appears in
      double staining (ChAT and TH or NADPH-d and TH) as an empty area bordered by ChAT
      or NADPH-d-positive cells of L-D and TH-positive fibres of the locus coeruleus.
      Some of these fibres run through the Barrington's nucleus. The shape and size of
      SP-positive neurons is the same as ChAT- and NADPH-d-positive neurons. SP
      positive neurons are sparsely distributed in all parts of L-D, but there are only
      a few SP-positive cells in its medial part. About 50% of the ChAT- and NADPH-d
      positive cells are also SP-positive. Results are expressed by figures in three
      representative frontal sections and one horizontal section through the dorsal
      mesopontine tegmentum.

PMID- 9176736
TI  - Coexistence of mu-opioid receptor-like and substance P-like immunoreactivities in
      the cat dorsal root ganglionic neurons.
AB  - Coexistence of mu-opioid receptor (MOR)-like immunoreactivity (LI) and substance
      P (SP)-LI in the neurons of the cat dorsal root ganglia (DRG) was examined by a
      double immunofluorescence histochemical method. Approximately 91% of SP-LI
      neurons in the DRG showed MOR-LI. However, SP-LI was exhibited in approximately
      28% of the neurons labeled with MOR-LI. These morphological findings indicated
      that the MOR exist on most of the primary afferent SP-containing terminals, and
      suggest that MOR may regulate SP release from the primary afferent terminals in
      the cat dorsal horn.

PMID- 9176737
TI  - Persistence of layer IV in the primary motor cortex (area 4) of children with
      cerebral palsy.
AB  - The normal development of the human primary motor cortex is characterized by a
      cytoarchitectonic transformation from the fetal, six-layered cortex to the adult,
      five-layered agranular cortex. The present study examines whether this
      transformation also occurs in children with cerebral palsy. Nissl-stained, serial
      sections through the left precentral gyrus of 14 children (age: 3-13 years) with
      cerebral palsy and from a control group without any clinically manifested
      disturbances of the motor system were analyzed. The widths of cortical layers,
      the laminar distributions of area 1 fractions occupied by cell bodies and
      neuropil, and the numerical densities and mean sizes of cell bodies were
      measured. In 5 cases of cerebral palsy, an inner granular layer (IV) persisted up
      to ages between 3 and 9 years. Layer IV was absent in other cases and in the
      controls. The persistence of layer IV was closely related to severe impairments
      of posture: all children with persistent layer IV were unable to maintain an
      upright posture. Cytoarchitectonic differences to controls were also found in
      other layers. Layer V, the major source of the pyramidal tract, was more narrow
      in children with cerebral palsy. The ratio between average cell body size for
      layers III and V was changed in the group of cerebral palsy. Thus, severe
      impairment of posture can be associated with disturbed cytoarchitectonic
      development of the motor cortex.

PMID- 9176738
TI  - The effect of high and low dosages of paraoxon in beta-naphthoflavone-treated
      rats.
AB  - Aliesterases (carboxylesterases) are serine esterases that can serve a protective
      role for the target acetylcholinesterase (AChE) during organophosphorus
      insecticide intoxication because the former esterases are alternate
      phosphorylation sites. The levels of aliesterase activity in liver and plasma and
      AChE activity in brain regions were investigated after the intravenous
      administration of paraoxon (P = O) into female rats. The rats were pretreated
      intraperitoneally with beta-napthoflavone (BNF), which decreases hepatic
      aliesterase activity following a 3 day in vivo treatment, and/or tri-o-tolyl
      phosphate (TOTP) to inhibit aliesterases. The liver aliesterases were inhibited
      less by P = O in BNF-treated rats than in control rats, which suggests that
      either BNF exposure may have resulted in aliesterases that are less sensitive to
      P = O inhibition or BNF may have altered P = O's availability. The BNF treatment
      did not seem to alter the degree of inhibition of the brain AChE activity
      following the low dosage of paraoxon (0.04 mg/kg). However, the brain AChE
      activity in the P = O/TOTP/BNF-treated rats was lower than that in the P = O/TOTP
      treated rats, suggesting that BNF also caused changes in systems affecting the
      disposition of P = O in addition to the changes in the hepatic aliesterases. At
      the high dosage of paraoxon (0.12 mg/kg), the AChE and aliesterase activities
      showed a pattern similar to that of the low dosage. This suggests that the
      aliesterases, as altered by BNF exposure, even when nearly completely inhibited,
      did not alter the response of the target enzyme, AChE, and, therefore, the
      magnitude of the toxic response.

PMID- 9176739
TI  - Protective action of dehydroascorbic acid on the Ah receptor-dependent and
      receptor-independent induction of lipid peroxidation in adipose tissue of male
      guinea pig caused by TCDD administration.
AB  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on lipid peroxidation,
      3H-Me-glucose (3H-Me-glu), and 14C-dehydroascorbic acid (14C-DHA) uptakes were
      studied in adipose tissue of male guinea pig. Under in vitro test conditions,
      using isolated adipose tissue in a culture medium (explant culture), TCDD reduced
      the uptake of 3H-Me-glu and 14C-DHA in a dose- and time-dependent fashion. The
      IC50 values of TCDD's action were 0.04 and 2 nM on 14C-DHA and 3H-Me-glu uptakes,
      respectively. TCDD (10 nM) also suppressed glucose transporting activity within
      15 minutes in explant-cultured adipocytes. Cytochalasin B (CB) and nonlabeled D
      glucose inhibited 14C-DHA uptake also in a dose-dependent manner. In addition,
      TCDD was found to induce lipid peroxidation in explant-cultured adipose tissue.
      This effect of TCDD was similar to that of a typical lipid peroxidation inducer,
      CCl4, and it was dose and time dependent. TCDD caused a statistically significant
      rise in lipid peroxidation at a concentration as low as 0.1 nM after 60 minutes
      of treatment in explant culture. Unexpectedly, the Ah receptor partial
      antagonists, 4,7-phenanthroline and alpha-naphthoflavone, did not fully
      antagonize TCDD-induced lipid peroxidation in explant-cultured adipocytes. In
      vivo treatment of TCDD also induced lipid peroxidation. Among seven organs of
      male guinea pig tested, the levels of lipid peroxidation in adipose tissue and in
      liver increased at 1 and 40 days following a single i.p. dose of TCDD (1
      microgram/kg). The results of an in vivo time-course study indicated that such an
      effect of TCDD was most pronounced after 40 days of treatment. Finally, we have
      tested the protective role of some antioxidants on TCDD-induced lipid
      peroxidation under explant-culture conditions. The results indicated that DHA,
      but not ascorbic acid, could completely abolish TCDD-induced lipid peroxidation.
      The protective effect of DHA on TCDD-induced lipid peroxidation was stronger than
      that of alpha-tocopherol and uric acid, and this effect was blocked by CB. We
      conclude from these studies that TCDD acts in this guinea pig tissue through two
      different routes: one is the Ah receptor-dependent route causing the reduction of
      the level of glucose transporters and subsequent decrease of cellular uptake of
      DHA and the other, the Ah receptor-independent route causing the overall lipid
      peroxidation. Nevertheless, it appears likely that both events are antagonized by
      DHA.

PMID- 9176740
TI  - Protection against acetaminophen-induced hepatotoxicity by L-CySSME and its N
      acetyl and ethyl ester derivatives.
AB  - We have recently observed that S-(2-hydroxyethylmercapto)-L-cysteine (L-CySSME),
      the mixed disulfide of L-cysteine and 2-mercaptoethanol, prevented cataracts
      induced in mice by acetaminophen (ACP) by functioning as a prodrug of L-cysteine
      and protecting the liver. This prompted the evaluation of the more lipophilic N
      acetyl (Ac-CySSME) and ethyl ester (Et-CySSME) derivatives of L-CySSME as
      proprodrug forms, as well as the "D" enantiomer, as hepatoprotective agents.
      Serum ALT levels were measured at 24 hours after a toxic but nonlethal dose of
      ACP that insured 48 hour survival of the animals. Since the increases in ALT
      produced were highly variable (even after log transformation) and complicated the
      statistical analyses, we calculated confidence intervals for the mean ALT levels
      for each treatment group. This enabled comparisons to be made of the efficacy of
      L-CySSME as well as Ac-CySSME and Et-CySSME with other representative prodrugs of
      L-cysteine, namely, 2(RS)-methylthiazolidine-4(R)-carboxylic acid (MTCA), L-2
      oxothiazolidine-4-carboxylic acid (OTCA), and N-acetyl-L-cysteine (NAC), in
      protecting the liver. It was shown that L-CySSME and MTCA administered
      intraperitoneally at 2.5 mmol/kg were superior to the other cysteine prodrugs at
      equimolar doses in protecting mice from hepatotoxicity elicited by a 400 mg/kg
      (2.65 mmol/kg) dose of ACP given i.p. 30 minutes prior to the prodrugs. The "D"
      form of CySSME was totally without protective effect. Oral doses of the prodrugs
      even at 2x the i.p. dose were less effective, although MTCA was the most
      protective.

PMID- 9176741
TI  - Drug metabolizing enzyme induction by benzoquinolines, acridine, and quinacrine;
      tricyclic aromatic molecules containing a single heterocyclic nitrogen.
AB  - Rats were treated with nitrogen-containing phenanthrene (3,4-, 5,6-, or 7,8
      benzoquinoline) or anthracene (acridine or quinacrine) derivatives at a dose of
      75 mg/kg, daily for 3 days. The hepatic drug metabolizing enzyme response ranged
      from no induction (quinacrine) through low (5,6-benzoquinoline), intermediate
      (acridine), and high (3,4-benzoquinoline) magnitude increases of only phase II
      enzymes, to induction of both phase I and phase II enzymes (7,8-benzoquinoline).
      The phase I enzyme response of 7,8-benzoquinoline was an induction of CYP1A. All
      three benzoquinolines, but neither anthracene derivative, elevated NAD(P)H
      quinone oxidoreductase activity. A similar pattern but of lesser magnitude was
      seen with glutathione S-transferase activity. 3,4-Benzoquinoline was the only
      agent to significantly increase microsomal epoxide hydrolase activity (2,3-fold).
      Both 3,4- and 7,8-benzoquinoline increased UDP-glucuronosyltransferase activity
      toward 4-nitrophenol (40% and 70%, respectively), but only the 3,4-isomer
      increased activity toward morphine (75%), diclofenac (75%), and testosterone
      (23%), and only the 7,8-isomer increased activity toward chloramphenicol (105%).
      3,4-Benzoquinoline elevated the hepatic mRNA concentration of UGT2B1 but not
      UGT1*6. Acridine treatment increased UDP-glucuronosyltransferase activity toward
      morphine (47%), 1-naphthol (28%), testosterone (19%), and estrone (19%).
      Quinacrine failed to elevate any UDP-glucuronosyltransferase activity and
      depressed activities toward testosterone and estrone by 20%. This study shows
      that some tricyclic aromatic compounds containing a single heterocyclic nitrogen
      atom have the potential for use as chemoprotective agents based upon their
      ability to selectively induce only phase II enzymes.

PMID- 9176743
TI  - In vitro toxicity testing of alcohol-soluble proteins from diploid wheat Triticum
      monococcum in celiac disease.
AB  - Peptic-tryptic digests of alcohol-soluble proteins from flours of 10 accessions
      of Trificum monococcum with contrasting storage protein compositions and bread
      making characteristics were found unable to agglutinate K562(S) cells even at a
      peptide concentration as high as 14 g/L, agglutination being strongly correlated
      with toxicity in celiac disease. When fractionated by affinity chromatography on
      Sepharose-6B coupled with mannan, peptic-tryptic digests separated into three
      fractions. Fraction C peptides were shown to agglutinate K562(S) cells, whereas
      peptides in fractions A and B and in the mixed fraction B + C were inactive,
      suggesting that fraction B contains "protective" peptides that interfere with
      toxic peptides in fraction C in their agglutinating activity. These results offer
      an opportunity to study the biochemical and genetic bases of wheat toxicity at
      the diploid level. Moreover, the reduced toxicity, if any, of Triticum monococcum
      in the celiac disease, along with the good grain characteristics of some
      "monococcum" accessions, greatly increases the economical prospects of this wheat
      species.

PMID- 9176742
TI  - The role of different cytochrome P450 isoforms in in vitro chloroform metabolism.
AB  - The two CHCl3 activation pathways have been studied in incubations at different
      oxygenation conditions with hepatic microsomes from control Sprague Dawley (SD)
      rats or SD rats treated with different cytochrome P450 inducers (acetone,
      phenobarbital, pyrazole, dexamethasone, and beta-naphthoflavone). The present
      results provide direct evidence that CHCl3 concentration is critical in
      determining the role of different cytochrome P450 isoforms (CYP) and the related
      effects of metabolic inducers. At 0.1 mM CHCl3 concentration, the only major
      contribution to its oxidative biotransformation in liver microsomes from
      untreated rats was due to CYP2E1, as shown by metabolic inhibition due to 4
      methylpyrazole or by anti-CYP2E1 antibodies. Moreover, animal treatments with
      acetone and pyrazole increased the production of adducts of phosgene to
      microsomal phospholipid by about 10-15 times. At 5 mM chloroform, in control rat
      liver microsomes, CYP2B1/2 was the major participant responsible for chloroform
      activation, while CYP2E1 and CYP2C11 were also significantly involved.
      Consistently, at this chloroform concentration, the effect of phenobarbital
      (CYP2B1/2 inducer) was maximal, producing very high levels of adducts. The
      reductive pathway was expressed at 5 mM CHCl3 only and was not significantly
      increased by any of the inducers used. Moreover, it was not inhibited by
      metyrapone and 4-methylpyrazole or by anti CYP2C11 antibodies. Therefore, it may
      be concluded that, in the range of chloroform concentrations tested, those CYPs
      involved in CHCl3 oxidative bioactivation do not participate in CHCl3 reduction.
      Chloroform oxidative metabolism in PB-microsomes could achieve very high absolute
      rates, much higher than those in C-microsomes; in contrast, the metabolic rates
      in AC- and PYR-microsomes remained within the activity levels observable in C
      microsomes at high chloroform concentration. Therefore, it can be argued that the
      CYP2B1/2-mediated induction of CHCl3 activation is the basis for the effect of PB
      in potentiating chloroform hepatotoxicity. Moreover, processes other than CYP2E1
      mediated metabolic induction may be more relevant in the ketones potentiation of
      chloroform-induced acute toxicity.

PMID- 9176744
TI  - Sinusitis in HIV-infected patients.
AB  - The purpose of this study is to retrospectively review the clinical, radiographic
      and laboratory characteristics, the therapy and evolution of sinusitis in HIV
      infected patients hospitalized between January 1, 1985 and July 31, 1994. We have
      observed 65 cases of sinusitis in 58 HIV-infected patients (77.6% classified as
      group C). Forty-five of 65 cases (69.2%) showed radiographic evidence of acute
      sinusitis; the remaining 20 cases (30.8%) showed chronic sinusitis. In 61 cases
      (93.8%) there were symptoms related to sinusitis. In 61 sinusitis cases
      antibiotics were administered. Although the majority of patients responded at
      least partially to antibiotic therapy, a complete resolution of clinical and
      radiographic signs was observed in only 47.4% of acute sinusitis cases. No
      resolution was observed in chronic sinusitis after treatment stop. Sinusitis
      appears to occur quite frequently in HIV-infected patients, is often related to
      non-specific symptoms, may be recurrent and is commonly refractory to treatment.

PMID- 9176745
TI  - Tazobactam-piperacillin compared with sulbactam-ampicillin, clavulanic acid
      ticarcillin, sulbactam-cefoperazone, and piperacillin for activity against beta
      lactamase-producing bacteria isolated from patients with complicated urinary
      tract infections.
AB  - The antibacterial activity of tazobactam-piperacillin was compared with that of
      sulbactam-ampicillin, clavulanic acid-ticarcillin, sulbactam-cefoperazone and
      piperacillin against beta-lactamase-producing bacteria isolated from patients
      with complicated urinary tract infections. Tazobactam-piperacillin showed a broad
      antibacterial spectrum against gram-negative and gram-positive bacteria. The
      minimum inhibitory concentrations (MIC90) of tazobactam-piperacillin were 6.25
      micrograms/ml against Escherichia coli, 1.56 micrograms/ml against Proteus
      mirabilis, 3.13 micrograms/ml against Proteus vulgaris, 6.25 micrograms/ml
      against methicillin-susceptible Staphylococcus aureus, and 6.25 micrograms/ml
      coagulase-negative methicillin-susceptible staphylococci. Against all beta
      lactamase-producing bacteria tested the antibacterial activity of tazobactam
      piperacillin was at least 4- to 64-fold stronger than that of piperacillin,
      clavulanic acid-ticarcillin, and sulbactam-ampicillin, and similar to or greater
      than that of sulbactam-cefoperazone except for E. coli.

PMID- 9176746
TI  - Randomized trial comparing netilmicin plus imipenem-cilastatin versus netilmicin
      plus ceftazidime as empiric therapy for febrile neutropenic bone marrow
      transplant recipients.
AB  - The aim of this study was to compare the clinical and microbiological efficacy of
      netilmicin plus imipenem-cilastatin (Net + Imi) vs netilmicin plus ceftazidime
      (Net + Cef) as empiric antimicrobial therapy in bone marrow transplant (BMT)
      febrile neutropenic patients (pts). Sixty-six pts undergoing BMT for
      hematological malignancies and solid tumors were randomized to receive Net + Imi
      or Net + Cef as first-line antibiotic therapy. A lasting return of temperature to
      normal and complete disappearance of either clinical or cultural signs of
      infection without any modification of therapy was considered as improvement; the
      persistence of fever after 72 hours, the addition of a third antibiotic or a
      protocol change was considered as failure. Sixty-nine episodes were randomized
      during the course of the trial; bacteriological evidence of infection was
      obtained in 17 (25%) febrile episodes. Overall outcome based on clinical
      responses was as follows: 80% of pts on Net + Imi responded compared to 73% of
      those on Net + Cef. For microbiologically documented infections response rates
      were 70% in Net + Imi group and 43% in the Net + Cef group (p = ns). Neither
      septic death nor toxicity were observed. Both empiric regimens were shown to be
      effective; Net + Imi appeared to be more effective in microbiologically
      documented infections but there was no statistical significance. In conclusion,
      both Net + Imi and Net + Cef are active and safe as empirical treatment of
      febrile episodes in neutropenic BMT pts.

PMID- 9176747
TI  - Chemotherapy of non small cell lung cancer. A prospectively randomized study of
      cisplatin-etoposide versus cisplatin-mitomycin-vinblastine.
AB  - Based on preclinical studies showing synergism between cisplatin and etoposide,
      we randomized patients with non small cell lung cancer (NSCLC) to receive either
      the above combination (cisplatin 100 mg/m2 day 1, etoposide 130 mg/m2 days 1-3)
      or the combination of cisplatin-mitomycin-c and vinca drugs (MVP) (cisplatin 100
      mg/m2, vinblastine 6 mg/m2, mitomycin 10 mg/m2 day 1), a regimen with a steady
      response rate. Partial responses were achieved in 12/44 (27%) of the cisplatin
      etoposide group and in 11/43 (26%) of the MVR group. No difference in median
      survival could be demonstrated between the two groups (36 weeks versus 38 weeks).
      Myelotoxicity and alopecia were more severe in the cisplatin-etoposide group.
      Compared to international experience both regimens exhibited a relatively low
      response rate. It seems that for NSCLC new agents are required.

PMID- 9176749
TI  - Cyclin D1, p53, mdm2, and Ki67 protein expression in preneoplastic lesions of the
      larynx.

PMID- 9176748
TI  - Intrapleurally instilled mitoxantrone in metastatic pleural effusions: a phase II
      study.
AB  - Thirty cases (breast cancer-20 cases, malignant lymphoma-4 cases, different
      malignancies-6 cases) of histologically/cytologically verified malignant pleural
      effusion (MPE) in 29 patients were treated with intrapleurally instilled
      mitoxantrone (30 mg). The therapy was well tolerated. At evaluation, 25 patients
      had died of progressive disease. The median survival was 3 months (range 0.3-21.3
      months). There were 26 responders (12 complete responses (CR), 14 partial
      responses (PR)), whereas 4 patients relapsed and 3 of these had an early relapse
      (within 3 months). Patients achieving PR or CR had a low risk (15%) of treatment
      failure. Five patients were subjected to a pharmacokinetic evaluation. This
      demonstrated rapidly declining plasma and pleural exudate levels of mitoxantrone
      within the first 6 hours. At 24 hours after instillation, mitoxantrone was only
      detected in circulating mononuclear cells. This study shows that mitoxantrone is
      efficacious in the treatment of MPE, and may represent a cost-effective
      alternative.

PMID- 9176750
TI  - Bcl-2 expression is related to poor differentiation and advanced clinical stage
      in laryngeal squamous cell carcinoma.

PMID- 9176751
TI  - Analysis of receptor phenotypes in operated breast cancer.

PMID- 9176752
TI  - Cytokeratin immunostaining reveals micrometastasis in negative hematoxylin-eosin
      lymph nodes of resected stage I-II (pT2-pT3) colorectal cancer.

PMID- 9176753
TI  - Anal canal cancer diagnosis: usefulness of serum tumor markers.

PMID- 9176754
TI  - p53 overexpression and mutation, chemoresistance and patient survival in oral and
      maxillofacial squamous cell carcinoma.

PMID- 9176755
TI  - Carcinoembryonic antigen: its role in malignant extraintestinal neoplasms.

PMID- 9176756
TI  - Laterocervical swelling as first sign of tumor.

PMID- 9176757
TI  - Analysis of the evolution of operated breast cancer.

PMID- 9176758
TI  - Surgical treatment of invasive carcinoma of the vulva: two different techniques.

PMID- 9176759
TI  - Conization of the uterine cervix: two different surgical techniques.

PMID- 9176760
TI  - Underestimation of ovarian pathology: a review.

PMID- 9176761
TI  - Isolated pelvic perfusion for inoperable advanced tumors: hyperthermic or hypoxic
      perfusion?

PMID- 9176762
TI  - Adjuvant therapy for resectable colorectal carcinoma with 5-fluorouracil portal
      vein infusion.

PMID- 9176763
TI  - Emergency surgery in colorectal cancer.

PMID- 9176764
TI  - Surgical treatment and prognostic factors in colon cancer.

PMID- 9176765
TI  - Intestinal anastomosis with valtrac biofragmentable ring. Our experience.

PMID- 9176766
TI  - Neoadjuvant treatment of local recurrence of rectal cancer: our experience.

PMID- 9176767
TI  - Carcinoma of the exocrine pancreas: our experience.

PMID- 9176768
TI  - Detection of hepatocellular cancer during screening of 1125 patients with chronic
      hepatitis virus infection.

PMID- 9176769
TI  - Gastrojejunal reconstruction after subtotal gastrectomy using stapler devices.
      Personal technique.

PMID- 9176770
TI  - Surgical technique and biomaterials for totally implanted port catheter systems.

PMID- 9176771
TI  - Inferior vena cava implant of permanent central venous access devices.

PMID- 9176772
TI  - A giant metastasis from follicular thyroid carcinoma.

PMID- 9176773
TI  - Medulloblastoma in an adult: case report.

PMID- 9176774
TI  - Malignant fibrous histiocytoma after radiation therapy for prostate cancer: case
      report.

PMID- 9176775
TI  - Paraneoplastic retinopathy: a novel autoantibody reaction associated with small
      cell lung carcinoma.
AB  - We present the case of a 74-year-old man with rapidly progressive bilateral
      visual loss, optic disc pallor, retinal arteriolar attenuation, and an abnormal
      electroretinogram with a 90% reduction in cone function and a 50% reduction in
      rod function. He was examined for a suspected cancer-associated retinopathy
      (CAR). Although he was found not to have expressed the previously reported 23-kd
      CAR antibody, high titers were found of an antibody to a 60-kd retinal protein,
      which as yet remains unidentified. An initial clinical search for an underlying
      cancer was unsuccessful, but 2 months later a mediastinal mass was found on chest
      x-rays, and biopsy confirmed a diagnosis of small-cell lung carcinoma. Combined
      therapy with oral corticosteroids and plasmapheresis resulted in a recovery of
      vision from counting fingers to 20/200 in the right eye and 20/40 to 20/25 in the
      left eye. Conventional chemotherapeutic management of the small-cell lung
      carcinoma was instituted, and the modest visual recovery was maintained. The
      visual improvement as well as lung tumor regression were accompanied by a decline
      in antibody titers from 1:2,000 pretreatment to 1:200 during the course of
      therapy. The absence of reactivity with the previously described 23-kd retinal
      antigen of the CAR syndrome does not exclude the diagnosis of paraneoplastic
      retinopathy in patients fitting the clinical profile of this disease.

PMID- 9176776
TI  - Loss of vision alone may result in seesaw nystagmus.
AB  - A patient is described who developed seesaw nystagmus (SSN) associated with
      progressive severe vision loss due to cone-rod dystrophy. She was otherwise
      neurologically normal, and findings on magnetic resonance imaging of the brain
      were normal, including optic chiasm, meso-diencephalic junction, and brainstem.
      The literature is reviewed on neurologically normal patients with SSN and ocular
      vision loss, and the hypothesis is presented that SSN may become manifest as a
      result of vision loss alone, even in patients with chiasmal lesions, without
      disruption of central ocular motility pathways.

PMID- 9176777
TI  - Optic nerve sheath fenestration for pseudotumor cerebri.
AB  - The objective of the study was to determine the efficacy of optic nerve sheath
      fenestration (ONSF) in eyes with progressive visual or field loss in pseudotumor
      cerebri in spite of medical therapy with oral Diamox. Visual data on 29 eyes of
      patients with pseudotumor cerebri who underwent ONSF at Bascom Palmer Eye
      Institute from 1987 to 1995 were studied retrospectively. These patients had
      progressive visual loss despite medical therapy. Visual acuity and fields were
      compared before and after surgery (within 1 and 6 months). During a mean follow
      up of 15.7 months (range, 1-50 months), visual acuity improved in four eyes
      (14%), was unchanged in 22 (76%) eyes, and worsened in three (10%) eyes. Visual
      fields improved in 10 (48%) eyes, remained unchanged in eight (38%) eyes, and
      worsened in three (14%) eyes (six were lost in long-term follow-up). There were
      four repeat surgeries in which vision was lost in one eye. Data from these
      patients indicate that ONSF improves or protects visual function in patients with
      pseudotumor cerebri who experience deteriorating visual acuity and fields in
      spite of medical therapy.

PMID- 9176778
TI  - Two types of oscillopsia in a patient with idiopathic vestibulopathy.
AB  - A patient with an idiopathic bilateral vestibulopathy described two types of
      oscillopsia, one induced by head movement, the other induced by changing pressure
      in the right external auditory canal. This is the first report of both types of
      oscillopsia occurring in the same individual and illustrates their different
      mechanisms and symptomatology.

PMID- 9176779
TI  - Gaze-evoked orbicularis oculi myokymia.
AB  - The cases of six patients with pronounced, persistent, isolated gaze-evoked
      orbicularis oculi myokymia (GEOM) discovered fortuitously are described. None had
      brain-stem lesions, and two had associated, unusual cranial synkinesis
      (trigeminofacial, hypoglossal-facial, and spinal accessory-facial). Additional
      features included asymmetric blinking and pseudoblepharoclonus in a third patient
      and buccopharyngeal synkinesis and post-deglutional tremors in a fourth. Ptosis
      and pupillary changes were absent. With the possible exception of one case, GEOM
      seems to be a congenital benign oculofacial synkinesis of brain-stem origin.

PMID- 9176780
TI  - Optic neuropathy in familial dysautonomia.
AB  - Optic atrophy, which is indicative of a CNS disorder, is a rarely described
      manifestation of familial dysautonomia (Riley-Day syndrome). As these patients
      are now living longer, the prevalence of optic neuropathy also may be increasing.
      We present a man with familial dysautonomia and visual loss resulting from optic
      atrophy and visual field defect suggestive of chiasmal pathology.

PMID- 9176781
TI  - High incidence of visual recovery among four Japanese patients with Leber's
      hereditary optic neuropathy with the 14484 mutation.
AB  - The 14484 mutation in the ND6 gene of mitochondrial DNA (mtDNA) is a genetic
      mutation associated with Leber's hereditary optic neuropathy (LHON) in Caucasian
      patients who show a high incidence of visual recovery. We evaluated four Japanese
      patients with LHON associated with the 14484 mutation who were negative for eight
      proposed secondary mutations. There was no family history of optic atrophy in
      three of the four patients. All four patients were initially diagnosed as having
      optic neuritis, either anterior (Cases 1 and 3) or retrobulbar (Cases 2 and 4),
      based upon their fundus findings and clinical history. Molecular genetic testing
      of mtDNA confirmed the diagnosis of LHON in all four patients. The three patients
      who experienced recovery had their vision return to 20/50 or better in both eyes.
      The patient who did not was a heavy consumer of alcohol and tobacco. These
      findings indicate that Japanese patients with the 14484 mutation have a visual
      prognosis similar to that of Caucasians with this mutation.

PMID- 9176782
TI  - Neuro-ophthalmic manifestations of Lyme disease.
AB  - Lyme disease is a multisystem disorder caused by infection with the Borrelia
      burgdorferi spirochete. The diagnosis of Lyme disease usually is based on several
      clinical criteria, with supportive data from laboratory testing. The presence of
      the bullseye skin lesion, erythema migrans, is the single pathognomonic
      criterion. In the 20 years since the initial description of Lyme disease in the
      United States, B. burgdorferi has been implicated as an etiologic agent in
      numerous ophthalmic and neuro-ophthalmic syndromes, involving most structures
      from the cornea to the cranial nerves. Neuro-ophthalmic and ocular manifestations
      of Lyme disease include meningitis with papilledema, cranial neuropathies,
      follicular conjunctivitis, nummular keratitis, and intraocular inflammation.
      Although an association with Lyme disease has been purported for numerous other
      syndromes, a definite causal relationship has not been proved in many cases.
      During a period of rapidly increasing awareness of Lyme disease, a high index of
      suspicion and poorly defined criteria for its presence have resulted in over
      diagnosis of Lyme disease. In the authors' experience, the incorrect diagnosis of
      Lyme disease initially has been made in patients with allergic conjunctivitis,
      keratoconus, morning glory syndrome, craniopharyngioma, meningioma, CNS lymphoma,
      paraneoplastic syndrome, multiple sclerosis, sarcoid, syphilis, and functional
      illness. Nevertheless, this treatable infection must be an important
      consideration in the differential diagnosis of certain ocular or neurologic
      diseases.

PMID- 9176783
TI  - Apraxia of eyelid opening after bilateral stereotaxic subthalamotomy.
AB  - The case of a patient with apraxia of eyelid opening and blepharospasm occurring
      during the course of idiopathic torsion dystonia and previously treated with
      stereotaxic subthalamotomy is presented. The anatomic basis of this lid movement
      disorder is suggested to be located in the rostral brain stem. There was a
      considerable amelioration after treatment with trihexyphenidyl.

PMID- 9176784
TI  - Why fatheads just don't see.

PMID- 9176785
TI  - Neuro-ophthalmology of the pregeniculate afferent visual system. Developments in
      1996 (Part II).

PMID- 9176786
TI  - Convergence nystagmus associated with spasmus nutans: a comment.

PMID- 9176787
TI  - Difficulties in interpreting optic disc fluorescein leakage in Leber's hereditary
      optic neuropathy.

PMID- 9176788
TI  - Histochemical and immunohistochemical localisation of elastic system fibres in
      focal reactive overgrowths of oral mucosa.
AB  - Eight specimens each of the following groups were investigated: gingival pyogenic
      granuloma, fibrous epulis, calcifying fibrous epulis, peripheral giant cell
      granuloma, giant cell fibroma (four gingival, four non-gingival), denture
      irritation hyperplasia and fibroepithelial polyp. These lesions have diverse
      histopathological appearances but the composition of their connective tissue is
      poorly defined. The elastic system consists of a complex mixture of glycoproteins
      that in normal oral mucosa form three differentially distributed fibre types;
      oxytalan, elaunin and elastic. The elastic system was investigated by Verhoeff's
      haematoxylin stain, aldehyde fuchsin staining and an anti-elastin monoclonal
      antibody. Elastin was identified in all fibroepithelial polyps and denture
      irritation hyperplasias, but in none of the other lesions. In particular, this
      identified a distinct difference in the extracellular matrix between the giant
      cell fibroma and fibroepithelial polyp. Many of the epulides included only
      oxytalan fibres, but the presence of oxytalan fibres did not follow any pattern
      within either a single lesion group, or between different lesions. However, the
      presence of oxytalan fibres in the absence of elastin does not necessarily
      support a periodontal ligament origin for reactive epulides.

PMID- 9176789
TI  - Central giant cell granulomas of the jaws: phenotype and proliferation-associated
      markers.
AB  - Central giant cell granulomas (CGCGs) are jaw tumors of unknown origin that often
      exhibit an aggressive, though unpredictable, clinical course. The purpose of this
      study was to determine the immunoprofile of the mononuclear cells that seem to be
      responsible for the biologic behavior of these tumors. Numbers of cells in cell
      cycle were also determined and compared in clinically aggressive and non
      aggressive CGCGs. Sixteen aggressive and 12 non-aggressive CGCGs were
      immunohistochemically stained with antibodies to CD34, CD68, factor XIIIa, alpha
      smooth muscle actin, prolyl 4-hydroxylase, Ki-67, and p53 protein. Cell
      populations and numbers of cells in cell cycle were determined through
      microscopic quantitative assessment. CD34-positive cells were limited to support
      vessels. CD68-positive mononuclear cells constituted a small population of cells
      in all tumors. With two exceptions, factor XIIIa-positive cells were rarely seen.
      Alpha-smooth muscle actin staining was present in approximately half the tumors,
      and occasionally large numbers of positive cells were seen. Most mononuclear
      cells were positive for fibroblast-associated antigen. No phenotypic differences
      were detected between aggressive and non-aggressive tumors. P53 protein did not
      appear to be overexpressed in CGCGs. Ki-67 staining showed that only mononuclear
      cells were in cell cycle, and that there were no differences between aggressive
      and non-aggressive tumors. We conclude that CGCGs are primarily fibroblastic (and
      myofibroblastic) tumors in which macrophages appear to play a secondary role.
      Tumor cells show no differentiation toward endothelial cells or macrophage
      related dendrocytes (factor XIIIa). Cellular phenotypes and numbers of cells in
      cell cycle are similar in both aggressive and non-aggressive tumors.

PMID- 9176790
TI  - Oral granular cell tumours: a histological and immunocytochemical study.
AB  - In a series of nine cases of intra-oral granular cell tumors (GCTs) an attempt
      was made, using both histochemical and immunocytochemical methods, to determine
      whether these tumours show Schwann-cell or neuroendocrine differentiation.
      Positive immunostaining with protein gene product 9.5 (PGP 9.5), neurone-specific
      enolase (NSE) and S-100, in contrast to predominantly negative immunostaining in
      12 cases of neurilemmoma of the head and neck, and a similar pattern of staining
      with luxol fast blue to five known neuroendocrine tumours, strongly suggests that
      granular cell tumors may be neuroendocrine in nature.

PMID- 9176792
TI  - Expression of CD1 and HLA-DR by Langerhans cells (LC) in oral lichenoid drug
      eruptions (LDE) and idiopathic oral lichen planus (LP).
AB  - Numbers of Langerhans cells (LC) expressing the common thymocyte antigen (T6/CD1)
      are similar in oral lichen planus (LP) and in normal oral epithelium; however,
      expression of class II major histocompatibility antigens (HLA-DR/Ia) by
      Langerhans cells is greater in lichen planus than in normal epithelium, a
      phenomenon believed to be associated with activation and antigen presentation.
      This study quantified the numbers of T6+ve and HLA-DR + ve Langerhans cells in
      oral lichen planus and lichenoid drug eruptions (LDE) to investigate whether
      differences may reflect differing routes of antigen presentation. Six patients
      with oral lichenoid drug eruptions and six control idiopathic oral lichen planus
      patients had lesional biopsies. An immunoperoxidase technique was used to
      demonstrate binding of T6 and HLA-DR antibodies to identify dendritic
      intraepithelial cells as Langerhans cells and activated Langerhans cells,
      respectively. In lichenoid drug eruptions, the number of HLA-DR + ve LC was
      significantly lower than the number of T6 + ve LC (P < 0.05), whereas in
      idiopathic lichen planus the numbers of T6 + ve and HLA-DR + ve LC did not differ
      significantly (P = 0.20). The results provide evidence for differences in the
      routes of antigen presentation in lichenoid drug eruptions and idiopathic lichen
      planus.

PMID- 9176791
TI  - Apoptosis-associated markers in oral lichen planus.
AB  - Hypothesizing that loss of basal cells in oral lichen planus is due to apoptosis,
      we evaluated LP specimens for apoptosis-regulating proteins [positive regulators
      Bcl-xS, Bax, Fas/Fas-ligand, p53, and negative regulators (anti-apoptotic) Bcl-2,
      Bcl-xL and compared results with reactions in normal mucosa and chronically
      inflamed gingiva. Also, sections were evaluated with an in situ TUNEL assay that
      identifies apoptotic DNA fragments. Basal keratinocytes in normal buccal mucosa,
      nonspecific gingivitis, and LP were negative for Bcl-2 protein, but melanocytes
      and lymphoid cells were positive. Keratinocyte staining for Bcl-x was negative to
      weak in normal buccal mucosa and gingivitis, and moderate in LP. Keratinocytes
      (especially upper prickle cells) in all tissues stained similarly for Bax at weak
      to moderate levels. Also, no differences in Fas and Fas-ligand staining were
      evident. Prominent p53-positive staining was seen in all LP biopsies (10-100% of
      basal keratinocytes) but not in normal buccal mucosa and gingivitis. Few basal
      keratinocytes in 5/10 LP cases exhibited a positive in situ signal for DNA
      fragment-associated apoptosis. That the Bcl-2 family of proteins and Fas/Fas
      ligand were detected in normal and diseased tissues, and were occasionally
      expressed differently in oral LP, supports the notion that apoptosis is a
      potential mechanism of keratinocyte loss, especially in LP. The pattern of p53
      staining in oral LP suggests over-expression of wild-type protein; a phenomenon
      that would arrest the cell cycle to allow repair of damaged DNA, or trigger
      apoptosis. While immunohistochemical evidence for apoptosis-associated basal
      keratinocyte death in LP was slight, it appeared that it may be p53 protein, and
      possibly Bcl-x associated.

PMID- 9176793
TI  - Triclosan inhibits sodium lauryl sulphate-induced changes in expression of
      cytokeratin genes in hamster cheek pouch epithelium.
AB  - Triclosan is known to reduce the untoward side effects of sodium lauryl sulphate
      (SLS). The aim of the present study was to determine whether triclosan can
      inhibit SLS-induced changes in expression of cytokeratin (CK) genes in hamster
      cheek pouch epithelium. With a hybridohistochemical technique, using specific
      human cRNA probes, hamster CK mRNAs were identified by immunological detection of
      heterologous hybrids. In contrast to application of SLS-containing paste,
      application of paste containing SLS together with triclosan produced no marked
      changes in expression and distribution patterns of CK mRNAs, compared to the
      normal cheek pouch epithelium. Therefore, we may accept that triclosan inhibits
      the effect of SLS on CK gene expression. However, the mechanism of this
      protection remains elusive. Conversely, the epithelial hyperplasia induced by
      application of SLS was histologically identical to that induced by application of
      SLS and triclosan. This suggests that the changes in CK gene expression
      identified in the present study are not a simple consequence of epithelial
      hyperplasia, but rather are specific to the irritating agent. Establishment of
      the fact that SLS may influence gene expression, and that this may be prevented
      by triclosan, may be helpful in research on the cytological effects of SLS and
      the elucidation of protection mechanisms of triclosan against side effects of
      SLS.

PMID- 9176794
TI  - Anti-Toxoplasma gondii immunoglobulins A and G in human saliva and serum.
AB  - Paired human saliva and serum samples from 60 individuals were tested for
      specific IgA and IgG antibodies to Toxoplasma gondii. The study in both fluids
      was carried out by indirect immunoenzymatic assay (ELISA). Saline antigenic
      extract of T. gondii was used to coat plastic surfaces upon which the samples
      were then incubated; monospecific conjugates of anti-IgA and anti-IgG-peroxidase
      were then incubated with the samples after a washing procedure to separate the
      unbound antibodies. The enzymatic activity was measured and the results expressed
      in terms of ELISA index. Toxoplasma-specific IgG antibodies were detected in 43
      of the serum samples (71.7%) and in 12 of the saliva samples (20.0%) whereas
      Toxoplasma-specific IgA antibodies were detected in 18 of the serum samples
      (30.0%) and in 12 of the saliva samples (20.0%). No association was observed when
      the Toxoplasma-specific IgG reactive and non-reactive serum samples were compared
      with the reactive and non-reactive saliva samples for this class of
      immunoglobulin. On the other hand, a significant association was observed when
      the Toxoplasma-specific IgA reactive and non-reactive serum samples were compared
      with the reactive and non-reactive saliva for this type of antibody. In
      conclusion, our results show that the detection of salivary IgA reflects the
      serum level of this isotype but salivary IgG does not. Moreover, the isolated
      detection of salivary IgG may not contribute to epidemiological studies of
      chronic toxoplasmic infections.

PMID- 9176795
TI  - Search for human herpesvirus 6, human cytomegalovirus and varicella zoster virus
      DNA in recurrent aphthous stomatitis tissue.
AB  - In the present study, the involvement of human herpesvirus 6 (HHV-6), human
      cytomegalovirus (HCMV) and varicella zoster virus (VZV) in the aetiology of
      recurrent aphthous stomatitis (RAS) was investigated using the polymerase chain
      reaction (PCR). Biopsies from 21 RAS patients were analysed, and 20 oral lichen
      planus (OLP) and 13 normal biopsies were tested as controls. HHV-6-DNA was
      detected in six of the RAS samples whereas VZV-DNA and HCMV-DNA were not detected
      in any RAS samples. In the OLP samples, four biopsies were positive for HHV-6-DNA
      and two were positive for HCMV-DNA. One sample from this group was positive for
      both HHV-6-DNA and HCMV-DNA. VZV-DNA was not found in any RAS or OLP biopsies. No
      viral DNA was present in any normal control biopsies. These results do not
      support an aetiological role for HCMV and VZV in RAS, although the possible
      involvement of HHV-6 cannot be excluded.

PMID- 9176796
TI  - Mucinous adenocarcinoma of the sublingual gland.
AB  - A case of mucinous (colloid) adenocarcinoma of the sublingual gland is reported.
      Adenocarcinomas associated with large pools of extracellular mucin are extremely
      rare in the major salivary glands. Analysis of the tumor for cytokeratin
      expression, estrogen and progesterone receptors was performed. Predominantly, the
      tumor expressed cytokeratins 7, 8, 18 and 19 that are commonly found in simple
      epithelia, and to a lesser degree cytokeratins 4 and 13 which are usually found
      in complex epithelia. Staining for estrogen and progesterone receptors was
      negative. No other cancer has been detected for three years after the first
      examination. The tumor is considered to be a primary mucinous adenocarcinoma of
      the sublingual gland.

PMID- 9176797
TI  - Paediatric Airway Clinic: an 18-month experience.
AB  - OBJECTIVE: The management of paediatric airway disease is an integral aspect of
      paediatric otolaryngology. Recently, paediatric tertiary referral centres have
      developed centres of excellence for various aspects of paediatric care. The
      Pediatric Otolaryngology Airway Clinic at The Children's Hospital of Alabama, was
      developed as a regional referral centre for the management of children with
      difficult airway problems. Primary participants include the paediatric
      otolaryngologist, the airway management nurse, and the speech pathologist, in
      addition to other health care personnel. Over an 18-month period, 195 patients
      were seen in the clinic. The purpose of this study was to assess both the
      demography and the airway pathology in this patient population-specifically
      evaluating presenting diagnoses, diagnostic evaluation techniques, surgical
      intervention, geographic and racial distribution, insurance coverage, and
      referral patterns. CONCLUSION: This multidisciplinary approach to the management
      of children with chronic tracheotomies and other conditions involving the airway
      provides a unique environment that optimizes care for these complex patients.

PMID- 9176798
TI  - Informed consent in head and neck surgery: how much do patients actually
      remember?
AB  - OBJECTIVE: This study was conducted to evaluate the effectiveness of informed
      consent in head and neck surgery by testing patient recall of potential
      complications from thyroidectomy, parathyroidectomy, and parotidectomy. DESIGN: A
      prospective design was used. SETTING: The setting was an academic tertiary care
      centre. METHODS: Fifty-four patients undergoing thyroidectomy, parathyroidectomy,
      or parotidectomy were consented by verbal contact by the operating surgeon with a
      specific preoperative checklist of complication and side effects. One week to 2
      months after consent, the patients were surveyed for recall of potential
      complications. MAIN OUTCOME MEASURES: Rate of recall was related to various
      parameters including patient age, sex, level of education, occupation, and length
      of time from the consent interview to the recall interview. RESULTS: The overall
      recall rate for all procedures was 48%. Those patients who recalled over 50% of
      the complications were younger (p = .04) and better educated (p = .04). The
      gender of the patients did not appear to influence recall success (p = 1.00),
      even when facial scar or paralysis was considered. CONCLUSION: A significant
      relationship exists between education level and patient age and the rate of
      patient recall of potential complications of surgery.

PMID- 9176799
TI  - IL-4 and IL-13 expression in chronic sinusitis: relationship with cellular
      infiltrate and effect of topical corticosteroid treatment.
AB  - OBJECTIVE: Chronic sinusitis with allergy (ACS) and without allergy (NCS) are
      inflammatory diseases with considerable morbidity. The present study was
      undertaken to investigate, by in situ hybridization, the expression of IL-13 and
      IL-4 mRNA in sinus biopsy sections. METHOD: Specimens were obtained from subjects
      with NCS (n = 12), ACS (n = 13), ACS on steroid therapy (n = 11), and normal
      controls (n = 11). The composition of the inflammatory infiltrate was also
      examined in all cases. RESULTS: The number of cells expressing IL-4 and IL-13
      transcripts was significantly higher in subjects with ACS compared to normal
      controls. In contrast, the numbers of IL-13 but not IL-4 mRNA-positive cells were
      increased in the NCS subjects compared to the normal controls. IL-4 and IL-13
      mRNA expression was suppressed in ACS subjects on topical steroid therapy
      compared to untreated patients. There was no significant difference in the
      numbers of eosinophils between the ACS subjects treated with steroids and those
      who were not treated, but the steroid-treated patients demonstrated significantly
      higher numbers of CD8+ cells in the sinus mucosa. Increased numbers of CD8+ cells
      were also observed in subjects with NCS compared with ACS subjects and normal
      controls. CONCLUSIONS: These results demonstrate that increased IL-13 expression
      is an important feature of allergic and nonallergic patients with chronic
      sinusitis. Furthermore, our data indicate that IL-13 and IL-4 are under
      differential regulation in NCS subjects.

PMID- 9176800
TI  - Preventing alar necrosis in using a Foley catheter for the control of posterior
      epistaxis.

PMID- 9176801
TI  - Predicting postlaryngectomy voice outcome in an era of primary tracheoesophageal
      fistulization: a retrospective evaluation.
AB  - OBJECTIVES: Not all laryngectomees appear to have the same potential to develop
      functional spoken communication. Our goal was to evaluate voice outcome in
      different functional subgroups of laryngectomees and to identify physical and
      demographic factors associated with success and failure to achieve functional
      spoken communication. DESIGN: Retrospective chart review. SETTING: Surgery was
      performed at a tertiary care hospital. Multidisciplinary follow-up was conducted
      at weekly head and neck clinics held at the associated regional cancer centre.
      Voice rehabilitation procedures took place in both settings. PATIENTS: Sixty-four
      consecutive patients who had undergone total laryngectomy during the era of
      primary tracheoesophageal fistulization (TEF) at this facility. Patients were
      subdivided into four groups according to whether they had undergone primary TEF,
      or whether this had been contraindicated by locoregional factors of TEF
      candidacy/performance status, or both. INTERVENTIONS: Primary TEF was performed
      whenever technically feasible and traditional TEF candidacy criteria were met.
      Voice rehabilitation procedures were initiated prior to discharge. OUTCOME
      MEASURES: A judgement of voice outcome was assigned based on documentation on at
      least one of three patient treatment records by a physician or speech-language
      pathologist that a patient had demonstrated functional spoken communication
      within the clinical setting. RESULTS: Forty-five of 64 patients (70%) achieved
      functional spoken communication. Six laryngectomized subgroups were ultimately
      identified and characterized. Voice outcome varied considerably between these
      subgroups. Prelaryngectomy communication status and age emerged as predictors of
      voice outcome. CONCLUSIONS: Voice outcome is related to several factors present
      prior to or at laryngectomy. Different combinations of such factors create
      various postlaryngectomy recovery streams for which voice outcome may be
      predicted more specifically.

PMID- 9176802
TI  - The Paediatric Cochlear Implant Program at the Hospital for Sick Children,
      Toronto.
AB  - Ontario has a province-wide program for provision of cochlear implants. Toronto's
      Hospital for Sick Children is one of three designated centres that service the
      paediatric population. This cochlear implant program was established in 1989.
      Since that time, 37 children (as of May 1996) have been provided with cochlear
      implants. The program also services Ontario residents who were implanted
      elsewhere. In the following, we provide a detailed description of the program,
      including the processes through which children are selected as candidates, the
      follow-up studies that we carry out, and the roles of various health care
      professionals involved. We present a demographic survey of our patient population
      to date, and discuss some of the important issues relating to candidacy.

PMID- 9176803
TI  - Distortion-product otoacoustic emissions and glycerol on the guinea pig hydropic
      ear.
AB  - OBJECTIVE: The aim of the present work was to investigate the therapeutic effects
      of glycerol on the distortion-product otoacoustic emissions in guinea pigs in
      which experimental endolymphatic hydrops had been surgically induced. METHODS:
      Thirty albino guinea pigs were used. The experimental protocol considered three
      groups of guinea pigs (10 animals each). Group 1 received no drug treatment,
      while group 2 and 3 were given glycerol orally 0.75 and 0.50 g/kg of body weight
      once a day for 24 days. RESULTS: The animals treated with glycerol showed an
      improvement of the distortion-product emission responses in the middle
      frequencies. This effect was not observed in the higher frequency region. This
      effect was evident 7 days after glycerol administration in the guinea pigs
      treated with a dose of 0.75 g/kg. The 0.50 g/kg dosage gave evidence of
      ameliorating effects 14 days after treatment. CONCLUSION: Glycerol given orally
      resulted in an improvement of distortion-product otoacoustic emissions in the
      guinea pig. Further studies are necessary before the effect of such a treatment
      can be assessed in humans.

PMID- 9176804
TI  - Safety of topical ear drops containing ototoxic antibiotics.
AB  - OBJECTIVE: Topical application of ear drops containing ototoxic antibiotics is
      commonly used for treatment of middle ear diseases. Because of their ototoxic
      potential, we evaluated the safety of these ear drops in clinical use. METHODS:
      The study included 446 children who underwent myringotomy and the insertion of
      tympanostomy tubes. Three hundred and fifty-eight received preventive treatment
      after the operation with polymyxin B-neomycin-dexamethasone ear drops for 2
      weeks; 88 did not receive any ear drops. Audiometric tests were performed before
      the operation and up to 3 months following it. RESULTS: All 446 children had a
      normal sensorineural hearing threshold before and after the operation. There was
      no sensorineural hearing loss in the group that was treated with ear drops.
      CONCLUSIONS: Our experience leads us to believe that topical ear drops containing
      ototoxic antibiotics are clinically safe to use for a short period of time.

PMID- 9176805
TI  - Spheno-occipital chondroid chordoma.

PMID- 9176806
TI  - Intracranial sinus thrombosis secondary to ear disease in an adolescent.

PMID- 9176807
TI  - Wegener's granulomatosis masquerading as mastoiditis and lateral-sinus
      thrombosis.

PMID- 9176809
TI  - How I do it: transnasal endoscopic approach to assist in difficult
      adenoidectomies.

PMID- 9176808
TI  - Otitic hydrocephalus.

PMID- 9176810
TI  - The history of otolaryngology in Canada: Laval University.

PMID- 9176811
TI  - Urethane-protected N-carboxyanhydrides (UNCAs) as unique reactants for the study
      of intrinsic racemization tendencies in peptide synthesis.
AB  - We have established that urethane-protected N-carboxyanhydrides (UNCAs) are
      uniquely suited for the study of intrinsic racemization tendencies in peptide
      synthesis. The UNCA allows epimerization only by the direct enolization pathway
      (Proton abstraction from the alpha-carbon) and does not decompose upon
      epimerization. A protocol employing the quantitative separation and analysis of
      enantiomeric N-protected amino acid derivatives by chiral HPLC has been developed
      to measure the intrinsic rate of racemization of UNCAs under widely varying
      reaction conditions. The influence of the tertiary amine structure, UNCA side
      chain structure, and solvent were studied. The same protocol was employed to
      study the intrinsic rate of racemization of N-protected activated amino acid
      intermediates generated via 'onium-type' activating reagents. We have shown that
      the trends influencing the intrinsic rate of racemization of UNCAs are maintained
      under the conditions of in situ activations, and are consistent with the trends
      found in classical studies in the literature. The results are relevant to peptide
      synthesis both in solution and on solid phase. The intrinsic rate of racemization
      for any type of activation with any tertiary amine can be measured by this
      protocol.

PMID- 9176812
TI  - Structure-activity studies of hydrophobic amino acid replacements at positions 9,
      11 and 16 of glucagon.
AB  - We have designed and synthesized eight compounds 2-9 which incorporate neutral,
      hydrophobic amino acid residues in positions 9, 11 and 16 of the glucagon
      molecule: (2) [desHis1, Val9. Ile11,16] glucagon amide, (3) [desHis1, Val9,11,16]
      glucagon amide, (4) [desHis1, Val9, Leu11,16]glucagon amide, (5) [desHis1, Nle9,
      Ile11,16]glucagon amide, (6) [desHis1, Nle9, Val11,16] glucagon amide, (7)
      [desHis1,-Nle9, Leu11,16] glucagon amide, (8) [desHis1, Val9, Leu11,16, Lys17,18,
      Glu21] glucagon amide and (9) [desHis1, Nle9, Leu11,16, Lys17,18, Glu21] glucagon
      amide. The effect of neutral, hydrophobic residues at positions 9, 11 and 16 led
      to good binding to the glucagon receptor. Compared to glucagon (IC50 = 1.5 nM),
      analogues 2-9 were found to have IC50 values of 6.0, 6.0, 11.0, 9.0, 2.5, 2.8,
      6.5 and 7.0 nM, respectively. When these compounds were tested for their ability
      to block adenylate cyclase (AC) activity, they were found to be antagonists
      having no stimulation of adenyl cyclase, with pA2 values of 6.15, 6.20, 6.30,
      7.25, 6.10, 7.30, 6.25 and 7.25, respectively.

PMID- 9176814
TI  - Mycobacterium tuberculosis chaperonin 10 and N-truncated fragments. Their
      synthesis and purification by the isoelectric focusing technique carried out in
      solution.
AB  - The Mycobacterium tuberculosis chaperonin 10 protein and fragments corresponding
      to sequences 59-99, 51-99 and 26-99 were synthesised by the solid-phase
      methodology using a double coupling protocol and without the aid of capping
      agents. After the final acid cleavage using the low TFMSA-high HF protocol the
      polypeptides were purified by either the ion exchange chromatography/RP-HPLC
      combination or the isoelectric separation carried out in solution and followed by
      semi-preparative RP-HPLC. Comparison of the results obtained through the two
      approaches indicated that in general the isoelectricfocusing/HPLC combination was
      superior both in terms of recovery of final material and its purity. The
      advantages found were as follows: (i) Unlike ion exchange chromatography, no
      tailoring of the separation conditions is required, (ii) Several consecutive
      focusings can be carried out in progressively narrower pH gradients. This
      increases the separation resolution without the need of changing other separation
      parameters, (iii) Very little manipulation is needed, and each focusing requires
      3-5h. (iv) Full compatibility with non-ionic denaturants such as 8 M urea. This
      increases solubility so that using the ROTOFOR instrument described here 50-100
      mg crude polypeptide can be processed daily. Thus the isoelectric focusing
      technique carried out in solution is a valid and inexpensive alternative to ion
      exchange chromatography.

PMID- 9176813
TI  - Comparative evaluation of the synthesis and purification of transmembrane peptide
      fragments. Rat bradykinin receptor fragment 64-97 as model.
AB  - The 34-residue peptide CTVAEIYLGNLAGADLILASGLPFWAITIANNFD (TM-34), corresponding
      to the 64-97 sequence of the rat bradykinin, receptor, was selected as a model of
      hydrophobic transmembrane peptide segment for systematic study of synthesis and
      purification strategies. Application of conventional Boc/Bzl chemistry resulted
      in very low yield of the synthesis (around 4%) when DMF was used as the solvent
      for coupling reactions. As shorter resin-bound fragments of TM-34 showed improved
      swelling in 80% NMP/DMSO, the synthesis was repeated in this mixed solvent and
      the yield increased to 12%. A comparative synthesis using optimized Fmoc
      chemistry and Fmoc-(FmocHmb) derivatives of Ala and Leu to prevent aggregation
      did not provide any detectable TM-34. Taken together, these results illustrate
      the synthetic problems associated with hydrophobic sequences, almost regardless
      of the chemistry used. As expected, the hydrophobicity of TM-34 and of most of
      its minor fragments made them scarcely soluble in common solvents. Purification
      could be achieved by loading the crude materials dissolved in 90% AcOH onto a C4
      HPLC column and eluting with a TFA/MeCN linear gradient. CD studies of the TM-34
      and of the shorter fragment with the 74-97 sequence (TM-24) showed a higher
      percentage of alpha-helix structure for the latter. This suggests that the
      shorter sequence may better represent the correct transmembrane region of the
      second helix of the rat bradykinin receptor.

PMID- 9176816
TI  - Circular dichroism studies of human big-endothelin-1 (Big ET-1).
AB  - The circular dischroism (CD) spectra of human endothelin (ET-1) and its precursor
      (Big ET-1) have been compared in order to provide information on the secondary
      structure of Big ET-1. It appears that the secondary structures of the common
      parts of the two molecules are very similar and that the additional C-terminal
      residues in Big ET-1 may contain both helical and sheet components, information
      which may be of use in modeling studies of the Big ET-1 structure. In studies of
      the pH dependence of the conformation of Big ET-1, it was found that Big ET-1
      adopts similar structures at pH 6.0 and 7.0, but has a subtly different
      conformation at pH 8.0 that may result in a reduced susceptibility to proteolysis
      at this pH. This difference may be in the conformation of a turn-type structure,
      producing a less accessible peptide bond in the molecule at the site of cleavage.

PMID- 9176815
TI  - Gastroenteropancreatic effects of xenin in the dog.
AB  - Xenin is a 25 amino acid peptide detected in the gastric mucosa of various
      mammals. It has since been found in low concentrations in other tissues. Xenin
      plasma concentrations increase after meals. The present study reports some
      gastroenteropancreatic effects of this peptide in the dog. Intravenous infusion
      of 64 pmol/kg min synthetic xenin significantly inhibited pentagastrin-stimulated
      gastric acid secretion and stimulated exocrine pancreatic secretion of volume and
      protein. Further, intravenous infusion of xenin in a dose of 1.0 pmol/kg min
      stimulated jejunal motility in the anaesthetized dog. An intravenous infusion of
      32 pmol/kg min xenin raised plasma concentrations of pancreatic polypeptide,
      vasoactive intestinal polypeptide, insulin and glucagon. The present experiments
      therefore indicate manifold bioactive properties of intravenously infused xenin
      in the dog, with jejunal motility the most sensitive target. Conclusions as to
      the physiological role of xenin cannot be drawn from the present experiments. The
      release of other hormonal peptides indicates a complex action of xenin.

PMID- 9176817
TI  - Location of the three disulfide bonds in an antimicrobial peptide from Amaranthus
      caudatus using mass spectrometry.
AB  - The disulfide bridge pairing of Ac-AMP2, a 30-residue peptide isolated from the
      seeds of Amaranthus caudatus, is determined using a fast method involving
      enzymatic fragmentation followed by identification of the fragments with FAB mass
      spectrometry. The results confirm the location of the three disulfide bridges as
      previously established by NMR spectroscopy and molecular modelling.

PMID- 9176818
TI  - Unexpected lability of cysteine acetamidomethyl thiol protecting group. Tyrosine
      ring alkylation and disulfide bond formation upon acidolysis.
AB  - Cleavage and deprotection of the peptidyl resin H-Asn-Gly-Gly-Cys (Acm)
      Glu(OBu(t))-Gln-Tyr(Bu(t))-Cys(Acm)-Ser(Bu(t))-Asp( OBU(t))-[(p-alkoxy)benzyloxy
      polystyrene resin] using standard conditions with various trifluoroacetic acid
      containing mixtures were found to result in partial removal of ordinarily acid
      stable S-Acm groups. Thus, apart from the desired peptide H-Asn-Gly-Gly-Cys (Acm)
      Glu-Gln-Tyr-Cys(Acm)-Ser-Asp-OH, a disulfide-cyclic peptide derivative was also
      isolated. Furthermore, it was found that in another major by-product of the
      peptide resin cleavage the tyrosine side chain had been alkylated with an Acm
      group in a position ortho to the phenolic function. The formation of both by
      products could be suppressed by carrying out the cleavage/deprotection reaction
      at higher dilution and by inclusion of scavengers such as phenol. An authentic
      sample of the disulfide-cyclic peptide was obtained by oxidation of H-Asn-Gly-Gly
      Cys-Glu-Gln-Tyr-Cys-Ser-Asp-OH using Ellman's reagent.

PMID- 9176819
TI  - Palmitate and stearate binding to human serum albumin. Determination of relative
      binding constants.
AB  - Multiple binding equilibria of two apparently insoluble ligands, palmitate and
      stearate, to defatted human serum albumin were studied in a 66 mM sodium
      phosphate buffer (pH 7.4) at 37 degrees C, by determination of dialytic exchange
      rates of ligands among identical equilibrium solutions. The experimental data
      were analysed by a computerised curve fitting procedure using equilibrium
      equations for multiple binding of ligands, containing relative binding constants,
      valid whether the ligands are truly insoluble or are slightly soluble and
      irrespective of aggregation in aqueous solution. A best-fit set of relative
      binding constants was found, and subsequently 30 sets of acceptable constants for
      each set of data in order to evaluate the variation. The data were first fitted
      by the relative Scatchard's equation, then by the relative, stoichiometric
      equation. Scatchard's equation is deduced on the presumption that cooperativity
      is absent while the stoichiometric equation is valid even when cooperativity is
      present. It was found with palmitate as well as with stearate that the two
      equations fitted the data equally well, and it was concluded that the
      observations were compatible with absence of cooperativity. The relative
      Scatchard binding constants were converted to relative, stoichiometric constants
      and it was found that the variations of the latter were slight.

PMID- 9176820
TI  - Peptide synthesis on Sepharose beads.
AB  - NHS-activated Pharmacia HiTrap Sepharose was modified with 1, 3-diaminopropane to
      give an amino-functionalized support suitable for solid-phase peptide synthesis.
      The amide linker p-[(R1S)-alpha-[1-(9H-fluoren-9-yl)-methoxyformamido]- 2, 4
      dimethoxybenzyl]phenoxyacetic acid was incorporated and the acyl carrier protein
      sequence 65-74 was synthesized manually on this support by the Fmoc procedure
      under controlled conditions with monitoring of the coupling reactions. The
      performance of the support in automated multiple synthesis in open reactors, with
      an Abimed AMS 422 according to standard protocols, was evaluated by the synthesis
      of the acyl carrier protein sequence 65-74 and two other 15-mer and 18-mer
      peptides. The quality of the resulting crude peptides was determined by HPLC and
      MALDI-MS, and compared with the same sequences synthesized in parallel on the
      commercial peptide synthesis resin TentaGel S RAM. The modified HiTrap material
      was found to be particularly suited for Fmoc solid-phase peptide synthesis and
      should be advantageous for the utilization of immobilized peptides and peptide
      libraries in biological assays.

PMID- 9176821
TI  - Crystal structures of the even and odd bolaform amino acid derivatives (11-N
      [benzyloxycarbonyl-L-alanyl]aminoundecanoyl)-L-alanyl benzyl ester and (12-N
      [benzyloxycarbonyl-L-alanyl]aminododecanoyl)-L-alanyl benzyl ester.
AB  - Reaction of two alpha, omega-aminocarboxylic acids with N- and C-protected
      alanine leads to bolaform compounds with two secondary amide groups on one end
      and one such group at the other end. Unsymmetric sheet-like structures are formed
      in the crystals. (11-N-[Benzyloxycarbonyl-L-alanyl] aminoundecanoyl)-L-alanyl
      benzyl ester (1) and (12-N-[benzyloxycarbonyl-L-alanyl] aminododecanoyl)-L-alanyl
      benzyl ester (2) form triclinic crystals (spacegroup P1, No.1) with a = 4.917, b
      = 5.614, c = 29.02 A. alpha = 88.40, beta = 93.50, gamma = 100.21 degrees, Z = 1
      (1) and a = 4.954, b = 5.613, c = 30.23 A, alpha = 93.44, beta = 90.07, gamma =
      104.15 degrees, Z = 1 (2). The crystal structures were solved via direct methods
      and refined to R = 0.040 (1) and 0.078 (2) from 2441 and 2725 reflections.

PMID- 9176822
TI  - Infant feeding during the first year of life.

PMID- 9176823
TI  - Galactosemia: promise, frustration and challenge.

PMID- 9176824
TI  - Dietary sodium reduction: is there cause for concern?
AB  - Current dietary guidance includes a recommendation for moderate reduction of
      sodium (Na) intake of US adults to less than 2400 mg (approximately 100 mmol) per
      day. The safety of this recommendation tends to be taken for granted, but
      questions are raised periodically about possible adverse effects. We evaluated
      the evidence available to address these concerns. Relevant sources were
      identified through review of policy documents and a systematic MEDLINE search of
      articles published between 1984 and mid-October 1995. Reviews and commentaries
      were selected to encompass the spectrum of arguments for or against possible
      adverse effects. All identified randomized, human intervention trials of Na
      reduction with at least 6 months' follow up and urinary Na excretion data were
      included; selected additional evidence was evaluated as needed to address
      specific issues. Reports of trials were abstracted to describe relevant design
      features, study populations, level of Na reduction, and comments or data relevant
      to adverse effects. We found that some concerns were based on short-term, Na
      depletion studies and were, therefore, not relevant to moderate Na reduction in
      the population-at-large. Other concerns were largely speculative and, from our
      review, were not supported by the combined evidence from 20 randomized Na
      reduction trials conducted in varied clinical or community settings and involving
      diverse populations followed for up to 5 years. Overall, we identified extensive
      data supporting the safety of public health recommendations for moderate Na
      reduction and none suggesting cause for concern.

PMID- 9176825
TI  - Diet does not ensure normal development in galactosemia.
AB  - This review deals with the treatment of inherited classical galactosemia by a
      lactose-free diet. Although, with dietary treatment, there is a remarkable
      improvement in the acute phase of the disease, the long-term outcome has been
      disappointing for most patients, especially regarding the central nervous system
      and ovarian dysfunction in females. There is a need for new approaches to
      treatment, in combination with diet therapy, that could improve the outcome of
      patients with galactosemia.

PMID- 9176826
TI  - Transitions in infant feeding during the first year of life.
AB  - OBJECTIVE: To document ages at which transitions in infant feeding occur, to
      compare these transitions to literature reports from the 1970s and 80s, and to
      identify maternal characteristics related to the age of the infant when solid
      food was first introduced. METHODS: Ninety-eight mother/infant pairs (middle and
      upper socioeconomic status) participated in the longitudinal study. Using a
      randomized, incomplete block design, in-home interviews were conducted by trained
      personnel when infants were 2, 3, 4, 6, 8, 10, and 12 months of age; each
      mother/infant pair was seen four or five times. Information on food intake,
      including breast milk/formula, was collected at each interview. Means +/- SD and
      frequencies were calculated, and least squares analysis of variance was used to
      develop a predictive model related to the introduction of cereal. RESULTS: Most
      mothers decided on the initial feeding mode (breastfeeding or formula) prior to
      pregnancy; 83% breastfed initially although most (76%) totally discontinued
      breastfeeding by 6 months. Infants' ages varied greatly when each of the seven
      categories of food was introduced, cereal was added to the infants' diets at a
      mean age of 3.8 +/- 1.4 (SD) months, juice 4.7 +/- 2.2, fruit 4.9 +/- 1.6,
      vegetables 5.2 +/- 1.3, mixed foods 7.8 +/- 2.1, table foods 8.2 +/- 2.1, and
      meat 8.2 +/- 2.1. The multivariate model explained 59% of the variability in ages
      of infants when cereal (generally the first solid food) was added. Significant
      variables (p < or = 0.05) were feeding mode, recommendation by the physician, and
      the interaction between feeding mode and education of the mother. Mother's
      employment and sibling rank of the infant contributed to the model (p = 0.06 and
      p = 0.09, respectively). Infants' age when cereal was added was not related to
      the variables of gender or birth weight. CONCLUSIONS: The finding that the
      mothers' decision whether or not to breastfeed was made prior to conception
      supports the importance of population-based education aimed at women in the child
      bearing years as well as patient instruction early in the pregnancy. However, the
      duration of breastfeeding was shorter than was reported in the 1980s. Infants
      varied greatly in ages when the seven categories of complementary foods were
      added to their diets. Although recommendations for delaying introduction of solid
      foods until the infant is 4 to 6 months of age have been in place for more than a
      decade, about half the mothers in this study did so earlier. Characteristics of
      mothers who introduced cereal earliest (i.e., mean age of infants < 4 months)
      were more likely to be formula feeding when cereal was added, to feed cereal via
      the bottle, to be primiparous, to be employed outside the home, and/or not to
      cite the physician as a source for guiding the infant's transition to
      supplemental food.

PMID- 9176827
TI  - Patterns in children's fruit and vegetable consumption by meal and day of the
      week.
AB  - OBJECTIVE: To assess differences in children's consumption of fruit and
      vegetables (F&V) by day of the week and meal of the day. DESIGN: Baseline data
      from two school based nutrition education studies were combined for analysis.
      SUBJECTS/SETTING: 2984 third grade students from 48 participating elementary
      schools in three school districts in the metropolitan Atlanta area. MEASURES OF
      OUTCOME: The frequency of consumption of F&V abstracted by trained registered
      dietitians from prompted 7-day food records. STATISTICAL-ANALYSES PERFORMED:
      Mixed model analysis with meals and days as terms, controlling for the within
      school correlation, gender and ethnic group. RESULTS: F&V were most frequently
      consumed at weekday lunch, and second most frequently at dinner. Participation in
      school lunch accounted for a substantial proportion of F&Vs consumed at lunch.
      Few F&Vs were consumed at breakfast or snack. CONCLUSIONS: School lunch makes an
      important contribution to elementary school students' F&V consumption. Dietary
      change programs should target parents to increase F&V consumption at dinner, and
      target students for the meals over which they assert the most control: breakfast
      and snacks.

PMID- 9176828
TI  - Gastrointestinal tolerance of a pediatric fiber formula in developmentally
      disabled children.
AB  - OBJECTIVE: We performed a masked, randomized, 2-month crossover study with
      developmentally disabled children to study the tolerance of a pediatric adapted
      enteral formula with added soy fiber. METHODS: Twenty children and adolescents
      aged 1 to 17 years, requiring liquid nutrition, were fed Pediasure (PS) and
      Pediasure with approximately 10 g total dietary fiber/l, (PSF10) as their major
      source of energy and nutrient intake for 1 month each. During the two 4-week
      periods of the crossover study, intake, tolerance of the formula, and stool
      characteristics were monitored daily with diaries. Criteria for gastrointestinal
      tolerance were symptoms of emesis, gas, irritability or fussiness. Stool
      characteristics included frequency, consistency, and the need to use elimination
      aids to induce defecation. Following completion of the crossover study, the
      patients were fed PSF10 for an additional 2 months. Anthropometrics were obtained
      at study initiation and at each biweekly visit during the crossover phase and
      monthly during the follow-up phase. Bowel scintigraphy studies were conducted in
      patients with oral or nasogastric intake during the crossover periods.
      Biochemical assessments were conducted at entry, at the end of each crossover
      period, and at exit. RESULTS: There were no differences in any of the tolerance,
      stooling, growth, or biochemical measurements between the feeding regimens, in 11
      children completing this phase of the study. However, there was a trend towards
      using less elimination aids to induce a bowel movement during the fiber
      supplemented formula phase. CONCLUSIONS: Pediasure with fiber is well tolerated
      in children with developmental disabilities.

PMID- 9176829
TI  - Dietary, anthropometric, hematological and biochemical assessment of the
      nutritional status of centenarians and elderly people in Okinawa, Japan.
AB  - OBJECTIVE: The population of old people has increased and nutritional disorders
      are common among them. The assessment of nutritional status and dietary intakes
      of this population is necessary in order to improve their nutritional status and
      reduce risk to infection and mortality. In the present study, data on the
      nutritional status of healthy elderly and centenarians is provided. SUBJECTS:
      Participants were free-living healthy volunteers (39 centenarians; 11 male and 28
      female and 44 elderly in their 70s; 13 male and 31 female). METHODS: Their
      nutritional status was assessed by anthropometric measurements, hematological and
      biochemical variables. Activities of daily living (ADL) of 11 items were scored
      depending upon their activities with a maximum score of 5.0. Dietary survey by
      food recording was done for 2 days and food models were used to obtain the best
      estimate of food intake. Energy and nutrient intakes were compared with Japanese
      recommended dietary allowances (RDAs). RESULTS: The elderly had complete
      independence of physical activities, good sensory function and cognitive
      abilities. The physical activities of male centenarians were between the category
      of completely independent and independent but slow. In female centenarian
      participants, their physical activities were independent but slow or independent
      with difficulty. The functions of auditory acuity and eyesight of the
      centenarians were poor but their cognitive abilities were still good. The elderly
      subjects had short stature whereas their body weight and body mass index (BMI)
      were not low, especially among the women, compelling female elderly to reduce
      their food intake to control the weight. Energy intake of female centenarians was
      low. The ADL in the female centenarians was positively related to energy,
      suggesting that the low energy intake of the female centenarians was mainly due
      to their low ADL. Anthropometric, hematological and biochemical variables of the
      centenarians were lower or near the lower reference limit except serum lipids.
      All the hematological and biochemical variables were statistically lower (p <
      0.05) in the centenarians than in the elderly particularly for females with some
      minor exceptions. CONCLUSION: The results of the present study showed that the
      nutritional status assessed by ADL and anthropometric, hematological and
      biochemical parameters was poor in the centenarian subjects but was maintained in
      the elderly subjects except height and that the diet was not the major factor of
      their problems in the nutritional status.

PMID- 9176830
TI  - Effects of docosahexaenoic acid on serum lipoproteins in patients with combined
      hyperlipidemia: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of daily
      dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the
      absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in
      persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein
      cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL].
      METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week
      single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance
      during the the run-in were randomized into one of three parallel groups (placebo,
      1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered
      in a triglyceride form contained in gelatin capsules. Primary outcome
      measurements were plasma phospholipid DHA content, serum triglycerides, high
      density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA
      content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose
      dependent manner. Significant (p < 0.05) changes were observed in serum
      triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar
      magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL
      C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All
      lipid effects reached an apparent steady state within the first 3 weeks of
      treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein
      cholesterol and triglyceride levels in patients with combined hyperlipidemia. The
      desirable triglyceride and HDL-C changes were present at a dose which did not
      significantly increased non-HDL-C or LDL-C. These preliminary findings suggest
      that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride
      form, may be an effective tool to aid in the management of hypertriglyceridemia.

PMID- 9176831
TI  - Concern regarding bodyweight and energy balance in a group of female university
      students from Madrid: differences with respect to body mass index.
AB  - OBJECTIVE: There are powerful social and psychological motivators that oblige a
      high proportion of women to restrict their energy intake for purely aesthetic
      reasons. The purpose of this research was to assess the relationships between
      concern regarding body weight and energy balance in a group of female university
      students from Madrid, Spain, with respect to differences in body mass index
      (BMI). DESIGN: 126 subjects completed a questionnaire asking if they were happy
      with their body weight, if they considered themselves fat, and if they would like
      to lose some weight. Energy intake was measured by means of a 7-day food record.
      Food intake was recorded by weight, except for that consumed away from home which
      was recorded using traditional household quantities. A comparison of energy
      intake and estimated energy expenditure was performed, using equations proposed
      by the World Health Organization (WHO), to provide a measure of the under- or
      overestimation of intake. RESULTS: All subjects with BMI > or = 25 kg/m2 (6.2% of
      the total) described themselves as fat. 71.4% had, at some time, followed a
      weight-reduction diet. However, even among subjects with BMI < 20 kg/m2 (28.4% of
      the total), 2.9% thought themselves fat and 17.1% had at some time followed a
      slimming diet. This shows excessive concern over losing weight in some women.
      Estimated energy expenditure was similar to energy intake in subjects with BMI <
      20 kg/m2. However, as BMI rose (with a corresponding increase in theoretical
      energy expenditure), the reported energy intake decreased. It is therefore likely
      that underestimation of energy intake increased with BMI (r = 0.4498).
      CONCLUSION: These results indicate that a large percentage of the women studied
      would like to lose weight until they reach, or indeed exceed, the lower limit of
      the acceptable normal range. This could be a danger to their health.
      Underestimation of energy intake was found to increase with BMI, a phenomenon
      that should be kept in mind when designing diet studies.

PMID- 9176832
TI  - Conflicting indicators of biotin status from a cross-sectional study of normal
      pregnancy.
AB  - OBJECTIVE: To assess biotin nutritional status during normal human gestation.
      METHODS: Urine samples were obtained in a cross-sectional design from 16 women in
      early pregnancy (17 +/- 1 weeks, mean +/- 1 SD) and from 13 women in late
      pregnancy (36 +/- 1 weeks). The urinary excretion of biotin, two metabolites
      bisnorbiotin (BNB) and biotin sulfoxide (BSO), and the organic acid 3
      hydroxyisovaleric acid (3-HIA) were measured by HPLC/avidin-binding assay and
      GC/MS, respectively. Excretion rates were expressed as concentration ratios to
      urinary creatinine. RESULTS: In both early and late pregnancy, 3-HIA excretion
      was increased compared to controls (p < 0.0001), suggesting decreased activity of
      a biotin-dependent enzyme caused by tissue biotin depletion. In early pregnancy,
      urinary excretion of biotin was normal; in late pregnancy, excretion was
      increased (p < 0.0002), suggesting biotin status was not decreased. In late
      pregnancy, urinary excretion of BNB and BSO were increased (p < 0.009).
      CONCLUSION: The apparent conflict in the indices of biotin status is not
      explained by this study but could be resolved by two alternate explanations: 1)
      Pregnancy caused an impairment of renal reclamation of biotin, BNB, and BSO
      leading to a paradoxical increase in biotin excretion 2) Pregnancy caused
      metabolic or renal effects that increased 3-HIA excretion nonspecifically; hence,
      the increased 3-HIA excretion did not reflect biotin deficiency. We speculate
      that some of the women studied were marginally biotin deficient and that renal
      wasting and accelerated breakdown of biotin contributed to the deficiency.

PMID- 9176833
TI  - Atherogenesis and the homocysteine-folate-cobalamin triad: do we need
      standardized analyses?
AB  - BACKGROUND: Bioscientists, physicians and nutritionists are newly interested in
      the homocysteine-folate-cobalamin triad, in part because homocysteine may be
      important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be
      an early marker for cobalamin disorders because cobalamin is a cofactor in
      remethylation of homocysteine to methionine. METHODS: In 139 men and 32 women of
      similar mean age of 65 years, we measured markers which have been cited as risk
      for atherosclerosis: serum homocysteine, folate, total cobalamin,
      holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL),
      high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red
      blood cell (RBC) folate, food records and body composition by whole body counting
      of potassium-forty (40K). RESULTS: Statistical relationships among the data
      showed healthy women had lower mean serum homocysteine and their mean RBC folate
      and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower
      than 60 pg/ml (subnormal), yet only 11 of these men and two women had total
      cobalamin < 200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine
      greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum
      homocysteine may be a marker for early cobalamin negative balance. None of the
      subjects in the study had serum folate below abnormal values, i.e., less than 1.6
      mg/ml. All subjects had RBC folate within normal range. Serum homocysteine showed
      inverse relationship with RBC folate and serum total cobalamin, TCI and TCII.
      CONCLUSIONS: 1) importance of using serum holotranscobalamin TCI and TCII as
      markers of cobalamin deficiency, 2) necessity to use documented quantitative
      components of dietary intake if strong comparisons are to be made among
      quantitative values of serum or plasma homocysteine, folate, cobalamin, and
      nutrients in food intake.

PMID- 9176834
TI  - A preliminary report: effects of zinc and micronutrient repletion on growth and
      neuropsychological function of urban Chinese children.
AB  - OBJECTIVE: Zinc is essential for growth and cognition of experimental animals.
      Past research found zinc repletion improved growth of stunted Chinese children.
      Therefore we measured effects of zinc repletion on growth and neuropsychological
      functions of children. DESIGN: Double-blind randomized controlled treatment
      trial. SETTING: Elementary schools in low income districts of Chongqing, Qingdao
      and Shanghai. SUBJECTS: Three hundred-seventy-two 6 to 9 year old first graders.
      INTERVENTIONS: Treatments were 20 mg zinc, 20 mg zinc with micronutrients, or
      micronutrients alone. The micronutrient mixture was based on guidelines of the US
      NAS/NRC. Treatments were assigned to classrooms of 40 or more children each, and
      administered by teachers 6 days per week for 10 weeks. MEASURES OF OUTCOME:
      Changes in knee height and neuropsychological functions. RESULTS: Zinc alone had
      the least effect on growth while zinc with micronutrients had the largest effect;
      micronutrients alone had an intermediate effect. Zinc-containing treatments
      improved neuropsychological functions, but micronutrients alone had little
      effect. CONCLUSIONS: The findings confirm the essentiality of zinc for growth of
      children, and show, for the first time, the essentiality of zinc for
      neuropsychological functions of children. In addition, the need for repletion of
      other potentially limiting nutrients in studies examining the effects of specific
      nutrients on growth and neuropsychological functions was confirmed.

PMID- 9176835
TI  - Lack of toxicity of chromium chloride and chromium picolinate in rats.
AB  - OBJECTIVE: To evaluate the safety of chromium (Cr) as a nutrient supplement.
      Several recent studies have reported beneficial effects of supplemental Cr at
      levels higher than the upper limit of the suggested intake for Cr. Trivalent Cr
      is considered relatively nontoxic but some recent unconfirmed studies have
      questioned its toxicity. We evaluated the toxicity of Cr chloride and a more
      bioavailable form of trivalent Cr, Cr tripicolinate. METHODS: Harlan Sprague
      Dawley rats (4 weeks of age) were fed a stock diet to which was added 0, 5, 25,
      50 or 100 mg of Cr per kg of diet as chloride or picolinate. Fasting blood
      samples were taken at 11 and 17 weeks and animals sacrificed at 24 weeks of age.
      Lack of toxicity was demonstrated by blood and histological measurements.
      Chromium incorporation into tissues was determined by graphite furnace atomic
      absorption. RESULTS: There were no statistically significant differences in body
      weight, organ weights or blood variables among all the groups tested at 11, 17
      and 24 weeks. Blood variables measured were glucose, cholesterol, triglycerides,
      blood urea nitrogen, lactic acid dehydrogenase, transaminases, total protein and
      creatinine. Histological evaluation of the liver and kidney of control and
      animals fed 100 mg/kg Cr as Cr chloride or picolinate also did not show any
      detectable differences. Liver and kidney Cr concentrations increased linearly for
      both the Cr chloride and picolinate fed animals. CONCLUSIONS: These data
      demonstrate a lack of toxicity of trivalent Cr, at levels that are on a per kg
      basis, several thousand times the upper limit of the estimated safe and adequate
      daily dietary intake for humans. Animals consuming the picolinate supplemented
      diets had several-fold higher Cr concentrations in both the liver and kidney than
      those fed Cr chloride.

PMID- 9176836
TI  - Abnormal thyroid function tests in infants with congenital hypothyroidism: the
      influence of soy-based formula.
AB  - OBJECTIVE: To assess the etiology of hyperthyroxinemia or hyperthyrotropinemia in
      infants with congenital hypothyroidism who are on replacement therapy with L
      thyroxine. METHODS: These infants were treated with recommended doses of L
      thyroxine following the diagnosis of congenital hypothyroidism. Because of
      hyperthyroxinemia (2 patients) and hyperthyrotropinemia (1 patient), medication
      compliance and dietary practice (formula type, age of introduction, and
      discontinuation or change of the formula) were assessed. Clinical evaluation was
      also performed. RESULTS: Elevated thyroxine level in 2 infants was associated
      with discontinuation of soy formula 4 weeks previously; reduction of L-thyroxine
      dose normalized serum levels in both of these infants. In the third infant, who
      received soy formula from 1 week of age, TSH remained elevated despite
      incremental L-thyroxine doses of 19 micrograms/kg/day; discontinuation of soy
      formula was followed by normalization of the TSH in 3 weeks and helped attain a
      subsequent decrement of L-thyroxine dose to 8.6 micrograms/kg/day. Neither the
      hyperthyroxinemia nor hyperthyrotropinemia in these infants was associated with
      any adverse behavioral-developmental consequence. CONCLUSION: When initiating soy
      formula feeding in infants with congenital hypothyroidism, the L-thyroxine dose
      should be increased because of significant reduction in intestinal absorption:
      conversely, when soy feeding is discontinued, the L-thyroxine dose should be
      decreased.

PMID- 9176837
TI  - Increased parenteral nutrition calcium and phosphorus for very-low-birth-weight
      infants using computer software assisted ordering.
AB  - BACKGROUND: Providing adequate calcium (Ca) and phosphorus (P) in an appropriate
      ratio to preterm very-low-birth-weight (VLBW: BW < 1500 g) infants receiving
      parenteral nutrition (PN) is difficult because Ca:P solubility in PN is
      relatively low. Computer software assisted ordering (CSAO) was developed to
      integrate PN Ca:P solubility with clinical data to improve parenteral Ca and P
      administration. Our hypothesis was that CSAO would improve the system of
      designing PN by increasing the amount of Ca and P ordered without Ca:P
      precipitation. METHODS: Control PN orders were designed using proprietary
      preprinted PN forms which incorporated predefined PN Ca and P concentrations to
      prevent precipitation, independent of patient Ca or P administration. CSAO
      assessed total daily fluids and correlated parenteral volume with Ca:P solubility
      during order entry to recommend daily Ca and P doses. PN orders which provided >
      or = 80% of total nutrition volume as PN were analyzed. RESULTS: PN was designed
      with more Ca (60.3 +/- 16.7 mg/k/day, mean +/- 1 SD) and P (32.8 +/- 13.9
      mg/k/day) using CSAO compared to control group Ca (50.0 +/- 17.1 mg/k/day) and P
      (25.1 +/- 9.1 mg/k/day), both Ca and P, p < 0.001, CSAO provided > or = 80% of
      the minimum recommended daily Ca in 82% of PN orders compared to 51% of the
      control orders, p < 0.001. No PN mixture demonstrated Ca:P precipitation.
      CONCLUSION: The system of designing PN was improved using computer software
      assisted ordering indicated by increased PN Ca and P content without Ca:P
      precipitation.

PMID- 9176838
TI  - And so spake Goldberger in 1916: pellagra is not infectious!

PMID- 9176839
TI  - Induction of differentiation in cultured rat and human podocytes.
AB  - Mature podocytes are highly differentiated cells that are unable to divide in
      vivo. During glomerulogenesis, podocytes develop from simple cuboidal cells into
      their adult phenotype, which is characterized by a complex pattern of processes.
      Cultivation of podocytes under standard conditions leads to dedifferentiation,
      including the loss of processes and of pp44, a marker of differentiated
      podocytes. In this study, the cell culture conditions for rat and human podocytes
      were modified by avoiding repeated subcultivation. This led to profound
      phenotypic changes in podocytes in vitro. The conversion of cobblestones into
      arborized cells was directly observed, and a series of intermediate phenotypes
      was documented. The cells converted within 3 wk from typical cobblestone
      appearance into individual arborized cells more closely resembling in vivo
      podocytes. Arborized cells were frequently binucleated and reached a size of up
      to 500 microns. Both cobblestone and arborized cells originated from podocytes,
      as evidenced by the expression of a podocyte-specific O-acetylated ganglioside
      and of the WT-1 protein. In contrast to primary cultures and early passages of
      cobblestones, a cloned rat podocyte cell line did not express WT-1 and could not
      be induced to differentiate into arborized cells. This finding indicates a role
      for WT-1 in maintaining differentiation of adult podocytes. The differentiation
      of arborized cells led to growth arrest and was reflected by the formation of
      processes and the expression of pp44 and desmin, which were never detected in
      cobblestones. It was concluded that partial differentiation of cultured podocytes
      can be achieved simply by avoiding repeated subcultivation, resulting in an
      arborized phenotype more closely reflecting in vivo podocytes.

PMID- 9176840
TI  - Mouse glomerular epithelial cells in culture with features of podocytes in vivo
      express aminopeptidase A and angiotensinogen but not other components of the
      renin-angiotensin system.
AB  - The binding of antibodies to podocytic antigens such as the Heymann antigen or
      aminopeptidase A may lead to the induction of a membranous glomerulonephritis in
      several species. To study the possible future interactions of antibodies with
      antigens on these podocytes, epithelial cells from isolated mouse glomeruli were
      cultured. By indirect immunofluorescence, the cells were positive for
      cytokeratin, vimentin, desmin, and the ZO-1 protein, a component of the tight
      junction complex. When rat monoclonal antibodies were used, the cells were also
      positive for the hydrolases aminopeptidase A and dipeptidyl peptidase IV, and
      they stained with ASD-33, a monoclonal antibody that recognized an epitope only
      present on the cell membranes of mouse podocytes. They were negative for the von
      Willebrand factor and did not stain with a monoclonal antibody (ASD-13) that
      binds to endothelial cells of glomeruli and peritubular capillaries. By electron
      microscopy, the cells showed tight junctions but lacked Weibel Palade bodies
      (endothelium), desmosomes, and cilia (parietal epithelium). The mRNA expression
      of several components of the renin-angiotensin system was also examined, and some
      factors indirectly coupled to the renin-angiotensin system component angiotensin
      II in this podocytic culture by RT-PCR analysis. mRNA Expression for the
      angiotensin II degrading hydrolase aminopeptidase A and angiotensinogen was
      found, but this was not found for any other component of this system, such as
      renin, angiotensin-converting enzyme, or the angiotensin II receptors AT1a, AT1b,
      and AT2. Low mRNA expression for dipeptidyl peptidase IV was observed. In
      addition, expression of the growth factors transforming growth factor-beta and
      interleukin-7, and the extracellular matrix components fibronectin, laminin B2,
      perlecan, and collagen IV alpha 1, was observed. Given these characteristics, a
      glomerular epithelial cell culture with features of podocytes in vivo that will
      allow future studies on the interaction of anti-aminopeptidase A monoclonal
      antibodies and angiotensin II with aminopeptidase A was established. This is of
      interest in light of the observation that injection of mice with anti
      aminopeptidase A antibodies causes an acute albuminuria.

PMID- 9176841
TI  - Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.
AB  - Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent
      feature of some types of glomerulonephritis, including lupus nephritis. The
      mechanism(s) underlying monocyte influx into the kidney is not fully understood.
      Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a
      chemotactic factor involved in the recruitment of monocytes/macrophages in the
      glomeruli of rats with mesangioproliferative as well as anti-glomerular basement
      membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA
      expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of
      genetically determined immune complex disease that mimics systemic lupus in
      humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1
      transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had
      not yet developed proteinuria nor renal damage. Message levels, which increased
      markedly with the progression of nephritis and in association with mononuclear
      cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2
      month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was
      demonstrated in glomeruli and, even more striking, in tubular epithelial cells.
      Western blot analysis demonstrated increased expression of MCP-1 protein in
      kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W
      mice were treated with cyclophosphamide up to 12 months of age, expression of MCP
      1 in the renal tissue remained low, the influx of inflammatory cells did not
      appear, and glomerular and tubular structures remained well preserved. These data
      suggest that elevated MCP-1 might act as a signal for inflammatory cells to
      infiltrate the kidney in lupus nephritis.

PMID- 9176843
TI  - Severe uremia depresses the ability of perifused rat pituitary cells to secrete
      growth hormone in response to growth hormone releasing hormone.
AB  - To examine whether growth hormone (GH) secretion is impaired by chronic renal
      failure (CRF) and to gain some insight into the influence of uremia itself and
      associated malnutrition, the GH secretory response of dispersed anterior
      pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in
      5/6 nephrectomized (UREM, N = 15) and three groups (N = 15 each) of normal renal
      function, sham-operated rats under three different nutritional conditions: fed
      "ad libitum" (SAL), pair-fed with a diet similar to the UREM group (SPF), and
      pair-fed with a diet similar to the UREM group in terms of protein ingestion but
      calorically supplemented up to intake of SAL group (SPF+). Ten days after
      nephrectomy, UREM rats had severe CRF, as shown by much higher (P < 0.0001) serum
      urea nitrogen concentrations (X +/- mean +/- SE) than sham groups (59 +/- 6
      versus 8 +/- 0, 9 +/- 0, and 5 +/- 0 mmol/L, respectively), and they were growth
      retarded, as shown by lower gains (P < 0.0001) in weight (13.5 +/- 2.5 versus 62
      +/- 2.1, 20.5 +/- 1.9, and 50.4 +/- 1.0 g) and length (2.9 +/- 0.2 versus 5.8 +/-
      0.1, 3.6 +/- 0.1, and 5.6 +/- 0.1 cm). Perifusion studies showed similar basal GH
      secretory rate (ng/min/10(7) cells) in the four groups. A fixed sequence of
      progressively increasing GHRH doses resulted in a lower overall mean GH secretion
      in UREM rats (15.8 +/- 1.6 ng/min/10(7) cells), as compared with SAL (50.8 +/-
      9.0 ng/min/10(7) cells, P < 0.01), SPF (33.0 +/- 3.3 ng/min/10(7) cells, P <
      0.05), and SPF+ (49.4 +/- 5.1 ng/min/10(7) cells, P < 0.01) groups. Analysis of
      dose-response curves showed that the maximal secretory response was produced by
      the same concentration of GHRH (10 nM) in the four groups and was lower (P <
      0.01) in UREM than SAL and SPF+ rats (34.9 +/- 5.0 versus 115.7 +/- 28.4 and 98.9
      +/- 9.8 ng/min/10(7) cells). The concentration of GHRH that caused the half of
      maximal effect was identical, close to 1 nM, in the four groups of animals. This
      study provides direct evidence that the ability of pituitary cells to secrete GH
      in response to GHRH is depressed in severe CRF. The lower secretory capacity of
      pituitary gland is only partly dependent on caloric malnutrition associated with
      CRF. Data of dose-response curves suggest that decreased GH secretion may be
      related to a lesser number of pituitary receptors for GHRH.

PMID- 9176842
TI  - Involvement of IL-4 in human glomerulonephritis: an in situ hybridization study
      of IL-4 mRNA and IL-4 receptor mRNA.
AB  - Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of
      glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in
      human kidney has not been fully determined. Nonradioactive in situ hybridization
      was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from
      normal kidneys and specimens from a variety of human kidney diseases. In normal
      glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly
      expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were
      strongly expressed in resident glomerular cells, including mesangial cells,
      glomerular epithelial cells, and cells of the Bowman's capsule. The relationship
      between the expression of these mRNA and the degree of glomerular injury was
      different in different types of glomerulonephritis. In IgA nephropathy and non
      IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated
      positively with the degree of mesangial hypercellularity and extracellular matrix
      expansion. However, IL-4R expression was relatively constant. In contrast, the
      expression of IL-4 and IL-4R mRNA correlated negatively with the degree of
      glomerular injury in lupus nephritis. Coexpression and discordant expression of
      these mRNA forms were observed in individual cells. In tubulointerstitium with
      severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and
      some of the infiltrating cells and fibroblasts. The interstitial expression of
      these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative
      glomerulonephritis, and lupus nephritis and correlated positively with the degree
      of tubulo-interstitial changes. These results suggest that an autocrine and/or
      paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may
      be involved in tissue injury in glomerulonephritis.

PMID- 9176844
TI  - Renal responses to sodium restriction in patients with early diabetes mellitus.
AB  - Increased GFR and decreased renal vascular resistance are common renal
      hemodynamic changes in persons with early, uncomplicated, insulin-dependent
      diabetes mellitus. It has been hypothesized that excess total-body sodium in
      patients with diabetes contributes to the renal vasodilation, possibly by
      suppressing vasoconstricting neurohormonal systems. This study was undertaken to
      examine whether sodium restriction could normalize these renal abnormalities.
      Subjects were 12 male patients with uncomplicated insulin-dependent diabetes
      mellitus (duration, < 5 yr). Results were compared with those of an age- and
      gender-matched control group. All subjects received either a high-sodium diet
      (200 mmol/day) or a sodium-restricted diet (20 mmol/day) for 7 days, according to
      a randomized crossover protocol. GFR and RPF were measured using inulin and para
      aminohippurate clearance techniques, respectively. Subjects with diabetes were
      maintained euglycemic during the clearance measurements. GFR was significantly
      higher in the diabetic group than in the control group with sodium repletion (124
      +/- 4 versus 107 +/- 8 mL/min/1.73 m2; P = 0.03), and renal vascular resistance
      was significantly reduced (94 +/- 6 versus 107 +/- 17 mm Hg/L/min; P = 0.05). In
      response to sodium restriction, the hematocrit increased significantly in both
      groups, as did PRA and aldosterone, although responses in the diabetic group were
      somewhat blunted, indicating persisting volume expansion. Despite this humoral
      activation, sodium restriction had little effect on renal hemodynamic function in
      control subjects. In the diabetic subjects, this maneuver appeared to exacerbate
      the underlying renal abnormalities, with the GFR increasing to 131 +/- 4
      mL/min/1.73 m2 (P = 0.05) and the renal vascular resistance declining to 73 +/- 5
      mm Hg/L/min (P = 0.001). These data indicate that, rather than correcting renal
      hyperperfusion, sodium restriction exacerbates these characteristic
      abnormalities, suggesting that mechanisms other than suppression of
      vasoconstrictor activity are operative in the underlying renal hemodynamic
      abnormalities of early, uncomplicated, insulin-dependent diabetes mellitus.

PMID- 9176845
TI  - Quinapril decreases renal endothelin-1 expression and synthesis in a normotensive
      model of immune-complex nephritis.
AB  - Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the
      progression to renal failure in several experimental models of renal injury.
      Endothelin-1 (ET-1) possesses potent biological actions on renal vessels and has
      been considered as a potential mediator of renal damage. Because angiotensin II
      (Ang II) induces ET-1 synthesis in endothelial and mesangial cells, we
      hypothesized that some of the beneficial effects of the ACE inhibitors could
      result from the blockade of ET-1 synthesis. In a normotensive model of immune
      complex nephritis, in which there exists an increase in renal ACE activity, the
      effect of the ACE inhibitor quinapril on preproET-1 and ETA receptor mRNA
      expression, as well as on ET-1 protein levels, was examined in this study. In
      relation to controls, nephritic rats showed an increase in preproET-1 and ETA
      receptor gene expression in renal cortex and medulla, coinciding with the maximal
      renal ACE activity. PreproET-1 mRNA (in situ hybridization) and ET-1 protein
      (immunohistochemistry) were localized in glomerular capillary walls, mesangial
      and glomerular epithelial cells, as well as in the brush border of some proximal
      tubules, and in small vessels. In nephritic rats, there was an increase in
      preproET-1 mRNA levels and ET-1 protein in all of these areas, without
      modification of their distribution. The administration of the ACE inhibitor
      quinapril decreased proteinuria and morphological lesions, preproET-1 gene
      transcription, and ET-1 protein levels, as well as the ETA receptor mRNA. The
      results from this study show that in a normotensive model of immune-complex
      nephritis, there was an overexpression of ET-1 in several structures of the
      kidney that was downregulated by quinapril administration. The beneficial effect
      of ACE inhibitors could be a result of the modulation of local production of Ang
      II and ET-1.

PMID- 9176846
TI  - Prognostic significance of the early course of minimal change nephrotic syndrome:
      report of the International Study of Kidney Disease in Children.
AB  - The ability to predict the course in children with newly diagnosed minimal change
      nephrotic syndrome (MCNS) may have significant therapeutic implications. Previous
      attempts based on data available at disease onset have not been successful.
      Therefore, it was investigated whether characterization of the initial response
      to adrenocortical steroids and the course during the early months of disease are
      predictive of the subsequent outcome. Three hundred-eighty-nine children with
      MCNS, diagnosed at onset, were treated with standard prednisone regimens and
      monitored for up to 17 yr (mean, 9.4 yr). They were classified, after 8 wk of
      therapy, as initial responders (complete remission) or initial nonresponders
      (continued proteinuria). Subsequent classifications included nonrelapsers,
      infrequent relapsers, and frequent relapsers. At 8 yr of follow-up, 80% of
      patients were in remission. Three-fourths of initial responders who remained in
      remission during the first 6-month period after initial therapy (nonrelapsers;
      40% of the entire series) either continued in remission during their entire
      course or relapsed rarely. In contrast, initial relapsers, both frequent and
      infrequent, achieved a nonrelapsing course only after an average of 3 yr.
      Unremitting proteinuria during the initial 8 wk of treatment was followed by
      progression to ESRD in 21%. When proteinuria during the initial 8 wk continued
      through the subsequent 6 months, progression to renal failure occurred for 35%.
      Although 95% of children with MCNS do well, 4 to 5% die from complications or
      undergo progression to ESRD. Documentation of the early course aids in
      identifying those at increased risk for a poor outcome. More aggressive therapy
      may be indicated for these individuals.

PMID- 9176847
TI  - Protein intake in renal disease.
AB  - The dietary protein intake (DPI) of 766 patients (aged 7 to 88 yr) was determined
      from 24-h urinary urea and protein excretion by urea kinetic modelling. Five
      hundred sixty-five patients had a normal serum creatinine concentration, and of
      these 565, 385 patients had no dietary modification advised and 180 were advised
      to follow a low-protein diet. The remaining 201 patients had an increased serum
      creatinine concentration; 148 of these 201 patients had been advised to restrict
      their DPI. Patients with a normal serum creatinine concentration who had no
      dietary restriction had a significantly higher DPI than those advised to restrict
      their protein intake (1.08 +/- 0.01 versus 0.96 +/- 0.02 g/kg per day (mean +/-
      SEM), P < 0.01). Similarly, patients with abnormal renal function who were
      advised to follow a low-protein diet had a reduced DPI (0.93 +/- 0.01 versus 0.87
      +/- 0.02 g/kg per day; P < 0.05). A lower DPI correlated with level of renal
      dysfunction, independent of dietary advice (P < 0.0001). In the overall
      population, DPI correlated with body mass index (BMI; P < 0.0001) and serum
      albumin (P < 0.0001), and inverse correlations were evident between age (P <
      0.0001), blood glucose level (P < 0.01), serum cholesterol level (P < 0.0001),
      and triglyceride levels (P < 0.0001) independently of renal function. Fifty-two
      patients were assessed within the 3 months before the commencement of dialysis,
      and 47 were reassessed within 3 months after the commencement of dialysis.
      Despite advice regarding an increase in dietary protein after the commencement of
      dialysis, this increase failed to occur within the 3 months of commencement of
      dialytic therapy (0.79 +/- 0.04 versus 0.82 +/- 0.03 g/kg per day); P = 0.64).
      However, 6 to 9 months after the commencement of dialysis, a significant increase
      in protein intake was evident (1.04 +/- 0.04 g/kg per day; P < 0.005 versus both
      prior measurements). Hence a low DPI in renal impairment occurs independently of
      dietary advice, but compliance with such advice is evident because patients
      advised to consume a low-protein diet had significantly lower protein intake than
      did patients receiving no dietary advice. Adaptation to a high-protein diet after
      instigation of dialysis is unsuccessful in the short term, irrespective of
      whether or not advice is given regarding a low-protein diet before dialysis is
      initiated. However, 6 to 9 months after the commencement of dialysis, a
      significant increase in protein intake occurs, which in the hemodialysis
      population correlates with dialysis delivery.

PMID- 9176848
TI  - Effect of an acute oral protein load on renal acidification in healthy humans and
      in patients with chronic renal failure.
AB  - The effect of a meat load on the renal handling of acid-base balance was studied
      in ten healthy subjects (GFR by inulin clearance = 98.5 +/- 8.14 ml.min-1.1.73 m
      2) and in ten patients affected by chronic renal failure (CRF) (GFR = 39.9 +/-
      5.3 ml.min-1.1.73 m-2). After the meat load (2 g.kg-1 body weight of cooked
      unsalted red meat), GFR increased by 26.9% (peak value) over baseline in healthy
      subjects and by 32% in CRF patients. The acid-base status of the healthy subjects
      was in the normal range, whereas the CRF patients disclosed a slight metabolic
      acidosis. After a meat load, there was, in the healthy subjects, an increase in
      the filtered load of bicarbonate coupled to an enhanced tubular reabsorption and
      urinary excretion. The time course between bicarbonate load and urinary excretion
      was coincident. In CRF patients, the increase of bicarbonate tubular load after
      the meal was associated with an increase in tubular reabsorption but not in
      urinary excretion of this anion. The relationship between bicarbonate load and
      reabsorption was linear in both groups up to the highest filtered loads. Baseline
      titratable acidity (TA) and ammonium (NH4+) excretion (expressed per ml GFR) were
      increased in CRF patients as compared with control subjects, but no changes were
      found after the meat load in both groups in these experimental conditions. The
      data indicate that the renal tubules contribute to the maintenance of acid-base
      balance both in healthy subjects and in CRF patients by reabsorbing most of the
      additional bicarbonate load. The transient, but significant, increase in
      bicarbonate excretion observed in healthy subjects could be related to the
      increased tubular load of bicarbonate. In CRF patients, tubular bicarbonate
      reabsorption was more complete, possibly because of the stimulation of H+
      secretion by the mild metabolic acidosis. TA and NH4+ did not participate in
      tubular compensation of the increased buffer load.

PMID- 9176849
TI  - Contrasting effects of calcium channel blockade versus converting enzyme
      inhibition on proteinuria in African Americans with non-insulin-dependent
      diabetes mellitus and nephropathy.
AB  - Hypertension is a common finding in non-insulin-dependent diabetes mellitus
      (NIDDM) nephropathy. African Americans have a high prevalence of NIDDM and
      hypertension, and are relatively resistant to the antihypertensive effects of
      converting enzyme inhibitors (CEI) but respond well to calcium channel blockers
      (CCB). In the long-term study presented here, the effects of isradipine, a
      dihydropyridine calcium antagonist, on the course of the nephropathy were
      investigated and compared with the effects of captopril in 31 African Americans
      with NIDDM and proteinuria (> or = 500 mg/day). The patients were stratified by
      levels of GFR and proteinuria, and they were randomized to receive isradipine (N
      = 16) or captopril (N = 15); doses were adjusted to maintain similar BP levels (<
      140/90). At 6 months, mean arterial pressure was similar (102 +/- 3 and 104 +/- 3
      mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged
      (delta = -4 +/- 3 and +1 +/- 3 ml/min/1.73 in the isradipine and captopril
      groups, respectively; P = NS). However, proteinuria in the isradipine group
      increased by approximately 50% (2.01 +/- 0.40 versus 3.04 +/- 0.70 mg/mg
      creatinine at baseline versus 6 months, respectively, P < 0.05), whereas
      captopril reduced proteinuria by 30% after 6 months (2.85 +/- 0.70 at baseline
      versus 2.30 +/- 0.70 mg/mg creatinine, P < 0.05). Dietary protein, sodium intake,
      and HbA1C levels were similar in both groups and did not differ from baseline. It
      was concluded that over 6 months, captopril reduces and isradipine increases
      proteinuria in African Americans with NIDDM and nephropathy. Whether this
      contrasting effect on proteinuria will result in different rates of progression
      is not known, but dihydropyridine CCB should be used cautiously in African
      Americans with diabetic nephropathy.

PMID- 9176850
TI  - Studies on platelet membrane glycoproteins and platelet function during
      hemodialysis.
AB  - Hemodialysis only partially corrects the defects in platelet function associated
      with uremia. Platelet contact with the artificial surfaces of the dialysis filter
      during hemodialysis can itself cause platelet activation, degranulation, and loss
      of platelet membrane glycoproteins. Although the transient platelet dysfunction
      that occurs after platelet contact with foreign surfaces during cardiopulmonary
      bypass has been well characterized, there has been no such investigation of
      hemodialysis. In this study of hemodialysis patients, bleeding times (BT) and the
      response of their platelets to thrombin, ristocetin, and collagen were measured
      before, immediately after, and in some patients, the day after hemodialysis. In
      addition, membrane glycoproteins in platelets obtained at these time intervals
      were studied using fluorescein isothiocyanate (FITC) conjugated monoclonal
      antibodies (mAb) CD42b (anti-GPIb), CD41a (anti-GPIIb/IIIa), and CD62 (anti-P
      selectin), with flow cytometry. BT was significantly prolonged, and response to
      thrombin and ristocetin was significantly decreased immediately after
      hemodialysis (P < 0.01). Binding of CD42b mAb to the platelet membrane was
      decreased in platelets obtained immediately after hemodialysis. Most patients had
      shortened BT and demonstrated increased response of their platelets to thrombin
      and increased CD42b binding to their platelets the day after hemodialysis. These
      findings suggest that in uremic patients, hemodialysis is associated with
      transient platelet dysfunction and decreased membrane expression of GPIb.

PMID- 9176851
TI  - Extracorporeal therapy requirements for patients with acute renal failure.
AB  - Renal replacement therapy (RRT) requirements for critically ill patients with
      acute renal failure (ARF) depend on numerous factors, including the degree of
      hypercatabolism, patient size, and desired level of metabolic control. However,
      the current practice at many institutions is to prescribe generally similar
      amounts of RRT to ARF patients essentially without regard for the above factors.
      In this study, a computer-based model designed to permit individualized RRT
      prescription to ARF patients was developed. The critical input parameter is the
      desired level of metabolic control, which is the time-averaged BUN (BUNa) or
      steady-state BUN (BUNs) for intermittent hemodialysis (IHD) or continuous RRT
      (CRRT), respectively. The basis for the model was a group of 20 patients who
      received uninterrupted CRRT for at least 5 days. In these patients, the
      normalized protein catabolic rate (nPCR) increased linearly (r = 0.974) from 1.55
      +/- 0.14 g/kg per day (mean +/- SEM) on day 1 to 1.95 +/- 0.15 g/kg per day on
      day 6. The daily urea generation rate (G), determined from the above linear
      relationship, was utilized to produce BUN versus time curves by the direct
      quantification method for simulated patients of varying dry weights (50 to 100
      kg) who received variable CRRT urea clearances (500 to 2000 ml/h). Steady-state
      BUN versus time profiles for the same simulated patient population treated with
      IHD regimens (K = 180 ml/min, T = 4 h) of variable frequency were generated by
      use of a variable-volume, single-pool kinetic model. From these profiles,
      regression lines of required IHD frequency (per week) versus patient weight for
      desired BUNa values of 60, 80, and 100 mg/dl were obtained. Regression lines of
      required CRRT urea K (ml/h) versus patient weight for desired BUNs values of 60,
      80, and 100 mg/dl were also generated. For the attainment of intensive IHD
      metabolic control (BUNa = 60 mg/dl) at steady state, a required treatment
      frequency of 4.4 dialyses per week is predicted for a 50-kg patient. However, the
      model predicts that the same degree of metabolic control cannot be achieved even
      with daily IHD therapy in patients > or = 90 kg. On the other hand, for the
      attainment of intensive CRRT metabolic control (BUNs = 60 mg/dl), required urea
      clearance rates of approximately 900 ml/h and 1900 ml/h are predicted for 50- and
      100-kg patients, respectively. This model suggests that, for many patients,
      rigorous azotemia control equivalent to that readily attainable with most CRRT
      can only be achieved with intensive IHD regimens. Following prospective clinical
      validation, this methodology may be a useful RRT prescription tool for critically
      ill ARF patients.

PMID- 9176852
TI  - Determinants of intrarenal Doppler indices in stable renal allografts.
AB  - Color Doppler sonography has been introduced for graft monitoring after renal
      transplantation. Little is known, however, about independent factors that have an
      impact on intrarenal Doppler indices as indicators for transplant dysfunction.
      Therefore, in this study, potential determinants of the resistive index (RI) and
      of the pulsatility index (PI) in 110 patients with stable renal allografts were
      studied. The mean RI and PI were 0.70 +/- 0.07 (range, 0.53 to 0.88) and 1.36 +/-
      0.21 (range, 0.91 to 1.98), respectively. In multivariate regression analysis, RI
      and PI correlated significantly with age and arterial pulse pressure of the
      recipient. There was no correlation with donor age, heart rate, mean arterial
      blood pressure, and cyclosporine trough levels. Furthermore, parameters of kidney
      function, such as serum creatinine concentration, creatinine clearance rate, 51Cr
      ethylenediaminetetraacetate clearance rate, and proteinuria, showed no
      significant correlation with the Doppler indices. The data indicate that
      intrarenal Doppler indices of the grafts are hemodynamic indices, primarily
      depending on the recipient-related vascular compliance rather than on the
      function of the graft. Therefore, only intraindividual comparison of the Doppler
      indices may be useful to detect potential changes of graft resistance during long
      term follow-up.

PMID- 9176853
TI  - Expression of PDGF and PDGF receptor mRNA in glomeruli in IgA nephropathy.
AB  - This study investigated the mRNA expression of the platelet-derived growth factor
      (PDGF) A-chain and B-chain and PDGF-beta receptor in glomeruli of 15
      immunoglobulin A (IgA) nephropathy kidneys and those with minimal-change lesion
      (N = 7), membranous nephropathy (N = 3), and focal segmental glomerulonephritis
      (N = 5), by using competitive RT-PCR methods. The level of PDGF B-chain and beta
      receptor mRNA expression in IgA nephropathy was significantly higher than in the
      other forms of glomerulonephritis, but mRNA expressions of PDGF A-chain were not
      significantly different. Significant correlations were observed between the
      urinary protein level and the mRNA level of PDGF-beta receptor expression and
      PDGF B-chain expression, and between the serum creatinine level and the mRNA
      level of PDGF-beta receptor expression. The PDGF B-chain and beta-receptor may be
      upregulated and accelerate cell proliferation in a paracrine or autocrine manner
      and may play a role in the pathogenesis of IgA nephropathy.

PMID- 9176854
TI  - Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with
      lipoprotein glomerulopathy.
AB  - Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria,
      lipoprotein thrombi in the glomeruli, and increased concentration of plasma
      apolipoprotein (apo) E. It is believed that a genetic disorder of apo E may be
      present and associated with the disease. Three patients with LPG were examined in
      this study. The patients' DNA sequences were analyzed, and a nucleotide G to C
      point mutation in exon 4 of the apo E gene was confirmed in each patient. This
      missense mutation denotes amino acid substitution of the proline residue for
      arginine residue at position 145 of apo E. This variant (apo E Sendai) may cause
      a marked molecular conformational change of the apo E. These findings suggest
      that a novel variant is etiologically related to LPG.

PMID- 9176855
TI  - Treatment of the idiopathic nephrotic syndrome: regimens and outcomes in children
      and adults.
AB  - This review compares the biopsy patterns, complications, responses to therapy,
      and long-term outcomes of idiopathic NS in children and adults. On first
      examination, distinctions between the pediatric and adult diseases seem more
      quantitative than absolute. However, underlying determinants of outcome,
      including immunocompetence, growth, maturity, and senescence, can present very
      different challenges for pediatricians and internists. The major biopsy patterns
      in pediatric NS include MCD, FSGS, and DMP. MCD is overwhelmingly the most
      frequent and most steroid-responsive of the three but commonly presents problems
      of massive edema, serious bacterial infections, and multiple relapses. Because of
      the prompt response of pediatric MCD to corticosteroids, steroid resistance in
      children has generally been defined as persistence of proteinuria after 1 month
      of daily followed by 1 month of intermittent prednisone administration. By this
      criterion, nephrotic FSGS is usually steroid-resistant and, if not controlled by
      more aggressive therapy, typically progresses to ESRD. DMP is commonly steroid
      resistant but may slowly resolve. It is not clear to what extent remissions of
      DMP represent a delayed response to steroids or would have occurred without
      treatment. Biopsies showing a few globally obsolescent glomeruli or mild
      mesangial hypercellularity may be associated with greater difficulty in
      management but have been included in the broad category of MCD. Moreover,
      evolution of patterns in serial biopsies, variable steroid-responsiveness of FSGS
      and DMP, and progression of some cases of MCD to ESRD suggest common features in
      the three major categories. Among adults with idiopathic NS, FSGS is the most
      frequent biopsy pattern, followed by MN (which is rare in children) and then by
      MCD. In contrast to its pediatric counterpart, MCD in adults is less regularly
      and more slowly responsive to corticosteroids and in the elderly is more commonly
      associated with hypertension and renal failure. MCD in adults is less likely to
      relapse once remission is achieved. Adults with FSGS present less commonly with
      severe edema than do children with this lesion. Although children and adults with
      FSGS present similar challenges of resistance to therapy and loss of renal
      function, the more aggressive oral steroid regimens used by internists preclude
      strict comparisons between pediatric and adult series. There is insufficient
      information to support a systematic analysis of DMP in adults. Cytotoxic agents
      and cyclosporine have been used with varying success in children and adults with
      difficult cases of NS. In MCD, an alkylating agent can increase the likelihood
      and duration of remission. Cyclosporine can also improve control in MCD, but
      continued treatment is often needed to maintain remission. Significant control of
      steroid-resistant FSGS has not been achieved with limited courses of an
      alkylating agent or cyclosporine. Longer courses of either of these
      immunosuppressants, especially when combined with intermittent steroid
      administration, can produce more complete and/or more sustained remissions.
      However, cyclosporine nephrotoxicity is more severe in FSGS than in MCD and in
      steroid-resistant than in steroid-dependent NS, regardless of biopsy pattern. A
      protocol combining iv M-P pulses, alternate-day prednisone, and an alkylating
      agent in steroid-resistant pediatric FSGS has produced the highest percentage of
      sustained remissions with normal renal function, of all reported regimens.
      Controlled trials of this and other combined drug protocols are needed in
      children and adults.

PMID- 9176857
TI  - The Nephrology Manpower Study: what does it mean and what do we do now?

PMID- 9176856
TI  - Lipoprotein glomerulopathy: a new role for apolipoprotein E?

PMID- 9176858
TI  - Estimating workforce and training requirements for nephrologists through the year
      2010: pediatric perspectives.

PMID- 9176859
TI  - Nephrotic syndrome, renal failure, and renal malignancy: an unusual tumor
      associated glomerulonephritis.
AB  - The association between malignancy and glomerular disease has been appreciated
      for over three decades. Although the relationship between membranous
      glomerulonephritis or minimal-change nephrotic syndrome and carcinoma or
      lymphoma, respectively, are the most widely known, several other glomerular
      lesions have been described in patients with malignancy. In this article, a
      patient who presented with nephrotic syndrome, volume overload, and renal
      failure, who was subsequently found to have a renal mass, is described. Resection
      of the mass, which proved to be a renal cell carcinoma, led to resolution of
      proteinuria and improvement of renal function. Pathology on the noninvolved
      portion of the kidney revealed a membranoproliferative glomerular lesion, a
      lesion usually associated with lymphomas and not previously described with renal
      carcinoma. Although a role of tumor antigens and anti-tumor antibodies in
      producing glomerular immune deposits has been speculated upon, the evidence for
      this assertion was spotty. However, reports of remission of proteinuria after
      tumor treatment or removal support a role of tumor products in pathogenesis.
      Although the association between proteinuria and malignancy is rare, it should be
      kept in mind, particularly in older patients with membranous glomerulonephritis
      where the possibility of malignancy needs to be further evaluated.

PMID- 9176860
TI  - Acidosis and coma after hemodialysis.
AB  - Ethylene glycol poisoning is a rare yet potentially fatal illness seen most
      commonly in association with ingestion by alcoholics or in suicide attempts. It
      is characterized by an elevated anion gap metabolic acidosis, osmolal gap,
      calcium oxalate crystals in the urine, and a well-defined clinical picture.
      Prompt treatment is crucial because effective intervention can prevent the
      neurologic, cardiac, pulmonary, and renal sequelae associated with ethylene
      glycol poisoning. Hemodialysis offers rapid clearance of ethylene glycol and its
      toxic metabolites. In this article, the case of a hemodialysis patient who
      suffered contamination of the dialysate solution with ethylene glycol, leading to
      altered mental status, coma, and severe anion gap metabolic acidosis, is
      reported. Despite prolonged dialysis and correction of the acidosis, the patient
      remained comatose and subsequently died.

PMID- 9176861
TI  - The Ad Hoc Committee report on estimating the future workforce and training
      requirements for nephrology. The Ad Hoc Committee on Nephrology Manpower Needs.

PMID- 9176862
TI  - Future workforce needs for pediatric nephrology: an analysis of the nephrology
      workforce and training requirements by the Workforce Committee of the American
      Society of Pediatric Nephrology.

PMID- 9176863
TI  - Analysis of the possible protective role of metallothionein in streptozotocin
      induced diabetes using metallothionein-null mice.
AB  - In order to clarify a possible protective role of metallothionein (MT) in the
      development of streptozotocin (STZ)-caused insulin-dependent diabetes mellitus
      (IDDM) and its mechanisms, we studied whether MT is effective for protection
      against STZ-caused IDDM by utilizing MT-null (isoforms MT-I and II) transgenic
      mice. It was found that Zn pretreatment (I mg/kg body weight as ZnSO4) has a
      unique inhibitory effect on IDDM development in MT-null mice in contrast to no
      marked effect in control (C57BL/6J) mice, suggesting that Zn ions free from MT
      molecules exerted this protective effect. The highest Zn dose (10 mg/kg body
      weight) fully suppressed development of hyperglycaemia in both types of mice.
      Pretreatment with Zn partially led to recovery of superoxide dismutase activities
      in the liver and pancreas in which STZ administration suppressed superoxide
      dismutase activity in both types of mice. The present study suggests that Zn
      plays an important role in the pathogenesis of IDDM, although a possible
      involvement of MT in the protection of STZ-caused IDDM cannot be completely
      negated.

PMID- 9176864
TI  - Cadmium-induced lipid peroxidation and the antioxidant system in rat
      erythrocytes: the role of antioxidants.
AB  - Cadmium (Cd)-induced oxidative damage in erythrocytes causes loss of membrane
      function by enhancing lipid peroxidation (LPO) and altering the erythrocyte
      antioxidant system. Vitamin E and/or selenium (Se) was administered to rats,
      prior to Cd intoxication, in order to prepare the animals to withstand oxidative
      assault. The treatment with Cd increased LPO in erythrocytes while animals
      pretreated with vitamin E and/or Se prior to Cd treatment showed decreased LPO as
      compared with animals given Cd alone. The erythrocyte SOD and CAT activities
      decreased significantly with Cd treatment. The pretreatment with vitamin E and/or
      Se prior to Cd administration partially reversed such changes. The erythrocytes
      showed a marked depletion in glutathione (GSH) content with Cd treatment. The
      antioxidant treatments before Cd administration helped to maintain the
      erythrocyte GSH content. The erythrocyte glutathione reductase (GSH-R) activity
      increased markedly when treatments with vitamin E and Se were applied. The GSH-R
      activity was not observed to decrease in animals treated with antioxidant prior
      to Cd intoxication, which may mean that the replenishment of erythrocyte GSH
      content is via GSH-R. The glutathione-S-transferase (GST) activity increased
      significantly with Cd intoxication; however, treatment with antioxidants prior to
      Cd treatment decreased erythrocyte GST activity. The results show that Cd-induced
      LPO decreased the antioxidant capability of the erythrocytes, causing erythrocyte
      membrane damage.

PMID- 9176865
TI  - Influence on the selenium concentration and selenium intake of infants of infants
      of ingredients in Spanish homogenised infant beikosts.
AB  - Selenium (Se) concentration in 13 homogenised beikosts ("any additional food used
      in infant nutrition different from human milk and formulas") was investigated, as
      well as the influence of ingredients on Se concentration in three beikost types
      (meat, vegetables and fish). Levels of Se varied widely, ranging from 20
      micrograms/kg d.w. for mixed vegetables to 258 micrograms/kg d.w. for hake with
      rice. These values increased as high-protein ingredients (meat or fish) were
      included. Fish-based beikosts showed the highest contribution of Se, covering
      more than 50% of the RDA in the USA for infants from 6 to 12 months old. The best
      Se sources were meat and fish, and their contributions to Se concentrations in
      the final products were 85.3% for chicken with rice and 75% for hake and
      vegetables.

PMID- 9176866
TI  - Testis damage induced by zinc deficiency in rats.
AB  - Male Wistar rats were fed a Zn-deficient diet (1.2 mg/kg of Zn) for 28 days.
      Testes were then studied by light and electron microscopy. Zn deficiency induced
      necroses of precursors of germ cells leading to tubular atrophy and affected
      differentiation of spermatids. This was expressed by the occurrence of 2-4
      axoneme-dense fibre-mitochondria complexes in one spermatid. Moreover, outer
      dense fibres, which normally contain 90% of sperm Zn, were "uncoiled" and
      flattened. The multiplication of the axoneme-dense fibre-mitochondria complexes
      induced by Zn deficiency might have been produced by an increase of Fe in
      spermatids and an increased formation of oxygen free radicals.

PMID- 9176867
TI  - Relationships between iron and zinc metabolism: predictive value of digestive
      absorption on tissue storage.
AB  - The responses of animals to intake of a trace element could vary if it is
      ingested with a single test meal or due to chronic intake. The metabolic
      relationships between zinc (Zn) and iron (Fe) were assessed in the young animal
      by comparing their digestive absorption studied at the beginning of the study
      with their tissue storage after two months of being fed on experimental diet.
      Diets supplied adequate intakes of Fe (45 and 300mg/kg diet) and Zn (14 and 45
      mg/kg). A significant effect of Fe supply (p < 0.0001) but not of Zn was
      displayed on Fe absorption; both Fe and Zn diet concentrations influenced Zn
      absorption (p < 0.01, p < 0.0001). Fe and Zn organ contents significantly
      correlated with the amount absorbed during the metabolic balance (p < 0.0001).
      There was a positive correlation between liver, bone, and muscle Fe and Fe
      absorption (mg/d)(p < 0.0001), and Fe absorption and bone and muscle Zn (p <
      0.04) and a negative one with liver Zn (p < 0.0001); a positive correlation was
      displayed between Zn absorption (mg/d) and Zn organ content (p < 0.0001). There
      was no correlation between Zn absorption and Fe tissue content (p > 0.05). This
      study suggests that interactions occur at every step of Fe and Zn metabolism; Fe
      is more efficient in altering Zn storage than the reverse. The organism seems to
      be unable to diminish the consequences of an unbalanced diet and digestive
      absorption. Care must be taken to give the young growing balanced diets.

PMID- 9176868
TI  - Udder orf infection and its role in ovine clinical mastitis caused by Pasteurella
      haemolytica.
AB  - During an experimental study of ovine subclinical mastitis caused by coagulase
      negative staphylococci, an outbreak of contagious ecthyma occurred among ewes
      unvaccinated against parapox virus. The same group of ewes developed a high rate
      (43.7%) of clinical mastitis caused by Pasteurella haemolytica. The rate of
      clinical mastitis among ewes vaccinated against parapox virus was very low (3.7%)
      suggesting that the presence of orf in the unvaccinated ewes was contributing to
      the high rate of clinical mastitis. An examination of the iron, sodium, potassium
      and albumin concentration of milk collected from 16 unvaccinated and nine
      randomly selected vaccinated ewes before experimental infection with coagulase
      negative staphylococci or their uninfected control mammary glands indicated
      significant differences in the iron (p < 0.0001) and sodium (p = 0.01)
      concentration. Increased iron concentration in the milk may have assisted in the
      development of udder infection caused by P. haemolytica as iron is easily
      utilised by this bacterium.

PMID- 9176869
TI  - Fluctuation of zinc, copper, magnesium and calcium concentrations in guinea pig
      tissues after administration of captopril (SQ 14225).
AB  - The effect of the administration of captopril on Zn (zinc), Cu (copper), Ca
      (calcium) and Mg (magnesium) concentrations in guinea pig tissues was studied.
      For nine weeks 2 mg captopril per kg b.w. were administered daily to adult male
      guinea pigs intraperitoneally. The concentrations of the studied metals were
      determined in several tissues. Captopril significantly decreased Zn concentration
      in liver, Cu concentration in liver, adrenals, jejunum, urine and hair and Mg
      concentrations in blood and urine. A significant increase was observed in
      testicular and epididymal Zn, in heart, epididymal and fecal Cu, in Mg
      concentration of lung, kidney, adrenals, jejunum, epididymis and hair and in Ca
      concentrations in brain, heart, lung, kidney, spleen and stomach. No significant
      changes were observed in the colon and the thigh bone concentrations of the
      various elements tested. In conclusion Captopril treatment can produce
      translocation and/or elimination of Zn, Cu, Mg and Ca ions in various tissues of
      guinea pigs.

PMID- 9176870
TI  - Effects of endurance training on skeletal muscle oxidative capacities with and
      without selenium supplementation.
AB  - The purpose of this study was to examine the changes induced by endurance
      training, with or without selenium (Se) supplementation on: 1) mitochondrial
      activity of succinate dehydrogenase (SDH) and cytochrome c oxidase (Cyt Ox),2)
      the myosin heavy chain (MHC) expression in muscle fibers and 3) their association
      with aerobic performance. Twenty-four male students volunteered to participate in
      this double blind study: selenium (Sel, N = 12) vs placebo (Pla, N = 12). During
      a 10-wk endurance training program, the Sel group received a daily Se
      supplementation containing 180 micrograms of organic selenium (selenomethionine),
      while the Pla group received a placebo. Before (Pre) and after (Post) the program
      (3 sessions wk-1) an endurance exercise (Capmax) was performed in order to
      determine the aerobic endurance capacity assessed by the total oxygen uptake
      during the running test (VO2tot). All parameters of aerobic performance were
      increased in both groups, concomitantly to a rise in mitochondrial Cyt Ox
      activity. Two positive relationships were found: 1) between type I MHC and VO2tot
      increments (r = 0.65, P < 0.05), 2) between training volumes and VO2tot
      increments (r = 0.53, P < 0.05; N = 23). The training program produced an 8.2%
      significant increase in type I MHC (P < 0.05) while type II MHC decrease was not
      significant (-4.4%). Although they were almost non-existent before the program,
      muscle fibers which co-expressed type I and II MHC displayed a marked increase
      afterwards (4.9 +/- 5.7 vs 1.1 +/- 2.1%, P < 0.05). Muscle GSH-Px activity, at
      rest, did not respond to endurance training or Se supplementation. The results
      suggest that the neuromuscular system is still in an evolutive state after 10
      weeks of endurance training, and that selenium supplementation has no effect on
      endurance training-induced adaptations.

PMID- 9176871
TI  - Erythrocyte magnesium in elderly patients: not a reliable guide to magnesium
      status.
AB  - To assess body magnesium status in various illness states in older people by
      measurement of serum magnesium (S Mg) and erythrocyte magnesium (E Mg) and to
      explore the limitations of E Mg measurement. S Mg and E Mg were measured in 150
      consecutive out-patients, mean age 77 years, and in 100 consecutive in-patient
      admissions, mean age 80 years. Results were analysed for different diagnostic
      groups S Mg was normally distributed for both in-patients and out-patients, mean
      values 0.79 mmol/l and 0.77 mmol/l respectively. In-patient E Mg concentrations
      were often higher but the distribution was considerably skewed, median 2.28
      mmol/l, mean 2.35 mmol/l. Out-patient E Mg concentration followed a near normal
      distribution, median 2.32 mmol/l, mean 2.30 mmol/l. There was a significant
      correlation between E Mg and S Mg for out-patients, R = 0.29 (p < 0.001). In
      patients with infections and pressure sores had significantly raised E Mg
      concentrations but normal or low S Mg. High E Mg concentrations in illness are
      likely to be due to alterations in characteristics of the erythrocytes themselves
      rather than an indication of body magnesium excess. E Mg concentrations in
      illness should be interpreted with caution.

PMID- 9176872
TI  - Serum copper, zinc and magnesium levels in children with enterobiosis.
AB  - Levels of serum copper (Cu), zinc (Zn) and magnesium (Mg) were determined in the
      sera of 250 children aged between 6 and 13. Of these children, 180 were infected
      only with Enterobius vermicularis. The remaining 70 children were without
      parasitic or bacterial infection and made up the control group. The cellophane
      tape method was used to detect E.vermicularis infection. The levels of Cu, Zn and
      Mg in the serum samples were measured with the Perkin- Elmer 2380 Atomic
      Absorption Spectrophotometer. Evaluation by the student-t test showed that the
      means of the Cu, Zn and Mg in the serum were significantly lower in the infected
      group than in the control group. Thus, in this study, we found that E.
      vermicularis adversely affects the level of elements such as Cu, Zn, and Mg in
      serum.

PMID- 9176874
TI  - Review of publications.

PMID- 9176873
TI  - Biological levels of aluminium after use of aluminium-containing bone cement in
      post-otoneurosurgery.
AB  - Use aluminium-containing biomaterials in otoneurosurgery for reconstitution of
      bone in contact with cerebrospinal fluid (CSF) also led to cases of
      encephalopathy and death. We report aluminium (Al) concentrations in the
      biological fluids of six French patients following use of Al-containing bone
      cement in otoneurosurgery. In five patients, the mean plasma Al levels
      (microgram/L) were: 1.20 +/- 0.05 (case 2), 9.20 +/- 0.10 (case 3), 1.00 +/- 0.05
      (case 4), 2.80 +/- 0.05 (case 5) and 2.00 +/- 0.05 (case 6). In case 1, Al
      concentrations were 176 micrograms/L in the postauricular CSF accumulation, 34
      micrograms/L in the pontocerebellar angle and 4 and 6 micrograms/L in the lumbar
      shunt. As a precautionary measure, in the first three cases the biomaterial was
      removed soon after the intervention, and no increase in plasma or CSF Al was
      observed. In the other cases, absence of neurobiological symptoms and normal
      concentrations of Al in plasma led neurosurgeons not to extract this biomaterial.
      Al assay thus may be considered to be a complementary and at times a decision
      generating factor. Care is needed at all stages from sampling through analysis
      because Al is ubiquitous and factually high results may be clinically misleading.
      Herein, such considerations are discussed in conjunction with the neurotoxicity
      of this metal in man. In addition, the authors call for in-depth preliminary
      trials of these biomaterials in animals prior to introduction on the market.

PMID- 9176875
TI  - Diagnostic procedure on suspicion of zinc deficiency. Society for Minerals and
      Trace Elements.

PMID- 9176876
TI  - Images of molecular medicine.

PMID- 9176877
TI  - Stem cells to treat HIV.

PMID- 9176878
TI  - Telomerase as a marker for cancer.

PMID- 9176879
TI  - Faster, cheaper sequencing using anchored PCR.

PMID- 9176880
TI  - Molecular aspects of headaches and migraines. 7th International Headache Research
      Seminar. Copenhagen, Denmark, 22-24 November 1996.

PMID- 9176881
TI  - Progress in psoriasis. Psoriasis: from gene to clinic. London, UK, 5-7 December
      1996.
AB  - In a meeting dedicated to a single common complex disease such as psoriasis, it
      is not surprising that many unanswered questions were raised. However, the
      meeting highlighted the impressive progress being made in psoriasis research at
      both the investigative and the therapeutic levels. A follow-up meeting is to take
      place in 1999, when further characterization of susceptibility gene loci should
      be available, together with data concerning the selective nature of disease
      causing T cells and the antigens that trigger the disease. Identification of
      these critical factors should allow development of highly specific therapeutic
      agents, some of which are beginning to find their way into clinical development.

PMID- 9176882
TI  - Coronary heart disease and genetics in epidemiologist's view.
AB  - We are just beginning to uncover the genetic determinants of coronary heart
      disease. The genotype-phenotype associations are complex as a consequence of
      pleiotropy, variation with age, selection owing to the high lethality of the
      disease, and interactions between genes and with environmental factors.
      Nevertheless, identification of the gene variants involved in the chronic and
      acute processes of coronary heart disease appears possible; this could
      considerably improve our understanding of the aetiology and mechanisms of this
      disease. Simultaneous analysis of several predisposing alleles should provide the
      means to identify high-risk individuals and to adapt therapeutic approaches to
      the genetic make-up of patients.

PMID- 9176883
TI  - Molecular genetic events in the development and progression of ovarian cancer in
      humans.
AB  - Ovarian tumor development is characterized by specific clinical and pathological
      features that provide an interesting model of carcinogenesis: first, the pre
      invasive and even invasive lesions are difficult to detect; second, a group of
      cases with a known familial predilection constitute an important heredltary model
      of carcinogenesis; and third, the category of morphologically borderline ovarian
      tumors (tumors of low malignant potential) poses several unanswered questions
      such as: what histologic criteria should be used for their diagnosis; what is
      their natural history; and what is their molecular relationship to invasive
      tumors? Recently, molecular studies have contributed to a better understanding of
      the biology of these tumors, their behavior in vivo, and their response to
      therapy. This article summarizes the most recent molecular advances.

PMID- 9176884
TI  - Selectins, T-cell rolling and inflammation.
AB  - The selectins, a family of Ca(2+)-dependent lectins, are expressed on inflamed
      vascular endothelium and some leukocyte subsets, and mediate adhesive contacts
      between blood cells and vessel walls. These interactions are loose and
      reversible, operate under conditions of shear flow, and result in leukocyte
      rolling along the vessel wall. The structure of the selectins and their ligands
      makes them uniquely suited for supporting the type of bond formation and
      dissociation that must prevail in order for a cell to be able to roll under
      conditions of flow. Because rolling precedes (and appears to be essential for)
      the integrin-mediated firm arrest before extravasation in response to
      inflammatory or infectious stimuli, inhibition of selectin function has potential
      for anti-inflammatory therapy, but also presents some significant challenges
      because of the complexity of the processes involved.

PMID- 9176885
TI  - Oncogenic mechanisms mediated by DNA methylation.
AB  - Cancer is often viewed as a genetic process in which the developing cancer cell
      acquires successive mutational lesions that each provide the cell with a growth
      or survival advantage. The focus on genetic alterations in cancer research has
      perhaps led to an underestimation of the contribution by epigenetics. Epigenetic
      events are heritable alterations in gene function that are mediated by factors
      other than changes in primary DNA sequence; 5-methylcytosine DNA methylation is a
      good example. This article reviews current insights into the contribution of DNA
      methylation to mutational and epigenetic mechanisms of oncogenesis.

PMID- 9176886
TI  - Phosphorus metabolites in different muscles of the rat leg by 31P image-selected
      in vivo spectroscopy.
AB  - The difference in concentration of phosphorylated metabolites in muscles with
      different fiber composition was studied in vivo by localized 31P nuclear magnetic
      resonance spectroscopy in the rat hindlimb 120-160 microliters volumes were
      selected in regions containing the soleus and gastrocnemius muscles.
      Concentrations of phosphocreatine (PCr), adenosine triphosphate and inorganic
      phosphate (Pi) were determined and intracellular pH was calculated in the
      respective muscle groups. The highest level of PCr was found in the gastrocnemius
      muscle, containing 30.7 mmoles/dm3 tissue compared to 22.3 mmoles/dm3 in the
      soleus muscle. Pi was significantly lower in gastrocnemius (1.9 mmoles/dm3) than
      in soleus (3.2 mmoles/dm3). The ATP concentration was 6.7 and 6.4 mmoles/dm3 and
      pH was determined to 7.11 and 7.09 in the gastrocnemius and soleus muscle,
      respectively. Our NMR data show that it is possible to measure high-energy
      phosphates with precision in small localized volumes with the ISIS method using a
      Helmholtz coil. Earlier biochemical data are confirmed by these in vivo NMR
      results. Localized in vivo 31P NMR spectroscopy can contribute to the
      understanding of the underlying mechanisms of several metabolic events in
      different regions of the tissue. The method can be used for future studies of
      varying ischemia tolerance, varying degrees of adaptation to exercise with regard
      to oxidative capacity, and pH compartmentation in muscles with different fiber
      composition.

PMID- 9176887
TI  - Interpretation of BOLD MRI signals in rat brain using simultaneously measured
      near-infrared spectrophotometric information.
AB  - The purpose of this paper is to investigate the origin of the signal changes in
      the blood oxygenation level dependent effect (BOLD) and the influence of oxygen
      metabolism by utilizing near-infrared spectrophotometry (NIRS), which can measure
      deoxyhemoglobin (deoxyHb) content in blood vessels and redox states of cytochrome
      oxidase in whole tissue. Simultaneous MRI and NIRS measurements of the rat head
      were performed by changing oxygen concentrations in the inhalant gas. The signal
      intensity based on the BOLD effect depended on the influence of both arterial and
      venous blood deoxygenation in the brain, whose relative contributions differed at
      various points. In this paper, it is noteworthy that the differential apparent
      transverse relaxation rate between two conditions in the brain areas was linearly
      correlated with deoxyHb content determined by NIRS, except in severe hypoxia, and
      that no reduction of cytochrome oxidase occurred under the same conditions. These
      results indicate that the influence of hemodynamic changes on the signal
      intensity of the BOLD effect, and therefore functional MRI, can be elucidated by
      the NIRS information to determine actual changes of blood deoxygenation and blood
      volume.

PMID- 9176888
TI  - Statistics for investigation of multimodal MR imaging data and an application to
      multiple sclerosis patients.
AB  - Magnetic resonance spectroscopy can image axonal damage specifically based on
      changes in N-acetyl aspartate (NAA), a neuronal marker. We have developed
      statistical methods for multimodal analysis of MR spectroscopic images. These
      methods, which are extensions of mixed-effect models, have allowed us to quantify
      differences in images from different subgroups of patients with multiple
      sclerosis (MS) and to determine the dependence of chemical pathology on clinical
      disability, duration of disease and lesions on T2-weighted MRI. Statistical power
      was improved by using all reliable resonance intensities in the spectroscopic
      images while taking into consideration the intra-subject correlations. We studied
      17 normal subjects, 14 patients with relapsing remitting (RR) MS and 21 patients
      with chronic progressive (CP) MS. The ratio of resonance intensities of N
      acetylaspartate over creatine (Cr) was found to be significantly lower than
      normal in normal appearing white matter (NAWM) of both RR and CP patients (19.6%
      in RR, 28.8% in CP), NAA/Cr was decreased even more in MS plaques than in NAWM
      (44.2% in RR, 17.7% in CP), NAA/Cr was correlated with clinical disability (p <
      0.02) and disease duration (p < 0.1). Our results suggest that, in this setting,
      MRS reflects accumulated neuronal loss or damage and can be used as a measure of
      disease severity. The methods developed provide opportunities to evaluate the
      relationship between inflammation, demyelination, axonal loss and clinical
      disability in future studies.

PMID- 9176890
TI  - Metabolic changes associated with vacuolation in murine models of scrapie using
      in vitro 1H-NMR spectroscopy.
AB  - In this study, metabolic changes in the 79A/C3H, ME7/VM, ME7/C3H, 87V/VM and
      22A/SV scrapie mouse models were investigated during the clinical phase of the
      disease, using in vitro proton nuclear magnetic resonance spectroscopy. N-acetyl
      aspartate was found to be significantly reduced in infected mice of the ME7/ C3H
      (40% reduction), ME7/VM (26%) and 79A/C3H (17%) models when compared to control
      mice, but not in the 87V/VM and 22A/SV models. The concentration of choline
      containing compounds and creatine remain unchanged in all models when compared
      with control murine brains. The level of N-acetyl-aspartate reduction correlated
      with the extent of grey-matter brain vacuolation. The levels of myo-inositol were
      found to be significantly increased in the ME7/VM (143%) and 79A/C3H (132%)
      models only and no significant changes were observed in the ME7/C3H, 87V/VM and
      22A/SV models. These changes did not correspond to the severity of gliosis.

PMID- 9176889
TI  - In vivo 31P NMR spectroscopy of human musculoskeletal tumors as a measure of
      response to chemotherapy.
AB  - The value of in vivo 31P NMR spectroscopy to provide indicators of response to
      cytostatic chemotherapy was studied in patients with malignant musculoskeletal
      tumors. Characteristics of untreated cancers were strong signals of PME and PDE,
      moderately increased Pi and low PCr. The intracellular pH was slightly alkaline.
      The intracellular concentration of free magnesium was 70% of that in muscle.
      Spectroscopic findings at different times of therapy were compared with the
      percentage of tumor necrosis after surgical resection in 28 patients. In follow
      up studies, energy-rich phosphates declined in nonresponders, while PME, Pi and
      frequently PDE increased. Treatment response appeared to involve the reversal of
      these trends. In five responders, a biphasic pattern was observed, i.e. initially
      the spectrum changed into that of severely ischemic cell injury followed by a
      successive phase of apparent 'tumor activation'. Pretreatment levels of
      (PCr+Pi)/total phosphate > or = 0.35 and PCr/ alpha-NTP > or = 1.5, an
      accelerated increase in total low-energy phosphates/total high-energy phosphates
      (> or = 3.0%/day) after the initial drug application, and a long-term decrease (<
      or = -0.4%/day) during later therapy were highly indicative of tumor response to
      chemotherapy. Such spectroscopic predictors for treatment response proved to be
      superior to currently used indices such as tumor size.

PMID- 9176891
TI  - In vivo 31P MRS evaluation of ganciclovir toxicity in C6 gliomas stably
      expressing the herpes simplex thymidine kinase gene.
AB  - Phosphorus MRS was evaluated as a monitor of tumour therapeutic response to the
      herpes simplex virus thymidine kinase suicide gene therapy paradigm. In vivo 31P
      spectra were obtained from subcutaneous rat C6 gliomas constitutively expressing
      the HSVtk gene post treatment with ganciclovir (GCV, 15 mg/kg i.p., twice-daily).
      Significant regression (p < 0.1) of tumour volume was observed 10 days after
      beginning GCV administration. However, no changes in tumour pH or energy
      metabolites from pre-treatment values were observed. High-resolution 31P spectra
      of tumour extracts revealed a statistically significant reduction in the
      phosphocholine to phosphoethanolamine ratio six days post-GCV administration.
      These results indicate that the HSVtk/GCV-induced killing of tumours is not
      associated with corresponding changes in 31P MRS-observable energy metabolites
      and pH. The observed reduction in the PE/PC ratio may provide a non-invasive in
      vivo indicator of therapeutic efficacy.

PMID- 9176892
TI  - Current awareness in NMR in biomedicine.

PMID- 9176893
TI  - Cellular pharmacology and molecular biology of the trabecular meshwork inducible
      glucocorticoid response gene product.
AB  - Studies of the effects of glucocorticoid (GC) and oxidative stress stimuli in
      differentiated cultures of human trabecular meshwork (HTM) cells have provided
      the rationale for our studies of a major new gene termed TIGR (trabecular
      meshwork inducible GC response). The TIGR clone was isolated by differential
      library screening using selection criteria based on the induction pattern of a
      new protein/glycoprotein found in HTM cultures after prolonged but not brief
      exposure to GCs. This GC induction pattern matched the time course and dose
      response required for intraocular pressure elevation in patients receiving
      corticosteroids. The very large, progressive induction of TIGR combined with
      specific structural features of its cDNA suggested that TIGR should be considered
      a candidate gene for outflow obstruction in glaucoma. Among the properties of
      TIGR cDNA were a signal sequence for secretion, several structural features for
      interactions with glycosaminoglycans and other glycoproteins and putative sites
      for cell surface interactions. In addition, the leucine zippers in the structure
      were related to TIGR-TIGR oligomerization that was shown to occur with native and
      recombinant TIGR protein. The verification that TIGR was a major stress response
      protein in HTM cells following hydrogen peroxide (or phorbol esters) exposure
      provided a potential link between GC and oxidative mechanisms thought to be
      involved in glaucoma pathogenesis. Pharmacological evaluation showed that basic
      fibroblast growth factory and transforming growth factor beta decreased the GC
      induction of TIGR, and certain nonsteroidal anti-inflammatory drugs protected
      against both GC- and oxidation-induced stress responses in HTM cells. Our recent
      studies of TIGR's genomic structure have shown motifs in the promoter region that
      suggest a basis by which multiple hormonal/environmental stimuli can regulate
      TIGR production and by which putative genetic alterations could lead to an
      overexpression of the protein. Further application of cell biology/biochemistry,
      molecular biology, genetic and histological approaches will be helpful in
      understanding the role of TIGR in different glaucoma syndromes.

PMID- 9176894
TI  - Ultrastructural changes in the trabecular meshwork of juvenile glaucoma.
AB  - Trabeculectomy specimens from 11 patients with juvenile glaucoma were studied by
      electron microscopy and quantitatively evaluated. In all cases, large amounts of
      extracellular material arranged in a fingerprint-like pattern, resembling
      basement-membrane-like material (FBM) was found, similar to that described in
      steroid-induced glaucoma. This material was found mainly within the inner
      cribriform and outer corneoscleral regions of the trabecular meshwork, and caused
      the cribriform layer to be greatly thickened. FBM was also intimately associated
      with trabecular cells, which frequently appeared activated. In 3 cases, there was
      also an increase in fine fibrillar material which resembled that found in eyes
      with steroid-induced glaucoma. The amount of sheath-derived plaque material,
      which is increased in primary open angle glaucoma, was greatly increased in the
      subendothelial layer adjacent to Schlemm's canal.

PMID- 9176895
TI  - Trabecular meshwork phagocytosis in glaucomatous eyes.
AB  - Trabecular meshwork cells are actively phagocytic and may function to keep the
      drainage pathways free of cellular debris, pigment and other material. A decrease
      in phagocytic capacity has been proposed in the pathogenesis of glaucoma. This
      study was performed to compare the phagocytic capability of the human trabecular
      meshwork in glaucomatous and normal human eyes. The anterior segments of 6 donors
      with glaucoma (primary open-angle glaucoma, POAG: 5 donors; pseudoexfoliative
      glaucoma, PEX: 1 donor) and 6 normal donors were placed in perfusion organ
      culture. During the final 24 h of culture, latex microspheres, labeled with FITC
      and coated with antibodies, were perfused into the anterior segments. Eyes were
      then fixed, the trabecular meshworks were treated with a rhodamine-labeled
      secondary antibody, sectioned and the number of ingested beads determined with
      the laser scanning confocal microscope. Nuclei were quantitated and used to
      calculate the phagocytic index of each eye (number of ingested beads/number of
      nuclei). Anterior segments of glaucomatous donors were cultured for 1-3 days, as
      a preliminary culture study had revealed that culture of glaucomatous anterior
      segments is successful in only 50% when cultured for 21 days. Specimens of normal
      donors were cultured for 21 days. Ingested beads appeared green and could be
      differentiated from noningested beads, which appeared red, using appropriate
      wavelengths of the laser. Bead ingestion was confirmed with electron microscopy
      and the use of a secondary antibody labeled with horseradish peroxidase.
      Ingestion rates appeared similar among all three groups of eyes: POAG, 3.8
      beads/cell; PEX, 3.3 beads/cell; normal, 3.5 beads/ cell. No evidence of
      significant migration or loss of trabecular cells was noted. Cell counts were not
      significantly different: POAG, 127 +/- 40 cells/section; normals, 136 +/- 49
      cells/section. In conclusion, the phagocytic ability of the trabecular meshwork
      appears similar between eyes with POAG and normal eyes in perfusion organ
      culture. Cell loss after phagocytosis was not observed in these single-exposure
      experiments.

PMID- 9176896
TI  - Effect of diuretics, channel modulators and signal interceptors on contractility
      of the trabecular meshwork.
AB  - Measurements of isometric tension were performed on isolated trabecular meshwork
      (TM) and ciliary muscle (CM) strips of the bovine eye. Anterior segments of
      bovine eyes with well-preserved TM were perfused to measure outflow rate. (1)
      Bumetanide (10(-4) mol/l) and hydrochlorothiazide (10(-4) mol/l) did not change
      the contractility of TM and CM strips in the presence or absence of carbachol.
      Ethacrynic acid dose-dependently relaxed TM and CM strips precontracted either by
      carbachol or endothelin. (2) Cytochalasin D totally relaxed TM and CM strips
      precontracted by carbachol. The outflow rate almost doubled after application of
      cytochalasin D. (3) The effects of various modulators of K+ and Ca2+ channels are
      summarized. Carbachol and endothelin are postulated to modify nonselective cation
      channels. An effective blocker of nonselective cation channels (flufenamic acid)
      relaxed TM and CM precontracted by carbachol or endothelin. These relaxing
      effects were independent of the relaxing effects of ethacrynic acid and
      isosorbide dinitrate. (4) Evidence for the presence of various transporters and
      receptors in TM cells is summarized. (5) The TM per se is a contractile element
      which is involved in the regulation of aqueous humor outflow. The contractility
      of TM and CM cells is differently modulated.

PMID- 9176897
TI  - Choroidal ganglion cell plexus and retinal vasculature in monkeys with laser
      induced glaucoma.
AB  - The choroid of primates possesses an elaborate nitrergic nerve fiber plexus
      containing a great number of ganglion cells. Postganglionic nerve fibers
      innervate mainly the choroidal vasculature. In addition, the choroid contains an
      elastic muscular system closely associated to the vasculature. The goal of the
      present investigation was to analyze how sustained IOP elevation would affect the
      choroidal vasculature with its specialized innervation and the adjacent retina.
      For this purpose the posterior eye segment of 15 rhesus monkeys which after laser
      coagulation of the trabecular meshwork developed elevated IOP up to 4 years were
      studied using immunohistochemical and histochemical methods, and scanning
      electron microscopy of corrosion casts. The most striking finding was a
      significant reduction of choroidal thickness and loss of choroidal ganglion cells
      and nerve fibers, especially in the central portion of the choroid. Corrosion
      casts of the choroidal vasculature showed a slight decrease in capillary density
      and a decrease in length of the arterioles in glaucomatous eyes. Whole mount
      preparations of the retina stained for NADPH diaphorase revealed a significant
      reduction in positively stained amacrine cells, reduction in diameter of
      arterioles and changes in the staining pattern of the retinal vasculature,
      particularly in the perimacular region.

PMID- 9176898
TI  - Retinal capillary hemodynamics and VEP/pressure tolerance: evidence of retinal
      microcirculatory compromise in treated glaucomatous eyes.
AB  - Measurements of retinal leukocyte velocity were made in single eyes of 6
      glaucomatous adults and 9 normal subjects at each of 4 discrete levels of IOP
      elevation assigned according to the characteristics of prior pattern-evoked
      cortical potential pressure tolerance measurements. Glaucomatous eyes failed to
      demonstrate any stabilization in retinal leukocyte velocity at pressures above 45
      mm Hg, with velocities 33% lower than normal for a comparable degree of IOP
      elevation (p < 0.012). Even at baseline IOP, leukocyte velocity was 27.2% slower
      in the treated glaucomatous eyes than in normal control eyes (p < or = 0.013),
      despite comparable baseline IOP levels in both groups.

PMID- 9176899
TI  - Ocular blood flow in experimental glaucoma: a study in cynomolgus monkeys.
AB  - Experimental glaucoma was induced in 1 eye of 6 cynomolgus monkeys by laser
      treatment of the trabecular meshwork. In 5 of the 6 monkeys the increased
      intraocular pressure (IOP) caused marked glaucomatous damage in the experimental
      eye. Ocular blood flow was determined with labeled microspheres 4 years after the
      laser treatment. IOP was regulated with an external reservoir. With the same
      perfusion pressure in both eyes no statistically significant difference was
      observed between the 2 eyes for total ocular blood flow or for blood flow through
      any of the ocular tissues. Total ocular blood flow was 343.5 +/- 61.4 mg/min
      (mean +/- SEM) in the control eye and 385.3 +/- 107.7 mg/min in the experimental
      eye.

PMID- 9176900
TI  - The three-dimensional structure of the connective tissue in the lamina cribrosa
      of the human optic nerve head.
AB  - Comprehensive understanding of the three-dimensional structure of the
      extracellular matrix (ECM) of the lamina cribrosa is central to understanding its
      role in health and disease, particularly how changes in configuration might
      precipitate nerve fibre death in glaucoma. Research until recently has relied
      almost entirely on light and scanning electron microscopy (SEM) to investigate
      the ECM of the lamina cribrosa. In this paper, we review the contribution of
      these methods to current understanding of the three-dimensional structure of the
      lamina ECM, highlight their potential weaknesses and emphasise that there is
      still much to be revealed about the structure of the lamina ECM. We then describe
      our development of confocal microscopy and computer reconstruction as a new and
      alternative method of investigating the three-dimensional structure of the lamina
      ECM. We show how optical sectioning allows the confocal microscope to acquire
      three-dimensional images of the lamina ECM without the degree of tissue
      disruption associated with preparation for SEM and demonstrate the versatility of
      analysis of these images by computer reconstructive software. A case is made for
      confocal microscopy and computer reconstruction contributing to our understanding
      of this important but complex and delicate structure.

PMID- 9176901
TI  - Peroxide-induced damage in lenses of transgenic mice with deficient and elevated
      levels of glutathione peroxidase.
AB  - Transgenic mice with elevated glutathione peroxidase (GSHPx) activity and gene
      knockout animals with a deficiency of the enzyme were used to investigate the
      role of GSHPx in defending the lens against H2O2-induced damage. The effects of
      peroxide on cultured lenses were determined by using light and transmission
      electron microscopy to evaluate morphological changes occurring in the epithelium
      and superficial cortex of the central and equatorial regions of the lens. DNA
      single-strand breaks in the epithelium were also examined. Following a 30-min
      exposure to 25 microM H2O2, lenses from normal animals showed distinct changes in
      the morphology of both the epithelium and superficial cortex. The damage to these
      cells was extensive in lenses of gene knockout mice in which activity of GSHPx
      was undetectable. In marked contrast, lenses of transgenic mice, which had 5-fold
      higher activities of GSHPx, were able to resist the cytotoxic effects. Similar to
      damage to cell morphology, the extent of DNA strand breaks was significantly
      lower (40% of control) in H2O2-exposed lenses as compared to normal lenses while
      DNA damage in gene knockout lenses was 5 times greater than that of GSHPx-rich
      transgenic lenses. The present studies extend our previous findings on the role
      of the glutathione redox cycle in the detoxification of peroxide and demonstrate
      that an increase in GSHPx activity protects the lens against peroxide-induced
      changes in cell morphology and DNA strand breaks.

PMID- 9176902
TI  - Nitrergic nerve cells in the primate ciliary muscle are only present in species
      with a fovea centralis.
AB  - Nerve cells positive for NADPH diaphorase (D)/nitric oxide synthase in the human
      ciliary muscle appear to be involved in relaxation of the muscle during
      disaccommodation. To study whether similar cells might mediate disaccommodation
      of the primate ciliary muscle in general, serial sections of the ciliary muscle
      of 5 cynomolgus monkeys (Macaca fascicularis) and 2 owl monkeys (Aotes
      trivirgatus) were stained for NADPH-D. Both monkey species have a ciliary muscle
      system and an accommodative amplitude comparable to that in humans. Positively
      stained cells were frequently observed in the ciliary muscle of all cynomolgus
      monkeys, a diurnal species with a fovea, but never in owl monkeys, a nocturnal
      species without a fovea. The results indicate that NADPH-D-positive and probably
      nitrergic ganglion cells in the ciliary muscle are not present in all primate
      species, but only in those with high requirements for visual acuity. They might
      smoothen the ciliary-ganglion-mediated contraction of the ciliary muscle or
      contribute to the small fluctuations or oscillations of accommodation that are
      observed under steady viewing conditions.

PMID- 9176903
TI  - From the lesson of Harvey Cushing to current knowledge: psychosocial aspects of
      endocrine disease.

PMID- 9176904
TI  - The notion of somatization: an artefact of the conceptualization of body and
      mind.
AB  - BACKGROUND: Somatization is a contemporary notion which derives from the
      conceptualization of body and mind and the resultant concept of disease. The
      common element in this thinking is that the presumed separation of the concepts
      body and mind can be spanned by clinical symptoms. METHODS: This paper examines
      the history of these concepts and the assumptions underlying them. RESULTS: It is
      shown that the debate on the pathological regions of the body-mind relation is of
      early origin. It is reflected in the evolution of concepts of disease and disease
      entities. The ongoing attempts to form a conceptual synthesis have resulted in a
      multiplicity of disease entities and in the notion of somatization. However,
      somatization is shown here to differ conceptually from controversial contemporary
      disease entities with which it often seems intertwined, such as myalgic
      encephalomyelitis and the hypersensitivity syndrome. CONCLUSION: This insight may
      help diminish the ambiguity in this area of research and practice.

PMID- 9176905
TI  - Tactual sensitivity in hypochondriasis.
AB  - BACKGROUND: In his article on amplification, somatization and somatoform
      disorders Barsky [Psychosomatics 1992; 33:28-34] pointed out the importance of
      studying the perception and processing of somatic and visceral symptoms.
      Subsequently, it was demonstrated that hypochondriacal patients are not more
      accurately aware of cardiac activity than a group of non-hypochondriacal
      patients. Authors concluded that hypochondriacal somatic complaints do not result
      from an unusually fine discriminative ability to detect normal physiological
      sensations that non-hypochondriacal patients are unable to perceive. The aim of
      the present study was to investigate tactual sensitivity to non-painful stimuli
      in hypochondriacal patients and healthy subjects. METHODS: Twenty-seven
      outpatients with DSM-III-R hypochondriasis and 27 healthy control subjects were
      compared. In all subjects the two-point discrimination threshold was measured, as
      well as subjective sensitivity to harmless bodily sensations as measured by the
      Somatosensory Amplification Scale. RESULTS: It was found that hypochondriacal
      patients reported more distress and discomfort with benign bodily sensations. The
      two-point discrimination threshold of hypochondriacal patients was not
      significantly lower in patients as compared to controls. CONCLUSIONS:
      Hypochondriacal subjects considered themselves more sensitive to benign bodily
      sensations without being better able to discriminate between two tactual bodily
      signals. These findings of the present study correspond quite closely to those
      reported earlier.

PMID- 9176906
TI  - Somatization, dissociation, and tension-reducing behaviors in psychiatric
      outpatients.
AB  - BACKGROUND: Conceptual and methodological difficulties exist in assessing coping
      behaviors. METHODS: This study investigated coping behaviors in 102 psychiatric
      outpatients. We used the Dissociative Experiences Scale, a 17-item posttraumatic
      stress disorder (PTSD) checklist; 2 measures of somatization (the Wahler Physical
      Symptom Inventory and the Physical Symptom Questionnaire), and 21 questions about
      subject involvement in positive and pathologic tension-reducing behaviors.
      RESULTS: Preliminary data suggest that dissociative symptoms, PTSD-like symptoms,
      and somatization are associated with a variety of positive and pathologic tension
      reducing behaviors. CONCLUSIONS: The results suggest that psychiatric outpatients
      have an array of coping behavior: some are health-promoting, others are
      relatively self-destructive.

PMID- 9176907
TI  - Dental anxiety and illness behaviour.
AB  - BACKGROUND: To analyse the relationship between dental anxiety and illness
      behaviour. METHODS: Dental anxiety was assessed in 165 patients from private
      practice using the Dental Anxiety Scale (DAS), aspects of illness behaviour were
      evaluated by the Illness Attitude Scale (IAS), and aspects of general anxiety
      were analysed by the State Trait Anxiety Inventory (STAI). Dental status was
      documented using the DMFS index and Bleeding-on-Probing index (BOP). RESULTS:
      Multiple regression analysis (explained proportion of variance = 32%) showed that
      dental anxiety was significantly correlated with female gender (t = 3.109, p <
      0.002) and IAS health habits (t = -2.210, p < 0.03). In addition, a correlation
      trend was found between dental anxiety and BOP index (t = -1.789, p < 0.08).
      CONCLUSION: Dental anxiety appears to be a gender-specific phenomenon. Results
      indicate a tendency towards abnormal illness behaviour (i.e. denial of dental
      anxiety) in a considerable proportion of subjects and as a consequence display of
      poor health habits (i.e. counterphobic behaviour). The latter may lead to an
      increased tendency to develop gingivitis as indicated by the correlation trend
      between dental anxiety and BOP index.

PMID- 9176908
TI  - Recidivism in major depressive disorder.
AB  - BACKGROUND: While recidivism has been well studied in psychotic disorders, little
      has specifically been done to determine what differences exist between patients
      admitted multiple times compared with once for major depressive disorder (MDD).
      METHOD: The records of patients admitted with MDD to a large military medical
      center were reviewed during the years 1991-1995. Recidivists were 46 consecutive
      patients admitted three or more times during the period. The comparison sample
      was 50 consecutive patients admitted for the first time in 1993 without
      subsequent admission to our hospital. Patient groups were compared for age,
      gender, comorbidity, and the presence of medical conditions contributing to their
      admission. RESULTS: Repeat hospital admissions for MDD were common. Recidivists
      were more likely to be older, suffer recurrent depression, receive a personality
      disorder diagnosis, receive ECT or have a medical condition contributing to their
      admission, than patients admitted once. Alcohol use disorders or other Axis I
      disorders did not predict recidivism. CONCLUSIONS: For some patients the
      morbidity of MDD in the form of frequent admissions is considerable, perhaps as
      severe as for patients with psychotic disorders. Frequent hospitalizations may
      result from recurrent MDD with or without personality disorder.

PMID- 9176909
TI  - Coping style and social support in women suffering from cluster headache or
      migraine.
AB  - BACKGROUND: Many clinical neurologists have considered cluster headache patients
      to differ from migraine patients as to behavioral patterns. There is, however,
      little empirical validation of such a differentiation. METHODS: Coping profiles
      and social networks were studied in patients suffering from two kinds of
      recurrent headache. Twenty-four female patients with cluster headache, aged 23-72
      years, and 24 age-matched migraine patients with and without aura participated in
      the study. All female cluster patients treated at the neurologic clinic of the
      hospital were included, and consecutive outpatients, who had been referred to the
      policlinics for diagnosis and treatment, whose symptoms agreed with the IHS
      criteria for migraine and who had ages matching the cluster headache patients,
      participated in the study. RESULTS: In the semiprojective coping tests the
      cluster headache patients were found to be statistically significant more
      'positive' as to their anticipated activities in the future compared to the
      migraine patients (p < 0.04). No other statistical differences were found between
      the two groups. Compared to randomly selected and age-matched referents in the
      population. cluster headache patients reported significantly poorer social
      support (p < 0.01), while no other difference was found when the migraine
      patients were compared with controls. CONCLUSIONS: The findings indicate that
      there are differences in perception of anticipated activities and social support
      between patients with cluster headache and migraine.

PMID- 9176910
TI  - Physicians' view of their work environment and organisation.
AB  - BACKGROUND: The objective of this study was to assess physicians' perception of
      their work, organisation and professional development. METHODS: All major
      disciplines at a major regional hospital were studied. Participants responded to
      a structured questionnaire concerning broad aspects of physicians' work. The
      response rate was approximately 78%, with 356 respondents. RESULTS: The results
      show that even though physicians are overall very satisfied with their work, they
      list high workload, lack of influence on daily work and work processes as
      dissatisfactory. Skills utilisation and development are some major areas for
      improvement. Physicians that were aware of the overall mission statement for
      their hospital were more satisfied with and informed about departmental goals.
      Perceived organisational efficiency and leadership qualities were important
      determinants of perceived workload and work climate. CONCLUSIONS: Stress among
      physicians is a growing occupational health concern, impacting negatively on
      patient care. In this article important individual and organisational factors
      related to physician stress are identified and suggestions to assess stress and
      intervene are provided.

PMID- 9176911
TI  - Psychological assessment of patients with idiopathic pruritus ani.
AB  - BACKGROUND: The purpose of this study was to compare psychological profiles in 17
      patients suffering from idiopathic pruritus ani with a control group of 28
      patients showing secondary pruritus ani. METHODS: The two groups completed the
      Mini-Mult personality test and results were compared using chi 2 test and
      analysis of variance. RESULTS: The mean hypomania and depression scale scores
      were greater and smaller respectively in the idiopathic pruritus ani group.
      Nevertheless, the percentage of abnormal psychological profiles was not
      significantly different between the two groups. CONCLUSIONS: It seems arbitrary
      to systematically ascribe psychogenic aetiologies to idiopathic pruritus ani even
      though psychological factors may be present in individual patients.

PMID- 9176912
TI  - Biology of airway inflammation: from immunology to altered responsiveness.

PMID- 9176913
TI  - Basic concepts in lung immunology.

PMID- 9176914
TI  - Lymphocyte subsets in experimental bronchopulmonary inflammation and
      hyperresponsiveness.

PMID- 9176915
TI  - Adhesion molecules and the recruitment of eosinophils to the airways.

PMID- 9176916
TI  - Immunobiology of eosinophils in allergy and inflammation.

PMID- 9176917
TI  - Cytokines involved in the downregulation of allergic airway inflammation.

PMID- 9176918
TI  - Interleukins involved in the pathogenesis of chronic airway inflammation.

PMID- 9176919
TI  - Role of the respiratory epithelium in asthma.

PMID- 9176920
TI  - Smooth muscle as a direct or indirect target accounting for bronchopulmonary
      hyperresponsiveness.

PMID- 9176921
TI  - Genetics of airway responsiveness in the inbred mouse.

PMID- 9176922
TI  - Differential relationships between positive and negative symptoms and
      neuropsychological deficits in schizophrenia.
AB  - This study assessed the relationships between positive and negative clinical
      symptoms and specific neuropsychological deficits in a group of stable
      schizophrenic patients. METHOD: Thirty patients were assessed using the Positive
      and Negative Syndrome Scale (PANSS) for schizophrenia and a battery of cognitive
      tests. The PANSS assessments were done by a group of raters blind to the results
      of cognitive tests, while the cognitive tests were conducted by a different group
      of raters who remained blind to the PANSS scores. RESULTS: We found that,
      although positive and negative symptoms showed a trend toward direct correlation
      with each other, they correlated with distinct cognitive deficits. Patients with
      higher negative scores had more perseverative responses, perservative errors, and
      completed fewer categories on the Wisconsin Card Sorting Test; they also
      experienced more difficulties on trail making and verbal fluency tests. On the
      other hand, positive symptoms were associated with poor performance on the Digit
      Span, particularly the Digit Span Forward. CONCLUSIONS: Our findings are in
      agreement with previous reports that negative symptoms may be associated with
      poor performance on cognitive tests reflecting particularly frontal function.
      Positive symptoms, on the other hand, seem to be associated with poor attention,
      specifically of auditory type, and thus, possibly with dysfunction within the
      more widespread neural networks underlying attention. Our findings support the
      hypothesis that positive and negative symptoms may be associated with distinct
      neuropsychological deficits and thus with distinct neurological substrates and
      point to the need to address both positive and negative dimensions when studying
      schizophrenia.

PMID- 9176923
TI  - Cerebral perfusion correlates of negative symptomatology and parkinsonism in a
      sample of treatment-refractory schizophrenics: an exploratory 99mTc-HMPAO SPET
      study.
AB  - There is a well recognized clinical overlap between primary and secondary
      neuroleptic negative symptoms in schizophrenia, but their cerebral substrates are
      probably different. The study of these substrates could contribute to a better
      understanding and management of these syndromes. In the present work, the
      cerebral perfusion correlates, as an indirect measure of the underlying neuronal
      function, of negative symptoms and parkinsonism were studied with single-photon
      emission tomography in a group of treatment-refractory paranoid schizophrenic
      patients. Perfusion ratios with respect to the homolateral cerebellum were
      compared with a normal database. Correlation coefficients were calculated between
      perfusion ratios, negative symptoms and parkinsonism scores on exploratory
      grounds. As a group, the patients showed a bilateral, but predominantly left
      sided, hypofrontality and hypotemporality, as well as an increased perfusion in
      right basal ganglia. Negative symptoms scores negatively correlated with
      prefrontal perfusion, while parkinsonism positively correlated with the activity
      of primary motor and sensory cortex. These findings support the existence of
      different cerebral substrates for primary and secondary negative symptoms in
      schizophrenia.

PMID- 9176924
TI  - The functional significance of symptomatology and cognitive function in
      schizophrenia.
AB  - The relationships between positive and negative symptomatology, cognitive
      function, and the ability to perform basic activities of daily living in patients
      with schizophrenia were examined in two studies. In study 1, 112 medicated
      patients were assessed utilizing the Brief Psychiatric Rating Scale (positive
      symptoms), the Negative Symptom Assessment (negative symptoms and cognitive
      function), and the Functional Needs Assessment (activities of daily living).
      Study 2 (n = 41), utilized the same measures of symptomatology and added a
      comprehensive neuropsychological test battery. Regression analyses in both
      studies determined that symptomatology predicts a relatively small amount of the
      variance in the ability to perform basic activities of daily living. Cognitive
      function, whether assessed with the Cognition subscale of the Negative Symptom
      Assessment or a comprehensive neuropsychological test battery, predicted over 40%
      of the variance in scores on the Functional Needs Assessment. A path model in
      which cognition predicted both concurrent symptomatology and activities of daily
      living and where symptomatology had little direct impact upon activities of daily
      living fit the data. The importance of addressing cognitive deficits in
      psychosocial intervention programs is discussed.

PMID- 9176925
TI  - Non-selective impairment of Wisconsin Card Sorting Test performance in patients
      with schizophrenia.
AB  - Sixty-two schizophrenic patients and 26 healthy volunteers were administered the
      Wisconsin Card Sorting Test (WCST) a task putatively specific for frontal
      functions and the Wechsler Adult Intelligence Scale (WAIS). The purpose of this
      study was to evaluate the presence of specific frontal lobe deficits in the
      course of schizophrenia and the capacity of these tasks to discriminate between
      patients and controls. Schizophrenic patients showed a poorer performance than
      control subjects in both tests. No evidence emerged to support a higher
      discriminant power for the WCST in identifying schizophrenic subjects from
      healthy controls compared with the WAIS. Our data suggest that the deficit in
      WCST performance is not selective, but rather part of a more generalized
      neuropsychological impairment in schizophrenic patients.

PMID- 9176926
TI  - Language processing and memory in ill and well siblings from multiplex families
      affected with schizophrenia.
AB  - The present study was designed to extend the investigation of genetic factors for
      schizophrenia to cognitive and linguistic signs of central nervous system
      dysfunction. Of 51 siblings studied from 19 schizophrenia multiplex families, 37
      had a DSM-III-R diagnosis of schizophrenia or related schzophrenia spectrum
      disorder and 14 were well. Controls were 17 unrelated healthy individuals within
      the same social class and age range. Subjects were tested on measures of memory,
      attention, reading and expressive language ability. Schizophrenic and spectrum
      disorder siblings were significantly more impaired in tests of auditory
      discrimination and memory than their well siblings or controls and displayed
      significantly reduced syntactic complexity to their speech. While well siblings
      did not differ from controls on most measures, some aspects of language
      complexity were reduced. A familial effect was observed for tests of reading
      ability, attention, some syntactic measures, and short-term memory, although
      these were not the measures that distinguished patients from controls in this
      cohort, the scores were not correlated among the ill sibling pairs, and poorer
      scores did not segregate with schizophrenia within these families. Thus, while
      some measures of language, memory and attention are deviant in patients with
      schizophrenia, they may not be heritable and directly related to the genetics of
      the disorder. Instead, they may be a manifestation of, rather than a
      vulnerability to, the illness.

PMID- 9176927
TI  - Chronic haloperidol treatment does not affect structure of attention in
      schizophrenia.
AB  - Results of a number of investigations indicate attention is a multifactorial
      construct composed of four distinct cognitive factors including focus-execute,
      sustain, encode and shift abilities. While investigators have partially or fully
      replicated this attentional structure in a number of clinical and nonclinical
      populations, no study has adequately examined the structure of attention in
      patients with schizophrenia who are not treated with antipsychotics. In this
      study, we examined the four-factor theory of attention in patients with
      schizophrenia while they were stabilized on haloperidol (with no adjunctive
      antiparkinsonian/anticholinergic medications) and again when they were
      approximately 3 weeks drug free. Standard neuropsychological measures were used
      to assess attentional functions. Principal components analyses (varimax rotation)
      of neuropsychological test scores in medicated and drug-free conditions indicated
      that four factors accounted for 84.2 and 91.8 of total variance in medicated and
      unmedicated conditions, respectively. Based on these results, it appears that:
      (1) haloperidol does not appreciably affect structure of the attentional system
      in patients with schizophrenia; (2) unmedicated patients with schizophrenia
      exhibit a similar structure of attention as both medicated patients and controls,
      suggesting that attentional structure is 'normal' in schizophrenia; and (3) the
      four-factor attention theory is a useful and valid paradigm for evaluating
      attention in patients with schizophrenia, regardless of medication status.

PMID- 9176928
TI  - Metabolites of the antipsychotic agent clozapine inhibit the replication of human
      immunodeficiency virus type 1.
AB  - Schizophrenia is a serious and often debilitating neuropsychiatric disease of
      worldwide importance. Current therapy relies on the use of typical antipsychotic
      medications, which specifically inhibit binding of ligand at the D2 dopamine
      receptor, and atypical medications which display little activity for this
      receptor interaction. While atypical antipsychotic agents have been shown to
      variably inhibit other neuroreceptor-ligand interactions, the exact mechanisms
      for the therapeutic efficacy of these medications have not been completely
      defined. Clozapine, an atypical antipsychotic, and nine of its metabolites were
      studied in vitro for possible antiviral activity against a model of a human
      neurotropic virus, human immunodeficiency virus type 1 (HIV-1). In an assay for
      inhibition of virus-induced cytopathic effect (CPE) two metabolites demonstrated
      antiviral activity (ID50 = 37-85 micrograms/ml) (119-289 microM), while other
      atypical or novel antipsychotics as well as typical medications had no effect.
      Based on an ELISA, four chemically similar metabolites inhibited the production
      of p24, the major internal antigen of HIV (ID50 = 11.6-15.7 micrograms/ml) (38-51
      microM). These data suggest that the therapeutic efficacy of some antipsychotics
      may be due in part to an ability to inhibit viral replication. Antiviral agents
      may prove to be effective adjuncts in the treatment of schizophrenia.

PMID- 9176929
TI  - Relationship between negative symptoms in chronic schizophrenia and neuroleptic
      dose, plasma levels and side effects.
AB  - The negative symptoms of schizophrenia are often difficult to distinguish from
      the side effects of antipsychotic medication. In this study, we tried to clarify
      this issue by studying a group of patients in a clinic setting where a wide range
      of antipsychotic doses were being prescribed. Thirty-one patients meeting DSM-III
      R criteria for schizophrenia or schizoaffective disorder were studied. Clinical
      ratings were carried out to assess the positive and negative symptoms of
      schizophrenia, parkinsonism, akathisia and tardive dyskinesia. Plasma levels were
      also measured for the majority of patients. Antipsychotic plasma levels were
      found to be highly correlated with dose. Antipsychotic dose and plasma levels
      were not correlated with the severity of negative symptoms, akathisia or
      parkinsonism. However, the severity of positive symptoms and tardive dyskinesia
      were positively correlated with both dose and plasma level. These findings do not
      support the hypothesis that higher doses of antipsychotic medication are
      associated with more severe negative symptoms.

PMID- 9176930
TI  - Inter-hemispheric conflict theory of mind for schizophrenia.

PMID- 9176931
TI  - Re: "Small head circumference at birth in schizophrenia" (Kunugi et al.,
      Schizophrenia Research 20 (1996) 165-170)

PMID- 9176932
TI  - Visualization of residual anisotropic interactions in crosslinked natural rubbers
      by dipolar local field measurements and 2H natural abundance NMR spectroscopy.
AB  - An extension of the exploitation of indirect observation of 1H nuclei through 13C
      resonances is presented in the case of crosslinked elastomers. It is demonstrated
      that, by using this method in vulcanized elastomers above Tg, a direct
      visualization of residual dipolar interactions on different functional groups as
      well as their dependence on motional constraints is available. It is also shown
      that 2H natural abundance NMR spectra of elastomers provide similar information
      on motional constraints by way of residual quadrupolar interactions.

PMID- 9176933
TI  - 1H MAS and 1H[23Na] double resonance NMR studies on the modification of surface
      hydroxyl groups of gamma-alumina by sodium.
AB  - The modification of surface hydroxyl groups with sodium in a series of Na2CO3
      gamma-Al2O3 catalysts was investigated as a function of both the Na2CO3 loading
      and the calcination temperature by means of 1H magic angle spinning (MAS) and
      1H(23Na) spin-echo double resonance NMR techniques. The 1H NMR experiments
      revealed that sodium ions are homogeneously distributed over the alumina surface
      and closely coordinated with the surface hydroxyl groups. In the catalysts
      calcined at 250 degrees C, the acidic hydroxyl groups (with a chemical shift of
      2.0 ppm) are preferentially associated with sodium ions at low Na2CO3 coverages
      (5 and 10%), while both the acidic and the basic (0 ppm) hydroxyl groups are
      accessible for sodium ions at high coverages (15 and 20%). The coordination
      causes a low-field shift of about 2 ppm in the 1H MAS spectra, and a broad signal
      at 4.5 ppm appears. It is interesting that the 4.5 ppm signal is completely
      suppressed in the 1H(23Na) MAS experiments, providing direct evidence that a
      strong interaction exists between adsorbed sodium ions and the surface hydroxyl
      groups. Increasing the calcination temperature to 450 degrees C results in
      preferential removal of the acidic hydroxyl groups, and only the most basic
      hydroxyl groups remain when the calcination temperature is raised to 600 degrees
      C. This is attributed to the formation of the coordinated species. [formula: see
      text] which enhances the acidity of the surface hydroxyl groups and prompts their
      dehydroxylation, especially at high calcination temperature. Correlation of the
      1H MAS NMR results and catalytic activity measurements indicates that the basic
      hydroxyl groups are essential for the carbonyl sulfide hydrolysis reaction.

PMID- 9176934
TI  - Measurement of spin-lattice relaxation times of 13C in organic solids.
AB  - A transient nuclear Overhauser effect (NOE) makes measurements of the 13C spin
      lattice relaxation times in organic solids complicated. Extended Solomon
      equations are applied in order to describe 13C spin-lattice relaxation with 1H
      r.f. field irradiation. Spin-lattice relaxation under r.f. irradiation is shown
      to be generally a triple-exponential process, but it can be reduced to be single
      exponential under stronger r.f. field irradiation as well as in the absence of 1H
      initial magnetizations. Based on numerical calculations, the difference between
      spin-lattice relaxation curves obeying T1C < T1H and those obeying T1C > T1H is
      clearly indicated. The methyl group resonances in solid-state L-valine are
      examined, and the experimental results agree well with the theoretical results.

PMID- 9176935
TI  - Orientational alignment in solids from bidimensional isotropic-anisotropic
      nuclear magnetic resonance spectroscopy: applications to the analysis of aramide
      fibers.
AB  - The use of two-dimensional isotropic-anisotropic correlation spectroscopy for the
      analysis of orientational alignment in solids is presented. The theoretical
      background and advantages of this natural-abundance 13C NMR method of measurement
      are discussed, and demonstrated with a series of powder and single-crystal
      variable-angle correlation spectroscopy (VACSY) experiments on model systems. The
      technique is subsequently employed to analyze the orientational distributions of
      three polymer fibers: Kevlar 29, Kevlar 49 and Kevlar 149. Using complementary
      two-dimensional NMR data recorded on synthetic samples of poly(p
      phenyleneterephthalamide), the precursor of Kevlar, it was found that these
      commercial fibers possess molecules distributed over a very narrow orientational
      range with respect to the macroscopic director. The widths measured for these
      director distribution arrangements were (12 +/- 1.5) degrees for Kevlar 29, (15
      +/- 1.5) degrees for Kevlar 49, and (8 +/- 1.5) degrees for Kevlar 149. These
      figures compare well with previous results obtained for non-commercial fiber
      samples derived from the same polymer.

PMID- 9176936
TI  - Local and global dynamics in the glass-forming di-isobutyl phthalate as studied
      by 1H NMR.
AB  - Spin-lattice relaxation times T1 and T1p as well as 1H NMR spectra have been
      employed to study the dynamics of the glass-forming di-isobutyl phthalate in the
      temperature range extending from 100 K, through the glass transition temperature
      Tg, up to 340 K. Below Tg NMR relaxation is governed by local dynamics and may be
      attributed to rotation of methyl groups at low temperatures and to motion of
      isobutyl groups in the intermediate temperature interval. Above Tg the main
      relaxation mechanism is provided by overall molecular motion. The observed
      relaxation behavior is explained by motional models assuming asymmetrical
      distributions of correlation times. The motional parameters obtained from
      Davidson-Cole distribution, which yields the best fit of the data at all
      temperatures are given.

PMID- 9176937
TI  - Solid-state variable-temperature 1H MAS NMR studies on deuterated polyethylene.
AB  - Solid-state variable-temperature/magic angle spinning (VT/MAS) 1H NMR
      measurements were carried out on deuterated polyethylene. From these experimental
      results it was found that the 1H chemical shift induced by conformational and
      morphological changes of the polyethylene sample is within the linewidth of
      approximately 0.5 ppm. Furthermore, from MAS/dipolar decoupling experiments it
      was found that the resonance frequency of the proton varies linearly with the
      inverse square of the deuterium decoupling power. This experimental finding is
      discussed theoretically.

PMID- 9176938
TI  - Multiple-quantum magic-angle spinning NMR with cross-polarization: spectral
      editing of high-resolution spectra of quadrupolar nuclei.
AB  - An experiment is presented that combines the multiple-quantum magic-angle
      spinning (MQMAS) technique with cross-polarization (CP). As a preliminary test of
      this new method, we measured and compared the 27Al 3QMAS and 19F-->27Al CP 3QMAS
      spectra of a fluorinated AlPO4 aluminophosphate. Complete discrimination between
      the fluorinated and nonfluorinated Al sites was easily achieved, which
      demonstrates the usefulness of CP MQMAS for spectral editing. Future applications
      of this experiment will include other spin pairs and heteronuclear correlation
      NMR spectroscopy.

PMID- 9176939
TI  - Determining temperature in a magic-angle spinning probe using the temperature
      dependence of the isotropic chemical shift of lead nitrate.
AB  - The calibration of temperature in a magic-angle spinning probe with lead nitrate
      is discussed. The effects of rotation frequency on temperature are demonstrated.

PMID- 9176940
TI  - High refresh rate and oculomotor adaptation facilitate reading from video
      displays.
AB  - Reading from a video display terminal (VDT) was tested at screen refresh rates of
      500 Hz and 60 Hz. Reading was initially 8 words/min (3.05%) faster at 500 Hz. A
      hypothesis that reading rate on VDTs is limited by stimulus availability accounts
      for the difference. When the eye reaches a new fixation position, it 'parks'
      until a sample of text appears at the fovea. Then processing resumes in the
      normal way. This idea, combined with the 500-Hz reading data, can predict reading
      rate at any refresh rate, and is quantitatively confirmed by the reading rate at
      60 Hz. The difference in reading rates disappeared for the second half of the
      text, as a result of differences between frequencies of eye movements in the two
      refresh conditions. From the first half to the second, subjects at 60 Hz made
      more large forward saccades and fewer small reverse saccades. Both changes make
      sampling of the text more sparse, compensating for the dead time between samples.
      Subjects were unaware of refresh conditions, differences in their reading rates,
      and types of eye movements they generated. Reading from a continuously
      illuminated active-matrix display is slightly faster than from a comparable VDT.

PMID- 9176941
TI  - P31 phosphor persistence at photopic mean luminance level.
AB  - P31 phosphor screens are frequently used for short-term presentation of dot and
      grating patterns, but experimental data obtained with this technique have been
      criticized because of possible parasitic effects of phosphor persistence on
      subjects visual performance. Recently, this issue provoked a controversial
      discussion in Vision Research (Groner et al., 1993; Westheimer, 1993, 1994;
      Irwin, 1994; Di Lollo et al., 1994) which was concerned with persistence effects
      of P31 screens for dot patterns. Supplementing this discussion, the present work
      deals with the effects of different types of patterns (dot pattern vs. gratings)
      and background mean-luminance levels (scotopic vs. phototopic) on phosphor
      persistence. Physical measurements of P31 persistence occurring with grating
      patterns of a mean luminance of 20 cd m-2 (i.e. photopic range) were obtained by
      using an extremely linear photometer with high temporal resolution. Under this
      photopic condition, the measurements demonstrate a fast decay of residual grating
      contrast to 1.4% of its original value within 50 ms after pattern offset. This
      phosphor behavior must be considered when designing an experiment with a P31
      screen though it certainly embodies no problems in many applications.

PMID- 9176942
TI  - A pixel-resolution video switcher for eye-contingent display changes.
AB  - Moving-mask and moving-window paradigms are used to study the spatial and
      temporal aspects of visual information processing. Due to technical limitations,
      these paradigms have frequently been applied to reading, but only rarely to scene
      perception. Existing moving-mask or moving-window techniques for graphical
      stimuli usually blank the display inside or outside a square window,
      respectively. A new moving-window technique is presented here that uses a purpose
      designed video switcher and three synchronized video boards. The first video
      board contains the stimulus presented inside the window. The second video board
      contains the stimulus to be presented outside the window. The third video board
      contains a black-and-white image of the window that is used as a key signal for
      the video switcher. The video switcher selects between the video signals of the
      first and the second video board on a pixel-by-pixel basis, controlled by the key
      signal generated by the third video board. By panning the image of the third
      video board, the window can be moved very rapidly. Here we use oval windows,
      centered on the fixation spot as measured by an eye-tracker. The normal stimulus
      is visible inside the window, whereas manipulated information is presented
      outside the window, or vice versa.

PMID- 9176943
TI  - Characteristics of the Sony Multiscan 17se Trinitron color graphic display.
AB  - Technical measurements of the Sony Multiscan 17se were made and are reported in
      the belief that they would be useful to visual scientists who consider employing
      this device as a display unit. Luminance, spatial uniformity, luminance
      additivity between the output of the guns, CIE1931 chromaticity coordinates, and
      gamma correction parameters were measured. The characteristics of individual
      monitors will probably be different from the one studied here but it is believed
      that the results obtained serve as a fair indication of what might be expected
      from this device.

PMID- 9176944
TI  - Phosphor persistence of oscilloscopic displays: a comparison of four phosphors.
AB  - The period for which phosphor decay remains visible after stimulus offset was
      assessed for four phosphors commonly used in psychophysical experiments: P4, P15,
      P31, and P46. Stimuli were displayed behind closed shutters which opened at
      various intervals after stimulus offset. Thus, the observers' responses were
      based solely on the visibility of phosphor persistence. We varied viewing
      conditions (dark-adapted vs. veiling light), type of task (detection vs.
      identification), and intensity of the stimuli. No detectable persistence was ever
      produced by the P15 phosphor. In contrast, the P31 phosphor remained visible for
      several hundred ms. even with a veiling light. The P4 and P46 phosphors produced
      persistence of intermediate durations. It is concluded that P15 is the phosphor
      of choice for visual experiments.

PMID- 9176945
TI  - An introduction to accurate display timing for PCs under 'Windows'.
AB  - As the use of computers for delivering stimuli in vision research has become
      ubiquitous, there is an obvious need for accurate timing of display monitors
      without the use of expensive hardware extensions. If a user should decide to
      program an application in the increasingly common 'Windows' operating system for
      IBM PCs and compatibles, a software solution for this problem is not obvious any
      more. The goal is to achieve display durations down to one single video frame.
      This article describes several approaches and a tested solution designed to run
      on any PC or compatible under Windows 3.1/95, regardless of the video card used.
      This creates new possibilities for low-cost, implementation of visual experiments
      for laboratory and classroom use.

PMID- 9176946
TI  - Colour bit-stealing to enhance the luminance resolution of digital displays on a
      single pixel basis.
AB  - A look-up table algorithm is described for enhancing the luminance resolution at
      the expense of the colour resolution in digital displays of colour images. For
      colour displays with a look-up table resolution of 8 bits/gun, the algorithm
      provides a luminance resolution of 11-12 bits without loss of spatial or temporal
      resolution. This improvement can reduce the minimum luminance step in the mid
      luminance range from 1.5% to > 0.2% with no additional hardware.

PMID- 9176947
TI  - Selective stimulation of colour mechanisms: an empirical perspective.
AB  - Anatomically distinct parvo and magno visual pathways show considerable
      functional overlap. However, specific stimulation of the most sensitive colour
      opponent parvo-neurones is still possible, provided that colour stimuli are
      verified for selectivity. The authors have shown that gratings of low contrast,
      low spatial frequency and of restricted spatial content (6 or less spatial
      cycles) are optimal stimuli for distinguishing between colour-related (tritan and
      red/green) from achromatic or partly chromatic responses. This is particularly
      important when recording global responses, such as visual evoked potentials,
      VEPs. The crucial point is that at low presentation rates (< 2 Hz), colour
      related onset VEPs are maximally different from contrast reversal VEPs, thereby
      reflecting the activity of sustained-type parvo mechanisms. Achromatic onset,
      offset and reversal VEPs are similar, reflecting mediation by transient-type
      magno mechanisms. A stringent test of colour-response specificity is to check
      whether the chromatic reversal VEP has a low-pass temporal tuning curve, since it
      becomes band-pass when substantial achromatic intrusions are present.
      Specification of chromatic isoluminant stimuli, e.g. along cardinal axes, does
      not guarantee their colour-selectivity, if chromatic aberration and variable
      macular pigmentation changes the chromatic content of the retinal image. It is
      shown here how chromatic stimuli, namely (1) red/green and (2) purple/green
      (tritanopic) gratings, can be optimized for selective stimulation of the colour
      system.

PMID- 9176948
TI  - Raster-scan cathode-ray tubes for vision research--limits of resolution in space,
      time and intensity, and some solutions.
AB  - Raster-based cathode-ray tubes (CRTs) are increasingly used for stimulus
      presentation. While very flexible, their design based on consumer electronics can
      limit their value in vision research. Here their limitations of resolution in
      time, space, intensity and wavelength are systematically compiled. Often,
      ingenious ideas can circumvent such limitations for specific experiments. Some ad
      hoc solutions, as well as the more general techniques of dithering and anti
      aliasing, are presented.

PMID- 9176949
TI  - A display controller for very brief image presentations.
AB  - The device described is a digital interface between a laboratory computer and a
      point-plotting oscilloscopic display. The combination of computer, display, and
      interface gives high spatial resolution and exceptionally low frame durations.
      This system is a powerful tool for studying the time-domain properties of visual
      perception.

PMID- 9176950
TI  - Dots & Pixels: a C++ library for the display of random dot patterns.

PMID- 9176951
TI  - XPIP 2.2: X Portable Interface Package.
AB  - Psychophysical researchers often need to vary stimuli parametrically during
      experimental design. The X Portable Interface Package, a set of free software
      libraries for X-Windows, provides a suitable platform for quickly prototyping
      visual stimuli and administering simple experiments.

PMID- 9176952
TI  - The Psychophysics Toolbox.
AB  - The Psychophysics Toolbox is a software package that supports visual
      psychophysics. Its routines provide an interface between a high-level interpreted
      language (MATLAB on the Macintosh) and the video display hardware. A set of
      example programs is included with the Toolbox distribution.

PMID- 9176953
TI  - The VideoToolbox software for visual psychophysics: transforming numbers into
      movies.
AB  - The VideoToolbox is a free collection of two hundred C subroutines for Macintosh
      computers that calibrates and controls the computer-display interface to create
      accurately specified visual stimuli. High-level platform-independent languages
      like MATLAB are best for creating the numbers that describe the desired images.
      Low-level, computer-specific VideoToolbox routines control the hardware that
      transforms those numbers into a movie. Transcending the particular computer and
      language, we discuss the nature of the computer-display interface, and how to
      calibrate and control it.

PMID- 9176954
TI  - Pixel independence: measuring spatial interactions on a CRT display.
AB  - The standard working assumption of careful CRT imaging is that each pixel is
      imaged independently, through a point nonlinearity (the monitor's gamma function,
      relating screen luminance to input voltage), and then blurred by the point-spread
      function of the beam spot on the phosphor. Unfortunately most monitors have
      inadequate video bandwidth, DC restoration, and high-voltage regulation to live
      up to this ideal model. Two tests are recommended for assessing a CRT's deviation
      from the pixel-independence model.

PMID- 9176955
TI  - Psychophysica: Mathematica notebooks for psychophysical experiments (cinematica-
      psychometrica--quest).
AB  - Psychophysica is a set of software tools for psychophysical research. Functions
      are provided for calibrated visual displays, for fitting and plotting of
      psychometric functions, and for the QUEST adaptive staircase procedure. The
      functions are written in the Mathematica programming language.

PMID- 9176956
TI  - PXL: a library for psychological experiments on IBM PC type computers.
AB  - PXL is a library for the procedural control of experiments which also provides
      many high-level utility functions. A collection of standard experiments with
      source codes is available.

PMID- 9176957
TI  - The use of VisionWorks in visual psychophysics research.
AB  - We describe the VisionWorks system-an integrated hardware and software experiment
      work-station for visual psychophysics and neurophysiology. While the system
      already incorporates a large variety of stimuli and psychophysical methods, it is
      continually being updated to meet the ever-changing needs of vision researchers.

PMID- 9176958
TI  - The Morphonome image psychophysics software and a calibrator for Macintosh
      systems.
AB  - Software for measurement of psychophysical thresholds with 2D moving and coloured
      images is described. It is menu-driven and has contrast resolution to 0.2%
      without hardware modifications. A calibrator to provide the full calibration of
      the Macintosh monitor required by the software is also described.

PMID- 9176959
TI  - A note on luminance calibration of raster-scan cathode-ray tubes: temporal
      resolution, ripple, and accuracy.
AB  - Accurate luminance calibration is an important issue for stimuli in vision
      research. Raster-scan cathode-ray tubes present a rapidly scanning spot with a
      luminance of the order of 10,000 cd m-2 (the actual value depends on video timing
      and phosphor persistence). With little spatial integration this may result in
      overloading of the front stage of a photometer. More importantly, even if
      averaged over hundreds of milliseconds, the pulsed nature of the luminance signal
      will markedly reduce accuracy of the luminance measurement. A frame-synchronised
      photometer is described to increase measurement accuracy whilst still rapidly
      acquiring the result.

PMID- 9176960
TI  - FORPXL--a Fortran interface to PXL, the Psychological Experiments Library.

PMID- 9176961
TI  - R_Contrast: rapid measurement of recognition contrast thresholds.

PMID- 9176962
TI  - Programs for diagnosis and therapy of visual field deficits in vision
      rehabilitation.

PMID- 9176963
TI  - How safe are central venous catheters?

PMID- 9176964
TI  - Supportive care of cancer patients in Dubai.
AB  - Supportive care of cancer patients starts from the first day of diagnosis. It is
      a comprehensive approach involving psychosocial, physical and spiritual supports.
      Maximum efforts are put in to keep the patients as comfortable as possible during
      diagnosis, during treatment and during the terminal stages of their disease.

PMID- 9176965
TI  - Should bisphosphonates be standard therapy for bone pain?
AB  - We have been studying bisphosphonates since the early 1980s, initially
      investigating etidronate in the management of hypercalcaemia and, since the mid
      1980s, clodronate in the management of hypercalcaemia, bone pain, and skeletal
      complications in patients with bone metastases. We have also recently reported
      that bone metastases can be prevented or delayed in patients without evidence of
      bone disease but with recurrent disease at other sites. Bisphosphonates are now
      the standard therapy for hypercalcaemia after rehydration. For patients with bone
      metastases and bone pain, a trial of clodronate 600-1500 mg i.v. in 500 ml normal
      saline over 3 h given every 1-2 weeks is worth-while in association with other
      modalities such as radiotherapy and analgesic medications. Oral clodronate or
      intravenous pamidronate should be given as a preventive measure in patients with
      established bone metastases from breast cancer and myeloma. In patients with no
      evidence of bone metastases, it may be that bisphosphonates can delay the
      emergence of bone metastases; at present this remains under clinical
      investigation and our pioneer trials require confirmation. Clinical trials of
      bisphosphonates in the treatment of hypercalcaemia, bone pain, management of
      patients with bone metastases and management of patients with recurrent cancer
      but no evidence of bone metastases will be discussed.

PMID- 9176966
TI  - When to treat dehydration in a terminally ill patient?
AB  - The need to treat dehydration in terminally ill patients has become a very
      controversial topic. Numerous reports in the literature illustrate opposing view
      points from both clinical and ethical perspectives. Arguments for the maintenance
      of hydration in terminally ill patients have tended to come from "the traditional
      medical model". Many health care professionals looking after terminally ill
      patients have reacted to the generalized use of intravenous fluids in dying
      patients and the perceived negative effects of this management. Our palliative
      care group has argued that the viewpoint that dehydration in dying patients is
      not a cause of symptom distress overlooks commonly reported problems, such as
      agitated delirium, that can be prevented or reversed by the management of
      dehydration. This review presents a summary of the traditional arguments, a
      different perspective on the controversy, biochemical parameters reported in
      terminally ill cancer patients, recent dehydration research, and the use of
      hypodermoclysis and rectal hydration. We conclude that the data reported to date
      are insufficient to allow a final conclusion on the benefit or harm of
      dehydration in terminally ill patients. Nevertheless, it is worth considering
      that while some dying patients may not suffer any ill effects from dehydration,
      there may be others who do manifest symptoms, such as confusion or opioid
      toxicity, that might be alleviated or prevented by parenteral hydration.

PMID- 9176967
TI  - The relationship between parameters of serotonin metabolism and emetogenic
      potential of platinum-based chemotherapy regimens.
AB  - Evaluation of the relationship between parameters of serotonin (5-HT) metabolism
      and emesis in platinum-based chemotherapy. Female patients receiving
      chemotherapies containing either cisplatin (35 patients; 80 courses) or
      carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and
      measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite
      of 5-HT, was performed over 3 days. Comparisons were performed for single-agent
      cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose
      DDP (> or = 75 mg/m2) versus high-dose DDP combined with cyclophosphamide, high
      dose versus low-dose DDP (< or = 50 mg/m2), and single-agent CBDCA versus a
      combination with alkylating agents. Cisplatin induced both a significantly higher
      frequency of emesis and a significantly higher increase of 5-HIAA excretion than
      carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic
      potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion
      induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a
      higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on
      day 1. No significant difference was found when single-agent cisplatin was
      compared with cisplatin combined with cyclophosphamide. In contrast, a
      combination of carboplatin with alkylating agents induced a larger increase in
      urinary 5-HIAA and showed a higher emetogenic potential than single-agent
      carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination
      therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide
      evidence for a relationship between emetogenic potential and patterns of 5-HIAA
      excretion following platinum-based chemotherapy.

PMID- 9176968
TI  - Oral dolasetron mesilate (MDL 73,147EF) for the control of emesis during
      fractionated total-body irradiation and high-dose cyclophosphamide in patients
      undergoing allogeneic bone marrow transplantation.
AB  - The purpose of the present study was to evaluate the efficacy and safety of oral
      dolasetron mesilate in the prevention of nausea and vomiting that might otherwise
      be induced by total-body irradiation (TBI) and high-dose cyclophosphamide. In an
      open non-comparative study 20 patients who received TBI for 3 days and high-dose
      cyclophosphamide chemotherapy for 2 days as part of their preparation for bone
      marrow transplantation were given oral dolasetron mesilate at dosages ranging
      from 50 to 200 mg 1 h before each fraction of radiotherapy and cyclophosphamide
      administration. Initial rescue therapy consisted of intravenous dolasetron
      mesilate. If nausea and vomiting remained uncontrolled, standard antiemetics were
      to be used. Of the 20 patients, 13 had only two emetic episodes or fewer in the 3
      day TBI period. On days 1 and 2 of cyclophosphamide administration, 11 and 6
      patients had fewer than two emetic episodes. From day 1 to day 3, 15 patients
      experienced no nausea or only mild nausea, and on the days of chemotherapy 8 and
      7 patients had mild nausea or none at all. Rescue with i.v. dolasetron mesilate
      was needed by 3 and 6 patients during the TBI and the chemotherapy periods
      respectively. In 2 patients additional antiemetics were used on days 2-3 and 4-5.
      Mild to moderate headache was reported in 6 patients. No unexpected abnormalities
      were observed in haematology, biochemistry or urinalysis, and vital signs were
      unaffected throughout the study period. The data suggest that oral dolasetron
      mesilate is effective and safe for the prevention of nausea and vomiting during
      TBI and cyclophosphamide chemotherapy prior to bone marrow transplantation.
      Future controlled studies should evaluate combination antiemetic therapy with
      dolasetron mesilate for this indication.

PMID- 9176969
TI  - Complications associated with central venous catheters used for the collection of
      peripheral blood progenitor cells to support high-dose chemotherapy and
      autologous stem cell rescue.
AB  - The purpose of this study was to review the incidence and type of complications
      associated with the insertion and use of central venous catheters for
      leukapheresis and high-dose chemotherapy with stem cell rescue. One hundred sixty
      seven central venous catheters placed either at the transplant center or by
      various community surgeons were studied for insertion complications, inability to
      perform leukapheresis and incidence of infection. The overall incidence of hemo-
      or pneumothorax was 3.6%. Inability to pherese occurred in 13% of catheters
      placed by outside surgeons and 6.5% of catheters inserted at the transplant
      institution. Most often, these were due to malposition of the catheter too high
      in the superior vena cava or in other veins. Deep venous thrombosis was often
      related to this malposition and occurred in 4.8% of all patients. Pulmonary
      embolism was not seen in these patients despite the fact the catheters were often
      left in place during the thrombotic episode. Early or late-onset infections
      occurred in 6.5% of patients and were most often exit site infections. The
      incidence of complications of pheresis catheters is high but might be reduced by
      more attention to proper placement of the catheter closer to the right
      atrial/superior vena cava junction, and limiting insertion to a cadre of surgeons
      familiar with leukapheresis requirements.

PMID- 9176971
TI  - Epidemiology of infections in the adult medical intensive care unit of a cancer
      hospital.
AB  - A prospective collection of positive antimicrobial cultures was performed over 12
      consecutive months in the medical intensive care unit of a cancer hospital. In
      all, 144 infections and 163 pathogens were documented during 87 of the 528
      admissions. Lung, urinary, ENT (ear, nose and throat) infections and bacteraemia
      were the most frequently documented. Staphylococcus species, Streptococcus
      species, Escherichia coli, Klebsiella species and Pseudomonas species were the
      most common pathogens. Gram-positive strains were observed predominantly during
      monomicrobial bacteraemia (48.9%). Methicillin-resistant Staphylococcus aureus
      (MRSA) and Staphylococcus epidermidis (MRSE) were found in 58% and 92% of the
      isolated strains respectively. No particular outbreak was identified. A further
      prospective study will be necessary to evaluate the impact of the antibiotic use
      on the selection of resistant strains in our ICU.

PMID- 9176970
TI  - Mechanical and infective central venous catheter-related complications: a
      prospective non-randomized study using Hickman and Groshong catheters in children
      with hematological malignancies.
AB  - The aim of this study was to compare the Hickman and Groshong central venous
      catheters (CVCs) for incidence and severity of catheter-related complications in
      children. Seventy-three patients with hematological malignancies were observed,
      42 with Groshong CVCs and 31 with Hickman CVCs. The number of infective episodes
      per 100 CVC-days was not significantly different (0.25 in the Hickman group
      versus 0.13 in the Groshong group; P = 0.24). The most frequent type of CVC
      related infection in both groups was microbiologically documented sepsis; in most
      cases Gram-positive bacteria were isolated. Neutropenia (P < 0.001 for both CVCs)
      and hospital CVC management (P = 0.0047 for the Hickman group, P < 0.001 for the
      Groshong group) emerged as the major risk factors for the outbreak of infections.
      The rate of mechanical complication episodes per 100 CVC-days was similar in both
      groups (1.01 in the Hickman group versus 1.1 in the Groshong group: P = 0.58).
      Some complications (fissures, ruptures, total lumen obstruction by clots)
      occurred only in the Groshong group. Our study did not demonstrate any
      statistically significant difference in the incidence of mechanical and infective
      CVC-related complications between these two types of catheter.

PMID- 9176972
TI  - Relationship between quality of life and mood in long-term survivors of breast
      cancer treated with mastectomy.
AB  - This study sought to compare the mood and quality of life (QOL) of breast cancer
      survivors with those observed in low-risk breast cancer screening patients. A
      group of long-term stage I-III breast cancer survivors (n = 60) was compared with
      low-risk breast cancer screening patients (n = 93) on measures of depression,
      anxiety, and QOL. Patients without a previous psychiatric history were studied.
      Although the groups differed in age and education, correlations performed between
      age, education, and the outcome measures showed no association of age and
      education with the outcome measures. Breast cancer patients with stage III
      disease showed significantly poorer functioning, in all areas except family than
      did other breast cancer patients; however, when compared with the breast cancer
      screening group, they showed higher QOL scores in several domains. Higher mood
      scores were correlated with poorer scores in all QOL areas except family
      functioning in the breast cancer group. Only significantly elevated depression
      scores correlated with poorer QOL areas in the breast cancer screening group. The
      psychological measures were found to be more robust predictors of QOL than the
      demographic variables in both the cancer and the screening patients. These
      results suggest that long-term survivors of breast cancer continue to experience
      significant stress and emotional distress, as evidenced by increased depression
      and lower QOL functioning.

PMID- 9176973
TI  - Candidemia in acute leukemia patients.
AB  - Fungal infections are an important cause of morbidity and mortality in patients
      with acute leukemia (AL). Candidemia, once rare, is now a common nosocomial
      infection because of the intensity of chemotherapy, prolonged neutropenia,
      administration of broad-spectrum antibiotics and use of central venous catheters
      (CVC). We retrospectively identified patients treated for AL from 6/86 to 6/95
      who also had candidemia. We describe 28 patients (incidence 6.3%) with a median
      age of 39 years, 24 of whom were on remission induction and 4 on postremission
      chemotherapy. All patients had CVC and empiric antimicrobial therapy, 4 had been
      given prophylactic antifungal drugs, and 2 had parenteral nutrition. Neutropenia
      was profound (median leukocyte nadir 200/microliters, median duration 19 days).
      Candida was isolated in blood cultures 10 days (median) after the start of
      neutropenia. The clinical presentation included fever (100%), respiratory
      symptoms (71.4%), skin lesions (39.2%) and septic shock (17.8%). Amphotericin B
      was given to 17 patients and liposomal amphotericin to 5 patients. Infection
      resolved in 18 patients (64.2%). 10 of whom were in complete remission. Mortality
      from candidemia was 17.8% (5/28). In conclusion, fungal infections are
      responsible for death in a significant number of patients. In our series
      treatment success was related to its rapid onset and to the recovery of
      neutropenia.

PMID- 9176974
TI  - Matching the clinical function and symptom status with the expectations of
      patients with advanced cancer, their families, and health care workers.
AB  - Continuous accurate assessment is mandatory for palliative care of good quality.
      One of the major objectives in palliation is to meet the expectations of patient,
      family members and care givers. While a number of valid tools for assessing
      symptoms or function are available, there are unfortunately no recognized
      instruments for assessing expectations. The mismatch of expectations and the
      actual situation is a major source of distress and conflict. The present paper
      describes a simple way of visualizing this distress and conflict graphically. In
      our experience, this method is helpful in raising awareness of and enabling
      analysis of distress and conflict in patients, family members, and health care
      workers. It is also useful in the education of students and members of the
      palliative care team. It is illustrated with reference to four clinical
      situations.

PMID- 9176975
TI  - What should be the elements of any settlement with the tobacco industry?
AB  - Litigation and regulatory assaults on the tobacco companies may create a
      willingness among tobacco manufacturers to bargain resources and acceptance of
      public policy changes for limitations of liability, as has been seen by the
      recent settlement with the Liggett Group. Two elements absolutely critical to any
      plan are the elimination of tobacco advertising and promotion and the removal of
      addiction as a reason for tobacco use. Minimal components of any settlement
      should include: (a) acceptance by the tobacco manufacturers of the causal
      relationship between tobacco use and disease, and the addictive nature of
      nicotine; (b) a total ban on tobacco advertising and promotion; (c) FDA
      jurisdiction over tobacco products and their nicotine content, with the intent of
      removing nicotine as soon as acceptable nicotine substitution products are
      available; (d) reimbursement to the states for Medicaid and other state
      expenditures attributable to smoking, to the maximum extent feasible; (e) funding
      for local, state, and federal programmes and research in tobacco control; (f)
      acceptance of legislation and regulations protecting the right of non-smokers to
      breathe air free of tobacco smoke; (g) funding for a large, national, media-led,
      anti-tobacco campaign; and (h) cessation assistance for addicted smokers. If
      negotiations toward a settlement proceed, it is essential that the public health
      community participate in defining the elements of any agreement to ensure that
      whatever agreement develops is focused on reducing tobacco-related disease rather
      than continuing the profitability of American tobacco companies. That
      participation requires articulation of the core elements essential to an
      acceptable agreement. If resolution of the public health issues surrounding
      continued sale of tobacco products can be reached in the United States, it may
      provide a model for similar resolution in other countries.

PMID- 9176976
TI  - Tax and spend: a policy to help poor smokers.

PMID- 9176977
TI  - "The Marlboro Man.".

PMID- 9176978
TI  - Battling upstream against the tobacco epidemic in China.

PMID- 9176979
TI  - Bill gives hope that Turkey can fly.

PMID- 9176980
TI  - 1996: the year voters rejected the Marlboro Man.

PMID- 9176981
TI  - Poverty status and cigarette smoking prevalence and cessation in the United
      States, 1983-1993: the independent risk of being poor.
AB  - OBJECTIVE: To analyse the independent relations between poverty status and
      cigarette smoking prevalence and cessation in the United States, 1983-1993.
      DESIGN: An analysis of eight cross-sectional national surveys. SETTING: The
      United States, 1983-1993. PARTICIPANTS: 236,311 civilian, non-institutionalised
      adult residents of the United States, aged 18 years and older. MAIN OUTCOME
      MEASURES: Probability of current cigarette smoking and proportion of former
      smokers among ever-smokers (quit ratio) in surveyed subjects below the poverty
      threshold, compared with those at or above the poverty threshold. RESULTS: The
      odds ratio for current smoking among persons below the poverty threshold ranged
      from a low of 1.10 in 1985 to a high of 1.45 in 1990, and remained between 1.26
      and 1.30 during 1991-1993. The odds ratio for smoking cessation (quit ratio)
      among persons below the poverty threshold ranged from 0.81 in 1985 to 0.64 in
      1991, and remained between 0.73 and 0.66 during 1991-1993. These measures of the
      relations between poverty status and smoking were derived using multiple logistic
      regression models, which adjusted for the effects of sex, age, education, race,
      employment status, marital status, and geographic region. CONCLUSIONS: Persons
      below the poverty threshold continue to be more likely than those at or above the
      threshold both to be current smokers and not to have quit. Poverty may be an
      indicator of underparticipation in the changing social norms regarding smoking
      behaviour in recent years. Individuals below the poverty threshold may need
      focused efforts to help achieve the Healthy People 2000 objectives for reducing
      adult smoking prevalence. Further understanding of the relation between poverty
      and smoking is essential to develop effective programmes for this vulnerable
      population subgroup.

PMID- 9176982
TI  - Scientific quality of original research articles on environmental tobacco smoke.
AB  - OBJECTIVE: To evaluate the scientific quality of original research articles on
      the health effects of environmental tobacco smoke; to determine whether poor
      article quality is associated with publication in non-peer-reviewed symposium
      proceedings or with other article characteristics. DESIGN: Cross sectional study
      of original research articles on the health effects of environmental tobacco
      smoke published in peer reviewed journals and non-peer-reviewed symposium
      proceedings from 1980 to 1994. Article quality was assessed by two independent
      reviewers who used a valid and reliable instrument, were unaware of study
      hypotheses, were blinded to identifying characteristics of articles, and had no
      disclosed conflicts of interest. PARTICIPANTS: All symposium articles (n = 68)
      and a random sample of peer reviewed journal articles (n = 68) that satisfied
      inclusion/exclusion criteria. MAIN OUTCOME MEASURE: Mean quality scores, which
      could range from 0 (lowest quality) to 1 (highest quality). RESULTS: Using
      multivariate regression analysis, symposium articles were of poorer scientific
      quality than peer reviewed journal articles when controlling simultaneously for
      the effects of study design, article conclusion, article topic, and source of
      funding acknowledged (P = 0.027). Article quality was not associated with either
      source of funding acknowledged or article conclusion in multivariate analyses.
      CONCLUSIONS: In published reports on environmental tobacco smoke, non-peer
      reviewed symposium articles tend to be of poor quality. These articles should not
      be used in scientific, legal, or policy settings unless their quality has been
      independently assessed.

PMID- 9176983
TI  - Tobacco use among young adults in Norway, 1973-95: has the decrease levelled out?
AB  - OBJECTIVE: To describe the prevalence of tobacco use among young Norwegian
      adults, 1973-1995. DESIGN: Cross sectional personal and telephone surveys.
      SETTING: Norway, 1973-1995. PARTICIPANTS: Population based samples of Norwegians
      aged 16-74 years. RESULTS: A trend to a decline in tobacco use among young adult
      Norwegians during the 1960s and 1970s levelled out during the 1980s. Hence, the
      total prevalence of smoking in Norway decreased by only two percentage points
      from 1980 to 1993, as compared to approximately 10 percentage points in many
      other European countries. An increase in smoking prevalence (and in the use of
      snuff among males) in the age group 16-19 years has been observed in recent
      years. Thus smoking prevalence among young males and females in 1995 was
      comparable to that observed in the early 1980s. CONCLUSIONS: Trends in tobacco
      use reflect an underutilization of preventive measures in general, and health
      education measures in particular. Financial resources appropriated for health
      education and information were reduced by 90% during the 1980s.

PMID- 9176984
TI  - Release of carbon granules from cigarettes with charcoal filters.
AB  - OBJECTIVE: To inspect cigarettes with a triple granular filter for charcoal
      granules on the cut filter surface and, if present, to determine whether the
      charcoal granules on the filter are released during smoking. DESIGN: 400 Lark
      cigarettes in 20 packs were examined individually by each of three investigators
      for the presence of charcoal granules on the cut surface of the cellulose acetate
      filter. Without removing the cigarettes from the pack, the filters were examined
      with a stereo zoom microscope for charcoal granules. The percentage of cigarettes
      that had charcoal granules was defined, and charcoal granules on each filter were
      counted. Randomly selected cigarettes were then smoked by consenting adult
      smokers to assess whether the charcoal granules were released during smoking.
      Lark cigarettes were smoked with a conventional cigarette holder that had been
      configured to contain an in-line membrane. After smoking, the membrane was
      analysed microscopically for charcoal granules and other components of the filter
      that had been released during smoking. RESULTS: Charcoal granules were observed
      in 79.8% (319/400) of the cigarettes examined. The number of granules per
      cigarette was 3.3 (SD 3.7). Gaps between the tipping papers--the wrapping papers
      that surround the filter--were often seen (70%; 242 (71); n = 400 cigarettes).
      Further, the charcoal cavity was about 60% empty. For all smokers (n = 8/8),
      charcoal granules were released during smoking. The number of charcoal granules
      captured on the membranes was 22.5 (16.2) per cigarette. CONCLUSIONS: Charcoal
      granules are incorporated into cigarette filters to aid in removing toxins in
      cigarette smoke. In studies of Lark, a popular American cigarette with a charcoal
      filter, charcoal granules were observed on the filter surface, and were released
      from the filter when the cigarettes were smoked. During smoking, the toxin
      containing charcoal granules are inhaled or ingested. The specific adverse health
      effects of inhaling or ingesting carbon granules have not been addressed;
      nevertheless, the smoker, as an educated consumer, should be informed of the
      possible health risks.

PMID- 9176985
TI  - Political realities of statewide smoking legislation: the passage of California's
      Assembly Bill 13.
AB  - OBJECTIVE: To prepare a history of the enactment of California Assembly Bill 13
      (AB 13), a state law prohibiting smoking in most workplaces passed in 1994, and
      to discuss its initial impacts. METHODS: Data were gathered from open ended
      interviews with representatives of voluntary health organisations, local
      government organisations, and principal legislators involved in the process, as
      well as observers around the state who could provide insight into the legislative
      process. Information was also obtained from legislative hearings and debates,
      public documents, letters and personal communications, internal memoranda, and
      news reports. RESULTS: The success of local tobacco control legislation in
      California led to a situation in which some health groups were willing to accept
      state preemption in order to attract the support of the state restaurant
      association for a bill. The decision to accept this preemption compromise was
      made by the state level offices of the voluntary health agencies without
      consulting the broader tobacco control community within California. In contrast,
      local tobacco control advocates did not accept this compromise, in part because
      of their belief that local legislation was a better device to educate the public,
      generate media coverage, and build community support for enforcement and
      implementation of clean indoor air and other tobacco control laws. Enactment of
      AB 13 was associated with a slowing of all local tobacco control legislation,
      including youth oriented laws. CONCLUSIONS: Because its supporters initially
      doubted that AB 13 would pass, there was never an effort to reconcile the policy
      differences between state oriented and locally oriented tobacco control policies.
      This lack of consensus, combined with the political realities inherent in passing
      any state legislation, led to a bill with ambiguous preemption language which
      replaced the "patchwork of local laws" with a "patchwork of local enforcement."

PMID- 9176986
TI  - Those who live by the sword....

PMID- 9176987
TI  - Do men and women differ in exposure per cigarette?

PMID- 9176988
TI  - New legislation in Turkey.

PMID- 9176989
TI  - Alpha and beta phases of 4-aminoquinoline-2-carboxylic acid monohydrate.
AB  - The structures of two phases of the title compound, C10H8N2O2.H2O, are reported.
      While the organic molecule has very nearly the same molecular geometry in the two
      phases, the hydrogen-bonding patterns are quite different. In each case, however,
      a three-dimensional network of hydrogen bonds is formed. In the alpha phase, six
      N-H ... O hydrogen bonds have donor-acceptor distances ranging from 2.681 (2) to
      3.206 (2) A, while three O-H...O hydrogen bonds range from 2.837 (2) to 3.173 (2)
      A, and in the beta phase, four N-H ... O hydrogen bonds range from 2.668 (2) to
      3.038 (2) A, while two O-H...O hydrogen bonds are 2.951 (3) and 2.959 (3) A in
      length.

PMID- 9176990
TI  - Heterocyclic N-acetoxyarylamines, models for the putative ultimate carcinogens of
      aromatic amines: 2-acetoxyamino-5-phenylpyridine and 2-acetoxyaminopyridine.
AB  - The structures of O-acetyl-N-(5-phenyl-2-pyridyl)-hydroxylamine, C13H12N2O2, (I),
      and O-acetyl-N-(2-pyridyl)hydroxylamine, C7H8N2O2. (II), have been determined in
      order to confirm earlier structure assignments based on spectroscopic
      information. Compound (I) is the probable mutagenic metabolite of the
      phenylalanine pyrolysis product 2-amino-5-phenyl-pyridine. The crystal structures
      of (I) and (II) are the first reported for heterocyclic N-acetoxyarylamines, the
      corresponding homocyclic arylamine derivatives being extremely unstable. In the
      solid state, both (I) and (II) exist as hydrogen-bonded dimers, with the
      arylamine N atom acting as donor and the pyridine N atom of a neighboring
      inversion-related molecule as acceptor; the distance between donor and acceptor N
      atoms is 3.007(2) in (I) and 2.956(2) A in (II). This orientation of the N-H bond
      results in the rotation of the acetoxy group out of the plane of the pyridine
      ring by 22.5(2) in (I) and 27.4(2) degrees in (II).

PMID- 9176991
TI  - A mechanistic investigation of the microbial chiral inversion of 2
      phenylpropionic acid by Verticillium lecanii.
AB  - Previous investigations have described the development of nongrowing suspensions
      of Verticillium lecanii as a microbial model of the mammalian chiral inversion of
      the 2-arylpropionic acids (2-APAs). Mechanistic studies in mammals have shown
      that inversion involves loss of the alpha-methine proton but retention of the
      original atoms at the beta-methyl position, and a mechanism has been proposed
      involving enzymatic epimerisation of acyl-CoA thioester derivatives of the
      substrate. Inversion of the 2-APAs by V. lecanii exhibits extensive
      intersubstrate variation in the presence, rate, extent, and direction of
      inversion, which are different from those observed in mammalian systems, possibly
      indicating differences in the mechanism of inversion between mammalian and
      microbial cells. This study involved the investigation of proton/deuterium
      exchange by 1H-nuclear magnetic resonance following incubation of deuterated
      derivatives of 2-phenylpropionic acid (2-PPA), a model compound, in cell
      suspensions of V. lecanii and incubation of undeuterated 2-PPA in cell
      suspensions containing D2O. The results indicated that the inversion of 2-PPA by
      V. lecanii also involved exchange of the alpha-methine proton but complete
      retention of the original atoms at the beta-methyl position. No kinetic deuterium
      isotope effect was observed, indicating that loss of the alpha-methine proton is
      not the rate-limiting step of the inversion process. This suggests that the
      observed differences between microbial and mammalian systems probably involve the
      stereoselective acyl-CoA thioester formation step and not the subsequent
      epimerisation of the resultant diastereomers.

PMID- 9176992
TI  - AMPA receptor agonists: resolution, configurational assignment, and pharmacology
      of (+)-(S)- and (-)-(R)-2-amino-3-[3-hydroxy-5-(2-pyridyl)-isoxazol-4-yl]
      propionic acid (2-Py-AMPA).
AB  - We have previously shown that whereas (RS)-2-amino-3-(3-hydroxy-5-phenylisoxazol
      4-yl)propionic acid (APPA) shows the characteristics of a partial agonist at (RS)
      2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, (S)
      APPA is a full AMPA receptor agonist and (R)-APPA a weak competitive AMPA
      receptor antagonist. This observation led us to introduce the new pharmacological
      concept, functional partial agonism. Recently we have shown that the 2-pyridyl
      analogue of APPA, (RS)-2-amino-3-[3-hydroxy-5-(2-pyridyl)isoxazol-4-yl]propionic
      acid (2-Py-AMPA), is a potent and apparently full AMPA receptor agonist, and this
      compound has now been resolved into (+)- and (-)-2-Py-AMPA (ee > or = 99.0%) by
      chiral HPLC using a Chirobiotic T column. The absolute stereochemistry of the
      enantiomers of APPA has previously been established by X-ray analysis, and on the
      basis of comparative studies of the circular dichroism spectra of the enantiomers
      of APPA and 2-Py-AMPA, (+)- and (-)-2-Py-AMPA were assigned the (S)- and (R)
      configuration, respectively. In a series of receptor binding studies, neither
      enantiomer of 2-Py-AMPA showed detectable affinity for kainic acid receptor sites
      or different sites at the N-methyl-D-aspartic acid (NMDA) receptor complex. (+)
      (S)-2-Py-AMPA was an effective inhibitor of [3H]AMPA binding (IC50 = 0.19 +/-
      0.06 microM) and a potent AMPA receptor agonist in the rat cortical wedge
      preparation (EC50 = 4.5 +/- 0.3 microM) comparable with AMPA (IC50 = 0.040 +/-
      0.01 microM; EC50 = 3.5 +/- 0.2 microM), but much more potent than (+)-(S)-APPA
      (IC50 = 5.5 +/- 2.2 microM; EC50 = 230 +/- 12 microM). Like (-)-(R)-APPA (IC50 >
      100 microM), (-)-(R)-2-Py-AMPA (IC50 > 100 microM) did not significantly affect
      [3H]AMPA binding, and both compounds were weak AMPA receptor antagonists (Ki =
      270 +/- 50 and 290 +/- 20 microM, respectively).

PMID- 9176993
TI  - Stereoselective inhibition of rat brain cyclooxygenase by dexketoprofen.
AB  - Although it has been assumed that the effects of nonsteroidal antiinflammatory
      drugs (NSAIDs) are mainly the result of their action on local synthesis of
      prostaglandins, there is growing evidence to suggest that they may also exert a
      central analgesic action. Some authors have suggested that inhibition of
      prostaglandin synthesis in the brain could contribute to the analgesic action.
      The effect of dexketoprofen trometamol (tromethamine salt of the enantiomer (+)-S
      ketoprofen) on prostaglandin synthesis was investigated in rat brain fragments
      and in cyclooxygenase preparations from rat brain microsomes. Effects of the (-)
      R-enantiomer and the racemic mixture were also evaluated. Significant levels of
      prostaglandin F2 alpha (PGF2 alpha) were synthesized in rat brain fragments after
      10 min of incubation at 37 degrees C. Dexketoprofen was found to be a potent
      inhibitor of this PGF2 alpha production in rat brain (IC50 = 6.2 nM), and it
      completely suppressed PGF2 alpha production at 1 microM concentration. In
      addition, inhibition of PGF2 alpha synthesis by dexketoprofen was highly
      stereoselective since the enantiomer (-)-R-ketoprofen was significantly less
      potent (IC50 = 294 nM); with this enantiomer, even at high concentrations such as
      1 microM, less than 60% inhibition was achieved. These results correlated with
      those obtained in the study of racemic ketoprofen and its enantiomers on
      cyclooxygenase activity of rat brain microsomes, where dexketoprofen also
      inhibited enzymatic activity stereoselectively. IC50 values obtained for
      dexketoprofen, (-)-R-ketoprofen, and rac-ketoprofen were 3.5 microM, 45.3 microM,
      and 5.8 microM, respectively. The above results could be related to the potent
      analgesic effect of dexketoprofen observed in vivo, which was also
      stereoselective. Taken together, these findings suggest that prostaglandin
      synthesis inhibition in rat brain by dexketoprofen could be associated, at least
      in part, with the analgesic effect of this NSAID.

PMID- 9176994
TI  - Allosteric modulation by single enantiomers of a C3-chiral 1,4-benzodiazepine of
      the gamma aminobutyric acid type A receptor channel expressed in Xenopus oocytes.
AB  - Xenopus laevis oocytes injected with Poly(A)(+)-RNA isolated from neuronal tissue
      express membrane proteins peculiar to the origin of mRNA. The translation of
      gamma aminobutyric acid type A (GABAA) receptors has been shown by dose/ response
      behavior of GABA and the reversible blockade of the GABA-induced current by
      picrotoxin. This current was analyzed quantitatively under two electrode voltage
      clamp conditions. This methodology has been applied for the first time to study
      the functional properties of the receptor as a function of the stereochemistry of
      the ligands. The (+)-S and (-)-R enantiomers of a water-soluble benzodiazepine
      derivative, 7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-1,4-benzodiazep in-2
      one (OXHEM), obtained by preparative high performance liquid chromatographic
      (HPLC) resolution on chiral stationary phase, act as agonists in the in vitro
      modulation of the chloride channel. The (+)-S-OXHEM enantiomer was the more
      active.

PMID- 9176995
TI  - Effect of sialic acid residues of human alpha 1-acid glycoprotein on
      stereoselectivity in basic drug-protein binding.
AB  - The function of sialic acid groups at the terminal of sugar chains of human alpha
      1-acid glycoprotein (AGP) was investigated with respect to chiral discrimination
      between optical isomers of basic drugs, using high-performance capillary
      electrophoresis/frontal analysis (HPCE/FA), a novel analytical method developed
      for the determination of unbound drug concentration with ultramicrosample volume
      (100-200 nl). Native human AGP and desialylated AGP were used as test proteins,
      and propranolol (PRO) and verapamil (VER) were used as model drugs. The unbound
      concentration of (S)-VER was 1.31 times higher than that of (R)-VER in native AGP
      solution. This selectivity was not affected by desialylation. Further, enzymatic
      elimination of galactose residues, which neighbored sialic acid groups, did not
      change the binding of either isomer of VER. On the other hand, the unbound
      concentration of (R)-PRO was 1.27 times higher than that of (S)-PRO in native AGP
      solution. Desialylation caused the unbound concentration of (S)-PRO to rise to
      the same level of (R)-PRO, resulting in loss of enantioselectivity. Thus, it
      follows that sialic acid groups of AGP, as a whole, are not responsible for
      chiral recognition between enantiomers of VER but are involved in
      enantioselectivity toward the isomers of PRO.

PMID- 9176996
TI  - Preliminary pharmacokinetic study of ibuprofen enantiomers after administration
      of a new oral formulation (ibuprofen arginine) to healthy male volunteers.
AB  - The pharmacokinetics of ibuprofen enantiomers were investigated in a crossover
      study in which seven healthy male volunteers received single oral doses of 800 mg
      racemic ibuprofen as a soluble granular formulation (sachet) containing L
      arginine (designated trade name: Spedifen), 400 mg (-)R-ibuprofen arginine or 400
      mg (+)S-ibuprofen arginine. Plasma levels of both enantiomers were monitored up
      to 480 minutes after drug intake using an enantioselective analytical method
      (HPLC with ultraviolet detection) with a quantitation limit of 0.25 mg/l.
      Substantial inter-subject variability in the evaluated pharmacokinetic parameters
      was observed in the present study. After (+)S-ibuprofen arginine, the following
      mean pharmacokinetic parameters +/-SD were calculated for (+)S-ibuprofen: tmax
      28.6 +/- 28.4 min; Cmax 36.2 +/- 7.7 mg/l; AUC 86.4 +/- 14.9 mg.h/l; t1/2 105.2
      +/- 20.4 min. After (-)R-ibuprofen arginine, the following mean pharmacokinetic
      parameters were calculated for (+)S-ibuprofen and (-)R-ibuprofen, respectively:
      tmax 90.0 +/- 17.3 and 50.5 +/- 20.5 min; Cmax 9.7 +/- 3.0 and 35.3 +/- 5.0 mg/l;
      AUC 47.0 +/- 17.2 and 104.7 +/- 27.7 mg.h/l; t1/2 148.1 +/- 63.6 and 97.7 +/-
      23.3 min. After racemic ibuprofen arginine, the following mean pharmacokinetic
      parameters were calculated for (+)S- and (-)R-ibuprofen, respectively: tmax 30.7
      +/- 29.1 and 22.9 +/- 29.8 min; Cmax 29.9 +/- 5.6 and 25.6 +/- 4.4 mg/l; AUC
      105.1 +/- 23.0 and 65.3 +/- 15.0 mg.h/l; t1/2 136.6 +/- 20.7 and 128.6 +/- 45.0
      min. Tmax values of S(+)- and (-)R-ibuprofen after a single dose of 400 mg of
      each enantiomer did not differ significantly from the corresponding parameters
      obtained after a single dose of 800 mg of racemic ibuprofen arginine, indicating
      that the absorption rate of (-)R- and (+)S-ibuprofen is not different when the
      two enantiomers are administered alone or as a racemic compound. An average of
      49.3 +/- 9.0% of a dose of the (-)R-ibuprofen arginine was bioinverted into its
      antipode during the study period (480 minutes post-dosing). The percent
      bioinversion during the first 30 minutes after (-)R-ibuprofen arginine intake
      averaged 8.1 +/- 3.9%. The mean AUC of (+)S-ibuprofen calculated after 800 mg
      racemic ibuprofen arginine (105.1 +/- 23.0 mg.h/l) was lower than the mean AUC
      value obtained by summing the AUCs of (+)S-ibuprofen after administration of 400
      mg (+)S-ibuprofen arginine and 400 mg (-)R-ibuprofen arginine (133.4 +/- 26.6
      mg.h/l). In conclusion, the administration of Spedifen resulted in very rapid
      absorption of the (+)S-isomer (eutomer) with tmax values much lower than those
      observed for this isomer when conventional oral solid formulations such as
      capsules or tablets of racemic ibuprofen are administered. This characteristic is
      particularly favourable in those conditions in which a very rapid analgesic
      effect is required.

PMID- 9176997
TI  - Pharmacokinetics of reboxetine enantiomers in the dog.
AB  - Reboxetine, (RS)-2-[(RS)-alpha-(2-ethoxyphenoxy)benzyl]morpholine
      methanesulphonate, is a racemic compound and consists of a mixture of the (R,R)-
      and (S,S)-enantiomers. The pharmacokinetics of reboxetine enantiomers were
      determined in a crossover study in three male beagle dogs. Each animal received
      the following oral treatments, separated by 1-week washout period: 10 mg/kg
      reboxetine, 5 mg/kg (R,R)- and 5 mg/kg (S,S)-. Plasma and urinary levels of the
      reboxetine enantiomers were monitored up to 48 h post-dosing using an
      enantiospecific HPLC method with fluorimetric detection (LOQ: 1.1 ng/ml in plasma
      and 5 ng/ml in urine for each enantiomer). After reboxetine administration mean
      tmax was about 1 h for both enantiomers. Cmax and AUC were about 1.5 times higher
      for the (R,R)- than for the (S,S)-enantiomer, mean values +/- SD being 704 +/-
      330 and 427 +/- 175 ng/ml for Cmax and 2,876 +/- 1,354 and 1,998 +/- 848 ng.h/ml
      for AUC, respectively. No differences between the (R,R)- and (S,S)-enantiomers
      were observed in t1/2 (3.9 h). Total recovery of the two enantiomers in urine was
      similar, the Ae (0-48 h) being 1.3 +/- 0.7 and 1.1 +/- 0.7% of the enantiomer
      dose for the (R,R)- and the (S,S)-enantiomers, respectively. No marked
      differences in the main plasma pharmacokinetic parameters were found for either
      enantiomer on administration of the single enantiomers or reboxetine. No chiral
      inversion was observed after administration of the separate enantiomers, as
      already observed in humans.

PMID- 9176998
TI  - Topical administration of racemic ibuprofen.
AB  - In vitro experiments to investigate possible stereoselective aspects of the
      topical administration of ibuprofen have been conducted. Incubation of ibuprofen
      with rat skin homogenates in the presence of coenzyme A, ATP, and magnesium
      provided no evidence for the formation of ibuprofenyl coenzyme A (the initial
      intermediate in the metabolic inversion of [R]- to [S]-ibuprofen). Similar
      incubation studies gave no indication of a change in the enantiomeric ratios of
      ibuprofen over the time course of the experiments. Percutaneous penetration
      studies of ibuprofen gel through porcine skin indicated that the ibuprofen
      enantiomer levels in the reservoir solutions were consistent with racemic
      ibuprofen having traversed the skin with no metabolic inversion. These results
      suggest that, in the models studied, skin metabolism does not result in the
      chiral inversion of (R)- to (S)-ibuprofen and that the topical administration of
      ibuprofen will result in the delivery of 50% "isomeric ballast."

PMID- 9176999
TI  - Studies on the in vitro inversion of flurbiprofen.
AB  - This paper reports in vitro studies on the metabolic inversion of flurbiprofen
      (FL), an arylpropionic acid antiinflammatory agent (2-APA). The inversion was
      studied with both rac-FL and R-FL, by incubation with rat hepatic microsomes, in
      the presence of either CoASH and ATP or NADPH. The two isomers of the drug were
      separated as their (+)-(R)-1-phenylethylamides by direct phase high-performance
      liquid chromatography on a silica gel column with an achiral mobile phase. The
      inversion was more pronounced in the presence of CoASH and ATP for both the
      racemate and the R-isomer, which supports the key role of CoA thioesters in the
      metabolic inversion of profens. The inversion observed in the presence of NADPH
      suggests that, when the incubation is run with hepatic microsomes, a CYP450
      mediated pathway is also active. In order to get more insight into the CYP450
      mediated inversion pathway, we studied the effect of irradiating microsomes with
      a low dose of He-Ne laser radiation (0.2 J). Such irradiation caused a
      significant increase in inversion at all times studied and normalized the
      anomalous value of inversion observed at 15 min in this pathway.

PMID- 9177000
TI  - The PRINTS database of protein fingerprints: a novel information resource for
      computational molecular biology.
AB  - PRINTS is a compendium of protein motif fingerprints derived from the OWL
      composite sequence database. Fingerprints are groups of motifs within sequence
      alignments whose conserved nature allows them to be used as signatures of family
      membership. Fingerprints inherently offer improved diagnostic reliability over
      single motif methods by virtue of the mutual context provided by motif neighbors.
      To date, 650 fingerprints have been constructed and stored in PRINTS, the size of
      which has doubled in the last 2 years. The current version, 14.0, encodes 3500
      motifs, covering a range of globular and membrane proteins, modular polypeptides,
      and so on. The database is now accessible via the UCL Bioinformatics Server on
      http:@ www.biochem.ucl.ac.uk/bsm/dbbrowser/. We describe here progress with the
      database, its compilation and interrogation software, and its Web interface.

PMID- 9177001
TI  - Automated resonance assignment of proteins using heteronuclear 3D NMR. 2. Side
      chain and sequence-specific assignment.
AB  - A sequential assignment protocol for proteins was developed using heteronuclear
      3D NMR. The protocol consists of an amino acid type recognition algorithm and a
      primary sequence mapping algorithm. The former measures the similarity between
      each detected spin pattern and 20 standard amino acid coupling patterns. Both
      chemical shift and topologically likeness are considered. The mapping algorithm
      uses the amino acid type information to direct detected polypeptides to proper
      position onto protein primary sequence. The assignment protocol can be applied to
      spin systems generated by many different approaches. We designed a few computer
      programs to derive a protein's backbone and side chain spin systems using
      heteronuclear 3D NMR. The results was then input to the sequential assignment
      protocol. All of the algorithms were tested on NMR data of a 90-residue N-domain
      of chicken skeletal troponin-C.

PMID- 9177002
TI  - The receptor-like neural network for modeling corticosteroid and testosterone
      binding globulins.
AB  - A neural-net method for simulation of corticosteroid and testosterone binding
      globulin (CBG, TBG)-ligand interactions is presented. Molecular modeling provides
      the geometry and partial atomic charges of 31 steroid molecules. The atomic
      coordinates within the molecule of the compound of the highest affinity are then
      used to train a self-organizing map (SOM) that forms a template for the
      comparison to other molecules. Comparison is done using a series of normalized
      patterns produced by the SOM. The template SOM, after overlaying on the set of
      random vectors, mimics the topology of the receptor site and is used to train
      unsupervisedly a neuron capable of recognizing the degree of similarity between
      the reference and tested patterns. A good correlation is observed for signals
      generated by the neuron plotted against the experimental CBG affinities. For TBG
      affinity modeling a modified procedure is designed which is capable of separating
      electrostatic and shape effects. The high predictive power of the model is
      achieved by keeping close analogy to the processes taking place at the real
      receptor sites.

PMID- 9177003
TI  - Similarity measures for rational set selection and analysis of combinatorial
      libraries: the Diverse Property-Derived (DPD) approach.
AB  - The generation of new chemical leads for biological targets is a very challenging
      task for researchers in the pharmaceutical industry. The design of representative
      screening sets and combinatorial libraries is central to achieving this
      objective. In this paper, we describe a novel molecular descriptor, the Diverse
      Property-Derived (DPD) code, that contains information about key molecular and
      physicochemical properties of a molecule. The utility of this descriptor is
      explored through its application for the selection of a maximally diverse
      representative screening set, through the selection of secondary screening sets
      to obtain more information concerning the structure-activity relationships (SAR)
      of a particular target receptor, and through the profiling of combinatorial
      libraries. The usefulness of physicochemical/molecular property descriptors, such
      as the DPD code, is discussed critically.

PMID- 9177004
TI  - Site accessibility and the pH dependence of the saturation capacity of a highly
      cross-linked matrix. Immobilized metal affinity chromatography of bovine serum
      albumin on chelating Superose.
AB  - Immobilized metal ion affinity chromatography has shown promise for isolating
      desired proteins from a mixture based on their affinity for chelated metal ions.
      Using frontal analysis, the pH dependence of the saturation capacity of chelating
      Superose matrix for bovine serum albumin (BSA) is examined over a broad pH range.
      A significant increase in the capacity was observed near the elution pH of BSA
      (pH 4.5) from a Cu-imminodiacetic acid column. The results of several experiments
      indicated that this apparently abnormal variation may reflect the low degree of
      accessibility of a large portion of copper sites inside chelating Superose. In a
      broader sense, these results suggest that during frontal analysis, the assumption
      of column saturation based on a plateau in the exit concentration that is almost
      at the same level as the input concentration could be misleading for highly cross
      linked matrices and relatively large sized proteins. That is, the relatively less
      accessible copper sites may become difficult to be reached due to high levels of
      protein adsorption in the more accessible regions and thus give the appearance of
      a plateau in the breakthrough curve prior to complete column saturation. This is
      likely to be the case at high pH where BSA demonstrates very high affinity for
      immobilized copper or at high input concentrations where the equilibrium coverage
      is expected to be high. The results demonstrate that the estimated saturation
      capacity could be significantly smaller than the actual capacity.

PMID- 9177005
TI  - Analysis of a monophosphoryl lipid A immunostimulant preparation from Salmonella
      minnesota R595 by high-performance liquid chromatography.
AB  - MPL immunostimulant, a 4'-monophosphoryl lipid A (MLA) preparation obtained from
      the lipopolysaccharide of Salmonella minnesota R595, is being developed for
      several clinical indications. MPL comprises a mixture of MLA congeners that
      contain 4, 5, and 6 fatty acids. In this paper, we report a new high-performance
      liquid chromatography (HPLC) method for analyzing the congener composition and
      purity of MPL. MPL is first derivatized with dinitrobenzyloxyamine (DNBA),
      resulting in incorporation of the dinitrobenzyl chromophore at the reducing end
      of all MLA congeners. DNBA-MPL is then analyzed by reversed-phase HPLC on a
      Waters NovaPak C18, 4 microns particle size, 300 mm x 3.9 mm column. Optimal
      separation of DNBA-MLA species is obtained using a linear gradient of 10% to 80%
      isopropanol-water (95:5, v/v), 5 mM tetrabutylammonium dihydrogenphosphate
      (TBAP), in acetonitrile-water (95:5, v/v), 5 mM.TBAP, over 45 min. A synthetic
      compound, corresponding to a hexaacyl MLA congener, is used for determination of
      the detector response factor, allowing the MLA content of MPL (i.e., purity) to
      be determined. Overall, this method provides better separation, higher
      sensitivity, and is faster and saler than previous methods used for the analysis
      of MPL.

PMID- 9177006
TI  - Analysis of bioactive peptides by liquid chromatography-high-resolution
      electrospray mass spectrometry.
AB  - LC-high-resolution electrospray ionization (ESI)-MS data for a number of
      bioactive peptides, including substance P and bradykinins were acquired over a
      wide mass range by scanning the magnetic sector and calibrating externally with
      polyethylene glycol standards. Multiply charged ions were observed and errors
      between observed and theoretical monoisotopic molecular masses were typically in
      the 5 to 30 ppm range for the peptides during LC-ESI-MS and ESI-MS operation with
      magnetic sector resolutions between 2500 and 6000 (10% valley definition). Under
      collisionally activated dissociation conditions bn- and yn-series sequence ions
      were generally observed, enabling amino acid sequencing and the differentiation
      of lysine from glutamine, two amino acids differing in residue mass by only
      0.0364 u. Mass accuracy was evaluated during an international round robin
      analytical exercise where the molecular masses of five unknown peptides were to
      be accurately determined. Isotopic clusters for charge states of up to +6 were
      fully resolved, facilitating the rapid and unambiguous assignment of charge
      states and calculation of monoisotopic molecular masses. Errors between
      theoretical and observed monoisotopic molecular masses were in the 2 to 18 ppm
      range for the five unknown peptides.

PMID- 9177007
TI  - High-performance liquid chromatography-electrospray ionisation-tandem mass
      spectrometry for the analysis of 1,2,3,4-tetrahydro-beta-carboline derivatives.
AB  - A rapid and sensitive method is described for the detection of 1,2,3,4-tetrahydro
      beta-carboline-3-carboxylic acid, 1-methyl-1,2,3,4- tetrahydro-beta-carboline-3
      carboxylic acid and 1-methyl-1,2,3,4-tetrahydro-beta-carboline by electrospray
      ionization tandem mass spectrometry coupled to liquid chromatography. In
      combination with selected reaction monitoring (SRM) detection limits of 3 ng ml-1
      (ca. 75 fmol on column) were established by the use of model solutions. Due to
      the excellent selectivity and sensitivity of SRM no sample preparation step was
      required prior to analysis of food samples. In addition, any artifactual
      formation of tetrahydro-beta-carbolines could be excluded. Application of the
      method revealed that all food samples analyzed contained both tetrahydro-beta
      carboline-carboxylic acids at ng ml-1 to microgram ml-1 concentrations, whereas 1
      methyl-1,2,3,4-tetrahydro- beta-carboline was identified in most samples as a
      minor constituent.

PMID- 9177008
TI  - Identification of phenolic acids and inositols in balms and tissues from an
      Egyptian mummy.
AB  - A number of samples taken from an Egyptian mummy (ca. 100 B.C.) from the Guimet
      Museum in Lyon have been analyzed by GC-MS. Derivatives of aromatic acids
      (hydroxyhydrocinnamic, vanillic, protocatechuic and gallic acids) and inositols
      (non-methylated and mono-O-methyl) have been found among the constituents of
      extracts prepared by methanolysis and trimethylsilylation. From the reported
      electron impact mass spectra, ion sets where proposed for a sensitive and
      selective profiling of these selected compounds by mass fragmentometry. The
      source of gallic acid and inositol was found to be a vegetable tannin, an
      ingredient which was not previously known to be used for mummification in ancient
      Egypt. The nature and abundance ratios of the detected inositols also appeared to
      be a promising criterion to further investigate the botanical source of the
      tannin employed.

PMID- 9177009
TI  - Study of haptoglobin-hemoglobin complexes by titration curves, capillary
      electrophoresis and capillary isoelectric focusing.
AB  - A novel method is described for monitoring complex formation between
      macromolecules, based on combined isoelectric focusing-electrophoresis in
      capillaries. The example studied is the binding of serum haptoglobin (Hp) to
      hemoglobin (Hb). A known amount of Hb is focused in a capillary in a pH 6-8 range
      (pI of Hb = 7.0) and thus kept temporarily "immobilized" in the electrophoretic
      chamber. Subsequently, increasing amounts of ligand (Hp) are loaded cathodically
      and allowed to sweep past the focused Hb zone. As the complex formed has a pI
      value well-outside the bounds of such a pH gradient (the 1:1 molar Hb-Hp complex
      has a pI of 5.5, the 1 to 1/2 molar Hp-Hb complex has a pI of 5.0) it escapes
      immobilization and moves past the detector window, where it is monitored and
      quantified. Since the detector is set at 416 nm, where only Hb absorbs, and since
      the molar extinction coefficient of Hb is well known, it is quite easy to
      calculate the molar amount of Hb bound to the complex. As an additional check,
      the amount of unreacted Hb can now be mobilized by disrupting the pH gradient and
      allowing this residual free Hb to also reach the detector and be quantified. The
      method is easy, fast, simple and fully automated and thus could represent a valid
      alternative to existing methods in clinical chemistry for quantifying the amount
      of Hp in human sera in pathological conditions, such as hemolytic anemias and
      transfusion reactions.

PMID- 9177010
TI  - Effect of endosulfan pesticide on the oxygen consumption rates of nauplii of
      different Spanish strains of Artemia.
AB  - This study was carried out to investigate the acute toxicity of endosulfan, an
      organochlorine pesticide, and the effect of a sub-lethal concentration of this
      compound on the rate of oxygen consumption (MO2) of three different Spanish
      strains of Artemia neuplii. The 24 h LC50 values showed that the nauplii of the
      parthenogenetic diploid strain were more resistant, whereas those of the
      parthenogenetic tetraploid and bisexual strains were more sensitive to endosulfan
      and did not show differences between them. The results suggest that the use of
      different Artemia strains, with their differing degree of sensitivity to the same
      toxicant, may be a valuable tool in aquatic ecotoxicological research. Exposure
      to sub-lethal concentrations (1/5-24hLC50) of endosulfan had no significant
      effect on the oxygen consumption rates (MO2) of each strain of the nauplii.
      Nevertheless, a reduction in the ability of the nauplii to maintain respiratory
      independence during hypoxia, after 24 h exposure to such dose, was observed.

PMID- 9177011
TI  - Effects of maternal exposure to chlorinated diphenyl ethers on thyroid hormone
      concentrations in maternal and juvenile rats.
AB  - Polychlorinated diphenyl ethers (PCDEs) are industrial byproducts and widespread
      environmental contaminants. Their structural similarity to PCBs suggests that
      they may exhibit subtle effects on both adult and juvenile mammals. We examined
      the effects of 3 PCDEs (2,2',4,5,6'-pentachlorodiphenyl ether, 2',3,4,6'
      tetrachlorodiphenyl ether, and 2,2',4,4',5,5'-hexachlorodiphenyl ether) on
      maternal rat thyroid levels shortly after exposure, and on the thyroid levels of
      16 day old juvenile rats that had been prenatally exposed. Both 2,2',4,5, 6'
      pentachlorodiphenyl ether and 2',3,4,6'-tetrachlorodiphenyl ether depressed
      thyroxine (T4) levels in the maternal females as well as in both sexes of
      juvenile rats. 2,2',4,4',5,5'-hexachlorodiphenyl ether did not alter T4 levels in
      the pregnant females, but depressed juvenile T4 levels. None of the congeners
      studied significantly altered T3 levels. Effects on thyroid hormones did not
      correlate with the congeners' induction of cytochrome P450.

PMID- 9177012
TI  - Mercuric chloride-induced reactive oxygen species and its effect on antioxidant
      enzymes in different regions of rat brain.
AB  - The present study was undertaken to determine if in vitro exposure to mercuric
      chloride produces reactive oxygen species (ROS) in the synaptosomes prepared from
      various regions of rat brain. The effects of in vivo exposure to mercury on
      antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) activities in different regions of rat brain were also investigated. Adult
      male Sprague-Dawley (CD) rats were dosed with 0, 1, 2.0 or 4.0 mg HgCl2/kg body
      weight, for 7 days. One week after the last dose, animals were sacrificed by
      decapitation, their brains were removed and dissected and frozen in dry ice prior
      to measuring the activities of these enzymes. The results demonstrated that in
      vitro exposure to mercury produced a concentration-dependent increase of ROS in
      different regions of the rat brain. In vivo exposure to mercury produced a
      significant decrease of total SOD, Cu, Zn-SOD and Mn-SOD activities in the
      cerebellum of rats treated with different doses of mercury. SOD activity did not
      vary significantly in cerebral cortex and brain stem. GPx activity declined in a
      dose-dependent manner in the cerebellum with a significant reduction in animals
      receiving the 4 mg HgCl2/kg body weight. The activity of GPx increased in the
      brain stem while unchanged in the cerebral cortex. The results demonstrate that
      inorganic mercury decreased SOD activity significantly in the cerebellum while
      GPx activity was affected in both cerebellum and brain stem. Therefore, it can be
      concluded that oxidative stress may contribute to the development of
      neurodegenerative disorders caused by mercury intoxication.

PMID- 9177013
TI  - [Ovarian activity of Drosophila melanogaster Meigen (Diptera), during a chronic
      intoxication with four fungicides: anatomical and cytological study].
AB  - Two types of reactions were observed on the alteration of Drosophila
      vitellogenesis by the four fungicides used in this study. Dithane M45 resulted in
      stimulation associated with egg retention. However, the other three fungicides
      (Benlate, Bouillie bordelaise and Euparene) resulted in inhibition to a varying
      degree. Although the inhibition was comparatively limited due to Benlate it
      induced an egg retention. The inhibition was very high due to Bouillie bordelaise
      and Euparene. With Bouillie bordelaise an egg retention occured together with the
      reduction of vitellogenesis and caused an increase in the rate of the follicle
      resorption. The latter depended on the duration of treatment. With Euparene, no
      egg retention was observed and the toxicity was only noticed on vitellogenesis.

PMID- 9177014
TI  - Effect of the appetite stimulant cyproheptadine on deoxynivalenol-induced
      reductions in feed consumption and weight gain in the mouse.
AB  - Deoxynivalenol (DON, vomitoxin), a Fusarium mycotoxin, is suspected of inducing
      its anorectic/feed refusal activity through a serotoninergic (5HT) mechanism,
      possible via 5HT2-receptors. In this study the efficiency of cyproheptadine
      (CYP), a serotonin antagonist and known appetite stimulant, to attenuate the
      adverse effect of DON was investigated in mice. CYP was administered in the feed
      for two days before animals began receiving the DON, which was also added to the
      feed. Both agents were administered concurrently thereafter for a 12-day period.
      Dosing levels included various combinations of the two compounds, ranging from 0
      16 ppm DON and 0-20 ppm CYP.

PMID- 9177015
TI  - Influence of the dielectric property on microwave oven heating patterns:
      application to food materials.
AB  - Patterns of power absorption in a microwave oven for a range of dielectric
      properties of relevance to food processing were investigated. The governing
      Maxwell's equations with boundary conditions and a TE10 excitation were solved
      using a finite element method. Food properties were varied from values at their
      frozen state to values at high temperatures, as would be typical in a thawing
      process. For low-loss materials such as frozen foods, the high quality factor
      makes the heating significantly higher only when the size and shape of the load
      permit a dielectric cavity resonance in the load. Otherwise, the heating pattern
      will follow the modal electric field pattern of the oven. For moderate loss
      materials, the patterns will come from the modes of the dielectric cavity. The
      bandwidths of these modes are larger than the low-loss situation and their
      overlap results in a heating pattern that is somewhat more uniform. For high-loss
      materials, the concept of modes is no longer useful as the very large number of
      modes strongly overlap. The rapidly decaying field and power loss in the high
      loss material can probably be characterized as an exponential decay.

PMID- 9177016
TI  - Further study of microwave power absorption in a multilayered cylindrical model
      of man.
AB  - The paper describes microwave power absorption in a typical human being, modeled
      as a multilayered dielectric cylinder. Average specific absorption rate (SAR) was
      calculated for E- and H- polarized incident wave for different conditions of the
      object. Comparison with an existing method is treated, and correction of an
      erroneous result therein is reported.

PMID- 9177017
TI  - Assessment of microwave sterilization of foods using intrinsic chemical markers.
AB  - The uniformity of microwave processing was investigated by measuring the
      formation of intrinsic chemical markers in disc-shaped and cylindrically-shaped
      whey protein gel model systems. These markers are formed as a result of thermally
      induced reactions of sugar and protein precursors. They were measured in samples
      placed in a pressurizable Teflon vessel and microwave heated to different peak
      temperatures using different power levels. Heating uniformity was mapped by
      sectioning the sample and analyzing for markers. The destruction of B.
      stearothermophilus spores in alginate beads was correlated with marker formation.
      The results show that the markers can be used to assess sterility and spatial
      time-temperature distributions in solid food samples.

PMID- 9177018
TI  - Individual and collective processes in the construction of the self: self
      enhancement in the United States and self-criticism in Japan.
AB  - A collective constructionist theory of the self proposes that many psychological
      processes, including enhancement of the self (pervasive in the United States) and
      criticism and subsequent improvement of the self (widespread in Japan), result
      from and support the very ways in which social acts and situations are
      collectively defined and subjectively experienced in the respective cultural
      contexts. In support of the theory, 2 studies showed, first, that American
      situations are relatively conducive to self-enhancement and American people are
      relatively likely to engage in self-enhancement and, second, that Japanese
      situations are relatively conducive to self-criticism and Japanese people are
      relatively likely to engage in self-criticism. Implications are discussed for the
      collective construction of psychological processes implicated in the self and,
      more generally, for the mutual constitution of culture and the self.

PMID- 9177019
TI  - The cultural construction of self-enhancement: an examination of group-serving
      biases.
AB  - Self-serving biases, found routinely in Western samples, have not been observed
      in Asian samples. Yet given the orientation toward individualism and collectivism
      in these 2 cultures, respectively, it is imperative to examine whether parallel
      differences emerge when the target of evaluation is the group. It may be that
      Asians show a group-serving bias parallel to the Western self-serving bias. In 2
      studies, group-serving biases were compared across European Canadian, Asian
      Canadian, and Japanese students. Study 1 revealed that Japanese students
      evaluated a family member less positively than did both groups of Canadian
      students. Study 2 replicated this pattern with students' evaluations of their
      universities. The data suggest that cultural differences in enhancement biases
      are robust, generalizing to individuals' evaluations of their groups.

PMID- 9177020
TI  - In a very different voice: unmasking moral hypocrisy.
AB  - Across 3 small studies, 80 female undergraduates were confronted with the dilemma
      of deciding whom-themselves or another research participant-to assign to a
      positive consequences task, leaving the other to do a dull, boring task. In Study
      1, where morality was not mentioned, 16 of 20 assigned themselves to the positive
      consequences task, even though in retrospect only 1 said this was moral. In
      Studies 2 and 3, a moral strategy was suggested: either flipping a coin or
      accepting task assignment by the experimenter. In Study 2, 10 of 20 participants
      flipped a coin, but of these, 9 assigned themselves the positive consequences
      task. In Study 3, participants were significantly more likely to accept the
      experimenter's assignment when it gave them the positive consequences task.
      Overall, results suggested motivation to appear moral yet still benefit oneself.
      Such motivation is called moral hypocrisy.

PMID- 9177021
TI  - Mixed messages: implications of social conflict and social support within close
      relationships for adjustment to a stressful life event.
AB  - The authors examined the impact of women's perceptions of negative (conflict) and
      positive (support) exchanges with their mothers, partners, and friends before
      having an abortion on negative (distress) and positive (well-being) indexes of
      adjustment after the abortion. Preabortion conflict and support from the partner
      predicted postabortion adjustment in the same affective domain: Conflict uniquely
      predicted distress, whereas support uniquely predicted well-being. Within-source
      interactions were observed between support and conflict from mothers and friends.
      Women who perceived high support from their mothers or friends were more
      distressed if they also perceived them as sources of high conflict than if they
      perceived them as sources of low conflict. Among women who perceived their
      mothers or friends as nonsupportive, no relationship was observed between
      conflict and distress. Cross-source buffering was not observed.

PMID- 9177022
TI  - Willingness to sacrifice in close relationships.
AB  - The authors advance an interdependence analysis of willingness to sacrifice.
      Support for model predictions was revealed in 6 studies (3 cross-sectional survey
      studies, 1 simulation experiment, 2 longitudinal studies) that used a novel self
      report measure and a behavioral measure of willingness to sacrifice. Willingness
      to sacrifice was associated with strong commitment, high satisfaction, poor
      alternatives, and high investments; feelings of commitment largely mediated the
      associations of these variables with willingness to sacrifice. Moreover,
      willingness to sacrifice was associated with superior couple functioning,
      operationalized in terms of level of dyadic adjustment and probability of couple
      persistence. In predicting adjustment, willingness to sacrifice accounted for
      significant variance beyond commitment, partially mediating the link between
      commitment and adjustment; such mediation was not significant for persistence.

PMID- 9177023
TI  - Approach and avoidance motivation in psychopathic criminal offenders during
      passive avoidance.
AB  - The authors evaluated competing theories that attribute psychopathic individuals'
      poor passive avoidance to a strong activating system, a weak inhibitory system,
      or poor modulation of behavioral activation when inhibitory cues appear. In Study
      1, the continuous motor task involved a reward phase to elicit the activating
      system followed by a passive avoidance phase. Study 2 tested the generality of
      the theories by using an active avoidance phase to elicit the activating system.
      Heart rate and response speed results from Study 1 best supported the strong
      activating system and poor response modulation models in low-anxiety psychopathic
      offenders. Study 2 results did not clearly support any of the models. Further
      research is needed to determine if excessive activation by reward and poor
      response modulation are associated with passive avoidance deficits and other
      characteristics of low-anxiety psychopathic offenders.

PMID- 9177024
TI  - The ability to detect deceit generalizes across different types of high-stake
      lies.
AB  - The authors investigated whether accuracy in identifying deception from demeanor
      in high-stake lies is specific to those lies or generalizes to other high-stake
      lies. In Experiment 1, 48 observers judged whether 2 different groups of men were
      telling lies about a mock theft (crime scenario) or about their opinion (opinion
      scenario). The authors found that observers' accuracy in judging deception in the
      crime scenario was positively correlated with their accuracy in judging deception
      in the opinion scenario. Experiment 2 replicated the results of Experiment 1, as
      well as P. Ekman and M. O'Sullivan's (1991) finding of a positive correlation
      between the ability to detect deceit and the ability to identify micromomentary
      facial expressions of emotion. These results show that the ability to detect high
      stake lies generalizes across high-stake situations and is most likely due to the
      presence of emotional clues that betray deception in high-stake lies.

PMID- 9177025
TI  - Links between race/ethnicity and cultural values as mediated by racial/ethnic
      identity and moderated by gender.
AB  - Two studies examined whether individualism (orientation toward one's own
      welfare), collectivism (orientation toward the welfare of one's larger
      community), and familism (orientation toward the welfare of one's immediate and
      extended family) are distinct cultural values predicted by race/ ethnicity. The 3
      constructs proved to be separate dimensions, although collectivism and familism
      were positively correlated. In Study 1, persons of color scored higher on
      collectivism and familism than did Anglos. No differences emerged for
      individualism. Also, persons of color scored higher than Anglos on racial/ethnic
      identity, which in turn was a positive predictor of all 3 cultural values. In
      Study 2, we replicated the group differences on collectivism and familism for men
      but not for women.

PMID- 9177026
TI  - Changes in photosystem stoichiometry in response to environmental conditions for
      cell growth observed with the cyanophyte Synechocystis PCC 6714.
AB  - Changes in photosystem stoichiometry in response to shift of environments for
      cell growth other than light regime were studied with the cyanophyte
      Synechocystis PCC 6714 in relation to the change induced by light-quality shift.
      Following two environment-shifts were examined: the shift of molecular form of
      inorganic carbon source for photosynthesis from CO2 to HCO3- (CO2 stress) and the
      increase in salinity of the medium with NaCl (0.5 M) (Na+ stress). Both CO2 and
      Na+ stresses induced the increase in PSI abundance resulting in a higher PSI/PSII
      stoichiometry. CO2 stress was found to elevate simultaneously Cyt c oxidase
      activity (Vmax). The feature was the same as that caused by light-quality shift
      from preferential excitation of PSI to PSII (light stress) though the enhancement
      by either stress was smaller than that by light stress. Under our experimental
      conditions, PSI/PSII stoichiometry appeared to increase at a fairly constant rate
      to the basal level even when the basal level had been differently determined by
      the light-quality. Enhancing rates for PSI/PSII stoichiometry and for Cyt c
      oxidase activity were also similar to each other. Since the two stresses affect
      the thylakoid electron transport similarly to the shift of light-quality, we
      interpreted our results as follows: three environmental stresses, CO2, Na+, and
      light stresses, cause changes in electron turnover capacity of PSI and Cyt c
      oxidase under a similar, probably a common, mechanism for monitoring redox state
      of thylakoid electron transport system.

PMID- 9177027
TI  - Molecular cloning, expression and subcellular localization of a BiP homolog from
      rice endosperm tissue.
AB  - The ER luminal binding protein, BiP, has been linked to prolamine protein body
      formation in rice. To obtain further information on the possible role of this
      chaperone in protein body formation we have cloned and sequenced a BiP cDNA
      homolog from rice endosperm. The rice sequence is very similar to the maize BiP
      exhibiting 92% nucleotide identity and 96% deduced amino acid sequence identity
      in the coding region. Substantial amino acid sequence homology exists between
      rice BiP and BiP homologs from several other plant and animal species including
      long stretches of conservation through the amino-terminal ATPase domain.
      Considerable variation, however, is observed within the putative carboxy-terminal
      peptide-binding domain between the plant and nonplant BiP sequences. A single
      hand of approximately 2.4 kb was visible when RNA gel blots of total RNA purified
      from seed tissue were probed with radiolabeled rice BiP cDNA. This band increased
      in intensity during seed development up to 10 days after flowering, and then
      decreased gradually until seed maturity. Protein gel blots indicated that BiP
      polypeptide accumulation parallels that of the prolamine polypeptides throughout
      seed development. Immunocytochemical analysis demonstrated that BiP is localized
      in a non-stochastic fashion in the endoplasmic reticulum membrane complex of
      developing endosperm cells. It is abundant on the periphery of the protein
      inclusion body but not in the central portion of the protein body or in the
      cisternal ER membranes connecting the protein bodies. These data support a model
      which proposes that BiP associates with the newly synthesized prolamine
      polypeptide to facilitate its folding and assembly into a protein inclusion body,
      and is then recycled.

PMID- 9177028
TI  - Extracellular components implicated in the stationary organization of the actin
      cytoskeleton in mesophyll cells of Vallisneria.
AB  - In mesophyll cells of Vallisneria gigantea Graebner, an aquatic angiosperm, the
      association of the plasma membrane with the cell wall at the end wall has been
      reported to be indispensable for the mechanism that maintains the stationary
      organization of the bundles of microfilaments (MFs) [Masuda et al. (1991)
      Protoplasma 162: 151]. To identify putative extracellular components that might
      play a crucial role in this mechanism, we examined the effects of two exogenously
      applied synthetic hexapeptides, GRGDSP and ARYDEI, which include an RGD and an
      RYD motif, respectively. The RGD motif is known as a recognition site in
      molecules required for adhesion to the substratum at sites of focal contacts.
      Within 24 h, both peptides (at concentrations of 1-15 mM) induced extremely
      abnormal patterns of cytoplasmic streaming, as well as the striking disruption of
      the arrangement of bundles of MFs. GRGESP and ARYEEI peptides, used as controls,
      had no detectable effects. Immunofluorescence microscopy revealed that polyclonal
      antibodies against the ARYDEI peptide bound to the cell walls of mesophyll cells
      while a preimmune serum did not. Western blotting analysis demonstrated that the
      antibodies recognized polypeptides of 54 kDa and 27 kDa in an extract of total
      proteins from the leaves of Vallisneria. The results suggest that some
      extracellular proteins(s), with a conserved RGD or RYD motif in its amino acid
      sequence, might be involved in the maintenance of the stationary organization of
      the bundles of MFs.

PMID- 9177029
TI  - Inactivation and degradation of CuZn-SOD by active oxygen species in wheat
      chloroplasts exposed to photooxidative stress.
AB  - Changes in CuZn-SOD activity and content in isolated wheat chloroplasts under the
      light, and the involvement of protease(s) and/or active oxygen species in this
      process were studied. Both SOD activity and content decayed with exposure time to
      photooxidative stress. Ascorbate, a H2O2 scavenger, prevented photooxidation
      associated inactivation of SOD, while benzoate, a .OH scavenger, prevented SOD
      degradation. Wheat chloroplasts incubated in the dark did not hydrolyze exogenous
      or endogenous SOD, either H2O2-pretreated or not. Protease inhibitors did not
      prevent SOD degradation under photooxidative treatment, suggesting that plastid
      protease(s) did not participate in this process. Purified chloroplast CuZn-SOD
      was exposed to H2O2 and O2- or .OH-generating systems. O2- had no effect on
      either SOD activity or stability (estimated by native PAGE). H2O2 up to 700
      microM inhibited SOD in a dose-dependent manner and induced charge/mass changes
      as seen by native PAGE. .OH also reduced SOD activity by inducing its
      fragmentation. High levels of active oxygen, as can be generated under strong
      stress conditions, could directly inactivate and degrade chloroplastic SOD.

PMID- 9177030
TI  - Identification of chitinase and osmotin-like protein as actin-binding proteins in
      suspension-cultured potato cells.
AB  - Cytoplasmic aggregation is an early resistance-associated event that is observed
      in potato tissues either after penetration of an incompatible race of
      Phytophthora infestans, the potato late blight fungus, or after treatment with
      hyphal wall components (HWC) prepared from P. infestans. In potato cells in
      suspension culture, the number of cells with cytoplasmic aggregation increased
      upon treatment with HWC, but such an increase was suppressed by treatment with
      cytochalasin D prior to treatment with HWC. This result suggested that
      cytoplasmic aggregation in cultured potato cells might be connected with the
      association of actin filaments. To identify the molecular basis of cytoplasmic
      aggregation, we purified actin and actin-related proteins by affinity
      chromatography on a column of immobilized DNase I from cultured potato cells and
      isolated proteins of 43 kDa, 32 kDa and 22 kDa. Analysis of the amino-terminal
      amino acid sequences indicated that the 43 kDa, 32 kDa and 22 kDa proteins were
      potato actin, basic chitinase and osmotin-like protein, respectively. This
      conclusion was supported by the results of Western blotting analysis of the 43
      kDa and 32 kDa proteins with antibodies against actin and basic chitinase.
      Binding analysis with actin coupled to actin-specific antibodies and biotinylated
      actin suggested that the 32 kDa and 22 kDa proteins had actin-binding activity.
      In addition, examination of biomolecular interactions using an optical biosensor
      confirmed the binding of chitinase to actin. These results imply the possibility
      that basic chitinase and osmotin-like protein might be involved in cytoplasmic
      aggregation, hereby participating. In the potato cell's defense against attack by
      pathogen.

PMID- 9177031
TI  - Hydroxypyruvate reductase with a carboxy-terminal targeting signal to microbodies
      is expressed in Arabidopsis.
AB  - Five Arabidopsis EST cDNA clones of hydroxypyruvate reductase (HPR), a
      photorespiratory enzyme in leaf peroxisomes, were sequenced. Deduced amino acid
      sequences revealed that HPR in Arabidopsis contained the carboxy-terminal
      targeting signal to microbodies. Nucleotide sequence analysis showed that the
      cDNA with the longest insert contained an open reading frame of 1,158 bp which
      encoded a polypeptide with 386 amino acids with a calculated molecular mass of
      42,251 Da. A Southern blot analysis suggested that the Arabidopsis HPR gene, like
      that of the pumpkin HPR gene, exists as a single copy. Two kinds of pumpkin HPR
      mRNA might be produced from a single gene by alternative splicing, but the
      structure of the genomic DNA indicated that the Arabidopsis HPR gene did not
      undergo alternative splicing. We detected a polypeptide with a molecular mass of
      42 kDa in green leaves of Arabidopsis using an HPR-specific antibody.
      Immunoelectron microscopy revealed that Arabidopsis HPR protein was exclusively
      localized in leaf peroxisomes in green leaves. These results indicate that HPR is
      expressed in a form with a carboxy-terminal targeting signal to microbodies and
      is localized in microbodies in Arabidopsis, suggesting that the differences in
      the gene structure and the regulation of gene expression of HPR are probably due
      to species-specific differences in plants.

PMID- 9177032
TI  - Differential expression of CuZn- and Fe-superoxide dismutase genes of tobacco
      during development, oxidative stress, and hormonal treatments.
AB  - Chloroplasts of Nicotiana tabacum have two superoxide dismutases: a Fe- and a
      CuZn-containing enzyme, encoded by the nuclear genes sodB and sodCp,
      respectively. As a first step in studying the physiological function of these two
      enzymes, we compared the expression of sodB and sodCp in different plant organs,
      in response to hormonal treatments, and upon treatment with paraquat and
      Norflurazon. The sodCp transcript and active enzyme were detected only in young
      leaves of mature plants. The sodB transcript was more abundant in young compared
      to old leaves, but the enzymatic activity was higher in mature and senescent
      leaves. sodCp and sodB exhibited a different expression pattern upon treatment
      with abscisic acid, indole-3-acetic acid, kinetin, gibberellin, and 1
      aminocyclopropane-1-carboxylate. Paraquat treatment caused a decrease in
      abundance of both transcripts, although the dose dependency of this decrease
      differed. Norflurazon-induced photooxidation resulted in a 10-fold increase of
      sodCp mRNA whereas the sodB transcript level was 25% higher than the control.
      These differences in expression might explain why both plastid-located superoxide
      dismutase enzymes are needed, particularly under stress conditions.

PMID- 9177033
TI  - The large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase is
      fragmented into 37-kDa and 16-kDa polypeptides by active oxygen in the lysates of
      chloroplasts from primary leaves of wheat.
AB  - Lysates of chloroplasts isolated from wheat (Triticum aestivum L. cv. Aoba)
      leaves were incubated on ice (pH 5.7) for 0 to 60 min in light (15 mumol quanta m
      2 s-1), and degradation of the large subunit (LSU) of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco: EC 4.1.1.39) was analyzed by applying
      immunoblotting with site-specific antibodies against the N-terminal, internal,
      and C-terminal amino acid sequences of the LSU of wheat Rubisco. The most
      dominant product of the breakdown of the LSU and that which was first to appear
      was an apparent molecular mass of 37-kDa fragment containing the N-terminal
      region of the LSU. A 16-kDa fragment containing the C-terminal region of the LSU
      was concomitantly seen. This fragmentation of the LSU was inhibited in the
      presence of EDTA or 1,10-phenanthroline. The addition of active oxygen
      scavengers, catalase (for H2O2) and n-propyl gallate (for hydroxyl radical) to
      the lysates also inhibited the fragmentation. When the purified Rubisco from
      wheat leaves was exposed to a hydroxyl radical-generating system comprising H2O2,
      FeSO4 and ascorbic acid, the LSU was degraded in the same manner as observed in
      the chloroplast lysates. The results suggest that the large subunit of Rubisco
      was directly degraded to the 37-kDa fragment containing the N-terminal region and
      the 16-kDa fragment containing the C-terminal region of the LSU by active oxygen,
      probably the hydroxyl radical, generated in the lysates of chloroplasts.

PMID- 9177034
TI  - Immunolocalization of the lectins P2 and P4 from Dioclea lehmanni seeds.
AB  - Intracellular localization of the lectins P2 and P4 from Dioclea lehmanni in
      developing cotyledons and in mature embryo axis were analyzed by the immunogold
      method. In parenchyma cells of the mature cotyledons both lectins were found in
      the protein bodies, whereas in immature cotyledons and in mature embryo axis
      these lectins were exclusively localized in the vacuoles.

PMID- 9177035
TI  - Molecular cloning and characterization of a MADS-box cDNA clone of the Fuji
      apple.
AB  - A cDNA clone, MdMADS1, containing MADS domain was isolated from the Fuji apple.
      The gene was expressed in all floral organs and young fruits but not in leaves.
      The expression was higher at the early stages of flower and fruit developments,
      suggesting that MdMADS1 plays a major role in the initiation of reproductive
      organ developments.

PMID- 9177036
TI  - Plastid distribution in columella cells of a starchless Arabidopsis mutant grown
      in microgravity.
AB  - Wild-type and starchless Arabidopsis thaliana mutant seedlings (TC7) were grown
      and fixed in the microgravity environment of a U.S. Space Shuttle spaceflight.
      Computer image analysis of longitudinal sections from columella cells suggest a
      different plastid positioning mechanism for mutant and wild-type in the absence
      of gravity.

PMID- 9177037
TI  - MROS1, a male stamen-specific gene in the dioecious campion Silene latifolia is
      expressed in mature pollen.
AB  - The MROS1 gene, one of the genes that are expressed specifically in male
      reproductive organs of a dioecious campion Silene latifolia, was predicted to
      encode only 36 amino acids but have an intron. In situ hybridization revealed
      that MROS1 mRNA was localized in mature pollen grains.

PMID- 9177038
TI  - Resonance Raman spectroscopy of 2H-labelled spheroidenes in petroleum ether and
      in the Rhodobacter sphaeroides reaction centre.
AB  - As a step towards the structural analysis of the carotenoid spheroidene in the
      Rhodobacter sphaeroides reaction centre, we present the resonance Raman spectra
      of 14-2H, 15-2H, 15'-2H, 14'-2H, 14,15'-2H2 and 15-15'-2H2 spheroidenes in
      petroleum ether and, except for 14,15'-2H2 spheroidene, in the Rb. sphaeroides
      R26 reaction center (RC). Analysis of the spectral changes upon isotopic
      substitution allows a qualitative assignment of most of the vibrational bands to
      be made. For the all-trans spheroidenes in solution the resonance enhancement of
      the Raman bands is determined by the participation of carbon carbon stretching
      modes in the centre of the conjugated chain, the C9 to C15' region. For the RC
      bound 15,15'-cis spheroidenes, enhancement is determined by the participation of
      carbon-carbon stretching modes in the centre of the molecule, the C13 to C13'
      region. Comparison of the spectra in solution and in the RC reveals evidence for
      an out-of-plane distortion of the RC-bound spheroidene in the central C14 to C14'
      region of the carotenoid. The characteristic 1240 cm-1 band in the spectrum of
      the RC-bound spheroidene has been assigned to a normal mode that contains the
      coupled C12-C13 and C13'-C12' stretch vibrations.

PMID- 9177039
TI  - A 4-term energy level scheme for the high-spin ferrous hemoproteins: evidence for
      the 5E eta, and 5B2 terms as the ground multiplets in hemoproteins with a
      histidine and a cysteine protein-derived heme ligand, respectively.
AB  - We have carried out analysis of the electronic level scheme of the high-spin
      ferrous hemoproteins by simultaneous fit of the adjustable parameters of a 4-term
      theoretical model to low-temperature magnetic circular dichroism (MCD), room
      temperature absorption spectra and available magnetic susceptibility and or
      Mossbauer data of myoglobin, horseradish peroxidase and cytochrome P450. The high
      reliability of the ligand field parameter values obtained for deoxymyoglobin is
      confirmed by good agreement between the predicted and observed magnetic field
      dependences of MCD and magnetization not used in the fit procedure. In addition,
      an energy gap between the ground and first excited singlets, estimated to be 4.2
      cm-1, agrees well with the value of approximately 4 cm-1 derived from the far
      infrared magnetic resonance. Our computer and explicit theoretical analyses give
      strong evidence that large distinctions in the shape, intensity and temperature
      behaviour of the MCD of Mb and HRP from those of cytochrome P450 can be described
      only if the ground manifold in these proteins is 5E eta and 5B2, respectively.
      The changes in relative energies of the one-electron 3d-orbitals on substitution
      of an imidazole of histidine for a sulphur anion of cysteine as a protein-derived
      heme iron ligand are rationalized by the lower ionization potential of the
      negatively charged sulphur ligand and the higher pi-orbital overlap of its lone
      pair orbitals with the iron d pi-orbitals compared to the imidazole ligand.

PMID- 9177040
TI  - Single site electronic spectra of free base porphin in an n-octane crystal at 5
      K.
AB  - The single site fluorescence and excitation spectra of free base porphin in an n
      octane crystal at 5 K are reported. The vibrational frequencies of the ground and
      excited states (Qx, Qy, and B bands) have been determined from the spectra. The
      Qx region is very similar to the previously reported results from supersonic jet
      expansion. However, the Qy region is quite different in the jet and mixed
      crystal: the crystal spectrum exhibits extensive vibronic coupling. The Soret
      band shows little vibronic structure.

PMID- 9177041
TI  - Sugar oxidoreductases and veratryl alcohol oxidase as related to lignin
      degradation.
AB  - Properties of cellobiose:quinone oxidoreductase (CBQ), cellobiose dehydrogenase
      (CDH), glyoxal oxidase (GLOX), glucose oxidases and veratryl alcohol oxidase
      (VAO) are reviewed. There is strong evidence that CDH reduces quinones, phenoxy
      and cation radicals. Glucose oxidases (glucose 1-oxidase and pyranose 2-oxidase)
      and VAO have been less investigated but evidence for reduction of the above
      compounds is accumulating. Pyranose oxidase, glyoxal oxidase and VAO are very
      important for hydrogen peroxide production by white-rot fungi. CDH is only
      produced on cellulose or on wood, whereas pyranose oxidase and VAO are produced
      both on wood and on rich glucose media suggesting that the lignin degrading white
      rot fungi may use different quinone and radical reducing enzymes to regulate
      lignin polymerization/depolymerization depending on the substrate and cultivation
      conditions. Intracellular quinone reductases are also produced. Whether brown-rot
      fungi in general produce CBQ/CDH or VAO is not clear. The Fe(III) reducing
      ability of both CDH and certain phenolate compounds agree with the rapid
      depolymerization of cellulose by brown-rot fungi. The interaction of Fe(III)
      reduction with the hydrogen peroxide producing system in white-rot and brown-rot
      fungi requires more investigation.

PMID- 9177046
TI  - Recent advances on the molecular genetics of ligninolytic fungi.
AB  - This review highlights significant recent advances in the molecular genetics of
      white-rot fungi and identifies areas where information remains sketchy. The
      development of critical experimental tools such as genetic mapping techniques is
      described. A major portion of the text focuses on the structure, genomic
      organization and transcriptional regulation of the genes encoding peroxidases,
      laccases and glyoxal oxidase. Finally, recent efforts on heterologous expression
      of lignin-degrading enzymes are discussed.

PMID- 9177047
TI  - Evaluation of 515 expressed sequence tags obtained from guard cells of Brassica
      campestris.
AB  - As an attempt to examine the transcripts expressed in a single cell type and to
      unveil the physiology of guard cells at the molecular level, we generated 515
      expressed sequence tags (ESTs) from a directional cDNA library constructed from
      guard-cell protoplasts of Brassica campestris L. ssp. pekinensis. A comparative
      analysis of the guard-cell ESTs against the National Center for Biotechnological
      Information non-redundant protein database revealed that 133 ESTs (26%) have
      significant similarity to protein coding sequences in the database. Among them
      were 35 clones related to genes that have not yet been identified in higher
      plants. Analysis of RNA gel blots of 14 database-matched clones revealed that
      five clones harbor the sequences for mRNAs expressed most abundantly in guard
      cells, one of them detecting an mRNA with highly preferential expression in guard
      cells. Functional categorization of the putatively identified guard-cell ESTs
      showed, when compared with maize leaf ESTs, that guard cells expressed a higher
      proportion of signal transduction components and a lower proportion of structural
      or photosynthetic genes, as is consistent with the roles of guard cells.

PMID- 9177048
TI  - Ion channels in guard cells of Arabidopsis thaliana (L.) Heynh..
AB  - Despite the availability of many mutants for signal transduction, Arabidopsis
      thaliana guard cells have so far not been used in electrophysiological research.
      Problems with the isolation of epidermal strips and the small size of A. thaliana
      guard cells were often prohibiting. In the present study these difficulties were
      overcome and guard cells were impaled with double-barreled microelectrodes.
      Membrane-potential recordings were often stable for over half an hour and voltage
      clamp measurements could be conducted. The guard cells were found to exhibit two
      states. The majority of the guard cells had depolarized membrane potentials,
      which were largely dependent on external K+ concentrations. Other cells displayed
      spontaneous transitions to a more hyperpolarized state, at which the free-running
      membrane potential (Em) was not sensitive to the external K+ concentration. Two
      outward-rectifying conductances were identified in cells in the depolarized
      state. A slow outward-rectifying channel (s-ORC) had properties resembling the
      K(+)-selective ORC of Vicia faba guard cells (Blatt, 1988, J Membr Biol 102: 235
      246). The activation and inactivation times and the activation potential, all
      depended on the reversal potential (Erev) of the s-ORC conductance. The s-ORC was
      blocked by Ba2+ (K1/2 = 0.3-1.3 mM) and verapamil (K1/2 = 15-20 microM). A second
      rapid outward-rectifying conductance (r-ORC) activated instantaneously upon
      stepping the voltage to positive values and was stimulated by Ba2+. Inward
      rectifying channels (IRC) were only observed in cells in the hyperpolarized
      state. The activation time and activation potential of this channel were not
      sensitive to the external K+ concentration. The slow activation of the IRC (t1/2
      approximately 0.5 s) and its negative activation potential (Vthreshold = -155 mV)
      resemble the values found for the KAT1 channel expressed in Saccharomyces
      cerevisiae (Bertl et al., 1995, Proc Natl Acad Sci USA 92: 2701-2705). The
      results indicate that A. thaliana guard cells provide an excellent system for the
      study of signal transduction processes.

PMID- 9177049
TI  - A novel proline-rich glycoprotein associated with the extracellular matrix of
      vascular bundles of Brassica petioles.
AB  - A panel of monoclonal antibodies (MAC204, MAC236, MAC265) which recognise
      extracellular matrix glycoproteins implicated in plant-microbe interactions has
      been used to study glycoprotein antigens in petioles of turnip (Brassica
      campestris L.). While MAC204 recognised two glycoproteins (gp120 and gp45) with
      apparent M(r) 120,000 and 45,000 in petiole extracts made with 2-amino-2
      (hydroxymethyl)-1,3-propanediol (Tris) buffer containing sodium dodecyl sulfate,
      MAC236 recognised gp120 but not gp45, and MAC265 gave no or only weak reactivity.
      Tissue dissection studies established that gp120 was predominantly associated
      with the vascular bundle whereas gp45 was largely associated with the pith. This
      was consistent with results from tissue prints probed with MAC204 and MAC236
      which also suggested a vascular localisation for gp120. Immunoelectronmicroscopy
      showed that MAC204 and MAC236 both labelled three-way junctions between cells of
      the phloem and sclerid fibres. Both gp120 and gp45 were shown to carry epitopes
      in common with known hydroxyproline-rich glycoproteins. Unlike gp45, gp120 could
      be extracted from petioles with Tris buffer alone and then isolated from this
      extract by trichloroacetic acid treatment (which left gp120 soluble), followed by
      size-exclusion and ion-exchange chromatography. Amino acid analysis revealed
      gp120 to be a novel glycoprotein, particularly rich in proline, lysine, valine
      and threonine but relatively poor in hydroxyproline. The most abundant sugars
      were arabinose and galactose. The potential role of this very basic cell surface
      glycoprotein in plant defence against microbes is discussed.

PMID- 9177050
TI  - Cristal mutations in Arabidopsis confer a genetically heritable, recessive,
      hyperhydric phenotype.
AB  - A new class of recessive Arabidopsis mutants, designated cristal (cri) has been
      isolated which display several abnormalities reminiscent of hyperhydric symptoms.
      These characteristics include translucent and wrinkled cotyledons and leaves,
      abnormal chloroplast organization, a reduced amount of chlorophyll, a reduced dry
      weight and a decreased number of palisade cells in the leaves accompanied by an
      increase of intercellular space, and therefore give a vitreous appearance to the
      aerial part. The phenotype is also dependent on the culture medium water
      potential. The cri1 gene was mapped on chromosome 4 close to the DHS1 marker.

PMID- 9177051
TI  - A comparison of two-dimensional electrophoresis data with phenotypical traits in
      Arabidopsis leads to the identification of a mutant (cri1) that accumulates
      cytokinins.
AB  - Total proteins extracted from developmental mutants of Arabidopsis thaliana (L.)
      Heyhn. and from wild-type plants cultivated in the presence of various hormones
      were analyzed by two-dimensional (2-D) gel electrophoresis. Computer analysis of
      2-D gels followed by a statistical treatment of data allowed us to build a
      phenogram that describes the biochemical distances between the different
      genotypes. Analysis of the 2-D electrophoresis data allowed us to discriminate
      mutants in agreement with phenotypical and physiological traits. This biochemical
      analysis helped us to develop a working hypothesis which led us to show that one
      developmental mutant (cri1) overaccumulates cytokinins.

PMID- 9177052
TI  - Pectin methylesterases from poplar cambium and inner bark: localization,
      properties and seasonal changes.
AB  - In the course of a study on the early events of cambial derivative
      differentiation in Populus x euramericana, seasonal changes in the pattern of
      pectin methylesterase (PME, EC 3.1.1.11) isoforms were followed. During the
      resting season, cell wall extracts contained mainly alkaline isoforms with an
      M(r) around 55 kDa and optimal pH between 5.6 and 6.0. Neutral isoforms with an
      M(r) around 35 kDa and optimal pH between 6.0 and 6.6 predominated in the
      extracts during the period of high meristematic activity. In the active cambial
      initials and in their immediate derivatives, the enzymes were immunolocalized
      exclusively in the dictyosomes. In older cells, they were present both in
      dictyosomes and in wall junctions. These results indicate that exportation of
      neutral PMEs towards the walls might be considered as an early marker of
      differentiation in cambial derivatives.

PMID- 9177053
TI  - Characterisation and cloning of a calmodulin-like domain protein kinase from
      Chlamydomonas moewusii (Gerloff).
AB  - Calcium-stimulated protein kinase activity in the flagella of the green alga
      Chlamydomonas moewusii (Gerloff) was characterised. Using SDS-PAGE and an on-blot
      phosphorylation assay, a 65-kDa protein was identified as the major calcium
      stimulated protein kinase. Its activity was directly stimulated by calcium, a
      characteristic of the calmodulin-like domain protein kinases (CDPKs). Monoclonal
      antibodies raised against the CDPK alpha from soybean cross-reacted with the 65
      kDa protein in the flagella, and also with other proteins in the flagellum and
      cell body. The same monoclonal antibodies were used to screen a C. moewusii cDNA
      expression library in order to isolate CDPK cDNAs from C. moewusii. The CCK1 cDNA
      encodes a protein with a kinase and calmodulin-like domain linked by a junction
      domain typical of CDPKs. From Southern analyses, evidence was obtained for a CDPK
      gene family in C. moewusii and C. reinhardtii.

PMID- 9177054
TI  - Localisation of sucrose-phosphate synthase and starch in leaves of C4 plants.
AB  - The activity and intercellular distribution of sucrose-phosphate synthase (SPS;
      EC 2.4.1.14) were determined in fully expanded leaves from a range of C4 plants.
      In Zea mays L. and Atriplex spongiosa F. Muell., SPS was located almost
      exclusively in the mesophyll cells. In other species, SPS was found in both cell
      types, with the activity in the bundle sheath cells ranging from 5% of the total
      leaf activity in Echinochloa crus-galli (L.) Beauv. to 35% in Sorghum bicolor
      Moench. At the end of the light period, starch was found only in the bundle
      sheath cells in all of the species examined. There appears to be little
      correlation between C4-acid decarboxylation type and the location of sucrose and
      starch synthesis in the leaves of C4 plants.

PMID- 9177055
TI  - 3-Hydroxybenzoate:coenzyme A ligase and 4-coumarate:coenzyme A ligase from
      cultured cells of Centaurium erythraea.
AB  - 3-Hydroxybenzoate:coenzyme A ligase, an enzyme involved in xanthone biosynthesis,
      was detected in cell-free extracts from cultured cells of Centaurium erythraea
      Rafn. The enzyme was separated from 4-coumarate:coenzyme A ligase by fractionated
      ammonium sulphate precipitation and hydrophobic interaction chromatography. The
      CoA ligases exhibited different substrate specificities. 3
      Hydroxybenzoate:coenzyme A ligase activated 3-hydroxybenzoic acid most
      efficiently and lacked affinity for cinnamic acids. In contrast, 4-coumarate:CoA
      ligase mainly catalyzed the activation of 4-coumaric acid but did not act on
      benzoic acids. The two enzymes were similar with respect to their relative
      molecular weight, their pH and temperature optima, their specific activity and
      the changes in their activity during cell culture growth.

PMID- 9177056
TI  - Intracellular distribution and identification of the nuclear localization signals
      of two plant heat-stress transcription factors.
AB  - Similar to heat-stress transcription factors (HSFs) from non-plant sources, HSFA1
      and HSFA2 from tomato (Lycopersicon esculentum Mill) contain two conserved
      clusters of basic amino acid residues (K/R1 and K/R2) which might serve as
      nuclear localization signal (NLS) motifs. Mutation of either one of them and
      functional testing of the corresponding proteins in a transient expression assay
      using tobacco (Nicotiana plumbaginifolia L:) protoplasts gave the following
      results. Whereas K/R1, positioned in all HSFs at the C-terminus of the DNA
      binding domain, had no influence on nuclear import, the K/R1 mutants were
      impaired in their interaction with the DNA (band-shift assays). In contrast to
      this, mutants of the K/R2 motif, found 15-20 amino acid residues C-terminal of
      the oligomerization domain (HR-A/B region), had wild-type activity in DNA-binding
      but were defective in nuclear import. Thus, for the related tomato HSFA1 and
      HSFA2 the K/R2 cluster represents the only NLS motif, and in this function it
      cannot be replaced by K/R1.

PMID- 9177058
TI  - Evidence-based treatment for drug misuse: bridging the gap between aspiration and
      achievement.

PMID- 9177057
TI  - Solute accumulation and decreased photosynthesis in leaves of potato plants
      expressing yeast-derived invertase either in the apoplast, vacuole or cytosol.
AB  - Potato (Solanum tuberosum cv. Desiree) plants expressing yeast invertase directed
      either to the apoplast, vacuole or cytosol were biochemically and physiologically
      characterised. All lines of transgenic plants showed similarities to plants
      growing under water stress. Transformants were retarded in growth, and
      accumulated hexoses and amino acids, especially proline, to levels up to 40-fold
      higher than those of the wild types. In all transformants rates of CO2
      assimilation and leaf conductance were reduced. From the unchanged intercellular
      partial pressure of CO2 and apoplastic cis-abscisic acid (ABA) content of
      transformed leaves it was concluded that the reduced rate of CO2 assimilation was
      not caused by a limitation in the availability of CO2 for the ribulose-1,5
      bisphosphate carboxylase-oxygenase (Rubisco). In the transformants the amount of
      Rubisco protein was not reduced, but both activation state and carboxylation
      efficiency of photosynthesis were lowered. In vacuolar and cytosolic
      transformants this inhibition of Rubisco might be caused by a changed ratio of
      organic bound and inorganic phosphate, as indicated by a doubling of
      phosphorylated intermediates. But in apoplastic transformants the pattern of
      phosphorylated intermediates resembled that of leaves of water-stressed potato
      plants, although the cause of inhibition of photosynthesis was not identical.
      Whereas in water-stressed plants increased contents of the phytohormone ABA are
      supposed to mediate the adaptation to water stress, no contribution of ABA to
      reduction of photosynthesis could be detected in invertase transformants.

PMID- 9177059
TI  - Alcohol interventions: do the best things come in small packages?
AB  - Several extensive reviews have highlighted the effectiveness of brief alcohol
      interventions. The same reviews were pessimistic about the role of more
      intensive, specialist treatments. It is argued here that the research evidence
      should be interpreted with caution. There are problems of generalizability of the
      research, and studies focusing on brief interventions in the primary health care
      field are largely not comparable with clinical trials conducted in the specialist
      setting. The efficacy of brief interventions as a routine mass intervention
      approach has been exaggerated. Even after extensive research, little is known of
      the effective ingredients and the most effective methods of delivery. Reviews of
      brief interventions have been overly selective, and meta analysis in this area is
      problematic. It is argued that such reviews lead to overgeneralization and turn
      attention away from promising specialist treatment approaches. More research is
      needed into identifying the target group most likely to benefit from brief
      interventions, cost effectiveness, and into shared care and stepped care
      approaches, before embarking on a major shift in treatment policy towards brief
      interventions.

PMID- 9177060
TI  - The efficacy of disulfiram: a review of outcome studies.
AB  - Twenty-four studies of outcome following oral disulfiram and 14 following
      implanted disulfiram were identified for review from MEDLINE and PsycINFO
      databases and by manual searching for the period 1967-95. The methodological
      rigour of these studies was generally poor, albeit not as poor as that of earlier
      studies (not reviewed here). An overall assessment of the results of research in
      this field is hampered by the diversity of both the methods used and the subject
      populations studied. However, it is clear that support for the general use of
      oral disulfiram is equivocal, mostly being found in the form of reduced quantity
      of alcohol consumed and a reduced number of drinking days. Evidence for an effect
      in increasing the proportion of patients who achieve abstinence is surprisingly
      lacking. Where it is prescribed, disulfiram use should be supervised and it
      should be employed as one part of a comprehensive treatment programme. There is
      no good evidence in favour of implanting disulfiram tablets, but the possibility
      of a depot injection is intriguing.

PMID- 9177061
TI  - Co-factors for smoking and evolutionary psychobiology.
AB  - Smoking is becoming increasingly concentrated in people with co-factors such as
      depression, attention deficit-hyperactivity disorder, anxiety disorders, and
      bulimia/bingeing. These behavioral or cognitive patterns may be adaptive or
      neutral in the conditions under which we evolved but maladaptive in environments
      requiring alertness for extended periods, where a fully mobilized fight-or-flight
      response is inappropriate, and where food availability makes lack of an
      "appestat" a liability. Such conditions are amenable to management by nicotine
      because of its ability to produce small but reliable adjustments in relevant
      cognitive and behavioral functions. Moreover, symptomatology may be unmasked or
      exacerbated by nicotine abstinence, persisting beyond the usual time-course for
      nicotine withdrawal, which may explain the particular attraction of smoking and
      the difficulty these individuals experience in quitting without necessarily
      requiring that they be more nicotine-dependent. The implications are: (1) a
      better understanding of the evolutionary psychobiology of smoking may promote
      development of tailored interventions for smokers with co-factors; (2) nicotine
      may have therapeutic applications for non-smokers with co-factors; (3) because
      smoking has a fairly high heritability index, and because of evidence of
      assortative mating, special prevention efforts targeting children of smokers with
      co-factors, as well as early identification of the co-factor itself, may be
      needed.

PMID- 9177062
TI  - How do genes influence marijuana use? The role of subjective effects.
AB  - This study investigated determinants of the subjective effects of marijuana and
      the relationship of subjective effects to marijuana use. Subjects were 8169 twins
      drawn from the Vietnam Era Twin Registry. Subjects who used marijuana more than
      five times (n = 2513) reported whether they experienced each of 23 subjective
      reactions. Factor analysis identified a positive (pleasant) reaction factor and a
      negative (unpleasant) reaction factor. Both factors were related to duration and
      frequency of use. Pairs in which both members used marijuana more than five times
      (MZ = 352 pairs; DZ = 255 pairs) were examined to assess determinants of
      subjective effects. Approximately one-quarter of the variance in each factor was
      determined by additive genetic influences; the remaining variance was determined
      by environmental factors that are not shared by members of a twin pair. The
      shared or family environment had no detectable influence on either subjective
      reaction factor.

PMID- 9177063
TI  - Mortality and survival among a cohort of drug injectors in Glasgow, 1982-1994.
AB  - There has been much speculation about the nature and extent of mortality among
      drug injectors in Glasgow. In order to determine injectors' mortality rate and
      compare this rate to the general population, identifier information from 459 drug
      injectors who received treatment for drug misuse in Glasgow between 1982 and 1994
      was linked to the Scottish Mortality Register. The average duration of follow-up
      from cohort entry was 5.5 years and 10.2 years from commencement of drug
      injection. By the end of 1994, 53 cohort members had died. The average annual
      mortality rate of 1.8% was the same as that observed in a London cohort followed
      up from 1969 to 1991. However, the excess mortality ratio (EMR) of 22.0 was
      almost double the London rate (11.9) because of the much lower average age of
      mortality (26.3 vs. 38.2 years). There was no significant time trend in EMR.
      Kaplan-Meier hazard analyzes show that younger patients and those who were HIV
      positive had significantly elevated mortality rates. The main cause of death was
      overdose, although it is unclear how many were accidental and how many
      intentional. Three of the six fatalities among HIV positive injectors were AIDS
      related. This study enables the first realistic assessment of the hypothesis that
      drug-related deaths in Glasgow are especially high. In relation to other
      populations of drug injectors, the annual mortality rate is comparable, although
      the average age of mortality is much lower in Glasgow. Consequently, in
      comparison to the general population, the mortality rate of drug injectors is
      higher in Glasgow compared to other cities.

PMID- 9177064
TI  - Drug abusers in Danish mental hospitals.
AB  - The purpose of this study was to investigate trends in drug abuse among
      psychiatric inpatients in Denmark. The investigation was based on data collected
      from The Danish Psychiatric Case Register. The findings show that drug abusers
      occupy an increasing number of beds in Danish psychiatric hospitals and
      departments. Moreover, an increase in the number of patients with schizophrenic
      or borderline diagnoses combined with drug abuse was found. Furthermore, the drug
      abuse found among psychiatric patients now is frequently more serious than
      previously. Finally, an increased number of young males admitted with drug abuse
      was discovered. Young males are also more frequently diagnosed as illegal, or
      polydrug abusers, as opposed to older males and females.

PMID- 9177065
TI  - Substance abuse and homelessness: social selection or social adaptation?
AB  - Although substance abuse has for many years been documented as a serious problem
      among homeless populations, there is as yet no clear understanding of the nature
      of the relationship between substance abuse and homelessness. We evaluate
      alternative social selection and social adaptation models of this process. Using
      data from a random probability sample, the substance abuse and homeless
      experiences of 303 homeless people and people at risk of homelessness in Cook
      County, Illinois, were investigated. Proportional hazards regression models were
      employed to assess both social selection and social adaptation models. Drug but
      not alcohol abuse was associated with first homeless episode. Prior homeless
      experiences were found to be predictive of first symptoms of both alcohol and
      drug abuse. Other variables, including the availability of social and economic
      resources, were also associated with each of these outcomes. Models of both
      selection and adaptation processes are necessary to account for the association
      between homelessness and substance abuse, indicating that a multi-directional
      model is more appropriate. In addition findings suggest that, in recent years,
      drugs may have displaced alcohol as an important precursor of homelessness for
      many individuals.

PMID- 9177066
TI  - A longitudinal study of social, psychological and behavioural factors associated
      with drunken driving and public drunkenness.
AB  - Studies on psychosocial conditions in drunken drivers have generally been cross
      sectional and based on rather small selected samples. The objective of this study
      was to analyse, in a longitudinal perspective, the relationship, in young males,
      between social and psychological factors and indicators of alcohol abuse on one
      hand and the risk of subsequent drunken driving and public drunkenness on the
      other hand, in order to identify similarities and differences in risk factor
      patterns. Questionnaire information from 8122 military conscripts in 1969/70 was
      linked to data on drunken driving and public drunkenness for 495 males with
      offences registered up to 1977. Logistic regression analysis showed that the
      relative risk (RR) for high alcohol consumption, smoking, use of narcotics and
      sniffing of solvents had a statistically significant association to subsequent
      drunken driving and public drunkenness in univariate analyses. In multivariate
      logistic analyses, RR remained increased for those with fathers belonging to
      social class II and especially so for those coming from social class III. Smoking
      (RR 3.3, with a 95% confidence interval of 1.6-6.8) was significantly increased
      in drunken drivers with a blood alcohol concentration (BAC) of 0.15% or more at
      apprehension, as was truancy or contact with police or juvenile authorities in
      drunken drivers with a BAC of 0.05-0.15%, and illicit drug use, intoxication
      drinking, contact with police or juvenile authorities and hangover with public
      drunkenness. Thus, we found that early social and behavioural factors, substance
      abuse and risky use of alcohol were predictors for both drunken driving and
      public drunkenness, with no marked differences in risk factor patterns.

PMID- 9177067
TI  - Community psychiatric nurse aftercare for alcoholics: a five-year follow-up
      study.
AB  - The aim of this study was to determine if community psychiatric nurse (CPN)
      aftercare for 1 year improved the 5-year outcome in patients following inpatient
      treatment for alcohol dependence. A 5-year follow-up study, observer blind, with
      non-random allocation of subjects to aftercare by CPN for 1 year or standard
      outpatient care, was used. Subjects had all received inpatient treatment for 6
      weeks in a rural alcohol treatment unit. Subjects were traced and assessed in the
      community 5 years after the index admission. The participants consisted of 127
      white male alcoholics. All were first admissions, who had been selected for
      inpatient treatment and who completed a 6-week inpatient stay. Seventy-three
      subjects received intensive aftercare by CPN for 1 year, 54 subjects received
      standard outpatient appointments not due to random allocation but because no CPN
      was available. Data were collected by semi-structured interview at entry to the
      trial, namely background epidemiological information, details of drinking
      history, previous hospital admission, educational, employment and criminal
      information. At 5-year follow-up, data on drinking status, use of other drugs,
      hospital admissions, criminal behaviour and gambling, attendance at self-help
      groups, relationships and employment were collected. Thirty-six per cent of the
      CPN aftercare group was completely abstinent during the 5 years after treatment
      compared to 6% of the standard aftercare group (p < 0.001). Subjects receiving
      CPN aftercare were less likely to report blackouts (p < 0.05) or gambling (p <
      0.05). They were more likely to attend hospital meetings (p < 0.0001). CPN
      aftercare is an effective way of maximizing the effects of inpatient treatment.
      The effects endured for 5 years after treatment.

PMID- 9177068
TI  - Assessing the generalizability of smoking studies.
AB  - We used data from the 1986 Adult Use of Tobacco Survey, 10 studies of self
      quitters and seven studies of treatment seekers, to illustrate how subpopulations
      of smokers might differ; e.g. treatment seekers vs. self-quitters and research
      volunteers vs. smokers in the general population. Smoking researchers may wish to
      use our results to determine whether their sample is similar to the population of
      interest.

PMID- 9177069
TI  - Adult smokers who do not smoke daily.
AB  - Almost 20% of Californian smokers do not smoke daily. Although occasional (non
      daily) smoking occurs during uptake, a stable pattern of occasional smoking may
      imply a milder level of nicotine addiction. We use a longitudinal population
      sample of smokers interviewed in both 1990 and 1992 to evaluate the stability of
      occasional smoking. Further, we use 1992 data, including smokers only interviewed
      in 1992, to compare occasional smokers who have (ever-daily) and have not (never
      daily) smoked daily for at least 6 months, and contrast them to daily smokers for
      key variables associated with addiction. All our analyses exclude uptake smokers.
      Two-thirds of never-daily occasional smokers in 1992 also smoked occasionally in
      1990, compared to only about 40% of ever-daily occasional smokers. Never-daily
      occasional smokers smoke less than ever-daily ones. They are more often under age
      40 years, of Hispanic origin, and were more likely to begin regular smoking
      beyond their teen years. Demographically, ever-daily occasional smokers were
      similar to daily smokers except for being more educated. However, both ever-daily
      and never-daily smokers differed from daily smokers with respect to long-term
      quitting history, plans to quit, confidence they could quit, and belief they are
      addicted to cigarettes. Our findings suggest that occasional smoking can be a
      stable pattern for long periods. Occasional smokers, particularly never-daily
      ones, appear to be much less addicted to nicotine than daily smokers.

PMID- 9177070
TI  - How to become a true scientist: a guide to minimizing pesky treatment effects.

PMID- 9177071
TI  - How to measure outcome in alcoholism treatment studies?

PMID- 9177073
TI  - Should there be aromatherapy for addiction?

PMID- 9177072
TI  - How to have a high success rate in treatment.

PMID- 9177074
TI  - Self-assembled monolayers for biosensors.
AB  - The use of self-assembled monolayers (SAMs) in various fields of research is
      rapidly growing. In particular, many biomedical fields apply SAMs as an interface
      layer between a metal surface and a solution or vapour. This review summarises
      methods for the formation of SAMs upon the most commonly used materials and
      techniques used for monolayer characterisation. Emphasis will lie on uniform,
      mixed and functionalised monolayers applied for immobilisation of biological
      components including (oligo-)nucleotides, proteins, antibodies and receptors as
      well as polymers. The application of SAMs in today's research, together with some
      applications will be discussed.

PMID- 9177075
TI  - Application of tryptamine as a derivatizing agent for the determination of
      airborne isocyanates. Part 7. Selection of impinger solvents and the evaluation
      against dimethyl sulfoxide used in US NIOSH Regulatory Method 5522.
AB  - The application of tryptamine to derivatize airborne isocyanates has been
      evaluated and adopted by the National Institute for Occupational Safety and
      Health (NIOSH) as the latest isocyanates regulatory method (Method 5522) in the
      USA. Method 5522 uses dimethyl sulfoxide (DMSO) as the impinger solvent in which
      tryptamine is dissolved to sample isocyanates for analysis. Since DMSO is both
      extremely hygroscopic and corrosive, it is not a satisfactory solvent for
      impinger air sampling of isocyanates. The high boiling and freezing points also
      present some distinct drawbacks. In a search for a suitable impinger solvent, the
      efficiencies of various solvents, which all were potentially more suitable for
      sampling isocyanates viz., N,N'-dimethylformamide, butyl acetate, isobutyl
      acetate, sec-butyl acetate, tert-butyl acetate and octane, were investigated.
      Simulated air sampling was conducted on two commonly used isocyanates in
      industry, hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI), which
      were vaporized and sampled into impingers containing dissolved tryptamine. Butyl
      acetate and octane were found to be most suitable for using as impinger solvents.
      Recoveries of isocyanates at two concentration levels of HDI and TDI were 93.4
      108% in comparison with those of using DMSO.

PMID- 9177076
TI  - Determination of cadmium in environmental samples by hydride generation with in
      situ concentration and atomic absorption detection.
AB  - A volatile Cd species (presumed to be the hydride) was generated from aqueous
      solutions by merging sample and tetrahydroborate reductant in a continuous-flow
      system. The gaseous analyte was transferred onto the inner wall of a graphite
      tube furnace for in situ preconcentration at 200 degrees C. Calibration was
      achieved via the method of standard additions. An absolute detection limit (3
      sigma blank) of 10 pg was obtained using KBH4 as reductant. The precision of the
      determination was 12% (RSD) for a Cd concentration of 0.2 ng ml-1 using KBH4. The
      method was successfully applied to the determination of Cd in several certified
      environmental reference materials (soil, sediment, sea-water, biological samples)
      following pressure digestion of the samples by microwave heating in a mixture of
      acids.

PMID- 9177077
TI  - Flow injection spectrophotometric determination of L-Dopa and carbidopa in
      pharmaceutical formulations using a crude extract of sweet potato root [Ipomoea
      batatas (L.) Lam.] as enzymatic source.
AB  - A flow injection (FI) spectrophotometric method is proposed for the determination
      of L-dopa and carbidopa in pharmaceutical formulations. After selection of the
      extraction medium (e.g., buffer-to-tissue ratio, pH, buffer concentration,
      protective agents and/or stabilizers) and storage conditions, crude extract of
      sweet potato root [Ipomoea batatas (L.) Lam.] was used as an enzymatic source of
      polyphenol oxidase (Tyrosinase; catechol oxidase; EC.1.14.18.1) directly in the
      carrier. This enzyme catalyses the oxidation of these catecholamines to the
      corresponding dopaquinone. Further, dopaquinone undergoes a rapid spontaneous
      auto-oxidation to leucodopachrome, which is in turn oxidized to dopachrome; this
      last compound has a strong absorption at 480 and 360 nm for L-dopa and carbidopa,
      respectively. For the optimum extraction conditions found the enzyme activity of
      the crude extract did not vary for at least 5 months when stored at 4 degrees C
      and decreased by only 4-5% during an 8 h working period at 25 degrees C. The
      results obtained for L-dopa and carbidopa by the proposed enzymatic FI method
      were in close agreement with the label values (r1 = 0.9699 and r2 = 0.9999) and
      also with those obtained using a pharmacopeial method (r3 = 0.9675). The
      throughput was 26 samples h-1, and 2.30 ml of crude extract were consumed in each
      determination, corresponding to only 72 mg of the original sweet potato root. The
      detection limit (three times the signal blank/slope) was 1.5 x 10(-5) and 2.0 x
      10(-5) mol l-1 for L-dopa and carbidopa, respectively; the recovery of L-dopa and
      carbidopa from three samples ranged from 98.6 to 106.3% of the added amount.

PMID- 9177078
TI  - Simultaneous determination of the colorants sunset yellow FCF and quinoline
      yellow by solid-phase spectrophotometry using partial least squares multivariate
      calibration.
AB  - A method for the simultaneous determination of the colorants Sunset Yellow FCF
      and Quinoline Yellow using solid-phase spectrophotometry is proposed. The
      colorants were isolated in Sephadex DEAE A-25 gel at pH 5.0, the gel-colorants
      system was packed in a 1 mm silica cell and spectra were recorded between 400 and
      600 nm against a blank. Statistical results were obtained by partial least
      squares (PLS) multivariate calibration. The optimized matrix by using the PLS-2
      method enables the determination of the colorants in artificial mixtures and
      commercial soft drinks.

PMID- 9177079
TI  - Intrinsic molecular fluorescence of lactate dehydrogenase: an analytical
      alternative for enzymic determination of pyruvate.
AB  - A method for the enzymic determination of pyruvate based on changes in the
      fluorescence intensity of lactate dehydrogenase (LDH) is described. These changes
      are due to the differential quenching effect produced by NAD and NADH on the LDH
      fluorescence. The NADH quenching is due to both an inner filter effect and LDH
      NADH complex formation; the LDH-NADH complex is also fluorescent. However, the
      NAD quenching is based only on the inner filter effect. From these suppositions,
      the equilibrium constant of the reaction and the formation constant of the LDH
      NADH complex were obtained. Given this, an appropriate analytical signal for the
      quantification of pyruvate and a mathematical model explaining the effect of each
      parameter are proposed. The linear response range of the method depends on the
      NADH concentration used during the determination; it is possible to determine
      pyruvate concentrations down to 8.8 x 10(-7) mol dm-3. The method was applied to
      the determination of pyruvate in synthetic blood samples with good accuracy.

PMID- 9177080
TI  - Enhancement of Rayleigh light scattering of acid chrome blue K by proteins and
      protein assay by the scattering technique.
AB  - Rayleigh light scattering of Acid Chrome Blue K (ACBK) is enhanced greatly by
      proteins. Based on this, a method for protein assay in aqueous solution was
      developed. This assay matches the sensitivity of the colorimetric dye-binding
      method with a linear range of 0.136-10.88 micrograms ml-1. The measurements can
      be made easily on a common fluorimeter. The reaction between ACBK and proteins is
      completed in 2 min and the scattered light signal is stable for at lest 3 h.
      Protein-to-protein variability is encountered in this method as in many other
      protein assays. There is little or no interference from amino acids, most metal
      ions and complexing agents (e.g., EDTA). Interferences from salts, urea and
      detergents can be minimized by dilution.

PMID- 9177081
TI  - Evaluation of systems for anaerobe identification.

PMID- 9177082
TI  - Clinical significance of tooth morphology correlated with periodontal disease-I.
AB  - Anatomical abnormalities of tooth and root morphology may not only adversely
      influence the course and management of periodontal disease due to inaccessibility
      of periodontal instrumentation and oral hygiene efforts, but are also more likely
      to adversely become high risk areas for retention of dental plaque and calculus.
      This article reviewed the results of data on the root morphology and comparative
      literature associated with prevalence, anatomical considerations and clinical
      significance in the predisposing factors to the periodontal disease. The purpose
      was to emphasize the importance of understanding the knowledge concerning the
      variations of tooth and/or root anatomy as a high risk factor for periodontal
      disease and as a necessary tool for the prognosis, diagnosis and treatment of
      existing or potential periodontal disease.

PMID- 9177083
TI  - Liposomes-coated hydroxyapatite and tricalcium phosphate implanted in the
      mandibular bony defect of miniature swine.
AB  - Hydroxyapatite and tricalcium phosphate have been used as bone implants for some
      period of time. Now unfortunately, these materials have failed to become the
      nucleation sites for bone regeneration. We hypothesized that coating
      hydroxyapatite and tricalcium phosphate with negatively charged liposomes may
      improve the nucleation process for new bone formation. The present study was
      designed to test this hypothesis. Experiments were carried out in 15 miniature
      swines' mandibular angle with artificial bony defects. In each of the swine, the
      bony defects on one side were implanted with either liposomes coated with
      hydroxyapatite or liposomes coated with tricalcium phosphate, while the other
      side served as control. At the end of the third and sixth weeks following the
      operation, we observed result, took histology and radiographs of the operated
      area. The results showed that liposomes-coated materials were biocompatible and
      their clinical endpoint was enhanced. At the end of the third week, the implant
      material was surrounded by dense connective tissues. At the end of the sixth
      week, there were new bone formations near the implanted material. In addition,
      liposomes which were immobilized in agarose gel and implanted in the defects
      showed new bony bridge formation. These observations suggest that liposomes have
      the ability in promoting repair of osseous deficiencies.

PMID- 9177084
TI  - An analysis of intraspinal tumors in south Taiwan.
AB  - A series of 120 pathologically verified intraspinal tumors was analyzed for the
      relative incidence and location of the tumors as well as the distribution of age
      and sex. These data were compared to series from Taiwan, mainland China,
      Thailand, Korea, Japan, Iran, India, and countries in the West. The ratio of
      brain to intraspinal tumors was about 5:1 in Taiwan, higher than those reported
      in China, Korea, and in the West. The male to female ratio is about six to five.
      For most tumors, male predominance is noted except for meningioma. The incidence
      of intraspinal tumors in the order of frequency is nerve sheath cell tumor(NSCT),
      metastatic tumors, meningioma, glioma, congenital tumors, and vascular tumors. In
      the East, the incidence of NSCT is about 40%, and meningioma is about 10%. In the
      West, they are both about 20%. Congenital tumors accounted for only 3.3%. In
      China, it was about 12% and this is the highest incidence of dysembryoplastic
      tumors in the world. Glioma has similar incidence (about 10%) in Taiwan, China,
      Thailand, Japan, and Iran (about 10%), whereas it is about 15% in the West and
      India. Korea has the highest incidence of glioma, (32.3%). Low incidences of
      metastatic intraspinal tumors (4.6-5.5%) were noted in China and Japan, but a
      higher incidence (14.2-24.2%) was seen in Taiwan, Iran, and the West. The most
      common metastatic tumors in the order of frequency is tumors of unknown origin,
      lung cancer metastasis, hepatoma, and breast cancer. The high percentage of
      unknown origin of metastasis may have resulted from loss of follow-up and lack of
      postmortem studies.

PMID- 9177085
TI  - Nontraumatic intracerebral hemorrhage in young adult.
AB  - We reviewed our experience with 91 patients aged 15 to 40 years with nontraumatic
      intracerebral hemorrhage (ICH) from January 1991 through December 1994 and found
      more than ten presumed causes for the nontraumatic ICH in 68 patients (74.7%).
      The leading two causes were arterial hypertension and ruptured arteriovenous
      malformations. Most cases of ICH were lobar and putaminal. Of the lobar
      hemorrhages, 26.5% resulted from ruptured arteriovenous malformations. Of the
      putaminal hemorrhages, we found 60% resulted from arterial hypertension.
      Arteriography was performed in 36 patients, and was diagnostic in 23. A history
      of drug abuse was found in 3 patients. The survival rate was 82.4% at 1 month,
      78.0% at 6 months and 76.9% at 1 year. The in-hospital survival rate of all
      patients in this study was 78.0%. The outcome was determined at one month after
      hemorrhage. Thirty-two percent of our cases made a good recovery (back to
      normality), 35% a fair recovery (moderately disabled but independent), 15% a poor
      recovery (severely disabled and dependent), and 18% died. Arterial hypertensive
      hemorrhage accounted for almost 30% of our young ICH patients which reminds us of
      the importance of regular control of blood pressure even in the young adults.
      Arteriography performed early in the course of nontraumatic ICH in young adults,
      particularly in lobar hemorrhages, is a valuable adjunct in determining cause.
      Although the details of history of drug abuse were frequently lacking, physicians
      should keep this abuse in mind as a possible cause for nontraumatic ICH.

PMID- 9177086
TI  - The relationship between health locus of control and compliance of hemodialysis
      patients.
AB  - Successful treatment of end stage renal disease (ESRD) depends on the patient
      compliance with therapeutic regimens. This descriptive study was conducted to
      examine the relationship between the health locus of control (HLC) orientation
      and compliance with therapeutic regimens. The convenience sample of 86
      hemodialysis patients was obtained at two hemodialysis centers of teaching
      hospitals in southern Taiwan. A Demographic Questionnaire, the Multidimensional
      Health Locus of Control (MHLC) Scale, and Multimethod Compliance Assessment
      (including: Laboratory Assessment, Nurse Assessment, and Patient Self-report)
      were used to collect the data. The average overall rate of compliance with
      therapeutic regimen was 76.4% by patient self-report and 69.2% by nurse
      assessment. Examining the three compliance measures, patients were most compliant
      in following instructions for taking phosphate-binding medication (PBM) and least
      compliant in limiting fluid intake according to patient self-report and by
      nurses' assessment. The level of compliance for diet restriction fell between the
      other two measures. No significant correlations between the three subscales of
      the multidimensional health locus of control (MHLC) and composite compliance
      measures were found in this study, except that those with a high score on the
      subscale of powerful others locus of control were positively correlated with
      patient self-report (r = 0.388, p < 0.001) and with the laboratory assessment (r
      = 0.21, p < 0.01). This suggests that the MHLC construct had only a slight
      influence on measures of compliance in hemodialysis patients of Taiwan.
      Implications of findings for nursing practice, theory, and research are also
      discussed.

PMID- 9177087
TI  - Couples' satisfaction with health care service during labor and delivery.
AB  - The purpose of this study was to examine consumer satisfaction with health care
      service during labor and delivery. An exploratory study was conducted by
      obtaining information from 191 couples who were hospitalized at one medical
      center in southern Taiwan. A Consumer Satisfaction Questionnaire with three
      additional open questions developed by the authors and a Social Support Scale
      modified from the Family APGAR Index were administered. Factor analysis
      identified the following three factors most often associated with consumers'
      satisfaction with labor and delivery during hospitalization: (1) the Supply of
      Equipment, (2) the Participants in the Delivery and (3) the Management of the
      Ward. Moreover, the level of couples' satisfaction with hospitalization during
      labor and delivery was significantly correlated with high professional support.
      Suggestions are also made for future efforts in quality of care and consumer
      satisfaction.

PMID- 9177088
TI  - The psychiatric manifestation of Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is considered to be very rare in the population,
      and the psychiatric manifestation of the disease even rarer with only one report
      in the past few years in Taiwan. To clarify whether the psychiatric manifestation
      of CJD is really rare or whether it is neglected in Taiwan, the authors reviewed
      the discharge notes of patients who had been admitted to a neurological unit in
      the past 15 years and conducted a chart review of the patients of CJD supported
      by the clinical courses, EEG finding and brain biopsies. An inquiry was made by
      telephoning their families to follow up their condition after discharge. Five of
      the 8 cases with CJD had psychiatric symptoms including changes of mood, thought,
      behavior and perception during their course of illness. Four cases had been sent
      to the psychiatric unit and received treatment under several kinds of psychiatric
      diagnoses. Two patients had been admitted to the psychiatric unit and one had
      received electroconvulsive treatment. Two of the patients had been suspected to
      be the victims of neuroleptic malignant syndrome. It is likely that it is
      psychiatrists who will meet CJD patients first in the early stages of disease.
      CJD should be kept in mind and EEGs with detailed neurological checkups should be
      completed, if the cognitive functions of the patients with unusual neurological
      symptoms deteriorate quickly and their psychiatric symptoms fail to respond to
      any treatment.

PMID- 9177089
TI  - The familial occurrence of brain tumors.
AB  - This is a report of two parent-child families which developed intracranial
      neoplasm. There is no known history of brain tumor in other family members. Two
      instances of familial brain tumors are reported which are different from those
      seen in phakomatosis. Family one had posterior fossa tumors including astrocytoma
      and hemangioblastoma. The second family had endocrine-associated tumors
      consisting of pituitary adenoma and yolk sac tumor.

PMID- 9177090
TI  - Huge calcified chronic subdural hematoma in the elderly--report of a case.
AB  - A 73-year-old man who had a huge calcified chronic subdural hematoma is reported.
      He developed progressive right hemiparesis and conscious disturbance.
      Computerized tomography demonstrated a huge subdural hematoma bordered by a
      calcified rim. A large osteoplastic craniotomy was performed and revealed
      approximately 300 grams of paste-like, muddy blood clot. The calcified outer
      membrane contained proliferating capillaries which was conceivably contributed to
      the leakage of blood. It is noteworthy that an active vascular proliferation was
      observed even in the healed tissue with calcification.

PMID- 9177091
TI  - Presence of very high prevalence and intensity of infection with Fasciola
      hepatica among Aymara children from the Northern Bolivian Altiplano.
AB  - Coprological studies of school children from four communities in the Northern
      Bolivian Altiplano were carried out in order to estimate the prevalences and
      intensities of Fasciola hepatica infection. Single stool specimens were collected
      at random from 558 school children (308 boys and 250 girls) aged 5-19 years old.
      Nineteen different parasite species (13 protozoan and six helminths) were
      detected. Of the children examined, 98.7% (96.5-100%) presented infection with at
      least one parasite species. The mean prevalence of 27.6% by Fasciola hepatica
      (range, 5.9-38.2%) was the highest not only with respect to the helminth species
      found in the Northern Bolivian Altiplano but also among the fasciolosis
      prevalences reported in children in other parts of the world to date. Prevalences
      were significantly different among the communities surveyed and was significantly
      higher in the 9-12 years age group. There were, however, no significant
      differences between sexes. Among the 154 children presenting F. hepatica eggs in
      stools, intensities ranged from 24-5064 eggs per gram of faeces (epg), with
      arithmetic and geometric means of 474 and 201 epg, respectively. Significant
      differences in mean egg output were detected between communities, sexes and age
      groups. Individual fasciolosis infections coexisting with other pathogenic
      parasite species (Entamoeba histolytica and/or E. dispar, Giardia intestinalis,
      Balantidium coli, Dientamoeba fragilis, Cryptosporidium sp., Hymenolepis nana,
      Taenia spp., Trichuris trichiura, Ascaris lumbricoides and Enterobius
      vermicularis) were detected. A significant positive association with F. hepatica
      was only found in the case of G. intestinalis. This coprological study not only
      verifies the existence of high prevalences of F. hepatica among humans in the
      Northern Bolivian Altiplano, but also demonstrates the need to expand the
      Southern boundaries of this high endemic zone to include the Southeastern region
      of Lake Titicaca.

PMID- 9177092
TI  - Distribution and genetic diversity of Schistosoma haematobium within its bulinid
      intermediate hosts in Mali.
AB  - Random amplified polymorphic DNA (RAPD) markers were used to assess distribution
      and genetic diversity of Schistosoma haematobium populations within their bulinid
      intermediate hosts in Mali. Naturally infected snails (Bulinus truncatus and B.
      globosus) were collected at four sites in the Bamako district. S. haematobium
      cercariae from single snails were used to infect mice and genotypes of the
      resultant adult worms were characterized using RAPD markers. Diversity indices
      were calculated at the scale of one snail, both within and among sites. One third
      of the molluscs harboured multiple miracidial infections (the maximum number
      equal to five) with slightly overdispersed distributions in three sites and a
      random distribution at one site. Similarity indices revealed significantly less
      variation among populations compared with populations, indicative of the absence
      of distinct S. haematobium populations within the Bamako district. RAPD markers
      represent an accurate tool for determining genetic diversity and amount of gene
      flow among parasite populations contained within different individual snails and
      among intermediate host populations.

PMID- 9177093
TI  - Schistosoma haematobium induced lesions in the female genital tract in a village
      in Madagascar.
AB  - Female genital schistosomiasis, FGS, was investigated in a gynaecological study
      as part of an overall community based morbidity survey, including parasitological
      and ultrasonographical examination, of a Schistosoma haematobium endemic area in
      Madagascar. Women (103), of childbearing age (15-49 years), were included for a
      gynaecological examination and visible lesions of vagina and cervix were biopsied
      in order to determine the origin of the lesion. Furthermore all women were
      screened for the presence of schistosome ova using PAP smears from the vagina and
      the endo/exo cervix. In total 15 women showed schistosome ova in the vagina
      and/or cervix (median age 24 years and range 15-36 years). Of 36 women with
      cervical abnormalities, 12 eggs were detected by cervical biopsy (33%). In
      addition, two of the 12 presented vaginal induration, which contained eggs. Six
      women had eggs in their PAP smears of which three were egg negative by cervical
      biopsy. The prevalence of positive S. haematobium egg excretion in the urine
      among the 103 women was 69% and the geometric mean egg count of positive
      individuals was 51 eggs/10 ml of urine. Five of the 15 women with confirmed FGS
      had < or = 1 egg/10 ml of urine. Bladder lesions and congestive changes in the
      kidneys were demonstrated by ultrasonographic examination in 33 and 9% of the 103
      women, respectively. None of the 15 women with confirmed FGS had renal
      congestion. Our study demonstrates that FGS is a common manifestation of the
      infection with S. haematobium, even in lightly infected individuals.

PMID- 9177094
TI  - Intraspecific diversity of Schistosoma haematobium in west Africa: chronobiology
      of cercarial emergence.
AB  - Cercarial emergence patterns were used to analyse the intraspecific variability
      within and between nine populations of Schistosoma haematobium collected along a
      transect line from the north to the South of the Ivory Coast (Africa) and using
      Bulinus truncatus or Bulinus globosus as intermediate snail hosts. Statistical
      comparison demonstrated the existence of a chronobiological polymorphism and the
      existence of three homogeneous groups of S. haematobium isolates with mean
      shedding times of the cercariae decreasing from the North to the South. The
      chronobiological variability observed was not correlated with the species of
      Bulinus (B. truncatus vs. B. globosus) implicated in the parasite transmission
      but with the climatic and vegetal features of the transmission area. S.
      haematobium from shaded sites of the forest zone (South) showed cercarial
      emergence patterns significantly earliest than that of S. haematobium from open
      sites of the savanna zone (North). Differences in sensitivity to light intensity
      could characterize the existence of eco-geographical races of S. haematobium one
      of the forest, the other from the savanna.

PMID- 9177095
TI  - Diagnostic evaluation of PCR in goats experimentally infected with Trypanosoma
      vivax.
AB  - Six goats were experimentally infected with a stock of Trypanosoma vivax.
      Parasitaemia was weekly monitored by buffy coat and wet blood film examination
      during a period of 15 weeks and another 3 weeks following drug-treatment. Dried
      blood samples were tested by the polymerase chain reaction (PCR), using an
      extraction method with Chelex 100 (BioRad). PCR proved consistently more
      sensitive than the parasitological techniques.

PMID- 9177096
TI  - Schistosoma japonicum infection in the pig: the effect of a patent primary
      infection on a challenge infection.
AB  - The response of pigs to a challenge infection of Schistosoma japonicum following
      a primary infection was assessed using parasitological parameters and eosinophil
      counts. Twenty-five Danish Landrace/Yorkshire/Duroc crossbred pigs were divided
      into four groups. Group A (n = 10) received a primary infection, group B (n = 5)
      received both a primary and challenge infection, group C (n = 5) received a
      challenge control infection and group D (n = 5) received no infection serving as
      helminth-free controls. A dose of 850 cercariae was administered by intramuscular
      injection at the primary infection (week 0) and challenge infection (week 12).
      The pigs were perfused at week 21, except for half of the group A pigs which were
      slaughtered at week 12. Challenge infection did not result in higher worm burdens
      or tissue egg counts in group B than group A at week 21 and mature/immature worm
      ratios were similar for the two groups. In addition, no increases in faecal egg
      counts or eosinophil counts were observed in group B after challenge infection.
      The results indicate that pigs are able to mount a very rapid and effective
      response to reinfection with S. japonicum following a patent primary infection
      resulting in prevention of establishment of challenge infection schistosomes. An
      anti-worm effect appears to be the main feature of this regulatory host response.

PMID- 9177097
TI  - Regulation of differentiation/maturation in vascular smooth muscle cells by
      hormones and growth factors.
AB  - Smooth muscle cells (SMC) within atherosclerotic lesions show marked alterations
      in their differentiated properties as compared to normal medial SMC. This process
      of de-differentiation of SMC has been referred to as "phenotypic modulation", and
      is characterized by increased growth responsiveness, altered lipid metabolism,
      increased matrix production, and loss of contractile proteins, all of which can
      contribute to the development and/or progression of atherosclerotic disease. As
      such there has been much interest in understanding mechanisms and factors that
      control the differentiation of the vascular SMC. This paper reviews the effects
      of growth factors, growth inhibitors, and other extrinsic factors on
      differentiation/maturation of SMC, with a particular emphasis on consideration of
      factors that may contribute to abnormal control of SMC differentiation in
      vascular disease. In addition, we will briefly summarize what is currently known
      regarding molecular mechanisms that control the coordinate expression of genes
      encoding for SMC-selective/specific proteins that are required for the
      differentiated function of the vascular SMC.

PMID- 9177098
TI  - Novel indices of oxidant stress in cardiovascular disease: specific analysis of
      F2-isoprostanes.
AB  - The development of methods to measure specific isoprostanes affords a unique
      opportunity to investigate both the role of oxidant stress as a mechanism of
      disease in vivo and to select rational doses of putative antioxidant drugs and
      vitamins for evaluation in human disease. The ability to measure these compounds
      directly in situ at the site of their formation, to immunolocalize them to target
      cells in atherosclerotic plaque and other tissues (61) and to assess their
      biosynthesis non-invasively in urine promises to elucidate the role of lipid
      peroxidation in cardiovascular disease.

PMID- 9177099
TI  - Role of thromboxane A2 in mitogenesis of vascular smooth muscle cells.
AB  - Thromboxane A2, a product of activated platelets, is a potent vasoconstrictor and
      promoter of vascular smooth muscle cell growth. Therefore, thromboxane has the
      potential to contribute to processes, such as restenosis following coronary
      angioplasty, characterized by both platelet activation and abnormal vascular
      smooth muscle growth. This article reviews the effects of thromboxane on growth
      of cultured vascular smooth muscle cells, discusses the mechanisms by which
      thromboxane transduces its growth promoting effects in tissue culture with an
      emphasis on the role of endogenously produced basic fibroblast growth factor, and
      reviews clinical studies of thromboxane synthesis inhibitors and/or receptor
      blockers in angioplasty restenosis.

PMID- 9177100
TI  - Roles of vasodilatory prostaglandins in mitogenesis of vascular smooth muscle
      cells.
AB  - Vasodilatory prostaglandins (PGI2, PGE1) and synthetic prostacyclin mimetics
      inhibit smooth muscle cell proliferation in vitro after stimulation by growth
      factors. Similar results are obtained in vivo after endothelial injury,
      suggesting that vasodilatory prostaglandins might also control smooth muscle cell
      proliferation in vivo. However, available data from clinical trials are
      conflicting and currently do not support the concept that these compounds might
      be successfully used to suppress excessive smooth muscle cell growth in response
      to tissue injury, specifically restenosis after PTCA. One possible explanation
      for these different results is an agonist-induced down-regulation of prostacyclin
      receptors in vascular smooth muscle cells. It is possible that enhanced
      endogenous prostacyclin biosynthesis, subsequent to induction of COX-2 and/or in
      relation to the formation of a neointima from media smooth muscle cells, might
      have a similar effect. There is still uncertainty regarding the cellular signal
      transduction pathways and their possibly complex interaction, although cAMP
      dependent reactions are probably involved. In addition, vasodilatory
      prostaglandins might also interfere with the generation and action of other
      growth modulating factors, including PDGF, hepatocyte growth factor and nitric
      oxide. In conclusion, vasodilatory prostaglandins might be considered as growth
      modulating endogenous mediators in vascular smooth muscle cells.

PMID- 9177101
TI  - Antimitotic actions of vasodilatory prostaglandins--clinical aspects.
AB  - A variety of in-vitro antiatherosclerotic actions, among them those on vascular
      smooth muscle cells (mitotic activity, proliferation, extracellular matrix
      production), have been identified especially for PGE1 and PGI2, and proven in
      experimental animals. Ex-vivo data in humans are not yet available. We examined
      the effect of PGE1-, PGI2- and iloprost therapy of various duration (1-4 weeks)
      on smooth muscle cells (mitosis, proliferation, prostaglandin formation from
      exogenous and endogenous substrate) derived from vascular surgery samples. In
      vivo PG-therapy decreases [3H]-thymidine incorporation as well as [35]S- and
      [14C]-proline uptake. These effects are dependent on the duration of treatment,
      PGE1 being trendwise more effective. Arachidonic acid conversion to PGI2 is
      significantly enhanced in activated smooth muscle cells of the plaque, both in
      the intima as well as in the media. Due to the activation of the gene for COX-2,
      the actual synthesis of PGI2 as well as the conversion rate to 6-oxo-PGF1 alpha
      are increased in activated smooth muscle cells, an effect being abolished by the
      PG's administered. It can thus be concluded that PG-therapy for advanced
      atherosclerosis seems to affect vascular smooth muscle cells beneficially,
      decreasing mitotic and proliferative activity as well as collagen and
      glycosaminoglycan synthesis. The somewhat less pronounced effect for PGI2 and
      iloprost could be explained by desensitization at the receptor level as
      preliminary findings suggest. This could become even more relevant if a long-term
      administrable stable (oral) analogue becomes available for routine therapy.

PMID- 9177102
TI  - Prostacyclin and nitric oxide-related gene transfer in preventing arterial
      thrombosis and restenosis.
AB  - Prostacyclin (PGI2) and nitric oxide (NO) are potent vascular mediators, playing
      key roles in protecting arterial wall from injury-induced lesions. The key enzyme
      that catalyzes PGI2 biosynthesis is cyclooxygenase (COX). COX-1 undergoes auto
      inactivation, which severely limits PGI2 synthesis. Overexpression of COX-1 in
      cultured endothelial cells by COX-1 gene transfer was accompanied by a higher
      capacity for and sustained synthesis of PGI2. Adenovirus-mediated COX-1 gene
      transfer to angioplasty damaged carotid arteries in pigs augmented PGI2 synthesis
      and prevents thrombus formation. Transfer of endothelial NO synthase (eNOS) into
      angioplasty injured, carotid arteries was reported to suppress intimal
      hyperplasia in rats. Transfer of PGI2 and NO synthetic enzymes restores the
      vasoprotective properties and represents an exciting new strategy for treating
      arterial thrombotic disorders.

PMID- 9177103
TI  - Changing paradigms and their effect on American Indian and Alaska Native health.

PMID- 9177104
TI  - An epidemiologic review of dietary intake studies among American Indians and
      Alaska Natives: implications for heart disease and cancer risk.
AB  - PURPOSE: Dietary factors play an important role in the occurrence of heart
      disease and cancer. While American Indians and Alaska Natives (AIANs) have unique
      heart disease and cancer mortality profiles, little is known about the effect of
      diet on heart disease and cancer risk in these populations. This paper reviews
      existing nutritional intake data from adult AIANs, and considers the potential
      impact of diet on heart disease and cancer in these communities. METHODS: A
      review of the literature was conducted using the Medline database system and
      other reference materials. Studies documenting nutrient intakes only were
      included in this review. Studies were limited to those among healthy, non
      pregnant adults. RESULTS: A total of twelve reports from 1959 to 1996 were found.
      Sample sizes for the studies ranged from 20 to 575 subjects. Most studies were
      done among women, and a variety of nutritional assessment techniques (24 hour
      recall, food frequency questionnaire, multiple-day food record) were used. Most
      studies also had limited nutrient intake data, especially for dietary fiber and
      vitamin E. The majority of studies reported moderately high intakes of fat and
      saturated fat, and low intakes of polyunsaturated fat and fiber. CONCLUSIONS:
      Based on the limited data, diet may play an important role in the heterogeneity
      of heart disease and cancer mortality in AIAN communities. More research is
      needed to assess the impact of diet on heart disease and cancer risk, including
      more longitudinal data, and data to assess the validity and reliability of
      traditional methods of dietary assessment.

PMID- 9177106
TI  - Can econometrics rescue epidemiology?

PMID- 9177105
TI  - Epidemiology of alcohol use in a group of older American Indians.
AB  - PURPOSE: This study describes alcohol use in a group of older American Indians
      and the associations with demographic and health status characteristics, by
      gender. METHODS: Alcohol use was examined in a cross-sectional, population-based
      study of 161 American Indians, aged 45-76 years (a substudy of the Strong Heart
      Study). Alcohol use was measured by a questionnaire administered during a
      personal interview. Information about demographic characteristics and health
      status was ascertained from interviews and abstraction of medical records.
      RESULTS: A higher proportion of men than women had used alcohol heavily (71% vs.
      28%). Men were more likely than women to drink currently (46% vs. 18%), to binge
      (26% vs. 5%), and to screen positive for alcoholism (77% vs. 43%). Among current
      drinkers, > 30% had diabetes, and the average score on the Short Michigan
      Alcoholism Screening Test (SMAST) was in the alcoholic range. Heavy drinking was
      associated with more symptoms of depression in women (P < 0.05) and fewer in men
      (P < 0.05). Alcoholism was positively associated with a history of heavy drinking
      in both men (P < 0.05) and women (P < 0.001). CONCLUSIONS: Alcohol use was common
      and varied by gender. Alcohol use also varied according to other sociodemographic
      and health status characteristics. Since many older American Indians with chronic
      illness are currently drinking, this age group may require enhanced alcohol
      control programs.

PMID- 9177107
TI  - Econometric approaches to epidemiologic data: relating endogeneity and unobserved
      heterogeneity to confounding.
AB  - The concepts of endogeneity and unobserved heterogeneity are well-known among
      econometricians. However, these issues are rarely addressed in epidemiologic
      studies. This paper explores these two concepts, their relationship to each
      other, and the implications for analysis in epidemiologic studies. An endogenous
      variable is defined as a predictor variable which is partly determined by factors
      within the model itself, while unobserved heterogeneity is conceptualized as a
      vector of missing variables acting through the error term. Under certain
      assumptions, the simultaneous existence of an endogenous variable and unobserved
      heterogeneity is shown to act in a manner analogous to confounding. Specifically,
      this occurs due to an association between the error term in the equation and the
      endogenous predictor variable. The accepted econometric solution to this problem
      is to replace the endogenous variable with an 'instrumental variable' which is
      not correlated with the error term and thus not susceptible to confounding. The
      validity of these concepts and of the proposed solution are discussed.

PMID- 9177108
TI  - Dies endogeneity matter? A comparison of empirical analyses with and without
      control for endogeneity.
AB  - PURPOSE: Using data from the Cebu Longitudinal Health and Nutrition Survey, we
      perform an empirical investigation of the effects of endogeneity and unobserved
      heterogeneity in the analysis of health outcomes. METHODS: First, we lay a
      theoretical background for this analysis and develop a set of expectations
      regarding the effects of ignoring endogeneity. Then, by modeling the effect of
      infant-feeding patterns on time to resumption of menses, we perform parallel
      analyses with and without control for endogeneity. RESULTS: We show that in this
      analysis, as far as the effects of endogeneity are concerned, empirical results
      do accord with theoretical expectations. There are differences in parameter
      estimates between models, that lead to somewhat different interpretations.
      CONCLUSIONS: We discuss the importance and implications of these findings for
      epidemiological studies of health outcomes. We outline the steps involved in such
      an analysis and discuss the practical limitations of the methods, as well as the
      possible gains.

PMID- 9177109
TI  - Epidemiologic determinants of endometriosis: a hospital-based case-control study.
AB  - PURPOSE: Risk factors for endometriosis were identified through data obtained
      from a case-control study at Brigham and Women's Hospital in Boston,
      Massachusetts. METHODS: Cases were 50 women with infertility-associated
      endometriosis. The primary control group consisted of 89 fertile women without
      endometriosis, and an alternate control group consisted of 47 infertile women
      without endometriosis. RESULTS: The risk of endometriosis was positively
      associated with height (OR), 2.8 per 10 cam increase; 95% confidence interval
      (CI), 1.4-5.6) and inversely associated with weight (OR, 0.7 per 10 kg increase;
      95% CI, 0.5-1.0) and body mass index (OR, 0.7 per 5 kg/m2 increase; 95% CI, 0.4
      1.1). We observed an inverse association with exercise (OR, 0.6; 95% CI, 0.3
      1.5), but the effect was limited to women who exercised > or = 4 hours per week
      (OR, 0.4; 95% CI, 0.2-1.2). Endometriosis was not associated with either smoking
      or alcohol consumption. CONCLUSIONS: Our findings suggest that the fertility
      status of controls can strongly influence associations seen with menstrual
      characteristics. This study is one of few to address the issue of control
      selection for a case-control study of endometriosis. Specifically, potential
      problems encountered using fertile and infertile control women are examined and
      discussed.

PMID- 9177110
TI  - Parenthood and lipid and lipoprotein levels in older men.
AB  - PURPOSE: Parenthood for men and women has been associated with longevity, good
      physical health, and a deterrent effect on negative health behaviors which may
      affect subsequent mortality. However, decreased high density lipoprotein
      cholesterol (HDL-C) levels have been reported in women with greater numbers of
      pregnancies. Similar studies have not been reported in men. The present study
      examines the association of number of biological and nonbiological children with
      lipid and lipoprotein levels in men. METHODS: Subjects included 1039 community
      dwelling men aged 50-89 years. A standardized interview was used to obtain
      information on numbers of biological, adopted and stepchildren. Fasting total
      HDL, LDL cholesterol, and triglycerides were measured. RESULTS: Men with five or
      more biological children were more obese than men without biological children.
      Alcohol consumption, cigarette smoking, and exercise did not vary in relation to
      the number of biological children. Only triglyceride levels were higher in men
      with four, five, or more children, and lower in men with one child as compared to
      men with no children, but this difference was no longer statistically significant
      after adjustment for obesity. CONCLUSIONS: These results show no favorable effect
      of parenthood for men with regard to lifestyle, lipid, or lipoprotein levels.
      Increased triglyceride levels in men with more children appeared to be mediated
      by greater obesity in men with five or more biological children. These data also
      suggest that relations between parity and HDL-C levels found for women, could be
      associated with either the long term biologic consequences of pregnancy or the
      stress of childrearing.

PMID- 9177111
TI  - Green tea intake in relation to serum lipid levels in Middle-aged Japanese men
      and women.
AB  - PURPOSE: The relationship between green tea intake and serum concentrations of
      total cholesterol, triglycerides, and high density lipoprotein cholesterol was
      examined. METHODS: The subjects were 630 middle-aged men and their 370 wives
      sampled from five regions of Japan during 1989-1991. Consumption frequency of 38
      foods, including green tea, was determined by interview. Three-day food records
      were collected from 207 of the men and 164 of the wives. The mean serum
      concentrations of the three lipids were compared according to the three levels of
      daily green tea intake (< 1 cup, 1-4 cups, and > 4 cups), with adjustments for
      various health habits, food frequencies, and nutrient intakes. RESULTS: After
      extensive multivariate adjustments for nondietary and dietary covariates, green
      tea was not associated with any of the lipid levels. CONCLUSIONS: The results of
      this cross-sectional study do not support the beneficial effects of green tea on
      serum lipid levels.

PMID- 9177112
TI  - Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged
      adults.
AB  - PURPOSE: Many epidemiologic studies have identified elevated plasma
      homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease.
      To examined the relationship between vitamin intakes and plasma homocyst(e)ine,
      we analyzed dietary intake data from a case-control study of 322 middle-aged
      individuals with atherosclerosis in the carotid artery and 318 control subjects
      without evidence of this disease. METHODS: All of these individuals were selected
      from a probability sample of 15,800 men and women who participated in the
      Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: Plasma homocyst(e)ine
      was inversely associated with intakes of folate, vitamin B6, and vitamin B12
      (controls only for this vitamin)--the three key vitamins in homocyst(e)ine
      metabolism. Among nonusers of vitamin supplement products, on average each
      tertile increase in intake of these vitamins was associated with 0.4 to 0.7
      mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma
      homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and
      iron. Methionine and protein intake did not show any significant association with
      plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls
      showed similar associations between dietary variables and plasma homocyst(e)ine.
      Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L
      lower than that among nonusers. Further studies to examine possible causal
      relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular
      disease are needed.

PMID- 9177113
TI  - Gastric cancer in the European Union (1968-1992): mortality trends and cohort
      effect.
AB  - PURPOSE: To analyze patterns and trends in gastric cancer mortality in the
      European Union (EU) over the period 1968-1992, paying special attention to
      changes associated with birth cohort. METHODS: Poisson log-linear models were
      used to quantify geographic differences and relative annual changes. To assess
      trends associated with birth cohort, invariant parameters from sex-specific age
      period-chohort models (net drift and curvature), for each country, were used to
      choose a restricted slope range for cohort effect. RESULTS: Gastric cancer
      mortality declined throughout the EU. The male-to-female ratio stood at around 2
      in all countries, yet showed a slight rise over time. Portugal reported the
      highest age-adjusted rates for men and women (45.63 and 23.31 per 100,000 person
      years, respectively). The rate ratio between two extreme countries
      (Portugal/Denmark) exceeded 3. Quantitative intercountry differences were found
      in trend slopes, with a decrease of 5% per annum in Finland. Risk of dying
      associated with birth cohort decreased over successive generations. Small local
      rises in risk, in almost all countries among generations born around the 1940s,
      support the importance of diet early in life in the etiology of gastric cancer.
      CONCLUSIONS: Despite the substantial decline in gastric cancer mortality
      witnessed in the EU, stress must be accounted for the wide differences among
      countries and the smaller decline in the youngest generations, particularly among
      women. This latter finding suggests a possible stabilization or even a rise in
      the rates in future, rendering it important for these trends to be monitored over
      the next few years.

PMID- 9177114
TI  - Recruitment of minority students to U.S. epidemiology degree programs. The
      American College of Epidemiology Committee on Minority Affairs.
AB  - PURPOSE: African-, Hispanic-, and Native Americans are underrepresented in the
      field of epidemiology including degree programs. As part of the assessment
      component of its mandate, the American College of Epidemiology Committee on
      Minority Affairs conducted a survey of minority recruitment activities of U.S.
      epidemiology degree programs. METHODS: The survey, containing questions related
      to marketing activities, institution infrastructure, financial support, academic
      offerings, and receptive/supportive environment, was mailed to all programs
      identified in Episource as offering epidemiology degrees. Separate responses were
      requested concerning activities at the department and school levels. RESULTS:
      Fifty-two completed questionnaires were received (response rate of 79%). All but
      two institutions had at least one activity conducted by either the department or
      the school. However, all activities were more common at the school- than at the
      department-level. Indeed, some activities [a written minority student recruitment
      plan (6% of departments and 52% of schools), personnel with minority recruitment
      responsibilities (4% of departments and 73% of schools)] were almost exclusively
      school-sponsored. Although marketing-type activities were the most common
      minority recruitment tool used by departments, only 21% made visits to minority
      schools, 17% visited other colleges specifically to recruit minorities, and 12%
      produced materials targeted to ethnic/racial minorities. Six percent of the
      departments and 19% of the schools offered financial support (grants,
      fellowships, scholarships) to almost all underrepresented minority students.
      CONCLUSIONS: Even though individual epidemiology degree programs may not see a
      need for general recruitment activities in order to maintain the size of their
      applicant pool, minority-specific recruitment activities should be undertaken to
      enhance and diversify that pool. We recommend that epidemiology departments
      develop, adopt, and implement comprehensive written plans for the recruitment of
      underrepresented minority students into their programs.

PMID- 9177115
TI  - Obesity, alcohol consumption, smoking, and mortality.
AB  - PURPOSE: The goals of this study were to assess prospectively the impact of
      obesity, alcohol use, and smoking on total mortality and to test the etiologic
      hypothesis that subjects with two or more of these risk factors may experience an
      elevated risk of overall mortality. METHODS: Information on body mass index
      (BMI), alcohol intake, cigarette smoking, and other life-style factors was
      obtained from a cohort of 8006 Japanese-American men living in Hawaii. They were
      between 45 and 68 years of age at the initial examination (1965-1968). After 22
      years of follow-up that included nearly 159,000 person-years of observation, 2667
      deaths from all causes were identified. RESULTS: There was a significant
      quadratic (J-shaped) relation between BMI and overall mortality. A weaker J
      shaped pattern in risk was also present for the intake of alcohol. A strong
      positive association was observed with pack-years of cigarette smoking. A
      synergistic interaction between BMI and alcohol was statistically significant (P
      = 0.0017). Specifically, men who had the lowest body mass (BMI < 21.21 kg/m2) and
      drank moderately to heavily (> or = 25 oz/mo) experienced a 63% excess risk
      (relative risk, 1.63; 95% confidence interval; 1.33 - 1.99) compared to a
      reference group composed of men who had intermediate body mass (BMI, 21.21 -
      26.30 kg/m2) and drank occasionally to lightly (0.01 - 24.99 oz/mo). The increase
      in risk due to the interactive effect of low BMI and high alcohol intake was
      stronger (and statistically significant) than when each of these risk factors was
      considered separately (excess risk, 28% and 2%, respectively). There was no
      significant interaction for BMI and cigarette smoking, for alcohol and cigarette
      smoking, or for the three factors combined. CONCLUSIONS: The most important
      finding of this study was that, in addition to confirming that cigarette smoking
      could shorten life, extreme (high or low) BMI values and high alcohol consumption
      are each potentially harmful to health, but even more so if moderate or heavy
      drinking is concomitant with low body mass, a possible indicator for low intake
      of nutrients.

PMID- 9177116
TI  - Influence of pepsinogen gene polymorphisms on serum pepsinogen.
AB  - We identified pepsinogen C (PGC) gene polymorphisms by means of PCR, which
      amplified DNA in the region within the intron between exons 7 and 8, and by 6%
      polyacrylamide gel electrophoresis. Six alleles were found in a Japanese
      population. The frequencies of these alleles in 408 unrelated Japanese
      individuals were 0.074, 0.026, 0.335, 0.237, 0.016 and 0.314, respectively. The
      serum pepsinogen II level significantly decreased in the order of the allele 6
      homozygote, the allele 6 heterozygote and the other genotypes (chi 2 = 7.850,
      D.F. = 2, p = 0.020). These findings indicated that the genetic background of
      serum pepsinogen should be considered when screening for stomach cancer by this
      procedure.

PMID- 9177117
TI  - Molecular and cytological investigations of phosphoglucomutase (PGM1) in the K562
      cell line.
AB  - Phosphoglucomutase 1 (PGM1) deficiency is a stable characteristic of the
      erythroleukaemic cell line, K562, whereas the activity of the isozymes of the
      other two PGM loci (PGM2 and PGM3) is slightly elevated. In this study the
      molecular basis of PGM1 deficiency was investigated by a combined approach
      utilising protein electrophoresis, immunodetection, cytogenetic techniques, and
      DNA and RNA analysis. Isoelectric focusing and activity staining confirmed that
      K562 has no detectable PGM1 activity. Immunoblot analysis of extracts, separated
      by isoelectric focusing, starch gel and SDS gel electrophoresis, using
      monospecific anti-PGM1 antibodies showed that K562 contained no detectable
      immunoreactive material. Karyotype analysis revealed the presence of two intact
      chromosomes 1 and a derivative chromosome 1, der(1)t(1;11), each of which carried
      a copy of the PGM1 gene as demonstrated by fluorescence in situ hybridization
      using a PGM1 cosmid as probe. Southern blot analysis using a PGM1 cDNA clone as
      probe suggested that the PGM1 genes had not been subject to any gross structural
      rearrangements. We were also able to determine that K562 is type PGM1 2+1+ by
      restriction endonuclease analysis of genomic DNA. Very low levels of PGM1 mRNA
      which appeared to be full length transcripts were detected in K562 using a
      reverse transcriptase PCR technique. We conclude that the most likely cause of
      PGM1 enzyme deficiency in K562 is abnormal regulation of transcription.

PMID- 9177118
TI  - A two-locus model for hereditary non-polyposis colorectal cancer in Modena,
      Italy.
AB  - Complex segregation analysis was conducted in a series of patients with
      hereditary non-polyposis colorectal cancer (HNPCC) ascertained through probands
      registered in the Cancer Registry of the Health Care District of Modena, Northern
      Italy. Altogether there were 125 nuclear families segregating for HNPCC, for a
      total of 672 individuals. The analysis favoured a two-locus model, with both
      susceptibility genes rare and dominant. The gene frequency of the deleterious
      allele at the major locus is estimated to be low qm = 0.004 and for the second
      locus the estimate is even lower q = 0.00003. Both genes defining the two-locus
      model seem to be highly penetrant. The lifetime penetrance of the abnormal gene
      at the major locus is estimated to be 0.73 for female, while the estimation for
      male is higher, 0.85.

PMID- 9177119
TI  - A biometrical study of the relationship between sodium-lithium countertransport
      and triglycerides.
AB  - We addressed the question: Is there evidence that allelic variation in a single
      unmeasured gene that has a large effect on maximal activity of erythrocyte sodium
      lithium countertransport (Na-Li CNT) also has pleiotropic effects on variation in
      plasma triglyceride levels? Complex segregation analysis models that included
      plasma triglyceride levels as a covariate were considered as explanations for
      interindividual variation in Na-Li CNT. A sample of 711 healthy adults from 254
      pedigrees enrolled in the Rochester Family Heart Study was selected for this
      study. The majority of the pedigrees supported the hypothesis that variations in
      a single unmeasured non-transmitted environmental factor have large effects on
      the Na-Li CNT distribution. Only gender-specific first-order covariate parameters
      were necessary in the complex segregation models suggesting that the form of the
      relationship between Na-Li CNT and plasma triglyceride level was not influenced
      by variation in the inferred environmental factor with large effects.
      Stratification of the sample by this inferred environmental factor resulted in
      three classes of individuals with significant differences in the distributions of
      coronary heart disease risk factor traits, as well as interindividual variation
      in both Na-Li CNT and plasma triglyceride levels. These results, along with other
      observations from the Rochester Family Heart Study sample, emphasize the complex
      and multifactorial nature of the causes of interindividual variation in Na-Li
      CNT. Our study further suggests that new research strategies are needed for
      studying the relationships between genetic and environmental variation and
      variation in quantitative traits such as Na-Li CNT that have been identified as
      risk factors for hypertension.

PMID- 9177121
TI  - The comparative role of consanguinity in infant and childhood mortality in
      Pakistan.
AB  - As part of the 1990/1991 Pakistan Demographic and Health Survey, data were
      collected on the outcome of 26,408 births to 6,611 women, with mortality rates
      investigated at specific age intervals during the first 5 years of life.
      Bivariate and multivariate logistic regression analyses were employed to examine
      the comparative roles of consanguineous marriage and a number of demographic and
      socioeconomic factors, including the sex of the child, maternal age, maternal
      education, birth interval and birth order, as determinants of early death. The
      results indicate that, even after controlling for these non-genetic variables,
      inbreeding at the level of first cousin exerted a significant adverse effect on
      survival in four of the five age intervals examined, neonatal, post-neonatal,
      infant and under 5 years.

PMID- 9177120
TI  - Heterogeneous effects of natural selection on the Italian newborns.
AB  - We have studied the impact of natural selection through stillbirth on the Italian
      population, taking into account the socio-economic heterogeneity of the country.
      The results suggest that older age at delivery and lower cultural level of the
      mothers, indicators of critical biological and socio-economic conditions, even at
      present increase stillbirth risk. Moreover, in the less favourable environment of
      the southern regions, selection is still sex-specific.

PMID- 9177122
TI  - On extending the transmission/disequilibrium test (TDT).
AB  - The transmission/disequilibrium test (TDT), for evaluation of the null hypothesis
      of neither linkage nor association between a marker locus and disease, is
      extended to the more general situation of transmission of two multi-allele marker
      loci from parents to affected offspring. Transmission probabilities are derived
      for a generalized single locus disease model, where the disease locus is taken to
      lie between the two marker loci. There could be unlinked modifier loci for the
      disease. Examples of the extended TDT are given and it is shown how the
      contribution from each locus can be evaluated, both separately and jointly.

PMID- 9177123
TI  - Testing a genetic equilibrium across strata.
AB  - A score statistic for testing the Hardy-Weinberg law for data sampled from
      several populations with different allele frequencies is derived assuming a
      common coefficient of disequilibrium (odds ratio-type) across strata. The
      assumption can be examined by a chi-square goodness-of-fit test. It is unlikely
      such a model would be rejected in typical studies involving human populations.
      Under this model, a Wald-type test has substantially less power than the score
      test. An approximate formula for the sample size required for a specific power of
      the stratified score test for detecting departure from equilibrium is given.

PMID- 9177124
TI  - Secondary vestibular projection to the reticular formation of rabbit lower
      brainstem with reference to reciprocity.
AB  - The secondary vestibular projection to the RF of lower brainstem was studied in
      the rabbit by retrograde transport of HRP and WGA-HRP. The projection is rather
      strong and originates bilaterally in all the main vestibular nuclei. The majority
      of afferents to the RF arise in the ventrolateral and ventromedial regions of MV
      and IV, respectively, whereas projections from SV and the ventral region of LV
      are weaker. Although no clear-cut topographical relationship was noted between
      location of neurons in the VNC and projection sites in the RF, some degree of
      preferential connections was found. All four vestibular nuclei project to RGc,
      though SV and LV contribute less than the others. Rpc alpha is supplied by fibers
      from MV and IV. RPc and Rpc receive projections from MV and/or IV. A minute
      connection was traced from the interstitial nucleus of the VIII nerve to RGc. The
      RF nuclei relaying vestibular information may plan an important role in the
      control of eye and head movements as well as in the postural adjustments required
      during animal displacement. The present results are discussed in comparison with
      those of earlier studies and with reference to reciprocity.

PMID- 9177125
TI  - The effect of optokinetic stimulation on daytime sleepiness.
AB  - This study examined the effect of optokinetic stimulation on objective
      sleepiness, as measured by the Multiple Sleep Latency Test (MSLT). The Nightcap,
      a portable sleep monitor, was used in a novel way to perform MSLTs, as well as
      record sleep in the home. Subjects wore the Nightcap for seven consecutive
      nights. On days 3 and 5 of the protocol, subjects came into the lab for an MSLT.
      On the experimental day, subjects underwent 10 minutes optokinetic stimulation
      (OKS), resulting in moderate motion sickness prior to each MSLT trial. Although
      subjects in the OKS condition reported significantly more drowsiness than
      controls, this did not result in significantly reduced sleep latencies.

PMID- 9177126
TI  - Changes in tension-frequency relationship of motor units induced by their
      activity in rat muscle.
AB  - In 57 motor units of rats' medial gastrocnemius muscle the influence of activity
      on the course of 10 successively repeated tension-frequency curves (T-f curves)
      was observed. In slow motor units the steep parts of successive T-f curves
      usually shifted slightly towards higher frequencies. However, in some slow units
      of relatively short contraction these T-f curves shifted towards lower
      frequencies. In fast units, especially those of the FF type, more marked changes
      were observed in T-f curves. At first, a shift of the second to third curve
      towards lower frequencies was observed. Curves then shifted progressively towards
      higher frequencies. In all motor units greater changes in tension could be
      observed in unfused tetani than in fused tetani. In some motor units the tension
      of fused tetani showed a progressive decrease. Changes in the course of T-f
      curves related to changes in contraction and relaxation times. The results
      presented here explain how the duration of the activity can change the
      sensitivity of motor unit tension to the frequency of stimuli. The importance of
      the changes observed in the T-f relation in the process of fatigue is discussed.

PMID- 9177127
TI  - The role of tonic vestibular input for postural control in rats.
AB  - Removal of a vestibular organ deprives the ipsilateral vestibular nuclei of tonic
      excitatory inflow from vestibular afferents, and thus evokes a central asymmetry,
      that is imbalance between tonic activity of the left and right vestibular nuclear
      complexes. In the present study, the effect of the central asymmetry upon a
      function of different motor systems was investigated in the freely behaving rats
      subjected to unilateral or bilateral labyrinthectomy (UL or BL). In four sets of
      experiments the following results have been obtained. 1. Seven UL-evoked symptoms
      (which reflect impairment of different motor systems) were qualitatively
      characterized. The short-lasting symptoms were: (1) body twisting, (2) rolling,
      (3, 4) extension of the fore- and hindlimb contralateral to UL, and (5) circling.
      These symptoms disappeared in a fixed order during recovery from anesthesia.
      During of expression of the symptoms was very short (< 1 hour) with the Halothan
      anesthesia and much longer (approximately 8 hours) with the chloral hydrate
      anesthesia. The long-lasting symptoms were (6) spontaneous ocular nystagmus, that
      persisted for 3 days after UL, and (7) head roll tilt, that persisted for at
      least several weeks after UL. 2. In BL-animals, stimulation of one of the 8th
      nerves was performed (by means of an implanted electrode; pulses 0.3 ms, 50 Hz,
      current up to 400 microA). By increasing gradually the strength of the
      stimulating current, we could evoke all the UL-symptoms but generally in the
      order (7-->1) which was the reverse as compared to the order of disappearance of
      the corresponding symptoms during recovery after UL (1-->7). These findings
      suggest that different symptoms need different levels of the central asymmetry
      for their appearance, and these levels also determine the order of disappearance
      of the symptoms during recovery from UL. 3. In UL-animals, by stimulating the 8th
      nerve on UL-side with a properly adjusted current (200-400 microA) we could
      immediately abolish all the symptoms except (6), which was, however, considerably
      reduced. This finding suggests that stimulation of the 8th nerve in UL-rats
      restores the central symmetry, which results in a concerted disappearance of
      almost all symptoms. In addition to the intermediate effects, stimulation of the
      8th nerve in UL-animals resulted in a long-lasting effect, that is a reduction of
      the head roll tilt which persisted for at least 10 days after stimulation. 4. In
      BL-animals bilateral stimulation of the 8th nerve resulted in restoration of the
      muscular tone, and in considerable improvement of the control of the head
      position.

PMID- 9177128
TI  - Metabolic properties of the sensory neurons in the rat dorsal root ganglion.
AB  - The dorsal root ganglion (DRG) neurons were classified in the rat on the basis of
      their metabolic enzyme properties as determined by quantitative analysis in
      histochemical staining. In particular, nicotinamide adenine dinucleotide
      diaphorase (NADH-d) and alpha-glycerophosphate dehydrogenase (alpha-GPD)
      activities were examined on two serial sections from the same neurons in the
      lumbar (L4) DRG. The DRG neurons were classified into three groups based on the
      soma diameter distribution; small, intermediate and large size DRG neurons. The
      NADH-d activity showed a unimodal distribution in all size groups, while the
      alpha-GPD activity clearly showed a bimodal distribution in the intermediate and
      large size neurons, but not in the small size neurons.

PMID- 9177129
TI  - Discharge of cutaneous afferent fibers innervating tail during passive tail
      movements in cats.
AB  - The discharge of cutaneous afferents innervating the tail were recorded from 145
      single afferent fibers in 11 spinalized cats (conduction velocity: 32-58 m/s)
      during sinusoidal tail movements. Cutaneous afferent fibers were roughly
      classified into two groups, slowly-adapting (SA) and rapidly-adapting fibers
      (RA). The discharge patterns of afferent fibers during passive tail movements
      depended on the receptive field on tail skin. The results of the present
      experiments show that peripheral inputs from cutaneous afferent fibers sent
      various information regarding tail movement and position to central nervous
      systems.

PMID- 9177130
TI  - Introduction to the neurophysiological study of sleep: central regulation of
      skeletal and ocular activities.
AB  - This paper investigates the historical evolution of the major experimental
      results in the field of the central mechanisms underlying the skeletal motor
      activities and the eye movements during sleep. First, the neurophysiological
      background of paradoxical sleep atonia and paradoxical sleep without atonia was
      examined. Then, the analysis was directed to the eye movements in humans and
      animals, their central command processes and their correlative
      electrophysiological activities: ponto-geniculo-occipital waves and eye movement
      potentials.

PMID- 9177131
TI  - Pattern of recovery of species-specific cuticular hydrocarbon mixtures by
      Reticulitermes santonensis and Reticulitermes lucifugus grassei after being
      removed from a mixed group. Is the acquisition of allospecific hydrocarbons
      reversible?
AB  - Each of the termite species Reticulitermes santonensis and Reticulitermes
      lucifugus grassei has its own particular cuticular chemical profile. When members
      of the two species are placed together to form artificially mixed species groups,
      their chemical profiles undergo changes: Each species acquires all the
      hydrocarbons which initially characterized the other species. When the members of
      a mixed group which had been kept together for 24 h were slit into two
      homospecific groups, the cuticular profiles of the members of both groups
      immediately showed a sharp drop in both the homospecific and allospecific
      components. In R. santonensis, the homospecific hydrocarbons subsequently
      increased in quantity, reaching values which were higher on the 33rd day after
      the separation than those initially recorded in this species; whereas in R.
      lucifugus grassei, the homospecific hydrocarbon proportions were still lower on
      the 33rd day than the initial values. In both species, the allospecific
      hydrocarbon levels began to increase sharply on the 5th day after separation, and
      the homospecific products still showed no tendency to return to the initial
      proportions 33 days after separation. In the light of these results, some
      hypotheses are put forward as to what mechanisms might possibly regulate the
      hydrocarbon profiles of these two species.

PMID- 9177132
TI  - Purification and characterization of juvenile hormone esterase from hemolymph of
      the Colorado potato beetle.
AB  - In the Colorado potato beetle (Leptinotarsa decemlineata), low juvenile hormone
      (JH) titers are necessary to initiate metamorphosis and diapause. Low JH titers
      coincide with high activities of JH esterase, which occur mainly in the
      hemolymph. The specific activity of JH esterase appeared to be highest in the
      last larval instar, at day 3 after the molt, and reached a value of 13.5
      nmol/min/mg. JH esterase was purified from hemolymph collected at this stage be a
      sequence of separation systems, including preparative nondenaturing PAGE,
      isoelectric focusing, and SDS-PAGE. The enzyme had a molecular weight of 120,000
      and was composed of two subunits with molecular weights of 57,000, which were not
      linked by disulphide bridges. Isoelectric focusing revealed two forms of the
      enzyme with isoelectric points of 5.5 and 5.6. The Km and kcat of the purified
      enzyme were determined. The major form with pl 5.6 had a Km of 1.4 x 10(-6) M and
      a kcat of 0.9 s-1 and the minor form with pl 5.5 had a Km of 2.2 x 10(-6) M and a
      kcat of 1.9 s-1. The quaternary structure of L. decemlineata JH esterases, as
      differs from JH esterases in other species, which are monomers.

PMID- 9177133
TI  - Endogenous ecdysteroid levels and rates of ecdysone acylation by intact ovaries
      in vitro in relation to ovarian development in adult female crickets, Acheta
      domesticus.
AB  - Ecdysteroid titres have been determined in adult female house crickets (Acheta
      domesticus) in relation to reproductive maturation. Ecdysteroid levels in newly
      emerged adult females are low except in the gut and carcass, which probably
      reflects the remnants of the preecdysial ecdysteroid peak. Ecdysteroid levels in
      all compartments increase markedly once ovarian weight surpasses 10 mg. Apolar
      ecdysteroid conjugates (ecdysone 22-fatty acyl esters) predominate in ovarian
      tissue throughout ovarian maturation, but low levels of free ecdysteroid and
      polar conjugated ecdysteroids are also present. During this period, two peaks of
      ecdysteroids (mainly free and apolar conjugated ecdysteroids) are observed in the
      haemolymph, gut, and carcass compartments. The peaks in the haemolymph occur when
      the ovarian mass reaches 30 and 100 mg. The gut and carcass may be acting as
      sinks or sites of metabolism for the hormone released from the ovaries. The rate
      of ecdysone acylation by ovaries was found to be developmentally regulated,
      increasing from low levels in the immature ovaries of newly emerged females as
      the ovaries increase in size. A semiquantitative assay has been developed to
      identify compounds which inhibit the conversion of [3H]ecdysone into 22-fatty
      acyl [3H]ecdysone by ovaries in vitro. A number of ecdysteroids possessing a free
      hydroxyl group as C-22 as well as the side-chain stereochemistry of ecdysone
      effectively inhibit this conversion, probably by acting as competitive
      substrates. In the cases of 20-hydroxyecdysone and ponasterone A, it was clearly
      demonstrated that these compounds are converted to a mixture of C-22 fatty acyl
      esters. Several other compounds which have been suggested to affect ecdysteroid
      metabolism/mode of action in other systems were also tested for their effects on
      the acyltransferase activity of ovaries in vitro.

PMID- 9177134
TI  - Lipophorin density variation during oogenesis on Rhodnius prolixus.
AB  - The density of lipophorin was determined in adult females of Rhodnius prolixus on
      different days after a meal. Several populations od lipoproteins, differing in
      density but always in the range of HDL, were found in the hemolymph. The density
      of the major population was analyzed and a complex profile of density variation
      was found associated with the principal metabolic events in these insects
      digestion and oogenesis. During the initial three days after the blood meal, with
      the onset of the digestive process, the density of lipophorin decreased from
      1.1185 g/l to 1.1095 g/l, associated with the transfer of lipids from midgut to
      the lipophorin particles. During the period of intense vitellogenesis and lipid
      uptake by the ovary, the lipophorin density started to increase and reached the
      value, 1.1322 g/l, and remained stable up to the end of oogenesis. As soon as the
      requirement of lipids to build up the oocytes ceased, the density of lipophorin
      decreased to its initial value associated with the transfer of lipids from fat
      body to lipophorin. Soon after the blood meal the midgut was the main source of
      lipids capable of replenishing the lipophorin particles, while the fat body
      assumed this function during the succeeding days and reached its maximum capacity
      around day 10, as estimated by the rate of lipid transfer. The principal lipids
      transferred were phospholipids and diacylglycerols. Except in the protein/lipid
      ratio no major changes were observed among different lipids isolated from
      lipophorin of different densities.

PMID- 9177135
TI  - Structure-activity relationships in C-terminal fragment analogs of pheromone
      biosynthesis activating neuropeptide in Helicoverpa zea.
AB  - A number of analogs of the C-terminal hexapeptide of PBAN were prepared and
      tested in vivo for pheromonotropic activity in Helicoverpa zea. Peptides prepared
      with longer-chain omega-aminocarboxylic acids (Tyr-6-aminocaproyl-Leu-NH2 and Tyr
      7-aminoheptanoyl-NH2) were active at 25 and 2.5 nmol. Acetyl-Pro-Arg-Leu-NH2 was
      active at 1,000 pmol and represents a new minimum active fragment in the PBAN
      system. Addition of a bulky, hydrophobic tail (4-octylphenoxyacetyl) to the C
      terminal hexapeptide of PBAN gave an analog that was active at all concentrations
      tested from 1 to 1,000 pmol when injected, had slight oral activity, but had no
      activity when applied topically. Glu-Tyr-Phe-Ser-Pro-Arg-Leu-NH2 was active at
      1,000 but not at 100 pmol; at the latter dose it synergised the activity of 5
      pmol of PBAN.

PMID- 9177136
TI  - Evaluation of hyperactivity produced by pyrethroid treatment on third instar
      nymphs of Triatoma infestans (Hemiptera:Reduviidae).
AB  - The hyperactivity produced in third instar nymphs of Triatoma infestans by their
      exposure to films of deltamethrin or cis-permethrin was evaluated. Both
      pyrethroids produced a significant increase in locomotor activity at 26 and 36
      degrees C but not at 16 degrees C. At 26 degrees C, only deltamethrin produced
      hyperactivity when topically applied on the dorsal side of the nymph's abdomen.
      However, both pyrethroids produced hyperactivity when topically applied on the
      head of the nymphs. Hyperactivity was not observed when nymphs were treated with
      N-ethylmaleimide (20 micrograms/insect) before exposure to the pyrethroids. The
      effect of both insecticides on locomotor activity reversed the inhibitory
      influence on locomotion elicited by contact with the walls of the experimental
      arena (thigmotaxis).

PMID- 9177137
TI  - Protein purification and nucleotide sequence of a lysozyme from the bacteria
      induced larvae of the fall webworm, Hyphantria cunea.
AB  - A protein with lytic activity against Micrococcus luteus was purified from the
      hemolymph of the fall webworm, Hyphantria cunea, larvae challenged with live E.
      coli. A bacteriolytic protein of about 14,000 daltons in mass was purified by
      cation exchange chromatography and reverse-phased HPLC. The optimum pH and
      optimum temperature range for activity were around pH 6.2 and 50 degrees C,
      respectively, in a 100 mM phosphate buffer. The amino-terminal amino acid
      sequence of this protein was determined and the corresponding cDNA was isolated
      and analyzed. The deduced protein of 142 amino acid residues was composed of a
      putative leader sequence of 20 residues and the mature enzyme of 122 residues.
      The cloned lysozyme gene was strongly induced in response to bacterial injection,
      implying that the enzyme is a part of the immune response of H. cunea. Comparison
      with other known lysozyme sequences shows that our lysozyme belongs to the
      chicken lysozyme.

PMID- 9177138
TI  - Role of the neuroendocrine complex in the control of adult diapause in the bean
      bug, Riptortus clavatus.
AB  - In the bean bug, Riptortus clavatus, allatectomy suppressed reproduction in
      adults reared under nondiapause-inducing long-day conditions, and transection of
      the nervi corporis allati induced reproduction in adults reared under diapause
      inducing short-day conditions. These effects of allatectomy and denervation were
      observed both in the morphology of reproductive organs and in the electrophoresis
      pattern of hemolymph proteins in both sexes. These results indicate that, in
      diapause adults, the brain suppresses the activity of the corpus allatum to
      secrete juvenile hormone through nervous pathways. The removal to the corpora
      cardiaca-carpus allatum complex in females not only inhibited ovarian
      development, as allatectomy did, but also prevented mature eggs in the oviduct
      from being laid. Therefore, it is assumed that the corpora cardiaca release an
      oviposition-stimulating substance.

PMID- 9177139
TI  - Growth rate of colon polyps and cancer.
AB  - Malignancy potential of colorectal polyps increases with size. The growth rate
      and destiny of each polyp is virtually unknown. It was recently shown that polyps
      smaller than 10 mm left in situ may partly regress or partly increase in size,
      whereas one quarter of polyps are unchanged after 3 years. Polyps smaller than 5
      mm show a mean increase in size, whereas polyps measuring 5 to 9 mm show a mean
      decrease in size. Methodologic problems with the measurement of polyps and cancer
      are discussed. More studies of polyp growth related to risk factors are
      warranted.

PMID- 9177140
TI  - Colon cancer screening. Sigmoidoscopy or colonoscopy.
AB  - Colorectal cancer is a common neoplasia with high morbidity and mortality. With
      endoscopy it is possible to identify its precursor lesion, the adenoma, and early
      localized cancer. Early detection and removal of adenomas can reduce the
      incidence and mortality of this disease. Studies using fecal occult blood testing
      (FOBT) and sigmoidoscopy for screening asymptomatic patients demonstrate a
      reduction in mortality from colorectal cancer. Colonoscopy, however, has the
      highest yield for detecting polyps. Most authorities and organizations now
      recommend screening the asymptomatic population over age 50 for colorectal
      neoplasia. The estimated cost of colon cancer screening is well within the
      benchmark figure of $40,000 per year of life saved, which is considered by the
      government to be cost effective. Controversies still exist regarding which colon
      cancer screening strategy is the most sensitive, specific, acceptable to the
      population, and cost effective. The American Cancer Society recommends a
      combination of FOBT and flexible sigmoidoscopy, but some experts believe that a
      one-time colonoscopy at age 60 may be a more cost-effective method. If the costs
      of colonoscopy are reduced, it is more cost effective than other techniques.
      Colonoscopy also may help to stratify at-risk patients, and those with negative
      initial colonoscopy may not need further screening. Advances in molecular biology
      may provide markers for screening or identifying people who are at high risk for
      colorectal neoplasia. This development may allow screening to be directed at high
      risk groups.

PMID- 9177141
TI  - Prevalence and incidence of colorectal adenomas and cancer in asymptomatic
      persons.
AB  - The prevalence of colorectal adenomatous polyps varies widely from country to
      country and is highly correlated with colorectal cancer incidence rates in each
      country. The prevalence of adenomas reported in older studies was based on
      autopsy findings and is higher than that in more recent studies based on
      endoscopy findings. Among asymptomatic, average-risk patients, adenoma prevalence
      averages approximately 10% in sigmoidoscopy studies and more than 25% in
      colonoscopy studies, whereas the prevalence of colorectal cancer among these
      patients is less than 1%. The cumulative incidence of new adenomas within 3 years
      after normal endoscopy averages about 7% by flexible sigmoidoscopy and 27% by
      colonoscopy.

PMID- 9177142
TI  - Marking and identifying colon lesions. Tattoos, clips, and radiology in imaging
      the colon.
AB  - Precise knowledge of a lesion's location in the colon is infrequently required.
      Occasionally, however, this information can be of critical clinical importance. A
      variety of endoscopic and radiologic techniques have been described to localize
      an area or site within the colon. Tissue staining or tattooing is the most
      reliable endoscopic method of colon lesion localization, and India ink provides a
      long-lasting and probably permanent tattoo of the site. Endoscopic clips are less
      reliable and remain cumbersome to use. Electronic imaging is an intriguing
      approach but remains experimental. Sites and lesions also can be identified by
      barium radiography or fluoroscopy, but these techniques involve added expenses
      and are not as reliable as tattooing with India ink.

PMID- 9177143
TI  - New methods of polypectomy.
AB  - The three most prominent advances in colonoscopic polypectomy are the submucosal
      injection of saline to ensure safety of polypectomy, the use of the small, or
      mini, snare for removal of most colon polyps, and the introduction of the argon
      plasma coagulator for the treatment of vascular abnormalities of the colon and
      the fulguration of residual adenoma at the base of sessile polyps with a
      noncontact technique. The role of Endoloop, endoscopic clips, and rubber band
      ligation for polypectomy is discussed.

PMID- 9177144
TI  - Colonic chromoscopy. A new perspective on polyps and flat adenomas.
AB  - A recent innovation in colonoscopy has been the use of chromoscopy. This
      technique allows better visualization of mucosal lesions by applying dyes to the
      mucosal surface. This article focuses on the principles and techniques of
      chromoscopy and magnification in the colon. The authors also describe the use of
      chromoscopy for differentiating polyps and detecting flat adenomas. The clinical
      significance of flat adenomas is reviewed.

PMID- 9177145
TI  - Computed tomographic colography and virtual colonoscopy.
AB  - CT colography (CTC) is a powerful new approach to imaging the colorectum and a
      promising screening tool for the detection of colorectal neoplasia. From data
      generated by a helical CT scan, CTC uses virtual reality technology to produce
      highly discriminant two- and three-dimensional images that permit a thorough and
      minimally invasive evaluation of the entire colorectum. A dynamic CTC display
      technique from the endoluminal perspective, called cf2virtual colonoscopy,cf1
      simulates colonoscopy by "flying" through the three-dimensional colon image. CTC
      offers potential advantages in diagnostic performance, safety, and patient
      acceptance over current screening approaches. Although early data suggest
      excellent colorectal polyp detection rates, this nascent technology will require
      rigorous clinical investigation and further refinements to assess adequately its
      place in the endoscopist's armamentarium.

PMID- 9177146
TI  - Cancer biology in ulcerative colitis and potential use in endoscopic
      surveillance.
AB  - Because patients with longstanding ulcerative colitis are at an increased risk
      for developing colorectal cancer, surveillance colonoscopy and colectomy for
      dysplasia or asymptomatic cancer is advised as a method of reducing cancer
      related mortality. Generally, the use of dysplasia as a criterion for a positive
      test in cancer surveillance has performed poorly. The emerging field of colon
      cancer genetics has identified several important tumor markers that have the
      potential to improve sensitivity for the detection of early neoplasia.
      Specifically, p53 tumor suppressor gene mutations, aneuploidy, and mucin
      associated sialosyl-Tn expression appear most promising for future use in
      surveillance programs.

PMID- 9177147
TI  - Real-time magnetic three-dimensional imaging of flexible endoscopy.
AB  - Because of the variability of the colonic anatomy from patient to patient,
      colonoscopy may be technically difficult to perform and teach, and lesions may be
      localized inaccurately by the endoscopist. Endoscopists understandably have
      abandoned fluoroscopy as an adjunct because of its expense, complexity, and
      potential hazard. The authors have developed a novel method of magnetic imaging
      that gives real-time views in simulated three dimensions of the endoscope
      configuration and the location of its tip in the abdomen. The system is
      inherently safe and easy to use, although it currently requires a catheter to be
      inserted into the instrumentation channel. Preliminary experience suggests that
      this approach will be a significant help to endoscopists performing colonoscopy,
      particularly to those who are currently learning or less experienced.

PMID- 9177148
TI  - Colonoscopy for diagnosis and treatment of severe lower gastrointestinal
      bleeding. Routine outcomes and cost analysis.
AB  - Approximately 10% to 15% of patients seen by gastroenterologists have severe,
      ongoing hematochezia, which most physicians assume is from a lower
      gastrointestinal (LGI) source. This article discusses current colonoscopic
      diagnosis and treatment of patients with severe LGI bleeding. The authors present
      their approach to the diagnosis and treatment of patients with severe
      hematochezia. They also discuss the specific lesions that cause this condition
      and the cost assessment of emergency colonoscopy compared to other approaches for
      diagnosis and treatment of severe hematochezia.

PMID- 9177149
TI  - Colonoscopy and acute colonic pseudo-obstruction.
AB  - There is no well-defined standard of care for the use of colonoscopy in the
      treatment of acute colonic pseudo-obstruction (ACPO). Colonoscopy can be helpful
      for ACPO, but it can be accompanied by complications, is not completely
      effective, and can be followed by recurrence. These possibilities must be weighed
      against the overall risk of spontaneous perforation, which is low but real. The
      use of colonoscopy therefore should be selective, and it should be performed by
      experts and accompanied generally by tube placement.

PMID- 9177150
TI  - Detection and treatment of angiodysplasia.
AB  - Angiodysplasias of the colon are difficult to detect but usually easy to treat.
      Colonoscopy is the most sensitive and specific method for detection, but
      angiography, endoscopic ultrasound, and nuclear medicine techniques are also
      useful. Emerging optical analysis techniques, such as remote endoscopic digital
      spectroscopy and enhancement with opioid antagonists, may improve detection
      rates. Treatment is performed conventionally with contact probes. Other methods
      of treatment include lasers, injection therapy, angiographic techniques, rubber
      band ligation, hormonal therapy, and surgical resection.

PMID- 9177151
TI  - Laparoscopic colectomy. Prospects and problems.
AB  - This article provides a fundamental review of laparoscopic colectomies. An
      overview of the physiology of laparascopic procedures is given as an introduction
      to the rationale of laparoscopic colectomies. A review of the current published
      literature including indications and an overview of laparoscopic bowel procedures
      for malignant diseases are presented.

PMID- 9177152
TI  - The PNAS way back then.

PMID- 9177153
TI  - Fas-ligand: privilege and peril.

PMID- 9177154
TI  - Rejection antigens in chemically induced tumors.

PMID- 9177155
TI  - Inhibitory receptors abound?

PMID- 9177156
TI  - What are the risks of low-level exposure to alpha radiation from radon?

PMID- 9177158
TI  - Cilia internal mechanism and metachronal coordination as the result of
      hydrodynamical coupling.
AB  - We present a simple but realistic model for the internal bend-generating
      mechanism of cilia, using parameters obtained from the analysis of data of the
      beat of a single cilium, and incorporate it into a recently developed dynamical
      model. Comparing the results to experimental data for two-dimensional beats, we
      demonstrate that the model captures the essential features of the motion,
      including many properties that are not built in explicitly. The beat pattern and
      frequency change in response to increased viscosity and the presence of
      neighboring cilia in a realistic fashion. Using the model, we are able to
      investigate multicilia configurations such as rows of cilia and two-dimensional
      arrays of cilia. When two adjacent model cilia start beating at different phase,
      they synchronize within two cycles, as observed in experiments in which two
      flagella beating out of phase are brought close together. Examination of various
      multicilia configurations shows that metachronal patterns (i. e., beats with a
      constant phase difference between neighboring cilia) evolve autonomously. This
      provides modeling evidence in support of the conjecture that metachronism may
      occur as a self-organized phenomenon due to hydrodynamical interactions between
      the cilia.

PMID- 9177157
TI  - The mother-child union: the case of missing-self and protection of the fetus.

PMID- 9177159
TI  - Disruption of lysosomal targeting is associated with insecticidal potency of
      juvenile hormone esterase.
AB  - Juvenile hormone esterase (JHE; EC 3.1.1.1), which is intrinsically involved in
      regulation of development of some insect larvae, is rapidly removed from the
      hemolymph by the pericardial cells. Lys-29 and Lys-524, which are implicated in
      the degradation of JHE, were mutated to Arg. Neither the half-life of the
      modified JHE in the hemolymph nor the catalytic parameters were changed
      significantly, but when combined, these mutations resulted in apparent failure of
      lysosomal targeting in the pericardial cell complex. A hypothesis for the
      mechanism of reduced efficiency of lysosomal targeting is presented. Infection of
      larvae with a recombinant baculovirus expressing the modified JHE resulted in a
      50% reduction in feeding damage compared with larvae infected with the wild-type
      virus, thus demonstrating improved properties as a biological insecticide. These
      data demonstrate that alteration of specific residues of JHE that disrupted
      lysosomal targeting, dramatically increased the insecticidal activity of this
      protein.

PMID- 9177161
TI  - Hydrogenase genes from Rhizobium leguminosarum bv. viciae are controlled by the
      nitrogen fixation regulatory protein nifA.
AB  - Rhizobium leguminosarum bv. viciae expresses an uptake hydrogenase in symbiosis
      with peas (Pisum sativum) but, unlike all other characterized hydrogen-oxidizing
      bacteria, cannot express it in free-living conditions. The hydrogenase-specific
      transcriptional activator gene hoxA described in other species was shown to have
      been inactivated in R. leguminosarum by accumulation of frameshift and deletion
      mutations. Symbiotic transcription of hydrogenase structural genes hupSL
      originates from a -24/-12 type promoter (hupSp). A regulatory region located in
      the -173 to -88 region was essential for promoter activity in R. leguminosarum.
      Activation of hupSp was observed in Klebsiella pneumoniae and Escherichia coli
      cells expressing the K. pneumoniae nitrogen fixation regulator NifA, and in E.
      coli cells expressing R. meliloti NifA. This activation required direct
      interaction of NifA with the essential -173 to -88 regulatory region. However, no
      sequences resembling known NifA-binding sites were found in or around this
      region. NifA-dependent activation was also observed in R. etli bean bacteroids.
      NifA-dependent hupSp activity in heterologous hosts was also absolutely dependent
      on the RpoN sigma-factor and on integration host factor. Proteins immunologically
      related to integration host factor were identified in R. leguminosarum. The data
      suggest that hupSp is structurally and functionally similar to nitrogen fixation
      promoters. The requirement to coordinate nitrogenase-dependent H2 production and
      H2 oxidation in nodules might be the reason for the loss of HoxA in R.
      leguminosarum and the concomitant NifA control of hup gene expression. This
      evolutionary acquired control would ensure regulated synthesis of uptake
      hydrogenase in the most common H2-rich environment for rhizobia, the legume
      nodule.

PMID- 9177162
TI  - The NG domain of the prokaryotic signal recognition particle receptor, FtsY, is
      fully functional when fused to an unrelated integral membrane polypeptide.
AB  - Recent studies have revealed that Escherichia coli possesses an essential
      targeting system for integral membrane proteins, similar to the mammalian signal
      recognition particle (SRP) machinery. One essential protein in this system is
      FtsY, a homologue of the alpha-subunit of the mammalian SRP-receptor (SR-alpha).
      However, E. coli does not possess a close homologue of the integral membrane
      protein SR-beta, which anchors SR-alpha to the membrane. Moreover, although FtsY
      can be found as a peripheral membrane protein, the majority is found soluble in
      the cytoplasm. In this study, we obtained genetic and biochemical evidence that
      FtsY must be targeted to the membrane for proper function. We demonstrate that
      the essential membrane targeting activity of FtsY is mediated by a 198-residue
      long acidic N-terminal domain. This domain can be functionally replaced by
      unrelated integral membrane polypeptides, thus avoiding the need for specific
      FtsY membrane targeting factors. Therefore, the N terminus of FtsY constitutes an
      independent domain, which is required only for the targeting of the C-terminal NG
      domain of FtsY to the membrane.

PMID- 9177163
TI  - Site-specific crosslinking of mammalian U11 and u6atac to the 5' splice site of
      an AT-AC intron.
AB  - A rare class of introns with AT-AC at their termini recently has been identified
      in metazoan genes. Splicing of these introns requires a different set of small
      nuclear ribonucleoprotein particles (snRNPs) (U11, U12, U5, and U4atac/U6atac)
      compared with the snRNPs (U1, U2, U5, and U4/U6) required for splicing the
      majority of pre-mRNA introns, but otherwise little is known regarding the
      excision of AT-AC introns. Here we use site-specific 4-thiouridine (4SU)
      crosslinking analysis to dissect the mechanism of 5' splice site recognition
      during in vitro splicing of the AT-AC intron from the P120 pre-mRNA. Upon
      irradiation with 365-nm UV light, three P120 substrates, each with a single 4SU
      substitution near the 5' splice site (at position +2, +4, or +7), produce two
      early ATP-independent crosslinks with similar kinetics. For one of the
      substrates, P120-4SU+2, a third ATP-requiring crosslink forms as the two early
      crosslinks diminish. RNase H digestion coupled with Northern blotting indicates
      that the two early crosslinks generated with P120-4SU+2 contain the U11 small
      nuclear RNA. Reverse transcription-PCR followed by cloning and sequencing
      demonstrates that the third crosslink involves U6atac. The dynamic appearance of
      the three crosslinks correlates with the kinetics of the splicing reaction and
      suggests that the 5' splice site is recognized first by U11 and then by U6atac.
      Our results argue that the splicing of AT-AC introns is mechanistically similar
      to the splicing of the major class of introns and that the U11 and U6atac snRNPs
      in the AT-AC spliceosome fulfill analogous roles to U1 and U6, respectively, in
      the major spliceosome.

PMID- 9177164
TI  - Detecting and characterizing N-acyl-homoserine lactone signal molecules by thin
      layer chromatography.
AB  - Many Gram-negative bacteria regulate gene expression in response to their
      population size by sensing the level of acyl-homoserine lactone signal molecules
      which they produce and liberate to the environment. We have developed an assay
      for these signals that couples separation by thin-layer chromatography with
      detection using Agrobacterium tumefaciens harboring lacZ fused to a gene that is
      regulated by autoinduction. With the exception of N-butanoyl-L-homoserine
      lactone, the reporter detected acyl-homoserine lactones with 3-oxo-, 3-hydroxy-,
      and 3-unsubstituted side chains of all lengths tested. The intensity of the
      response was proportional to the amount of the signal molecule chromatographed.
      Each of the 3-oxo- and the 3-unsubstituted derivatives migrated with a unique
      mobility. Using the assay, we showed that some bacteria produce as many as five
      detectable signal molecules. Structures could be assigned tentatively on the
      basis of mobility and spot shape. The dominant species produced by Pseudomonas
      syringae pv. tabaci chromatographed with the properties of N-(3-oxohexanoyl)-L
      homoserine lactone, a structure that was confirmed by mass spectrometry. An
      isolate of Pseudomonas fluorescens produced five detectable species, three of
      which had novel chromatographic properties. These were identified as the 3
      hydroxy- forms of N-hexanoyl-, N-octanoyl-, and N-decanoyl-L-homoserine lactone.
      The assay can be used to screen cultures of bacteria for acyl-homoserine
      lactones, for quantifying the amounts of these molecules produced, and as an
      analytical and preparative aid in determining the structures of these signal
      molecules.

PMID- 9177165
TI  - The 2.1-A crystal structure of an archaeal preinitiation complex: TATA-box
      binding protein/transcription factor (II)B core/TATA-box.
AB  - Archaea possess a basal transcriptional apparatus that resembles that of
      eukaryotes. Here we report the 2.1-A crystal structure of the archaeal
      transcription factor complex formed by the TATA-box-binding protein (TBP), the
      transcription factor IIB homolog, and a DNA target, all from the hyperthermophile
      Pyrococcus woesei. The overall fold of these two basal transcription factors is
      essentially the same as that of their eukaryotic counterparts. However, in
      comparison with the eukaryotic complexes, the archaeal TBP-DNA interface is more
      symmetrical, and in this structure the orientation of the preinitiation complex
      assembly on the promoter is inverted with respect to that seen in all crystal
      structures of comparable eukaryotic systems. This study of the structural details
      of an archaeal transcription factor complex presents the opportunity to examine
      the evolution of the basal eukaryotic transcriptional apparatus from a
      stereochemical viewpoint and to extend our understanding of the physical
      biochemistry of transcriptional initiation.

PMID- 9177166
TI  - Wip1, a novel human protein phosphatase that is induced in response to ionizing
      radiation in a p53-dependent manner.
AB  - Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of
      cellular responses including cell cycle arrest and/or apoptosis. IR-induced G1
      arrest has been shown to depend on the presence of the tumor suppressor p53,
      which acts as a transcriptional activator of several genes. p53 also plays a role
      in the induction of apoptosis in response to DNA damage, and this pathway can be
      activated by both transcription-dependent and -independent mechanisms. Here we
      report the identification of a novel transcript whose expression is induced in
      response to IR in a p53-dependent manner, and that shows homology to the type 2C
      protein phosphatases. We have named this novel gene, wip1. In vitro, recombinant
      Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+
      dependence and relative insensitivity to okadaic acid. Studies performed in
      several cell lines revealed that wip1 accumulation following IR correlates with
      the presence of wild-type p53. The accumulation of wip1 mRNA following IR was
      rapid and transient, and the protein was localized to the nucleus. Similar to
      waf1, ectopic expression of wip1 in human cells suppressed colony formation.
      These results suggest that Wip1 might contribute to growth inhibitory pathways
      activated in response to DNA damage in a p53-dependent manner.

PMID- 9177167
TI  - The alpha-bungarotoxin binding site on the nicotinic acetylcholine receptor:
      analysis using a phage-epitope library.
AB  - The nicotinic acetylcholine receptor (AcChoR) is a ligand-gated ion channel that
      is activated upon binding of acetylcholine. alpha-Neurotoxins, in particular
      alpha-bungarotoxin (alpha-BTX), bind specifically and with high affinity to the
      AcChoR and compete with binding of the natural ligand. We employed a 15-mer phage
      display peptide library to select epitopes reacting with alpha-BTX. Phages
      bearing the motif YYXSSL as a consensus sequence were found to bind with high
      affinity to alpha-BTX. The library-derived peptide (MRYYESSLKSYPD) bears amino
      acid sequence similarities to a region of the alpha-subunit of the Torpedo muscle
      AcChoR, as well as of other muscle and neuronal AcChoRs that bind alpha-BTX. The
      library-derived peptide and the corresponding peptides containing residues 187
      199 of the Torpedo AcChoR alpha-subunit (WVYYTCCPDTPYL), as well as peptides
      analogous to the above region in the neuronal AcChoR (e.g., human alpha7;
      ERFYECCKEPYPD) that binds alpha-BTX, inhibit the binding of alpha-BTX to the
      intact Torpedo AcChoR with IC50 values of 10(-6) M. A synthetic peptide from a
      neuronal AcChoR that does not bind alpha-BTX (e.g., human alpha2; ERKYECCKEPYPD)
      which differs by just one amino acid from the homologous peptide from the alpha
      BTX-binding protein (alpha7)-i.e., Lys in alpha2 and Tyr in alpha7-does not
      inhibit the binding of alpha-BTX to Torpedo AcChoR. These results indicate the
      requirement for two adjacent aromatic amino acid residues for binding to alpha
      BTX.

PMID- 9177168
TI  - Three-dimensional solution structure of the complex of alpha-bungarotoxin with a
      library-derived peptide.
AB  - The solution structure of the complex between alpha-bungarotoxin (alpha-BTX) and
      a 13-residue library-derived peptide (MRYYESSLKSYPD) has been solved using two
      dimensional proton-NMR spectroscopy. The bound peptide adopts an almost-globular
      conformation resulting from three turns that surround a hydrophobic core formed
      by Tyr-11 of the peptide. The peptide fills an alpha-BTX pocket made of residues
      located at fingers I and II, as well as at the C-terminal region. Of the peptide
      residues, the largest contact area is formed by Tyr-3 and Tyr-4. These findings
      are in accord with the previous data in which it had been shown that substitution
      of these aromatic residues by aliphatic amino acids leads to loss of binding of
      the modified peptide with alpha-BTX. Glu-5 and Leu-8, which also remarkably
      contribute to the contact area with the toxin, are present in all the library
      derived peptides that bind strongly to alpha-BTX. The structure of the complex
      may explain the fact that the library-derived peptide binds alpha-BTX with a 15
      fold higher affinity than that shown by the acetylcholine receptor peptide
      (alpha185-196). Although both peptides bind to similar sites on alpha-BTX, the
      latter adopts an extended conformation when bound to the toxin [Basus, V., Song,
      G. & Hawrot, E. (1993) Biochemistry 32, 12290-12298], whereas the library peptide
      is nearly globular and occupies a larger surface area of alpha-BTX binding site.

PMID- 9177169
TI  - Assembly of a rod-shaped chimera of a trimeric GCN4 zipper and the HIV-1 gp41
      ectodomain expressed in Escherichia coli.
AB  - The HIV-1 envelope subunit gp41 plays a role in viral entry by initiating fusion
      of the viral and cellular membranes. A chimeric molecule was constructed centered
      on the ectodomain of gp41 without the fusion peptide, with a trimeric isoleucine
      zipper derived from GCN4 (pIIGCN4) on the N terminus and part of the trimeric
      coiled coil of the influenza virus hemagglutinin (HA) HA2 on the C terminus. The
      chimera pII-41-HA was overexpressed as inclusion bodies in bacteria and refolded
      to soluble aggregates that became monodisperse after treatment with protease.
      Either trypsin or proteinase K, used previously to define a protease-resistant
      core of recombinant gp41 [Lu, M., Blacklow, S. C. & Kim, P. S. (1995) Nat.
      Struct. Biol. 2, 1075-1082], removed about 20-30 residues from the center of gp41
      and all or most of the HA2 segment. Evidence is presented that the resulting
      soluble chimera, retaining the pIIGCN4 coiled coil at the N terminus, is an
      oligomeric highly alpha-helical rod about 130 A long that crystallizes. The
      chimeric molecule is recognized by the Fab fragments of mAbs specific for folded
      gp41. A similar chimera was assembled from the two halves of the molecule
      expressed separately in different bacteria and refolded together. Crystals from
      the smallest chimera diffract x-rays to 2.6-A resolution.

PMID- 9177170
TI  - Crystal structure of heat shock locus V (HslV) from Escherichia coli.
AB  - Heat shock locus V (HslV; also called ClpQ) is the proteolytic core of the ATP
      dependent protease HslVU in Escherichia coli. It has sequence similarity with the
      beta-type subunits of the eukaryotic and archaebacterial proteasomes. Unlike
      these particles, which display 72-point symmetry, it is a dimer of hexamers with
      62-point symmetry. The crystal structure of HslV at 3.8-A resolution, determined
      by isomorphous replacement and symmetry averaging, shows that in spite of the
      different symmetry of the particle, the fold and the contacts between subunits
      are conserved. A tripeptide aldehyde inhibitor, acetyl-Leu-Leu-norleucinal, binds
      to the N-terminal threonine residue of HslV, probably as a hemiacetal, relating
      HslV also functionally to the proteasomes of archaea and eukaryotes.

PMID- 9177172
TI  - Resolution of an early RecA-recombination intermediate by a junction-specific
      endonuclease.
AB  - The nucleoprotein filament formed on a circular single strand by Escherichia coli
      RecA protein in vitro can pair with homologous duplex DNA even when the latter
      lacks a free homologous end, but subsequent progression of the reaction through
      strand exchange requires an end in at least one strand of the duplex DNA. We
      purified from E. coli an endonuclease activity that cleaves the outgoing strand
      of duplex DNA at the junction of homologous and heterologous sequences in three
      stranded RecA-recombination intermediates. This endonuclease activity also
      cleaves specifically at the junctions of duplex and single-stranded regions in
      synthetic double-stranded oligonucleotides whose central portion consists of
      unpaired heterologous sequences. These activities are consistent with a role in
      recombination and repair of DNA.

PMID- 9177171
TI  - Evidence for a mediator cycle at the initiation of transcription.
AB  - Free and elongating (DNA-bound) forms of RNA polymerase II were separated from
      yeast. Most cellular polymerase II was found in the elongating fraction, which
      contained all enzyme phosphorylated on the C-terminal domain and none of the 15
      subunit mediator of transcriptional regulation. These and other findings suggest
      that mediator enters and leaves initiation complexes during every round of
      transcription, in a process that may be coupled to C-terminal domain
      phosphorylation.

PMID- 9177173
TI  - Transient aggregates in protein folding are easily mistaken for folding
      intermediates.
AB  - It has been questioned recently whether populated intermediates are important for
      the protein folding process or are artefacts trapped in nonproductive pathways.
      We report here that the rapidly formed intermediate of the spliceosomal protein
      U1A is an off-pathway artefact caused by transient aggregation of denatured
      protein under native conditions. Transient aggregates are easily mistaken for
      structured monomers and could be a general problem in time-resolved folding
      studies.

PMID- 9177174
TI  - Iron-sulfur cluster disassembly in the FNR protein of Escherichia coli by O2:
      [4Fe-4S] to [2Fe-2S] conversion with loss of biological activity.
AB  - The transcription factor FNR (fumarate nitrate reduction) requires the presence
      of an iron-sulfur (Fe-S) cluster for its function as a global transcription
      regulator in Escherichia coli when oxygen becomes scarce. To define the oxidation
      state and type of Fe-S cluster present in the active form of FNR, we have studied
      anaerobically purified FNR with Mossbauer spectroscopy. Our data showed that this
      form of FNR contained a [4Fe-4S]2+ cluster (delta = 0.45 mm/s; DeltaEQ = 1.22
      mm/s) and that the [4Fe-4S]2+ cluster was rapidly destroyed on exposure of FNR to
      air. Under these conditions, the yellow-green active form of FNR turned deep red;
      analysis of sulfide indicated that 70% of the labile sulfide was still present,
      suggesting that the Fe-S cluster had been converted into a different form. Little
      [3Fe-4S] cluster was, however, detected by EPR. According to Mossbauer
      spectroscopy, the [4Fe-4S]2+ cluster was converted in about 60% yield to a [2Fe
      2S]2+ cluster (delta = 0.28 mm/s; DeltaEQ = 0.58 mm/s) following 17 min of
      exposure to air. The [2Fe-2S]2+ cluster form of FNR was much more stable to
      oxygen, but was unable to sustain biological activity (e.g., DNA binding).
      However, DNA binding and the absorption spectrum characteristic of the [4Fe-4S]2+
      cluster could be largely restored from the [2Fe-2S]2+ form when Cys, Fe, DTT, and
      the NifS protein were added. It has yet to be determined whether the form of FNR
      containing the [2Fe-2S]2+ cluster has any biological significance, e.g., as an in
      vivo intermediate that is more rapidly converted to the active form than the
      apoprotein.

PMID- 9177175
TI  - Cloning and functional expression of a novel glucuronyltransferase involved in
      the biosynthesis of the carbohydrate epitope HNK-1.
AB  - The HNK-1 carbohydrate epitope is characteristically expressed on a series of
      cell adhesion molecules and also on some glycolipids in the nervous system over a
      wide range of species from insect to mammal. The HNK-1 epitope is involved in
      cell-cell and/or cell-substrate interaction and recognition during the
      development of the nervous system. In this study, we isolated a novel
      glucuronyltransferase from rat brain, which is a key enzyme of the biosynthesis
      of the HNK-1 epitope on glycoproteins. Based on the partial amino acid sequences,
      we isolated cDNA encoding the glucuronyltransferase. The primary structure
      deduced from the cDNA sequence predicted a type II transmembrane protein with 347
      amino acids and had no detectable similarity with any other proteins of known
      functions, including glucuronyltransferases of the liver and olfactory
      epithelium. Expression of a soluble recombinant form of the enzyme in COS-1 cells
      produced an active glucuronyltransferase. The selective expression of the
      glucuronyltransferase gene in the nervous system was consistent with the almost
      exclusive localization of the HNK-1 epitope in the nervous system. Transfection
      of the glucuronyltransferase cDNA into COS-1 cells induced not only expression of
      the HNK-1 epitope on the cell surface but also marked morphological changes of
      the cells, suggesting that the HNK-1 epitope associates with the cell-substratum
      interaction.

PMID- 9177176
TI  - The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine
      aminopeptidase, MetAP-2.
AB  - The inhibition of new blood vessel formation (angiogenesis) is an effective means
      of limiting both the size and metastasis of solid tumors. The leading anti
      angiogenic compound, TNP-470, has proven to be effective in in vitro and in
      animal model studies, and is currently being tested in phase III antitumor
      clinical trials. Despite many detailed pharmacological studies, little is known
      of the molecular mode of action of TNP-470. Using a derivative of the TNP-470
      parent compound, the fungal metabolite, fumagillin, we have purified a mammalian
      protein that is selectively and covalently bound by this natural product. This
      fumagillin binding protein was found to be a metalloprotease, methionine
      aminopeptidase (MetAP-2), that is highly conserved between human and
      Saccharomyces cerevisiae. In the absence of MetAP-1, a distantly related
      methionine aminopeptidase, MetAP-2 function is essential for vegetative growth in
      yeast. We demonstrate that fumagillin selectively inhibits the S. cerevisiae
      MetAP-2 protein in vivo. The binding is highly specific as judged by the failure
      of fumagillin to inhibit MetAP-1 in vivo. Hence, these results identify MetAP-2
      as an important target of study in the analysis of the potent biological
      activities of fumagillin.

PMID- 9177177
TI  - The catalytic domain of lambda site-specific recombinase.
AB  - The Escherichia coli phage lambda integrase protein (Int) belongs to the large
      Int family of site-specific recombinases. It is a heterobivalent DNA binding
      protein that makes use of a high energy covalent phosphotyrosine intermediate to
      catalyze integrative and excisive recombination at specific chromosomal sites
      (att sites). A 293-amino acid carboxy-terminal fragment of Int (C65) has been
      cloned, characterized, and used to further dissect the protein. From this we have
      cloned and characterized a 188-amino acid, protease-resistant, carboxy-terminal
      fragment (C170) that we believe is the minimal catalytically competent domain of
      Int. C170 has topoisomerase activity and converts att suicide substrates to the
      covalent phosphotyrosine complexes characteristic of recombination intermediates.
      However, it does not show efficient binding to att site DNA in a native gel shift
      assay. We propose that lambda Int consists of three functional and structural
      domains: residues 1-64 specify recognition of "arm-type" DNA sequences distant
      from the region of strand exchange; residues 65-169 contribute to specific
      recognition of "core-type" sequences at the sites of strand exchange and possibly
      to protein-protein interactions; and residues 170-356 carry out the chemistry of
      DNA cleavage and ligation. The finding that the active site nucleophile Tyr-342
      is in a uniquely protease-sensitive region complements and reinforces the
      recently solved C170 crystal structure, which places Tyr-342 at the center of a
      17-amino acid flexible loop. It is proposed that C170 is likely to represent a
      generic Int family domain that thus affords a specific route to studying the
      chemistry of DNA cleavage and ligation in these recombinases.

PMID- 9177179
TI  - Gsalpha contains an unidentified covalent modification that increases its
      affinity for adenylyl cyclase.
AB  - Many G protein alpha subunits are dually acylated with myristate and palmitate or
      are palmitoylated on more than one cysteine residue near their N termini. The
      Galpha protein that activates adenylyl cyclase, alphas, is not myristoylated but
      can be reversibly palmitoylated. It appears that alphas contains another, as-yet
      unidentified covalent modification that decreases its apparent dissociation
      constant for adenylyl cyclase from 50 nM to <0. 5 nM. This modification is at or
      near the N terminus of the protein and is hydrophobic. Palmitoylation of native
      alphas does not account for its high affinity for adenylyl cyclase.

PMID- 9177178
TI  - Casein kinase II is a selective target of HIV-1 transcriptional inhibitors.
AB  - The identification of cellular factors that are required to complete various
      steps of the HIV-1 life cycle may lead to the development of new therapeutics.
      One key step, transcription from the integrated provirus, is inhibited by members
      of two distinct classes of compounds, the flavonoids and the benzothiophenes, via
      an unknown mechanism, possibly involving a cellular factor. A marked specificity
      toward inhibiting HIV-1 transcription is evidenced by the ability of drug-treated
      cells to retain their proliferative and differentiation capabilities. In
      addition, the compounds do not impede the activation and function of the
      transcriptional factor NF-kappaB. Here we report on the identification of several
      cellular proteins that mediate the HIV-1 transcriptional inhibitory property of
      the flavonoid chrysin. Chemical and immunologic analyses identified these
      cellular proteins as the individual subunits of casein kinase II (CKII). Though
      structurally unrelated to chrysin, an HIV-1 inhibitory benzothiophene also bound
      selectively to CKII. Both chrysin and the benzothiophenes inhibited human
      recombinant CKII enzymatic activity and showed competitive kinetics with respect
      to ATP, analogous to the classic CKII inhibitor 5, 6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB). Moreover, DRB potently inhibited HIV-1
      expression in chronically infected cells. CKII may regulate HIV-1 transcription
      by phosphorylating cellular proteins involved in HIV-1 transactivation that
      contain multiple CKII phosphorylation consensus sequences.

PMID- 9177180
TI  - Reaction of aflatoxin B1 exo-8,9-epoxide with DNA: kinetic analysis of covalent
      binding and DNA-induced hydrolysis.
AB  - The exo isomer of aflatoxin B1 (AFB1) 8,9-epoxide appears to be the only product
      of AFB1 involved in reaction with DNA and reacts with the N7 atom of guanine via
      an SN2 reaction from an intercalated state. Although the epoxide hydrolyzes
      rapidly in H2O (0.6 s-1 at 25 degrees C), very high yields of DNA adduct result.
      Experimental binding data were fit to a model in which the epoxide forms a
      reversible complex with calf thymus DNA (Kd = 0.43 mg ml-1, or 1.4 mM monomer
      equivalents) and reacts with guanine with a rate of 35 s-1. Stopped-flow kinetic
      analysis revealed attenuation of fluorescence in the presence of DNA that was
      dependent on DNA concentration. Kinetic spectral analysis revealed that this
      process represents conjugation of epoxide with DNA, with an extrapolated rate
      maximum of 42 s-1 and half-maximal velocity at a DNA concentration of 1.8 mg ml-1
      (5.8 mM monomer equivalents). The rate of hydrolysis of the epoxide was
      accelerated by calf thymus DNA in the range of pH 6-8, with a larger enhancement
      at the lower pH (increase of 0.23 s-1 at pH 6.2 with 0.17 mg DNA ml-1). The same
      rate enhancement effect was observed with poly[dA-dT].poly[dA-dT], in which the
      epoxide can intercalate but not form significant levels of N7 purine adducts, and
      with single-stranded DNA. The increased rate of hydrolysis by DNA resembles that
      reported earlier for epoxides of polycyclic hydrocarbons and is postulated to
      involve a previously suggested localized proton field on the periphery of DNA.
      The epoxide preferentially intercalates between base pairs, and the proton field
      is postulated to provide acid catalysis to the conjugation reaction.

PMID- 9177181
TI  - Proliferating cell nuclear antigen promotes DNA synthesis past template lesions
      by mammalian DNA polymerase delta.
AB  - Consistent with previous observations, proliferating cell nuclear antigen (PCNA)
      promotes DNA synthesis by calf thymus DNA polymerase delta (pol delta) past
      several chemically defined template lesions including model abasic sites, 8-oxo
      deoxyguanosine (dG) and aminofluorene-dG (but not acetylaminofluorene-dG). This
      synthesis is potentially mutagenic. The model abasic site was studied most
      extensively. When all deoxyribonucleoside triphosphates and a template bearing a
      model abasic site were present, DNA synthesis by pol delta beyond this site was
      stimulated 53-fold by addition of homologous PCNA. On an unmodified template
      (lacking any lesions), PCNA stimulated pol delta by 1.3-fold. Product analysis
      demonstrated that as expected from the "A-rule," fully and near-fully extended
      primers incorporated predominantly dAMP opposite the template lesion. Moreover,
      corollary primer extension studies demonstrated that in the presence (but not the
      absence) of PCNA, pol delta preferentially elongated primers containing dAMP
      opposite the model abasic template site. p21, a specific inhibitor of PCNA
      dependent DNA replication, inhibits PCNA-stimulated synthesis past model abasic
      template sites. We propose that DNA synthesis past template lesions by pol delta
      promoted by PCNA results from the fundamental mechanism by which PCNA stimulates
      pol delta, i.e., stabilization of the pol delta. template-primer complex.

PMID- 9177182
TI  - Deficiency of a protein-repair enzyme results in the accumulation of altered
      proteins, retardation of growth, and fatal seizures in mice.
AB  - L-Asparaginyl and L-aspartyl residues in proteins are subject to spontaneous
      degradation reactions that generate isomerized and racemized aspartyl
      derivatives. Proteins containing L-isoaspartyl and D-aspartyl residues can have
      altered structures and diminished biological activity. These residues are
      recognized by a highly conserved cytosolic enzyme, the protein L-isoaspartate(D
      aspartate) O-methyltransferase (EC 2.1.1.77). The enzymatic methyl esterification
      of these abnormal residues in vitro can lead to their conversion (i.e., repair)
      to normal L-aspartyl residues and should therefore prevent the accumulation of
      potentially dysfunctional proteins in vivo as cells and tissues age. Particularly
      high levels of the repair methyltransferase are present in the brain, although
      enyzme activity is present in all vertebrate tissues. To define the physiological
      relevance of this protein-repair pathway and to determine whether deficient
      protein repair would cause central nervous system dysfunction, we used gene
      targeting in mouse embryonic stem cells to generate protein L-isoaspartate(D
      aspartate) O-methyltransferase-deficient mice. Analyses of tissues from
      methyltransferase knockout mice revealed a striking accumulation of protein
      substrates for this enzyme in the cytosolic fraction of brain, heart, liver, and
      erythrocytes. The knockout mice showed significant growth retardation and
      succumbed to fatal seizures at an average of 42 days after birth. These results
      suggest that the ability of mice to repair L-isoaspartyl- and D-aspartyl
      containing proteins is essential for normal growth and for normal central nervous
      system function.

PMID- 9177183
TI  - Heparin-binding properties of selenium-containing thioredoxin reductase from HeLa
      cells and human lung adenocarcinoma cells.
AB  - Mammalian selenocysteine-containing thioredoxin reductase (TR) isolated from HeLa
      cells and from human lung adenocarcinoma cells was separated into two major
      enzyme species by heparin-agarose affinity chromatography. The low-affinity
      enzyme forms that were not retained on heparin agarose showed strong
      crossreactivity in immunoblot assays with anti-rat liver TR polyclonal
      antibodies, whereas the high-affinity enzyme forms that were retained by the
      heparin column were not detected. Both low and high heparin-affinity enzyme forms
      contained FAD, were indistinguishable on SDS/PAGE analysis, and exhibited similar
      catalytic activities in the NADPH-dependent DTNB [5,5'-dithiobis(2
      nitrobenzoate)] assay. The C-terminal amino acid sequences of 75Se-labeled
      tryptic peptides from lung adenocarcinoma low- and high heparin-affinity enzyme
      forms were identical to the predicted C-terminal sequence of human placental TR.
      These two determined peptide sequences were -Ser-Gly-Ala-Ser-Ile-Leu-Gln-Ala-Gly
      Cys-Secys-(Gly). Occurrence of the Se-carboxymethyl derivative of radioactive
      selenocysteine in the position corresponding to TGA in the gene confirmed that
      UGA is translated as selenocysteine. The presence of cysteine followed by a
      reactive selenocysteine residue in this C-terminal region of the protein may
      explain some of the unusual properties of the mammalian TRs.

PMID- 9177184
TI  - Interaction of the S phase regulator cdc18 with cyclin-dependent kinase in
      fission yeast.
AB  - The fission yeast gene cdc18(+) is required for entry into S phase and for
      coupling mitosis to the successful completion of S phase. Cdc18 is a highly
      unstable protein that is expressed only once per cell cycle at the G1/S boundary.
      Overexpression of Cdc18 causes a mitotic delay and reinitiation of DNA
      replication, suggesting that the inactivation of Cdc18 plays a role in preventing
      rereplication within a given cell cycle. In this paper, we present evidence that
      Cdc18 is associated with active cyclin-dependent kinase in vivo. We have
      expressed Cdc18 as a glutathione S-transferase fusion in fission yeast and
      demonstrated that the fusion protein is functional in vivo. We find that the
      Cdc18 fusion protein copurifies with a kinase activity capable of phosphorylating
      histone H1 and Cdc18. The activity was identified by a variety of methods as the
      cyclin-dependent kinase containing the product of the cdc2(+) gene. The amino
      terminus of Cdc18 is required for association with cyclin-dependent kinase, but
      the association does not require the consensus cyclin-dependent kinase
      phosphorylation sites in this region. Additionally, both G1/S and mitotic forms
      of cyclin-dependent kinase phosphorylate and interact with Cdc18. These
      interactions between Cdc18 and cyclin-dependent kinases suggest mechanisms by
      which cyclin-dependent kinases could activate the initiation of DNA replication
      and could prevent rereplication.

PMID- 9177185
TI  - Discovery of a second 15S-lipoxygenase in humans.
AB  - The lipoxygenase metabolism of arachidonic acid occurs in specific blood cell
      types and epithelial tissues and is activated in inflammation and tissue injury.
      In the course of studying lipoxygenase expression in human skin, we detected and
      characterized a previously unrecognized enzyme that at least partly accounts for
      the 15S-lipoxygenase metabolism of arachidonic acid in certain epithelial
      tissues. The cDNA was cloned from human hair roots, and expression of the mRNA
      was detected also in prostate, lung, and cornea; an additional 16 human tissues,
      including peripheral blood leukocytes, were negative for the mRNA. The cDNA
      encodes a protein of 676 amino acids with a calculated molecular mass of 76 kDa.
      The amino acid sequence has approximately 40% identity to the known human 5S-,
      12S-, and 15S-lipoxygenases. When expressed in HEK 293 cells, the newly
      discovered enzyme converts arachidonic acid exclusively to 15S
      hydroperoxyeicosatetraenoic acid, while linoleic acid is less well metabolized.
      These features contrast with the previously reported 15S-lipoxygenase, which
      oxygenates arachidonic acid mainly at C-15, but also partly at C-12, and for
      which linoleic acid is an excellent substrate. The different catalytic activities
      and tissue distribution suggest a distinct function for the new enzyme compared
      with the previously reported human 15S-lipoxygenase.

PMID- 9177186
TI  - Engineering subunit association of multisubunit proteins: a dimeric streptavidin.
AB  - A dimeric streptavidin has been designed by molecular modeling using effective
      binding free energy calculations that decompose the binding free energy into
      electrostatic, desolvation, and side chain entropy loss terms. A histidine-127 -
      > aspartic acid (H127D) mutation was sufficient to introduce electrostatic
      repulsion between subunits that prevents the formation of the natural tetramer.
      However, the high hydrophobicity of the dimer-dimer interface, which would be
      exposed to solvent in a dimeric streptavidin, suggests that the resulting
      molecule would have very low solubility in aqueous media. In agreement with the
      calculations, a streptavidin containing the H127D mutation formed insoluble
      aggregates. Thus, the major design goal was to reduce the hydrophobicity of the
      dimer-dimer interface while maintaining the fundamental structure. Free energy
      calculations suggested that the hydrophobicity of the dimer-dimer interface could
      be reduced significantly by deleting a loop from G113 through W120 that should
      have no apparent contact with biotin in a dimeric molecule. The resulting
      protein, containing both the H127D mutation and the loop deletion, formed a
      soluble dimeric streptavidin in the presence of biotin.

PMID- 9177187
TI  - Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in
      mammalian cells.
AB  - Protein regulators of G protein signaling (RGS proteins) were discovered as
      negative regulators of heterotrimeric G protein-mediated signal transduction in
      yeast and worms. Experiments with purified recombinant proteins in vitro have
      established that RGS proteins accelerate the GTPase activity of certain G protein
      alpha subunits (the reaction responsible for their deactivation); they can also
      act as effector antagonists. We demonstrate herein that either of two such RGS
      proteins, RGS4 or GAIP, attenuated signal transduction mediated by endogenous
      receptors, G proteins, and effectors when stably expressed as tagged proteins in
      transfected mammalian cells. The pattern of selectivity observed in vivo was
      similar to that seen in vitro. RGS4 and GAIP both attenuated Gi-mediated
      inhibition of cAMP synthesis. RGS4 was more effective than GAIP in blocking Gq
      mediated activation of phospholipase Cbeta.

PMID- 9177189
TI  - Folding funnels and energy landscapes of larger proteins within the capillarity
      approximation.
AB  - The characterization of protein-folding kinetics with increasing chain length
      under various thermodynamic conditions is addressed using the capillarity picture
      in which distinct spatial regions of the protein are imagined to be folded or
      trapped and separated by interfaces. The quantitative capillarity theory is based
      on the nucleation theory of first-order transitions and the droplet analysis of
      glasses and random magnets. The concepts of folding funnels and rugged energy
      landscapes are shown to be applicable in the large size limit just as for smaller
      proteins. An ideal asymptotic free-energy profile as a function of a reaction
      coordinate measuring progress down the funnel is shown to be quite broad. This
      renders traditional transition state theory generally inapplicable but allows a
      diffusive picture with a transition-state region to be used. The analysis unifies
      several scaling arguments proposed earlier. The importance of fluctuational fine
      structure both to the free-energy profile and to the glassy dynamics is
      highlighted. The fluctuation effects lead to a very broad trapping-time
      distribution. Considerations necessary for understanding the crossover between
      the mean field and capillarity pictures of the energy landscapes are discussed. A
      variety of mechanisms that may roughen the interfaces and may lead to a complex
      structure of the transition-state ensemble are proposed.

PMID- 9177188
TI  - Expression of a gene encoding a tRNA synthetase-like protein is enhanced in
      tumorigenic human myeloid leukemia cells and is cell cycle stage- and
      differentiation-dependent.
AB  - We cloned a tumorigenic phenotype-associated cDNA encoding a tRNA synthetase-like
      protein from an acute-phase human myeloid leukemia cell line. The cDNA was
      isolated by reiterative subtraction of cDNAs synthesized from tumor-generating
      parental leukemia cells versus those from a nontumorigenic variant of the same
      cells. The selected cDNA encodes a protein that is a close homolog of one subunit
      of prokaryote and yeast phenylalanyl-tRNA synthetase (PheRS). The expressed
      protein reacts specificially with polyclonal antibodies raised against mammalian
      phenylalanyl-tRNA synthetase. Expression of the gene (designated CML33) was
      directly confirmed by Northern blot hybridization to be substantially enhanced in
      the tumorigenic cells compared with the nontumorigenic variant. In addition,
      expression of CML33 in myeloid leukemia cells was sensitive to the stage of the
      cell cycle and to induction of differentiation. Although the relationship between
      these observations and the tumorigenic state of the human myeloid leukemia cell
      line used in these studies is unknown, to our knowledge, this is the first
      demonstration in mammalian cells of tumor-selective and cell cycle stage- and
      differentiation-dependent expression of a member of the tRNA synthetase gene
      family.

PMID- 9177190
TI  - Photochemical electron injection into redox-active proteins.
AB  - A new method is presented that makes it possible to inject electrons rapidly into
      redox-active proteins by means of a short light flash. Reduced carboxymethylated
      cytochrome c (CmCyt c) with carbon monoxide bound to the heme iron is mixed with
      the oxidized acceptor protein. Upon rapid photodissociation of CO the apparent
      redox potential of CmCyt c drops, resulting in electron transfer to the electron
      acceptor. In this study we have used mitochondrial cytochrome c oxidase as the
      acceptor protein, but the method also can be used to investigate electron
      transfer to other proteins that can interact with cytochrome c. In principle, it
      can be used with any redox protein into which a CO binding site at the heme iron
      can be engineered.

PMID- 9177191
TI  - Three-dimensional diffuse x-ray scattering from crystals of Staphylococcal
      nuclease.
AB  - We have developed methods for obtaining and characterizing three-dimensional maps
      of the reciprocal-space distribution of diffuse x-ray scattering from protein
      crystals, and have used the methods to study the nature of disorder in crystals
      of Staphylococcal nuclease. Experimentally obtained maps are 99.5% complete in
      the reciprocal-space resolution range of 10 A-2.5 A, show symmetry consistent
      with the P41 space group of the unit cell, and are highly reproducible.
      Quantitative comparisons of the data with three-dimensional simulations imply
      liquid-like motions of the protein [Caspar, D. L. D., Clarage, J., Salunke, D. M.
      & Clarage, M. (1988) Nature (London) 332, 659-662], with a correlation length of
      10 A and a root-mean-square displacement of 0.36 A.

PMID- 9177192
TI  - Ionic effects on the elasticity of single DNA molecules.
AB  - We used a force-measuring laser tweezers apparatus to determine the elastic
      properties of lambda-bacteriophage DNA as a function of ionic strength and in the
      presence of multivalent cations. The electrostatic contribution to the
      persistence length P varied as the inverse of the ionic strength in monovalent
      salt, as predicted by the standard worm-like polyelectrolyte model. However,
      ionic strength is not always the dominant variable in determining the elastic
      properties of DNA. Monovalent and multivalent ions have quite different effects
      even when present at the same ionic strength. Multivalent ions lead to P values
      as low as 250-300 A, well below the high-salt "fully neutralized" value of 450
      500 A characteristic of DNA in monovalent salt. The ions Mg2+ and Co(NH3)63+, in
      which the charge is centrally concentrated, yield lower P values than the
      polyamines putrescine2+ and spermidine3+, in which the charge is linearly
      distributed. The elastic stretch modulus, S, and P display opposite trends with
      ionic strength, in contradiction to predictions of macroscopic elasticity theory.
      DNA is well described as a worm-like chain at concentrations of trivalent cations
      capable of inducing condensation, if condensation is prevented by keeping the
      molecule stretched. A retractile force appears in the presence of multivalent
      cations at molecular extensions that allow intramolecular contacts, suggesting
      condensation in stretched DNA occurs by a "thermal ratchet" mechanism.

PMID- 9177193
TI  - Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding
      protein.
AB  - The atypical protein kinase C (PKC) member PKC-zeta has been implicated in
      several signal transduction pathways regulating differentiation, proliferation or
      apoptosis of mammalian cells. We report here the identification of a cytoplasmic
      and membrane-associated protein that we name zeta-interacting protein (ZIP) and
      that interacts with the regulatory domain of PKC-zeta but not classic PKCs. The
      structural motifs in ZIP include a recently defined ZZ zinc finger as a potential
      protein binding module, two PEST sequences and a novel putative protein binding
      motif with the consensus sequence YXDEDX5SDEE/D. ZIP binds to the pseudosubstrate
      region in the regulatory domain of PKC-zeta and is phosphorylated by PKC-zeta in
      vitro. ZIP dimerizes via the same region that promotes binding to PKC-zeta
      suggesting a competitive situation between ZIP:ZIP and ZIP:PKC-zeta complexes. In
      the absence of PKC-zeta proper subcellular localization of ZIP is impaired and we
      show that intracellular targeting of ZIP is dependent on a balanced interaction
      with PKC-zeta. Taking into account the recent isolation of ZIP by others in
      different contexts we propose that ZIP may function as a scaffold protein linking
      PKC-zeta to protein tyrosine kinases and cytokine receptors.

PMID- 9177194
TI  - Assembly and disassembly of a ternary complex of synaptobrevin, syntaxin, and
      SNAP-25 in the membrane of synaptic vesicles.
AB  - The synaptic membrane proteins synaptobrevin, syntaxin, and SNAP-25 form a
      ternary complex that can be disassembled by the ATPase N-ethylmaleimide-sensitive
      factor (NSF) in the presence of soluble cofactors (SNAP proteins). These steps
      are thought to represent molecular events involved in docking and subsequent
      exocytosis of synaptic vesicles. Using two independent and complementary
      approaches, we now report that such ternary complexes form in the membrane of
      highly purified and monodisperse synaptic vesicles in the absence of the plasma
      membrane. Furthermore, the complexes are reversibly dissociated by NSF and SNAP
      proteins. Thus, ternary complexes can be assembled and disassembled while all
      three proteins are anchored as neighbors in the same membrane, suggesting that
      NSF is involved in priming synaptic vesicles for exocytosis.

PMID- 9177195
TI  - Expression of an Arabidopsis plasma membrane aquaporin in Dictyostelium results
      in hypoosmotic sensitivity and developmental abnormalities.
AB  - The rd28 gene of Arabidopsis thaliana encodes a water channel protein, or
      aquaporin, of the plasma membrane. A construct in which transcription of the rd28
      cDNA is controlled by the Dictyostelium actin15 promoter was transformed into
      Dictyostelium discoideum cells. Transformants contained RD28 protein in their
      plasma membranes. When shifted to a low-osmotic-strength buffer, cells expressing
      rd28 swelled rapidly and burst, indicating that the plant aquaporin allowed rapid
      water entry in the amoebae. The rate of osmotic lysis was a function of the
      osmotic pressure of the buffer. We also selected transformants in which the
      expression of the rd28 cDNA is driven by the promoter of the prespore cotB gene.
      These transformants accumulated rd28 mRNA uniquely in prespore cells. In low
      osmotic-strength buffer, the cotB::rd28 cells aggregated and formed normally
      proportioned slugs but failed to form normal fruiting bodies. The number of
      spores was reduced 20-fold, and the stalks of the fruiting bodies were abnormally
      short. The consequences of expressing RD28 in prespore cells could be partially
      overcome by increasing the osmolarity of the medium. Under these conditions, the
      cotB::rd28 cells formed fruiting bodies of more normal appearance, and the number
      of viable spores increased slightly. Because prespore cells have to shrink and
      dehydrate to form spores, it was not unexpected that expression of an aquaporin
      would disrupt this process, but it was surprising to find that stalk
      differentiation was also affected by expression of rd28 in prespore cells. It
      appears that osmotic stress on prespore cells alters their ability to signal
      terminal differentiation in prestalk cells. The results provide independent
      confirmation that plant aquaporins can function in the cells of other organisms,
      and that D. discoideum can be used to study the properties of these water
      channels.

PMID- 9177197
TI  - A new member of the tumor necrosis factor/nerve growth factor receptor family
      inhibits T cell receptor-induced apoptosis.
AB  - By comparing untreated and dexamethasone-treated murine T cell hybridoma (3DO)
      cells by the differential display technique, we have cloned a new gene, GITR
      (glucocorticoid-induced tumor necrosis factor receptor family-related gene)
      encoding a new member of the tumor necrosis factor/nerve growth factor receptor
      family. GITR is a 228-amino acids type I transmembrane protein characterized by
      three cysteine pseudorepeats in the extracellular domain and similar to CD27 and
      4-1BB in the intracellular domain. GITR resulted to be expressed in normal T
      lymphocytes from thymus, spleen, and lymph nodes, although no expression was
      detected in other nonlymphoid tissues, including brain, kidney, and liver.
      Furthermore, GITR expression was induced in T lymphocytes upon activation by anti
      CD3 mAb, Con A, or phorbol 12-myristate 13-acetate plus Ca-ionophore treatment.
      The constitutive expression of a transfected GITR gene induced resistance to anti
      CD3 mAb-induced apoptosis, whereas antisense GITR mRNA expression lead to
      increased sensitivity. The protection toward T cell receptor-induced apoptosis
      was specific, because other apoptotic signals (Fas triggering, dexamethasone
      treatment, or UV irradiation) were not modulated by GITR transfection. Thus, GITR
      is a new member of tumor necrosis factor/nerve growth factor receptor family
      involved in the regulation of T cell receptor-mediated cell death.

PMID- 9177196
TI  - Aberrant retention of tyrosinase in the endoplasmic reticulum mediates
      accelerated degradation of the enzyme and contributes to the dedifferentiated
      phenotype of amelanotic melanoma cells.
AB  - The loss of tyrosinase, the key enzyme in melanin synthesis, has been implicated
      in the dedifferentiation of malignant melanocytes. The presence of tyrosinase
      transcripts and antigenic peptides in melanoma tumors prompted us to investigate
      whether the basis for the loss of the enzyme was proteolytic degradation. Toward
      this aim, we followed the kinetics of synthesis, degradation, processing,
      chaperone binding, inhibitor sensitivity, and subcellular localization of
      tyrosinase in normal and malignant melanocytes. We found that, in amelanotic
      melanoma cell lines, tyrosinase failed to reach the melanosome, the organelle for
      melanin synthesis, because it was retained in the endoplasmic reticulum (ER) and
      then degraded. Tyrosinase appeared mostly as a 70-kDa core-glycosylated,
      endoglycosidase H-sensitive, immature form bound to the ER chaperone calnexin and
      had a life-span of only 25% of normal. Maturation and transit from the ER to the
      Golgi compartment was facilitated by lowering the temperature of incubation to 31
      degrees C. Several proteasome inhibitors caused the accumulation of an
      approximately 60-kDa tyrosinase doublet that was more prominent in malignant than
      in normal melanocytes and promoted, to various degrees, the maturation of
      tyrosinase in melanoma cells and the translocation of the enzyme to melanosomes.
      The appearance of ubiquitinated tyrosinase after treatment of normal melanocytes
      with N-acetyl-L-leucinyl-L-leucinal-L-norleucinal reinforced our notion that some
      tyrosinase is normally degraded by proteasomes. Proteolysis of tyrosinase by
      proteasomes is consistent with the production of antigenic tyrosinase peptides
      that are presented to the immune system by major histocompatibility complex class
      I molecules.

PMID- 9177199
TI  - Assembly and positioning of microtubule asters in microfabricated chambers.
AB  - Intracellular organization depends on a variety of molecular assembly processes;
      while some of these have been studied in simplified cell-free systems, others
      depend on the confined geometry of cells and cannot be reconstructed using bulk
      techniques. To study the latter processes in vitro, we fabricated microscopic
      chambers that simulate the closed environment of cells. We used these chambers to
      study the positioning of microtubule asters. Microtubule assembly alone, without
      the action of molecular motors, is sufficient to position asters. Asters with
      short microtubules move toward the position expected from symmetry; however, once
      the microtubules become long enough to buckle, symmetry is broken. Calculations
      and experiments show that the bending-energy landscape has multiple minima.
      Microtubule dynamic instability modifies the landscape over time and allows
      asters to explore otherwise inaccessible configurations.

PMID- 9177198
TI  - Intracellular structures of normal and aberrant Plasmodium falciparum malaria
      parasites imaged by soft x-ray microscopy.
AB  - Soft x-ray microscopy is a novel approach for investigation of intracellular
      organisms and subcellular structures with high spatial resolution. We used x-ray
      microscopy to investigate structural development of Plasmodium falciparum malaria
      parasites in normal and genetically abnormal erythrocytes and in infected
      erythrocytes treated with cysteine protease inhibitors. Investigations in normal
      red blood cells enabled us to recognize anomalies in parasite structures
      resulting from growth under unfavorable conditions. X-ray microscopy facilitated
      detection of newly elaborated structures in the cytosol of fixed, unstained,
      intact erythrocytes, redistribution of mass (carbon) in infected erythrocytes,
      and aberrant parasite morphology. In cysteine protease inhibitor-treated,
      infected erythrocytes, high concentrations of material were detected in abnormal
      digestive vacuoles and aggregated at the parasite plasma membrane. We have
      demonstrated that an abnormal host erythrocyte skeleton affects structural
      development of parasites and that this aberrant development can be detected in
      the following generation when parasites from protein 4.1-deficient red blood
      cells infect normal erythrocytes. This work extends our current understanding of
      the relationship between the host erythrocyte membrane and the intraerythrocytic
      malaria parasite by demonstrating for the first time that constituents of the
      erythrocyte membrane play a role in normal parasite structural development.

PMID- 9177200
TI  - Insulin-like growth factor II signaling through the insulin-like growth factor
      II/mannose-6-phosphate receptor promotes exocytosis in insulin-secreting cells.
AB  - The insulin-like growth factor II (IGF-II)/mannose-6-phosphate (M-6-P) receptor
      is known to participate in endocytosis as well as sorting of lysosomal enzymes
      and is involved in membrane trafficking through rapid cycling between cytosolic
      membrane compartments and the plasma membrane. Here we demonstrate that IGF-II,
      acting through the IGF-II/M-6-P receptor, promotes exocytosis of insulin in the
      pancreatic beta cell. The effect of IGF-II was evoked at nonstimulatory
      concentrations of glucose, was mediated by a pertussis toxin sensitive GTP
      binding protein, was dependent on protein kinase C-induced phosphorylation, and
      was independent of changes in cytoplasmic free Ca2+ concentration. Since the
      applied concentration of IGF-II is within the range normally found free in
      circulation in humans, this novel signaling pathway for the IGF-II/M-6-P receptor
      is likely to be involved in modulation of insulin exocytosis under physiological
      conditions.

PMID- 9177201
TI  - Glial cell line-derived neurotrophic factor-dependent RET activation can be
      mediated by two different cell-surface accessory proteins.
AB  - Glial cell line-derived neurotrophic factor (GDNF)-dependent activation of the
      tyrosine kinase receptor RET is necessary for kidney and enteric neuron
      development, and mutations in RET are associated with human diseases. Activation
      of RET by GDNF has been shown to require an accessory component, GDNFR-alpha
      (RETL1). We report the isolation and characterization of rat and human cDNAs for
      a novel cell-surface associated accessory protein, RETL2, that shares 49%
      identity with RETL1. Both RETL1 and RETL2 can mediate GDNF dependent
      phosphorylation of RET, but they exhibit different patterns of expression in
      fetal and adult tissues. The most striking differences in expression observed
      were in the adult central and peripheral nervous systems. In addition, the
      mechanisms by which the two accessory proteins facilitate the activation of RET
      by GDNF are quite distinct. In vitro binding experiments with soluble forms of
      RET, RETL1 and RETL2 demonstrate that while RETL1 binds GDNF tightly to form a
      membrane-associated complex which can then interact with RET, RETL2 only forms a
      high affinity complex with GDNF in the presence of RET. This strong RET
      dependence of the binding of RETL2 to GDNF was confirmed by FACS analysis on
      RETL1 and RETL2 expressing cells. Together with the recent discovery of a GDNF
      related protein, neurturin, these data raise the possibility that RETL1 and RETL2
      have distinctive roles during development and in the nervous system of the adult.
      RETL1 and RETL2 represent new candidate susceptibility genes and/or modifier loci
      for RET-associated diseases.

PMID- 9177202
TI  - Site-specific de-N-glycosylation of diglycosylated ovalbumin in hen oviduct by
      endogenous peptide: N-glycanase as a quality control system for newly synthesized
      proteins.
AB  - Hen ovalbumin (OVA) is known to exist as a singly N-glycosylated form with a
      glycan chain on Asn-292 in egg white. Previous studies showed that di-N
      glycosylated form of OVA [Di-OVA; CHO-Asn-292/CHO-Asn-311 (CHO, N-glycan chain)],
      which has two N-glycan chains on Asn-292 and Asn-311, was expressed only
      transiently in hen oviduct. Di-OVA was not found in egg white, suggesting that
      this form cannot be secreted normally and may possibly be converted to mono-N
      glycosylated OVA (CHO-Asn-292/Asp-311) by the action of peptide:N-glycanase
      (PNGase) during synthesis and secretion. In this study, we have identified the
      putative PNGase activity in the homogenate of hen oviduct, purified 1,000-fold,
      and designated as PNGase HO. We examined the reactivity of Di-OVA to PNGase HO
      and found that this enzyme site-specifically cleaved off the glycan chain at Asn
      311 to convert Di-OVA into the mono-N-glycosylated form (CHO-Asn-292/Asp-311). In
      contrast, this enzyme was found not to act on the mono-N-glycosylated OVA (CHO
      Asn-292/Asn-311) found in egg white when it was tested as a substrate. The
      present findings support our view that de-N-glycosylation catalyzed by PNGase may
      be involved in quality control of newly synthesized proteins by converting its
      diglycosylated form into the mono-N-glycosylated form that can be secreted.
      However, the alternative possibility that de-N-glycosylation may trigger
      cytosolic degradation of the aberrantly glycosylated glycoprotein cannot be ruled
      out.

PMID- 9177203
TI  - Functional dissection of the Drosophila enhancer of split protein, a suppressor
      of neurogenesis.
AB  - The Enhancer of split [E(spl)] gene complex of Drosophila comprises seven related
      genes encoding a special type of basic helix-loop-helix proteins, the function of
      which is to suppress the neural developmental fate. One of these proteins is
      E(spl) itself. To gain insight into the structural requirements for E(spl)
      function, we have expressed a large number of deletion variants in transgenic
      flies. Three protein domains were identified as essential for suppression of
      bristle development: the carboxyl-terminal tetrapeptide WRPW, the region
      comprising the putative helix III and helix IV, and the region between helix IV
      and the WRPW motif. Lack of the basic helix-loop-helix domain, helix III or IV,
      only partially inhibits the suppressor activity of the protein. Truncated
      variants that lack all the regions carboxyl-terminal to helix IV elicit the
      development of additional neural progenitors, and thus act as dominant-negative
      variants. All these results suggest that E(spl) suppresses neural development by
      direct interaction with other proteins, such as groucho and the proneural
      proteins.

PMID- 9177204
TI  - Targeted gene expression without a tissue-specific promoter: creating mosaic
      embryos using laser-induced single-cell heat shock.
AB  - We have developed a method to target gene expression in the Drosophila embryo to
      a specific cell without having a promoter that directs expression in that
      particular cell. Using a digitally enhanced imaging system to identify single
      cells within the living embryo, we apply a heat shock to each cell individually
      by using a laser microbeam. A 1- to 2-min laser treatment is sufficient to induce
      a heat-shock response but is not lethal to the heat-shocked cells. Induction of
      heat shock was measured in a variety of cell types, including neurons and somatic
      muscles, by the expression of beta-galactosidase from an hsp26-lacZ reporter
      construct or by expression of a UAS target gene after induction of hsGAL4. We
      discuss the applicability of this technique to ectopic gene expression studies,
      lineage tracing, gene inactivation studies, and studies of cells in vitro. Laser
      heat shock is a versatile technique that can be adapted for use in a variety of
      research organisms and is useful for any studies in which it is desirable to
      express a given gene in only a distinct cell or clone of cells, either
      transiently or constitutively, at a time point of choice.

PMID- 9177205
TI  - Essential role of a kinesin-like protein in Arabidopsis trichome morphogenesis.
AB  - Little is known about how cell shape is controlled. We are using the
      morphogenesis of trichomes (plant hairs) on the plant Arabidopsis thaliana as a
      model to study how cell shape is controlled. Wild-type Arabidopsis trichomes are
      large, single epidermal cells with a stalk and three or four branches, whereas in
      zwichel (zwi) mutants the trichomes have a shortened stalk and only two branches.
      To further understand the role of the ZWI gene in trichome morphogenesis we have
      cloned the wild-type ZWICHEL (ZWI) gene by T-DNA tagging, and report here that it
      encodes a member of the kinesin superfamily of microtubule motor proteins.
      Kinesin proteins transport diverse cellular materials in a directional manner
      along microtubules. Kinesin-like proteins are characterized by a highly conserved
      "head" region that comprises the motor domain, and a nonconserved "tail" region
      that is thought to participate in recognition and binding of the appropriate
      cargo.

PMID- 9177206
TI  - Promoter analysis in living zebrafish embryos identifies a cis-acting motif
      required for neuronal expression of GATA-2.
AB  - We have used zebrafish embryos to dissect the promoter activity of a gene with a
      complex expression pattern during embryogenesis. GATA-2 is a transcription factor
      required for hematopoiesis and is dynamically expressed in hematopoietic tissues
      and in the central nervous system. Using constructs containing zebrafish GATA-2
      genomic flanking sequences and the green fluorescent protein (GFP) reporter gene,
      we demonstrate that distinct regulatory domains are required for hematopoietic,
      enveloping layer (EVL), and neuronal expression of GATA-2. During gastrulation,
      GFP expression is confined to the ventral ectoderm and lateral mesoderm and is
      lacking in the dorsal shield. Cells derived from the regions expressing GFP give
      rise to hematopoietic progenitors, EVL cells, and neurons. Deletion analysis of
      the 7.3-kb GATA-2 promoter region revealed that a 1.1-kb DNA sequence is critical
      for expression of GATA-2 in neurons. Fine mapping revealed that a 31-bp region is
      required for neuron enhancer activity, and mutagenesis showed that the DNA motif
      CCCTCCT is essential for GATA-2 promoter activity in the central nervous system
      of zebrafish. Our use of zebrafish embryos can be exploited as a whole animal
      system for the dissection of any developmentally regulated vertebrate promoter.

PMID- 9177207
TI  - Targeted null-mutation in the vascular endothelial-cadherin gene impairs the
      organization of vascular-like structures in embryoid bodies.
AB  - Vascular endothelial-cadherin (VE-cadherin) is exclusively expressed in
      endothelial cells and is strictly located at cell-to-cell junctions. As the other
      members of the cadherin family, VE-cadherin is able to mediate a homotypic type
      of cellular interaction in a Ca2+-dependent manner. In the mouse embryo, VE
      cadherin transcripts are detected at the earliest stages of vascular development.
      To ascertain if VE-cadherin expression is required for the assembly of
      endothelial cells into vascular structures, we generated VE-cadherin-negative
      mouse embryonic stem cells (VE-cadherin-/- ES cells) by gene targeting and
      examined the consequences on vascular development of ES-derived embryoid bodies
      (EBs). In contrast to wild-type EBs, we observed that endothelial cells remained
      dispersed and failed to organize a vessel-like pattern in VE-cadherin-/- ES
      derived EBs. However, dispersed VE-cadherin-/- ES-derived endothelial cells
      expressed a large range of other endothelial markers. Moreover, the targeted null
      mutation in the VE-cadherin locus did not interfere with the hematopoietic
      differentiation potential of ES cells. These in vitro experiments are consistent
      with a pivotal role of VE-cadherin in vascular structure assembly.

PMID- 9177208
TI  - An in vitro tubulogenesis system using cell lines derived from the embryonic
      kidney shows dependence on multiple soluble growth factors.
AB  - Interactions between the ureteric bud (UB) and metanephric mesenchyme are crucial
      for tubulogenesis during kidney development. Two immortalized cell lines derived
      from the day 11.5 embryonic kidney, UB cells, which appear to be epithelial
      (cytokeratin-positive, E-cadherin-positive, and ZO-1-positive by immunostaining)
      and BSN cells, which are largely mesenchymal (vimentin-positive, but negative for
      cytokeratin, cell surface E-cadherin, and cell surface ZO-1), were used to
      establish an in vitro tubulogenesis system. BSN cells expressed hepatocyte growth
      factor (HGF) and transforming growth factor-beta1 mRNAs, and its conditioned
      medium (BSN-CM) contained factors capable of activating the epidermal growth
      factor (EGF) receptor (EGFR). When UB cells were cultured in an extracellular
      matrix gel in the presence of the embryonic kidney or BSN-CM, the UB cells
      underwent morphogenetic changes characteristic of early in vitro branching
      tubulogenesis. These changes were largely inhibited by a combination of
      neutralizing anti-HGF antibodies and the EGFR inhibitor tyrphostin AG1478,
      suggesting that EGFR ligands, together with HGF, account for much of this early
      morphogenetic activity. Nevertheless, there was a significant fraction of
      tubulogenic activity that could not be inhibited, suggesting the existence of
      other soluble factors. Whereas HGF, EGF, transforming growth factor alpha, basic
      fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1), or a
      mixture of these growth factors, induced epithelial processes for up to 3 days,
      only IGF-1, possibly bFGF, and the mixture were able to sustain morphogenesis for
      longer periods, though not nearly to the same degree as BSN-CM. Moreover, only
      BSN-CM induced branching tubular structures with clear lumens, consistent with
      the existence of other soluble factors crucial for the formation and/or
      maintenance of branching tubular structures with lumens in vitro.

PMID- 9177209
TI  - Occurrence of plastid RNA editing in all major lineages of land plants.
AB  - RNA editing changes posttranscriptionally single nucleotides in chloroplast
      encoded transcripts. Although much work has been done on mechanistic and
      functional aspects of plastid editing, little is known about evolutionary aspects
      of this RNA processing step. To gain a better understanding of the evolution of
      RNA editing in plastids, we have investigated the editing patterns in ndhB and
      rbcL transcripts from various species comprising all major groups of land plants.
      Our results indicate that RNA editing occurs in plastids of bryophytes, fern
      allies, true ferns, gymnosperms, and angiosperms. Both editing frequencies and
      editing patterns show a remarkable degree of interspecies variation. Furthermore,
      we have found that neither plastid editing frequencies nor the editing pattern of
      a specific transcript correlate with the phylogenetic tree of the plant kingdom.
      The poor evolutionary conservation of editing sites among closely related species
      as well as the occurrence of single species-specific editing sites suggest that
      the differences in the editing patterns and editing frequencies are probably due
      both to independent loss and to gain of editing sites. In addition, our results
      indicate that RNA editing is a relatively ancient process that probably predates
      the evolution of land plants. This supposition is in good agreement with the
      phylogenetic data obtained for plant mitochondrial RNA editing, thus providing
      additional evidence for common evolutionary roots of the two plant organellar
      editing systems.

PMID- 9177210
TI  - Heme compounds in dinosaur trabecular bone.
AB  - Six independent lines of evidence point to the existence of heme-containing
      compounds and/or hemoglobin breakdown products in extracts of trabecular tissues
      of the large theropod dinosaur Tyrannosaurus rex. These include signatures from
      nuclear magnetic resonance and electron spin resonance that indicate the presence
      of a paramagnetic compound consistent with heme. In addition, UV/visible
      spectroscopy and high performance liquid chromatography data are consistent with
      the Soret absorbance characteristic of this molecule. Resonance Raman profiles
      are also consistent with a modified heme structure. Finally, when dinosaurian
      tissues were extracted for protein fragments and were used to immunize rats, the
      resulting antisera reacted positively with purified avian and mammalian
      hemoglobins. The most parsimonious explanation of this evidence is the presence
      of blood-derived hemoglobin compounds preserved in the dinosaurian tissues.

PMID- 9177211
TI  - Acquisition and amplification of a testis-expressed autosomal gene, SSL, by the
      Drosophila Y chromosome.
AB  - The acquisition of autosomal fertility genes has been proposed to be an important
      process in human Y chromosome evolution. For example, the Y-linked fertility
      factor DAZ (Deleted in Azoospermia) appears to have arisen after the
      transposition and tandem amplification of the autosomal DAZH gene. The Drosophila
      melanogaster Y chromosome contains tandemly repeated Su(Ste) units that are
      thought to affect male fertility as suppressors of the homologous X-linked
      Stellate repeats. Here we report the detection of a testis-expressed autosomal
      gene, SSL [Su(Ste)-like], that appears to be an ancestor of the Y-linked Su(Ste)
      units. SSL encodes a casein kinase 2 (CK2) beta-subunit-like protein. Its
      putative ORF shares extensive (45%) homology with the genuine beta-subunit of CK2
      and retains the conserved C-terminal and Glu/Asp-rich domains that are essential
      for CK2 holoenzyme regulation. SSL maps within region 60D1-2 of D. melanogaster
      and D. simulans polytene chromosomes. We present evidence that SSL was derived
      from the genuine betaCK2 gene by reverse transcription. This event resulted in
      the loss of the first three introns in the coding region of the SSL ancestor
      gene. Evolutionary analysis indicates that SSL has evolved under selective
      pressure at the translational level. Its sequence, especially in the 3' region,
      is much closer to the Y-linked Su(Ste) tandem repeats than to the betaCK2 gene.
      These results suggest that the acquisition of testis-specific autosomal genes may
      be important for the evolution of Drosophila as well as human Y chromosomes.

PMID- 9177212
TI  - Drosophila drop-dead mutations accelerate the time course of age-related markers.
AB  - Mutations of the drop-dead gene in Drosophila melanogaster lead to striking early
      death of the adult animal. At different times, after emergence from the pupa,
      individual flies begin to stagger and, shortly thereafter, die. Anatomical
      examination reveals gross neuropathological lesions in the brain. The life span
      of flies mutant for the drop-dead gene is four to five times shorter than for
      normal adults. That raises the question whether loss of the normal gene product
      might set into motion a series of events typical of the normal aging process. We
      used molecular markers, the expression patterns of which, in normal flies, change
      with age in a manner that correlates with life span. In the drop-dead mutant,
      there is an acceleration in the temporal pattern of expression of these age
      related markers.

PMID- 9177213
TI  - The peripheral blood fibrocyte is a potent antigen-presenting cell capable of
      priming naive T cells in situ.
AB  - Recent studies have identified a novel population of blood-borne cells, termed
      fibrocytes, that have a distinct cell surface phenotype
      (collagen+/CD13(+)/CD34(+)/CD45(+)), rapidly enter sites of tissue injury, and
      synthesize connective tissue matrix molecules. We found by flow cytometry that
      purified human fibrocytes express each of the known surface components that are
      required for antigen presentation, including class II major histocompatability
      complex molecules (HLA-DP, -DQ, and -DR), the costimulatory molecules CD80 and
      CD86, and the adhesion molecules CD11a, CD54, and CD58. Human fibrocytes induced
      antigen-presenting cell-dependent T cell proliferation when cultured with
      specific antigen and this proliferative activity was significantly higher than
      that induced by monocytes and nearly as high as that induced by purified
      dendritic cells. Mouse fibrocytes also were found to express the surface
      components required for antigen presentation and to function as potent APCs in
      vitro. Mouse fibrocytes pulsed in vitro with the HIV-proteins p24 or gp120 and
      delivered to a site of cutaneous injury were found to migrate to proximal lymph
      nodes and to specifically prime naive T cells. These data suggest that fibrocytes
      play an early and important role in the initiation of antigen-specific immunity.

PMID- 9177214
TI  - Peptides isolated from HLA-Cw*0304 confer different degrees of protection from
      natural killer cell-mediated lysis.
AB  - HLA class I molecules bind peptides derived from proteins degraded in the
      cytoplasm and display them for surveillance by the immune system. The recognition
      of HLA class I molecules by natural killer (NK) cells generally inhibits the
      lytic process. To investigate the role of peptides in the interaction between HLA
      class I molecules and NK receptors, we first had to identify representative
      endogenous peptides. Individual peptides bound to HLA-Cw*0304 were isolated and
      sequenced by tandem mass spectrometry. These peptides ranged in length from 8 to
      11 residues and shared an alanine at position 2 and a C-terminal leucine. The
      murine transporters associated with antigen processing (TAP)-deficient cell line
      RMA-S was transfected with HLA-Cw*0304 to test whether HLA molecules loaded with
      a single peptide could deliver the inhibitory signal to NK cells expressing
      p58.2, which is a killer cell inhibitory receptor known to interact with HLA
      molecules bearing the HLA-Cw3 public epitope. We found that, in the absence of
      exogenous peptides, the HLA-Cw*0304 transfectants were killed at levels
      comparable to untransfected RMA-S cells whereas protection from lysis required
      both HLA-Cw*0304 heavy chain expression and an exogenously added HLA-Cw*0304
      binding peptide. Importantly, not only were HLA-Cw*0304-binding peptides required
      for protection, but the ability of individual peptides to provide protection
      differed widely. These studies indicate that the ability to distinguish between
      subsets of peptides may be a general feature of HLA class I recognition by NK
      cells.

PMID- 9177215
TI  - Peyer's patch organogenesis is intact yet formation of B lymphocyte follicles is
      defective in peripheral lymphoid organs of mice deficient for tumor necrosis
      factor and its 55-kDa receptor.
AB  - Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin
      (LT) ligand and receptor system has recently revealed essential roles for these
      molecules in lymphoid tissue development and organization. Lymphotoxin-alphabeta
      (LTalphabeta)/lymphotoxin-beta receptor (LTbeta-R) signaling is critical for the
      organogenesis of lymph nodes and Peyer's patches and for the structural
      compartmentalization of the splenic white pulp into distinct B and T cell areas
      and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55
      tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B
      lymphocyte follicles, follicular dendritic cell networks, and germinal centers.
      In contrast to a previously described essential role for the p55TNF-R in Peyer's
      patch organogenesis, we show in this report that Peyer's patches are present in
      both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not
      essential for the organogenesis of this lymphoid organ. Furthermore, we show that
      in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T
      and B cell areas and a normal content and localization of dendritic cells is
      observed in both lymph nodes and Peyer's patches. However, although B cells are
      found to home normally within Peyer's patches and in the outer cortex area of
      lymph nodes, organized follicular structures and follicular dendritic cell
      networks fail to form. These results show that in contrast to LTalphabeta
      signaling, TNF signaling through the p55TNF-R is not essential for lymphoid
      organogenesis but rather for interactions that determine the cellular and
      structural organization of B cell follicles in all secondary lymphoid tissues.

PMID- 9177216
TI  - Transactivation by CIITA, the type II bare lymphocyte syndrome-associated factor,
      requires participation of multiple regions of the TATA box binding protein.
AB  - CIITA is a positive regulator of class II major histocompatibility complex gene
      transcription that has been found to be defective in one of the five
      complementation groups of class II major histocompatibility complex-negative cell
      lines. Its N-terminal region is capable of activating transcription from a
      reporter gene when fused to a DNA binding domain. We have investigated the
      mechanism of transactivation mediated by the CIITA activation domain by studying
      its role in the process of transcription initiation and elongation. Specifically
      the altered specificity TBP (TATA box binding protein) assay has been used to
      analyze the response of the CIITA activation domain to mutations in TBP known to
      disrupt its interaction with its associated general factors. Transactivation by
      CIITA was extremely sensitive to a mutation in TBP that in yeast is known to
      abolish VP16-mediated transcription but leaves basal transcription unaffected. A
      TBP mutant defective in interaction with TBP-associated factor TAFII250 also
      failed to mediate transactivation through the CIITA activation domain. Certain
      interactions between TBP and general factors that are specifically required for
      acidic activation domains were also required for CIITA-mediated transactivation
      to reach its full potential. Finally, like VP16, CIITA was able to stimulate
      elongation of transcription. Overall the mechanism of transactivation by the
      human B-cell-specific CIITA is very similar to that mediated by the herpes virus
      transactivator VP16 in the ways that have been tested.

PMID- 9177217
TI  - Specific complex formation between the type II bare lymphocyte syndrome
      associated transactivators CIITA and RFX5.
AB  - Two of the genes defective in the five complementation groups identified in the
      class II-negative bare lymphocyte syndrome or corresponding laboratory mutants
      have been cloned. One gene encodes a protein, RFX5, that is a member of the RFX
      family of DNA binding proteins. The other, CIITA, encodes a large protein with a
      defined acidic transcriptional activation domain; this protein does not interact
      with DNA. Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA
      binding domain activated transcription from a reporter construct containing GAL4
      sites in a cotransfection assay in the Raji human B cell line. However, these
      plasmids produced transcriptional activity in HeLa cells only in conjunction with
      interferon gamma stimulation, a condition in which expression of both CIITA and
      class II major histocompatibility complex surface proteins are induced.
      Furthermore, these plasmids were not active in RJ2.2.5, an in vitro mutagenized
      derivative of Raji in which both copies of CIITA are defective. Transcriptional
      activation by the RFX5 fusion protein could be restored in RJ2.2.5 by
      cotransfection with a CIITA expression plasmid. Finally, a direct interaction
      between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western
      blot assays. Thus, RFX5 can activate transcription only in cooperation with
      CIITA. RFX5 and CIITA associate to form a complex capable of activating
      transcription from class II major histocompatibility complex promoters. In this
      complex, promoter specificity is determined by the DNA binding domain of RFX5 and
      the general transcription apparatus is recruited by the acidic activation domain
      of CIITA.

PMID- 9177218
TI  - The epitopes for natural polyreactive antibodies are rich in proline.
AB  - "Natural" polyreactive antibodies, which bind in a nonspecific manner to a range
      of biological molecules both of self- and nonself- origin, are normal
      constituents of serum and are a significant part of the immune repertoire in many
      species, including humans. Autoantibodies to sTNF-R (the 55-kDa extracellular
      domain of the human receptor to tumor necrosis factor alpha) were affinity
      purified from normal human sera using immobilized sTNF-R. The isolated anti-sTNF
      R IgG bound both native and denatured forms of the receptor with low affinity.
      These antibodies also bound to different proteins and therefore are considered to
      be polyreactive. We used the anti-sTNF-R antibodies and purified polyreactive
      antibodies to mannose-specific lectin from garlic (Allium sativum) for screening
      a peptide library displayed on filamentous M13 phage. After the biopanning
      procedure, we failed to find epitopes with a consensus sequence; however, we
      found that proline is the most frequent amino acid in the selected phagotopes.
      Proline is commonly present at solvent-exposed sites in proteins, such as loops,
      turns, N-terminal first turn of helix, and random coils. Thus, structures
      containing proline can serve as conformation-dependent common "public" epitopes
      for polyreactive natural antibodies. Our findings may be important for
      understanding polyreactivity in general and for the significance of polyreactive
      natural antibodies in immunological homeostasis.

PMID- 9177219
TI  - Ancient origin of the complement lectin pathway revealed by molecular cloning of
      mannan binding protein-associated serine protease from a urochordate, the
      Japanese ascidian, Halocynthia roretzi.
AB  - Recent identification of a C3-like gene in sea urchins revealed the presence of a
      complement system in invertebrates. To elucidate further the components and
      function of the pre-vertebrate complement system, we attempted to isolate an
      ascidian (urochordata) C3 convertase. After identification of C3 cDNA from
      Halocynthia roretzi, a Japanese ascidian, reverse transcriptase-PCR amplification
      of hepatopancreas RNA was performed using primers encoding highly conserved amino
      acid sequences of the vertebrate Bf and C2 serine protease domain. Two candidate
      sequences were identified, and the corresponding cDNA clones were isolated from a
      hepatopancreas library. Surprisingly, neither clone is related to Bf/C2 but
      rather share the same domain structure of mammalian C1r/C1s/MASP (mannan binding
      protein-associated serine protease), and are more related evolutionarily to
      mammalian MASP than to mammalian C1r or C1s. The identification of the tunicate
      MASP clones, amplified with primers designed to amplify Bf or C2, suggests that
      the lectin pathway antedated the classical and alternative pathways of complement
      activation.

PMID- 9177220
TI  - CD27, a member of the tumor necrosis factor receptor family, induces apoptosis
      and binds to Siva, a proapoptotic protein.
AB  - Members of the tumor necrosis factor receptor (TNFR) superfamily are important
      for cell growth and survival. In addition to providing costimulatory signals for
      cell proliferation, ligation of both TNFR1 and Fas can result in programmed cell
      death or apoptosis. The underlying mechanism requires an intact 80-aa stretch
      present in the cytoplasmic tails of both TNFR1 and Fas, termed the death domain
      (DD). Here we show that CD27, a member of the TNFR family, expressed on discrete
      subpopulations of T and B cells and known to provide costimulatory signals for T
      and B cell proliferation and B cell Ig production, can also induce apoptosis. Co
      crosslinking of surface Ig receptors along with ligation of CD27 augments CD27
      mediated apoptosis. Unlike TNFR1 and Fas, the cytoplasmic tail of CD27 is
      relatively short and lacks the DD. Using the yeast two-hybrid system, we have
      cloned a novel protein (Siva) that binds to the CD27 cytoplasmic tail. It has a
      DD homology region, a box-B-like ring finger, and a zinc finger-like domain.
      Overexpression of Siva in various cell lines induces apoptosis, suggesting an
      important role for Siva in the CD27-transduced apoptotic pathway.

PMID- 9177221
TI  - In vivo role of B lymphocytes in somatic transgene immunization.
AB  - Immunity generated by in vivo inoculation of plasmid DNA is a straightforward and
      potentially valuable new approach to immunization. Little is known about the type
      of cells involved, the various immunological aspects, and the destiny of the
      transgene. In this report, we describe a system in which immunity is the result
      of in vivo targeting of B lymphocytes. This was accomplished using plasmid DNA
      encoding an immunoglobulin heavy-chain gene under the control of immunoglobulin
      promoter and enhancer elements. We show persistence of the transgene in splenic B
      lymphocytes for at least 3 months, i.e., the average life span of long-lived B
      lymphocytes in the mouse. The transgene could not be detected in any other
      lymphoid or nonlymphoid organs over a period of 6 months. We also established
      that the transgene is integrated in the host DNA. These studies bring new
      understanding to the events underlying the in vivo use of plasmid DNA. Moreover,
      the characteristics of this new approach make somatic transgene immunization a
      model system to study the immunogenicity of endogenous antigens in adult animals.

PMID- 9177222
TI  - Mast cell tumor necrosis factor alpha production is regulated by MEK kinases.
AB  - Mast cells synthesize and secrete specific cytokines and chemokines which play an
      important role in allergic inflammation. Aggregation of the high-affinity Fc
      receptor (FcepsilonRI) for immunoglobulin E (IgE) in MC/9 mouse mast cells
      stimulates the synthesis and secretion of tumor necrosis factor alpha (TNF
      alpha). FcepsilonRI aggregation activates several sequential protein kinase
      pathways, leading to increased activity of extracellular signal-regulated kinases
      (ERKs), c-Jun amino-terminal kinases (JNKs), and the p38 mitogen-activated
      protein (MAP) kinase. Inhibition of ERKs with the compound PD 098059 had little
      effect on FcepsilonRI-stimulated TNF-alpha production. Aggregation of FcepsilonRI
      stimulated MEK kinase 1 (MEKK1) activity, which activates JNK kinase (JNKK), the
      kinase that phosphorylates and activates JNKs. Expression of activated MEKK1
      (DeltaMEKK1) in MC/9 cells strongly stimulated JNK activity but only weakly
      stimulated p38 activity, and it induced a large activation of TNF-alpha promoter
      regulated luciferase gene expression. Inhibitory mutant JNK2 expressed in MC/9
      cells significantly blunted FcepsilonRI stimulation of TNF-alpha promoter-driven
      luciferase expression. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase,
      diminished FcepsilonRI-mediated TNF-alpha synthesis, significantly blunted JNK
      activation and TNF-alpha promoter-driven luciferase expression, and only weakly
      inhibited p38 kinase activation. Inhibition of NFkappaB activation resulting from
      DeltaMEKK1 expression or FcepsilonRI stimulation did not affect TNF-alpha
      promoter-driven luciferase expression. Our findings define a MEKK-regulated JNK
      pathway activated by FcepsilonRI that regulates TNF-alpha production in mast
      cells.

PMID- 9177223
TI  - Production of secretory immunoglobulin A by a single mammalian cell.
AB  - Secretory IgA (sIgA) plays a critical role in providing protection against
      infection at the mucosal surfaces. Normally, sIgA is the product of two different
      cell types with heavy, light, and J chains produced by the plasma cells, whereas
      secretory component (SC), a cleavage product of the polymeric immunoglobulin
      receptor (pIgR), is added during the transit of dimeric IgA through the
      epithelial cell layer. In the current study, by introducing a gene for the
      processed form of SC into a cell line that produces dimeric IgA, we have
      succeeded in creating a single cell that is able to produce and secrete
      covalently joined sIgA. To our knowledge, this is the first time it has been
      possible to efficiently produce large quantities of sIgA of defined specificity
      in mammalian cells. The sIgA made using this approach has great potential as an
      immunotherapeutic.

PMID- 9177224
TI  - Tissue-specific expression of the human prostate-specific antigen gene in
      transgenic mice: implications for tolerance and immunotherapy.
AB  - Human prostate-specific antigen (PSA) has been widely used as a serum marker for
      cancer of the prostate. The cell type-specific expression of PSA also makes it a
      potential tumor antigen for prostate cancer immunotherapy. Study of the
      immunological aspects of PSA within either normal or malignant prostate tissue
      has been hampered by the lack of a mouse model, because no PSA counterpart has
      been identified in mice. Using a 14-kb genomic DNA region that encompasses the
      entire human PSA gene and adjacent flanking sequences, we generated a series of
      human PSA transgenic mice. In the six independent lines of transgenic mice
      generated, the expression of the human PSA transgene, driven by its own cis
      acting regulatory elements, is specifically targeted to the prostate. Tissue
      distribution analysis demonstrated that PSA transgene expression closely follows
      the human expression pattern. Immunohistochemical analysis of the prostate tissue
      also showed that the expression of the PSA transgene is confined to the ductal
      epithelial cells. Despite expressing PSA as a self-antigen in the prostate, these
      transgenic mice were able to mount a cytotoxic immune response against PSA
      expressed by tumor cells, indicating that expression of the transgene has not
      resulted in complete nonresponsiveness. This transgenic mouse model will provide
      a well defined system to gain an insight into the mechanisms of nonresponsiveness
      to PSA, ultimately leading to strategies for immunotherapy of human prostate
      cancer using PSA as the target antigen.

PMID- 9177225
TI  - Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse
      sarcoma.
AB  - The molecular basis of the polymorphic tumor rejection antigens of chemically
      induced sarcomas of inbred mice remains a mystery, despite the discovery of these
      antigens over 40 years ago and their critical importance to the foundation of
      tumor immunology. In an analysis of a panel of BALB/c 3-methylcholanthrene
      induced tumors, we identified one tumor, CMS5, that elicited a strong cytotoxic T
      cell response with exquisite specificity for CMS5. A stable cloned line of T
      cells with this specificity (C18) was used to screen a CMS5 cDNA expression
      library. The gene encoding the C18-defined antigen was identified as a mutated
      form of a mouse mitogen-activated protein kinase, ERK2, and a peptide
      incorporating the resulting amino acid substitution (lysine to glutamine) was
      efficiently recognized by C18. Vaccination with this peptide elicited specific
      resistance to CMS5 challenge. Extensive efforts to isolate antigen-loss variants
      of CMS5 were unsuccessful, suggesting that the mutated mitogen-activated protein
      kinase is essential for maintenance of the malignant phenotype.

PMID- 9177226
TI  - High level expression of p27(kip1) and cyclin D1 in some human breast cancer
      cells: inverse correlation between the expression of p27(kip1) and degree of
      malignancy in human breast and colorectal cancers.
AB  - The expression of cyclin-dependent kinase inhibitor p27(kip1) in human tumors and
      normal tissues was investigated using a panel of novel anti-p27(kip1) mAbs. An
      inverse correlation between expression of p27(kip1) and cell proliferation was
      generally observed after analyzing its expression in 25 different normal human
      tissues. In some highly proliferative human breast cancer cells, however, high
      level p27(kip1) expression was seen, indicating the existence of a mechanism by
      which some growing tumor cells may tolerate this inhibitor of cell cycle
      progression. Detailed studies demonstrated a correlation between the high level
      expression of p27(kip1) and cyclin D1 in human breast cancer cells. There was
      also an inverse correlation between the expression of p27(kip1) and the degree of
      tumor malignancy in human breast and colorectal cancers, indicating that
      p27(kip1) may be a useful prognostic marker in these cancers.

PMID- 9177227
TI  - Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation.
AB  - We have studied mechanisms by which leptin overexpression, which reduces body
      weight via anorexic and thermogenic actions, induces triglyceride depletion in
      adipocytes and nonadipocytes. Here we show that leptin alters in pancreatic
      islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and
      uncoupling protein-2 (UCP-2). In animals infused with a recombinant adenovirus
      containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial
      and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of
      esterification declined in islets from hyperleptinemic rats. Islet UCP-2 mRNA
      rose 6-fold. All in vivo changes occurred in vitro in normal islets cultured with
      recombinant leptin, indicating direct extraneural effects. Leptin overexpression
      increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and
      subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese
      rats. By directly regulating the expression of enzymes of free fatty acid
      metabolism and of UCP-2, leptin controls intracellular triglyceride content of
      certain nonadipocytes, as well as adipocytes.

PMID- 9177228
TI  - Overexpression of angiotensin AT1 receptor transgene in the mouse myocardium
      produces a lethal phenotype associated with myocyte hyperplasia and heart block.
AB  - Previous studies have suggested that angiotensin II (Ang II) modulates cardiac
      contractility, rhythm, metabolism, and structure. However, it is unclear whether
      the cardiac effects are due to direct actions of Ang II on the myocardium or if
      they are due to secondary effects mediated through the hemodynamic actions of Ang
      II. In this study, we used the alpha-myosin heavy chain (alphaMHC) promoter to
      generate transgenic mice overexpressing angiotensin II type 1 (AT1a) receptor
      selectively in cardiac myocytes. The specificity of transgene expression in the
      transgenic offspring was confirmed by radioligand binding studies and reverse
      transcription-PCR. The offspring displayed massive atrial enlargement with
      myocyte hyperplasia at birth, developed significant bradycardia with heart block,
      and died within the first weeks after birth. Thus, direct activation of AT1
      receptor signaling in cardiac myocytes in vivo is sufficient to induce cardiac
      myocyte growth and alter electrical conduction.

PMID- 9177229
TI  - Polycystin: in vitro synthesis, in vivo tissue expression, and subcellular
      localization identifies a large membrane-associated protein.
AB  - The primary structure of polycystin predicts a large integral membrane protein
      with multiple cell recognition motifs, but its function remains unknown. Insight
      into polycystin's normal function and its role in the development of autosomal
      dominant polycystic kidney disease (PKD1) requires the assembly of an extensive
      collection of molecular reagents to examine its expression and create model
      systems for functional studies. Development of these crucial reagents has been
      complicated due to the presence of transcriptionally active homologous loci. We
      have assembled the authentic full-length PKD1 cDNA and demonstrated expression of
      polycystin in vitro. Polyclonal antibodies directed against distinct extra- and
      intracellular domains specifically immunoprecipitated in vitro translated
      polycystin. The panel of antibodies was used to determine localization of
      polycystin in renal epithelial and endothelial cell lines and tissues of fetal,
      adult, and cystic origins. In normal adult kidney and maturing fetal nephrons,
      polycystin expression was confined to epithelial cells of the distal nephron and
      vascular endothelial cells. Expression in the proximal nephron was only observed
      after injury-induced cell proliferation. Polycystin expression was confined to
      ductal epithelium in liver, pancreas, and breast, and restricted to astrocytes in
      normal brain. We report clear evidence for the membrane localization of
      polycystin by both tissue sections and by confocal microscopy in cultured renal
      and endothelial cells. Interestingly, when cultured cells made cell-cell contact,
      polycystin was localized to the lateral membranes of cells in contact. These data
      suggest that polycystin is likely to have a widespread role in epithelial cell
      differentiation and maturation and in cell-cell interactions.

PMID- 9177230
TI  - Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.
AB  - In the United States, blood donors are being screened for infection with human T
      cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect
      antibodies to the structural proteins of these viruses. Because patients with
      mycosis fungoides (MF) usually do not have such antibodies even though their
      cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether
      the prevalence of HTLV infection among healthy blood donors may also be
      underestimated by current means of testing. To examine this possibility, a study
      on specimens of relatives of mycosis fungoides patients (MFR) was begun. In
      addition, to collect data more expeditiously, a cohort of former injection drug
      users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern
      blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis
      for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of
      HIV-negative IDUs proved to be positive for HTLV, whereas routine serology
      identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter
      test subjects, the incidence of HTLV-I also proved to be 10 times higher than
      expected. Therefore, it is likely that among healthy blood donors infection with
      HTLV-I/II is more prevalent than is currently assumed. Since Tax is the
      transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to
      its gene product may be desirable in blood transfusion and tissue donor
      facilities.

PMID- 9177231
TI  - Quantitative neuropathology by high resolution magic angle spinning proton
      magnetic resonance spectroscopy.
AB  - We describe a method that directly relates tissue neuropathological analysis to
      medical imaging. Presently, only indirect and often tenuous relationships are
      made between imaging (such as MRI or x-ray computed tomography) and
      neuropathology. We present a biochemistry-based, quantitative neuropathological
      method that can help to precisely quantify information provided by in vivo proton
      magnetic resonance spectroscopy (1HMRS), an emerging medical imaging technique.
      This method, high resolution magic angle spinning (HRMAS) 1HMRS, is rapid and
      requires only small amounts of unprocessed samples. Unlike chemical extraction or
      other forms of tissue processing, this method analyzes tissue directly, thus
      minimizing artifacts. We demonstrate the utility of this method by assessing
      neuronal damage using multiple tissue samples from differently affected brain
      regions in a case of Pick disease, a human neurodegenerative disorder. Among
      different regions, we found an excellent correlation between neuronal loss shown
      by traditional neurohistopathology and decrease of the neuronal marker N
      acetylaspartate measured by HRMAS 1HMRS. This result demonstrates for the first
      time, to our knowledge, a direct, quantitative link between a decrease in N
      acetylaspartate and neuronal loss in a human neurodegenerative disease. As a
      quantitative method, HRMAS 1HMRS has potential applications in experimental and
      clinical neuropathologic investigations. It should also provide a rational basis
      for the interpretation of in vivo 1HMRS studies of human neurological disorders.

PMID- 9177232
TI  - A chemoattractant cytokine associated with granulomas in tuberculosis and
      silicosis.
AB  - Chronic inflammation and granuloma formation are associated with mononuclear cell
      infiltrates and are characteristic pathologic responses in tuberculosis. To
      identify host cell genes involved in tuberculous pathology, we screened
      macrophage cDNA libraries for genes induced by mycobacterial infection. One gene
      isolated in this screen, osteopontin (also known as early T lymphocyte activation
      protein 1 or Eta-1), was of particular interest because it is a cytokine and
      macrophage chemoattractant. Further study revealed that Mycobacterium
      tuberculosis infection of primary human alveolar macrophages causes a substantial
      increase in osteopontin gene expression. Osteopontin protein was identified by
      immunohistochemistry in macrophages, lymphocytes, and the extracellular matrix of
      pathologic tissue sections of patients with tuberculosis. Increased osteopontin
      expression also was found to be associated with silicosis, another granulomatous
      disease. The association of osteopontin with granulomatous pathology, together
      with the known properties of the protein, suggest that osteopontin may
      participate in granuloma formation. The strategy of identifying host genes whose
      expression is altered by infection thus can provide valuable clues to disease
      mechanisms and will be increasingly valuable as additional human genome sequences
      become available.

PMID- 9177233
TI  - Expression of Fas ligand in liver metastases of human colonic adenocarcinomas.
AB  - Fas ligand (FasL) plays a pivotal role in lymphocyte cytotoxicity and the
      maintenance of immunological homeostasis. Since FasL has been implicated in the
      existence of immunologically privileged body sites by inducing apoptosis of
      activated T lymphocytes, we investigated the expression of FasL in human colon
      cancers. We found that two out of seven primary tumors and all four hepatic
      metastatic tumors of surgically obtained colonic adenocarcinoma expressed FasL
      mRNA and protein, detected by reverse transcription-coupled PCR and by
      immunohistochemical staining, respectively. Expression of FasL was not detected
      in normal colonic epithelial cells. FasL mRNA was also expressed in some human
      colonic adenocarcinoma cell lines including SW480, SW1116, and LS180 cells. Cell
      surface-associated FasL was detected in these human colon cancer cells by
      fluorescence immunocytochemical staining. In addition, the expressed FasL was
      demonstrated to be functional, since coculture experiments using FasL-expressing
      SW480 cells resulted in apoptosis of Jurkat T leukemia cells that are sensitive
      to Fas-mediated apoptosis, and this process was specifically inhibited by the
      neutralizing anti-human FasL antibody. Thus, our findings and other data suggest
      an alternative mechanism that enables tumors to evade immune destruction by
      inducing apoptosis in activated T lymphocytes. Furthermore, constitutive
      expression of FasL in hepatic metastatic tumors suggests that FasL may also be
      important in their colonization in the liver through induction of apoptosis in
      the surrounding Fas-expressing hepatocytes.

PMID- 9177234
TI  - Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and
      CXCR4 domains.
AB  - The chemokine receptor CXCR4 functions as a fusion coreceptor for T cell tropic
      and dual-tropic HIV-1 strains. To identify regions of CXCR4 that are important
      for coreceptor function, CXCR4-CXCR2 receptor chimeras were tested for the
      ability to support HIV-1 envelope (env) protein-mediated membrane fusion.
      Receptor chimeras containing the first and second extracellular loops of CXCR4
      supported fusion by T tropic and dual-tropic HIV-1 and HIV-2 strains and binding
      of a monoclonal antibody to CXCR4, 12G5, that blocks CXCR4-dependent infection by
      some virus strains. The second extracellular loop of CXCR4 was sufficient to
      confer coreceptor function to CXCR2 for most virus strains tested but did not
      support binding of 12G5. Truncation of the CXCR4 cytoplasmic tail or mutation of
      a conserved DRY motif in the second intracellular loop did not affect coreceptor
      function, indicating that phosphorylation of the cytoplasmic tail and the DRY
      motif are not required for coreceptor function. The results implicate the
      involvement of multiple CXCR4 domains in HIV-1 coreceptor function, especially
      the second extracellular loop, though the structural requirements for coreceptor
      function were somewhat variable for different env proteins. Finally, a hybrid
      receptor in which the amino terminus of CXCR4 was replaced by that of CCR5 was
      active as a coreceptor for M tropic, T tropic, and dual-tropic env proteins. We
      propose that dual tropism may evolve in CCR5-restricted HIV-1 strains through
      acquisition of the ability to utilize the first and second extracellular loops of
      CXCR4 while retaining the ability to interact with the CCR5 amino-terminal
      domain.

PMID- 9177235
TI  - Intercellular adhesion molecule 1 knockout abrogates radiation induced pulmonary
      inflammation.
AB  - Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is
      induced by exposure to ionizing radiation. The lung was used as a model to study
      the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like
      response. ICAM-1 expression increased in the pulmonary microvascular endothelium
      and not in the endothelium of larger pulmonary vessels following treatment of
      mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression,
      we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody
      labeling of pulmonary microvascular endothelial cells from human cadaver donors
      (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify
      the fluorescence intensity of ICAM in the irradiated lung. These studies showed a
      dose- and time-dependent increase in ICAM-1 expression in the pulmonary
      microvascular endothelium. Peak expression occurred at 24 h, while threshold dose
      was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell
      infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was
      administered by tail vein injection to mice following thoracic irradiation.
      Inflammatory cells were quantified by immunofluorescence for leukocyte common
      antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed
      attenuation of inflammatory cell infiltration into the lung in response to
      ionizing radiation exposure. To verify the requirement of ICAM-1 in the
      inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM
      1 was not expressed in the lungs of ICAM-1-deficient mice following treatment
      with thoracic irradiation. ICAM-1 knockout mice had no increase in the
      inflammatory cell infiltration into the lung in response to thoracic irradiation.
      These studies demonstrate a radiation dose-dependent increase in ICAM-1
      expression in the pulmonary microvascular endothelium, and show that ICAM-1 is
      required for inflammatory cell infiltration into the irradiated lung.

PMID- 9177237
TI  - Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant
      alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of
      TPMT activity.
AB  - TPMT is a cytosolic enzyme that catalyzes the S-methylation of aromatic and
      heterocyclic sulfhydryl compounds, including medications such as mercaptopurine
      and thioguanine. TPMT activity exhibits autosomal codominant genetic
      polymorphism, and patients inheriting TPMT deficiency are at high risk of
      potentially fatal hematopoietic toxicity. The most prevalent mutant alleles
      associated with TPMT deficiency in humans have been cloned and characterized
      (TPMT*2 and TPMT*3A), but the mechanisms for loss of catalytic activity have not
      been elucidated. In the present study, we established that erythrocyte TPMT
      activity was significantly related to the amount of TPMT protein on Western blots
      of erythrocytes from patients with TPMT activities of 0.4-23 units/ml pRBC (rs =
      0.99; P < 0.001). Similarly, heterologous expression of wild-type (TPMT*1) and
      mutant (TPMT*2 and TPMT*3A) human cDNAs in yeast and COS-1 cells demonstrated
      comparable levels of TPMT mRNA but significantly lower TPMT protein with the
      mutant cDNAs. Rates of protein synthesis were comparable for wild-type and mutant
      proteins expressed in yeast and with in vitro translation in rabbit reticulocyte
      lysates. In contrast, pulse-chase experiments revealed significantly shorter
      degradation half-lives for TPMT*2 and TPMT*3A ( approximately 0.25 hr) compared
      with wild-type TPMT*1 (18 hr). The degradation of mutant proteins was impaired by
      ATP depletion and in yeast with mutant proteasomes (pre-1 strain) but unaffected
      by the lysosomal inhibitor chloroquine. These studies establish enhanced
      degradation of TPMT proteins encoded by TPMT*2 and TPMT*3A as mechanisms for
      lower TPMT protein and catalytic activity inherited by the predominant mutant
      alleles at the human TPMT locus.

PMID- 9177236
TI  - A role for Sp and nuclear receptor transcription factors in a cardiac
      hypertrophic growth program.
AB  - During cardiac hypertrophy, the chief myocardial energy source switches from
      fatty acid beta-oxidation (FAO) to glycolysis-a reversion to fetal metabolism.
      The expression of genes encoding myocardial FAO enzymes was delineated in a
      murine ventricular pressure overload preparation to characterize the molecular
      regulatory events involved in the alteration of energy substrate utilization
      during cardiac hypertrophy. Expression of genes involved in the
      thioesterification, mitochondrial import, and beta-oxidation of fatty acids was
      coordinately down-regulated after 7 days of right ventricular (RV) pressure
      overload. Results of RV pressure overload studies in mice transgenic for the
      promoter region of the gene encoding human medium-chain acyl-CoA dehydrogenase
      (MCAD, which catalyzes a rate-limiting step in the FAO cycle) fused to a
      chloramphenicol acetyltransferase reporter confirmed that repression of MCAD gene
      expression in the hypertrophied ventricle occurred at the transcriptional level.
      Electrophoretic mobility-shift assays performed with MCAD promoter fragments and
      nuclear protein extracts prepared from hypertrophied and control RV identified
      pressure overload-induced protein/DNA interactions at a regulatory unit shown
      previously to confer control of MCAD gene transcription during cardiac
      development. Antibody "supershift" studies demonstrated that members of the Sp
      (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter
      transcription factor (COUP-TF)/erbA-related protein 3] families interact with the
      pressure overload-responsive unit. Cardiomyocyte transfection studies confirmed
      that COUP-TF repressed the transcriptional activity of the MCAD promoter. The DNA
      binding activities and nuclear expression of Sp1/3 and COUP-TF in normal fetal
      mouse heart were similar to those in the hypertrophied adult heart. These results
      identify a transcriptional regulatory mechanism involved in the reinduction of a
      fetal metabolic program during pressure overload-induced cardiac hypertrophy.

PMID- 9177238
TI  - Safety-modified episomal vectors for human gene therapy.
AB  - The effectiveness of ongoing gene therapy trials may be limited by the expression
      characteristics of viral and plasmid-based vectors. To enhance levels of
      heterologous gene expression, we have developed a safety-modified episomal
      expression vector that replicates extrachromosomally in human cells. This vector
      system employs a simian virus 40 (SV40) large T antigen mutant (107/402-T) that
      is deficient in binding to human tumor suppressor gene products, including p53,
      retinoblastoma, and p107, yet retains replication competence. These SV40-based
      episomes replicate to thousands of copies by 2-4 days after gene transfer in
      multiple types of human cell lines, with lower activity in hamster cells, and no
      detectable activity in dog, rat, and murine cell lines. Importantly, 107/402-T
      has enhanced replication activity compared with wild-type T antigen; this finding
      may be due, in part, to the inability of p53 and retinoblastoma to inactivate
      107/402-T function. We demonstrate that the level and duration of 107/402-T
      expression regulates the observed episomal copy number per cell. Compared with
      standard plasmid constructs, episomes encoding 107/402-T yield approximately 10-
      to 100-fold enhanced levels of gene expression in unselected populations of
      transient transfectants. To determine if 107/402-T-based episomes replicate
      extrachromosomally in vivo, tumor explants in nude mice were directly injected
      with liposome/DNA complexes. Using a PCR-based assay, we demonstrate that SV40
      based episomes replicate in human cells after direct in vivo gene transfer. These
      data suggest that safety-modified SV40-based episomes will be effective for
      cancer gene therapy because high level expression of therapeutic genes in
      transient transfectants should yield enhanced tumor elimination.

PMID- 9177239
TI  - Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin
      deficiency and resistance.
AB  - Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share
      sequence similarity with the receptor for leptin, an adipocyte-derived cytokine
      involved in body weight homeostasis. We report here that CNTF and leptin activate
      a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF
      receptor subunits, similarly to the mRNA of leptin receptor, are localized in
      mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic
      administration of CNTF or leptin led to rapid induction of the tis-11 primary
      response gene in the arcuate nucleus, suggesting that both cytokines can signal
      to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of
      ob/ob mice, which lack functional leptin, was found to reduce the adiposity,
      hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike
      leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack
      functional leptin receptor, and in mice with diet-induced obesity, which are
      partially resistant to the actions of leptin. The identification of a cytokine
      mediated anti-obesity mechanism that acts independently of the leptin system may
      help to develop strategies for the treatment of obesity associated with leptin
      resistance.

PMID- 9177241
TI  - Frequency-domain techniques enhance optical mammography: initial clinical
      results.
AB  - We present a novel approach to optical mammography and initial clinical results.
      We have designed and developed a frequency-domain (110-MHz) optical scanner that
      performs a transillumination raster scan of the female breast in approximately 3
      min. The probing light is a dual-wavelength (690 and 810 nm, 10-mW average
      power), 2-mm-diameter laser beam, and the detection optical fiber is 5 mm in
      diameter. The ac amplitude and phase data are processed with use of an algorithm
      that performs edge effect corrections, thereby enhancing image contrast. This
      contrast enhancement results in a greater tumor detectability compared with
      simple light intensity images. The optical mammograms are displayed on a computer
      screen in real time. We present x-ray and optical mammograms from two patients
      with breast tumors. Our initial clinical results show that the frequency-domain
      scanner, even at the present stage of development, has the potential to be a
      useful tool in mammography.

PMID- 9177240
TI  - CCAAT/enhancer binding protein epsilon is preferentially up-regulated during
      granulocytic differentiation and its functional versatility is determined by
      alternative use of promoters and differential splicing.
AB  - CCAAT/enhancer binding protein (C/EBP) epsilon is a recently cloned member of the
      C/EBP family of transcription factors and is expressed exclusively in cells of
      hematopoietic origin. The human C/EBPepsilon gene is transcribed by two
      alternative promoters, Palpha and Pbeta. A combination of differential splicing
      and alternative use of promoters generates four mRNA isoforms, of 2.6 kb and 1.3
      1.5 kb in size. These transcripts can encode three proteins of calculated
      molecular mass 32.2 kDa, 27.8 kDa, and 14.3 kDa. Accordingly, Western blots with
      antibodies specific for the DNA-binding domain, that is common to all forms,
      identify multiple proteins. C/EBPepsilon mRNA was greatly induced during in vitro
      granulocytic differentiation of human primary CD34(+) cells. Retinoic acid
      treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBPepsilon
      mRNA levels by 4-fold, while prolonged treatment gradually reduced mRNA
      expression to pretreatment levels. Transient transfection experiments with
      expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein
      is an activator of transcription of granulocyte colony-stimulating factor
      receptor promoter, while the 14.3-kDa protein is not. Thus, C/EBPepsilon is
      regulated in a complex fashion and may play a role in the regulation of genes
      involved in myeloid differentiation.

PMID- 9177242
TI  - Orally absorbed reactive glycation products (glycotoxins): an environmental risk
      factor in diabetic nephropathy.
AB  - Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking
      species (glycotoxins) that contribute to the vascular and renal complications of
      diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous
      AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD).
      The aim of this study was to examine the oral absorption and renal clearance
      kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs
      contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and
      five healthy subjects (NL) received a single meal of egg white (56 g protein),
      cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine
      samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA
      and for AGE-specific crosslinking reactivity, based on complex formation with
      125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct
      elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8,
      P < 0.05): the area under the curve for serum ( approximately 10% of ingested
      AGE) correlated directly with severity of KD; renal excretion of dietary AGE,
      although normally incomplete (only approximately 30% of amount absorbed), in DM
      it correlated inversely with degree of albuminuria, and directly with creatinine
      clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE
      meal serum exhibited increased AGE-crosslinking activity (two times above
      baseline serum AGE, three times above negative control), which was inhibited by
      aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is
      markedly suppressed in diabetic nephropathy patients, (ii) daily influx of
      dietary AGEs includes glycotoxins that may constitute an added chronic risk for
      renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may
      greatly reduce the burden of AGEs in diabetic patients and possibly improve
      prognosis.

PMID- 9177243
TI  - D-Ala-D-Ala ligases from glycopeptide antibiotic-producing organisms are highly
      homologous to the enterococcal vancomycin-resistance ligases VanA and VanB.
AB  - The crisis in antibiotic resistance has resulted in an increasing fear of the
      emergence of untreatable organisms. Resistance to the glycopeptide antibiotic
      vancomycin in the enterococci, and the spread of these pathogens throughout the
      environment, has shown that this scenario is a matter of fact rather than
      fiction. The basis for vancomycin resistance is the manufacture of the
      depsipeptide D-Ala-D-lactate, which is incorporated into the peptidoglycan cell
      wall in place of the vancomycin target D-Ala-D-Ala. Pivotal to the resistance
      mechanism is the production of a D-Ala-D-Ala ligase capable of ester formation.
      Two highly efficient depsipeptide ligases have been cloned from vancomycin
      resistant enterococci: VanA and VanB. These ligases show high amino acid sequence
      similarity to each other ( approximately 75%), but less so to other D-Ala-D-X
      ligases (<30%). We have cloned ddls from two glycopeptide-producing organisms,
      the vancomycin producer Amycolatopsis orientalis and the A47934 producer
      Streptomyces toyocaensis. These ligases show strong predicted amino acid homology
      to VanA and VanB (>60%) but not to other D-Ala-D-X ligases (<35%). The D-Ala-D
      Ala ligase from S. toyocaensis shows D-Ala-D-lactate synthase activity in cell
      free extracts of S. lividans transformed with the ddl gene and confirms the
      predicted enzymatic activity. These results imply a close evolutionary
      relationship between resistance mechanisms in the clinics and in drug-producing
      bacteria.

PMID- 9177244
TI  - A cluster of bacterial genes for anaerobic benzene ring biodegradation.
AB  - A reductive benzoate pathway is the central conduit for the anaerobic
      biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction
      requires a large input of energy and this metabolic capability has, so far, been
      reported only in bacteria. To determine the molecular basis for this
      environmentally important process, we cloned and analyzed genes required for the
      anaerobic degradation of benzoate and related compounds from the phototrophic
      bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that
      includes twelve genes likely to be involved in anaerobic benzoate degradation and
      additional genes that convert the related compounds 4-hydroxybenzoate and
      cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a
      novel enzyme able to overcome the resonance stability of the aromatic ring, were
      identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2
      ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic
      activity of the protein expressed in Escherichia coli. Physiological data and DNA
      sequence analyses indicate that the benzoate pathway consists of unusual enzymes
      for ring reduction and cleavage interposed among enzymes homologous to those
      catalyzing fatty acid degradation. The cloned genes should be useful as probes to
      identify benzoate degradation genes from other metabolically distinct groups of
      anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.

PMID- 9177245
TI  - Agonist-induced closure of constitutively open gamma-aminobutyric acid channels
      with mutated M2 domains.
AB  - Ligand-gated ion channels display a fundamental property-channels remain
      virtually closed at rest and open upon agonist binding. Here we show that
      substituting alanines for either of two amino acid residues (T314 or L317) in the
      M2 region of the gamma-aminobutyric acid (GABA) rho1 subunit results in
      spontaneous channel opening in the absence of ligand. Surprisingly, for two
      single point mutants (T314A or L317A), application of very low concentrations of
      agonist partially suppressed this spontaneous current, while higher
      concentrations re-activated the receptors. When both of these sites were mutated
      (T314A/L317A), GABA nearly completely suppressed the constitutive current and did
      not re-activate the current even at very high concentrations. This study provides
      important new insights into the structure-function relationship of ligand-gated
      ion channels, where modification of the structure of the channel pore region not
      only alters the allosteric transition of the receptor protein but also reverses
      the polarity of agonist regulation of channel gating. Our results suggest that
      the sites where these two residues are located are structurally critical for
      channel gating.

PMID- 9177246
TI  - Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67
      kDa isoform of glutamic acid decarboxylase.
AB  - In addition to its role as an inhibitory neurotransmitter, gamma-aminobutyric
      acid (GABA) is presumed to be involved in the development and plasticity of the
      nervous system. GABA is synthesized by glutamic acid decarboxylase (GAD), but the
      respective roles of its two isoforms (GAD65 and 67) have not been determined. The
      selective elimination of each GAD isoform by gene targeting is expected to
      clarify these issues. Recently we have produced GAD65 -/- mice and demonstrated
      that lack of GAD65 does not change brain GABA contents or animal behavior, except
      for a slight increase in susceptibility to seizures. Here we report the
      production of GAD67 -/- mice. These mice were born at the expected frequency but
      died of severe cleft palate during the first morning after birth. GAD activities
      and GABA contents were reduced to 20% and 7%, respectively, in the cerebral
      cortex of the newborn GAD67 -/- mice. Their brain, however, did not show any
      discernible defects. Previous pharmacological and genetic investigations have
      suggested the involvement of GABA in palate formation, but this is the first
      demonstration of a role for GAD67-derived GABA in the development of nonneural
      tissue.

PMID- 9177247
TI  - Spreading depression and focal brain ischemia induce cyclooxygenase-2 in cortical
      neurons through N-methyl-D-aspartic acid-receptors and phospholipase A2.
AB  - Repetitive spreading depression (SD) waves, involving depolarization of neurons
      and astrocytes and up-regulation of glucose consumption, is thought to lower the
      threshold of neuronal death during and immediately after ischemia. Using rat
      models for SD and focal ischemia we investigated the expression of cyclooxygenase
      1 (COX-1), the constitutive form, and cyclooxygenase-2 (COX-2), the inducible
      form of a key enzyme in prostaglandin biosynthesis and the target enzymes for
      nonsteroidal anti-inflammatory drugs. Whereas COX-1 mRNA levels were undetectable
      and uninducible, COX-2 mRNA and protein levels were rapidly increased in the
      cortex, especially in layers 2 and 3 after SD and transient focal ischemia. The
      cortical induction was reduced by MK-801, an N-methyl-D-aspartic acid-receptor
      antagonist, and by dexamethasone and quinacrine, phospholipase A2 (PLA2)
      inhibiting compounds. MK-801 acted by blocking SD whereas treatment with PLA2
      inhibitors preserved the wave propagation. NBQX, an alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid/kainate-receptor antagonist, did not affect the
      SD-induced COX-2 expression, whereas COX-inhibitors indomethacin and diclofenac,
      as well as a NO synthase-inhibitor, NG-nitro-L-arginine methyl ester, tended to
      enhance the COX-2 mRNA expression. In addition, ischemia induced COX-2 expression
      in the hippocampal and perifocal striatal neurons and in endothelial cells. Thus,
      COX-2 is transiently induced after SD and focal ischemia by activation of N
      methyl-D-aspartic acid-receptors and PLA2, most prominently in cortical neurons
      that are at a high risk to die after focal brain ischemia.

PMID- 9177248
TI  - A nonrandom dynamic component in the synaptic noise of a central neuron.
AB  - Continuous segments of synaptic noise were recorded in vivo from teleost Mauthner
      cells and were studied with the methods of nonlinear analysis. As in many central
      neurons, this ongoing activity is dominated by consecutive inhibitory
      postsynaptic potentials. Recurrence plots and first or third order Poincare maps
      combined with surrogate shuffling revealed nonrandom patterns consistent with the
      notion that synaptic noise is a continuously varying mixture of periodic and
      chaotic phases. Chaos was further demonstrated by the occurrence of unstable
      periodic orbits. The nonrandom component of the noise is reproducibly and
      persistently reduced when the level of background sound, a natural stimulus for
      networks afferent to the Mauthner cell, is briefly elevated. These data are
      consistent with a model involving a reciprocally connected inhibitory network,
      presynaptic to the Mauthner cell and its intrinsic properties. The presence of
      chaos in the inhibitory synaptic noise that regulates the excitability of the
      Mauthner cell and its sensitivity to external stimuli suggests that it modulates
      this neuron's function, namely to trigger a fast escape motor reaction following
      unexpected sensory information.

PMID- 9177249
TI  - Cholinergic stimulation alters performance and task-specific regional cerebral
      blood flow during working memory.
AB  - Modulation of the cholinergic neurotransmitter system results in changes in
      memory performance, including working memory (WM), in animals and in patients
      with Alzheimer disease. To identify associated changes in the functional brain
      response, we studied performance measures and regional cerebral blood flow (rCBF)
      using positron emission tomography (PET) in healthy subjects during performance
      of a WM task. Eight control subjects received an infusion of saline throughout
      the study and 13 experimental subjects received a saline infusion for the first 2
      scans followed by a continuous infusion of physostigmine, an acetylcholinesterase
      inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a
      sequence of 10 PET scans that alternated between rest and task scans. During task
      scans, subjects performed the WM task for faces. Physostigmine both improved WM
      efficiency, as indicated by faster reaction times, and reduced WM task-related
      activity in anterior and posterior regions of right midfrontal gyrus, a region
      shown previously to be associated with WM. Furthermore, the magnitudes of
      physostigmine-induced change in reaction time and right midfrontal rCBF
      correlated. These results suggest that enhancement of cholinergic function can
      improve processing efficiency and thus reduce the effort required to perform a WM
      task, and that activation of right prefrontal cortex is associated with task
      effort.

PMID- 9177250
TI  - The perception of transparent three-dimensional objects.
AB  - When the proximal and distal elements of wire-frame cubes are conflated,
      observers perceive illusory structures that no longer behave veridically. These
      phenomena suggest that what we normally see depends on visual associations
      generated by experience. The necessity of such learning may explain why the
      mammalian visual system is subject to a prolonged period of plasticity in early
      life, when novel circuits are made in enormous numbers.

PMID- 9177251
TI  - Cell-surface perturbations of the epidermal growth factor and vascular
      endothelial growth factor receptors by phosphorothioate oligodeoxynucleotides.
AB  - Antisense oligodeoxynucleotides offer potential as therapeutic agents to inhibit
      gene expression. Recent evidence indicates that oligodeoxynucleotides designed to
      target specific nucleic acid sequences can interact nonspecifically with
      proteins. This report describes the interactive capabilities of phosphorothioate
      oligodeoxynucleotides of defined sequence and length with two essential protein
      tyrosine receptors, flk-1 and epidermal growth factor receptor (EGFR), and their
      effects on receptor signaling in a transfected and tumor cell line, respectively.
      Phosphorothioate oligodeoxynucleotides bound to the cell surface, as demonstrated
      by fluorescence-activated cell-sorter analyses (FACS), and perturbed receptor
      activation in the presence and absence of cognate ligands, EGF (EGFR) and
      vascular endothelial growth factor (flk-1), in phosphorylation assays. Certain
      phosphorothioate oligodeoxynucleotides interacted relatively selectively with flk
      1 and partially blocked the binding of specific anti-receptor monoclonal
      antibodies to target sites. They stimulated EGFR phosphorylation in the absence
      of EGF but antagonized ligand-mediated activation of EGFR and flk-1. In vivo
      studies showed that a nonspecific phosphorothioate oligodeoxynucleotide
      suppressed the growth of glioblastoma in a mouse model of tumorigenesis. These
      results emphasize the capacity of phosphorothioate oligodeoxynucleotides to
      interact with cells in a sequence-selective nonantisense manner, while
      associating with cellular membrane proteins in ways that can inhibit cellular
      metabolic activities.

PMID- 9177252
TI  - Elevation of intracellular calcium in smooth muscle causes endothelial cell
      generation of NO in arterioles.
AB  - It is well known that vascular smooth muscle tone can be modulated by signals
      arising in the endothelium (e.g., endothelium-derived relaxing factor,
      endothelium-derived hyperpolarizing factor, and prostaglandins). Here we show
      that during vasoconstriction a signal can originate in smooth muscle cells and
      act on the endothelium to cause synthesis of endothelium-derived relaxing factor.
      We studied responses to two vasoconstrictors (phenylephrine and KCl) that act by
      initiating a rise in smooth muscle cell intracellular Ca2+ concentration
      ([Ca2+]i) and exert little or no direct effect on the endothelium. Fluo-3 was
      used as a Ca2+ indicator in either smooth muscle or endothelial cells of
      arterioles from the hamster cheek pouch. Phenylephrine and KCl caused the
      expected rise in smooth muscle cell [Ca2+]i that was accompanied by an elevation
      in endothelial cell [Ca2+]i. The rise in endothelial cell [Ca2+]i was followed by
      increased synthesis of NO, as evidenced by an enhancement of the vasoconstriction
      induced by both agents after blockade of NO synthesis. The molecule involved in
      signal transmission from smooth muscle to endothelium is as yet unknown. However,
      given that myoendothelial cell junctions are frequent in these vessels, we
      hypothesize that the rise in smooth muscle cell Ca2+ generates a diffusion
      gradient that drives Ca2+ through myoendothelial cell junctions and into the
      endothelial cells, thereby initiating the synthesis of NO.

PMID- 9177253
TI  - Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine
      epithelium.
AB  - Estradiol-17beta (E2) acts through the estrogen receptor (ER) to regulate uterine
      growth and functional differentiation. To determine whether E2 elicits epithelial
      mitogenesis through epithelial ER versus indirectly via ER-positive stromal
      cells, uteri from adult ER-deficient ER knockout (ko) mice and neonatal ER
      positive wild-type (wt) BALB/c mice were used to produce the following tissue
      recombinants containing ER in epithelium (E) and/or stroma (S), or lacking ER
      altogether: wt-S + wt-E, wt-S + ko-E, ko-S + ko-E, and ko-S + wt-E. Tissue
      recombinants were grown for 4 weeks as subrenal capsule grafts in intact female
      nude mice, then the hosts were treated with either E2 or oil a week after
      ovariectomy. Epithelial labeling index and ER expression were determined by
      [3H]thymidine autoradiography and immunohistochemistry, respectively. In tissue
      recombinants containing wt-S (wt-S + wt-E, wt-S + ko-E), E2 induced a similar
      large increase in epithelial labeling index compared with oil-treated controls in
      both types of tissue recombinants despite the absence of epithelial ER in wt-S +
      ko-E tissue recombinants. This proliferative effect was blocked by an ER
      antagonist, indicating it was mediated through ER. In contrast, in tissue
      recombinants prepared with ko-S (ko-S + ko-E and ko-S + wt-E), epithelial
      labeling index was low and not stimulated by E2 despite epithelial ER expression
      in ko-S + wt-E grafts. In conclusion, these data demonstrate that epithelial ER
      is neither necessary nor sufficient for E2-induced uterine epithelial
      proliferation. Instead, E2 induction of epithelial proliferation appears to be a
      paracrine event mediated by ER-positive stroma. These data in the uterus and
      similar studies in the prostate suggest that epithelial mitogenesis in both
      estrogen and androgen target organs are stromally mediated events.

PMID- 9177254
TI  - Transgenic A1 adenosine receptor overexpression increases myocardial resistance
      to ischemia.
AB  - Activation of myocardial A1 adenosine receptors (A1AR) protects the heart from
      ischemic injury. In this study transgenic mice were created using the cardiac
      specific alpha-myosin heavy chain promoter and rat A1AR cDNA. Heart membranes
      from two transgene positive lines displayed approximately 1,000-fold
      overexpression of A1AR (6,574 +/- 965 and 10,691 +/- 1,002 fmol per mg of protein
      vs. 8 +/- 5 fmol per mg of protein in control hearts). Compared with control
      hearts, transgenic Langendorff-perfused hearts had a significantly lower
      intrinsic heart rate (248 beats per min vs. 318 beats per min, P < 0. 05), lower
      developed tension (1.2 g vs. 1.6 g, P < 0.05), and similar coronary resistance.
      The difference in developed tension was eliminated by pacing. Injury of control
      hearts during global ischemia, indexed by time-to-ischemic contracture, was
      accelerated by blocking adenosine receptors with 50 microM 8-(p-sulfophenyl)
      theophylline but was unaffected by addition of 20 nM N6-cyclopentyladenosine, an
      A1AR agonist. Thus A1ARs in ischemic myocardium are presumably saturated by
      endogenous adenosine. Overexpressing myocardial A1ARs increased time-to-ischemic
      contracture and improved functional recovery during reperfusion. The data
      indicate that A1AR activation by endogenous adenosine affords protection during
      ischemia, but that the response is limited by A1AR number in murine myocardium.
      Overexpression of A1AR affords additional protection. These data support the
      concept that genetic manipulation of A1AR expression may improve myocardial
      tolerance to ischemia.

PMID- 9177256
TI  - Cloning gibberellin dioxygenase genes from pumpkin endosperm by heterologous
      expression of enzyme activities in Escherichia coli.
AB  - Gibberellin (GA) plant hormones are biosynthesized via complex pathways, the
      final steps of which are catalyzed by 2-oxoglutarate-dependent dioxygenases.
      Here, the cloning of two such enzymes, the GA 7-oxidase and the GA 20-oxidase, is
      reported using a novel approach, namely, by screening for GA dioxygenase
      activities expressed as T7 gene 10 fusion proteins in recombinant Escherichia
      coli. In vitro translation products of mRNA from endosperm of immature pumpkin
      seeds contained three GA dioxygenase activities, including 7-oxidase, 20-oxidase,
      and 3beta-hydroxylase. A cDNA expression library was prepared from the endosperm
      mRNA in lambdaMOSElox. An aliquot of the amplified library was converted to
      plasmids in vivo and used for transformation of E. coli BL21(DE3), which
      thereafter expressed recombinant fusion proteins containing 7-oxidase, 20
      oxidase, and 3beta-hydroxylase activities. By screening for specific GA
      dioxygenase expression, clones harboring 7-oxidase and 20-oxidase cDNA were
      isolated. The ORF of the 7-oxidase cDNA is 945 bp long, encoding for 314 amino
      acid residues with a calculated Mr of 35,712 and pI of 5.7. Recombinant GA 7
      oxidase oxidizes GA12-aldehyde to GA12 and GA14-aldehyde to GA14. Evidence was
      obtained for further metabolism of GA12 by the 7-oxidase to four products, two of
      which are monohydroxylated GA12. The ORF of the 20-oxidase is-apart from seven
      changes, resulting in four amino acid substitutions-identical to the 20-oxidase
      cDNA previously cloned from pumpkin cotyledon mRNA; both 20-oxidases have the
      same catalytic properties.

PMID- 9177257
TI  - Group I allergens of grass pollen as cell wall-loosening agents.
AB  - Group I allergens are the major allergens of grass pollen, but their biological
      function is unknown. These proteins are shown here to be structurally related to
      expansins, which are able to induce extension (creep) of plant cell walls.
      Extracts of maize pollen possess potent expansin-like activity, as measured in
      wall extension and wall stress-relaxation assays. This activity is selective for
      grass cell walls and is, at least partly, due to the action of maize group I
      allergens. We propose that group I allergens facilitate invasion of the pollen
      tube into the maternal tissues by loosening the cell walls of the grass stigma
      and style. Additionally, the presence of related mRNAs in vegetative tissues of
      rice, Arabidopsis, and soybean implies that allergen homologs may function to
      loosen walls in growing vegetative tissues as well.

PMID- 9177260
TI  - Oxidative stress increases hepatocyte iNOS gene transcription and promoter
      activity.
AB  - Hepatocyte expression of inducible nitric oxide synthase (iNOS) is initiated by
      the presence of pro-inflammatory cytokines, such as interleukin-1beta (IL-1). In
      the presence of oxidative stress, IL-1beta mediated hepatocyte iNOS expression
      and NO synthesis are significantly increased. To determine the underlying
      molecular mechanism responsible for oxidative stress augmentation of hepatocyte
      iNOS expression, rat hepatocytes in primary culture were stimulated with IL-1beta
      (250 U/mL) in the presence and absence of benzenetriol (BZT, 0-100 microM), an
      autocatalytic source of superoxide at physiologic pH. Nuclear runon analysis
      demonstrated that BZT was associated with increased iNOS gene transcription in
      the setting of IL-1 stimulation. Transient transfection of a plasmid construct
      composed of the rat hepatocyte iNOS promoter and a chloramphenicol transferase
      reporter gene demonstrated that the combination of BZT and IL-1 significantly
      increased iNOS promoter activity in comparison to that of IL-1beta alone. These
      data indicate that BZT-mediated oxidative stress increases IL-1beta induced iNOS
      gene transcription and iNOS promoter activity.

PMID- 9177259
TI  - Vaccination against colonizing bacteria with multiple serotypes.
AB  - Conjugate vaccines protect vaccinated individuals against both disease from and
      nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae.
      Protection is specific to the capsular serotype(s) included in the vaccine. This
      specificity has raised concern that vaccination against particular ("targeted")
      serotypes may cause an increase in carriage of (and diseases attributable to)
      nontargeted serotypes. I analyzed a mathematical model designed to predict the
      factors affecting, and the expected extent of, such replacement in the host
      population. The conditions for competitive exclusion and coexistence of serotypes
      under mass vaccination are derived, and the equilibrium carriage of target and
      nontarget serotypes is determined under various ecological and epidemiological
      conditions. The eradication threshold for a target serotype in the presence of
      competing, nontarget serotypes is always lower for serotype-specific than for
      bivalent vaccines. In a two-serotype model, the increase in the prevalence of any
      single nontargeted serotype due to vaccination will not exceed the total
      reduction in prevalence of a targeted serotype. However, if three or more
      serotypes interact epidemiologically, vaccination against one type may increase
      carriage of a second more than it decreases carriage of the first. Carriage of a
      second serotype against which the vaccine offers only partial protection may
      initially increase and then decrease as a function of vaccine coverage. I discuss
      the extent to which these theoretical results can account for existing data on
      serotype replacement after vaccination against H. influenzae and their
      implications for vaccine policy.

PMID- 9177261
TI  - Thioredoxin reductase activity is decreased by selenium deficiency.
AB  - Animal thioredoxin reductase is a selenoprotein. In this study, thioredoxin
      reductase activities in liver, kidney, and brain have been compared in rats fed
      selenium-deficient and control diets for 14 weeks following weaning. Selenium
      deficiency caused a decrease in thioredoxin reductase activity from control to
      4.5% in liver and 11% in kidney. However, brain thioredoxin reductase activity
      was not affected by selenium deficiency of this severity. Gold inhibited
      thioredoxin reductase activity in the liver in a manner typical of its effect on
      selenoenzymes. Repletion of selenium-deficient rats with injections of selenium
      caused thioredoxin reductase activity to increase more rapidly in the liver than
      glutathione peroxidase activity but more slowly than selenoprotein P. These
      results indicate that thioredoxin reductase activity in liver and kidney is
      sensitive to selenium nutritional status but that brain thioredoxin reductase
      activity is less sensitive.

PMID- 9177262
TI  - Activities of vitamin Q10 in animal models and a serious deficiency in patients
      with cancer.
AB  - New data on blood levels of vitamin Q10 in 116 cancer patients reveal an
      incidence of 23.1% of patients (N=17) with breast cancer whose blood levels were
      below 0.5 microg/ml. The incidence of breast cancer cases with levels below 0.6
      microg/ml was 38.5%. The incidence is higher (p<0.05) than that for a group of
      ordinary people. Patients (N=15) with myeloma showed a mean blood level of 0.67
      +/- 0.17 microg/ml. The incidence of a vitamin Q10 blood level below 0.7
      microg/ml for these 15 cases of myeloma was 53.3%, which is higher (p<0.05) than
      the 24.5% found for a group of ordinary people.

PMID- 9177263
TI  - In vitro transcriptional activation of p21 promoter by p53.
AB  - The tumor suppressor p53 can control cell growth by inducing cell cycle arrest.
      This is effected, at least in part, by transcriptional activation of p21 gene, a
      cell cycle inhibitor. Here in vitro transcription assay for p21 has been
      established. The assay recapitulates activation of p21 promoter mediated by p53
      in vitro. Thus this in vitro assay will allow to study how transcriptional
      regulation of p21 can be linked to cell cycle controls during development and
      neoplastic transformation processes.

PMID- 9177264
TI  - Shift of DNA polymerase alpha nuclear distribution and activity in apoptotic
      human leukaemia cells.
AB  - The changes in the distribution of DNA polymerase alpha in nuclei from HL-60
      cells treated with Methotrexate (MTX) for up to 15 hr. were checked by means of
      both confocal analysis and electron microscopy analysis. The results provided
      evidence that, relative to controls, in the MTX treated cells the enzyme
      undergoes a topographical rearrangement throughout the nucleus, showing a pattern
      of distribution which calls to mind the nuclear matrix structure. The "in vitro"
      analysis of DNA polymerases alpha, beta, and gamma activities revealed that, in
      nuclei from control cells, DNA polymerase alpha was the principal DNA polymerase
      driving this "in vitro" system, while after 15 hr. of MTX treatment its activity
      was largely decreased and replaced by DNA polymerase beta, which is believed to
      be associated with DNA repair. Taken together, these results suggest that among
      the intracellular processes elicited by MTX-induced apoptosis in HL60 cells, the
      redistribution of DNA polymerase alpha and the stimulation of DNA polymerase beta
      activity might represent an extreme attempt of the cell to preserve the
      replicative machinery during fragmentation and chromatin margination.

PMID- 9177265
TI  - [Tyr1]-nociceptin, a novel nociceptin analog, decreases systemic arterial
      pressure by a naloxone-insensitive mechanism in the rat.
AB  - The heptadecapeptide nociceptin, also known as Orphanin FQ, is a newly discovered
      endogenous ligand for the opioid-like G-protein-coupled receptor ORL1. In the
      present study, responses to a novel nociceptin analog, [Tyr1]-nociceptin, were
      investigated in the systemic vascular bed of the rat. [Tyr1]-nociceptin induced
      dose-related decrease in systemic arterial pressure when injected in doses of 1
      30 nmol/kg i.v. In terms of relative vasodepressor activity, [Tyr1]-nociceptin
      was comparable in potency to nociceptin. The decreases in systemic arterial
      pressure in response to [Tyr1]-nociceptin were not altered by the opioid receptor
      antagonist naloxone in a dose that reduced responses to Met-enkephalin. The
      results of the present study show that vasodepressor responses to [Tyr1]
      nociceptin are not mediated by the activation of a naloxone-sensitive opioid
      receptor and are not dependent on the presence of Phe at the N-terminus of the
      nociceptin sequence.

PMID- 9177266
TI  - An NADH-dependent disulfide reductase activity in the endoplasmic reticulum of
      Dictyostelium discoideum.
AB  - A novel disulfide reductase activity was observed in the amoeba, Dictyostelium
      discoideum. Both 5,5'-dithiobis(2-nitro-benzoate) (DTNB) and insulin were
      substrates for reduction. NADH was utilized in preference to NADPH. The activity
      comigrated with NADPH-dependent cytochrome c reductase on sucrose gradients,
      suggesting localization in the endoplasmic reticulum (ER). The buoyant density of
      the disulfide reductase was not shifted when ribosomes were released from the ER
      nor was the activity solubilized when membranes were shocked with low osmotic
      buffer. It therefore appears that the reductase was membrane-bound in the lumen
      of the smooth ER.

PMID- 9177267
TI  - Differential splicing of the GTP cyclohydrolase I RNA in dopa-responsive
      dystonia.
AB  - We characterized the GTP cyclohydrolase I (GTP-CH-I) gene in a patient with
      hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive
      dystonia (HPD/DRD). The sequence analysis revealed a C to A transversion, which
      predicts a novel missense mutation (Thr186Lys). Unexpectedly, this base change,
      occurring in the middle of exon 5, resulted in a production of the novel
      transcript lacking exon 5 and a part of exon 6. Three different transcripts of
      the GTP-CH-I gene, previously reported in the human liver, were also present in
      the peripheral lymphocytes from the patient and controls. Quantitative comparison
      of the truncated-subunit mRNA and the wild-type one implied that differential
      splicing regulates the GTP-CH-I enzyme activity, leading to the clinical
      variations in HPD/DRD. The patient showed a unique clinical symptom, suggesting
      that the nigrostriatal dopaminergic system is more affected than previously
      thought in HPD/DRD.

PMID- 9177268
TI  - Expression, purification, and characterization of human cAMP-specific
      phosphodiesterase (PDE4) subtypes A, B, C, and D.
AB  - Although four members (A, B, C, and D) of the cAMP-specific phosphodiesterase
      (PDE4) family have been cloned by different groups, no study comparing the
      characteristics of purified human PDE4 subtypes has been published. In this
      study, we have expressed human PDE4 A, B, C, and D in insect (SF9) cells by using
      the baculovirus expression system, purified the expressed proteins, and compared
      their characteristics. The recombinant PDE4 subtypes all showed catalytic
      activity for cAMP with a K(m) of 1-5 microM. V(max) values differed significantly
      among these subtypes with the following order: C > B > A > D. PDE4 A, B, C, and D
      showed a very similar Mg2+ dependence profile. PDE4 B and C showed similar pH
      profiles with the optimal pH being 8.0. The pH profiles of PDE4 A and D were very
      different from each other and from those of B and C, with the optimal pH being
      6.5 and 7.5, respectively. Furthermore, although PDE4 A, B, C, and D were all
      inhibited by the standard PDE4 inhibitors rolipram, Ro20-1724, and etazolate, the
      inhibitory potency varied. Thus, by several criteria including kinetics, pH
      dependency, and inhibitor sensitivity, various PDE4 subtypes differ significantly
      from one another.

PMID- 9177269
TI  - Palmitylation of Src family tyrosine kinases regulates functional interaction
      with a B cell substrate.
AB  - Palmitylation of Src family tyrosine kinases has been shown to play a role in
      directing their membrane localization. Here we demonstrate that palmitylation can
      also regulate recognition and tyrosine phosphorylation of the B cell Src kinase
      substrate Ig alpha. Blk and Src, which are not palmitylated, phosphorylate co
      expressed Ig alpha in Cos cells, whereas palmitylated Src kinases do not.
      Addition of a palmitylation site to Blk abrogates its phosphorylation of the
      substrate, while mutation of Fyn's palmitylation sites results in recognition and
      phosphorylation of Ig alpha. These results indicate that palmitylation, a
      reversible protein modification, aids in regulating recognition of physiologic
      substrates by Src family tyrosine kinases.

PMID- 9177270
TI  - Mouse CD24 as a signaling molecule for integrin-mediated cell binding: functional
      and physical association with src-kinases.
AB  - CD24 is a differentiation antigen expressed by murine hematopoietic and neural
      cells which is linked to the membrane via a glycosylphosphatidylinositol (GPI)
      anchor. In monocytic ESb-MP cells the molecule serves as a ligand for P-selectin
      and triggering with CD24 specific antibodies can activate VLA-5/L1-mediated cell
      adhesion in these cells. We report here that the aggregation is specific for CD24
      and not seen with antibodies to the GPI-anchored molecule Thy-1. The Tyr-kinase
      inhibitor herbimycin can block the aggregation. We studied CD24 associated
      molecules that might be involved in signal transduction. Antibodymediated
      crosslinking of CD24 induced a rapid Tyr-phosphorylation of several cellular
      proteins in ESb-MP cells which correlated with an elevated activity of p56lck but
      not p60fyn or MAP-1 kinase. Several phosphorylated proteins were co
      immunoprecipitated with CD24. Re-immunoprecipitation allowed the detection of
      p56lck, p56hck, and p54lyn but not p60fyn, PI-3k, or PLCgamma as a compenent of
      the CD24 detergent resistant complex. It is suggested that the CD24-associated
      kinases are involved in the activation of cell aggregation.

PMID- 9177271
TI  - Cloning and characterization of Gu/RH-II binding protein.
AB  - Gu/RNA helicase II (Gu/RH-II) is the first reported mammalian nucleolar RNA
      helicase that is a member of the D-E-A-D (Asp-Glu-Ala-Asp) box family of
      proteins. It has an ATP-dependent RNA unwinding (helicase) activity and a
      separate RNA folding activity (introduction of intramolecular secondary structure
      into single-stranded RNA). To determine which proteins may bind to Gu/RH-II, a
      yeast two-hybrid system was used. A cDNA which encoded a protein, called Gu/RH-II
      binding protein or GBP, was isolated and sequenced. The GBP protein is localized
      to the nucleus in speckled or diffuse nucleoplasmic patterns. The GBP mRNA level
      is highest in testis, 9- to 49-fold greater than other tissues. When GBP
      interacts with Gu/RH-II, proteolytic cleavage of Gu/RH-II occurs; the amino
      terminal portion of Gu/RH-II is critical for this proteolysis.

PMID- 9177272
TI  - The stabilizing residues and the functional domains in the hyperthermophilic V
      ATPase of Desulfurococcus.
AB  - To clarify a universal mechanism of the intramolecular rotation of ATP-synthase,
      an operon encoding a stable, ancestral ATPase was cloned from a heterotrophic
      archaeum Desulfurococcus strain SY. The operon of about 7 kbp contained genes E,
      C, G, A, B and D encoding subunits with predicted molecular weights of 23,217,
      41,659, 11,499, 65,476, 52,295, and 24,897, respectively. The sequence was
      compared with that of Na-ATPase of Enterococcus hirae, A-ATPase of Halobacterium
      salinarium, V-ATPase of Methanosarcina mazei, and ATP synthase of Methanococcus
      jannaschii, which are homologous. (1) The cause of hyperthermostability: The main
      exchanges in the amino acid residues of hyperthermophilic proteins included Asp -
      > Glu (11 residues of A subunit of E.h.) and, Ser --> Ala. (2) The domains needed
      for the intramolecular rotation: The domains similar to those established in F
      type ATPases were also found in the V-type ATPases of species with a different
      energy metabolism.

PMID- 9177273
TI  - Clonal origin of tumor cells in a plexiform neurofibroma with LOH in NF1 intron
      38 and in dermal neurofibromas without LOH of the NF1 gene.
AB  - LOH at the NF1 locus was investigated in 38 neurofibromas of 26 NF1 patients.
      Only in one of these tumors LOH was observed. In this plexiform neurofibroma of a
      NF1 patient with a constitutional one base-pair insertion in NF1 exon 4b, a non
      random X-inactivation pattern was found, strongly suggesting a clonal origin of
      the tumor cells. The analysis of X-inactivation patterns allowed the
      classification of some of the other neurofibromas with regard to the
      detectability of clonal LOH. In 3 of 6 neurofibromas without LOH amenable to this
      analysis, a comparable X-inactivation pattern was found in constitutional and
      neurofibroma derived DNA. A clonal LOH would not have been detected in these
      tumors. However, we observed a nonrandom pattern in 3 of the 6 neurofibromas,
      suggesting a clonal origin of the tumor cells. LOH was not detected in these
      tumors, but could, however, have occurred by mutational events below the level of
      large somatic deletions, loss of a whole chromosome 17 or somatic recombination.

PMID- 9177274
TI  - Dual promoters of mouse mu-opioid receptor gene.
AB  - Two transcriptional initiation sites, distal and proximal, located at
      approximately 500 bp apart in mouse mu-opioid receptor gene were identified
      recently. Using deletional and transfection analyses, the distal or proximal
      promoter alone displayed similar activity in neuronal cells constitutively
      expressing mu-opioid receptors (SH-SY-5Y). The presence of both promoters did not
      result in an increase in activity. However, when distal promoter linked with 3'
      downstream sequences without the proximal promoter region, the distal promoter
      activity was abolished. Transfection analysis using various cell lines further
      suggested that only the proximal promoter preferentially directed the neuronal
      subtype expression. To verify the physiological importance of each promoter, the
      ratio of mu-receptor transcripts initiated by either promoter was examined by
      quantitative RT-PCR using mouse adult brain mRNA. We found that receptor mRNA was
      predominantly initiated by the proximal promoter. These studies suggested that
      the proximal promoter was the major functional promoter.

PMID- 9177275
TI  - All-aqueous, regiospecific transglycosylation synthesis of 3-O-alpha-L
      fucopyranosyl-2-acetamido-2-deoxy-D-glucopyranose, a building block for the
      synthesis of branched oligosaccharides.
AB  - A transglycosylation reaction, carried out in an aqueous medium and catalyzed by
      a crude preparation of alpha-fucosidase (E.C. 3.2.1.51) from Aspergillus niger,
      allowed for the regiospecific synthesis of the disaccharide 3-O-alpha-L
      fucopyranosyl-2-acetamido-2-deoxy-D-glucopyranose using p-nitrophenyl-alpha-L
      fucopyranose as the donor and 2-acetamido-2-deoxy-D-glucopyranose as the
      acceptor. The chemical identity of the product obtained was demonstrated by HPLC,
      ion spray mass spectrometry and NMR spectroscopy. Further transglycosylation
      using a beta-galactosidase (E.C. 3.2.1.23) yielded the branched oligosaccharide 2
      acetamido-2-deoxy-3-O-(alpha-L-fucopyranosyl)-4-O-(beta-D-galactopyran osyl)-D
      glucopyranose, i.e., the Lewis(x) antigen.

PMID- 9177276
TI  - Regulation of growth and prostatic marker expression by activin A in an androgen
      sensitive prostate cancer cell line LNCAP.
AB  - Activin A, a homodimer of the betaA subunit of inhibin, is a member of the TGF
      beta family. It is a multifunctional molecule regulating the growth,
      differentiation, and survival of a variety of cells. Treatment with activin A to
      an androgen-sensitive human prostatic cancer cell line LNCaP resulted in growth
      and morphological change and those were accompanied by up-regulation of prostatic
      differentiation markers prostate-specific antigen (PSA) and prostatic acid
      phosphatase (PAP). In addition, the expression of androgen receptor was also
      enhanced by activin treatment. These results suggest that activin has significant
      influence on LNCaP cells.

PMID- 9177277
TI  - Purification and crystallisation of the autoantigen thyroid peroxidase from human
      Graves' thyroid tissue.
AB  - Milligram quantities of the human membrane autoantigen thyroid peroxidase (TPO)
      have been purified to a high degree of homogeneity by a combination of detergent
      solubilisation, monoclonal antibody affinity, and ion exchange chromatography,
      from pooled Graves' disease thyroid glands. The purified TPO of greater than 90%
      purity was enzymatically active as judged by its ability to oxidise guaiacol.
      Crystals of TPO have been grown from solutions of the protein solubilised in
      sodium deoxycholate, in the presence of ammonium sulphate. The crystals exhibited
      birefringence under polarised light, indicative of molecular order.
      Crystallisation of this large, membrane autoantigen represents the first step in
      delineating the complete three-dimensional structure of a human autoantigen
      involved in destructive thyroiditis.

PMID- 9177278
TI  - Green fluorescent protein variants as markers of retroviral-mediated gene
      transfer in primary hematopoietic cells and cell lines.
AB  - Retroviral vectors are widely used for the introduction of exogenous genetic
      material into hematopoietic cells. Here we report the generation of retroviral
      vectors containing the Aequorea victoria green fluorescent protein (GFP) gene and
      improved versions thereof. Murine fibroblasts transduced with the mutant GFP
      genes demonstrated a distinct green fluorescent signal in fluorescence-activated
      cell sorter (FACS) analysis. The relative intensities of peak green fluorescence
      observed with different GFP mutants were in the order EGFP>hGFP(S65T)> GFP-PTS1
      or RSGFP>wildtype GFP (wtGFP). Furthermore, GFP-PTS1 expression was observed in
      murine (3T3, Rat2, and freshly-cultured bone marrow) and human (K562) cells
      transduced with the corresponding retroviral vector. The GFP-PTS1 positive
      phenotype could be selected for by FACS and appeared to be stable for at least 1
      month in murine fibroblasts and human K562 cells. Therefore, these GFP variants
      are convenient selectable markers to monitor retroviral-mediated gene transfer
      and expression in mammalian hematopoietic cells.

PMID- 9177279
TI  - Identification of PU.1 and Sp1 as essential transcriptional factors for the
      promoter activity of mouse tec gene.
AB  - Tec is a cytoplasmic protein-tyrosine kinase abundantly expressed in
      hematopoietic precursor cells. To investigate the mechanism regulating the
      expression of Tec molecule, we cloned and analysed 5' flanking region of mouse
      tec gene up to -2kb from the transcriptional initiation site. Luciferase assays
      using successive deletion mutants demonstrated that regions from -364 to -323 and
      from -122 to -63, which contain the consensus binding sequences for PU.1 (GGAA)
      and Sp1 (GGGCGG), respectively, are important for the transcriptional activity.
      Gel-shift and supershift assays revealed that PU.1 and Sp1 bind to the these
      regions through their consensus binding motifs. In addition, introduction of
      mutations into these motifs resulted in marked decrease in the promoter activity.
      These results indicate that PU.1 and Sp1 are essential for the transcriptional
      activity of the tec promoter and suggest that the cooperation of PU.1 and Sp1
      plays a substantial role in the preferential expression of the Tec molecule in
      the hematopoietic lineages.

PMID- 9177280
TI  - CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene
      encoding steroid 18-hydroxylase (P450C18).
AB  - Corticosterone methyloxidase I (CMO I) deficiency is an autosomal recessive
      disorder of aldosterone biosynthesis. To determine further the molecular genetic
      basis of CMO I deficiency, a patient of Turkish origin that suffered from CMO I
      deficiency was studied. Nucleotide sequencing of the PCR-amplified exons from the
      genomic DNA of this patient revealed a single point mutation CTG (leucine) CCG
      (proline) at codon 461 in exon 8 of CYP11B2, which is involved in the putative
      heme binding site of steroid 18-hydroxylase (P450(C18)). The expression study
      using a cDNA introducing the point mutation revealed that the amino acid
      substitution totally abolishes the P450(C18)p3 enzyme activities required for
      conversion of 11-deoxycorticosterone to aldosterone, even though the mutant
      product was detected in the mitochondrial fraction of the transfected cells.
      These results suggest that this point mutation causes CMO I deficiency.

PMID- 9177281
TI  - Effects of exogenous p16INK4a on growth of cells with various status of cell
      cycle regulators.
AB  - p16INK4a, a protein that inhibits cyclin-dependent kinase 4 (Cdk4) and Cdk6, is
      deficient in many human cancers and in established lines of tumor cells. It has
      been reported that transfection with cDNA for p16INK4a inhibits the growth of
      cell lines that express retinoblastoma protein (pRB). However, it is unclear
      whether the introduction of cDNA for p16INK4a affects the growth of cells that
      express p16INK4a protein. Moreover, the effects of other cell-cycle regulators on
      the inhibition of cell growth by p16INK4a remain unknown. In this study, cDNA for
      p16INK4a was used to transfect human cell lines that had various status of
      expression of RB pathway-related proteins, such as members of the RB family
      proteins and Cdk-inhibitory proteins. We found that status of p107, p130,
      p15INK4b, p18INK4c, p21Cip1, p27Kip1, cyclin D1, and Cdk4 were not correlated
      with the growth-inhibitory activity of exogenous p16INK4a. By contrast,
      transfection with cDNA for p16INK4a had a significant effect on the growth of
      cells depended on the status not only of pRB but also of p16INK4a. Although
      exogenous p16INK4a inhibited the growth of cells that expressed pRB but did not
      express p16INK4a (pRB+/p16- cells), it had little affect on either pRB+/p16+
      cells or pRB-/p16+ cells. Moreover, transfection with cDNA for p16INK4a also
      inhibited the activity of the E2 promoter of the dehydrofolate reductase gene in
      the same manner that depended on the absence of p16INK4a, as well as on the
      presence of pRB. These results suggest that deregulation of the RB pathway by
      p16INK4a deficiency plays a very important role in the proliferation of cells
      that lack p16INK4a protein.

PMID- 9177282
TI  - Complete coding sequence of hepatitis C virus genotype 6a.
AB  - Hepatitis C virus (HCV) genotype 6a is found in a restricted part of South East
      Asia, including Hong Kong, Macau and Vietnam. We determined the full length
      coding sequence of a type 6a isolate (EUHK2) obtained from a Hong Kong blood
      donor. The sequence of EUHK2 contained a single open reading frame coding for a
      polyprotein of 3018 amino acids, within the range of 3008 to 3037 for other HCV
      genotypes. The full length sequence of EUHK2 showed 30.3%-32.9% nucleotide (24.3%
      29.4% amino acid) sequence divergence from genotypes 1-4, but only 27.7% (20.7%
      amino acid) divergence from JK046 ("type 11a"). These similarity values were
      intermediate between those of other HCV genotypes (minimum 28.4%) and between
      subtypes (maximum 25%). The close evolutionary relationship of EUHK2 with JK046
      was further indicated by their grouping together by phylogenetic analysis.

PMID- 9177283
TI  - Malignant transformation of mammalian cells initiated by constitutive expression
      of the polo-like kinase.
AB  - Polo-like kinase (Plk) is the mammalian homologue of the Drosophila polo and
      Saccharomyces cerevisiae CDC5 genes, which are thought to be involved in
      regulating chromosomal segregation. Previously, we showed that transient ectopic
      expression of Plk could induce DNA synthesis in quiescent NIH 3T3 cells,
      suggesting that Plk might also have a function during G1 or S phase. Here we
      report that microinjection of Plk mRNA is sufficient to drive quiescent cells
      into mitosis and that constitutive expression of Plk in NIH 3T3 cells causes
      oncogenic focus formation. These transformed cells grow in soft agar and form
      tumors in nude mice. Because Plk expression has been shown to be high in various
      human tumors, we suggest that Plk may contribute to the promotion and/or
      progression of human cancers.

PMID- 9177285
TI  - Translocation of protein kinase C isoforms in rat neutrophils.
AB  - In this study, we examined the protein kinase C (PKC) isoforms present in cytosol
      and membrane fractions of rat neutrophils by Western blotting analysis with
      monoclonal antibodies against PKC isoforms and demonstrated that rat neutrophils
      express at least three conventional PKCs (cPKC), alpha, beta and gamma, four
      novel PKCs (nPKC), delta, epsilon, theta and mu, and three atypical PKCs (aPKC),
      iota, lambda and zeta, although PKC lambda and zeta were barely detected. Cells
      stimulated with phorbol 12-myristate 13-acetate (PMA) induce a sustained and
      marked translocation of cPKC and nPKC from the cytosol to particulate fraction. A
      concentration-dependence of PMA on the membrane translocation of PKC isoforms was
      observed. Treatment with formyl-Met-Leu-Phe (fMLP), in contrast with PMA, caused
      a transient and less prominent association of cPKC and nPKC with particulate
      fraction. However, the distribution of PKC iota isoform was affected neither by
      fMLP nor by PMA. These data indicate that the rat neutrophils contain PKCs of
      three isoform families and the membrane translocation of cPKC and nPKC was
      observed in cells in response to PMA as well as to fMLP.

PMID- 9177284
TI  - Two forms of avian(chicken) TATA-binding protein mRNA generated by alternative
      polyadenylation.
AB  - We have isolated and sequenced the cDNA encoding avian(chicken) TATA-binding
      protein (cTBP). The cTBP protein shows a significant homology to those of the
      other species, and especially its C-terminal region (180 amino acid residues) is
      identical to those of the vertebrates. By Northern blot analysis, we found that
      two transcripts with about 2.1 kb (cTBP0) and 2.7 kb (cTBP1) were expressed in
      various chicken tissues, though only one type of the TBP transcript was reported
      in vertebrates. A primer extension study demonstrated a single transcription
      start site. The analysis of the genomic structure of cTBP with the sequences of
      the two types of cTBP cDNAs(cTBP0 and cTBP1) revealed that the alternative
      polyadenylation generates two transcripts with different 3'untranslated regions
      (3'UTRs), indicating a putative role of the different 3'UTRs on the stability of
      cTBP mRNAs.

PMID- 9177286
TI  - Phosphorylation can modulate the association of different sets of RNA binding
      proteins with the Vg1 localization signal RNA.
AB  - As assayed by both in vivo and in vitro UV-crosslinking techniques, four RNA
      binding proteins, with apparent molecular weight of 56, 54, 42, and 40
      kilodaltons, associated specifically with the Xenopus Vg1 mRNA localization
      signal (LS) RNA. The 56 and 54 kD proteins were assigned as the masking proteins
      described previously, on the basis of their thermal stability and the effect of
      phosphorylation on RNA binding activity. The 42 and 40 kD proteins associated
      with the LS RNA at a lower extract concentration than the masking proteins did in
      vitro. Dephosphorylation will eliminate the RNA binding activities of all four
      proteins. However, either raising the extract concentration or phosphorylating
      the extract by the catalytic domain of protein kinase A had opposite effects on
      the crosslinking efficiencies of these two sets of RNA binding proteins.
      Phosphorylation might regulate this protein exchange process in vitro.

PMID- 9177287
TI  - Cyclosporin A-sensitive calcium signaling represses NFkappaB activation in human
      bronchial epithelial cells and enhances NFkappaB activation in Jurkat T-cells.
AB  - Activation of the NFkappaB transcription factor in 16HBE human bronchial
      epithelial cells was compared with activation of NFkappaB in Jurkat T-cells. An
      NFkappaB-luciferase reporter gene was activated by phorbol myristyl acetate (PMA)
      in both cell types. Ionomycin added to PMA (P/I) inhibited NFkappaB activation in
      epithelial cells and enhanced PMA activation in T-cells. Cyclosporin A (CsA)
      inhibited calcium signaling in both cell types. Nuclear NFkappaB DNA-binding
      stimulated with PMA was inhibited with ionomycin in epithelial cells and was
      enhanced with ionomycin in T-cells; CsA reversed both effects of ionomycin.
      Cytosolic IkappaB-alpha was regulated identically in both cell types. Thus,
      calcium activated opposing nuclear signaling pathways in epithelial cells and T
      cells. Calcium-mediated repression of NFkappaB in epithelial cells was
      derepressed by CsA, and this establishes a mechanism through which CsA may exert
      proinflammatory effects in nonlymphoid cells.

PMID- 9177288
TI  - Characterization of voltage-sensitive calcium channels in growth plate
      chondrocytes.
AB  - Growth plate chondrocytes (GPCs), cells integrally involved with the process of
      endochondral bone formation, facilitate Ca2+ infux to provide a source of ion for
      processes such as Ca2+ signaling and matrix vesicle loading. We hypothesize that
      this Ca2+ entry into GPCs is achieved through the action of voltage-sensitive
      Ca2+ channels. This hypothesis was tested by measuring intracellular [Ca2+]
      changes in fura 2-loaded GPCs that were depolarized by challenge with a K(+)
      containing medium. KCl doses between 55 and 95 mM evoked significant Ca2+
      responses that were blocked by addition of extracellular EGTA. The Ca2+ response
      evoked by 95 mM K+ was insensitive to 100 microM doses of nifedipine or
      nitrendipine, ruling out L-type channel involvement. This finding was
      corroborated by the observation that 10 microM BAY K 8644 did not activate a Ca2+
      response of its own. However, 10 microM Cd2+ significantly inhibited the 95 mM
      Ks(+)-evoked effects, suggesting N-type channel activity. Use of 1 microM Ni+ in
      an attempt to block possible T-type channel activity caused nonspecific cellular
      effects, precluding pharmacological assessment of a possible T-type channel
      activity. These data (i) provide the first direct evidence for voltage-sensitive
      Ca2+ channel activity in GPCs and (ii) suggest at least partial facilitation of
      that activity through N type channels.

PMID- 9177289
TI  - Subcellular localization of alpha-subunits of trimeric G-proteins in human
      platelets.
AB  - Following subcellular fractionation of platelet homogenates and Western blotting,
      two groups of alpha-subunits of trimeric G-proteins could be distinguished. Group
      1 consisted of alpha(i)-2, alpha(i)-3, alpha(z), alpha(s), and alpha(q) and was
      predominantly localized in membranes. Group 2 consisted of alpha16 and alph12 and
      was predominantly localized in the cytosol. Plasma membranes and dense tubular
      system (DTS)-membranes showed the same distribution of Group 1 alpha-subunits. An
      exception was alpha(q), which was virtually absent in the DTS as were Group 2
      subunits. In addition, this compartment showed a doublet for alpha(z). Group 1
      alpha-subunits were also found in fractions with the combined secretory granules
      and in separate dense granules. In addition, alpha16 was found in these granule
      fractions, but secretion granules were devoid of alpha12. These data reveal a
      heterogeneous distribution of alpha-subunits in platelet compartments and may
      indicate that G12 and G16 play different roles in platelets than members of the
      G(i) and G(s) classes and other members of the G(q) class.

PMID- 9177290
TI  - The hemopexin-type repeats of human vitronectin are recognized by Streptococcus
      pyogenes.
AB  - The specific binding of vitronectin to Streptococcus pyogenes is believed to play
      an important role in the infection process by mediating adherence of the bacteria
      to host cells. The domain of vitronectin involved in the interaction with S.
      pyogenes is unknown. In the present study, we constructed a vitronectin random
      epitope phage display library, which was used to pan against intact cells of S.
      pyogenes. Several phage-displayed vitronectin peptides containing a hydrophobic
      pentapeptide motif within the hemopexin-type repeats were found to bind to
      streptococci. These data were supported by competition experiments, in which a
      representative 23-amino acid synthetic vitronectin peptide comprising part of a
      hemopexin-type repeat inhibited binding of the bacteria to vitronectin, while a
      control peptide with identical amino acid composition but a scrambled sequence
      had no effect. Moreover, cells of S. pyogenes were shown to bind to the synthetic
      peptide as well as to immobilized hemopexin, whose structural homology to the
      hemopexin-type repeats in the vitronectin molecule has long been underlined.
      Soluble vitronectin could inhibit streptococcal binding to immobilized hemopexin.
      These results provide first evidence for a biological role of hemopexin itself
      and respective repeats in vitronectin in bacterial binding, suggesting that
      during an infection process these or other hemopexin-type repeat-containing
      proteins could be potential targets for bacterial attachment and subsequent
      colonization.

PMID- 9177291
TI  - Isolation and sequencing of two alpha-globin genes alpha(A) and alpha(D) in
      pigeon and evidence for embryo-specific expression of the alpha(D)-globin gene.
AB  - By screening a pigeon genomic DNA library, we isolated a recombinant phage clone
      containing the alpha(A)-globin gene. The DNA sequence of the approximately 6kbp
      long insert fragment of the phage clone was determined. The sequence suggested
      the existence of pigeon alpha(D)-globin gene located 3.1 kbp upstream from the
      alpha(A)-globin gene. The expression of the alpha(D)-globin in late embryo was
      also shown by the N-terminal amino-acid sequence of the intact globin chain.
      These results show that two adult alpha-globin genes, alpha(A) and alpha(D),
      exist in the pigeon genome, and the alpha(D)-globin is expressed at the late
      embryo stage. The stage-specific expression suggests the existence of regulatory
      elements and factors interacting to inhibit transcription at the adult stage.

PMID- 9177292
TI  - Interleukin-18 activates NF-kappaB in murine T helper type 1 cells.
AB  - Interleukin-18 (IL-18) activated T helper type 1 (Th1) cells, OVA#4, and induced
      production of interleukin-2 (IL-2) in costimulation with anti-CD3 antibody. Upon
      stimulation with IL-18, IkappaB disappeared from cytoplasm and subsequently
      nuclear factor-kappaB (NF-kappaB) (p65) accumulated in the nucleus. Corresponding
      with that, DNA binding activity of NF-kappaB (p65 homodimer or p65/p50
      heterodimer) was detected in the nucleus. In the transfection experiments, an IL
      2 promoter-driven reporter construct showed the similar responsiveness against IL
      18 to that of the intrinsic IL-2 gene, and a construct lacking kappaB site failed
      to respond to IL-18. These results suggest that IL-18 activates NF-kappaB and it
      is important for enhancement of IL-2 gene expression by Th1 cells stimulated with
      IL-18.

PMID- 9177294
TI  - The variable domain glycosylation in a monoclonal antibody specific to GnRH
      modulates antigen binding.
AB  - Functionally important glycosylation has been identified in the antigen binding
      domain of an anti-GnRH monoclonal antibody. Presence of mannose and sialic acid
      residues is revealed from con A immunoblots and positive staining with a sialic
      acid detection kit, respectively. Desialylation of the antibody reduces GnRH
      binding, suggesting the role of terminal sialic acid residues in modulating
      antigen binding. The crystal structure of the Fab fragment shows electron density
      adjacent to the antigen binding site which may be attributed to the covalently
      attached carbohydrate moiety. Thus, the presence of sialic acid containing
      mannose-rich carbohydrate moiety near the antigen binding site of a monoclonal
      antibody Fab fragment is relevant for defining antibody specificity.

PMID- 9177293
TI  - Models which explain the inhibition of reverse transcriptase by HIV-1-specific
      (thio)carboxanilide derivatives.
AB  - The (thio)carboxanilide derivatives are potent and selective inhibitors of HIV-1
      reverse transcriptase (RT) and have a favourable antiviral activity spectrum. To
      understand better their mode of action, and to provide a structural basis for
      further improvement, models of RT complexed with four (thio)carboxanilide
      inhibitors (UC781, UC10, UC38 and UC84) have been constructed based on the X-ray
      structure of RT complexed with 9-chloro-TIBO. In the models, the protein
      conformation is similar to that of the RT-TIBO complex and the complexes are
      stabilised by hydrogen bonding between the inhibitors and the main chain oxygen
      of Lys101. Significant hydrophobic interactions include those with Leu100,
      Val106, Val179, Tyr188, Phe227, Leu234, and His235. The thiocarboxanilides UC781
      and UC10 also make important hydrophobic interactions with Trp229. The models are
      consistent with the inhibitors' relative antiviral potencies and the observed
      resistance data. They further predict that mutations to Phe227, Trp229, or Leu234
      might confer resistance. Since these are not observed, some constraining
      structural or functional role for these residues in the active enzyme is
      suggested.

PMID- 9177295
TI  - Glutathione depletion-induced thymidylate insufficiency for DNA repair synthesis.
AB  - Dietary methionine (Met) deficiency is known to divert folate away from de novo
      biosyntheses of purines and the pyrimidine, thymidylate, to the resynthesis of
      Met resulting in deoxynucleoside triphosphate imbalance. We have recently shown
      that Met can easily be depleted and methylation can be impaired by exposure to a
      model glutathione (GSH)-depleting agent, bromobenzene (BB). GSH depletion-induced
      Met depletion, therefore, could cause thymidylate insufficiency for DNA repair
      synthesis. The administration of thymidine (Thy) should repair this impairment.
      When this hypothesis was examined in the present study, several interesting
      results were found. The administration of Thy labeled with [2-14C]Thy to BB
      treated Syrian hamsters at either 1, 5, 7 or 9 h after BB resulted in an
      attenuation of liver toxicity. Intrahepatic hemorrhage, which is a typical
      characteristic of BB toxicity in the Syrian hamster, was decreased in the BB +
      Thy groups. The attenuation of liver toxicity was accompanied by a progressive
      increase of Thy incorporation into liver genomic DNA at 24 h after BB. With
      respect to the time points chosen for Thy administration, Thy incorporation found
      in the BB + Thy groups were 2-, 2-, 3- and 4-fold of the controls that received
      only Thy. The results provide evidence that BB causes a progressive increase of
      thymidylate insufficiency in liver cells. Thymidylate insufficiency is due to Met
      depletion, a depletion that occurs as a result of GSH depletion.

PMID- 9177296
TI  - Calcium-dependent inactivation of neuronal nitric oxide synthase: evidence for
      the existence of stabilization / activation factor.
AB  - Neuronal nitric oxide synthase (nNOS; EC 1.14.13.39) activity in supernatant of
      rat cerebellum homogenate was unstable and chelating reagent protected the
      activity from the rapid decrease. The main target ion of the chelating reagent
      was found to be Ca2+. Although the enzyme was very unstable after purification by
      the procedures including DEAE-cellulose chromatography and ammonium sulfate
      precipitation, the inactivation was neither accelerated by addition of Ca2+ nor
      protected by EGTA. Upon addition of boiled supernatant of rat cerebellum
      homogenate, this purified enzyme became more active and stable, but rapid
      inactivation occurred again by addition of Ca2+, suggesting the existence of
      previously unreported Ca2(+)-dependent stabilizer / activator in the boiled
      supernatant. This factor was concentrated by organic solvent and the effects on
      the enzyme were completely canceled by addition of Ca2+ or phospholipase C
      treatment.

PMID- 9177297
TI  - Stable transfection of LLC-PK1 cells with human microsomal glutathione S
      transferase gene increases haloalkene glutathione S-conjugate formation and
      cytotoxicity.
AB  - Nephrotoxic haloalkenes undergo glutathione- and cysteine conjugate beta-lyase
      dependent bioactivation, and glutathione S-conjugate formation with haloalkenes
      as substrates is preferentially catalyzed by the hepatic microsomal glutathione S
      transferase (mGST). Porcine kidney-derived LLC-PK1 cells, which are competent to
      bioactivate glutathione and cysteine S-conjugates of haloalkenes, show low mGST
      activity. Stable transfection of LLC-PK1 cells with the gene encoding mGST would
      be expected to increase glutathione S-conjugate formation and, therefore, to
      increase haloalkene cytotoxicity. Transfection of LLC-PK1 cells with human mGST
      genes resulted in increased expression of mGST protein in microsomal fractions,
      in increased glutathione S-conjugate formation with hexachloro-1,3-butadiene and
      1-chloro-2,4-dinitrobenzene as the substrates, and in increased cytotoxicity of
      hexachloro-1,3-butadiene. In addition, transfection with mGST gene also increased
      the activity of cytosolic glutathione S-transferases.

PMID- 9177298
TI  - A thermostable D-hydantoinase isolated from a mesophilic Bacillus sp.AR9.
AB  - A thermostable hydantoinase has been characterized from a mesophilic Bacillus
      sp.AR9. The hydantoinase produced by this Bacillus sp.AR9 is strictly D-specific
      and is constitutively produced with high yields (4500 U/ml) in this strain. The
      enzyme is not only alkalo- and thermostable but has a pH and temperature optimum
      of 9.5 and 65 degrees C, respectively, which is advantageous for the
      bioconversion of DL-5-monosubstituted-hydantoin derivatives. The enzyme has a
      half life of 80 minutes at 70 degrees C and loses only 33% of its activity in 4
      hr at 60 degrees C. The enzyme has a broad substrate specificity with a maximum
      of 100% with hydantoin and about 26% with dihydrouracil. Co+ + ions enhance the
      activity of the enzyme by more than 60%.

PMID- 9177299
TI  - Expression of the JNK2-alpha1 gene in the developing chick brain.
AB  - We have isolated chicken JNK2-alpha1 encoding a c-Jun N-terminal kinase, and
      examined the expression during embryogenesis. The kinase domain sequence is well
      conserved between chicken and mammals, but carboxy-terminal sequence of JNK is
      divergent from subtype 1 and 2, possibly derived from alternative splicing. The
      JNK2-alpha1 gene is preferentially expressed in the neuroepithelium of developing
      brain at stages 16-26, and transcripts are not detectable in the other region
      including spinal cord. These results suggest that JNK2-alpha1 is involved in
      development of the central nervous system as a mediator of stress-activated
      protein kinase pathway conferring competence to the external stimuli such as
      growth factors.

PMID- 9177300
TI  - Expression of vascular endothelial growth factor at the human gastric ulcer
      margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric
      ulcer healing.
AB  - Angiogenesis plays a pivotal role in gastric ulcer repair. Several growth factors
      are involved in angiogenesis, and of these, vascular endothelial growth factor
      (VEGF) has received considerable attention, since it is the only factor that
      specifically acts on endothelial cells. However, the role of VEGF in gastric
      ulcer repair is not known. In the present study, we demonstrate the specific
      expression of VEGF at the gastric ulcer margin, using immunohistochemistry and RT
      PCR. The specific receptors of VEGF, flt-1 and KDR were also detected in gastric
      mucosa. We further demonstrate the expression of VEGF by cultured human gastric
      fibroblasts which is enhanced by tumor necrosis factor-alpha. These data suggest
      that VEGF may play a role in angiogenesis in the process of gastric ulcer
      healing.

PMID- 9177301
TI  - Cloning, characterization, and cellular distribution of rat scavenger receptor
      class B type I (SRBI) in the ovary.
AB  - An immediately inducible gene by gonadotropin was isolated from rat ovaries
      primed with pregnant mare serum gonadotropin (PMSG) by using a subtraction
      cloning procedure. Homology analysis revealed that the gene is a rat homologue of
      scavenger receptor class B-I, which was recently identified as a specific
      receptor for high density lipoprotein (HDL). The structure of rat SRBI was
      determined by nucleotide sequence analysis of full-length cDNAs for SRBI.
      Northern blot analysis revealed that rat SRBI mRNA levels were rapidly and
      strongly increased within 3 h by the injection of PMSG. In situ hybridization
      study revealed that SRBI mRNA was strongly induced in theca interna cells of
      immature rat ovary stimulated with 30 IU of PMSG for 6 h. SRBI mRNA expression
      was also observed in corpora lutea of the adult rat ovary. These findings
      indicate that expression of SRBI mRNA is restricted to and induced in the ovarian
      steroidogenic cell types where cholesterol is used as a substrate for synthesis
      of steroid hormones. Our data strongly suggest that SRBI may play a significant
      role in the ovarian steroidogenesis by mediating selective uptake of cholesterol
      from HDL to ovarian theca interna cells or to corpus luteum.

PMID- 9177302
TI  - A novel inhibitor of bacterial endotoxin derived from cinnamon bark.
AB  - A substance that inhibits the activity of bacterial endotoxin (LPS) was found in
      cinnamon bark. The inhibitor, extracted from dry cinnamon bark with 67%
      ethanol/water, was purified by using Limulus gelation activity as an indicator of
      endotoxin activity. The inhibitor suppressed the activity of the LPS when it was
      mixed with the inhibitor prior to the assay. The reduction of the LPS activity
      depended on the concentration of both the inhibitor and LPS when mixed, and also
      on the incubation time. The inhibitor suppressed the activity of all LPS and
      lipid A preparations tested regardless of the origin of the bacteria. The
      inhibitor alone did not affect the Limulus system. These results indicate that
      the inhibition was caused by direct interaction of the inhibitor with the LPS
      molecule. Furthermore the inhibitor abrogated the pyrogenicity of the LPS.
      Although it is uncertain whether the inhibitor actually plays a role in the
      defense mechanism in cinnamon bark, this is the first report that an inhibitor of
      bacterial endotoxin exists in a plant.

PMID- 9177303
TI  - Mutation analysis of the ND6 gene in patients with Lebers hereditary optic
      neuropathy.
AB  - DNA sequence analysis of the gene encoding subunit 6 of the NADH-ubiquinone
      oxidoreductase complex (ND6) in human mitochondria was performed in 25
      independent patients who suffer from Lebers hereditary optic neuropathy (LHON).
      In 10 cases the well-known LHON mutation at nucleotide position (np) 14484 was
      detected. Furthermore, silent substitutions at np14167 and np14527 and missense
      mutations at np14498, np14564, np14568, and np14582 were found in individual
      patients. The np14498 and np14568 mutations were found in patients who present a
      typical clinical picture and course of LHON but lack any of the canonical mtDNA
      mutations. The np14568 mutation, which replaces a moderately conserved glycine by
      a serine residue, was observed in a single male patient and subsequently excluded
      in 175 independent controls. The mutation at np14498, which replaces an
      evolutionarily highly conserved tyrosine with a cysteine, was found in a
      multigeneration family with four affected members, the eldest carrying a
      heteroplasmic mixture of mutated and wildtype mtDNA molecules. None of 170
      analyzed control subjects carried this mutation. These findings provide evidence
      that several allelic ND6 gene mutations may be involved in Lebers hereditary
      optic neuropathy.

PMID- 9177304
TI  - Amplified restriction fragment length polymorphism-based mRNA fingerprinting
      using a single restriction enzyme that recognizes a 4-bp sequence.
AB  - Using amplified restriction fragment length polymorphism (AFLP) technology, we
      have developed a new protocol for the fingerprinting of mRNA that allows
      systematic comparison of the differential expression of genes between mRNA
      samples. The major advantage of our protocol is the use of only a single
      restriction enzyme that recognizes a 4-bp sequence but allows screening of large
      numbers of different cDNAs. Using this new protocol, we compared mRNA samples
      obtained from the flower buds of two lines of the common morning glory (Ipomoea
      purpurea) with red and white flowers, respectively. Approximately 50 bands were
      observed in each lane of a denaturing polyacrylamide gel and the results were
      highly reproducible, as indicated by the results of analysis of two sets of
      independent mRNA samples. Two cDNA fragments, which were differentially amplified
      in the samples from the two lines, were shown to have been derived from a single
      gene that was actively expressed in the buds of red flowers but not in those of
      white flowers. A full-length cDNA of this gene was cloned from a bud cDNA
      library. Sequence analysis showed that this cDNA carries a sequence highly
      homologous to the chalcone synthase (CHS) genes, the key enzyme in the flavonoid
      biosynthetic pathway.

PMID- 9177305
TI  - Identification of cellular recognition sequence of epimorphin and critical role
      of cell/epimorphin interaction in lung branching morphogenesis.
AB  - A mesenchymal protein, epimorphin, is known to bind directly to the cell surface
      through its central portion and to act as a signaling molecule for epithelial
      morphogenesis. Utilizing several recombinant polypeptides and synthetic peptides,
      we identified the cellular recognition sequence of epimorphin in the central
      portion of this molecule (amino acids 105-123, NGNRTSVDLRIRRTQHSVL; termed NL
      peptide sequence). Interestingly, although a model cell type bound to the NL
      peptide as strong as to the full-length epimorphin, this peptide itself didn't
      induce the cellular functional responses so far tested. We found that the NL
      peptide behaved as an antagonist for the endogenous epimorphin and severely
      perturbed lung branching morphogenesis in organ culture. These results not only
      revealed a part of the functional mechanism of epimorphin but also demonstrated
      that cell/ epimorphin interaction through the NL-peptide sequence is a critical
      step for lung epithelial morphogenesis.

PMID- 9177306
TI  - Bromodeoxyuridine-induced expression of endothelin A in A375 human melanoma
      cells.
AB  - Expression of endothelin (ET) receptor subtypes was examined in an experimental
      model of A375 human melanoma cell differentiation using the pyrimidine analog
      bromodeoxyuridine (BUdR). BUdR (10 microM)-treated cells had an increased surface
      area and an increased dendricity, were contact-inhibited and lacked
      tumorigenecity in athymic nude mice. The untreated A375 cells exclusively
      expressed ETB and BUdR-induced phenotypical changes were accompanied by induction
      of ETA expression as evidenced by northern blotting, [125I]ET-1 binding assay and
      [Ca2+]i measurement. Thus, BUdR-induced differentiation of A375 melanoma cells
      may provide a model system to study the receptor subtype switch in melanocyte
      development.

PMID- 9177307
TI  - Synthetic peptides corresponding to various hydrophilic regions of the large
      subunit of cytochrome b558 inhibit superoxide generation in a cell-free system
      from neutrophils.
AB  - Cytochrome b558 is a component of the superoxide-generating system in neutrophils
      and plays key roles in both the assembly of a functional complex with cytosolic
      proteins and shuttling an electron from NADPH to molecular oxygen. To determine
      the role of predicted hydrophilic domains of gp91-phox, a glycosylated subunit of
      the cytochrome, we synthesized peptides corresponding to the regions and tested
      whether they affected superoxide generation in the cell-free system obtained from
      human neutrophils. Among twelve peptides tested, six peptides, four of which
      correspond to previously unreported regions, inhibited superoxide generation in
      the cell-free system. All of the active peptides were effective when added to the
      system before activation with sodium dodecyl sulfate. Four peptides, including
      two peptides corresponding to two newly identified regions, inhibited the
      translocation of the cytosolic components, p47-phox and p67-phox. The extent of
      inhibition on translocation of these components varied depending on the peptide
      used.

PMID- 9177308
TI  - Expression of the psbA gene during photoinhibition and recovery in Synechocystis
      PCC 6714: inhibition and damage of transcriptional and translational machinery
      prevent the restoration of photosystem II activity.
AB  - The D1 reaction center protein of the photosystem II complex is very sensitive to
      light. It is continuously being damaged, degraded and resynthesized. Under high
      light, photosystem II inactivation is observed. This is because the rate of D1
      damage is faster than that of its replacement. This process can be reversed if
      exposure to high light is not too long. In this work we study the changes that
      occur in the transcriptional and translational machinery that could lead to
      irreversible photoinhibition in Synechocystis PCC 6714. In the first minutes of
      photoinhibition, high light induced an accumulation of psbA mRNA due to an
      increase in psbA transcription initiation. Although the transcription rate of
      other photosynthetic genes (e.g. psaE and cpcB-cpcA) declined, the high turnover
      of the psbA transcript was maintained for a long time. When the light stress was
      too long, the stability of psbA mRNA increased and the psbA transcription rate
      appeared to decrease. A high level of psbA mRNA was maintained even though
      translation no longer occurred and the cells were unable to recover. Experiments
      to measure newly synthesized D1 incorporation into the thylakoid membranes during
      recovery in the presence of rifampicin showed that the initiation of
      transcription was not required for translation of psbA mRNA when photoinhibition
      was still reversible. Since psbA translation did not depend on the level of psbA
      transcript or on the initiation of psbA transcription, we propose that damage to
      the translational machinery also occurred during light stress, leading to the
      inhibition of D1 synthesis and to irreversible photoinhibition.

PMID- 9177309
TI  - Expression of de novo high-lysine alpha-helical coiled-coil proteins may
      significantly increase the accumulated levels of lysine in mature seeds of
      transgenic tobacco plants.
AB  - We have designed protein molecules based on an alpha-helical coiled-coil
      structure. These proteins can be tailored to complement nutritionally unbalanced
      seed meals. In particular, these proteins may contain up to 43% mol/mol of the
      essential amino acid lysine. Genes encoding such proteins were constructed using
      synthetic oligonucleotides and the protein stability was tested for in vivo by
      expression in an Escherichia coli model system. A protein containing 31% lysine
      and 20% methionine (CP 3-5) was expressed in transgenic tobacco seeds utilizing
      the seed specific bean phaseolin and soybean beta-conglycinin promoters. Both
      promoters provided a level of expression in the mature transgenic tobacco seeds
      which resulted in a significant increase in the total lysine content of the
      seeds. Several of these transgenic lines were analyzed for three generations to
      determine the stability of gene expression. Plants transformed with the soybean
      beta-conglycinin promoter/CP 3-5 gene consistently expressed the high-lysine
      phenotype through three generations. However, expression of the high-lysine
      phenotype in plants transformed with the bean phaseolin/CP 3-5 was variable. This
      is the first report of a significant increase in seed lysine content due to the
      seed-specific expression of a de novo protein sequence.

PMID- 9177310
TI  - Potato SNF1-related protein kinase: molecular cloning, expression analysis and
      peptide kinase activity measurements.
AB  - A polymerase chain reaction product (PKIN503) was amplified from potato (Solanum
      tuberosum) cv. Desiree using oligonucleotide primers with sequences which are
      highly conserved in the plant sucrose non-fermenting 1 (SNF1)-related protein
      kinase gene family. Southern blot analysis showed the presence of 5-10 SNF1
      related genes in the potato genome. PKIN503 was used to screen a tuber cDNA
      library and a genomic library, and one cDNA and five genomic clones were
      isolated. The nucleotide sequences of a portion of all five genomic clones were
      shown to be identical and only one, pgPKIN1, was analysed further. The cDNA was
      found to be truncated at the 5' end but the cDNA and genomic sequences contained
      only 15 substitutions, two of which resulted in changes in the derived amino acid
      sequence. PKIN1 was shown to encode an Mr 57,854 protein with 61-70% sequence
      similarity with other plant SNF1-related protein kinases. Northern blot analysis
      revealed some tissue-specific differences in PKIN1 transcript levels, the lowest
      being detected in leaves and the highest in stolons. However, much greater
      differences were found in SNF1-related activity, which was measured using a
      phosphorylation assay with a substrate peptide which has been shown previously to
      be phosphorylated by plant SNF1-related protein kinases. Activity decreased by
      almost 80% during development from stolons to mature tubers but it increased
      about seven-fold during the first seven days of storage after harvesting, before
      decreasing again. However, activity was highest in mini-tubers, where the levels
      were 37 times greater than those in mature tubers from a pot-grown plant.
      Transcript levels in these tissues were approximately equal, clear evidence that
      SNF1-related protein kinase activity in potato is regulated, in part, post
      transcriptionally.

PMID- 9177311
TI  - Expression of ethylene biosynthetic genes in Actinidia chinensis fruit.
AB  - The fruit of Actinidia chinensis, a diploid relative of kiwifruit, showed an
      increased rate of ripening in response to the application of exogenous ethylene.
      Moreover, late in ripening the fruit produced a burst of ethylene biosynthesis.
      Thus ripening is climacteric, and there is a clear temporal separation of
      ethylene sensitivity and ethylene production. RNase protection assays were used
      to monitor transcript levels of ethylene biosynthetic genes during fruit
      development and ethylene-induced ripening. The application of exogenous ethylene
      correlated with increased transcript levels for three different S-adenosyl-L
      methionine (SAM) synthetase genes and for the 1-aminocyclopropane-1-carboxylate
      (ACC) oxidase gene family. Transcription of an ACC synthase gene was not affected
      by exogenous ethylene. However, ACC synthase transcript levels increased during
      subsequent ethylene production by the fruit, consistent with this being the
      control step for the onset of climacteric ethylene production. ACC oxidase
      transcripts increased significantly both prior to and during climacteric ethylene
      production, while only one of the three SAM synthetase transcripts was induced
      during the late ethylene burst. We propose that the regulation of SAM synthetase
      transcripts by ethylene may occur as part of the methionine salvage pathway.

PMID- 9177312
TI  - A phosphate-starvation inducible beta-glucosidase gene (psr3.2) isolated from
      Arabidopsis thaliana is a member of a distinct subfamily of the BGA family.
AB  - We have previously isolated a phosphate starvation-response (psr) cDNA clone,
      psr3.1, from Brassica nigra which encodes a beta-glucosidase. Southern blots of
      Arabidopsis thaliana genomic DNA probed with the psr3.1 cDNA indicated that this
      gene exists as a single locus. A genomic library of A. thaliana was screened at
      high stringency to isolate the corresponding genomic clone. The resultant clone
      was coined psr3.2 because of its sequence divergence from isolated psr3.1 cDNA
      clones. Northern blotting with probes derived from the coding region of the
      genomic clone showed that this gene is expressed at high levels in P(i)-starved
      roots and the enhancement occurred within two days of growth in medium lacking
      P(i). The expression of this gene is repressed by heat shock and anaerobic
      conditions, and it is not significantly induced by high salinity, or by nitrogen
      or sulfur deprivation. Sequence analysis of the genomic clone revealed the
      existence of 13 exons interrupted by 12 AT-rich introns and it possessed a high
      homology with the B. nigra psr3.1 as well as various other beta-glucosidase genes
      from other species. Sequence similarity and divergence percentages between the
      deduced amino acid sequences of the psr3 clones and other beta-glycosidases
      suggests that they should be included along with two other Brassicaceae genes in
      a distinct subfamily of the BGA glycosidase gene family. The presence of an
      endoplasmic reticulum retention signal at the carboxy terminus indicates the
      likely cellular location of PSR3.2. The possible metabolic and regulatory roles
      of this enzyme during the P(i)-starvation response are discussed.

PMID- 9177314
TI  - Interaction of tobacco nuclear protein with an elicitor-responsive element in the
      promoter of a basic class I chitinase gene.
AB  - The expression of tobacco class I chitinase genes is effectively induced by a
      fungal elicitor in suspension-cultured cells. A putative cis-acting elicitor
      responsive element (EIRE) was identified previously in the promoter of the class
      I chitinase gene, CHN5O. To confirm that the EIRE sequence directly mediates the
      regulation of gene expression by the elicitor, I constructed a deleted promoter
      that controlled a reporter gene for beta-glucuronidase (gus) and examined
      expression of the construct in transgenic tobacco calli. Both expression and
      responsiveness to the elicitor disappeared, when the region of the promoter that
      included the EIRE sequence had been deleted. To define the specific sequence
      within the EIRE that interacts with nuclear factor(s), a gel mobility shift assay
      was performed with wild-type and mutated elements. Results of binding and
      competition experiments revealed that the nuclear factor(s) bound specifically to
      the sequence motif, (-534)GGTCANNNAGTC(-523), and that both of the repeated sites
      were involved in the binding of the nuclear factors. Moreover, the binding was
      influenced by the distance between the two repeated sites. In addition, the
      elicitor-inducible activity of the binding to this motif was reduced in nuclear
      extracts prepared from the cells that had been treated with cycloheximide or
      staurosporine.

PMID- 9177313
TI  - Restoration of TATA-dependent transcription in a heat-inactivated extract of
      tobacco nuclei by recombinant TATA-binding protein (TBP) from tobacco.
AB  - We isolated a complementary DNA (cDNA) that encoded a TATA-binding protein (TBP)
      from a cDNA library of tobacco (Nicotiana tabacum) suspension-cultured cells (BY
      2). A comparison among deduced amino acid sequences of plant TBPs revealed the
      presence of a long conserved region within the amino acid sequence of the TBP.
      Genomic Southern analysis revealed that tobacco TBP (tTBP) is encoded by only a
      small number of copies of a gene in the tobacco genome. Addition of recombinant
      tTBP to an extract of tobacco nuclei (TNE) enhanced the basal transcriptional
      activity in vitro. This result indicates that the level of tTBP is a rate
      limiting factor for basal transcriptional activity in TNE. We subsequently
      succeeded in the functional complementation of TATA-dependent initiation of
      transcription that was associated with a plant promoter in a homologous plant
      system. Addition of bacterially expressed recombinant tTBP to a heat-inactivated
      TNE restored transcriptional activity, as did the addition of human TBP.
      Moreover, heating of the recombinant tTBP eliminated its ability to restore
      transcriptional activity. It appears that the heat inactivation of TNE was caused
      by the heat inactivation of tTBP in TNE.

PMID- 9177315
TI  - Ethylene biosynthetic genes are differentially expressed during carnation
      (Dianthus caryophyllus L.) flower senescence.
AB  - Ethylene production and expression patterns of an 1-aminocyclopropane-1
      carboxylic acid (ACC) oxidase (CARAO1) and of two ACC synthase (EC 4.4.1.14)
      genes (CARACC3 and CARAS1) were studied in floral organs of cut carnation flowers
      (Dianthus caryophyllus L.) cv. White Sim. During the vase life and after
      treatment of fresh flowers with ethylene, production of ethylene and expression
      of ethylene biosynthetic genes first started in the ovary followed by the styles
      and the petals. ACC oxidase was expressed in all the floral organs whereas,
      during the vase life, tissue-specific expression of the two ACC synthase genes
      was observed. After treatment with a high ethylene concentration, tissue
      specificity of the two ACC synthase genes was lost and only a temporal difference
      in expression remained. In styles, poor correlation between ethylene production
      and ACC synthase (CARAS1) gene expression was observed suggesting that either
      activity is regulated at the translational level or that the CARAS1 gene product
      requires an additional factor for activity. Isolated petals showed no increase in
      ethylene production and expression of ethylene biosynthetic genes when excised
      from the flower before the increase in petal ethylene production (before day 7);
      showed rapid cessation of ethylene production and gene expression when excised
      during the early phase of petal ethylene production (day 7) and showed a pattern
      of ethylene production and gene expression similar to the pattern observed in the
      attached petals when isolated at day 8. The interorgan regulation of gene
      expression and ethylene as a signal molecule in flower senescence are discussed.

PMID- 9177316
TI  - An extracellular insoluble inhibitor of cysteine proteinases in cell cultures and
      seeds of carrot.
AB  - An 18 kDa extracellular insoluble protein (EIP18) was found previously in
      amorphous particles suspended in the culture medium and in the interspaces of
      cell clusters of carrot (Daucus carota L.) callus, as well as in the
      extracellular spaces of carrot seeds, being located both in the embryo and at the
      inner edge of the endosperm. We purified EIP18 by washing the amorphous particles
      with the mixture of Triton X-100, NaCl and ethylenediaminetetraacetic acid
      (EDTA). We determined several partial amino acid sequences, and then we cloned
      and sequenced a cDNA for EIP18. EIP18 was found to consist of 133 amino acid
      residues that included a signal sequence, but it did not contain cysteine, sites
      for N-linked glycosylation or hydrophobic regions. Since its sequence was found
      to be homologous to that of inhibitors of cysteine proteinases, namely cystatins,
      EIP18 was renamed EICC (extracellular insoluble cystatin of carrot). EICC
      expressed in yeast was also found in an insoluble form in yeast cell walls. EICC
      prepared from the culture medium of carrot cells inhibited commercial cysteine
      proteinases and a proteinase extracted from germinating carrot seeds. The
      expression of the gene for EICC was detected in developing seeds, and the level
      of its transcript was markedly enhanced upon treatment of somatic embryos with
      abscisic acid.

PMID- 9177317
TI  - Identification of a delta-TIP cDNA clone and determination of related A and D
      genome subfamilies in Gossypium species.
AB  - Tonoplast intrinsic proteins (TIPs) have been implicated in the process of cell
      elongation, such as occurs in the developing cotton fiber. We have isolated a
      cDNA clone (997 bp in length) from a cotton (Gossypium hirsutum L.) library which
      putatively encodes a protein of 248 residues (Mr 25079) with 85% identity to
      Arabidopsis delta-TIP. The derived amino acid sequence included two conserved
      sequences associated with major intrinsic proteins (SGxHxNPA at residues 78 to
      85, NPA residues at 197 to 199) and a cysteine residue at 116 which is reported
      to bind mercury in Arabidopsis delta-TIP. The polymerase chain reaction was used
      to generate partial genomic clones of the cotton delta-TIP. In comparison to
      other genomic TIP sequences, the number (two) and position of the introns were
      conserved in cotton. Comparing the TIP sequences from cotton revealed two
      subfamilies, which were consistently distinguished by a Tsp45I restriction site
      polymorphism. This polymorphism was used to demonstrate that TIP subfamilies were
      specific to either the A or D genomes of Gossypium. When delta-TIP DNA fragments
      were amplified from cDNA of fiber 14 days after anthesis, the A and D were found,
      indicating the presence of delta-TIP transcripts in these elongating cells.

PMID- 9177318
TI  - A new Arabidopsis nucleic-acid-binding protein gene is highly expressed in
      dividing cells during development.
AB  - An Arabidopsis thaliana cDNA encoding a new RNA-binding protein (RBP37) was
      cloned from a silique cDNA library. The predicted amino acid sequence corresponds
      to a RBP containing two RNA recognition motifs (RRM) and a basic domain. An
      affinity for nucleic acids was confirmed in binding assays using in vitro
      synthesised AtRBP37 protein. In situ hybridisation experiments on sections of
      flowers and siliques showed expression only in growing organs: gynoecium, petals,
      filaments and during early-embryogenesis expression is located in the embryo
      proper and the suspensor up to late heart stage. Expression is not detected in
      the embryo during maturation. This results suggests an expression pattern
      correlated with dividing cells.

PMID- 9177319
TI  - Silencing of a beta-1,3-glucanase transgene is overcome during seed formation.
AB  - Expression of a beta-1,3-glucanase transgene (gn1) driven by the CaMV 35S
      promoter is silenced in the T17 homozygous tobacco transgenic line. This
      silencing process is post-transcriptionally regulated and subject to
      developmental control. We have examined this phenomenon to investigate the
      developmental pathways involved in suppression and reactivation of gn1 expression
      as well as to identify the plant tissues where these processes occur. Analysis of
      beta-1,3-glucanase activity and gene expression have allowed us to determine that
      suppression of gn1 is a very efficient process reducing the steady-state gn1 mRNA
      level, simultaneously, in all leaves of the plant. Gene silencing occurs a few
      weeks after seed germination, and is maintained throughout vegetative growth and
      floral development. Expression of gn1 is restored in the maturing fruit some time
      after fertilization. In situ hybridization analyses show that expression of gn1
      is restored within the developing seeds in tissues derived from meiotically
      divided cells. In contrast to the high level of expression found in seedlings
      obtained from germinated T17 homozygous seeds, the expression of gn1 is not
      reactivated in plantlets regenerated in vitro from leaf explants of suppressed
      T17 homozygous plants that is, in plant tissues obtained by mitotic division.
      Thus, reactivation of gn1 expression specifically occurs along the developmental
      programme controlling sexual reproduction and likely throughout epigenetic
      modifications affecting the state of gene expression during meiosis.

PMID- 9177320
TI  - Lysine-rich modified gamma-zeins accumulate in protein bodies of transiently
      transformed maize endosperms.
AB  - During maize seed development, endosperm cells synthesize large amounts of
      storage proteins, alpha-, beta-, and gamma-zeins, which accumulate within
      endoplasmic reticulum (ER)-derived protein bodies. The absence of lysine in all
      zein polypeptides results in an imbalance in the amino acid composition of maize
      seeds. We modified the maize gamma-zein gene through the introduction of lysine
      rich (Pro-Lys)n coding sequences at different sites of the gamma-zein coding
      sequence. Maize endosperms were transiently transformed by biolistic bombardment
      with Lys-rich gamma-zein constructs under the control of the 1.7 kb gamma-zein
      seed-specific promoter and the cauliflower mosaic virus (CaMV) 35S promoter. When
      (Pro-Lys)n sequences were inserted contiguous to or in substitution of the Pro
      Xaa region of the gamma-zein, high levels of protein were observed. In contrast,
      when (Pro-Lys)n sequences were inserted five residues from the C-terminal, the
      transcript was present but modified protein was not detected. These results
      suggest that only an appropriate positioning of Lys-rich inserts leads to the
      modified molecule displaying correct folding and stability. Subcellular
      localization analyses and immunoelectron microscopy studies on isolated protein
      bodies demonstrated that modified gamma-zeins accumulate within these organelles
      and co-localized with endogenous alpha- and gamma-zeins. The studies reported
      here show the feasibility of manipulating the gamma-zein gene in order to obtain
      stable and correctly targeted Lys-rich zeins in maize seeds.

PMID- 9177321
TI  - Role of PSII-L protein (psbL gene product) on the electron transfer in
      photosystem II complex. 1. Over-production of wild-type and mutant versions of
      PSII-L protein and reconstitution into the PSII core complex.
AB  - To establish a system for over-production of PSII-L protein which is a component
      of photosystem II (PSII) complex, a plasmid designated as pMAL-psbL was
      constructed and expressed in Escherichia coli JM109. A fusion protein of PSII-L
      and maltose-binding proteins (53 kDa on SDS-PAGE) was accumulated in E. coli
      cells to a level of 10% of the total protein upon isopropyl-beta-D
      thiogalactopyranoside (IPTG) induction. The carboxyl-terminal part of 5.0 kDa was
      cleaved from the fusion protein and purified by an anion exchange column
      chromatography in the presence of detergents. This 5.0 kDa protein was identified
      as PSII-L by amino-terminal amino acid sequence analysis and the chromatographic
      behavior on an anion exchange gel. A few types of mutant PSII-L were also
      prepared by the essentially same procedure except for using plasmids which
      contain given mutations in psbL gene. Plastoquinone-9 (PQ-9) depleted PSII
      reaction center core complex consisting of D1, D2, CP47, cytochrome b-559 (cyt b
      559), PSII-I and PSII-W was reconstituted with PQ-9 and digalactosyldiglyceride
      (DGDG) together with the wild-type or mutant PSII-L produced in E. coli or
      isolated PSII-L from spinach. Significant difference between the wild-type PSII-L
      proteins from E. coli and spinach was not recognized in the effectiveness to
      recover the photo-induced electron transfer activity in the resulting complexes.
      The analysis of stoichiometry of PQ-9 per reaction center in the PQ-9
      reconstituted PS II revealed that two molecules of PQ-9 were reinserted into a
      reaction center independent of the presence or absence of PSII-L. These results
      suggest that PSII-L recovers the electron transfer activity in the reconstituted
      RC by a mechanism different from the stabilization of PQ-9 in the Q(A) site of
      PSII. Ubiquinone-10 (UQ-10), but not plastoquinone-2 (PQ-2), substituted PQ-9 for
      recovering the PSII-L supported electron transfer activity in the reconstituted
      PSII reaction center complexes. The results obtained with the mutant PSII-L
      proteins revealed that the carboxyl terminal part rather than amino terminal part
      of PSII-L is crucial for recovering the electron transfer activity in the
      reconstituted complexes.

PMID- 9177322
TI  - Expression in anthers of two genes encoding Brassica oleracea transmembrane
      channel proteins.
AB  - Screening of an anther cDNA expression library resulted in the isolation of two
      almost identical cDNA clones, termed mipA and mipB, showing homology with
      sequences encoding transmembrane channel proteins from the MIP family. Both
      clones were expressed in several tissues, but not in pollen. MipA was
      preferentially expressed in the surrounding sporophytic tissues of stamens.
      Anthers subjected to drought were induced to accumulate even more mip
      transcripts, which was entirely due to higher mipA gene expression. On basis of
      isolation procedures, sequence homology and drought inducibility of mipA we
      conclude that the encoded proteins probably are constituents of the pollen coat
      and are aquaporins.

PMID- 9177323
TI  - RAP-1 is an Arabidopsis MYC-like R protein homologue, that binds to G-box
      sequence motifs.
AB  - An Arabidopsis cDNA clone encoding a DNA-binding protein, RAP-1, was isolated by
      southwestern screening of an Escherichia coli cDNA expression library. The
      protein contains a bHLH DNA-binding domain and is homologous to R proteins,
      regulating anthocyanin biosynthesis. RAP-1 binds to the sequence CACNTG. It is
      encoded by a single gene, which is expressed to high levels in root and stem and
      to low levels in leaf and flower. No expression could be detected in siliques.
      Rap-1 does not correspond to one of the known loci involved in anthocyanin
      biosynthesis, since it is located at a different map position. In contrast to the
      maize R protein Lc, RAP-1 did not induce anthocyanin biosynthesis in pea
      cotyledons. Thus, RAP-1 is a novel member of the bHLH class of DNA-binding
      proteins.

PMID- 9177324
TI  - AtPLC2, a gene encoding phosphoinositide-specific phospholipase C, is
      constitutively expressed in vegetative and floral tissues in Arabidopsis
      thaliana.
AB  - A cDNA encoding a phosphoinositide-specific phospholipase C (PI-PLC) from the
      higher plant Arabidopsis thaliana was cloned and characterized. The gene
      corresponding to this cDNA is designated AtPLC2. The overall structure of the
      predicted AtPLC2 protein is similar to those of plant PI-PLCs and mammalian delta
      type PI-PLCs. Northern blot analysis revealed that AtPLC2 is expressed
      constitutively whereas AtPLC1S, another gene for PI-PLC of Arabidopsis, is
      induced by environmental stresses such as dehydration and salinity, indicating
      that the function of AtPLC2 is distinct from that of AtPLC1S. The AtPLC2 mRNA was
      detected in vegetative and floral tissues. We determined the positions of these
      two PI-PLCs genes on Arabidopsis chromosomes by RFLP mapping using P1 genomic
      clones.

PMID- 9177325
TI  - Germany rejects genome data 'isolation'.

PMID- 9177326
TI  - European ethics advisers back cloning ban.

PMID- 9177327
TI  - EU eliminates citation gap with America.

PMID- 9177328
TI  - Italian universities move to peer review for grants.

PMID- 9177329
TI  - Geologist loses 'creationism' challenge.

PMID- 9177330
TI  - US threat to end science agreement with India over patent law.

PMID- 9177331
TI  - Patents and royalties.

PMID- 9177332
TI  - Words and rules in the human brain.

PMID- 9177333
TI  - Molecular systematics. The platypus put in its place.

PMID- 9177335
TI  - Circadian rhythms. Time to get excited by GABA.

PMID- 9177336
TI  - Biosensors. Switching channels makes sense.

PMID- 9177337
TI  - Microbial genetics. Hypermutation under stress.

PMID- 9177338
TI  - Norman Pirie (1907-97)

PMID- 9177339
TI  - Why drinking green tea could prevent cancer.

PMID- 9177340
TI  - Salt enhances flavour by suppressing bitterness.

PMID- 9177341
TI  - Structures of mollusc shell framework proteins.

PMID- 9177342
TI  - Functional rafts in cell membranes.
AB  - A new aspect of cell membrane structure is presented, based on the dynamic
      clustering of sphingolipids and cholesterol to form rafts that move within the
      fluid bilayer. It is proposed that these rafts function as platforms for the
      attachment of proteins when membranes are moved around inside the cell and during
      signal transduction.

PMID- 9177343
TI  - Chiral discrimination using piezoelectric and optical gas sensors.
AB  - Odour perception in humans can sometimes discriminate different enantiomers of a
      chiral compound, such as limonene. Chiral discrimination represents one of the
      greatest challenges in attempts to devise selective and sensitive gas sensors.
      The importance of such discrimination for pharmacology is dear, as the
      physiological effect of enantiomers of drugs and other biologically active
      molecules may differ significantly. Here we describe two different sensor systems
      that are capable of recognizing different enantiomers and of qualitatively
      monitoring the enantiomeric composition of amino-acid derivatives and lactates in
      the gas phase. One sensor detects changes in mass, owing to binding of the
      compound being analysed (the 'analyte'), by thickness shear-mode resonance; the
      other detects changes in the thickness of a surface layer by reflectometric
      interference spectroscopys. Both devices use the two enantiomers of a chiral
      polymeric receptor, and offer rapid on-line detection of chiral species with high
      selectivity.

PMID- 9177344
TI  - A biosensor that uses ion-channel switches.
AB  - Biosensors are molecular sensors that combine a biological recognition mechanism
      with a physical transduction technique. They provide a new class of inexpensive,
      portable instrument that permit sophisticated analytical measurements to be
      undertaken rapidly at decentralized locations. However, the adoption of
      biosensors for practical applications other than the measurement of blood glucose
      is currently limited by the expense, insensitivity and inflexibility of the
      available transduction methods. Here we describe the development of a biosensing
      technique in which the conductance of a population of molecular ion channels is
      switched by the recognition event. The approach mimics biological sensory
      functions and can be used with most types of receptor, including antibodies and
      nucleotides. The technique is very flexible and even in its simplest form it is
      sensitive to picomolar concentrations of proteins. The sensor is essentially an
      impedance element whose dimensions can readily be reduced to become an integral
      component of a microelectronic circuit. It may be used in a wide range of
      applications and in complex media, including blood. These uses might include cell
      typing, the detection of large proteins, viruses, antibodies, DNA, electrolytes,
      drugs, pesticides and other low-molecular-weight compounds.

PMID- 9177345
TI  - Dissociating types of mental computation.
AB  - A fundamental issue in the study of cognition and the brain is the nature of
      mental computation. How far does this depend on internally represented systems of
      rules, expressed as strings of symbols with a syntax, as opposed to more
      distributed neural systems, operating subsymbolically and without syntax? The
      mental representation of the regular and irregular past tense of the English verb
      has become a crucial test case for this debate. Single-mechanism approaches argue
      that current multilayer connectionist networks can account for the learning and
      representation both of regular and of irregular forms. Dual-mechanism approaches,
      although accepting connectionist accounts for the irregular forms, argue that a
      symbolic, rule-based system is required to explain the properties of the regular
      past tense and, by extension, the properties of language and cognition in
      general. We show here that the regular and irregular past tense are supported by
      different neural systems, which can become dissociated by damage to the brain.
      This is evidence for functional and neurological distinctions in the types of
      mental computation that support these different aspects of linguistic and
      cognitive performance.

PMID- 9177346
TI  - Distortions of visuotopic map match orientation singularities in primary visual
      cortex.
AB  - The map of orientation columns in primary visual cortex (V1) is known to show
      strong local distortions, with a generally smooth progression of orientation
      preference across extended regions of cortex, interrupted by sharp jumps
      (fractures) and point singularities. The map of visual space on V1, in contrast,
      has been assumed to be locally smooth and isotropic. We find, on the contrary,
      that the map of visual space on cat V1 shows strong and systematic local
      distortions in register with inhomogeneities in the orientation map, with the
      rate of receptive field movement across cortex being largely proportional to the
      local rate of change of orientation. This suggests possible systematic local
      variations in the functional connectivity of short-range lateral connections that
      underlie local cortical processing.

PMID- 9177347
TI  - GABA in the mammalian suprachiasmatic nucleus and its role in diurnal
      rhythmicity.
AB  - Mammals manifest circadian behaviour timed by an endogenous clock in the
      hypothalamic suprachiasmatic nucleus (SCN). Considerable progress has been made
      in identifying the molecular basis of the circadian clock, but the mechanisms by
      which it is translated into cyclic firing activity, high during the day and low
      at night, are still poorly understood. GABA (gamma-aminobutyric acid), a common
      inhibitory neurotransmitter in the central nervous system, is particularly
      densely distributed within the SCN, where it is located in the majority of
      neuronal somata and synaptic terminals. Using an in vitro brain-slice technique,
      we have now studied the effect of bath-applied GABA on adult SCN neurons at
      various times of the day. We find that GABA acts as an inhibitory
      neurotransmitter at night, decreasing the firing frequency; but during the day
      GABA acts as an excitatory neurotransmitter, increasing the firing frequency. We
      show that this dual effect, which is mediated by GABA(A) receptors, may be
      attributed to an oscillation in intracellular chloride concentration. A likely
      explanation is that the amplitude of the oscillation in firing rate, displayed by
      individual neurons, is amplified by the dual effect of GABA in the SCN's
      GABAergic network.

PMID- 9177348
TI  - The Rx homeobox gene is essential for vertebrate eye development.
AB  - Development of the vertebrate eye requires a series of steps including
      specification of the anterior neural plate, evagination of the optic vesicles
      from the ventral forebrain, and the cellular differentiation of the lens and
      retina. Homeobox-containing genes, especially the transcription regulator Pax6,
      play a critical role in vertebrate and invertebrate eye formation. Mutations in
      Pax6 function result in eye malformations known as Aniridia in humans and Small
      eye syndrome in mice. The Drosophila homologue of Pax6, eyeless, is also
      necessary for correct invertebrate eye development, and its misexpression leads
      to formation of ectopic eyes in Drosophila. Here we show that a conserved
      vertebrate homeobox gene, Rx, is essential for normal eye development, and that
      its misexpression has profound effects on eye morphology. Xenopus embryos
      injected with synthetic Rx RNA develop ectopic retinal tissue and display
      hyperproliferation in the neuroretina. Mouse embryos carrying a null allele of
      this gene do not form optic cups and so do not develop eyes. The Rx gene family
      plays an important role in the establishment and/or proliferation of retinal
      progenitor cells.

PMID- 9177349
TI  - The putative chaperone calmegin is required for sperm fertility.
AB  - The proper folding of newly synthesized membrane proteins in the endoplasmic
      reticulum (ER) is required for the formation of functional mature proteins.
      Calnexin is a ubiquitous ER chaperone that plays a major role in quality control
      by retaining incompletely folded or misfolded proteins. In contrast to other
      known chaperones such as heat-shock proteins, BiP and calreticulin, calnexin is
      an integral membrane protein. Calmegin is a testis-specific ER protein that is
      homologous to calnexin. Here we show that calmegin binds to nascent polypeptides
      during spermatogenesis, and have analysed its physiological function by targeted
      disruption of its gene. Homozygous-null male mice are nearly sterile even though
      spermatogenesis is morphologically normal and mating is normal. In vitro, sperm
      from homozygous-null males do not adhere to the egg extracellular matrix (zona
      pellucida), and this defect may explain the observed infertility. These results
      suggest that calmegin functions as a chaperone for one or more sperm surface
      proteins that mediate the interactions between sperm and egg. The defective zona
      pellucida-adhesion phenotype of sperm from calmegin-deficient mice is reminiscent
      of certain cases of unexplained infertility in human males.

PMID- 9177350
TI  - Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.
AB  - Chemokines are small secreted proteins that stimulate the directional migration
      of leukocytes and mediate inflammation. During screening of a murine choroid
      plexus complementary DNA library, we identified a new chemokine, designated
      neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern,
      Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein. Full-length
      recombinant neurotactin is localized on the surface of transfected 293 cells.
      Recombinant neurotactin containing the chemokine domain is chemotactic for
      neutrophils both in vitro and in vivo. Neurotactin messenger RNA is predominantly
      expressed in normal murine brain and its protein expression in activated brain
      microglia is upregulated in mice with experimental autoimmune encephalomyelitis,
      as well as in mice treated with lipopolysaccharide. Distinct from all other
      chemokine genes, the neurotactin gene is localized to human chromosome 16q.
      Consequently we propose that neurotactin represents a new delta-chemokine family
      and that it may play a role in brain inflammation processes.

PMID- 9177351
TI  - Ligand-specific oligomerization of T-cell receptor molecules.
AB  - T cells initiate many immune responses through the interaction of their T-cell
      antigen receptors (TCR) with antigenic peptides bound to major histocompatibility
      complex (MHC) molecules. This interaction sends a biochemical signal into the T
      cell by a mechanism that is not clearly understood. We have used quasielastic
      light scattering (QELS) to show that, in the presence of MHC molecules bound to a
      full agonist peptide, TCR/peptide-MHC complexes oligomerize in solution to form
      supramolecular structures at concentrations near the dissociation constant of the
      binding reaction. The size of the oligomers is concentration dependent and is
      calculated to contain two to six ternary complexes for the concentrations tested
      here. This effect is specific as neither molecule forms oligomers by itself, nor
      were oligomers observed unless the correct peptide was bound to the MHC. These
      results provide direct evidence for models of T-cell signalling based on the
      specific assembly of multiple TCR/peptide-MHC complexes in which the degree of
      assembly determines the extent and qualitative nature of the transduced signal.
      They may also explain how T cells maintain sensitivity to antigens present in
      only low abundance on the antigen-presenting cell.

PMID- 9177352
TI  - A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis.
AB  - Leukotriene B4 (LTB4) is a potent chemoattractant that is primarily involved in
      inflammation, immune responses and host defence against infection. LTB4 activates
      inflammatory cells by binding to its cell-surface receptor (BLTR). LTB4 can also
      bind and activate the intranudear transcription factor PPAR alpha, resulting in
      the activation of genes that terminate inflammatory processes. Here we report the
      cloning of the complementary DNA encoding a cell-surface LTB4 receptor that is
      highly expressed in human leukocytes. Using a subtraction strategy, we isolated
      two cDNA clones (HL-1 and HL-5) from retinoic acid-differentiated HL-60 cells.
      These two clones contain identical open reading frames encoding a protein of 352
      amino acids and predicted to contain seven membrane-spanning domains, but
      different 5'-untranslated regions. Membrane fractions of Cos-7 cells transfected
      with an expression construct containing the open reading frame of HL-5 showed
      specific LTB4 binding, with a K(d) (0.154nM) comparable to that observed in
      retinoic acid-differentiated HL-60 cells. In CHO cells stably expressing this
      receptor, LTB4 induced increases in intracellular calcium, D-myo-inositol-1,4,5
      triphosphate (InsP3) accumulation, and inhibition of adenylyl cyclase.
      Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic
      responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive
      manner. Our findings, together with previous reports, show that LTB4 is a unique
      lipid mediator that interacts with both cell-surface and nuclear receptors.

PMID- 9177353
TI  - The three-dimensional structure of aquaporin-1.
AB  - The entry and exit of water from cells is a fundamental process of life.
      Recognition of the high water permeability of red blood cells led to the proposal
      that specialized water pores exist in the plasma membrane. Expression in Xenopus
      oocytes and functional studies of an erythrocyte integral membrane protein of
      relative molecular mass 28,000, identified it as the mercury-sensitive water
      channel, aquaporin-1 (AQP1). Many related proteins, all belonging to the major
      intrinsic protein (MIP) family, are found throughout nature. AQP1 is a
      homotetramer containing four independent aqueous channels. When reconstituted
      into lipid bilayers, the protein forms two-dimensional lattices with a unit cell
      containing two tetramers in opposite orientation. Here we present the three
      dimensional structure of AQP1 determined at 6A resolution by cryo-electron
      microscopy. Each AQP1 monomer has six tilted, bilayer-spanning alpha-helices
      which form a right-handed bundle surrounding a central density. These results,
      together with functional studies, provide a model that identifies the aqueous
      pore in the AQP1 molecule and indicates the organization of the tetrameric
      complex in the membrane.

PMID- 9177354
TI  - Three-dimensional organization of a human water channel.
AB  - Aquaporins (AQP) are members of the major intrinsic protein (MIP) superfamily of
      integral membrane proteins and facilitate water transport in various eukaryotes
      and prokaryotes. The archetypal aquaporin AQP1 is a partly glycosylated water
      selective channel that is widely expressed in the plasma membranes of several
      water-permeable epithelial and endothelial cells. Here we report the three
      dimensional structure of deglycosylated, human erythrocyte AQP1, determined at 7
      A resolution in the membrane plane by electron crystallography of frozen-hydrated
      two-dimensional crystals. The structure has an inplane, intramolecular 2-fold
      axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer
      is composed of six membrane-spanning, tilted alpha-helices. These helices form a
      barrel that encloses a vestibular region leading to the water-selective channel,
      which is outlined by densities attributed to the functionally important NPA boxes
      and their bridges to the surrounding helices. The intramolecular symmetry within
      the AQP1 molecule represents a new motif for the topology and design of membrane
      protein channels, and is a simple and elegant solution to the problem of
      bidirectional transport across the bilayer.

PMID- 9177356
TI  - Changes in The Journal of Clinical Endocrinology and Metabolism--an editorial
      from Dr. Maria I. New, Editor-in-Chief.

PMID- 9177355
TI  - Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2.
AB  - The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of
      cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer
      alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with
      major histocompatibility complex (MHC) class I/peptide by binding to the class I
      molecule. Here we report the crystal structure at 2.7 A resolution of a complex
      between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated
      with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with
      the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin.
      A flexible loop of the alpha3 domain (residues 223-229) is clamped between the
      complementarity-determining region (CDR)-like loops of the two CD8 subunits in
      the classic manner of an antibody-antigen interaction, precluding the binding of
      a second MHC molecule. The position of the alpha3 domain is different from that
      in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex,
      but no conformational change extends to the MHC/peptide surface presented for TCR
      recognition. Although these shifts in alpha3 may provide a synergistic modulation
      of affinity, the binding of CD8 to MHC is clearly consistent with an avidity
      based contribution from CD8 to TCR-peptide-MHC interactions.

PMID- 9177357
TI  - The critical role of alcohol consumption in determining the risk of breast cancer
      with postmenopausal estrogen administration.

PMID- 9177358
TI  - Age-associated sarcopenia--issues in the use of testosterone as an anabolic agent
      in older men.

PMID- 9177359
TI  - Testosterone replacement in older hypogonadal men: a 12-month randomized
      controlled trial.
AB  - A decline in testicular function is recognized as a common occurrence in older
      men. However data are sparse regarding the effects of hypogonadism on age
      associated physical and cognitive declines. This study was undertaken to examine
      the year-long effects of testosterone administration in this patient population.
      Fifteen hypogonadal men (mean age 68 +/- 6 yr) were randomly assigned to receive
      a placebo, and 17 hypogonadal men (mean age 65 +/- 7 yr) were randomly assigned
      to receive testosterone. Hypogonadism was defined as a bioavailable testosterone
      <60 ng/dL. The men received injections of placebo or 200 mg testosterone
      cypionate biweekly for 12 months. The main outcomes measured included grip
      strength, hemoglobin, prostate-specific antigen, leptin, and memory. Testosterone
      improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P
      < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in
      leptin than those assigned to the control group (mean +/- SEM: -2.0 +/- 0.9 ng/dL
      vs. 0.8 +/- 0.7 ng/dL; P < 0.02). There were no significant changes in prostate
      specific antigen or memory. Three subjects receiving placebo and seven subjects
      receiving testosterone withdrew from the study. Three of those seven withdrew
      because of an abnormal elevation in hematocrit. Testosterone supplementation
      improved strength, increased hemoglobin, and lowered leptin levels in older
      hypogonadal men. Testosterone may have a role in the treatment of frailty in
      males with hypogonadism; however, older men receiving testosterone must be
      carefully monitored because of its potential risks.

PMID- 9177360
TI  - A decade of the Massachusetts General Hospital Neuroendocrine Clinical Center.

PMID- 9177361
TI  - Genetic basis of endocrine disease: pituitary tumor pathogenesis.

PMID- 9177362
TI  - Clinical review 88: hypoglycemia unawareness in noninsulin-dependent diabetes
      mellitus.

PMID- 9177363
TI  - Leptin is normal in PCOS, an editorial about three "negative" papers.

PMID- 9177364
TI  - Leptin concentrations in the polycystic ovary syndrome.
AB  - The polycystic ovary syndrome (PCOS) is characterized by menstrual disturbances,
      chronic anovulation and hyperandrogenism and is associated with insulin
      resistance and hyperinsulinemia. Leptin, the product of the ob gene, is an
      adipocyte-secreted molecule that signals the magnitude of energy stores to the
      brain and has been recently shown to have important effects on the reproductive
      axis of rodents. To assess the potential contribution of leptin to the
      pathogenesis of PCOS, we measured leptin levels in 24 obese women with PCOS and
      12 weight- and age-matched controls and determined whether alterations in
      hyperinsulinemia produced by administration of the insulin-sensitizing agent
      troglitazone had an effect on serum leptin levels. Leptin concentrations at
      baseline were not different in women with PCOS (38.1 +/- 2.15 ng/mL) and controls
      (33.12 +/- 2.39 ng/mL). Moreover, leptin concentrations remained unchanged after
      treatment with troglitazone (38.1 +/- 2.15 vs. 39.21 +/- 2.65 ng/mL). Baseline
      leptin correlated strongly with body mass index in both controls (r = 0.59; P <
      0.05) and women with PCOS (r = 0.70; P = 0.0004). Leptin levels were not
      associated with baseline insulin, testosterone, non-sex hormone-binding globulin
      (SHBG)-bound testosterone, dehydroepiandrosterone sulfate, estradiol, or SHBG.
      Finally, despite significantly reduced insulin, non-SHBG-bound testosterone, and
      estradiol levels after troglitazone treatment of women with PCOS, their leptin
      levels remained unchanged. We conclude that circulating leptin levels in patients
      with PCOS do not differ from those in age- and weight-matched controls.
      Furthermore, increased circulating insulin due to insulin resistance does not
      appear to alter circulating leptin levels in women with PCOS.

PMID- 9177365
TI  - Serum leptin levels in women with polycystic ovary syndrome: the role of insulin
      resistance/hyperinsulinemia.
AB  - Polycystic ovary syndrome (PCOS) is associated with chronic anovulation,
      hyperandrogenemia, insulin resistance (IR)/hyperinsulinemia, and a high incidence
      of obesity. Thus, PCOS serves as a useful model to assess the role of IR and
      chronic endogenous insulin excess on leptin levels. Thirty-three PCOS and 32
      normally cycling (NC) women of similar body mass index (BMI) were studied.
      Insulin sensitivity (S(I)) was assessed by rapid ivGTT in a subset of 28 PCOS and
      29 NC subjects; percent body fat was determined by dual-energy x-ray
      absorptiometry (DEXA) in 14 PCOS and 17 NC. Fasting (0800 h) and 24-h mean hourly
      insulin levels were 2-fold higher (P < 0.0001), and S(I) was 50% lower (P =
      0.005) in PCOS than in NC, while serum androstenedione (A), testosterone (T), 17
      alpha hydroxyprogesterone (17OHP), and estrone (E1) levels were elevated (P <
      0.0001), and sex hormone-binding globulin (SHBG) levels were decreased (P <
      0.01). Twenty-four hour LH pulse frequency, mean pulse amplitude, and mean LH
      levels were elevated in PCOS (P < 0.001) as compared with NC. Serum leptin levels
      for PCOS (24.1 +/- 2.6 ng/mL) did not differ from NC (21.5 +/- 3.5 ng/mL) and
      were positively correlated with BMI (r = 0.81) and percent body fat (r = 0.91)
      for the two groups (both P < 0.0001). Leptin levels for PCOS and NC correlated
      positively with fasting and 24-h mean insulin levels (r = 0.81, P < 0.0001 for
      both PCOS and NC) and negatively with S(I) and SHBG levels. Leptin concentrations
      for PCOS, but not NC, correlated positively with 24-h mean glucose levels and
      inversely with 24-h mean LH levels and 24-h mean LH pulse amplitude. Leptin
      levels were not correlated with estrogen or androgen levels for either PCOS or
      NC, although leptin levels were positively related to the ratios of E1/SHBG and
      E2/SHBG for both PCOS and NC and to the ratio of T/SHBG for PCOS only. In
      stepwise multivariate regression with forward selection, only 24-h mean insulin
      levels contributed significantly (P < 0.01) to leptin levels independent of BMI
      and percent body fat for both PCOS and NC. Given this relationship and the
      presence of 2-fold higher 24-h mean insulin levels in PCOS, the expected
      elevation of leptin levels in PCOS was not found. This paradox may be explained
      by the presence of adipocyte IR specific to PCOS, which may negate the
      stimulatory impact of hyperinsulinemia on leptin secretion, a proposition
      requiring further study.

PMID- 9177366
TI  - Serum leptin concentrations in women with polycystic ovary syndrome.
AB  - The role of gonadotropins, androgens, and insulin in the regulation of
      circulating leptin levels is obscure. In order to clarify the relationships of
      these parameters we studied serum leptin levels in 19 healthy control subjects
      and in 35 hyperandrogenic and hyperinsulinemic patients with polycystic ovary
      syndrome (PCOS). Serum leptin concentrations did not differ significantly between
      PCOS patients and control subjects. When PCOS and control groups were analyzed
      together by univariate analysis, serum leptin was positively correlated with body
      mass index (BMI), body weight, serum insulin, serum triglyceride, and serum free
      testosterone concentrations. Serum leptin was inversely correlated with serum sex
      hormone binding globulin (SHBG) concentrations. There were no significant
      correlations between serum leptin and testosterone, androstenedione, or
      gonadotropin concentrations. Serum insulin, triglyceride, and free testosterone
      concentrations were positively correlated, and serum SHBG was negatively
      correlated with BMI. However, when BMI on one hand and serum insulin,
      triglyceride, free testosterone, or SHBG on other hand were used as independent
      variables in the partial correlation analysis with leptin, BMI turned out to be
      the variable primarily responsible for all of the correlations with leptin. In
      conclusion, the concept that circulating leptin levels would be different in PCOS
      patients than in regularly menstruating control subjects is not supported by our
      data.

PMID- 9177367
TI  - The hypothyroxinemia [corrected] of prematurity.

PMID- 9177368
TI  - Neonatal hypothyroxinemia: effects of iodine intake and premature birth.
AB  - We have investigated the effects of iodine (I) intake on urinary I excretion in
      preterm (PT) babies up to 2 months after birth and its effect on serum T4, free
      T4 (FT4), T3, TSH, and thyroglobulin (Tg) levels compared to those in term (T)
      newborns. Very premature and very sick infants were in negative I balance for the
      first weeks after birth. Later, these same infants, as well as the other PT and T
      newborns, were in positive balance; 75- 80% of the ingested I was not accounted
      for in the urine. The urinary I levels of PT and T neonates cannot be equated to
      their I intakes. T4, FT4, and T3 levels in PT and T neonates increased with
      postmenstrual age, whereas Tg decreased and TSH did not change. Serum FT4, T3,
      Tg, and TSH levels in PT neonates were affected negatively, independently from
      age, by a low I intake. PT birth also affected T4, FT4, and Tg negatively,
      independently from I intake and postmenstrual age, for at least 6-8 weeks after
      birth. Care should be taken to avoid I deficiency in PT neonates. However, even
      when I intake is adequate, PT newborns are hypothyroxinemic compared to T babies
      during an important period of brain development. This suggests the possible
      convenience of interventions that might mimic the intrauterine hormone
      environment and accelerate maturation.

PMID- 9177369
TI  - Resistance to neuroglycopenia: an adaptive response during intensive insulin
      treatment of diabetes.
AB  - Counterregulation and awareness of hypoglycemia begins at lower plasma glucose
      levels in insulin-dependent diabetes mellitus (IDDM) subjects given intensive
      insulin treatment. To determine whether these changes are associated with an
      alteration in the susceptibility of the brain to mild hypoglycemia, we compared
      central nervous system responses to hypoglycemia in 8 intensively treated
      (hemoglobin A1, 8.3 +/- 0.2%; normal, <8%) and 11 conventionally treated IDDM
      patients (hemoglobin A1, 14.6 +/- 1.3%) with those in 10 healthy subjects. Plasma
      glucose was lowered from approximately 4.6 mmol/L in 0.5-0.6 steps using the
      clamp technique. Glucose levels triggering hormonal responses and perception of
      hypoglycemic symptoms were significantly lower in intensively treated patients
      compared to their poorly controlled counterparts (P < 0.05), and hormonal
      responses were suppressed compared to those in healthy controls. Similarly
      directed changes occurred in the level of circulating glucose required to alter
      cortical evoked potentials during hypoglycemia. A greater reduction in plasma
      glucose was required to alter P300 event-related potentials in the intensively
      treated patients (2.2 mmol/L) compared to those in the conventionally treated and
      nondiabetic groups (approximately 3.5 and approximately 3.0 mmol/L,
      respectively). We conclude that intensively treated IDDM patients are resistant
      to changes in cortical evoked potentials induced by mild hypoglycemia. This may
      explain why intensively treated IDDM counterregulate and experience hypoglycemic
      symptoms at a lower glucose level than conventionally treated patients.

PMID- 9177370
TI  - Predictors of early remission of hyperthyroidism in children.
AB  - Children with hyperthyroidism often require prolonged courses of antithyroid
      medication to achieve remission, and long-term compliance is problematic. To
      determine which clinical and laboratory features predict early remission, we
      reviewed the records of 191 patients less than 19 yr old with Graves' disease. We
      compared patients achieving remission within 2 yr (group 1, n = 27) with those
      who completed more than 2 yr of medical therapy but did not achieve a remission
      (group 2, n = 79). Patients who were in neither of the above categories (n = 85)
      were excluded from the statistical analysis. Variables that were measurable at
      the time of diagnosis, recorded in more than 50% of the study population and
      associated with early remission in the univariate analysis (P < or = 0.05), were
      entered into a stepwise multiple logistic regression analysis. Variables
      retaining a significant association with early remission (P < 0.05) were
      considered independent predictors of early remission. Patients achieving early
      remission were older (mean, 12.5 vs. 10.9 yr, P = 0.039) and had higher body mass
      indexes (BMI, 19.0 vs. 16.6, P = 0.002), higher BMI SD scores (-0.03 vs. -0.60, P
      = 0.004), lower heart rates (110 vs. 121, P = 0.023), smaller goiters (group 1:
      60% with moderate/large goiter; group 2: 83%, P = 0.050), lower platelet counts
      (272 vs. 339 K/microL, P = 0.006), lower serum T4 and T3 concentrations at
      presentation (T4: 18.3 vs. 22.5 microg/dL, P = 0.015; T3: 439 vs. 613 ng/dL, P =
      0.008), and were less likely to have a positive test for thyroid stimulating Igs
      (group 1: 50% vs. group 2: 93%, P = 0.008). Regression analysis identified BMI SD
      score and goiter size as independent predictors of early remission (P < 0.05).
      Eighty-six percent of patients with BMI SD score above -0.5 SD and minimal/small
      goiters achieved early remission, compared with 13% of those with BMI SD score
      below -0.5 SD and moderate/large goiters. We conclude that, of multiple clinical
      and laboratory variables associated with early remission, BMI SD score and goiter
      size are independent predictors. Algorithms employing these two variables can be
      used to facilitate counseling of patients and expedite therapeutic decisions.

PMID- 9177371
TI  - Fifty years of experience with propylthiouracil-associated hepatotoxicity: what
      have we learned?
AB  - The aim of this study was to determine the optimal management of patients with
      propylthiouracil (PTU) hepatotoxicity. A MEDLINE search for English language
      cases of PTU hepatotoxicity between 1966 and April 1996 was performed, and
      additional cases were cross-referenced. Twenty-seven cases were selected based on
      the availability of information on patient management after the onset of
      hepatotoxicity. Eighty-five percent of the selected cases met this criterion. A
      detailed summary of the management of two cases of PTU hepatotoxicity at our
      institutions is also provided. Although most patients recovered once PTU was
      stopped, seven patients died. Patients with PTU hepatotoxicity who survived were
      more likely to have received 131I during the course of their illness than those
      who died (P < 0.03, by Fisher's exact test). In our two patients,
      hyperbilirubinemia was linearly associated with progressively decreasing T4
      levels (r = 0.91; P < 0.001) despite the presence of clinical thyrotoxicosis in
      one of the patients. These findings demonstrate the need for appropriate clinical
      evaluation and treatment of thyroid disease during the course of hepatotoxicity.
      Additionally, we report the first pediatric patient with PTU hepatotoxicity to
      undergo liver transplantation. The emerging role of liver transplantation in
      these patients is discussed.

PMID- 9177372
TI  - Blood pressure in children and adolescents with Cushing's syndrome before and
      after surgical care.
AB  - Approximately half of children and adolescents with Cushing's syndrome develop
      hypertension. To examine the role of hypercortisolism in the pathogenesis of
      hypertension in young patients and to establish its reversibility, we studied 31
      hypertensive children and adolescents with Cushing's syndrome (systolic,
      diastolic, and/or mean blood pressure more than 2 SD U for age and sex) from a
      total of 63 patients before, and for a period of 1 yr after surgical cure.
      Preoperatively, 93.5%, 42%, and 45% of these patients presented with an increase
      of the systolic, diastolic, and mean blood pressure, respectively. The systolic
      blood pressure remained increased in 30.7%, 15.8%, and 5.5% of patients at 3, 6,
      and 12 months after surgical cure, respectively. The diastolic and mean blood
      pressure completely normalized by 3 months after surgical cure. A significant,
      positive correlation was observed between the systolic blood pressure and the
      duration of the disease, but no correlation was seen with the 24-h urinary free
      cortisol values and/or the patients' body mass indices. The lack of correlation
      between 24-h urinary free cortisol values and blood pressure suggests that
      hypercortisolism influences blood pressure through multiple pathways. The
      positive correlation between the systolic blood pressure and the duration of the
      disease points towards the deleterious effects of prolonged hypercortisolism and
      the significance of early diagnosis and treatment. The fact that the blood
      pressure normalized within a year from the correction of hypercortisolism
      suggests that, as a rule, young patients with hypercortisolism do not develop
      essential hypertension.

PMID- 9177373
TI  - Aromatase deficiency in a female who is compound heterozygote for two new point
      mutations in the P450arom gene: impact of estrogens on hypergonadotropic
      hypogonadism, multicystic ovaries, and bone densitometry in childhood.
AB  - We report on a female who is compound heterozygote for two new point mutations in
      the CYP19 gene. The allele inherited from her mother presented a base pair
      deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results
      in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele
      inherited from her father showed a point mutation from G-->A at the splicing
      point (canonical GT to mutational AT) between exon and intron 3. This mutation
      ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase
      deficiency was already suspected because of the marked virilization occurring
      prepartum in the mother, and the diagnosis was confirmed shortly after birth.
      Extremely low levels of serum estrogens were found in contrast to high levels of
      androgens. Ultrasonographic follow-up studies revealed persistently enlarged
      ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous
      large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles
      already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels
      remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day)
      given for 50 days at the age of 3 6/12 yr resulted in normalization of serum
      gonadotropin levels, regression of ovarian size, and increase of whole body and
      lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size
      returned to pretreatment levels shortly (150 days) after cessation of E2 therapy.
      Therefore, we recommend that affected females be treated with low-dose E2 in
      amounts sufficient to result in physiological prepubertal E2 concentrations using
      an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted
      throughout childhood and puberty to ensure normal skeletal maturation and
      adequate adolescent growth spurt, normal accretion of bone mineral density, and,
      at the appropriate age, female secondary sex maturation.

PMID- 9177374
TI  - Long-term suppression of testosterone after treatment with a gonadotropin
      releasing hormone agonist in a woman with a presumed testosterone secreting
      ovarian tumor.

PMID- 9177375
TI  - Iatrogenic [corrected] extrapontine myelinolysis in central diabetes insipidus:
      are cyclosporine and 1-desamino-8-D-arginine vasopressin harmful in association?

PMID- 9177376
TI  - Tibolone: influence on markers of cardiovascular disease.
AB  - Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic
      properties relieves climacteric symptoms and prevents postmenopausal bone loss.
      The influence of tibolone treatment on coagulation, fibrinolysis, and lipid
      metabolism was investigated in 91 healthy late postmenopausal women. They were
      randomly assigned in a double-blind, placebo-controlled 2-year study to receive
      either tibolone 1.25 mg (n = 36, 29 completed) or 2.5 mg (n = 35, 28 completed)
      or placebo (n = 20, 13 completed). The biochemical markers of lipid metabolism,
      fibrinolysis, and coagulation were measured every 3 months. In both tibolone
      groups a similar (approximately 30%) decrease in high density lipoprotein
      cholesterol and a corresponding lowering of apolipoprotein A-1 (P < 0.001) was
      detected. Also serum total cholesterol and triglycerides were reduced
      (approximately 15%; P < 0.01), whereas low density lipoprotein cholesterol,
      apolipoprotein B, and lipoprotein(a) were unaffected by tibolone. The two dose
      levels of tibolone resulted in a similar, marked lowering (approximately 30%) of
      tissue plasminogen activator and plasminogen activator inhibitor activity as
      compared with placebo (P < 0.001). Plasminogen increased (approximately 15%; P <
      0.001) in both groups. Fibrinogen was lowered (P < 0.01) in the low-dose group,
      and antithrombin III remained unchanged. The overall effect on hemostatic factors
      of the present doses of tibolone in healthy, late postmenopausal women tends
      towards increased fibrinolysis and unchanged coagulation. This may be beneficial
      and might theoretically counterbalance the potentially negative effect of the
      decrease in high density lipoprotein cholesterol.

PMID- 9177377
TI  - Increased serum concentration of soluble CD30 in patients with Graves' disease
      and Hashimoto's thyroiditis.
AB  - This study investigated serum levels of the soluble form of CD30 (sCD30), which
      is mainly secreted from T helper 2(Th2) cells, in autoimmune thyroid diseases.
      The possible relationship of sCD30 to autoantibody production was also evaluated.
      Serum levels of sCD30 were determined by an enzyme-linked immunosorbent assay in
      71 patients with Graves' disease, 37 patients with Hashimoto's thyroiditis, and
      21 normal donors. Compared with normal subjects (7.1 +/- 4.5 U/mL), sCD30 was
      increased in patients with Graves' disease (29.2 +/- 25.2 U/mL, P < 0.0001) and
      in patients with Hashimoto's thyroiditis (29.9 +/- 26.9 U/mL, P < 0.0001). In
      Graves' disease, sCD30 levels were higher in thyrotoxic patients (41.7 +/- 31.2
      U/mL, P < 0.001) than in remission patients (15.8 +/- 11.0 U/mL), and a
      significant correlation was observed between sCD30 levels and serum activities of
      TSH receptor antibody (r = 0.444, P < 0.0001). In Hashimoto's thyroiditis, sCD30
      levels were higher in patients with transient destructive thyrotoxicosis caused
      by the aggravation of the disease (48.8 +/- 34.4 U/mL, P < 0.05) than in
      euthyroid patients (24.2 +/- 19.4 U/mL). These data suggest that serum sCD30 is a
      valuable marker of disease activity and support an important role of the Th2-type
      immune response in the pathogenesis in Graves' disease and Hashimoto's
      thyroiditis.

PMID- 9177378
TI  - Altered ionic effects of insulin in hypertension: role of basal ion levels in
      determining cellular responsiveness.
AB  - To investigate the ionic actions of insulin in hypertension, 19F- and 31P-nuclear
      magnetic resonance spectroscopy were used to measure cytosolic free calcium
      (Ca(i)) and intracellular free magnesium (Mg(i)) levels in red blood cells from
      normal (n = 9) and hypertensive (n = 9) subjects before and 30, 60, 120, and 180
      min after in vitro incubation with insulin. In hypertensive patients, basal Ca(i)
      levels were significantly higher (30.0 +/- 2.2 vs. 19.8 +/- 2.5 nmol/L; P <
      0.05), and basal Mg(i) levels were significantly lower (170 +/- 10.9 vs. 209 +/-
      8 micromol/L; P < 0.05) than in normotensive subjects. In normal cells, insulin
      significantly elevated Ca(i) to 39.8 +/- 8.0, 50.1 +/- 8.2, 69.3 +/- 11.1, and
      50.9 +/- 13.4 nmol/L at 30, 60, 120, and 180 min and Mg(i) to 238 +/- 10,264 +/-
      14,226 +/- 11, and 216 +/- 10 micromol/L at 30, 60, 120, and 180 min. In
      hypertensive subjects, the insulin-dependent Ca(i) elevation was blunted, and
      Mg(i) accumulation was completely suppressed. Continuous relationships were
      observed between basal values of each ion and insulin responses; the greater the
      Ca(i), the less the Ca(i) rose (r = -0.574; P = 0.013), and the lower the Mg(i),
      the less Mg(i) rose (r = 0.524; P = 0.025). Furthermore, a blunting of Mg(i)
      responses to insulin could be reproduced in normal cells that were magnesium
      depleted by prior treatment either with A23187 in a calcium-free medium or with
      high glucose concentrations (15 mmol/L). Once again, insulin responsiveness
      followed basal Mg(i) levels (r = 0.637; P < 0.001). Together, these data
      demonstrate ionic aspects of insulin resistance in hypertension and suggest that
      Ca(i) and Mg(i) levels may regulate cellular responsiveness to insulin. This may
      help to explain the different vascular actions attributed to insulin in normal
      compared with insulin-resistant states such as hypertension.

PMID- 9177379
TI  - Ribonucleic acid expression of the clustered imprinted genes, p57KIP2, insulin
      like growth factor II, and H19, in adrenal tumors and cultured adrenal cells.
AB  - The recently cloned cyclin-dependent kinase inhibitor gene p57KIP2 is genomically
      imprinted and located on human chromosome 11p15.5. This region contains two other
      imprinted genes, insulin-like growth factor II (IGF-II) and H19, both of which
      seem to be implicated in adrenal neoplasms. We analyzed the expression of the
      putative tumor suppressor p57KIP2 gene by Northern blotting in normal and
      hyperplastic adrenals, adrenocortical tumors, and pheochromocytomas. The
      expression of p57KIP2 messenger ribonucleic acid (mRNA) correlated positively
      with H19 and negatively with IGF-II RNA in adrenocortical tissues. p57KIP2 mRNA
      (and H19 RNA) was abundantly expressed in normal human adrenals, adrenocortical
      adenomas from patients with Cushing's or Conn's syndrome or without clinical
      evidence of hormone overproduction, hyperplastic adrenals, and tumor-adjacent
      adrenal tissues, in which IGF-II mRNA expression was low. In most adrenocortical
      carcinomas and virilizing adrenal adenomas, very low levels of both p57KIP2 and
      H19 RNAs were observed, whereas IGF-II was highly expressed. In
      pheochromocytomas, p57KIP2 and H19 RNA expression was highly variable, but on the
      average it was about 45% and 27%, respectively, of that in normal and tumor
      adjacent adrenals. In cultured adrenocortical cells, ACTH and dibutyryl cAMP
      treatment slightly reduced the predominant 1.7-kilobase (kb) transcript of
      p57KIP2 gene, but induced a 2.5-kb transcript with a simultaneous increase in H19
      RNA expression. The stimulatory effect of ACTH on the 2.5-kb p57KIP2 and H19
      transcript accumulation was enhanced by exogenous IGF-II and IGF-I. Our data show
      that p57KIP2 and H19 RNAs are expressed usually in parallel in normal and
      pathological adrenocortical tissues. The decreased expression of both p57KIP2 and
      H19 RNAs in conjunction with elevated IGF-II mRNA expression in hormonally active
      adrenocortical carcinomas suggests that the loss of expression of the putative
      tumor suppressor genes p57KIP2 and H19 may be involved in the pathogenesis of
      these neoplasms.

PMID- 9177380
TI  - Vitamin D receptor polymorphisms correlate to parathyroid cell function in
      primary hyperparathyroidism.
AB  - Calcitriol acts via its receptor (VDR) and inhibits PTH secretion and parathyroid
      cell proliferation. Increased prevalence of the polymorphic VDR alleles b, a, and
      T has been demonstrated in sporadic primary hyperparathyroidism. Sixty-two
      patients with primary hyperparathyroidism due to parathyroid adenoma (mean age,
      69.5 +/- 1.4 yr) were genotyped for these VDR polymorphisms. Dispersed cells of
      the adenomas were exposed to increasing concentrations of extracellular Ca2+ and
      analyzed for PTH release and cytoplasmic Ca2+ concentrations. Ca2+-mediated PTH
      inhibition exhibited higher ED50 and less suppression in the cells of patients
      who were homozygous for the b, a, and T alleles (P < 0.05-0.10). When analyzing
      haplotypes, the patients with baT demonstrated a ED50 of 1.81 +/- 0.15 vs. 1.29
      +/- 0.10 for BAt (P < 0.05). As VDR alleles were unrelated to parathyroid
      intracellular Ca2+, influences of polymorphic VDR alleles on PTH secretion seem
      to involve mechanisms other than the Ca2+-sensing protein of the parathyroid cell
      surface.

PMID- 9177381
TI  - Intraoperative adrenocorticotropin levels during transsphenoidal surgery for
      Cushing's disease do not predict cure.
AB  - Recently, intraoperative rapid immunochemiluminometric assay (ICMA) ACTH
      measurements have been used to evaluate the completeness of resection of ectopic
      ACTH-secreting tumors. This study evaluates whether this method can be applied to
      patients undergoing transsphenoidal surgery (TSS) for Cushing's disease to
      predict complete pituitary tumor resection. Eighteen patients with Cushing's
      disease undergoing TSS had plasma ACTH concentrations measured by a standard ICMA
      every 10 min for 1 h immediately after pituitary tumor removal. Patients were
      evaluated postoperatively for cure by standard criteria. ACTH levels were
      evaluated for percentage decrease from baseline at each time point. Patients who
      were cured (n = 11) had statistically greater decreases in ACTH levels (mean
      decrease 54%) than patients who were not (n = 7; 26% mean decrease, P < 0.04). By
      Receiver-Operator Characteristic (ROC) analysis, a reduction of at least 40% best
      predicted which patients were cured and which were not cured. This level of
      reduction was observed in 82% of cured patients, and a reduction of less than 40%
      was observed in 71% of those not cured. The analysis misclassified 4 of the 18
      patients, resulting in a diagnostic accuracy of 78%. Although the mean maximal
      decrease in ACTH concentrations after tumor removal was significantly different
      between cured and not cured patients with Cushing's disease, it was less dramatic
      than results in the previous ectopic ACTH study. This may relate to incomplete
      suppression and/or surgical manipulation of normal pituitary corticotrophs in
      patients with pituitary disease. In summary, in contrast to the ectopic ACTH
      syndrome, decline of plasma ACTH during TSS does not accurately predict complete
      tumor resection.

PMID- 9177382
TI  - Effectiveness versus efficacy: the limited value in clinical practice of high
      dose dexamethasone suppression testing in the differential diagnosis of
      adrenocorticotropin-dependent Cushing's syndrome.
AB  - High dose dexamethasone suppression testing has been widely employed in the
      differentiation between pituitary ACTH-dependent hypercortisolism [Cushing's
      disease (CD)] and the ectopic ACTH syndrome. We hypothesized that the high dose
      dexamethasone suppression test as it is performed in practice does not improve
      the ability to differentiate between these two types of ACTH-dependent Cushing's
      syndrome. Cases were drawn from 112 consecutive patients with ACTH-dependent
      Cushing's syndrome, who were then classified based upon results of inferior
      petrosal sinus sampling for ACTH levels. Analysis of test characteristics of high
      dose dexamethasone suppression testing was performed in the 73 patients for whom
      results are available. Statistical modeling was performed using the 68 cases with
      complete data on all assessed variables. Logistic regression models were used to
      predict the probability of pituitary-dependent Cushing's syndrome (CD) given the
      results of high dose dexamethasone suppression testing before and after
      adjustment for the contribution of a series of potential covariates. Of the 112
      patients with ACTH-dependent Cushing's syndrome, 15.2% had the ectopic ACTH
      syndrome, and the remainder had pituitary-dependent Cushing's syndrome (CD).
      Patients with the ectopic ACTH syndrome were significantly older (mean, 51.9 vs.
      40.2), were more likely to be male (58.8% vs. 27.4%), had shorter duration of
      clinical findings (mean, 11.6 vs. 39.9 months), were more likely to have
      hypokalemia (50% vs. 8.6%), had higher baseline 24-h urinary free cortisol [mean,
      8317 vs. 1164 nmol/day (3015 vs. 422 microg)] and plasma ACTH levels [mean, 47
      vs. 17 pmol/L (210 vs. 78 pg/mL)] and were less likely to suppress urinary free
      cortisol or plasma cortisol with high dose dexamethasone using the standard
      criterion of 50% or more suppression compared with patients with pituitary
      dependent Cushing's syndrome. Based upon the standard criterion, the sensitivity
      and specificity of the high dose dexamethasone suppression test for the diagnosis
      of pituitary-dependent Cushing's syndrome were 81.0% and 66.7%, respectively.
      Although the mean percent suppression was significantly greater for patients with
      CD than for those with the ectopic ACTH syndrome (72.2% vs. 41.3%), the range of
      suppression was 0-99% for each diagnosis. The area under the receiver operating
      characteristic curve was 0.710 (95% confidence interval, 0.541-0.879). Logistic
      regression models were used to evaluate the probability of CD given the
      responsiveness to high dose dexamethasone suppression testing before and after
      adjustment for the potential contributions of other factors. A model including
      all of the variables (age, sex, duration, presence of hypokalemia, urinary free
      cortisol, and plasma ACTH) had a diagnostic accuracy of 92.7%. A model including
      all of these variables plus a binary variable indicating whether the patient met
      the criterion of suppression by 50% or more resulted in 95.6% accuracy, whereas
      substitution of this binary variable by percent suppression resulted in a model
      with 94.1% accuracy. There were no statistically significant differences among
      these models; their values for the c statistic, which is equivalent to the area
      under the curve in a receiver operating characteristic analysis, were all greater
      than 0.9. Logistic regression models indicate that the results of the
      dexamethasone suppression test add little to the differential diagnosis of ACTH
      dependent Cushing's syndrome, especially after taking other clinical information
      into account. In our patient population, the sensitivity and specificity of the
      dexamethasone suppression test were less than those reported by others. However,
      because 20-33% of cases of ectopic ACTH syndrome are misdiagnosed with these
      logistic regression models, other techniques are necessary to achieve greater
      diagnostic accuracy.

PMID- 9177383
TI  - Studies of the impact of a liver glucokinase promoter variant on glucose
      tolerance and insulin sensitivity index.
AB  - Because a frequently occurring nucleotide substitution at position -258 in the
      liver glucokinase promoter has been reported to be associated with impaired
      promoter activity, we have examined in Danish Caucasians whether this variant is
      associated with alterations in glucose tolerance and/or the insulin sensitivity
      index (Si). Among 246 Danish Caucasian patients with noninsulin-dependent
      diabetes mellitus, the allelic frequency of the -258 promoter variant was 15.2%
      (95% confidence interval: 12.0-18.4%) vs. 16.5% (13.2-19.8%) among 242 matched
      control subjects. In the control group, the glucokinase variant was not related
      to serum insulin or plasma glucose levels before or during an oral glucose
      tolerance test. Neither was the gene variant among 380 young, healthy subjects
      associated with altered Si or altered insulin secretion after an i.v. glucose
      load. We conclude that in Danish Caucasians, the -258 glucokinase promoter
      variant has no impact on glucose tolerance, whole-body Si, or insulin secretion.

PMID- 9177384
TI  - Increased 12-lipoxygenase expression in breast cancer tissues and cells.
      Regulation by epidermal growth factor.
AB  - The interaction of growth factors, such as epidermal growth factor (EGF) with
      their receptors, on breast cancer cells can lead to the hydrolysis of
      phospholipids and release of fatty acids, such as arachidonic acid, which can be
      further metabolized by the lipoxygenase (LO) pathway. Several LO products have
      been shown to stimulate oncogenes and have mitogenic and chemotactic effects. In
      this study, we have evaluated the regulation of 12-LO activity and expression in
      breast cancer cells and tissues. Leukocyte-type 12-LO messenger RNA (mRNA)
      expression was studied by a specific RT-PCR method in matched, normal, uninvolved
      and cancer-involved breast tissue RNA samples from six patients. In each of these
      six patients, the cancer-involved section showed a much higher level of 12-LO
      mRNA than the corresponding normal section. 12-LO mRNA levels also were greater
      in two breast cancer cell lines, MCF-7 and COH-BR1, compared with the
      nontumorigenic breast epithelial cell line, MCF-10F. The growth of the MCF-7
      cells was significantly inhibited by two specific LO blockers but not by a
      cyclooxygenase blocker. Treatment of serum-starved MCF-7 cells with EGF for 4 h
      led to a dose-dependent increase in the formation of the 12-LO product, 12
      hydroxyeicosatetraenoic acid. EGF treatment also increased the levels of the
      leukocyte-type 12-LO protein expression at 24 h. These results suggest that
      activation of the 12-LO pathway may play a key role in basal and EGF-induced
      breast cancer cell growth.

PMID- 9177385
TI  - Steroidogenic factor 1 messenger ribonucleic acid expression in steroidogenic and
      nonsteroidogenic human tissues: Northern blot and in situ hybridization studies.
AB  - Steroidogenic factor-1 (SF-1), a tissue-specific orphan nuclear receptor,
      regulates the genes of several steroidogenic enzymes, Mullerian inhibiting
      substance, and the gonadotrophins. Also, this transcription factor is crucial for
      hypothalamic, adrenal, and gonadal organogenesis in the mouse. We recently cloned
      the human SF-1 (hSF-1) complementary DNA (cDNA) and now report the distribution
      of this factor's messenger RNA (mRNA) in human tissues. Northern blot analyses of
      peripheral tissues revealed high hSF-1 mRNA expression in the adrenal cortex and
      the gonads, but no hSF-1 mRNA was detected in the placenta. High hSF-1 mRNA
      expression also was seen in the spleen. In this tissue, in addition to the main
      transcript of 3.5-4 kb seen in the adrenal and gonads, two additional transcripts
      of 4.4 kb and 8 kb were noted. The additional 4.4-kb transcript also was seen in
      several peripheral tissues and various components of the brain. However, adult
      liver and heart showed only the 4.4-kb transcript. In the human brain, hSF-1 mRNA
      expression was widespread, including several components of the limbic system. In
      situ hybridization studies confirmed the strong expression of hSF-1 mRNA in
      adrenal cortex, ovary, testis, and the spleen, primarily within
      reticuloendothelial cells. Thus, in the human, the hSF1 mRNA is present in both
      steroidogenic and nonsteroidogenic tissues, albeit not in the placenta. In the
      central nervous system, the expression of hSF-1 mRNA is widespread. It is
      composed of several different mRNA species distributed in a tissue-specific
      fashion. These findings suggest that hSF-1 may play a role in
      reticuloendothelial/immune cell maturation and/or function, as well as nervous
      system development and/or neurosteroid biosynthesis.

PMID- 9177386
TI  - Leptin concentrations, sex hormones, and cortisol in nondiabetic men.
AB  - Leptin, the product of the human ob gene, is increased in obese individuals,
      suggesting resistance to its effect. However, there is a variability in leptin
      levels at each level of body mass index, suggesting that genetic and
      environmental factors other than overall adiposity may regulate leptin
      concentrations. No data currently exist on the relation of sex hormones to leptin
      concentrations in men. We examined the relation ofleptin levels to sex hormone
      binding globulin, total and free testosterone, dehydroepiandrosterone sulfate,
      estradiol, and cortisol in 87 normoglycemic men. Leptin levels were significantly
      correlated with free testosterone (r = -0.14; P < 0.05), sex hormone-binding
      globulin (r = -0.26; P < 0.05), total testosterone (r = -0.32; P < 0.01), and
      cortisol (r = -0.09; P = NS). However, after adjustment for body mass index (or,
      alternatively, waist or hip circumference), leptin concentrations were not
      significantly related to sex hormones or cortisol. Our data suggest that in men,
      sex hormones are not important independent modifiers of leptin concentrations.

PMID- 9177387
TI  - Spontaneous pubertal development in Turner's syndrome. Italian Study Group for
      Turner's Syndrome.
AB  - The incidence of spontaneous puberty in Turner's syndrome is reported to be
      between 5-10% and, more recently in some series, as high as 20%. In an Italian
      retrospective multicenter study, of 522 patients older than 12 yr with Turner's
      syndrome, 84 patients (16, 1%) presented spontaneous pubertal development with
      menarche that occurred at a chronological age of 13.2 +/- 1.5 yr (mean +/- SD)
      and a bone age of 12.9 +/- 1.9 yr. Karyotype distribution in the whole group was
      as follows: 52.1% (272 patients) X-monosomy (45,X), 13.2% (69 patients) mosaicism
      characterized by X-monosomy and cellular line with no structural abnormalities of
      the second X, 19.9% (104 patients) mosaicism characterized by X-monosomy and
      cellular line with structural abnormalities of the second X, and 14.8% (77
      patients) structural abnormalities of the second X. Menstrual cycles were still
      regular in 30 patients at 9.2 +/- 5.0 yr after menarche, 12 developed secondary
      amenorrhea 1.6 +/- 2.0 yr after menarche, and 19 had irregular menstrual cycles
      0.9 +/- 1.8 yr after menarche. As signs of spontaneous puberty developed in 14.0%
      of X-monosomic patients and in 32.0% of patients with cell lines with more than
      one X, the presence of the second X seems to have a cardinal influence on the
      appearance of spontaneous puberty. Spontaneous pregnancy occurred in 3 patients
      (3.6%). The presence of chromosomal abnormalities and malformations in 2 of 3
      pregnancies led us to agree with other investigators in discouraging unassisted
      pregnancies. Treatment with GH does not seem to exert any influence on either the
      age of onset or the prevalence of spontaneous pubertal development in Turner's
      syndrome. The increased percentage of spontaneous menarche is Turner's syndrome
      reported in the recent literature might be due to increased ascertainment by
      diligent screening for Turner's syndrome in girls with short stature and mild or
      no Turner's syndrome stigmata, even though they may be menstruating.

PMID- 9177388
TI  - Absence of growth hormone effects on cognitive function in girls with Turner
      syndrome.
AB  - Turner syndrome (TS) is a genetic disorder characterized by short stature,
      gonadal dysgenesis, and a particular neurocognitive profile of normally developed
      language abilities (particularly verbal IQ) and impaired visual-spatial and/or
      visual-perceptual abilities. We have followed a large sample of girls with Turner
      syndrome who were enrolled in a long-term, double-blind, placebo-controlled trial
      of the effects of growth hormone (GH) treatment on final adult height. This study
      provides a unique opportunity to prospectively evaluate the effects of GH
      treatment on neurocognitive function in this population of girls with Turner
      syndrome. The GH- and placebo-treated Turner syndrome subjects were well matched
      for age, treatment duration, race, karyotype, and socioeconomic status. Treatment
      (GH or placebo) durations ranged from 1-7 yr. Whether GH deficiency and/or
      treatment in childhood and adolescence influences cognitive outcome in short
      children or GH-children is controversial. The major result of this study was the
      absence of GH treatment effects on cognitive function in girls with Turner
      syndrome. Our findings are in agreement with most of the previous studies that
      found no apparent growth hormone treatment effects on cognitive function in
      growth-hormone deficient children. We conclude that this study does not support a
      role for growth hormone in influencing childhood brain development in girls with
      Turner syndrome. Their characteristic nonverbal neurocognitive deficits were not
      altered with GH treatment into early adolescence.

PMID- 9177389
TI  - The effect of growth hormone (GH) on histomorphometric indices of bone structure
      and bone turnover in GH-deficient men.
AB  - We investigated the effects of GH on bone structure and turnover by
      histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were
      obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28
      +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had
      multiple pituitary hormone deficiencies. Patients were randomly assigned to four
      treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69,
      and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received
      placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the
      subsequent 6 months. GH treatment resulted in an increase of cortical thickness
      from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume
      did not change. Bone formation variables increased significantly: osteoid surface
      increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface
      increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate
      increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded
      surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25
      +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased
      significantly (P = 0.001), whereas the resorption period, including reversal
      phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased
      from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a
      stimulated bone turnover as a result of GH treatment and a shorter resorption and
      reversal time. The increased turnover did not result in an increased trabecular
      bone volume, but the cortical thickness increased significantly.

PMID- 9177390
TI  - Urinary excretion of aquaporin-2 in the diagnosis of central diabetes insipidus.
AB  - We determined whether alteration in urinary excretion of aquaporin-2 (UAQP-2) is
      of value to diagnose central diabetes insipidus (CDI). First, UAQP-2 was
      determined in 16 normal subjects under ad libitum water drinking (n = 6) and
      after an overnight dehydration (n = 10). UAQP-2 has a positive correlation with
      plasma arginine vasopressin (AVP) levels (r = 0.61, P < 0.05) but not with
      urinary osmolality (Uosm). Second, a hypertonic saline (5% NaCl)-infusion test
      was studied in 5 normal subjects (21 to 25 yr old) and 10 patients with CDI (22
      68 yr). After drinking water ad libitum, they were given 20 mL/kg water orally
      and then given 5% NaCl (0.05 mL/kg x min) i.v. for 120 min. Finally, 0.1 U of AVP
      was administered i.v. During the period, 30-min urine collections were made. In
      the normal subjects, after the infusion of 5% NaCl, plasma AVP levels and Uosm
      markedly increased in parallel with an increase in plasma osmolality (Posm, 294
      320 mOsm/kg H2O; Uosm, 102-737 mOsm/kg H2O; AVP, 0.4-2.6 pg/mL, P < 0.001). In
      the CDI patients, plasma AVP and Uosm failed to increase, despite an increase in
      Posm (Posm, 306-332; Uosm, 102-164; AVP, 0.9-1.2). UAQP-2 was markedly greater in
      the normal subjects than the CDI patients (7.2 vs. 0.9 pmol/L/mg creatinine, P <
      0.05) under water intake ad libitum. UAQP-2 was changeable in the wide range in
      physiological condition. After the 5%-NaCl infusion, UAQP-2 elevated to 12.5 from
      0.9 pmol/L x mg creatinine in the normal subjects. In contrast, UAQP-2 remained
      low during the 5%-NaCl infusion in the CDI patients. Exogenous AVP promptly
      increased UAQP-2 to a similar extent in two groups of the normal subjects and the
      CDI patients. These results indicate that measurement of UAQP-2 is of value to
      diagnose CDI in the 5%-NaCl infusion test.

PMID- 9177391
TI  - Effects of hepatic glycogen content on hepatic insulin action in humans:
      alteration in the relative contributions of glycogenolysis and gluconeogenesis to
      endogenous glucose production.
AB  - Hepatic glycogen content varies by almost 2-fold during the day, generally
      increasing from a nadir before breakfast to a peak 4-5 h after supper. To
      determine whether differences in hepatic glycogen content of this magnitude alter
      hepatic insulin action, nine subjects were studied on two occasions. On one
      occasion saline was infused, whereas on the other occasion an infusion of glucose
      [16.4 micromol/kg lean body mass (-lbm) x min] was started immediately after
      supper and continued throughout the night so as to spare hepatic glycogen. The
      nocturnal glucose infusion resulted in higher (P < 0.05) plasma glucose (6.0 +/-
      0.1 vs. 5.1 +/- 0.1 mmol/L) and insulin (127 +/- 38 vs. 49 +/- 9 pmol/L)
      concentrations, and lower (P < 0.05) plasma glucagon concentrations (74 +/- 11
      vs. 97 +/- 20 pg/mL) than did saline infusion. As anticipated, endogenous glucose
      production (EGP) was substantially lower (P < 0.001) during the glucose than
      during the saline infusion (7.0 +/- 0.9 vs. 19.4 +/- 1.3 micromol/kg-lbm x min).
      After discontinuation of the glucose infusion, glucose and insulin concentrations
      fell to levels that no longer differed from those observed during the saline
      infusion. In contrast, EGP increased to rates that were higher (P < 0.05) than
      those observed over the same interval after overnight saline infusion (19.2 +/-
      1.2 vs. 16.5 +/- 0.7 micromol/kg-lbm x min). Despite higher EGP, the rate of
      incorporation of 14CO2 into glucose was lower (P < 0.001) after glucose than that
      after saline infusion (9.8 +/- 1.2% vs. 24.4 +/- 3.0%), implying a reciprocal
      relationship between hepatic glycogen content and gluconeogenesis. On the other
      hand, when differences in basal rates were taken into account, insulin-induced
      suppression of both EGP and incorporation of 14CO2 into glucose did not differ on
      the two occasions. Thus, whereas hepatic glycogen content influences both the
      absolute rate of EGP and the percent contribution of gluconeogenesis to EGP, it
      does not alter hepatic insulin action.

PMID- 9177392
TI  - Alterations in the glucose-stimulated insulin secretory dose-response curve and
      in insulin clearance in nondiabetic insulin-resistant individuals.
AB  - Plasma glucose and insulin responses to a graded i.v. infusion of glucose were
      compared in two groups of glucose-tolerant women divided on the basis of their
      insulin sensitivity. Resistance to insulin-mediated glucose disposal was measured
      using the insulin suppression test, and the women studied were chosen to
      represent the highest and lowest quartiles of insulin resistance seen in the
      normal population. The sensitivity of the pancreatic beta-cell to glucose was
      assessed by measuring the glucose, insulin, and C peptide concentrations in
      response to continuous graded i.v. infusions of glucose at rates of 1, 2, 3, 4,
      6, and 8 mg/kg x min for 40 min each. In addition, insulin secretion rates in
      response to the graded glucose infusion, calculated over each sampling period,
      were derived from deconvolution of peripheral plasma C peptide concentrations,
      using a two-compartment model of C peptide kinetics and standard parameters for C
      peptide clearance. Although plasma glucose concentrations were only slightly
      higher throughout the glucose infusion, the insulin concentrations were
      approximately doubled in the insulin-resistant subjects. When expressed as a
      function of the molar increments in plasma glucose achieved during the glucose
      infusion studies, the insulin-resistant women had a 90% higher (684 +/- 55 vs.
      360 +/- 36 pmol/L x mmol/L; P < 0.001) total integrated plasma insulin response
      as the glucose concentration was increased from 5 to 9 mmol/L. However, the total
      integrated insulin secretory rate was only increased by 37% (1494 +/- 133 vs.
      1093 +/- 125 pmol/mmol/L x min; P < 0.05) in the insulin-resistant group. This
      discrepancy suggested that insulin clearance was lower in the insulin-resistant
      subjects, and the calculation of this value, as the ratio of the total secretion
      of insulin to the area under the plasma insulin curve, was significantly lower in
      the insulin-resistant group (1.25 +/- 0.05 vs. 1.87 +/- 0.16 L/min x m2; P <
      0.005). These results show that the hyperinsulinemia of insulin resistance
      results from an increase in insulin secretion secondary to a shift to the left of
      the glucose-stimulated insulin response curve as well as a decrease in insulin
      clearance.

PMID- 9177393
TI  - The protein kinase A pathway inhibits c-jun and c-fos protooncogene expression
      induced by the protein kinase C and tyrosine kinase pathways in cultured human
      thyroid follicles.
AB  - We have previously demonstrated antagonistic interactions between the major
      signal transduction pathways in human thyroid follicles: TSH acting via protein
      kinase A (PKA) attenuated phorbol ester [acting via protein kinase C (PKC)] as
      well as epidermal growth factor (EGF)-protein tyrosine kinase (PTK)-mediated cell
      proliferation, whereas the PKC and PTK pathways inhibited PKA-mediated cell
      differentiation. In view of the key role played by the protooncogenes c-jun and c
      fos in the cascade of events leading to cell proliferation and differentiation,
      we examined whether the antagonism we observed between the pathways could be
      related to changes in the expression of these genes. The experimental model used
      was the same in vitro system as that used in the above study on cell growth and
      differentiation: thyroid follicles of human origin cultured in suspension under
      serum-free conditions. Both EGF (1-50 ng/mL) and the phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (TPA; 10(-11)-10(-7) mol/L) dose and time
      dependently stimulated c-jun and c-fos messenger ribonucleic acid (mRNA)
      expression. The c-jun and c-fos mRNA stimulation elicited by TPA was reduced by
      the PKC inhibitors, chelerythrine and staurosporine, and could not be mimicked by
      4alpha-phorbol 12,13-didecanoate (a phorbol ester that fails to activate PKC),
      whereas the stimulation induced by EGF was diminished by the PTK inhibitor,
      genistein. This indicates a PKC- and PTK-mediated pathway triggered by TPA and
      EGF, respectively. TSH induced an increase in c-jun and c-fos mRNA, which, though
      significant, was small compared to that elicited by TPA or EGF. Addition of TSH
      (0.1-0.5 mU/mL), however, to either TPA or EGF dose dependently inhibited the c
      jun and c-fos mRNA elicited by these agents. The repressive action of TSH on the
      effects of TPA and EGF mRNA were mimicked by forskolin and 8-bromo-cAMP,
      suggesting that the TSH inhibitory action is PKA mediated. The TSH inhibitory
      action seems to require de novo protein synthesis, as it was abrogated in the
      presence of cycloheximide. In conclusion, the present study provides novel data
      on c-jun and c-fos gene expression and their modulation by the major signal
      transduction pathways operating in human thyrocytes. Moreover, using the same
      serum-free system of human thyroid follicles cultured with the same agents and at
      the same doses as in our previous study on cell growth and differentiation, we
      found the TSH/PKA pathway to inhibit PKC- and EGF/tyrosine kinase-induced c-jun
      and c-fos mRNA, i.e. antagonistic effects parallel to those previously observed
      measuring cell proliferation. The findings suggest an association between human
      thyroid cell proliferation and c-jun and c-fos gene expression.

PMID- 9177394
TI  - Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional
      status and potential role in resistance to weight gain.
AB  - Studies in rodents have shown that leptin acts in the central nervous system to
      modulate food intake and energy metabolism. To evaluate the possible role of
      leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal
      fluid (CSF) and plasma leptin concentrations in anorexic patients and controls.
      Subjects included 11 female patients with anorexia nervosa studied at low weight
      and after treatment, and 15 healthy female controls. Concentrations of leptin in
      blood and CSF were measured by RIA. Patients with anorexia nervosa, compared to
      controls, had decreased concentrations of leptin in CSF (98 +/- 26 vs. 160 +/- 58
      pg/mL; P < 0.0005) and plasma (1.75 +/- 0.46 vs. 7.01 +/- 3.92 ng/mL; P < 0.005).
      The CSF to plasma leptin ratio, however, was higher for patients (0.060 +/-
      0.023) than for controls (0.025 +/- 0.007; P < 0.0001). At posttreatment testing,
      although patients had not yet reached normal body weight, CSF and plasma leptin
      concentrations had increased to normal levels. These results demonstrate the
      dynamic changes in plasma and CSF leptin during positive energy balance in
      anorexia nervosa. The results further suggest that normalization of CSF leptin
      levels before full weight restoration during treatment of anorexic patients could
      contribute to resistance to weight gain and/or incomplete weight recovery.

PMID- 9177395
TI  - Ex vivo expansion of human pancreatic endocrine cells.
AB  - Cell transplantation as a therapy for type 1 diabetes is facilitated by ex vivo
      cell expansion of pancreatic beta-cells without loss of differentiative
      characteristics. The aim of this study was to determine the optimal conditions
      for in vitro growth of functional human pancreatic endocrine tissue. We examined
      the mitogenicity of matrixes from a variety of cell lines; proliferation was
      greater in cells growing on matrixes from bladder carcinoma cell lines,
      especially in monolayers grown on matrix from the human cell line HTB-9. After 14
      day culture, there was a more than 100-fold proliferative increase, which was
      augmented to a more than 200-fold when hepatocyte growth factor/scatter factor
      was added; however, hepatocyte growth factor/scatter factor induced a rapid
      decrease in insulin content. Without the growth factor, fetal cell monolayers
      expanded 4-fold with no insulin loss; however, after 12-fold expansion, the
      insulin levels decreased to 40% of those in unexpanded cells. Adult islet cells
      expanded 3-fold without insulin loss. After 5-fold expansion, insulin levels
      decreased by 25% compared to those in free floating islets while retaining a
      normal response to secretagogues. Together, these results indicate that HTB-9
      matrix provides the best stimulatory effect on replication of human endocrine
      cells, with little loss of in vitro function.

PMID- 9177396
TI  - Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma
      cell lines.
AB  - Somatostatin (SRIH) analogs can suppress the proliferation of human
      differentiated thyroid carcinoma cell lines that express SRIH receptors (SSTRs)
      demonstrated by radioligand binding analysis. Five distinct human SSTR subtypes
      (hSSTR1-5) that bind native SRIH exhibit diverse affinities to a wide range of
      SRIH analogs. Reverse transcriptase-PCR amplification of ribonucleic acids (RNAs)
      obtained from normal thyroid tissues and nine human thyroid carcinoma cell lines,
      grown as monolayer cultures and xenograft tumors in nude mice, were used to
      discriminate expression of SSTR subtype messenger RNAs (mRNAs). The cell lines
      were derived from a follicular adenoma (KAK-1), two follicular carcinomas (MRO-87
      and WRO-82), two papillary carcinomas (NPA87 and KAT-10), and four anaplastic
      thyroid carcinomas (DRO-90, ARO-81, KAT-4, and KAT-18). Most thyroid cancer cell
      line monolayers and xenografts expressed SSTR3 and SSTR5 mRNAs. SSTR1 expression
      was more varied between monolayers and xenografts, whereas SSTR2 mRNA was only
      faintly detectable at the most extreme resolution. SSTR4 mRNA was faintly
      positive in only one anaplastic carcinoma xenograft. Normal thyroid also
      expressed SSTR3 and SSTR5 mRNAs, with only faint expression of SSTR1 and SSTR2
      mRNAs (in one of five and three of five samples, respectively). SSTR mRNA
      expression was dependent upon in vitro culture conditions, as xenograft SSTR mRNA
      expression tended to decrease compared to that in each respective monolayer
      culture. Characterization of SSTR subtype expression in human thyroid carcinomas
      may permit targeting of specific SRIH analogs to inhibit proliferation of
      differentiated and anaplastic thyroid carcinomas in patients.

PMID- 9177397
TI  - Proteolysis of insulin-like growth factor-binding protein-3 by human skin
      keratinocytes in culture in comparison to that in skin interstitial fluid: the
      role and regulation of components of the plasmin system.
AB  - Proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) is an
      important determinant of IGF action on cells. We have investigated this in a
      human skin keratinocyte cell line HaCaT. Although these cells did not normally
      produce an active IGFBP-3 protease, addition of plasminogen resulted in a dose
      dependent proteolysis of endogenous and exogenous IGFBP-3, producing fragments
      similar to those cleaved by skin interstitial fluid, but different from those
      generated by plasmin. Protease inhibitor profiles suggested the enzyme in the
      conditioned medium to be a calcium-dependent serine protease. Exogenous IGFBP-3
      either inhibited or slightly stimulated IGF-I-induced cell proliferation when it
      was coincubated or preincubated with the cells, respectively. Both effects were
      attenuated in the presence of plasminogen. Preincubation of cells with IGF-I or
      long R3 IGF-I divergently changed plasminogen activator inhibitor-1 and -2
      secretion, but only IGF-I blocked IGFBP-3 proteolysis. Such inhibition was also
      observed in a cell-free protease assay. IGF-I, however, had no effect on plasmin
      induced IGFBP-3 degradation. Together, these data indicate that an IGFBP-3
      protease similar to that in skin interstitial fluid is generated in plasminogen
      treated HaCaT cells, and it attenuates the effects of IGFBP-3 on IGF action. IGF
      I, probably by coupling with IGFBP-3, can protect it from the action of this
      protease.

PMID- 9177398
TI  - Triiodothyronine and follicle-stimulating hormone, alone and additively together,
      stimulate production of the tissue inhibitor of metalloproteinases-1 in cultured
      human luteinized granulosa cells.
AB  - Thyroid disorders have been frequently associated with menstrual disturbances and
      impaired fertility. To characterize the nature of thyroid hormone action in the
      ovary, the direct effects of T3-gonadotropin interactions were investigated in
      vitro using a culture system of human luteinized granulosa cells in serum-free
      medium. Although FSH alone was devoid of any significant effect on cell
      proliferation, it inhibited T3-stimulated cell growth. The electrophoretic
      profiles of the radiolabeled proteins induced by the different hormonal
      treatments revealed similarity in overall protein patterns but differences in
      intensity of labeling. Human CG, alone or combined with T3, had no major
      influence on the total intensity of labeling compared with control, whereas T3 or
      FSH alone reduced total labeling intensity but a 30,000 Da protein band was
      increased. FSH combined with T3 augmented the total intensity of labeling,
      including the 30,000-Da protein band. Western blot analysis revealed the presence
      of the tissue inhibitor of metalloproteinases-1 (TIMP-1), mol wt 30,000, known to
      play a key role in ovarian function. TIMP-1 was dose dependently stimulated by T3
      and FSH, and an additive effect was obtained when both hormones were combined.
      This is the first report of TIMP-1 modulation by FSH in ovarian cells and of an
      effect by thyroid hormone on TIMP-1 levels. The study shows TIMP-1 induction in
      human ovarian cells not only by FSH, i.e. via a probable protein kinase A
      mechanism, but also demonstrates an additional mode of TIMP-1 hormonal induction:
      via thyroid hormone stimulation, acting by modulation of gene transcription. The
      present study provides novel data on TIMP-1 hormonal modulation and of direct T3
      in vitro ovarian effects that may account for the in vivo indications of a
      thyroid-ovarian connection.

PMID- 9177399
TI  - Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and
      cortisol before and after weight loss.
AB  - Little is known about the effects of intentional weight loss on the function of
      the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied
      the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2)
      before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss
      program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula
      diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020
      6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before
      caloric restriction and during the last 3 weeks of caloric stabilization with a 3
      h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and
      cortisol values were compared to those of a control group of 12 normal weight
      women. Before caloric restriction, both ACTH and cortisol responses to oCRH were
      similar in obese women and normal weight controls. Weight loss did not
      significantly alter the ACTH response to oCRH; however, the total plasma cortisol
      response to oCRH decreased significantly with weight loss (area under the curve,
      96,320 +/- 21,040 nmol/L x min before weight loss; 82,450 +/- 22,460 nmol/L x min
      after weight loss; P < 0.001). Cortisol-binding globulin also decreased
      significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to
      values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to
      those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for
      plasma free cortisol, either before or 180 min after oCRH treatment, showed no
      significant changes in cortisol responses resulting from weight loss. As plasma
      free cortisol was not altered by weight reduction, the decrease in the total
      cortisol response to oCRH after weight loss appears to be secondary to
      significant decreases in cortisol-binding globulin. We conclude that when obese
      women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such
      weight reduction does not significantly affect the HPA axis.

PMID- 9177400
TI  - Growth hormone-binding protein in normal and pathologic gestation: correlations
      with maternal diabetes and fetal growth.
AB  - To date, measurements of GH-binding protein (GHBP) during human pregnancy have
      been carried out using assays susceptible to interference by the elevated levels
      of human placental GH typical of late gestation. We recruited a large cohort of
      pregnant women (n = 140) for serial measurements of GHBP and used the ligand
      immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout
      gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90
      nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and
      0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester
      correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP
      levels in pregnancies complicated by noninsulin-dependent diabetes mellitus
      (NIDDM) were substantially elevated at all gestational ages. The mean value in
      the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01).
      In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed
      reduced GHBP concentrations at 36-38 weeks. The correlation between body mass
      index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as
      is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks
      gestation, GHBP was significantly elevated (P < 0.01) in those women whose
      neonates had low birth weight (< 10th percentile). In early gestation (< 14
      weeks), GHBP tended to be higher in women whose fetuses were designated to be at
      risk of intrauterine growth retardation (1.39 nmol/L; n = 4; compared with 1.07
      nmol/L in normals), but this did not reach statistical significance. Although
      both NIDDM and IDDM pregnancies are at risk of fetal macrosomia, their GHBP
      concentrations are markedly divergent. This paradox and the roles of glucose and
      insulin in the regulation of GHBP during gestation warrant further investigation.

PMID- 9177401
TI  - Flow cytometric analyses of antibody binding to Chinese hamster ovary cells
      expressing human thyrotropin receptor.
AB  - To develop a method that can be used to directly detect binding of antibodies to
      TSH receptor (TSHr), we employed Chinese hamster ovary (CHO) cells permanently
      transfected with a human TSHr complementary DNA (CHOR). These cells showed
      increased cAMP production when treated with either human TSH or thyroid
      stimulating antibodies and decreased TSH-mediated cAMP production when treated
      with stimulation-blocking antibodies. We employed flow cytometry and rabbit
      antibodies against the extracellular domain of the TSHr (ETSHr) to test whether
      these cells can be used to directly detect and quantitate the binding of anti
      TSHr antibodies. Rabbit anti-ETSHr bound specifically to CHOR cells, and the
      binding could be blocked with purified ETSHr. To test the feasibility of using
      these cells for epitope mapping, we tested the binding of rabbit antibodies
      raised against several synthetic TSHr peptides. Rabbit antipeptide 92 (amino
      acids 12-30) and 91 (amino acids 32-46) showed little or no binding to the CHOR
      cells. In contrast, antibodies raised against peptides 93 (amino acids 316-330),
      95 (aa 325-345), 3A (aa 357-372), 367 (aa 367-386), and 1B (aa 362-376) showed
      significant binding to the CHOR cells. The specificity of binding of antipeptide
      antibodies was demonstrated by a complete inhibition of binding by corresponding
      peptides. When TSH-binding inhibitory Ig-positive sera from 15 patients with
      hyperthyroidism were tested, 8 of them showed specific binding to the CHOR cells
      compared to their relative binding to normal CHO cells; sera from all normal
      individuals tested did not exhibit specific binding to CHOR cells. These studies
      showed the usefulness of CHOR cells and flow cytometry in epitope mapping using
      sera with known specificities and the potential usefulness of the technique to
      detect anti-TSHr antibodies in patient sera.

PMID- 9177402
TI  - Gestational age-dependent expression of insulin-like growth factor-binding
      protein-1 (IGFBP-1) phosphoisoforms in human extraembryonic cavities, maternal
      serum, and decidua suggests decidua as the primary source of IGFBP-1 in these
      fluids during early pregnancy.
AB  - The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are
      important regulators of fetal and maternal tissue development during pregnancy.
      Posttranslational modification of IGFBP-1 yields up to six IGFBP-1
      phosphovariants and a nonphosphorylated form, which in vitro, have some different
      properties. Nonphospho IGFBP-1 has less affinity for IGFs than the phospho
      isoforms and also may have IGF-independent actions. Herein, we have investigated
      the complement of IGFBP-1 phosphoisoforms present in extraembryonic coelomic
      (EEC) fluid, amniotic fluid (AF), and maternal serum (MS) throughout human
      gestation. Also, to determine potential tissue source(s) of IGFBP-1 in these
      fluids, we have quantified IGFBP-1 and examined IGFBP-1 phosphoisoforms in
      conditioned media (CM) from maternal decidua, fetal liver, and fetal kidney
      explants throughout gestation. Western immunodetection revealed that IGFBP-1,
      present in EEC and AF in early pregnancy and in CM from early pregnancy decidua,
      is primarily in the nonphosphorylated form. MS in this period contains primarily
      the nonphospho form and, as in nonpregnant adults, the highly phosphorylated form
      of IGFBP-1. The phosphorylation profile of IGFBP-1 in AF, MS, and decidua CM
      changes as pregnancy progresses. All the IGFBP-1 phosphoisoforms ultimately are
      produced by decidua and are present in midgestation MS, and all but the most
      highly phosphorylated form are present in AF. In late gestation, MS contains
      primarily the highly phosphorylated form. In contrast, profiles in CM from
      explants of fetal liver and kidney at different gestational ages remain
      unchanged. Nonphosphorylated IGFBP-1 is the primary form in fetal kidney CM,
      whereas fetal liver CM contains all IGFBP-1 phosphoisoforms. Concentrations of
      IGFBP-1 in fetal liver and kidney CM are significantly lower (482 +/- 146 and 120
      +/- 32 ng/mL x 100 mg wet wt tissue, respectively) than in decidua CM (11,417 +/-
      2,358 ng/mL x 100 mg wet wt tissue). The data cumulatively suggest that maternal
      decidua is the primary source of IGFBP-1 in EEC, AF, and MS in early pregnancy
      and that fetal liver and kidney are not likely significant contributors. The
      presence of nonphospho IGFBP-1 in AF, EEC, and MS suggests an important role for
      this isoform during early gestation.

PMID- 9177403
TI  - Amino acid neurotransmission and initiation of puberty: evidence from nonketotic
      hyperglycinemia in a female infant and gonadotropin-releasing hormone secretion
      by rat hypothalamic explants.
AB  - The pulse frequency of hypothalamic GnRH secretion increases at the onset of
      puberty. In rodents and primates, this process involves facilitatory and
      inhibitory effects mediated through hypothalamic N-methyl-D-aspartic acid (NMDA)
      and gamma-aminobutyric acid (GABA) receptors, respectively. Precocious puberty
      was observed in an 11-month-old girl with nonketotic hyperglycinemia. This was
      thought to result from the effect of high concentrations of glycine (112
      micromol/L in cerebrospinal fluid; normal, 3-12) acting on NMDA receptors as a
      coagonist of glutamate. Regression of pubertal development during anticonvulsive
      treatment with GABA agonists (loreclezole and vigabatrin) suggested that the
      stimulatory effects of glycine could be overcome by GABA receptor-mediated
      inhibition. These two hypotheses were tested in the in vitro model of the
      explanted hypothalamus from infantile (15-day-old) male rats. Glycine
      concentrations of 1-10 micromol/L increased the pulse frequency of GnRH
      secretion. This acceleration was prevented by 7-chlorokynurenic acid, a glycine
      antagonist at the NMDA receptor complex, and by the GABA agonist loreclezole. In
      addition, loreclezole and vigabatrin suppressed the developmental increase in the
      frequency of pulsatile GnRH secretion. The observation of precocious puberty in
      an infant with hyperglycinemia followed by pubertal regression during GABA
      agonist therapy and the in vitro findings in hypothalamic explants suggest that
      stimulatory inputs mediated through NMDA receptors and inhibitory inputs through
      GABA receptors are involved in the initiation of puberty.

PMID- 9177404
TI  - The predictive value of biochemical markers of bone turnover for bone mineral
      density in early postmenopausal women treated with hormone replacement or calcium
      supplementation.
AB  - To compare the relative sensitivity and specificity of bone turnover indexes for
      bone loss or gain in early postmenopausal women, we performed a multicenter trial
      in 236 menopausal women (mean age, 51 yr), who were randomized to hormone
      replacement therapy (HRT) or calcium supplementation (CS; 500 mg/day) for 1 yr.
      Two markers of bone formation, osteocalcin (OC) and bone alkaline phosphatase
      (BSAP), and two markers of bone resorption, urinary N-telopeptide (NTx) and
      urinary free deoxypyridinoline (fDpd), as well as spine and femoral neck bone
      mineral density (BMD) were measured at baseline and 3, 6, and 12 months after
      treatment. Women receiving HRT (n = 105) showed a significant increase in spine
      BMD (+2.5%; P < 0.0001) and hip BMD (+1.0%; P = 0.02) compared to women receiving
      CS, who showed a decline at both sites (-1.1%; P < 0.01). All four markers showed
      time-dependent decreases in women receiving HRT (P < 0.001) and no change in
      women receiving CS alone. When baseline indexes of turnover were stratified by
      quartile, there was a significantly greater increase in BMD among those with the
      highest NTx, OC, and BSAP levels compared to that in those with the lowest NTx,
      OC, and BSAP levels (P < 0.05). The highest quartile for percent change from
      baseline to 6 months in fDpd, BSAP, and NTx was also associated with the greatest
      change in spine BMD at 1 yr. Receiver operator characteristic curves for percent
      change from baseline to 6 months in an individual marker to 1 yr change in BMD
      during HRT revealed that the percent change in NTx provided the greatest
      discrimination between gain and loss of BMD. When subjects receiving HRT were
      compared by their positive or negative skeletal response at 1 yr and their
      baseline turnover marker, initial NTx values were significantly higher in those
      that gained bone than in those that lost bone (P = 0.0002). CS women in the
      highest quartile for NTx at baseline had significantly greater decreases in spine
      BMD than subjects with the lowest NTx values (P < 0.005), although this was not
      true for fDpd (P < 0.20). In conclusion, for early postmenopausal women there are
      differential responses of biochemical markers to HRT and CS. Baseline urinary NTx
      and serum OC were the most sensitive predictors of change in spine BMD after 1 yr
      of either HRT or CS. Similarly, the percent change in NTx and OC from baseline to
      6 months best predicted bone gain or loss. We conclude that markers of bone
      formation and resorption can be used clinically to predict future BMD in early
      postmenopausal women.

PMID- 9177405
TI  - Biochemical markers for puberty in the monkey testis: desmosterol and
      docosahexaenoic acid.
AB  - We previously reported that the sperm of rhesus monkeys and humans uniquely
      contain large amounts of desmosterol not found in other tissues and have a high
      concentration of the highly polyunsaturated n-3 fatty acid, docosahexaenoic acid
      (22:6 n-3). However, the lipid composition of the testis, from which sperm
      originate, is unknown. During puberty, the testis undergoes remarkable
      morphological changes as testosterone levels rise and sperm production begins. We
      hypothesized that testicular maturation might also involve dramatic changes in
      lipid composition. Accordingly, we characterized the sterol and fatty acid
      composition of the testis of rhesus monkeys throughout the lifespan, from birth
      to old age. Although the cholesterol content in the testis remained relatively
      unchanged throughout life, the desmosterol content first decreased from 59
      microg/g in infants to 6 microg/g in prepubertal monkeys, increased to 83
      microg/g during puberty, and reached a plateau of 248 microg/g in the young
      adult, where it remained into old age. The polyunsaturated fatty acid composition
      of the testis also changed markedly. Docosahexaenoic acid (22:6 n-3) increased
      from 5.1% of total fatty acids in infants and juveniles to 18.1% in postpubertal
      young adults. Although some n-6 fatty acids, arachidonic (20:4 n-6) and linoleic
      (18:2 n-6), decreased from 16.0% and 10.0% in prepubertal juveniles,
      respectively, to 7.1% and 3.3% in young adults; dihomogamma-linolenic acid (20:3
      n-6), the precursor of 1 series PGs, increased greatly from 1.8% to 10.3%.
      Similar changes occurred in both membrane and storage lipids (phospholipids and
      triglycerides), respectively. After puberty, the testicular fatty acid pattern
      remained stable into old age. Our data demonstrated that puberty is accompanied
      by substantial changes in the lipid composition of the primate testis. These
      changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids
      may have important roles in sexual maturation.

PMID- 9177406
TI  - Coexpression of stromelysin-3 and insulin-like growth factor II in tumors of
      ectodermal, mesodermal, and endodermal origin: indicator of a fetal cell
      phenotype.
AB  - Stromelysin-3 (ST-3) is thought to play an important role in invasion and tumor
      progression. We have analyzed ST-3 expression in fibroblasts with defined
      topographical relations to breast cancers. We demonstrate that these fibroblasts
      exhibit the same distinctive pattern of messenger ribonucleic acid (mRNA)
      expression that we have previously shown for insulin-like growth factor II (IGF
      II). Tumor-derived fibroblasts and skin fibroblasts produce abundant ST-3 mRNA.
      Fibroblasts from normal breast stroma distant from the malignant tumor in the
      same patient express considerably less ST-3 mRNA. When we analyzed ST-3 and IGF
      II gene expression in sarcomas, we found a similar pattern of coexpression.
      Immunohistochemical analysis of IGF-II and ST-3 protein expression in sarcomas
      and breast tumors confirmed the mRNA data. ST-3 mRNA expression was also seen in
      most colon cancer cell lines, again matching reports of IGF-II gene expression.
      As the two proteins are known to play an important role during fetal growth and
      development, their coexpression in fibroblasts from malignant tumors of
      ectodermal (breast cancer) and mesodermal (sarcoma) origin and in epithelial
      cells of endodermal origin (colon cancer) implies a more primitive cellular
      phenotype. The regained ability to express such developmentally regulated
      proteins might, therefore, be a more general marker indicating a fetal-type
      phenotype of cells in a malignant tumor.

PMID- 9177407
TI  - Insulin secretion and sensitivity in black versus white prepubertal healthy
      children.
AB  - We had previously demonstrated greater insulin secretion and lower insulin
      sensitivity in black pubertal adolescents compared with whites. This study aimed
      to investigate whether similar black/white differences are present in the
      prepubertal period or are characteristics of the pubertal period. Twelve black
      and 11 white healthy prepubertal children, matched for age, body mass index, and
      Tanner I pubertal development, underwent a 2-h hyperglycemic clamp (225 mg/dL).
      Physical fitness was assessed by maximal oxygen consumption (VO2max) measurement
      during graded bicycle ergometry, and resting energy expenditure was measured by
      indirect calorimetry after overnight fast. Fasting and first phase insulin
      concentrations were higher in blacks than in whites [14.7 +/- 1.3 vs. 10.4 +/-
      1.2 (P = 0.02) and 76.9 +/- 6.8 vs. 52.1 +/- 6.4 microU/mL (P = 0.016)]. There
      were no differences in second phase insulin levels and insulin sensitivity index.
      Both maximal oxygen consumption (VO2max) and resting energy expenditure were
      lower in black children, whereas insulin-like growth factor I was higher. After
      controlling for these differences, race contributed significantly to basal
      insulin, but not to first phase insulin. In summary, previously reported
      black/white differences in insulin secretion and sensitivity during adolescence
      may have their origin in early childhood manifested as hyperinsulinemia. However,
      genetic (race) vs. environmental factors (physical activity/fitness and energy
      balance) should be carefully scrutinized as potential factors responsible for
      such differences.

PMID- 9177408
TI  - Inhibin-B in the male rhesus monkey: impact of neonatal gonadotropin-releasing
      hormone antagonist treatment and sexual development.
AB  - We examined the effect of reversibly suppressing pituitary-testicular function
      during the neonatal period on developmental changes in inhibin-B and FSH
      secretion in male rhesus monkeys. Infants were treated with either vehicle, a
      GnRH antagonist (Ant) or the Ant and androgen (Ant/And) for the first 4 postnatal
      months, and the effects on serum inhibin-B and FSH were monitored during the
      neonatal and peripubertal periods. In neonates, Ant or Ant/And treatment lowered
      both serum FSH and inhibin-B levels. By 12 months of age, inhibin-B
      concentrations no longer differed across treatment groups. A major increase in
      inhibin-B occurred between 27-36 months of age (late prepubertal period) in all
      groups, but levels were lower at 33 and 36 months of age in Ant/And-treated
      animals than in controls. These differences most likely were related to fewer
      Ant/And-treated animals achieving sexual maturity during their fourth year of
      life. Regardless of treatment, inhibin-B levels were higher in those that were
      destined to become mature (in year 4) than in those that were not. During the
      late prepubertal period, serum inhibin-B was positively correlated with age and
      testicular volume, but not with serum LH or testosterone. After this period (39
      52 months of age), inhibin-B no longer correlated with these parameters. FSH
      levels were near or below detection limits in most peripubertal animals, but FSH
      was detectable in fewer samples from control than treated animals. The data
      suggest that inhibin-B secretion in the neonate is driven by gonadotropin
      secretion, but during the juvenile hiatus in gonadotropin secretion, the monkey
      testis continues to produce substantial amounts of this hormone.

PMID- 9177409
TI  - A 5'-splice site mutation in the cytochrome P450 steroid 17alpha-hydroxylase gene
      in 17alpha-hydroxylase deficiency.
AB  - 17alpha-Hydroxylase deficiency (17OHD) is an autosomal recessive disorder that
      produces an excess of mineralocorticoids and sexual differentiation
      abnormalities. Using DNA sequencing analysis of the 17alpha-hydroxylase (CYP17)
      gene from a Japanese patient with 17OHD, we identified a new type of genetic
      abnormality in this disease, a G to A transition at position +5 in the splice
      donor site of intron 7 of the CYP17 gene. In vitro expression analysis of an
      allelic minigene that consists of exons 6-8 of the patient's CYP17 gene showed
      that the transition causes the skipping of exon 7. This exon skipping alters the
      translational reading frame of exon 8 and introduces a premature stop codon (TAA)
      at amino acid position 410 proximal to the heme iron-binding site essential for
      the enzymatic activity of CYP17. Restriction enzyme analysis showed that the
      patient is homozygous for the mutated CYP17 gene, and the parents are
      heterozygotes. This is the first reported patient with 17OHD caused by the splice
      site mutation in the CYP17 gene.

PMID- 9177410
TI  - Serum alpha-inhibin levels in polycystic ovary syndrome: relationship to the
      serum androstenedione level.
AB  - To date, only one study has demonstrated increased serum inhibin levels in women
      with polycystic ovary syndrome (PCOS). Moreover, no relationship between serum
      inhibin and either FSH or androgen levels has been noted. This lack of data could
      be due to 1) the heterogeneity of PCOS and the small sample size of previous
      studies, and/or 2) the complexity of circulating inhibin molecular forms, which
      hinders the precise evaluation of bioactive inhibin. In the present study, alpha
      inhibin levels were assayed in the serum of 61 healthy women and 72 PCOS patients
      by means of an alpha-alpha enzyme-linked immunosorbent assay. Serum alpha-inhibin
      levels together with LH and androstenedione (A) levels were significantly
      increased in PCOS women (mean +/- SD, 1.45 +/- 0.55 vs. 0.94 +/- 0.36 U/mL in
      controls; P < 0.001). Moreover, simple and partial regression analysis
      demonstrated that serum A levels were positively and independently correlated to
      serum alpha-inhibin (r = 0.32; P < 0.01) and LH levels (r = 0.48; P < 0.001) in
      PCOS. The respective influences of alpha-inhibin and LH on A variability were 20%
      and 80%, as determined by multiple regression analysis. In conclusion, in
      agreement with recent in vitro data, our in vivo results argue for a role of
      inhibin in the hyperandrogenism of PCOS together with, but independently from,
      that of LH. Further studies are needed to determine whether this effect is
      produced by inhibin A and/or B.

PMID- 9177412
TI  - Expression of the apoptosis-suppressing gene BCL-2 in pheochromocytoma is
      associated with the expression of C-MYC.
AB  - It has become increasingly clear that deregulation of programmed cell death is a
      critical component in multistep tumorigenesis. Previous studies have demonstrated
      a high frequency of Bcl-2 expression in tumors arising from cells derived from
      the neural crest and in tumor cell lines of neural origin. The present
      investigation was undertaken to determine whether similar molecular events occur
      in human pheochromocytoma. With the aim of determining the potential role of
      apoptosis in the pathogenesis of this tumor, we assessed proto-oncogene Bcl-2 and
      c-myc protein products as well as Bcl-2 messenger RNA levels in a collection of
      such tumors. Western blot analysis revealed that such tumors expressed the 26 kDa
      Bcl-2 (5 of 8 cases) and the 64 kDa c-Myc (7 of 8 cases) proteins. Northern blot
      analysis detected the Bcl-2 transcripts in 6 of 8 tumors. Immunoperoxidase
      staining, using a monoclonal anti-Bcl-2 antibody, was positive in 18 (82%),
      including 5 malignant tumors, of the 22 specimens examined. This Bcl-2
      immunoreactivity was seen in 14 of 18 (78%) sporadic tumors, including 2 that
      were extra-adrenal, and all familial tumors. Of the 22 tumor samples examined for
      c-Myc protein, 20 (91%) tumors were positive. Our results suggest that
      deregulation of programmed cell death may be a critical component in the
      multistep tumorigenesis of human pheochromocytoma. The genetic complementation of
      simultaneously deregulated Bcl-2 and c-myc may be implicated in this process.

PMID- 9177411
TI  - Assessment of androgen receptor function in genital skin fibroblasts using a
      recombinant adenovirus to deliver an androgen-responsive reporter gene.
AB  - Mutations of the androgen receptor (AR) cause defects in virilization and can
      result in a spectrum of phenotypic abnormalities of male sexual development that
      includes patients with a completely female phenotype (complete testicular
      feminization) and individuals with less severe defects of virilization, such as
      Reifenstein syndrome. These phenotypes are not specific for mutations of the AR
      gene, however, and defects in other genes can also result in similar
      abnormalities of male development. For this reason, the diagnosis of an AR defect
      is laborious and requires data from endocrine studies, the family history, and in
      vitro binding experiments. To assist in the evaluation of patients with possible
      AR defects, we previously employed the use of a recombinant adenovirus to deliver
      an androgen-responsive gene into fibroblast cultures to assay AR function in
      normal subjects and patients with complete forms of androgen resistance. Although
      these studies demonstrated measurable differences between these two groups of
      subjects, we did not assay samples from patients with partial defects of androgen
      action. In the current study, we have modified this method to examine AR function
      in three groups of patients with known or suspected defects of AR function:
      patients with Reifenstein syndrome, patients with spinobulbar muscular atrophy,
      and patients with severe forms of isolated hypospadias. When assayed using this
      method, the AR function of patients with Reifenstein syndrome was intermediate
      between that of normal control subjects and that of patients with complete
      testicular feminization. Using the parameters established by the aforementioned
      experiments, we found that defective AR function can be detected in fibroblasts
      established from patients with spinobulbar muscular atrophy and in some patients
      with severe forms of isolated hypospadias, including two with a normal AR gene
      sequence. These results suggest that this method may have some utility in
      screening samples to detect defects of AR function, particularly when viewed in
      the context of other AR assays results.

PMID- 9177413
TI  - Changes in epitopes for thyroid-stimulating antibodies in Graves' disease sera
      during treatment of hyperthyroidism: therapeutic implications.
AB  - To determine whether there are changes in epitope recognition by stimulating TSH
      receptor antibodies (TSHRAbs) during treatment of hyperthyroidism and to evaluate
      the clinical relevance of such changes, we serially measured the activity of IgG
      preparations from 39 patients with Graves' disease over an 8-month period. To
      measure epitope changes of the stimulating TSHRAbs, we used Chinese hamster ovary
      (CHO) cells transfected with wild-type human TSHR (hTSHR) or TSHR chimeras with
      residues 90-165 (Mc2) substituted by equivalent residues of the rat LH/CG
      receptor. When initially examined, 37 of the 39 patients had significant
      stimulating TSHRAb activity measured with wild-type CHO-hTSHR cells. Serial
      measurements of stimulating TSHRAb activity in Mc2 chimera-transfected cells
      divided the 39 patients into three distinct groups. Thus, 10 patients
      (heterogeneous epitope group) exhibited low but significant activity in Mc2
      chimera assays at the start of the study; 10 patients who were initially negative
      in Mc2 chimera assays remained negative (persistently homogeneous epitope group);
      and 19 patients who were initially negative in Mc2 chimera assays became
      transiently or persistently positive during treatment, despite a simultaneous
      decrease in TSHRAb activity measured with wild-type TSHR (changing epitope
      group). The functional stimulating TSHRAb epitope thus changed from residues 90
      165 to residues outside this region in the last group, which comprises nearly two
      thirds of the initially Mc2-negative patients (19 of 29) and one-half of all
      patients (19 of 39). Patients in the changing epitope group responded more
      quickly and to lower doses of methimazole than patients in the persistently
      homogeneous epitope group, behaving in this respect exactly as the patients in
      the heterogeneous epitope group. Additionally, although the decrease in
      stimulating TSHRAb activities during the 8-month treatment period was similar in
      the two groups, the thyrotropin binding inhibitor immunoglobulin (TBII)
      activities decreased more rapidly in patients in the persistently homogeneous
      epitope group than in patients in the changing epitope group (P < 0.05). There
      were no differences in initial stimulating TSHRAb or TBII activities, degree of
      hyperthyroidism, goiter size, or prior duration of symptoms between the
      persistently homogeneous epitope group and changing epitope group. In summation,
      we show that the epitopes of stimulating TSHRAbs in Graves' disease patients may
      change during their clinical course or treatment period, and that the change is
      from antibodies recognizing N-terminal TSHR residues 90-165 to antibodies
      recognizing other regions of the TSHR. We also show that the development of
      stimulating TSHRAbs with this heterogeneous epitope or their presence at the
      initial screening for disease activity seems to be associated with increased
      responsiveness to antithyroid drug therapy. We suggest, therefore, that Mc2
      chimera assays may be useful to predict the response of patients to antithyroid
      drug therapy.

PMID- 9177414
TI  - Thyroid hormone and estrogen receptor expression in normal pituitary and
      nonfunctioning tumors of the anterior pituitary.
AB  - Nonfunctioning tumors (NFTs) of the anterior pituitary often express elevated
      levels of the glycoprotein hormone alpha-subunit, which, under normal
      physiological conditions, is under negative feedback control by thyroid and
      gonadal steroid hormones. We postulate that inappropriately elevated levels of
      expression of alpha-subunit in the face of normal levels of these target organ
      hormones may reflect an abnormality of thyroid hormone receptors (TRs) and/or
      gonadal steroid receptors in NFTs. Using immunocytochemistry and Western blotting
      we have examined TR and estrogen receptor (ER) protein expression in normal human
      anterior pituitary glands and NFTs. Pretranslational expression of these
      receptors was examined using semiquantitative reverse transcriptase-PCR.
      Expression of all TR variant and ER proteins was reduced in pituitary tumors
      compared with that in normal pituitaries. The expression of messenger ribonucleic
      acids encoding the TR beta1 and TR beta2 isoforms and ER was also significantly
      reduced in tumors compared with normal tissues, although there was no difference
      between tumors and normals in the level of expression of TR alpha1 and alpha2
      messenger ribonucleic acids. We suggest that reduced expression of TRs and ER may
      account for inappropriate expression of the glycoprotein hormone alpha-subunit
      gene in some NFTs and may contribute to uncontrolled tumor growth.

PMID- 9177415
TI  - Increased concentration of vascular endothelial growth factor/vascular
      permeability factor in cyst fluid of enlarging and recurrent thyroid nodules.
AB  - Human thyrocytes produce vascular endothelial growth factor (VEGF), a potent
      angiogenic factor, also known as vascular permeability factor (VPF), which
      increases vascular permeability. Based on the assumption that VEGF/VPF is
      involved in fluid accumulation in thyroid cysts, we determined the VEGF/VPF
      concentration in cyst fluids of thyroid nodules from 79 patients. VEGF/VPF was
      found to be abundantly present in the cyst fluids (0.02-183 ng/mL). There was no
      significant difference of VEGF/VPF concentration in the cyst fluid obtained from
      thyroid adenoma or from adenomotous goiter with cystic degeneration.
      Immunoreactive VEGF/VPF in cyst fluid was eluted mainly at 45 kDa, and stimulated
      endothelial cell proliferation, which was partially blocked by anti-VEGF/VPF
      antibody. The VEGF/ VPF concentration in the cyst fluid obtained from patients
      who required repeated aspiration or underwent surgical resection because of
      recurrent accumulation (84.8 +/- 58.3 ng/mL, mean +/- SD, n = 18) was
      significantly higher than that in the cysts that regressed or disappeared after a
      single aspiration (4.3 +/- 4.4 ng/mL, n = 12, P < 0.001). These in vitro and
      clinical findings suggest that VEGF/VPF is at least partly involved in the
      accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF
      concentration predicts rapid accumulation of the cyst fluid, possibly
      necessitating interventional treatment.

PMID- 9177416
TI  - Gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor
      messenger ribonucleic acids expression in nontumorous and neoplastic pituitaries.
AB  - In the nontumorous pituitary, GnRH stimulates the release and synthesis of LH and
      FSH by gonadotroph cells via the GnRH receptor (GnRH-R). Little is known,
      however, about expression of GnRH and GnRH-R messenger RNAs (mRNAs) in
      nontumorous pituitary tissue and in adenomas. To learn more about the
      distribution and regulatory roles of GnRH and its receptor, we investigated the
      expression of both GnRH and GnRH-R mRNAs in nontumorous human pituitary and in
      various types of pituitary adenomas using the RT-PCR, in situ hybridization, and
      in situ hybridization in combination with RT-PCR (in situ RT-PCR). Using RT-PCR,
      GnRH mRNA was found to be expressed in normal human pituitaries and in all types
      of adenomas. Similarly, GnRH-R mRNA was expressed in nontumorous human
      pituitaries and in most, but not all, adenomas. These included 5 gonadotroph
      adenomas, 6 null cell adenomas, 1 of 2 GH-producing tumors, and 1 of 2 ACTH
      producing adenomas, but not in the 2 PRL-producing adenomas examined. In situ
      hybridization studies showed GnRH and GnRH-R mRNAs in all 3 nontumorous
      pituitaries and in 12 of 33 (36.4%) and 10 of 33 adenomas (30.3%), respectively.
      Using an indirect in situ RT-PCR technique to increase the sensitivity of the in
      situ localization, GnRH and GnRH-R mRNAs were detected in 29 (87.9%) and 25
      (75.8%) of 33 adenomas, respectively. This is the first report of the
      localization of GnRH and GnRH-R mRNAs in individual pituitary adenoma cells using
      in situ RT-PCR. The frequent expression of GnRH and GnRH-R mRNAs in pituitary
      cells suggests that GnRH has autocrine/paracrine functions in nontumorous and
      neoplastic pituitary tissues.

PMID- 9177417
TI  - Alterations in endometrial stromal cell tissue factor protein and messenger
      ribonucleic acid expression in patients experiencing abnormal uterine bleeding
      while using Norplant-2 contraception.
AB  - A high incidence of irregular uterine bleeding is the primary patient complaint
      limiting the utility of long term, progestin-only contraceptive agents such as
      Norplant. The onset of hemorrhage requires both inadequate hemostasis and
      impaired vascular integrity. Thus, we first tested whether Norplant-associated
      endometrial bleeding was accompanied by altered expression of perivascular
      stromal cell tissue factor (TF), the primary initiator of hemostasis. Norplant
      effects on TF messenger ribonucleic acid (mRNA) and protein expression by
      endometrial stromal cells were assessed by in situ hybridization and
      immunohistochemical examination of endometrial biopsies obtained from normally
      cycling control women (n = 14) and from patients experiencing Norplant-induced
      abnormal uterine bleeding (n = 24). TF mRNA and protein expression was increased
      150% in secretory vs. proliferative phase endometrial specimens. By contrast,
      endometrial TF mRNA and protein levels were reduced during 1-6 months of Norplant
      treatment by about 2-fold (P < 0.05 for protein) compared to the values for
      control secretory phase specimens. These changes were consistent with
      observations that patients on Norplant begin to bleed during this interval.
      Further reductions of TF mRNA and protein levels to 2- and 3-fold of those in
      secretory phase control specimens were observed in endometria obtained after 6-12
      months of Norplant therapy (P < 0.05 and P < 0.01, respectively). A modest
      rebound in TF mRNA and protein expression was observed after 12 months of
      Norplant therapy, which occurred commensurate with reduced patient complaints of
      abnormal uterine bleeding. Pathologically enlarged venous sinusoids were
      ubiquitous in endometrial specimens obtained after Norplant therapy. The
      combination of fragile blood vessels and reduced TF expression may account for
      bleeding in patients receiving Norplant therapy.

PMID- 9177418
TI  - Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and
      mineral metabolism.
AB  - The effect of antiresorptive therapy with nasal calcitonin (CT) in recently
      diagnosed hyperthyroid patients on conventional medical therapy as well as the
      evolution of bone metabolism were assessed. Forty-five patients with recent-onset
      hyperthyroidism (<12 weeks) were sex and menopause stratified and randomly
      allocated to treatment with carbimazole (Neotomizol), carbimazole plus low dose
      CT (Calsynar; 100 IU/day, 2 days/week), or carbimazole plus high dose CT
      (Calsynar; 100 IU/day, 14 days/month). Bone mineral density was measured by dual
      x-ray absorptiometry in lumbar spine, femoral neck, and Ward's triangle at 0, 9,
      and 18 months of treatment. We also determined free T4, free T3, TSH,
      osteocalcin, total and bone alkaline phosphatases, tartrate-resistant acid
      phosphatase, type I collagen C telopeptide, and urinary hydroxyproline every 3
      months of follow-up. No significant difference was observed among treatments. A
      euthyroid state was attained at 3 months. Bone mass increased significantly at
      the 9 month evaluation (P < 0.05), with a 5-10% net gain during follow-up.
      Nevertheless, final bone mass was 4-8% smaller than expected. Bone formation
      markers were increased at 0 and 3 months, with reductions at 6-9 months;
      resorption bone markers showed a significant reduction at the 3 month evaluation.
      These results indicate that the euthyroid state partially reduces hyperthyroidism
      associated osteopenia, with a bone mass recovery period during the 6-9 early
      months of effective treatment. This recovery phase is characterized by raised
      bone formation markers and reduced bone resorption markers. The treatment with
      nasal CT at the doses assayed has no additional effect over that of attainment of
      the euthyroid state.

PMID- 9177419
TI  - Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain
      and skull-based tumors.
AB  - The objective of this study was to determine whether a low dose of ACTH (0.2
      microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic
      pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and
      skull-based tumors. Twenty-two children who had undergone treatment for brain or
      skull-based tumors were enrolled in a prospective study to extensively evaluate
      the HPA axis. Five tests of the adrenal axis were evaluated in each patient,
      including determination of basal serum cortisol, a standard ACTH test (250-microg
      i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin
      tolerance test, and a single dose metyrapone test. Cortisol responses to both
      ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH
      test, whereas three (14%) failed the standard ACTH test; five of the children
      (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to
      metyrapone. One child who initially passed the metyrapone test failed the test 19
      months later after becoming symptomatic. All children with abnormal metyrapone
      test results had low levels of basal cortisol secretion. In this study, the low
      dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of
      the HPA axis. We conclude that a single morning basal cortisol level is a good
      screen for testing the HPA axis in children. We recommend confirming HPA axis
      dysfunction with the single dose metyrapone test, although this test also has
      limitations.

PMID- 9177420
TI  - Beneficial effect of pentoxifylline on thyroid associated ophthalmopathy (TAO)*:
      a pilot study.
AB  - We have previously found that pentoxifylline (Ptx) inhibited cytokine induced HLA
      DR expression and glycosaminoglycan (GAG) synthesis by retroorbital fibroblasts.
      We have now tested the clinical efficacy of Ptx in treating TAO. Ten patients
      with moderately severe ophthalmopathy were selected for study. All patients were
      euthyroid before and during the 12 weeks of the Ptx therapy. Serum GAG, TNF
      alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid
      peroxidase antibodies were determined sequentially. At the end of 12 weeks eight
      of the ten patients showed improvement in soft tissue but not in proptosis or
      extraocular muscle involvement. At baseline the levels of GAG (5.2+/-0.92 mg/dl
      v.s. 0.7+/-0.14 mg/dl, p<0.001) and TNF-alpha (33.6+/-6.6 pg/ml v.s. 5.4+/-1.3
      pg/ml, p<0.001) were increased in patients compared to controls. They gradually
      decreased in the eight patients who responded to Ptx: after 4, 8 and 12 weeks of
      therapy serum GAG was 3.4+/-0.42 mg/dl, 2.5+/-0.77 mg/dl (p<0.01) and 1.1+/-0.2
      mg/dl (p<0.001), respectively and serum TNF-alpha was 20.9+/-4.8 pg/ml, 14.9+/
      2.2 pg/ml (p<0.05) and 9.7+/-1.8 pg/ml (p<0.01), respectively. Serum GAG and TNF
      alpha did not fall in the two patients who did not respond. The titre of anti-eye
      muscle antibodies but not anti-thyroid antibodies were lower at 12 weeks. Ptx has
      a beneficial effect on inflammatory symptoms of TAO and associated laboratory
      parameters in the majority of patients.

PMID- 9177421
TI  - Thyrotropin receptor transcripts in human adipose tissue.
AB  - Thyroid associated ophthalmopathy (TAO) is generally considered to have an
      autoimmune pathogenesis but the target antigen has yet to be identified. It is
      most frequently associated with Graves' disease and there is some logic in
      assuming that the same antigen, the thyrotropin receptor (TSHR), is the common
      link. Previous studies, mostly PCR based, aimed at investigating TSHR transcripts
      in the orbit, have yielded conflicting results, although there is circumstantial
      evidence for their presence in orbital fat. In this study, we have examined adult
      human adipose and muscle tissues from various locations, initially by PCR and
      subsequently by northern blot. We obtained the expected 610bp product in normal
      intestinal and orbital fat but not skeletal muscle, following two rounds of PCR
      amplification but only when reverse transcription used a TSHR specific primer. In
      northern blots, despite loading all of the RNA obtained from total normal orbital
      fat contents, TSHR transcripts were at the limit of detection and similarly for
      large samples of intestinal fat. The exception was RNA obtained from TAO orbital
      fat, in which TSHR transcripts of 4.6 and 1.7kb were clearly visible, as in the
      thyroid. We conclude that normal adult adipose tissues contain low levels of TSHR
      transcripts. In TAO, TSHR transcripts are elevated probably due to an increased
      number of cells, in particular of preadipocytes in orbital adipose tissue.

PMID- 9177422
TI  - Differential expression of messenger ribonucleic acids encoding 11beta
      hydroxysteroid dehydrogenase types 1 and 2 in human granulosa cells.
AB  - In glucocorticoid target organs 11beta-hydroxysteroid dehydrogenase (11betaHSD)
      regulates the levels of active glucocorticoids available to glucocorticoid
      receptors. To date two isoforms of 11betaHSD, NADP-dependent type 1 11betaHSD
      (11betaHSD1) with predominant reductase activity and NAD-dependent type 2
      11betaHSD (11betaHSD2) with dehydrogenase activity have been identified. Human
      ovarian granulosa cells have been shown to possess both dehydrogenase and
      reductase 11betaHSD activities and express 11betaHSD1 mRNA. However, whether
      11betaHSD2 mRNA is also present or if the expression of either mRNA is
      developmentally regulated in the human ovary is unknown. We therefore used
      northern analysis to examine 11betaHSD1 and 11betaHSD2 mRNA levels in non
      luteinized and luteinizing granulosa cells, corpora lutea (CL) and ovarian stroma
      obtained from human ovaries. Here we show that non-luteinized granulosa cells
      express relatively high levels of 11betaHSD2 mRNA but not 11betaHSD1. Conversely,
      luteinizing granulosa cells abundantly express 11betaHSD1 mRNA but not
      11betaHSD2. CL also expresses 11betaHSD2 to lesser extent. Neither 11betaHSD mRNA
      is detectable in ovarian stroma. These results indicate that mRNAs encoding both
      1lbetaHSD isozymes are present in human granulosa cells and they are
      developmentally--but differentially--regulated during preovulatory follicular
      development. The existence of developmentally regulated 11betaHSD in human
      granulosa cells is important new evidence that glucocorticoids, acting directly
      on the ovary, serve physiologically significant roles in the regulation of
      folliculogenesis.

PMID- 9177423
TI  - Abnormalities of very low density lipoprotein apolipoprotein B-100 metabolism
      contribute to the dyslipidaemia of adult growth hormone deficiency.
AB  - Increased cardiovascular mortality in adult growth hormone deficiency (GHD) may
      be, in part, explained by the dyslipidaemia associated with this condition. It is
      possible that abnormalities of very low density lipoprotein apolipoprotein B-100
      (VLDL apoB) metabolism contribute to this dyslipidaemia. To test this hypothesis,
      we measured VLDL apoB kinetics in adult GH deficient patients (4 females, 3
      males; age 50.1 +/- 4.7 yr (mean +/- SEM); BMI 28.2 +/- 1.1 kg/m2; total
      cholesterol (TC) 6.6 +/- 0.3 mmol/l; triglyceride (TG) 2.8 +/- 0.6 mmol/l; HDL
      cholesterol 1.1 +/- 0.1 mmol/l) and in control subjects (4 females, 3 male; age
      47.0 +/- 4.7 yr; BMI 27.0 +/- 2.6 kg/m2; TC 5.0 +/- 0.4 mmol/l; TG 0.9 +/- 0.2
      mmol/l; HDL cholesterol 1.4 +/- 0.1 mmol/l). [1-(13)C] leucine was administered
      by a primed (1 mg/kg), constant intravenous infusion (1 mg/kg/hr) and VLDL apoB
      enrichment with 13C leucine was determined using gas-chromatography mass
      spectrometry. The GHD patients had a significantly higher hepatic secretion rate
      of VLDL apoB (15.5 +/- 1.8 mg/kg/day vs 9.4 +/- 0.6 mg/kg/day p = 0.007) and
      reduced catabolism ofVLDL apoB (metabolic clearance rate; 12.3 +/- 1.7 ml/min vs
      24.3 +/- 4.8 ml/min p < 0.05) compared with control subjects. These findings
      suggest that GH is integrally involved in the regulation of VLDL apoB metabolism.

PMID- 9177424
TI  - Errors in the measurement of plasma free testosterone.

PMID- 9177425
TI  - Thyroid cancer and the Chernobyl accident. Are long-term and long distance side
      effects of fall-out radiation greater than estimated?

PMID- 9177426
TI  - Chronic lymphocytic leukemia: a changing natural history?
AB  - There are some data suggesting that the natural history of chronic lymphocytic
      leukemia (CLL) may be changing, but a systematic analysis of this topic is
      lacking. To address this issue, we examined two cohorts of CLL patients in whom
      the diagnosis was established in 1960-1979 (group I) and in 1980-1989 (group II),
      respectively. Striking differences were observed between both cohorts. The
      diagnosis in the second group was established at higher age (65.8 vs 61.3 years;
      P = 0.0001), both in males (63.8 vs 59.1 years; P = 0.004) and females (68.3 vs
      64.2 years; P = 0.01); the proportion of patients in whom the diagnosis was
      established in low-risk clinical stage (Binet's A) was significantly higher in
      group II (65.7% vs 42.6%; P < 0.001), and the survival was more than double in
      group II (median of 11.1 vs 5.3 years; P < 0.0001). Moreover, the impact of the
      disease on life expectancy was much lower in the more recent cohort. These
      differences may be due, at least in part, to changes in the natural history of
      the disease.

PMID- 9177428
TI  - Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin
      and fludarabine.
AB  - In vitro studies suggest that nucleoside analogs have an antileukemic effect
      against chronic myelogenous leukemia (CML). We investigated the antileukemia
      effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four
      patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at
      4 mg/m2 every week for 4 weeks, then every other week for four doses, and then
      every month as maintenance. Two patients were in late chronic phase and two in
      accelerated phase. All had previously failed therapy with interferon-alpha (IFN
      A). Nine patients were treated with fludarabine 30 mg/m2/day for 5 days every 28
      days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were
      in accelerated phase and four in late chronic phase. Three patients treated with
      DCF had normalization of WBC counts while on the weekly schedule but progressed
      when changed to every other week. The fourth patient had no objective response.
      There were no cytogenetic responses. DCF was well tolerated with only mild nausea
      and vomiting in all patients. Patients treated with fludarabine received a median
      of two courses (range 1-4). In two patients (both Ph-positive), disease
      progressed to blastic phase upon recovery. Two other patients died of hemorrhagic
      complications secondary to thrombocytopenia. In all other cases fludarabine
      produced a transient reduction of WBC counts, but counts recovered to levels
      equal to or greater than the pre-treatment values. There were no cytogenetic
      responses. These results, together with previous experience with 2-CDA producing
      only hematologic responses, suggest that nucleoside analogs may not have a
      significant role in the management of CML.

PMID- 9177427
TI  - Vitamin K2 and its derivatives induce apoptosis in leukemia cells and enhance the
      effect of all-trans retinoic acid.
AB  - Geranylgeraniol, a polyprenylalcohol composing the side chain of vitamin K2
      (VK2), was previously reported to be a potent inducer of apoptosis in tumor cell
      lines (Ohzumi H et al, J Biochem 1995; 117: 11-13). We examined the apoptosis
      inducing ability of VK2 (menaquinone 3 (MK3), MK4 and MK5) and its derivatives
      such as phytonadione (VK1), as well as polyprenylalcohols with side chains of
      various lengths including farnesol (C15-OH; FO), geranylgeraniol (C20-OH; GGO),
      and geranylfarnesol (C25-OH; GFO) toward leukemia cells in vitro. MK3, MK4, MK5
      and GFO (at 10 microM) showed a potent apoptosis-inducing activity for all
      freshly isolated leukemia cells tested and for leukemia cell lines such as NB4,
      an acute promyelocytic leukemia (APL)-derived cell line and MDS92, a cell line
      derived from a patient with myelodysplastic syndrome, although there were some
      differences depending on the cells tested. In contrast, VK1 showed no effect on
      any of the leukemia cells. The combination of MK5 plus all-trans retinoic acid
      (ATRA) resulted in enhanced induction of apoptosis in both freshly isolated APL
      cells and NB4 cells as compared to each reagent alone. These data suggest the
      possibility of using VK2 and its derivatives for the treatment of myelogenous
      leukemias, including APL.

PMID- 9177429
TI  - Dental abnormalities in children treated for acute lymphoblastic leukemia.
AB  - The purpose of this study was to define the therapy-associated dental
      abnormalities in survivors of acute lymphoblastic leukemia (ALL). We reviewed the
      clinical records and panoramic radiographs of 423 survivors of ALL who were
      treated on one of four consecutive protocols (1975-1991). Dental abnormalities
      included root stunting, microdontia, hypodontia, taurodontia (enlarged pulp
      chambers), and over-retention of primary teeth. The frequency of these factors
      was determined in relation to age at initiation of treatment (< or = 8 years vs >
      8 years), addition of cranial irradiation, and chemotherapeutic protocol. A total
      of 423 patients met the study criteria. The abnormalities comprised root stunting
      in 24.4% (n = 103), microdontia in 18.9% (n = 80), hypodontia in 8.5% (n = 36),
      taurodontia in 5.9% (n = 25), and over-retention of primary dentition in 4.0% (n
      = 17). Patients who were < or = 8 years old at diagnosis or who received cranial
      irradiation therapy developed more dental abnormalities than did those > 8 years
      and those who did not receive cranial irradiation (42 vs 32%). Survivors of
      childhood ALL often have dental abnormalities that may affect their quality of
      life. Dental evaluation at diagnosis and frequent follow-up may help to ensure
      appropriate preventive measures and minimize dental and periodontal disease.

PMID- 9177430
TI  - Microsatellite instability in childhood T cell acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most frequent cancer encountered in
      children. Little is known about the molecular pathology of childhood T cell ALL.
      Oncogenesis is a multistep process that involves alterations in proto-oncogenes
      and tumor suppressor genes. Recently, a mutator phenotype detectable by
      microsatellite instabilities was shown to be associated with predisposition to
      cancer. This new mechanism for human carcinogenesis is caused by defects in the
      DNA replication/repair system. To study the involvement of some of these
      mutational events in the development of T cell ALL, we have initiated a
      systematic search for losses of heterozygosity (LOH) and microsatellite
      instabilities in children affected with this disease. These patients were
      allelotyped by PCR using 56 microsatellite markers located near known or putative
      tumor suppressor genes. The microsatellite patterns were altered in more than 80%
      of the patients. LOH were detected in chromosomes 6p, 12p and 9p. Two third of
      the patients were deleted for chromosome 9p21, suggesting the involvement of a
      tumor suppressor gene, probably the p16 gene. The only patient refractory to
      chemotherapy was shown to be associated with a mutator phenotype. This is the
      first documented case of a childhood neoplasia associated with genomic
      instabilities. Our results suggest that defects in DNA replication/repair
      components are involved in the development of a subset of childhood T cell ALL.

PMID- 9177431
TI  - Prognostic significance of immunoglobulin heavy chain gene rearrangement in
      patients with acute myelogenous leukemia.
AB  - Recently the immunoglobulin heavy chain (IgH) gene rearrangement in B cell
      malignancies has been analyzed. Clonality can be determined using the polymerase
      chain reaction (PCR). Little attention, however, has been given to the
      relationship between prognosis and IgH gene rearrangement in patients with acute
      myelogenous leukemia (AML). In this study, we examined IgH gene rearrangement in
      35 untreated AML patients by PCR. PCR was performed using consensus heavy chain
      complimentarity-determining region (CDR)-3 primers. Clonal IgH gene rearrangement
      was detected in 14 patients (40%). Four of five patients (80%) who were positive
      for B cell markers had clonal IgH gene rearrangement. Ten of 30 B cell antigen
      negative patients (33%) also showed IgH rearrangement. All patients were treated
      with a daunorubicin-based regimen, resulting in complete remission for 29
      patients (83%). Sixty-four percent of those with IgH rearrangement and 95% of
      those without rearrangement had complete remission. Overall survival of IgH-PCR
      positive and negative patients at 25 months was 29 and 88%, respectively. IgH-PCR
      positivity may be a poor prognostic factor in AML.

PMID- 9177432
TI  - Mini- and microsatellite mutations in radiation-induced acute myeloid leukaemia
      in the CBA/H mouse.
AB  - Radiation-induced acute myeloid leukaemia (AML) in the CBA/H mouse is a clonal
      disorder and therefore amenable to the analysis of genetic instability during
      radiation leukaemogenesis. The genotype of a single minisatellite and 20
      microsatellite loci was compared in tail and leukaemic spleen DNA prepared from
      the same mouse. Somatic mutation at the Ms6-hm minisatellite locus was nearly
      seven times higher (27%, 4/15) than the spontaneous germline mutation rate (4%).
      Only 1/15 AMLs exhibited microsatellite mutations, but 5/20 loci were mutated in
      the same AML, indicating that it was deficient in mismatch repair. Thus, whereas
      somatic minisatellite mutations, which are associated with complex intra-allelic
      gene conversion events, occur at a very high rate in the radiation-induced AMLs,
      microsatellite instability, which has been associated with the acquisition of the
      replication error repair (RER+) phenotype, is infrequent but detectable.

PMID- 9177433
TI  - Effect of bcr-abl oligodeoxynucleotides on the clonogenic growth of chronic
      myelogenous leukaemia cells.
AB  - We studied the effect of phosphorothioate oligodeoxynucleotides ([S]ODNs)
      complementary to the bcr-abl junction on cells taken at diagnosis from 41
      patients with Philadelphia-positive chronic myelogenous leukaemia (CML).
      Experiments included the evaluation of the anti-leukaemic effect of 16- and 26
      mer antisense [S]ODNs on both mononuclear and CD34+ cells, evaluation of
      incubation time and correlation of colony growth inhibition with the down
      regulation of p210(bcr-abl). At the same time, the uptake of [S]ODNs by
      mononuclear and purified CD34+ cell populations and the cross-hybridization of 26
      and 16-mer [S]ODNs with the complementary sequences were evaluated. After
      incubation for 120 h with 26-mer antisense [S]ODNs on mononuclear cells, overall
      mean colony recovery was 41.9% of the untreated control samples; in particular, a
      significant reduction in colony formation was observed in 22 of the 35 cases
      tested. The effect of 26-mer ODNs on CD34+ cells was comparable to that observed
      on mononuclear cells in terms of colony inhibition; however, a higher proportion
      of cases showed a significant inhibition of colony formation. In comparison with
      the 26-mer antisense [S]ODNs, the anti-leukaemic effect of the 16-mer antisense
      [S]ODNs was less evident on mononuclear cells and comparable on CD34+ cells;
      however, a more specific effect was evident on both target cells. Hybridization
      experiments confirmed a partial cross-reactivity when the 26-mer ODNs were
      hybridized with their complementary sequence; this did not occur when 16-mer ODNs
      were similarly tested. Experiments aimed at evaluating the effect of the
      incubation time showed a significant increase in anti-leukaemic effect after a
      120 h incubation period compared to that measured after a 24 h incubation period;
      this was parallelled by a progressive increase in the intracellular
      concentrations of [S]ODNs from day 1 to day 5. The accumulation of [S]ODNs
      correlated with a marked down-regulation of p210(bcr-abl) levels which was first
      detectable after 72 h of treatment. The down-regulation of p210(bcr-abl) levels
      following treatment with [S]ODNs showed a correlation between the effect of
      antisense [S]ODNs on leukaemic colony formation and protein expression. These
      studies confirm that, under optimal conditions of target cell culture and ODN
      size, antisense [S]ODNs complementary to the bcr-abl junction have specific anti
      leukaemic effects.

PMID- 9177434
TI  - The common TEL/AML1 rearrangement does not represent a frequent event in acute
      lymphoblastic leukaemia occuring in children with Down syndrome.
AB  - Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk
      of developing acute leukaemias, both of myeloid and lymphoid lineage. Although
      the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate
      genes include the ones on chromosome 21, and in particular AML1, the
      rearrangement of which in the t(8,21) is associated with the French-American
      British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the
      general population and has been described in Down patients with AML-M2. Recently,
      a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid
      transcript, has been described by molecular analysis as the most recurrent
      genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to
      investigate whether the t(12;21) could give a molecular clue as to the precise
      basis of the etiologic association between DS and acute lymphoblastic leukemia,
      we tested a series of 11 consecutive cases of ALL in DS children for the presence
      of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1
      rearrangement among the 11 cases tested. This data may be suggestive of
      alternative pathways involved in the pathogenesis of ALL in children with
      constitutional trisomy 21.

PMID- 9177435
TI  - Activation of beta1 integrins on CML progenitors reveals cooperation between
      beta1 integrins and CD44 in the regulation of adhesion and proliferation.
AB  - Adhesion of normal colony-forming cells (CFC) to bone marrow (BM) stroma and the
      extracellular matrix (ECM) component fibronectin (FN) depends at least in part on
      the alpha4beta1 and alpha5beta1 integrins and the CD44 receptor. Aside from
      anchoring progenitors in the marrow microenvironment, beta1 integrin-dependent
      adhesion of normal CFC is associated with inhibition of their proliferation. In
      contrast to normal CFC, chronic myelogenous leukemia (CML) Ph+ CFC adhere
      significantly less to either stroma or FN. CML Ph+ CFC proliferation is also not
      inhibited by coculture with stroma or FN. However, equal numbers of alpha4,
      alpha5, and beta1 integrins and CD44 are present on CML and normal CD34+ cells.
      We have previously demonstrated that beta1-dependent adhesion to and subsequent
      proliferation inhibition by FN can be restored when CML Ph+ CFC are incubated
      with the beta1 integrin activating antibody, 8A2, and demonstrated a role for the
      alpha5beta1 integrin in this phenomenon. Since the integrin alpha4beta1 and the
      proteoglycan form of CD44 may cooperate in establishing normal CFC adhesion to
      FN, we examined if treatment of CML Ph+ CFC with 8A2 also restores the
      cooperativity between beta1 integrins and CD44. We demonstrate that 8A2 induces
      adhesion of CML Ph+ CFC not only to intact FN but also to alpha4beta1,
      alpha5beta1, and proteoglycan binding fragments of FN. 8A2-induced adhesion to
      these fragments and peptides also results in a significant inhibition of the
      proliferation of CML Ph+ CFC. Addition of antibodies to either the alpha5,
      alpha4, or beta1 integrins, antibodies against the CD44 receptor, or removal of
      chondroitin sulfate glycosaminoglycans from the surface of CML CD34+ HLA-DR+
      cells significantly reduced the 8A2-induced adhesion to and adhesion-mediated
      inhibition of proliferation by FN. These studies demonstrate that activation of
      beta1 integrins on CML Ph+ CFC not only results in upregulation of beta1 integrin
      dependent adhesion and adhesion-mediated inhibition of proliferation, but also in
      the restoration of cooperation between beta1 integrins and CD44. These studies
      suggest that decreased beta1 integrin avidity may also affect the function of the
      proteoglycan adhesion receptor CD44, both of which may contribute to the abnormal
      circulation and expansion of malignant progenitors in CML.

PMID- 9177436
TI  - CD34+ megakaryoblastic leukaemic cells are CD38-, but CD61+ and glycophorin A+:
      improved criteria for diagnosis of AML-M7?
AB  - The aim of this flow cytometry study in acute megakaryoblastic leukaemia (AML-M7)
      was to describe the membrane phenotype of CD34+ progenitor subsets and compare
      these with the phenotypes expressed by other AML FAB types. Following
      conventional histopathological diagnosis mononuclear cells from bone marrow and
      blood were examined in seven patients with AML-M7 and compared with results from
      26 sequential patients with AML-M0 to AML-M6. The CD34+ subsets in AML-M7
      patients differed from that of patients with AML-M0 to AML-M6 as the CD34+ CD61+
      and the CD34+ Glycophorin A+ subsets were median 31% and 20%, respectively,
      compared to 4% and 2% in the AML-M0 to AML-M6 (P = 0.0005). Only 1% of the CD34+
      progenitors were CD34+ CD38+ in AML-M7 compared to 72% in other AML subtypes (P <
      0.000). These findings suggest that the CD34+ cell compartment in AML-M7 consists
      of early lineage-specific progenitors. In conclusion, flow cytometry analysis of
      CD34+ subsets may improve the diagnostic safety in AML-M7 and consequently the
      prognostic significance of immunophenotyping in acute leukaemia.

PMID- 9177437
TI  - Cytomegaloviremia after autografting for leukemia: clinical significance and lack
      of effect on engraftment.
AB  - One hundred and fourteen patients with leukemia (66 cytomegalovirus (CMV)
      seropositive and 48 CMV-seronegative) were monitored for cytomegaloviremia by
      early antigen detection or conventional viral culture after autologous stem cell
      transplantation (ASCT). Twenty-two episodes of viremia were seen at 2-36 weeks
      (median 11) in 14 seropositive patients. Nineteen resolved without therapy in 11
      patients. Three patients with clinical features suggestive of CMV disease were
      treated with ganciclovir: viremia resolved prior to ganciclovir in one, and with
      3 weeks of ganciclovir in the other two. Transient thrombocytopenia (n = 4) and
      leukopenia (n = 1) were seen in association with five episodes of viremia. The
      counts recovered in all five patients; with ganciclovir (n = 2) or with
      spontaneous clearance of viremia (n = 3). One seronegative patient developed
      viremia which resolved spontaneously in 3 weeks. No symptoms suggestive of CMV
      disease were seen in any of the other patients. CMV serostatus or development of
      CMV infection did not affect hematologic recovery. In our experience,
      cytomegaloviremia is relatively uncommon after autografting for leukemia, and
      usually does not require treatment. We now do not routinely monitor leukemia
      patients for CMV infection after autografting, but look for viremia in CMV
      seropositive patients with unexplained fever, drop in blood counts, lung
      infiltrates, or gastrointestinal symptoms.

PMID- 9177438
TI  - Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic
      syndromes.
AB  - Apoptosis of hematopoietic progenitor cells is increased in myelodysplastic
      syndromes (MDS). We have studied Fas (CD95/Apo-1) antigen expression in 27 MDS
      patients (RARS 4, RA 3, RAEB 13; RAEB-t 3, CMML 4) and three AML secondary to
      MDS. We found that the Fas antigen was not expressed on normal bone marrow (BM)
      CD34+, CD14+, or glycophorin+ cells, and only slightly on CD33+ cells. Patients
      with MDS had upregulation of Fas expression on total bone marrow nuclear cells
      (BMMC) (t-test, P = 0.04), CD34+ (P = 0.013), CD33+ (P = 0.04), and glycophorin+
      (P = 0.032) BM cells compared to controls. Fas expression did not correlate to
      the FAB subtype, the Bournemouth score, or to peripheral cytopenias. However, Fas
      expression intensity on CD34+ cells negatively correlated to the BM blasts number
      (Spearman, P = 0.01) suggesting that leukemic blasts cells lose Fas antigen
      expression with progression of myelodysplasia. Using both proliferation assays in
      liquid cultures and clonogenic progenitor assays in the presence of an agonist
      anti-Fas MoAb (CH11), we showed that the Fas protein was functional in some
      patients. Dose-dependent inhibition of DNA synthesis was observed in three out of
      seven patients studied. CFU-GM and BFU-E colonies suppression in some patients
      suggested that Fas can induce apoptosis in myeloid and erythroid BM progenitors
      of MDS patients. The TUNEL technique on BM smears gave a mean of 12.6% +/- 2.5 of
      bone marrow apoptotic cells in five controls. Patients with MDS had increased
      bone marrow apoptosis (mean 39% +/- 5.7, t-test, P = 0.012). Four out of 15 (26%)
      patients studied with a sensitive radiolabeled DNA ladder technique had typical
      DNA ladders indicative of advanced stages of apoptosis. Massive BM suicide was
      observed in patients with RA (2/2) and RAEB (8/11), whereas apoptosis rates were
      normal or low in patients with RAEB-t (3/3) or secondary AMLs (3/3). Moreover,
      high rates of apoptosis correlated to low Bournemouth score (Spearman, P = 0.01).
      No statistical correlation could be found between Fas expression and apoptosis
      rates. Our results confirm the importance of programmed cell death in MDS. The
      Fas antigen is clearly upregulated on BM cells, but its role in the
      pathophysiology of apoptosis in myelodysplasia is still unclear, indicating that
      many factors positively or negatively interfere with the Fas-mediated pathway of
      apoptosis in vivo and in vitro.

PMID- 9177439
TI  - Expression of B7-2 (CD86) molecules by Reed-Sternberg cells of Hodgkin's disease.
AB  - Ligation of CD28 on T cells with its natural ligands B7-1 (CD80) or B7-2 (CD86)
      provides a major costimulatory signal for T cells and is of potential importance
      for tumor rejection. We previously reported a strong expression of B7-1 on Reed
      Sternberg cells and anaplastic large cell lymphoma cells. We report here our
      findings on B7-2 expression by malignant lymphomas (n = 70). B7-2 was present on
      the neoplastic cells of anaplastic large cell lymphoma in two of three cases
      studied, and on a subpopulation of the malignant cells in one out of four cases
      of follicular lymphoma. B7-2 was not expressed by the neoplastic cells of the
      other non-Hodgkin's lymphomas (n = 32), including T cell-rich B cell lymphoma. In
      contrast, Reed-Sternberg cells in lymph nodes affected by Hodgkin's disease are
      strongly positive for B7-2 (n = 31). Evidence for a functional correlate of this
      expression was obtained by our findings that the combination of anti-B7-1 and
      anti-B7-2 monoclonal antibodies was more effective than each separately in
      blocking allogeneic T cell activation (proliferation and cytokine secretion) by
      Hodgkin's disease-derived cell lines as stimulators. The possible role of B7-1
      and B7-2 expression for the course and symptomatology of Hodgkin's disease is
      discussed.

PMID- 9177440
TI  - Determination of clonality in patients who present with diagnostic dilemmas: a
      laboratory experience and review of the literature.
AB  - Identification of rearrangements in the immunoglobulin heavy chain (IgH), T cell
      receptor (TCR) and other genes assists in the classification of hemopoietic
      disorders. This study reviews a 5 year experience of genotyping as an assessment
      of clonality in a central referral laboratory. Patients were referred for
      assessment if abnormal hemopoietic populations were identified and where standard
      morphology, cytochemistry or immunophenotyping techniques were equivocal and
      unable to establish the diagnosis. Analysis of the antigen receptor genes (IgH
      gene and TCR gamma locus) was performed in 230 patients by either Southern
      blotting or the polymerase chain reaction (PCR). Clonal rearrangements of either
      loci could be demonstrated in 91/230 patients: 56/161 patients analyzed by
      Southern blotting and 48/125 analyzed by polymerase chain reaction. A subgroup of
      patients (n = 88) was analyzed for rearrangement of the immunoglobulin heavy
      chain gene by both techniques. Discordant results were observed in 18 of these
      patients (20%). Analysis of the TCR gamma locus in a separate group demonstrated
      discordant results in eight of 40 patients examined (20%). Clinical outcome could
      be available in 61 patients (median time: 42 months, range 1-68 months): for
      those in whom a rearrangement was detected approximately 80% went on to develop a
      lymphoproliferative disorder although this diagnosis was not able to be made at
      the time the sample was taken. In a subset of patients (n = 14) who presented
      with lymphocytosis after bone marrow transplantation (seven) or solid organ
      transplant (seven), clonal lymphoid populations were demonstrated in
      approximately 50% of cases. The majority of these cases demonstrated the presence
      of Epstein-Barr virus (EBV) by PCR. The clonality of EBV infection was assessed
      by Southern blotting and the significance of these findings are discussed. This
      study explores the differences between Southern blotting and PCR as applied to
      the study of antigen receptor rearrangement studies. We conclude that detecting a
      clonal population is valuable in patients where standard diagnostic techniques
      are equivocal. However, the inability to detect a clonal population should be
      treated with caution and interpreted in light of other investigations.

PMID- 9177441
TI  - No concomitant occurrence of the N-ras and p53 gene mutations in myelodysplastic
      syndromes.
AB  - Mutations of the N-ras oncogene and p53 tumor suppressor gene were simultaneously
      investigated in bone marrow cells from 44 patients with myelodysplastic syndrome
      (MDS) or MDS-derived leukemia by single-strand conformation polymorphism (SSCP)
      analysis followed by direct sequencing. The mutations of the N-ras gene were
      detected only in two cases with MDS-derived leukemia. Three patients with MDS
      derived leukemia and one with refractory anemia with excess of blasts exhibited
      five mutations of the p53 gene. No concomitant mutations of both genes were
      observed in our study, suggesting that alterations of both genes could play an
      important role in the progression of MDS in a non-cooperative manner.

PMID- 9177442
TI  - Differential expression of alternatively spliced pX mRNAs in HTLV-I-infected cell
      lines.
AB  - Human T cell leukemia/lymphotropic virus (HTLV) is a complex 9 kb human
      retrovirus with at least eight alternatively spliced mRNAs expressed from the 3'
      or pX region of the genome. These mRNAs allow for the expression of novel
      proteins from the previously recognized pX open reading frames I and II in
      addition to Tax, Rex and p21rex encoded from orf III and IV. These alternatively
      spliced messages have been detected using reverse-transcriptase polymerase chain
      reaction (RT/PCR) amplification in HTLV-I-transformed T cell lines as well as in
      peripheral blood mononuclear cells (PBMC) from infected patients with and without
      disease. To gain insight into the role of these alternatively spliced mRNAs in
      pathogenesis, we developed a semi-quantitative non-PCR-based RNase protection
      assay to detect and quantitate their presence in HTLV-I-infected cells. Analysis
      of RNA from HTLV-I-infected cells established from patients with adult T cell
      leukemia (ATL) as well as tropical spastic paraparesis/HTLV-I-associated
      myelopathy (TSP/HAM) and both IL-2-dependent and IL-2-independent HTLV-I-infected
      cell lines by RNase protection has confirmed the existence of all of the
      alternatively spliced messages in each cell line analyzed. However, the relative
      quantity of each message was significantly different among these lines suggesting
      that splice site utilization is an important viral regulatory pathway.

PMID- 9177443
TI  - Debate round-table. Appropriate controls for RT-PCR.

PMID- 9177444
TI  - Angioimmunoblastic lymphadenopathy with disseminated human herpesvirus 6
      infection in a patient with acute myeloblastic leukemia.
AB  - A 47-year-old man with acute myeloblastic leukemia (AML) developed
      angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) 4 months after
      induction chemotherapy for AML. During a leukopenic period, the patient suffered
      from pericarditis with massive pericardial effusion in which human herpesvirus 6
      (HHV-6) DNA was detected. Although complete remission of AML was achieved, fever
      persisted and atypical skin rash followed by generalized lymphadenopathy along
      with polyclonal hypergammaglobulinemia appeared. A diagnosis of AILD was made on
      a biopsy specimen of the inguinal lymph node. The patient died of fulminant
      hepatitis and the autopsy showed lymphomatous infiltrates involving the liver,
      bone marrow, lungs, spleen, kidneys and heart. HHV-6 DNA sequences were
      identified in the biopsy specimen of the lymph node and in the involved organ
      tissues. HHV-6 in this patient was variant B. It is known that HHV-6 can be
      reactivated in immunocompromised patients and causes severe complications. This
      unusual clinical course suggests that the immunosuppression associated with AML
      and the additional iatrogenic immunosuppression following cytopenia-inducing
      chemotherapy predisposed the patient to reactivated HHV-6 infection. The
      sequential detection of this virus before and after manifestation of AILD may
      support the evidence that HHV-6 infection could directly or indirectly trigger
      AILD. This is the first time that such a sequence of events has been reported to
      our knowledge. The possibility of HHV-6 infection should be considered when
      unexplained fever and generalized lymphadenopathy are seen in patients with
      leukemia, and administration of antiviral agents should be considered for the
      diagnostic evaluation.

PMID- 9177445
TI  - Increased methotrexate polyglutamylation in acute megakaryocytic leukemia (M7)
      compared to other subtypes of acute myelocytic leukemia.
AB  - Acute myelocytic leukemia (AML) is a malignancy that is intrinsically resistant
      to methotrexate (MTX). AML blasts, when incubated with radiolabeled MTX, form
      lower amounts of long chain polyglutamates compared to acute lymphocytic leukemia
      (ALL) blasts, thus providing an explanation for their lack of responsiveness to
      MTX. Leukemic blasts obtained from two children with acute megakaryocytic
      leukemia (M7 subtype) when incubated with radiolabeled MTX showed increased
      accumulation of total as well as long chain MTX polyglutamates, comparable to
      levels previously demonstrated in another subtype of AML, acute monocytic
      leukemia (M5), as well as in blasts from patients with pre-B ALL. We suggest that
      M7-AML patients with blasts showing increased MTX polyglutamylation might benefit
      from treatment with MTX.

PMID- 9177446
TI  - Normal G-CSF-mobilized CD34+ peripheral blood stem cells in paroxysmal nocturnal
      hemoglobinuria: a perspective for autologous transplantation.

PMID- 9177447
TI  - HLA and Hodgkin's disease: reply to Taylor and Gokhale.

PMID- 9177448
TI  - Unusual cytogenetic evolution in CML treated with interferon-alpha.

PMID- 9177449
TI  - Enhancement of mdr1 gene expression by transforming growth factor-beta1 in the
      new adriamycin-resistant human leukemia cell line ME-F2/ADM.

PMID- 9177450
TI  - Long-term feeding of field bean protein containing protease inhibitors suppresses
      virus-induced mammary tumors in mice.
AB  - Protease inhibitors (PIs) of synthetic, bacterial or soybean origin have been
      shown to suppress carcinogen or radiation-induced rat mammary carcinogenesis. We
      report, for the first time, the effect of year-long feeding of Field bean meal, a
      rich source of PIs with a 24% protein content, at different protein levels in the
      diet, on mouse mammary tumor virus (MMTV)-induced mammary tumorigenesis in
      C3H/Jax mice. Weanling female mice were randomized and divided into groups and
      fed chow or chow with 2%, 4%, 8% FB protein (FBP) or autoclaved 2% FBP (AFBP)
      until 49 weeks and the incidence of mammary tumors was recorded until 58 weeks
      when they were sacrificed. Mice fed 2% FBP showed significant (P < 0.001)
      reduction (68%) in tumor incidence and delay (P < 0.02) in tumor appearance
      compared to controls. This suppressive effect on mammary tumorigenesis increased
      with increased FBP intake with values of tumor suppression being 75% and 81% in
      mice groups fed 4% and 8% FBP, respectively. Incidentally, the tumors appeared
      earlier (P < 0.05) in the 8% FBP-treated mice compared to other groups. Moreover,
      this suppressive effect on mammary tumorigenesis was related to the PI activity
      of the FB meal, since mice fed 2% AFBP showed no reduction in tumor incidence.
      Heat treatment, which had destroyed the PI activity, apparently did not affect
      other chemopreventive agents known to be present in plant material. This
      possibility is supported by our observation that prolonged feeding of 2% FBP or
      2% AFBP increased the liver glutathione content of mice, suggesting the presence
      of a highly heat-stable factor, other than PIs, in the FBP, which brought about
      this elevation. Further, while 2% or 4% FBP- and 2% AFBP- treated mice showed no
      adverse growth effects, only the 8% FBP-fed group showed a significant lower
      growth curve compared to control mice, with some of them showing pancreatic
      lesions.

PMID- 9177451
TI  - Extracellular matrices expression in invasion area of adenoid cystic carcinoma of
      salivary glands.
AB  - Adenoid cystic carcinoma (ACC) is a salivary malignant tumor with poor long-term
      prognosis, that is known to have predilection for invasion of the adjacent stroma
      and neural tissues. This carcinoma has shown a high incidence of recurrence and
      distal metastasis. Invasive carcinomas have been associated with the
      distributions of extracellular matrices (ECM). Cell proliferation as a marker of
      tumor growth has been related to poor prognosis in oral carcinomas.
      Immunohistochemical analysis of 15 cases of ACC was done using antibodies to
      laminin, type IV collagen, fibronectin, tenascin and anti-proliferating nuclear
      antigen (PCNA). Laminin and type IV collagen were totally or partially absent in
      the ACC invasive areas. Tenascin was expressed in the stroma and cytoplasm and
      was associated with tumor cell proliferation. It can be concluded that basement
      membrane represents a barrier that is lost during cell invasion and tenascin may
      be involved in the detachment of cancer cells, increasing the invasive potential
      of ACC.

PMID- 9177452
TI  - A novel methodological approach to study the level of specific protein and gene
      expression in aberrant crypt foci putative preneoplastic colonic lesions by
      Western blotting and RT-PCR.
AB  - Aberrant crypt foci (ACF) represent microscopic preneoplastic lesions, present in
      the carcinogen-treated rodent colons. The cellular and molecular changes
      occurring within these lesions may provide important clues to the sequence of
      events leading to advanced preneoplastic or neoplastic lesions. The main
      objective of this investigation was to determine whether intact mRNA and protein
      can be isolated from fixed tissue and studied. A pure population of ACF was
      harvested from colonic tissue that had been preserved in 70% ethanol or 10%
      buffered formalin, by using a dissecting microscope and plucking the ACF out
      using fine forceps. The standard procedure of isolating RNA was performed
      successfully on ACF and normal tissue preserved in 70% ethanol. The expression of
      a housekeeping gene, beta-actin was demonstrated. Analysis of ethanol-preserved
      ACF for phosphorylated proteins was carried out by immunoblotting. The present
      study demonstrated that ACF are easily harvested from fixed tissues and that
      intact RNA and protein can be isolated from ACF or normal epithelium which can be
      used in techniques such as immunoblotting and RT-PCR.

PMID- 9177453
TI  - TNF-alpha stimulates the biosynthesis of complement C3 and factor B by human
      umbilical cord vein endothelial cells.
AB  - The human umbilical cord vein (HUVEC) endothelial cells synthesize and secrete
      complement components. We analyzed the regulation of biosynthesis of the third
      component of complement (C3) and factor B (Bf) by cytokines in endothelial cells.
      Production of C3 increased after stimulation with TNF-alpha or IL-1beta and that
      of Bf with TNF-alpha, TNF-beta and IFN-gamma. TNF-alpha was the most effective in
      stimulating the secretion of C3 and Bf or the expression of mRNA of C3 or Bf.
      Preincubation with TNF-alpha for at least 36 or 24 h was needed for the
      stimulation, respectively. TNF-alpha, together with IFN-gamma had synergistic
      effects and the release of C3 or Bf increased to about 40- and 26-fold higher
      than those in control cells after incubation with both cytokines.

PMID- 9177454
TI  - Pancreas cancer, tobacco smoking and consumption of alcoholic beverages: a case
      control study.
AB  - A population-based case-control study investigated pancreas cancer in relation to
      consumption of alcoholic beverages, tobacco smoking and pancreatitis, utilizing
      historical proxy data for 662 decedent Finnish pancreas cancer cases and 1770
      cancer controls. Tobacco smoking increased the risk, with an attributable case
      fraction of 0.27. The data are consistent with a joint effect of early and late
      stage carcinogens in tobacco smoke. Consumption of distilled beverages did not
      increase risk, but heavy drinking of wine or beer did. History of pancreatitis
      was a strong risk factor.

PMID- 9177455
TI  - Lack of a point mutation of human DNA topoisomerase II in multidrug-resistant
      anaplastic thyroid carcinoma cell lines.
AB  - DNA topoisomerases are major defined targets for a large variety of clinically
      important anticancer agents, including etoposide, adriamycin, and mitoxantrone.
      Mutations at amino acids 439, 450 and 803 of DNA topoisomerase II were examined
      in multiple anticancer drug-resistant anaplastic thyroid carcinomas (ten cell
      lines and three cancerous tissues) by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and subsequent DNA sequencing. No mutation was found in these
      cell lines and tissues, but mdr1, mrp and/or lrp mRNA were expressed to a varying
      degree, and there was no significant difference in DNA topoisomerase IIalpha
      content among the cell lines and tissues as evaluated by Western blotting. Our
      experimental data indicate that overexpression of multidrug resistance-related
      mRNA is sufficient to confer drug resistance.

PMID- 9177456
TI  - Tamoxifen inhibits prolactin signal transduction in ER - NOG-8 mammary epithelial
      cells.
AB  - Tamoxifen (TAM), an antiestrogen, also acts as an antilactogen in mammary cells.
      In the present study we analyze the effect of TAM on the signal transduction
      pathway for prolactin (Prl). TAM bound specifically to NOG-8, an estrogen
      receptor-negative mammary cell line. Within 5 min of Prl treatment, raf-1, MEK
      and MAP kinase were induced 2-3-fold over the control level. TAM completely
      inhibited this Prl-induced activation of kinases as well as Prl binding and cell
      growth. These results indicate the potential role of TAM as an antilactogen in
      Prl responsive systems.

PMID- 9177457
TI  - Post-initiation inhibitory effects of green tea catechins on 7,12
      dimethylbenz[a]anthracene-induced mammary gland carcinogenesis in female Sprague
      Dawley rats.
AB  - The dose-dependence of green tea catechin (GTC) effects on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced mammary gland carcinogenesis were
      investigated in female Sprague-Dawley rats. Groups of 20 6-week-old rats were
      treated with dietary 1, 0.1 or 0.01% GTC for 2 weeks and then basal diet alone
      for 35 weeks. At the end of week 1, they received a 25 mg/kg body weight
      intragastric dose of DMBA. Further groups of 20 7-week-old rats each were given
      an intragastric dose of 25 mg/kg body weight DMBA, and starting 1 week after DMBA
      treatment they were placed on diet containing 1, 0.1 or 0.01% GTC or basal diet
      alone for 35 weeks. Control rats were given 1% GTC or basal diet alone. The final
      incidences and multiplicities of mammary tumors were not significantly different
      between the groups treated with GTC at the same time as DMBA, compared to the
      DMBA alone control group. On the other hand, the final multiplicities of mammary
      tumors in groups treated with 1% GTC (P < 0.05) or 0.01% GTC (P < 0.01), but not
      0.1% GTC, after DMBA treatment were significantly decreased as compared to the
      control value. These results indicate that whereas GTC may inhibit mammary
      carcinogenesis in the post-initiation stage, the effect is weak and not dose
      dependent.

PMID- 9177458
TI  - Expression of Fas-estrogen receptor fusion protein induces cell death in
      pancreatic cancer cell lines.
AB  - Recently, a novel system to induce apoptosis was reported. Fusion protein between
      Fas and the ligand-binding domain of the estrogen receptor (MfasER) could cause
      apoptotic cell death in an estrogen-dependent manner on murine fibrosarcoma L929
      cells and human cervical carcinoma HeLa cells [1]. To investigate the application
      of this system to the gene therapy of pancreatic cancer, we introduced MfasER
      cDNA to six cell lines. Transiently expressed MfasER could cause cell death in
      all the cell lines tested. Furthermore, stably MfasER-expressing cells showed DNA
      fragmentation as early as 2 h and completely died in 48 h in the presence of
      estrogen. Combined with effective methods to introduce genes to pancreatic cancer
      selectively, MfasER would be a good tool for the gene therapy of pancreatic
      cancer in the future.

PMID- 9177459
TI  - Effects of dehydroepiandrosterone and calorie restriction on the Bcl-2/Bax
      mediated apoptotic pathway in p53-deficient mice.
AB  - Modulation of apoptosis through altered expression of Bcl-2 and/or Bax may be a
      mechanism by which dehydroepiandrosterone (DHEA) administration and calorie
      restriction (CR) exert their chemopreventive effects in p53-deficient (p53-/-)
      mice. Using immunohistochemical detection we found that treatment with both DHEA
      and CR resulted in decreased expression of the PCNA proliferation marker in the
      thymus. In addition, treatment with DHEA also increased the rate of apoptosis in
      the thymus, resulting in marked thymic atrophy. Thus, both DHEA and CR appear to
      shift cell number homeostasis by favoring apoptosis. To further understand the
      molecular mechanisms by which DHEA and CR exert their effects, we examined two
      components of the apoptotic pathway, Bcl-2 and Bax. We found that p53-/- mice
      have much higher levels of Bcl-2 mRNA in the thymus than wild-type (p53+/+) mice.
      Treatment of p53-/- animals with DHEA resulted in decreased Bcl-2 but not Bax
      mRNA levels in the thymus. In contrast, CR did not change either Bcl-2 or Bax
      mRNA expression. The present study provides molecular evidence that DHEA and CR
      may modulate tumorigenesis through alterations in the apoptotic and/or
      proliferative pathways.

PMID- 9177460
TI  - An inverse correlation between expression of NCAM-A and the matrix
      metalloproteinases gelatinase-A and gelatinase-B in human glioma cells in vitro.
AB  - Matrix metalloproteinases (MMPs) are an homologous family of proteolytic enzymes
      capable of degrading components of the extracellular matrix (ECM) and thereby
      facilitating the invasion of tumour cells into normal tissues. The neural cell
      adhesion molecules (NCAMs) of neuronal and glial cells provide a Ca2+-independent
      mechanism for cell-cell and cell-ECM adhesion. NCAMs are downregulated to promote
      cell disaggregation during cell migration in the developing nervous system
      whereas MMPs facilitate migration. Recent studies have shown downregulation of
      MMP secretion in rat glioma cells transfected with an NCAM cDNA, implying an
      inverse correlation between NCAM and MMP expression. The purpose of this study
      was to establish whether such a correlation could be demonstrated in a panel of
      nine human glioma cell-lines, one metastatic carcinoma and one foetal astrocyte
      derived cell line. The secretion of two MMPs, 72 kDa gelatinase (MMP-2 or
      gelatinase-A) and 92 kDa gelatinase (MMP-9 or gelatinase-B), was investigated
      using SDS-PAGE zymography; NCAM-A was assayed by an immunochemiluminescent assay
      following SDS-PAGE of whole-cell extracts. An inverse correlation was found
      between the expression of NCAM-A and that of both MMPs studied although the
      patterns of expression showed no obvious correlation with histological type or
      grade of the parent tumours. Our results suggest that downregulation of NCAM-A
      may contribute to tumour invasiveness by promoting both cell disaggregation and
      protease secretion.

PMID- 9177461
TI  - Nocturnal 5-fluorouracil infusion to patients with breast cancer prior to
      surgery: appearance of 5-fluorouracil-induced AgNORs aggregation (FAA).
AB  - Between 1994 and 1995, 1 day nocturnal infusion of 5-fluorouracil (5-FU) was
      performed prior to surgery in 13 primary breast cancer patients; 300 mg/m2 of 5
      FU was infused constantly from 2100 h to 0700 h via peripheral vein with a
      volumetric pump. 5-FU concentration in tissues was measured within surgical
      specimens by HPLC. The concentrations of 5-FU in tumor tissues ranged from 6 to
      49 ng/g (average +/- SEM 25.0 +/- 4.1 ng/g), while in normal breast tissues and
      adipose tissues 5-FU was below the detection limit (<3 ng/g). The 5-FU
      concentration was lower in estrogen-receptor-positive tumors (14.4 +/- 4.5 ng/g)
      than in estrogen-receptor-negative tumors (31.8 +/- 5.0 ng/g). Typical FAA was
      observed in the tumor tissues of three patients. In these three cases, AgNORs
      were aggregated to one large spheroidal figure in more than 39% of tumor cells.
      Appearance of FAA could not be predicted by other clinical features. Nocturnal 5
      FU infusion caused FAA changes in certain types of primary breast cancer.

PMID- 9177462
TI  - Anti-tumor effectiveness of electrochemotherapy with bleomycin is increased by
      TNF-alpha on SA-1 tumors in mice.
AB  - With the aim to increase anti-tumor effectiveness of electrochemotherapy,
      adjuvant immunotherapy with tumor necrosis factor-alpha (TNF-alpha) was tested on
      tumors in mice. Increased anti-tumor effectiveness on SA-1 tumors was observed
      after combining TNF-alpha, injected either intratumorally or peritumorally, with
      electrochemotherapy using suboptimal dose of bleomycin (BLM). The increased anti
      tumor effectiveness was neither the result of potentiated anti-tumor
      effectiveness of TNF-alpha due to exposure of tumors to electric pulses, nor due
      to interaction with BLM. Therefore, the effect of adjuvant TNF-alpha treatment
      might be immunomodulatory, augmenting the anti-tumor activity of
      electrochemotherapy, and possibly adding a systemic component to the localized
      electrochemotherapy treatment.

PMID- 9177463
TI  - Autoantibodies to p53 in ovarian cancer patients and healthy women: a comparison
      between whole p53 protein and 18-mer peptides for screening purposes.
AB  - Autoantibodies against complete p53 protein and 18-mer peptides of p53 in ovarian
      cancer patients and healthy women were examined. Sera from 9% (4/46) of ovarian
      cancer patients but none (0/51) of healthy women recognized complete p53 protein.
      The antibodies were mainly of the IgG1 isotype. Two patients had also IgG2
      antibodies. Sera from 28% (13/46) of cancer patients and 21% (11/52) of healthy
      women contained either IgM, or IgM plus IgG2 antibodies against 18-mer p53
      peptides. Screening against complete p53 protein instead of peptides seems
      necessary for identifying patients with tumor-related antibodies. IgG2 antibodies
      against p53 suggest p53-specific CD4+ T helper 1 cell activity in some of the
      ovarian cancer patients.

PMID- 9177464
TI  - Synergistic effect between doxorubicin and a low dose of all-trans-retinoic acid
      in MCF-7 breast cancer cell line.
AB  - The effect of doxorubicin (DOX) used in combination with a low dose (10(-7) M) of
      all-trans-retinoic acid (tRA) was tested on MCF-7 breast carcinoma cell line.
      Both drugs are able to inhibit cell proliferation in these cells in a dose
      dependent way. The combined treatment with DOX and tRA was more effective in
      inhibiting cell growth than each of the two compounds alone. This was evidenced
      in the following experimental conditions: pre-treatments with tRA, for 72 h or 18
      h, before DOX incubation; post-treatment with tRA for 18 h after DOX incubation.
      A consistent synergism was reached by 72 h pre-treatment with tRA and also with
      brief pre- and post-treatments, but only if tRA was also present during DOX
      incubation (co-treatments). The mechanisms involved in this interaction between
      chemotherapeutics and differentiating agents are as yet unclear and should be
      evaluated further.

PMID- 9177465
TI  - Differential effect of intestinal neuropeptides on invasion and migration of
      colon carcinoma cells in vitro.
AB  - We investigated the effect of neuropeptides, which are vasoactive intestinal
      polypeptide (VIP), substance P, (SP), neuropeptide Y (NPY), neurokinin A (NKA),
      somatostatin (SOM), calcitonin gene-related peptide (CGRP), and leucine
      enkephalin (L-ENK), on the invasion of murine Colon 26-L5 adenocarcinoma cells
      through a reconstituted basement membrane (Matrigel) using a Transwell cell
      culture chamber assay. VIP, SP, NPY, and L-ENK reduced invasive potential of
      tumor cells in a concentration-dependent manner, whereas SOM, CGRP, and NKA had
      no effect. Especially, VIP showed the most effective in inhibiting tumor
      invasion, and achieved 50% reduction at 10(-6) M. A similar effect by VIP was
      also observed in cell migration to fibronectin. VIP had no effect on the growth
      of tumor cells at the concentrations ranging from 10(-10) to 10(-6) M. The
      suppressed ability of the tumor cell motility by VIP (10(-6) M) was practically
      recovered by co-treatment with 2',5'-dideoxyadenosine, an adenylate cyclase
      inhibitor. These results indicate that VIP, among the neuropeptides used, could
      inhibit Matrigel invasion of Colon 26-L5 carcinoma cells through partial
      suppression of their motility, and the reduction was associated with an
      intracellular cAMP-mediated pathway.

PMID- 9177466
TI  - Markedly induced asialoGM1+CD8+ T cell production and enhancement of
      antimetastatic activity by interferon beta with folic or folinic acid.
AB  - Either folic or folinic acid enhanced the antimetastatic activity of recombinant
      murine interferon beta (rMulFN beta) toward highly metastatic colon carcinoma 26
      (Co 26Lu). Folinic acid administered with rMuIFN beta markedly increased
      asialoGM1+CD4+ and asialoGM1+CD8+ T cell production in the peritoneal cavity but
      not in the thymus and spleen. Peritoneal cells expressed killing activity toward
      Co 26Lu cells in vitro. In athymic nude mice, the above combination produced many
      asialoGM1+CD4+ and few asialoGM1+CD8+ T cells in the peritoneal cavity, but did
      not decrease lung metastatic colonies. AsialoGM1+CD4+ T cells would thus appear
      to have no or only very weak killing activity toward these tumor cells. The
      antimetastatic activity of folinic acid with rMuIFN beta was significantly
      decreased with anti-asialoGM1 and anti-CD8 antibodies. Inactivated CD8+ and
      asialoGM1+ cells cease to have killing activity toward Co 26Lu cells as shown by
      Winn's assay. AsialoGM1+CD8+ cell production was markedly induced in the
      peritoneal cavity by treatment with rMuIFN beta and folinic acid. AsialoGM1+CD8+
      T cells may be inhibiting lung metastasis of Co 26Lu. Folinic acid and interferon
      are used in combination therapy with 5-fluorouracil for biochemical modulation.
      Folinic acid with interferon, as adjuvant therapy, may promote the induction of
      CD8+ T cell production with consequent prevention of metastasis.

PMID- 9177467
TI  - Role of perforin, granzymes and the proliferative state of the target cells in
      apoptosis and necrosis mediated by bispecific-antibody-activated cytotoxic T
      cells.
AB  - Bispecific monoclonal antibodies (bi-mAb), directed against a tumor-associated
      antigen and the CD3 or CD28 antigen on T lymphocytes, induce activation of
      resting T lymphocytes and target-specific tumor cell lysis. We now show that both
      necrosis and apoptosis contribute to T-cell-mediated tumor cell destruction. Even
      though T cells up-regulate FAS/APO-1 expression upon bi-mAb stimulation, FAS/APO
      1-mediated apoptosis does not contribute to bi-mAb-mediated destruction of
      Hodgkin's cells. CD8+ lymphocytes were the most potent effectors of bi-mAb
      mediated cytotoxicity and had the highest levels of mRNA coding for perforin and
      granzyme A and B. Ca2+-complexing agents, which abrogate perforin activity, led
      to decreased levels of necrosis, while inhibition of granzyme activity in
      effector or target cells had a similar effect on apoptosis. Granzyme-mediated
      apoptosis critically dependent on the proliferative state of the target cells,
      while perforin-induced necrosis was not cell-cycle-dependent. Our results
      underline the importance of the expression levels of perforin and granzymes in
      the effector T cells and of the proliferative state of the target cells in bi-mAb
      mediated apoptosis and necrosis of tumor cells.

PMID- 9177468
TI  - Prevention of superantigen-induced tolerance in vivo by interleukin-2 treatment.
AB  - Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both
      CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR)
      variable-region beta (V beta) chain. T cells respond with profound cytokine
      production and induction of cytotoxicity. Repeated injections, however, cause
      deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency
      of SEA-responsive cells TCR-V beta11+ as well as reduced cytokine levels in serum
      upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA
      responsive CD4+ and CD8+ cells from SEA-induced deletion and/or increase
      expansion of SEA-primed cells as well as preventing downregulation of endogenous
      IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced
      production of important cytokines for the cytotoxic function of T cells, tumour
      necrosis factor alpha, interferon gamma and IL-6, on a cellular level. These
      studies show that continuous stimulation with IL-2 in vivo could be useful for
      superantigen-based immunotherapy by induction of excessive T cell activation and
      by prevention of the development of T cell deletion and anergy.

PMID- 9177469
TI  - Establishment of internal-image anti-idiotype monoclonal antibodies to a human
      antibody to lung cancer.
AB  - Internal-image anti-idiotype antibodies are expected to enhance anticancer
      effector mechanisms in vivo. The objective of this study was to establish
      hybridomas producing anti-idiotype monoclonal antibodies against a human
      monoclonal antibody (hmAb) 4G12 that reacts strongly with lung squamous cell
      carcinomas. BALB/c female mice 6 weeks old were immunized with 4G12. Splenocytes
      were hybridized with P3U1 cells and hybrid cells secreting anti-4G12 hmAb were
      cloned. Two clones reacted with 4G12 hmAb but not with 3H12 IgM hmAb, human IgM,
      human serum or fetal calf serum. These two Ab2 antibodies (IgG1 kappa) 2B12 and
      2H1 demonstrated 91.5% and 90.3% inhibition in their reactivity with
      radiolabelled 4G12 on PC10 cells, indicating that 2B12 and 2H1 antibodies were of
      the Ab2 beta type. In criss-cross inhibition assays, the binding of 2B12 or 2H1
      to 4G12 was not inhibited by 2H1 or 2B12. Thus 2B12 and 2H1 were thought to
      recognize the different epitopes on the antigen-binding sites. Antisera against
      2B12 and 2H1 demonstrated specific reactivity to PC10 cells. The two Ab2 beta
      antibodies, 2B12 and 2H1, express internal images of lung squamous cell carcinoma
      recognized by the 4G12 antibody and may be useful for cancer immunotherapy.

PMID- 9177470
TI  - Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating
      lymphocytes in patients with gynaecological tumours.
AB  - Immunotherapy of gynaecological cancer with tumour-infiltrating lymphocytes (TIL)
      or peripheral blood lymphocytes (PBL) has become a valid treatment modality with
      varying degrees of success in obtaining an antitumour response. TIL consist of
      lymphocytes, mainly T cells and minor populations of natural killer cells or B
      cells. Conventional cytogenetic studies of tumour cells from patients with breast
      and ovarian cancer have shown multiple chromosomal abnormalities including
      chromosomes 7 and 12. This study was designed to analyse the surface further, as
      well as investigate the intracellular, characteristics of TIL by multicolour flow
      cytometry and the cytogenetic features by fluorescence in situ hybridization.
      Tumour cell, peripheral blood and TIL samples from 25 patients (15 ovarian
      tumours, 8 breast cancers, 1 uterine sarcoma, 1 cervical carcinoma) were analysed
      for their phenotype, the expression of major cytokines [interleukin-2 (IL-2), IL
      4 and interferon gamma (IFN gamma)], their proliferation rate, their cytotoxic
      ability and for the presence of numerical aberrations of chromosomes 7 and 12.
      All the tumour cells showed a high frequency of numerical aberration in
      chromosomes 7 and 12, especially trisomies or tetrasomies and combined
      aberrations. Trisomies of both chromosomes also occured at a low percentage in
      TIL and PBL. The phenotyping of TIL and PBL revealed rather similar subsets of
      lymphocytes. In both, T cells were the major population, with TIL containing a
      slightly increased CD4/CD8 ratio. The cytokine pattern showed a predominance of
      IL-4 production in TIL and of IFN gamma in PBL, indicating that, in TIL, cellular
      immunity is downregulated, whereas in PBL the cytotoxic immune response
      predominates. This is in accordance with the cytotoxic ability of TIL, which is
      weakened in comparison to PBL. Cellular characteristics revealed some
      disadvantages in the use of TIL for cancer treatment, explaining ineffective
      clinical results. The search for specific antitumour lymphocytes requires
      carefully designed experiments in order to define effective anticancer cells and
      thereby improve immunologically mediated tumour therapy.

PMID- 9177471
TI  - 1alpha,25-dihydroxyvitamin D3 activates T cells of tumor bearers through protein
      phosphatase 2A.
AB  - The sterol 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit T cell
      activation as well as restore the functional competence of suppressed T cells,
      The present studies determined whether 1,25(OH)2D3 had a differential effect on
      the activation of normal T cells or of suppressed T cells from mice bearing Lewis
      lung carcinoma tumors. Normal spleen cell proliferation in response to
      immobilized anti-CD3 was unaffected by the lower doses of 0.1-10 nM 1,25(OH)2D3,
      and was inhibited by the higher dose of 100 nM 1,25(OH)2D3. In contrast,
      1,25(OH)2D3 increased proliferation and interferon gamma secretion by T cells of
      tumor bearers in response to stimulation through T cell receptor/CD3. Assessment
      of mechanisms associated with the 1,25(OH)2D3 stimulation of tumor-bearer T cells
      implicated protein phosphatase 2A (PP-2A). First, PP-2A activity of spleen cells
      from tumor bearers was reduced compared to that of normal spleen cells but was
      increased by 1,25(OH)2D3. Second, 1,25(OH)2D3 stimulation of tumor-bearer T cell
      proliferation was dependent on this PP-2A activity as it was blocked by doses of
      okadaic acid that selectively inhibit PP-2A. These results suggest that
      1,25(OH)2D3 preferentially enhances the responsiveness of immunosuppressed T
      cells from tumor bearers to TCR/CD3 stimulation by restoring PP-2A activity.

PMID- 9177472
TI  - Rapid elimination of mouse/human chimeric monoclonal antibodies in nude mice.
AB  - At our laboratory we are currently evaluating the suitability of mouse/human
      chimeric monoclonal antibodies (cmAb) for use in radioimmunotherapy of patients
      with head and neck squamous cell carcinoma (HNSCC). We have developed cmAb
      containing the human constant IgG1 domain and the variable domains of murine mAb
      (mmAb) E48 and U36 respectively. We considered the tumour-bearing nude mouse to
      be a well-validated model for a first testing of the targeting capabilities of
      these cmAb in comparison with the mmAb. Therefore, 3 microg cmAb E48 (labelled
      with (125)I) and 3 microg mmAb E48 (labelled with (131)I) were simultaneously
      injected into HNSCC-bearing nude mice and, at various assay times, mAb uptake in
      blood and other tissues was assessed. Remarkably, while in roughly 50% of the
      animals the biodistribution of the conjugates was similar, in the other animals
      cmAb E48 showed a much higher blood clearance than mmAb E48. This resulted in a
      lower tumour uptake of cmAb E48 in comparison with mmAb E48. To determine whether
      this phenomenon was related to mAb E48 or to the animal model, other cmAb-mmAb
      combinations were evaluated in the same way: cmAbs SF-25, 17-1A and U36 (all
      IgG1) were tested and all showed a rapid elimination in about 50% of the animals.
      Besides a decrease in blood concentration, an increase of cmAb levels in liver
      and spleen was observed within 24 h after injection. Isotype-specific enzyme
      linked immunosorbent assays showed that mice that demonstrated a rapid
      elimination of cmAb from the blood had much lower endogenous IgGI, IgG2b and IgG3
      titres than mice showing normal clearance. IgG2a levels were low in all mice.
      Biodistribution experiments with 3 microg chimeric 17-1A isoforms showed high
      blood clearance in a proportion of the mice for IgG1, IgG3 and IgG4, but not for
      IgG2. Increase of the cmAb dose to 100 microg resulted in a similar cmAb and mmAb
      biodistribution in all mice. Moreover, the biodistribution of the F(ab')2
      fragment of an IgG1 cmAb was similar for all mice in contrast to that of
      coinjected whole IgG. On the basis of these results it can be hypothesized that,
      in mice with low endogenous IgG titres, cmAb with specific isotypes are rapidly
      removed from the blood (and ultimately from the body) by mediation of Fc-binding
      receptors. Apparently, in mice with high endogenous IgG titres or in mice
      receiving a high cmAb dose, these receptors are saturated. Furthermore, the rapid
      elimination of cmAb from nude mice, which may occur after injection at a low
      dose, is a phenomenon related to the nude mouse model.

PMID- 9177473
TI  - p53 serum antibodies as prognostic indicator in head and neck cancer.
AB  - p53 antibodies are a new serological parameter of unknown potential in patients
      with malignancies. Their occurrence has been described in various types of cancer
      patients. The mechanism underlying the immunization process is still unclear. We
      investigated the incidence of p53 serum antibodies in 143 head and neck cancer
      patients with an enzyme-linked immunosorbent assay. The posttherapy course of two
      matched study groups (n = 38 each), one p53-antibody-seropositive and one p53
      antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck
      cancer patients (27.3%) were seropositive for p53 antibodies. During the follow
      up, the p53-antibody-seropositive patients accounted for more local tumor
      recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n
      = 5) than did seronegative patients, and second primary tumors (n = 9 versus n =
      0) occurred exclusively in seropositive patients. In total, therapy failures
      (recurrences, tumor-related deaths, second primaries) were observed in 17/38
      cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in
      the p53-antibody-seronegative group. These results, after a follow-up of 2 years,
      seem to indicate a prognostic value of p53 serum antibodies for therapy failure
      in patients with head and neck cancer.

PMID- 9177474
TI  - Interleukin-2 secretion by KHT sarcoma cells leads to loss of their vaccine
      potential.
AB  - We have investigated the effect of interleukin-2 (IL-2) secretion by KHT sarcoma
      cells upon their vaccine potential in syngeneic C3Hf/He mice. Parental KHT tumor
      cells were transfected with the plasmid pBCMG-neo-mIL-2 to obtain a transfectant
      KHT-2-3-7 that secreted 20 units IL-2. KHT-2-3-7 cells elicited protective
      immunity in only 10% of the immunized mice, compared with 40% of mice immunized
      with irradiated parental KHT tumor colls. To minimize the contribution of
      potential antigenic differences between the KHT-2-3-7 transfectant and parental
      KHT cells, a clone of KHT cells (KHT-C21) was isolated and used in subsequent
      experiments. A number of transfectants secreting various amounts of IL-2, ranging
      from 2 units to 200 units, were obtained following transfection of KHT-C21 cells
      with plasmid pBCMG-neo-mIL-2. Two of the transfectants, C21-13-4 and C21-1, each
      secreting 200 units IL-2, elicited protective immunity in a significantly lower
      fraction of mice than did irradiated KHT-C21 parental tumor cells (P<0.01). Two
      other transfectants C21-10 and C21-11, secreting 2 and 23 units IL-2
      respectively, also showed lower vaccine potential compared with the parental KHT
      C21 clone (P<0.05). To minimize further any role for potential antigenic or other
      molecular differences between the individual transfectants and the clonal KHT-C21
      parental cells in lowering their vaccine efficacy, mice were immunized with a
      mixture of five transfectants, and the results again showed significantly lower
      vaccine efficacy of the mixture compared with the irradiated parental C21 cells
      (P<0.01). In view of published studies showing enhanced or unchanged efficacy of
      IL-2-secreting tumor cell vaccines, our observation of the lower vaccine
      potential of IL-2-transduced tumor cells indicates that the vaccine efficacy of
      IL-2-secreting tumor cells depends on the individual tumor. Such
      variability/unpredictability would hamper the clinical use of IL-2-secreting
      tumor cells as vaccines.

PMID- 9177475
TI  - The complete amino acid sequence of human placental oxytocinase.
AB  - The complete amino acid sequence of human placental oxytocinase (placental
      leucine aminopeptidase) has been determined by cDNA cloning and sequencing.
      Oxytocinase is a type II integral membrane protein of 1025 amino acid residues,
      consisting of an acidic intracellular region of 110 amino acids followed by a
      hydrophobic transmembrane segment of 22 residues and 893 extracellular residues
      containing the characteristic Zn2+ coordination sequence element His-Glu-Xaa-Xaa
      His-(18 residues)-Glu found in gluzincins. Two sets of cDNA clones with different
      5'-ends were isolated and suggested to represent different spliced products of
      3.6 kb (mature mRNA) and 12 kb, respectively. Oxytocinase mRNA is present in
      large amounts in placenta, heart and skeletal muscle and in small amounts in
      brain, kidney, liver and pancreas. A conserved sequence element, the GAMEN motif,
      which distinguishes the aminopeptidase family among gluzincins from other
      gluzincins, has been identified.

PMID- 9177476
TI  - A second type of rod opsin cDNA from the common carp (Cyprinus carpio).
AB  - A second type of rhodopsin cDNA from carp (cRh-II) shared 97.2% polynucleotide
      identity with the previously reported cRh-I. The deduced amino acid sequences of
      cRh-I and cRh-II exhibited 98.6% identity. The key difference between these two
      types of cRh is that valine at position 169 of cRh-I was replaced by glutamic
      acid in cRh-II. Southern blot analysis of genomic DNA showed that there were two
      types of cRh gene. These two rod opsin genes were proven to be expressed in carp
      retinas by using RT-PCR with type-specific primers.

PMID- 9177477
TI  - cDNA cloning of two closely related forms of human germ cell nuclear factor
      (GCNF).
AB  - Germ cell nuclear factor (GCNF) was initially described in the mouse as a germ
      cell-specific orphan member of the nuclear receptor superfamily. Two full-length
      cDNAs encoding variants of the human germ cell nuclear factor (GCNF) differing by
      only one amino acid residue have now been isolated from a human testis cDNA
      library and characterised. The encoded proteins show 98.3% and 82.7% amino acid
      identity with mouse and Xenopus GCNF, respectively. Northern blot hybridisation
      revealed the expression of an 8 kb human GCNF mRNA exclusively in the testis. The
      alignment of the GCNF protein sequence with other members of the nuclear hormone
      receptor family suggests an unusual structural organisation of the C-terminal
      portion of the putative ligand-binding domain.

PMID- 9177478
TI  - Cloning and sequencing of the gene encoding the high potential iron-sulfur
      protein (HiPIP) from the purple sulfur bacterium Chromatium vinosum.
AB  - The gene encoding the high potential iron-sulfur protein (HiPIP) of Chromatium
      vinosum strain D (DSM 180T) was cloned from an EcoRI-HindIII digest of genomic
      DNA. A nucleotide sequence of 648 bp length was determined which contained the
      coding region and putative promoter and termination sites. The gene codes for a
      122 residue 12761 Da protein. The C-terminal 85 residues are those of the
      previously biochemically determined sequence, whereas the N-terminal 37 residues
      constitute a leader peptide which shows characteristics of the double arginine
      signal sequences of complex cofactor containing periplasmic proteins.

PMID- 9177479
TI  - Expression cloning and intracellular localization of a human ZF5 homologue.
AB  - We isolated a cDNA encoding a human homologue of ZF5 (hZF5), which has five
      Kruppel-like C2H2 type zinc fingers at carboxyl terminus and the BTB/POZ
      (poxvirus and zinc finger) at the amino terminus, using autoimmune sera from a
      patient with overlap syndrome (dermatomyositis and scleroderma). Sequencing of
      the entire cDNA revealed an open reading frame (ORF) of 1349 bp with a deduced
      protein sequence of 449 amino acid residues and a calculated molecular weight of
      51.3 kDa. The deduced amino acid sequence of hZF5 is highly homologous to mouse
      ZF5 (99.3% identity). Immunofluorescence studies revealed that HA-tagged hZF5
      transiently expressed in COS-7 cells showed the nuclear dot pattern in the
      BTB/POZ domain-dependent manner.

PMID- 9177480
TI  - Coactivation of human alpha1- and alpha2-globin genes in single induced MEL cells
      containing one human alpha-globin locus.
AB  - We developed a reverse-transcription polymerase chain reaction assay, performed
      on single isolated cells, to demonstrate the coexpression of human alpha1- and
      alpha2-globin mRNA in induced mouse erythroleukemic cells containing a single
      human alpha-globin locus. These results indicate that both alpha1 and alpha2
      genes are activated from the same alpha-globin gene locus implying that HS-40
      dependent transcriptional activation is mediated, either by a simultaneous
      interaction of HS-40 with both a alpha1 and alpha2-globin gene promoters, or by a
      dynamic process characterized by alternative, but short-lived, interactions with
      each alpha-globin gene promoter.

PMID- 9177481
TI  - Structure and functional properties of mouse VL30 retrotransposons.

PMID- 9177483
TI  - Gene from tropical Bacillus sphaericus encoding a protease closely related to
      subtilisins from Antarctic bacilli.
AB  - We undertook to identify the protease(s) involved in the in vivo degradation of
      the 100 kDa mosquitocidal toxin (Mtx) from Bacillus sphaericus SSII-1 and
      isolated a B. sphaericus SSII-1 gene flanked upstream by a typical Shine-Dalgarno
      ribosome binding site and downstream by a strong rho-independent transcription
      terminator. The predicted ORF encodes a 432 amino acid protein with significant
      homology throughout its sequence to two subtilisin-like serine proteases from the
      Antarctic psychrophilic (cold-adapted) bacilli, TA39 and TA41. The predicted N
      terminal sequence suggests that the B. sphaericus protease is related to
      sfericase, a partially characterized serine protease from B. sphaericus. Only B.
      sphaericus strains which produce Mtx-degrading protease activity harbour the
      subtilisin-like protease gene, suggesting that this protease may be responsible
      for or contribute to the degradation of Mtx in B. sphaericus SSII-1. A 36-kDa
      protease with Mtx-degrading activity and similar properties to sfericase was also
      purified from sporulated cultures of B. sphaericus SSII-1. Further studies are
      needed to determine the relationship of this protease to sfericase and to the
      predicted product of the subtilisin-like serine protease gene.

PMID- 9177482
TI  - Cloning of two splicing variants of the novel Ras-related GTPase Rab29 which is
      predominantly expressed in kidney.
AB  - cDNA of a novel Ras-related GTP-binding protein was isolated from rat tissue by a
      PCR-based cloning approach, and was designated Rab29 because its deduced amino
      acid sequence (204 aa) is remotely similar to that of members of the Rab family
      (30% identity with Rab1). mRNA of Rab29 was found predominately in kidney.
      Recombinant Rab29 exhibited rapid exchange of bound guanine nucleotides for
      radiolabeled GTP but lacked a detectable intrinsic GTPase activity. A second cDNA
      clone was isolated which contained a 287 bp in-frame insertion with
      characteristics of an intron sequence; this insertion introduces a stop codon
      after arginine 167. The recombinant protein (Rab29delta37) derived from the cDNA
      carrying the insertion was loaded with GTP during biosynthesis, but showed almost
      no exchange of the nucleotide for radiolabeled GTP. Thus, the C-terminus of Rab29
      appears to harbor a structural element which is essential for the nucleotide
      exchange of the protein.

PMID- 9177484
TI  - Cloning and characterization of the gene encoding a mitochondrially localized DNA
      topoisomerase II in Dictyostelium discoideum. Western blot analysis.
AB  - We cloned a gene (topA) encoding DNA topoisomerase II from Dictyostelium
      discoideum nuclear DNA using oligo probes corresponding to the consensus amino
      acid sequences found in the gene in other eukaryotes. The gene encoding a
      predicted polypeptide of 1282 amino acids with M(r) of about 146 kDa, is a single
      copy that is expressed as a polyadenylated 4.5 kb RNA. The predicted amino acid
      sequence shares similarity with those of other eukaryotes with identity between
      32 and 46%. The protein is 260-300 amino acids shorter in the C-terminal region
      and 50-80 longer in the N-terminal region than those of other eukaryotes. In TopA
      of D. discoideum, the N-terminal region with stretches of charged and hydrophilic
      amino acids is predicted to fold into an amphiphilic alpha-helix which is
      characteristic of a mitochondrial targeting signal presequence. Four independent
      polyclonal antibodies against bacterially expressed GST fusion proteins
      containing four portions of the polypeptide detected a single band on Western
      blots at about 135 kDa. Western blots analysis of subcellular fractions revealed
      that this protein is localized in mitochondria. The protein and the mRNA are
      present in growth phase and during development, although levels of both declined
      as development proceeded.

PMID- 9177485
TI  - The regulation of the vanadium chloroperoxidase from Curvularia inaequalis.
AB  - The effects of carbon and nitrogen source on the regulation of the vanadium
      chloroperoxidase secreted by the fungus Curnularia inaequalis were investigated.
      The addition of glucose showed a repressing effect on both the observed messenger
      RNA level and the measured enzyme activities, whereas the addition of glutamate
      as nitrogen source and the addition of both glutamate and glycerol had no effect.
      Addition of vanadate had no effect on the level of mRNA. Eight hundred base pairs
      of the upstream promoter region of vCPO were sequenced and various features of
      interest are highlighted. Closer inspection of the mycelium revealed that once
      secreted, vCPO probably remains tightly associated with the hyphae in two forms,
      one of which may be a proform of the enzyme. A possible cleavage event at the C
      terminus may lower its potential for hyphal association and permit its
      disassociation into the growth medium. A putative role for the vanadium
      chloroperoxidase is put forward.

PMID- 9177486
TI  - Molecular cloning of a cDNA encoding the nucleosome core histone H3 from
      Dictyostelium discoideum by genetic screening in yeast.
AB  - The one-hybrid method for genetic screening in yeast was used to search a
      Dictyostelium discoideum cDNA library for DNA-binding proteins that interact with
      the C-module of the Dictyostelium repetitive element. The C-module was formerly
      shown to contain two high affinity, sequence-specific binding sites for a nuclear
      protein factor of unknown function (CMBF). The bait DNA sequence was bound in
      vivo by a cDNA-encoded protein whose derived amino acid sequence showed high
      homology to nucleosome core histone H3, but not to partially available CMBF
      sequences. The D. discoideum histone H3 homolog is encoded by a single gene and
      shows significant sequence variation at the amino terminus of the protein,
      including a triple-serine insertion not found in any other histone H3.

PMID- 9177487
TI  - Mechanistic studies of the translational elongation cycle in mammalian
      mitochondria.
AB  - Polyclonal antibodies have been prepared against both components of the bovine
      liver mitochondrial translational elongation factor Tu and Ts complex (EF-Tu x
      Ts(mt)). The antibodies against EF-Tu(mt) cross-react somewhat with Escherichia
      coli EF-Tu and wheat germ EF-1alpha. The antibodies against EF-Ts(mt) cross-react
      little, if at all, with E. coli EF-Ts or with EF-Ts from Euglena gracilis
      chloroplasts. These polyclonal antibodies have been used to investigate the
      relative amounts of EF-Tu(mt) and EF-Ts(mt) in bovine liver mitochondria and in
      cultured cells. The results of this analysis suggest that there is a 1:1 ratio of
      EF-Tu(mt) to EF-Ts(mt) in mammalian mitochondria. Intermediate complexes formed
      during the elongation cycle of protein synthesis in bovine liver mitochondria
      have also been investigated. The EF-Tu x Ts(mt) complex is quite resistant to
      dissociation by guanine nucleotides. This complex will, however, dissociate in
      the presence of GTP and Phe-tRNA resulting in the formation of a ternary complex
      comparable to that observed in prokaryotes. Kinetic data suggest that the use of
      the ternary complex in chain elongation increases the rate of Phe-tRNA binding to
      ribosomes, suggesting that it is a true intermediate in the elongation cycle.
      Sucrose gradient analysis indicates that the binding of EF-Tu(mt) to ribosomes
      can be detected in the presence of Phe-tRNA and a non-hydrolyzable analog of GTP.
      These results suggest that, in contrast to previous thinking, the basic features
      of the elongation cycle in mammalian mitochondria are quite similar to those in
      prokaryotes.

PMID- 9177488
TI  - Expression of bovine mitochondrial elongation factor Ts in Escherichia coli and
      characterization of the heterologous complex formed with prokaryotic elongation
      factor Tu.
AB  - When bovine mitochondrial elongation factor Ts (EF-Ts(mt)) is expressed in
      Escherichia coli, it forms a tightly associated complex with E. coli EF-Tu (EF
      Tu(Eco) x Ts(mt)). This complex is active in poly(U)-directed polymerization and
      this activity is inhibited by kirromycin. The EF-Tu(Eco) x Ts(mt) complex does
      not bind guanine nucleotides detectably and is not dissociated to a significant
      extent by either GDP or GTP. A portion of the EF-Tu(Eco) x Ts(mt) complex can be
      dissociated by aa-tRNA in the presence of GTP. The heterologous complex cannot be
      dissociated completely in the presence of either the 8 M urea or 8 M guanidine
      hydrochloride, suggesting that EF-Ts(mt) has an unusually tight interaction with
      E. coli EF-Tu. The EF-Tu(Eco) x Ts(mt) complex can be dissociated by denaturation
      using 2 M guanidine thiocyanate. Free EF-Ts(mt) can then be purified and
      renatured. The refolded EF-Ts(mt) is active in stimulating the activity of
      expressed mitochondrial EF-Tu (EF-Tu(mt)) in poly(U)-directed polymerization.
      Almost all the EF-Ts(mt) molecules appear to refold into a conformation which can
      interact with EF-Tu(mt). Protease mapping of EF-Ts(mt) indicates that the first
      54 residues fold into an independent domain. Analysis of deletion derivatives of
      EF-Ts(mt) indicates that extensive regions of this factor are required for its
      tight interaction with EF-Tu.

PMID- 9177489
TI  - Cloning of poly(3-hydroxybutyrate) depolymerase from a marine bacterium,
      Alcaligenes faecalis AE122, and characterization of its gene product.
AB  - A DNA fragment that carries the gene coding for poly(3-hydroxybutyrate) (PHB)
      depolymerase was cloned from the chromosomal DNA of Alcaligenes faecalis AE122
      isolated from seawater. The open reading frame encoding the precursor of the PHB
      depolymerase was 1905 base pairs (bp) long, corresponding to a protein of 635
      amino acid residues (M(r) = 65,208). The promoter site, which could be recognized
      by Escherichia coli RNA polymerase, was upstream from the gene, and the sequence
      adhering to the ribosome-binding sequence was found in front of the gene. The
      deduced amino acid sequence agreed with the N-terminal amino acid sequence of the
      purified PHB depolymerase from amino acid 28 onwards. Analysis of the deduced
      amino acid sequence revealed the domain structure of the protein; a signal
      peptide of 27 amino acids long was followed by a catalytic domain of about 400
      amino acids, a fibronectin type III module sequence, and a putative substrate
      binding domain. The molecular mass (62,526) of the mature protein deduced from
      the nucleotide sequence was significantly lower than the value (95 kDa) estimated
      on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but coincided well
      with the value (62,426) estimated from matrix-assisted laser desorption
      ionization mass spectra. By comparison of the primary structure with those of
      other PHB depolymerases, the substrate binding domain was found to consist of two
      domains, PHB-specific and poly(3-hydroxyvalerate)-specific ones, connected by a
      linker region. The PHB depolymerase gene was expressed in Escherichia coli under
      the control of the tac promoter. The enzyme expressed in E. coli was purified
      from culture broth and showed the same catalytic properties as the enzyme from A.
      faecalis.

PMID- 9177490
TI  - Influence of the Ward colon tumor on the host response to endotoxin.
AB  - Cachexia and a decreased immune function are negative prognostic factors for
      cancer patients. While the decreased immunity results in a greater susceptibility
      to bacterial infection, the response of the host to the resulting infection is
      not clear. The experiments reported here were designed to evaluate the toxicity
      of endotoxin to rats with a transplantable Ward colon tumor (WCT) and to evaluate
      the mechanism of the observed increase in lethal toxicity. The lethal toxicity of
      endotoxin (lipopolysaccharide, LPS) at 5 mg/kg, i.p. was evaluated in the first
      of two experiments. Rats received LPS and were observed for morbidity and weight
      loss for a period of 11 days. A second experiment was done to evaluate the effect
      of LPS on the plasma nitrate/nitrite concentrations and plasma indicators of host
      tissue dysfunction. LPS was administered as previously described but blood and
      tissues were collected 5 h after LPS administration. LPS resulted in the death of
      1 of 12 nontumor-bearing (NTB) rats and a transient weight loss in the survivors.
      This same dose of LPS, however, resulted in death for 10 of 12 WCT rats with
      tumor burdens less than 4% of body weight. The response of WCT rats 5 h after LPS
      was then compared with that of age-matched NTB rats. Plasma albumin
      concentrations were not affected by LPS in NTB rats but were significantly
      decreased in WCT rats. Peripheral blood gases were not consistently affected by
      LPS in either group. Peripheral blood white cell counts, except monocytes, were
      significantly decreased by LPS in both groups. Monocyte counts in peripheral
      blood were further reduced in WCT rats compared with NTB rats receiving LPS. The
      presence of the WCT significantly enhanced the LPS-associated increase in spleen
      weight. Liver weights were lower in LPS rats but there was no effect of the
      presence of WCT. The LPS-associated increase in plasma nitrate/nitrite
      concentration was enhanced by the WCT. The plasma arginine and citrulline
      concentrations were altered in a manner consistent with an increase in nitric
      oxide synthesis. An increase in plasma ornithine concentration suggests an
      increase in arginine metabolism by arginase. The plasma concentration of alanine
      aminotransferase was significantly elevated when WCT rats received LPS,
      suggesting enhanced hepatic dysfunction. The plasma blood urea nitrogen
      concentration was elevated by LPS to a greater extent in the WCT rats than in the
      NTB controls, indicating increased renal dysfunction. These results demonstrate
      that the Ward colon tumor increases the host lethal response to the endotoxin, a
      toxic product of bacterial infections. The mechanisms of lethality may include an
      increased nitric oxide synthesis in WCT rats and enhanced liver and renal
      toxicity.

PMID- 9177491
TI  - In vitro and in vivo modulation by rhizoxin of non-P-glycoprotein-mediated
      vindesine resistance.
AB  - Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this
      study, we demonstrated that rhizoxin was approximately twice as active in vitro
      against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated
      resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin
      polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited
      markedly by rhizoxin compared with that in H69, in a concentration-dependent
      manner. A drug-accumulation study showed that the intracellular rhizoxin level in
      H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced
      slightly. These results indicate that enhanced inhibition of tubulin
      polymerization rather than increased intracellular drug concentration accounted
      for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice
      with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS,
      in vivo tumor growth was reduced markedly by three intermittent intraperitoneal
      doses of rhizoxin compared with that in mice inoculated with H69. Three weeks
      after the last rhizoxin dose, the relative treated/untreated tumor volumes were
      0.29 for H69, but only 0.06 for H69/VDS, indicating that H69/VDS regrowth was
      minimal even after a 3-week treatment-free period. In conclusion, rhizoxin
      conquers vindesine resistance of a human small-cell lung cancer cell line in
      vitro and in vivo.

PMID- 9177492
TI  - Inhibition of protein kinase C in multidrug-resistant cells by modulators of
      multidrug resistance.
AB  - We have evaluated the protein kinase C (PKC) activity in two series of cultured
      cell lines presenting the multidrug-resistance (MDR) phenotype and in the
      corresponding wild-type cells: the human KB 3.1, KB A1 and KB 8.5 cell lines, and
      the rat C6, C6 0.5 and C6 1V cell lines. We have observed an increase in PKC
      activity in the MDR cell lines of the KB cell lineage, proportional to their
      degree of resistance to doxorubicin. In contrast, the MDR cell lines of the C6
      cell lineage presented no change (C6 0.5) or even decrease (C6 1V) in PKC
      activity; the basal level of PKC activity in C6 cells was, however, 50-fold
      higher than in KB 3.1 cells. We have tested, in these lines, the effect of four
      modulators of MDR: verapamil, cyclosporin A, quinine and S-9788, on doxorubicin
      acytotoxicity and on PKC activity. We observed that cyclosporin A and S-9788,
      which were the most active on MDR reversal, were able to inhibit PKC activity in
      the KB resistant lines as well as in all C6 lines, whereas verapamil and quinine
      had only marginal effects on PKC activity. The distribution of PKC isoenzymes was
      studied by Western blots. The PKC alpha, gamma and delta isoforms were increased
      in the KB resistant lines as compared to wild-type cells, which could account for
      the increase PKC activity we observed. In contrast, PKC alpha and gamma were
      decreased in C6 1V cells, as expected from the results obtained for total PKC
      activity, but we also noticed an important decrease in PKC delta in the C6 0.5
      line. Our results suggest that an increase in PKC activity is not an absolute
      requirement for expression of MDR, provided that the basal level be high enough;
      and that some modulators may act on MDR, not only through direct P-glycoprotein
      interaction, but also through P-glycoprotein phosphorylation or expression. The
      distribution of PKC isoenzymes revealed that the modifications encountered
      between sensitive and resistant cells mainly concerned alpha, gamma and delta
      isoenzymes of PKC.

PMID- 9177493
TI  - p53 gene mutations in soft-tissue sarcomas--correlations with p53
      immunohistochemistry and DNA ploidy.
AB  - The significance of p53 mutations in a group of 67 soft-tissue tumors was
      examined using single-strand conformation polymorphism and direct sequencing
      analysis. Molecular findings were correlated with immunohistochemical detection
      of the p53 protein and DNA ploidy status. Mutations of the p53 gene were detected
      in 13 (19.5%) out of 67 cases of soft-tissue tumors. Only three were localized
      outside the conservative regions of the p53 gene. Six mutations were described
      for the first time in these tumors. Most of the mutations were point mutations in
      exons 5-8 and, in one case, a deletion at the 3'-splice site of exon 5 could be
      demonstrated. There was no significant correlation between the occurrence of p53
      mutations and the histological grade, although a high number of mutations were
      defined in poorly differentiated tumors (grade 3). Molecular finding of a p53
      gene mutation and immunohistochemical detection of p53 expression did not
      correlate, which may be due to the high percentage of nonsense mutations in our
      study (50%). We confirm that only DNA sequencing allows a unique identification
      and differentiation of mutations in the p53 gene. Other factors may be
      responsible for the detection of p53 protein in many cases. Histological grade
      correlated with aneuploidy. The frequency of mutations observed was in accordance
      with values quoted in the literature. Generally, p53 mutations and p53
      overexpression are more likely to represent a late event in the oncogenesis of
      soft-tissue tumors.

PMID- 9177494
TI  - High-intensity focused ultrasound in the treatment of experimental liver tumour.
AB  - This project aimed to determine the adequacy and accuracy of high-intensity
      focused ultrasound (HIFU) for ablating experimental liver tumour, and to assess
      imaging methods for monitoring the therapeutic results. The rabbit liver
      pseudotumour model was established by injection of Freund's complete adjuvant
      into the liver; the animals then received HIFU therapy via laparotomy at the
      focal point of the beam (1.1 MHz, 500 W/cm2, 20 s). The rabbits were sacrificed
      at scheduled times after treatment and liver tumours were examined
      histologically. Sequential imaging of the liver tumour was performed before and
      after HIFU treatment. HIFU accurately destroyed the rabbit liver tumour and
      induced coagulation necrosis 24 h later. Sonographic imaging studies revealed
      that characteristic changes occurred. A hyperechoic mass turned to a hypoechoic
      lesion with no Doppler signal, and a high echogenic rim appeared 24 h after HIFU
      treatment, correlating well with the pathological changes of a sonoablated
      lesion. These results verify that HIFU has the power to ablate liver tumour quite
      adequately and accurately, and that sonography is useful for monitoring
      sonoablated liver tumour.

PMID- 9177495
TI  - Low-dose intravenous ondansetron (8 mg) plus dexamethasone: an effective regimen
      for the control of carboplatin-induced emesis.
AB  - Twenty-nine patients with gynecologic malignancies were treated with a fixed low
      dose of intravenous ondansetron (8 mg) plus dexamethasone (20 mg) in an effort to
      develop an effective and less expensive antiemetic regimen for the control of
      carboplatin-induced emesis. Twenty-six (90%) of the women participating in this
      trial experienced complete control of both acute nausea and vomiting (developing
      within the first 24 h after chemotherapy administration), while 27 (93%) patients
      exhibited either complete or major control (< or = 2 episodes of vomiting, < or =
      5 episodes of retching, minimal interference with eating) of emesis. On the basis
      of our experience in this trial, we conclude that the combination of low dose (8
      mg) intravenous ondansetron plus dexamethasone is a well-tolerated and highly
      cost-effective antiemetic strategy for individuals receiving carboplatin-based
      chemotherapy.

PMID- 9177496
TI  - 6-Day continuous infusion of high-dose ifosfamide with bone marrow growth factors
      in advanced refractory malignancies.
AB  - Ifosfamide is an analogue of cyclophosphamide active in the treatment of numerous
      tumours. Although its use by continuous infusion seems to be responsible for less
      toxicity, differences of efficacy and toxicity, observed according to its doses
      and schedules of administration, still remain debated. The objective of this
      study was to assess the toxicity of high-dose ifosfamide given by continuous
      infusion over 6 days and its therapeutic activity in various advanced tumours.
      Twenty-six patients were treated with 14 g/m2 ifosfamide, an equal dose of MESNA,
      and routine granulocyte- or granulocyte/macrophage-colony-stimulating factor
      during the intercycle. Courses were repeated every 3 weeks until disease
      progression or unacceptable toxicity occurred; 75 cycles were administered. The
      mean number of cycles per patient was 3 (range 1-11). Extrahaematological
      toxicity was manageable in most patients, WHO grade II or more neurological (5
      patients) and renal (5 patients) toxicities occurring in those heavily pretreated
      with platinum compounds and presenting peritoneal disease. WHO grade III or more
      neutropenia occurred in 60% of cycles, while grade III-IV thrombocytopenia and
      anaemia were observed in 19% of them. Three partial responses (germ-cell tumour,
      chondrosarcoma, soft-tissue sarcoma) and one complete response (metastatic
      osteosarcoma) were assessed, all in patients with tumours refractory or resistant
      to standard-dose ifosfamide, which underlines the possibility of circumventing
      the resistance to ifosfamide given in conventional schedules. The present results
      confirm previous reports of changes in the therapeutic index of ifosfamide
      according to its dose and administration schedule.

PMID- 9177497
TI  - DNA Damage from Endogenous Processes, Workshop: 16-17 September 1996, German
      Cancer Research Centre Heidelberg, Germany.

PMID- 9177498
TI  - Thirty-eighth Annual Meeting of the American Society of Hematology.

PMID- 9177499
TI  - Expression of multidrug resistance-associated protein gene in Ewing's sarcoma and
      malignant peripheral neuroectodermal tumor of bone.
AB  - The expression of multidrug resistance-associated protein (MRP) mRNA was examined
      in ten samples of Ewing's sarcoma of bone (ES) and in one nude mice
      transplantable ES and two malignant peripheral neuroectodermal tumor (MPNT) cell
      lines using an RT-PCR assay. MRP mRNA expression was recognized in eight of the
      ten clinical specimen and in all three cell lines. On the other hand, the
      expression of multidrug resistance gene (MDR1) was demonstrated in three of the
      ten clinical samples and all three cell lines. Our results may contribute to
      elucidation of the mechanism of anti-cancer-drug resistance in this tumor.

PMID- 9177500
TI  - Immunohistochemical analysis of p53 protein in transplant recipients with
      Kaposi's sarcoma.
AB  - PURPOSE: Kaposi's sarcoma (KS) is a proliferative process of suspected viral
      aetiology associated with immune deficiency. In transplanted patients, lesions
      regress on discontinuation of immunosuppressive therapy. The purpose of this work
      was to analyse the expression of the p53 oncosuppressor gene product, a
      proliferation regulator overexpressed in both malignant and non-malignant
      conditions, with the aim of better qualifying KS proliferation characteristics.
      METHODS: We analysed p53 expression in a group of transplanted, cyclosporin A
      treated, KS patients by immunohistochemistry, utilizing the DO-7 (with and
      without the antigen retrieval pretreatment), and the PAb 240 monoclonal anti-p53
      antibodies, the latter of which is able to detect a mutated epitope, and
      evaluating staining intensity and localization, whether cytoplasmic or nuclear.
      RESULTS: Seventy five percent of KS lesions from transplanted patients presented
      both nuclear and cytoplasmic positive p53 immunostaining with DO-7 antibody, thus
      demonstrating a presumably functional inactivation; one case also presented
      immunoreactivity with the PAb 240 antibody. CONCLUSIONS: On the basis of the
      results obtained and in the presence of lesion regression upon immunosuppression
      withdrawal, it may be concluded that KS in transplanted patients can be
      considered a non-malignant proliferative process, and that the cytoplasmic
      expression of p53 may stand for a functional inactivation pattern.

PMID- 9177501
TI  - Does sensitization of esophageal mucosal receptors occur during provocative
      testing?

PMID- 9177502
TI  - Band ligation, sclerotherapy, both or ... brains?

PMID- 9177503
TI  - The American College of Gastroenterology Bleeding Registry: preliminary findings.
AB  - OBJECTIVES: The American College of Gastroenterology (ACG) Institute for Clinical
      Research and Education conducted a survey study to assess demographics,
      management strategies, and outcome for patients with gastrointestinal bleeding.
      This pilot project was intended to determine the feasibility of surveying the ACG
      membership about common clinical issues. METHODS: Color-coded survey forms were
      sent to all ACG members and Fellows, with instructions to supply information
      about demographics, presenting symptoms, management, and outcome for bleeding
      patients and procedure-matched controls. Forms returned between June 1 and August
      31, 1995, were tabulated and analyzed for differences between the bleeding group
      and procedure-matched controls. RESULTS: A total of 1235 forms were returned by
      respondents, 60% of whom were in private practice. Patient demographics indicated
      that bleeding patients were significantly older, more likely to be male, and more
      likely to use alcohol, tobacco, and prescription or over-the-counter aspirin or
      nonsteroidal anti-inflammatory drugs and anticoagulants than were controls. Upper
      GI bleeding accounted for 76% of bleeding events, with duodenal and gastric
      ulcers being the source in more than 50% of the upper GI bleeders. Diverticula
      was the most common bleeding source identified in lower GI bleeders. In the
      bleeding group, 78.8% were anemic, with 60.9% having hemoglobin of <10 g/dl; 31%
      presented with orthostatic changes in blood pressure or shock. Most bleeding
      subjects, regardless of source, were hospitalized, 58.2% received blood
      transfusions, and 45.5% received endoscopic therapy. Rebleeding (11.2%), need for
      surgery (7.1%), and fatalities (2.1%) were uncommon. Over-the-counter aspirin and
      nonsteroidal anti-inflammatory drugs were used significantly more often in the
      bleeding population (47.6%) than in controls (19.4%). CONCLUSIONS: The success of
      the GI Bleeding Registry supports the feasibility of surveying ACG members about
      common clinical problems. Data suggest that ACG members manage sick patients with
      severe gastrointestinal bleeding who require hospitalization, transfusions, and
      endoscopic treatment. These preliminary results will serve as an impetus to
      conduct further survey studies of gastrointestinal bleeding and other common
      digestive disease conditions.

PMID- 9177504
TI  - Gastrointestinal uses of botulinum toxin.

PMID- 9177505
TI  - Delayed gastric emptying and postoperative ileus after nongastric abdominal
      surgery: part II.

PMID- 9177506
TI  - Esophageal motility abnormalities in cirrhotic patients before and after
      endoscopic variceal treatment.
AB  - Esophageal motility abnormalities in patients treated endoscopically for variceal
      hemorrhage are rarely studied and usually are not addressed in the clinical
      setting. However, a review of the literature revealed that esophageal varices
      reduce the mean amplitude and increase the mean duration of peristaltic waves but
      have little effect on lower esophageal sphincter function. Transit time is
      delayed and gastroesophageal reflux disease is common in up to 64% of the
      patients. Whereas band ligation appears to have little impact on esophageal
      motility, data are limited and are hampered by lack of standardization, rendering
      conclusions about safety rather premature. Injection sclerotherapy spares the
      lower esophageal sphincter, as well, but it significantly reduces mean amplitude
      contractions, mainly in the lower one-third to one-half of the esophagus. In
      addition, normal peristalsis may be occasionally or completely replaced by
      nonpropagating simultaneous contractions that may result in chest pain and/or
      dysphagia in the absence of stricture. Transient prolongation of acid clearance
      usually resolves within a week, except in patients who have developed stricture.
      Pathogenesis of the abnormal motility remains poorly understood, and treatment
      has been empirical. However, a short course of anti-reflux treatment after each
      therapeutic session is justified, as well as long-term treatment for patients
      with stricture. The choice of treatment for esophageal motility abnormalities is
      less clear and requires future studies.

PMID- 9177507
TI  - Acid infusion does not affect intraesophageal balloon distention-induced sensory
      and pain thresholds.
AB  - OBJECTIVE: We sought to evaluate the potential interaction between acid-sensitive
      chemoreceptors and pressure-sensitive mechanoreceptors. METHODS: Twenty-one
      normal control subjects underwent esophageal balloon distention with a
      commercially produced combined-manometry, acid-infusion, balloon-distention
      catheter. The intraesophageal balloon was localized 10 cm above the lower
      esophageal sphincter. With a mechanical pump, sensory and pain thresholds were
      determined by using sequentially increasing balloon volumes (range 0-23 cc,
      increment 1 cc). A 15-min acid infusion (0.1 N HCl at 6-8 cc/min) or a 0.9 N
      saline infusion was then applied just proximal to the distending balloon,
      followed by a second determination of sensory and pain thresholds. The results of
      the trials before and after acid and placebo were compared. RESULTS: All subjects
      tolerated the procedure. The initial mean volume-to-sensory threshold was 9.1 ml
      (range 5-16), decreasing to 6.2 (range 4-11) after acid infusion (p < 0.005). The
      sensory threshold also decreased from 9.8 ml (range 6-16) to 6.8 ml (range 4-14)
      after saline infusion (p = 0.06). The mean volume-to-pain threshold was 16.0
      (range 14-21) before and 15.2 (range 11-23) after acid infusion and 15.8 (range
      12-20) before and 14.0 (range 10-20) after saline infusion (NS). CONCLUSION: We
      conclude that infused acid has no effect on pain threshold and has a nonspecific
      effect on sensory threshold induced by esophageal balloon distention.

PMID- 9177508
TI  - Endoscopic variceal ligation versus endoscopic variceal ligation and endoscopic
      sclerotherapy: a prospective randomized study.
AB  - OBJECTIVE: To compare endoscopic variceal ligation (EVL) with a combination of
      EVL and endoscopic scelerotherapy (EST) in the secondary prophylaxis of
      esophageal variceal bleeding. METHODS: Fifty patients with esophageal varices due
      to cirrhosis of the liver (38), noncirrhotic portal fibrosis (7), or extrahepatic
      portal venous obstruction (5) were included in the study. These 50 patients were
      randomized to receive either EVL alone or a combination of EVL and EST for
      variceal eradication. Twenty-one patients received EVL alone (group A), and 23
      patients received EVL and EST (group B). In group B, EVLs were performed until
      the varices were reduced to grade II size, and, subsequently, these patients
      underwent low-dose sclerotherapy with 1% polidocanol until variceal eradication
      was achieved. RESULTS: Combined EVL and EST treatment eradicated the varices in a
      significantly greater number of patients then EVL alone (87% vs. 24%; p < 0.05).
      However, significantly more endoscopic sessions were required with combined
      treatment than with EVL alone (5.87 +/- 2.32 vs. 4.28 +/- 1.82; p < 0.05).
      Rebleeding episodes before variceal eradication were similar in the two groups
      (19% vs. 22%). The complications were similar in both the EVL and the EVL-plus
      EST group, ie., deep ulcers (16% vs. 20%), transient dysphagia (20% vs. 32%), and
      stricture (4% vs. 8%). CONCLUSION: Thus, combined EVL and EST treatment
      eradicates varices in a significantly larger number of patients than EVL alone,
      with no extra complications.

PMID- 9177509
TI  - Functional dyspepsia and irritable bowel syndrome: is there a common
      pathophysiological basis?
AB  - OBJECTIVES: Alterations of mechanosensitive thresholds occur in a subset of
      patients with functional dyspepsia and irritable bowel syndrome (IBS). However,
      symptoms associated with these two conditions frequently overlap. It is not known
      how often subjects with and without symptom overlap have abnormal intestinal
      sensory thresholds. Our objective was to assess the pattern of symptoms and small
      intestinal sensory thresholds in patients with functional disorders. METHODS: We
      studied 157 consecutive patients who had undergone extensive diagnostic work-up
      to exclude organic disease. Abdominal symptoms were assessed with a validated
      instrument, and patients were categorized as having functional dyspepsia, IBS, or
      both. With a barostat device, we tested small intestinal mechanosensitive
      function in 22 randomly selected patients from this population (with functional
      dyspepsia, IBS, or both) and 22 healthy controls. RESULTS: Sixty-seven patients
      (43%) reported simultaneous symptoms of functional dyspepsia and IBS, whereas
      symptoms of functional dyspepsia or of IBS alone occurred in 68 (43%) and 22
      (14%) patients, respectively. Thresholds for first perception and maximum
      tolerated pressure (mm Hg +/-SD) were significantly lower in patients (21.0 +/-
      2.0 and 31.0 +/- 1.0) than in controls (32.0 +/- 1.8 and 39.0 +/- 0.9, p <
      0.001). However, thresholds for first perception and maximum tolerated pressure
      did not differ (p > 0.6) in patients with functional dyspepsia alone (20.1 +/-
      3.2 and 28.9 +/- 2.5, n = 9), functional dyspepsia and concomitant IBS (19.9 +/-
      2.7 and 30.7 +/- 2.2, n = 8), or IBS alone (23.5 +/- 2.3 and 33.3 +/- 3.0, n =
      5). CONCLUSIONS: Small intestinal mechanosensitive pathways are disturbed in
      patients with functional dyspepsia and IBS. Differences in the pattern and
      localization of symptoms probably do not reflect differences in small intestinal
      sensory thresholds. Functional dyspepsia and IBS cannot be distinguished on the
      basis of altered small intestinal sensory thresholds.

PMID- 9177510
TI  - Gastric surgery does not increase the risk of developing Barrett's esophagus.
AB  - OBJECTIVE: Barrett's esophagus is currently believed to be related to severe and
      prolonged pathological acid gastroesophageal reflux. However, other factors have
      been discussed, especially pancreatic biliary reflux. To determine the importance
      of pancreatic-biliary reflux in the genesis of Barrett's esophagus, we assessed
      the prevalence of Barrett's esophagus in patients with an intact stomach and in
      those with previous gastric surgery. METHODS: This is a retrospective study in
      which 22,236 upper digestive endoscopy reports were reviewed and classified into
      two groups: intact stomach (n = 21,023) and operated stomach (n = 1,213). In
      turn, these two groups were divided into five subgroups according to surgical
      techniques. In each of the groups and subgroups, we calculated the percentage of
      patients with esophagitis, the percentage of esophagitis patients with Barrett's
      esophagus, and the percentage of Barrett's esophagus patients with complications.
      Results were compared by chi2 test. RESULTS: With regard to the prevalence of
      Barrett's esophagus, we found no significant differences between the study
      groups. CONCLUSIONS: We conclude that previous gastric surgery does not increase
      the risk that esophagitis patients will develop Barrett's esophagus.

PMID- 9177511
TI  - Pancreatic duct stricture length at ERCP predicts tumor size and pathological
      stage of pancreatic cancer.
AB  - OBJECTIVE: To determine whether findings on endoscopic retrograde
      cholangiopancreatography (ERCP) could provide useful prognostic information in
      resectable pancreatic cancer. METHODS: We retrospectively identified 18 patients
      with resectable pancreatic cancer (defined as no evidence of metastatic disease
      or vascular involvement on CT scan) who had undergone ERCP prior to an attempt at
      curative resection between 1991 and 1996. Common bile duct and pancreatic duct
      stricture lengths were measured on ERCP and compared with the size of the
      resected tumor. Magnification was controlled for by comparison with endoscope
      diameter. Stricture length was plotted against actual tumor size, and a
      correlation analysis was performed. RESULTS: Pancreatic duct stricture length
      measured on ERCP correlated with both size (p < 0.001) and stage (p < 0.002) in
      resectable pancreatic cancer. CONCLUSIONS: ERCP may provide useful preoperative
      prognostic as well as diagnostic information in pancreatic cancer.

PMID- 9177512
TI  - Delayed gastric emptying and decreased antral contractility in normal
      premenopausal women compared with men.
AB  - OBJECTIVES: The effects of gender on gastric emptying have not been fully
      elucidated. The aims of this study were to determine how gender affects gastric
      emptying and to see whether any of the observed differences in gastric emptying
      correlate with alterations in antral motility as measured by dynamic antral
      scintigraphy (DAS), cutaneous electrogastrography (EGG), and antroduodenal
      manometry (ADM). METHODS: Nine normal women [age 27.9 +/- 2.2 (mean +/- SEM) yr]
      in the first 10 days of the menstrual cycle and 13 normal men (age 27.5 +/- 1.7
      yr) underwent simultaneous gastric emptying scintigraphy, DAS, EGG, and ADM.
      After an overnight fast and placement of an ADM catheter and EGG electrodes, a 60
      min fasting recording was obtained, followed by ingestion of a 99m Tc-labeled
      solid meal. Measurements for all modalities were acquired every 10-15 min for 180
      min. RESULTS: The gastric T1/2 was longer in women than in men [102 +/- 18 min
      vs. 71 +/- 4 (mean +/- SEM) min, p < 0.05]. A comparison of the gastric emptying
      pattern in women with that in men revealed no difference in proximal gastric
      emptying and lag phase, but in women the terminal slope of emptying was decreased
      compared with that in men (p < 0.05). The contractility measured in mid-antrum by
      DAS was significantly lower for women (p < 0.05). A decrease was also seen in the
      strength of contractions as measured by ADM. CONCLUSIONS: These data demonstrate
      that gastric emptying of solid food in normal young, premenopausal women is
      slower than in age-matched men, even during the first 10 days of the menstrual
      cycle. The findings suggest that the delay is due primarily to altered distal
      gastric motor function. This hypothesis was corroborated by finding decreased
      antral contractility as recorded by both dynamic antral scintigraphy and ADM.
      This study demonstrates the need to use appropriate control values to evaluate
      symptomatic female patients.

PMID- 9177513
TI  - The effect of chronic oral domperidone therapy on gastrointestinal symptoms,
      gastric emptying, and quality of life in patients with gastroparesis.
AB  - OBJECTIVE: Our aim was to determine whether domperidone could improve the
      symptoms of patients with gastroparesis, accelerate gastric emptying, and enhance
      quality of life. METHODS: Seventeen patients (13 women, 4 men; mean age 42.9 yr)
      with documented gastroparesis were evaluated. A baseline gastric emptying study
      was performed using an isotope-labeled solid meal and a follow-up study was
      repeated > or =6 months after initiating domperidone therapy. The severity of
      nausea, vomiting, abdominal pain, and bloating were obtained at baseline and at 6
      month intervals and were graded from 0 to 5 (0 = none, 5 = most severe). Also,
      the number of hospital admissions were noted during the study period. Patients
      were asked to assess their overall health status and quality of life and were
      begun on domperidone 20 mg q.i.d. On average, patients received domperidone for
      23.3 months (range 6-48 months). Domperidone doses ranged from 40 to 120 mg daily
      during the study period. RESULTS: Gastroparesis symptom scores were reduced from
      4.1 +/- 0.22 (mean +/- SEM) to 1.3 +/- 0.2, and hospital admissions were
      decreased significantly during the study compared with before domperidone therapy
      (p < 0.05). At baseline, patients had a 87.3 +/- 3.71% retention of a solid meal
      at 2 hours compared with a 57.2 +/- 5.04% retention during domperidone therapy (p
      < 0.05). Domperidone treatment enhanced the quality of life in 88% of patients.
      The mean prolactin level was 58.9 pg/ml during the study and three patients
      reported gynecomastia. CONCLUSIONS: Chronic domperidone treatment in patients
      with gastroparesis significantly reduced GI symptoms and hospitalizations,
      enhanced quality of life, and accelerated gastric emptying of a solid meal to a
      normal rate. Domperidone successfully treats gastroparesis on a long-term outcome
      basis and has an excellent safety profile.

PMID- 9177514
TI  - The relationship between lactose tolerance test results and symptoms of lactose
      intolerance.
AB  - OBJECTIVE: A standard for the assessment of lactose malabsorption does not exist.
      As measured by lactose tolerance tests, insufficient increase in blood glucose or
      increased breath hydrogen (H2) excretion after lactose ingestion is regarded as
      pathological. In this study, we have tried to elucidate the relationship between
      lactose tolerance test results and symptoms after a lactose challenge. This
      relationship might be an indicator for the validity of the test. METHODS: In a
      prospective study, 309 consecutive patients with suspected lactose malabsorption
      underwent a lactose tolerance test. After consumption of 50 g of lactose, blood
      glucose and breath H2 concentrations were measured. During the test (240 min),
      the severity of bloating, flatulence, abdominal distention, and diarrhea were
      semiquantitatively scored as 0, 1, or 2. The individual sum of these four scores
      was calculated and denoted as the total symptom score (TSS). All subjects were
      classified according to their TSS to compare symptoms with peak breath-H2
      concentration and change in blood glucose concentration, respectively. RESULTS:
      The glucose and breath H2 response were pathological in 51.1 and 39.5% of cases,
      respectively. A stepwise increase in TSS of 1 point was associated with a
      significant increase (p < 0.05) in mean peak H2 concentration. However, a
      significantly lower glucose increment compared with patients with a TSS of 0 was
      found only in patients with a TSS of 2 or 4. The mean symptom score differed
      significantly between the positive and negative breath tests (p < 0.001), but did
      not differ between the positive and negative glucose response results.
      CONCLUSIONS: This study shows that GI symptoms after a lactose challenge are
      strongly associated with the amount of H2 excretion. The relationship between the
      increase in glucose concentration and symptoms after a lactose load is less
      evident. Thus, the H2 breath test seems to be superior to the measurement of
      blood glucose increment as a diagnostic tool in lactose malabsorption, although
      the true predictive value of this test only can be determined after a period of
      dietary treatment.

PMID- 9177515
TI  - The safety of gastrostomy in patients with Crohn's disease.
AB  - OBJECTIVE: To evaluate the safety of gastrostomy tube placement in patients with
      Crohn's disease. METHODS: We retrospectively reviewed the charts of 25 patients
      with Crohn's disease who underwent surgical or endoscopic gastrostomy tube
      placement. Additional follow-up information was obtained by contacting the
      patients by telephone. RESULTS: Twenty-five patients with Crohn's disease
      underwent either surgical or percutaneous gastrostomy tube placement for
      prolonged enteral nutrition or gastric decompression after abdominal surgery.
      Gastrostomies were placed without difficulty in all cases. No major complications
      occurred after the procedures. Minor complications occurred in five patients,
      including one case of local wound infection, one case of persistent pain at the
      gastrostomy site, and three cases of peristomal leakage. These minor
      complications occurred in 22% of those who underwent percutaneous gastrostomy
      tube placement and 16% of those who underwent surgical gastrostomy. There was a
      higher incidence of minor complications in those who underwent gastrostomy for
      gastrointestinal decompression than in those who underwent the procedure for
      nutritional supplementation (14% versus 3.5%). A prior history of fistula
      formation did not predispose to complications related to gastrostomy placement.
      After gastrostomy tube removal, rapid closure of the site occurred in 96%. No
      cases of gastrocutaneous fistula formation occurred during follow-up, which
      ranged from 45 days to 8.7 yr (mean = 2.6 yr). CONCLUSIONS: We conclude that
      gastrostomy placement is safe in patients with Crohn's disease and does not
      result in an increased incidence of peristomal disease or formation of prolonged
      gastrocutaneous fistulas after gastrostomy tube removal.

PMID- 9177516
TI  - Antibiotic prophylaxis for orthopedic prostheses and GI procedures: report of a
      survey.
AB  - OBJECTIVE: To determine the practice recommendations of Program Directors of
      infectious disease training programs with regard to infection prophylaxis for
      patients with prosthetic orthopedic devices who undergo gastrointestinal
      procedures. METHODS: We surveyed Program Directors of infectious disease training
      programs to determine what they recommend when asked about antibiotic prophylaxis
      for patients with orthopedic prostheses who undergo gastrointestinal procedures.
      RESULTS: More than 50% of the respondents agreed that prophylaxis is not
      indicated at any time for these procedures, although there was an almost even
      split when confronted with colonoscopy and polypectomy within 6 months of
      prosthesis insertion. CONCLUSIONS: Most Program Directors agree with the
      recommendations of the American Society for Gastrointestinal Endoscopy and do not
      recommend prophylactic antibiotics for these patients. If antibiotics are chosen,
      they should be the same ones that are recommended for infectious endocarditis by
      The American Heart Association.

PMID- 9177517
TI  - Effects of dietary treatment on bone mineral density in adults with celiac
      disease: factors predicting response.
AB  - OBJECTIVE: Conflicting evidence is reported about the effect of treatment on bone
      mineral density (BMD) in adults with celiac disease (CD). This study analyzed the
      effects on BMD induced by treatment with a calcium-rich, gluten-free diet in
      adults with nonsilent CD. METHODS: In 30 women and 11 men with newly diagnosed
      CD, BMD was measured at the right femur (femoral neck and right Ward's triangle)
      and the lumbar spine by dual-energy x-ray absorptiometry under untreated
      conditions (pretreatment) and after 1-yr treatment with a calcium-rich, gluten
      free diet. RESULTS: On average, posttreatment BMD was greater than pretreatment
      BMD at the lumbar spine (mean +/- SE: 0.907 +/- 0.028 and 0.795 +/- 0.028 g/cm2,
      respectively; p < 0.001), the femoral neck (0.818 +/- 0.023 and 0.741 +/- 0.030
      g/cm2, respectively; p = 0.002), and the Ward's triangle (0.703 +/- 0.025 and
      0.654 +/- 0.025 g/cm2, respectively; p < 0.001). The greatest BMD change (percent
      of baseline) was observed at the lumbar spine (+14.1%), the smallest at the
      Ward's triangle (+7.5%). In the absence of appropriate controls, the BMD change
      expected in the patients under untreated conditions was estimated by regressing
      pretreatment BMD over duration of CD with control for gender and age at which CD
      became clinically evident. The regression coefficient of this analysis indicated
      that 1 yr of untreated CD was associated with a BMD decrease at the lumbar spine
      by 0.00570 g/cm2 (95% confidence interval -0.0103 to -0.0011 g/cm2). The 95%
      confidence interval of the treatment-induced change in BMD at the lumbar spine
      (+0.060 to +0.160 g/cm2) did not overlap the 95% confidence interval of the BMD
      change expected under untreated conditions. A large interindividual variability
      was observed in the BMD response to the treatment: in univariate and multivariate
      analyses, the treatment-induced change in BMD was significantly related to gender
      (greater in women than in men) and to pretreatment age and BMD. CONCLUSIONS: The
      data show that BMD is increased by dietary treatment of CD in most but not all
      adult patients; pretreatment BMD, gender, and pretreatment age predict the bone
      response after a 1-yr treatment.

PMID- 9177518
TI  - Comparison of agar gel (CLOtest) or reagent strip (PyloriTek) rapid urease tests
      for detection of Helicobacter pylori infection.
AB  - OBJECTIVE: Rapid urease tests (RUTs) are used commonly as a convenient method to
      detect Helicobacter pylori infection. New rapid tests have been commercially
      available with promotional literature suggesting enhanced utility. We compared
      CLOtest to a new reagent strip RUT, PyloriTek. METHODS: Gastric antral mucosal
      biopsy specimens were obtained from 102 patients for comparison between CLOtest
      and PyloriTek (204 specimens). Biopsy specimens obtained from a nearby area were
      stained using the Genta stain for determination of H. pylori status. The RUT to
      be used first was selected randomly. RESULTS: Sixty-five of the 102 patients had
      peptic ulcer disease, two had gastric cancer, and 35 had dyspepsia; 61 patients
      had active H. pylori infection. There were one false-negative and three false
      positive CLOtest results, compared with one false-negative and 13 false-positive
      PyloriTek results (p < 0.02 for incorrect categorization with PyloriTek).
      Sensitivity and specificity were 98 and 92% compared with 98 and 68% for CLOtest
      and PyloriTek, respectively. An erroneous categorization of H. pylori status
      occurred in 3.9% (95% confidence interval [CI]: 1-9.7%) with CLOtest compared
      with 13.7% (95% CI: 7.7 -22%) with PyloriTek. When the PyloriTek was scored at 1
      h (0-1 h) after obtaining the specimen, the accuracy improved; erroneous
      categorization of H. pylori status occurred in only 2.9% (95% CI: 0.6-8.3%).
      CONCLUSION: Used according to manufacturer instructions, the new reagent strip
      RUT PyloriTek has too many false-positive results for use in a clinical
      situation. In contrast, when the test was interpreted within 1 h, accuracy was
      comparable to that of CLOtest.

PMID- 9177519
TI  - The prevalence of Helicobacter pylori infection among inhabitants and healthy
      employees of institutes for the intellectually disabled.
AB  - OBJECTIVES: The prevalence of Helicobacter pylori infection varies in the
      Netherlands from 5% in children to about 50% in the elderly. In the
      institutionalized intellectually disabled, a high prevalence of infection has
      been reported. It is unknown whether there are specific risk factors to obtain H.
      pylori infection in this population, and whether employees of such institutes are
      at risk for H. pylori infection. METHODS: Therefore, we analyzed the
      seroprevalence of H. pylori antibodies by ELISA among 338 intellectually disabled
      inhabitants and 254 employees of two institutes. H. pylori-positive patients were
      compared with H. pylori-negative controls. The intellectually disabled and the
      employees were evaluated for possible risk factors. RESULTS: Of the 338
      intellectually disabled, 280 (82.8%, median age 51 yr) were infected with H.
      pylori. This rate is significantly higher than the prevalence of H. pylori in the
      Dutch population. The presence of H. pylori was significantly associated with
      male gender, longer duration of institutionalization, an IQ < 50, rumination, and
      a history of upper abdominal symptoms. Of the 254 employees, 69 (27.2%) were
      infected, which is equal to the rate for the total Dutch population. The presence
      of H. pylori infection among employees was, however, significantly associated
      with a higher level of physical contact with the intellectually disabled, longer
      duration of employment, and having upper abdominal symptoms. CONCLUSIONS:
      Intellectually disabled persons are at high risk of developing H. pylori
      infection. Employees with close physical contact to the intellectually disabled
      population for a considerable period of time are also at increased risk. H.
      pylori infection should be considered a job attributable risk in this profession.

PMID- 9177520
TI  - Relation of lactoferrin levels in gastric mucosa with Helicobacter pylori
      infection and with the degree of gastric inflammation.
AB  - OBJECTIVES: Lactoferrin (Lf) is an iron-binding glycoprotein present in milk,
      lacrimae, saliva, and gastroduodenal secretions. In vitro studies disclosed
      contradicting results regarding the relation of Lf with Helicobacter pylori (HP)
      infection. This study aimed to investigate the relationship between the gastric
      mucosal concentration of Lf and HP infection of the stomach. The relationship of
      the gastric mucosal level of Lf with the gastric mucosal concentration of
      interleukin-8 (IL-8) and with the intragastric ammonia levels was also assessed.
      In addition, the gastric mucosal Lf levels before and after irradication of HP
      infection were also evaluated. METHODS: This study was composed of 27 HP-positive
      and 12 HP-negative patients with chronic gastritis. Gastric mucosal biopsy
      specimens were obtained from all subjects by endoscopy, and the degree of
      histological inflammatory changes were assessed according to the Sydney system.
      The gastric mucosal levels of Lf and IL-8 were measured by immunoassays.
      Assessment of the effect of therapy on the gastric mucosal level of Lf was
      performed in 10 patients with HP-associated duodenal ulcer. RESULTS: Lf, IL-8,
      and ammonia levels were significantly higher in patients with HP-positive
      gastritis compared with those with HP-negative gastritis in both the antrum and
      the gastric body. Histologically, the degree of inflammatory changes correlated
      significantly with the Lf levels in the gastric mucosa. Furthermore, the degree
      of HP colonization was more significant in biopsy samples from the antrum than in
      those from the corpus of the stomach. The gastric mucosal levels of Lf and IL-8
      correlated significantly in the antrum and the gastric body. The ammonia
      intragastric level significantly correlated with the mucosal Lf level in the
      antrum and in the gastric body. Therapy significantly decreased the Lf levels in
      the gastric mucosa of the antrum (p < 0.005) and the gastric body (p < 0.005).
      CONCLUSION: The results of the present investigation showed, for the first time
      in vivo, that Lf concentration is increased in the biopsy specimens of patients
      with HP-related gastritis, and that the levels of Lf correlate significantly with
      the degree of inflammation of the gastric mucosa. The gastric mucosal level of Lf
      may constitute an excellent marker of HP infection.

PMID- 9177521
TI  - Value of Doppler ultrasound parameters of portal vein and hepatic artery in the
      diagnosis of cirrhosis and portal hypertension.
AB  - OBJECTIVES: This prospective study was designed to assess the sensitivity and
      specificity of Doppler ultrasound parameters in the diagnosis of cirrhosis and
      portal hypertension. METHODS: Portal and hepatic arterial Doppler ultrasound was
      performed on 76 patients with cirrhosis and esophageal varices and on 73 age- and
      sex-matched controls. The parameters evaluated were portal venous velocity and
      hepatic arterial pulsatility index. The liver vascular index was calculated as
      the ratio of portal venous velocity to hepatic arterial pulsatility index.
      RESULTS: Portal venous velocity was significantly lower (11.0 +/- 2.4 vs 15.9 +/-
      2.8 cm/s, p < 0.001) and hepatic arterial pulsatility index was significantly
      higher (1.28 +/- 0.18 vs 0.95 +/- 0.17,p < 0.001) in patients than in controls.
      Thus, the liver vascular index was significantly lower in patients than in
      controls (8.7 +/- 2.1 vs 17.2 +/- 4.3 cm/s, p < 0.001). The sensitivity and
      specificity of these parameters in the detection of cirrhosis and portal
      hypertension was then analyzed with the receiver operating characteristic curve.
      The best cut-off values were considered to be 13 cm/se of portal venous velocity
      and 1.1 of hepatic arterial pulsatility index, showing a sensitivity and
      specificity of 83, 85, 84, and 81%, respectively. The best cut-off value of the
      liver vascular index was 12 cm/s with a sensitivity and specificity of 97 and
      93%, respectively. CONCLUSIONS: The liver vascular index is a high sensitive and
      specific Doppler ultrasound parameter in the diagnosis of cirrhosis and portal
      hypertension.

PMID- 9177522
TI  - Protein plugs cause symptoms in patients with choledochal cysts.
AB  - OBJECTIVES: Symptoms in patients with choledochal cysts are believed to be caused
      by pancreaticobiliary maljunction. However, this anomaly alone cannot explain the
      occurrence of symptoms. The aim of this study was to elucidate the etiology of
      the symptomatology in patients with choledochal cysts. METHODS: Clinical data and
      preoperative and operative cholangiopancreatography were reviewed in 55
      consecutive patients with choledochal cysts seen between 1980 and 1996. RESULTS:
      The bile duct was significantly larger in the symptomatic phase than in the
      asymptomatic phase. External biliary drainage resulted in rapid resolution of
      symptoms in 11 patients. A radiolucent filling defect in the pancreaticobiliary
      duct was found in 22 patients (40.0%). The defects were in the common channel in
      15 patients and near the common channel in 7 patients. Filling defects
      disappeared spontaneously or after irrigation in 19 patients. In three patients,
      the material in the common channel removed during surgery was fragile and
      consisted of more than 98% protein. CONCLUSION: The filling defects were protein
      plugs. The simultaneous occurrence of symptoms and signs may be explained by
      disturbances in bile and pancreatic secretory flow caused by a protein plug in
      the common channel.

PMID- 9177523
TI  - Evaluation of rectal mucosal hemodynamics in patients with liver cirrhosis using
      reflectance spectrophotometry.
AB  - OBJECTIVES: Portal hypertensive colonopathy is observed in patients with liver
      cirrhosis. To determine the correlation between rectal mucosal hemodynamics and
      portal hypertensive colonopathy, we observed rectal mucosal findings and measured
      rectal mucosal hemodynamics in patients with liver cirrhosis. METHODS: Thirty
      four patients with liver cirrhosis and 16 healthy control subjects were
      simultaneously examined for rectal mucosal findings by colonoscopy and indices of
      rectal mucosal Hb concentration (RHb) and rectal mucosal oxygen saturation by
      reflectance spectrophotometry. Endoscopic findings in the rectal mucosa of
      patients with liver cirrhosis included vascular ectasias, blue veins, and
      varices. We investigated the relationship between rectal mucosal hemodynamics and
      clinical parameters of liver cirrhosis (Child-Pugh classification, the amount of
      indocyanine green remaining in the blood 15 min after its injection, and
      ascites). Patients with hepatocellular carcinoma, colonic cancer, multiple
      colonic polyps, or severe anemia were excluded. RESULTS: Rectal mucosal lesions
      were observed in 11 patients with liver cirrhosis (32.4%). In the hemodynamic
      studies, we found significantly increased RHb values in the cirrhosis group as
      compared with the control group. On the other hand, there was no significant
      change in rectal mucosal oxygen saturation between the two groups. A significant
      increase in RHb was observed in patients with rectal mucosal lesions in the
      cirrhosis group. RHb in the cirrhosis group correlated with grade of Child-Pugh
      classification. Increased RHb decreased in parallel after portal decompression by
      creation of a transjugular intravenous portosystemic stent shunt. CONCLUSIONS:
      The rectal mucosal lesions in liver cirrhosis correlate with an increase in RHb,
      which correlates with portal hypertension.

PMID- 9177524
TI  - Changes in liver function parameters after occlusion of gastrorenal shunts with
      balloon-occluded retrograde transvenous obliteration.
AB  - OBJECTIVE AND METHODS: To evaluate the effects of portal blood flow on liver
      function, this pilot study investigated the correlation between changes in portal
      blood flow as measured by image-directed Doppler ultrasonography and liver
      function tests in nine patients with cirrhosis who were treated with balloon
      occluded retrograde transvenous obliteration. All patients had large gastric
      varices and prominent gastrorenal shunts. RESULTS: Treatment caused a significant
      increase (p < 0.01) in portal blood flow; we documented reversion from
      hepatofugal to hepatopetal portal flow in one patient and increases in
      hepatopetal flow from 5.4 +/- 1.1 to 7.85 +/- 1.4 cm/s (mean +/- SD) in eight
      patients. All patients showed decreases in gastric variceal size. However, portal
      pressure rose significantly in all patients after treatment from 25.4 +/- 7.6 to
      30.7 +/- 5.8 mmH2O (n = 7, mean +/- SD), and two of nine patients had worsening
      of esophageal varices. All nine patients showed improvement in the 15-min
      retention rate of indocyanine green from 31.8 +/- 16.1 to 21.8 +/- 12.4% (mean +/
      SD, p < 0.01), whereas seven patients showed increased serum albumin levels
      after treatment. CONCLUSIONS: These results suggest balloon-occluded retrograde
      transvenous obliteration increases hepatic portal blood flow, which may be
      accompanied by improvements in liver function.

PMID- 9177525
TI  - Clinical application of a new monoclonal antibody (19B7) against PIVKA-II in the
      diagnosis of hepatocellular carcinoma and pancreatobiliary malignancies.
AB  - OBJECTIVES: A new monoclonal antibody (19B7) against prothrombin induced by
      vitamin K absence or antagonist-II (PIVKA-II) was clinically applied in patients
      diagnosed with hepatocellular carcinoma and pancreatobiliary malignancies, and
      the results were compared with those obtained using the conventional monoclonal
      antibody (MU-3) against PIVKA-II. METHODS: The assays were the standard E-1023
      using MU-3, a high sensitivity kit using MU-3 and a highly sensitive avidin
      biotin complex method, and a new monoclonal antibody (19B7) kit. RESULTS: The
      rate of PIVKA-II positivity in patients with hepatocellular carcinoma (n = 182)
      was 44% with E-1023, 55.5% with the high sensitivity kit, and 58.2% with the new
      monoclonal antibody kit. Small liver cancers <2 cm in diameter (n = 45) had a
      positivity rate of 15.6% with E-1023, 26.7% with the high sensitivity kit, and
      31.1% with the new monoclonal antibody kit. The incidence of PIVKA-II positivity
      in patients with pancreatobiliary carcinoma (n = 91) was 29.7% with the high
      sensitivity kit and 52.7% with the new monoclonal antibody kit. The PIVKA-II
      ratio (plasma concentration with the high sensitivity kit/plasma concentration
      with the new monoclonal antibody kit) was calculated as > 1.0 in 89 of the 113
      (78.8%) patients with hepatocellular carcinoma with the new monoclonal antibody
      kit assay level above 0.002 arbitrary units/ml, compared with <1.0 in almost all
      patients with pancreatobiliary malignancies. CONCLUSIONS: MU-3 has much greater
      affinity for PIVKA-II in hepatocellular carcinoma than does 19B7, whereas 19B7
      has much greater affinity for PIVKA-II in pancreatobiliary malignancies than does
      MU-3. The new monoclonal antibody, 19B7, is useful for diagnosing hepatocellular
      carcinoma and can also distinguish patients with hepatocellular carcinoma from
      those with other pancreatobiliary malignancies when combined with a PIVKA-II
      assay using the conventional monoclonal antibody, MU-3.

PMID- 9177527
TI  - Diffuse esophageal glycogenic acanthosis: an endoscopic marker of Cowden's
      disease.
AB  - Cowden's disease is a rare autosomal dominant condition characterized by multiple
      hamartomas of ectodermal, endodermal, and mesodermal origin affecting many organ
      systems. Gastrointestinal manifestation includes the formation of multiple polyps
      of various benign histopathological types throughout the alimentary tract. Recent
      literature suggests that the frequency of gastrointestinal involvement is
      approximately 70-85%. The diagnosis of Cowden's disease, however, relies mainly
      on subtle dermatologic findings, which may not be obvious to the
      gastroenterologist. We describe a patient with Cowden's disease and review the
      English literature on the topic of gastrointestinal polyposis and Cowden's
      disease. These studies suggest that gastrointestinal polyposis is commonly found
      in this disease, and that diffuse esophageal glycogenic acanthosis is a
      characteristic feature of Cowden's disease. We propose that the finding of
      extensive glycogenic acanthosis in the presence of other benign gastrointestinal
      polyposis should be considered pathognomonic for the diagnosis of Cowden's
      disease.

PMID- 9177526
TI  - Ursocholic acid, a hydrophilic bile acid, fails to improve liver function
      parameters in primary biliary cirrhosis: comparison with ursodeoxycholic acid.
AB  - OBJECTIVE: To compare the effect of short term feeding of ursocholic acid, a
      hydrophilic bile acid, as the unconjugated acid and the taurine conjugate, on
      clinical and biochemical features and bile acid metabolism with that of
      ursodeoxycholic acid in four patients with primary biliary cirrhosis. METHODS:
      Four patients with stage II primary biliary cirrhosis were studied. Two were fed
      ursocholic acid (900 mg/day), and two were given tauroursocholate (900 mg/day) in
      three divided doses. After 1 month, all patients were given 900 mg/day of
      ursodeoxycholic acid. Fasting serum, bile, and 24-hour urine levels were measured
      before and at the end of ursocholic acid and tauroursocholate feeding and after 1
      month of ursodeoxycholic acid feeding. Clinical and biochemical symptoms were
      measured by routine hospital methods, and bile acids were measured by gas-liquid
      chromatography. RESULTS: One month of ursocholic acid or tauroursocholate feeding
      did not improve clinical or biochemical findings in any patient. Approximately 21
      25% ursocholic acid was present in the serum and bile, with substantial
      metabolism to deoxycholic acid. Increased ursocholic acid was excreted in the
      urine. In comparison, ursodeoxycholic acid improved biochemical parameters and
      was 45-65% enriched in the serum and bile. CONCLUSION: Ursocholic acid as the
      free bile acid or as taurine conjugate, although more hydrophilic, is poorly
      enriched in serum and bile and is ineffective in patients with primary biliary
      cirrhosis.

PMID- 9177528
TI  - Menetrier's disease: a new variant with duodenal involvement.
AB  - Menetrier's disease is a rare cause of hypertrophic gastropathy, usually confined
      to gastric body and fundus, which is characterized by giant rugae,
      hypoalbuminemia, and foveolar hyperplasia. The etiology of this disease is still
      unknown. We report a case of a 74-yr-old man who had dyspepsia, hypoalbuminemia,
      weight loss, and diffuse polypoid, nodular lesions affecting the whole stomach
      and proximal duodenum on gastroscopy and barium meal study. The histology of
      gastric and duodenal mucosal lesions fulfilled the diagnosis of Menetrier's
      disease, that was not described to involve duodenum in the literature. The
      disease resolved clinically, endoscopically, and pathologically after therapy
      with famotidine for 3 months. We speculated that extensive pyloric metaplasia and
      then foveolar hyperplasia of duodenum in this patient might be a variant of
      Menetrier's disease with favorable clinical course.

PMID- 9177529
TI  - Orthotopic liver transplantation improves small bowel motility disorders in
      cirrhotic patients.
AB  - Altered small intestinal motility has been observed in patients with liver
      cirrhosis. Its pathophysiology remains to be defined. Our aim was to investigate
      the effect of orthotopic liver transplantation on small intestinal dysmotility in
      patients with liver disease. Two patients were studied both before and after
      orthotopic liver transplantation. Abnormal migrating motor complex activity and
      prominent clustered contractions present preoperatively normalized within 6
      months after the surgical procedure. This finding might represent an additional
      benefit of liver transplantation considering that altered motility may be
      involved in bacterial overgrowth and infections observed in these patients.

PMID- 9177530
TI  - Hyperlipidemia as the first biochemical manifestation of primary hepatic
      amyloidosis.

PMID- 9177531
TI  - Utilization of an esophageal stent for subsequent placement of a percutaneous
      endoscopic gastrostomy tube.

PMID- 9177532
TI  - Duodenal obstruction secondary to a metastasis from an adenocarcinoma of the
      cecum: a case report.
AB  - Metastatic tumors to the gastrointestinal tract are rare; the stomach and small
      bowel are the most common organs involved. Lung cancer, renal cell carcinoma,
      breast carcinoma, and malignant melanoma are the most common primary tumors
      metastatic to the duodenum. We report a metastasis to the duodenum from an
      adenocarcinoma of the cecum presenting as a duodenal obstruction 4.5 yr after the
      surgical resection of the primary tumor. The condition of the patient was
      temporarily controlled with the implantation of an endoduodenal metallic
      prosthesis as a palliative measure.

PMID- 9177533
TI  - Mesenteric ischemia secondary to cocaine abuse: case reports and literature
      review.
AB  - In summary, we report two cases of mesenteric ischemia following cocaine abuse in
      young women. In such cases it is always difficult to prove a direct causal
      relationship between the abuse of cocaine and mesenteric ischemia. Both our
      patients were relatively young (in their thirties) and did not have any history
      of atherosclerosis, and their urine toxicity screens were positive for the use of
      cocaine. Cocaine-related hospital visits are on the increase. Mesenteric ischemia
      should be considered in the differential diagnosis when evaluating a young
      patient with a history of cocaine abuse presenting with an acute abdomen.

PMID- 9177534
TI  - Eosinophilic esophagitis: case report and clinical perspective.

PMID- 9177535
TI  - Portal hypertensive stomapathy: a newly described entity and its successful
      treatment by placement of a transjugular intrahepatic portosystemic shunt.
AB  - We report the case of a 68-yr-old woman who had previously undergone a total
      colectomy and ileostomy for Crohn's disease limited to the colon. She
      subsequently had recurrent episodes of severe stomal bleeding and was discovered
      to have micronodular cirrhosis. No definite stomal varices were seen by visual
      inspection, stomal endoscopy, stomal endosonography, or angiography.
      Nevertheless, multiple discrete, punctate bleeding pints were seen on the
      external mucosal surface of the stoma (not at the mucocutaneous junction).
      Despite undergoing numerous modes of treatment, the bleeding continued. The only
      successful and effective form of treatment was the placement of a transjugular
      intrahepatic portosystemic shunt.

PMID- 9177536
TI  - Occult gastric cancer presenting as cor pulmonale resulting from tumor cell
      microembolism.
AB  - Cor pulmonale resulting from tumor emboli is a rare presentation of gastric
      cancer, and only six similar cases have been reported in the English literature.
      We report the case of a 37-yr-old woman presenting with dyspnea who died of cor
      pulmonale. Autopsy revealed signet cell carcinoma of te stomach with intra
      abdominal metastasis and right ventricular hypertrophy. There were no macroscopic
      pulmonary emboli or parenchymal lesions, but more than 60% of the small pulmonary
      arteries and arterioles were occluded. In most vessels, fibrocellular intimal
      proliferation was the major finding with only a few entrapped tumor cells.

PMID- 9177537
TI  - Sclerosing mesenteritis: an unusual cause of abdominal pain in an HIV-positive
      patient.
AB  - Sclerosing mesenteritis is a rare, idiopathic, and benign mesenteric lesion that
      is characterized by fat necrosis, fibrosis, and chronic inflammation. We report a
      case of sclerosing mesenteritis presenting as recurrent abdominal pain in an HIV
      positive patient. Because of the wider differential diagnosis in such cases, the
      patient underwent an extensive workup culminating in a laparoscopy with biopsy.
      Tamoxifen has been shown to be useful in the treatment of desmoid tumors and
      idiopathic retroperitoneal fibrosis. We present the first case of sclerosing
      mesenteritis to respond to tamoxifen therapy. Because this drug is relatively
      safe and simple to dose, its utility as therapy for patients with this benign but
      debilitating disease should be considered.

PMID- 9177538
TI  - Biliary obstruction caused by endoscopic band ligation of a duodenal varix.

PMID- 9177539
TI  - Spontaneous rupture of a bile duct and its endoscopic management in a patient
      with Caroli's syndrome.
AB  - Caroli's syndrome is a condition of cystic dilation of intrahepatic bile ducts
      that communicate with the extrahepatic biliary tree. Patients with Caroli's
      syndrome are prone to develop several complications. These include bacterial
      cholangitis, biliary sludge, calculi, and cholangiocarcinoma. We describe an
      adult patient with Caroli's syndrome in whom spontaneous rupture of a bile duct
      developed with consequent biliary peritonitis, which was successfully managed
      with endoscopic stent placement.

PMID- 9177540
TI  - Small duodenal somatostatinoma with high plasma somatostatin level.

PMID- 9177541
TI  - Expandable metal stents for treatment of colonic obstruction: viable therapeutic
      alternative?

PMID- 9177542
TI  - Once is enough.

PMID- 9177543
TI  - Protease inhibitors for prevention of ERCP pancreatitis: can we afford the price
      of success?

PMID- 9177544
TI  - Gallstone formation after open cardiac surgery.

PMID- 9177545
TI  - Parietal cell mass, hydrochloric acid secretion, and Helicobacter pylori.

PMID- 9177546
TI  - Incorrect gold standard in diagnostic tests for Helicobacter pylori.

PMID- 9177547
TI  - The spleen as a storage pool in lipid metabolism.

PMID- 9177548
TI  - The effects of glucose or lipid infused intravenously or intragastrically on
      voluntary food intake in the rat.
AB  - Glucose or lipid was infused intravenously (IV) or intragastrically (IG) 30 min
      before and also during the 17 h when rats were fed both a high-carbohydrate diet
      and a high-fat diet. Three-day infusions of 28.1 kcal of glucose reduced daily
      food intake by 19.7 +/- 1.9 kcal/day, representing an oral intake reduction
      equivalent to 70% of each calorie infused. Infusions of 28.1 kcal of lipid
      reduced baseline food intake by 11.2 +/- 2.7 kcal/day or 40% of each calorie
      infused (p < 0.0005). Furthermore, infusions of nutrient IG reduced baseline food
      intake by 17.6 +/- 2.1 kcal/day or 63% of each calorie infused, and infusions of
      nutrient IV reduced baseline food intake by 13.7 +/- 2.6 kcal/day or 49% of each
      calorie infused (p < 0.05). Also, glucose infusions (1.0 kcal/40 min) reduced 10
      min food intake from saline baseline levels by 1.1 +/- 0.5 kcal, but lipid
      infusions had no effect. Infused glucose is more effective than lipid in
      inhibiting short-term intake, daily food intake, and intake of high-carbohydrate
      diet, and IG infusion is more effective than IV infusion in inhibiting daily food
      intake.

PMID- 9177549
TI  - Effect of atenolol on nocturnal sleep and temperature in young men: reversal by
      pharmacological doses of melatonin.
AB  - To examine the physiological role of melatonin in sleep, nocturnal melatonin
      secretion was suppressed using 100 mg oral atenolol in two studies. In Study 1,
      nocturnal sleep was recorded in 8 young men over 4 nights. Subjects received
      atenolol on one of the last 2 nights and showed significantly increased total
      wake time (TWT) and wakefulness after sleep onset (WASO), as well as decreased
      REM sleep and slow-wave sleep (SWS). When melatonin (total 5 mg) was given after
      atenolol on the other night, the changes in TWT, WASO, REM, and SWS were
      reversed. In Study 2, sleep onset latencies (SOL) and core temperature (Tc) of 10
      young men were measured for 3 nonconsecutive nights. In a cross-over design,
      atenolol given on one night significantly suppressed urinary 6
      sulphatoxymelatonin (6s-aMT) production and increased hourly measures of Tc and
      SOL relative to baseline night values. Oral melatonin (3 mg), administered after
      atenolol, reversed the changes in Tc and SOL. These results suggest that
      endogenous melatonin may assist in the maintenance of normal sleep architecture
      (Study 1) and also increase nocturnal sleep propensity by hypothermic effects
      (Study 2).

PMID- 9177550
TI  - Feed pecking in young chickens: new techniques of evaluation.
AB  - Three techniques were compared: automated recording (A) of 2 h of feeding
      activities conveyed to a computer by constantly connected electronic balances,
      videotaping (V) of a closeup of the head of a chick during a feed-pecking session
      analyzed by focal sampling at reduced speed (16 times slower), strength of
      pecking (S) at feed particles recorded from a feeder-weight signal conveyed to a
      computer by a customized electronic balance at rapid speed (24 times/s). These
      techniques were applied to 16-18-day-old chicks fed either a complete feed or a
      split diet (whole grain wheat + a complementary feed). The two feeds had similar
      pellet forms. The complementary feed particles were eaten at a slower rate than
      the complete feed particles (A and V techniques). Wheat grains were pecked with a
      weaker measured strength than the pellets (technique S). Two pecks of three did
      not result in prehension of a feed particle and were categorized as "exploratory"
      pecks. For 75% of the time during a continuous pecking session the head of the
      chick was in a static position, suggesting a long period of observation of the
      feed between 2 consecutive pecks. Videotaping with slow-motion focal sampling (V)
      offers potential development for the study of food intake behavior of chickens.

PMID- 9177551
TI  - Fat gain in female swimmers.
AB  - The association between diet and body composition was investigated in 6 elite
      female swimmers subjected to a 13-month nutritional supervision and in 11 female
      untrained subjects matched for fat-free mass. The impact of a 2-month
      interruption of training on diet and body composition was also studied in the
      swimmers. A positive correlation was observed between the percentage of dietary
      energy as fat and percent body fat in the untrained subjects (r = 0.68, p <
      0.05). When values of the swimmers were incorporated in the regression analysis,
      the correlation coefficient remained the same. Following detraining for 2 months,
      a 4.8-kg body weight gain, including 4.3 kg fat mass, was observed. The energy
      equivalent of these morphological changes was 170 MJ and corresponded to about
      the amount of energy that would have been normally expended during this
      detraining period. In conclusion, these results suggest that the association
      between diet and body composition is not altered by exercise training, and that
      body fat gain occurs in response to detraining, perhaps to promote the
      restoration of energy and fat balance.

PMID- 9177552
TI  - Characteristics of glucose and maltose preloads that inhibit feeding in 12-day
      old rats.
AB  - Nonvolumetric inhibitory control of food intake during independent ingestion was
      studied in rats on postnatal day 12. Pups received either sham intubation or
      equivolumetric (5% BW) preloads of 20% (w/v) glucose, 20% maltose, 20% 2-deoxy-D
      glucose (2-DG), 0.9% NaCl, 200 mg soybean trypsin-inhibitor (SBTI) or distilled
      water, 5 min prior to 30-min access to a milk diet spread on the floor of a
      beaker. To investigate if endogenous cholecystokinin mediated any of the
      inhibitory effects of the preloads on intake, pups were injected IP with 1 mg/kg
      devazepide, a specific CCK(A) receptor antagonist, or with vehicle 30 min prior
      to the intake test. All preloads reduced intake (measured by percent body weight
      gain) compared to sham intubation. Glucose (20%) reduced intake significantly
      more than 0.9% saline, but not more than the preload of 20% 2-DG. This suggests
      that the effect of glucose can be accounted for by its preabsorptive osmotic
      properties because 2-DG is not actively transported or metabolized. The
      inhibitory effect of 20% maltose may also be due to its osmotic load, but these
      experiments did not provide clear evidence for this. Cholecystokinin apparently
      did not mediate the effect of any of the preloads except SBTI, because devazepide
      only reduced the inhibition produced by a preload of SBTI. These results provide
      further evidence that hypertonic stimuli in the stomach or small intestine
      provide inhibitory control of food intake by postnatal day 12.

PMID- 9177553
TI  - The effect of centrally administered CCK-receptor antagonists on food intake in
      rats.
AB  - Cholecystokinin (CCK) receptors are classified as two subtypes, designated CCK(A)
      and CCK(B), and both subtypes are found in brain and peripheral tissues of rats.
      CCK-8 has been shown to act peripherally to reduce meal size, and this satiating
      action can be blocked by CCK(A)-receptor antagonists. Recent evidence suggests
      that, in addition to the peripheral action of CCK, central CCK mechanisms may
      also be involved in satiety. Central administration of proglumide, a mixed CCK
      receptor antagonist (CCK(A) > CCK(B)) has been shown to increase food intake and
      block the satiating effect of peripherally administered CCK-8 (15). In an attempt
      to replicate and extend these results, rats were given injections of proglumide
      or selective CCK-receptor antagonists into the lateral ventricle prior to a
      peripheral injection of CCK-8 or saline. Only proglumide stimulated an increase
      in 30-min test meal intake and attenuated the satiating effect of CCK-8. Two
      selective CCK(A)-receptor antagonists, lorglumide and devazepide, did not
      increase intake significantly when given alone, and they did not attenuate the
      effect of peripherally administered CCK-8. The selective CCK(B)-receptor
      antagonist, L365,260, reduced intake at all doses tested except the lowest. The
      lowest dose did not increase intake when given alone and did not attenuate the
      inhibitory effect of CCK on test-meal intake. Finally, a combination of
      devazepide and L365,260 did not increase intake or block the effect of
      peripherally administered CCK-8. These results suggest that CCK released by
      neurons in the brain and acting on central CCK(A)- and CCK(B)-receptors is not
      necessary for the control of meal size or for the satiating effect of
      peripherally administered CCK-8 in rats under our experimental conditions.

PMID- 9177554
TI  - Taste in chimpanzees II: single chorda tympani fibers.
AB  - Data are presented from 48 taste fibers in chorda tympani nerves of 10
      chimpanzees during taste stimulation with 29 stimuli. The results demonstrated a
      higher taste fiber specificity than in any other mammalian species reported;
      breadth of tuning equals 0.3. Hierarchical cluster analysis separated an S
      cluster (50% of all fibers), an N-cluster (31%), and a Q-cluster (19%). The S
      cluster showed the highest specificity. Its fibers responded, with few
      exceptions, to every sweetener tested, including the sweet proteins brazzein and
      monellin. The response grew with increasing sweetener concentration. A large
      response to one sweetener was generally accompanied by a large response to all
      other sweeteners, and vice versa. Except for one broadly tuned fiber, the fibers
      of the S-cluster never responded to the bitter compounds. The fibers of the Q
      cluster were more broadly tuned than any other fibers. Quinine hydrochloride was
      their best stimulus, but most fibers were also stimulated by KCl and NaCl with
      amiloride. Acids stimulated some of these fibers. The N-cluster could be divided
      into 3 subclusters: an Na-subcluster (3 fibers), Na-K subcluster (10 fibers), and
      M-subcluster (3 fibers). The Na-fibers responded strongly to, and were quite
      specific to, NaCl and LiCl stimulation but not to KCl, and fibers of the Na-K
      subcluster responded equally well to NaCl and KCl. The response to NaCl was
      suppressed by amiloride in the fibers of the Na-subcluster, but not in the fibers
      of the Na-K subcluster. Umami compounds elicited the strongest responses in the M
      subcluster.

PMID- 9177555
TI  - P300 sequence effects, probability, and interstimulus interval.
AB  - Probability and interstimulus interval effects on P3(00) event-related potential
      (ERP) stimulus sequences were examined in 2 experiments. ERPs were elicited with
      an auditory-discrimination paradigm in which subjects were instructed to detect
      target stimuli from a series of target (T) and standard (S) tones that were
      varied by randomly presenting 1 of 4 sequence patterns (SS, TS, TT, ST).
      Experiment 1 manipulated target stimulus probability as either 0.33 or 0.67;
      Experiment 2 kept target probability at 0.33 and manipulated the interstimulus
      interval (ISI) as either 2 or 6 s. Increases in target stimulus probability
      produced smaller P300 amplitudes that were additive with stimulus sequence type.
      ISI did not reliably affect P300 amplitude, although ISI interacted with stimulus
      sequence. P300 latency from the stimulus sequences was influenced weakly by the
      probability and ISI factors, with few consistent sequence effects obtained for
      the N1, P2, and N2 potentials. The results suggest that even relatively short
      sequences can affect P300 amplitude in the same way as longer sequences: as the
      number of standard stimuli preceding the target increased, P300 amplitude
      increased. The theoretical implications of the findings are discussed in the
      context of applied testing situations.

PMID- 9177556
TI  - Central vs. peripheral spontaneous behavioral abnormalities in experimental
      hepatic encephalopathy.
AB  - The most common behavioral disturbance reported in experimental chronic hepatic
      encephalopathy (HE) refers to changes in spontaneous activities in an open field
      in the portacaval-shunted (PCS) rat. A major problem at present is that not all
      of these findings of abnormal PCS behavior are in agreement. We, therefore,
      investigated the total, central, and peripheral locomotor and rearing activities
      in an open field 2 and 6 months after PCS surgery. The results revealed that, 2
      months after surgery, locomotor and rearing activities were lower in PCS rats
      compared to controls. At 6 months, a partial remission of the behaviors had
      occurred. Clearly though, as pointed out by the peripheral behavioral recordings,
      the hypoactivity persisted and, interestingly, central locomotor activity as
      higher in PCS rats than in controls. This novel finding may be attributed to the
      special study of central vs. peripheral components of the spontaneous open-field
      behavior in experimental chronic HE. Our observations may also help explain some
      of the seemingly discrepant results available in the literature.

PMID- 9177557
TI  - Sex differences and the development of social behavior in a marsupial, the gray
      short-tailed opossum (Monodelphis domestica).
AB  - The effects of sex and age on social behavior were examined in gray short-tailed
      opossums (Monodelphis domestica), small didelphid marsupials. Each animal
      received five behavior test batteries spanning prepubertal to postpubertal ages.
      Each test battery consisted of two tests with animals of the same age, one with a
      male and one with a female. Precopulatory behavior toward females, intermale
      fighting requiring test interruptions as well as scent marking behavior were seen
      at higher levels in males than in females and were seen more frequently around
      and after puberty than before puberty. Females showed more threat behavior than
      males in mixed-sex and in same-sex interactions. This sex difference was apparent
      after puberty in tests with male partners and prior to as well as around puberty
      in tests with female partners. Because climbing over and boxing with another
      animal were seen more frequently prior to than after puberty, these behaviors may
      be elements of play fighting (i.e. attack and defense without submission and
      threat). These findings are discussed with respect to the role of gonadal
      hormones in the organization and activation of behavior and with reference to
      their comparative significance in mammals.

PMID- 9177558
TI  - Chronic nicotinic agonist and antagonist effects on T-maze alternation.
AB  - A variety of studies have found that nicotine improves working memory function.
      However, other studies have either not found improvements or have found nicotine
      induced deficits. The demands of the particular memory test may be critical for
      the expression of the nicotine effects. In several studies, we have found that
      chronic nicotine administration improves working memory performance in the radial
      arm maze. Chronic mecamylamine coadministration reversed this effect. The current
      study was conducted to determine the effects of chronic nicotine and mecamylamine
      on choice accuracy in a T-maze spatial alternation task. The same dose and
      duration of nicotine administration that we have previously found to
      significantly improve choice accuracy in the radial-arm maze was not effective in
      altering T-maze spatial alternation. The critical difference in task demands may
      be the presence with T-maze alternation of proactive interference. During a
      session, a choice alternative repeatedly changes valence from correct to
      incorrect and back again. In contrast, with the radial-arm maze as run in our
      studies, in a session the valence of an arm only changes once from correct to
      incorrect. Previous work with nicotine effects on spatial alternation in an
      operant task found evidence that nicotine increased the negative effect of
      proactive interference on performance. In the current study, chronic mecamylamine
      caused a significant deficit in T-maze spatial alternation. This same dose did
      not produce a deficit in the radial-arm maze and, in fact, caused an improvement
      during the first week of administration.

PMID- 9177559
TI  - Nervus terminalis lesions: II. Enhancement of lordosis induced by tactile
      stimulation in the hamster.
AB  - The involvement of the nervus terminalis in lordosis, induced by manual tactile
      stimulation, was investigated in the female hamster. Lordosis latencies were
      measured in response to manual lumbosacral tactile stimulation, which was
      performed at 5 different delay times after the previous lordotic response. Nervus
      terminalis lesion (TNX), control forebrain lesion (FBX), and sham (SH) surgeries
      were performed after preoperative data was collected, and animals were tested
      again postoperatively. Latencies to lordose were compared separately for each
      delay time between preoperative and postoperative tests. The TNX group showed
      small, but significant, decreases in lordosis latencies postoperatively. Lordosis
      latencies for the SH and FBX groups did not change. These results suggest that
      the nervus terminalis plays a minor role in mediating sensory processing during
      reproductive encounters.

PMID- 9177560
TI  - Defect in interleukin-1beta secretion prevents sickness behavior in C3H/HeJ mice.
AB  - To examine the role of interleukin-1beta (IL-1beta) in mediating sickness, we
      studied the effects of lipopolysaccharide (LPS) and IL-1beta on social behavior
      in endotoxin-responsive C3H/HeOuJ (OuJ) mice and endotoxin-resistant C3H/HeJ
      (HeJ) mice. Whereas LPS (1, 10 and 100 microg) depressed social behavior and body
      weight compared to saline in OuJ mice, in HeJ mice it did not. To determine if
      the refractoriness of HeJ mice to the behavioral effects of LPS was related to
      secretion of IL-1beta, in a second study, HeJ and OuJ mice were injected IP with
      LPS (10 microg) and plasma concentration of IL-1beta was determined
      postinjection. At 4 h postinjection, the plasma concentration of IL-1beta was
      increased by LPS in OuJ mice, but not in HeJ mice. The increase in plasma IL
      1beta in OuJ mice corresponded to the maximal depression in social behavior. To
      further verify that HeJ mice are refractory to the behavioral effects of LPS
      because they fail to respond and produce cytokines, the social behavior of HeJ
      and OuJ mice injected IP with recombinant murine IL-1beta (0, 50, 100, or 200 ng)
      was compared. As anticipated, exogenous IL-1beta depressed social behavior
      similarly in endotoxin-responsive OuJ mice and endotoxin-resistant HeJ mice.
      These data indicate that a genetic mutation in HeJ mice that prevents LPS-induced
      synthesis of cytokines also renders HeJ mice refractory to the behavioral effects
      of LPS.

PMID- 9177561
TI  - An automatic food delivery system for operant training of mice.
AB  - We describe an adjustable food delivery system that cuts and delivers calibrated
      pieces of spaghetti to be used as reinforcers to train mice in an appetitive bar
      pressing task. The food delivery is computer-controlled. Uneaten reinforcers are
      detected and removed automatically. One main advantage of this system is the
      ability to adjust reinforcer size to as small as 3 mg. A second advantage is that
      small reinforcers effectively prevent the rapid satiation usually observed with
      commercial products designed for rats, and allow for the expression of high
      behavioral output. Finally, the use of these dustless reinforcers drastically
      reduces the incidence of blockage, a common occurrence with commercial products
      using pellets.

PMID- 9177562
TI  - Histamine release from the hypothalamus induced by gravity change in rats and
      space motion sickness.
AB  - Freely moving rats were exposed to 2 g hypergravity in an animal centrifuge
      device to produce motion sickness. Histamine release from the anterior
      hypothalamus of the rats was measured in vivo with a microdialysis technique.
      After a 2-h load of 2 g hypergravity, rats ate kaolin. Because pica, eating a
      nonnutritive substance such as kaolin, is a behavioral index of motion sickness
      in rats, this finding indicates that the rats suffered from motion sickness.
      During 2 g hypergravity for 2-h, histamine release from the hypothalamus was
      transiently increased. In contrast, neither the transient increase of histamine
      release nor the kaolin consumption were induced by 2 g hypergravity in
      bilaterally labyrinthectomized rats. Pretreatment with alpha
      fluoromethylhistidine, an inhibitor of histamine-synthesizing enzyme, decreased
      both the basal and hypergravity-induced releases of histamine from the
      hypothalamus and suppressed the kaolin consumption induced by hypergravity. Taken
      together, these findings suggest that the vestibular information of changes in
      gravity activate the histaminergic neuron system, resulting in the development of
      motion sickness. More prolonged stimulation, a 4-h load of 2 g hypergravity,
      induced significant increase of kaolin consumption on postdays 1-3, though rats
      ate kaolin on postdays 1-2 after 2 g hypergravity for 2 h. During 2 g
      hypergravity for 4 h, the initial transient increase of histamine release was
      followed by the gradual increase of histamine release after the end of
      centrifugation. It is suggested that rats adapted to the hypergravity environment
      after centrifugation for 4 h, but not 2 h, so that the change in gravity from 2 g
      to 1 g became a provocative stimulation. We, therefore, concluded that motion
      sickness in rats induced by a negative change in gravity can be used as a
      simulation of space motion sickness, which is induced by exposure to
      microgravity. Histaminergic activation in the development of motion sickness
      induced by negative change in gravity might be an underlying mechanism of space
      motion sickness.

PMID- 9177563
TI  - Function of intromissions on intromission-return latency of female rats during
      paced sexual behavior.
AB  - The objectives of this study were to examine how multiple intromissions affect
      the temporal pattern of the female rat's copulatory behavior; in particular, her
      latency to return to the male following intromission (intromission-return
      latency, IRL) and if different hormone replacement regimens affect the temporal
      aspects of female copulatory behavior. Repeated intromissions alone, without
      ejaculation, often resulted in prolonged IRLs equal to the postej aculatory
      refractory period (PER). The first prolonged IRL occurred most frequently between
      the 24th and 44th intromission. The similar pattern of IRLs around the PER and
      the prolonged IRLs may indicate that the mechanisms mediating the occurrence of
      the prolonged IRL are similar to those for the PER. One possible function of the
      prolonged IRLs may be to facilitate the male's ejaculation after the female has
      received enough vaginocervical stimulation for the induction of the
      progestational state of pregnancy. Finally, females receiving a single dose of 50
      microg estradiol benzoate (EB) followed by an injection of 0.5 mg progesterone
      (P) 48 h later showed a significantly longer PER than those receiving 3 daily
      injections of 0.5 microg EB followed by an injection of 0.5 mg P 24 h after the
      last EB injection.

PMID- 9177564
TI  - Immediate early gene expression to examine neuronal activity following acute and
      chronic stressors in rat pups: examination of neurophysiological alterations
      underlying behavioral consequences of prenatal cocaine exposure.
AB  - Altered behavioral responses to stressors have been observed in animals exposed
      to cocaine prenatally. In the present study, both behavioral and physiological
      responses to repeated and single stressor exposure were measured in animals
      prenatally exposed to cocaine. Offspring were derived from 3 prenatal treatment
      groups: dams that were administered 40 mg/kg cocaine from gestational day 8-20
      (C40); dams that were pair-fed and -watered to weight-matched C40 dams (PF); and
      untreated dams (LCC). Starting on postnatal day 16-17 (P16-17), offspring from
      the 3 prenatal treatment groups were exposed to either footshock or isolation
      daily for 5 days. Two days after the last day of stressor exposure (P21-22),
      subjects were given 1 final exposure to the stressor to which they were
      previously exposed. In addition, at P21-22, littermates of animals given repeated
      exposure to stressors were exposed to either footshock or isolation for the first
      and only time. During all footshock sessions, the duration of freezing behavior
      was recorded. Plasma adrenocorticotrophin (ACTH) and corticosterone levels were
      determined from blood samples taken immediately following the final stressor
      session and brains were processed for C-FOS immunoreactivity (FOS-IR). Plasma
      corticosterone was increased following either single or repeated exposure to
      either stressor compared to homecage control animals. Plasma ACTH was increased
      by exposure to both repeated and single footshock exposure, but the increase was
      not as great following repeated footshock exposure, suggesting adaptation to
      repeated exposure to this stressor. Following both single and repeated footshock
      exposure, FOS-IR was increased relative to baseline levels in the paraventricular
      nucleus of the hypothalamus (PVN) and in the supraoptic nucleus (SON), but not
      the locus coeruleus (LC). Repeatedly footshocked animals exhibited more time
      freezing than animals given a single footshock session. Prenatal exposure to
      cocaine resulted in more time spent freezing in C40 than LCC animals during the
      chronic footshock exposure period; however, no differences were seen in any of
      the physiological measures taken from these 2 groups on the final test day. The
      implications of these findings are discussed in the context of other research
      examining the effects of prenatal cocaine exposure on stress responses.

PMID- 9177565
TI  - Short-term odor memory: effects of posterior transection of the lateral olfactory
      tract in the rat.
AB  - Rats were trained on a series of novel 2-odor discrimination problems before and
      after combined unilateral bulbectomy and posterior transection of the
      contralateral lateral olfactory tract. In postoperative tests, experimental rats
      performed as well as controls when a short intertrial interval (30 seconds) was
      used but, in contrast to controls, failed to learn a 2-odor discrimination when
      the intertrial interval was 10 minutes. When tested on a reversal task, controls
      showed memory for original learning by making many errors while experimental rats
      quickly acquired the task. The results suggest that lateral olfactory tract
      afferents to posterior olfactory cortex may play a significant role in short-term
      memory for odors.

PMID- 9177566
TI  - Modulation of behaviour and testosterone concentration in immunodepressed male
      laboratory mice (Mus musculus).
AB  - Recent ideas suggest that current immunocompetence may act as a constraint on
      behavioural and physiological decisions, where these risk imposing an additional
      burden on immune function. We tested this in the context of time budgeting and
      the secretion of the potentially immunodepressive hormones testosterone and
      corticosterone, by treating adult male CFLP laboratory mice with antithymocyte
      serum (ATS) to depress thymus-mediated immune function. In comparison with males
      given a naive rabbit serum (NRS) vehicle control, ATS-treated mice showed a
      reduction in serum testosterone concentration, aggressive behaviour, and general
      activity, and maintained time spent sleeping, relative to pretreatment levels.
      Behaviours that differed between treatments correlated with measures of
      immunodepression (reduction in relative thymus weight or serum total IgG
      concentration), but relationships with behavioural changes were independent of
      those with testosterone. There was little evidence that changes were affected by
      social status. The results are discussed in the context of the adaptive
      modulation of immune function and physiological and behavioural decision-making.

PMID- 9177567
TI  - Adult timing after preweaning shifts of Zeitgeber in rats: crossed sensitization
      to time?
AB  - Preweaning albino rats were exposed from days 1 to 18 of life to successive 6-h
      shifts in light and temperature Zeitgebers, (1-18 rats), whereas controls (C)
      were raised under constant 12:12 L:D and temperature cycles. Cyclic Peak Interval
      performance at adulthood (100 days) showed that 1-18 rats were more accurate and
      sensitive to time than C subjects. These effects, which were akin to a crossed
      senzitization to time, were interpreted within the framework of scalar timing
      theory and the temporal information-processing model. They seemed not to depend
      upon changes in the pacemaker rate (lambda) or the memory constant K*, but to a
      change at the level of the decision process: 1-18 rats used a smaller response
      threshold than controls.

PMID- 9177568
TI  - Physiological responses of red deer (Cervus elaphus) to conditions experienced
      during road transport.
AB  - Remote heart rate and blood sampling devices were attached to transported red
      deer stags to assess the effects of several road transport parameters on
      physiological responses associated with welfare. Stocking density had a
      significant influence on heart rates and plasma lactate concentrations. Heart
      rates of deer transported at a high density (0.38 m2 per 84 kg animal) were 10
      13% higher than those of deer transported at medium (0.62 m2) or low densities
      (0.85 m2). Lactate concentrations of animals transported at a high or medium
      density were 30-40% higher than those of deer transported at a low density. Heart
      rates of deer transported in the back or middle pens were 7-8% higher than those
      of deer transported at the front, and lactate concentrations were 30-40% higher.
      Because elevated heart rates and lactate concentrations are indicative of
      physiological or psychological challenges, it may be best to transport deer at
      densities below the currently recommended limit (0.40 m2/100 kg animal) and to
      keep deer nearer the front of the crate. Although hematocrit, sodium, and
      cortisol concentrations were not sensitive to variation in stocking density or
      the animal's position within the crate, cortisol and sodium concentrations
      increased significantly with time in transit; heart rates and lactate
      concentrations decreased significantly during the journey. A 2-fold increase in
      cortisol during the 2-h trip suggests that the length of journeys should be
      minimized to avoid welfare problems.

PMID- 9177569
TI  - Effect of replacement of fat by nonabsorbable fat (sucrose polyester) in meals or
      snacks as a function of dietary restraint.
AB  - The effect of replacement of fat by nonabsorbable fat on energy intake and on
      feelings of hunger and satiety was assessed, in normal-weight dietary-restrained
      (n = 11), dietary-unrestrained (n = 13) and in postobese dietary-restrained women
      (n = 12), using 2 experimental designs. First, during breakfast and lunch on 2
      sequential weekdays, 23 g of dietary fat was replaced by 23 g of a nonabsorbable
      fat. Second, dietary fat was replaced by a nonabsorbable fat in snacks consumed
      ad lib during a different week. Fat replacement in meals or in snacks did not
      result in changes in hunger and satiety ratings throughout the day. Replacement
      in meals yielded an energy intake reduction of 0.5 MJ/day (not significant) in
      dietary-unrestrained and in postobese dietary-restrained subjects; this reduction
      included 44% energy intake compensation. In normal-weight dietary-restrained
      subjects, energy intake reduction of 0.7 (p < 0.05) MJ/day was observed; this
      reduction included 22% energy intake compensation. Moreover, fat replacement in
      meals showed a shift in macronutrient composition from 35-40% energy from fat to
      31-32% energy from fat. Replacement in snacks yielded an energy intake reduction
      of 0.4-0.5 MJ/day (not significant) in normal-weight dietary-restrained subjects
      and a reduction of 0.6-0.7 (p < 0.05) MJ/day in dietary-unrestrained and in
      postobese dietary-restrained subjects. In this situation, energy intake from
      snacks consisted of 48-78% energy from reduced-fat reduced-energy snacks, which
      implied a replacement of 10-15 g fat by 10-15 g SPE (sucrose polyester) and a
      shift in macronutrient composition from 35-40 percentage energy from fat to 33-36
      percentage energy from fat. These results suggest short-term beneficial effects
      of fat replacement on energy and fat intake.

PMID- 9177570
TI  - Fat perception is related to PROP taster status.
AB  - Individuals who are sensitive to the bitter compounds phenylthiocarbamide (PTC)
      and 6-n-propylthiouracil (PROP) are also more sensitive to selected bitter and
      sweet substances, to sharp-tasting foods, and to the trigeminal irritant
      capsaicin. PTC/PROP tasters have a greater density of fungiform taste papillae
      and it is speculated that PTC/PROP tasters also have more trigeminal innervation.
      Because oral texture perception is also mediated, in part, by trigeminal fibers,
      it has been proposed that individual differences in fat perception might also be
      linked to PTC/PROP taster status and taste bud density. This work tests the
      hypothesis that individuals who are PROP tasters: 1. have a higher density of
      fungiform papillae; 2. are more sensitive to capsaicin; and 3. have increased
      ability to discriminate differences in fat content in salad dressing. Individual
      subjects were classified as PROP nontasters, medium tasters, or supertasters (n =
      25 per group) by comparing their psychophysical function for PROP to that of
      NaCl. Papillae densities (papillae/cm2) were significantly different among the 3
      taster groups (p < or = 0.0001), and were highest among the supertasters. Both
      medium tasters and supertasters perceived more oral burn from capsaicin than did
      nontasters at concentrations of 50, 70, and 100 ppm (p < or = 0.0001). Medium
      tasters and supertasters could also discriminate differences in fat content
      between 40% fat and 10% fat salad dressings (p < or = 0.005), but the nontasters
      could not. These data provide the first published evidence that fat perception
      can be linked to genetic and anatomical differences between individuals.

PMID- 9177571
TI  - Exposure to male siblings facilitates the response to estradiol in sexually naive
      female prairie voles.
AB  - Female prairie voles undergo induced estrus, and require both physical contact
      with males and exposure to male urine to become reproductively active. This study
      attempted to determine if physical contact with males enhanced female response to
      estradiol. Two groups of sexually naive females were tested. One was reared
      without any exposure to males after weaning, and the other was reared with
      sibling males to 60 days of age. Sibling males were used because females avoid
      direct contact with the urine of related males, allowing for the establishment of
      a group of females that experienced physical contact in the relative absence of
      exposure to male pheromones associated with urine. Females were then
      subcutaneously injected with 0.5 microg estradiol benzoate once a day for 7 days.
      Sexual receptivity was tested with novel adult males 48 h and 168 h after the
      first injection. There was a significant difference between the treatment groups,
      with 10% of sexually naive females reared without sibling males displaying
      lordosis compared to 70% of females raised with sibling males. The results
      indicate that exposure to sibling males significantly increased a female's
      behavioral response to estradiol.

PMID- 9177572
TI  - Fractionation and bioassay of human odor types.
AB  - Human urine samples were fractionated to examine the contribution of volatiles to
      the individual body odor. The samples were obtained from 4 male donors and
      fractionated using a vacuum technique. The volatiles from the chemical fractions
      were analyzed using the CLSA technique and gas chromatography. Thereafter, these
      fractions were tested in a computer-controlled olfactometer by trained rats.
      Although the rats were able to discriminate the distillation residue, they could
      not recognize the urine odor in the distilled fraction. The results of gas
      chromatography indicate a continuous release of volatile constituents in the
      distillation residue.

PMID- 9177573
TI  - Application of a radiotelemetry system for chronic measurement of blood pressure,
      heart rate, EEG, and activity in the chicken.
AB  - This paper reports the first successful chronic monitoring (for 30 days) of blood
      pressure, heart rate, EEG, and physical activity in a freely moving bird,
      following (described) implantation of a commercially available (Data Sciences
      International) radiotelemetry device in a 1.6-kg broiler chicken. The tip of the
      device's pressure sensing catheter was introduced into the descending aorta via a
      leg (ischiadic) artery and, although the catheter was tied in place, circulation
      in the leg was maintained and leg function was not impaired. EEG was recorded
      from the device's paired sensing electrodes positioned on the surface of the
      telencephalon. Physiological and activity data collected by the radiotelemetry
      system over 2 complete 24-h periods, 1 and 4 weeks after implantation of the
      device, were analyzed with the system's own (Dataquest LabPRO) analysis software.
      The results presented are discussed mainly in terms of variation between light
      and dark periods.

PMID- 9177574
TI  - A comparative study of clinical and sociocultural aspects of anaemia among
      adolescent girls in rural Ghana.
AB  - This paper presents findings of an exploratory and comparative study of a farming
      and a fishing community of the Ga-Adangme ethnic group in Ghana, which
      investigated the prevalence of malaria and anaemia among adolescent girls (10-19
      years), illness and community perceptions of blood, anaemia and malaria. In both
      communities blood is perceived as the source of life, strength and health of an
      individual. Members of both communities attributed anaemia to poor diet, fevers
      such as malaria, excessive external heat or hard work, flirting and excessive
      worry.

PMID- 9177575
TI  - Evaluation of a simple PCR technique for the diagnosis of Trypanosoma vivax
      infection in the serum of cattle in comparison to parasitological techniques and
      antigen-enzyme-linked immuno sorbent assay.
AB  - Polymerase chain reaction (PCR) with specific oligonucleotides for the
      amplification of Trypanosoma vivax DNA has been developed by Masiga et al. (1992)
      to detect the presence of T. vivax DNA in biting flies. The aim of this
      experiment was to evaluate the efficacy of this technique when applied directly
      on cattle serum, without DNA purification, to detect infection. The sensitivity
      of this PCR technique was compared with parasitological techniques, namely
      haematocrit centrifuge technique (HCT) and buffy coat method (BCM), and with the
      antigen-enzyme-linked immunosorbent assay (Ag-ELISA) for T. vivax developed by
      Nantulya and Lindqvist (1989). Blood and serum samples were collected from four
      calves experimentally infected with a stock of T. vivax from French Guyana
      (IL4007). During the first 51 days of infection, a total of 164 samples were
      collected and processed using the four tests. Mean percentages of positive
      results were 68% with HCT, 59% with BCM, 4% with Ag-ELISA and 64% with PCR.
      Parasitological and PCR techniques yielded approximately the same sensitivities.
      PCR was able to detect active infection in serum samples when parasitaemia was
      over 10(3) trypanosomes/ml. With this isolate of T. vivax the Ag-ELISA was not
      found to be sensitive enough to be used as a diagnostic tool. The sensitivity of
      this PCR technique is not greater than parasitological techniques but it allows
      delayed processing of the samples and gives a highly species-specific diagnosis.
      This simple PCR technique should be evaluated for field diagnosis because it
      makes retrospective epidemiological survey using serum banks possible. Moreover,
      it can be substituted to parasitological techniques when immediate examination is
      not feasible.

PMID- 9177576
TI  - Diversity of Glossina in the forest belt of Cote d'Ivoire.
AB  - Collections of Glossina with a biconical trap have been made for 6 years in the
      forest area of Daloa in Cote d'Ivoire. Three species of Glossina have been
      identified in the village of Bateguedea II as well as in the plantations and
      gallery forests. They are: G. palpalis, G. pallicera and G. nigrofusca. G.
      palpalis was predominant in the village in 1984, representing 74% of the
      collection, while the G. pallicera and G. nigrofusca types are more common in
      plantations and gallery forest. In 1987, 3 years after the first observation, G.
      palpalis was the most common species in each of the three biotopes. G. palpalis
      was even more common in 1990, following a decline in the population of G.
      pallicera and G. nigrofusca in the village (0.2% for G. pallicera; 0.8% for G.
      nigrofusca) and the plantations (0.7% for G. pallicera; 1.3% for G. nigrofusca).
      However, these two species were still found in small numbers in the gallery
      forest.

PMID- 9177577
TI  - Mammal toxicity assessment of the plant molluscicide, Apodytes dimidiata
      (Icacinaceae), in South Africa.
AB  - Apodytes dimidiata has recently come to the fore as a potential plant
      molluscicide for schistosomiasis control in rural communities in South Africa.
      Prior to field applications of its leaves and extract to waterbodies, selected
      acute and sub-acute mammal toxicity tests were conducted in accordance with the
      Organisation of Economic Cooperation and Development (OECD) Guidelines to
      identify any potential hazards that might arise form the plant's use. Acute and
      sub-acute mammal toxicity test results classified A. dimidiata as non-toxic and
      non-irritating. Based on this toxicity evaluation, the dried leaf material and
      aqueous extracts of this plant are considered safe for use in preliminary field
      trials.

PMID- 9177578
TI  - The age-specific prevalence of Plasmodium falciparum in migrants to Irian Jaya is
      not attributable to agglutinating antibody repertoire.
AB  - Previous observations have shown that individuals migrating from a malaria free
      area to a malaria endemic region in North Eastern Irian Jaya quickly acquire anti
      parasite immunity, in an age-dependent manner. Sera from migrants and long-term
      residents in this area were examined for their ability to agglutinate a range of
      Plasmodium falciparum isolates and to disrupt erythrocyte rosettes. Antibody
      responses to merozoite surface protein 2 (MSP2) and ring-infected erythrocyte
      surface antigen (RESA) were also determined. The range of isolates agglutinated
      by sera from the migrants approached that seen in long-term residents. No
      difference was found between migrant adults and children in the range of
      agglutinating antibody, size of agglutinates, nor disruption of rosettes. Anti
      MSP2 and anti-RESA antibodies were the only factors examined which showed a
      correlation with age. We conclude that although antibody to parasite neoantigens
      expressed on the surface of infected erythrocytes may play a role in the
      acquisition of immunity, the humoral response to other P. falciparum antigens is
      more likely to account for the age-dependent prevalence of parasitaemia observed.

PMID- 9177579
TI  - Microsatellite markers for genetic population studies in Glossina palpalis
      (Diptera: Glossinidae).
AB  - Little is known about tsetse intraspecific variability and its consequences on
      vectorial capacity. Since isoenzyme analyses revealed little polymorphism,
      microsatellite markers have been developed for Glossina palpalis gambiensis
      species. Three loci have been identified and showed size polymorphisms for
      insectarium samples. Moreover, amplifications were observed in different species
      belonging to palpalis group. These molecular markers will be useful to estimate
      gene flow within G. p. gambiensis populations and analyses could be extended to
      related species.

PMID- 9177580
TI  - Schistosomiasis infection in relation to the ABO blood groups among school
      children in Zimbabwe.
AB  - The study aimed to establish if there was any relationship between the blood
      group of the human host and schistosomiasis prevalence, intensity, incidence and
      related organ pathology. Urine and stool specimens were collected from the 735
      school children attending a rural school in Zimbabwe to determine the Schistosoma
      haematobium and S. mansoni infection status of the children. The parasitology
      results were used to calculate prevalence and intensity of schistosomiasis
      infection. All the children, irrespective of infection status, were examined for
      signs of organ damage using ultrasonography before those that were infected were
      treated using a single dose of praziquantel. A blood specimen was taken from each
      child for blood group determination. Exactly 1 year later, parasitology was
      repeated to allow calculation of annual incidence of schistosomiasis infection.
      Of the children studied, 212 (28.8%) were of blood group 'A', 156 (21.2%) were of
      blood group 'B' while 367 (49.9%) belonged to blood group 'O'. The prevalence of
      S. haematobium was 59.6% (n = 438) while that of S. mansoni was 15.60% (n = 115).
      S. haematobium infection was detected among 129 (60.8%) children belonging to
      blood group 'A': 225 (61.30%) of blood group 'O' and 84 (53. 80%) of those
      belonging to blood group 'B'. S. mansoni infection was detected among 65 (30.70%)
      blood group 'A' children while 37 (10.10%) blood group 'O' and 13 (8.30%) blood
      group 'B' children were infected. Intensity, annual incidence of S. haematobium
      infection and related organ pathology was significantly higher among children of
      blood group 'A' and lowest among blood group 'O' children (P < 0.01, F-value =
      6.13). Similarly, S. Mansoni intensity and incidence of infection and related
      liver lesions were highest among children of blood group 'A' (P < 0.005, F-value
      = 11.45).

PMID- 9177581
TI  - Physical activity, physical fitness and longevity.
AB  - Numerous studies consistently have shown that higher levels of physical activity
      are associated with decreased risks of coronary heart disease, cerebrovascular
      disease, hypertension, non-insulin-dependent diabetes mellitus, colon and,
      possibly, breast cancer, as well as osteoporosis. The biological processes
      proposed to explain these inverse associations are highly plausible. If physical
      activity does reduce the risk of developing these chronic diseases, we also would
      expect physical activity to delay mortality and enhance longevity. In this
      article, we review the major epidemiological studies worldwide that have examined
      the association between physical activity or physical fitness and all-cause
      mortality. The data from these studies indicate that physical activity is
      effective in postponing mortality and enhancing longevity. Public health
      professionals worldwide should emphasize the need to increase activity levels
      during leisure time, as well as the need to incorporate physical activity into
      the daily activities of life.

PMID- 9177582
TI  - Exercise, free radical generation, and aging.
AB  - Advancing age is associated with profound alterations in body composition and
      exercise capacity. Skeletal muscle mass declines on average of 6% per decade
      after age thirty and this change impacts both basal energy requirements and
      maximal aerobic exercise capacity. While skeletal muscle has one of the highest
      requirements of all tissues for oxygen, exercise increases total oxygen
      consumption by approximately 10-fold, causing an increased rate of production of
      reactive oxygen species (ROS). Biological aging is thought to be influenced by
      ROS generation and older individuals may be more susceptible to exercise-induced
      oxidative damage. However, aging is also associated with increases in antioxidant
      enzymes and controversy still exists as to whether exercise training further
      upregulates the expression of these free radical scavenging enzymes. Older
      individuals who participate in regular exercise may have higher requirements for
      antioxidant vitamins to compensate for the deficit of endogenous antioxidants.

PMID- 9177583
TI  - Apoptosis of skeletal and cardiac muscles and physical exercise.
AB  - Besides the well-known reciprocal influences of skeletal muscle and heart during
      and after physical exercise, a new perspective is emerging on the short- and long
      term effects of exercise-induced damage, in particular the pathogenic role of
      inappropriate apoptosis in skeletal and cardiac muscle. Cells from multicellular
      organisms self-destruct when they are no longer needed, or have become damaged;
      they do this by activating a genetically controlled cell suicide machinery that
      leads to programmed cell death (PCD), or apoptosis. Apoptosis is a specific form
      of programmed cell death that plays an important role in development, growth
      regulation and disease. Skeletal muscles in adult animals are fully
      differentiated syncytial cells. Apoptosis, which is known to be present in
      tissues that modulate their cellular homeostasis under the influence of growth
      and/or hormonal factors, has been recently described in early stages of
      myocardial infarct, and in dystrophic skeletal muscle. The role and the cellular
      and molecular aspects of muscle cell death and apoptosis are far from clear,
      particularly following several types of muscle damage (genetic defects, exercise
      induced damage, oxidative stress, etc.). It can be predicted that apoptosis plays
      a major role in regulating myoblast proliferation during muscle regeneration, and
      in the progression of dystrophinopathies. A particularly important area has
      recently developed concerning cardiac muscle and reperfusion injury after
      ischemia; in this case as well, a major role of apoptosis is emerging.

PMID- 9177584
TI  - Health status of former elite athletes. The Finnish experience.
AB  - Physical activity is an important aspect of health behavior and life-style, when
      considering the possibilities to prevent premature deaths and sustain functional
      capacity. We studied former Finnish male athletes and controls to investigate the
      effects of long-lasting participation in vigorous sports on health, and the main
      findings are reviewed here. The athletes represented Finland between the years
      1920-1965 at least once in international competitions. The following sports were
      selected: track and field athletics, cross-country skiing, soccer, ice hockey,
      basketball, boxing, wrestling, weight lifting, and shooting. The full name, place
      and date of birth were traced for 2613 (97.7%) men. The referent subjects (N =
      1712) were selected among those Finnish men who, at the age of 20, were
      classified completely healthy at the medical examination for induction into
      military service. In most analyses we grouped the sports according to the type of
      training needed to achieve maximal results, i.e., principally aerobic training,
      principally anaerobic training or mixed. In 1985, a questionnaire on physical
      activity, health and health habits was mailed to surviving former athletes and
      referents (N = 2851, 65.9% of the original cohort). Follow-up for morbidity and
      mortality was based on national medical registries. We found that former aerobic
      sports athletes (endurance and mixed sports) in particular have high total and
      active life expectancy and low risk for ischemic heart disease and diabetes in
      later years. On the other hand, they have slightly higher risk for lower-limb
      osteoarthritis. Overall, the benefits of physically active life-style on health
      were clearly higher than the adverse effects.

PMID- 9177585
TI  - Exercise, immunity and aging.
AB  - In general population, many protective immune responses are impaired in old age,
      leading to an increased risk of infection. However, recent studies in SENIEUR
      subjects (healthy centenarians who are examples of successful aging) suggest that
      complex remodeling and reshaping of the immune system occurs with aging. An
      appropriate regular regimen of endurance exercise might help elderly to lead a
      quality of life by preserving immune function. However, very little is known
      regarding the interaction between exercise, aging and the immune system. Given
      that a number of age-related changes occur in many physiological systems which
      are known to alter the immune function both at rest and during exercise, it would
      be of value to learn the extent to which both acute and chronic exercise
      influence immune function in the elderly. The immune system response to exercise
      is multifaceted, depending on the nature of exercise. Significant interaction
      between the neuroendocrine and immune systems, and the role of lifestyle factors
      in immune function are known to occur. In theory, moderate exercise should help
      to reverse the adverse effects of aging upon the immune system by increasing the
      production of endocrine hormones which may contribute to less accumulation of
      autoreactive immune cells by enhancing the programmed cell death. Active elderly
      subjects demonstrated a significantly greater proliferative response to
      phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4)
      production. A moderate training program can enhance the resting natural killer
      (NK) cell function of healthy elderly people, potentially increasing resistance
      to both viral infections and preventing the formation of malignant cells. Recent
      studies have suggested that endurance training in later life is associated with a
      lesser age-related decline in certain aspects of circulating T cell function and
      related cytokine production. It is important that the dose of physical activity
      needed to optimize immune function be defined more clearly at various points
      during the aging process both in females and males in order to optimize the
      immune function and to prevent any rise in adverse effects of exercise on the
      elderly population.

PMID- 9177586
TI  - Aging, fat oxidation and exercise.
AB  - Aging is characterized by deleterious changes in body composition and in fat
      distribution. The mechanisms that determine the aging-associated changes in body
      composition are not well defined, but the evidence suggests that the loss of fat
      free mass is at least partially attributable to physical inactivity. The increase
      in fat mass may be the result of alterations in fatty acid metabolism. Indeed,
      fat oxidation is decreased in elderly individuals in several physiological
      conditions: a) at rest, b) during exercise, and c) in response to meal ingestion
      (after weight loss). These defects are related in part to loss of fat-free mass,
      but may also be the consequence of estrogen loss (in women) and/or a decrease in
      the intrinsic capacity of muscle for fat oxidation, and are amenable to partial
      correction by exercise training. Special emphasis should be placed in future
      studies upon the role of steroid hormone in the regulation of fatty acid
      metabolism in elderly individuals (especially women), as well as therapeutic
      interventions that may increase the quantity of the fat-free mass and/or fat
      oxidation.

PMID- 9177587
TI  - Influence of physical exercise on old rats: changes in patterns of spontaneous
      activity and connective tissues.
AB  - It has been shown that life-long, regular physical exercise has benefits for
      humans as well as laboratory animals. Population studies have shown that the
      longevity of humans is increased due to the decrease in all-cause mortality.
      Further, the functional capacities of organ systems, especially the
      cardiovascular, are maintained better. Body fat content stays lower. Similar
      conclusions have been drawn from animal studies, most of them using voluntary
      exercise in running wheels. We have previously shown that spontaneous activity,
      measured in an open field setting, is better preserved, suggesting a slowing of
      sensorimotor impairment with age, and possibly improved maintenance of
      dopaminergic and cholinergic systems. Further, the systemic effect on connective
      tissues was a slowing of the age-dependent increase of stability by changes in
      the cross-linking patterns. The purpose of the present investigation was to
      analyze whether late-onset training programs had any such effects, i.e., whether
      the aging effects seen in sedentary animals could be reversed to some extent. We
      trained male Sprague-Dawley rats from the age of 18 and 20 months until the age
      of 22 months, i.e., for 4 and 2 months, in a treadmill for 800 m/day. Spontaneous
      activity in an open field was assessed at the ages of 18, 20, and 22 months. For
      systemic changes in connective tissues, tail tendons were analyzed with respect
      to thermal stability and biomechanical strength parameters. The rats trained for
      4 months lost weight significantly, which suggests that most of the fat
      accumulated during a sedentary life can be removed by physical exercise. Two
      months of training, either from the age of 18 or 20 months, had a positive effect
      on spontaneous activity, while the last 2 months of a 4-month training period had
      a negative influence. We conclude that the exercise program was too strenuous to
      be maintained for 4 months, which should be interpreted as a failure to increase
      the functional capacity sufficiently. Analysis of the thermal stability and
      biomechanical properties showed that both training programs moved these
      properties in a "younger" direction. We conclude that training starting late in
      life also influences the aging rat in a positive way, although there are
      limitations to the intensity of training that is beneficial.

PMID- 9177588
TI  - Physical activity as a factor in the action of dietary restriction on aging:
      effects in Fischer 344 rats.
AB  - Dietary restriction (DR) slows the rate of aging in laboratory rodents but the
      mechanism of action is unknown. DR is known to induce beneficial effects in a
      variety of tissues and organ systems. DR also maintains high levels of physical
      activity over the life span. We tested the hypothesis that lifelong physical
      activity is an important component of the anti-aging action of DR. Male specific
      pathogen-free Fischer 344 rats were divided into 4 groups at 6 weeks of age: A:
      fed old libitum; AE: fed ad libitum and in cages with running wheels; B: fed 60%
      ad libitum; BE: fed 60% ad libitum and in cages with running wheels. Running
      activity and spontaneous cage activity were measured over 24 hours and over the
      life span. Metabolic rate was measured indirectly by analysis of air entering and
      leaving cages. AE rats exhibited low levels of running activity and ran very
      little beyond 6 months of age. In contrast, BE rats sustained high running levels
      even after all A and AE rats had died. High levels of wheel running did not
      decrease spontaneous cage activity. Median life span (50% survival) was in the
      order A = AE < B < BE. Ten percent survival was in the order A = AE < B = BE. BE
      rats had greatest median life span and also highest specific metabolic rate.
      Exercise and DR altered pathology: At death BE rats had a high incidence of
      cardiomyopathy, whereas A and AE rats had high incidence of chronic nephropathy
      and pituitary tumors. The data indicate that increased physical activity is
      probably not an important factor in the action of DR on aging.

PMID- 9177589
TI  - Life-long endurance-trained elderly men have high aerobic power, but have similar
      muscle strength to non-active elderly men.
AB  - The knee extensor and plantar flexor muscle groups of elderly men (age 70-100
      years, N = 15), who since adolescence had maintained an extremely high level of
      endurance-based physical activity (maximal oxygen uptake 41.9 +/- 4.8 mL.kg-1min
      1 in subjects < 80 years, (N = 8) and 27.1 +/- 5.4 mL.kg-1min-1 in those > 80
      years, N = 5), were compared in terms of maximum voluntary isometric strength and
      twitch contractile properties with the muscles of elderly men of a similar age
      who did not undertake any regular physical exercise (68-92 years, N = 18) and of
      young control subjects who were recreationally active (21-36 years, N = 17). No
      difference was observed in the maximum voluntary strength of the knee extensors
      (338 +/- 130 N vs 341 +/- 137 N) or plantar flexor muscle groups (106 +/- 24 Nm
      vs 115 +/- 46 Nm) between the endurance-trained and elderly control subjects.
      This was still the case when the subjects were divided into those above and below
      80 years of age, or when the data were expressed relative to body weight. Both
      groups of elderly subjects were markedly weaker than the young control subjects.
      In the plantar flexors, twitch time to peak tension (TPT) was significantly (p <
      0.05) prolonged in both groups of elderly subjects vs the young control subjects.
      In the knee extensors, however, TPT was only prolonged in the endurance-trained
      athletes. Half relaxation time was prolonged in the knee extensors of both groups
      of elderly subjects, but only prolonged in the plantar flexors of the control
      subjects. The data raise the question of specificity of muscle usage, and its
      effect on skeletal muscle function, and suggest that endurance-based physical
      exercise may be of little value in maintaining muscle strength and speed of
      contraction in old age.

PMID- 9177590
TI  - Relationship of body composition and cardiovascular fitness to lipoprotein lipid
      profiles in master athletes and sedentary men.
AB  - A number of studies demonstrate that highly conditioned older athletes are leaner
      than their sedentary counterparts, and have lipoprotein profiles similar to that
      of young individuals. It is not clear whether the high maximal aerobic capacity
      (VO2max) or lean body habitus is the major determinant of the favorable
      lipoprotein lipid profiles present in older athletes. The objective of this study
      was to determine whether body composition or VO2max was the major determinant of
      lipoprotein lipid profiles among 61 master (age 63 +/- 6 years, mean +/- SD)
      athletes (VO2max > 40 mL/kg/min), 39 age-matched lean (% body fat < 25%), and 51
      obese (% body fat > 25%) sedentary men. Plasma high density lipoprotein
      cholesterol (HDL-C) concentrations were 25% higher in that athletes than in the
      lean sedentary men, and 42% higher than in the obese sedentary men. Triglyceride
      (TG) concentrations were 24% lower in the master athletes than in the lean
      sedentary men, and 51% lower than in the obese sedentary group. Plasma low
      density lipoprotein cholesterol (LDL-C) levels were 9% lower in the athletes than
      in the other groups of sedentary individuals. In stepwise multiple regression
      analysis the percent body fat was the major independent predictor of HDL-C and TG
      levels accounting for 29% and 41% of the variation in these levels, respectively.
      The VO2max accounted for an additional 6% of the variance in HDL-C levels and 2%
      of the variance in TG levels. These cross-sectional results suggest that the
      favorable lipoprotein profile of master athletes is largely due to their lean
      body habitus, with a small independent contribution from their higher levels of
      cardiovascular fitness. Thus, regular vigorous aerobic exercise and maintenance
      of low body fat may prevent the commonly observed age-associated deterioration in
      lipoprotein concentrations.

PMID- 9177591
TI  - One-leg standing balance and functional status in a population of 512 community
      living elderly persons.
AB  - The objective of this cross-sectional study (whose baseline data were drawn from
      a longitudinal population study) was to determine if one-leg standing balance
      might be a useful marker of functional status in elderly persons independently
      living in an urban community (N = 512, mean age 73 +/- 7.0, 71.4% women). One-leg
      standing balance (ascertained by the Tinetti test) and functional status were
      obtained from a baseline gerontological assessment and follow-up questionnaires.
      Correlations were tested between one-leg balance and physical health and
      functional measurements. One-leg standing balance (OLSB) was abnormal in 24.7% of
      the population. At least one incapacity in instrumental activities of daily
      living (IADL) was found in 60.6% of those with OLSB abnormality, vs 45.5% in
      those with OLSB "adaptive" (borderline abnormal), and 33.3% in those with normal
      one-leg standing balance (p < 0.0001). Multivariate analysis showed 3 independent
      factors related to one-leg balance abnormality: age > 71 years (OR = 5.11, CI =
      1.99-13.10); IADL deficit requiring help with transportation (OR = 3.61; CI =
      1.15-11.40); and "poor" health status on the Iowa Self-Assessment Inventory (OR =
      2.67, CI = 1.35-5.27). We conclude that one-leg standing balance may be a simple,
      predictive and inexpensive marker helpful in screening for low functional level
      and frailty in clinical practice.

PMID- 9177592
TI  - A randomized trial of walking versus physical methods for chronic pain
      management.
AB  - We conducted a pilot study to evaluate a practical exercise program for elderly
      people with chronic musculo-skeletal pain. Thirty-three subjects (mean age, 73
      years; 69% back pain; 24% knee pain; 9% hip pain) were randomly assigned to one
      of three groups. Group 1 received 6-week supervised program of walking. Group 2
      received a pain education program that included instruction and demonstration of
      use of heat, cold, massage, relaxation and distraction. Group 3 received usual
      care. Outcomes including pain, self-reported health and functional status, and
      performance-based measures of functional status were evaluated at baseline, at
      two weeks and at eight weeks (end of study). Attendance was 100% for the
      education sessions and 93% for walking sessions. No injuries were sustained. Both
      intervention groups demonstrated significant improvements in pain (p < 0.05) and
      performance-based measures of functional status (p < 0.05), while the control
      group had no changes. These data suggest that patient education and fitness
      walking can improve overall pain management and related functional limitations
      among elderly people with chronic musculo-skeletal pain.

PMID- 9177593
TI  - Muscle function of women aged 65-89 years meeting two sets of health criteria.
AB  - This study compared the isometric strength, leg extensor power, and some
      potentially related functional abilities of elderly women selected for exercise
      studies according to two sets of readily applicable exclusion criteria. The
      health status criteria ("healthy" and "medically stable") differed principally in
      respect to duration of freedom from diagnosed or symptomatic disease, medication
      taken and Body Mass Index. Fifty "healthy" women and fifty "medically stable"
      women, aged 65 to 89 and evenly distributed over the age range, were recruited
      through local and national newspapers. There was no significant difference
      between the two health groups in strength or power. However, the women in the
      "medically stable" group were heavier and had more difficulty in rising from a
      chair. The strength of the relationships between strength, power and kneel rise
      time were very dependent on body weight for the "medically stable" women but not
      for the "healthy" women. The health criteria used to classify elderly subjects
      must be clearly specified so that there may be easier interpretation of results
      from future studies. This is especially true in studies where body weight might
      be important.

PMID- 9177594
TI  - A comparison of the effects of three types of endurance training on balance and
      other fall risk factors in older adults.
AB  - We hypothesized that short-term endurance training improves balance in older
      adults, if training involves movements that "stress" balance. We tested the
      hypothesis by looking for a dose-response relationship between movement during
      exercise and balance improvement. The study was a single-blinded, randomized
      controlled trial. Subjects were sedentary adults (N = 106) aged 68-85 with at
      least mild deficits in balance. Exercise groups were: stationary cycle (low
      movement), walking (medium movement), and aerobic movement (high movement).
      Subjects attended supervised exercise classes three times a week for three
      months, followed by self-directed exercise of any type for three months. The
      primary test of the hypothesis compared changes in balance after three months of
      supervised exercise. One balance measure (distance walked on a six-meter narrow
      balance beam) improved in the hypothesized dose-response manner (cycle, 3%
      improvement; walking, 7% improvement; aerobic movement, 18% improvement: p <
      0.02, test of trend). Other balance measures did not improve with exercise. Only
      walking exercise improved gait speed (by 5%, p < 0.02) and SF-36 role-physical
      score (by 24%, p < 0.05). VO2max improved with walking (18%, p < 0.004) and
      aerobic movement (10%, p < 0.01), but improved less with cycling (8%, p > 0.1).
      Leg strength improved significantly in all exercise groups. The study hypothesis
      was supported only for one balance measure. Only walking improved at least one
      measure of all major outcomes (endurance, strength, gait, balance, and health
      status), suggesting that walking is most useful for all prevention. Cycle
      exercise appeared least useful.

PMID- 9177595
TI  - Do echocardiographic changes explain the age-associated increase in exercise
      induced supraventricular arrhythmias?
AB  - Although exercise-induced supraventricular arrhythmias (EISVA) increase with
      advancing age, it is unclear whether age-associated changes in cardiac structure
      or function play a major role in this increase. To address this question, we
      examined the relationship between M-mode echocardiographic variables and EISVA
      occurring during maximal treadmill exercise in 366 healthy volunteers aged 20 to
      90 years from the Baltimore Longitudinal Study of Aging. Simple (i.e., isolated)
      EISVA were detected in 69 subjects (19%), and complex EISVA (i.e., comprising >
      10% of beats in any minute or occurring in runs) in another 29 subjects (8%).
      Univariate predictors of any EISVA, whether simple or complex, were older age (p
      < 0.0001), male gender (p < 0.05), greater left atrial size (p < 0.01), left
      ventricular mass index (p < 0.0001), interventricular septal thickness (p <
      0.001), isovolumic relaxation time (p < 0.01), atrial filling fraction (p <
      0.01), reduced mitral E-F closure slope (p < 0.001), peak E velocity (p < 0.02),
      and peak E/A ratio (p < 0.0001). Lesser exercise duration (p < 0.01), lower
      maximal heart rate (p < 0.0001), and higher peak systolic and diastolic blood
      pressures (p < 0.001) were also associated with EISVA. However, by multiple
      logistic regression analysis, age (p < 0.0001) was the only independent predictor
      of any EISVA. Univariate predictors of complex EISVA were greater age (p <
      0.0001), and atrial filling fraction (p < 0.001), diastolic blood pressure (p <
      0.05), lesser mitral E-F slope (p < 0.004), exercise duration (p < 0.005) and
      maximal heart rate (p < 0.01). However, only age (p < 0.0001) independently
      predicted complex EISVA. Thus, in healthy volunteers undergoing maximal treadmill
      exercise. EISVA are associated with greater left ventricular wall thickness,
      reduced early diastolic performance, diminished exercise capacity and elevated
      exercise blood pressure. However, none of these variables are independent
      predictors of EISVA over and above the powerful effect of age.

PMID- 9177596
TI  - The reliability and validity of an obstacle course as a measure of gait and
      balance in older adults.
AB  - The use of an obstacle course to quantify gait, balance and functional mobility
      in elderly persons, particularly to assess objectively changes following exercise
      and rehabilitation interventions, has not been extensively developed or tested.
      In this study, we describe an 18-item obstacle course developed as an outcome
      measure for an exercise intervention among fall-prone elderly men. Reliability
      and validity of the obstacle course was tested in a group of 58 community-living
      elderly men (mean age = 75 years). Each subject's performance was videotaped and
      timed. The videotapes were scored by a physical therapist and a physician. Inter
      rater reliability between the raters was high (Kappa = 0.96, p < 0.0001). Both
      the obstacle course score and time correlated significantly with gait velocity, a
      6-minute walk test, and a performance-oriented instrument of gait and balance.
      Obstacle course scores showed significant improvement among the most impaired
      subjects, but not among higher functioning subjects following a 3-month exercise
      intervention. These results suggest that an obstacle course may be a useful and
      valid method for measuring outcomes related to mobility tasks in selected elderly
      populations. Further work is needed to determine in which populations, and for
      which outcomes, an obstacle course is better than simpler performance-based
      measures.

PMID- 9177597
TI  - Mood, physical working capacity and cognitive performance in the elderly as
      related to physical activity.
AB  - The age-related decline in physical working capacity, cognitive performance, and
      psychological well-being can presumably be modified by regular physical exercise.
      The present study comprises 20 men and 20 women with a mean age of 66 years. Half
      of the participants were randomly assigned to an exercise group, the remaining
      half to a control group. The members of the exercise group exercised individually
      through regular walking (three times a week) during a period of three months. The
      control group performed instead a series of mental tasks with the same
      regularity. Results showed significant differences in favor of the exercise group
      on complex tasks at the post-test, whereas only minor differences were found on
      simple tasks. Mood improvements were uniform, regardless of exercise involvement.
      The latter can be taken to indicate that exercise is not the most important
      factor, instead social context and regular contacts with other people may be
      equally important for elderly individuals.

PMID- 9177598
TI  - Predictors of five-year functional ability in a longitudinal survey of men and
      women aged 75 to 80. The 1914-population in Glostrup, Denmark.
AB  - Data from a longitudinal study of aging-a Danish substudy within a Nordic
      comparative longitudinal Research on Ageing study (NORA)-is presented. The goal
      is to highlight easily measured factors, that are relevant to prevention and
      postponement of disability in the elderly. In a population-based, representative
      sample, the objectives were: to describe five-year outcome regarding death and
      functional ability to age 75 to 80, as well as individual changes in muscle
      strength, physical performance in simple function tests and self-reported
      physical activity, and relate "risk markers" to five-year outcome. Baseline
      values were obtained in 405 participants in the 1989-survey of the 1914-cohort in
      Copenhagen County. The 307 survivors were invited for the survey of 80-year olds
      in 1995. Outcome was measured as death, non-participation, decline, stability or
      improvement in two measures of mobility function (tiredness and dependency).
      Between ages 75 and 80, 24% died, 12% did not participate in the follow-up, 23%
      became tired performing mobility functions, 20% did not change but 21% became
      less tired; 19% became more dependent, 44% remained stable and only 2% improved
      in relation to dependency on help in mobility functions. "Stability" in mobility
      functions was related to ability to mount stairs, walking speed, mood and
      physical activity. Number of chronic diseases and low pulmonary function were
      only related to mobility in men. Among people who improved their function, many
      had rather low baseline-values, suggesting regression to the mean. Multiple
      logistic regression was conducted. The follow-up survey found that female
      participants were more physically active at baseline than non-participants. Five
      year mortality was independently related to physical activity (RR = 0.41),
      pulmonary function in men (RR = 0.45/l increase) and muscle strength in women (RR
      = 0.65/N/kg increase). Dependency at follow-up in men was related to low physical
      activity at baseline (RR = 4.14), disability to mount a 50-cm step (RR = 4.07),
      two or more chronic diseases (RR = 3.36) and, only marginally significant, knee
      extension strength. In women only low physical activity was predictive (RR =
      4.32). From baseline to follow-up, 34% of the population had reduced their
      physical activities. Knee extension strength was reduced from 6.0 to 4.4 N/kg in
      men, and from 4.2 to 3.3 N/kg in women. In the stair-mounting test, 44% could
      only attain one or more 10 cm steps lower than at baseline. A dose-response
      relationship of declining muscle mass to functional limitations was observed in
      men and women at the age of 75 as well as the age of 80.

PMID- 9177599
TI  - Uncoupling of changes in skeletal muscle beta-adrenergic receptor density and
      aerobic capacity during the aging process.
AB  - The results of the present study indicate that the density of the beta-adrenergic
      receptors in the skeletal muscle does not decline with age, despite declines in
      oxidative capacity both in the skeletal muscle and whole body oxygen consumption.
      When young rats and old rats of equal body weight trained daily at the same
      duration and speed for 6 months on the treadmill, skeletal muscle of young and
      old rats reached the same aerobic capacity. The young demonstrated a significant
      rise in Bmax of the beta receptors, while the old rats did not change their
      density of receptors. When both young and old rats had the contractile activity
      of their skeletal muscle raised to the same level through chronic tonic
      electrical stimulation, the aerobic-capacity and beta receptor density rose to
      the same levels in the skeletal muscle. Thus, the contraction-dependent pathway
      in the senescent muscle appears to function normally given a maximal chronic
      stimulus via electrical stimulation. These data indicate that the relationship
      between oxidative capacity, beta-adrenergic receptor properties, exercise
      training, and aging does not appear to be readily explicable by a single unifying
      mechanism, but probably resides in the interaction of age with a differential
      responsiveness of the beta-adrenergic and/or contraction dependent pathway for
      stimulation of aerobic capacity in the aging skeletal muscle.

PMID- 9177600
TI  - Antisignature oligonucleotides and their analogs as inhibitors of mollicutes
      cofactors of HIV.
AB  - Inhibition of mollicutes by synthetic oligonucleotides and their analogs
      complementary to specific "signature" regions of 16S rRNA and corresponding
      sequences of ribosomal operon DNA was studied. It was shown that antisignature
      oligonucleotides inhibited transcription in vitro for above 79% interacting
      specifically with ribosomal operon and non-specific with DNA-dependent RNA
      polymerase. The inhibition efficiency depended on oligonucleotide sequence and
      type of modification. Translation in vitro was suppressed most efficiently (up to
      60%) by oligonucleotides complementary to 3'-end region of 16S rRNA, also
      depending on their modification. Translation in vivo was inhibited most
      efficiently (up to 73%) by thiophosphate analogs of oligonucleotides
      complementary to sequences 499-507 and 523-532 of 16S rRNA responsible for
      binding of ribosomal "core" protein S4 starting the assembly of 30S ribosome
      subunit. With the simultaneous use of the last two oligonucleotides, the growth
      of mollicutes in SM IMV-72 medium rich in exogenous sources of nucleosides was
      suppressed for over 90%. It is supposed that under conditions where mollicutes
      have no free access to starting materials for their own synthesis of nucleic acid
      these nucleotides could suppress microorganisms completely. Antisignature
      oligonucleotides are considered as superspecific agents not leading to the
      development of resistance of mollicutes and believed to be the main future remedy
      against diseased caused by microorganisms lacking the system of nucleoside
      synthesis.

PMID- 9177601
TI  - Heat-shock-proteins-antibodies in patients with Helicobacter pylori associated
      chronic gastritis.
AB  - Twenty eight patients (15 F, 13 M mean age 37.7 SD +/- 9.93 range 22-55) affected
      by Helicobacter Pylori infection associated gastritis were studied. HSP 70
      Antibodies were found in 21.4% of patients and their mean values were
      significantly higher in the patients than in the subjects affected by gastritis
      HP negative used as controls (p = 0.05). This datum was confirmed by Western
      blotting. The presence of HSP 70 antibodies in the sera of those patients may
      support the link between the protein and the development and persistence of
      chronic inflammation in the gastric mucosa.

PMID- 9177602
TI  - Infectious arterial aneurysms: patterns and treatment.
AB  - PURPOSE: To evaluate patterns and evolution of treatment of infectious arterial
      aneurysms in a 15 year period. MATERIAL AND METHOD: Eight patients bearing 8
      arterial aneurysms: 4 aorto-iliac, 1 of the internal carotid, 1 of the posterior
      tibial, 1 of the cubital, 1 of the internal carotid artery. For the aorto-iliac
      aneurysms treatment consisted in resection extra-anatomic by-pass in 2, "in situ"
      prosthetic grafting in the other 2. Extra-abdominal aneurysms were treated by
      excision/"in situ" vein grafting in two cases and simple resection in other two
      cases. RESULTS: One post-operative death occurred, due to rupture of a ligated
      aortic stump. No death or major complication occurred after "in situ" treatment
      of aorto-iliac aneurysms and, overall, in extra-aortic aneurysms. CONCLUSIONS:
      Staphylococcus and miceti have become the most frequently encountered causative
      agents. "In situ" grafting together with aggressive antibiotic therapy became the
      preferred method in the recent years and yielded good results.

PMID- 9177603
TI  - Serum osteocalcin levels in postmenopausal obese women.
AB  - In epidemiology of osteoporosis, obesity is to be considered one of its
      protecting factors. However there are in the literature discordant opinions: some
      authors describe a protective effect of obesity on the trabecular bone, others on
      the cortical one, others no effects at all and others finally a positive
      influence on both the trabecular and the cortical bone. However, only few studies
      on obesity's impact on bone metabolism are available. Bone mineral density at
      forearm and serum osteocalcin levels, a specific and sensitive marker of bone
      turn-over, in a group of postmenopausal obese women with those of a nonobese
      control group were compared. Obese women showed higher densitometric measurements
      than nonobese, but only the values of the third distal site of forearm resulted
      higher in a significant way. Serum osteocalcin values were similar between the
      two groups but the obese women showed a greater dispersion of the values (8.15 +/
      4.96 ng/ml) compared to nonobese (8.35 +/- 1.63 ng/ml). This high variability
      suggests an heterogeneity of bone turn-over in obese subjects and could explain
      the discordant results of the literature.

PMID- 9177604
TI  - Advanced cervical pregnancy.

PMID- 9177605
TI  - Circadian rhythm of serum erythropoietin in healthy subjects.
AB  - BACKGROUND: The diurnal rhythm in the circulating serum levels of erythropoietin
      (EPO) was investigated in healthy subjects. METHODS: Venous blood samples were
      drawn during the span of a whole day every four hours, starting from midnight,
      for the determination of serum Epo levels by RIA in 40 clinically healthy
      normocytemic subjects, 27 males and 13 females, aged 30-75 years. Statistical
      analysis was carried out by means of the "cosinor" method. RESULTS: Serum EPO
      presents a significant (p < 0.05) circadian rhythm with higher levels in the
      afternoon and lower levels in the nightime. CONCLUSIONS: These data confirm the
      presence of a circadian rhythm in serum EPO levels. The mechanisms behind the
      circadian rhythmicity are still unknown. For clinical evaluation of the serum EPO
      values, the time of day for collection of blood samples has to be taken into
      consideration.

PMID- 9177606
TI  - Hypertension and CHD: evidence of glucose and lipid metabolism involvement.
AB  - Three hundred and seventy subjects (217 women and 153 men) affected by essential
      hypertension of moderate or severe degree were studied. Their age ranged from 28
      to 57 years, with a mean of 47 years. 251 patients had a normal electrocardiogram
      (ECG) and 119 patients an abnormal ECG: 78 with T wave abnormalities, 4 with Q-S
      segment abnormalities, 9 with left bundle branch block and 28 with left
      ventricular hypertrophy. Control group was composed by 45 non hypertensive
      subjects matched for age and sex. Glucose and insulin concentrations, before and
      after the oral glucose intake, were higher in patients with essential
      hypertension than in control group. The hypertensive patients with abnormal ECG
      were found to have higher plasma insulin response, high triglyceride plasma
      levels, total cholesterol and LDL cholesterol concentrations, associated with a
      significant increase in the total cholesterol/HDL cholesterol ratio.

PMID- 9177607
TI  - Circulating levels of intercellular adhesion molecule-1 (ICAM-1) and soluble
      interleukin 2 receptors (IL-2R) in patients with B cell chronic lymphocytic
      leukaemia.
AB  - The serum concentrations of circulating ICAM-1 (cICAM-1) and soluble receptors
      for interleukin-2 (sIL-2R) were evaluated on 48 patients with B-cell chronic
      lymphocytic leukaemia (B-CLL) and on 15 healthy control subjects. The mean +/- SD
      concentration of cICAM-1 was significantly higher (p < 0.002) in B-CLL patients
      (407.7 +/- 164.3 ng/ml) than in healthy controls (245.4 +/- 76.7 ng/ml). Patients
      with progressive disease had higher cICAM-1 levels than patients with "indolent"
      disease (440.38 +/- 32.3 ng/ml versus 321.36 +/- 14.45 ng/ml; p < 0.0001). Serum
      levels of cICAM-1 were also significantly higher (p < 0.0002) in patients with
      advanced stage (III-IV) than in those with early stage (I-II). The increase of
      cICAM-1 levels was positively correlated to increases of soluble receptors for
      interleukin-2 (r = 0.9; p < 0.0001). These results seem to show that the
      measurement of serum levels of cICAM-1 may be an useful tool for monitoring
      disease activity and tumoral mass in patients with B-CLL. However, further
      studies are needed to define the functional role of high cICAM-1 levels in the
      immunological dysregulation of patients with malignancy.

PMID- 9177608
TI  - Acute pseudo-obstruction of the colon: a clinical contribution and review of the
      literature.
AB  - Acute idiopathic pseudo-obstruction of the colon, or Ogilvie's syndrome, is a
      rather unfrequent condition. Although it has been associated to a variety of
      pathological conditions, the etiology is still unknown. The authors refer upon a
      case of Ogilvie's syndrome observed by them and, confronting the data that
      emerged reviewing the literature with their experience, they retain that if the
      conservative therapy fails, and in absence of perforations or ischemic lesions,
      the treatment to prefer is the positioning of a cecostomy tube in local
      anesthesia. For elderly patients with unsufficiently good general conditions who
      present a recurrent acute pseudo-obstruction of the colon, it is advisable to
      confection a definitive cecostomy.

PMID- 9177609
TI  - Serum alpha 2-macroglobulin levels in psoriatic patients treated with UVB and
      PUVA.
AB  - BACKGROUND: Abnormalities in proteinase metabolisms have been found in psoriasis
      and higher concentrations of neutral proteinases in psoriatic skin lesions than
      in unaffected skin of psoriatic patients have been observed. AIM: The aim of the
      study was to determine whether repeated whole body UV-(UVB and PUVA) irradiation
      is associated with changes in proteinase inhibitor alpha 2-macroglobulin (alpha 2
      M) in patients with active plaque psoriasis. PATIENTS AND METHODS: In this study,
      the sera alpha 2-M levels were evaluated in cases of active plaque psoriasis
      before UV-, four weeks UVB (15 patients) and PUVA (11 patients) irradiation, and
      two weeks after completed treatment. RESULTS: Both UVB and PUVA treatment had no
      significant influence on alpha 2-M levels in psoriatic sera, it was, however,
      sufficient to treat most of the skin lesions. DISCUSSION: The beneficial effect
      of phototherapy in psoriasis seems not to be mediated through increased binding
      of proteinases by proteinases inhibitor alpha 2-M from serum.

PMID- 9177610
TI  - High prevalence of asymptomatic hypothyroidism and hyperthyroidism in
      hospitalized elderly females.
AB  - To investigate the prevalence of asymptomatic hypothyroidism and hyperthyroidism
      in hospitalized people, we performed thyroid function tests on a group of 2545
      elderly patients consecutively observed in a General Hospital in Rome, during a
      six year period. The rate of asymptomatic hypothyroidism was as high as 0.71% in
      female patients and only 0.20% in male patients. In asymptomatic hyperthyroid
      subjects the prevalence rate was 0.58% in females and 0.20% in males. On the
      whole, prevalence rate of asymptomatic thyropathies resulted 0.94%, showing a
      clear difference in sex (women 1.29% and men 0.40%). The asymptomatic
      thyropathies screening of hospitalized elderly women may result in a very low
      cost diagnosis of many new cases of hypothyroidism and hyperthyroidism.

PMID- 9177611
TI  - The atrial natriuretic peptide-renin-aldosterone system in hepatorenal syndrome.
AB  - BACKGROUND: Hepatorenal syndrome (HRS) is a functional acute renal failure
      occurring in patients with advanced liver disease: the etiology of HRS is still
      unknown, but a role in its development and maintaining is played by the atrial
      natriuretic peptide-renin-aldosterone system. Aim of the study was to investigate
      the circulating plasma levels of the atrial natriuretic peptide (pANP), plasma
      renin activity (PRA) and plasma aldosterone (pA) in a group of HRS patients,
      compared to healthy controls. METHODS: Venous blood samples were drawn at 8:00 am
      in 36 healthy controls and in 20 patients with HRS following liver cirrhosis for
      the radioimmunoassay measurement of the circulating pANP, PRA and pA levels. The
      mean values of each variable were compared between the two groups by the "t"
      test; linear regression analysis was used to correlate the values of pANP and
      PRA, pANP and pA, and PRA and pA in the two groups. RESULTS: HRS patient
      presented significant (p < 0.05) higher levels of pANP, PRA and pA than controls.
      Significant (p < 0.001) relations were found in healthy subjects between pANP and
      PRA (r = -0.78), pANP and pA (r = -0.68), and PRA and pA (r = 0.71), whereas the
      HRS group have only a significant (p < 0.001) positive relation between pANP and
      PRA (r = 0.67). CONCLUSIONS: These data indicate that HRS is not due to a
      deficiency in circulating pANP. The elevated pANP levels in HRS may suggest a
      renal insensitivity to its natriuretic effects, and the derangement in the
      relationships and function in the atrial natriuretic peptide-renin-aldosterone
      system could be considered an important pathophysiologic mechanism in the hydro
      electrolyte unbalance of HRS.

PMID- 9177613
TI  - Hypertension and menopausal syndrome: effects of hormone replacement therapy and
      antihypertensive drugs.
AB  - Arterial hypertension is a common finding in climacteric women even though the
      role of reduced estrogen levels in promoting this condition remains unclear. The
      purpose of the present survey was to evaluate the effects of hormone replacement
      therapy in hypertensive postmenopausal women. 180 patients were studied; they had
      been postmenopausal for 12-18 months and afflicted with mild or moderate
      essential arterial hypertension for less than 2 years. Patients were randomly
      divided into two groups and treated with progestin-estrogen therapy (group I, 96
      patients) or with antihypertensive drugs (group II, 84 patients). Fourty-one
      cases in group I (42.7%) responded adequately to hormone therapy with persistent
      normalization of blood pressure levels; antihypertensive drugs were effective in
      61 patients in group II (72.5%). The 23 unresponsive patients in group II were
      subsequently treated with progestin-estrogen therapy and a normalization of
      pressure values was achieved in 10 of these (43.5%). These results suggest that
      hormonal treatment determines, in at least one third of the cases, a significant
      reduction in blood pressure values. Moreover, hormone replacement may be
      effective even in patients that have not responded to antihypertensive drugs.

PMID- 9177612
TI  - Familial hemiplegic migraine in developmental age: report of two cases.
AB  - The authors report two cases of a particular type of migraine with aura, known as
      familial hemiplegic migraine (FHM). According to the International Headache
      Society (IHS) diagnostic criteria, the FHM can be diagnosed with the exception of
      organic causes, in a patient with migraine with aura including emiparesis of
      anything severity and with an end occurring a member of the family with
      similarity in the attach pattern. The two clinical cases reported clearly show
      these features and they can be considered exemplary for this type of pathology.
      This rare type of migraine has an unknown etiology, it seems to depend on a
      decreases of cerebral blood flow originative on the occipital lobe, over the
      subsequentially spreading anteriory region temporal and parietal lobe. The
      hypoperfusion with the next following neural ischemia is related to the variation
      of blood flow and/or "the spreading depression" supported by Leao and Olesen
      recently. We wanted to show these two cases so that the psychiatrist, the
      pediatrician, and the neurologist can be able to refer parents to the right
      approach, considering possibility of a pathology rare but benign; this is the
      FHM.

PMID- 9177614
TI  - Ergonomic approach in aging: experimental procedures to assess cognitive and
      balance impairments.
AB  - This brief commentary is focused on the experimental procedures employed in the
      evaluation of both cognitive and balance impairments of aging patients. This is
      an important ergonomic issue that might be used for research purposes. In fact,
      the corrected assessment of impairments during aging may favor the development of
      new integrated ergonomic strategies to ameliorate ADL together with the reduction
      of environmental risks.

PMID- 9177615
TI  - Allergic rhinitis, olfactory disorders and secretory IgA.
AB  - The authors point out the possible relationship between the biochemical and
      immunological components of nasal mucus in subjects affected by allergic rhinitis
      and/or olfactory disorders. Fifty seven subjects (33 F, 24 M) aged between 19 and
      73 years, (median age 65 SD 14.60) were studied. Twenty seven of them were
      normosmic affected by allergic rhinitis and taken as control group, (14 were
      positive to allergometric tests and/or RAST, while the other 13 were negative),
      30 were dysosmic, and subdivided into parosmic (n = 6), anosmic (n = 15) and
      hyposmic (n = 9) (only one was negative both to allergometric tests and to RAST).
      In all patients we assessed: nasal mucus (it was analysed for: mucus quantity,
      pH, protein concentration, K+ concentration and the SIgA antibodies, tested both
      by radian immunodiffusion and by ELISA), allergometric tests, PRIST, RAST,
      anterior rhinomanometry, evoked olfactory potential. As regard to allergometric
      tests, we have no observed statistically significant differences between the
      control and the dysosmic group, although all the dysosmic patients (except one)
      were positive both to allergometric tests and to RAST. Total (PRIST) and specific
      (RAST) IgE values (except for the anosmic subjects who had IgE values moderately
      higher) were similar to the results obtained by allergometric tests. As regards
      to nasal secretion quantity, it was reduced (p: n.s.), like the pH (p: n.s.), in
      the parosmic subjects. On the other hand, proteins concentration of nasal
      secretion was lowered in hyposmic (p: n.s.) and anosmic (p = 0.05) subjects,
      while there were no differences between parosmic subjects and control group. The
      values of SIgA in controls and hyposmic subjects were not too different and
      similar to those observed by other authors; however they were slightly increased
      in controls affected by allergic rhinitis with positivity both to RAST and/or
      allergometric tests (p: n.s.), while they were reduced in the parosmic and
      significantly in the anosmic patients (p < 0.01). On the basis of that data, the
      authors conclude that, (though related to a limited case reports) being the
      secretory IgA values inversely proportional to the gravity of olfactory
      pathology, a their protective role (if the anatomic-functional substratum is
      efficient), in the pathologies examined, can be easily hypothesized. Besides,
      that data highlight that their concentration is slightly decreased in those
      patients affected by allergic rhinitis, without olfactory disorders (p: n.s.).

PMID- 9177616
TI  - Hemophilus influenzae type b meningitis: pediatric overview.
AB  - The authors valued the incidence and clinical therapeutic aspects of Haemophilus
      influenzae type b (Hib) meningitis in children. They report a retrospective
      study, in children, with diagnosis of acute purulent meningitis, from January
      1982 to December 1994, aged between 1 month and 14 years. Particular attention
      was direct to Haemophilus influenzae type b meningitis (20 cases). The incidence
      rate of Hib meningitis in the overall cases (89) was 22.47% (20), while among
      children younger than 5 years Hib was the most frequently pathogen isolated
      (20/58-34.47%). In 1/4 of cases, particularly in children younger than 1 years,
      exordium was aspecific and unclear. At admission culture and examination of
      Cerebrospinal Fluid (CFS) have been done. CFS was cultured on blood agar and
      chocolate plates. A latex agglutination test was used for rapid detection of the
      bacterial antigens. In some cases we looked for bacterial antigens in urine. 20%
      of children had complications and 10% had sequelae (1 years of follow-up). We
      didn't have any dead. Antibiotic treatment was principally with Ampicillin,
      Cephalosporin and Chloramphenicol. The results of this study confirm the Hib
      gravity and suggest that the administration of conjugate vaccine against Hib to
      all living in Italy is justified.

PMID- 9177617
TI  - Incidence of bacterial colonization in the throat and in urines at paediatric age
      with evaluation of sensitivity to common antibiotics.
AB  - OBJECTIVES: To evaluate the incidence of bacterial colonization in the throat and
      in urines of children admitted to a paediatric ward in the year 1994. To test the
      sensitivity of isolates on the most common antibiotics used in therapy. METHODS:
      The investigation was carried out on a group of 270 children (125 male and 145
      female), aged between 3 months and 12 years, hospitalized with feverish
      infectious pathology in the department of infectious and Tropical Diseases of the
      University "La Sapienza" of Rome. The cultures of the throat swabs and on urines
      were performed on the admission of the children before the beginning of the
      therapy. RESULTS: The throat-swab cultures showed pathogenous microrganisms in
      232 samples (85.9%) with a slight prevalence of Gram-negative bacteria (122) with
      respect to Gram-positive (110) and saprophytic microbial flora (38). The urine
      cultures proved to be positive in 81 cases (30%) with a prevalence of Gram
      negative (56) above Gram-positive isolates (25). CONCLUSIONS: The two/thirds of
      paediatric patients hospitalized in an Infectious Diseases Department appeared to
      be colonized in the upper respiratory tract, whereas in about 10% of them a
      marked bacteriuria was clearly evident, often in the absence of specific
      symptoms. A few isolates either from the throat or from urines, showed resistance
      to the common antibacterial agents.

PMID- 9177618
TI  - Serum uric acid and insulin secretion in diabetes mellitus.
AB  - In order to define the relationship, if any, between serum uric acid and insulin
      pattern in different types of diabetes mellitus, 4 groups of subjects (controls,
      and affected by type 1 and type 2 diabetes mellitus, with and without obesity)
      were considered. In each group, successively cleared of the long-term and
      complicated diabetic patients, serum and urinary uric acid and insulin secretion
      (serum C-peptide values) were determined. Serum uric acid and C-peptide values
      were higher in type 2 obese diabetic subjects vs the other groups of patients and
      controls (p < 0.001). No difference was found, on the contrary, between
      creatinine clearance and urinary excretion of uric acid among the groups.
      Moreover, serum uric acid values were in positive correlation (p < 0.02) with
      serum C-peptide values considering, among the diabetic subjects, only those with
      duration of diabetes less than 5 years and without micro-macrovascular
      complications. In conclusion, these data lead to presume that diabetic patients
      with short duration of disease and without complications show a different serum
      uric acid pattern, strictly related to beta-cellular secretion.

PMID- 9177619
TI  - The mouth-stomach crossing of Helicobacter pylori.
AB  - In order to confirm the mouth-stomach crossing of Helicobacter pylori (H. pylori)
      we performed a study to isolate the bacterium both from dental plaque and gastric
      mucosa of 83 subjects. Out of the 83 subjects, 62 were affected by gastroduodenal
      pathologies usually related to H. pylori whereas, the other 21 subjects were
      healthy. Each patient underwent one plaque sampling and three gastric samplings.
      The samples were cultured and an analytical technique, isoelectrofocusing (IEF),
      was used to show if dental and gastric strains isolated from the same subject had
      the same proteic profile. The H. pylori was isolated from the dental plaque of
      five subjects. Out of these, four subjects were suffering from gastric
      pathologies and the H. pylori was besides isolated from their gastric mucosa. The
      dental and gastric strains isolated from the same patient showed the same proteic
      profile. The hypothesis of H. pylori crossing from mouth to stomach seems to be
      confirmed.

PMID- 9177620
TI  - A possible case of carbamazepine induced pancreatitis.
AB  - The authors report a case of acute pancreatitis (AP) occurring in a patient under
      treatment with carbamazepine (CBZ) for post-traumatic petit mal epilepsy, and
      review the current literature of drug-induced AP. The evidence of high plasmatic
      levels of CBZ and the absence of other aetiologic factors lead the authors to
      conclude that the overdose of CBZ could have represented the precipitating of the
      episode of acute pancreatitis.

PMID- 9177621
TI  - Toxoplasmosis in pregnancy: research on 2295 women in Rome and its province.
AB  - The authors report the data concerning 2295 women tested for toxoplasmosis
      immunodiagnosis, in the Department of Infectious and Tropical Diseases of "La
      Sapienza" University of Rome in the years 1993-1994. Four hundred eleven cases
      (17.9%) were positive for IgG only; 2 cases (0.1%) for IgM only; 15 cases (0.6%)
      for both IgG and IgM while 1867 cases (81.4%) were negative. 1668 women were
      pregnant. In this group 260 (15.6%) were positive for IgG only, 2 (0.1%) for IgM
      only, and 10 (10.6%) for both IgG and IgM; in one case there was a spontaneous
      absorption in the 10th week of pregnancy, in another case a still-birth in the
      20th week with brain lesions; a child was born with phocomelia of the right arm
      and one with a clubfoot. While it is possible to explain the absorption and the
      still-birth with the toxoplasma infection, it is difficult to understand the
      causes of the abnormality of the limbs.

PMID- 9177622
TI  - HCV and dermatomyositis: report of 5 cases of dermatomyositis in patients with
      HCV infection.
AB  - The authors report five cases of dermatomyositis in which positivity for
      hepatitis C virus was ascertained. A virus-related (ECHO virus, Coxsackie)
      dermatomyositis is known, but a hepatitis virus C-related dermatomyositis was
      reported only in one case in a Letter to the Editor of Journal of Rheumatology
      (1994).

PMID- 9177623
TI  - Cardiovascular disease and Lp(a) in the adult population and in the elderly: the
      Brisighella study.
AB  - OBJECTIVE: The aim of this study was to evaluate the distribution of the
      concentrations of lipoprotein(a) [Lp(a)] in a free-living population, that of
      Brisighella, and to study the degree of association with cardiovascular disease
      (CVD) and other associated risk factors. The Brisighella study is included in the
      framework of observational and interventional longitudinal studies; it began in
      1972 to monitor the spontaneous trend of the risk factors for atherosclerosis and
      to evaluate the incidence of CVD in a rural population. METHODS: The studies were
      carried out on 1319 subjects, 627 males and 692 females, aged over 14 years, of
      which 134 men and 113 women were geriatric (age > 64 years); the data are
      relative to the control of the population in 1988. The following were evaluated
      for each subject: (a) weight and height; (b) hematological parameters; (c)
      clinical events; (d) presence of other concomitant diseases. For the dosage of
      the hematological parameters, enzymatic-colorimetric parameters were used (total
      and HDL cholesterol, triglycerides, glycemia and uremia), radial immunodiffusion
      and immunoturbidimetry (apoAI and B), ELISA-sandwich immunoenzymatic method
      (Lp(a)). All the methods used are standardized and internal and external
      laboratory quality control was carried out. The data collected were analyzed with
      the program STATGRAPHIC VERSION 6.0; the mean, the standard deviation and the
      median were calculated for all the variables. The frequency tables, distribution
      curves (approximation estimates with the chi 2 test), and single and multiple
      regression were also calculated. A value of p < 0.01 was taken as the level of
      significance. RESULTS: The distribution of Lp(a) in the control population and in
      subjects with CVD was substantially the same for both sexes; the differences
      between the mean levels of Lp(a) were not statistically significant (18.5 mg/dl
      vs 20.09 mg/dl for men and 19.98 mg/dl vs 22.78 mg/dl for women). The same also
      applies to the elderly population (18.81 mg/dl vs 23.31 in the men and 21.13
      mg/dl vs 21.47 mg/dl in the women). No significant variations were observed in
      the mean values of Lp(a) even when other risk factors were taken into
      consideration, such as hypertension, obesity and diabetes. Finally, multiple
      regression analysis did not show any correlation between Lp(a) levels and those
      of the other hematological parameters. CONCLUSIONS: In this transversal study, we
      found no evidence to suggest that Lp(a) can be considered and independent and
      predictive risk factor for CVD. It would therefore seem that in the population of
      Brisighella the levels of Lp(a) are "causally" distributed, without any
      correlation with the presence of cardiovascular events or with hypertension,
      diabetes or obesity in both sexes.

PMID- 9177624
TI  - Transcranial Doppler validation of hemodynamic vertebrobasilar insufficiency
      diagnosis.
AB  - Transcranial Doppler (TCD) can be useful in the diagnosis and validation of
      surgical treatment of vertebrobasilar insufficiency (VBI). A case is reported in
      which TCD confirmed the diagnosis of vertebrobasilar insufficiency and validated
      the indication of surgery by detecting a bidirectional flow in a stenotic and
      compressed vertebral artery. In the postoperative period and at late follow-up
      TCD demonstrated a restored antegrade flow, as a consequence of a well
      functioning revascularization. Surgical indication of VBI is rare and TCD can be
      proposed as part of routine patients' study before a surgical decision is taken.

PMID- 9177625
TI  - Effective treatment of osteoarthritis with a 150 mg prolonged-release of
      diclofenac sodium.
AB  - A new oral dosage form of diclofenac sodium, enabling the single administration
      of the daily dose of 150 mg, has been tested for treatment of 20 patients
      suffering from osteoarthritis of the spine. A control group of 20 patients with
      the same diagnosis instead received 3 enteric-coated tablets/day, each containing
      50 mg of the drug. Treatments lasted in both groups one month. Clinical efficacy
      was monitored by evaluating the changes in the disease's symptoms and signs
      (pain, cramps, alterations of function capacity, morning stiffness) and in some
      laboratory parameters (ESR, C-reactive protein, Rheuma test). Treatment
      tolerability was evaluated through the routine laboratory blood and urine tests,
      and by registering any complaint at the gastrointestinal level, as well as any
      adverse event. The two posology schemes were equally effective in favourably
      reducing the disease's clinical and laboratory manifestations. Also systemic and
      local tolerability were superimposable and on the whole good: only a few episodes
      of mild epigastralgia were reported (3 cases in each group), as expected during a
      treatment course with NSAIDs.

PMID- 9177626
TI  - Heparin induced thrombocytopenia after low molecular weight heparin treatment: a
      case report.
AB  - A case of low molecular weight heparin induced thrombocytopenia is reported.
      Mechanisms and treatment of this condition are discussed.

PMID- 9177627
TI  - Percutaneous management of benign renal cysts.
AB  - Percutaneous emptying of benign renal cysts represents the adopted treatment for
      this kind of pathology. The introduction of pure ethilic alcohol (95 degrees) is
      usually associated with emptying because it determines the necrosis of the
      secreting epithelious with recurrences and little significant complications. This
      treatment is the less bloody solution that can be executed in surgery and for
      this reason it is proposed in the time as an alternative to surgery treatment of
      removal.

PMID- 9177629
TI  - Perceptions of the MD-MPH option at Brown.

PMID- 9177628
TI  - Possible effects of reusing OSCE stations.

PMID- 9177630
TI  - New possibilities emerging in Russian medical education.

PMID- 9177631
TI  - Teaching conferences in family practice residencies.

PMID- 9177632
TI  - Faculty perspectives on residency site selection.

PMID- 9177633
TI  - Implications of the changing practice environment for family medicine education.

PMID- 9177634
TI  - Restructuring the role of psychiatry in medical education.

PMID- 9177635
TI  - Reengineering academic medical centers: reengineering academic values?
AB  - Academic medicine is entering an era of profound, unsettling change resulting not
      simply from the drastic transformation of the health care marketplace but more
      fundamentally from the chronic, growing gap between academic medicine's seemingly
      insatiable demand for total resources and the supply of resources that society is
      willing to provide. To examine this problem, the author reviews the major factors
      that have shaped the development of academic medical centers (AMCs) since World
      War II and are now the roots of their vulnerability. The first was the major
      federal investment in university-based programs of science research and education
      that began in the 1940s; the second was the enactment in the 1960s of the
      Medicare/Medicaid legislation that established federal responsibility for the
      support of graduate medical education. After describing important characteristics
      (e.g., number of faculty, number of students, dollars spent on research) of the
      growth and accomplishment that resulted from this massive infusion of federal
      funds over the last few decades, the author discusses several adverse
      consequences, such as the de-emphasis on education in favor of research and
      clinical service delivery and the serious disjunction between the internal labor
      markets of the AMCs and the external labor markets of the real world that AMCs'
      graduates enter. The author then analyzes the severe challenges being faced by
      academic medicine in research, education, and clinical practice in the emerging
      resource-limited environment. Of particular concern are the fate of the clinical
      investigator and the future of clinical research. The author concludes with a
      list of four feasible strategic options for AMCs (e.g., "build one's own system")
      and an extensive list of what he believes AMCs will do to respond to the stresses
      now upon them (e.g., capitalize on unique strengths rather than trying to compete
      in all areas). He concludes that it will take courage for AMCs to preserve their
      core values in the new era, but that this can be done if AMCs craft new adaptive
      structures that are better attuned to the new environment and not wedded to one
      that is vanishing.

PMID- 9177636
TI  - Preparing physicians for practice in managed care environments.
AB  - The author first describes the evolution and characteristics of managed care and
      its emphasis on the care of populations as well as individuals. She then reviews
      managed care's implications for medical education; for example, managed care
      physicians must know non-office-based approaches to keeping their patients
      healthy. She identifies and defines eight domains of knowledge in which
      physicians must be competent for practice in environments dominated by managed
      care. These are epidemiologic thinking, human behavior, organizational behavior,
      information systems, quality measurement and improvement, health system financing
      and delivery, ethics, and systems based care. Teaching students to practice in
      managed care environments is a challenge partly because there are few role models
      of the new breed of physician among medical school faculties. The author suggests
      strategies and attitudes to remedy this situation (for example, faculty must
      understand that managed care is not homogeneous and that it is not all bad;
      medical schools should develop "master teachers" for the rest of the faculty; and
      interactive CD-ROM-driven problem-based learning sets could be used). Focusing on
      training faculty for the new era and on emphasizing the eight knowledge better
      physicians, whether they practice inside or outside managed care.

PMID- 9177637
TI  - A state university's model program to increase the number of its disadvantaged
      students who matriculate into health professions schools.
AB  - Health professions schools often provide support for minority and disadvantaged
      students in high school or in a single college summer program. However, long-term
      support for students during their undergraduate years is also crucial. Since
      1990, San Diego State University (SDSU), a large urban public university, has
      implemented the Health Careers Opportunity Program (HCOP) to increase the number
      of the university's disadvantaged students (most of whom are from minority
      groups) who matriculate into medical, dental, veterinary, and physician assistant
      schools. The program's 11 components, each dedicated to some form of educational
      intervention and support, emphasize developing students' collaborative learning
      skills, fostering their pride in accomplishment, and helping them achieve
      positive self-images and self-confidence; these goals are linked with building
      students' analytical and problem-solving skills. Weekly journals kept by
      students' mentors serve as an "early warning system" for "bad" feelings,
      attitudes, and behaviors that reflect students' personal problems and correlate
      with lower grades, and help the program staff work intensively with students
      immediately, before problems become severe. The SDSU's HCOP increased the number
      of disadvantaged (mostly minority) students staying in the prehealth career path
      (not counting those in the schools of nursing and public health) from 70 in 1989
      to 360 in 1995. In 1992 through 1994, the students who had completed the HCOP's
      Summer Academic Program (to help them bridge into a science curriculum) had pass
      rates for entry-level math, writing competency, and math placement that were
      consistently higher than the rates for other SDSU students. The overall grade
      point average of HCOP students in the spring of 1995 (3.05) was significantly
      higher than the overall GPA of all minority students in prehealth training before
      the HCOP began (2.59 in 1988). The number of SDSU's minority students accepted by
      health professions schools (primarily medical schools) rose significantly from
      six in 1990 to 23 in 1995. It is clear that the labor-intensive interventions of
      the HCOP throughout students' years at SDSU until they matriculate into health
      professions schools are working.

PMID- 9177638
TI  - Extended educational sessions at three family medicine residency programs.
AB  - There are few descriptions of graduate medical education curricula in the
      literature, and the descriptions that have been written have focused more on
      content than on format. Traditionally, educational presentations in residency
      programs are offered in one-hour time slots, a format that may be too limited for
      interactive sessions or hands-on activities. Further, whether these one-hour
      sessions are offered in the morning, at noon, or in the afternoon, they all
      present hindrances to residents' attendance. The authors propose that reserving
      extended blocks of time for educational sessions for residents is one way for
      programs to ensure both that residents attend the sessions and that they are able
      to learn what they need to learn during their training to meet the special
      requirements of the appropriate residency review committee. The authors present
      the experiences of three family medicine residency programs in developing and
      implementing extended educational sessions. Each program has multiple training
      sites, including rural sites. The three programs release residents from their
      clinical responsibilities to enable them to participate in the half-day to day
      long sessions, which cover behavioral issues, procedures training, and other
      topics. The success of these three programs suggests that extended educational
      sessions are a viable alternative to the traditional one-hour format.

PMID- 9177640
TI  - Research in the Veterans Health Administration: new paradigm or changing
      priorities?

PMID- 9177639
TI  - What is the Internet learning about you while you are learning about the
      Internet?
AB  - Privacy, confidentiality, and security are largely taken for granted in
      physicians' offices. However, increasingly, physicians and insurance providers
      will be obtaining and exchanging information through the sophisticated resources
      available on the Internet and the World Wide Web (WWW, or the Web). Some of these
      resources will maintain the same privacy experienced in the office of a trusted
      clinician or in the reading room of a great library, but more often than not,
      while people are learning from the Web, the Web will be learning about them. The
      author describes a new type of file used by Web browsers (the "cookies" file)
      that may enable users to browse the Web more efficiently but that may also
      compromise the user's privacy. He then discusses exactly how abuses might occur
      if information obtained through cookies files is misused, particularly by health
      insurance providers. Finally, he considers privacy and confidentiality issues
      raised by computer-based medical records, and the role of the health care
      provider in maintaining confidential and helpful doctor-patient relationships in
      the face of rapid technological change and the pressures of managed care.

PMID- 9177641
TI  - The cost of VA-sponsored research.
AB  - BACKGROUND: Under pressures to reduce health care costs, clinical income is a
      shrinking source of support for research. Such pressures also threaten research
      at the medical centers of the Department of Veterans Affairs (VA). VA research is
      particularly vulnerable because medical care appropriations constitute a large,
      though unknown, source of support. This study measures the medical care component
      and the total of VA research funds. METHOD: The incremental costs of VA research
      were estimated from a survey of 497 clinician investigators and data on payroll,
      facility costs, and research grants and appropriations. RESULTS: The incremental
      costs of VA research totaled $541.4 million in the 1992-93 fiscal year. This
      included $245.6 million in federal appropriations for VA research, $33.1 million
      in research grants administered by the VA, and $262.8 million in support from
      other VA appropriations. Research added as much as $219.8 million to VA patient
      care costs. CONCLUSION: The VA is adopting strategies to increase the internal
      payoff of its research. The fiscal constraints facing VA and other academic
      medical centers mean that they will be able to support research with their own
      funds only when it benefits them directly.

PMID- 9177642
TI  - A survey of graduates in practice from the University of New Mexico's
      conventional and community-oriented, problem-based tracks.
AB  - PURPOSE: To survey graduates in practice from the first four classes of the
      University of New Mexico School of Medicine's (UNMSOM's) parallel curricular
      tracks, and compare data about the graduates' practice patterns, learning
      behaviors, and satisfaction with the profession of medicine. METHOD: Between 1979
      and 1993, the UNMSOM had two tracks for the first two years of medical school: a
      conventional track and the Primary Care Curriculum (PCC), a community-oriented,
      problem-based track. In 1990, a survey was conducted of the 140 graduates from
      the first four classes (1983-1986) who had completed their postgraduate training:
      40 from the PCC and 100 from the conventional track. Statistical methods included
      two-way analyses of variance, logistic regression, and chi-square, adjusted by
      Bonferroni methods. Comparisons between tracks are reported after adjustments
      were made for specialty effects. RESULTS: Thirty-three graduates (83%) from the
      PCC and 87 (87%) from the conventional tracks responded. The PCC graduates were
      much more likely to work in medically underserved areas, practice in publicly
      funded health care settings, and care for non-paying patients. The PCC graduates
      more often identified patient problems and curiosity as providing motivation for
      their learning. They more frequently studied clinical medicine and community
      health topics and spent time in community activities. The PCC graduates felt
      better prepared for practice by their undergraduate medical education. There was
      no difference between the graduates of the two tracks in the sizes of the
      populations in which they practiced, in the criteria they used for deciding on
      referrals to other physicians, in the ranges of community resource utilization,
      or in the degrees of satisfaction within their chosen professions. Large
      percentages of graduates from both tracks (67% conventional and 79% PCC)
      considered themselves to be practicing either primary care or a combination of
      primary care and non-primary care. In addition, 38% of all the graduates
      practiced in the state of New Mexico. More PCC graduates chose careers in family
      practice; however, no significant difference was found in a comparison between
      the proportions of PCC and conventional-track graduates who chose primary care
      careers. CONCLUSION: Track differences favorable to the PCC were evident in
      relation to the two major goals established by the program: to attract graduates
      to careers in primary care in rural and underserved areas and to provide
      graduates with self-directed, lifelong learning skills. Some expected track
      effects were not found.

PMID- 9177643
TI  - Student health policies of U.S. medical schools.
AB  - BACKGROUND: Medical students are at risk of exposure to bloodborne pathogens, yet
      few data are available about U.S. medical schools' policies to protect students.
      METHOD: A cross-sectional survey of the student affairs deans at the 126 U.S.
      medical schools was conducted in May 1994. A confidential questionnaire inquired
      about policies regarding vaccination for hepatitis B virus (HBV), blood and body
      fluid exposures, universal precautions training, and health and disability
      insurance for students. RESULTS: A total of 108 (86%) of the schools participated
      in the survey. Most (99, 92%) required either HBV vaccination, evidence of
      immunity, or a signed waiver refusing vaccination. Nearly all (94, 87%) required
      health insurance, and almost all (101, 94%) offered a plan (at a mean cost of
      $690 annually), but fewer schools (69, 64%) offered disability insurance. The
      schools frequently held students responsible for the costs of HBV vaccination
      (73, 68%), postexposure serologic testing (22, 20%), and treatment of training
      related medical problems (43, 40%). CONCLUSION: Most medical schools comply with
      current recommendations for preventing training-related exposures to bloodborne
      pathogens, illness, and injury, but students face a substantial financial
      responsibility for these services at a time when many have large debts. Many
      schools do not have disability insurance readily available for students. Medical
      schools should review their student health policies to protect students
      adequately.

PMID- 9177644
TI  - Influence of the interview on the evaluation of applicants to medical school.
AB  - PURPOSE: To determine whether medical school admission interviewers change their
      evaluations and impressions of applicants as a direct result of the interview.
      METHOD: In 1991-92, 419 applicants to the University of Virginia School of
      Medicine were interviewed by members of the admission committee in two separate
      half-hour sessions. After reviewing each applicant's folder, interviewers rated
      the applicant before the interview on six objective scales. After the interview,
      ratings were again made on the same six scales, on the same form, below the
      ratings made before the interview. Data were examined using paired t-tests,
      Pearson correlations, and stepwise multiple-regression analysis. RESULTS: Of the
      six scales, only the ratings of Commitment to Serve Others were not significantly
      changed by the interview; the ratings of Familiarity with Issues in Medicine
      changed the most (p < .01 by paired t-test). The ratings of Overall Impression
      increased for accepted applicants and decreased for rejected applicants.
      CONCLUSION: The interview did influence interviewers' ratings made before the
      interview, and in the direction consistent with admission decisions, which
      supports the continued use of the interview. Although the magnitude of the
      changes was not large, the changes validate the conviction that the interview
      aids in the selection of individuals for medical school.

PMID- 9177645
TI  - Comparing students' attitudes in problem-based and conventional curricula.
AB  - PURPOSE: To compare the attitudes of students in a new problem-based learning
      (PBL) medical curriculum and in the previous conventional curriculum after the
      second curriculum year, prior to the clinical clerkships. The authors
      hypothesized that the PBL students would have more favorable attitudes toward
      their learning environment, social issues in medicine, and their curriculum.
      METHOD: The students in the classes of 1995 (conventional curriculum) and 1996
      (PBL curriculum) at the Dalhousie University Faculty of Medicine were asked to
      complete two main questionnaires and a few additional items that measure
      attitudes. The admission variables of the two classes were equivalent. Their
      attitude ratings were compared using t-tests. RESULTS: Response rates averaged
      87% (73 of 84 students) and 68% (57 of 84) for the PBL and conventional classes,
      respectively. The students in the PBL class had more positive attitudes toward
      their learning environment on the subscales for enthusiasm and authoritarianism
      (i.e., they rated their curriculum more favorably for democratic decision
      making); they were less positive on the student-interaction subscale. No
      significant difference emerged between the two classes on any subscale for
      attitudes about social issues in medicine. The PBL students reported more
      positive attitudes toward their curriculum. CONCLUSION: The study results support
      the superiority of the PBL curriculum regarding the students' attitudes toward
      their medical education.

PMID- 9177646
TI  - Relationship between systematic feedback to faculty and ratings of clinical
      teaching.
AB  - PURPOSE: To examine whether frequent written feedback to faculty would improve
      their teaching in clinical settings. METHOD: Forty-four pediatrics faculty at the
      Medical College of Wisconsin participated in 1987 and 1988 in a prospective
      randomized trial of feedback about clinical teaching. During a six-month baseline
      period all the faculty were rated on ten teaching traits by residents and
      students using a seven-point Likert scale; evaluation summaries were placed in
      the teaching folders of the faculty. During a 12-month treatment period, 21
      faculty were randomly selected to be given directed feedback every two months in
      the form of mailed computer-generated summaries that contained the most recent
      and cumulative mean ratings for the individual faculty member and the department,
      as well as written comments. Mean ratings were compared within the feedback and
      control groups and between the two groups by using two-tailed paired t-tests and
      Student's t-tests, respectively. RESULTS: The faculty receiving feedback showed
      significantly increased ratings over time for the traits of knowledge (p = .025),
      demonstrates skill(s) (p = .001), provides feedback to trainee (p = .006), and
      sets reasonable expectations (p = .03). The faculty receiving feedback had an
      average increase in ratings across all ten traits that was significantly greater
      than the average increase of their control-group peers (p < .05). Those in the
      feedback group who had received mean ratings for overall teaching effectiveness
      that were below the department mean at baseline showed the greatest improvement
      by the end of the treatment period (p < .05). CONCLUSION: The provision of
      written feedback improved the ratings of teaching effectiveness, especially among
      the faculty who had been rated below average.

PMID- 9177647
TI  - Residents' ethical disagreements with attending physicians: an unrecognized
      problem.
AB  - PURPOSE: To evaluate the frequency and nature of ethical disagreements over
      patient care between housestaff and attending physicians. METHOD: During the
      spring of 1994, a cross-sectional survey about ethical disagreements was
      conducted of all 42 internal medicine housestaff at the West Virginia University
      Hospitals and all 51 faculty in the Department of Medicine at the West Virginia
      University School of Medicine. Chi-square analysis was used to compare
      categorical variables. RESULTS: Thirty-six (86%) of the residents and 41 (80%) of
      the faculty responded. The housestaff recounted 127 ethical disagreements between
      attending physicians and housestaff in the previous year; the attending
      physicians reported 19. A total of 32 residents reported at least one ethical
      disagreement with an attending physician during the previous year. When asked
      about their most troubling disagreement, 27 (84%) of these residents reported
      they had been distressed because they considered the treatment ordered by the
      attending physician to be futile. Only 11 residents (34%) had discussed their
      most troubling disagreement with the attending physician. Of the 24 residents who
      correctly identified that a formal process to resolve ethical disagreements with
      a physician did not exist, 17 desired one. CONCLUSION: The residents'
      disagreements with attending physicians over ethical aspects of patient care were
      common and usually concerned issues of overtreatment. Since most of the
      housestaff did not express their concerns, the attending physicians were largely
      unaware of them. The findings suggest that residency directors need to encourage
      housestaff to discuss their ethical conflicts with attending physicians.

PMID- 9177648
TI  - Housestaff experience, workload, and test ordering in a neonatal intensive care
      unit.
AB  - BACKGROUND: Little is known of how the inexperience or the clinical workload of
      housestaff affects the decisions they make in the neonatal intensive care unit
      (NICU). The authors hypothesized that less experienced interns would order more
      tests per infant than more experienced residents, especially under conditions of
      heavy workload. METHOD: The NICU at the University of Kentucky A. B. Chandler
      Medical Center has either an intern or a resident on call by himself or herself
      at night, a natural setting to compare test ordering by interns and residents.
      The authors counted the numbers of X rays, analyses of arterial blood gases
      (ABGs), and electrolyte determinations ordered by the house officers on call for
      321 infants from July through November 1993. Data for nine interns and seven
      residents were compared using multivariate linear regression. RESULTS: When
      workload became heavier (about five NICU patients), the interns increased their
      ordering of ABGs per infant to a significantly greater degree than did the
      residents (p = .01), with the difference being even greater on weekends when the
      housestaff were under less supervision (p = .004). CONCLUSION: As workload
      becomes greater in the NICU, interns order more ABGs per infant than do more
      experienced residents, especially when the interns are less supervised.

PMID- 9177649
TI  - Introduction--improving the transformation of data into knowledge.

PMID- 9177651
TI  - On rising medical student debt: in for a penny, in for a pound.
AB  - Using national databases of the Association of American Medical Colleges, the
      authors have examined reasons for the rising indebtedness of U.S. medical
      students, looking across the past decade at the influence of tuition and fees
      (tuition-fees) alone and the total costs of attending school, the effects of the
      changing demographics of medical school enrollments and lengthened graduation
      times, the relationship between the availability of school-funded scholarships
      and the amount of student loan disbursements, the pattern of student financial
      aid, and the reliance on borrowing to cover the costs of medical education. In
      constant dollars, the average indebtedness of students graduating from public
      schools increased 59.2% between 1985 and 1995, and that for graduates of private
      schools increased 64.2%. The fraction of graduates bringing debt with them when
      they entered medical school declined from 42.1% in 1985 to 33.6% in 1995.
      Premedical debt as a fraction of total debt declined at public schools from 9% in
      1985 to 7% in 1995, and at private schools from 7.8% in 1985 to 5.9% in 1995. For
      public schools, tuition-fees increased 60.1% between 1985 and 1995, and average
      medical school debt increased 60.9%; for private schools, tuition-fees increased
      30.1% over that period, while average medical school debt increased 66.2%. On
      average, public school graduates accrued debt greater than their four-year
      tuition-fee payments, while the average debt accrued by private school graduates
      was less than tuition-fee amounts. In 1995, graduates of public schools had debt
      accumulations representing 62% of the average total cost of attendance (tuition,
      fees, books, supplies, equipment, and living expenses), and the indebtedness of
      private school graduates was 55% of the average total cost, findings suggesting
      that total costs were the stronger driver of the amounts borrowed. On a national
      scale, the influences on medical school debt of longer graduation times, the
      growing number of women students, greater racial-ethnic diversity, and the
      admission of more older students age were negligible or small. The average
      parental income, adjusted to constant dollars, actually increased between 1985
      and 1995. For public schools, the aggregate amounts of student aid have climbed
      at a steeper rate than schools' tuition-fee revenues during the past decade. For
      public schools, tuition-fee revenues rose 66.7% between 1985 and 1995, while the
      amount of loans to students at public schools increased 92.7%. For private
      schools, tuition-fee revenues went up 36.5%, and the amount of loans to students
      rose 57.9% during the same period. Federal Stafford Loans represented the major
      financing source, increasing from 71.5% of public schools' tuition-fee revenue in
      1985 to 92.2% in 1995, and from 23% of private schools' tuition-fee revenue in
      1985 to 38% in 1995. Over the decade, scholarship support kept pace with tuition
      fee increases at public schools, but lagged behind the increases at private
      schools. The recent escalation of student debt has coincided with the lifting of
      the federal loan borrowing limits under the Higher Education Act. In parallel,
      entering medical students have declared their intentions to rely more heavily on
      loans as a means of financing. These findings, although based on national data
      and trends, provide a framework for exploration of the factors affecting
      educational costs and financing at individual medical schools. The importance of
      doing so is mounting, as students may be throwing caution to the winds in the
      more favorable climate for borrowing, ignoring indicators of changing practice
      opportunities and incomes ahead.

PMID- 9177650
TI  - The volume and mix of inpatient services provided by academic medical centers.
AB  - This is the first in a series of AAMC Papers that analyze the clinical spectrum
      of patients treated in the nation's teaching hospitals. As stated in the separate
      Introduction, "The Transformation of Data into Knowledge," subsequent papers will
      examine trends in the provision of care to the indigent and make comparisons of
      quality of care among teaching and non-teaching hospitals. These analyses,
      carried out by the AAMC's Center for the Assessment and Management of Change in
      Academic Medicine (CAMCAM), are made possible by a reorganization of the AAMC's
      information infrastructure, in which many formerly separate databases have been
      linked. The Introduction concludes with a description of specific AAMC-CAMCAM
      initiatives that are being planned. This initial analysis examines the volume and
      mix of clinical services provided by AMCs, examines trends in these services over
      time, and compares services provided at different AMCs, in different markets, and
      between AMCs and non-teaching hospitals. Data from a variety of sources were used
      in these secondary analyses. The American Hospital Association's Annual Survey of
      Hospitals database was used to analyze volumes of inpatient services provided in
      AMCs and other hospitals. The AAMC's Clinical-Administrative Data Service
      database was used to analyze the volume and mix of clinical services provided in
      individual AMCs. The Agency for Health Care Policy and Research's Nationwide
      Inpatient Sample was used to compare the mix of clinical services provided in
      AMCs and other hospitals. Volumes of inpatient services in AMCs changed little
      between 1991 and 1994 and totaled six million hospitalizations, 41 million
      inpatient days, and two million inpatient surgeries in 1994. The mix of inpatient
      services in AMCs also showed little variation over time among individual AMCs, in
      markets with both high and low managed care penetrations, between public and
      private AMCs, or between AMCs and non-teaching hospitals, with the ten most
      frequent diagnoses accounting for significant proportions of total services. In
      contrast, several specialized services were much more likely to be offered and
      provided by AMCs. Despite rapid change in the health care environment, the volume
      and mix of clinical services provided by AMCs have been relatively stable.
      Implications for hospital planners, service chiefs and administrators, medical
      educators, clinical investigators, and health policymakers are discussed.

PMID- 9177652
TI  - Epidemiological health study of a town exposed to chemicals.
AB  - The purpose of this survey was to assess the health status of community residents
      exposed to a 16-day release of Catacarb from a nearby refinery and to document
      the prevalence rates of symptoms and illnesses of this town. The health status of
      the exposed residents was compared to that of unexposed residents of a
      demographically similar control town. An epidemiologic study design was used and
      questionnaires were mailed to all households in both towns. Response rate was
      43%. Household cluster effects, gender, education, and race were controlled in
      the analysis. Questionnaire health data reveal increased reporting of symptoms in
      the exposed, specifically headaches, respiratory, visual, gastrointestinal, and
      dermatologic with odds ratios ranging between 1.3 and 3. Exposure relationships
      with increased symptoms and worsening of illnesses was found.

PMID- 9177653
TI  - Mortality in the elderly and ambient ozone concentration during the hot summer,
      1994, in Belgium.
AB  - Extensive investigations were carried out to study the relationship between daily
      mortality in the elderly, outdoor air temperature, and ozone concentration
      observed in Belgium during the hot summer, 1994. The two environmental variables
      were assessed through mean daily temperature and 24-hr ozone concentration, both
      measured the day before and averaged over the country. Data were stratified by
      terciles of mean daily temperature in order to reduce the degree of collinearity
      between the investigated environmental variables. In the first stratum, which
      ranged from 9.9 to 15.4 degrees C (41 days), mean daily temperature and 24-hr
      ozone concentration were not correlated while the mean number of daily deaths was
      higher when 24-hr ozone concentration increased from 45 to 55 micrograms/m3 (P <
      0.05). In the second stratum, which ranged from 15.6 to 20.3 degrees C (42 days),
      mean daily temperature and 24-hr ozone concentration were strongly correlated (r
      = 0.54, P < 0.0001). In this stratum, the number of daily deaths did not depend
      on the mean daily temperature but increased linearly with 24-hr ozone
      concentration within the range 25 to 85.5 micrograms/m3 (P < 0.001). After having
      examined the possible confounding effect of sulfur dioxide, nitrogen dioxide,
      fine particulates, and humidity, ozone was found to be the only investigated
      variable contributing to the increased daily mortality. In the third stratum,
      which ranged from 20.4 to 27.6 degrees C (40 days), mean daily temperature and 24
      hr ozone concentration were also strongly correlated (r = 0.71, P < 0.0001).
      Daily mortality, in this stratum, was correlated more with mean daily temperature
      (r = 0.68, P < 0.001) than with 24-hr ozone concentration (r = 0.55, P < 0.001).
      Nonparametric regression analyses were performed to model the number of daily
      deaths in the whole range of temperatures. These analyses confirmed the effect of
      24-hr ozone concentration on daily mortality already uncovered by the least
      squares regression analysis in the second stratum of mean daily temperature. In
      addition, at levels exceeding 20 degrees C, the effect of ozone concentration on
      daily mortality was enhanced by temperature owing to a positive interaction
      between these two variables. The present study thus demonstrated a statistical
      association between daily mortality, observed in the elderly during the hot
      summer, 1994, in Belgium, and ambient ozone concentration. This relationship was
      dependent on the range of temperatures.

PMID- 9177654
TI  - The internal burden of lead among children in a smelter town--a small area
      analysis.
AB  - Hettstedt, a city in former East Germany with a history of mining and smelting of
      nonferrous ores, has multiple lead waste deposits and the remains of a former
      lead and copper-silver smelter. A small-area analysis of lead concentrations in
      blood and in household dust was undertaken in a cross-sectional study to
      determine if children living near the sources had particularly high burdens of
      lead. The overall geometric mean of the region was 38.0 micrograms Pb/liter blood
      with a 95% confidence interval (CI) of 36.5-39.5. The burden of lead among
      children living in the region containing the lead tailings piles and adjacent
      smelters was almost twice as high (77.4 micrograms Pb/liter blood; 95% CI 65.0
      92.0). It decreased in the areas farther northeast from the smelter. Lead levels
      in the children residing in areas southwest of the smelters were not appreciably
      elevated. The same pattern was found in house dust lead concentrations. This
      analysis helped target areas where follow-up is needed and found that not only
      distance from lead sources, but also meteorological factors played an important
      role in lead exposure.

PMID- 9177655
TI  - Geriatric bone lead metabolism in a female nonhuman primate population.
AB  - A geriatric rhesus monkey (Macaca mulatta) population, previously exposed to
      lead, was investigated using 109Cd K X-ray fluorescence (K XRF) to determine
      whether metabolism of lead in bone was similar to that in human populations. The
      accumulation rate of lead into the tibia in this group of monkeys was determined
      to be 0.10-0.13 micrograms Pb (g bone mineral)-1 (microgram dl-1 year)-1, which
      compares well with human data, where the rate has been found to be 0.05-0.10
      microgram Pb (g bone mineral)-1 (microgram dl-1 year)-1. In addition, bone lead
      changes over a 10-month time period were investigated, but no statistically
      significant difference was found. A halflife for lead in "bone" was calculated by
      fitting a single exponential model to serial blood lead data; the mean half-life
      of lead in bone was found to be 3.0 +/- 1.0 years. Both endogenous and exogenous
      lead exposure were found to be low at the present time, 10 years after cessation
      of lead intake. It is concluded that rhesus monkeys are an extremely good animal
      model of human bone lead metabolism and, in addition, that further research is
      needed to provide a more complete understanding of lead metabolism in geriatric
      populations.

PMID- 9177656
TI  - Toxicokinetics of cadmium in lactating and nonlactating ewes after oral and
      intravenous administration.
AB  - We studied the toxicokinetics of cadmium on two groups of ewes, a lactating group
      and a nonlactating group, after single intravenous and oral administrations of
      cadmium chloride using a semisimultaneous method and a three-compartment model.
      The nonlactating ewes showed a low cadmium bioavailability (0.12-0.22%), a large
      steady-state volume of distribution (23.8 +/- 5.4 liter/kg), and a low blood
      clearance (0.20 +/- 0.03 liter/kg/day). Their mean residence time was 113 +/- 28
      days. The lactating ewes had a higher bioavailability (0.33-1.7%). Their mean
      residence time was close to that in nonlactating ewes despite a greater blood
      clearance (0.46 +/- 0.013 liter/kg/day) because the volume of distribution of
      cadmium in the body was larger (Vss = 48.8 +/- 10.3 liter/kg). Their cadmium
      clearance in milk, changing with time, remained low and could not explain their
      higher blood clearance. In one nonlactating ewe, a greater cadmium
      bioavailability (5%) increased cadmium in the body. Increased cadmium amounts
      could induce renal damage and shorten the mean residence time (78 days).

PMID- 9177657
TI  - Effect of kerosene and its soot on the chrysotile-mediated toxicity to the rat
      alveolar macrophages.
AB  - In order to examine the pulmonary toxicity of kerosene oil and its combustion
      product (soot) in asbestos-exposed rats, various biochemical and chemical
      parameters were assayed. Treatment of rats with a single intratracheal dose of
      chrysotile asbestos (5 mg) and kerosene (50 microliters) or its soot (5 mg) in
      combination led to an increased number of pulmonary alveolar macrophages (PAM),
      elevated levels of hydrogen peroxide, and thiobarbituric acid-reacting
      substances, alterations in the activities of primary (glutathione peroxidase and
      catalase) and secondary (glutathione reductase and glucose-6-phosphate
      dehydrogenase) endogenous antioxidant enzymes, and depletion in the levels of
      glutathione in PAM compared to the chrysotile, kerosene, or soot alone. These
      changes may indicate the generation of oxidative stress in the macrophages. The
      resulting oxidative stress may be subsequently critical in collapsing the
      cellular membrane, which may change the cell membrane permeability and may also
      damage the phagolysosomal membrane, thereby releasing the membrane bound enzymes
      as indicated by an increased leakage of intracellular acid phosphatase and
      lactate dehydrogenase. The injury to macrophages may trigger events that lead to
      lung fibrosis and/or malignancies in the exposed animals. This study may be
      helpful in understanding the etiology of certain clinical and pathological
      disorders in the population exposed simultaneously to both asbestos and kerosene
      or its combustion products.

PMID- 9177658
TI  - Metal and sulfate composition of residual oil fly ash determines airway
      hyperreactivity and lung injury in rats.
AB  - The biological effects of particulate matter (PM) deposition in the airways may
      depend on aqueousleachable chemical constituents of the particles. The effects of
      two residual oil fly ash (ROFA) PM samples of equivalent diameters but different
      metal and sulfate contents on pulmonary responses in Sprague-Dawley rats were
      investigated. ROFA sample 1 (R1) had approximately twice as much saline-leachable
      sulfate, nickel, and vanadium, and 40 times as much iron as ROFA sample 2 (R2),
      while R2 had a 31-fold higher zinc content. Four groups of rats were
      intratracheally instilled with a suspension of 2.5 mg R2 in 0.3 ml saline (R2),
      the supernatant of R2 (R2s), the supernatant of 2.5 mg R1 (R1s), or saline only.
      By 4 days after instillation, 4 of 24 rats treated with R2s or R2 had died,
      compared with non treated with R1s or saline, and pathological indices were
      greater in both R2 groups compared with the R1s group. In surviving rats,
      baseline pulmonary function parameters and airway hyperreactivity to
      acetylcholine challenge were significantly worse in R2 and R2s groups than in the
      R1s group. Numbers of bronchoalveolar lavage neutrophils, but not other
      inflammatory cells or biochemical parameters of lung injury, were greater in both
      R2 groups compared with the R1s group. These results reinforce the hypothesis
      that the composition of soluble metals and sulfate leached from ROFA, an emission
      source particle, is critical in the development of airway hyperreactivity and
      lung injury.

PMID- 9177659
TI  - Log-additive versus log-linear analysis of lead-contaminated house dust and
      children's blood-lead levels. Implications for residential dust-lead standards.
AB  - The Environmental Protection Agency has been mandated to develop a health-based
      standard for lead in residential dwellings in the United States. Prior estimates
      of the relationship between residential dust-lead levels and children's blood
      lead concentrations have usually been obtained by using a log-linear regression
      of blood-lead concentration on levels of lead-contaminated house dust. It remains
      unknown, however, whether the log-linear model or a frequently cited alternative,
      the log-additive model, is the preferable regression method for analyzing these
      data. Secondary analysis of the Lead-in-Dust Study data was undertaken to compare
      log-additive with log-linear regression analysis for the purpose of developing a
      health-based dust lead standard. Specifically, we were interested in comparing
      the log-additive and log-linear analyses in their ability to characterize
      adequately the relationship of dust-lead loading on various surfaces with blood
      lead concentrations among urban children and to develop a predictive model to
      estimate the risk that a child will develop an elevated blood-lead level on the
      basis of a known level of dust lead. We used two dust sampling methods, the
      Baltimore Repair and Maintenance (BRM) vacuum method and the wipe method, to
      compare the log-linear and log-additive models. The log-linear model was
      consistently superior to the log-additive model in its ability to explain the
      variability in the observed blood-lead concentrations of the studied children,
      for both the wipe sampler and the BRM sampler. In addition, the log-additive
      model often predicted only a limited increase in the probability of blood-lead
      concentrations exceeding 10 micrograms/dl as a result of doubling the dust-lead
      loading exposure, whereas the log-linear model consistently demonstrated a
      significant increase in the probability of blood-lead concentrations exceeding 10
      micrograms/dl. BRM lead loading explained additional variability in blood lead
      above and beyond that explained by wipe loading for both carpeted and uncarpeted
      floors. In contrast, wipe-lead loading explained significant additional
      variability after adjustment for BRM loading for both uncarpeted floors and
      interior window sills. Although BRM loading better predicted children's blood
      lead concentrations than did wipe loading, these differences were not
      statistically significant. We conclude that the log-linear model explained a
      greater percentage of the variability in blood-lead concentrations than did the
      log-additive model, indicating that the log-linear model should be the default
      model of choice for developing a dust-lead standard.

PMID- 9177660
TI  - Glaucoma therapy may take your breath away.
AB  - Chronic simple glaucoma is a common disease in old age and lowering intraocular
      pressure is the treatment strategy. Although this can be achieved surgically,
      medical treatment with eye drops is more often prescribed. Beta-antagonists are
      the class of drug most often chosen, although other medical therapies are
      available. Systemic absorption of beta-antagonist eye drops can cause unsuspected
      respiratory impairment. Physicians should be alert to the possibility of
      respiratory side-effects of topical therapy with beta-antagonists and whenever
      such side-effects occur should use alternative treatments.

PMID- 9177661
TI  - Community-acquired pneumonia in old age: a prospective study of 91 patients
      admitted from home.
AB  - OBJECTIVE: to characterize the background, aetiology, clinical course and outcome
      of community-acquired pneumonia (CAP) in elderly compared with younger patients.
      DESIGN: a 1 year prospective study. SETTING: a university hospital in southern
      Israel. PARTICIPANTS: ninety-one patients over 65 years who were hospitalized
      from their homes with CAP. These patients were compared with a reference group of
      54 CAP patients, aged 55-64 years. MEASUREMENTS: an intensive work-up (primarily
      serological) to identify the aetiological causes of CAP. The age groups were
      compared in terms of variables related to CAP. RESULTS: the proportion with
      pneumococcal infection, the most common aetiology for CAP, increased from 29.6%
      in the 55-64-year group through 45.6% in the 65-74-year group; up to 57.8% in the
      75+ group (P = 0.019). Chlamydia pneumoniae was identified as the aetiological
      agent in 26.4% of elderly patients. Mortality in patients > or = 75 years was 20%
      and was significantly higher than in the two younger age groups (P = 0.019). The
      leucocyte count was significantly higher among the elderly group (P = 0.013) and
      the serum urea concentration was higher in patients 75 years and older (P =
      0.025). The proportion of patients treated with antibiotics before admission
      decreased with increasing age (P = 0.026). CONCLUSIONS: CAP has more serious
      clinical and abnormal laboratory features in the elderly than younger patients,
      particularly in those over 75. In independent elderly people, the pneumococcus is
      the most common causative agent for CAP but other agents, particularly C.
      pneumoniae, are common. Initial antibiotic treatment for these patients should
      therefore include a macrolide.

PMID- 9177662
TI  - Complications of laparoscopic cholecystectomy in the ageing patient.
AB  - AIM: to determine the safety of simple laparoscopic cholecystectomy in ageing
      patients. METHOD: the outcome of patients between 60 and 70 years of age and
      patients over 70 who underwent laparoscopic cholecystectomy for symptomatic non
      malignant gallbladder disease was comparatively analysed. All patients over 60
      years of age with symptomatic gallbladder disease and without cholecholithiasis,
      septic shock, diffuse peritonitis, gallbladder malignancy, portal hypertension or
      contraindication for general anaesthesia were selected for simple laparoscopic
      cholecystectomy (n = 158). This group represents over 80% of all elderly patients
      undergoing biliary surgery at our department over this period. Group A (n = 97)
      included patients from 60 to 69 years of age. Group B (n = 61) comprised patients
      over 70 years. RESULTS: there was no difference in sex distribution between
      groups. Operative time and conversion rates were similar in both groups. The
      overall morbidity rate was 14.5%, with no statistically significant increase in
      group B (11% for group A vs 20% for group B). No perioperative mortality
      occurred. Recurrent biliary surgery was required in two patients from group B
      (3%). Postoperative endoscopic retrograde cholangiography and sphincterotomy was
      done in four patients from group A (4%). The mean postoperative stay was longer
      for older patients (group A, 3.1 (2.5) days; group B, 4.2 (4.3) days; P = 0.05).
      CONCLUSION: simple laparoscopic cholecystectomy is safe in the aged, even for
      patients over 70. This procedure is associated with a short hospital stay and low
      rates of re-admission and recurrent biliary surgery.

PMID- 9177663
TI  - Competence thresholds for the use of inhalers in people with dementia.
AB  - METHODS: the ability to learn three inhaler techniques of increasing levels of
      complexity was studied in 50 normal and demented inhaler-naive elderly people
      (mean age 81 years) with stable 10-point mini-mental test scores (MTS). There
      were 10 subjects in each of the following groups: MTS 8-10 (non-demented), MTS 7
      (borderline), MTS 6 (mild dementia), MTS 5 and MTS 4 (2 moderate dementia
      groups). The techniques were taught on one day and reassessed on the following
      day on consecutive days in ascending order of complexity. RESULTS: those with an
      MTS of 4 were unable to learn any of the techniques, while all the non-demented
      people could learn all three techniques. For the five-stage technique (standard
      metered dose inhaler) the 0% threshold (i.e. when none of the subjects was able
      to learn) was MTS 6, the 50% threshold (at least half but not all could learn)
      MTS 7 and the 100% threshold (all could learn) MTS 8. For the four-stage
      technique (inhaler with large spacer) the 0% threshold was MTS 5, the 50%
      threshold MTS 6 and the 100% threshold MTS 8. For the three-stage technique
      (inspiration-triggered inhaler) the 0% threshold was MTS 4, the 50% threshold MTS
      5 and the 100% threshold MTS 7. CONCLUSIONS: MTS can be used to determine the
      likelihood of a mild or moderately demented patient being able to learn a
      multiple-stage inhaler technique.

PMID- 9177664
TI  - The effect of long-term omeprazole on the glucose-hydrogen breath test in elderly
      patients.
AB  - OBJECTIVE: to test whether omeprazole taken for longer than 1 month causes an
      increase in the rate of small bowel bacterial overgrowth in elderly subjects.
      SUBJECTS: 44 elderly people, 22 taking omeprazole, 22 not taking omeprazole or H2
      receptor antagonists. MAIN OUTCOME MEASURES: rate of positive glucose-hydrogen
      breath tests; anthropometric measures and blood tests reflecting malabsorption.
      RESULTS: there was no difference in the rate of positive tests between those
      taking omeprazole (45%) and those not taking it (59%). The omeprazole group had
      significantly lower serum albumin concentrations. There was no difference in body
      mass index, mid-arm circumference, arm fold thickness, adjusted calcium
      concentration or haemoglobin levels. CONCLUSIONS: omeprazole does not cause
      increased bacterial shall bowel overgrowth in elderly subjects.

PMID- 9177665
TI  - Blood pressure and intellectual function in elderly subjects.
AB  - OBJECTIVE: to assess the relationship between hypertension and cognitive function
      in elderly subjects. METHODS: 17 subjects with uncomplicated hypertension (nine
      male, eight female) and 27 control subjects with similar educational level and
      age (18 male, nine female) were studied. These individuals were recruited,
      according to strict selection criteria, from a random sample of 120 elderly
      subjects living in the community, who had a normal Mini Mental State score. An
      extensive neuropsychological test battery, sensitive to mild cognitive
      impairment, was administered in standard conditions to measure attention,
      concentration and judgement, psychomotor speed, memory and learning. Affective
      disorders were also evaluated. In all patients a computed tomography scan was
      performed. RESULTS: subjects with high blood pressure had lower mean levels of
      performance in attentional measures; tapping test (inhibition of incorrect
      answers), three words-three shapes test (attempts; incidental memory) and
      reaction time to multiple stimuli. They also scored worse in clusters 1 and 2 of
      the Hamilton rating scale for depression. Confluent white matter lesions were
      found in nine hypertensive subjects (52.9%) and five controls (18.5%; P =
      0.0170). Lacunes were demonstrated in 11 hypertensive (64.7%) and four
      normotensive people (14.8%; P = 0.0007). In a multivariate analysis (logistic
      regression), three cognitive variables (tapping, Hamilton cluster 2 and Hamilton
      total score) remained significantly associated with hypertension, independently
      of the presence of cerebral lesions. CONCLUSIONS: in elderly otherwise normal
      hypertensive subjects, an attentional impairment may occur, which appears to be
      functional and possibly reversible rather than structural and progressive.

PMID- 9177666
TI  - Reported activities of daily living: agreement between elderly subjects with and
      without dementia and their caregivers.
AB  - OBJECTIVES: to determine how accurately information on disability provided by a
      caregiver (proxy respondent) reflected the opinion of subjects themselves, and if
      this agreement varied by severity of dementia or relationship of the caregiver to
      the subject. SETTING AND PARTICIPANTS: the study was based on data from the
      Canadian Study of Health and Aging, a multicentre study of dementia and health of
      Canadians age 65 and over. Eight hundred study subjects and their caregivers were
      independently interviewed regarding the subjects' activities of daily living
      (ADL). MEASUREMENTS: the percentage of subjects who were independent for
      individual ADL items and the agreement in these reports between subjects and
      caregivers were investigated using three-level kappa statistics. RESULTS: index
      subjects with caregivers other than spouses or offspring required more assistance
      with ADL. The reported percentage of independence decreased with increasing
      severity of dementia. There was more agreement between self- and proxy-reported
      level of independence for physical ADL than for instrumental ADL items. Agreement
      decreased with increasing severity of dementia. Few statistically significant
      differences were noted between level of agreement and caregiver relationship.
      CONCLUSION: satisfactory levels of agreement on ADL between cognitively normal
      subjects and their caregivers indicate that proxy respondents are a reasonable
      source of information on ADL when data collection from the subjects themselves is
      not feasible. Since agreement decreases as the severity of dementia increases,
      caregiver reports may be preferred for elderly patients even with mild dementia
      in order to facilitate longitudinal assessment of ADL ratings as the dementia
      progresses.

PMID- 9177667
TI  - Activities of daily living: changes in functional ability in three samples of
      elderly and very elderly people.
AB  - OBJECTIVES: to investigate changes in functional ability and physical health,
      psychiatric morbidity, life satisfaction, service use and social support. DESIGN:
      a structured interview survey of three samples of elderly people living at home
      at two points in time. The three samples comprised one census of people aged 85
      and over [City (of London) and Hackney], and two random samples of people aged 65
      84 (City and Hackney and Braintree). The follow-up interviews took place 2.5-3
      years after the baseline interviews. SETTING: City and Hackney (East London) and
      Braintree (Essex). Respondents were interviewed at home by one of 12 trained
      interviewers. SUBJECTS: 630 people aged 85+ at baseline (70% response rate) and
      78% of survivors re-interviewed at follow-up; 464 people aged 65-84 in Hackney at
      baseline (67% response rate), and 83% of survivors re-interviewed; 276 people
      aged 65-84 in Braintree at baseline (82% response rate), and 78% of survivors re
      interviewed. MAIN OUTCOME MEASURES: scores on scales of functional ability,
      psychiatric morbidity, life satisfaction and social support, and items measuring
      number and type of health symptoms and services used. CONCLUSIONS: decreasing
      levels of physical functioning were associated with poor mental health, trouble
      with feet and problems with muscles and joints. There were no associations with
      level of physical functioning and use of rehabilitative or general medical
      services, use of social worker or carer relief. Few respondents used preventive
      or rehabilitation services.

PMID- 9177668
TI  - Morbidity and disability in elderly Zimbabweans.
AB  - BACKGROUND: the population aged over 60 years in Zimbabwe is expanding. Despite
      the likely increased demand on medical services that this will bring, little is
      known about the health needs of this elderly population. OBJECTIVE: to record the
      prevalence of disability (impairment of activities of daily living), subjective
      morbidity (symptoms), the social circumstances and the utilization of health
      services in a group of elderly Zimbabweans. DESIGN: cross-sectional community
      survey. SETTING: a remote rural area in North Eastern Zimbabwe and two urban
      townships located approximately 80 km from Harare. SUBJECTS: 278 subjects (154
      women, 174 rural), aged > 60 years (range 60-92) living at home. METHOD: subjects
      were selected by random cluster sampling. They were assessed in a structured
      interview and underwent physical examination including visual acuity, inspection
      for cataracts and assessment of mobility. RESULTS: less than 4% experienced
      difficulty with self-maintenance activities of daily living, but 30% had
      difficulty with instrumental activities. The former were all visually impaired
      and both visual and mobility problems contributed to the latter. Elderly people
      experienced many symptoms but had inadequate access to health services and used
      medication infrequently. Subjects were mainly self-sufficient for financial
      income and 60% still worked. They had declining resources with age and received
      little help from the social welfare department. Their health and functional
      abilities deteriorated with age but it was older subjects who had most difficulty
      getting to the clinic. Simple measures such as cataract surgery and analgesics
      were available only to the minority or not at all. CONCLUSIONS: this study
      highlights problem areas where simple, low-cost measures could make a difference
      to the morbidity and disability of elderly Zimbabweans.

PMID- 9177669
TI  - Casemix for inpatient care of elderly people: rehabilitation and post-acute care.
      Casemix for the Elderly Inpatient Working Group.
AB  - BACKGROUND: defining contracts for the care of elderly people on the basis of the
      number of episodes is inappropriate as it fails to take account of the wide
      variation in their physical disability and rehabilitation needs. Resource use on
      a day-to-day basis can be estimated for patients using the Resource Utilization
      Groups version III (RUG-III) casemix system. For practical use, RUG-III
      assessments cannot be made daily and so assessments at different time intervals
      were evaluated in order to give an indication of resource use for an inpatient
      stay. This study describes how RUG-III assessments can be used to give an
      indication of resource use for an inpatient episode. METHOD AND RESULTS: RUG-III
      assessments were completed for all admissions to elderly care rehabilitation
      wards in two Health Districts over a 10 week period. There were 336 patients and
      965 RUG-III assessments. The average time required to make RUG-III assessments
      fell from 10 to 4 min by the end of the study period. Fortnightly assessment
      intervals including a discharge assessment correlated well with the average of
      weekly assessments (R2 = 0.88-0.91, P < 0.0001). CONCLUSION: using the results
      from these assessments we propose a model for use of the RUG-III system in
      contracts for rehabilitation and post-acute care of elderly people which
      addresses the difficulty of combining clinical characteristics, rehabilitation,
      resource use and length of stay into a single useful meaningful casemix system.

PMID- 9177670
TI  - What degree of medical treatment do nursing home residents want in case of life
      threatening disease?
AB  - AIM: to examine the degree of medical treatment wanted by nursing home residents,
      their relatives and staff members should the resident develop a serious and life
      threatening disease and to analyse the degree of agreement between the wishes of
      these parties. DESIGN: an epidemiological, descriptive cross-sectional study.
      MATERIAL AND METHODS: the study population consisted of 101 competent and 106
      incompetent residents from 16 nursing homes; 142 relatives and 207 staff members
      were also interviewed. A hypothetical disease story was presented to residents,
      relatives and staff members and their choices classified into four groups
      according to degree of treatment. RESULTS: direct comparisons for the individual
      resident showed the greatest degree of disagreement whether to accept or refuse
      referral to hospital between relatives incompetent residents and staff members,
      in that the preference for curative treatment was significantly more frequent
      among the relatives. CONCLUSIONS: nursing home staff should try to discuss with
      relatives of incompetent residents their preferences for treatment in case the
      resident develops a serious disease before an acute situation arises.

PMID- 9177671
TI  - Determinants of age-associated changes in os calcis ultrasonic indices in elderly
      women: potential involvement of geriatric hyposomatotropism in bone fragility.
AB  - OBJECTIVE: ultrasound measures a clinically relevant property of bone strength in
      addition to and distinct from bone mass. The aim of the present study was to
      examine the effects of healthy ageing on ultrasound measurements of the
      calcaneus. DESIGN: cross-sectional study. STUDY PARTICIPANTS: a sample of 177
      community-dwelling healthy women aged 70-87 years. Exclusion criteria were
      diseases or medications known to affect the musculoskeletal system or the
      somatotrophic axis. MEASUREMENTS: serum levels of 1,25-dihydroxyvitamin D3 and
      insulin-like growth factor-I (IGF-I) were measured by radioimmunoassay, serum 25
      hydroxyvitamin D3 (25(OH)D3) was determined by competitive binding assay and
      serum parathyroid hormone was assessed immunochemically. Isometric and isokinetic
      quadriceps strength were evaluated using a Cybex II system. Calcaneal ultrasound
      indices--broadband ultrasound attenuation (BUA) and speed of sound (SOS)--were
      measured with an Achilles system. RESULTS: we found a significant decrease with
      ageing in BUA and SOS (-0.5 and -1.3% per year, respectively), suggesting a
      continuing loss of bone quality. Quadriceps strength, serum IGF-I and 25(OH)D3
      constituted the best predictors of BUA, while IGF-I was the only parameter found
      to be independently associated with SOS. CONCLUSION: these findings suggest that,
      among other factors, the activity of the growth hormone-IGF-I axis is of
      importance for skeletal integrity. Age-related bone fragility may, in part, be
      related to geriatric hyposomatotropism.

PMID- 9177672
TI  - CYP2D6, NAT2 and CYP2E1 genetic polymorphisms in nonagenarians.
AB  - BACKGROUND: enzymatic polymorphisms affecting the metabolic disposition of
      xenobiotics may modulate the rate of activation or deactivation of carcinogens
      and other toxic environmental chemicals. Hence, these polymorphisms may influence
      the risk of suffering some types of cancer and other degenerative diseases that
      are incompatible with extreme longevity. AIMS: to establish the distribution of
      three well known enzymatic polymorphisms that affect the CYP2D6, NAT-2 and CYP2E1
      genes and the activity of their enzymatic gene products, involved in the
      disposition of many xenobiotics, in a group of nonagenarians and in much younger
      controls. PATIENTS: the three genotypes were determined in 41 nonagenarians (10
      males, mean age 92.2 years, range 90-98) free of known malignancies or
      neurodegenerative diseases. The control groups comprised 217 healthy volunteers
      (128 males, mean age 36.3 years; SD, 12.7) for the CYP2D6 and NAT2 genotypes and
      137 (116 males, mean age 32 years; SD, 18.8) for the CYP2E1 genotype. METHODS:
      after extraction of DNA from white blood cells, polymerase chain reaction and
      restriction fragment polymorphism methods were used to identify the allelic
      variants of the three genotypes. RESULTS: we found no qualitative or quantitative
      difference in the mutations underlying the three genetic polymorphisms studied,
      nor in the expected enzymatic phenotypes. Instead, a close parallelism exists
      between advanced age and younger groups. CONCLUSION: longevity does not seem to
      be related to any special configuration of these three polymorphic traits.
      Comparisons with younger controls may be adequate when studying the distribution
      of these polymorphisms in diseases affecting old people. No genetically
      determined differences in the activation of drugs metabolized by these enzymes
      are to be expected in very old people.

PMID- 9177673
TI  - Acute phase proteins, C-reactive protein and serum amyloid A protein, as
      prognostic markers in the elderly inpatient.
AB  - AIM: to study the clinical significance and potential utility of measuring serum
      amyloid A protein (SAA) compared with the classical acute phase protein, C
      reactive protein (CRP). METHOD: a 3 month prospective study on 66 women, mean age
      83 years (range 69-106) and 33 men, mean age 84 years (range 69-95), admitted to
      the geriatric medicine unit at Hammersmith Hospital. CRP and SAA were determined
      on admission and at intervals throughout hospital stay; outcome end-points were
      death during the study, detection of infection, duration of admission and early
      re-admission to hospital after discharge. RESULTS: CRP and SAA responses were
      highly correlated (r = 0.75, P = 0.0001). However, the SAA response was greater
      than that of CRP in most individuals, with a median ratio of initial SAA to CRP
      of 2.2 in patients with infective pathology and 1.6 in those with inflammatory
      pathology. Median (range) SAA on admission was 98 (0.1-940) mg/ml in patients
      with infection and was twice that observed in patients with other causes of
      inflammation, median value 50 (0.6-699) mg/l. There was no difference between
      median CRP on admission in patients with infection or inflammation, median value
      53 (0.1-235) and 51.5 (5-246) mg/l respectively. Initial and peak levels of CRP,
      but not of SAA, were significantly greater in patients who subsequently died,
      whereas high levels of both proteins predicted length of admission and early re
      admission. CONCLUSION: major elevations of the serum concentrations of CRP and
      SAA indicated serious disease and predicted poor outcome. Measurement of SAA as
      well as CRP enhanced the clinical utility of monitoring the acute phase response
      in 7% of patients with a diagnosis of infection.

PMID- 9177674
TI  - Loss of vision in the ageing eye. Research into Ageing Workshop, London, 10 May
      1995.

PMID- 9177675
TI  - Does it make sense to speak of senile dementia?

PMID- 9177676
TI  - High-efficiency blotting of proteins of diverse sizes following sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis.
AB  - High-molecular-weight proteins often blot onto nitrocellulose membranes poorly
      following sodium dodecyl sulfate-polyacrylamide gel electrophoresis, resulting in
      low levels of detection on immunoblots, and hence difficulty in analyzing rare
      proteins. Moreover, optimizing conditions for the transfer of high-molecular
      weight proteins to nitrocellulose frequently results in the inefficient transfer
      or loss of lower molecular weight proteins. This problem is particularly vexing
      during the analysis of large proteins which may be processed to one or more
      smaller biologically active forms. Using radiolabeled protein standards and
      phosphorimaging technology, we have quantitated the efficacy of many different
      protein gel electrophoresis and blotting protocols. Here we report novel gel and
      blotting conditions which significantly improve the transfer and retention of
      high-molecular-weight proteins, without sacrificing the efficient transfer of
      lower molecular weight proteins. Using this newly described procedure, we have
      detected a rare 500-kDa protein in immunoblots which was previously not
      detectable with any of the commonly used blotting procedures. Since the improved
      conditions offer increased sensitivity across a spectrum of protein sizes, they
      should be widely applicable.

PMID- 9177677
TI  - In situ nitric oxide (NO) measurement by modified electrodes: NO labilized by
      photolysis of metal nitrosyl complexes.
AB  - Described are studies directed at refining quantitative analysis of nitric oxide
      in solution using electrochemical techniques. The fabrication and behavior of
      several sensors based on modified carbon-based electrodes are reported. This
      technique has been used to resolve the vexing problem of determining the
      stoichiometry of the photochemical decomposition of the known antihypertension
      agent sodium nitroprusside, Na2[Fe(CN)5NO], as well as of two other metal
      nitrosyl complexes of biological interest, Roussin's black salt, NH4[Fe4S3(NO)7],
      and Roussin's red salt, Na2[Fe2S2(NO)4], in aqueous solutions. In this manner it
      was shown that the molar ratios of nitric oxide produced per starting complex
      photochemically decomposed were 0.95 +/- 0.03, 5.9 +/- 0.2, and 0.50 +/- 0.02 for
      Na2[Fe(C-N)5NO], NH4[Fe4S3(NO)7], and Na2[Fe2S2(NO)4], respectively.

PMID- 9177678
TI  - The development of beta-lactamase as a highly versatile genetic reporter for
      eukaryotic cells.
AB  - We describe in this report that TEM-1 beta-lactamase has several desirable
      characteristics as a genetic reporter. First, it has no endogenous counterpart in
      eukaryotic cells and therefore provides a background-free measure of gene
      expression. Second, because of the uniqueness of the substrate cleavage reaction,
      a wide variety of substrates which are efficiently cleaved can be synthesized for
      beta-lactamase. Third, since the assays involve no more than addition of
      substrate to media, it is possible to continuously monitor a culture without
      destruction of the cells. Fourth, the enzyme is extremely versatile in that it
      can be fused to other proteins and retain activity. To demonstrate the
      versatility of beta-lactamase, we created three forms of the enzyme including
      secreted, intracellular, and membrane-bound forms of the enzyme, each form having
      distinct advantages as a reporter system. We also showed that levels of secreted
      beta-lactamase were proportional to both the levels of transfected DNA, beta
      lactamase mRNA, as well as activity of the chloramphenicol acetyl transferase
      gene controlled by the same promoter, validating the reliability of this
      reporter. beta-Lactamase thus represents a novel and highly versatile genetic
      reporter.

PMID- 9177679
TI  - Quantitative dynamic multicompartmental analysis of cholecystokinin receptor
      movement in a living cell using dual fluorophores and reconstruction of confocal
      images.
AB  - Receptor regulation is a key component of the phenomenon of desensitization in
      response to agonist stimulation which protects cells from overstimulation.
      Receptor internalization is one part of this response, often quantified by the
      portion of saturable ligand binding which becomes resistant to acidic washes. It
      is now clear that this can include receptor in multiple distinct cellular
      compartments. We have developed a morphological technique involving dual
      fluorescent probes to delineate the plasmalemma and the ligand-occupied receptor
      using confocal microscopy, with analysis involving three-dimensional
      reconstruction and quantitation of receptor movement through each compartment.
      When a radioiodinated cholecystokinin (CCK) analogue occupied its receptor on the
      CHO-CCKR cell line, it became progressively more resistant to dissociation with
      acidic medium. Quantitation of receptor internalization in these cells over time
      using this dynamic morphological technique correlated with the acid-resistant
      receptor fraction, and provided the additional information of the cellular
      compartments traversed. This technique will have multiple applications to explore
      the cell-specific handling of this and other ligand-occupied receptors.

PMID- 9177681
TI  - Bacterial typing: storing and processing of stabilized reference bacteria for
      polymerase chain reaction without preparing DNA--an example of an automatable
      procedure.
AB  - This paper examines the use of bacteria killed on blood-storage paper as
      templates (ghosts) and takes, as an example, the PCR ribotyping (amplification of
      the intergenic spacer regions between the 16S and 23S ribosomal RNA genes) of
      bacteria as described by Kostman et al. (J. Infect. Dis. 171, 204-208, 1995). All
      procedures have been particularly designed to be compatible with automation. DNA
      preparation is inappropriate for routine, high-volume sequence amplification from
      a diversity of microorganism cultures. Blood-storage/processing media provide
      another way of processing samples for PCR with distinctive aspects of increased
      safety and ease of automatibility. Blood-storage paper can be used for killing
      and processing bacteria to DNA-containing ghosts for reliable PCR. From as little
      as a few microliters of an overnight culture or a reasonably sized, single
      colony, rapid processing of large sample numbers is possible. FTA blood-storage
      medium has additional utility in that long-term cataloguing, storage, and
      processing of paper, loaded with culture, for PCR, is possible via a variety of
      sample wash sequences. It can be performed at convenience, after collection, and
      can be delayed indefinitely. using this approach, the repeatability of some PCR
      ribotyping methodology of the type used by Kostman et al. (J. Clin. Microbiol.
      30, 2084-2087, 1992) was examined as an exercise to demonstrate the practicality
      of FTA blood-paper usage and to check some basic features of PCR ribotyping. Five
      strains of Staphylococcus and one strain Escherichia coli were stored and
      processed on FTA blood paper, the PCR-ribotype patterns were analyzed and found
      to be the equal of patterns previously seen via additional DNA preparations.

PMID- 9177680
TI  - Long-lifetime metal-ligand pH probe.
AB  - We describe the synthesis and fluorescence spectral characterization of a pH
      sensitive metal-ligand complex, [Ru(deabpy)(bpy)2]2., where deabpy is 4,4'
      diethylaminomethyl-2,2'-bipyridine. This metal-ligand complex (MLC) was found to
      display pH-dependent intensities, emission spectra, and decay times, with the
      changes centered near the physiological useful pH value of 7.5. The apparent pKa
      values were not found to be dependent on ionic strength. The compound was found
      to be useful for lifetime-based sensing by phase-modulation fluorometry. Global
      analysis of the intensity decays over a range of pH values revealed two decay
      times of 235 and 380 ns, associated with the protonated and unprotonated forms,
      respectively. Because of its long decay time, optical pH measurements could be
      accomplished by phase-modulation fluorometry with a conveniently low modulation
      frequency of 700 kHz. The lifetime data were obtained with either a amplitude
      modulated laser or with an amplitude-modulated blue-light-emitting diode. This pH
      sensitive complex also displays a modest spectral shift with change in pH,
      allowing its use as a wavelength-ratiometric MLC probe. One can imagine lifetime
      sensors for a variety of blood cations and point-of-care assays based on long
      lifetime metal-ligand complexes and simple solid-state light sources and
      detectors.

PMID- 9177682
TI  - Sequential purification of human apolipoprotein B-100, albumin, and fibrinogen by
      immunoaffinity chromatography for measurement of protein synthesis.
AB  - A determinant of the accuracy of protein synthesis measurement using stable
      isotope is the purity of the protein under study. An Immunoaffinity
      chromatographic technique to sequentially purify human plasma albumin,
      fibrinogen, and apolipoprotein B-100 (ApoB-100) was developed to measure isotopic
      enrichment in these proteins. The technique, utilizing immobilized mouse
      monoclonal antibodies specific to human plasma ApoB-100, albumin, and fibrinogen
      onto an affinity matrix, allowed purification of very low density lipoprotein
      (VLDL) ApoB-100, albumin, and fibrinogen from 1- to 2-ml plasma samples.
      Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by
      silver staining demonstrated consistent purity of the three purified proteins.
      The identity and the purity of the proteins separated by this technique were also
      confirmed by amino acid sequence analysis. This technique was applied to
      sequentially purify and measure the isotopic enrichment in those proteins by mass
      spectrometry from human plasma samples collected after orally ingesting L[1-13C]
      leucine. Reproducibility of the enrichment measurements is within 5% of the
      coefficient of variation. Measurements [13C]leucine in these proteins purified
      from plasma samples collected during a 10-h primed continuous intravenous
      infusion of L-[1-13C]leucine confirmed that this technique provides an efficient
      way to purify plasma VLDL ApoB-100, albumin, and fibrinogen for measuring their
      synthetic rates in human metabolism studies.

PMID- 9177684
TI  - An enzyme-linked immunosorbent assay for detecting proteolytic activity of
      hepatitis C virus proteinase.
AB  - An ELISA method for the quantitation in vitro of HCV serine proteinase activity
      was developed. A peptide substrate, Ac-Gly-Glu-Ala-Gly-Asp-Asp-Ile-Val-Pro-Cys
      Ser-Met-Ser-Tyr-Thr-Trp-Thr-L ys (biotin) -OH (Sub-1), was hydrolyzed by a
      recombinant NS3 proteinase fused with maltose binding protein (MBP-NS3) into a
      product with a free amino moiety at the N-terminus. The product was immobilized,
      and the amino moiety was analyzed by digoxigenin labeling followed by
      immunological reaction with anti-digoxigenin-alkaline phosphatase conjugate and
      then the colorimeteric reaction. This method is suited for the high throughput
      screening of inhibitors, and the screening can be accelerated by automatic
      operation.

PMID- 9177683
TI  - Evaluation of antioxidant activity by chemiluminescence.
AB  - A sensitive and simple chemiluminescent method for measuring antioxidant activity
      was developed. The method is based on antioxidant-dependent quenching of
      chemiluminescence generated from lipid hydroperoxide and
      isoluminol/microperoxidase reagent. This method was used to evaluate the
      antioxidant ability of various antioxidants by measuring the half-inhibition
      concentration (IC50). The results were compared to those measured with an oxygen
      electrode method. They were approximately similar in pattern and level, although
      there was some discrepancy, which was assumed to be due to a possible difference
      in the reaction mechanisms of the two methods. This method also suggested an
      additive property of antioxidant activity with different antioxidants. Thus, the
      present method was used to evaluate the total antioxidant activity in biological
      tissues such as rat serum, human saliva, and green tea.

PMID- 9177685
TI  - Multistep denaturation and hierarchy of disulfide bond cleavage of a monoclonal
      antibody.
AB  - A humanized, monoclonal antibody of the IgG4 class was treated with SDS at room
      temperature. Analysis using SDS-PAGE revealed the progressive formation of a
      series of denaturation intermediates, of increasing apparent molecular weights.
      The detectable species migrated with apparent molecular weights of 137, 152, 162,
      182, 196, and 210 kDa. Antibody not incubated in SDS had an apparent molecular
      weight of 137 kDa, while boiling in SDS provoked the immediate conversion of all
      antibody to the slowest migrating form (210 kDa). A study designed to test if all
      rungs of the ladder were equally cleavable by mild treatment with mercaptoethanol
      revealed small amounts of a novel form, and conditions were devised to generate
      large amounts of this novel form. The novel form, before full denaturation,
      migrated at the position of unheated, intact antibody (137 kDa), while full
      denaturation in SDS converted the novel form to a species migrating at about 190
      kDa. The novel form, before full denaturation, was identified as HHL ***L, where
      the asterisks indicate noncovalent binding of one light chain to HHL. This
      noncovalent complex remains intact during SDS-PAGE. The novel form, after full
      denaturation, was identified as HHL. This study, with earlier studies, reveals
      that different pathways of reductive cleavage are taken by different antibodies,
      and that the most sensitive disulfide bond is different for different antibodies.
      Our results on antibody denaturation serve as a warning to those who use two
      dimensional gels for the analysis of antibodies.

PMID- 9177686
TI  - Mass spectrometry of whole proteins eluted from sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gels.
AB  - In this report we describe a novel approach to the mass spectrometric analysis of
      whole proteins from gels. The strategy consists of three components: conventional
      SDS-PAGE gels, reversible negative staining procedures, and passive elution of
      proteins from gels followed by mass spectrometric analysis. Protein bands are
      excised from SDS-PAGE gels, destained, and extracted. For gel loadings > or = 25
      pmol of soluble protein, the proteins can be directly extracted into a solution
      consisting of formic acid/water/2-propanol. The recovered protein is suitable for
      matrix-assisted laser desorption/ionization (MALDI) or electrospray ionization
      mass spectrometric analysis. For gel loadings < 25 pmol protein, the mass
      spectrometric response, using the direct extraction procedure, drops off sharply,
      an outcome that is attributed to protein recovery losses. To offset the protein
      losses, the extraction procedure is slightly modified by performing the passive
      extraction of the gel with a saturated MALDI matrix solution. During the
      extraction period, the matrix is allowed to crystallize, forming a suspension in
      solution. Protein that elutes from the gel has a chance to cocrystallize with the
      matrix that can be retrieved for MALDI-MS analysis. This method of "capturing"
      eluted protein into matrix crystals is sensitive to 1 pmol of recombinant mouse
      leptin protein (16 kDa) loaded onto SDS-PAGE gels and can be used for proteins as
      large as 70 kDa. Our strategy has particular application to the characterization
      of endogenous forms of mature proteins from SDS-PAGE gels.

PMID- 9177687
TI  - A flow cytometric assay for lysosomal glucocerebrosidase.
AB  - A flow cytometric assay is described for the determination of glucocerebrosidase
      (GC) activity using fluorescein di-beta-glucopyranoside (FDGlu). Fluorescent
      product is formed upon intracellular hydrolysis of FDGlu and is measured in the
      FL1 channel of a flow cytometer. We show that the assay is specific for lysosomal
      beta-glucosidase or glucocerebrosidase (1) by concentration-dependent inhibition
      of GC activity by conditurol-beta-epoxide (CBE), a specific irreversible
      inhibitor; (2) by the absence of activity in fibroblasts isolated from patients
      with Gaucher disease; (3) correction of the biochemical Gaucher phenotype in
      these cells is detectable following gene transfer and can be inhibited by CBE;
      (4) murine fibroblasts transfected with the human GC cDNA and expressing 1.5- to
      2.5-fold higher levels of human GC in in vitro assays can be distinguished from
      nontransfected cells in mixing experiments; and (5) preincubation of GC
      expressing cells with the lysosomotropic compound chloroquine leads to a loss of
      the GC-mediated increase in fluorescence supporting lysosomal localization of the
      FDGlu hydrolyzing enzyme. This flow cytometric GC assay will be useful for
      monitoring GC activity at the single cell level and can be used for monitoring
      the efficacy of Gaucher patient treatments such as enzyme supplementation and
      gene therapy. Finally, our findings suggest that other lysosomal enzymes can be
      measured in this way using alternate fluorescein derivatives.

PMID- 9177688
TI  - Method for the collection and assay of volatile organic compounds in breath.
AB  - Breath testing for volatile organic compounds (VOCs) provides an intrinsically
      safe method for investigating human metabolism. An improved breath-collecting
      apparatus (BCA) is described which was acceptable to patients, simple to use,
      highly sensitive, and free from chemical contamination. VOCs in 10.0 L alveolar
      breath and 10.0 L room air were collected onto adsorptive traps. Using automated
      instrumentation, VOCs were thermally desorbed and assayed by gas
      chromatography/mass spectroscopy. Twenty normal volunteers were studied, and the
      alveolar gradient (concentration in breath minus concentration in air) was
      determined for the most abundant VOCs. A total of 1259 VOCs were observed and
      tentatively identified in the breath of normal subjects. The mean alveolar
      gradients were positive in 461 VOCs and negative in 798 VOCs. The method provided
      a sensitive and convenient assay for breath VOCs and permitted tentative
      determination of their origin from either inside or outside the body.

PMID- 9177689
TI  - Use of thermostable and Escherichia coli RNase H in RNA mapping studies.
AB  - A recently introduced thermostable RNase H was tested to determine its
      effectiveness in RNase H mapping reactions. Procedures are described which should
      have general use with both the thermostable and the Escherichia coli RNase H
      enzymes. Using the thermostable RNase H at higher temperatures extends the range
      of oligodeoxyribonucleotide/RNA combinations that yield satisfactory results.
      Northern blot analyses of total RNA was used to demonstrate that native RNAs can
      be analyzed by oligodeoxyribonucleotide directed RNase H digestion with minimal
      sample processing as long as care is taken to maintain thermal stringency both
      during reaction assembly and termination. Increased thermal stringency allows for
      higher DNA concentrations to ensure complete site-specific digestion of target
      RNAs or to permit simultaneous cleavage with multiple oligodeoxyribonucleotides.
      Partial digests can also be controlled by manipulating oligodeoxyribonucleotide
      concentrations. In addition, the thermostable RNase H was shown to be active at
      magnesium ion concentrations as low as 0.1 mM. This allows for optimization of
      Mg2+ effects on overall sample integrity and DNA/RNA interactions over at least a
      20-fold range (2.0-0.1 mM).

PMID- 9177690
TI  - Numerical isotopomer analysis: estimation of metabolic activity.
AB  - The use of stable isotopes to analyze intracellular metabolism is a powerful
      technique because of the wealth of information contained in the distribution of
      isotopes in key metabolites. We present a new numerical method of using
      measurements of isotope isomer (isotopomer) distributions to calculate the fluxes
      through a biochemical reaction network. Nuclear magnetic resonance (NMR) and/or
      mass spectroscopy can quantify the isotopomers which result from the metabolism
      of an isotopically enriched substrate. These data can be analyzed via a numerical
      model of the metabolic network which uses atom-mapping matrices to simplify model
      construction. The atom-mapping matrices describe the transfer of atoms from
      reactant to product and the resulting isoopomer balance equations are compact and
      intuitive. These equations are solved iteratively to determine the unknown
      intracellular fluxes. Results from the numerical method agreed with an analytical
      solution developed for the analysis of the tricarboxylic acid cycle in perfused
      hearts.

PMID- 9177691
TI  - High-resolution reversed-phase high-performance liquid chromatography analysis of
      polyamines and their monoacetyl conjugates by fluorescence detection after
      derivatization with N-hydroxysuccinimidyl 6-quinolinyl carbamate.
AB  - A highly sensitive, accurate, and reproducible HPLC method for the determination
      of all natural polyamines and their monoacetyl conjugates is described. The
      presented method is based on precolumn derivatization with N-hydroxysuccinimidyl
      6-quinolinyl carbamate (HSQC) followed by C18-HPLC separation using a ternary
      gradient and fluorescence detection (lambda Ex = 248 nm, lambda Em = 398 nm). The
      derivatives of the four main polyamines (putrescine, cadaverine, spermidine, and
      spermine) and the internal standard were synthesized on a preparative scale and
      characterized, especially with respect to their molar absorptivities and
      fluorescence quantum yields. The limits of detection of the highly stable
      derivatives ranged from 30 to 130 fmol (injection volume 10 microliters) for
      putrescine and N-acetylcadaverine, respectively (signal to noise ratio = 10),
      with excellent linearity within the range from 1 to 100 microM. High
      reproducibility for both retention times and peak areas, with coefficients of
      variation ranging from 0.14 to 0.88% and from 1.83 to 3.80%, respectively, were
      achieved. Provided that deproteinization of the samples was carried out
      immediately, recoveries of the analytes from homogenates of pancreatic cancer
      xenografts were high and reproducible. The optimized method was applied to the
      determination of the polyamine content of cultured pancreatic cancer cells and of
      tissue from colorectal adenocarcinoma, proving precise and reproducible
      quantification in these complex biological matrices.

PMID- 9177692
TI  - Capillary electrophoresis assay for ubiquitin carboxyl-terminal hydrolases with
      chemically synthesized ubiquitin-valine as substrate.
AB  - Ubiquitin is expressed in eukaryotic cells as precursors, fused via its carboxyl
      terminus either to other ubiquitin sequences in linear polyubiquitin arrays or to
      specific ribosomal proteins. In some of the polyubiquitin fusions a single amino
      acid (e.g., valine in humans) is attached to the carboxyl terminus. These gene
      products are rapidly (probably cotranslationally) cleaved by ubiquitin carboxyl
      terminal hydrolase (UCH) enzymes; therefore, although ubiquitin precursors are
      suitable substrates for assays of UCH activity, they are difficult to isolate
      from nucleated cells. While the recombinant approach allows the production of
      ubiquitin precursors in prokaryotic cells (which do not contain the ubiquitin
      system), proteins produced in this manner require purification and may also be
      susceptible to modification by bacterial enzymes, e.g., adventitious proteolysis.
      As an alternative we have chemically synthesized human ubiquitin-valine. In the
      assay described here the cleavage of ubiquitin-valine to ubiquitin (77 and 76
      residue proteins, respectively) by a purified recombinant Drosophila UCH was
      monitored by capillary electrophoresis. Mass spectrometry verified the precise
      cleavage of ubiquitin-valine, confirming that this synthetic protein is a UCH
      substrate. Synthetic ubiquitin-valine may serve as a generic substrate for UCHs
      allowing the purification and identification of new members of this enzyme
      family.

PMID- 9177693
TI  - Colloidal silver staining of electroblotted proteins for high sensitivity peptide
      mapping by liquid chromatography-electrospray ionization tandem mass
      spectrometry.
AB  - Mass spectrometric techniques for the identification of proteins either by amino
      acid sequencing or by correlation of mass spectral data with sequence databases
      are becoming increasingly sensitive and are rapidly approaching the limit of
      detection achieved by the staining of proteins in gels or, after electroblotting,
      on membranes. Here we present a technique for the sensitive staining of proteins
      electroblotted onto nitrocellulose or polyvinylidene difluoride membranes and
      enzymatic cleavage conditions for such proteins to achieve optimal recovery of
      peptides. The technique is based on the deposition of colloidal silver on the
      membrane-bound proteins. Peptide mixtures generated by proteolysis on the
      membrane were recovered at high yields and were compatible with analysis by
      reverse-phase chromatography and on-line electrospray ionization mass
      spectrometry. This simple and rapid colloidal silver staining procedure allowed
      the visualization of less than 5 ng of protein in a band and thus approached the
      sensitivity of silver staining in gels. We demonstrate that this method allows
      the detection of subpicomole amounts of electroblotted proteins and their
      identification by high-performance liquid chromatography-electrospray ionization
      tandem mass spectrometry.

PMID- 9177694
TI  - The structure of Silurus asotus (catfish) roe lectin (SAL): identification of a
      noncovalent trimer by mass spectrometry and analytical ultracentrifugation.
AB  - We identified a noncovalent trimer of Sirurus asotus roe lectin (SAL) at Mr
      95,362 along with its monomer at M(r) 31,750 by electrospray ionization mass
      spectrometry when SAL was dissolved in 0.5% acetic acid, sprayed into the ion
      source with methanol as a sheath liquid, and desolvated at 75 degrees C in a
      heated capillary column. The molecular weight of SAL, determined by the
      sedimentation equilibrium method, was 95,200 and the sedimentation coefficient
      (S20,w) of SAL in water was 5.58. SAL existed as a noncovalent trimer in solution
      and showed the ability to agglutinate rabbit erythrocytes. SAL showed three peaks
      (sal 1, sal 2, and sal 3) by C8 reverse-phase HPLC, and these appeared to be a
      monomer, a dimer, and a trimer, respectively, by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry, sal 1 and sal 2 were shown to have a
      structure interchangeable with that of sal 3 in water.

PMID- 9177695
TI  - A tyrosine kinase assay using reverse-phase high-performance liquid
      chromatography.
AB  - Reverse-phase HPLC can be used as a very precise and accurate routine assay for
      peptide phosphorylation by protein kinases that has advantages over other
      methods. In particular, peptides with native amino acid sequences can be used
      without the need for radioisotopes. However, reaction conditions that are
      employed can often present difficulties in recovery and quantitation of phospho-
      and apo-peptides. Two general problems were encountered; First, variation in the
      retention times of peptides and an increasing width of the injection front which
      can interfere with quantitation both resulted from repeated sample injections.
      These were caused mostly by the presence of carrier bovine serum albumin used to
      reduce loss of peptides during the reaction and by high concentrations of ATP
      used to study the kinetics of enzyme catalyzed reactions. These problems were
      solved by regular washing of the reverse-phase column, thus allowing a broad
      range of peptide and ATP concentrations to be used. Second, the stability of
      peptides used in the assay was affected by dithiothreitol in combination with
      manganese. The former is a common reagent of kinase purifications and the latter
      is often the metal cofactor used in kinase reactions. Minimizing the
      concentration of dithiothreitol or using magnesium resolved these difficulties.
      Consideration of these factors is therefore important when using reverse-phase
      HPLC to monitor peptide phosphorylation in protein tyrosine kinase assays.

PMID- 9177696
TI  - Complete removal and exchange of sodium dodecyl sulfate bound to soluble and
      membrane proteins and restoration of their activities, using ceramic
      hydroxyapatite chromatography.
AB  - Up to now, removal of sodium dodecyl sulfate (SDS) from proteins in terms of
      restoration of their activity was an unsolved problem. A general procedure using
      ceramic hydroxyapatite (HAP) chromatography was developed for the complete
      removal of SDS bound to soluble or membrane proteins. This procedure involves (i)
      the binding of the SDS-protein complexes onto the ceramic hydroxyapatite column,
      (ii) extensive washing of bound proteins with phosphate buffer containing a mild
      detergent to exchange SDS, (iii) elution of the retained protein by increasing
      the phosphate concentration. Using this approach, complete exchange of [35S]SDS
      into a nonionic detergent such as dodecyl maltoside was achieved with a 90-100%
      protein recovery. The efficiency of protein-bound SDS removal is very likely due
      to the combined effect of phosphate ions and the hydrophobic tail of nonionic
      detergent: acting together, they are able to displace SDS molecules from their
      protein-binding sites. The advantages of this HAP-mediated SDS removal method
      include high efficiency, rapidity, simplicity and general applicability to a wide
      variety of detergents and soluble or membrane proteins. Of utmost importance, SDS
      treated P-glycoprotein, glutamate dehydrogenase, and lysozyme fully recovered
      their enzymatic activities after HAP chromatography, including lysozyme
      electroeluted from SDS-polyacrylamide gel electrophoresis. This demonstrates that
      reactivation of SDS-treated protein can be achieved, provided that SDS is
      completely removed under mild conditions.

PMID- 9177697
TI  - A high-performance liquid chromatography-electrospray-tandem mass spectrometry
      analysis of cortisol and metabolites in placental perfusate.
AB  - A reversed-phase high-performance liquid chromatography-electrospray-tandem mass
      spectrometry assay (HPLC-ESI-MS/MS) was developed to quantitate cortisol,
      cortisone, 20 alpha- and beta-dihydrocortisol, 20 alpha- and beta
      dihydrocortisone, tetrahydrocortisol, and tetrahydrocortisone. The technique was
      used to analyze perfusate from the isolated human placental lobule for cortisol
      and its metabolites. Analytes were prepared from the perfusion medium using C18
      solid-phase extraction cartridges. The internal standard for the analyses was 6
      alpha-methylprednisolone. Chromatography was performed on a Novapak C18 column at
      ambient temperature using 53% methanol and 47% 10 mM ammonium formate buffer (pH
      4.0) as mobile phase, at a flow rate of 80 microL/min. A PE-SCIEX API III triple
      quadrupole instrument was used for mass spectrometric detection. An ionspray
      (pneumatically assisted electrospray) interface was used in negative and positive
      ionization mode. The assay was linear over the range 100-2000 micrograms/L for
      each analyte. The instrumental limit of detection was 50 pg. Assay imprecision at
      400 and 800 micrograms/L was < or = 10% (total coefficient of variation).
      Accuracy ranged between 83.2% for 20 beta-dihydrocortisone to 102.6% for
      cortisone. Recovery of 1000 micrograms/L analyte ranged from 91.3% for cortisone
      to 109.7% for tetrahydrocortisol.

PMID- 9177698
TI  - Synthesis and characterization of highly sensitive heparin probes for detection
      of heparin-binding proteins.
AB  - Three labeled heparin species were synthesized as probes for heparin-binding
      protein detection. Heparin conjugated with 5([4,6-dichlorotriazin-2
      yl]amino)fluorescein can be iodinated to a high specific activity. This probe
      specifically detected 40 pg histone on a dot blot without affinity purification.
      Heparin biotinylated on its naturally occurring primary amino groups also
      detected known heparin-binding proteins in a specific manner. This probe detected
      lower amounts of collagen I and basic fibroblast growth factor on nitrocellulose
      membranes than did the iodinated probe, with comparable detection times. To
      create more attachment sites for biotin, we covalently attached amino groups to
      the hydroxyl groups of heparin using 3-bromopropylamine hydrobromide. After
      biotinylation, the amino-rich probe detected heparin-binding proteins at the same
      or higher sensitivity as the biotinylated native heparin probe, using 100-fold
      less probe and much shorter detection times. This method of labeling is generally
      applicable to other polysaccharides, and would be useful when the amount of
      ligand is limited. We show that these three probes detect essentially the same
      spectrum of proteins in detergent extract of smooth muscle cell plasma membrane,
      and expect them to be useful probes for detection of cell-surface heparin
      receptors.

PMID- 9177699
TI  - Preparative purification of tetraantennary oligosaccharides from human asialyl
      orosomucoid.
AB  - An approach to isolate micromole quantities of tetraantennary oligosaccharides
      from human orosomucoid is presented. The N-linked oligosaccharides from 500 mg of
      the glycoprotein were released enzymatically, desialylated, and isolated free of
      protein using ion exchange chromatography. The pooled oligosaccharides were
      converted into oligosaccharide glycosylamines by reaction with ammonium
      bicarbonate then coupled to BOC-tyrosine to prepare tyrosinamide
      oligosaccharides. These were resolved on semipreparative RP-HPLC to recover
      micromole quantities of six purified tyrosinamide oligosaccharides. The
      oligosaccharide structures were elucidated by a combination of high-field proton
      NMR and matrix-assisted time of flight mass spectrometry and included
      biantennary, triantennary, monofucosylated triantennary, tetraantennary,
      monofucosylated tetraantennary, and a tetraantennary containing a single
      polylactosamine extension. Edman degradation was utilized to reverse the
      tyrosinamide oligosaccharide derivatization leading to the generation of reducing
      oligosaccharides. These were used to characterize the elution profile of asialyl
      orosomucoid oligosaccharides on high pH anion exchange chromatography. This
      application of tyrosinamide derivatization has allowed for the first time the
      complete resolution of the complex oligosaccharide mixture from orosomucoid on a
      semipreparative scale in a single chromatogram and provide the first NMR
      characterization of polylactosamine tetraantennary oligosaccharide from this
      substrate. This study demonstrates the broad utility of the tyrosinamide
      derivatization to develop oligosaccharide libraries useful for probing the
      biological functions of glycosylation.

PMID- 9177700
TI  - A matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      approach to identify the origin of the glycan heterogeneity of diptericin, an O
      glycosylated antibacterial peptide from insects.
AB  - In a previous study, electrospray ionization mass spectrometry was used to
      analyze the structure of the O-glycopeptide diptericin, an antibacterial peptide
      from the fleshfly Phormia terranovae. Several glycoforms of diptericin differing
      in the length of their oligosaccharide chains were present at the final stage of
      purification. In order to determine the origin of this glycan heterogeneity, we
      analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) the relative abundance of the different diptericin glycoforms in fractions
      obtained after each purification step, and directly in the hemolymph and in the
      fat body which produces diptericin. MALDI-MS clearly shows that the purification
      procedure had no effect on the O-linked oligosaccharide chains of diptericin,
      suggesting that diptericin is synthesized as a family of heterogeneous
      glycopeptides. In addition, in these experiments, differential mapping by MALDI
      MS of the hemolymph and fat body tissue from bacteria-challenged and naive larvae
      allowed us to detect induced or repressed molecules which may be involved in the
      immune response of P. terranovae.

PMID- 9177701
TI  - A radioactive binding assay for inhibitors of trkA kinase.
AB  - The high-affinity receptor for nerve growth factor (NGF), trkA, is a receptor
      linked tyrosine kinase. The binding of NGF to trkA, depending on the context of
      its environment, can cause beneficial or deleterious responses in the target
      cells. For example, the activation of trkA in sympathetic and sensory neurons
      causes the subsequent survival and differentiation of these cells. On the other
      hand, the activation of trkA by NGF in other cells has been implicated in several
      pathologies including inflammation-induced hyperalgesia and several cancers. A
      radioactive binding assay to evaluate inhibitors of the kinase domain of trkA has
      been developed and validated. The assay monitors the specific binding of an
      inhibitor of trkA kinase activity, the indolocarbazole K-252a, to the trkA
      receptor. [3H]K-252a binds with high affinity to one site on the cytoplasmic
      kinase domain of the trkA receptor. Binding is saturable and reversible with a
      dissociation constant (Kd) of 1.5 nM. The binding assay has been used in
      competition binding experiments to determine the inhibition constants for other
      indolocarbazole compounds. The IC50 values for compounds obtained in the binding
      assay correlate very well with the IC50 values obtained in an enzyme-linked
      immunosorbent assay for trkA tyrosine kinase activity.

PMID- 9177702
TI  - On the interaction between a bactericidal antibody and a PorA epitope of
      Neisseria meningitidis in outer membrane vesicles: a competitive fluorescence
      polarization immunoassay.
AB  - This paper describes a method for determining the affinity constant (Ka) of the
      binding between an antibody Fab fragment and a membrane-embedded protein epitope
      under equilibrium conditions. Monoclonal antibody MN12H2, directed against outer
      membrane protein PorA of Neisseria meningitidis, is used in a competitive
      fluorescence polarization assay with a cyclic peptide-fluorescein conjugate as a
      tracer antigen. Displacement experiments with PorA-containing and PorA-deficient
      meningococcal outer membrane vesicles revealed highly specific binding of MN12H2
      Fab to the membrane-embedded PorA P1.16 epitope with Ka of 1.5 x 10(8) M-1.

PMID- 9177703
TI  - Enzymatic assay of beta-lactamase using circular dichroism spectropolarimetry.
AB  - A method for measuring the rates of enzymatic hydrolysis of beta-lactam
      antibiotics based on circular dichroism spectropolarimetry is described.
      Unhydrolyzed beta-lactam antibiotics have high molar ellipticities, but the
      hydrolyzed compounds are circular dichroism (CD) inactive in the case of penams
      or have significantly different CD spectra in the case of cephems. By measuring
      CD at constant wavelength as a function of time for reaction mixtures containing
      beta-lactamase and beta-lactam antibiotics, rates of hydrolysis and steady-state
      enzyme kinetic constants can be derived. The method was applied to measurement of
      a wide range of enzymatic reaction constants for wild-type and four mutant RTEM-1
      beta-lactamases. Compared to the commonly employed assay based on ultraviolet
      spectroscopy, the new method offers several advantages. These include the ability
      to measure larger enzymatic Michaelis-Menten constants, less interference from
      high concentrations of beta-lactamase, higher sensitivity, and potentially less
      interference from other uv-absorbing components of complex reaction mixtures.

PMID- 9177704
TI  - Detection of infrequent and multiple K-ras mutations in human tumors and tumor
      adjacent tissues.
AB  - A sensitive method was developed and applied to examine the distribution of K-ras
      gene mutations in histologically differing areas of lung tissues obtained from
      lung cancer patients. This method, which combines polymerase chain reaction
      (PCR), mutation allele enrichment (MAE), and denaturing gradient gel
      electrophoresis (DGGE), allows detection of one K-ras mutant allele present in
      10(4) to 10(5) wild-type alleles. It was applied to analyze mutations in codon 12
      of the K-ras gene in 43 tissue sites microdissected from paraffin-embedded
      sections obtained from 8 archival cases of lung cancer, all previously shown to
      have codon 12 K-ras mutations by direct sequencing. In four cases, mutations were
      detected only in the tumor, while in the other four cases, the same mutations
      were also found in tissues adjacent to tumors, using the MAE + DGGE method. No
      mutations were detected among normal-appearing cells in areas distant from the
      tumors in any of the cases studied. These findings demonstrate that K-ras
      mutations can be detected at low frequencies in normal-appearing cells from
      tissues adjacent to the tumor in some lung cancer cases. In addition, this
      approach also allowed detection of multiple mutations in colorectal tissues
      obtained from colorectal cancer patients. Thus, the MAE + DGGE method may be
      applicable to study of K-ras mutations in premalignant or morphologically
      suspicious lesions in bronchial mucosa or other types of human cancer.

PMID- 9177705
TI  - Quantitative measurement of superoxide generation using the spin trap 5
      (diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide.
AB  - Measurement and quantitation of superoxide by electron paramagnetic resonance
      (EPR) using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) have been
      limited by the short half-life of the superoxide adduct DMPO-OOH (approximately
      50 s at pH 7). Recently a beta-phosphorylated nitrone, 5-(diethoxyphosphoryl)-5
      methyl-1-pyrroline-N-oxide (DEPMPO), was developed and reported to form a more
      stable superoxide adduct with a half-life of approximately 15 min. We evaluated
      the use of DEPMPO for quantitative measurement of superoxide in chemical and
      biochemical systems. To estimate the efficiency of trapping, EPR oximetry was
      used to measure oxygen consumption and the intensity of the DEPMPO-OOH signal to
      measure superoxide generation and adduct decay. With the superoxide-generating
      systems, riboflavin/light and xanthine/xanthine oxidase, DEPMPO trapped
      approximately 65% of the superoxide produced. The efficiency of superoxide
      trapping by DEPMPO was compared to the commonly used cytochrome c reduction
      method. When superoxide production was > 20 microM, cytochrome c detected
      approximately 100% of the superoxide produced, while DEPMPO trapped 60 to 70%.
      However, EPR detection with DEPMPO was 40-fold more sensitive than cytochrome c.
      Thus, DEPMPO is an efficient spin trap which enables specific and sensitive
      detection and quantitation of superoxide generation.

PMID- 9177706
TI  - Efficient immobilization of proteins by modification of plate surface with
      polystyrene derivatives.
AB  - Immobilization of proteins on microplate wells by simple adsorption (e.g., for
      ELISA) is convenient, but it can be inefficient, especially if proteins are
      hydrophilic or small in size. This problem was alleviated by the use of
      polyvinylbenzyl lactonoylamide (PVLA). PVLA is strongly adsorbed to the
      hydrophobic well surface, and its lactonamide part can be oxidized with periodate
      to generate aldehydo groups. Proteins are then immobilized covalently to the
      aldehydo groups by reductive amination under mild conditions. Using this method,
      henceforth termed the PVLA method, alkaline phosphatase (AP) was immobilized to
      microplates six- to sevenfold greater than by simple adsorption (as measured by
      activity). Similarly, the activity of immobilized mannose-binding protein A (MBP
      A) was 4- to 8-fold higher by the PVLA method than by simple adsorption. The PVLA
      coated plates needed as little as 200 ng of MBP-A per well to have a sufficient
      amount of MBP-A immobilized for the measurement of binding of 125I-labeled
      mannosylated bovine serum albumin (125I-Man-BSA), but unmodified plates required
      as much as 20 micrograms/well MBP-A to obtain the same response. Recommended
      conditions for the PVLA method are 40 microliters of 2 mg/ml of PVLA for coating,
      1 mM NaIO4 for the generation of the aldehydo groups, and a 2-h reductive
      amination at 37 degrees C between pH 8 and 9 for the protein ligation.

PMID- 9177707
TI  - An assay method for nitric oxide-related compounds in whole blood.
AB  - Recent evidence suggests that nitric oxide (NO) generated in vivo will be
      converted into the forms of nitrite/nitrate, nitrosyl hemoproteins, nitrosyl
      metal complexes, and S-nitroso-compounds in the circulation. Nitrosothiols have
      also been reported to be relatively stable metabolites with micromolar levels in
      plasma. We hypothesized, therefore, that the determinations of all the NO-related
      compounds in blood would be of diagnostic significance. The assay method
      described here consists of the thermolysis of all the NO-related compounds in
      whole blood and the detection of resulting nitrate by fluorometry or
      chemiluminescence after an enzymatic reduction. S-Nitroso-albumin and nitrosyl
      hemoglobin can be easily thermolysed to nitrate, and relatively stable S-nitroso
      glutathione is also degraded to nitrate in the presence of blood constituents
      with high molecular mass (above 30 kDa). Concentrations of NO-related compounds
      in blood from healthy human as well as control or lipopolysaccharide-stimulated
      rats were determined. We found that membrane-bound NO which showed the augmented
      levels under the pathophysiological states could also be detected. Together with
      electron spin resonance spectra, our data indicate that the fraction of NO
      diffused and metabolized within red cells and the other NO-metabolites in plasma
      such as nitrite/nitrate and S-nitroso-compounds, both of which can reflect NO
      production in vivo, would be recovered and detected quantitatively by this
      method.

PMID- 9177708
TI  - Assay method for femtogram order of Ca2+, Mg(2+)-dependent endonuclease.
AB  - A sensitive method for the assay of Ca2+, Mg(2+)-dependent endonuclease was
      developed. The assay procedure is composed of two parts: (i) microscale
      endonuclease digestion of highly polymerized calf thymus DNA and (ii) the
      quantification of DNA breaks by measuring the activation of poly(ADP-ribose)
      polymerase, which is known to be activated proportionally to the number of nicks
      and ends of DNA added in the reaction mixture. This method was approximately
      10(5)-fold more sensitive than a conventional DNase assay detecting acid-soluble
      DNA formation and, thus, the activity of 20 to 100 fg of purified bull seminal
      Ca2+, Mg(2+)-dependent endonuclease could be reliably measured. Ca2+ and Mg2+
      requirements and the response to histone H2B of the endonuclease were also
      demonstrated by this method. Using this method, the assay of a very small amounts
      of Ca2+, Mg(2+)-dependent endonuclease in crude extracts of calf thymus chromatin
      was possible. This method may be applied to other types of endonucleases by
      modifying the mixture for endonuclease reaction.

PMID- 9177709
TI  - Positional isomers of monopegylated interferon alpha-2a: isolation,
      characterization, and biological activity.
AB  - The success of recombinant interferon alpha in the clinic in part is limited by
      two properties of the protein: short serum half-life and immunogenicity. To
      improve these properties, interferon alpha-2a was conjugated with polyethylene
      glycol (PEG-5000). A homogeneous preparation of monopegylated interferon alpha-2a
      was subjected to vigorous analytical and activity characterization. A newly
      developed ampholyte-free chromatofocussing-like cation-exchange HPLC method
      utilizing a sulfopropyl resin was used to separate the monopegylated protein into
      11 species. Peptide mapping, sequencing, and mass spectrometric analyses
      indicated that these species are positional isomers where each isomer represents
      a single polymer molecule conjugated to one specific lysine residue. No species
      with a modification at the amino terminus was observed. All 11 isomers show
      antiviral and antiproliferative activities in the same range as the parent
      monopegylated interferon alpha-2a.

PMID- 9177710
TI  - Misinterpretation of the biological activity of cytokine-containing preparations
      attributable to unrecognized interacting components.

PMID- 9177711
TI  - Automated microfluorometric determination of DNA in recombinant adenoviral
      samples.

PMID- 9177712
TI  - Targeted deletion of a GA tract by S1 nuclease.

PMID- 9177713
TI  - A novel approach to 14C label N-linked oligosaccharides.

PMID- 9177714
TI  - Vectors for expressing proteins at the amino-terminus of an activation domain for
      use in the yeast two-hybrid system.

PMID- 9177715
TI  - The minimum size that a protein-free ADP-ribose chain requires to precipitate in
      20% (w/v) trichloroacetic acid is 14 units.

PMID- 9177716
TI  - A single competitive reverse transcriptase-polymerase chain reaction assay to
      measure inducible nitric oxide synthase gene expression in both human and rat.

PMID- 9177717
TI  - Utilization of the freeze-drying method in the preparation of biologically
      active, intact RNA from hard frozen tissues of human prostate.

PMID- 9177718
TI  - Synthesis of [9-14C]nonanoic acid via 2-thienyl(14CH3)(cyano)cuprate and its
      oxidation by newborn piglet muscle strips.
AB  - To determine if newborn piglet muscle could oxidize propionyl-CoA formed by
      catabolism of odd-chain fatty acids, an odd-chain fatty acid labeled in the
      terminal three carbons was needed. The synthetic scheme described is based upon
      the displacement of a primary alkyl iodide, ethyl 8-iodooctanoate, by a
      [14C]methyl group via an activated 2-thienyl(14CHa)(cyano)cuprate intermediate,
      forming ethyl [9-14C]nonanoate. Ethyl [9-14C]nonanoate was hydrolyzed in 6 N KOH
      and [9-14C]nonanoic acid recovered by ion-exchange chromatography. The yield of
      [9-14C]nonanoic acid was 40%, based on the initial amount of [14C]methyl iodide.
      The cuprate and other precursors were commercially available or readily
      synthesized from available precursors. Mass spectroscopy of commercial and
      synthesized nonradioactive nonanoate determined an m/z of 159 for the product
      molecular ion, as expected. The 14C-labeled product phenacyl ester was found to
      cochromatograph in a C-18 reverse-phase HPLC system with similarly derivatized
      commercially obtained nonanoic acid. The synthesis should be generally applicable
      to labeling of compounds by displacement of primary alkyl iodides, where other
      reactive groups (e.g., carboxylic acid), if present, can be protected (e.g.,
      converted to an ester). Muscle strips isolated from the triceps muscle of newborn
      piglets oxidized [9-14C]nonanoic acid to 14CO2. Newborn piglet muscle can oxidize
      propionyl-CoA produced during odd-chain fatty acid oxidation.

PMID- 9177719
TI  - Structural characterization of peptidoglycan muropeptides by matrix-assisted
      laser desorption ionization mass spectrometry and postsource decay analysis.
AB  - In this study we report the development of matrix-assisted laser desorption
      ionization mass spectrometry (MALDI-MS)-based methods for the structural
      characterization of muropeptides derived from peptidoglycan. Prior to analysis,
      peptidoglycan samples were subjected to enzymatic digestion with muramidase and
      the resulting muropeptides were purified by HPLC. A new matrix, 5-chloro-2
      mercaptobenzothiazole, was employed for the MALDI-MS analysis. The results have
      demonstrated that sub-picomole to femtomole detection can be achieved in both
      positive mode and negative mode, allowing unambiguous determination of the
      molecular masses of monomeric and oligomeric muropeptides. Structural information
      from monomeric muropeptides was obtained by further postsource decay (PSD)
      analysis. Fragmentation patterns in positive mode and negative mode PSD were
      complementary for the elucidation of the peptide chain sequence. Lysostaphin
      digestion was also incorporated with MALDI mass mapping analysis for
      determination of peptide chain cross-linking patterns of muropeptide oligomers
      from Staphylococcus aureus strains.

PMID- 9177720
TI  - Characterization of the structural difference between active and inactive forms
      of the Ras protein by chemical modification followed by mass spectrometric
      peptide mapping.
AB  - Ras is one of the guanosine triphosphate (GTP) binding proteins that plays a
      significant role in signaling events of cell growth and differentiation. It can
      exist in two states: guanosine diphosphate (GDP)-bound from (Ras.GDP; inactive)
      and GTP-bound form (Ras.GTP; active). This paper discusses the difference in
      tertiary structure between the active and inactive forms using the combination of
      chemical modification and mass spectrometry. This difference can be clearly
      recognized in the presence of a target protein. Raf-1 RBD (Raf-1 Ras-binding
      domain), as differing glycinamidation of carboxyl groups. It was possible to
      observe the difference between these two states using several hundred picomoles
      of sample. While it is true that it is difficult to obtain the whole picture of a
      protein by the combination of chemical modification and mass spectrometry, it is
      a promising approach for the characterization of surface structure using very
      small amounts of sample.

PMID- 9177721
TI  - Measurement of cytochrome P450 2E1 activity in rat tracheobronchial airways using
      high-performance liquid chromatography with electrochemical detection.
AB  - Cytochrome P450 2E1 catalyzes the metabolic activation of nitrosamines and
      haloalkenes to carcinogenic and cytotoxic derivatives; however, the regulation of
      this P450 isozyme is not well understood. Hydroxylation of p-nitrophenol to p
      nitrocatechol has been used as a marker of CYP2E1 activity, but currently
      available methodologies are not sufficiently sensitive to allow measurements in
      small tissue samples or in tissues with low activity such as lung. We describe
      here a method for measuring p-nitrocatechol formation using HPLC with
      electrochemical detection which is rapid and specific. It has a level of
      sensitivity (pmol) sufficient to monitor CYP2E1 activities in incubations
      containing as little as 10 micrograms microsomal protein prepared from airway
      subcompartments of the lung, a tissue with low and varying CYP2E1 activities
      among different parts of the airways.

PMID- 9177722
TI  - Fluorescence analysis of the labile iron pool of mammalian cells.
AB  - The labile iron pool (LIP) of cells constitutes a cytosolic fraction of iron
      which is accessible to permeant chelators and contains the cells' metabolically
      and catalytically reactive iron. LIP is maintained by a balanced movement of iron
      from extra- and intracellular sources. We describe here an approach for tracing
      LIP levels in living cells based on the fluorescent probe calcein (CA). This
      probe binds Fe(II) rapidly, stoichiometrically, and reversibly while forming
      fluorescence-quenched CA-Fe complexes. Cells are loaded with CA via its
      acetomethoxy precursor CA-AM, attaining 1-10 microM intracellular concentrations
      and retaining full viability. LIP is defined here operationally as the sum of
      "free" and CA-bound iron of the cell. The method for assessing LIP is based on
      the measurement of: (a) the total intracellular concentration of CA in CA-loaded
      cells ([CA]1), which is estimated from fluorimetric measurements of CA in a given
      suspension of cells, the number of cells, and the cell volume; (b) the
      intracellular [CA-Fe], the concentration of [CA] bound to metals (> 95% iron),
      which is assessed from the relative rise in fluorescence (delta F) elicited by
      addition of highly permeant and high-affinity binding chelators such as
      salicyladehyde-isonicotinoyl-hydrazone (SIH) and the value of [CA]1; and (c) the
      "free" cell iron concentration [Fe(II)], which is computed from the
      experimentally determined values of CA-Fe(II)'s dissociation constant (Kd) in
      various cell lines grown in suspension (Kd = 0.22 +/- 0.01 microM). The value of
      cellular LIP is defined as the sum of [CA-Fe] and [Fe]. It is derived from the
      experimental determination of [CA]1 and [CA-Fe] and from calculation of [Fe] by
      application of the mass law equation using the Kd value of [CA-Fe]. The estimated
      values of LIP for resting erythroid and myeloid cells are in the range of 0.2-1.5
      microM. The values varied commensurately with cell iron loads and iron chelator
      treatment. The method provides a simple, noninvasive tool for on-line monitoring
      of cytosolic iron under normal and abnormal conditions of cell iron supply and
      for assessing the dynamics of intracellular iron in living cells.

PMID- 9177723
TI  - Chemiluminescence-high-performance liquid chromatographic determination of tea
      catechin, (-)-epigallocatechin 3-gallate, at picomole levels in rat and human
      plasma.
AB  - A method of chemiluminescence detection-high-performance liquid chromatography
      (CL-HPLC) for the highly specific determination of tea catechin, (-)
      epigallocatechin 3-gallate (EGCg), present in rat and human plasma has been newly
      developed. The CL-HPLC system consists of reversed-phase HPLC and
      chemiluminescence detector, in which separated EGCg generates chemiluminescence
      at post column successively reacting with the following two chemiluminescence
      cocktails; 8.2 M acetaldehyde in 50 mM phosphate buffer (pH 7.4, contained 108 mg
      horseradish peroxidase/L) and 8.8 M hydrogen peroxide aqueous solution. The
      plasma EGCg was extracted by methanol. This method enables the detection of EGCg
      in the free form selectively at as low as 2 pmol with recovery of 84%. The EGCg
      concentration in fasted rat plasma was initially below the detection limit (< 2
      pmol/ml), but increased to maximum level (2284 pmol/ml plasma, 1047 ng/ml;
      calculated 0.012% of ingested EGCg) 30 min after a single oral supplementation of
      56 mg EGCg per rat. The EGCg concentration in fasted human plasma was also
      initially below the detection limit and increased to 341 pmol/ml (156 ng/ml;
      calculated 0.32% of ingested EGCg) at 60 min after a single oral intake of 97 mg
      EGCg per subject. The results indicated that tea catechin, EGCg, is absorbed from
      the digestive tract into the rat and human body and that the CL-HPLC method
      reported here should be a powerful tool for studying the metabolic fate and
      bioavailability of EGCg.

PMID- 9177724
TI  - Accurate topological comparison of two recombinant human growth hormones by
      optical surface plasmon resonance.
AB  - A strategy for the comparison of two recombinant derived human growth hormones (r
      hGH) has been developed using surface plasmon resonance (SPR). Statistical
      analysis was systematically used on the results obtained with several batches
      derived from two different Escherichia coli strains. Monoclonal antibodies (MAb)
      directed against four different domains in the tertiary structure of natural
      human growth hormone were used to compare the epitopic maps of the three (two
      recombinant and one natural) hGH by SPR analysis. Topological studies show the
      homogeneity of the epitopic maps of the three hGH. The kinetic parameters,
      association rate, and dissociation rate constants were also analyzed for the
      binding of each hGH batch to all MAbs. They were found to be homogeneous between
      the three hormones. Furthermore, the two r-hGH were compared by more classical
      approaches examining recognition of lactogenic or somatogenic receptors using,
      respectively, a bioassay of Nb2 cell proliferation and binding to rat liver
      microsomes. Specific bioactivities and IC50 values calculated in radioreceptor
      assays did not significantly differ between different r-hGH. The method was
      sensitive enough to show slight differences on koff value for one MAb (3C11)
      between (natural) hormone and two r-hGH. These differences are discussed in
      relation to previous observation made in the literature and the presence of
      isoforms in the natural product. The strategy developed here was very useful as a
      new tool to establish the equivalence of the two r-hGH.

PMID- 9177725
TI  - Oligosaccharide characterization and quantitation using 1-phenyl-3-methyl-5
      pyrazolone derivatization and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.
AB  - The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of monosaccharides,
      maltooligosaccharides, and oligosaccharides enzymatically released from
      asparagine-linked sites in ribonuclease B and fetuin have been investigated using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). Use of the matrix 2,6-dihydroxyacetophenone containing diammonium
      hydrogen citrate (DHAP/DAHC) resulted in predominance of protonated over sodiated
      pseudomolecular ions of PMP-derivatized oligosaccharides. By comparison, the
      matrices alpha-cyano-4-hydroxycinnamic acid and 2,5-dihydroxybenzoic acid
      resulted in predominantly sodiated pseudomolecular ions. In addition, tendencies
      for fragmentation of PMP-oligosaccharide derivatives were significantly lower
      with DHAP/DAHC which enabled meaningful data to be obtained in reflector mode,
      even for samples with high excipient levels. The relative magnitude of the ion
      signals for PMP-derivatized maltooligosaccharides and ribonuclease B
      oligosaccharides correlated well with the oligomer distribution apparent by HPLC.
      PMP-maltohexose was used as an internal standard to quantitate PMP
      oligosaccharides from ribonuclease B and asialofetuin in crude derivatization
      mixtures. A linear relationship was observed between the ratio of the intensities
      of pseudomolecualr ions and the amount of glycoprotein derivatized. The limit of
      detection for the major oligosaccharide of each protein was reached with ca. 3
      micrograms of glycoprotein but may be further enhanced by optimization of sample
      handling. PMP derivatives of sialylated fetuin oligosaccharides were readily
      detected as protonated pseudomolecular ions by linear mode analyses. By
      comparison, reflector mode analyses revealed substantially reduced magnitudes of
      protonated pseudomolecular ions and considerable post-source fragmentation of
      sialic acid residues. The PMP derivatives of fetuin oligosaccharides were also
      amenable to exoglycosidase treatment as shown by the mass shifts found upon
      treatment with sialidase.

PMID- 9177726
TI  - Quantitative gas chromatography-mass spectrometry isomer-specific measurement of
      hydroxy fatty acids in biological samples and food as a marker of lipid
      peroxidation.
AB  - We have developed a capillary gas chromatography-mass spectrometry method for the
      quantitative analysis of individual positional isomers of monohydroxy fatty acids
      derived from linoleic, arachidonic, eicosapentaenoic, or docosahexaenoic acid.
      Peroxidation of a particular polyunsaturated fatty acid results already in a
      complex mixture of positional isomers of hydroperoxy and hydroxy fatty acids.
      Catalytic hydrogenation of lipid extracts produces stable saturated hydroxy
      lipids from the complex mixtures typical of oxidized biological samples,
      simultaneously simplifying the analytical problem and eliminating oxidation
      artifacts. After saponification and methylation, monohydroxy fatty acid methyl
      esters are purified by solid-phase extraction and partially resolved using a CP
      Sil 19 column following on-column derivatization of the hydroxy groups with
      tetramethylammonium hydroxide. The resulting methoxy fatty acid methyl esters are
      subjected to electron impact mass spectroscopy. Two characteristic ions are
      produced for each positional isomer. Quantitative measurements were achieved by
      using odd chain C17 and C19 monohydroxy fatty acids as internal standards. The
      limit of detection of individual hydroxy fatty acid isomers is dependent on the
      total number of ions monitored. Monitoring 11 pairs of ions simultaneously gives
      limits of detection of 10 ng. Sensitivity is much higher by monitoring fewer ions
      and as little as 0.2 ng of a single isomer can be detected. The method has been
      applied for the quantitative analysis of hydroxy (plus hydroperoxy) fatty acids
      in plasma, adipose tissue, oils, and foods. To date over 1000 samples have been
      analyzed using the method described in this paper.

PMID- 9177727
TI  - Spontaneous oxidation of methionine: effect on the quantification of plasma
      methionine levels.
AB  - Plasma methionine (Met), methionine sulfoxide (MSO), and total Met concentrations
      were determined by reversed-phase chromatography and fluorescence detection after
      automated precolumn derivatization with an o-phthalic aldehyde mercaptoethanol
      reagent. Addition of pure, MSO-free L-Met to plasma samples resulted in the
      anticipated linear increase in plasma Met concentrations, but simultaneously
      effected a dose-dependent, linear increase in MSO levels. In contrast, the
      addition of pure L-MSO to plasma samples rendered linear calibration curves for
      MSO, while the Met concentration remained constant. A strong buffering effect
      against the spontaneous or hydrogen peroxide induced oxidation of Met to MSO was
      observed in plasma samples. This protective effect could be neutralized by
      preincubating the plasma samples with sodium azide. The addition of relatively
      low concentrations of red cell lysates to plasma samples, prior to hydrogen
      peroxide oxidation, strongly inhibited the conversion of Met to MSO. Plasma
      samples from 127 healthy female volunteers were analyzed: MSO concentrations
      (mean, 3.6 +/- 2.1 microM) exhibited a weak positive correlation (r = 0.352) with
      Met levels (mean, 21.3 +/- 6.1 microM) but, after the exclusion of two probable
      outliers from the data set, no correlation was observed. Our results suggest that
      plasma Met concentrations should be corrected for oxidative losses incurred
      during storage, sample processing and because of the action of a variety of in
      situ oxidants, present in plasma, in order to obtain a reliable estimate of the
      methionine status of an individual.

PMID- 9177728
TI  - Di-fluoresceinthiocarbamyl-insulin: a fluorescent substrate for the assay of
      protein disulfide oxidoreductase activity.
AB  - We have developed a novel method for the continuous assay of protein disulfide
      oxidoreductase activity using as substrate bovine pancreas insulin in which both
      N-terminal amino groups are chemically modified with fluorescein isothiocyanate.
      The reduction of intercatenary disulfide bonds of di-fluoresceinthiocarbamyl
      insulin with dithiothreitol initially lowers but subsequently enhances the
      emission intensity. In this biphasic kinetics, the rate of increase is sensitive
      enough for the estimation of Escherichia coli thioredoxin concentrations from 5
      nM (0.06 microgram/ml) to 500 nM (6 micrograms/ml). Neither changes of pH over a
      range of 6.2 to 8.4 nor neutral salts (K+, Mg2+, and Ca2+) at concentrations
      lower than 100 mM affect this simple reaction system. Moreover, the fluorometric
      method is functional for measuring the reductive capacity of Brassica napus
      protein disulfide isomerase. Hence, a highly reproducible and accurate one-state
      assay for protein disulfide oxidoreductase activity not only greatly improves the
      sensitivity compared to the commonly used turbidimetric assay but also represents
      a reliable alternative to assays based on accessory enzymes or radiolabeled
      substrates.

PMID- 9177729
TI  - Triple helix formation on plasmid DNA determined by a size-exclusion
      chromatographic method.
AB  - Triple-helix-forming oligodeoxynucleotides are receiving considerable attention
      due to their potential applications for the inhibition of specific genes in vivo.
      However, their development is impaired by the lack of triple helix formation
      under physiological conditions. It is thus crucial to be able to quantitatively
      assay triple helix formation of various oligodeoxynucleotides on different target
      sequences. Usual methods to detect triple helix formation are restricted under
      the experimental conditions that can be studied. In addition, quantitative
      techniques are limited. We present a novel method for rapid detection and
      quantification of triple helix formation between an oligodeoxynucleotide and a
      plasmid carrying a target sequence. The oligodeoxynucleotide was radiolabeled
      and, after incubation with the target plasmid, the unbound oligodeoxynucleotide
      was separated from the mixture of plasmids and plasmid-bound
      oligodeoxynucleotides by rapid gel filtration spun columns. The formation of a
      triple helix between a target plasmid and several oligodeoxynucleotides was
      demonstrated and compared. Temperature, sequence and ionic dependencies, and
      kinetics of association were analyzed. This new technique can be used under a
      variety of conditions and should allow the rapid determination of optimal
      conditions required for triple helix formation, as well as the easy selection of
      an oligodeoxynucleotide that specifically binds with the highest affinity to a
      target double-stranded sequence.

PMID- 9177730
TI  - Low-molecular-weight displacers for high-resolution protein separations.
AB  - The resolving power of displacement chromatography using low-molecular-weight
      displacers was investigated using a model mixture containing bovine and horse
      heart cytochrome c. The linear and nonlinear adsorption behavior of these two
      proteins was examined in cation-exchange chromatography and shown to be quite
      similar. Furthermore, an analysis of the dynamic affinity of these proteins
      indicated extremely similar affinities under displacement conditions. Despite the
      extreme similarities in the adsorption behavior, displacement chromatography
      using a protected amino acid displacer resulted in excellent separation of the
      proteins with both high yields and purity. These results indicate that
      displacement chromatography may be efficacious for a wide variety of difficult
      protein separation problems.

PMID- 9177731
TI  - Direct coating of poly(lys) or acetyl-thio-acetyl peptides to polystyrene: the
      effects in an enzyme-linked immunosorbent assay.
AB  - Direct adsorption of small peptides to polystyrene surfaces is often not
      satisfactory. Therefore, a simple and general coating procedure to improve the
      coating efficiency of small synthetic peptide antigens to polystyrene is
      described. In this study, the binding capacities of four small synthetic peptides
      N-terminally linked to various moieties during synthesis were compared to their
      parent counterparts in terms of the amount of peptide coat concentration required
      to achieve 50% of the maximum enzyme-linked immunosorbent assay signal.
      Elongation of a short epitope sequence by an N-terminal acetyl-thio-acetyl (Ata)
      group or a lysyl moiety resulted in an enormous reduction in peptide coat
      concentration for all tested peptides of net two to four orders of magnitude when
      corrected for chain elongation. The optimal length of the lysyl moiety depended
      on the length of the model peptide. Replacement of both extensions by analogues
      (i.e., Ata analogues and other basic amino acid residues in the case of the lysyl
      moiety) was possible without reducing their enhancing properties to a great
      extent. Additional experiments showed that a lysyl moiety consisting of a linear
      stretch of seven lysyl moiety consisting of a linear stretch of seven lysyl
      residues was more effective in comparison to a branched lysyl construct and could
      easily compete with the multiple antigen peptide approach.

PMID- 9177732
TI  - Kinetics of competitive binding with application to thrombin complexes.
AB  - The kinetics of competitive binding is treated analytically, allowing the rate
      constants to be determined accurately from simple experiments. The method is
      especially suited to situations where traditional approximations and numerical
      integration fail, e.g., when the dissociation constants are small or when the
      concentration of one receptor cannot be measured accurately. The method is
      applied to the competitive binding of hirudin to thrombin and anhydrothrombin and
      found to be accurate to a few parts in ten million. The fitted rate constants
      show that anhydrothrombin binds hirudin more weakly than thrombin, with a 2.6
      fold increase in its dissociation constant. The small relative difference in
      binding free energy (0.6 kcal/mol indicates that anhydrothrombin is structurally
      similar to thrombin.

PMID- 9177733
TI  - C-terminal incorporation of fluorogenic and affinity labels using wild-type and
      mutagenized carboxypeptidase Y.
AB  - The ability to carry out specific C-terminal modification or labeling of peptides
      and proteins has a broad range of applications. It is well established that this
      may be achieved by protease-catalyzed transacylation reactions and that
      carboxypeptidase Y (CPD-Y) is suitable for this due to its broad specificity and
      stability in the presence of denaturants. Furthermore, CPD-Y is characterized by
      a S'1 binding site that is open to solvent and, thus, capable of catalyzing a
      transpeptidation reaction with nucleophiles that extend beyond the perimeter of
      the active site. However, one major drawback with CPD-Y is that the yield of the
      reaction is highly dependent on the nature of the leaving group; e.g., with large
      apolar leaving groups the yield of the reaction does not exceed 15%. In the
      present publication it is demonstrated that mutants of CPD-Y, designed for low
      leaving group dependence, efficiently incorporate biocytin amide as well as a new
      fluorescent nucleophile, N'-Abz-Lysine amide (ablysin amide), into peptides and
      proteins.

PMID- 9177734
TI  - Chemical characterization of eumelanins with special emphasis on 5,6
      dihydroxyindole-2-carboxylic acid content and molecular size.
AB  - Mammalian melanins exist in two chemically distinct forms; the brown to black
      eumelanins and the yellow to reddish pheomelanins. Eumelanins are derived from
      copolymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2
      carboxylic acid (DHICA). Eumelanins can be quantified by HPLC analysis of the
      oxidation product pyrrole-2,3,5-tricarboxylic acid (PTCA) and by our
      spectrophotometric method (Sp.EM). We also developed a spectrophotometric method
      for assaying the total amount of eu- and pheomelanins by dissolving them in
      Soluene-350 (TM). In addition, we previously showed that Sp.EM/TM and PTCA/TM
      ratios are significant parameters in characterizing eumelanins produced in
      follicular melanocytes. The objectives of this study were (1) to clarify the
      significance of Sp.EM/TM and PTCA/TM ratios in synthetic eumelanins and (2) to
      apply these methods to characterizing natural eumelanins with various DHI/ DHICA
      ratios and molecular sizes. The results obtained show that (1) the Sp.EM/TM ratio
      of synthetic eumelanins increases as polymerization proceeds, (2) the Sp.EM/TM
      and PTCA/TM ratios in copolymers of DHI and DHICA correlate to the percentage
      content of DHICA-derived units, and (3) combination of the Sp.EM/TM and PTCA/TM
      ratios serves to estimate the DHICA content and the degree of polymerization in
      natural eumelanins.

PMID- 9177735
TI  - Tracing gluconeogenesis with deuterated water: measurement of low deuterium
      enrichments on carbons 6 and 2 of glucose.
AB  - The contribution of gluconeogenesis to glucose production in vivo can be measured
      by enriching body water with 0.5% 2H2O and measuring the glucose labeling ratio
      C6/C2 (Landau et al., J. Clin. Invest. 95, 172-178, 1995). We present further
      refinements of the measurements of the 2H enrichments on C6 and C2 of glucose.
      The transfer of 2H from C6 of glucose to hexamethylenetetramine (HMT) and
      extraction in preparation for gas chromatography-mass spectrometry can be done in
      a single test tube, without distillation of the intermediate formaldehyde. In
      addition, extraction of small amounts of HMT is greatly improved by making a HMT
      iodine adduct. For C2, glucose is reduced to sorbitol, and 2H on C2 is
      transferred enzymatically to [U-13C3]pyruvate, forming [U-13C3,2-2H]lactate. The
      latter is assayed by negative chemical ionization gas chromatography-mass
      spectrometry of the pentafluorobenzyl derivative. The natural enrichment of the
      [U-13C3]lactyl ion is only 0.4%, allowing measurements of 2H enrichment down to
      0.1%. These techniques were used in dogs infused with 2H2O and in isolated rat
      livers perfused with buffer containing 1 to 5% 2H2O. Our data reveal a difference
      in the rate of labeling of C6 and C2 of glucose in vivo. Lastly, in cows infused
      with [6,6-2H2]glucose, we show that the turnover of glucose can be economically
      measured by assaying low tracer enrichment (down to 0.1%) via
      hexamethylenetetramine.

PMID- 9177736
TI  - Optimal filter combinations for photographing SYPRO orange or SYPRO red dye
      stained gels.
AB  - Photography or electronic image acquisition is required to document results
      obtained from staining protein gels with the fluorescent SYPRO dyes. We found
      that, when using Polaroid type 667 or 57 instant films, the choice of optical
      filter combination and photographic exposure time strongly influences protein
      detection sensitivity limits. Ultraviolet light-blocking Kodak Wratten No. 2A and
      2B gelatin filters autofluorescence when illuminated at 300 nm. The use of these
      filters in combination with Wratten No. 22 or 25 filters or SYPRO gel
      photographic filters gives rise to increased background signals, which for long
      photographic exposures can obscure signals due to protein bands. Surprisingly,
      the use of these same ultraviolet lightblocking filters enhanced the protein
      detection sensitivity obtained with short photographic exposures. Under the
      conditions tested, we found minimal differences in performance for Polaroid type
      667 and 57 films.

PMID- 9177737
TI  - Factors influencing [3H]ryanodine binding to the skeletal muscle Ca2+ release
      channel.
AB  - Optimal [3H]ryanodine binding to skeletal muscle sarcoplasmic reticulum membranes
      is dependent on a number of factors such as Ca2+ concentration, ionic strength,
      and the presence of modulators of the Ca2+ release channel. The rate of
      association of [3H]-ryanodine with its binding site is slower than a diffusion
      limited process, and often the binding reaches a peak value which is followed by
      a slow decline. This phenomenon makes it extremely difficult to determine kinetic
      constants for [3H]ryanodine binding. The inclusion of bovine serum albumin (BSA)
      or the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
      (Chaps) in the incubation buffer prevents the decrease in [3H]ryanodine binding
      observed in association studies. BSA or Chaps slows this decline in binding
      partially by preventing a conversion to a more rapidly dissociating component.
      Pretreatment of the membranes with Chaps does not prevent the decrease in
      [3H]ryanodine binding, suggesting that Chaps is not exerting its effect by
      extracting a lipid or peripheral membrane protein. The decrease in affinity
      observed in the absence of BSA and Chaps appears to require the occupation of the
      high-affinity ryanodine binding site. Incubation for extended times in the
      absence of [3H]ryanodine prior to the initiation of the association produced
      similar curves to those obtained without preincubation. These combined results
      suggest that Chaps and BSA stabilize the ryanodine-modified Ca2+ release channel
      by preventing an alteration in the ryanodine binding site which leads to
      decreased affinity, thus allowing for a more quantitative interpretation of
      binding data.

PMID- 9177738
TI  - Albumin blue 580 fluorescence assay for albumin.

PMID- 9177739
TI  - A 96-well plate protein assay for samples containing sodium dodecyl sulfate and
      reducing agent using the multiscreen nitrocellulose filtration plate with amido
      black.

PMID- 9177740
TI  - Dampening of bait proteins in the two-hybrid system.

PMID- 9177741
TI  - A simplified procedure for a rapid and reliable assay of both glycogen and
      trehalose in whole yeast cells.

PMID- 9177742
TI  - Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes
      P450.

PMID- 9177743
TI  - Direct transfection of polymerase chain reaction-generated DNA fragments into
      mammalian cells employing ethidium bromide indicator and ultrafiltration.

PMID- 9177744
TI  - A fluorescamine assay for membrane protein and peptide samples with non-amino
      containing lipids.
AB  - A method is described for determining the concentration of membrane proteins and
      peptides in the presence of non-amino-containing lipids. The assay is
      quantitative when used for purified proteins and peptides of known sequence and
      qualitative when sequences are unknown or samples contain contaminating proteins.
      In this method, proteins and peptides are hydrolyzed to amino acids followed by
      derivatization by fluorescamine and spectroscopic detection in a mixed solvent
      system. A liquid-phase acid hydrolysis separates lipid from the sample and
      increases the sensitivity and accuracy of the assay. The aqueous-organic solvent,
      composed of 40% dimethylformamide, has two advantages. First, it suppresses
      differences in fluorescence between samples with and without residual hydrolyzed
      lipid, allowing direct comparison of samples and standards regardless of lipid
      content. Second, the solvent enhances the fluorescence of amino acid derivatives.
      While the fluorescence intensities of fluorescamine derivatives reach a maximum
      at approximately 40% dimethylformamide, the emission maximum wavelengths continue
      to blue-shift at higher concentrations of organic solvent. The selection of an
      acid hydrolysis mixture based on the fluorescence quenching by different acid
      mixtures is also reported.

PMID- 9177745
TI  - Immunofiltration purification for urinary leukotriene E4 quantitation.
AB  - Leukotriene E4 (LTE4) is a major leukotriene metabolite in urine. Urinary LTE4
      concentration is often utilized as an index of total leukotriene synthesis. A
      novel method employing immunofiltration for the purification of urinary LTE4 was
      developed. This immunofiltration method is based upon the addition of excess anti
      LTE4 antibody to urine which binds LTE4. Separation of bound LTE4 (high M(r))
      from high levels of unbound contaminants (low M(r)) is then accomplished by
      filtration through a 10,000 M(r) cut-off filter. The LTE4-antibody complex is
      separated by precipitation of the antibody with methanol which is subsequently
      removed by centrifugation. Following evaporation of the methanol, enzyme
      immunoassay is utilized for quantitation. This methodology was validated by
      determining the recovery of tritiated and unlabeled LTE4 added to urine and
      buffer and by comparison of results obtained with urine samples measured after
      HPLC purification (correlation r2 = 0.72). Reproducibility of the assay was
      assessed by analyzing the same sample on two different days (standard deviation
      of 18%). The mean urinary LTE4 levels in healthy subjects and asthmatics measured
      utilizing this method were found to be identical to levels determined by
      HPLC/immunoassay. The ease and accuracy of this assay make it amenable for the
      analysis of large numbers of samples.

PMID- 9177746
TI  - Screening panels of monoclonal antibodies using phage-displayed antigen.
AB  - A procedure is described to screen panels of hybridomas or purified monoclonal
      antibodies using antigen displayed on the surface of filamentous bacteriophage.
      In this system, samples containing murine monoclonal antibodies are incubated
      with phage-displayed antigen in microtiter plates coated with rabbit anti-mouse
      IgG, and bound antibody-phage complex is detected with horseradish peroxidase
      sheep anti-phage M13 conjugate. The assay has been validated with a panel of 16
      monoclonal antibodies directed against human plasminogen, using phage-displayed
      miniplasmin-(ogen) (amino acids Ala444 through Asn791 comprising kringle 5 and
      the proteinase domain of plasminogen) or microplasminogen (amino acids Ala543
      through Asn791 comprising the proteinase domain). Six monoclonal antibodies were
      identified directed against miniplasminogen and miniplasmin; this was confirmed
      using a microtiter plate coated with antigens. One of these monoclonal antibodies
      (MA-42B12) did not react with microplasminogen, suggesting that its epitope is
      comprised within the kringle 5 domain. This test is rapid and sensitive
      (detecting 10-20 ng/ml of monoclonal antibody), and screening can be performed
      using phage-displayed zymogens or active enzymes or selected domains thereof. The
      procedure eliminates the need for large amounts of purified antigen for
      screening. Furthermore, immunization can be performed with partially purified
      antigen because only antibodies raised against the antigen of interest will be
      identified with the use of phage-displayed antigen. Therefore, this test may
      offer distinct advantages over the classical one-site enzyme-linked immunosorbent
      assay using antigen-coated microtiter plates.

PMID- 9177747
TI  - Thiol-reactive, luminescent Europium chelates: luminescence probes for resonance
      energy transfer distance measurements in biomolecules.
AB  - Lanthanide chelates have recently been shown to be extremely promising
      luminescence probes for distance measurements in biomolecules using luminescence
      resonance energy transfer measurements [P. R. Selvin, T. M. Rana, and J. E.
      Hearst (1994) J. Am. Chem. Soc. 116, 6029-6030; P. R. Selvin, and J. E. Hearst
      (1994) Proc. Natl. Acad. Sci. USA 91, 10024-10028]. In this work we describe
      simple procedures for preparing highly fluorescent thiol-reactive europium
      chelates. These new compounds contain a uv-absorbing coumarin group which
      sensitizes europium emission, diethylenetriaminepentaacetic acid or
      triethylenetetraaminehexaacetic acid groups which provide europium chelating
      function, and a pyridyl disulfide group which allows specific modification of
      thiol groups. These reagents can be used to label proteins at Cys residues or
      synthetic oligonucleotides which contain thiol groups. Modification can be
      reversed easily by treatment with a reducing agent (dithiothreitol). Luminescence
      energy transfer between these new chelates and CY5 fluorochrome attached to the
      opposite ends of 15-bp double-stranded DNA was measured to test their usefulness
      for distance measurements in macromolecules. The distance measured between the
      chelate (donor) and CY5 (acceptor) was in the range expected for the length of 15
      bp DNA. The stability of europium chelates and their conjugates with a protein,
      the precision of distance measurements using these chelates, possible errors due
      to intramolecular energy transfer, and the modulation of the R0 value with
      deuterium oxide were tested. The results obtained fully confirmed the great
      potential of these new probes for sensitive, simple, and precise distance
      measurements in biomolecules using luminescence resonance energy transfer.

PMID- 9177748
TI  - Reactivation of C1-inhibitor polymers by denaturation and gel-filtration
      chromatography.
AB  - C1-inhibitor is a proteinase inhibitor in the serpin family. It is an important
      inhibitor of complement C1, plasma kallikrein, and factor XIIa, and as such is
      involved in regulating inflammatory pathways. Studies on the plasma-derived
      protein are hampered by the relative ease with which the protein converts to an
      inactive state on storage, under mild denaturing conditions, or by incubating in
      some unfavorable buffers. This inactivation is caused by formation of soluble
      polymers which can be visualized on native electrophoresis. In order to
      facilitate studies on both the plasma-derived protein and recombinant variants
      planned for the future, it was necessary to devise a method for the rapid
      reactivation of the polymers in high yield. It was found that nonionic detergents
      did not dissociate the polymers, but they were readily dissociated in 0.1% SDS.
      Treatment with 0.1% SDS followed by rapid removal of the SDS and refolding on an
      FPLC Superose 6 column allowed for recovery of about 15% of the protein in the
      active monomeric form. Eighty-five percent eluted as a range of higher order
      polymers. Using 8 M urea as the denaturant a 25% yield of active monomer was
      recovered. However, with 6 M guanidine hydrochloride as the denaturant, the yield
      of active monomer was almost 50%. The remaining material was not present as a
      range of polymeric species but was probably a dimer. Therefore this method is a
      useful technique to facilitate studies on C1-inhibitor. Moreover, the ability to
      produce monomer, dimer, and polymer forms of C1-inhibitor is useful for studies
      investigating the conformational changes which have occurred in the different
      forms.

PMID- 9177749
TI  - Water (H2O and D2O) molar absorptivity in the 1000-4000 cm-1 range and
      quantitative infrared spectroscopy of aqueous solutions.
AB  - Water (H2O and D2O) molar absorptivity was measured by Fourier transform infrared
      transmission spectroscopy in the 1000-4000 cm-1 range at 25 degrees C. A series
      of assembled cells with path lengths from 1.2 to 120.5 microns was used for these
      measurements. The optimal path length (the path length of aqueous solution at
      which the IR spectrum of solute, corrected for water absorbance, has the highest
      signal-to-noise ratio) was calculated for all water absorbance bands. The results
      presented here show that the optimal path length does not depend on solute
      properties and is inversely proportional to the solvent (water) molar
      absorptivity. The maximal signal-to-noise ratio for measurements of IR spectra of
      aqueous solution in the 1650 cm-1 spectral region, of primary interest in
      biological applications, can be obtained at an optimal cell path lengths of 3-4
      microns (H2O) and 40-60 microns (D2O). As an example, the signal-to-noise ratio
      was calculated as a function of the cell path length for the amide I (H2O) and
      amide I' (D2O) bands of an aqueous lysozyme solution. The molar absorptivities of
      water bands are several orders of magnitude weaker than those of the strongest
      bands of biological macromolecules in the same spectral regions. High net water
      absorbance in aqueous solutions is due simply to the very high molar
      concentration of water. A method is proposed for the quantitative measuring of
      the path length of the cell which exploits the molar absorptivity of the
      strongest water bands (stretching vibrations) or of bands which do not overlap
      with solute absorbance. A path length in the range from approximately 0.01 micron
      to approximately 1.0 mm can be determined with high precision using this
      technique for a samples of known concentration. Problems involved in the proper
      correction of strong water absorbance in IR spectra of aqueous solutions of
      biomolecules are discussed, including multiple reflections within the cell, the
      effects of pH, temperature, and perturbation of water spectral properties by
      polar solutes, as well as the selection of optimal spectral regions in which one
      may obtain the most precise absorbance corrections.

PMID- 9177750
TI  - A microtiter colorimetric assay for the HIV-1 protease.
AB  - We have developed a novel colorimetric assay for the HIV-1 protease that is
      suitable for high-throughput screening of inhibitors. This assay utilizes two
      nonenzymatic reaction steps, which are carried out in succession following
      enzymatic hydrolysis of a synthetic peptide. The first step involves a
      carbamylation reaction between cyanate and the nascent alpha amino group
      resulting from enzymatic hydrolysis. The second step involves a carbamidodiacetyl
      reaction between 2,3-butanedione monoxime (diacetylmonoxime) and the de novo
      carbamido compound. The entire assay can be performed in a microtiter plate and
      is amenable to automation. In addition, this peptidolysis assay is readily
      adaptable to other proteolytic enzymes and their substrates.

PMID- 9177751
TI  - Noninvasive, real-time method for the examination of thymidine uptake events-
      application of the method to V-79 cell synchrony studies.
AB  - [14C]Thymidine uptake into V-79 hamster lung fibroblasts has been successfully
      demonstrated using a noninvasive, real-time method utilizing Cytostar-T
      scintillating microplates. These plates are standard format, tissue culture
      treated, 96-well microplates with an integral scintillating base. The microplates
      permit the culture and observation of adherent cell monolayers. Biological
      activities of the cells can be studied by the provision of specific radiolabeled
      compounds. The biological activities of the adherent monolayer bring the specific
      radiolabel into proximity with the scintillating base and a scintillation signal
      is thereby generated. [14C]Thymidine incorporation on the microplates can be used
      to examine cell proliferation and cell cycle events. Using a combined mitotic
      shake-off/aphidicolin treatment to achieve synchronization, the thymidine
      incorporation activities of V-79 cells have been examined on Cytostar-T plates
      and correlated to traditional methods of determining incorporation. The method
      was further used to examine the effects of colcemid and olomoucine, both chemical
      inhibitors of cell proliferation, on synchronous populations of cells. The
      homogeneous detection format and the microplate nature of the method suggest a
      role for scintillating microplates in cell biology research and drug discovery.

PMID- 9177753
TI  - Amplified enzyme-linked-immunofilter assays enable detection of 50-10(5)
      bacterial cells within 1 hour.
AB  - Two enhanced enzyme-linked-immunofilter assay (ELIFA) methods for the rapid and
      quantitative detection of whole bacterial cells are described. In the first
      method, specific antibody bound to bacterial cells was amplified using a
      secondary antibody and detected by the conjugated enzyme activity (peroxidase) of
      a third antibody in a chemiluminescent assay. In the second method, a chromogenic
      substrate was used in conjunction with a biotinylated secondary antibody and
      avidin. Both assays were conducted within 55 min using a 96-well continuous flow
      immunofilter apparatus. The assay values were determined either as the
      reflectance of developed X-ray film placed over chemiluminescent membranes or of
      precipitated chromogen on the membrane surface. The biotin/avidin method enabled
      quantitative detection of approximately 60 to 10(5) cells. The detection limit
      (blank + 2 SD) of the chemiluminescent assay with a 30-s film exposure time was
      50 cells. The ELIFA methods described represent a considerable advance in
      sensitivity over previous immunological methods of detecting whole bacterial
      cells and suggest that immunological methods may approach PCR in sensitivity.

PMID- 9177752
TI  - A fluorescent microplate assay for diarrheic shellfish toxins.
AB  - A fluorescent enzyme inhibition assay for okadaic acid using 4-methylumbelliferyl
      phosphate and fluorescein diphosphate as substrates for the enzyme phosphatase 2A
      was developed. In the inhibition assay, performed in a microtiter plate, the PP2A
      was inhibited by adding okadaic acid and the resulting fluorescence enhancement
      derived from enzymatic hydrolysis of the substrate was quantified in a
      fluorescence plate reader. The measurable range of okadaic acid was 3.2 to 3200
      pg/ml with an IC50 = 0.1 nM. The detection limit of okadaic acid was 2.56 pg/well
      in buffer solutions and 12.8 ng/g hepatopancreas in shellfish extracts. The
      coefficient of variation (CV, n = 22) for each point ranged from 18.80 to 37.90%
      (mean 28.35%). The proposed method is very convenient, rapid, and sensitive by
      using the enzyme inhibition assay system and fluorescent reaction as a detection
      system. This work demonstrates that the fluorescent assay can be used to quantify
      the amount of okadaic acid in shellfish samples and also is valid for very dilute
      samples, such as phytoplankton samples.

PMID- 9177754
TI  - Real-time observation of affinity reactions using grating couplers: determination
      of the detection limit and calculation of kinetic rate constants.
AB  - The use of integrated optical grating couplers for the analysis of bioaffinity
      reactions in order to calculate kinetic rate constants was investigated. The
      specificity of the sensor surface was determined by adsorptive or covalent
      attachment of the specific ligands. As an evanescent field sensor, the specific
      interaction of the corresponding ligand could be observed in real time and
      without labels. The detection limit in terms of the molecular weight of the
      analyte was studied by the specific binding of biotinylated proteins of different
      molecular weights to avidin-loaded sensors. It was shown that grating coupler
      sensors allowed detection of compounds of at least 2000 daltons using high
      affinity receptors, while the direct sensing of low molecular analytes, such as
      biotin, could not be significantly achieved. Association rate constants were
      calculated for the interaction of the different biotinylated proteins to avidin
      covered sensors from single binding curves. Due to the strong binding between
      avidin and biotin, the dissociation of the formed complex could not be observed.
      Kinetic rate constants and equilibrium constants were determined by studying the
      interaction of human immunoglobulin with the immobilized receptor, protein G. For
      the four human immunoglobulin subclasses a high affinity to protein G was
      determined with affinity constants ranging from 3.3 to 8.4 x 10(8) M-1.

PMID- 9177756
TI  - Cloning and characterization of cDNAs from genes differentially expressed during
      the strawberry fruit ripening process by a MAST-PCR-SBDS method.
AB  - A vast number of clones carrying cDNAs from genes differentially expressed along
      the strawberry (Fragaria x ananassa c.v. Chandler) fruit ripening process has
      been isolated by screening of a subtractive cDNA library. The library was
      constructed and screened using a powerful procedure that combines the
      differential screening technique with a Southern blot screening by means of the
      polymerase chain reaction (PCR-SBDS procedure). Several clones have been
      partially sequenced and characterized and main similarities with other known
      genes from higher plants are presented. These comparisons reveal putative
      functions of these genes in the strawberry fruit ripening process.

PMID- 9177755
TI  - Isotope ratio mass spectrometry, compared with conventional mass spectrometry in
      kinetic studies at low and high enrichment levels: application to lipoprotein
      kinetics.
AB  - The aim of the present study was to compare the performances of gas
      chromatography/mass spectrometry (GC/MS) and gas
      chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) in stable
      isotope kinetic studies. In the analysis of cholesterol and leucine, GC/C/IRMS
      gave precise and linear results over a large scale of 13C enrichment (-22 to +760
      delta/1000 for cholesterol, -26 to +600 delta/1000 for leucine). Compared with
      GC/MS, GC/C/IRMS was much more accurate and reproducible, especially at low [13C]
      cholesterol enrichment (-12 delta/1000), with cholesterol samples ranging from
      0.11 to 17 ng. Cholesterol ester kinetics in rabbit plasma low-density
      lipoproteins was studied after injection of 3 mg [3,4-(13)C]cholesterol. A smooth
      and regular kinetic curve was obtained with GC/C/IRMS; results were much less
      reproducible with GC/MS. Finally, the performances of GC/C/IRMS were demonstrated
      in the simultaneous kinetic study of three human plasma apolipoproteins during a
      primed constant infusion of 0.7 mg.kg-1.h-1 L-[l-13C]leucine. Kinetic curves were
      obtained in very-low-density lipoproteins and low-density lipoproteins for
      apolipoprotein B100, and in high-density lipoproteins for apolipoproteins AI and
      AIL.

PMID- 9177757
TI  - Antibiotic resistance in Streptomyces lividans: fluorescence assay for
      streptogramin B lyase.
AB  - A fluorescence assay for streptogramin B lyase, an enzyme that confers resistance
      to streptogramin B antibiotics, has been developed. The antibiotic substrates are
      fluorescent and the linear peptide products formed in the lyase-catalyzed
      reaction are relatively nonfluorescent. The assay has potential for assessing
      bacterial resistance to streptogramin B antibiotics and will be utilized to
      direct the purification of streptogramin B lyase from bacterial extracts.

PMID- 9177758
TI  - Cell disruption of Escherichia coli by glass bead stirring for the recovery of
      recombinant proteins.

PMID- 9177759
TI  - Anisotropy values for liposomes from neonatal and adult erythrocytes differ after
      adjustment for optical density scattering.

PMID- 9177760
TI  - Polymerase chain reaction (PCR) detection and quantification using a short PCR
      product and a synthetic internal positive control.

PMID- 9177761
TI  - Basic fibroblast growth factor prolongs the proliferation of rat cortical
      progenitor cells in vitro without altering their cell cycle parameters.
AB  - Basic fibroblast growth factor (bFGF) has been shown to influence the survival,
      proliferation and differentiation of a variety of cell types in the nervous
      system. In this investigation we have examined the action of bFGF on: (i) the
      rate of proliferation; (ii) cell cycle parameters; (iii) the maintenance of cell
      division; (iv) the recruitment of quiescent cells; and (v) the degree of
      differentiation of cortical progenitor cells in cultures prepared from E16 rat
      embryos. The proliferation rate (labelling index) of cortical progenitor cells
      doubled in the presence of bFGF over 48 h. However, the lengths of the cell cycle
      phases were unchanged. Clones marked with a recombinant retrovirus on the first
      day in vitro (DIV) grew significantly larger in the presence of bFGF.
      Furthermore, many of the clones examined in control cultures had ceased to divide
      after a maximum of four cell cycles, whereas almost all clonally related cells
      were still dividing in the presence of bFGF 4 days later, i.e. for at least six
      cell cycles. Basic FGF also stimulated the division of quiescent progenitor
      cells, which otherwise would have differentiated or undergone cell death. The
      degree of neuronal and glial differentiation was studied after 5 DIV using MAP-2
      and GFAP immunocytochemistry. In the presence of bFGF, the percentage of MAP-2
      labelled cells was less than half that of control cultures, whereas the number of
      cells immunoreactive for nestin (a marker of progenitor cells) remained very
      high. Cells immunoreactive for GFAP were present in bFGF-treated cultures, yet
      were extremely rare in control conditions. These experiments show that bFGF, a
      potent mitogen for cortical progenitor cells, has no effects on the parameters of
      their cell cycle but extends their proliferative capability, promotes their
      survival and delays their differentiation into neurons.

PMID- 9177762
TI  - The development of auditory callosal connections in normal and hypothyroid rats.
AB  - Previous studies have shown that hypothyroidism modifies the development of
      callosal connections. In particular, adult hypothyroid rats have fewer callosally
      projecting neurons in layers II-III of the auditory cortex and more in layer V.
      This might be due to disturbance in the stabilization/elimination of juvenile
      callosal axons, or to abnormal neuronal migration during cortical histogenesis.
      To distinguish between these possibilities we have studied the distribution of
      callosally projecting auditory neurons at different postnatal ages using
      retrogradely transported tracers, and the cortical neurogenetic gradients using
      DNA labelling with 5-bromo-2'-deoxiuridine. In hypothyroid rats, injected at
      postnatal day 5 (P5) and killed at P18-20, most of the neurons retrogradely
      labelled from the contralateral hemisphere are distributed between layers IV and
      VI, as in older rats. In hypothyroid rats, many neurons are at locations
      inappropriate for their birthdate, including the subcortical white matter,
      resulting in more diffuse radial neurogenetic gradients. These results indicate
      that early induced hypothyroidism alters neuronal migration and prevents the
      establishment of callosal connections from cortical layers II-III.

PMID- 9177763
TI  - Categorical perception of somesthetic stimuli: psychophysical measurements
      correlated with neuronal events in primate medial premotor cortex.
AB  - In this paper we describe a type of neuron of the medial premotor cortex (MPC)
      that discharged differentially during a categorization task and reflected in
      their activity whether the speed of a tactile stimulus was low or high. The
      activity of these neurons was recorded in the MPC contralateral (right MPC, n =
      88) and ipsilateral (left MPC, n = 103) to the stimulated hand of four monkeys
      performing this somesthetic task. Animals performed the task by pressing with the
      right hand one of two target switches to indicate whether the speed of probe
      movement across the skin of the left hand was low or high. Differential responses
      of MPC neurons occurred during the stimulus and reaction time period. We used an
      analysis based on signal detection theory to determine whether these differential
      responses were associated with the animal's decision. According to this analysis,
      104 of the 191 neurons (right MPC, n = 48; left MPC, n = 56) coded the
      categorization of the stimulus speeds (categorical neurons). In a light
      instruction task, we tested the possibility that the categorical neurons (n = 71)
      were associated with the intention to press, or with the trajectory of the hand
      to one of the two target switches used to indicate categorization. In this
      situation, each trial began as in the somesthetic categorization task, but one of
      the two target switches was illuminated beginning with the skin indentation,
      continued during the delay period and turned off when the probe was lifted off
      from the skin. This condition instructed the animal which target switch was
      required to be pressed for reward. Very few neurons (14 of 71) maintained their
      differential responses observed in the categorization task. Some categorical
      neurons (n = 5) were also studied; the animal categorized the tactile stimulus
      speeds, but knew in advance whether the stimulus speed was low or high
      (categorization + light instruction). This was made by illuminating one of the
      two target switches which was associated with the stimulus speed. The categorical
      response was considerably attenuated in this condition. Interestingly, during the
      delay period, these neurons reflected in their activity whether the stimulus was
      low or high. A number of the categorical MPC neurons (n = 30) were studied when
      the same set of stimuli, used in the categorization, were delivered passively.
      None of these neurons responded in this condition. These results suggest that the
      MPC, apart from its well-known role in motor behavior, is also involved in the
      animal's decision during the execution of this learned somesthetic task.

PMID- 9177764
TI  - Analysis of optic flow in the monkey parietal area 7a.
AB  - Environmentally relevant stimuli were used to examine the selectivity of area 7a
      neurons to optic flow using moving, flickering dots. Monkeys performed a
      psychophysical task requiring them to detect changes in translation, rotational
      and radially structured optic flow fields consisting of collections of moving
      dots which are free of form cues. The neurons in area 7a were selectively
      responsive to all the different types of moving stimuli. Two types of tuning for
      motion selectivity were found. Some neurons were tuned to distinguish a
      particular direction of optic flow (e.g. radial expansion versus radial
      compression), while others were tuned to distinguish between different classes of
      optic flow (e.g. radial motion versus planar rotation). The latter tuning was
      unlike that reported for area MST by others and may represent a novel
      representation of optic flow. The response of these neurons to translating bars
      was compared to that of optic flow fields. There appeared to be no similarity in
      the tuning to the two types of motion. Furthermore, there does not appear to be
      an identity between the neurons that could be classified as opponent vector and
      those selective for radial optic flow. Area 7a is involved in the further
      analysis of optic flow beyond the cortical areas MT and MST and provides a novel
      representation of motion. These results are consistent with the neurons in area
      7a utilizing motion for the construction of a spatial representation of extra
      personal space.

PMID- 9177765
TI  - Three distinct families of GABAergic neurons in rat visual cortex.
AB  - In the cortex inhibition is mediated predominantly by GABAergic interneurons.
      Although all of these neurons use the same neurotransmitter, studies in the rat
      frontal cortex have shown that they are molecularly and physiologically diverse.
      It is not known whether similar subgroups of GABAergic neurons exist in primary
      visual cortex and how these different inhibitory neurons are inserted into
      specific cortical circuits. We have used immunostaining with antibodies against
      gamma aminobutyric acid (GABA), parvalbumin (PV), calretinin (CR), somatostatin
      (SOM), calbindin (CB) and nitric oxide synthase (NOS) to probe for colocalization
      of known markers of GABAergic interneurons. The results show that the majority of
      PV (100%), SOM (89.8%) and CR (93.9%) staining neurons are GABA positive. PV
      immunoreactive neurons constitute a distinct group that show no overlap with CR,
      SOM and NOS expressing cells and only a minor overlap (5.3%) with CB. PV
      immunoreactive cells account for 50.8% of GABAergic neurons. A second group of
      SOM expressing neurons accounts for 16.9% of GABAergic cells. None of these cells
      colocalize PV or CR, but 1.7% of SOM neurons stain for NOS and 86.3% show CB
      immunoreactivity. The third distinct group of CR expressing cells accounts for
      17.0% of GABAergic neurons. All of these are PV, CB, SOM and NOS negative. CB
      expressing neurons represent a heterogeneous group that includes GABAergic and
      non-GABAergic cells. Our findings indicate that GABAergic neurons in rat area 17
      are organized in at least three separate families that can be identified by the
      expression of PV, CR and SOM. These cells account for 84.9% of GABAergic neurons.
      These results extend previous observations in rat frontal agranular cortex and
      suggest that in visual cortex the inhibitory network is composed of similar cell
      types.

PMID- 9177766
TI  - Dual role of substance P/GABA axons in cortical neurotransmission: synaptic
      triads on pyramidal cell spines and basket-like innervation of layer II-III
      calbindin interneurons in primate prefrontal cortex.
AB  - In spite of accumulating evidence on the potent neuromodulatory, neuroprotective,
      trophic and memory-enhancing effects of the neuropeptide substance P (SP) in the
      cerebral cortex, the excitatory or inhibitory nature of the cortical SP
      innervation remains unclear and the postsynaptic targets of SP fibers are not
      defined. To obtain further insight into these issues, we have examined SP
      containing axons and their postsynaptic targets in the prefrontal cortex of adult
      monkeys with single- and double label immunocytochemistry combined with light and
      correlated electron microscopy. SP fibers in the primate prefrontal cortex,
      unlike those in the rat cortex, preferentially innervate cortical layers I, II
      and upper layer III. Our results demonstrate for the first time that all SP
      immunoreactive boutons in all cortical layers contain GABA. Of the entire sample
      of SP boutons, 53% synapse on dendritic shafts, 39% on dendritic spines and 8% on
      cell bodies. Another new finding is that synapse-forming SP boutons, in addition
      to their known innervation of pyramidal cells, form pericellular baskets around
      interneurons in layers II and upper III, a subpopulation of which contains
      calbindin D28k. Finally, the study also revealed that SP boutons frequently
      participate in 'synaptic triads' with spines which receive another (asymmetric,
      putatively excitatory amino acid-utilizing) synapse. Our findings indicate that
      SP/GABA axons in the primate prefrontal cortex modulate excitatory amino acid
      mediated neurotransmission and control feed-forward disinhibitory GABAergic
      circuits in supragranular cortical layers.

PMID- 9177767
TI  - High-resolution EEG mapping of cortical activation related to working memory:
      effects of task difficulty, type of processing, and practice.
AB  - Changes in cortical activity during working memory tasks were examined with
      electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened
      with magnetic resonance imaging (MRI)-based finite element deblurring. Eight
      subjects performed tasks requiring comparison of each stimulus to a preceding one
      on verbal or spatial attributes. A frontal midline theta rhythm increased in
      magnitude with increased memory load. Dipole models localized this signal to the
      region of the anterior cingulate cortex. A slow (low-frequency), parietocentral,
      alpha signal decreased with increased working memory load. These signals were
      insensitive to the type of stimulus attribute being processed. A faster (higher
      frequency), occipitoparietal, alpha signal was relatively attenuated in the
      spatial version of the task, especially over the posterior right hemisphere.
      Theta and alpha signals increased, and overt performance improved, after practice
      on the tasks. Increases in theta with both increased task difficulty and with
      practice suggests that focusing attention required more effort after an extended
      test session. Decreased alpha in the difficult tasks indicates that this signal
      is inversely related to the amount of cortical resources allocated to task
      performance. Practice-related increases in alpha suggest that fewer cortical
      resources are required after skill development. These results serve: (i) to
      dissociate the effects of task difficulty and practice; (ii) to differentiate the
      involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize
      frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the
      feasibility of using anatomical MRIs to remove the blurring effect of the skull
      and scalp from the ongoing EEG. The results are discussed with respect to those
      obtained in a prior study of transient evoked potentials during working memory.

PMID- 9177768
TI  - Organization of intrinsic connections in owl monkey area MT.
AB  - Area MT (middle temporal) is a well-defined visual representation common to all
      primates, which shows a clear selectivity to the analysis of visual motion. In
      the present study we examined the architecture of the intrinsic connections in
      area MT in an attempt to reveal its organizing principles and its potential
      relationship to the functional domains in area MT. Intrinsic connections were
      studied by placing small injections of the tracer biocytin in area MT of seven
      adult owl monkeys (Aotus nancymae). The injections were targeted at well-defined
      orientation domains revealed using optical imaging of intrinsic signals. The
      distribution of axons labeled by these injections was related both to the
      cytochrome oxidase histochemistry and to the layout of functional domains in area
      MT and surrounding tissue. Tracer injections in the superficial layers of area MT
      produced a complex network of extrinsic and intrinsic axonal connections. Clear
      instances of extrinsic connections were observed between area MT proper and the
      MT crescent situated postero-medially to it. The intrinsic connections were
      laterally spread and organized in patch-like clusters with an average distance
      from injection center to the furthest patch of 1.8 +/- 0.55 mm (+/-SD, n = 9).
      The overall axonal distribution tended to be anisotropic, i.e. the patches were
      distributed within an elongated ellipse [average anisotropy ratio: 1.86 +/- 0.66
      (+/-SD)] and were asymmetrically distributed about either side of the injection
      site [average asymmetry ratio: 2.3 +/- 0.7 (+/-SD)]. Finally, there was a
      tendency for the intrinsic connections to connect to functional domains of
      similar orientation preference in area MT. However, this tendency varied
      substantially between individual cases. The highly specific nature of MT lateral
      connections puts clear constraints on models of surround influences in the
      receptive fields of MT neurons.

PMID- 9177769
TI  - Molecular characterization of a genetically unstable region containing the SMS
      critical area and a breakpoint cluster for human PNETs.
AB  - Recently we demonstrated the clustering of deletion breakpoints in the
      pericentromeric region of human chromosome 17p in human primitive neuroectodermal
      tumors (PNETs). Chromosomal disruption was shown to occur between the two markers
      D17S805 and D17S953, a region previously shown to be deleted in the Smith-Magenis
      syndrome. To characterize the molecular basis of this genomic instability, we
      established clone contigs covering this region. An initial physical map of
      chromosome 17p has been constructed with overlapping sets of YACs. YAC clones
      were transformed into five clone contigs according to their content of 30
      previously known and 16 newly established sequence-tagged sites (STSs). To
      circumvent the complications inherent in YAC technologies, such as internal
      deletions, chimerism, and complex rearrangements, we then converted the YAC
      contigs to PAC and cosmid contigs. Thirty-nine individual PAC/cosmid clones were
      identified and were used to construct six different PAC/cosmid contigs ranging
      from 130 to 1200 kb in size and covering approximately 2.5 Mb of genomic DNA. The
      composite YAC/PAC/cosmid map covers a region of > 6 Mb of genomic DNA consisting
      of four different clone contigs of up to 2.9 Mb in size. We have demonstrated
      that three STSs (D17S58, PS1, and D17S842) are duplicated, suggesting the
      occurrence of low abundant repetitive sequences in this region. By integration of
      publicly available information we further mapped 10 genes and ESTs to their
      precise chromosomal positions and thus could exclude or identify them as
      candidate genes for PNET and/or the Smith-Magenis syndrome.

PMID- 9177770
TI  - IL-2-induced proliferative response is controlled by loci Cinda1 and Cinda2 on
      mouse chromosomes 11 and 12: a distinct control of the response induced by
      different IL-2 concentrations.
AB  - Lymphocytes of mouse strains BALB/cHeA (BALB/c) and STS/A (STS) differ in the IL
      2-induced proliferative response, STS being a high and BALB/c a low responder in
      the range of concentrations 125-2000 IE/ml. We analyzed the genetic basis of this
      strain difference using the recombinant congenic (RC) strains of the BALB/c-c
      STS/Dem (CcS/Dem) series. This series comprises 20 homozygous strains all derived
      from two parental inbred strains: the "background" strain BALB/c and the "donor"
      strain STS. Each CcS/Dem strain contains a different, random set of approximately
      12.5% genes of the donor strain STS and approximately 87.5% genes of the
      background strain BALB/c. In this way, the STS genes controlling the IL-2-induced
      response became separated into individual CcS/Dem strains, as indicated by
      differences in the magnitude of the IL-2-induced response among CcS/Dem strains
      (M. Lipoldova et al., 1995, Immunogenetics 41: 301-311). To map some of these
      genes, we tested F2 hybrids between one of the high-responder RC strains, CcS-4,
      and the low-responder parental strain BALB/c. We found that the response to high
      IL-2 concentrations is controlled by a locus, Cinda1 (cytokine-induced activation
      1), on chromosome 11 near the marker D11Mit4. The response to a lower dose of IL
      2 tested on lymphocytes of the same mice was found to be controlled by another
      locus, Cinda2, in the centromeric part of chromosome 12, the higher response
      being linked to the STS allele of the marker D12Mit37. Understanding the action
      of genetic factors, such as Cinda1 and Cinda2, that control T cell function is
      expected to contribute to the efficient analysis of the genetic control of
      susceptibility to infections and autoimmune diseases.

PMID- 9177771
TI  - A 2-Mb YAC contig and physical map of the natural killer gene complex on mouse
      chromosome 6.
AB  - We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that
      contains the natural killer gene complex (NKC). The map comprises a contig of 14
      overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers.
      NKC genetically linked genes encode > 17 proteins that directly control innate NK
      cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes
      are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes
      are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals
      of mouse chromosome 6 and human chromosome 12p that include the NKC are
      conserved. NKC species conservation suggests that the human NKC may contain
      orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high
      resolution NKC map will facilitate investigation of NKC gene regulation and
      identification of phenotypically defined gene products that confer NK cell
      defense against viral pathogens.

PMID- 9177772
TI  - Human TNF receptor-associated factor 5 (TRAF5): cDNA cloning, expression and
      assignment of the TRAF5 gene to chromosome 1q32.
AB  - Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are signal
      transducers for members of the TNF receptor superfamily. We previously identified
      murine TRAF5 (mTRAF5) and showed that it specifically interacts with the
      lymphotoxin-beta receptor (LT-beta R) and activates the transcription factor NF
      kappa B. Here we have cloned the human TRAF5 homologue (hTRAF5) by cross
      hybridization with mTRAF5 cDNA. hTRAF5 cDNA is composed of 2894 nucleotides with
      a 557-amino-acid open reading frame that exhibits 77.5 and 80% identity to mTRAF5
      at the nucleotide and amino acid levels, respectively. Northern blot analysis
      revealed that hTRAF5 mRNA is expressed in all visceral organs. Western blotting
      revealed that hTRAF5 protein was abundantly expressed in the human follicular
      dentritic cell line, FDC-1, and to a much lesser degree in several tumor cell
      lines. Interspecific backcross mapping revealed that Traf5 is located in the
      distal region of mouse chromosome 1, which shares a region of homology with human
      chromosome 1q. Fluorescence in situ hybridization confirmed regional localization
      to human chromosome 1q32.

PMID- 9177773
TI  - Genomic localization of the human gene for KCNA10, a cGMP-activated K channel.
AB  - Potassium (K) channels are important components of virtually all cells, and they
      play critical roles in many cellular functions. KCNA10 represents a new class of
      K channel specifically regulated by cGMP and postulated to mediate the effects of
      substances that increase intracellular cGMP. Since KCNA10 has the potential to be
      useful in candidate gene analysis of inherited diseases, the human gene for
      KCNA10 was characterized. Fluorescence in situ hybridization indicates that human
      KCNA10 maps to chromosome 1 at p13.1-->p22.1. Finer mapping of the gene was
      achieved by PCR of a set of CEPH YAC clones that spanned the region of interest.
      We found that YAC 818b9 contains human KCNA10. These data indicate human KCNA10
      maps to 1p13.1 and resides within the genetic interval defined by microsatellite
      loci D1S2809 and D1S2726. That region of chromosome 1 contains another K channel
      gene, KCNA3.

PMID- 9177774
TI  - Elucidation of the sequence and the genomic organization of the human dentin
      matrix acidic phosphoprotein 1 (DMP1) gene: exclusion of the locus from a
      causative role in the pathogenesis of dentinogenesis imperfecta type II.
AB  - The dentin matrix acidic phosphoprotein 1 (DMP1) gene has been mapped to human
      chromosome 4q21 and shown to exhibit no recombination with the autosomal dominant
      disorder of dentin formation, dentinogenesis imperfecta type II. In the current
      study, sequencing of DMP1 cDNA and genomic clones has indicated that the human
      gene contains an open reading frame of 1539 bp, which predicts a highly acidic,
      serine-rich protein of 513 amino acids. Comparison of the human DMP1-coding
      sequence with that of the rat, mouse, and cow indicated that the predicted
      protein contains a conserved hydrophobic signal peptide sequence and an Arg-Gly
      Asp cell attachment sequence. The gene is encoded by six exons, the splicing
      phase of which is type 0, the first exon containing solely 5' untranslated
      sequence. Sequencing of each of the coding exons in individuals affected by
      dentinogenesis imperfecta type II failed to reveal any disease-specific
      mutations, suggesting that mutations in DMP1 are not causative of this condition
      at least in the two families examined in this study.

PMID- 9177775
TI  - Genomic structure, evolution, and expression of human FLII, a gelsolin and
      leucine-rich-repeat family member: overlap with LLGL.
AB  - The Drosophila melanogaster flightless-I gene is involved in cellularization
      processes in early embryogenesis and in the structural organization of indirect
      flight muscle. The encoded protein contains a gelsolin-like actin binding domain
      and an N-terminal leucine-rich repeat protein-protein interaction domain. The
      homologous human FLII gene encodes a 1269-residue protein with 58% amino acid
      sequence identity and is deleted in Smith-Magenis syndrome. We have cloned the
      FLII gene and determined its nucleotide sequence (14.1 kb). FLII has 29 introns,
      compared with 13 in Caenorhabditis elegans and 3 in D. melanogaster. The
      positions of several introns are conserved in FLII-related genes and in the
      domains and subdomains of the gelsolin-like regions giving indications of
      gelsolin gene family evolution. In keeping with its function in indirect flight
      muscle in Drosophila, the human FLII gene was most highly expressed in muscle.
      The FLII gene lies adjacent to LLGL, the human homologue of the D. melanogaster
      tumor suppressor gene lethal(2) giant larvae. The 3' end of the FLII transcript
      overlaps the 3' end of the LLGL transcript, and the corresponding mouse genes
      Fliih and Llglh also overlap. The overlap region contains poly(A) signals for
      both genes and is strongly conserved between human and mouse.

PMID- 9177776
TI  - Nucleotide sequence analysis of the HLA class I region spanning the 237-kb
      segment around the HLA-B and -C genes.
AB  - To elucidate the detailed gene organization of the human leukocyte antigen (HLA)
      class I region on chromosome 6, seven contiguous cosmid genomic clones covering
      the 237-kb segment around the HLA-B and -C loci were subjected to DNA sequencing
      by the shotgun strategy to give a single contig of 236,822 bp from the MICA gene
      (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C. This region was
      confirmed to contain four known genes, MICA, HLA-17, HLA-B, and HLA-C, from
      centromere to telomere. Further, a new member of the P5 multicopy genes was found
      to be about 1.3 kb upstream of the HLA-17 gene and designated P5.8. Five novel
      genes designated NOB1-5 were identified by RT-PCR and Northern blot
      hybridization. In addition, two pseudogenes, dihydrofolate reductase pseudogene
      (DHFRP) and ribosomal protein L3 homologous gene (RPL3-Hom), were also found in
      the vicinity of the HLA-B and -C genes, respectively. The two segments (about 40
      kb) downstream of the HLA-B and HLA-C genes showed high sequence homology to each
      other, suggesting that segmental genome duplication including the major
      histocompatibility complex (MHC) class I gene must have occurred during the
      evolution of the MHC.

PMID- 9177777
TI  - Identification of a novel human kinesin-related gene (HK2) by the cDNA
      differential display technique.
AB  - We have used the cDNA differential display technique to isolate genes regulated
      by the synthetic retinoid N-(4-hydroxyphenyl)-all-trans-retinamide (HPR), a
      cancer chemopreventive agent in vivo and a powerful inducer of apoptotic cell
      death in vitro. Here we report the identification of a novel gene, the expression
      of which is markedly up-regulated in tumor cells after treatment for 30-60 min
      with HPR. The full-length cDNA of this gene, determined by screening of a human
      placenta cDNA, is 3.5 kb long and contains an open reading frame of 2037 nt. The
      gene is > 90% homologous to the mouse KIF2, a gene belonging to the family of
      kinesin-related motor proteins, and we therefore named it HK2 (human kinesin 2).
      A shorter form of the HK2 mRNA (HK2s), containing a 57-nt deletion in the open
      reading frame, has also been detected. Northern analysis revealed that HK2 is
      widely expressed among hemopoietic and nonhemopoietic cell lines and tissues. By
      the use of radiation hybrids, HK2 has been localized to chromosome 5q12-q13.
      Kinesins constitute a superfamily of motor proteins that use energy liberated
      from ATP hydrolysis to move cargo along microtubules and are implicated in
      mechanisms of mitosis or meiosis. The role of HK2 in the growth-inhibitory and
      apoptotic responses elicited by HPR remains to be established.

PMID- 9177778
TI  - Physical and linkage mapping of human chromosome 17 loci to dog chromosomes 9 and
      5.
AB  - Genome mapping in the dog is in its early stages. Here we illustrate an approach
      to combined physical and linkage mapping of type 1 anchor (gene) loci in the dog
      using information on syntenic homology from human and mouse, an interbreed
      cross/backcross, and a strategy for isolation of dog genomic clones containing
      both gene-specific sequences and simple sequence repeat polymorphisms. Eleven
      gene loci from human chromosome 17q (HSA17q) were mapped to the centromeric two
      thirds of dog chromosome 9 (CFA9), an acrocentric chromosome of medium size:
      P4HB, GALK1, TK1, GH1, MYL4, BRCA1, RARA, THRA1, MPO, NF1, and CRYBA1. Eight of
      these were also positioned on a linkage map spanning 38.6 cM. Based on combined
      fluorescence in situ hybridization and linkage mapping, the gene order on CFA9 is
      similar to that of the homologous genes on HSA17q and mouse chromosome 11
      (MMU11), but in the dog the gene order is inverted with respect to the
      centromere. Canine loci, GALK1, TK1, GH1, MYL4, THRA1, and RARA constitute a
      closely linked group near the centromeric end of CFA9, spanning a genetic
      distance of only 4.7 cM. Canine NF1 and CRYBA1 lie distally, near the lower
      border of the Giemsa band adjacent to the distal one-third of CFA9. NF1 and
      CRYBA1 are loosely linked to the more centromeric group (31.2 cM). No HSA17 genes
      were found on the telomeric one-third of CFA9. Painting of dog chromosomes with a
      human whole chromosome 17 probe showed hybridization with only the proximal two
      thirds of CFA9, consistent with the conclusion that the distal one-third
      corresponds to a segment or segments of other human chromosomes. Two loci, GLUT4
      and PMP22, located on HSA17p, were mapped by FISH to dog chromosome 5 in a region
      also identified by the whole human chromosome 17 paint, indicating disruption of
      HSA17 syntenic homology at the centromere.

PMID- 9177779
TI  - Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate
      region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.
AB  - In this paper we describe the assembly and restriction map of a 1.05-Mb cosmid
      contig spanning the candidate region for familial Mediterranean fever (FMF), a
      recessively inherited disorder of inflammation localized to 16p13.3. Using a
      combination of cosmid walking and screening for P1, PAC, BAC, and YAC clones, we
      have generated a contig of genomic clones spanning approximately 1050 kb that
      contains the FMF critical region. The map consists of 179 cosmid, 15 P1, 10 PAC,
      3 BAC, and 17 YAC clones, anchored by 27 STS markers. Eight additional STSs have
      been developed from the approximately 700 kb immediately centromeric to this
      genomic region. Five of the 35 STSs are microsatellites that have not been
      previously reported. NotI and EcoRI mapping of the overlapping cosmids,
      hybridization of restriction fragments from cosmids to one another, and STS
      analyses have been used to validate the assembly of the contig. Our contig
      totally subsumes the 250-kb interval recently reported, by founder haplotype
      analysis, to contain the FMF gene. Thus, our high-resolution clone map provides
      an ideal resource for transcriptional mapping toward the eventual identification
      of this disease gene.

PMID- 9177780
TI  - Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human
      CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3.
AB  - In the interest of cloning and analyzing the genes responsible for two very
      different diseases, the Rubinstein-Taybi syndrome (RTS) and acute myeloid
      leukemia (AML) associated with the somatic translocation t(8;16)(p11;p13.3), we
      constructed a high-resolution restriction map of contiguous cosmids (contig)
      covering 1.2 Mb of chromosome 16p13.3. By fluorescence in situ hybridization and
      Southern blot analysis, we assigned all tested RTS and t(8;16) translocation
      breakpoints to a 100-kb region. We have previously reported exact physical
      locations of these 16p breakpoints, which all disrupt one gene we mapped to this
      interval: the CREB-binding protein (CBP or CREBBP) gene. Intriguingly, mutations
      in the CBP gene are responsible for RTS as well as the t(8;16)-associated AML.
      CBP functions as an integrator in the assembly of various multiprotein regulatory
      complexes and is thus necessary for transcription in a broad range of
      transduction pathways. We report here the cloning, physical mapping,
      characterization, and full cDNA nucleotide sequence of the human CBP gene.

PMID- 9177781
TI  - Plectin transcript diversity: identification and tissue distribution of variants
      with distinct first coding exons and rodless isoforms.
AB  - Plectin is a widely expressed protein that is very large in size and that has all
      the attributes of a multifunctional crosslinking and organizing element of the
      cytoskeleton. It displays a multidomain structure, versatile binding activities,
      and subcellular localizations that enable it to strengthen cells against
      mechanical stress forces. Moreover, hereditary gene defects in plectin cause
      epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with
      muscular dystrophy. Here we report the analysis of the exonintron organization of
      the rat plectin gene and the identification of several different isoforms on the
      transcriptional level. We show that of 35 coding exons identified, 4 serve as
      alternative first exons splicing into the same successive exon 2, which is the
      first of 7 exons encoding a highly conserved actin-binding domain. RNase
      protection mapping of transcripts containing 3 of the identified 4 alternate
      first exons revealed their coexpression in rat glioma C6 cells and in a series of
      different rat tissues that we examined. Significant variations in expression
      levels of first exons indicated the possibility of tissue-specific promoter
      usage. In addition, plectin splice variants lacking exon 31 (> 3 kb), which
      encodes the entire rod domain of the molecule, were identified in a variety of
      rat tissues. This study provides first insights into a complex plectin gene
      regulatory machinery with similarities to that of dystrophin.

PMID- 9177782
TI  - An integrated transcript map of human chromosome 1p35-p36.
AB  - The distal short arm of human chromosome 1 (1p) is rearranged in a variety of
      malignancies, and several genetic diseases also map to this region. We have
      constructed an integrated transcript map to precisely define the positions of
      genes and expressed sequence tags (ESTs) previously mapped to 1p35-p36, a region
      spanning approximately 40 Mb. To anchor the integrated map, a framework genetic
      map was constructed with 24 genetic markers and a marker order of 1000:1 odds,
      yielding an average resolution of 2.8 cM. An additional 106 genetic markers were
      localized relative to the framework genetic map. To place markers more precisely
      within 1p35-p36, a chromosome 1-specific, radiation-reduced hybrid (RH) panel was
      created. Individual DNA fragments of the RH panel were identified and ordered by
      PCR with the framework genetic map. A total of 250 markers, including 142 genes
      and ESTs, were mapped by PCR against the RH panel. The map has an observed
      resolution of 800 kb, and the results closely match and more precisely define
      previous mapping information for most markers. This map will help to identify
      candidate genes for genetic diseases mapping to distal 1p and is fully integrated
      with existing genetic and RH maps of the human genome.

PMID- 9177783
TI  - Npm3: a novel, widely expressed gene encoding a protein related to the molecular
      chaperones nucleoplasmin and nucleophosmin.
AB  - We report the cloning and initial characterization of the cDNAs, gene, and
      pseudogene of Npm3, a novel murine gene that encodes a protein related to the
      nuclear chaperone phosphoproteins, nucleoplasmin and nucleophosmin. Npm3 is
      located approximately 5 kb upstream of Fgf8 on mouse Chromosome 19 and consists
      of six exons spanning 2 kb. The first five exons code for an acidic protein of
      19.0 kDa that contains a potential nuclear localization signal and potential
      phosphorylation sites for several kinases. Npm3 was expressed in all mouse
      tissues examined. On the basis of the similarity of Npm3 to nucleoplasmin and
      nucleophosmin in amino acid sequence, protein features, and exon structure, we
      propose that Npm3 is a new member of, and may share basic functions with, the
      nucleoplasmin/ nucleophosmin family of molecular chaperone proteins.

PMID- 9177784
TI  - Chromosome mapping and expression of the human interleukin-13 receptor.
AB  - Interleukin-13 (IL-13) is a cytokine secreted by activated T cells and shares
      most but not all biological activities with interleukin-4 (IL-4). Both cytokines
      play an important role as a switch factor directing synthesis of IgE; they act on
      monocytes and endothelial cells, but unlike IL-4, IL-13 does not act on T cells.
      These cytokines have both common and distinct components in their respective
      receptors. Based on sequence similarity shared by cytokine receptor family
      members, we have identified a cDNA encoding the human IL-13 receptor (IL-13R).
      This cDNA was used to examine the pattern of IL-13R mRNA expression by Northern
      blot analyses of poly(A)+ RNA purified from different human tissues and cell
      lines. Among several myeloma cell lines analyzed, the U266 cell line was the only
      one found to express IL-13R transcripts. This cell line is also the only one
      described as producing IgE. The IL-13R gene was mapped to chromosome Xq24 by in
      situ hybridization. Interestingly, this locus is near that of the CD40 ligand
      gene, the product of which is also involved, like IL-13, in proliferation and IgE
      isotype switching of human B cells. The human IL-13R gene maps between two
      cytokine receptor genes located on the chromosome arm Xq region: the interleukin
      2 receptor gamma chain gene (Xq13.1) and the interleukin-9 receptor gene (Xq28).
      The lack of nucleotide sequence similarity suggests unrelated evolutionary
      pathways between these receptor genes.

PMID- 9177785
TI  - Structure of the human gene (COX6A2) for the heart/muscle isoform of cytochrome c
      oxidase subunit VIa and its chromosomal location in humans, mice, and cattle.
AB  - We have mapped the gene for the heart/muscle isoform of cytochrome c oxidase
      (COX) subunit VIa in three mammalian species and isolated the human COX6AH gene
      (HGMW-approved symbol COX6A2). The bovine gene was mapped by somatic cell hybrid
      mapping panels to bovine chromosome BTA 25 with 94-95% concordance. The mouse
      gene (Cox6ah) was mapped using an interspecific backcross panel from the cross
      (C57BL/6J x Mus spretus)F1 x Mus spretus probed with the mouse COX VIa-H cDNA.
      Cox6ah was located on distal chromosome 7, between D7Mit8 and D7Mit13. From the
      regions of known gene conservation among these three species, we predicted that
      human COX6AH would be located on chromosome 16p. We hybridized a human x rodent
      mapping panel of somatic cell hybrids with the human cDNA to confirm this
      assignment. These data taken together indicated that the human COX6AH gene is
      located on the short arm of chromosome 16 and facilitated the isolation of the
      human gene from a chromosome 16-enriched library. The human COX6AH gene spans
      about 1 kb and contains three exons and two small introns. The sequences of the
      proximal 5' flanking regions of COX6AH genes are highly conserved between human,
      bovine, and rodent.

PMID- 9177786
TI  - The molecular basis of the obese mutation in ob2J mice.
AB  - The recessive ob2J mutation in mice results in an obese phenotype that is
      identical to that of the original ob allele. Initial studies indicated that ob2J
      mice fail to synthesize ob RNA in adipose tissue. Here we report the genomic
      organization of the mouse obese gene and establish the molecular genetic basis of
      the ob2J mutation. The ob2J mutation is the result of the insertion of a
      retroviral-like tranposon in the first intron of the ob gene. The insertion is a
      member of the ETn family of transposons and contains several splice acceptor and
      polyadenylation sites. This leads to the production of chimeric RNAs in which the
      ob first exon is spliced to sequences in the ETn insertion. As a consequence
      mature ob RNA is not synthesized, and leptin, the encoded protein, is not
      produced.

PMID- 9177787
TI  - Structure of the human ARHG locus encoding the Rho/Rac-like RhoG GTPase.
AB  - Members of the Rho/Rac/Cdc42Hs family of GTPases have been shown to participate
      in many aspects of the signaling of cell growth and differentiation. Although the
      biochemical properties of these GTPases have been extensively studied, very
      little is known about their gene structure and regulation. RhoG, a member related
      to Rac and Cdc42Hs, is activated at the transcriptional level in the mid-G1 phase
      of stimulated fibroblasts. As a first step toward the characterization of the
      regulatory elements involved in serum-regulated expression, we isolated and
      determined the structure of the corresponding human locus (ARHG, localized in
      11p15.4-p15.5). This is the first gene structure of a member of the
      Rho/Rac/Cdc42Hs family. At variance with Ras and Rab3A genes, ARHG contains a
      single intron larger than 20 kb that splits a 62-nt-long 5' noncoding first exon
      from the rest of the mRNA. The sequences upstream of the cap sites exhibit
      transcriptional activity. They are G/C-rich and devoid of TATA or CAAT boxes, as
      found for many housekeeping genes, including Ras genes.

PMID- 9177788
TI  - Genomic structure and expression of the human heme A:farnesyltransferase (COX10)
      gene.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with a 1.5-Mb tandem
      DNA duplication in chromosome 17p11.2-p12, while hereditary neuropathy with
      liability to pressure palsies (HNPP) is associated with a 1.5-Mb deletion at this
      locus. The 1.5-Mb CMT1A monomer unit duplicated in CMT1A and deleted in HNPP is
      flanked by two 24-kb direct repeats termed the CMT1A-REPs. Recently, sequence
      analysis of the CMT1A-REPs revealed that they contain an internal exon of the
      COX10 gene. To characterize COX10, encoding human heme A:farnesyltransferase, the
      genomic region was isolated and the gene structure and expression profile were
      determined. COX10 spans approximately 135 kb and consists of seven exons. Exons I
      V are telomeric to the 1.5-Mb CMT1A monomer unit, whereas exon VII is located
      within this 1.5-Mb region. Exon VI is contained within the distal CMT1A-REP. All
      splice sites conform to the GT/AG rule. Analysis of the putative promoter region
      of the COX10 gene indicates that it lacks conventional TATA and CAAT boxes, but
      it does have several potential transcription factor-binding sites. This gene is
      expressed in multiple tissues with highest expression observed in the heart,
      skeletal muscle, and testis.

PMID- 9177789
TI  - Human synaptotagmin V (SYT5): sequence, genomic structure, and chromosomal
      location.
AB  - We have determined the sequence, genomic structure, and chromosomal location of
      the human synaptotagmin V (SYTV) gene. The human SYTV gene encodes a 386-amino
      acid product which is 91% identical to rat Syt V. The human SYTV open reading
      frame is interrupted by seven introns which can be alternatively spliced. Human
      SYTV was found to lie very close to SYTIII on chromosome 19q13.4 by PCR analysis
      of somatic cell hybrid DNA and by DNA hybridization to arrayed cosmids of the
      chromosome 19 metric physical map. This provides the first report of linked
      synaptotagmin genes.

PMID- 9177790
TI  - Exon-intron structure of a 2.7-kb transcript of the STM7 gene with
      phosphatidylinositol-4-phosphate 5-kinase activity.
AB  - The STM7 gene encodes a novel phosphatidylinositol-4-phosphate 5-kinase (PtdInsP
      5-kinase) that is subject to alternative splicing and developmental control. We
      have recently presented data indicating that several splice variants of STM7
      incorporate elements of the X25 sequence, previously implicated in the
      pathogenesis of Friedreich's ataxia by the detection of an intronic GAA repeat
      expansion as the predominant mutation in affected individuals. We now report the
      exon-intron structure of STM7.I and primer sequences designed to facilitate full
      characterization, including details relating to a novel exon (STM7; exon 17)
      derived from the 3'-UTR of the PRKACG gene. The detection of a mutation(s) within
      these exons would provide additional support for the hypothesis that a defect in
      phosphoinositide metabolism gives rise to the disease phenotype.

PMID- 9177791
TI  - Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2.
AB  - We previously described the cDNA sequence of HPC-1/syntaxin 1A (HGMW-approved
      symbol STX1A) from rat and bovine brains. HPC-1/syntaxin 1A belongs to the
      syntaxin family and is apparently involved in intracellular membrane transport
      and the exocytosis of neurotransmitters. In this study, we isolated the cDNA and
      the genomic DNA clone for human HPC-1/syntaxin 1A and carried out gene mapping.
      Polymerase chain reaction analysis of human/rodent somatic cell hybrid panels and
      fluorescence in situ hybridization analysis using a genomic DNA clone provided
      evidence that the gene for human HPC-1/syntaxin 1A maps to chromosome region
      7q11.2.

PMID- 9177792
TI  - Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome
      11p15.5-p15.4.
AB  - We have recently reported the identification and cloning of the gene encoding
      p59ILK, a novel protein ser/thr kinase that is found in physiologic complexes
      with beta integrin subunits. ILK is a potential protoonocogene that appears to
      function in mediating signal transduction by beta 1 family integrins.
      Fluorescence in situ hybridization analysis of metaphase and decondensed free
      chromatin fibers localized ILK to 11p15.5-p15.4. This position was also confirmed
      by relational mapping using well-characterized translocations with breakpoints in
      chromosome band 11p15. Our results indicate that ILK maps between HBBC and CALC
      loci, in the 11p15.5-p15.4 band interval. This location may be important in
      evaluating the potential role of p59ILK in tumorigenesis since it has been shown
      that this region is associated with both genomic imprinting and loss of
      heterozygosity in certain types of tumor.

PMID- 9177793
TI  - Human acyl-coenzyme A synthetase 3 cDNA and localization of its gene (ACS3) to
      chromosome band 2q34-q35.

PMID- 9177794
TI  - Assignment of the human serine/threonine protein phosphatase 4 gene (PPP4C) to
      chromosome 16p11-p12 by fluorescence in situ hybridization.

PMID- 9177795
TI  - A general approach to error estimation and optimized experiment design, applied
      to multislice imaging of T1 in human brain at 4.1 T.
AB  - In this report, a procedure to optimize inversion-recovery times, in order to
      minimize the uncertainty in the measured T1 from 2-point multislice images of the
      human brain at 4.1 T, is discussed. The 2-point, 40-slice measurement employed
      inversion-recovery delays chosen based on the minimization of noise-based
      uncertainties. For comparison of the measured T1 values and uncertainties, 10
      point, 3-slice measurements were also acquired. The measured T1 values using the
      2-point method were 814, 1361, and 3386 ms for white matter, gray matter, and
      cerebral spinal fluid, respectively, in agreement with the respective T1 values
      of 817, 1329, and 3320 ms obtained using the 10-point measurement. The 2-point,
      40-slice method was used to determine the T1 in the cortical gray matter,
      cerebellar gray matter, caudate nucleus, cerebral peduncle, globus pallidus,
      colliculus, lenticular nucleus, base of the pons, substantia nigra, thalamus,
      white matter, corpus callosum, and internal capsule.

PMID- 9177796
TI  - Longitudinal relaxation and diffusion measurements using magnetic resonance
      signals from laser-hyperpolarized 129Xe nuclei.
AB  - Methods for T1 relaxation and diffusion measurements based on magnetic resonance
      signals from laser-hyperpolarized 129Xe nuclei are introduced. The methods
      involve optimum use of the perishable hyperpolarized magnetization of 129Xe. The
      necessary theoretical framework for the methods is developed, and then the
      methods are applied to measure the longitudinal relaxation constant, T1, and the
      self-diffusion constant, D, of hyperpolarized 129Xe. In a cell containing natural
      abundance 129Xe at 790 Torr, the T1 value was determined to be 155 +/- 5 min at
      20 degrees C and at 2.0 T field. For a second cell at 896 Torr, at the same field
      and temperature, the T1 value was determined to be 66 +/- 2 min. At a higher
      field of 7.05 T, the T1 values for the two cells were found to be 185 +/- 10 and
      88 +/- 5 min, respectively. The 129Xe self-diffusion constant for the first cell
      was measured to be 0.057 cm2/ s and for the second cell it was 0.044 cm2/s. The
      methods were applied to 129Xe in the gas phase, in vitro; however, they are, in
      principle, applicable for in vivo or ex vivo studies. The potential role of these
      methods in the development of newly emerging hyper-polarized 129Xe MRI
      applications is discussed.

PMID- 9177797
TI  - NMR of laser-polarized 129Xe in blood foam.
AB  - Laser-polarized 129Xe dissolved in a foam preparation of fresh human blood was
      investigated. The NMR signal of 129Xe dissolved in blood was enhanced by creating
      a foam in which the dissolved 129Xe exchanged with a large reservoir of gaseous
      laser-polarized 129Xe. The dissolved 129Xe T1 in this system was found to be
      significantly shorter in oxygenated blood than in deoxygenated blood. The T1 of
      129Xe dissolved in oxygenated blood foam was found to be approximately 21 (+/-5)
      s, and in deoxygenated blood foam to be greater than 40 s. To understand the
      oxygenation trend, T1 measurements were also made on plasma and hemoglobin foam
      preparations. The measurement technique using a foam gas-liquid exchange
      interface may also be useful for studying foam coarsening and other liquid
      physical properties.

PMID- 9177798
TI  - Vascularized pedicle bone-grafting for nontraumatic avascular necrosis of the
      femoral head. A 5- to 11-year follow-up.
AB  - We investigated the results of 31 hips in 26 patients with nontraumatic (n = 20)
      and steroid-induced (n = 6) avascular necrosis of the femoral head (ANFH) treated
      with vascularized iliac pedicle bone graft (PBG). The average age at operation
      was 38.3 years. Three were women and 23 men. The average follow-up was 8.0 years.
      The Harris hip score prior to operation and at latest follow-up improved from 62
      to 83; one hip collapsed and was revised with a bipolar endoprosthesis. At the
      final follow-up, 19 hips (63%) were clinically rated as good to excellent, 4
      fair, and 7 poor. At the final follow-up, 15 of 27 hips (56%) of stage II before
      operation showed progressive collapse after bone grafting. In steroid-induced
      ANFH, in three women, 2 of 4 hips showed poor results. These results are only
      slightly better than those of core decompression and no better than those
      obtained after decompression and simple nonvascularized grafts to provide support
      for the subchondral bone. We concluded that vascularized PBG is sometimes
      indicated for ANFH in an early stage before collapse of the femoral head.

PMID- 9177799
TI  - Pathological and hemodynamic study in a new model of femoral head necrosis
      following traumatic dislocation.
AB  - The blood of the femoral head is thought to be supplied by vessels originating
      from the medial and lateral circumflex femoral arteries and via the marrow cavity
      of the neck. Therefore, it is difficult to induce osteonecrosis of the femoral
      head when the marrow cavity of the neck is preserved. In the present study, we
      established a new model of femoral head necrosis by dislocating the hip joint and
      ligating the medial and lateral circumflex femoral arteries and veins.
      Measurement of femoral head blood flow revealed that a marked decrease to 14.7%
      of the control value was achieved by both hip dislocation and ligation of blood
      vessels. Pathologic examination showed no necrosis with either dislocation or
      ligation alone, whereas at 2 and 4 weeks 80% of the animals subjected to both
      procedures showed widespread necrosis. These pathologic findings considered in
      the light of results of the blood flow measurements suggest that a decrease in
      femoral head blood flow below 20% of the control value is needed to cause
      osteonecrosis. In addition, magnetic resonance images (MRI) of the model were
      evaluated in the combined dislocation and ligation group at 4 weeks (n = 5).
      Changes on MRI were seen in 3 of 5 dogs. The necrotic changes of the femoral head
      are thought to be detectable on MRI within 4 weeks after ischemia without
      enhancement.

PMID- 9177800
TI  - Results of humeral stump angulation osteotomy.
AB  - Between 1972 and 1989 angulation osteotomy was performed on 61 patients with long
      humeral stumps at the Orthopaedic Hospital of Heidelberg University. Marquardt's
      surgical technique was used to improve function in patients who had undergone
      above-elbow amputation and in children with a risk of terminal osseous
      overgrowth. Thirty-one patients with 43 angulation osteotomies were followed up.
      Of the 10 adults followed up, the osteotomy had not straightened, whereas with
      the 33 angulation osteotomies in children, one had straightened out within 6
      months, seven within 12 months and a further 12 up to 24 months after surgery.
      The only recognizable reason for this difference was the patient's age depending
      on whether humeral growth was not yet completed. Marquardt's angulation
      osteotomy, however, is still the only surgical technique that improves humeral
      stump function, providing a rotation-stable humeral prosthesis and a free-moving
      shoulder joint.

PMID- 9177801
TI  - Mechanical testing of the tension band wire fixation in the proximal femur.
AB  - The mechanical stability of proximal femoral osteotomies fixed by the tension
      band wire technique was studied in flexion-compression and torsion tests. The
      fixation consisted in crossing the section with two Kirschner wires and with a
      wire cerclage applied to the tension surface. The study was conducted in three
      steps. First, cyclinders of wood were cut either transversely or at 30 degrees of
      inclination in relation to the long axis of the specimen, and fixed with two
      Kirschner wires and a wire cerclage. We concluded that the inclination of the
      plane of section significantly increased the stability of fixation. No
      significant difference was observed when oblique sections were made in the
      reverse orientation. Second, 30 degrees subtrochanteric varus osteotomies were
      performed in dog femurs, so that the section plane was transverse in one group
      and oblique in another, after closing the osteotomy. In both groups the fixation
      was achieved by two Kirschner wires that crossed the osteotomy and a wire
      cerclage placed on the lateral cortex (tension surface). We concluded that
      inclination of the osteotomy plane increased the stability of osteosynthesis in
      bone specimens, as already seen with the wood pieces. Third, the stability of
      tension band wire fixation was compared with that provided by the AO/ASIF
      paediatric angled plate. Varus osteotomies (30 degrees) were created at the
      subtrochanteric level of paired dog femurs. On one side, the femur was fixed with
      Kirschner wires and a wire cerclage as described previously. For the other femur,
      the osteotomy was fixed with the angled plate. We found that both types of
      fixation presented the same stability in flexion-compression tests. However,
      under torsion the tension band wire fixation was 30%-50% less stable than the
      plate fixation.

PMID- 9177802
TI  - Biomechanical analysis of the effects of single high-dose vitamin D3 on fracture
      healing in a healthy rabbit model.
AB  - In a previous ultrastructural study, the benefit of a single high dose of vitamin
      D3 on fracture healing in a healthy animal model was demonstrated. This study
      examined the biomechanical consequences of applying a single high dose of vitamin
      D3 in a healthy rabbit model subsequent to femoral fracture. The fracture load,
      the values of energy absorbed until fracture and the flexural rigidity values of
      the vitamin D group were significantly higher than the corresponding ones of the
      control group in the case of fracture. On the other hand, for intact bones, those
      values did not differ significantly between the two groups. It was concluded that
      single high-dose vitamin D3 application had positive effects on fracture healing
      in a healthy animal model, as far as the parameters related to mechanical
      strength are concerned.

PMID- 9177803
TI  - Tibial avulsion fracture of the posterior cruciate ligament: K-wire or screw
      fixation? A retrospective study of 26 patients.
AB  - Although the posterior cruciate ligament (PCL) is not frequently injured, a
      greater understanding of its role in stabilizing the knee joint, mechanism of
      injury and treatment has developed. Isolated avulsion injuries constitute only a
      subgroup of PCL injuries, but nevertheless several operative techniques have been
      described for the fixation of the avulsed bony fragment. In order to investigate
      whether K-wire or screw fixation yields better long-term results, we examined 26
      patients at an average of 10.5 years after the initial operation. Clinical
      examination, activity level, radiographic evaluation and instrumented
      measurements did not reveal any significant differences. All the patients had an
      excellent functional result. Thus, both K-wire and screw fixation are recommended
      for bony PCL avulsion injuries.

PMID- 9177804
TI  - Use of preoperative vascular embolisation in spinal metastasis resection.
AB  - Preoperative selective embolisation was carried out on 17 patients with spinal
      metastases from various primary tumours. There was a significant reduction in the
      blood loss (2088 ml) and infusion volume requirement (3500 ml) and more
      favourable postoperative haemoglobin (Hb) development compared with the non
      embolised but otherwise identical control group. The reduced intraoperative
      bleeding manifested itself in the form of greater clarity and a less complicated
      intraoperative course. Particularly with a dorsal approach, the reduced bleeding
      permitted more exact preparation and more extensive tumour resection.
      Preoperative embolisation is thus a valuable aid in spinal metastasis resection.
      Given suitable indications and exact positioning of the embolising material, no
      significant complications should arise. The method as a whole calls for close
      collaboration between interventional radiologists and spinal orthopaedists.

PMID- 9177805
TI  - Instrumented measurement of anterior-posterior translation in knees with chronic
      anterior cruciate ligament tear.
AB  - Anteroposterior translation of the knee joint was measured with a Knee Signature
      System device on 12 women and 14 men with a unilateral, chronic, isolated,
      anterior cruciate ligament (ACL) tear. A control group with stable knees
      consisted of 10 women and 10 men. Anterior translation at 178 N load of the
      uninjured knees was 8.0 mm (+/-2.2 mm) and in knees with an ACL tear, 14.2 mm (+/
      4.2 mm). Corresponding values for anteroposterior translation were 12.1 mm (+/
      2.5 mm) and 19.3 mm (+/-4.9 mm), respectively. A difference of 3 mm or more in
      anteroposterior translation at 178 N load between injured and uninjured knees
      indicated an ACL tear with 85% specificity and 88% sensitivity.

PMID- 9177806
TI  - High stability of the Ilizarov ringfixator in a metacarpal fracture of an Arabian
      foal.
AB  - In a case of I degree open multifragmentary metacarpal fracture of a 4-week-old
      Arabian foal, an osteosynthesis with the Ilizarov ringfixator was performed.
      Immediate full weight-bearing (100 kg) was possible, demonstrating the high
      stability of the Ilizarov ringsystem. After 12 weeks, sufficient bony union was
      achieved, and the fixator could be removed. At that time, the body weight of the
      foal was 170 kg. In our opinion, this case proves the high stability and
      efficiency of the ringsystem under difficult and unusual conditions.

PMID- 9177807
TI  - Stabilization of an inserted tricalcium phosphate spacer enhances the healing of
      a segmental tibial defect in sheep.
AB  - The effect of inserting a tricalcium phosphate (TCP) spacer stabilized by a rigid
      or non-rigid fixation technique on the healing of segmental tibial defects of
      critical size was established. The osteotomized tibiae, 11 with and 8 without TCP
      spacers, were fixed by an external circular device in 11 mature sheep and by
      plates in 8 mature sheep, respectively. Healing was evaluated
      roentgenographically 16 weeks after the operation. Compared with the defects
      without TCP spacers, enhanced stability and healing were observed in the defects
      with TCP spacers under an identical external fixation. Furthermore, a
      significantly higher incidence of healing was obtained with plate fixation than
      with external device fixation in the TCP-implanted defects (P < 0.04). An
      abundant bridging callus was roentgenograpically demonstrated in most of the
      healed defects, but none in the unhealed defects. The TCP spacer with its
      mechanical integrity enhances the stability of external fixation, and the stable
      immobilization provided by rigid fixation is essential for osteoconduction of an
      inserted TCP spacer in the healing of segmental diaphyseal defects in sheep.

PMID- 9177808
TI  - Multiple chop wounds in Hong Kong. An epidemiological study of an unusual injury.
AB  - Knife injuries can be classified into stabbing injuries and multiple laceration
      or multiple chops, the latter being much more common in Chinese communities. It
      is the mark of criminal gang attacks with their tendency to use long knives and
      choppers rather than guns. The intention is often to wound rather than kill. A
      survey of 89 cases revealed that 90% of the victims are men, with a mean age of
      27 years; 75% was admitted to the hospital at night, and in 78% of the cases the
      assailants were persons unknown, or so we were told by the victims. The reasons
      for the attacks were also not given. Most of the women victims were assaulted by
      their spouse. Some 74% of the patients suffered three to six lacerations; 62% of
      the injuries were on the extensor surfaces of the upper limbs, while the hand and
      the back of the trunk were also common sites. The type of management differs from
      that for stabbing injuries. There were no fatalities, and less than half of the
      patients required blood transfusion. The average hospital stay was 6.2 days. The
      morbidity of these injuries involves damaged tendons and nerves.

PMID- 9177809
TI  - Experimental study of the hydrodynamic effects of irrigation suction drainage.
AB  - The function of irrigation suction drainage, as an additional method in the
      treatment of bone infection, is associated with hydrodynamic problems that can
      only be experimentally examined. The visualization of liquid movement in the
      experimental model was realized by adding a colored ink to the input drain of the
      drainage system. When only 2000 ml of liquid was used daily (80 drops/min), the
      ink penetrated the experimental cavity only through the most proximal holes in
      the input drain. It spread slowly and irregularly through the liquid in the
      experimental bottle, forming pocket deposits and leaving sediment. When 6000 ml
      of liquid was applied daily (240 drops/min), ink quickly penetrated the cavity
      through all holes in the drain, leading to turbulence and dispersing equally in
      the bottle. Decoloration of the model bottle was faster because the output
      drainage was more efficient. With an increased flow, i.e., with more liquid used
      in the drainage, a better result was achieved. This was manifested in a swift
      decoloration and rinsing of the cavity.

PMID- 9177810
TI  - Rupture of flexor tendons due to pisotriquetral osteoarthritis.
AB  - We are reporting a case of a flexor profundus tendon rupture of the little finger
      due to pisotriquetral osteoarthrosis. Resection of the pisiform bone and
      resurfacing of the carpal tunnel with the joint capsule was performed for the
      osteoarthrosis and free tendon grafting for the tendon rupture. The tendon
      grafting and a subsequent tenolysis restored the function of the little finger.
      Other than radiological changes in the pisotriquetral joint, the diagnostic value
      of preoperative radiocarpal arthrography was emphasized in this rare complication
      of pisotriquetral arthrosis.

PMID- 9177811
TI  - Chondrosarcoma secondary to synovial chondromatosis. Report of two cases and a
      review of the literature.
AB  - Malignant transformation of synovial chondromatosis into chondrosarcoma is
      unusual. Thirteen cases and one series have been reported; only four of them
      developed in the hip. The overall survival is about 50%, possibly because of the
      difficulty of arriving at a correct early diagnosis (radiographically and
      histologically) and subsequent adequate surgical therapy. We report two patients
      (ages 30 and 50 years) in whom synovial chondrosarcoma developed in previously
      excised synovial chondromatosis of the hip. The diagnosis was made with modern
      imaging techniques (computed tomography and magnetic resonance imaging) and
      verified by open biopsy. The early recognition allowed a wide limb-saving
      resection; both patients are disease free 3 and 2 years after surgery.

PMID- 9177812
TI  - Fracture of ossified Achilles tendon.
AB  - Ruptures of Achilles tendon are quite common. We here report a case of fracture
      in an ossified mass of Achilles tendon in an 84-year-old male patient. The mass
      occurred 78 years following surgery for bilateral equinus deformities of his
      ankle. Clinically, he had a palpably definite gap in the ossified area of the
      Achilles tendon, which was confirmed by a roentgenogram and a magnetic resonance
      scan of his left ankle. He was treated conservatively in a plaster cast for 12
      weeks. The overall functional result a year after his treatment was quite
      satisfactory.

PMID- 9177813
TI  - Reasoning requirements for diagnosis of heart disease.
AB  - Over the past dozen years, the Heart Disease Program (HDP) has been developed to
      assist physicians in reasoning about cardiovascular disorders. Driven by several
      evaluations, the inference mechanism has progressed from a logic based model, to
      a Bayesian Probability Network (BPN) and finally a pseudo-Bayesian network with
      temporal and severity reasoning. Though aspects of cardiovascular reasoning are
      handled well by BPNs, temporal reasoning, homeostatic feedback mechanisms and
      effects of disease severities require additional inference strategies. This
      article discusses how these reasoning problems are handled, and deals with
      closely linked issues in building the user interface to collect detailed
      cardiovascular data and provide clear explanations of diagnoses.

PMID- 9177814
TI  - Diagnosing congenital heart defects using the Fallot computational model.
AB  - This paper describes a computational model developed for the diagnosis of
      multiple defects. If multiple defects interact, meaning that the cues observable
      for multiple defects are not a sum of the cues observable for the component
      defects, diagnosis is particularly difficult. We developed a description and
      classification of the ways cues change when defects interact. A computational
      model (named Fallot) was implemented and a knowledge-base was constructed for the
      diagnosis of congenital heart defects. On each case, Fallot performs recognition
      based reasoning followed by solution construction and evaluation with the cue
      combination methods. Fallot was tested on cases from hospital files and correctly
      diagnoses cases with multiple interacting defects for which conventional methods
      are not applicable or fail.

PMID- 9177815
TI  - Spatio-temporal reasoning for multi-scale modeling in cardiology.
AB  - In this paper, we present an overview of the CARDIOLAB environment where the
      heart's electrical activity is modeled at distinct space and time scales.
      CARDIOLAB uses three models, two of which are based on cellular automata, and the
      third on qualitative simulation. They are combined around a blackboard for multi
      scale quantitative and qualitative modeling of cardiac electrical activity. A
      general account on how spatio-temporal representation and reasoning methods are
      applied to produce heuristic associations is also presented.

PMID- 9177816
TI  - DIAVAL, a Bayesian expert system for echocardiography.
AB  - DIAVAL is an expert system for the diagnosis of heart diseases, including several
      kinds of data, mainly from echocardiography. The first part of this paper is
      devoted to the causal probabilistic model which constitutes the knowledge base of
      the expert system in the form of a Bayesian network, emphasizing the importance
      of the OR gate. The second part deals with the process of diagnosis, which
      consists of computing the a posteriori probabilities, selecting the most probable
      and most relevant diagnoses, and generating a written report. It also describes
      the results of the evaluation of the program.

PMID- 9177817
TI  - An expert system for diagnosis of acute myocardial infarction with ECG analysis.
AB  - Coronary heart disease is one of the most prevalent and costly health care
      problems in the world. The early and accurate diagnosis of coronary heart disease
      is a major problem in emergency settings. However, many primary and secondary
      hospitals and primary emergency units lack cardiologists on call which makes the
      diagnosis difficult. This paper describes an expert system for diagnosis of acute
      myocardial infarction developed to aid physicians without cardiology
      specialization. Our main goal was to develop an expert system that assists in the
      diagnosis and indicates the need of hospitalization in a coronary unit.

PMID- 9177818
TI  - Allergic reactions to phenytoin in a general hospital in Singapore.
AB  - Phenytoin is used for the treatment and prevention of fits. We investigated all
      patients reported to have phenytoin allergy in our hospital and found 42
      confirmed cases. Sixty-nine percent were female and 83.3% were Chinese. The mean
      age of the patients was 46.5 years. The reactions reported were maculopapular
      rash (71.4%), Stevens-Johnson syndrome (14.3%), fever (4.8%), generalized
      exfoliative dermatitis (2.4%), toxic epidermal necrolysis (2.4%), vasculitis
      (2.4%) and agranulocytosis (2.4%). In conclusion, the majority of reported
      allergic reactions to phenytoin were cutaneous (92.9%) and one fifth of these
      were potentially life-threatening.

PMID- 9177819
TI  - Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing
      antigen presentation with concomitant decrease of HLA-DQ antigen on macrophages.
AB  - Allergen activates T lymphocytes responsive to interleukin 2 (IL-2) in allergic
      patients but not in normal individuals. This response was suppressed by anti
      allergic agent, Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo [4, 5]
      cyclohepta [1, 2-b] thiophen-10 (9H)-one hydrogen (fumarate). Prolonged culture
      of antigen-presenting adherent cells impaired the ability to present
      Dermatophagoides farinae (Df) antigen to T cells, whereas stimulation of adherent
      cells with recombinant interferon-gamma (IFN-gamma) restored the antigen
      presenting capability. The maintained antigen presenting ability of adherent
      cells treated with IFN-gamma was also suppressed by Ketotifen. Fluorescence
      activated cell sorter (FACS) analysis disclosed that Ketotifen selectively
      reduced the expression of HLA-DQ antigen, crucial restriction elements in Df
      antigen-related responses, on macrophages but not on B cells, even in the
      presence of IFN-gamma. Collectively, Ketotifen prevented macrophages from
      inducing allergen-activated T lymphocytes' responsiveness to IL-2 at least in
      part by decreasing the expression of HLA-DQ antigen.

PMID- 9177820
TI  - The abnormalities of nailfold capillaries in scleroderma as assessed by video
      image analysis and photomicroscopy.
AB  - Scleroderma is a systemic connective tissue disease in which the diagnosis in
      supported by morphological changes in nailfold capillary size and density. These
      changes are open to observer bias. In this paper we describe 2 objective methods
      that allow quantitative definition of capillary changes, video image analysis
      (VIA) and photomicroscopy. VIA was used to assess 15 healthy control subjects and
      22 patients with scleroderma. Scleroderma patients had a significantly larger
      capillary diameter (43 microns versus 20 microns, p = 0.0001) and capillary
      density was reduced by a mean factor of 0.5. Image stored on computer will
      facilitate serial assessments of nailfold capillary changes and possibly provide
      information on disease progression.

PMID- 9177821
TI  - Comparison between dual and tri-colour reagents for the analysis of lymphocyte
      subsets.
AB  - The aim of this project was to compare dual and tri-colour reagents for
      lymphocyte immunophenotyping. A total of 37 patient and normal specimens were
      immunophenotyped concurrently with the following mean values (% dual vs tri
      colour): CD3 (69.4 vs 68.3) CD4 (24.0 vs 24.2) and CD19 (13.9 vs 12.6). A
      comparison of the results obtained using the paired t test showed that there were
      no significant differences for cells expressing CD3, CD4 and CD19. However, there
      was a significant difference in the NK (18.3 vs 16.3) cell component. A major
      advantage in using 3 colour immunophenotyping is the ability to analyse specimens
      that cannot be analysed using dual colour reagents due to debris or contamination
      of the gate with non-lymphocytic cells.

PMID- 9177822
TI  - A study of cell-mediated immune response to pancreatic antigens in patients with
      fibrocalculous pancreatic diabetes.
AB  - In order to investigate whether there was any association between autoimmunity to
      pancreatic antigens with FCPD as well as IDDM, cell-mediated immune response to
      pancreatic antigens was studied by lymphoproliferation assay in 7 FCPD, 17 IDDM,
      33 NIDDM patients and 102 normal controls. Optimal pancreatic antigen
      concentrations used were 100, 150 and 200 micrograms/ml. Positive results were
      considered for each concentration of antigens tested, at stimulation index (SI) >
      (mean +/- 2 SD) SI obtained from normal age-matched controls with the use of the
      corresponding concentration of antigen. The one who gave positive result with any
      of these optimal antigen concentrations was considered to be the responder to
      pancreatic antigens. With this criterion, the responders were found to be 3/7
      (42.9%) FCPD, 6/17 (35.3%) IDDM and 6/33 (18.2%) NIDDM patients; while there were
      11 of all 102 (10.8%) normal controls.

PMID- 9177823
TI  - Production of mouse anti-CD4 antibodies by DNA-based immunization.
AB  - The intramuscular injection of plasmid DNA encoding an antigenic protein has been
      developed recently as a tool for immunization. DNA-based immunization was shown
      to generate immune responses against the encoded antigen in diverse animal
      species. In this report, we present the use of DNA-based immunization for the
      production of antibodies to CD4, a human leukocyte surface molecule. Mice were
      injected intramuscularly with eukaryotic expression vector containing cDNA
      encoding CD4 protein, termed CD4-DNA, and were subsequently assayed for anti-CD4
      antibody production by indirect immunofluorescence. Sera collected from 2 of 3
      inoculated mice reacted with CD4 expressing transfected COS cells and Sup-T1
      cells. Anti-CD4 antibody activity was abolished by adsorption with CD4 molecule
      expressing cells. CD4+ cell depleted lymphocytes were also used to confirm the
      specificity of the anti CD4 antibodies present in immune serum. CD4-DNA immune
      serum reacted with approximately 1/3 of freshly isolated lymphocytes but to very
      few cells in the CD4+ cells-depleted preparation. CD4-DNA immunized sera was used
      to enumerate CD4+ cells in the peripheral blood of 6 healthy donors and 2 AIDS
      patients. The number of CD4+ cells estimated by DNA immunized sera was very
      similar to estimates using standard anti-CD4 monoclonal antibody Leu3a. DNA-based
      immunization is therefore capable of raising antibodies to human leukocyte
      surface antigens. This technology may be useful for producing antibodies to other
      cell surface antigens in mice or other animals.

PMID- 9177824
TI  - Immunohistochemical characterization of a new monoclonal antibody reactive with
      dengue virus-infected cells in frozen tissue using immunoperoxidase technique.
AB  - This paper presents a novel monoclonal antibody shown to react with cytoplasmic
      antigens in various dengue infected human frozen organs from autopsy and necropsy
      specimens. Strong reactivity was found in hematopoietic cells, including
      immunoblasts, lymphocytes, plasma cells and macrophages of spleen, lymph node,
      lung, kidney and stomach. Strikingly, strong positivity was demonstrated in
      cerebral cortex neurones, Purkinje cells, choroid plexus and blood vessels in
      addition to astrocytes and microglia. Neurotropism of the virus could explain the
      meningitis, encephalitis, mononeuropathy and polyneuropathy observed by direct
      toxicity, but noted especially after an activation of mononuclear phagocytes and
      amplification of the immune response with subsequent vascular inflammation and
      formation of immune complexes.

PMID- 9177825
TI  - AIDS--associated Kaposi's sarcoma: a rare entity at Maharaj Nakorn Chiang Mai
      Hospital.
AB  - Kaposi's sarcoma [KS] is rare in Asian countries. Since the AIDS epidemic, KS has
      become the most common AIDS-related cancer reported in the international
      literature. Up to March 1996, 4 cases of AIDS-associated KS were histologically
      documented at the registry at the Maharaj Nakorn Chiang Mai University Hospital,
      comprising 2 adult and 2 pediatric male patients. Routes of HIV exposure included
      intravenous injection and heterosexual contact in adult cases, and perinatal
      transmission and blood transfusion in the pediatric ones. KS was present as an
      AIDS diagnostic condition in one of the adults and in both children. In our
      institution, KS was second in frequency to malignant lymphoma among AIDS
      patients. Predomination of non-homosexual transmission of HIV infection in this
      region was probably a factor associated with the rarity of AIDS-associated KS.

PMID- 9177826
TI  - V3 peptide enzyme immunoassay for serotyping HIV-1 infected pregnant Thais.
AB  - Previous molecular epidemiological studies show that at least 2 subtypes of HIV-1
      circulate in Thailand. HIV-1 subtype B or Thai genotype B was associated with an
      early epidemic and was prevalent in intravenous drug users. Meanwhile, HIV-1
      subtype E or Thai genotype A was becoming widespread among heterosexuals. We
      studied the HIV subtypes of 161 HIV-1 seropositive pregnant women. Of these, 143
      pregnant patients (88.8%) tested positive for subtype E alone and 8 women (5.0%)
      had evidence of infection with subtype B alone. There was serologic evidence of
      infection with a mixture of subtypes in 7 women while the infecting subtype could
      not be identified in the remaining 3 women. This result agrees with previous
      information that subtype E predominates in Thai heterosexuals.

PMID- 9177827
TI  - The prevalence of antinuclear, anti-dsDNA, anti-Sm and anti-RNP antibodies in a
      group of healthy blood donors.
AB  - We studied the prevalence of antinuclear (ANA), anti-double stranded DNA (dsDNA),
      anti-Sm and anti-RNP antibodies in a group of 93 blood donors (age range: 18-58
      years). Antinuclear and anti-ds DNA antibodies were detected by
      immunofluorescence (IF) using HEp2 cells and Crithidia luciliae as substrates,
      respectively, while anti-Sm and anti-RNP antibodies were assayed by ELISA. ANA
      was found in 6.5% while anti-dsDNA antibodies were not detected in any of the
      subjects. The 98th percentile was used as cut off where values greater than 0.651
      for anti-Sm and 0.601 for anti-RNP antibodies were taken to be positive. This
      gives a frequency of 1.1% for both antibodies. There was no significant
      association of antibody positivity with sex or race. We conclude that certain
      autoantibodies are present in low titres in the normal Malaysian Individuals, at
      a different frequency compared to other studies probably due to genetic, ethic or
      environmental factors.

PMID- 9177828
TI  - Prevalence of anti-varicella zoster IgG antibody in undergraduate students.
AB  - Sera from 74 healthy Thai undergraduate students, mean age 21 + 1.7 years, were
      tested for the presence of IgG antibody against varicella zoster virus (anti-VZV
      IgG) by ELISA. Fifty-five of 74 (74.3%) individuals possessed anti-VZV IgG
      antibody. The presence of anti-VZV IgG was associated with a past history of
      varicella (p < 0.005, X2 = 33.4989). No sexual preponderance was observed. We
      therefore found that 1 of 4 Thai young adults was susceptible to VZV infection.

PMID- 9177829
TI  - Syntheses of haptens containing dioxaphosphorinan methoxyacetic acid linker arms
      for the production of antibodies to organophosphate pesticides.
AB  - Four generic heterobifunctional reagents, namely 2-(2-chloro-5-methyl-1,3,2
      dioxaphosphorinan-5-yl)methoxyacetic acid methyl ester, p-sulfide, 2-(2-chloro-5
      methyl-1,3,2-dioxaphosphorinan-5-yl)-methoxyacetic acid methyl ester, p-oxide, 2
      (2-mercapto-5-methyl-1,3,2-dioxaphosphorinan-5-yl)-methoxyacetic acid
      bispotassium salt, p-sulfide-, and (2-methoxy-5-methyl-1,3,2-dioxaphosphorinan-5
      yl)methoxyacetic acid, methyl ester, have been synthesized and used to prepare
      organophosphate, thiophosphate, and dithiophosphate haptens containing a
      functional carboxyl group which can be used to conjugate the haptens to proteins.
      These hapten-protein conjugates have been used as antigens for preparing
      polyclonal sera against all classes of organophosphate pesticides. The eight
      examples used protein-hapten conjugates of chlorpyrifos, parathion, diazinon,
      paraoxon, azinphos, dimethoate, demeton, and dichlorvos. These were all
      immunogenic and resulted in sera containing antibodies that recognized the
      corresponding parent pesticide with high specificity.

PMID- 9177830
TI  - DNA binding and cleavage by a cationic manganese porphyrin-peptide nucleic acid
      conjugate.
AB  - A cationic manganese porphyrin-peptide nucleic acid (PNA) conjugate has been
      prepared and used to cleave a double-stranded DNA target. Cleavage experiments
      were performed with a 247-base pair restriction DNA fragment containing a 10-base
      pair homopurine binding target for the PNA. Oxidative activation by this Mn
      porphyrin-PNA conjugate leads to sequence specific, 3'-staggered cleavage of both
      DNA strands near the strand displacement junction. Furthermore, the Mn porphyrin
      PNA porphyrin conjugates bind over 100-fold better to double-stranded DNA
      compared to the native PNA.

PMID- 9177831
TI  - Nucleosides and nucleotides. 160. Synthesis of oligodeoxyribonucleotides
      containing 5-(N-aminoalkyl)carbamoyl-2'-deoxyuridines by a new postsynthetic
      modification method and their thermal stability and nuclease-resistance
      properties.
AB  - Heptadecadeoxynucleotides containing 5-(N-aminoethyl- or N-aminohexyl)carbamoyl
      2'-deoxyuridines (E or H) were synthesized using a newly developed postsynthetic
      modification method. As a convertible nucleoside unit, 5-methoxycarbonyl-2'
      deoxyuridine (1) was initially incorporated into oligodeoxynucleotides (ODNs)
      according to the phosphoramidite method at various positions using a DNA
      synthesizer. Fully protected ODNs attached to a solid support were treated with
      alkyldiamines such as ethylenediamine and 1,6-hexanediamine to give the above
      modified ODNs. The thermal stability, resistance toward nuclease digestion, and
      stability in fetal calf serum of the modified ODNs were studied. An increase in
      the number of 5-(N-aminohexyl)carbamoyl-2'-deoxyuridines (H) in the ODNs was
      found to effectively stabilize duplex formation with both the corresponding
      complementary DNA and RNA and protect against nucleolytic hydrolysis by snake
      venom phosphodiesterase. In particular, the half-life of ODN 19, which contained
      four H residues, was about 162 h in the presence of the nuclease. Furthermore, 19
      was also stable in medium containing 10% fetal calf serum with a t1/2 of about 48
      h, while t1/2 for the corresponding unmodified ODN was 13 min.

PMID- 9177832
TI  - Synthesis of conjugates for a barbiturate screening assay.
AB  - Novel derivatives of barbiturates functionalized with free carboxylic acids were
      designed and synthesized. Coupling of 5-cyclopentyl-5-carboxycrotylbarbituric
      acid via its active ester to an aminofluorescein derivative produced a
      fluorescent tracer. Conjugation of the 5-cyclopentenyl-5-carboxyethylbarbituric
      acid via its mixed anhydride to thyroglobulin allowed for subsequent development
      of a polyclonal antibody which was evaluated for binding in a fluorescence
      polarization immunoassay format with various barbiturates. The binding studies
      showed good cross-reactivity of a variety of barbiturates containing both
      aromatic and aliphatic 5-substituents with the tested antisera. The relationship
      between the immunogen architecture, the chemical structure of the binding
      analytes, and the characteristics of the antisera is also presented.

PMID- 9177833
TI  - Radiolabeling of epidermal growth factor with 99mTc and in vivo localization
      following intracerebral injection into normal and glioma-bearing rats.
AB  - High grade gliomas may have amplified expression of the epidermal growth factor
      receptor (EGFR) gene c-erb-B, which often is associated with increased expression
      of transmembrane EGFR. The purpose of the present study was to develop a method
      for labeling EGF with 99mTc and to determine whether the resulting radioligand
      would localize, following intracerebral injection, in rats bearing EGFR-positive
      gliomas. EGF has a relatively low molecular mass (approximately 6 kDa) compared
      to monoclonal antibodies, and this has allowed smaller bioconjugates, which
      should diffuse more rapidly within the brain and more effectively target
      disseminated glioma cells, to be constructed. In the present study, EGF has been
      labeled with either 131I or 99mTc, and in vitro uptake of the resulting
      radioligand has been investigated using C6EGFR rat glioma cells, which had been
      transfected with the EGFR gene. Cellular uptake of 131I radioactivity peaked
      after approximately 30 min of incubation with [131I]EGF, following which time it
      declined, while 99mTc radioactivity continued to increase over a 6 h incubation
      with [99mTc]-EGF. To determine if radiolabeled EGF had in vivo tumor-localizing
      properties, C6EGFR glioma cells were implanted stereotactically into the brains
      of Fischer rats. Four weeks later, either 99mTc- or 131I-labeled EGF was injected
      intracerebrally into normal or glioma-bearing animals using the same stereotactic
      coordinates. External gamma scintigraphy revealed that 131I radioactivity
      disappeared rapidly from the brain regions of tumor-bearing animals compared to
      99mTc, approximately 50% of which remained in the tumor for up to 12 h. In
      contrast, only approximately 20% remained in the brains of non-tumor-bearing
      animals after 6 h. These studies are the first to describe a method for
      radiolabeling EGF with 99mTc and to detect it by external scintigraphy in the
      brains of tumor-bearing animals.

PMID- 9177834
TI  - Synthesis of a new photoreactive derivative of dipyridamole and its use in the
      manufacture of artificial surfaces with low thrombogenicity.
AB  - Photoimmobilization of dipyridamole (Persantin) was accomplished through the use
      of a new synthetic conjugate molecule, 1. Persantin is a powerful inhibitor of
      platelet activation and aggregation and is widely used as a vasodilator.
      Conjugate 1 consists of triply protected dipyridamole [three of the four hydroxyl
      groups carry a tert-butyldimethylsilyl (TBDMS) protective group) and the
      photoreactive 4-azidobenzoyl group. A short hydrophilic spacer chain, derived
      from triethylene glycol, separates the protected dipyridamole system and the
      photoreactive group. Compound 1 was immobilized on polyurethane sheets
      (Pellethane D-55) through irradiation with ultraviolet (UV) light, and the
      protective groups were removed afterward. The resulting modified polyurethane
      surfaces were characterized by different physicochemical techniques: UV
      extinction, contact angle measurements (captive bubble technique), and X-ray
      photoelectron spectroscopy (XPS). The UV extinction measurements showed the
      presence of 13 +/- 1 nmol of immobilized dipyridamole/cm2. The contact angle
      measurements revealed that the modified surface was markedly more hydrophilic
      than the control (i.e. unmodified polyurethane). XPS measurements clearly
      established the presence of immobilized dipyridamole in the outermost layers of
      the modified surface. This was especially clear from the XPS spectra recorded at
      a low take-off angle (approximately 6 degrees). Furthermore, the XPS spectra
      showed that the TBDMS protective groups had been quantitatively removed during
      the deprotection/washing treatment. The in vitro blood compatibility of the
      modified surface was studied with the thrombin generation assay as developed in
      our group, as well as with scanning electron microscopy. The thrombin generation
      test produced a lag time of 1275 s for the modified surface, as opposed to 569 s
      for the control. Scanning electron microscopy showed that far fewer platelets
      adhere to the modified surface (approximately 7 x 10(3)/mm2) as compared to the
      control (approximately 6 x 10(2)/mm2). Taken together, the experimental data
      reveal that the modified surface has excellent blood compatibility in vitro. It
      is discussed that the use of conjugate 1 leads to simultaneous exposure of
      dipyridamole at the modified surface and to a marked increase of the surface
      hydrophilicity, which is likely to hamper adsorption of plasma proteins. The
      combination of these effects is uniquely related to the molecular buildup of 1.
      Conjugate 1 will be used in future work that is aimed at preparing small-caliber
      polyurethane vascular grafts with a blood compatible lumenal surface.

PMID- 9177835
TI  - 99mTc-labeled sigma-receptor-binding complex: synthesis, characterization, and
      specific binding to human ductal breast carcinoma (T47D) cells.
AB  - sigma-Receptors have recently been shown to be expressed in a variety of human
      tumor cells. In an attempt to prepare 99mTc chelates that would bind to sigma
      receptors and be useful for imaging sigma-receptor-positive tumors, we have
      synthesized and characterized a bisaminothiol (BAT) chelate appended with a sigma
      receptor pharmacophore. The synthesis of target ligand VII was accomplished in
      three steps starting from bicyclic imidazolidino[1,2-d]dithiazapine. The labeling
      of the BAT ligand with 99mTc was carried out in high yields (> 80%) using
      stannous tartarate as a reducing agent, resulting in the target sigma-receptor
      binding chelate [99mTc]BAT-EN6, III. Similarly, 99gTc chelate with ligand VII was
      prepared from ammonium pertechnetate by reduction with stannous tartarate. 99nTc
      radiolabeled chelate was purified by reversed phase HPLC, and cell binding with
      human breast ductal carcinoma (T47D) was performed. A high degree of specific
      binding (90-97%) was obtained when sigma-receptor ligands such as halogenated
      phenylethylenediamines were used to determine nonspecific binding. A modest
      affinity dose-dependent inhibition of binding was found with BD1008, I, and 4
      IPEMP, II (IC50 = 47 +/- 2 and 59 +/- 5 nM, respectively), known sigma-ligands.
      No specific binding was found with [99mTc]BAT, VIII [without appended sigma
      pharmacophore (N-alkyl-substituted ethylenediamine)], showing that biological
      activity resulted from the pendent pharmacophore. 99gTc complex was found to be a
      potent inhibitor (Ki = 42.7 +/- 8.5 nM) of [3H]DTG binding in guinea pig brain
      membranes. Scatchard analysis of [99mTc]BAT-EN6 (spiked with [99gTc]BAT-EN6)
      binding in T47D breast cancer cells showed a saturable binding, with a Kd of 43.5
      +/- 14.7 nM and a Bmax of 3121 +/- 130 fmol/(mg of protein). A biodistribution
      study of [99mTc]BAT-EN6 chelates in Sprague Dawley rats showed hepatic clearance,
      as expected. A blocking study at 4 h postinjection using 2 mumol of BD1008 with
      [99mTc]BAT-EN6 showed a significant decrease of radiopharmaceutical in liver
      (15.32 vs 22.31% ID/organ) and kidney (1.01 vs 2.21% ID/ organ), organs known to
      possess high concentrations of sigma-receptors. These results imply that
      [99mTc]BAT-EN6 binds with high affinity to sigma-receptors expressed in human
      breast tumor cells, and it may be useful for imaging breast cancer.

PMID- 9177836
TI  - Critical parameters for adduct formation of the carcinogen (+)-anti
      benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide with oligonucleotides.
AB  - Various parameters relevant for the formation of dG adducts produced in the
      reaction of individual benzo[a]pyrene diol epoxide (BPDE) stereoisomers with
      oligonucleotides have been studied. Reaction time, temperature, pH, molar ratio
      of diol epoxide and oligonucleotide, base sequence, and buffer system were shown
      to affect the amount of (+)-anti-BPDE dG adducts formed. Optimum experimental
      conditions for dG adduct formation were different depending on the base sequence
      context of the oligonucleotide employed [5'-d(CCTATAGATATCC) or 5'
      d(CCTATTGCTATCC)]. In general, low temperature to allow a longer reaction time,
      slightly alkaline Tris-HCl (pH 7.5-8.0) or alkaline phosphate buffer (pH 11), low
      concentration of organic solvent, and a molar excess of (+)-anti-BPDE promote dG
      adduct formation with an oligonucleotide. Low incubation temperature and Tris-HCl
      buffer also favor dG adduct formation of (-)-anti-BPDE and both enantiomers of
      syn-BPDE to both 5'-d(CCTATAGATATCC) and 5'-d(CCTATTGCTATCC).

PMID- 9177837
TI  - A 15-base acridine-conjugated oligodeoxynucleotide forms triplex DNA with its IL
      2R alpha promoter target with greatly improved avidity.
AB  - Attachment of 6,9-diamino-2-methoxyacridine to the 5' end of a purine-rich
      oligodeoxynucleotide targeting a 15 bp oligopurine oligopyrimidine stretch in the
      promoter region of the interleukin-2 receptor alpha chain (IL-2R alpha) gene
      results in an approximately 500-fold increase in its triplex forming avidity as
      determined by both band shift assay and DMS footprinting (Kd lowered from 2.5
      microM to 5 nM). This oligonucleotide participates in Mg(2+)-dependent three
      stranded DNA formation in which it is oriented antiparallel relative to the
      purine strand of the target duplex as determined by acridine moiety sensitized
      photoreactivity with the target duplex DNA. The oligonucleotides used in these
      studies were synthesized with a 3-amino-2-hydroxypropyl group at the 3' end to
      protect against exonucleolytic degradation for future in vivo applications. The
      3'-amino group underwent partial removal, probably during the NaOH deprotection
      step. Both the 3'-amino and the 3'-free forms of the oligo have the same binding
      avidity and specificity. The interaction of the third strand with its target is
      sequence specific and can be essentially abolished by a point G-->T transversion
      4 bases away from the 3' end of the target oligopurine block or severely reduced
      by other mutations within the target duplex. Thus, the attachment of the acridine
      moiety to the 5' end of the oligonucleotide does not seem to substantially
      compromise the sequence specificity of binding. Additionally, the oligonucleotide
      composed of G and A nucleotides was found to be superior to the oligonucleotide
      containing G and T residues since the difference in avidity of binding to the
      same target site was 17-fold.

PMID- 9177838
TI  - New coupling reagents for the preparation of disulfide cross-linked conjugates
      with increased stability.
AB  - To improve the in vivo stability of disulfide-linked immunotoxins (ITs), a series
      of sterically hindered cross-linking reagents were designed and synthesized.
      These ligands are characterized by a thioimidate group linked to an S-acetyl
      thiol or a substituted aryldithio group. To select the reagent of choice, several
      aryldithio thioimidates, substituted with a methyl or a phenyl group adjacent to
      the disulfide, were analyzed in thiol-disulfide exchange reactions. Also analyzed
      were the following: (i) the stability and solubility of the linkers in aqueous
      solution, (ii) the rate of protein derivatization, and (iii) the steric hindrance
      due to methyl or phenyl group substituents toward cleavage of the disulfide bond
      by glutathione. Ethyl S-acetyl 3-mercaptobutyrothioimidate (M-AMPT) was chosen as
      reagent to prepare two types of stable disulfide-containing AR-3-gelonin
      conjugates (IT2 and IT3). IT2 was prepared by a 3-(4
      carboxamidophenyldithio)propionthioimidate (CDPT)-derivatized antibody coupled to
      the M-AMPT-derivatized gelonin to afford a conjugate characterized by the
      presence of a methyl group adjacent to the sulfide bond. In the IT3 conjugate, an
      M-AMPT-derivatized toxin was coupled to the antibody thiolated with M-AMPT and
      then activated with Ellman's reagent (DNTB). The in vitro and in vivo stabilities
      of the three immunoconjugates were assayed, respectively, (i) by adding an excess
      of glutathione and monitoring protein release and (ii) by studying their
      pharmacokinetic behaviors. The specificity and cytotoxicity of all ITs were
      analyzed on target and unrelated cell lines, and no significant differences in
      activity were observed. IT3, consisting of a symmetrical dimethyl-substituted
      disulfide bond, was substantially more stable in vivo (t1/2 beta = 88.3 h) than
      the corresponding IT2, characterized by a disulfide-protected monomethyl
      substituent bond (t1/2 beta = 60.2 h) compared to the unhindered conjugate IT1
      (t1/2 beta = 27.9 h). This family of cross-linking reagents therefore offers
      advantages, such as minimal perturbation of the protein structure and controlled
      reactivity due to the thioimidate moiety, as well as the capacity to yield
      immunotoxins possessing substantial stability in vivo.

PMID- 9177840
TI  - Synthesis and characterization of rhenium-complexed alpha-melanotropin analogs.
AB  - Receptor binding peptides labeled with medically important radionuclides such as
      technetium and rhenium are an important tool for the imaging and treatment of
      many forms of cancer. This paper describes a method of labeling peptides with
      rhenium using a natural amino acid chelating moiety. The structural
      characteristics of this chelate moiety, N-acetyl-cysteine-glycine-cysteine
      glycine (NAc-CGCG) complexed with nonradioactive rhenium, have been investigated.
      The stability of this peptide-metal complex has been evaluated on the tracer
      level using radioactive rhenium-186. The rhenium-bound peptide has been appended
      to the N termini of receptor binding alpha-melanocyte stimulating hormone (alpha
      MSH, NAc-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) fragments via
      solid phase peptide synthesis. Bioassays and receptor binding studies of the
      resulting complexes demonstrate that the fragments retained biological activity
      and exhibited receptor binding constants ranging from 0.3 to 1.1 nM. This method
      could provide a general means of labeling bioactive peptide fragments that would
      simplify product purification and characterization.

PMID- 9177839
TI  - Single-chain Fv/folate conjugates mediate efficient lysis of folate-receptor
      positive tumor cells.
AB  - Bispecific antibodies that bind to a tumor antigen and the T cell receptor (TCR)
      redirect cytotoxic T lymphocytes (CTL) to lyse tumor cells which have escaped
      normal immune recognition mechanisms. One well-characterized tumor antigen, the
      folate receptor (FR), is expressed on most ovarian carcinomas and some types of
      brain cancer. Recently, it was shown that conjugates of folate and anti-TCR
      antibodies are extremely potent bispecific agents that target tumor cells
      expressing the high-affinity folate receptor, but not normal cells expressing
      only the reduced folate carrier protein. In this paper, it is shown that the size
      of these conjugates can be reduced to the smallest bispecific agent yet described
      (30 kDa) by attaching folate to a single-chain antibody, scFv, of the anti-TCR
      antibody KJ16. The scFv/folate conjugates are as effective as IgG/folate
      conjugates in mediating lysis of FR4 tumor cells by CTL. The optimal folate
      density was in the range of 5-15 folate molecules per scFv or IgG molecule, which
      yielded half-maximal lysis values (EC50) of approximately 40 pM (1.2 ng/mL for
      scFv). Finally, the scFv/folate conjugates could efficiently target tumor cells
      even in the presence of free folic acid at concentrations that are normally found
      in serum. Compared to conventional bispecific antibodies, the small size of
      scFv/folate conjugates may prove advantageous in the ability to penetrate tumors
      and in reduced immunogenicity.

PMID- 9177841
TI  - Kinetic analysis of sequence-specific alkylation of DNA by pyrimidine
      oligodeoxyribonucleotide-directed triple-helix formation.
AB  - Attachment of a nondiffusible bromoacetyl electrophile to the 5-position of a
      thymine at the 5'-end of a pyrimidine oligodeoxyribonucleotide affords sequence
      specific alkylation of a guanine base in duplex DNA two base pairs to the 5'-side
      of a local triple-helical complex. Products resulting from reaction of 5'
      ETTTTMeCTTTTMeCMeCTTTMeCTTTT-3' at 37 degrees C with a 29 base pair target duplex
      are determined by a gel mobility analysis to be oligonucleotides terminating in
      5'- and 3' -phosphate functional groups, consistent with a mechanism involving
      alkylation, glycosidic bond cleavage, and base-promoted strand cleavage. The
      guanine-(linker)-oligonucleotide conjugate formed upon triple-helix-mediated
      alkylation at the N7 position of a guanine base in a 60 base pair duplex was
      identified by enzymatic phosphodiester hydrolysis of the alkylation products
      followed by reversed phase HPLC analysis. To determine the rate enhancement
      achieved by oligonucleotide-directed alkylation of duplex DNA, a comparison of
      rates of alkylation at N7 of guanine in double-stranded DNA by the N
      bromoacetyloligonucleotide and 2-bromoacetamide was performed by a polyacrylamide
      gel assay. The reaction within the triple-helical complex on a restriction
      fragment was determined at 200 nM N-bromoacetyloligonucleotide to have a first
      order rate constant k1 of (2.7 +/- 0.5) x 10(-5) S(-1) (t1/2 = 7.2 h). The
      reaction of 2-bromoacetamide with a 39 base pair duplex of sequence corresponding
      to the restriction fragment targeted by triple-helix formation was determined to
      have a second-order rate constant k2 of (3.6 +/- 0.3) x 10(-5) M(-1) S(-1). A
      comparison of the first-order and second-order rate constants for the
      unimolecular and bimolecular alkylation reactions provides an effective molarity
      of 0.8 M for bromoacetyl within the triple-helical complex.

PMID- 9177842
TI  - Biodistribution and catabolism of Ga-67-labeled anti-Tac dsFv fragment.
AB  - The disulfide-linked fragment (dsFv) of the antibody to the alpha subunit of the
      IL2 receptor has been radiolabeled with a [Ga-67] Ga-2-(p-SCN-Bz)-NOTA derivative
      linked through an isothiocyanato group to either the epsilon-amino group of
      lysine or the alpha-amino group of the N-terminal amino acids. This low molecular
      weight protein (LMWP) has been proposed as a tumor diagnostic agent. However, >
      60% of the injected dose localized in the mouse kidney. The major catabolites (>
      95%) in the kidney were identified as the Ga-2-(p-SCN-Bz)-NOTA conjugate with
      either lysine or methionine, with no evidence of transchelation of Ga-67. Since
      different amino acids in the dsFv were radiolabeled according to this procedure,
      it was possible to study the relative residence times of the various catabolites.
      The methionine conjugate had a significantly shorter residence time than the
      lysine conjugate in the same kidney. Labeling the appropriate amino acid in a
      LMWP may lead to reduced residence times and increased diagnostic or therapeutic
      ratios.

PMID- 9177843
TI  - Regiospecific solid-phase synthesis of branched oligonucleotides. Effect of
      vicinal 2',5'- (or 2',3'-) and 3',5'-phosphodiester linkages on the formation of
      hairpin DNA.
AB  - A general procedure for the solid-phase regiospecific synthesis of branched
      oligonucleotides (bNA) analogues using readily available phosphoramidite reagents
      has been developed. The key feature of this method is use of the solid-phase
      phosphoramidite procedure to assemble linear oligonucleotide sequences and
      sequential removal of the phosphate (beta-cyanoethyl or methyl) and silyl
      protecting groups without detaching the nascent oligonucleotide from the solid
      support. Conversion of the phosphate backbone into the more stable phosphodiester
      linkages allows for removal of the 2'-O-tert-butyldimethylsilyl protecting group
      without cleavage or isomerization at the branch point. This method allows for the
      formation of branched oligonucleotides with sequences of arbitrary base
      composition, length, and orientation around the branch point junction, including
      a "Y"-shaped octadecamer d(TACTA)-rA[2',5'd(GTATGT)]3',5'd(CAAGTT). Studies to
      explore structural effects in the use of a branched adenosine as replacement for
      nucleotide loops in duplex and triplex DNA are also described. Branched
      oligonucleotides of the type rA[2',5'dCndA10-5']3',5'dCndT10-3' and
      rA[2',5'dCn3',3'dA10-5']3',5'dCnT10-3' form hairpin duplexes with thermal
      stability comparable to or better than that of one with a natural deoxynucleotide
      loop.

PMID- 9177844
TI  - Detection of oligonucleotide hybridization on a single microparticle by time
      resolved fluorometry: hybridization assays on polymer particles obtained by
      direct solid phase assembly of the oligonucleotide probes.
AB  - Oligodeoxyribonucleotides were assembled by conventional phosphoramidite
      chemistry on uniformly sized (50 microns) porous glycidyl methacrylate/ethylene
      dimethacrylate (SINTEF) and compact polystyrene (Dynosphere) particles, the
      aminoalkyl side chains of which were further derivatized with DMTrO-acetyl
      groups. The linker was completely resistant toward ammonolytic deprotection of
      the base moieties. The quality of oligonucleotides was assessed by repeating the
      synthesis on the same particles derivatized with a cleavable ester linker. The
      ability of the oligonucleotide-coated particles to bind complementary sequences
      via hybridization was examined by following the attachment of oligonucleotides
      bearing a photoluminescent europium(III) chelate to the particles. The
      fluorescence emission was measured directly on a single particle. The effects of
      the following factors on the kinetics and efficiency of hybridization were
      studied: number of particles in a given volume of the assay solution, loading of
      oligonucleotide on the particle, concentration of the target oligonucleotide in
      solution, length of the hybridizing sequence, presence of noncomplementary
      sequences, and ionic strength. The fluorescence signal measured on a single
      particle after hybridization was observed to be proportional to the concentration
      of the target oligonucleotide in solution over a concentration range of 5 orders
      of magnitude.

PMID- 9177845
TI  - Synthesis of new d-propoxyphene derivatives and the development of a
      microparticle-based immunoassay for the detection of propoxyphene and
      norpropoxyphene.
AB  - The synthesis of [S-(R,S)]-4-[[methyl[2-methyl-3-(1-oxopropoxy)-3, 4
      diphenylbutyl]amino]-1-oxobutoxy]-2,5-pyrrolidinedione+ ++ (propoxyphene active
      ester, 2) is described. This was used as an intermediate to prepare a
      propoxyphene immunogen, [S-(R,S)]-4-[methyl][2-methyl-3-(1-oxopropoxy)-3,4
      diphenylbuty l]-amino]- 1-oxobutyl-Bovine Thyroglobulin (3). This immunogen was
      then used to generate antibodies which demonstrate good cross-reactivity to d
      propoxyphene, d-norpropoxyphene, and other propoxyphene metabolites. In addition,
      these antibodies were shown to have very low cross-reactivity to methadone, a
      structurally related compound. The introduction of an aminomethyl benzoate spacer
      into the propoxyphene active ester (2), followed by the activation of the
      carboxylic acid, provided for a more stable active ester (5). This stable active
      ester, together with the antibodies generated from the propoxyphene immunogen,
      has led to the development of an immunoassay based on the Kinetic Interaction of
      Microparticles in Solution (KIMS).

PMID- 9177846
TI  - Structural determination of the conjugate of human serum albumin with a mitomycin
      C derivative, KW-2149, by matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - A new mitomycin C derivative, KW-2149, is known to form a covalent conjugate with
      human serum albumin (HSA). This conjugate exhibits 1/20 of the anticellular
      activity of unconjugated KW-2149. Structural studies of this conjugate were
      carried out using a combination of enzymatic digestion, high-performance liquid
      chromatography (HPLC), and matrix-assisted laser desorption/ionization (MALDI)
      mass spectrometry. The tryptic peptide T5 (residues 21-41) was the only peptide
      found to be modified by KW-2149 moieties, the [(gamma-L-glutamylamino)ethyl]thio
      group or the (2-aminoethyl)thio group, through a disulfide bond. Although the
      latter peptide lost its mitomycin C moiety in the course of tryptic digestion,
      these data strongly suggest that KW-2149 was bound to Cys-34, the only free
      cysteine on HSA.

PMID- 9177847
TI  - Electrospray mass spectrometry of alpha and beta chains of selected hemoglobins
      and their TNBA and TNB conjugates.
AB  - The molecular weights of alpha and beta hemoglobin chains from 15 different
      vertebrate animal sources and 2 common human variants were determined by
      electrospray mass spectrometry and compared to the calculated masses based on
      published amino acid sequences. Conjugates were prepared for 14 of the globins
      using 2 traditional colorimetric derivatizing reagents, 5,5'-dithiobis(2
      nitrobenzoic acid) (DTNB) and trinitrobenzenesulfonic acid (TNBS), and the mass
      of each conjugate was determined by mass spectrometry.

PMID- 9177848
TI  - Preparation, characterization, and biological evaluation of technetium(V) and
      rhenium(V) complexes of novel heterocyclic tetradentate N3S ligands.
AB  - Various tetradentate N3S ligands which contain pyridyl, morpholino, or imidazolyl
      moieties were prepared and labeled with technetium and rhenium. Metal
      complexation of the ligands occurred efficiently over the pH range from 2 to 11.
      Ligands possessing the S-THP (tetrahydropyranyl)-protected mercapto group labeled
      efficiently even under alkaline conditions, and among the three types of
      heterocyclic metal complexes, a marked difference in stability was observed;
      rhenium complexes decomposed to ReO4 whereas technetium complexes decomposed to
      TcO2/TcO4. In general, imidazolyl complexes of both technetium and rhenium were
      very stable in saline; less than 10% decomposition after 24 h. The technetium
      histidyl complex and technetium pyridyl complex were quite stable even under
      cysteine challenge; less than 10% decomposition after 24 h. The rhenium and
      technetium morpholino complexes were very unstable; greater than 10%
      decomposition after only 1 h in saline and greater than 25% decomposition in 1 h
      under cysteine challenge. Profound pharmacokinetic differences among these metal
      complexes were also observed in rat biodistribution studies. The neutral pyridyl
      complexes exhibited high blood and liver uptake and slow clearance from these
      tissues. The replacement of a hydroxyl group by a carboxyl group, which resulted
      in an anionic complex at physiological pH, resulted in a dramatic decrease in
      blood and liver uptake. The neutral imidazolyl complex exhibited marked reduction
      in blood uptake and much faster clearance from blood and liver compared to the
      neutral pyridyl complex. Finally, the anionic histidyl complex, which contains
      both the imidazolyl and carboxyl groups, had the most favorable pharmacokinetic
      properties in that it exhibited very low blood, liver, and kidney uptakes and a
      rapid clearance from the body via the renal system. The combination of the high
      stability and favorable pharmacokinetic properties of the imidazolyl complexes
      should render them useful for targeted delivery of the medically important
      isotopes.

PMID- 9177849
TI  - Use of designed peptide linkers and recombinant hemoglobin mutants for drug
      delivery: in vitro release of an angiotensin II analog and kinetic modeling of
      delivery.
AB  - We have designed and tested specific peptide linkers for the glutathione-mediated
      reductive release of the angiotensin II analog N-acetyl-CGDKVYIHPF attached to
      recombinant human hemoglobin mutants by a disulfide bond. Inclusion of negatively
      charged residues decreased the rate of release by as much as 5-fold for the N
      terminal linker DCD when compared to that of the control linker CG. Two different
      surface cysteine mutants in the second domain of the alpha,alpha-chain of
      recombinant human hemoglobin, D75C and K16C, were examined for their effect on
      the release of peptide by reduced glutathione. The reaction of the D75C-peptide
      conjugate with glutathione for release of the peptide is slow, with a second
      order rate constant of 2.1 M-1 S-1, allowing the possibility of long term
      delivery. The rate of peptide release from the K16C vs the D75C mutant was
      decreased 15-fold. Thus, different peptide release rates can be obtained by
      changing both peptide linker residues and the surface location of peptide
      attachment. Kinetic modeling of this release using either measured or literature
      values for different parameters suggests boundary conditions for application to
      the in vivo release of peptidomimetics, small molecules, or other drugs bound to
      the hemoglobin surface.

PMID- 9177851
TI  - Peptide targeting and delivery across the blood-brain barrier utilizing synthetic
      triglyceride esters: design, synthesis, and bioactivity.
AB  - As an approach to the development of therapeutically useful peptide
      pharmaceuticals that can penetrate the blood-brain barrier, we have designed and
      demonstrated the application of a carrier-targeting system. We have developed a
      prodrug design strategy that is designed to utilize membrane-bound enzymes
      whereby release of a bioactive peptide from a highly lipophilic triglyceride
      peptide-carrier is achieved in situ, thus attaining high localized concentrations
      of the bioactive peptide. Following localization of such a system, normal
      peptidase and lipase action is utilized to release the active peptide (deltorphin
      II) intact and in high concentration. At present, the exact mechanisms are
      unclear, but the observed results in which analgesia is observed following
      peripheral administration suggest that the active peptide is able to cross the
      blood-brain barrier and sustain prolonged periods of analgesia as determined by
      antinociception tests by release of the bioactive peptide. In vitro tests of
      binding and bioactivity by the peptide conjugate show essentially no potency in
      either target or control analogues, but potent antinociceptive effects are
      observed following peripheral administration.

PMID- 9177850
TI  - Peptomer aluminum oxide nanoparticle conjugates as systemic and mucosal vaccine
      candidates: synthesis and characterization of a conjugate derived from the C4
      domain of HIV-1MN gp120.
AB  - Peptomers are polymers composed of peptides that are specifically cross-linked in
      a head-to-tail fashion. Recently, a peptomer composed of an amphipathic peptide
      from the C4 domain of HIV-1MN gp120 was shown to display a prominent alpha
      helical conformation that, as an immunogen, elicited rabbit antibodies
      recognizing native and recombinant gp120 [Robey et al. (1995) J. Biol. Chem. 270,
      23918-23921]. For the present study, we synthesized a conjugate composed of the
      C4 peptomer covalently linked to calcinated aluminum oxide nanoparticles. The
      nanoparticles were first reacted with (3-aminopropy])-triethoxysilane to provide
      an amine load of 15.9 mmol of R-NH2/g of solid. The amine-modified aluminum oxide
      nanoparticles then were reacted with N-acetylhomocysteine thiolactone at pH 10 to
      place a reactive thiol on the nanoparticles. A bromoacetylated C4 peptomer,
      modified at the epsilon-amines of lysine residues, then was reacted with the
      thiolated nanoparticles to give the peptomer covalently linked to aluminum oxide
      via a thioether bond. The peptomer load was determined to be 16 mg of peptomer/g
      of particles, a 55% theoretical yield. Particle shape and size of the peptomer
      conjugated alumina were analyzed by electron microscopy and displayed a mean
      maximum diameter of 355 nm and a mean minimum diameter of 113 nm, well within the
      desired size range of 300 nm believed to be optimal for mucosal immunization
      purposes. Experimentally determined values of mean particle diameters, specific
      surface area, and specific peptomer load provided the information necessary to
      calculate the mean antigen load, which was determined to be 53000 +/- 42000
      peptomer epitopes per particle. Peptomer-alumina conjugates, such as that
      described here, could form the basis of a new class of biomaterial that combines
      a chemically defined organic immunogen with a nontoxic chemically defined
      inorganic adjuvant.

PMID- 9177852
TI  - Conventional and high-yield synthesis of DTPA-conjugated peptides: application of
      a monoreactive DTPA to DTPA-D-Phe1-octreotide synthesis.
AB  - Successful imaging of somatostatin receptor-positive tumors with 111In-DTPA-D
      Phe1-octreotide has stimulated development of peptide radiopharmaceuticals using
      DTPA as the chelating agent. However, use of cyclic DTPA dianhydride (cDTPA)
      resulted in low synthetic yields of DTPA-peptide by either solution or solid
      phase syntheses. This paper reports a novel high-yield synthetic procedure for
      DTPA-D-Phe1-octreotide that is applicable to other peptides of interest using a
      monoreactive DTPA derivative. A monoreactive DTPA that possesses one free
      terminal carboxylic acid along with four carboxylates protected with tert-butyl
      ester (mDTPA) was synthesized. Fmoc-Thr(tBu)-ol, prepared from Fmoc-Thr(tBu)-OH,
      was loaded onto 2-chlorotrityl chloride resin. After construction of the peptide
      chains by Fmoc chemistry, mDTPA was coupled to the alpha amine group of the
      peptide on the resin in the presence of 1,3-diisopropylcarbodiimide and 1
      hydroxybenzotriazole. Treatment of the mDTPA-peptide-resin with trifluoroacetic
      acid-thioanisole removed the protecting groups and liberated [Cys(Acm)2,7]
      octreotide-D-Phe1-DTPA from the resin. Iodine oxidation of the DTPA-peptide,
      followed by the reversed-phase HPLC purification, produced DTPA-D-Phe1-octreotide
      in overall 31.8% yield based on the starting Fmoc-Thr(tBu)-ol-resin. The final
      product gave a single peak on analytical HPLC, and amino acid analysis and mass
      spectrometry confirmed the integrity of the product. 111In radiolabeling of the
      product provided 111In-DTPA-D-Phe1-octreotide with > 95% radiochemical yield, as
      confirmed by analytical reversed-phase HPLC, TLC, and CAE. These finding
      indicated that use of mDTPA during solid-phase peptide synthesis greatly
      increased the synthetic yield of DTPA-D-Phe1-octreotide, due to the absence of
      nonselective reactions that are unavoidable when cDTPA is used. These results
      also suggested that mDTPA would be a versatile reagent to introduce DTPA with
      high yield into peptides of interest.

PMID- 9177853
TI  - Heterobifunctional cross-linkers containing 4,9-dioxa-1,12-dodecanediamine
      spacers.
AB  - A series of heterobifunctional linker arms has been prepared by functionalization
      of (tert-butoxycarbonyl)-4,9-dioxa-1,12-dodecanediamine [tBOC-HN(CH2)3 O(CH2)4
      O(CH2)3 NH2] with anhydrides or acid chloride.

PMID- 9177854
TI  - Matrix collagen type and pore size influence behaviour of seeded canine
      chondrocytes.
AB  - This study directly compared the behaviour of chondrocytes in porous matrices
      comprising different collagen types and different pore diameters. There was a
      dramatic difference in the morphology of the cells in the type I and type II
      collagen matrices. The cells in the type II collagen matrix retained their
      chondrocytic morphology and synthesized glycosaminoglycans, while in the type I
      matrix the chondrocytes displayed a fibroblastic morphology with less
      biosynthetic activity than those in the type II. Small pore diameter affected
      morphology initially in the type I matrices and showed a higher increase of DNA
      content, but with time the cells lost the chondrocytic morphology. Our results
      demonstrate the marked influence of collagen type and pore characteristics on the
      phenotypic expression of seeded chondrocytes.

PMID- 9177855
TI  - Calcium phosphate ceramic coatings as carriers of vancomycin.
AB  - Infection in the setting of total joint arthroplasty remains a challenging
      problem. Attention has turned to developing methods of local delivery of
      antibiotics for prophylaxis. Vancomycin loaded into calcium phosphate ceramic
      coatings on titanium alloy substrates is a clinically relevant concept in the
      setting of total joint arthroplasty. Drug loading was accomplished by immersion
      of ceramic-coated discs in vancomycin-containing simulated physiological
      solution; in some experiments drug loading by immersion was followed by lipid
      coating in egg phosphatidylcholine solutions. The kinetics of vancomycin release
      and the efficacy of drug inhibition of Staphylococcus aureus were determined in
      vitro in comparison to the release from currently used antibiotic-laden
      poly(methyl methacrylate) (PMMA). The loading by immersion provided effective
      release and inhibition at early time points (up to 24 h); however, the lipid
      coated samples demonstrated significant release and effective bacterial
      inhibition up to 72 h. The two-step procedure, i.e. drug loading followed by
      lipid coating in order to slow antibiotic elution, is more effective than the
      conventional one-step loading. The study indicated that the osteoconductive
      calcium phosphate coatings have the potential to serve as drug carriers to
      prevent infection in the setting of total joint arthroplasty.

PMID- 9177856
TI  - Effect of different surface finishing and of hydroxyapatite coatings on passive
      and corrosion current of Ti6Al4V alloy in simulated physiological solution.
AB  - Direct and alternating current electrochemical tests were carried out on Ti6Al4V
      with different surface finishing and with hydroxyapatite (HA) coatings. Sand
      blasting and rough titanium deposits obtained by vacuum plasma spraying (VPS)
      bring about an increase of passive and corrosion current density (c.d.) with
      respect to smooth Ti6Al4V, as a consequence of the augmentation of the real
      surface. The presence of HA deposits obtained by VPS causes an increase of
      passive and corrosion c.d. of the metallic substrate of about one order of
      magnitude and this should be taken into account in view of human body
      applications.

PMID- 9177857
TI  - Structural and electrochemical examinations of PACVD TiO2 films in Ringer
      solution.
AB  - The conditions for obtaining titanium dioxide from the substrates titanium
      tetrachloride and oxygen and applying this to a surgical stainless steel of the
      type 316L by the plasma assisted chemical vapour deposition method have been
      determined. It was established that, during the process, titanium dioxide anatase
      is created, Crystallizing in a tetragonal lattice. During exposure of the 316L
      steel with the titanium dioxide coating, in Ringer's solution, protective
      properties of this covering improve. After 120 h the coating adopts superior
      barrier characteristics. Titanium dioxide covering increases the resistivity of
      steel of the type 316L to pitting corrosion and general corrosion. Any damage or
      partial removal of the coating does not cause an increased galvanic corrosion of
      the substrate.

PMID- 9177858
TI  - Rietveld analysis and Fourier maps of hydroxyapatite.
AB  - Rietveld analysis was applied to the X-ray powder diffraction data of well
      crystallized hydroxyapatites synthesized at 80 degrees C and pH 7.4. The least
      squares refinement program adopted for Rietveld analysis showed good pattern
      fitting with the calculated profile. The a- and c-axis dimensions, a-0.943046 +
      0.000126 nm and c-0.687485 +/- 0.000104 nm, were obtained and compared with the
      data estimated from a single peak. The lattice dimensions obtained by Rietveld
      analysis were much closer to the values of a single crystal, a = 0.9432 nm and c
      0.6881nm. Fourier analysis was also performed. The maps of electron densities
      expressed the existing possibility of each atom composing hydroxyapatite in the
      crystal structure. In particular, columnar calcium and screw-axis calcium were
      clearly revealed. These data agreed well with the computer graphics model of
      hydroxyapatite reported previously.

PMID- 9177859
TI  - Characterization of protein release through glucose-sensitive hydrogel membranes.
AB  - Glucose-sensitive phase-reversible hydrogels have been prepared based on the
      specific interaction between polymer-bound glucose and concanavalin A (Con-A).
      The main goal of this study was to characterize the release of model proteins
      (insulin and lysozyme) through the hydrogel membrane as the free glucose
      concentration in the environment was changed. The diffusion of the model proteins
      through the hydrogel membrane was examined using a diffusion cell. Porous
      poly(hydroxyethyl methacrylate) (PHEMA) membranes were used to sandwich the
      mixture of glucose-containing polymers and Con-A in between the donor and
      receptor chambers. The porous PHEMA membranes allowed diffusion of glucose,
      insulin and lysozyme, while preventing loss of glucose-containing polymers and
      Con-A in the sol state. The release rate of model proteins through the glucose
      sensitive hydrogel membrane was dependent on the concentration of free glucose.
      The release rate of the proteins did not remain constant, however, due to the
      change in free glucose concentration resulting from diffusion of glucose from the
      receptor chamber to the donor chamber. This study demonstrated the possibility
      that the glucose-sensitive phase-reversible hydrogels can be used to regulate the
      insulin release as a function of the free glucose concentration in the
      environment.

PMID- 9177860
TI  - Denatured thiolated collagen. I. Synthesis and characterization.
AB  - A new thiolating reagent is used to introduce sulphur groups into denatured
      atelocollagen. The procedure is easy to control and applicable on a large scale.
      The reagent is a reactive dicarboxylic acid compound containing sulphur in the
      form of a disulphide functionality. It is prepared by reacting N,N'
      disuccinoylcystamine with 1,1'-carbonyldiimidazole. When this reagent is added to
      a solution of denatured atelocollagen in dimethylsulphoxide, amide bonds are
      formed between the carbonyl functions of the reagent and epsilon-NH2 of lysine
      and hydroxylysine residues from the protein. The disulphide groups introduced can
      then be reduced by reaction with 1,4-dithiothreitol to give the-SH form of the
      modified protein. Control of the stoichiometry between the reagent and the
      protein can lead to varying modification levels. A maximum level of 0.33 mmol SH
      per gram of protein can be attained, which corresponds to complete thiolation of
      the lysine and hydroxylysine residues. Thiolated denatured atelocollagen exhibits
      gelatin-like behaviour, by being highly soluble in water at all pH values and by
      forming heat-reversible gels.

PMID- 9177861
TI  - Denatured thiolated collagen. II. Cross-linking by oxidation.
AB  - We have recently described a new method for the thiolation of denatured collagen,
      which allows precise amounts of SH groups to be attached onto the protein
      backbone. The oxidation of denatured thiolated collagen produces disulphide cross
      linking. The cross-linking of these products has been studied, optimized and
      compared to the cross-linking of native and denatured collagen with 0.5% aqueous
      glutaraldehyde. Films have been prepared and their tensile mechanical properties
      and biodegradation rates with trypsin and collagenase have been evaluated. Our
      results indicate that the cross-linking in oxidized thiolated collagen depends on
      the number of the disulphide bridges formed and on their intermolecular versus
      intramolecular repartition. Since the number of disulphide bridges can be
      controlled by the level of thiol in the denatured collagen and by the oxidation
      procedure, it is possible to control the mechanical properties and the
      biodegradation rates of these new materials. Under optimized conditions, oxidized
      denatured thiolated collagen films are more resistant and rigid than
      glutaraldehyde-cross-linked collagen films Cross-linked thiolated collagen
      materials are also more resistant to collagenase degradation. However, because of
      the loss of the triple-helical structure, they are more susceptible to trypsin
      degradation relative to glutaraldehyde-cross-linked triple-helical collagen.
      Denatured collagen cross-linked by physiological bridges such as disulphide
      bridges, with controllable mechanical properties and biodegradation rates, is of
      considerable interest in biomedical applications.

PMID- 9177862
TI  - Adsorption of alpha-1-microglobulin from biological fluids onto polymer surfaces.
AB  - A recent study in our laboratory has identified the potential role of urine
      derived alpha-1-microglobulin (alpha-1-m) in mediating Pseudomonas aeruginosa
      adhesion to polystyrene, while other workers have suggested a possible role of
      the protein in the immunological response. Due to the ubiquitous presence of
      alpha-1-m in body fluids, the adsorption of the protein from serum, cerebrospinal
      fluid, urine and used continuous ambulatory peritoneal dialysis fluid onto
      polystyrene was investigated. The treated surfaces were sequentially immersed in
      water and increasingly concentrated isopropanol-water solutions in order to
      selectively desorb bound proteins on the basis of their binding strength. Sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis of the wash supernatants
      showed different protein desorption profiles for each biological fluid, despite
      the qualitative similarity between the protein composition of the fluids, and
      highlighted the uptake of alpha-1-m from each fluid to the surface. In the case
      of urine, the analysis was extended to commercial polyurethane and silicone
      stents. The ease of desorption of urine-derived alpha-1-m could be correlated
      with surface hydrophobicity of the stent biomaterial.

PMID- 9177863
TI  - Rotated plywood structure of primary lamellar bone in the rat: orientations of
      the collagen fibril arrays.
AB  - A basic structural motif of lamellar bone is the arrays of parallel collagen
      fibrils, with successive arrays having different orientations to form a plywood
      like structure. Measurements of the angles between adjacent arrays from
      cryomicrotomed and vitrified thin sections of demineralized rat bone, cut
      approximately parallel to the lamellar boundary plane, show that most angles are
      around 30 degrees, although a subset are around 70 degrees. A structural model
      for collagen organization based on these measurements is proposed in which an
      individual lamellar unit (thick and thin lamellae together with transition zones)
      is composed of five arrays of parallel collagen fibrils, each offset by 30
      degrees.

PMID- 9177864
TI  - A murine model of human myeloma bone disease.
AB  - Myeloma causes a devastating and unique form of osteolytic bone disease. Although
      osteoclast activation is responsible for bone destruction, the precise mechanisms
      by which myeloma cells increase osteoclast activity have not been defined. An
      animal model of human myeloma bone disease would help in clarification of these
      mechanisms. Multiple myeloma occurs spontaneously in aging C57 BL/KaLwRij mice
      and has all of the features of the disease in humans, including the
      characteristic bone lesions. The disease can be induced in normal C57 BL/KaLwRij
      mice by inoculation of fresh marrow-derived cells from mice with myeloma, but
      this model is difficult to study because of variability in the number of myeloma
      cells in marrow-derived preparations. To develop a better animal model of human
      myeloma bone disease, we have established and subcloned a cell line from this
      murine myeloma and found that it causes osteolytic bone lesions in mice
      characteristic of human myeloma bone disease. The cell line produces interleukin
      6, but grows independent of exogenous interleukin-6. Mice inoculated
      intravenously with the cultured cells predictably develop an identical disease to
      the mice injected intravenously with fresh bone-marrow-derived myeloma cells,
      including monoclonal gammopathy and radiologic bone lesions. We found that some
      of the mice became hypercalcemic, and the bone lesions are characterized by
      increased osteoclast activity. We found identical results when we inoculated
      Nu/Bg/XID mice with cultured murine myeloma cells. Because we can inoculate mice
      with precise numbers of cells and predict accurately when the mice will develop
      bone lesions, become hypercalcemic, and die, this should be a convenient model
      for determining the mechanisms by which the myeloma cells cause osteoclast
      activation in this model of human myeloma bone disease.

PMID- 9177865
TI  - Systemic administration of an anabolic dose of PGE2 in young rats increases the
      osteogenic capacity of bone marrow.
AB  - Prostaglandin E2 (PGE2) possesses significant anabolic properties when
      administered systemically (i.e., it increases bone formation and, consequently,
      bone mass). We recently characterized the effects of a 3 week administration of 6
      mg/kg PGE2 into young rats and showed it increases cortical and cancellous bone
      mass and mechanical strength in long bones and bone density in the calvaria. We
      also found that a single dose of PGE2 induces the expression of early-response
      genes (c-fos, c-jun, and egr-1) in bone marrow cells within these two types of
      bone. These observations, together with findings by others of new cancellous bone
      formation in PGE2-treated animals, suggested that recruitment of osteoblasts from
      their precursors is a major mechanism of the anabolic effect of PGE2. To test
      this hypothesis directly, we injected PGE2 (6 mg/kg) or vehicle into 4-week-old
      rats for 2 weeks and then assessed the osteogenic potential of bone marrow in an
      ex vivo culture system. Primary and first-passage bone marrow cultures were
      established in the presence of beta-glycerophosphate, ascorbate, and
      dexamethasone, and osteogenic differentiation was measured by bone nodule
      formation and alkaline phosphatase activity. This regimen increased bone mass
      expressed as femoral ash weight by 4.7% and tibial cancellous bone area by 38.3%.
      Nodule formation at 21 days was increased in both primary and first-passage
      cultures from PGE2-treated rats despite seeding of the same number of marrow
      cells. Alkaline phosphatase activity was elevated in both primary and first
      passage cultures from PGE2-treated rats beginning 6-10 days after culture
      initiation. Cell proliferation was only slightly elevated in cultures from PGE2
      treated rats. These data strongly suggest that in vivo administration of PGE2
      induces the proliferation or differentiation of osteoprogenitor cells in bone
      marrow, and this effect takes a major part in its anabolic effect in vivo.

PMID- 9177866
TI  - Osteocytes and bone lining cells: which are the best candidates for mechano
      sensors in cancellous bone?
AB  - Previously, we have investigated the possible role of osteocytes as mechano
      sensors, and mediators of bone turnover. It was found that the proposed
      regulatory mechanism produced morphologies of trabecular bone, under particular
      loading conditions, which were consistent with morphogenesis and adaptation as
      seen in reality. The main objective of this study was to discern whether lining
      cells or osteoblasts could possibly play a similar role as effectively with
      regard to their capacity for self-optimization of the trabecular architecture, in
      terms of a low apparent mass to stiffness ratio. For that purpose the earlier
      analyses with osteocytes as mechano-sensors, distributed throughout the bone,
      were repeated for mechano-sensors located at bone surfaces only. Compared to the
      osteocyte model, the surface cell remodeling algorithm was reluctant to change
      its architecture, which implies that it is less sensitive to changes in the
      loading pattern. This resulted in less efficient bone adaptation, which was
      reflected by a considerably higher relative mass for a similar apparent stiffness
      in the loading direction. In other words, more mass is needed to obtain an
      equally stiff structure, at the apparent level, with respect to the externally
      applied loads. Furthermore, stresses and strains at the tissue level vary across
      a much wider range, relative to the osteocyte model, where the higher incidence
      of elevated strains indicates an increased failure risk. Therefore, we conclude
      that mechanical information at the bone surface may not be sufficient to
      adequately regulate functional bone adaptation.

PMID- 9177867
TI  - Expression of gelatinases within the trabecular bone compartment of
      ovariectomized and parathyroidectomized adult female rats.
AB  - Ovariectomized (ovx) and parathyroidectomized (ptx) rat models of disturbed bone
      metabolism have been widely used in evaluating bone changes resulting from
      hormonal depletion, and are characterized by elevated and depressed bone
      turnover, respectively. We report here the expression of gelatinases extracted
      from native trabecular bone in these models. Nine-month-old female Sprague-Dawley
      rats were sacrificed after 3 weeks following ovx or 10 days post ptx to determine
      the influence of these procedures on the levels of proximal tibial bone tissue
      gelatinases. Identification and quantitation of these enzymes were performed via
      gelatin gel zymography of native tissue extracts and laser densitometry of
      developed gels, respectively. In the ptx model, a reduction in tissue levels of
      pro- and active-MMP-2 and a 45 kDa activated fragment was seen, whereas ovx
      exhibited significant increases in these enzymes. The MMPs are therefore clearly
      under the influence of factors known to modulate bone remodeling in vivo. The
      study of MMP levels directly extracted from bone using these experimental models
      may assist in developing management regimes for metabolic bone diseases through
      the use of drugs aimed at controlling turnover.

PMID- 9177868
TI  - Long-bone biomechanics in mice selected for body conformation.
AB  - Two lines of mice divergently selected from the control strain (CBi) against the
      positive phenotypic correlation between body weight (b.w.) and tail (skeletal)
      length were obtained (CBi/C: high weight, short tail; CBi/L: low weight, long
      tail). The selected animals showed a different relationship between body and
      skeletal masses. To compare the adequacy between biomass and load-bearing ability
      of the skeleton, and to describe the eventual role of bone mechanostat in the
      production of these changes, cross-sectional and bending properties of both femur
      diaphyses were determined in CBi, CBi/C, and CBi/L adult mice of both genders.
      Cortical bone material quality (elastic modulus) was reduced in the selected
      lines (p < 0.001), significantly less in CBi/C than in CBi/L. In contrast, cross
      sectional design (b.w.-adjusted values of moment of inertia, CSMI) was largely
      improved (p < 0.001), significantly more in CBi/C than in CBi/L. These effects
      determined a greater stiffness and strength in CBi/C than in CBi/L or CBi weight
      paired mice. The elevations of the negative regression lines between elastic
      modulus and CSMI ("distribution/quality" curves) decreased in the order CBi/C >
      CBi/L > CBi. Data show that selection improved diaphyseal stiffness and strength
      in CBi/C animals because of an architectural overcompensation for the reduced
      bone material quality. Therefore, an inadequate control of long-bone
      architectural design as a function of the mechanical quality of cortical bone and
      b.w. bearing could have been induced in that line. Assuming bone mechanostatic
      regulation to be genetically programmed, some of the corresponding biological
      determinants should be transmitted independently, because artificial selection
      separately affected material quality and architectural design. The possibility of
      transmission of an inadequate mechanostatic function (inability to adapt bone
      modeling to bone material quality as a function of the biomass to be supported)
      was also shown, as some genotypes could express architectural modifications that
      largely exceed bone material quality deterioration.

PMID- 9177869
TI  - Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two
      humans.
AB  - The bone mineral density and the biochemical parameters exploring bone cell
      activities were analyzed in two cosmonauts who spent 1 and 6 months,
      respectively, in the Russian MIR station. Measurements were performed before the
      flight, after the flight, and after a recovery period. At the end of the first
      month, peripheral QCT measurements indicated a slight decrease of trabecular bone
      mass in the distal tibial metaphysis. However, after 6 months of spaceflight, a
      more marked loss of trabecular and cortical bones was observed in the tibia, and
      was still significant after 6 month recovery in the trabecular compartment,
      whereas a decrease was no longer observed in the cortical envelope. No change was
      observed in either compartment of the distal radius at any time. Ultrasound BUA
      of the calcaneus was greatly reduced by the first month, followed by a more
      dramatic decrease after month 6. Ultrasound SOS detected no change. Parameters
      reflecting bone formation activity appeared to be depressed after both missions.
      In contrast, no dramatic change in resorption parameters was observed, except for
      a trend toward an increase in pyridinoline. In conclusion, the lower weight
      bearing bones appeared more sensitive than the upper ones in terms of spaceflight
      induced bone loss. This probably explained the absence of marked systemic
      biochemical data changes. This study further suggests that recovery in the tibial
      trabecular compartment 6 months after landing was not completed after a 6 month
      mission.

PMID- 9177870
TI  - Evaluation of vertebral volumetric vs. areal bone mineral density during growth.
AB  - Bone mineral "density" (BMD) measured by dual-energy X-ray absorptiometry (DEXA)
      does not represent the volumetric density (grams per cubic centimeter), but
      rather the areal density (grams per square centimeter). This distinction is
      important during growth. The purpose of this study was to measure vertebral
      dimensions in cadavers of young pigtail macaques (Macaca nemestrina), and to
      derive equations to predict the volumetric bone density from noninvasive
      measurements. We measured the areal bone density by DEXA, vertebral volume by
      underwater weighing, mineral content by ashing, dimensions of lumbar vertebrae by
      calipers, and dimensions of vertebrae by radiography. Somatometric measurements
      of the female lumbar vertebral bodies showed that the shape changed during
      growth. The bone mineral content from the densitometer correlated significantly
      with the ash weight (r = 0.99, error 8.7%). The correlation coefficient between
      the volumetric bone mineral density and areal BMD measurement was significant (r
      = 0.68, p < 0.0001) with a 9.5% error; this improved significantly to 0.82 (7.2%
      error) when the BMD was divided by the vertebral depth from the radiograph. A
      real BMD showed a strong correlation with age (r = 0.82, p < 0.0001), with an
      average increase of 7.4%/year. In contrast, volumetric mineral density showed a
      weak relationship with age (r = 0.43, p < 0.01), for an average increase of
      1.5%/year. When studying bone mineral density during growth, the differences
      between volumetric and areal bone mineral density should be taken into
      consideration.

PMID- 9177871
TI  - 1-alpha-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium
      regulating hormones in early postmenopausal women.
AB  - 50 Japanese women within 10 years after menopause (mean age 52.5 years) were
      studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3
      [1-alpha-(OH)D3] with calcium (150 mg/day) (treated group: N = 25) and calcium
      only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2
      4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal
      women. L2-4 BMDs increased significantly in the treated group (+2.1%; p < 0.01),
      but decreased significantly in controls (-2.1%; p < 0.01). Although serum calcium
      and creatinine remained unchanged in both groups, phosphorus levels increased
      significantly in the treated group (p < 0.01). Urinary calcium/creatinine (Cr)
      increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr
      decreased significantly in the treated group (p < 0.05), but not in the control
      group. Serum osteocalcin levels remained unchanged in both groups. Intact
      parathyroid hormone levels decreased significantly (p < 0.05) and calcitonin
      levels significantly increased in the treated group (p < 0.05), but these changes
      were not observed in the control group. These data clearly demonstrate that 0.75
      microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by
      modulation of calcium-regulating hormones. Temporarily increased urinary calcium
      excretion was observed in control group, but did not appear to be effective in
      modulating bone turnover.

PMID- 9177872
TI  - Bone turnover in neonates: changes of urinary excretion rate of collagen type I
      cross-linked peptides during the first days of life and influence of gestational
      age.
AB  - New markers have been used to monitor the changes of bone turnover occurring
      during growth. Data on bone turnover rate during the perinatal period are,
      however, very scarce. In the present study we evaluated bone turnover rate,
      assessed by the measurement of urinary N-terminal telopeptide of type I collagen
      (NTx) concentrations, at different gestational ages, and we documented the trend
      of bone turnover rate occurring in the first days after birth. Urine samples were
      obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of
      diabetic mothers (IDMs). The first miction after birth was collected. Urine
      samples were also collected 24 and 48 h after birth. NTx was measured by an
      enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle,
      WA). The relationship between NTx at birth and all the other variables has been
      evaluated using multiple regression analysis. The changes of NTx excretion over
      time and the effect of the groups were studied by multivariate analysis of
      variance (MANOVA) for repeated measures. We found a remarkable association
      between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001).
      NTx concentrations showed a progressive decrement, reaching a nadir between the
      38th and the 42nd week of gestation. The NTx concentrations changed significantly
      during the first 48 h of life in the three groups. Moreover, preterm infants had
      NTx excretion values at birth significantly higher than full term infants (p <
      0.001), whereas NTx excretion rates of IDMs were not different from those of the
      other two groups of subjects. In conclusion, gestational age seems to be the
      major determinant of bone turnover in neonates; NTx excretion rate is higher
      before term, it slows in proximity of delivery, and it increases significantly
      during the first 48 h of life. Preterm infants have higher bone turnover rate
      than full term infants. NTx excretion rate of IDMs was comparable with those of
      the control subjects.

PMID- 9177873
TI  - A valuable international bridge to the rehabilitation of burn patients with
      facial disfigurement.

PMID- 9177874
TI  - Fluid resuscitation following a burn injury: implications of a mathematical model
      of microvascular exchange.
AB  - A validated mathematical model of microvascular exchange in thermally injured
      humans has been used to predict the consequences of different forms of
      resuscitation and potential modes of action of pharmaceuticals on the
      distribution and transport of fluid and macromolecules in the body. Specially,
      for 10 and/or 50 per cent burn surface area injuries, predictions are presented
      for no resuscitation, resuscitation with the Parkland formula (a high fluid and
      low protein formulation) and resuscitation with the Evans formula (a low fluid
      and high protein formulation). As expected, Parkland formula resuscitation leads
      to interstitial accumulation of excess fluid, while use of the Evans formula
      leads to interstitial accumulation of excessive amounts of proteins. The
      hypothetical effects of pharmaceuticals on the transport barrier properties of
      the microvascular barrier and on the highly negative tissue pressure generated
      postburn in the injured tissue were also investigated. Simulations predict a
      relatively greater amelioration of the acute postburn edema through modulation of
      the postburn tissue pressure effects.

PMID- 9177875
TI  - Immunological responses to thermal injury.

PMID- 9177876
TI  - Evaluation of lipid peroxidation and total antioxidant status in plasma of rats
      following thermal injury.
AB  - Thermal injury initiates systemic inflammatory reactions producing burn toxins,
      an inflammatory response, oxygen radicals and finally peroxidation. The
      relationship between the amount of products of oxidative metabolism and natural
      scavengers of free radicals determines the outcome of local and distant tissue
      damage, and further organ failure in burn injury. To determine the relationship
      between the level of total natural scavengers of the body, the place of
      superoxide dismutase in this capacity, and its relation with lipid peroxidation,
      malondialdehyde, superoxide dismutase levels and total antioxidant status were
      measured in plasma. Animals were subjected to 30 per cent full thickness body
      surface area burn, and their blood was collected at 24 h postburn. Plasma
      malondialdehyde levels were significantly elevated above the level of controls (P
      < 0.02). Burn injury caused a remarkable decrease in superoxide dismutase (45 per
      cent decrease, P < 0.0001) and total antioxidant status (14 per cent decrease, P
      < 0.01) when compared to control.

PMID- 9177877
TI  - Suppressive effect of FC-43 perfluorocarbon emulsion on enhanced oxidative
      haemolysis in the early postburn phase.
AB  - The effect of FC-43 perfluorocarbon emulsion on resistance of red blood cells to
      oxidative haemolysis and lipid peroxidation was evaluated in rats (full skin
      thickness burns over 15-20 per cent of total body surface area). The content of
      erythrocyte malonyl dialdehyde (MDA), alpha-tocopherol, glutathione (reduced and
      oxidized forms) and oxidative haemolysis were measured at 24 h after burn injury.
      Four groups were employed: (1) non-burned non-treated, (2) non-burned but treated
      with FC-43 perfluorocarbon emulsion (5 ml/kg bodymass i.v.), (3) burned non
      treated, (4) burned but treated with FC-43 emulsion (5 ml/kg bodymass i.v.). The
      non-burned groups showed no significant differences in oxidative haemolysis, MDA
      levels or alpha-tocopherol and glutathione content. In the burned non-treated
      group the oxidative haemolysis elevated by 190 per cent (P < 0.001), MDA content
      increased by 43 per cent (P < 0.05), whereas the concentration of alpha
      tocopherol and reduced glutathione (GSH) decreased significantly by 36 per cent
      and 18 per cent, respectively. The results showed reduction in the postburn MDA
      content by 30 per cent (P < 0.02) and oxidative haemolysis by 44 per cent (P <
      0.001) after treatment with FC-43 emulsion. FC-43 emulsion did not change
      significantly the levels of alpha-tocopherol and GSH in erythrocytes after
      thermal injury. It is concluded that FC-43 perfluorocarbon emulsion
      administration suppresses early postburn lipid peroxidation and increases the
      resistance of red blood cells to oxidative haemolysis.

PMID- 9177878
TI  - Extracellular matrix proteins induce changes in intracellular calcium and cyclic
      AMP signalling systems in cultured human keratinocytes.
AB  - The purpose of this study was to investigate whether extracellular matrix
      proteins which influence human keratinocyte behaviour are capable of altering
      intracellular signalling systems in these cells. The effects of extracellular
      matrix proteins on two major signal transduction pathways, intracellular calcium
      and cyclic adenosine monophosphate (cyclic AMP), were investigated. The
      extracellular matrix proteins examined were the basement membrane preparation
      matrigel, collagens type I and IV, vitronectin and its active tripeptide
      component Arg-Gly-Asp (RGD). Acute additions of matrigel, vitronectin and RGD
      caused rapid transient increases in intracellular calcium and, together with
      collagen type I, also caused sustained elevations in basal calcium when cells
      were grown on these substrates. Cyclic AMP production was unaffected by acute
      exposure to these extracellular matrix proteins. Culture of cells on matrigel,
      collagen type I or IV, however, significantly reduced basal cyclic AMP
      accumulation and increased the response of the cells to the receptor-independent
      agonist forskolin. It is concluded that in vitro some extracellular matrix
      proteins can initiate both acute and sustained changes in intracellular
      signalling in human keratinocytes.

PMID- 9177879
TI  - Impaired actin polymerization and depolymerization in neutrophils from patients
      with thermal injury.
AB  - Acquired neutrophil dysfunction is considered an important cause of increased
      susceptibility to infection in patients with burns. In the early postinjury
      phase, large amounts of circulating chemo-attractants, cytokines and endotoxins
      induce strong systemic activation of neutrophils which may impair their motile
      functions. Actin is the most prevalent component of the microfilament lattice
      that generates force for the neutrophil motile responses, and in the present
      study we examined the dynamics of actin polymerization and depolymerization in
      neutrophils from 11 patients with large burns. At admission, the amount of
      polymerized actin in unstimulated neutrophils was 39.9 per cent higher than that
      of parallel controls. In addition, there was a positive correlation between the
      amount of polymerized actin and the total body surface area (TBSA) burn. The time
      course of patient neutrophil actin polymerization in response to FMLP, C5a, (Ser
      IL-8)72, (Ala-IL-8)77 and crosslinking of surface Fc gamma RII was similar to
      that of controls, and the maximal amount of neutrophil F-actin was demonstrated
      after 30 s stimulation. At the peak of actin polymerization, however, patient
      neutrophils contained 27.3, 24.0, 24.7 and 25.6 per cent more polymerized actin
      than control cells stimulated with FMLP, (Ser-IL,-8)77, (Ala-8)77 and Fc gamma
      RII crosslinking, respectively. However, the relative increase of neutrophil F
      actin following stimulation was significantly lower in patients than in controls.
      Moreover, the rate of patient neutrophil actin depolymerization was 39.0, 23.5,
      63.3 and 51.7 per cent lower than that of controls after stimulation with FMLP,
      C5a (Ser-IL-8)72 and Fc gamma RII crosslinking, respectively. At discharge, the
      dynamics of neutrophil actin polymerization and depolymerization were similar to
      that of controls. The results demonstrate that in neutrophils during the early
      postburn phase, there are increased basal levels of polymerized actin, a lower
      responsiveness to stimulation and a reduced rate of actin depolymerization. As
      periodic polymerization and depolymerization of actin is essential for all
      neutrophil motile responses, it is probable that the alterations observed may
      contribute significantly to the overall neutrophil dysfunction following thermal
      injury.

PMID- 9177880
TI  - Direct measurement of cutaneous pressures generated by pressure garments.
AB  - Pressure garments are the mainstay of burn scar management despite limited
      scientific evidence. This study demonstrates a simple method of directly
      measuring the cutaneous pressures generated by a pressure garment. The results
      show pressure garments generate an increase in subdermal pressures in the range 9
      90 mmHg depending on the anatomical site. Garments over soft sites generate
      pressures ranging from 9 to 33 mmHg. Over bony prominences the pressures range
      from 47 to 90 mmHg. This method is believed to be more representative of the
      pressures generated than the interpositional techniques that measure garment-skin
      interface pressure, as it avoids garment distortion, the interference effect of
      the measurement device (size, conformation, area) and directly measures subdermal
      pressures. The method should be useful for larger research projects on pressure
      therapy and also for clinical management of pressure garments in the treatment of
      hypertrophic scar.

PMID- 9177881
TI  - Anisodamine restores bowel circulation in burn shock.
AB  - In a group of eight burn patients with a mean of 65.3 +/- 17.4 per cent TBSA burn
      injury (range 50-90 per cent TBSA), accompanied by a mean of 43.5 +/- 18.9 per
      cent TBSA full-thickness injury, it was shown that the evidence of global
      hypovolaemia had disappeared at 12 h after the injury following aggressive fluid
      resuscitation, while there was still a subnormal pHi of stomach at 48 h. As a
      prolonged period of inadequacy of oxygen delivery to the intestine might result
      in impairment of the intestinal mucosal barrier function, and then endogenous
      endotoxaemia might ensue, it seems to be important to correct intestinal hypoxia
      as early as possible. Since the inadequate perfusion to the gut wall is due to
      selective vasoconstriction of the mesenteric vasculature, logic dictates that the
      use of a vasodilator is in order. Anisodamine, an anticholinergic drug, was then
      given in six burn patients with comparable burn size and amount of fluid
      replenishment with the eight patients in the control group. It was clearly
      demonstrated that gastric pHi returned to normal before 48 h after injury. Plasma
      endotoxin and TNF contents were measured, and they were significantly lower than
      control values after 72 h. In conclusion, it is believed that anisodamine might
      be a valuable adjunct to the resuscitation regime of burn shock, and, therefore,
      a promising drug to abate endogenous endotoxaemia subsequent to splanchnic
      vasoconstriction due to hypovolaemia. The shortcomings of the drug were a mild
      abdominal distention and tachycardia after its administration.

PMID- 9177882
TI  - The burn specific pain anxiety scale: introduction of a reliable and valid
      measure.
AB  - The burn specific pain anxiety scale (BSPAS) is a nine-item self-report scale for
      the assessment of pain-related and anticipatory anxiety in burned patients. This
      paper describes a study designed to explore the psychometric properties of the
      scale. The study used 35 burned patients hospitalized in Rotterdam and Groningen,
      The Netherlands, to confirm the internal consistency of the instrument and
      provide an assessment of its validity. The alpha coefficient was high: 0.94. The
      BSPAS correlated statistically significantly with the STAI-S, procedural pain,
      non-procedural pain, and nurses' visual analog observation ratings of tension.

PMID- 9177883
TI  - Shack fires: a consequence of urban migration.
AB  - Shack fire burns are the second most common reason for admission of patients to
      the burns unit in Cape Town. A retrospective analysis of 99 patients between
      January 1993 and June 1995 was undertaken to investigate the demographics and
      mortality associated with shack fire burns. There were 58 males and 41 females
      with an average age of 34 years (range 13-17 years). The average total burn
      surface area (TBSA) was 31 per cent (range 3-98 per cent) and in 67 of these
      patients a full-thickness component to the burn was noted. The upper limbs and
      head and neck were the most commonly burnt areas. Inhalation injury affected 61
      patients, 18 of whom required admission to an intensive care unit for assisted
      ventilation due to respiratory failure. Thirty nine patients (39.4 per cent)
      died. Shack burns are a specific entity associated with significant morbidity and
      a high mortality. The injuries had a major impact on the victim's life and
      prevention is the best form of treatment.

PMID- 9177884
TI  - Elevated compartmental pressures after closure of a forearm burn wound with a
      skin-stretching device.
AB  - A case of successful delayed primary closure of an upper extremity electrical
      blow-out injury is described using an alternative technique. The Sure-Closure
      skin-stretching device was used for permanent wound closure following serial
      debridement to protect the radial artery which was exposed over a distance of 21
      cm. This method increases the options possible to achieve wound closure. However,
      the potential risks of this method include potentially high compartment pressures
      over a prolonged time in the postoperative period which requires close monitoring
      of limb perfusion.

PMID- 9177885
TI  - Urgent delivery, the treatment of choice in term pregnant women with extended
      burn injury.
AB  - Two pregnant patients at term, suffering from major burn wounds, were treated in
      our burn unit during the year 1995, both were delivered immediately after
      admission by caesarean section. One of them had smoke inhalation injury which
      needed mechanical ventilation, both mothers and newborns survived. In spite of
      low maternal carboxyhaemoglobin the fetal cord blood carboxyhaemaglobin was high,
      supporting an objective physiological basis for the previous empirical conclusion
      of early delivery in pregnant patients at term with extensive burn injury (50 per
      cent TBSA and more). This obvious favourable outcome highlights the importance of
      urgent delivery in term pregnant women suffering a major burn injury.

PMID- 9177886
TI  - Continuous haemofiltration and haemodiafiltration for acute renal failure in
      severely burned patients.
AB  - Among 970 burned patients admitted between April 1987 and September 1994, 16 (1.6
      per cent) presented acute renal failure requiring dialytic support and were
      treated by continuous renal replacement therapy as first-line modality. Their
      mean burned surface area was 58.0 +/- 5.7 per cent. Acute renal failure mainly
      occurred in the second week following admission in relation to sepsis and
      nephrotoxic drugs. Four types of continuous renal replacement therapy were
      performed: continuous arteriovenous haemofiltration and haemodiafiltration (CAVH
      and CAVHDF) and continuous venovenous haemofiltration and haemodiafiltration
      (CVVH and CVVHDF). Compared to 33 critically ill patients without burns also
      treated for acute renal failure by continuous haemofiltration or
      haemodiafiltration during the same period, the mean duration of therapy was
      longer for the burned patients (24.2 +/- 9.4 vs. 5.3 +/- 0.8 days). Although mean
      urine outputs and ultrafiltration rates were similar for both groups, fluid
      administration was higher for burned patients (8.2 +/- 0.7 vs. 3.3 +/- 0.2
      l/day). Total weight loss during therapy was significantly greater in burned
      patients (12.6 +/- 3.6 vs. 6.8 +/- 1.0 kg), in relation to longer treatment
      period. Bleeding complications were more frequent in burned patients (56 vs. 15
      per cent). Mortality rates were similar in both groups (82 vs. 82 per cent). In
      conclusion, when aggressive initial fluid resuscitation is applied following burn
      injury, the occurrence of acute renal failure is low, delayed and multifactorial.
      Since they are haemodynamically well tolerated and provide a good metabolic and
      volaemic control, continuous renal replacement therapies appear to be useful
      modalities for burned patients with acute renal failure. However, as bleeding
      complications are more frequent, careful monitoring is necessary.

PMID- 9177887
TI  - Controlled mechanical hypoventilation in a paediatric burn patient as treatment
      of acute respiratory distress syndrome.
AB  - The paediatric patient we are describing suffered a scald injury covering 83 per
      cent of the total body surface area (TBSA). This injury was complicated by
      Klebsiella pneumoniae septicaemia resulting in multiorgan failure (MOF). Acute
      respiratory distress syndrome (ARDS), gastrointestinal insufficiency,
      hepathopathy and wound conversion to full thickness posed the main problems. The
      boy was ventilated with pressure-controlled mechanical ventilation. The concept
      of permissive hypercapnia (PHC) resulted in a complete resolution of ARDS within
      4 weeks. From our experience, further lung injury among infants and children
      suffering from severe ARDS can be avoided by using controlled mechanical
      hypoventilation. It is a simple and safe technique that allows adequate
      oxygenation.

PMID- 9177888
TI  - An extraordinary cause of scalding injury in childhood.
AB  - In an attempt to statistically evaluate burn injuries in childhood in terms of
      incidence, aetiology, mortality and morbidity, a surprising aetiological cause
      was noticed, not only as having a high mortality rate, but also as being
      preventable in most cases if simple precautions are taken. Fifteen preschool
      children had been severely scalded in kitchens by hot milk which was heated in a
      cauldron to produce cheese, a traditional custom. The clinical data relating to
      this aetiology and the probable underlying factors pertaining to the social
      characteristics are given and discussed.

PMID- 9177889
TI  - A thermal burn to a prolapsed uterus.
AB  - Burns to the concealed area of the perineum, are relatively rare and usually
      associated with massive burns and a high mortality rate. A rare case of a thermal
      burn to a prolapsed uterus is described. The victim was a 72-year-old Bedouin
      woman, with a 70 per cent total body surface area deep burn from an open fire. In
      addition to the conventional treatment dictated by such a burn, two unique
      problems must be considered: (1) the common pathogens of the uterus, Neisseria
      gonorrhoeae, Chlamydia trachomatis and mycoplasma, are different from those of
      the skin; (2) the lymphatics of the uterus drain directly into the abdominal
      cavity and the risk of peritonitis and generalized infection is potentially
      higher. Intravenous, prophylactic, broad-spectrum antibiotics were therefore
      initiated immediately following admission. These included: cefoxitin, gentamicin
      and metronidazole a combination that covers both the potential pathogens of the
      uterus and the common pathogens of the skin. In addition, and for the same
      reason, Betadine substituted Flamazine for the local treatment of the exposed
      uterus. Our patient did not survive the burn, but in a similar, unusual case, the
      local and systematic remedies must protect against uterine pathogens that are not
      commonly seen in a burn victim.

PMID- 9177890
TI  - Combined thermal and crush injury to the hand and fingers.
AB  - Combined thermal and crush injury is a relatively rare type of injury, although
      it may be more common in industrial settings. The combined insult of heat and
      pressure results in an injury that apparently is more severe than the simple
      additive effect, as the heat is transmitted deeper through the crushed tissues.
      The full extent of tissue destruction cannot always be fully recognized
      initially. Treatment in stages is the preferred approach, rather than attempted
      immediate reconstruction procedures. Failure of immediate skin grafting
      procedures in some of the cases presented herein was the result of
      underestimation of the severity of trauma. Early debridement should be done soon
      after admission. Definitive treatment as dictated by the magnitude of injury
      needs to be delayed until the extent of injury is delineated. Our conclusions
      from the presented experience with this type of injury were successfully applied
      in the treatment of the last presented patient.

PMID- 9177892
TI  - About changing faces: promoting a good quality of life for people with visible
      disfigurements.

PMID- 9177891
TI  - Phenolic household disinfectants--further precautions required.
AB  - Phenolic disinfectants (e.g. Meytol, Dettol, etc.) are widely used for domestic
      purposes. Instructions on the bottles are clearly given with regards to the
      dilutions that should be used. In domestic cleaning, these instructions are often
      ignored and higher concentrations are used with the thinking that 'the more I
      pour, the cleaner it gets!'. Furthermore, cleaning equipment is sometimes stored
      without prior rinsing with fresh water. As water evaporates much faster than
      phenol, the solution on stored mops/ brushes, etc. becomes progressively more and
      more concentrated and can cause chemical burns when these utensils are handled at
      a later time. We therefore suggest that two further instructions should be added
      to the usual instructions on bottles of household phenolic disinfectants, namely:
      'wear gloves when performing domestic cleaning' and 'wash all cleaning equipment
      with plenty of fresh water after use'. We support this by a case report of a 65
      year-old man who sustained full-thickness, painless chemical burns to his right
      hand after handling a moist mop which had been used for cleaning a carpet with a
      phenolic household disinfectant solution 2 days earlier.

PMID- 9177893
TI  - Autotransfusion techniques in burn surgery.

PMID- 9177895
TI  - A study of self-monitoring processes and coping behaviour in burns victims.
AB  - This is a quasi-experimental study to examine the manner in which burns victims
      cope with and self-monitor their presentation. Self-monitoring was measured by
      the Revised Self-monitoring Scale and coping with the Revised Ways of Coping
      Scale. Observations were made at weeks 2, 8 and 16 postburn. Conclusions were
      that self-monitoring does not change over time and the location of burns scars
      does not affect coping or self-monitoring. At 8 weeks postburn females have
      encountered more stresses and do more coping than males, and females use more
      emotion-focused coping than males as a whole. Recommendations are for increased
      patient education programmes on postburn information and predischarge counselling
      and for more staff education programmes on identification of major coping
      strategies and predischarge planning.

PMID- 9177894
TI  - Action of trypsin:chymotrypsin (Chymoral forte DS) preparation on acute-phase
      proteins following burn injury in humans.
AB  - A study was carried out to investigate the efficacy of trypsin: chymotrypsin
      (Chymoral forte DS) preparation on burn patients by analysing the changes taking
      place in serum acute-phase proteins. Serum proteins were analysed qualitatively
      and quantitatively for both control and enzyme-treated groups by the methods of
      Western Blot, ELISA and Turbidimetric assays. Furthermore, the trypsin inhibitory
      capacity (TIC) of the sera was also determined. Significant differences were
      observed between a control group of patients and a parallel group treated with
      trypsin: chymotrypsin preparation. During the first phase of burn wounds an
      initial rise was seen in C-reactive protein, alpha 1-antitrypsin, alpha 2
      macroglobulin and TIC in both the groups. In the following days, enzyme
      preparation inhibited the rise in C-reactive protein titres and enhanced the rise
      in alpha 1-antitrypsin, alpha 2-macroglobulin and TIC. The above studies clearly
      indicate that the changes in serum acute-phase proteins between the control and
      treated groups reflect the anti-inflammatory activity and hence the therapeutic
      efficacy of Chymoral forte DS.

PMID- 9177896
TI  - The cutometer and ultrasonography in the assessment of postburn hypertrophic scar
      -a preliminary study.
AB  - Sixteen patients with various degrees of postburn hypertrophic scars were
      evaluated by ultrasonography and elastometry. An Aloka Echo Camera (SSD-500) with
      a 7.5 MHz probe and a Cutometer SEM 575 skin elastometer were used. Serial
      monthly examinations were performed using both pieces of equipment. In some
      patients, more than one scar was assessed. The assessments were correlated with
      clinical grading of the progress of the scars. It was noted that ultrasonography
      was very sensitive in the localization of scar tissues, distinguishing them from
      normal skin, assessment of thickness and also delineation of the extent of scar
      tissues. The subcutaneous part of the scar could be assessed. Cutometer SEM 575
      is a new machine that applies a gentle suction to the skin to measure its
      viscoelasticity. It is sensitive, the inter-observer variation is low, and it
      could be used for the grading of a scar. These two assessment techniques
      compliment other methods of scar assessment and will prove useful when assessment
      of response to treatment is required.

PMID- 9177897
TI  - Advances in the treatment of burn patients.

PMID- 9177898
TI  - Delivery of medication by iontophoresis to treat post-burn hypertrophic scars:
      investigation of a new electronic technique.
AB  - At present, direct current (DC) and pulsed direct current (PDC) methods are used
      for iontophoresis. Although the DC field has high efficiency, it exhibits some
      side-effects. The PDC field has little side-effects, but the efficiency is lower.
      In this study, a new iontophoretic drug device was designed for providing the
      maximal efficiency with the minimal side-effects. Tests of animal and human
      models showed that the permeation rate of the new field was higher than that of
      PDC and DC fields, and side-effects were lower than that of the DC field.

PMID- 9177899
TI  - Evaluation of artificial skin (Integra) in a rodent model.
AB  - The biocompatibility of artificial skin (Integra) has been investigated in clean
      surgical wounds of 20 guinea-pigs. A rectangular 3 x 3 cm full-thickness skin
      defect with excision carried down to the panniculus carnosus was prepared on the
      dorsal area of the guinea-pig. A thin layer of silver sulfadiazine cream was
      applied and artificial skin was placed to cover the wound. At day 14, the
      uppermost silicone layer was removed. Good take of the artificial skin was
      observed in 18 of 20 animals. Microscopy showed good vascular ingrowth in 14 of
      the 18 animals. The remaining four animals showed necrotic tissue, absence of
      vascularization and haemorrhage in the wound bed. Two of the 20 wounds showed
      purulent discharge. In this animal model, clinical 'take' of the neodermis was
      achieved in 18/20 animals (90 per cent), while vascular ingrowth was observed in
      only 14/20 animals (70 per cent). These results suggested that artificial skin in
      clean surgical wound is readily biologically incorporated into surrounding viable
      tissue.

PMID- 9177900
TI  - Management of partial-thickness burn wounds by amniotic membrane: a cost
      effective treatment in developing countries.
AB  - Burns incidence in our country has been on the increase over the past two
      decades. Cost-effective management of burn wounds has become the prerogative as
      our annual budget for burn care is limited. We have used human amniotic membrane
      procured from HbSAg, HIV-seronegative mothers undergoing caesarean section as a
      temporary biological dressing on superficial and deep partial-thickness burns.
      The advantages of amniotic membrane cover are reduction in pain, early drying of
      the wound and epithelialization. This type of wound management has been used in
      350 cases. It has reduced the number of days stay in hospital and the bulky
      dressings that are conventional. Considering the patient acceptability, reduced
      hospital stay and reduction in cost, we find that treatment of superficial and
      deep partial-thickness burns with amniotic membrane is ideal for a developing
      country.

PMID- 9177901
TI  - Requirement for Rho in integrin signalling.
AB  - Overnight culture of Swiss 3T3 cells in serum-free medium leads to loss of focal
      adhesions and associated actin stress fibres, although the cells remain well
      spread. The small GTP-binding protein Rho is required for the formation of stress
      fibres and focal adhesions induced by growth factors such as lysophosphatidic
      acid (LPA) in serum-starved Swiss 3T3 cells, and for the LPA-induced tyrosine
      phosphorylation of several focal adhesion proteins. Plating of cells on
      extracellular matrix proteins also stimulates protein tyrosine phosphorylation
      and the formation of stress fibres and focal adhesions in the absence of added
      growth factors. These responses were inhibited in cells scrape-loaded with the
      Rho inhibitor C3 transferase. Focal adhesion and stress fibre formation was also
      triggered by addition of a peptide GRGDS, which is recognised by a number of
      integrins and is contained within the cell binding domain of a variety of
      extracellular matrix proteins. The activity of the GRGDS peptide was blocked by
      microinjecting cells with C3 transferase, suggesting that peptide binding to
      integrins stimulates a Rho-dependent assembly of focal adhesions. These
      experiments indicate that Rho is involved in signalling downstream of integrins.

PMID- 9177902
TI  - N-cadherin promotes adhesion between invasive breast cancer cells and the stroma.
AB  - Calcium-dependent cell adhesion molecules (cadherins) are involved in maintaining
      the epithelial structure of a number of tissues including the mammary gland. In
      breast and other tumor types, loss of E-cadherin expression has been seen in high
      grade tumors and correlates with increased invasiveness. Here we show high levels
      of expression of N-cadherin in the most invasive breast cancer cell lines which
      was inversely correlated with their expression of E-cadherin. A stromal cell line
      also expressed N-cadherin in accordance with its fibroblastic morphology. N
      cadherin localized to areas of cell-cell contact in all cells that expressed it.
      Calcium-dependent intercellular adhesion of N-cadherin-expressing breast cancer
      and stromal cells was specifically inhibited by an anti N-cadherin monoclonal
      antibody. In addition, N-cadherin promoted the interaction of invasive breast
      cancer cells with mammary stromal cells; in contrast, E-cadherin expressing cell
      lines did not co-aggregate with stromal cells. The combined results suggest a
      functional role for N-cadherin in cohesion of breast tumor cells which, in
      addition promotes their interaction with the surrounding stromal cells, thereby
      facilitating invasion and metastasis.

PMID- 9177904
TI  - E-cadherin engagement stimulates tyrosine phosphorylation.
AB  - Cadherins are cell adhesion molecules concentrated at intercellular adherens
      junctions, where they form a multiprotein complex with cytoplasmic catenins.
      Although cell-cell interactions affect many aspects of cell behavior, little is
      known about signaling pathways triggered by cadherin engagement. We show here
      that E-cadherin-mediated cell-cell adhesion leads to a rapid increase in tyrosine
      phosphorylation at sites of cell-cell contact and that this stimulation of
      tyrosine phosphorylation can be mimicked by aggregation of E-cadherin with
      antibodies. The proteins that become phosphorylated are distinct from those
      previously shown to be tyrosine phosphorylated in response to integrin-mediated
      adhesion and include ras-GAP. We also find that E-cadherin-mediated tyrosine
      phosphorylation is not required for the assembly of adherens-type junctions.

PMID- 9177903
TI  - Coordinated regulation of fibronectin fibril assembly and actin stress fiber
      formation.
AB  - Assembly of a fibronectin (FN) matrix is a multistep process which influences a
      number of cellular functions including intracellular cytoskeletal organization
      and signaling responses. We have previously reported on a recombinant FN (recFN),
      FN delta III1-7, which differs from native FN in its rate of fibril formation. To
      determine the intracellular consequences of a delay in assembly, we compared the
      distribution of cytoskeletal proteins during the formation of native and recFN
      matrices by immunofluorescence at various time points. CHO alpha 5 cell
      cytoskeleton was reorganized in response to both native and recFN matrix
      formation. Assembly of native FN induced a rapid reorganization of actin into
      stress fibers and colocalization of alpha 5 beta 1 integrin, focal adhesion
      kinase (FAK), vinculin, and paxillin to regions of cell-matrix contact. alpha 5
      beta 1 integrins and FAK are also clustered upon binding of FN delta III1-7 to
      cells but actin reorganization and focal adhesion formation are delayed and
      appear to be dependent on the formation of FN delta III1-7 fibrils. These results
      suggest that the structural framework of the matrix plays an important role in
      the ability of FN to initiate intracellular responses.

PMID- 9177905
TI  - Role of integrins and evidence for two distinct mechanisms mediating human
      colorectal carcinoma cell interaction with peritoneal mesothelial cells and
      extracellular matrix.
AB  - Peritoneal carcinomatosis involves a series of events including tumor cell
      interactions with mesothelial cells and the extracellular matrix (ECM). We have
      studied the adhesive and invasive properties of four human colorectal carcinoma
      cell lines (Co115, HT29, SW480, SW620) confronted in vitro with a human
      mesothelial cell monolayer or with the ECM proteins collagen IV, laminin-1,
      fibronectin, tenascin-C and vitronectin. Quantitation was achieved following
      staining of tumor cells with the calcein-AM fluorescent dye. We found that all
      four cell lines rapidly adhered to a mesothelial cell monolayer. This adhesion
      event was not inhibitable by anti-integrin and anti-CD44 antibodies. Following
      initial attachment, the SW480 and SW620 cells invaded the mesothelial cell
      monolayer more aggressively than HT29 and Co115 cells. All cell lines adhered to
      ECM proteins with each one exhibiting an individual adhesion pattern. Adhesion to
      matrix was completely integrin-dependent. When tested in an invasion assay, HT29
      and Co115 cells crossed Matrigel-coated filters while SW480 and SW620 cells did
      not. This invasion was inhibited by anti-beta 1 integrin antibodies. Taken
      together, our results demonstrate that the initial colorectal tumor cell
      mesothelial cell interaction occurs through an integrin-independent mechanism
      while adhesion to matrix proteins and invasion through Matrigel are integrin
      dependent events. Furthermore, the different invasive capacity of SW480 and SW620
      versus HT29 and Co115 cells upon interaction with a mesothelial cell monolayer or
      Matrigel suggests that these two invasion events may be mediated by distinct
      mechanisms.

PMID- 9177906
TI  - Preferential localization of tyrosine-phosphorylated paxillin in focal adhesions.
AB  - Focal adhesions are sites for integrin-mediated attachment of cultured cells to
      the extracellular matrix. Localization studies have shown that focal adhesions
      can be stained by antiphosphotyrosine antibodies, but the role of tyrosine
      phosphorylated proteins in focal adhesions is not known. By using ventral plasma
      membranes prepared from chicken embryo fibroblasts spread on the substrate, we
      present evidence for the preferential localization of a minor pool of tyrosine
      phosphorylated paxillin in focal adhesions. Ventral plasma membranes showed an
      enrichment in beta 1-integrins, and in several tyrosine-phosphorylated
      polypeptides, while focal adhesion proteins like vinculin and paxillin, although
      localized to focal adhesions in ventral plasma membranes, were not particularly
      enriched in these preparations compared to whole cell lysates. Biochemical and
      morphological analysis of ventral plasma membranes showed a dramatic increase in
      the level of tyrosine-phosphorylation of the pool of paxillin localized to the
      adhesive sites, when compared to the paxillin present in whole cell lysates. The
      observed preferential localization of tyrosine-phosphorylated paxillin to focal
      adhesions may represent a general mechanism to compartmentalize focal adhesion
      components from large non-phosphorylated, cytosolic pools.

PMID- 9177907
TI  - Linking analytic performance goals to medical outcome.
AB  - As laboratorians relate analytic performance to medical goals, they face complex
      choices among competing subjective and objective criteria for the assessment of
      acceptable analytic error. Defining desirable performance as some fraction of
      physiologic variability provides potentially excessive benchmarks for quality.
      More important than the recognition of health are the clinical decisions which
      deal with diseases, particularly the latters' degrees of severity and the
      different medical actions these prompt. It is equally essential to take into
      account the reasoning by which physicians arrive at these decisions, since their
      mental processes condition desirable performance goals. Considering these
      modalities, a universal model of analytic performance requirements uniformly
      applicable to all measured parameters clearly cannot be devised. Rather,
      tolerance limits for analytic error must be tailored to specific medical
      problems. To facilitate this seemingly Herculean task, this paper develops
      concepts and principles derived from operation research, and illustrates their
      application by three examples. The generic conclusion evidenced by the latter is
      that the linkage between analytic performance goals and medical strategies is
      reciprocal, namely that outcome can just as well be optimized by tailoring
      medical strategy to existing analytic performance as by adapting analytic
      performance to medical strategy.

PMID- 9177908
TI  - The complex connections between test properties and relevant outcomes: widening
      the perspective.
AB  - The formulation of analytical goals for the clinical laboratory should be based
      upon a wide perspective embracing multiple viewpoints. Mathematical consideration
      of analytical error is necessary but insufficient to address societal forces
      demanding increased effectiveness while also reducing costs. Appropriate goals
      also require the study of cognitive science, health policy research, and the
      measurement of subjective preferences and of predictive probability. Overall
      goals must focus on health outcomes that emphasize prevention or postponement of
      morbidity and the need for acute care. Care process variables that influence
      health outcomes must be identified. Process improvement through reduction in
      process variation can then improve health outcomes. Important process variables
      will be identified in the cognitive process as well as in the pre- and post
      analytical phases of laboratory care. The impact of test characteristics upon the
      laboratory's contribution to health goals are exemplified by monitoring of oral
      anticoagulant, thyroxine, aminoglycoside and intensive insulin therapy plus
      identification of clinically occult diseases such as hypothyroidism and
      hemochromatosis.

PMID- 9177909
TI  - Diagnostic validity as a theoretical concept and as a measurable quantity.
AB  - The analytical result of a laboratory examination is a scientific fact and has no
      medical meaning as such. It must be interpreted to become a medical finding. To
      explain the very complex cognitive procedure of the interpretation a three-level
      model is used. In an environment of cost containment in health care systems the
      quality of medical laboratory findings is very important. Analytical results are
      monitored by quality control procedures. For measuring the performance of medical
      findings the concept of the 'validity' of a laboratory test is used. Validity
      means the 'degree of achieving the objective'. Accordingly, a valid laboratory
      finding is one which correctly answers the question which the physician at the
      sick-bed directs to the laboratory. Quantitative measures for the validity of
      interpretation can be developed by an analysis of the underlying classification
      processes. Characteristic indices describing the validity quantitatively in terms
      of conditional probabilities can be derived from decision tables. Examples of
      'validity indices' are diagnostic (or prognostic) 'sensitivity' and
      'specificity'. These indices are powerful tools for developing strategies for the
      clinical use of laboratory examinations in diagnosis, prognosis and therapy
      management. Moreover, validity indices are appropriate output quantities for the
      estimation of effectiveness and efficiency of a diagnostic or prognostic
      examination.

PMID- 9177910
TI  - The evolution and limitations of accuracy and precision standards.
AB  - Limits of maximum allowable analytical imprecision have been defined on the basis
      of normal range (Tonks), composite biological variation (Cotlove),
      intraindividual biological variation (Aspen Conference, College of American
      Pathologists), medical significance (Barnett, Skendzel), and a combination of
      medical significance and biological variation (Fritsche. Klee). Because error
      limits based on medical significance are less stringent than those based on
      biological variation, performance goals based on medical significance are more
      likely to be attained by laboratories than those defined by biological variation.
      Most clinical scientists realize that the goal to limit the analytical C.V. to
      one-half or less of the biological C.V. is arbitrary, and for the large majority
      of laboratory tests of no benefit to the patient, for the major component of
      total variation is not the analytical imprecision, but the intraindividual
      variation itself. Furthermore, the purpose of laboratory testing is to help
      physicians confirm or exclude potential diagnoses and monitoring therapy rather
      than detecting small deviations from normal values. Small changes in test values
      are quite often uninterpretable or lead to costly albeit fruitless
      investigations. In view of diminishing resources for health care we must
      establish the accuracy and precision required for each test. While improving the
      accuracy of some tests would be desirable, for most of them further improvement
      would be irrelevant to patient care because few tests are pathognomonic by
      themselves and quite often diagnosis is not made on the basis of a single
      laboratory result. If more accuracy is desirable, it must also be affordable and
      benefits should outweigh costs.

PMID- 9177911
TI  - Clinical laboratory quality control: a costly process now out of control.
AB  - We studied laboratory internal quality control (QC) processes using the College
      of American Pathologists Q-Probes program. Over 500 institutions participated,
      providing practices based on approximately 710,000 cholesterol, 880,000 calcium,
      400,000 digoxin, and 1,180,000 hemoglobin QC results. The costs of QC included
      participant median control samples rates comprising 9.1, 9.4, 37.0, and 6.8% for
      the four analytes respectively, repeat patient test rates of 0.36% for hemoglobin
      to 0.65% for digoxin, and median delays in reporting results when QC exceptions
      occurred of 15.8 min for calcium to 24.7 min for hemoglobin. Quality control
      practices were complex and highly variable among participants and frequently
      differed from internal laboratory protocols and from long-established quality
      guidelines. We conclude that QC is costly, and laboratorians frequently do not
      follow established QC practices, in part because they are complex. To improve
      compliance, we believe QC practices must be simplified.

PMID- 9177912
TI  - A conceptual model for establishing tolerance limits for analytic bias and
      imprecision based on variations in population test distributions.
AB  - A conceptual model is proposed for defining analytic bias limits utilizing the
      variations found in cumulative test value distributions. The model is based on
      the propositions that changes in analytic bias are more important than analytic
      imprecision in medical diagnoses and that analytic bias alters clinical
      specificity more than clinical sensitivity. The rationale for these propositions
      are presented along with a step-by-step procedure for estimating bias tolerance
      limits. These concepts are illustrated with an example using prostate-specific
      antigen. A second protocol is provided to define analytic imprecision tolerance
      limits, based on the quality control performance characteristics required to
      maintain the bias tolerance limits. This model can be applied to most chemistry,
      immunoassay, and hematologic quantitative assays. The relationship of this
      procedure to the published procedures using biologic variation for defining
      analytic tolerance limits is discussed.

PMID- 9177913
TI  - The influence of analytical bias on diagnostic misclassifications.
AB  - Quality specifications for analytical imprecision and bias based on the state of
      the art; 'biology' and 'analysis of clinical situations' have been proposed by
      several scientists. Most interesting is the assessment of 'diagnostic
      misclassifications' based on direct evaluation of the consequences of analytical
      bias on the percentage of false positives and false negatives from a clinical
      decision situation, or based on the percentage of healthy individuals outside
      each reference limit when common reference intervals are used. With use of
      graphical or computer simulations assuming increasing (positive or negative)
      analytical bias, the expected percentage of misclassifications can be estimated-
      and, for the error for which the outcome (the fraction of misclassifications) is
      considered unacceptable, the maximum allowable analytical bias can be defined. An
      overview is given of previous proposals for specification of allowable analytical
      bias, and new examples are presented: (i) for S-transferrin. an analytical bias
      of +10% will increase the percentage of healthy individuals with measured
      concentration values above the upper reference limit from 2.5 to 10% (ii) the
      percentage of healthy men with concentration values for S-cholesterol above 6.2
      mmol/l (240 mg/dl) will vary between 25 and 85% for analytical bias from - 1.0 to
      +1.0 mmol/l (+/- 16%): (iii) for glycated haemoglobin, two examples are given
      which illustrate the effect of analytical bias on the risk of retinopathy and so
      called 'microalbuminuria' for measured values identical to the target 7.5% and
      10.1% glycated haemoglobin, respectively. It is concluded that analytical bias
      may have significant impact on diagnostic performance, better standardization is
      needed, and quality specifications for allowable analytical bias should be based
      on medical usefulness criteria or, if such data are not available, on biological
      criteria.

PMID- 9177914
TI  - Assuring quality in laboratory testing at the point of care.
AB  - The science of laboratory medicine has undergone much change during recent years.
      Despite more recent emphasis on quality improvement, there has not been
      sufficient attention paid to effective quality management of new approaches to
      laboratory testing such as point of care testing. It is important that
      appropriate resources be allocated to quality management, so that waste is
      minimized and that resources which are expended may be demonstrated to affect the
      quality of patient care in a positive way. Older quality management tools such as
      process quality control and proficiency testing are vital to the success of point
      of care testing programs, however, new ways of looking at the use of these tools
      are required. Newer approaches such as electronic quality control of point of
      care devices and an expanded role of total quality management strategies will
      enhance rather than supplant the more traditional quality improvement mechanisms.

PMID- 9177915
TI  - HLA-B27, rheumatoid factor and spondyloarthritis.

PMID- 9177916
TI  - Oxidative burst of neutrophils in patients with rheumatoid arthritis: influence
      of various cytokines and medication.
AB  - OBJECTIVE: Toxic oxygen products are believed to be implicated in tissue damage
      in some complex-mediated diseases such as rheumatoid arthritis. In the present
      study we compared the superoxide (O2) production of polymorphonuclear leukocytes
      (PMNs) in 21 patients with rheumatoid arthritis (RA) with that of 9 healthy
      controls, examining the effect of different stimulants and cytokines on the
      oxidative burst (OB). Since many drugs used in the treatment of RA may alter O2
      metabolism, the effects of antirheumatic medication were also studied. METHODS:
      Generation of superoxide anions was analysed by a flow cytometric method, using
      the fluorochrome dihydro-rhodamine. As stimulants for OB, we used N-formyl
      methionyl-leucyl-phenylalanine (fMLP), which acts via a membrane receptor, and
      phorbol-myristate acetate (PMA), which acts in a membrane receptor-independent
      manner. As preactivating substances, TNF-alpha, G-CSF and GM-CSF were applied.
      RESULTS: In RA patients under treatment with antirheumatic medication, fMLP
      induced OB (+/- cytokines) was significantly reduced, while O2 production after
      stimulation with PMA was similar compared to controls. GM-CSF showed the highest
      level of preactivation in controls, whereas in RA patients TNF-alpha proved to be
      most potent. In both controls and RA patients, a combination of GM-CSF or G-CSF
      with TNF-alpha further enhanced OB. No correlation between OB and clinical data
      or treatment could be established in RA patients. CONCLUSIONS: There is a reduced
      cytokine priming capacity for OB in RA patients under antirheumatic medication in
      spite of the presence of an intact enzyme system of OB. Antirheumatic medication
      combining multiple drugs capable of decreasing OB might effectively modulate
      oxidative metabolism.

PMID- 9177917
TI  - Provocation of hypotension and pain during upright tilt table testing in adults
      with fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia is a common but poorly understood problem characterized
      by widespread pain and chronic fatigue. Because chronic fatigue has been
      associated with neurally mediated hypotension, we examined the prevalence of
      abnormal responses to upright tilt table testing in 20 patients with fibromyalgia
      and 20 healthy controls. METHODS: Each subject completed a symptom questionnaire
      and underwent a three stage upright tilt table test (stage 1:45 minutes at 70
      degrees tilt; stage 2, 15 minutes at 70 degrees tilt with isoproterenol 1-2
      micrograms/min; stage 3, 10 minutes at 70 degrees tilt with isoproterenol 3-4
      micrograms/min). An abnormal response to upright tilt was defined by syncope or
      presyncope in association with a drop in systolic blood pressure of at least 25
      mm Hg and no associated increase in heart rate. RESULTS: During stage 1 of
      upright tilt, 12 of 20 fibromyalgia patients (60%), but no controls had an
      abnormal drop in blood pressure (P < 0.001). Among those with fibromyalgia, all
      18 who tolerated upright tilt for more than 10 minutes reported worsening or
      provocation of their typical widespread fibromyalgia pain during stage 1. In
      contrast, controls were asymptomatic (P < 0.001). CONCLUSION: These results
      identify a strong association between fibromyalgia and neurally mediated
      hypotension. Further studies will be needed to determine whether the autonomic
      response to upright stress plays a primary role in the pathophysiology of pain
      and other symptoms in fibromyalgia.

PMID- 9177918
TI  - Integrin expression on chondrocytes: correlations with the degree of cartilage
      damage in human osteoarthritis.
AB  - OBJECTIVE: To verify the distribution of different types of beta 1 integrin on
      the plasma membrane of chondrocytes and to correlate the pattern of integrin
      expression to the severity of osteoarthritis (OA). METHODS: The articular
      cartilage of ten OA patients who had undergone surgical knee replacement for
      "genu varum" were studied. The cartilage was separated into three zones that
      macroscopically and microscopically showed a decreasing degree of anatomic
      lesions. After enzymatic digestion, the isolated chondrocytes were immediately
      challenged with monoclonal antibodies against the beta 1, alpha 1-6 and alpha v
      chains. The phenotypic study was paralleled by a cell cycle analysis performed by
      flow cytometry on chondrocytes stained with propidium iodide. RESULTS:
      Chondrocytes isolated from the articular cartilage of osteoarthritic patients
      expressed, in different percentages, all the alpha chains (alpha 1-6 and alpha v)
      of the beta 1 integrins. The alpha chain most frequently expressed was alpha 1,
      followed by alpha 3, alpha 5, alpha 2 and alpha v, with lesser amounts of alpha 4
      and alpha 6. The beta 1 chain was expressed (on average) on the 40% of the
      chondrocytes regardless of the zone they were isolated from. Differential
      phenotypic analysis of the three zones showed that beta 1 integrins correlate
      inversely with the severity of the anatomic lesions and the cycle phase of the
      chondrocytes (the G0/G1 phase prevailed in the anatomically normal cartilage of
      the least damaged zone, and the S-phase in the most damaged zone). CONCLUSIONS:
      This study provides evidence of the existence of beta 1 integrins on the surface
      of chondrocytes from human OA cartilage, all of the alpha chains being
      represented, although in different percentages. Moreover, an inverse correlation
      was demonstrated between the severity of the anatomical changes found in the
      zones and the phenotypic/metabolic changes of the cells. These results, together
      with the well known inside-out signaling function of the adhesion molecules,
      highlight the key role of matrix interactions in the pathogenesis of the anatomic
      changes in OA.

PMID- 9177919
TI  - Correlation between the appearance of gelatinases in the synovial fluid of
      patients with rheumatoid arthritis and polymorphonuclear elastase, stromelysin-1,
      and the tissue inhibitor of metalloproteinase-1.
AB  - OBJECTIVE: To clarify whether gelatinases in the synovial fluid are related to
      rheumatoid arthritis (RA). METHODS: Gelatinases in the synovial fluid of patients
      with RA were analyzed by gelatin zymography. RESULTS: We classified patients into
      3 distinct groups based on the gelatinases present. Although inactive gelatinase
      A was found in the synovial fluid of all patients with RA, the presence of
      gelatinase B varied: group I contained none, group II contained inactive
      gelatinase B, and group III contained active gelatinase B. The presence of
      gelatinase B was positively correlated with the polymorphonuclear (PMN) elastase
      content of the synovial fluid. Furthermore, the presence of activated gelatinase
      B correlated well with the stromelysin-1 content. Conversely, large amounts of
      the tissue inhibitor of metalloproteinase-1 (TIMP-1) were found in the synovial
      fluid of patients in group II. CONCLUSION: The appearance and form of gelatinase
      B may reflect the inflammatory condition of patients with RA.

PMID- 9177920
TI  - Influence of methotrexate on radiographic progression in rheumatoid arthritis: a
      sixty-month prospective study.
AB  - OBJECTIVE: To evaluate if methotrexate (MTX) can slow disease progression, as
      determined radiographically, in comparison to other disease modifying drugs in
      rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: Pairs of hand and
      wrist radiographs from 30 patients treated with MTX and 30 treated with D
      penicillamine (DP) were evaluated blindly and separately by two radiologists (A
      and B) using reference radiographs for scoring. A scale scoring similar to
      Larsen's standard radiographs with minor modifications was used. The radiographs
      studied were obtained at the beginning and 5 years after therapy in both groups.
      RESULTS: A significantly greater worsening was found in the DP-treated patients
      (p = 0.025), as compared to MTX patients. Methotrexate showed a slower rate of
      disease progression than DP. Furthermore, in the MTX group 15 patients remained
      radiographically stable, 9 worsened and 6 were healed. In contrast, in the DP
      group 22 patients remained radiographically stable, 8 worsened and none improved.
      CONCLUSIONS: The rate of radiographic progression in RA patients was lower in MTX
      treated patients compared to those treated with DP. Six patients showed
      radiological improvement after MTX treatment. Therefore, it seems that MTX could
      be considered a disease modifying drug.

PMID- 9177921
TI  - Macrophage targeting with 99mTc-labelled J001 for scintigraphy of joint
      inflammation in ovalbumin-induced arthritis in rabbits.
AB  - BACKGROUND AND OBJECTIVE: J001 scintigraphy is a new approach, based on
      macrophage targeting, developed for tumor and inflammation imaging. J001, a non
      pyrogenic acylated poly(1,3)galactoside purified from the membrane of a non
      encapsulated strain of Klebsiella pneumoniae associates selectively with
      macrophages via binding to CD11b and CD14 molecules. Since macrophages play a
      primary role in inflammatory arthritis processes, J001 labeled with 99mTc
      appeared to be of interest for the scintigraphic imaging of inflammatory lesions.
      The purpose of this study was to assess the potential of J001 scintigraphy for
      imaging inflammatory arthritis in the model of ovalbumin-induced arthritis in
      rabbits. MATERIAL AND METHODS: Ovalbumin-induced arthritis was developed in 17
      rabbits. 99mTc-J001 scintigraphy was performed 4 weeks after arthritis induction
      in 17 rabbits and was repeated at 6 and 8 weeks in 8 rabbits. 99mTc-J001 and
      99mTc-MDP scintigraphy were performed before and 2.5 months after radionuclide
      synovectomy with the intra-articular injection of a high energy beta-emitting
      radionuclide (186Re) in 3 rabbits and 186Re (first subjected to a complete
      decrease of radioactivity) in 3 rabbits. RESULTS: 99mTc-J001 scintigraphy was
      able to image inflammatory arthritis 4 weeks after induction. J001 scintigraphy
      demonstrated an increased uptake earlier than MDP, which was maintained at week
      8. After radionuclide synovectomy, a clear decrease in the J001 scintigraphy
      ratio occurred, whereas the MDP scintigraphy ratio was stable. After the intra
      articular injection of inactive 186Re, no changes in MDP and J001 scintigraphy
      ratio appeared. CONCLUSION: 99mTc-J001 scintigraphy is able to image joint
      inflammation and to assess the response to anti-inflammatory treatment in an
      experimental model of arthritis.

PMID- 9177922
TI  - Immunosuppressive therapy in lupus nephritis.
AB  - OBJECTIVE: To evaluate the outcomes and side effects of immunosuppressive therapy
      in patients with lupus nephritis. PATIENTS AND METHODS: Thirty-nine patients with
      lupus nephritis assessed between 1988 and 1993 with a median follow-up of 46
      months (range 12-60 months) were studied. Lupus nephritis was biopsy-proven in 37
      patients. Patients received a median of 3 (500 mg) weekly pulses of intravenous
      cyclophosphamide followed either by azathioprine (n = 32) or oral
      cyclophosphamide (n = 7). All patients received oral prednisolone. The time from
      biopsy to renal insufficiency, defined by doubled serum creatinine and/or end
      stage renal failure, was used to assess outcome. RESULTS: There were significant
      improvements in the median changes of all major laboratory parameters. Serum
      creatinine levels did not change significantly. The prednisolone dose was
      significantly reduced during the follow-up period. OUTCOME: renal function
      remained stable in 26 (67%) and deteriorated despite therapy in 13 (33%)
      patients. 6/13 (42%) of these patients had impaired renal function at the time of
      biopsy. The adverse effects of intravenous cyclophosphamide seen were Herpes
      zoster (1), transient leucopenia (2), rash (1) and fatal septicaemia (1); of
      azathioprine urinary infections (3), leucopenia (5), rash (1) and increased liver
      enzymes (1); and of oral cyclophosphamide ovarian failure (4), Herpes zoster (3),
      haemorrhagic cystitis (1), and fatal septicaemia (1). CONCLUSIONS: Therapy with
      weekly low dose intravenous pulse cyclophosphamide to induce remission, followed
      by azathioprine appears to be useful in preserving renal function in patients
      with diffuse proliferative lupus nephritis. In comparison to other studies, the
      reduced incidence of ovarian failure using this regimen was striking.

PMID- 9177923
TI  - Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment
      of skin involvement in systemic sclerosis (scleroderma).
AB  - BACKGROUND AND OBJECTIVES: Systemic sclerosis (SSc) is a connective tissue
      disease characterized by microvascular changes and fibrosis of the skin and
      internal organs. Increased skin thickness proximal to the metacarpophalangeal
      joints is the single major diagnostic criterion. The aim of this study was to
      evaluate high frequency (20 MHz) ultrasound for the assessment of skin thickness
      in patients with SSc of different disease durations. METHODS: Skin thickness was
      measured with high frequency (20 MHz) ultrasound equipment (Dermascan) in 41
      patients with SSc (23 women and 18 men) and in 41 controls. Twenty-five patients
      had limited cutaneous systemic sclerosis (ISSc), 12 had diffuse cutaneous
      systemic sclerosis (dSSc) and 4 had suspected SSc. RESULTS: Skin thickness of the
      forearm was inversely correlated to disease duration. Compared to controls, skin
      thickness was increased over the proximal phalanx of the right second finger and
      over the forearm in patients with a disease duration of 2 years or less.
      Assessments of skin thickness in 10 controls by 2 independent investigators
      showed an inter-observer variability of 1.0% for the proximal phalanx and 0.0016%
      for the forearm. Patients whose ultrasound showed increased skin thickness on the
      hand and forearm also had thickened skin by palpation. CONCLUSION: High frequency
      (20MHz) ultrasound is a feasible method for measuring skin thickness in SSc, and
      may be useful for diagnosis, long-term follow-up, and assessment in therapeutic
      studies.

PMID- 9177924
TI  - Does serum rheumatoid factor have an influence on the clinical picture of
      ankylosing spondylitis?
AB  - OBJECTIVE: To describe the influence of serum rheumatoid factor (RF) on the
      clinical and radiological picture of definite ankylosing spondylitis (AS).
      METHODS: In a retrospective chart review of 281 AS patients typed for RF, the
      clinical picture of RF positive patients (Group 1) was compared with RF negative
      patients (Group 2); mode of onset, disease duration, and treatment were recorded.
      All patients were examined to determine their clinical status; the blood cell
      count. HLA-B27, serum IgG, IgM, IgA, and erythrocyte sedimentation rate (ESR)
      were determined, and radiological studies of the entire spine, pelvis and
      affected peripheral joints were carried out. In patients from Group 1 the HLA-DR
      was also determined. RESULTS: Fifteen of 281 patients (8 men, 7 women) with AS
      were RF+ (1:64 to 1:1024) (5.3%) and 11 were HLA-B27+. Seven patients in Group 1
      had spine involvement and chronic arthritis of the knees. Four out of these 7
      were tested for DR, and none was positive; in 6, AS and rheumatoid arthritis (RA)
      coexisted, 2 were DR1 and 2 were DR4 (test not carried out in 2). In two others
      we found spinal involvement only, and one of them had both DR1 and DR4. The onset
      of AS was similar in both groups. Group 1 was characterized by a chronic disease
      of moderate intensity with chronic arthritis of the metacarpophalangeal and
      proximal interphalangeal joints (p = 0.0008 and p = 0.04, respectively), no
      valvulopathy (p = 0.04) and fewer uveitis sequelae (p = 0.007) than Group 2. The
      ESR (p = 0.01), IgG (p = 0.008) and IgM (p = 0.0001) were higher in Group 1 than
      in Group 2. CONCLUSIONS: The presence of RF in AS is associated with a chronic
      disease of moderate intensity with chronic peripheral arthritis and fewer extra
      articular manifestations. The presence of RF, not always associated with HLA-DR,
      seems to affect the course of AS and does not necessarily indicate an association
      with RA.

PMID- 9177925
TI  - Autoantibodies to collagens in Japanese patients with ankylosing spondylitis.
AB  - OBJECTIVE: We measured antibody levels against human type I, II, III and IV
      collagens in Japanese patients with ankylosing spondylitis (AS) by enzyme linked
      immunosorbent assay (ELISA). RESULTS: Significant elevations of antibodies
      against type II (IgG and IgA classes) and type IV (IgA class) collagens were
      observed in AS patients, whilst there was no significant elevation of any
      antibody class against type I or III collagen when compared to controls.
      CONCLUSION: These findings indicate that AS patients have immune responses to
      type II and IV collagens, which may be responsible for sustaining the
      characteristic local inflammations in AS.

PMID- 9177926
TI  - Antibodies against Chlamydia pneumoniae, cytomegalovirus, enteroviruses and
      respiratory syncytial virus in patients with polymyalgia rheumatica.
AB  - OBJECTIVES: To investigate the association between the onset of polymyalgia
      rheumatica (PMR) and prior or persistent infection with Chlamydia pneumoniae or
      cytomegalovirus (CMV) (both known to infect the vessel wall) enteroviruses (EV)
      or respiratory syncytial virus (RSV). METHODS: Serum samples were collected from
      48 patients with newly-diagnosed PMR and from 22 controls of the same age. The
      presence of IgG, IgA and IgM antibodies to C. pneumoniae, IgG and IgM antibodies
      to CMV and EV, and complement fixing antibodies to RSV were analysed. RESULTS:
      Clinical symptoms of infection preceding PMR symptoms were associated with the
      presence of synovitis at the first visit. There were no significant differences
      in the seroprevalence rates of antibodies to C. pneumoniae, CMV, EV or RSV
      between PMR patients and controls. IgM antibodies to EV were found in two
      patients and IgM antibodies to CMV in another two patients. CONCLUSION:
      Serological evidence of an association between newly-diagnosed PMR and prior or
      chronic infection with C. pneumoniae was not found. IgM antibodies to EV in two
      patients, consistent with ongoing or recent infection, suggest that EV could
      represent one of perhaps several microbes which are able to trigger PMR.

PMID- 9177927
TI  - Efficacy and adverse effects of different corticosteroid dose regimens in
      temporal arteritis: a retrospective study.
AB  - OBJECTIVE: To define the optimal corticosteroid dose regimen in the initial
      treatment of temporal arteritis (TA). METHODS: We conducted a retrospective long
      term evaluation of the efficacy and toxicity of corticosteroid treatment in 77 TA
      patients treated with three different dose-regimens: group A starting at 30-40
      mg/d of prednisone, group B > 40-60 mg/d, and group C > 60 mg/d. RESULTS: The 3
      patient groups were similar with regard to the mean age, male/female ratio, mean
      duration of follow-up, percentage of positive temporal artery biopsies, and rate
      of steroid tapering. There was a positive correlation between the starting dose
      and the cumulative dose of steroids at one year. Treatment efficacy was similar
      among the groups: cumulative cure rates (i.e. patients off steroids without
      exacerbation of TA for 6 months or more) were 11-13%, 29-35%, and 48-50% after 1,
      2, and 3 years, respectively. In addition, the rates of disease flare were
      similar among the groups after 3 years of follow up, although group C patients
      tended to have fewer TA exacerbations during the first year compared to the other
      groups. In contrast, group A patients developed significantly fewer steroid side
      effects: 36% compared to 78% and 88% in groups B and C. CONCLUSION: The group A
      steroid regimen, starting with 30-40 mg/d and tapering to 10 mg/d within 6 months
      and to 5-7.5 mg/d within 1 year, was effective and less toxic in this patient
      population, than the two higher dose regimens.

PMID- 9177928
TI  - Crohn's disease associated with seropositive rheumatoid arthritis.
AB  - We report two cases of rheumatoid arthritis (RA) associated with Crohn's disease
      (CD). The first case was a 60-year-old man with longstanding CD who next
      developed a seropositive, nodular RA. This patient also had bilateral
      sacroiliitis, but without positive HLA B27. The second was a 65-year-old female
      with a 15-year history of seropositive RA who presented secondarily a CD. No
      sacroiliitis or nodules were found in this patient. Both patients were DR1 (DRB1*
      0101). Gold salts were only given in the second case and were stopped many years
      before the gastrointestinal symptoms. A similar case report has been previously
      described consisting in an ulcerative colitis complicating a seronegative HLA-B27
      RA with sacroiliitis. The gastrointestinal involvement in RA may be broad and
      includes many causes: drug-induced colitis (including gold enterocolitis)
      vasculitis and amyloidosis located in the gut, associated bowel disease such as
      collagenous colitis, and also infectious agents. In addition, erosive
      polyarthritis associated with gastrointestinal manifestations can present a
      problem in the differential diagnosis between RA and an enteropathic arthritis.
      Finally, the coexistence by chance of inflammatory bowel disease and RA is
      suggested by the low occurrence of these two conditions in the same patient.

PMID- 9177929
TI  - Primary biliary cirrhosis and systemic lupus erythematosus. A rare association.
AB  - Although the co-existence between primary biliary cirrhosis (PBC) and one or more
      autoimmune diseases is very common, the association with systemic lupus
      erythematosus (SLE) is believed to be rare. We describe a 37-year-old woman with
      PBC who developed clinical and serological features of SLE 4 years later. The
      anti-mitochondrial antibody (AMA) titers fell to undetectable levels during the
      acute phase of the SLE. At the same time, high titers of antinuclear antibodies
      (ANA) were detected. Changes in opposite directions in the AMA and ANA titers
      were also seen during remission of the SLE.

PMID- 9177930
TI  - Glucocorticoids and Th-1, Th-2 type cytokines in rheumatoid arthritis,
      osteoarthritis, asthma, atopic dermatitis and AIDS.
AB  - Endogenous or exogenous glucocorticoids play a key role in the control of the
      immune and inflammatory network. Regulation of the effects of the glucocorticoids
      depends on changes in therapeutic levels, but also, as recently discovered, on
      modifications of the binding characteristics of the glucocorticoid receptors of
      target cells. In rheumatoid arthritis (RA), chronic bronchial asthma, atopic
      dermatitis, in chondrocytes from osteoarthritic patients, and in advanced stages
      of HIV infection, there is a down-regulation of the glucocorticoid receptors. As
      a consequence, B cell immune proliferation is stimulated in RA, proteolysis is
      enhanced in osteoarthritis, the glucocorticoids' therapeutic effect is reduced in
      asthma and atopic dermatitis, and a chronic persistent increase of interferon
      alpha is seen in HIV. Finally, glucocorticoids are also capable of switching CD4
      cells from a Th-1 to a Th-2 pattern. A decreased affinity of lymphocyte
      glucocorticoid receptors could hinder such a switch, with obvious clinical
      implications.

PMID- 9177931
TI  - Serum content of the C-propeptide of the cartilage molecule type II collagen in
      children.
AB  - OBJECTIVE: The C-propeptide of cartilage type II procollagen, together with the N
      propeptide, are removed from newly synthesized procollagen during collagen fibril
      assembly in cartilage matrix. The presence and content of the C-propeptide
      reflect the synthesis of this molecule. Recently, we showed that serum levels of
      the C-propeptide are increased in adults with rheumatoid arthritis, pointing to
      increased synthesis of this molecule. In this study we examined its content in
      the sera of children to determine whether it changes during development. METHODS:
      Sera were obtained from 44 premature infants (cord blood), 75 children (0-18
      years), 14 young adults (18-22 years) and 47 adults (35-60 years). The
      concentration of serum C-propeptide of type II procollagen was determined by a
      solution phase competitive inhibition radioimmunoassay which uses a polyclonal
      antiserum specific for the bovine and human C-propeptide. RESULTS: Compared with
      adults, concentrations of the C-propeptide of type II procollagen were
      significantly elevated in children of ages 0-14 years. Concentrations were
      constant until 10 years of age (premature infants: 14.5 +/- 1.4 ng/ml, mean +/-
      SE; 0-10 years: 13.6 +/- 1 ng/ml). In children of ages 10-14 years, during which
      the pubertal growth spurt is ordinarily observed, the mean concentration
      increased (10-14 years: 21.6 +/- 0.7 ng/ml) although not significantly due to the
      variation between individuals. Concentrations at all ages younger than 14 were
      significantly greater than those in older adolescents ages 14-18 (6.3 +/- 0.7
      ng/ml), young adults (8.4 +/- 2.0 ng/ml) and adults (5.7 +/- 0.4 ng/ml). Serum
      concentrations did not show significant differences with respect to sex, but
      varied from child to child at any given age. CONCLUSIONS: The measurement of this
      circulating C-propeptide may be of use in studying the biochemical and
      physiological bases of changes in cartilage turnover in children, and
      abnormalities thereof.

PMID- 9177932
TI  - Erythema multiforme-like manifestations and arthritis in a 3-year-old child with
      leukocytoclastic vasculitis.
AB  - A 3-year-old boy with erythema multiforme-like manifestations and severe
      articular involvement is reported. Because of the unusual onset of the cutaneous
      lesion a skin biopsy was performed, revealing the typical features of a
      leukocytoclastic vasculitis. A direct immunofluorescent study revealed C3 and IgM
      deposition within the wall and around the small vessels. The clinical and
      immunopathological findings in this patient were similar to those reported for
      the acute hemorrhagic edema of infancy (AHE) described in children younger than 2
      years of age. The present case supports the hypothesis that AHE is a distinctive
      leukocytoclastic vasculitis of childhood, irrespective of the age at onset.

PMID- 9177933
TI  - Study of HHV-8 in primary Sjogren's syndrome.

PMID- 9177934
TI  - Relapsing polychondritis: a syndrome rather than a distinct clinical entity?

PMID- 9177935
TI  - Polyglandular autoimmune syndrome type II and rheumatoid arthritis.

PMID- 9177936
TI  - A case of scleroderma associated with sarcoidosis.

PMID- 9177937
TI  - Lack of association between chronic hepatitis C virus infection and Behcet's
      disease.

PMID- 9177938
TI  - Interosseous nerve entrapment syndromes complicating inflammatory arthritis.

PMID- 9177939
TI  - Chemoprevention of human cancer: biology and therapy.

PMID- 9177940
TI  - Apoptosis in metastatic cancer cells.

PMID- 9177941
TI  - Biologic and oncologic implications of tenascin-C/hexabrachion proteins.

PMID- 9177942
TI  - Achalasia: what's new in diagnosis and treatment?
AB  - Achalasia is an esophageal motility disorder of unknown cause, characterized
      clinically by dysphagia and regurgitation and diagnosed by manometry and/or
      barium esophagogram. Good long-term symptomatic relief can be achieved with
      pneumatic dilatation and myotomy. Botulinum toxin injection and videoendoscopic
      surgery are being evaluated as less invasive forms of therapy.

PMID- 9177943
TI  - Recent developments in the manometric assessment of upper esophageal sphincter
      function and dysfunction.
AB  - Coordinated application of videoradiography and solid-state manometry provides
      insight into the pathophysiology of oropharyngeal dysphagia and helps direct
      appropriate therapies for a variety of conditions causing this symptom.
      Controlled evaluations of various treatment modalities, however, are lacking and
      therapy often remains primarily empiric. Despite this limitation, important
      strides have been made in the overall management of these patients during the
      past decade.

PMID- 9177944
TI  - Contributing role of motility abnormalities in the pathogenesis of
      gastroesophageal reflux disease.
AB  - Although many factors are involved in the pathogenesis of gastroesophageal reflux
      disease (GERD), the antireflux barrier at the gastroesophageal junction is the
      final determinate of reflux. In the majority of cases, transient lower esophageal
      sphincter (LES) relaxations appear to be the necessary condition for reflux to
      occur. In severe cases of GERD, especially those with esophagitis, stricture, and
      Barrett's epithelium, diminished resting LES pressure plays a contributory role.
      Esophageal dysmotility may be an additive factor leading to increased esophageal
      acid contact time and predispose patients to developing erosive esophagitis.
      Also, delayed gastric emptying may further compromise the LES. Finally, the role
      of bile reflux across an incompetent gastroduodenal (pyloric) junction remains
      controversial.

PMID- 9177945
TI  - Antroduodenal manometry: an evaluation of an emerging methodology.
AB  - Antroduodenal manometry is a relatively new technique for the assessment of
      gastric and small intestinal motor function. The aim of this review is to provide
      an evaluation of its current status as a diagnostical tool. Available recording
      systems are reviewed and the study protocol for the evaluation of antroduodenal
      motor function is described. The role of this methodology in the evaluation of
      patients with suspected motor disorders, its advantages over other less invasive
      techniques and limitations are critically assessed. We conclude that, in the
      evaluation of suspected foregut motor dysfunction, antroduodenal manometry may
      provide clinically useful information in selected patients; information which may
      not be available from standard diagnostic tests, including nuclear medicine
      gastric-emptying studies.

PMID- 9177946
TI  - Current techniques of assessing defecation dynamics.
AB  - The pathophysiology of defecation disorders is multifactorial. An ideal test
      should identify the underlying cause(s) and provide guidelines for treatment.
      Unfortunately, there is no such single test. But several techniques are available
      that could provide comprehensive information regarding the changes in defecation
      dynamics. Among these, anorectal manometry offers the most useful test for
      clinicians. Manometry may provide objective evidence for impaired rectal
      sensation, poor rectoanal coordination, weak anal sphincters or changes that
      support a diagnosis of obstructive defecation. Other tests such as the balloon
      expulsion test may serve as screening tools for patients with constipation. In a
      patient with fecal incontinence, anal endosonography may localize the sphincter
      defect and aid surgical reconstruction. The pudendal nerve latency test may
      provide a pathophysiological basis for a weak anal sphincter. Imaging techniques
      such as defecography may provide useful information regarding rectal prolapse or
      levator ani dysfunction. Ideally, the clinician should utilize these tests either
      to confirm a clinical suspicion or to provide new information that could aid
      management. This review provides an update regarding the various tests that are
      available for assessing defecation and provides some practical guidelines for
      performing manometry.

PMID- 9177947
TI  - Biofeedback therapy for defecation disorders.
AB  - Biofeedback therapy is a useful adjunct to conventional treatment for many
      patients with refractory defecation disorders. This article provides an overview
      regarding the historical evolution of this treatment together with current
      perspectives regarding the principles and techniques of performing biofeedback
      therapy and an assessment of its outcome in adults and pediatric patients with
      defecation disorders.

PMID- 9177948
TI  - Current advances and controversies in the surgical therapy for anorectal motility
      disorders.
AB  - It is the goal of this review to discuss the increasingly common problem of
      anorectal motility disorders and their potential surgical management. Perhaps the
      most important goal in patients with anorectal motility disorders is to
      categorize them accurately into etiologic groups. The reason is that approaches
      to medical and surgical therapy are highly dependent on accurate categorization
      of these patients with motility disorders. This review is written from the
      perspective of a surgical practice which sees a high volume of patients with
      anorectal motility disorders and has a very logical, nearly algorithmic approach
      to the evaluation and management of these patients. The review is not exhaustive,
      nor does it include all possible alternatives. It is meant to be a relatively
      practical guide to physicians and surgeons who deal with patients with anorectal
      motility disorders and is based on the experience of surgeons and
      gastroenterologists who see large numbers of these patients.

PMID- 9177949
TI  - Role of colonic motility in guiding therapy in patients with constipation.
AB  - Constipation is a common condition defined by less than three bowel movements per
      week. Often constipation is secondary to altered motility of the colon. Tests
      that measure colonic motility lead the clinician to appropriate therapy. Colonic
      transit measured with either radionuclides or radio-opaque markers determine
      whether the transit through the colon is truly slow, and then identify the
      potential region of the colon that impedes the movement of intraluminal contents.
      Patients with normal colonic transit do not require further evaluation of their
      colonic motor function. Colonic and anorectal manometry differentiate patients in
      to 3 groups: (1) functional anal outlet obstruction; (2) uncoordinated distal
      colonic phasic contractions, and (3) colonic inertia. Functional outlet
      obstruction may be treated successfully by increasing the water content of their
      stools and biofeedback. Antispasmodics including anticholinergics, nitrates and
      calcium channel blockers may decrease the functional obstruction caused by phasic
      colonic contractions. The prokinetics such as cisapride have successfully
      improved constipation due to colonic inertia, Parkinson's disease or spinal cord
      injury as well as idiopathic inertia. Occasionally patients with inertia may
      require colectomy with ileorectal anastomosis to treat severe constipation.

PMID- 9177950
TI  - Pharmacological stimulation of gastrointestinal motility: where we are and where
      are we going?
AB  - Drugs affecting gastrointestinal motility have become valuable in the management
      of a number of diseases. Medications that enhance the transit of material through
      the gastrointestinal tract are called prokinetics. Although symptom improvement
      can be seen in a variety of motility disorders, these medications have not shown
      a selective benefit for a particular motility disturbance or symptom complex.
      This class of drugs includes several subclasses, each with a distinct mechanism
      of action. Amongst the existing prokinetic compounds, dopamine antagonists, on
      the one hand, and cholinomimetic drugs, on the other hand, should be
      distinguished. Since compounds endowed with dopamine antagonism have the
      disadvantage of causing neuroendocrine side effects and/or extrapyramidal
      dyskinetic reactions (seen especially after metoclopramide), the recently
      developed non-cholinergic non-antidopaminergic compound, cisapride, seems to be
      the most effective one. Its main mechanism of action is considered to be the
      stimulation of myenteric cholinergic nerves with consequent increase of
      acetylcholine release. Recent evidence suggests that blockade of CCK receptors
      and stimulation of motilin receptors are also promising avenues to increase
      gastrointestinal motility. Since drugs acting on 5-HT receptors are presently the
      best available motor-stimulating compounds, new derivatives are being developed
      as gastrokinetic drugs. Although the long-acting somatostatin analog, octreotide,
      and the GnRH agonist, leuprolide, have shown prokinetic properties in particular
      clinical conditions, their widespread use cannot be recommended at present.
      Further work is needed to determine the predictive value of objective
      abnormalities for the efficacy of a drug in the individual patient. This is the
      crucial point to define a rational strategy in clinical practice, especially to
      establish if functional investigation is needed before a prokinetic drug be
      given.

PMID- 9177951
TI  - Three-dimensional visualization and quantification of the benzodiazepine receptor
      population within a living human brain using PET and MRI.
AB  - Positron emission tomography (PET) in combination with receptor-selective high
      affinity radioligands allows the characterization of neuroreceptor distributions
      in the living human brain. Thus far, the visualization and quantification of
      receptors with PET have been limited to series of two-dimensional (2D) image
      planes of the anatomic receptor distribution. The development of high-resolution
      PET has increased the number of planes to approximately 50, supplying an
      excessive amount of image information from a single experiment. The inherent
      limitations of 2D techniques make them insufficient to apprehend and efficiently
      analyze this cumbersome amount of data. In the present communication we describe
      procedures to visualize and quantify in three dimensions (3D) the total image
      information from the compound set of 47 2D planes of a PET experiment using
      commercially available software. Three-dimensional computer graphic and volume
      rendering techniques were used to analyze and display the results. For the
      experimental application the benzodiazepine (BZ) antagonist [11C]flumazenil was
      used as radioligand to visualize the BZ receptor (BZR) population in the brain of
      a healthy human subject. Three-dimensional images of the radioligand binding
      receptor population were displayed with regard to volume and form in relation to
      the corresponding anatomic structures in the brain reconstructed from MR images.
      The volume-rendering technique allowed the inspection of PET signals representing
      BZR populations in the interior of the hemisphere as viewed from the medial
      projection. Thresholding and seeding techniques were used to define volumes and
      quantities. Using the PET data and volume rendering, the total amount of cerebral
      BZRs (NCerebrum) and the apparent volume they take into account (V(BZR,
      Cerebrum)app) could he calculated for the first time using an automated
      procedure. The cerebrum of the healthy subject contained 17.6 nmol of BZRs in a
      volume of approximately 1.25 L. The principles and application of the technical
      development described offer new dimensions to clinical neuroscience and should be
      practically useful for automated quantitative determination of neuroreceptor
      number in brain regions of patients with neuropsychiatric disorders and in
      relation to drug treatment.

PMID- 9177952
TI  - The International Multicenter Clinical Trial Group on Moclobemide in Social
      Phobia. Moclobemide in social phobia. A double-blind, placebo-controlled clinical
      study.
AB  - The primary objectives of this large multicenter study (n = 578) were to
      determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the
      treatment of social phobia. A double-blind fixed-dose parallel group study was
      conducted to compare the two different doses of moclobemide to placebo. After a 1
      week placebo run-in period, patients were randomly assigned to one of the three
      treatment groups to receive the test compound for a 12-week period. Assessments
      were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12.
      There were consistent, reliable and clinically meaningful drug effects and
      indications of a dose-response relationship. Statistical analysis of the results
      at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and
      statistically significantly superior to placebo. The 300 mg dose also showed
      better efficacy than placebo on all measures of efficacy, and about half of them
      were statistically significantly different from placebo. Moclobemide was well
      tolerated. Adverse events, except for insomnia, were neither dose-related nor
      were there significant drug-placebo differences. The results indicate that 600 mg
      of moclobemide per day given b.i.d. is effective in social phobia, reducing the
      symptoms and the impairment associated with the disorder. The compound is well
      tolerated and safe.

PMID- 9177953
TI  - The Zurich Study. XXIV. Structural and emotional aspects of childhood and later
      psychopathology.
AB  - A Swiss cohort interviewed four times between ages 20 and 30 years reported on a
      structural aspect of childhood (separation from parents) and emotional aspects
      (family strain, childhood behavioral and emotional problems). These data were
      connected with DSM-III-R diagnoses of anxiety and depression, SCL-90R scores (all
      repeatedly ascertained) and with Freiburg Personality Inventory results at age 30
      years. Adult psychopathology, personality deviations, and negative affectivity
      were not connected with early or later separation, but with a report of family
      strain and childhood disturbances. As variables associated with later psychiatric
      symptoms and disorder, interpersonal and subjective aspects of childhood out
      weigh the fact of separation from parents.

PMID- 9177954
TI  - Selection bias during recruitment of elderly subjects from the general population
      for psychiatric interviews.
AB  - The aim of the present study was to determine and assess a possible selection
      bias in an epidemiologic investigation in the elderly. A stratified sample of
      1305 probands aged 60-99 years was initially contacted by mail and then by
      telephone to obtain their consent to participate in a psychiatric interview. A
      liberal recruitment procedure led to interview participation of only 291
      subjects. The proportion of younger, male, and married subjects participating in
      the study was greater than that of elderly, female, and single or widowed
      subjects. Subjects without a psychiatric lifetime diagnosis were more cooperative
      than those with a psychiatric disorder. The latter finding demonstrates the need
      to determine and assess the selection bias in psychiatric epidemiologic studies
      in elderly subjects.

PMID- 9177955
TI  - Psychopharmacoepidemiology in Iceland: effects of regulations and new
      medications.
AB  - The sale of psychotropic medications in Iceland has waxed and waned during the
      past 20 years with approximately 5 years between peak and bottom quantities sold.
      Apparently, it has decreased following restrictions imposed by the public health
      authorities and increased again following the introduction of new drug. In order
      to study this further, all prescriptions for psychotropic medications to non
      hospitalized inhabitants of the capital city (Reykjavik) and dispensed by
      pharmacists there during 1 month in 1984, 1989 and 1993 were analysed in order to
      estimate the 1-month prevalence of psychopharmacological use. The results support
      the hypothesis partly as prescriptions for tranquillizers decreased in 1989 as
      well as the amount of tranquillizers and hypnotics prescribed following new
      restrictions, whereas the prevalence odds ratio of obtaining prescriptions for
      hypnotics remained unchanged. The proportion of patients receiving excessive
      amounts of tranquillizers and/or hypnotics decreased. The prevalence of excessive
      use of these drugs (i.e. > 90 DDD/month) was 0.5% in 1993. In 1993 the prevalence
      of the use of antidepressants as well as the amount prescribed had increased
      substantially following the introduction of the new selective serotonin reuptake
      inhibitor medications. Thus, the prevalence of patients obtaining any
      psychotropic medication remained unchanged from 1984 to 1993.

PMID- 9177956
TI  - Sleep deprivation hastens the antidepressant action of fluoxetine.
AB  - Among ten bipolar depressed patients admitted to our psychiatric ward, five
      patients were treated with fluoxetine alone and five subjects were treated with
      fluoxetine in association with total sleep deprivation (TSD) in order to evaluate
      the effect of the interaction between the administration of the serotonergic
      antidepressant compound fluoxetine and repeated cycles of TSD. Patients treated
      with fluoxetine plus repeated TSD showed a faster amelioration of depressive
      symptomatology compared with the other group. We discuss our findings
      hypothesizing an enhancement in dopaminergic and possibly in serotonergic
      transmission due to repeated TSD adding to the increase in serotonergic
      transmission due to fluoxetine medication.

PMID- 9177957
TI  - D2-dopamine-receptor occupancy during treatment with haloperidol decanoate.
AB  - We investigated in an open, explanatory study a total of 24 patients meeting DSM
      III-R criteria for schizophrenia. Eighteen patients were treated for at least 4
      weeks with a fixed dose of orally administered haloperidol for at least 4 weeks
      (mean daily dosage ranging from 0.07 to 0.35 mg/kg b.w.), and 6 patients received
      haloperidol decanoate with a fixed dose for at least 4 months (dosage range 50
      150 mg/4 weeks; calculated mean daily dosage ranging from 0.02 to 0.09 mg/kg
      b.w.). One week after injection of haloperidol decanoate, the single photon
      emission computed tomography examination was performed. Our data suggest that D2
      dopamine-receptor occupancy of 50 mg/4 weeks haloperidol decanoate 1 week after
      injection corresponds to an oral dose of 4.5 mg/day haloperidol.

PMID- 9177958
TI  - Auditory event-related potentials in panic disorder.
AB  - To investigate the psychophysiological features of panic disorder (PD), we
      recorded auditory event-related potentials (ERPs) in 12 patients with PD meeting
      the DSM-IV criteria and in 12 age-matched normal controls. The ERPs were recorded
      during a standard two-tone discrimination task (oddball task). The probabilities
      of the rare target (1200 Hz) and frequent non-target tones (1000 Hz) were 15 and
      85%, respectively. The subjects were required to press a button in response to
      the rare target tones. Scalp electroencephalograms were recorded from Fz, Cz, Pz,
      C3, and C4. The State-Trait Anxiety Inventory and Manifest Anxiety Scale scores
      were assessed for clinical evaluation. Analysis of variance revealed that the N1
      and N2 amplitudes for target tones and the N1 amplitude for non-target tones were
      significantly larger in the PD patients than those in the controls. The two
      groups did not differ significantly in P3 latency and amplitude. The larger N1
      and N2 amplitudes in the PD patients are suggestive of alteration of early
      information processing in PD.

PMID- 9177960
TI  - When should Candida isolates be tested for susceptibility to azole antifungal
      agents?

PMID- 9177961
TI  - Five-day versus ten-day treatment of acute otitis media with cefprozil.
AB  - A randomized comparative clinical trial was conducted to investigate the
      possibility of decreasing the duration of treatment of acute otitis media by
      comparing the clinical outcome and safety of a five-day and a ten-day course of
      cefprozil. A total of 708 pediatric patients were enrolled in the study, 560 of
      whom were evaluable for efficacy. Cefprozil was found to be completely effective
      in 87.1% of cases after five days of treatment, and in 91.2% after ten days of
      treatment. Of 19 patients with three or more previous episodes of acute otitis
      media, ten patients in the ten-day treatment group had a 100% cure rate, while in
      the five-day group four experienced cure, three improvement, and two failure. A
      five-day course of treatment with cefprozil can be recommended only if children
      have no history of recurrent acute otitis media.

PMID- 9177959
TI  - Azole resistance in Candida.
AB  - Resistance of Candida to azoles is an increasing problem. Susceptibility testing
      of Candida against fluconazole and ketoconazole is now feasible and desirable.
      Good correlation of resistance in vitro with clinical failure of fluconazole
      therapy has now been shown in mucosal candidiasis. The relationship, if any,
      between resistance and clinical failure in the context of invasive candidiasis is
      not clear at present and additional correlative work needs to be done. Monitoring
      of resistance trends in Candida is clearly important now.

PMID- 9177962
TI  - Large-scale multicentre study of fluconazole in the treatment of hospitalised
      patients with fungal infections. Multicentre European Study Group.
AB  - The purpose of this prospective, open-label, noncomparative, multicentre study
      was to evaluate the efficacy and safety of fluconazole in the treatment of
      hospitalised patients with mycoses. A total of 587 patients with diagnosed fungal
      infections were enrolled. Fluconazole was given orally or intravenously in a 200
      or 400 mg loading dose, followed by 100 or 200 mg once daily. The most common
      candidal infections were fungemia, esophageal candidiasis, bronchopulmonary
      candidiasis, peritonitis, oropharyngeal candidiasis, urinary tract infection and
      deep wound infection. Meningitis was the most common cryptococcal infection. Of
      the 291 evaluable patients with candidiasis, 96% (70/73) of AIDS patients and 79%
      (171/218) of non-AIDS patients were clinically cured or improved. Of the 36
      evaluable patients with cryptococcosis, 69% (20/29) of AIDS patients and 100%
      (7/7) of non-AIDS patients responded clinically. The overall mycological
      eradication rate was 85%; eradication was similar in patients with and without
      AIDS. Most adverse events during fluconazole therapy were mild to moderate in
      severity. This investigation confirms the results of previous studies
      demonstrating high response rates to fluconazole therapy in AIDS and non-AIDS
      patients with fungal infections. Even during long-term therapy treatment-limiting
      adverse events were uncommon with fluconazole.

PMID- 9177963
TI  - Use of specialised isolation media for recognition and identification of Candida
      dubliniensis isolates from HIV-infected patients.
AB  - During a study of oral rinses of 130 HIV-infected individuals, both typical and
      atypical Candida albicans colonies were isolated from ten patients on a yeast
      differential medium. Typical Candida albicans colonies were light green; atypical
      colonies were dark green. Both types of colonies were germ tube-positive and
      produced chlamydospores. However, DNA fingerprinting of the atypical isolates
      with the Ca3 Candida albicans-specific probe showed that they belonged to the
      recently described species Candida dubliniensis. Candida dubliniensis colonies
      could also be differentiated from Candida albicans colonies on isolation plates
      by the absence of fluorescence of colonies on methyl blue-Sabouraud agar under
      Wood's light. Among other phenotypic characteristics, only the absence of
      intracellular beta-glucosidase activity reliably distinguished Candida albicans
      from Candida dubliniensis. Candida dubliniensis may be underreported in clinical
      samples because most currently used isolation and identification methods fail to
      recognize this yeast.

PMID- 9177964
TI  - Comparison of screening methods to identify methicillin-resistant Staphylococcus
      aureus.
AB  - Screening methods to identify methicillin-resistant Staphylococcus aureus (MRSA)
      were compared using 96 isolates representing 17 distinct clones. The sensitivity
      of four commercial agglutination tests was determined in comparison to the tube
      coagulation test, and the results related to the presence of the coagulase gene.
      The broth screening test, agar dilution test and disc diffusion test were carried
      out, and the results related to the presence of the mecA gene. Mannitol salt agar
      and Iso-Sensitest agar with varying salt supplements were used. All agglutination
      tests had high rates of detection of Staphylococcus aureus (95.8-99.0%).
      Resistance in mecA gene-positive Staphylococcus aureus isolates was correctly
      detected by the oxacillin broth test, the agar dilution test and the disc
      diffusion test on mannitol salt agar, whereas on Iso-Sensitest agar detection
      rates were lower (between 68.5% and 94.4%, depending on the salt supplement).
      Incubation of the Iso-Sensitest plates for 48 hours significantly improved the
      rate of detection of resistance, but increased the major error rate up to 71.4%.
      MecA gene-positive Staphylococcus aureus isolates not detected by the disc
      diffusion test on Iso-Sensitest agar had significantly lower oxacillin minimal
      inhibitory concentration values and were significantly less resistant to a
      variety of antibiotics. Thus, mannitol salt agar might be a suitable medium for
      use in the disc diffusion and agar dilution test to detect resistance to
      oxacillin in Staphylococcus aureus.

PMID- 9177965
TI  - Cervical lymphadenitis due to an unusual mycobacterium.
AB  - A scotochromogenic acid-fast bacillus was isolated from a lymph node of a 2-year
      old female. On the basis of conventional testing, the mycobacterium appeared to
      be Mycobacterium scrofulaceum. Its mycolic acid profile, however, was not
      identical to that of Mycobacterium scrofulaceum but was similar to that of
      Mycobacterium interjectum. Direct sequencing of the 16S rRNA gene revealed a
      unique nucleic acid sequence, suggesting that the isolate represents a previously
      undescribed pathogenic species.

PMID- 9177966
TI  - Assessment of the oxacillin disk screening test for determining penicillin
      resistance in Streptococcus pneumoniae.
AB  - The 1 microgram oxacillin disk diffusion screening test was performed on 1516
      recent clinical isolates of Streptococcus pneumoniae obtained in a 1994-1995 U.S.
      surveillance study and the results compared to penicillin MICs determined using a
      standardized broth microdilution method. The oxacillin disk screening method
      failed to distinguish penicillin-resistant strains from those that were
      intermediately susceptible. Furthermore, a high percentage (11.1%) of penicillin
      susceptible strains, for which MICs of penicillin were usually 0.06 or 0.03
      microgram/ml, yielded zone diameters of < or = 19 mm with the oxacillin screen
      test and thus would have been falsely categorized as being resistant to
      penicillin.

PMID- 9177967
TI  - Selection of Candida glabrata strains with reduced susceptibility to azoles in
      four liver transplant patients with invasive candidiasis.
AB  - The cases of four liver transplant recipients who developed invasive candidiasis
      (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistant,
      Candida glabrata are reported. Three patients were receiving azolic compounds (2
      itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients
      received fluconazole as intestinal decontamination during the first three weeks
      post transplantation. The infections occurred two months after transplantation in
      all patients, and in one patient Candida infection was the direct cause of death.
      Infection of the biliary tree was the origin of candidiasis in three patients;
      the fourth patient developed neutropenic-related candidemia. Fluconazole MICs
      exceeded 16 micrograms/ml in all cases; itraconazole MICs were 16, 2, 1, and 2
      micrograms/ml, respectively. The potential role of Candida species other than
      albicans in these patients after administration of azole agents is discussed.

PMID- 9177968
TI  - Determination of the number of blood samples needed for optimal detection of
      cytomegalovirus viremia in immunocompromised patients using a shell-vial assay.
AB  - To establish the number of blood samples necessary for the diagnosis of viremic
      episodes caused by cytomegalovirus (CMV), a prospective analysis was conducted of
      238 patients (38 renal transplant recipients and 200 HIV-infected patients) who
      developed CMV viremia. The usefulness of samples and the volume of blood required
      to demonstrate the presence of viremia by CMV was also studied. The first blood
      sample was diagnostic for CMV viremia in 53.3% of the viremic patients; the
      second sample documented an additional 22.2% of cases of viremia (75.5% of
      infected patients); and the third sample demonstrated viremia in the remaining
      24.5%. Thus, a diagnosis of CMV viremia was established in every patient (100% of
      episodes of viremia). In this study, the use of three 3 ml blood samples
      collected at 24 h intervals was sufficient to detect all episodes of CMV viremia
      in patients clinically suspected to have disseminated disease.

PMID- 9177969
TI  - A case of Alternaria keratitis treated with fluconazole.

PMID- 9177970
TI  - Group A streptococcal meningitis and toxic shock syndrome caused by a protein M
      type 3 strain producing exotoxin C.

PMID- 9177971
TI  - A case of bacteremia caused by Streptococcus dysgalactiae.

PMID- 9177972
TI  - Seroprevalence of immunoglobulin G antibodies to Bartonella henselae in cat
      owners.

PMID- 9177973
TI  - Herpes simplex meningitis after surgical removal of a clivus chordoma.

PMID- 9177974
TI  - In vitro methods for confirming reduced susceptibility to cefuroxime among
      Haemophilus influenzae isolates.

PMID- 9177975
TI  - A critical appraisal of current management practices for infant regurgitation-
      recommendations of a working party.
AB  - Regurgitation is a common manifestation in infants below the age of 1 year and a
      frequent reason of counselling of general practitioners and paediatricians.
      Current management starts with postural and dietary measures, followed by
      antacids and prokinetics. Recent issues such as an increased risk of sudden
      infant death in the prone sleeping position and persistent occult gastro
      oesophageal reflux in a subset of infants receiving milk thickeners or thickened
      "anti-regurgitation formula" challenge the established approach. Therefore, the
      clinical practices for management of infant regurgitation have been critically
      evaluated with respect to their efficacy, safety and practical implications. The
      updated recommendations reached by the working party on the management of infant
      regurgitation contain five phases: (1 A) parental reassurance; (1 B) milk
      thickening agents; (2) prokinetics; (3) positional therapy as an adjuvant
      therapy; (4 A) H2-blockers; (4 B) proton pump inhibitors; (5) surgery.

PMID- 9177976
TI  - Final height outcome in girls with Turner syndrome treated with a combination of
      low dose oestrogen and oxandrolone.
AB  - Final stature in girls with Turner syndrome treated with combination of low dose
      oestrogen and oxandrolone. Nineteen prepubertal girls with Turner syndrome (mean
      age 10.9 years, range, 8.9-14.2 years) were randomly assigned to receive either
      oxandrolone (0.05 mg/kg/day) or ethinyloestradiol (40 ng/kg/day) for 1 year.
      Subsequently the alternate therapy was added and the combination given until
      attainment of final height. Ethinyloestradiol was gradually increased at the age
      of 12.5 years in order to induce secondary sexual characteristics. The duration
      of treatment was a mean of 5.2 years (range, 3.7 years) when the 1st year of
      monotherapy was included. Therapy produced a sustained acceleration in growth
      rate for a duration of 4 years and eventually has resulted in an increment of
      mean adult height of 3 cm relative to pre-treatment projected height with mean
      values of 146.5 cm versus 143.5 cm respectively. The moderate side-effects
      observed did not cause any of the girls to discontinue treatment. Nevertheless,
      amelioration of adult height appears to be modest, notably in comparison to
      published data of growth hormone treatment and 4 girls had a decrease in final
      height prediction. CONCLUSION Combination of low dose of oxandrolone and
      oestrogen may have a moderate but positive impact on final height in girls with
      Turner syndrome. However, some girls do worse than predicted in term of final
      height using this regimen. Oestrogen therapy started at low dose around the age
      of 10 years and increased gradually at approximately 12.5 years to induce
      secondary sexual characteristics does not have a deleterious effect on adult
      height in Turner syndrome. In summary, low dose oxandrolone-oestrogen treatment
      was found to accelerate the tempo of growth in girls with Turner syndrome, but
      did not appear to have a consistent effect on final height.

PMID- 9177977
TI  - Pseudohypo-aldosteronism and cholelithiasis: coincidence or pathogenetic
      correlation?
AB  - Cholelithiasis is being documented with increasing frequency in the paediatric
      age group. Causes of gallstone formation in infants and neonates seem to differ
      from those in older children and adolescents. Two infants with pseudohypo
      aldosteronism and cholelithiasis are reported. Salt-wasting and dehydration in
      pseudohypo-aldosteronism are suggested to be the pathogenetic mechanisms leading
      to gallstone formation possibly beginning in fetal life. The diagnosis of
      pseudohypo-aldosteronism may be missed, when salt-wasting is transitional.
      Cholelithiasis may go undetected when asymptomatic. CONCLUSION Pseudohypo
      aldosteronism should be considered in infants with cholelithiasis even without
      obvious salt-wasting signs. Routine ultrasonographic screening for gallstones
      should be performed in patients with pseudohypo-aldosteronism.

PMID- 9177978
TI  - Cerebral haemorrhage in long-term survivors of childhood acute lymphoblastic
      leukaemia.
AB  - Modern treatment of childhood acute lymphoblastic leukaemia (ALL) has
      dramatically improved the prognosis for children with this disease. Therapeutic
      approaches consist of multimodal chemotherapy and radiotherapy with significant
      long-term side-effects. We report on 4 children out of a group of 120 newly
      diagnosed patients with ALL, who survived the disease for more than 2 years and
      developed a cerebral haemorrhage after chemotherapy and fractionated cranial
      irradiation. Following a period of 2-12 years the four children presented with
      acute neurological signs and symptoms. i.e. seizures, ataxia and hemiparesis. CT
      and MRI revealed intracerebral mass lesions, interpreted as haemorrhage. After
      neurosurgery the patients neurological state improved. Histological examination
      confirmed the suspected diagnosis of bleeding cavernous haemangioma or capillary
      telangiectases. There are two possibilities to explain these rare alterations:
      they may be pre-existent to the disease and therapy or they may be caused by
      irradiation. CONCLUSION Acute neurological symptoms in patients treated for ALL
      may be caused by spontaneous cerebral haemorrhaging of cavernous haemangiomas or
      capillary telangiectases induced by chemotherapy and/or radiotherapy.

PMID- 9177979
TI  - Abnormal insulin response to glucose following treatment for Wilms' tumor in
      childhood.
AB  - To determine whether beta-cell function could be impaired by the treatment for
      Wilms' tumour (WT) in childhood. We investigated the insulin secretion of 44
      survivors of WT (22 males) with a median off-treatment follow up of 8.3 years
      (range 1-19.8). All patients had an intravenous glucose tolerance test (IVGTT)
      (0.5 gm/kg, max 25 g) to determine the first-phase insulin response (FPIR) (sum
      of the 1- and 3-min insulin concentrations). Median age at the time of the study
      was 12.7 years (range 4.2-22.7). Eight subjects (7 males) had a FPIR value below
      the 3rd percentile, and 7 (3 males) above the 97th centile. Among the 22 patients
      who received radiotherapy. 7 (6 males) showed a FPIR < 3rd percentile versus only
      1 (a male) of the 22 patients who received no radiation (31.8% vs 4.5%; P <
      0.05). Analysis of variance showed that the time elapsed since therapy had a
      significant role on the development of low FPIR only in males. The 7 patients
      with an insulin release > 97th percentile did not show any significant difference
      compared to subjects with lower insulin values for weight, age at diagnosis, sex,
      time elapsed since treatment, radiotherapy and chemotherapy protocol. CONCLUSION:
      An impaired insulin response is evident in some patients treated for WT in
      childhood, mainly in male patients who received abdominal radiotherapy and were
      examined a longer time after therapy. We hypothesize that this decreased insulin
      release is related to damage due to radiotherapy and therefore a careful follow
      up is recommended in adulthood in these patients.

PMID- 9177980
TI  - The effect of obesity, age, puberty and gender on resting metabolic rate in
      children and adolescents.
AB  - During puberty fat-free mass (FFM) and fat mass (FM) change quickly and these
      changes are influenced by sex and obesity. Since it is not completely known how
      these changes affect resting metabolic rate (RMR), the aim of the present study
      was to investigate the effect of body composition, age, sex and pubertal
      development of postabsorptive RMR in 9.5- to 16.5- year-old obese and non-obese
      children. Postabsorptive RMR was measured in a sample of 371 pre- and
      postpubertal children comprising 193 males (116 non-obese and 77 obese) and 178
      females (119 non-obese and 59 obese). RMR was assessed by indirect calorimetry
      using a ventilated hood system for 45 min after an overnight fast. Body
      composition (FFM and FM) was estimated from skinfold measurements. The mean (+/-
      SD) RMR was significantly (P < 0.001) lower in non-obese (males: 5600 +/- 972
      kJ/24 h; females: 5112 +/- 632 kJ/24 h) than in obese (males: 7223 +/- 1220 kJ/24
      h; females: 6665 +/- 1106 kJ/24 h) children. This difference became non
      significant when RMR was adjusted for body composition (FFM+FM). However, the
      difference between the genders still remained significant (control male: 6118 +/-
      507, control female: 5652 +/- 507, P < 0.001; obese male: 6256 +/- 507, obese
      female: 5818 +/- 507 kJ/24 h, P < 0.001). The main determinant of RMR was FFM. In
      the whole cohort. FFM explained 79.8% of the variation in RMR, followed by age,
      gender and FM adding further 3.8%, 1.1% and 0.8% to the predictability of RMR,
      respectively. No significant contribution for study group (obese, non-obese),
      pubertal stage, or fat distribution was found in the regression for RMR. The
      adjusted value of RMR (for FFM and FM) slightly, but significantly (P < 0.01)
      decreased between the age of 10-16 years, demonstrating the important effect of
      age on RMR. CONCLUSIONS: The resting metabolic rate of obese and control children
      is not different when adjusted for body composition. The main determinant of RMR
      is the fat-free mass, however, age, gender and fat mass are also significant
      factors. Pubertal development and fat distribution do not influence RMR
      independently from the changes in body composition.

PMID- 9177981
TI  - A new case of malonyl coenzyme A decarboxylase deficiency presenting with
      cardiomyopathy.
AB  - A new case of mitochondrial malonyl coenzyme A decarboxylase deficiency is
      described. The patient presented with an initial episode of metabolic acidosis,
      seizures, hypoglycemia, and cardiac failure at 2 months of age which slowly
      resolved. Subsequent evaluations at 4 years of age for developmental delay
      revealed a prominent elevation of malonic acid in urine. Malonyl carnitine was
      also elevated. The activity of Malonyl CoA decarboxylase in cultured fibroblasts
      was 7% of normal. CONCLUSION: Malonyl CoA decarboxylase deficiency may result in
      inhibition of fatty acid oxidation, which may account for the cardiomyopathy.

PMID- 9177982
TI  - Early nasal continuous positive airway pressure treatment reduces the need for
      intubation in very low birth weight infants.
AB  - Nasal continuous positive airway pressure (CPAP) applied shortly after birth is
      said to be an effective treatment of respiratory distress in very low birth
      weight infants (VLBW). We tested the hypothesis that the use of early nasal CPAP
      (applied as soon as signs of respiratory distress occurred, usually within 15 min
      after birth) reduces the need for intubation, the duration of intermittent
      mandatory ventilation and the incidence of bronchopulmonary dysplasia. All
      liveborn VLBW infants (birth weight < 1500 g) admitted to our tertiary neonatal
      intensive care unit in 1990 (historical controls) and in 1993 (early nasal CPAP
      group) entered the study. The intubation rate was significantly lower after
      introduction of nasal CPAP (30% vs 53%, P = 0.016). Median duration of intubation
      was 4.5 days (interquartile range 3-7 days) before versus 6.0 days (2.8-9 days)
      after nasal CPAP was introduced (P = 0.73). The incidence of bronchopulmonary
      dysplasia was not reduced significantly (32% vs 30%, P = 0.94). Survival until
      discharge was 89.5%, before versus 92.9% after introduction of nasal CPAP (P =
      0.54). CONCLUSION: Early nasal CPAP is an effective treatment of respiratory
      distress in VLBW infants, significantly reducing the need for intubation and
      intermittent mandatory ventilation, without worsening other standard measures of
      neonatal outcome. We found no significant decrease in the incidence of
      bronchopulmonary dysplasia.

PMID- 9177983
TI  - Neonatal morbidity and mortality associated with maternal haemolysis elevated
      liver enzymes and low platelets syndrome.
AB  - To compare the impact of maternal haemolysis, elevated liver enzymes and low
      platelets (HELLP) syndrome, uncomplicated hypertension in pregnancy (HIP), and no
      hypertension (controls) on neonatal morbidity and mortality, 108 infants were
      matched with respect to gestational age, date of birth, and gender. The HELLP
      group infants had more grade 3 and 4 respiratory distress syndromes (36%) than
      the HIP group (19%) or controls (11%). Cardiovascular instability (arterial
      hypotension, volume resuscitation) was significantly more common in HELLP
      neonates (20% and 31%) than in HIP infants (9% and 6%) or controls (3% and 9%).
      Both, HELLP and HIP infants showed a higher incidence of growth retardation than
      the controls. After 32 weeks of gestation the incidence of severe neonatal
      morbidity was not different. CONCLUSION: : Before 32 weeks of gestation both
      respiratory and cardiovascular morbidity and intra-uterine growth retardation
      associated with HIP is further aggravated by a maternal HELLP syndrome.

PMID- 9177984
TI  - Antenatal ambroxol treatment does not prevent the respiratory distress syndrome
      in premature infants.
AB  - The effectiveness of ambroxol in the prevention of neonatal respiratory distress
      syndrome and in reducing the need for intermittent mandatory ventilation and
      oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34
      weeks of gestation and who were randomized either for treatment with ambroxol
      (group A = 42) or served as control (group B = 46). There were no significant
      differences in the mean gestational age, birth weight or Apgar score between the
      two groups. We found no significant differences in occurrence of respiratory
      distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation
      (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and
      B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol
      treatment both for the prevention of neonatal respiratory distress syndrome and
      for the reduction of its severity.

PMID- 9177985
TI  - Hypertrophic cardiomyopathy in preterm infants treated with dexamethasone.
AB  - Steroid therapy has been widely used in neonates for its beneficial effects.
      Adverse side-effects have been described, also affecting the cardiovascular
      system. We report two cases of hypertrophic cardiomyopathy in two preterm
      newborns secondary to dexamethasone treatment. Full recovery occurred after
      discontinuing steroids. Risk/benefit ratios must be carefully considered before
      using steroids in the neonatal period. CONCLUSION: Serial echocardiographic
      evaluations should be performed to evaluate prevalence and clinical relevance of
      hypertrophic cardiomyopathy in preterm infants treated with dexamethasone.

PMID- 9177986
TI  - Plasma lipid and apolipoprotein concentrations in full term infants fed formula
      supplemented with long-chain polyunsaturated fatty acids and cholesterol.
AB  - Recent data indicate that supplementation of infant formula with omega-3 and
      omega-6 long-chain polyunsaturated fatty acids might offer developmental benefits
      for full term infants. We investigated biochemical consequences of feeding
      formula supplemented with egg lipids to provide long-chain polyunsaturated fatty
      acids and compared triglyceride, cholesterol, lipoprotein cholesterol (HDL2
      cholesterol, HDL3-cholesterol, non-HDL-cholesterol) and apolipoprotein A-I, A-II
      and B concentrations in full term infants fed either conventional formula (n =
      10) or a formula supplemented with omega-3 and omega-6 long-chain polyunsaturated
      fatty acids and cholesterol in amounts similar to those found in mature human
      milk (n = 12). At the age of 5 days, cholesterol, non-HDL-cholesterol and
      triglyceride concentrations were significantly higher in infants fed supplemented
      than in those receiving conventional formula. At the age of 30 days, triglyceride
      concentrations were significantly higher with supplemented than with conventional
      formula. Thereafter throughout the study, no significant differences were seen
      between the two groups. CONCLUSION: Full term infants fed formula supplemented
      with omega-3 and omega-6 long-chain polyunsaturated fatty acids and cholesterol
      showed significantly higher plasma cholesterol and triglyceride concentrations
      than infants receiving conventional formula on day 5 and on days 5 and 30,
      respectively. Thereafter no appreciable effect of diet on plasma phospholipid,
      triglyceride, cholesterol, lipoprotein cholesterol and apolipoprotein
      concentrations were seen.

PMID- 9177987
TI  - A comparison of intratracheal and intravenous administration of gentamicin during
      liquid ventilation.
AB  - Pulmonary absorption of aminoglycosides is poor with intravenous administration,
      but may be enhanced by direct intratracheal administration of these drugs using
      perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin
      sulfate was administered to two groups of newborn lambs during LV. Serum and lung
      tissue levels of gentamicin were compared after either pulmonary intratracheal
      (IT) or intravenous (IV) routes of administration. Serial serum levels of
      gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h,
      and then hourly until sacrifice (maximum 6 h). At sacrifice, representative
      samples of each lung lobe were homogenized and analyzed for tissue gentamicin
      content. At 1 h, serum gentamicin levels were similar in both groups: IT
      administration levels were 3.7 +/- 0.55 SE micrograms/ml and IV levels were 3.5
      +/- 0.85 SE micrograms/ml. The peak serum gentamicin level of 4.8 +/- 0.8 SE
      micrograms/ml for the pulmonary administration group occurred 1.5 h after
      administration. Lung tissue levels of gentamicin for IT administration (4.04 +/-
      0.62 SE micrograms/g) were significantly greater than for IV administration (1.75
      +/- 0.33 SE micrograms/g; P < 0.05). There were no significant differences in
      interlobar gentamicin distribution for either mode of administration. CONCLUSION:
      Perfluorochemical can be used as a vehicle for intratracheal delivery of
      antimicrobials. This route provides equivalent serum levels at 1 h, higher lung
      tissue levels, and uniform interlobar distribution relative to intravenous
      administration of gentamicin. We speculate that pulmonary administered gentamicin
      during LV may provide an effective alternative treatment modality in the
      management of severe neonatal pneumonia.

PMID- 9177988
TI  - Sudden infant death and prevalence of whooping cough in the Swedish and Norwegian
      communities.
AB  - Whooping cough (WC) has been suggested to be a trigger factor for sudden infant
      death (SID), the proposed mechanism being unrecognised hypoxaemic episodes. In
      contrast to Norway, Sweden ceased its immunisation programme against Bordetella
      pertussis (BP) in 1979. We investigated the relation between SID mortality and
      the prevalence of BP during 1983 to 1988, by month, in the two ethnically and
      socially similar, bordering countries adopting different strategies towards WC.
      In addition, the greater Stockholm area was analysed. For both countries the
      prevalence of BP was collected from monthly reports by regional health officers.
      SID mortality rates were provided by the Norwegian Central Bureau of Statistics
      and the SID registry at the Swedish National Board of Health and Welfare. The
      relation between SID mortality rate and prevalence of WC, by month, was analysed
      by linear regression. In addition, the consistency of seasonal fluctuations was
      investigated by analysing the covariance between average, pooled, monthly values
      of the two variables. SID mortality rate followed significantly the monthly
      prevalence of BP in Sweden (P < 0.01) and Stockholm (P < 0.0001) during the study
      period. In Norway there was a significant correlation only during the epidemic
      outbreak of WC (P < 0.05), but not for the whole study period. When controlling
      for seasonality a significant correlation remained in the urban area of Stockholm
      (P < 0.05). CONCLUSION: It is suggested that covariations between WC and SID
      mortality rate may be related to transmission rate and immunisation status of the
      investigated population.

PMID- 9177989
TI  - A retrospective analysis of ingestion of caustic substances by children. Ten-year
      statistics in Galicia.
AB  - We reviewed the case histories of 743 children seen at our hospital from 1981 to
      1990 for suspected ingestion of caustic substances. Mean patient age was 27
      months; 85% of patients were less than 3 years old. The male-to-female ratio was
      about 2:1. About 53% of patients were from urban environments. All ingestions
      appear to have been accidental. Of the 743 children, 20% presented oesophageal
      burns (11.8% first-degree, 3.1% second-degree and 2.7% third-degree). Alkaline
      products were ingested about 11 times more frequently than acid products. The
      substance ingested was bleach in 73% of cases. The most dangerous substances were
      dishwasher liquids/powders (59% of ingestions led to oesophageal burn), caustic
      soda (55%) and drain cleaners (55%). The caustic product was not in its original
      container in 75% of cases. Most accidents (58%) took place in the home. We did
      not detect any reliable predictive relationship between the presence of symptoms
      and signs and of oesophageal burns. Of the 743 patients, 5% developed oesophageal
      stricture and 3% required oesophageal dilatation. CONCLUSION: The incidence of
      accidents caused by the ingestion of caustic substances can only be reduced by
      broad-based preventive strategies, including enforcement of safe manufacturing
      practices and public education programmes. Most importantly, the containers for
      caustic household products should be cheap, small and childproof.

PMID- 9177990
TI  - Case of the month: a five-year-old girl with intractable arthralgias.

PMID- 9177991
TI  - Reaction of term newborns with prolonged postnatal dyspnoea to early oxygen, mask
      CPAP and volume expansion: a prospective randomized clinical trial.

PMID- 9177992
TI  - A warning for the treatment of hyperkalaemia with salbutamol.

PMID- 9177993
TI  - Hepatitis B and C infection in children with Down syndrome.

PMID- 9177994
TI  - Hypomagnesaemia-associated tetany due to intravenous administration of
      amphotericin B.

PMID- 9177995
TI  - MutS, proofreading and cancer.

PMID- 9177996
TI  - Transduction of low-copy number plasmids by bacteriophage P22.
AB  - The generalized transducing bacteriophage of Salmonella typhimurium, P22, can
      transduce plasmids in addition to chromosomal markers. Previous studies have
      concentrated on transduction of pBR322 by P22 and P22HT, the high transducing
      mutant of P22. This study investigates the mechanism of P22HT transduction of low
      copy number plasmids, namely pSC101 derivatives. We show that P22HT transduces
      pSC101 derivatives that share homology with the chromosome by two distinct
      mechanisms. In the first mechanism, the plasmid integrates into the chromosome of
      the donor by homologous recombination. This chromosomal fragment is then packaged
      in the transducing particle. The second mechanism is a size-dependent mechanism
      involving a putative plasmid multimer. We propose that this multimer is formed by
      interplasmidic recombination. In contrast, P22HT can efficiently transduce pBR322
      by a third mechanism, which is independent of plasmid homology with the
      chromosome. It has been proposed that the phage packages a linear concatemer
      created during rolling circle replication of pBR322, similar in fashion to phage
      genome packaging. This study investigates the role of RecA, RecD, and RecF
      recombination proteins in plasmid/plasmid and plasmid/chromosome interactions
      that form packageable substrates in the donor. We also examine the resolution of
      various transduced plasmid species in the recipient and the roles of RecA and
      RecD in these processes.

PMID- 9177997
TI  - Enhanced deletion formation by aberrant DNA replication in Escherichia coli.
AB  - Repeated genes and sequences are prone to genetic rearrangements including
      deletions. We have investigated deletion formation in Escherichia coli strains
      mutant for various replication functions. Deletion was selected between 787 base
      pair tandem repeats carried either on a ColE1-derived plasmid or on the E. coli
      chromosome. Only mutations in functions associated with DNA Polymerase III
      elevated deletion rates in our assays. Especially large increases were observed
      in strains mutant in dnaQ the epsilon editing subunit of Pol III, and dnaB, the
      replication fork helicase. Mutations in several other functions also altered
      deletion formation: the alpha polymerase (dnal;), the gamma clamp loader complex
      (holC, dnaX), and the beta clamp (dnaN) subunits of Pol III and the primosomal
      proteins, dnaC and priA. Aberrant replication stimulated deletions through
      several pathways. Whereas the elevation in dnaB strains was mostly recA- and lexA
      dependent, that in dnaQ strains was mostly recA- and lexA-independent. Deletion
      product analysis suggested that slipped mispairing, producing monomeric replicon
      products, may be preferentially increased in a dnaQ mutant and sister-strand
      exchange, producing dimeric replicon products, may be elevated in dnaE mutants.
      We conclude that aberrant Polymerase III replication can stimulate deletion
      events through several mechanisms of deletion and via both recA-dependent and
      independent pathways.

PMID- 9177998
TI  - Long-term experimental evolution in Escherichia coli. VI. Environmental
      constraints on adaptation and divergence.
AB  - The effect of environment on adaptation and divergence was examined in two sets
      of populations of Escherichia coli selected for 1000 generations in either
      maltose-or glucose-limited media. Twelve replicate populations selected in
      maltose-limited medium improved in fitness in the selected environment, by an
      average of 22.5%. Statistically significant among-population genetic variation
      for fitness was observed during the course of the propagation, but this variation
      was small relative to the fitness improvement. Mean fitness in a novel nutrient
      environment, glucose-limited medium, improved to the same extent as in the
      selected environment, with no statistically significant among-population genetic
      variation. In contrast, 12 replicate populations previously selected for 1000
      generations in glucose-limited medium showed no improvement, as a group, in
      fitness in maltose-limited medium and substantial genetic variation. This
      asymmetric pattern of correlated responses suggests that small changes in the
      environment can have profound effects on adaptation and divergence.

PMID- 9177999
TI  - Recombination and the progression of meiosis in Saccharomyces cerevisiae.
AB  - Recombination is an essential part of meiosis: in almost all organisms, including
      Saccharomyces cerevisiae, proper chromosome segregation and the viability of
      meiotic products is dependent upon normal levels of recombination. In this
      article we examine the kinetics of the meiotic divisions in four mutants
      defective in the initiation of recombination. We find that mutations in any of
      three Early Exchange genes (REC104, REC114 or REC102) confer a phenotype in which
      the reductional division occurs earlier than in an isogenic wild-type diploid. We
      also present data confirming previous reports that strains with a mutation in the
      Early Exchange gene. MEI4 undergo the first division at about the same time as
      wild-type cells. The rec104 mutation is epistatic to the mei4 mutation for the
      timing of the first division. These observations suggest a possible relationship
      between the initiation of recombination and the timing of the reductional
      division. These data also allow these four Early Exchange genes examined to be
      distinguished in terms of their role in coordinating recombination with the
      reductional division.

PMID- 9178000
TI  - Stabilization of microsatellite sequences by variant repeats in the yeast
      Saccharomyces cerevisiae.
AB  - We examined the effect of a single variant repeat on the stability of a 51-base
      pair (bp) microsatellite (poly GT). We found that the insertion stabilizes the
      microsatellite about fivefold in wild-type strains. The stabilizing effect of the
      variant base was also observed in strains with mutations in the DNA mismatch
      repair genes pms1, msh2 and msh3, indicating that this effect does not require a
      functional DNA mismatch repair system. Most of the microsatellite alterations in
      the pms1, msh2 and msh3 strains were additions or deletions of single GT repeats,
      but about half of the alterations in the wild-type and msh6 strains were large (>
      8 bp) deletions or additions.

PMID- 9178001
TI  - rco-3, a gene involved in glucose transport and conidiation in Neurospora crassa.
AB  - Macroconidiation in Neurospora crassa is influenced by a number of environmental
      cues, including the nutritional status of the growing organism. Conidia formation
      is normally observed when the fungus is exposed to air. However, carbon
      limitation can induce conidiation in mycclia submerged in an aerated liquid
      medium. A mutant was previously isolated that could conidiate in submerged
      culture without imposing nutrient limitation and the gene responsible for this
      phenotype (rco-3) has now been cloned. RCO3 exhibits sequence similarity to
      members of the sugar transporter gene superfamily, with greatest similarity to
      glucose transporters of yeast. Consistent with this structural similarity, we
      find that glucose transport activity is altered in the mutant. However, growth of
      the mutant in media containing alternate carbon sources does not suppress
      conidiation in submerged culture. The properties of the mutant suggest that RCO3
      is required for expression of glucose transport activity, glucose regulation of
      gene expression, and general carbon repression of development.

PMID- 9178002
TI  - Cytosine methylation associated with repeat-induced point mutation causes
      epigenetic gene silencing in Neurospora crassa.
AB  - Repeated DNA sequences are frequently mutated during the sexual cycle in
      Neurospora crassa by a process named repeat-induced point mutation (RIP). RIP is
      often associated with methylation of cytosine residues in and around the mutated
      sequences. Here we demonstrate that this methylation can silence a gene located
      in nearby, unique sequences. A large proportion of strains that had undergone RIP
      of a linked duplication flanking a single-copy transgene, hph (hygromycin B
      phosphotransferase), showed partial silencing of hph. These strains were all
      heavily methylated throughout the single-copy hph sequences and the flanking
      sequences. Silencing was alleviated by preventing methylation, either by 5
      azacytidine (5AC) treatment or by introduction of a mutation (eth-I) known to
      reduce intracellular levels of S-adenosylmethionine. Silenced strains exhibited
      spontaneous reactivation of hph at frequencies of 10(4) to 0.5. Reactivated
      strains, as well as cells that were treated with 5AC, gave rise to cultures that
      were hypomethylated and partially hygromycin resistant, indicating that some of
      the original methylation was propagated by a maintenance mechanism. Gene
      expression levels were found to be variable within a population of clonally
      related cells, and this variation was correlated with epigenetically propagated
      differences in methylation patterns.

PMID- 9178003
TI  - Isolation and characterization of a temperature-sensitive circadian clock mutant
      of Neurospora crassa.
AB  - A new circadian clock mutant has been isolated in Neurospora crassa. This new
      mutation, called period-6 (prd-6), has two features novel to known clock
      mutations. First, the mutation is temperature sensitive. At restrictive
      temperatures (above 21 degrees) the mutation shortens circadian period length
      from a wild-type value of 21.5 hr to 18 hr. At permissive temperatures (below 21
      degrees) the mutant has a 20.5-hr period length close to that of the wild-type
      strain. Second, the prd-6 mutation is epistatic to the previously isolated clock
      mutation period-2 (prd-2). This epistasis is unusual in that the prd-2 prd-6
      double mutant strain has an 18-hr period length at both the restrictive and
      permissive temperatures. That is, the temperature-sensitive aspect of the
      phenotype of the prd-6 strain is lost in the prd-2 prd-6 double mutant strain.
      This suggests that the gene products of the prd-2 and prd-6 loci may interact
      physically and that the presence of a normal prd-2+ protein is required for low
      temperature to "rescue" the prd-6 mutant phenotype. These results, combined with
      our recent finding that prd-2 and some alleles of the frq gene show genetic
      synergy, suggest that it may be possible to establish a more comprehensive model
      of the Neurospora circadian clock.

PMID- 9178004
TI  - A putative rhamnogalacturonase required for sexual development of Neurospora
      crassa.
AB  - In previous work, the asd-I (ascus development) gene of the filamentous fingus
      Neurospora crassa was identified as a gene expressed preferentially during the
      sexual cycle and shown to be essential for normal sexual development. The asd-I
      gene has been sequenced and further characterized. It contains two introns, the
      first of which is in-frame and inefficiently or differentially spliced. The
      predicted ASD-I protein has extensive homology with rhamnogalacturonase B of
      Aspergillus aculeatus, which cleaves the backbone within the ramified hairy
      regions of pectin. In homozygous asd-I crosses, sexual development is initiated
      and large numbers of normal-sized asci are formed. Ascospore delineation does not
      occur, however, and no sexual progeny are produced. As most asd-I asci contain
      eight nuclei, the two meiotic divisions and subsequent mitotic division typical
      of normal crosses seem to occur, but the haploid nuclei are not partitioned into
      ascospores. In wild-type crosses, the ASD-I protein is present in large amounts
      in croziers and young asci, but it is only faintly detectable in more mature asci
      containing developing ascospores. Models to explain the possible role of a
      rhamnogalacturonase in sexual development are presented.

PMID- 9178005
TI  - Multiple genes encoding pheromones and a pheromone receptor define the B beta 1
      mating-type specificity in Schizophyllum commune.
AB  - The genes defining multiple B mating types in the wood-rotting mushroom
      Schizophyllum commune are predicted to encode multiple pheromones and pheromone
      receptors. These genes are clustered in each of two recombinable and
      independently functioning loci, B alpha and B beta. A difference in specificity
      at either locus between a mated pair of individuals initiates an identical series
      of events in sexual morphogenesis. The B alpha 1 locus was recently found to
      contain genes predicted to encode three lipopeptide pheromones and a pheromone
      receptor with a seven-transmembrane domain. These gene products interact in
      hetero-specific pairs, the pheromone of one B alpha specificity with the receptor
      of any one of the other eight B alpha specificities, and are likely to activate a
      signaling cascade similar to that known for mating in Saccharomyces cerevisiae.
      We report here that the B beta 1 locus also contains at least three pheromone
      genes and one pheromone receptor gene, which function similarly to the genes in
      the B alpha 1 locus, but only within the series of B beta specificities. A
      comparison of the DNA sequences of the B alpha 1 and B beta 1 loci suggests that
      each arose from a common ancestral sequence, allowing us to speculate about the
      evolution of this unique series of regulatory genes.

PMID- 9178006
TI  - Mechanism of activation of the Caenorhabditis elegans ras homologue let-60 by a
      novel, temperature-sensitive, gain-of-function mutation.
AB  - The Caenorhabditis elegans let-60 gene encodes a Ras protein that mediates
      induction of the hermaphrodite vulva. To better understand how mutations
      constitutively activate Ras and cause unregulated cell division, we have
      characterized ga89, a temperature-sensitive, gain-of-function mutation in let-60
      ras. At 25 degrees, ga89 increases let-60 activity resulting in a multivulva
      phenotype. At 15 degrees, ga89 decreases let-60 activity resulting in a vulvaless
      phenotype in let-60(ga89)/Df animals. The ga89 mutation causes a leucine (L) to
      phenylalanine (F) substitution at amino acid 19, a residue conserved in all Ras
      proteins. We introduced the L19F change into human H-Ras protein and found that
      the in vitro GTPase activity of H-Ras became temperature-dependent. Genetic
      experiments suggest that LET-60 (L19F) interacts with GAP and GNEF, since
      mutations that decrease GAP and GNEF activity affect the multivulva phenotype of
      let-60(ga89) animals. These results suggest that the L19F mutation primarily
      affects the intrinsic rate of GTP hydrolysis by Ras, and that this effect may be
      sufficient to account for the activated-Ras phenotype caused by let-60(ga89). Our
      results suggest that a mutation in a human ras gene analogous to ga89 might
      contribute to oncogenic transformation.

PMID- 9178007
TI  - The Caenorhabditis elegans spe-5 gene is required for morphogenesis of a sperm
      specific organelle and is associated with an inherent cold-sensitive phenotype.
AB  - The nonrandom segregation of organelles to the appropriate compartment during
      asymmetric cellular division is observed in many developing systems.
      Caenorhabditis elegans spermatogenesis is an excellent system to address this
      issue genetically. The proper progression of spermatogenesis requires specialized
      intracellular organelles, the fibrous body-membranous organelle complexes (FB
      MOs). The FB-MOs play a critical role in cytoplasmic partitioning during the
      asymmetric cellular division associated with sperm meiosis II. Here we show that
      spe-5 mutants contain defective, vacuolated FB-MOs and usually arrest
      spermatogenesis at the spermatocyte stage. Occasionally, spe-5 mutants containing
      defective FB-MOs will form spermatids that are capable of differentiating into
      functional spermatozoa. These spe-5 spermatids exhibit an incomplete penetrance
      for tubulin mis-segregation during the second meiotic division. In addition to
      morphological and FB-MO segregation defects, all six spe-5 mutants are cold
      sensitive, exhibiting a more penetrant sterile phenotype at 16 degrees than 25
      degrees. This cold sensitivity could be an inherent property of FB-MO
      morphogenesis.

PMID- 9178008
TI  - Insertions of hybrid P elements in the yellow gene of Drosophila cause a large
      variety of mutant phenotypes.
AB  - A series of yellow mutations associated with a great variety of tissue-specific
      phenotypes were obtained from several highly unstable Drosophila melanogaster
      strains carrying the gypsy-induced y2 allele. These mutations are caused by
      insertion of additional DNA sequences of variable size 69 bp upstream of the
      yellow transcription start site. These sequences are flanked by identical copies
      of a deleted 1.2-kb P element arranged in the same or inverted orientation. The
      central part of the inserted element consists of genomic sequences originating
      from different regions of the X chromosome. The mutant phenotype caused by these
      chimeric elements depends on the nature of the sequences present either in the P
      element or in the central part of the insertion, suggesting that these sequences
      are able to affect expression of the yellow gene. In addition, sequences present
      in the central region of the insertions strongly modify the effects of the gypsy
      bound suppressor of Hairy-wing [su(Hw)] and modifier of mdg4 [mod(mdg4)] proteins
      on yellow transcription. Analyses of these mutations give new insights into the
      mechanisms by which su (Hw) and mod(mdg4) affect enhancer function.

PMID- 9178009
TI  - The CRE-binding protein dCREB-A is required for Drosophila embryonic development.
AB  - We have previously described the cloning of a cyclic AMP response-element (CRE)
      binding protein, dCREB-A, in Drosophila melanogaster that is similar to the
      mammalian CRE-binding protein CREB. dCREB-A is a member of the bZIP family of
      transcription factors, shows specific binding to the (CRE), and can activate
      transcription in cell culture. In this report, we describe the gene structure for
      dCREB-A, protein expression patterns throughout development and the necessary
      role for this gene in embryogenesis. The 4.5-kb transcript is encoded in six
      exons that are distributed over 21 kb of DNA. There are seven start sites and no
      TATA consensus sequences upstream. The dCREB-A protein is expressed in the nuclei
      of the embryonic salivary gland, proventriculus and stomadeum. Late in
      embryogenesis, tracheal cell nuclei and specific nuclei within the segments show
      staining with anti-dCREB-A antibodies. In adult female ovaries, dCREB-A is
      expressed in the stage 9 through stage 11 follicle cell nuclei. Null mutations of
      the dCREB-A gene give rise to animals that no longer express dCREB-A protein and
      die late in embryogenesis before or at hatching. The absolute requirement of
      dCREB-A for embryogenesis demonstrates a nonredundant function for a CRE-binding
      protein that will be useful in studying the role of specific signal transduction
      cascades in development.

PMID- 9178010
TI  - Genetic and molecular analysis of smooth, a quantitative trait locus affecting
      bristle number in Drosophila melanogaster.
AB  - A semi-lethal, sterile allele of the smooth locus (2-91.5), sm3, was discovered
      in an artificial selection line for low abdominal bristle number that had been
      started from a P-M dysgenic cross. The fitness effects and extremely low bristle
      number phenotype of the allele could not be separated by recombination from a P
      element insertion at cytological location 56E, and precise excision of the P
      element at this site was associated with reversion to wild type. The smooth gene
      was cloned using the P-element insertion as a tag. The gene encodes a 2.6-kb
      transcript derived from 10 exons and covers a genomic region of at least 80 kb.
      The Drosophila smooth gene shares substantial sequence identity with a group of
      RNA binding proteins, with the closest relationship being to the human
      heterogeneous nuclear ribonucleoprotein L gene. The smooth gene is by definition
      an abdominal bristle number quantitative trait locus, but further work is
      required to discern whether naturally occurring allelic variation at this locus
      is a source of genetic variation for abdominal bristle number in natural
      populations.

PMID- 9178011
TI  - Ras1-mediated modulation of Drosophila homeotic function in cell and segment
      identity.
AB  - Mutations of the Drosophila homeotic proboscipedia gene (pb, the Hox-A2/B2
      homologue) provoke dose-sensitive defects. These were used to search for dose
      sensitive dominant modifiers of pb function. Two identified interacting genes
      were the proto-oncogene Ras1 and its functional antagonist Gap1, prominent
      intermediaries in known signal transduction pathways. Ras1+ is a positive
      modifier of pb activity both in normal and ectopic cell contexts, while the Ras1
      antagonist Gap1 has an opposite effect. A general role for Ras1 in homeotic
      function is likely, since Ras1+ activity also modulates functions of the homeotic
      loci Sex combs reduced and Ultrabithorax. Our data suggest that the modulation
      occurs by a mechanism independent of transcriptional control of the homeotic loci
      themselves, or of the Ras1/Gap1 genes. Taken together our data support a role for
      Ras1-mediated cell signaling in the homeotic control of segmental
      differentiation.

PMID- 9178012
TI  - Altering developmental trajectories in mice by restricted index selection.
AB  - A restricted index selection experiment on mice was carried out for 1-4
      generations on rate of early postnatal development (growth rate from birth to 10
      days of age) vs. rate of development much later in ontogeny (growth rate from 28
      to 56 days of age). Early rate of development (E) approximates hyperplasia
      (changes in cell number) and later rate (L) reflects hypertropy (changes in cell
      size). The selection criteria were as follows; E+LO was selected to increase
      early body weight gain while holding late body weight gain constant; E-LO was
      selected to decrease early body gain while holding late gain constant; EOL+ was
      selected to increase late gain holding early gain constant; and EOL- was selected
      to decrease late gain holding early gain constant. After 14 generations of
      selection, significant divergence among lines has occurred and the changes in the
      growth trajectories are very close to expectation. The genetic and developmental
      bases of complex traits are discussed as well as the concept of developmental
      homoplasy.

PMID- 9178013
TI  - Recombination creates novel L1 (LINE-1) elements in Rattus norvegicus.
AB  - Mammalian L1 (long interspersed repeated DNA. LINE-1) retrotransposons consist of
      a 5' untranslated region (UTR) with regulatory properties, two protein encoding
      regions (ORF I, ORF II, which encodes a reverse transcriptase) and a 3' UTR. L1
      elements have been evolving in mammals for > 100 million years and this process
      continues to generate novel L1 subfamilies in modern species. Here we
      characterized the youngest known subfamily in Rattus norvegicus, L1mlvi2, and
      unexpectedly found that this element has a dual ancestry. While its 3' UTR shares
      the same lineage as its nearest chronologically antecedent subfamilies, L13 and
      L14, its ORF I sequence does not. The L1mlvi2 ORF I was derived from an ancestral
      ORF I sequence that was the evolutionary precursor of the L13 and L14 ORF I. We
      suggest that an ancestral ORF I sequence was recruited into the modern L1mlvi2
      subfamily by recombination that possibly could have resulted from template strand
      switching by the reverse transcriptase during L1 replication. This mechanism
      could also account for some of the structural features of rodent L1 5' UTR and
      ORF I sequences including one of the more dramatic features of L1 evolution in
      mammals, namely the repeated acquisition of novel 5' UTRs.

PMID- 9178014
TI  - Ancestral polymorphism of Mhc class II genes in mice: implications for balancing
      selection and the mammalian molecular clock.
AB  - To investigate the evolutionary dynamics at Mhc class II DR genes of mice (genus
      Mus), we sequenced the peptide binding regions (PBRs) of 41 DRB (= E beta) genes
      and eight DRA (= E alpha) genes from 15 strains representing eight species. As
      expected trees of these PBR sequences imply extensive maintenance of ancestral
      DRB alleles across species. We use a coalescent simulation model to show that the
      number of interspecific coalescent events (c) observed on these trees was higher
      than the number expected for neutral genealogies and similar sample sizes and is
      more consistent with balancing selection that with neutrality. Patterns of
      ancestral polymorphism in mouse DRB alleles were also used to examine the tempo
      of synonymous substitution in the PBR of mouse class II genes. Both absolute and
      relative rate tests on DRA and DRB genes imply increased substitution rates at
      two- and fourfold degenerate sites of mice and rats relative to primates, and
      decreased rates for the DRB genes of primates relative to ungulate and carnivore
      relatives. Thus rates of synonymous substitution at Mhc DR genes in mammals
      appear to be subject to generation time effects in ways similar to those found at
      other mammalian genes.

PMID- 9178015
TI  - Morph-specific proteins in pollen and styles of distylous turnera (Turneraceae).
AB  - We used nondenaturing isoelectric focusing (IEF) in a survey of plants from 11
      populations to identify style and pollen proteins unique to the short-styled
      morph of Turnera scabra, T. sulnitata and T. krapovickasii. Three protein bands
      [approximately isoelectric points (pls) 6.1, 6.3 and 6.5] were found only in
      styles and stigmas of short-styled plants while two bands (approximately pls 6.7
      and 6.8, M(r) 56 and 59 kD) occur only in pollen of short-styled plants. Some of
      these bands appear very late in development, within 24 hr before flowering. Two
      isozyme loci were mapped to an 8.7 cM region spanning the distyly locus. Using
      these isozyme markers we identified progeny exhibiting recombination adjacent to
      the distyly locus. No recombinants between the distyly locus and the locus or
      loci controlling the presence of the short-styled morph-specific proteins were
      obtained. This suggest that the loci encoding these proteins are either extremely
      tightly linked to the distyly locus and in complete disequilibrium with the S
      allele or exhibit morph-limited expression. Crosses to a plant showing an unusual
      style protein phenotype demonstrated that an additional unlinked locus is
      required for full expression of the style proteins. The function of the morph
      specific proteins is unknown.

PMID- 9178016
TI  - Insertions of a novel class of transposable elements with a strong target site
      preference at the r locus of maize.
AB  - The r locus of maize regulates anthocyanin synthesis in various tissues of maize
      through the production of helix-loop-helix DNA binding proteins capable of
      inducing expression of structural genes in the anthocyanin biosynthetic pathway.
      The complex r variant, R-r: standard (R.r), undergoes frequent mutation through a
      variety of mechanisms including displaced synapsis and crossing over, and
      intrachromosomal recombination. Here we report a new mechanism for mutation at
      the R-r complex: insertion of a novel family of transposable elements. Because
      the elements were first identified in the R-p gene of the R-r complex, they have
      been named P instability Factor (PIF). Two different PIF elements were cloned and
      found to have identical sequences at their termini but divergent internal
      sequences. In addition, the PIF elements showed a marked specificity of insertion
      sites. Six out of seven PIF-containing derivatives examined had an element
      inserted at an identical location. Two different members of the PIF element
      family were identified at this position. The seventh PIF-containing derivative
      examined had the element inserted at a distinct position within r. Even at this
      location, however, the element inserted into a conserved target sequence. The
      timing of PIF excision is unusual. Germinal excision rates can range up to
      several percent of progeny. Yet somatic sectors are rare, even in lines
      exhibiting high germinal reversion rates.

PMID- 9178017
TI  - Recombination and gene flux caused by gene conversion and crossing over in
      inversion heterokaryotypes.
AB  - A theoretical analysis of the effects of inversions on recombination and gene
      flux between arrangements caused by gene conversion and crossing over was carried
      out. Two different mathematical models of recombination were used: the Poisson
      model (without interference) and the Counting model (with interference). The main
      results are as follows. (1) Recombination and gene flux are highly site-dependent
      both inside and outside the inverted regions. (2) Crossing over overwhelms gene
      conversion as a cause of gene flux in large inversions, while conversion becomes
      relatively significant in short inversions and in regions around the breakpoints.
      (3) Under the Counting model the recombination rate between two markers depends
      strongly on the position of the markers along the inverted segment. Two equally
      spaced markers in the central part of the inverted segment have less
      recombination than if they are in a more extreme position. (4) Inversions affect
      recombination rates in the univerted regions of the chromosome. Recombination
      increases in the distal segment and decreases in the proximal segment. These
      results provide an explanation for a number of observations reported in the
      literature. Because inversions are ubiquitous in the evolutionary history of many
      Drosophila species, the effects of inversions on recombination are expected to
      influence DNA variation patterns.

PMID- 9178018
TI  - A likelihood approach to populations samples of microsatellite alleles.
AB  - This paper presents a likelihood approach to population samples of microsatellite
      alleles. A Markov chain recursion method previously published by GRIFFITHS and
      TAVARE is applied to estimate the likelihood function under different models of
      microsatellite evolution. The method presented can be applied to estimate a
      fundamental population genetics parameter theta as well as parameters of the
      mutational model. The new likelihood estimator provides a better estimator of
      theta in terms of the mean square error than previous approaches. Furthermore, it
      is demonstrated how the method may easily be applied to test models of
      microsatellite evolution. In particular it is shown how to compare a one-step
      model of microsatellite evolution to a multi-step model by a likelihood ratio
      test.

PMID- 9178019
TI  - Conditions for protected inversion polymorphism under supergene selection.
AB  - Conditions for protected inversion polymorphism under the operation of both
      karyotype and supergene selection in a viability model have been analytically
      determined. When supergene selection (the effect of recombination in
      homokaryotypes lowering the mean fitness of their offspring) is acting on gene
      arrangements and there is no karyotype selection, it is demonstrated that a
      polymorphic stable equilibrium is reached by the population, which is a function
      of only the recombination effects in homokaryotypes. Under both supergene and
      karyotype selection the degree of dominance (h) of karyotype selection is
      critical to produce a protected inversion polymorphism. In general, the
      opportunity for protected polymorphism increases as the degree of dominance
      decreases. For small s values, the conditions for protected polymorphism are r >
      2sh and c > 2s(h-1), where r and c are the average loss of viability for
      offspring of ST/ST and IN/IN homokaryotypes, respectively. These findings suggest
      that supergene selection may be an important balancing mechanism contributing to
      the maintenance of inversion polymorphism.

PMID- 9178020
TI  - The probability of fixation in populations of changing size.
AB  - The rate of adaptive evolution of a population ultimately depends on the rate of
      incorporation of beneficial mutations. Even beneficial mutations may, however, be
      lost from a population since mutant individuals may, by chance, fail to
      reproduce. In this paper, we calculate the probability of fixation of beneficial
      mutations that occur in populations of changing size. We examine a number of
      demographic models, including a population whose size changes once, a population
      experiencing exponential growth or decline, one that is experiencing logistic
      growth or decline, and a population that fluctuates in size. The results are
      based on a branching process model but are shown to be approximate solutions to
      the diffusion equation describing changes in the probability of fixation over
      time. Using the diffusion equation, the probability of fixation of deleterious
      alleles can also be determined for populations that are changing in size. The
      results developed in this paper can be used to estimate the fixation flux,
      defined as the rate at which beneficial alleles fix within a population. The
      fixation flux measures the rate of adaptive evolution of a population and, as we
      shall see, depends strongly on changes that occur in population size.

PMID- 9178022
TI  - Time trends in obesity: an epidemiological perspective.
AB  - The average prevalence of obesity (BMI > 30 kg/m2) among European centers
      participating in the WHO-MONICA study between 1983 and 1986 was about 15% in men
      and 22% in women Prevalence figures ranged in men from 7% in Gothenburg and 22%
      in Lithuania and in women from 9% to 45% in the same places. Some monitoring
      projects or repeated surveys suggest that the prevalence of obesity has been
      increasing during the past 15 years in some European countries. A closer look at
      data from The Netherlands suggest that average weight increase in the order of
      about 1 kilo can be responsible for quite dramatic increases in the prevalence of
      obesity. This suggest that only small changes in the daily caloric balance may be
      sufficient to increase the number of obese subjects in populations. In The
      Netherlands a decrease in energy intake and fat consumption was observed between
      1987 and 1993 and smoking rates remained relatively stable. This could imply that
      reductions in energy expenditure are the main factors responsible for the
      increase in the prevalence of obesity. Since the increase in the prevalence of
      obesity seems to occur particularly in younger age-groups, the consequences of
      the increase in the prevalence of obesity only become apparent many years later.
      Especially chronic conditions such as arthritis or conditions related to obesity
      but occurring later in life such as cerebrovascular accidents, chronic heart
      failure or breast cancer in women. The rising prevalence of non-insulin dependent
      diabetes mellitus may be one of the first signs of the increasing problem of
      obesity in European countries.

PMID- 9178021
TI  - Mapping-linked quantitative trait loci using Bayesian analysis and Markov chain
      Monte Carlo algorithms.
AB  - A Bayesian method for mapping linked quantitative trait loci (QTL) using multiple
      linked genetic markers is presented. Parameter estimation and hypothesis testing
      was implemented via Markov chain Monte Carlo (MCMC) algorithms. Parameters
      included were allele frequencies and substitution effects for two biallelic QTL,
      map positions of the QTL, and markers, allele frequencies of the markers, and
      polygenic and residual variances. Missing data were polygenic effects and multi
      locus marker-QTL genotypes. Three different MCMC schemes for testing the presence
      of a single or two linked QTL on the chromosome were compared. The first approach
      includes a model indicator variable representing two unlinked QTL, affecting the
      trait, one linked and one unlinked QTL, or both QTL linked with the markers. The
      second approach incorporates an indicator variable for each QTL into the model
      for phenotype, allowing or not allowing for a substitution effect of a QTL, on
      phenotype, and the third approach is based on model determination by reversible
      jump MCMC. Methods were evaluated empirically by analyzing simulated
      granddaughter designs. All methods identified correctly a second, linked QTL and
      did not reject the one-QTL model when there was only a single QTL, and no
      additional or an unlinked QTL.

PMID- 9178023
TI  - Hormonal influence on lipid-protein interactions in biological membranes.
      Lactation effects on alkaline phosphatase activity and intestinal brush border
      membrane properties in rat.
AB  - It is known that prolactin modifies the fluidity of different biological
      membranes in rats and that the activity of intestinal alkaline phosphatase varies
      directly with the fluidity of the membranes in which it is found. Our objective
      was to study the intestinal alkaline phosphatase (IAP) activity, lipid
      composition and fluidity of the proximal small intestine brush border membranes
      under the influence of physiological high levels of prolactin, in rats with 15
      days of lactating (Dams 15 days) compared with control virgin rats. The
      phenomenon was corroborated in dams from which the suckling pups had been
      withdrawn on the tenth day of lactation (Dams 10 days). The results showed a
      decrease on the IAP activity in dams in lactation with relation to control virgin
      and dams with withdrawal of pups. We found decreases in total phospholipids
      contents and fluidity and an increase in the microviscosity lipid membrane in
      dams with 15 days of lactating compared to virgins. In the same groups there were
      no differences in total lipids content and no modifications were observed in the
      quantity of total cholesterol and proteins. These results suggest that the
      changes produced by lactation could be one of the causes of alteration of brush
      border membranes properties by modifying the lipid-protein interactions and the
      alkaline phosphatase activity in the proximal small intestine.

PMID- 9178024
TI  - The lipolytic effects of thyrotropin and isoprenaline are not affected by growth
      hormone in infant adipocytes.
AB  - The lipolytic effects of growth hormone (GH) in children are not fully clarified.
      In this study, no lipolytic effect of GH on isolated adipocytes obtained at
      surgery on healthy infants aged 2-5 months and children 3-6 years was observed.
      Furthermore, GH did not enhance isoprenaline-induced lipolysis, as in adults. The
      TSH-induced lipolysis which is prominent in neonatal adipocytes was not affected
      by incubation of adipocytes with GH. Assuming that GH alters adipocyte metabolism
      primarily by increasing the sensitivity, but not the maximum response, of the
      beta 2-adrenergic receptor population, it follows that GH, in this sense, should
      be a less important co-actor in children where beta 2-adrenergic receptors are
      more abundant.

PMID- 9178025
TI  - Increased in vitro interleukin-12 production by peripheral blood in high-risk
      IDDM first degree relatives.
AB  - Cytokines secreted by antigen presenting cells, lymphocytes T and pancreatic beta
      cells are considered as the major mediators in the pathogenesis of IDDM. It has
      been suggested that cytokines released by macrophages/monocytes could have an
      initial role in beta-cell damage. The aim of the present study was the estimation
      of in vitro production of macrophage-derived cytokines: IL-1 beta, TNF-alpha, IL
      12 by peripheral blood in high risk IDDM first degree relatives, since it could
      reflect early events leading to the development of type 1 diabetes in humans. The
      study was performed in 25 high risk IDDM subjects and 21 age and sex-matched
      healthy controls. IL-1 beta, TNF-alpha and IL-12 concentrations in supernatants
      of whole blood cultures with PHA (10 micrograms/ml) were quantified by ELISA. In
      the ICA positive relatives of IDDM subjects levels of IL-12 were significantly
      higher as compared with the control group, both at 48 h (p < 0.02) and at 72 h (p
      < 0.05) of incubation and positively correlated with TNF-alpha and IL-1 beta (R =
      0.46, p < 0.02 and R = 0.32, p < 0.05). We did not observe statistical
      differences in in vitro production of TNF-alpha and IL-1 beta between the study
      groups. In conclusion we suggest that our findings support the hypothesis, that
      IL-12 is involved in the pathogenesis of human IDDM. If the involvement of Th1
      cells is confirmed in the destruction of islet beta-cells, it is possible that IL
      12 antagonists will have a role in the future prevention of insulin dependent
      diabetes mellitus.

PMID- 9178026
TI  - Predictors of change in insulin sensitivity during glucocorticoid treatment.
AB  - Glucocorticoid induced alterations in carbohydrate metabolism can result in
      hyperglycemia. We evaluated changes in carbohydrate metabolism produced by four
      days of prednisone (20 mg PO TID) measuring insulin sensitivity, basal glucose,
      basal insulin and first phase insulin release (FPIR). We correlated these
      measures of carbohydrate metabolism with changes in free fatty acids and lactate
      levels both of which have been reported to be possible mediators of insulin
      sensitivity. Insulin sensitivity decreased by 64% (p = 0.002), basal insulin
      levels increased 50% (p = 0.026), FPIR tripled (p = 0.064) while fasting glucose
      levels increased significantly but remained normal. Basal FFAs levels increased
      (p = 0.045) while lactate levels did not change significantly, and neither
      predicted changes in SI. Basal levels of SI and FPIR were found to be independent
      predictors of change in insulin sensitivity and together explained 83% of the
      change in insulin sensitivity produced by short term treatment with prednisone.

PMID- 9178027
TI  - Cholesterol 7 alpha-hydroxylase activity in hypothyroidism and hyperthyroidism in
      humans.
AB  - Alterations of serum cholesterol levels are well recognized findings in
      hypothyroidism and hyperthyroidism. It remains unclear, whether thyroid hormones
      may affect serum concentrations of cholesterol through changes in the activity of
      cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolic
      conversion of cholesterol to bile acids. We determined serum concentrations of
      the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one, which reflects
      cholesterol 7 alpha-hydroxylase activity in the liver, in 19 patients with
      hypothyroidism and in 10 patients with hyperthyroidism before and after
      treatment, respectively. In patients with hypothyroidism, serum concentrations of
      cholesterol and LDL-cholesterol decreased by 33% (p < 0.0005) and 39% (p <
      0.0005), respectively, after replacement therapy with thyroid hormones. In
      contrast, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one (21.7 +/-
      15.8 ng/ml vs 24.5 +/- 18.1 ng/ml before treatment, n.s.) as well as serum HDL
      cholesterol were unchanged during substitution therapy. In patients with
      hyperthyroidism, serum concentrations of cholesterol and LDL-cholesterol
      increased by 27% (p < 0.01) and 39% (p < 0.01) after antithyroid treatment,
      respectively. Again, serum concentrations of 7 alpha-hydroxy-4-cholesten-3-one
      did not change significantly during treatment (15.8 +/- 12.6 ng/ml vs 14.7 +/-
      8.1 ng/ml before treatment, n.s.). These findings indicate that in humans,
      thyroid hormones influence serum lipid concentrations by other mechanisms than by
      affecting the activity of cholesterol 7 alpha-hydroxylase.

PMID- 9178028
TI  - Repeated administration of growth hormone-releasing hormone with or without
      previous administration of pyridostigmine in insulin-dependent diabetes mellitus.
AB  - In insulin dependent diabetes mellitus (IDDM) either elevated growth hormone (GH)
      levels or abnormal responses to specific as well as unspecific stimuli have been
      reported. As hyperglycemia is known to blunt GH response to various stimuli, a
      normal GH response to GHRH in presence of hyperglycemia should also be considered
      inappropriate. To investigate the mechanism underlying this inappropriate GH
      response, in 9 patients with IDDM, selected for normal GH response to GHRH, we
      studied the GH response to two consecutive GHRH boluses (1 microgram/kg), the
      second of which preceded 30 min before by pyridostigmine (120 mg p.o.). Seven age
      matched normal volunteers were evaluated as control group. Basal plasma glucose
      and serum GH levels were significantly higher in patients with IDDM than in
      normal subjects (184.4 +/- 9.6 vs 86.2 +/- 4.4 mg/dl, p < 0.01 and 2.4 +/- 1.0 vs
      1.0 +/- 0.4 microgram/l, p < 0.01 respectively). Both in normal subjects and in
      patients with IDDM the GH response to the second consecutive GHRH administration
      was lower than that of the first GHRH bolus (delta AUC: 82.5 +/- 28.3 vs 401.1 +/
      131.2 micrograms/l/h, p < 0.05 and 77.2 +/- 30.4 vs 336.8 +/- 60.0 p < 0.02,
      respectively). Pyridostigmine was able to restore the blunted GH responsiveness
      to the second GHRH administration in both groups, but this response was found
      higher in normal than in diabetic subjects (delta AUC: 1250.8 +/- 136.2 vs 527.5
      +/- 147.6, p < 0.01). Since the GH-releasing effect of PD is likely to be
      mediated by the inhibition of hypothalamic somatostatin release, our results
      suggest that there is also an impaired somatostatin tone in hyperglycemic type 1
      diabetic patients with normal GH response to GHRH.

PMID- 9178029
TI  - Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental
      circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on
      the plasma levels of IR-GHRH in normal adults.
AB  - The relation of the physiological releases of growth hormone-releasing hormone
      (GHRH) and growth hormone (GH) into the circulation in various conditions was
      investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The
      mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was
      10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in
      the level. The concentrations of IR-GHRH in plasma from the umbilical artery and
      umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively,
      and a marked arterio-venous gradient was observed in all 12 individuals examined.
      The plasma level of IR-GHRH in the maternal vein was significantly lower than
      that in the cord blood, but was similar to that in non-pregnant women. In normal
      adults, although there was no apparent fluctuation in the level of plasma IR-GHRH
      or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was
      detected followed by, or synchronized with the surge of plasma GH after oral
      administration of L-dopa. In contrast, on L-arginine infusion, no proportional
      elevation of plasma IR-GHRH with increase in plasma GH was observed. During and
      after intravenous infusion of somatostatin, the circulating IR-GHRH level did not
      increase, but on stopping the infusion there was an immediate and marked rebound
      surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma
      originates from the fetus and may have a primary role in enhancing secretion of
      GH which promotes growth in early human life, and 2) the participations of GHRH
      in the mechanisms of GH secretion seen after administrations of L-dopa, L
      arginine and somatostatin are different.

PMID- 9178030
TI  - Catecholamines stimulate steroid secretion of dispersed fowl adrenocortical
      cells, acting through the beta-receptor subtype.

PMID- 9178031
TI  - Insulin resistance syndrome and Lewis phenotype in healthy men and women.

PMID- 9178032
TI  - Thyroid response to exercise at low altitude (Jordan valley) is confined to
      changes in triiodothyronine (T3)

PMID- 9178033
TI  - Behavioral symptoms in adult rats after postnatal L-nitro-arginine.
AB  - We addressed experimentally the suggestion by Gally et al. [Gally J. A., Read
      Montague P., Reeke G. N. Jr and Edelman G. M. (1990) Proc. Natl Acad. Sci. U.S.A.
      87, 3547-3551] that nitric oxide may play a role in the use-dependent
      modification of synaptic efficacy in the developing nervous system. In a
      preliminary control experiment, we treated rat pups from postnatal day 8 to
      postnatal day 22 with a nitric oxide synthase blocker (L-nitro-arginine) and
      compared their growth curves and brain weights to those of saline injected
      control pubs. No significant differences were found after the 14 days of nitric
      oxide synthase inhibition. In the subsequent experiment, we inhibited nitric
      oxide synthesis in rat pups from postnatal day 8 to day 29 and assessed their
      place learning ability and open field behavior as adults. We found an increased
      speed of habituation of locomotion in an open field in 5-month-old rats that had
      been treated postnatally with a nitric oxide synthase blocker. There was no
      difference between treated and non-treated rats with respect to place learning in
      a water maze. We conclude that perturbation of nitric oxide production during
      early postnatal development does not preclude normal learning and memory function
      in the adult.

PMID- 9178034
TI  - Weaver mutant mouse cerebellar granule cells respond normally to chronic
      depolarization.
AB  - We studied the effects of chronic K(+)-induced membrane depolarization and
      treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule cells (CGCs)
      from weaver mutant mice and non-weaver litter-mates. The weaver mutation is a Gly
      to-Ser substitution in a conserved region of the Girk2 G protein-coupled inward
      rectifying potassium channel [Patil N., Cox D. R., Bhat D., Faham M., Myers R. M.
      and Peterson A. S. (1995) Nature Genet. 11, 126-129] which induces early death of
      CGCs. The biochemical differentiation of CGCs was estimated as the rate of 2
      deoxy-D-glucose accumulation and the expression of neural cell adhesion molecule
      (NCAM). High (25 mM) K+ ion concentration or treatment with NMDA greatly promoted
      the biochemical differentiation of both weaver mutant and non-weaver litter-mate
      mouse CGCs. In contrast to the marked effect on biochemical differentiation in
      both weaver and non-weaver mice CGSs, chronic high K+ treatment only had limited
      effect on survival. The survival of weaver mutant mouse CGCs in medium containing
      5 mM K+ ions was very low, only 20% of the plated cells surviving at 7 days after
      plating, as opposed to the 50% for non-weaver CGCs. Chronic high K+ treatment
      improved the relative survival of weaver mutant mouse CGCs 1.6 2.2-fold and that
      of non-weaver CGCs 1.2-1.4-fold; the same number of CGCs (about 20% of the plated
      cells) were rescued by high K+ in both types of culture. The findings indicate
      that, in culture weaver mutant mouse, CGCs have a normal response to membrane
      depolarization and that the normal function of the Girk2 potassium channel is not
      critical for the survival of differentiated CGCs.

PMID- 9178035
TI  - Enhanced GABA release in cell-damaging conditions in the adult and developing
      mouse hippocampus.
AB  - The release of [3H]GABA from hippocampal slices from adult (3-month-old) and
      developing (7-day-old) mice was studied in cell-damaging conditions in vitro
      using a superfusion system. Cell damage was induced by modified superfusion
      media, including hypoxia, hypoglycemia, ischemia, the presence of Free radicals
      and oxidative stress. The basal release of GABA from the immature and mature
      hippocampus was generally markedly increased in all cell-damaging conditions. In
      7-day-old mice the release was enhanced most in the presence of free radicals.
      1.0 mM NaCN and ischemia, whereas in the adults 1.0 mM NaCN provoked the largest
      release of GABA, followed by ischemia and free radical-containing media.
      Potassium stimulation (50 mM K+) was still able to potentiate the release in all
      cell-damaging conditions in both age groups. It was shown by superfusing the
      slices in Ca- and Na-free media that ischemia-induced GABA release was Ca
      independent, occurring by a reversed operation of Na-dependent cell membrane
      carriers in both adult and developing hippocampus. Glutamate and its receptor
      agonists, N-methyl-D-aspartate (NMDA), kainate and 2-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA), potentiated GABA release only in the immature
      hippocampus by a receptor-mediated mechanism. The enhancement by kainate and AMPA
      receptors also operated under ischemic conditions. The massive amount of GABA
      released simultaneously with excitatory amino acids in the mature and immature
      hippocampus may be an important protective mechanism against excitotoxicity,
      counteracting harmful effects that lead to neuronal death. The GABA release
      induced by activation of presynaptic glutamate receptors may contribute
      particularly to the maintenance of homeostasis in the hippocampus upon impending
      hyperexcitation.

PMID- 9178036
TI  - Induction of c-fos mRNA by lead in PC 12 cells.
AB  - Addition of lead acetate to PC 12 pheochromocytoma cells elicits induction of c
      fos, an immediate early response gene. Induction of c-fos was concentration- and
      time-dependent: the lowest concentration of lead acetate tested that induced c
      fos was 10 microM; induction was observed after a 30 min incubation and remained
      high after 90 min. Treatment with lead acetate and cycloheximide superinduced c
      fos mRNA. Actinomycin D, an inhibitor of mRNA transcription, decreased the level
      of c-fos mRNA induced by lead acetate by almost 80%. Cadmium chloride and zinc
      chloride did not induce c-fos mRNA. Since the c-fos gene encodes a transcription
      factor, Pb2+ has the potential to deregulate the expression of other genes.

PMID- 9178037
TI  - A comparative study of the distribution of alpha- and gamma-enolase subunits in
      cultured rat neural cells and fibroblasts.
AB  - We report the presence and distribution of alpha (ubiquitous) and gamma (neuron
      specific) subunits of the dimeric glycolytic enzyme enolase (2-phospho-D
      glycerate hydrolase) in cultured neural cells. The gamma gamma enolase is found
      in vivo at high levels only in neurons and neuroendocrine cells. Neuronal cells
      in culture also contain relatively high levels of alpha gamma and gamma gamma
      enolase. Here we show, by enzymatic and immunological techniques, that the gamma
      subunit also is expressed in cultured rat astrocytes and meningeal fibroblasts
      and, as we previously reported, in oligodendrocytes. Both neuron-specific
      isoforms alpha gamma and gamma gamma are expressed in all these cells, but the
      alpha alpha isoform accounts for the major part of total enolase activity. The
      sum of alpha gamma and gamma gamma enolase activities increases with time in
      culture. i.e. maturation processes, reaching the highest level in
      oligodendrocytes (40% of total enolase activity) and 15 and 10% of total
      enzymatic activity in astrocytes and fibroblasts, respectively. The gamma enolase
      transcripts were found not only in cultured neuronal cells but also in cultured
      oligodendrocytes astrocytes, and meningeal fibroblasts. Our data indicate that
      neuron-specific enolase should be used with caution as a specific marker for
      neuronal cell differentiation.

PMID- 9178038
TI  - Localisation and expression of metallothionein immunoreactivity in the developing
      sheep brain.
AB  - Metallothioneins are small cysteine-rich proteins that bind heavy metals. In
      higher mammals there are complex families of metallothionein isoforms, which are
      well characterised at the DNA level but less so in terms of their cellular
      expression and function. In particular, little is known about the localisation of
      metallothionein in the developing mammalian brain. In this study using sheep
      fetuses, we have shown that metallothionein 1 and 2 isoform expression undergoes
      shifts in regional and cellular localisation during development of the brain.
      Metallothionein 1 and 2 expression is first detected by embryonic days E72 E73
      (gestation is 150 days) at the mRNA level and the metallothionein protein is
      observed in cells of the proliferating ventricular zones. Subsequent expression
      is detected in radial glial cells, oligodendrocytes and astrocytes in several
      regions of the brain, most notably the cerebral cortex. In the adult brain,
      metallothionein is expressed in astrocytes but not in oligodendrocytes. Double
      labelling immunohistochemistry using the glial fibrillary acidic protein (GFAP)
      an astrocyte marker, and metallothionein revealed that although there is an
      overlap in the profiles of the two proteins, there is no simple correlation in
      their expression. These observations are consistent with metallothionein, under
      physiological conditions, being regulated mainly by intracellular factors.

PMID- 9178039
TI  - Properties of developing lateral geniculate neurones in the mouse.
AB  - This study describes the properties of neurones recorded in vitro from the dorsal
      lateral geniculate nucleus (dLGN) of the mouse between developmental stages E16
      and P36 and represents the first systematic study of the development of rodent
      thalamic neurones. The results demonstrate that thalamo-cortical neurones in the
      mouse dLGN undergo a series of important changes as they mature. Prenatally
      recorded cells had low resting potentials and could not generate action
      potentials but as they mature, mouse dLGN neurones become more polarised and show
      an increase in membrane time constant and spike threshold, while action
      potentials increase in amplitude and decrease in width. The low-threshold spike
      (LTS) complex appears at the time of birth, but does not show properties typical
      of adult cells until at least the third postnatal week. Immature action
      potentials are primarily sodium-dependent but gain a significant calcium
      component in the second postnatal week, which is associated with a supra
      threshold oscillation of the membrane potential. The electrical activity during
      this critical period is strongly influenced by the interaction of powerful inward
      and outward rectification with calcium conductances which determines the
      appearance of voltage responses to intracellular current injection. The membrane
      potential in recordings from neurones during the first postnatal week was
      dominated by intense TTX-sensitive depolarising synaptic-like events which
      attained amplitudes of 60 mV in several neurones at stages P5-P8. These changes
      are discussed in relationship to the formation of appropriate connections in the
      developing visual system.

PMID- 9178040
TI  - Development of vulnerability to hypoxic damage in in vitro hippocampal neurons.
AB  - We investigated the relationship between sensitivity to hypoxia and culture age
      in in vitro hippocampal neurons. Hypoxia was induced by 24 hr incubation in an
      oxygen-free environment. Up to 6 days in vitro (DIV) mortality was very low or
      negligible, with few exceptions. Starting at 7 DIV, significant mortality began
      to be observed; in the age range 7 10 DIV, mortality of 50% or more was observed
      in five out of 11 experiments (45%) and average mortality was 51 +/- 15% (mean +/
      standard deviation, N = 11). In older (12 18 DIV) cultures, mortality of 50% or
      more was the rule (13 out of 13 experiments) and average mortality was 83 +/- 16%
      (mean +/- standard deviation, N = 13). The data could be fitted by a sigmoid line
      (r = 0.87, P < 10(-6) in which 50% mortality corresponds to 8.6 DIV. The N-methyl
      D-aspartate antagonist amino-phosphono-valerate and the nitric oxide synthase
      inhibitor nitroarginine both provided protection. Degree of protection was
      comparable for the two compounds, but was not observed in cultures younger than
      approximately 7 DIV. By contrast exogenous creatine was not protective, at
      variance with findings from other models. The data represent the first
      description of how sensitivity to hypoxic damage varies during the lifetime of an
      in vitro neuronal hippocampal culture. Moreover, they suggest the hypothesis that
      some maturational changes occurring at 79 days in vitro may make previously
      resistant in vitro neurons significantly sensitive to hypoxic damage, and that at
      least some of these changes may reflect the development of N-methyl-D-aspartate
      mediated glutamatergic transmission.

PMID- 9178041
TI  - Implantation of cultured human leptomeningeal cells into rat brain.
AB  - Since previous studies have shown that cells cultured from human leptomeninges
      can express neuronal and glial antigens under appropriate culture conditions
      [DeGiorgio L. A. et al. (1994) J. Neurol. Sci. 124, 141 148; Bernstein J. J. et
      al. (1996) Int. J. Derl Neurosci. 14(5), 681 687], we have studied the
      developmental characteristics of these cells further by grafting them into young
      adult rat brains. Cells were labeled in culture with Fast Blue and were
      identified unequivocally by hybridization with nick-translated human DNA.
      Intensely Fast Blue positive human leptomeningeal cells were concentrated in the
      implant pocket and adjacent rat leptomeninges al one and two weeks postimplant.
      Human and rat leptomeningeal cells were similar morphologically and were equally
      immunopositive for vimentin and fibronectin. Implanted human cells did not
      express the neuronal and glial proteins they had in vitro. Cells which hybridized
      with human DNA corresponded to the intensely Fast Blue positive cells. Small
      groups of human DNA hybridizing cells were also observed in the choroid plexus.
      Less intensely Fast Blue positive neurons and glia were found in the brain but
      these hybridized with rat DNA. A minority of human leptomeningeal cells implanted
      into rat brain are subsequently found in host leptomeninges where they
      demonstrate properties characteristic of leptomeningeal fibroblasts. Small
      numbers of implanted cells can survive for two weeks.

PMID- 9178042
TI  - Developmentally regulated release of intraretinal neurotrophic factors in vitro.
AB  - The effects of conditioned media either from aggregates or from explants of
      embryonic chick retinae and of recombinant neurotrophins were tested upon the
      survival in vitro of ganglion cells in dissociated cell cultures from the retina
      of newborn rats. Ganglion cells were identified by the detection of retrogradely
      transported horseradish peroxidase injected bilaterally into the superior
      colliculus. Conditioned media increased significantly the survival of ganglion
      cells after 2 days in culture, at a wide range of plating densities, and had no
      effect upon adhesion of rat retinal cells. Media conditioned by cell ensembles
      from chick retinae from embryonic day 8 (E8) to E16 had neurotrophic effects.
      Release of neurotrophic activity peaked at E10 E12, irrespective of the numbers
      of cells or total concentration of protein in the conditioned media. The active
      molecules were non-dialyzable and were released either in the presence or in the
      absence of fetal calf serum. The neurotrophic activity was abolished by
      trypsinization, and recovered by salting-out with 25 75% ammonium sulfate. NT-4,
      BDNF and, to a lesser extent, NT-3, increased the survival of ganglion cells in
      our assay, while NGF had no effect. The data show that chick retinal cells
      release soluble trophic proteins according to a developmentally regulated
      pattern. These neurotrophic factors may be involved in local competitive
      interactions that help control naturally occurring neuron death among ganglion
      cells of the vertebrate retina.

PMID- 9178043
TI  - Postnatal changes of brain monoamine levels in prenatally malnourished and
      control rats.
AB  - The effects of age and prenatal protein malnutrition (6% casein diet) on the
      concentration of monoamine neurotransmitters and their metabolites and precursors
      in the hippocampal formation, striatum, brain stem and cerebral cortex were
      investigated in 1-, 15-, 30-, 45-, 90- and 220-day-old rats. Concentrations of
      all neurotransmitters, i.e. dopamine, norepinephrine and serotonin changed
      significantly during the development. However, two main patterns were recognized.
      Serotonin in all areas, and dopamine in the striatum, increased from birth to day
      45, and declined significantly in 90-day-old rats. In contrast, norepinephrine in
      all areas, and dopamine in areas other than the striatum, showed the lowest
      levels in 30-day-old rats, with levels increasing gradually after this age.
      Concentrations of metabolites paralleled changes in corresponding
      neurotransmitter levels. Prenatal protein malnutrition did not significantly
      affect any neurotransmitter concentrations with the exception of increased
      tryptophan levels (181%) in the hippocampal formation of newborn rats and
      decreased tyrosine levels (59%) in the striatum of day 30 rats. The results
      indicate that the monoamine transmitter content varied dynamically throughout
      postnatal life; however, they seem to counteract the insult from prenatal protein
      malnutrition after postnatal nutritional rehabilitation.

PMID- 9178044
TI  - Tribute to Elaine Murphy.

PMID- 9178045
TI  - Mental health care for the elderly.

PMID- 9178046
TI  - Psychiatry of the elderly: a consensus statement.
AB  - This consensus statement, published by The Division of Mental Health and
      Prevention of Substance Abuse of the World Health Organisation, was co-sponsored
      by WHO and the Geriatric Section of the World Psychiatric Association, under the
      Section presidency of Professor J. Wertheimer. The final statement was prepared
      by an inter-disciplinary group representing the principal international
      association, at a meeting in Lausanne, 5-7 February 1996, chaired by Professor H.
      Hafner. Professor Cornelius Katona and Dr. Nori Graham were co-rapporteurs. A
      full list of participants is available from Professor Wertheimer.

PMID- 9178047
TI  - The Center for Epidemiological Studies-Depression (CES-D) Scale: assessment of
      depression in the medically ill elderly.
AB  - This study examines the use of the Center for Epidemiological Studies-Depression
      Scale (CES-D) in a sample of elderly, medically ill inpatients. Seventy-six
      individuals completed the CES-D and a psychiatric interview, from which DSM-III-R
      diagnoses of depression were obtained. Analyses of sensitivity and specificity
      indicated that use of an alternative scoring method which more closely
      approximates current diagnostic criteria for depression may improve the
      predictive power of the test. Employment of stringent cut-scores was not
      supported, as sensitivity was compromised. Item analyses demonstrated that seven
      of the CES-D items failed to discriminate major, minor and nondepressed patients,
      and that several of these items tapped somatic symptoms. These findings suggest
      that the validity of the CES-D may be compromised when used with elderly medical
      patients. and modifications for its use are recommended.

PMID- 9178048
TI  - Sexual relationships in married dementia sufferers.
AB  - OBJECTIVE: To determine the proportion of couples, one of whom suffers from
      dementia, continuing with a sexual relationship, their level of satisfaction with
      their sexual relationship and the associations of remaining sexually active.
      DESIGN: A survey of married couples enrolled in a prospective dementia study.
      SETTING: Psychiatric services and a memory clinic. SAMPLE: The partners of 47
      married patients with mild to moderate dementia. MEASURES: The assessment
      included the GMS/HAS/SDS package, the Marital Intimacy Scale (with some
      additional questions regarding sexual relations), the CAMCOG, the Carers Stress
      Scale, the Cornell Depression Scale and the Burns Symptom Checklist. Dementia was
      diagnosed according to DSM-III-R, McKhann, McKeith, Hachinski and HAS AGECAT
      criteria. RESULTS: Forty partners completed the study. Nine (22.5%) continued to
      have a sexual relationship, all of whom were satisfied with the situation. Twelve
      (38.7%) of the carers who were not sexually active were dissatisfied with the
      absence of a sexual relationship. There was a trend for male carers to be more
      likely to be involved in a continuing sexual relationship. Dissatisfaction with
      the absence of a sexual relationship was significantly associated with a
      diagnosis of vascular dementia in the patient and showed a trend towards an
      association with younger patient age. CONCLUSIONS: Nearly a quarter of married
      dementia sufferers are involved in a continuing sexual relationship, emphasizing
      the importance of further research in this area.

PMID- 9178049
TI  - Health-related quality of life in older patients with schizophrenia and other
      psychoses: relationships among psychosocial and psychiatric factors.
AB  - OBJECTIVE: Few multivariate studies relating psychosocial factors to symptoms of
      psychosis among older patients exist. We assessed environmental stressors,
      satisfaction with emotional support, coping responses and psychiatric symptoms,
      and sought to relate these factors to quality of well-being among older patients
      with schizophrenia and other psychoses. METHOD: Subjects were 70 psychosis
      patients with a mean age of 58. Predictors included measures of stressors (number
      of negative life events), satisfaction with emotional support, coping responses,
      positive and negative symptoms, depressive symptoms, social adjustment and a
      general quality of well-being (QWB) score. RESULTS: A conceptual model was tested
      and modified using path analytic techniques. Preliminary analyses suggested that
      psychosocial environment (life events, coping and emotional support) was
      primarily a product of psychiatric symptoms. Therefore, psychiatric symptoms
      preceded psychosocial environment variables in the proposed model. Further
      results suggested that depression mediated all of the effects of psychotic
      symptoms on social maladjustment, but not all of their effects on well-being.
      CONCLUSIONS: In older patients with schizophrenia and other psychoses, health
      related quality of well-being is influenced by symptoms of psychoses,
      psychosocial factors and social maladjustment.

PMID- 9178050
TI  - Differentiating between demented and psychiatric patients with the Dutch version
      of the IQCODE.
AB  - This study presents psychometric data on the Dutch version of the Informant
      Questionnaire on Cognitive Decline in the Elderly (IQCODE-N). We focused on
      differentiating between inpatients with dementia or a mood/psychotic disorder. A
      cutoff point of 3.9 on the IQCODE-N correctly predicted group membership in 87.8%
      and 78.8% respectively. Internal consistency and principal component analysis
      suggest that the IQCODE-N measures a unidimensional construct. Correlations with
      a Dementia Screening Test (r = 0.62), nurses' observations on memory disorders (r
      = 0.71) and a global assessment of severity of dementia (r = 0.72) support the
      validity of the informant ratings. Patients' age and level of education did not
      confound informant ratings. Only a small fraction of the informants could not
      complete the IQCODE-N, which makes it an easily applicable rating scale for
      cognitive decline.

PMID- 9178051
TI  - Stress of caregivers of dementia patients in the Singapore Chinese family.
AB  - In a study of 50 family caregivers of elderly Chinese patients with dementia in
      Singapore, 28 (56%) scored five points or more on the 28-item General Health
      Questionnaire (GHQ). The GHQ scores correlated significantly with duration of
      care; presence of delusion, hallucination, depression, insomnia, incontinence and
      agitation; and the total score of the Behavioural Pathology in Alzheimer's
      Disease Rating Scale. On multiple regression analysis the only variables to
      achieve a significant relationship with the GHQ scores were duration of care,
      depression and the total behavioural score.

PMID- 9178052
TI  - Carers' knowledge of dementia and their expressed concerns.
AB  - OBJECTIVE: The authors wished to determine how much carers from different
      settings caring for patients with dementia knew about the disorder and elicit
      their main concerns about the disease. DESIGN: A survey questionnaire was
      administered to 136 carers. SETTING: Two old age psychiatric services and an
      Alzheimer's support group in urban areas of the UK. PARTICIPANTS: The carers came
      from one of three categories: (1) carers with no prior contact with elderly
      mental health services (preassessment group); (2) carers who had been in contact
      with mental health care professionals (postassessment group); (3) carers in
      contact with an Alzheimer's Disease Society support group. MEASURES: A
      questionnaire on the subject of dementia. Carers' worries about the disorder were
      also recorded. RESULTS: Carers in contact with an Alzheimer's support group were
      the most knowledgeable and carers in the preassessment group were the least
      knowledgeable on the subject of dementia. While carers in the postassessment
      group had a level of knowledge above that of the preassessment group, this
      difference failed to reach statistical significance. CONCLUSION: The study
      highlights the need for elderly mental health teams to evaluate their methods of
      dissemination of knowledge to carers, develop educational packages for carers and
      evaluate their effectiveness.

PMID- 9178053
TI  - Characteristics of elderly psychiatric patients retained in a state hospital
      during downsizing: a prospective study with replication.
AB  - OBJECTIVE: This study examined the clinical characteristics of elderly inpatients
      associated with retention in a large state hospital during a period of rapid
      reduction in the inpatient census. DESIGN: During the first year of the study all
      inpatients age 65 or greater were individually evaluated. Patients remaining in
      the hospital during the second year were reevaluated and followed for an
      additional year. Separate statistical analysis of the data allowed for
      replication of findings. SETTING: The study was conducted at Pilgrim Psychiatric
      Center, the largest state hospital in New York State. PARTICIPANTS: The entire
      inpatient population over the age of 65 were included in the study (N = 806). The
      average age of the sample was 76 years and 70% were assigned a lifetime research
      diagnosis of schizophrenia. The majority of patients were hospitalized for long
      periods (mean = 33.9 years) and had significant cognitive impairment. MAIN
      OUTCOME MEASURES: Cognitive functioning was assessed on the Clinical Dementia
      Rating Scale. Severity of psychiatric symptoms was evaluated on the PANSS.
      Occurrence of dangerous behavior and medical and psychiatric treatment were
      obtained from the patients' medical histories. MAIN RESULTS: The findings,
      replicated across assessments, were that patients retained had more severe
      symptoms of excitement, hostility and impulsive behavior than those discharged,
      while uncooperativeness, delusions, grandiosity and suspiciousness were also more
      severe in those retained than those discharged. CONCLUSIONS: Elderly patients who
      are very difficult to place are so characterized because of behavior disorders
      that are difficult to manage rather than psychotic symptoms, cognitive impairment
      or medical disorders.

PMID- 9178054
TI  - Coroner's verdicts in the elderly: a suicide or an open verdict?
AB  - OBJECTIVES: To identify variables, other than legal definitions, that may have
      influenced North Cheshire's Coroner in returning a verdict of 'suicide' or an
      'open verdict' on unexpected deaths of the elderly. DESIGN: Retrospective review
      of all coroner's verdicts in North Cheshire during a 5-year period 1989-1993.
      MATERIAL: Forty-seven 'suicide' and 'open verdict' deaths in North Cheshire
      between 1989 and 1993 as defined in ICD classification 'E' codes E950-E959 and
      E980-E989, respectively, that were returned on the deceased aged 65 and above who
      died within North Cheshire. FINDINGS: Logistic regression analysis suggests that
      the Coroner's decision may be influenced by: intimation of intent, psychiatric
      history and method of death. Sex of the deceased, history of attempted suicide,
      social setting and history of alcohol problems did not appear significantly
      associated with coroner's verdict.

PMID- 9178055
TI  - Prevalence and correlates of aggressive behaviours occurring in patients with
      Alzheimer's disease.
AB  - OBJECTIVE: To determine the prevalence and clinical correlates of verbal and
      physical aggression occurring in Alzheimer's disease sufferers. DESIGN: A
      retrospective note review was performed to classify the subjects according to
      whether they were verbally or physically aggressive (assaultive) or non
      aggressive. The characteristics of the three groups were compared. SUBJECTS: The
      subjects were 262 patients who were living in non-institutional settings and had
      been diagnosed as suffering from dementia of Alzheimer's type. RESULTS: Fifty-two
      per cent exhibited some aggressive behaviour. Ninety-one (35%) patients were
      reported to be verbally aggressive and a further 46 (18%) were assaultive to
      their carers. Male gender (relative risk 2.17, 95% confidence interval 1.11-4.17)
      and the presence of dyspraxia (relative risk 2.89, 95% confidence interval 1.43
      5.88) both increased the likelihood of assaultive behaviour. Verbal aggression
      was not associated with any of the clinical features measured. CONCLUSION:
      Aggressive behaviour is a common phenomenon in AD and approximately one in five
      sufferers is assaultive. Assaultive behaviour is associated with male gender and
      dyspraxia.

PMID- 9178056
TI  - Behaviour therapy for obsessive compulsive disorder in a 78-year-old woman.
AB  - OBJECTIVE: To describe a case of late onset obsessive compulsive disorder (OCD)
      and determine the impact of a behavioural intervention on OCD symptoms. DESIGN: A
      single case design was undertaken in which the severity of the patient's OCD
      symptoms was measured before and after treatment. SETTING: The intervention was
      undertaken in the patient's home. PATIENT: A 78-year-old woman with a history of
      depression who experienced sudden onset and rapid escalation of OCD following a
      domestic accident. INTERVENTION: A behavioural procedure involving continuous in
      vivo exposure and response prevention over an 8-hour period. MEASURES: The Y-BOCS
      self-rating scale (Yale Brown Obsessive Compulsive Scale) and clinical
      observation. RESULTS: Y-BOCS score improved from 35 prior to treatment to 12 post
      treatment (mean for OCD population = 25.1; SD = 6, Goodman et al., 1989).
      Improvement was maintained at 2 months follow-up (Y-BOCS = 11). Improvements in
      confusion and agitation were also observed. CONCLUSIONS: This case study supports
      the use of behavioural interventions for elderly patients suffering from OCD.
      Risk factors and treatment designs are discussed in view of the literature.

PMID- 9178057
TI  - Designs for studies evaluating tests.

PMID- 9178058
TI  - Consumer satisfaction and outpatient ECT.

PMID- 9178059
TI  - Current awareness in geriatric psychiatry.

PMID- 9178060
TI  - Perceptions of coercion in the admission of voluntary and involuntary psychiatric
      patients.

PMID- 9178061
TI  - The reformulated defence of insanity in the Australian Criminal Code Act 1995
      (Cth).

PMID- 9178062
TI  - Closing state mental hospitals in Massachusetts: policy, process, and impact.

PMID- 9178063
TI  - Somatic morbidity in patients examined in forensic psychiatry.

PMID- 9178064
TI  - Patient perceptions of coercion in mental hospital admission.

PMID- 9178065
TI  - Violence of psychotic patients: how much responsibility can be attributed?

PMID- 9178066
TI  - Forensic conditional release programs and outcomes in three states.

PMID- 9178067
TI  - The rights of psychiatric patients in the light of the principles announced by
      the United Nations: a recognition of the right to consent to treatment?

PMID- 9178068
TI  - Predictors of recidivistic violence in criminally insane and civilly committed
      psychiatric inpatients.

PMID- 9178069
TI  - B-cell activation and tolerance. Introduction.

PMID- 9178070
TI  - CD40: a pivotal receptor in the determination of life/death decisions in B
      lymphocytes.
AB  - CD40 is a 48 kDa glycoprotein predominantly expressed on B cells in both mouse
      and man, which interacts with a counterligand (CD40L), expressed on activated
      CD4+ T cells. CD40/CD40L interactions are now known to be essential for the
      initiation of antibody responses to T-dependent antigens. In this review we
      discuss the immunobiology of CD40, with a special emphasis on our own studies in
      the mouse. These have focused on signal transduction via CD40, the role of
      cytokines (both T cell-derived and B cell-derived) in CD40-mediated B cell
      activation, and the role of CD40 in protecting B cells from apoptotic cell death.
      The available data indicate clearly that this protein is a pivotal receptor on B
      cells, both for the delivery of activating signals and for promoting B cell
      survival.

PMID- 9178071
TI  - B-cell activation versus tolerance--the central role of immunoglobulin receptor
      engagement and T-cell help.
AB  - The critical variables responsible for the decision between activation and
      tolerance in the B-cell compartment were studied in the well-characterised hen
      egg lysozyme:antilysozyme transgenic model. Mature B-cells exposed to a low
      antigenic signal, which resulted in a receptor occupancy of between 5% and 25%,
      remained 'indifferent' (i.e. were neither activated nor tolerant), had a normal
      lifespan and recirculated through B-cell follicles. When receptor occupancy
      reached a critical threshold of approximately 50%, the B-cells became activated
      and moved to the outer T-cell zones where they died. This threshold appeared to
      be lower in the case of immature B-cells. On addition of T-cell help, however,
      the B-cells were rescued, proliferated and secreted antibody. Thus the outcome of
      the interaction between B-cells and antigen (self or foreign) is determined
      largely by the degree of antigen receptor engagement and availability of T-cell
      help.

PMID- 9178072
TI  - Apoptosis and the B cell response to antigen.
AB  - The primary B cell response to T cell dependent antigens comprises two pathways
      of differentiation; one resulting in formation of foci of antibody forming cells
      in the extrafollicular regions of secondary lymphoid organs and the other giving
      rise to germinal centers within the follicles. Foci of antibody forming cells are
      detectable for only a limited time, before involuting due to apoptosis of the
      plasma cells. Similarly in the germinal center, regulation of cell number,
      selection of high affinity variants generated by somatic hypermutation, and the
      resolution of the germinal center itself all involve the death of unwanted B
      cells. In this review we describe recent experiments which have allowed
      determination of the role of certain forms of apoptosis in the B cell response to
      antigen.

PMID- 9178073
TI  - The role of T cells in the regulation of B cell tolerance.
AB  - The study of conventional models of B cell tolerance has suggested that self
      tolerance is imposed on B cells at an early stage in their development due to a
      peculiar sensitivity of immature B cells to tolerance induction. While this
      concept accounts for some aspects of central B cell tolerance, it is inconsistent
      with recent reports of tolerance induction in mature splenic B cells from
      immunoglobulin transgenic mice. We present an alternative model, the hierarchical
      model (Aust. N. Z. J. Med. 25, 761-767, 1995), in which regulation of naive B
      cell reactivity is a function of antigen signal strength and availability of T
      cell help, but is independent of B cell maturation stage. In turn, the
      development of tolerance or memory in the T cell compartment is dependent on a
      combination of antigen-MHC recognition by T cells and antigen-nonspecific
      signalling by antigen-presenting cells. Using a transgenic model of T-B
      collaboration, we have shown that both immature and mature self-reactive B cells
      can be rescued and induced to secrete auto-antibody if the B cell determinant is
      linked to a carrier protein bearing a foreign T cell determinant.

PMID- 9178074
TI  - The importance of efficacy and partial agonism in evaluating models of B
      lymphocyte activation.
AB  - Immunologists have developed a range of in vitro techniques for probing the
      receptor mediated response of cells comprising the immune system. An important
      and ubiquitous method is the use of antibodies in either soluble or aggregated
      form to engage cell surface receptors and transmit a signal. Models of cell and
      molecular interactions, derived from the use of these antibodies, form the basis
      of our efforts to understand and explain the corresponding in vivo systems.
      However, interpreting in vitro experiments and distinguishing between alternative
      models is difficult. This complexity is illustrated here using B cell stimulation
      by surface immunoglobulin and CD40. The fluorescent cell labelling dye
      carboxyfluorescein, diacetate, succinimidyl ester (CFSE) is used to show that
      many anti-Ig and CD40 stimulatory agents, used to assess the role of B cells and
      lymphokines, are partial agonists. By modelling each step in B cell signalling,
      activation and division it is possible to show that small changes in signal
      contributed by a second receptor can generate numerous distinct dose response
      curves that are highly dependent on the "efficacy" of signal transmission by the
      primary ligand and the number of cell divisions taken in culture. Differences in
      dose response curves become particularly striking if the primary activating
      stimulus is a partial agonist. Although exemplified here with B cell stimulation
      the conclusions are applicable to other in vitro activation systems and suggest
      ways to improve both the design and interpretation of in vitro experiments.

PMID- 9178075
TI  - Obesity: the search goes on.

PMID- 9178076
TI  - Evaluation of a summer camp for adolescents with eating disorders.

PMID- 9178077
TI  - Association between a history of childhood sexual abuse and subsequent,
      adolescent psychoactive substance use disorder in a sample of HIV seropositive
      men.
AB  - PURPOSE: Examine whether an association exists between having a sexual abuse
      history and having a psychoactive substance use disorder (PSUD) history in a
      population of HIV seropositive men. METHODS: Survey study of 95 HIV seropositive
      men. Sociodemographic and sexual abuse histories obtained before administration
      of the Standardized Clinical Interview for DSM-III-R (SCID-NP-HIV)-used to
      identify PSUD. RESULTS: Nineteen (20%) subjects had sexual abuse histories.
      Sexual abuse occurred early (mean age: 8.1 years). Ten (53%) subjects reported
      oral (n = 4) and/or anal (n = 9) penetration by perpetrator. Comparing men with
      histories of sexual abuse to men without, the odds ratio (OR) for subsequent
      injection drug use was 5.4 (1.5, 19.6), and for subsequent early (before age 20)
      injection drug use was 21.6 (3.4, 224.5). Adjusted ORs were 2.4 (0.55, 10.6) and
      12.2 (1.7, 90.3), respectively. CONCLUSIONS: In this sample of HIV seropositive
      men, an association between having been sexually abused and subsequently
      initiating injection drug use during adolescence exists. Future studies that more
      rigorously evaluate the possible causal nature of this association are indicated.

PMID- 9178078
TI  - Weekly and seasonal variation in sexual behaviors among adolescent women with
      sexually transmitted diseases.
AB  - PURPOSE: The objective of this research is to describe aspects of the
      organization of adolescent sexual behavior in order to understand factors
      associated with risk for sexually transmitted diseases (STD). METHODS: Subjects
      were 82 females (ages 16-19 years; 77% African-American) participating in a
      larger STD study. Subjects completed diaries for each coital event, recording
      date of event, partner initial, condom use, and use of drugs or alcohol before
      intercourse. Partner change was defined as any event for which the sex partner
      initials differed from those listed for the most recent previous coital event.
      RESULTS: The 82 subjects recorded 1265 coital events; the average span of the
      records was 10 weeks. Intercourse was least likely on Sundays (154 of 1265;
      12.2%) and most common on Friday and Saturday (221 of 1265 for each day; 17.5%).
      The proportion of coital events associated with drugs or alcohol increased from
      Sunday to Saturday, although the proportion of coital events in which a condom
      was used did not vary significantly. Intercourse was most common in spring and
      summer, and least frequent in winter. CONCLUSIONS: These data indicate
      substantial temporal organization of adolescent sexual behaviors that may be
      related to risk of sexually transmitted diseases. Some STD-preventive
      interventions may be most effective when targeted to higher risk times.

PMID- 9178079
TI  - Effect of parental mental health status on adolescents' dietary behaviors.
AB  - PURPOSE: The purpose of this study was to explore whether adolescents of
      substance-abusing and depressed parents were more likely to have poor dietary
      behaviors than those in the health comparison families. METHODS: The sample
      consisted of 841 adolescents in families of substance-abusing parents, depressed
      parents, and parents without a diagnosable psychiatric disorder. All adolescents
      were given a food frequency questionnaire. RESULTS: Adolescents whose parents had
      substance abuse disorder had lower intakes of fruits and higher intakes of high
      fat foods, and also ate more frequently at fast-food restaurants and purchased
      more snacks. Adolescents whose parents were depressed had lower intakes of all
      food groups. Mother's mental health status impacted more on adolescents' dietary
      behaviors than did the father's mental health status. CONCLUSION: This research
      suggests that at-risk behaviors among youth of psychiatrically impaired parents
      may extend to food behaviors.

PMID- 9178080
TI  - Developmental and food profiles of infants born to adolescent and adult mothers.
AB  - OBJECTIVE: To compare developmental markers and dietary intake of infants born to
      lower socioeconomic adolescent and adult mothers. DESIGN: Sixty-one adolescent
      (age 14-18 years) and 60 adult (age 22-28 years) mothers met inclusion criteria
      of comparable socioeconomic status, age range, urban/rural residence, and
      distribution of infants by gender. SAMPLE/SETTING: Adolescent subjects were
      recruited in last trimester and adult mothers postpartum. Interviews were
      conducted when infants were about 6 and 12 months of age. Data included age of
      occurrence for eight markers, age at adding complementary foods, two 24-h dietary
      recalls, and two measurements of growth. RESULTS: Adolescent mothers reported a
      significantly earlier age at which the infant "holds a spoon by self" and "drinks
      alone from a trainer cup." Six other markers were not significantly different
      between groups. Adolescent mothers fed cereal significantly earlier than did
      adult mothers, but there were no significant differences for fruit, vegetables,
      and meat. At 12 months, infants of adolescents had intakes of vitamin D and iron
      which were < 100% of recommended allowances, as did infants of adult mothers for
      vitamin D, iron, and zinc. Dietary fat was significantly higher at 6 and 12
      months and vitamin C was lower at 12 months for infants of adolescents compared
      to the adult group. CONCLUSIONS: Compared to adult mothers, adolescent mothers
      reported earlier mean ages for developmental markers related to self-feeding, and
      introduced cereal earlier. In each group, selected nutrient intakes decreased
      from recommended amounts in the 6-12-month period. Fat intakes were significantly
      different between groups at 6 and 12 months.

PMID- 9178081
TI  - Lactational performance of adolescent mothers shows preliminary differences from
      that of adult women.
AB  - PURPOSE: The purposes of this study were to characterize milk production, milk
      composition, and the lactational behavior of adolescent mothers, and to compare
      their lactational performance with that of adult females. METHODS: Twenty-two
      lactating mothers, 11 adolescents and 11 adults, were studied at 6-week intervals
      between 6 and 24 weeks postpartum. Milk production was determined by the test
      weighing procedure. Milk nutrient composition was determined by standard chemical
      analyses. Frequency and duration of nursing and the use of supplemental formula
      and complementary foods were recorded. RESULTS: The amount of milk adolescents
      produced at 6, 12, 18, and 24 weeks postpartum ranged from 37-54% less (P < .05)
      than that of the adults and resulted in a 45% weaning rate at 18 weeks postpartum
      in the younger group. Milk nutrient concentrations were not significantly
      different between groups, with the exception of significantly higher sodium
      concentrations during early lactation in the adolescents' milk. Lactational
      behavior differed significantly between the adolescent and adult groups; however,
      with the exception of the lower frequency of daytime nursing and the tendency
      toward the early introduction of supplemental formula in the adolescent group,
      these behavioral differences were the result of the racial and ethnic differences
      between the two groups. The differences in lactational behavior did not
      contribute to the differences in milk production between the adolescents and
      adult mothers. CONCLUSIONS: This preliminary study suggests that milk production
      was reduced in adolescent mothers compared with adult females. Although
      behavioral strategies that increase the frequency of daytime nursing and reduce
      the frequency of supplemental feedings may enhance the milk production of
      adolescent mothers, other biological factors may account for their poorer
      lactational performance.

PMID- 9178082
TI  - Covariations of eating behaviors with other health-related behaviors among
      adolescents.
AB  - PURPOSE: The study objectives are: (1) to examine and compare patterns of
      covariation of a wide range of health behaviors among adolescent boys and girls;
      (2) to determine whether eating behaviors are part of a larger construct of
      health-related behaviors and to identify the behaviors with which they share
      underlying similarities; and (3) to determine whether youth engaging in other
      health-compromising behaviors are at risk for unhealthy eating. METHODS: Data
      were analyzed from the Minnesota Adolescent Health Survey, a classroom
      administered questionnaire, completed by 36,284 adolescents, in grades 7-12 from
      1986-87. RESULTS: Among boys, factor analysis revealed five factors: (1) risk
      taking behaviors, (2) school-related behaviors, (3) "quietly" disturbed behaviors
      (e.g., frequent dieting, self-induced vomiting, suicide attempts), (4) health
      promoting behaviors; and (5) exercise. Eating behaviors loaded on the construct
      of health-promoting behaviors with brushing teeth and seat belt use. Among girls,
      four similar factors emerged; however, exercise loaded on the construct of health
      promoting behaviors. Therefore, eating behaviors loaded with brushing teeth, seat
      belt use, and exercise among girls. Logistic regression analyses, controlling for
      sociodemographic and personal variables, revealed that boys and girls engaging in
      health-promoting behaviors were less likely to have unhealthy eating behaviors,
      while those engaging in quietly disturbed behaviors, risk-taking behaviors, and
      problematic school behaviors were more likely to have unhealthy eating behaviors.
      CONCLUSIONS: Eating behaviors appear to be part of a health-promoting behavioral
      construct and should not be viewed in isolation from other behaviors. Although
      eating behaviors do not appear to be part of the "problem behavior syndrome,"
      youth engaging in a wide range of health-compromising behaviors are at risk for
      unhealthy eating; emphasizing the need to target high-risk youth with health
      promotion programs.

PMID- 9178083
TI  - Black-white differences in body size perceptions and weight management practices
      among adolescent females.
AB  - OBJECTIVE: This study compares body size perceptions and weight management
      practices of black and white adolescent females. DESIGN: Subjects were selected
      through a statewide, three-stage sampling procedure designed to provide a sample
      statistically representative of high school students in South Carolina. SUBJECTS:
      Participants included black (n = 1824) and white (n = 2256) females, 14-18 years
      of age, enrolled in South Carolina public high schools. METHODS: Respondents were
      asked to assess their perceived body size as overweight, underweight, or about
      right. Self-reported weight management practices included dieting (reducing
      caloric intake), exercise, and other methods (including diet pills and vomiting).
      Chisquare analysis was used to assess the differences in body size perception and
      weight management behaviors. Polychotomous logistic regression was performed to
      examine association while controlling for socioeconomic status. RESULTS: Forty
      one percent of the white adolescents and 29% of the black adolescents perceive
      themselves as overweight (p < 0.005). In the week prior to the survey, 28% of the
      white adolescents and 13% of the black adolescents reported dieting 34% of the
      while versus 23% of the black adolescents reported exercising to lose weight; and
      45% of the white and 16% of the black students reported both dieting and
      exercising. Polychotomous logistic regression analysis showed that white
      adolescent girls were almost twice as likely to perceive themselves as overweight
      as black adolescent girls. The white students had 6.04 [95% confidence interval
      (CI), 1.77, 20.67] times the odds of using pills and vomiting and 3.76 (95% CI,
      2.99, 4.72) times the odds of engaging in dieting and exercising as methods of
      weight management compared to the black students. CONCLUSIONS: These findings
      suggest that white adolescents are more likely to perceive themselves as
      overweight than black adolescents and are more likely to engage in unhealthy
      weight management practices than black adolescents.

PMID- 9178084
TI  - Use of body mass index to monitor treatment of obese adolescents.
AB  - PURPOSE: Absolute weight loss may not always be the best measure of adherence and
      response to therapy in obese adolescents if weight gain owing to linear growth is
      not considered. We wished to compare short-term absolute weight and height
      changes with changes in body mass index (BMI) in a group of severely obese
      adolescents to determine the most meaningful measure of treatment response.
      METHODS: We analyzed weight, height, and BMI in 27 adolescents, 10-18 years of
      age, referred for management of severe obesity. Subjects attended clinic on at
      least three occasions within a 6-24-month period. Detailed profiles of usual
      daily food intakes, physical activities, and family and environmental
      structure/activities were obtained, and specific goals to achieve weight control
      were negotiated with adolescents and their families at each visit. Weight,
      height, and BMI at the initial visit and at the most recent visit were compared.
      RESULTS: While 48% of our population actually lost weight, 78% either had no
      change or a decrease in BMI during the observation period. Differences between
      initial and most recent heights and BMIs were statistically significant, but
      weight changes were not significant. CONCLUSIONS: In addition to weight, BMI
      should be routinely used and reported when monitoring the response to specific
      interventions in growing adolescents. Evaluation of weight alone may
      underestimate the adolescent's adherence to treatment goals.

PMID- 9178085
TI  - NMR study of the peptide present in the principal neutralizing determinant (PND)
      of HIV-1 envelope glycoprotein gp120.
AB  - The peptide sequence Gly-Pro-Gly-Arg-Ala-Phe (GPGRAF) is present in many
      principal neutralizing determinants (PND) of the human immunodeficiency virus
      type-1 (HIV-1). It has been shown that peptides from the PND sequence contain a
      significant beta turn in the conserved Gly-Pro-Gly-Arg sequence. In order to find
      out whether or not the smaller subunits also contain this turn, we have studied
      the NMR of a hexapeptide [GPGPRAF, peptide (I)], a heptapeptide Gly-Pro-Gly-Arg
      Ala-Phe-Cys [GPGRAFC, peptide (II)] and a dodecapeptide [GPGRAFGPGRAF, peptide
      (III)], retaining the side chain protecting groups. Although the majority of
      conformations for these peptides are disordered, there is a considerable
      propensity of structures with beta turn in the GPGR sequence. While peptide (I)
      and peptide (III) seem to have both type I and type II beta turn conformations,
      peptide (II) shows a propensity of only type II beta turn. The nascent structures
      obtained in these peptides may get stabilized as the receptor binding
      conformation in the presence of the receptors, thus playing a significant role in
      vaccine development against HIV.

PMID- 9178086
TI  - Simultaneous chromatographic analysis of eight fat-soluble vitamins in plasma.
AB  - A high-performance liquid chromatographic (HPLC) method for the simultaneous
      analysis of eight fat-soluble vitamins including A acid, retinol and retinal,
      vitamins D2 and D3 together with menadione (vitamin K3) is described. The eight
      vitamins extracted from plasma were analyzed by reversed-phase HPLC with UV
      detection at 245 nm. The mobile phase was composed of methanol and ethanol
      (85:15, v/v) with 0.1% triethylamine. The extraction efficiency of different
      solvents, namely, dichloromethane, benzene, methanol, ethanol, chloroform and
      hexane, with or without the addition of detergents was studied. There is no
      single solvent system that could extract all eight vitamins in one step. A
      recovery study of the vitamins was performed using rabbit plasma. An average
      recovery for individual vitamins was about 40% or more with the described
      extraction methods. The absorbance response was linear at the nanogram level. The
      present method may be broadly applied with alternative extraction methods for the
      eight vitamins from different sources.

PMID- 9178087
TI  - In vivo study of halothane hepatotoxicity in the rat using magnetic resonance
      imaging and 31P spectroscopy.
AB  - Using magnetic resonance imaging (MRI) and spectroscopy (MRS), in vivo halothane
      hepatotoxicity was assessed in male Wistar rats. With 1.5% halothane in 100 or
      20% O2, an edematous region, characterized by increased intensity on T2 weighted
      images and an increase in regional tissue water content (rho water), was seen
      proximal to the hepatic portal vein in the liver. Both spin-lattice relaxation
      (T1) and spin-spin relaxation (T2) increased in this region, relative to distal
      regions of the liver. Similarly, a high signal intensity on proton density
      weighted images was observed in this area. As halothane anaesthesia progressed, a
      decrease in the adenosine triphosphate-inorganic phosphate ratio (ATP/Pi) and an
      increase in the phosphomonoester-phosphodiester (PME/PDE) ratio was detected in
      the liver. In addition, intracellular pH decreased and intracellular free
      magnesium concentration [Mg2+] increased with time of exposure. Excessive
      vacuolation, ribosomal disappearance from rough endoplasmic reticulum,
      mitochondrial swelling and fragmentation of smooth endoplasmic reticulum were
      observed by transmission electron microscopy (TEM) in samples from the edematous
      region of the liver.

PMID- 9178088
TI  - Large-scale purification and long-term stability of human butyrylcholinesterase:
      a potential bioscavenger drug.
AB  - Butyrylcholinesterase from human plasma (HuBChE) is a potential drug candidate
      for detoxification of certain harmful chemicals that contain carboxylic or
      phosphoric acid ester bonds. Large quantities of purified HuBChE, displaying a
      high stability upon long-term storage, are required for the evaluation of its
      therapeutic capacity and its pharmaceutical properties. Several modifications of
      a previously reported procedure enabled us to purify the enzyme > 15,000-fold
      from pools of up to 100 1 of human plasma. The three-step procedure is based on
      precipitation of plasma proteins by ammonium sulfate (step I) and batch
      adsorption of HuBChE on procainamide-Sepharose 4B gel (step II). Ammonium sulfate
      was also employed in the third stage to fractionate the final product from
      procainamide-containing HuBChE solution. The overall yield (63%) of
      electrophoretically pure enzyme was significantly higher than that previously
      reported (34%) for the purification of HuBChE from 12.5 1 of plasma or from 5 kg
      of Cohn fraction IV-4. Purified HuBChE was stored at 5 degrees C in 10 mM
      phosphate buffer (pH 7.4) containing 1 mM EDTA and 0.02% NaN3. The specific
      activity, protein migration on gel electrophoresis, thermostability at 54 degrees
      C and the mean residence time in the circulation of mice remained essentially
      constant for at least 46 months. The modifications introduced can provide large
      quantities of purified enzyme that maintains its activity and bioavailability
      properties for several years.

PMID- 9178089
TI  - Determination of cell surface charge by photometric titration.
AB  - A colloid titration method has been frequently used to determine the number of
      charged residues at the cell surface. Here we present a new version of this
      technique, based on photometric measurements of a metachromatic shift in the
      maximum absorption of toluidine blue as it binds to the cell surface. The major
      improvements are: (1) simplified methodology and (2) increased precision of
      equivalence point determination. The data are analyzed using Gran's theory, which
      allows measurements to be taken at regular intervals instead of being
      concentrated around the equivalence titration point. We used this method to
      characterize the cell surface charge of three populations of rat mast cells: (1)
      peritoneal mast cells (PMC), (2) bone marrow-derived mast cells (BMMC) and (3) a
      rat cultured mast cell line (RCMC). Our results indicate that PMC have (4.23 +/-
      0.59) x 10(8), while BMMC (8.58 +/- 0.26) x 10(7) negatively charged residues per
      cell. The results for RCMC were similar to those for BMMC. Taking into account
      the size differences between PMC and BMMC, the average charge density of PMC was
      also significantly higher than that of BMMC. The differences in cell surface
      charge were analyzed in the light of different sensitivities of mast cells to
      polycationic secretagogues.

PMID- 9178090
TI  - Quantification of total RNA by ethidium bromide fluorescence may not accurately
      reflect the RNA mass.
AB  - The fluorescent signal from purified large and small ribosomal RNA subunits
      stained with ethidium bromide was quantified using agarose gels and image
      analysis. A significantly smaller fluorescent signal was observed for 23 S rRNA
      compared to 16 S rRNA when normalized to mass. Therefore, small changes in
      amounts of 23 S or 16 S rRNA within a sample can have a profound impact on
      observed bulk fluorescence. A comparison of 23 S/16 S rRNA fluorescence ratios
      for 4 marine bacteria grown in batch culture indicates that the lower
      fluorescence of 23 S rRNA is widespread. The 23 S/16 S rRNA fluorescence ratios
      also suggest that intracellular concentrations of ribosomal subunits do not
      always adhere to a stoichiometry of 2.0.

PMID- 9178091
TI  - Polyphenol oxidase activity staining in polyacrylamide electrophoresis gels.
AB  - An analytical method allowing the detection of polyphenol oxidase activity on
      polyacrylamide gel electrophoresis (PAGE) is described. The method is rapid,
      sensitive and specific and is based on a coupling reaction between 4-tert-butyl-o
      benzoquinone and the aromatic amine, 4-amino-N,N-diethylaniline sulphate.
      Catecholase activity of polyphenol oxidase appears as blue stained bands on a
      colourless background.

PMID- 9178092
TI  - Rapid, sensitive and specific detection of whole cells and spores using the light
      addressable potentiometric sensor.

PMID- 9178093
TI  - Advances and opportunities in delivery of therapeutic proteins and peptides.

PMID- 9178094
TI  - Influence of polyethylene glycol graftings on the in vitro degradation and
      calcification of bovine pericardium.
AB  - Calcification is a frequent cause of the clinical failure of bio-prosthetic heart
      valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). This
      article reports on various chemical techniques for grafting polyethylene glycol
      (PEG) on bovine pericardium, their biostability, and calcification. The process
      of calcification profile was studied by in vitro experiments via the incubation
      of pericardial samples in a metastable solution of calcium phosphate. The
      calcification profile of PEG-modified bovine pericardium through glutaraldehyde
      linkages was significantly reduced compared to other methods of grafting. The
      mechanical property of these PEG-modified tissues after enzyme (collagenase)
      digestion and calcification were also investigated. PEG grafting of BP via
      glutaraldehyde or hexamethylene diisocyanate had shown better mechanical
      stability compared to other grafting methods used. In conclusion, it seems that
      the surface modification of bovine pericardium through high molecular weight PEGs
      via glutaraldehyde linkages may provide new ways of controlling tissue
      biodegradation and calcification.

PMID- 9178095
TI  - Genetic and biochemical analysis of the transmembrane domain of Arabidopsis 3
      hydroxy-3-methylglutaryl coenzyme A reductase.
AB  - We have examined the amino terminal membrane anchoring domain of Arabidopsis
      thaliana 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmg1p), a key enzyme of
      the isoprenoid biosynthetic pathway. Using both in vitro and in vivo approaches,
      we have analyzed a series of recombinant derivatives to identify key structural
      elements which play a role in defining Hmg1p transmembrane topology. Based on our
      results, we have proposed a topological model for Hmg1p in which the enzyme spans
      the lipid bilayer twice. We have shown the two transmembrane segments, designated
      TMS1 and TMS2, to be structurally and functionally inequivalent in their ability
      to direct the targeting and orientation of reporter proteins. Furthermore, we
      provide evidence indicating both the extreme amino terminal end and carboxyl
      terminal domain of the protein reside in the cytosol. This model therefore
      provides a key basis for the future examination of the role of the transmembrane
      domain in the targeting and regulation of Hmg1p in plant cells.

PMID- 9178096
TI  - Differentiation of human trophoblast cells in vitro is inhibited by
      dimethylsulfoxide.
AB  - Dimethyl sulfoxide (DMSO) exerts a number of biological effects, the most
      frequently cited being induction of cell differentiation. The compound also
      increases invasiveness and metastatic potential. In contrast to the many reports
      of DMSO-induced cell differentiation, we report here that DMSO inhibits the
      morphological differentiation of human cytotrophoblast cells to
      syncytiotrophoblast, as revealed by immunofluorescence staining for desmosomal
      protein and nuclei. Cytotrophoblast cells treated with DMSO under differentiation
      inducing conditions remained mononucleated with intense desmosomals staining. The
      effect was dose dependent, with a maximal effect seen at 1.5% DMSO.
      Concentrations of < or = 0.5% had no effect and concentrations > 2% were
      cytotoxic. In addition to these morphological changes, DMSO inhibited secretion
      of human chorionic gonadotropin in a dose-dependent manner. At a concentration of
      1.5%, DMSO inhibited secretion by 70%. If cytotrophoblast cells were cultured in
      the presence of DMSO and then switched to DMSO-free medium, they proceeded to
      differentiate normally. While the precise mechanism of action remains unknown,
      judicious use of DMSO may be a useful tool for studying and manipulating the
      differentiation of human trophoblast cells in vitro. The findings also indicate
      that care should be used in interpreting results obtained using DMSO as a carrier
      in drug and inhibitor studies.

PMID- 9178097
TI  - Autoregulation of actin synthesis responds to monomeric actin levels.
AB  - Regulation of the assembly and expression of actin is of major importance in
      diverse cellular functions such as motility and adhesion and in defining cellular
      and tissue architecture. These biological processes are controlled by changing
      the balance between polymerized (F) and soluble (G) actin. Previous studies have
      indicated the existence of an autoregulatory pathway that links the state of
      assembly and expression of actin, resulting in the reduction of actin synthesis
      after actin filaments are depolymerized. We have employed the marine toxins
      swinholide A and latrunculin A, both disrupting the organization of the actin
      cytoskeleton, to determine whether this autoregulatory response is activated by a
      decrease in the level of polymerized actin or by an increase in monomeric actin
      concentrations in the cell. We showed that in cells treated with swinholide A the
      level of filamentous actin is decreased, and using a reversible cross-linking
      reagent, we found that actin dimers are formed. Latrunculin A also disassembled
      actin filaments, but produced monomeric actin, followed by a reduction in actin
      and vinculin expression, while swinholide A treatment elevated the synthesis of
      these proteins. In cells treated with both latrunculin A and swinholide A,
      dimeric actin was formed, and actin and vinculin synthesis were higher than in
      control cells. These results suggest that the substrate that confers an
      autoregulated reduction in actin expression is monomeric actin, and when its
      level is decreased by dimeric actin formation, actin synthesis is increased.

PMID- 9178098
TI  - Simultaneous activity of two different mechanisms of folate transport in ovarian
      carcinoma cell lines.
AB  - We investigated whether the folate receptor alpha-isoform (FR alpha), which is
      overexpressed on ovarian carcinoma cells, is functionally active in internalizing
      the physiological form et folate, 5-methyl tetrahydrofolate (THF). Six ovarian
      tumor cell lines, expressing different levels of FR alpha (COR > > OVCAR3 >
      IGROV1 > OVCAR4 > SKOV3 > OVCAR5), were maintained in folate-depleted medium and
      internalization of 10 nM evaluated as acid-resistant radioactivity at 0 degree
      and 37 degrees C. The amount of 5-methyl[1H]THF present in this fraction was not
      strictly related to the number of membrane receptors, since even cell lines with
      low FR alpha expression, e.g., OVCAR4, showed efficient internalization. Time
      course studies indicated that, whereas no uptake was detected at 0 degree C, at
      37 degrees C the internalized fraction showed a slow and constant increase, until
      4 h. At this time the internalized radioactivity represented < 50% of the total
      bound in COR, OVCAR3 and IGROV1 cells, whereas the other cell lines tested
      internalized fourfold more folate than their surface binding capacity. The
      incubation in the presence of a concentration (50 nM) of 5-methyl[3H]THF, which
      best ensures receptors saturation on cells with highest FR levels (COR and
      OVCAR3), had slight effect on surface binding of all the tested cell lines,
      including IGROV1 and SKOV3. In contrast, the increase of the uptake was more
      pronounced, particularly in SKOV3 cells. These results, together with the
      accumulation curves of folic acid (FA) and 5-methylTHF at 37 degrees C, suggested
      the presence of a molecule on ovarian carcinoma cells with high affinity for
      reduced folates, possibly a reduced folate carrier (RFC). Measurement of
      radioactivity present in the supernatant of IGROV1 and SKOV3 cells, subjected to
      hypotonic lysis and cell fractionation, further indicated that 5-methyl[3H]THF
      was translocated to the cytosol and, despite differences in membrane levels of FR
      alpha expression this internalized fraction was similar in both cell lines.
      Inhibition experiments to selectively block FR alpha or RFC activity showed a
      differential sensitivity of the two pathways depending on the cell line examined.
      Internalization was more consistently inhibited on IGROV1 than on SKOV3 cells by
      treatments that disrupt FR alpha activity, e.g., incubation with excess FA and
      phosphatidylinositol specific phospholipase C, whereas Probenecid, which
      preferentially inhibits the carrier-mediated pathway, showed a strong inhibitory
      effect on both cell lines. These findings suggest that the internalization of 5
      methylTHF in these tumor cells depends not only on the level of overexpressed FR
      alpha, but another transport route, with features characteristic for RFC, is
      functional and participates in folate uptake.

PMID- 9178099
TI  - Dexamethasone induces rapid actin assembly in human endometrial cells without
      affecting its synthesis.
AB  - Dexamethasone exerts a stimulatory effect of rapid-onset on the polymerization of
      actin. This has been documented in human endometrial adenocarcinoma Ishikawa
      cells, resulting in an acute, dose-dependent decrease in the G/total-actin ratio.
      In the present study we completely characterized this fast and apparently
      nongenomic effect of dexamethasone on actin assembly. We followed the
      morphological alterations of actin cytoskeleton and measured the time-dependent
      dynamics of actin polymerization both by ruling out any changes of total actin in
      the cells and by measuring its transcript. Rapid changes in actin polymerization
      were accurately measured using a highly sensitive and quantitative rhodamine
      phalloidin fluorimetric assay. Ishikawa cells, exposed to 0.1 microM
      dexamethasone for various time periods up to 24 h, showed a highly significant,
      rapid, and transient increase in the polymerization of actin starting within 15
      min of dexamethasone exposure and lasting 2 h. Treated cells showed a significant
      (1.79-fold) enhancement of the fluorescent signal compared to untreated cells at
      15 min. This value decreased continuously in a time-dependent manner, reaching
      control levels after 120 min and remained so for the next 24 h. Confocal laser
      scanning microscopy studies confirmed these findings. Intensive coloration of
      microfilaments over several scanning sections suggested an enhanced degree of
      actin polymerization in cells preincubated for 15 min with 0.1 microM
      dexamethasone. Moreover, actin filaments were more resistant to cytochalasin B.
      Additionally, quantitative immunoblot analysis showed that the content of total
      cellular actin remained the same during this period, suggesting that the
      biosynthesis of actin was unaffected. Northern blot analysis showed that the
      concentration of the actin transcript was also unaffected. Our data suggest that
      glucocorticoids induce a fast and self-limited polymerization of actin in human
      endometrial cells without affecting its synthesis. These findings strengthen the
      hypothesis that glucocorticoids exert rapid, nongenomic cellular effects and that
      the actin-based cytoskeleton is an integral part of this pathway, playing an
      essential role in receiving and mediating steroid signals for the modulation of
      cellular responses.

PMID- 9178100
TI  - Transforming growth factor-beta 1 regulation of bone sialoprotein gene
      transcription: identification of a TGF-beta activation element in the rat BSP
      gene promoter.
AB  - Transforming growth factor-beta (TGF-beta) increases steady-state mRNA levels of
      several extracellular matrix proteins in mineralized connective tissues. Bone
      sialoprotein (BSP) is a major constituent of the bone matrix, thought to initiate
      and regulate the formation of mineral crystals. To determine the molecular
      pathways of TGF-beta 1 regulation of bone proteins, we have analyzed the effects
      of the TGF-beta 1 on the expression of the BSP in the rat osteosarcoma cell line
      (ROS 17/2.8). TGF-beta 1 at 1 ng/ml, increased BSP mRNA levels in ROS 17/2.8
      cells approximately 8-fold: the stimulation was first evident at 3 hr, reached
      maximal levels at 12 hr and slowly declined thereafter. Since the stability of
      the BSP mRNA was not significantly affected by TGF-beta 1, and nuclear "run-on"
      transcription analyses revealed only a approximately 2-fold increase in the
      transcription of the BSP gene, most of the increase in BSP mRNA appeared to
      involve a nuclear post-transcriptional mechanism. Moreover, the effects of TGF
      beta 1 were indirect, since the increase in BSP mRNA was abrogated by
      cycloheximide (28 micrograms/ml). To identify the site of transcriptional
      regulation by TGF-beta 1, transient transfection analyses were performed using
      BSP gene promoter constructs linked to a luciferase reporter gene. Constructs
      that included nt -801 to -426 of the promoter sequence were found to enhance
      transcriptional activity approximately 1.8-fold in cells treated with TGF-beta 1.
      Within this sequence, approximately 500 nt upstream of the transcription start
      site, a putative TGF-beta activation element (TAE) was identified that contained
      the 5'-portion of the nuclear factor-1 (NF-1) canonical sequence (TTGGC)
      overlapping a consensus sequence for activator protein-2 (AP-2). The
      functionality of the TAE was shown by an increased binding of a nuclear protein
      from TGF-beta 1 stimulated cells in gel mobility shift assays and from the
      attenuation of TGF-beta 1-induced luciferase activity when cells were co
      transfected with a double-stranded TAE oligonucleotide. Competition gel mobility
      shift analyses revealed that the nuclear protein that binds to the TAE has
      similar properties to, but is distinct from, NF-1 nuclear protein. These studies
      have therefore identified a TGF-beta activation element (TAE) in the rat BSP gene
      promoter that mediates the stimulatory effects of TGF-beta 1 on BSP gene
      transcription.

PMID- 9178101
TI  - Reduced drug accumulation and multidrug resistance in human breast cancer cells
      without associated P-glycoprotein or MRP overexpression.
AB  - MCF-7 human breast cancer cells selected in Adriamycin in the presence of
      verapamil developed a multidrug resistant phenotype, which was characterized by
      as much as 100,000-fold resistance to mitoxantrone, 667-fold resistance to
      daunorubicin, and 600-fold resistance to doxorubicin. Immunoblot and PCR analyses
      demonstrated no increase in MDR-1 or MRP expression in resistant cells, relative
      to parental cells. This phenotype is similar to one previously described in
      mitoxantrone-selected cells. The cells, designated MCF-7 AdVp, displayed a slower
      growth rate without alteration in topoisomerase II alpha level or activity.
      Increased efflux and reduced accumulation of daunomycin and rhodamine were
      observed when compared to parental cells. Depletion of ATP resulted in complete
      abrogation of efflux of both daunomycin and rhodamine. No apparent alterations in
      subcellular daunorubicin distribution were observed by confocal microscopy. No
      differences were noted in intracellular pH. Molecular cloning studies using DNA
      differential display identified increased expression of the alpha subunit of the
      amiloride-sensitive sodium channel in resistant cells. Quantitative PCR studies
      demonstrated an eightfold overexpression of the alpha subunit of the Na+ channel
      in the resistant subline. This channel may be linked to the mechanism of drug
      resistance in the AdVp cells. The results presented here support the hypothesis
      that a novel energy-dependent protein is responsible for the efflux in the AdVp
      cells. Further identification awaits molecular cloning studies.

PMID- 9178102
TI  - Identification of Rad's effector-binding domain, intracellular localization, and
      analysis of expression in Pima Indians.
AB  - In order to characterize the endogenous gene product for rad (ras-related protein
      associated with diabetes), we prepared antibodies to synthetic peptides that
      correspond to amino acids (109-121, 178-195, 254-271) within the protein. These
      antibodies were used to analyze the expression, structure, and function of rad.
      Western analysis with these antibodies revealed that rad was a 46 kDa protein
      which was expressed during myotube formation. Further, immunolocalization studies
      showed that rad localized to thin filamentous regions in skeletal muscle.
      Interestingly, when muscle biopsies from diabetic and control Pima Indians were
      compared, no differences in rad protein or mRNA expression were observed.
      Similarly, no differences were observed in protein expression in diabetic and
      control Zucker diabetic fatty (ZDF) rats. Functional analysis of muscle rad
      revealed that its GTP-binding activity was inhibited by the addition of N
      ethylmaliemide, GTP, GTP gamma S, and GDP beta S but not ATP or dithiothreitol.
      Moreover, cytosol-dependent rad-GTPase activity was stimulated by the peptide
      corresponding to amino acids 109-121. Antibodies corresponding to this epitope
      inhibited cytosol-dependent rad-GTPase activity. Taken together, the results
      indicate that 1) rad is a 46 kDa GTP-binding protein localized to thin filaments
      in muscle and its expression increases during myoblast fusion, 2) expression of
      rad in Pima Indians and ZDF rats does not correlate with diabetes, and 3) the
      amino acids (109-121) may be involved in regulating rad-GTPase activity, perhaps
      by interacting with a cytosolic factor(s) regulating nucleotide exchange and/or
      hydrolysis.

PMID- 9178103
TI  - Alteration of the kinetics of type I procollagen synthesis in human osteosarcoma
      cells by 1,25-dihydroxyvitamin D3.
AB  - The kinetics of type I procollagen synthesis in a human osteosarcoma cell line,
      MG 63, were investigated after treatment with 1,25-dihydroxyvitamin D3 (1,25
      (OH)2 D3), a hormonal inducer of phenotypic differentiation. Pulse label and
      chase experiments demonstrated greatly enhanced production and more rapid
      reduction of intracellular procollagen molecules in the 1,25-(OH)2 D3-treated
      cells as compared to the nontreated case. After a chase for 1 h, labeled
      procollagen was reduced by nine-tenths in 1,25-(OH)2 D3-treated cells, while half
      of the radioactivity still remained in nontreated cells. The expression rate of
      type I collagen, which was examined by pulse label experiment, was elevated in
      association with an increase in the mRNA coding for the type I collagen alpha 1
      chain by 1,25-(OH)2 D3 treatment. However, the amount of intracellular
      procollagen present after 4 h continuous labeling was almost the same,
      independent of the 1,25-(OH)2 D3 treatment. Thus, we conclude that strage of the
      molecule was not affected. The results therefore suggest an increase in both the
      synthesis and secretion of type I collagen. The 1,25-(OH)2 D3 treatment was also
      found to induce the alpha subunit of prolyl 4-hydroxylase and to be associated
      with an elevated level of hydroxyproline in the procollagen. Moreover, gelatinase
      B-resistant procollagen molecules, indicative of intracellular procollagen
      molecules in the stable triple helical form, were detected only in the 1,25-(OH)2
      D3-treated cells. These data suggest more efficient proline hydroxylation is
      involved in rapid secretion of procollagen after hormone administration. The
      present evidence points to posttranslational control of procollagen synthesis.

PMID- 9178104
TI  - Partial isolation from intact cells of a cell surface-exposed
      lysophosphatidylinositol-phospholipase C.
AB  - A novel cell surface phosphoinositide-cleaving phospholipase C (ecto-PLC)
      activity was isolated from cultured cells by exploiting its presumed external
      exposure. Biotinylation of intact cells followed by solubilization of the
      biotinylated proteins from a membrane fraction and recovery onto immobilized
      avidin beads, allowed assay of this cell surface enzyme activity apart from the
      background of the substantial family of intracellular PLCs. Several cell lines of
      differing ecto-PLC expression were examined as well as cells stably transfected
      to overexpress the glycosylphosphatidylinositol (GP) anchored protein human
      placental alkaline phosphatase (PLAP) as a cell surface enzyme marker. The
      resulting bead preparations from ecto-PLC positive cells possessed calcium
      dependent PLC activity with preference for lysophosphatidylinositol (lysaPI)
      rather than phosphatidylinositol (PI). The function of ecto-PLC of intact cells
      evidently is not to release GPI-anchored proteins at the cell surface, as no
      detectable Ca(2+)-dependent release of overexpressed PLAP from ecto-PLC-positive
      cells was observed. To investigate the cell surface linkage of the ecto-PLC
      itself, intact cells were treated with bacterial PI-PLC to cleave simple GPI
      anchors, but no decrease in ecto-PLC activity was observed. High ionic strength
      washes of biotinylated membranes prior to the generation of bead preparations did
      not substantially reduce the lysoPI-PLC activity. The results verify that the
      ecto-PLC is truly cell surface-exposed, and unlike other members of the PLC
      family that are thought to be peripheral membrane proteins, this novel lysoPI-PLC
      is most likely a true membrane protein.

PMID- 9178105
TI  - Parathyroid hormone uses both adenylate cyclase and protein kinase C to regulate
      acid production in osteoclasts.
AB  - Osteoclasts, isolated from the endosteum of 2.5- to 3-week-old chickens, were
      treated with acridine orange, a hydrogen ion concentration-sensitive fluorescent
      dye, in order to monitor changes in acid production. The adenylate cyclase
      inhibitor, alloxan, blocked parathyroid hormone (PTH)-stimulated acid production.
      Dibutyryl cyclic adenosine monophosphate, a membrane-permeant form of cyclic
      adenosine monophosphate, mimicked the PTH effect. Bisindolylmaleimide, a specific
      inhibitor of protein kinase C (PKC), blocked the initial stimulation (15, 30, and
      60 min) of acid production by PTH but had no effect on long-term stimulation (120
      min). Confocal microscopy of osteoclasts stained with fluorescein-conjugated
      bisindolylmateimide revealed a shift in location of PKC from the cytoplasm to the
      plasma membrane region after treatment with parathyroid hormone. The results of
      these studies support the hypothesis that PTH regulation of acid production in
      osteoclasts involves both adenylate cyclase and PKC as effectors.

PMID- 9178106
TI  - Heparan sulfate-binding peptide promotes the deposition of proteoglycans in the
      extracellular matrix.
AB  - A synthetic peptide, which was shown to bind extracellular matrix heparan sulfate
      chains with a high degree of affinity and specificity [Colburn et al. (1996):
      Arch Biochem Biophys 325:129-138], has now been found to promote the transfer and
      the deposition of endothelial cell surface proteoglycans in the extracellular
      matrix. The peptide also induces preferential binding of extracellular matrix
      heparan sulfate proteoglycans, which have been added to the supernatant growth
      medium, and the requirement for its presence is stringent in that only a
      negligible amount of proteoglycans are bound to the cell layer in the absence of
      the peptide. In addition, antibodies directed against the peptide detect the
      accumulation of the peptide in the matrix compartment where the peptide is found
      associated with the proteoglycans transferred from the cell surface. The sequence
      of events induced by the peptide appears to be an extension of a naturally
      occurring process since proteoglycans with properties similar to those of the
      species ordinarily present in the extracellular matrix have been observed to
      transfer from the cell surface to the matrix during a pulse-chase experiment. We
      suggest that formation of the complex peptide-proteoglycan with consequent
      displacement of the proteoglycan from its anchorage on the cell initiates the
      process of transfer of the heparan sulfate-bound peptide from the cell surface to
      the extracellular matrix.

PMID- 9178107
TI  - Reactive oxygen species and antioxidants in inflammatory diseases.
AB  - This paper aims to review the role of free radical-induced tissue damage and
      antioxidant defence mechanisms in inflammatory diseases that involve pathogenic
      processes similar to the periodontal diseases. There is a clearly defined and
      substantial role for free radicals or reactive oxygen species (ROS) in
      periodontitis, but little research has been performed in this area. This paper
      reviews the considerable data available relating ROS activity and antioxidant
      defence to inflammatory diseases and attempts to draw parallels with
      periodontitis, in an effort to stimulate more periodontal research in this
      important area. The recent discovery of the transcription factor nuclear factor
      kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine
      induced periodontal tissue damage, mediated by NF-kappa B1 are discussed.
      Emphasis is placed on cytokines that have been studied in periodontitis,
      principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between
      cellular production of such important mediators of inflammation and the
      antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and
      it is hypothesised that NF-kappa B antagonists may offer important therapeutic
      benefits.

PMID- 9178108
TI  - Cytokines modulate routes of collagen breakdown. Review with special emphasis on
      mechanisms of collagen degradation in the periodontium and the burst hypothesis
      of periodontal disease progression.
AB  - In this paper, we review recent work on collagen degradation, 2 main routes of
      breakdown are described and their relevance during healthy and inflammatory
      conditions of the periodontium is discussed. Special attention is paid to the
      possible role of cytokines, in particular interleukin 1 (IL-1) and transforming
      growth factor beta (TGF-beta), on the modulation of collagen phagocytosis and
      metalloproteinase production. IL-1 has been shown to have a dual function in
      collagen digestion. It inhibits the intracellular phagocytic pathway, but at the
      same time, it strongly promotes extracellular digestion by inducing the release
      of collagenolytic enzymes like collagenase. TGF-beta has an opposite effect on
      both pathways and antagonizes IL-1. Collagenase is released in an inactive form,
      and a considerable fraction of the proenzyme may become incorporated in the
      extracellular matrix. This reservoir of latent enzyme can be activated (for
      instance by plasmin), leading to a sudden and extensive breakdown of the
      collagenous fibre meshwork. It is suggested that this phenomenon may also take
      place during progressive periodontitis and could explain an episodic nature of
      collagenolysis, clinically resulting in bursts of attachment loss (burst
      hypothesis).

PMID- 9178109
TI  - Marginal bone level buccal to mandibular molars in digital radiographs from
      charge-coupled device and storage phosphor systems. An in vitro study.
AB  - The aim of this in vitro study was to compare bone loss measurements in the
      furcation area of mandibular molars in digital radiographs from a CCD-(Sens-A
      Ray) and a storage phosphor (Digora) system, 10 1st and 7 2nd mandibular molars,
      with intact lingual but reduced buccal bone with furcation involvements, were
      used. Radiographs were first taken with lead markers at the most apical part of
      the buccal bone and at the cemento-enamel junction. These radiographs were used
      to establish a radiographically true distance between the CEJ and the buccal bone
      level. The lead marker at the CEJ served as a reference point for the observers'
      subsequent estimates of the extent of bone removed, which were made in
      radiographs without lead markers at the bone level. 1 exposure (400 ms) for the
      CCD- and 5 (160 ms, 200 ms, 250 ms, 320 ms, 400 ms) for the storage phosphor
      system were used. Measurements were made in unprocessed (original) and processed
      images (contrast enhanced and/or high pass filtered). The results showed
      underestimation of bone loss, but smaller than previously reported for film
      radiographs. No significant difference was found between the 2 systems when
      compared at the same exposure. Nor were any significant differences found between
      unprocessed and processed images or between storage phosphor images from
      different exposures. We conclude that digital radiographs are comparable to film
      based radiographs for measurement of buccal bone loss but that lower exposures
      can be used, especially with the storage phosphor system.

PMID- 9178110
TI  - Clearance of sodium lauryl sulphate from the oral cavity.
AB  - Sodium lauryl sulphate (SLS) is used in toothpaste and mouth rinses as an
      emulsifying and surface cleaning agent. SLS has been implicated in an increased
      incidence of oral irritation in subjects predisposed to recurrent aphthous
      stomatitis (RAU). Hence, the purpose of this study was to determine the levels of
      SLS found in the oral cavity following rinsing with an SLS containing mouth rinse
      and brushing with a SLS containing dentifrice. An analytical method to separate
      SLS from saliva and other complex systems was developed. The method used high
      performance liquid chromatography (HPLC) and detection performed using
      conductivity measurements. Standard curves with known concentrations showed a
      detection limit of less than 0.4 ug SLS/ml of fluid. 2 clinical studies were
      conducted to determine the amount of SLS retained in the mouth by a healthy
      population after rinsing or brushing with commercially available products. The
      results showed, after rinsing, that 96% of the available SLS from the rinse was
      recovered in the collected samples within 2 min. Similarly, after brushing, 86%
      of the SLS contained within the toothpaste was recovered from the collected
      samples within the first 10 min. These results showed that the amount of SLS
      retained in the oral cavity was minimal and the contact time between SLS and the
      oral cavity was very short. A 2nd study was conducted to measure the amount of
      SLS retained in the mouth by a population susceptible to RAU. After rinsing, 97%
      of the available SLS was recovered within the first 2 min. Following brushing,
      89% of the SLS in the dentifrice was recovered within the first 10 min. These
      results were comparable to those determined by the study involving the healthy
      population.

PMID- 9178111
TI  - In vitro effect of the Sensonic toothbrush on Treponema denticola.
AB  - The purpose of this in vitro study was to compare the effects of the Sensonic.
      Oral-B Braun mechanical and Oral-B manual toothbrushes upon the morphology and
      cellular integrity of Treponema denticola. This spirochete was chosen because of
      its frequent isolation from active lesions of inflammatory periodontal disease
      and its pathogenic potential. T. denticola, strain ATCC 33421, was grown in an
      anaerobic nitrogen rich atmosphere in enhanced 1186 mycoplasma broth. 160, 5-ml
      aliquots of cultured microbes were assigned to 1 of 3 brushing treatment groups
      and a control group. Samples were further divided into 4 groups of 10 samples
      each and assigned to one of 4 brushing exposure times: 15, 30, 45, and 60
      seconds. After treatment, 0.2 ml of each sample was applied to a millipore filter
      and examined by SEM. Intact microbes were counted from 10 non-overlapping fields
      at 4500x. Remaining treated samples were pelleted and examined by TEM. A
      statistically significant reduction of intact microbes for the Sensonic treatment
      group at each exposure time was found when compared to Oral-B Braun, Oral-B
      manual, and non-treated controls. TEM examination of Sensonic treated samples
      revealed separation of the outer membrane at lower exposure times and only
      cellular debris after exposures of 45 and 60 s. These results suggest that
      exposure to the sonic frequency generated by the Sensonic toothbrush is capable
      of severely disrupting the structural integrity of T. denticola.

PMID- 9178113
TI  - Self-concept and dental health behaviours in adolescents.
AB  - The purpose of this investigation was to examine the relation between some dental
      health behaviours and 2 measures of self-concept in adolescents. Data from a
      survey of 41142, 12-16-year-old children from 244 secondary schools throughout
      England were analysed to obtain information about their frequencies of
      toothbrushing, use of dental floss and dental attendance, and whether they
      recalled advice about toothbrushing, in relation to self-esteem and health locus
      of control (HLOC). Subjects completed a questionnaire, anonymously, in school
      class. The results showed a significant positive correlation (Spearman) between
      the frequencies of flossing and toothbrushing, in both sexes, and between social
      group and toothbrushing frequency, where brushing frequency increased as socio
      economic status improved. Some association between use of floss and social group
      emerged, but this was smaller and less consistent than that observed with
      toothbrushing brushing frequency. Self-esteem was positively correlated with
      toothbrushing frequency at ages 12-15 years, while HLOC showed correlations at
      some ages but not others. Use of dental floss showed no relation to self-concept.
      Subjects with more favourable self-concept were more likely to make more frequent
      dental visits than those with a poorer self-view. There was a strong and
      consistent correlation between recalled advice about toothbrushing and lower self
      esteem and external locus of control. The results are in agreement with our
      earlier reports and suggest that self-concept may play a significant role in
      mediating changes in dental health behaviour.

PMID- 9178112
TI  - The effect of SRP on the clinical and microbiological parameters of periodontal
      diseases.
AB  - The purpose of the present investigation was to examine the effect of SRP on
      clinical and microbiological parameters in 57 subjects with adult periodontitis
      (mean age 47 +/- 11 years). Subjects were monitored clinically and
      microbiologically prior to and 3, 6 and 9 months after full-mouth SRP under local
      anaesthesia. Clinical assessments of plaque, redness, suppuration, BOP, pocket
      depth and attachment level were made at 6 sites per tooth. The means of duplicate
      attachment level measurements taken at each visit were used to assess change
      between visits. Clinical data were averaged within each subject and then averaged
      across subjects for each visit. Subgingival plaque samples were taken from the
      mesial aspect of each tooth and the presence and levels of 40 subgingival taxa
      were determined using whole genomic DNA probes and checkerboard DNA-DNA
      hybridization. The mean levels and % of sites colonized by each species
      (prevalence) was computed for each subject at each visit. Differences in clinical
      and microbiological parameters before and after SRP were sought using the
      Wilcoxon signed ranks test or the Quade test for more than 2 visits. Overall,
      there was a mean gain in attachment level of 0.11 +/- 0.23 mm (range -0.53 to
      0.64 mm) 3 months post-therapy. There was a significant decrease in the % of
      sites exhibiting gingival redness (68 to 57%) and BOP (58 to 52%) as well as a
      mean (+/-SEM) pocket depth (3.3 +/- 0.06 to 3.1 +/- 0.05 mm). Sites with pre
      therapy pocket depths of < 4 mm showed a non-significant increase in pocket depth
      and attachment level, 4.6 mm pockets showed a significant decrease in pocket
      depth and a non-significant gain in attachment post-therapy, while > 6 mm pockets
      showed a significant decrease in pocket depth and attachment level measurements
      post-therapy. Significant clinical improvements were seen in subjects who had
      never smoked or were past smokers but not in current smokers. Mean prevalences
      and levels of P. gingivalis, T. denticola and B. forsythus were significantly
      reduced after SRP, while A. viscosus showed a significant increase in mean
      levels. The mean decrease in prevalence of P. gingivalis was similar at all
      pocket depth categories, while B. forsythus decreased more at shallow and
      intermediate pockets and A. viscosus increased most at deep sites. P. gingivalis.
      B. forsythus and T. denticola were equally prevalent among current, past and
      never smokers pre-therapy, decreased significantly post-SRP in never and past
      smokers but increased in current smokers. Clinical improvement post-SRP was
      accompanied by a modest change in the subgingival microbiota, primarily a
      reduction in P. gingivalis, B. forsythus and T. denticola, suggesting potential
      targets for therapy and indicating that radical alterations in the subgingival
      microbiota may not be necessary or desirable in many patients.

PMID- 9178114
TI  - In vitro accuracy and reproducibility of automated and conventional periodontal
      probes.
AB  - The aim of this study was to investigate the accuracy and reproducibility of
      experienced and inexperienced examiners using 3 automated periodontal probes
      (Florida Pocket Probe, Florida Disk Probe, Peri Probe) in comparison with 3
      conventional periodontal probes (Marquis, Williams and EN-15 probes). Test blocks
      of aluminium had 30 holes of diameter 1.10 mm and depths ranging from 2.75 to
      10.0 mm. machined with a tolerance of +/- 0.01 mm. 8 experienced examiners and 8
      inexperienced examiners were selected to perform duplicate measurements on the
      blocks over 6 visits using each of the 6 probes. 1 automated and 1 conventional
      probe were used at each examination. The % accuracy and reproducibility for each
      of the duplicate measurements was calculated and analysed using Friedman 2-way
      analysis of variance and the Wilcoxon matched pairs test. On average, all probes
      showed high reproducibility, with the Florida Disk Probe, the Florida Pocket
      Probe and the Williams probe ranked best and the other 3 probes were less
      reproducible. On average, all probes showed a high degree of accuracy, automated
      probes were ranked best and were significantly better than conventional probes.
      Experience had little effect on reproducibility, with only the Peri Probe showing
      significant differences at the 5% level between the groups. Experience appeared
      to be more important for accuracy, as experienced examiners were more accurate
      than inexperienced examiners, with significant differences at the 5% level for
      the EN-15, Florida Disk Probe and Peri Probe. However, inexperienced examiners
      were significantly more accurate using the Williams probe. This in vitro study
      has shown that automated probes offer increased accuracy over conventional probes
      and the Florida Pocket and disk probes compare well with conventional probes for
      reproducibility.

PMID- 9178115
TI  - Protein degradation by Prevotella intermedia and Actinomyces meyeri supports the
      growth of non-protein-cleaving oral bacteria in serum.
AB  - The proteolytic activities of oral bacteria are thought to play an important role
      in the aetiology of dental abscesses. Bacteria-derived proteases may contribute
      to tissue destruction, and are likely to impair host defence by degrading
      immunoglobulins and complement. Degraded periodontal tissue and tissue fluid are
      likely to constitute essential sources of nutrients in the abscess. Tissue fluid,
      which is derived from serum, is rich in protein and poor in carbohydrate,
      suggesting that breakdown of protein and fermentation of amino acids is a crucial
      step to generate energy for growth of the microflora. The number of oral
      bacterial species that perform hydrolytic cleavage of protein into polypeptides,
      the first step in protein degradation, is relatively small compared to the large
      majority of peptidase-producing species. In this study, we therefore investigated
      the growth-promoting effect of proteinase-producing species like Prevotella
      intermedia and Actinomyces meyeri on the growth of some non-proteinase producing
      bacteria in mixed cultures. We used serum as a substitute for the supposed
      natural substrate of the abscess microflora. The breakdown of serum proteins was
      investigated using capillary electrophoresis. Poor growth was found in mono- and
      mixed cultures of non-proteinase producing species Eubacterium lentum,
      Fusobacterium nucleatum. Peptostreptococcus micros, and Streptococcus
      intermedius. The presence of P. intermedia in mixed cultures strongly enhanced
      growth of these 4 species, according to the hypothesis that the growth of the
      mixed cultures was peptide-limited. The enhanced growth of P. intermedia in
      pronase-digested serum indicated peptide-limited growth of this organism in
      serum, despite its production of proteinase. We found that growth of monocultures
      of Actinomyces meyeri was poor. In contrast, A. meyeri grew well in mixed
      cultures and its presence stimulated growth of F. nucleatum and P. micros,
      suggesting a synergistic relationship. The growth of mono- and mixed cultures was
      investigated using one representative strain of each species. Thus, there is a
      small risk of having selected unique strains. Proteinase inhibitors reduced the
      growth of Porphyromonas gingivalis, Prevotella nigrescens, and P. intermedia in
      trypticase peptone-yeast extract medium with, and without, IgG. Our study
      indicated that proteinase-producing organisms play a key role in mixed cultures
      of oral bacteria in human serum by providing polypeptides for growth. This may
      explain their association with dental abscesses.

PMID- 9178116
TI  - The impact of the closing of three Massachusetts public chronic disease
      hospitals: a multidimensional perspective.
AB  - The closing of three public chronic disease hospitals in Massachusetts in 1991 as
      a cost-cutting measure sparked renewed attention to the consequences of
      relocation. Massachusetts officials faithfully carried out a series of measures
      to assure that patients would be transferred to facilities providing high quality
      care and that the relocation process would be highly sensitive to patient needs.
      A survey of family representatives revealed that both the relocation process and
      the outcome tended to be perceived positively. Quasi-experimental studies of
      health and survival outcomes, however, provided less favorable results. On two of
      three measures of health change, relocation was found to have no effect. However,
      relocation was found to increase the likelihood of incontinence. For patients at
      the hospital with the greatest concentration of older patients, relocation lead
      to heightened mortality rates. Also disappointing for State officials was the
      fact that the anticipated cost savings were less than anticipated. The findings
      point to the need for renewed efforts to understand the circumstances when
      relocation places institutionalized older people at serious risk, more careful
      cost estimates of the savings to be achieved through proposed cost-saving policy
      changes, and more carefully formulated policy guidelines for relocation of the
      institutionalized elderly that balance the risks associated with relocation
      against other public policy objectives.

PMID- 9178117
TI  - Skin cancer prevention: a time for action.
AB  - Skin cancer is the most common malignancy in the United States accounting for
      more than 840,000 cases and 9,400 deaths annually. It is estimated that 90% of
      non-melanoma skin cancers and much of melanoma incidence can be attributed to sun
      exposure. The evidence suggests that regular use of sunscreen (Sun Protective
      Factor (SPF) of 15 or higher), wearing protective, tightly woven clothing and
      wide brimmed hats, and avoiding sun exposure when the ultraviolet rays are
      strongest (between 11:00 a.m. and 3:00 p.m.) can dramatically reduce the risk of
      skin cancer. Interventions to promote sun-protection behaviors that target
      children and adults are necessary to reduce the growing incidence rate of skin
      cancer in the United States.

PMID- 9178118
TI  - Survey of condom-related beliefs, behaviors, and perceived social norms in
      Mexican migrant laborers.
AB  - This study reports findings from a survey of condom-related beliefs, behaviors,
      and perceived social norms in Mexican migrant laborers that live and work in the
      United States for extended periods of time. Snowball sampling was used to recruit
      501 Mexican migrants from five "sending towns" in Jalisco, Mexico, with
      historically high rates of out-migration to the United States. Results showed
      that subjects reported few negative beliefs about condom use and high efficacy to
      use condoms in challenging sexual situations but social norms sanctioning condoms
      were limited. Results also revealed mixed knowledge of HIV transmission, poor
      knowledge of condom use, and higher condom use with occasional versus regular sex
      partners. Forty-four percent of male migrants reported sex with prostitutes while
      in the U.S., with married men reporting less condoms use with prostitutes than
      single men. It was concluded that condom promotion efforts with Mexican migrants
      should concentrate on men to encourage consistent use with occasional sex
      partners, including prostitutes. AIDS prevention education should be provided
      with sensitivity to the language needs, limited education, and extreme social and
      geographic marginality of this highly underresearched Latino population.

PMID- 9178119
TI  - An examination of differential follow-up rates in cervical cancer screening.
AB  - The purpose of this study was to test the hypothesis that follow-up rates for
      women with abnormal cervical cancer screening results vary by age, ethnicity, and
      initial screening results in California's Breast and Cervical Cancer Control
      Program. The sample consisted of women in the screening program who received an
      abnormal cervical screening result (N = 1.738). Bivariate and logistic regression
      analyses were utilized to examine variables that account for differences in
      follow-up rates among these women. Bivariate analysis showed significant
      differences by age, race/ethnicity, initial screening results, and urban/rural
      residence. In logistic regression analysis, these variables also retained
      significance. Severity of diagnosis was a highly significant predictor of follow
      up. Women of color, older women, and women with less severe diagnoses should be
      targeted as groups needing assistance in adhering to follow-up recommendations.

PMID- 9178120
TI  - Overweight and obesity in Saudi Arabian adult population, role of socio
      demographic variables.
AB  - The objectives of this Community-based National Epidemiological Household Survey,
      conducted between 1990-1993, were to estimate the prevalence of overweight and
      obesity in Saudi Arabia and to examine its association with the socio-demographic
      characteristics of the adult population. A sample of Saudis 20 years and over was
      selected using a multistage stratified cluster sampling technique with
      probability proportionate to size. The selected subjects were requested to visit
      primary health care centers in their localities. Physicians in these clinics took
      measurements of heights and weights and collected other relevant data. Obesity
      was measured by the Body Mass Index, using the Quetelet Index. The results showed
      the sample of 10,651 subjects of which 50.8% were males, had a mean age of 35.8
      years (SD = 14.27 years). The prevalence of overweight was 31.2% (95% confidence
      interval: 30.3%, 32.1%); 33.1% for males and 29.4% for females. For obesity, the
      overall prevalence was 22.1%; males 17.8% and females 26.6%. The study design
      suggested that these estimates could be closer to the true values. The multiple
      logistic regression analysis showed that age, residential area, region, income,
      gender, and education are statistically significant predictors of obesity. The
      prevalence of obesity was higher in females than males, lower in subjects living
      in rural areas with traditional lifestyles than those in more urbanized
      environments, and increased with increasing age. The observed prevalence and
      pattern of overweight and obesity with age and gender is similar to those
      observed in the Arab community and some Western nations. There is a need for
      increased physical activity and better nutrition education programs to reduce the
      extent of obesity and to prevent the serious health consequences, especially, in
      the middle age group.

PMID- 9178121
TI  - Bovine somatotropin dose titration in lactating dairy ewes. 2. Dose determination
      and factors affecting the response.
AB  - Seventy-four lactating dairy ewes were injected with recombinant bovine
      somatotropin (bst; sometribove) in a sustained-release formulation. Ewes received
      0, 80, 160, or 240 mg of bST/14 d from wk 3 to 8 of lactation (part 1) and 0, 80,
      or 160 mg of bST/14 d from wk 11 to 18 of lactation (part 2). The optimal dose of
      bST was studied as well as the factors (lactation stage, lactation number,
      initial milk production, body weight, and body condition) possibly affecting the
      increase in milk production following bST injection. Using a quadratic regression
      model, the maximum theoretical dose was determined to be 181 mg of bST/14 d
      during the first part of lactation. During the second part of lactation, 143 mg
      of bST/14 d was the maximum theoretical dose. The increment of milk production
      did not vary with lactation number, but first lactation ewes, in general,
      responded better than did multiparous ewes. Relative to initial milk production,
      improvement was greatest for ewes with average milk production (1500 ml/d) that
      received a dose of 192.3 mg of bST/14 d during the first part of lactation;
      improvement was also measured from the highest producers (2000 ml/d) during the
      second part of lactation. The best response was obtained from ewes with average
      body condition (score 3 on a five-point scale where 1 = thin to 5 = fat) and a
      dose of 200 mg of bST/14 d during the first part of lactation; during the second
      part of lactation, body condition score had no effect. Body weight had no effect
      on the increment of production at any time.

PMID- 9178122
TI  - Effects of monensin on the metabolism of periparturient dairy cows.
AB  - The effects of monensin on plasma concentrations and changes in plasma
      concentrations of energy metabolites and minerals over time were investigated
      using 24 multiparous Holstein cows. Cows were paired according to farm, predicted
      date of calving, and body condition score and were randomly allocated to two
      groups. Treated cows were given a ruminal bolus containing 32 g of monensin at 50
      +/- 7 d before predicted calving. Treated cows had lower plasma concentrations of
      glucose, free fatty acid (FFA), and beta-hydroxybutyrate (BHBA) than did control
      cows before calving, indicating that monensin influenced energy metabolism.
      However, no significant differences in plasma concentrations of glucose, FFA, and
      BHBA were found between groups after calving. Plasma BHBA concentrations
      increased more before calving in control cows, and plasma FFA and urea
      concentrations increased significantly before calving in all cows. No significant
      differences in body weight, plasma concentrations of urea, or whole blood
      concentrations of glutathione peroxidase were detected between groups before or
      after calving. Plasma ceruloplasmin activity did not differ between groups before
      calving, but was significantly higher in treated cows after calving. Plasma
      concentrations of Ca did not significantly differ between groups before or after
      calving. Monensin altered both energy and mineral metabolism and has the
      potential to improve the health and production of dairy cows.

PMID- 9178123
TI  - Composition of colostrum from dairy heifers exposed to high air temperatures
      during late pregnancy and the early postpartum period.
AB  - This study examined the effects of heat stress on composition of colostrum from
      primiparous cows during late pregnancy and the early postpartum period. Two
      groups of 6 Holstein heifers were utilized. During the last 3 wk of pregnancy and
      during the first 36 h after calving, one group was exposed to thermal comfort
      (temperature-humidity index = 65); the other group was exposed to high air
      temperatures (temperature-humidity index = 82 from 0900 to 2000 h and temperature
      humidity index = 76 from 2100 to 0800 h). Heifers under heat stress had higher
      rectal temperatures and respiratory rates; lower plasma triiodothyronine and
      glucose; higher plasma nonesterified fatty acids and beta-hydroxybutyrate; lower
      intakes of dry matter, net energy for lactation, and crude protein; higher water
      intakes; and lower body condition scores. The decline of plasma immunoglobulins
      (Ig) over the final 2 wk of pregnancy was less pronounced for heifers under heat
      stress. For the first four milkings, colostrum of cows exposed to high air
      temperatures had lower mean concentrations of IgG and IgA; lower mean percentages
      of total protein, casein, lactalbumin, fat, and lactose; lower contents (grams
      per liter) of short- and medium-chain fatty acids; lower energy; lower titratable
      acidity; and higher pH. Thus, high air temperatures during late pregnancy and the
      early postpartum period markedly affected the composition of colostrum from
      primiparous dairy cows.

PMID- 9178124
TI  - Field trials of a vaccine against bovine mastitis. 1. Evaluation in heifers.
AB  - A vaccine was developed against bovine mastitis based on inactivated, highly
      encapsulated Staphylococcus aureus cells; a crude extract of Staph. aureus
      exopolysaccharides; and inactivated, unencapsulated Staph, aureus and
      Streptococcus spp. cells. This vaccine was tested on 30 heifers during a 7-mo
      period. The 30 heifers were randomly assigned to three groups of 10 heifers each.
      The prepartum group received two injections of the vaccine at 8 and 4 wk before
      calving, and the postpartum group received two injections at 1 and 5 wk after
      calving. The control group received two injections of a placebo at 8 and 4 wk
      before calving. The vaccine or the placebo was administered subcutaneously in the
      brachiocephalicus muscle of the neck. The frequencies of intramammary infections
      caused by Staph. aureus were reduced from 18.8% for heifers in the control group
      to 6.7 and 6.0% for heifers in the prepartum and postpartum groups, respectively.
      This protective effect was maintained for at least 6 mo. The relative risk of
      mastitis caused by Staph. aureus was 0.31 and 0.28 for heifers in the prepartum
      and postpartum groups, respectively, compared with that for heifers in the
      control group. The results of the trial indicated the effectiveness of the
      vaccine in decreasing the incidence of intrammammary infections caused by Staph.
      aureus. A slight but nonsignificant increase occurred in fat production in the
      milk of vaccinated cows. The vaccine had no observable effect on somatic cell
      count or streptococcal infections.

PMID- 9178125
TI  - Field trials of a vaccine against bovine mastitis. 2. Evaluation in two
      commercial dairy herds.
AB  - A vaccine against bovine mastitis was developed. The vaccine was based on
      inactivated, highly encapsulated Staphylococcus aureus cells; a crude extract of
      Staph. aureus exopolysaccharides; and inactivated unencapsulated Staph. aureus
      and Streptococcus spp. cells. In this study, the vaccine was evaluated in 164
      cows from two commercial dairies (A and B) during a 4-mo period. Two doses of the
      vaccine were administered subcutaneously to 82 cows in the brachiocephalicus
      muscle of the neck within a 4-wk interval. The results of this trial revealed
      significantly fewer intramammary infections caused by Staph. aureus at various
      levels of severity (clinical, subclinical, and latent) in cows that were
      vaccinated. The odds ratios of all types of intrammammary infections caused by
      Staph. aureus for dairies A and B, which were determined by a logistic model,
      were 1.84 and 1.89, respectively, for quarters of vaccinated cows and quarters of
      control cows. The colony counts for Staph. aureus in milk from infected quarters
      of vaccinated cows were significantly lower than those in milk from infected
      quarters of control cows. Also, the somatic cell counts per milliliter in milk
      from vaccinated cows were significantly decreased when the initial somatic cell
      count was < 500,000 cells/ml at the start of the trial. The vaccine had no
      observable effect on fat production in milk or on streptococcal infections.

PMID- 9178126
TI  - The effects of early antibiotic treatment following diagnosis of mastitis
      detected by a change in the electrical conductivity of milk.
AB  - Mastitis was induced experimentally by infusion of Streptococcus uberis or
      Staphylococcus aureus into the mammary glands of lactating dairy cows. Clinical
      mastitis was identified when clots appeared in foremilk (conventional diagnosis)
      or was predicted by changes in the electrical conductivity of foremilk (early
      diagnosis). The responses to intramammary antibiotic treatment that was initiated
      after early diagnosis of mastitis and after conventional diagnosis were compared.
      Early treatment significantly limited the severity of the disease and, in many
      cases, prevented the appearance of any visible signs of infection. Milk yield was
      less depressed, and the somatic cell count (SCC) was lower, when treatment was
      initiated earlier. The SCC of the quarter at the time mastitis was predicted was
      approximately 2 x 10(6) cells/ml for both pathogens, which was significantly less
      than when clots appeared at conventional diagnosis, approximately 4 x 10(6) and
      12 x 10(6) cells/ml for Staph. aureus and Strep. uberis, respectively. The time
      required for SCC to recover to < 4 x 10(5) cells/ml was significantly less,
      approximately half, for both pathogens following early detection and early
      initiation of treatment. When treatment was administered in response to early
      detection, the bacteriological and clinical cure was almost complete, and the
      amount of antibiotic used was < or = 50% less. Obvious benefits for milk yield
      and quality and the health of the cow would result when changes in the electrical
      conductivity of milk are used to predict clinical mastitis and when treatment is
      initiated early.

PMID- 9178127
TI  - Evaluation of alternative equations for prediction of intake for Holstein dairy
      cows.
AB  - Six prediction equations for dry matter intake (DMI) were evaluated for accuracy
      with independent data. The equations were selected based on ease of parameter
      measurement and practical on-farm use. The equations were assessed for accuracy
      of predicting individual weekly DMI for primiparous (n = 105) and multiparous (n
      = 136) cows; three-fourths of these cows were supplemented with a sustained
      release form of bovine somatotropin (bST). Large variations in accuracy were
      identified across the six prediction equations for effects of parity and bST.
      Prediction accuracy of all equations for cows in wk 1 to 24 of lactation was
      better for primiparous cows than for multiparous cows. Precision of prediction
      equations was poor for cows in wk 8 through 12 of lactation and for cows in > 40
      wk of lactation. The equation for DMI with the best accuracy measured by a low
      total lactation mean square prediction error was the modified equation of the
      National Research Council: DMI (kilograms per day) = -0.293 + 0.372 x fat
      corrected milk (kilograms per day) + 0.0968 x body weight 0.75 (kilograms).
      However, the overall mean bias (predicted minus observed) of the prediction of
      weekly DMI of a single cow was high for all equations, including the modified
      equation of the National Research Council. For wk 2, 4, 8, 10, and 20 of
      lactation, the mean bias for the modified equation was +6, +3.4, -1.3, -2.1, and 
      2.8 kg/d. The accuracy of prediction was lower for cows treated biweekly with
      bST. High yielding cows and cows treated biweekly with bST had higher milk yields
      in relation to body weight, and standardized prediction equations for DMI were
      less accurate.

PMID- 9178128
TI  - Development and evaluation of equations for prediction of feed intake for
      lactating Holstein dairy cows.
AB  - Improved prediction equations for dry matter intake (DMI) of Holstein cows that
      consume high energy diets were developed using regression techniques applied to a
      comprehensive database. The equations for predicting DMI, which were dependent on
      parity, accounted for the effects of milk yield, milk protein, body weight (BW),
      BW change, days pregnant, ambient temperature, relative humidity, and night
      cooling. A simplified prediction equation of DMI for farm application was
      developed and based on milk protein yield and BW at calving. An ambient
      temperature and a lag adjustment factor for early lactation were developed to
      improve accuracy of prediction of DMI of dairy cows in early lactation. The
      developed equations for DMI were evaluated against six independent data files.
      These equations accounted for 55 to 98% of the variation of the weekly group DMI
      of the independent validation data. The remainder of the variation in intake was
      attributed to diet, management, and undescribed animal factors. The equations
      developed in this study had a mean proportional bias of 5.6% and a mean square
      prediction error of 5.45 kg2/d. Predicted intake using the new equations was
      within 3 to 8% of actual intake. The new equations must be applied to situations
      in which Holstein dairy cows are fed highly digestible diets because dietary fill
      effects are not considered in these equations. The relationship of milk protein
      yield and DMI warrants further investigation.

PMID- 9178129
TI  - Dietary variety via sweetening and voluntary feed intake of lactating dairy cows.
AB  - The effects of choice of diets on feed intake were studied using 12 lactating
      Holstein cows. A switchback design was used that had three periods and two
      sequential blocks. Diets were 1) a control total mixed ration (TMR), which
      consisted of alfalfa haylage, corn silage, and a concentrate mixture based on
      ground corn and soybean meal (25:25:50 on a dry matter basis) and 2) a sweetened
      TMR in which a brown sugar food product constituted 1.5% of the dietary dry
      matter. Treatments consisted of the control TMR fed on both sides of divided feed
      bunks, the sweetened TMR fed on both sides of divided feed bunks, or both TMR fed
      on alternating (daily) sides of divided feed bunks in tie stalls. Periods were 2
      wk in duration, and cows averaged 67 and 53 d of lactation at the start of blocks
      1 and 2, respectively. The dry matter intake, body weight, milk yield, and
      percentages of milk fat, protein, and solids not fat were similar when either TMR
      was fed alone. A choice of control TMR or sweetened TMR did not affect any of
      these variables. The dry matter intake, body weight, milk yield, and milk protein
      percentage were affected by block; however, these effects were probably caused by
      differences between the blocks in environment and stage of lactation. The results
      of this experiment might have been affected by the composition of the control
      TMR, its similarity to the sweetened TMR, availability of both diets
      simultaneously when a choice was offered, and use of a TMR instead of separate
      feeds or simpler mixtures.

PMID- 9178130
TI  - Influence of particle size on the effectiveness of beet pulp fiber.
AB  - Sixteen Holstein cows in midlactation were used in a design based on a replicated
      4 x 4 Latin square with the last period removed to determine the influence of
      particle size of beet pulp neutral detergent fiber (NDF) on its effectiveness as
      a replacement for alfalfa NDF. Diets were a low forage, low fiber diet [12.1 g of
      alfalfa NDF/100 g of dry matter (DM)], a normal forage diet (low forage plus 7.8
      g of additional alfalfa NDF/100 g of DM), and two low forage diets with 5.3 g of
      NDF/100 g of DM from either whole or finely ground dried sugar beet pulp.
      Replacement of alfalfa fiber with beet pulp fiber increased milk protein yield
      because of the tendencies toward increased milk yield and protein concentration.
      However, milk fat concentration and yield were unaffected. The addition of beet
      pulp fiber, either whole or ground, to the basal low forage, low fiber diet did
      not affect yields of milk, protein, or fat, but milk protein concentration tended
      to be lower for cows fed the beet pulp diets than for cows fed the basal diet.
      Reducing the particle size of beet pulp increased DM intake but did not affect
      any of the milk yield measurements. Particle size reduction of beet pulp did not
      reduce its effectiveness as a fiber source as measured by changes in milk fat
      content.

PMID- 9178131
TI  - Effect of percentage of dietary forage neutral detergent fiber and source of
      starch on performance of lactating Jersey cows.
AB  - Five Jersey cows were used in a 5 x 5 Latin square design to determine the
      effects of decreasing dietary forage neutral detergent fiber (NDF) and different
      sources of dietary starch on performance and nutrient digestibilities. The
      control diet was balanced to consist of 21% forage NDF and 43% nonfiber
      carbohydrates. Four other diets were balanced to contain 35% nonfiber
      carbohydrates and either 16 or 11% forage NDF; diets were arranged in a 2 x 2
      factorial design with either corn or corn and wheat as the sources of starch. Dry
      matter intake decreased linearly as forage NDF decreased; however, most of the
      decrease occurred when forage NDF was reduced from 16 to 11%. Milk production,
      yield of 4% fat-corrected milk, and percentages of milk fat and protein were
      similar among diets. Digestibility of NDF and acid detergent fiber increased as
      forage NDF decreased, but fiber digestibilities decreased with the addition of
      wheat to the diets. Starch digestibility was similar among diets. Source and
      amount of starch may be equally important or more important than the percentage
      of forage NDF for maintaining nutrient digestibilities of the total tract. Forage
      NDF in the diets of high producing cows can be reduced to 16% when sources and
      concentrations of starch are adequately balanced.

PMID- 9178132
TI  - Effect of nigericin, monensin, and tetronasin on biohydrogenation in continuous
      flow-through ruminal fermenters.
AB  - Four ionophores differing in cation selectivity were compared for their effect on
      microbial fermentation and biohydrogenation by ruminal bacteria in continuous
      culture. Monensin and nigericin are monovalent antiporters with selective binding
      affinities for Na+ and K+, respectively. Tetronasin is a divalent antiporter that
      binds preferentially with Ca2+ or Mg2+. Valinomycin is a monovalent uniporter and
      does not exchange K+ for H+. Steady-state concentrations of 2 micrograms/ml of
      monensin, nigericin, tetronasin, or valinomycin were maintained by constant
      infusion into fermenters. Molar percentages of acetate were lower, and those of
      propionate were higher, in the presence of monensin, nigericin, and tetronasin;
      all three ionophores also decreased CH4 production. Concentrations of valinomycin
      as high as 8 micrograms/ml had no effect on volatile fatty acids or CH4
      production. Monensin, nigericin, and tetronasin inhibited the rate of
      biohydrogenation of linoleic acid. Continuous infusion of C18:2n-6 at a steady
      state concentration of 314 micrograms/ml into fermenters receiving monensin,
      nigericin, or tetronasin resulted in lower amounts of stearic acid and higher
      amounts of oleic acid. Ionophores increased total C18:2 conjugated acids mainly
      because of an increase in the cis-9, trans-11-C18:2 isomer. If reflected in milk
      fat, ionophore-induced changes in ruminal lipids could enhance the nutritional
      qualities of milk.

PMID- 9178133
TI  - Factors affecting body tissue mobilization in early lactation dairy cows. 1.
      Effect of dietary protein on mobilization of body fat and protein.
AB  - Twenty Holstein cows were fed diets that were formulated with 16 or 19% crude
      protein (CP) that contained, respectively, 6 and 9% ruminally undegradable
      protein (RUP) (dry matter basis) to study the effect of increased RUP on tissue
      mobilization and production parameters. Cows were enrolled in the study from -14
      to 114 d postpartum. Body composition measurements using the D2O dilution
      technique were made at -2, 5, and 12 wk postpartum. Maximum loss of body tissue
      occurred between wk 2 prepartum and wk 5 postpartum during which time cows fed
      both treatments mobilized a mean of 54 kg of body fat and 21 kg of body protein.
      Cows continued to mobilize 18 kg of body fat through wk 12 postpartum, but the
      amount of body protein was unchanged. One unit of change in body condition score
      corresponded to about 40 kg of empty body fat. Partitioning of empty body energy
      between empty body fat and protein indicated that, for each unit of change in
      body energy, 93% was lost or gained as body fat, and body protein accounted for
      only 7%. Increasing RUP in the diet had no effect on the postpartum amounts of
      empty body protein, empty body fat, or empty body energy. Milk production was
      39.8 kg for cows fed the 16% CP diet and 42.4 kg for cows fed the 19% CP diet.
      There was an interaction of treatment by week postpartum. Both dry matter intake
      and milk production were lower during the first 6 wk postpartum but were greater
      thereafter for cows fed the 19% CP diet than for cows fed the 16% CP diet. Milk
      CP percentage was higher (3.08% vs. 2.89%), and milk CP yield tended to be
      greater (1.29 vs. 1.15 kg/d), for cows fed the 19% CP diet.

PMID- 9178134
TI  - Milk production and composition responses to the source of protein supplements in
      diets containing wheat middlings.
AB  - Two 3 x 3 Latin square trials were conducted to determine the effect of the
      source of supplemental protein in diets containing wheat middlings on milk
      production and composition. Cottonseed meal or meat and bone meal was substituted
      for a portion of the soybean meal and provided 24.5% of the total dietary crude
      protein. Trial 1 was conducted during fall 1989, and trial 2 was conducted during
      summer 1993. During trial 1, no differences in production or composition of milk
      were found for primiparous cows fed the various protein supplements. Multiparous
      cows tended to have higher dry matter intakes and produced more milk with lower
      milk fat percentages when fed meat and bone meal than when fed soybean meal or
      cottonseed meal. No differences were found among supplements for other milk
      components or for the production of energy-corrected milk. In trial 2,
      primiparous cows tended to produce more milk, and multiparous cows tended to
      produce less milk, when fed meat and bone meal than when fed soybean meal. No
      differences were found for dry matter intake, milk composition, or production of
      energy-corrected milk. Cottonseed meal was equal to soybean meal in supporting
      milk production. Meat and bone meal tended to support higher productions of milk
      than did soybean meal, but production of energy-corrected milk was similar for
      both.

PMID- 9178135
TI  - Influence of undergradability of protein in the diet on intake, daily gain, feed
      efficiency, and body composition of Holstein heifers.
AB  - Thirty-two Holstein heifers with body weights (BW) between 213 and 231 kg were
      randomly assigned to one of four treatments for the 50-d trial. Treatments
      consisted of four percentages of rumen-undegradable protein (RUP) (31, 43, 50,
      and 55% of total N) at 100% of National Research Council recommendations for
      total digestible nutrients and crude protein. Total mixed diets composed of corn
      silage, ground barley straw, soybean meal, blood meal, urea, and minerals were
      formulated for a mean daily BW gain of 0.60 kg. Ration RUP percentage was varied
      by shifting protein sources. Mean dry matter intake (grams per kilogram of
      BW0.75) was 97.6, 84.4, 77.8, and 73.5 for 31% RUP (soybean meal), 43% RUP (blood
      and soybean meal), 50% RUP (blood meal with urea), and 55% RUP (blood meal)
      treatments, respectively. Daily gain was 0.84, 0.89, 0.91, and 0.96 kg/d,
      respectively. Intake of digestible energy (megacalories per kilogram of BW0.75
      per day) was 0.28, 0.24, 0.22, and 0.21, respectively, and feed efficiency
      (megacalories of digestible energy per kilogram of BW gain) was 20.6, 16.1, 15.2,
      and 13.3, respectively. Dry matter intake (grams per kilogram of BW0.75),
      digestible energy intake, feed efficiency, daily BW gain, and hip height differed
      with respect to treatment. There were no differences in growth, wither height, or
      heart girth because of treatments. Changes in percentage of empty body fat as
      estimated by urea space procedures was 6.73, 4.67, 6.67, and 7.32, respectively,
      and did not differ with respect to treatments. These results indicate that
      increasing the RUP percentage in the diets of growing heifers improves feed
      efficiency and increases BW gain.

PMID- 9178136
TI  - Metabolism of water, sodium, potassium, and chlorine by high yielding dairy cows
      at the onset of lactation.
AB  - We studied the balance of Na+, K+, Cl-, and water in six high yielding (> 39 kg/d
      of milk) cows between wk 2 to 1 prepartum and at 2 and 7 wk postpartum during
      winter in Israel. Cows were fed complete diets; Na+ and Cl- contents exceeded
      dietary recommendations, and K+ content was equal to dietary recommendations.
      Milk yield was related positively and significantly to retention of Cl- and K+,
      indicating that ions that are the main constituents of sweat can limit the
      ability of cows to express full genetic potential. The highest ion retention was
      recorded for cows that had the highest dry matter intake and, hence, the highest
      ion intake. Retention of Cl- was highest for cows that were most efficient in
      retaining Cl- in the kidney. In hot climates, increasing the concentrations of
      ions in the diet of early lactation cows according to the actual dry matter
      intake could prevent or reduce the severity of ion deficiencies. Water turnover
      rate of the cows was dependent on dry matter intake, milk yield, and respiratory
      cutaneous water loss. The milk-free water balance (water turnover rate minus
      water secreted in milk) could be very efficiently predicted for lactating and
      nonlactating cows by the following equation: milk-free water balance (kilograms
      per day) = digestible energy intake (megacalories per day) x 0.58 + respiratory
      cutaneous loss (kilograms per day) x 0.97 (n = 18; R2 = 0.97). This formula
      provides a tool to assess the evaporative-cutaneous water loss from feed and
      water intake measurements to evaluate the severity of heat stress.

PMID- 9178137
TI  - Predictability of bull merit from genetic evaluations of sires and maternal
      grandsires using an animal model.
AB  - The ability of animal model evaluations to predict the genetic potential of a
      bull from his sire and maternal grandsire was investigated. Theoretical
      coefficients were derived for different combinations of progeny records on the
      bull, sire, and maternal grandsire. Coefficients > 0.50 for sires and > 0.25 for
      maternal grandsires were associated with bulls with few daughters. Ten animal
      model evaluations of Holsteins, July 1989 to January 1994, were used to estimate
      coefficients realized in three populations: 1) all AI bulls (n = 6924), 2)
      current AI bulls (n = 1344), and 3) elite AI bulls (n = 6116). The PTA were
      analyzed for milk, fat, and protein yields, and for fat and protein percentages.
      Birth year of sons nested within the birth year of their sire was included as a
      random effect with a first-order autoregressive process for the regression model
      used to estimate the realized coefficients for sires and maternal grandsires.
      After adjustment for the genetic trend for estimates of sires, the correlation
      coefficient between predicted merit of sons from 2 consecutive yr ranged from
      0.34 to 0.87. The PTA of bulls from first-crop evaluation were accurately
      predicted from PTA of sire and maternal grandsire for yield and percentage
      traits.

PMID- 9178138
TI  - Dominance models with method R for stature of Holsteins.
AB  - Estimates of variance components were obtained with method R for several additive
      and dominance models. The data included 301,960 records for first parity and
      280,040 records for later parities of Holsteins. The single-record model included
      effects of management, regression on inbreeding percentage, age at calving, stage
      of lactation, and additive and dominance effects. The repeatability model
      included these effects in addition to permanent environment. For the single
      record model, estimates were 46% of the total variance for additive variance, 12%
      of total variance for dominance variance, and -0.06 for the regression
      coefficient on inbreeding. In the repeatability model, the variance for permanent
      environment was estimated at 5%; other estimates were similar. When the dominance
      effect was eliminated, the estimate of the variance for permanent environment
      increased to 17% for the repeatability model. Elimination of stage of lactation
      increased regression on inbreeding to 0.09 and the estimate of dominance variance
      to 17% in the single-record model. The same change increased the estimate of
      additive variance to 64% for the repeatability model. Elimination of regression
      on inbreeding or stage of lactation had a small effect on the estimates. The
      presence or absence of the dominance effect had little influence on additive
      variance. In the absence of dominance, the estimate of the permanent environment
      effect included the dominance effect. Estimates of variances with method R are
      very sensitive to age adjustments. With the adjustments, the estimates of the
      dominance and additive variances are consistent.

PMID- 9178139
TI  - Effects of method of colostrum feeding and colostrum supplementation on
      concentrations of immunoglobulin G in the serum of neonatal calves.
AB  - Holstein heifer and hull calves (n = 52) at Ames Plantation (Grand Junction, TN)
      and Piedmont Research Station (Salisbury, NC) were blocked by sex and assigned
      randomly to receive 3.8 L of maternal colostrum in one feeding, 1.9 L in two
      feedings at a 10- to 12-h interval, or 1.9 L in two feedings at a 10- to 12-h
      interval plus 272 g of colostrum supplement at the first feeding. The colostrum
      supplement was mixed with 0.95 L of warm water and fed immediately following
      colostrum. Serum immunoglobulin G (IgG) concentrations were unaffected by the
      number of feedings and averaged 20.0 and 16.6 g/L at 24 and 48 h, respectively.
      Calves that were fed the colostrum supplement at the first feeding had lower
      serum IgG concentrations at 24 h (16.0 g/L) than did calves that were fed two
      colostrum feedings without supplementation (21.0 g/L); however, serum IgG
      concentrations at 48 h did not differ among treatments. Dry matter intake and
      body weight gain were unaffected by feeding method. Calves may be fed high
      quality colostrum in one or two feedings without affecting IgG absorption.

PMID- 9178140
TI  - Uterine health and disorders.
AB  - Nonspecific uterine infections reduce the reproductive efficiency of cows and the
      profit potential of dairy farms. Fortunately, most cows do not develop severe
      uterine infections. The term uterine infection indicates that the uterus is
      contaminated with pathogenic organisms. Actinomyces pyogenes, either alone or
      with other bacteria, is often associated with uterine infections. When A.
      pyogenes was isolated from uterine fluids after d 21 postpartum, cows developed
      severe endometritis and were infertile at first service. However, the exact
      causes of uterine infections are unknown but are associated with several factors.
      Cows with dystocia, retained placenta, twins or still-births, and various
      metabolic disorders are more likely to develop metritis than are other cows.
      Aberrant immune function before and after calving seems to predispose cows to
      severe uterine infections. Few cows die from uterine infections, but cows with
      uterine infections are more likely to be culled for poor reproductive
      performance. Also, uterine infections can reduce milk production, and some
      treatments contaminate milk. Because they are nonspecific, uterine infections are
      difficult to prevent; attention to sanitation and periparturient hygiene,
      especially during assisted calving, may be the best defense. Evidence that
      aberrant immuno function predisposes cows to uterine infections indicates that
      methods for regulating immune function in periparturient cows have the potential
      for preventing or treating uterine infections.

PMID- 9178141
TI  - Ovarian follicular cysts in dairy cows.
AB  - Ovarian follicular cysts are anovulatory follicular structures that occur in 10
      to 13% of dairy cows. This review focuses upon the dynamics of cyst growth,
      development, and persistence as well as on associated endocrine and cellular
      mechanisms. During the estrous cycle of cows, two to four waves of follicular
      growth occur. From a cohort of recruited follicles, one is selected for continued
      growth and dominance while the other undergo atresia and regress. In contrast,
      cysts have long been thought to be static structures that persist for extended
      periods. Although cysts can persist for extended periods, most regress over time
      and are replaced during subsequent follicular waves. The next dominant follicle
      either ovulates or develops into a new cyst. The recruitment of a cohort of
      follicles from which a cyst develops and the growth rate of cysts to ovulatory
      size are similar to ovulatory follicular waves, but the cyst continues to grow
      for a longer period. The interval between waves of follicular growth is longer
      for cows with cysts than for cows with normal estrous cycles. Each wave is
      preceded by a transient increase in circulating FSH. Near the time of cyst
      development and persistence, the concentration of FSH is not different from that
      during normal estrous cycles. Serum concentrations of LH and estradiol-17 beta
      are higher in cows that develop cysts than in cows that do not. Conversely,
      hypothalamic content of GnRH is lower in cows with cysts. Thus, cysts are dynamic
      structures, and their development and lifespan are likely associated with altered
      hypothalamic-hypophysial-ovarian function.

PMID- 9178142
TI  - Bovine acidosis: implications on laminitis.
AB  - Bovine lactic acidosis syndrome is associated with large increases of lactic acid
      in the rumen, which result from diets that are high in ruminally available
      carbohydrates, or forage that is low in effective fiber, or both. The syndrome
      involves two separate anatomical areas, the gastrointestinal tract and body
      fluids, and is related to the rate and extent of lactic acid production,
      utilization, and absorption. Clinical manifestations range from loss of appetite
      to death. Lactic acid accumulates in the rumen when the bacteria that synthesize
      lactic acid outnumber those that utilize lactic acid. The systemic impact of
      acidosis may have several physiological implications, including laminitis, a
      diffuse aseptic inflammation of the laminae (corium). Although a nutritional
      basis for the disease exists, etiology includes a multitude of interactive
      factors, such as metabolic and digestive disorders, postpartum stress, and
      localized trauma, which lead to the release of vasoactive substances that trigger
      mechanisms that cause degenerative changes in the foot. The severity of laminitis
      is related to the frequency, intensity, and duration of systemic acidotic insults
      on the mechanisms responsible for the release of vasoactive substance. The
      critical link between acidosis and laminitis appears to be associated with a
      persistent hypoperfusion, which results in ischemia in the digit. Management of
      acidosis is critical in preventing laminitis. High producing dairy herds
      attempting to maximize energy intake are continually confronted with subclinical
      acidosis and laminitis. Management of feeding and husbandry practices can be
      implemented to reduce incidence of disease.

PMID- 9178144
TI  - Investigation of the influenza-like symptoms associated with recombinant human
      erythropoietin therapy.
AB  - The mechanism by which fever and influenza-like symptoms occur, after the
      administration of recombinant human erythropoietin (rHuEPO) to patients on
      continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood
      mononuclear cells, obtained from two patients with fever and/or influenza-like
      symptoms related to the administration of rHuEPO for the treatment of anaemia
      were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of
      interleukin-1 beta and tumour necrosis factor-alpha was higher in cultures with
      rHuEPO than in cultures without rHuEPO, although the dose relationships were not
      clear. These findings suggest that increased production of interleukin-1 beta and
      tumour necrosis factor-alpha 1, induced by administration of rHuEPO, may cause
      fever and influenza-like symptoms.

PMID- 9178143
TI  - Effect of the calcium channel blocker nilvadipine on urinary albumin excretion in
      hypertensive microalbuminuric patients with non-insulin-dependent diabetes
      mellitus.
AB  - A 24-week study was conducted to evaluate the effects of the dihydropyridine
      calcium channel blocker nilvadipine on urinary albumin excretion in eight
      microalbuminuric hypertensive patients with non-insulin-dependent (type II)
      diabetes mellitus. Blood pressure and urinary albumin excretion measurements
      before the administration of nilvadipine (8 mg) were compared with those after 4,
      8, 12 and 24 weeks of treatment. No significant changes were observed in the mean
      values of haemoglobin A1C. Systolic blood pressure was significantly reduced from
      174 +/- 23 mmHg before treatment to 144 +/- 13 mmHg after 24 weeks of treatment
      (P < 0.02). Diastolic blood pressure was significantly reduced from 93 +/- 11
      mmHg at baseline to 79 +/- 8 mmHg after 24 weeks of treatment (P < 0.05). Urinary
      albumin excretion was significantly reduced from 65.4 +/- 37.4 mg/g creatinine at
      baseline to 51.6 +/- 41.1 mg/g creatinine (P < 0.05) after 4 weeks, and to 39.1
      +/- 26.9 mg/g creatinine (P < 0.02) after 24 weeks of treatment. These data
      suggest that in hypertensive microalbuminuric patients with non-insulin-dependent
      diabetes mellitus, treatment of hypertension with the calcium blocker nilvadipine
      may slow the progression of diabetic nephropathy.

PMID- 9178145
TI  - A preliminary report on the use of relon mesh in the repair of eventrations with
      large parietal defects. An experimental study in rats.
AB  - This experimental study in rats was designed to investigate the tolerability and
      the mode of healing when commercial relon mesh is used in the repair of large
      abdominal-wall defects. A defect was created to simulate anatomical derangement
      of the abdominal wall and a surgical correction was performed using relon mesh.
      The mesh was implanted intraperitoneally in 18 Wistar albino rats. The animals
      were killed under anaesthesia 4, 6, 8, 12, 15 or 30 days later and the intra
      abdominal viscera were examined macroscopically for adhesions and other evidence
      of inflammatory reactions. Skin healing usually occurred within 7-8 days of
      surgery. Microscopic studies were used to confirm the gross findings and showed
      that maturation of granulation tissue, fibrocyte invasion with encapsulation of
      the mesh and the appearance of newly formed vessels occurred 2 weeks after
      surgery. Within 4 weeks a strong layer of connective tissue was present. The
      relon mesh was tolerated well. These results indicate that the use of relon mesh
      may provide a cheap alternative means of repairing large abdominal-wall defects.

PMID- 9178146
TI  - Role of transforming growth factor-beta 1 and -beta 2 in ddY mouse nephropathy.
AB  - We investigated the glomerular distribution of transforming growth factor-beta
      (TGF-beta 1 and TGF-beta 2) protein and the expression of its mRNA, and related
      factors, in ddY mice, aged 5-60 weeks, before and after the onset of nephropathy,
      TGF-beta 1 protein expression was observed from the age of 20 weeks onwards,
      peaking at 50 weeks, and then declining. Expression of TGF-beta 2 protein
      gradually increased from 5 to 60 weeks. TGF-beta 1 and TGF-beta 2 mRNA were both
      detected from 5 to 60 weeks. The mesangial matrix expansion index (MMEI) was
      significantly higher in mice with nephropathy than in those without nephropathy,
      as was the expression of TGF-beta 1 and TGF-beta 2 proteins (P < 0.05). TGF-beta
      2 was significantly positively correlated with the MMEI (P < 0.05). Infiltration
      of CD68-positive monocytes/macrophages gradually increased until 60 weeks, and
      was significantly correlated with the expression of TGF-beta 1 (P < 0.05) and TGF
      beta 2 (P < 0.01). These findings indicate that TGF-beta 1 and TGF-beta 2 were
      overexpressed in ddY mice with overt nephropathy compared with pre-nephropathic
      mice. TGF-beta 2 may be an important mediator of mesangial matrix expansion in
      ddY mouse nephropathy.

PMID- 9178147
TI  - Staphylococcus aureus in the anterior nares and subungual spaces of the hands in
      atopic dermatitis.
AB  - We examined the prevalence of Staphylococcus aureus in the anterior nares and the
      subungual spaces of the hands of patients with atopic dermatitis to determine
      whether the presence of S. aureus at these sites may contribute to the
      aggravation of the dermatitic skin lesions. The prevalence of S. aureus in the
      anterior nares of patients with atopic dermatitis was over five times higher than
      that in the anterior nares of patients with other skin diseases or in healthy
      adult controls, and the prevalence of S. aureus in the subungual spaces was 10
      times higher in patients with atopic dermatitis than in those with other skin
      diseases or in controls. Both the anterior nares and the subungual spaces of the
      hands are important reservoirs of S. aureus in atopic dermatitis. The phage type
      of S. aureus strains isolated from the anterior nares is similar to that of the
      strains isolated from the subungual spaces.

PMID- 9178148
TI  - The use of prostaglandin E2 for cervical ripening in patients requiring induction
      of labour.
AB  - A total of 290 women who required induction of labour for medical or obstetric
      reasons were given single or multiple doses of prostaglandin E2 gel (0.5 mg) to
      induce cervical ripening. Onset of labour occurred in 185 (63.8%) of the women
      treated with the gel, without any further treatment. The overall Caesarean
      section rate was 27.2% (79/290) and was significantly higher among those with an
      initially low Bishop score than in those with a higher initial score (34.7%
      versus 22.1%; P = 0.025). Prostaglandin E2 gel appears to be of considerable
      clinical benefit, especially where no other options are available except
      Caesarean section or a very long, difficult labour that may result in significant
      fetal distress.

PMID- 9178149
TI  - Efficacy of a combined diloxanide furoate-metronidazole preparation in the
      treatment of amoebiasis and giardiasis.
AB  - A combined formulation of diloxanide furoate and metronidazole was used to treat
      amoebiasis and giardiasis (cysts and vegetative forms) in 54 patients. Of these
      34 patients had amoebiasis, 19 had giardiasis and one had mixed infection. Each
      patient took one tablet (containing 500 mg diloxanide furoate and 400 mg
      metronidazole), three times daily for 5 days, and the response to therapy was
      checked by clinical examination and by examination of fresh stools on days 3, 5
      and 10. Abdominal pain was completely relieved in 91% and 84% of patients with
      amoebiasis and giardiasis, respectively, while parasitic clearance was 100% in
      both groups. Tolerance to the drug was adequate.

PMID- 9178150
TI  - Budd-Chiari syndrome: a review of ten cases.
AB  - The cases of ten patients with Budd-Chiari syndrome who were admitted to our
      medical centre between 1974 and 1986 were reviewed. There were three survivors;
      the remaining seven died after their disease had taken a rapid downhill course.
      The clinical course of Budd-Chiari syndrome and the various modalities of medical
      and surgical treatment are outlined.

PMID- 9178151
TI  - Inflammatory myopathies and systemic disorders: a review of immunopathogenetic
      mechanisms and clinical features.
AB  - The inflammatory myopathies are a heterogeneous group of muscle diseases
      characterized by muscle degeneration mediated by inflammatory processes. They may
      be idiopathic, as in polymyositis, dermatomyositis and inclusion body myositis,
      or associated with systemic disorders such as malignancies, overlap syndromes,
      and retroviral infection. The pathogenesis of each disease is discussed together
      with more recent molecular and cellular immunology findings. Salient diagnostic,
      clinical and pharmacological features are also reviewed.

PMID- 9178152
TI  - Ocular flutter and truncal ataxia may be associated with enterovirus infection.
AB  - We report on three patients who presented a rare, uniform clinical syndrome
      consisting of ocular flutter and truncal ataxia. In all patients the symptoms
      followed an upper respiratory infection and resolved without sequelae within a
      few weeks. Previous reports have emphasized the apparent relationship of this
      entity to infectious disease, but the infectious agent remained uncertain. In one
      patient we could find a significant rise in antibody titres to enterovirus. We
      are not aware of any other similar documented case.

PMID- 9178153
TI  - Differences in factors associated with silent and symptomatic MRI T2
      hyperintensity lesions.
AB  - The factors and symptomatology associated with different types of hyperintensity
      lesions on MRI were investigated. The study population consisted of 139 subjects
      who were recruited from 450 outpatients who had a neurological diagnosis in 1994.
      The subjects underwent brain magnetic resonance imaging between 1994 and 1995 and
      were divided into three groups (control, asymptomatic, and symptomatic) on the
      basis of T2 hyperintensity lesions, as well as a history of or neurological signs
      of stroke, or both. The demographic characteristics and risk factors were
      studied, and the T2 hyperintensity lesions were analysed semi-quantitatively.
      Results showed that: (1) the control and asymptomatic groups did not differ in
      terms of risk factors and demographic characteristics with the exception of age;
      (2) the symptomatic group was characterized by a significantly higher incidence
      of hypertension and electrocardiographic abnormalities, as well as significantly
      more numerous risk factors when compared with the other two groups; (3) the
      symptomatic patients also had higher proportion of men and higher levels of
      systolic blood pressure and blood glucose than the control patients, and more
      frequent hypertriglyceridaemia and higher triglyceride level than the
      asymptomatic patients; (4) the symptomatic group had a greater lesion
      distribution in the posterior basal ganglia-internal capsule and the
      infratentorial regions than did the asymptomatic group. We concluded that the
      asymptomatic and symptomatic groups should not be considered identical entities.

PMID- 9178154
TI  - Movement disorders in Japanese encephalitis.
AB  - Movement disorders in Japanese encephalitis (JE), although reported, have not
      been analyzed systematically. In this study, we report an analysis of movement
      disorders in 14 out of 17 JE patients, correlated with the radiological findings.
      All patients had at least a four fold rise of IgG antibodies against JE in a
      haemagglutination inhibition test. The patients' ages ranged between 2 and 54
      years and 4 of them were women. Extrapyramidal signs, such as hypokinesia,
      hypophonia and masking of the face, were present in all patients by the first
      month as the patients came out of the coma-except for 1 patient. Eight patients
      had axial and 3 tongue dyskinesia; rigidity was present in 6 and tremor in 2
      patients. At 3 months, these symptoms improved considerably in 6 patients.
      Cranial CT scan revealed thalamic involvement in 10, which was bilateral in 9
      patients. Two patients had brain stem and one had cerebellar involvement. Cranial
      MRI was carried out in 9 patients and revealed additional findings in lentiform
      nucleus, midbrain and pons in 3 each and cerebellum in 4 patients. Bilateral
      thalamic involvement on MRI was seen in all the patients, including two patients
      whose CT scans were normal. SPECT studies using 99mTc-ECD revealed bilateral
      thalamic hypoperfusion in all (n = 7) and frontal hypoperfusion in 3 patients. In
      JE, movement disorders are common and may be due to thalamic involvement in
      isolation or in combination with basal ganglia or midbrain or both.

PMID- 9178155
TI  - Magnetic stimulation in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common cause of dementia in which some clinical
      motor abnormalities have been described. We used transcranial magnetic
      stimulation in order to test the hypothesis that the change in the motor cortex
      might cause modifications in motor excitability. Fourteen mildly to moderately
      affected AD patients were compared with 11 controls matched for age, height and
      sex. The motor evoked potential threshold value for the relaxed abductor digiti
      minimi was lower in the AD patients than in the control group for both left and
      right hemispheres (P < 0.05). No statistically significant difference was found
      comparing the left and the right hemispheres thresholds in each population. The
      mean interside threshold differences were small and not significantly different
      between patients and controls. The spinal motor neuron excitability, as evaluated
      by F/M and H/M waves amplitude ratios, showed no difference between the groups,
      reinforcing the motor cortex increased excitability hypothesis to explain this
      difference. Degeneration of inhibitory gabaergic terminals might be the basis for
      the increased cortical excitability in the motor cortex of the Alzheimer
      patients; postsynaptic changes in the GABAA receptors might also affect
      inhibitory gabaergic transmission. The increased excitability found by
      transcranial magnetic stimulation in the motor cortex is important for
      understanding the emergence of seizures and myoclonus in this disease.

PMID- 9178156
TI  - Serial magnetisation transfer ratios in gadolinium-enhancing lesions in multiple
      sclerosis.
AB  - The magnetisation transfer (MT) ratio of eight multiple sclerosis lesions has
      been studied serially. Initially, when the lesions showed gadolinium enhancement,
      there was a marked reduction in their MT ratio compared with normal white matter.
      Follow-up a mean of 11 months later (range 3-23 months), when the lesions no
      longer enhanced, revealed a consistent and usually marked recovery of the MT
      ratios towards normal. The MT ratio is thought to reflect the structural
      integrity of tissues with an important contribution from myelin and axons. MT
      imaging is a promising tool for elucidating pathophysiology and monitoring
      treatment in multiple sclerosis.

PMID- 9178157
TI  - Source of cerebral microembolic signals in occlusion of the internal carotid
      artery.
AB  - BACKGROUND AND PURPOSE: There are several possible sources of cerebral embolic
      ischaemia distal to an occlusion of the internal carotid artery (ICA). Our aim
      was to identify the source of microembolic signals in the ipsilateral middle
      cerebral artery (MCA) by taking simultaneous bitemporal transcranial Doppler
      ultrasound recordings of the ipsilateral MCA and the contralateral ACA to find
      the route of potential microembolic material to MCA. SUBJECTS AND METHODS: The
      study group consisted of 38 patients with an occlusion of the ICA. With
      extracranial duplex sonography (ACUSON 128 XP; 7 MHz), performed by an
      experienced sonographer, the echo intensity and echo structure of the occluded
      ICA in the extracranial part (proximal) were classified as homogeneous or
      inhomogeneous. In addition, affected segments of the ipsilateral and
      contralateral carotid artery with arteriosclerotic vessel walls were compared.
      Microembolic signals were recorded with transcranial Doppler (TCD) monitoring.
      The microemboli counts in the MCA and ACA were added to the sum scores. RESULTS:
      The number of affected segments of the carotid artery on the ipsilateral (the
      bifurcation, the external or common carotid artery) and contralateral side of
      occluded ICA were equally distributed. In ipsilateral MCA 3.1, 7.1 microemboli
      (average mean, SD) with a range of between 0 and 34 were counted, in the
      contralateral ACA 0.3, 0.6 (range of between 0 and 2). Regression analysis
      confirmed the non-predictability of the microemboli variance on the ipsilateral
      side of the occlusion from the variance on the contralateral side (multiple r:
      0.024). We found no significant correlation between the echo intensity or echo
      structure of the occluded artery and an increased rate of microemboli in the
      ipsilateral MCA. CONCLUSIONS: Our results indicate a predominantly ipsilateral
      source for cerebral microemboli in ICA occlusion. The rate of cerebral
      microembolic signals was not influenced by the echo structure and echo intensity
      of the occluded ICA.

PMID- 9178158
TI  - Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of
      vascular lesions and usefulness of nerve studies in the detection of persistent
      bacilli.
AB  - Nerve biopsy specimens from 53 patients with leprosy and neuropathy were taken
      from the sural, the dorsal branch of the ulnar, or the superficial radial nerves
      and processed for light and electron microscopy. There was inflammation in 40
      cases (75%), 7 with a granulomatous reaction, various stages of fibrosis in 35
      (66%), and endoneurial vascular neoformation in 7. In two cases, small focal
      infarcts were associated with marked endoneurial inflammation compressing the
      vessels, in addition to endoneurial lymphocytic vasculitis. Most had an axonal
      neuropathy of varying degree, some with total fibre loss, others with predominant
      small myelinated and unmyelinated fibre loss. Signs of demyelination and
      remyelination were the main findings in 9 cases (17%). Bacilli were present in
      endothelial, perineurial, Schwann cells and in macrophages. On two occasions,
      they lost their alcohol acid resistance, were suspected in semithin sections, and
      confirmed ultrastructurally. The biopsy was decisive for the diagnosis of leprosy
      in 15 cases (28%), most without skin lesions. We evaluated the effectiveness of
      the treatment in 20 (37.7%), 12 without and 8 with bacilli, despite negativity in
      the skin. The diagnosis of leprosy based on skin lesions was confirmed with the
      nerve biopsy in 9 cases, 6 had an inflammatory neuropathy suggestive of leprosy
      in the absence of bacilli, and 3 had nonspecific changes in the sural nerve since
      the neuropathy was in the upper limbs. We conclude that nerve biopsy is indicated
      for the diagnosis of leprosy in cases without clinically visible skin lesions and
      to evaluate the effectiveness of the treatment. In these cases the
      ultrastructural studies are important for recognition of the bacilli. Vascular
      lesions may play an important role in the progression of the nerve damage,
      including the occurrence of focal nerve infarcts which, to our knowledge, have
      not been previously reported in association with leprosy.

PMID- 9178159
TI  - Carotid artery dissections presenting as isolated posterior cerebral artery
      infarctions.
AB  - A spontaneous dissection of the carotid artery is a well-known cause of cerebral
      infarction, mostly due to an embolus from the affected vessel segment. For
      haemodynamic and anatomical reasons the territories of the middle and anterior
      cerebral arteries are usually involved. We report two cases of carotid artery
      dissections resulting in infarctions exclusively in the territory of the
      posterior cerebral artery. The underlying anatomical conditions were a fetal
      origin of the posterior cerebral artery and an embolic supra-ophthalmic occlusion
      of the internal carotid artery. To our knowledge similar cases have not
      previously been documented.

PMID- 9178160
TI  - Peroneal nerve neuropathy in cancer patients: a paraneoplastic syndrome?
AB  - AIMS: To investigate the occurrence of symptomatic peroneal neuropathy (PN) in
      cancer patients, as well as that of cancer in PN patients and to seek possible
      factors in the aetiology of PN. METHODS: Clinical, neurographical, and
      myographical data of patients with PN, in two general neurology clinics during a
      5-year period (1988-1992) were analysed retrospectively. A population-based
      cancer registry was consulted for epidemiological data in the area. RESULTS: The
      catchment population of the two clinics consisted of 433,142 people, and 8,766
      new cancer patients were diagnosed. PN was diagnosed in 372 patients, of whom 74
      suffered from cancer (in 56 PN was believed to be related to cancer). The crude
      relative risk of PN in patients with cancer compared with patients without cancer
      was 8.6. After correction for differences in age and sex between the compared
      groups, the relative risk dropped to 3.4 (2.8 for women and 3.6 for men). The
      crude relative risk of cancer for patients with PN relative to people without PN
      was 7.5. The relative risk, after correction for age and sex, was 2.8 (2.5 for
      women and 2.9 for men). All relative risks were significant (P < 0.001), but did
      not differ between the sexes (P > 0.4). Weight loss was established in 35/56
      patients, but in 17/56 it was unknown. PN has not been found to be part of a
      polyneuropathy. Chemotherapy did not play a causal part. In some patients PN
      preceded the diagnosis of cancer. CONCLUSIONS: The occurrence of PN seems to be
      higher in patients with cancer than in people without cancer. Cancer was found in
      patients with PN more often, particularly in elderly men, than would be expected
      from the occurrence in the total population. PN in patients with cancer is
      supposed to be due to a combination of metabolic and mechanical factors. The
      findings justify a prospective study of the relation between PN and cancer.

PMID- 9178161
TI  - Paraneoplastic opsomyoclonus, cerebellar ataxia and encephalopathy associated
      with anti-Purkinje cell antibodies.

PMID- 9178163
TI  - Cerebellar syndrome due to hypoparathyroidism.

PMID- 9178162
TI  - Amantadine in advanced Parkinson's disease: good use of an old drug.

PMID- 9178164
TI  - Amyotrophic lateral sclerosis: from pathological mechanisms to patient care.

PMID- 9178166
TI  - Transgenic animal models of familial amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) occurs in both sporadic and familial forms,
      which have very similar clinical presentation and course. Approximately 20% of
      the familial cases of ALS are caused by mutation of the SODI gene encoding Cu, Zn
      superoxide dismutase (SOD). Over 30 different SODI gene mutations have been found
      in patients. Most are missense mutations that cause the substitution of one amino
      acid for another. The failure to find deletions in familial ALS suggests that the
      mutant protein is required for pathogenesis. Studies in transgenic mice indicate
      that familial ALS is caused by gain-of-function mutations in the SODI gene. These
      enhance formation of free radicals by the mutant enzyme. When expressed at high
      levels in transgenic mice, mutant human Cu,Zn SOD causes a clinical disease that
      resembles human ALS. Selective degeneration of motor neurones in the spinal cord
      and brainstem is accompanied by progressive motor impairment. Pathogenesis in the
      transgenic model of familial ALS is a sequential, two-step process in which
      damage mediated by free radicals accumulates to a threshold that triggers
      catastrophic motor neurone loss through glutamate-mediated, excitotoxic
      mechanisms. Evidence in support of this hypothesis comes from therapeutic studies
      with antioxidants and inhibitors of glutamatergic neurotransmission.

PMID- 9178167
TI  - The Riluzole Early Access Programme: descriptive analysis of 844 patients in
      France. ALS/Riluzole Study Group III.
AB  - Recent controlled trials in outpatients with amyotrophic lateral sclerosis (ALS)
      indicate that riluzole prolongs tracheostomy-free survival. After 12 months'
      treatment, riluzole 50 mg, 100 mg and 200 mg daily reduced the risk of death or
      tracheostomy (relative to placebo) by 24%, 34% and 31%, respectively (by 28%, 43%
      and 43%, respectively, after adjustment for known prognostic factors). This
      survival advantage (6-9 patients require treatment with riluzole to avoid 1
      death/tracheostomy annually) compares favourably with that achieved
      therapeutically in breast cancer and coronary artery disease. Some 6000 ALS
      patients are currently receiving riluzole 50 mg twice daily within the Riluzole
      Early Access Program. In France, this programme is being implemented as an open
      label multicentre trial to assess patients' functional status and quality of
      life. To date, 844 patients have been enrolled, and they will be followed up for
      12 months on riluzole. Baseline demographic and clinical characteristics of this
      study population are presented here.

PMID- 9178168
TI  - Health outcome and quality-of-life measurements in amyotrophic lateral sclerosis.
AB  - Quality of life has been used as a primary outcome measure in the treatment of
      cancer and cardiovascular disease, and as a secondary outcome measure in therapy
      of Parkinson's disease. However, it has been relatively neglected in studies of
      amyotrophic lateral sclerosis (ALS). Although there is need for the development
      of an ALS-specific quality-of-life measure, it will be necessary, nonetheless, to
      continue to use generic measures in order to ensure comparability of measurement
      between disease states. An argument is put forward for the use of quality-of-life
      measures as a primary end-point in future clinical trials in ALS. A distinction
      is drawn between the demonstration of biological efficacy and clinically useful
      benefit. The most likely instruments to prove useful are briefly discussed.

PMID- 9178165
TI  - Glutamate, excitotoxicity and amyotrophic lateral sclerosis.
AB  - The "glutamate hypothesis" is one of three major pathophysiological mechanisms of
      motor neurone injury towards which current research effort into amyotrophic
      lateral sclerosis (ALS) is directed. There is great structural and functional
      diversity in the glutamate receptor family which results from combinations of 14
      known gene products and their splice variants, with or without additional RNA
      editing. It is possible that motor neurones express a unique molecular profile of
      glutamate receptors. Abnormal activation of glutamate receptors is one of five
      main candidates as a final common pathway to neuronal death. In classical acute
      excitotoxicity, there is influx of Na+ and CI-, and destabilisation of
      intracellular Ca2+ homeostasis, which activates a cascade of harmful biochemical
      events. The concept of secondary excitotoxicity, where cellular injury by
      glutamate is triggered by disturbances in neuronal energy status, may be
      particularly relevant to a chronic neurodegenerative disease such as ALS. Data
      are now beginning to emerge on the fine molecular structure of the glutamate
      receptors present on human motor neurones, which have a distinct profile of AMPA
      receptors. Two important molecular features of motor neurones have been
      identified that may contribute to their vulnerability to neurodegeneration. The
      low expression of calcium binding proteins and the low expression of the GluR2
      AMPA receptor subunit by vulnerable motor neurone groups may render them unduly
      susceptible to calcium-mediated toxic events following glutamate receptor
      activation. Eight lines of evidence that indicate a disturbance of glutamatergic
      neurotransmission in ALS patients are reviewed. The links between abnormal
      activation of glutamate receptors and other potential mechanisms of neuronal
      injury, including activation of calcium-mediated second messenger systems and
      free radical mechanisms, are emphasised. Riluzole, which modulates the glutamate
      neurotransmitter system, has been shown to prolong survival in patients with ALS.
      Further research may allow the development of subunit-specific therapeutic
      targeting of glutamate receptors and modulation of "downstream" events within
      motor neurones, aimed at protecting vulnerable molecular targets in specific
      populations of ALS patients.

PMID- 9178169
TI  - Impact of riluzole on the relationship between patient and physician.
AB  - To date, there has been little systematic research on the patient-physician
      relationship in amyotrophic lateral sclerosis (ALS). Important factors in this
      relationship are the emotional state, or mood, of the patients and their
      expectations of successful therapeutic intervention. In many patients there is a
      gradual deterioration of mood with disease progression-a view supported by
      studies comparing the initial and late phases of the disease. The few studies
      examining patients' expectations of therapy revealed a strong desire to be
      informed about the disease and its course without destroying every hope. In the
      later stages of the disease patients expected compassion and help with immediate
      problems. To our knowledge there has been no systematic study on the attitude of
      physicians towards ALS patients. The lack of effective treatment and the wish to
      avoid full information about the poor prognosis are almost unique problems
      involved in dealing with ALS patients. The new option to treat with a drug that
      slows disease progression provides some alleviation for the physician. Riluzole,
      at least, partially meets this expectation. Although its efficacy is too limited
      to satisfy fully the wishes of patients and physicians, it is the first available
      drug that has been shown to slow disease progression. Thus, it may bring to an
      end the feeling that there is nothing that can be done for these patients. In our
      experience this provides relevant alleviation in the management of ALS patients.

PMID- 9178170
TI  - Oral exfoliative cytology: review of methods of assessment.
AB  - The use of oral exfoliative cytology in clinical practice declined due to the
      subjective nature of its interpretation and because there may be only a small
      number of abnormal cells identifiable in a smear. The more recent application of
      quantitative techniques, together with advances in immunocytochemistry, have
      refined the potential role of cytology, stimulating a reappraisal of its value in
      the diagnosis of oral cancer. This review considers the influence of the
      quantitative analysis of cytomorphology, DNA analysis and other tumour markers
      applied to oral exfoliative cytological samples. These studies indicate that oral
      cytology may provide an important adjunct in the assessment of the patient with a
      potentially cancerous oral lesion.

PMID- 9178171
TI  - Enhancement of calcyclin gene RNA expression in squamous cell carcinoma of the
      oral mucosa, but not in benign lesions.
AB  - Oral cancer is a neoplasm with some known causes. Proliferation genes are
      significant among its few pathogenetic and prognostic factors. Calcyclin is a
      cell-cycle-related gene, the function of which is still unclear. Its expression
      and that of Haras and histone-H3 have been investigated in an assessment of their
      pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological
      and normal mucosa of patients with squamous cell carcinoma (SCC) and benign
      lesions was reverse transcribed and amplified by the polymerase chain reaction
      (PCR). The expression of all three genes in the pathological mucosa was enhanced
      in SCC only. This suggests that they may be involved in its pathogenesis and
      provides another parameter for the differentiation of malignant and benign
      lesions.

PMID- 9178172
TI  - Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas.
AB  - P53 is overexpressed in more than 50% of all human cancers. A previous study
      suggested that p53 was also overexpressed in oral papillomas. This study was
      carried out to investigate whether p53 expression was correlated with expression
      of the cellular proliferation marker Ki-67 and the epithelial differentiation
      marker cytokeratin-4 (CK4) in oral papillomas. Formalin-fixed paraffin-embedded
      sections of 30 oral papilloma specimens and 30 unmatched normal oral mucosal
      specimens were processed for immunohistochemistry, using an avidin-biotin
      peroxidase procedure and monoclonal antibodies. A semiquantification analysis on
      p53 and Ki-67 labeling indices was performed. Twenty-eight of 30 (93%) papilloma
      specimens were positive for p53. The percentage of p53-positive cells in the
      basal layer was 60.4 +/- 14.8 (mean +/- SD, n = 28), and that of Ki-67-positive
      cells was 26.7 +/- 14.4. There was no correlation between expression of p53 and
      that of Ki-67. Expression of CK4 was inversely correlated with the expression of
      Ki-67 but not correlated with the expression of p53.

PMID- 9178173
TI  - Expression and mutations of p53 in salivary gland tumours.
AB  - A series of 219 salivary gland tumours (103 carcinomas and 116 benign tumours)
      were analysed for p53 protein expression using immunohistochemistry, and for
      mutations in p53 gene using non-radioactive single strand conformation
      polymorphism (SSCP). p53 expression was present in 36% (42/116) of the benign
      tumours and in 54% (56/103) of the carcinomas. The highest prevalence of p53
      expression was found in adenoid cystic carcinomas (69%), followed by
      mucoepidermoid carcinomas (67%). Of the benign tumours, pleomorphic adenomas
      showed the highest prevalence of p53 positivity (41%). In malignant tumours,
      expression of p53 bore no correlation to local recurrence, metastatic disease or
      survival of the patients. Exons 5 through 9 were analysed and four mutations were
      found in 20 cases of p53-immunopositive tumours and two in 20 p53-negative
      tumours. Each of the exons 5, 6 and 8/9 had two mutations, whereas no mutations
      were detected in exon 7.

PMID- 9178174
TI  - Dynamic distribution of basic fibroblast growth factor during epulis formation:
      an immunohistochemical study in an enhanced healing process of the gingiva.
AB  - Basic fibroblast growth factor (bFGF) is thought to play an important role in
      wound healing. However, its histological localization, both in normal and
      pathological conditions in the oral mucosa, has not been well documented. We have
      studied the immunolocalization of bFGF in normal gingiva and gingival epulis
      specimens corresponding to different organizing stages. In normal gingiva, bFGF
      was detected in subpopulations of macrophages, mast cells and most endothelial
      cells in the lamina propria. Granulation tissue in epulides was
      histopathologically classified into six organizing stages. In stages 1 and 2, a
      small number of bFGF-positive macrophages was seen at the periphery of ulcer
      bases. In stages 3 and 4, histologically characterized by prominent capillary
      proliferation, large numbers of bFGF-positive macrophages and mast cells were
      located within granulation tissue. A positive reaction for bFGF was also found in
      some endothelial cells and in myxoedematous stroma that was rich in heparan
      sulfate proteoglycan. In stages 5 and 6, when fibrosis was accelerated, bFGF
      positive macrophages and mast cells decreased in number and were localized only
      at the periphery of the fibrous tissue. These findings suggest that maximum
      amounts of bFGF are synthesized and released from some macrophages and mast cells
      into the extracellular matrix during neovascularization of granulation tissue.

PMID- 9178175
TI  - The in vitro adhesion of Candida albicans to buccal epithelial cells (BEC) from
      diabetic and non-diabetic individuals after in vivo and in vitro application of
      nystatin.
AB  - Buccal epithelial cells (BEC) from 12 patients with diabetes mellitus and 12 age-
      and sex-matched non-diabetic subjects were tested in vitro for adhesion of
      Candida albicans following exposure to nystatin both in vitro and in vivo.
      Adhesion was significantly reduced (P < 0.002) to cells from both the diabetic
      and non-diabetic subjects after in vitro exposure to nystatin, but the reduction
      in adhesion was variable (5.0-50.7% in control subjects and 0.5-48.4% in diabetic
      subjects) and equivalent between the two groups. In vivo exposure to nystatin
      produced no overall significant reduction in candidal adhesion to cells from
      either diabetic or control subjects.

PMID- 9178176
TI  - Oral candidiasis in HIV infection: predictive value and comparison of findings in
      injecting drug users and homosexual men.
AB  - The objectives of this study were to compare the relationship of oral candidiasis
      to HIV status, cohort and CD4+ lymphocyte values in injecting drug users and
      homosexual men and to examine its impact on prognosis. An oral examination was
      added to an ongoing longitudinal study of HIV infection. Data obtained at 6-month
      intervals included smoking, illicit drug use, medication use, symptoms and
      medical diagnoses, physical examination findings and laboratory data. In this
      study HIV+ subjects were much more likely to present with oral candidiasis than
      were HIV- subjects (OR = 6.3, P < 0.01). Injecting drug users, regardless of
      serostatus, were more likely than homosexual men to present with oral candidiasis
      (OR = 3.0, P = 0.001). In both cohorts oral candidiasis was associated with low
      CD4+ lymphocyte counts and percent ages, and Kaplan-Meier survival estimates
      showed that subjects with oral candidiasis had a poorer prognosis than those
      without candidiasis, even after controlling for CD4+ lymphocyte count.

PMID- 9178177
TI  - Autopsy findings in the tongues of 20 patients with AIDS.
AB  - An extensive examination of the tongue was performed at autopsy in 20 consecutive
      patients who had died with AIDS. Abnormalities in the tongue were detected in 18
      (90%) of the cases; the commonest lesions were ulceration (11), candidosis (8)
      and small foci of hyperkeratosis (10). The most extensive lesions were caused by
      Aspergillus infection (1), non-Hodgkin's lymphoma juxtaposed with Kaposi's
      sarcoma (1), herpetic infection (1) and candidosis (5). The disease causing death
      was identified in the tongue in two cases. There was a surprisingly low
      prevalence of oral hairy leukoplakia, which may be related to anti-viral or
      retroviral therapy.

PMID- 9178178
TI  - Synthesis and biological evaluation of new 3-aralkylamino-2-aryl-2H-1, 2,4
      pyridothiadiazine 1,1-dioxides as potential CCK-receptor ligands.
AB  - A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl
      2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to
      quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A
      and CCK-B receptor ligands. The compounds were effective as cholecystokinin
      ligands in the micromolar range of concentration, c.f. the cholecystokinin
      receptor antagonists asperlicin, lorglumide or benzotript, and were thus less
      potent than the best quinazolinones previously reported. Although the compounds
      were unsuitable for drug use, the work contributed to our understanding of the
      chemistry of unusual 2,3-disubstituted pyridothiadiazinedioxides.

PMID- 9178179
TI  - Investigation of physicochemical changes to L-asparaginase during freeze-thaw
      cycling.
AB  - L-Asparaginase derived from Erwinia chrysanthemi which is being investigated as
      an alternative to E. coli for the treatment of lymphoblastic leukaemia has been
      found in our laboratory to lose activity upon exposure to consecutive freeze-thaw
      cycles. An investigation was undertaken using several techniques to characterize
      fully the physicochemical changes L-Asparaginase is undergoing during freeze-thaw
      cycling leading to the loss of its activity. A total protein assay suggested that
      the loss of some enzyme activity was a result of protein precipitation. Circular
      dichroism (CD) studies showed a decrease of alpha-helical structure with a
      concomitant increase in beta sheet and random coil content, suggesting
      alterations in the secondary structure leading to unfolding, the first step of
      denaturation processes. The elution profiles obtained from size-exclusion
      chromatography (SEC) studies indicated the formation of several species during
      the process of freezing and thawing. Sodium dodecylsulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) studies showed bands corresponding to 1-3 kDa and 32
      kDa, suggesting that some of the species are fragments and shortened monomers
      resulting from cleavage of monomers. The molecular weight distribution obtained
      using SEC-linked light scattering indicated a substantial fraction of
      polydispersed fragments ranging from 900 Da to 3 kDa and a small fraction of
      aggregates corresponding to 300 kDa. A scheme was proposed to explain the cascade
      of events leading to the loss of soluble protein and accompanying loss of enzyme
      activity. Tetramers of the enzyme dissociate into monomers some of which are
      cleaved into small fragments. The shortened monomers then aggregate and
      precipitate.

PMID- 9178180
TI  - Effect of cationic surfactant on transport of model drugs in emulsion systems.
AB  - Excess surfactant present in emulsions can influence the rates of transport of
      incorporated drugs by micellar solubilization, alteration of the partitioning
      process and by drug-surfactant complexation. Cetyltrimethylammonium bromide
      (CTAB), a cationic surfactant was selected to investigate these phenomena as it
      forms relatively stable mineral oil-water (O-W) emulsions and has the potential
      for ionic interaction. Phenylazoaniline, benzocaine, benzoic acid and phenol were
      chosen as model drugs for this study. The emulsion critical micelle concentration
      (CMC) for CTAB determined using a combination of a membrane equilibrium technique
      and surface-tension measurement was 1.0% w/v in 10% v/v% O-W emulsion systems.
      Ionic interaction between model drugs and surfactants and drug hydrophobicity
      affected their transport rates in the emulsion systems. The transport rates of
      the lipophilic drugs (benzocaine and phenylazoaniline) and the ionized
      hydrophillic drug (benzoic acid, pH 7.0) in the emulsion systems increased with
      increasing CTAB concentration up to 0.5% w/v micellar concentration and then
      decreased at higher concentrations. The rate of transport of phenol was not
      affected by the presence of micellar phase. Ionic interaction between surfactant
      and model drugs affected transport rates of model drugs in emulsion systems. The
      micellar phase was considered to affect the overall transport rates of model
      drugs.

PMID- 9178181
TI  - Oral sustained-release cisplatin preparation for rats and mice.
AB  - A new oral sustained-release solid-dispersion preparation of cisplatin (cis
      diamminedichloroplatinum(II): cisplatin) has been developed for administration to
      small experimental animals such as mice. This preparation was obtained by
      formulating cisplatin with the water-insoluble polymer ethylcellulose and with
      stearic acid in different ratios. In-vitro dissolution studies showed that
      cisplatin release characteristics were zero-order for the formulation cisplatin
      ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start
      of the experiment. The availability of cisplatin from this preparation was
      evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was
      administered orally to rats and the resulting curve of serum cisplatin levels
      against time was compared with that obtained after intravenous infusion (20 mg kg
      1) to rats. By comparing the areas under serum concentration-time curves (AUCs),
      the bioavailability of cisplatin was estimated to be 31%. The mean residence time
      (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of
      cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum
      cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical
      studies to be the minimum effective concentration) for 24 h. The curve of serum
      cisplatin level against time suggested that cisplatin was released from the solid
      dispersion preparation in a sustained-release fashion. Similar levels were also
      maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in
      mice, which is longer than that obtained after oral administration of the
      physical mixture. The serum free-cisplatin concentration was determined to be
      0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg
      mL-1. The free fraction of cisplatin in mice serum was the same as that in human
      patient serum. Pathological examination showed that this new sustained-release
      oral cisplatin preparation did not have any side effects on the gastrointestinal
      tract. These results suggest usefulness of this new solid-dispersion preparation
      for oral cisplatin therapy in lung cancer patients.

PMID- 9178182
TI  - Encapsulation, stability and in-vitro release characteristics of liposomal
      formulations of colchicine.
AB  - The severe toxicity and low therapeutic index of colchicine limit its therapeutic
      use. Encapsulation in liposomes might reduce these toxic effects. The objective
      of this study was to determine the factors influencing encapsulation of
      colchicine in liposomes and to optimize the encapsulation parameters. Colchicine
      was encapsulated in multilamellar liposomes and large unilamellar liposomes
      prepared using various phospholipids. The effects of method of preparation, type
      of vesicle, charge, and concentration of cholesterol on encapsulation of
      colchicine in liposomes were investigated. Also, stability of colchicine under
      stress conditions and at various temperatures, and in-vitro release
      characteristics were determined. A significant difference in encapsulation of
      colchicine in multilamellar liposomes was observed when prepared by two different
      methods. Induction of charge on the liposome surface increased encapsulation of
      colchicine in multilamellar liposomes, but did not affect large unilamellar
      liposomes. The liposome preparations could withstand simulated transport
      conditions and frequent changes in temperature. Particle size and concentration
      of colchicine did not change significantly during storage at various temperatures
      for six months. In order to retain encapsulated colchicine in liposomes, storage
      at or below room temperature was found to be suitable. In-vitro release of
      colchicine from large unilamellar liposomes was biphasic and was influenced by
      two rate-limiting barriers, the dialysis membrane and the liposome bi-layers. For
      optimum encapsulation and stability of colchicine liposomes were prepared from a
      mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol and either
      stearylamine or dicetyl phosphate.

PMID- 9178184
TI  - Some effects of Cassia italica on the central nervous system in mice.
AB  - This work examines some effects of the crude ethanolic extract of the medicinal
      plant Cassia italica, given at single oral doses of 0.25, 0.5 or 1 g kg-1, on the
      central nervous system in mice. Several models of nociception have been used to
      examine the analgesic effect of the extract. HPLC fingerprinting of the extract
      was performed to ensure uniformity of the extract material used. In treated mice,
      the extract caused dose-related inhibition of acetic acid-induced abdominal
      constriction, and in the formalin test of antinociception the extract reduced
      formalin-induced pain in the second (late) but not in the first (early) phase of
      the pain. Treatment with the extract at doses of 0.5 and 1 g kg-1 significantly
      increased the reaction time in the hot-plate and warm-water tail-flick tests.
      Naloxone was ineffective in antagonizing the analgesic effect of C. italica on
      tail-flick and abdominal constriction tests, possibly indicating that the effect
      occurs via non-opiate pathways. The C. italica extract caused slight dose-related
      impairment of motor control which was significant only at a dose of 1 g kg-1.
      Treatment at the three doses used did not affect the rectal temperature of
      normothermic mice, but was effective in significantly reducing the rectal
      temperature of hyperthermic rats, 0.5 and 1 h (but not 6 h) after administration
      of the extract at doses of 0.5 and 1 g kg-1. The extract also produced
      progressive diminution in the ambulatory and total activity of treated mice for
      up to 2 h after administration. It is concluded that the crude ethanolic extract
      of C. italica has CNS depressant properties, manifested as antinociception and
      sedation.

PMID- 9178183
TI  - Experiences with the rectal use of trimethoprim.
AB  - The possibility of rectal use of trimethoprim was studied. The in-vitro
      liberation of the drug from 24 different suppository bases was examined and the
      results used to select bases for in-vivo examination. The in-vitro liberation
      from the suppositories containing 50-200 mg trimethoprim was studied by the
      method of dynamic diffusion, and the released drug content was measured
      spectrophotometrically. The in-vivo examinations were performed in anaesthetized
      rats. The concentration of trimethoprim in blood was determined by bioassay. The
      absorption of the drug in the form of oral suspension, rectal solution and
      suppository was also studied. The pharmacokinetic parameters obtained after blood
      level curve fitting were compared by use of the MedUSA 1.6 program. The best in
      vivo results were achieved with the lipohydrophilic Witepsol W 35 vehicle
      containing 10% polysorbate 20 and 10% polysorbate 61 (bioavailability = 63.8%)
      and with Witepsol W 35 containing 10% polysorbate 60 (bioavailability = 63.8%).
      The results for hydrophilic Macrogol 1540 vehicle containing 5% of Macrogol 400
      were only slightly worse (bioavailability = 52.9%). In the case of the
      lipohydrophilic Witepsol W 35 vehicle with 10% polysorbate 20 and 10% polysorbate
      61 content a significant negative exponential relationship was found between the
      administered doses and their respective bioavailability values; this tendency was
      also observed during in-vitro examinations. When incorporated in the appropriate
      vehicle trimethoprim was absorbed well. With three vehicles the extent of
      absorption exceeded that for oral administration on the same model
      (bioavailability = 38.8%). Trimethoprim rectal suppositories, which are
      formulated with the vehicles having the best in-vitro and in-vivo results, are
      suitable for clinical pharmacological investigation.

PMID- 9178185
TI  - Electrical and mechanical modulations by oxygen-derived free-radical generating
      systems in guinea-pig heart muscles.
AB  - The effects of free-radical generating systems and angiotensin-converting enzyme
      (ACE) inhibitors on the action potentials and contractile force in guinea-pig
      cardiac muscles were examined using conventional microelectrode and whole-cell
      voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM)
      prolonged 50%, 75% and 90% repolarization of action-potential duration (APD)
      approximately 15-25 min after its application. But the longer exposure reversed
      the APD shortening in a concentration-dependent manner. Other action-potential
      parameters were not altered to a significant extent. The contractile force was
      increased. Longer exposure inhibited the enhanced force (but it was still larger
      than control). The effects on the spontaneous action potential from right atrial
      muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100
      microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current.
      The effects of light-activated rose bengal (10-100 nM) on the APD were similar
      to, but more potent than, those of H2O2. The response was observed rapidly after
      a light illumination. During exposure to rose bengal (100 nM), abnormal
      spontaneous action potentials or arrhythmias such as a bigeminy occurred,
      presumably because of early and delayed afterdepolarizations. The responses were
      irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected
      the changes induced by these free radicals. These results indicate that H2O2 has
      a dual, time-dependent, action on the APD and rose bengal with light illumination
      produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i
      and then cellular Ca2+ overload occurred. These responses were protected by ACE
      inhibitors.

PMID- 9178186
TI  - A structure-relationship study of the uptake of aliphatic polyamine compounds by
      rat intestinal brush-border membrane vesicles.
AB  - The effects of lipophilicity, ion-diffusion potential and membrane surface
      potential on the uptake of various aliphatic polyamine compounds by rat
      intestinal brush-border membrane vesicles (BBMV) have been investigated. A
      valinomycin-induced potassium-diffusion potential (inside-negative) stimulated
      the initial uptake of diamine compounds, and good correlation was observed
      between lipophilicity and the amount of diffusion-potential-dependent transport
      of the diamines. In contrast, because of their much lower lipophilicity, tri- and
      tetraamine compounds were not affected by the diffusion potential. Tetracaine,
      which can make the membrane surface potential more positive, inhibited the
      transport rate of 1,9-nonanediamine, spermidine and spermine by the BBMV. These
      data suggest that the transport mechanism of diamines is similar to that of
      monoamine compounds in respect to its dependence on ion-diffusion potential and
      on the membrane surface potential. The extent of the effect of ion-diffusion
      potential on the rate of transport of the diamines was closely related to the
      lipophilicity of the diamine. In contrast, only the surface potential contributed
      to the transport mechanism of lower lipophilic tri- and tetraamine compounds.

PMID- 9178187
TI  - Characteristics of cefdinir uptake by rabbit small intestinal brush-border
      membrane vesicles.
AB  - Aminocephalosporins with peptide-like structures have been shown to be absorbed
      by the intestinal peptide carrier. We investigated the transport mechanism of
      cefdinir, an oral monocarboxylic acid cephalosporin, using rabbit small
      intestinal brush-border membrane vesicles. Transport of cefdinir showed a slow
      and almost linear uptake rate for concentrations up to 30 mM with and without and
      inward H+ gradient. No overshoot phenomenon was observed in the presence of an
      inward H+ gradient. The uptake rate increased only slightly with decreasing
      extravesicular pH, and a protonophore had little effect on the uptake.
      Aminocephalosporins such as cephalexin only slightly inhibited cefdinir uptake
      even in the presence of an inward H+ gradient, and vice-versa. Monocarboxylic
      acids such as acetic acid and salicylic acid had little effect on cefdinir
      uptake. These findings suggest that in contrast with other oral cephalosporins
      cefdinir uptake through the brush-border membrane is slow and involves a
      mechanism similar to passive diffusion.

PMID- 9178188
TI  - Effects of ATP on phosphoinositide hydrolysis and prostaglandin E2 generation in
      rabbit astrocytes.
AB  - Extracellular ATP secreted from stimulated nerves plays a role in
      neurotransmission. This study examined the effects of extracellular ATP on
      phospholipase A2 and C signalling pathways in rabbit astrocytes. ATP caused
      prostaglandin E2 (PGE2) generation and phosphoinositide hydrolysis in a time- and
      concentration-dependent manner. A P2y purinoceptor-selective agonist, 2
      methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE2 generation.
      A P2x purinoceptor-selective agonist, alpha, beta-methylene-ATP did not cause
      either phosphoinositide hydrolysis or PGE2 generation. Although pertussis toxin
      had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it
      markedly decreased ATP-induced PGE2 generation, with significant inhibition of
      phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently
      inhibited ATP-induced PGE2 generation, caused partial inhibition of
      phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component
      of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase
      metabolites of arachidonic acid. These results suggest that a stimulation of P2y
      receptor results in phospholipase C activation in a pertussis toxin-insensitive
      manner, and that a P2 receptor other than the P2y or P2x subtypes is involved in
      ATP-induced phospholipase A2 activation via a pertussis toxin-sensitive G
      protein.

PMID- 9178189
TI  - Inhibitory effects of N-acetylcysteine on superoxide anion generation in human
      polymorphonuclear leukocytes.
AB  - It has been suggested that reactive oxygen species released by activated
      polymorphonuclear leukocytes (PMN) in man is one mechanism of tissue injury.
      Therapeutic action aimed at increasing antioxidant defence mechanisms is still a
      clinical challenge. This study examines the activity of N-acetylcysteine, a known
      antioxidant, in the protection of PMN exposed in-vitro to the chemoattractant
      peptide fMet-Leu-Phe (FMLP), the protein kinase C activator phorbol myristate
      acetate or the lipid peroxidation promoter t-butyl hydroperoxide. FMLP (3-300 nM)
      and phorbol myristate acetate (160 pm-160 nM) induced concentration-related
      superoxide anion generation. Pre-treatment with N-acetylcysteine (33-333 microM)
      resulted in concentration-related inhibition of superoxide production induced by
      FMLP (30 nM) or phorbol myristate acetate (16 nM);-log IC50 values were 3.97 +/-
      0.07 and 3.91 +/- 0.10, respectively. Changes in intracellular calcium ion
      concentration ([Ca2+]i) induced by FMLP (30 nM) were studied in fura-2-loaded
      human PMN. FMLP produced a transient calcium response, i.e. a peak followed by
      decay to a residual value above baseline. N-Acetylcysteine (333 microM) did not
      affect either basal [Ca2+]i values or changes in [Ca2+]i values after treatment
      with FMLP. Activation by phorbol myristate acetate caused a reduction in
      glutathione levels from 5.94 +/- 0.86 (control) to 1.84 +/- 0.51 nmol/3 x 10(6)
      cells (P < 0.05 compared with control). Pre-treatment with N-acetylcysteine (333
      microM) fully reversed the reduction in glutathione levels induced by phorbol
      myristate acetate (4.83 +/- 0.68 nmol/3 x 10(6) cells; P > 0.05 compared with
      control). Exposure to t-butyl hydroperoxide (0.5 mM, 30 min) markedly increased
      malondialdehyde levels (from 0.03 +/- 0.02 to 0.73 +/- 0.07 nmol/10(6) cells),
      and index of lipid peroxidation. Malondialdehyde levels were significantly
      reduced in PMN treated with N-acetylcysteine (333 microM; 0.55 +/- 0.04
      nmol/10(6) cells; P < 0.05 compared with untreated cells exposed to t-butyl
      hydroperoxide). In conclusion, N-acetylcysteine reduces superoxide generation in
      response to FMLP and phorbol myristate acetate and partially protects against
      lipid peroxidation in PMN from man. The protection afforded by N-acetylcysteine
      is not related to alteration of the intracellular calcium signal but might be
      effected by replenishment of the intracellular glutathione levels.

PMID- 9178190
TI  - 2',5'-Dihydroxychalcone as a potent chemical mediator and cyclooxygenase
      inhibitor.
AB  - Eleven chalcone derivatives have been tested for their inhibitory effects on
      platelet aggregation in rabbit platelet suspension and the activation of mast
      cells and neutrophils. Arachidonic acid-induced platelet aggregation was potently
      inhibited by almost all the compounds and some also had a potent inhibitory
      effect on collagen-induced platelet aggregation and cyclooxygenase. Some
      hydroxychalcone derivatives showed strong inhibitory effects on the release of
      beta-glucuronidase and lysozyme, and on superoxide formation by rat neutrophils
      stimulated with the peptide fMet-Leu-Phe (fMLP). We found that the anti
      inflammatory effect of 2',5'-dihydroxychalcone was greater than that of
      trifluoperazine. 2'5'-Dihydroxy and 2',3,4,5'-tetrahydroxyl chalcones, even at
      low concentration (50 microM), tested in platelet-rich plasma from man almost
      completely inhibited secondary aggregation induced by adrenaline. These results
      suggest that the anti-platelet effects of the chalcones are mainly a result of
      inhibition of thromboxane formation.

PMID- 9178191
TI  - Effect of a chymotrypsin-like inhibitor, TPCK, on histamine release from cultured
      human mast cells.
AB  - The involvement of endogenous proteases in the secretory process from human mast
      cells remains to be clarified. A chymotrypsin-like protease inhibitor, N-tosyl-L
      phenylalanylchloromethyl ketone (TPCK), blocked both FceRI- and A23187-mediated
      histamine release from cultured human mast cells at concentrations above 1
      microM. At 10 microM, the concentration that completely inhibited FceRI-mediated
      histamine release, TPCK did not inhibit the chymase activity of the lysate or
      that in intact cells. The addition of TPCK to cells 30 min before challenge did
      not affect FceRI- or A23187-mediated Ca2+ mobilization. These findings suggest
      that a TPCK-sensitive molecule distinct from chymase is involved in a late stage
      of the process of histamine release from mast cells in man.

PMID- 9178192
TI  - Some histamine-related compounds interacting with the benzylamine-oxidizing
      activity of rat white adipocytes.
AB  - In rat white adipocytes histamine is oxidized by a semicarbazide-sensitive amine
      oxidase which has benzylamine or preferential substrate (Bz-SSAO). To determine
      whether Bz-SSAO could control the extracellular levels of histamine and other
      histamine-related compounds active in lipid mobilization, a series of
      histaminergic compounds was screened as possible substrates or inhibitors of Bz
      SSAO activity. Histaminergic compounds with imidazolo or thiazolo groups are
      oxidized by rat white-adipocyte Bz-SSAO whereas S-isothiourea derivatives, with
      two- or three-carbon-atom alkyl chains between the isothiourea and the N,N
      dimethyl residue are, instead, inhibitors of the enzyme. Amtamine has been
      identified as a selective, high affinity substrate for rat white adipocyte Bz
      SSAO. This enzymatic degradation might represent a catabolic pathway for the
      drug. These results show that the histaminase property of the rat white-adipocyte
      enzyme Bz-SSAO also extends to other histamine derivatives active at histamine
      receptors.

PMID- 9178193
TI  - Contribution of cytochrome P450 3A pathway to bromocriptine metabolism and
      effects of ferrous iron and hypoxia-re-oxygenation on its elimination in the
      perfused rat liver.
AB  - The contribution of the cytochrome P450 3A pathway to bromocriptine metabolism,
      and the effects of ferrous iron and hypoxia-re-oxygenation on its elimination,
      were evaluated with the perfused rat liver. Outflow profiles of bromocriptine
      after bolus administration were estimated by moment analysis and dispersion model
      analysis. Kinetic parameters were not significantly changed by troleandomycin, a
      P450 3A inhibitor. The inhibition of bromocriptine metabolism by troleandomycin
      was 5.7 +/- 2.4%. These findings indicate that cytochrome P450 3A does not play
      an important role in bromocriptine elimination with the perfused rat liver.
      Elimination rate constant (ka) values were significantly increased by ferrous
      iron perfusion or hypoxia-re-oxygenation. Free-radical generation can, therefore,
      affect bromocriptine elimination. Our observations suggest that bromocriptine
      might be eliminated by scavenging of free radicals in the liver.

PMID- 9178194
TI  - Pharmacological activity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.):
      assessment by inhibition of human polymorphonuclear leukocyte chemiluminescence
      in-vitro.
AB  - The bioactivity of feverfew (Tanacetum parthenium) leaf extracts has been
      analysed, by use of a human polymorphonuclear leukocyte (PMNL) bioassay, to
      assess the relative contributions of solvent extraction and parthenolide content
      to the biological potency of the extract. Extracts prepared in acetone-ethanol
      (system 1) contained significantly more parthenolide (mean +/- s.d. 1.3 +/- 0.2%
      dry leaf weight) than extracts in chloroform-PBS (phosphate-buffered saline;
      system 2; 0.1 +/- 0.04% dry leaf weight) or PBS alone (system 3; 0.5 +/- 0.1% dry
      leaf weight). Extract bioactivity, measured as inhibition of phorbol 12-myristate
      13-acetate-induced, 5-amino-2,3-dihydro-1,4-phthalazinedione (luminol)-enhanced
      PMNL, chemiluminescence, followed a similar trend. Extracts inhibited phorbol 12
      myristate 13-acetate-induced oxidative burst by amounts which, if solely
      attributable to parthenolide, indicated parthenolide concentrations for the
      respective solvent systems of 2.2 +/- 0.6%, 0.2 +/- 0.1% and 0.9 +/- 0.1% dry
      leaf weight. The mean ratio of parthenolide concentration to the parthenolide
      equivalent/PMNL-bioactivity value, for acetone-ethanol and PBS extracts were both
      1:1.7. Parthenolide, although a key determinant of biological activity for T.
      parthenium leaf extracts based on the PMNL-bioassay, seems not to be the sole
      pharmacologically-active constituent. The identical and elevated bioactivity
      parthenolide ratios for both organic and aqueons-phase leaf extracts suggest that
      a proportion of the other bioactive compounds have solubilities similar to that
      of parthenolide.

PMID- 9178195
TI  - A sulphonoglycolipid from the fern Polypodium decumanum and its effect on the
      platelet activating-factor receptor in human neutrophils.
AB  - The South American fern Polypodium decumanum, traditional name calaguala, has
      documented clinical use in oral treatment of skin disorders, including psoriasis.
      The inflammatory mediator platelet-activating factor (PAF), has been implicated
      in the pathogenesis of psoriasis. A constituent of a calaguala extract has been
      shown to have inhibitory activity in a PAF-induced exocytosis model in human
      neutrophils. The compound was identified as the sulphoquinovosyl diacylglycerol
      1,2-di-O-palmitoyl-3-O-(6-sulpho-alpha-D-quinovopyranosyl)-glycero l by
      spectroscopic means. When subsequently studied in an in-vitro model for [3H]PAF
      binding in neutrophils from man the compound caused dose-dependent displacement
      of [3H]PAF from its receptor with an IC50 value of 2 microM. It is suggested that
      the compound acts through PAF receptor antagonism in intact human neutrophils.

PMID- 9178196
TI  - Mechanisms involved in the antinociceptive effect in mice of the hydroalcoholic
      extract of Siphocampylus verticillatus.
AB  - The antinociception caused by the hydroalcoholic extract of Siphocampylus
      verticillatus (Campanulaceae) has been investigated in chemical and thermal
      models of nociception in mice. We have also assessed some of the mechanisms
      underlying the antinociceptive effect of the extract. The hydroalcoholic extract
      of S. verticillatus (60-1000 mg kg-1, i.p. or p.o.) produced dose-related,
      significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced
      abdominal constriction in mice, with ID50 values of 204 and approximately 1000 mg
      kg-1, respectively. In the formalin test, the extract (100-1000 mg kg-1), given
      either intraperitoneally or orally, resulted in graded inhibition of both phases
      of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the
      second phase of the pain. The calculated mean ID50 (mg kg-1) values for the
      earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In
      addition, the extract (60-1000 mg kg-1, i.p. or p.o.) caused marked and dose
      related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of
      420 and 485 mg kg-1, respectively. The hydroalcoholic extract, at the same doses,
      did not significantly affect the performance of animals in the rota-rod test, nor
      did it have any analgesic effect in the tail-flick or hot-plate tests. The
      treatment of animals with naloxone (5 mg kg-1, s.c.) significantly reversed the
      analgesic effect of both morphine (5 mg kg-1, s.c.) and the extract (300 mg kg-1,
      i.p.) when assessed against acetic acid-induced abdominal constrictions. The
      treatment of animals with L-arginine (600 mg kg-1, i.p.) significantly attenuated
      the antinociceptive effects of NG-nitro-L-arginine (L-NOARG) (75 mg kg-1, i.p.),
      of the hydroalcoholic extract (600 mg kg-1, i.p.) or of morphine (5 mg kg-1,
      s.c.), when analysed against the formalin test. In addition, adrenalectomy of
      animals 7 days before the tests significantly reversed the antinociception caused
      by the hydroalcoholic extract (300 mg kg-1, i.p.) in the formalin-induced pain.
      These data show that the hydroalcoholic extract of S. verticillatus has
      significant and long-lasting oral antinociception when assessed against both
      neurogenic and inflammatory models of nociception in mice. The precise mechanism
      responsible for the analgesic effect of the extract still remains unclear, but a
      great part of this effect seems to be partly related to an opioid-like action and
      involvement of the L-arginine-nitric oxide pathway. Finally, the antinociception
      caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal
      hormones.

PMID- 9178198
TI  - Asthma: a cause for public and governmental concern?

PMID- 9178197
TI  - Analysis of rabbit vascular responses to DBI, an ingol derivative isolated from
      Euphorbia canariensis.
AB  - We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI),
      an ingol derivative isolated from E. canariensis, on isometric tension developed
      by isolated rabbit basilar and carotid arteries. Concentration-response curves to
      DBI (10(-8) - 3 x 10(-5) M) were obtained cumulatively in both arteries at
      resting tension and active tone (KCI, 50 mM). At resting tension, DBI induced a
      concentration-dependent contraction, which was not inhibited in Ca(2+)-free
      medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10(-4)
      M) inhibited the DBI-induced contraction both in basilar and in carotid arteries.
      Calmidazolium (10(-4) M) inhibited the maximum contraction of the carotid artery
      to DBI, and completely abolished the response in the basilar artery. In pre
      contracted basilar arteries DBI induced a concentration-dependent relaxation that
      was not modified by incubation with NG-nitro-L-arginine (L-NOARG; 10(-5) M) or
      indomethacin (10(-5) M). In the carotid artery with active tone DBI induced
      further contractions, which were not significantly modified by L-NOARG (10(-5) M)
      and were potentiated by indomethacin (10(-5) M). These results suggest that DBI
      contracts rabbit basilar and carotid arteries by a mechanism that is independent
      of extracellular Ca2+ and involves the participation both of protein kinase C and
      of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism
      independent of the liberation of nitric oxide and prostacyclin. In the carotid
      artery prostacyclin but not nitric oxide partially counteracts the contractile
      action of DBI.

PMID- 9178199
TI  - Asthma: confidence in definition and diagnosis?

PMID- 9178200
TI  - Bronchial hyperresponsiveness: what causes twitchy airways?

PMID- 9178201
TI  - Current therapy for asthma: time for a change?

PMID- 9178202
TI  - Current drug treatment of asthma.

PMID- 9178203
TI  - Phosphodiesterase inhibitors: knockout drops?

PMID- 9178204
TI  - Novel approaches to the inhibition of cytokine responses in asthma.

PMID- 9178205
TI  - Adhesion molecules and asthma.

PMID- 9178206
TI  - Epidemiologic evidence of an association between air quality and asthma.

PMID- 9178207
TI  - Management of asthma in childhood.

PMID- 9178208
TI  - Community care of asthma: the pharmacist as counsellor?

PMID- 9178209
TI  - Assessing equivalence of inhaled products.

PMID- 9178210
TI  - The quality management jigsaw.
AB  - The current scene in Australia, as in a large part of the developed world, in
      relation to the subject of quality management in health care, is characterized by
      confusion, blurred objectives, patchy involvement and very high opportunity
      costs. Much of the confusion is caused by a failure to understand or use
      correctly the bewildering array of terminology that characterizes what is
      becoming a new discipline in its own right. A series of simple definitions
      permits the reader to understand what the author is attempting to say. The paper
      also provides a conceptual framework for the implementation of quality management
      in hospitals: a jigsaw of activity which hospitals have some difficulty
      conceptualizing and without which hospitals will never be able to respond
      seriously to the challenge of assuring quality.

PMID- 9178211
TI  - The impact of screening for risk factors associated with postnatal depression at
      the first prenatal visit.
AB  - Although 10-15% of Australian women suffer from postnatal depression (PND), few
      efforts have been made, prenatally, to predict which women may develop the
      condition. The objective of this study was to evaluate the impact on patients,
      staff and services of an intervention designed to identify women at risk for PND.
      Women were screened at their first prenatal visit for factors associated with
      PND, and were asked to complete a questionnaire at their next clinic visit to
      assess the impact of the screening questions and the usefulness of a PND
      information kit. To assess the impact of the intervention on the prenatal clinic
      routine, all staff associated with the intervention were interviewed individually
      and their responses were tape recorded and analysed for themes. Patients reported
      a high level of satisfaction with the intervention. Staff responded well to the
      new procedure and offered constructive comments to improve the process.

PMID- 9178212
TI  - Nosocomial infection indicators in Australian hospitals: assessment according to
      hospital characteristics.
AB  - The relationship of bed size and hospital type (private or public) was studied
      using Hospital-Wide Medical Indicator data on nosocomial infections submitted to
      the Australian Council on Healthcare Standards Care Evaluation Program by
      hospitals presenting voluntarily for accreditation in 1993. The aim was to
      determine if this process could simplify the establishment of hospital peer
      groups for comparison of risk in the absence of knowledge of patient illness
      severity indices. After adjusting for potential confounders in a logistic model,
      hospital type was found to be a significant predictor for the occurrence of
      infection in clean and contaminated wounds. Bed size was a significant predictor
      for the occurrence of hospital-acquired bacteraemia in private and public
      hospitals. The increase in the risk of developing hospital acquired bacteraemia
      with increasing number of beds was significant as a trend (P < 0.0001) in private
      as well as public hospitals. The results suggest that hospital type and bed size
      are initial indices for 'flagging' peer group variation and prompting a more
      detailed internal review.

PMID- 9178213
TI  - Changes in psychotropic medication use in nursing homes over a 9-month period.
AB  - A 1993 survey of nursing home residents in one part of Sydney was repeated 9
      months later. Details of psychotropic medication given to the 1433 residents who
      survived and remained in the same 38 nursing homes were examined. There were
      modest reductions in the percentage of residents taking neuroleptics, anxiolytics
      and hypnotics, but there was an increase from 16.0% to 17.6% in the percentage of
      residents taking antidepressants. About 65% of those taking psychotropic
      medication at the initial survey remained on exactly the same dose 9 months
      later. Most of those taking neuroleptic or antidepressant medication were given
      relatively small daily doses. Intervention studies are desirable to examine how
      best to improve prescribing practices.

PMID- 9178214
TI  - Comprehensive audit of quality-of-care and quality-of-life for patients with
      diabetes.
AB  - This comprehensive audit was conducted in a three-person general practice with an
      age-sex-disease register to evaluate care for patients with diabetes using
      metabolic indicators and validated measures of quality-of-life and patient
      satisfaction. Medical records were reviewed using criteria derived from
      guidelines published by Diabetes Australia and New South Wales Health. Self
      administered questionnaires mailed to patients included the Diabetes Quality-of
      Life measure (DQOL), the Well-Being Questionnaire (WBQ) and the Diabetes
      Treatment Satisfaction Questionnaire (DTSQ). Record audit for 71 patients with
      diabetes demonstrated poor control and monitoring. Frequent attenders were no
      more likely to have had a HgA1c performed than less frequent attenders (P =
      0.72). While patient satisfaction with care was high, numerical values for
      quality-of-life were lower than published overseas norms, indicating a need to
      support better care in general practice and further research to determine
      Australian norms.

PMID- 9178215
TI  - Pregnancy outcome score: a clinical indicator of the childbirth process.
AB  - Clinical indicators associated with the process of childbirth are either gross
      (e.g. perinatal mortality rate) or measures of intervention (e.g. Caesarean
      section rate). Morbidity and process are rarely, if ever, addressed. We developed
      and piloted a simple pregnancy outcome score as a comparative indicator of
      outcome. This scoring system is easy to apply, and there was a positive and
      significant correlation between the pregnancy outcome score and the risk status
      of the patients.

PMID- 9178216
TI  - Orthopaedic surgery outcomes assessment model.
AB  - This paper reviews the motives and methods for applying an outcomes assessment
      model in the orthopaedic department at our hospital. Various strategic
      applications of health status measurement are demonstrated. The methods used in
      the process of designing this model are highlighted which may assist design of
      outcomes assessment models in other fields. A variety of surgical interventions
      were incorporated into this model including lower limb arthroplasties, total
      shoulder arthroplasty and all shoulder soft tissue surgery.

PMID- 9178217
TI  - Difference in quick phases induced by horizontal and vertical vestibular
      stimulations: role of the otolithic input.
AB  - Quick phases (QPs) induced by horizontal and vertical sinusoidal vestibular
      stimulations were studied in rabbits, cats, and humans. In all the animals, large
      and frequent horizontal QPs were observed following yaw stimulation in prone
      position. By contrast, QPs were almost absent during roll stimulation in rabbits,
      and they were small and oblique during pitch stimulation in cats and humans. As a
      result of these differences, the range of gaze displacement induced by vestibular
      stimulations was greater in the horizontal plane than in the vertical one. We
      also found that the trajectory of the QPs in rabbits was kept horizontal even
      when the yaw rotation was off vertical axis of +/- 45 degrees in the sagittal
      plane. Moreover, in the rabbit, the rare horizontal QPs induced by roll
      stimulation did not change their orientation at various pitch angles of roll
      stimulation axis. The QPs were also analyzed following roll stimulation of the
      rabbit in supine position. In this condition, in which the otolithic receptors
      were activated in the opposite way compared to prone position, large vertical QPs
      were elicited. We concluded that these results provide evidence that the
      otolithic signal plays a role in controlling occurrence and trajectory
      orientation of the QPs.

PMID- 9178218
TI  - Kinematic analysis of locomotion in unilateral vestibular neurectomized cats.
AB  - The vestibular syndrome following unilateral lesion of the vestibular system and
      the subsequent behavioral compensation over time have been well documented in
      many species. However, the locomotor pattern changes and the behavioral
      strategies used to preserve balance have still not been described. This study was
      aimed at quantitatively describing posturolocomotor behavior in cats tested
      before and after unilateral vestibular neurectomy (UVN) by the rotating beam
      test, which provides locomotor tasks of various difficulty. The position of head,
      neck, and trunk and the trajectory of the forelimbs and hindlimbs were recorded
      in 5 cats by 3D motion analysis. Step length and frequency walking velocity, and
      body height were computed. Results showed that normal cats adapted their
      locomotor patterns to the speed of beam rotation by increasing step length and/or
      frequency, that is, by increasing walking velocity, but without drastically
      changing their body posture. By contrast, UVN cats typically lowered their body
      centers of gravity and modified their locomotor patterns according to the
      locomotor task. Mean walking velocity was decreased in the low range of beam
      rotation as a result of smaller step length and lower frequency, and it was
      increased in the high range by opposite effects on these step cycle parameters.
      Modifications of the locomotor parameters were a function of the direction of
      beam rotation, showing significant reduction of step length, frequency, and
      velocity in the low range of counterclockwise compared to clockwise beam
      rotation, that is, during rotations toward the lesioned side. Phase plane plots
      of foot linear velocity with respect to foot linear displacement along the
      horizontal longitudinal axis displayed two different limit cycles, adapted to
      easy (low range of beam rotation) and more difficult (high range of rotation)
      walking conditions, in the normal cat. These dynamic profiles of the trajectories
      of the limbs during the step cycle were not greatly modified after vestibular
      lesion, but the phase plane typically observed in the high range for the normals
      was also found in the low range for the UVN cats. Thus, locomotor equilibrium
      function in the cat is strongly impaired following UVN, but locomotor balance can
      still be achieved in the UVN cats by the development of adaptive posturolocomotor
      strategies compensating for the lack of vestibular inputs.

PMID- 9178219
TI  - Visual object localization through vestibular and neck inputs. 1: Localization
      with respect to space and relative to the head and trunk mid-sagittal planes.
AB  - Object localization in space signals in the absence of an external reference
      (visual, auditory, haptic) involves a signal of the head in space (vestibular).
      The present study asks whether signals of body position relative to the support
      surface (proprioceptive) are involved as well, by investigating the role of
      vestibular-neck interaction (dissociating head and trunk position). Normal human
      subjects saw a light spot (object) and continuously nulled displacement steps of
      the spot. They did so before and after vestibular and/or neck rotational
      stimulation in the horizontal plane, reproducing a predesignated object
      localization in space (i), relative to the head mid-sagittal (ii), and relative
      to the trunk mid-sagittal (iii). The predominant frequency contained in the
      stimuli was varied (0.05, 0.1, and 0.4 Hz). (I) Object localization in space upon
      whole-body rotation (vestibular stimulus) at high frequency was veridical,
      whereas that at low frequency fell short. Almost identical results were obtained
      for trunk rotation about the stationary head (neck stimulus). In contrast, when
      combining the stimuli in the form of head rotation on the stationary trunk, the
      results were veridical, independent of stimulus frequency. Additional findings
      obtained with a large variety of vestibular-neck stimulus combinations suggest a
      linear summation of vestibular and neck signals. (II) Object localization with
      respect to the head was approximately veridical, being independent of vestibular
      and neck stimulation. However, this only applied if subjects were not biased by a
      head-in-space motion illusion of neck origin. (III) Object localization with
      respect to the trunk was veridical in all conditions tested. The findings support
      a recently developed concept, according to which humans evaluate the kinematic
      state of a visual object in space by (a) relating it to that of the body support
      by means of an essentially ideal proprioceptive coordinate transformation, and
      (b) relating, in turn, the kinematic state of the support to a vestibularly
      derived notion of space, using a proprioceptive coordinate transformation that
      "knows" the vestibular transfer characteristics. One important aspect is that
      object localization in space always is veridical during head and trunk rotation
      relative to a stationary support (for example, the ground) despite non-ideal
      vestibular transfer characteristics. Additional findings in patients with chronic
      loss of vestibular function confirm this concept.

PMID- 9178220
TI  - Visual object localization through vestibular and neck inputs. 2: Updating off
      mid-sagittal-plane target positions.
AB  - The vestibular signal plays a significant role in sensing changes in head
      orientation during rotations and in determining the magnitude of the rotations,
      but has only minor contributions in updating the internal representation of
      object positions with respect to the body after body rotations. The small
      contribution of the vestibular signal in egocentric object localization was
      evidenced in experiments in which the subjects reported the remembered position
      of eccentric earth-fixed targets after passive body rotations. The experiment
      reported here tested whether motor systems, such as the oculomotor system, make
      use of vestibular signals to generate accurate goal-directed motor responses
      toward a target whose position needs to be updated with respect to the body
      during and after whole-body rotations. The results showed that although subjects
      can produce saccadic eye movements of about the same magnitude as passive whole
      body rotations (as previously reported by a number of researchers), they failed
      to generate accurate saccades toward the position of an extinguished peripheral
      visual target after the rotation. Overall, these results combined with those
      found in the literature suggest different central processes for determining
      changes in body orientation in complete darkness and for updating a target
      position with respect to the body during and after body rotations.

PMID- 9178221
TI  - Head-trunk coordination during hops using one or two feet in children and adults.
AB  - The main purpose of this study was to investigate the development of head-trunk
      coordination during single hops using one foot or two feet in children of two
      ages (5.5 to 6 and 7 to 7.5) and adults (n = 6/group). The kinematics of the
      subjects' hops were analyzed by means of an automatic optical TV-image processor
      called the ELITE system. The absolute angular dispersion of the head, trunk, and
      leg about the pitch and the roll axis were measured. Head and trunk pitch and
      roll anchoring indexes were calculated in order to compare the stabilization of a
      given segment with respect both to external space and to the underlying
      anatomical segment. Results were analyzed separately for 3 phases: take-off,
      flight, and landing. Only the last two phases, flight and landing, are presented
      in this paper, and the following was found: 1) During flight, under both unipedal
      and bipedal conditions, head and trunk stabilization in space about the pitch
      axis occurred in children as well as in adults, suggesting an articulated
      operation of the head-trunk unit. In contrast, during landing, in children and
      adults, head stabilization in space tended to disappear while trunk stabilization
      in space was still present, suggesting an en bloc operation of the head-trunk
      unit. Similarly, pelvis stabilization in space about the roll axis occurred in
      all subjects during both flight and landing under unipedal conditions, where
      lateral balance control is of primary importance. Taken together, these results
      suggest that head stabilization in space is phase dependent, while trunk
      stabilization is phase independent. The trunk, including the pelvis, may thus
      constitute a stable reference frame from which anteroposterior and lateral
      balance control is organized during hops. 2) For head-trunk coordination,
      whatever the component of rotation, the two groups of children differed from
      adults, but did not differ from each other, suggesting that, while jumping, the
      transition between 6 and 7 years of age in the organization of balance control
      takes place in the coordination of the lower limbs during the preparatory phase
      of the take-off.

PMID- 9178222
TI  - Locomotor head-trunk coordination strategies following space flight.
AB  - During locomotion, angular head movements act in a compensatory fashion to oppose
      the vertical trunk translation that occurs during each step in the gait cycle.
      This coordinated strategy between head and trunk motion serves to aid gaze
      stabilization and perhaps simplifies the sensory coordinate transformation
      between the head and trunk, allowing efficient descending motor control during
      locomotion. Following space flight, astronauts often experience oscillopsia
      during locomotion in addition to postural and gait instabilities, suggesting a
      possible breakdown in head-trunk coordination. The goal of the present
      investigation was to determine if exposure to the microgravity environment of
      space flight induces alteration in head-trunk coordination during locomotion.
      Astronaut subjects were asked to walk (6.4 km/h, 20 s trials) on a motorized
      treadmill while visually fixating on a centrally located earthfixed target
      positioned either 2 m (FAR) or 30 cm (NEAR) from the eyes. In addition, some
      trials were also performed during periodic visual occlusion. Head and trunk
      kinematics during locomotion were determined with the aid of a video-based motion
      analyzing system. We report data collected preflight (10 days prior to launch)
      and postflight (2 to 4 hours after landing). The coherence between pitch head and
      vertical trunk movements during gaze fixation of both FAR and NEAR targets was
      significantly reduced following space flight indicating decreased coordination
      between the head and trunk during postflight locomotion. Astronauts flying on
      their first mission showed greater alterations in the frequency spectra of pitch
      head movements as compared to their more experienced counterparts. These
      modifications in the efficacy of head movement control may account for the
      reported disruption in gaze performance during locomotion and may contribute to
      postflight postural and gait dysfunction.

PMID- 9178223
TI  - The significance of motion sickness in the vestibular system.
AB  - In order to clarify the significance of motion sickness in the vestibular system,
      we compared the findings of experimental motion sickness between different kinds
      of subjects, some of which were already reported. Subjects were healthy adults,
      healthy children between the ages of 4 and 15 years, and patients with congenital
      and acquired labyrinthine loss. They were asked to walk while wearing
      horizontally and vertically reversing goggles. Equilibrium ataxia as well as
      motion sickness were evoked by horizontal reversal, but not by vertical reversal
      in healthy subjects. Kindergarten children exhibited severe ataxia, but little
      nausea. The frequency of severe ataxia decreased during growth, inversely as the
      frequency of nausea syndrome increased. Although a patient with acquired loss
      became severely ataxic, a patient with congenital loss did not show any ataxia at
      all. The present study suggests that vestibular cues are indispensable to the ego
      spatial relationship in the brain, and once the ego-spatial relationship becomes
      inadequate, discomfort acts as a safety device to brake uncontrollable actions.
      Then, perception of the outer world may automatically adjust voluntary actions by
      affecting motor commands. The importance of visual cues for representing an
      alternative framework may differ between congenital and acquired labyrinthine
      loss.

PMID- 9178224
TI  - The control of head movements during human balance corrections.
AB  - The assumption that the CNS regulates head stability during human balance
      corrections is explored in this review (an outgrowth of discussions initiated
      during the Head/Neck meeting held in Vail, Colorado, USA, July 1995). Two major
      questions were considered. First, how do the vestibulocollic (VCR) and
      cervicocollic (CCR) reflexes interact with intrinsic mechanical properties of the
      head neck system to control head position during balance corrections? Second, how
      is this interaction affected by factors such as vestibular loss, aging, and
      changes in behavioral goals or central set? The authors conclude that head
      velocities observed during balance corrections depend to a large extent on the
      movements of the head-neck mass-viscoelastic system whose properties could be
      altered by cocontracting the neck muscles. For experiments involving stance
      perturbations, much of the corrective response in neck muscles appeared to be
      triggered by trunk and leg proprioceptive signals, and a major role for the VCR
      was not established. Evidence consistent with a role for the vestibular system
      was found in other experimental paradigms in which the head was perturbed
      directly. In these paradigms the VCR modulates the amplitude of functionally
      stabilizing responses and damps mechanically induced instability of the head and
      neck.

PMID- 9178225
TI  - How to construct and move a cat's neck.
AB  - Extensive information has been accumulated over the past several years about the
      head-neck sensory-motor system, in particular that relating to cats. Using still
      x-ray and cineradiographic analysis, the skeletal geometry of head-neck posture
      in three dimensions--when an animal is resting, actively orienting, or locomoting
      -is described. From these descriptions, cervical, vertebral, and craniocervical
      joint biomechanics for all three rotational dimensions are quantified. These
      behavioral data on muscle and skeletal movements have been incorporated in a
      biomechanical, functional anatomical model of the head-neck movement system.
      Individual as well as groups of neck muscles have been measured in detail and
      their kinematics determined. The role of a number of these muscles will be
      described for several reflex and voluntary behavioral contexts, including muscle
      co-contractions. Having established how each movement is accomplished, the
      neuronal sensory-motor reflex basis of head-neck system stabilization in space is
      addressed. The vestibular system is largely responsible for acquisition and
      maintenance of upright posture. The bilateral semicircular canals (horizontal,
      anterior, posterior) and otoliths (sacculus, utriculus) feed information
      differentially to specific neck muscles: these connections are reviewed with
      regard to the origin of the reflex are from each receptor to its destination of
      specific muscles. Behavioral data from normal animals, and from animals whose
      vestibular receptor systems are selectively lesioned, will be reviewed to
      complement the functional interpretation of the sensory-motor transformations.
      Finally, the requirements for space-time coordinated cat head-neck movements will
      be synthesized, based on biomechanics, muscle kinematics, canal/otolith
      connectivity, and selective lesion experiments.

PMID- 9178226
TI  - A review of adaptive change in musculoskeletal impedance during space flight and
      associated implications for postflight head movement control.
AB  - We present a review of converging sources of evidence which suggest that the
      differences between loading histories experienced in 1-g and weightlessness are
      sufficient to stimulate adaptation in mechanical impedance of the musculoskeletal
      system. As a consequence of this adaptive change we argue that we should observe
      changes in the ability to attenuate force transmission through the
      musculoskeletal system both during and after space flight. By focusing attention
      on the relation between human sensorimotor activity and support surfaces, the
      importance of controlling mechanical energy flow through the musculoskeletal
      system is demonstrated. The implications of such control are discussed in light
      of visual-vestibular function in the specific context of head and gaze control
      during postflight locomotion. Evidence from locomotory biomechanics, visual
      vestibular function, ergonomic evaluations of human vibration, and specific
      investigations of locomotion and head and gaze control after space flight, is
      considered.

PMID- 9178227
TI  - Eye-head coordination toward auditory and visual targets in humans.
AB  - Eye-head coordination during gaze orientation toward auditory targets in total
      darkness has been examined in human subjects. The findings have been compared,
      for the same subjects, with those obtained by using visual targets. The use of
      auditory targets when investigating eye-head coordination has some advantages
      with respect to the more common use of visual targets: (i) more eccentric target
      positions can be presented to the subject; (ii) visual feedback is excluded
      during the execution of gaze displacement; (iii) complex patterns of saccadic
      responses can be elicited. This last aspect is particularly interesting for
      examining the coupling between the eyes and the head displacements. The
      experimental findings indicate that during gaze orientation toward a visual or an
      auditory target the central nervous system adopts the same strategy of using both
      the saccadic mechanism and the head motor plant. In spite of a common strategy,
      qualitative and quantitative parameters of the resulting eye-head coordination
      are slightly different, depending on the nature of the target. The findings
      relating to patterns of eye-head coordination seem to indicate a dissociation
      between the eyes and the head, which receive different motor commands
      independently generated from the gaze error signal. The experimental findings
      reported in this paper have been summarized in a model of the gaze control system
      that makes use of a gaze feedback hypothesis through the central reconstruction
      of the eye and head positions.

PMID- 9178228
TI  - Do infants have motor responses to sudden surface rotations in prone position?
AB  - This study investigated whether sudden rotation of the support surface (platform)
      triggers motor responses similar to reactions to sudden free fall in infants at
      very early age (2 to 5 weeks). Ten infants in prone position were exposed to
      sudden head-down rotation (mimicking the falling phase) and head-up rotation of
      the platform (mimicking landing phase) of 4 degrees or 6 degrees amplitude and 35
      degrees/s velocity while EMGs and kinematics were recorded from the neck, trunk,
      and right arm. One infant, reassessed at 13 weeks, and one adult were tested for
      complementary developmental information. Sudden downward acceleration of the
      platform, induced either during head-down rotation or during the deceleration
      phase of head-up rotation, indeed mimicked falling and evoked in infants two
      peaked EMG responses in the neck, trunk, and arm muscles, lasting in the latter
      over several hundred milliseconds. The activation pattern showed similarities to
      the adult and 13-week-old control subjects. The results suggested that the first
      burst may be ascribed to cutaneous pressure changes at the body and to vestibular
      signals triggering a startle-like response, whereas the second burst of the
      pattern in the arm is likely a candidate for an early substrate of the landing
      response normally seen during later stages of motor development. Head control
      appeared to be related more to its position with respect to the orientation of
      the trunk rather than to space in the infants and in the adult and might be due
      to the experimental paradigm, in which the surface accelerated away from the body
      and not, as during normal falling, when the body accelerates toward the support
      surface.

PMID- 9178230
TI  - Improved sensitivity to overlapping multiplet signals in in vivo proton
      spectroscopy using a multiecho volume selective (CPRESS) experiment.
AB  - A method for volume selective proton spectroscopy is presented based on a
      multiecho sequence with short refocusing interval tcp. It is demonstrated, that
      by appropriate choice of tcp on the order of 4-6 ms, signals from overlapping
      multiplets like the glutamine and glutamate (Glu/Gln) resonances in spectra of
      the human brain are considerably increased compared with a conventional PRESS
      volume selection scheme. Thus proton spectra from J-coupled multiplet signals can
      be acquired with TE on the order of 20-30 ms avoiding the baseline problems
      arising at shorter echo times due to broad resonances. This allows to selectively
      acquire spectra from substances with longer T2 without the confounding effects
      from J-coupling occurring in conventional volume selection techniques.

PMID- 9178229
TI  - MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human
      results.
AB  - Using a new method of xenon laser-polarization that permits the generation of
      liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results
      from the human chest and the first 129Xe spectroscopy results from the human
      chest and head have been obtained. With polarization levels of approximately 2%,
      cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3
      (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase
      resonances in spectra from the chest were detected. In spectra from the head, one
      prominent dissolved-phase resonance, presumably from brain parenchyma, was
      detected. With anticipated improvements in the 129Xe polarization system, pulse
      sequences, RF coils, and breathing maneuvers, these results suggest the
      possibility for 129Xe gas-phase imaging of the lungs with a resolution
      approaching that of current conventional thoracic proton imaging. Moreover, the
      results suggest the feasibility of dissolved-phase imaging of both the chest and
      brain with a resolution similar to that obtained with the gas-phase images.

PMID- 9178231
TI  - Evidence for 100% 13C NMR visibility of glucose in human skeletal muscle.
AB  - The accuracy of the measurement of total muscle glucose by in vivo 13C NMR
      spectroscopy was tested in five normal volunteers during a euglycemic [1
      13C]glucose infusion. The NMR visible concentration calibrated using an external
      reference was compared with that calculated from plasma glucose concentration,
      assuming that glucose remained extracellular. The NMR measurement always provided
      higher values than the calculation from plasma glucose: 0.51 +/- 0.035 (mean +/-
      SE) versus 0.38 +/- 0.005 mmol/liter of muscle on average. This systematic
      difference was interpreted as reflecting the presence of muscle glucose-6
      phosphate, co-resonating with free glucose. Thus, glucose appeared to be
      virtually 100% NMR visible in human skeletal muscle.

PMID- 9178232
TI  - Intracellular volume and apparent diffusion constants of perfused cancer cell
      cultures, as measured by NMR.
AB  - Diffusion NMR spectroscopy was used to study intracellular volume and apparent
      water diffusion constants in different cell lines (DU145, human prostate cancer;
      AT3, rat prostate cancer; MCF-7, human breast cancer; RIF-1, mouse fibrosacroma).
      The cells were grown on various matrices (collagen sponge, collagen beads,
      polystyrene beads) which enabled continuous growth in perfused high density cell
      culture suitable for NMR studies. In perfused cell systems, the attenuation of
      the water signal versus the squared gradient strength was fitted by the sum of
      two decaying exponentials. For the slowly decaying component the apparent water
      diffusion constant at 37 degrees C was 0.22 (+/-0.02) x 10(-9) s/m2 for all cell
      lines at diffusion times > 100 ms. It continuously increased up to 0.47 (+/-0.05)
      x 10(-9) s/m2 when the diffusion time was decreased to 8 ms, indicating
      restricted diffusion. No significant effect of the matrices was observed. The
      fractional volume of the slow component as determined from the biexponential
      diffusion curve correlated with the relative intracellular volume, as obtained
      from the cell density in the sample and the cell size as measured by light
      microscopy. Therefore, this simple NMR approach can be used to determine
      intracellular volume in perfused cell cultures suitable for NMR studies. Using
      this information in combination with spectroscopic data, changes in intracellular
      metabolite concentration can be detected even when the cellular volume is
      changing during the experiment. The apparent diffusion constant for the fast
      diffusing component varied with growth matrix, cell density and cell type and
      also showed the typical characteristics of restricted diffusion (increase of
      apparent diffusion constant with time).

PMID- 9178233
TI  - Effect of brain, body, and magnet bore temperatures on energy metabolism during
      global cerebral ischemia and reperfusion monitored by magnetic resonance
      spectroscopy in rats.
AB  - To record brain temperature for comparison with rectal and temporalis muscle
      temperatures in preliminary studies before MR spectroscopy experiments, a
      thermistor was inserted into the basal ganglia in eight anesthetized, ventilated,
      and physiologically monitored rats. The rats were placed in an MR spectrometer
      and subjected to 60 min of global cerebral ischemia and 2 h of reperfusion
      without radiofrequency (RF) pulsing. Body temperature was maintained at 37.5-38.0
      degrees C (normothermia) or 36.5-37.0 degrees C (mild hypothermia). Brain
      temperature during ischemia, which dropped to 31.9 +/- 0.3 (hypothermia) and 33.6
      +/- 0.5 degrees C (normothermia), correlated with temporalis muscle temperature
      (r2 = 0.92) but not with body or magnet bore temperature measurements. Ischemia
      reduced brain temperature approximately 1.7 degrees C in rats subjected to mild
      hypothermia (1 degree reduction of body temperature). Parallel MR spectroscopy
      experiments showed no significant difference in energy metabolites between
      normothermic and hypothermic rats during ischemia. However, the metabolic
      recovery was more extensive 20-60 min after the onset of reperfusion in
      hypothermic rats, although not thereafter (P < 0.05). Mild hypothermia speeds
      metabolic recovery temporarily during reperfusion but does not retard energy
      failure during global ischemia in rats.

PMID- 9178234
TI  - Quantitative lactate-specific MR imaging and 1H spectroscopy of skeletal muscle
      at macroscopic and microscopic resolutions using a zero-quantum/double-quantum
      coherence filter and SLIM/GSLIM localization.
AB  - Quantitative lactate imaging and spectroscopy were performed on phantoms and on
      electrically stimulated, excised frog skeletal muscle at macroscopic and
      microscopic resolutions. Lactate selectivity was achieved by use of a zero
      quantum/double-quantum coherence (ZQC/DQC) lactate filter, which suppressed all
      signals besides lactate, including water and lipid, to below noise level. Three
      dimensional lactate data sets were acquired in 1-3 h; one of these spatial
      dimensions was frequency-encoded and the other two were phase-encoded. High
      resolution images were reconstructed using the spectral localization by imaging
      (SLIM) and generalized SLIM (GSLIM) techniques. Lactate quantitation was achieved
      by employing an external lactate concentration standard and was verified by
      comparison to quantitative STEAM-localized and nonlocalized spectra that used
      total creatine as an internal concentration reference. Additionally,
      quantitatively accurate behavior of the SLIM and GSLIM techniques as applied to
      data sets of low signal-to-noise ratio and to macroscopically heterogeneous
      objects was verified using simulations and real muscle lactate data sets with
      known heterogeneity.

PMID- 9178236
TI  - In vivo measurement of regional brain metabolic response to hyperventilation
      using magnetic resonance: proton echo planar spectroscopic imaging (PEPSI).
AB  - A new rapid spectroscopic imaging technique with improved sensitivity and lipid
      suppression, referred to as Proton Echo Planar Spectroscopic Imaging (PEPSI), has
      been developed to measure the 2-dimensional distribution of brain lactate
      increases during hyperventilation on a conventional clinical scanner equipped
      with a head surface coil phased array. PEPSI images (nominal voxel size: 1.125
      cm3) in five healthy subjects from an axial section approximately 20 mm inferior
      to the intercommissural line were obtained during an 8.5-min baseline period of
      normocapnia and during the final 8.5 min of a 10-min period of capnometry
      controlled hyperventilation (end-tidal PCO2 of 20 mmHg). The lactate/N-acetyl
      aspartate signal increased significantly from baseline during hyperventilation
      for the insular cortex, temporal cortex, and occipital regions of both the right
      and left hemisphere, but not in the basal ganglia. Regional or hemispheric right
      to-left differences were not found. The study extends previous work using single
      voxel MR spectroscopy to dynamically study hyperventilation effects on brain
      metabolism.

PMID- 9178237
TI  - A flexible magnetization transfer line shape derived from tissue experimental
      data.
AB  - To summarize and compare magnetization transfer data from biological tissues, a
      method was developed to extract the average absorption lineshape of the semi
      solid pool directly from magnetization transfer experimental data along with the
      four other parameters that characterize the two-pool model of exchange.
      Magnetization transfer data for several biological tissues were analyzed using
      this method and the resulting "flexible" lineshapes were compared with super
      Lorentzian and "Kubo-Tomita" lineshapes. The use of flexible lineshapes
      noticeably improves the fit of the two-pool model to the data. The derived
      flexible lineshapes of all the tissues analyzed are physically realistic and show
      remarkably consistent behavior.

PMID- 9178238
TI  - An MRI method for measuring T2 in the presence of static and RF magnetic field
      inhomogeneities.
AB  - A magnetic resonance imaging method for measuring the T2 relaxation time constant
      is proposed. It is based on the assumption that, under very general conditions,
      the MR signal near a spin echo has a special symmetry arising from the refocusing
      nature of the 180 degrees RF pulse. A gradient echo sampling of the spin echo
      (GESSE) sequence is implemented to evaluate T2 by collecting multiple gradient
      echoes before and after the spin echo. This approach is a modification of the
      GESFIDE sequence proposed by Ma and Wehrli. However, our approach compares images
      that are not separated by any RF pulses and, as a result, is insensitive to slice
      profile imperfections. In addition, the calculated T2 value does not rely on any
      special assumptions about the MRI signal behavior in the presence of an
      inhomogeneous static magnetic field and, hence, is insensitive to the presence of
      static magnetic field inhomogeneities.

PMID- 9178235
TI  - Effects of severe global ischemia on N-acetylaspartate and other metabolites in
      the rat brain.
AB  - N-acetylaspartate (NAA) is found exclusively in neurons and their processes in
      the adult brain. Since the regional distribution of NAA may be imaged using
      magnetic resonance spectroscopic imaging (1H-MRSI), a regional measure of
      neuronal density may be noninvasively obtained. The technique may be particularly
      useful in the diagnosis of diseases where neurons are selectively injured, since
      these diseases do not result in definitive changes on conventional imaging
      studies. The goal of this study was to determine whether 1H-MRSI measurement of
      NAA defects neuronal loss following global ischemia. 1H-MRSI was performed in
      rats 24 h after global ischemia was induced by bilateral carotid occlusion plus
      hypotension. 1-H-MRSI showed that NAA was decreased by 28-74% in vulnerable
      regions, including the cortex, striatum, hippocampus, and, to a lesser extent,
      the thalamus. No change was observed in the brain stem or cerebellum. Regions
      where 1H-MRSI observed NAA was decreased also had histological evidence of
      selective neuronal necrosis and showed marked increase of lactate and alanine.
      These results show that 1H-MRSI detected loss of NAA in brain regions with
      selective neuronal loss, suggesting that 1H-MRSI measurements of NAA could detect
      neuronal loss in a variety of disease states where there is selective neuronal
      necrosis.

PMID- 9178239
TI  - Evaluation of the early response in fMRI in individual subjects using short
      stimulus duration.
AB  - Optical imaging studies have provided evidence of an initial increase in
      deoxyhemoglobin following the onset of neuronal stimulation/activation and
      demonstrated that this initial increase could be spatially more specific to the
      site of neuronal activity. These studies also raised the possibility of improving
      the specificity of fMRI by selective mapping of this early response. Previous MR
      studies reported the observation of this early response but were limited in scope
      and not in full agreement. This paper presents a more extensive study that (a)
      demonstrates the initial signal decrease in individual subjects and (b) examines
      its dependence on stimulus duration and subject. Binocular visual stimulation
      experiments were performed on 14 subjects using echo-planar imaging (EPI) with
      high temporal resolution. An initial signal decrease was consistently observed in
      regions that were more localized than those displaying the delayed positive
      response. In agreement with previous fMRI and optical imaging findings, the
      maximum signal decrease was 1-2% and occurred at approximately 2 s after the
      onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s,
      the temporal dynamics and the amount of signal change of the early response was
      essentially independent of the stimulus duration, while the delayed response and
      the post-stimulus undershoot increased both in terms of magnitude and rise time
      as the duration of the stimulus increased; this observation is concordant with
      the recent optical imaging study.

PMID- 9178240
TI  - Dynamic liver imaging with iron oxide agents: effects of size and biodistribution
      on contrast.
AB  - In vivo effective relaxation rates in normal rat liver were evaluated for four
      dextran coated iron oxide agents: monocrystalline iron oxide nanocolloid (MION)
      with a mean particle diameter of 3.9 nm, a polycrystalline agent (PION) with a
      larger mean diameter of 12 nm, and these two agents labeled with the asialofetuin
      (ASF) protein for high hepatocytic receptor binding affinity (MION-ASF and PION
      ASF). Using echo planar imaging at 2 Tesla, dose response was measured with
      measured with high temporal resolution for 3 h after injection of agent, and by
      comparing with relaxivities in vitro and in brain, dominant in vivo contrast
      phenomena were elucidated. While transverse relaxivity for PION-ASF exceeded that
      for MION-ASF by almost a factor of 2 in solution, relaxation rates in vivo became
      equivalent. Liver relaxation using non-ASF agents was consistent with rapid water
      exchange between vascular and extravascular compartments, which dominated
      relaxation as a result of agent accumulation in Kupffer cells.

PMID- 9178241
TI  - Guidewire antennas for MR fluoroscopy.
AB  - Before MRI can be used for guiding vascular interventions, the problem of
      dependably visualizing guidewires must be solved. Ideally, the position and
      curvature of the tip of the guidewire should be visible to facilitate steering
      through the vascular system. In this paper, various antennas are described that
      can be incorporated into a guidewire tip. These antennas allow the guidewire to
      be visualized with high contrast. Computer simulation and experimental evidence
      are presented showing the value of adding a passive MR signal source, with a
      short T1, internal to the coil. The internal source increases the available
      signal, narrows the apparent width of the guidewire, and allows the use of fast
      imaging sequences.

PMID- 9178242
TI  - Background suppression with multiple inversion recovery nulling: applications to
      projective angiography.
AB  - We have developed a technique to accurately null the longitudinal magnetization
      (Mz) of background material. This suppression involves first saturating the
      longitudinal magnetization (Mz) of a region, and then applying several
      nonselective inversions. The inversions are timed relative to the saturation such
      that Mz is nulled across a broad range of T1 at a predetermined time after the
      initial saturation. B1 and B0 inhomogeneity, which could lead to inaccurate
      suppression, are dealt with by the combination of a multiple tip saturation
      sequence and four adiabatic inversion pulses. The suppression sequence can be
      used to form projective angiograms by selectively tagging the imaging region with
      the saturation pulse. After the inversions are played out, a projection taken
      through the tag region when Mz is nulled will only contain signal from blood that
      has flown into the region after the saturation. Since only two dimensions are
      acquired, the technique can acquire gated projection angiograms in reasonable
      scan times. Representative inflow MIR angiograms of the carotid arteries and
      renal arteries show excellent background suppression.

PMID- 9178243
TI  - Improved automatic off-resonance correction without a field map in spiral
      imaging.
AB  - Non-2DFT k-space readout strategies are useful in fast imaging but prone to
      blurring when reconstructed off resonance. Field inhomogeneities or
      susceptibility variations, coupled with a long readout time, are the major
      sources of this artifact. Correction methods based on a priori off-resonance
      information such as an acquired field map have been proposed in the literature.
      An alternative approach estimates the spatially varying off-resonance frequency
      from the data itself before applying a correction. In this latter approach there
      is a trade-off between the extent of correction and the chance of increased
      artifact due to estimation error. This paper introduces an improved algorithm for
      field map estimation which is both faster and more robust than the existing
      method. It uses a multi-stage estimation of the field map, starting from a coarse
      estimate both in frequency and space and proceeds towards higher resolution. The
      new algorithm is applied to phantom and in vivo images acquired with radial and
      spiral sequences to give sharper images.

PMID- 9178244
TI  - Improved vessel visualization in MR angiography by nonlinear anisotropic
      filtering.
AB  - This paper deals with a preprocessing technique of magnetic resonance angiography
      (MRA) images, applied before maximum-intensity-projection (MIP). The purpose was
      to recover small low-intensity vessels, visible in individual slices, but lost in
      MIP images that usually have higher background level than the individual slices.
      The authors have developed a nonlinear three-dimensional spatial filtering
      technique (called HD filter) based on anisotropic smoothing. The filter first
      searches for the local orientation of the vessel. It then performs a nonlinear
      smoothing in the vessel's local direction so as to avoid blurring its boundaries.
      Noise level reduction, contrast enhancement, and improved small vessel visibility
      achieved by this filter are illustrated on dynamic contrast-enhanced subtraction
      MRA images of the lower limbs.

PMID- 9178245
TI  - Excitation of arbitrary shapes by gradient optimized random walk in discrete k
      space.
AB  - A new technique for the excitation of arbitrary shapes is proposed. It is based
      on a parallel sequence of small tip angle RF pulses and gradient pulses. The
      small tip angle rotations co-add yielding a 90 degrees excitation pulse within
      the selected excitation profile while outside the profile, the rotations cancel
      each other. A full theory of the completely arbitrary regional volume excitation
      (CARVE) method is presented and experimentally verified. In CARVE, k-space is
      discrete because the RF is applied in pulses. The discrete character of k-space
      permits an arbitrary trajectory for the k-space walk. The optimal random
      trajectory is found by minimizing the gradient load using simulated annealing. It
      is shown, both theoretically and experimentally, that such a trajectory is much
      better than any other systematic or random trajectory in k-space.

PMID- 9178246
TI  - Reduction of geometric and intensity distortions in echo-planar imaging using a
      multireference scan.
AB  - Echo-planar imaging (EPI) is very sensitive to patient-induced field
      inhomogeneity caused by susceptibility changes between different anatomical
      regions. This results in geometric and intensity distortions in the image,
      especially near tissue/air and tissue/bone interfaces. A new approach is
      presented to reduce geometric and intensity distortions in EPI. A phase-encoded
      multireference scan is used to estimate the amplitude and phase errors in the
      measured signals due to the field inhomogeneity. The EPI data is corrected using
      both the amplitude and phase of the measured errors. This technique has been
      evaluated using EPI pulse sequences implemented with conventional gradients and
      implemented with imaging systems that have special resonating gradients and fast
      analog to digital converters. The results in both phantom and human studies show
      that in the absence of object motion the new correction technique can effectively
      reduce the geometric and intensity distortions.

PMID- 9178247
TI  - The use of active shape models for making thickness measurements of articular
      cartilage from MR images.
AB  - Previously reported studied to quantify articular cartilage have used labor
      intensive manual or semi-automatic data-driven techniques, demonstrating high
      accuracy and precision. However, none has been able to automate the segmentation
      process. This paper describes a fast, automatic, model-based approach to
      segmentation and thickness measurement of the femoral cartilage in 3D T1-weighted
      images using active shape models (ASMs). Systematic experiments were performed to
      assess the accuracy and precision of the technique with in vivo images of both
      normal and abnormal knees. Segmentation accuracy was determined by comparing the
      results of the segmentation with the boundaries delineated by a radiologist. The
      mean error in locating the boundary was 0.57 pixels. To assess the precision of
      the measurement technique, the mean thickness of the femoral cartilage was
      calculated for repeated scans of five healthy volunteers. A mean coefficient of
      variation (CV) of 2.8% was obtained for the thickness measurements.

PMID- 9178248
TI  - Physiologic basis for BOLD MR signal changes due to hypoxia/hyperoxia: separation
      of blood volume and magnetic susceptibility effects.
AB  - An NMR method is presented for separating blood volume and magnetic
      susceptibility effects in response to respiratory challenges such as hypoxia and
      hyperoxia. The technique employs high susceptibility contrast agents to enhance
      blood volume induced signal changes. The results show that for a rat model the
      dominant source of signal variation upon changing breathing gas from 100% oxygen
      to 10% oxygen/90% nitrogen is the change in blood magnetic susceptibility
      associated with the BOLD effect. The results imply that signal changes associated
      with respiratory challenges can be regarded as indicators of local blood
      oxygenation in vivo.

PMID- 9178249
TI  - Dispersion in magnetization transfer contrast at a given specific absorption rate
      due to variations of RF pulse parameters in the magnetization transfer
      preparation.
AB  - The effects of RF pulse parameters on magnetization transfer contrast (MTC) were
      investigated using a magnetization prepared segmented fast gradient echo
      sequence. MTC was found not to be uniquely determined by the specific absorption
      rate (SAR). RF pulse parameters (RF amplitude, number of RF pulses and RF
      duration) also affect MTC. There can be 40% variation in MTC due to differences
      in RF parameters at SAR = 1 W/kg for a 70-kg subject. Increasing the number of RF
      pulses is a more efficient way to increase MTC than increasing RF amplitude. This
      phenomenon is likely caused by the fact that the time scale for magnetization
      transfer between the free and restricted proton pools is on the same order or
      longer than the duration of the MT pulse. Accordingly, increase in the MT pulse
      duration by increasing the number of RF pulses in the MT pulse allows more
      effective magnetization transfer. Such information can be used as a guide to
      select RF pulse parameters for a magnetization transfer (MT) pulse. An off
      resonance MT pulse designed under this guide for coronary MR angiography improved
      the depiction of distal vessels.

PMID- 9178250
TI  - Catheter tracking using continuous radial MRI.
AB  - The guidance of minimally invasive procedures may become a very important future
      application of MRI. The guidance of interventions requires images of the anatomy
      as well as the information of the position of invasive devices used. This paper
      introduces continuous radial MRI for the simultaneous acquisition of the anatomic
      MR image and the position of one or more small RF-coils (mu-coils), which can be
      mounted on invasive devices such as catheters or biopsy needles. This approach
      allows the in-plane tracking of an invasive device without any prolongation of
      the overall acquisition time. The extension to three-dimensional position
      tracking is described. Phantom studies are presented demonstrating the capability
      of this technique for real-time automatic adjustment of the slice position to the
      current catheter position with a temporal resolution of 100 ms. Simultaneously
      the in-plane catheter position is depicted in the actually acquired MR image
      during continuous scanning.

PMID- 9178251
TI  - Functional magnetic resonance imaging of median nerve stimulation in rats at 2.0
      T.
AB  - An animal model of sensory activation using fMRI at 2.0 T has been developed,
      demonstrating that fMRI studies on animals need not be limited to high field
      magnets. These methods produced reliable image intensity changes of 2% using
      median nerve stimulation in rats at 3 Hz and propofol as the anesthetic agent. At
      6 Hz the activation was slightly but not statistically significantly greater. The
      feasibility of fMRI studies in animals using propofol suggests that it may be a
      useful anesthetic for fMRI studies in agitated adult patients or in children.

PMID- 9178252
TI  - The Pbx family of proteins is strongly upregulated by a post-transcriptional
      mechanism during retinoic acid-induced differentiation of P19 embryonal carcinoma
      cells.
AB  - Retinoic acid (RA) induces expression of genes encoding the Hox family of
      transcription factors, whose differential expression orchestrates developmental
      programs specifying anterior-posterior structures during embryogenesis. Hox
      proteins bind DNA as monomers and heterodimers with Pbx proteins. Here we show
      that RA upregulates Pbx protein abundance coincident with transcriptional
      activation of Hox genes in P19 embryonal carcinoma cells undergoing neuronal
      differentiation. However, in contrast to Hox induction, Pbx upregulation is
      predominantly a result of post-transcriptional mechanisms. Interestingly, Pbx1,
      Pbx2, and Pbx3 exhibit different profiles of upregulation, suggesting possible
      functional divergence. The parallel upregulation of Pbx and Hox proteins in this
      model suggests an important role for transcriptional control by Pbx-Hox
      heterodimers during neurogenesis, and argues for precise control by RA.

PMID- 9178253
TI  - A role for notochord in axial vascular development revealed by analysis of
      phenotype and the expression of VEGR-2 in zebrafish flh and ntl mutant embryos.
AB  - The notochord is required for the differentiation of nearby tissues, including
      the neural tube and the floor plate. Because the dorsal aorta and axial vein are
      midline structures, their development might also be influenced by the notochord.
      To investigate this possibility, we cloned zebrafish VEGR-2, homologous to the
      earliest known marker of endothelial cells in mammals. In flh and ntl mutant
      embryos, which lack a notochord, we found a defect in axial blood vessel
      formation, and a delay in the fusion of VEGR-2 positive endothelial progenitor
      cells into the primary vascular plexus and a block in the establishment of mature
      vessels. Differences in the vascular phenotype between the two mutations
      correlated with the severity of their axial mesodermal defects. These
      observations support a role for the notochord in vasculogenesis.

PMID- 9178254
TI  - Cloning and expression analysis of a novel mouse gene with sequence similarity to
      the Drosophila fat facets gene.
AB  - The Drosophila fat facets (faf) gene is a ubiquitin-specific protease necessary
      for the normal development of the eye and of the syncytial stage embryo in the
      fly. Using a gene trap approach in embryonic stem cells we have isolated a murine
      gene with extensive sequence similarity to the Drosophila faf gene and called it
      Fam (fat facets in mouse). The putative mouse protein shows colinearity and a
      high degree of sequence identity to the Drosophila protein over almost its entire
      length of 2554 amino acids. The two enzymatic sites characteristic of ubiquitin
      specific proteases are very highly conserved between mice and Drosophila and this
      conservation extends to yeast. Fam is expressed in a complex pattern during
      postimplantation development. In situ hybridisation detected Fam transcripts in
      the rapidly expanding cell populations of gastrulating and neurulating embryos,
      in post-mitotic cells of the CNS as well as in the apoptotic regions between the
      digits, indicating that it is not associated with a single developmental or
      cellular event. The strong sequence similarity to faf and the developmentally
      regulated expression pattern suggest that Fam and the ubiquitin pathway may play
      a role in determining cell fate in mammals, as has been established for
      Drosophila.

PMID- 9178255
TI  - The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4.
AB  - Specific signaling molecules play a pivotal role in the induction and
      specification of tissues during early vertebrate embryogenesis. BMP-4 specifies
      ventral mesoderm differentiation and inhibits neural induction in Xenopus,
      whereas three molecules secreted from the organizer, noggin, follistatin and
      chordin dorsalize mesoderm and promote neural induction. Here we report that
      follistatin antagonizes the activities of BMP-4 in frog embryos and mouse
      teratocarcinoma cells. In Xenopus embryos follistatin blocks the ventralizing
      effect of BMP-4. In mouse P19 cells follistatin promotes neural differentiation.
      BMP-4 antagonizes the action of follistatin and prevents neural differentiation.
      In addition we show that the follistatin and BMP-4 proteins can interact directly
      in vitro. These data provide evidence that follistatin might play a role in
      modulating BMP-4 activity in vivo.

PMID- 9178256
TI  - HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely
      related to hypoxia-inducible factor-1 alpha and developmentally expressed in
      blood vessels.
AB  - Transcription factors of the bHLH-PAS protein family are important regulators of
      developmental processes such as neurogenesis and tracheal development in
      invertebrates. Recently a bHLH-PAS protein, named trachealess (trl) was
      identified as a master regulator of tracheogenesis. Hypoxia-inducible factor, HIF
      1 alpha, is a vertebrate relative of trl which is likely to be involved in growth
      of blood vessels by the induction of vascular endothelial growth factor (VEGF) in
      response to hypoxia. In the present study we describe mRNA cloning and mRNA
      expression pattern of mouse HIF-related factor (HRF), a novel close relative of
      HIF-1 alpha which is expressed most prominently in brain capillary endothelial
      cells and other blood vessels as well as in bronchial epithelium in the embryo
      and the adult. In addition, smooth muscle cells of the uterus, neurons, brown
      adipose tissue and various epithelial tissues express HRF mRNA as well. High
      expression levels of HRF mRNA in embryonic choroid plexus and kidney glomeruli,
      places where VEGF is highly expressed, suggest a role of this factor in VEGF gene
      activation similar to that of HIF-1 alpha. Given the similarity between
      morphogenesis of the tracheal system and the vertebrate vascular system, the
      expression pattern of HRF in the vasculature and the bronchial tree raises the
      possibility that this family of transcription factors may be involved in
      tubulogenesis.

PMID- 9178257
TI  - The dynamics of neurogenic signalling underlying bristle development in
      Drosophila melanogaster.
AB  - We have examined expression of the neurogenic gene, Delta (Dl), and the
      regulatory relationships between the Delta-Notch signalling pathway and the
      proneural gene, achaete, during microchaeta development in Drosophila. Delta is
      expressed in all microchaeta proneural cells and microchaeta sensory organ
      precursors (SOPs) and is expressed dynamically in SOP progeny. We find that Delta
      expression in microchaeta proneural cells is detected prior to the onset of
      achaete expression and arises normally in the absence of achaete/scute function,
      indicating that initial Delta expression in the notum is not dependent on
      proneural gene function. Activation of the Delta-Notch pathway results in loss of
      Delta protein accumulation, suggesting that Delta expression is regulated, in
      part, by Delta-Notch signalling activity. We find that Delta signalling is
      required for correct delineation of early proneural gene expression in developing
      nota. Within microchaeta proneural stripes, we demonstrate that Delta-Notch
      signalling prohibits adoption of the SOP fate by repressing expression of
      proneural genes.

PMID- 9178258
TI  - Lethal of scute requires overexpression of daughterless to elicit ectopic
      neuronal development during embryogenesis in Drosophila.
AB  - Classical genetics indicates that the achaete-scute gene complex (AS-C) of
      Drosophila promotes development of neural progenitor cells. To further analyze
      the function of proneural genes, we have studied the effects of Gal4-mediated
      expression of lethal of scute, a member of the AS-C, during embryogenesis.
      Expression of lethal of scute forces progenitor cells of larval internal sensory
      organs, which are normally committed to this fate independently of the activity
      of the AS-C, to take on features of external sensory organs. Supernumerary neural
      cells can be induced ectopically only if daughterless is overexpressed, either
      alone or together with lethal of scute: cells of the amnioserosa and the hindgut
      then express neuronal markers. Furthermore, cells of the proctodeal anlage, which
      normally lack neural competence, acquire the ability to develop as neuroblasts
      following transplantation into the neuroectoderm. We show here that activated
      Notch prevents the cells of the neuroectoderm from forming extra neural tissue
      when they express an excess of proneural proteins. Under the present conditions,
      lateral inhibition is thus dominant over the activity of proneural genes.

PMID- 9178259
TI  - Spatial and temporal pattern of expression of the wingless and engrailed genes in
      the adult antenna is regulated by age-dependent mechanisms.
AB  - The spatial and temporal pattern of expression of enhancer trap lines reporting
      on the wingless (wg) and engrailed (en) genes was characterized in the adult
      antenna of Drosophila melanogaster. The time courses of expression seen for wg
      and en, although different from each other, reveal a complex well-controlled
      pattern of temporal expression, providing evidence that regulatory mechanisms are
      preserved throughout the life span of the adult fly. Altering the life span
      demonstrates that the temporal patterns of expression of both wg and en are
      linked to life span. These studies suggest that the expression of wg and en in
      the adult antenna is controlled by age-dependent mechanisms.

PMID- 9178260
TI  - Transcription regulation and alternative splicing of an early zygotic gene
      encoding two structurally distinct zinc finger proteins in Xenopus laevis.
AB  - We describe the structural organization of a gene, termed XFDL 141/156, that is
      transiently activated during early Xenopus development. XFDL 141/156 is first
      transcribed at the midblastula transition (MBT) and during early gastrulation
      events. A roughly 200 nucleotide fragment immediately 5' to the transcription
      start site is sufficient for transient, early zygotic activation of gene
      expression. The primary transcript is subject to alternative splicing.
      Corresponding cDNAs encode two structurally related but completely distinct C2H2
      type zinc finger proteins of unknown biological function.

PMID- 9178261
TI  - Fritz: a secreted frizzled-related protein that inhibits Wnt activity.
AB  - Signaling molecules of the Wnt gene family are involved in the regulation of
      dorso-ventral, segmental and tissue polarity in Xenopus and Drosophila embryos.
      Members of the frizzled gene family, such as Drosophila frizzled-2 and rat
      frizzled-1, have been shown encode Wnt binding activity and to engage
      intracellular signal transduction molecules known to be part of the Wnt signaling
      pathway. Here we describe the cloning and characterization of Fritz, a mouse
      (mfiz) and human (hfiz) gene which codes for a secreted protein that is
      structurally related to the extracellular portion of the frizzled genes from
      Drosophila and vertebrates. The Fritz protein antagonizes Wnt function when both
      proteins are ectopically expressed in Xenopus embryos. In early gastrulation,
      mouse fiz mRNA is expressed in all three germ layers. Later in embryogenesis fiz
      mRNA is found in the central and peripheral nervous systems, nephrogenic
      mesenchyme and several other tissues, all of which are sites where Wnt proteins
      have been implicated in tissue patterning. We propose a model in which Fritz can
      interfere with the activity of Wnt proteins via their cognate frizzled receptors
      and thereby modulate the biological responses to Wnt activity in a multitude of
      tissue sites.

PMID- 9178262
TI  - Camguk, Lin-2, and CASK: novel membrane-associated guanylate kinase homologs that
      also contain CaM kinase domains.
AB  - MAGUKs (membrane-associated guanylate kinase homologs) are proteins involved in
      cell junction organization, tumor suppression, and signalling. Their structure
      includes one or three copies of a DHR or PDZ domain (discs-large homologous
      region or PSD-95/SAP90, discs-large ZO-1 homologous domain), an SH3 domain, and a
      guanylate kinase domain. MAGUKs were classified into two subfamilies: Dlg-like
      with three DHR/PDZ domains and p55-like with a single DHR/PDZ domain. There is
      now a new subfamily whose members have a novel domain structure: a
      calcium/calmodulin-dependent protein kinase domain in the N-terminus as well as
      the DHR/PDZ, SH3 and GUK domains in the C-terminus. These new MAGUKs may regulate
      transmembrane molecules that bind calcium, calmodulin, or nucleotides, camguk
      (cmg) is a Drosophila member of this novel MAGUK subfamily; we report its
      sequence and domain structure.

PMID- 9178263
TI  - The identification and molecular characterization of Trypanosoma cruzi amastigote
      surface protein-1, a member of the trans-sialidase gene super-family.
AB  - An accumulating body of evidence suggests that T. cruzi-infected host cells are
      recognized and destroyed by class I major histocompatibility complex (MHC)
      restricted CD8+ T-cells thus contributing to immune control of the infection [1
      6]. However, to date, only a few amastigote proteins which could be the target of
      this response have been described and gene sequence information is available only
      for the amastins [7]. In order to identify amastigote proteins which could
      contribute to immune detection of infected host cells, a panel of monoclonal
      antibodies specific for amastigote proteins was produced and screened. Three mAbs
      (IIIC4, VIIC1 and IIID4) were identified which recognized amastigote surface
      proteins of 78, 26 and 53 kDa, respectively. Screening of an amastigote cDNA
      expression library with mAb IIIC4 resulted in the isolation of a 2.8 Kb clone.
      pSI2. The derived amino acid sequence indicates that the pSI2 clone encodes an
      amastigote surface protein belonging to the T. cruzi trans-sialidase super
      family. Based on its preferential expression in the amastigote stage we have
      named this protein amastigote surface protein-1 (ASP-1). ASP-1 contains the third
      and fourth Asp block motifs, SxDxGxTW and the fibronectin type III-like domain,
      VTVxNVxLYNR, thus placing it in family II of the T. cruzi trans-sialidases [8].
      ASP-1 is the first trans-sialidase family member shown to be preferentially
      expressed in the amastigote stage of the T. cruzi life cycle. This expression of
      ASP-1 on parasites in infected cells and its apparent membrane attachment by a
      glycosylphosphatidylinositol (GP1)-anchor makes it a prime candidate to enter the
      class I MHC processing and presentation pathway.

PMID- 9178264
TI  - Primary structure and biochemical properties of a variant-specific surface
      protein of Giardia.
AB  - Trophozoites of Giardia duodenalis express at their cell surface variant-specific
      proteins (VSPs) that are believed to contribute to the protection of the parasite
      from immunological and other host defense mechanisms. In the present study, we
      have cloned and characterized the gene encoding a VSP (VSP4A1, originally
      designated CRISP-90) that is expressed by the sheep-derived Giardia variant clone
      O2-4A1. The gene was isolated by probing a genomic library with a near-full
      length gene-specific polymerase chain reaction (PCR) product. The VSP4A1 gene
      specifies a 70729 Da protein with features common to all previously reported
      VSPs, including a high cysteine and threonine content, a highly conserved
      hydrophobic carboxy-terminal domain and little similarity in the remaining
      polypeptide sequence. Comparison of the predicted sequence with the amino
      terminal sequence of purified VSP4A1 revealed the absence of an amino-terminal
      hydrophobic extension from the mature protein. VSP4A1 purified from the O2-4A1
      variant clone was found to undergo conformational changes resulting in the
      formation of two additional electrophoretic species. Free thiol groups were not
      detected in purified VSP4A1, indicating that all cysteine residues may be
      involved in disulphide crosslinking. Possibly as a consequence of this VSP4A1 was
      found to be fairly resistant to proteolytic digestion. Although VSP4A1 is able to
      bind zinc following blotting to a nitrocellulose membrane, other analyses with
      both the purified and cell associated VSP have failed to confirm significant zinc
      ion binding to this protein. The latter result questions the assumption
      previously made by other authors that zinc binding to VSPs constitutes an
      important structural and functional aspect of these proteins.

PMID- 9178265
TI  - Expression of Toxoplasma gondii genes in the closely-related apicomplexan
      parasite Neospora caninum.
AB  - We have established the feasibility of using Neospora caninum as a heterologous
      system for the expression of genes from the closely-related parasite Toxoplasma
      gondii. Plasmid construct containing the lacZ gene from Escherichia coli driven
      by T. gondii promoters were electroporated into N. caninum parasites, and
      expression of beta-galactosidase (beta-Gal) activity was assayed enzymatically.
      In transient assays, expression of beta-Gal driven by the GRA1 promoter was
      approximately 10-fold higher than the expression obtained with the SAG1 promoter.
      Enzyme activity was not detected when N. caninum parasites were transfected with
      a promoterless lacZ construct. Transfection of N. caninum with complete genomic
      clones of SAG1 or GRA2 from T. gondii yielded parasites that transiently
      expressed the respective gene products, as detected by immunofluorescence and
      Western blot. Additionally, these transiently expressed T. gondii proteins
      appeared by immunofluorescence localization and Triton X-114 partitioning to be
      correctly targeted in both extracellular and intracellular N. caninum parasites.
      Heterologous gene expression should be useful for studying the function of
      specific gene products and may facilitate the identification of genes responsible
      for the phenotypic differences observed between these two closely-related
      apicomplexan parasites.

PMID- 9178266
TI  - Isolation and molecular characterization of the bifunctional
      hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase gene from
      Toxoplasma gondii.
AB  - Toxoplasma gondii is an important cause of AIDS-related opportunistic infection,
      manifest as toxoplasmic encephalitis. The clinical treatment of choice is the
      synergistic combination of antifolate agents, pyrimethamine and sulphadiazine, of
      which the latter targets the parasite's dihydropteroate synthase (DHPS) activity.
      Here, we describe the isolation of the gene encoding this activity in T. gondii.
      The nucleotide sequence contains an open reading frame interrupted by five
      introns, which encodes a protein of 664 amino acids with an M(r) of 72991.
      Sequence analysis revealed that, in addition to DHPS, the predicted protein
      contains a second enzyme function, hydroxymethyldihydropterin pyrophosphokinase
      (PPPK). This enzyme immediately precedes DHPS in the folate biosynthetic pathway.
      The bifunctional arrangement of the T. gondii pppk-dhps gene is the same as that
      observed in the related protozoan parasite, Plasmodium falciparum, and confirms
      previous biochemical data that these activities were inseparable. Recently,
      specific mutations within conserved motifs of the DHPS gene of P. falciparum have
      been identified which give rise to sulphonamide drug resistance. Analysis of
      seven clinical isolates of T. gondii did not reveal any similar mutations in this
      limited sample of organisms that had been subjected to drug pressure.

PMID- 9178267
TI  - Host urokinase-type plasminogen activator participates in the release of malaria
      merozoites from infected erythrocytes.
AB  - Malaria infection of red blood cells is associated with plasminogen activation.
      Surface immunofluorescence and immunoprecipitation experiments, using specific
      polyclonal and monoclonal antibodies raised against human urokinase, demonstrate
      that this activity is due to the binding of host urokinase-type plasminogen
      activator to the surface of erythrocytes infected by mature forms of Plasmodium
      falciparum malaria parasites. Depletion of urokinase from the culture medium
      leads to the inhibition of merozoite release and the accumulation of segmenter
      infected erythrocytes; this inhibition is reversed by the addition of human
      single-chain or two-chain urokinase. These findings are consistent with host
      urokinase being involved in the process of merozoite release from the red blood
      cell.

PMID- 9178268
TI  - Molecular characterization of myosin IB from the lower eukaryote Entamoeba
      histolytica, a human parasite.
AB  - The complete amino acid sequence of the Entamoeba histolytica unconventional
      myosin IB (Eh-myosin IB) is reported. Sequencing of overlapping cDNA fragments
      reveals a single open reading frame which predicts a 130 kDa protein of 1049 aa.
      Eh-myosin IB presents the three characteristics domains of myosins I subclass 1.
      This protein presents homology with myosins IB from other amoebae, but striking
      homologies with vertebrate unconventional myosins were also observed. The
      predicted actin and ATP-binding sites are located in the head domain. The heavy
      chain phosphorylation region is homologous to metazoan myosins I with an acidic
      residue present at the phosphorylation site. In the neck domain, an IQ motif
      indicates potential binding of calmodulin to the myosin I heavy chain. In the
      tail of Eh-myosin IB the three characteristic regions of myosin I are found. A
      putative membrane binding domain a very short domain rich in alanine and proline
      we demonstrate to be functional for actin binding, and the src-homology 3 domain.
      The Entamoeba histolytica myosin IB is the first unconventional myosin so far
      described in a lower eukaryote.

PMID- 9178269
TI  - Sequence analysis of a gene family encoding Taenia ovis vaccine antigens
      expressed during embryogenesis of eggs.
AB  - The 45W vaccine antigen of the cestode parasite Taenia ovis is a member of a
      small gene family estimated to comprise six members. All six genes were cloned
      and characterised. Nucleotide sequence analysis of the different family members
      identified a set of closely related genes exhibiting between 75.2 and 98.6% DNA
      sequence homology. Intron/exon structure for the various genes constituting the
      family was found to be conserved. Open reading frame analysis and pairwise
      alignments of predicted polypeptides from the various members of the family
      revealed that the encoded proteins share between 51.8 and 96.5% amino acid
      identity with the host-protective 45W antigen. Polymerase chain reaction (PCR)
      primers were designed which allowed amplification of individual family members in
      a transcript-specific manner. These were used to investigate gene expression in
      different developmental stages of the parasite by reverse-transcription
      polymerase chain reaction (RT-PCR). All members of the gene family were expressed
      during the T. ovis life-cycle. 45W gene family transcription correlates with
      embryogenesis of eggs and expression is increased in activated eggs
      (oncospheres). One family member, ToW3S, was expressed in the early larvae
      (cysticercus) stages. Expression of genes closely related to the 45W vaccine
      antigen has important implications for immune evasion under selection from the
      application of a 45W-based vaccine.

PMID- 9178270
TI  - Molecular biology of the hexokinase isoenzyme pattern that distinguishes
      pathogenic Entamoeba histolytica from nonpathogenic Entamoeba dispar.
AB  - The electrophoretic patterns of hexokinase and phosphoglucomutase have been
      widely used to distinguish Entamoeba histolytica from Entamoeba dispar isolates.
      Although E. histolytica and E. dispar, previously called pathogenic and
      nonpathogenic Entamoeba histolytica, differ clearly in sequences of many
      homologous genes, a conversion between the two has been reported by several
      laboratories, in each case showing the conversion of hexokinase (ATP, D-hexose 6
      phosphotransferase, EC 2.7.1.1) isoenzyme patterns. An apparent mobility shift of
      this enzyme may either be due to posttranslational modification or processing, or
      to the appearance of a new isoform encoded by a second gene. In this study we
      observed that the four observed bands in the isoenzyme patterns of pathogenic and
      nonpathogenic forms of Entamoeba were correlated with four different cDNAs, and
      that the four recombinant hexokinases produced in Escherichia coli comigrated
      with their natural counterparts. Polymerase chain reaction (PCR) experiments did
      not reveal hidden genes which might be responsible for conversion phenomena.
      These results strongly support the redefinition of pathogenic and nonpathogenic
      Entamoeba histolytica as two closely related species Entamoeba histolytica and
      Entamoeba dispar.

PMID- 9178271
TI  - A single locus minisatellite sequence which distinguishes between Trypanosoma
      brucei isolates.

PMID- 9178272
TI  - Effects of nifurtimox and benznidazole upon glutathione and trypanothione content
      in epimastigote, trypomastigote and amastigote forms of Trypanosoma cruzi.

PMID- 9178273
TI  - Regulated use of an alternative spliced leader exon in the plant parasitic
      nematode Meloidogyne javanica.

PMID- 9178274
TI  - A long range restriction map of chromosome 5 of Plasmodium berghei demonstrates a
      chromosome specific symmetrical subtelomeric organisation.

PMID- 9178275
TI  - Haptoglobin-related protein and apolipoprotein AI are components of the two
      trypanolytic factors in human serum.

PMID- 9178276
TI  - Molecular cloning and expression of a ribonuclease H from the kinetoplastid,
      Trypanosoma brucei.

PMID- 9178277
TI  - Golgi-associated phosphohydrolases in Trypanosoma brucei brucei.

PMID- 9178278
TI  - Six-month outcome of critically ill patients given glutamine-supplemented
      parenteral nutrition.
AB  - An abundant amino acid in the human body, glutamine (Gln) has many important
      metabolic roles that may protect or promote tissue integrity and enhance the
      immune system. Low plasma and tissue levels of Gln in the critically ill suggest
      that demand may exceed endogenous supply. A relative deficiency of Gln in such
      patients could compromise recovery and result in prolonged illness and an
      increase in late mortality. This study examines this hypothesis. Using a
      prospective, block-randomized, double-blind treatment study design, we tested
      whether a Gln-containing parenteral nutrition (PN) compared with an
      isonitrogenous, isoenergetic control feed would influence outcome, with the
      endpoints of morbidity, mortality, and cost at 6 mo postintervention. In one
      general intensive care unit (ICU), to ensure consistency of management policies,
      84 critically ill adult patients, with Acute Physiological and Chronic Health
      Evaluation II score > 10, requiring nutritional support received PN only if
      enteral nutrition was contraindicated or unsuccessful. Survival at 6 mo was
      significantly improved in those receiving Gln PN (24/42 versus 14/42; P = 0.049).
      Significantly more deaths occurred in patients requiring control PN for > 10 d (P
      = 0.03). The excess control deaths occurred later and those patients had had a
      significantly longer postintervention stay (P = 0.012) and use of ICU. In the Gln
      recipients, the total ICU and hospital cost per survivor was reduced by 50%. In
      critically ill ICU patients unable to receive enteral nutrition, a Gln-containing
      PN solution improves survival at 6 mo and reduces the hospital costs per
      survivor.

PMID- 9178279
TI  - Mononuclear blood cell magnesium content and serum magnesium concentration in
      critically ill hypomagnesemic patients after replacement therapy.
AB  - Magnesium (Mg) deficiency, commonly diagnosed as hypomagnesemia based upon low
      serum Mg concentrations, is a frequent electrolyte abnormality in critically ill
      patients. Intravenous replacement therapy is empiric and serum Mg concentrations
      have traditionally been used as guidelines for measuring efficacy. Recent studies
      have shown that the Mg content of mononuclear blood cells (MBCs) may provide a
      better index for Mg status than serum concentrations. The purpose of this study
      was to evaluate the effects of intravenous Mg replacement therapy on MBC Mg
      content and serum Mg concentrations in critically ill hypomagnesemic patients.
      Adult patients admitted to the trauma intensive-care unit (ICU) with serum Mg
      concentration < or = 0.6 mmol/L (< or = 1.5 mg/dL) were considered for study
      entry. Patients with severe renal disease (Scr > 133 mumol/L), pregnancy, or
      those who were seropositive for HIV were excluded. Ten patients with moderate (>
      0.4-0.6 mmol/L [> 1.0-1.5 mg/dL]) and severe (< or = 0.4 mmol/L [< or = 1.0
      mg/dL]) hypomagnesemia received 0.5 and 0.75 mmol/kg of intravenous MgSO4,
      respectively, over 24 h. MBC Mg content and serum concentrations of magnesium,
      phosphorus, calcium, sodium, potassium, blood urea nitrogen, creatinine, glucose,
      and albumin were measured at baseline (0 h), end of infusion (24 h), 36 h, and 48
      h. Data were analyzed using ANOVA with repeated measures and a P value < 0.05 was
      considered significant. Serum Mg concentrations increased significantly from
      baseline to 48 h (0.5 +/- 0.1 to 0.8 +/- 0.2 mmol/L, P < 0.001). MBC Mg content
      did not change significantly within the study period (2.6 +/- 1.0 to 3.0 +/- 1.3
      fmol/cell, P > 0.7). The doses of MgSO4 (0.5-0.75 mmol/kg) used in this study
      increased serum Mg concentrations, but did not result in a statistically
      significant change of MBC Mg content in this group of trauma ICU patients.

PMID- 9178280
TI  - Correlation between amino acid induced changes in energy expenditure and protein
      metabolism in humans.
AB  - The relationship between energy expenditure and protein metabolism during amino
      acid (AA) administration was evaluated in normal humans. A balanced AA solution
      was infused for 180 min at five different rates: 20 (study I), 40 (study II), 80
      (study III), 160 (study IV), and 240 mg.m2(-1).min-1 (study V), on separate days,
      in seven normal, overnight-fasted subjects (age 25 +/- 2 y; height 172 +/- 5 cm;
      weight 68 +/- 4 kg). Indirect calorimetry and [1-14C] leucine infusion techniques
      were employed. Basal total plasma AA concentration averaged 1827 +/- 121 mumol/L
      and increased to 2192 +/- 142, 2576 +/- 158, 3677 +/- 195, 5638 +/- 237, and 7185
      +/- 261 mumol/L in studies I-V, respectively. Basal energy expenditure averaged
      0.60 +/- 0.02 kcal.m2(-1).min-1 and increased slightly in studies I and II (to
      0.62 +/- 0.03, 0.63 +/- 0.02, respectively), and significantly in studies III-V
      (to 0.65 +/- 0.03, 0.70 +/- 0.04, and 0.77 +/- 0.05 kcal.m2(-1).min-1,
      respectively, all P < 0.01 versus basal; P < 0.05-0.01 for each study versus
      preceding study). Basal nonoxidative leucine disposal (NOLD), an index of protein
      synthesis, averaged 73 +/- 3 mumol.m2(-1).min-1 and increased, albeit not
      significantly, in studies I and II (to 75 +/- 5, 76 +/- 4, respectively). In
      contrast, a significant increase in NOLD was observed in studies III-V (to 87 +/-
      7, 103 +/- 7, and 127 +/- 9 mumol.m2(-1).min-1, respectively; all P < 0.01 versus
      basal; P < 0.05-0.01 for each study versus preceding study). Basal respiratory
      quotient averaged 0.81 +/- 0.02 and did not change significantly in studies I-V
      (0.80 +/- 0.02, 0.79 +/- 0.02, 0.80 +/- 0.03, 0.82 +/- 0.02 and 0.82 +/- 0.03,
      respectively). The thermic effect of AA administration, calculated as percent of
      the AA energy infused, was constant and averaged 24 +/- 4, 19 +/- 3, 17 +/- 4, 17
      +/- 3, and 18 +/- 3% in studies I-V, respectively. When AA-induced increase in
      protein synthesis was plotted with the increment in energy expenditure, a
      positive correlation was obtained (r = 0.792, P < 0.001). In summary, during AA
      administration (1) the absolute rise in energy expenditure is dose-dependent and
      does not show evidence of achieving a plateau; (2) it is positively correlated
      with AA-induced protein synthesis; and (3) the thermic effect is not dependent
      upon the AA dose administered. The data provide a quantitative assessment of AA
      induced thermogenesis in normal humans and the energy needs associated with an
      acute stimulation of protein synthesis.

PMID- 9178281
TI  - Home parenteral nutrition and vitamin B12 status.
AB  - The vitamin B12 status of 20 subjects who were on home parenteral nutrition after
      surgical or functional small bowel resection and were given 1000 micrograms
      cyanocobalamin every 3 mo was studied by comparing their plasma vitamin B12,
      homocysteine (HS), and methylmalonic acid (MMA) concentrations. The plasma
      vitamin B12 concentration (median 145 pmol/L, 95% confidence interval: 123-217)
      was subnormal in four cases and borderline in four others. In the "4low B12"
      group, the concentrations of the markers of vitamin B12 deficiency were in the
      normal range; HS 10.7 mumol/L (8.0-12.3); and MMA, 0.15 mumol/L (0.09-0.19).
      References values were HS, 10.0 mumol/L (9.4-12.6); and MMA, 0.16 mumol/L (0.10
      0.19). Thus, there were no metabolic signs of vitamin B12 deficiency in these
      subjects on parenteral nutrition, despite the fact that their plasma vitamin B12
      levels were low. Analysis of individual data showed that the four patients with
      low circulating B12 had markers of intracellular vitamin B12 deficiency in the
      normal range.

PMID- 9178282
TI  - Markers of oxidative stress in fit, health-conscious elderly people living in the
      Paris area. The Research Group on Ageing (GERBAP)
AB  - Lipid peroxidation index and antioxidant indicators were assessed by biochemical
      means in 193 healthy elderly volunteers (103 men and 90 women), ages 70-89 y and
      living freely in the Paris area. Lipid peroxidation index was in the same range
      as in young adults. Zinc, copper, and selenium levels were satisfactory and
      similar to those in young adults, though the range of copper values tended to be
      higher. Copper and selenium levels were higher in elderly women than in men.
      However, for selenium values this sex-related difference disappeared in elderly
      volunteers > 75 y. Copper-zinc-superoxide dismutase and glutathione peroxidase
      activities were similar to those in young adults, with no influence of sex or
      age. Vitamin E and total carotene, closely related to cholesterol levels, were
      satisfactory. Our findings show that markers of oxidative stress are not
      influenced by old age when good health and nutritional status are preserved, as
      in this selected population.

PMID- 9178283
TI  - Responses of plasma fibronectin to the changes of dietary protein levels in rats.
AB  - In this study, the plasma fibronectin was evaluated as a nutritional marker in
      protein- and protein-energy malnourished rats in comparison with plasma
      prealbumin, albumin, and total protein. The plasma fibronectin was determined by
      nephelometric assay based on the interaction of an antigen and antibody. The rats
      were subjected to three diets, containing 20, 5, and 0% casein, respectively, for
      5 wk except in the last 2 wk, the rats on the 0% casein diet were re-fed on a 20%
      casein diet. The results showed that in the rats on a 5% casein diet (protein
      malnourished), the plasma fibronectin concentration rose significantly in the
      early stage and normalized thereafter. In the rats subjected to a 0% casein diet
      (protein-energy malnourished), the plasma fibronectin concentration did not
      decline quickly in response to protein depletion, compared with the plasma
      prealbumin, albumin, and total protein concentrations. Following the re-feeding
      of a 20% casein diet in the last 2 wk, the plasma fibronectin concentration was
      restored earlier than other plasma protein concentrations. No significant change
      in plasma fibronectin concentration was found in the rats receiving a 20% casein
      diet (control) over the 5 wk feeding period. It is concluded that plasma
      fibronectin may not be a suitable marker for protein or protein-energy
      malnutrition, though it is a sensitive index for nutritional rehabilitation.

PMID- 9178284
TI  - Protective effects of succinic acid dimethyl ester infusion in experimental
      endotoxemia.
AB  - In rats injected with bacterial lipopolysaccharide (LPS; 5 gamma mg/g body weight
      [BWT]), the toxin provokes death within 24 h in 23% of the animals and, in
      surviving rats, causes a decrease in BWT, hyperlactacidemia, hyperlipacidemia,
      and hyperketonemia, as well as depletion of both liver and muscle glycogen
      content. In the liver, LPS severely lowers the ATP and total adenine nucleotide
      content, ATP/ADP ratio, and adenylate charge. In hepatocytes from LPS-injected
      rats, the oxidation of D-glucose is first increased 2 h after administration of
      the toxin, despite close-to-normal phosphorylation of the hexose. In hepatocytes
      prepared from rats killed 24 h after injection of LPS, the phosphorylation of D
      glucose, its incorporation into glycogen, and its oxidation are all severely
      impaired. This sequence of changes, which coincides with a decreased ratio
      between pyruvate and lactate production from exogenous D-glucose, is comparable
      to that found with agents that uncouple oxidative phosphorylation. The injection
      of LPS also alters the metabolic response of hepatocytes to the dimethyl ester of
      succinic acid (SAD), in terms, for instance, of the sparing action of the ester
      upon both the production of 14CO2 by hepatocytes prelabeled with L-[U-14C]
      glutamine and the output of NH4+, and its inhibitory action on glycogenolysis and
      futile cycling in the reactions catalyzed by glucokinase and glucose-6
      phosphatase. Nevertheless, the infusion of SAD protects the rats against the
      deleterious effect of LPS upon such variables as the plasma concentration of free
      fatty acids and beta-hydroxybutyrate, the liver ATP content, and the oxidation of
      D-glucose, as well as the pyruvate/lactate ratio, in hepatocytes prepared from
      the LPS-injected rats. The infusion of SAD also virtually suppresses lethality in
      the LPS-injected animals. It is proposed, therefore, that the infusion of
      succinic acid esters may represent a novel therapeutic approach in endotoxemia
      and multiple-organ failure.

PMID- 9178285
TI  - Iodine deficiency disorders and infertility in northeast Zaire.

PMID- 9178286
TI  - A prospective discussion of past international nutrition catastrophes-
      indications for the future.
AB  - It is of interest that, aside from starvation, the nutrition catastrophes of the
      past, including scurvy (vitamin C deficiency) resulting from lack of fresh
      vegetables and fruit and beriberi (vitamin B1 deficiency) from consumption of
      polished rice, are forgotten and only of interest as history. The problems of
      vitamins were largely considered settled by the 1950s. With the appearance on the
      market of multiple-vitamin-and-mineral tablets, the public was also satisfied and
      considered the problem of deficiencies solved. Now we are faced with unexpected
      nutrition problems primarily in the industrial West, which follow from the excess
      of dietary fats, the refining of grains to make white flour, and the alteration
      of other natural foods for general use. As we labor to understand and control
      these problems, new and unexpected "toxins," deficiencies, or excesses may
      develop. This article is a brief historical account of the past based largely on
      personal experiences and my concern for the future. The realization that the
      Western industrial world's high-fat diet was profoundly unhealthy has led to an
      attempt at correction by development of numerous low-fat foods. Unsaturated
      vegetable oils and saturated animal fats are being reduced or eliminated. In
      their place, other components and compounds are being substituted for their taste
      and consistency, without adequate concern for their nutritional value or freedom
      from toxicity. Before continuing this risk, the health of the world's population
      must be considered. Our past experiences with chemical and mechanical alteration
      of foods, and its effect on the nutrition of every man, woman, and child in the
      Western world, primarily in industrial North America, should not be forgotten.

PMID- 9178287
TI  - Indirect calorimetry in critically ill patients: clinical applications and
      practical advice.
AB  - Indirect calorimetry is the method by which metabolic rate and substrate
      utilization are estimated in human beings starting from respiratory gas exchange
      measurements and urinary nitrogen excretion. This method is based on some models
      and assumptions that must be known and taken into consideration to correctly
      interpret the results obtained. Recent advances in technology and the
      availability of precise and portable metabolic carts have made this technique
      practical at the beside even in critically ill patients. It must be considered
      that, particularly in the ICU, there may be several sources of error and many
      technical difficulties in applying this methodology. Taking into account the
      relevant clinical studies related to the outcomes of critically ill patient, this
      article defines when the assessment of energy expenditure by indirect calorimetry
      may provide useful and valid information. Review of the literature suggests that
      the clinical application of indirect calorimetry in critically ill patients,
      although promising, requires further evaluation. Currently, the potential useful
      clinical applications of indirect calorimetry in this category of patients can be
      summarized as follows: (1) assessment of energy expenditure in patients who fail
      to adequately respond to the estimated nutritional needs; (2) assessment of
      energy expenditure in patients with single- or multiple-organ dysfunction who
      need prolonged ICU care and artificial nutritional support; (3) assessment of the
      effects induced by artificial nutrition on the cardiocirculatory and respiratory
      systems in mechanically ventilated patients with acute respiratory failure; and
      (4) monitoring of VO2 during weaning from mechanical ventilation.

PMID- 9178289
TI  - The effect of a nucleotide-nucleoside solution on hepatic regeneration in rats
      after partial hepatectomy and in primary monolayer culture of hepatocytes.
AB  - Purine and pyrimidine metabolism is a key process after hepatic surgery. To
      evaluate the effect of purine and pyrimidine supplementation on hepatic
      regeneration, the following clinical in vitro and in vivo experiments were
      performed. Changes in blood nucleotides, nucleosides and nucleobase were analyzed
      by high performance liquid chromatography in patients and rats after partial
      hepatectomy. The effect of supplementation of nucleotide-nucleoside solution (OG
      VI) or their components on nucleic acids syntheses in primary monolayer cultured
      hepatocytes and preoperative intraperitoneal injection of OG-VI on hepatic
      regeneration in the partially hepatectomized rats were evaluated. Blood purine
      and pyrimidine levels in patients change after hepatectomy and their changes
      indicate increased salvage synthesis of purine and pyrimidine in the regenerating
      liver. Addition of appropriate amounts of inosine, GMP, uridine, or thymidine,
      the substrates for salvage purine and pyrimidine syntheses, to primary cultures
      of hepatocytes enhanced both DNA and RNA syntheses by the salvage and de novo
      pathways. The OG-VI mixture also enhanced the syntheses of DNA and RNA.
      Preoperative administration of OG-VI to partially-hepatectomized rats enhances
      hepatic DNA synthesis in a way similar to the in vitro study.

PMID- 9178288
TI  - The well-balanced nucleoside-nucleotide mixture "OG-VI" for special medical
      purposes.
AB  - Nucleotides and nucleosides are essential components in all cells. However,
      nucleotides have not been supplied in parenteral nutrition regimens. We developed
      a well-balanced nucleoside-nucleotide mixture "OG-VI" and examined its effect in
      animals under some stressed conditions. OG-VI was composed of 30 mmol/l of
      inosine, 30 mmol/l of guanosine monophosphate, 30 mmol/l of cytidine, 22.5 mmol/l
      of uridine and 7.4 mmol/l of thymidine. The whole body protein turnover increased
      significantly in rats receiving total parenteral nutrition (TPN) with OG-VI
      solution after 70% hepatectomy, compared with rats receiving normal TPN without
      OG-VI (122.1 +/- 20.9 mgN.kg-1.h-1 vs. 97.4 +/- 10.1 mgN.kg-1.h-1, P < 0.01, n =
      10). OG-VI significantly enhanced protein synthesis while it did not decrease
      protein breakdown. The effect of OG-VI on myocardium after hypoxic challenge was
      also examined in rats. The creatine phosphate (PCr)/inorganic phosphate (Pi) was
      decreased in normal rat myocardium after hypoxic challenge. However, in the rats
      administered OG-VI, PCr/Pi was maintained at baseline level and did not decrease
      after hypoxia. There was no significant change in the level of adenosine
      triphosphate (ATP) between before and after hypoxic challenge in myocardium of
      the rats administered OG-VI. In the rats receiving normal saline, instead of OG
      VI, the ATP level decreased significantly after hypoxic challenge (4132 +/- 276
      nmol/g tissue, n = 3, vs. 3439 +/- 465 nmol/g tissue, n = 5, P < 0.05). These
      data suggested that the well-balanced nucleoside-nucleotide mixture, OG-VI
      improved nitrogen metabolism and might stimulate synthesis of high-energy
      phosphate in recovery after severe surgical stress.

PMID- 9178290
TI  - Role of supplementation of a nucleic acid solution on the intestinal mucosa under
      total parenteral nutrition.
AB  - Since dietary nucleotides play an important role in the growth and development of
      the intestine, supplementation of a nucleic acid solution (OG-VI) may support the
      optimal growth and integrity of the intestine under total parenteral nutrition
      (TPN). Supplementation of OG-VI to a TPN solution improved mucosal morphologic
      and functional changes, increased mucosal proliferation, and decreased mucosal
      permeability of the intestine. After 80% small bowel resection, OG-VI
      supplementation to a TPN solution attenuated the initial mucosal atrophy and
      improved intestinal cell turnover. Nucleic acid supplementation may be clinically
      beneficial in certain situations.

PMID- 9178291
TI  - Role of nucleosides and nucleotides in the immune system, gut reparation after
      injury, and brain function.
AB  - Emerging evidence indicates the importance of nucleosides and nucleotides in the
      maintenance of functions of the bone marrow hematopoietic cells, intestinal
      mucosa, and the brain, which have limited de novo synthesis of purine and
      pyrimidine bases. We have found that nucleosides and nucleotides stimulate
      hemopoieses and increase peripheral neutrophil counts in mice treated with
      cyclophosphoamide. Intraperitoneal administration of nucleosides and nucleotides
      decreased bacterial translocation, the number of colony-forming units, and
      increased survival against methicillin-resistant Staphylococcus aureus. In vitro
      immune studies in mice showed that nucleosides and nucleotides increase the
      delayed-type cutaneous hypersensitivity and the popliteal lymph node blastogenic
      response to antigens, allogens, and mitogens. Both intraperitoneal and oral
      administration of nucleosides and nucleotides reduced endotoxin-induced bacterial
      translocation and improved injury to the gut in protein-deficient mice. However,
      oral administration of nucleosides and nucleotides in experimental colitis
      resulted in a worsening of colitic conditions and increased interleukin-8 and
      tumor necrosis factor-alpha concentrations in inflamed colonic portions,
      indicating the pro-inflammatory activities of nucleosides and nucleotides. Memory
      deficient senescence-accelerated mice and mice with dementia showed improved
      memory with dietary nucleosides and nucleotides supplementation. These results
      indicate that supplementation with nucleosides and nucleotides is beneficial to
      the functions of the system and the brain. However, beneficial effects to the gut
      appear to depend on the type of damage sustained by the gut.

PMID- 9178292
TI  - Glutamine saves lives! What does it mean?

PMID- 9178293
TI  - How best to determine magnesium status: a new laboratory test worth trying.

PMID- 9178294
TI  - Antioxidants in healthy elderly Parisians.

PMID- 9178295
TI  - Garlic: the key to sophisticated lowering of hepatocellular lipid.

PMID- 9178296
TI  - Influence of chronic liver disease and chronic renal failure on nutrient
      metabolism and undernutrition.

PMID- 9178297
TI  - Placenta and growth factors in fetal growth and nutrition.

PMID- 9178298
TI  - The selection of suitable substrates for hepatic energy metabolism after massive
      hepatectomy.

PMID- 9178299
TI  - Statistical issues in longitudinal studies.

PMID- 9178300
TI  - R: calcium, phosphate, and Secundum artem.

PMID- 9178301
TI  - Strategies for expanding clinical staff in an era of cost containment.

PMID- 9178302
TI  - Defining intravascular catheter-related infections: a plea for uniformity.
AB  - This article defines the complex interaction between catheterized patients and
      invading microbial pathogens. Catheter colonization reflects significant growth
      of a microbe on a catheter component. Localized intravascular catheter-related
      infection denotes infection at the exit site, tunnel tract, or pocket, in the
      absence of bloodstream infection. Systemic intravascular catheter-related
      infection is a complication of colonization or localized infection, usually
      documented by invasion of the bloodstream. Catheter sepsis is a systemic
      infection that is difficult to define because symptoms associated with
      bloodstream infection caused by the most common pathogens to infect catheterized
      patients, coagulase-negative staphylococci, may not meet the previously published
      criteria of sepsis. It is hoped that the information contained here will lead to
      greater uniformity in the definitions used by the many investigators in this
      fascinating field.

PMID- 9178303
TI  - Microbial interactions with catheter material.
AB  - The use of central venous catheters to deliver parenteral nutrition therapy is
      often complicated by infection. The original source of these infections has been
      debated but it appears that organisms colonizing the skin or those contaminating
      the catheter hub are most often responsible. Before forming a biofilm, an
      organism must first successfully attach to a surface. To do this, microbes have
      evolved strategies that allow them to adhere to surfaces and evade forces that
      would favor their detachment. Once a biofilm is formed on a catheter, the
      organisms are relatively safe from a host immune response and antibiotics. In
      this review, what is known about these interactions is discussed.

PMID- 9178304
TI  - Current laboratory techniques in the diagnosis of catheter-related infections.
AB  - The unspecificity of the clinical manifestations of catheter-related infections
      (CRIs) makes laboratory confirmation necessary, and many diagnostic techniques
      have been developed. Semiquantitative culture of catheter tips has been accepted
      by most laboratories for its simplicity and is currently the reference technique.
      It discriminates between catheters producing infection (when > or = 15 colony
      forming units grow on the culture) and insignificant colonization.
      Nonquantitative methods improve the sensitivity of diagnosis of CRI but are less
      specific. Quantitative methods improve the specificity and can identify and
      quantify colonization of both the internal and external surfaces of the catheter;
      however, these are time-consuming techniques. The high rate of unnecessary
      catheter removal has promoted interest in in situ staining methods such as gram
      staining of the skin entry site and hub. These methods are simple to perform and
      have shown a high negative predictive value. Quantitative blood culture methods
      allow the diagnosis of CRI, but their sensitivity decreases in the absence of
      associated bacteremia. Finally, the introduction of molecular techniques has
      helped to explain the pathogenesis of CRI and could help to improve the
      management of nosocomial CRI.

PMID- 9178305
TI  - Relevance of the catheter hub as a portal for microorganisms causing catheter
      related bloodstream infections.
AB  - Microorganisms causing vascular catheter-related sepsis gain access to the
      bloodstream through either the skin at the catheter insertion site or through the
      catheter hub. The catheter insertion site is probably the predominant portal for
      microorganisms in catheters in place for a short time, but the catheter hub may
      play an increasingly important role in infection in association with long-term
      catheters, particularly those that are subcutaneously tunneled. Although
      transient contamination of the catheter hub does not cause infection, certain
      microorganisms may migrate endoluminally and enter the bloodstream, causing
      bacteremia or fungemia.

PMID- 9178306
TI  - Management of catheter-related bacteremia and fungemia in patients on total
      parenteral nutrition.
AB  - To diminish the risk of serious complications from catheter-related bacteremias
      or fungemias, an optimized diagnosis and antimicrobial therapy is essential and
      early catheter removal should be considered. Prompt removal of the catheter and
      targeted antimicrobial treatment remains a common approach for febrile episodes
      in patients on total parenteral nutrition. However, novel tools allow diagnosis
      of catheter-related infections with the catheter in situ. Moreover, many of the
      established catheter-related infections caused by coagulase-negative
      staphylococci can successfully be treated with the catheter still in place. The
      use of these advanced management options depends widely on the resource of the
      microbiology laboratory as well as the type of catheter and severity of the
      patient's disease.

PMID- 9178307
TI  - Prevention of catheter-related infections: the skin.
AB  - Although intravascular devices have become indispensable tools in the care of
      seriously ill patients, the morbidity and mortality resulting from catheter
      related infections and the high cost of managing such complications may offset
      the benefits derived from these devices. A scientific understanding of the
      pathogenesis, microbiology, and risk factors involved in catheter-related
      infection is the cornerstone of any effective preventive approach. Prevention of
      vascular catheter-related infection mostly centers around inhibiting the
      adherence to the catheter of microorganisms originating from either the skin or
      the catheter hub. Two general approaches can be used nonexclusively for
      successful prevention of vascular catheter-related infection. The first approach
      does not use antimicrobial agents and includes measures such as placement and
      maintenance of vascular catheters by a skilled infusion therapy team and use of
      maximal sterile barriers. The second approach uses antimicrobial agents and
      involves the application of topical disinfectants such as chlorhexidine, use of
      silver-impregnated subcutaneous cuffs (for short-term central venous catheters),
      flushing catheters with a combination of antimicrobial and antithrombotic agents,
      and coating of catheters with either antiseptic (chlorhexidine and silver
      sulfadiazine) or antimicrobial agents (minocycline and rifampin).

PMID- 9178308
TI  - Prevention of catheter sepsis: the hub.
AB  - The prevention of catheter sepsis lies in a sound understanding of the routes
      through which catheters get contaminated. The catheter hub has been recognized as
      a portal for microorganisms causing catheter sepsis, particularly in central
      venous catheters inserted for > 1 wk. Bacteria and fungi may reach the internal
      surface of the catheter connector during manipulation by hospital staff and then
      colonize the entire lumen of the catheter. Endoluminal contamination has
      diagnostic, therapeutic, and preventive implications. Some traditional preventive
      approaches (site care, subcutaneous cuffs and tunnels, maximal aseptic barriers
      at the time of catheter insertion, and external antiseptic or antibiotic coating)
      may fail because they focus solely on the skin as a source of bacteria. Hub
      related catheter sepsis can be prevented by aseptic hub manipulation, appropriate
      junction protection, and by reducing the number of catheter lumens, side ports,
      three-way stopcocks, and changes of the infusion sets. Needleless systems must be
      evaluated in terms of their safety in preventing endoluminal contamination. A new
      disinfecting catheter hub incorporating an antiseptic barrier has been developed
      and reduced hub-related catheter sepsis by more than 90%. The endoluminal route
      of intravascular catheter contamination must be taken into account when designing
      strategies for the diagnosis and prevention of catheter-related sepsis.

PMID- 9178309
TI  - Specific problems of arterial, Swan-Ganz, and hemodialysis catheters.
AB  - In our experience, the incidence and pathogenesis of colonization may vary in
      different types of catheters. Arterial, Swan-Ganz, and hemodialysis catheters are
      good examples of this problem. This observation has implications for diagnosis,
      and the best method for each type of catheter may not be the same. In our
      opinion, laboratory diagnosis in daily practice should be limited to external
      surface cultures of the tip of intravascular catheters. Intraluminal cultures
      should be limited to research purposes, except in catheters used for parenteral
      nutrition or hemodialysis. In this case, the intradermal segment gives more
      sensitive information. Sensitivity in diagnosing pulmonary artery colonization
      can be improved by evaluating both the tip and intradermal segments. In presence
      of an indwelling introducer the intradermal segment should be replaced by the
      introducer tip.

PMID- 9178310
TI  - Endometriosis and infertility: new concepts.
AB  - Endometriosis is a common gynecological disorder with varied symptomatology
      including chronic pelvic pain, dysmenorrhea, and infertility. The association of
      endometriosis and infertility has been recognized for years, although definite
      evidence of causality still eludes us. In this review, we will explore three
      general concepts that enhance our understanding of the cellular and molecular
      interactions contributing to the pathophysiology of this disorder and that have
      steered current research in endometriosis. First, we review evidence of a local
      peritoneal inflammatory process, supported by the findings of elevated cytokine
      and growth factor concentrations in peritoneal fluid of affected patients.
      Second, we propose a role for angiogenic factors in the establishment of ectopic
      implants. Third, we review evidence for biochemical differences of eutopic and
      ectopic endometrium in endometriosis patients, which may contribute to both the
      pathogenesis and sequelae of this important disorder. Through information derived
      from these research efforts, we hope to develop better therapeutic interventions
      as adjunctive or alternative therapies to our current medical and surgical
      armamentarium.

PMID- 9178311
TI  - Severe fetomaternal hemorrhage: a review.
AB  - The etiology, clinical presentation, obstetrical antecedents, and outcome of
      pregnancies complicated by large fetomaternal hemorrhage (FMH) were reviewed by
      doing a MEDLINE search from 1966 to the present and manual search before 1966.
      One hundred thirty-four infants with FMH > 50 dl were reported in the literature.
      The primary variables: birth weight, gestational age, presence of sinusoidal
      fetal heart rate pattern, decrease or absent fetal body movements (FBM) estimated
      the amount of fetomaternal bleeding and the pretransfusion hemoglobin. Other
      variables included the condition of the infants at birth, erythroblasts, and
      reticulocyte blood counts at birth, as well as the year of publication. Thirty
      five of the 134 cases were preterm. Twenty infants born to mothers reporting
      decreased or absent FBM survived. FBM was absent in 17 cases for a period ranging
      between 24 hours and 7 days. In this group, six infants survived, five were
      stillborn, and five died in the neonatal period. A sinusoidal heart rate (SHR)
      pattern was reported in 21 cases. A SHR pattern was associated with decreased FBM
      in 13 cases (39.3 percent). Fifteen cases with sinusoidal fetal heart rate
      pattern survived (71.4 percent). Both decreased or absent FBM and SHR patterns
      were reported more often in 1990 or later than before 1990 (P < .0017 and P <
      .008, respectively). The cause of FMH was not known in 82 percent of the cases.
      The most common presenting symptoms of FMH were anemia at birth (35.2 percent),
      decreased or absent FBM (26.8 percent), and unexpected stillbirths (12.5
      percent). Seventeen intrauterine transfusions were performed in nine cases (eight
      survived). A negative correlation was found between pretransfusion hemoglobin and
      FMH (r = -0.35; P = .0019). No significant difference was found between the cases
      with FMH of > 200 ml or < 200 ml. Thus, decreased or absent FBM, SHR pattern, or
      hydrops fetalis are late signs of FMH. Other means of early detection are needed.
      The role of intrauterine transfusion (IUT) needs to be better defined. The
      inadequate outcome data indicate the need to follow infants born with large FMH
      into childhood to document the effect on the central nervous system.

PMID- 9178312
TI  - Adult respiratory distress syndrome in pregnancy: report of three cases and
      review of the literature.
AB  - Adult respiratory distress syndrome (ARDS) is rarely encountered in association
      with pregnancy, but with the decline in other causes of maternal death, is an
      increasingly important cause of mortality in obstetric patients. ARDS may result
      from a variety of different types of pulmonary injury; uniquely obstetric causes
      include preeclampsia, amnionitis-endometritis, obstetric hemorrhage, and
      tocolytic therapy. Crucial management issues include support of maternal
      oxygenation and cardiac output, myriad interactions between the pulmonary process
      and its treatment, with maternal and fetal physiology, and decision making
      regarding delivery. Our review of the literature suggests that, for the patient
      requiring antepartum intubation for ARDS, except at a very early gestational age
      or when pyelonephritis or varicella pneumonia is a cause of respiratory
      compromise, delivery will likely be required for maternal and/or fetal
      indications, and an early decision for delivery may be beneficial. Postpartum
      management is similar to treatment of the nonpregnant patient with ARDS, with
      aggressive attention to potential surgically correctable causes for infection.
      Maternal mortality rates are affected little by duration of intubation, and
      therefore prolonged mechanical ventilation is justified and appropriate for
      mothers with ARDS.

PMID- 9178313
TI  - Urinary beta-core hCG: screening for aneuploidies in early pregnancy (11-14
      weeks' gestation).
AB  - Initial studies at 17-22 weeks' gestation evaluating urinary beta-core human
      chorionic gonadotrophin (hCG) as a marker for Down's syndrome had suggested that
      it may have more potential than its serum counterpart. This study measured
      maternal urinary beta-core-hCG and creatinine at 11-14 weeks' gestation in a
      series of 26 aneuploidies (nine trisomy 21, five trisomy 18, four 45,X0, and
      eight others). The normal range for beta-core-hCG and beta-core-hCG/ creatinine
      was derived from 198 normal singleton pregnancies. Trisomy 18 cases (n = 5) had
      low maternal urinary beta-core-hCG creatinine levels (median 0.35 MOM, range 0.08
      0.82 MOM). Whereas the other aneuploidies had no particular pattern; in
      particular, the trisomy 21 cases (n = 9) (median 1.16 MOM, range 0.3-4.74 MOM)
      did not differ significantly from 1 MOM. The findings imply that maternal urinary
      beta-core-hCG is not as discriminating for Down's syndrome between 11 and 14
      weeks as later on in pregnancy.

PMID- 9178314
TI  - Screening for Down syndrome pregnancy using beta-core fragment: prospective
      study.
AB  - Two recent publications by Cuckle et al., and one each by Canick et al. and
      Kellner et al., describe the use of urine beta-core fragment measurements as a
      screening test for Down syndrome pregnancies. Median levels of over 5.4 MOM were
      reported for cases of Down syndrome, with an over 72 per cent detection rate for
      a 5 per cent false-positive rate. Urine beta-core fragment was suggested as a
      superior screening test for Down syndrome pregnancies. These four studies were
      retrospectives, with samples from affected cases collected at different sites
      from those from normal cases. In the present study, prospective data were
      collected for 726 pregnancies over a 9-month period at a single medical centre.
      Fresh samples were assayed continuously, without knowledge of the karyotype.
      Urinary beta-core fragment levels in 709 unaffected samples continually declined
      from 12 to 24 weeks of pregnancy. A logarithmic fit was optimal for the median
      curve. The log standard deviation of unaffected samples was 0.368. All 13 Down
      syndrome cases had levels exceeding 1.0 MOM, with a median value of 4.1 MOM.
      Eight of 13 Down syndrome cases (62 per cent) had levels exceeding the 95th
      centile. Results have not been adjusted for maternal age, which may improve the
      detection rate. The results reported here, while less impressive than those
      reported previously, confirm the usefulness of urine beta-core fragment as a
      screening test for Down syndrome. Because of the prospective nature of this
      study, the 62 per cent sensitivity suggested here might be more representative of
      the true performance of urinary beta-core fragment in clinical practice than the
      higher rates observed in previous studies. Results for this single urine test are
      similar to those for triple screen and other serum combination tests. Single
      analyte urine beta-core fragment tests, or beta-core fragment combination
      protocols, may eventually replace serum analytes in screening for Down syndrome
      pregnancies.

PMID- 9178315
TI  - Fetal biometric ratios by transvaginal sonography as a marker for aneuploidies in
      early pregnancy.
AB  - The aim of this study was to obtain by transvaginal sonography in early pregnancy
      normal biometric charts of some fetal ratios and to evaluate the utility of these
      ultrasonographic indices as biometric markers for the identification of fetal
      chromosome abnormalities. The study population included 1054 normal euploid
      fetuses and 30 fetuses with an abnormal karyotype. We obtained six standard
      ultrasound measurements by transvaginal sonography at 11-16 weeks' gestation
      before genetic amniocentesis in patients at risk for genetic disorders. Seven
      biometric ratios (biparietal diameter/femur length, biparietal diameter/humerus
      length, head circumference/abdominal circumference, abdominal circumference/femur
      length, abdominal circumference/humerus length, femur length/foot length, and
      humerus length/foot length) were calculated and reference curves were plotted.
      The ratios from aneuploid fetuses showed no differences from reference ranges.
      Only in trisomy 13 fetuses were abnormal values of head circumference/abdominal
      circumference, biparietal diameter/humerus length, and biparietal diameter/femur
      length ratios detected, probably due to the high incidence of microcephaly and
      central nervous system malformations in these fetuses. The normal values of
      sonographic ratios obtained by transvaginal sonography in the first and early
      second trimester of pregnancy cannot generally be considered a useful tool for
      the detection of chromosomal abnormalities. Only ratios involving cephalic
      measurements can be used in early pregnancy as screening markers in the detection
      of trisomy 13 fetuses.

PMID- 9178316
TI  - Acceptance of first-trimester prenatal diagnosis for the haemoglobinopathies in
      Lebanon.
AB  - We have interviewed 83 couples at risk for a haemoglobin disorder, mostly beta
      thalassaemia, in an effort to evaluate their attitude towards first-trimester
      prenatal diagnosis. Most of the families had received poor education and were of
      low socio-economic status and more than half of the couples were not properly
      aware of their genetic risk. Fifty-nine per cent of the couples were definitely
      in favour of prenatal diagnosis, 23 per cent were uncertain at the time of the
      interview, and 18 per cent were opposed to such testing, because of their
      religious conviction against termination of a pregnancy. Another important factor
      which seems to influence choice was the cost of the test. Essential issues that
      arise from this study include the importance of a control programme adapted to
      particular populations, proper information and counselling, and the need for
      financial support in countries such as Lebanon.

PMID- 9178317
TI  - Microsatellite markers in the indirect analysis of the steroid 21-hydroxylase
      gene.
AB  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia due to steroid
      21-hydroxylase (21-OH) deficiency has been proved to be effective. Screening for
      a panel of nine point mutations, deletions, and gene conversions allows the
      identification of most of the mutations, although 6.12 per cent of chromosomes
      remain uncharacterized. In the present study, microsatellite typing in the HLA
      region was performed in 23 21-OH deficiency families to determine the usefulness
      of these markers in the indirect identification of disease alleles. Two Genethon
      markers (D6S273 and D6S439) in the HLA complex, class III and II regions in 5'
      and 3', respectively to the CYP21 gene, were typed together with a microsatellite
      at intron 3 of the TAP1 gene also in 3'. The heterozygosity of these markers
      provided informativity in all but on family, in which only the father was
      informative. Direct genotyping of the chromosomes confirmed in each case the
      correct assignment of the disease alleles in the sibling. The indirect analysis
      of the 21-OH gene through D6S273, TAP1, and D6S439 microsatellites provides
      useful information in the molecular analysis of steroid 21-OH deficiency.

PMID- 9178318
TI  - Prenatal diagnosis of steroid 21-hydroxylase deficiency by analysis of polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP) profiles.
AB  - The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      profile analysis could be applied to the prenatal diagnosis of steroid 21
      hydroxylase deficiency. We designed PCR primers to amplify most of the 21
      hydroxylase gene, including all the mutations previously reported. PCR-SSCP
      analysis in eight patients showed at least one polymorphic site in each case. We
      confirmed that the mobility shifts in SSCP in an affected kindred were
      transmitted as a Mendelian trait. As these results indicated that PCR-SSCP
      profiles could be used for DNA-based diagnosis, we attempted to use this
      technique for prenatal diagnosis. DNA was obtained by chorionic villus sampling
      of a fetus and PCR-SSCP profiles were analysed in the PCR-amplified fragments in
      which the mobility shifts had been observed in the SSCP of the proband. We
      concluded that the fetus was a carrier. Direct nucleotide sequencing and allele
      specific oligonucleotide hybridization confirmed that the fetus was heterozygous.
      At birth, the infant showed no signs of virilization or of abnormal endocrine
      findings on laboratory study. The results suggest that this new application of
      PCR-SSCP has advantages over conventional RFLP analysis and is useful in making a
      prenatal diagnosis of steroid 21-hydroxylase deficiency both rapidly and
      accurately.

PMID- 9178319
TI  - Maternal uniparental disomy of chromosome 2 and confined placental mosaicism for
      trisomy 2 in a fetus with intrauterine growth restriction, hypospadias, and
      oligohydramnios.
AB  - We present a case of maternal uniparental heterodisomy for chromosome 2 (UPD 2)
      detected after trisomy 2 mosaicism was found on placental biopsy. This case
      presented prenatally with severe intrauterine growth restriction (IUGR) and
      oligohydramnios. The diploid newborn had hypospadias and features consistent with
      oligohydramnios sequence. He died shortly after birth of severe pulmonary
      hypoplasia. The term placenta had high levels of trisomy 2 in both the
      trophoblast and the stroma. A comparison of this case with others reported in the
      literature suggests that the IUGR and oligohydramnios are likely related to
      placental insufficiency due to the high levels of trisomy 2 present in the
      trophoblast of the term placenta and the presence of UPD 2 in the diploid
      placental line.

PMID- 9178320
TI  - Fetal pyelectasis: comparison of postnatal renal pathology with unilateral and
      bilateral pyelectasis.
AB  - The aim of this study was to determine the prenatal fetal pyelectasis which
      requires postnatal evaluation. This was a retrospective analysis involving 65
      infants with complete urological follow-up; 59 had shown prenatal evidence of
      pyelectasis using previously published standards. Males were more common in both
      the normal (75 per cent) and the abnormal (77 per cent) postnatal outcome groups.
      Unilateral prenatal lesions were less common than bilateral, but had significant
      postnatal pathology in 47 and 26 per cent, respectively (n.s.). Persistent
      dilatation was likely to be associated with postnatal pathology. A 6 mm threshold
      of dilatation predicted the 19 infants with significant postnatal pathology. The
      majority of fetuses with pyelectasis in the study had normal outcomes, with males
      often showing 'transitory pyelectasis'. A repeat prenatal scan at 30-40 weeks'
      gestation is recommended for all fetuses where 6 mm or more of renal pelvic
      dilatation is detected prior to 28 weeks. Postnatal follow-up is required for
      persistent pyelectasis.

PMID- 9178321
TI  - Caution: prenatal clubfoot can be both a transient and a late-onset phenomenon.
AB  - Clubfoot (talipes equinovarus) is a common orthopaedic malformation that can be
      accurately diagnosed prenatally. The study was conducted to investigate possible
      in utero visualization of transient and late-onset clubfoot. Early (13-16 weeks'
      gestation) prenatal transvaginal sonographic diagnosis of clubfoot deformity was
      made in 36 cases during the study period. Only those cases where follow-up
      examination revealed different sonographic findings were considered. The results
      showed that seven cases of transient (as well as relapsing) clubfoot were
      identified. In 4 of 7 cases, the clubfoot resolved (all after more than 10 min of
      observation) during the same examination. In the fifth and sixth cases, it
      initially resolved, later reappearing in follow-up examinations (20 and 22 weeks'
      gestation). In the seventh case, the clubfoot persisted for two consecutive
      examinations (2 weeks apart each) and later disappeared. In addition, six late
      onset (22-24 weeks' gestation) clubfoot cases were identified during the study
      period. Although infrequent, in utero clubfoot can be both a transient and a late
      onset phenomenon. Over- and under-diagnosis are potential hazards in these
      situations.

PMID- 9178322
TI  - Ultrasonography of fetal heart failure in early gestation.
AB  - Cardiac dysfunction was observed with transvaginal ultrasound in 12 fetuses at 13
      17 weeks' gestation. Impaired contractility of the heart and significant
      reduction of the left ventricular fractional shortening were noted in these
      fetuses. Three of the fetuses also had supraventricular tachycardia. Many of the
      fetuses had cardiomegaly, oligohydramnios, a thick placenta, or associated
      cardiac and structural anomalies.

PMID- 9178323
TI  - Resolution of hydrops in twin-twin transfusion syndrome: could steroids have a
      role?
AB  - A case of twin-twin transfusion is presented with hydrops occurring twice in the
      recipient twin and resolving. Polyhydramnios was treated with numerous volume
      reducing amniocenteses (amnioreductions), which were performed prior to both
      occurrences of hydrops. Amnioreductions were only performed before the first
      resolution of hydrops, whereas betamethasone was given prior to both episodes of
      hydrops resolving. Steroids may be useful not just in case of premature delivery
      but also to help a compromised fetus cope in utero.

PMID- 9178324
TI  - Concordant anencephaly in monoamniotic twins and an analysis of maternal serum
      markers.
AB  - Anomalies occur with greater frequency in twin gestations than in singleton
      pregnancies. Anencephaly is not an uncommon defect, but because of its
      multifactorial inheritance pattern, twins are usually discordant for this
      anomaly. We present a case of monoamniotic twins concordant for anencephaly.
      Monoamniotic anencephalic twins were diagnosed at 15 weeks' gestation. Normal
      interval growth occurred until intrauterine demise of both fetuses at 28 weeks.
      Maternal serum obtained at 16.5 weeks demonstrated low unconjugated oestriol
      (uE3) levels and elevated values of alpha-fetoprotein, although this result was
      lower than expected. Human chorionic gonadotropin (hCG) levels were significantly
      elevated. Monoamniotic twins concordant for anencephaly occur with extreme
      rarity. To our knowledge, maternal serum uE3 and hCG levels in fetuses concordant
      for neural tube defects have not been previously reported.

PMID- 9178325
TI  - Prenatal diagnosis of a tetraploid fetus.
AB  - A tetraploid fetus with an unusual facial appearance and multiple congenital
      anomalies (large cerebral lateral ventricles; lung, cardiac, and genital
      abnormalities) is reported. Chromosome analysis was performed on amniocytes and
      fetal blood lymphocytes. A comparison is made with other reported cases (nine
      liveborn infants and one 17.2-week-old fetus).

PMID- 9178326
TI  - Prenatal ultrasound diagnosis of abdominal aortic aneurysm with fibrotic
      occlusion in aortic branch vessels.
AB  - In a 35-year-old multiparous patient, an ultrasound scan performed at 32 weeks'
      gestational age for size less than dates revealed an appropriately grown fetus
      with a two-vessel umbilical cord. Also noted were dilated, tortuous abdominal and
      pelvic vessels. A scan at 33.5 weeks confirmed the two-vessel cord and noted a
      widely dilated abdominal aorta and a left foot 2 cm shorter than the right.
      Delivery at 36 weeks was followed by a neonatal course complicated by thromboses,
      renovascular hypertension, and a newly patent ductus with pulmonary hypertension.
      Successful ligation was followed by acute pulmonary hypertension, cardiac
      dysfunction and death. Autopsy findings included aneurysmal dilation of the
      abdominal aorta without evidence of arterial wall pathology.

PMID- 9178327
TI  - Prenatal diagnosis of lamellar ichthyosis by direct mutational analysis of the
      keratinocyte transglutaminase gene.
AB  - Autosomal recessive lamellar ichthyosis (LI) is a rare inherited disease of
      cornification of the skin. Recently, the gene responsible for type I LI has been
      identified and mutations have been described. The identification of mutations in
      families at risk for LI allows a precise and rapid prenatal diagnosis. A family
      with a previously unreported mutation is described and a prenatal diagnosis based
      on a simple polymerase chain reaction (PCR) approach is outlined. The molecular
      diagnosis was confirmed on post-mortem examination of the skin.

PMID- 9178328
TI  - Cross-hybridization of the chromosome 13/21 alpha satellite DNA to chromosome 22
      or a rare polymorphism?

PMID- 9178329
TI  - Re: Second-trimester maternal serum alpha-fetoprotein, human chorionic
      gonadotropin, and unconjugated oestriol after early transvaginal multifetal
      pregnancy reduction.

PMID- 9178330
TI  - Current awareness in prenatal diagnosis.

PMID- 9178331
TI  - Sociality and immunological health revisited.

PMID- 9178332
TI  - Psychophysiological assessment of respiratory function in panic disorder:
      evidence for a hyperventilation subtype.
AB  - OBJECTIVE: Previous research has found differences in respiratory function
      between panic disorder and other anxiety disorder populations. These differences
      have been explained as reflecting either a) a specific feature of panic disorder,
      b) merely a sign of increased general arousal, or c) a result of population
      sampling error. The current study addressed the question of such differences by
      using improved methodology over previous research. A preliminary evaluation of
      respiratory symptoms during panic attacks was undertaken as a means of
      identifying a respiratory-sensitive subtype of the panic patient. METHOD:
      Seventeen panic disorder patients (PD), 18 patients with generalized anxiety
      disorder (GAD), and 20 normal control (NC) subjects were administered a
      psychophysiological evaluation composed of baseline, stressor, and recovery
      phases. Panic patients were measured for the severity of respiratory symptoms
      during panic attacks. End-tidal CO2 (EtCO2) and respiration rate were measured
      throughout the psychophysiological evaluation. RESULTS: PDs demonstrated
      significantly lower baseline EtCO2 levels than the GADs and NCs, in spite of
      being equivalent to GADs on baseline anxiety levels. Moreover, panic patients
      reporting a high level of respiratory symptoms during panic attacks seemed to
      account for the bulk of observed differences. CONCLUSIONS: These findings lend
      support to a group of studies showing differences in respiratory function between
      panic disorder and other anxiety disorder populations. In addition, this study
      provides preliminary support for the presence of a distinct "hyperventilation
      subtype" of panic disorder. The implications of these findings for future
      research and treatment are discussed.

PMID- 9178333
TI  - Heart rate variability in patients with coronary artery disease: differences in
      patients with higher and lower depression scores.
AB  - OBJECTIVE: This study tested the hypothesis that coronary artery disease patients
      with higher depression scores have lower heart rate variability during daily
      life. METHOD: Thirty-three men and nine women, ranging in age from 46 to 79, with
      coronary artery disease and exercise-induced ischemia were studied. The standard
      deviation of normal R-R intervals (SDNN) and average heart rate were obtained
      from 24-hour ambulatory electrocardiographic monitoring. Patients were grouped by
      a median split of the Minnesota Multiphasic Personality Inventory (MMPI-D) score.
      RESULTS: SDNN was lower (p = .009) and average heart rate was higher (p = .003)
      in patients with higher depression scores. These relationships remained
      substantially unaltered after statistically adjusting for the only
      demographic/clinical factor that varied between the groups: gender. CONCLUSIONS:
      In comparison to the lower depression score group, those with higher depression
      scores had lower heart rate variability during daily life. These findings may be
      related to the reported relationship between depression and survival risk in
      patients with coronary artery disease.

PMID- 9178334
TI  - Laterality in somatization.
AB  - OBJECTIVE: To identify whether there is a lateralized pattern in somatic symptoms
      related to emotional disturbances. METHOD: Sixty-one patients with depressive
      disorders, anxiety disorders, and somatization disorders were examined for the
      lateralized distribution of somatic symptoms in the body and its relationship to
      the severity of anxiety and depression. RESULTS: The chief somatic symptoms
      presented significantly more on the left side than on the right side of the body.
      Headache and other forms of pain, especially, occurred more on the left side.
      There was no significant difference between left-sided and right-sided groups in
      demographic variables such as age, gender, marital status, education level,
      diagnosis, and duration of illness. The scores on Hamilton's anxiety scale or
      Hamilton's depression scale were higher in the left-sided group than the right
      sided group, although the difference was not statistically significant.
      CONCLUSIONS: These results suggest that the right hemisphere of the brain is more
      involved then the left with somatization symptom formation related to emotional
      disturbances.

PMID- 9178335
TI  - Effects of nortriptyline on depression and glycemic control in diabetes: results
      of a double-blind, placebo-controlled trial.
AB  - OBJECTIVE: Depression is a prevalent and chronic condition in diabetes and is
      associated with poor glucose regulation and poor compliance with diabetes
      treatment. This investigation evaluated the effects of nortriptyline on
      depression and glycemic control to see whether depression in diabetes is
      treatable and whether restoring mental health contributes to improved medical
      outcome. METHOD: Sixty-eight diabetic patients with poor glycemic control, 28 of
      whom had active major depression (DSM-IIIR), completed a randomized, placebo
      controlled, double-blind trial involving 8 weeks of treatment with nortriptyline
      targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was
      determined with the Beck Depression Inventory; glucose control was measured by
      glycated hemoglobin levels. Compliance behavior was assessed using medication
      dispensing devices and glucometers equipped with electronic memory. RESULTS: The
      reduction in depression symptoms was significantly greater in depressed patients
      treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8,
      p = .03). Nortriptyline was not statistically superior to placebo in reducing
      glycated hemoglobin of the depressed subjects (p = .5). However, path analysis
      indicated that the direct effect of nortriptyline was to worsen glycemic control
      whereas depression improvement had an independent beneficial effect on glycated
      hemoglobin. These findings were not explained by the relationships of
      nortriptyline treatment to weight change (r = -0.21, p = .31) or depression
      improvement to compliance with the protocol for self-monitoring of blood glucose
      (r = 0.01, p = .97). CONCLUSIONS: Major depression in diabetic patients can be
      effectively treated with nortriptyline at the expense of a direct hyperglycemic
      effect. Path analysis demonstrated a treatment-independent effect of depression
      improvement on glycemic control, suggesting that a more ideal antidepressant
      agent may both restore mental health and improve medical outcome.

PMID- 9178336
TI  - Plasma catecholamine and lymphocyte beta 2-adrenergic receptor alterations in
      elderly Alzheimer caregivers under stress.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of chronic
      stress on beta-adrenergic physiology in elderly spousal caregivers to Alzheimer
      patients. METHODS: Thirty-seven elderly spousal caregivers and matched
      noncaregiver controls (mean age 73 years, SD = 6) were studied. Life stress
      categorization (presence of marked threat) covering the previous 6 months was
      determined using a semistructured interview based on the Psychiatric
      Epidemiological Research Inventory and the Life Events and Difficulties Schedule.
      beta 2-adrenergic receptor sensitivity (isoproterenol-stimulated cyclic AMP
      accumulation) and density were determined in lymphocytes. RESULTS: Caregivers
      with high life stress had higher plasma norepinephrine levels (p < .04) but no
      change in plasma cortisol. For beta-receptor sensitivity, 30% of the variance was
      accounted for by high life stress rating, increased age, being male, and lower
      norepinephrine (p = .018); 17% of the variance in beta-receptor density was
      accounted for by plasma norepinephrine (p = .03). CONCLUSIONS: The findings
      demonstrate that chronic high stress may be associated with changes in adrenergic
      physiology and may provide a mechanism through which chronic stress alters
      cellular immunity.

PMID- 9178337
TI  - Prediction of quality of life after coronary artery bypass graft surgery: a
      review and evaluation of multiple, recent studies.
AB  - OBJECTIVE: To review studies predicting psychosocial outcome after coronary
      artery bypass graft surgery (CABG). METHODS: Seventeen prospective studies,
      appearing in the MEDLINE and PsycLIT data bases between 1986 and 1996, were
      reviewed regarding objectives, methodological issues, results, and clinical
      relevance. RESULTS: All studies reported that psychological factors bad
      predictive value. In particular, preoperative anxiety and depression predicted
      postoperative psychological maladjustment; social support, preoperative feelings
      of control, denial, and optimism contributed to psychological adjustment.
      CONCLUSIONS: Many specific psychological outcomes seem to be best predicted by
      preoperative assessment of functions in that specific area, especially in the
      case of anxiety and depression. Furthermore, personality factors including
      denial, optimism, control, and the need for support appear to be predictors of
      psychological outcome. Appropriate identification of predictive factors might
      improve the development of individually tailored interventions for patients at
      risk of postoperative psychological problems.

PMID- 9178338
TI  - Openness to discuss cancer in the nuclear family: scale, development, and
      validation.
AB  - OBJECTIVE: To describe the development and validation of a scale for assessing
      openness to discuss cancer in the family. METHOD: Two studies were conducted.
      Study 1 was a cross-sectional study designed to test the factor structure of the
      scale. Four hundred ninety-eight patients with either breast cancer or Hodgkin's
      disease were interviewed. In Study 2, a longitudinal study, 133 patients with
      cancer in the head and neck were tested at four points in time: just before
      treatment, 6 weeks, 13 weeks and 52 weeks after treatment. Study 2 aimed to
      confirm the factor structure established in Study 1, to test for construct
      validity in a new population, to test the psychometric properties of the Openness
      Scale, and to test the scale's sensitivity to change. RESULTS: In Study 1, a one
      factor solution was revealed, resulting in a scale of eight items. In Study 2,
      the factor structure found in Study 1 was confirmed. In line with theoretical
      expectations, subjects who perceived their communication about cancer as more
      open showed more positive rehabilitation outcomes especially at 13 weeks after
      treatment (less uncertainty, fewer negative feelings, more control, higher self
      esteem, fewer psychological and physical complaints). Furthermore, more open
      communication related with more support by family members and more discussion
      with the partner. The scale was found to be stable over time. CONCLUSIONS: The
      scale's construction and subsequent analysis show that open discussion of
      problems (related to cancer) in the family can be measured reliably with an eight
      item instrument. Additional validation of the scale is indicated.

PMID- 9178339
TI  - Psychological sequelae of cancer diagnosis: a meta-analytical review of 58
      studies after 1980.
AB  - OBJECTIVE: In a review of the literature from 1980 to 1994 on psychological and
      psychiatric problems in patients with cancer, the prevalence, severity, and the
      course of these problems (i.e., depression, anxiety, and general psychological
      distress) were studied with the help of meta-analyses and qualitative analyses.
      Apart from this, qualitative analyses were also applied with respect to other
      relevant variables. METHOD: A literature search in MEDLINE was conducted and
      cross-references of articles identified via MEDLINE. Meta-analysis was applied
      when possible. RESULTS: There seemed to be a wide variation across studies in
      psychological and psychiatric problems. Meta-analysis showed no significant
      differences between cancer patients and the normal population with respect to
      anxiety and psychological distress. However, cancer patients seemed to be
      significantly more depressed than normals. Compared with psychiatric patients,
      cancer patients were significantly less depressed, anxious, or distressed.
      Compared with a sample of other medical patients, cancer patients showed
      significantly less anxiety. With respect to course, a significant decrease was
      found in the meta-analysis for anxiety, but not for depression. Further meta
      analyses showed significant differences among groups of cancer patients with
      regard to tumor site, sex, age, design of the study, and year of publication.
      From the qualitative analyses, it seemed that medical, sociodemographic, and
      psychological variables were related inconsistently to psychological and
      psychiatric problems. CONCLUSION: With the exception of depression, the amount of
      psychological and psychiatric problems in patients with cancer does not differ
      from the normal population. The amount of psychological and psychiatric problems
      is significantly less in cancer patients than in psychiatric patients. The amount
      of anxiety is significantly less in cancer patients than in other groups of
      medical patients with mixed diagnoses, whereas depression is not. Future studies
      should aim at exploring possible causes for the sometimes impressive differences
      in psychological or psychiatric problems among patients with cancer.

PMID- 9178341
TI  - Cynical hostility, powerful others control expectancies, and patient adherence in
      hemodialysis.
AB  - OBJECTIVE: The present study examined the joint role of cynical hostility and
      powerful others health locus of control expectancies in predicting regimen
      adherence in a sample of center hemodialysis patients. METHOD: Forty-eight
      hemodialysis patients completed the Cook-Medley Hostility (Ho) Scale and the
      Powerful Others Health Locus of Control (PHLC) scale. Adherence to the fluid
      restriction and phosphorus reduction components of the treatment regimen was
      assessed by examining patients' interdialysis session weight gains and serum
      phosphorus (P) levels. RESULTS: In a hierarchical regression analysis, higher
      hostility was associated with significantly higher serum P levels indicating
      poorer dietary and medication adherence. The main effect for hostility was
      qualified by the interaction of hostility and PHLC. This pattern indicated that
      the deleterious effect of hostility on adherence was most pronounced among
      patients possessing the expectancy that positive health outcomes are not strongly
      contingent on the actions or advice of powerful others (eg. health care
      providers). Similar analyses failed to show significant effects for hostility or
      PHLC in the prediction of interdialytic weight gain. CONCLUSIONS: The present
      findings suggest that jointly assessing hostility and health-related expectancies
      may be useful in identifying chronically ill patients who are potentially at risk
      for difficulties in performing a prescribed regimen.

PMID- 9178340
TI  - Smoking status and nicotine administration differentially modify hemodynamic
      stress reactivity in men and women.
AB  - OBJECTIVES: To investigate the impact of cigarette smoking and oral contraceptive
      (OC) use on hemodynamic stress responses of women. Also, to examine gender
      differences in stress reactivity as a function of smoking status and acute
      nicotine administration. METHODS: Thirty men and 46 women, differing in smoking
      status and OC use, were tested for cardiovascular stress responses to a variety
      of behavioral and physical stressors. Each was tested twice, once under a
      transdermal nicotine patch condition and once under a placebo patch condition.
      Impedance cardiography was used to estimate hemodynamic reactivity noninvasively.
      RESULTS: In response to behavioral stressors, women smokers, irrespective of OC
      use or nicotine vs placebo, demonstrated significantly blunted cardiac output and
      heart rate reactivity to stressors, and showed significantly greater estimated
      total peripheral resistance (TPR) under stress relative to women nonsmokers.
      There were no differences in hemodynamic stress reactivity between men smokers
      and nonsmokers. The only significant effect involving nicotine administration on
      stress reactivity was seen in men where, regardless of smoking status, nicotine
      increased heart rate reactivity to all stressors relative to placebo responses.
      CONCLUSIONS: Results suggest that cigarette smoking may act differently in men
      and women to increase risk for cardiovascular disease (CVD). For men, nicotine
      may exert pathogenic influences via increasing the magnitude of heart rate
      reactivity to stressors. For women, however, smoking seems to have deleterious
      effects on hemodynamic stress reactivity patterns, reducing myocardial but
      increasing TPR contributions to blood pressure responses.

PMID- 9178342
TI  - Treating myopia with acoustic biofeedback: a prospective study on the evolution
      of visual acuity and psychological distress.
AB  - OBJECTIVE: The effects of a visual training technique on changes in myopia,
      visual acuity, and psychological distress were studied in a controlled
      prospective study. METHOD: A group of 33 female students with myopia < or = 3.50
      diopters (D) underwent visual training using an acoustic biofeedback technique. A
      group of 22 female students with myopia and a group of 27 students with
      emmetropia formed the two control groups, matched for school, age, sex, and
      refractive error. Manifest and cycloplegic refraction, visual acuity, personality
      profile (CPI), and psychological distress (SCL-90) were measured at the baseline
      (T0), at 10 weeks (T1), and after 12 months (T2). RESULTS: At T2, myopia
      significantly progressed both in the treated and in the untreated students with
      myopia. Visual acuity improved only in the treated myopia group (despite
      refraction objectively being worse). No differences were found among the
      personality profiles in the three groups. All items indicative of psychological
      suffering improved in the group treated for myopia whose visual acuity was
      ameliorated. CONCLUSIONS: The visual training technique led to no improvement in
      objective measures of visual acuity, but did lead to an improvement in one
      relatively subjective measure of visual acuity and a parallel improvement in
      psychological conditions. The students with myopia who were treated consequently
      had a greater sense of general well-being.

PMID- 9178343
TI  - Experimenter expectancy in resistance to respiratory air flow.
AB  - OBJECTIVE: The effect of experimenter expectancy was investigated on the
      resistance to respiratory air flow, measured as total respiratory resistance (Rt)
      in healthy individuals. METHOD: Each of three naive experimental assistants
      collected air flow resistance responses from 30 subjects who they had been told
      were either likely or unlikely to respond to the suggestion of breathing
      difficulty. RESULTS: The subjects were assigned to the two conditions at random.
      The subjects who were described to the experimenters as being likely to respond
      exhibited greater Rt increases to bronchoconstriction suggestion than did the
      subjects who were described as unlikely to respond. CONCLUSIONS: These findings
      confirmed the presence of a source of variance that has not been considered
      previously in suggestion studies.

PMID- 9178344
TI  - Surface dependence: a balance control strategy in panic disorder with
      agoraphobia.
AB  - OBJECTIVE: Previous studies have reported vestibular dysfunction and impaired
      balance in patients with agoraphobia. Vestibular dysfunction may lead to an
      information processing strategy focusing on spatial stimuli from two
      nonvestibular sensory channels, vision and proprioception. This nonvestibular
      balance control strategy may in turn lead to discomfort in situations involving
      inadequate visual or proprioceptive spatial cues (space and motion discomfort).
      The objective of this study was to examine sensory integration of spatial
      information in agoraphobia. Because of previous findings that space and motion
      discomfort and vestibular dysfunction are common in agoraphobia, we hypothesized
      that agoraphobics would use a nonvestibular balance control strategy. METHOD:
      Using computerized dynamic posturography, we examined balance performance in
      patients with panic disorder with agoraphobia, uncomplicated panic disorder,
      nonpanic anxiety disorders, and depression without anxiety, as well as healthy
      subjects for comparison. The posturography procedure included six sensory
      conditions in which visual and proprioceptive balance information was manipulated
      experimentally by permutations of sway-referencing the support surface or the
      visual surround or by having patients close their eyes. RESULTS: The agoraphobics
      had impaired balance when proprioceptive balance information was minimized by
      sway-referencing the support surface (p < 0.02). This pattern, called surface
      dependence, tended to be more pronounced in agoraphobics who reported space and
      motion discomfort, including fear of heights or boats. CONCLUSION: Agoraphobics
      rely on proprioceptive cues for maintenance of upright balance. This strategy may
      lead to intolerance of situations characterized by unstable support.

PMID- 9178345
TI  - Clinical effects of blood pressure biofeedback treatment on hypertension by auto
      shaping.
AB  - OBJECTIVE: Although biofeedback has been reported to be efficacious in the
      treatment of hypertension, the degree of response has varied. This study
      investigated the mechanisms of blood pressure reduction by biofeedback. METHOD:
      Thirty outpatients with essential hypertension (10 men and 20 women) aged 38 to
      65 years were studied. Subjects were randomly assigned to group A or B. Subjects
      in group A underwent biofeedback treatment once a week for a total of four
      sessions. Those in group B self-monitored their blood pressure during the
      sessions as the control period and later underwent the same biofeedback
      treatment. RESULTS: Blood pressure measured by doctor was reduced by 17 +/- 18/8
      +/- 7 (p < .01) and elevation of pressure induced by mental stress testing was
      suppressed by 8 +/- 9 (p < .05)/4 +/- 8 during the treatment period in group A
      (mm Hg). In group B, both blood pressure measured by doctor and elevation of
      pressure by mental stress testing remained unchanged during the control period
      and they were later suppressed by 20 +/- 15/9 +/- 7 (p < .01) and 11 +/- 10(p <
      .05)/5 +/- 9 by the biofeedback treatment. Self-monitored pressure in both groups
      tended to decrease by the biofeedback treatment. Systolic and diastolic pressures
      as well as pulse rate decreased, skin temperature increased, and alpha-wave
      amplitude on electroencephalography increased during the therapy (p < .05).
      CONCLUSION: This treatment was effective in suppressing the pressor response to
      stress. Patients whose blood pressure increases with stress may be suited for
      biofeedback intervention.

PMID- 9178346
TI  - Presence and biochemical properties of a molluscan invertebrate angiotensin
      converting enzyme.
AB  - A soluble 65582.9 Da (in MALDI-TOF) angiotensin converting (ACE)-like enzyme has
      been purified by a captopril-Sepharose affinity column chromatography from the
      mollusk Mytilus edulis. This glycosylated peptidyl dipeptidase, with an N
      terminal sequence of LDPELSPGCFVANQAGGQLF, hydrolyses the Phe8-His9 bond (at pH
      8.4 and 37 degrees C) of angiotensin I with a high catalytic activity i.e. Km:
      168 microM and Kcat/Km: 262 s-1 mM-1. The hydrolysis of angiotensin I is
      inhibited by the specific ACE inhibitors captopril and lisonopril (Ic50 = 50 nM).
      This activity is increased by Cl- (optimal Cl- concentration 400 mM) and by Zn2+.
      This zinc metallopeptidase also attacks peptides having a Gly-His, Gly-Phe or a
      Phe-His bond in their sequence e.g. leucine-enkephalin (Kcat/Km: 1200 s-1 mM-1 or
      bradykinin (Kcat/Km: 2500 s-1 mM-1). Mytilus ACE displays properties of the C
      domain of human ACE, indicating a high degree of conservation during evolution.
      These results are consistent with an ACE activity implicated in metabolism of
      several neuropeptides in mollusks.

PMID- 9178347
TI  - Full-length and N-terminally truncated chicken intestinal diazepam-binding
      inhibitor. Purification, structural characterization and influence on insulin
      release.
AB  - Two forms of diazepam-binding inhibitor (DBI) have been purified from chicken
      intestine and identified as the intact avian polypeptide (residues 1-86) and a
      truncated variant (residues 35-86). At 10 nM concentration, both the intact and
      the truncated peptide suppress in vitro-monitored glucose-induced insulin release
      by 50 (p < 0.02) and 64% (p < 0.01) respectively. The truncation starts at a
      segment. -Thr-Val-Gly-Asp-, that is strictly conserved between characterized DBI
      species, indicating special restrictions on the structure. However, overall DBI
      conservation appears to be complex. A number of differently bioactive fragments
      with separate processings and tissue distributions have been observed, suggesting
      multiple functions of DBI and its sub-segments.

PMID- 9178348
TI  - N-terminal modifications to AKH-I from Locusta migratoria: assessment of
      biological potencies in vivo and in vitro.
AB  - To investigate the receptor tolerances to N-terminal variation, novel analogues
      to Locusta AKH-I (adipokinetic hormone) have been synthesized with modifications
      at the N-terminus. Analogues were made where the N-terminal pyroglutamyl residue
      was spaced further from the remainder of the molecule by the insertion of glycine
      residues between either pGlu1 and Leu2 (Gly1a-AKH-I, or Leu2 and Asn3 (Gly2a-AKH
      I and Gly2ab-AKH-I). Other modified hormones with N-terminal extensions were:
      (Ahx)n-AKH-I (Ahx. aminohexanoic acid); HPP(Ahx)n-AKH-I (HPP. hydroxyphenyl
      propionate) and Ac(Ahx)n-AKH-I (where n = 0-3). Finally, acetylated and non
      acetylated amino acids were substituted for pGlu1: Glu, Pro, Ala and Tyr. The
      effects of these modifications on biological potency were tested in the lipid
      mobilization assay in vivo and acetate uptake assay in vitro. The potency of AKH
      I was reduced much more by insertion of glycine between pGlu1 and Leu2, than
      between Leu2 and Asn3, perhaps suggesting that a hydrophobic residue is required
      adjacent to the pGlu for biological activity. In addition, a residue N-terminal
      to Leu2 is necessary for activity (i.e., [despGlu]-AKH-I is inactive) unless the
      free N-terminus is acetylated: Ac[despGlu]-AKH-I is active, but has low potency.
      The potencies of HPP(Ahx)0-3-AKH-I, Ac(Ahx)1-3-AKH-I and glycine-inserted
      analogues decreased consistently with increasing extension of the N-terminus away
      from the remainder of the molecule. However, potencies of the unblocked (Ahx)n
      AKH-I analogues did not, and potency in either assay did not appear related to
      the number of aminohexanoic residues. Similarly, while hormonal activity was
      retained by substitution of pGlu1 by Tyr, Pro, Ala or Glu in both assays,
      acetylation of the resulting analogues did not provide a consistent increase in
      potency, but actually decreased for AcGlu1-AKH-I compared with its unblocked
      analogue. HPP1-AKH-I was the most potent of the modified peptides tested, with
      almost the same potency in the assay in vitro as the natural peptide.

PMID- 9178349
TI  - Interaction of nicotine and a H2-receptor antagonist, famotidine, on gastrin and
      chromogranin A expression.
AB  - The purpose of this study is to examine the effect of nicotine on famotidine
      induced hypergastrinemia in the rat. In addition, the effects of nicotine on gene
      expression for gastrin and chromogranin A (CGA) in the stomach were examined.
      Famotidine treatment alone (20 mg/kg. 2 x/day for 14 days) increased serum
      gastrin levels significantly (P < 0.05) but not antral levels of gastrin mRNA and
      peptide. Nicotine treatment (12 mg/kg/d) alone did not affect serum gastrin
      levels; however, nicotine potentiated the hypergastrinemic action of famotidine.
      The hypergastrinemic action of nicotine was not mediated by a downregulation of
      stomach somatostatin (SRIF) since stomach SRIF mRNA levels were unaffected by
      nicotine treatment. Administration of nicotine and famotidine also upregulated
      stomach CGA gene expression (i.e., mRNA and protein levels) significantly.

PMID- 9178350
TI  - Capsaicin-evoked release of pituitary adenylate cyclase activating peptide
      (PACAP) and calcitonin gene-related peptide (CGRP) from rat spinal cord in vivo.
AB  - Capsaicin-evoked release of pituitary adenylate cyclase activating peptide
      (PACAP)-like immunoreactivity (LI) from rat spinal cord was examined in vivo. In
      anaesthetized rats, a catheter was inserted through the atlanto-occipital
      membrane into the subarachnoid space at the level of the sacral spinal cord for
      infusion of artificial cerebrospinal fluid. Another catheter was placed in the
      cisternal opening for outflow. Blood pressure was monitored and kept stable
      during the experiment. Perfusion samples were analyzed for PACAP and calcitonin
      gene-related peptide (CGRP) by radioimmunoassay. The addition of capsaicin (10
      microM) to the perfusate elevated the concentrations of PACAP-27-LI in the
      artificial cerebrospinal fluid by 177%, PACAP-38-LI by 93% and CGRP-LI by 692%.
      In view of the presence of PACAP-immunoreactive nerve fibres in the superficial
      layers of the dorsal horn and the expression of PACAP in the small sized neurons
      in the dorsal root ganglia, the findings suggest that PACAP is released into the
      artificial cerebrospinal fluid from C-fibres in the spinal cord. PACAP
      conceivably plays a modulating role in nociception.

PMID- 9178351
TI  - Are mu-opioid receptors involved in the control of endothelin-1 release from the
      pituitary gland in normal and dehydrated rats?
AB  - The objective of the present study was to investigate whether the endogenous
      opioids are involved in the control of endothelin-1 release from the pituitary
      gland. To test this hypothesis we have measured the peripheral plasma
      concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in
      the pituitary in response to opioid receptors blockade in euhydrated and 24 h
      water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body
      wt.) were given i.v. in both groups. Trunk blood was collected to determine
      hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the
      whole pituitary glands was performed by colloidal gold labeling. The quantitative
      analysis of irET-1 was carried out under a light microscope using a computerized
      image analyzer (MultiScan). RESULTS: (1) Twenty-four-hour dehydration resulted in
      marked increase of peripheral concentration of ET-1. Naltrexone injection induced
      a significant elevation of ET-1 plasma concentration in both, dehydrated and
      control animals. (2) The content of irET-1 in anterior and intermediate lobes of
      the pituitary in dehydrated rats was markedly higher than in control group. (3)
      Naltrexone injection caused a rapid and significant reduction irET-1 within the
      anterior, intermediate and posterior lobes in dehydrated and control animals.
      CONCLUSIONS: (1) An elevation of irET-1 in the pituitary gland and peripheral
      circulation in dehydrated animals may play a role in maintaining of water
      electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release
      from the pituitary in normal and dehydrated animals.

PMID- 9178352
TI  - Somatostatin- and urotensin II-related peptides: molecular diversity and
      evolutionary perspectives.
AB  - Recent advances in the fields of molecular cloning and peptide purification
      necessitate a reappraisal of our views concerning the evolution of the genes
      encoding somatostatin-related peptides. The currently widely held view that the
      genomes of tetrapods contain only the preprosomatostatin-I (PSS-I) gene, encoding
      somatostatin-14, with a second preprosomatostatin gene being expressed only in
      teleost fish is no longer tenable. Identification of genes encoding both
      somatostatin-14 and the somatostatin-related peptide, cortistatin in mammals,
      identification of the PSS-I and PSS-II preprosomatostatin genes in amphibia, and
      the isolation of gene products from at least two non-allelic preprosomatostatin
      genes in lampreys suggests the alternative hypothesis that duplication of the PSS
      I gene occurred early in evolution, predating or concomitant with the appearance
      of the chordates. We speculate that at least two somatostatin genes are expressed
      in all classes of vertebrates but these genes have evolved at very different
      rates. It is probable that the preprosomatostatin-II (PSS-II) gene, encoding
      [Tyr7, Gly10] somatostatin-14 or a related peptide, arose from a second
      independent duplication of the PSS-I gene in the ancestor of present-day teleost
      fish at a time after the divergence of the teleost stock from the line of
      evolution leading to tetrapods. The recent isolation of urotensin II, a peptide
      which contains a region of structural similarity but is not evolutionarily
      related to somatostatin-14, from the central nervous systems of lampreys,
      elasmobranchs and amphibia necessitates that we modify the accepted view that
      urotensin II is exclusively a product of the caudal neurosecretory system of
      teleost fish.

PMID- 9178353
TI  - Oxytocin increases nitric oxide production in the paraventricular nucleus of the
      hypothalamus of male rats: correlation with penile erection and yawning.
AB  - A dose of oxytocin (50 ng i.c.v.) that induces penile erection and yawning,
      increased the concentration of NO2- from 0.98 +/- 0.29 to 4.2 +/- 0.79 microM and
      of NO3- from 5.6 +/- 0.33 to 12.03 +/- 0.99 microM in the dialysate from the
      paraventricular nucleus of the hypothalamus of male rats, as measured by in vivo
      microdialysis. NO2- concentration was also increased by [Thr4, Gly7]-oxytocin
      (100 ng i.c.v. and oxytocin(8) (1 microgram i.c.v.) which also induced penile
      erection and yawning, but not by oxytocin(1-6) (1 microgram i.c.v.) or oxytocin
      (7-9) 1 microgram i.c.v.), which were unable to induce these behavioral
      responses. The oxytocin effect on NO2 concentration, penile erection and yawning
      was prevented by the oxytocin receptor antagonist. d(CH2)5,Tyr(Me)-Orn8-vasotocin
      (1 microgram i.e.v.) or by the nitric oxide synthase inhibitor, NG-nitro-1
      arginine methyl ester (200 micrograms i.c.v.), but not by the dopamine receptor
      antagonist, haloperidol (0.5 mg/kg i.p.). The nitric oxide scavenger, hemoglobin
      (200 micrograms i.c.v.), prevented oxytocin-induced NO2- concentration increase,
      but was unable to prevent penile erection and yawning. Methylene blue (300
      micrograms i.c.v.) an inhibitor of guanylate cyclase, was ineffective on oxytocin
      induced NO2- concentration increase, but prevented the behavioral responses. The
      results suggest that oxytocin induces penile erection and yawning by increasing
      nitric oxide synthase activity in the cell bodies of oxytocinergic neurons
      projecting to extra-hypothalamic brain areas and mediating the behavioral
      responses.

PMID- 9178354
TI  - Absence of response to oestrus induction and synchronization treatment is related
      to lipid mobilization in suckled beef cows.
AB  - Energy status, follicular growth, oestradiol and LH secretion were investigated
      in 17 suckled Charolais cows synchronised 59.0 +/- 3.6 days after calving with a
      10 day ear implant containing 3 mg of Norgestomet. The cows received 3 mg of
      Norgestomet and 5 mg of oestradiol valerate by IM injection at implant insertion
      (day 0) and 600 IU PMSG at implant removal (day 10). They were artificially
      inseminated (AI) 48 and 72 h after implant removal. Energy status was assessed by
      measuring weekly plasma concentrations of non-esterified fatty acids (NEFA), beta
      hydroxy-butyrate (BHB), glucose and insulin 7 weeks before AI. Progesterone
      plasma concentrations were measured during the same period to assess the presence
      of a functional corpus luteum. Follicular growth was followed daily by
      ultrasonography from day -3 to day 13. Oestradiol secretion was measured on day 
      3, day 6 and day 10 from five hourly samples. Oestradiol and LH plasma
      concentrations were measured hourly from 29 to 48 h after implant removal for
      seven cows. Cows were checked for pregnancy by ultrasonography 45 days after AI.
      Pregnant cows (P) were compared with non-pregnant cows (NP) for energy status,
      follicular growth, and oestradiol secretion by split-plot ANOVA. Two cows (11.8%)
      were cyclic before treatment, seven ovulated after treatment (41.2%) and five
      were found pregnant 45 days after AI (29.4%). There was no difference in body
      condition score and body weight between P and NP cows on day 0 (2.5 +/- 0.2 and
      685 +/- 24 kg vs 2.5 +/- 0.1 and 670 +/- 13 kg; P > 0.05). Mean plasma NEFA
      concentrations before treatment were significantly lower in P than in NP cows
      (218 +/- 29 mu eq/L vs 279 +/- 18 mu eq/L; P < 0.05). No significant differences
      between P and NP cows were found for BHB, glucose and insulin concentrations. P
      cows presented more medium sized follicles (5 mm < or = diameter < 10 mm) than NP
      females during the period of observation (2.65 +/- 0.19 vs 2.50 +/- 0.12; P =
      0.05). Plasma oestradiol concentrations were not different between P and NP cows
      on day -3 (8.4 +/- 0.7 pg/mL vs 7.7 +/- 0.4 pg/mL, P > 0.05), day 6 (10.4 +/- 0.6
      pg/mL vs 9.8 +/- 0.4 pg/mL, P > 0.05) but were higher in P than in NP cows on day
      10 (10.9 +/- 0.6 pg/mL vs 7.8 +/- 0.4 pg/mL; P < 0.05). After implant removal,
      oestradiol secretion only increased in P cows and a LH peak occurred whereas no
      increases in oestradiol (11.0 +/- 0.4 pg/mL vs 6.3 +/- 0.3 pg/mL, P < 0.05) and
      LH (6.0 +/- 0.5 ng/mL vs 1.2 +/- 0.5 ng/mL, P < 0.05) secretion were observed in
      NP cows. The conclusion was that follicular growth, oestradiol secretion,
      ovulation and pregnancy rate after oestrus synchronisation treatment are related
      to mobilization of energy stores before treatment in suckled beef cows in the
      same body condition score.

PMID- 9178355
TI  - Beneficial effects of Vero cells for developing IVF bovine eggs in two different
      coculture systems.
AB  - A Vero cell line was used for coculture of bovine in vitro fertilized eggs up to
      blastocyst stage in comparison with bovine oviductal epithelial cells (BOEC) in
      two culture systems: monolayers or microdrops. Inseminated oocytes cocultured for
      7 days with Vero cells in microdrops resulted in a significantly higher
      blastocyst rate compared to BOEC (29.5% vs 21.1%, respectively; P < 0.01). This
      difference was not significant in the monolayer coculture system although the
      blastocyst rate tended to be higher with Vero than with BOEC monolayers (27% vs
      22.3%, respectively). Interestingly, the coefficient of variation between
      replicates was lower in both Vero cell groups than in BOEC groups indicating that
      Vero cells may help reduce variability. Medium conditioned by Vero cells partly
      supported embryo development compared to coculture itself (14.6% vs 26.5%,
      respectively; P < 0.01). Blastocysts developed on Vero cells contained
      significantly more cells (142 +/- 39) than those developed on BOEC (88.8 +/-
      32.8, P < 0.001). Viability of blastocysts developed on Vero cells was evaluated
      by single transfer to 26 recipient heifers. Confirmed pregnancy rate after 3
      months was 58%, demonstrating their high viability.

PMID- 9178356
TI  - Morphological and functional characterization of bovine oviductal epithelial cell
      monolayers cultured on polarizing membranes.
AB  - Several characteristics of oviductal cells, cultured under either polarizing or
      nonpolarizing conditions, were studied. In vitro produced bovine embryos tested
      the embryotrophic abilities of the respective conditioned media. Conditioned
      medium from the apical face of polarized cell monolayers supported higher rates
      of development to blastocyst and expanded blastocysts. In contrast, conditioned
      medium from the basal face supported embryo development only to the 8-16 cell
      stage; however, these embryos were able to continue development to the morula
      stage when cultured in medium from the apical and basal faces, indicating total
      cell confluence and a clear functional polarization. At the ultrastructural
      level, cells cultured in polarizing conditions displayed characteristics nearer
      to the same cells in vivo and signs of a metabolic activity higher than that in
      cells cultured under non-polarizing conditions. It can be concluded that cell
      polarization, in our culture conditions, is beneficial to embryo development.

PMID- 9178357
TI  - Effects of simultaneous gestation and lactation in rabbit does on muscular
      characteristics of the youngs.
AB  - The aim of the experiment was to determine the influence of concurrent gestation
      and lactation in rabbit does on the post-natal growth and muscular
      characteristics of the progeny. Myosin heavy chain (MHC) isoform proportion,
      myofibrillar protein content and size of the myofibres were determined on day 29
      or day 70 in the semitendinosus muscle of young rabbits born from either
      simultaneously pregnant and lactating does (PL group) or from only pregnant does
      (P group). There were no significant differences in the weight of the young
      rabbits of the two groups throughout the post-natal period, despite a non
      significant reduction of birth weight by 9% in the PL group. On day 29, the
      proportion of perinatal MHC was higher (5.8% vs 2.3%) and that of the type-II
      isoforms was lower (91.5% vs 95.0%) in the PL group than in the P group (P <
      0.01). The simultaneous gestation and lactation affected the maturation of
      secondary fibres. On day 70, the proportion of the MHC isoforms was similar in
      the two groups. These results suggest that concurrent gestation and lactation
      delayed the myofibrillar maturation rate.

PMID- 9178358
TI  - Quantitative review of ruminal and total tract digestion of mixed diet organic
      matter and carbohydrates.
AB  - The mean response and main factors of variation (level of concentrate, nature of
      carbohydrate in the concentrate and level of intake) for organic matter, cell
      wall material, starch digestion and microbial synthesis in the gastrointestinal
      tract of ruminants were quantitatively reviewed using a data base involving 157
      papers. The ruminal digestion (mean +/- SE%) of organic matter, cell wall
      material, and starch were 45.2 +/- 11.2 (n = 553), 47.7 +/- 17.7 (n = 348), and
      74.1 +/- 16.2 (n = 140), respectively and the proportion of each component
      digested in the rumen in relation to total tract digestibility was 64.7 +/- 12.3,
      78.8 +/- 18.5 and 80.5 +/- 16.3, respectively. The efficiency of microbial
      synthesis (g of microbial protein/kg of organic matter truly fermented in the
      rumen) and the proportion of microbial nitrogen in the total amount of nitrogen
      leaving the stomachs (%) were, 23.6 +/- 9.3 (n = 320) and 55.1 +/- 16.5 (n =
      289), respectively. The ruminal digestion of organic matter increased by 2 points
      for every 10 percent increase in concentrate incorporation. The ruminal digestion
      of cell wall material was maximal when the concentrate incorporation in the diet
      was 30%. When the ruminal digestion of cell wall decreased, the substitution of
      ruminal digestion by intestinal digestion was partial (10%). The efficiency of
      microbial synthesis was optimal when the level of concentrate incorporation was
      40%. The nature of the carbohydrates in the concentrates had a significant effect
      on the efficiency of the microbial synthesis, which was higher (+6.6 g of
      nitrogen/kg of fermentable organic matter in the rumen) with slowly degradable
      starch (SS) or digestible fiber (DF) than with rapidly degradable starch (RS).
      Moreover, the mean depression of cellulolysis in the rumen was higher with RS (
      13 points) comparatively to SS (-7 points) or DF (-5 points).

PMID- 9178359
TI  - Influence of egg cannibalism on growth, survival and feeding in hatchlings of the
      land snail Helix aspersa Muller (Gastropoda, Pulmonata, Stylommatophora).
AB  - Under controlled conditions, growth, survivorship and several nutritional
      parameters (ingestion, egestion and assimilation) were measured weekly in
      hatchlings that either ate a conspecific egg after birth (cannibalistic) or not
      (non-cannibalistic) and in food-deprived individuals (control group).
      Subsequently, the snails were fed on Taraxacum officinale. After 4 days,
      cannibalistic snails were 1.3 times heavier than food-deprived snails and 100%
      survived (75.8% in the control group and 40% of the non-cannibalistic
      individuals). Mortality, particularly in smaller snails, might be a consequence
      of food deprivation. Nutritional and energetic gains of oophagy increased both
      future survivorship and growth. After 11 weeks, cannibalistic snails were 1.4
      times heavier and had higher survival rates than food-deprived ones although
      ingestion, egestion rates and assimilation efficiency were similar in both
      groups. The larger wet weight of cannibalistic snails after 4 days induced a
      higher food consumption and thus a higher growth rate. The influence of oophagy
      on life-history traits is discussed in relation to costs and benefits.

PMID- 9178360
TI  - Inhibition by TGF-beta 1 of the in vitro thymulin-stimulated proliferation of
      gonocytes from fetal rat testes.
AB  - The cytokine transforming growth factor beta 1 (TGF-beta 1) inhibits the growth
      of certain cells and the differentiation of others. A thymus hormone, thymulin,
      stimulated the proliferation of fetal male germ cells in explants of testes from
      13.5 gestation day rat fetuses. The way in which thymulin acts is unknown. Adding
      TGF-beta 1 to the culture medium blocked the response of the fetal male rat germ
      cells to thymulin. We suggest that TGF-beta 1 and thymulin may thus influence the
      same metabolic chain of events.

PMID- 9178361
TI  - Effect of injected vitamin A and level of dietary vitamin E on alpha-tocopherol
      status in gestating swine.
AB  - A 2 x 2 trial was conducted to determine the effects of injected vitamin A and
      dietary level of vitamin E on blood serum and tissue concentrations of alpha
      tocopherol during early gestation of gilts. Thirty-two crossbred gilts were fed a
      corn soybean meal basal diet supplemented with DL-alpha tocopheryl acetate to
      provide either 25 or 500 IU of vitamin E/kg of diet. Gilts were fed daily 1.9
      kg/gilt beginning 7 days before breeding until day 25 of gestation. Sixteen gilts
      were injected (i.m.) with 350,000 IU of retinol palmitate 7 days before breeding,
      at the time of breeding (d0), and 7 days after breeding. Blood samples were
      collected on day -7, 0, 7, and 24, and all gilts were slaughtered on day 25 of
      gestation. Supplemental vitamin E at 500 IU/kg of diet increased alpha-tocopherol
      concentrations (P < 0.01) in blood serum in all tissues examined, including
      reproductive and embryonic, except fat. Vitamin A injections had no effect (P >
      0.10) on blood serum alpha-tocopherol concentrations except on day 7 when a small
      increase (P < 0.06) was noted. Vitamin A injections had no effect (P > 0.10) on
      tissue alpha-tocopherol concentrations. Increasing dietary level of vitamin E
      increased blood serum and tissue alpha-tocopherol concentrations, and vitamin A
      injections had little or no effect on these concentrations during the early
      gestation of gilts.

PMID- 9178362
TI  - Utilization of algal polysaccharides by human colonic bacteria, in axenic culture
      or in association with hydrogenotrophic microorganisms.
AB  - The ability of different hydrolytic bacteria from the human colon to grow on
      various algal polymers (carrageenans, Palmaria palmata xylan, ulvan, desulphated
      ulvan and laminaran) was investigated and the interactions between Bacteroides
      thetaiotaomicron and H2-utilizing microorganisms (one methanogenic archaea and an
      acetogenic bacterium) were studied during laminaran degradation. None of the
      algal polysaccharides supported the growth of any of the hydrolytic species
      tested, except for laminaran, which allowed substantial growth of B
      thetaiotaomicron. This suggested that bacterial consortia were involved in algal
      polymer breakdown rather than one specific bacterial species. The presence of H2
      utilizing microorganisms did not increase the extent of laminaran degradation by
      B thetaiotaomicron. Whereas the decrease in formate and H2 concentrations
      attested to their utilization by both hydrogenotrophic microorganisms, the large
      increase in acetate production observed in the coculture with acetogenic bacteria
      was mainly due to acetogenic fermentation of sugars released during laminaran
      hydrolysis.

PMID- 9178363
TI  - GAP-43 phosphorylation by PKC in rat cerebrocortical synaptosomes: effect of
      antidepressants.
AB  - Recent evidence, including our previous work, indicates that changes in both c
      AMP and phospholipid-dependent protein kinases (PKA and PKC) may be involved in
      neuroadaptive mechanisms occurring in brain after repeated administration of
      antidepressants. The purpose of this study was to examine the phosphorylation of
      a major PKC substrate involved in modulation of neurotransmitter release, GAP-43,
      in a synaptosomal preparation from rat cerebral cortex after repeated
      administration of fluxetine (FL) and desipramine (DMI). Groups of male rats were
      treated for 21 days with either FL (5 mg/kg/day, i.p.), DMI (10 mg/kg/day, i.p.)
      or vehicle (controls) and cortical synaptosomes were prepared 48 h or 24 h after
      the last injection. Synaptosomal membrane proteins were resolved by SDS-PAGE.
      Western immunoblotting and immunoprecipitation with anti-GAP-43 antibody have
      identified the GAP-43 protein as a single distinct band of apparent molecular
      weight of 56 kDa. The extent of phosphorylation of GAP-43 protein by native PKC
      in synaptosomes of rats treated with either FL or DMI was not significantly
      different from that observed in control animals. The previously observed
      suppression of basal PKC activity in rat cortical synaptosomes by FL and DMI
      treatment was thus not reflected in altered GAP-43 phosphorylation. It is thus
      unlikely that changes in GAP-43 phosphorylation are involved in antidepressant
      induced modulation of 5-HT release.

PMID- 9178364
TI  - Human placental ecto-enzymes: studies on the plasma membrane anchorage and effect
      of inhibitors of ATP-metabolizing enzymes.
AB  - The human placental microvillar membrane contains several ectoenzymes, including
      5'-nucleotidase, alkaline phosphatase and ATP-diphosphohydrolase (ATP-DPH), which
      might be involved in the extracellular metabolism of nucleotides. The type of
      anchorage to the plasma membrane of the two first enzymes has been shown to be
      via a glycosyl-phosphatidylinositol. In the present study, using an enzymatic
      approach, we show that the ATP-DPH should be attached to the plasma membrane
      through a different type of anchorage. We were also interested in the search of
      compounds which could interact differentially with this enzyme to be used as a
      tool for studying the other two hydrolytic enzymes in the presence of ATP-DPH.
      Here we report several inhibitors of ecto-ATPases which seem to be a useful tool
      for studying these three enzymes.

PMID- 9178365
TI  - Clinical value of cytokine antagonists in infectious complications.
AB  - Plasma levels of antiinflammatory compounds (which counteract inflammation,
      cortisol, IL-1 receptor antagonist, IL-1ra; soluble IL-2 receptor, sIL-2r,
      soluble intercellular adhesion molecule-1, sICAM-1; interleukin-10, IL-10) were
      synchronously determined in a consecutive series of 25 patients with severe
      bacterial infections. Serum levels of cortisol, IL-1ra, sIL-2r, sICAM-1 and IL-10
      were significantly higher in patients with infection compared with healthy
      volunteers. Bacterial infection results in the production of inflammatory and
      proinflammatory cytokines from macrophage/monocyte, which are thought to be
      involved in the pathogenesis of systemic inflammatory response syndrome (SIRS).
      We found that counter-inflammatory compounds can also be released during
      infectious insults. These results suggested that the biological activity of
      inflammatory mediators is inhibited by natural antiinflammatory compounds, and
      the body itself might down-regulate excessive inflammatory cascades through
      counteracting the inflammatory responses and restore homeostasis.

PMID- 9178366
TI  - Potentiation of acetaminophen hepatotoxicity by acute physical exercise in rats.
AB  - Effects of acute physical exercise on the acetaminophen-induced hepatotoxicity
      were examined in adult female rats. Rats were forced to move at a speed of 10
      m/min for 2 hr in a rotating cage. Immediately following the exercise bout rats
      were treated with acetaminophen (APAP; 700 mg/kg, i.p.). The physical exercise
      enhanced the hepatotoxicity of APAP as shown by increases in alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured
      24 hr following the treatment. A significant decrease in hepatic glutathione
      (GSH) was observed in the rats forced to exercise suggesting that the enhancement
      of APAP hepatotoxicity was associated with the depression of this endogenous
      tripeptide. The role of adrenergic stimulation in the exercise-induced hepatic
      GSH depression was examined by pretreating the animals with a receptor specific
      adrenergic antagonist, such as prazosin HCl (15 mg/kg, i.p.), propranolol HCl (15
      mg/kg, i.p.), and yohimbine HCl (15 mg/kg, i.p.) 15 min prior to the exercise
      bout, but neither of the antagonists prevented the GSH depression. Administration
      of alpha-tocopherol acetate (450 mg/kg/day for 3 days and 150 mg/kg on day 4,
      i.p.) did not affect the exercise-induced GSH depression or lipid peroxidation in
      liver homogenates as determined by increases in malondialdehyde formation. These
      results suggest that neither adrenergic stimulation nor oxidative stress plays a
      significant role in the enhancement of APAP hepatotoxicity and hepatic GSH
      depression induced by acute physical exercise.

PMID- 9178367
TI  - Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing
      enzyme activities in mice: possible mechanism for anticonvulsant activity against
      4-O-methylpyridoxine-induced convulsions.
AB  - Anticonvulsant effects of bilobalide, one of the constituents of Ginkgo biloba
      L., on the convulsions induced by 4-O-methylpyridoxine (MPN) were investigated in
      mice. Bilobalide reduced the duration and incidence of MPN-induced convulsions
      depending on its dose and the period of treatment. In addition, the
      anticonvulsant effect was manifested more than 24 hours after treatment and the
      effect lasted for 7 days after its withdrawal. In mice treated with bilobalide
      (30 mg/kg, p.o., once a day for 4 days), hepatic 7-methoxycoumarin O-demethylase
      activity was potentiated, and the disappearance of MPN in blood after MPN
      injection was faster than in controls. From these results, it is assumed that the
      anticonvulsant effect of bilobalide against convulsions induced by MPN partly
      involves modulation of hepatic drug-metabolizing enzyme activity, which leads to
      accelerated elimination of MPN.

PMID- 9178368
TI  - Endothelial dysfunction in the perfused kidney from the streptozotocin-induced
      diabetic rat.
AB  - The vasodilator effects of acetylcholine were examined in methoxamine
      preconstricted perfused kidneys taken from rats with streptozotocin (STZ)-induced
      diabetes. Acetylcholine-dependent vasodilatation was significantly weaker in STZ
      induced diabetic rats than in age-matched controls, and it was completely
      abolished by treatment with 60 mM K+ plus NG-nitro-L-arginine (L-NNA) plus
      methylene blue in the control rats and was significantly but not completely
      inhibited by these treatment in the diabetic rats. Although acetylcholine-induced
      vasodilation was not affected by indomethacin in control rats, it was attenuated
      by indomethacin in the diabetic rats. Arachidonic acid-induced vasoconstriction
      was slightly but significantly increased in the diabetic rats. Acetylcholine
      increased significantly the level of 6-keto-prostaglandin F1 alpha in the
      effluent from perfused kidneys from diabetic rats. These results suggest that the
      endothelium-dependent vasodilatation induced by acetylcholine in the renal
      vascular bed of age-matched control rats is due to the release of nitric oxide
      (NO) and endothelium-derived hyperpolarizing factor (EDHF), whereas the
      vasodilatation induced by acetylcholine in the STZ-diabetic kidney also involves
      prostaglandin I2 as well as NO and EDHF.

PMID- 9178369
TI  - Proinflammatory cytokines downregulate gene expression and activity of
      constitutive nitric oxide synthase in porcine pulmonary artery endothelial cells.
AB  - We evaluated the effects of cytokines on the catalytic activity and expression of
      porcine pulmonary artery endothelial cell (PAEC) constitutive (eNOS) and
      inducible (iNOS) isoforms of nitric oxide synthase (NOS). Exposure of PAEC to the
      combination of IFN-gamma, TNF-alpha, and IL-1 beta did not alter iNOS activity in
      cytosolic and membrane fractions but significantly (p < 0.01) reduced eNOS
      activity in the membrane fraction, but not in the cytosolic fraction, after a 24
      h exposure. The cytokine-induced loss of membrane fraction eNOS activity was
      associated with significant reductions of eNOS mRNA and protein content (p < 0.01
      for both). Treatment with the protein synthesis inhibitor, cycloheximide, but not
      the transcriptional inhibitor actinomycin D prevented cytokine-induced reduction
      of eNOS mRNA expression. These results suggest that cytokine-induced loss of
      catalytic activity of eNOS is associated with a reduction in eNOS mRNA and
      protein mass and that cytokines alter eNOS mRNA stability. Inhibition of protein
      synthesis prevented reduction of eNOS mRNA by cytokines, suggesting that the
      mechanism by which cytokines alter eNOS mRNA stability involves protein
      synthesis.

PMID- 9178371
TI  - Metabolism of tacrolimus (FK 506) in rat liver microsomes. Effect of rifampin and
      dexamethasone.
AB  - The in vitro metabolism of tacrolimus (TAC, FK 506) was investigated in the liver
      microsomes prepared from normal rats as well as rats treated with dexamethasone
      (DEX) and rifampin (RIF). The rate of tacrolimus metabolism was similar in
      control and RIF treated rat liver microsomes, whereas it significantly increased
      in microsomes obtained from dexamethasone treated rats. Seven different possible
      metabolites were identified in the microsomal preparations from rats treated with
      rifampin or dexamethasone whereas the microsomes from the control rats failed to
      produce the mono-demethylated and monohydroxylated metabolite of TAC (TAC+2, m/z
      = 805.5). There was an apparent difference in the amount of individual
      metabolites formed in different groups. This indicates quantitative differences
      in the induction of cytochrome P450 3A, an enzyme sub family known to be
      primarily responsible for tacrolimus metabolism. Lack of induction of tacrolimus
      metabolism by rifampin can be attributed to the lack of effect of rifampin in
      inducing cytochrome P450 3A in rats.

PMID- 9178370
TI  - The Na+/K+ATPase mediates the alpha 1-adrenoceptor stimulated increase in 86Rb(+)
      uptake in isolated ventricular cardiomyocytes from adult rat heart.
AB  - The aim of the present study was to identify the mechanism(s) responsible for the
      alpha 1-adrenoceptor stimulated increase in potassium uptake in ventricular
      cardiomyocytes isolated from adult rat heart. The Na+/K+ATPase blocker ouabain
      the Na+/K+/2Cl(-)-cotransporter blocker bumetanide, the Na+/H(+)-exchanger
      blocker HOE 694 and the potassium channel blocker 4-aminopyridine were used as
      experimental tools. 86Rb+ was used as potassium analogue. The basal 86Rb(+)
      uptake rate was 0.25 +/- 0.01 ml/g protein x min. Maximal alpha 1-adrenoceptor
      stimulation increased the 86Rb(+)-uptake 38 +/- 2%. Ouabain dose dependently
      eliminated the alpha 1-adrenoceptor stimulated response with a -logIC50-value of
      3.64 +/- 0.23. Bumetanide did not affect the stimulated response, and there was
      no effect of bumetanide on the ouabain sensitive component. HOE 694 and 4
      aminopyridine had no effect on the stimulated 86Rb(+)-uptake. Ouabain and HOE 694
      also dose dependently inhibited a portion of the basal 86Rb(+)-uptake (about 60%
      and 20%, respectively), but there was no effect of bumetanide or 4-aminopyridine
      on the basal 86Rb(+)-uptake. The results show that the Na+/K+ATPase alone
      mediates the alpah 1-adrenoceptor stimulated increase in potassium uptake in this
      preparation of ventricular cardiomyocytes isolated from adult rat heart.

PMID- 9178372
TI  - Lack of long-term facilitation of ventilation after exposure to hypoxia in goats.
AB  - Episodic hypoxia has been shown to induce augmented normoxic ventilatory drive or
      long-term facilitation (LTF, continued hyperventilation after termination of
      hypoxic stimulation) in awake dogs and awake goats. The main objective of these
      experiments was to examine whether continuous isocapnic hypoxia in awake goats
      elicits LTF and additionally, to determine if goats exhibit hypoxic ventilatory
      decline (roll-off) during the hypoxic exposure. Goats were exposed to either 4 h
      of isocapnic hypoxia (n = 10) or 30 min of isocapnic hypoxia (n = 7). Ventilation
      (VE), tidal volume and frequency were measured before, during and following the
      end of the isocapnic hypoxia (PaO2 40 Torr) exposure. During the 4 h period of
      hypoxia, VE increased in a time-dependent manner in a typical pattern of
      acclimatization, reaching a mean of 40.8 +/- 3.6 L/min at the end of 4 h. Five
      minutes after return to normoxia, VE was 13.0 +/- 0.8 L/min, not different than
      control VE (13.1 +/- 0.9 L/min) measured prior to the hypoxic exposure and
      remained unchanged from this value for another 30 min. During the 30 min hypoxic
      exposure, VE increased upon exposure to hypoxia, remained significantly elevated
      throughout the hypoxic exposure, but promptly returned to control levels upon
      return to normoxia. These results indicate that continuous isocapnic hypoxia
      elicits neither long term facilitation of ventilation nor hypoxic ventilatory
      decline in awake goats.

PMID- 9178373
TI  - Passive constriction of the upper airway during central apneas: fiberoptic and
      EMG investigations.
AB  - We studied five adult male patients with central sleep apnea syndrome (> 75% of
      the monitored events being central) during sleep using a fiberoptic scope and EMG
      monitoring of the superior and middle constrictors of the pharynx and the
      genioglossus and geniohyoid muscles. The fiberoptic investigation revealed a
      spontaneous decrease in the size of the airway during central apneas, without
      negative intrathoracic pressure or activation of the superior and middle
      pharyngeal constrictor muscles. We found a mean maximum decrease of 71 +/- 7% in
      the cross-sectional area of the airway and an absence of superior-middle
      pharyngeal constrictor EMG discharge. We did not observe any complete collapses
      of the airway.

PMID- 9178374
TI  - Cardiorespiratory effects of L-glutamate microinjected into the rat ventral
      medulla.
AB  - We investigated the cardiorespiratory effects elicited by microinjections of L
      glutamate (L-glu, 25 nmol, 200 nl) at various sites in the ventral medulla (VMS)
      of urethane-anesthetized rats. The results demonstrated that regions responsive
      to the drug are located along a column in the VMS extending from the VI cranial
      nerve to the first cervical nerve in the caudal medulla. Within this column three
      breathing patterns were elicited from four distinct areas. In the most rostral
      and caudal portion of this hypothetical column, the breathing patterns observed
      in response to L-glu were similar and characterized by increases in minute
      ventilation, tidal volume, inspiratory drive, respiratory frequency, mean
      arterial blood pressure (MAP) and heart rate (HR). In the regions located between
      the areas described above two different breathing patterns were obtained without
      significant changes in MAP or HR. These patterns were characterized by decreases
      and increases in the respiratory indices analyzed, with the exception of
      respiratory frequency, which decreased in both regions. These results suggest
      that within the VMS discrete areas may act as functional units modulating
      cardiorespiratory responses while in others these functions are spatially
      segregated.

PMID- 9178375
TI  - gamma-Aminobutyric acid contributes to modulation of cardiorespiratory control
      after chronic ventilatory loading.
AB  - Diseases imposing chronic ventilatory loads may depress ventilation and cause
      chronic hypercapnia. This may be a result of mechanical loading imposed on pre
      existing decreased respiratory drive or functional alteration of neural circuits
      involved in ventilatory control. To evaluate these possibilities, chronic
      resistive airway loading was imposed in rats via a circumferential tracheal band
      which tripled tracheal resistance (obstructed group). Sham surgery was performed
      in controls. After 8 weeks, animals were anesthetized (urethane) and tracheostomy
      performed relieving increased tracheal resistance. The ventral medullary surface
      (VMS) was exposed and the intermediate area (IA) identified. The integrated
      diaphragm EMG (EMGDI) was recorded. The obstructed group was hypercapnic while
      controls were eucapnic (PCO2, 45.1 +/- 7.9 vs. 37.6 +/- 3.4 Torr; P < 0.001).
      Respiratory rate (RR) remained lower in obstructed than in control animals
      despite relief of the resistive load by tracheostomy (58.5 +/- 5.1 vs. 75.4 +/-
      5.4 bpm; P < 0.05). Application of 1 mM bicuculline soaked pledgets (BIC) to the
      IA of the VMS significantly increased EMGDI in obstructed but not in control
      animals (27.5 +/- 5.5 vs. 5.2 +/- 4.4%; P < 0.006). RR was unaffected. Mean
      arterial pressure increased with BIC in obstructed but not control animals (23.0
      +/- 6.5 vs. 4.5 +/- 3.5%; P < 0.02). These data suggest that alteration of
      cardiorespiratory control occurs during chronic resistive hypercapnic loading and
      that GABAergic neurons in the VMS participate in this adaptive response.

PMID- 9178377
TI  - Morphological determinants of peripheral lung mechanical changes induced by
      capsaicin.
AB  - We studied the morphological elements associated with airway and pulmonary tissue
      responses to capsaicin in mechanically ventilated guinea pigs. Lungs were excised
      and frozen in liquid nitrogen 3 and 20 min after capsaicin infusion (1 or 100
      micrograms/kg i.v.). Using image analysis, we obtained contraction index (CI) and
      peribronchial edema area (CUFF) for both central (C) and peripheral airways (P).
      We also assessed alveolar size (mean linear intercepts, Lm) and tissue distortion
      (standard deviation of the number of intercepts, SDI). Multiple regression
      analysis showed significant associations between pulmonary tissue resistance
      (Rti) and CUFFP (p < 0.001); pulmonary dynamic elastance and SDI (p = 0.002); and
      airway resistance and CUFFC (p < 0.0001). Our results suggest that increases in
      Rti observed in guinea pigs after capsaicin infusion are primarily dependent on
      changes in the small airways, mainly peribronchiolar edema; the increase in lung
      elastance is related to distortion of parenchymal tissues; and large airway edema
      contributes significantly to airway resistance.

PMID- 9178376
TI  - Contribution of vagal afferents to breathing pattern in rats with lung fibrosis.
AB  - In anesthestized male Wistar rats with bleomycin-induced lung fibrosis we
      examined the influence of lung vagal non-myelinated and myelinated afferents in
      setting breathing pattern. Fourteen days after intratracheal instillation of
      bleomycin, lung compliance, total lung capacity (TLC) and inspiratory capacity
      were reduced while functional residual capacity and residual volume were
      increased. Baseline tidal volume (VT) was decreased and frequency (fR) increased
      in the bleomycin treated rats compared with controls. Selective vagal C-fiber
      blockade did not affect fR or VT in any group. Vagotomy resulted in an increase
      in VT and decrease in fR in both groups with the percent increase in VT/TLC and
      decrease in fR being significantly greater in the bleomycin rats compared with
      controls. Vagotomy also attenuated the significantly elevated PCO2 in the
      bleomycin treated rats suggesting that bleomycin-induced alterations in breathing
      pattern contribute to blood gas abnormalities. We conclude that vagal myelinated
      afferents contribute to the rapid shallow breathing in bleomycin treated rats.

PMID- 9178378
TI  - Respiratory mechanics after chronic diethylcarbamazine.
AB  - This study was performed to evaluate the role of diethylcarbamazine (DEC), the
      drug of choice for treating Lymphatic Filariasis and Tropical Pulmonary
      Eosinophilia, on respiratory mechanics of higid rats. Thus, during 30 days two
      groups of six rats each received intraperitoneally either isotonic saline
      solution, or 12 mg/kg per day of DEC. Thereafter, they were sedated,
      anesthetized, paralysed and mechanical ventilation followed. After airway
      occlusion at end inspiration, respiratory system, pulmonary and chest wall
      resistive pressures (delta P1,rs, delta P1,L, and delta P1,w, respectively) and
      viscoelastic/inhomogeneous pressures (delta P2,rs, delta P2,L and delta P2,w,
      respectively) were determined in each group. Total delta pressures (delta Ptot)
      were calculated as the sum of delta P1 and delta P2, yielding the values of delta
      Ptot,rs, delta Ptot,L, and delta Ptot,w, respectively. Respiratory system, lung
      and chest wall static (Est,rs, Est,L, and Est,w, respectively) and dynamic
      elastances (Edyn,rs, Edyn,L, and Edyn,w, respectively), and the corresponding
      delta elastances (calculated as Edyn-Est) were also obtained. DEC therapy
      significantly decreased delta Ptot,rs, delta P tot,L, delta P2,rs, delta P2,L,
      Est,ts, Est,L, delta Ers and delta EL, in relation to the respective control
      values. It can be concluded that DEC decreases respiratory system impedance,
      being potentially useful for allowing airway dilation at the lung periphery.

PMID- 9178379
TI  - Oxygen transport with oscillations of inspired oxygen concentration.
AB  - A theoretical model predicts that forced inspiratory oxygen concentration
      oscillations can be used to recover cardiorespiratory data and elicit information
      about the oxygen transport system (Hahn, 1996). The effects of hypoxia on the
      penetration of these generated oxygen oscillations into arterial and venous blood
      were explored in dogs exposed to a graded severity of hypoxia. Continuously
      recorded sinusoidal oxygen oscillations in the respired partial pressure, blood
      tension and mixed-venous saturation show that the transmission of forced oxygen
      oscillations from the lungs to the arterial blood depends on the mean arterial
      saturation. When mean inspired oxygen is high enough to fully saturate arterial
      haemoglobin, an inspired oscillation can only be transmitted in the blood as an
      oscillation in oxygen tension. However, in the presence of arterial hypoxaemia,
      oscillations in both the oxygen saturation and partial pressure of arterial blood
      are observed. Under these conditions, the oxygen saturation and partial pressure
      oscillations are also transmitted to mixed-venous blood. Our data illustrates
      that the link between the arterial and mixed-venous oscillations is non-linear
      and dependent on the sigmoidal binding relationship between oxygen and
      haemoglobin.

PMID- 9178380
TI  - A reconciliation of continuous and tidal ventilation gas exchange models.
AB  - Continuous-ventilation mathematical gas exchange models are widely used since
      their analytical equations are amenable to physiological interpretation. They
      describe qualitatively the respiratory system's response to changing
      physiological conditions, but do not calculate accurate values for respiratory
      parameters when experimental tidal ventilation expired gas data are inserted into
      their analytical expressions. A simple mathematical expression is presented to
      reconcile continuous and tidal ventilation gas exchange models. Tidal ventilation
      experimental data can then be inserted into conventional continuous ventilation
      equations to produce more accurate measures of lung volume. This hypothesis is
      tested with controlled experimental tidal ventilation tracer gas data obtained
      from both wash-out and forced inspired sinusoid experiments, using a mechanical
      lung model with known volume; tidal volume, VT; and series 'airway' dead space
      VD. We show that the subtraction of 1/2 (VT + VD) from the lung volume calculated
      from the continuous ventilation theory can produce lung volume measurements which
      agree with the true lung volume to within +/-5%, for physiological lung volume
      values, for both wash-out and forced sinusoid techniques.

PMID- 9178381
TI  - CPR training without an instructor: development and evaluation of a video self
      instructional system for effective performance of cardiopulmonary resuscitation.
AB  - Traditional classroom-based instruction of cardiopulmonary resuscitation (CPR)
      has failed to achieve desired rates of bystander CPR. Video self-instruction
      (VSI) is a more accessible alternative to traditional classroom instruction
      (TRAD), and it achieves better CPR skill performance. VSI employs a 34-min
      training tape and an inexpensive manikin. VSI combines simplified and reordered
      content focusing on the delivery of one-rescuer CPR with the 'practice-as-you
      watch' approach of an exercise video. Performance of CPR skills immediately
      following VSI was compared to performance immediately following TRAD using an
      instrumented manikin, a valid and reliable skill checklist, and an overall
      competency rating. Compared with TRAD subjects, VSI subjects performed more
      compressions correctly (P < 0.001), more ventilations correctly (P < 0.001), and
      more assessment and sequence skills correctly (P < 0.001). TRAD subjects
      delivered twice as many compressions that were too shallow, and underinflated the
      lungs twice as often. VSI subjects were rated 'competent' or better 80.0% of the
      time, compared with TRAD subjects, who achieved this rating only 45.1% of the
      time (P < 0.001). TRAD subjects were rated to be 'not competent' in performing
      CPR nearly 10 times more often than VSI subjects (P < 0.001). Subjects 40 years
      of age and older performed better after VSI than after TRAD. Superior skill
      performance among subjects exposed to VSI persisted 60 days following training.
      VSI has the potential to reach individuals unlikely to participate in TRAD
      classes because of its greater convenience, lower cost, and training in about
      0.50 h compared with 3-4 h for TRAD classes.

PMID- 9178382
TI  - Improving cardiopulmonary resuscitation skills retention: effect of two
      checklists designed to prompt correct performance.
AB  - Previous research has shown that regardless of an individual's experience, life
      support skills such as cardiopulmonary resuscitation (CPR) are poorly performed
      as soon as 1 month following training. The purpose of this study was to compare
      the effects of two checklists designed to prompt correct CPR performance. We
      compared the performance of 169 undergraduate students, at the time of course
      assessment, with retention testing that occurred 2 months following the course
      assessment. Students were randomly assigned to a control group, a short version
      of a CPR checklist and a longer more detailed version. Two groups of variables
      were created: procedural and compression-ventilation variables. In addition, an
      overall-performance variable was created, summarizing performance on the
      procedural variables. Binary variables were assessed with chi 2-tests of
      independence. One-way ANOVAs, using 'group' as the between-subjects factor, were
      used to assess each continuous variable. Comparisons between groups yielded
      significant differences of P < 0.05. The long checklist generally led to superior
      performance on the procedural variables. The results support the hypothesis that
      remembering the steps of CPR is too complex for some. Though preliminary, the
      findings of this study indicate that the detailed checklist was an effective
      strategy to improve the post-course performance of CPR.

PMID- 9178383
TI  - Outcome of out-of-hospital cardiorespiratory arrest in south Glamorgan.
AB  - During 138 weeks an emergency medical service (EMS) of mixed skill-level
      attempted to resuscitate 954 patients from prehospital cardiac arrest (883
      attempts per million population per year); 75% of the arrests were of cardiac
      cause. This paper is one of the first analyses from europe to use the 'Utstein
      template' to report outcomes of such arrests. In cases where an arrest rhythm
      could be recorded, 38.4% were ventricular fibrillation (VF), 45.5% were
      asystolic, and the remainder were either electromechanical dissociation or
      respiratory arrests. Using univariate analysis factors associated with a greater
      likelihood of survival include the presence of a witness, bystander-initiated
      cardiopulmonary resuscitation (CPR), early CPR and VF as the arrest rhythm.
      Twenty of 155 cases (13%) survived where VF arrest was witnessed by non-EMS
      personnel.

PMID- 9178384
TI  - Quality of mechanical, manual standard and active compression-decompression CPR
      on the arrest site and during transport in a manikin model.
AB  - The quality of mechanical CPR (M-CPR) was compared with manual standard CPR (S
      CPR) and active compression-decompression CPR (ACD-CPR) performed by paramedics
      on the site of a cardiac arrest and during manual and ambulance transport. Each
      technique was performed 12 times on manikins using teams from a group of 12
      paramedic students with good clinical CPR experience using a random cross-over
      design. Except for some lost ventilations the CPR effort using the mechanical
      device adhered to the European Resuscitation Council guidelines, with an added
      time requirement of median 40 s for attaching the device compared with manual
      standard CPR. Throughout the study, in comparison with mechanical CPR the quality
      of CPR with either manual method was significantly worse. In particular, there
      were considerable individual variations during stretcher transport. With S-CPR
      and ACD-CPR the median compression times were 38 and 31%, significantly lower
      than the recommended 50%, and 46-98% of the decompression efforts with ACD-CPR
      were too weak, particularly during transport on the stairs. With both manual
      methods, there were no significant differences in the CPR effort between the site
      of the arrest and the ambulance transport. However, compression rates were
      reduced and became more erratic during stretcher transport to the ambulance. When
      walking horizontally, a median of 19% of S-CPR compressions and 84% of ACD-CPR
      compressions were to weak. On the stairs, 68% of S-CPR compressions and 100% of
      ACD-CPR compressions were too weak. In conclusion, when evaluated on a manikin,
      in comparison with manual standard and ACD-CPR, mechanical CPR adhered more
      closely to ERC guidelines. This was particularly true when performing CPR during
      transport on a stretcher.

PMID- 9178385
TI  - Combined epicardial-transthoracic electrode paddle placement: a method for
      defibrillation during open-chest cardiac resuscitation.
AB  - We present a case of open-chest cardiac massage where ventricular fibrillation
      developed and a direct current shock was required. In the absence of 'surgical'
      electrode paddles, standard paddle electrodes were used; one small electrode was
      placed directly on the exposed epicardial surface and the second electrode was
      placed on the lateral chest wall. Defibrillation was achieved with a 100 J shock.
      This combined epicardial-transthoracic electrode paddle placement technique
      allows defibrillation to be accomplished when open chest cardiac massage is being
      performed and no 'surgical' electrode paddles are available.

PMID- 9178386
TI  - Open-chest cardiac massage without major thoracotomy: metabolic indicators of
      coronary and cerebral perfusion.
AB  - OBJECTIVE: To compare the coronary and cerebral perfusion achieved using a novel
      method of minimally-invasive, direct cardiac massage to that obtained using
      bimanual, open-chest cardiac massage. DESIGN: Prospective, controlled animal
      study with repeated measures. SETTING: University research laboratory. SUBJECTS:
      Large domestic swine. INTERVENTIONS: Aortic, coronary sinus, jugular venous and
      pulmonary artery catheters were placed. Following an equilibration period,
      ventricular fibrillation was induced. After 4 min of untreated ventricular
      fibrillation, animals underwent bimanual, open-chest cardiac massage (N = 6) or
      minimally-invasive, direct cardiac massage using a novel device for direct
      cardiac compression (N = 6). Adrenaline was administered at a dose of 1 mg
      intravenously every 5 min. MEASUREMENTS: Systemic metabolic parameters, (arterial
      PO2, PCO2 and lactate concentration) and coronary sinus and jugular venous
      metabolic parameters (pH, PVO2, SVO2, PVCO2 and lactate concentration) were
      measured and calculated (coronary sinus/jugular-arterial SVO2, coronary
      sinus/jugular-arterial PCO2 and lactate differences) at baseline and at 10, 20
      and 30 min following induction of ventricular fibrillation. Animals were
      euthanised after 30 min with no attempt at defibrillation. MAIN RESULTS: Oxygen
      tension and oxygen saturation of coronary sinus blood declined significantly
      during the experimental period, but no differences were noted between treatment
      groups. The coronary sinus-arterial oxygen saturation difference increased during
      the study with no significant differences between groups. Coronary sinus PCO2 and
      the coronary sinus-arterial PCO2 difference increased significantly in both
      experimental groups during cardiac massage. No inter-group differences were
      noted. A similar relationship was noted in coronary sinus lactate values. The
      coronary sinus-arterial lactate difference displayed a positive balance at all
      intervals with no differences noted between group values. The oxygen tension and
      oxygen saturation of jugular venous blood, were reduced from baseline levels with
      both treatments. The jugular-arterial oxygen saturation difference increased in
      both groups compared to baseline values. Between group values were significantly
      different only at the 20 min interval. Both the jugular venous PCO2 and the
      jugular-arterial PCO2 gradient were elevated at all intervals, but no inter-group
      differences were noted. Jugular venous lactate concentration rose steadily with
      time in both groups. No significant increase in the jugular-arterial lactate
      gradient was noted at any time point. CONCLUSIONS: Minimally-invasive, direct
      cardiac massage provides coronary and cerebral perfusion similar to that achieved
      using standard open-chest cardiac massage. This method may provide a more
      effective substitute for standard, closed-chest cardiac massage in cases of
      refractory cardiac arrest.

PMID- 9178388
TI  - The relationship between airway carbon dioxide excretion and cardiac output
      during cardiopulmonary resuscitation.
AB  - There is currently no practical method for determining cardiopulmonary
      resuscitation (CPR) efficacy in the field. We investigated the relationship
      between the volume of carbon dioxide (CO2) excreted in the airway (CO2EX) when
      tidal volume and respiratory rate are controlled, and cardiac output (CO), an
      indicator of CPR efficacy, to determine the potential of CO2EX as a practical
      noninvasive field monitor of CPR efficacy. Thirteen mongrel dogs were
      anesthetized, instrumented and ventilated 13 times/min at a fixed tidal volume
      with an infrared airway CO2 sensor. CO2EX = (PCO2/bar. press) x (tidal vol) x
      (breaths/min), and expressed in ml/min per kg. Sequences of control, CPR with 3-4
      different compression forces, and recovery measurements were recorded 10-15
      times/animal. CO2EX and CO fell simultaneously with ventricular fibrillation. CPR
      immediately increased CO2EX and CO. Both changed consistently and in the same
      direction as compression force. Return of spontaneous circulation immediately
      increased CO2EX and CO above controls, with a gradual return to control levels.
      CO2EX was always below 8 ml-CO2/min/kg during CPR and above this during
      spontaneous circulation. With alveolar ventilation controlled, CO2 movement is
      regulated by CO, CO distribution and CO2 stores shifts. Normally, CO accounts for
      15% of CO2EX variability. In this study CO accounted for > or = 65% of CO2EX
      variability during CPR, indicating CO2EX changes were primarily due to CO
      changes. When ventilation is controlled, CO2EX during CPR reliably tracks changes
      in CO. Therefore, CO2EX may provide a practical noninvasive method of determining
      CPR efficacy as the CPR is being performed.

PMID- 9178387
TI  - High dose naloxone does not improve cerebral or myocardial blood flow during
      cardiopulmonary resuscitation in pigs.
AB  - In a prospective, randomized, placebo-controlled, double-blind trial we tested
      the hypothesis that naloxone given during cardiopulmonary resuscitation (CPR)
      enhances cerebral and myocardial blood flow. Twenty-one anesthetized,
      normoventilated pigs were instrumented for measurements of right atrial and
      aortic pressures, and regional organ blood flow (radiolabeled microspheres).
      After 5 min of untreated fibrillatory arrest, CPR was commenced using a pneumatic
      chest compressor/ventilator. With onset of CPR, an i.v. bolus of 40 micrograms/kg
      b.w. of epinephrine was given, followed by an infusion of 0.4 micrograms/kg per
      min. After 5 min of CPR, either naloxone, 10 mg/kg b.w. (group N, n = 11) or
      normal saline (group S, n = 10) was given i.v. Prior to, and after 1, 15, and 30
      min of CPR, hemodynamic and blood flow measurements were obtained. After 30 min
      of CPR, mean arterial pressure was significantly higher in group N (26 +/- 5 vs.
      13 +/- 3 mmHg, P < 0.05). Groups did not differ with respect to myocardial
      perfusion pressure or arterial blood gases at any time during the observation
      period. Regional brain and heart blood flows were not different between N and S
      at any point of measurement. We conclude that high-dose naloxone does not augment
      cerebral or myocardial blood flow during prolonged closed-chest CPR.

PMID- 9178389
TI  - Effects of manual high-impulse CPR on myocardial perfusion during cardiac arrest
      in pigs.
AB  - The aim of the study was to compare the effect of a 30 and 50% duty cycle on
      coronary perfusion pressure (CPP) and end tidal carbon dioxide (ETCO2) and to
      determine whether a duty cycle of 30% can be achieved manually. After 3 min of
      ventricular fibrillation cardiac arrest, pigs were resuscitated in two groups
      with changing duty cycles every 3 min: group A starting with 50 and then 30%; and
      group B starting with 30 and then 50%. After administration of epinephrine, duty
      cycles in group A were 50 and then 30%, in group B initially 30% and then 50%
      Before administration of epinephrine, no significant differences in CPP between
      the 30 and 50% duty cycles were found; after epinephrine CPP increased with both
      duty cycles. ETCO2 did not vary before epinephrine; after epinephrine, there were
      statistically significant differences but there is doubt regarding the clinical
      relevance of these differences. Survival was 4/6 in group A and 3/5 in group B
      (NS). It is possible to perform a manual duty cycle of 30%. However, our data do
      not support the use of a 30% duty cycle during cardiopulmonary resuscitation
      (CPR).

PMID- 9178390
TI  - Future directions for resuscitation research. V. Ultra-advanced life support.
AB  - Standard external cardiopulmonary resuscitation (SECPR) frequently produces very
      low perfusion pressures, which are inadequate to achieve restoration of
      spontaneous circulation (ROSC) and intact survival, particularly when the heart
      is diseased. Ultra-advanced life support (UALS) techniques may allow support of
      vital organ systems until either the heart recovers or cardiac repair or
      replacement is performed. Closed-chest emergency cardiopulmonary bypass (CPB)
      provides control of blood flow, pressure, composition and temperature, but has so
      far been applied relatively late. This additional low-flow time may preclude
      conscious survival. An easy, quick method for vessel access and a small preprimed
      system that could be taken into the field are needed. Open-chest CPR (OCCPR) is
      physiologically superior to SECPR, but has also been initiated too late in prior
      studies. Its application in the field has recently proven feasible. Variations of
      OCCPR, which deserve clinical trials inside and outside hospitals, include
      'minimally invasive direct cardiac massage' (MIDCM), using a pocket-size plunger
      like device inserted via a small incision and 'direct mechanical ventricular
      actuation' (DMVA), using a machine that pneumatically drives a cup placed around
      the heart. Other novel UALS approaches for further research include the use of an
      aortic balloon catheter to improve coronary and cerebral blood flow during SECPR,
      aortic flush techniques and a double-balloon aortic catheter that could allow
      separate perfusion (and cooling) of the heart, brain and viscera for optimal
      resuscitation of each. Decision-making, initiation of UALS methods and diagnostic
      evaluations must be rapid to maximize the potential for ROSC and facilitate
      decision-making regarding long-term circulatory support versus withdrawal of life
      support for hopeless cases. Research and development of UALS techniques needs to
      be coordinated with cerebral resuscitation research.

PMID- 9178391
TI  - Optimizing the treatment of Paget's disease of bone.

PMID- 9178392
TI  - Nucleosomes and lupus.

PMID- 9178393
TI  - Arthroscopy-assisted synovectomy in the treatment of chronic synovitis of the
      knee.
AB  - The place of arthroscopy-assisted synovectomy in the treatment of inflammatory
      synovitis of the knee was evaluated by studying 26 patients who underwent this
      procedure between November 1992 and September 1995. Half the patients had
      rheumatoid arthritis. Twenty-three patients (28 knees) were reevaluated after a
      mean follow-up of 32 months (range, 4-50 months). The arthroscopic synovectomy
      was done either as the first-line synovectomy procedure, after failure of
      triamcinolone hexacetonide injection into the joint, or as the second-line
      synovectomy procedure, after failure of osmic acid or yttrium-90 synovectomy.
      Except in one patient with severe arthritis, arthroscopic synovectomy produced
      statistically significant improvements regarding pain (visual scale), function
      (Lequesne's index), range of flexion, amount of joint fluid and knee
      circumference. The range of extension of the knee was normal at baseline and
      remained so after the procedure. Overall efficacy was similar for first-line and
      second-line procedures. Results were rated good to very good by 71% of the
      patients and 61% of the physicians overall and the overall improvement in knee
      arthritis as perceived by the patients was 60%. The procedure was well tolerated
      in 93% of cases. The mean time needed to achieve a stable improvement was 3.2
      weeks for pain, 4.7 weeks for swelling and 3.6 weeks for range of motion. One
      case each of hemarthrosis and stiffness of the knee were recorded, with a full
      recovery in both cases. Arthroscopic synovectomy is effective and safe but more
      burdensome and expensive than osmic acid or radiation synovectomy, and
      consequently deserves a place of choice in patients who have failed to respond to
      either of the last two methods.

PMID- 9178395
TI  - Polyostotic Paget's disease. A search for lesions of different durations and for
      new lesions.
AB  - We conducted a medical record-based study of 169 patients with polyostotic
      involvement identified among 200 Paget's disease patients. Follow-up was 15 to 41
      years in 31 cases. The pelvis was the only bone that was more likely than not to
      be involved bilaterally. All the other paired bones were more likely to be
      involved unilaterally and when both sides were involved the two lesions were very
      often frankly asymmetric. In a given patient, the duration of the various pagetic
      lesions, estimated from their size and from data provided by an earlier study on
      the rate of progression of pagetic lesions, was similar in some cases and showed
      marked differences in others. Aggregation of the lesions into two or three
      disease duration groups was seen in some patients, suggesting that Paget's
      disease may occur in two or three waves. When we reviewed the radiographs from 30
      patients with a mean follow-up of 23 years, we found new lesions in ten patients.
      However, a review of bone scans from 18 patients with a mean follow-up of 11
      years failed to uncover any firm evidence of new lesion development, perhaps
      because all these patients received bisphosphonate therapy (etidronate,
      tiludronate, pamidronate). We also found data suggesting that the disease process
      spread across a joint in some patients, even in the absence of degenerative joint
      disease. In particular, in several cases an extensive pagetic lesion was seen on
      one side of a joint and a considerably smaller lesion on the other side.

PMID- 9178394
TI  - Inflammatory joint disease after immunizations. A report of two cases.
AB  - Serious adverse effects of immunizations are uncommon. The hepatitis B vaccine
      has been implicated in a few dozen cases of extraarticular, systemic, or
      inflammatory joint disorders. We report two cases in which hepatitis A
      vaccination (Havrix, Smith Kline Beecham) was followed by a connective tissue
      disorder or a spondylarthropathy in two healthy males aged 50 and 24 years,
      respectively. Both patients were HLA B27-negative but carried the HLA DR1 and/or
      DR4 antigen. The outcome was favorable after treatment with a corticosteroid or a
      nonsteroidal antiinflammatory agent. The pathophysiology of immunization-related
      rheumatic disorders may involve circulating immune complexes and/or a mechanism
      similar to that seen in reactive arthritis, i.e., a genetically-determined
      susceptibility to the bacterial or viral antigens contained in vaccines.

PMID- 9178396
TI  - Hip axis length measurement using dual-energy X-ray absorptiometry.
AB  - Hip axis length (HAL) has been reported, in the United States, to influence the
      risk of hip fractures independently from age and proximal femoral bone mineral
      density. Last-generation dual-energy X-ray absorptiometry units can perform
      automatic hip axis length measurements. The present study was designed to
      evaluate the feasibility of this measurement in clinical practice and to
      establish the range of normal values obtained in French women using single- and
      fan-beam absorptiometry. Short-term reproducibility determined by performing two
      measurements with repositioning in 50 women was 1.67%. Long-term reproducibility
      calculated based on five measurements taken at six-month intervals in 60 women
      was 1.5%. No statistically significant differences were found between hip axis
      length on the right and left sides in 50 women. Mean values calculated based on
      measurements in 190 women aged 54 +/- 12 years (single-beam absorptiometry) and
      in 50 women aged 80 +/- 5 years (fan-beam absorptiometry) were 10.4 +/- 0.6 cm
      and 11.5 +/- 0.7 cm, respectively. Hip axis length was correlated with height but
      not with age or femoral neck bone mineral density. Our data are consistent with
      studies conducted in the United States. The interpretation of hip axis length
      measurements requires knowledge of the type of X-ray beam used (single or fan
      shaped). Whether hip axis length predicts the hip fracture risk in Europeans
      remains to be demonstrated.

PMID- 9178397
TI  - Bone mineral density in patients given oral vitamin K antagonists.
AB  - BACKGROUND: Divergent results have been obtained in studies of bone mineral
      density in patients under oral vitamin K antagonists. OBJECTIVE: To gather
      prospective data on bone mineral density and bone metabolism in 70 aortic valve
      replacement patients. STUDY DESIGN: 49 patients who had been under oral vitamin K
      antagonists for at least one year after implantation of a mechanical aortic valve
      were compared with 21 recipients of a tissue aortic valve that did not require
      anticoagulant therapy. The following investigations were done in all patients:
      (1) dual-energy X-ray absorptiometry measurement of bone mineral density at the
      lumbar spine and femoral neck; (2) roentgenograms of the spine and pelvis; (3)
      serum assays of calcium, phosphate, creatinine, alkaline phosphatase,
      osteocalcin, 25-OH-vitamin D3, and parathyroid hormone. RESULTS: The two groups
      were comparable regarding age and sex ratio. No differences were found in lumbar
      or femoral neck bone mineral density even after adjustment for age and sex. A
      trend toward an increase in bone mineral density at both sites with increasing
      duration of vitamin K antagonist therapy was demonstrated. The only bone turnover
      marker difference between the two groups was a significantly lower serum
      osteocalcin level in the group under vitamin K antagonist therapy (P < 0.0001).
      CONCLUSIONS: Long-term vitamin K antagonist therapy does not affect bone mineral
      density at the lumbar spine or femoral neck and also fails to modify bone
      turnover markers, with the exception of osteocalcin.

PMID- 9178398
TI  - The pathophysiology of uveitis.

PMID- 9178399
TI  - Efficacy of misoprostol in the prophylaxis of gastroduodenal lesions induced by
      short-term nonsteroidal antiinflammatory drug therapy in elderly patients. A
      multicenter double-blind, placebo-controlled trial.
AB  - Advanced age is an established risk factor for gastrointestinal toxicity of
      nonsteroidal antiinflammatory drugs, and the duration of use of these agents in
      elderly patients should be kept as short as possible. A multicenter, double
      blind, placebo-controlled trial was conducted to evaluate the efficacy of
      misoprostol in preventing gastrointestinal toxicity in elderly patients (> or =
      65 years) given nonsteroidal antiinflammatory agents for no more than ten days.
      Patients who were to receive a nonsteroidal antiinflammatory agent for ten days
      to treat an acute rheumatic condition were randomly allocated to treatment with
      either a placebo or misoprostol in a dose of 200 micrograms bid. The primary
      efficacy criterion was the result of a gastroduodenal endoscopic evaluation done
      on day 10. The outcome of the rheumatic condition, changes in serum creatinine
      levels, and clinical safety were also evaluated. The study population included
      208 subjects with a mean age of 81.4 +/- 6.4 years, of whom 81.3% were women. The
      misoprostol group (n = 104) and the placebo group (n = 104) were comparable at
      baseline. The incidence of endoscopically visible gastric lesions after ten days
      of nonsteroidal antiinflammatory drug therapy was significantly lower in the
      misoprostol group (25%) than in the placebo group (43%) (P = 0.001). In contrast,
      no statistically significant difference was found for the incidence of duodenal
      lesions between the two groups. The incidence of gastroduodenal ulcers was
      significantly lower (P < 0.021) in the misoprostol group (4.1%) than in the
      placebo group (13.5%). Changes in serum creatinine levels on day 10 versus
      baseline were similar in the two groups. The nonsteroidal antiinflammatory drug
      was well tolerated clinically when given alone or in combination with
      misoprostol.

PMID- 9178401
TI  - A new case of insufficiency fracture in a patient with tabes dorsalis.
AB  - A new case of insufficiency fracture in a patient with tabes dorsalis is
      reported. Whereas the osteoarthropathies and bone lesions due to tabes dorsalis
      are well known, only one other case responsible for bone loss has been reported
      in the medical literature.

PMID- 9178400
TI  - Osteoporotic vertebral fractures in a man under high-dose inhaled glucocorticoid
      therapy. A case-report with a review of the literature.
AB  - A 65-year-old man had surgery in June 1995 for femoral neuralgia. The plain films
      of the spine were normal at the time. In September of the same year, when he was
      beginning to walk gradually longer distances, he started experiencing back pain.
      Crush fractures of T8 and L2 were seen on plain films. His pain worsened, and he
      was admitted in December 1995. A third set of plain films disclosed fractures of
      all the vertebral bodies from T8 through L5, with increased density of the
      endplates of the same vertebras. Serum and urinary levels of calcium and
      phosphate were normal. Dual-energy X-ray absorptiometry demonstrated osteoporosis
      predominating in the trabecular bone. Evidence of increased bone resorption was
      seen on the histomorphometric study. Large amounts of dihydroxypyridinoline were
      found in the urine. Investigations for the classical causes of osteoporosis in
      males were unrewarding. Careful questioning revealed that the patient had been
      taking inhaled beclomethasone for seven years to treat chronic obstructive lung
      disease. Serum levels of cortisol and ACTH were low, consistent with a diagnosis
      of treatment-induced hypercorticism. To our knowledge, this is the first reported
      case of osteoporotic vertebral fractures in a male due to inhaled glucocorticoid
      therapy. Inhaled glucocorticoids are generally believed to induce only minimal
      systemic effects. However, decreased serum osteocalcin levels and increased
      urinary excretion of bone resorption markers have been reported in patients under
      inhaled beclomethasone therapy. Low spinal bone mineral density values correlated
      with the degree of pituitary-adrenal gland suppression as evaluated using the
      ACTH test have also been found in several groups of patients treated with inhaled
      glucocorticoids.

PMID- 9178402
TI  - Multifocal malignant fibrous histiocytoma of the spine.
AB  - A 40-year-old patient was seen because of a three-month history of low back pain
      unresponsive to standard therapy. Crush fractures of T12 and L2 were seen on
      plain radiographs. A magnetic resonance imaging study disclosed lesions of all
      the vertebral bodies from T12 to the sacrum sparing the disks and epidural space.
      Histologic features of a vertebral biopsy specimen was consistent with malignant
      fibrous histiocytoma of the bone. The multifocal distribution caused some
      reluctance to accept this diagnosis, which was, however, confirmed by detailed
      immunohistochemical studies and reevaluation of the histologic slides by
      independent observers who were unaware of the initial diagnosis. Chemotherapy
      with doxorubicin and cisplatin was started but the patient died 15 months after
      the diagnosis. Malignant fibrous histiocytoma mainly affects the metaphyses of
      the long tubular bones. The spine is a very uncommon site of localization of this
      tumor. The multifocal spinal lesions in our patient may have been produced by
      metastases from an unidentified primary or by direct spread via the perivertebral
      soft tissues of a primary located in a vertebral body. The management of
      malignant fibrous histiocytoma relies on a combination of surgery and
      chemotherapy. Although complete excision of the tumor can be followed by
      prolonged survival, the prognosis is bleak in unresectable forms.

PMID- 9178403
TI  - Acute sacroiliac arthritis and sarcoidosis.

PMID- 9178404
TI  - Destructive gouty arthritis of the hip.

PMID- 9178405
TI  - The prevalence of Paget's disease in 1994 in a rheumatology department of a Paris
      hospital.

PMID- 9178406
TI  - Patients' acceptance of waiting for cataract surgery: what makes a wait too long?
AB  - The patient's perspective about waiting for elective surgery is an important
      consideration in the management of waiting lists, yet it has received little
      attention to date. This study was undertaken to assess the acceptability of
      personal waiting times from the perspective of patients, and to examine waiting
      time and patient characteristics associated with the perception that a wait for
      cataract surgery is too long. The international prospective study was conducted
      in three sites with explicit waiting systems: Manitoba, Canada; Denmark; and
      Barcelona, Spain. Patients over the age of 50 years were recruited consecutively
      from ophthalmologists' practices at the time of their enlistment for first-eye
      cataract surgery. Anticipated waiting time, opinions about personal waiting time,
      and patients' visual and health characteristics were identified by means of
      telephone interviews. The 550 patients interviewed at the time of enlistment for
      surgery anticipated waits varying from < 1 to 24 months. Clinical visual acuity
      measures were obtained from patients' ophthalmologists/cataract surgeons. Results
      indicated that anticipated waiting time was the strongest predictor of patients'
      tolerance of waiting for cataract surgery. Patient dissatisfaction increased with
      the duration of the anticipated wait. Patients in all three sites were accepting
      of waits of three months or less, and considered waits exceeding six months to be
      excessive. Response to waits between three and six months varied across study
      sites. Patients with low tolerance for waiting had greater self-reported
      difficulty with vision, as assessed by a Cataract Symptom Score and expressed
      trouble with vision. Patients' acceptance of waiting was not associated with
      clinical visual acuity measures or socio-demographic characteristics. The patient
      perspective on acceptability of waiting times for cataract surgery suggests that
      restricting waiting times to less than six months and preferably less than three
      months and utilizing self-reported measures of visual difficulty in prioritizing
      patients may contribute to improved management of waiting systems. Patients are
      more tolerant of their personal waiting times than responses to questions about
      waiting for elective surgery in general would indicate, and appear to accept
      waiting times that are longer than those identified as reasonable by specialists.

PMID- 9178407
TI  - Meanings in policy: a textual analysis of Canada's "Achieving Health For All"
      document.
AB  - This paper presents a textual analysis of a key Canadian health policy document-
      Achieving Health for All (AHFA). It begins by establishing the importance of
      policy language and an interpretive approach to reveal dominant meanings and
      assumptions. This approach points out the significance of language and its
      contexts (text and intertext) and of developing a formal analytic strategy, based
      on semiotics. The paper concludes with a detailed, illustrated analysis of AHFA,
      suggesting that the document's discourse, through appealing to all, with emphases
      on the nation, community and all Canadians, establishes a frame of individual
      responsibility and rights, health promotion and broad health determinants--a
      frame that resonates with the cost-constrained nature of health care delivery-as
      found in provincial reform documents in the 1980s and 1990s.

PMID- 9178408
TI  - Health status and risk factors of seminomadic pastoralists in Mongolia: a
      geographical approach.
AB  - The particular lifestyle of nomadic or seminomadic people has much to do with
      their health status. This discussion of the conceptual basis and some preliminary
      results of the 1992-94 health status and risk factor survey in Mongolia serves to
      highlight some of the relationships existing between the general health status
      and potential risk factors observed among pastoral nomads. In addition to graphic
      description of the data, a statistical analysis suggests significant associations
      between certain health status indicators and gender, location, lifestyle factors
      (e.g. smoking) socio-economic status, preventive health care and the physical
      environment. With regard to locational factors, there are strong regional
      differences in a wide-ranging number of health status indicators. The results of
      this study, obtained as they were at the threshold of Mongolia's economic and
      political transformation, will serve as a baseline against which to evaluate
      future changes in the health of Mongolians.

PMID- 9178410
TI  - Community and self: concepts for rural physician integration and retention.
AB  - Low physician availability in rural areas of the United States is a long-standing
      issue. While most research has focused upon the locational decisions of
      physicians to understand the causes of the problem, a relatively new and
      neglected research focus is the retention of rural physicians. This paper takes
      the perspective that integration of physicians within rural communities is the
      basis for retention. It introduces concepts of self and community as a basis for
      understanding "domains" of rural physician integration. From data collected
      during in-depth qualitative research in rural Kentucky, a framework of
      integration domains is developed. The three domains of physician self, medical
      community, and community-at-large are elaborated with examples from the data. To
      further explain the relationships among the integration domains and their value,
      the findings are combined with three concepts from social theory. Social capital,
      core participation, and community reconstruction add dynamic and meaningful
      aspects to the context in which integration and retention occur, and they provide
      a conceptual basis to use when investigating or devising actions to facilitate
      integration.

PMID- 9178409
TI  - Urban ecological structure and perceived child and adolescent psychological
      disorder.
AB  - This research examined the distribution and ecological correlates of referrals of
      children and adolescents to the Regional Children's Centre, a psychological
      assessment and treatment centre located in Windsor, Ontario, Canada. Referral
      data were collected by the Regional Children's Centre for the study period April
      1992 through March 1994. The ecological structure of the study area was derived
      using principal components analysis of a set of socio-economic indicator
      variables from the 1991 Census of Canada and a cluster analysis of component
      scores. Referral rates were calculated for each ecological area for two referral
      subgroups; modi/conduct/stress-related concerns and neurophysiologically based
      concerns. The distribution of referrals was tested using the Poisson probability
      test. This test revealed that, for both subgroups analysed, the distribution of
      referrals in the study area was non-random. Stepwise multiple regression revealed
      a significant ecological relationship between the mood/conduct/stress-related
      concerns referral rate and the ecological structure of the study area. No such
      relationship was found, however, when examining referrals for
      neurophysiologically based concerns.

PMID- 9178411
TI  - Intra-household allocation of food and health care: current findings and
      understandings--introduction.
AB  - This work offers an anthropological analysis of intra-household processes
      underlying gender- and age-specific differences in individual nutritional and
      health care allocations and outcomes in particular cultures. Based on recent
      ethnographic studies in India, Nepal, Madagascar, Mexico, and Peru,
      correspondences are analyzed between local cultural ("emic") and scientist-policy
      maker practitioner ("etic") understandings of nutrition, health, and human
      development, and the relative "values" of females, males, and children of
      different ages. The data and analyses clarify specific epidemiological and
      demographic findings on age and gender bias in nutrition and health and highlight
      the multiple cultural, economic, and biological factors that contribute to gender
      or age-based discrimination or neglect. Recent advances in nutrition policy have
      argued for a broader concept of nutritional security, one that incorporates both
      food quantity and quality, and of nutrition as "food, health and care"
      (International Conference on Nutrition, World Declaration and Plan of Action for
      Nutrition, FAO/WHO, Rome, 1992). These ethnographic findings; lend strong support
      for such broader nutrition concepts and associated nutrition policies. The
      studies also suggest ways in which anthropological questions, methods, and data
      and community-based research can help predict or identify the nutritionally
      vulnerable within households and help other social and medical scientists design
      more effective interventions.

PMID- 9178412
TI  - Social class, gender and intrahousehold food allocations to children in South
      Asia.
AB  - In the 1980s research on gender-biased food distribution to children within the
      household in South Asia yielded important findings. Many studies report evidence
      of substantial discrimination against daughters, but others do not. This paper
      reviews research of the 1980s with attention to social differentiation in gender
      bias. My hypothesis is that different results concerning gender bias in
      intrahousehold allocations are expectable, given variations in gender hierarchy
      throughout South Asia. Results of the review indicate that seemingly
      "contradictory" results are often accurate reflections of social status
      differences within South Asia that create varying female health and nutritional
      outcomes.

PMID- 9178413
TI  - Food allocation in rural Peruvian households: concepts and behavior regarding
      children.
AB  - Intrahousehold food allocation is an important determinant of child health and
      survival. In this paper I explore the ways in which food is distributed to young
      children in Ura Ayllu, a farming community located in the southern Peruvian
      highlands (Province of Sandia, Department of Puno, Peru). Quantitative data on
      energy intake and growth status are analyzed for two groups of children: toddlers
      (one through three years) and preschoolers (four through six years). The analyses
      indicate no gender differences in energy intake or growth among toddlers (one
      through three years) and preschoolers (four through six years) and that young
      children do not appear to be deprived of food relative to older household
      members, especially adults. Relative to standards specific to Andean populations,
      the mean caloric content of the toddler diet falls slightly below the estimated
      requirement for the age group while the preschooler diet is found to be
      calorically adequate. This paper also examines the ideological bases that shape
      food allocation within households. Regarding the local concepts and cultural
      rules that guide food allocation to children, Ura Ayllinos view young children as
      developmentally immature and believe their dietary and health needs are different
      from those of older children and adults. Infants and young children are
      considered weak (debil) and vulnerable to illness. Parents state that young
      children should not feel hunger which is thought to weaken a person and make him
      more susceptible to the natural and supernatural agents that cause illness.
      Certain dietary practices, such as on-demand breastfeeding and snacking between
      meals, suggest that parents try to avoid the experience of hunger and the
      potential for illness by making food available to their children. This study
      suggests that young Ura Ayllu children are viewed as having a right to food based
      on local concepts of child development, personhood, and general health
      maintenance.

PMID- 9178414
TI  - Health care allocation and selective neglect in rural Peru.
AB  - This study of health care allocation to children in northern Puno, Peru, utilizes
      quantitative and qualitative data to explore differential resource allocation to
      children in rural Andean households. As part of a broader ethnographic study of
      health in two communities, quantitative data on reported health status, symptoms,
      and treatments (both lay and specialist) were collected for 23 children under the
      age of 7 over a one year period. Additional data were collected from local health
      post records. Data were analyzed by gender, and by three age groups (birth to 1
      year, 1-3 years, 4-6 years) to determine if differences existed in the allocation
      of health care. The data suggest a pattern of discrimination against females and
      younger children, especially infants under age one, despite the fact that these
      groups were reported to be sicker. Differences were especially significant in the
      allocation of biomedical treatments, the most costly in terms of parental time,
      effort, and money. Ethnographic data on child illness, gender, and developmental
      concepts help to explain why children of different genders and ages may be
      treated differently in the rural andes. They provide a context in which to
      interpret health care allocation data, and, in the absence of a population-based
      study, reinforce findings based on the limited study sample. Female children are
      valued less because of their future social and economic potential. Females are
      also regarded to be less vulnerable to illness than male children, meaning that
      less elaborate measures are necessary to protect their health. Young children are
      thought to have a loose body-soul connection, making them more vulnerable to
      illness, and are though to be less human than older individuals. The folk
      illnesses urana (fright) and larpa explain child deaths in culturally acceptable
      ways, and the types of funerals given to children of different ages indicate that
      the death of young children is not considered unusual. Health care allocation and
      ethnographic data suggest that selective neglect (passive infanticide) may be
      occurring in rural Peru, possibly as a means of regulating family size and sex
      ratio. It is important to go beyond placing blame on individual parents or on
      culture, however, to address the underlying causes of differential health care
      allocation, such as poor socioeconomic conditions, lack of access to
      contraceptives, and female subordination.

PMID- 9178415
TI  - Why are boys so small? Child growth, diet and gender near Ranomafana, Madagascar.
AB  - Dietary and anthropometric data are analyzed by age, sex and household
      demographic structure for cultivators' children near Ranomafana National Park in
      the southeastern rain forest of Madagascar. The 1989 dry season cross-sectional
      survey of 613 0-9 year olds in seven communities identifies chronic dietary and
      growth deficits. In the 1989 sample, 62.2% of the children are below -2 s.d.
      height/age, while 9.4% are below -2 s.d. wright/height of the NCHS international
      standard. The 1990-1991 dry and wet season study of 40 and 39 6-9 year olds and
      their households in two adjacent hamlets provides further detail about
      intrahousehold dietary practices. Overall, weight/height status is worse during
      the wet season. Male anthropometric status is worse than that of females during
      the dry season, but shows less seasonal variation. The male dietary intake is
      similar to or sometimes less adequate than female dietary intake in the different
      age cohorts. Data are also analyzed by single- and multiple-parent households
      where children make different contributions to the socioeconomic needs. Older
      girls in single-parent households have increased workloads and dietary intake
      compared with their siblings or age-mates.

PMID- 9178416
TI  - Cultural factors, caloric intake and micronutrient sufficiency in rural Nepali
      households.
AB  - This study examined the allocation of food within 105 Nepali households using a
      combination of recall and observation methods. While a relationship exists
      between caloric intake and sufficiency of intake of several key micronutrients
      (i.e., beta carotene, vitamin C and iron) for the study population as a whole
      this relationship is weaker for certain subgroups. In particular, micronutrient
      intakes of adolescent girls and adult women are much less likely to be tried to
      total caloric consumption when compared with the intakes of other household
      members. This gender differential appears linked in part to specific food beliefs
      and practices that tend to reduce women's consumption of micronutrient-rich
      foods, such as dietary restrictions during menstruation, pregnancy and lactation.
      Overlapping with these beliefs and practices, an overall pattern of disfavoritism
      of females in the intrahousehold allocation of food is evident in the study
      communities. While staple food items (i.e. rice, lentil soup, bread, etc.) are
      distributed fairly equally, side dishes usually containing a higher proportion of
      micronutrients (i.e. vegetables, meat, yogurt, ghee, etc.) are often
      preferentially allocated to valued household members, including adult males and
      small children (of both sexes).

PMID- 9178417
TI  - Examining the gender gap in nutrition: an example from rural Mexico.
AB  - Gender differences in nutrient and food intake were examined in Mexican Nutrition
      CRSP (Collaborative Research Support Program) infants (N = 75), preschoolers (N =
      80), and school children (N = 91). No significant gender differences in dietary
      quality or quantity were seen for infants and preschoolers. For school children,
      the contribution of various foods to total energy intake (dietary quality) was
      also quite similar for girls and boys. Equity in dietary quality remained even
      under conditions of economic and demographic stress. Nevertheless, school girls
      consumed significantly less energy per day than boys (-300 kcal/d or 1.3 mJ/d),
      and less of all micronutrients examined. Gender differences in estimated basal
      metabolic rates of school children were slight (-20 kcal/d), and body composition
      and size were similar. When energy intakes were expressed as a percent of
      estimated requirement (calculated from age, sex and weight using WHO/FAO/UNU
      equations), intakes were adequate and not significantly different between girls
      (mean = 111%) and boys (mean = 113%). Playground observations showed girls to be
      less active than boys, which may reflect both cultural and biological influences.
      Apparently due to this lower activity, school girls consumed less energy, and may
      have been at much higher risk than boys of micronutrient deficiency. The lower
      food intakes of girls did not appear to be due to purposeful dietary
      discrimination, but rather to culturally patterned sex roles involving lower
      activity.

PMID- 9178418
TI  - Physician location survey: self-reported and census-defined rural/urban
      locations.
AB  - Using a survey of New York State Residence-Trained Family Physicians and the 1990
      census data, this paper assesses the relative importance and consistency of
      factors associated with physician practice locations when different definitions
      of community size are used. By matching the zip code information with 434
      physicians' practice locations, physician respondents' self-reported communities
      are linked to census-defined communities. It was found that the significant level
      of some variables could be affected when community classifications were based on
      survey responses rather than census data. It concludes that caution should be
      taken for interpreting rural-urban differences when data are solely based on self
      reported practice locations.

PMID- 9178419
TI  - Multiple-quantum magic-angle spinning and dynamic-angle spinning NMR spectroscopy
      of quadrupolar nuclei.
AB  - Several aspects of the Multiple-Quantum Magic-Angle Spinning (MQMAS) technique
      (L. Frydman and J.S. Harwood, J. Am. Chem. Soc., 117 (1995) 5367) are compared
      with Dynamic-Angle Spinning (DAS). Examples of MQMAS spectra are shown for I =
      3/2 nuclei with CQ up to 3.6 MHz, and for 27Al (I = 5/2) with CQ up to 10 MHz.
      The MQMAS linewidth is largely independent of the magnitude of the homonuclear
      dipolar interaction, while the spinning sideband manifold is similar to that
      observed in DAS experiments. MQMAS is technically simple and routinely useful for
      studying nuclei with short spin-lattice relaxation times, but care must be taken
      in its use for quantitative studies as the excitation of the triple-quantum
      coherence is not uniform. In this regard, MQMAS is most useful for samples with
      small quadrupolar coupling constants. In the specific case of 17O, DAS would give
      spectra with excellent resolution in comparison to MQMAS. The different
      advantages of DAS and MQMAS make them useful complementary techniques in many
      cases. Two additional methods are also presented for extracting the chemical
      shift anisotropy (CSA) directly for quadrupolar nuclei using the multiple-quantum
      scheme.

PMID- 9178420
TI  - Multiple-pulse assisted line-narrowing by fast magic-angle spinning.
AB  - Combined rotation and multiple-pulse experiments (CRAMPS) are reported that are
      performed under the conditions of fast magic-angle spinning. Quasi-static
      conditions, as are required for CRAMPS experiments, can be fulfilled
      approximately also for fast sample spinning conditions when windowless or
      semiwindowless sequences are applied. In order to allow direct detection for
      these cases also, appropriately timed detection windows are introduced without
      loss of resolution. In contrast to conventional CRAMPS experiments, high-speed
      MAS was found to play an important role also in the averaging of residual dipolar
      contributions. The resolution achieved in these first experiments is comparable
      to that of conventional CRAMPS experiments and the demands with respect to
      spectrometer hardware and tuning are much lower.

PMID- 9178421
TI  - Two-dimensional spin-exchange solid-state NMR studies of 13 C-enriched wood.
AB  - Two-dimensional high-resolution solid-state NMR has been used to study 13C
      enriched wood. Wood is a complex material containing three major polymers:
      cellulose, hemicelluloses and lignin. The use of an enriched 13C-compound allows
      the observation of intra-molecular spin-diffusion driven by dipolar couplings.
      Correlations between spins at progressively longer distances have been obtained
      as the mixing time is increased, corresponding, for each of the separate polymer
      chains, to intra-unit and then to inter-unit interactions, and in the case of
      cellulose to inter-chain interactions. A straightforward qualitative analysis of
      the spin diffusion spectra is shown to yield the assignment of the carbon-13
      spectrum. The cellulose resonances can all be sequentially assigned using the
      spin diffusion experiment. Using the experiments it is shown that, at least on a
      distance scale of several nanometres explored by the spin diffusion process, the
      three main components of wood occur in separate phases. Also, a question
      concerning the structure of the hemicellulose units is resolved by locating the O
      acetyl group at the 2-position of the xylan chains.

PMID- 9178422
TI  - 51V magic-angle-spinning NMR and electric field gradient calculations in V2O5 and
      gamma-LiV2O5 crystals.
AB  - 51V Magic-angle-spinning (MAS) NMR has been applied to V2O5 at two different
      magnetic field strengths (4.7 and 7.1 T). Both the magnitude and relative
      orientation of the quadrupole and chemical shift (CS) tensors have been
      determined by iterative fitting of the 51V MAS NMR lineshapes at the two magnetic
      field strengths. The reliability of the results is discussed. Moreover, it is
      shown that previous low-field single-crystal data are fully consistent with the
      high-field powder-sample MAS NMR results provided that a slight noncoincidence
      between the CS tensor and the crystal frame axes is considered. The electric
      field gradient tensor at the vanadium and lithium sites is subsequently used to
      test several electronic structure calculation at an ab initio Hartree-Fock level
      in V2O5 and gamma-LiV2O5 crystals. It is shown that a wide distribution of oxygen
      charges must be considered to describe the particular environment of each type of
      oxygen atoms. Furthermore, this analysis supports the fact that the vanadyl bond
      is likely a short ionic bond. NMR is found to be a valuable experimental tool to
      get insight into the nature of chemical bonds in vanadium oxides.

PMID- 9178423
TI  - Effects of finite pulse width on free induction decay.
AB  - The shape of the free induction decay for the case in which the amplitude B1 (B1
      = omega 1/gamma) of the RF pulse is comparable with local magnetic fields at
      sites of the nuclei is considered. It is shown that the shape of the FID G(t +
      tau) (where tau is the width of a RF pulse, t is the time after a RF pulse)
      depends on the shape of the FID G0(t) following a hard, delta function RF pulse
      and on the shape of the function F0(tau), which describes the evolution of the
      longitudinal nuclear magnetization Mz under the effect of the hamiltonian (H0
      omega 1 I gamma), where H0 is the interaction hamiltonian of the nuclear spin
      system. Calculations of F0(tau) and G(t + tau) for different interaction
      hamiltonians H0 are presented.

PMID- 9178424
TI  - Phospholipid headgroup dynamics in DOPG-d5-cytochrome c complexes as revealed by
      2H and 31P NMR: the effects of a peripheral protein on collective lipid
      fluctuations.
AB  - The dynamics of the glycerol headgroup of dioleoylphosphatidylglycerol (DOPG) in
      hydrated bilayers were studied by 2H and 31P NMR spectroscopy, and the effects of
      binding a peripheral protein, cytochrome c, were evaluated. The fast headgroup
      segmental motions (tau c, 10(-10)-(-13) s) of DOPG in fully hydrated bilayers
      were not affected upon binding of cytochrome c, as evaluated by the spin-lattice
      (T1) relaxation of deuterons in the DOPG glycerol headgroup. In contrast, the
      spin-spin (T2e) relaxation is strongly affected, indicating that slow cooperative
      bilayer motions (tau c, 10(-3)-10(-6) s) are enhanced upon the interaction with
      cytochrome c, 2H and 31P NMR spectral lineshape analysis reveal details of the
      nature of these motions. The importance of these effects are discussed in terms
      of a possible mechanism for modulating membrane-associated processes.

PMID- 9178425
TI  - Synthesis of 13-ethyl-17-hydroxy-11-methylene-18, 19-dinor-17 alpha-pregn-4-en-20
      yn-3-one (3-oxo desogestrel).

PMID- 9178426
TI  - Synthesis and progestational activity of 16-methylene-17 alpha-hydroxy-19
      norpregn-4-ene-3,20-dione and its derivatives.
AB  - 16-Methylene-17 alpha-hydroxy-19-norpregn-4-ene-3,20-dione 1 and its 17 alpha
      acylated derivatives were synthesized. The length of the 17 alpha-side-chain
      ranges from C2-C6. As anticipated, compound 1 did not show any progestational
      activity or receptor binding activity; whereas, the acylated compounds,
      especially the butyrate, showed remarkable ability to bind to progesterone
      receptors. These compounds also showed progestational activity in an in vitro
      T47D cell culture assay in which progestins increase alkaline phosphatase
      activity and in an in vivo ovulation inhibition assay. All of the compounds
      synthesized were without estrogenic activities. The results showed that acylation
      of 16-methylene-17 alpha-hydroxy-19-norprogesterone can increase progestational
      activity. The progestational activities of these compounds varied with the 17
      alpha-side chain.

PMID- 9178427
TI  - 7 beta-hydroxy bile alcohols: facile synthesis and 2D 1H NMR studies of 5 beta
      cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol.
AB  - A rapid and easily performed procedure for the synthesis of 5 beta-cholestane-3
      alpha, 7 beta, 12 alpha, 25-tetrol by means of an efficient homologation sequence
      of the intermediate, 3 alpha, 7 beta, 12 alpha-triformyloxy-24-oxo-25-diazo-25
      homo-5 beta-cholane is described. The reaction sequence involved treating the
      intermediate, alpha-diazoketone in methanol with 3% AgNO3 or Ag2O, anhydrous
      Na2CO3, Na2S2O/H2O resulting in the formation of homoursocholic acid in high
      yield. Esterification of the homoursocholic acid in methanol containing a
      catalytic amount of methanesulfonic acid under microwave irradiation conditions
      gave methyl homourscholate. The subsequent treatment of methyl homoursocholate
      with methyl magnesium iodide provided 5 beta-cholestane-3 alpha, 7 beta, 12
      alpha, 25-tetrol in 88% yield. The products and synthetic intermediates prepared
      in these studies were fully characterized by the results of 1D and 2D NMR, and
      high-resolution mass spectral studies. These studies will help in further
      investigation of the defect of cholic acid biosynthesis in patients with
      cerebrotendinous xanthomatosis (CTX) as well as other inborn errors of bile acid
      metabolism.

PMID- 9178428
TI  - Synthesis of new delta 5-7-oxygenated and delta 5,7-unsaturated brassinosteroid
      analogs.
AB  - We report on the synthesis of the brassinosteroid analogs (22R,23R)-3 beta, 7
      beta, 22,23-tetrahydroxy-stigmast-5-ene (13), (22R,23R)-3 beta, 7 alpha, 22,23
      tetrahydroxy-stigmast-5-ene (15), and (22R,23R)-3 beta, 22,23-trihydroxy-stigmast
      5,7-diene (18) by means of the osmium-catalyzed asymmetric dihydroxylation of
      intermediate 1, available from stigmasterol. This reaction sequence produced the
      expected (22S,23S)- and (22R,23R)-triols 6 and 7 as well as the 22,23-diketo
      derivatives 2 and 3. The phytohormone activity of the new brassinosteroid analogs
      is discussed.

PMID- 9178429
TI  - The delta 5-3 beta-hydroxy steroid acyl transferase activities in tissues of the
      male rat and sheep.
AB  - Pregnenolone and dehydroepiandrosterone and their sulphate and fatty acid ester
      derivatives are concentrated in the mammalian brain, as compared to the
      peripheral organs. Although biological functions have been postulated for the
      free steroid and sulphate conjugates, the role of steroid fatty acid esters in
      the central nervous system (CNS) has yet to be established. A comparison of the
      esterifying capacities of brain and peripheral organs of the male rat and sheep
      is made here. The male rat brain was found to possess a higher esterifying
      capacity than all other tissues examined, with 5.32 +/- 2.46 pmol
      dehydroepiandrosterone fatty acid esters synthesized/mg protein/h and 1.89 +/-
      0.42 pmol pregnenolone fatty acid esters synthesized/mg protein/h. Sheep adrenal
      and sheep liver homogenates were found to have higher esterifying capacities than
      sheep brain. Within the brain of both species. delta 5-3 beta-hydroxy steroid
      acyl transferase enzyme(s) were concentrated in the microsomal fraction. The
      addition of a lecithin:cholesterol acyl transferase inhibitor to incubation
      assays resulted in a loss in enzyme activity. This effect was more significant in
      sheep brain microsomes than rat brain microsomes. It is likely that
      lecithin:cholesterol acyl transferase is more active in the sheep brain than the
      rat brain. Results from this study indicate that the steroid acyl transferase
      enzymes that are active in the mammalian brain are substrate specific.

PMID- 9178430
TI  - Hydroxysteroid sulfotransferase activity in the rat brain and liver as a function
      of age and sex.
AB  - The high concentrations of dehydroepiandrosterone sulfate and pregnenolone
      sulfate in the mammalian brain, despite the blood-brain barrier's impermeability
      to these compounds, and the apparent independence of these concentrations from
      those in plasma prompted us to investigate whether enzymatic sulfation of
      dehydroepiandrosterone was detectable in the rat brain. Low hydroxysteroid
      sulfotransferase activities were detectable in in vitro incubations of
      homogenates from all rat brain regions except the cerebellum, being highest in
      the hypothalamus and pons. This activity was not ascribable to enzyme in brain
      capillary blood. The activity was mainly cytosolic, although there was also
      significant activity in the partially purified nuclear fraction. The enzyme had
      different properties from those of hepatic isozymes, with a pH optimum of 6.5 and
      a high Km of approximately 2 mM for dehydroepiandrosterone. The enzyme was also
      active with pregnenolone as substrate. Activities in the brain were approximately
      300-fold lower than in the liver but, as in the liver, these were higher in
      females than in males. The variations in brain activity as a function of age did
      not parallel those in the liver. Relatively high activities were found in the
      fetal brain and declined at birth, while activities were insignificant in the
      fetal liver and rose following birth. There was a major peak in activity in
      pubertal female brains, but this peak was less important, and later, in males. No
      evidence was found to indicate that the low brain enzyme activities and high Km
      were attributable either to the presence of an inhibitor or to the steroid
      sulfation actually being a secondary activity of another brain sulfotransferase.
      We discuss whether the sulfotransferase activities found are adequate to
      synthesize the dehydroepiandrosterone and pregnenolone sulfate found in brain.

PMID- 9178431
TI  - Preparation of 3-ketodesogestrel metabolites by microbial transformation and
      chemical synthesis.
AB  - Specific microbial reactions were used for the preparation of metabolites of 3
      ketodesogestrel (13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-17 alpha-pregn
      4-en-20-yn-3-one, the active from of the progestagen desogestrel. Clostridium
      paraputrificum transformed 3-ketodesogestrel (KDG) to the 5 beta-dihydro and
      tetrahydro metabolites 13-ethyl-17 beta-hydroxy-11-methylene-18,19-dinor-5 beta,
      17 alpha-pregnan-20-yn-3-one and 13-ethyl-11-methylene-18,19-dinor-5 beta, 17
      alpha-pregnan-20-yne-3 alpha, 17 beta-diol, respectively. The epimeric compound
      13-ethyl-11-methylene-18,19-dinor-5 beta, 17 alpha-pregnan-20-yne-3 beta, 17 beta
      diol was obtained by chemical reduction of the 3-oxo compound. Mycobacterium
      smegmatis converted KDG to metabolites of the 5 alpha H-series: 13-ethyl-17 beta
      hydroxy-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yn-3-one, 13-ethyl
      11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 alpha, 17 beta-diol
      and 13-ethyl-11-methylene-18,19-dinor-5 alpha, 17 alpha-pregnan-20-yne-3 beta, 17
      beta-diol. The ring A-aromatized analog of KDG 13-ethyl-11-methylene-18,19-dinor
      17 alpha-pregna-1,3,5(10)-trien-20-yne-3,17 beta-diol was obtained by microbial 1
      dehydrogenation with Rhodococcus rhodochrous. Additionally, chemical syntheses of
      the microbially obtained KDG metabolites listed above were carried out. These
      included Birch reduction, reduction of KDG with sodium borohydride in aqueous
      pyridine and in methanol, reduction of KDG with potassium selectride in
      tetrahydrofuran, and dehydrogenation of KDG with cupric-II bromide in
      acetonitrile. The problems encountered in chemical syntheses favor the microbial
      procedures. The compounds were characterized by mass spectra (MS), IR, and
      circular dichroism (CD). Complete assignments of 1H and 13C chemical shifts were
      made using homo- and heteronuclear 2-DN-NMR spectroscopy. Chromatographic [gas
      liquid chromatography (GLC), high-performance liquid chromatography (HPLC), thin
      layer chromatography (TLC)] data of all the prepared KDG metabolites are
      presented.

PMID- 9178432
TI  - The sheep kidney contains a novel unidirectional, high affinity NADP(+)-dependent
      11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-3).
AB  - The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) enzymes convert
      corticosterone and cortisol to 11-dehydrocorticosterone and cortisone, and are
      thought to convey extrinsic specificity to the mineralocorticoid receptor by
      limiting access of the relatively more abundant glucocorticoids to it. Two
      different 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD) have been described
      and cloned. The liver-type, NADP(+)-dependent 11 beta-HSD-1, has an affinity in
      the micromolar range and bidirectional activity. The NAD(+)-dependent 11 beta-HSD
      2 has a higher affinity, in the nanomolar range, and exhibits only oxidase
      activity. 11 beta-HSD-2, because of its affinity and co-localization with the
      mineralocorticoid receptor, is likely to serve as the "gatekeeper" for the
      mineralocorticoid receptor in the kidney. Although the rat kidney expresses both
      isoforms, only the high-affinity, NAD(+)-dependent 11 beta-HSD-2 has been
      reported in the sheep kidney. We found both 11 beta-HSD NAD(+)- and NADP(+)
      dependent activities in sheep kidney to be present. The NAD(+)-dependent activity
      exhibited a Km similar to that reported in the literature, 3.85 +/- 1.28 nM for
      corticosterone and 21.3 +/- 5.8 for cortisol, was distributed in approximately
      equal amounts between microsomes and nuclei, and was unidirectional, converting
      corticosterone to 11-dehydrocorticosterone. The enzyme exhibited prominent
      substrate inhibition. The NADP(+)-dependent activity had a Km for corticosterone
      of 4 +/- 1.3 nM for a Km for cortisol of 35.2 +/- 2 nM, 100-fold lower than that
      described for the 11 beta-HSD-1 in the liver of sheep and other species, and was
      more prevalent in the microsomes than the nuclei. This enzyme was not inhibited
      by its substrate. The NAD(+)-dependent activity was approximately 3-10 times
      greater than the NADP(+)-dependent activity when incubated with 5 nM
      corticosterone substrate, but had similar activity when incubated with 100 nM
      substrate concentrations. CHOP cells (a modified Chinese hamster ovary cell line)
      transiently transfected with the sheep 11 beta-HSD-2 plasmid exhibited a marked
      preference for NAD+ as co-factor. Oxidation of corticosterone by transfected
      cells in the presence of NADP+ was present, but minimal; NADP+ did not support
      the metabolism of cortisol, the primary glucocorticoid of sheep. These data
      suggest the existence of another NADP(+)-dependent enzyme, 11 beta-HSD-3, which,
      because of its high affinity and unidirectional oxidase activity, may play a
      physiological role in the modulation of glucocorticoid binding to both the
      mineralocorticoid and glucocorticoid receptors.

PMID- 9178434
TI  - "Mammalian 3 alpha-hydroxysteroid dehydrogenases".

PMID- 9178433
TI  - Rapid hydrogenation of unsaturated sterols and bile alcohols using microwaves.
AB  - This paper describes an operationally simple, rapid hydrogenation of unsaturated
      sterols and bile alcohols in a domestic microwave oven. This has been achieved by
      the addition of catalytic amounts of Pd/C in methylene chloride/propylene glycol
      solvents in the presence of ammonium formate followed by microwave irradiation.
      It is suggested that this methodology will be helpful in the identification of
      saturated and unsaturated sterols with different side-chain structures in rare
      diseases: sitosterolemia, cerebrotendinous xanthomatosis (CTX), as well as
      atherosclerosis and diabetes mellitus. Sterols, such as cholesterol, campesterol,
      sitosterol, and bile alcohols with unsaturated side chains, were converted to
      their reduced congeners with high yield and purity.

PMID- 9178435
TI  - Drug treatment: explaining the gender paradox.
AB  - There is something of a gender paradox in drug user treatment. Research
      consistently indicates that women possess "risk factors" associated with drug use
      relapse, yet women are no more likely, and possibly less likely, to relapse to
      drug use. Efforts to explain this paradox involve a longitudinal study of 330
      women and men participating in outpatient drug-user treatment associated with the
      evaluation of the Los Angeles Target Cities Project funded by the Center for
      Substance Abuse Treatment. The findings offer no support for the drug severity
      and social support hypotheses, but some support for the treatment engagement
      hypothesis. Specifically, women participate more frequently in group counseling
      which, in turn, lowers their rate of relapse in spite of having more "risk
      factors." Further analyses indicate that the greater participation of women in
      group counseling does not stem from child-custody or other gender differences in
      the reasons for entering treatment, nor does it result from the enhanced services
      associated with the Target Cities Project. Rather, the differences in treatment
      engagement for women and men may result from gender norms concerning help
      seeking, personal independence, strength, and control. The treatment and policy
      implications of these findings and recommendations for further research are
      discussed.

PMID- 9178436
TI  - A "parliamentary inquiry" into alcohol and drugs: a survey of psychoactive
      substance use and gambling among members of the Dutch parliament.
AB  - In the fall of 1994 a survey was conducted on the use of alcohol and drugs and on
      gambling among members of the Dutch parliament. The survey indicated that almost
      two-thirds of the representatives sampled supported legalization of marijuana. A
      smaller majority (57%) was in favor of reducing the number of coffee shops
      selling marijuana. At least a quarter of the members of parliament had used
      marijuana themselves at one time or other. Alcohol consumption could be said to
      be "excessive" or "very excessive" for nearly 10% of the members of parliament.
      In general, the nature and extent of the parliamentarians' substance use was
      comparable to that in the Dutch general population.

PMID- 9178437
TI  - Reducing parental risk factors for children's substance misuse: preliminary
      outcomes with opiate-addicted parents.
AB  - Parents in methadone treatment were offered an experimental intervention, Focus
      on Families, designed to reduce their risk of relapse and their children's risk
      of substance use. Experimentally assigned volunteers participated in systematic
      group training in relapse prevention and parenting skills, and received home
      based case management services. Immediate posttreatment outcome results reported
      here include analyses of covariance controlling for baseline measures. Analyses
      show experimental parents held more family meetings to discuss family fun,
      displayed stronger refusal/relapse coping skills, demonstrated stronger sense of
      self-efficacy in role-play situations, and had lower levels of opiate use than
      control subjects. No significant differences in family bonding, family conflict,
      or other measures of drug use were found. The utility of intervening with drug
      addicted parents in methadone treatment is discussed in light of these findings.

PMID- 9178438
TI  - Rohypnol misuse in the United States.
AB  - Rohypnol, a potent sedative-hypnotic drug prescribed extensively throughout the
      world, is illicit in the United States. Recently, this drug has gained popularity
      among United States youths as a cheap means of intoxication and subsequently has
      become the focus of numerous criminal investigations. College men are alleged to
      slip Rohypnol tablets into unsuspecting women's drinks and then sexually abuse
      their sedated victims. Although law enforcement agencies and drug policy groups
      consider Rohypnol to be an "imminent problem," little is actually known about
      patterns of misuse. Presented here is a brief overview of Rohypnol's contemporary
      appearance in the United States.

PMID- 9178439
TI  - Drug dependence scale in the Millon Clinical Multiaxial inventory.
AB  - The Million Clinical Multiaxial Inventory (MCMI versions I, II, and III) includes
      a scale to assess drug use problems, Scale T-Drug Dependence. Detailed drug use
      data from a sample of 659 known drug users along with MCMI-II results were
      examined to determine the operating characteristics of the MCMI-II drug
      dependence scale. Operating characteristics, sensitivity, specificity, positive
      predictive power, negative predictive power, and overall diagnostic power were
      calculated for base rate cutoffs and for the number of prototypic items endorsed
      to determine the diagnostic efficiency of Scale T-Drug Dependence in identifying
      regular drug users. Prototypic item cutoffs provided higher levels of diagnostic
      and positive predictive power than did the standard base rate cutoffs.

PMID- 9178440
TI  - Drugs, crime, and HIV.
AB  - The use of criminal justice authority is discussed as a possibility for keeping
      drug users in treatment to decrease drug use, decrease injection, and to reduce
      the spread of HIV. It is hypothesized that the perception of treatment and
      control is a central factor in the limited use of criminal justice authority by
      community drug treatment providers.

PMID- 9178441
TI  - The rules of drug taking: wine and poppy derivatives in the ancient world. VI.
      Poppies as a source of food and drug.
AB  - Poppies were widely used during antiquity as a source of food, therapeutics, and
      poisons. It is likely that the alimentary value of poppy seeds was known in the
      Neolithic age, and there is some evidence that the neuropsychopharmacological
      effects of poppy juice were exploited during the Minoan civilization in the
      eastern Mediterranean basin. The Minoan civilization dates the attribution to
      poppies of symbolic meanings connected with rites of agricultural fertility. The
      persistence throughout antiquity of this symbolism is testified by literary and
      iconographic evidence of the attribution of poppies to goddesses of fertility,
      such as Demeter, Aphrodite, and Ceres.

PMID- 9178442
TI  - A prison-based alcohol use education program: evaluation of a pilot study.
AB  - Northern Territory prisoners were followed up after release to determine the
      effect of an alcohol education course on their alcohol consumption, drinking
      group, disruptive behavior, criminal activity, family relationships, how they use
      their time, general health, ability to cope and take responsibility. Measures
      were obtained both from prisoners and key informants, and two groups of prisoners
      were compared: those who completed the course and others who had not done the
      course. A high level of correspondence was found between measures from key
      informants and prisoners. The prisoners attending the course showed significant
      improvements on all dimensions when compared to the control subjects.

PMID- 9178443
TI  - Abstinence fear in methadone maintenance withdrawal: a possible obstacle for
      getting off methadone.
AB  - The present study attempts to shed light on methadone maintenance patients
      expectations regarding withdrawal symptoms during voluntary methadone
      detoxification. The study includes two groups of subjects; one group who have
      tried on their own initiative to terminate their methadone maintenance treatment
      (Group 1) and one group that contains rehabilitated patients who have not tried
      to quit using methadone (Group 2). Two main results have emerged. Group 1 has
      negative expectations beforehand about the intensity of withdrawal which
      significantly exceed the later, actual experience. Group 2 has negative
      expectations about the intensity of withdrawal that significantly exceed the
      negative expectations of Group 1. The clinical implications of these results are
      discussed.

PMID- 9178444
TI  - Clinical evaluation of ceramic veneered titanium restorations according to the
      Procera technique.
AB  - The aim of the present study was to present the design and one-year results of a
      study of crowns and fixed partial dentures (FPDs) made with the Procera system.
      All patients at one clinic needing fixed prosthodontic restorations during a two
      year period were invited. All 260 patients accepted to participate and they
      received 333 ceramic veneered Procera restorations-242 single crowns and 91 FPDs.
      The loss of patients during the one-year follow-up was only 5%. The restorations
      were evaluated according to a modified version of the California Dental
      Association rating system. Practically all Procera restorations were judged as
      satisfactory both at base line and at the one-year follow-up examination. Two
      crowns and one FPD showed fractures of the ceramic veneering. Another FPD had a
      fracture of a welded joint. Three single crowns came loose but could be
      recemented. In conclusion, the ceramic veneered Procera titanium restorations
      were well accepted by the patients and the success rate was high during the one
      year follow-up period.

PMID- 9178445
TI  - Remineralization of natural carious lesions with a glass ionomer cement.
AB  - Remineralization of carious lesions at the histological level is of great benefit
      since this will arrest lesion progression. The ability of glass ionomer cement
      (GIC) to (1) release fluoride it originally contains and (2) release "loosely
      bound" fluoride acquired from its surroundings have been previously demonstrated.
      This in vitro study examined the potential for caries remineralization if the
      lesion was placed near a GIC. Sixteen mesiodistal sections were cut through
      extracted deciduous molars exhibiting approximal white spot lesions. Sections
      were "linked" to a plastic tooth restored with a GIC to simulate the abutting
      surfaces of adjacent teeth. Lesions were photographed in water under polarized
      light initially and after one- and two-week exposures to artificial saliva. The
      photographs were digitized, lesion body outlined, and the area corresponding to
      the body of the lesion was determined to provide a comparison over time. Sixty
      two percent of the sections showed a quantitative reduction in lesion body size
      by an average of 43% after the first week and an additional 14% reduction after
      the second week. All but two sections demonstrated a qualitative change thereby
      illustrating that a reduction in pore volume size of the lesion body had also
      occurred. Therefore, fluoride released from a GIC has the potential to enhance
      remineralization of the early carious lesion in vitro. The greatest
      remineralization occurred during the first week of artificial saliva exposure.

PMID- 9178446
TI  - Preauricular approach to the temporomandibular joint: a postoperative follow-up
      on nerve function, hemorrhage and esthetics.
AB  - The aim of the present study was to report the incidence of facial and
      auriculotemporal nerve weakness, postoperative hemorrhage and disfiguring scars
      following TMJ surgery by the preauricular approach. One-hundred and fifty
      consecutive patients with a mean age of 37 years were studied. A total of 189
      surgical procedures were performed by the same surgeon. Facial nerve function was
      estimated the day after surgery and after six weeks. After 16 months facial and
      auriculotemporal nerve function was assessed and the patient's estimation of the
      scar was registered. Postoperative hemorrhage occurred after 1% of the
      operations. Five percent of the patients had transient facial nerve weakness.
      Auriculotemporal nerve weakness was reported by 34% of the patients. None of the
      patients found the scars disfiguring. Although neurosensory disturbances were
      frequently found in the temporal region, the preauricular incision offers a safe
      and cosmetically acceptable access to the temporomandibular joint.

PMID- 9178447
TI  - Children's dental health in Europe.
AB  - "Children's Dental Health in Europe" is a collaborative study of a total of 3200
      children, comprising samples of 5- and 12-year-old children from eight EU
      countries [Belgium, Germany, Greece, Ireland, Italy, Scotland (United Kingdom),
      Spain and Sweden] who have undergone clinical examination by well calibrated
      dentists. This study analyses the influence of a number of sociodemographic
      factors on the dental health of the actual children. Father's and/or mother's
      occupational status was used to determine the social class of the family, after
      construction of a family-social class variable, SocFam, and the accuracy of this
      variable was tested. In 15 of the 16 samples, both treatment provided and unmet
      treatment need were higher in children from low social class. The treatment need
      in children from low social class was significantly greater in the Belgium,
      German, Greek and Italian 5-year-old samples. The differences in both treatment
      need and treatment already received for children from high respectively low
      social class were significant in the Scottish and Spanish 12-year-old samples.
      Taking into account the total material of 1600 children in each age-group, risk
      indicators for caries, identified by logistic and multiple regression analyses,
      were social class of the family, the mother's smoking habits, and in the 5-year
      olds the number of siblings.

PMID- 9178448
TI  - Caries risk assessment in adolescents.
AB  - Detailed caries records and salivary microbiological tests were utilized to
      predict caries development in a group of 15-16-year-old Swedish adolescents.
      Both, caries experience and salivary microorganisms, correlated significantly
      with a subsequent 3-year increment of DFS. The strongest associations were
      recorded between the prevalence of baseline incipient lesions and the development
      of manifest caries (r = 0.51). Incipient lesions accounted for 27% of the 31%
      variability in the DFS increment explained by joined caries and salivary data.
      All predictors analysed showed insufficient sensitivity for identifying true
      caries active individuals. However, the combined sensitivity and specificity for
      incipient lesions and comprehensive caries record (incipient + manifest lesions)
      attained values allowing to predict caries development in the majority of
      individuals. Using precavity lesions as a sole predictor, 79-81% of the
      individuals were correctly classified with regard to their future caries levels.
      The addition of manifest caries increased the accuracy of classification to 86
      89% depending on the stringency of screening and validation criteria.

PMID- 9178449
TI  - Tobacco preventive measures by dental care staff. An attempt to reduce the use of
      tobacco among adolescents.
AB  - The purpose of the present study was to investigate the tobacco habits of
      children and adolescents within the catchment area of a public dental clinic
      before and after information about tobacco was given by dental care staff. The
      study was carried out over a three-year period on all 12- to 19-year-olds who
      came to the clinic for check-ups, 919, 933 and 859 individuals during each
      respective year. In the first year epidemiological data regarding use of tobacco
      were registered. Starting with the second year of the study coordinated
      information was given about the detrimental health effects of tobacco use. This
      consisted of individual information during the check-up, waiting-room
      information, and tobacco information in connection with dental health education
      in school. Use of tobacco was observed from the age of 14. Use was similar among
      boys and girls and increased with age. The proportion of tobacco users was 10.3%,
      11.5%, and 7.3% for the respective years of the study. Statistical analysis shows
      that the reduction between the second and third year of the study is significant
      (p < 0.05). The result supports the hypothesis that tobacco information conveyed
      by dental care staff can influence the tobacco habits of children and
      adolescents.

PMID- 9178451
TI  - Developmental and dysmorphogenic effects of glufosinate ammonium on mouse embryos
      in culture.
AB  - The effects of glufosinate ammonium on embryonic development in mice were
      examined using whole embryo and micromass cultures of midbrain and limb bud
      cells. In day 8 embryos cultured for 48 hr, glufosinate caused significant
      overall embryonic growth retardation and increased embryolethality to 37.5% at 10
      micrograms/ml (5.0 x 10(-5) M). All embryos in the treated groups exhibited
      specific morphological defects including hypoplasia of the prosencephalon
      (forebrain) (100%) and visceral arches (100%). In day 10 embryos cultured for 24
      hr, glufosinate significantly reduced the crown-rump length and the number of
      somite pairs, and produced a high incidence of morphological defects (84.6%) at
      10 micrograms/ml. These embryos were characterized by blister in the lateral head
      (100%), hypoplasia of prosencephalon (57.1%), and cleft lips (42.9%) at 20
      micrograms/ml (10.0 x 10(-5) M). Histological examination of the treated embryos
      showed numerous cell death (pyknotic debris) present throughout the
      neuroepithelium in the brain vesicle and neural tube, but did not involve the
      underlying mesenchyme. In micromass culture, glufosinate inhibited the
      differentiation of midbrain cells in day 12 embryos with 50% inhibition occurring
      at 0.55 microgram/ml (2.8 x 10(-6) M). The ratios of 50% inhibition concentration
      for cell proliferation to cell differentiation in limb bud cells were 0.76 and
      1.52 in day 11 and 12 embryos, respectively. These findings indicate that
      glufosinate ammonium is embryotoxic in vitro. In addition to causing growth
      retardation, glufosinate specifically affected the neuroepithelium of the brain
      vesicle and neural tube, leading to neuroepithelial cell death.

PMID- 9178450
TI  - Traumatic oral vs non-oral injuries.
AB  - This study comprised patients who sought consultation or treatment from a
      physician or dentist for injury caused by accident in a Swedish county
      (Vastmanland 256510 inhabitants) during a period of one year. A total of 23690
      (adjusted for non-responders) individuals were injured during the study period.
      Five per cent included oral injuries, 95% non-oral injuries, and 0.4% consisted
      of both oral and non-oral injuries. In total, oral injuries were the sixth most
      common part of the body that was injured. The incidence of oral injuries was
      4.2/1000 inhabitants/year and of non-oral injuries 87.8/1000/year. Because
      practically all oral injuries were observed in individuals under the age of 30,
      the comparison between oral and non-oral injuries was made for the age interval 0
      30 years. The highest risk of sustaining oral injuries was in the ages 0-12
      years, where the annual incidence was 18/1000, making oral injuries the third
      most common form of injury. The study reveals substantial differences between
      oral and non-oral injuries with regard to age-groups, site of injury, and injury
      mechanism. Falls were the most common cause of oral injuries among those 0-6
      years of age, whereas push and hit were the primary causes of oral injuries in
      the ages 16-30 years. Non-oral injuries were caused most frequently by falls in
      all age groups. Alcohol and violence were more likely related to oral than non
      oral injuries for persons in the age interval 16-30 years. The number of oral
      injuries was higher during weekends and in the late evenings than at other times,
      whereas most non-oral injuries occurred during day-time hours, and were spread
      evenly throughout the week. The high incidence and special characteristics of
      oral injuries stress the importance of including oral injuries to achieve a high
      validity in body injury surveillance systems. Furthermore, the results indicate
      that epidemiological data are unique for oral injuries which should be taken into
      consideration when planning for prevention and organization of emergency
      resources.

PMID- 9178452
TI  - Male-mediated teratogenesis: spectrum of congenital malformations in the
      offspring of A/J male mice treated with ethylnitrosourea.
AB  - Male mice of inbred strain A/J were intraperitoneally treated with
      ethylnitrosourea (ENU). On day 64-82 posttreatment, the males were mated with
      untreated virgin females of the same strain. Copulation involved sperm that were
      spermatogonial stem cells at the time of treatment. On day 18 of gestation,
      viable fetuses were inspected for external malformations. The most common
      malformation to occur spontaneously in the control group was cleft palate or
      cleft lip. Similarly, in the ENU-treated series, cleft palate or cleft lip was
      the predominant malformation, the frequency (15%) of which was significantly
      increased in the highest dose group (5 x 50 mg/kg) compared to control (8%).
      Based on these results and other data, we propose that a large fraction of
      external malformations in fetuses from mutagenized paternal germ cells are a
      result of increased yields of spontaneously occurring malformations.

PMID- 9178453
TI  - Evaluation of the developmental toxicity of 4-bromobenzene using frog embryo
      teratogenesis assay--Xenopus: possible mechanisms of action.
AB  - Potential mechanisms of 4-bromobenzene-induced developmental toxicity were
      evaluated using frog embryo teratogenesis assay-Xenopus (FETAX). Early X, laevis
      embryos were exposed to 4-bromobenzene in two separate definitive concentration
      response tests with and without an exogenous metabolic activation system (MAS) or
      selectively inhibited MAS. The MAS was treated with carbon monoxide (CO) to
      modulate P-450 activity, cyclohexene oxide (CHO) to modulate epoxide hydrolase
      activity, and diethyl maleate (DM) to modulate glutathione conjugation. Addition
      of the intact MAS, and particularly the CHO- and DM-inhibited MASs, dramatically
      increased the embryo lethal potential of 4-bromobenzene. Addition of the CO
      inhibited MAS decreased the developmental toxicity of activated 4-bromobenzene to
      levels approximating that of the parent compound. Results from these studies
      suggested that a highly toxic arene oxide intermediate of 4-bromobenzene formed
      as the result of mixed function oxidase (MFO)-mediated metabolism may play an
      important role in the development toxicity of 4-bromobenzene in vitro.
      Furthermore, both epoxide hydrolase and glutathione conjugation appeared to be
      responsible for activated 4-bromobenzene detoxification.

PMID- 9178454
TI  - Inhibitory effects of phenolic compounds on development of naturally occurring
      preneoplastic hepatocytic foci in long-term feeding studies using male F344 rats.
AB  - Five phenolic compounds, namely caffeic acid, sesamol, hydroquinone, catechol,
      and 4-methoxyphenol, were fed to groups of 30 male F344 rats at dietary levels of
      2, 2, 0.3, 0.8, and 2%, respectively, for 2 years. Retardation of body weight and
      elevated relative liver weights were noted for all groups. Formalin-fixed and
      paraffin-embedded liver tissues from rats killed terminally were cut and stained
      for glutathione S-transferase placental form (GST-P) and tumor growth factor
      alpha (TGF alpha) immunohistochemically. Numbers and areas of GST-P-positive (GST
      P+) foci per unit area of liver section were measured, and the respective
      treated/control proportional values were calculated to be 58 and 57% for caffeic
      acid. 58 and 54% for sesamol, 71 and 71% for hydroquinone. 58 and 133% for
      catechol, and 49 and 39% for 4-methoxyphenol. These data were comparable with
      results obtained with medium-term liver bioassays (Ito test). However, no
      intergroup differences were detected with regard to quantitative findings for TGF
      alpha foci, which were relatively rare. Long-term inhibitory effects of phenolic
      compounds on liver carcinogenesis, predicted from the Ito test, were thus
      confirmed in the present feeding studies using quantitative analysis of
      immunohistochemically demonstrable GST-P+ foci as end point marker lesions.

PMID- 9178455
TI  - Induction of feline immunodeficiency virus specific antibodies in cats with an
      attenuated Salmonella strain expressing the Gag protein.
AB  - Salmonella typhimurium aroA strains (SL3261), expressing high levels of the Gag
      protein of feline immunodeficiency virus (FIV) fused with maltose binding protein
      (SL3261-MFG), were constructed using an invertible promoter system that allows
      the stable expression of heterologous antigens at levels toxic for bacteria. A
      SL3261 strain expressing the B subunit of cholera toxin by a similar system
      (SL3261-CtxB) served as a control in FIV-immunization experiments. Cats immunized
      once orally or intraperitoneally with SL3261-MFG or SL3261-CtxB all developed
      serum antibodies to SL3261 lipopolysaccharide and against maltose binding protein
      or the B subunit of cholera toxin, respectively. Two intraperitoneal
      immunizations with SL3261-MFG also resulted in the development of Gag specific
      serum antibodies. Two oral immunizations with SL3261-MFG primed for a Gag
      specific response, which was demonstrated upon FIV challenge. All challenged cats
      became infected and no significant differences in viral loads were found between
      SL3261-MFG and SL3261-CtxB immunized cats.

PMID- 9178456
TI  - Determinants and kinetics of cytokine expression patterns in lungs of vaccinated
      mice challenged with respiratory syncytial virus.
AB  - The development of a successful respiratory syncytial virus (RSV) vaccine will be
      advanced by an improved understanding of the pathogenesis of natural disease and
      vaccine-enhanced illness. Using a murine model, we have examined cytokine message
      expression and cytokine secretion in lungs of mice primed with killed or live
      antigens and challenged with RSV. Stable cytokine mRNA expression was achieved if
      the prime-challenge interval was 2 weeks. The pattern of expression of
      interleukin-4 (IL-4) and interferon-7 (IFN-gamma 1 mRNA was established by day 4
      after challenge and was maintained at least through day 12, and was not affected
      by the concentration of priming immunogen or virus challenge. An enzyme-linked
      immunospot assay demonstrated that CD4+ T cells were responsible for the
      production of IL-4, while many cell types secreted IFN-gamma. These experiments
      begin to define the kinetics of cytokine expression and phenotypes of cytokine
      producing cells following RSV infection, supporting previous findings that
      suggested aberrant infiltration of CD4+ T lymphocytes and excessive IL-4
      secretion may play a role in the vaccine-enhanced disease associated with RSV.

PMID- 9178457
TI  - Immunogenic and protective properties of haemagglutinin protein (H) of rinderpest
      virus expressed by a recombinant baculovirus.
AB  - The hemagglutinin (H) protein of Rinderpest virus expressed by a recombinant
      baculovirus used as a vaccine produced high titres of neutralizing antibody to
      Rinderpest virus in the vaccinated cattle, comparable to the levels produced by
      live attenuated vaccine. The immunized cattle were protected against a vaccine
      virus challenge, as demonstrated by the failure of development of antibodies to N
      protein of the vaccine virus. The lack of replication of vaccine virus in the
      immunized cattle indicated that they are capable of showing a protective response
      if challenged with a virulent virus.

PMID- 9178458
TI  - Potency testing of tissue culture rinderpest vaccine in rabbits.
AB  - Rinderpest (RP) vaccine potency testing requires virulent bovine rinderpest virus
      (RPV). Use of virulent RPV is a biosafety hazard. In this study we had vaccinated
      rabbits with tissue culture RP vaccine at different doses and thereafter
      challenged with lapinized virus. No thermal reaction in vaccinated rabbits was
      observed. Serum neutralizing antibody response to vaccine was dose dependent
      until the second week post-vaccination but by the fourth week post-vaccination
      all the rabbits had similar neutralizing antibody titres. Vaccinated rabbits
      exhibited mild clinical signs as compared to unvaccinated controls after
      challenge. All the vaccinated rabbits survived challenge while only 40%
      unvaccinated rabbits survived challenge with virulent lapinized RPV. A strong
      anamnestic response in all the vaccinated rabbits was observed after challenge
      with lapinized virus. This study shows that rabbits could be used for potency
      testing of RP vaccine virus.

PMID- 9178459
TI  - Inactivated hepatitis A vaccine: long-term antibody persistence.
AB  - During the clinical development of safe, well tolerated and immunogenic vaccines
      against hepatitis A the persistence of protective antibodies was estimated, based
      on relatively short observation periods of 18 months to 3 years. We report here
      on longterm persistence of antibodies in volunteers who participated in one of
      the early clinical trials on inactivated hepatitis A candidate vaccines. In a
      randomized trial three groups of altogether 110 healthy adults, initially
      hepatitis A virus (HAV) seronegative persons were vaccinated with an inactivated
      hepatitis A vaccine according to the schedule 0-1-2-12 months. One group received
      180 ELISA units, one group 360, and one 720 ELISA units per dose. Blood samples
      were taken prior to the first vaccination and at months 1, 2, 3, 4, 6, 12, 13,
      18, 24, 36 and 84. The decrease of antibodies was characterized by two
      disappearance rates: a rapidly decreasing component and a slower decreasing one
      becoming predominant ca 12 months after booster vaccination. The disappearance of
      antibodies could be described by a two-component model which holds for t > or =
      13 months. The estimated disappearance rates for the slow component (annual
      decrease) was found to be 11 and 13% for the 180 and 360 El. U groups,
      respectively (the 720 El. U group showed no decline, which was probably due to
      the small sample size). The estimated persistence of antibodies within protective
      range varied between 24 and 47 years depending on individual titres reached at
      month 13 and vaccination dose.

PMID- 9178460
TI  - Protection against tetanus toxin in mice nasally immunized with recombinant
      Lactococcus lactis expressing tetanus toxin fragment C.
AB  - Mice inoculated intranasally (i.n.) with a recombinant strain of live Lactococcus
      lactis expressing tetanus toxin fragment C (TTFC), produced both serum and
      secretory antibodies to TTFC. Killed bacteria which had accumulated TTFC
      intracellularly in vitro also elicited protective serum antibody responses. There
      was no requirement for either colonization or invasion of the mucosa. In addition
      secretory antibody responses in the lung and nasal tissues were elicited after
      i.n. inoculation in the presence of an adjuvant.

PMID- 9178461
TI  - Passive immunity against measles during the first 8 months of life of infants
      born to vaccinated mothers or to mothers who sustained measles.
AB  - Neutralizing antibody titers of 47 infants whose mothers sustained measles
      (measles group) and 70 whose mothers were vaccinated (vaccine group) were
      compared at birth, 4 and 8 months of age. All children had antibodies at birth
      and 88% at 4 months. At 8 months, 49% had antibodies in the measles group and 15%
      in the vaccine group (P < 0.001). The geometric mean titers were significantly
      lower in the vaccine group than in the measles group and the difference
      corresponded to the antibody loss occurring in only 1.5 months of life. This
      small difference may reflect past exposure to wild virus of many vaccinated
      mothers.

PMID- 9178462
TI  - Total and isotype humoral responses in cattle vaccinated with foot and mouth
      disease virus (FMDV) immunogen produced either in bovine tongue tissue or in BHK
      21 cell suspension cultures.
AB  - The anti-foot and mouth disease virus (FMDV) serum antibody activity of protected
      and non protected animals immunized with inactivated FMDV originated in either
      bovine tongue tissue (BTTV vaccines) or BHK-21 cell suspension cultures (BHKV
      vaccines) was evaluated. The results show that 80-100% of the BTTV immunized and
      only 40-60% of the BHKV immunized animals with liquid-phase blocking sandwich
      ELISA (lp ELISA) serum titres of 1.5-1.7 U, were protected against the challenge
      with any of the four infectious FMDV argentine reference strains. This difference
      becomes almost marginal among BTTV and BHKV vaccinated animals with a strong anti
      FMDV humoral response (i.e. lp ELISA titres > or = 1.95 U). Isotyping of the anti
      FMDV response in immunized cattle with low lp ELISA titres revealed that BTTV
      vaccines were able to induce remarkably higher anti-FMDV IgG1 titres than their
      BHKV counterparts (i.e. mean titres of 1.95 and 1.35 U. respectively). This
      difference in specific IgG1 serum levels induced by BTTV and BHKV vaccines seems
      to be also limited to those animals with low anti-FMDV lp ELISA titres. These
      results together with the fact that the specific serum IgG1, but not the IgG2,
      isotype response of 219 vaccinated animals correlates almost linearly with their
      capacity to pass the challenge, suggests that the superior performance of BTTV
      vaccines is close related to their ability to raise a stronger anti-FMDV IgG1
      response than BHKV vaccines.

PMID- 9178463
TI  - Anthrax post-vaccinal cell-mediated immunity in humans: kinetics pattern.
AB  - Seven groups (2596 subjects) were vaccinated with a human live anthrax vaccine
      (HLAV) by three different routes (scarification, subcutaneous and aerosol). The
      vaccinees were tested for anthrax cell-mediated immunity using the "Anthraxin"
      skin test at 7, 15, 30, 90, 180 and 365 days following vaccination. The kinetic
      pattern obtained from all groups, shows a significant, five-phased curve: phase I
      (2-6 days post-vaccination) shows a slow increase in positive Anthraxin skin
      reactions. Phase II (7-15 days post-vaccination) shows an exponential rise to a
      maximum at day 15. Phase III (16-30 days post-vaccination) shows a decrease to
      day 30. Phase IV (31-90 days post-vaccination) leads to a relative restoration of
      the positive skin reactions. During phase V (91-365 days post-vaccination) there
      is a continuous decrease in positive Anthraxin skin reactions. The loss of the
      skin test reaction on day 30 is a characteristic feature of post vaccination
      anthrax cell-mediated immunity. It may be due to a blockade of macrophages by
      lethal anthrax toxin released by the multiplying vaccine strain. Epidemiological
      observations of HLAV protective rates correlate with the phases of the skin
      reaction kinetics.

PMID- 9178464
TI  - Comparison between hepatitis B surface antigen (HBsAg) particles derived from
      mammalian cells (CHO) and yeast cells (Hansenula polymorpha): composition,
      structure and immunogenicity.
AB  - The composition, structure and immunogenicity of hepatitis B surface antigen
      (HBsAg) particles derived from Chinese hamster ovary (CHO) cells and from cells
      of the yeast Hansenula polymorpha were compared. The particles were similar in
      size distribution (mean 20-33 nm), in shape (spherical), in gross composition
      (protein to lipid weight ratio of 60:40), and in types of lipids (phospholipids >
      > sterols = sterol esters = triacylglycerols). Differences related to genetic
      engineering and type of host cells were found in peptide and lipid compositions.
      CHO-HBsAg has three peptides: S, M and L, each in two forms of glycosylation,
      while the Hansenula-HBsAg has only the nonglycosylated S peptide. The electrical
      surface potential at the lipid/water interface of HBsAg derived from Hansenula is
      more negative than that of HBsAg derived from CHO, which was close to neutrality.
      Although the numbers of cysteine residues (all in the S peptides) are identical
      (14), 11 of them are free thiols in the CHO-HBsAg, compared with three to four in
      the Hansenula-HBsAg. The fact that 85% of the phospholipids are hydrolyzed by
      phospholipase C and that all the aminophospholipids react with
      trinitrobenzenesulfate suggests that the particles derived from both cell types
      are either leaky vesicles or have a lipoprotein-like structure. Subcutaneous
      injection into mice of fluorescein-isothiocyanate-labeled HBsAg particles from
      both sources resulted in their accumulation in the marginal sinus of lymph nodes.
      The humoral responses to subcutaneous injection into mice of CHO- and Hansenula
      HBsAg were similar: however, the cytotoxic T lymphocyte response to CHO-HBsAg was
      lower.

PMID- 9178465
TI  - Recognition of contiguous allele-specific peptide elements in the rubella virus
      E1 envelope protein.
AB  - Peptides which bind to human HLA-DRB1 class II molecules in an allele-specific
      fashion were derived from the immunodominant E1 envelope protein of rubella
      virus. Two nonoverlapping E1 peptide epitopes were recognized by rubella virus
      specific T cells in the context of independent HLA alleles when presented either
      separately or as a contiguous polypeptide containing both epitopes. Direct
      binding analysis of potential peptide epitopes to distinct HLA molecules provides
      a direct approach for selecting antigenic peptides useful for epitope-based
      vaccine targeted to multiple HLA types.

PMID- 9178466
TI  - Protective responses in mice to vaccination with multiply administered cold
      adapted influenza vaccine reassortants and wild-type viruses.
AB  - Protective responses to influenza vaccine reassortants derived from the cold
      adapted (ca) donor strains A/Leningrad/134/17/57 and B/USSR/60/69 and wild-type
      epidemic viruses were studied in two strains of mice. Preliminary experiments
      revealed that, when mixtures of three viruses were inoculated intranasally to
      mice with 50 microliters containing 10(6) EID50 per 200 microliters (10(5.4)
      EID50 per mouse), interference between strains did not occur. However,
      interference with the growth of the influenza reassortant B/60/32/R took place if
      its concentration in the mixture was reduced to 10(5) (10(4.4) per mouse) or if
      it was inoculated at 10(6) EID50 (10(5.4) per mouse) in the presence of the
      influenza reassortant R/34 and two other influenza A epidemic strains;
      interference was unrelated to serological responses to infection with B/60/32/R.
      Despite evidence of interference, mice inoculated with the same mixtures in two
      identical doses, three weeks apart, were able to clear a challenge from each of
      seven homotypic and heterotypic influenza A and B strains. Heterotypic clearance
      of influenza A challenge viruses was greater following mixed infection,
      indicating that common determinants within the surface antigen glycoproteins
      contributed to immune responses which were broader than could be expected to be
      induced by parenteral vaccination.

PMID- 9178467
TI  - Protection in a gerbil model of amebiasis by oral immunization with Salmonella
      expressing the galactose/N-acetyl D-galactosamine inhibitable lectin of Entamoeba
      histolytica.
AB  - Infection with the enteric parasite Entamoeba histolytica can result in colitis
      and dysentery as well as abscesses at extra-intestinal sites. An effective
      vaccine must be able to protect against both mucosal and systemic disease. In
      this study an attenuated Salmonella strain that expressed a portion of the GalNAc
      lectin of E, histolytica was used to orally immunize gerbils. Animals were
      challenged by intrahepatic injection of amebic trophozoites. A significant
      decrease in size of amebic liver abscesses was observed in orally immunized
      animals. Oral immunization with a Salmonella-based vaccine was as effective as
      systemic immunization for protection against systemic challenge.

PMID- 9178468
TI  - Intracutaneous vaccination of rabbits with the cottontail rabbit papillomavirus
      (CRPV) L1 gene protects against virus challenge .
AB  - A DNA vaccine encoding the major capsid protein L1 of cottontail rabbit
      papillomavirus (CRPV) was constructed and administered intracutaneously (i.c.) to
      rabbits as supercoiled plasmids bound to gold beads using a specialized delivery
      device ("gene gun"). L1 DNA-vaccinated rabbits developed cellular proliferative
      responses to CRPV virus-like particles and developed high titered antibodies with
      neutralizing activity to CRPV. Following experimental challenge with CRPV, all of
      the L1 DNA-vaccinated rabbits, vs none of the controls, were protected from
      papilloma formation. These results demonstrate that i.c. vaccination of rabbits
      with the L1 papillomavirus capsid gene can induce antibodies that protect against
      subsequent papillomavirus infection.

PMID- 9178469
TI  - Determination of protein loading in biodegradable polymer microspheres containing
      tetanus toxoid.
AB  - Various methods to determine loading of vaccine in biodegradable polymer
      microspheres encapsulating tetanus toxoid were evaluated. The microspheres were
      composed of poly (D-lactic acid) (PLA) and poly (DL-lactic-co-glycolic acid)
      (PLGA). Dissolution of microspheres in organic solvents such as methylene
      chloride, chloroform, or dimethyl sulfoxide and extraction of vaccine antigen or
      total protein with phosphate buffered saline gave variable results which depended
      upon the characteristics of the microspheres, such as type of polymer, excipients
      used in the microspheres and formulation conditions. Microspheres made from low
      molecular weight PLGA polymer and showing a large burst release exhibited up to
      25% extraction of antigen whereas microspheres made from PLA microspheres with
      low burst release showed < 1% extraction. Extraction of total protein with 0.1 N
      NaOH and 5% sodium dodecyl sulfate showed results similar to those obtained with
      organic solvent extraction method. Partial digestion of microspheres with 6 N HCl
      at 60 degrees C for 20 h resulted in approximately 30% loss in TT protein by
      micro-bicinchoninic acid (BCA) assay. The major problem with this method was
      strong reactions in the micro-BCA assay of stabilizers, particularly sugars
      (glucose, sucrose) used in the microsphere formulations. Complete digestion of
      microspheres with 6 N HCl at 110 degrees C for 20 h or with 13.5 N NaOH at 121
      degrees C for 1 h and quantitation of amino acids by a modified ninhydrin assay
      showed reproducible results on the protein loading in the microspheres. However,
      this method was affected by the presence of stabilizers, such as gelatin, which
      contain amino acids. Further, sucrose concentrations higher than 10% caused
      interference in the ninhydrin assay on samples hydrolyzed with 6 N HCl. In
      contrast, hydrolysis with 13.5 N NaOH did not show any interference by sucrose.
      Stabilizers used outside the microspheres for lyophilization purposes may be
      removed by washing the microspheres before loading determination or by dialysis
      but stabilizers used inside the microspheres would still cause interference. For
      reliable determination of total protein in the microspheres containing vaccines,
      we suggest complete digestion of microspheres with acid or base followed by amino
      acid analysis by colorimeteric assays such as ninhydrin method or using amino
      acid analyzers. The method needs to be optimized for each type of formulation to
      eliminate interference by the excipients. Alternatively, total protein nitrogen
      in the microspheres may be determined by the Kjel-dahl method if no amino acids
      or other nitrogen containing stabilizer is used inside the microspheres.

PMID- 9178470
TI  - Yeast-secreted bovine herpesvirus type 1 glycoprotein D has authentic
      conformational structure and immunogenicity.
AB  - Bovine herpesvirus-1 (BHV-1) glycoprotein D (gD), an envelope glycoprotein,
      engenders mucosal and systemic immunity protecting cattle from viral infection.
      Production of gD with authentic immunogenicity is required for a subunit vaccine.
      We placed the truncated BHV-1 gD gene, lacking its putative transmembrane and
      cytoplasmic domains, under the control of the methanol-inducible AOX1 promoter in
      the yeast Pichia pastoris. Truncated BHV-1 gD (tgD) was efficiently secreted into
      the culture medium as a 68 kDa protein using either the yeast alpha prepro or
      native BHV-1 gD signal sequences. The yeast-secreted tgD had N-linked
      glycosylation and appears to have authentic conformational structure and
      immunogenicity based on the following observations A panel of monoclonal
      antibodies recognizing five neutralizing epitopes reacted with yeast tgD. Sera
      from yeast tgD-immunized mice immunoprecipitated native BHV-1 gD and neutralized
      BHV-1 infection in vitro. Yeast tgD competitively blocked all reaction between
      native gD and monospecific gD polyclonal sera from cattle. Based on these data,
      yeast-derived BHV-1 tgD is an excellent candidate for a subunit vaccine.

PMID- 9178471
TI  - Immunobiological properties of a 30 kDa secretory protein of Mycobacterium
      tuberculosis H37Ra.
AB  - Six different secretory proteins of molecular weights (15, 26, 30, 41, 55 and 70
      kDa) were isolated from 8-day-old culture filtrate of Mycobacterium tuberculosis
      H37Ra using different column chromatography techniques. These proteins were
      further examined for their ability to induce cell mediated (T-cell proliferation
      assay) and humoral immune response (ELISA) in mice immunized with total culture
      filtrate proteins. Out of six proteins, three proteins showed good reactivity.
      However, the activity was at a maximum with 30 kDa antigen. The immune response
      induced by 30 kDa antigen emulsified in Freund's incomplete adjuvant (FIA) was
      investigated and was found to be dose dependent. The T-cell response induced by
      this protein was skewed towards T-helper (Th1) cells as determined by the
      pronounced secretion of interleukin-2 (IL-2) and gamma-interferon (IFN-gamma).
      The protective activity of the 30 kDa protein was also evaluated and compared
      with reference to Bacillus Calmette Guerin (BCG) vaccine in the mice challenged
      with virulent M. tuberculosis H37Rv. The degree of protection afforded by the 30
      kDa antigen on the basis of mortality and the significant decrease in c.f.u.'s
      recovered from different organs (lung, liver, spleen) after 30 days of challenge
      with LD50 of M. tuberculosis H37Rv was significantly higher in comparison to BCG
      vaccinated animals. However, the degree of immunity induced by this antigen
      decreased with time (when challenged 8 and 12 weeks post-immunization) but it was
      still comparable with BCG. These findings suggest that 30 kDa secretory protein
      of M. tuberculosis is the key immunoprotective antigen and may be a suitable
      candidate for the development of an alternative subunit vaccine against
      tuberculosis.

PMID- 9178472
TI  - A murine model of intranasal immunization to assess the immunogenicity of
      attenuated Salmonella typhi live vector vaccines in stimulating serum antibody
      responses to expressed foreign antigens.
AB  - The lack of a practical small animal model to study the immunogenicity of
      Salmonella typhi-based live vector vaccines expressing foreign antigens has
      seriously impeded the vaccine development process. For some foreign antigens,
      stimulation of serum IgG antibody is the desired, protective immune response. We
      administered to mice, by orogastric or intranasal (i.n.) routes, attenuated delta
      aroC delta aroD S. typhi CVD 908 carrying a plasmid encoding fragment C (fragC)
      of tetanus toxin fused to the eukaryotic cell receptor binding domain of
      diphtheria toxin (fragC-bDt), and monitored serum antibody. While orogastric
      inoculation of three doses was not immunogenic, i.n. immunization elicited high
      titers of serum IgG tetanus antitoxin, generating peak ELISA geometric mean
      titers (GMT) of 27024 and 35658 with 10(8) and 10(9) c.f.u. dosages,
      respectively; 10(9) c.f.u. i.n. of an delta aroA S. typhimurium live vector
      stimulated a peak antitoxin GMT of 376 405. Mice immunized with the S. typhi live
      vector were 100% protected against challenge with 100 50% lethal doses of tetanus
      toxin that rapidly killed all control mice. Intranasal immunization with two
      doses of S. typhi expressing unfused fragment C under control of an anaerobically
      activated promoter derived from nirB stimulated significantly higher titers of
      serum neutralizing antitoxin than fused fragC-bDt controlled by the same promoter
      (GMT 0.10 AU ml-1 vs 0.01 AU ml-1, P = 0.0095). Two i.n. doses of S typhi
      encoding fragC under control of powerful constitutive promoter 1pp led to
      significantly higher peak serum neutralizing antitoxin titers than the otherwise
      identical construct utilizing the nirB promoter (peak GMT 0.72 AU ml-1 vs 0.10 AU
      ml-1, P = 0.022). The i.n. route of inoculation of mice may constitute a
      practical breakthrough that could expedite the development of some S. typhi-based
      live vector vaccines by allowing, for the first time, quantitative measurement of
      serum antibody responses to candidate constructs following i.n. mucosal
      immunization.

PMID- 9178473
TI  - Induction of neutralizing antibody and T-cell responses to varicella-zoster virus
      (VZV) using Ty-virus-like particles carrying fragments of glycoprotein E (gE).
AB  - During infection with Varicella-zoster virus (VZV), the envelope proteins are
      highly immunogenic and glycoprotein E (gE) is one of the most abundant and
      antigenic. We have previously identified the immunodominant regions of gE and
      mapped the B-cell epitopes. In this study, we have evaluated the immunogenicity
      of recombinant hybrid Ty-virus-like particles (VLPs) carrying amino acids (1-134)
      or (101-161) of gE which contain the immunodominant sequences. VZV-specific
      antibodies were detected by ELISA in sera from mice and guinea pigs immunized
      with either gE(1-134)-VLPs or gE (101-161)-VLPs. The dominant B-cell epitopes,
      mapped by pepscan analysis of the sera, were found in peptides spanning amino
      acids 41-60, 56-75, 101-120, 116-135, 131-150 and 141-161. These sera also showed
      neutralizing activity against VZV in vitro. Epitopes recognized by neutralizing
      MAbs were mapped to both gE sequences (3B3 MAb recognizing amino acids 141-161
      and IFB9 MAb recognizing amino acids 71-90). Lymphocyte proliferative responses
      to VZV were detected in four different mouse strains immunized with either gE(1
      134)-VLPs or gE(101-134)-VLPs in alum. All mouse strains immunized with gE(1-134)
      VLPs recognized epitopes in amino acids 11-30 and 71-90 and all those immunized
      with gE(101-161)-VLPs recognized epitopes in amino acids 91-110 and 106-125.
      These results indicate that VLPs carrying these gE sequences can prime potent
      humoral and cellular anti-VZV responses in small animals and warrant further
      investigation as potential vaccine candidates against varicella-zoster
      infections.

PMID- 9178474
TI  - Canine parvovirus vaccine elicits protection from the inflammatory and clinical
      consequences of the disease.
AB  - Inflammatory changes following infection are central to the clinical
      manifestation of disease. However, information regarding such changes in animal
      disease is limited. In canine parvovirus infected puppies we measured the levels
      of acute phase proteins and changes in leukocyte phenotypes and cell trafficking
      by flow cytometry. These parameters correlated with conventional assessment of
      clinical disease in a vaccine efficacy study. Seropositive (CPV-2) 6-week-old
      puppies given three doses of a CPV-2 containing vaccine developed significant
      antibody titers and remained healthy after experimental infection with CPV-2b.
      Unvaccinated controls developed clinical signs and shed virus. Importantly, acute
      phase proteins became elevated, and lymphopenia, neutropenia and modulation of
      neutrophil-CD4 were detected in controls but not in vaccinates.

PMID- 9178475
TI  - The bovine parainfluenza virus type-3 (BPIV-3) hemagglutinin/neuraminidase
      glycoprotein expressed in baculovirus protects calves against experimental BPIV-3
      challenge.
AB  - Despite the availability of numerous vaccine schedules, "shipping fever", an
      acute bronchopneumonia brought on in part by a complex of bovine respiratory
      viruses, remains a major source of economic loss in the beef and dairy
      industries. We are exploring new strategies of bovine vaccine design which we
      hope may provide more effective and more cost-efficient control of these
      pathogens. In this report, we examined the possible use of subunit vaccines,
      using as an example the hemagglutinin/neuraminidase (HN) protein of bovine
      parainfluenza virus type-3 (BPIV-3) expressed in the baculovirus expression
      system. We showed that the protein was expressed at high levels, and was modified
      to a similar, but not identical size as the native HN protein expressed from BPIV
      3 infected bovine cells. We further demonstrated antigenicity and biological
      activity of the expressed HN protein. Finally, we vaccinated colostrum deprived
      sera-negative calves with the baculo HN recombinant protein and challenged with
      BPIV-3. Vaccination induced excellent serum neutralizing antibody responses, and
      surprisingly, good mucosal antibody responses, even though the vaccine was
      administered parenterally. The vaccinated animals were well protected against
      challenge.

PMID- 9178476
TI  - Oral delivery of purified lipoprotein OspA protects mice from systemic infection
      with Borrelia burgdorferi.
AB  - The lipoprotein outer surface protein A (OspA) of the Lyme disease agent.
      Borrelia burgdorferi, has provided protection to mice and other animals against
      systemic infection when delivered orally as a recombinant protein in Escherichia
      coli, bacille Calmette. Guerin or Salmonella typhimurium. In the present study
      purified recombinant strain B31 OspA or outer surface protein D (OspD), another
      lipoprotein of B. burgdorferi, were administered either subcutaneously (s.c.) or
      orally without cell carrier or adjuvant to mice. In comparison to the OspD
      preparation, the OspA protein was 256-fold more resistant to trypsin. Whereas
      OspA in the suspension was in regular complexes of 17-25 nm in size, OspD formed
      amorphous globules of different sizes. Animals received a primary immunization
      and at least one booster. Mice immunized s.c. with either OspA or OspD had
      detectable antibodies to B. burgdorferi by enzyme-linked immunosorbent assay
      (ELISA), growth inhibition assay (GIA) and immunoblot. Delivered orally, OspA but
      not OspD elicited a specific antibody response, including IgA, as determined by
      these assays. The geometric mean titre of sera from mice who received 4
      micrograms of OspA orally on days 1, 2, 4, 21 and 22 was 1470 by Ig ELISA, 320 by
      IgA ELISA and 128 by GIA. In infectious challenge experiments with B. burgdorferi
      strain Sh2-2-82 (OspA+ OspD- ) inoculated intradermally at 100 x the ID 50 all
      eight mice immunized with the 4 micrograms dose of OspA were protected, none of
      the mice immunized with the 4 micrograms dose of OspD were protected (P < 0.001
      by Fisher exact test). These studies indicate that the lipoprotein OspA provides
      protection against systemic B. burgdorferi infection when delivered orally as a
      purified protein.

PMID- 9178477
TI  - Immunity status against poliomyelitis in persons 13-14 years old living in Rome.
AB  - The immunity against poliomyelitis in 1000 subjects 13-14 years old was
      evaluated. Neutralizing antibodies against poliovirus type 1, 2 and 3 were
      detected in 97.6%, 95.8% and 70% of samples, respectively. 3/1000 (0.3%) subjects
      were simultaneously seronegative to the three types. WHO does not suggest a
      protective level of International Units (IU), but our data indicate that such
      level is 0.45 IU for polio type 1, 0.65 IU for the type 2 and 0.138 for the type
      3. A booster dose of vaccine in adolescence to ensure personal and herd immunity
      is recommended.

PMID- 9178478
TI  - Recombinant Opc meningococcal protein, folded in vitro, elicits bactericidal
      antibodies after immunization.
AB  - The meningococcal Opc protein has been expressed as inclusion bodies in
      Escherichia coli. After cell disruption and successive washing of the insoluble
      fraction, insoluble proteins were solubilized in presence of the chaotropic agent
      guanidium hydrochloride. The extract was applied to a Reverse Phase High
      Performance Liquid Chromatography (RP-HPLC)-C4 column, for further purification.
      The obtained recombinant Opc protein was refolded in vitro, by the addition of
      several compounds to the resuspended solution. Over time, the progress of
      renaturation was tested by immunoblot with the human monoclonal antibody LuNm03
      against the meningococcal Opc protein. LuNm03 recognizes a conformational epitope
      on the native meningococcal Opc protein. Having established the optimal
      conditions of renaturation. Balb/c mice were immunized to study the humoral
      immune response. The human at immune response elicited in mice was measured by
      ELISA and immunoblot, while the functional activity of these antibodies was
      assayed in a bactericidal test. According to our results, it was possible to
      obtain a recombinant Opc protein folded in vitro, with a conformation suitable
      enough to generate functional antibodies in mice, capable of killing meningococci
      in the presence of human complement.

PMID- 9178479
TI  - Diversified prime and boost protocols using recombinant vaccinia virus and
      recombinant non-replicating avian pox virus to enhance T-cell immunity and
      antitumor responses.
AB  - Recombinant vaccinia viruses containing tumor associated genes represent an
      attractive vector to induce immune responses to weak immunogens in cancer
      immunotherapy protocols. The property of intense immunogenicity of vaccinia
      proteins, however, also serves to limit the number of inoculations of recombinant
      vaccinia viruses. Host immune responses to the first immunization have been shown
      to limit the replication of subsequent vaccinations and thus reduce effectiveness
      of boost inoculations. The use of recombinant avian pox viruses (avipox) such as
      the canarypox (ALVAC) or fowlpox are potential candidates for immunization
      protocols in that they can infect mammalian cells and express the inserted
      transgene, but do not replicate in mammalian cells. We report here the
      construction and characterization of a canarypox (ALVAC) recombinant expressing
      the human carcinoembryonic antigen (CEA) gene (designated ALVAC-CEA). Antibody,
      lymphoproliferative and cytolytic T-cell responses as well as tumor inhibition
      were shown to be elicited by the ALVAC-CEA recombinant in a murine model. The
      utilization of a diversified immunization scheme using a recombinant vaccinia
      virus followed by recombinant avian pox virus was shown to be far superior than
      the use of either one alone in eliciting CEA-specific T-cell responses.
      Experiments were conducted to determine if the use of a diversified immunization
      scheme using a recombinant vaccinia virus (rV-CEA) and ALVAC-CEA would be
      superior to the use of either one alone in eliciting CEA-specific T-cell
      responses. When mice were immunized with rV-CEA and then ALVAC-CEA. CEA-specific
      T-cell responses were at least four times greater, and for superior to those
      achieved with three immunizations of ALVAC-CEA. Multiple boosts of ALVAC-CEA
      following rV-CEA immunization further potentiated anti-tumor effects and CEA
      specific T-cell responses. These studies demonstrate the proof of concept of the
      advantage of diversified immunization protocols employing both recombinant
      vaccinia and recombinant avipox vectors.

PMID- 9178480
TI  - Integration of hepatitis B vaccination into the expanded programme on
      immunization in Chonburi and Chiangmai provinces, Thailand.
AB  - Hepatitis B (HB) immunization was introduced as part of the expanded programme on
      immunization (EPI) in two provinces in Thailand and evaluated over a four year
      period. Three doses of HB vaccine were offered to 60,980 newborns at birth, 2 and
      6 months of age. The overall coverage for complete HB immunization was 90.4%.
      Serosurveys of randomly selected children under the age of 5 years were
      undertaken before and at the end of the project. Levels of HBsAg positivity were
      reduced by 85%, and there was a corresponding 70% increase in protective
      immunity. These findings demonstrate that HB immunization can be successfully
      integrated into EPI without adverse effect on coverage rates of other antigens,
      and results in a marked reduction in the rate of chronic carriage of HB virus in
      preschool age children.

PMID- 9178481
TI  - Immunogenicity and safety of Haemophilus influenzae type b polysaccharide
      Neisseria meningitidis conjugate vaccine in 7.5 micrograms liquid formulation: a
      comparison of three lots with the 15.0 micrograms lyophilized formulation. Study
      Group for 7.5 micrograms Liquid PedvaxHIB.
AB  - We conducted a multicenter, single-blind, randomized comparisons of the
      immunogenicity and safety of three manufacturing-scale lots of 7.5 micrograms
      liquid Haemophilus influenzae type b polysaccharide- Neisseria meningitidis
      conjugate vaccine (PRP-OMPC) and a single lot of 15.0 micrograms lyophilized PRP
      OMPC. A total of 908 infants were entered into the study. Each infant received
      two primary injections intramuscularly 2 months apart beginning at age 2-6 months
      and a booster injection at 12-15 months. Blood samples for serology were obtained
      before each injection and 1 month after the second and the booster dose. Immune
      responses were measured by radioimmunoassay. Approximately 80% of the infants
      achieved a titer > 1.0 micrograms ml-1 after the second primary dose of all four
      lots tested: the geometric mean titer (GMT) was ca 3 micrograms ml-1 for each
      vaccine group. After the booster dose, more than 90% of infants from each vaccine
      group had a titer > 1.0 microgram ml-1;GMTs ranged from 8 to 10 micrograms ml-1.
      No serious vaccine-associated adverse reactions were reported. Thus the 7.5
      liquid PRP OMPC vaccine was at least as immunogenic and well tolerated as the
      15.0 micrograms lyophilized vaccine.

PMID- 9178482
TI  - Chronic and recovered cases of sheep-associated malignant catarrhal fever in
      cattle.
AB  - Malignant catarrhal fever (MCF) is traditionally regarded as a disease with a
      short clinical course, low morbidity and high case fatality rate. Owing to the
      limitations of the assays used for laboratory diagnosis. It was difficult in
      characterise the clinical spectrum of sheep-associated MCF, particularly when the
      cattle recovered from an MCF-like clinical syndrome. Over a period of three
      years, 11 cattle that survived MCF for up to two-and-a-half years were identified
      on four premises. A clinical diagnosis of MCF was confirmed by the detection of
      ovine herpesvirus-2 DNA in peripheral blood leucocytes using a polymerase chain
      reaction (PCR) assay that detects a specific 238 base-pair fragment of viral
      genomic DNA. Of the 11 cattle examined, six recovered clinically with the
      exception of bilateral corneal oedema with stromal keratitis (four animals) and
      unilateral perforating keratitis (one animal). The 10 animals available for
      postmortem examination had disseminated subacute to chronic arteriopathy.
      Recovery was associated with the resolution of the acute lymphoid panarteritis
      that characterises the acute phase of MCF, and with the development of
      generalised chronic obliterative arteriosclerosis. Bilateral leucomata were due
      in part to the focal destruction of corneal endothelium secondary to acute
      endothelialitis. Formalin-fixed tissues and/or unfixed lymphoid cells from all 11
      cattle were positive for sheep-associated MCF by PCR. These observations indicate
      that recovery and chronic disease are a significant part of the clinical spectrum
      of MCF and that such cases occur with some frequency in the area studied. The
      affected cattle remain persistently infected by the putative sheep-associated MCF
      gammaherpesvirus.

PMID- 9178484
TI  - Surgical treatment of a septic dentigerous cyst in a goat.
AB  - A slowly growing lesion of the rostral mandible of a goat was diagnosed to be a
      septic dentigerous cyst. The lesion was treated surgically to remove one
      displaced tooth and debride the cystic cavity, and systemic antibiotic therapy
      was applied. Thirty-four weeks later the goat was clinically and radiographically
      improved and the problem had not recurred.

PMID- 9178483
TI  - Comparison of standardbred trotters exercising on a treadmill and a race track
      with identical draught resistances.
AB  - The responses in heart rate, plasma lactate and rectal temperature of
      standardbred trotters to draught loaded interval exercise on a treadmill and a
      race track were studied. The horses were exercised with incrementally increasing
      trotting speeds for two-minute intervals with draught loads of 10, 20 and 30
      kilopond (kp) in three different tests. Each trotting interval was followed by
      two-minute periods at a walk without a draught load. Measurements of heart rate
      and plasma lactate were made at the end of each interval and the rectal
      temperature was taken at the end of the exercise. The heart rate and plasma
      lactate levels were significantly lower on the treadmill than on the track in the
      tests with 10 kp, but no significant differences were found between the treadmill
      and track exercise tests with the heavier draught resistances. No differences
      were observed in rectal temperature between treadmill and track conditions. From
      these findings it was concluded that the workload was significantly greater on
      the race track compared to the treadmill when the draught resistance was low (10
      kp). Although the workload increased on both the race track and the treadmill as
      draught resistance increased, at the heavier draught resistances track exercise
      was no longer more demanding than exercise on the treadmill.

PMID- 9178485
TI  - Hypophosphataemic rickets and nephrocalcinosis in ostrich chicks brooded and
      reared on limestone sand.

PMID- 9178486
TI  - Pituitary and ovarian response to PMSG and GnRH of a gonadal dysgenetic buffalo.

PMID- 9178487
TI  - Use of frontline spray on rabbits.

PMID- 9178489
TI  - Integration of women into the profession.

PMID- 9178488
TI  - Neural tissue embolism in cattle.

PMID- 9178490
TI  - Frozen tail or limber tail in working dogs.

PMID- 9178491
TI  - The TATA-less promoter of hepatitis B virus S gene contains a TBP binding site
      and an active initiator.
AB  - The surface antigen (S) gene promoter, one of the major hepatitis B virus (HBV)
      promoters, directs the synthesis of a 2.1 kb mRNA which encodes the preS2 and S
      polypeptides. The preS2/S promoter does not contain a classical TATA box, and
      transcription regulation of the preS2/S gene has not been fully elucidated. We
      analysed two regions involved in preS2/S gene transcription of the HBV adw
      subtype: the diverged TATA box and a putative initiator element. We demonstrated
      sequence specific promoter activity of the putative TATA-like sequences in the
      preS2/S gene promoter (-25 to -32 bp). Using end labeled synthetic
      oligonucleotides we observed specific binding of nuclear extracts to the diverged
      TATA sequence, that was significantly reduced using a mutated oligonucleotide.
      Specific binding of yeast TBP to the diverged TATA sequence was shown which was
      increased in the mutant containing a classical TATA box. We analysed the proposed
      initiator (Inr) sequence of the preS2/S promoter region (-13 to -16 bp). Deletion
      of the inr element markedly reduced promoter activity as assessed by CAT
      expression. Gel shift assays showed specific binding of nuclear extracts to wild
      type but not to mutant Inr. Expression studies with double mutants of the
      diverged TATA and the Inr element established that both elements are active in
      transcription regulation.

PMID- 9178492
TI  - Phosphorylation of tick-borne encephalitis virus NS5 protein.
AB  - The largest tick-borne encephalitis virus (TBEV) non-structural protein NS5 (100
      kDa) is believed to be involved in RNA replication. The protein is phosphorylated
      in infected cell extracts in the presence of [gamma-32P]ATP, as shown by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot
      analysis using monoclonal antibodies raised against TBEV NS5 protein. Radioactive
      labeling of NS5 in cellular extracts at an early stage post-infection is higher
      than at 24 h post-infection. Incubation of immunoprecipitates of NS5 protein with
      [gamma-32P]ATP in the presence of Mg2+ resulted in the phosphorylation of TBEV
      NS5 protein and of immunoglobulins. Phosphoamino acid analysis demonstrated that
      NS5 contains phosphoserine, but not phosphothreonine, or phosphotyrosine.

PMID- 9178493
TI  - Towards defining a minimal functional domain for NTPase and RNA helicase
      activities of the hepatitis C virus NS3 protein.
AB  - Hepatitis C virus (HCV) possesses two separate enzymatic functions in the NS3
      protein: a protease and an NTPase/RNA helicase. In order to determine the minimal
      domain for NTPase and RNA helicase activities of the HCV NS3 protein, serial
      deletion mutants were constructed. The NS3H protein a fusion protein of 25 amino
      acids (aa) from an expression vector and the C-terminal 466 aa of the HCV NS3
      protein, contains an NTPase/RNA helicase activity. We made deletion mutants of
      10, 30, 50, 97, and 135 aa from the C-terminus and 16 and 32 aa from the N
      terminus of the NS3H protein. The deleted protein lacking 50 aa from the C
      terminus still possessed both activities, while the protein lacking 97 aa from
      the C-terminus lost an RNA helicase activity. The mutant lacking 16 amino acids
      from the N-terminus retained the enzymatic activities and the N-terminal 32 aa
      deleted mutant lost an NTPase/RNA helicase activity. A combinational deletion
      mutant lacking 16 aa the N-terminus and 50 aa from the C-terminus retained the
      enzymatic activities. These results show that the functional domain of the HCV
      NTPase/ RNA helicase is about 400 aa in length and maps between NS3 residues 1209
      and 1608.

PMID- 9178494
TI  - Complete sequence of two tick-borne flaviviruses isolated from Siberia and the
      UK: analysis and significance of the 5' and 3'-UTRs.
AB  - The complete nucleotide sequence of two tick-transmitted flaviviruses,
      Vasilchenko (Vs) from Siberia and louping ill (LI) from the UK, have been
      determined. The genomes were respectively, 10928 and 10871 nucleotides (nt) in
      length. The coding strategy and functional protein sequence motifs of tick-borne
      flaviviruses are presented in both Vs and LI viruses. The phylogenies based on
      maximum likelihood, maximum parsimony and distance analysis of the polyproteins,
      identified Vs virus as a member of the tick-borne encephalitis virus subgroup
      within the tick-borne serocomplex, genus Flavivirus, family Flaviviridae.
      Comparative alignment of the 3'-untranslated regions revealed deletions of
      different lengths essentially at the same position downstream of the stop codon
      for all tick-borne viruses. Two direct 27 nucleotide repeats at the 3'-end were
      found only for Vs and LI virus. Immediately following the deletions a region of
      332-334 nt with relatively conserved primary structure (67-94% identity) was
      observed at the 3'-non-coding end of the virus genome. Pairwise comparisons of
      the nucleotide sequence data revealed similar levels of variation between the
      coding region, and the 5' and 3'-termini of the genome, implying an equivalent
      strong selective control for translated and untranslated regions. Indeed the
      predicted folding of the 5' and 3'-untranslated regions revealed patterns of stem
      and loop structures conserved for all tick-borne flaviviruses suggesting a
      purifying selection for preservation of essential RNA secondary structures which
      could be involved in translational control and replication. The possible
      implications of these findings are discussed.

PMID- 9178495
TI  - Production of active polyomavirus large T antigen in yeast Pichia pastoris.
AB  - The coding region of polyomavirus large T antigen was engineered into the genome
      of the methylotrophic yeast Pichia pastoris by use of the vector pHIL-D2.
      Expression of large T antigen was induced by methanol under the control of the
      strong alcohol oxidase (AOX1) promoter. Large T antigen was purified by
      immunoaffinity chromatography. We showed that yeast-derived large T antigen bound
      specifically to a DNA fragment that contains the polyomavirus replication origin,
      protected the four known major binding sites in the origin against DNase I
      digestion, and could unwind the strands of an origin-containing DNA fragment in
      an ATP-dependent manner. This system therefore provides a convenient and
      inexpensive source of biologically active polyomavirus large T antigen for in
      vitro studies.

PMID- 9178496
TI  - Capsid protein composition of reference strains and wild isolates of human
      astroviruses.
AB  - Astroviruses are small RNA viruses that are frequently associated with
      gastroenteritis in humans and animals. Despite much work on the genetic analysis
      of astrovirus strains, little progress has been made in the characterization of
      the proteins composing mature virions. We have analyzed the capsid protein
      composition of the reference strains and several wild isolates of human
      astroviruses using high-resolution polyacrylamide gradient gels. For reference
      strains of the seven serotypes analyzed, a consistent pattern of three infection
      specific proteins--designated P1, P2, and P3 -was generally observed. The strains
      could be divided into two groups, based upon the reactivity of these proteins in
      immune precipitation assays that used homologous rabbit serum. One group included
      reference types 1 4 for which all three proteins were precipitated by homologous
      rabbit sera; for the other group, types 5 7, only proteins P2 and P3 were
      precipitated. When wild isolates from around the world were compared to the
      reference strains, a correlation between genetic type and the pattern of protein
      sizes and immune reactivity was observed for strains of the common types (1-4).
      Strains of types 2 and 4 consistently exhibited P3 proteins larger than those of
      types 1 and 3. Unusual patterns of proteins or immune reactivity were detected in
      strains of types 5-7, indicating that there may be incomplete processing of the
      capsid precursor during growth in cell culture.

PMID- 9178497
TI  - Multiplication of tomato spotted wilt virus in primary cell cultures derived from
      two thrips species.
AB  - Primary cell cultures prepared from embryos of the thrips species Frankliniella
      occidentalis and Thrips tabaci were tested for their potential to support
      replication of tomato spotted wilt virus (TSWV). Using polyclonal antibodies
      against the viral nucleocapsid protein (N) and indirect immunofluorescent
      staining, discrete spots with strong signals were observed in the cytoplasm at 48
      h post-inoculation in the cell cultures of a F. occidentalis, and a T. tabaci
      population which failed to transmit the virus. The infection was found in
      approximately 40% of the monolayer cells. Using antibodies against a
      nonstructural protein (NSs) of TSWV, uniform and more diffused staining was
      observed throughout the cytoplasm of these cells, underlying active genome
      replication. The NSs protein accumulated slower than the N protein in the cells
      of both thrips species. No multiplication of TSWV was observed in a heterologous
      insect cell line, i.e. from Spodoptera frugiperda, suggesting the existence of
      specific host factors in the thrips-derived cells.

PMID- 9178498
TI  - Genetically variable triplet repeats in a RING-finger ORF of Helicoverpa species
      baculoviruses.
AB  - Nucleotide sequence analysis of the Helicoverpa zea S-type nucleopolyhedrovirus
      (HzSNPV) genomic interval between the polh and iel genes has revealed an open
      reading frame (HOAR ORF) that contains a complex A 1-T rich triplet repeat region
      (RAT-repeats). HOAR ORF is predicted to encode an acidic, arginine residue rich.
      712 aa protein, with a C3HC4 (RING-finger) zinc binding motif. RAT-repeats,
      distributed over 450 bp. consist of GAT. AAT, and GTT codons, correspond to Asp,
      Asn and Val residues which display an extreme codon bias not seen with nine other
      genes of this virus. A survey of four other (field) isolates of Helicoverpa sp.
      NPVs confirms a high incidence of mutation in the RAT-repeat region. A 158-bp
      conserved block, homologous to the pe38-ien promoter of AcMNPV, was identified
      upstream of HOAR ORF. The sub-region of the genome in which HOAR ORF is located
      is susceptible to rearrangement.

PMID- 9178499
TI  - Characterization of arenaviruses using a family-specific primer set for RT-PCR
      amplification and RFLP analysis. Its potential use for detection of
      uncharacterized arenaviruses.
AB  - Arenaviruses are enveloped viruses with a genome composed of two ssRNA species,
      designated L and S. The arenaviruses were divided in two major groups (Old World
      and New World), based on serological properties and genetic data, as well as
      geographic distribution. A sequence alignment analysis of all reported arenavirus
      S RNAs yielded 17 conserved regions in addition to a reported conserved region at
      the end of both RNAs. The consensus sequences of these regions were used to
      design generalized primers suitable for RT-PCR amplification of a set of
      overlapping nucleotide sequence fragments comprising the complete S RNA of any
      arenavirus. A restriction analysis (RFLP) was designed to rapidly typify the
      amplified fragments. This RT-PCR-RFLP approach was tested with Old World (LCM)
      and New World (Junin and Tacaribe) arenaviruses. Furthermore, using this
      procedure the whole S RNA of a novel arenavirus isolate obtained from a rodent
      trapped in central Argentina, was amplified and characterized. Partial nucleotide
      sequence data were used for phylogenetic analyses that showed the relationships
      between this arenavirus and the rest of the members of the family. This
      relatively simple methodology will be useful both in basic studies and
      epidemiological survey programs.

PMID- 9178500
TI  - Evidence for the assignment of two strains of SPLV to the genus Potyvirus based
      on coat protein and 3' non-coding region sequence data.
AB  - The use of potyvirus-specific primers and subsequent application of the RACE
      procedure allowed the cloning of the 3' terminal 1088 nucleotides of the genomic
      RNA of the Taiwan isolate of sweetpotato latent virus (SPLV-T) and the 3' genomic
      1085 nucleotides of a SPLV-like virus from China (SPLV-CH). The sequence of an
      internal part of the presumptive nuclear inclusion b gene was also determined for
      both isolates. Detailed sequence analyses revealed the presence of consensus
      motifs which indicated that SPLV-CH and SPLV-T should be regarded as members of
      the genus Potyvirus. Multiple sequence alignments and phylogenetic analyses were
      also performed and unambiguously assessed these isolates as strains of a distinct
      Potyvirus. SPLV was not related to other potyviruses infecting sweetpotato nor to
      any other sequenced virus. From the presence of the DAG box, SPLV-CH is expected
      to be a typical aphid transmitted Potyvirus whereas a conceivable explanation is
      proposed for the non-aphid transmission of SPLV-T.

PMID- 9178501
TI  - Induction of apoptosis and cleavage of poly(ADP-ribose) polymerase by cytopathic
      bovine viral diarrhea virus infection.
AB  - The Pestivirus bovine viral diarrhea virus (BVDV) causes the fatal diarrheal
      syndrome, mucosal disease, because of mutations in the viral genome which convert
      the common noncytopathic (ncp) BVDV into a cytopathic (cp) biotype. We examined
      the nature of the cytopathic effect of cp-BVDV in cultured bovine cells in order
      to accurately describe the process and to gain insight into the mechanism of cp
      BVDV-induced cell death. The findings demonstrate that cells infected with cp
      BVDV in vitro die by apoptosis, but cells infected with ncp-BVDV do not. Analysis
      of nuclear morphology by staining with fluorescent DNA dye and cpi-fluorescence
      microscopy showed chromatin condensation and margination in cells infected with
      cp-BVDV. Transmission electron microscopy (TEM) confirmed the condensation of
      chromatin, as well as cell shrinkage and generation of apoptotic bodies. The
      chromosomal DNA of cells infected with cp-BVDV undergoes fragmentation,
      generating the typical oligonucleosomal fragments commonly noted during
      apoptosis. The fragmented DNA was released from the nucleus to the cytoplasm, and
      eventually to the culture supernatant. Infection with cp-BVDV activates cellular
      proteases of the ICE family leading to cleavage of poly(ADP-ribose) polymerase
      (PARP), a nuclear enzyme implicated in genome maintenance. This demonstration
      that cp-BVDV kills cells by triggering apoptosis suggests the possibility that cp
      BVDV is associated with a fatal disease by the acquisition of a new apoptosis
      inducing activity. We consider BVDV to be an excellent model system for studies
      of the biological and medical relevance of apoptosis in viral infections.

PMID- 9178502
TI  - Yarrowia lipolytica SRP54 homolog and translocation of Kar2p.
AB  - To investigate the role of Srp54p in protein translocation, the Yarrowia
      lipolytica SRP54 homolog was cloned. Sequencing revealed an open reading frame of
      536 amino acids coding for a 57.2 kilodalton polypeptide with 55 to 57% sequence
      identity to Srp54ps of Saccharomyces cerevisiae, Schizosaccharomyces pombe, and
      mouse. Like these Srp54ps, Y. lipolytica Srp54p has an N-terminal domain with a
      highly conserved GTP-binding site and a methionine-rich C-terminal domain.
      Differing results regarding the essentiality of SRP subunits were obtained. SRP54
      is important but not essential for growth, but it was reconfirmed that at least
      one SRP RNA gene is essential. Cells with SRP54 deleted grow about six times more
      slowly than wild type; faster-growing colonies, still growing much slower than
      wild type, appeared quite frequently. In srp54 delta cells, no untranslocated
      alkaline extracellular protease precursor was detected. Therefore, to develop
      another reporter molecule the Y. lipolytica KAR2 homolog was cloned and Kar2p
      antibodies were produced. For Kar2p an untranslocated precursor was detected in
      srp54 delta but not in wild-type cells, suggesting that its translocation was
      defective in the srp54 delta cells. These results confirm an in vivo rule for SRP
      in protein translocation in Y. lipolytica, suggest that SRP RNA or an SRP core
      particle has functions not shared by Srp54p, and show that, as in S. cerevisiae
      and Sz. pombe, reporter molecules differ in their dependency on SRP for
      translocation.

PMID- 9178503
TI  - Mechanisms of salt tolerance conferred by overexpression of the HAL1 gene in
      Saccharomyces cerevisiae.
AB  - Overexpression of the HAL1 gene improves the tolerance of Saccharomyces
      cerevisiae to NaCl by increasing intracellular K+ and decreasing intracellular
      Na+. The effect of HAL1 on intracellular Na+ was mediated by the PMR2/ENA1 gene,
      corresponding to a major Na+ efflux system. The expression level of ENA1 was
      dependent on the gene dosage of HAL1 and overexpression of HAL1 suppressed the
      salt sensitivity of null mutants in calcineurin and Hal3p, other known regulators
      of ENA1 expression. The effect of HAL1 on intracellular K+ was independent of the
      TRK1 and TOK1 genes, corresponding to a major K+ uptake system and to a K+ efflux
      system activated by depolarization, respectively. Overexpression of HAL1 reduces
      K+ loss from the cells upon salt stress, a phenomenon mediated by an unidentified
      K+ efflux system. Overexpression of HAL1 did not increase NaCl tolerance in
      galactose medium. NaCl poses two types of stress, osmotic and ionic, counteracted
      by glycerol synthesis and sodium extrusion, respectively. As compared to glucose,
      with galactose as carbon source glycerol synthesis is reduced and the expression
      of ENA1 is increased. As a consequence, osmotic adjustment through
      glycerolsynthesis, a process not affected by HAL1, is the limiting factor for
      growth on galactose under NaCl stressed.

PMID- 9178504
TI  - The osmotic hypersensitivity of the yeast Saccharomyces cerevisiae is strain and
      growth media dependent: quantitative aspects of the phenomenon.
AB  - Osmotic hypersensitivity is manifested as cellular death at magnitudes of osmotic
      stress that can support growth. Cellular capacity for survival when plated onto
      high NaCl media was examined for a number of laboratory and industrial strains of
      Saccharomyces cerevisiae. During respiro-fermentative growth in rich medium with
      glucose as energy and carbon source, the hypersensitivity phenomenon was fairly
      strain invariant with a threshold value of about 1 M-NaCl; most strains fell
      within a 300 mM range in LD10 values (lethal dose yielding 10% survival).
      Furthermore, all but one of the strains displayed similar differential death
      responses above the threshold value, i.e. ten-fold decreased viability for every
      250 mM increase in salinity. Addition of small amounts of salt to the growth
      medium drastically improved tolerance and shifted the hypersensitivity threshold
      to higher NaCl concentrations. This salt-instigated tolerance could partly be
      reversed by washing in water. The washing procedure depleted cells of the
      glycerol that they had accumulated under saline growth, and the contribution from
      glycerol to the improved tolerance was about 50% in the two strains examined.
      Growth on derepressing carbon sources like galactose, ethanol or glycerol gave
      strain-dependent responses. The laboratory strain X2180-1A drastically improved
      tolerance while the bakers' yeast strain Y41 did so only marginally. It was
      concluded that all strains of S. cerevisiae display the osmotic hypersensitivity
      phenomenon in qualitative terms while the quantitative values differ. It was also
      proposed that growth rate does not dictate the level of osmotic hypersensitivity
      of S. cerevisiae.

PMID- 9178505
TI  - Role of the cytoskeleton in endocytosis of the yeast maltose transporter.
AB  - Certain components of the cytoskeleton play a role in yeast fluid-phase
      endocytosis as well as in endocytosis of the alpha-factor when this pheromone is
      bound to its 7-transmembrane segment receptor. The yeast maltose transporter is a
      12-transmembrane segment protein that, under certain physiological conditions, is
      degraded in the vacuole after internalization by endocytosis. In this work, the
      possible role of the cytoskeleton in endocytosis of this transporter has been
      investigated. Using mutants defective in beta-tubulin, actin and the actin
      binding proteins Sac6 and Abp85. as well as nocodazole, which inhibits formation
      of microtubules, we have shown that actin microfilaments are involved in
      endocytosis of the maltose transporter whereas microtubules are not.

PMID- 9178506
TI  - Expression cassettes for formaldehyde and fluoroacetate resistance, two dominant
      markers in Saccharomyces cerevisiae.
AB  - We employed two genes in constructing yeast expression cassettes for dominant,
      selectable markers. The Saccharomyces cerevisiae gene SFA1, encoding formaldehyde
      dehydrogenase, was placed under the control of the GPD1 promoter and CYC1
      terminator. The Moraxella sp. strain B gene dehH1, encoding fluoroacetate
      dehalogenase, was placed under the control of both the GPD1 and CYC1 promoters.
      With these constructs it was possible to select directly for yeast strains
      resistant to either formaldehyde or fluoroacetate. Both selective agents are
      completely metabolized and inexpensive, making them very useful in the pursuit of
      yeast gene functions and for industrial applications. An additional advantage of
      the formaldehyde dehydrogenase marker is that it is an S. cerevisiae gene, thus
      allowing 'all yeast' constructs.

PMID- 9178507
TI  - Characterization of the Saccharomyces cerevisiae cdc42-1ts allele and new
      temperature-conditional-lethal cdc42 alleles.
AB  - Cdc42p is a highly conserved GTPase involved in controlling cell polarity and
      polarizing the actin cytoskeleton. The CDC42 gene was first identified by the
      temperature-sensitive cell-division-cycle mutant cdc42-1ts in Saccharomyces
      cerevisiae. We have determined the DNA and predicted amino-acid sequence of the
      cdc42-1ts allele and identified multiple mutations in the coding region and 5'
      promoter region, thereby limiting its usefulness in genetic screens. Therefore,
      we generated additional temperature-conditional-lethal alleles in highly
      conserved amino-acid residues of both S. cerevisiae and Schizosaccharomyces pombe
      Cdc42p. The cdc42W97R temperature-sensitive allele in S. cerevisiae displayed the
      same cell-division-cycle arrest phenotype (large, round unbudded cells) as the
      cdc42-1ts mutant. However, it exhibited a bud-site selection defect and abnormal
      bud morphologies at the permissive temperature of 23 degrees C. These phenotypes
      suggest that Cdc42p functions in bud-site selection early in the morphogenetic
      process and also in polarizing growth patterns leading to proper bud
      morphogenesis later in the process. In S. pombe, the cdc42W97R mutant displayed a
      cold-sensitive, los-of-function phenotype when expressed from the thiamine
      repressible nmt1 promoter under repressing conditions. In addition, cdc42T58A and
      cdc42S71P mutants showed a temperature-sensitive loss-of-function phenotype when
      expressed in S. pombe: these mutants did not display a conditional phenotype when
      expressed in S. cerevisiae. These new conditional-lethal cdc42 alleles will be
      important reagents for the further dissection of the cell polarity pathway in
      both yeasts.

PMID- 9178508
TI  - Phylogenetic classification of the mitochondrial carrier family of Saccharomyces
      cerevisiae.
AB  - The screening of the open reading frames identified in the whole yeast genome has
      allowed us to discover 34 proteins belonging to the mitochondrial carrier family.
      By phylogenetic study, they can be divided into 27 subfamilies including ADP/ATP,
      phosphate and citrate carriers, putative oxoglutarate and GDC carriers and 22 new
      subfamilies. Topology predictions using the 'positive inside rule' approach have
      shown that the yeast carriers are similarly oriented with both extremities
      exposed to the cytosol. In each subfamily, a strict conservation of the charged
      residues in the six transmembrane alpha-helices is observed, suggesting a
      functional role for these residues and the existence of 27 functionally distinct
      carriers.

PMID- 9178510
TI  - Current awareness on yeast.

PMID- 9178509
TI  - Sequence analysis of a 33.2 kb segment from the left arm of yeast chromosome XV
      reveals eight known genes and ten new open reading frames including homologues of
      ABC transporters, inositol phosphatases and human expressed sequence tags.
AB  - The complete nucleotide sequence of a 33221 bp segment, contained in cosmid
      pEOA1044, derived from the left arm of chromosome XV of Saccharomyces cerevisiae,
      appears in public databases between coordinates 177013 and 210234
      (http://speedy.mips.biochem.mpg.de/). Computer analysis of that sequence revealed
      the presence of the previously known genes IRA2, DEC1, NUF2, HST1, RTG1, RIB2 and
      HAL2, one previously partially sequenced open reading frame (ORF) of unknown
      function (SCORFAC) and ten newly identified ORFs. One of the new ORFs is similar
      to the Drosophila melanogaster white gene and other transmembrane ABC
      transporters, another one has similarities to inositol phosphatases and others
      are similar to ORFs of unknown function from various organisms, including human
      Expressed Sequence Tags (ESTs). Potential transmembrane regions, ATP/GTP-binding
      and WD motifs have also been identified. The existence of yeast ESTs for two of
      the newly identified ORFs indicates that they are transcribed.

PMID- 9178511
TI  - Diel activity of Ixodes ricinus Acari:ixodidae at two locations near Stockholm,
      Sweden.
AB  - The diel 'activity', i.e. availability, of Ixodes ricinus larvae, nymphs and
      adults was investigated in a meadow and a forest habitat near Stockholm during
      1991-1993. Generally, the immature ticks were more prevalent in the forest than
      in the meadow. In the meadow, the mean larval and adult numbers varied
      significantly between 4 h time intervals with the peak activity from 2300 to 0300
      h. In the forest, the tick numbers did not differ significantly between the time
      intervals. The association of the tick activity with certain meteorological
      variables was strongest in the meadow, where the mean numbers of all tick stages
      were negatively correlated with the temperature. The relative humidity was
      positively correlated only with the mean numbers of larvae. In contrast, the
      larval activity in the forest was positively and negatively correlated with the
      temperature and relative humidity, respectively, while the nymphal and adult
      activity showed no association with these climatic variables. The impact of the
      host activity on the tick diel activity is also discussed.

PMID- 9178512
TI  - A new type of hydrophilic carbon paste electrodes for biosensor manufacturing:
      binder paste electrodes.
AB  - The effect of two types of carbon pastes and two osmium-based redox mediators on
      the response of amperometric enzyme electrodes for glucose was examined. A
      hydrophobic mediator and a hydrophilic cationic mediator were prepared and mixed
      in a paste that contained either mineral oil as the pasting liquid, or a
      polycationic electrolyte without oil. It was found that the current densities
      were increased by a factor of 25 when the oil-based paste was replaced by the
      hydrophilic one (binder paste, BP) and five- to six-fold when the hydrophilic
      mediator was used in place of the hydrophobic. The linear range for the glucose
      oxidase electrodes was extended to concentrations higher than 60 mM. The glucose
      electrodes were preliminary optimized and their half-life time reached more than
      12 h when operated continuously under vigorous stirring when the 'pasting'
      polyelectrolyte was crosslinked. At a working potential of 400 mV versus the
      Ag/AgCl saturated electrode, the saturating current densities per geometric
      surface area were 1.2 mA/cm2 +/- 0.2 (n = 7). These 'binder paste electrodes' are
      the first reported bulk modified electrodes without hydrophobic pasting liquid or
      cover membranes, and present an interesting research and application tool.

PMID- 9178513
TI  - Electrochemiluminescence flow injection immunoassay for atrazine.
AB  - Antibodies to atrazine were labelled with glucose oxidase and used in
      colorimetric enzyme linked immunosorbent assays. Transparent aminosilanized
      indium tin oxide coated glass electrodes were derivatized with aminodextran
      covalently modified with atrazine caproic acid. The labelled antibodies were used
      to investigate the derivatized electrodes colorimetrically and the electrodes
      were use in an electrochemiluminescence flow injection analyser.
      Electrochemiluminescence immunoassay for atrazine in the range 0-10 ppb showed
      that it was possible to detect less than 0.1 ppb, the precautionary limit for
      pesticides in drinking water recommended by the European Commission.

PMID- 9178514
TI  - A cell-based immunobiosensor with engineered molecular recognition--Part I:
      Design feasibility.
AB  - A novel bioelectronic sensor is described in which living immune cells are
      transformed into unique biotransducer couples by engineering their molecular
      recognition for preselected antigens of clinical interest. This 'hybrid'
      biosensor, constructed with mast cells interfaced to a microfabricated
      thermoelectric device with the use of biomolecular linkages, is capable of
      detecting antigens in real time by transducing minute heat changes arising from
      antigen-induced mast cell activation processes. The thermoelectric approach was
      selected based upon preliminary bioenergetic calculations which indicated that
      metabolic changes arising from mast cell antigen recognition result in a
      significant increase in exothermic heat relative to basal metabolic conditions.
      Experimental studies confirmed that mast cell activation and degranulation can be
      discriminated theramally from basal metabolic activity. Results obtained from
      microcalorimetry experiments using cultured mast cells (MC/9) mucosal-like mast
      cell line), and harvested mast cells (rat peritoneal mast cells) indicated that
      detectable increases in heat output (-3 +/- 0.5 pW/cell, mean peak output)
      immediately followed cell activation. The construction of a miniature hybrid
      immunobiosensor device was made possible by bioelectronic coupling achieved with
      the use of cellular adhesive proteins that immobilized non-adherent (MC/9) cells
      as well as adherent (RBL-2H3 rat basophilic leukemia) cells to the thermopile.
      Results from preliminary tests conducted on a hybrid biosensor prototype
      validated the design feasibility of a miniature, living cell immunodiagnostic
      biosensor. Such cell-based hybrid biosensor approaches may greatly extend the
      capability for selective, rapid, on-site, antigen detection for a wide range of
      clinically relevant antigens and offer new approaches to in vitro diagnostics.

PMID- 9178515
TI  - Potential of microsensor-based feedback bioactuators for biophysical cancer
      treatment.
AB  - Solid tumors usually exhibit a poorly organized vascularization and a deviant
      energy metabolism which result in an acidic pH and large hypoxic areas in the
      tumor microenvironment. A lot of cell biological data support the hypothesis that
      such physico-chemical conditions are promoters of the microevolution of malignant
      cells, inhibitors of the immune response, and co-factors for tumor cell invasion.
      Our experimental in vitro analyses and computer simulations indicate that the
      efficiency of immunotherapies and classical methods for cancer treatment might be
      improved if a physico-chemical microenvironment could be restored which reflects
      that found in normal tissue. In order to monitor and manipulate the tumor
      microenvironment, we suggest utilizing silicon-based feedback bioactuators which
      are controlled by on-line microsensors. These miniaturized bioactuators play the
      role of 'pH clamps' and can be implanted directly at the sites of inoperable
      tumors and metastases where they can reconstitute normal physico-chemical
      conditions. The drug application scheme can be precisely controlled by an
      integrated microprocessor. The paper summarizes the current state of development
      of such microsensor-based feedback bioactuators and outlines their potential for
      biophysical cancer treatment.

PMID- 9178516
TI  - Continuous monitoring of L-glutamate released from cultured nerve cells by an
      online sensor coupled with micro-capillary sampling.
AB  - A small volume L-glutamate online sensor was developed in order to monitor
      changes in the local concentration of L-glutamate released from cultured nerve
      cells. Syringe pump in the suction mode is used to sample extracellular fluid
      continuously from a glass micro-capillary and the concentration of L-glutamate
      can be determined by using a glassy carbon (GC) electrode modified with an Os
      polyvinylpyridine mediator bottom film containing horseradish peroxidase and a
      bovine serum albumin top layer containing L-glutamate oxidase. The overall
      efficiency of L-glutamate detection with a sensor is 71% under optimum conditions
      due to an efficient enzymatic reaction at the modified electrode in the thin
      layer radial flow cell. As a result, we achieved a detection limit of 7-15 nM and
      a linear range of 50 nM to 10 microM. In an in vitro experiment, the
      extracellular fluid near a particular nerve cell can be sampled with this micro
      pipet and continuously introduced into the modified GC electrode in the radial
      flow cell via suction provided by a syringe pump. The nerve cells are stimulated
      by the KCl in a glass capillary and the L-glutamate concentration change can be
      monitored by changing the distance between the sampling pipet and the nerve
      cells.

PMID- 9178517
TI  - Voltammetric enzyme sensor for urea using mercaptohydroquinone-modified gold
      electrode as the base transducer.
AB  - A voltammetric urea-sensing electrode was prepared by combining a lipid-attached
      urease layer with a 2,5-dihydroxythiophenol-modified gold electrode. A self
      assembled monolayer of dihydroxythiophenol was prepared on the gold surface by
      soaking the electrode into an ethanolic solution containing the modifier. A layer
      of the lipid-attached enzyme and that of acetyl cellulose overcoat were
      successively made on the dihydroxythiophenol-modified electrode by applying a dip
      coating procedure. The addition of urea in a test solution (10 mM phosphate
      buffer, pH 7.0) brought about an increase of pH near the urease layer. The pH
      shift accompanied a negative shift of the anodic peak, which corresponded to the
      electro-oxidation of dihydroxyphenol moiety to form quinone, on the linear sweep
      voltammograms for the urease/dihydroxythiophenol electrode. The concentration of
      urea (0.2-5 mM) could be determined by measuring the electrode current at -0.05 V
      versus Ag/AgCl from the voltammogram. The electrode was applied to the
      determination of urea in human urine; the measurement of electrode current at
      such a low potential provided the urea determination without any electrochemical
      interference from L-ascorbic acid and uric acid.

PMID- 9178518
TI  - Effectiveness of protein A for antibody immobilization for a fiber optic
      biosensor.
AB  - The fiber optic biosensor performs fluoroimmunoassays at the surface of multimode
      optical fibers. The effectiveness of protein A, an immunoglobulin binding
      protein, for antibody immobilization on the surface of these fiber probes has
      been investigated. No difference was observed in the binding of fluorescently
      labeled goat-IgG by rabbit anti-goat IgG regardless of whether the capture
      antibody was bound to the probe surface via protein A or covalently attached.
      However, in a sandwich immunoassay for the F1 antigen of Yersinia pestis, probes
      with rabbit anti-plague IgG bound to the surface via protein A generated twice
      the signal as probes with the antibody covalently attached. Assay regeneration
      was also examined with protein A probes since antibody-antigen complexes have
      been successfully eluted from protein A under low pH conditions. Protein A probes
      coated with rabbit anti-goat IgG obtained nearly identical signal levels at 500
      and 5000 ng/ml of Cy5.5 goat IgG five consecutive times following regeneration
      with glycine-HCl, 2% acetic acid, pH 2.5.

PMID- 9178519
TI  - Indonesian medicinal plants. XIX. 1) Chemical structures of four additional resin
      glycosides, mammosides A, B, H1, and H2, from the tuber of Merremia mammosa
      (Convolvulaceae).
AB  - Four new resin-glycosides, named mammosides A (10), B (11), H1 (12), and H2 (13),
      were isolated from the tuber of Merremia mammosa (Convolvulaceae), a Jamu raw
      material. Their chemical structures have been elucidated on the bases of chemical
      and physicochemical evidence, including synthesis of a glycosidic acid designated
      as mammoside I.

PMID- 9178520
TI  - Simple approach to optically active drimane sesquiterpenes based on enzymatic
      resolution.
AB  - When the beta-acyloxy esters (+/-)-10 and (+/-)-11 were exposed to the lipase OF
      360 from Candida rugosa or immobilized lipase OF-360 in a water-saturated organic
      solvent, the hydrolyzed product (8aS)-6 was obtained in high chemical (40%) and
      optical (> 99% ee) yields. The absolute structure of (8aS)-6 was confirmed by the
      fact that (8aS)-6 was converted into an authentic sample gamma-keto nitrile (8aS)
      17. Treatment of the diol (+/-)-12 with isopropenyl acetate in the presence of
      the lipase Godo E-4 from Pseudomonas sp. provided the unchanged (8aR)-12 (89% ee)
      in 42% yield.

PMID- 9178521
TI  - Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and
      structure-activity relationships of a series of cyproheptadine analogues.
AB  - Cyproheptadine is a drug that shows high affinity for type 2 (5-HT2) receptors.
      We studied a series of compounds obtained by modification of the tricyclic system
      of Cyp (dibenzocycloheptadiene): 2f (thioxanthene), 2g (xanthene), 2h
      (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b
      (phenylmethyl). Their activities at the rat cerebral cortex 5-HT2A receptor were
      (pKi +/- S.E.M.): 8.80 +/- 0.11 (Cyp), 8.60 +/- 0.07 (2f), 8.40 +/- 0.02 (2g),
      8.05 +/- 0.03 (2h), 7.87 +/- 0.12 (2j), 6.70 +/- 0.02 (2i) and 6.45 +/- 0.02
      (3b); those at the rat stomach fundus 5-HT2B receptor (pA2 +/- S.E.M.) were: 9.14
      +/- 0.25 (Cyp), 8.49 +/- 0.07 (2f), 7.58 +/- 0.58 (2g), 7.02 +/- 0.14 (2h), 6.07
      +/- 0.20 (2j), and undetectable (2i, 3b): and those at the pig choroidal plexus 5
      HT2C receptor (pKi +/- S.E.M.) were: 8.71 +/- 0.08 (Cyp), 8.68 +/- 0.01 (2f),
      8.58 +/- 0.20 (2g), 7.95 +/- 0.05 (2h), 7.57 +/- 0.04 (2j), 6.98 +/- 0.04 (2i)
      and 6.63 +/- 0.20 (3b). The slopes did not differ significantly from unity. The
      compounds exhibited the same order of activities at every type of receptor, and
      the most active molecules presented certain steric (butterfly conformation of the
      tricyclic system) and electrostatic (proton affinity on the top of the central
      rings) patterns. It is concluded that the activity of cyproheptadine derivatives
      at 5-HT2 receptors is related to these molecular features, which make feasible a
      common disposition to interact with all three 5-HT2 subtypes.

PMID- 9178522
TI  - Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene
      D4 of [4-[1-(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives.
AB  - In order to find new antiasthmatic agents with dual antagonistic activity against
      thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors, synthesis and
      pharmacological evaluation of various [4-[1-(benzenesulfonamido)
      alkyl]phenyl]alkanoic acid derivatives were undertaken. TXA2 and LTD4
      antagonistic activities in vitro were evaluated by measuring the inhibitory
      effects on L-46619-induced contraction of guinea-pig trachea and LTD4-induced
      contraction of guinea-pig ileum and trachea. Several compounds showed
      satisfactory dual antagonistic activities, and their effect (after oral
      administration) on LTD4-induced bronchoconstriction in guinea-pig in vivo was
      examined. The results demonstrated that both 4-[4-[1-(4
      chlorobenzenesulfonamido)hexyl]phenyl]butyric acid (12e) and 4-[4-[1-(4
      chlorobenzenesulfonamido)-5-methylhexyl]phenyl]bu tyric acid (12m) possessed good
      anti-LTD4 activities. Compounds 12e and 12m were then evaluated for other related
      pharmacological effects involving the arachidonic acid cascade. These compounds
      appear to be hybrid eicosanoids antagonists having antagonistic activity against
      contraction of guinea-pig trachea induced by prostaglandin D2 (PGD2) and PGF2
      sigma, as well as TXA2 and LTD4 antagonistic activities.

PMID- 9178523
TI  - Medicinal foodstuffs. VI. 1) Histamine release inhibitors from kidney bean, the
      seeds of Phaseolus vulgaris L.: chemical structures of sandosaponins A and B.
AB  - Two new olean-12-ene-type triterpene oligoglycosides, named sandosaponins A and
      B, were isolated from kidney bean, the seed of Phaseolus vulgaris L., together
      with three known saponins, soyasaponins I and V and dehydrosoyasaponin 1. The
      structures of sandosaponins A and B were determined on the basis of chemical and
      physicochemical evidence, which included the chemical derivation of
      sandosapogenol from a known sapogenol, soyasapogenol B. Five saponins obtained
      from kidney bean were found to inhibit histamine release from rat exudate cells
      induced by an antigen-antibody reaction and, among them, sandosaponins A and B
      showed the most potent inhibitory activity.

PMID- 9178525
TI  - The development of a cascade impactor simulator based on adhesion force
      measurements to aid the development of dry powder inhalations.
AB  - Adhesion and friction forces are the main physical factors determining the re
      suspension of a micronized drug from carrier particles during inhalation. Hence,
      it appears useful to link adhesion and friction force measurements to the in
      vitro testing of dry powder inhalations, namely the assessment of the mass median
      aerodynamic diameter (MMAD) using an eight-stage Andersen cascade impactor.
      Interactive mixtures of micronized Salmeterol Xinafoate adhered to irrespirable
      lactose monohydrate carrier particles were used as model dosage forms. The
      adhesion force between the drug and carrier particles was assessed using a
      centrifuge technique, and the MMAD was determined under standardized working
      conditions using the Andersen-Cascade impactor (Mark II). A cascade impactor
      simulator (CIS), which is a computer program containing a re-suspension model to
      assess the amount of drug detached from the carrier particles during inhalation,
      was developed and validated using the experimental data. It could be shown, that
      the CIS provided a good estimate of the loss of drug due to adhesion to the
      carrier particles and the loss of drug on the cascade impactor walls. Small
      deviations between the theoretical and experimental mass median aerodynamic
      particle diameters however were found. These deviations were shown to be mainly
      due to the experimental error introduced by the cascade impactor, and that the
      error due to the experimental adhesion measurements is negligibly small. Hence,
      the CIS developed could be a useful tool in early development stages of dry
      powder inhalations to predict the in vitro aerodynamic performance of drug
      particles.

PMID- 9178524
TI  - Biotransformation of (-)-epicatechin 3-O-gallate by human intestinal bacteria.
AB  - The biotransformation of (-)-epicatechin 3-O-gallate (1) and related compounds
      was undertaken using a human fecal suspension. Of fifteen metabolites isolated,
      four compounds were new, namely, two epimers of 1-(3'-hydroxyphenyl)-3-(2",4".6"
      trihydroxyphenyl)propan-2-ols (6, 19); 2",3"-dihydroxyphenoxyl 3-(3',4'
      dihydroxyphenyl)propionate (14) and 1-(3',4'-dihydroxyphenyl)-3-(2",4",6"
      trihydroxyphenyl)propan-2-ol (18). (-)-Epicatechin (2), (-)-epigallocatechin (16)
      and their 3-O-gallates (1, 17) were extensively metabolized by a human fecal
      suspension after incubation for 24 h, whereas the gallates (1, 17) resisted any
      degradation by a rat fecal suspension, even after a prolonged incubation time (48
      h), suggesting a difference in metabolic ability between two intestinal bacterial
      mixtures from different species.

PMID- 9178526
TI  - Synthesis of spin labels for ESR imaging of living rat head.
AB  - Spin labels (7, 10, 13, 16, 22, 27) were synthesized from piperidinyloxyl (1),
      pyrrolidinyloxyl (2), and oxazolidinyloxyl (3). These compounds were injected
      into the carotid artery of anesthetized rats, and the ESR spectra of the rat
      brain were immediately recorded by the use of an L-band ESR spectrometer. Based
      on the spectra obtained, we considered whether or not these spin labels can pass
      the blood brain barrier and bind to brain tissue components.

PMID- 9178527
TI  - Inclusion of trithia[5]heterohelicene by various serum albumins. An effective
      probe for chiral discrimination.
AB  - Racemic 2-hydroxymethyltrithia[5]heterohelicene (2-HT), which has a labile
      helical structure was incorporated into serum albumins of nine species in 1%
      ethanolic aqueous solution, giving 1:1 complexes which exhibited induced circular
      dichroism spectra with species specificity. The application of 2-HT to bovine
      serum as a probe for chiral recognition revealed that the serum itself manifested
      an apparent chiral discrimination between enantiomers of 2-HT.

PMID- 9178528
TI  - Synthesis and biological evaluation of 7-hydroxy-3,4-diphenyl-1,2
      dihydroisoquinolines as new 4-hydroxytamoxifen analogues.
AB  - A phenolic 3,4-diphenyl-1,2-dihydroisoquinoline derivative (4a) as a new 4
      hydroxytamoxifen analogue and a related compound (4c) were synthesized from 3,4
      diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (5a, c), which were prepared by
      intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti
      proliferative activities of 4a,c and 5a,c, as well as 4b and 5b prepared
      previously, against human mammary carcinoma MCF-7 cell line and human
      nasopharyngeal carcinoma KB cell line were evaluated. The 3,4-diphenyl-1,2
      dihydroisoquinoline derivatives (4a,c) and isoquinolin-4-ols (5a,b) were active
      against MCF-7 cells and were nearly equipotent to the corresponding nonphenolic
      compound (1a). The mechanism of the anti-proliferative activity of 4a-c against
      MCF-7 cells is discussed.

PMID- 9178529
TI  - Garsubellin A, a novel polyprenylated phloroglucin derivative, increasing choline
      acetyltransferase (ChAT) activity in postnatal rat septal neuron cultures.
AB  - Garsubellin A (1), a novel polyprenylated phloroglucin derivative, has been
      isolated from the wood of Garcinia subelliptica and its structure has been
      elucidated by spectroscopic analyses. Compound 1 could increase the ChAT activity
      at 10 microM in P10 rat septal neuron cultures.

PMID- 9178530
TI  - Ultrastructural localization of acid phosphatase in some bacteria, after
      treatment with Lubrol W1.
AB  - The ultracytochemical localization of acid phosphatase from some bacteria
      (Listeria monocytogenes, Salmonella typhimurium, Pseudomonas pseudomallei and
      Pseudomonas aeruginosa) was dependent on the changes in the lipoprotein content
      of the membranes as a result of the action of the Lubrol W1.

PMID- 9178531
TI  - Drug resistance in Detroit River gram-negative bacilli.
AB  - Detroit River Gram-negative bacilli were examined for resistance to agents of
      interest to public health. The total recoverable population and the lactose
      fermenting organisms existed at approximately 10(5) and 10(2) colony forming
      units per litre, respectively. Lactose-nonfermenting and lactose-fermenting
      isolates demonstrated resistance to six and four of nine antimicrobial agents,
      respectively, when tested by a paper disc procedure. Multiple resistance in
      lactose-nonfermenting organisms included up to five agents. Lactose-fermenting
      isolates produced multiple resistance to two antibiotics. Only 7% of antibiotic
      resistance strains were proven to contain plasmids. Biochemical testing indicated
      that the most common group of resistant bacteria was Pseudomonas fluorescens.
      Comparison of protein profiles produced by polyacrylamide gel electrophoresis
      indicated that there was variation between P. fluorescens strains demonstrating
      the same multiple resistance.

PMID- 9178532
TI  - Acinetobacter radioresistens metabolizing aromatic compounds. 1. Optimization of
      the operative conditions for phenol degradation.
AB  - A strain of Acinetobacter radioresistens was able to utilize phenol as the only
      carbon and energy source, after an acclimatization period of 3 days in which
      increasing phenol concentrations from 50 to 200 mg/l were supplied. At 30 degrees
      C, the complete phenol utilization in batch degradation tests occurred in 2.5-3 h
      at pH 7 and 8, but it increased strongly at pH 6 (over 40 h). No microbial growth
      was detected at 40 degrees C, while at 20 degrees C (pH 7-8) the time necessary
      for complete phenol degradation was about twofold longer than that at 30 degrees
      C (pH 7-8) revealing a good capability of the strain as a seed-micro-organism for
      enhancing phenol degradation. The bacterial growth in acclimatized cultures,
      evaluated with the viable cell count, always displayed a trend consistent with
      the use of phenol as a substrate with an eventual lag phase and then an
      exponential phase, while in the non-acclimatized cultures an initial stage of
      cellular death was observed.

PMID- 9178533
TI  - A high molecular weight protein from Staphylococcus intermedius cross-reacts with
      Staphylococcus aureus enterotoxin antibodies.
AB  - Enterotoxin production by Staphylococcus species other than Staphylococcus aureus
      has been reported. Staphylococcus strains (104 in toto) representing twelve
      species and subspecies were examined for enterotoxins using a commercial
      staphylococcal enterotoxin ELISA immunoassay (TECRA, International Bioproducts).
      Staphylococcus intermedius (24 strains) and S. aureus (7 strains) were positive
      with this test. Western blots of S. aureus exoproteins demonstrated proteins of
      approximately 30 kD, consistent with known staphylococcal enterotoxins. The major
      antigen in all S. intermedius strains, a 75 kD protein, was not analogous to
      previously described staphylococcal enterotoxins. This protein was unique to S.
      intermedius. Gel filtration data indicate that the protein is a subunit of a
      larger protein in vivo. The 75 kD protein cross-reacts with several enterotoxin
      antibodies. It is unclear whether the protein is a toxin, but its homology with
      S. aureus enterotoxins may indicate a shared toxic region, or this protein may
      create false positive results in screening for enterotoxin.

PMID- 9178534
TI  - Pre-existence and emergence of drug resistance in HIV-1 infection.
AB  - Antiviral treatment of HIV-1 infection often fails because of the rapid emergence
      of resistant virus within weeks of the start of therapy. This raises the question
      of whether resistant viruses pre-exist in drug-naive patients or whether it is
      produced after the start of therapy. Here we compare the likelihood of pre
      existence with the likelihood of production of resistant virus during therapy. We
      show that provided resistant virus pre-exists, then a stronger therapy may lead
      to a greater initial reduction of virus load, but will also cause a faster rise
      of resistant virus. In this case the total benefit of treatment is independent of
      the degree of inhibition of sensitive virus. If, on the other hand, resistant
      mutants do not pre-exist, then the emergence of resistance during treatment
      depends on the efficacy of the drug. If the drug is sufficiently potent to
      eradicate sensitive virus, then the probability that resistant mutants first
      appear during therapy is smaller than the probability that they existed before
      therapy. If the drug cannot eradicate the sensitive virus, then after
      sufficiently long time resistant mutants will appear. However, mutants that are
      unlikely to pre-exist may taken long time to appear.

PMID- 9178535
TI  - Mirror agnosia.
AB  - Normal people rarely confuse the mirror image of an object with a real object so
      long as they realize they are looking into a mirror. We report a new neurological
      sign, 'mirror agnosia', following right parietal lesions in which this ability is
      severely compromised. We studied four right hemisphere stroke patients who had
      left visual field 'neglect'. i.e. they were indifferent to objects in their left
      visual field even though they were not blind. We then placed a vertical
      parasagittal mirror on each patients' right so that they could clearly see the
      reflection of objects placed in the (neglected) visual field. When shown a candy
      or pen on their left, the patients kept banging their hand into the mirror or
      groped behind it attempting to grab the reflection; they did not reach for the
      real object on the left, even though they were mentally quite lucid and knew they
      were looking into a mirror. Remarkably, all four patients kept complaining that
      the object was 'in the mirror', 'outside my reach' or 'behind the mirror'. Thus,
      even the patients' ability to make simple logical inferences about mirrors has
      been selectively warped to accommodate the strange new sensory world that they
      now inhabit. The finding may have implications for understanding how the brain
      creates representations of mirror reflections.

PMID- 9178536
TI  - Influences on the global structure of cortical maps.
AB  - Cortical maps often contain global spatial structure: however, theoretical
      accounts for their development have generally concentrated on reproducing only
      local structure. We show that the elastic net model of cortical map formation can
      closely approximate the global structure of the ocular dominance column map
      observed in macaque primary visual cortex. A key component is the assumption of
      spatially non-uniform and anisotropic correlations in the retina. This work shows
      how genetic and epigenetic effects could combine to establish characteristic
      global structure in cortical maps.

PMID- 9178537
TI  - Promotion of regeneration and axon growth following injury in an invertebrate
      nervous system by the use of three-dimensional collagen gels.
AB  - We describe the application of three-dimensional collagen matrices to the study
      of nerve cord repair in the leech. Our experiments show that ganglia and
      connectives of the leech ventral nerve cord can be maintained for up to four
      weeks embedded in 3D gels constructed from mammalian type I collagen. Severed
      nerve cords embedded in the collagen gel reliably repaired within a few days of
      culture. The gel was penetrable by cells emigrating from the cut ends of nerves
      and connectives, and we consistently saw regenerative outgrowth of severed
      peripheral and central axons into the gel matrix. Thus, 3D gels provide an in
      vitro system in which we can reliably obtain repair of severed nerve cords in the
      dish, and visualize cell behaviour underlying regenerative growth at the damage
      site: and which offers the possibility of manipulating the regenerating cells and
      their extracellular environment in various ways at stages during repair. Using
      this system it should be possible to test the effect on the repair process of
      altering expression of selected genes in identified nerve cells.

PMID- 9178538
TI  - Implications of recent geological investigations of the Mozambique Channel for
      the mammalian colonization of Madagascar.
AB  - Madagascar separated from continental Africa during the break-up of Gondwanaland
      early in the Cretaceous. The presence of several terrestrial mammalian groups on
      Madagascar is paradoxical as (i) these groups postdate the departure of
      Madagascar from Africa: and ii) terrestrial mammals are poor dispersers across
      wide water barriers. Recent geological studies focusing on the Davie Fracture
      Zone of the Mozambique Channel offer a resolution to this situation, by
      suggesting the presence of a land-bridge from the mid-Eocene to the early
      Miocene, an interval that matches the ages of Madagascar's mammalian groups.

PMID- 9178539
TI  - Localization of S1- and S2-like immunoreactivity in the nervous system of the
      brittle star Amphipholis squamata (Delle Chiaje 1828).
AB  - The recent isolation and characterization of the SALMFanide neuropeptides S1
      GFNSALMFamide; and S2 (SGPYSFNSGLTFamide) from the sea stars. Asterias rubens and
      Asterias forbesi have initiated numerous studies on their morphological
      localization and distribution within the phylum Echinodermata. It has been shown
      by immunocytochemistry and radioimmunoassay that these peptides are widely
      distributed in the nervous system of some asteroids, echinoids and ophiuroids. A
      physiological approach has also shown that S1 and S2 potentiate the luminescence
      of the small ophiuroid Amphipholis squamata. In the present study. S1- and S2
      like immunoreactivity have been localized in A. squamata by immunocytochemistry
      on both wholemount preparation and histological sections. The results reveal a
      widespread neuronal distribution of S1-like immunoreactivity in the circumoral
      ring, radial nerve cord, and tube feet. S1-like immunoreactivity was found to be
      associated with axons and cell bodies in both the ectoneural and hyponeural
      components of the nervous. S2-like immunoreactivity was detected only in the
      ectoneural plenus of the circumoral ring and radial nerve cord.

PMID- 9178540
TI  - Genetic and behavioural evidence of monogamy in a mammal, Kirk's dik-dik (Madoqua
      kirkii).
AB  - Little is known about the mating behaviour of monogamous mammals. Here, we
      present behavioural and genetic evidence of fidelity in a socially monogamous
      dwarf antelope, Kirk's dik-dik. DNA microsatellite analysis revealed no evidence
      of extra-pair paternity (EPP) in dik-diks: mothers' partners matched the paternal
      genotype in all 12 juveniles tested. One likely reason for the absence of EPP is
      that males guard their mates closely during oestrus and over-mark all female
      scent, thereby reducing the likelihood of other males attempting to mate. In
      addition, males may be limited in their ability to search for extra-pair
      populations (EPCs) by activities associated with pair-bond maintenance. Year
      round, males maintained proximity within pairs, followed their females' activity
      patterns, and spent approximately 64% of their time with their partners. However,
      males did attempt to obtain EPCs when the opportunity arose, and genetic monogamy
      in dik-diks is probably best explained by the behaviour of females: in contrast
      to many monogamous female birds, female dik-diks do not appear to seek EPC
      partners. We propose that females avoid extra-pair males because they are unable
      to mate with them without instigating a potentially dangerous conflict.

PMID- 9178542
TI  - Historical rainforest contractions, localized extinctions and patterns of
      vertebrate endemism in the rainforests of Australia's wet tropics.
AB  - The spatial patterns in the distributions of vertebrates in the rainforests of
      the wet tropics biogeographic region of north-eastern Australia were examined to
      form hypotheses on the processes that have shaped vertebrate assemblages and
      patterns of species richness and regional endemism. These rainforests occur in a
      relatively narrow and discontinuous strip along the coast of north-eastern
      Australia. We found that the number of regionally endemic species and the
      proportion of regional endemics present in each subregion are both strongly
      related to the geographic shape of subregional patches of rainforest, independent
      of rainforest area, within Australian tropical rainforests. Shape has a more
      significant influence on regional endemism than area, and area has a stronger
      influence on species richness. These patterns were congruent for all terrestrial
      vertebrate classes manuals, birds, reptiles and frogst, and for the four groups
      combined. Our results suggest that the combination of current rainforest area and
      shape are an index of the relative susceptibility of each area of rainforest to
      historical contractions, with the implication that historical habitat
      fluctuations, coupled with subsequent localized extinctions species sifting; have
      been extremely important processes in determining current patterns of endemism in
      Australia's wet tropical rainforests. This hypothesis is supported by the highly
      nested structure of the subregional distribution patterns.

PMID- 9178541
TI  - Selection and fitness in bacteriocin-producing bacteria.
AB  - Bacteriocins are proteinaceous anticompetitor molecules produced by bacteria
      against closely related species. A number of theoretical models have been used to
      explain experimental data that indicate high polymorphisms among bacteriocins and
      a frequency-dependent nature of selection for bacteriocin-producing strains. The
      majority of these experimental data were, however, obtained from investigations
      into the colicin group of bacteriocins produced by Gram-negative bacteria. The
      conclusions drawn from these models have been extrapolated to other bacteriocins
      and allelopathic compounds in general. Examination of more recent experimental
      investigations into the bacteriocins of Gram-positive bacteria indicate a lower
      degree of polymorphism and a less frequency dependent mode of selection among
      these strains them among the colicin-producing strains. Here we examine these
      contradictions in the light of the assumptions and conclusions of the theoretical
      models and reported data. We show that fitness costs as indicated by decreased
      relative maximum growth rate associated with bacteriocin production may be much
      lower in many cases than is assumed in the present models. A lower fitness cost
      associated with bacteriocin production adequately explains the newer data from
      Gram-positive bacteria cited here, and indicates that extrapolation of existing
      models to all bacteriocins and other allelopathic compounds is not appropriate.

PMID- 9178543
TI  - Genotypic variation among different phenotypes within aphid clones.
AB  - Most aphid species Hemiptera: Aphididae are parthenogenetic between periods of
      sexual reproduction. They are also highly polyphenic, with different adult morphs
      occurring in the life cycle, piz. winged, wingless, asexual and sexual. It is
      assumed that aphids born in a parthenogenetic clonal lineage are genetically
      identical regardless of the final adult form with the exception of sexual forms).
      Using the randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR)
      we have found that different asexual adult phenotypes winged and wingless of some
      clones of two cereal aphid species (the grain aphid, Sitobion avenae (F.) and the
      bird-cherry aphid. Rhopalosiphum padi (L.) may be distinguished by the presence
      or absence of one or more RAPD-PCR bands. In three of nine clones examined, such
      differences were found, and Southern blotting and hybridization of the
      discriminating bands confirmed these to be of aphid origin, rather than due to
      endosymbiotic bacteria or contaminating fungi. The main 248 and 296 bp bands, in
      the two species respectively, were sequenced and found to be A/T rich. The
      smaller band showed 57% homology with white striated muscle over a stretch of 90
      bp. Genomic DNA treated with dimethyl sulphoxide to remove secondary structures
      still showed differences in RAPD-PCR profiles between winged and wingless morphs
      within the unusual clones. This discovery may be widespread and therefore it is
      important to understand the phenomenon in relation to clonal organisms.

PMID- 9178544
TI  - CSlo encodes calcium-activated potassium channels in the chick's cochlea.
AB  - Large conductance, calcium-activated (BK) potassium channels play a central role
      in the excitability of cochlear hair cells. In mammalian brains, one class of
      these channels, termed Slo, is encoded by homologues of the Drosophila 'slowpoke'
      gene. By homology screening with mouse Sla cDNA, we have isolated a full-length
      clone (cSlo1) from a chick's cochlear cDNA library, rSlol had greater than 90%
      identity with mouse Slo at the amino acid level, and was even better matched to a
      human brain Slo at the amino and carboxy termini. cSlol had none of the
      additional exons found in splice variants from mammalian brain. The reverse
      transcriptase polymerase chain reaction (RT-PCR) was used to show expression of
      cSlal in the microdissected hair cell epithelium basilar papilla. Transient
      transfection of HIEK 293 cells demonstrated that cSlol encoded a potassium
      channel whose conductance averaged 224 pS at +60 mV in symmetrical 140 mM K.
      Macroscopic currents through cSlol channels were blocked by scorpion toxin or
      tetraethyl ammonium, and were voltage and calcium dependent. cSlol is likely to
      encode BK-type calcium-activated potassium channels in cochlear hair cells.

PMID- 9178545
TI  - Molecular evolution of imprinted genes: no evidence for antagonistic coevolution.
AB  - Genomically imprinted genes are those for which expression is dependent on the
      sex of the parent from which they are derived. Numerous theories have been
      proposed for the evolution of genomic imprinting: one theory is that it is an
      intra-individual manifestation of classical parent -offspring conflict. This
      theory is unique in predicting that an arms race may develop between maternally
      and paternally derived genes for the control of foetal growth demands. Such
      antagonistic coevolution may be mediated through changes in the structure of the
      proteins concerned. Comparable coevolution is the most likely explanation for the
      rapid changes seen in antigenic components of parasites and antigen recognition
      components of immune systems. We have examined the evolution of insulin-like
      growth factor Igf2, and its antagonistic receptor Igf2r) and find that in
      contrast to immune genes, at the sites of mutual binding they are highly
      conserved. In addition, we have analysed the rate of molecular evolution of seven
      imprinted genes including Igf2 and Igf2r), sequenced in both mouse and rat, and
      had that this is the same as that of nonimprinted receptors and significantly
      lower than that of immune genes controlling for differences in mutation rates.
      Contrary to the expectations of the conflict hypothesis, we hence find no
      evidence for antagonistic coevolution of imprinted genes mediated by changes in
      sequence.

PMID- 9178547
TI  - An adaptationist view of apoptosis.
AB  - A cell's decision whether to undergo apoptosis (cell suicide) is examined here
      from an adaptationist perspective, rather than a mechanistic one. External and
      internal inputs to the cell's protein-based information processing network are
      used in making this decision, with the cell factoring in its replaceability. A
      system in which each cell takes primary responsibility for deciding its own fate
      has great adaptive value because it harnesses each cell's self-knowledge rather
      than waiting for external cues to be recognized by other cells. Cell self
      destruction can be an important selective mechanism, potentially leading to
      better performance of tissues over time. However, reliance on cells to monitor
      themselves has a flaw, since cells may incur selfish mutations that impair their
      apoptotic responsibility. The tight control exerted over somatic cells serves to
      check selfish genes involved in neoplasia and viral infections. Germ cells appear
      to be similarly monitored, both by other germ cells and by supporting follicular
      or Sertoli cells, thus maintaining the advantages offered by an apoptotic system.
      The adaptationist approach views the limited replacement of neurons and cardiac
      myocytes as likely to have net survival value. The linkage of these cells into a
      network with their neighbors throughout a lifetime allows for a precisely
      functioning team of cells expected to compensate for gradual declines in
      individual cell functionality. Replacement of apoptotic cells with naive cells
      might decrease brain functionality and might risk upsetting the conduction of
      cardiac impulses. The evolutionary viewpoint lends itself to new hypotheses, but
      only the boldest speculator would have predicted a system in which cells are
      given primary responsibility for deciding whether to kill themselves when they
      deem it beneficial to the organism.

PMID- 9178546
TI  - Neural responses to salient visual stimuli.
AB  - The neural mechanisms involved in the selective processing of salient or
      behaviourally important stimuli are uncertain. We used an aversive conditioning
      paradigm in human volunteer subjects to manipulate the salience of visual stimuli
      (emotionally expressive faces) presented during positron emission tomography
      (PET) neuroimaging. Increases in salience, and conflicts between the innate and
      acquired value of the stimuli, produced augmented activation of the pulvinar
      nucleus of the right thalamus. Furthermore, this pulvinar activity correlated
      positively with responses in structures hypothesized to mediate value in the
      brain right amygdala and basal forebrain (including the cholinergic nucleus
      basalis of Meynert). The results provide evidence that the pulvinar nucleus of
      the thalamus plays a crucial modulatory role in selective visual processing, and
      that changes in perceptual salience are mediated by value-dependent plasticity in
      pulvinar responses.

PMID- 9178548
TI  - Studies on biosynthesis of brassinosteroids.
AB  - Biosynthesis of steroidal plant hormones, brassinosteroids, was studied using the
      cell culture system of Catharanthus roseus. Feeding labeled compounds of possible
      intermediates to the cultured cells, followed by analyzing the metabolites by gas
      chromatography-mass spectrometry disclosed the pathways from a plant sterol,
      campesterol, to brassinolide. There are two pathways, named the early C6
      oxidation pathway and late C6-oxidation pathway, both of which would be operating
      in a wide variety of plants. Recent findings of brassinosteroid-deficient mutants
      of Arabidopsis and the garden pea by several groups, and the possible blocked
      steps of the mutants in the biosynthetic pathways are also introduced.

PMID- 9178549
TI  - Effect of dietary n-3/n-6 fatty acid ratio on the total count, fatty acid
      composition, and histamine and leukotriene concentrations of mast cells in tunica
      mucosa bronchiorum of type I allergic guinea pig.
AB  - To search for the most effective dietary n-3/n-6 ratio to suppress the type I
      allergic response, we performed basic experiments that applied parameters,
      associated with the type I allergy. Guinea pigs fed on diets containing lipids
      with the n-3/n-6 ratio at different levels and the polyunsaturated fatty
      acid/saturated fatty acid ratio of a fixed level were sensitized with ovalbumin
      and reared for two weeks. The lowest or critical level of the n-3/n-6 ratio which
      produced a significant difference in the parameters was as follows: about 2.0 for
      the response of mast cells and eosinophils; 0.5 and 1.0, respectively, for the
      uptake of n-3 and n-6 polyunsaturated fatty acids and decreased histamine
      production; and 0.2 for decreased leukotriene B4 and total leukotrienes 4, and
      increased leukotrienes 5/leukotrienes 4. The critical level of the n-3/n-6 ratio
      thus differed widely according to the parameter. Overall, the upper limit for the
      dietary n-3/n-6 ratio to suppress antigen-induced type I allergic responses is
      suggested to be around 1.0.

PMID- 9178550
TI  - Oxygen sensitivity of NifA protein of Azospirillum lipoferum FS as suggested by
      gene cloning and expression in Escherichia coli.
AB  - We cloned and sequenced a 2.8-kb SalI fragment of Azospirillum lipoferum FS as a
      homologue of the Klebsiella oxytoca nifA gene. The amino acid sequence deduced
      from an open reading frame of 1872 bases showed 91% identity to that of the A.
      brasilense NifA, and the putative central sigma54 interaction domain was
      conserved as well as the C-terminal DNA-binding domain. The NifA function on the
      nifH promoter was examined in Escherichia coli using a combination of a nifA
      driver plasmid and a nifH-lacZ reporter plasmid, in which the transcriptional
      activation of the nifH promoter by the NifA was evaluated with the beta
      galactosidase activity. The A. lipoferum NifA activated the nifH promoter solely
      under microaerobic conditions, while the K. oxytoca NifA activated it
      irrespective of the oxygen condition. These observations suggest that oxygen
      sensitivity is an intrinsic property of the A. lipoferum NifA.

PMID- 9178551
TI  - In vitro and in vivo anti-platelet effects of enzymatic hydrolysates of collagen
      and collagen-related peptides.
AB  - Collagen-related peptides, Gly-Pro-Arg and its analogues, were examined for their
      inhibitory effects on platelet aggregation induced by the addition of ADP. Human
      platelet aggregation was suppressed by more than 50% with each of Gly-Pro-Arg and
      such Gly-Pro-Arg-containing peptides as Gly-Pro-Arg-Gly, Gly-Pro-Arg-Gly-Pro, Gly
      Pro-Arg-Pro-Pro, and Gly-Pro-Arg-Pro-Pro-Pro at a concentration of 0.3 mM. The
      inhibitory effects of these peptides were about 10 times higher in human PRP than
      in rat PRP. Other Gly-Pro-Arg analogues such as Sar-Pro-Arg, Gly-Pro-Lys, Gly-Ala
      Arg, and Ala-Gly-Pro-Arg had no inhibitory effect at a concentration from 0.1 to
      0.8 mM even in human PRP. Intravenous and oral administrations of Gly-Pro-Arg and
      enzymatic hydrolysates of collagen suppressed the decrease in platelet count for
      endotoxin-induced DIC in rats. Collagen itself has been regarded as a potent
      inducer of platelet aggregation, but these findings suggest that collagen-related
      peptides and enzymatic hydrolysates of collagen prevent platelet aggregation.

PMID- 9178552
TI  - Growth inhibition, morphological change, and ectoenzyme release of LLC-PK1 cells
      by phosphatidylinositol-specific phospholipase C of Bacillus thuringiensis.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus
      thuringiensis added to a culture of LLC-PK1 cells inhibited cell growth by 40%.
      In contrast with normal cells, the cells cultured in the presence of PI-PLC
      showed needle-like appendages which seemed to have been formed due to portions of
      the cell remaining adhered to the culture dish as the cell shrank. When LLC-PK1
      cells were treated with PI-PLC, significant amounts of alkaline phosphatase and
      alkaline phosphodiesterase I were released specifically from the apical surface
      of the LLC-PK1 cells. Furthermore, PI-PLC treatment caused a delay of enzyme
      production and dome formation. These data indicate that glycosyl
      phosphatidylinositol (GPI)-anchored proteins on the surface of LLC-PK1 cells are
      important in cell growth and differentiation. Also, the combined use of LLC-PK1
      cells and PI-PLC of B. thuringiensis is effective for investigating the function
      of GPI-anchor proteins.

PMID- 9178553
TI  - Characterization of the protein and glycan moieties in different forms of bovine
      lactoferrin.
AB  - The BrCN cleavage of lactoferrin-a or -b (LF-a or LF-b) led to the observation of
      four fragments by SDS-PAGE, whose molecular masses were 77, 58, 52, and 30 kDas,
      or 74, 54, 47, and 30 kDas, respectively. N-Terminal amino acid sequence analyses
      show that the sequences of 58, 52, and 30 kDa fragments (residues 64-471, 130
      471, and 472-689) of LF-a coincide with those of the 54, 47, and 30 kDa fragments
      of LF-b. respectively. All these fragments, which were positive by PAS staining,
      were not stained after being treated with glycopeptidase F. This treatment
      changed the 58 and 52 kDa fragments of LF-a to the 54 and 47 kDa fragments,
      respectively, whose molecular masses were the same as those of the treated
      fragments of LF-b. The 58 and 52 kDa fragments of LF-a bound to the lectin,
      Ricinus communis agglutinin, while the 54 and 47 kDa fragments of LF-b hardly
      bound to it.

PMID- 9178554
TI  - Thermal gelation profile changes in reconstituted actomyosin due to storage under
      a high salt concentration and low temperature.
AB  - Changes in the heat-induced gelation properties of reconstituted rabbit skeletal
      actomyosin stored under a high salt concentration at pH 6.0 and 0 degree C were
      investigated at different weight ratios of actin to myosin by using dynamic
      rheological and biochemical measurements. The addition of actin resulted in a
      pronounced peak maximum at about 50 degrees C and an accompanying temporary
      reduction in the range at about 50 degrees C to 60 degrees C. The more the
      initial actin concentration was increased, the greater was the area of the
      peak/shoulder. However, this area was markedly diminished with increasing storage
      time. As a result, the dynamic rheological pattern was transformed from an
      actomyosin type into a myosin type. The relationship between the G' value at 80
      degrees C and the actin/myosin weight ratio was curvilinear, with a peak at the
      ratio of 0.05, immediately after storage was started. This profile changed during
      storage, depending on the extent to denaturation of actin and myosin in the
      reconstituted actomyosin (RAM). The G' value of actomyosin in 0.5 M KCl with a
      small actin/myosin ratio of 0.05 decreased to one-half of its initial value after
      7 days of storage, whereas the G' value with a large actin/myosin ratio of 0.225
      increased by about 1.6 times. In 1.5 M KCl, all the G' values declined to the
      level with myosin alone after 7 days of storage. The time-course plots of the
      remaining actin concentration in RAM at different weight ratios of actin to
      myosin after being treated with 0.5 M or 1.5 M KCl showed a decrease in the actin
      content with increasing storage time, and an increase in the KCl concentration to
      1.5 M KCl promoted the denaturation of actin in RAM faster than with 0.5 M KCl.
      The surface hydrophobicity of each RAM sample progressively increased with
      increasing storage time, while little significant increase in the sulfhydryl (SH)
      content during storage was observed. It is concluded that changes in the heat
      induced gelation properties of actomyosin during storage are largely attributable
      to the denaturation of actin rather than to the denaturation of myosin or to
      quantitative changes in the SH content and hydrophobicity.

PMID- 9178556
TI  - Efficient expression of mono- and diacylglycerol lipase gene from Penicillium
      camembertii U-150 in Aspergillus oryzae under the control of its own promoter.
AB  - The gene, mdlA, coding for mono- and diacylglycerol lipase from Penicillium
      camembertii U-150 was expressed efficiently in Aspergillus oryzae under the
      control of its own promoter. The gene product was secreted into the culture
      medium with a highest productivity of 1 g/liter and correctly processed at both N
      and C-termini. KEX2-like processing was suggested to occur at the C-terminus in
      both A. oryzae and P. camembertii. Specific activity and substrate specificity of
      the purified recombinant protein were also almost the same to that of native
      protein but the extent of N-glycosylation in the recombinant protein was about
      half of that of the native protein. The presence of introns did not seem to
      affect the gene expression. The mdlA expression was induced by lipids and
      regulated transcriptionally in A. oryzae as well as P. camembertii. Promoter
      deletion analysis showed that the region between the positions at -382 and -554
      bp from the translation initiation point was important to the higher expression
      of mdlA. The promoter sequence of mdlA was compared to that of the Geotrichum
      candidum lipase gene, which is also reported to be inducible by lipids, with
      three commonly observed oligonucleotide sequences.

PMID- 9178555
TI  - Characterization of 30-kDa fragments derived from beta-conglycinin degradation
      process during germination and seedling growth of soybean.
AB  - The degradation process of beta-conglycinin, a vicilin-type glycosylated storage
      protein of soybean seeds, during germination and seedling growth was examined by
      concanavalin A blotting combined with polyacrylamide gel electrophoresis. We
      detected and analyzed the structures of key intermediary fragments of 30 kDa
      derived from beta-conglycinin degradation, they were proved to be single-domain
      type subunits of beta-conglycinin. We show here a degradation process of beta
      conglycinin: beta-conglycinin is subjected to limited proteolysis at exposed
      regions on the molecular surface, like domain junctions, generating 30-kDa single
      domain fragments before non-specific proteolysis.

PMID- 9178557
TI  - Purification of amylases and other enzymes by a forced-affinity chromatography
      method.
AB  - An affinity matrix of soluble starch gel was prepared by cross-linking catalyzed
      by epichlorohydrin. The elution pattern of Taka-amylase A (TAA) indicated that
      the amount of enzyme bound to the starch gel column increased with increases in
      the ammonium sulfate (AmS) concentration in the equilibrating buffer. TAA had an
      affinity for the gels with a starch structure, and desorbed from the column with
      the buffer containing no AmS. Bound TAA was also eluted with starch and
      cyclodextrin solution. The AmS stimulative effect was partially replaced by
      polyethylene glycol and surfactants. Besides TAA, various, other amylases bound
      satisfactorily to the starch gel. Moreover, affinity purifications of dextranase,
      cellulase, and pectinase were done by gels with dextran, cellulose, and pectin
      structures, respectively. By the aid of forced effects of AmS, various
      carbohydrases could be purified by the affinity gels of polysaccharide linked by
      epichlorohydrin.

PMID- 9178558
TI  - Lipid peroxidation in linoleic acid micelles caused by H2O2 in the presence of
      myoglobin.
AB  - We investigated the lipid peroxidation in linoleic acid micells caused by H2O2 in
      the presence of metmyoglobin by monitoring the oxygen consumption. O2 consumption
      usually consisted of two phases. In the first phase, it occurred slowly and
      linearly until the concentration of linoleic acid hydroperoxide reached a certain
      value, rapid consumption, presumably by a chain reaction, then followed in the
      second phase. No effects of diethylenetriaminepentaacetic acid (DTPA) on the
      induction period (the period during the first phase) and the maximum oxygen
      consumption rate (MOCR) in the second phase indicate that free ferric ions
      liberated from myoglobin had no role in any phases during the lipid peroxidation.
      The differing dose effects of ascorbic acid, alpha-tocopherol, and sodium nitrite
      on the induction period and MOCR reflect their respective antioxidative
      mechanisms during lipid peroxidation.

PMID- 9178559
TI  - High-level expression of the chemically synthesized gene for microbial
      transglutaminase from Streptoverticillium in Escherichia coli.
AB  - We developed a novel approach for the high-level production of a microbial
      transglutaminase (TGase) from Streptoverticillium in E. coli. The direct
      expression of the TGase gene in E. coli cells did not cause overproduction,
      probably due to the harmful influence of TGase activity, which introduces
      covalent crosslinks between proteins. Therefore, we fused the chemically
      synthesized TGase gene coding for the entire 331 amino acid residues at the amino
      terminus to a bacteriophage T7 gene 10 leader peptide (260 amino acids) using an
      inducible expression vector. The TGase gene was expressed as inclusion bodies in
      the E. coli cytoplasm. Restoring 15 amino acid residues upstream of the amino
      terminus of the mature TGase by a two-step deletion of the fusion sequence
      facilitated solubilization and subsequent proteolytic cleavage, thus releasing
      mature TGase. Although the mature form had less TGase activity than native TGase,
      because of the poor refolding rate, these results suggest that this system is
      suitable for the efficient production of TGase.

PMID- 9178560
TI  - Effects of dietary sesaminol and sesamin on eicosanoid production and
      immunoglobulin level in rats given ethanol.
AB  - The effects of sesaminol and sesamin on the ethanol-induced modulation of immune
      indices related to food allergy were examined in rats given a low (10%)-casein
      diet. Chronic ethanol drinking, at the dietary level of 23% (w/w), significantly
      increased the plasma IgA and IgM concentrations, irrespective of the presence of
      0.1% and 0.2% sesaminol, but the effects disappeared with 0.2% sesamin. A
      significant IgG-elevating effect of these lignans was also found. In contrast,
      the concentration of plasma IgE was not influenced by the dietary manipulation.
      Although ethanol drinking did not influence splenic leukotriene B4 production,
      sesaminol tended to decrease it dose dependently, while sesamin increased the
      plasma prostaglandin E2 concentration. These results suggest that sesaminol and
      sesamin seems to have a diverse effect on the plasma levels of immunoglobulins
      and eicosanoids.

PMID- 9178561
TI  - High level expression of XMP aminase in Escherichia coli and its application for
      the industrial production of 5'-guanylic acid.
AB  - To improve the efficiency of the enzymatic conversion of 5'-xanthylic acid (XMP)
      to 5'-guanylic acid (GMP), we attempted to increase the activity of the
      conversion enzyme, XMP aminase (GMP synthetase) encoded by the guaA gene in
      Escherichia coli. By connecting the PL promoter of lambda phage, the SD sequence
      of trpL of E. coli, and ATG, at a suitable position upstream of the guaA gene, we
      obtained plasmid pPLA66. Sequencing of the nucleotides of the upstream region of
      the guaA gene on pPLA66 showed that the C-terminal region of the guaB gene, which
      encodes IMP dehydrogenase, was conserved and a short peptide consisted of 14
      amino acids was coded. E. coli MP347/pPLA66 showed an increase in the activity of
      approximately 370 times when compared with that of the strain MM294, and the
      amount of the enzyme protein represented approx. 34% of the total cellular
      protein. Strain MP347/pPLA66 was cultivated in a 5-liter jar fermentor using a
      medium which contained mainly corn steep liquor. The culture broth had high XMP
      aminase activity. In the conversion reaction using mixed broths consisted of 600
      ml of XMP-fermentation broth of Corynebacterium ummoniagenes KY13203 and 30 ml of
      cultured broth of E. coli MP347/pPLA66, a surfactant, Nymeen S-215 and xylene
      were added to the reaction mixture to make the cell membrane permeable to
      nucleotides. After 23 h of the reaction, 70 mg/ml (131 mM) of GMP.Na2.7H2O was
      accumulated from 83 mg/ml (155 mM) of XMP.Na3.7H2O, without addition of ATP. The
      molar conversion yield was approx. 85%. The facts that the cell membrane was
      treated to allow nucleotides to permeate and that the conversion reaction
      proceeded well enough in spite of a small amount of E. coli cells indicate ATP
      was regenerated from AMP by C. ammoniagenes cells and supplied to E. coli cells.
      Therefore, it was considered that the coupling reaction between these two kind of
      strains was established.

PMID- 9178562
TI  - Sequential binding of Staphylococcal gamma-hemolysin to human erythrocytes and
      complex formation of the hemolysin on the cell surface.
AB  - Staphylococcal gamma-hemolysin consists of two protein components, F (or H gamma
      I) and H gamma II. To elucidate the mode of action of gamma-hemolysin, we studied
      the binding order of F and H gamma II to human erythrocytes and the cell-bound
      state of the two components. The binding of F to human erythrocytes preceded the
      binding of H gamma II to the cells, and thereafter hemolysis occurred. Western
      immunoblot analysis of the cell-bound gamma-hemolysin indicated that F and H
      gamma II components form high-molecular-mass (150-250 kDa) complexes on the
      erythrocytes. The toxin complexes were recovered in a Triton X-100-insoluble
      fraction of the erythrocytes, which contains cytoskeleton proteins. Neither the
      formation of the toxin complex(es) nor hemolysis occurred when the erythrocytes
      were treated with proteinase K. Abortion of the complex formation on the
      proteinase K-treated erythrocytes may be due to the failure of the binding of H
      gamma II to the cells, because F bound to the proteinase K-treated erythrocytes
      to the same extent as to the non-treated erythrocytes.

PMID- 9178563
TI  - Purification and characterization of a dipeptidyl carboxypeptidase from
      Pseudomonas sp. WO24.
AB  - A dipeptidyl carboxypeptidase (DCP) activity was detected in cell-free extracts
      of Pseudomonas sp. WO24. After purification and characterization the enzyme was
      found to be homogeneous by SDS-PAGE, and had a molecular mass of 74,000 Da by SDS
      PAGE and 72,000 Da by gel filtration, indicating that it is monomeric. The
      isoelectric point was 5.2 and optimum pH was 6.5-7.0. It showed a specific
      activity of 780 mumol/min/mg, which is the highest of the values shown by known
      enzymes. The enzyme hydrolyzed angiotensin I to angiotensin II and sequentially
      released Phe-Arg and Ser-Pro from the C-terminus bradykinin. The DCP could not
      cleave imido-bonds, Gly-Gly bonds, or tripeptides. The enzymatic activity was
      completely inhibited by 0.001 mM EDTA and 0.1 mM O-phenanthroline, but it was not
      affected by general serine and cysteine protease inhibitors. Addition of Zn2+
      completely restored the original activity of the inactivated DCP treated with
      EDTA. These results suggest that this enzyme is a zinc metalloprotease. The
      characteristics of the purified enzyme are slightly different from those of the
      DCPs from Escherichia coli, Pseudomonas maltophilia, and Corynebacterium equi,
      and considerably from those of the DCP from Bacillus pumilus.

PMID- 9178564
TI  - Acyl amino acid derivatives as novel inhibitors of influenza neuraminidase.
AB  - We searched our chemical collection to identify non-N-acetylneuraminate (NeuAC)
      inhibitors of influenza neuraminidase (NA). Of the 62 acyl derivatives tested,
      several acyl amino acids, but not acyl alkanolamine derivatives, were effective
      and inhibited the NA activity in a dose-dependent manner. N-3-Hydroxymyristoyl D
      cysteine and N-myristoyl-O-caproyl-D-serine were the more potent compounds and
      inhibited the enzyme in a noncompetitive manner (Ki = 102 and 125 microM,
      respectively) without respect to the substrate. An important consideration for
      the choice of inhibitor is the selectivity of the inhibition. These compounds
      were selective inhibitors of viral NA and effective for any variant enzyme, but
      the enzymes from V. cholerae and human placenta were insensitive. Accordingly,
      the acyl amino acid derivatives may be expected to be inhibitors without cellular
      toxicity and may serve as lead compounds for anti-influenza agents.

PMID- 9178565
TI  - Cloning and sequencing of a cDNA encoding alpha-glucosidase from sugar beet.
AB  - A cDNA encoding sugar beet alpha-glucosidase was cloned from a library
      constructed from mRNA of suspension-cultured cells. The cDNA, 3056 bp in length,
      had an open reading frame encoding a polypeptide of 913 amino acid residues with
      a molecular mass of 102,078 Da, included only one of four regions which were
      conserved in the alpha-amylase family of enzymes. The deduced amino acid sequence
      from the analysis of the cDNA contained the sequences of the proteolysis peptides
      and the active site region peptide of sugar beet alpha-glucosidase. The primary
      structure indicated relatively high homology in the range of 28.2 to 54.3% to
      those for other alpha-glucosidases. The highest homology was found in barley
      alpha-glucosidase.

PMID- 9178566
TI  - Isolation and partial amino acid sequence of bacteriocins produced by
      Lactobacillus acidophilus.
AB  - Bacteriocins produced by Lactobacillus acidophilus JCM 1023, JCM 1028, JCM 1021,
      JCM 1229, and JCM 5342 were active against closely related lactobacilli. These
      bacteriocins were purified and partial sequenced. Bacteriocin activities of L.
      acidophilus JCM 1023 and JCM 1028 were associated with two components. On the
      basis of N-terminal amino acid sequencing and the molecular masses, it is
      interpreted that these two-component bacteriocins are identical to acidocin
      J1132, a bacteriocin from L. acidophilus JCM 1132 [Tahara et al., Appl. Environ.
      Microbiol., 62, 892-897 (1996)]. Other bacteriocins were single-peptide
      bacteriocins.

PMID- 9178567
TI  - Stimulating effect of ileal pancreaticobiliary secretion on ileal apolipoprotein
      A-IV mRNA expression in fasted rats.
AB  - The effect of pancreaticobiliary secretion on the intestinal expression of the
      apo A-IV gene was examined in fasted rats. Pancreaticobiliary diversion, but not
      biliary diversion alone, into the ileum increased the ileal apo A-IV mRNA
      expression by 24 h post-operation. Jejunal apo A-IV mRNA was reduced by biliary
      exclusion. The data suggest that the biliary constituent plays an important role
      in the apo A-IV gene expression in the entire length of the small intestine, and
      that up-regulation of the apo A-IV gene requires exocrine pancreatic in addition
      to biliary secretion.

PMID- 9178568
TI  - Biological activity of purpurogallin.
AB  - Purpurogallin showed antibacterial activity toward gram-positive bacteria. Strong
      activity against methicillin-resistant Staphylococcus aureus [minimal inhibitory
      concentration (MIC) against methicillin of 1600 micrograms/ml] was found, with
      MIC of 11.0 micrograms/ml. Purpurogallin inhibited the growth of all tested
      plants and decreased the chlorophyll content in the cotyledons of Brassica
      campestris subsp. rapa. It showed potent inhibitory activity against prolyl
      endopeptidase (the 50% inhibitory concentration was 1.6 x 10(-5) M), unlike its
      analogues, hinokitiol and tropolone.

PMID- 9178569
TI  - Selective incorporation of polyunsaturated fatty acids into organelle
      phospholipids of animal cells.
AB  - The selective incorporation of linoleic (18:2(n-6)) and docosahexaenoic (22:6(n
      3)) acids into phospholipids of mitochondria, endoplasmic reticulum, and plasma
      membrane was investigated by changing the ratio of 22:6(n-3) against 18:2(n-6) in
      a medium, in which Chinese hamster V79-R cells were grown. In those organelles,
      18:2(n-6) and its elongation product (eicosadienoic acid) (20:2 (n-6)) were
      predominantly incorporated into phosphatidylcholine. However, 22:6(n-3) was
      incorporated more selectively into phosphatidylethanolamine than 18:2(n-6) and
      20:2(n-6).

PMID- 9178570
TI  - Zinc finger-like motif conserved in a family of RNA binding proteins.
AB  - NP220s compose a family of RNA binding proteins together with matrin 3, one of
      major proteins of the nuclear matrix. They have repeats of RNA recognition motif
      (RRM; MH2) homologous to RRM in heterogeneous nuclear RNPs I/L in addition to MH1
      and MH3 with unknown function. In search of additional homologous sequences, we
      found the reported sequence of rat matrin 3 is partially incorrect. Correction of
      this sequence showed that the NP220 family has a fourth homologous motif with the
      characteristics of a Cys2-His2 zinc finger-like motif. The sequence of this motif
      is perfectly conserved in human and mouse NP220s despite their 75% overall
      sequence homology.

PMID- 9178571
TI  - A gene homologous to the Streptomyces chymotrypsin-like protease (SAM-p20) gene
      is tandemly located.
AB  - A gene encoding a homolog of the Streptomyces chymotrypsin-like serine protease,
      SAM-P20, was identified downstream of the sam-p20 gene and designated SAM-P20D.
      This gene has two tandem Shine Dalgarno sequences and two initiation codons. We
      have established vector systems with the function of tyrosinase gene-bone melanin
      pigmentation as a reporter for sam-p20D gene expression in Streptomyces
      coelicolor in order to identify the promoter and terminator activities. Using
      this system, the sam-p20D gene was suggested to be transcribed monocistronically.

PMID- 9178572
TI  - Peculiar archaea found in Japanese paddy soils.
AB  - Archaeal 16S rDNA clones retrieved from paddy soil DNA were sequenced. Among 100
      clones, 88 clones were assigned to methanogens and nine clones were assigned to
      crenarchaeota. However, three of the nine clones were phylogenetically far from
      the cultured crenarchaeota and closely related to marine planktonic archaea. The
      other three clones showed extremely novel 16S rDNA sequences and were
      phylogenetically far from both Crenarchaeola and Euryarchaeota. This paper
      reports the ubiquitous presence of crenarchaeotal and extremely novel clones in
      paddy soils.

PMID- 9178574
TI  - Comparison of hemisphere size in wild and domestic geese.
AB  - The hemisphere size has been studied in wild and domestic geese (Anser fabalis, n
      = 77: A. albifrons, n = 48; A. anser, n = 8; A. anser f. domestica, n = 10),
      which were classified according to particular age category (adult or immature).
      Material used in studies was fixed in 4% solution of formaldehyde. The brain
      weight as well as hemispheres' length, width and height was measured with
      standard method. Morphometric characteristic of geese's brains has been presented
      in absolute and relative way (by parallel use of index and allometric approach).
      The appropriate ontogenic, taxonomic and domestication comparisons were carried
      out. The greatest differences referred to absolute and relative width and height
      of hemispheres.

PMID- 9178573
TI  - Structure and activity of a new form of the glutamate transporter of the nematode
      Caenorhabditis elegans.
AB  - A Caenorhabditis elegans cDNA for a glutamate transporter was cloned and examined
      in this study. The predicted protein is 11 residues shorter at the N-terminus
      than Ceglut-1, which we previously reported. The protein, when expressed in
      Xenopus laevis oocytes, showed much higher glutamate transport activity than
      Ceglut-1, suggesting that the N-terminal sequence is critical in glutamate
      transport.

PMID- 9178575
TI  - Subpopulations of stromal cells from long-term human bone marrow cultures:
      ontogeny of progenitor cells and expression of growth hormone receptors.
AB  - Long-term culture of bone marrow derived stromal colony forming cells (S-CFC) in
      matrix and nutrient defined agar medium resulted in stromal cell colonies that
      pass sequentially through three distinct morphological stages: firstly,
      aggregated loose syncytium of round to avoid cells (stage I), a second
      developmental stage of large branching colonies in which the cells become
      enlarged, elongated with cytoplasmic projections forming a loosely anastomized
      network with adjacent cells (stage II), and finally cells become dissociated,
      loosing their long, thin cytoplasmic filaments and breaking their contacts with
      one another, but remain large and retain a bi-polar nature (stage III). Cells
      were also grown in liquid medium in a culture microenvironment closely resembling
      conditions of haemopoiesis in vitro. Using a panel of well defined monoclonal
      antibodies reactive against the rat, rabbit and human growth hormone receptors,
      this study found immunochemical evidence of the presence and localization of
      binding sites of growth hormone (GH) in the cell membrane and extra-nuclear Golgi
      area of long-term bone marrow derived human stromal cells in liquid and semi
      solid nutrient agar mediums. GH-receptor immunoreactivity was present in small
      proliferating progenitor cells, myofibroblast-like cells, large reticular
      fibroblast cells, adipocytes and endothelial cells. Only MAb known to be reactive
      against human tissue resulted in strong immunoreactivity. The expression of GH
      receptors not only on small proliferating, but also on the well differentiated
      cells, indicates a role for growth hormone on non-progenitor cells. GH-receptor
      immunoreactivity on differentiating and/or differentiated cells suggests that GH
      is also necessary for, or has a trophic function in differentiation. We propose
      that direct GH action is necessary not only for differentiation of progenitor
      cells as implied by the dual effector hypothesis, but also their subsequent
      clonal expansion, differentiation and maintenance.

PMID- 9178576
TI  - Presence of cerium-cytochemical reactions of glomerular phosphatases of normal
      gerbil Meriones crassus: an ultrastructural localization study.
AB  - Phosphatase cytochemical activity in the normal glomerulus of the desert gerbil
      Meriones crassus was demonstrated using cerium ions as capturing agents. Three
      major enzymes have been recognized: sodium-potassium adenosine triphosphatase
      (Na(+)-K(+)-ATPase), alkaline phosphatase (ALPase) and acid phosphatase (ACPase).
      However, cytochemical staining for these markers to map their localizations and
      distributions reveal a high positivity of Na(+)-K(+)-ATPase. This appeared as
      uniform dense precipitates surrounding the glomerular basement membrane (GBM) and
      the plasma membranes of the epithelial and endothelial cells of the glomerular
      layers. Negligible ALKase reaction product being over the glomerular epithelia
      including the GBM. In contrast, the cytochemical profiles of ACPase was unusual,
      with dense reaction products extensively covering the endoplasmic reticulum at
      the region of Golgi apparatus products lysosomes (GERL) complex, including its
      cisternal and tubular elements and the lysosomal-vacuolar apparatus of the
      glomerular epithelial cells. All other subcellular organelles showed no activity.
      For Na(+)-K(+)-ATPase, the reaction product was successive when acetate buffer
      (as decalcifying agent, pH 5.0) was used. This reaction was still seen when a
      medium containing levamisole was used. Cytochemical controls for all enzymes were
      incubated in substrate-free media including those using levamisole as an
      inhibitor of ALPase. The data presented, which is reported for the first time, is
      not an attempt to determine the contribution of the selected phosphatases in the
      glomerular physiology and pathology. Such findings may, nevertheless, have
      functional implications in the fact that these markers may be involved in the
      ultrafiltration and other metabolic activities of the glomerulus at the molecular
      and/or cellular level. In addition to earlier morphological and recent
      histochemical work, the present study updates and recognizes information to be
      used as a baseline to which the gerbil model can now be employed to investigate
      the behavioural adaptations of the desert rodents.

PMID- 9178577
TI  - Anatomy of the ductus venosus in neonatal dogs (Canis familiaris).
AB  - Anatomical features of the ductus venosus in 84 neonatal dogs are described. The
      ductus venosus was a straight conduit 1-3 mm wide and 4-12 mm long in pups with a
      crown-rump length of 80-200 mm. It arose from the left main portal vein branch
      opposite the umbilical vein, passed between the left lateral liver lobe and the
      papillary process of the caudate lobe, and terminated in the dorsal aspect of the
      proximal part of the left hepatic vein. The left hepatic vein was dilated at this
      point. There was no variation in the location of the ductus venosus in the
      animals studied.

PMID- 9178578
TI  - A quantitative study of ganglion cells in the goat retina.
AB  - As in a number of mammals, the most prominent feature of the ganglion-cell layer
      in the retina of the murciano-granadina goat is an increase in the density of
      ganglion cells in the central area, as well as a concentration along a ridge
      extending horizontally across the retina, below the optic disc, and in the upper
      temporal retina. Thus, there is an area of maximum density and two streaks that
      are known as the 'horizontal' and 'vertical' streak. The isodensity lines of
      ganglion-cell distribution is toughly concentric, with their values varying from
      304 cells/mm2 in the periphery to 3592 cells/mm2 in the central area, with the
      cells densely packed. There were some individual differences amongst the animal
      studied, although all of them were purebred animals.

PMID- 9178579
TI  - Transcranial cerebral oximetry--is it clinically useless at this moment to
      interpret absolute values obtained by the INVOS 3100 cerebral oximeter?
AB  - Dynamic changes of regional cerebral oxygenation (rSO2) were measured
      simultaneously to laser Doppler flowmetry in a 35-year-old female during cerebral
      aneurysm surgery. In addition, to demonstrate the uselessness of the absolute
      values obtained by the INVOS 3100, cerebral oximeter readings from a pumpkin
      ("Styrian Cucurbita") are demonstrated. The results of the present study and of
      other reports discussed in this paper demonstrate that the INVOS 3100 cerebral
      oximeter should not be used at this moment as a measure reflecting absolute rSO2
      values. However, it seems to be relevant that the INVOS 3100 system can monitor
      the dynamic changes in rSO2, although limitations have to be taken into
      consideration.

PMID- 9178581
TI  - The carotenoid pigments of a marine Bacillus firmus strain.
AB  - As carotenoids have important biological functions, it is important to discover
      new natural sources of these pigments. The bacterial strains isolated from a sea
      water rock pool were cultivated on marine agar containing yeast extract and
      identified by conventional methods. The bacterial pigments were extracted with
      methanol and analyzed by reversed-phase HPLC with diode array detection. The
      major pigment of a Bacillus firmus strain was identified as astaxanthin; the
      results obtained suggest potential use of this bacterium in aquaculture and in
      pharmaceutical field.

PMID- 9178580
TI  - Reorganization of contractile systems and protein tyrosine phosphorylation in
      platelet aggregation.
AB  - Platelet aggregation is accompanied with reorganization of contractile systems.
      This event involves tyrosine phosphorylation of various proteins. When tyrosine
      phosphorylation is induced by an intracellular trigger as vanadate, a
      phosphorylated cytosolic 60 Kd protein acts as a nucleating center on which new
      actin filaments grow. When aggregation is induced by an extracellular signal as
      ristocetin, actin filaments of the membrane-associated skeleton and the 60 Kd
      protein bound to this structure migrate toward the cytosol and only in this
      soluble state the 60 Kd protein undergoes tyrosine phosphorylation and
      consequently triggers reorganization of contractile systems.

PMID- 9178582
TI  - Changes of glycosaminoglycan composition in aging chicken brain. A preliminary
      investigation.
AB  - The qualitative and quantitative pattern of GAGs was examined by electrophoresis
      in aging chicken brain in four different stages starting from day 1 to 30 months.
      GAG content referred to defatted dry tissue exhibits constant decrease. Four main
      GAGs have been identified with a mobility corresponding to hyaluronate,
      condroitin sulfate, heparan sulfate and dermatan sulfate controls. Hyaluronate
      appears the main GAG represented while dermatan sulfate the minor one. Our data
      show that in chicken brain GAG percentage undergoes age-related changes.

PMID- 9178583
TI  - Assay of total protein kinase activity in mouse brain cortex.
AB  - In previous studies we demonstrated that the adrenergic system is impaired in old
      animals and that the main alterations were observed at the level of receptor
      density and adenylate-cyclase activity. The decreased ability to produce cAMP
      could influence the activity of the cAMP dependent protein kinase (PKA), one of
      the enzymes responsible for the phosphorylation of protein substrates. Since
      protein phosphorylation is one of the most common and important mechanisms
      through which a cell regulates its activity, the characteristics of the
      phosphorus incorporation reaction were studied. Kinase activity was measured in
      homogenate of young mouse brain cortex prepared avoiding gross manipulations in
      order to maintain conditions as close to those present in the living animal as
      possible. Results show that phosphate incorporation is proportional to protein
      content and strictly dependent on ATP availability. Increasing the ATP
      concentration from 10 to 500 mumol/l, the length of incorporation phase
      increases, suggesting that the limiting point of the reaction is better
      represented by energy availability than by enzyme or protein substrate
      concentrations.

PMID- 9178584
TI  - Choline feeding depresses the phospholipase C activity in the regenerating liver
      of female rats.
AB  - The administration of an excess of choline for 3 weeks is able to delay the
      proliferative response to partial hepatectomy (PH) in female rats. Choline
      feeding can affect the phospholipid composition of cell membranes and, as a
      consequence, the transduction of the mitogenic signals. On these bases, we
      studied the turnover of phosphatidylinositol-4,5-biphosphate (PIP2) in the
      regenerating liver of female rats. The hydrolysis of PIP2 is catalysed by a
      specific phospholipase C (PL-C) and it generates the second messenger molecules,
      namely diacylglycerol and inositol-1,4,5-triphosphate (IP3). Our results showed
      that the administration of an excess of choline to females was able to reduce the
      PL-C activity and the membrane IP3 content in the quiescent liver. Both
      parameters remained lower than controls during liver regeneration, even if they
      were higher 1 and 2 h after PH in comparison with the quiescent liver, in choline
      fed females. These data suggest that the delay in the liver regeneration by
      choline is due, at least in part, to the alteration in the pathway of PIP2
      turnover for the transduction of mitogenic signals.

PMID- 9178585
TI  - Changes in plasminogen activator inhibitor-1 levels in non-small cell lung
      cancer.
AB  - Increased urokinase plasminogen activator (uPA) levels are increased in a number
      of malignancies and have been correlated with decreased disease-free interval and
      decreased overall survival. We have, therefore, examined components of this
      plasminogen activating system in patients with Non-Small Cell Lung Cancer
      (NSCLC). Levels of uPA, urokinase-plasminogen activator receptor (uPAR) and
      plasminogen activator inhibitor-1 (PAI-1) were measured semiquantitatively in
      paraffin sections of tumours from 147 patients with NSCLC. Immunohistochemically
      stained sections of tumour were allocated a score for stain intensity and results
      correlated to: survival; tumour stage(T); nodal stage(N); stage grouping (I to
      IIIb), survival status and sex. Increased levels of PAI-1 were associated with a
      decreased survival in squamous cell carcinoma (SCC) X2 = 5.72, p = 0.017 (n =
      74). There was a significant positive relationship between PAI-1 levels and N
      stage (p = < 0.05), presence of nodal metastases (p = < 0.05), stage grouping (p
      = < 0.01) and extent of disease (p = < 0.05) in the total group and the SCC
      subgroup, but not adenocarcinoma. There was a significant positive relationship
      between PAI-1 levels and T-stage (p = < 0.05) in the total group, and survival
      status (p = < 0.05) in the SCC subgroup alone. uPA and uPAR levels were not
      significantly associated with tumour staging or survival. We conclude that
      increased PAI-1 antigen levels may be associated with a decreased survival in
      patients with SCC.

PMID- 9178586
TI  - Management of infected total knee arthroplasty.
AB  - BACKGROUND: Deep wound infection after total knee arthroplasty is an infrequent
      but very serious complication. Treatment is difficult and challenging. Antibiotic
      therapy alone can not replace surgery in the management of infected total knee
      arthroplasty. METHODS: Fourteen infected total knee arthroplasties in 13 patients
      were treated by the author. Nine patients underwent two-stage reimplantation, one
      patient one-stage reimplantation, one patient arthroscopic debridement, and one
      patient knee fusion. Four knees in three patients were excluded because of less
      than 12 months follow-up. This study retrospectively analyzed the results of
      treatment in 10 infected total knee arthroplasties in 10 patients. RESULTS: All
      patients were followed up for 12 months or longer. The length of follow-up ranged
      from 12 months to 69 months with an average of 28 months. All infections were
      successfully controlled, and there was no recurrence of infection. However, only
      67% of the patients showed satisfactory functional results. CONCLUSION: Based
      upon the results in this study, most of the infection after total knee
      arthroplasty could be successfully controlled by combined surgical treatment and
      intravenous antibiotic therapy. The result of two-stage reimplantation was more
      consistent and predictable. The functional result of infected total knee
      arthroplasty was less satisfactory as compared with that of the non-infected
      counterpart. Furthermore, the impact of infection or the longevity of total knee
      prosthesis could only be determined by long-term follow-up.

PMID- 9178587
TI  - Comparison of the clinical diagnostic value between pleural needle biopsy and
      analysis of pleural effusion.
AB  - BACKGROUND: Many diseases are manifested by pleural effusion. Chest echo-guided
      thoracentesis and pleural biopsy are the two major procedures in diagnosing
      pleural effusion, but the validity is still under debate. To compare the
      diagnostic value of echo-guided pleural biopsy with pleural effusion analysis, we
      designed this retrospective study. METHODS: We reviewed 176 patients who
      underwent both procedures at Chang Gung Memorial Hospital from 1989 to 1990.
      RESULTS: Sixty-six patients (38%) were diagnosed with malignant pleural effusion
      which was proven by needle biopsy (55%) or effusion cytologic analysis (64%).
      Combining both methods increased the diagnostic rate to 88%. Among the 76
      patients who were diagnosed with tuberculous pleural effusion, only 18% were
      proven by pleural biopsy and 20% by pleural effusion culture. The other cases
      were confirmed by sputum exam (34%) or successful therapeutic trial (41%). The
      remaining 19 patients (11%) were diagnosed as undeterminate etiology. CONCLUSION:
      Combined pleural biopsy with cytologic analysis of the pleural effusion was more
      beneficial than any single method in identifying malignant pleural effusions, and
      repeated pleural biopsy increased the positive rate from 49% to 55% in our study.

PMID- 9178588
TI  - Hyperbaric oxygen in the treatment of diabetic foot infection.
AB  - BACKGROUND: Although hyperbaric oxygen therapy to treat diabetic foot lesions has
      been approved for insurance reimbursement in Taiwan, its clinical application has
      not yet been well accepted. This study evaluated multiple healing predictive
      factors in patients with diabetic foot infections to determine the usefulness of
      adjunctive hyperbaric oxygen in the treatment of such patients. METHODS: From
      March 1995 to May 1996, we treated 31 diabetic patients presenting with infected
      foot lesions with a regimen of adequate metabolic control, frequent wound
      debridement and hyperbaric oxygen therapy. Age, gender, leukocyte count, total
      lymphocyte count, hemoglobin, erythrocyte sedimentation rate (ESR), c-reactive
      protein (CRP), glycosylated hemoglobin Alc (HbAlc), albumin, ankle-brachial
      index, types of bacterial cultures and number of debridements were compared
      between successful and failed treatments. Independent t-test and Fisher's exact
      test were used to identify the prognostic factors associated with outcome of
      treatment. RESULTS: The mean age of the patients was 63.0 +/- 9.7 years (range 43
      to 81). The mean number of hyperbaric oxygen therapies was 35.3 +/- 21.8
      treatments (range 5 to 83). Of the 31 patients, 6 received below knee amputation,
      and 25 had their foot preserved or achieved a lower level of amputation. Elevated
      leukocyte count and low ankle-brachial index were significantly related to poor
      outcome. CONCLUSIONS: In the treatment of diabetic foot infection, adjunctive
      hyperbaric oxygen therapy seems to be a useful tool to enhance wound healing
      provided that there are preserved circulation and controlled infection.

PMID- 9178590
TI  - Necrotizing enterocolitis in newborn: nine years' experience.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most significant acquired
      gastrointestinal (GI) emergency in the neonatal intensive care unit. METHODS: We
      sought to gain a clinical perspective on NEC by reviewing the records of NEC
      patients over a 9-year period. The case histories of 22 infants with NEC treated
      from September 1, 1986 to September 1, 1995 were reviewed. RESULTS: Mean
      gestational age was 32 weeks and mean birth weight was 1774 grams. Eighteen
      percent were full term babies and 82% were premature. Average age at the onset of
      NEC was 11 days. The most common clinical manifestations were abdominal
      distension (100%), gastric retention (64%), unstable vital signs (59%) and Guaiac
      positive vomitus or stool (36%). Sixteen cases (73%) were classified as stage III
      NEC, which has the highest mortality and/or morbidity. CONCLUSION: Early
      identification and management are critical to improve the outcome of NEC.

PMID- 9178589
TI  - Diagnosis of prostate cancer: comparison of serum prostate specific antigen,
      digital rectal examination and transrectal ultrasonography.
AB  - BACKGROUND: While prostate specific antigen (PSA) is useful as a tumor marker for
      monitoring patients with prostate cancer after definitive therapy, limitations
      have been noted when it is used for early detection of prostate cancer. METHODS:
      We reviewed the charts of 121 patients who had undergone prostate needle
      biopsies, documented digital rectal examination (DRE) and serum PSA determination
      before biopsy from January 1993 to October 1994. Indications for biopsy included
      abnormal DRE. PSA level greater than 4.0 ng/ml or abnormal lesions on transrectal
      ultrasonography (TRUS). RESULTS: Seventeen patients (14%) had stage A carcinoma
      with normal DRE and PSA levels from 0.1 to 34.9 ng/ml (mean 9.0 ng/ml). Four
      patients (3%) had stage B carcinoma with an average PSA level of 32.3 ng/ml and
      less than one lobe indurated on DRE. Six patients (5%) had stage C carcinoma and
      had an average PSA level of 48.5 ng/ml and less than one lobe indurated on DRE.
      Ninety-four (78%) patients had stage D carcinoma with an average PSA level of 120
      ng/ml and more than one lobe indurated on DRE. While hypoechoic sectors were more
      than twice as likely as isoechoic sectors of the prostate to contain malignancy
      on biopsy, nearly 20% of cancers were found in isoechoic sectors. CONCLUSION:
      Serum PSA is the most accurate of the three diagnostic tests evaluated. The
      addition of DRE or TRUS improves the detection rate of prostate cancer over PSA
      alone.

PMID- 9178591
TI  - Ketoacidosis with hyperglycemia in heavy drinkers: a report of 12 cases.
AB  - BACKGROUND: Heavy alcohol intake (> 45 g daily) might be a cause of diabetes. The
      short-term risks of heavy alcohol intake include ketoacidosis, glucose
      intolerance and pancreatitis. Alcoholic ketoacidosis (AKA) in combination with
      hyperglycemia mimics diabetic ketoacidosis (DKA). We described the
      characteristics of heavy drinkers with ketoacidosis and hyperglycemia but without
      a prior history of diabetes. METHODS: Twelve habitually heavy drinkers who had
      not been previously diagnosed as diabetes were identified by reviewing the
      records of diabetic patients admitted to Chang Gung Memorial Hospital from 1989
      to 1992. All of them met DKA criteria. RESULTS: Elevated glycohemoglobulin
      (HbAlc) level is an indicator for the diagnosis of diabetes. Among these 12
      patients, 10 had elevated levels of HbAlc and 2 had normal HbAlc levels. Of these
      2 patients, 1 had an elevated level of HbAlc 6 months later; the other who was a
      female who after observation, had normal levels of HbAlc and glucose for the
      follow-up of two years. CONCLUSION: We found that most heavy drinkers with both
      ketoacidosis and hyperglycemia also had diabetes as indicated by high levels of
      HbAlc. The only female patient had normal HbAlc and was diagnosed as AKA rather
      than DKA.

PMID- 9178592
TI  - Endoscopic sinus surgery for the treatment of frontoethmoidal mucocele
      complicated with orbital abscess: a case report.
AB  - Mucoceles may develop after several decades following sinus surgery. They can
      progressively expand over many years and destroy the surrounding bones, which may
      result in severe complications such as orbital infection or intracranial lesions.
      A 68-year-old woman was hospitalized with the chief complaints of exacerbated
      right orbital swelling and progressive visual loss for one week in May 1995.
      Under the impression of the right frontoethmoidal mucocele complicated with
      orbital abscess, she underwent endoscopic sinus surgery for marsupialization and
      wide drainage of the mucocele. The symptoms subsided one week post-operatively
      without ophthalmological sequelae. There has been no recurrence one-year post
      operatively. Endoscopic sinus surgery is an effective treatment for
      frontoethmoidal mucocele.

PMID- 9178593
TI  - Obstetrical hysterectomy and placenta previa/accreta: three bladder injury case
      reports.
AB  - Pregnancies complicated with placenta previa and a history of cesarean section
      are well known to be at increased risk for placenta accreta. Bladder injury is
      occasionally encountered in these patients during operation. From January 1992 to
      December 1995, 25 obstetrical hysterectomy were performed at Chang Gung Memorial
      Hospital, Linkou Medical Center. Of these 25 patients three had bladder injury.
      Ultrasonography is a unique way to screen and detect prenatally the abnormal
      placentation and intraplacental lacunae. Color Doppler ultrasonic scanning
      further discloses that the lacunae are mainly venous spaces. Elevated mid
      trimester maternal serum x-fetoprotein (MSAFP) frequently leads to a suspicion of
      the abnormal placentation, and magnetic resonance imaging (MRI) can clearly
      identify the placenta accreta/increta. Uncontrollable bleeding frequently occurs
      in these patients during cesarean section, warranting emergency hysterectomy.
      Emergency obstetrical hysterectomy should be decided upon and performed by an
      experienced obstetrician. Massive hemorrhage and bladder injury are the major
      complications encountered in such operations. We review the literature and
      propose a protocol of management. As the incidence of cesarean section continues
      to rise world-wide, the problem of placenta previa/accreta is likely to become
      more common. Obstetricians should be ready to face the late sequelae of today's
      decision for cesarean section.

PMID- 9178594
TI  - Glucocorticoid remediable aldosteronism: a case report.
AB  - Glucocorticoid remediable aldosteronism (GRA) is a hereditary cause of
      mineralocorticoid hypertension. The most common presentation is asymptomatic
      hypertension. Hypokalemia, hyperaldosteronism and suppressed plasma renin
      activity are other forms of primary hyperaldosteronism. However, the aldosterone
      secretion in these patients is regulated by adrenocortico-tropic hormone (ACTH)
      rather than the reninangiotension system. Here, we report a patient with a 12
      year history of hypertension without response to any treatment until
      dexamethasone was administered. The diagnosis of GRA was confirmed by elevated
      plasma level of 18-oxocortisol, which is a unique steroid biochemical abnormality
      of this disease. In GRA, hybrid steroids (18-oxocortisol and 18-hydroxycortisol)
      are synthesized at the C-18 carbon of cortisol in a similar way as when
      corticosterone is converted to aldosterone. The gene duplication defect is on
      chromosome 8 codes for a chimerical 11 beta-hydroxylase/aldosterone synthase
      enzyme, causing ectopic expression of aldosterone synthase in zona fasiculata.
      Because this hypertension is remediable by exogenous glucocorticoid, this case
      was reported to raise attention about treatable aldosteronism.

PMID- 9178595
TI  - Color Doppler energy in prenatal diagnosis of meconium peritonitis: a case
      report.
AB  - Meconium peritonitis is an uncommon chemical peritonitis of a fetus resulting
      from antenatal bowel perforation. We reported a case of meconium peritonitis with
      pseudocystic formation diagnosed by color Doppler energy (CDE) at 34 gestational
      weeks. An echogenic substance inside a fetal abdominal mass was detected using
      ultrasound. By conventional color Doppler, there was minimal blood flow in the
      cystic wall or septums of the mass. Using CDE, bowel hyperperistalsis was
      observed in multiple small bowel loops and the region of intestinal loops into
      the mass was easily detected. Therefore, the angle independent nature of CDE will
      play a significant role in the early and accurate diagnosis of meconium
      peritonitis before birth.

PMID- 9178596
TI  - Retained vaginal gauze with unusual complication: a case report.
AB  - We report a case of a postpartum retained vaginal gauze which migrated to the
      bladder and presented as a bladder stone. The patient had received numerous
      clinical evaluations for her chronic abdominal pain, of all which failed to
      detect or indicate the presence of retained gauze. Retained surgical gauze is a
      preventable problem but continues to occur periodically. Prevention remains the
      key to this problem. The gauze packed within the vagina either after transvaginal
      surgery or delivery should be cared for as in other parts of the body. Though
      extremely rare, retained surgical gauze should be considered in the differential
      diagnosis in postpartum patients with chronic abdominal pain, irritable bladder
      symptoms or pelvic abscess.

PMID- 9178597
TI  - Vulvovaginal tuberculosis: a case report.
AB  - A rare case of vulvovaginal tuberculosis is reported. A 76-year-old woman
      presented with a painful ulcer at the posterior fourchette and lower vagina for 6
      weeks. Direct biopsy for histologic examination revealed mycobacterial infection.
      Anti-tuberculosis treatment was effective for this patient. We suggest prompt
      biopsies for suspicious vulvar or vaginal lesions.

PMID- 9178598
TI  - Attacking the attacker: gay Christians talk back.
AB  - This paper analyses the accounts constructed by 60 gay male Christians in
      partnership as stigma management strategies at the level of cognition and
      rhetoric. Four strategies are identified: (i) attacking the stigma; (ii)
      attacking the stigmatizer; (iii) use of positive personal experience; and (iv)
      use of the ontogeneric argument. These strategies are interchangeably and
      collectively used to dismiss the credibility of the institutionalized Church and
      the validity of its unfavourable official position on the issue of homosexuality.
      The effective use of these strategies demonstrates the positive personal identity
      these gay Christians have developed in this advanced stage of their moral career.

PMID- 9178599
TI  - The vision within our grasp.
AB  - This article takes stock of recent progress in human development and poverty
      reduction, drawing on the 1996 Human Development Report. It presents a vision of
      human development and targets for the twenty-first century, to provide a frame
      within which we can all work in the years ahead, and identifies three specific
      actions for IPPNW to support.

PMID- 9178600
TI  - The eight myths of Operation 'Desert Storm' and Gulf War syndrome.
AB  - Several conventional claims regarding Gulf War Syndrome are criticized: that Gulf
      War veterans are no sicker than the civilian population as a whole; that Gulf War
      Syndrome is a myth invented by the press; that GWS cannot be defined as a
      legitimate medical syndrome; that since its cause cannot be determined, it is not
      a problem associated with Operation 'Desert Storm'; that the US and UK
      governments are doing all they can to investigate and treat illness in veterans
      or deny existence of over 100,000 cases in veterans and their families; that GWS
      will settle without treatment; that the armed forces were well prepared for
      integrated conflict involving chemical and biological warfare in the Middle East,
      increasing the risk of this in the future.

PMID- 9178601
TI  - Lignocellulose Decomposition and Production of Ligninolytic Enzymes During
      Interaction of White Rot Fungi with Soil Microorganisms

PMID- 9178602
TI  - Can Simple Empirical Equations Describe the Seasonal Dynamics of Bacterioplankton
      in Lakes: An Eight-Year Study in Shallow Hypertrophic and Biologically Highly
      Dynamic Lake Sobygard, Denmark

PMID- 9178603
TI  - A Seasonal Study of Bacterial Community Succession in a Temperate Backwater
      System, Indicated by Variation in Morphotype Numbers, Biomass, and Secondary
      Production

PMID- 9178604
TI  - Environmental Factors Controlling N2 Fixation in Mediterranean Rice Fields

PMID- 9178605
TI  - Characteristics of Biofilm Assemblages in Two Contrasted Hydrodynamic and Trophic
      Contexts

PMID- 9178606
TI  - Isolation and Characterization of Thermophilic Bacillus spp. from Geothermal
      Environments on Deception Island, South Shetland Archipelago

PMID- 9178607
TI  - Influence of the Hydrological Cycle on the Bacterioplankton of an Impacted Clear
      Water Amazonian Lake

PMID- 9178608
TI  - Biocontrol of Fusarium Root Rot in the Common Bean (Phaseolus vulgaris L.) by
      using Symbiotic Glomus mosseae and Rhizobium leguminosarum

PMID- 9178609
TI  - Enhanced closed-state inactivation in a mutant Shaker K+ channel.
AB  - Many mutations that shift the voltage dependence of activation in Shaker channels
      cause a parallel shift of inactivation. The I2 mutation (L382I in the Shaker B
      sequence) is an exception, causing a 45 mV activation shift with only a 9 mV
      shift of inactivation midpoint relative to the wildtype (WT) channel. We compare
      the behavior of WT and I2 Shaker 29-4 channels in macropatch recordings from
      Xenopus oocytes. The behavior of WT channels can be described by both simple and
      detailed kinetic models which assume that inactivation proceeds only from the
      open state. The behavior of I2 channels requires that they inactivate from closed
      states as well, a property characteristic of voltage-gated sodium channels. A
      detailed "multiple-state inactivation" model is presented that describes both
      activation and inactivation of I2 channels. The results are consistent with the
      view that residue L382 is associated with the receptor for the inactivation
      particles in Shaker channels.

PMID- 9178610
TI  - Regulation of cation-selective channels in liver cells.
AB  - In liver cells, cation-selective channels are permeable to Ca2+ and have been
      postulated to represent a pathway for receptor-mediated Ca2+ influx. This study
      examines the mechanisms involved in the regulation of these channels in a model
      liver cell line. Using patch-clamp recording techniques, it is shown that channel
      open probability is a saturable function of cytosolic [Ca2+], with half-maximal
      opening at 660 nm. By contrast, channel opening is not affected by membrane
      voltage or cytosolic pH. In intact cells, reduction of cytosolic [Cl-], a
      physiological response to Ca2+-mobilizing hormones and cell swelling, is also
      associated with an increase in channel opening. Finally, channel opening is
      inhibited by intracellular ATP through a mechanism that does not involve ATP
      hydrolysis. These findings suggest that opening of cation-selective channels is
      coupled to the metabolic state of the cell and provides a positive feedback
      mechanism for regulation of receptor-mediated Na+ and Ca2+ influx.

PMID- 9178611
TI  - Ethanol activates maxi Ca2+-activated K+ channels of clonal pituitary (GH3)
      cells.
AB  - The effect of ethanol on maxi Ca2+-activated K+ channels (BK channels) in GH3
      pituitary tumor cells was investigated using single-channel recordings and
      focusing on intracellular signal transduction. In outside-out patches, ethanol
      caused a transient concentration-dependent increase of BK-channel activity. 30 mm
      (1.4 per thousand) ethanol significantly increased mean channel open time and
      channel open probability by 26.3 +/- 9% and 78.8 +/- 10%, respectively; single
      channel current amplitude was not affected by ethanol. The augmenting effect of
      ethanol was blocked in the presence of protein kinase C (PKC) inhibitors
      staurosporine, bisindolylmaleimide, and PKC (19-31) pseudosubstrate inhibitor as
      well as by AMP-PNP (5'-adenylylimidodiphosphate), a nonhydrolyzable ATP-analogue,
      but not by the phospholipase C blocker U-73122. Phosphatase inhibitors
      microcystin-LR and okadaic acid promoted the ethanol effect. The blocking effect
      was released at higher concentrations of ethanol (100 mm) suggesting a second
      site of action or a competition between blockers and ethanol. Our results suggest
      that the effect of ethanol on BK-channels is mediated by PKC stimulation and
      phosphorylation of the channels which increases channel activity and hence may
      influence action potentials duration and hormone secretion.

PMID- 9178612
TI  - Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle.
AB  - The mechanisms underlying skeletal muscle functional impairment and structural
      changes with advanced age are only partially understood. In the present study, we
      support and expand our theory about alterations in sarcolemmal excitation
      sarcoplasmic reticulum Ca2+ release-contraction uncoupling as a primary skeletal
      muscle alteration and major determinant of weakness and fatigue in mammalian
      species including humans. To test the hypothesis that the number of RYR1
      (ryanodine receptor) uncoupled to DHPR (dihydropyridine receptor) increases with
      age, we performed high-affinity ligand binding studies in soleus, extensor
      digitorum longus (EDL) and in a pool of several skeletal muscles consisting of a
      mixture of fast- and slow-twitch muscle fibers in middle-aged (14-month) and old
      (28-months) Fisher 344 Brown Norway F1 hybrids rats. The number of DHPR, RYR1,
      the coupling between both receptors expressed as the DHPR/RYR1 maximum binding
      capacity, and their dissociation constant for high-affinity ligands were
      measured. The DHPR/RYR1 ratio was significantly reduced in the three groups of
      muscles (pool: 1.03 +/- 0.15 and 0.80 +/- 0.11, soleus: 0.44 +/- 0. 12 and 0.26
      +/- 0.10, and EDL: 0.95 +/- 0.14 and 0.68 +/- 0.10, for middle-aged and old
      muscles, respectively). These data support the concept that DHPR-RYR1 uncoupling
      results in alterations in the voltage-gated sarcoplasmic reticulum Ca2+ release
      mechanism, decreases in myoplasmic Ca2+ elevation in response to sarcolemmal
      depolarization, reduced Ca2+ supply to contractile proteins and reduced
      contraction force with aging.

PMID- 9178613
TI  - Identification of anion-selective channels in the basolateral membrane of
      mitochondria-rich epithelial cells.
AB  - Epithelial cells of toad (Bufo bufo) skin were isolated by treatments of the
      epidermis with collagenase and trypsin. Cl- channels in the basolateral membrane
      from soma or neck of mitochondria-rich cells were studied in cell-attached and
      excised inside-out configurations. Of a total of 87 sealed patches only 28 (32%)
      were electrically active, and in these we identified four different types of Cl-
      channels. The two major populations constituted Ohmic Cl- channels with limiting
      conductance (gamma125/125) of 10 pS and 30 pS, respectively. A much rarer 150 pS
      Ohmic Cl- channel was also characterized. From i/V relationships of individual
      channels the following Goldman-Hodgkin-Katz permeabilities were calculated, 2.2
      (+/-0.1) x 10(-14), 5.7 (+/-0.7) x 10(-14), and 32 (+/-2) x 10(-14) cm3/sec, for
      the 10, 30 and 150 pS Cl- channels, respectively. The 30 pS channel was activated
      by hyperpolarization. The gating kinetics of the 150 pS channel was complex with
      burstlike closures within openings of long duration. The fourth type of Cl-
      channel was studied in patches generating 'noisy currents' with no discrete
      single-channel events, but with vanishing fluctuations at pipette potentials near
      ECl. Noise analysis revealed a power spectrum with cutoff frequencies of 1.2 and
      13 Hz, indicating that resolution of kinetic steps was limited by small channel
      currents rather than fast channel gating. From the background noise level we
      estimated the channel conductance to be less than 1.7 pS. Despite the fact that
      the majority of patches did not contain electrically active Cl- channels, patches
      being active, generally, contained more than a single active channel. Thus, for
      the above three types of resolvable channels, the mean number of active channels
      per patch amounted to 2.1, 1.4, and 2.0, respectively. This observation, like the
      finding of few patches with several unresolvable channels, indicates that
      electrically active Cl- channels are organized in clusters.

PMID- 9178614
TI  - Regulation of metabolite flux through voltage-gating of VDAC channels.
AB  - The mitochondrial outer membrane channel, VDAC, is thought to serve as the major
      permeability pathway for metabolite flux between the cytoplasm and mitochondria.
      The permeability of VDAC to citrate, succinate, and phosphate was studied in
      channels reconstituted into planar phospholipid membranes. All ions showed large
      changes in permeability depending on whether the channel was in the open or in
      the low conductance, "closed" state, with the closed state always more cation
      selective. This was especially true for the divalent and trivalent anions.
      Additionally, the anion flux when the voltage was zero was shown to decrease to 5
      11% of the open state flux depending on the anion studied. These results give the
      first rigorous examination of the ability of metabolites to permeate through VDAC
      channels and indicate that these channels can control the flux of these ions
      through the outer membrane. This lends more evidence to the growing body of
      experiments that suggest that the outer mitochondrial membrane has a much more
      important role in controlling mitochondrial activity than has been thought
      historically.

PMID- 9178615
TI  - On the role of calcium in the regulatory volume decrease (RVD) response in
      Ehrlich mouse ascites tumor cells.
AB  - The putative role for Ca2+ entry and Ca2+ mobilization in the activation of the
      regulatory volume decrease (RVD) response has been assessed in Ehrlich cells.
      Following hypotonic exposure (50% osmolarity) there is: (i) no increase in
      cellular Ins(1,4,5)P3 content, as measured in extracts from [2-3H]myoinositol
      labeled cells, a finding at variance with earlier reports from our group; (ii) no
      evidence of Ca2+-signaling recorded in a suspension of fura-2-loaded cells; (iii)
      Ca2+-signaling in only about 6% of the single, fura-2-loaded cells at 1-mm Ca2+
      (1% only at 0.1-mM Ca2+ and in Ca2+-free medium), as monitored by fluorescence
      ratio imaging; (iv) no effect of removing external Ca2+ upon the volume-induced
      K+ loss; (v) no significant inhibition of the RVD response in cells loaded with
      the Ca2+ chelator BAPTA when the BAPTA-loading is performed in K+ equilibrium
      medium; (vi) an inhibition of the swelling-induced K+ loss (about 50%) at 1-mM
      Ba2+, but almost no effect of charybdotoxin (100 nm) or of clotrimazole (10
      microM), reported inhibitors of the K+ loss induced by Ca2+-mobilizing agonists.
      Thus, Ca2+signaling by Ca2+ release or Ca2+ entry appears to play no role in the
      activation mechanism for the RVD response in Ehrlich cells.

PMID- 9178616
TI  - Ionic permeability on isolated mouse liver nuclei: influence of ATP and Ca2+.
AB  - Patch-clamp experiments on isolated nuclei revealed the existence of ionic
      channels on the nuclear envelope, but their exact localization and function are
      still unknown. Recent studies have demonstrated that ATP and calcium ions play an
      important role in nucleocytoplasmic protein traffic. ATP is essential to allow
      big molecules in and out of the nucleus. However, a cytoplasmic rise of calcium
      ions above 300 nm decreases both ATP-dependent transport and passive diffusion
      through the nuclear envelope. The use of isolated nuclei placed in a saline
      solution provides the possibility for testing only the compounds added in the
      bath or in the recording pipette. In the present study, we show that ATP is
      responsible for an increase of nuclear ionic permeability on isolated nuclei.
      This result not only confirms data previously reported in in situ nuclei, but
      also suggests that ATP is directly involved in the modulation of passive ionic
      permeability. In these particular experimental conditions, calcium ions decrease
      the channel current starting from a concentration of 1 microM. The parallelism in
      the modulation action of ATP and Ca++ between nuclear pores and ionic channels
      present on the nuclear envelope contributes to the support of the idea that an
      ionic pathway is associated with the pore complex.

PMID- 9178617
TI  - Separate determination of the electrical properties of the tonoplast and the
      plasmalemma of the giant-celled alga Valonia utricularis: vacuolar perfusion of
      turgescent cells with nystatin and other agents.
AB  - In the giant-celled marine algae Valonia utricularis the turgor-sensing mechanism
      of the plasmalemma and the role of the tonoplast in turgor regulation is unknown
      because of the lack of solid data about the individual electrical properties of
      the plasmalemma and the vacuolar membrane. For this reason, a vacuolar perfusion
      technique was developed that allowed controlled manipulation of the vacuolar sap
      under turgescent conditions (up to about 0.3 MPa). Charge-pulse relaxation
      studies on vacuolarly perfused cells at different turgor pressure values showed
      that the area-specific resistance of the total membrane barrier (tonoplast and
      plasmalemma) exhibited a similar dependence on turgor pressure as reported in the
      literature for nonperfused cells: the resistance assumed a minimum value at the
      physiological turgor pressure of about 0.1 MPa. The agreement of the data
      suggested that the perfusion process did not alter the transport properties of
      the membrane barrier. Addition of 16 microM of the H+-carrier FCCP
      (carbonylcyanide p-trifluoromethoxyphenyhydrazone) to the perfusion solution
      resulted in a drop of the total membrane potential from +4 mV to -22 mV and in an
      increase of the area-specific membrane resistance from 6.8 x 10(-2) to 40.6 x 10(
      2) Omegam2. The time constants of the two exponentials of the charge pulse
      relaxation spectrum increased significantly. These results are inconsistent with
      the assumption of a high-conductance state of the tonoplast (R. Lainson and C.P.
      Field, J. Membrane Biol. 29:81-94, 1976). Depending on the site of addition, the
      pore-forming antibiotics nystatin and amphotericin B affected either the time
      constant of the fast or of the slow relaxation (provided that the composition of
      the perfusion solution and the artificial sea water were replaced by a cytoplasma
      analogous medium). When 50 microM of the antibiotics were added externally, the
      fast relaxation process disappeared. Contrastingly, the slow relaxation process
      disappeared upon vacuolar addition. The antibiotics cannot penetrate biomembranes
      rapidly, and therefore, the findings suggested that the fast and slow relaxations
      originated exclusively form the electrical properties of the plasmalemma and the
      tonoplast respectively. This interpretation implies that the area-specific
      resistance of the tonoplast is significantly larger than that of the plasmalemma
      (consistent with the FCCP data) and that the area-specific capacitance of the
      tonoplast is unusually high (6.21 x 10(-2) compared to 0.77 x 10(-2) Fm(-2) of
      the plasmalemma). Thus, we have to assume that the vacuolar membrane of V.
      utricularis is highly folded (by a factor of about 9 in relation to the geometric
      area) and/or contains a fairly high concentration of mobile charges of an unknown
      electrogenic ion carrier system.

PMID- 9178618
TI  - Electrophysiological actions of quinine on voltage-dependent currents in
      dissociated rat taste cells.
AB  - How taste receptor cells participate in encoding disparate compounds into
      distinct taste qualities represents a fundamental problem in the study of
      gustatory transduction mechanisms. Quinine is the most common stimulus employed
      to represent bitterness yet its electrophysiological consequences on voltage
      dependent ion channels in the taste receptor cell have not been elucidated in
      detail. This study examines such effects on taste receptor cells dissociated from
      the foliate and circumvallate papillae of the rat. Outward potassium currents,
      which include transient, sustained and calcium-activated components, were
      reversibly inhibited by bath application of quinine, with an IC50 of 5.1x10(-6)M.
      The time course of the current traces, along with voltage shifts in normalized
      conductance and inactivation curves, suggests that multiple mechanisms of
      inhibition may be occurring. Inwardly rectifying potassium currents were
      unaffected. Sodium currents, to somewhat higher concentrations of quinine (IC50 =
      6.4x10(-5)M), were also reduced in magnitude without noticeable effects on
      activation or reversal potential but with a shift in inactivation. Calcium
      currents, visualized with barium as a charge carrier, were enhanced in magnitude
      by the presence of low concentrations of quinine (10(-5)M) but were suppressed by
      higher concentrations (10(-4)M). Quinine broadened the waveform of the gustatory
      action potential and increased the input resistance. These data serve as genesis
      to future investigations of the signal transduction mechanism of quinine on
      voltage-dependent currents.

PMID- 9178620
TI  - Interference of a short-chain phospholipid with ion transport pathways in frog
      skin.
AB  - The effects of mucosal application of the short-chain phospholipid didecanoyl-L
      alpha-phosphatidylcholine (DDPC; with two saturated 10-carbon acyl chains) on
      active Na+ transport and transepithelial conductance (G) in the frog skin (Rana
      temporaria) were investigated. Active Na+ transport was measured as the amiloride
      sensitive short-circuit current (ISC) and G was determined from transepithelial
      voltage-clamp pulses under short-circuit conditions. DDPC dose-dependently
      inhibited ISC with an ID50 of about 0.05% (w/v) and a maximal effect (
      approximately 55%) at >/= 1% DDPC. G increased to steady-state values above
      control level. Simultaneously, equal increases in unidirectional sucrose
      permeabilities (PSu; measured from [14C]sucrose fluxes) were observed, and a
      positive correlation was demonstrated between DDPC-induced changes in PSu and G.
      Since amiloride did not prevent the increase in G by DDPC, these results suggest
      that the DDPC-induced increase in G represents an increase in the paracellular
      shunt conductance. The effects of mucosal DDPC were almost fully reversible
      within 8 h. The results indicate that DDPC inhibits amiloride-sensitive Na+
      channels in the apical membrane of the frog skin epithelium and opens a
      paracellular tight junction pathway. Both effects may be caused by incorporation
      of DDPC in the apical cell membrane.

PMID- 9178619
TI  - Regulation of Cl- transport by IBMX in renal A6 epithelium.
AB  - We studied regulation of Cl- transport by cAMP and Ca2+ in renal epithelial A6
      cells. Stimulation of A6 cells by 1 mM 3-isobutyl-1-methylxanthine (IBMX, an
      inhibitor of phosphodiesterase), which increased cytosolic cAMP, elicited
      biphasic increases in short-circuit current (Isc), i.e., a transient phase
      followed by a sustained one. Apical application of 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB, a Cl- channel blocker) markedly and dose
      dependently inhibited the IBMX-induced Isc. Pretreatment with nifedipine (100
      microM, a Ca2+ channel blocker) or 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'
      tetraacetic acid tetra-(acetoxymethyl)-ester (BAPTA/AM, 10 microM, a Ca2+
      chelator) partially but markedly inhibited the Isc. On the other hand, a cAMP
      dependent protein kinase inhibitor, H89 (0.5 microM for 1 h), also reduced the
      IBMX-induced Isc to a level similar to that following nifedipine or BAPTA
      pretreatment. Nifedipine had no synergistic effects on the IBMX-induced Isc in
      cells treated with H89. Ionomycin (a Ca2+ ionophore) could mimic the transient
      increase dose dependently, and H89 did not block the ionomycin-induced Isc. Taken
      together, our observations suggest that: (1) part of the IBMX-stimulated Cl-
      release is regulated by an increased cytosolic Ca2+ through nifedipine-sensitive
      Ca2+ influx; (2) cAMP-dependent phosphorylation may be required for elevation of
      the cytosolic Ca2+ concentration but not for activation of Cl- channels, which
      are directly activated by cytosolic Ca2+; and (3) the IBMX-induced sustained Cl-
      release requires cAMP elevation in addition to an increase in the cytosolic Ca2+
      concentration.

PMID- 9178621
TI  - Effects of nitric oxide on force-generating proteins of skeletal muscle.
AB  - Nitric oxide (NO) has recently been identified as a physiologically important
      intracellular messenger modulating the contractile activity of skeletal muscle
      [Kobzik L, Reid MB, Bredt DS, Stamler JS (1994) Nature 372: 546-548]. However,
      the mechanism of action of NO is not yet known. We used skinned (demembranated)
      muscle fibres to investigate the mechanism of NO function in muscle contraction.
      Maximally Ca2+-activated single fibres of rat skeletal muscle were exposed to
      physiologically relevant NO concentrations by adding NO donor molecules into the
      bath solution. Donor application caused a decline both in the contractile
      properties and in the myofibrillar adenosine triphosphatase (ATPase) activity.
      These results reveal a novel molecular mechanism of NO action: a direct
      inhibition of the force-generating proteins in skeletal muscle.

PMID- 9178622
TI  - Decline in isokinetic force with age: muscle cross-sectional area and specific
      force.
AB  - Humans produce less muscle force (F) as they age. However, the relationship
      between decreased force and muscle cross-sectional area (CSA) in older humans is
      not well documented. We examined changes in F and CSA to determine the relative
      contributions of muscle atrophy and specific force (F/CSA) to declining force
      production in aging humans. The proportions of myosin heavy chain (MHC) isoforms
      were characterized to assess whether this was related to changes in specific
      force with age. We measured the peak force of isokinetic knee extension in 57
      males and females aged 23-80 years, and used magnetic resonance imaging to
      determine the contractile area of the quadriceps muscle. Analysis of MHC isoforms
      taken from biopsies of the vastus lateralis muscle showed no relation to specific
      force. F, CSA, and F/CSA decreased with age. Smaller CSA accounted for only about
      half of the 39% drop in force that occurred between ages 65-80 years. Specific
      force dropped about 1.5% per year in this age range, for a total decrease of 21%.
      Thus, quantitative changes in muscle (atrophy) are not sufficient to explain the
      strength loss associated with aging.

PMID- 9178623
TI  - Imaging excised apical plasma membrane patches of MDCK cells in physiological
      conditions with atomic force microscopy.
AB  - We combined the patch-clamp technique with atomic force microscopy (AFM) to
      visualize plasma membrane proteins protruding from the extracellular surface of
      cultured kidney cells (MDCK cells). To achieve molecular resolution, patches were
      mechanically isolated from whole MDCK cells by applying the patch-clamp
      technique. The excised inside-out patches were transferred on freshly cleaved
      mica and imaged with the AFM in air and under physiological conditions (i. e. in
      fluid). Thus, the resolution could be increased considerably (lateral and
      vertical resolutions 5 and 0.1 nm, respectively) as compared to experiments on
      intact cells, where plasma membrane proteins were hardly detectable. The apical
      plasma membrane surface of the MDCK cells showed multiple protrusions which could
      be identified as membrane proteins through the use of pronase. These proteins had
      a density of about 90 per micron(2), with heights between 1 and 9 nm, and lateral
      dimensions of 20-60 nm. Their frequency distribution showed a peak value of 3 nm
      for the protein height. A simplified assumption - modelling plasma membrane
      proteins as spherical structures protruding from the lipid bilayer - allowed an
      estimation of the possible molecular weights of these proteins. They range from
      50 kDa to 710 kDa with a peak value of 125 kDa. We conclude that AFM can be used
      to study the molecular structures of membranes which were isolated with the patch
      clamp technique. Individual membrane proteins and protein clusters, and their
      arrangement and distribution in a native plasma membrane can be visualized under
      physiological conditions, which is a first step for their identification.

PMID- 9178625
TI  - The outer hair cell motor in membrane patches.
AB  - We have used patch-clamp techniques to record the charge movement associated with
      motility in patches of basolateral membrane from isolated outer hair cells.
      Charge movement has been measured from the voltage-dependent capacitance. Using 3
      to 4 Momega pipettes with tip diameters of 3 micron the measured maximum voltage
      dependent capacitance was 56 +/- 6 fF at -36 mV when the resting membrane
      potential was -20 mV. The calculated total charge movement was 5.6 +/- 0.6 fC (n
      = 13) and the inferred density of univalent motor elements was 8400/micron2.
      Negative pressure (applied via the pipette) increased membrane tension and
      shifted the capacitance peak to depolarised potentials. Under conditions of
      isotropic membrane stress there was no change in the peak measured capacitance in
      contrast to that measured in previous whole-cell recordings.

PMID- 9178624
TI  - Annexins from Ehrlich ascites cells inhibit the calcium-activated chloride
      current in Xenopus laevis oocytes.
AB  - The effect of annexins II, III and V, purified from different species, on the
      calcium-activated chloride current across the stage-V to stage-VI Xenopus laevis
      oocyte membrane was tested either directly, using calcium entry mediated by
      depolarization, by A23187 permeabilization of oocytes or indirectly by
      quisqualate stimulation of a metabotropic glutamate receptor in the membrane
      expressed by the oocyte after injection of mRNA. The annexins isolated from the
      Ehrlich ascites cell, which is a mouse tumor cell, were found to be potent
      inhibitors of the chloride current, showing half-maximal inhibition at 50 nM,
      whereas no block was found using bovine or porcine annexins isolated from lung
      tissue. Of the annexins tested, we found annexin III to be naturally occurring in
      the oocyte, while only trace amounts of annexins II and V could be demonstrated.
      The inhibition pattern varied somewhat according to the stimulus method, the
      inhibition being more complete when an indirect stimulus via the metabotropic
      receptor was applied compared to a direct calcium stimulus.

PMID- 9178626
TI  - Sustained GABA-induced regulation of the L-type Ca2+ conductance in crustacean
      muscle fibers.
AB  - The sustained effects of gamma-aminobutyric acid (GABA) on voltage-gated
      conductances, and excitatory and inhibitory postsynaptic currents (EPSC and IPSC,
      respectively) in crayfish opener muscle fibers were analyzed using the two
      electrode voltage-clamp technique. GABA (1.0 mM) was applied for 1-2 min and
      measurements were performed 30 min after restoring control Ringer solution. The L
      type Ca2+ current (ICa) was reduced by > 33%. The ICa conductance (gCa) was
      reduced and the activation and inactivation were slowed down by GABA. The ICa
      regulation outlasted GABA superfusion (150 min). A small decrease (< 19%) of the
      Ca2+-activated K+ current (IKCa), due to the ICa reduction, was also recorded.
      The leak (IL), the delayed-rectifier (IK) and the hyperpolarization-activated
      (IAB) currents were not affected. Picrotoxin (0.5 mM) and bicuculline (0.2 mM)
      blocked the ICa reduction. Neither the GABAB antagonist saclofen (1.0 mM) nor the
      agonist baclofen (1.0 mM) had any effect. Therefore, the ICa regulation was
      probably mediated through GABAA receptors. EPSCs, but not IPSCs, were reduced
      (30%) for prolonged periods (> 100 min.) after GABA application. We describe a
      new, potentially functional, role for GABA receptors in the mediation of a
      sustained reduction of presynaptic and postsynaptic excitability in crustacean
      muscle.

PMID- 9178627
TI  - Heart rate, blood pressure, and running speed responses to mesencephalic
      locomotor region stimulation in anesthetized rats.
AB  - The decerebrate rat locomotor preparation described in a previous study requires
      extensive brain surgery with the possibility of significant blood loss. The
      purpose of this study was to improve on the previous model by using lightly
      anesthetized instead of decerebrated rats. After initial surgery consisting of
      boring a small hole through the parietal bone, the animals were maintained on low
      levels of halothane anesthetic. The mesencephalic locomotor region was then
      located by physiological criteria using stereotaxic coordinates from the previous
      study. Locomotor speed, blood pressure and heart rate responses were then
      measured over a wide range of stimulation currents that elicited a maximal
      running speed. Stimulation currents ranged from 36 microA for walking to 82
      microA for fast galloping. Locomotor speeds ranged from 20 m/min for walking to
      64 m/min for fast galloping. Some animals easily achieved galloping speeds beyond
      100 m/min. Blood pressure and heart rate increased with increasing stimulation
      currents. Blood pressure also increased during stimulation after muscular
      paralysis. This was not due to current spread, suggesting that the mesencephalic
      locomotor region might be involved in central command mechanisms. Heart rate did
      not increase after paralysis. This supports other multi-joint dynamic studies
      suggesting that movement per se may be necessary to induce heart rate changes,
      presumably via joint mechanoreceptors. The range of locomotor patterns and
      cardiovascular responses were obtained under self-supported conditions. By
      defining the mesencephalic locomotor region via physiological criteria, and by
      grouping blood pressure and heart rate measurements by gait rather than by
      stimulation currents, the potential use of the intact model for cardiovascular
      control studies was demonstrated. The animals were able to run and gallop at high
      speeds considering they were anesthetized. The simplified preparation will be
      useful for more complex cardiovascular experiments requiring intact and self
      supported conditions.

PMID- 9178628
TI  - The direct effect of carbon monoxide on KCa channels in vascular smooth muscle
      cells.
AB  - The vasorelaxation induced by carbon monoxide (CO) has been demonstrated
      previously. Both a guanosine cyclic monophosphate (cGMP) signalling pathway and
      cGMP-independent mechanisms have been proposed to be responsible for the vascular
      action of CO. A direct effect of CO on the activity of calcium-activated K (KCa)
      channels in vascular smooth muscle cells (SMCs) and the underlying mechanisms
      were investigated in the present study. It was found that CO hyperpolarized
      single SMCs isolated from rat tail arteries. The whole-cell outward K+ channel
      currents in vascular SMCs, but not in neuroblastoma cells, were enhanced by CO.
      Extracellularly or intracellularly applied CO increased the open probability of
      single high-conductance KCa channels concentration-dependently without affecting
      the single channel conductance. Although it did not increase the resting level of
      intracellular free calcium concentration, CO significantly enhanced the calcium
      sensitivity of single KCa channels in SMCs. Furthermore, the effect of CO on KCa
      channels was not mediated by cGMP or guanine nucleotide-binding proteins (G
      proteins, Gi/Go or Gs) in excised membrane patches. Our results suggest that the
      direct modulation of high-conductance KCa channels in vascular SMCs by CO may
      constitute a novel mechanism for the vascular effect of CO.

PMID- 9178629
TI  - The response of heat shock proteins 25 and 72 to ischaemia in different kidney
      zones.
AB  - Induction of heat shock proteins (HSPs) following cell injury contributes to the
      protection of vital cell functions. It was, therefore, of interest to study the
      effects of transient renal ischaemia on the abundance and distribution of two
      HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses
      were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of
      homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of
      the rat kidney immediately after 60 min of ischaemia followed by varying periods
      of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in
      CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding
      zones of the contralateral control kidney. This initial decrease in supernatant
      HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following
      reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM,
      reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively,
      than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25
      contents had not completely normalised in CX, but had reached control levels in
      OM. In IM, the HSP25 content remained below control throughout the entire
      reperfusion period. HSP72 (supernatant) was below the detection limit in the CX
      of the control kidney. Similar to the level of HSP25, that of HSP72 was also
      markedly lower in OM and IM immediately after ischaemia. The intrarenal
      distribution of HSP72 and the sequence of zonal changes in HSP72 contents were
      similar to those observed for HSP25. These results are compatible with the view
      that, during ischaemia and the initial reperfusion period, HSP25 migrates from
      the cytoplasmic compartment (supernatant) into the nucleus and/or associates with
      cytoskeletal structures. The observation that both HSP25 and HSP72 are
      transiently induced in CX and OM, but not in IM, may be explained by the fact
      that, while all kidney cells are exposed to ischaemic stress, only inner
      medullary cells experience a major postischaemic attenuation of osmotic stress.

PMID- 9178630
TI  - Paracellular calcium transport across Caco-2 and HT29 cell monolayers.
AB  - Intestinal calcium absorption has been shown to include two processes, a
      saturable transcellular movement and a non-saturable paracellular pathway. The
      potential utility of cell monolayers for studying transepithelial intestinal
      calcium transport has already been demonstrated; however, simultaneous evaluation
      of the contribution of the saturable transcellular and of the non-saturable
      paracellular processes to the total transepithelial transport has not yet been
      attempted. The aim of this study was to investigate the contribution both of
      transcellular and paracellular transport processes to the total transepithelial
      calcium transport in two cell culture monolayers. Caco-2 cells and a clone
      derived from HT-29 cells (HT29-Cl.19A), two cell lines derived from colon
      adenocarcinomas which are known to be able to exhibit typical enterocytic
      differentiation, were used. Cell monolayers were grown on a permeable support and
      used after 15 days of culture when these cells express enterocytic
      differentiation and high transepithelial resistance. Isotopic transport rate
      measurements were performed in the absence of a chemical gradient. The
      paracellular route was evaluated using [3H]mannitol. Calcium and [3H]mannitol
      transport rates across cell monolayers were not significantly different.
      Augmentation of calcium uptake by 200 mM sorbitol did not significantly increase
      calcium or mannitol transepithelial transport; however, calcium accumulation in
      the cells was increased by about 200%. Modulation of the monolayer permeability
      by addition of 10 nM vasoactive intestinal polypeptide (VIP) or 0.5 mM carbachol
      treatment, which respectively increased and decreased the transepithelial
      resistance, consequently modified calcium and mannitol transport in a parallel
      manner. Our results show that Caco-2 and HT29-Cl.19A cell monolayers are good
      models for studying the calcium paracellular transport pathway.

PMID- 9178631
TI  - NH4+ conductance in Xenopus laevis oocytes. I. Basic observations.
AB  - Current-clamp and voltage-clamp techniques were used to study the effects of NH4+
      on the cell membrane conductance in Xenopus laevis oocytes. Superfusing the
      oocytes with NH4Cl resulted in a depolarization of the oocyte's cell membrane
      potential and, at a clamp potential of -70 mV, in an inward current. The
      magnitude of the inward current was proportional to the NH4Cl concentration in
      the extracellular solution and on membrane potential. The reversal potential,
      Erev , was -35.5 +/- 11.6 mV under control conditions and -3.1 +/- 11.0 mV (n =
      19) in the presence of NH4Cl (10 mmol/l). Superfusion of the oocytes with
      nominally Ca2+-free solution affected the NH4Cl-evoked response only marginally.
      Replacement of extracellular Na+ by N-methyl-D-glucamine+ markedly reduced, but
      did not eliminate, the NH4Cl-sensitive current and shifted the reversal potential
      to more negative potentials. The NH4Cl-induced current was substantially
      inhibited by 0.1 mmol/l flufenamate, and was less affected by blockers of the
      endogenous K+ conductance, Ba2+ and isosorbiddinitrate (ISDN). The results are
      compatible with the activation of a conductance by NH4Cl for Na+ and NH4+. The
      mechanism by which NH4Cl activates the conductance remains unknown.

PMID- 9178632
TI  - Modulation of ligand-gated dopamine channels in Helix neurones.
AB  - Dopamine gates a fast excitatory response in Helix C2 neurones. Whole cell, and
      multiple unitary dopamine-gated currents showed variable decay rates and
      desensitization properties, suggesting the presence of more than one channel
      type. Manipulation of internal free [Ca2+] by various procedures (external zero
      Ca2+ or 1 mM Co2+, prolonged depolarization, A23187, or flufenamic acid),
      affected both the amplitude and decay time for the response, and also suggested
      the presence of separate fast and slowly decaying components. Responses were
      prolonged by intracellular fluoride a non specific phosphatase inhibitor, and
      attenuated and shortened by the protein kinase inhibitors H7 and staurosporine,
      and the calmodulin inhibitor W7. Phorbol ester potentiated and prolonged the
      response and this effect was reversibly antagonized by the specific protein
      kinase C inhibitor chelerythrine. Different dopamine-activated unitary currents
      were distinguished in outside-out patches by conductance (5, 8, 12 and 15pS),
      rate of recovery from desensitization, and pattern of openings. Discrimination of
      slow and fast components of the response was possible with apomorphine, ADTN, and
      caffeine. Paradoxically the dopamine antagonists chlorpromazine and spiperone,
      but not dopamine itself, stimulated sustained activity of 5pS unitary currents
      which did not desensitize in outside-out patches. Modulation of different
      channels underlying the fast dopamine response by protein kinase C, and possibly
      other mechanisms, provides a potent means of controlling excitatory dopaminergic
      synaptic transmission.

PMID- 9178634
TI  - Force and myosin content variation in isolated intact single muscle fibres from
      Rana temporaria.
AB  - We studied the relation between force normalized by dry mass per unit length and
      the myosin fraction of muscle dry mass. The two tibialis anterior muscles were
      dissected from 12 frogs (Rana temporaria). Then, from one muscle, two single fast
      twitch fibres were isolated. Each fibre was mounted isometrically in Ringer's
      solution, and electrically stimulated using a standardized protocol. Peak force
      production, normalized by the fibre's dry mass per unit length, varied by a
      factor of 1.4. Little variation in normalized force was measured between fibres
      from the same animal, whereas between animals a significant difference was found
      (P<0.05). The contralateral muscle was used to determine the myosin fraction of
      the dry mass. The relationship between the fraction myosin of the dry mass and
      force normalized by dry mass per unit length showed a high correlation (r = 0.81;
      n = 12). From this we conclude that variation in normalized tetanic force is
      determined greatly (65%) by variations in myosin content.

PMID- 9178633
TI  - Characterization of early aldosterone-induced RNAs identified in A6 kidney
      epithelia.
AB  - The early aldosterone-induced increase in Na reabsorption across tight epithelia
      is characterized by a transcription-dependent activation of epithelial Na
      channels (ENaC) and pumps (Na,K-ATPase). In order to contribute towards the
      identification of transcriptionally regulated mediators of this process, we first
      tested mRNAs of proteins previously suggested to be involved. Epithelia were
      treated for 1 h with 10(-6 )M aldosterone, a concentration which produces a
      maximal transport response and at which both mineralo- and glucocorticoid
      receptors are occupied. Northern blot analysis showed no change in mRNAs of
      trimeric G protein alpha subunits, calmodulin, and mitochondrial energy
      metabolism proteins, whereas Na,K-ATPase alpha1 and beta1 subunit mRNAs were
      slightly increased (1.2- to 1.4-fold). In a second approach, we visualized 5000
      cDNA bands generated from A6 RNAs by differential display polymerase chain
      reaction (PCR). After 1 h of aldosterone treatment, approximately 0.5% of these
      appeared to be regulated. Four cDNA fragments corresponding to early adrenal
      steroid-upregulated RNAs (ASURs) were cloned and for two of them cDNAs containing
      entire coding sequences were isolated by library screening. ASUR4 is the Xenopus
      laevis homologue of human E16 and rat TA1, a membrane protein structurally
      related to yeast and prokaryotic permeases, and ASUR5 is the A transcript of
      Xenopus K-ras2. The rapid inductions of the four ASURs correspond to direct
      transcriptional effects since they were not inhibited by cycloheximide but were
      blocked by actinomycin D. The K1/2 values were similar or slightly below those
      reported for stimulation of Na transport. These characteristics of RNA
      accumulation and their time courses suggest a possible role of one of these
      induced RNAs in the mediation of the early effect of aldosterone on Na transport.

PMID- 9178635
TI  - Whole-cell currents from the cloned canine cardiac Na+/Ca2+ exchanger NCX1
      overexpressed in a fibroblast cell CCL39.
AB  - A conventional patch-clamp technique was used to record the whole-cell current
      from the cloned canine cardiac Na+/Ca2+ exchanger NCX1 overexpressed in a
      fibroblast cell. Ca2+ was extracellularly applied to the Na+-loaded cell to
      activate the outward current by operating the reverse mode of NCX1. No measurable
      outward current was ever elicited from the nontransfected cell. Na+/Ca2+ exchange
      blocker 5 mM Ni2+ or 3 microM KB-R7943 that was applied extracellularly abolished
      the outward current. With 140 mM external Li+ (replacing Na+), the outward
      current was transient during the Ca2+ application. In contrast, with 140 mM
      external Na+, the outward current was maintained without any inactivation during
      the Ca2+ application. I-V relations predicted from the whole-cell clamp protocols
      used were obtained both before and during the Ca2+ application. The exchanger
      whole-cell currents are thus successfully detectable from NCX1 which is
      overexpressed in this stable transfectant system.

PMID- 9178636
TI  - Augmentation of lipopolysaccharide-induced thymocyte apoptosis by interferon
      gamma.
AB  - The role of interferon (IFN)-gamma on thymocyte apoptosis in response to
      lipopolysaccharide (LPS) was investigated. The administration of LPS into mice
      induced marked apoptosis of thymocytes in vivo, but the simultaneous injection of
      anti-IFN-gamma antibody with LPS completely prevented thymocyte apoptosis.
      Pretreatment of mice with IFN-gamma markedly enhanced LPS-induced thymocyte
      apoptosis. Thymocyte apoptosis augmented by IFN-gamma occurred in the thymic
      cortex, and target cells undergoing apoptosis were CD4+8+ immature thymocytes.
      IFN-gamma itself did not induce thymocyte apoptosis in vivo and in vitro. IFN
      gamma exhibited no synergistic action with effector molecules, such as tumor
      necrosis factor (TNF)-alpha and glucocorticoids. Further, it was shown that IFN
      gamma did not enhance the susceptibility of thymocytes to apoptosis. Pretreatment
      of mice with IFN-gamma significantly augmented the serum TNF-alpha level and the
      serum cortisol level in response to LPS. Therefore, we suggest that IFN-gamma
      might augment LPS-induced thymocyte apoptosis through elevating serum TNF-alpha
      and cortisol levels.

PMID- 9178637
TI  - An analysis of alternatively spliced CD45 mRNA transcripts during T cell
      maturation in humans.
AB  - CD45 is a transmembrane protein tyrosine phosphatase found on nucleated
      hematopoietic cells. In humans, multiple protein isoforms of CD45 are produced by
      alternative mRNA splicing of exons 4, 5, and 6 coding for the extracellular
      portion. We measured all eight possible CD45 mRNA transcripts using RT-PCR in
      human thymocytes and T cell lines. We report that only six mRNA transcripts are
      present in T cells. The high mw CD45 mRNA transcripts containing exon 4
      correlated with the stage of T cell maturation: abundant high mw transcripts
      (30.7% of all CD45 mRNA transcripts) were present in immature, CD3-4-8 triple
      negative thymocytes which decreased (7.7%) in intermediate, CD4+8+ double
      positive (DP) thymocytes and then increased (13.8% or 16.8%) in mature, CD4+8- or
      CD4-8+ single-positive thymocytes. In addition, there was a complex variation in
      the spliced mRNA transcripts coding for CD45R(O), CD45R(B), CD45R(BC), CD45R(AB),
      and CD45R(ABC) protein isoforms. High mw CD45 mRNA transcripts accumulated
      immediately prior to an important physiologic event such as thymocyte expansion.
      In addition, we identified linkage between RNA splicing of exons 5 and 6, and
      splicing of exon 5 only and exons 4, 5, and 6 in FACS-purified CD4+ and CD8+
      thymocytes. These data support the developmental regulation of alternatively
      spliced CD45 mRNA transcripts and suggest that specific CD45 isoforms may play an
      important role at critical stages of T cell development.

PMID- 9178639
TI  - Polyphenols in chocolate, which have antioxidant activity, modulate immune
      functions in humans in vitro.
AB  - We studied the effects of antioxidants from chocolate, cacao liquor polyphenol
      (CLP), on human immune functions in vitro. CLP is an enriched polyphenol fraction
      purified from cacao liquor that is a major component of chocolate. It has been
      shown that polyphenols have antioxidant activity, and reactive oxygen species
      (ROS) are involved in immune responses. CLP inhibited both hydrogen peroxide and
      superoxide anion, typical ROS, production by phorbol myristate acetate-activated
      granulocytes. CLP also inhibited menadione-induced production of both hydrogen
      peroxide and superoxide anion in normal human peripheral blood lymphocytes (PBL).
      CLP treatment of normal PBL in vitro inhibited mitogen-induced proliferation of T
      cells and polyclonal Ig production by B cells in a dose-dependent manner. CLP
      treatment inhibited both IL-2 mRNA expression of and IL-2 secretion by T cells.
      These results suggest that antioxidant CLP has immunoregulatory effects.

PMID- 9178640
TI  - HLA class I-restricted and tumor-specific cytotoxic T lymphocytes from metastatic
      lymph nodes of esophageal cancers.
AB  - This paper investigates the presence of HLA class I-restricted and tumor-specific
      cytotoxic T lymphocytes (CTL) in tumor sites of esophageal cancers. Five CTL
      lines were established from the metastatic lymph nodes or pleural effusion by
      incubation with interleukin-2 of tumor-infiltrating lymphocytes: cases 1 and 5,
      HLA-A26- and HLA-A33-restricted and squamous cell carcinoma (SCC)-specific CTL;
      case 2, HLA-Cw0102-restricted and esophageal SCC-specific CTL; case 3, HLA-A24-
      and HLA-A26-restricted CTL recognizing histologically different tumor cells; and
      case 4, HLA-A26-restricted and esophageal SCC-specific CTL. These results suggest
      the existence of HLA class I-restricted and tumor-specific CTL in metastatic
      esophageal SCC.

PMID- 9178638
TI  - CD40-triggered protein tyrosine phosphorylation on Vav and on
      phosphatidylinositol 3-kinase correlates with survival of the Ramos-Burkitt
      lymphoma B cell line.
AB  - Signals transduced through CD40 rescue cells of the Ramos-Burkitt lymphoma (Ramos
      BL) B cell line from surface immunoglobulin M (sIgM)-triggered growth arrest and
      apoptosis. This study investigates whether protein tyrosine kinase (PTK) activity
      and tyrosine phosphorylation on p95(vav) and on the p85 regulatory subunit of
      phosphatidylinositol 3-kinase (PI3 kinase) play a role in the regulation of Ramos
      BL B cell survival. The PTK inhibitor herbimycin A (HA) triggers significant
      growth arrest prior to apoptosis from the G1-phase of the cell cycle, indicating
      that tyrosine phosphorylation of key proteins is critical for Ramos-BL cell cycle
      progression and survival. Indeed, signals transduced through CD40 fail to rescue
      Ramos-BL B cells from HA-triggered growth arrest and apoptosis. Since Vav and PI3
      kinase are intimately involved in the regulation of cellular growth, their
      tyrosine phosphorylation status was determined in unstimulated and anti-IgM- and
      anti-CD40-treated Ramos-BL B cells: Vav and p85 are devoid of tyrosine
      phosphorylated epitopes in control cells whereas p85, but not Vav, is
      significantly phosphorylated following ligation of sIgM and anti-CD40 triggers
      tyrosine phosphorylation on both proteins. Thus, tyrosine-phosphorylated Vav may
      be a critical effector of CD40-mediated survival. As tyrosine-phosphorylated PI3
      kinase is common to both sIgM-triggered death and CD40-triggered survival
      pathways, its lipid kinase activity was correlated with tyrosine phosphorylation
      on p85: Ramos-BL B cells exhibit high basal levels of PI3 kinase activity,
      determined by immunoprecipitation with anti-p85 and 32P incorporation into
      phosphatidylinositol, which is not significantly affected by stimulation with
      anti-IgM but which is elevated by 36 +/- 2.9% following ligation of CD40. Thus,
      tyrosine phosphorylation on p85 correlates with the CD40-triggered increase in
      PI3 kinase activity but not with basal levels nor with sIgM-triggered levels of
      enzymatic activity: these data suggest the presence of different PI3 kinase
      isoforms or the existence of multiple regulatory pathways for the same PI3 kinase
      isotype in Ramos-BL B cells.

PMID- 9178641
TI  - Expansion of an unusual population of Gr-1+CD3int cells in the lymph nodes and
      other peripheral organs of mice carrying the lpr gene.
AB  - Granulocytes and extrathymic T cells are often activated simultaneously, but they
      are absolutely separate populations in normal mice. However, some abnormal
      extrathymic T cells (i.e., CD3int cells) seen in mice carrying the lpr gene were
      found to express a granulocyte marker, Gr-1. Such mice include MRL-lpr/lpr mice
      and SCG mice. In parallel with an age-associated increase of IL-2Rbeta(low)CD3int
      cells which contained double-negative CD4-8- and B220+CD2- cells, Gr-1+CD3int
      cells increased in number in the lymph nodes and other peripheral organs. In
      addition to a major population of IL-2Rbeta(low)CD3int cells, there is a small
      population of IL-2Rbeta(high)CD3int cells which produce normal Fas mRNA and Fas
      molecule from the lpr gene. It was found that both IL-2Rbeta(low)CD3int and IL
      2Rbeta(high)CD3int cell populations contained Gr-1+ cells. IL-2Rbeta(high)CD3int
      cells tended to contain a higher proportion of Gr-1+ cells than did IL
      2Rbeta(low)CD3int cells. More interestingly, Gr-1+CD3int cells expressed a
      considerable level of mRNA of the mG-CSF receptor, similar to granulocytes. The
      present study thus yielded further information on an unusual property of
      abnormally expanding CD3int cells in mice carrying the lpr gene.

PMID- 9178642
TI  - Cytotoxic activity generated from channel catfish peripheral blood leukocytes in
      mixed leukocyte cultures.
AB  - In previous work, lysis of allotargets was routinely observed with PBL from
      nonimmune channel catfish. In the work reported here, greatly increased
      (approximately 100-fold) cytotoxic responses were generated by stimulation of
      channel catfish PBL with irradiated cells of allogeneic cloned B cell lines in
      mixed leukocyte cultures (MLC). This increased cytotoxicity did not appear to be
      simply a consequence of cell proliferation since stimulation of catfish PBL
      proliferative responses with polyclonal mitogens did not result in increased
      lysis. Somewhat surprisingly, the MLC-generated cytotoxicity did not exhibit
      allospecificity; i.e., allogeneic targets from other fish were as susceptible to
      lysis as were the cells used as stimulators. This apparent lack of
      allospecificity in MLC-generated cytotoxicity was confirmed by "cold" target
      inhibition assays. However, autologous targets were not killed, clearly
      demonstrating that MLC-generated effectors could distinguish "self" from
      "nonself" at the level of lysis/recognition. Although their origin is unresolved,
      the MLC-generated effectors may be a source of highly enriched fish cytotoxic
      cells and thus facilitate directly addressing questions pertaining to the
      evolution of such cells.

PMID- 9178643
TI  - Long-term effect of primary immunization on subsequent immune responsiveness.
AB  - Specific antigen/adjuvant combinations preferentially induce type 1 or type 2
      cytokine responses. For example, BALB/c mice primed with TNP-ovalbumin in
      complete Freund's adjuvant (TNP-OVA/CFA) produce a type 2-dominated response
      characterized by the activation of IL-4-secreting cells and the production of
      IgG1 and IgE anti-TNP antibodies. In contrast, mice primed with TNP conjugated to
      Brucella abortus (TNP-BA) produce a type 1 response dominated by the secretion of
      IFN-gamma and IgG2a anti-TNP antibodies. We examined whether treating young mice
      with these antigen/adjuvant combinations altered the cytokine profile of their
      subsequent immune responses. Mice immunized with TNP-BA and boosted several
      months later with TNP-OVA/CFA developed a cytokine and antibody profile similar
      to the priming rather than boosting antigen. This was also observed in mice
      immunized with TNP-OVA/CFA and boosted with TNP-BA. Both the ratio of IL-4:IFN
      gamma-secreting cells and the isotype of antibodies produced by these mice were
      altered by primary immunization. Analysis of Con A-responsive cells from these
      animals showed that long-lived changes in the frequency of T lymphocytes
      available to secrete type 1 versus type 2 cytokines were induced by strong
      primary immunogens.

PMID- 9178644
TI  - Th1 CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis.
AB  - Cultured cells from Micropolyspora faeni-sensitized donors can adoptively
      transfer murine experimental hypersensitivity pneumonitis (EHP). To determine
      whether the CD4+ cells responsible for transfer have characteristics of Th1 or
      Th2 cells, we established cell lines from lung-associated lymph nodes of M. faeni
      sensitized C3H/HeJ mice by culturing with antigen and either IFN-gamma, IL2, and
      anti-IL4, or IL4. Cell lines were stimulated regularly with antigen, fresh
      antigen-presenting cells, and the cytokine/anti-cytokine antibody cocktail. At
      various times after initiation of culture, cells were injected intravenously into
      recipients, which were then challenged intratracheally with M. faeni and
      sacrificed and the extent of pulmonary inflammatory response was determined. IFN
      gamma, IL4, and IL10 levels were determined in supernatants of cell cultures
      stimulated with M. faeni to characterize the cell lines as Th1 (IFN-gamma, but
      low IL4 and IL10 secretion) or Th2 (IL4 and IL10, but low IFN-gamma secretion).
      Cell lines were differentiated into either Th1 (IFN-gamma = 310 +/- 45 U/ml, IL4
      = 0.10 +/- 0.1 U/ml, IL10 = 1750 +/- 75 pg/ ml, >99% CD4+) cell lines by Day 16
      of culture or Th2 cell lines (IFN-gamma = 1.8 +/- 1.0 U/ml, IL4 = 830 +/- 388
      U/ml, IL10 = 51,700 +/- 10,900 pg/ml, >96% CD4+) by Day 30. Th1 cell lines were
      able to adoptively transfer EHP whereas Th2 cell lines were unable to adoptively
      transfer EHP. The ability to transfer EHP was directly related to the amount of
      IFN-gamma and inversely to the amount of IL4 secreted by antigen-stimulated
      cells. We conclude that it is possible to produce CD4+ cell lines with either Th1
      or Th2 characteristics from lung-associated lymph nodes of mice exposed to M.
      faeni and that only Th1 CD4+ cell lines can adoptively transfer EHP.

PMID- 9178645
TI  - CD4+ hepatic cancer-specific cytotoxic T lymphocytes in patients with
      hepatocellular carcinoma.
AB  - We investigated T cell immunity against hepatocellular carcinoma (HCC), and
      showed that both peripheral blood mononuclear cells and tumor-infiltrating
      lymphocytes incubated with interleukin-2 alone displayed HLA-nonrestricted but
      hepatic cancer-specific cytotoxicity in a majority of patients with HCC. Namely,
      they lysed both HCC and cholangiocellular carcinomas in an HLA-nonrestricted
      manner, but they did not lyse any tumors with the other histological types
      tested, normal hepatocytes, or the cells transfected with hepatitis C virus or
      MUC1 gene. These CTL lines and clones were phenotypically CD3+CD4+CD8-. These
      unique CTL could play important roles in T cell immunity against HCC.

PMID- 9178646
TI  - Characterization of a new human macrophage cell line 2MAC. 1. Expression of
      functional macrophage CD16 (Fc gammaRIIIA/gamma) and tissue factor induction on
      ligation of HLA-DR.
AB  - A human macrophage-like line, designated 2MAC, has been established from
      peripheral blood. 2MAC expresses a number of lineage-specific markers as well as
      a broad array of intercellular adhesion molecules. In particular, 2MAC expresses
      CD16/Fc gammaRIII, the low-affinity Fc receptor for IgG, as well as high levels
      of HLA class I and class II. Consistent with this macrophage assignment, we
      present evidence that 2MAC expresses the macrophage form of CD16, namely, Fc
      gammaRIIIA/gamma. By several criteria also applicable to signal transducing NK
      CD16 and T cell CD3/TCR complexes, including modulation from the cell surface and
      Ca2+ mobilization in response to ligation by specific monoclonal antibody, CD16
      expressed by 2MAC is functional. Ligation of 2MAC HLA class II, but not HLA class
      I, by specific mAb induces an increase in free cytoplasmic Ca2+ concentration
      ([Ca2+]i). This Ca2+ flux appears to be physiologically relevant, as ligation of
      HLA-DR, but not HLA class I, by mAb results in the efficient, Ca2+ mobilization
      dependent induction of tissue factor by 2MAC. 2MAC, therefore, should prove
      useful for studying signal transduction through macrophage CD16 and HLA class II.

PMID- 9178647
TI  - The antiabortive effect of progesterone-induced blocking factor in mice is
      manifested by modulating NK activity.
AB  - Immunologic effects of progesterone are mediated by a protein named the
      progesterone-induced blocking factor (PIBF), which inhibits NK activity and
      displays an antiabortive effect in mice. Our previous data provide indirect
      evidence for the importance of PIBF in the maintenance of normal gestation. This
      study was aimed at investigating whether neutralization of endogenous PIBF
      production influences pregnancy outcome and if so, what are the mechanisms that
      participate in this process. Syngeneically pregnant Balb/c mice on Day 8.5 of
      pregnancy were injected ip with 0.3 mg/kg of RU 486 or with 0.5 mg of rabbit anti
      PIBF IgG alone, or together with anti-NK monoclonal antibodies. Mice treated with
      the same amount of normal rabbit serum or untreated mice of similar gestational
      age were used as controls. On Day 10.5 the ratio of living and resorbed embryos
      and NK activity of the spleen cells were determined. In mice treated with anti
      PIBF the ratio of resorbed fetuses was significantly higher than that in
      untreated controls. In RU 486-treated mice we also observed significantly
      increased resorption rate, which was associated with the inability of spleen
      cells to produce PIBF. Both anti-PIBF treatment and that with progesterone
      receptor blocker resulted in increased splenic NK activity. There was a positive
      relationship between NK activity and the rate of resorptions. All the above
      effects were corrected by simultaneous treatment with anti-NK or anti-NC (natural
      cytotoxic) antibodies. These data allow the conclusion that PIBF contributes to
      normal gestation in mice and that the effect of PIBF is manifested via blocking
      NK and/or NC activity.

PMID- 9178648
TI  - Dopamine receptor antagonists block nerve growth factor-induced hyperactivity.
AB  - The role of dopamine receptors in mediating nerve growth factor (NGF)-induced
      locomotor stimulation was investigated by examining the effects of selective
      dopamine D1 and D2 receptor antagonists on the motor hyperactivity induced by
      NGF. A single intracerebroventricular administration of NGF (5.1 microg)
      increased locomotor activity immediately after injection in normal adult rats.
      This hyperactivity was partly blocked by the dopamine D1 receptor antagonist
      SCH23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8-
      ol) and by the dopamine D2 antagonist raclopride ((S)-3,5-dichloro-N-((1-ethyl-2
      pyrrolidinyl)methyl)-2-hydroxy-6-methoxy benzamide). Effective doses of
      raclopride did not alter spontaneous levels of activity in control rats. These
      results suggest that stimulation of both subtypes of dopamine receptors is
      necessary for eliciting NGF-induced hyperactivity in the rat. The role of the
      dopamine D2 receptor in mediating the behavioral actions of NGF appears to be
      more important than that of the dopamine D1 receptor.

PMID- 9178649
TI  - The protective effect of 2-chloroadenosine against the development of amygdala
      kindling and on amygdala-kindled seizures.
AB  - The influence of 2-chloroadenosine, a non-metabolizable adenosine A1 receptor
      agonist, was tested on the development of electrically kindled amygdala and on
      the seizure responses of fully kindled rats. Focal intra-amygdaloid injection of
      2-chloroadenosine (1-10 nmol/0.5 microl) 20 min before applying the daily
      kindling stimulus prevented the development of the kindling process. The
      behavioural seizure score and the afterdischarge duration were reduced below
      their initial values. The antiepileptogenic effects of 1 and 10 nmol of 2
      chloroadenosine were reversible 8-10 days after withdrawal of the drug. When 2
      chloroadenosine was tested on fully developed stage 5 amygdala-kindled seizures,
      it increased the generalised seizure threshold in a dose-dependent manner. A
      maximum efficiency of 125% (P < 0.001) was achieved with 5 nmol and the median
      effective dose was 0.55 nmol. Higher doses resulted in the reduced anticonvulsant
      effect (P < 0.05). With the same daily stimulation, 2-chloroadenosine 5 nmol in
      0.5 microl vehicle, significantly reduced the maximum seizure score by 90%, the
      afterdischarge duration by 88% and completely blocked the generalised seizure
      duration. The antiseizure activity of the drug lasted for 3 days. In conclusion,
      2-chloroadenosine not only acts as an anticonvulsant against electrically induced
      kindled seizures as described here, and against audiogenic seizures, electroshock
      and a variety of chemical convulsants as described by others, it prevents the
      development of the epileptic state by kindling-stimulation, i.e., it is
      antiepileptogenic. We theorise here that this is due to its blockade of
      presynaptic glutamate release.

PMID- 9178650
TI  - Duration of catalepsy correlates with increased intrastriatal sulpiride.
AB  - To investigate the mechanism underlying sulpiride-induced catalepsy, we
      simultaneously examined cataleptic behavior and the kinetics of the dopamine
      receptor antagonist, sulpiride of dopamine, and the dopamine metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC), using in vivo voltammetry. After
      intrastriatal administration of sulpiride to freely moving rats, the levels
      increased, peaked at 20 min, and remained elevated for more than 3 h. Sulpiride
      induced cataleptic behavior also continued for 3 h. Levels of DOPAC peaked 180
      min after the injection and did not return to baseline within the experimental
      period. Thus, the time-course of cataleptic behavior correlated better with
      elevated extracellular levels of sulpiride than with that of DOPAC. These
      findings suggest that sulpiride induces catalepsy via a direct action.

PMID- 9178651
TI  - The role of 5-HT(1B/1D) receptors in the modulation of 5-hydroxytryptamine levels
      in the frontal cortex of the conscious guinea pig.
AB  - The role of 5-HT(1B/1D) receptors in modulating extracellular 5-hydroxytryptamine
      (5-HT) levels in the guinea pig was investigated with the non-selective 5
      HT(1B/1D) receptor inverse agonist, methiothepin, and the selective 5-HT(1B/1D)
      receptor partial agonists, GR 127935 (n-[4-methoxy-3-(4-methyl-1
      piperizinyl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazole-3-yl)[1,1'-biphenyl]
      4-carboxamide) and GR 125743 (n-[4-methoxy-3-(4-methyl-1-piperizinyl)phenyl]-3
      methyl-4-(4-pyri dinyl)benzamide). Extracellular 5-HT levels were measured using
      the technique of brain microdialysis, in the frontal cortex of the freely moving
      guinea-pig. Extracellular 5-HT was tetrodotoxin sensitive and calcium dependent,
      and increased when perfused with a high concentration of K+. In addition,
      extracellular 5-HT levels were lowered by the 5-HT(1B/1D) receptor agonist,
      sumatriptan, and the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin, while perfusion of the selective serotonin re-uptake
      inhibitor, paroxetine, increased 5-HT in a concentration-dependent manner.
      Perfusion of methiothepin, GR 127935 and GR 125743 into the frontal cortex caused
      significant but transient increases of extracellular 5-HT. However, systemic
      administration of methiothepin, GR 127935 and GR 125743, at 0.3 mg/kg i.p.,
      produced significant decreases in extracellular 5-HT, to minima of 27 +/- 3%, 31
      +/- 12% and 27 +/- 13% of basal, respectively. The increase of extracellular 5
      HT, following 5-HT(1B/1D) receptor inverse and partial agonist perfusion into the
      frontal cortex, was probably a consequence of attenuation of an endogenous 5-HT
      tone at terminal 5-HT autoreceptors. The unexpected decrease in 5-HT levels
      following systemic administration may be a result of additional attenuation of
      endogenous 5-HT tone at cell body autoreceptors in the raphe. Such an increase in
      local 5-HT levels could then stimulate 5-HT1A receptors to inhibit cell firing
      and hence decrease 5-HT levels in the terminal regions. This was confirmed when
      co-administration of the 5-HT1A receptor antagonist, WAY 100635, significantly
      attenuated the GR 127935 decrease in 5-HT.

PMID- 9178652
TI  - The role of spinal delta1-opioid receptors in inhibiting the formalin-induced
      nociceptive response in diabetic mice.
AB  - Injection of formalin into the hindpaw of mice produced a biphasic nociceptive
      response consisting of immediate (first-phase) and tonic (second-phase)
      components. In diabetic mice, the flinching response of the first phase was
      increased while that in the second phase was decreased in diabetic mice relative
      to the results in non-diabetic mice. To examine the role of supraspinal and/or
      spinal endogenous delta1-opioid receptors in inhibiting the formalin-induced
      nociceptive response in diabetic mice, we assessed the effect of 7
      benzylidenenaltrexone, a selective delta1-opioid receptor antagonist, and
      naltriben, a selective delta2-opioid receptor antagonist, administered either
      i.c.v. or i.t., on the formalin-induced flinching response. The second-phase
      response appeared when diabetic mice were pretreated with 7-benzylidenenaltrexone
      (0.1 and 0.3 mg/kg, s.c.), but not with naltriben (0.3 and 1 mg/kg, s.c.). On the
      other hand, while 7-benzylidenenaltrexone (0.1, 0.3 and 1 microg/mouse)
      administered i.t. had no significant effect on the first phase, it significantly
      and dose-dependently increased the second phase of the formalin-induced flinching
      response in diabetic mice. 7-Benzylidenenaltrexone (1 and 3 microg/mouse)
      administered i.c.v. had no significant effect on either the first- or the second
      phase response in both non-diabetic and diabetic mice. These results suggest that
      a spinal delta1-opioid receptor-mediated endogenous antinociceptive system may
      inhibit the formalin-induced second phase of the nociceptive response in diabetic
      mice.

PMID- 9178653
TI  - Cardiac effects of isoliquiritigenin.
AB  - The effects of isoliquiritigenin on force of contraction (Fc), L-type Ca2+
      current (I(Ca)) and intracellular Ca2+ concentration ([Ca2+]i) were investigated
      in rat ventricular heart muscle. Isoliquiritigenin increased Fc and I(Ca) and,
      after longer exposure times, resting tension and [Ca2+]i. The effect of
      isoliquiritigenin (100 microM) on I(Ca) was diminished by Rp-cAMPS (30 microM).
      1H-[1,2,4]oxa- diazolo[4,3-a]quinoxalin-1-one (50 microM) did not influence the
      effects of isoliquiritigenin on Fc and I(Ca). The positive inotropic effects of
      isoprenaline and forskolin, but not of 3-isobutyl-1-methylxanthine, were
      potentiated by isoliquiritigenin (100 microM). In the presence of milrinone (10
      microM), no further effects of isoliquiritigenin (100 microM) on Fc and I(Ca)
      were observed. It is suggested that the increase in Fc and I(Ca) by
      isoliquiritigenin is due to an accumulation of cyclic AMP. These effects are
      probably unrelated to an effect of the drug on soluble guanylyl cyclase, as
      reported for smooth muscle, but rather due to a direct inhibition of
      phosphodiesterase III activity.

PMID- 9178654
TI  - Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and
      vascular factors in diabetic rats.
AB  - The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic
      acid (TAT), on the electroretinogram was determined in rats with streptozotocin
      induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2
      months, while other diabetic rats were untreated. Groups of TAT-treated and
      untreated normal rats were also studied. Treatment with TAT produced significant
      improvement of the electroretinogram. TAT shortened the peak latencies of the b
      wave oscillatory potentials, which were significantly prolonged in untreated
      diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a
      significant decrease in the retinal sorbitol and fructose concentrations (by
      46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly
      reduced ADP-induced platelet aggregation and significantly increased the red
      blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in
      sorbitol and fructose concentrations of platelet and red blood cells. There were
      significant correlations between the summed b-wave peak latencies and platelet
      aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings
      suggest that an aldose reductase inhibitor, TAT, has therapeutic value for
      diabetic retinopathy.

PMID- 9178655
TI  - Endogenous nitric oxide inhibits leukotriene B4 release from rat alveolar
      macrophages.
AB  - Effects of endogenous nitric oxide (NO) on the release of mediators of the
      lipoxygenase and cyclo-oxygenase pathway from rat alveolar macrophages were
      studied. Alveolar macrophages, freshly isolated or after 18-h culture, were
      incubated in (amino acid-free) Krebs medium and labelled with [3H]arachidonic
      acid. The release of [3H]leukotriene B4 and [3H]prostanoids (separated by high
      performance liquid chromatography) was determined. A 23187 was used as stimulus,
      as rising intracellular Ca2+ activates directly the phospholipase A2 and
      lipoxygenase pathway. A 23187 (10 microM) enhanced [3H]leukotriene B4 release
      from freshly prepared alveolar macrophages about 65-fold, but only 5- to 6-fold
      from cultured alveolar macrophages. Evoked [3H]leukotriene B4 release and
      spontaneous [3H]prostanoid release were inhibited when L-arginine (300 microM)
      was added to the Krebs incubation medium of alveolar macrophages, in which marked
      NO synthase had been induced by culture with lipopolysaccharides (10 microg/ml).
      Inhibitory effects of L-arginine were prevented by N(G)-monomethyl-L-arginine (L
      NMMA, 100 microM). Inhibition of NO synthase during the culture period by L-NMMA
      (culture medium, in contrast to Krebs medium, already contains the substrate of
      NO synthase, L-arginine), resulted in attenuation of the 'culture-dependent'
      decline of the evoked release of [3H]leukotriene B4 and allowed
      lipopolysaccharides to cause an increase in spontaneous [3H]prostanoid release
      (i.e., to induce cyclo-oxygenase activity). In conclusion, in rat alveolar
      macrophages, endogenous NO appears to inhibit the release of mediators of the
      cyclo-oxygenase and lipoxygenase pathway through multiple sites of action.

PMID- 9178656
TI  - Bradykinin-induced knee joint incapacitation involves bradykinin B2 receptor
      mediated hyperalgesia and bradykinin B1 receptor-mediated nociception.
AB  - The participation of B1 and B2 types of bradykinin receptors was studied in the
      rat knee-joint incapacitation test. Five intra-articular successive hourly
      administrations of bradykinin produced progressive incapacitation, thus
      indicating that bradykinin induced sensitization to its own nociceptive effect.
      Four co-injections of bradykinin with the bradykinin B1 receptor antagonist des
      Arg9-[Leu8]bradykinin were without nociceptive effect. However, a 5th injection
      of bradykinin alone produced intense incapacitation. The bradykinin B2 receptor
      antagonist HOE-140 ([D-Arg)[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), or indomethacin,
      prevented the bradykinin-induced incapacitation. However, successive co
      injections of bradykinin with prostaglandin E2, in contrast to bradykinin alone,
      did induce incapacitation in animals pretreated with indomethacin or HOE-140. The
      injection of the bradykinin B1 receptor agonist des-Arg9-bradykinin into
      prostaglandin E2-treated joints did induce incapacitation, although
      administration of the bradykinin B1 receptor agonist or prostaglandin E2 alone
      did not induce incapacitation. In conclusion, in ongoing articular inflammation,
      it is suggested that the bradykinin B1 receptor is particularly involved with
      nociceptor activation, while the bradykinin B2 receptor is related to nociceptor
      sensitization.

PMID- 9178657
TI  - Effects of pyrroloquinoline quinone on glutamate-induced production of reactive
      oxygen species in neurons.
AB  - Pyrroloquinoline quinone may act as a free radical scavenger and also as a
      modulator of the NMDA receptor associated redox modulatory site. Using the
      oxidation sensitive dye dihydroethidium, we examined the effects of
      pyrroloquinoline quinone on free radical production in cultured forebrain neurons
      following glutamate receptor activation. Both glutamate (100 microM) and hydrogen
      peroxide (30 mM) produced a rapid increase in dihydroethidium fluorescence
      indicating dye oxidation. Pyrroloquinoline quinone (5-200 microM) effectively
      inhibited dihydroethidium fluorescence induced by glutamate but not by hydrogen
      peroxide. Glutamate-induced dihydroethidium fluorescence was inhibited by the
      thiol oxidant 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). Pyrroloquinoline
      quinone (50 microM) inhibited glutamate responses in control and in
      dithiothreitol treated neurons. However, pyrroloquinoline quinone did not further
      decrease the response to glutamate in DTNB treated neurons. These results suggest
      that pyrroloquinoline quinone inhibits the free radical-generating response to
      glutamate by oxidizing the NMDA receptor redox site and not by scavenging
      reactive oxygen species.

PMID- 9178658
TI  - Influence of receptor density on the patterns of beta2-adrenocepter
      desensitization.
AB  - Sustained stimulation of the beta2-adrenoceptor leads to a desensitization of the
      receptor-mediated adenylyl cyclase stimulation. While desensitization promoted by
      nanomolar concentrations of isoproterenol involves the phosphorylation of the
      beta2-adrenoceptor by protein kinase A alone, both protein kinase A- and beta
      adrenoceptor kinase-mediated phosphorylation leading to the binding of beta
      arrestin contribute to the desensitization evoked by micromolar concentrations of
      agonist. In the present study, we assessed the influence of receptor density on
      the patterns of desensitization induced by these two different levels of
      stimulation. Murine L cells were transfected with a cDNA encoding the human beta2
      adrenoceptor and clonal cell lines expressing various levels of beta2
      adrenoceptor were used for the study. In cell lines expressing the highest number
      of receptor, approx. 150000 sites/cell (approx. 3000 fmol/mg of membrane
      proteins), pretreatment with micromolar concentrations of isoproterenol causes a
      desensitization pattern characterized by a reduction in both the potency and the
      efficacy of isoproterenol to further stimulate the adenylyl cyclase activity. In
      contrast, desensitization induced by 10 nM isoproterenol resulted only in a
      decrease in the potency of isoproterenol. This distinct pattern of
      desensitization is not seen in cells expressing 12000 receptors/cell (approx. 200
      fmol/mg of membrane proteins) and, in that case, pretreatment with 10 nM
      isoproterenol leads to a reduction in both the sensitivity and the maximal
      response. Similar effects on the beta-adrenoceptor-stimulated adenylyl cyclase
      were observed in these cells following treatment with dibutyryl cAMP. Receptor
      density therefore dramatically influences the pattern of desensitization evoked
      by low level of stimulation. The results also demonstrate that although different
      molecular events are involved in the desensitization evoked by different levels
      of stimulation, its phenotypic expression can be qualitatively identical in cells
      expressing a relatively small number of receptors. Hence, protein kinase A
      mediated desensitization cannot be qualitatively distinguished from the beta
      adrenoceptor kinase-mediated process in these cells.

PMID- 9178659
TI  - Characterization of metabotropic glutamate receptors in rat C6 glioma cells.
AB  - Metabotropic glutamate receptors in rat C6 glioma cells have been characterized
      by pharmacological and kinetic binding experiments, using both L-[3H]glutamate
      and [3H(+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid ([3H](+/-)-trans
      ACPD) radioligands. Saturation experiments revealed a single binding site with a
      Kd = 1250 +/- 101 nM and Bmax = 12.1 +/- 1.8 pmol/mg protein when the assays were
      performed with L-[3H]glutamate as radioligand in the presence of AMPA, kainate,
      NMDA and DL-threo-beta-hydroxyaspartic acid. When [3H](+/-)-trans-ACPD was used
      as radioligand, the kinetic parameters obtained were Kd = 2605 +/- 1042 nM and
      Bmax = 13.66 +/- 5.01 pmol/mg protein. Pharmacological characterization indicated
      that specific binding of L-[3H]glutamate was sensitive to different agonists of
      mGlu receptors, showing a rank order of affinity L-glutamate > L-quisqualic acid
      > (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) > ibotenic
      acid >>> (2S, 'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I). Specific binding
      of L-[3H]glutamate to mGlu receptors is regulated by guanine nucleotides.
      Guanylyl imidodiphosphate (Gpp(NH)p) causes an affinity shift on the L-glutamate
      dose-response curve, increasing the IC50 value. These results support the
      evidence that metabotropic glutamate receptors are present in rat C6 glioma cells
      and they are coupled to a G-protein.

PMID- 9178660
TI  - Role of glutathione metabolism in the glutamate-induced programmed cell death of
      neuronal-like PC12 cells.
AB  - In addition to its well-known interaction with ionotropic and metabotropic
      receptors, glutamate may, at high concentrations, interfere with a cystine
      glutamate antiport designated as Xc- and lead to a significant decrease in
      cystine uptake and intracellular glutathione level. These effects, in turn, may
      induce death in various cellular bodies including astrocytes, rat glioma cells
      and cortical neurons in culture. In the present paper we demonstrate that the
      toxicity evoked by glutamate in a neuronal-like model is indeed related to the
      metabolism of glutathione since glutamate toxicity is preceded by a significant
      depletion of intracellular glutathione and is abolished in the presence of
      precursors of glutathione synthesis such as cystine and N-acetylcysteine. It also
      appears that prolonged incubation in cystine-free medium leads to cell detachment
      and death, a phenomenon which is progressively abolished in the presence of
      increasing concentrations of cystine. In addition, buthionine sulfoximine, a
      known inhibitor of glutathione synthesis, also induces cell lysis with a time
      course very similar to that of glutamate. However, depletion of glutathione is
      probably not sufficient to trigger the death signal since cycloheximide, which
      inhibits the toxic effect of both glutamate and buthionine sulfoximine, does not
      block the decrease in cellular glutathione content induced by these drugs. Our
      results therefore confirm that oxidative stress and intracellular glutathione
      depletion are able to trigger programmed cell death in neuronal-like cells,
      although the exact nature of the death mechanisms remains largely unknown.

PMID- 9178662
TI  - MEN1 gene discovery may lead researchers down new pathway.

PMID- 9178661
TI  - Relative efficacies of delta-opioid receptor agonists at the cloned human delta
      opioid receptor.
AB  - The present study was conducted to determine the relative efficacies of the
      selective delta-opioid receptor agonists SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4
      allyl-2,5-dimethyl-1-piperazinyl )-3-methoxybenzyl]-N,N-diethylbenzamide), pCl
      DPDPE (cyclic[D-Pen2,4'-ClPhe4,D-Pen5]enkephalin) and (-)-TAN67 ((-)-2-methyl-4a
      alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a alpha-octahydro-quinolino-[2,3,3
      g]isoquinoline). Experiments compared the abilities of the three drugs to
      competitively inhibit [3H]naltrindole binding and also stimulate [35S]GTPgammaS
      binding in membranes prepared from stably transfected Chinese hamster ovary (CHO)
      cells that express the cloned human delta-opioid receptor. Efficacy was
      determined according to the formula: efficacy = (E(max-A)/Emax)(A'/A + 1) X 0.5.
      Results show that SNC80 and pCl-DPDPE had efficacy values that were about 6-7
      times greater than that of (-)-TAN67.

PMID- 9178663
TI  - Dues-paying docs?

PMID- 9178664
TI  - Death in the Fas lane.

PMID- 9178665
TI  - Storming the gates (the gatekeeper)

PMID- 9178666
TI  - The metamorphosis of motility: from squiggles to neuroscience.

PMID- 9178667
TI  - Image of the month. CREST syndrome: calcinosis cutis, Raynaud's phenomenon,
      esophageal dysmotility, sclerodactyly, and telangiectasis.

PMID- 9178668
TI  - Surveillance of patients with Barrett's esophagus for dysplasia and cancer with
      balloon cytology.
AB  - BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's
      esophagus is desirable. The aim of this study was to compare nonendoscopic
      balloon cytology with biopsy and brush cytology for detecting dysplasia and
      carcinoma in patients with Barrett's esophagus. METHODS: Patients in a
      surveillance program underwent balloon cytology before endoscopy with biopsy and
      brush cytology. Results of cytology were compared with those of histology.
      RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients
      with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology
      obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients
      with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia.
      Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but
      only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had
      abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade
      dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia
      (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells
      (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with
      biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade
      dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest
      that a more abrasive balloon may improve balloon cytology sensitivity. The
      potential cost savings of balloon cytology compared with endoscopic cancer
      surveillance in Barrett's esophagus support further studies of this technique.

PMID- 9178669
TI  - Speed of healing and symptom relief in grade II to IV gastroesophageal reflux
      disease: a meta-analysis.
AB  - BACKGROUND & AIMS: Esophagitis healing proportions are often incorrectly called
      the healing rate. The aim of this study was to compare different drug classes by
      expressing the speed of healing and symptom relief through a new approach.
      METHODS: A fully recursive literature search to July 1996 identified 43 articles
      on gastroesophageal reflux disease (GERD) (7635 patients) meeting strict
      inclusion criteria: single- or double-blind randomized studies in adults with
      endoscopically proven erosive or ulcerative esophagitis. For each drug class,
      linear regression analysis estimated the average percentage of patients who were
      healed and heartburn free per week. RESULTS: Mean overall healing proportion
      irrespective of drug dose or treatment duration (< or =12 weeks) was highest with
      proton pump inhibitors (PPIs; 83.6% +/- 11.4%) vs. H2-receptor antagonists
      (H2RAs; 51.9% +/- 17.1%), sucralfate (39.2% +/- 22.4%), or placebo (28.2% +/-
      15.6%). Correcting for patients without baseline heartburn, the mean heartburn
      free proportion was highest with PPIs (77.4% +/- 10.4%) vs. H2RAs (47.6% +/-
      15.5%). PPIs showed a significantly faster healing rate (11.7%/wk) vs. H2RAs
      (5.9%/wk) and placebo (2.9%/wk). PPIs provided faster, more complete heartburn
      relief (11.5%/wk) vs. H2RAs (6.4%/wk). CONCLUSIONS: More complete esophagitis
      healing and heartburn relief is observed with PPIs vs. H2RAs and occurs nearly
      twice as fast. This semiquantitative expression of speed of healing and symptom
      relief permits comparisons for future economic evaluation and quality-of-life
      assessments.

PMID- 9178670
TI  - Large paraesophageal varices on endosonography predict recurrence of esophageal
      varices and rebleeding.
AB  - BACKGROUND & AIMS: Recurrence of varices and rebleeding after endoscopic therapy
      is very common. Data on the prediction of recurrent varices after initial
      obliteration by endoscopic therapy are few. The aim of this study was to
      correlate the presence and the size of paraesophageal varices (PEVs) in patients
      after endoscopic variceal ligation with recurrent varices and rebleeding.
      METHODS: Forty patients who underwent endoscopic banding ligation for esophageal
      variceal bleeding were studied by endosonography within 4 weeks after
      obliteration of varices. PEVs were classified as none, small, or large (maximum
      diameter, > or =0.5 cm). Esophagoscopy and endosonography were then repeated
      every 6 months for up to 1 year. RESULTS: Two patients (5%) were not detected to
      have PEVs. Small and large PEVs were identified in 24 (60%) and 14 (35%)
      patients, respectively. During the follow-up period of 1-year, recurrent
      submucosal esophageal varices were detected in 24 patients, including 13 patients
      (93%) with large PEVs and 11 patients (46%) with no or small PEVs (P = 0.0019).
      Recurrent bleeding occurred in 6 patients (43%) with large PEVs and in 3 patients
      (12%) with small PEVs (P = 0.044). CONCLUSIONS: Patients with large PEVs have a
      higher risk of developing recurrent varices and rebleeding.

PMID- 9178671
TI  - Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug
      associated gastroduodenal ulceration.
AB  - BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly
      associated with gastroduodenal ulceration. How to manage patients with NSAID
      associated ulcers is a common clinical dilemma. High-dose famotidine in the
      healing and maintenance of NSAID-associated gastroduodenal ulceration was
      therefore evaluated. METHODS: One hundred four patients with rheumatoid or
      osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice
      daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer
      healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users
      with healed ulcers were then randomized to receive 40 mg twice daily famotidine
      or placebo and underwent endoscopy at 4, 12, and 24 weeks. RESULTS: Cumulative
      ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%
      95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%)
      for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer
      relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%
      70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P
      = 0.011). CONCLUSIONS: High-dose famotidine is effective ulcer healing therapy in
      patients who stop or continue NSAID treatment and significantly reduced the
      cumulative incidence of gastroduodenal ulcer recurrence compared with placebo
      when given as maintenance therapy.

PMID- 9178672
TI  - Thalidomide: a novel therapy for microsporidiosis.
AB  - BACKGROUND & AIMS: Microsporidiosis is a common cause of chronic diarrhea in
      human immunodeficiency virus (HIV)-seropositive individuals and often does not
      respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated
      in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as
      therapy. METHODS: Eighteen subjects with chronic diarrhea caused by
      Enterocytozoon bieneusi that had not responded symptomatically to albendazole and
      1 untreated subject with Encephalitozoon intestinalis received 1 month of
      thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and
      body weight, histological response by light microscopy with villus height/crypt
      depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha
      level. RESULTS: Seven subjects with chronic diarrhea due to E. bieneusi had a
      complete clinical response, and 3 had a partial response to thalidomide. There
      was a significant decrease in stool frequency from 5.3 to 3.1 per day (P =
      0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide
      significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P =
      0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha
      level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent
      disruption of all stages of the life cycle of E. intestinalis. CONCLUSIONS:
      Thalidomide may be an effective therapy for diarrhea and weight loss from E.
      bieneusi.

PMID- 9178673
TI  - The prevalence and causes of chronic diarrhea in patients with celiac sprue
      treated with a gluten-free diet.
AB  - BACKGROUND & AIMS: The majority of patients with celiac sprue experience diarrhea
      before diagnosis. There have been no studies of the prevalence or causes of
      chronic diarrhea in these patients after treatment with a gluten-free diet.
      METHODS: Seventy-eight patients with celiac sprue (59 women and 19 men) treated
      with a gluten-free diet for at least 12 months were surveyed about their bowel
      habits. Those with chronic diarrhea, defined as passage of loose stools three or
      more times per week for 6 months, underwent an extensive diagnostic evaluation to
      determine its cause. RESULTS: Sixty-two of the 78 patients (79%) experienced
      diarrhea before treatment, and 13 (17%) had chronic diarrhea (of lesser severity)
      after treatment. The causes of diarrhea in 11 patients consenting to this study
      were microscopic colitis, steatorrhea secondary to exocrine pancreatic
      insufficiency, dietary lactose or fructose malabsorption, anal sphincter
      dysfunction causing fecal incontinence, and the irritable bowel syndrome. Only 1
      patient had antigliadin antibodies detected in serum or small intestinal villous
      atrophy. CONCLUSIONS: After treatment of celiac sprue with a gluten-free diet,
      chronic diarrhea persists in a substantial percentage of patients. Although
      ongoing gluten ingestion is one possible cause, other causes may be more
      frequent. Therefore, diagnostic investigation of diarrhea in celiac sprue after
      treatment seems warranted.

PMID- 9178674
TI  - Role of pancreatic impairment in growth recovery during gluten-free diet in
      childhood celiac disease.
AB  - BACKGROUND & AIMS: Clinical significance and duration of insufficient release of
      pancreatic enzymes in childhood celiac disease have not been clarified. The aim
      of this study was to evaluate the role that pancreatic impairment plays in growth
      recovery and the duration of this impairment. METHODS: Forty-six patients with
      celiac disease who had a median age of 2.5 years were enrolled. Fecal
      chymotrypsin level was determined at diagnosis and then every 15 days after the
      beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46
      patients with celiac disease had subnormal fecal chymotrypsin values. During the
      gluten-free diet, a progressive reduction in the percentage of patients with
      subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days
      and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free
      diet was significantly greater in patients with normal fecal chymotrypsin values
      at diagnosis than in patients with subnormal values, and a positive correlation
      was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56).
      CONCLUSIONS: A small percentage of patients with celiac disease still had
      subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal
      chymotrypsin is a predictive index of weight recovery in the first months after
      diagnosis of celiac disease; it could be used to select patients for enzyme
      supplementation therapy.

PMID- 9178675
TI  - Genetic markers may predict disease behavior in patients with ulcerative colitis.
AB  - BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2
      of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and
      extensive ulcerative colitis, respectively. The aim of this study was to test
      these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA
      DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls.
      Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL
      1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil
      cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects
      by fixed neutrophil enzyme-linked immunosorbent assay and indirect
      immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients
      (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in
      patients with extensive disease (15.8%; P < 0.0001) or extraintestinal
      manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis
      (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were
      reduced in patients (P = 0.005). Differences were noted between extensive and
      distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6%
      in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of
      patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was
      increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict
      disease behavior in ulcerative colitis.

PMID- 9178676
TI  - Quantification of the placebo response in ulcerative colitis.
AB  - BACKGROUND & AIMS: There is consistently a measurable benefit noted among placebo
      users in treatment trials of ulcerative colitis (UC). The aim of this study was
      to define the placebo response in active UC and identify study features that
      influence the placebo response. METHODS: MEDLINE database was searched for
      placebo-controlled treatment studies of active UC. Data extraction was performed
      by two reviewers, and one separate investigator reviewed all trials and data
      extraction before data tabulation. Placebo remission and benefit rates were
      determined for clinical, endoscopic, and histological outcomes. Synthesis
      analysis on the weighted proportions from the different studies explored the
      placebo response as it related to eight study variables. RESULTS: Thirty-eight of
      44 studies identified were included in the analysis. The clinical remission rate
      was 9.1% (confidence interval [CI], 6.6-11.6) and the benefit rate was 26.7% (CI,
      24.1-29.2). Similar rates were observed endoscopically and histologically. The
      number of study visits (< or =3 vs. >3) modified placebo response as assessed by
      clinical benefit (P = 0.05), endoscopic remission (P = 0.02), and histological
      remission (P = 0.04). Other study variables were not significant placebo response
      modifiers. CONCLUSIONS: In trials of active UC, the placebo remission rate is
      approximately 10% and the placebo benefit rate is approximately 30%. These rates
      are consistent regardless of assessment end point. The placebo response is
      greater in trials with more frequent study visits (more than three).

PMID- 9178677
TI  - The effect of gastroenterology training on the efficiency and cost of care
      provided to patients with diverticulitis.
AB  - BACKGROUND & AIMS: National trends emphasize the need for cost-efficient medical
      care with no diminution in quality. The most appropriate role for various
      physician groups has yet to be determined. The aim of this study was to
      investigate the efficiency of medical care provided by family practitioners
      (FPs), internists (IMs), and gastroenterologists (GIs) for acute diverticulitis.
      METHODS: All medicare hospitalizations from 1990 to 1993 in Illinois caused by
      acute diverticulitis, with FPs, IMs, or GIs as the primary attending physician,
      were included in the study. RESULTS: The primary attending physician was an FP in
      1019 cases, an IM in 2535 cases, and a GI in 163 cases. The age and sex
      distributions were similar. The length of stay was significantly shorter (P <
      0.0001) for GIs (7.4 +/- 6 days) than for FPs (7.9 +/- 14 days) or IMs (8.6 +/- 7
      days). Readmission rate was significantly less (P < 0.03) for GIs (4.5%) than for
      FPs (7.7%) or IMs (10.0%). No significant differences were noted in complication
      rates or mortality. CONCLUSIONS: Patients with diverticulitis treated by GIs have
      a shorter hospital stay and a lower risk for readmission than patients treated by
      FPs or IMs. This improved quality of care should be considered by managed care
      organizations because they decide the role of various physician groups.

PMID- 9178678
TI  - Virtual colonoscopy with magnetic resonance imaging: in vitro evaluation of a new
      concept.
AB  - BACKGROUND & AIMS: Screening for colonic polyps is desirable. A new concept based
      on cross-sectional and endoscopic analysis of a magnetic resonance (MR) data set
      is presented. METHODS: Ex vivo autopsy colonic specimens, containing artificially
      placed polyps, were obtained and filled with a gadolinium-containing solution.
      Forty-four thin-section MR images were obtained in a 1.5-T MR scanner in 28
      seconds. A three-dimensional endoscopic fly-through of these images was rendered.
      Fly-throughs and two-dimensional cross-sectional images were analyzed by two
      observers for the presence of polyps. RESULTS: The average sensitivity and
      specificity for the detection of polyps based on three-dimensional endoscopic MR
      colon imaging were 87% and 96%, respectively. Analysis of cross-sectional images
      showed an overall sensitivity and specificity of merely 57% and 84%,
      respectively. The difference in the interpretation of three-dimensional MR
      colonoscopy and two-dimensional cross-sections was statistically significant (P <
      0.001). With three-dimensional MR colonoscopy, overall sensitivity for detection
      of polyps measuring < or =5 mm in length and diameter was 70%; for larger polyps,
      it increased to 95% (P < 0.01). CONCLUSIONS: The feasibility of an MR-based
      endoluminal assessment of the colon is shown. Minimal invasiveness, lack of
      radiation exposure, and high in vitro diagnostic accuracy warrant further
      investigation of this novel concept.

PMID- 9178679
TI  - Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa
      associated lymphoid tissue lymphomas.
AB  - BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and
      progression of gastrointestinal mucosa-associated lymphoid tissue (MALT)
      lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor
      suppressor gene in MALT lymphomas of the stomach and colon. METHODS: Tumor
      samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n
      = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA
      was extracted from microdissected areas with at least 80% tumor cells. To detect
      homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was
      used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated
      sequence as internal control. RESULTS: Homozygous p16 deletions were found in 2
      of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had
      Helicobacter pylori-associated gastritis; however, DNA extracted from areas of
      gastritis showed a normal p16 complement. No deletion was found in any of the low
      grade gastric or the colonic MALT lymphoma specimens. CONCLUSIONS: In a subset of
      gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute
      to the transformation from a low-grade to a high-grade malignancy.

PMID- 9178680
TI  - CD4+ T-cell population mediates development of inflammatory bowel disease in T
      cell receptor alpha chain-deficient mice.
AB  - BACKGROUND & AIMS: Increase of T cells expressing CD4 and T-cell receptor (TCR)
      alpha- beta+ (beta[dim]) was observed in the mucosal and peripheral lymphoid
      tissues of TCR alpha-/- mice with inflammatory bowel disease (IBD). The aim of
      this study was to characterize the CD4+ TCR alpha-beta+ T cells. METHODS:
      Cytokine production, TCR V beta usage, and helper function for Peyer's patch B
      cells by the CD4+ TCR alpha-beta+ T cells were assessed. RESULTS: The CD4+ TCR
      alpha-beta+ T cells purified from mesenteric lymph nodes and lamina propria of
      the intestine of IBD mice exclusively produced interleukin 4, used selected
      subsets (V beta6, V beta8, V beta14, and V beta15) of TCR, and massively
      proliferated after stimulation with staphylococcal enterotoxin B. Addition of the
      CD4+ TCR alpha-beta+ T cells to Peyer's patch B-cell cultures markedly enhanced
      immunoglobulin (Ig) A, IgG, and IgM antibody responses. Furthermore, depletion of
      the TCR alpha-beta+ T cells with monoclonal antibody against TCR beta chain
      completely suppressed the onset of IBD and polyclonal B-cell activation in the
      TCR alpha-/- mice. CONCLUSIONS: These findings suggest the CD4+ TCR alpha-beta+ T
      cells-mediated development of IBD in TCR alpha-/- mice.

PMID- 9178681
TI  - Early functional effects of Clostridium difficile toxin A on human colonocytes.
AB  - BACKGROUND & AIMS: Previous in vitro studies have shown that Clostridium
      difficile toxin A is able to directly affect the intestinal epithelial barrier
      function. The aim of this study was to examine the early effects of toxin A on
      mucin exocytosis and determine whether this toxin can induce the production of
      the chemokine interleukin 8 (IL-8) from human colonic epithelial cells. METHODS:
      Two model systems were used: the HT29-CI.16E colonic goblet cell line and primary
      cultures of human normal colonocytes. RESULTS: Toxin A exerted a rapid and dose
      related inhibition of stimulated mucin exocytosis without altering baseline
      (constitutive) mucin exocytosis from HT29-CI.16E cells. Toxin A was also able to
      induce the secretion of IL-8 from both HT29-CI.16E cells and primary cultures of
      human normal colonocytes, as early as 2-3 hours of incubation. CONCLUSIONS: The
      results show that while toxin A is able to down-regulate stimulated mucin
      exocytosis, it is able to up-regulate the secretion of an important
      chemoattractant chemokine, IL-8. These modifications illustrate the ability of
      colonocytes to recruit inflammatory and immune cells that will eventually bring
      about major mucosal damage.

PMID- 9178682
TI  - Enhanced leukocyte binding by intestinal microvascular endothelial cells in
      inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Microvascular endothelial cells mediate leukocyte homing,
      angiogenesis, and inflammation and healing and show tissue-specific adhesion
      molecules and functions. The activation of human intestinal mucosal microvascular
      endothelial cells (HIMECs) was studied in vitro to uncover possible abnormalities
      associated with inflammatory bowel disease. METHODS: HIMECs were isolated from
      normal and inflammatory bowel disease mucosa and assessed for phenotypic and
      morphological features, proliferative response, leukocyte binding capacity, and
      adhesion molecule expression. RESULTS: Basal proliferation by HIMECs was less
      than that of human umbilical vein endothelial cells (HUVECs) but increased
      proportionally more in response to vascular endothelial growth factor.
      Proinflammatory stimuli induced an activated, spindle-shaped morphology in HIMEC
      monolayers. Compared with HUVECs, unstimulated HIMECs showed less adhesiveness
      for U937 and MOLT4 cells and neutrophils, but cytokines and lipopolysaccharide
      substantially increased the binding capacity of HIMECs. HIMECs derived from
      inflammatory bowel disease mucosa showed a markedly greater leukocyte-binding
      capacity than normal mucosal HIMECs. Patterns of intercellular adhesion molecule
      1, vascular cell adhesion molecule 1 and E-selectin messenger RNA expression were
      distinct in HIMECs, HUVECs, and mucosal mesenchymal cells. CONCLUSIONS: HIMECs
      represent differentiated endothelial cells with unique functional properties.
      Their dramatically enhanced capacity to bind leukocytes in inflammatory bowel
      disease suggests that HIMECs play an important role in initiating or maintaining
      inflammation.

PMID- 9178683
TI  - Pattern of adhesion molecule expression on vascular endothelium in Helicobacter
      pylori-associated antral gastritis.
AB  - BACKGROUND & AIMS: The inflammatory response in Helicobacter pylori-associated
      gastritis (HAG) is characterized by an intense infiltrate of granulocytes and
      lymphocytes. The emigration of white blood cells into sites of inflammation is
      mediated by receptors on endothelial cells and on blood leukocytes. The aim of
      this study was to characterize endothelial adhesion molecule expression in HAG
      leading to leukocyte infiltration. METHODS: Endothelially expressed adhesion
      molecules were studied in situ by immunohistochemical analysis of antral mucosal
      biopsy specimens from 20 control patients, 10 of whom had chemical gastritis, 10
      normal mucosa, and 44 HAG. Adjacent biopsies were used to evaluate messenger RNA
      (mRNA) transcripts for the respective adhesion molecule and its inducing
      cytokines. RESULTS: Constitutive expression of P-selectin was found in all
      groups. Intercellular adhesion molecule 1 (ICAM-1) was up-regulated in patients
      with HAG and chemical gastritis in contrast to normal controls. Vascular adhesion
      molecule 1 (VCAM-1) was only found within lymphoid aggregates present in HAG.
      Neither mRNA transcripts nor the protein product of E-selectin were detected in
      normal or inflamed mucosa, although mRNA of the E-selectin-inducing cytokines,
      tumor necrosis factor alpha and interleukin 1beta, were found. CONCLUSIONS: Data
      suggest a major role of ICAM-1 and VCAM-1 in leukocyte-endothelial interaction in
      HAG without E-selectin up-regulation showing a unique pattern within the
      gastrointestinal tract, in contrast to observations made in inflammatory bowel
      disease.

PMID- 9178684
TI  - Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: a key
      to increased susceptibility to damage?
AB  - BACKGROUND & AIMS: Portal hypertension predisposes gastric mucosa to increased
      injury. The aim of this study was to determine whether overexpression of
      constitutive nitric oxide synthase (cNOS) is responsible for increased
      susceptibility of portal-hypertensive (PHT) gastric mucosa to damage. METHODS: In
      gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression
      was determined by Northern blotting and cNOS protein expression by Western
      blotting, immunohistochemistry, and enzyme activity assay. Extent of ethanol
      induced gastric mucosal necrosis, mucosal blood flow, and gastric NOS activity in
      PHT and sham-operated rats was determined after administration of N(omega)-nitro
      L-arginine methyl ester (L-NAME) or saline. RESULTS: cNOS messenger RNA level,
      cNOS enzyme activity, and fluorescence signals for cNOS were increased
      significantly in PHT rats compared with controls. Inhibition of overexpressed
      cNOS by L-NAME (5 mg/kg) significantly reduced ethanol-induced mucosal necrosis
      and normalized blood flow in PHT gastric mucosa, whereas this dose of L-NAME
      significantly increased mucosal necrosis in sham-operated rats. CONCLUSIONS:
      Portal hypertension activates the cNOS gene with overexpression of cNOS protein
      in endothelia of gastric mucosal vessels. Excessive NO production by
      overexpressed cNOS may play an important role in the increased susceptibility of
      PHT gastric mucosa to damage.

PMID- 9178685
TI  - Deranged hydrophobic barrier of the rat gastroduodenal mucosa after parenteral
      nonsteroidal anti-inflammatory drugs.
AB  - BACKGROUND & AIMS: Parenteral administration of nonsteroidal anti-inflammatory
      drugs (NSAIDs) may cause gastrointestinal mucosal lesions. The aim of this study
      was to investigate whether parenteral NSAIDs alter surface hydrophobicity of the
      gastroduodenal mucosa. METHODS: Conscious rats received indomethacin or
      diclofenac subcutaneously at different doses (0.5-10 mg/kg). Surface
      hydrophobicity of gastric and duodenal mucosa was determined by contact angle
      measurement at various time points; mucosal prostaglandin synthesis and mucus
      phospholipid content were measured. Also, the effects of NSAIDs were studied in
      bile duct-ligated rats. RESULTS: A single 1-2-mg/kg dose significantly decreased
      hydrophobicity in the stomach and duodenum. The decrease was associated with a
      reduction in mucus phosphatidylcholine. In the duodenum, mucosal prostaglandin
      synthesis was restored 24 hours after NSAID dosing, but hydrophobicity was still
      decreased. There was no adaptation to long-term treatment. In bile duct-ligated
      rats, NSAIDs did not decrease gastric or duodenal hydrophobicity. Moreover, oral
      administration of bile from rats pretreated with parenteral NSAIDs significantly
      decreased mucosal hydrophobicity in untreated rats. CONCLUSIONS: Low-dose NSAIDs
      by parenteral route impair the physicochemical barrier against luminal acidity
      and render the mucosa susceptible to injury. Excretion of NSAIDs in bile seems to
      play a key role in this effect.

PMID- 9178686
TI  - The effect of gastrin-releasing peptide on gastrin and somatostatin messenger
      RNAs in humans infected with Helicobacter pylori.
AB  - BACKGROUND & AIMS: Gastrin-releasing peptide stimulates gastrin secretion but
      also inhibits its release via somatostatin. Exogenous gastrin-releasing peptide
      stimulates a greater increase in plasma gastrin concentrations in patients
      infected with Helicobacter pylori than in uninfected controls. Because this
      infection suppressed gastric mucosal somatostatin, we studied whether the
      increased gastrin response was a result of an abnormal response of the
      somatostatin cell. METHODS: Patients without dyspeptic ulcers received an
      infusion of either gastrin-releasing peptide or saline on separate occasions.
      Acid secretion was measured, and gastric biopsy specimens were taken for gastrin
      and somatostatin messenger RNA (mRNA) analysis and H. pylori diagnosis. RESULTS:
      In response to gastrin-releasing peptide, the increase in plasma gastrin
      concentrations in the infected patients was significantly higher than in the
      uninfected. Antral gastrin mRNA also increased significantly in the infected
      group but decreased significantly in the uninfected group. Basal somatostatin was
      lower in the infected group; gastrin-releasing peptide produced a significant
      increase in antral somatostatin mRNA concentration in infected, but not
      uninfected, patients. CONCLUSIONS: The somatostatin cell responds to gastrin
      releasing peptide in H. pylori infection. Gastrin-releasing peptide normally
      inhibits gastrin mRNA expression, but inhibition is deficient in H. pylori
      infection, possibly because of low stimulated somatostatin levels.

PMID- 9178687
TI  - Distribution of somatostatin receptor messenger RNAs in the rat gastrointestinal
      tract.
AB  - BACKGROUND & AIMS: The gastrointestinal (GI) tract is a major source and target
      of somatostatin (SRIF). Recently, five pharmacologically different SRIF receptors
      (sst1-5) were cloned. The cellular and tissue distribution of the sst1-5
      messenger RNAs (mRNAs) were studied in the rat GI tract using in situ
      hybridization histochemistry (ISHH). METHODS: Two sets of (35)S-uridine
      triphosphate (UTP)-labeled antisense and sense riboprobes were prepared for each
      sst. ISHH was conducted on frozen tissue samples from rat stomach, duodenum,
      jejunum, ileum, colon, and pancreas. RESULTS: mRNAs of all five sst-s are widely
      expressed in the rat GI tract. The distribution pattern for each sst mRNA was
      identical with both antisense probes. No specific signal was found with any of
      the sense probes. Each layer of the different parts of the gut expressed mRNAs of
      multiple sst subtypes. All organs expressed sst3 mRNA very intensely. The lowest
      levels of mRNA expression for all five subtypes within the GI tract were found in
      the pancreas. CONCLUSIONS: The widespread expression of sst mRNAs suggests a
      significant role for SRIF in the regulation of GI function.

PMID- 9178688
TI  - Oxyntomodulin stimulates intestinal glucose uptake in rats.
AB  - BACKGROUND & AIMS: Enteroglucagon peptides have long been proposed as mediators
      of intestinal adaptation, including mucosal growth and nutrient absorptive
      capacity. The hypothesis that infusions of oxyntomodulin, a bioactive form of
      enteroglucagon, would stimulate glucose and amino acid uptake was tested and its
      effects were compared with those of glucagon. METHODS: Rats were infused
      intravenously via minipumps with either saline, rat oxyntomodulin (0.47 nmol x
      kg(-1) x h[-1]), or glucagon (0.88 nmol x kg(-1) x h[-1]) for 7 days, and plasma
      hormone levels were measured. At death, intestinal dimensions and brush border
      uptake of D-glucose and L-proline were measured using an in vitro everted sleeve
      technique. RESULTS: Plasma enteroglucagon and glucagon levels were increased 4-
      and 12-fold, respectively, but there were no effects on food intake, body weight,
      or intestinal dimensions. In contrast, oxyntomodulin and glucagon significantly
      stimulated total intestinal glucose uptake capacity by 44% and 53%, respectively,
      over controls. Oxyntomodulin most potently enhanced glucose uptake in the ileum
      (215%), whereas glucagon's greatest effect was in the jejunum (63%-85%). However,
      neither peptide affected proline uptake. CONCLUSIONS: These results support a
      new, specific action for oxyntomodulin in intestinal adaptation as a glucose
      uptake stimulator and confirm glucagon's role as a regulator of glucose uptake.

PMID- 9178689
TI  - Effects of intestinal stasis on intercellular adhesion molecule 1 expression in
      the rat: role of enteric bacteria.
AB  - BACKGROUND & AIMS: The mechanisms underlying the inflammatory changes associated
      with intestinal stasis are poorly understood. The objective of this study was to
      assess whether endothelial expression of intercellular adhesion molecule 1 (ICAM
      1) and leukocyte recruitment are altered after intestinal stasis. METHODS: ICAM-1
      expression and granulocyte recruitment were quantified in different tissues of
      Sprague-Dawley rats using the double-radiolabeled monoclonal antibody technique
      and peroxidase activity, respectively. RESULTS: Both constitutive and endotoxin
      induced ICAM-1 expression were significantly higher in the cecum than in distal
      colon, a finding that cannot be explained by a difference in endothelial surface
      area between the two organs. Surgical procedures to improve cecal stool flow
      (cecostomy, ileocecostomy) elicited a significant decrease in constitutive ICAM-1
      expression in both cecum and distal colon. Tissue peroxidase activity was
      normally higher in cecum than in distal colon, and this difference was
      significantly reduced by ileocecostomy. Oral administration of antibiotics
      (kanamycin and/or metronidazole for 2 days) significantly reduced constitutive
      ICAM-1 expression in the cecum, but not in the distal colon. CONCLUSIONS: This
      study indicates that intestinal stasis is associated with an increased expression
      of ICAM-1 and granulocyte infiltration, which may be mediated by enteric
      bacteria.

PMID- 9178690
TI  - Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration
      solutions in two models of diarrhea.
AB  - BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L
      sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its
      effectiveness for water and electrolyte absorption in normal rats. The present
      study extends these observations on GA in ORS to two rat models of diarrheal
      disease. METHODS: Juvenile rats were either treated for 1 week with magnesium
      citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or
      luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both
      models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5
      or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium,
      and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with
      GA-supplemented ORS showed an expansion of the basolateral intercellular spaces
      between villus absorptive epithelial cells and the lamina propria, reflecting
      enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0
      g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and
      potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS:
      These experimental studies in models of diarrhea suggest that GA may be a useful
      additive to ORS for the potentiation of water and electrolyte absorption.

PMID- 9178691
TI  - Cytokine modulation of T-lymphocyte activation by intestinal smooth muscle cells.
AB  - BACKGROUND & AIMS: Interleukin 1beta (IL-beta) and tumor necrosis factor alpha
      (TNF-alpha) are present in the neuromuscular layers during intestinal
      inflammation and directly affect intestinal smooth muscle function. We
      investigated whether IL-1beta and TNF-alpha modulate T-cell activation by murine
      intestinal smooth muscle cells (ISMCs). METHODS: alpha- and gamma- actin
      expression in ISMCs was confirmed using reverse-transcription polymerase chain
      reaction (RT-PCR). ISMCs were analyzed for class II major histocompatibility
      complex (MHC), intercellular adhesion molecule 1 (ICAM-1), and B7 before and
      after exposure to interferon gamma (IFN-gamma; 100 or 1000 U/ mL) in the presence
      or absence of IL-1beta (10 ng/mL) or TNF-alpha (5 ng/mL) for 72 hours. T-cell
      proliferation on cytokine-pretreated ISMCs was measured in the absence or
      presence of anti-B7 antibodies. RESULTS: In a dose-dependent fashion, IFN-gamma
      pretreated ISMCs expressed MHC class II, ICAM-1, and B7-2, and stimulated T-cell
      proliferation. Pretreatment of ISMCs with IL-1beta and IFN-gamma reduced MHC
      class II and ICAM-1 expression and inhibited T-cell proliferation. When added
      with 100 U/mL IFN-gamma, TNF-alpha enhanced MHC class II and ICAM-1 expression on
      ISMCs and T-cell proliferation. However, TNF-alpha and 1000 U/mL IFN-gamma
      significantly decreased MHC class II expression and T-cell proliferation. Anti-B7
      2 monoclonal antibody but not anti-B7-1 inhibited T-cell proliferative responses
      by >50%. CONCLUSIONS: Because IL-1beta, TNF-alpha, and T cells are present in the
      intestinal muscle layers during inflammation, these cytokines may serve to
      modulate the activation of T cells in this site.

PMID- 9178692
TI  - Colonic and jejunal motor disturbances after colonic antigen challenge of
      sensitized rat.
AB  - BACKGROUND & AIMS: Inflammation in the colon may alter motility in the proximal
      gut and potentiate clinical symptoms. The aim of this study was to characterize
      the effect of colonic anaphylaxis on local (colonic) and remote (small
      intestinal) motility and identify the mechanism and mediators involved. METHODS:
      Rats were sensitized by intraperitoneal injection of 10 microg egg albumin and
      surgically prepared with electrodes in jejunum and colon and a colostomy tube.
      Colonic and jejunal myoelectric activity were recorded in fasted animals before
      and after colonic antigen challenge without and then after pretreatment with
      specific antagonists. RESULTS: Colonic antigen challenge of sensitized rats was
      associated with significant (1) increase in colonic myoelectric spike activity,
      (2) disruption of fasting jejunal motility and initiation of aborally propagating
      spike complexes, and (3) increase in plasma rat mast cell protease II levels with
      a decrease in granulated mast cells in colon but not jejunum. The myoelectric
      disturbance in both colon and jejunum was inhibited significantly by pretreatment
      with atropine and hexamethonium, doxantrazole, cyclooxygenase, and lipoxygenase
      inhibitors. Methysergide inhibited only the jejunal disturbance. CONCLUSIONS:
      Colonic antigen challenge of sensitized animals results in local mast cell
      activation and the release of mediators that modulate neural pathways to initiate
      both a local colonic and a remote jejunal myoelectric disturbance.

PMID- 9178693
TI  - Electrogastrography can recognize gastric electrical uncoupling in dogs.
AB  - BACKGROUND & AIMS: Electrical uncoupling is the lack of electrical
      synchronization in different parts of the stomach. The ability of
      electrogastrography (EGG) to recognize gastric electrical uncoupling has not been
      adequately studied. The aim of this study was to determine the impact on EGG of
      surgically introduced gastric uncoupling in anesthesized dogs. METHODS: Six pairs
      of bipolar electrodes were inserted into the antral gastric wall of 16
      anesthetized dogs at laparotomy. Eight-channel bipolar cutaneous EGGs were
      simultaneously recorded. Three separate half-hour recordings were made from each
      dog in the basal state and after each of two circumferential cuts of all gastric
      muscle. The stomach was divided into three equally sized areas, each with an
      electrode pair in its anterior and posterior walls. Gastric electrical activity
      was assessed visually. EGG was digitized and processed by computer. RESULTS:
      Criteria for EGG normality were defined from 9 dogs with normal gastric
      electrical activity. After the first antral cut, internal recordings from the
      area below the division were at a lower frequency and often irregular. The second
      cut produced three different frequencies. Suggested criteria for normality
      allowed correct recognition of 93% of all severely abnormal records. Records with
      mild gastric electrical abnormalities were recognized with a sensitivity of 74%.
      CONCLUSIONS: EGG can recognize severe electrical uncoupling.

PMID- 9178694
TI  - The portal pressure response to beta-blockade is greater in cirrhotic patients
      without varices than in those with varices.
AB  - BACKGROUND & AIMS: Nonselective beta-blockers are effective in reducing portal
      pressure in cirrhotic patients. However, this beneficial effect is highly
      variable and may depend on the extent of portal system collateralization. The aim
      of this study was to compare portal pressure response with timolol, a
      nonselective beta-blocker, in cirrhotic patients with and without varices.
      METHODS: Portal and systemic hemodynamics were measured before and after a single
      oral dose of 10 mg of timolol in 50 patients with cirrhosis and portal
      hypertension, 15 with and 35 without esophageal varices. RESULTS: Timolol
      significantly decreased portal pressure in all patients (mean reduction, 20% +/-
      13%; P < 0.0001). The reduction in hepatic venous pressure gradient was greater
      in patients without varices (-24% +/- 14%) than in those with varices (-12% +/-
      8%) (P < 0.01). A decrease in the hepatic venous pressure gradient of <12 mm Hg
      was achieved in 7 of 12 (58%) patients without varices and a baseline pressure
      gradient of <12 mm Hg, but only in 3 of 15 patients with varices (20%) (P <
      0.01). CONCLUSIONS: Timolol is effective in reducing portal pressure in cirrhotic
      patients, more so in patients without varices, suggesting that nonselective beta
      blockers will be more effective in the treatment of portal hypertension when
      administered at early stages, before the development of varices.

PMID- 9178695
TI  - Epitope specificity of Th0/Th2 CD4+ T-lymphocyte clones induced by vaccination
      with rHBsAg vaccine.
AB  - BACKGROUND & AIMS: Different amino acid sequences of hepatitis B virus surface
      antigen (HBsAg) are involved in the activation of CD4+ lymphocytes needed to
      induce an optimal antiviral function. The aim of this study was to characterize
      the CD4-mediated response to immunodominant HBsAg epitopes in hepatitis B virus
      (HBV) vaccine recipients by defining minimal sequences recognized by T cells,
      cytokine profiles, and HLA restriction of peptide recognition. METHODS: T
      lymphocyte lines and clones specific for HBsAg were isolated from the peripheral
      blood of subjects immunized with recombinant HBsAg and stimulated in vitro with
      synthetic peptides spanning the whole HBsAg sequence. RESULTS: Four
      immunodominant epitopes (sequences 21-40, 136-155, 156-175, and 211-226) were
      identified. Using panels of truncated peptides of different length, sequences 21
      28, 165-172, and 215-223 were shown to correspond to the minimal epitopes
      recognized by T cells. The antigen-specific T-lymphocyte proliferation was HLA
      class II restricted, and each peptide could be presented in association with
      different HLA class II determinants. Th0/Th2 cytokine patterns were induced on
      peptide stimulation. CONCLUSIONS: These results indicate the presence of at least
      four immunodominant epitopes within HBsAg that represent potential candidates for
      the design of anti-HBV synthetic vaccines.

PMID- 9178696
TI  - Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis.
AB  - BACKGROUND & AIMS: In a recent study, we suggested that susceptibility to type 1
      autoimmune hepatitis is associated with a six-amino acid motif, LLEQKR, within
      the DR beta polypeptide, but these data are in conflict with contemporary reports
      from Japan and Argentina. The purpose of the present study was to reexamine this
      question in a large independent cohort of patients. METHODS: Eighty-six North
      American white patients and 102 control subjects were studied. HLA class I
      antigens were determined serologically, and the DRB1, DQA1, DQB1, and DPB1 genes
      and the DRB3/4/5 subtypes were determined by high-resolution genotyping. RESULTS:
      The greatest risk was associated with DRB1*0301 (corrected probability [Pc] =
      0.00003; relative risk [RR] = 4.58), and a secondary association with DRB1*0401
      was identified (Pc = 0.000132; RR = 5.97). Protection from disease was associated
      with the DRB5*0101-DRB1*1501 haplotype (Pc = 0.021; RR = 0.3). However, further
      analysis indicated that a lysine residue at position 71 of the DR beta
      polypeptide may be the most important determinant of disease susceptibility (P =
      0.0000003; RR = 8.6, increasing to RR = 16.38 with four lysine residues).
      CONCLUSIONS: DRB1*0301 and DRB1*0401 are confirmed as the principal
      susceptibility alleles for type 1 autoimmune hepatitis, and these data support
      the hypothesis that a lysine residue at position 71 of the DR beta-polypeptide
      chain may be the major risk factor.

PMID- 9178697
TI  - Increased biliary group II phospholipase A2 and altered gallbladder bile in
      patients with multiple cholesterol stones.
AB  - BACKGROUND & AIMS: Multiple cholesterol stones are associated with more biliary
      complications and show more rapid cholesterol nucleation than solitary stones.
      Group II phospholipase A2 (PLA2-II) may play a critical role in the process of
      mucosal inflammation, which in turn may produce pronucleating agents. PLA2-II
      concentrations in gallbladders and gallbladder bile from patients with different
      types of gallstone disease were assayed to correlate PLA2-II with alterations in
      biliary composition. METHODS: PLA2-II protein concentrations were assayed
      immunoradiometrically using monoclonal antibodies against human splenic PLA2-II.
      RESULTS: Immunoreactive PLA2-II levels in gallbladder bile were significantly
      higher in patients with multiple cholesterol stones (68.2 +/- 6.3 ng/dL, mean +/-
      SEM; n = 24) than in those with solitary stones (24.9 +/- 2.8; n = 20; P < 0.01),
      those with multiple pigment stones (24.2 +/- 3.7; n = 18; P < 0.01), or control
      subjects (13.4 +/- 1.7; n = 19; P < 0.01). Increased biliary immunoreactive PLA2
      II levels in multiple cholesterol stones were associated with a concomitant
      increase in the lysophosphatidylcholine to phosphatidylcholine ratio; free
      arachidonate, protein, and hexosamine concentrations; and gallbladder bile
      viscosity. The gallbladders showed an increased PLA2-II protein mass and steady
      state messenger RNA levels, which was associated with increased prostaglandin E2
      levels. CONCLUSIONS: Increased biliary PLA2-II may be of pathogenetic importance
      in multiple cholesterol stones, probably through potentiating gallbladder mucosal
      inflammation with associated biliary alterations favoring cholesterol crystal
      formation.

PMID- 9178698
TI  - Bacterial lipase and high-fat diets in canine exocrine pancreatic insufficiency:
      a new therapy of steatorrhea?
AB  - BACKGROUND & AIMS: Nutrients and properties of lipases affect survival of
      lipolytic activity during aboral gastrointestinal transit. Whether different
      doses and formulations of bacterial lipase and diets affect steatorrhea was
      tested in pancreatic-insufficient dogs. METHODS: A dose of 0-600,000 IU of
      powdered and 135,000 and 300,000 IU of liquid bacterial lipase was given with a
      standard meal to 5 dogs with ligated pancreatic ducts. In 4 dogs, 0 or 300,000 IU
      (normal 6-hour postprandial amount) of powder bacterial lipase was also given
      with five meals containing 850 kcal with different nutrient caloric densities
      (mixture design). Coefficients of fat absorption during 72-hour fecal balance
      studies were used to assess treatments. RESULTS: With the standard meal, powder
      bacterial lipase reduced steatorrhea in a dose-dependent manner (P = 0.03), and
      135,000 and 300,000 IU of the liquid form decreased steatorrhea more than powder
      bacterial lipase (P = 0.017 and 0.057, respectively). Coefficients of fat
      absorption with 300,000 IU of powder bacterial lipase correlated (r2 = 0.79; P <
      0.001) with increasing proportions of fat calories in diets. CONCLUSIONS: Liquid
      bacterial lipase decreases steatorrhea more than powder, and 300,000 IU of powder
      bacterial lipase ingested with high-fat meals corrects canine pancreatic
      steatorrhea. The combination of adequate mixing of small amounts (milligrams) of
      bacterial lipase and high-fat meals abolishes canine steatorrhea and may abolish
      human pancreatic steatorrhea.

PMID- 9178699
TI  - Nitric oxide production by peritoneal macrophages of cirrhotic rats: a host
      response against bacterial peritonitis.
AB  - BACKGROUND & AIMS: Patients and rats with cirrhosis and ascites are prone to
      develop peritonitis. The aim of this study was to assess whether peritoneal
      macrophages of cirrhotic rats without peritoneal infection produce nitric oxide
      and express inducible NO synthase (iNOS). METHODS: NO2- accumulation produced by
      macrophages from control rats and cirrhotic rats with ascites was determined.
      iNOS messenger RNA and protein expression were analyzed by Northern and Western
      blot and immunocytochemical analysis. The in vivo effects of inhibiting iNOS were
      investigated by giving the specific iNOS inhibitor L-N-(1-iminoethyl)-lysine (L
      NIL) or sterile saline to 9 and 7 cirrhotic rats with ascites, respectively.
      RESULTS: Cirrhotic macrophages produced NO2- that was around fourfold greater
      than that of control macrophages after 30 hours in culture. Northern and Western
      blot and immunocytochemical analysis showed the presence of iNOS messenger RNA
      and protein in macrophages of cirrhotic rats. Ascites cultures were positive in
      all rats administered L-NIL and negative in those administered saline.
      CONCLUSIONS: Macrophages of cirrhotic rats produce NO and express iNOS messenger
      RNA and protein, and these changes are not a consequence of overt bacterial
      infection. Because iNOS inhibition results in peritoneal infection, these results
      suggest that iNOS induction in macrophages of cirrhotic rats is a host defense
      response to prevent bacterial peritonitis.

PMID- 9178700
TI  - Altered growth and lack of responsiveness to angiotensin II in aortic vascular
      smooth muscle cells from cirrhotic rats.
AB  - BACKGROUND & AIMS: In cirrhosis, increased amounts of circulating hormones such
      as angiotensin II may induce vascular tone changes and alter vascular smooth
      muscle cell (VSMC) function and growth. The aim of this study was to investigate
      the growth of aortic VSMCs from cirrhotic rats with or without the addition of
      angiotensin II and to determine whether angiotensin II binding was preserved in
      cirrhotic VSMCs. METHODS: Cirrhosis was induced by bile duct ligation. Cell
      growth was studied in cultured aortic VSMCs at passage levels between 4 and 16 by
      determining cell number and protein synthesis. RESULTS: Proliferation rates of
      cirrhotic VSMCs were lower than those of control VSMCs. The addition of
      angiotensin II to control VSMCs caused an increase in cell proliferation and
      protein synthesis. This increase was not observed in cirrhotic cells. There were
      more angiotensin II receptors in cirrhotic than in control VSMCs, but no
      significant changes in affinities were found. Angiotensin II-stimulated protein
      synthesis was dependent on protein kinase C activity and increased intracellular
      Ca2+ concentrations. CONCLUSIONS: This study shows abnormalities in growth
      characteristics and responsiveness to angiotensin II of cultured aortic VSMCs
      from rats with cirrhosis.

PMID- 9178701
TI  - Differential inhibition of epidermal growth factor signaling pathways in rat
      hepatocytes by long-term ethanol treatment.
AB  - BACKGROUND & AIMS: Long-term ethanol intake suppresses liver regeneration in vivo
      and ethanol interferes with epidermal growth factor (EGF)-induced DNA synthesis
      in vitro. Therefore, the effects of long-term ethanol treatment on EGF-activated
      signaling reactions in rat hepatocytes were investigated. METHODS: Hepatocytes
      from long-term ethanol-fed rats and pair-fed controls were stimulated with EGF
      (0.5-20 nmol/L) for 15-120 seconds. Tyrosine phosphorylation of EGF receptor
      (EGFR), Shc, and phospholipase-C gamma1 (PLC gamma), and growth factor receptor
      binding protein 2 (Grb2) coprecipitation with EGFR and Shc were analyzed by
      Western blotting. RESULTS: EGFR autophosphorylation was suppressed at all EGF
      concentrations in ethanol-fed cells compared with pair-fed cells, without
      significant differences in total EGFR protein or EGFR tyrosine kinase activity
      detected in cell lysates, suggesting that intracellular factors suppressed EGFR
      function. EGF-induced PLC gamma tyrosine phosphorylation and inositol 1,4,5
      trisphosphate (InsP3) formation were suppressed, but cytosolic [Ca2+]c elevation
      was little affected, indicating enhanced InsP3-mediated intracellular Ca2+
      release in ethanol-fed cells. Grb2 binding to EGFR was suppressed, but EGF
      induced Shc tyrosine phosphorylation and Grb2 association with Shc were not
      significantly decreased. CONCLUSIONS: Long-term ethanol feeding suppressed EGF
      induced receptor autophosphorylation in rat hepatocytes with differential
      inhibition of downstream signaling processes mediated by PLC gamma, Shc, and
      Grb2. Altered patterns of downstream signals emanating from EGFR may contribute
      to deficient liver regeneration in chronic alcoholism.

PMID- 9178702
TI  - Bile ducts and portal and central veins are major producers of tumor necrosis
      factor alpha in regenerating rat liver.
AB  - BACKGROUND & AIMS: Tumor necrosis factor (TNF) alpha mediates both liver injury
      and regeneration. Kupffer cells are thought to produce TNF because gadolinium
      chloride (GdCl), a drug that depletes Kupffer cells, prevents TNF-mediated
      injury. However, GdCl increases liver TNF and regeneration after partial
      hepatectomy (PH), suggesting that other cells produce TNF during regeneration.
      The aim of this study was to identify the source(s) of TNF after PH in normal and
      Kupffer cell-depleted rats. METHODS: Livers were harvested at 0, 1, or 48 hours
      after PH from saline- or GdCl-treated rats. TNF expression was evaluated by in
      situ reverse-transcription polymerase chain reaction and immunohistochemistry.
      RESULTS: In saline-treated rats, neither TNF transcripts nor protein was detected
      before PH, but both increased after PH. One hour after PH, 64% +/- 8% portal
      areas had TNF-positive bile ducts or veins and 61% +/- 1% central veins were TNF
      positive; by 48 hours, 57% +/- 1% portal areas, 40% +/- 1% central veins, and a
      few sinsusoidal cells expressed TNF. In GdCl-treated rats, TNF was expressed in
      22% +/- 6% portal areas before PH; in 76% +/- 3% portal areas and 75% central
      veins at 1 hour; and in 88% +/- 2% portal areas and 80% +/- 9% central veins at
      48 hours after PH. CONCLUSIONS: In the regenerating livers of both normal and
      Kupffer cell-depleted rats, bile ducts and veins are the predominant sources of
      TNF-alpha.

PMID- 9178703
TI  - Kernicterus in an adult who is heterozygous for Crigler-Najjar syndrome and
      homozygous for Gilbert-type genetic defect.
AB  - Gilbert syndrome is a common genetic disorder associated with mild unconjugated
      hyperbilirubinemia and no clinical illness. In contrast, Crigler-Najjar syndrome
      types I and II are rare genetic disorders associated with severe unconjugated
      hyperbilirubinemia and a life-long risk of kernicterus. Patients with Gilbert
      syndrome have low levels of a normal form of uridinediphosphoglucuronate
      glucuronosyltransferase because of a defect in the promoter region of both
      alleles, whereas patients with Crigler-Najjar syndrome are homozygous for a
      defect that yields an abnormal form of the enzyme that has limited or no
      activity. This case report describes a young adult with Crigler-Najjar syndrome
      type II in whom kernicterus developed after a laparoscopic cholecystectomy. The
      development of kernicterus was the result of a largely preventable series of
      events that lead to an increase in the free fraction of his serum bilirubin.
      Analysis of his genetic defect showed that he was homozygous for the mutation
      associated with Gilbert syndrome and heterozygous for a second mutation in the
      open reading frame of one allele of the bilirubin uridinediphosphoglucuronate
      glucuronosyltransferase gene. The combined defect leads to severe
      hyperbilirubinemia and shows how seemingly benign genetic defects, when combined,
      can cause serious clinical disease.

PMID- 9178704
TI  - Association between pancreatic cystadenocarcinoma, malignant liver cysts, and
      polycystic disease of the kidney.
AB  - Polycystic kidney disease is an autosomal dominant disease that may be associated
      with cystic disease of the liver. In women, the cysts may develop early and be
      more troublesome than in men. Cystadenocarcinoma of the pancreas is uncommon,
      comprising 1% of primary pancreatic malignancies. This case report is the first
      to describe a familial association between polycystic kidney disease and
      cystadenocarcinoma of the pancreas and liver in the English medical literature. A
      patient with autosomal dominant polycystic kidney disease (ADPKD) and multiple
      hepatic cysts developed cystadenocarcinoma of the pancreas with multiple
      malignant liver cysts. The patient's mother, sister, and niece had ADPKD, and the
      patient's sister also died of pancreatic cystadenocarcinoma. We believe that the
      development of these two disease entities in which the primary pathology is cyst
      formation has a genetic association.

PMID- 9178705
TI  - Are there three types of Helicobacter pylori gastritis?

PMID- 9178706
TI  - American Gastroenterological Association. A century of regulatory peptides: from
      discovery to function.

PMID- 9178707
TI  - Presentation of the William Beaumont Prize to Bert Vogelstein, M.D.

PMID- 9178708
TI  - American Gastroenterological Association medical position statement: irritable
      bowel syndrome.

PMID- 9178709
TI  - Irritable bowel syndrome: a technical review for practice guideline development.

PMID- 9178710
TI  - Barrett's esophagus: should we brush off this ballooning problem?

PMID- 9178711
TI  - High-dose famotidine for prevention of NSAID ulcers?

PMID- 9178712
TI  - Persistence of diarrhea in treated celiac sprue: refractory disease or another
      organ's malfunction?

PMID- 9178713
TI  - Physician specialty and cost-effectiveness of diverticulitis care: a difficult
      knot to untangle.

PMID- 9178714
TI  - Screening in cyberspace: the next generation?

PMID- 9178715
TI  - Designer drugs for inflammatory bowel disease.

PMID- 9178716
TI  - Maintaining remissions in Crohn's disease: a fat chance to please.

PMID- 9178717
TI  - Eradication of high-grade dysplasia using 5-ALA and acid suppression: a
      (photo)dynamic duo.

PMID- 9178718
TI  - IBD-associated bone loss: is inflammation the explanation?

PMID- 9178719
TI  - Need for screening colonoscopy in first-degree relatives.

PMID- 9178720
TI  - Hyperammonemia after heart-lung transplantation.

PMID- 9178721
TI  - Gastric permeability in celiac disease.

PMID- 9178722
TI  - Aging, immunity, and cardiopulmonary bypass surgery: adding insult to injury.

PMID- 9178723
TI  - Nitric oxide binding and the adverse effects of cell-free hemoglobins: what makes
      us different from earthworms.

PMID- 9178724
TI  - Pathophysiology of CML: do defects in integrin function contribute to the
      premature circulation and massive expansion of the BCR/ABL positive clone?
AB  - Hematopoiesis takes place in close contact with the marrow microenvironment.
      Normal progenitors adhere through a variety of receptors to stroma and
      extracellular matrix components, including fibronectin. Adhesion through beta1
      integrin receptors to fibronectin not only anchor progenitors to the stroma but
      also result in direct adhesion-mediated signaling that inhibits progenitor
      proliferation. In contrast to normal hematopoiesis, chronic myelogenous leukemia
      (CML) is characterized not only by abnormal, premature circulation of primitive
      progenitors in the blood but also by continuous progenitor proliferation.
      Although CML progenitors express the same integrin receptors as normal
      progenitors, they fail to adhere to stroma and fibronectin, suggesting structural
      or functional abnormalities of these receptors. Furthermore, CML cells present in
      contact with stroma or fibronectin continue to proliferate, suggesting that
      failure to adhere through integrin receptors may also underlie the abnormal
      proliferation of CML progenitors. The observation that integrin-mediated adhesion
      and proliferation-inhibitory signaling can be restored through treatment with
      interferon-alpha or an activating anti-beta1-integrin antibody suggests a
      functional rather than structural defect that may be related to the presence of
      the BCR/ABL gene rearrangement in these cells. Insights into the role of
      integrins as adhesion molecules but also receptors that instruct hematopoietic
      progenitors to survive, proliferate, and possibly differentiate will not only
      further our understanding of the normal hematopoietic process but also provide
      insights into diseases characterized by deranged adhesion and proliferation that
      may lead to novel therapeutic approaches.

PMID- 9178725
TI  - Lymphocyte and monocyte subset changes during cardiopulmonary bypass: effects of
      aging and gender.
AB  - Complications of cardiopulmonary bypass (CPB) may be associated with either
      immune suppression or immune activation, but the specific effects of CPB on many
      lymphocyte and monocyte subsets are unclear. In addition, the increasing age of
      patients undergoing cardiac surgery raises the possibility of even greater
      effects on the immune system in elderly patients. We measured immunophenotypic
      alterations of circulating lymphocytes and monocytes after CPB in male and female
      cardiac surgery patients who were either younger than 60 or older than 75 years
      of age. The total lymphocyte counts in all patients decreased postoperatively;
      older patients had significantly lower counts at all time points. The absolute
      decline was greatest among T cells and particularly CD4+ T cells, which reached
      an average nadir of 251 cells/microl on postoperative day 1 in the older
      patients. The percentages of CD8+, CD4+CD45RA+, and CD4+CD45RO+ T cells did not
      change significantly, whereas the percentages of B cells and natural killer cells
      increased. Both T and B lymphocytes and monocytes showed evidence of activation,
      with increased percentages of CD3+HLADr+, CD3+IL2R+, and CD19+CD23+ lymphocytes
      and increased expression of CD11b on monocytes. By contrast, expression of class
      II major histocompatibility antigen (HLADr) monocytes decreased significantly. We
      conclude that CPB produces a profound alteration in the pool of circulating
      lymphocytes and monocytes, evidenced by decreased numbers of lymphocyte subsets
      including CD4+ cells and decreased expression of monocyte surface membrane
      proteins important for antigen presentation; CPB also activates a variety of
      specific circulating mononuclear cell subsets. Older patients showed patterns of
      lymphocyte and monocyte activation comparable to those of younger patients;
      however, they had consistently lower lymphocyte numbers and a trend toward
      decreased monocyte HLADr expression, potentially placing them at greater risk for
      infectious complications. Gender had no effect.

PMID- 9178726
TI  - Effects of polymerization on the hypertensive action of diaspirin cross-linked
      hemoglobin in rats.
AB  - It is believed that the hypertensive effect of diaspirin crosslinked hemoglobin,
      a viable blood substitute, can be resolved by polymerization, which reduces the
      diffusion of this derivative into the interstitial space between nitric oxide
      producing endothelium and the target vascular smooth muscle. We studied the
      systemic and renal responses to infusion of three cell-free human hemoglobins in
      anesthetized isovolemic rats: unmodified (HbA0), crosslinked (alpha-DBBF), and
      polymerized crosslinked (poly alpha-DBBF). HbA0 produced a significant increase
      in mean arterial blood pressure (MAP) throughout the 60-minute infusion. alpha
      DBBF, on the other hand, produced a more marked and prolonged increase in MAP
      over 120 minutes. Only a moderate increase in MAP was observed in rats after a 30
      minute infusion with poly alpha-DBBF. The extent of renal insufficiency produced
      by these proteins, as determined by the glomerular filtration rate, was in the
      following order: HbA0 > poly alpha-DBBF > alpha-DBBF. Infusion of poly alpha
      DBBF, under hypovolemic but not isovolemic conditions in rats, produced an
      increase in heart rate, cardiac output, and stroke volume and a decrease in total
      peripheral resistance after 60 minutes. Chemical polymerization to increase the
      size of alpha-DBBF does not appear to improve its hemodynamic properties in rats,
      especially under partial exchange transfusion, a more clinically relevant
      indication for a hemoglobin-based blood substitute.

PMID- 9178727
TI  - Thrombin induces thrombomodulin mRNA expression via the proteolytically activated
      thrombin receptor in cultured bovine smooth muscle cells.
AB  - Thrombin, an important mitogen governing smooth muscle cell proliferation, binds
      to cultured bovine aortic smooth muscle cells (BASMCs) via both the
      proteolytically activated thrombin receptor (PATR) and thrombomodulin (TM).
      Although TM mRNA expression and functional activity is regulated by thrombin in
      human endothelial cells and mouse hemangioma cells, it remains unclear in those
      models whether the increased TM mRNA expression observed upon thrombin
      stimulation is mediated through the activation of PATR or via TM occupancy. We
      observed in cultured BASMCs that TM mRNA is increased threefold to sixfold by
      either thrombin, basic fibroblast growth factor (bFGF), or platelet-derived
      growth factor (PDGF). The increase in TM mRNA with thrombin is time dependent
      (maximal at 3 hours), a consequence of increased mRNA stability, and accompanied
      by increases in cell surface TM functional activity. Thrombin-induced TM mRNA was
      reproduced by the hexameric thrombin receptor-activating peptide (TRAP6) and
      augmented by a TM-specific antibody. Together, these data suggest that up
      regulation of TM mRNA by thrombin is mediated via the PATR. We speculate that
      increases in BASMC TM mRNA and activity after thrombin may contribute to the
      impaired thrombus formation observed after atherosclerotic vascular injury.

PMID- 9178729
TI  - Binding of acetaldehyde to rat gastric mucosa during ethanol oxidation.
AB  - Acetaldehyde, the first product of ethanol metabolism, has previously been shown
      to form potentially harmful adducts with various proteins. The aim of this study
      was to investigate whether acetaldehyde--either exogenous or metabolically
      derived--binds to gastric mucosal proteins. Homogenized rat gastric mucosa was
      incubated with various concentrations of radiolabeled acetaldehyde or ethanol for
      different time periods. Acetaldehyde-protein adducts were determined by a liquid
      scintillation counter. In addition, mucosa was incubated with nonlabeled ethanol,
      and the acetaldehyde formed was measured by using headspace gas chromatography.
      Incubation of gastric mucosa with (14C)-acetaldehyde led to a concentration- and
      time-dependent radiolabeling of mucosal proteins. Formation of acetaldehyde
      adducts occurred relatively rapidly within 30 minutes and even at low
      acetaldehyde levels (5 micromol/L). Stable adducts represented 77% +/- 5% (mean
      +/- SEM) of the total adducts formed. In the presence of ethanol, acetaldehyde
      production and adduct formation took place in a concentration- and time-dependent
      manner. 4-Methylpyrazole and sodium azide inhibited acetaldehyde production to 7%
      +/- 1% of control and decreased the amount of acetaldehyde adducts to 55% +/- 8%.
      Enhanced acetaldehyde formation (to 420% +/- 50%) was clearly reflected in
      increased adduct formation (550% +/- 110%). In conclusion, both exogenous and
      endogenous acetaldehyde binds to gastric mucosal proteins in vitro. Gastric
      mucosal acetaldehyde production and the consequent adduct formation could be a
      pathogenetic factor behind ethanol-associated gastric injury.

PMID- 9178730
TI  - Phagocytosis and burst activity of granulocytes and monocytes after stem cell
      transplantation.
AB  - In addition to a low number of leukocytes, an impairment of leukocyte function
      can also contribute to the increased susceptibility to bacterial and fungal
      infection in marrow transplant recipients. Phagocytosis and oxidative burst
      activity were measured in patients at various stages after transplant by using
      assay systems that are based on the quantification of the immunofluorescence of
      ingested bacteria. Although phagocytosis was normal in most transplant recipents,
      the oxidative burst of granulocytes was significantly impaired in recipients
      early after autologous and allogeneic transplants. Patients who underwent tests
      in later stages after transplant had normal leukocyte function test results.
      These observations are compatible with the notion that recipients early after
      bone marrow transplant may be able to phagocytize bacteria readily but that their
      ability to inactivate them via the oxidative burst might be compromised.

PMID- 9178728
TI  - Novel role of prostacyclin in stress-induced gastric mucosal lesion formation in
      rats.
AB  - We investigated the novel role of prostacyclin (PGI2) in gastric mucosal lesion
      formation induced by stress in rats. Gastric 6-keto-prostaglandin F1alpha (6-keto
      PGF1alpha) levels were significantly increased 30 minutes after water-immersion
      restraint stress (WIR). Subcutaneous indomethacin (IM) (5 mg/kg) inhibited this
      increase but significantly exacerbated gastric mucosal lesion formation in rats
      subjected to WIR. Although gastric myeloperoxidase (MPO) activity was not
      increased by WIR, it significantly increased with time after WIR in animals
      pretreated with IM. NS-398, a selective inhibitor of cyclooxygenase-2, did not
      inhibit the WIR-induced increase in gastric 6-keto-PGF1alpha. Neither the gastric
      lesion index nor gastric MPO activity were affected in animals pretreated with NS
      398 and subjected to WIR. WIR-induced mucosal lesion formation was significantly
      inhibited in animals given iloprost, a stable analog of PGI2, and in those with
      nitrogen mustard-induced leukocytopenia. Iloprost prevented the gastric leukocyte
      accumulation and exacerbation of gastric mucosal lesions induced by IM in animals
      subjected to WIR. These IM-induced events also were prevented in animals
      subjected to WIR with nitrogen mustard-induced leukocytopenia. These observations
      implicate leukocytes in the process leading to gastric mucosal lesions induced by
      WIR. The increase in WIR-induced gastric PGI2 synthesis, mainly mediated by
      cyclooxygenase-1, appears important in preventing lesion formation, not only by
      maintaining gastric mucosal blood flow but also by inhibiting leukocyte
      activation.

PMID- 9178731
TI  - Time-dependent expression of cytochrome P450 genes in primary cultures of well
      differentiated human hepatocytes.
AB  - We sought to establish an in vitro system to study the regulation of highly
      differentiated hepatocellular functions, and specifically the time-dependent
      expression of four cytochrome P450 (P450) genes at the messenger RNA (mRNA) and
      protein levels. When seeded onto matrigel, hepatocytes could be maintained for 8
      days in media that were free of serum and hormones (except for insulin). Cells
      retained a spherical phenotype; they secreted albumin and not alpha-fetoprotein;
      and the cellular RNA/DNA ratio rose progressively in culture. The isolation
      procedure and the duration of culture affected expression of specific P450s
      differently. CYP1A2, CYP2C9, and CYP2E1 mRNAs were not altered by cell isolation,
      and levels of CYP1A2 and CYP2C9 mRNA were also maintained for 8 days in culture,
      whereas CYP2E1 mRNA declined to 9% of values in fresh hepatocytes by day 8.
      CYP3A4 mRNA content was considerably decreased in freshly isolated hepatocytes
      compared with normal liver, and expression of this gene during the course of
      culture was more variable than that of the other P450s. Use of Williams' E medium
      considerably enhanced accumulation of CYP3A4 mRNA, compared with modified
      Waymouth 752/1 medium, but had a detrimental effect on levels of the other P450
      mRNAs. Despite high levels of expression at the mRNA level, the microsomal
      protein contents of CYP1A2, CYP2C9, CYP2E1, and CYP3A4 declined progressively
      during the course of culture; this decline was most rapid for CYP3A4. These
      results confirm the potential of primary cultures of well-differentiated human
      hepatocytes for studies of P450 gene regulation in humans, but they also
      demonstrate that culture conditions are variables that must be carefully
      controlled when examining liver-specific gene expression in vitro. In particular,
      time in culture may variably affect expression of P450 enzyme changes at both the
      mRNA and protein levels.

PMID- 9178732
TI  - Treatment of Wilson's disease with zinc: XIV. Studies of the effect of zinc on
      lymphocyte function.
AB  - Although administration of zinc to human subjects has been reported to interfere
      with lymphocyte function, this single report has never been confirmed or refuted.
      We have developed zinc as a lifelong therapy for patients with Wilson's disease.
      Interference with lymphocyte function occurring as a side effect of zinc therapy
      could produce serious problems in our patients. We evaluated lymphocyte mitogenic
      response and natural killer cell activity in patients with Wilson's disease
      treated for 5 years or longer with zinc, in comparison with normal controls, and
      found no differences. In a second study, we evaluated these same parameters in
      patients with Wilson's disease before and after 1 year of zinc therapy, and again
      found no significant differences. We have seen no indications of immune
      suppression or increased susceptibility to infections in our patients, who have
      now been treated with zinc for up to 15 years. We conclude that any side effects
      from compromised lymphocyte function caused by administration of zinc are not of
      concern to patients with Wilson's disease.

PMID- 9178733
TI  - Self-association of bound fibrinogen on platelet surfaces.

PMID- 9178734
TI  - Nontoxic embolic liquids for treatment of arteriovenous malformations.
AB  - Interventional radiology is becoming one of the standard treatments of
      arteriovenous malformation (AVM). Cyanoacrylate derivatives and polymer solutions
      are widely used to occlude the AVM nidus by their injection through a catheter,
      but they are far from satisfactory embolic liquids. For instance, cyanoacrylate
      derivatives sometimes glue the catheter to the artery, resulting in serious
      complications; in addition, the organic solvents used to dissolve polymers cause
      damage to the surrounding brain tissue of the AVM. Therefore, we attempted to
      develop embolic liquids by dissolving poly(2-hydroxyethyl methacrylate-co-methyl
      methacrylate) in Iopamiron with an addition of a small amount of ethyl alcohol.
      This new embolic liquid is not cytotoxic and is easily injected into the AVM
      through a thin, long catheter to effectively occlude the AVM.

PMID- 9178735
TI  - Assessment of urinary tract biomaterial encrustation using a modified Robbins
      device continuous flow model.
AB  - Encrustation of biomaterials employed in the urinary tract remains a major
      problem resulting in obstruction or blockage of catheters and stents. Therefore,
      resistance to encrustation is a desirable feature of biomaterials employed in
      such devices. The novel assessment of biomaterial encrustation employing a
      continuous flow model based on a modified Robbins device is described. Artificial
      urine was used in conjunction with 5% CO2 to simulate the physiological
      environment within the upper urinary tract. The widely used urinary device
      biomaterials, silicone and polyurethane, were investigated in the model for
      hydroxyapatite and struvite encrustation. Scanning electron microscopy, energy
      dispersive X-ray analysis, and atomic absorption spectroscopy all showed that
      silicone was less prone to encrustation than polyurethane and that hydroxyapatite
      deposition was predominant on both surfaces. The model has the advantage that a
      large number of biomaterials may be investigated simultaneously because several
      Robbins devices may be placed in parallel. The model is recommended for
      comparative evaluation of biomaterial candidates for use in urinary tract
      devices.

PMID- 9178736
TI  - Canine chondrocytes seeded in type I and type II collagen implants investigated
      in vitro.
AB  - Synthetic and natural absorbable polymers have been used as vehicles for
      implantation of cells into cartilage defects to promote regeneration of the
      articular joint surface. Implants should provide a pore structure that allows
      cell adhesion and growth, and not provoke inflammation or toxicity when implanted
      in vivo. The scaffold should be absorbable and the degradation should match the
      rate of tissue regeneration. To facilitate cartilage repair the chemical
      structure and pore architecture of the matrix should allow the seeded cells to
      maintain the chondrocytic phenotype, characterized by synthesis of cartilage
      specific proteins. We investigated the behavior of canine chondrocytes in two
      spongelike matrices in vitro: a collagen-glycosaminoglycan (GAG) copolymer
      produced from bovine hide consisting of type I collagen and a porous scaffold
      made of type II collagen by extraction of porcine cartilage. Canine chondrocytes
      were seeded on both types of matrices and cultured for 3 h, 7 days, and 14 days.
      The histology of chondrocyte-seeded implants showed a significantly higher
      percentage of cells with spherical morphology, consistent with chondrocytic
      morphology, in the type II sponge at each time point. Pericellular matrix stained
      for proteoglycans and for type II collagen after 14 days. Biochemical analysis of
      the cell seeded sponges for GAG and DNA content showed increases with time. At
      day 14 there was a significantly higher amount of DNA and GAG in the type II
      matrix. This is the first study that directly compares the behavior of
      chondrocytes in type I and type II collagen matrices. The type II matrix may be
      of value as a vehicle for chondrocyte implantation on the basis of the higher
      percentage of chondrocytes retaining spherical morphology and greater
      biosynthetic activity that was reflected in the greater increase of GAG content.

PMID- 9178737
TI  - Technique to control pH in vicinity of biodegrading PLA-PGA implants.
AB  - This in vitro study was performed to examine if the pH decrease in the vicinity
      of degrading polylactic acid (PLA) and polyglycolic acid (PGA) polymers can be
      offset by incorporation of basic salts within PLA-PGA implants. It has been
      suggested that such pH lowering results in adverse effects, which may be
      responsible for biocompatibility concerns raised recently about PLA and PGA
      polymers. The results indicated that all three salts investigated in this study
      were successful in controlling the decrease in pH due to the acidic degradation
      products of the copolymer. The pH of the test media for the control group fell to
      a value of 3.0 at 9 weeks. Implants containing calcium carbonate maintained the
      pH value between 7.4 and 6.3 throughout the degradation process. Implants with
      calcium hydroxyapatite and sodium bicarbonate controlled the pH values between
      6.9 and 4.3 and 8.2 and 4.5, respectively. At 3 weeks, marked swelling of
      implants containing calcium carbonate or sodium bicarbonate was observed relative
      to the control implants. The molecular weight and mass changes in the implants
      did not show any significant differences at 9 weeks. Thus, results from this in
      vitro model show that a significant decrease in pH in the vicinity of PLA-PGA
      implants can be avoided by incorporating basic salts.

PMID- 9178738
TI  - Autosterilization of biodegradable implants by injection molding process.
AB  - Sterilization of degradable implants by standard procedures may damage the parts
      due to the labile chemical nature of the polymers. This study examined whether
      the injection molding process used for the production of polymeric parts may
      itself sterilize the implant due to high temperature, pressure, and shear forces
      applied. Poly-D,L-lactic acid (PDLLA) and poly-L-lactic acid (PLLA) granules were
      contaminated with thermoresistant spores of Bacillus stearothermophilus (>10(5)
      spores/g). Sterile and contaminated granules of both polymers were injection
      molded and tested for sterility. All 27 samples produced with sterile PDLLA and
      processed at 120 degrees C and all 18 samples produced with sterile PLLA at 200
      degrees C remained sterile after injection molding and handling. However, in five
      out of 28 PDLLA samples and in one out of 26 PLLA samples produced with
      contaminated material, spores had survived the process. In conclusion, the
      injection molding process could not reliably sterilize parts produced with
      polylactic acid granules that were heavily contaminated with thermoresistant
      organisms. However, the number of viable spores was significantly reduced by more
      than 99.99%. Thus, the injection molding process might allow the
      autosterilization of parts produced with raw material that is not heavily
      contaminated.

PMID- 9178739
TI  - Bonding strength of bonelike apatite layer to Ti metal substrate.
AB  - Our previous study showed that titanium metal forms a bonelike apatite layer on
      its surface in simulated body fluid when it was subjected to NaOH and heat
      treatments to form a sodium titanate hydrogel or amorphous sodium titanate
      surface layer. In the present study, bonding strength of the apatite layer formed
      on the titanium metals to the substrates were examined under tensile stress, in
      comparison with those of the apatite layers formed on Bioglass 45S5-type glass,
      dense sintered hydroxyapatite, and glass-ceramic A-W, which are already
      clinically used. The NaOH-treated titanium metals showed higher bonding strength
      of the apatite layer to the substrates, which was maximized by heat treatments at
      500 and 600 degrees C, than all the examined bioactive ceramics. It is believed
      that bioactive metals thus obtained are useful as bone substitutes, even under
      load-bearing conditions.

PMID- 9178740
TI  - Blast coating method: new method of coating titanium surface with hydroxyapatite
      at room temperature.
AB  - When a titanium plate was blasted with hydroxyapatite [HAP;
      Ca10[x](HPO4)[x](PO4)[6-x](OH)[2-x]] powder at room temperature using an ordinary
      sandblaster, the surface of the titanium plate was found to be coated with HAP
      homogeneously and completely. The coated layer was examined with energy
      dispersive X-ray spectroscopy and X-ray diffraction and was found to be the same
      as the HAP powder used with respect to composition and crystallographic
      structure. The coated HAP layer was tightly attached to the surface of the
      titanium plate, at least at the level of scanning electron microscopy.
      Interestingly, the HAP particles stuck together at room temperature as if they
      were sintered. The coating was stable against ultrasonication in water for at
      least 5 min, and it was difficult to remove by nail scratching. Thus, the bonding
      strength between the HAP powder and the titanium plate was much higher than that
      achieved with currently employed room temperature coating processes such as
      dipping, electrophoretic deposition, and electrochemical deposition. Therefore,
      the blast coating method is potentially valuable for the fabrication of useful
      biomaterials for hard tissue replacement.

PMID- 9178741
TI  - Integrated system for preparation of bone cement and effects on cement quality
      and environment.
AB  - We developed a prepacked mixing system for the preparation of bone cement. The
      system is based on mixing and collection of bone cement under a vacuum and serves
      as both the storage and mixing device for the cement components, thereby
      minimizing the exposure of the operating staff to the monomer and the risk for
      contamination of the cement during preparation. We evaluated the system using
      Palacos R and Simplex P. The cement produced was compared with cement obtained
      from a commercially available mixing system. Temperature evolution during curing,
      handling characteristics, density, and porosity of the cement obtained were
      analyzed. The results showed that the experimental system produces cement with
      physical properties (i.e., setting times and temperature, porosity, and density)
      equal to or better than those obtained with commercially available systems.
      Reducing the amount of monomer in the experimental system led to a reduction of
      the curing temperature without compromising the physical properties of the
      cements.

PMID- 9178743
TI  - Properties of acrylic bone cement: state of the art review.
AB  - Acrylic bone cement occupies a distinctive place in the hierarchy of synthetic
      biomaterials, because it is the only material currently used for anchoring the
      prosthesis to the contiguous bone in a cemented arthroplasty. However, the cement
      is not without its drawbacks. The main one is the role that it has been
      postulated to play in the aseptic loosening and, hence, clinical life of the
      arthroplasty. In turn, this role is directly related to the mechanical properties
      of the cement, especially the resistance to fracture of the cement in the mantle
      at the cement-prosthesis interface or the cement-bone interface. The present work
      is a detailed critical review of the recent literature on the properties of bone
      cement that are considered germane to its use in the stated application. The
      relevant properties are identified and a case is made for including each of them.
      Compilations of the values of these properties, obtained under clearly identified
      conditions, are presented for the six commercial formulations of bone cement in
      current popular orthopedic use. The gaps and unresolved questions in the current
      data base, efforts that should be made to address these issues, and research
      directions are covered.

PMID- 9178742
TI  - Mechanical properties of acrylic bone cement containing PMMA-SiO2 hybrid sol-gel
      material.
AB  - An organic-inorganic hybrid material, poly(methyl methacrylate) (PMMA)-SiO2 (SiO2
      content of 72 wt%), was prepared by incorporating PMMA structure units covalently
      into an SiO2 glass network via the sol-gel approach. The hybrid sol-gel material
      PMMA-SiO2 was subsequently used as the solid powder component of bone cement and
      its mechanical properties were evaluated. The effects of the addition of
      tricalcium phosphate (TCP), hydroxyethyl methacrylate (HEMA), and ethylene glycol
      dimethacrylate (EGDMA) on the properties of the sol-gel hybrid bone cement were
      also investigated. The influence of these components on the temperature rise
      during polymerization was discussed. It was found that the new bone cement
      containing PMMA-SiO2 hybrid sol-gel material had higher modulus than that of
      Simplex-P bone cement. The addition of TCP in the new bone cement increased the
      Young's modulus and the polymerization time; the inverse was observed for the
      tensile, bending, and compressive strengths, and the polymerization temperature.
      The addition of HEMA and EGDMA in the new bone cement had the opposite effect of
      TCP. The comparison between the new sol-gel bone cement and the commercial
      Simplex P bone cement was discussed.

PMID- 9178744
TI  - Characterization of an intronic promoter of a cyclic adenosine 3',5'
      monophosphate (cAMP)-specific phosphodiesterase gene that confers hormone and
      cAMP inducibility.
AB  - In the Sertoli cell, FSH stimulates transcription of a cAMP-phosphodiesterase
      (PDE) gene (PDE4D) and accumulation of corresponding mRNA and PDE protein. The
      regulation of this PDE gene is an important component of the desensitization
      state induced by this hormone. Given the ubiquitous nature of this regulation
      controlling cAMP levels, the molecular basis for the PDE4D induction was further
      investigated. FSH stimulation of the Sertoli cell causes the accumulation of only
      two of the four known PDE4D mRNAs (PDE4D1 and PDE4D2). The promoter controlling
      the expression of these two messages was identified and characterized. An EcoRI
      fragment containing a coding exon as well as 5'-upstream sequence of the PDE4D1/2
      mRNA was isolated from rat genomic libraries and sequenced. No TATA box was
      identified, but GC-rich regions were present upstream of the putative translation
      start site. RNAse protection and PCR analysis indicated the presence of at least
      two distinct cap sites. This genomic region had promoter activity when
      transfected both in Sertoli and MA-10 cells. Deletion mutation indicated that
      basal promoter activity was contributed by regions upstream of both cap sites.
      Transcription from this promoter was activated by FSH and (Bu)2cAMP, and elements
      responsible for cAMP regulation were present upstream from the second cap site.
      These data demonstrate that an intronic promoter that is cAMP- and hormone
      inducible directs the expression of these truncated PDE proteins.

PMID- 9178745
TI  - Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling
      pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the
      two loci for Jansen's metaphyseal chondrodysplasia.
AB  - Two different activating PTH/PTH-related peptide (PTHrP) receptor mutations,
      H223R and T410P, were recently identified as the most likely cause of Jansen's
      metaphyseal chondrodysplasia. To assess the functional importance of either amino
      acid position in the human PTH/PTHrP receptor, H223 and T410 were individually
      replaced by all other amino acids. At position 223, only arginine and lysine led
      to agonist-independent cAMP accumulation; all other amino acid substitutions
      resulted in receptor mutants that lacked constitutive activity or were
      uninformative due to poor cell surface expression. In contrast, most amino acid
      substitutions at position 410 conferred constitutive cAMP accumulation and
      affected PTH/PTHrP receptor expression not at all or only mildly. Mutations
      corresponding to the H223R or T410P exchange in the human PTH/PTHrP receptor also
      led to constitutive activity when introduced into the opossum receptor homolog,
      but showed little or no change in basal cAMP accumulation when introduced into
      the rat PTH/PTHrP receptor. The PTH/PTHrP receptor residues mutated in Jansen's
      disease are conserved in all mammalian members of this family of G protein
      coupled receptors. However, when the equivalent of either the H223R or the T410P
      mutation was introduced into several other related receptors, including the PTH2
      receptor and the receptors for calcitonin, secretin, GH-releasing hormone,
      glucagon-like peptide I, and CRH, the resulting mutants failed to induce
      constitutive activity. These studies suggest that two residues in the human
      PTH/PTHrP receptor, 223 and 410, have critical roles in signal transduction, but
      with different sequence constrains.

PMID- 9178746
TI  - Somatostatin acts by inhibiting the cyclic 3',5'-adenosine monophosphate
      (cAMP)/protein kinase A pathway, cAMP response element-binding protein (CREB)
      phosphorylation, and CREB transcription potency.
AB  - Somatostatin (SRIF) was discovered as an inhibitor of GH secretion from pituitary
      somatotroph cells. SRIF analogs are very effective agents used to treat
      neuroendocrine tumors and are now being used with increasing frequency in
      clinical trials to treat more aggressive malignancies. However, the cellular
      components mediating SRIF signal transduction remain largely unknown. We have
      stably overexpressed the SRIF type 2 receptor (SST2) in GH4 rat somatomammotroph
      cells, establishing a physiologically relevant model system. In this model, the
      SRIF analog, BIM23014, inhibited forskolin-induced cAMP accumulation, protein
      kinase A activation, cAMP response element-binding protein phosphorylation, and
      Pit-1/GHF-1 promoter activation in an okadaic acid-insensitive manner. Pertussis
      toxin inhibited the effects of BIM23014, documenting that SST2 signaling was
      coupled to Gi. Moreover, the inhibitory effects of BIM23014 were reversed by
      overexpression of protein kinase A catalytic subunit, indicating that SRIF does
      not act via serine/threonine phosphatases, but, rather, by lowering protein
      kinase A activity. These data define the components of the SRIF/SST2 receptor
      signaling pathway and provide important mechanistic insights into how SRIF
      controls neuroendocrine tumors. As SRIF analogs are effective antitumor agents,
      and many other related compounds are in development, the knowledge gained here
      will further our understanding of their mechanism of action in other malignancies
      as well.

PMID- 9178747
TI  - The mouse adrenocorticotropin receptor gene: cloning and characterization of its
      promoter and evidence for a role for the orphan nuclear receptor steroidogenic
      factor 1.
AB  - To elucidate the mechanism underlying the tissue-specific expression of the ACTH
      receptor/MC2 receptor (ACTH-R) in the adrenal cortex, we have cloned the mouse
      ACTH-R promoter. The analysis of the cDNA 5'-end showed an untranslated region of
      321 bp, and the ACTH-R gene was demonstrated to be composed of two exons of 113
      and 112 bp lying upstream of the single coding exon. S1 nuclease protection assay
      showed two major transcription start sites separated by 4 bp; 1.8 kb of the 5'
      flanking region inserted in a luciferase reporter vector had cell-specific
      promoter activity because it was functional only in mouse adrenocortical Y1 cells
      but not in mouse Leydig TM3 cells or fibroblast L cells. There was no dramatic
      change in the promoter activity in Y1 cells for all the deletions tested up to 
      113 bp upstream of the transcription start site. In contrast, expression in TM3
      cells was switched on from deletion -908 bp, while remaining undetectable in L
      cells. Site-directed mutagenesis of a steroidogenic factor 1 (SF1)-like site at
      position -25 bp resulted in a significant reduction in luciferase expression by
      the promoter in Y1 cells. Gel shift analysis of this site indicated specific
      binding of a protein in extracts of Y1 and TM3 cells. Moreover, expression of SF1
      in L cells induced promoter activity of the construct p(908). In conclusion, cell
      specific expression of the mouse ACTH-R appears to be controlled by at least two
      factors. One of them, most probably SF1, is responsible for steroidogenic cell
      specific expression. The other as yet unknown factor binding between position 
      1236 bp and -908 bp acts as a strong inhibitory factor in nonadrenal
      steroidogenic cells, resulting in the adrenal-specific expression of ACTH-R.

PMID- 9178748
TI  - Teleost FTZ-F1 homolog and its splicing variant determine the expression of the
      salmon gonadotropin IIbeta subunit gene.
AB  - Steroidogenic factor 1, a member of the fushi tarazu factor 1 (FTZ-F1) subfamily
      of nuclear receptors, is a key regulator in mammalian reproduction. From an
      embryonic complementary DNA library, the zebrafish homolog of FTZ-F1 (zFF1A) and
      an alternatively spliced variant (zFF1B) were isolated. zFF1B represented a C
      terminally truncated version of zFF1A. Whole mount in situ hybridization and
      reverse transcriptase-PCR analysis revealed that both zFF1A and B transcripts
      were present in the developing pituitaries, adult fish brain, gonads, and liver,
      albeit zFF1B messenger RNA was absent in testis. Comparison of the primary
      sequences of zFF1 with those of other FTZ-F1 subfamily members showed a close
      structural relationship between the mouse liver receptor homolog, which activated
      the alpha1-fetoprotein gene in rodent liver. However, similar to mouse
      steroidogenic factor 1, zFF1A regulated chinook salmon gonadotropin IIbeta
      subunit gene expression. On the contrary, zFF1B, which could bind a consensus
      gonadotrope-specific element with an affinity similar to that of zFF1A, lacked
      both the trans-activation function and synergistic interaction with the estrogen
      receptor. Furthermore, cotransfection studies in HeLa cells showed that zFF1B was
      a strong competitor for the action of zFF1A on the chinook salmon gonadotropin
      IIbeta subunit gene promoter. Our investigation suggests that 1) zFF1 represents
      an ancestor protein of the vertebrate FTZ-F1 homologs; 2) the antagonistic
      relationship between zFF1A and -B may dictate the expression of the FTZ-F1 target
      genes in a variety of tissues, including the pituitary; and 3) the naturally
      occurring zFF1B provides evidence that the C-terminal portion of zFF1A (80 amino
      acid residues) contains a major trans-activation function and a protein-protein
      interface.

PMID- 9178749
TI  - Multiple orphan nuclear receptors converge to regulate rat P450c17 gene
      transcription: novel mechanisms for orphan nuclear receptor action.
AB  - The orphan nuclear receptor steroidogenic factor-1 (SF-1) plays a key role in
      regulating the expression of the rat P450c17 gene in testicular Leydig and in
      adrenocortical cells. Other DNA sequences, not bound by SF-1, are also involved
      in transcriptional regulation of the rat P450c17 gene in both cell types. The
      region from -447/-399 or from -447/-419 increased both basal and cAMP-induced
      transcription, and the region from -418/-399 increased basal transcription to a
      greater extent than the intact -447/-399 DNA. The -447/-399 DNA sequence contains
      three imperfect copies of the orphan nuclear receptor-binding motif, AGGTCA, and
      at least three known orphan nuclear receptors, chicken ovalbumin upstream
      promoter transcription factor (COUP-TF), SF-1, and an early response gene induced
      by nerve growth factor (NGFI-B), bind to -447/-399 DNA. The AGGTCA triad is bound
      by one set of nuclear proteins when these three elements are colinear and is
      bound by a different set of proteins when these elements are separated. When the
      elements are separated, COUP-TF no longer binds, and the region -418/-399 is
      bound by a protein that greatly stimulates basal transcription. The region -447/
      419 is bound by two different proteins that mediate both basal and cAMP
      stimulated transcription. We call the protein binding to -418/-399 steroidogenic
      factor inducer of transcription-1 (StF-IT-1), and one of the proteins binding to 
      447/-419, StF-IT-2. SF-1 binds to a second AGGTCA element in the -447/-419
      region. StF-IT-1 and StF-IT-2 are both found in Leydig and adrenal cells, and
      transcriptional regulation is similar in both cell types. SF-1 and NGF-IB may
      increase transcription by displacing COUP-TF (a transcriptional repressor)
      because these proteins share DNA-binding domains. However, neither SF-1 nor NGF
      IB alone, binding as monomers, increases transcription. Rather, these proteins
      must interact with another DNA-binding protein, e.g. StF-IT-2, to increase
      transcription. StF-IT-2 also requires interaction with SF-1 (or NGF-IB) bound to
      DNA and cannot increase transcription by itself. This mechanism of action is
      different from the mechanism by which SF-1 regulates transcription from the -84/
      55 region of the rat P450c17 gene. Thus, we have defined a novel mechanism of
      action for orphan nuclear receptors that bind to DNA as monomers.

PMID- 9178750
TI  - The ERR-1 orphan receptor is a transcriptional activator expressed during bone
      development.
AB  - We studied the expression of estrogen-related receptor ERR-1 during mouse
      embryonic development. ERR-1 mRNA is present in bones formed by both the
      endochondral and intramembranous routes, and the onset of its expression
      coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but
      not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell
      lines as well as in primary osteoblastic cell populations derived from normal
      human bone. By gel shift analysis we found that ERR-1 binds as a monomer
      specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation
      analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are
      required for efficient ERR-1 binding. In transient transfection assays, ERR-1
      acts as a potent transactivator through the SFRE sequence. This effect is cell
      specific since ERR-1 activates transcription in the rat osteosarcoma cell line
      ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2
      cells. Notably, the osteopontin (a protein expressed by osteoblasts and released
      in the bone matrix) gene promoter is a target for ERR-1 transcriptional
      regulation. Our findings suggest a role for ERR-1 in bone development and
      metabolism.

PMID- 9178751
TI  - Fetal death in mice lacking 5alpha-reductase type 1 caused by estrogen excess.
AB  - Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter
      size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups
      in wild type controls. Oogenesis, fertilization, implantation, and placental
      morphology appear normal in the mutant animals. Fetal loss occurs between
      gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental
      androgen production and an induction of 5alpha-reductase type 1 expression in the
      decidua of wild type mice. Plasma levels of androstenedione and testosterone are
      2- to 3-fold higher on gestation day 9, and estradiol levels are chronically
      elevated by 2- to 3-fold throughout early and midgestation in the knockout mice.
      Administration of an estrogen receptor antagonist or inhibitors of aromatase
      reverse the high rate of fetal death in the mutant mice, and estradiol treatment
      of wild type pregnant mice causes fetal wastage. The results suggest that in the
      deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to
      estrogens, which in turn causes fetal death in midgestation. These findings
      indicate that the 5alpha-reduction of androgens in female animals plays a crucial
      role in guarding against estrogen toxicity during pregnancy.

PMID- 9178752
TI  - Two separate mechanisms for ligand-independent activation of the estrogen
      receptor.
AB  - Transient transfection experiments in which three different estrogen response
      element-containing reporter genes were cotransfected into HeLa cells, together
      with constitutively expressed estrogen receptor (ER) constructs, demonstrate that
      activation of the transcription of the reporter genes by epidermal growth factor
      (EGF) and by cholera toxin with 3-isobutyl-1-methyl-xanthine, which elevate
      cellular cAMP, is dependent upon the presence of functional ER. Cotransfection of
      the reporter genes with truncated versions of the ER shows that the two non
      ligand activators of ER require different regions of the receptor to produce
      their effects on transcription. EGF acts primarily by means of transactivation
      domain AF-1, whereas cAMP acts via transactivation domain AF-2 of the ER. A point
      mutation that removes a major site of inducible phosphorylation within the AF-1
      domain of the ER abolishes the response to EGF, but the response to estradiol and
      cAMP is retained. Specific inhibition of cAMP-activated protein kinase (protein
      kinase A) prevents the response to elevated cAMP but does not affect EGF or
      estradiol responses. Overexpression of the protein kinase A catalytic subunit in
      HeLa cells results in an amplified response to estradiol, similar to that induced
      by cholera toxin with 3-isobutyl-1-methyl-xanthine. Comparable experiments
      performed using COS-1 cells produce similar results but also reveal cell type-
      and promoter-specific aspects of the activation mechanisms. Apparently, the ER
      may be activated by three different signal molecules, estradiol, EGF, and cAMP,
      each using a mechanism that is distinguishable from that of the others.

PMID- 9178754
TI  - FLP recombinase/estrogen receptor fusion proteins require the receptor D domain
      for responsiveness to antagonists, but not agonists.
AB  - The ligand-binding domains of steroid receptors convey ligand-dependent
      regulation to certain proteins to which they are fused. Here we characterize
      fusion proteins between a site-specific recombinase, FLP, and steroid receptor
      ligand-binding domains. These proteins convert ligand binding into DNA
      recombination. Thus, ligand binding is directly coupled to an enzyme activity
      that is easily measured by DNA rearrangements or heritable genetic changes in
      marker gene expression, as opposed to the multiple events leading to
      transcription. Recombination by a FLP-estrogen receptor (FLP-EBD) fusion is
      activated by all tested estrogens, whether agonists or antagonists, indicating
      that all induce EBD release from the 90-kDa heat shock protein complex. Altering
      the distance between FLP and the EBD domain in the fusion proteins, by reducing
      the included length of the estrogen receptor D domain, affects ligand efficacy. A
      FLP-EBD with no D domain shows reduced inducibility by agonists and,
      unexpectedly, complete insensitivity to induction by all antagonists tested. A
      FLP-EBD including some D domain shows a ligand-inducible phenotype intermediate
      to those displayed by FLP-EBDs containing all or none of the D domain. Thus, we
      observed a tethered interference between FLP and the EBD domains that differs
      depending on the distance between the two domains, the conformations induced by
      agonists or antagonists, and which presents a previously undetectable distinction
      between estrogen agonists and antagonists in yeast.

PMID- 9178755
TI  - Disruption of the glucocorticoid receptor assembly with heat shock protein 90 by
      a peptidic antiglucocorticoid.
AB  - Association of glucocorticoid (GR) and progesterone (PR) receptors with a set of
      molecular chaperones, including the 90-kDa heat shock protein (hsp90), is a
      dynamic process required for proper folding and maintaining these nuclear
      receptors under a transcriptionally inactive, ligand-responsive state. Mutational
      studies of the chicken hsp90 complementary DNA suggested that three regions of
      this protein (A, B, and Z) interact with the hormone-binding domain of GR,
      whereas region A is dispensable for hsp90 binding to PR. We found that this 69
      amino acid region can be narrowed down to a 35-mer alpha-helical, acidic peptide,
      which is by itself able to inhibit hsp90 association to GR translated in vitro.
      The hsp90-free GR did not bind ligand, but was devoid of any specific DNA-binding
      activity, and higher peptide concentrations specifically inhibited the binding of
      activated GR to DNA. When overexpressed in cultured cells, this peptide acted as
      an antiglucocorticoid and inhibited the antiactivating protein-1 activity and the
      ligand-dependent nuclear transfer of GR. None of these effects, either in vivo
      and in vitro, was observed for PR. The region from residue 232 to residue 265 of
      hsp90 is, therefore, a domain critical for its association to GR, an association
      that is a prerequisite for receptor transcriptional activity. More importantly,
      these results demonstrate that targeting specific protein/protein interaction
      interfaces is a powerful means to specifically modulate nuclear receptor
      signaling pathways in a ligand-independent manner.

PMID- 9178753
TI  - Oligonucleotide squelching reveals the mechanism of estrogen receptor autologous
      down-regulation.
AB  - Antisense oligos complementary to the 5'-end, but not to the 3'-end, of the
      estrogen receptor (ER) messenger RNA caused a paradox accumulation of ER protein
      in MCF-7 cells. The same effect was observed after treatment of the cells with
      the corresponding sense oligos. The oligos interfering with ER down-regulation
      were demonstrated to specifically bind the ER with affinities in the nanomolar
      range. It is, therefore, proposed that the ER up-regulation induced by the oligos
      might be due to squelching of the ER (or ER-inducible proteins) from their
      binding site located in the 5'-end of the ER gene. We also report that
      transcriptionally inactive ER mutants can undergo down-regulation, and that in
      denaturing gels, the migration profile of ER-oligo and ER-estrogen-responsive
      element complexes are dissimilar. We, therefore, propose that ER can interact
      with DNA in different ways and at different binding sites. These observations
      might have important pharmacological consequences, since specific drugs could be
      devised to induce the ER conformation necessary to perform only selected tasks of
      the ER transcriptional repertoire.

PMID- 9178756
TI  - Progesterone receptor (PR) inhibits expression of insulin-like growth factor
      binding protein-1 (IGFBP-1) in human endometrial cell line HEC-1B:
      characterization of the inhibitory effect of PR on the distal promoter region of
      the IGFBP-1 gene.
AB  - Progestin has been shown to have both stimulatory and inhibitory effects on the
      expression of insulin-like growth factor binding protein-1 (IGFBP-1) in human
      endometrial cells. In this study, progestin was found to reduce levels of
      secreted IGFBP-1 and IGFBP-1 messenger RNA and IGFBP-1 promoter activity after
      stably transfecting a progesterone receptor (PR; B form) expression vector into
      HEC-1B cells. Deletion analysis of the IGFBP-1 promoter revealed that PR
      specifically inhibited promoter activity derived from a 59-bp distal BsaHI/RsaI
      fragment. It was concluded that PR inhibited the promoter activity through
      protein-protein interactions based on the facts that 1) no progesterone
      responsive element was revealed by a series block mutation in the BsaHI/RsaI
      fragment; 2) PR bound by the antiprogesterone ZK98299 inhibited IGFBP-1 promoter
      activity; 3) a DNA-binding mutant of PR inhibited the IGFBP-1 promoter activity;
      and 4) in an in vivo competition assay, the DNA-binding domain of PR did not
      release the inhibitory effect of intact PR. Analysis of PR deletion mutants
      indicated that both transcriptional activation domains of PR (TAF-1 and TAF-2)
      were involved in the inhibition of IGFBP-1 expression. Thus, our data may explain
      the superinduction of IGFBP-1 in human endometrial cells after progestin
      withdrawal or progestin replacement with antiprogestin.

PMID- 9178757
TI  - Localization of ligand-binding domains of human corticotropin-releasing factor
      receptor: a chimeric receptor approach.
AB  - Two CRF receptors, CRFR1 and CRFR2, have recently been cloned and characterized.
      CRFR1 shares 70% sequence identity with CRFR2, yet has much higher affinity for
      rat/human CRF (r/hCRF) than CRFR2. As a first step toward understanding the
      interactions between rat/human CRF and its receptor, the regions that are
      involved in receptor-ligand binding and/or receptor activation were determined by
      using chimeric receptor constructs of the two human CRFR subtypes, CRFR1 and
      CRFR2, followed by generating point mutations of the receptor. The EC50 values in
      stimulation of intracellular cAMP of the chimeric and mutant receptors for the
      peptide ligand were determined using a cAMP-dependent reporter system. Three
      regions of the receptor were found to be important for optimal binding of r/hCRF
      and/or receptor activation. The first region was mapped to the junction of the
      third extracellular domain and the fifth transmembrane domain; substitution of
      three amino acids of CRFR1 in this region (Val266, Tyr267, and Thr268) by the
      corresponding CRFR2 amino acids (Asp266, Leu267, and Val268) increased the EC50
      value by approximately 10-fold. The other two regions were localized to the
      second extracellular domain of the CRFR1 involving amino acids 175-178 and His189
      residue. Substitutions in these two regions each increased the EC50 value for
      r/hCRF by approximately 7- to 8-fold only in the presence of the amino acid 266
      268 mutation involving the first region, suggesting that their roles in peptide
      ligand binding might be secondary.

PMID- 9178758
TI  - Thyroid hormone inhibits the human prolactin gene promoter by interfering with
      activating protein-1 and estrogen stimulations.
AB  - Transcription of the human PRL (hPRL) gene in the pituitary is subject to tissue
      specific and multihormonal regulation involving two main regulatory regions, a
      proximal promoter and a distal enhancer. In this report we show that thyroid
      hormone inhibits the expression of the hPRL gene in rat pituitary cells.
      Transient expression experiments show that thyroid hormone regulation involves a
      strong inhibitory element, located in the proximal (-164/-35) promoter, which is
      modulated by a more distal stimulatory response control region. Gel retardation
      experiments reveal that the thyroid hormone receptor does not bind to the
      proximal negative element. We show the existence of an activating protein-1 (AP
      1) response element located at positions -61 to -54 of the proximal promoter,
      conferring AP-1 stimulation to the hPRL promoter. This AP-1 induction is
      abolished when hormone-bound thyroid hormone receptor is present, indicating that
      there is an interference between the thyroid hormone receptor and AP-1 regulatory
      pathways. Furthermore, using the complete hPRL upstream region, we show that
      estrogen induction is abolished by simultaneous thyroid hormone treatment.

PMID- 9178759
TI  - Growth hormone stimulates transcription of the gene encoding the acid-labile
      subunit (ALS) of the circulating insulin-like growth factor-binding protein
      complex and ALS promoter activity in rat liver.
AB  - The growth-promoting activity of GH, the principal hormonal determinant of body
      size, is mediated by insulin-like growth factor I (IGF-I). Most of the IGF-I in
      plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP
      3) and an acid-labile subunit (ALS). The 150-kDa complex serves as a reservoir of
      IGF-I and determines its bioavailability to the tissues. Formation of the 150-kDa
      complex depends upon the synthesis of ALS, which is synthesized primarily in
      liver and is regulated by GH. The present study demonstrates that GH stimulates
      ALS gene transcription in rat liver and ALS promoter activity in a rat hepatoma
      cell line. ALS messenger RNA (mRNA) and ALS nuclear transcripts were decreased to
      similar extents in the livers of GH-deficient hypophysectomized rats. GH
      increased hepatic ALS mRNA within 3-4 h to about 65% of the levels seen in sham
      operated control rats. To confirm that GH stimulated ALS gene transcription, we
      transiently transfected an ALS promoter-luciferase reporter gene construct into
      H4-II-E rat hepatoma cells and primary rat hepatocytes. Recombinant human GH
      (hGH) stimulated promoter activity about 3-fold. In contrast, basal promoter
      activity was lower, and GH stimulation was absent when the ALS reporter construct
      was transfected into GH-responsive 3T3-F442A mouse preadipocyte fibroblasts. GH
      stimulation of ALS promoter activity in H4-II-E cells was mediated by functional
      GH receptors; nonprimate (rat and bovine) GH gave identical stimulation to hGH,
      and stimulation by hGH occurred at physiological concentrations. Reverse
      transcriptase-PCR analysis indicated that GH receptor mRNA was present in H4-II-E
      cells at approximately 40% of the level seen in rat liver. GH also induced the
      expression of the endogenous c-fos gene, indicating that the signaling pathway
      necessary for the activation of gene expression by GH was intact in H4-II-E
      cells. Thus, H4-II-E cells are a GH-responsive liver cell line that should
      provide a useful system in which to study the molecular mechanism of
      transcriptional regulation by GH of ALS and other hepatic genes.

PMID- 9178760
TI  - Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated
      mainly by a multi-substrate docking-site.
AB  - Ufo/Axl belongs to a new family of receptor tyrosine kinases with an
      extracellular structure similar to that of neural cell adhesion molecules. In
      order to elucidate intracellular signaling, the cytoplasmic moiety of Ufo/Axl was
      used to screen an expression library according to the CORT (cloning of receptor
      targets) method. Three putative Ufo substrates were identified: phospholipase
      Cgamma1 (PLCgamma), as well as p85alpha and p85beta subunits of
      phosphatidylinositol 3'-kinase (PI3-kinase). Subsequently, chimeric EGFR/Ufo
      receptors consisting of the extracellular domains of the epidermal growth factor
      receptor (EGFR) and the transmembrane and intracellular moiety of Ufo were
      engineered. Using different far-Western blot analyses and coimmunoprecipitation
      assays, receptor binding of PLCgamma and p85 proteins as well as GRB2, c-src and
      lck was examined in vitro and in vivo. Competitive inhibition of substrate
      binding and mutagenesis experiments with EGFR/Ufo constructs revealed C-terminal
      tyrosine 821 (EILpYVNMDEG) as a docking site for multiple effectors, namely
      PLCgamma, p85 proteins, GRB2, c-src and lck. Tyrosine 779 (DGLpYALMSRC)
      demonstrated an additional, but lower binding affinity for the p85 proteins in
      vitro. In addition, binding of PLCgamma occurred through tyrosine 866
      (AGRpYVLCPST). Moreover, our in vivo data indicate that further direct or
      indirect binding sites for PLCgamma, GRB2, c-src and lck on the human Ufo
      receptor may exist.

PMID- 9178761
TI  - A novel human ERK phosphatase regulates H-ras and v-raf signal transduction.
AB  - A cDNA encoding a novel human extracellularly-regulated kinase (ERK) phosphatase,
      designated B59, was isolated from a B5/589 human mammary epithelial cell cDNA
      library. The 1104 nucleotide open reading frame encodes 368 amino acids including
      the highly conserved catalytic site sequence of protein phosphotyrosine
      phosphatases (PTPs), VXVHCXXGXXR, at amino acid position 276-287. The predicted
      70 amino acid stretch surrounding the HC motif shares significant sequence
      identity with other human dual specificity PTPs (dsPTPs), including the known ERK
      PTPs CL100, PAC1, B23, as well as the dsPTPs VH-1 and VHR. B59 protein
      synthesized in vitro in a rabbit reticulocyte lysate dephosphorylated rat ERK1
      and ERK2 proteins whose phosphorylation had been stimulated by v-mos kinase added
      to the lysate. Ectopic expression of B59 in NIH3T3 fibroblasts inhibited the
      induction of an oncogene-responsive promoter by the dominant-activating raf
      mutant, raf-BXB. Moreover, cotransfection of NIH3T3 cells with B59 inhibited
      morphological transformation by H-ras and v-raf oncogenes. These results suggest
      that B59 suppresses the transforming activity of H-ras or v-raf oncogenes through
      ERK dephosphorylation and inactivation.

PMID- 9178762
TI  - Specific changes in rasGAP-associated 62 kilodalton protein during integrin
      mediated cell-substrate interaction.
AB  - A cascade of signal transduction events is initiated when cells make contact with
      each other or with a substrate. The nature of these signal transduction pathways
      is beginning to be elucidated. In particular, adhesive interactions between cells
      and their substrate, mediated by cell-surface integrins and extracellular matrix
      proteins, appears to activate the MAP kinase pathway. Here we show that in mouse
      fibroblasts and rat epithelial cells, tyrosine phosphorylation of a 62 kilodalton
      rasGAP-associated protein (GAPa-p62) is decreased upon cell-substrate
      interaction. Interaction between fibroblasts and various extracellular matrices
      such as fibronectin, vitronectin and collagen IV, but not laminin, results in
      tyrosine dephosphorylation of GAPa-p62. Cell-substrate mediated tyrosine
      dephosphorylation of GAPa-p62 is defective in transformed cell lines, suggesting
      a possible role for p62 in tumorigenic transformation. These studies suggest that
      in fibroblasts, and perhaps even in epithelial cells, the signal transduction
      pathway(s) triggered by different integrin engagement events converge on the
      rasGAP protein and alter the tyrosine phosphorylation and/or association of GAPa
      p62.

PMID- 9178763
TI  - Differential regulation of interstitial collagenase (MMP-1) gene expression by
      ETS transcription factors.
AB  - Expression of interstitial collagenase (MMP-1) has been detected in stromal
      fibroblasts of various malignant tumors. Here, we have studied the effect of
      three structurally different ETS transcription factors (ETS-1, ERGB/Fli-1, and
      PU.1) on MMP-1 promoter activity in NIH3T3 fibroblasts. ETS-1 increased the
      activity of 3.8 kb MMP-1 promoter construct up to tenfold, while ERGB/Fli-1 or
      PU.1 alone had no marked effect on basal promoter activity. ETS-1 also markedly
      potentiated enhancement of MMP-1 promoter by both c-Jun and JunB, whereas
      ERGB/Fli-1 augmented only the effect of c-Jun. Interestingly, PU.1 abolished
      induction of MMP-1 promoter by both c-Jun and JunB. Stimulation of MMP-1 promoter
      by 12-O-tetradecanoyl phorbol-13-acetate and okadaic acid was differentially
      augmented by ETS-1 and ERGB/Fli-1, and abrogated by PU.1. Co-transfection studies
      with MMP-1 promoter 5'-deletion constructs revealed that AP-1 site was necessary
      for PU.1-elicited suppression. As compared to control cell lines, PU.1-positive
      stable cells exhibited clearly weaker binding of c-Jun and JunD containing AP-1
      complexes to MMP-1 promoter AP-1 element, as well as marked reduction in basal
      level and induction of c-jun mRNA by 12-O-tetradecanoyl phorbol-13-acetate and
      okadaic acid, suggesting a novel mechanism for PU.1-mediated inhibition of AP-1
      dependent gene expression. These results show that three structurally distinct
      ETS transcription factors differently modulate AP-1 dependent upregulation of MMP
      1 gene expression.

PMID- 9178764
TI  - Multiple neuroendocrine tumours in transgenic mice induced by c-kit-SV40 T
      antigen fusion genes.
AB  - Transgenic mice carrying either a 1.008 or a 4.225 kb of the mouse c-kit 5'
      flanking sequences linked to the oncogenic large T antigen (TAg) region of the
      simian virus 40 (SV40) genome were generated to test if the c-kit promoter could
      be used to develop useful mouse models. Both constructs promote tumourigenesis in
      the pituitary and the thyroid with high efficiency. The cell types from which
      each of these tumours derives were identified. Tumours of the pituitary derive
      from alpha-MSH-expressing cells located in the intermediate lobe. Transformed
      cells of the thyroid were calcitonin-positive, implying that the tumours derive
      from C cells or their precursors. Chromogranin A and neuron-specific enolase,
      general neuroendocrine cell markers, were expressed in both tumour types.
      Furthermore a variety of tumours appeared in the transgenic mice. Several of them
      stained positively for chromogranin A and/or neuron-specific enolase. This
      suggests a previously unsuspected tissue-specificity of the c-kit 5' flanking
      sequences for neuroendocrine cells. The Kit-TAg transgenic mouse lines may
      represent a valuable model for the study of the development and the biology of
      neuroendocrine tumours.

PMID- 9178765
TI  - Expression of a binding protein for FGF is associated with epithelial development
      and skin carcinogenesis.
AB  - Fibroblast growth factors (FGF)-1 and -2 are found in most embryonic and adult
      normal and tumor tissues, where they are immobilized in the extracellular matrix
      (EM). Mobilization of these FGFs is part of a tightly controlled process
      resulting in the activation of high-affinity receptors. Recently, we have shown
      that a novel human FGF-binding protein (FGF-BP) mediates the release of
      immobilized FGF-2 from the EM. Here we isolated genomic and cDNA clones of the
      mouse FGF-BP homologue and studied its expression during embryonic development
      and skin carcinogenesis. The murine gene contains two exons that generate a 1.2
      kb mRNA and predicts an 18 kDa secreted protein that is 63% identical to its
      human homologue. FGF-BP mRNA expression during embryogenesis is restricted to
      skin, intestine and lung. In the developing skin, FGF-BP expression starts at
      embryonic day 9, reaches peak levels perinatally and is downregulated during
      postnatal development. Development regulation in the intestine is similar, but in
      lungs and ovaries high expression was also observed in the adult. FGF-BP mRNA
      expression in the adult skin is dramatically increased during early stages of
      carcinogen-induced transformation in vivo and by ras-activation in vitro.
      Finally, mouse FGF-BP binds to FGF-2 and can function as a modulator of FGF in
      FGF-responsive cells. Our results suggest a potential function of FGF-BP during
      development and tumorigenesis.

PMID- 9178766
TI  - The carboxy terminus of p53 mimics the polylysine effect of protein kinase CK2
      catalyzed MDM2 phosphorylation.
AB  - The oncogene product MDM2 can be phosphorylated by protein kinase CK2 in vitro
      0.5-1 mol of phosphate were incorporated per mol MDM2 protein. The catalytic
      subunit of protein kinase CK2 (alpha-subunit) catalyzed the incorporation of
      twice as much phosphate into the MDM2 protein as it was obtained with the
      holoenzyme. Polylysine stimulated MDM2 phosphorylation by CK2 holoenzyme
      threefold in contrast to the alpha-subunit-catalyzed MDM2 phosphorylation which
      was reduced by about 66% when polylysine was added. Full length p53, but also a
      peptide representing a C-terminal fragment of the tumor suppressor gene product
      p53 (amino acids 264-393 which also harbors the CK2beta interaction site at amino
      acids 287-340) mimicked the polylysine effect in all respects, ie. stimulation of
      phosphate incorporation by CK2 holoenzyme and inhibition in the presence of the
      catalytic CK2 alpha-subunit. Stimulation by p53(264-393) was on the average close
      to twofold and inhibition in the case of the alpha-subunit-catalyzed MDM2
      phosphorylation was about 40%. Phosphorylation of MDM2 by CK2 holoenzyme in the
      presence of the p21(WAF1/CIP1), known to be a potent inhibitor of cyclin
      dependent protein kinases, also led to a significant reduction of phosphate
      incorporation into MDM2 indicating that p21(WAF1/CIP1) does not exclusively
      inhibit cell cycle kinases. Furthermore, these data add new insight into the
      autoregulatory loop which include p21(WAF1/CIP1), MDM2 protein, CK2 and p53.

PMID- 9178767
TI  - Differential regulation of the human Wilms tumour suppressor gene (WT1) promoter
      by two isoforms of PAX2.
AB  - PAX2 is a member of the paired box family of genes with an important role in
      kidney, genital tract and eye development. Another gene essential for kidney and
      genital tract development is the Wilms tumour gene, WT1. PAX2 and WT1 encode
      transcription factors expressed during fetal kidney development in patterns that
      overlap both spatially and temporally. The overlap of PAX2 and WT1 expression in
      fetal kidney prompted us to determine whether PAX2 regulates the WT1 gene. To
      investigate this possibility, the WT1 promoter and a series of WT1 promoter
      deletion fragments were cloned into a luciferase reporter vector, and used in co
      transfection experiments with PAX2 expression constructs. PAX2 transactivated the
      WT1 promoter up to 35-fold in CHO-K1 cells, and from four- to sevenfold in 293
      cells. Two regions of the WT1 promoter were required in the same promoter
      construct for efficient transactivation by PAX2 in CHO-K1 cells, and purified
      recombinant PAX2 protein was found to bind to two sites in the WT1 promoter, at 
      205/-230 and +377/+402. Removal of WT1 promoter sequences containing the -205/
      230, or +377/+402 binding sites abolished transactivation of the WT1 promoter by
      PAX2 in CHO-K1 cells, and had a differential effect on transactivation of the WT1
      promoter in 293 cells, depending on the PAX2 isoform used. A fragment containing
      the -205/-230 site alone could be transactivated by PAX2. These findings suggest
      that PAX2 is a tissue-specific modulator of WT1 expression, and is involved in
      cell growth control via WT1.

PMID- 9178768
TI  - The genetic penetrance of the activated neu oncogene for the induction of mammary
      cancer in vivo.
AB  - Carcinogenesis is most often viewed as a multistage disease process. An exception
      to this was suggested for neu transformation of mammary cells in a transgenic
      model (Muller et al., 1988); however, this interpretation is controversial
      (Bouchard et al., 1989). In order to better define neu mammary transformation in
      vivo, we directly measured the genetic penetrance of the neu oncogene. Mammary
      cells in situ were infected with replication-defective retroviral vectors
      carrying the activated neu oncogene (pJRneu). A limiting dilution in vivo
      transplantation assay was used to measure the percentage of mammary clonogenic
      (stem-like) cells that stably and functionally integrated this vector. Based on
      this, the percentage of clonogens integrating and expressing neu that could
      progress to mammary carcinomas was quantified to estimate the penetrance of this
      gene in mammary carcinogenesis. The genetic penetrance of neu was 3.6% (95%
      confidence interval 2.2%-5.8%). This high degree of genetic penetrance is
      compatible with the observations that certain neu-transgenic mice develop a very
      great number of mammary carcinomas (Muller et al., 1988). However, whether these
      data are compatible with a single-step transformation model (100% penetrance) is
      uncertain and is discussed.

PMID- 9178769
TI  - D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the
      Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding
      sites.
AB  - The c-Cbl proto-oncogene encodes a multidomain phosphoprotein that has been
      demonstrated to interact with a wide range of signalling proteins. The
      biochemical function of c-Cbl in these complexes is, however, unclear. Recent
      studies with the C. elegans Cbl homologue, sli-1, have suggested that Cbl
      proteins may act as negative regulators of EGF receptor (EGFR) signalling. As the
      EGFR and other protein tyrosine kinase receptor signalling pathways are highly
      conserved between insects and vertebrates, we sought a Drosophila homologue of c
      Cbl for a detailed genetic analysis. We report here that Drosophila melanogaster
      has a single gene, D-cbl, that is homologous to c-cbl. We find that D-cbl encodes
      a 52 kDa protein that has a high degree of similarity to c-Cbl and SLI-1 across
      novel phosphotyrosine-binding (PTB) and RING finger domains. Surprisingly,
      however, D-Cbl is C-terminally truncated relative to c-Cbl and SLI-1 and
      consequently is unable to bind SH3-domain containing adaptor proteins, including
      the Drosophila Grb2 homologue, Drk. Although the D-Cbl protein lacks Drk binding
      sites it can nevertheless associate with a tyrosine phosphorylated protein, or is
      itself tyrosine phosphorylated in an DER dependent manner and associates with
      activated Drosophila EGF receptors (DER) in vivo. Consistent with a role for D
      Cbl in DER dependent patterning in the embryo and adult, D-Cbl is expressed at a
      high level in early embryos and throughout the imaginal discs in third instar
      larvae. This study forms the basis for future genetic analysis of D-Cbl, aimed at
      gaining insights into the role of Cbl proteins in signal transduction.

PMID- 9178770
TI  - The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A.
AB  - A yeast two-hybrid screen has identified HBP1 as a transcription factor capable
      of interacting with the pocket protein family. We show that HBP1 can interact
      with one of these, RB, both in vitro and in mammalian cells. Two distinct RB
      binding sites are present within HBP1--a high affinity binding site, mediated by
      an LXCXE motif and a separate low affinity binding site present within an
      activation domain. GAL4-fusion experiments indicate that HBP1 contains a masked
      activation domain. Deletion of two independent N- and C-terminal inhibitor
      domains unmasks an activation domain which is 100-fold more active than the full
      length protein. The released activation capacity is repressed by RB, p130 and
      p107. In addition, E1A can repress the activity of HBP1 via conserved region 1
      sequences in a manner independent of the CBP co-activator. We show by stable
      expression in NIH3T3 cells that HBP1 has the capacity to induce morphological
      transformation of cells in culture.

PMID- 9178771
TI  - Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain
      containing protein.
AB  - In a previous large scale screen for differentially expressed genes in pancreatic
      cancer, we identified a gene highly overexpressed in cancer encoding a novel
      protein with four K-homologous (KH) domains. KH-domains are found in a subset of
      RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the
      fragile X mental retardation gene product (FMR1). By fluorescence in situ
      hybridization (FISH) the identified gene named koc (KH domain containing protein
      overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were
      localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740
      bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains
      eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580
      amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K).
      The koc transcript is highly overexpressed in pancreatic cancer cell lines and in
      pancreatic cancer tissue as compared to both, normal pancreas and chronic
      pancreatitis tissue. High levels of expression were as well found in tissue
      samples of other human tumours. As the KH domain has been shown to be involved in
      the regulation of RNA synthesis and metabolism, we speculate that koc may assume
      a role in the regulation of tumour cell proliferation by interfering with
      transcriptional and or posttranscriptional processes. However, the precise role
      of koc in human tumour cells is unknown and remains to be elucidated.

PMID- 9178772
TI  - Increased transcription of the E mu-myc transgene and mRNA stabilisation produce
      only a modest elevation in Myc protein.
AB  - Mice bearing the E mu-myc transgene, which links the immunoglobulin heavy chain
      enhancer (E mu) with c-myc, are predisposed to developing B cell lymphomas.
      Several B lineage cell lines have been isolated from these animals, and some have
      been converted to macrophages following infection with v-raf. In this study we
      compared the regulation of myc expression in E mu-myc B lymphoma lines, their
      macrophage counterparts and other non-myc transformed B cell lines. Nuclear run
      on analyses demonstrated that transcription of the transgene was elevated in E mu
      myc B cell lines. Moreover, the presence of a 600 bp phiX174 marker in the 3' end
      of the transgene produced a marked stabilisation of this RNA species.
      Consequently, steady state myc mRNA levels in the E mu-myc B lymphoma cells were
      tenfold higher than the macrophage derivatives and non-myc transformed B lineage
      lines. Despite the considerable difference in myc RNA levels, the E mu-myc B cell
      lines contained only 30-50% more Myc protein than the other cell lines. This
      discrepancy between RNA and protein content was not due to increased degradation
      of the protein as the half life was normal in the transgenic cell lines. These
      results indicate that both E mu and phiX174 sequences influence transgenic myc
      expression and that protein levels do not correlate with RNA content in E mu-myc
      cell lines.

PMID- 9178773
TI  - AAD wants to convert sun worshippers.

PMID- 9178774
TI  - Encouraging trend on prescription drug information.

PMID- 9178776
TI  - From the Centers for Disease Control and Prevention. Media dissemination of and
      public response to the Ultraviolet Index--United States, 1994-1995.

PMID- 9178775
TI  - No plateau for HIV/AIDS epidemic in US women.

PMID- 9178777
TI  - From the Centers for Disease Control and Prevention. Contraceptive practices
      before and after an intervention promoting condom use to prevent HIV infection
      and other sexually transmitted diseases among women--selected US sites, 1993
      1995.

PMID- 9178778
TI  - From the Centers for Disease Control and Prevention. Outbreaks of cyclosporiasis-
      United States, 1997.

PMID- 9178779
TI  - From the Centers for Disease Control and Prevention. Varicella-related deaths
      among adults--United States, 1997.

PMID- 9178780
TI  - Underrecognition of dementia by caregivers cuts across cultures.

PMID- 9178781
TI  - Underrecognition of dementia by caregivers cuts across cultures.

PMID- 9178782
TI  - Underrecognition of dementia by caregivers cuts across cultures.

PMID- 9178783
TI  - Primary prevention of cardiovascular disease endpoints using beta-blockers.

PMID- 9178784
TI  - Can ambulatory monitoring identify high-risk patients with stable coronary artery
      disease?

PMID- 9178785
TI  - Fiber intake and risk of developing non-insulin-dependent diabetes mellitus.

PMID- 9178786
TI  - Fiber intake and risk of developing non-insulin-dependent diabetes mellitus.

PMID- 9178787
TI  - Virginia Apgar and the Apgar score: kudos and a correction.

PMID- 9178788
TI  - Variations in cataract extraction rates in Medicare prepaid and fee-for-service
      settings.
AB  - OBJECTIVE: To compare rates of cataract extraction in 2 prepaid health settings
      and in traditional fee-for-service (FFS) settings. DESIGN: A cross-sectional
      analysis using 1993 health maintenance organization (HMO) Medicare claims and
      encounter files, the Health Care Financing Administration (HCFA) 5% Medicare Part
      B provider/supplier file, and the HCFA October 1992 100% Medicare population
      file. SETTING: Southern California Medicare FFS settings and the staff-model and
      independent practice association (IPA) plans of a large California HMO. PATIENTS:
      1993 Medicare beneficiaries aged 65 years and older. The study included 43387
      staff-model HMO enrollees, 19050 IPA enrollees, and 47 150 FFS beneficiaries (a
      5% sample of all Southern California FFS beneficiaries). MAIN OUTCOME MEASURE:
      Age and risk-factor adjusted rates of cataract extraction per 1000 beneficiary
      years. RESULTS: After controlling for age, sex, and diabetes mellitus status, FFS
      beneficiaries were twice as likely to undergo cataract extraction as were prepaid
      beneficiaries (P<.01). Female FFS beneficiaries were nearly twice as likely to
      undergo the procedure as were male FFS beneficiaries (P<.001); there were no
      extraction rate differences by sex in the prepaid settings. CONCLUSION: Because
      of the potential implications for vision care in the elderly, the significantly
      different rates of cataract extraction in FFS and prepaid settings warrant
      further clinical investigation to determine whether there is overuse in FFS vs
      underuse in prepaid settings. Such investigations must assess the appropriateness
      of cataract surgery by evaluating its use relative to clinical need.

PMID- 9178789
TI  - Psychoactive substance use disorders among seriously injured trauma center
      patients.
AB  - OBJECTIVE: To assess the prevalence of psychoactive substance use disorders
      (PSUDs) among a large, unselected group of seriously injured trauma center
      patients, using a standardized diagnostic interview and criteria. DESIGN:
      Prevalence study. SETTING: A level I regional trauma center. PATIENTS: Trauma
      center patients fulfilling the following criteria were eligible subjects: aged 18
      years or older, admission from injury scene, length of stay of 2 days or longer,
      and intact cognition. OUTCOME MEASURES: The PSUDs were diagnosed using the
      Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of
      Mental Disorders, Revised Third Edition (DSM-III-R) and were categorized as abuse
      or dependence and past or current (within past 6 months). The SCID results were
      analyzed with respect to demographic factors, injury type, and blood alcohol
      concentration and urine toxicology results, using chi2 and logistic regression
      techniques. RESULTS: Of the 1220 patients approached for study, 1118 (91.6%)
      consented. More than half (54.2%) had a diagnosis of a PSUD in their lifetime.
      Approximately 90% of alcohol and other drug use diagnoses were for dependence and
      more than 62% were current. Overall, 24.1% of patients were currently alcohol
      dependent (men, 27.7%; women, 14.7%; P<.001), and 17.7% were currently dependent
      on other drugs (men, 20.2%; women, 11.2%; P<.001). Current alcohol dependence
      rates were not associated with race; rates of dependence on other drugs were
      higher among nonwhites and victims classified with intentional injuries. While
      54.3% of blood alcohol-positive patients were currently alcohol dependent and
      38.7% of patients with positive urine screening test results for drugs other than
      alcohol and nicotine were currently drug dependent, 11.7% of blood alcohol
      negative and 3.9% of drug-negative patients, respectively, had current diagnoses
      of dependence on psychoactive substances. CONCLUSIONS: A high percentage of
      seriously injured trauma center patients are at risk of having current PSUDs.
      Patients with positive toxicology screening test results and/or positive
      screening questionnaire responses should be referred for formal evaluation and
      treatment.

PMID- 9178791
TI  - Use of lumbar radiographs for the early diagnosis of low back pain. Proposed
      guidelines would increase utilization.
AB  - OBJECTIVE: The Agency for Health Care Policy and Research (AHCPR) has recently
      published guidelines for the management of patients with acute low back pain,
      which include recommendations for the use of lumbar radiographs, based on the
      identification of "red flags" for fractures, tumors, or infections. The purpose
      of this study was to evaluate the potential impact of these guidelines in
      patients with new episodes of low back pain seen in primary care settings.
      DESIGN: Retrospective cohort study. SETTING: Four family clinics (18 physicians)
      in Edmonton, Alberta. PATIENTS: The records of all patients seen in 1992 and 1993
      with a new episode of low back pain were reviewed: 963 patients had a history of
      back pain of less than 3 months. OUTCOME MEASURES: Lumbar radiograph utilization
      at the initial low back pain visit. Charts were also reviewed to determine
      subsequent occurrence of spinal tumors, infection, or fractures that could be
      related to low back pain. RESULTS: One hundred twenty-seven (13%) of the 963
      patients with acute low back pain had lumbar radiographs during their first
      visit, 68 (54%) with oblique views. If the AHCPR guidelines had been applied to
      this population, 426 (44%) of the patients would have undergone radiography,
      increasing current utilization by 238%. Eight of the 963 patients had a diagnosis
      of fracture or bone tumor during follow-up. The sensitivity of the guidelines to
      potentially detect these diseases was higher than the physicians' utilization
      patterns, but their specificity and positive predictive values were low.
      CONCLUSIONS: The implementation of the AHCPR guidelines for the initial use of
      radiographs in patients with low back pain may increase utilization and economic
      costs. A more restricted and cost-efficient set of guidelines should be proposed.

PMID- 9178790
TI  - Plasma homocysteine as a risk factor for vascular disease. The European Concerted
      Action Project.
AB  - CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic
      vascular disease, but the strength of the relationship and the interaction of
      plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish
      the magnitude of the vascular disease risk associated with an increased plasma
      homocysteine level and to examine interaction effects between elevated plasma
      homocysteine level and conventional risk factors. DESIGN: Case-control study.
      SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases
      of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800
      controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total
      homocysteine was measured while subjects were fasting and after a standardized
      methionine-loading test, which involves the administration of 100 mg of
      methionine per kilogram and stresses the metabolic pathway responsible for the
      irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'
      phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure
      were also measured. RESULTS: The relative risk for vascular disease in the top
      fifth compared with the bottom four fifths of the control fasting total
      homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine
      loading identified an additional 27% of at-risk cases. A dose-response effect was
      noted between total homocysteine level and risk. The risk was similar to and
      independent of that of other risk factors, but interaction effects were noted
      between homocysteine and these risk factors; for both sexes combined, an
      increased fasting homocysteine level showed a more than multiplicative effect on
      risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin,
      and pyridoxal phosphate, all of which modulate homocysteine metabolism, were
      inversely related to total homocysteine levels. Compared with nonusers of vitamin
      supplements, the small number of subjects taking such vitamins appeared to have a
      substantially lower risk of vascular disease, a proportion of which was
      attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased
      plasma total homocysteine level confers an independent risk of vascular disease
      similar to that of smoking or hyperlipidemia. It powerfully increases the risk
      associated with smoking and hypertension. It is time to undertake randomized
      controlled trials of the effect of vitamins that reduce plasma homocysteine
      levels on vascular disease risk.

PMID- 9178792
TI  - Child health services research. Challenges and opportunities.
AB  - The characteristics of childhood as a unique developmental stage of life, the
      continuity of child health with adult health, and a distinctive child health care
      system justify a separate focus of health services research on children. Child
      health services research (CHSR) currently lacks the tools necessary to monitor
      the impact of health system change on children's health and health care and to
      compare the effectiveness of alternative treatment modalities. There is an urgent
      need to build the research capacity of this field of inquiry. Ignoring or
      minimizing attention to CHSR is both shortsighted and ultimately costly for
      families and the entire nation. We present arguments for why children merit a
      separate focus in health services research, identify factors that have led to the
      failure of appropriate development of CHSR, and offer a set of strategies for how
      to build the research capacity of the field.

PMID- 9178793
TI  - Prevention of bacterial endocarditis. Recommendations by the American Heart
      Association.
AB  - OBJECTIVE: To update recommendations issued by the American Heart Association
      last published in 1990 for the prevention of bacterial endocarditis in
      individuals at risk for this disease. PARTICIPANTS: An ad hoc writing group
      appointed by the American Heart Association for their expertise in endocarditis
      and treatment with liaison members representing the American Dental Association,
      the Infectious Diseases Society of America, the American Academy of Pediatrics,
      and the American Society for Gastrointestinal Endoscopy. EVIDENCE: The
      recommendations in this article reflect analyses of relevant literature regarding
      procedure-related endocarditis, in vitro susceptibility data of pathogens causing
      endocarditis, results of prophylactic studies in animal models of endocarditis,
      and retrospective analyses of human endocarditis cases in terms of antibiotic
      prophylaxis usage patterns and apparent prophylaxis failures. MEDLINE database
      searches from 1936 through 1996 were done using the root words endocarditis,
      bacteremia, and antibiotic prophylaxis. Recommendations in this document fall
      into evidence level III of the US Preventive Services Task Force categories of
      evidence. CONSENSUS PROCESS: The recommendations were formulated by the writing
      group after specific therapeutic regimens were discussed. The consensus statement
      was subsequently reviewed by outside experts not affiliated with the writing
      group and by the Science Advisory and Coordinating Committee of the American
      Heart Association. These guidelines are meant to aid practitioners but are not
      intended as the standard of care or as a substitute for clinical judgment.
      CONCLUSIONS: Major changes in the updated recommendations include the following:
      (1) emphasis that most cases of endocarditis are not attributable to an invasive
      procedure; (2) cardiac conditions are stratified into high-, moderate-, and
      negligible-risk categories based on potential outcome if endocarditis develops;
      (3) procedures that may cause bacteremia and for which prophylaxis is recommended
      are more clearly specified; (4) an algorithm was developed to more clearly define
      when prophylaxis is recommended for patients with mitral valve prolapse; (5) for
      oral or dental procedures the initial amoxicillin dose is reduced to 2 g, a
      follow-up antibiotic dose is no longer recommended, erythromycin is no longer
      recommended for penicillin-allergic individuals, but clindamycin and other
      alternatives are offered; and (6) for gastrointestinal or genitourinary
      procedures, the prophylactic regimens have been simplified. These changes were
      instituted to more clearly define when prophylaxis is or is not recommended,
      improve practitioner and patient compliance, reduce cost and potential
      gastrointestinal adverse effects, and approach more uniform worldwide
      recommendations.

PMID- 9178794
TI  - Users' guides to the medical literature. XIII. How to use an article on economic
      analysis of clinical practice. B. What are the results and will they help me in
      caring for my patients? Evidence-Based Medicine Working Group.

PMID- 9178795
TI  - Should rates of cataract surgery vary by insurance status?

PMID- 9178796
TI  - Policies for posting biomedical journal information on the Internet.
      International Committee of Medical Journal Editors.

PMID- 9178797
TI  - A piece of my mind. My father's hands.

PMID- 9178798
TI  - Managed care as a target of distrust.

PMID- 9178799
TI  - Managed care and the competitive market in health care. What they can and cannot
      do.

PMID- 9178800
TI  - Dysregulated expression of transforming growth factor beta and its type-I and
      type-II receptors in basal-cell carcinoma.
AB  - In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly
      homologous isoforms that exert their effects via heteromeric complexes of type-I
      and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and
      metabolism of various cell types, including keratinocytes. We have investigated
      the immunohistological localization of TGF-beta1, TGF-beta2, TbetaR-I and TbetaR
      II in normal human skin, basal-cell carcinoma (BCC), Bowen's disease, seborrheic
      keratosis, eccrine poroma and eccrine spiradenoma using frozen tissue specimens.
      In normal human skin, the immunoreactive TGF-beta2, but not TGF-beta1, was
      detected predominantly in the epidermis, follicles and sebaceous glands. The
      epidermal expression of TbetaR-I and TbetaR-II was very weak in the majority of
      normal skins. In BCC, TGF-beta2 expression was markedly reduced or completely
      negative. In addition, TbetaR-I- and TbetaR-II-positive stromal cells were
      accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly
      but moderately positive for TGF-beta1. Decreased expression of TGF-beta2 was
      likely to be associated with the differentiation state of BCC cells, since TGF
      beta2 expression was clearly observed in the squamoid foci of BCC. In addition,
      no expression of TGF-beta2 was detected in the eccrine secretory portion or in
      eccrine spiradenoma, but it was detected in the upper eccrine ducts and in
      eccrine poroma.

PMID- 9178801
TI  - Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a
      clinico-pathological and immuno-histochemical population-based study of 32
      patients.
AB  - The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL)
      appearing in the same individual indicates a closer relationship between the 2
      diseases than previously believed. The purpose of our study was to analyze cases
      of HD and NHL in a defined population clinically, histopathologically and
      immunohistochemically to look for similarities indicating a common cellular
      origin. Between 1974 and 1994, 77 individuals were identified from the Swedish
      Cancer Registry and the National Health Care Programme for HD as potentially
      having both diagnoses. Thirty-two patients who had both HD and NHL were available
      for histo-pathological re-examination and immunohistochemical staining with CD30,
      CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The
      most common relation was HD preceding a high-grade malignant NHL (16 of 32
      patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next
      common association was NHL of B-CLL type followed by HD (7 of 32 patients). At
      clinical presentation, the first lymphoma did not differ from lymphomas not
      associated with a second lymphoma, whereas the second one often appeared with a
      disseminated and aggressive clinical form. There was a significant correlation
      between the expression of p53 and LMP in first and second lymphomas. CD3 antibody
      was frequently expressed both in HD and NHL, whereas positivity for B-cell
      related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower
      than previously described. The occurrence of HD and NHL in an individual is
      unusual. Tumour biological features common to both HD and NHL may indicate a
      similar cellular origin, regardless of the time interval between the diagnoses,
      and may contribute to the understanding of the pathogenesis of lymphoma.

PMID- 9178802
TI  - Cancer risk after renal transplantation in Japan.
AB  - Excess of cancer in patients receiving renal transplantation is well-known in
      Western countries, but information in Japan remains limited. Our study examined
      whether excess risk is found in patients receiving renal transplantation in
      Japan. Between 1970 and 1995, 1155 males and 589 females underwent renal
      transplantation in 6 hospitals, and a total of 12,982 person-years of observation
      was accumulated. Malignancies developed in 2.6% of patients; O/E ratio was 2.78.
      Median interval from renal transplantation to tumor development was 58 months.
      The interval in the patients receiving medication with cyclosporine-A (CyA)
      (median, 42.5 months) was significantly shorter than that with non-CyA (median,
      95.5 months). Median age at the diagnosis of malignancy was 40 years, which is
      much younger than that in the general population. Relative risk was highest in
      renal cancer, followed by thyroid cancer, malignant lymphoma and uterine cancer.
      A distribution of malignancies was different from that reported from Western
      countries. These findings showed the excess risk of malignancies in Japan with
      renal transplants, especially in male patients, similar to that observed in
      Western countries, though the types of malignancy were different.

PMID- 9178803
TI  - Immunocytochemical monitoring of micrometastatic disease: reduction of prostate
      cancer cells in bone marrow by androgen deprivation.
AB  - Occult dissemination of tumor cells mainly determines the prognosis of patients
      with primary prostate cancer. The effect of androgen deprivation on
      micrometastatic tumor cells in these patients is currently unknown. We therefore
      used an immunocytochemical assay with monoclonal antibodies (MAbs) directed
      against epithelial cytoskeleton proteins (i.e., cytokeratins) to monitor the
      concentration of isolated tumor cells in the bone marrow of 36 prostate cancer
      patients (stage C), who underwent hormonal androgen deprivation with Flutamide
      and Leuprorelin acetate. Tumor cells in cytologic bone marrow preparations were
      detected using an assay that employed the MAb CK2 directed against cytokeratin
      (CK) 18 and the alkaline anti-alkaline phosphatase staining method. Prior to
      therapy, we detected between 1 and 38 CK-positive cells per sample of 2 x 10(6)
      nucleated cells in 21 patients, while the remaining 15 patients displayed tumor
      free marrow samples. There was no significant correlation between the
      concentration of CK-positive cells and the volume of hypo-echogenic lesions as an
      indicator of the primary tumor volume or the serum level of prostate-specific
      antigen (PSA). After androgen deprivation, 20 of the 21 initially positive
      patients either became negative (n = 16) or showed at least a reduction in the
      concentration of CK-positive cells (n = 4). Moreover, only 2 of the 15 patients
      with negative pre-treatment findings became positive. All of the 7 patients with
      remaining tumor cells in the bone marrow after therapy showed no detectable
      amounts of PSA in their serum. Our findings suggest that serum PSA concentration
      is no indicator of micrometastatic disease in bone marrow. Neoadjuvant androgen
      deprivation appears to eliminate disseminated CK-positive tumor cells present in
      bone marrow, a preferred site of overt metastasis in prostate cancer patients.

PMID- 9178804
TI  - Steroid receptor measurement in breast cancers: comparison between ligand binding
      and enzyme-immunoassay in cytosolic and nuclear extracts.
AB  - We have analysed cytoplasmic and nuclear extracts of breast-cancer tissue from a
      total of 799 patients, measuring both oestrogen and progesterone receptors (ER,
      PR) using either the ligand binding assay (LBA) or the enzyme immunoassay
      technique (EIA). Mean and median receptor levels were much lower than those
      widely reported by others. For ER, this may in part be a consequence of the
      younger median age of the patient group. The frequency of positivity, using
      consensus cut-off values for clinical evaluation, was also lower than that
      reported by the EORTC Receptor Study Group. Although the measurements comparing
      the 2 methods were statistically correlated in terms of positivity, based on the
      above criteria for clinical assessment, concordance was considered to be
      relatively poor, particularly for ER when assayed in the same samples by the 2
      methods. In cytosolic but not nuclear extracts, the LBA method gave a higher
      median value for ER than the EIA (except in the group that had EIA values greater
      than 15 fmol/mg protein); for PR, median values were higher with EIA in both cell
      fractions. There was an excellent correlation between receptor amounts in
      cytosolic and nuclear extracts for both ER and PR using the EIA; this was
      significantly better than with LBA. We also observed a correlation between ER and
      PR in both cytosolic and nuclear fractions which was most pronounced when the
      analysis was done by EIA. The amounts of ER in the cytosolic fraction were also
      correlated with the those of PR in the nuclear fraction and ER in the nuclear
      fraction with PR in the cytosolic fraction, but only when the EIA method was
      used. We conclude that the EIA method appears to be more sensitive and gives
      biologically more reliable results. However, the disagreement between the methods
      may be due to legitimate recognition of altered forms of the receptor and may be
      of biological significance. Although the presence of receptor in the cytosolic
      fraction is artifactual, its measurement by EIA does parallel the amounts of
      nuclear receptor, which may be a more relevant biological parameter.

PMID- 9178806
TI  - Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6
      fatty acids and the risk of prostate cancer.
AB  - Ecological and case-control studies have demonstrated a positive correlation
      between consumption of fat and the risk of prostate cancer. Two recent human
      studies have focused on alpha-linolenic acid as a risk factor for prostate
      cancer. Animal experiments have shown that dietary omega-6 polyunsaturated fatty
      acids have generally stimulated tumour development, whereas omega-3
      polyunsaturated fatty acids have diminished it. The aim of our study was to
      investigate the association between these fatty acids and the subsequent risk of
      prostate cancer. Blood donors to the Janus serum data bank in Norway, who later
      developed prostate cancer, were matched to blood donors without prostate cancer
      (141 matched sets); the proportional level of fatty acids measured before
      diagnosis in the donors' serum was examined. The risk of later prostate cancer
      was analysed by conditional logistic regression. Increasing risk for prostate
      cancer was found with increasing quartiles of palmitoleic, palmitic and alpha
      linolenic acid. An inverse risk association was found with increasing levels of
      tetracosanoic acid, for the ratios of linoleic to alpha-linolenic acid and
      arachidonic to eicosapentaenoic acid. There was no clear association between the
      risk effect of total omega-3 and total omega-6 fatty acids. There were no
      indications of a relationship between fatty acids and more aggressive cancers.
      Our results verify recent findings of a positive association between alpha
      linolenic acid and a negative association between the ratio of linoleic to alpha
      linolenic acid and the risk of prostate cancer.

PMID- 9178805
TI  - Expression of alpha and beta genes of human chorionic gonadotropin in lung
      cancer.
AB  - To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung
      cancer, we attempted to detect the presence of mRNA transcripts of the alpha and
      beta genes for hCG in lung cancer tissues obtained from surgical operations.
      Although we were able to show the presence of hCG beta mRNA transcripts in lung
      cancer tissue by Northern blot, the sensitivity of the assay was too low for a
      precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse
      transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts
      of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the
      14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12
      normal lung tissues from the same patients. Our results are consistent with a
      clear difference in serum and urinary hCG beta levels observed between normal
      subjects and lung cancer patients. The expression of the hCG alpha gene, however,
      was detected in normal lung tissues more frequently than in lung cancer tissues
      using RT-PCR Southern blot. Our results strongly suggest the production of hCG
      beta as being part of the phenotype of malignantly transformed lung cells and
      further strengthen its superior specificity over intact hCG or hCG alpha as a
      tumor marker for lung cancers.

PMID- 9178807
TI  - Mass screening for neuroblastoma and mortality in birth cohorts.
AB  - Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and
      the whole of Japan was investigated to evaluate the effects of a high-performance
      liquid chromatography (HPLC) mass screening program, targeting on 6 month-old
      infants. In Sapporo City, the non-HPLC screened cohort showed no reduction in
      mortality at 4 years of age compared with the pre-screening cohort. However, the
      HPLC screened cohort showed a reduction of 69% in mortality compared with the pre
      screening cohort. On a nation-wide scale, there was a significant decline in
      mortality for the non-HPLC screened cohort compared with the pre-screening
      cohort; for the HPLC screened cohort for 1989-1991, there was also a reduction in
      mortality for children younger than 2 years of age. The incidence of
      neuroblastoma at 1-4 years of age in the HPLC cohort in Sapporo City was about
      half that in the pre-screening cohort, along with and probably because of an
      increasing incidence among infants in the same cohort. Our findings suggest that
      HPLC screening may detect some poor-prognosis neuroblastoma cases at early
      stages, thus providing for more favorable therapy.

PMID- 9178808
TI  - Altered mRNA expression of specific molecular species of fucosyl- and sialyl
      transferases in human colorectal cancer tissues.
AB  - Human colorectal cancers express various cancer-associated carbohydrate
      determinants such as Lewis Y or sialyl Lewis A, suggesting a considerable
      alteration in glycosyltransferase activities occurring upon malignant
      transformation. We investigated the mRNA amounts of fucosyltransferase (Fuc-T)
      and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V, VI and VII and
      ST-3N, ST-30 and ST-4, in human colorectal cancer tissues by Northern blotting
      and RT-PCR. Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not
      significantly altered, and only Fuc-T IV mRNA showed a moderate increase in
      cancer tissues when compared with adjacent non-malignant colonic epithelia taken
      from the same patient (273 +/- 96%; p < 0.001). The moderate increase of Fuc-T IV
      message may be related to an enhanced expression of Lewis Y in colon cancer
      tissues. In the ST isoenzymes, mRNA for ST-3N remained unchanged, whereas that
      for ST-4 decreased significantly in cancer tissues, to 32 +/- 29%, (p < 0.005).
      The most remarkable finding was that the message of ST-30 was prominently
      increased in cancer tissues compared with non-malignant colorectal mucosa. When
      further investigated by quantitative RT-PCR assays on a larger series of patients
      with colorectal cancers, the average increase in mRNA for ST-30 was 459 +/- 200%
      compared with that in adjacent non-malignant epithelium (significant at p <
      0.0001). The increase of ST-30 message was more prominent in the cancer tissues
      strongly expressing sialyl Lewis A than in the cancer tissues expressing sialyl
      Lewis A only weakly or moderately (significant at p < 0.05). The marked increase
      in the message of ST-30 is suggested to be related to an enhanced expression of
      sialylated carbohydrate determinants in colon cancer tissues including sialyl
      Lewis A, since the enzyme exhibited a significant activity against the type 1
      chain carbohydrate substrate and produced the precursors for sialyl Lewis A
      synthesis, when its cDNA was expressed in Cos-7 cells.

PMID- 9178809
TI  - Isolation and characterization of a novel gene from human glioblastoma multiforme
      tumor tissue.
AB  - Using the technique of DD-PCR (differential display-polymerase chain reaction) we
      isolated a novel gene (D2-2) that is overexpressed in glioblastoma multiforme
      tissue (GMT) as compared to normal brain tissue (NBT). D2-2 is also highly
      expressed in recurrent glioma, colon tumor metastatic to brain, breast tumors,
      prostate tumors and a prostate tumor cell line (LNCaP). Northern blot analysis
      showed that D2-2 is highly expressed in several tumor cell lines (MOLT
      lymphoblastic leukemia, SW480 colorectal adrenocarcinoma, A549 lung carcinoma, HL
      60 promyelocytic leukemia, S3 HeLa cells, K-562 chronic myelogeneous leukemia and
      G361 melanoma) as compared to NBT. Additionally, D2-2 is very highly expressed in
      cell lines derived from glioblastomas, grade IV astrocytomas, normal human fetal
      astrocytes (NHFA) and glioma. D2-2 is moderately expressed in neuroblastoma,
      neuroectodermal and medulloblastoma tumor cell lines. D2-2 expression is
      localized to the frontal lobe, occipital lobe and the cerebellum in the normal
      brain. Normal tissues such as thyroid, stomach, adrenal cortex, small intestine
      and pancreas show high expression of D2-2. We also show that D2-2 is expressed 28
      fold higher in fetal brain (20 weeks) than in adult brain. Sequence analysis of a
      2.0-kb fragment for D2-2 shows no homology to known sequences in the data base.

PMID- 9178810
TI  - Down-regulation of protein and mRNA expression for transforming growth factor
      beta (TGF-beta1) type I and type II receptors in human prostate cancer.
AB  - Transforming growth factor-beta (TGF-beta1) is a potent negative regulator of
      cell growth that transduces signals through interactions with type I and II
      receptors. Abnormal expression and mutational alterations of these receptors have
      been observed in several human malignancies. In this study, we investigated the
      expression of the two types of TGF-beta1 receptors, R-I and R-II, in a normal
      human prostate, primary prostate adenocarcinoma and lymph nodes with metastatic
      deposits. Expression of receptor proteins was examined by immunohistochemical
      analysis in paraffin-embedded prostatic tissue sections, and mRNA expression was
      determined by Northern blot and RT-PCR analysis. Uniformly strong
      immunoreactivity for both TGF-beta receptor proteins, R-I and R-II, was
      exclusively localized to the prostatic glandular epithelium of normal prostates.
      In contrast, tumor epithelial cells in primary and metastatic prostatic cancer
      specimens exhibited a weak heterogeneous immunoreactivity for both R-I and R-II
      receptors; 25% of primary prostatic tumors and 45% of the lymph nodes with
      metastases were totally negative for R-I and R-II expression, while the rest
      exhibited a significantly reduced immunoreactivity for both types of receptors
      compared to the normal prostate (p < 0.05). Moreover, there was a significant
      decrease in the expression of R-I and R-II mRNA, in all 20 primary prostatic
      tumors and 4 lymph nodes positive for metastases, indicating that the decreased
      protein expression was due to down-regulation of gene expression for the two
      receptors. Our findings imply that decreased expression of TGF-beta1 type I and
      type II receptors might be involved in prostate tumorigenesis.

PMID- 9178811
TI  - Chromosome 16 in primary prostate cancer: a microsatellite analysis.
AB  - Cytogenetic and molecular genetic analyses of prostate cancer specimens have
      revealed nonrandom chromosomal deletions, affecting chromosomes 7q, 8p, 10q and
      16q. Based on these data, we designed this study to further characterize the
      altered region(s) on chromosome 16 by evaluating 16 microsatellite markers on a
      population composed of 32 paired normal and primary prostatic tumor samples. The
      16 microsatellites selected mapped to 11 distinct loci on 16q and 5 loci on 16p.
      No alterations were identified affecting 16p. However, 16 of 31 (51%) informative
      cases showed molecular alterations in at least one of the loci analyzed on 16q,
      consisting of 18 deletions and 11 bandshifts. Moreover, most of the deletions
      clustered at 6 microsatellite loci, mapping to the 16q22.1-23.1 region. Our
      results suggest that microsatellite alterations on the long arm of chromosome 16
      are frequent events in prostate cancer, and that the 16q22.1-23.1 region might
      harbor a tumor suppressor gene involved in prostate cancer.

PMID- 9178812
TI  - MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating
      urothelial carcinomas.
AB  - Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas.
      Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+
      and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated
      over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens
      confirmed this observation, and indicated that CD4+ T cells surrounded the tumor
      islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five
      short-term carcinoma cell lines established from these urothelial tumors were
      used as target cells in cytolysis assays in order to investigate the functional
      anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL
      lines displayed MHC-class-I-dependent cytotoxicity directed against autologous
      tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed
      that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally,
      experiments performed on 6 allogeneic urothelial-cancer cell lines matched for
      HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward
      tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in
      urothelial carcinomas are functional and may participate in the anti-tumor immune
      response.

PMID- 9178813
TI  - The genes for gonadotropin-releasing hormone and its receptor are expressed in
      human breast with fibrocystic disease and cancer.
AB  - While gonadotropin-releasing hormone (GnRH) or GnRH receptor (GnRHR) have been
      reported to exist in tissues other than brain and pituitary, there is no report
      concerning co-expression of GnRH and GnRHR in human breast tissues. To address
      this question, we have examined whether mRNA for GnRH as well as GnRHR was
      present in different human breast samples, by employing the reverse transcription
      polymerase chain reaction (RT-PCR) protocol followed by Southern blotting of the
      PCR products. Coexpression of GnRH and GnRHR genes was further confirmed by dot
      blot hybridization using appropriate [32P]-labeled probes. We thus tested
      fibrocystic breast (4 cases), invasive ductal carcinomas (6 cases) and 1 adjacent
      non-neoplastic tissue. GnRHR and GnRH mRNAs were found in all actin-positive
      samples including malignant as well as nonmalignant tissues. Quantitative
      determinations of mRNA did not reveal significant differences between malignant
      and non-malignant breast samples for either GnRH or GnRHR gene expression. Our
      data show that neither gene was overexpressed in the breast cancer samples
      compared with normal breast tissue. Since GnRH agonists inhibit breast epithelial
      cell growth, the presence of GnRHR mRNA suggests that GnRH may specifically
      affect breast cell growth. Our data thus raise the possibility of an
      autocrine/paracrine role for GnRH in human mammary gland.

PMID- 9178814
TI  - Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757
      Norwegian men and women.
AB  - The relationship between dietary habits and subsequent risk of cutaneous
      malignant melanoma (CMM) was studied in 25,708 men and 25,049 women aged 16-56
      years attending a Norwegian health screening in 1977-1983. Linkage to the Cancer
      Registry of Norway and the Central Bureau of Statistics of Norway ensured a
      complete follow-up until December 31, 1992. Diet was recorded through a semi
      quantitative food-frequency questionnaire at the time of screening, and 108 cases
      of CMM were identified during follow-up. Use of cod liver oil supplementation and
      intake of polyunsaturated fat were associated with significant increased risk and
      drinking coffee with significant decreased risk of CMM in women. Adjusting for
      height, body mass index, body surface area, education, smoking or occupational or
      recreational physical activity did not change the results. No significant
      association was found between the incidence of CMM and any of the dietary factors
      in men. Important aspects are residual confounding by sun exposure and social
      class, as well as concern with multiple comparisons.

PMID- 9178815
TI  - Inhibition of growth and enhancement of differentiation of colorectal carcinoma
      cell lines by MAb MR6 and IL-4.
AB  - We have previously shown that expression of gp200-MR6, a molecule that is
      functionally associated with the interleukin-4 receptor (IL-4R), is lost from
      breast carcinoma cells as malignancy increases. Here we have analysed a series of
      colorectal carcinoma cell lines and show a similar decrease with increasing
      malignancy. Moreover, analysis of the HRA-19 cell line, which can exhibit a
      poorly or a well-differentiated phenotype according to culture conditions, shows
      that gp200-MR6 is weakly expressed on the former but strongly expressed on the
      latter. Functional analysis using either IL-4 or monoclonal antibody (MAb) MR6
      and the well-differentiated cell line SW1222 revealed that MAb MR6 acts as an
      agonist for IL-4, with both reagents causing a dose-dependent inhibition of cell
      division, but greatly enhancing the glandular differentiation of SW1222 in three
      dimensional collagen gels. These observations suggest that the gp200-MR6 molecule
      may act as the product of a tumour suppressor gene and that its loss may be a
      primary event in tumourigenesis.

PMID- 9178816
TI  - Liver endothelial E-selectin mediates carcinoma cell adhesion and promotes liver
      metastasis.
AB  - E-selectin is a cytokine-inducible endothelial cell adhesion receptor which is
      involved in the process of leukocyte rolling, the first in a cascade of
      interactions leading to leukocyte transmigration. Several studies have implicated
      this receptor in carcinoma cell adhesion to the endothelium, an interaction
      thought to be required for tumor extravasation during metastasis. To study the
      role of this receptor in the process of metastasis, we utilized a murine
      carcinoma line H-59 which is highly metastatic to the liver in vivo. When
      adhesion of H-59 cells to primary cultures of murine hepatic endothelial cells
      was measured, it was found that the tumor cells had a low basal level of adhesion
      to the sinusoidal endothelial cells, which could be significantly and
      specifically augmented by pre-activation of the endothelial cells with rTNF
      alpha. This incremental increase in adhesion to the activated endothelium could
      be completely and specifically abolished by a neutralizing monoclonal antibody to
      murine E-selectin (MAb 9A9). Similar results were obtained with 2 highly
      metastatic human colorectal carcinoma lines, HM 7 and CX-1, but not with a second
      murine subline, M-27, which is poorly metastatic to the liver. To assess the role
      of E-selectin in metastasis to the liver in vivo, the effect of MAb 9A9 on
      experimental liver metastasis was evaluated using the syngeneic H-59 model. We
      show here that this antibody caused a marked, specific and Fc-independent
      inhibition of experimental liver metastasis, reducing the median number of
      metastases by 97% relative to the control groups. Our results provide evidence
      that endothelial E-selectin is a mediator of carcinoma metastasis to the liver.

PMID- 9178817
TI  - Involvement of Ras in the expression of glycolipid sulfotransferase in human
      renal cancer cells.
AB  - Glycolipid sulfotransferase activity in a human renal cell carcinoma cell line,
      SMKT-R3, is enhanced by epidermal growth factor (EGF); tyrosine kinase inhibitors
      suppress this enhancement. To investigate the involvement of Ras in the signal
      transduction pathway from the EGF receptor to the expression of glycolipid
      sulfotransferase, we introduced v-H-ras into SMKT-R3 cells. In a quiescent state,
      the percent GTP bound to Ras in v-H-ras-expressing cells increased about 2.5-fold
      compared with control cells, suggesting that v-Ras introduced into the renal
      cancer cells is in an active form without EGF stimulation. Glycolipid
      sulfotransferase activity in v-H-ras-expressing cells was higher than in control
      cells. The sulfotransferase activity was affected neither by EGF nor by
      genistein, a tyrosine kinase inhibitor, in v-H-ras-expressing cells, whereas it
      was enhanced by EGF and reduced by genistein in control cells. Our observations
      suggest that Ras mediates the regulation pathway of glycolipid sulfotransferase
      activity in SMKT-R3 cells.

PMID- 9178818
TI  - Preventive effect of IgG from EBV-seropositive donors on the development of human
      lympho-proliferative disease in SCID mice.
AB  - The effect of weekly treatments with various gammaglobulin preparations on the
      development of human B-cell tumors was studied in severe combined immunodeficient
      (SCID) mice. SCID mice were injected i.p. with human peripheral blood mononuclear
      cells (PBMCs) from an Epstein-Barr virus (EBV)-seropositive healthy blood donor.
      Repopulated SCID mice were divided into 7 treatment groups receiving either PBS,
      2 commercial gammaglobulin preparations, purified IgG prepared from pooled plasma
      from EBV-seronegative or -seropositive blood donors, a rabbit anti-serum against
      EBV envelope glycoprotein gp340 or interferon (IFN)-alpha. All treatments started
      1 day after injection of PBMC and continued for 8 weeks. In the PBS-treated
      control group, 85% of mice developed tumors in the abdominal cavity, mostly with
      liver metastasis within 150 days. Tumor formation was prevented by treatment with
      the 2 commercial gammaglobulin preparations as well as by purified IgG from EBV
      seropositive donors. In contrast, purified IgG from EBV-seronegative donors,
      rabbit anti-gp340 anti-serum or IFN-alpha had no effect. Our results indicate
      that the effect of gammaglobulin is due to the presence of specific antibodies
      against EBV antigens. Further experiments showed that both the time of onset and
      the duration of treatment, as well as the dose of Ig, are important factors for
      prevention of tumor formation. Studies aiming at identification of target
      antigens for antibodies which prevent lymphoma development may be clinically
      relevant for prevention and possibly treatment of lympho-proliferative disease in
      severely immuno-compromised patients.

PMID- 9178819
TI  - Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA
      class-I, HLA class-II and ICAM-1 molecules.
AB  - IL-10 is a cytokine which shows various effects including inhibition of T-cell
      proliferation or HLA-dependent antigen presentation. In this study, we analysed
      the effects of exogenous or autocrine IL-10 on proliferation and expression of
      immunocritical surface molecules. Fourteen cultures of human melanoma cells were
      established from primary melanomas, locoregional lymph-node or distant
      metastases. In 5 melanoma cell cultures, proliferation in the presence of IL-10,
      anti-IL-10 antibodies (Ab) or control Ab was assessed with colorimetric and
      [3H]thymidine uptake assays. Flow cytometric analysis was used to quantify the
      expression of human leukocyte antigen (HLA) class-I, HLA class-II and
      intercellular adhesion molecule (ICAM)-1 and the IL-10 receptor (IL-10R). IL-10
      production of melanoma cells was documented by RT-PCR and IL-10 protein was
      detected in the supernatants by means of ELISA. IL-10 enhanced proliferation and
      prolonged survival of melanoma cells in 5 out of 5 cultures. Anti-IL-10 Ab
      decreased proliferation. IL-10R expression was found in 12 out of 14 (86%)
      melanoma cell cultures. The expression of HLA-I, HLA-II and ICAM-1 on all
      melanoma cells that were positive for IL-10R showed a reduction of 10-60% by IL
      10, whereas the surface levels of HLA-I, HLA-II and ICAM-1 in 5 out of 5 cell
      cultures revealed an increase of 10-170% by anti-IL-10 Ab. These findings suggest
      that IL-10 is an autocrine growth factor with significant impact on
      immunocritical molecules in melanoma. IL-10 effects have to be considered when
      planning therapeutic immunointerventions in melanoma patients.

PMID- 9178820
TI  - Cloning and expression of the recombinant FAb fragment of monoclonal antibody K1
      that reacts with mesothelin present on mesotheliomas and ovarian cancers.
AB  - The monoclonal antibody (MAb) K1 recognizes an approximate 40 kDa glycoprotein,
      mesothelin, that is present on the surface of human mesothelial cells,
      mesotheliomas and ovarian cancers. We have cloned the cDNAs encoding the variable
      regions of MAb K1 and constructed plasmids for expression of recombinant K1(FAb).
      Recombinant FAb was produced in Escherichia coli in inclusion bodies that were
      solubilized and refolded to active protein. Binding of K1 MAb and FAb was
      compared by radioactive binding and competition assays and by surface plasmon
      resonance (BIAcore). Recombinant K1(FAb) binds to cells expressing K1-antigen
      with a similar affinity as papain derived FAb from K1(IgG) and with a 4- to 10
      fold reduced affinity compared with bivalent IgG. The cloned FAb can be used to
      make higher affinity antibodies and immunoconjugates that could be useful for
      various types of immunotherapies.

PMID- 9178821
TI  - Adhesion of HT-29 colon carcinoma cells to E-selectin results in increased
      tyrosine phosphorylation and decreased activity of c-src.
AB  - Adhesion of metastatic cancer cells at secondary sites is known to be regulated
      by several families of adhesion proteins, including selectins and integrins.
      Colon carcinoma cells have been shown to tether to and roll on both stimulated
      endothelial cells and purified E-selectin. We have demonstrated that HT-29 human
      colon carcinoma cells adhere specifically to an E-selectin-IgG chimera. Upon
      adhesion to E-selectin, the amount of tyrosine phosphorylation of several
      proteins in HT-29 cell lysates increases compared with cells in bovine serum
      albumin-coated wells on phosphotyrosine Western blots; this increase is
      statistically significant. This effect is specific for adhesion to E-selectin,
      since addition of an E-selectin blocking monoclonal antibody (MAb), E3, to the
      wells causes a statistically significant decrease in tyrosine phosphorylation
      relative to E-selectin alone on phosphotyrosine Western blots. One protein that
      is affected this way has been identified as c-src. Kinase assays show a dose
      dependent and statistically significant decrease in c-src activity upon adhesion
      to E-selectin, which correlates with an increase in phosphorylation of Tyr 527,
      the negative regulatory tyrosine. CnBr digestion of 32P-labeled c-src shows an
      increase in phosphorylation of tyrosine 527 after adhesion to E-selectin. Our
      results may identify a signaling pathway involving the E-selectin ligand on HT-29
      cells and c-src.

PMID- 9178822
TI  - Secretion of N-(4-hydroxyphenyl) retinamide-retinol-binding protein from liver
      parenchymal cells: evidence for reduced affinity of the complex for
      transthyretin.
AB  - The synthetic retinoid 4-HPR has been shown to markedly lower the plasma
      concentration of both retinol and RBP in rats and humans. We have studied the
      effect of 4-HPR on the secretion of retinol-RBP from liver cells in vivo and in
      vitro. In rats maintained with a normal diet, a vitamin A-deficient diet or a
      normal diet supplemented with 4-HPR, chylomicrons [3H]retinyl esters were rapidly
      cleared from the plasma. The secretion of chylomicron-derived [3H]retinol from
      tissues to the circulation, however, was different. In control rats, the lymph
      derived [3H]retinol peaked after about 2 hr, whereas 4-HPR treatment effectively
      reduced this peak of [3H]retinol. Our results suggest that 4-HPR inhibits
      secretion of retinol-RBP from the liver. Therefore, we decided to study the
      effect of 4-HPR on the secretion of RBP using the human hepatoma cell line HepG2.
      Retinol and 4-HPR were found to induce the secretion of RBP. The medium from
      cells treated with 4-HPR was immunoprecipitated with antibodies against human
      RBP. HPLC analysis of the precipitated RBP revealed the presence of 4-HPR. When
      the medium from cells incubated with either 4-HPR or retinol was applied to a TTR
      affinity column, we found that RBP from cells incubated with 4-HPR had a
      considerably reduced affinity for TTR. We conclude that 4-HPR binds RBP and
      thereby induces secretion of RBP in HepG2 cells, and that the secreted 4-HPR-RBP
      complex has a reduced affinity for TTR. This observation may explain the 4-HPR
      induced reduction of plasma retinol and RBP observed in in vivo studies.

PMID- 9178824
TI  - Growth inhibition and apoptotic cell death in uterine cervical carcinoma cells
      induced by 5-fluorouracil.
AB  - We have investigated the effects of 5-fluorouracil (5-FU) on cell growth, DNA
      synthesis, morphological changes, DNA fragmentation and Fas antigen expression of
      cultured human uterine cervical carcinoma cells (OMC-1 squamous-cell carcinoma
      and OMC-4 adenocarcinoma). Apoptotic cell death in cervical carcinoma tissues
      from the patients after an intravenous administration of 5-FU was also examined.
      Treatment of OMC-1 and OMC-4 cells with 0.1-10 microg/ml of 5-FU (1 microg/ml =
      7.7 microM) resulted in concentration-dependent inhibition of the number of
      cumulative viable cells and 6-3H-deoxyuridine uptake into the DNA. These effects
      of 5-FU were well correlated with apoptotic indices of the cells determined in
      situ by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end
      labeling (TUNEL). A TUNEL signal was detectable in nuclei of normal-looking cells
      and in a lobulated nucleus with dense chromatin. DNA fragmentation was observed
      in the cells exposed to 10 microg/ml of 5-FU according to the nucleosomal ladder
      detected by electrophoresis. Flow cytometric analysis showed that Fas antigen
      expression of the cells increased upon incubation with 10 microg/ml of 5-FU.
      Moreover, TUNEL of tissue sections of resected uterus revealed that apoptosis
      occurred more frequently in patients treated pre-operatively with 500 mg/m2/day
      of 5-FU for 8 days than in those who did not receive 5-FU. These results suggest
      that achievable therapeutic levels of 5-FU inhibit cell growth and DNA synthesis
      and induce apoptotic cell death in uterine cervical carcinoma cells. However, the
      relationship between 5-FU-mediated apoptosis and the Fas ligand/Fas system
      remains to be explored.

PMID- 9178823
TI  - Radioimmunotherapy of experimental pancreatic cancer with 131I-labeled monoclonal
      antibody PAM4.
AB  - We examined the therapeutic efficacy of 131I-labeled murine monoclonal antibody
      (MAb) PAM4 against human pancreatic cancers carried as xenografts in athymic nude
      mice. Animals bearing the CaPan1 tumor (0.2 cm3) were either untreated or were
      given, 131I-labeled nonspecific Ag8 antibody. By week 7 mean tumor size had grown
      16.5 +/- 8.4-fold and 4.2 +/- 2.5-fold for the untreated and 131I-Ag8-treated
      animals, respectively. In contrast, animals administered 131I-PAM4 exhibited
      marked regression of tumors to an average of 15% of initial tumor volume. Since
      most pancreatic cancer patients present with large tumor burdens, the limitation
      of 131I-PAM4 treatment with respect to initial tumor size was investigated in
      animals bearing tumors of approximately 0.5 cm3, 1.0 cm3 and 2.0 cm3. Significant
      extension of survival time (>3-fold increase) was noted for both the 0.5 cm3 and
      1.0 cm3 131I-PAM4-treated groups, compared to their respective untreated
      controls. Even in the group bearing large 2.0-cm3 tumors, survival was increased
      2-fold over the control group. To further improve anti-tumor effects in large
      tumors, 2 injections of 131I-PAM4 were administered at a 4-week interval to
      animals bearing tumors of approximately 1.0 cm3. Significant extended survival
      was noted for the group receiving 2 doses when compared to the group receiving
      only 1 dose.

PMID- 9178826
TI  - Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.
AB  - We have shown that the oval cell line OC/CDE 22 can be transformed by the highly
      carcinogenic fjord-region diol epoxides of benzo[c]phenanthrene. Mutational
      activation of the ras proto-oncogene family has been proposed to be a critical
      event in the formation of tumors induced by polycyclic aromatic hydrocarbons.
      Therefore, we investigated whether in the earlier transformed OC/CDE 22 cells any
      point mutations were detected in the ras proto-oncogene. The results indicate
      that the malignant transformation of OC/CDE 22 cells by the 4 stereoisomeric
      benzo[c]phenanthrene diol epoxides in vitro is independent of activation of the
      Ha-ras proto-oncogene. In addition, Northern and Western blot analyses revealed
      no overexpression of the Ha-ras protooncogene in the transformed OC/CDE 22 cell
      lines. However, transfection of the OC/CDE 22 cells with an activated Ha-ras
      oncogene malignantly transformed the OC/CDE 22 cells, and the transfected cells
      served as precursor cells of tumors with a cholangiocellular morphology and
      phenotype. Our latter finding reinforces the view that OC/CDE 22 cells are
      committed to the bile duct epithelial cell lineage.

PMID- 9178825
TI  - Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive
      to 5-fluorocytosine.
AB  - To investigate the potential use of E. coli cytosine deaminase (CD) gene instead
      of the commonly used HSV-TK gene in the gene therapy of brain tumors, we
      constructed a retrovirus vector carrying the CD gene. We then transduced a rat
      glioma cell line C6 with CD gene by the retrovirus vector. Transduction of the CD
      gene made C6 cells become highly sensitive to the anti-fungi drug 5
      fluorocytosine (5FC). IC50 for 5FC was 6,000 microM in CD-negative cells, while
      it was 3 microM in CD-positive cells. Mixed cellular assay showed that CD
      positive cells had a strong "bystander effect" on CD-negative cells when exposed
      to 5FC. Significant anti-tumor effects were observed in nude mice bearing s.c.
      tumors derived from CD-positive cells when these animals were given 250 mg/kg 5FC
      twice a day for 20 consecutive days. A marked decrease in tumor weight occurred
      when a mixture containing 50% CD-positive and 50% CD-negative C6 cells was
      injected s.c., followed by 5FC treatment, suggesting the bystander effect in
      vivo. Concerning the pharmacokinetics of 5FC, especially its high oral bio
      availability and good penetration into cerebrospinal fluid, we suppose that the
      combination of CD-gene transfer and 5FC oral administration may have potential
      use in the gene therapy of brain tumors.

PMID- 9178827
TI  - Correlation of repressed transcription of alpha-tocopherol transfer protein with
      serum alpha-tocopherol during hepatocarcinogenesis.
AB  - Using a subtraction-enhanced display technique, we identified a rodent alpha
      tocopherol transfer protein (alpha-TTP) cDNA which exhibited markedly lower
      messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in
      healthy controls. Several lines of evidence have substantiated that abnormal
      alpha-TTP results in isolated vitamin E deficiency. In this study, we
      investigated the hepatic mRNA amounts of alpha-TTP during rat hepatic
      carcinogenesis and liver regeneration on Northern blot, localization of alpha-TTP
      mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the
      correlation between alpha-TTP mRNA and alpha-tocopherol. alpha-TTP mRNA
      concentrations of the rats were decreased at the early stage of hepatic
      carcinogenesis, and remained 3-5-fold reduced as the tumor progressed. In
      parallel, serum alpha-tocopherol concentrations were significantly decreased to
      40% of those in the controls at the early stages of rat hepatic carcinogenesis (p
      < 0.01). The 2 data sets were strongly correlated (r = 0.834, p < 0.001). In situ
      hybridization revealed that a decrease of alpha-TTP mRNA was preferentially
      localized in the tumor nodules of rats and humans with HCC. Our data suggest that
      repressed transcription of alpha-TTP is associated with a decrease of serum alpha
      tocopherol and with hepatic carcinogenesis.

PMID- 9178828
TI  - Activation of protein kinase C prevents induction of apoptosis by geranylgeraniol
      in human leukemia HL60 cells.
AB  - In a previous study, we showed that geranylgeraniol (GGO) is a potent inducer of
      apoptosis in human leukemia cells, including HL60 promyelocytic leukemia cells.
      The present study describes the effects of activators of protein kinase C (PKC)
      on GGO-induced apoptosis in various lines of leukemia cells. Both 12-O
      tetradecanoylphorbol-13-acetate (TPA) and diacylglycerol (DG) inhibited the GGO
      induced morphological changes that are characteristic of apoptosis and the DNA
      fragmentation. Similar effects were observed with other lines of human and murine
      leukemia cells such as ML1, U937, M1 and P388. Flow cytometric analysis also
      revealed that both TPA and DG prevented GGO-induced DNA degradation in a dose
      dependent manner. These inhibitory effects of TPA and DG were antagonized by
      inhibitors of PKC such as H-7 and staurosporin, and by amiloride, an inhibitor of
      Na+/H+ antiporter. In contrast to the inhibitory effects of TPA and DG on GGO
      induced apoptosis, 4alpha-TPA, which is unable to activate PKC, failed to prevent
      GGO-induced DNA fragmentation. However, the selective activator of PKC-beta, 12
      deoxyphorbol 13-phenylacetate 20-acetate, significantly inhibited GGO-induced DNA
      fragmentation. Our results suggest that PKC, and in particular the PKC-beta
      isoenzyme, might be involved in the process of GGO-induced apoptosis.

PMID- 9178830
TI  - Chronic lymphocytic leukemia and hairy-cell leukemia-diagnosis and treatment:
      results of a consensus meeting of the German CLL Co-operative Group.

PMID- 9178829
TI  - Interference of bcl-2 with intercellular control of carcinogenesis.
AB  - Induction of apoptosis in transformed fibroblasts by surrounding normal cells has
      been discussed as a potent early control step in carcinogenesis. According to
      this hypothesis, tumor progression should require resistance of transformed cells
      against this TGF-beta-triggered control mechanism. Here we show that Bcl-2, a
      protein involved in inhibition of apoptosis, can protect transformed cells from
      induction of apoptosis by surrounding cells. Rather than acting on the
      transformation process itself, Bcl-2 may thus represent an efficient modulator of
      carcinogenesis at an intercellular level.

PMID- 9178831
TI  - Prognostic factors in chronic lymphocytic leukemia.
AB  - The clinical course of chronic lymphocytic leukemia (CLL) shows a marked
      heterogeneity, with a median survival ranging from 2 to 20 years at different
      disease stages. This unpredictable course has inspired clinical hematologists and
      oncologists to search for parameters which predict survival and disease
      progression. This effort resulted in different staging systems, two of which, the
      Rai and Binet staging systems, have become most popular because of their
      simplicity. They identify three major groups of patients with different survival.
      Since patients at early stages have a relatively good prognosis, only advanced
      stages used to be treated by chemotherapy with alkylating agents. With the advent
      of potentially curative, but more aggressive treatment options for CLL,
      additional prognostic criteria are required to predict the outcome more
      precisely, in particular in young patients with early disease. It is the intent
      of this review to summarize the current knowledge on both established and new
      prognostic factors in CLL, some of which might help to define risk-adapted
      treatment protocols in the near future.

PMID- 9178832
TI  - First-line therapy of advanced chronic lymphocytic leukemia.
AB  - There is general agreement that patients with advanced chronic lymphocytic
      leukemia (CLL) should be treated if they develop anemia or thrombocytopenia. The
      combination of chlorambucil (CLB) and prednisone is often used for first-line
      therapy of these patients, but compared to monotherapy with CLB, no difference in
      survival could be demonstrated. Steroids should be generally reserved, therefore,
      for the management of complications such as hemolytic anemia and thrombocytopenia
      or other autoimmune manifestations. CLB can still be considered standard therapy
      for advanced CLL, since polychemotherapy protocols as well as newer agents such
      as fludarabine have failed to show an improvement in survival compared to CLB.
      However, the results regarding response and survival of the CLB-treated patients
      seem to depend on dosage intensity and treatment duration. Biological response
      modifiers such as interferons, interleukins, and monoclonal antibodies have not
      improved responses or remission duration. Because experiences with CLL patients
      are limited, the indications and procedure of bone marrow transplantation are not
      yet clear. However, since results of current treatment protocols are
      unsatisfactory, regardless of age, patients should be involved in clinical
      studies that address the question whether high-dose CLB, fludarabine or the
      combination of fludarabine with other active agents can improve patients'
      outcome. In addition, autologous and allogeneic bone marrow transplantation as a
      consolidation therapy is under study and might be a step towards a potential cure
      of this disease.

PMID- 9178833
TI  - Cytogenetic and molecular cytogenetic analysis of B cell chronic lymphocytic
      leukemia: specific chromosome aberrations identify prognostic subgroups of
      patients and point to loci of candidate genes.
AB  - The most frequent chromosome aberrations in B cell chronic lymphocytic leukemia
      (B-CLL) detected by conventional chromosome banding analysis are trisomy 12
      followed by structural abnormalities of the long arms of chromosomes 13, 14, and
      11. Complex karyotypes, trisomy 12, and a '14q+' abnormality have been associated
      with inferior prognosis, whereas aberrations of 13q have been found in patients
      with a favorable outcome. However, the cytogenetic analysis of B-CLL by
      conventional banding techniques has remained a difficult task mainly due to the
      low in vitro mitotic activity of the tumor cells. Although B cell mitogens are
      used for cell culture, clonal chromosome aberrations are detected in only half of
      the B-CLL tumors. 'Interphase cytogenetics' by means of fluorescence in situ
      hybridization (FISH) circumvents this problem, because there is no need to induce
      the malignant cells to proliferate in vitro. Numerical and structural chromosome
      aberrations can be detected in non-dividing interphase cells as well as in
      metaphase spreads. By FISH, the most common chromosome abnormalities are
      deletions of 13q followed by deletions of 11q, trisomy 12, and deletions of 17p.
      Except for the TP53 gene at 17p13, no candidate gene affected by these
      aberrations has so far been identified. FISH will be instrumental for the
      identification of such genes because the recurrent aberrations, especially
      deletions, can be systematically delineated to the resolution level of several
      kb. Furthermore, based on the sensitive detection of chromosome abnormalities by
      FISH, more accurate correlations between chromosome abnormalities and prognosis
      can be performed. Deletion of the TP53 gene at 17p13 have already been shown to
      be one of the most important independent prognostic factors for survival. Other
      specific aberrations of clinical significance will likely be identified by the
      systematic application of interphase cytogenetics on a large series of patients.

PMID- 9178834
TI  - Purine analogs in the treatment of chronic lymphocytic leukemia.
AB  - The purine analogs fludarabine (FAMP) and 2-chlorodeoxyadenosine (2-CDA) are
      highly active in chronic lymphocytic leukemia (CLL). In second-line therapy
      response rates are in the range of 30 to 60% and exceed 70% when applied to
      previously untreated patients. While FAMP in particular is thus well established
      for salvage treatment and can be considered as the present treatment of choice,
      more data are needed to define the role of purine analogs for first-line therapy.

PMID- 9178835
TI  - Present status of purine analogs in the therapy of chronic lymphocytic leukemias.
AB  - Chronic lymphocytic leukemia (CLL) is considered an incurable disease and
      therefore the management is palliative and more disease-related symptoms
      directed. Recently, the high activity of nucleoside analogs as fludarabine
      (FAMP), 2-chlorodeoxyadenosine (2-CDA) and 2-deoxycoformycin (DCF) in low-grade
      NHLs has caused a new reawakening interest in CLL concerning new treatment
      strategies, the biology and prognostic factors of this disease. Predominantly
      FAMP has widely been studied in CLL with impressive remission rates of 30-70%,
      including some complete remission (CR) in refractory or relapsed CLL. In
      previously untreated patients, the remission rate is about 80% with a CR rate of
      up to 60%. These results open new treatment strategies, even with a curative
      intention such as high-dose chemotherapy combined with autologous stem cell
      support or allogeneic stem cell transplantation. The clinical experience with 2
      CDA in CLL is limited, but the preliminary results suggest a similar efficacy as
      FAMP, whereas DCF seems to be less effective. The major treatment-related
      morbidity is due to myelo- and immunosuppression by long-lasting T cell
      depletion, which may facilitate a greater susceptibility of infections including
      those with opportunistic organisms as herpes simplex or herpes zoster,
      cytomegalovirus, Pneumocystis carinii, mycobacteria, listeriosis, candida and
      aspergillus in pretreated patients. However, in previously untreated patients no
      increased incidence of infections has been reported compared with other
      schedules. Whether FAMP treated patients have any advantage for overall or
      progression-free survival has to be answered by ongoing randomized trials.
      Presently, the position of FAMP and 2-CDA as two extremely active single agents
      in CLL is that of second-line therapy. Their appropriate indication in the first
      line strategy of CLL has, however, still to be defined by clinical studies in
      progress.

PMID- 9178836
TI  - Is there a place for 2-CDA in the treatment of B-CLL?
AB  - There is no doubt about 2-CDA being a very potent lymphotoxic agent that displays
      high efficacy in the treatment of CLL. It interferes with the intranuclear
      machinery of DNA regulation, and causes death to proliferative active, as well as
      resting lymphocytes. Interruption of crucial pathways that are evident for cell
      survival translates into high clinical response rates in CLL. CR and PR rates
      comparable to those reported on fludarabine are achieved in relapsed or
      refractory CLL. Even though trials on previously untreated CLL are still ongoing,
      a consistent trend towards durable, high CR rates becomes apparent. The toxicity
      is comparable to that of fludarabine and consists of infections, as well as
      thrombocytopenia. Clinical as well as in vitro studies suggest a crossresistance
      between the two purine analogues, indicating that sequential treatment is not
      useful. Given these data, although preliminary in case of de novo CLL, 2-CDA has
      to be recognized as one of the most effective cytostatic drugs currently
      available for CLL treatment. Large prospective trials (in comparison with
      fludarabine) will assess the role of 2-CDA as standard treatment. Such trials
      should also have the aim to substantiate the potential of 2-CDA as induction
      treatment followed by high-dose consolidation.

PMID- 9178837
TI  - Prophylactic strategies to meet infectious complications in fludarabine-treated
      CLL.
AB  - Fludarabine has emerged as salvage therapy in chlorambucil-resistant CLL.
      However, encouraging response rates have been compromised by a high incidence of
      serious infectious complications. Prophylactic measures to reduce the frequency
      of infections are needed, but up to now, there are no established standards for
      supportive therapy in fludarabine-treated CLL. Clinicians have observed an
      increasing frequency of life-threatening opportunistic infections but only some
      of these may be explained by fludarabine-induced impairment of cell-mediated
      immunity. Neutrocytopenia commonly found during initial fludarabine treatment may
      not have been addressed sufficiently as risk factor for infections. Thus, G-CSF
      supplementation may improve the rate of infectious complications by reducing the
      duration of fludarabine-induced neutrocytopenia. The changing spectrum of
      infectious complications should stimulate additional trials on the value of IVIG
      replacement in fludarabine-treated CLL patients and on the role of low-dose co
      trimoxazole in patients at high risk of Pneumocystis carinii infections.

PMID- 9178838
TI  - The role of stem cell transplantation in the treatment of chronic lymphocytic
      leukemia.
AB  - Stem cell transplantation (SCT) is increasingly being used for treatment of
      chronic lymphocytic leukemia (CLL). The present article summarizes available
      clinical results and discusses important aspects of SCT in patients with CLL
      including the preferable type of SCT (allogeneic vs autologous), timing of SCT,
      high-dose regimens, purging, and molecular monitoring of residual disease.

PMID- 9178839
TI  - Chronic lymphatic leukemias of T and NK cell type.
AB  - T cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL) and large
      granular lymphocyte leukemia of T or NK cell type (T-LGL or NK-LGL leukemia) are
      chronic lymphoproliferative diseases derived from post-thymic immunocompetent
      lymphoid cells. T-PLL is morphologically characterized by a prominent central
      nucleolus in a medium-sized cell expressing a mature T cell immunophenotype.
      Clonal genetic changes involving chromosome 14 and T cell receptor gene
      rearrangements are characteristics of these diseases. They are usually
      progressive and there is no efficient treatment available. The classification of
      some cases presenting with a morphological picture similar to B-CLL, but with
      immunophenotypic and clinical features resembling T-PLL, as T-CLL is still
      controversial. The phenotypic profiles and the establishment of clonality are the
      hallmarks of defining T-LGL leukemia and NK-LGL leukemia. The CD3+/CD57+/CD56-
      immunophenotype and the clonal rearrangement of the T cell receptor genes
      characterize T-LGL leukemia, which presents clinically with a rather indolent
      course of disease, complicated by frequent infections secondary to neutropenia.
      NK-LGL leukemia cells express CD3-/CD56+/CD57-, but in most cases clonality
      cannot easily be established. Clinically the patient may either present with
      constitutional symptoms and suffer a short and aggressive course of disease or
      may have a more chronic disease similar to T-LGL leukemia. Therefore, it may be
      reasonable to subdivide NK-LGL proliferation into the more aggressive 'NK-LGL
      leukemia/lymphoma' and 'chronic NK cell lymphocytosis'.

PMID- 9178840
TI  - Gastrointestinal involvement in patients with chronic lymphocytic leukemia.
AB  - Of 30 patients with CLL examined with gastroscopy and 18 with additional
      coloscopy two showed lymphocytic infiltration of the stomach as well as of the
      large intestine, one of the stomach, and two of the large intestine only. The
      lymphocytic infiltration seems to depend more on tumor burden and proliferation
      activity than on stage. These results also make evident that conventional staging
      according to Rai or Binet without current diagnostic methods does not reflect the
      real extent of disease. However, it remains open to decide which patients are
      candidates for an endoscopic investigation and whether the proof of a
      gastrointestinal involvement results in a particular therapeutic consequence.

PMID- 9178841
TI  - Outcome of patients with low-grade B cell non-Hodgkin lymphoma and initial bone
      marrow involvement: data of a single institution.
AB  - We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according
      to criteria of the Kiel classification and presenting with initial bone marrow
      involvement. Therapeutic approaches were not changed during the observation
      period 1975-1995. CLL (n=895) and IC (n=169) were treated palliatively with
      chlorambucil/prednisone or prednimustine. In CBCC (n=65) and CC (n=50) remission
      was induced with COP or CHOP. The overall response rate was 67%, but only 35% of
      CBCC and 23% of CC patients achieved complete remission. Median survival was 64
      months in CBCC and 28 months in CC. As the median age of our patient population
      was 68 years (range: 23-93) it seems doubtful whether overall prognosis can be
      improved by aggressive therapeutic measures. One exception might be CBCC patients
      who were younger (median age 56 years) and who were usually in good general
      condition so that they might qualify for high dosage chemotherapy and stem cell
      support. Whether the prognosis of IC and CLL (median survival 74 months and 107
      months, respectively) can be improved by treatment with drugs such as purine
      analogs will depend on the long-term outcome of clinical studies.

PMID- 9178842
TI  - Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma: recent results
      and future prospects.
AB  - The availability of monoclonal antibodies with well-defined specificities to
      lymphoma-associated antigens promises to open new therapeutic opportunities in
      the treatment of patients with non-Hodgkin's lymphoma. Monoclonal antibodies
      against lineage-specific surface markers such as CD19, CD20 or CD22 have been
      generated and employed in native or modified forms in clinical phase I/II trials.
      Modified versions such as toxin-conjugated antibodies or antibodies with dual
      specificities (bispecific antibodies) were introduced to enhance the cytotoxicity
      of monoclonal antibodies since native antibodies were not able to induce long
      lasting remissions in patients with advanced disease although responses were seen
      and side-effects were usually mild. Future efforts should concentrate on patients
      with minimal residual disease employing genetically engineered antibody
      fragments.

PMID- 9178843
TI  - Mantle cell lymphoma: diagnostic criteria, clinical aspects and therapeutic
      problems.
AB  - In 1992, after a history of more than two decades a subgroup within the diffuse
      low-grade B cell lymphomas designated centrocytic lymphoma, lymphocytic lymphoma
      of intermediate differentiation or mantle zone lymphoma gained general
      acceptance, now referred to as mantle cell lymphoma. Similarities between these
      entities were emphasized by identification of rearrangement and overexpression of
      CCND1 (bcl1/PRAD1) gene in the majority of cases. Unlike in all other non
      Hodgkin's lymphomas sex distribution demonstrates a striking preponderance of
      males over females with a ratio of 3:1. Initial parameters in all published
      series are advanced disease with generalized lymphadenopathy in 90%, bone marrow
      infiltration in 60-75%, splenomegaly in 55%, hepatomegaly in 35%,
      gastrointestinal involvement in about 25% and peripheral blood lymphocytosis in
      20-30% of patients. In generalized disease, clinical course is characterized by
      continuous progression with a median survival probability of 3-4 years within
      most series. Overall response rates of 56-88% with complete remissions in the
      range of 9-58% are attainable but relapse occurs predominantly within 20 months.
      At present there is no evidence that any conventional regimen is curative.
      Prospective multicenter studies are mandatory to overcome this therapeutic
      dilemma. Patients suitable for some form of maintenance or consolidation therapy
      should initially be treated intensively by anthracycline-containing regimens.
      Whether maintenance with interferon or intermittent chemotherapy including new
      agents, like purine analogues or (un)conjugated monoclonal antibodies are able to
      influence overall survival is a matter of (ongoing) investigations. Further
      experimental approaches arise from antisense oligonucleotides or ribozymes
      blocking the overexpression of bcl-1 especially in this lymphoma entity. At
      present high-dose myeloablative consolidation radiochemotherapy followed by stem
      cell rescue in first remission seems to be the most attractive option in younger
      patients.

PMID- 9178844
TI  - Local treatment with the N-methyl-D-aspartate receptor antagonist ketamine,
      inhibit development of secondary hyperalgesia in man by a peripheral action.
AB  - Due to the recent discovery of peripheral N-methyl-D-aspartate (NMDA) (and other
      glutamate) receptors in animal studies, the NMDA receptor antagonist, ketamine
      (0.83 mg/ml, 6 ml) or saline was injected s.c. preinjury in 10 healthy
      volunteers, to study the effect on burn-induced primary and secondary
      hyperalgesia. On the saline treated leg, all subjects developed primary
      hyperalgesia and secondary hyperalgesia. On the contralateral leg treated with
      ketamine, there was a significant reduction of primary hyperalgesia and an
      inhibition of development of secondary hyperalgesia. In an experimental day 2,
      lidocaine temporarily blocked the development of primary and secondary
      hyperalgesia. When saline was injected in the contralateral leg treated with
      ketamine 1 week previously (n = 6), no zone of secondary hyperalgesia was
      developed. In contrast, subjects (n = 3) treated with ketamine 2 weeks before,
      reported development of secondary hyperalgesia following saline, a preliminary
      indication of a long-lasting peripheral action of ketamine.

PMID- 9178845
TI  - NMDA and non-NMDA receptors are co-localized at excitatory synapses of rat
      hypoglossal motoneurons.
AB  - We used whole-cell patch clamp recordings in a rat brainstem slice preparation to
      characterize the properties of miniature excitatory postsynaptic currents
      (mEPSCs) in hypoglossal motoneurons. The distinct kinetic characteristics of N
      methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated synaptic responses
      allowed us to study dual component mEPSCs mediated by the two receptor types.
      Using this approach, NMDA and non-NMDA receptors were found to be co-localized at
      the same synaptic locations. In addition, some sites contain only NMDA receptors
      since a large proportion of mEPSCs were apparently mediated by NMDA receptors
      only. Furthermore, the amplitudes of pharmacologically isolated NMDA receptor
      mediated mEPSCs were highly variable in individual cells and their decay kinetics
      were modulated by membrane potential.

PMID- 9178846
TI  - Quantitative comparison of mu opioid receptor mRNA in selected CNS regions of
      alcohol naive rats selectively bred for high and low alcohol drinking.
AB  - We combined solution hybridization, ribonuclease protection and microdissection
      techniques to quantitatively compare the anatomical distribution of mu receptor
      mRNA in discrete brain regions of alcohol naive rats selectively bred for high
      and low alcohol drinking (HAD and LAD lines, respectively). The solution
      hybridization assay is highly sensitive and can detect mu opioid receptor mRNA in
      a 100-fold linear range from 4 to 421 amol. HAD and LAD rats exhibited a similar
      level of mu receptor mRNA in all central nervous system (CNS) regions examined
      except for the inferior colliculus. Our data suggest that the steady-state level
      of mu receptor mRNA is not associated with genetic differences in alcohol
      drinking behavior.

PMID- 9178847
TI  - Anticonvulsant doses of carbamazepine increase hippocampal extracellular
      serotonin in genetically epilepsy-prone rats: dose response relationships.
AB  - The antiepileptic drug carbamazepine produces dose related anticonvulsant effects
      in genetically epilepsy-prone rats (GEPRs) and most other animal seizure models.
      Carbamazepine releases serotonin as part of the pharmacodynamic action by which
      it suppresses convulsions in GEPRs and it releases serotonin in non-epileptic
      Sprague-Dawley rats. The two strains which make up the GEPR seizure model
      (moderate seizure GEPR-3s and severe seizure GEPR-9s) experience anticonvulsant
      effects in response to different doses of carbamazepine (GEPR-3 ED50 = 25 mg/kg;
      GEPR-9 ED50 = 3 mg/kg). The present study determined that carbamazepine produces
      a dose related increase in extracellular serotonin in each of the two GEPR
      strains. The doses of carbamazepine required to increase extracellular serotonin
      are similar to the doses required for an anticonvulsant effect in each of the
      strains. This result provides further support for the hypothesis that release of
      serotonin by carbamazepine is an important part of the pharmacodynamic action by
      which this drug suppresses seizures.

PMID- 9178848
TI  - Effect of interhemispheric sections of the hypothalamus on milk-ejection bursts
      of supraoptic oxytocin neurones during bilateral and unilateral suckling in the
      rat.
AB  - The burst activity of oxytocin neurones was recorded from the supraoptic nucleus
      of lactating rats with or without interhemispheric sectioning of the hypothalamus
      during bilateral or unilateral suckling. The results showed that extensive
      interhemispheric sectioning did not abolish the burst of oxytocin neurones during
      bilateral and contralateral suckling (100% of 25 neurones and 95% of 20 neurones,
      respectively), but significantly reduced the number of oxytocin neurones that
      showed the burst during ipsilateral suckling (5.3% of 19 neurones). To orientate
      the crossing site of the signals for bilateral synchronization of the bursts of
      oxytocin neurones, interhemispheric sectioning of the rostral or caudal
      hypothalamus was attempted, but either sectioning partially blocked the
      occurrence of the bursts during ipsilateral suckling. These results suggest that
      there are two separate gates located on different sides of the hypothalamus and
      that the neural connections between the gates seem distributed diffusely.

PMID- 9178849
TI  - Maintenance of constant blood acetylcholine content before and after feeding in
      young chimpanzees.
AB  - We have shown that acetylcholine (ACh) is present in the blood of various species
      of mammals using a specific, sensitive radioimmunoassay. In the present study,
      the effect on blood and plasma ACh levels of feeding after overnight fasting was
      studied in one male and five female 4- to 7-year-old chimpanzees. The mean basal
      ACh concentrations of the blood and plasma were 3143 +/- 380 and 184 +/- 10 pg/ml
      (+/-SEM, n = 6), respectively. Feeding each chimpanzee 500 g boiled sweet
      potatoes as breakfast at 1000 h and tap water given ad libitum did not affect the
      ACh content of the blood and plasma, and constant values of the blood and plasma
      ACh contents were observed for 4 h after the feeding. Hematocrit and plasma
      acetylcholinesterase (AChE) activity were also insensitive to feeding. No
      correlation was observed between plasma AChE activity and either blood or plasma
      ACh content. The results of the present study indicate that the blood ACh of
      chimpanzees is distributed mainly in the blood cell fraction, and that the blood
      ACh content is not regulated directly by cholinergic nerve activity or by plasma
      AChE activity.

PMID- 9178850
TI  - Thyroid hormone metabolism in the rat brain in an animal model of 'behavioral
      dependence' on ethanol.
AB  - Thyroid hormone metabolism was investigated in the frontal cortex and amygdala in
      groups of rats either 'behaviorally dependent' on ethanol or chronically exposed
      to ethanol, but not 'dependent'. The activities of the 5'II deiodinase isoenzyme,
      which catalyzes the deiodination of thyroxine (T4) to the active metabolite
      triiodothyronine (T3), was elevated in the frontal cortex in both the
      'behaviorally dependent' and the 'non-dependent' rats. The activities of the 5-II
      deiodinase isoenzyme, which catalyzes the inactivation of T3 to 3,3'-T2 was,
      however, selectively inhibited in the amygdalas of the rats 'behaviorally
      dependent' on ethanol, but normal in the 'non-dependent' rats. This suggests that
      increases in intracellular concentrations of T3 in the amygdala may be
      specifically related to reward mechanisms and the development of 'behavioral
      dependence' on ethanol.

PMID- 9178851
TI  - The angiotensin AT2 receptor down-regulates neurofilament M in PC12W cells.
AB  - The angiotensin (ANG II) AT2 receptor mediates antiproliferative effects and
      induces neurite outgrowth in PC12W cells. To further investigate the molecular
      events following AT2 receptor stimulation in these cells, we determined the
      expression pattern of the middle-sized neurofilament subunit (NF-M) using Western
      and Northern blot analysis and reverse-transcription polymerase chain reaction.
      On both, the protein and the mRNA level, ANG II via AT2 receptors not only
      counteracted nerve growth factor (NGF)-mediated NF-M up-regulation but also
      reduced NF-M levels in the absence of NGF by maximally 72%. The ANG II-induced
      effects were completely abolished by pretreatment with the AT2 receptor
      antagonist, PD123177. In view of previous findings of decreased NF levels in
      regenerating neurons and in neuronal cultures undergoing apoptosis, our
      observation suggests a new role of AT2 receptors in either of these processes.

PMID- 9178852
TI  - GABAergic synapses on mu-opioid receptor-expressing neurons in the superficial
      dorsal horn: an electron microscope study in the cat spinal cord.
AB  - A double-immunocytochemical electron microscope study was performed in the cat to
      examine whether GABAergic axons might be in synaptic contact with spinal neurons
      expressing mu-opioid receptor (MOR) in laminae I and II of the spinal dorsal horn
      at the lumbar cord segments. Structures showing MOR-like immunoreactivity (-LI)
      and those showing GABA-LI were labeled, respectively, with
      diaminobenzidine/peroxidase-reaction products and immunogold particles.
      Approximately one-third of dendritic profiles with MOR-LI in laminae I and II
      were postsynaptic to axon terminals with GABA-LI; about one-fourth of somatic
      profiles with MOR-LI were also postsynaptic to axon terminals with GABA-LI. The
      results suggest that activation of MOR on postsynaptic neurons may modulate
      effects which are induced by GABA released from presynaptic neurons.

PMID- 9178853
TI  - Distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide
      (PACAP), PACAP receptor, vasoactive intestinal polypeptide (VIP), and VIP
      receptors in the rat superior cervical ganglion.
AB  - The distribution of mRNAs for pituitary adenylate cyclase-activating polypeptide
      (PACAP), PACAP receptor (PACAP-R), vasoactive intestinal polypeptide (VIP) and
      two subtypes of VIP receptors (VIP1-R and VIP2-R) was examined by in situ
      hybridization in the superior cervical ganglion (SCG) of the adult rat. PACAP-R
      mRNA was expressed intensely in virtually all principal neurons. PACAP mRNA was
      expressed in approximately half of the principal neurons, where the levels of
      expression vary extensively. Intense expression of VIP mRNA was observed only in
      a few principal neurons. Neither VIP1-R mRNA nor VIP2-R mRNA was detected in SCG
      cells. These findings suggest that PACAP, but not VIP, may function as a
      paracrine or autocrine regulatory factor through PACAP-R in the principal neurons
      of the SCG.

PMID- 9178854
TI  - Effects of hypothermia on the neuronal activity, [Ca2+]i accumulation and ATP
      levels during oxygen and/or glucose deprivation in hippocampal slices of guinea
      pigs.
AB  - The protective effects of mild hypothermia (33 and 29 degrees C) on the neuronal
      activity, intracellular Ca2+ accumulation and ATP levels during deprivation of
      oxygen and/or glucose were investigated using guinea pig hippocampal slices.
      During oxygen and glucose deprivation and oxygen deprivation only, mild
      hypothermia had only minor effects on the maintenance of neuronal activity and
      ATP levels, but it suppressed Ca2+ accumulation and drastically improved the
      reversibility of neuronal activity. During glucose deprivation only, mild
      hypothermia could maintain the neuronal activity as well as ATP levels.

PMID- 9178855
TI  - The involvement of calmodulin and Ca2+/calmodulin-dependent protein kinase II in
      the circadian rhythms controlled by the suprachiasmatic nucleus.
AB  - We investigated the involvement of calmodulin and Ca2+/calmodulin-dependent
      protein kinase II (CaMKII) in the photic entrainment of circadian rhythms using
      calmodulin inhibitors such as calmidazolium (CMZ) and trifluoperazine (TFP), and
      a CaMKII inhibitor, KN-62, in rats. Fos expression in the suprachiasmatic nucleus
      (SCN) of rats induced by photic stimulation (300 lux, 1 h) during the early
      subjective night of the rats was inhibited by treatment with CMZ (10 mg/kg i.p.)
      or TFP (20 mg/kg i.p.) 30 min before photic stimulation. With respect to the
      neuronal firing rate in the rat SCN slice, KN-62 and CMZ application during the
      early subjective night attenuated the glutamate (10 microM)-induced phase shift.
      The present results suggest that calmodulin and CaMKII are involved in the photic
      entrainment mechanism in the rodent SCN.

PMID- 9178856
TI  - Further evidence for an association between a mutation in the APP gene and Lewy
      body formation.
AB  - There have been two detailed neuropathological reports of families with a valine
      to isoleucine substitution at position 717 of the amyloid precursor protein gene.
      Surprisingly, in one of these families substantial Lewy body formation occurred
      in addition to Alzheimer's disease, prompting the speculation that such a genetic
      mutation may predispose to both Lewy body and plaque formation. This report
      describes the neuropathology of an additional family with the same genetic
      mutation. Of two affected members who have come to autopsy, one had brainstem
      Lewy bodies. Some of these Lewy bodies had peripheral halos immunoreactive for
      beta-amyloid. These findings suggest a greater than chance link between genetic
      mutations for Alzheimer's disease and Lewy body formation.

PMID- 9178857
TI  - Expression of 5-HT7 receptor mRNA in rat brain during postnatal development.
AB  - The present study is the first one to demonstrate the expression of 5-HT7
      receptor mRNA by in situ hybridization during postnatal development. No
      quantitative developmental changes in the 5-HT7 gene expression was observed in
      neocortex, pyramidal layers of CA1 and CA2, dentate gyrus, most of thalamic
      nuclei, mammillary region, superior colliculus and central gray. However, in
      retrosplenial cortex, subiculum and medial habenula an increase of labeling is
      observed between postnatal days (PN) PN15 and PN21. Striatum showed a transient
      expression during the first stages of development to be undetectable in adults.
      CA3 pyramidal cell layer, intramediodorsal thalamic nucleus and lateral habenula
      displayed a high mRNA expression at PN5 and PN8 which decreased throughout
      development but it was still present in adults. A possible non-neurotransmitter
      trophic function of 5-HT mediated through 5-HT7 receptors could be suggested.

PMID- 9178858
TI  - Effect of apamin, a selective blocker of Ca2+-activated K+-channel, on
      habituation and passive avoidance responses in rats.
AB  - The effects of apamin, a selective blocker of the small conductance K(Ca)
      channels were examined in both passive avoidance and habituation of exploratory
      activity in rats. In the two experiments, animals were subjected to two trials
      separated by a 24 h interval. Apamin was administered either before or after the
      first session (acquisition) or before the second session (restitution). In the
      passive avoidance test, apamin did not alter performance whenever the time of
      administration. In the habituation task, apamin (0.4 mg/kg) decreased activity
      (distance travelled, rearing) on the two sessions only when it was injected
      before acquisition but not when injection took place just after the acquisition
      session or before the restitution session. Taken together, these findings support
      the view that the blockade of apamin sensitive K(Ca) channels improved the
      acquisition in non-stressful task, but not in a stressful situation.

PMID- 9178859
TI  - Isolation, partial purification, and ultrastructure of taste bud cells from
      rabbit foliate papillae.
AB  - A method is described for obtaining large numbers of isolated taste bud cells
      from lingual epithelium of rabbit foliate papillae. The isolation method is based
      on isopyenic sedimentation in a Percoll gradient. The purification of taste bud
      cells was evaluated by electron microscopy and by immunohistochemistry using CK
      20 antibody. The cytology of the isolated taste bud cells remained very similar
      to in situ cells. The type III cells, which are regarded as gustatory cells,
      retained their characteristic dense-cored granules in the cytoplasm. This method
      will permit study of various parameters of taste bud cell biology.

PMID- 9178860
TI  - Expression and nocturnal increase of type II iodothyronine deiodinase mRNA in rat
      pineal gland.
AB  - It has been demonstrated that thyroxine deiodinating activity is present in rat
      pineal gland, and its activity increases significantly during the night time. We
      have studied whether mRNA for type II iodothyronine deiodinase is expressed in
      rat pineal gland and whether the nocturnal rise of pineal T4 deiodinating
      activity is due to the change in type II iodothyronine deiodinase mRNA level.
      Reverse transcription-polymerase chain reaction amplification and Northern blot
      analyses have demonstrated that type II iodothyronine deiodinase mRNA is
      expressed in rat pineal gland and its mRNA level increases markedly at midnight.
      These results suggest that the nocturnal rise in pineal T4 deiodinating activity
      is due to the change in type II iodothyronine deiodinase mRNA level.

PMID- 9178861
TI  - Association between the low density lipoprotein receptor-related protein (LRP)
      and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting
      elderly people. It usually occurs after 65 years old (late-onset AD). The
      epsilon4 allele of apolipoprotein E (APOE) gene is a risk factor which
      contributes about 50% of the genetic risk for this form of the disease. The low
      density lipoprotein receptor-related protein (LRP) is a major receptor for APOE
      which is found in the senile plaques of AD brains. This makes it a good candidate
      gene for the disease. There is a polymorphism in the region upstream of the LRP
      gene that has been associated with AD in an American population. We examined this
      polymorphism by restriction fragment length polymorphism analysis in a French
      population with sporadic late-onset AD. In the previous report, a significant
      increase of the 87 bp allele was found in the AD cases; however, in our
      population, we observed a significant decrease with this same allele of the LRP
      gene. The possible reasons for this discrepancy, linkage disequilibrium or
      statistical anomaly, are discussed.

PMID- 9178862
TI  - Evidence against a permissive role of the metabotropic glutamate receptor 1 in
      acute excitotoxicity.
AB  - Excitotoxicity has been proposed to contribute to neuronal loss in a broad
      spectrum of neurodegenerative conditions such as ischemia, hypoglycaemic coma or
      cerebral trauma. Excitotoxic neuronal injury appears to be mediated mainly by the
      over-activation of glutamate receptors, especially N-methyl-D-aspartate
      receptors, with subsequent excessive Ca2+ influx. Concurrent with the activation
      of glutamate-gated ion channels, metabotropic glutamate receptors (mGluR), which
      are G-protein coupled receptors, are also expected to be activated. Excessive
      stimulation of phospholipase C-coupled mGluR, mGluR1 and mGluRS, has been
      suggested to have neurotoxic consequences. However, the contribution of mGluR
      activation on excitotoxicity is still unclear and controversial. Here we report
      that, following ischemic and excitotoxic brain injuries, inactivation of mGluR1
      does not prevent excitotoxic neuronal damage. Given the evidence that agonists at
      this group of mGluR promoted neuronal death in cerebrocortical cultures after
      oxygen-glucose deprivation or after N-methyl-D-aspartate exposure, our findings
      suggest that mGluR-mediated excitotoxicity is unlikely associated with mGluR1 but
      rather with other PLC-coupled mGluR.

PMID- 9178863
TI  - Memory, sleep and the evolution of mechanisms of synaptic efficacy maintenance.
AB  - The origin of both sleep and memory appears to be closely associated with the
      evolution of mechanisms of enhancement and maintenance of synaptic efficacy. The
      development of activity-dependent synaptic plasticity apparently was the first
      evolutionary adaptation of nervous systems beyond a capacity to respond to
      environmental stimuli by mere reflexive actions. After the origin of activity
      dependent synaptic plasticity, whereby single activations of synapses led to
      short-term efficacy enhancement, lengthy maintenance of enhancements probably was
      achieved by repetitive activations ("dynamic stabilization"). One source of
      selective pressure for the evolutionary origin of neurons and neural circuits
      with oscillatory firing capacities may have been a need for repetitive
      spontaneous activations to maintain synaptic efficacy in circuits that were in
      infrequent use. This process is referred to as "non-utilitarian" dynamic
      stabilization. Dynamic stabilization of synapses in "simple" invertebrates occurs
      primarily through frequent use. In complex, locomoting forms, it probably occurs
      through both frequent use and non-utilitarian activations during restful waking.
      With the evolution of increasing repertories and complexities of behavioral and
      sensory capabilities--with vision usually being the vastly pre-eminent sense
      brain complexity increased markedly. Accompanying the greater complexity, needs
      for storage and maintenance of hereditary and experiential information (memories)
      increased greatly. It is suggested that these increases led to conflicts between
      sensory input processing during restful waking and concomitant non-utilitarian
      dynamic stabilization of infrequently used memory circuits. The selective
      pressure for the origin of primitive sleep may have been a resulting need to
      achieve greater depression of central processing of sensory inputs largely
      complex visual information than occurs during restful waking. The electrical
      activities of the brain during sleep (aside from those that subserve autonomic
      activities) may function largely to maintain sleep and to dynamically stabilize
      infrequently used circuitry encoding memories. Sleep may not have been the only
      evolutionary adaptation to conflicts between dynamic stabilization and sensory
      input processing. In some ectothermic vertebrates, sleep may have been postponed
      or rendered unnecessary by a more readily effected means of resolution of the
      conflicts, namely, extensive retinal processing of visual information during
      restful waking. By this means, processing of visual information in central
      regions of the brain may have been maintained at a sufficiently low level to
      allow adequate concomitant dynamic stabilization. As endothermy evolved, the
      skeletal muscle hypotonia of primitive sleep may have become insufficient to
      prevent sleep-disrupting skeletal muscle contractions during non-utilitarian
      dynamic stabilization of motor circuitry at the accompanying higher body
      temperatures and metabolic rates. Selection against such disruption during
      dynamic stabilization of motor circuitry may have led to the inhibition of
      skeletal muscle tone during a portion of primitive sleep, the portion designated
      as rapid-eye-movement sleep. Many marine mammals that are active almost
      continuously engage only in unihemispheric non-rapid-eye-movement sleep. They
      apparently do not require rapid-eye-movement sleep and accompanying non
      utilitarian dynamic stabilization of motor circuitry, because this circuitry is
      in virtually continuous use. Studies of hibernation by arctic ground squirrels
      suggest that each hour of sleep may stabilize brain synapses for as long as 4 h.
      Phasic irregularities in heart and respiratory rates during rapid-eye-movement
      sleep may be a consequence of superposition of dynamic stabilization of motor
      circuitry on the rhythmic autonomic control mechanisms. Some information encoded
      in circuitry being dynamically stabilized during sleep achieves unconscious
      awareness in authentic and var

PMID- 9178864
TI  - Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like
      striatal lesions in rats chronically treated with 3-nitropropionic acid.
AB  - Impairment in energy metabolism is thought to be involved in the aetiology of
      Huntington's disease. In line with this hypothesis, chronic systemic
      administration of the mitochondrial toxin 3-nitropropionic acid to rats and
      monkeys produces selective striatal lesions similar to Huntington's disease. The
      present study examined whether rats treated with varying regimen of 3
      nitropropionic acid could present motor abnormalities reminiscent of Huntington's
      disease symptomatology, correlated with Huntington's disease specific striatal
      symptomatology. Subacute 3-nitropropionic acid treatment (15 mg/kg per day
      intraperitoneally for 10 days) produced dramatic motor symptoms associated with
      extensive neuronal loss and gliosis in the lateral striatum as well as severe
      hippocampal degeneration in 50% of the cases. In contrast, chronic 3
      nitropropionic acid treatment (10 mg/kg per day subcutaneously for one month) led
      to more subtle excitotoxic-like lesions, selective for the dorsolateral striatum
      and more closely resembling Huntington's disease striatal pathology. Animals with
      these Huntington's disease-like lesions showed spontaneous motor symptoms
      including mild dystonia, bradykinesia and gait abnormalities, which were barely
      detectable on visual inspection but could be readily identified and quantified by
      computerized video analysis. In these chronic animals, the degree of striatal
      neuronal loss was significantly correlated with the severity of spontaneous motor
      abnormalities, as is the case in Huntington's disease. The present study
      demonstrates that chronic low-dose 3-nitropropionic acid treatment in rats
      results in a valuable model of both the histological features and motor deficits
      which occur in Huntington's disease. Despite the interanimal variability in terms
      of response to 3-nitropropionic acid treatment, this rat model may be
      particularly useful for evaluating the functional benefits of new therapeutic
      strategies for Huntington's disease, particularly those aiming to reduce the
      severity of motor symptoms.

PMID- 9178865
TI  - Extensive migration and target innervation by striatal precursors after grafting
      into the neonatal striatum.
AB  - Embryonic striatal precursors grafted into the lesioned adult host striatum show
      limited integration with little migration and restricted efferent projections. In
      the present study, the influence of an immature striatal environment on the
      integrative capacity of grafted neuroblasts was examined after transplantation of
      striatal progenitors into the striatum at different stages of postnatal
      development. Mouse progenitors, derived from embryonic day 13.5-14 lateral or
      medial ganglionic eminence or the cerebellar primordium, were transplanted as a
      single cell suspension into the developing postnatal day 1, 7 and 21 rat
      striatum. The grafted cells and their axonal projections were visualized using
      antibodies raised against the mouse-specific neural markers, M6 and M2. Cells
      from the lateral (but not the medial) ganglionic eminence showed a remarkable
      capacity to innervate selectively the striatal target structures, globus
      pallidus, entopeduncular nucleus and substantia nigra, reminiscent of endogenous
      striatal neurons, which is not observed after grafting into adult hosts. M6 and
      M2-immunopositive cellular profiles from both the lateral and medial ganglionic
      eminences were observed to have migrated extensively away from the injection
      site, in contrast to the cerebellar precursors which remained clustered at the
      implantation site. Cells from the lateral ganglionic eminence were largely
      confined within the striatal complex where they developed striatal
      characteristics, displaying expression of DARPP-32, the 32,000 mol. wt dopamine-
      and cyclic AMP-regulated phosphoprotein, whereas cells from the medial ganglionic
      eminence had migrated caudally along the internal capsule and were observed
      predominantly in the globus pallidus and thalamus, in addition to the striatum.
      The cells located outside the striatum were all DARPP-32 negative. The improved
      integration and increased projection capacity of the lateral ganglionic eminence
      precursors grafted into postnatal day 1 hosts gradually declined as the host
      advanced into later stages of development (postnatal day 7), and in postnatal day
      21 hosts the grafted striatal precursors behaved similarly to grafts implanted
      into adult recipients. These results demonstrate the specific capacity of
      embryonic striatal progenitors to integrate into the developing basal ganglia
      circuitry during early postnatal development, and that the extent of neuronal and
      glial integration and graft host connectivity declines when the host has
      developed beyond the first postnatal week.

PMID- 9178866
TI  - Apomorphine priming alters the response of striatal outflow pathways to D2
      agonist stimulation in 6-hydroxydopamine-lesioned rats.
AB  - Chronic treatment with dopaminergic agonists is associated with response
      fluctuations to L-dihydroxyphenylalanine in Parkinson's disease and enhanced
      motor activity to D1 and D2 dopamine agonists in rats with 6-hydroxydopamine
      lesions of the nigrostriatal pathway. In dopamine-depleted rodents this
      phenomenon has been referred to as "priming" or reverse tolerance. The
      neurochemical changes that underlie "priming" of dopaminergic agonist responses
      are poorly understood. Some aspects of priming of D1 agonist-mediated rotation in
      the 6-hydroxydopamine-lesioned rat have been characterized, but priming of D2
      agonist-dependent motor responses has been less thoroughly studied. In this
      study, examination of rotational behaviour and induction of Fos-like
      immunoreactivity were used to investigate changes in the striatal outflow systems
      in response to treatment with the D2 agonist quinpirole in 6-hydroxydopamine
      lesioned rats that had been primed with apomorphine. Administration of
      apomorphine (0.5 mg/kg; three injections at three to six day intervals) permitted
      an otherwise inactive dose of quinpirole (0.25 mg/kg) to produce robust
      contralateral rotation and to induce the expression of Fos in striatal neurons
      belonging to the striato-nigro-entopeduncular ("direct") pathway. The increase in
      contralateral rotation and ipsilateral striatal Fos expression following
      administration of quinpirole to apomorphine-primed rats was mediated by a D2-like
      receptor and did not appear to be due to a change in sensitivity of D2 receptors.
      Apomorphine priming also enhanced the ability of quinpirole to induce Fos
      expression in the globus pallidus, a target of the striatopallidal ("indirect")
      pathway. Western blot analysis confirmed that treatment with quinpirole induced
      the expression of c-Fos protein with no change in the expression of 35-37,000
      mol. wt Fos-related antigens in apomorphine-primed rats treated with water or
      quinpirole. Induction of Fos expression in the striatum generally results from
      blockade of D2 receptors and the striato-nigro-entopeduncular pathway
      preferentially expresses D1 receptors. Thus, the quinpirole-dependent induction
      of striatal Fos in apomorphine-primed 6-hydroxydopamine-lesioned rats represents
      a qualitative alteration in striatal outflow. These studies demonstrate that
      pretreatment of 6-hydroxydopamine-lesioned rats with apomorphine increases the
      activity of the "direct" and "indirect" striatal outflow pathways in response to
      D2 receptor stimulation. These changes have the net result of enhancing
      thalamocortical activity and likely underlie the enhanced contralateral rotation
      produced by quinpirole in apomorphine-primed rats. Changes in striatal outflow,
      particularly in the striato-nigro-entopeduncular pathway, may contribute to
      alterations in D2-dependent motor responses observed after chronic dopaminergic
      stimulation in the dopamine-depleted striatum.

PMID- 9178867
TI  - Long-term potentiation induced by single volley activation: a mechanism for
      bicuculline-induced enhancement of synaptic field potentials in the CA1
      hippocampal region.
AB  - Long-term potentiation in the CA1 region is often evaluated as the change in the
      initial slope of the field response following a single test stimulus. This change
      is thought to represent an alteration of excitatory transmission only. However,
      it has recently been reported that this initial part of the field response is
      also controlled by a picrotoxin-resistant GABA(A)ergic response since bicuculline
      (100 microM), in the presence of picrotoxin, could lead to a substantial increase
      in the field response initial slope. A disinhibition may then be an important
      factor underlying expression of what is believed to be long-term potentiation of
      excitatory synaptic transmission. Alternatively, the bicuculline-induced field
      response enhancement could be due to an induction of long-term potentiation
      favoured by the low magnesium (1.25 mM) and high calcium (4 mM) concentrations
      used in these experiments. Results presented here show that neither picrotoxin
      (100 microM), nor bicuculline (100 microM), produce any significant change in
      field response initial slope, when examined using 4 mM magnesium and calcium in
      the perfusion fluid. In experiments using lower magnesium (1-1.5 mM), the same
      result was observed in most cases. In some cases, the field response following
      single test stimuli became temporally paired with spontaneous bursts of spike
      activity, and its initial slope became considerably enhanced (100%). Similar
      results could be provoked by a temporary increase in stimulus strength sufficient
      to evoke spike activity. This potentiation occluded a subsequent long-term
      potentiation induced by afferent tetanization, and it was not observed when a N
      methyl-D-aspartate receptor antagonist was present in the perfusion solution. The
      present results suggest that the bicuculline-induced enhancement of the field
      response initial slope represents an induction of long-term potentiation rather
      than being a direct consequence of pharmacological blockade of a GABA(A)ergic
      process.

PMID- 9178868
TI  - Age-dependent changes in the immunoreactivity for neurofilaments in rabbit
      hippocampus.
AB  - The distribution of the three subunits of neurofilaments was examined in the
      hippocampus of young adult rabbits (three months of age), employing a panel of
      six monoclonal antibodies. Thereafter, age-dependent and subunit-selective
      changes in neurofilament immunoreactivity in the ageing rabbit hippocampus were
      studied, using animals of one, three, six, 12, 24, 30, 36, 48, and 60 months.
      Principal cells, interneurons, axons, and various fibre systems were
      immunoreactive for all three subunits, although the localization and staining
      intensity of neurofilament immunoreactivity depended on the antibody used. Small
      cells immunopositive for the low subunit of neurofilament (presumably glial
      cells) were found abundantly in the hippocampal formation at one month, and
      (occasionally) at 30-36 months. Young rabbits (one to three months of age) had
      high numbers of interneurons stained for the high subunit of neurofilament in the
      stratum oriens/pyramidale. The number declined and plateaued to approximately 78%
      at six to 30 months, and further declined and plateaued to approximately 56% at
      36-60 months. The first decline may reflect a process of maturation, while the
      latter decline most likely relates to ageing. Ageing pyramidal cells in 48-60
      months animals revealed a slight increase for the low subunit of neurofilament,
      but no changes for the other subunits. Transient changes in neurofilament
      immunoreactivity were a striking observation in dentate gyrus granule cells
      during ageing. The staining intensity for the low subunit of neurofilament
      decreased gradually from one to 24-30 months until it was no longer detectable in
      these cells. The immunoreactivity then reappeared, most notably in granule cells
      lining the hilus, at the age of 36-48 months. By 60 months all granule cells were
      nearly immunonegative for this subunit. Axonal aberrations, immunoreactive for
      all three subunits, were found throughout the hippocampal formation. These
      aberrations first appeared in 24-month-old animals and increased in number and
      maximal size in older rabbits. The alterations in neurofilament immunoreactivity
      in the ageing hippocampus correlated with age-associated learning disabilities in
      the acquisition of a hippocampally-dependent learning task. The potential
      relevance of changes in the cytoskeletal profile of hippocampal neurons to age
      associated learning and memory disabilities is discussed.

PMID- 9178869
TI  - Effect of GABA(B) receptors on synaptic interactions in dentate gyrus granule
      neurons of the rat.
AB  - Dendritic arborization permits convergence of synaptic inputs and their
      integration in single neurons. The granule neuron in the dentate gyrus represents
      a relatively simple example where anatomically and functionally distinct medial
      and lateral perforant pathways terminate on different regions of the dendritic
      tree. High-frequency stimulation of either pathway alone results in the induction
      of long-term potentiation. However, whether the potentiated synapses in different
      parts of the dendrites interact is not known. In this study we have compared long
      term potentiation and synaptic interactions in the lateral and medial perforant
      pathways in the "disinhibited" hippocampal slice preparation in the presence of
      the GABA(A) receptor blocker bicuculline. The data show that the magnitude of
      long-term potentiation induced by tetanic stimulation was similar in both
      pathways, but differences between the two pathways were revealed after two or
      more tetanizations. A significantly smaller capacity for further long-term
      potentiation in the lateral, as compared to the medial, perforant pathway was
      found and can be attributed to stronger postsynaptic GABA(B) inhibition in distal
      dendrites of granule neurons. Blockade of GABA(B) inhibition with CGP36742 (100
      microM) unmasked additional long-term potentiation in the lateral pathway.
      Presynaptically, GABA(B) receptors produced a short-lasting heterosynaptic
      depression in the medial pathway, which was reduced by CGP36742. Coincident
      activation of the two pathways boosted long-term potentiation only in the medial
      pathway. We propose that the interactions between the two pathways are
      orchestrated to maximize associative long-term potentiation in the medial
      pathway; this may be important for types of learning attributed to the
      hippocampus.

PMID- 9178870
TI  - Characterization of neuropeptide Y receptor subtypes in the normal human brain,
      including the hypothalamus.
AB  - The aim of the present study was to investigate the existence and distribution of
      neuropeptide Y receptor subtypes in various regions of the normal human brain
      using the peptide YY derivative receptor probes, [125I][Leu31,Pro34]polypeptide
      YY/Y1 and [125I]polypeptide YY(3-36)/Y2, in addition to the non-selective ligand
      [125I]polypeptide YY. Membrane binding assays performed with post mortem frontal
      cortex homogenates revealed that [125I]polypeptide YY and [125I]polypeptide YY(3
      36) bound in a time- and protein concentration-dependent manner. Very low amounts
      of specific [125I][Leu31,Pro34]polypeptide YY binding could be detected even in
      the presence of high amounts of protein, contrasting with results obtained with
      [125I]polypeptide YY and [125I]polypeptide YY(3-36), a preferential Y2 receptor
      probe. Analysis of saturation isotherms revealed that [125I]polypeptide YY(3-36)
      bound to a single class of high-affinity sites (0.5-2 nM). Significantly higher
      binding capacities were evident for [125I]polypeptide YY(3-36) as compared to
      [125I][Leu31,Pro34]polypeptide YY, suggesting that the human frontal cortex, in
      contrast to the rat, is mostly enriched with Y2 receptors. Ligand selectivity
      profile confirmed the hypothesis that polypeptide YY(3-36), neuropeptide Y and
      polypeptide YY but not the [Leu31,Pro34] derivatives are potent competitors of
      [125I]polypeptide YY and [125I]polypeptide YY(3-36) binding sites.
      Autoradiographic studies demonstrated further that cortical areas, as well as
      most other regions of the human brain, are particularly enriched with
      Y2/[125I]polypeptide YY(3-36) sites, while only low to very low amounts of Y1
      binding were detected except in the dentate gyrus of the hippocampal formation.
      In the human hypothalamus, a preponderance of Y2 binding sites was also noted.
      Taken together, these results clearly establish that the distribution of the Y1
      and Y2 receptor subtypes in human is different from the rodent brain, the Y2
      subtype being most abundant in the human brain.

PMID- 9178871
TI  - Nitric oxide depolarizes type II paraventricular nucleus neurons in vitro.
AB  - Nitric oxide is a labile gas which has been implicated in neuronal signalling.
      The enzyme responsible for the production of this molecule is present in the
      paraventricular nucleus of the hypothalamus, yet a specific role for nitric oxide
      in neurotransmission within this nucleus remains unclear. Using whole-cell patch
      clamp recordings from paraventricular nucleus neurons in a coronal hypothalamic
      slice, we have assessed the acute effects of nitric oxide on membrane potential
      and ionic conductance. Recordings were obtained from 78 neurons with a mean
      resting membrane potential of -57.8 +/- 0.6 mV and a mean input resistance of 972
      +/- 146 M omega. Cells were electrophysiologically classified into Type I or Type
      II according to previously established criteria. Bath application of nitric oxide
      (delivered either as a gas dissolved in solution, or liberated from the donor
      compound, N-acetyl-S-nitroso-D-penicillamine) elicited reversible membrane
      depolarizations (3 mV) in 14 of the 19 Type II cells tested. These cells also
      exhibited a decrease in input resistance following nitric oxide application.
      Similar effects were observed in response to bath application of L-arginine, with
      11 of 14 cells displaying depolarizations and accompanying decreases in input
      resistance. Inhibition of nitric oxide synthase abolished the responses to L
      arginine (n=2). The nitric oxide effects persisted when voltage-activated Na+
      channels were blocked by tetrodotoxin (n=6). The depolarizations observed in Type
      II cells were mimicked by bath application of a membrane permeable cyclic GMP
      analogue (8-bromo-cyclic GMP) (n=8). Furthermore, nitric oxide depolarizations
      were abolished by pre-treatment of the slice with the guanylate cyclase
      inhibitor, LY83583 (n=4). Type I cells did not depolarize in response to nitric
      oxide (n=11). It is concluded that nitric oxide specifically depolarizes
      parvocellular neurons within the paraventricular nucleus via a mechanism that
      requires activation of guanylate cyclase and subsequent production of cyclic GMP.
      These findings provide the first insight into the cellular mechanisms underlying
      the acute effects of nitric oxide on neurons in the paraventricular nucleus.

PMID- 9178872
TI  - Single-unit responses of serotonergic dorsal raphe neurons to specific motor
      challenges in freely moving cats.
AB  - Serotonin has been hypothesized to play an important role in the central control
      of motor function. Consistent with this hypothesis, virtually all serotonergic
      neurons within the medullary nuclei raphe obscurus and raphe pallidus in cats are
      activated in response to specific motor challenges. To determine whether the
      response profile of serotonergic neurons in the midbrain is similar to that
      observed in the medulla, the single-unit activity of serotonergic dorsal raphe
      nucleus cells was studied during three specific motor activities: treadmill
      induced locomotion, hypercarbia-induced ventilatory response and spontaneous
      feeding. In contrast to the results obtained for medullary raphe cells, none of
      the serotonergic dorsal raphe cells studied (n=26) demonstrated increased firing
      during treadmill-induced locomotion. A subset of serotonergic dorsal raphe cells
      (8/36) responded to the hypercarbic ventilatory challenge with increased firing
      rates that were directly related to the fraction of inspired carbon dioxide, and
      a non-overlapping subset of cells (6/31) was activated during feeding. All
      feeding-on cells demonstrated a rapid activation and de-activation coincident
      with feeding onset and offset, respectively. Although the proportions of
      serotonergic cells activated by hypercarbia or feeding in the dorsal raphe
      nucleus were similar to those found in the medullary raphe, there were several
      major distinctions in the response characteristics for the two cell groups. In
      contrast to the medullary serotonergic neurons, only a minority of dorsal raphe
      nucleus serotonergic neurons responded to a motor challenge. Overall, the above
      results suggest very different roles for the midbrain and medullary serotonergic
      neurons in response to motor activities.

PMID- 9178873
TI  - Effects of acute, chronic ethanol and withdrawal on dorsal raphe neurons:
      electrophysiological studies.
AB  - The effect of a single intravenous administration of ethanol (0.25-1.0 g/kg) on
      the spontaneous activity of putative serotonin neurons of the dorsal raphe
      nucleus was studied in unanesthetized rats. Ethanol produced a slight but
      progressive decline in neuronal activity in 67% (six of nine) of all neurons
      tested. The remaining 33% (three of nine) were unresponsive. Upon withdrawal of
      chronic ethanol treatment (1-5 g/kg every 6 h for six consecutive days, 12 h from
      last ethanol administration), the mean firine rate of dorsal raphe neurons was
      found to be significantly reduced, by about 30% (n=71), as compared with the
      control group (n=83), whereas the cells/track index was unaltered. Under these
      conditions, ethanol administration further reduced firing rate in 67% (four of
      six) of all the neurons tested. In the remaining 33% (two of six), no response
      was observed. At 72 h after the last ethanol administration, the mean firing rate
      of dorsal raphe neurons was found to be within control values (n=90). Further, to
      evaluate the functional status of the autoreceptors under control conditions and
      after withdrawal from chronic ethanol, the selective serotonin-1A receptor
      agonist 8-hydroxy-(2-di-n-propylamino)tetralin was administered intravenously in
      cumulative doses (1-16 microg/kg) and dose-response curves were generated for
      both groups. Autoreceptor sensitivity of dorsal raphe neurons was found to be not
      statistically different in control and ethanol withdrawn rats (n=6 for both
      groups) as indexed by a similar potency displayed by 8-hydroxy-(2-di-n
      propylamino)tetralin in reducing the spontaneous activity of dorsal raphe
      neurons. The results indicate that, in spite of the widespread use of serotonin
      transmission potentiating agents in the treatment of alcoholism, neither acute
      nor withdrawal from chronic ethanol administration produces drastic effects on
      dorsal raphe neurons. However, the inhibition of dorsal raphe neuronal activity
      after acute ethanol may be due to the reported ability of ethanol to increase
      serotonin release from terminal areas. This increased serotonin tone could, at
      the level of recurrent axon collaterals in the dorsal raphe nucleus, reduce the
      spontaneous activity of the cells. On the other hand, a similar reduction in
      spontaneous activity after withdrawal from ethanol correlates well with the
      reduction in serotonin levels observed under these conditions in microdialysis
      studies.

PMID- 9178874
TI  - GABA(A) receptor activation triggers a Cl- conductance increase and a K+ channel
      blockade in cerebellar granule cells.
AB  - GABA(A) receptor activation in cerebellar granule cells induced a complex
      physiological response, namely the activation of a Cl- conductance in concert
      with a blockade of the resting K+ outward conductance (by 71% as compared to
      controls). Both responses were mediated by the activation of GABA(A) receptors,
      since they were both mimicked by the GABA(A) receptor agonist muscimol and
      antagonized by picrotoxin and bicuculline. A substantial decrease of the mean
      open time of single, outwardly rectifying K+ channels was triggered by GABA as
      revealed from cell-attached recordings; this finding implies that an
      intracellular pathway links GABA(A) receptors and K+ channels. Furthermore, this
      action of GABA is mediated through the cytoplasm, as experiments with the cell
      attached patch-clamp technique show. GABA induced a prominent membrane
      depolarization ranging from 10 to 25 mV as revealed by current-clamp recordings
      of gramicidin (or nystatin) permeabilized patches, thus selecting conditions not
      to perturb the physiological Cl- gradient across the cell. Our findings imply
      that the GABA-activated Cl- current depolarized the membrane as described for
      immature neurons. The blockade of the resting K+ channel conductance acts in
      concert and both mechanisms lead to this substantial depolarizing event.

PMID- 9178876
TI  - Dopaminergic modulation of mitral cell activity in the frog olfactory bulb: a
      combined radioligand binding-electrophysiological study.
AB  - Dopamine content in the amphibian olfactory bulb is supplied by interneurons
      scattered among mitral cells in the external plexiform/mitral cell layer. In
      mammals, dopamine has been found to be involved in various aspects of bulbar
      information processing by influencing mitral cell odour responsiveness. Dopamine
      action in the bulb depends directly on the localization of its receptor targets,
      found to be mainly of the D2 type in mammals. The present study assessed, in the
      frog, both the anatomical localization of D2-like, radioligand-labelled receptors
      of dopamine and the in vivo action of dopamine on unitary mitral cell activity in
      response to odours delivered over a wide range of concentrations. The
      [125I]iodosulpride-labelled D2 binding sites were visualized on frozen sagittal
      sections of frog brains by film radioautography. The sites were found to be
      restricted to the external plexiform/mitral cell layer; other layers of the
      olfactory bulb were devoid of specific labelling. Electrophysiological recordings
      of mitral unit activity revealed that dopamine or its agonist apomorphine induced
      a drastic reduction of spontaneous firing rate of mitral cells in most cases
      without altering odour intensity coding properties of these cells. Moreover, pre
      treatment with the D2 antagonist eticlopride blocked the dopamine-induced
      reduction of mitral cell spontaneous activity. In the frog olfactory bulb, both
      anatomical localization of D2-like receptors and functional data on dopamine
      involvement in information processing differ from those reported in mammals. This
      suggests a phylogenetic evolution of dopamine action in the olfactory bulb. In
      the frog, anatomical data perfectly corroborate electrophysiological results,
      together strongly suggesting a direct action of dopamine on mitral cells. In a
      physiologically operating system, such an action would result in a global
      improvement of signal-to-noise ratio.

PMID- 9178875
TI  - Agrin gene expression in mouse somatosensory cortical neurons during development
      in vivo and in cell culture.
AB  - Agrin is an extracellular matrix protein involved in the formation of the
      postsynaptic apparatus of the neuromuscular junction. In addition to spinal motor
      neurons, agrin is expressed by many other neuronal populations throughout the
      nervous system. Agrin's role outside of the neuromuscular junction, however, is
      poorly understood. Here we use the polymerase chain reaction to examine
      expression and alternative splicing of agrin in mouse somatosensory cortex during
      early postnatal development in vivo and in dissociated cell culture. Peak levels
      of agrin gene expression in developing cortex coincide with ingrowth of thalamic
      afferent fibres and formation of thalamocortical and intracortical synapses.
      Analysis of alternatively spliced agrin messenger RNA variants shows that greater
      than 95% of all agrin in developing and adult somatosensory cortex originates in
      neurons, including isoforms that have little or no activity in acetylcholine
      receptor aggregation assays. The levels of expression of "active" and "inactive"
      isoforms, however, are regulated during development. A similar pattern of agrin
      gene expression is also observed during a period when new synapses are being
      formed between somatosensory neurons growing in dissociated cell culture. Changes
      in agrin gene expression, observed both in vivo and in vitro, are consistent with
      a role for agrin in synapse formation in the central nervous system.

PMID- 9178877
TI  - Embryonic expression pattern of H218, a G-protein coupled receptor homolog,
      suggests roles in early mammalian nervous system development.
AB  - Heterologous expression studies employing mammalian cell tissue culture
      techniques and in vivo studies of lower eukaryotes suggest that G-protein coupled
      receptors may play critical roles in regulating early stages of vertebrate
      nervous system development. Previous work suggests that H218, a rat G-protein
      coupled receptor homolog, could serve such a role. Most importantly, northern
      blot data indicate that whole brain H218 mRNA levels are highest during
      embryogenesis. In the present studies we raised, affinity-purified and
      characterized several anti-H218, polyclonal antisera and immunohistochemically
      mapped the expression of H218 during the early stages of rat embryonic nervous
      system development. The resulting data indicate that H218 is preferentially
      expressed in young, differentiating neuronal cell bodies and axons. Moreover, the
      expression is temporally regulated such that highest H218 levels are found in
      neuronal cell bodies during their early stages of differentiation and in axons
      during their outgrowth. Therefore, we propose that H218 signal transduction may
      widely participate in the regulation of some of the first steps in neuronal
      differentiation including axon outgrowth.

PMID- 9178878
TI  - Role of adenosine in behavioral state modulation: a microdialysis study in the
      freely moving cat.
AB  - There is considerable evidence to suggest that the activity of forebrain and
      mesopontine cholinergic neurons is intimately involved in electroencephalographic
      arousal. Furthermore, our previous in vitro investigation suggested that both
      cholinergic systems are under a powerful tonic inhibitory control by endogenous
      adenosine. We thus examined the in vivo effect, on electrographically defined
      behavioral states, of microdialysis perfusion of adenosine into the cholinergic
      zones of the substantia innominata of the basal forebrain and the laterodorsal
      tegmental nucleus of freely moving cats. Localized perfusion of adenosine into
      either the basal forebrain or the laterodorsal tegmental nucleus caused a marked
      alteration in sleep-wake architecture. Adenosine (300 microM) perfused into
      either the basal forebrain or laterodorsal tegmental nucleus produced a dramatic
      decrease in waking, to about 50% of the basal level. Perfusion into the basal
      forebrain resulted in a significant increase in rapid eye movement sleep, while
      slow wave sleep was unchanged. In contrast, adenosine perfusion into the
      laterodorsal tegmental nucleus produced an increase of both slow wave sleep and
      rapid eye movement sleep, the magnitude of which were proportional to the
      decrease in waking. Electroencephalographic power spectral analysis showed that
      adenosine perfusion into the basal forebrain increased the relative power in the
      delta frequency band, whereas higher frequency bands (theta, alpha, beta and
      gamma) showed a decrease. These data strongly support the hypothesis that
      adenosine might play a key role as an endogenous modulator of wakefulness and
      sleep. The decrease in wakefulness may be directly related to the inhibition of
      cholinergic neurons of the basal forebrain and the laterodorsal tegmentum. The
      increase in rapid eye movement sleep is a novel but robust effect whose origin,
      at present, is uncertain. The observation that local perfusion of adenosine into
      either the basal forebrain or the laterodorsal tegmental nucleus dramatically
      decreases wakefulness suggests that these areas might represent a major site of
      action of the xanthine stimulants (adenosine antagonists) found in coffee and
      tea.

PMID- 9178879
TI  - Nitric oxide and excitatory postsynaptic currents in immature rat sympathetic
      preganglionic neurons in vitro.
AB  - Neuronal nitric oxide synthase immunoreactivity was localized to sympathetic
      preganglionic neurons of the intermediolateral cell column and cyclic GMP
      immunoreactivity to nerve fibers projecting into the intermediolateral cell
      column of 20-25-day-old rats. Whole-cell patch-clamp recordings were made from
      sympathetic preganglionic neurons in spinal cord slices of immature rats and the
      role of nitric oxide and cyclic GMP on excitatory postsynaptic currents was
      studied. Superfusing the slices with the nitric oxide precursor L-arginine (300
      microM) increased the amplitude of evoked excitatory postsynaptic currents as
      well as the frequency of spontaneous miniature excitatory postsynaptic currents
      in some neurons from minutes to over 1 h. The nitric oxide synthase inhibitor
      N(W)-nitro-L-arginine (100 microM) and the nitric oxide scavenger hemoglobin (100
      microM) antagonized the potentiating effect of L-arginine. The nitric oxide donor
      sodium nitroprusside (100 microM) potentiated the synaptic currents in a manner
      similar to that of L-arginine and this effect was blocked by hemoglobin. The
      membrane-permeable cyclic GMP analogue dibutyryl guanosine 3',5'-cyclic
      monophosphate (350 microM), in the presence of the phosphodiesterase inhibitor 3
      isobutyl-1-methylxanthine (750 microM), potentiated the evoked excitatory
      postsynaptic currents and increased the frequency of miniature excitatory
      postsynaptic currents; these effects were not prevented by hemoglobin. The
      results indicate that nitric oxide may facilitate the release of excitatory
      transmitters, possibly through a presynaptic cyclic GMP-dependent mechanism.

PMID- 9178880
TI  - Mutual interactions of the presynaptic histamine H3 and prostaglandin EP3
      receptors on the noradrenergic terminals in the mouse brain.
AB  - We studied whether interactions between the presynaptic histamine H3 and
      prostaglandin EP3 receptors on the noradrenergic neurons of the mouse brain
      cortex occur. Cerebral cortex slices from the mouse (and, in few experiments,
      from the rat) were preincubated with [3H]noradrenaline and then superfused with a
      physiological salt solution. Tritium overflow was evoked electrically, either at
      0.3 or 3 Hz (2 min) (standard stimulation protocol) or at 100 Hz (eight pulses)
      (stimulation protocol under which almost no activation of the presynaptic alpha2
      adrenoceptors by endogenous noradrenaline occurs). In another set of experiments,
      Ca2+ ions were introduced into Ca2+-free K+-rich medium containing tetrodotoxin
      to evoke tritium overflow. The electrically-evoked tritium overflow (0.3 Hz) was
      inhibited by histamine or the H3 receptor agonist imetit, acting via H3
      receptors. and by prostaglandin E2 or the EP3 receptor agonist sulprostone,
      acting via EP3 receptors. When histamine or imetit was given first (at
      concentrations causing the maximum effect at H3 receptors), the effect of
      prostaglandin E2 on the evoked tritium overflow was attenuated by 5-10%. When
      prostaglandin E2 or sulprostone was given first (at concentrations causing the
      maximum effect at EP3 receptors), the effect of histamine or imetit on the evoked
      overflow was attenuated by almost 50%. The previous administration of
      prostaglandin E2 also blunted the effect of histamine on the evoked tritium
      overflow evoked at 3 Hz; the degree of attenuation was identical when the current
      strength was 25 mA or was increased to 100 or 200 mA in order to partially
      compensate for the inhibitory effect of prostaglandin E2 on the evoked overflow.
      In addition, prostaglandin E2 attenuated the effect of histamine when tritium
      overflow was evoked (i) by 100 Hz, eight pulses or (ii) by Ca2+ ions or (iii)
      when rat (instead of mouse) brain cortex slices were used. An interaction of
      prostaglandin E2 or sulprostone with the H3 receptor recognition site could be
      excluded since both prostanoids did not affect the specific binding of the H3
      agonist radioligand [3H]N(alpha)-methylhistamine to rat brain cortex membranes.
      In conclusion, mutual interactions occur between the presynaptic H3 and EP3
      receptors involved in the inhibition of noradrenaline release in the mouse brain
      cortex. Pre-activation of the H3 receptor slightly attenuates the EP3 receptor
      mediated effect whereas pre-activation of the EP3 receptor more markedly
      attenuates the H3 receptor-mediated effect. The interactions may occur between
      the receptors themselves or at a step behind the receptors (e.g., at the level of
      G proteins). The physiological significance of these interactions may be to limit
      the total extent of inhibition of noradrenaline release in a scenario under which
      both receptors are activated simultaneously.

PMID- 9178881
TI  - Regional distribution of iron, transferrin, ferritin, and oxidatively-modified
      proteins in young and aged Fischer 344 rat brains.
AB  - Iron dysregulation in the brain is thought to contribute to the oxidative damage
      seen in neurodegenerative diseases including Alzheimer's disease and Parkinson's
      disease. A role for iron in the oxidative stress thought to contribute to normal
      ageing is less certain. To better characterize the role of iron in normal ageing,
      the concentrations of iron, transferrin, ferritin, and protein carbonyl groups
      are measured in nine separate regions of Fischer 344 rats. The largest
      (approximately 30%) age-related increases in brain iron concentration are seen in
      the temporal cortex, medial septum, and cerebellum. Ferritin concentration in
      these same brain regions increases 50 to 250% with age, while protein carbonyl
      concentration is only -27 to +4%, of young rats. These results indicate that an
      increase in the major iron-binding protein ferritin compensates for any age
      related increase in iron concentration, and suggest that the increased ferritin
      is cytoprotective, serving to prevent the accumulation of protein carbonyl groups
      (a principal product of metal-catalysed oxidation of proteins).

PMID- 9178882
TI  - Sequential activation of the triple excitatory transmission to the circular
      muscle of guinea-pig colon.
AB  - The aim of this study was to resolve the temporal relationships of the triple
      excitation of the circular muscle of guinea-pig colon that occurs in response to
      activation of the intrinsic excitatory nerves by using atropine and tachykinin
      NK1 and NK2 receptor selective antagonists to define the relative contribution of
      the transmitters involved. In organ bath experiments, performed in the presence
      of blockers of inhibitory innervation, a train of electrical pulses at 5 Hz for
      300 s produced a sustained contraction of the circular muscle of guinea-pig
      colon: the sequential addition of atropine (1 microM), of the tachykinin NK1
      receptor antagonist, SR 140333 (0.3 microM) and of the tachykinin NK2 receptor
      antagonist, MEN 11420 (1 microM) produced a cumulative inhibitory effect and
      progressively delayed the onset of the contractile response to nerve stimulation.
      In the presence of peptidase inhibitors, atropine was less effective in
      inhibiting the contractile response for prolonged periods of stimulation:
      however, the pattern of inhibition of the evoked response produced by the
      sequential addition of blocker drugs was not substantially affected. The
      selective tachykinin NK3 receptor agonist, senktide, produced a concentration
      dependent contraction of guinea-pig colon. The sequential addition of atropine (1
      microM), SR 140333 (0.3 microM) and MEN 11420 (1 microM) reproduced the effect of
      the same drugs on the response to electrical nerve stimulation. The peptide
      blocker of N-type voltage-dependent calcium channels, omega-conotoxin (0.1
      microM) produced a partial inhibitory effect of the response to senktide. The
      omega-conotoxin-resistant response to 1 microM senktide was inhibited and delayed
      by the progressive application of atropine, SR 140333 and MEN 11420, similar to
      the effect observed in the absence of omega-conotoxin. In sucrose gap, single
      pulse electrical field stimulation produced a fast excitatory junction potential
      which was largely (90%) inhibited by atropine; application of a low concentration
      of the potassium channel blocker, 4-aminopyridine (30 microM), markedly enhanced
      the atropine-resistant excitatory junction potential which was abolished by the
      NK1 receptor antagonist, GR 82334. We conclude that, during prolonged electrical
      or chemical stimulation of excitatory motorneurons, there is a sequential, time
      dependent activation of the three excitatory mechanisms in the circular muscle of
      guinea-pig colon: the pattern of activation is relatively independent of the
      intensity of stimulation and/or the mechanisms of secretion of released
      transmitters. Postjunctional factors predominate in determining the relative
      contribution of the three transmitters, acetylcholine, substance P and neurokinin
      A, in producing excitation of the circular muscle.

PMID- 9178883
TI  - High intracellular calcium levels during and after electrical discharges in
      molluscan peptidergic neurons.
AB  - Intracellular calcium levels ([Ca2+]i) during and following electrical activity
      of the neuroendocrine caudodorsal cells of the pond snail (Lymnaea stagnalis)
      were measured in situ and in dissociated cells by combining electrical recordings
      and Fura-2 measurements. Caudodorsal cells are typical neuroendocrine cells that
      control egg laying via the release of a set of peptides during a stereotyped
      discharge of action potentials. Single action potentials or short trains of
      spikes in dissociated caudodorsal cells induced only small but consistent
      increases in [Ca2+]i. With longer or repeated spike trains, larger [Ca2+]i
      transients were measured, indicating accumulation of calcium. The calcium channel
      blocker Ni2+ suppressed the calcium elevation, suggesting that calcium influx
      occurred through voltage-activated calcium channels. Calcium levels in
      caudodorsal cells in situ were measured before, during and after the stereotyped
      firing pattern, a approximately 35-min discharge of regular spiking. Basal
      calcium levels in caudodorsal cells in situ were about 125 nM. During the initial
      phase of the discharge, the intracellular calcium level increased to
      approximately 250 nM. Maximal calcium levels (300-600 nM) were only reached at
      the final phase of the discharge or several minutes after the cessation of
      firing. Calcium levels remained elevated for up to 1 h after the end of the
      discharge. During this time, caudodorsal cells were characterized by very low
      excitability. We suggest that the prolonged, elevated level of calcium following
      the discharge need not be directly dependent on action potentials. The long
      lasting [Ca2+]i elevation may cause the release of neuropeptides to outlast the
      duration of electrical activity, thus uncoupling release from spiking. In
      addition, it may cause reduced excitability of neuroendocrine cells following a
      period of spiking, thereby inducing a refractory period.

PMID- 9178884
TI  - Characterization of presynaptic proteins involved in synaptic vesicle exocytosis
      in the nervous system of Torpedo marmorata.
AB  - Synaptobrevin, SNAP-25 and syntaxin (SNAP receptor proteins) are molecular
      components that play a key role in the exocytotic machinery of synaptic vesicles.
      Their presence, distribution and interactions are reported in central and
      peripheral nervous systems of the electric fish Torpedo marmorata. These three
      proteins form a protein complex in all the nervous system regions tested,
      including the electric lobe and the electric organ which is innervated by pure
      cholinergic nerve terminals. Immunoblot analysis revealed a double protein
      pattern of SNAP-25 in the anterior brain and cerebellum, although a single
      protein band corresponding to SNAP-25 was observed in the electromotor system.
      Moreover, SNAP-25 showed a differential distribution in the electromotor system.
      It was present along nerve fibres and terminals that innervated the electric
      organ but it was not detected in nerve terminals at the electric lobe.
      Immunoisolation experiments using anti-synaptobrevin antibodies showed a tissue
      specific co-existence of SNAP-25 and syntaxin with synaptobrevin in the
      immunoisolated organelles. In conclusion, the molecular components of the
      exocytotic machinery are shown to be conserved in Torpedo, although some
      differences mainly on SNAP-25, suggest a potential diversity in the regulation of
      neurosecretion.

PMID- 9178885
TI  - Control processes underlying elbow flexion movements may be independent of
      kinematic and electromyographic patterns: experimental study and modelling.
AB  - Using a non-linear dynamic model based on the lambda version of the equilibrium
      point hypothesis, we investigated the shape and duration of the control patterns
      underlying discrete elbow movements. The model incorporates neural control
      variables, time-, position- and velocity-dependent intrinsic muscle and reflex
      properties. Two control variables (R and C) specify a positional frame of
      reference for activation of flexor and extensor motoneurons. The variable R
      (reciprocal command) specifies the referent joint angle (R) at which the
      transition of net flexor to extensor active torque or vice versa can be observed
      during changes in the actual joint angle elicited by an external force. The
      variable C (coactivation command) surrounds the transition angle by an angular
      range in which flexor and extensor muscles may be simultaneously active (if C >
      0) or silent (if C < or = 0). An additional, time-dimensional control variable
      (mu command) influences the dependency of the threshold of the stretch reflex on
      movement velocity. This control variable is responsible for the reflex damping.
      Changes in the R command result in shifts in the equilibrium state of the system,
      a dynamical process leading to electromyographic modifications and movement
      production. Commands C and mu provide movement stability and effective energy
      dissipation preventing oscillations at the end of movement. A comparison of
      empirical and model data was carried out. A monotonic ramp-shaped pattern of the
      R command can account for the empirical kinematic and electromyographic patterns
      of the fastest elbow flexion movements made with or without additional inertia,
      as well as of self-paced movements. The rate of the shifts used in simulation was
      different for the three types of movements but independent of movement distance
      (20-80 degrees). This implies that, for a given type of movement, the distance is
      encoded by the duration of shift in the equilibrium state. The model also
      reproduces the kinematic and electromyographic patterns of the fastest
      uncorrected movements opposed in random trials by a high load (80-90% of the
      maximal) generated by position feedback to a torque motor. The following
      perturbation effects were simulated: a substantial decrease in the arm
      displacement (from 60-70 degrees to 5-15 degrees) and movement duration (to about
      100 ms) so that these movements ended near the peak velocity of those which were
      not perturbed; a prolongation of the first agonist electromyographic burst as
      long as the load was applied; the suppression of the antagonist burst during the
      dynamic and static phases of movements: the reappearance of the antagonist burst
      in response to unloading accompanied by a short-latency suppression of agonist
      activity. These kinematic and electromyographic features of both perturbed and
      non-perturbed movements were reproduced by using the same control patterns which
      elicited a monotonic shift in the equilibrium state of the system ending before
      the peak velocity of non-perturbed movements. Our results suggest that the neural
      control processes underlying the fastest unopposed changes in the arm position
      are completed long before the end of the movement and phasic electromyographic
      activity. Neither the timing nor the amplitude of electromyographic bursts are
      planned but rather they represent the long-lasting dynamic response of central,
      reflex and mechanical components of the system to a monotonic, short-duration
      shift in the system's equilibrium state.

PMID- 9178886
TI  - Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in
      human solid tumors and leukemias.
AB  - Two ets family members, namely erg and Fli-1 are fused with two EWS family
      members namely EWS and TLS/FUS as a result of chromosome translocation in human
      solid tumors and leukemias. EWS-erg and EWS-Fli-1, which are involved in greater
      than 95% of Ewing family of tumors, were shown to function as transcriptional
      activators. TLS/FUS-erg, which is involved in human myeloid leukemias also
      functions as a transcriptional activator. Expression of these fusion proteins
      (EWS-erg and EWS-Fli-1) are shown to be essential for maintaining the oncogenic
      and tumorigenic properties of tumor cells. Cancer is thought to be caused not
      only by uncontrolled cell proliferation but also by deregulation of programmed
      cell death. Therefore, we have studied the role of normal (Fli-1 and erg) and
      aberrant fusion proteins (EWS-erg, EWS-Fli-1 and TLS/FUS-erg) in apoptosis. We
      have found that expression of normal (Fli-1 and erg) and aberrant fusion proteins
      inhibit the apoptosis of NIH3T3 cells induced by either serum deprivation or by
      treatment with calcium ionophore. We have also observed similar suppression of
      apoptosis in Ewing's sarcoma cells expressing EWS-Fli-1 and EWS-erg proteins
      suggesting that these fusion proteins may be responsible for the decreased
      ability of these tumor cells to undergo apoptosis. Inhibition of the expression
      of these aberrant fusion proteins by antisense RNA technique resulted in
      increased susceptibility to apoptosis leading to the death of tumor cells.
      Therefore, our results suggest that one can use therapeutic agents which can down
      regulate the expression of fusion proteins in combination with chemotherapeutic
      agents as an effective treatment for these human solid tumors and leukemias.

PMID- 9178887
TI  - Frequent breakpoints in the region surrounding FRA3B in sporadic renal cell
      carcinomas.
AB  - The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is the most
      active common fragile site in the human genome. We have localized aphidicolin
      induced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B
      (Paradee et al., 1996). Sequence analysis of these regions identified two
      polymorphic microsatellite markers immediately adjacent to each of these
      breakpoint clusters. In this report we have used these two new microsatellites
      and 14 additional 3p microsatellites to analyse chromosome 3p breakage and loss
      in 94 sporadic RCC samples, including nonpapillary, papillary and oncocytomas. We
      have found heterozygous loss of 3p14 sequences in >60% of the RCC samples,
      including both clear cell and papillary renal cell carcinomas. We have found
      frequent breakage in the region immediately surrounding FRA3B, demonstrating that
      FRA3B does play a role in chromosome breakage and loss in RCC. In contrast to
      other reports, >50% of the papillary tumors also showed LOH of 3p markers. We
      also observed microsatellite instability (MIN) with most of the tested markers in
      seven of eight oncocytomas and one of 69 clear cell carcinomas. The MIN in some
      oncocytomas was of the RER+ (replication error) type I phenotype. None of the
      five 3p14.2 markers detected any homozygous deletions in tumor samples, but 69/94
      (73%) of the tumors had LOH for the region, which includes the recently
      identified FHIT gene.

PMID- 9178888
TI  - Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc
      mRNA in vitro.
AB  - We previously isolated and characterized a coding region determinant-binding
      protein (CRD-BP) that might regulate c-myc mRNA post-transcriptionally. CRD-BP
      binds specifically to the coding region of c-myc mRNA and might stabilize c-myc
      mRNA in vitro by protecting it from endonucleolytic cleavage. Since c-myc
      abundance is regulated during embryonic development and cell replication, we
      investigated whether CRD-BP is also regulated in animal tissues. We focused on
      CRD-BP expression during rat liver development and liver regeneration, because c
      myc mRNA is regulated post-transcriptionally in both cases. CRD-BP expression
      parallels c-myc expression during liver development; the protein is present in
      fetal and neonatal liver but is absent or in low abundance in adult liver. In
      contrast, the up-regulation of c-myc mRNA following partial hepatectomy is not
      accompanied by up-regulation of CRD-BP. To our knowledge, CRD-BP is the first
      example of a putative mammalian mRNA-binding protein that is abundant in a fetal
      tissue but either absent from or scarce in adult tissues. Its expression in fetal
      liver and in transformed cell lines suggests CRD-BP is an oncofetal protein.

PMID- 9178889
TI  - N-Oct 5 is generated by in vitro proteolysis of the neural POU-domain protein N
      Oct 3.
AB  - The neural POU-domain proteins N-Oct 3 and N-Oct 5 were first identified in
      electrophoretic mobility retardation assays through their ability to bind to the
      octamer sequence ATGCAAAT. These two N-Oct factors are detected in extracts from
      tumor-derived and normal neural cells. They are present differentially, however,
      in extracts from melanocytes and melanoma cells: N-Oct 3 is present in extracts
      from both melanocytes and melanoma cells, whereas N-Oct 5 is more evident in
      extracts from metastatic melanoma cells. We show here that a cDNA encoding N-Oct
      3 directs synthesis of both the N-Oct 3 and N-Oct 5 proteins and that the N-Oct 5
      protein in neural and melanoma-cell extracts is also related to N-Oct 3. N-Oct 5,
      however, is apparently not expressed in vivo: It is not detected if cells are
      rapidly lysed in SDS or if extracts are prepared with a cocktail of protease
      inhibitors that includes the serine-protease inhibitor 4-(2
      Aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF). These data suggest
      that N-Oct 5 is a specific in vitro proteolytic cleavage product of N-Oct 3 and
      is not directly related to melanocyte malignancy.

PMID- 9178890
TI  - rsc: a novel oncogene with structural and functional homology with the gene
      family of exchange factors for Ral.
AB  - A novel oncogene, rsc (rabbit squamous cell carcinoma), has been identified from
      a DMBA-induced rabbit squamous cell carcinoma using gene transfer and the nude
      mouse tumorigenesis assay. A full-length cDNA has been isolated and sequenced.
      rsc has potent tumorigenic activity in nude mice (latency <4 weeks), but does not
      induce focus formation or anchorage independent growth. The oncogene resulted
      from the fusion of rHR 23A (a rabbit homologue of yeast Rad 23) with a member of
      the ral-GDS family which we named rgr (ral-GDS related). Deletion analysis
      demonstrated that the oncogenic potential resides in the Rgr portion of the gene.
      Rgr is 40% identical overall to Ral-GDS, with identity increasing to 72% over a
      100 amino acid region of the catalytic domain. Biochemical experiments indicate
      that Rgr has GTP/GDP exchange activity for Ral, providing evidence that this
      pathway is associated with tumorigenesis. The linkage between the Ral pathway and
      tumorigenesis by a molecule in the Ral-GDS gene family (Ral-GDS being a known
      effector for Ras) will open the way for the characterization of this pathway and
      provide an important tool to understand its biological function.

PMID- 9178891
TI  - Determining mutational fingerprints at the human p53 locus with a yeast
      functional assay: a new tool for molecular epidemiology.
AB  - In order to isolate experimentally induced p53 mutations, a yeast expression
      vector harbouring a human wild-type p53 cDNA was treated in vitro with the
      antineoplastic drug chloroethyl-cyclohexyl-nitroso-urea (CCNU) and transfected
      into a yeast strain containing the ADE2 gene regulated by a p53-responsive
      promoter. p53 mutations were identified in 32 out of 39 plasmids rescued from
      independent ade- transformants. Ninety-two percent of CCNU induced mutations were
      GC-targeted single base pair substitutions, and GC > AT transitions represented
      73% of all single base pair substitutions. In 70% of the cases the mutated G was
      preceded 5' by a purine. The distribution of the mutations along the p53 cDNA was
      not random: positions 734 and 785 appeared as CCNU mutational hotspots (n=3,
      P<0.0003) and CCNU induced only GC > AT transitions at those positions. The
      features of these CCNU-induced mutations are consistent with the hypothesis that
      O6-alkylguanine is the major causative lesion. One third of the CCNU-induced
      mutants were absent from a huge collection of 4496 p53 mutations in human tumours
      and cell lines, thus demonstrating that CCNU has a mutational spectrum which is
      uniquely different from that of naturally selected mutations. This strategy
      allows direct comparison of observed natural mutation spectra with experimentally
      induced mutation spectra and opens the way to a more rigorous approach in the
      field of molecular epidemiology.

PMID- 9178893
TI  - Cyclin D2 activates Cdk2 in preference to Cdk4 in human breast epithelial cells.
AB  - To investigate the possibility of differing roles for cyclins D1 and D2 in breast
      epithelial cells, we examined the expression, cell cycle regulation and activity
      of these two G1 cyclins in both 184 normal breast epithelial cells and T-47D
      breast cancer cells. Synchronisation studies in 184 cells demonstrated that
      cyclin D1 and cyclin D2 were differentially regulated during G1, with cyclin D2
      abundance increasing by 3.7-fold but only small changes in cyclin D1 abundance
      observed. The functional consequences of increased cyclin D2 expression were
      examined in T-47D cells, which express no detectable cyclin D2. Induced
      expression of cyclin D2 resulted in increases in cyclin E expression, pRB
      phosphorylation and the percentage of cells in S-phase, while constitutive
      expression resulted in a consistent trend toward reduced dependence on serum for
      continued proliferation. Thus, cyclin D2 is a positive regulator of G1
      progression in breast cells analogous to the well-documented effects of cyclin
      D1. Indeed, equimolar concentrations of inducible cyclin D1 and D2 resulted in
      quantitatively similar cell cycle effects. Marked divergence was found, however,
      in the CDKs activated by the two cyclins in breast epithelial cells. Cyclin D2
      complexes contained a higher Cdk2/Cdk4 ratio than cyclin D1 complexes. The cyclin
      D2-associated kinase activity was largely inhibited by Cdk2-specific inhibitors
      and could phosphorylate histone H1, a substrate for Cdk2 but not for Cdk4 and
      Cdk6. Therefore, cyclin D2 preferentially activated Cdk2 in breast epithelial
      cells. In contrast, Cdk4 and Cdk6 were predominantly responsible for cyclin D1
      associated kinase activity as previously reported. Thus, although cyclins D1 and
      D2 elicited similar effects on breast epithelial cell cycle progression they
      appeared to achieve this end via activation of different CDKs. This is the first
      evidence of cyclin D2 activating Cdk2 in mammalian cells thus providing further
      evidence that D-type cyclins are not necessarily redundant.

PMID- 9178892
TI  - Max and inhibitory c-Myc mutants induce erythroid differentiation and resistance
      to apoptosis in human myeloid leukemia cells.
AB  - We have used the human leukemia cell line K562 as a model to study the role of c
      myc in differentiation and apoptosis. We have generated stable transfectants of
      K562 constitutively expressing two c-Myc inhibitory mutants: D106-143, that
      carries a deletion in the transactivation domain of the protein, and In373, that
      carries an insertion in the DNA-interacting region. We show here that In373 is
      able to compete with c-Myc for Max binding and to inhibit the transformation
      activity of c-Myc. K562 cells can differentiate towards erythroid or
      myelomonocytic lineages. K562 transfected with c-myc mutants showed a higher
      expression of erythroid differentiation markers, without any detectable effects
      in the myelomonocytic differentiation. We also transfected K562 cells with a zinc
      inducible max gene. Ectopic Max overexpression resulted in an increased erythroid
      differentiation, thus reproducing the effects of c-myc inhibitory mutants. We
      also studied the role of c-myc mutants and max in apoptosis of K562 induced by
      okadaic acid, a protein phosphatases inhibitor. The expression of D106-143 and
      In373 c-myc mutants and the overexpression of max reduced the apoptosis mediated
      by okadaic acid. The common biochemical activity of D106-143 and In373 is to bind
      Max and hence to titrate out c-Myc to form non-functional Myc/Max dimers.
      Similarly, Max overexpression would decrease the relative levels of c-Myc/Max
      with respect to Max/Max. The results support a model where a threshold of
      functional c-Myc/Max is required to maintain K562 cells in an undifferentiated
      state and to undergo drug-mediated apoptosis.

PMID- 9178894
TI  - Concomitant down-regulation of expression of integrin subunits by N-myc in human
      neuroblastoma cells: differential regulation of alpha2, alpha3 and beta1.
AB  - Amplification and over-expression of the N-myc oncogene is associated with the
      progression of neuroblastoma in children and in a nude mouse model system.
      Neuroblastoma cell lines with widely different levels of N-myc illustrate an
      inverse relationship between N-myc over-expression and reduced expression of
      several integrin extracellular matrix receptors. Transfection and over-expression
      of N-myc in a neuroblastoma cell line not normally expressing the protein
      resulted in cells that grew loosely associated with tissue culture plates; this
      correlated with reduced levels of beta1 integrin subunit. Evidence is now
      presented that alpha2 and alpha3 integrin subunit levels are also reduced in
      cells that over-express N-myc, with virtually no association of alpha2 or alpha3
      subunits with beta1. Consequently, maturation of the beta1 subunit and cell
      surface expression of the integrins are greatly reduced in N-myc-transfected
      cells. A small amount of beta1 protein does get to the cell surface, however,
      suggesting that an as yet unidentified alpha subunit is produced by the N-myc
      expressing cells. Finally, the observed reductions in integrin protein levels are
      reflections of greatly reduced levels of integrin alpha2 and alpha3 mRNAs, as
      well as a smaller reduction in beta1 mRNA (80%, 94% and 52%, respectively). Post
      transcriptional mechanisms modulating beta1 integrin levels are also operative.
      These results indicate that over-expression of N-myc from a transfected gene in a
      neuroblastoma cell line that does not normally produce the protein generates cell
      lines with many of the characteristics of naturally metastatic cells with
      amplified N-myc genes. Modulation of N-myc and integrin expressions may play a
      significant role in progression of human neuroblastoma.

PMID- 9178895
TI  - In vitro inhibition of human glioblastoma cell line invasiveness by antisense uPA
      receptor.
AB  - The cell surface urokinase-type plasminogen activator receptor (uPAR) has been
      shown to be a key molecule in regulating plasminogen-mediated extracellular
      proteolysis. To investigate the role of uPAR in invasion of brain tumors, human
      glioblastoma cell line SNB19 was stably transfected with a vector capable of
      expressing an antisense transcript complementary to the 300 base pair of the 5'
      end of the uPAR mRNA. Parental and stably transfected (vector, sense, and
      antisense) cell lines were analysed for uPAR mRNA transcript by Northern blot
      analysis, and receptor protein levels were measured by radioreceptor assays and
      Western blotting. Significant reduction of uPAR sites was observed in the
      antisense transfected cell lines. The levels of uPAR mRNA were significantly
      decreased in antisense clones compared to control, vector and sense clones. The
      invasive potential of the cell lines in vitro was measured by Matrigel invasion
      assay and migration of cells from spheroids to monolayers. The antisense
      transfected cells showed a markedly lower level of invasion and migration than
      the controls. The antisense clones were more adhesive to the ECM components
      compared to parental, vector and sense clones. All transfected (vector, sense and
      antisense) clones and parental cells produced similar levels of uPA activity
      without any significant difference however, MMP-2 activity was decreased in
      antisense clones compared to controls. These results demonstrate that uPAR
      expression is critical for the invasiveness of human gliomas and down regulation
      of uPAR expression may be a feasible approach to decrease invasiveness.

PMID- 9178896
TI  - Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de
      novo methylation with independence of p16INK4a alterations in murine primary T
      cell lymphomas.
AB  - A wide panel of murine induced T-cell lymphomas have been analysed for p16INK4a
      or p15INK4b alterations. Only one gamma-radiation-induced lymphoma showed
      p16INK4a homozygous deletion and no other intragenic mutations were found in
      these INK4 genes. However, de novo methylation of the 5' CpG islands of the
      murine p15INK4b and p16INK4a genes was found to be highly frequent. While
      p16INK4a hypermethylation was found in 36% of the neutron-radiation-induced
      lymphomas and 15% of the gamma-radiation-induced lymphomas, de novo methylation
      of p15INK4b occurs in 88% and 42% of these tumors respectively, correlating with
      deficient expression of the corresponding mRNA and allelic losses in the p15INK4b
      and p16INK4a chromosome location. These data represent, to our knowledge, the
      first report on the significant involvement of hypermethylation of these INK4
      genes in murine primary tumors. Moreover, they show the importance of allelic
      losses and CpG island methylation of p15INK4b gene inactivation and support a
      tumor suppressor role for p15INK4b in T-cell lymphomas independent of p16INK4a.

PMID- 9178897
TI  - Specific p53-DNA complexes contain an mdm2-related protein.
AB  - The mdm2 gene encodes a family of proteins, a subset of which bind p53 and
      negatively regulate its function as a transcription factor. We now show that an
      anti-mdm-2 monoclonal antibody, 2A10, recognises a protein present in rabbit
      reticulocyte lysate which binds murine p53 translated in vitro. Deletion of p53
      residues 10-35, which encompass the mdm-2 binding site, abolished binding of this
      2A10-reactive protein. Binding was also dependent upon p53 protein conformation
      and may require nascent p53 polypeptide since binding was lost following
      conformational shifting of the temperature-sensitive mutant A135V. Previous
      studies have shown that mdm-2-p53 complexes fail to exhibit detectable sequence
      specific DNA binding. However, our present results demonstrate that p53 in
      complex with an mdm-2-related protein in vitro retained sequence-specific DNA
      binding capacity. Non-transformed (but not transformed) 3T3 cells were also found
      to express a similar 2A10-reactive protein, detectable by gel shift analysis of
      cellular p53 in complex with a specific DNA target. Mdm-2 in rabbit reticulocyte
      lysate and in normal, non-transformed 3T3 cells may represent constitutively
      expressed protein. Our results raise the possibility that constitutive mdm-2 may
      enhance and/or suppress functions of p53 as yet unidentified.

PMID- 9178898
TI  - Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its
      expression in prostate cancer in comparison with other BMPRs.
AB  - Bone metastasis is a common event in prostate cancer, and it is known that some
      of the bone morphogenetic proteins (BMPs) are expressed in prostate cancer cells,
      while no study on the expression of their receptors, BMPRs, has been reported.
      Here we report cloning and sequence analysis of the human BMPR-IB cDNA. We also
      analysed the expression of transcripts of three types of the BMPR genes in human
      tissues and prostate cancer cell lines. The BMPR-IB mRNA was present in various
      organs, but the highest level was found in the prostate. Moreover, the amount of
      BMPR-IB mRNA was significantly low in prostate cancer tissues after androgen
      withdrawal and was also low in prostate cancer cell lines. RT-PCR analysis showed
      that the BMPR-IB message was upregulated by androgen stimulation in the LNCaP
      cell line which expresses the androgen receptor. By contrast, the mRNA levels of
      BMPR-IA and BMPR-II were not significantly different among non-cancerous and
      cancerous prostate tissues. It was also suggested that human BMPR-IA and BMPR-IB
      might have different biological functions in the prostate, although their
      sequences were 85.3% identical in the serine-threonine kinase domain.

PMID- 9178899
TI  - Rapid induction of B-cell lymphomas in mice carrying a human IgH/c-mycYAC.
AB  - Activation of the c-myc proto-oncogene by one of the immunoglobulin (Ig) loci
      after chromosomal translocation is a consistent feature of Burkitt's lymphoma.
      Different subtypes of this tumor vary in the molecular architecture of the
      translocation region. In most cases there are no known regulatory elements of the
      Ig locus neighboring the oncogene and this considerably obscures the mechanism of
      its deregulation. In order to assess possible oncogene activation signals, we
      produced an experimental translocation region by insertion of a c-myc gene about
      50 kb from the IgH intron enhancer in a yeast artificial chromosome (YAC)
      containing a 220 kb region of the human Ig heavy chain (IgH) locus. Single copy
      integration of this YAC into the genome of mouse embryonic stem (ES) cells was
      achieved by spheroplast fusion. Chimeric mice derived from these ES cells
      developed monoclonal B-cell lymphomas expressing surface IgM by 8-16 weeks of
      age. The IgH/c-myc translocus showed different V(h)DJ(H) rearrangement in almost
      all tumors without any alterations of the distance between c-myc and the IgH
      intron enhancer. This mouse model can be used for the in vivo analysis of c-myc
      deregulation and the tumor formation capacity of the IgH locus in aberrant
      rearrangements.

PMID- 9178900
TI  - Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase
      activities independently from cell cycle position.
AB  - The transcription factor E2F activates genes required for S phase, such as cyclin
      E and cyclin A. We show that, contrary to long term effects of E2F-1
      overexpression, short ectopic overexpression of this transcription factor in
      logarithmically growing cells does neither affect the cell cycle distribution nor
      the cell size, but heavily induces cyclin E and A expression as well as cyclin E-
      and A-dependent kinase activities. We further separated logarithmically growing
      E2F-1-overexpressing cells according to their different cell cycle phases by
      centrifugal elutriation. These experiments revealed that deregulated E2F-1
      expression triggers high levels of cyclin E and A expression and kinase
      activities in small early G1 cells, normally not exhibiting these activities.
      These effects on the regulation of cyclin E- and A-associated kinases are not
      accompanied by any detectable alteration in the rate of progression through the
      cell cycle, suggesting that these changes are independent of any mitogenic
      properties of E2F-1.

PMID- 9178901
TI  - Gli family members are differentially expressed during the mitotic phase of
      spermatogenesis.
AB  - The Gli family of DNA binding proteins has been implicated in multiple neoplasias
      and developmental abnormalities, suggesting a primary involvement in cell
      development and differentiation. However, to date their specific roles and
      mechanisms of action remain obscure, and a drawback has been the lack of a model
      system in which to study their normal function. Here we demonstrate that Gli
      family members are differentially expressed during spermatogenesis in mice.
      Specifically, Gli and Gli3 mRNAs were detected in mouse germ cells, while Gli2
      was not. Further, both Gli and Gli3 exhibited stage-dependent patterns of
      expression selectively in type A and B spermatogonia. Gli expression was somewhat
      higher in type B spermatogonia while the abundance of Gli3 transcripts was
      similar in type A and B cells. Gel-shift analyses also demonstrated the
      enrichment of DNA binding activity specific for the Gli target sequence in
      spermatogonial cells. These results indicate a selective role for Gli and Gli3
      during mitotic stages of male germ cell development. Spermatogenesis may thus
      provide a unique opportunity to identify downstream targets and explore the
      normal function of Gli family proteins.

PMID- 9178902
TI  - ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death.
AB  - The Tax protein of Human T-cell leukemia virus type 1 (HTLV-1) is important for
      the T-cell immortalizing properties of this virus in vitro and is considered to
      be responsible for the early stages of leukemogenesis in infected hosts. Tax can
      upregulate expression of TNF-alpha and TNF-beta, as well as potentiate apoptosis
      in activated T-cells and in serum starved murine fibroblasts. To examine the role
      of CD95 (APO-1/Fas) and ICE-proteases in Tax-mediated active T-cell death, Jurkat
      T cells expressing (APO(S)) or lacking (APO(R)) cell surface expression of CD95
      (APO-1/Fas) were genetically modified to express hormone-inducible HTLV-1 Tax
      constructs. Hormone-inducible action of Tax alone was sufficient to promote
      programmed cell death in CD95-expressing Jurkat T-cell clones. In contrast,
      clones lacking CD95 surface expression were resistant to the antiproliferative
      action of Tax. Both APO(S) and APO(R) clones exhibited Tax-dependent upregulation
      of CD95 ligand and TNF-alpha. Blocking experiments suggested that while the
      apoptotic action of Tax critically required ICE-protease function it was largely
      independent of cell surface interaction of CD95 ligand or TNF-alpha with their
      corresponding receptors. These observations strongly implicate ICE-proteases in
      Tax-induced T-cell death, and suggest a possible involvement of CD95 in this
      process.

PMID- 9178904
TI  - A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of
      cyclin-Cdk activity in human breast cancer cells.
AB  - In order to elucidate the biochemical mechanisms by which the universal cyclin
      kinase inhibitor p27Kip1 regulates cell cycle progression in human breast cancer
      cells, a recombinant adenovirus expressing human p27 was constructed (Adp27).
      Upon infection of human breast cancer cells MDA-MB-231 and MCF-7 with Adp27, a
      high level of p27 expression was observed, and this resulted in a marked decrease
      in the proportion of cells in S-phase. In multiple cell lines, comparison of the
      cytotoxicity of Adp27 with another adenovirus vector expressing the related
      universal cyclin kinase inhibitor WAF1/Cip1 (AdWAF1), showed Adp27 to be markedly
      more (up to 56-fold) toxic than AdWAF1. DNA histograms showed Adp27 to cause a
      G1/S arrest at lower viral doses than AdWAF1. Analysis of cyclin dependent kinase
      activity following Adp27 infections showed decreased Cdk2 and cyclin B1-Cdc2
      activity at lower viral doses when compared with AdWAF1. Adp27 is therefore
      potentially useful for studies of growth regulation and for gene therapy when
      growth inhibition is desired.

PMID- 9178903
TI  - Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through
      JAK.
AB  - Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family.
      They are reported to be activated in response to cytokines, such as IL-3 and IL
      6. Janus kinases (JAKs) are known to associate with certain cytokine receptors,
      e.g. gp130, the signal transducing subunit of IL-6 receptor, and the common beta
      chain of IL-3 receptor, which can be activated upon receptor dimerization in
      response to cytokines. Here we show the association between Jak1/Jak2 and Tec or
      Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of
      Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs
      activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine
      phosphorylation. Furthermore using a yeast two-hybrid system we have identified
      the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and
      Vav. Tec associated with Vav through its SH2 domain independently of its kinase
      activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with
      the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with
      these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI
      3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase
      links cytokine receptors to PI-3 kinase probably through JAKs.

PMID- 9178905
TI  - Basic fibroblast growth factor transcriptional autoregulation requires EGR-1.
AB  - Basic fibroblast growth factor (bFGF) is an important growth factor for
      neuroectoderm- and mesoderm-derived cells. In addition bFGF is an important
      angiogenic factor and appears to contribute to tumorigenesis. This is exemplified
      by the fact that bFGF is expressed in a large majority of human gliomas and that
      bFGF expression is critical for the growth and tumorigenesis of these cells. It
      has been shown previously that bFGF can induce its own expression through an
      increase in bFGF mRNA. In this report, we show that bFGF leads to its own
      synthesis through an autoregulated transcriptional response that requires the
      transcription factor Egr-1 (also known as Krox24, Zif268 and NGFI-A). Egr-1 binds
      to two DNA elements in the bFGF promoter and positively regulates transcription.
      Mutation of these sites blocks the ability of bFGF to transcriptionally regulate
      the bFGF promoter. These data indicate a mechanism to explain how bFGF functions
      to autoregulate its expression and demonstrate that Egr-1 is as an essential
      transcription factor in this process.

PMID- 9178906
TI  - c-myc activates RCC1 gene expression through E-box elements.
AB  - Proto-oncogene c-myc is implicated in proliferation of mammalian cells. Although
      c-Myc protein has been demonstrated to function as a transcription factor
      recognizing an E-box (CACGTG) element, few c-myc-regulated genes have been
      identified and the specific role of c-myc is still unclear. RCC1 is necessary for
      mammalian cells to proliferate. Four CACGTG elements exist within 1.3 kb
      downstream of the major transcription start site for the human RCC1 gene in HeLa
      cells. Stimulation of HeLa cells with serum increased c-myc expression and RCC1
      expression. Therefore the relationship between the expression of RCC1 and c-myc
      was investigated. Rat 3Y1 cells overexpressing c-myc contained about twice as
      much RCC1 mRNA as control cells. When a chimeric protein comprised of c-myc and
      the estrogen binding domain of estrogen receptor was activated by addition of 4
      hydroxytamoxifen (OHT), expression of RCC1 mRNA increased twofold. To examine
      whether c-Myc functions through the CACGTG elements, a DNA fragment of RCC1
      intron 4, exon 5 and part of intron 5 was joined to firefly luciferase cDNA to
      construct a reporter plasmid. In transient expression experiments using HeLa
      cells, co-transfection with c-myc stimulated the luciferase activity up to 2.5
      fold in a dose-dependent manner. When the CACGTG elements in the reporter plasmid
      were destroyed, stimulation by c-myc was not observed. The four CACGTG elements
      did not contribute equally to the stimulation by c-myc. Gel retardation
      experiments suggest that c-Myc with Max binds to the CACGTG elements in the
      context of the RCC1 gene sequence in vitro. These results indicate that c-Myc can
      regulate expression of RCC1 through the E-box elements.

PMID- 9178907
TI  - Homologous regions of Fen1 and p21Cip1 compete for binding to the same site on
      PCNA: a potential mechanism to co-ordinate DNA replication and repair.
AB  - Following genomic damage, the cessation of DNA replication is co-ordinated with
      onset of DNA repair; this co-ordination is essential to avoid mutation and
      genomic instability. To investigate these phenomena, we have analysed proteins
      that interact with PCNA, which is required for both DNA replication and repair.
      One such protein is p21Cip1, which inhibits DNA replication through its
      interaction with PCNA, while allowing repair to continue. We have identified an
      interaction between PCNA and the structure specific nuclease, Fen1, which is
      involved in DNA replication. Deletion analysis suggests that p21Cip1 and Fen1
      bind to the same region of PCNA. Within Fen1 and its homologues a small region
      (10 amino acids) is sufficient for PCNA binding, which contains an 8 amino acid
      conserved PCNA-binding motif. This motif shares critical residues with the PCNA
      binding region of p21Cip1. A PCNA binding peptide from p21Cip1 competes with Fen1
      peptides for binding to PCNA, disrupts the Fen1-PCNA complex in replicating cell
      extracts, and concomitantly inhibits DNA synthesis. Competition between
      homologous regions of Fen1 and p21Cip1 for binding to the same site on PCNA may
      provide a mechanism to co-ordinate the functions of PCNA in DNA replication and
      repair.

PMID- 9178908
TI  - Bombesin and neuromedin B stimulate the activation of p42(mapk) and p74(raf-1)
      via a protein kinase C-independent pathway in Rat-1 cells.
AB  - The mechanisms by which seven transmembrane receptors activate p42
      (mapk)/p44(mapk) are not well defined although p21ras- and protein kinase C (PKC)
      dependent pathways have been implicated, typically for Gi- and Gq-coupled
      receptors, respectively. Here, we demonstrate that in Rat-1 cells transfected
      with the Gq-coupled bombesin/gastrin releasing peptide receptor, bombesin
      stimulated activation of p42(mapk) that was not inhibited by the specific PKC
      inhibitor GF 109203X or by down regulation of phorbol ester-sensitive PKC
      isoforms. In addition, bombesin rapidly stimulated p74(raf-1) activity that was
      also independent of PKC activity and insensitive to inhibition by pertussis
      toxin. Furthermore, addition of neuromedin B to Rat-1 cells transfected with the
      neuromedin B preferring receptor also activated p42(mapk) and p74(raf-1) in a PKC
      independent and pertussis toxin-insensitive manner. Finally we show that addition
      of bombesin to Rat-1 cells stimulated the GTP loading of p21ras. Our results
      reveal a novel PKC-independent pathway in the action of Gq-coupled receptors and
      stress the importance of cell context in defining the signal transduction
      pathway(s) that link specific receptors to the activation of the mitogen
      activated protein kinase cascade.

PMID- 9178909
TI  - CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1
      receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2.
AB  - Recently c-Cbl has been reported to be phosphorylated upon CSF-1 stimulation. The
      product of the c-cbl proto-oncogene (c-Cbl) is a 120 kDa protein harboring
      several docking sites for Src homology 2 (SH2) domain containing proteins and
      proline-rich regions that have been shown to allow its constitutive association
      with the SH3 domains of Grb2. We demonstrate here that CSF-1 exposure of stable
      transfectant CHO cells expressing the CSF-1 receptor induced the sustained
      tyrosine phosphorylation of c-Cbl and its subsequent association with Crk-II and
      the p85 kDa subunit of the PI 3-kinase, while it constitutively associates with
      Grb2. We demonstrate by in vitro experiments that these associations require the
      SH2 domain of Crk-II and both the C- and N-terminal SH2 domains of the p85
      subunit of the PI 3-kinase. cCbl is the major PI 3-kinase-containing protein in c
      Fms expressing CHO cells upon CSF-1 stimulation. Thus c-Cbl behaves as a core
      protein, allowing the formation of a quaternary complex including, Crk-II, PI 3
      kinase and Grb2. We provide evidence that this multiprotein complex can interact
      with the tyrosine phosphorylated CSF-1 receptor through the unoccupied SH2 domain
      of Grb2.

PMID- 9178910
TI  - Localization of a growth suppressor activity in MCF7 breast cancer cells to
      chromosome 17q24-q25.
AB  - Chromosome 17 is one of the most frequently altered chromosomes in malignant
      breast cancer. At least four genes implicated in breast cancer reside on
      chromosome 17 (p53, 17p13; Her-2/neu/ERBB2, 17q12; BRCA1, 17q21; and nm23,
      17q22). In addition, allelic imbalance has been described for at least five
      regions of chromosome 17. We have previously shown that the introduction of a
      normal human chromosome 17 into the breast cancer cell line MCF7 by microcell
      mediated chromosome transfer (MMCT) results in the in vitro growth arrest of
      these cells within 8 weeks, suggesting the presence of a growth suppressor on
      chromosome 17. Additionally, we have shown that the tumor suppressor gene p53 is
      not responsible for this phenotype, as it is wild type in MCF7 cells, and
      overexpression has no effect on either the in vitro or in vivo growth of these
      cells. We have further localized this growth suppressor gene to 17q24-q25 by
      transfer of chromosome 17 hybrids containing defined deletions. Whereas transfer
      of hybrids that contained an intact 17q (delta43/A9 and delta26/A9) resulted in
      growth arrest, two hybrids with overlapping deletions at 17q24-q25, had no effect
      on growth of MCF7 cells. Molecular analyses revealed that 50/70 (71%) of the
      resulting delta2/MCF7 or delta624/MCF7 MMCT clones retained an intact introduced
      chromosome 17. In contrast, only 8/34 (24%) of delta43/MCF7 revertants (deleted
      for 17p13.1-pter) which escaped growth arrest showed no breakage of the
      introduced chromosome 17. We did not observe a preferential loss of an intragenic
      BRCA1 marker in the MMCT hybrids, excluding BRCA1 as the gene responsible for
      this growth arrest phenotype. These data therefore implicate a new growth
      suppressor gene involved in breast cancer that is localized to chromosome 17q24
      q25.

PMID- 9178912
TI  - Loss of heterozygosity and reduced expression of the CUTL1 gene in uterine
      leiomyomas.
AB  - Cytogenetic analyses has revealed deletions and/or rearrangments at several
      chromosomal positions in approximately half of uterine leiomyomas. The most
      frequent genetic alteration, deletion of 7q22, was found in approximately 35% of
      studied cases with cytogenetic abnormalities (128/366=35%). The same chromosomal
      band was also found to be deleted in a fraction of acute myeloid leukemias and
      myelodysplastic syndromes. The frequent deletion of 7q22 in some tumors suggest
      that a tumor suppressor gene may be located in this region. The human Cut-like
      homeobox gene, CUTL1, is one of the genes localized to 7q22 and it was shown
      previously to encode a transcriptional repressor that down-modulates the
      expression of c-Myc. Activation of the c-Myc oncogenic potential has been shown
      in many cancers to result from alterations in one or the other of its several
      mechanisms of regulation. These observations led us to hypothesize that CUTL1
      could act as a tumor suppressor gene. In the present study, we have identified
      polymorphic markers within and directly adjacent to CUTL1 at 7q22 and
      demonstrated that these markers are present in a commonly deleted region in seven
      out of 50 uterine leiomyomas samples examined. Furthermore, Northern blot
      analysis revealed that CUTL1 mRNA levels were reduced in eight tumors out of 13.
      These results suggest that CUTL1 may act as a tumor suppressor gene whose
      inactivation could be of pathological importance in the etiology of uterine
      leiomyomas.

PMID- 9178911
TI  - HPV-16 oncogenes E6 and E7 are mutagenic in normal human oral keratinocytes.
AB  - The mutation frequency of pS189 shuttle vector plasmids is higher in human oral
      keratinocytes (NHOK) immortalized with cloned human papillomavirus-16 (HPV-16)
      genome than in primary normal NHOK (NHOK). To determine whether oncoproteins E6
      and E7 of HPV-16 are responsible for the higher mutation frequency of the
      plasmids, we measured the mutation frequency in NHOK and in NHOK expressing the
      HPV-16 oncogenes (E6, E7, or E6 plus E7). We also measured the mutation frequency
      in NHOK expressing the E6 or E7 proteins of the non-oncogenic HPV-6b. The
      mutation frequency, either background or N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG)-induced, in NHOK expressing the HPV-16 oncoproteins (E6, E7, or E6 plus
      E7) was significantly higher than in NHOK. The HPV-16 oncogenes did not alter the
      nature of the MNNG-induced mutations (G:C-->A:T), but increased the frequency of
      deletions and insertions with or without MNNG. The background or MNNG-induced
      mutation frequency in NHOK expressing the HPV-6b E6 or E7 proteins was the same
      as in NHOK. NHOK and NHOK expressing HPV6b-E6 or E7 were able to arrest the cell
      cycle and enhance cellular p53, p21(WAF1/CIP1), and Gadd45 levels when exposed to
      MNNG, whereas NHOK expressing the HPV-16 E6 oncogene did not demonstrate. NHOK
      expressing HPV-16 E7 were able to enhance cellular p53, p21(WAF1/CIP1), and
      Gadd45 levels, but failed to arrest cell cycle progression when exposed to MNNG.
      These data indicate that HPV-16 E6 and E7 oncogenes are mutagenic in human oral
      keratinocytes and enhance the mutagenic effect of MNNG. However, the E6 and E7
      proteins of the 'low risk' HPV-6b did not demonstrate such an ability.

PMID- 9178914
TI  - Sleep and melatonin in infants: a preliminary study.
AB  - Sleep-wake patterns of 20 normal, healthy infants (16 girls and four boys; age
      range: 26-37 weeks) were recorded for a period of 1 week with a miniature
      activity monitor. Urine samples were extracted from the infants' disposable
      diapers that were collected during a 60-hour period to determine the levels of 6
      sulphatoxymelatonin (aMT6s, a melatonin metabolite) using a radioimmunoassay
      test. Infants with "mature" secretion patterns (i.e. with an adult-like circadian
      rhythm) had a significantly delayed sleep-wake cycle in comparison to those with
      "immature" patterns. The onset of their nocturnal-sleep episode was delayed by
      almost 1 hour (22.1 vs. 21.2 hours; p < 0.05). Higher secretion rates of aMT6s
      during the evening hours (6:00-10:00 p.m.) were associated with earlier onset of
      nocturnal sleep (r = 0.51; p < 0.05). A delayed peak of melatonin was associated
      with more fragmented sleep during the night (e.g. r = 0.49; p < 0.05; for lower
      sleep percent). These findings suggest that melatonin plays an important role in
      the evolution of the sleep-wake system.

PMID- 9178913
TI  - Bcr phosphorylated on tyrosine 177 binds Grb2.
AB  - We and others have shown that the Bcr-Abl oncoprotein binds activators of the Ras
      pathway such as Grb2 and Shc. Grb2 binding is mediated through a phosphorylated
      tyrosine residue (Y177) located within a consensus Grb2 binding site encoded by
      the first exon of the BCR gene. Our results indicate that P160 BCR is tyrosine
      phosphorylated at the same site by Bcr-Abl in kinase assays (Puil et al., 1994).
      We performed experiments to determine whether Bcr, which was tyrosine
      phosphorylated within cells by activated c-Abl, could also bind Grb2, and whether
      phosphotyrosine 177 was the major binding site. Complexes between Bcr and Abl
      were detected in a hemopoietic cell line lacking Bcr-Abl and in COS1 cells
      coexpressing both Bcr and Abl proteins. P160 BCR was tyrosine phosphorylated in
      COS1 cells coexpressing Abl and Bcr proteins. Similarly, various deletion mutants
      of Bcr including BCRN553, BCRN413 and BCRN221 were tyrosine phosphorylated by
      activated c-Abl whereas BCRN159 was not. Wild-type Bcr and Bcr Y177F were
      examined under these conditions for their ability to co-precipitate with Grb2.
      The results showed that while wild-type tyrosine phosphorylated Bcr efficiently
      bound Grb2, tyrosine phosphorylated Bcr Y177F had greatly reduced Grb2-binding
      ability. Studies with GST-SH2 (Grb2) revealed that tyrosine phosphorylated Bcr
      was able to bind to GST SH2 (Grb2) but tyrosine phosphorylated Bcr Y177F was
      deficient in binding. These results indicate that the Bcr protein when
      phosphorylated at tyrosine 177 binds Grb2, thereby implicating Bcr as a potantial
      activator of the Ras pathway.

PMID- 9178915
TI  - Longitudinal changes in diary- and laboratory-based sleep measures in healthy
      "old old" and "young old" subjects: a three-year follow-up.
AB  - We report a longitudinal study of diary- and laboratory-based sleep measures in
      50 healthy elderly subjects followed prospectively over a 3-year interval. Our
      hypothesis was that "old old" subjects (aged 75 to 87; n = 27) would show decline
      over time in measures of sleep quality, continuity, and depth, whereas "young
      old" subjects (aged 61 to 74; n = 23) were expected to show stability of outcome
      measures. Using analysis of variance-based planned contrast procedures, we found
      that this hypothesis was strongly supported for subjective sleep quality and
      laboratory measures of sleep latency, sleep efficiency, wakefulness after sleep
      onset, and slow-wave sleep percent. These changes were accompanied by increased
      napping in the old old. However, there was no change of habitual time in bed
      (total time or temporal placement of nighttime sleep), daily social rhythms, or
      sleep apnea. Change in medical burden scores did not correlate significantly with
      change in sleep efficiency or other outcome variables in the old old.
      Intervention designed to slow age-dependent decreases in sleep quality,
      continuity, and depth is discussed. The current results are representative of
      healthy elderly; sleep would probably deteriorate earlier and more quickly in
      elderly with more serious health problems and heavier medication use.

PMID- 9178916
TI  - The effects of acute exercise on sleep: a quantitative synthesis.
AB  - We used meta-analytic methods to examine the influence of acute exercise on
      sleep. Thirty-eight studies were reviewed yielding 211 effects on 401 subjects.
      Mean effect sizes were calculated for sleep onset latency (SOL), stage 2, slow
      wave sleep (SWS), rapid eye movement (REM) sleep, REM latency (REM-L), total
      sleep time (TST), and wakefulness after sleep onset (WASO). Moderating influences
      of subject fitness, heat load, exercise duration, time of day, associated light
      environment (i.e. indoor or outdoor), sleep schedule, and the scientific quality
      of the studies were examined. Effect sizes for SWS, REM, REM-L, and TST were
      moderate [0.18-0.52 standard deviation (SD)] and their associated 95% confidence
      intervals did not include zero. Exercise duration and time of day were the most
      consistent moderator variables. In contrast with previous hypotheses, heat load
      had little influence on sleep. The results of our quantitative synthesis of the
      literature are inconsistent with previous narrative reviews (1,2) which suggested
      that exercise elicits larger changes in sleep than those quantified in this meta
      analysis. A major delimitation of published studies on the effects of acute
      exercise has been an exclusive focus on good sleepers. Hence, the effects we
      report herein may be underestimates of the efficacy of exercise for enhancing
      sleep among people with sleep disturbances.

PMID- 9178917
TI  - Morning work: effects of early rising on sleep and alertness.
AB  - The aim of the present study is to investigate how early morning work affects
      sleep and alertness. Twenty-two females, employed as airline cabin crew members,
      participated in the study. The design included two sleep conditions (work day and
      free day) for an early group and for a control group. The results show that early
      morning work reduced sleep to 5 hours and 12 minutes and that the reduction of
      sleep consisted of less stage 2 and rapid eye movement (REM) sleep. However, when
      the analysis was restricted to the first 5 hours, no differences in sleep stages,
      arousals, or sleep continuity were obtained between groups or conditions.
      Analysis of electroencephalogram (EEG) power density for the 0.5-16.5 Hz bands
      across nonREM periods showed no differences. With respect to the subjective
      ratings, early morning work was associated with more apprehension of difficulties
      in awakening and insufficient sleep. Daytime alertness and ease of awakening did
      not differ between groups, but the early group had significantly more sleepiness
      and complained more of unrefreshing sleep in connection with the work day
      compared to the free day. Ratings of insufficient sleep and high daytime
      sleepiness were mainly predicted (multiple regression analyses) by short total
      sleep time (TST), whereas apprehension of an unpleasant awakening was predicted
      by an early wake-up time. It was concluded that early morning work causes a
      reduction of sleep time and an increase in apprehension stress.

PMID- 9178918
TI  - Sleep apnea, norepinephrine-release rate, and daytime hypertension.
AB  - Patients with obstructive sleep apnea (OSA) are often hypertensive, and both
      apneics and hypertensives are reported to have increased sympathetic nerve
      activity. We measured plasma norepinephrine (NE) levels, clearance, and release
      rate among 65 subjects who breathed room air, a hypoxic gas mixture, and the
      hypoxic mixture combined with intermittent breath holding. Apneics' plasma NE
      across all three breathing conditions was 307 pg/ml compared with the non
      apneics' level of 248 pg/ml (p = 0.017). NE clearance increased from 3.2 l/minute
      to 3.9 l/minute when subjects breathed a hypoxic gas mixture (p < 0.001). NE
      clearance was similar among normal controls, apneics, and hypertensives. The rate
      at which NE was released from sympathetic nerves into the bloodstream was higher
      among hypertensives but not among apneics while subjects breathed room air.
      Hypoxia increased the NE-release rate from 892 ng/minute to 1,042 ng/minute (p <
      0.001) and increased the NE-release rate more among apneics than non-apneics (p <
      0.001). The NE-release rate response to hypoxia and breath holding differed
      between hypertensives and normotensives (p < 0.001) and between apneics and non
      apneics (p < 0.001). Normotensive apneics had the largest increase in NE release
      during hypoxia. Like other investigators, we found that plasma NE levels were
      increased among apneics. Calculation of NE-release rate and correction for blood
      pressure status revealed a more complex situation. Apneics breathing room air had
      a normal NE-release rate; any increase in sympathetic neuronal NE release could
      be attributed to apneics who were also hypertensive. However, apneics had a
      greater NE response to hypoxia. These results suggest that apneics are
      susceptible to transient increases in sympathetic nervous activity and that
      hypertensive apneics maintain increased sympathetic nervous release of NE in the
      daytime.

PMID- 9178919
TI  - Using self-reported questionnaire data to prioritize OSA patients for
      polysomnography.
AB  - Many laboratories have large numbers of patients with suspected obstructive sleep
      apnea (OSA) waiting to be tested. We assessed the use of simple clinical data to
      detect those patients with an apnea index <20 (low AI) who could be studied less
      emergently. Using questionnaires completed by patients prior to evaluation, we
      collected data on 354 consecutive patients (281 males, 73 females; mean age 48.6
      years) referred for OSA and assessed with polysomnography (PSG). The
      questionnaires included the Epworth sleepiness scale (ESS), height, weight, age,
      and a history of observed apnea. Analysis of receiver operating characteristics
      curves revealed that both body mass index (BMI) [area under curve = 0.7258,
      standard error (SE) = 0.03, p < 0.01] and ESS (area under curve = 0.5581, SE =
      0.03, p = 0.03) were significantly better than chance alone in detecting people
      with AI < 20. ESS < or =12 was found in 37.9% of the subjects but 39.6% of those
      expected to have a low AI using ESS had an AI > or =20. A BMI < or =28 was found
      in 24.9% of the subjects; 14.8% of those expected to have a low AI using BMI had
      an AI > or =20. Combining these variables improved accuracy but resulted in
      smaller groups; a cut-off of ESS < or =12 and BMI < or =28 resulted in a group of
      33 (9.3% of subjects), only two (6%) of whom were falsely called low AI. Adding
      to this the fact that apnea had not been observed resulted in a group of nine
      patients (2.5% of subjects), none of whom had an AI > or =20. Thus there is a
      tradeoff; the more variables used, the greater the accuracy but the smaller the
      percent of cases selected to have low AI. However, in laboratories with hundreds
      of patients waiting to be tested, any procedure better than chance to help
      prioritize patients seems worthwhile.

PMID- 9178920
TI  - Accuracy of CPAP predicted from anthropometric and polysomnographic indices.

PMID- 9178922
TI  - Transient DNA relaxation in Escherichia coli induced by nalidixic acid.
AB  - We report here the transient relaxation of plasmid DNA by inhibitors of DNA
      gyrase in Escherichia coli. Relaxation of plasmid DNA in the presence of
      nalidixic acid, an inhibitor of the A subunit of DNA gyrase, lasted less than 60
      min. The effect of nalidixic acid was not observed in a nalA26 mutant, a strain
      resistant to nalidixic acid due to a mutation in the gyrA gene. Novobiocin, whose
      target is the B subunit of DNA gyrase, also caused transient DNA relaxation.
      Resupercoiling of relaxed DNA in the presence of nalidixic acid was inhibited by
      pretreatment of the cells with chloramphenicol. As mutations of both the rpoH and
      recA genes did not affect the resupercoiling reaction, this step seems to require
      protein synthesis that is independent of both heat shock and SOS responses.

PMID- 9178923
TI  - Primary structure of base non-specific and acid ribonuclease from bullfrog (Rana
      catesbeiana).
AB  - A base non-specific acid ribonuclease (RNase RCL2) was purified from bullfrog
      liver [H. Yagi et al. Biol. Pharm. Bull., 18, 219-222 (1992)]. The sequence study
      and comparison of the amino acid sequence of the enzyme with homologous RNases
      from oyster, drosophila and chicken liver suggested that the RNase RCL2 consisted
      of two components, large protein fraction (182 amino acid residues) and peptide 2
      (20 amino acid residues) or peptide 1 (18 amino acid residues), and that both
      components bind with disulfide bridge. The RNase preparation was probably formed
      from a single polypeptide protein by processing with some proteases. The amino
      acid sequence of RNase RCL2 showed that the RNase belongs to the RNase of RNase
      T2 family and its sequence most resembles chicken liver acid RNase. In RNase
      RCL2, the amino acid residues which consist of the active site and major base
      recognition site of RNase Rh, a typical RNase of RNase T2 family, are very well
      conserved except for Tyr57 (RNase Rh numbering), and part of the amino acid
      residues of the minor base recognition site (Phe101 and Pro92) are also
      conserved.

PMID- 9178924
TI  - Alteration of fatty acid composition in a pgsA3 mutant of Escherichia coli.
AB  - We examined the fatty acid composition in an Escherichia coli pgsA3 mutant
      lacking the potential to synthesize phosphatidylglycerolphosphate, a precursor of
      phosphatidylglycerol. The contents of C18:1cis-9 (oleic acid) and C18:1cis-11
      (cis-vaccenic acid) in the total phospholipids extracted from the pgsA3 mutant
      growing at 37 degrees C were higher and that of C14:0 was lower than the wild
      type cells, resulting in a higher level of unsaturation of fatty acids (ratio of
      unsaturated fatty acids to saturated ones) in the mutant. The higher level of the
      unsaturated fatty acids in the pgsA3 mutant was more obvious in cardiolipin than
      in phosphatidylethanolamine. On the other hand, at 28 degrees C, at which the
      pgsA3 mutant shows limited cell growth, the content of unsaturated fatty acids in
      cardiolipin decreased in the pgsA3 mutant compared with the wild type. We
      consider that the pgsA3 mutant maintains cellular homeostasis by altering the
      level of unsaturated fatty acids in cardiolipin, and the mechanism is influenced
      by temperature.

PMID- 9178925
TI  - Gastric mucin secretion from cultured rat epithelial cells.
AB  - In order to establish the measurement of gastric mucin secreted from cultured
      mucous cells, rat gastric mucin was purified from secreted mucus with Sepharose
      CL-4B column chromatography. Gastric mucin was measured by dot blot analysis
      using an enzyme-linked lectin (soybean agglutinin) assay in a good concentration
      dependent manner. Surface epithelial cells were dispersed by limited digestion of
      a rat everted stomach and collected by density gradient centrifugation with
      Percoll. These cells were inoculated onto gelled collagen dishes, then cultured
      in a medium supplemented with 10% fetal calf serum under a 5% CO2 atmosphere in
      air. Changing the medium after a 2-d culture, the cells were cultured for another
      3 d. During the culture, the numbers of cells each day were almost equal, but
      mucin contents in the cells increased, and then dropped at day 5 after
      inoculation. At that time, the edge of the cell layer peeled off and the cells
      adhered to each other. Using 2-d cultured cells, the effects of some
      secretagogues on mucin secretion were investigated. Carbachol, secretin, CCK-8
      and prostaglandin E2 (PGE2) strongly stimulated mucin secretion, and gastrin I
      weakly did. However, histamine offered no stimulation.

PMID- 9178926
TI  - Involvement of a peripheral mechanism in the emesis induced by cardiac glycosides
      in Suncus murinus.
AB  - The ability of three cardiac glycosides, ouabain, digitonin and digitoxin, to
      induce emesis and their mechanism(s) of action were investigated in Suncus
      murinus. The intraperitoneal injection of ouabain but not digitonin nor digitoxin
      caused vomiting in a dose-dependent manner. However, the administration of
      ouabain into the cerebroventricle did not cause emesis. Ouabain-induced emesis
      was partly prevented by surgical abdominal vagotomy. Pretreatment with
      tropisetron, a selective 5-HT3 (5-hydroxytriptamine) receptor antagonist, did not
      affect the emetic response evoked by ouabain. These results suggest that ouabain
      exerts emetic effects via peripheral mechanism(s), but 5-HT3 receptors are not
      involved in the pathway.

PMID- 9178927
TI  - Aromatase inactivation by a suicide substrate, androst-5-ene-4,7,17-trione: the
      5beta,6beta-epoxy-19-oxo derivative, as a possible reactive electrophile
      irreversibly binding to the active site.
AB  - In order to understand the mechanism involved in the aromatase inactivation by
      androst-5-ene-4,7,17-trione (4), a suicide substrate of aromatase, 5beta,6beta
      epoxyandrosta-4,7,17,19-tetraone (6) was synthesized as a candidate for a
      reactive electrophile involved in irreversible binding to the active site of
      aromatase upon treatment of 19-oxo-5-ene steroid 5 with hydrogen peroxide in the
      presence of NaHCO3. The epoxide 6 was a competitive inhibitor of human placental
      aromatase (Ki = 34 microM); moreover, it inactivated the enzyme in an active-site
      directed manner in the absence of NADPH (Ki = 36 microM, a rate constant for
      inactivation (k(inact)) = 0.027 min(-1)). NADPH stimulated the inactivation rate,
      but the substrate androst-4-ene-3,17-dione blocked the inactivation. A
      nucleophile, L-cysteine, did not cause a significant change in the inactivation.
      When both the epoxide 6 and its 19-methyl analog 7 were subjected separately to a
      reaction with N-acetyl-L-cysteine in the presence of NaHCO3, the 19-oxo compound
      6 disappeared from the reaction mixture more rapidly (t1/2 = 6.0 min) than the 19
      methyl analog 7 (t1/2 = 16 min). On the basis of these results, it is suggested
      that the 5beta,6beta-epoxy-19-oxo steroid 6 may be the reactive electrophile that
      alkylates a nucleophilic residue of the amino acid of the active site.

PMID- 9178928
TI  - Evaluation of propolis. I. Evaluation of Brazilian and Chinese propolis by
      enzymatic and physico-chemical methods.
AB  - To establish a method of evaluating propolis, the effects of the ethanol and
      water extracts from various collecting of propolis from different countries and
      plant sources on hyaluronidase activity were investigated along with their
      absorption spectra and specific absorbance (E(1%)1 cm value). The relations
      between the hyaluronidase inhibitory activities of these extracts and their
      E(1%)1 cm values were also examined, and the following was found: 1) the enzyme
      inhibitory activities of the ethanol extracts were more potent than those of the
      water extracts; 2) the enzyme inhibitory activities of the ethanol extracts from
      Araucaria angustifolia (BERT.) O. KTZE were low compared with those of other
      ethanol extracts; 3) the enzyme inhibitory activities of all the ethanol extracts
      correlated excellently with their E(1%)1 cm values, but in the water extracts,
      they decreased with increase in E(1%)1 cm values; 4) the water extracts of
      Chinese propolis from Hebei, Jiangsu, Sichuan and Zhejiang Provinces inhibited
      weakly compared with that from Brazilian and other Chinese propolis; 5) the
      shapes of absorption bands of the propolis extracts and the E(1%)1 cm values were
      approximately dependent on the place or the plant source from which propolis was
      collected. These experimental results indicated that, for the exact evaluation of
      propolis, the enzymatic method, measuring the hyaluronidase inhibitory activity,
      was superior to the physicochemical method.

PMID- 9178929
TI  - Random amplified polymorphic DNA analysis and variation of essential oil
      components of Atractylodes plants.
AB  - Total DNAs were prepared from the leaves of Atractylodes lancea DE CANDOLLE, A.
      chinensis KOIDZUMI, A. lancea var. simplicifolia KITAMURA, A. japonica KOIDZUMI
      ex KITAMURA and A. ovata DE CANDOLLE. The DNAs were subjected to random amplified
      polymorphic DNA (RAPD) analysis. Some primers showed the definitive polymorphic
      DNA patterns in A. lancea, A. japonica and A. ovata. The RAPD of A. lancea var.
      simplicifolia and one of A. chinensis gave similar patterns to those of A.
      lancea, but one of the other A. chinensis gave a similar pattern to A. japonica.
      Furthermore, quantitative analysis of atractylon, hinesol, beta-eudesmol and
      atractylodin in the rhizomes was done using gas chromatography. Though atractylon
      was detected not only in A. japonica and A. ovata but also in some of A. lancea,
      their RAPD profiles revealed the presence of intraspecific variation with A.
      lancea.

PMID- 9178930
TI  - Docosahexanoic acid (DHA) improved glucose and lipid metabolism in KK-Ay mice
      with genetic non-insulin-dependent diabetes mellitus (NIDDM).
AB  - The hypoglycemic and hypolipidemic effect of docosahexaenoic acid (DHA; C22:
      6omega-3) ethyl ester was examined in KK-Ay mice and neonatal streptozotocin
      induced diabetic (NSZ) which are respectively obese and lean animal models of non
      insulin-dependent diabetes mellitus (NIDDM), and in ddY normal mice. Single
      administration of DHA (500 mg/kg body weight) to KK-Ay mice significantly reduced
      (p<0.05) the blood glucose levels (BG) (p<0.05) and plasma free fatty acid levels
      (FFA) (p<0.05) at 10 h after oral administration when compared with control
      group. DHA (500 mg/kg body weight)-treated NSZ and normal mice, however, showed
      no change in these parameters. In addition, repeated administration of DHA (100
      mg/kg) to KK-Ay mice significantly suppressed the increment of BG (p<0.05) and
      plasma triglyceride levels (TG) (p<0.01), and significantly decreased FFA
      (p<0.05) at 30 d compared with control group. DHA also significantly decreased
      the blood glucose at 60 and 120 min on insulin tolerance test (ITT). From these
      findings, it seems likely that DHA exhibits its hypoglycemic effects by
      increasing insulin sensitivity. It is concluded that DHA would be useful for
      treatment of obese type NIDDM with insulin resistance.

PMID- 9178931
TI  - Studies on Alismatis rhizoma. I. Anti-allergic effects of methanol extract and
      six terpene components from Alismatis rhizoma (dried rhizome of Alisma
      orientale).
AB  - Methanol and aqueous extracts (TMe-ext and TAq-ext) from dried rhizomes of Alisma
      orientale have been screened for activity in experimental models of type I-IV
      allergies. In the type III allergic model, TMe-ext at oral doses of 50, 200 mg/kg
      showed an inhibitory effect on the direct passive Arthus reaction (DPAR) in rats,
      while TAq-ext did not. Four triterpenes (alisol A, alisol B, alisol A monoacetate
      and alisol B monoacetate) and two sesquiterpenes (alismol and alismoxide)
      isolated from TMe-ext also exhibited this inhibitory effect. In a type I allergic
      model, TMe-ext inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in
      rats. In a type II allergic model, it was found that TMe-ext inhibits reversed
      cutaneous anaphylaxis (RCA) in rats. Furthermore, in a type IV allergic model,
      TMe-ext had an inhibitory effect on the induction phase in picryl chloride
      induced contact dermatitis (PC-CD) in mice. These results indicate that Alismatis
      Rhizoma not only inhibits antibody-mediated allergic reactions but also
      influences cell reactions and should be recognized as a material for the
      treatment of allergic reactions, and the anti-type III allergic components are
      partially attributable to the terpenes mentioned above.

PMID- 9178932
TI  - Pharmacokinetic study of paeonimetabolin I, a major metabolite of paeoniflorin
      from paeony roots.
AB  - Plasma concentrations of paeoniflorin (PF) and its major metabolite,
      paeonimetabolin I (PM-I), were estimated after oral administration of PF to rats
      at doses of 0.5 and 5 mg/kg. The maximal plasma concentrations (Cmax) of PF were
      9.9 and 20.3, and those of PM-I were 16.5 and 101.7 ng/ml at each dose,
      respectively. The times to Cmax (tmax) of PF were 11.6 and 13.3, and those of PM
      I were 60 and 80 min, respectively. The AUC(0-180) of PM-I were 1873 and 12358,
      and those of PF were 300 and 1174 ng min/ml, respectively. On the other hand,
      after intravenous administration of PM-I to rats at doses of 0.2 and 2 mg/kg
      (equal in molar ratio to 0.5 and 5 mg/kg PF), the plasma concentration of PM-I
      decreased rapidly and the plasma concentration-time curve profile of it fitted
      well with the two-compartment model at each dose, with terminal half lives (t1/2)
      of 90.9 and 90.6 min. The Vdss values were 0.91 and 3.79 l/kg, the CLtot values
      were 8.7 and 39.9 ml/min kg, and the AUC(0-180) values were 5614.1 and 13176.0 ng
      min/ml, at each dose, respectively. The significant increase in Vdss and CLtot
      with increasing doses suggested dose-dependent pharmacokinetics. When PM-I was
      given orally at the same doses, the following parameters were shown: Cmax of
      102.2 and 285 ng/ml at tmax 6.2 and 7.5 min and AUCs of 4145.6 and 14182.1 ng
      min/ml, at each dose. The bioavailability (F) values were 0.8 and 1.07,
      respectively. These findings indicated that the high percentage of PM-I
      transformed by intestinal bacteria was rapidly absorbed from the gastrointestinal
      tract, and a significantly high concentration of PM-I, rather than PF, was
      present in the plasma after oral administration of PF.

PMID- 9178933
TI  - Biopharmaceutical studies on drug/conjugated-metabolite interactions. III. Effect
      of acetaminophen sulfate and its positional isomers on the pharmacokinetics of
      acetaminophen in rats.
AB  - The effect of three positional isomers, o-, m- and p-acetylaminophenyl sulfate
      (AOAPS, AMAPS and APAPS (acetaminophen sulfate), respectively), on the
      pharmacokinetics of acetaminophen (APAP) was investigated in rats. All of the
      intravenously administered positional isomers were rapidly eliminated from
      plasma, and approximately 80% of the dose was excreted in an unchanged form in
      the urine within 4 h, while biliary excretions represented a small percent of the
      doses. Following the intravenous bolus injection of APAP, plasma elimination of
      APAP was accelerated and the distribution volume of APAP was increased under a
      steady state concentration (about 10 microg APAP eq/ml) of AOAPS or APAPS, but
      not AMAPS, as compared with saline infusion. Total body clearances of APAP were
      increased from 18.3 ml/min/kg for the control to 23.9 and 26.9 ml/min/kg for
      AOAPS and APAPS coadministration, respectively. AOAPS and APAPS competitively
      displaced the serum protein binding of APAP, while AMAPS had little effect. The
      distribution volume of unbound APAP was anomalously increased by APAPS, while it
      was not affected by AOAPS or AMAPS. Tissue-to-plasma concentration ratios of APAP
      were significantly increased by APAPS in the liver, kidney and brain, while they
      were only slightly increased by AOAPS. It was suggested that APAPS has not only
      the displacing activity of serum protein binding but also other specific
      effectiveness on the distribution of APAP.

PMID- 9178934
TI  - Protective effect of transfection with secretable superoxide dismutase (SOD) (a
      signal sequence-SOD fusion protein coding cDNA) expression vector on superoxide
      anion-induced cytotoxicity in vitro.
AB  - For ex vivo gene therapy, superoxide dismutase (SOD) must be secreted into the
      extracellular space and delivered to damaged cells. Recombinant DNA technique can
      be used to produce a secretory protein that is fused to a non-secretory protein
      and a signal peptide of another secretory protein gene. We constructed a
      secretable SOD eukaryotic expression vector which expresses human SOD cDNA by
      fusing it to the signal peptide DNA sequence of the human interleukin-2 (IL-2)
      gene. The ILSOD cDNA constructed by PCR-based gene expression was ligated into
      the multicloning site of the pRc/CMV plasmid (pRc/CMV-ILSOD). Rat lung epithelial
      like cells (L2 cells) were transfected with pRc/CMV-ILSOD by lipofection. The
      extracellular SOD activity of ILSOD-L2 cells (transfected cells with pRc/CMV
      ILSOD) was 3 times as high as that of host cells. We used the xanthin (X)/xanthin
      oxidase (XO) system to produce superoxide anions at the extracellular space. We
      initially investigated the direct cytotoxicity of superoxide anions upon cells.
      Host and ILSOD-L2 cells were killed by using X/XO, although the sensitivity of
      the ILSOD-L2 cells to X/XO induced cytotoxicity was significantly decreased
      compared with that of host cells. The production of lipid peroxidated substances
      in the host in the presence of X/XO increased to about twice the control (absence
      of X/XO) level. However, that of ILSOD-L2 cells did not change in the presence of
      X/XO. Therefore, ILSOD-L2 cells were resistant to X/XO induced lipid
      peroxidation. These findings indicated that ILSOD gene transfection protected
      against direct oxidant stress by X/XO. We then investigated the effect of
      extracellular SOD secreted from ILSOD-L2 cells on extracellular superoxide anion
      induced cytotoxicity in normal cells. The conditioned media of host cells had no
      significant effect upon X/XO induced cytotoxicity. However, the conditioned media
      of ILSOD-L2 cells protected against X/XO induced cytotoxicity. Furthermore, the
      conditioned medium of ILSOD-L2 cells was more effective than that of host cells
      against the production of lipid peroxidated substances by normal cells under
      conditions of oxidative stress. These results indicated that non-secretable
      protein could be delivered to target cells by means of DNA engineering. This
      strategy could thus provide an ex vivo means of applying gene therapy using non
      secretable proteins.

PMID- 9178935
TI  - Prolongation of antidiuretic response to desmopressin acetate by iontophoretic
      transdermal delivery in rats.
AB  - An iontophoretic drug delivery system was compared with intranasal, oral and
      subcutaneous delivery from a standpoint of the prolongation of the antidiuretic
      response to desmopressin acetate (DDAVP) in diabetes insipidus rats.
      Iontophoretic delivery was comparable to the nasal route at a dose about five
      times higher than the nasal route dose, and was 2 to 3 times as effective as the
      oral route. Effect of dose and duration of current application on the
      prolongation of the response to DDAVP was also investigated in order to find the
      effectiveness of the iontophoresis. The antidiuretic response to DDAVP delivered
      by iontophoresis indicated a dose-dependent prolongation and was prolonged up to
      about 14 h with the increase of the duration of current application; when a
      pulsed direct current at 0.1 mA was passed for about 1 h, the response to DDAVP
      was prolonged for about 9 h. DDAVP in the anodic donor steeply decreased with the
      application for 1 h, and then gradually decreased. We suggest that the
      antidiuretic response to DDAVP can be effectively controlled by regulating the
      absorption of DDAVP at the short-term iontophoresis rather than prolonged
      treatment.

PMID- 9178936
TI  - Selective antitumor activity in vitro from marine algae from Japan coasts.
AB  - In vitro selective antitumor activity was tested as a general screening parameter
      for biologically active substances from a wide range of species of seaweed, 1446
      samples of 306 species of marine algae from Japan's coasts. The algae extracts
      were prepared successively first by phosphate buffered saline (PBS) and then by
      methanol, and then tested for in vitro selective antitumor activity against
      murine lymphoid leukemia L1210 cells and for low cytotoxic activity against NIH
      3T3 normal cells. Strong cytotoxic activity against L1210 cells was found in 47
      species of algae, also showing similar cytotoxicity to mouse NIH-3T3 normal
      cells. However, four species of green algae showed strong activity specifically
      against L1210 cells, with low cytotoxicity to normal cells. Such selective
      activity was conspicuous in two brown and two green algae extracts. In
      particular, methanol extracts from the green alga, Cladophoropsis
      vaucheriaeformis, exhibited high viability (86%) to normal cells, showing
      selective cytotoxicity to tumor cells. This alga extract was no cytocidalic, but
      cytostatic against L1210 cells. Furthermore, the results of a cytotoxic spectrum
      test with 9 cell lines including those of L1210 and NIH-3T3 demonstrated that
      this extract acted strongly only against leukemic cell lines L1210 and P388.

PMID- 9178937
TI  - Antiviral substance from silkworm faeces: purification and its chemical
      characterization.
AB  - In a previous paper, we reported that an extract of silkworm faeces has a marked
      antiviral activity on enveloped viruses, but not on a non-enveloped virus, and we
      showed that it inhibits the synthesis of a viral specific gene of HVJ (Sendai
      virus) without affecting the viral adsorption and entry into the host cell. In
      this paper, we accomplished the purification of an antiviral active substance by
      extraction of a hydrophobic substance and thin layer chromatography. The active
      substance was found to be a chlorophyll-like substance with a molecular mass of
      about 530. This substance shows clear antiviral activity against HVJ, HSV (herpes
      simplex virus type-1), and HIV (human immunodeficiency virus type-1). Its
      antiviral activity was dependent on light irradiation and temperature.
      Furthermore, it also possesses a strong hemolytic activity under light.

PMID- 9178938
TI  - Biochemical and immunochemical properties of modified human neuron-specific
      enolase.
AB  - 125I-Labeled recombinant human neuron-specific enolase (R-NSE) was inadequate for
      RIA as a labeled antigen. The binding activity of labeled R-NSE to the antibody
      was markedly decreased. To supplement this defect and facilitate purification, we
      constructed two R-NSE derivatives, Y-NSE (one tyrosine residue was added at the N
      terminal of R-NSE) and Y-NSE.H6 (six histidine residues were further added at the
      C-terminal of Y-NSE). The biochemical and immunochemical characteristics of these
      R-NSE derivatives were essentially the same to those of R-NSE. These derivatives
      were useful not only as standards for enzyme immunoassay (EIA), but also as
      labeled antigens for RIA. These results clearly indicate that the reactivity of
      these modified NSEs to anti-NSE antibody is almost equivalent to that of human
      brain gammagamma-enolase (B-NSE), and that even if the modified NSEs are labeled,
      they retain their binding affinities to antibodies in contrast to R-NSE.

PMID- 9178939
TI  - Grapefruit component interacting with rat and human P450 CYP3A: possible
      involvement of non-flavonoid components in drug interaction.
AB  - Active components in grapefruit juice, which modulate a cytochrome P450 (CYP3A)
      activity, were investigated. CYP3A-catalyzed 6beta-hydroxylation of testosterone
      in livers of rat and human was inhibited by the addition of an ethyl acetate
      extract of grapefruit juice. Several components of grapefruit juice, including
      naringin, naringenin, limonin and obacunone, also showed inhibitory effects in
      human liver microsomes. However, the amounts of these components in grapefruit
      juice are too low to account for the inhibition by the ethyl acetate-extracts.
      Analyses with HPLC indicate the existence of inhibitory components in the
      extract, which are distinct from these known compounds and are specific to
      grapefruit juice. These results suggest that hydrophobic components other than
      flavonoids, probably coumarin derivatives, are responsible for the inhibitory
      effect of grapefruit juice.

PMID- 9178940
TI  - Anti-allergic effect of tea-leaf saponin (TLS) from tea leaves (Camellia sinensis
      var. sinensis).
AB  - We investigated the anti-allergic effect of tea-leaf saponin (TLS), which was a
      mixture of saponins separated from the leaves of Camellia sinensis var. sinensis,
      in guinea pigs and rats. TLS (20-100 mg/kg) dose-dependently inhibited
      experimentally-induced asthma, and ID50 was 61.7 mg/kg. TLS (20-100 mg/kg) dose
      dependently inhibited a 48 h homologous PCA (passive cutaneous anaphylaxis)
      reaction, and the inhibitory effect was similar to that of tranilast. TLS (1-100
      microg/ml) also inhibited the release of antigen-induced leukotriene (LT) C4 from
      sensitized guinea pig lung samples in a dose-dependent fashion, but did not
      prevent histamine release. TLS (0.01-0.5 microg/ml) inhibited histamine release
      from rat peritoneal mast cells induced by compound 48/80. At higher
      concentrations, TLS elicited histamine release. These findings suggest that TLS
      may be a useful protective agent against clinical allergy, and that the
      inhibitory effects of TLS on mediator release are in some way related to its
      inhibitory effect on experimentally-induced asthma and PCA reaction.

PMID- 9178941
TI  - Flow regulates vasodilator responses to acetylcholine in the isolated canine
      mesenteric arterial bed.
AB  - Raising the flow rate of the perfusate from 10 to 20 ml/min significantly
      suppressed vasodilator responses to acetylcholine, but not to sodium
      nitroprusside, in the isolated canine mesenteric arterial bed. Both acetylcholine
      and sodium nitroprusside augmented guanosine 3',5'-cyclic monophosphate (cyclic
      GMP) levels in the effluent from the vascular bed preparation, though cyclic GMP
      responses to these agents were not affected by raising the flow rate. These data
      suggest that the suppression, via raising the flow rate, of vasodilator responses
      to acetylcholine is not due to impaired function of the nitric oxide (NO)-cyclic
      GMP pathway in the mesenteric arterial bed.

PMID- 9178942
TI  - Electronic and structural requirements for metabolic activation of butylated
      hydroxytoluene analogs to their quinone methides, intermediates responsible for
      lung toxicity in mice.
AB  - Previous studies have shown that butylated hydroxytoluene (BHT) undergoes
      oxidation by cytochrome P450 to form BHT-quinone methide. BHT-quinone methide is
      probably responsible for BHT-induced lung damage in mice. In this study, we
      calculated the MO parameters for BHT analogs and the corresponding quinone
      methide intermediates. Except for the analogs with structures that form a highly
      sterically hindered quinone methide, correlations could be established between
      the lung toxicity in mice and electronic charges on the hydroxyl oxygen and 4
      carbon atoms of BHT analogs. The same toxicity could also be correlated to the
      difference between the heat of formation of the quinone methide intermediates and
      the parent BHT analogs, and to the electronic charge on the carbonyl oxygen atom
      of the quinone methides. These results suggest that the metabolic activation of
      BHT analogs to their quinone methide intermediates is energetically dependent on
      the oxidation of the aromatic pi-electron system, and that the toxic potency of
      BHT analogs is controlled by protonation of the oxygen atom of the quinone
      methides. These electronic features provide further evidence of the importance of
      the quinone methide intermediates in the mechanism of lung toxicity induced by
      BHT analogs.

PMID- 9178943
TI  - Effect of polyethyleneglycol 4000 (PEG4000) solution on the in vitro release
      profile of nifedipine from polymer matrices.
AB  - The effect of PEG4000 solution on the in vitro release of nifedipine, a calcium
      entry blocker and a poorly water soluble drug was evaluated. Nifedipine tablets
      containing 10 mg of nifedipine, 20% of one four polymers--Eudragit L-100 and Rs,
      ethylcellulose and carbopol 941, 2% lubritab and an adequate quantity of
      Encompress to yield 300 mg weight tablets--were formulated using the direct
      compression method. Tablets were compressed to a hardness of 5N, and an in vitro
      dissolution profile was performed on the tablets in 70% ethanol and in ethanolic
      PEG4000 solutions. The results obtained indicated enhancement of nifedipine
      release from two of the polymer matrices (Eudragit L-100 and ethylcellulose) in
      the presence of PEG4000 and a retardant effect from carbopol 941 matrix. It is
      suggested that carbopols may not be suitable for use in the formulation of
      nifedipine tablets since there are some physiological surfactants present in the
      gastrointestinal tract (GIT).

PMID- 9178944
TI  - Kinetics of nikkomycin Z degradation in aqueous solution and in plasma.
AB  - The stability of nikkomycin Z in aqueous solution at various pH values and in the
      plasma of several kinds of experimental animals was studied. The degradation of
      nikkomycin Z in aqueous solution at pH 4 to 11.5 and in plasma was an apparent
      first-order reaction. The degradation rate at 37 degrees C increased with
      increasing pH, from 4.0 to 7.5, and decreased with increasing pH from 7.5 to
      10.2. Above pH 10.2, the degradation rate was constant. The maximal rate of
      nikkomycin Z degradation was observed in pH 7.5 buffer solution, in which the
      apparent first-order rate constant (k(obs)) was 8.08 x 10(-2) h(-1) (t1/2 = 8.6
      h). The degradation rate of nikkomycin Z in dog plasma at 37 degrees C was the
      almost same as that in pH 7.5 buffer. The rates in rat, mouse, and rabbit plasma
      were much greater than that in pH 7.5 buffer; the k(obs) values for rat, mouse,
      rabbit, and dog plasma at 37 degrees C were 1.74 x 10(-1) min(-1), 3.64 x 10(-2)
      min(-1), 5.10 x 10(-1) h(-1), and 6.14 x 10(-2) h(-1), respectively. The
      degradation rate of nikkomycin Z in rat plasma was markedly decreased when NaF,
      an esterase inhibitor, was added to the plasma. The findings of faster
      degradation rates in rat, mouse, and rabbit plasma compared with that in pH 7.5
      buffer were considered to be due to an esterase in the plasma. This notion was
      supported by results showing the degradation rate of nikkomycin Z in porcine
      liver esterase solution.

PMID- 9178945
TI  - Development of a membrane fusible drug carrier from erythrocytes by the
      spontaneous transfer of viral fusion protein from influenza virus-infected cells.
AB  - In order to develop a membrane fusible drug carrier from human erythrocytes, we
      attempted the reconstitution of influenza virus fusion protein hemagglutinin (HA)
      to an erythrocyte membrane. In this study, we succeeded in the preparation of HA
      reconstituted erythrocytes (HA-erythrocytes) by the incubation of erythrocytes
      with influenza virus-infected CV-1 cells, and confirmed the ability of HA
      erythrocytes to fuse with the cell membrane. Furthermore, by using an HA
      reconstituted ghost (HA-ghost), which entrapped fluorescent-labeled ovalbumin,
      25% of the protein was incorporated into cells through the fusion of the HA-ghost
      with the cell membrane.

PMID- 9178946
TI  - In vitro susceptibility of Escherichia coli O157 to several antimicrobial agents.
AB  - We evaluated the antimicrobial susceptibility of six strains of Escherichia coli
      O157 (E. coli O157) isolated from patients in Yamaguchi Prefecture between June
      and July, 1996. Seven antimicrobial agents that were expected to retain a high
      concentration in the intestine were selected. The minimum inhibitory
      concentration (MIC) and the minimum bactericidal concentration (MBC) of
      ciprofloxacin, polymyxin B, cefoperazone, and kanamycin for each strain were < or
      = 6.25 microg/ml. However, the MIC of fosfomycin was 3.13-100 microg/ml, and its
      MBC was > or = 100 microg/ml. The MIC of ampicillin and tetracycline was > 100
      mcirog/ml in some strains. In a time-kill study of E. coli O157 at a drug
      concentration of 12.5 microg/ml, about 10(4) colony forming units/ml of E. coli
      O157 were eradicated within 10 min by ciprofloxacin, within 30 min by polymyxin
      B, within 4 h by cefoperazone, and within 16 h by kanamycin. These results
      suggest that the new quinolones with a poor absorption rate in the intestine
      (such as ciprofloxacin and norfloxacin) are effective against E. coli O157. When
      oral administration is impossible, bile excreting cephem antibiotics (such as
      cefoperazone, ceftriaxone, and cefotetan) may be useful.

PMID- 9178947
TI  - Norreticuline and reticuline as possible new agents for hair growth acceleration.
AB  - (S)-Norreticuline and (S)-reticuline have been shown to stimulate the
      proliferation of cultured cells from the murine hair apparatus significantly.
      Furthermore, these activities were found on cultured hair cells, but not on
      cultured keratinocytes or fibroblasts from murine skin. In addition, (S)
      norreticuline significantly stimulated mouse hair regrowth. These results suggest
      that (S)-norreticuline and (S)-reticuline could have specific activities on hair
      apparatus cells and might be useful as active compounds for accelerating hair
      growth.

PMID- 9178948
TI  - Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated
      signal transduction at the synapse.
AB  - [4,5-3H]Docosahexaenoic acid ([3H]DHA) or [9,10-3H]palmitic acid ([3H]PAM) was
      infused intravenously for 5 min to awake, adult male rats before and after
      treatment with arecoline (15 mg/kg, i.p.), a cholinergic agonist. Animals were
      killed 15 min post-infusion, the brains were rapidly removed and subcellular
      fractions were obtained after sucrose density centrifugation. In control animals,
      [3H]DHA and [3H]PAM were incorporated into the synaptosomal fractions,
      representing 50%-60% of total membrane label. Most remaining membrane label (30%
      40%) was in the microsomal fraction. Both fractions contained the synaptic marker
      synaptophysin. The remaining 10% of radioactivity was in the myelin and
      mitochondrial fractions. Arecoline significantly increased [3H]DHA entry into the
      synaptosomal fractions by 100% and into the microsomal fraction by 50%. In these
      fractions 60%-65% of the [3H]DHA was in phospholipid, the rest corresponding to
      free fatty acid and diacylglycerol. In contrast, arecoline did not change [3H]PAM
      incorporation into any brain fraction. These results demonstrate that plasma
      [3H]DHA incorporation is selectively increased into synaptic membrane
      phospholipids of the rat brain in response to cholinergic activation. The
      increased incorporation of DHA but not of PAM into synaptic membranes in response
      to cholinergic stimulation indicates a primary role for DHA in phospholipid
      mediated signal transduction at the synapse involving activation of phospholipase
      A2 and/or C.

PMID- 9178949
TI  - Membrane fatty acid modifications of PC12 cells by arachidonate or
      docosahexaenoate affect neurite outgrowth but not norepinephrine release.
AB  - The relationships between membrane fatty acid modification and neurite outgrowth
      and norepinephrine release were evaluated in PC12 cells. [3H]Norepinephrine
      release evoked by carbachol was unaffected by the modifications. Basal
      spontaneous release was elevated with increases in the degree of unsaturation
      using cells supplemented with n-3 fatty acids; a reverse correlation was observed
      for [3H]norepinephrine uptake. Supplementation of PC12 cells with either n-6
      fatty acids or 18:1 also increased the basal release and decreased the uptake.
      Docosahexaenoic acid promoted and arachidonic acid suppressed neurite outgrowth
      induced by nerve growth factor. Choline acetyltransferase activity was slightly
      influenced by these fatty acids. Thus, modifications of PC12 cells with
      arachidonic acid and docosahexaenoic acid had a relatively small effect on the
      degree of differentiation but had pronounced but opposite effects on neurite
      elongation. Ethanolamine glycerophospholipid synthesis was elevated during
      differentiation induced by nerve growth factor and it was suppressed by added
      arachidonic acid but not by docosahexaenoic acid. Our results raise the
      possibility that the decreased phospholipid synthesis caused by arachidonate may
      lead to the suppression of neurite elongation.

PMID- 9178950
TI  - Activation of p42 mitogen-activated protein kinase by glutamate in cultured
      radial glia.
AB  - The effect of L-glutamate (Glu) and its structural analogs N-methyl-D-aspartate
      (NMDA), kainate (KA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA), on the activation of p42 mitogen activated protein kinase (MAPK) was
      examined in cultured chick radial glia cells, namely retinal Muller cells and
      cerebellar Bergmann cells. Glu, NMDA, AMPA and KA evoked a dose and time
      dependent increase in MAPK activity. AMPA and KA responses were blocked by 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX) whereas NMDA responses were sensitive
      to 3-[(RS)-2-carboxypiperazin-4-yl)]-propyl-1-phosphonate (CPP) indicating that
      the increase in MAPK activity is mediated by AMPA/low affinity KA and NMDA
      subtypes of Glu receptors. The present findings open the possibility of a MAPK
      cascade involvement in the regulation of Glu-induced gene expression in radial
      glia.

PMID- 9178951
TI  - Regional distribution of phospholipids and polyphosphatidyl inositides in the
      rabbit's spinal cord.
AB  - The plasticity of the membrane phospholipids in general and stimulated
      phosphoinositides turnover in particular are the subjects in a variety of neural
      paradigms studying the molecular mechanisms of neuronal changes under normal and
      pathological conditions. The regional modifiability of phospholipids (SM, PC, PS,
      PI, PA + DG, PE), polyphosphatidylinositides (PI, PIP, PIP2) and diacylglycerol
      dependent incorporation of CDP-choline into phosphatidylcholine in the gray
      matter, white matter, dorsal horns, intermediate zone and ventral horns of the
      rabbit's spinal cord was studied. We have found 1. a significant increase in the
      concentration of SM, PC, PS, DG + PA and PE in the white matter in comparison to
      the gray one, 2. the highest concentration of the outer membrane leaflet-bound
      phospholipids in the dorsal horns and the inner membrane phospholipids in the
      intermediate zone in comparison to the gray matter, 3. a substantial amount of
      labeled polyphosphatidylinositides (poly-PI(s)) in the spinal cord white matter
      with descending order PIP > PI > PIP2, 4. similar incorporation of myo-2
      [3H]inositol into all poly-PI(s) in ventral horns and intermediate zone, but a
      different, lower incorporation into PI and PIP and higher into PIP2 in the dorsal
      horns, 5. higher diacylglycerol-dependent incorporation of CDP-choline into PC in
      the regionally undivided gray matter than in the white matter taken as a whole,
      6. the high proportion of diacylglycerol-dependent incorporation of CDP-choline
      into PC in both the ventral and dorsal horns, whereas that in the intermediate
      zone remained low.

PMID- 9178952
TI  - Antagonism of convulsions but failure to enhance GABA(A) receptor function by
      felbamate in mice tolerant to diazepam.
AB  - The transfer of tolerance between drugs may indicate a common mode of action. The
      development of cross-tolerance to the anticonvulsant effect of felbamate after
      long-term treatment of mice with diazepam, a positive modulator of gamma
      aminobutyric acid (GABA)-mediated transmission, was therefore studied in order to
      clarify the mechanism of this action of felbamate. A challenge injection of
      felbamate, administered 36 h after the last dose of chronic diazepam treatment,
      antagonized convulsions elicited by administration of isoniazid. In contrast,
      felbamate had no effect on the isoniazid-induced increase in t
      [35S]butylbicyclophosphorothionate binding to cerebral cortical membranes of
      diazepam-tolerant mice. These results suggest that the action of felbamate on
      GABAergic transmission is not required for the anticonvulsant effect of this
      drug. This conclusion is consistent with studies that have indicated that the
      antiepileptic activity of felbamate depends on its modulatory activity at
      excitatory amino acid receptors.

PMID- 9178953
TI  - Effect of ethanol on nuclear casein kinase II activity in brain.
AB  - Casein kinase II (CK II) plays an important role in serine/threonine dependent
      protein phosphorylation. In brain it is associated with long term potentiation
      besides its involvement in DNA, RNA and protein metabolism. Ethanol has been
      shown to induce cognitive impairment and affects DNA, RNA and protein metabolism
      at various steps. Since CK II is central in all these events, which are
      specifically affected by ethanol, the role of nuclear CK II is investigated in
      the present study. Total nuclear casein kinase activity was unaffected while
      heparin sensitive nuclear casein kinase II activity showed a 30% decrease in the
      brain from chronic alcohol fed rats. Cytosolic CK II activity was also
      unaffected. Immunological detection by western analysis using CK II antibodies
      showed no alteration in the quantity of enzyme. The decrease in nuclear casein
      kinase II might be responsible for ethanol induced cognitive impairment in the
      brain.

PMID- 9178954
TI  - Effects of excitatory amino acids on cerebral oxygen consumption and blood flow
      in rat.
AB  - This investigation tested the importance of excitatory amino acids' effects on
      regional cerebral O2 consumption and the concomitant changes in cerebral blood
      flow (rCBF) in isoflurane anesthetized rats. In the glutamate or N-methyl-D
      aspartate (NMDA) groups, 10(-2) M glutamate or NMDA was topically applied to the
      right cortex and the left cortex was used as a control. One mg/kg dizocilpine
      maleate (MK-801), a non-competitive NMDA receptor antagonist, was administered
      (iv) to the MK-801 group and saline was given to the control group. Cortical rCBF
      was determined using 14C-iodoantipyrine and regional O2 extraction was measured
      microspectrophotometrically. Cerebral O2 consumption increased 77% after
      glutamate (contralateral cortex: 9.0 +/- 1.1 ml O2/min/100 g, glutamate treated
      cortex: 15.9 +/- 3.9), while a 46% increase was observed with the same
      concentration of NMDA (contralateral cortex: 9.8 +/- 2.0, NMDA treated cortex:
      14.3 +/- 5.5). After MK-801, the O2 consumption decreased to 37% of the control
      value (control cortex: 7.0 +/- 1.3, MK-801 treated cortex: 2.6 +/- 3.9). MK-801
      significantly decreased cerebral O2 extraction from 7.1 +/- 1.3 ml O2/100 ml
      (control cortex) to 5.3 +/- 0.6 (MK-801 treated cortex). However, there was no
      significant difference in cerebral O2 extraction between treated and
      contralateral cortex in either the glutamate or NMDA groups. The increase in O2
      consumption caused by glutamate or NMDA was coupled with increased rCBF.
      Glutamate increased rCBF from 95 +/- 5 ml/min/100 g (contralateral cortex) to 165
      +/- 31 (treated cortex), while NMDA increased rCBF from 114 +/- 12 (contralateral
      cortex) to 178 +/- 60 (treated cortex). MK-801 decreased O2 consumption with a
      lesser decrease of rCBF. The rCBF was 48 +/- 9 in the MK-801 treated cortex and
      99 +/- 22 in the control cortex. Some substances produced by the activation of
      NMDA receptors may be related to the coupling of cerebral metabolism and blood
      flow, since after blockade of NMDA receptors with MK-801, this relationship is
      uncoupled. These findings suggest that glutamatergic processes have a major
      effect on cerebral O2 consumption and that this is at least partly due to NMDA
      receptors.

PMID- 9178955
TI  - Age-dependent organotypic expression of microtubule-associated proteins (MAP1,
      MAP2, and MAP5) in rat brain.
AB  - Age-dependent changes in the distribution of microtubule-associated proteins
      (MAPs) were analyzed in young (3-months, N = 3) and old (24-months, N = 3) rat
      brain. In the young rats, MAP1 and MAP5 exhibited prominent immunostaining in the
      perikarya and dendrites whereas MAP2 was selectively localized in the dendrites.
      In the cerebellum, MAP2 was preferentially localized in finer and distal branches
      of Purkinje cell dendrites and in punctate deposits surrounding glomeruli. In
      general, aging resulted in obvious declines in MAP2- >> MAP1- and MAP5
      immunoreactivities in the hippocampus and parietal cortex but no change in
      cerebellum. The results indicate that: (1) hippocampus is the most affected and
      cerebellum is the least affected region with regard to declines in MAPs
      immunoreactivities in the aged rat brain; (2) dendrite-specific MAP2 is almost
      completely depleted from most dendrites in the hippocampus and cortex. In
      summary, loss of MAP2-immunoreactivity in the affected brain areas may be
      associated with age-related impairment of synaptic plasticity, cognition and
      memory functions.

PMID- 9178956
TI  - The rapid L- and D-aspartate uptake in cultured astrocytes.
AB  - Astrocytes in primary culture possess a rapid L-aspartate saturable transport
      system (K(m) = 93 microM; V(max) = 81 nmol/min/mg protein), which shows certain
      stereospecificity since V(max) was 36% lower for D-aspartate uptake. These are
      values obtained at short incubation time (15 seconds), to obtain approximate
      initial rate conditions. Metabolic energy inhibitors, rotenone and iodoacetate
      very potently inhibited the L- and D-aspartate uptake processes, indicating that
      the transport process is an active one. However, the accumulation of L-aspartate
      was "enhanced" by inhibitors of L-aspartate metabolism, such as the aspartate
      aminotransferase inhibitor, aminooxyacetate and L-methionine sulfoximine, an
      inhibitor of glutamine synthetase, whereas D-aspartate (a non-metabolizable
      analog of L-aspartate) uptake was not affected. The accumulated levels of L
      aspartate in the presence of aminooxyacetate were similar to the levels of D
      aspartate. These effects of L-aspartate metabolic inhibitors, suggest that due to
      metabolism of the the L-aspartate, short incubation time (eg., 15 seconds) is
      necessary to measure the initial rate of L-aspartate uptake, in order to obtain
      the "true" kinetic parameters.

PMID- 9178957
TI  - The gamma-glutamyl transpeptidase inhibitor acivicin preserves glutathione
      released by astroglial cells in culture.
AB  - The release of glutathione from astroglial cells was investigated using astroglia
      rich primary cultures prepared from the brains of newborn rats. These cells
      release glutathione after onset of an incubation in a glucose-containing minimal
      medium. The amount of extracellular glutathione increased with the time of
      incubation, although the accumulation slowed down gradually. An elevated rate of
      increase of the glutathione concentration in the incubation medium was found if
      the astroglial ectoenzyme gamma-glutamyl transpeptidase was inhibited by
      acivicin. The activity of gamma-glutamyl transpeptidase in astroglia-rich primary
      cultures, which was found to be 1.9 +/- 0.3 nmol/(min x mg protein), was markedly
      reduced if the cells had been incubated in the presence of acivicin. After 2 h of
      incubation with acivicin half-maximal and maximal inhibition of gamma-glutamyl
      transpeptidase activity was found at concentrations of about 5 microM and 50
      microM, respectively. In the presence of acivicin at a concentration above 10
      microM the glutathione content found released from astroglial cells apparently
      increased almost proportional to time for up to 10 h. Under these conditions the
      average rate of release was 2.1 +/- 0.3 nmol/(h x mg protein) yielding after a 10
      h incubation an extracellular glutathione content three times that of the medium
      of cells incubated without inhibitor. Half-maximal and maximal effects on the
      level of extracellular glutathione were found at 4 microM and 50 microM acivicin,
      respectively. After a 10 h incubation with acivicin the intracellular content of
      glutathione was reduced to 75% of the level of untreated astroglial cultures.
      These results suggest that glutathione released from astroglial cells can serve
      as substrate for the ectoenzyme gamma-glutamyl transpeptidase of these cells.

PMID- 9178958
TI  - Redox changes in perfusates following intracerebral penetration of microdialysis
      probes.
AB  - Microdialysis probe insertion into rat cerebral cortex significantly affects the
      levels of redox-active substances in brain extracellular fluid. Ascorbic acid
      levels are high immediately after probe insertion, decline rapidly, and then rise
      as the rat recovers from anesthesia 5-8 hours after surgery. Uric acid is at a
      low level for 5 hours and then rapidly increases in parallel with ascorbic acid.
      High ascorbic acid levels immediately after probe insertion are likely due to a
      shift from intracellular to extracellular fluids, whereas the delayed increase in
      uric acid may be due to increased enzymatic formation. After removal from the
      brain, hydrogen peroxide (H2O2) in microdialysis samples produces catalase
      sensitive oxidative chemiluminescence. Microdialysis samples also produce high
      level catalase-resistant chemiluminescence associated with ascorbic acid levels
      after penetration injury. Although ascorbic acid is likely an antioxidant at
      concentrations estimated to be in brain extracellular fluid, it may have
      prooxidant effects when complexed with transition metals released into the
      neuronal microenvironment during traumatic brain injury.

PMID- 9178960
TI  - [3H]ketanserin binding in human brain postmortem.
AB  - This study aimed at comparing the binding characteristics of [3H]ketanserin, a
      high-affinity serotonin 2A (5-HT2A) receptor antagonist, in the prefrontal
      cortex, hippocampus and striatum of human brain post-mortem. The results
      indicated the presence of a single population of binding sites in all the regions
      investigated, with no statistical difference in maximum binding capacity (B(max))
      or dissociation constant (K(d)) values. The pharmacological profile of
      [3H]ketanserin binding was consistent with the labeling of the 5-HT2A receptor,
      since it revealed a competing drug potency ranking of ketanserin = spiperone >
      clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5
      HT2A receptor, as labeled by [3H]ketanserin, would seem to consist of a
      homogenous population of binding sites and to be equally distributed in human
      prefronto-cortical, limbic and extrapyramidal structures.

PMID- 9178959
TI  - Postresuscitation changes in brain free radical-mediated processes and nitric
      oxide synthase activity in rats: effects of individual behavior in "emotional
      resonance" test.
AB  - Effects of 7-min cardiac arrest and individual behavior on free radical-mediated
      processes and nitric oxide synthase (NOS) activity was evaluated in brains of
      male Wistar rats one hour and one week after resuscitation. "Emotional resonance"
      test was used for the behavioral selection of rats. The test includes factors of
      significance for rats: the choice between large and lighted or small and dark
      space as well as signals of pain of another rat. Free radical generation (using
      chemiluminescence method), superoxide scavenging/generating activity, substances
      reacting with 2-thiobarbituric acid and NOS activity (by measuring mononitrosyl
      iron complex of NO with diethyl dithiocarbamate and endogenous brain Fe2+ by
      electron spin resonance spectroscopy) were determined in cerebral cortex,
      cerebellum and hippocampus. Cardiac arrest induced oxidative stress accompanied
      by the loss of NOS activity, as well as compensatory changes of free radical
      mediated processes in cerebral cortex. Oxidative stress was also evident in
      cerebellum and, to a lesser extent, in hippocampus. Most of neurochemical
      differences between behavioral groups were induced by cardiac arrest. These
      differences were global, related to a specific brain region or became apparent in
      cerebral lateralization of biochemical indices.

PMID- 9178961
TI  - Props and children's event reports: the impact of a 1-year delay.
AB  - Three- and 5-year-old children took part in a quasi-medical event in which the
      child and an adult stranger examined a "sick" teddy bear. Three days and 1 year
      after the event, children were interviewed in one of three interview conditions;
      with real items from the event (real props); with toy representations of those
      items (toy props); or with verbal prompts (no props). After 3 days, both toys and
      real items facilitated children's reports compared to verbal prompts, but
      children interviewed with toy props were less accurate than those interviewed
      with either real items or verbal prompts. After 1 year, the reports of children
      interviewed with real items remained more accurate than those of children
      interviewed with toys, although real items did not differentially protect recall
      from forgetting compared to either toys or verbal prompts. The report of the
      older children were as accurate at the 1-year delay as at the 3-day delay,
      whereas the reports of the younger children were particularly susceptible to
      errors. Correct information was more likely to be repeated across interviews than
      were errors. New information introduced for the first time after 1 year was
      highly unreliable for both age groups, whereas that repeated across interviews
      was highly reliable.

PMID- 9178962
TI  - Means to the goal of remembering: developmental changes in awareness of strategy
      use--performance relations.
AB  - We examined awareness of the causal relation between strategy use and recall
      performance among preschoolers, first graders, and third graders, and the
      relation of this awareness to children's study behavior and recall. In session 1,
      children were presented with two study-recall trials; the second trial included
      questions concerning the child's study behavior. During Session 2, children
      viewed videotapes in which a model's strategy use (labeling versus no labeling)
      and recall level (high versus low) were varied orthogonally. Children judged
      whether the model tried to remember, rated how hard the model tried to remember,
      and described how they knew. Children who gave mentalistic explanations for their
      study behaviors in Session 1 recalled more than those giving nonmentalistic
      explanations. In Session 2, age-related differences were observed in awareness of
      the relation between strategy use and performance level. Further, children who
      demonstrated understanding of strategy use-performance relations in Session 2
      were more likely to give mentalistic explanations for their own study behaviors
      in Session 1. The results further delineate the metamemorial development that
      contributes to effective strategy utilization.

PMID- 9178963
TI  - Sources of interference from irrelevant information: a developmental study.
AB  - The present study investigated the mechanisms underlying reductions in the
      susceptibility to interference from irrelevant information that are evident in
      the developing child. In the first experiment, where the task was to focus on one
      stimulus dimension and to ignore a second dimension, variations in the degree of
      spatial integration in multidimensional stimulus configurations did not influence
      interference effects. Developmental trends in selective attention could not be
      attributed to age changes in the accessibility of dimensional structure. The
      second experiment, where the task was to focus on a central arrow stimulus and to
      ignore flanking arrows, allowed further examination of the mechanisms involved in
      developmental changes in interference effects. The primary source of the
      developmental decrease in interference from irrelevant information was found to
      be in the rate at which the output of perceptual analysis is coupled to the
      preparation and execution of a motor response, rather than in perceptual
      filtering or in response preparation. The combined results suggest that age
      changes in selective attention are mediated to an important extent by changes in
      the speed and efficiency of stimulus-response translation processes. These
      findings are discussed in terms of developmental theories of interference
      control.

PMID- 9178964
TI  - Serial recall of poor readers in two presentation modalities: combined effects of
      phonological similarity and word length.
AB  - Immediate ordered memory for words in poor readers was compared with that of two
      control groups of normal readers, matched on chronological age and reading age,
      respectively. The groups were equated for basal memory capacity. Phonological
      similarity and word length were simultaneously manipulated. Items were presented
      either auditorily (spoken words) or visually (their corresponding drawings). The
      results suggest that when having to recall a restricted set of items and when
      verbal output is eliminated, phonological coding and rehearsal occur to the same
      extent in poor and normal readers, with auditory as well as visual presentation.
      However, irrespective of presentation modality, absolute performance of the poor
      readers was still worse than that of their chronological age controls.

PMID- 9178965
TI  - Segmentation, not rhyming, predicts early progress in learning to read.
AB  - We present a longitudinal study of children in the first two years of learning to
      read. A battery of tests of phonological skills administered when the children
      were prereaders identified two distinct and relatively independent factors,
      Rhyming (defined by measures of rhyme detection and rhyme production) and
      Segmentation (defined by measures of phoneme identification and phoneme
      deletion). Segmentation was strongly correlated with attainment in reading and
      spelling at the end of the first year at school, though Rhyming was not. In
      addition, letter name knowledge predicted both reading and spelling skill and
      showed an interactive effect with children's segmentation skills. By the end of
      the second year of school, however, rhyming had started to exert a predictive
      effect of spelling, but not on reading. The results are discussed in the context
      of current theories of the role of phonological skills in learning to read.

PMID- 9178966
TI  - Expression of MAGE genes in colorectal carcinomas.
AB  - The human genes MAGE-1 and MAGE-3 encode tumor rejection antigens recognized on
      melanoma cells by cytotoxic T lymphocytes (CTL). These antigens are potentially
      useful as targets for specific immunotherapy. Expression of MAGE genes in some
      malignant tumors has been reported, but MAGE gene expression in colorectal
      carcinomas has not been studied adequately. Therefore, we studied MAGE-1,2,3, and
      4 a/4 b expression at the mRNA level, in 40 cases of surgery for colorectal
      carcinoma, using the reverse transcription polymerase chain reaction (RT-PCR).
      MAGE-1,2,3, and 4 a/4 b genes were expressed in 3 (7.5%), 6 (15.0%), 13 (32.5%),
      and 5 (12.5%), respectively, of these 40 cases. A total of 19 of the 40 samples
      (47.5%) expressed at least one of the MAGE genes. The relationships between
      clinicopathologic factors and MAGE gene expression were also examined. The
      frequency of lymph node metastasis was significantly higher in MAGE-3-positive
      than in MAGE-3-negative cases (p < 0.05). All these cases classified as Duke's D
      expressed the MAGE-3 gene. This rate of expression was significantly higher than
      that for all other the Duke's classifications together (p < 0.05). Our findings
      suggest that MAGE-specific immunotherapy against colorectal carcinomas may be
      feasible.

PMID- 9178967
TI  - [A study of the association between HLA phenotype and serum concentration of
      soluble HLA class I].
AB  - We investigated the association between the phenotypes of human leucocyte
      antigens (HLA) class I on the surface of lymphocytes and serum concentrations of
      soluble HLA (sHLA) in normal and Human immunodeficiency virus (HIV) infected
      subjects. Serum concentrations of sHLA inn normal subjects with HLA-A 24 were
      significantly higher than those in such subject without HLA-A 24. The similar
      relation was found in HIV infected subjects whose levels of sHLA significantly
      increased compared with that of normal subjects. These results might suggest that
      the mechanism which causes the increase in secretion of sHLA in HIV infected
      subjects does not change the association between HLA phenotype and serum
      concentration of sHLA.

PMID- 9178968
TI  - [Effects of fibronectin on the monokine production by cultured-human monocytes].
AB  - The effect of fibronectin (FN) on IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6
      production was investigated with cultured monocytes isolated from human
      peripheral blood. Monokine concentrations were determined by ELISA. FN markedly
      stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 from
      cultured monocytes. Northern blot analysis revealed the up-regulated expression
      of mRNA specific for each monokine on exposure of monocytes to FN. GM-CSF, IFN
      gamma, and LPS synergistically enhanced FN-induced IL-1 alpha production. We
      further investigated the signal transduction pathways involved in FN-stimulated
      monokine secretion. FN-stimulated TNF-alpha secretion was markedly inhibited by
      either herbimycin A or genistein, inhibitors of protein tyrosine kinase (PTK),
      but was not affected by staurosporin, a inhibitor of protein kinase C (PKC). The
      results suggest that PTK is required for FN-stimulated TNF-alpha secretion. In
      contrast, LPS-stimulated TNF-alpha secretion was markedly inhibited by not only
      herbimycin A or genistein, but also staurosporin. Therefore, both PTK and PKC may
      be involved in LPS-stimulated TNF-alpha secretion. We also demonstrated that, in
      monocytes, cytoplasmic proteins of about 70 and 240 kDa were phosphorylated after
      FN stimulation. Our results indicate that FN may contribute to the inflammatory
      response of monocyte by inducing monokine production.

PMID- 9178969
TI  - [An autopsy case of anti-neutrophil cytoplasmic antibodies associated vasculitis
      accompanied by autoimmune hepatitis and hepatocellular carcinoma].
AB  - Here we report an autopsy case with anti-neutrophil antibodies (ANCA) associated
      vasculitis accompanied by autoimmune hepatitis and hepatocellular carcinoma. A 69
      year-old woman was admitted to Tokyo Metropolitan Ohtsuka Hospital in October
      1995 because of leg edema. She had presented cough in 1990 and diagnosed as
      interstitial pneumonia, esophageal varices and liver chirosis. On admission,
      laboratory data showed mild anemia, hypoproteinemia, and marked gammagloblinemia.
      IgM-HA antibody, HBs antigen, HBs antibody, HCV antibody and HDV antibody were
      negative. Anti-nuclear antibody, anticentromere antibody, anti-neutrophil
      cytoplasmic antibody against myeloperoxidase and cathepsin G (MPO-ANCA and
      cathepsin G), rheumatoid factor and direct coombs test were positive. Serum level
      of AFP and CEA were elevated. Ultrasonography and computed tomography of abdomen
      scowed liver chirosis and tumor in left lobe of liver. The diagnosis of liver
      chirosis based on autoimmune hepatitis and Interstitial pneumonia was made with
      clinical course, laboratory findings and radiographic findings although liver
      biopsy was not performed. She complained of bloody stool due to ulcer of the
      large intestine, and died of liver failure which progressed rapidly. The autopsy
      findings detected that pulmonary fibrosis, liver fibrosis with multiple
      hepatocellular carcinoma, necrotizing crescentic glomerulonephritis, and
      vasculitis of small artery inn colon. This was the first report of MPO-ANCA
      associated vasuculitis complicated with autoimmune hepatitis and hepatocellular
      carcinoma. Clinical significance of ANCA and immunogenetic background of these
      diseases were discussed.

PMID- 9178971
TI  - Severe thrombocytopenia after cytomegalovirus infection in an immunocompetent
      host--correlation between CMV infection and platelet count in immunocompetent
      host.
AB  - We report a case of severe thrombocytopenia after cytomegalovirus mononucleosis
      and the changes of the platelet count in 13 cases (including documented case)
      with CMV mononucleosis (4 cases) or Epstein-Barr virus mononucleosis (9 cases),
      who were admitted to our hospital from 1991 to 1995. A decrease of the platelet
      count was observed in some patients at diagnosis compared to the following days,
      suggesting that thrombocytopenia may be induced by CMV as well as EBV, and mild
      thrombocytopenia may be more frequent than expected after CMV infection in
      immunocompetent adults, although severe thrombocytopenia is rare.

PMID- 9178970
TI  - [Remission by leukocytapheresis for a patient with ulcerative colitis found
      refractory by conventional drug therapies].
AB  - A 40-year-old male was admitted to our hospital on August 30, 1994 to receive a
      new ulcerative colitis (UC) therapy, leukocytapheresis (LCAP). On the admission
      day, he had bloody stool 5 to 6 times/day, abdominal pain, slight fever, and
      hypoproteinemia. His UC type was moderately severe left-sided colitis with
      pseudopolyposis. Prior to admission to our hospital, his condition had not
      improved for about 9 months, despite drug therapies such as
      salicylazosulphapyridine, intravenous high dose prednisolone, protease inhibitor,
      intraarterial hydrocortisone sodium succinate, 4 series of pulse therapies with
      metylpredonisolone, enema of corticosteroid, azathioprine (Imuran), and
      cyclosporine at another hospital. Thus he was introduced to our college hospital
      and treated by LCAP since September 1. After 10 LCAP sessions, remission was
      observed and the patient discharged on December 23. Until he was later operated
      on for heavy bleeding after he had discontinued treatment and had drunk heavily,
      he had maintained remission for 13 months with LCAP only once a month even after
      we gradually decreased the other medical supports and stopped all of them. After
      LCAP, the normalization of high percentage of leukocytes presented HLADR+ and
      lymphocytes presented CD 11 a+ CD 8+ was also observed. This suggests LCAP
      intercepts the excess immune reaction in UC by removing leukocytes.

PMID- 9178973
TI  - [Collagen analysis in fibroblasts in osteogenesis imperfecta. Clinical benefits].
AB  - We performed collagen analysis in 38 patients with osteogenesis imperfecta. In
      order to assess the clinical benefit of the analysis, all cases were studied
      retrospectively. Five patients were children with lethal osteogenesis imperfecta,
      in whom the diagnosis was confirmed after termination of pregnancy. In the
      remaining 33 patients, collagen analysis was performed because of clinical
      suspicion of osteogenesis imperfecta. Child abuse was suspected in seven
      patients. We found good correlation between the results of collagen analysis and
      the final diagnoses, which were based on clinical information and observation
      over time. In this study we also tested a set of diagnostic criteria which seem
      to be useful in clinical practice. The collagen analysis was of decisive
      diagnostic value in half (16/33) of the patients, but also in the remaining
      patients the clinical diagnosis was strengthened. We obtained only one false
      negative result. Our study indicates that in selected patients where diagnosis is
      difficult, collagen analysis can be an important tool in establishing the
      diagnosis osteogenesis imperfecta.

PMID- 9178972
TI  - [A case of Sjogren's syndrome associated with EDTA-dependent
      pseudothrombocytopenia].
AB  - A 69-year-old woman was admitted to Department of Orthopedic Surgery in our
      hospital because of lumbago on April 4, 1995. Since laboratory data showed
      thrombocytopenia (platelet count 2.1 x 10(4)/mm3) on admission, she was
      transferred to Department of Internal Medicine for further examination on April
      11. She noticed abnormal taste and showed remarkable sicca symptoms. Schirmer
      test, gum test and electrogustometry were positive, and parotid sialogram
      findings and histology of minor salivary glands of the lip were compatible with
      those of typical Sjogren's syndrome. Thus, she was diagnosed as Sjogren's
      syndrome. Although the antibodies to SS-A/SS-B were negative in her serum, anti
      nuclear and anti-centromere antibodies were strongly positive (x1280). Serum IgM
      level was increased. The decreased platelet count was observed when EDTA was used
      as anticoagulant. The binding activity of the anti-platelet antibody activated by
      EDTA was dependent on temperature. Its immunoglobulin class was shown to be IgM
      by enzyme-labelled antibody method. We here report a case of Sjogren's syndrome
      associated with EDTA-dependent pseudothrombocytopenia.

PMID- 9178974
TI  - Form, function and strength in the restored dentition.
AB  - The masticatory system is a biomechanical engine for the reduction of food before
      final absorption by the alimentary canal. These demands may lead to biological
      changes dominated by wear, fracture, or plastic deformation. This in turn lead to
      the loss of hard tissue, which is detrimental to the primary function of the oral
      cavity. The primary roles of restorative dentistry are to restore what is lost
      and to preserve remaining hard tissue, which is served by conservative techniques
      and the development of materials that recover the function of lost tissue. The
      criteria for new restorative materials should be based on the structure-property
      function relationships of the hard tissues. An understanding of these
      relationships may lead to better methods of assessment and provide clues for the
      development of better synthetic analogues for enamel and dentine.

PMID- 9178975
TI  - Peri-implantitis.
AB  - The anatomy of the periodontal tissues of a tooth differs from that of a dental
      implant. The largest differences are in the lack of a periodontal membrane
      between the bone and a dental implant and its lack of an organized connective
      tissue attachment at the collar. These anatomical differences may influence the
      inflammatory response of each to bacterial plaque. Similarity has been
      demonstrated between the bacterial plaque on implants and teeth, but the
      significance of the difference between plaques at healthy and diseased sites on
      implants has not been determined. The consequence of periodontitis is loss of
      fibrous tissue attachment to the tooth and loss of supporting bone. A similar
      loss of supporting bone adjacent to dental implants has also been observed.
      Regenerative surgical techniques have been developed to reform the fibrous tissue
      attachment to the tooth and replace the lost supporting bone and these techniques
      have not been applied to dental implants. Healing and regeneration after
      periodontitis is now better understood, but regeneration around implants remains
      controversial. The evidence for the existence of a distinct entity, 'peri
      implantitis', and its treatment are discussed.

PMID- 9178976
TI  - Lasers--panacea or paradox?.
AB  - The first lasers were quite unsuitable for dental use, but the last 30 years have
      seen the development of a variety of lasers which allow dentists to cut soft
      tissue without bleeding, remove caries, cut cavities in teeth (usually without
      pain), cure composite resins rapidly, weld metals with precision, desensitize
      teeth, sterilize exposed pulps and tissue surfaces and treat skin lesions. Future
      research may explain why 'soft' lasers appear to promote healing and alleviate
      joint and muscle pain. There are now many published reports in refereed dental
      journals covering the various aspects of laser dentistry. Dentists interested in
      lasers, or who are considering purchasing one should read the relevant literature
      and consult their Association and colleagues before making a purchase.

PMID- 9178977
TI  - Periodontics into the 21st century.
AB  - In recent years advances in clinical techniques and procedures such as guided
      tissue regeneration and implants, have dominated periodontics. However, as we
      move towards the 21st century, emphasis is swinging 'back to basics' with the
      recognition that patient susceptibility to periodontal disease determines the
      ultimate outcome not only of the disease process but also of the treatment
      undertaken. In this context attention is returning to the host response and with
      the advent of clonal and molecular biological techniques, new insights are being
      gained into the nature of host susceptibility. Previous studies have suggested
      that a T-cell/macrophage immunoregulatory imbalance may exist locally in the
      periodontitis lesion and that this imbalance may be antigen specific. More
      recently, T-cell subsets have been dichotomized on the basis of their cytokine
      profiles. In general, Th1 cells produce IL-2 and IFN-gamma while Th2 cells
      produce IL-4, IL-5 and IL-6. The major function of Th1 cells is to mediate
      delayed type hypersensitivity. In contrast the major function of Th2 cells is to
      provide B-cell help. A model for periodontal disease has now been developed based
      on this functional dichotomy which provides a framework for the study of cytokine
      profiles in periodontal disease. Early studies in this context have demonstrated
      higher proportions of IL-4 and IL-13 producing cells in periodontitis tissues
      together with possible variations in IL-10 production. Clonal studies have shown
      that the selection of a particular cytokine profile is not antigen dependent and
      that differences may be due to the host susceptibility although this remains to
      be determined.

PMID- 9178978
TI  - Failures, disasters and catastrophes--a hypothetical endodontics.
AB  - Failures occur in dentistry as a result of many factors some of which can be
      controlled by the operator whilst others are unavoidable. The long-term success
      rate of endodontic treatment has often been thought to be very high although
      studies reported in the literature do not support this perception. The number of
      failures can be reduced by adhering to accepted treatment procedures and by
      avoiding 'short cuts'. Recent work now points to endodontic failures being
      largely a consequence of failures of the coronal restoration rather than being
      due to failure of the root canal filling itself. Disasters are usually related to
      operator errors and they may have detrimental effects on the outcome of treatment
      in the long term, eventually becoming catastrophes. Endodontic disasters will
      require special techniques to salvage them whereas catastrophes usually result in
      loss of the tooth and every effort should be made to prevent such problems from
      occurring.

PMID- 9178979
TI  - CAD/CAM dentistry.
AB  - CAD/CAM dentistry offers numerous advantages for both patient and dentist but
      still has problems to overcome. Recently the scope, sophistication and number of
      systems has increased. This paper aims to review and compare the systems
      available and systems under development, detailing current advances in the
      prosthodontic, orthodontic and oral surgery aspects of dentistry. Areas of future
      improvement, which includes aesthetics and integration with existing computer
      uses, are also indicated. Reductions in cost and improvements in user
      friendliness are needed to see CAD/CAM more widely adopted into conventional
      dental practice.

PMID- 9178980
TI  - Infection control in practice. Infection control and clinical efficiency: are
      they compatible?
AB  - A frequently expressed concern regarding infection control guidelines is that
      they require too much time, effort and expense. This paper will address those
      concerns by examining the relationship between infection control and clinical
      efficiency. Infection control procedures can be minimized if proper attention is
      given to the concept of Limited Surface Contamination. Adherence to a clearly
      defined Zone of Contamination is essential. Emphasis should be on prevention
      rather than elimination of contamination. By following well-established
      principles of Dental Assistant Utilization (DAU), or 'four-handed dentistry',
      clinical efficiency is enhanced and infection control improved. Proper infection
      control in the dental surgery is virtually impossible without the cooperation and
      involvement of a well-trained, committed dental chairside assistant.

PMID- 9178981
TI  - Infection control in practice. Infection control--peer review.
AB  - There is increasing public and government concern about the risks of transmission
      of diseases in dentistry. This can be addressed by implementing a voluntary self
      regulatory infection control assessment process. Such a system (AMADA Quality
      Management) has been developed and implemented in South Australia and has eased
      the pressure on the Government to legislate for the establishment of minimum
      infection control standards for the dental profession. Control of these issues
      has remained with the profession an the standards achieved have been high and
      sustainable.

PMID- 9178982
TI  - Paediatric dentistry--what's new. A contemporary approach to the art and science
      of caries risk assessment.
AB  - Preventive dental care for children and adolescents has historically focused on
      fluoride therapy, oral hygiene and home care maintenance, simple dietary advice,
      and the placement of fissure sealants. Traditionally, dental caries has been
      regarded as a static phenomenon, eventuating in loss of tooth structure while the
      basis for treatment and management of this ubiquitous disease has essentially
      been mechanical. However, with current developments in new dental materials,
      techniques and preventive strategies, a more precise understanding and
      appreciation of the nature of the caries process is required. The development of
      dental caries is a common yet complex series of dynamic events under the
      influence of numerous inter-related biological, social, behavioural and
      psychological factors. It is now increasingly recognized that certain 'high risk'
      caries-susceptible individuals persist within our communities for whom preventive
      measures and restorative care alone are not enough to control the disease. This
      paper will discuss and outline current preventive concepts, individual risk
      factors, and dietary considerations which can be utilized in a contemporary
      approach to caries risk assessment.

PMID- 9178983
TI  - Paediatric dentistry--what's new. Paediatric dentistry and diet.
AB  - Many children are given so many soft, easy-to-swallow foods that they do not
      learn to chew. This affects not only their dental development but also their
      health. Up to one-third of Australian children are overweight and 50 per cent of
      10-15 year olds have high levels of serum cholesterol. It's time to encourage
      children to eat fewer soft, fatty, sugary foods and more fruits, vegetables,
      chewy breads, and grain-based foods. This paper aims to show that the diet that
      is good for children's teeth is also good for their health.

PMID- 9178984
TI  - Concepts in the management of temporomandibular ankylosis.
AB  - Temporomandibular ankylosis is a relatively rare condition in the western world
      and is usually due to trauma or infection. There is a potential for significant
      growth disturbance in the growing patient and active treatment must be undertaken
      at an early stage. Aggressive resection of the ankylosis with or without
      coronoidectomies is performed followed by growth centre transplantation and
      active postoperative physiotherapy. In the adult patient, a large-gap
      arthroplasty must be created followed by an interpositional tissue transfer such
      as a temporalis flap or an alloplastic reconstruction.

PMID- 9178985
TI  - Malar recontouring using 3D bio-modelling.
AB  - The augmentation of congenital or acquired deficiencies of the malar complex is a
      good example of how three-dimensional bio-modelling has become a useful addition
      to the modern surgeon's resources. This paper will review a range of bio
      modelling applications within our regional specialty, with particular reference
      to the options available for contour reconstruction of the malar complex.

PMID- 9178986
TI  - Options in rebuilding an alveolar ridge in the postoperative cancer patient.
AB  - Rebuilding of the alveolar ridge is part of oral rehabilitation for the
      postoperative cancer patient. Consideration should be given to immediate or
      delayed reconstruction, the use of fixed or removable prostheses, and most
      importantly the patient's prognosis and expected outcome.

PMID- 9178987
TI  - Variations in costochondral grafting of the mandibular ramus.
AB  - This paper reviews the indications for, and the biological basis of,
      costochondral grafting for mandibular condyle replacement in adults and children.
      Our approach to costochondral grafting is described and illustrated, and known
      variations in techniques are reviewed and discussed. Data from our clinical
      series of 28 grafts is summarized.

PMID- 9178988
TI  - What is the future of third molar removal? A critical review of the need for the
      removal of third molars.

PMID- 9178989
TI  - What is the future of third molar removal? A serious presentation for not
      performing the removal of third molars.
AB  - There are three causes for third molar removal: pain, anterior crowding and the
      'time-bomb' theory, which are used to justify the removal of otherwise
      asymptomatic third molars. Arguments are presented to show that these may not be
      as true as we think and perhaps we need to reconsider our whole approach to third
      molar removal. Carrying out a procedure which has a significant risk of morbidity
      without good reason is unacceptable.

PMID- 9178990
TI  - What is the future of third molar removal? Removal of impacted third molars--is
      the morbidity worth the risk?

PMID- 9178991
TI  - Malignant lesions of the lips.
AB  - As for all cancers successful treatment of carcinoma of the lip depends on early
      detection and treatment. This article describes the different types of carcinoma
      of the lip with notes on their aetiology, diagnosis, natural histories, treatment
      and prevention. The observation is made that maxillofacial surgeons are well
      placed to make an early diagnosis which leads to decreased morbidity and
      mortality.

PMID- 9178992
TI  - The role of lasers in oral and maxillofacial surgery.
AB  - This paper reviews the types of laser available for use in oral and maxillofacial
      surgery and discusses the indications, contraindications, advantages,
      disadvantages and potential hazards of their use. Preliminary reports of research
      projects into carbon dioxide laser penetration depth into mucosa and also results
      of treatment of a series of 20 patients with a variety of mucosal problems will
      be discussed.

PMID- 9178993
TI  - Ameloblastoma revisited.

PMID- 9178994
TI  - Cervical lymphadenectomy in head and neck malignancy.

PMID- 9178995
TI  - Functional reconstruction of the jaws: new concepts.
AB  - This paper describes the surgical reconstruction of the maxilla and mandible
      after ablative surgery. The methods described are original and recently developed
      with illustrative clinical data presented. Presurgical planning of the occlusion,
      titanium mesh design supporting the bone graft, and implant-borne prostheses are
      integral elements of the concepts described to achieve functional reconstruction
      of the jaws.

PMID- 9178996
TI  - Continuing education for oral and maxillofacial surgeons--new expectations.
AB  - The Continuing Education (CE) activity of all members of the Section of Oral and
      Maxillofacial Surgery (OMFS) of the Royal Australasian College of Dental Surgeons
      (RACDS) for 1994 was surveyed. There was an 78.1 per cent response rate. The
      total average CE activity was 165.9 per cent hours per year, range 0 hours to 992
      hours. This was the sum of attendance and participation in national and
      international meetings; self education and journal reading; professional
      committee activity and examining. There was also a high level of teaching, both
      undergraduate and postgraduate; examining; research; publications and
      professional committee involvement. Further analysis involved weighted scores and
      factors contributing towards low and high CE activity. Possession of the
      qualification of FRACDS (OMS) was associated with the highest level of CE. It was
      concluded that Australian and New Zealand oral and maxillofacial surgeons
      generally had a high degree of CE activity.

PMID- 9178997
TI  - The future of oral and maxillofacial surgery in the United States.
AB  - This paper explores the past, present, and future of the specialty of oral and
      maxillofacial surgery in the United States as viewed through the eyes of the
      author. Many changes have occurred over the past ten years that have changed the
      complexion of the entire health care industry. The overall effect of these
      changes is to decrease the amount of funding that will be available for our
      services. These changes have caused challenges for the specialty. How will we
      cope? Will we survive? Are we relevant? The challenges facing the specialty of
      oral and maxillofacial surgery as practised in the United States are discussed,
      and recommendations for change are put forth.

PMID- 9178998
TI  - Washington's teeth: patients' rights and dentists' rights--where are we heading?
AB  - Throughout its history in Australia the dental profession has operated primarily
      as a self-regulating profession. In recent years this paradigm has come under
      challenge from a number of quarters. Among these sources of challenge are
      Australia's various anti-discrimination laws, together with a more consumer
      oriented approach to the development of broad public policies. This paper seeks
      to explore the issues in anti-discrimination law as they relate to the balance
      between the rights of patients and the rights of dentists. The particular
      problems dealing with the treatment of patients with HIV/AIDS is explored before
      consideration is given to other issues of social justice and equity within the
      dental profession. The responsibilities of dentists as health care providers and
      as employers are considered. Some final observations are offered on the future
      developments of public policy in relation to this question.

PMID- 9179025
TI  - Purchasing. Strength in numbers.

PMID- 9179027
TI  - Quality watch ... academic health centers.

PMID- 9179028
TI  - Policy ... employers' insurance costs keep rising.

PMID- 9179029
TI  - Public health ... annual mammograms for women over 40.

PMID- 9179030
TI  - Medicare/Medicaid ... HCFA's 1997 Administrator's Award.

PMID- 9179031
TI  - Quality patrol. Worth fighting for.

PMID- 9179032
TI  - Human resources. Home is where the harm is.

PMID- 9179034
TI  - Pharmaceuticals ... all-American mom-and-pop drugstore.

PMID- 9179035
TI  - Nursing ... shortage of advanced practice nurses.

PMID- 9179036
TI  - Brand central. Interview by Chris Serb.

PMID- 9179037
TI  - This hospital for sale. Bidders for AtlantiCare Medical Center courted a tough
      customer: the community.

PMID- 9179038
TI  - Has managed care lost its soul?
AB  - Competition has transformed managed care from social movement to corporate
      colossus. In fact, the earliest health plans were founded with far more
      idealistic goals than cutting corporate America's health care tab. Here's why
      that shift troubles many managed care pioneers.

PMID- 9179040
TI  - Paid to produce. More and more CEOs are accountable for community health--with
      their paychecks.
AB  - Pioneering CEOs are backing ideals with their own money: They're linking bonuses
      to how well they improve community health. The day may be near when CEO pay
      hinges on meeting community health needs.

PMID- 9179039
TI  - Accident scenes.
AB  - Many hospital errors--including some of the most serious--never come to the
      attention of executives. A behind-the-scenes study shows how mixed incentives and
      communication snafus mask patterns of errors.

PMID- 9179042
TI  - Make vs. buy. Decision checklist.

PMID- 9179041
TI  - Speed dialing. Aiming to turn faster service into consumer loyalty, health care
      pours millions into one-stop phone centers.
AB  - Consumers want speed, convenience and efficiency when they pick up the phone to
      schedule appointments or ask questions about their health benefits. That's why
      major health care organizations are spending big to set up regional call centers.

PMID- 9179043
TI  - Medical practices. Aetna deals itself out.

PMID- 9179044
TI  - Governance. Bored meeting remedy.

PMID- 9179045
TI  - Neighborhoods. Homing in on health.

PMID- 9179046
TI  - Prisons. Going private to capture savings.

PMID- 9179047
TI  - HospitalPulse ... December 1996.

PMID- 9179048
TI  - Medicine. A doc shopper's dream.

PMID- 9179049
TI  - Pharmaceuticals. A dose of reality.

PMID- 9179050
TI  - Reengineering. Revolution in the slow lane.

PMID- 9179051
TI  - Genetic susceptibility testing. A therapeutic illusion.

PMID- 9179052
TI  - Expression of p21 (waf1/cip1/sdi1), but not p53 protein, is a factor in the
      survival of patients with advanced gastric carcinoma.
AB  - BACKGROUND: The authors examined whether expression of p21 (waf1/cip1/sdi1) and
      p53 protein was related to survival, rates in patients with advanced gastric
      carcinoma. METHODS: The expression of p21 and p53 protein was analyzed by
      immunohistochemistry in 93 patients with advanced gastric carcinoma with serosal
      invasion and lymph node metastasis. All patients underwent curative surgery. The
      probability of survival was calculated by the Kaplan-Meier method and compared by
      the generalized Wilcoxon test. RESULTS: Various levels of p21 and p53
      immunoreactivities in carcinoma cells were detected in 30 (32%) and 60 (65%),
      respectively, of 93 samples. There was no correlation between p21 and p53
      expression. The 5-year survival rate of patients with p21 expression was 69.4%,
      which was significantly better than that of patients without p21 expression
      (38.1%; P < 0.05). However, p53 protein expression did not correlate with patient
      survival. CONCLUSIONS: Expression of p21 protein may be a better prognostic
      factor than p53 protein expression in patients with advanced gastric carcinoma.

PMID- 9179053
TI  - Prognostic significance of DNA ploidy and proliferation in 309 colorectal
      carcinomas as determined by two-color multiparametric DNA flow cytometry.
AB  - BACKGROUND: Although DNA flow cytometry has been shown to be of independent value
      in determining the prognosis of colorectal carcinoma, a number of well-designed
      studies with contradictory findings have left unresolved the clinical
      significance of DNA ploidy and proliferation in biologically meaningful subsets
      of colorectal carcinoma cases. METHODS: To evaluate the prognostic significance
      of DNA ploidy and proliferation as determined by flow cytometry in a prospective
      series of 309 human colorectal carcinomas with 4-6 years of follow-up, fresh
      tumors were mechanically dissociated into whole cell suspensions and dual
      fluorescence-labeled to allow gated analysis of subpopulations with phenotypic
      markers. Software programs with histogram-dependent algorithms employing
      background, aggregate, and debris correction were used in DNA and cell cycle
      quantitation. Data were analyzed according to recommendations of the 1992 DNA
      Flow Cytometry Consensus Conference. RESULTS: None of the clinical, site, or
      staging parameters, including TNM stage variables, correlated with any flow
      cytometric DNA ploidy or proliferation measurement. Tumors classified as DNA
      aneuploid or tetraploid, by any definition, did not differ in prognosis or
      correlate with stage or any pathologic parameter. Univariate Kaplan-Meier
      survival analysis showed prognostic significance of the following: Dukes staging,
      individual components of TNM stage (tumor depth, lymph node status, and
      metastasis), vascular invasion, histologic pattern of tumor infiltration, and
      peritumoral lymphocytic inflammation. DNA ploidy status and proliferation
      measurements were not predictive of survival for the overall group or within any
      particular stage. Only Dukes Stage D (metastasis), vascular invasion, and depth
      of invasion (T classification) were significant independent predictors of
      survival in multivariate Cox regression models. CONCLUSIONS: In this analysis,
      DNA ploidy and proliferation measurements were not predictive of survival in any
      stage of colorectal carcinoma. However, clinical and pathologic documentation of
      staging and select histopathologic observations were significant predictors of
      survival in univariate and multivariate analyses.

PMID- 9179054
TI  - The safety and efficacy of transcatheter arterial chemoembolization in the
      treatment of patients with hepatocellular carcinoma and main portal vein
      obstruction. A prospective controlled study.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been contra
      indicated for the treatment of patients with hepatocellular carcinoma (HCC) and
      main portal vein (MPV) obstruction because of the potential risk of hepatic
      insufficiency resulting from ischemia after TACE. The current controlled study
      was undertaken to assess the safety, efficacy, and predictive factors of
      favorable response to TACE in patients with HCC and MPV obstruction with good
      hepatic function and adequate collateral circulation around the MPV. METHODS: Of
      a total of 47 patients, 31 were treated with TACE, and 16 who declined the
      procedures were untreated controls. Thirty-six patients (77%) had diffuse-type
      HCC and 11 (23%) had nodular-type HCC. During the first week after TACE immediate
      postprocedural complications were evaluated, and the development of hepatic
      insufficiency as a late complication was assessed at the end of the fourth week.
      The cumulative survival rate was estimated by the Kaplan-Meier method, and
      predictors of better prognosis were obtained by univariate and multivariate
      analyses. RESULTS: Although no patients showed clinical evidence of hepatic
      insufficiency as an immediate complication, transient fever and abdominal pain
      were common. Progressive hepatic insufficiency developed at the fourth week;
      however, there was no difference between the treated and untreated groups. The
      survival time of treated patients was statistically no longer than that of
      untreated patients. In the univariate analysis, tumor type and size, the pattern
      of iodized oil uptake in the tumor, and the presence of iodized oil uptake in the
      tumor thrombi at the MPV significantly influenced the prognosis. Tumor type,
      whether treated or not, was the most important prognostic factor patients with
      nodular-type HCC had significantly longer survival time (median, 11 months) than
      those with diffuse-type HCC (median, 4 months). Regarding the efficacy of TACE,
      there was no statistical difference in survival between treated and untreated
      diffuse-type HCC patients. In comparison, with nodular-type HCC it seemed that
      survival time was longer for TACE-treated patients (median, 30 months) than for
      untreated patients (median, 7 months). CONCLUSIONS: TACE may be a safe modality
      for the treatment of patients with HCC and MPV obstruction, provided that the
      patients have good hepatic function and collateral circulation around the MPV.
      However, TACE was not efficacious in the treatment of diffuse-type HCC. The
      authors recommend TACE for treating nodular-type HCC because of the potential
      benefit of prolonged survival.

PMID- 9179055
TI  - Small cell osteosarcoma of bone. Review of 72 cases.
AB  - BACKGROUND: Small cell osteosarcoma of bone is a rare form of osteosarcoma, with
      an incidence rate of 1.3%. This tumor must be differentiated from other small
      cell malignancies because of treatment considerations, particularly patient
      response to chemotherapy. METHODS: Clinicopathologic findings in 72 cases (22
      from Mayo Clinic files and 50 from consultation files) of small cell osteosarcoma
      of bone were studied. RESULTS: The femur was the most common bone involved,
      although the tumor was found in all portions of the skeleton. Radiographic
      features (available in 35 cases) suggested a diagnosis of osteosarcoma in 20
      cases, Ewing's sarcoma or lymphoma in 14 cases, and giant cell tumor in 1 case.
      Histologically, there were four types according to the predominant cell size and
      cytologic features. Osteoid production was identified in all tumors. Complete
      treatment and follow-up data were available for 45 cases. Generally, in those
      cases without surgical treatment, greater than 60% of patients died of disease
      within 2 years. If the surgical procedure was associated with a marginal tumor
      margin, the prognosis was poor. In the 30 patients with wide or radical surgical
      margins, at last follow-up 13 were alive with no evidence of disease, 2 were
      alive with disease, and 15 died of disease at 5 months to 13.1 years after
      diagnosis. In 16 of 22 Mayo Clinic patients, excluding those who presented with
      metastasis, the cumulative 5-year survival rate was 28.9%. Median survival time
      in patients who had surgery with additional chemotherapy was 13.4 years, compared
      with 1.4 years in patients who underwent surgery alone (P = 0.17). CONCLUSIONS:
      Small cell osteosarcoma is a definite reproducible histologic entity. Treatment
      should be based on a protocol for osteosarcoma.

PMID- 9179056
TI  - High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin,
      vincristine, and prednisone regimen in the treatment of patients with advanced B
      cell chronic lymphocytic leukemia. Results of an international multicenter
      randomized trial. International Society for Chemo-Immunotherapy, Vienna.
AB  - BACKGROUND: In recent years, much attention has been paid to the possible
      efficacy of intensive chemotherapy in the treatment of advanced, progressive B
      cell chronic lymphocytic leukemia (CLL) patients. For this reason, the
      International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia
      Cooperative Group, has begun a randomized multicenter trial comparing Binet's
      modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
      regimen with continuous high dose chlorambucil (HD-CLB). METHODS: During the
      period January 1987 to May 1993, 228 previously untreated CLL patients from 7
      cooperative institutions were randomized to this trial. Advanced and/or
      progressive disease was defined by high Total Tumor Mass (TTM) score (> 9),
      and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The
      response to therapy was defined by reduction of the initial TTM score. The end
      points of the trial were response rate, survival, and toxicity. RESULTS: HD-CLB
      resulted in a higher response rate than CHOP in evaluable cases, with 89.5%
      overall responses (complete response+partial response) versus 75%, respectively
      (P < 0.001). At the time of an analysis performed in July 1995 (after a median
      follow-up period of 37 months), overall survival was also longer in the HD-CLB
      treatment arm (median survival, 68 months) than in the CHOP treatment arm (median
      survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the
      two treatment arms. CONCLUSIONS: The current study showed that HD-CLB is an
      effective and well-tolerated therapeutic option for patients with advanced and/or
      progressive CLL. Therefore, the authors recommend its wider use, possibly in
      comparison with and/ or in combination with new therapeutic agents, such as
      purine analogues.

PMID- 9179057
TI  - LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant
      fibrous histiocytoma.
AB  - BACKGROUND: In this study, the authors examined the expression of LN-2, an
      antigen expressed by B cells, macrophages, and Reed-Sternberg cells, in a variety
      of spindle cell lesions of the skin to determine whether LN-2 immunoreactivity
      can be used to differentiate among these tumors. For comparison, they examined
      CD34 antigen expression in these lesions, which has been shown to be a useful
      marker in differentiating dermatofibrosarcoma protuberans from dermatofibroma.
      METHODS: Immunocytochemistry with anti-LN-2 and anti-CD34 monoclonal antibodies
      on formalin fixed, paraffin embedded material was performed on 102 spindle cell
      lesions, including dermatofibroma, dermatofibrosarcoma protuberans, atypical
      fibroxanthoma, malignant fibrous histiocytoma, leiomyoma, and neurofibroma.
      RESULTS: LN-2 immunoreactivity did not distinguish between dermatofibroma and
      dermatofibrosarcoma protuberans, both of which showed weak immunoreactivity. In
      marked contrast, 90% of cases of malignant fibrous histiocytoma showed strong
      staining for LN-2, whereas the vast majority (90%) of cases of atypical
      fibroxanthoma were negative or stained only weakly with anti-LN-2 antibodies. Of
      the two cases of atypical fibroxanthoma that stained strongly for LN-2, both
      lesions were > 2 cm in size and extended deep into the subcutaneous fat.
      CONCLUSIONS: Differential expression of the LN-2 antigen by atypical
      fibroxanthoma and malignant fibrous histiocytoma distinguishes these two lesions
      and suggests that acquisition of LN-2 positivity may be a marker of tumor
      progression.

PMID- 9179058
TI  - Malignant and benign tumors in patients with neurofibromatosis type 1 in a
      defined Swedish population.
AB  - BACKGROUND: The development of malignant and benign tumors in patient with
      neurofibromatosis type 1 (NF1) was investigated in a long term follow-up study of
      70 adult NF1 patients living in Goteborg, Sweden, on January 1, 1978. Their mean
      age at that time was 44 years (range, 20-81 years). The 70 NF1 patients had
      previously been investigated in a population-based study. METHODS: The first part
      of this study involved a cancer registry study. The authors compared the number
      of tumors in the 70 NF1 patients reported to the Swedish Cancer Registry during
      the period 1978-1989 with the number of tumors expected in the general population
      by matching the incidence rates of the two populations specific to age, time of
      follow-up, and gender. The 95% confidence interval for the risk quotient between
      the risk to the patients and the risk to the general population was estimated.
      The second part of the study was a clinical pathologic follow-up study. All
      living patients were offered a clinical reexamination in 1990. All hospital
      records for all the NF1 patients were reviewed, and death certificates were also
      reviewed when available. RESULTS: Malignant tumors were reported to the Cancer
      Registry four times as often in the NF1 patient group as in the general
      population (95% confidence interval, 2.1-7.6) during the follow-up period 1978
      1989. Before 1978, 5 of 70 patients (7%) had 6 malignant tumors; these patients
      were not included in the Cancer Registry study. Using all available clinical data
      on the 70 NF1 patients from their birth up to 1990, the authors found that 17 of
      70 patients (24%) had developed a total of 19 malignant tumors, namely, 5
      sarcomas (in 7% of patients), 13 carcinomas (in 16%), and 1 malignant melanoma
      (in 1%). Four pheochromocytomas (in 6% of patients), 2 adenomas, and 1 C-cell
      hyperplasia were diagnosed. Five gastrointestinal stromal tumors (in 7% of
      patients) were also diagnosed. CONCLUSIONS: Malignant tumors were reported to the
      Swedish Cancer Registry significantly more often in the NF1 patients than was
      expected in the general population matched for age, gender, and time of follow
      up. The development of tumors is part of the NF1 disease process, and this
      deserves attention both in the clinical setting and in family counseling dealing
      with complications of NF1 in adulthood.

PMID- 9179059
TI  - Increased cathepsin D level in the serum of patients with metastatic breast
      carcinoma detected with a specific pro-cathepsin D immunoassay.
AB  - BACKGROUND: An increased cathepsin D (cath-D) level in breast carcinoma cytosol
      has been proposed as a prognostic parameter. However, no increase had been
      previously detected in serum when assaying total cath-D concentration. METHODS:
      The authors compared 2 radioimmunoassays of total cath-D and pro-cath-D in the
      serum of 3 groups of patients: those with metastatic breast carcinomas (n = 30),
      those with nonmetastatic breast carcinomas (n = 24), and healthy women (n = 21).
      RESULTS: There was a significant increase of total cath-D and pro-cath-D in the
      serum of 18 of the 30 patients with metastatic breast carcinoma. No increase was
      observed in any of the patients with nonmetastatic disease compared with healthy
      women. Moreover, the level of pro-cath-D was often superior to that of total cath
      D in the same patients, suggesting that the total cath-D assay in serum
      underestimates the actual concentration of pro-cath-D. This is not believed to be
      due to the masking of cath-D with the circulating mannose-6-phosphate/insulin
      like growth factor II receptor because the purified receptor did not interfere in
      the binding of the monoclonal antibodies used in the assay to cath-D.
      CONCLUSIONS: An increased level of cath-D in the serum of breast carcinoma
      patients is a late event observed only in patients with metastatic disease. This
      increased circulating level is more likely due to increased secretion of the
      proenzyme rather than to tumor cell lysis.

PMID- 9179060
TI  - Response to second-line chemotherapy in patients with metastatic breast carcinoma
      previously responsive to first-line treatment: prognostic factors.
AB  - BACKGROUND: The aim of this retrospective study was to determine those prognostic
      factors associated with response to a second-line chemotherapy in patients with
      metastatic breast carcinoma (MBC) that was previously responsive to a first-line
      chemotherapy. METHODS: The 70 MBC patients studied had previously responded to a
      first-line chemotherapy, mainly anthracycline or anthracenedione-containing
      regimens. During first-line chemotherapy they had received treatment until the
      maximum response was obtained, at which time treatment was discontinued. Second
      line chemotherapy regimens were of several types (48.5% with anthracycline). A
      study of prognostic factors associated with response to second-line chemotherapy
      was performed by univariate and multivariate analysis. RESULTS: Second-line
      chemotherapy achieved a 44% response rate, with a median response duration of 10
      months. Survival was 13 months in the entire patient group, 22 months in
      responders, and 8 months in nonresponders. Univariate analysis identified seven
      factors related to patient response rate to second-line treatment. A better
      response rate to second-line chemotherapy was observed in patients with the
      following features: 1) chemotherapy free time (time between onset of metastatic
      disease and initiation of first-line) < 12 months (P = 0.03); 2) complete
      response to first-line chemotherapy (P = 0.013); 3) response duration to first
      line chemotherapy > 14 months (P = 0.0001); 4) progression free interval (time
      between end of first-line treatment and initiation of second-line chemotherapy) >
      11 months (P = 0.0001); 5) performance status at second-line treatment < 2 (P =
      0.04); 6) tumor index at second-line chemotherapy < 4 (P = 0.05); and 7)
      treatment with an anthracycline-containing second-line regimen (P = 0.03). In
      multivariate analysis, only progression free interval was identified as being
      associated with response rate to second-line chemotherapy (P = 0.0001).
      CONCLUSIONS: Retained chemosensitivity appeared to be an important characteristic
      in patients responding to second-line chemotherapy.

PMID- 9179061
TI  - Immunohistochemically detected p53 and HER-2/neu expression and nuclear DNA
      content in familial epithelial ovarian carcinomas.
AB  - BACKGROUND: Some epithelial ovarian carcinomas tend to occur more frequently in
      certain families. This clustering may be due to a genetic predisposition, but the
      role of inherited susceptibility in all families with multiple cases of ovarian
      carcinoma is currently unresolved. Studies characterizing familial ovarian
      carcinomas are few. METHODS: From a population-based study of 559 patients with
      epithelial ovarian carcinoma, 27 families with 2 or more ovarian carcinoma cases
      occurring in first-degree relatives were identified. Histopathology, ploidy, and
      immunohistochemically detected p53 and HER-2/neu expression in these tumors were
      examined. RESULTS: The mean age of the patients with familial ovarian carcinoma
      was 56.7 years. Approximately 67% of the tumors were either serous or
      undifferentiated adenocarcinomas. The percentage of aneuploid tumors was 46%,
      that of p53 positive tumors was 51%, and that of HER-2/neu positive tumors was
      69%. When the families were divided into families with cases of breast carcinoma
      in addition to ovarian carcinoma cases and/or ovarian carcinoma in 2 consecutive
      generations (12 families) and families with ovarian carcinoma occurring in
      sisters only without cases of breast carcinoma (15 families), no differences were
      noted in the frequency of any of the studied variables. CONCLUSIONS: Familial
      ovarian carcinomas do not appear to differ from sporadic ovarian carcinomas with
      regard to patient age at presentation, histopathology, ploidy, and
      immunohistochemically detected p53 expression. Immunohistochemically detected HER
      2/neu expression was found to occur more frequently in familial ovarian
      carcinomas than has been reported in sporadic ovarian carcinomas.

PMID- 9179062
TI  - An enhanced prognostic system for clinically localized carcinoma of the prostate.
AB  - BACKGROUND: This investigation was conducted to develop an enhanced prognostic
      system based on readily available and independently predictive tumor-related
      factors for patients with clinically localized prostate carcinoma. METHODS: The
      outcome of 500 patients treated solely with irradiation for clinical TNM
      classifications T1-4, NO or NX, MO prostate carcinoma was used to identify
      factors independently associated with disease relapse. Logistic regression
      constructed a risk score equation, and optimized cutoff points to characterize
      patient groups with low, intermediate, or high risks for relapse were established
      with receiver operating characteristic curve analysis. RESULTS: Clinical tumor
      stage (P < 0.00001), Gleason score (P = 0.0002), and pretherapy serum prostate
      specific antigen (P < 0.00001) were independently associated with clinical or
      biochemical relapse. These factors were included in a risk score equation that
      defined patient groups with a distinctly different outcome. For the low,
      intermediate, and high risk groups, the relapse-free probabilities at 5 years
      after irradiation were 92%, 67%, and 24%, respectively (P < 0.00001).
      CONCLUSIONS: Readily available, pretherapy disease-related characteristics formed
      the basis of an enhanced prognostic system for patients with clinically localized
      prostate carcinoma. A multivariate prognostic system of this nature estimated
      patient prognosis in a more exacting fashion than a system exclusively based on
      anatomic factors.

PMID- 9179063
TI  - Prognostic significance of HER-2/neu gene amplification status by fluorescence in
      situ hybridization of prostate carcinoma.
AB  - BACKGROUND: HER-2/neu gene amplification, established as a prognostic factor in
      breast carcinoma and other cancers, has not been correlated with outcome in
      prostate carcinomas (PCs). METHODS: HER-2/neu gene amplification was determined
      by automated fluorescence in situ hybridization (FISH) using a unique sequence
      cosmid probe on 113 formalin fixed, paraffin embedded 4-microns tissue sections
      and the results compared with tumor grade, DNA ploidy, HER-2/neu protein
      expression by immunohistochemistry (IHC), serum prostate specific antigen,
      pathologic stage, and postoperative disease recurrence (mean follow-up of 44
      months). RESULTS: HER-2/neu gene amplification by FISH (41% of PCs) correlated
      with tumor grade (P = 0.001) and DNA ploidy status (P = 0.0003). HER-2/neu
      protein overexpression by IHC (29% of PCs) correlated with grade (P = 0.03), but
      not with DNA ploidy. A trend for similar HER-2/neu status in each PC by IHC and
      FISH did not reach statistical significance (P = 0.25). On univariate analysis,
      HER-2/neu amplification by FISH (P = 0.029), tumor grade (P = 0.013), and DNA
      ploidy (P = 0.016) correlated with postoperative disease recurrence. HER-2/neu
      expression by IHC did not correlate with outcome. On multivariate analysis, grade
      (P = 0.0001) and ploidy (P = 0.001) were independent outcome predictors; HER
      2/neu amplification by FISH reached near-independent significance (P = 0.125).
      CONCLUSIONS: HER-2/neu gene amplification by FISH on archival PCs significantly
      correlates with grade and DNA ploidy status, is more sensitive than IHC in
      detecting HER-2/neu gene abnormalities, predicts postoperative disease
      recurrence, and may prove important in planning therapy for patients with
      prostate carcinoma.

PMID- 9179064
TI  - Predictors of mortality from kidney cancer in 332,547 men screened for the
      Multiple Risk Factor Intervention Trial.
AB  - BACKGROUND: The authors examined predictors of mortality from kidney cancer in
      332,547 men who were screened as part of the Multiple Risk Factor Intervention
      Trial. METHODS: The vital status of each member of this cohort was ascertained
      through 1990. Death certificates were obtained from state health departments and
      coded by a trained nosologist. Three hundred ninety-eight deaths due to kidney
      cancer occurred among the cohort of 332,547 men after an average of 16 years of
      follow-up. The authors used the Cox proportional hazards model to study the joint
      associations of age, race, income, blood pressure, cigarette smoking, and use of
      medication for diabetes with risk of death from kidney cancer. RESULTS: The
      authors observed independent associations with age, cigarette smoking status
      (relative risk [RR] = 2.02; 95% confidence interval [CI], 1.65-2.48), and
      systolic blood pressure (relative risk [RR] = 1.12 for systolic blood pressure
      level 10 millimeters of mercury higher; 95% CI, 1.06-1.18). The authors obtained
      similar results when deaths that occurred during the first 5 years were excluded.
      CONCLUSIONS: These findings add to the increasing body of evidence that cigarette
      smoking and blood pressure level are modifiable risk factors for kidney cancer in
      men.

PMID- 9179065
TI  - Overexpression of p53 in transitional cell carcinoma of the renal pelvis and
      ureter. Relation to tumor proliferation and survival.
AB  - BACKGROUND: Clinical management of patients with tumors of the upper urinary
      tract is based mainly on histologic grade and stage of the tumors. In recent
      years, tumor proliferation has also proved to be an important factor in
      determining the prognosis of these and other transitional cell tumors. The aim of
      this study was to assess the role of p53 in regulating cell proliferation and
      tumor progression and to define its value in predicting the long term survival of
      patients with these tumors. Such information could be of use in selecting
      treatment in individual cases. METHODS: Eighty-three patients with urothelial
      tumors of the renal pelvis and ureter diagnosed and treated between 1975 and 1993
      were included in this study. p53 immunostaining was performed on paraffin
      embedded tissue. Tumor location, histologic grade, histologic pattern, tumor
      proliferation by Ki-67, local (T classification), lymph node (N classification),
      vascular and perineural invasion, and clinical stage (TNM) were assessed in
      relation to p53 overexpression (Mann-Whitney U test and analysis of variance
      comparisons) and as prognostic factors for survival in both univariate analysis
      (log rank test) and multivariate analysis (Cox proportional hazards model).
      RESULTS: Overexpression of p53 was related to tumor proliferation as assessed by
      Ki-67 (P < 0.01), T classification (Ta vs. T1-4; P < 0.01), N classification (P <
      0.054), and TNM staging (Stage 0 vs. I-IV; P < 0.01). There was also a
      statistically significant relation to vascular (P < 0.002) and perineural
      invasion (P < 0.04). Fifteen-year actuarial survival for the whole group was 75%.
      Patients having tumors with low p53 overexpression (< 30% of stained nuclei) had
      a better survival rate (88%) than those having tumors with high (> 30%) p53
      overexpression (65%) (P < 0.02), and this effect reached statistical significance
      with high grade (P < 0.02) and infiltrating tumors (P < 0.04). Patients with low
      p53 and Ki-67 expression had a 15-year survival rate of 100%; in contrast,
      patients with overexpression of both markers had a 15-year survival rate of 61%
      (P < 0.003). In a multivariate analysis, only T classification (P < 0.001) and
      p53-Ki-67 expression (P < 0.026) were statistically significant. CONCLUSIONS:
      Overexpression of p53 is related to increased tumor proliferation and disease
      progression and is of value in determining the long term survival of patients
      with tumors of the renal pelvis and ureter. p53 immunostaining can be used to
      distinguish low risk patients in the theoretically unfavorable high grade, high
      stage group, and when used together with Ki-67 index, it is a predictive factor
      for survival.

PMID- 9179066
TI  - Selected micronutrient intake and thyroid carcinoma risk.
AB  - BACKGROUND: Protection from thyroid carcinoma due to certain dietary factors was
      suggested by several studies, but the findings were relatively inconsistent. The
      role of micronutrients has not yet been systematically analyzed. To investigate
      the relationship between micronutrient intake and thyroid carcinoma risk, the
      authors used data from a case-control study conducted in northern Italy between
      1986 and 1992. METHODS: The study included 399 incident, histologically confirmed
      thyroid carcinoma cases and 617 controls admitted to the hospital for acute,
      nonneoplastic, nonhormone-related diseases. RESULTS: Retinol intake showed a
      direct association with thyroid carcinoma risk, with odds ratios (ORs) of 1.39
      (95% confidence Interval [CI], 0.9-2.0) in the third quartile of consumption and
      1.52 (95% CI, 1.0-2.3) in the highest quartile, whereas beta-carotene had an
      inverse relationship, with ORs of 0.63 (95% CI, 0.4-0.9) in the third quartile of
      consumption and 0.58 (95% CI, 0.4-0.9) in the highest quartile compared with the
      lowest quartile. Some protection was observed for measures of vitamin C intake
      (with an OR of 0.72) and vitamin E (with an OR of 0.67) for the highest quartile
      of consumption, although the estimates were not statistically significant, and
      were reduced after adjustment for beta-carotene intake. No clear pattern in risk
      appeared for vitamin D, lolate, calcium, thiamin, or riboflavin. The inverse
      relationship between beta-carotene and thyroid carcinoma was observed in both
      papillary and follicular carcinomas. CONCLUSIONS: In this study, a significant
      inverse association between beta-carotene and thyroid carcinoma was observed, and
      some protection against thyroid carcinoma from vitamins C and E was also
      suggested.

PMID- 9179068
TI  - Diagnostic and prognostic value of nucleolar organizer regions in normal
      epithelium, dysplasia, and squamous cell carcinoma of the oral cavity.
AB  - BACKGROUND: Nucleolar organizer regions (AgNORs) are associated with
      proliferative activity and represent a diagnostic aid and prognostic marker in
      several neoplastic entities. METHODS: Sections from 51 T1-2 squamous cell
      carcinomas (SCC), 20 cases of dysplasia, and 8 specimens with normal epithelium
      were evaluated by 2 AgNOR counting methods: 1) the mean number of AgNORs per
      nucleus (mAgNOR) and 2) the percentages of nuclei with > 1, > 2, > 3, and > 4
      AgNORs (pAgNOR > 1, pAgNOR > 2, pAgNOR > 3, and pAgNOR > 4, respectively).
      RESULTS: Both mAgNOR and pAgNOR counts enabled significant discrimination between
      normal epithelium and dysplasia (P < 0.0003) and between dysplasia and SCC (P <
      0.0001). For SCC, no correlation was found between AgNOR counts and clinical
      classification. Univariate analysis using the log rank test showed that the
      overall means for mAgNOR and pAgNORs correlated with the disease free period and
      survival time (P < 0.0040). Patient age, gender, type of treatment, and T and N
      classification failed to predict the outcome. Multivariate analysis showed that
      pAgNOR > 1 (cutoff level of 88%) was the best discriminator regarding the disease
      free period and survival time (P = 0.0001 and P = 0.0076, respectively).
      CONCLUSIONS: AgNOR enumeration, in particular pAgNOR > 1, appears to be a useful
      tool in distinguishing between normal epithelium, dysplasia, and SCC of the oral
      cavity. In this study, AgNOR counts were strong prognostic markers for patients
      with SCC.

PMID- 9179067
TI  - A randomized trial of a nonabsorbable antibiotic lozenge given to alleviate
      radiation-induced mucositis.
AB  - BACKGROUND: The objective of this study was to determine whether a nonabsorbable
      antibiotic lozenge could alleviate radiation-induced oral mucositis. METHODS:
      Patients scheduled to receive radiation therapy to more than one-third of the
      oral cavity mucosa were selected for the study. After stratification, patients
      were randomized to receive either a nonabsorbable antibiotic lozenge or a
      placebo. Both groups were then evaluated for mucositis by health care providers
      and self-report instruments. RESULTS: Fifty-four patients were randomized to
      receive the antibiotic lozenge and 58 to receive the placebo. There were no
      substantial differences or trends in mucositis scores between the two study arms
      as measured by the health care providers. However, the mean patient-reported
      mucositis score and the duration of patient-reported Grade 3-4 mucositis were
      both lower in the patients randomized to the antibiotic lozenge arm (P = 0.02 and
      0.007, respectively). CONCLUSIONS: This prospective, controlled trial provides
      evidence to suggest that a nonabsorbable antibiotic lozenge can decrease patient
      reported radiation-induced oral mucositis to a modest degree. Nonetheless, this
      evidence does not appear to be compelling enough to recommend this treatment as
      part of standard practice.

PMID- 9179069
TI  - The increase of Hodgkin's disease incidence among young adults. Experience in
      Connecticut, 1935-1992.
AB  - BACKGROUND: Recent studies have indicated an increase in young adulthood
      Hodgkin's disease incidence, particularly among females, since 1970. However, no
      studies have examined the long term trends and period-cohort patterns of
      Hodgkin's disease incidence. METHODS: The current study reported time trends and
      age-period-cohort patterns of Hodgkin's disease incidence during the period 1935
      1992, with an emphasis on incidence rate changes among young adults, using data
      from the Connecticut Tumor Registry. RESULTS: A total of 4997 incidences of
      Hodgkin's disease were included in the study. The authors found that the
      incidence of Hodgkin's disease had increased among young adults age 20-44 years.
      Incidence had increased dramatically among females since 1970 but less
      significantly among males. These observed trends were primarily associated with
      nodular sclerosis histologic type. Age-period-cohort analyses indicated that
      these observed increases in young adults were cohort phenomena, suggesting
      possible changes in exposure to risk factors. CONCLUSIONS: Currently identified
      major risk factors, including social status, Epstein-Barr virus infection, and
      human immunodeficiency virus infection, cannot adequately explain the observed
      trends. Analytical epidemiologic studies are urgently needed to identify risk
      factors that will not only elucidate the etiology of Hodgkin's disease but also
      explain the rapid increase in Hodgkin's disease incidence among young females.

PMID- 9179070
TI  - A descriptive study of BRCA1 testing and reactions to disclosure of test results.
AB  - BACKGROUND: The identification of the BRCA1 gene is a powerful tool for
      predicting a patient's lifetime risk for carcinoma of the breast and ovary when
      she has hereditary breast/ovarian carcinoma (HBOC) syndrome. The process of BRCA1
      testing and genetic counseling and participants' reactions to test results, are
      described. METHODS: Education about the natural history of HBOC syndrome and the
      pros and cons of genetic testing was provided to 14 HBOC families comprised of
      2549 bloodline relatives. Of these, 388 underwent DNA testing. After informed
      consent was given by participants, formal linkage analysis and gene mutation
      studies were performed on the families. Qualitative data on intentions and
      emotional reactions were collected by physicians/counselors during the genetic
      counseling sessions. RESULTS: Of those tested, 181 received their results after
      further genetic counseling. Seventy-eight of them were positive and 100 were
      negative for BRCA1 gene mutation. Three had ambiguous findings. The most common
      reasons given for seeking DNA testing were concern about risk to children and
      concern about surveillance and prevention. Prophylactic mastectomy was considered
      by 35% of women who tested positive, whereas prophylactic oophorectomy was
      considered an important option by 76%. Twenty-five percent of both BRCA1 positive
      and negative individuals were concerned about discrimination by insurance
      companies. Eighty percent of those who tested negative reported emotional relief,
      whereas over one-third of those who tested positive reported sadness, anger, or
      guilt. CONCLUSIONS: DNA testing of patients with HBOC syndrome must be performed
      in the context of genetic counseling. The authors' results demonstrate the many
      complex clinical and nonclinical issues that are important in this process.

PMID- 9179071
TI  - Clear cell adenocarcinoma of the vagina and cervix. An update of the central
      Netherlands registry showing twin age incidence peaks.
AB  - BACKGROUND: The objective of this study was to update the registry of women in
      the Netherlands with clear cell adenocarcinoma (CCAC) of the cervix or vagina
      with or without intrauterine exposure to diethylstilbestrol (DES). METHODS: From
      a nationwide search in PALGA, the automated pathology registry in the
      Netherlands, data were gathered on women with CCAC born after 1947. Information
      obtained from the clinical files of the patients included reported exposure to
      DES, patterns of complaints previous to diagnosis, the current status of the
      patients, and the results of cytopathologic examinations previous to
      histopathologic diagnosis. After review of the histopathologic slides, the
      specific pathologic characteristics of CCAC were determined. The age distribution
      of women born after 1947 was compared with that of women born before 1947.
      RESULTS: Information about possible exposure to DES during pregnancy was
      available for 73 of 88 women with CCAC born after 1947. Exposure to DES was
      reported for 47 (64%) of these women. The DES medication was most often reported
      as having started before the 18th week of pregnancy. Cytopathologic examination
      was informative in 81% of the cases of CCAC of the cervix, but only in 41% of the
      cases of CCAC of the vagina. Most patients had Stage I or II tumors at diagnosis.
      Tumor Stage III and IV and a high grade of nuclear atypia were related to
      unfavorable outcome. The age distribution of all patients with CCAC showed two
      distinct peaks; one at young age, (a mean age of 26 years), and one at older age
      (a mean age of 71 years). This bimodal age distribution still applied when the
      cases in which DES exposure was reported had been excluded. CONCLUSIONS: Despite
      the fact that DES has not been prescribed to pregnant women in the Netherlands in
      the last 20 years, CCAC is still relevant in our times. It is important to stay
      alert and periodically to update and evaluate the data of this registry,
      including data on women born outside the DES exposure period. The bimodal age
      distribution in this study of women without intrauterine exposure to DES suggests
      a carcinogenesis-promoting role of menarche and menopause and/ or the existence
      of a subpopulation with genetic risk factors or exogenous risk factors other than
      exposure to DES. Postmenopausal observation of women exposed to DES must be
      encouraged for clinical reasons and may help facilitate differentiation between
      these two hypotheses. If these risk factors of CCAC were better documented and
      their interrelationships better defined, CCAC could become an important model of
      multistep carcinogenesis in tissues sensitive to sex hormones.

PMID- 9179072
TI  - Dihydro-5-azacytidine in malignant mesothelioma. A phase II trial demonstrating
      activity accompanied by cardiac toxicity. Cancer and Leukemia Group B.
AB  - BACKGROUND: Malignant mesothelioma is a disease that is refractory to
      chemotherapy. Therefore, the objective of this multi-institutional, cooperative
      group Phase II trial was to determine the efficacy of dihydro-5-azacytidine
      (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma.
      METHODS: Forty-one patients with histologically confirmed malignant mesothelioma
      received 120-hour continuous infusions of DHAC (1,500 mg/m2/day every 21 days)
      until maximal response, intolerable toxicity, or disease progression. RESULTS:
      One patient had a complete response, two had objective partial responses, and
      four had regression of evaluable disease. The overall response rate was 17%. The
      one complete responder remains without disease progression at 6 years. Chest pain
      and nausea were the most common toxicities. Supraventricular tachycardia and
      pericardial effusion occurred in 20% and 15% of patients, respectively. In most
      patients, gastrointestinal effects were manageable. There was no significant
      hematologic toxicity. CONCLUSIONS: In malignant mesothelioma, a disease that is
      refractory to chemotherapy, dihydro-5-azacytidine has definite antitumor
      activity. Its modest hematologic toxicity profile favors its use in combination
      with other agents. Caution regarding cardiac arrhythmias and pericardial effusion
      is necessary.

PMID- 9179074
TI  - Intraoperative electron irradiation in the management of pediatric malignancies.
AB  - BACKGROUND: External beam irradiation (PBRT), especially in children, is limited
      by the radiosensitivity of normal tissues. Local control remains a problem in
      abdominopelvic childhood malignancies. Intraoperative electron irradiation
      (IOERT) has the potential to increase the dose to the tumor, thereby improving
      local control, without increasing treatment morbidity. METHODS: Between February
      1983 and October 1990, 11 children received IOERT as part of a multidisciplinary
      treatment program for locally advanced primary or recurrent abdominopelvic
      malignancies. The 7 boys and 4 girls ranged in age from 2-18 years. Tumor
      histologies included four neuroblastomas, two desmoid tumors, and one each of the
      following: embryonal rhabdomyosarcoma, synovial cell sarcoma, neurofibrosarcoma,
      malignant fibrous histiocytoma, and paraganglioma. Single radiation doses of 10
      25 grays were delivered using 6-15-megaelectron volt electron beams to 1-5 IOERT
      fields. All patients also underwent EBRT and six received chemotherapy. RESULTS:
      Eight patients (73%) were alive and disease free at a median follow-up of 99
      months (range, 37-126 months). All eight patients who underwent gross total
      resection were locally controlled. Three patients required surgical intervention
      for IOERT-related complications and two patients developed neuropathies.
      CONCLUSIONS: IOERT as part of a multidisciplinary treatment approach in patients
      with locally advanced pediatric malignancies appears to enhance local control in
      those patients in whom a gross total resection is possible. The long term
      survival rate was encouraging. Further study, with a larger number of patients,
      appears warranted to more carefully delineate the efficacy and tolerance of IOERT
      in the pediatric population.

PMID- 9179073
TI  - Is primitive neuroectodermal tumor of the kidney a distinct entity?
AB  - BACKGROUND: Primitive neuroectodermal tumors (PNETs) constitute a family of
      neoplasms of presumed neuroectodermal origin, most often presenting as bone or
      soft tissue masses in the trunk or axial skeleton in adolescents and young
      adults. As a soft tissue neoplasm, PNET arising in the kidney has not been well
      described, with only three cases previously reported. METHODS: Four patients with
      PNET of the kidney were diagnosed and treated at St. Jude Children's Research
      Hospital. The authors reviewed the clinical, radiologic, and pathologic features
      and outcomes of these cases and of those previously described. RESULTS: The
      authors' patients were age 4-20 years. They presented with unilateral renal
      masses and metastatic disease in the lymph nodes (three patients), lungs (three
      patients), bone (two patients), liver (one patient), and bone marrow (one
      patient). Treatment included surgery, radiotherapy, and multiagent chemotherapy.
      Three of the patients died of progressive disease within 14 months of diagnosis.
      Features and outcomes were similar to those of the three previously reported
      cases. CONCLUSIONS: PNET of the kidney appears to be a distinct entity. Although
      rare, it must be included in the differential diagnosis of renal tumors in
      children and young adults. Patients usually present with advanced disease and
      show poor response to combined-modality therapy.

PMID- 9179075
TI  - Treatment of isolated testicular recurrence of acute lymphoblastic leukemia
      without radiotherapy. Report from the Dutch Late Effects Study Group.
AB  - BACKGROUND: The isolated recurrence of testicular leukemia in boys with acute
      lymphoblastic leukemia (ALL) is considered to be an ominous sign, heralding
      generalized recurrence. In general, treatment is comprised of systemic
      retreatment and local radiotherapy to one or both affected tests. METHODS: In
      this study, the authors report five boys with a late isolated testicular
      recurrence of ALL during sustained bone marrow remission, in whom radiotherapy
      had been omitted. High dose methotrexate was included in the treatment regimen.
      RESULTS: No further recurrences occurred after cessation of therapy. The follow
      up period ranged from 1-15 years (median, 8 years). CONCLUSIONS: These cases show
      that there is a subpopulation of boys with recurrence of testicular leukemia who
      can be treated without radiotherapy. Therefore, the authors propose a treatment
      regimen for boys with late isolated recurrence of testicular leukemia in which
      conventional reinduction maintenance treatment is given in combination with high
      dose methotrexate. Radiotherapy should be withheld until subsequent testicular
      recurrence occurs.

PMID- 9179076
TI  - Extramedullary acute promyelocytic leukemia.

PMID- 9179077
TI  - Pharmacoeconomic profile of paclitaxel as a first-line treatment for patients
      with advanced ovarian carcinoma. A lifetime cost-effectiveness analysis.

PMID- 9179078
TI  - Skin ulceration potential of paclitaxel in a mouse skin model in vivo.

PMID- 9179079
TI  - The National Cancer Advisory Board. 25 years later.

PMID- 9179080
TI  - RE: GR Cumming. The independent medical examination: cardiology assessment. 1996;
      12:1245-52.

PMID- 9179081
TI  - RE: GR Cumming. The independent medical examination: cardiology assessment. 1996;
      12:1245-52.

PMID- 9179082
TI  - Atrial diagnostics in a tiered therapy implantable defibrillator.
AB  - Dual chamber sensing has been proposed in implantable defibrillators as an
      additional diagnostic modality for enhanced differentiation of ventricular and
      supraventricular tachycardias. A patient with different rates of wide QRS complex
      tachycardias is described in whom a tiered therapy implantable defibrillator with
      atrial sensing capability was implanted. Atrial diagnostic data in this patient
      enabled definitive diagnosis of his ventricular tachycardias and guided
      management decisions of his arrhythmia.

PMID- 9179083
TI  - Ventricular arrhythmias in myocardial hypertrophy of various origins.
AB  - It has not been explained whether the etiological substrate of left ventricular
      hypertrophy has any influence on prevalence and severity of ventricular
      arrhythmias. Therefore, 48 h ambulatory electrocardiographic monitoring findings
      were compared in two groups of untreated patients without coronary artery disease
      and with no significant differences in age, sex, maximal and average myocardial
      thickness and left ventricular systolic function. Group A comprised 42 patients
      with pressure overload hypertrophy due to essential hypertension, and group B
      comprised 42 patients with hypertrophic cardiomyopathy. The prevalence of complex
      ventricular arrhythmias (Lown 3a-4b) was high in both groups (65% versus 60%,
      respectively, not significant). No significant difference was found in total
      frequency of most serious arrhythmias: Lown 4a, 26 versus 21 events (not
      significant), and Lown 4b, 20 versus 28 events (not significant). There was a
      correlation between prevalence of complex ventricular arrhythmias and maximal
      myocardial thickness in both groups of patients (P < 0.05), and, in group A only,
      between prevalence of complex ventricular arrhythmias and age (P < 0.01). It was
      concluded that, although the etiology of pressure overload hypertrophy of the
      left ventricle and that of hypertrophic cardiomyopathy are completely different,
      the overall prevalence and spectrum of ventricular arrhythmias in both types of
      hypertrophy are identical.

PMID- 9179084
TI  - Radiation safety in the cardiac catheterization laboratory.
AB  - Over the years, permissible radiation exposure of operators working with x-ray
      equipment has become progressively reduced. The number of cardiac
      catheterizations and related interventional procedures has increased and the
      procedures have become more prolonged. The patient receives relatively infrequent
      primary radiation while the operator receives frequent but mainly secondary
      radiation. The operator uses protective barriers, correct positioning of the
      patient and careful techniques to reduce radiation exposure. The effects of
      radiation are cumulative and permanent. They may be stochastic or nonstochastic,
      and somatic and/or genetic, and onset may be delayed for many years. To minimize
      exposure of patient and operator, cardiologists need a better understanding of
      radiation physics and of cardiac x-ray equipment. Technical breakthroughs such as
      digital imaging, pulse fluoroscopy, reduction of frame rates from 60 or 30
      frames/s to 15 frames/s, and progression to the filmless laboratory will
      substantially reduce radiation. This review discusses current cardiac x-ray
      equipment, possible future developments, radiation, and techniques for reducing
      radiation and improving safety in the cardiac catheterization laboratory.

PMID- 9179085
TI  - Comparison of Neoral and Sandimmune cyclosporine for induction of
      immunosuppression after heart transplantation.
AB  - OBJECTIVE: To compare the efficacies of Neoral cyclosporine (N-CSA [Sandoz]) and
      Sandimmune cyclosporine (S-CSA [Sandoz]) in induction of immunosuppression
      immediately after heart transplantation. DESIGN: A prospective and a
      retrospective cohort. SETTING: Patients who underwent heart transplant operations
      at the Montreal Heart Institute, Montreal, Quebec. PATIENTS: To evaluate the
      results of both formulations of cyclosporine (CSA), a cohort of 20 consecutive
      patients who underwent heart transplant operations between 1994 and 1995, and who
      were administered N-CSA, azathioprine, prednisone and intravenous CSA (10
      patients) or rabbit antithymocyte globulin (RATG) (10 patients) were compared
      with 21 patients who underwent heart transplant operations between 1993 and 1994,
      and were treated with RATG, S-CSA, azathioprine and prednisone. Preoperative
      patient characteristics were similar in all groups. RESULTS: There were no
      significant differences in daily CSA doses after the fourth day following
      transplantation. Higher trough levels of CSA were observed during the first four
      days, from days 12 to 14 and one month after transplantation in the two groups
      that were administered N-CSA. Serum levels of creatinine were significantly
      higher three to five days after transplantation in both groups who received N
      CSA. Creatinine levels were also higher between days 13 and 14 in patients who
      received N-CSA and intravenous CSA. Oral administration of N-CSA was stopped
      temporarily in two patients (20%) who received intravenous CSA because of a
      sudden decrease in urine output and rise in serum creatinine. Three months after
      transplantation actuarial freedom rate from acute rejection averaged 33 +/- 10%
      in the S-CSA group, 10 +/- 9% in patients treated with N-CSA and intravenous CSA
      and 24 +/- 15% in patients treated with N-CSA and RATG (P = 0.25). The risk
      (hazard) of early rejection was higher in the group that received intravenous CSA
      and N-CSA. CONCLUSIONS: While similar averaged doses of N- and S-CSA were
      administered early after transplantation, the use of N-CSA resulted in higher
      blood levels of CSA. N-CSA appears to be well absorbed early after cardiac
      transplantation, but renal toxicity remains a significant concern.

PMID- 9179086
TI  - The epidemiology of acute myocardial infarction and ischemic heart disease in
      Canada: data from 1976 to 1991.
AB  - OBJECTIVE: To present national trends in mortality rates for myocardial
      infarction and cardiovascular disease. DESIGN: Observational study using
      mortality statistics and hospital separation data from Statistics Canada for the
      period 1976 to 1991. RESULTS: Despite ageing of the population, there has been a
      substantial decrease in the number of deaths attributed to ischemic heart
      disease, from 51,000 in 1976 to 44,000 in 1991, with most of the decrease due to
      fewer deaths from myocardial infarction. Although age-adjusted death rates remain
      higher for men, the observed mortality decline has been more pronounced in men
      than in women. Age-adjusted separation rates have also decreased, suggesting a
      decrease in the incidence of myocardial infarction, particularly in the 45 to 64
      year age group. The duration of hospital stay has shortened dramatically.
      CONCLUSIONS: From 1976 to 1991, mortality rates for ischemic heart disease in
      Canada decreased sharply, suggesting that advancements observed in clinical
      trials are being translated to the population level. The decrease appears to be
      due to both preventive measures and improved hospital care, but further studies
      are necessary to define better the relative contribution of each factor. The
      extent of this progress over the past 15 years is similar to the American
      experience.

PMID- 9179087
TI  - Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation
      with normal left ventricular function.
AB  - Mitral regurgitation (MR) is a common, frequently asymptomatic valvulopathy that
      can ultimately lead to left ventricular failure. With the objective of
      forestalling MR progression, a prospective, placebo controlled, double-blind
      study was conducted. It measured the effectiveness of lisinopril, an angiotensin
      converting enzyme inhibitor, in reducing the echocardiographic signs of MR
      severity over a one-year period. Severe coronary disease was excluded by stress
      echocardiography. Treatment effectiveness was estimated to be proportional to the
      reduction in MR fraction and cardiac chamber dimensions, compared with baseline,
      according to intention-to-treat analysis. A final patient population of 23
      asymptomatic adults aged 53.3 +/- 2.4 years (mean +/- SEM), with moderate,
      organic MR and normal left ventricular function was selected from the
      echocardiographic database. All baseline patient characteristics were comparable
      in the two treatment groups, including the MR fraction (55 +/- 3%). Twelve
      patients received lisinopril (18 +/- 1 mg) and 11 received placebo. After one
      year of treatment, a statistically significant difference in the MR fraction was
      observed between the two groups. For the lisinopril group the MR fraction dropped
      by 6.4 +/- 3.5% and for the placebo group it increased by 3.7 +/- 3.2% versus
      baseline (P < 0.05). No differences in left atrial or ventricular dimensions were
      observed. The study drug was stopped in four patients after one patient presented
      with rapid atrial fibrillation and angina while three patients were intolerant to
      lisinopril. Only one patient receiving placebo was taken off therapy. In
      conclusion, treatment with lisinopril indicates some reduction in the severity of
      chronic moderate MR in asymptomatic patients with normal left ventricular
      function. This approach appears to be safe, but side effects are not uncommon,
      warranting regular follow-up.

PMID- 9179088
TI  - The Hemopump as a left ventricular assist device in pediatric applications:
      initial Canadian applications.
AB  - Three children aged 11 months, and eight and nine years were supported with a
      Hemopump as a potentially life saving measure for circulatory failure. Left
      ventricular assist time ranged from 10 to 32 h. None of the three patients could
      be successfully weaned from the device because of complications of bleeding,
      arrhythmia or neurological insult. Despite poor outcomes, each patient
      demonstrated important hemodynamic stabilization with the device. The Hemopump is
      suggested as a potentially life saving treatment modality for selected pediatric
      patients who have critical left ventricular failure.

PMID- 9179089
TI  - The role of diltiazem in treating hypertension and coronary artery disease: new
      approaches to preventing first events.
AB  - OBJECTIVE: To review the role of diltiazem in treating and preventing a group of
      cardiovascular diseases, including painful and silent cardiac ischemia, stroke,
      nonfatal myocardial infarction and sudden cardiac death, by modulating certain
      physiological causes that they appear to share. DATA SOURCES: A MEDLINE search
      was conducted for all clinical articles on the use of diltiazem for hypertension
      and coronary artery disease. When clinical data were not available, basic
      research findings were reviewed. DATA EXTRACTION AND SYNTHESIS: Because many
      cardiovascular events show a marked daily periodicity--which appears to coincide
      with circadian peaks in the ability of platelets to aggregate, sympathetic
      activity, coronary tone, blood pressure, heart rate and hematocrit, and a trough
      in fibrinolytic activity--the impact of diltizazem on these physiological changes
      was assessed. CONCLUSIONS: Diltiazem influences many of these events by
      increasing myocardial bloodflow, and reducing myocardial oxygen demand and
      cardiac workload. However, it differs from other calcium antagonists in its mild
      negative inotropic and moderate negative dromotropic effects, without apparent
      stimulation of cardiac performance or contractility. In addition, it inhibits
      platelet aggregation, decreases catecholamine release, diminishes coronary tone
      and blocks the vasoconstrictive actions of endothelin-1. This appears to
      translate into a beneficial effect on ischemia, thrombolysis, arrhythmias,
      infarct parameters, atherosclerosis and hypertension. Diltiazem has a relatively
      favourable safety and tolerability profile, and is available in a once-daily
      dosage form. The most common adverse effects are related to vasodilation (eg,
      edema and headache), and the most frequent serious adverse event is
      atrioventricular block, which occurs rarely. In summary, diltiazem appears to be
      well suited to preventing the first occurrence of cardiovascular events and may
      even have a role in preventing certain types of secondary events. The data
      accumulated so far indicate the need for a large scale random clinical trial
      addressing these outcomes.

PMID- 9179090
TI  - Evaluation of the Heart and Stroke Foundation of Canada Research Scholarship
      Program: research productivity and impact.
AB  - OBJECTIVE: To compare the research productivity, and its impact, of individuals
      awarded research scholarships from the Heart and Stroke Foundation of Canada
      (HSFC) with that of a parallel group of unsuccessful applicants during the
      funding years 1980/81 to 1989/90 inclusive. Research productivity was defined as
      the number of peer reviewed publications, and impact was evaluated from the
      number of publications cited; the number of citations per publication; the number
      of citations per individual; and the impact score. STUDY SELECTION: Data were
      collected on 192 individuals. Cohorts were defined as successful and unsuccessful
      individuals entering the system in the same year. The study comprised 10 separate
      cohorts. Data were collected on yearly publications and citation counts for each
      individual. These data, along with journal impact factors, were obtained from the
      Institute for Scientific Information. CONCLUSIONS: During the 10 years of the
      study, individuals funded by the HSFC published more papers, more of their papers
      were cited, and they received more citations per individual than the unfunded
      comparison group. This consistency in multiple indicators provides strong
      evidence that funded individuals are more productive and that their work has a
      greater impact on the body of knowledge in this area. Although this study cannot
      unequivocally show a direct causal relation between funding and research success,
      the trend as shown by the indicators studied suggests a beneficial effect.

PMID- 9179091
TI  - Exercise-induced left bundle branch block: a case report of false positive MIBI
      imaging and review of the literature.
AB  - Exercise-induced left bundle branch block is a relatively rare finding during
      exercise tolerance testing. A 36-year-old female with intermittent exercise
      induced left bundle branch block, a MIBI study suggesting anterior ischemia and
      normal coronary arteries is reported. A review of the English and French language
      literature published from January 1985 to January 1996 is presented. Exercise
      induced left bundle branch block has been reported in association with and
      without structural heart disease. Pooled mortality in the group with structural
      heart disease was 2.7% per year, and mortality was 0.17% per year when no
      structural heart disease was identified. Exercise-induced left bundle branch
      block has been reported to resolve with therapy. Noninvasive testing appears to
      have limited ability to detect or exclude coronary artery disease in this group.
      If a definitive cardiac diagnosis is required, strong consideration should be
      given to coronary angiography.

PMID- 9179092
TI  - Aortic dissection and use of the nicotine patch: a case involving a temporal
      relationship.
AB  - A 33-year-old woman presented with chest and abdominal pain shortly after first
      and second applications of the nicotine patch. Type A aortic dissection was
      diagnosed and repaired. Pathological examination revealed cystic medial necrosis,
      subacute and acute dissection, with no evidence of chronic aortic insufficiency.
      The close temporal relationship between applications of the nicotine patch and
      onset of symptoms compatible with dissection followed by extension raises the
      possibility that the nicotine patch was implicated in, or precipitated, this
      woman's aortic dissection.

PMID- 9179093
TI  - Acetylsalicylic acid and vitamin E in prevention of arterial thrombosis.
AB  - Both acetylsalicylic acid and vitamin E have been shown to be beneficial in the
      prevention of stroke and heart attacks. It is implied that their combination in
      the treatment of thrombotic complications of atherosclerosis may have added
      benefits. It is suggested that vitamin E may work as a platelet lysosome
      stabilizing agent.

PMID- 9179094
TI  - National adaptations of the ICD rules for classification--a problem in the
      evaluation of cause-of-death trends.
AB  - In 1981, the registration routines of the Swedish cause-of-death register were
      adjusted. The aim of this study was to assess what influence these changes in
      registration practice might have had on the cause-of-death trends after 1981. The
      Eighth Revision of the International Classification of Diseases (ICD-8) was used
      throughout the study period (1976-1985). Significant changes in the registered
      number of cases were found in 13 of the 18 diagnostic groups scrutinized. Four
      main types of outcomes were observed: (a) the number of underlying causes
      increased while the number of contributing causes decreased or vice versa; (b)
      the number of both underlying and contributory causes changed in the same
      direction, due to the transfer of a diagnostic group from one ICD category to
      another; (c) the number of both underlying and contributory causes changed in the
      same direction, but not due to the transfer of a diagnostic group; or (d) the
      number of either underlying or contributory causes changed, but not both. In
      general, the altered registration practice led to more conditions that are often
      considered as terminal complications to other diseases being registered as the
      underlying cause of death. While most of the 1981 instructions meant a more
      literal application of the ICD-8, those concerning cardiac valvular diseases
      deviated substantially from it. We conclude that (a) important changes in
      registration practice may occur at any point in time, and not only in connection
      with the implementation of a new version of the ICD; and (b) national adaptations
      of the ICD coding instructions may amount to a reversal of the instructions
      included in the ICD manuals. These findings must be considered when comparing
      cause-of-death statistics from different countries, and both underlying and
      contributing cause-of-death statistics should be considered in such analyses of
      cause-of-death trends.

PMID- 9179095
TI  - Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified
      Mini-Mental State Exam (3MS) compared.
AB  - The objectives of this study were to assess whether Teng's modification of the
      Mini-Mental State Examination (MMSE) improves its performance as a screening test
      for cognitive impairment and dementia, and to replicate this comparison in French
      and English language groups, and for differing assumptions concerning the
      relative importance of false negative and false positive errors. Screening
      interviews were conducted with representative samples of people aged 65 or over,
      set in 36 communities in 10 Canadian provinces. There were 8900 community
      participants in the Canadian Study of Health and Aging, of whom 1600 also
      underwent an extensive clinical and neuropsychological examination. Sensitivity,
      specificity and areas under the receiver operating characteristic (ROC) curve for
      the original MMSE and modified version (the 3MS) were the main outcome measures.
      Results are reported for French and English versions of the tests. The results
      indicate the alpha internal consistency for the 3MS was 0.87, compared to 0.78
      for the MMSE. The area under the ROC curve in identifying dementia was 0.93 for
      the 3MS and 0.89 for the MMSE (p < 0.001). There was less difference between the
      two tests in identifying all levels of cognitive impairment (AUC 0.80 versus
      0.77, p < 0.01). The superiority of the 3MS appears more due to its extended
      scoring system than to its additional questions. The validity of the MMSE was
      comparable in English and French samples; results for the 3MS were inconsistent
      between the two samples, suggesting possible translation problems. In conclusion,
      the 3MS was superior to the MMSE, justifying the slightly greater burden for its
      administration and scoring. Neither test worked well in identifying lower levels
      of cognitive impairment.

PMID- 9179096
TI  - Adherence in AIDS clinical trials: a framework for clinical research and clinical
      care.
AB  - Assessment of adherence within AIDS clinical trials is a critical component of
      the successful evaluation of therapeutic outcomes. Poor medication adherence can
      result in the misinterpretation of clinical trial data. Research on factors
      affecting adherence in AIDS clinical trials has been scarce, and few
      investigations have evaluated strategies for enhancing patient participation. One
      reason may be the absence of a conceptual framework to guide research. Consistent
      with previous research on medical adherence, we propose a framework whereby
      factors affecting adherence in AIDS clinical trials can be categorized as
      characteristics of the: (a) individual, (b) treatment regimen, (c) patient
      provider relationship, (d) clinical setting, and (e) disease. This framework is
      used as a heuristic for reviewing studies that examine factors affecting
      adherence in AIDS clinical trials. Suggestions for future research and clinical
      intervention are provided. These efforts are timely because adherence is now the
      center of attention in discourse about the efficacy of the new class of protease
      inhibitor drugs; non-adherence has been linked to viral resistance and drug
      failure. Efforts to identify factors that influence adherence to AIDS clinical
      trials can inform future attempts to improve adherence and retention. Better
      adherence protects the scientific integrity of AIDS clinical trials, promoting
      more efficient and accurate evaluations of therapeutic value. Accelerated access
      to new treatments may follow, ultimately enhancing patient care.

PMID- 9179097
TI  - Intra-individual variability of fibrinogen levels.
AB  - Elevated fibrinogen concentrations are recognized as playing an important role in
      the pathogenesis of atherosclerosis. In the framework of a risk factor survey in
      342 middle-aged working men, screened twice over a period of five months, plasma
      fibrinogen levels were found to be fairly unstable as large discrepancies between
      both measurements were observed. Due to a substantial proportion of within-person
      variability, the reliability coefficient was only R = 0.56. Repeatability was
      highest in higher educated and physically more active men. Our data suggest that
      the impact of elevated fibrinogen levels on the development of ischemic heart
      disease and stroke, is likely to be under-estimated.

PMID- 9179099
TI  - The influence of psychological and social factors on accuracy of self-reported
      blood pressure.
AB  - The data reported here document levels of accuracy in reports of blood pressure
      and identify correlates of inaccurate reporting. The data come from a long-term
      follow-up of a cohort of African-American women who registered for antepartum
      care between September, 1967 and June, 1969. At the follow-up interview, these
      women were asked whether they had ever received a diagnosis of hypertension from
      a physician. The self-reports of hypertension were compared with information
      contained in the medical records of these women. Twenty-five percent reported
      having high blood pressure but 53% of these reports were unconfirmed by their
      medical records (overall misreporting rates was 15.9% with 2.5% underreporting
      and 13.4% overreporting). The factors related to misreporting included a
      psychiatric diagnosis (based on the Diagnostic Interview Schedule) of major
      depressive disorder or drug and/or alcohol abuse and a small social network. The
      conjunction of these three variables significantly affected accuracy of reporting
      (100% misreporting with all three variables). These results suggest that, using
      currently standard methodology, there is an unreliable subpopulation of
      respondents in health surveys that may require the collection of data on health
      status from a second source to confirm data from self-reported health measures.

PMID- 9179098
TI  - Combining single patient (N-of-1) trials to estimate population treatment effects
      and to evaluate individual patient responses to treatment.
AB  - When treating individual patients, physicians may face difficulties using the
      evidence from center-based randomized control trials (RCTs) due to limitations in
      these studies generalizability. Therefore, they often perform their own
      "informal" tests of treatment effectiveness. Single patient ("N-of-1") trials
      provide a structured design for more rigorous assessment of medical treatments of
      chronic diseases, but are applied only to the index patient. We present a
      hierarchical Bayesian random effects model to combine N-of-1 studies to obtain an
      estimate of treatment effectiveness for the population and to use this population
      information to aid in the evaluation of an individual patient's trial results.
      The model's treatment effect estimates are adjustments between the population
      estimate and the individual's observed results. This adjustment is based upon the
      within-patient and between-patient heterogeneity. We demonstrate this patient
      focused method using published data from 23 N-of-1 trial results comparing
      amitriptyline and placebo for the treatment of fibromyalgia.

PMID- 9179100
TI  - A case-control evaluation of treatment efficacy: the example of magnesium sulfate
      prophylaxis against eclampsia in patients with preeclampsia.
AB  - Randomized trials are the optimal approach for evaluations of treatment efficacy
      but may not always be feasible. We study the adequacy of the case-control design
      in evaluating efficacy in a situation where the investigated therapy, namely the
      administration of magnesium sulfate for the prevention of eclampsia in patients
      with preeclampsia, has a suspected strong protective effect. A total of 66 cases
      of eclampsia were ascertained from among deliveries occurring between 1977 and
      1992 at two hospitals in Houston, Texas. Randomly selected preeclamptic controls
      were matched to cases based on hospital and month of delivery. Magnesium sulfate
      administration prior to seizure occurrence had a strong protective effect against
      eclampsia in patients with preeclampsia (OR, 0.02; 95% CI, 0.01-0.05). This
      protective effect remained when controls were stratified by the degree of
      severity of preeclampsia (mild-to-moderate OR, 0.03, 95% CI, 0.01-0.09 and severe
      OR, 0.005; 95% CI, 0.0005-0.04) and when cases were stratified by the timing of
      the first seizure (antepartum and intrapartum seizures OR, 0.01; 95% CI, 0.003
      0.05 and postpartum seizures OR, 0.03; 95% CI, 0.005-0.15). The effect also
      remained after adjustment for other important predictors in a multivariate
      logistic regression model (OR, 0.11; 95% CI, 0.03-0.38). The results of this
      study are in support of a recent randomized trial on the efficacy of magnesium
      sulfate as a prophylactic agent against eclampsia. Although there are serious
      potential sources of bias in this study, the magnitude of the protective effect
      of magnesium sulfate minimizes the likelihood that this effect can be explained
      by bias. Observational studies could be appropriate complements or alternatives
      to randomized trials in situations where a strong treatment effect is expected.

PMID- 9179101
TI  - Longitudinal trends in total serum cholesterol levels in a Japanese cohort, 1958
      1986.
AB  - The 28-year follow-up of a Japanese cohort, having collected vast amounts of data
      collected on total serum cholesterol (TC), provided an exceptional opportunity to
      examine TC temporal trends. The longitudinal statistical method of growth-curve
      analysis was used to elucidate the age-related changes in TC levels and to
      characterize these trends in relation to sex, birth cohort, time period, place of
      residence, and body mass index (BMI). Japanese TC levels at initial examination
      were remarkably lower than those in western countries. During the study period
      from 1958 to 1986, TC levels increased dramatically with age in both sexes. The
      slope of the cholesterol growth curve was steeper for women than for men, with
      the difference growing larger after age 40 years. Drastic changes in Japanese
      behavior and lifestyle, especially westernization of the diet, are thought to
      have affected the TC values as time-period effects. As a result of this temporal
      change, which affected different cohorts at different ages, TC values were higher
      in members of the younger cohort. The increase of the TC values as time-period
      effects were larger in earlier period than in later period. These time-period
      effects appeared to be almost similar in men and women. The TC growth curves also
      varied by city of residence. Subjects in urban areas had higher TC values than
      subjects in rural areas. Changes associated with BMI from 1958 to 1986 were only
      partially responsible for the increased steepness of the TC growth curve.

PMID- 9179102
TI  - Fitting a routine health-care activity into a randomized trial: an experiment
      possible without informed consent?
AB  - Due to possible methodological and practical problems, many researchers refrain
      from using a randomized controlled trial design to evaluate procedures already
      embedded in routine health care. We performed a randomized controlled trial on
      the effects of routine individual feedback on test ordering behavior of family
      physicians. The trial started after 4 years of feedback and lasted for 2.5 years.
      With some adaptations a randomized trial proved to be possible. In evaluating
      health-care procedures that cannot be blinded in a traditional way, asking full
      and study-specific informed consent may conflict with the validity of the design.
      In such studies, an alternative procedure is to be considered. Our trial, with
      doctors as study subjects, was held on an already accepted routine procedure
      (feedback). This made it possible to refrain from obtaining study-specific
      informed consent. Consequently, a Hawthorne effect and contamination of the trial
      arms through information leakage could be avoided. Justification and general
      criteria for not obtaining full and study-specific informed consent are worked
      out. In health-care research on the performance of doctors or on interventions
      into the quality of care, obtaining a general informed consent in advance is an
      acceptable alternative approach.

PMID- 9179103
TI  - Validation of the EORTC QLQ-C30 quality of life questionnaire through combined
      qualitative and quantitative assessment of patient-observer agreement.
AB  - Patient-rated questionnaires are increasingly used to assess health-related
      quality of life. We studied one aspect of the validity of such measures that has
      rarely been investigated do patients interpret questionnaires in the same way as
      do the researchers reporting the results? If not, there may be a problem. We
      employed the EORTC QLQ-C30 quality-of-life questionnaire to study 95 cancer
      patients and measured the agreement between (1) the patient's self-assessment and
      (2) an observer's rating of the patient's open-ended responses to the same
      questionnaire administered as an interview. The observer made qualitative
      recordings describing potential misinterpretations. The agreement between
      patients' and observers' ratings was high (median kappa = 0.85, range 0.49-1.00).
      The qualitative data revealed a few minor validity problems. One of these,
      selective reporting, may lead to systematic errors; some patients reported only
      what they considered "relevant" symptoms. The combination of quantitative and
      qualitative methods proved useful for questionnaire validation.

PMID- 9179104
TI  - Evaluation of the MOS SF-36 Physical Functioning Scale (PF-10): II. Comparison of
      relative precision using Likert and Rasch scoring methods.
AB  - This study examined the relative precision (RP) of two methods of scoring the 10
      item Physical Functioning Scale (PF-10) from a large sample of patients (n =
      3445) of the Medical Outcomes Study. Based on a Likert scaling model, the PF-10
      summated scoring method was compared with a Rasch Item Response Theory (IRT)
      scaling model in which raw scores were transformed into a latent trait variable
      of physical functioning. Potential differences between scoring methods were
      hypothesized to be attributed to: (1) the logarithmic nature of the Rasch
      transformation; (2) the unevenness of the PF-10 item distributions; and (3)
      reduction of within-group variance. RP ratios favored the Rasch model in
      discriminating between patients who differed in disease severity. The Rasch and
      Likert scoring models performed similarly for tests involving sensitivity to
      change over a two-year follow-up period. In all comparisons, differences between
      methods were most apparent in clinical groups whose scores most approximated the
      extremes of the score distribution. Further research is necessary to test for
      differences between scoring models in discrimination and sensitivity to change
      among clinical groups whose scores are sufficiently spread across the continuum
      of physical functioning, in particular patients with either very high or low
      physical functioning. The Rasch model of scoring may have important implications
      for the clinical interpretation of individual scores at all ranges of the scale.

PMID- 9179105
TI  - Are results of the SF-36 health survey and the Nottingham Health Profile similar?
      A comparison in COPD patients. Quality of Life in COPD Study Group.
AB  - A number of questionnaires have been used to assess the health-related quality of
      life of patients with chronic obstructive pulmonary disease (COPD). The study
      compares the performance of the SF-36 and the Nottingham Health Profile (NHP) in
      a sample of 321 male patients with COPD. Score distributions, reliability
      estimates, and several item scaling tests, including Rasch analysis were
      compared. Finally, we assessed the relative ability of the two instruments
      considered in discriminating different levels of disease severity by comparing:
      (a) their correlations with dyspnea and %FEV1; the receiver operating
      characteristic (ROC) curves; and the F-statistics. The SF-36 scores were less
      skewed and more homogeneously distributed than NHP scores. Item scaling tests and
      reliability estimates showed a better performance of SF-36 items and scales.
      Nevertheless, results of Rasch analysis evidenced that both instruments have very
      similar scaling characteristics. Validity results did not show a consistent
      pattern of superiority for either of the instruments. For the physical domain,
      correlations of NHP and SF-36 scores with %FEV1 and dyspnea were very similar and
      substantial (tau > or = 0.30). F-statistics showed that SF-36 physical scale was
      more precise (86%) than the NHP counterpart in discriminating among levels of
      dyspnea and %FEV1 impairment. Nevertheless, the ROC curve and its associated area
      under the curve did not show a significant difference (p > 0.10). Overall results
      suggest that both instruments are similar in discriminating among different
      levels of respiratory impairment.

PMID- 9179106
TI  - Does age at natural menopause affect mortality from ischemic heart disease?
AB  - We examined the relationship between age at natural menopause and mortality of
      ischemic heart disease in 19,309 Norwegian postmenopausal women. A total of 2767
      fatal infarctions occurred during 29 years of follow up. Overall, a relatively
      weak inverse relationship was seen with approximately 10% lower ischemic heart
      disease mortality in women aged > or = 47 years at the menopause compared to
      women with an early menopause (< 44 years). Risk estimates were similar for women
      aged 47 and more at menopause. However, the inverse relationship was stronger and
      statistically significant (p = 0.01) in women aged less than 70 years. In this
      group of women, we observed a nearly 60% reduction in the ischemic heart disease
      mortality in women with a late menopause (> or = 53 years) compared to women aged
      < 44 years at menopause (mortality rate ratio = 0.42; 95% confidence interval
      0.25-0.72). This protective effect of a late menopause is reduced with advancing
      age, however, and is of minor significance in the age groups where the great
      proportion of the ischemic heart disease deaths occur.

PMID- 9179107
TI  - On the determination of contraceptive prevalence using health care utilization
      data.
AB  - A potential application of health care utilization databases is in the
      determination of contraceptive prevalence. A model linking specific factors
      concerning the utilization of modern methods of family planning has been
      developed to estimate contraceptive prevalence by age group for Saskatchewan. The
      limitations of these estimations of contraceptive prevalence are discussed.

PMID- 9179108
TI  - General practitioners' drug prescribing practice and diagnoses for prescribing:
      the More & Romsdal Prescription Study.
AB  - We have examined the prescribing patterns among general practitioners (GPs) in a
      Norwegian county in relation to the patients' age and sex and the diagnosis for
      prescribing. Altogether 69,843 contacts with patients were recorded during which
      56,758 items were prescribed. The average number of items prescribed per patient
      contact was 0.81 (male 0.76, female 0.83). Diazepam, the compound analgesic of
      paracetamol (i.e. acetaminophen) and codeine, and triazolam were the three most
      frequently prescribed drugs for females as compared to phenoxymethylpenicillin,
      paracetamol/codeine and diazepam for males. Insomnia was the most frequently
      recorded diagnosis for prescribing. Listed second were upper respiratory tract
      infections (males) and anxiety (females). Hypertension was the number three
      diagnosis. The twenty most frequently prescribed items accounted for 48.5% of all
      drugs prescribed and the twenty most frequently recorded diagnoses for
      prescribing accounted for 61.7% of all diagnoses. This makes it possible to
      analyze a substantial part of the GPs' total prescribing by focusing on a few
      drugs or diagnoses.

PMID- 9179109
TI  - Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC):
      the politics and positives of a cooperative study group for the PICNIC.

PMID- 9179110
TI  - Status versus ability in function.

PMID- 9179111
TI  - Experimental, clinical, and metabolic results of side-to-side portacaval shunt
      for intractable cirrhotic ascites.
AB  - BACKGROUND: Intractable ascites, refractory to medical therapy, occurs in
      approximately 10 percent of patients with ascites from cirrhosis and is almost
      always fatal. Sinusoidal hypertension resulting from hepatic venous outflow
      obstruction plays a primary role in the pathogenesis of cirrhotic ascites and
      provides the rationale for decompression of the liver by side-to-side portacaval
      shunt in treatment of intractable ascites. This report presents the experimental
      basis for the use of side-to-side shunt and long-term results of a prospective
      study in 34 selected patients with intractable cirrhotic ascites. STUDY DESIGN:
      In the experimental studies, hepatic venous outflow obstruction and massive
      ascites were produced in dogs by ligation of the hepatic veins, and the effect of
      portacaval shunts on ascites, thoracic duct lymph flow, and aldosterone secretion
      were measured. In the clinical study, 34 carefully selected patients with
      cirrhosis (91 percent alcoholic) and truly intractable ascites (failure of
      medical therapy for 5 to 24 months) underwent side-to-side portacaval shunt. The
      effects on ascites, survival, metabolic abnormalities, and quality of life were
      studied prospectively during follow-up that was longer than 5 years in all but
      two patients. Quantitative Child's risk classes in percent of patients were A in
      0, B in 68, and C in 32. RESULTS: In the experimental studies, side-to-side
      portacaval shunt permanently relieved severe ascites, reduced the 13-fold
      increase in thoracic duct lymph flow rate to almost normal, and abolished the
      aldosterone hypersecretory response to minimal hepatic venous outflow
      obstruction. End-to-side portacaval shunt was much less effective. In the
      clinical study, side-to-side portacaval shunt reduced mean portal vein-inferior
      vena cava pressure gradient from 282 mm saline to 4 mm and permanently relieved
      all patients of ascites without subsequent requirement of diuretic therapy. Two
      patients who died of hepatoma, and one who died of heart failure developed
      terminal ascites. Thirty-day mortality rate was 6 percent, and long-term survival
      rates at 5, 10, and 15 years were 75 percent, 74 percent, and 73 percent. In
      metabolic studies, side-to-side shunt produced marked diuresis and natriuresis
      and abolished hypersecretion of aldosterone. Quality of life was generally
      improved as a result of a low incidence of recurrent portal-systemic
      encephalopathy (6 percent), abstinence from alcohol in 91 percent, improvement in
      liver function in 81 percent, and improvement in Child's risk class. The
      portacaval anastomosis remained permanently patent in every patient. CONCLUSIONS:
      Side-to-side portacaval shunt is very effective treatment of intractable ascites
      from cirrhosis. Our results are attributable to careful selection of patients, an
      organized system of care, and a program of rigorous, lifelong follow-up that
      emphasizes abstinence from alcohol and dietary protein restriction.

PMID- 9179112
TI  - Bile duct injury during laparoscopic cholecystectomy: a prospective nationwide
      series.
AB  - BACKGROUND: The risk of bile duct injury in laparoscopic cholecystectomy has been
      a concern since the procedure became part of the surgical armamentarium. Our
      study assesses the incidence, types, and treatment for laparoscopic bile duct
      injury. STUDY DESIGN: Prospective case registration in a national database with
      participation by all departments of surgery performing laparoscopic
      cholecystectomy in Denmark since the first operation in January 1991. The case
      notes for bile duct injury have been reviewed. RESULTS: From 1991 through 1994,
      57 of 7,654 patients sustained bile duct injury (0.74 percent; 95 percent
      confidence interval, 0.55 percent to 0.94 percent), including nine injuries
      occurring after conversion. The annual incidence did not decrease. Thirty-nine
      percent of the laparoscopic bile duct injuries were incisions, 39 percent were
      transections, and 12 percent were clip injuries or strictures. One patient, who
      sustained transection during open reoperation for bleeding after a converted
      procedure, died. Bile leaks for reasons other than bile duct injury occurred in
      2.1 percent; 71 percent of these were cystic duct leaks. Acute cholecystitis was
      the indication for laparoscopic cholecystectomy in 968 patients, with 1.3 percent
      sustaining laparoscopic bile duct injury (95 percent confidence interval, 0.62
      percent to 2.08 percent), while the incidence in patients with other indications
      for laparoscopic cholecystectomy was 0.62 percent (95 percent confidence
      interval, 0.44 percent to 0.82 percent) (p > 0.05). Preoperative knowledge of
      bile duct anatomy was available by means of preoperative endoscopic retrograde
      cholangiopancreatography or intravenous cholangiography in 26 percent of patients
      undergoing laparoscopic cholecystectomy but this did not reduce the risk of bile
      duct injury. The frequency of bile duct injury in patients who had intraoperative
      cholangiography was not significantly different from those who did not.
      Intraoperative cholangiography was done in 14 cases of injury (diagnostic for
      injury in 8, misinterpreted in 2, and normal in 4 patients). The case notes
      described operative difficulties in 11 of 48 cases of laparoscopic bile duct
      injury, most often because of fibrosis or difficulty delineating the anatomy.
      CONCLUSIONS: The incidence of bile duct injury in laparoscopic cholecystectomy is
      higher than previously generally anticipated and did not decrease from 1991
      through 1994. Risk factors and possible preventive measures should be evaluated
      in prospective studies.

PMID- 9179114
TI  - Lymph node metastases detected in the mesorectum distal to carcinoma of the
      rectum by the clearing method: justification of total mesorectal excision.
AB  - BACKGROUND: Total mesorectal excision effectively reduces the local recurrence
      rate of carcinoma of the rectum. This study was undertaken to clarify the
      rationale for total mesorectal excision. STUDY DESIGN: We retrospectively
      reviewed the records of 198 patients who underwent resection of a carcinoma of
      the rectum. The presence of nodal metastases in the mesorectum distal to the
      primary tumor was examined by the clearing method. RESULTS: The metastatic rate
      in the distal mesorectum was 20.2 percent. The metastatic rates according to the
      extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent;
      pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3
      percent; and lower rectum, 19.2 percent. The longest distal spread from the
      primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4
      cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum.
      CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4
      tumors in the lower rectum, and excision of all mesorectal tissue down to at
      least 5 cm below the tumor is required for patients with T3 and T4 tumors in the
      upper rectum.

PMID- 9179113
TI  - Laparoscopic pneumodissection: results in initial 20 patients.
AB  - BACKGROUND: The efficiency of laparoscopic procedures has been hindered by a lack
      of instrumentation for blunt tissue dissection. We evaluated here the efficacy of
      a new 5-mm laparoscopic dissecting instrument, a pneumodissector. This instrument
      allows the surgeon to use short bursts of high-pressure carbon dioxide to bluntly
      dissect fatty tissue. STUDY DESIGN: In 20 patients undergoing a variety of
      laparoscopic procedures, a 5-mm laparoscopic pneumodissector was used. Subjective
      assessment of the efficacy of the instrument was recorded. In addition, acid-base
      changes were measured by blood gas determination, and serum chemistries were
      obtained before, during, and after the procedure. RESULTS: The pneumodissector
      enhanced dissection of the kidney, ureter, and major blood vessels and shortened
      the operative time for laparoscopic nephrectomy. Although statistically
      significant changes in acidbase values occurred with use of the pneumodissector,
      these changes were not clinically significant and were no different than what is
      normally seen during carbon dioxide pneumoperitoneum. CONCLUSIONS: Laparoscopic
      pneumodissection is a safe and efficacious technique for rapid blunt tissue
      dissection.

PMID- 9179115
TI  - A reader's guide to surgical decision analysis.
AB  - BACKGROUND: Studies using decision analysis appear increasingly often in the
      surgical literature. Because readers and reviewers may be unfamiliar with
      decision analysis, we review the technique and provide guidance on its
      interpretation. STUDY DESIGN: Review article. RESULTS: Decision analysis is a
      systematic approach to structuring a decision, collecting relevant information
      about the probability and relative value of outcomes, and making quantitative
      recommendations. Decision analysis includes the following basic components: (1)
      the decision model, (2) the probabilities of clinical outcomes in the model, (3)
      the utilities of clinical outcomes, and (4) the analysis and interpretation. To
      critically interpret the results of a decision analysis, readers must consider
      the validity of each component. The model should include all relevant clinical
      strategies and all important clinical outcomes. Probability estimates, whether
      derived from published studies or based on "clinical consensus," should be in
      general agreement with the reader's clinical experience. Utilities (values
      assigned to outcomes) are often expressed in terms of quality-adjusted life
      expectancy. Methods used to estimate life expectancy and to adjust for quality of
      life must be scrutinized carefully. Within the analysis, readers should consider
      the effect of varying uncertain variables in the model (sensitivity analysis)
      and, thus, the stability of the results. Finally, readers must assess whether the
      magnitude of expected benefit from the favored clinical strategy is clinically
      important. CONCLUSIONS: As decision analysis becomes more frequently used to
      influence clinical policy in surgery, surgeons must learn to examine the
      technique more critically.

PMID- 9179116
TI  - Influence of parenteral progesterones on the prevalence and severity of mastalgia
      in premenopausal women: a multi-institutional cross-sectional study.
AB  - BACKGROUND: More than 30 percent of women seen in surgical breast clinics suffer
      from mastalgia. Although the causes of mastalgia are poorly understood,
      imbalances in estrogen and progesterone effects in the breast have been
      implicated. Progesterones have been proposed as a treatment for mastalgia, but
      the literature supporting their use is conflicting and currently inconclusive.
      STUDY DESIGN: The prevalence and severity of mastalgia in women receiving
      parenteral progesterones for contraception was compared to that of a randomly
      selected, age-matched control group using a validated survey instrument. Surveys
      were completed by 671 case subjects and 1,433 randomly selected, age-matched
      control subjects. RESULTS: Nine percent of women using medroxyprogesterone
      acetate (Depo-Provera, Upjohn, Kalamazoo, Mich) reported frequent breast pain
      compared to 21 percent of control subjects (OR 0.220, p < 0.001). The prevalence
      of clinically significant breast pain was 2.3 percent in the progesterone group
      compared to 4.9 percent in the control group (p < 0.02). Focal, noncyclic
      mastalgia predominated in the progesterone group with continued breast pain (78.8
      percent), while diffuse, cyclic breast pain was more common in the control group
      (67.7 percent, p < 0.001). CONCLUSIONS: Medroxyprogesterone acetate effectively
      suppresses cyclic mastalgia in reproductive-age women and warrants additional
      study as a primary therapy.

PMID- 9179117
TI  - Papillary carcinoma of the thyroid: can operative management be based solely on
      fine-needle aspiration?
AB  - BACKGROUND: Fine-needle aspiration cytology is sensitive for detecting
      malignancies such as papillary carcinoma of the thyroid gland. Because fine
      needle aspiration specificity for papillary carcinoma of the thyroid is variable,
      routine intraoperative frozen section is often advocated. STUDY DESIGN: To define
      the roles of fine-needle aspiration and frozen section in papillary carcinoma of
      the thyroid gland, we reviewed data from 82 patients who underwent thyroidectomy
      between August 1989 and August 1995 for papillary carcinoma of the thyroid
      cytology. Results of fine-needle aspirations were grouped into three categories:
      diagnostic of papillary carcinoma of the thyroid; diagnostic of follicular
      variant of papillary carcinoma of the thyroid; or suspicious for papillary
      carcinoma of the thyroid. Definitive diagnoses were made on permanent histology.
      RESULTS: A fine-needle aspiration revealing papillary carcinoma of the thyroid
      was 98 percent specific for cancer or 100 percent specific for follicular-variant
      of papillary carcinoma of the thyroid. A fine-needle aspiration that was
      suspicious for papillary carcinoma of the thyroid (n = 24) was only 54 percent
      specific for cancer. On the basis of gross intraoperative findings, 5 of these 24
      patients underwent total thyroidectomy without frozen section, and all had
      carcinoma. The other 19 had frozen section analysis. Of the 5 patients with
      cancer detected by frozen section, 4 had cancer on permanent histology. Findings
      on frozen section demonstrated a follicular neoplasm in the other 14 patients, of
      which 4 ultimately were cancer. CONCLUSIONS: When papillary carcinoma of the
      thyroid or follicular-variant of papillary carcinoma of the thyroid is
      definitively diagnosed on fine-needle aspiration, the surgeon can perform
      definitive thyroidectomy without frozen section because of the high specificity
      for cancer. If the fine-needle aspiration is suspicious for papillary carcinoma
      of the thyroid, the incidence of cancer is 54 percent, and patients with these
      conditions should undergo surgery with frozen section. When either gross findings
      or frozen sections suggest malignancy, definitive thyroidectomy can be performed
      because 90 percent of such cases will be cancer. If frozen section is not
      diagnostic of malignancy, a thyroid lobectomy/isthmusectomy is recommended
      because 71 percent have a benign lesion. This systematic approach to papillary
      carcinoma of the thyroid will obviate unnecessary frozen sections while
      maintaining excellent diagnostic specificity.

PMID- 9179118
TI  - Optimal surgical strategy for potentially curable serosa-involved gastric
      carcinoma with intraperitoneal free cancer cells.
AB  - BACKGROUND: Radical gastrectomy with systematic lymphadenectomy (RG) remains
      controversial in the treatment of gastric carcinoma. On the other hand, the
      prognosis of gastric carcinoma, in the presence of intraperitoneal free cancer
      cells, is poor. The optimal surgical strategy for serosa-involved gastric
      carcinoma with intraperitoneal free cancer cells remains undefined. STUDY DESIGN:
      A prospective study of intraperitoneal cytologic washing was conducted on 134
      patients with potentially curable serosa-involved gastric carcinoma who underwent
      RG. During the same period, 28 patients with resectable tumors who received
      palliative simple gastrectomies because of the presence of gross incurable
      conditions (eg, multiple hepatic metastases, peritoneal carcinomatosis, or extra
      abdominal metastasis) were used as controls. RESULTS: Intraperitoneal free cancer
      cells were found in 26 patients (19.4 percent). Compared with the remaining 108
      patients without free cancer cells, there were no significant differences in the
      clinicopathologic characteristics and pathologic stages. No patients died after
      palliative resection, but five patients died after RG. The patients with free
      intraperitoneal free cancer cells had a poorer long-term prognosis after RG than
      those without free cancer cells (p < 0.0001). The prognosis for such patients was
      similar to the prognosis of those who underwent palliative resection.
      CONCLUSIONS: A peritoneal washing cytologic examination is mandatory before
      resection for potentially curable serosa-involved gastric carcinoma. When free
      cancer cells appear in the washing fluid, the cancer is incurable. Simply
      gastrectomy without additional lymphadenectomy is the optimal strategy for
      treatment.

PMID- 9179119
TI  - Open heart operations without transfusion using a multimodality blood
      conservation strategy in 50 Jehovah's Witness patients: implications for a
      "bloodless" surgical technique.
AB  - BACKGROUND: Blood transfusion persists as an important risk of open heart
      operations despite the recent introduction of a variety of new pharmacologic
      agents and blood conservation techniques as independent therapies. A
      comprehensive multimodality blood conservation program was developed to minimize
      this risk. STUDY DESIGN: To provide a strategy for operating without transfusion,
      this program was prospectively applied to 50 adult patients who are Jehovah's
      Witnesses and have undergone open heart operation at our institution since 1992.
      The blood conservation program used for these patients included the use of high
      dose erythropoietin (800 U/kg load, 500 U/kg every other day), aprotinin (6
      million U total dose full Hammersmith regimen), "maximal" volume intraoperative
      autologous blood donation, intraoperative cell salvage, continuous shed blood
      reinfusion, and drawing as few blood specimens as possible. RESULTS: Procedures
      performed included first-time coronary bypass operations (n = 30) and more
      complex operations, including reoperations, valve replacements, and multiple
      valve replacements with or without coronary bypass (n = 20). Despite the absence
      of transfusion, the mean discharge hematocrit in these patients was greater than
      30 percent, and there was no anemia-related mortality rate in this group. The
      overall in-hospital mortality for the group was 4 percent. A subset analysis was
      performed between the 30 first-time coronary bypass patients (group 1) and a
      control group of 30 consecutive patients who were not Jehovah's Witnesses but had
      undergone first-time coronary bypass during the same period (group 2). The blood
      conservation program described in the previous paragraph was not used in group 2
      patients and specific transfusion criteria were prospectively applied. The chest
      tube output in group 1 patients was less than 40 percent of that for group 2
      patients at all points measured after operation (p < 0.01). Postoperative
      hematocrit levels in group 1 were greater than those for group 2, despite the
      absence of red blood cell transfusion and despite a significantly lower admission
      hematocrit and red blood cell mass in group 1. The average length of stay and
      ancillary costs for the two groups were equivalent. Although group 1 and 2
      patients were well matched for preoperative transfusion risk factors, none of the
      group 1 patients required transfusion, but 17 (57 percent) group 2 patients met
      transfusion criteria and received 3.0 +/- 4.8 U (mean plus or minus standard
      deviation) of homologous blood or blood products. CONCLUSIONS: These results
      suggest that even complex open heart operations can be performed without
      homologous transfusion by optimally applying available blood conservation
      techniques. More generalized application of these measures may increasingly allow
      "bloodless" operations in all patients.

PMID- 9179121
TI  - Protective effect of nafamostat mesilate in early wound healing.
AB  - BACKGROUND: Tensile strength in rat ileal anastomosis is diminished after
      injection with superoxide dismutase. We have studied the immunohistochemistry of
      extracellular matrix to investigate changes associated with this loss of tensile
      strength. A serine proteinase inhibitor, Nafamostat mesilate, was used to
      evaluate its potential for maintaining tensile strength. STUDY DESIGN: Four
      groups of rats underwent ileal anastomosis, Groups 1 and 2 were controls. Groups
      3 and 4 were given superoxide dismutase and Nafamostat mesilate, respectively,
      after anastomosis. RESULTS: In controls, groups 1 and 2, tensile strength
      decreased to 58 percent and 57 percent, respectively, of the initial value
      measured immediately after anastomosis 1 day postoperatively and both dropped to
      33 percent 3 days postoperatively. After 5 days, tensile strength recovered to 83
      percent of initial value. In comparison with controls, administration of
      superoxide dismutase significantly attenuated the loss of tensile strength on day
      1 (94 percent of initial value, p < 0.01) and on days 3, 5 and 7 (p < 0.05).
      Similar results were found after administration of Nafamostat mesilate on days 3
      and 5 (p < 0.05). In group 1, degradation of the collagen layer in the
      anastomosis was observed, with disappearance of immunostaining for fibronectin
      and vitronectin on day 3. In both groups 3 and 4, these changes were
      significantly attenuated with intense immunostaining for plasminogen activator
      inhibitor-1; fibronectin and vitronectin were seen particularly among collagen
      fibers on both sides of the anastomosis. CONCLUSIONS: These findings suggest that
      degradation of extracellular matrix causes loss of tensile strength early after
      anastomosis. Nafamostat mesilate may be clinically useful to prevent breakdown of
      intestinal anastomoses.

PMID- 9179120
TI  - Pyloroplasty and pyloromyotomy in gastric replacement of the esophagus after
      esophagectomy: a randomized controlled trial.
AB  - BACKGROUND: Drainage methods for the gastric conduit after esophagectomy for
      carcinoma have been controversial. STUDY DESIGN: In a randomized controlled
      trial, 92 patients with esophageal carcinoma were randomized to have pyloroplasty
      or pyloromyotomy as a drainage procedure for the gastric conduit used for
      esophageal replacement. Only patients who underwent Lewis- Tanner operation or
      esophagogastrectomy and who had normal pyloroduodenal regions were included.
      RESULTS: The mean postoperative daily nasogastric output (SEM) were 164 mL (17
      mL) in the pyloroplasty group and 179 mL (21 mL) in the pyloromyotomy group (p =
      not significant). No leakage occurred at the pyloroduodenal region in either
      group. In both groups, the anastomotic leakage rate was 2 percent, and the in
      hospital mortality rate was 7 percent. No significant difference was found in
      postoperative morbidity and mortality. Gastric outlet obstruction developed in
      only two patients who underwent pyloromyotomy, and both required reexploration.
      One died of malignant obstruction of the gastric outlet and aspiration pneumonia.
      Scintigraphy performed 6 months after operation showed that the median half-life
      (interquartile range) for gastric emptying was 19 minutes (10 to 24 minutes) in
      the pyloromyotomy group and 8 minutes (5 to 19 minutes) in the pyloromyotomy
      group (p = 0.04). Long-term follow-up up to 5 years, however, did not reveal
      significant differences between the two groups in the type and quantity of food
      consumed. The incidence of other symptoms such as regurgitation, diarrhea, bile
      reflux, and dumping, also was no different. CONCLUSIONS: Pyloroplasty and
      pyloromyotomy were effective and safe drainage procedures for the gastric conduit
      used for esophageal replacement. The choice depends on the preference and
      experience of the surgeon. Most patients adapted to their new conduit with time.

PMID- 9179122
TI  - Etiologic diagnosis of pericardial disease: the value of routine tests during
      surgical procedures.
AB  - BACKGROUND: The cause of pericardial disease often is unclear. Pericardial
      surgery provides a unique opportunity to obtain tissue and fluid samples for
      diagnostic tests. We report our experience with these tests and assess their
      value in etiologic determination. STUDY DESIGN: The medical records of 92 who
      underwent 95 operations for pericardial disease were reviewed. The procedures
      included 75 biopsies and drainages and 20 pericardiectomies. We analyzed the
      diagnostic yields of routine histology of the removed pericardial specimens,
      together with culture, cytology, and biochemistry examinations of the fluid
      drained. RESULTS: A specific etiologic diagnosis was obtained in 20 patients (22
      percent): 12 neoplasias, 5 infections (1 bacterial, 4 tuberculoses), 2
      chylopericardia, and 1 amyloidosis. Diagnosis was made histologically in 10 (10.5
      percent) of 95 examinations, cytologically in 12 (16 percent) of 73 examinations,
      by culture in 5 (7 percent) of 73 examinations, and by biochemistry in 2 (3
      percent) of 73 examinations. Pericardial disease was the first manifestation of
      an underlying extrapericardial disorder in 11 patients (12 percent), and 8 of
      these patients had neoplasias and 3 had tuberculoses. Twenty-seven patients (29
      percent) had underlying neoplastic disease, and in 15 patients, neither cytology
      nor histology revealed neoplastic involvement of the pericardium. In 2 of the 15
      patients, who died shortly after the operation, pericardial invasion was
      demonstrated at postmortem examination. CONCLUSIONS: One fifth of the patients
      had a specific etiologic diagnosis with important implications for prognosis and
      management, supporting the routine use of diagnostic tests in all pericardial
      surgical procedures. Negative cytology and histology results do not rule out
      pericardial invasion in patients with neoplastic disease.

PMID- 9179123
TI  - Portacaval shunts for ascites: another perspective.

PMID- 9179124
TI  - Jejunostomy with replaceable feeding tube: a new technique.

PMID- 9179125
TI  - Antegrade laparoscopic common bile duct stone removal using a balloon-tipped
      embolectomy catheter.

PMID- 9179126
TI  - Apoptosis: its role in the progression of and chemotherapy for carcinoma.

PMID- 9179127
TI  - Effect of lymph node dissection on survival of gastric carcinoma.

PMID- 9179129
TI  - Curative gastrectomy.

PMID- 9179128
TI  - Cholecystectomy and AIDS.

PMID- 9179130
TI  - Axillary lymph node metastasis in carcinoma of the breast.

PMID- 9179131
TI  - Dr. Charles H. Mayo's postwar activities and prediction of germ warfare.

PMID- 9179132
TI  - Tropicamide eyedrops cannot be used for reliable diagnosis of Alzheimer's
      disease.
AB  - OBJECTIVE: To evaluate the mydriatic effect of tropicamide eyedrops as a
      diagnostic test for Alzheimer's disease. MATERIAL AND METHODS: In a double-blind,
      placebo-controlled study, we assessed pupillary responses in 22 normal control
      subjects, 23 patients with probable Alzheimer's disease, 4 patients with isolated
      memory difficulty, and 6 patients with non-Alzheimer's dementia. Three separate
      studies were performed, the second and third on a subset of the original group.
      With use of infrared binocular pupillography, after 5 minutes of dark adaptation,
      we averaged pupil size during a 1-minute interval for baseline determinations. We
      then instilled 0.01% tropicamide into one eye. In the first two studies, we
      averaged pupil size for a 1-minute period at 5-minute intervals for 30 minutes,
      followed by a pupil light reflex test. In the third study, we measured pupil size
      every 5 minutes for 45 minutes and omitted the light reflex test. RESULTS: No
      significant difference was noted in pupil dilatation between normal subjects and
      patients with Alzheimer's disease and between patients with non-Alzheimer's
      dementias and the Alzheimer's disease group in all three studies. Furthermore, on
      reperformance of the test in the same patients, more than 50% changed from a
      group above or below 13% pupil dilatation (a cutoff reported to distinguish
      Alzheimer's disease from normal control subjects) to the opposite group.
      CONCLUSION: Results of this study indicate that pupil measurement after
      instillation of tropicamide cannot be used as a reliable diagnostic test for
      Alzheimer's disease. Moreover, test-retest reliability with use of dilute
      tropicamide eyedrops is questionable.

PMID- 9179133
TI  - Outcomes of patients with no laboratory assessment before anesthesia and a
      surgical procedure.
AB  - OBJECTIVE: To estimate the frequency of perioperative morbidities in patients who
      underwent anesthesia and a surgical procedure with no preoperative laboratory
      testing. MATERIAL AND METHODS: We conducted an electronic database search of
      medical records of 56,119 patients who underwent surgical or diagnostic
      procedures and anesthesia at Mayo Clinic Rochester in 1994 and found 5,120 who
      had no laboratory tests done within 90 days before the procedure. From this
      group, we randomly selected 1,044 patients (87 from each month) to document the
      absence of preoperative tests, the presence of preexisting disease (by organ
      system), the type of anesthetic agent, and the outcomes and tests
      intraoperatively and postoperatively. RESULTS: The 1,044 patients ranged in age
      from 0 to 95 years (median age, 21). No deaths or major perioperative morbidities
      occurred (0.0%; exact 95% confidence interval, 0.00 to 0.35%). Although 10
      patients underwent blood typing and screening for antibodies immediately
      preoperatively, no blood transfusions were necessary. Intraoperatively, 17
      laboratory tests and 1 electrocardiogram were obtained, and 3 results were
      abnormal. Postoperatively, 42 blood tests and 2 electrocardiographic procedures
      were performed. Five of the 42 blood tests showed abnormal results (hemoglobin
      levels in 3, serum sodium in 1, and arterial blood gases in 1). One
      electrocardiogram showed normal findings, and the other revealed normal results
      except for premature ventricular contractions. No laboratory test done
      intraoperatively or postoperatively was found to change surgical or medical
      management substantially. One patient who had unanticipated blood loss during an
      outpatient procedure was admitted to the hospital for observation. CONCLUSION:
      All 1,044 patients, 97% of whom were relatively healthy, with no recent
      laboratory testing safely underwent anesthesia and an operation. We conclude that
      patients who have been assessed by history and physical examination and
      determined to have no preoperative indication for laboratory tests can safely
      undergo anesthesia and operation with tests obtained only as indicated
      intraoperatively and post-operatively. Current anesthetic and medical practices
      rapidly identify perioperative indications for laboratory evaluation as they
      arise.

PMID- 9179134
TI  - Clinical comparison of borreliacidal-antibody test with indirect
      immunofluorescence and enzyme-linked immunosorbent assays for diagnosis of Lyme
      disease.
AB  - OBJECTIVE: To compare the clinical results with the borreliacidal-antibody test
      (BAT) and two standard screening serologic tests for Lyme disease (LD)-the
      indirect immunofluorescence assay (IFA) and the enzyme-linked immunosorbent assay
      (ELISA). DESIGN: The medical records of patients from an endemic LD area, who had
      been serologically tested during the summer of 1992, were retrospectively
      categorized by clinical diagnoses without results of serologic tests. Serologic
      testing, which included control serum samples from patients from a nonendemic LD
      area, was performed in a blinded fashion, and the results were compared with the
      clinical categories. MATERIAL AND METHODS: Medical records of 307 patients who
      had been serologically tested for LD were reviewed. We found untreated, active LD
      in 43 patients (early-localized LD, 21; early-disseminated LD, 14; and late
      disseminated LD, 8) and treated LD in 33. Non-LD cases were categorized into
      acute or chronic conditions of unknown or known cause. RESULTS: Overall, the BAT
      had a sensitivity of 11% in active LD and did not correlate with results of other
      conventional surface antibody assays. The IFA and ELISA were more sensitive (67
      to 93%), but false-positive results frequently were noted (20 to 40%) in acute
      and chronic non-LD inflammatory conditions. The specificity of the BAT, IFA, and
      ELISA in the control group was 96%, 93%, and 97%, respectively. CONCLUSION: Until
      the sensitivity, as measured by prospective clinical studies, is improved without
      loss of specificity, the BAT should not be used clinically for the diagnosis of
      LD. Suspected cases of LD with atypical clinical manifestations should have
      positive ELISA and IFA results confirmed with a standardized immunoblot assay.

PMID- 9179135
TI  - Delivery rates for preventive services in 44 midwestern clinics.
AB  - OBJECTIVE: To determine the rates at which private primary-care clinics are
      recommending blood pressure and cholesterol measurement, smoking cessation,
      clinical breast examination, screening mammography, Papanicolaou testing, and
      influenza and pneumococcus immunizations. MATERIAL AND METHODS: We conducted a
      mail survey of 7,997 randomly selected patients from 44 primary-care clinics in
      and around Minneapolis-St. Paul, Minnesota, of whom 6,830 (85.4%) completed the
      questionnaire on preventive services delivery rates. The responses were analyzed
      statistically, including stratification by reason for the clinic visit. RESULTS:
      On the average, about two-thirds of the patients in each clinic reported being up
      to-date on preventive services before their clinic visit; an exception was
      pneumococcus immunization (mean rate, 33%). Except for blood pressure and smoking
      cessation advice, less than 30% of patients who were not up-to-date on a
      preventive service were offered it if the clinic visit was for a reason other
      than a checkup or physical examination. For patients who said that they saw their
      physician for a checkup or physical examination, the rate was more than 50% only
      for Papanicolaou smear. In contrast, nearly all responding practitioners agreed
      that each of the eight preventive services was very important or important.
      CONCLUSION: Preventive services consensus goals are not being met, even for
      patients who report that their clinic visit was for a checkup or physical
      examination. This finding suggests that it may be necessary to develop clinical
      systems that support and enable the delivery of preventive services.

PMID- 9179136
TI  - Guidelines for perioperative cardiovascular evaluation for noncardiac surgery: an
      abridged version of the report of the American College of Cardiology/American
      Heart Association Task Force on Practice Guidelines.

PMID- 9179137
TI  - Infective endocarditis due to unusual or fastidious microorganisms.
AB  - Infective endocarditis due to fastidious microorganisms is commonly encountered
      in clinical practice. Some organisms such as fungi account for up to 15% of cases
      of prosthetic valve infective endocarditis, whereas organisms of the HACEK group
      (Haemophilus parainfluenzae, H. aphrophilus, and H. paraphrophilus,
      Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella
      corrodens, and Kingella kingae) cause 3% of community-acquired cases of infective
      endocarditis. Special techniques are necessary to identify these microorganisms.
      A history of contact with mammals or birds may suggest infection caused by
      Coxiella burnetii (Q fever), Brucella species, or Chlamydia psittaci. A
      nosocomial cluster of postsurgical infective endocarditis may be caused by
      Legionella species or Mycobacterium species. If risk factors that are commonly
      associated with fungal infections (cardiac surgical treatment, prolonged
      hospitalization, indwelling central venous catheters, and long-term antibiotic
      use) are present, fungal endocarditis is possible. Patients with endocarditis and
      a history of periodontal disease or dental work in whom routine blood cultures
      are negative might have infection due to nutritionally variant streptococci or
      bacteria of the HACEK group. Communication between the microbiologist and the
      clinician is of crucial importance for identification of these microorganisms
      early during the course of the infection before complications such as
      embolization or valvular failure occur. In this article, we review the
      microbiologic and clinical features of these organisms and provide
      recommendations for diagnosis and treatment.

PMID- 9179138
TI  - Trigeminal trophic syndrome.
AB  - Seven cases of trigeminal trophic syndrome are reported. In this rare condition,
      neurotrophic ulcers occur on the face, especially in the ala nasi area in a
      dermatome of the trigeminal nerve that has been rendered anesthetic, usually as a
      complication of trigeminal ablation by surgical means or injection for treatment
      of trigeminal neuralgia. The period from time of trigeminal nerve injury to onset
      of the ulcer varies from weeks to several years, with a mean of 1 to 2 years.
      Self-induced trauma is believed to produce the tissue destruction. Once the
      ulcers appear, they are extremely persistent.

PMID- 9179139
TI  - Malabsorption syndrome associated with ulceration of the stomach and small bowel
      caused by chronic intestinal ischemia in a patient with hyperhomocysteinemia.
AB  - We describe a 39-year-old woman with an 8-month history of abdominal pain,
      diarrhea, and weight loss. Clinical and laboratory evaluation indicated the
      presence of a malabsorption syndrome. Endoscopy revealed multiple gastric
      ulcerations and an abnormal "picture" of the duodenal mucosa. At duodenal biopsy,
      necrosis confined to the distal parts of the enteric villi and a
      polymorphonuclear leukocyte response were found. Further evaluation revealed
      intestinal ischemia as a result of mesenteric atherosclerosis. After a
      revascularization procedure was performed, the symptoms disappeared. The
      macroscopic and microscopic picture of the bowel normalized. In our search for
      risk factors of atherosclerosis, we found a substantially increased basal plasma
      homocysteine concentration. This case suggests that hyperhomocysteinemia may have
      a causal role in the development of symptomatic, premature atherosclerosis of the
      mesenteric circulation.

PMID- 9179140
TI  - Surgical treatment of obesity: who is an appropriate candidate?
AB  - The increasing prevalence and far-reaching medical, social, and economical
      implications of obesity have made it a national health-care crisis in the United
      States. About one in every three persons is at least 20% above "ideal" body
      weight, and approximately 5% have direct weight-related serious health problems
      (morbid obesity), including hypertension, hyperlipidemia, coronary artery
      disease, adult-onset diabetes mellitus, degenerative osteoarthropathy, and
      obstructive sleep apnea. Morbidly obese patients have an estimated 6- to 12-fold
      increase in mortality. In addition, they have a substantially diminished quality
      of life, not only physically but also psychosocially due to overt and occult
      prejudice. Weight reduction must be aggressively pursued in these patients.
      Medically supervised weight-control programs have been ineffective because
      patients cannot maintain pronounced long-term weight loss. In contrast, current
      operative methods have been proved to be effective in helping patients achieve
      and maintain permanent weight reduction. Several operations have been designed
      and assessed; with these procedures, weight loss is achieved by inducing
      malabsorption, maldigestion, early satiety, or a combination of these outcomes.
      Although these operations have associated side effects and limitations, the
      expected benefits outweigh the risks. For optimal results, patients must be
      carefully selected and treated by a multidisciplinary group.

PMID- 9179141
TI  - The melanoma epidemic: more apparent than real?
AB  - To examine inconsistencies between the growth in incidence of melanoma and more
      modest changes in melanoma-related mortality, we reviewed the medical literature
      on the incidence of melanoma diagnosis and associated mortality and on the
      changes in diagnosis and mortality over time. Increases in melanoma surveillance
      activity have been associated with increases in the diagnosis of thin melanomas,
      but the incidence of advanced tumors has changed minimally. The large increases
      in diagnosis of melanoma without commensurate increases in advanced tumors and
      mortality are not compatible with presumed malignant behavior of thin melanomas.
      Increased intensity of melanoma surveillance may artificially increase the
      incidence of melanoma by harvesting histologically "malignant" but biologically
      benign tumors. Little available evidence suggests the presence of an actual
      increase in the frequency of biologically malignant tumors. Attempts to increase
      screening intensity for melanoma may result in further increases in diagnosis of
      melanomas. Nevertheless, limitations in histopathologic diagnostic techniques
      will continue to hinder efforts at early identification of those at risk for
      death from melanoma without diagnosing melanoma in large numbers of patients with
      biologically benign pigmented skin tumors.

PMID- 9179142
TI  - Malignant melanoma: Mayo Clinic experience.
AB  - To present the Mayo Clinic experience with treatment of melanoma of the trunk and
      extremities, we reviewed previous Mayo Clinic studies on the management of
      malignant melanoma and summarized the survival data and treatment-related
      outcome. A prospective trial involving elective lymph node dissection in 171
      patients with malignant melanoma showed no advantage in overall survival and
      disease-free survival in the group whose nodes were removed. In an assessment of
      the treatment variables, a Cox stepwise multiple regression analysis showed a
      strong correlation of lesion thickness and level of invasion with survival.
      Another study of 535 patients with melanomas that involved the trunk and
      extremities, who were treated at the Mayo Clinic between 1971 and 1980, showed an
      overall survival of 83%. Patients with thin lesions (less than 0.76 mm thick) had
      a 98% 5-year survival, whereas patients with lesions 4 mm thick or thicker had
      only a 45% 5-year survival. Because the Mayo Clinic prospective randomized study
      showed no benefit for patients with melanoma who undergo immediate or delayed
      lymphadenectomy in the trunk and extremities, we do not perform elective lymph
      node dissection; however, close follow-up of patients is instituted, and lymph
      node dissection is performed when nodal involvement is first suspected.

PMID- 9179143
TI  - Malignant melanoma: an emerging and preventable medical catastrophe.
AB  - The natural history of malignant melanoma, including the diagnosis, prognosis,
      and treatment options, is reviewed in an attempt to formulate appropriate
      management strategies. Awareness on the part of clinicians is important, inasmuch
      as early detection of malignant melanoma offers the best chance for improved
      survival. Most lesions are excised with a margin of 1 to 3 cm, and follow-up
      assessment intervals are based on the depth of the primary lesion. Follow-up
      usually consists of a medical history, physical examination, chest
      roentgenography, and hematologic and chemistry profiles. Routine use of
      sophisticated imaging studies is unnecessary because the yield from such an
      approach has been low. Patients with melanomas thicker than 1.6 mm and those with
      histologic evidence of involvement of regional lymph nodes are at risk for
      development of disseminated disease and may be candidates for adjuvant therapy.
      In patients with severe weight loss and poor nutrition because of advanced
      disease, analgesic agents, stool softeners, and appetite enhancers are palliative
      measures that should be considered.

PMID- 9179144
TI  - 74-year-old woman with cough and proptosis.

PMID- 9179145
TI  - Mitomycin C chromosome stress test to identify hypersensitivity to bifunctional
      alkylating agents in patients with Fanconi anemia or aplastic anemia.

PMID- 9179146
TI  - The eyes don't have it in Alzheimer's disease.

PMID- 9179147
TI  - Perioperative assessment of patients undergoing noncardiac surgery.

PMID- 9179148
TI  - Edward M. Purcell--Nobel Prize for magnetic resonance imaging.

PMID- 9179149
TI  - Facts, fallacies, and fancies of nerve conduction studies: twenty-first annual
      Edward H. Lambert Lecture.
AB  - Optimal application of the nerve conduction study depends on an understanding of
      the principles and a recognition of the pitfalls of the technique. The
      conventional methods deal primarily with distal nerve segments in an extremity.
      Other techniques allow one to assess nerve segments in less accessible anatomical
      regions, to improve the accuracy in precisely localizing a focal lesion, and to
      increase sensitivity in detecting subclinical abnormalities. Despite certain
      limitations, these methods can provide diagnostically pertinent information if
      they are used judiciously in appropriate clinical contexts. I wish to review the
      fundamental concepts of nerve stimulation techniques and their proper
      applications in the clinical domain. The discussion primarily relates to the
      importance of reproducibility of various measures and pitfalls in the evaluation
      of conduction block.

PMID- 9179150
TI  - Contractile properties of human thenar muscles paralyzed by spinal cord injury.
AB  - The electrical and mechanical properties of paralyzed human thenar muscles were
      measured in response to supramaximal stimulation of the median nerve in
      individuals with chronic cervical spinal cord injury. These data were compared to
      those recorded from control muscles. Spontaneous motor unit activity was common
      in paralyzed muscles. There was significantly more variance in the twitch and
      tetanic forces, twitch/tetanus force ratios, twitch and tetanic half-relaxation
      times, and the stimulus frequencies which generated half-maximal force in
      paralyzed versus control muscles. Approximately half the paralyzed thenar muscles
      were significantly weaker than control muscles and their compound action
      potential amplitudes were reduced significantly. Paralyzed muscles had
      significantly higher twitch/tetanus force ratios. The mean stimulus frequency
      which generated half-maximal force was also reduced significantly. Thus for
      rehabilitation purposes, lower stimulation rates are required to elicit any given
      submaximal force from chronically paralyzed thenar muscles.

PMID- 9179151
TI  - Detection of antibody classes and subpopulations in myasthenia gravis patients
      using a new nonradioactive enzyme immunoassay.
AB  - To investigate the presence of antibodies in myasthenia gravis (MG) patients, we
      have developed a new reproducible and sensitive enzyme immunoassay (EIA-AChR), in
      which a beta subunit-specific monoclonal antibody (mAb 73) immobilizes fetal calf
      acetylcholine receptors (AChRs). We tested 92 MG patients (42 with positive and
      50 with negative antibody titers), 60 healthy controls, and 40 controls with
      other autoimmune diseases. EIA-AChR detected immunoglobulin G (IgG) titers in all
      of the seropositive samples, with a significant correlation between these and
      those obtained using the traditional immunoprecipitation method. Moreover, 5
      seronegative patients at immunoprecipitation assay were positive at EIA-AChR. EIA
      AChR was also useful in revealing: (1) a seropositive patient subpopulation with
      generalized MG who had Abs directed against alpha-Bungarotoxin binding sites; and
      (2) patients with IgM directed against fetal calf AChR (detected in 13
      seronegative and 16 seropositive MG patients, and in 6 of the patients with other
      autoimmune diseases).

PMID- 9179152
TI  - Autonomic evaluation by means of standard tests and power spectral analysis in
      multiple sclerosis.
AB  - Standard autonomic tests [heart rate response to deep breathing (HRDB), change in
      systolic blood pressure due to tilt], and spectral analysis of heart rate (HR),
      arterial blood pressure (ABP), and the associated transfer function analysis
      (gains and phases) were performed in 20 patients with multiple sclerosis to
      determine their diagnostic value. Transfer function analysis suggested impairment
      of baroreflex function in 7 patients and an alteration of cardiorespiratory
      coupling on a brain stem level in 4 patients. In addition, sympathetic vasomotor
      outflow was reduced in 2 patients (spectral ABP measures in the mid frequency
      band) and a decrease of vagal outflow was suggested by abnormal respiratory HR
      parameters in another 2 patients. An abnormal HRDB was present in 5 patients and
      was probably due to a central alteration (cardiorespiratory coupling) in 2
      patients and due to diminished respiratory effort in 1 patient. Spectral analysis
      of both HR and ABP oscillations and their transfer function may considerably
      improve the pathophysiological interpretation of cardiovascular autonomic
      dysfunction in patients with central nervous system disease.

PMID- 9179153
TI  - The role of leukemia inhibitory factor in skeletal muscle regeneration.
AB  - Although a number of cytokines have been implicated in tissue regeneration, it is
      unknown which ones actually function in vivo. Here, we use mice with a targeted
      mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF
      in muscle regeneration. Using a muscle crush model, we show that muscle
      regeneration in LIF knockout mice is significantly, reduced compared to control
      littermates. Further, targeted infusion of LIF in both normal and LIF knockout
      animals stimulated muscle regeneration, but the stimulation observed was much
      greater in the mutant animals than in controls. In contrast, interleukin-6 and
      transforming growth factor-alpha, which also stimulate myoblast proliferation in
      vitro, had no effect on regeneration. These findings demonstrate directly that
      LIF is involved in regeneration of injured muscle and points to the use of LIF as
      a therapeutic agent in the treatment of neuromuscular disease.

PMID- 9179154
TI  - Magnetic nerve root stimulation in two types of brachial plexus injury: segmental
      demyelination and axonal degeneration.
AB  - Magnetic cervical nerve root stimulation was performed in 9 patients with
      plexopathies secondary to suspension (SP) and in 12 cases with neurogenic
      thoracic outlet syndrome (NTOS). The findings were compared with those of the
      previously reported case groups: n-hexane polyneuropathy (HPNP), inflammatory
      demyelinating polyneuropathy (IDP), and motor neuron disease (MND). Muscle
      responses elicited by magnetic stimulation had very high rates of amplitude and
      area loss in the neck-axilla segments of the 6 SP patients. This, along with the
      other electrophysiological findings, suggested the presence of segmentally
      demyelinating plexus lesions. In NTOS patients, magnetic stimulation findings
      were not significantly different from those of the controls. Neck-axilla segment
      amplitude and are reduction rates in SP and IDP patients were significantly
      higher than those found in NTOS, HPNP, and MND groups, implying that magnetic
      nerve root stimulation may have a role in the demonstration of segmentally
      demyelinating lesions involving proximal nerve segments.

PMID- 9179155
TI  - Mitochondrial dysfunction with myoclonus epilepsy and ragged-red fibers point
      mutation in nerve, muscle, and adipose tissue of a patient with multiple
      symmetric lipomatosis.
AB  - We report a 64-year-old man presenting with multiple symmetric lipomatosis (MSL)
      and mitochondrial encephalomyoneuropathy. The diagnosis of a mitochondrial
      cytopathy was based on the typical clinical symptoms and signs, including chronic
      progressive external ophthalmoplegia, hearing impairment, cerebellar ataxia,
      proximal myopathy, and polyneuropathy, and on molecular genetic and histological
      examinations. As a unique finding, the A-->G(8344) myoclonus epilepsy and ragged
      red fibers point mutation was found in peripheral nerve, muscle, and adipose
      tissue. Muscle biopsy revealed multiple ragged-red fibers and other morphological
      signs of a mitochondrial myopathy. Sural nerve biopsy demonstrated a mixed axonal
      and demyelinating neuropathy with extensive loss of myelinated fibers and
      conspicuous onion bulb formations, as well as structural mitochondrial
      abnormalities on electron microscopy. These findings clearly demonstrate
      mitochondrial dysfunction in muscle, adipose tissue, and for the first time also
      in nervous tissue of an MSL patient, and strongly support the concept of
      mitochondrial cytopathy as one of the possible causes of multiple symmetric
      lipomatosis.

PMID- 9179156
TI  - Binding of antibodies against GM1 and GD1b in human peripheral nerve.
AB  - Human dorsal root ganglia (DRG), and ventral and dorsal roots were immunostained
      with rabbit antibodies recognizing GM1, GD1b, or both. Sera from rabbits
      immunized with GM1 or GD1b were separated in affinity columns into three
      fractions: Rab1, Rab2, and Rab3. Rab1 recognized only GM1, and Rab2 only GD1b;
      whereas Rab3 recognized both GM1 and GD1b, presumably by binding to the terminal
      galactosyl beta 1-3N-acetylgalactosaminyl residue. Rab2 and Rab3 immunostained
      most of the nerve cell bodies in the DRG and paranodal myelin of the ventral and
      dorsal roots, whereas Rab1 produced no significant immunostaining. These results
      show that GD1b is localized on the DRG neurons and the paranodal myelin of human
      peripheral nerve. These places may be the binding sites for anti-GD1b antibodies,
      including those cross-reactive with GM1, in the sera from patients with
      autoimmune neuropathies. GM1 may be dispersed in human DRG and dorsal and ventral
      roots.

PMID- 9179157
TI  - Fulminant Guillain-Barre syndrome with universal inexcitability of peripheral
      nerves: a clinicopathological study.
AB  - The pathological basis of nerve inexcitability in Guillain-Barre syndrome has not
      been established with certainty. We report the clinicopathological findings in a
      67-year-old patient with fulminant Guillain-Barre syndrome who died 18 days after
      onset. Three serial electrophysiological studies revealed nerve inexcitability.
      Antibodies to Campylobacter jejuni were present but there was no antiganglioside
      reactivity. Spinal root sections revealed extensive and almost pure macrophage
      associated demyelination with occasional presence of T lymphocytes and neutrophil
      leukocytes. Conversely, in femoral, median, and sural nerves the outstanding
      lesion was axonal degeneration, with some denuded axons remaining. Unmyelinated
      fibers, posterior root ganglia, and dorsal columns were preserved. Endoneurial
      postcapillary venules showed plump endothelial cells with loss of their tight
      junctions. We conclude that both primary demyelination and axonal degeneration
      secondary to inflammation account for nerve inexcitability. Our findings lend
      support to the hypothesis of increased endoneurial pressure as the cause of
      wallerian degeneration in nerve trunks.

PMID- 9179158
TI  - The effect of duration of muscle denervation on functional recovery in the rat
      model.
AB  - The effect of long-term denervation on neuromuscular recovery was studied in a
      rat hind limb model. The posterior tibial nerve was transected and repaired
      immediately or after denervation periods of 2 weeks, or 1, 3, 6, 9, or 12 months.
      Six months following reconstruction excellent axonal regeneration was seen across
      all nerve repairs irrespective of periods of denervation. However, there was a
      precipitous and profound decrease in the recovery of both muscle mass and
      integrated motor function if the reconstruction was delayed for longer than 1
      month. Rather than a progressive change proportional to the length of the
      denervation period, significant, more discrete changes occurred sometime after 1
      month of denervation that precluded a full recovery of muscle mass. Integrated
      motor function quantified using walking track analysis was impaired even after
      immediate nerve repair.

PMID- 9179159
TI  - Motor unit recruitment and discharge behavior in movements and isometric
      contractions.
AB  - The purpose of this study was to contrast the discharge patterns of the same
      motor units during movements and during isometric contractions that were produced
      with comparable torque-time characteristics. Subjects performed elbow flexion and
      extension movements with predetermined acceleration characteristics. The average
      acceleration and deceleration profiles for the movements were reproduced in the
      isometric setting by presenting the kinematic profiles as templates for torque
      production. Trained subjects were able to match the first agonist (AG1) and
      antagonist (ANT) electromyographic (EMG) bursts, but tended to produce a smaller
      second agonist burst (AG2) in the isometric contraction. Twenty-five motor units
      from triceps brachii were studied. The same motor units (with one exception) were
      recruited and subsequently discharged in a similar fashion in both the isometric
      and movement tasks in the AG1 and ANT EMG bursts, with fewer motor unit
      discharges in the AG2 burst in the isometric contraction. The central control
      mechanisms appear to be the same for the acceleration phase of movement and
      isometric contraction, but differ during the deceleration phase.

PMID- 9179160
TI  - Peptides and neuromas: calcitonin gene-related peptide, substance P, and mast
      cells in a mechanosensitive human sural neuroma.
AB  - We examined and compared a mechanosensitive human sural neuroma and a
      contralateral sural nerve collected simultaneously from a patient involved in a
      diabetic neuropathy research protocol. Using indirect immunofluorescence
      staining. we identified a striking difference in the content within axons of two
      neuropeptides, substance P (SP) and calcitonin, gene-related peptide (CGRP),
      between the contralateral nerve and the neuroma. Unlike the contralateral nerve,
      where immunofluorescence was sparse, a significant number of disorganized axon
      profiles that stained brightly positive for CGRP or SP were identified in the
      neuroma. In contrast, staining for tyrosine hydroxylase, a label of sympathetic
      axons, was largely absent except around one large arteriole. The neuroma specimen
      also contained large numbers of serotonin-containing mast cells, only noted
      occasionally in the contralateral nerve. The peptide staining and mast cell
      accumulation in the human neuroma closely resembled changes we have previously
      observed in an animal neuroma model. Local neuropeptides may play a role in the
      injury response of peripheral nerve, and may be related to mechanosensitivity.

PMID- 9179161
TI  - Moving toes and myoclonus associated with hereditary neuropathy with liability to
      pressure palsy (HNPP).
AB  - A 22-year-old male awoke with right foot drop and numbness. Nerve conduction
      studies, sural nerve biopsy, and molecular genetic analysis were consistent with
      hereditary neuropathy with liability to pressure palsy (HNPP). Two months later
      he developed involuntary flexion/extension movements of the right toes with
      associated intermittent dystonic flexion of the right foot. Over the next 2
      months these movements spread to the left foot and hand and myoclonus of the left
      trapezius and rhomboid appeared. This is the first case report of moving toes
      syndrome and segmental myoclonus in association with HNPP. The temporal and
      topographic patterns of spread of the abnormal movements suggest a central
      mechanism probably induced by peripheral pathology.

PMID- 9179162
TI  - Cutaneous silent period in syringomyelia.

PMID- 9179163
TI  - Recognition of the Martin-Gruber anastomosis.

PMID- 9179164
TI  - Selective ipsilateral neuromuscular involvement in a case of facial and somatic
      hemiatrophy.

PMID- 9179165
TI  - Nemaline rod and central core disease: a coexisting Z-band myopathy.

PMID- 9179166
TI  - Neuromuscular compartments in the long head of triceps: a morphological study in
      rabbits.

PMID- 9179167
TI  - Phrenic nerve palsies and persistent respiratory acidosis in a patient with
      diabetes mellitus.

PMID- 9179168
TI  - Intraoperative electrodiagnostic testing during cross-chest C7 nerve root
      transfer.

PMID- 9179169
TI  - Extensor digitorum brevis innervated by the tibial nerve ("all tibial foot"):
      anomalous innervation or technical pitfall?

PMID- 9179170
TI  - All ulnar motor hand without forearm communication.

PMID- 9179171
TI  - Marinesco-Sjogren syndrome: can the diagnosis be made prior to cataract
      formation?

PMID- 9179172
TI  - Whitewater rafting lessons for nursing research in turbulent times.

PMID- 9179173
TI  - Test of the health promotion model as a causal model of construction workers' use
      of hearing protection.
AB  - The health promotion model (HPM) was tested as a causal model of construction
      workers' use of hearing protection (N = 359). Theoretical and exploratory models
      fit well, with the theoretical model accounting for 36.3% of variance and the
      exploratory model accounting for 50.6% of variance in hearing protection use.
      Value of use (benefits of using hearing protection), barriers to use, and self
      efficacy were significant predictors in both the theoretical and exploratory
      models, but perceived health status was a predictor only in the theoretical
      model. In the exploratory model, where modifying factors were allowed direct
      relationships with use of hearing protection, two modifying factors--noise
      exposure and interpersonal influences-modeling--were significant predictors.
      Results of this test of the HPM are consistent with the revised HPM (Pender,
      1996). There were significant direct paths from modifying factors to behaviour.
      Use of hearing protection was best predicted by behavior-specific predictors,
      such as perceived barriers to use of hearing protection. Results support the use
      of the HPM to predict use of hearing protection.

PMID- 9179174
TI  - Effects of exercise on fatigue, aerobic fitness, and disease activity measures in
      persons with rheumatoid arthritis.
AB  - The effects of 12 weeks of low-impact aerobic exercise on fatigue, aerobic
      fitness, and disease activity were examined in a quasi-experimental time series
      study of 25 adults with rheumatoid arthritis (RA). Measures were obtained
      preintervention, midtreatment (after 6 weeks of exercise), end of treatment
      (after 12 weeks of exercise), and at a 15-week follow-up. ANOVAS for repeated
      measures showed that those subjects who participated more frequently reported
      decreased fatigue, while those who participated less frequently reported an
      increase in fatigue. All subjects, on average, showed increased aerobic fitness
      and increased right and left hand grip strength, decreased pain, and decreased
      walk time. There were no significant increases in joint count or sedimentation
      rate. Significant improvements in measures at the 15-week follow-up also were
      found. Findings indicate that persons with RA who participate in appropriate
      exercises may lessen fatigue levels and experience other positive effects without
      worsening their arthritis.

PMID- 9179175
TI  - Family strengths, motivation, and resources as predictors of health promotion
      behavior in single-parent and two-parent families.
AB  - The extent to which selected aspects of family health potential (strengths,
      motivation, and resources) predicted health work (health-related problem-solving
      and goal attainment behaviors) was examined in a Canadian sample of 138 female
      headed single-parent families and two-parent families. The mother and one child
      (age 10-14) each completed mailed self-report instruments to assess the
      independent variables of family cohesion, family pride, mother's non-traditional
      sex role orientation, general self-efficacy, internal health locus of control,
      network support, community support, and family income, as well as the dependent
      variable, health work. With the effects of mothers' education held constant, the
      independent variables predicted 22 to 27% of the variance in health work in the
      total sample and each family type. Family cohesion was the most consistent
      predictor of health work, accounting for 8 to 13% of the variance. The findings
      challenge existing problem-oriented views of single-parent families by focusing
      on their potential to engage in health promotion behavior.

PMID- 9179176
TI  - Personalizing choices: patients' experiences with making treatment decisions.
AB  - Because little is known about the perceptions of patients who make health care
      decisions under potentially life-threatening conditions, a grounded theory
      approach was utilized to describe decision making from the patient's perspective.
      Eighteen respondents, aged 26 to 81, with diagnoses of heart disease, renal
      failure, or cancer were interviewed shortly after making a decision regarding
      treatment of their conditions and again about 1 month later. Respondents reported
      that their decisions to accept treatment were personalized to correspond with
      their views of themselves within the context of their life stories. Findings
      provide a basis for development of effective interaction and educational
      strategies for use with persons with potentially life-threatening conditions.

PMID- 9179177
TI  - The utility of locus of control for predicting adolescent substance use.
AB  - Structural equation modelling (SEM) was used to examine the utility of locus of
      control (LOC) for predicting adolescent substance use. As part of a larger three
      wave cohort-sequential study (1983-1989), 155 secondary school-based adolescents
      completed questionnaires on substance use, personality characteristics,
      family/peer influences, and health behaviors. Latent variable indicators were
      developed from the Nowicki-Strickland Personal Reaction Survey and substance use
      survey items. LOC was a weak predictor of substance use. In two instances were
      relationships significant: (a) 7th grade LOC predicted 11th grade alcohol use;
      and, (b) 9th grade LOC correlated with 11th grade cannabis use. Small samples
      precluded analysis of gender and social class effects. SEM with panel data offers
      a methodological approach for examining the explanatory capability of LOC.

PMID- 9179178
TI  - Sleep, psychological distress, and stress arousal in women with fibromyalgia.
AB  - The purpose of this investigation was to compare self-reported sleep quality and
      psychological distress, as well as somnographic sleep and physiological stress
      arousal, in women recruited from the community with self-reported medically
      diagnosed fibromyalgia (FM) to women without somatic symptoms. Eleven midlife
      women with FM, when compared to 11 asymptomatic women, reported poorer sleep
      quality and higher SCL-90 psychological distress scores. Women with FM also had
      more early night transitional sleep (stage 1) (p < 0.01), more sleep stage
      changes (p < 0.03) and a higher sleep fragmentation index (p < 0.03), but did not
      differ in alpha-EEG-NREM activity (a marker believed to accompany FM). No
      physiological stress arousal differences were evident. Less stable sleep in the
      early night supports a postulate that nighttime hormone (e.g., growth hormone)
      disturbance is an etiologic factor but, contrary to several literature
      assertions, alpha-EEG-NREM activity sleep does not appear to be a specific marker
      of FM. Further study of mechanisms is needed to guide treatment options.

PMID- 9179179
TI  - Effects of 72 hours sleep deprivation on wound healing in the rat.
AB  - The purpose of this study was to examine effects of sleep deprivation on cellular
      and biochemical markers of wound healing. Expanded polytetrafluoroethylene tubing
      inserted in subcutaneous tissue created miniature wounds in the dorsal skin of 12
      rats. Seven days later, 6 rats were deprived of sleep by the platform method for
      72 hr; control rats remained on usual sleep/wake routines. Numbers of
      macrophages, granulocytes, fibroblasts, and extent of connective tissue present
      and total amounts of protein, DNA, and hydroxyproline in the implants were not
      different between sleep-deprived and control rats. There is no evidence from this
      study that sleep deprivation impairs cellular and biochemical indicators of
      tissue repair.

PMID- 9179180
TI  - Selection and use of content experts for instrument development.
AB  - Content experts frequently are used in the judgment-quantification stage of
      content validation of instruments. However, errors in instrumentation may arise
      when important steps in selecting and using these experts are not carefully
      planned. The systematic process of choosing, orienting, and using content experts
      in the judgment-qualification stage of instrument development is addressed, with
      particular attention to the often neglected, important step of familiarizing
      these experts with the conceptual underpinnings and measurement model of the
      instrument. An example using experts to validate content for a measure of
      caregiver burden is used to illustrate this stage of instrument review.

PMID- 9179181
TI  - Natural course of localized prostate cancer. a personal view with a review of
      published papers.
AB  - The course of untreated localized prostate cancer after 10 years of follow-up is
      at large unknown. As curative treatment is usually only offered patients with a
      life expectancy exceeding 10 Years, the expected course of the disease if left
      untreated is of the utmost interest. This paper aims to describe the outcome for
      patients who survive for more than 10 years when treated without curative intent.
      The results indicate that cancer specific mortality in patients with localized
      prostate cancer increases steadily over time and is approximately 50% after 15
      years. This is a much higher figure than in reported series on radical
      prostatectomy. Even if many deaths occur at an old age, prostate cancer death is
      shown to be associated with a significant morbidity, need for palliative
      treatment, hospital care and cost. Preventing prostate cancer death is therefore
      not only a matter of saving year of life but also to prevent suffering caused by
      the disease. Modern diagnostic tools, such as prostate specific antigen, seem to
      detect clinically significant cancers in the vast majority of patients. Over
      diagnosis seems to be uncommon if diagnostic procedures are restricted to
      patients with a long life expectancy. Localized prostate cancer is a slow-growing
      but progressive neoplastic disease. When diagnosed in a man with a longer life
      expectancy it should be handled as such.

PMID- 9179182
TI  - Clinical strategies for improving the radiotherapeutic management of prostate
      cancer.
AB  - The goal of treatment of localized and locally advanced prostate cancer is to
      cure without causing unacceptable complications. The recognition that cure rates
      for localized and locally advanced prostate cancer treated with traditional means
      are far lower than previously estimated (1-4) has provided the impetus to seek
      improved local therapies. In particular, 3D conformal radiation therapy (3D-CRT)
      and the combination of radiation and hormone therapy are promising. Advances in
      these and other areas are discussed below.

PMID- 9179183
TI  - In vivo proton MR spectroscopy reveals altered metabolite content in malignant
      prostate tissue.
AB  - BACKGROUND: Recently the potential of magnetic resonance (MR) methods for non
      invasive diagnosis and therapy evaluation of prostate cancer has improved
      substantially. In this study proton MR spectroscopy (1H MRS) was explored for the
      detection of cancer in the prostate. PATIENTS AND METHODS: Employing an
      endorectal probe localized 1H MRS and contrast enhanced MR imaging was performed
      on the prostate of healthy volunteers and of patients with benign prostatic
      hyperplasia (BPH) and/or prostate cancer (PCa). RESULTS: 1H MR spectra of the
      human prostate showed major signals for citrate, creatine and choline compounds.
      For cancer tissue the average citrate/choline signal ratio was significantly
      lower than for BPH and non-cancerous peripheral and central zone tissue, but
      individual ratios overlapped with ratios for normal central zone and BPH tissue.
      Low citrate/choline ratios in tumour tissue correspond with early MR contrast
      enhancement. CONCLUSIONS: 1H MRS has potential for non-invasive detection and
      follow-up of tumours in the prostate.

PMID- 9179185
TI  - The canine prostate is a spontaneous model of intraepithelial neoplasia and
      prostate cancer progression.
AB  - Increasing evidence suggests that high grade prostatic intraepithelial neoplasia
      (PIN) represents a precancerous stage in the morphologic continuum of progression
      from benign epithelium to carcinoma. In this report, we summarize our work
      characterizing the high grade PIN that occurs spontaneously in the canine
      prostate. The similarity between canine and human PIN for basal cell layer
      disruption, proliferative index, microvessel density, and its association with
      carcinoma suggest that the canine prostate may be a useful model for studying
      carcinogenesis and cancer progression.

PMID- 9179184
TI  - Growth factors mediate glucocorticoid receptor function and dexamethasone-induced
      regression of osteoblastic lesions in hormone refractory prostate cancer.
AB  - We investigated the ability of important regulators of osteoblast function, such
      as insulin-like growth factor I (IGF-I), transforming growth factor beta 1 (TGF
      beta 1), and urokinase-type plasminogen activator (uPA) to act as mediators in
      cell-cell interactions between osteoblast-like cells and metastatic prostate
      cancer cells, in vitro. In addition, we assessed whether these growth substances
      can (a) mediate glucocorticoid receptor (GR) function and (b) be implicated in
      dexamethasone-induced regression of osteoblastic tumors. Exogenous IGF-I,
      rat/human uPA, and PA-III (rat)/PC-3 (human) prostate cancer cells conditioned
      media (CM) stimulated the proliferation of rat (UMR 106 cells) and human (MG-63
      cells) osteosarcoma cells. This mitogenic activity was completely neutralized by
      anti-IGF-I specific antibody. In addition, dexamethasone decreased cell growth,
      up regulated TGF beta 1 mRNA, and down regulated uPA mRNA expression in prostate
      cancer cells. Furthermore, it inhibited cell growth by activating latent-TGF beta
      1 in osteoblast-like cells. In addition, dexamethasone down regulated the
      expression of IGF-I mRNA in osteoblast-like cells. Therefore, it is conceivable
      that uPA, TGF beta 1 and IGF-I mediate at least in part cell-cell interactions
      and GR function in osteoblastic metastases. Conceivably, regression of the
      osteoblastic tumors produced by high-dose dexamethasone treatment in hormone
      refractory prostate cancer patients is been mediated by differential regulation
      of growth factors, locally.

PMID- 9179186
TI  - Gene therapy of prostate cancer: p53, suicidal genes, and other targets.
AB  - Prostate tumor initiation and progression to malignancy may involve upregulation
      of the androgen receptor known to stimulate prostate cell proliferation; other
      etiologic mechanisms may include dysfunction of the apoptotic pathway but also
      deregulation in signal transduction and control of the cell cycle in prostate
      tissue; such abnormalities could arise from overexpression or mutations in a
      number of oncogenes or down-regulation by inactivating mutations, allelic loss,
      or other epigenetic mechanisms in tumor suppressor genes. The advantages and
      drawbacks of various delivery systems (retroviral, adenoviral, liposomes) used
      for human gene therapy are being considered. Several ex vivo and in vivo as well
      as cell culture studies are suggested for the therapy of the human prostate
      cancer using transfer and expression of genes that might be implicated in
      prostate carcinogenesis especially of the tumor suppressor p53. Expression of
      suicidal genes in prostate cancer cells using prostate-specific promoter and
      enhancer elements as well as targeting of the androgen receptor or the insulin
      like growth factor genes with triplex technology in prostate cancer cells and
      their metastases, is expected to be of therapeutic value.

PMID- 9179187
TI  - Long-term follow-up of stages T2-T3 prostate cancer pretreated with androgen
      ablation therapy prior to radical prostatectomy.
AB  - OBJECTIVE: Our previously reported non-randomized clinical trial proved the
      ability of preoperative androgen ablation therapy (AAT) to decrease positive
      surgical margins and to down stage a subset of biopsy proven stage T3 cancer.
      This study focuses on progression of disease in this group over a 4-5 year
      period. MATERIALS AND METHODS: This study group consisted of 258 consecutive
      radical prostatectomies that evolved into three groups: 1) 124 patients with
      clinical stage T2b-c cancer given AAT; 2) 118 patients with clinical stage T2a
      not given AAT; 3) 16 patients with proven stage T3 by TRUS guided biopsy and
      given AAT. RESULTS: Comparison of AAT (n = 140) to no AAT (n = 118) resulted in
      positive surgical margin rates of 15.3% vs. 49.2%. Specimen confined disease had
      tumor progression as measured by serum prostate specific antigen of 16.9% (15/89)
      for AAT (pC.001) vs 10% (5/49) for no AAT (p = 0.288). For known stage T3/C,
      43.8% (7/16) downstaged, and 85.7% (6/7) were free of disease at 46.7 mos (mean).
      The 56.3% with nonconfined (persistent) cancer after AAT had progression usually
      by one year. CONCLUSION: Neoadjuvant androgen ablation therapy before radical
      prostatectomy decreased by 3-fold the rate of positive surgical margins (+SM).
      The vast majority of these patients with +SMs were treated with either external
      beam radiation or AAT. A near two fold increase of specimen confined disease was
      found in those given AAT (p < .001). However, the rates of progression (16.9% and
      10.2% respectively) were greater in the AAT though not statistically significant
      (p = 0.288).

PMID- 9179189
TI  - Pulmonary metastases in metastatic prostate cancer: host tissue-tumor cell
      interactions and response to hormone therapy.
AB  - Stage D2 prostate cancer patients with pulmonary metastases and absence of
      detectable metastases in bones are quite rare and almost always show accompanying
      favorable and long-term clinical response to hormone therapy. We present a case
      of a patient with pulmonary metastases caused by prostate cancer who experienced
      13-year complete clinical response to GnRH analogues and we discuss the possible
      implications of host tissue-metastatic cancer cell interactions in pulmonary
      metastases and clinical response to hormone depletion therapy.

PMID- 9179188
TI  - Cryosurgery of prostate cancer. Use of adjuvant hormonal therapy and temperature
      monitoring--A one year follow-up.
AB  - OBJECTIVE: To determine the clinical outcomes at one year of Stages T2-T3
      prostate cancer by cryosurgery utilizing pretreatment with total androgen
      ablation therapy and temperature monitoring to control the freezing process.
      Study Group To date, 347 patients have had 356 cryosurgical procedures, 280 have
      reached one year post treatment. Of these 131 had re-evaluation with prostatic
      biopsy and serum PSA. METHODS: Transrectal ultrasound (TRUS) measurement of tumor
      size and biopsy of extraprostatic space was used to stage patients into two main
      groups: confined (66.6%) versus nonconfined (19.3%). Radiation failures (14.1%)
      formed a separate group. Failure rates for the 131 men include all cancer
      diagnosed during the one year period following cryosurgery. RESULTS: The one year
      failure rate for the study group was 19.8% (26/131). For stages T2a, T2h C, T3
      and radiation failures, the rates of positive biopsies were 13.9%, 12.9%, 33.3%
      and 35%, respectively. For those with local control of cancer (negative biopsy),
      80% had prostate specific antigen (PSA) levels of < 0.5 ng/ml. The statistical
      variables for persistent cancer with prostate specific antigen > 0.5 ng/ml were:
      sensitivity of 66.7%, PPV of 16.7%, NPV of 98% and specificity of 83.7%. A
      statistically significant difference exist between stages T2 vs T3 and radiation
      failures (p = < 0.5). Major complications of rectal fistula and total
      incontinence for previously non-treated cancer versus radiation failures were
      0.33% and 8.7% respectively, a 26 times greater risk. CONCLUSION: Results of
      cryosurgery for all stages of prostate cancer at one year are encouraging, being
      80% free of disease (biopsy and prostate specific antigen). The morbidity of the
      previously non-treated cancers from this procedure for us was minimal with high
      patient acceptance. For radiation failures a local control rate of 65% was
      achieved. However, early in our experience significant morbidity did occur and
      our enthusiasm for attempted salvage was initially tempered.

PMID- 9179190
TI  - Expression of metallopanstimulin and oncogenesis in human prostatic carcinoma.
AB  - BACKGROUND: We have previously shown that human metallopanstimulin (MPS-1) is a
      9.4-kDa multifunctional ribosomal S27/nuclear "zinc finger" protein which is
      expressed in a wide variety of actively proliferating cells and tumor tissues.
      Furthermore, we have shown that detection of MPS-N immunoreactive material in
      sera corresponding to the NH2 terminus of MPS-1 provides a method for determining
      the presence of certain types of abnormal proliferative conditions and/or active
      oncogenic processes in patients. In this study, we investigated MPS-N and MPS-N
      like antigens present in the blood of patients with prostatic carcinoma (PC) and
      their relationship to the clinical status of patients with PC. METHODS: The
      presence of MPS-N immunoreactive material was determined using a sensitive and
      specific radioimmunoassay (RIA) which has been developed to measure circulating
      levels of MPS-N antigen(s). In addition, MPS-N levels were compared to the
      primary bio-marker used in PC patient management, Prostatic Specific Antigen
      (PSA). RESULTS: MPS-N concentrations were determined in the blood of 107 males
      having no evidence of PC, and in 126 patients diagnosed with PC. In patients, not
      having PC the MPS-N levels were lower than 10 ng/mL. In untreated patients having
      PC stages T1/T2, the MPS-N level range was 10-30 ng/mL; in stages T3/T4 the MPS-N
      level range was 30-50 ng/mL; and in stage Mlb (distant metastasis to the bones)
      the MPS-N levels were extremely high (> 50 ng/mL). In Mlb patients that did not
      respond to therapy, the MPS-N levels remained very high (> 50 ng/mL). In Mlb
      patients that went into remission after treatment, the MPS-N levels were
      dramatically reduced. In addition, a comparison of the test properties of MPS-N
      and PSA for prostate cancer were evaluated in a total of 231 patients. In both
      the low and high value range, both MPS-N and PSA appear to be equally effective
      in modifying the probability of the target condition-prostatic cancer.
      CONCLUSIONS: These findings show that (1) in untreated PC patients, the increase
      in serum MPS-N correlated with the stage of the disease; (2) MPS-N tumor marker
      predicted the degree of aggressiveness of tumor growth and response to therapy.
      In summary, despite the uncertainties of the relative contributions of the
      molecules being measured in cancer patients (authentic MPS-1, and MPS-N-like
      protein sequences), the MPS-N test is a pragmatic test that correlates well with
      active prostatic malignancy.

PMID- 9179191
TI  - Free and total serum PSA values in patients with prostatic intraepithelial
      neoplasia (PIN), prostate cancer and BPH. Is F/T PSA a potential probe for
      dormant and manifest cancer?
AB  - Free and total PSA serum concentrations were retrospectively measured in 106
      subjects: 45 patients with intraepithelial prostatic neoplasia (PIN), 30 subjects
      with benign prostatic hypertrophy (BPH) and 31 subjects with untreated prostatic
      carcinoma. The (F/T) x 100 PSA value is recorded in subjects with the elevated
      total PSA level (> 4 ng/ml). PIN patients were divided into two groups: a low
      grade PIN (PIN 1) and high grade PIN (PIN II-III) patients. The mean (F/T) x 100
      PSA value in low grade PIN patients was 27.9 +/- 16.2 (range 17.1-41.2, median
      25.1) and has been numerically similar to the respective value in BPH subjects
      (29.1 +/- 13.2, 15.8-48.0, 27.7). These parameters differed markedly (P < 0.01)
      from the mean (F/T) x 100 PSA value in high grade PIN patients (16.9 +/- 9.0,
      range 9.9-24.9, median 16.5). The later values were in turn comparable (P > >
      0.05) with the respective value measured in untreated prostate cancer patients
      (14.4 +/- 10.8, 6.6-21.4, 12.6). Hence, values derived from the measurement of
      free and total serum PSA level may distinguish low grade PIN that prevailingly
      remains latent disease from high grade PIN that is in most cases not only early
      prostatic carcinoma but that is often a precursor of an aggressive neoplasm. The
      published literature is incoherent regarding the influence of tumor spread on F/T
      PSA level. The cutoff point that divides BPH from cancer may depend on tumor
      stage. We have not investigated F/T PSA values related to different stages and
      grades of prostate cancer. The cutoff point of (F/T) x 100 PSA in our study that
      divides malignant from benign prostate, or latent from manifest cancer, was
      tentatively assigned as 18 with a specificity of 91% and selectivity of 69%. Our
      data are based on the application of the CIS assay that, according to the
      literature, gives higher F-PSA % compared to other respective kits.

PMID- 9179192
TI  - Models for cancer skeletal metastasis: a reappraisal of Batson's plexus.
AB  - While skeletal metastasis in prostate cancer is a major and frequent
      complication, literature data on the mechanisms involved are quite confusing.
      Recent efforts, however, to establish appropriate animal models for skeletal
      metastasis have finally yielded positive results which may provide clarity in
      this discussion. Models involving both human prostate cancer cell transplantation
      in nude mice as well as syngeneic rat models have contributed to the accumulated
      evidence in favor of the hypothesis of Batson. According to this hypothesis,
      prostate tumor cells reach the vertebral venous plexus of the spine especially
      under transient conditions of increased intraabdominal pressure and lead to
      metastatic tumor deposits in the vertebrae. Animal models displaying skeletal
      metastasis in conjunction with analysis of pathological findings have been
      instrumental in validating this concept. It is to be expected that such animal
      models will contribute to the development and optimization of new treatment
      approaches for prostate cancer bone metastasis.

PMID- 9179193
TI  - Mast cell-tumor cell interactions: for or against tumour growth and metastasis?
AB  - This review comes up with the possible association between mast cells and tumour
      progression and summarizes some of the most recent data on the subject. The
      accumulation of mast cells around tumour areas is a very old observation.
      However, the functional significance of such phenomenon is a subject of
      controversy because of contradictory experimental data. In this review, two
      hypotheses are suggested. The first, refers on the possibility that the
      accumulation of mast cells is part of a general immunological host-defense
      reaction since, mast cells have been shown to be cytotoxic for some tumours
      (especially those sensitive to tumor necrosis factor-alpha). However, if such
      hypothesis is correct, one should explain why in most clinical and experimental
      cases, tumours continue to progress although the high incidence of such immune's
      system cells. We are therefore brought to consider a second possibility, in
      which, mast cells products could promote tumoural growth and metastasis. In fact,
      it is well documented that heparin, combined to a range of heparin-binding
      factors such as bFGF or TGF beta is able to promote neovascularisation, and that
      mast cell proteases cause cell structural alterations and loss of the
      extracellular matrix integrity. The role of histamine secreted by mast cells is
      less clear. There is indeed controversial experimental data referring to
      histamine's content within tumoural tissues and to histamine's proper effect on
      tumour expansion. Finally, this review discuss the mechanisms resulting to mast
      cell accumulation around tumours and more particularly the contribution of
      tumoural cells.

PMID- 9179194
TI  - Stromal fibroblasts are required for PC-3 human prostate cancer cells to produce
      capillary-like formation of endothelial cells in a three-dimensional co-culture
      system.
AB  - The outcome of patients with prostate cancer is largely dependent on the ability
      of the primary tumor for local invasion, angiogenesis and metastasis. To better
      understand the cell-cell interactions that participate in prostate cancer
      neovascularization, we have developed a novel three-dimensional co-culture
      system. Capillary-like structures were induced in fibrin gel in which collagen
      gels containing fibroblasts and/or PC-3 human prostate adenocarcinoma cells were
      sandwiched together. In the presence of collagen-embedded fibroblasts,
      angiogenesis apparently occurred, while endothelial cells did not survive when
      only PC-3 cells were embedded in collagen. In contrast, when PC-3 cells were
      combined with fibroblasts in collagen gel an enhanced formation of capillary-like
      structure formation was noted, particularly using FGF-2-supplemented medium. In
      addition, we observed morphological evidence of PC-3 cells and fibroblast
      invasion into fibrin using this system. Therefore, we conclude that fibroblasts
      apparently play an important role in angiogenesis and tumor invasion.
      Furthermore, this novel three-dimensional co-culture is apparently a promising
      model for studying de novo angiogenesis and tumor invasion in vitro.

PMID- 9179195
TI  - Radiolabeled ligands for imaging the muscarinic-cholinergic receptors of the
      heart and brain.
AB  - Interest in the potential use of cerebral SPECT and PET imaging for determination
      of the density and activity of muscarinic-cholinergic receptors (mAChR) has been
      stimulated by the changes in these receptors which occur in many neurological
      diseases. In addition, the important involvement of mAChR in modulating negative
      inotropic cardiac activity suggests that such receptor ligands may have important
      applications in evaluation of changes which may occur in cardiac disease. In this
      paper, the properties of several key muscarinic receptor ligands being developed
      or which have been used for clinical SPECT and PET are discussed. In addition,
      the ORNL development of the new iodinated IQNP ligand based on IQNB and the
      results of in vivo biodistribution studies in rats, in vitro competitive binding
      studies and ex vivo autoradiographic experiments are described. The use of
      radioiodinated IQNP may offer several advantages in comparison to IQNB because of
      its easy and high yield preparation and high brain uptake and the potential
      usefulness of the "partial" subtype selective IQNP isomers. We also describe the
      development of new IQNP-type analogues which offer the opportunity for
      radiolabeling with positron-emitting radioisotopes (carbon-11, fluorine-18 and
      bromine-76) for potential use with PET.

PMID- 9179196
TI  - The development of estrogen and progestin radiopharmaceuticals for imaging breast
      cancer.
AB  - BACKGROUND: The presence of receptors for estrogens and progestins in many breast
      tumors provides a means for imaging these tumors using positron emission
      tomography (PET) with appropriate fluorine-18 labeled estrogen and progestin
      radiopharmaceuticals. In this context, the estrogen analog 16 alpha
      [18F]fluoroestradiol (FES) has already proven to be an effective imaging agent
      for estrogen receptor-positive tumors. METHODS: Clinical studies comparing FES
      images with those based on the metabolic probe 2-[18F]fluoro-2-deoxyglucose (FDG)
      in patients before and after tamoxifen hormone therapy are underway. Several
      fluorine-18 labeled progestins have been prepared, and efforts are underway to
      develop methods for labeling steroid receptor imaging agents with the widely
      available radionuclide technetium-99m, using both pendant and integrated
      approaches. RESULTS AND CONCLUSION: Breast tumor imaging with FES and FDG shows
      an interesting relationship between tumor metabolic response (assessed with FDG)
      and tumor estrogen receptor levels (assessed with FES). The fluorine-18 labeled
      progestins show excellent target tissue selective distribution in experimental
      animals and are ready for imaging studies in humans. The development of steroids
      labeled with technetium-99m poses special challenges because of the metallic
      nature of this radioisotope.

PMID- 9179198
TI  - Comparison of MIBG and pentetreotide scintigraphy in children with neuroblastoma.
      Is the expression of somatostatin receptors a prognostic factor?
AB  - BACKGROUND: Neuroblastoma (NB) is the fourth most common pediatric malignancy and
      recent reports suggest a prognostic role of somatostatin receptor scintigraphy
      (SRS) in this disease. MATERIALS AND METHODS: Twenty two patients (pts. mean age
      43.9 months) with NB were investigated by 1-123-MIBG and SRS (In-111
      pentetreotide). Twenty-seven comparative scans were evaluated and compared for
      catecholamin excretion, Ultrasound, CT and MRI data. The patients were then
      divided into three groups. I: patients with manifest disease, II: patients with
      relapse or minimal disease and III: patients with no evidence of disease.
      RESULTS: MIBG and SRS scans were concordant in 85% (12 true positive, 7 true
      negative, 4 false negative). In 4 pts only the MIBG scan was positive. In 9 pts
      with stage I-III disease or complete remission no relapse was recorded during
      19.8 months. In 4 out of 5 pts who died SRS failed to localize the tumor sites
      but three MIBG scans were positive. Five out of 6 pts with a relapse free
      interval of 7.9 months had positive SRS and MIBG scans. CONCLUSIONS: in NB SRS
      can be applied as a specific imaging modality. However, in some pts SRS failed
      due to the lack of receptor expression. Somatostatin receptor expression seems to
      be related with a more favourable clinical outcome.

PMID- 9179197
TI  - Sigma-receptor imaging by means of I123-IDAB scintigraphy: clinical application
      in melanoma and non-small cell lung cancer.
AB  - Scintigraphy with 1123-N-(2-Diethyl aminoethyl) 4-Iodobenzamide (I123-IDAB), a
      radiolabeled benzamide, has recently been introduced to visualize sigma receptors
      in vivo. In this study we evaluated the potential clinical applicability of I123
      IDAB scintigraphy in patients with melanoma and in patients with non-small cell
      lung carcinoma (NSCLC); tumors in which sigma receptors are expressed. Twenty-six
      patients with a history of malignant melanoma and 8 patients with proven NSCLC
      were studied. Whole body scintigraphy was performed 4-5 hours after the injection
      of 170 MBq of I123-IDAB. All patients with ocular lesions and those with NSCLC
      underwent SPECT imaging of the head or thorax, respectively. For other patients
      additional spot- and or SPECT scans of suspected regions were acquired if
      necessary. Three patients with a history of malignant melanoma were considered to
      be in complete remission. None presented abnormalities on the I123-IDAB
      scintigraphy. In 20 of the 23 patients (87%) with proven melanoma, lesions were
      identified on the I123-IDAB scintigraphy. On a lesion site basis the sensitivity
      averaged 64% (43/67) Lesions located in the liver and those originating from an
      amelanotic melanoma could not be detected, while a sensitivity of 89% was
      observed for ocular sites when SPECT was used. In patients with NSCLC all primary
      lesions showed an increased uptake of tracer, but only 4 out of 18 (22%)
      mediastinal lymph nodes that were suspected radiologically. I123-IDAB
      scintigraphy can be used to visualize melanoma and NSCLC lesions in vivo. In
      malignant melanoma this may be useful to confirm the melanoma nature of lesions
      that are not easily accessible to biopsy. Differences in sensitivity between the
      various sites however must be kept in mind when interpreting the I123-IDAB
      scintigraphy. In patients with NSCLC the value of I123-IDAB SPECT is at least
      questionable.

PMID- 9179199
TI  - Comparison of In-111 pentetreotide, Tc-99m (V)DMSA and I-123 mlBG scintimaging in
      neural crest tumors.
AB  - Three radiolabelled substances, 111In-pentetreotide, 99mTc-(V)DMSA and 123I-MIBG
      with different kinetics but similar tumor seeking behavior, were i.v. injected to
      assess and correlate their clinical value in metastatic malignant
      pheochromocytomas (4 patients), stage III and IV neuroblastomas (7 patients) and
      medullary thyroid carcinomas (6 patients). All II pheochromocytoma/neuroblastoma
      patients received i.v. a dose of III MBq (3 mCi) of 123I-MIBG and 185 MBq (5 mCi)
      of 111In-pentetreotide, within approximately weeks each other. Furthermore, in 4
      of these patients as well as in all medullary thyroid carcinoma patients 111 MBq
      (3 mCi) of 99mTc-(V)DMSA were applied i.v. I week prior to the pentetreotide/mlBG
      scans. Four patients (malignant pheochromocytoma) with a total of 7 foci showing
      MIBG accumulation had 3 sites with pentetreotide and 1 site with (V)DMSA uptake,
      while in 7 patients (neuroblastora) with 15 foci showing MIBG accumulation 10
      sites had detectable pentetreotide and 3 sites detectable (V)DMSA. Of the three
      radiotracers, 111In-pentetreotide used for somatostatin receptor identification
      holds promise mainly in cases where foci imaged with 123I-MIBG are negative.
      111In-pentetreotide is unlikely to replace 123I-MIBG as a first-line routine
      diagnostic scintigraphic modality; compared to pentetreotide or MIBG, (V)DMSA
      seems to be highly sensitive only in medullary thyroid carcinomas.

PMID- 9179200
TI  - Somatostatin receptor scintigraphy of non-neuroendocrine malignancies with 111In
      pentetreotide.
AB  - In-111 pentetreotide is a new radiolabelled [OctreoScan 111, Mallinckrodt Medical
      BV, Petten] somatostatin analog with high affinity to somatostatin receptors
      (SR). introduced for the in vivo imaging of SR positive tissues. In an attempt to
      evaluate its clinical usefulness for tissue characterization in malignancies
      without neuroendocrine expression in parallel with histological and radiological
      examinations, specific scintigraphy was performed on brain (6 cases), thyroid (6
      cases) and breast (9 cases) tumors, and in lymphomas (9 cases) and melanomas (6
      cases). A dose of 111MBq of In-111 pentetreotide was injected i.v. to each
      patient and scintimages at 6 and 22 hours (for comparison) p.i. were obtained.
      The primary lesion of the breast cancer population was imaged in all 9 cases as
      well as all the palpable axillary nodes in 4 cases. Three women with impalpable
      axillary lymph nodes scanned negative but had a positive biopsy. Both meningiomas
      were positive for SR scans: positive results were also obtained for the high
      grade astrocytoma and the craniopharyngioma: Two out of 6 patients with papillary
      thyroid cancer showed a marked radiotracer accumulation. Scintigraphy in all 5
      lymphomas was positive for SR but did not detect the Tc-99m sulphur microcolloid
      [Lymphoscint, Solco, Basel, Suitzerland] imaged lymph nodes in 5 melanomectomized
      patients. When judging the imaging results of these non-neuroendocrine
      malignancies definite conclusions should not be drawn since the number of studied
      cases polymorph, was small for every cancer histotype; nevertheless SR
      scintigraphy does not seem to be reliable for tumor staging in non-neuroendocrine
      malignancies, but is more suitable for a tissue characterization and monitoring
      changes of SR expression during and after therapy.

PMID- 9179201
TI  - Value of 99m-Tc MIBI and 99m-Tc(V) DMSA scintigraphy in evaluation of breast mass
      lesions.
AB  - Among several investigative methods currently undergoing evaluation for the
      differentiation of biological features of breast mass lesions, mammoscintigraphy
      with different radiopharmaceuticals appears promising. This study evaluated the
      efficacy of 99m-Tc MIBI and 99m-Tc(V) DMSA mammoscintigraphy in the detection of
      malignant focal breast lesions. Mammography, ultrasonography, 99m-Tc MIBI and 99m
      Tc(V) DMSA mammoscintigraphy were performed in 51 women with palpable breast mass
      lesions. Following surgical removal of the abnormalities, histological
      examination revealed 40 malignant and 11 benign breast mass lesions. In
      mammoscintigraphy, early (5 minute p.i. of MIBI, 2 hours p.i. of DMSA) and late
      (2 hours p.i. of MIBI and 5 hours p.i. of DMSA) planar images of the breast and
      the axillary regions were evaluated visually and quantitatively. The efficacy of
      the methods was assessed via ROC curves and variance analysis. The visual scores
      and the quantitative T/NT values with MIBI demonstrated a significant difference
      between malignant and benign breast mass lesions. A significant difference was
      also found as concerns the grade of malignancy from the MIBI accumulation. The
      late MIBI images seemed optimal. The DMSA values indicated no relationship with
      the breast lesion malignancy. In the detection of metastatic lymph node
      involvement the sensitivity and specificity with mammography and ultrasonography
      were 57% and 85%, with MIBI 53% and 81%, and with DMSA 53% and 95%, respectively.
      It is concluded that MIBI (2 hours p.i.) mammoscintigraphy is a useful and simple
      method for differentiation of malignant breast abnormalities from benign lesions
      and for determination of the grade of malignancy. DMSA mammoscintigraphy appears
      superior to MIBI only in the detection of axillary lymph node metastases.

PMID- 9179202
TI  - Technetium-99m sestamibi imaging in the detection of axillary lymph node
      involvement in patients with breast cancer.
AB  - BACKGROUND: The status of the axillary lymph nodes is the most important
      prognostic factor in breast cancer, and the findings of axillary node dissection
      remain the gold standard for the patients staging and prognosis. The aim of this
      study was to evaluate the usefulness of Tc-99m sestamibi scintigraphy in the
      detection of axillary node involvement. MATERIALS AND METHODS: Forty-nine
      patients (age range: 32-72 years) with breast cancer were studied. Dynamic images
      (1-20 minutes post-injection of the radiopharmaceutical) followed by multiple
      planar views and tomographic images were performed. Final diagnosis was achieved
      by histology after surgery. RESULTS: Metastatic axillary lymph node involvement
      was present in 21 patients: sensitivity was 81% (17/21) for tomographic and 61.9%
      (13/21) for planar images; specificity was 92.9% (26/28) and 96.4% (27/28),
      respectively. CONCLUSIONS: Tc-99m sestamibi imaging is a promising noninvasive
      method to detect axillary node metastases in patients with breast cancer,
      tomography appears more sensitive than planar views.

PMID- 9179203
TI  - The evaluation of combined scintimammography and tumor markers in breast cancer
      patients.
AB  - BACKGROUND: Breast cancer is the second most common cancer in Thai women.
      Mammography is the method of choice for early detection but scintimammography
      (SMM) is sometimes helpful. Many tumor markers are important in the follow-up of
      treatment. MATERIALS AND METHODS: 47 breast cancer patients (36 for preoperative
      evaluation, others for postoperative investigation) were studied with SMM using
      201Tl and/or 99mTc-MIBI and serum CEA and CA15-3. RESULTS: SMM could pick up
      breast cancer in 91.7% of the patients with intact breast masses and 2/2 cases of
      local recurrence. The uptake ratio tended to increased from stage 2A through 3B.
      Sensitivity of SMM to detect axillary node uptake was only 44.4%. SMM had no role
      in the evaluation of the postoperative period unless there was no evidence of
      palpable recurrent disease. No definite correlation between serum CEA and CA15-3
      levels was observed. Elevated CA15-3 is a good indicator for recurrent and
      metastatic breast diseases and more specific than CEA in clinical correlations.
      CONCLUSIONS: SMM may be helpful when mammographic results are questionable. SMM
      can detect primary breast cancers and recurrent lesions that are palpable with
      high sensitivity. Increased tumor-uptake ratio and rising serum tumor markers,
      more often seen with elevated CA15-3 rather than CEA, could be useful for the
      prognosis of breast cancer patients. Even though CA15-3 is not reliable for the
      early detection of breast cancer, it is very helpful for monitoring therapeutic
      response since its level correlates with the clinical state better than CEA.

PMID- 9179204
TI  - 99mTc-antigranulocyte bone marrow scintigraphy of breast and prostate skeletal
      metastases.
AB  - Although bone scintigraphy using Tc-99m labelled diphosphonates is a highly
      sensitive modality for the detection of of the extent of secondary skeletal
      malignancies, it is often not sufficient since possible bone marrow participation
      cannot be imaged We make a preliminary report on the usefulness of bone marrow
      immunoscintigraphy in the follow-up of patients with skeletal metastases due to
      breast and prostate cancer in parallel with the interpretation of conventional Tc
      99m MDP bone scans. Approximately 7 to 9 months after radionuclide therapy both
      Tc-99m MDP [Hellenic Nuclear Research Center "Democritos". Aghia Paraskevi,
      Attikil and Tc-99m Anti-Granulocyte BW 250/183 [CIS Bio International, Gif sur
      Yvette, France] bone scans were performed on 2 prostate cancer patients and 5
      women with breast cancer with disseminated bone metastases. Bone scans preceded
      bone marrow scans. Bone marrow defects were concordant with cortical scans in 4
      cases, while they were larger in 4 sites compared to -MDP scan. Four sites in the
      ribs, shown on -MDP scan could not be detected on antigranulocyte scans. Bone
      cortex and marrow combined imaging of osseous metastases using different
      radiotracers increases the information on the real extent of skeletal
      involvement; the scintigraphic data obtained are valuable for the further
      decision making for the best possible management of unexpected myelosuppressive
      side effects as well as the follow-up of the treated cancer patients.

PMID- 9179205
TI  - Technetium-99m tetrofosmin scintigraphy to evaluate breast lesions.
AB  - The aim of this study is to characterise benign from malignant breast lesions by
      using 99mTc-Tetrofosmin. MATERIALS: Fifteen female patients with suspected breast
      lesions and ten normal controls underwent breast scintigraphy with 99mTc
      Tetrofosmin. All patients had conventional mammography. Breast imaging begun 20
      minutes after i.v. injection of 740 MBq 99mTc-Tetrofosmin. Patients were imaged
      in supine and prone position. Results of the 15 patients with suspected breast
      lesions, 13 showed breast uptake, and 6 of them had suspicious lesions on
      mammography. Surgery confirmed 10 carcinomas and 3 benign lesions. Two patients
      demonstrated no abnormal accumulation or suspicious findings in mammography. None
      of the normal controls had breast uptake or mammographic abnormalities. Our study
      has a sensibility of 100% and 60%, and a specificity of 80% and 100% in
      scintigraphy and mammography respectively. CONCLUSION: Our findings suggest that
      99m Tc-Tetrofosmin may play a role in evaluating breast masses and that can
      differentiate benign from malignant lesions.

PMID- 9179206
TI  - Scintimammography with technetium-99m tetrofosmin in suspected breast cancer.
AB  - BACKGROUND: Scintimammography with Tc-99m sestamibi has recently demonstrated a
      clinical usefulness in the evaluation of patients with breast lesions. The aim of
      this study was to assess the potential role of scintimammography using Tc-99m
      tetrofosmin in the detection of breast cancer. MATERIALS AND METHODS: Fifty-five
      patients (age range: 33-76 years) with suspicious breast abnormalities detected
      by mammography, and ten controls were examined. Dynamic images (1-20 min post
      injection of the radiopharmaceutical) followed by three planar views were
      performed. Final diagnosis was achieved by hystology after surgery or excisional
      biopsy. RESULTS: A total of 59 breast lesions were considered. The sensitivity of
      Tc-99m tetrofosmin scintimammography for detection of primary breast cancer was
      93.1% (27/29) and the specificity was 93.3% (28/30). No focal uptake was observed
      in both breasts of the control population. CONCLUSIONS: Tc-99m tetrofosmin
      scintimammography has high diagnostic accuracy in detecting breast cancer and may
      have a clinical role as complement to conventional mammography.

PMID- 9179207
TI  - 99mTc MIBI scintimammography with a high resolution single tube gamma camera:
      preliminary study.
AB  - 99mTc MIBI scintimammography is a sensitive and specific diagnostic technique for
      breast cancer detection when cancers more than 1 cm sized are considered. However
      the sensitivity falls in the case of submillimetric lesions. We developed a new
      Small Field of View, High Resolution Detector, able to image the breast in
      similar conditions of x-ray mammography: it allows the performance of Single
      Photon Emission Mammography (SPEM) studies. Seven patients with suspicion of
      malignant lesions were comparatively submitted to a Prone Scintimammography (PSM)
      by Anger camera and to a cranio-caudal view SPEM. The final diagnosis was reached
      by histopathology. Four malignant lesions were identified by SPEM but not by PSM,
      which that failed to image two submillimetric cancers. Both the cameras gave
      normal findings for benign lesions, confirming the high sensitivity of this
      technique. The results allow us to consider the SPEM camera as promising to
      improve scintimammographic sensitivity, even when small-sized tumors are
      examined.

PMID- 9179208
TI  - A three center study on the diagnostic accuracy of 99mTc-MIBI scintimammography.
AB  - In order to assess specificity and sensitivity of the prone scintimammography
      (PSM) in a large series with 99m-Tc MIBI, we performed a three-center study; 420
      patients were studied; after mammography all the patients were submitted to PSM
      and biopsy and/or operation. PSM was considered positive if hot spot within the
      breast was observed. In palpable masses sensitivity was 0.98 and specificity
      0.89, non palpable masses showed a sensitivity of 0.62 and a specificity of 0.91.
      When the cancers were stratified for T category the sensitivity was 0.28 in T1a
      0.26 in the group of T1a carcinomas, 0.56 in T1b 0.95 in T1c and 0.97 T2 tumors.
      Physical factors such as attenuation. Compton scattering from chest, as well as
      biological factors have a role in breast tumor imaging. In the tumors smaller
      than 1 cm biological factors are probably involved too.

PMID- 9179209
TI  - 99mTc-MIBI prone scintimammography in patients with high and intermediate risk
      mammography.
AB  - Mammographic lesions can be classified into categories of high (HR), intermediate
      (IR) and low risk of breast cancer. We have performed 99mTc MIBI
      scintimammography on 85 patients with high or intermediate risk lesions in order
      to verify its ability to diagnose cancer before biopsy. The scintimammography was
      performed in prone lateral view; all the patients were submitted to excisional
      biopsy. HR lesions showed 86% of cancers and scintigraphic accuracy of 0.81. The
      accuracy of scintimammography was 0.97 in lesions larger than 1 cm. IR lesions
      showed 47% of cancer with scintigraphic accuracy of 0.95. The scintigraphic
      sensitivity was 0.97 lesions larger than and 0.50 in lesion smaller than 1 cm,
      whereas the specificity was always about 90%. Our results suggest that
      scintimammography can substantially decrease the need of biopsy for breast cancer
      diagnosis.

PMID- 9179210
TI  - Role of thallium-201 chloride and Tc-99m methoxy-isobutyl-isonitrite (sestaMIBI)
      in evaluation of breast masses: correlation with the immunohistochemical
      characteristic parameters (Ki-67, PCNA, Bcl, and angiogenesis) in malignant
      lesions.
AB  - The aim of this project was to study the kinetics of both Tl and Tc-99m MIBI in
      PBM by evaluating tumor to normal tissue ratio in early (E) images acquired
      within 1/2 hour and delayed (D) images acquired three hours following the i.v.
      injection of 3 mCi (111 MBq) of Tl and 20 mCi (740 MBq) of MIBI on 2 separate
      days in 49 patients. The washout index was calculated from E ratio minus D ratio
      divided by E ratio. A negative ratio indicating build up of activity in D images
      and a positive ratio indicated washout of activity from the E images. In
      addition, the findings were correlated with the following immunohistochemical
      parameters: pathological grading, number of cells in mitotic division (PCNA- Ki
      67), angiogenesis (well formed and ill formed blood vessels) and presence or
      absence of Bcl 2 Oncogene (release antiapoptotic signals). Results showed that in
      all benign and malignant lesions, MIBI showed consistent washout varying from 19
      27% while with Tl, there was persistent washout in all benign lesions and mixed
      washout or buildup varying from +16% to minus 17% in malignant lesions, (E)
      ratios showed a reasonable correlation between Tl and MIBI (r = 0.5). There was
      more significant correlation between the D ratios (r = 0.8). Due to high (E) MIBI
      uptake ratios and their higher percentage of washout than Tl, delayed ratios came
      close to each other. Immunohistochemical analysis revealed benign lesions
      presented with low mitotic rate: Ki-67 (71.4%), PCNA (14.2%), low amount of ill
      formed blood vessels (42.8%) and high amount well formed blood vessels (100%).
      While malignant lesions presented with high mitotic rate Ki-67 was (96.7%), PCNA
      (100%), high amount of ill formed blood vessels (73.3% in GII and 100% in Grade
      III) and less amount of well formed blood vessels of 90% and 83.4% in Grade II
      and III respectively. Bcl-2 was variable in both benign and malignant lesions
      with 71.4% in benign, 73.4% in GII and 16.7 in GIII malignancy. In conclusion,
      early uptake ratio in both benign and malignant tumors is related to the degree
      of angiogenesis, percentage of ill formed blood vessels, high mitotic activity
      reflected by high grade of tumor and high percentage of PCNA and Ki-67.

PMID- 9179211
TI  - The role of Compton background and breast compression on cancer detection in
      scintimammography.
AB  - 99mTc MIBI scintimammography is a promising diagnostic technique for cancer
      detection. Using a dedicated Small Field Of View Gamma Camera (SFOVGC) with the
      high spatial resolution recently developed, it is possible to improve the
      sensitivity and to achieve images in projections similar to mammography with the
      breast under moderate compression. This new technique is called Single Photon
      Emission Mammography (SPEM). Several factors affect the imaging of small cancers;
      breast thickness, tumor-collimator distance and body activity. A phantom study
      was performed to assess the role of breast compression in scintimammography. In
      this work we analyze the intensity and the energy distribution of Compton
      scattering affecting the breast scintigraphy, by a Germanium detector and by
      SFOVCG. Five patients with 7 to 18 mm sized cancer were studied. The intensity of
      Compton scattering resulted from 4 to 10 times greater than true events. The
      fundamental role played by breast compression to improve the scintimammographic
      sensitivity is discussed.

PMID- 9179212
TI  - Single tube gamma camera for scintimammography.
AB  - The development of large area Position Sensitive Photo Multiplier Tubes (PSPMT)
      by Hamamatsu is opening new imaging possibilities in Nuclear Medicine. In
      particular the realization of the 8" PSPMT prototype represents the first
      important technological advantage since the discovery of the Anger Camera. PSPMT
      virtually integrates in one hundreds PMT allowing the creation of dedicated
      detectors. A Single Tube Gamma Camera based on a 5" PSPMT dedicated to
      scintimammography is presented and discussed in this work. To optimize gamma
      camera response two different scintillating arrays were tested: YAP:Ce and CsI
      (Tl). Their overall size cover all photocathode active area, and crystal pixel
      size was 2 mm x 2 mm. The detection efficiency was comparable to that of Anger
      Camera. The best result was obtained by CsI (Tl) scintillating: an intrinsic
      spatial resolution of 1.6 mm FWHM and a relative energy resolution of 17% FWHM.
      New image possibilities in scintimammography are offered by Single Tube Gamma
      Camera operating in the same radiological projection of RX mammography.

PMID- 9179213
TI  - Possible role of FDG-PET in the evaluation of urologic malignancies.
AB  - Positron-emission tomography (PET) employing 18F-labeled deoxyglucose (FDG) has
      been found to be a highly sensitive and rather specific tool in the detection of
      a variety of malignant carcinomas. Due to high resolution and outstanding image
      quality its complementary and supplementary role as compared to morphological
      methods has increasingly been acknowledged. Urinary-tract malignancies, with the
      exception of prostate carcinoma, have a rather low incidence and thus experience
      with FDG-PET is limited. We have compared the diagnostic accuracy of FDG-PET
      mainly in the primary staging of malignant testicular carcinoma, prostate and
      renal cell carcinoma. Our data indicate, that FDG-PET is more accurate in the
      detection of lymph node metastases in malignant testicular cancer as compared to
      CT, but also fails to detect micrometastases and highly differentiated teratoma.
      Its role in prostate carcinoma is questionable due to the low metabolic activity
      of this type of cancer. In all other urinary tract malignancies no final
      conclusions can be drawn, due to limited experience.

PMID- 9179214
TI  - Breast cancer detection with sestamibi-Tc-99m and Tl-201 radionuclides in
      patients with non conclusive mammography.
AB  - Early diagnosis of breast cancer using breast examination, mammography and
      ultrasonography is highly accurate, but radiologically dense breast represent a
      challenge for the mammographic detection of early stage tumors. The aim of this
      study is to determine the clinical value of scintigraphic techniques in the early
      diagnosis of breast cancer when other methods give non-conclusive results. The
      study includes 160 women with clinical suspicion of breast cancer and non
      conclusive findings in mammography, randomized either to scintigraphic scans with
      Sestamibi Tc 99m or Tl 201. Up to date, 64 women have been enrolled, 46 in Tl-201
      and 18 in Sestamibi Tc 99m. Results obtained show 73% sensitivity and 94%
      specificity with Tl 201 and 77% sensitivity and 100% specificity with Sestamibi
      Tc 99m. In this group, diagnostic accuracy improves when the tumors are bigger
      than two centimetres in diameter or when they are palpable. These preliminary
      results show that scintigraphic breast examination seems useful when other
      diagnostic methods provide non-conclusive results.

PMID- 9179215
TI  - Two phase scintigraphic mapping of lymphatic drainage in cutaneous melanoma using
      99mTc-sulfur microcolloid/99mTc antimelanoma antibody.
AB  - The purpose of lymphoscintigraphy in patients with melanoma before surgery is to
      image the lymphatic drainage net and particularly to detect the sentinel node;
      the purpose of immunolymphoscintigraphy after surgery is to map the lymphatic
      drainage and to detect a possible spead of the malignancy towards the lymph nodes
      surrounding the surgical field or more distal regions. The aim of the present
      study was to assess the sensitivity of a two-phase procedure with Tc-99m-Iabelled
      agents for exploring possible spread of melanoma after thorough resection of the
      primary lesion. Seven melanomectomized patients were enrolled into the study. The
      melanomas were situated on the head, back, arm and buttock of these patients.
      Intracutaneous lymphoscintigraphy with Tc-99m sulphur microcolloid [Lymphoscint,
      Solco, Basel, Switzerland] and i.v. immunoscrintigraphy with Tc-99m-antimelanoma
      antibody [Tecnemab-K-I, Sorin Biomedica Spa, Saluggia, Italy] at a dosage of 55
      MBq and 740 MBq respectively, were performed in 13 patients to define possible
      infiltration of lymph nodes after surgery with a time interval of 1 week between
      the two examinations. Tc-99s sulphur microcolloid preceded the Tc-99m anti
      melanoma antibody scan. The scintigrams were evaluated by three experienced
      nuclear physicians. The method detected 3 out of 16 suspicious nodes as
      malignant. Combined two-phase technique improves the diagnostic and staging
      accuracy of cutaneous melanoma affected population and appears extremely useful
      in the surgical confrontation of the lymphatic spead.

PMID- 9179216
TI  - Analysis of NK cell activity, lymphocyte reactivity to mitogens and serotest PSA
      and TPS values in patients with primary and disseminated prostate cancer, PIN and
      BPH.
AB  - In a total of 59 prostate cancer (PCa) patients, 9 patients with PIN. 29 subjects
      with BPH and 26 healthy men serum TPS and PSA values were measured together with
      NK cell activity, number and proportion of CD16+ cells, and reactivity of
      lymphocytes to mitogens (Con A. PHA and PWM). NK activity data indicate highly
      significant differences between both of patients with local tumor and those with
      disseminated disease (P < 0.01) and b) responders and nonresponding patients to
      hormonal therapy (P < 0.01). The number and proportion of CD16+ cells is lowest
      in BPH patients in comparison with controls and PCa patients. Since benign
      enlargement is attributed mainly to stromal cell proliferation in the absence of
      cell death in this compartment, gene expressions which control these events may
      participate in the surprisingly low CD16+ cell proportion. The reactivity of
      lymphocytes to mitogens (PHA. Con A and PWM) showed lower numerical values in all
      categories of PCa and BPH patients when compared with healthy men. The reactivity
      of T and B lymphocytes reported herein as immunological responses to mitogens
      (PHA. Con A and PWM) was performed 4-6 months after the beginning of therapy. Our
      data fit in well with those previously reported. Numerically lowest respective
      reactivity parameters to all mitogens were assessed in PIN subjects. Reported
      results show the specific significance of the changes in NK cell activity in
      regard with both metastatic extention of PCa and tumor response to therapy. These
      alterations match in their reliability changes with tumor marker values related
      to prostate cancer activity (TPS) and tumor differentiation (PSA). Lymphocyte
      reactivity to mitogens (Con A. PHA. PWM) may help in a subclinical discrimination
      between BPH and PIN patients that is still an important goal of clinical urology.

PMID- 9179218
TI  - Comparison of bone scanning and CA 15-3 serum concentration in the follow-up of
      breast cancer.
AB  - The follow-up bone scans (BS) of 158 women with breast cancer and without known
      bone metastases were reviewed and compared with serum CA 15-3 concentration.
      Ninety-three BS were systematic (normal serum CA 15-3) and 3 corresponded to
      proven bone metastases. Sixty-five BS were motivated:-by isolated bone pain (20
      BS. 1 corresponding to metastases),-by bone pain and signs of progression of the
      disease (11 BS. 7 corresponding to metastases: elevated serum CA 15-3 except in
      one case), by known visceral metastases (20 BS. 6 corresponding to metastases
      with elevated serum CA 15-3), by an isolated increase of serum CA 15-3 (7 BS. 4
      corresponding to metastasis) by local recurrence (7 BS. 1 corresponding to
      metastasis). These results show that bone metastases were diagnosed in 6 patients
      whose serum CA 15-3 concentration was normal. We conclude that the existence of
      normal tumor markers is not sufficient to exclude the possibility of bone
      metastases.

PMID- 9179217
TI  - Contribution of 99mTc-MIBI scintimammography to the diagnosis of non-palpable
      breast lesions in relation to mammographic probability of malignancy.
AB  - The low positive predictive value of mammography results in unnecessary biopsies.
      We present a prospective evaluation on the contribution of 99mTc-MIBI
      Scintimammography (SMM) to the diagnosis of breast cancer in 41 patients with non
      palpable breast lesions detected by mammography. In all cases mammographical
      findings were indicative of biopsy and according to the probability of malignancy
      they were classified into three groups: high probability (17), intermediate (15),
      and low (9). There were 22 malignant lesions and 19 benign. In the high
      probability group. MIBI-SMM changed the only false positive into true negative,
      and showed 2 false negatives. In the intermediate group, MIBI-SMM changed 7 of 11
      false positives on mammography into true negatives, and showed 1 false negative.
      In the low probability group MIBISMM changed 3 of the 7 false positive into true
      negatives without false negatives. In the 24 patients included in the
      intermediate and low probability groups, 10 of the 18 false positives were
      changed into true negatives by MIBI-SMM at the expense of 1 false negative. The
      addition of SMM may to reduce up to 55% of the number of unnecessary biopsies in
      non-palpable breast lesions.

PMID- 9179219
TI  - Value of 18fluoro-deoxyglucose positron emission tomography in the staging of
      recurrent breast carcinoma.
AB  - The aim of the study was to evaluate the feasibility of staging recurrent breast
      carcinoma employing fluorine-18-fluoro-2-deoxy-D-glucose (FDG) positron emission
      tomography (PET) under routine clinical conditions. In 75 patients with suspected
      recurrent or metastatic disease, whole-body FDG-PET was performed and results
      correlated with morphological imaging (CT/MRI) data and verified by histological
      findings. FDG-PET correctly identified 16 patients with local recurrence, 28 with
      lymph node involvement, 15 with bone, 5 with lung and 2 with liver metastases.
      CT/MRI identified 10 patients with local recurrences, 17 with lymph node
      involvement, 6 with bone, 5 with lung and 1 with liver metastases. FDG-PET
      detected 6 local recurrences, 8 lymph node, and 7 bone metastases, which were not
      visualized by CT/MRI. Our data provide the basis for use of FDG-PET in the whole
      body restaging of recurrent breast carcinoma in preselected patients under
      routine clinical conditions.

PMID- 9179220
TI  - Uptake of Tc-99m MIBI related to tumour size and type.
AB  - The accuracy of Tc-99m MIBI scintimammography depends on the uptake in cancer
      cells being greater than surrounding normal tissue. The aim of this study was to
      determine which were the dominant factors affecting uptake of Tc-99m MIBI in
      breast cancer cells in vivo. The tumour to background ratio (TBR) was measured in
      74 focal breast lumps occurring in 70 women, of whom 53 had breast cancer. In
      patients with breast cancer the TBR was compared in those under and over 45,
      those with tumours over and under 20 mm, those who had auxiliary disease, the
      histological type of the tumour and whether ductal on the Bloom Richardson scale.
      The only factor which appeared to have an influence on uptake of Tc-99m MIBI was
      the histological type of the tumour. Ductal carcinomas had a mean TBR of 2.07,
      significantly greater than either other types of breast cancer (TBR = 1.31) and
      benign tumours (TBR = 1.46). The histological type of tumour appears to be the
      dominant factor affecting uptake of Tc99m MIBI in vivo.

PMID- 9179221
TI  - The usefulness of technetium-99m-MIBI scintimammography in diagnosis of breast
      cancer: using surgical histopathologic diagnosis as the gold standard.
AB  - The purpose of this study was to evaluate the usefulness of 99mTc-MIBI
      scintinammography for the detection of breast cancer. METHODS: Sixty-one
      consecutive patients referred for a suspicions breast lesion on clinical
      examination were studied with 99mTc-MIBI scintimammography. There were 60 female
      patients and 1 male patient with 63 pulpable breast abnormalities. Each patient
      received 20mCi 99mTc-MIBI intravenously. Ten and 120 minutes postinjection, three
      planar views, right and left lateral prone and anterior supine thoracic views,
      were obtained. The patient underwent surgery within one week and the final
      diagnostic results (histopathology) were obtained. RESULTS: Thirty-two of 63
      abnormalities of breast were pathologically confirmed breast cancer, and 31 were
      benign lesions. In the group of patients studied, the sensitivity of 99mTc-MIBI
      scintimammography was 78.1% (25 true-positive, 7 false-negative) and the
      specificity was 90.3% (28 true-negative, 3 false positive). The positive
      predictive value was 89.3%, the negative predictive value was 80.0%, the positive
      likelihood ratio was 8.1, the negative likelihood ratio was 0.2. CONCLUSION: This
      study showed the high diagnostic accuracy of 99mTc-MIBI scintimammography in
      detecting breast cancer. 99mTc-MIBI scintimammography can be used as an assistant
      method to non-invasively assess breast cancer invasiveness before surgery.

PMID- 9179222
TI  - Rhenium-186-HEDP palliative treatment in disseminated bone metastases due to
      prostate cancer.
AB  - Prostate carcinoma is the most commonly associated with osseous metastases
      malignancy in males. The lesions, being usually of a mixed sclerotic/lytic
      variety and less often of the pure sclerotic type, need to be treated by a bone
      seeking radioactive element with an as low as possible radiobiological burden on
      the surrounding (peritumoral) tissues. Rhenium-186-HEDP was used to treat these
      osseous metastatic lesions due to its bone seeking kinetics attractive
      radiochemical properties. Of a total of 16 prostate cancer patients. 3 experiment
      loss of pain, 8 experienced obvious and 2 some improvement. No change was
      observed in 3 patients. Ten patients manifested a flare syndrome increasing pain
      approximately 2 to 6 days, after Re-186-HEDP i.v. application. Six patients
      showed a definite and 9 a slight decrease in platelet levels and absolute number
      of polymorphonuclear white blood cells, up to fourth week following treatment.
      One patient underwent a whole blood transfusion and in 2 peripheral neuropathy
      was observed lasting about 9 to 12 days. Re-186-HEDP appears to be a promising
      new metal ion complex for the palliation of painful bone metastases in prostate
      cancer. Compared to Sr-89 therapy, it shows a longer analgetic efficacy and has
      the advantage of emitting gamma rays, a fact which facilitates dosimetric
      calculations.

PMID- 9179223
TI  - Clinical aspects of local and regional tumor therapy with 188Re-RC-160.
AB  - Somatostatin-receptors have been found to be overexpressed in a variety of neuro
      endocrine and epithelial cancers. While the introduction of a long-acting
      somatostatin-analogue, octreotide, exerted mainly anti-cancer activity in neuro
      endocrine tumors, no convincing results have been demonstrated in other cancers.
      RC-160, another somatostatin-analogue has been selected because of its high
      receptor affinity and its anti-cancer activity. 188Re is a generator produced
      radionuclide with favourable gamma and beta-emission, allowing diagnostic and
      therapeutic application. The results of in vivo biodistribution and therapeutic
      outcome following systemic, intralesional and intracavitary application in animal
      studies employing 188Re-RC-160 are summarized. Safety considerations, dosimetry
      estimates and applicable indications are outlined. The clinical impacts of this
      radiopharmaceutical in cancer management are discussed.

PMID- 9179224
TI  - Renal cell carcinoma detection and systemic therapy with tumour-affine gallium-67
      and with yttrium-90 citrate solutions.
AB  - BACKGROUND: There have been no major advances in the systemic detection of renal
      cell carcinoma (RCC) and its unpredictable metastases. Surgery, thus, remains the
      mainstay of the curative treatment for the localized disease. The propose of the
      present study has been to systemically detect and treat advanced RCC respectively
      with Ga-67 and Y-90 radiopharmaceuticals containing tumour-affine species.
      PATIENTS AND METHODS: Thirty-three RCC patients were imaged with Tc-99m-MDP and
      then with Ga-67 citrate solution in order to detect RCC and its metastases.
      Yttrium-90 citrate solution, containing the radionuclide species
      chromatographically and electrophoretically identical to those in RCC-affine Ga
      67 solution, was administered i.v. for systemic therapy of advanced RCC. Total
      body distribution of Y-90 was studied with a gamma-camera equipped with an ultra
      high-sensitivity collimator. The efficacy of the therapy was studied by the
      clinical condition of the patient and by the total-body scintigraphic imaging
      with Tc-99m-MDP and with Ga-67 citrate solution. RESULTS: Ga-67 detects RCC bone
      metastases better than Tc-99m-MDP. Systemic therapy of RCC metastasized to bones,
      lung and brain was obtained with RCC-affine Y-90 citrate solution. CONCLUSIONS:
      Third group metal radionuclides, Ga-67 and Y-90, detect and treat advanced RCC.

PMID- 9179225
TI  - Radioimmunotherapy of ovarian cancer with radiolabelled monoclonal antibodies:
      biological basis, present status and future perspectives.

PMID- 9179226
TI  - Advanced prostate cancer diagnosis and therapy with gallium-67 and yttrium-90,
      respectively.
AB  - BACKGROUND: Androgen deprivation therapy remains so far the mainstay of advanced
      prostate cancer treatment. Although it improves the quality of life of the
      patient for some time, the disease progresses and soon it becomes hormonally
      unresponsive. The object of our research has been to find a systemic therapy for
      prostate cancer patients whose disease no longer responds to hormone therapy,
      radiation therapy, chemotherapy and immunotherapy. PATIENTS AND METHODS: Thirty
      one advanced prostate cancer patients with intense bone metastasis pain, bed
      ridden, and with permanent urinary catheter were first examined with Ga-67 and
      then treated with Y-90 solutions which were chromatographically and
      electrophoretically analysed for the presence of both cationic and anionic
      species of the radionuclide. The quality of life and prostate specific antigen
      (PSA values) values were followed for testing the success of the therapy.
      RESULTS: Prostate cancer-affine Y-90 cured the advanced prostate cancer patients
      who regained their normal life. The uptake of the radionuclide in the primary
      cancer and its metastases responsible for the treatment has been confirmed by
      scintigraphy. CONCLUSIONS: Prostate cancer-affine Y-90 solution, containing
      stable cationic and anionic species of the radionuclide, is effective in the cure
      of advanced prostate cancer patients.

PMID- 9179227
TI  - Yttrium-90/indium-111-DOTA-peptide-chimeric L6: pharmacokinetics, dosimetry and
      initial results in patients with incurable breast cancer.
AB  - BACKGROUND: Radioimmunotherapy (RIT) using 131I-Chimeric L6 (ChL6) antibody has
      shown therapeutic promise for patients with breast cancer. To enhance this
      potential, a novel immunoconjugate was developed that targets adenocarcinomas
      like breast cancer and tightly binds yttrium-90 (90Y) for therapy and indium-111
      (111In) for imaging. The radioimmunoconjugate consists of a macrocyclic chelator
      (DOTA) linked to ChL6 by a catabolizable peptide. 90Y-DOTA-peptide-ChL6 was
      designed to minimize the radiation dose to critical normal tissues, thereby
      improving the therapeutic index. MATERIALS AND METHODS: Three patients with
      incurable metastatic breast cancer received 90Y/111In-DOTA-peptide-ChL6 for 5
      pharmacokinetics/dosimetry studies and one of these patients also received 2
      therapy doses. Quantitative imaging of 111In and in vitro assay of 90Y and 111In
      in blood urine and bone marrow samples were obtained. RESULTS: 90Y/111In-DOTA
      peptide-ChL6 was prepared at high purity and was stable in vivo. Assays of bone
      marrow revealed no evidence for escape of 90Y or 111In from the chelate. 111In
      imaging of tumors was excellent, providing a therapeutic index for tumor to
      marrow radiation as high as 229 to 1. 90Y and 111In provided comparable
      pharmacokinetics, as did tracer and therapeutic doses of radioimmunoconjugates.
      One patients that received 2 therapeutic doses of 90Y-DOTA-peptide-ChL6 showed
      regression of tumors and tumor markers. Toxicities were relatively minor and no
      anti-globulin response developed despite 5 immunoconjugate infusions.
      CONCLUSIONS: This first study in patients of radioimmunoconjugates with a
      catabolizable linker between the metal chelator and the antibody confirmed that
      these novel 90Y/111In-DOTA-peptide-ChL6 radioimmunoconjugates have significant
      potential. Tracer doses of 111In-DOTA-peptide-ChL6 for imaging predicted the
      behavior of therapeutic doses of 90Y-DOTA-peptide-ChL6. The latter
      radioimmunoconjugate induced regression of tumors and tumor markers without
      significant toxicity. When compared to earlier 131I-ChL6 dosimetry, 90Y-DOTA
      peptide-ChL6 provided a therapeutic index several times better.

PMID- 9179228
TI  - Radioimmunotherapy for advanced breast cancer using I-131-ChL6 antibody.
AB  - BACKGROUND: The biologically active, antiadenocarcinoma monoclonal antibody
      chimeric L6 (ChL6) was labeled with 131I and administered in cycles to patients
      with metastatic breast cancer who had failed standard therapy. The therapeutic
      potential, tumor targeting and maximum tolerated dose of 131I-ChL6 were studied.
      METHODS: Ten patients with L6 reactive breast cancer received an imaging dose of
      131I-ChL6 followed 24 hours later by a therapy dose of 131I-ChL6 (20-70 mCi/m2).
      Patients received up to 4 monthly cycles unless they had significant
      myelosuppression, progression of disease, or a high human anti-mouse antibody
      titer. In vivo activation of effector cell function, complement levels and
      cytokine release were studied. RESULTS: All 10 patients had detectable cancer on
      the imaging study. In 7 patients with superficial cancer, the radiation dose was
      120 to 3700 cGy/cycle; 5-30 times higher than the whole body dose. Therapy
      resulted in minimal acute or subacute toxicity. Dose limiting toxicities were
      neutropenia and thrombocytopenia. Six of 10 patients had clinically measurable
      tumor responses; 5 had responses that lasted more than one month (1.5-5 months).
      The MTD for 131I-ChL6, given in at least two monthly doses, was 60 mCi/m2.
      CONCLUSION: Objective clinical responses were seen in five of 10 patients treated
      with 131I-ChL6. The tumor response in heavily pretreated, advanced breast cancer
      may be related to the combined effects of targeted radiation and the biological
      activity of L6/ChL6.

PMID- 9179229
TI  - Single photon emission computerized tomography increases the sensitivity of
      indium-111-pentetreotide scintigraphy in detecting abdominal carcinoids.
AB  - Somatostatin (sms) receptors have been identified in carcinoids (c), so enabling
      their visualization with 111In-pentetreotide scintigraphy. The aim of this study
      was to evaluate if single photon emission computerized tomography (SPECT) can
      increase the sensitivity of sms receptor scintigraphy in the detection of
      abdominal c. 26 patients (pts) with a present, or previously operated, abdominal
      carcinoid were submitted to SPECT over the abdomen and multiple planar views
      after the injection of 111In-pentetreotide. Magnetic resonance imaging and
      computed tomography were also performed. In 19 pts abnormal sites of uptake were
      found by SPECT which localized 13 abdominal extrahepatic (in 11 pts) and 45
      hepatic lesions (in 15 pts). No pathologic accumulation was seen in 7 pts in
      complete remission after surgery. Planar images visualized 7 abdominal
      extrahepatic (in 6 pts) and 26 liver tumor sites (in 10 pts), conventional
      procedures detected 5 abdominal extrahepatic (in 4 pts) and 36 hepatic lesions
      (in 10 pts). 111In-pentetreotide SPECT is more sensitive than planar scanning and
      conventional methods to detect abdominal c, and so may play a major role in the
      early and accurate mapping of tumour spread.

PMID- 9179230
TI  - 111In-pentetreotide detection of gastrinoma before and after surgery.
AB  - Eighteen patients with Zollinger-Ellison syndrome were studied with 111In
      pentetreotide SPECT in order to localize gastrinoma, the tumour responsible for
      this pathology. NMR imaging was also carried out. Eight patients were operated.
      111In-pentetreotide was reinjected 4 hours before operation and the radioactivity
      of the excised tumours counted. The nature of the withdrawn tissues was assessed
      by immunohistochemistry (chromogranina A). The scintigraphy was repeated 3-6
      months after surgery. 111In pentetreotide SPECT was more sensitive than NMR. It
      was also absolutely specific because all the radioactive tumours excised showed
      positive chromogranin A staining. The radioactivity/gram counted in gastrinomas
      exceeded 10 fold the hepatic and biliary radioactivity and 20-100 folds the
      radioactivity of blood and omentum. In all the operated patients but three, the
      scintigraphy performed after surgery did not detect tumours. However complete
      eradication did not occur, because though 3-6 months after surgery the
      gastrinemia was significantly lower with respect to pre-surgery results it did
      not return to normal values in all patients but two.

PMID- 9179232
TI  - Palliative therapy using rhenium-186-HEDP in painful breast osseous metastases.
AB  - The efficacy and toxicity of treatment with 1400 +/- 100 MBq of Re-186-HEDP were
      evaluated in women with osseous metastatic breast cancer. The follow-up period
      was fourteen weeks. The efficacy of treatment was assessed by a) a pain and
      performance questionnaire that patients were asked to complete daily and b) a CT
      scan comparison of a randomly preselected osseous lesion before and 30 weeks
      after Re-186-HEDP i.v. application. The response to treatment was also evaluated
      by using the Kamofsky Index. Two out of fourteen women (14%) experienced loss of
      pain, 6 experienced obvious and 2 some improvement. No change was observed in 4
      patients. Five patients manifested a flare response to treatment, with increase
      in pain within the first, 4 to 5 days after Re-186-HEDP administration. Five
      patients showed a decrease in platelet levels and absolute number of
      polymorphonuclear blood transfusion; no neurologic side effects were observed. Re
      186-HEDP appears to be a useful new radiopharmaceutical for pain palliation
      induced by osseous metastases due to breast cancer. Compared to Sr-89 chloride
      efficacy, it provides longer-lasting analgesia, and when needed it can be
      reinjected with less risk due to its improved physico- and radiochemical
      properties.

PMID- 9179231
TI  - In vivo study of a technetium labelled anti-EGFr MoAB.
AB  - Epithelial Growth Factor receptors (EGFr) are normally present in all the
      epithelial cells, but their overexpression is closely related to presence of
      cancer. We have raised EGF-competitive antibody against EGFr and have labelled it
      with 131I and technetium. The ability of this antibody to bind to A431 cells to
      be internalized has been tested on A431 cells cultures. Its ability to give
      scintigraphic images of epithelial tumors has been tested on nu/nu balb c mice
      xenografted with A431 cells. The labelled antibody is well internalized by
      cultured cells. Xenografted tumors are clearly imaged both by 131I and 99mTc anti
      EGFr Mo/Ab. 99mTc labelling is very interesting. The tumor/background ratio was
      0.72 +/- 0.2 for 99mTc and 0.40 +/- 0.6 for 131I labelling. Moreover very high
      uptake of 99mTc MoAb was obtained 2 hours after injection whereas the 131I
      antibody required 24 hours.

PMID- 9179233
TI  - Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re
      186-HEDP.
AB  - Recent advances in radionuclide therapy offer a new approach for the management
      of metastatic bone pain. This paper reports the results of dosage escalation
      studies with 186Re-HEDP as a bone-seeking radiopharmaceutical in patients with
      bone metastases originating from breast or prostate cancer with regard to
      toxicity, pharmacokinetics and bone marrow dosimetry and the palliating effect on
      bone pain. Thrombocytopenia proved to be the dose limiting factor and 186Re-HEDP
      showed a considerable efficacy in end-stage patients with metastatic bone pain.

PMID- 9179234
TI  - Gastric uptake during Re-186 HEDP bone scintigraphy.
AB  - In bone scintigraphy extraosseous uptake of the radiopharmaceutical (TcO4-,
      pertechnetate) is a common finding when the stomach is abnormally observed; this
      may be due to the instability of the radiopharmaceutical leading to free
      pertechnetate within this organ. The same explanation might be inculpate rhenium
      186-HEDP, due to its similarity to Tc-99m MDP's sphysicochemical properties and
      behavior, as both radioisotopes are Group VII metals /1/ and are labelling the
      same ligand (a diphosphonate moiety). We report on 186Re-HEDP uptake in the
      stomach in two patients with osseous metastases because of prostate and breast
      cancer respectively out of a series of 52 cancer affected individuals, treated
      with 186Re-HEDP. The thorough clinical and laboratory investigation of both
      patients assessed that this extraosseous radio-rhenium accumulation was
      multifactorial with the main cause being a disturbance of body fluid acid
      balance, favoring calcium and phosphate ion precipitation and leading to 186Re
      HEDP extraosseous uptake.

PMID- 9179235
TI  - Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188
      generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer
      treatment.
AB  - Rhenium-188 (beta- = 2.2 MeV; gamma = 155 keV; T1/2 16.9 hours) is an attractive
      therapeutic radioisotope which is produced from decay of the reactor-produced
      tungsten-188 parent (T1/2 69 days) and thus conveniently obtained on demand by
      elution from the alumina-based tungsten-188 /rhenium-188 generator system. The
      rhenium-188 is obtained as sodium perrhenate by elution of the generator with
      0.9% saline. The post elution use of disposable tandem, ion-exchange columns is a
      simple method for the concentration of rhenium-188 saline solutions with specific
      volumes > 500 mCi/ml. This method can also extend the useful shelf-life of the
      generator, which can be as long as one year. The long useful shelf-life of the
      generator is expected to provide rhenium-188 at very reasonable costs for routine
      preparation of a variety of radiopharmaceuticals for the treatment of a variety
      of cancers including breast cancer. We are evaluating two types of Re-188-labeled
      agents under investigation which have potential for the treatment of breast
      cancer. Rhenium-188-labeled hydroxyethylidenediphosphonate (HEDP) and Re-188
      dimercaptosuccinic acid (DMSA) are being applied for palliative treatment of pain
      associated with skeletal metastases, and the Re-188-RC-160 somatostatin analogue
      [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Lys-Val-Cys-Trp-NH2] for somatostatin
      receptor-positive tumors. The results of initial clinical studies with the two
      bone pain agents demonstrate good targeting to skeletal metastases, and use of Re
      188-HEDP has resulted in pain palliation with minimal bone marrow suppression in
      the initial patient studies. While these initial studies have been conducted in
      patients with prostate cancer, similar results are expected in planned studies in
      breast cancer patients. In animal studies, Re-188-RC-160 has been successfully
      used for the local/regional treatment of experimental breast cancer and other
      cancers. Re-188-RC-160 binds to somatostatin-receptor-positive cells both in
      vitro and in vivo, including breast cancer cells (ZR-75-1 breast carcinoma and
      NCI-H69 human small cell ling carcinoma), but not to binding-negative cells
      (Raji, Burkitt's lymphoma). A structurally similar Re-188-cyclic peptide with
      different binding specificity (CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr
      Pen-Thr-ol]; an opiate-receptor antagonist) did not bind to target cells. Both
      gentisic acid and ascorbic acid are present in the Re-188-HEDP and Re-188-RC-160
      formulations, and have been found to also significantly reduce radiolytic
      degradation of the somatostatin peptide analogues, and may have general
      application in the stabilization of Re-188-labeled radio-pharmaceuticals.

PMID- 9179236
TI  - External beam radiation enhances antibody mediated radiocytotoxicity in human
      glioma cells in vitro.
AB  - Enhanced accumulation of monoclonal antibodies in tumor tissue has been observed
      as a result of external beam irradiation (EBR). This effect was mainly attributed
      to increased vascular leakage due to unspecific radiation damage of vascular
      endothelial cells. The aim of this study was to investigate the effects of EBR on
      expression and antibody-binding of epidermal growth-factor receptor (EGF-R) in
      human glioma cells in-vitro. High-grade glioma cells were irradiated with
      conventional x-rays (0-3600 Rad) and surface binding, internalization and
      radiocytotoxicity of 125I-labeled monoclonal antibody (MAb) 425, specific for
      human EGF-R, was tested. EBR showed a short-term dose and time dependent increase
      of specific MAb 425 binding and internalization in receptor positive cell lines
      U87-MG and A1207. This effect was probably due to a mitotic block and an increase
      in cellular volume. Combination of EBR and 125I-425 showed additive effects on
      cell vitality/survival and was more pronounced in contact inhibited cells as
      compared to cells growing in a log-phase. We assume that cells exposed to 125I
      labeled MAb 425 are only able to accumulate a critical number of DNA double
      strand breaks when the doubling-time is prolonged e.g. under contact-inhibition
      or radiation induced mitotic blockade. We conclude that EBR has no negative
      effects on EGF-R expression, MAb-binding and internalization. The combination of
      EBR and 125I-MAb 425 enhances cytotoxic efficacy and thus supports adjuvant use
      in the clinical management of high-grade glioma.

PMID- 9179237
TI  - Pre-clinical experience with Re-188-RC-160, a radiolabeled somatostatin analog
      for use in peptide-targeted radiotherapy.
AB  - The clinical potential of radiolabeled peptides such as octreotide and VIP has
      been widely established for tumor localization. Radiotherapy based on the tumor
      binding potential of the peptides and the radiotoxic effects of beta- or a
      emitting radionuclides is an extension of such applications. Rhenium-188 (T1/2
      16.9 hr, beta-max 2.1 MeV) coupled to the analogue RC-160 has been used to
      establish the feasibility of treating tumors with radiolabeled peptides, and our
      experience with this approach is summarized. In three different experimental
      tumor models (human prostate, mammary gland, and small cell lung carcinomas) in
      nude mice, treatment resulted in significant reduction or elimination of tumor
      burden. Two routes of administration were used: intra-lesional injection
      (prostate carcinoma) and intra-cavity injection (mammary and SCLC). Re-188
      labeled negative control peptides bound to tumor cells to a low extent and did
      not exhibit therapeutic benefit. RC-160 by itself did not result in therapeutic
      benefit. Tumors which did not bind Re-188-RC-160 did not evidence a therapeutic
      benefit. Uncoupled Re-188 (control) was rapidly excreted via the urinary bladder
      and did not accumulate in either tumors or normal tissues even following direct
      injection. Instant radiolabeling kits containing 200 micrograms of RC-160 were
      labeled with < 3000 MBq of Re-188 in 30 minutes with no need for subsequent
      purification. These studies establish the conceptual feasibility of targeted
      radiotherapy based on the local or regional administration of radiolabeled
      peptides.

PMID- 9179238
TI  - Two ways to establish potential At-211 radiopharmaceuticals.
AB  - The special radiophysical characteristics of the alpha emitting cyclotron
      radionuclide At-211 favour its therapeutic application. Studies for therapeutic
      use have been carried out over the past 15 years. Labelling reactions with this
      heavy halogen and characterization of the products are important because of the
      low concentrations used in treatment (non carrier added level). One successful
      way to produce At-211 radiopharmaceuticals is the labelling of aromatic iodine
      compounds with At-211 via isotope exchange or reaction of organostannyl
      precursors with astatine. These products enter the tumour by its metabolism. To a
      certain extent, the intraarterial application of At-211 labelled particles seems
      to be a promising alternative to intravenous application, causing selective
      accumulation of therapeutic At-211 doses as shown by the first alpha
      endoradiotherapy of a incurable recurrent lingual carcinoma.

PMID- 9179240
TI  - 131I-MIBG therapy of neural crest tumours (review).
AB  - Due to its diagnostic application, consideration was given to the therapeutic
      potential of 131I-MIBG in neural crest tumours, mainly in malignant
      pheochromocytomas, paragangliomas, neuroblastomas (NB), carcinoids and medullary
      thyroid carcinomas (MTC). The therapeutic procedure consists of a) thyroid
      blockade; b) administration of high specific activity 131I-MIBG; c) single doses,
      varying from 3.7 to 9.5 GBq, given by slow i.v. infusion (2-3 hours); d)
      monitoring of the patient during the infusion of the tracer. Targeted
      radiotherapy with 131I-MIBG in malignant pheochromocytomas, paragangliomas,
      carcinoids and medullary thyroid carcinomas, was shown to be effective with
      partial reduction of tumoral lesions (mainly in pheochromocytomas with 58% of
      objective responses) and palliation in metastatic tumors; in a few
      pheochromocytomas also succeed in eradicating the residual/recurrent tumor. In
      patients with stage IV NB who failed to respond to or relapsed after conventional
      chemotherapy, MIBG therapy showed an important palliative role. A significant
      therapeutic improvement in the outcome of stage III and IV NB patients was
      obtained by introducing 131I-MIBG as a first line therapy, partial or even
      complete responses occurring in more than 60% of the cases treated. Experiences
      combining chemotherapeutic agents and 131I-MIBG are also in progress with
      encouraging results. MIBG therapy is well tolerated; toxicity is limited to minor
      hematologic toxicity and patients generally recover spontaneously. The risk of
      pancytopenia rises in patients with bone and/or bone marrow metastases; in these
      cases bone marrow harvesting is recommended. An alternative approach to 131I-MIBG
      therapy in MTC uses radiolabeled monoclonal antibodies. A novel immunotargeting
      method, which includes a bispecific antibody and 131I as a radiolabel, seems to
      be very promising.

PMID- 9179239
TI  - Treatment of lymphoid cell malignancy with In-114m labelled autologous
      lymphocytes.
AB  - This paper is a preliminary report of a clinical trial for the treatment of
      patients with refractory chronic lymphocytic leukaemia, using autologous In-114m
      labelled lymphocytes. Fourteen patients have been treated so far with doses
      ranging from 69 to 211 MBq. All patients had progressive low grade NHL, resistant
      to chemotherapy and conventional radiotherapy. Following the intravenous
      administration of radiolabelled autologous lymphocytes 53% (range 33-92%) of the
      activity accumulated in the spleen, 35% (21-64%) in the liver and 5% in the bone
      marrow. The initial response in all patients was a rapid decrease in lymphocyte
      count in peripheral blood. 10 of the 14 (72%) patients showed a response to the
      treatment. In 2 patients, there was a complete response which lasted 24 and 36
      months respectively, 8 patients showed a partial response of 2 to 17 months
      duration. None of the patients experienced any subjective toxicity although
      myelosuppression was seen in all patients. This is a novel concept for the
      administration of therapeutic radiation in a selective way for the treatment of
      lymphoid cell malignancy and has produced significant antitumour effect in
      patients with highly resistant disease. The trial is ongoing and a full report
      will be published on its completion.

PMID- 9179241
TI  - Effects of induction of multi-drug resistance on accumulation of 99mTc-sestamibi
      in vitro.
AB  - The aim of our study was to evaluate the speed of induction of drug-resistance
      and its effects on intracellular MIBI accumulation in established human cell
      lines in-vitro. Four out of 5 cell lines were sensitive to vincristine, 1 cell
      line was vincristine-resistant. All vincristine sensitive cell lines became
      vincristine-resistant following drug exposure. Resistance in low-drug
      concentrations occurred as early as 24 hours after exposure and progressed to a
      roughly 1000-times enhanced resistance within 7 days. Induction of drug
      resistance was associated with significantly decreased MIBI accumulation in 2
      cell lines but was uneffected in 1 cell line, that was primarily drug sensitive
      as well as in one cell line that was primarily drug-resistant. Our data indicate,
      that induction of MDR is an extremely rapid process and the development of drug
      resistance is not always associated with enhanced MIBI extrusion.

PMID- 9179242
TI  - Effects in the testes after SPECT myocardial perfusion with Tl-201 or Tc-99m
      hexaMIBI.
AB  - Thallium-201 with a half-life of 73 hours, decays by electron capture and as a
      consequence emits numerous Auger electrons. When it localises in the cell nucleus
      it causes enhanced biological effects. Technetium-99m with a half-life of 6
      hours, radiates gamma rays and the side effects are not as significant. Tl-201
      and Tc-99m labelled with SESTAMIBI are used for the SPECT perfusion image of the
      heart. In this study the tissue of interest are the testes which, after
      irradiation, can develop stochastic effects: both somatic (cancer) and
      hereditary. The activities of the radiopharmaceuticals used in common practice
      (30 mCi of Tc-99m and 3 mCi of Tl-201) cause different probabilities for the
      induction of stochastic effects in the testes. The probabilities are about 30
      times higher for Tl-201 than for Tc-99m. These results, in combination with the
      fact that the higher activity of Tc-99m yields better images within shorter time,
      must make the clinician carefully assess the choice of the radiopharmaceutical to
      be used for the studies of the heart, especially for patients of reproductive
      age.

PMID- 9179243
TI  - Prediction of tumor absorbed dose by Tc-99m-MDP scintigraphy prior to treatment
      with Sr-89.
AB  - A first order approximation of the tumor absorbed dose prior to treatment with Sr
      89 was attempted in three patients treated for metastasized prostate carcinoma.
      All patients underwent bone scanning with Tc-99m-MDP two days before the
      administration of Sr-89, and a number of sequential quantitative images were
      obtained over the first 8 hours after Tc-99m-MDP injection. The collected data
      were used to derive an individualized Sr-89 time retention curve. Dosimetric
      estimations were subsequently based on the model described by ICRP Publ.30
      (1979). In the present study a simplified model for the kinetics of both Sr-89
      and Tc-99m-MDP was assumed. Normal adult data on the retention time of the two
      radiopharmaceuticals in the whole skeleton were combined and a linear
      relationship was derived between the time required for the same percentage uptake
      of the two radiopharmaceuticals after a single injection. The same relationship
      was assumed to hold for metastatic sites. The estimated absorbed dose in the
      principal metastases of the three patients, as well as normal bone of the same
      type and volume, is reported. A first order approximation of the absorbed dose by
      the skeleton is provided by the proposed method, before the therapeutic
      application of Sr-89 chloride using a diagnostic Tc-99m-MDP bone scan. The method
      is useful, simple, inexpensive and can be routinely performed.

PMID- 9179244
TI  - Stump the experts. Case. Myxoid liposarcoma.

PMID- 9179245
TI  - Repair of defects of the nasal ala.
AB  - BACKGROUND: Alar defects present a reconstructive challenge. OBJECTIVE: To define
      closure options for alar defects of variable thickness and location. METHODS: The
      repair options for closure of alar defects are reviewed and discussed with regard
      to depth of defect and complexity of reconstruction. CONCLUSION: Surgeons
      repairing defects of the nose should develop a variety of reconstructive
      approaches for the ala including but not limited to those presented here.

PMID- 9179246
TI  - Fast healing after laser skin resurfacing. The minimal mechanical trauma
      technique.
AB  - BACKGROUND: Laser resurfacing is rapidly becoming a widely used method of skin
      ablation for cosmetic improvement. The technique with which the instrument is
      used can make the difference between obtaining the desired result with a benign
      postoperative period and one with unnecessary complications. OBJECTIVE: This
      paper describes a technique that maximizes the benefits while minimizes the risks
      in using this highly advanced instrument. METHODS: We have limited the areas
      where multiple passes are done to areas that have rhytides; for the rest of the
      skin a single pass is done and the final carbonized eschar is not removed.
      RESULTS: Faster healing and less complications. Shorter operative and anesthesia
      times. Greater patient acceptance and satisfactory cosmetic results. CONCLUSIONS:
      This technique provides a safer, faster, and satisfactory cosmetic results with a
      much smaller possibility of the complications seen with conventional methods.

PMID- 9179247
TI  - Treatment of nevus spilus with the Q-switched ruby laser.
AB  - BACKGROUND: Q-switched lasers have shown to be effective in the removal of
      unwanted cutaneous pigmentation. Benign cutaneous pigmented lesions represent a
      heterogeneous group. Nevus spilus is a relatively uncommon pigmented lesion
      characterized by dark, hyperpigmented dots scattered over a tan-colored macule.
      OBJECTIVE: A cohort of patients with nevus spilus was studied to determine the
      effects of Q-switched ruby and Q-switched Nd:YAG laser treatment on clearance of
      pigment and to evaluate potential side effects. METHODS: Six patients with nevus
      spilus were treated with the Q-switched ruby laser (QSR). In addition, three
      lesions received a test treatment with the Q-switched Nd:YAG (QSYAG) laser at 532
      or 1064 nm. The results of treatment were documented during follow up visits.
      RESULTS: Most lesions showed a near-complete or complete response to laser
      treatment. In one case partial hyperpigmentation occurred after treatment and in
      one case no follow-up could be obtained. In the three cases that received both
      QSR and QSYAG laser treatment, the QSR laser was shown to be the most effective
      in removing pigment. CONCLUSION: Nevus spilus can be treated effectively with the
      Q-switched ruby laser.

PMID- 9179248
TI  - Manual resurfacing and trichloroacetic acid for the treatment of patients with
      widespread actinic damage. Clinical and histologic observations.
AB  - BACKGROUND: A facial resurfacing regimen combining manual abrasion of the skin
      and 25% trichloroacetic acid has been reported to produce excellent results, but
      the histologic depth of injury produced by this technique has not been studied.
      OBJECTIVE: To describe our experience with this technique treating patients with
      extensive actinic damage and to determine the histologic depth of injury
      produced. METHOD: We treated 40 patients using manual resurfacing and
      trichloroacetic acid, primarily for widespread actinic keratoses. Resurfacing
      tools included silicone carbide sandpaper, drywall screen, electrocautery tip
      cleaners, abrasive pads, scalpel blades, and curettes. Four patients underwent
      sequential biopsies to evaluate the depth of wounding using this technique.
      RESULTS: Manual resurfacing combined with trichloroacetic acid consistently
      produced excellent cosmetic results and nearly complete eradication of actinic
      keratoses. Histologically, treated areas showed replacement of the dermal
      elastotic band by newly formed collagen, a significantly deeper level of wounding
      than the Jessner's/35% trichloroacetic acid peel. There was no evidence for
      foreign body granulomas clinically or histologically as a result of the abrasive
      materials. CONCLUSIONS: The deeper level of this peel explains the improved
      cosmetic outcome and greater eradication of actinic keratoses. This treatment is
      particularly well suited for patients with extensive photodamage and widespread
      actinic keratoses.

PMID- 9179249
TI  - Intraoperative and postoperative bleeding problems in patients taking warfarin,
      aspirin, and nonsteroidal antiinflammatory agents. A prospective study.
AB  - BACKGROUND: Many patients who undergo cutaneous surgery take medications that can
      affect bleeding. The role of these medications in postoperative bleeding
      complications is unclear. Dermatologists have no clear guidelines regarding the
      need to discontinue these medications preoperatively. OBJECTIVE: We designed a
      prospective study to evaluate the incidence of postoperative bleeding
      complications in patients taking aspirin, warfarin, or nonsteroidal
      antiinflammatory agents. METHODS: Data were collected from patients undergoing
      Mohs surgery regarding preoperative medication history, operative bleeding, and
      postoperative bleeding. Frequency of postoperative bleeding complications was
      then evaluated. RESULTS: There was no statistically significant difference in
      postoperative bleeding complications between patients on aspirin, warfarin, or
      nonsteroidal antiinflammatory agents, when compared with controls. CONCLUSION: It
      may not be necessary to discontinue aspirin, warfarin, or nonsteroidal
      antiinflammatory agents in patients undergoing many common dermatologic surgical
      procedures, such as Mohs surgery.

PMID- 9179250
TI  - An assessment of the suitability of Mohs micrographic surgery in patients aged 90
      years and older.
AB  - BACKGROUND: One option for the treatment of cutaneous tumors in the very elderly
      has been simple observation. However, the combination of an increasing elderly
      population and a concomitant high incidence of skin cancer will make this problem
      more common. OBJECTIVE: To assess the suitability of Mohs micrographic surgery as
      a treatment modality for skin cancer in the 90 years and older age group.
      METHODS: A group of patients who underwent Mohs surgery from January 1988 to
      August 1996 aged 90 years and older was identified, and tumor type, site,
      comorbid medical conditions, medications, and surgical complications were
      recorded. RESULTS: A total of 106 basal cell carcinomas (BCCs), 33 squamous cell
      carcinomas (SSC), six melanomas, and one basosquamous carcinoma were resected
      from 115 patients with an average age of 92.4 years. The overall ratio of BCC/SCC
      was 3.2 BCCs occurred most commonly on the face; SCCs were found more frequently
      on the cheeks. Patients had an average of 1.9 comorbid medical conditions and
      took an average of 2.3 regular medications. One complication occurred.
      CONCLUSION: Mohs surgery is a safe and effective therapy for those over 90 years
      of age.

PMID- 9179251
TI  - Lower eyelid reconstruction using pedicled skin flap and palatal mucoperiosteum.
AB  - BACKGROUND: Full-thickness lower eyelid reconstruction requires functional as
      well as aesthetic considerations to be successful in the long term. The three
      elements necessary for a stable result are skin, mucosa, and a semirigid
      "skeleton" to provide the support that prevents the development of ectropion. A
      number of techniques combining these elements are described in the literature,
      with reconstruction in one or more stages. OBJECTIVE: We report a simple method
      of reconstruction of a full-thickness lower eyelid defect, in which palatal
      mucoperiosteum provided both the mucosal and the "skeletal" components following
      tumor excision. METHODS: Literature review and report of illustrated case.
      RESULTS: A cosmetically acceptable result with no functional deficit or donor
      site morbidity. CONCLUSION: Palatal mucoperiosteum provides an abundant supply of
      tissue that may be used successfully in the reconstruction of the lower eyelid.
      It functions both as a mucosal lining in addition to a semirigid supporting
      framework.

PMID- 9179252
TI  - Tumescent liposuction issues.

PMID- 9179253
TI  - Conservative management of aplasia cutis congenita.

PMID- 9179254
TI  - Postoperative syncope after office surgery.

PMID- 9179255
TI  - Silicone gel sheeting for the management of hypertrophic and keloid scars: the
      mechanism of its action.

PMID- 9179256
TI  - Use of ABD pads in liposuction.

PMID- 9179257
TI  - Interpositional dressing for reduced postoperative pain after laser skin
      resurfacing.

PMID- 9179258
TI  - Anesthesia for lip augmentation.

PMID- 9179259
TI  - The surgical pathology report: standardizing the "gold standard".

PMID- 9179260
TI  - p53 protein immunoexpression in esophageal squamous cell carcinoma and adjacent
      epithelium.
AB  - BACKGROUND: Immunoreactivity for p53 tumor suppressor gene product is commonly
      found in human malignancies and some premalignant lesions, but its role in cancer
      development and its value as a marker of tumor biologic behavior is still
      unclear. OBJECTIVES: This study was undertaken to assess p53 immunoexpression in
      esophageal squamous cell carcinoma and attempts to determine its correlation with
      morphological features associated with tumor behavior. METHODS:
      Immunohistochemical study was performed on archival paraffin-embedded tissue of
      37 esophageal squamous cell carcinomas and respective adjacent mucosa. RESULTS:
      Twenty-one tumors (56.8%) demonstrated specific staining for p53. Sixteen areas
      of dysplasia were present in 14 out of the 35 cases. p53 positivity was found in
      one low-grade dysplasia and in six high-grade dysplasias. By univariate analysis,
      p53 immunoexpression correlated positively with local invasion (P = 0.01) and
      perineural spread (P = 0.04). Multivariate analysis with logistic regression
      showed that tumor invasion was the only factor that discriminated between p53
      positive and p53 negative cases (OR: 15.6, P < 0.02). No relationship was found
      between p53 expression and tumor grade, DNA nuclear ploidy, and S-phase fraction.
      CONCLUSIONS: These data suggest that p53 dysfunction may be implicated in early,
      preinvasive, stages of esophageal cancer as well as in the tumor progression
      related to a more invasive phenotype.

PMID- 9179261
TI  - Influence of cathepsin D expression in lung adenocarcinoma on prognosis: possible
      importance of its expression in tumor cells and stromal cells, and its
      intracellular polarization in tumor cells.
AB  - BACKGROUND: Cathepsin D, an aspartic lysosomal proteinase, has been described to
      be closely associated with tumor progression and prognosis in some human
      malignancies. The purpose of this study was to determine clinicopathological and
      prognostic significance of cathepsin D expression in lung adenocarcinoma.
      METHODS: Expression of cathepsin D in 152 lung adenocarcinoma patients was
      immunohistochemically studied using the antihuman cathepsin D antibody. RESULTS:
      Eighty patients (53%) showed negative immunoreactivities in tumor cells. The
      cathepsin D-positive patients (72 patients, 47%) were divided into two subgroups;
      granular type expression (48 patients, 31%) with its polarized expression mainly
      in the luminal side of the cytoplasm of tumor cells and basal type expression (24
      patients, 16%) with its polarized expression mainly in the basal or infranuclear
      side of the cytoplasm. Patients with basal type expression showed significantly
      more marked scar formation (P = 0.042), and especially among the patients with
      stage I disease, those with basal type tended to show poorer prognosis (P =
      0.071) than the others. Cathepsin D was also expressed in stromal cells within
      the tumor tissues, and 86 patients (57%) with moderate to massively infiltrating
      cathepsin D-positive stromal cells showed a lower grade of differentiation (P =
      0.005) and higher scar grade (P = 0.0003) than those with few cathepsin D
      positive stromal cells. Cathepsin D status in stromal cells was significantly
      associated with prognosis (P = 0.014), and in a multivariate analysis, its
      expression status in stomal cells was marginally an independent prognostic factor
      only among the stage I patients. CONCLUSIONS: In determining significance of
      cathepsin D expression in this disease, it is important to consider separately
      its expression cell type and its polarization pattern in tumor cells within the
      tumor tissue. How ever, only cathepsin D status in stromal cells within the tumor
      tissue is a marginal marker influencing prognosis among stage I patients.

PMID- 9179262
TI  - Effect of surgical experience on results of esophagectomy for esophageal
      carcinoma.
AB  - BACKGROUND: Esophagectomy for esophageal cancer is associated with substantial
      operative morbidity and mortality. The effect of surgical experience on results
      of esophagectomy has received little attention in the medical literature.
      METHODS: A retrospective review of esophagectomies for cancer was done. RESULTS:
      Seventy-four patients underwent esophagectomy by 20 different surgeons. Three
      surgeons performed 6 or more esophagectomies per year ("frequent" surgeons),
      whereas the other 17 surgeons performed 5 or fewer esophagectomies per year
      ("occasional" surgeons). Forty-two patients were operated on by frequent
      surgeons. There were 3 (7%) anastomotic leaks and no deaths. In 32 patients
      operated on by occasional surgeons, there were 7 (22%) anastomotic leaks and 7
      (22%) operative deaths. The anastomotic leak rates were not significantly
      different (P < .07), but frequent surgeons had a significantly lower operative
      mortality (P < .0014). CONCLUSIONS: Esophagectomy for esophageal cancer should be
      performed by experienced esophageal surgeons with sufficient yearly volume of
      procedures to maintain competence.

PMID- 9179263
TI  - Abnormal expression of four novel molecular markers represents a highly
      aggressive phenotype in breast cancer. Immunohistochemical assay of p53, nm23,
      erbB-2, and cathepsin D protein.
AB  - BACKGROUND: In view of the cumulative results to date, p53, nm23, erbB-2, and
      cathepsin D are the most promising investigational prognostic factors in breast
      cancer. OBJECTIVES: The clinical utility of these molecular markers to predict
      recurrence was evaluated. METHODS: Archival pathology tissues of 100 breast
      cancer patients were analyzed by immunohistochemical assay. Molecular biologic
      data were merged with clinicopathologic variables. RESULTS: Thirty-two patients
      (32%) had recurrence of disease at a median follow-up of 48 months (range 26-72
      months). Investigational factor expression had statistical correlation for
      recurrence with increasing coexpression: one variable 20.6%, two variables 34.2%,
      three variables 47.1%, four variables 80.0% (P = 0.003). In univariate analysis,
      lymph node metastasis, tumor size, erbB-2 protein overexpression, and loss of
      nm23 protein expression were significant variables to determine recurrence; in
      multivariate analysis, node status and tumor size emerged as the most significant
      variables for recurrence. CONCLUSIONS: Coexpression of the studied
      investigational variables functioned as significant prognostic correlates for
      recurrence. These findings suggest that the studied investigational prognostic
      factors possess the ability to discriminate a highly aggressive phenotype in
      breast cancer.

PMID- 9179264
TI  - Thoracic esophageal carcinoma above the carina: a more formidable adversary?
AB  - BACKGROUND: Prognosis with esophageal carcinoma above the carina is generally
      thought to be the worst without any conclusive demonstration. METHODS:
      Clinicopathologic features of 101 patients with thoracic esophageal carcinoma
      above the carina (AC group) were compared with those of 665 patients with a tumor
      below this level (BC group). RESULTS: The number of T4 tumor was significantly
      larger in the AC group (P < 0.001). Survival curve for all patients in the AC
      group was significantly worse than the BC group (P < 0.001). Survival in patients
      who underwent any treatment other than esophagectomy was equally bad in the two
      groups. However, survival in patients undergoing esophagectomy was similar in the
      two groups (P = 0.64), with the cumulative 5-year survival rates of 44.5% and
      43.1%, respectively. Even in patients with metastatic disease in the lymph nodes,
      the cumulative 5-year survival rates after radical esophagectomy were similar.
      CONCLUSIONS: The prognosis of patients in the AC group is generally worse than
      the BC group because of the close anatomical relationship with the
      tracheobronchial tree. However, radical esophagectomy is recommended for patients
      at stages less advanced than T4.

PMID- 9179265
TI  - Identification of women with T1-T2 breast cancer at low risk of positive axillary
      nodes.
AB  - BACKGROUND AND OBJECTIVES: The diagnostic and therapeutic significance of
      axillary dissection has been questioned. We sought to define a subgroup of
      patients with early-stage breast cancer who are at low risk for positive axillary
      nodes. METHODS: Between 1970 and 1995, 1,598 women with stage I and II breast
      cancer underwent level I-II axillary dissection with a minimum of 10 nodes
      removed. The following factors were examined in univariate analysis for
      predicting positive nodes: race, method of detection, location of the primary
      tumor, age, menopausal status, obesity, ER status, PR status, pathologic tumor
      size, lymphatic vascular invasion, tumor grade, and histology. RESULTS: Four
      hundred and forty-five of the 1,598 patients (27.8%) had histologically positive
      axillary nodes. Significant factors in univariate analysis for positive nodes
      included: tumor size, lymphatic vascular invasion, grade, method of detection,
      primary tumor location, and age. The only group of women with a 0% risk of
      axillary nodes were those in whom the pathologic tumor size was < or = 5 mm and
      mammographically detected. A 5-10% risk of positive axillary nodes was identified
      in women with (1) pathologic tumor size 6-10 mm, mammographically detected, and
      age < or = 40 years, and (2) tubular carcinoma < or = 10 mm. Tumors detected on
      physical examination with or without mammography and women < or = 40 years had a
      significantly increased risk of nodes. In multivariate analysis lymphatic
      vascular invasion (P < 0.001), method of detection (P = 0.026), location (P =
      0.01), and pathologic tumor size (P = 0.002) were significant predictors of
      positive axillary lymphadenopathy. CONCLUSIONS: The decision to forego an
      axillary dissection should be considered in (1) tumors mammographically detected
      and < or = 5 mm (2) mammographically detected, pathologic size 6-10 mm, age > 40
      and (3) tubular carcinoma < or = 10 mm. All other groups had a > 10% risk of
      nodes and may benefit from axillary dissection.

PMID- 9179266
TI  - Monitoring during cryosurgery of bone tumors.
AB  - BACKGROUND: Cryosurgery is used in orthopaedic oncology as adjuvant treatment
      after intralesional excision of bone tumors to induce cell death at and beyond
      the surgical margin. Monitoring freeze/thaw cycles during cryosurgery is
      beneficial in controlling a cryosurgical procedure and in preventing an
      unwarranted local extent of the freeze. METHOD: We conducted a study of 15
      cryosurgical procedures with the use of a protocolized temperature measuring
      system wit peroperative graphic visualization. RESULTS: Using a liquid nitrogen
      spray, intralesional temperatures of -150 degrees C were achieved, which are,
      according to the literature, associated with cell death. Extralesional
      temperature measurements showed no sub-zero temperatures of surrounding important
      tissues. CONCLUSIONS: Temperature recordings in and outside the lesion during
      cryosurgery in orthopaedic oncology are of importance to monitor the freeze/thaw
      cycles and are helpful in facilitating an effective cryosurgical procedure and in
      controlling the extent of the freeze, avoiding local complications.

PMID- 9179267
TI  - Proliferating cell nuclear antigen expression in the gallbladder with
      pancreaticobiliary maljunction.
AB  - BACKGROUND AND OBJECTIVE: To clarify the histogenesis of cancer of the
      gallbladder of the patients with pancreaticobiliary maljunction (PBMJ), the
      proliferating cell activity of the epithelium of gallbladder was examined.
      METHODS: A total of 21 patients with pancreaticobiliary maljunction [8 with
      gallbladder cancer (MCA group) and 13 without cancer (M group)] were studied
      using immunohistochemical staining with a monoclonal antibody to the
      proliferating cell nuclear antigen (PCNA). The 23 gallbladder cancer patients
      without PBMJ (CA group) and 10 patients with normal gallbladders (N group) were
      also examined as controls. RESULTS: The PCNA-positive rates of non-cancerous
      epithelium of the gallbladder in patients with PBMJ (14.2% in MCA group and 11.6%
      in M group) were significantly higher than those without PBMJ (3.9% in CA group
      and 1.5% in N group). CONCLUSION: The high proliferating cell activity of
      epithelium of the gallbladder may be an explantation for the high incidence of
      gallbladder cancer in patients with pancreaticobiliary maljunction.

PMID- 9179268
TI  - Enteropathy-associated T-cell lymphoma: a case report with radiographic and
      computed tomography appearance.
AB  - We report a case of enteropathy-associated T-cell lymphoma (EATL) of the jejunum
      in a 56-year-old man. The patient suffered for several years from nonspecific
      abdominal complaints, with no clinical evidence of malabsorption. The patient
      underwent extensive imaging procedures including barium meal and computed
      tomography. Computed tomography of the abdomen showed small mesenteric lymph
      nodes and an area of intestinal wall thickening. Barium meal demonstrated a short
      jejunal stricture. Histology revealed lymphoma of the jejunum, with microscopic
      changes distant from the lesion consistent with celiac disease. The spectrum of
      EATL ranges from patients with frank celiac disease, to patients with only
      immunohistochemical evidence of celiac disease, who develop small bowel lymphoma.

PMID- 9179269
TI  - Wide margin resection and brachytherapy for post-irradiation breast cancer
      recurrence.

PMID- 9179270
TI  - Extended lymph node dissection in gastrointestinal cancer.
AB  - We reviewed the literature concerning the effect of extended lymph node
      dissection on survival in patients with gastrointestinal cancer. Most
      retrospective and/or prospective nonrandomized comparative studies have claimed
      that extended lymph node dissection significantly improves survival rate in
      patients with esophageal cancer, gastric cancer, and colorectal cancer. However,
      it is difficult to interpret these results since specialized care provided in
      trials may itself improve survival. In gastric cancer, several prospective
      randomized trials have failed to demonstrate a survival advantage of extended
      dissection, while there are few well-done prospective randomized trials in
      esophageal or colorectal cancer. Therefore, the therapeutic value of extended
      lymph node dissection remains to be determined in gastrointestinal cancer.
      Randomized prospective studies within the bounds of the ethical treatment of
      patients can and should be done.

PMID- 9179271
TI  - Radiation biology in brachytherapy.
AB  - The biological rationale for the use of brachytherapy, which is undergoing a
      significant resurgence in the United States, is reviewed with emphasis on low
      dose rate (LDR brachytherapy). Some of the newer alternatives that have recently
      been developed, such as pulsed dose rate (PDR) brachytherapy, are discussed.

PMID- 9179272
TI  - Why is age such an important independent prognostic factor in acute lymphoblastic
      leukemia?
AB  - Despite the use of similar intensive chemotherapy regimens, adults with acute
      lymphoblastic leukemia (ALL) exhibit a strikingly inferior outcome when compared
      to children. Mirroring this difference in prognosis, childhood and adult ALL
      exhibit distinctive age-related differences in potential etiologic factors and
      underlying biology. Childhood ALL mostly occurs in industrialized countries, with
      a unique peak in incidence between the ages of 2 and 8 years. It is associated
      with features conferring a favorable response to therapy, including early pre-B
      cell disease and a hyperdiploid karyotype or a cryptic t(12;21) translocation.
      The lymphoblasts of childhood ALL appear to arise in a developmental compartment
      that is "poised" for apoptotic death and are particularly sensitive to
      glucocorticoids, antimetabolites, and other cytotoxic agents. In contrast, adult
      ALL commonly possesses the poor-prognosis Philadelphia chromosome and is often
      drug-resistant. A far higher proportion of adults with ALL present with high
      initial white blood cell count and high-risk immunophenotypes, and exhibit a slow
      induction of remission with greater therapy-related toxicity. Improved supportive
      care measures with current intensive therapies and the development of novel
      leukemia-targeted biotherapies will be required to improve the cure rates of
      adults with ALL.

PMID- 9179273
TI  - Molecular subsets and prognostic factors in acute lymphoblastic leukemia.
AB  - Leukemia is a heterogeneous collection of diseases with different molecular
      origins. The molecular features may provide physicians with markers that can be
      used to monitor disease. In acute lymphoblastic leukemia (ALL), molecular
      monitoring methods can be very useful in developing and improving treatment. Some
      argue that one of the main problems in adult ALL is that it is homogeneous but,
      in fact, it is a very diverse condition. However, it can't be seen in the surface
      markers or in the nucleus of these diseases, so there is a need to develop ways
      to identify these cases. Good and potentially curable subsets of ALL patients are
      beginning to be identified by combining traditional phenotypic and immunologic
      markers with molecular and genetic approaches. As treatments improve, definition
      of therapeutic and prognostic subsets and their significance to clinical outcome
      is imperative. While progress has been made in the use of molecular techniques to
      detect residual disease, we must still acquire experience in using these markers
      to monitor treatment efficacy, with the eventual aim of improving outcome.

PMID- 9179274
TI  - Bone marrow transplantation in first remission.
AB  - The allogeneic bone marrow transplant experience for acute myeloid leukemia (AML)
      is broader than that for acute lymphocytic leukemia (ALL). However, data
      describing disease-free survival in AML in first remission in the range of 40% to
      65% are almost identical to the data from larger studies of ALL in first
      remission. Similarly, the published allogeneic transplant data for ALL in second
      remission are comparable to those in the AML experience. The efficacy of
      autologous stem-cell transplantation for ALL, while promising, remains unproven
      in first remission, and larger multicenter studies are underway to answer this
      question. Until prospective randomized trials of bone marrow or peripheral-blood
      stem-cell purging have been performed, a conclusion that ex vivo bone marrow
      transplantation is of clinical benefit for any patient with ALL will be
      impossible. Such studies will be difficult to conduct and, in an autologous
      setting, should include genetic marking to help determine whether reinfused
      leukemic cells will lead to relapse.

PMID- 9179275
TI  - Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL).
AB  - The ability of T cells that accompany or develop from transplanted allogeneic
      marrow to eradicate leukemia has been repeatedly demonstrated in animal models.
      Whether a similar graft-versus-leukemia effect exists in humans who have received
      transplants for acute lymphoblastic leukemia can be addressed by five different
      clinical observations: comparisons of autologous versus allogeneic
      transplantation, comparisons of syngeneic versus allogeneic transplantation,
      examination of relapse rates in allogeneic recipients who do or do not develop
      GVHD, the impact of T-cell depletion on relapse rates, and the results of donor
      lymphocyte infusions to treat posttransplant relapse. The bulk of available
      evidence supports the view that a potent GVL effect exists in patients treated
      for ALL. These results provide a strong rationale for efforts to develop
      techniques to further capitalize on the GVL effect.

PMID- 9179276
TI  - The role of allogeneic bone marrow transplantation in the treatment of high-risk
      acute lymphocytic leukemia in adults.
AB  - Studies in the last decade show that most adults with acute lymphocytic leukemia
      (ALL) can achieve remission with intensive induction chemotherapy. Depending on
      the risk factors present at diagnosis in an individual patient, continued
      remissions range from less than 10% to more than 50%. The following factors have
      been shown to be predictive of relapse: high white cell count at diagnosis, age
      beyond 30, extramedullary disease at presentation, unfavorable chromosomal
      translocations, time longer than 6 weeks to enter remission, and use of less
      intensive chemotherapy for induction. Studies have been conducted to determine
      whether allogeneic bone marrow transplantation (BMT) could improve the outcome
      for patients with high-risk ALL when performed during first remission. These
      studies have shown that these patients have a 40% to 60% chance of disease-free
      survival. The current recommended strategy for patients with high-risk ALL in
      first remission is to undergo bone marrow transplantation prior to relapse. For
      those in second and subsequent remissions or those who do not achieve remission,
      allogeneic BMT still offers the best chance for cure of the disease.

PMID- 9179277
TI  - Bone marrow transplantation for acute lymphocytic leukemia (ALL).
AB  - Patients with high-risk acute lymphocytic leukemia (ALL) in first complete
      remission, or those with relapsed leukemia, are unlikely to have their disease
      controlled by conventional therapeutic approaches. Bone marrow transplantation
      has been shown to produce extended leukemia-free survival for a substantial
      number of patients, making it the preferred treatment approach. However,
      differential availability, transplant-associated mortality, and antileukemic
      efficacy of various transplant options makes the choice between donor-cell
      sources problematic. Currently, patients can have transplantation therapy using
      either autologous marrow cryopreserved with or without purging, allogeneic
      related-donor, or umbilical-cord blood cells used for reconstitution. Transplants
      with autologous marrow or related-donor marrow can be undertaken with relative
      speed. In contrast, searching for an available unrelated living donor and the
      logistics of arranging for a donor harvest requires several months. Use of
      umbilical cord blood is more expeditious and may greatly accelerate the
      availability of unrelated allogeneic autotransplants and in the safety of
      unrelated-donor transplantation are needed to improve outcomes of transplantation
      in patients with ALL. Consideration of speedy availability, transplant-associated
      toxicity, and antileukemic efficacy of these varying options all need to be
      balanced for effective clinical decisions on transplant treatment in patients
      with ALL.

PMID- 9179278
TI  - Risk-adapted treatment of adult acute lymphoblastic leukemia (ALL).
AB  - Modern intensive chemotherapy programs have identified several important
      prognostic factors for treatment outcomes in adult acute lymphoblastic leukemia.
      This has allowed clinicians to tailor treatment regimens designed specifically
      for the various patient subgroups. Of adult ALL patients, 75% have B-lineage
      disease, and certain biologic characteristics in these patients, including older
      age and the incidence of mediastinal and CNS disease, differentiate them from T
      cell patients. Most of the high-risk cytogenetics are found in the B-lineage
      group, making cytogenetics the single most powerful prognostic factor in ALL
      after failure to respond to initial treatment. Currently, there is no subgroup of
      ALL patients in which standard chemotherapy can be described as adequate, and
      improved treatment is needed for all groups of patients. These improvements will
      come from prospective randomized trials. At this time, allogeneic transplant
      remains the treatment of choice for high-risk ALL.

PMID- 9179279
TI  - Treatment of adult patients with relapsed or refractory acute lymphoblastic
      leukemia (ALL).
AB  - Relapsed acute lymphoblastic leukemia (ALL) in an adult is rarely cured. The
      majority of adult patients with relapsed ALL who are subsequently cured of their
      disease are given chemotherapy to achieve a second complete remission (CR)
      followed by a successful allogeneic bone marrow transplant. Overall, only a
      minority (typically 10% to 20%) of these relapsed patients in second CR are cured
      of their disease by an HLA-identical sibling allogeneic transplant. Many
      chemotherapy reinduction protocols have been tested in the setting of relapsed
      ALL. High-dose regimens appear to result in a greater incidence of second CRs
      compared with reinduction with standard vincristine, prednisone, anthracycline
      based regimens. A combination of high-dose Ara-C (HDAC) and an anthracycline has
      the greatest likelihood of achieving a first CR in ALL patients with refractory
      disease or a second CR in relapsed patients. We have recently explored the
      activity of HDAC combined with a single a high dose of an anthracycline
      (idarubicin) or an anthracenedione (mitoxantrone) in adult patients with ALL. Our
      results indicate that these regimens are extremely active in the
      relapsed/refractory setting as well as in previously untreated adults. In order
      to compare this approach with standard therapy for ALL, we have started to accrue
      patients to a phase III trial, which will prospectively randomize patients to
      induction with Ara-C and high-dose mitoxantrone versus a standard vincristine,
      prednisone, anthracycline-based regimen.

PMID- 9179281
TI  - Use of cytokines in the treatment of acute lymphoblastic leukemia.
AB  - Placebo-controlled and/or historically controlled trials have shown that
      granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor (GM-CSF) enhance neutrophil recovery rates and occasionally
      reduce the rate and duration of infection. Some data appear to support an
      advantage with GM-CSF in reducing the incidence of fungal infections.
      Immunomodulation with cytokines such as interferon or interleukin-2 may prove to
      be of benefit in the management of acute leukemia when used in combination or
      sequence with chemotherapy.

PMID- 9179280
TI  - Biologic response modifiers in acute lymphoblastic leukemia.
AB  - Despite the presence of tumor antigens, the paucity of clinically significant T
      cell mediated immune responses against human tumors is striking. This may, in
      part, be because of the inability of cancer cells to function as efficient
      antigen-presenting cells. For full activation, T cells must receive two signals
      delivered by antigen-presenting cells. The first is antigen-specific and is
      delivered by presentation of antigenic peptide by the major histocompatibility
      complex molecules to the T-cell receptor. This signal, although necessary, is in
      itself insufficient to mediate T-cell activation, cytokine release, and
      subsequent T-cell proliferation and function. For full T-cell activation, T cells
      require delivery of a secondary, costimulatory signal, such as that delivered by
      members of the B7 family to their receptor on the T-cell, CD28. Delivery of an
      antigen signal in the absence of costimulation does not result in productive
      immunity, but rather in anergy, a state of antigen-specific T-cell
      nonresponsiveness. To induce T-cell proliferation against B-cell malignancies,
      the tumor cell must first be induced to express B7 or the tumor antigen must be
      presented by an efficient antigen-presenting cell. Simple expression of B7 on the
      tumor cell alone, however, cannot reverse anergy. Reversal of anergy is a complex
      process involving stepwise repair of the T-cell defect and can be accomplished by
      prolonged exposure to interleukin-2, signaling through the CD2 pathway, followed
      by antigen presentation with B7-mediated costimulation. Successful
      immunotherapeutic strategies in the B-cell malignancies will likely require steps
      to reverse established anergy in the tumor-bearing host as well as effective
      tumor-antigen presentation.

PMID- 9179282
TI  - Treatment of fungal and other opportunistic infections in immunocompromised
      patients.
AB  - Significant improvements have been made with regard to infection-related
      mortality in patients with underlying immune deficiencies. Many factors
      predispose these patients to infection, including the incidence of profound and
      persistent neutropenia, but with resolution of the immune suppression the
      majority of these patients will survive their neutropenic period. Although most
      initial infections are caused by bacterial pathogens, most subsequent infections
      are due to fungal organisms. The mortality rate continues to be very high for
      immunocompromised patients who develop infection with Candida and Aspergillus.
      Fungal infections remain difficult to diagnose; antifungal therapy alternatives
      are inadequate, and these infections remain a major prevention and treatment
      challenge for immunocompromised patients. For the future, novel approaches that
      improve standard therapy, incorporate cytokines and growth factors, or focus on
      preventive measures offer the most effective way to deal with fungal infections.

PMID- 9179283
TI  - ALL and beyond: implications for other hematologic malignancies.

PMID- 9179284
TI  - Cloning, overexpression, and mutagenesis of the gene for homoprotocatechuate 2,3
      dioxygenase from Brevibacterium fuscum.
AB  - Homoprotocatechuate (hpca, 3,4-dihydroxyphenylacetate) is a central intermediate
      for the bacterial degradation of aromatic compounds. Homoprotocatechuate 2,3
      dioxygenase (HPCD) catalyzes the key ring cleavage step in the metabolism of hpca
      by the Gram (+) bacterium Brevibacterium fuscum to yield alpha-hydroxy-delta
      carboxymethyl cis-muconic semialdehyde. A genomic DNA library of B. fuscum was
      constructed in Escherichia coli using a cosmid vector and screened by spraying
      the cells with hpca. One clone was found to contain the gene for HPCD based on
      its ability to convert hpca into the yellow-colored product. This cosmid clone
      was further subcloned and the gene for HPCD was localized and sequenced. The open
      reading frame codes for a protein with 365 amino acids and M(r) = 41,699, in
      accord with the characteristics of the previously purified wild-type enzyme. The
      gene for HPCD was overexpressed in E. coli to approximately 30% of the total
      soluble protein, and purification of the recombinant enzyme to apparent
      homogeneity was achieved by a two-step procedure. Iron was the only abundant
      metal found in the purified recombinant enzyme, and the specific activity per
      iron was comparable to that observed for the wild-type enzyme. The deduced amino
      acid sequence of HPCD has a very high level of homology (78.6% identity in the
      337-aa overlap) to the manganese-dependent homoprotocatechuate 2,3-dioxygenase
      (MndD) from Arthrobacter globiformis CM-2. The basis for the difference in metal
      selection by HPCD and MndD was investigated by mutagenesis of a 50-base-pair
      region of the HPCD gene containing three frame shifts relative to the MndD gene.
      The purified triple mutant of HPCD did not exhibit a significant change in the
      metal content; therefore, other factors must contribute to the selection of the
      active site metal.

PMID- 9179286
TI  - Large-scale preparation of two new ribosome-inactivating proteins--cinnamomin and
      camphorin from the seeds of Cinnamomum camphora.
AB  - An improved method for large-scale preparation of cinnamomin and camphorin from
      the seeds of Cinnamomum camphora has been developed. Cinnamomin is a type II
      ribosome-inactivating protein (RIP), while camphorin is a type I RIP. Cinnamomin
      was purified by a single step of acid-treated Sepharose 4B affinity
      chromatography instead of gel filtration. Camphorin was purified by anion
      exchange chromatography and gel filtration successively from the eluant not
      retained by the affinity column. Using this improved method, 620 mg of cinnamomin
      and 14.2 mg of camphorin were obtained from 500 g of wet seed, while only 10.6 mg
      of cinnamomin and 4.7 mg of camphorin were obtained by the previous method.
      Cinnamomin and camphorin purified by this method were homogeneous in SDS
      denatured polyacrylamide gel electrophoresis. These two RIPs are multifunctional
      proteins. The assay of the enzymatic activities of cinnamomin and camphorin
      showed that both of them exhibit RNA N-glycosidase and supercoil-dependent
      endonuclease activities, while camphorin also exhibits superoxide dismutase
      activity.

PMID- 9179285
TI  - Purification and characterization of human and mouse recombinant alpha
      fetoproteins expressed in Escherichia coli.
AB  - Alpha-fetoprotein (AFP) is a tumor-associated embryonic molecule whose precise
      biological function(s) remains unclear. A more complete analysis of the
      physiological activities of this oncofetal protein has, until now, been severely
      limited by the lack of an appropriate source from which to obtain pure AFP in any
      sizeable quantity. In the present investigation, we obviate this problem by
      cloning and efficiently overexpressing mature mouse and human AFP cDNA's in
      Escherichia coli. For recombinant mouse AFP (rMoAFP), large segments of the
      coding region were excised from the preexisting plasmids pAFP1 and pAFP2, which
      together encompass 90% of the AFP sequence. The mouse cDNA was made complete by
      the addition of N- and C-terminal encoding oligonucleotides. Mouse AFP cDNA was
      expressed directly as a full-length molecule in vector pTrp4 or as fusion
      proteins in plasmids pMALc and pRX1 under the transcriptional control of trp or
      tac promoters. Accumulation of rMoAFP was significantly increased in protease
      deficient E. coli strains over nonprotease-deficient strains, > or = 10% of total
      cell protein. Of the gene fusion proteins examined, none offered significant
      advantage over the direct expression product in terms of recombinant protein
      stability, overall levels of synthesis, or facilitated purification. Recombinant
      AFP polypeptides expressed by pTrp4 were as expected, deposited in bacterial
      inclusion bodies. Subsequent to resolubilization/refolding, rMoAFP was first
      enriched by passage over Q-Sepharose resin followed by final purification using
      immobilized copper-chelate affinity chromatography. Protein sequencing of the N
      terminus revealed that purified rMoAFP had a deletion of the first nine amino
      acids coded for by the full-length mouse AFP cDNA. Similar N-terminal deletions
      are observed with AFP isolates originating from natural sources. A complete human
      AFP cDNA was generated from a fetal liver cDNA library and was cloned into vector
      pTrp4. Recombinant human AFP (rHuAFP) was expressed under the identical
      conditions employed for rMoAFP but purification had to be modified to include
      preparative Mono Q anion exchange chromatography. N-terminal sequencing, amino
      acid compositional analysis, and electrospray mass spectrometry revealed that
      purified rHuAFP was intact and unaltered and that the initiator methionine was
      completely removed. The biological activity of recombinant AFP, as judged by its
      inhibitory effects on in vitro lymphocyte proliferation, was equivalent to that
      of the native protein. The availability of large quantities of mouse and human
      recombinant AFP molecules should now permit detailed structure-function analyses
      of this important oncofetal protein to proceed in a manner unimpeded by previous
      limitations in both quantity and quality of the native proteins.

PMID- 9179288
TI  - Purification of recombinant lecithin: cholesterol acyltransferase.
AB  - Production and purification of recombinant human lecithin:cholesterol
      acyltransferase (LCAT), secreted by baby hamster kidney (BHK) cells, has been
      improved by limiting the harvesting times for the conditioned medium and
      introducing an additional purification step. The recombinant BHK cells were grown
      until nearly confluent on multilayered flasks in a fetal-calf-serum-enriched
      medium. Subsequently, the cells were washed and supplied with serum free medium
      for 24-h periods. The conditioned medium, containing recombinant LCAT, was
      harvested at 24 and 48 h and subjected to chromatography on phenyl-Sepharose and
      ACA-44 agarose to isolate the recombinant enzyme. The second chromatography step
      revealed the presence of a low-molecular-weight contaminant that exhibited a
      carbohydrate/protein composition similar to proteoglycans. The major purified
      component contained LCAT activity and was homogeneous by acrylamide gel
      electrophoresis.

PMID- 9179287
TI  - Purification and characterization of receptors for activated protein kinase C
      from rat hepatocytes.
AB  - It has been proposed that protein kinase C may be targeted to specific locations
      via interactions with anchoring proteins located at various subcellular sites. A
      group of proteins collectively termed RACKs (Receptors for Activated C-Kinase)
      have been identified. Here, we made use of a rapid and simple method to purify
      several RACKs from rat hepatocytes, taking advantage of the ability of these
      proteins to be precipitated with Triton X-100. The method can be used for the
      isolation of other proteins that share these properties. Four proteins were
      purified to apparent homogeneity with M(r) values of 14, 15, 16, and 34 kDa.
      Amino acid composition and biochemical characteristics of these proteins are
      presented.

PMID- 9179289
TI  - Large-scale isolation of proteins of the large subunit from Escherichia coli
      ribosomes.
AB  - A strategy has been developed and optimized that allows the isolation of proteins
      of the large subunit from Escherichia coli ribosomes and combines the following
      advantages: speed, applicability for the isolation of milligram amounts of a
      single protein, and preservation of the biological activity of the proteins. The
      method consists of the following steps: ion-exchange chromatography on MonoS and
      MonoQ, gel filtration on Sephadex 75, and salt washes. Eleven proteins can be
      purified by a single chromatographic step, and a combination of two steps enables
      the isolation of the other proteins.

PMID- 9179290
TI  - Expression, purification, and characterization of the recombinant NAD-malic
      enzyme from Ascaris suum.
AB  - The cDNA encoding the 65-kDa subunit of malic enzyme from Ascaris suum was cloned
      into the bacterial expression vector pKK223-3 and overproduced in Escherichia
      coli. A protein with a subunit molecular mass of 65,000 was expressed at a level
      of up to 3% of the total soluble protein in JM109, as judged by SDS-PAGE. The
      enzyme was purified using column chromatography on phenyl-Sepharose followed by
      orange-A agarose. The purification procedure resulted in a 32-fold purification
      with an overall yield of 51%. The bacterially expressed enzyme exhibits kinetic
      constants identical to those measured for native A. suum NAD-malic enzyme.

PMID- 9179291
TI  - Lipopolysaccharide binding protein from normal human plasma purified with high
      efficiency.
AB  - Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase plasma
      glycoprotein of 60 kDa which functions as an opsonin on activation of macrophages
      by bacterial LPS. The importance of LBP on the host defense against infection has
      been demonstrated. Human LBP has been purified from ascitic fluid or acute-phase
      serum. However, clinical samples often are not available, so we developed a
      method to purify LBP from normal plasma. The purification was accomplished by
      barium citrate precipitation, followed by three-step ion-exchange chromatography.
      The final step was Mono S cation-exchange chromatography, following Bio-Rex 70
      and Mono Q chromatography, and it enabled the specific activity to increase
      overall 48,000-fold. This seems to be the first report of the use of Mono S
      column to purify LBP. The LBP obtained using these steps proved to be homogeneous
      by SDS-PAGE, Western blotting, and N-terminal sequence and amino acid composition
      analyses. The purification method established here will compensate when normal
      plasma with a low LBP content is available as the starting source.

PMID- 9179292
TI  - Functional expression of bovine opsin in the methylotrophic yeast Pichia
      pastoris.
AB  - The methylotrophic yeast Pichia pastoris was examined for functional expression
      of bovine opsin. An expression plasmid was constructed where the bovine opsin
      gene was placed downstream from the P. pastoris alcohol oxidase 1 gene promoter
      and fused at its amino-terminus to the acid phosphatase secretion signal.
      Quantitative-competitive PCR analysis of a stable yeast transformant showed that
      one copy of the opsin gene was integrated into the yeast genome. The expression
      level in this transformant corresponded to approximately 0.3 mg of opsin per
      liter of cell culture (A600 = 1.0). Sucrose density sedimentation analysis
      indicated that the opsin was associated exclusively with the membrane fraction.
      Similar to retinal opsin, P. pastoris-expressed opsin migrated as a single band
      of approximately 37 kDa on SDS-PAGE and showed high mannose N-glycosylation. A
      portion of the expressed opsin (approximately 4-15%) reacted with 11-cis-retinal
      to form the rhodopsin chromophore (lambda max 500 nm), and after purification
      showed ground and excited state spectral characteristics indistinguishable from
      those of the native pigment. Further, the metarhodopsin-II-mediated G-protein
      activating potential of yeast expressed rhodopsin was similar to that of native
      rhodopsin. These results show that P. pastoris cells have the capacity to
      functionally express bovine opsin.

PMID- 9179293
TI  - Expression in Pichia pastoris and purification of Aspergillus awamori
      glucoamylase catalytic domain.
AB  - In this paper we report the expression in Pichia pastoris, purification, and
      characterization of the Aspergillus awamori glucoamylase catalytical domain
      (GAc). Pichia pastoris produced GAc to the level of 0.4 g per liter medium. This
      production level is about the same level as that gained for recombinant GA from
      Aspergillus and about 100-fold more than previously achieved by Saccharomyces
      cerevisiae. The GAc expressed in Pichia pastoris was purified by two independent
      chromatographic methods employing ion exchange or affinity chromatography to
      apparent homogeneity. The purified protein has a molecular weight of about 75,000
      and specific activity of 78 units per milligram protein. The propeptide present
      in the glucoamylase N terminus was found to be removed correctly by P. pastoris.
      Glucoamylase produced by P. pastoris is N- and O-glycosylated, with 23%
      carbohydrate content. The N-linked oligosaccharides appear to be larger than in
      invertase, another glycoprotein heterologously expressed in P. pastoris. O
      glycosides (studied to our knowledge for the first time in P. pastoris in this
      report) contribute about half of the total carbohydrate content in GAc. Purified
      GAc appears as multiple hands on isoelectric focusing with p1 values around 3.5,
      a value that is little higher than that for GAc produced in S. cerevisiae. GAc
      could be used as a versatile tool in studying protein expression in P. pastoris:
      as an affinity handle for other secreted proteins produced in P. pastoris, as a
      reporter gene when studying gene expression, and as a model protein in studying
      protein secretion and processing in P. pastoris.

PMID- 9179294
TI  - High-level expression of the prohormones proenkephalin, pro-neuropeptide Y,
      proopiomelanocortin, and beta-protachykinin for in vitro prohormone processing.
AB  - Prohormone substrates are required for investigation of the proteolytic
      processing of prohormones and proproteins into active peptide hormones and
      neurotransmitters. However, the lack of prohormone proteins has been a limiting
      factor in elucidating proteolytic mechanisms for conversion of prohormones into
      active peptides. Therefore, in this study, cloned cDNAs encoding the prohormones
      proenkephalin (PE), pro-neuropeptide Y (pro-NPY), pro-opiomelanocortin (POMC),
      and beta-protachykinin (beta-PT) were utilized to express recombinant prohormones
      in Escherichia coli. High-level expression of milligrams of prohormones was
      achieved with the pET3c expression vector utilizing the T7 promoter for
      production of PE, pro-NPY, and POMC, as demonstrated by SDS-PAGE gel
      electrophoresis, Western blots, and 35S-methionine labeling. In addition, beta-PT
      was expressed at high levels as fusion proteins with the maltose-binding protein
      and glutathione S-transferase by the pMAL-c and pGEX-2T expression vectors,
      respectively. Relative rates of processing by the established processing
      proteases "prohormone thiol protease" (PTP), 70-kDa aspartyl protease, and PC1/ 3
      and PC2 (PC, prohormone convertase) were examined with purified PE, pro-NPY, and
      POMC. Distinct preferences of processing enzymes for different prohormones was
      demonstrated. PTP preferred PE and pro-NPY substrates, whereas little processing
      of POMC was detected. In contrast, the 70-kDa aspartyl protease cleaved POMC more
      readily than pro-NPY or PE. However, PC1/3 and PC2 prefer POMC as substrate.
      Demonstration of selectivity of processing enzymes for prohormone substrates
      illustrates the importance of expressing recombinant prohormones for in vitro
      processing studies.

PMID- 9179295
TI  - Rat dihydroorotate dehydrogenase: isolation of the recombinant enzyme from
      mitochondria of insect cells.
AB  - Mammalian dihydroorotate dehydrogenase (EC 1.3.99.11), the fourth enzyme of
      pyrimidine de novo synthesis is located in the mitochondrial inner membrane with
      functional connection to the respiratory chain. From the cDNA of rat liver
      dihydroorotate dehydrogenase cloned in our laboratory the first complete sequence
      of a mammalian enzyme was deduced. Two hydrophobic stretches centered around
      residues 20 and 357, respectively, and a short N-terminal mitochondrial targeting
      sequence of 10 amino acids was proposed. A recombinant baculovirus containing the
      rat liver cDNA for dihydroorotate dehydrogenase was constructed and used for
      virus infection and protein expression in Trichoplusia ni cells. The targeting of
      the recombinant protein to mitochondria of the insect cells was monitored by
      activity determination of dihydroorotate dehydrogenase in subcellular
      compartments in comparison to succinate dehydrogenase activity (EC 1.3.5.1),
      which is a specific marker enzyme of the inner mitochondrial membrane. The
      results of subcellular distribution were verified by Western blotting with anti
      dihydroorotate dehydrogenase immunoglobulins. The activity of the recombinant
      enzyme in the mitochondria of infected insect cells was found to be about 570
      fold above the level of dihydroorotate dehydrogenase in rat liver mitochondria.
      By cation exchange chromatography of the Triton X-114 solubilisate of
      mitochondria, dihydroorotate dehydrogenase was purified to give a specific
      activity of 15 U/mg at pH 8.0. This was a marked progress over the six-step
      purification procedure of the enzyme from rat liver which resulted in a specific
      activity of 0.7 U/mg at pH 8.0. The characteristic flavin absorption spectrum
      obtained with the recombinant enzyme gave strong evidence that the rodent enzyme
      is a flavoprotein. By enzyme kinetic studies K(m) values for dihydroorotate and
      ubiquinone were 6.4 and 9.9 microM with the recombinant enzyme, and were 5.0 and
      19.7 microM, respectively, with the rat liver enzyme. After expression of only
      truncated forms of human dihydroorotate dehydrogenase, the present successful
      generation of the complete rodent enzyme using insect cells and the efficient
      procedure will promote structure and function studies of the eukaryotic
      dihydroorotate dehydrogenases in comparison to the microbial enzyme.

PMID- 9179296
TI  - cDNA cloning, expression, and rapid purification of a Kunitz-type winged bean
      chymotrypsin inhibitor.
AB  - A 183-residue Kunitz-type winged bean chymotrypsin inhibitor (WbCI), inhibits its
      cognate protease at a molar ratio of 1:2, instead of the usual ratio of 1:1
      common to other members of the family. From the cDNA pool obtained by reverse
      transcription of the poly(A)+ RNA of the developing winged bean seeds, the
      structural gene of WbCI has been amplified by PCR using primers designed to
      delete the 24-residue signal peptide and introduce EcoRI and SalI sites at the
      ends of the amplified DNA. The latter is cloned in pBluescript and the insert has
      been sequenced to confirm its authenticity. Subcloning it in pTrc99A, a high
      expression vector for Escherichia coli has generated a chimeric plasmid, pTrc
      WbCI, which has a reading frame for a recombinant protein (rWbCI), having an
      additional tripeptide (M-E-F) fused to the N-terminus of WbCI. The expression of
      rWbCI has been ascertained by immunoblot analysis using rabbit anti-WbCI immune
      sera and quantitated by ELISA. The optimal conditions for the induction of the
      protein by IPTG, avoiding complications of protein-body formation, have also been
      standardized. rWbCI has been purified by a simple and rapid procedure of
      immunoaffinity chromatography, with an overall yield of 1.3 mg/g wet cell. SDS
      PAGE analysis shows the presence of a single protein band, attesting to the
      homogeneity of the preparation; functionally, it is indistinguishable from WbCI
      since they inhibit alpha-chymotrypsin in an identical manner.

PMID- 9179297
TI  - Recombinant expression and secretion of a natural splicing variant containing the
      ectodomain of porcine LH receptor in HC11 mammary epithelial cells.
AB  - Large-scale synthesis of active recombinant porcine luteinizing hormone/chorionic
      gonadotropin receptor (pLHR) is required for biophysical and structural studies.
      This study was undertaken to improve expression of the corresponding cDNA already
      obtained with a number of other systems, (i) by turning to cells from mammalian
      origin able to perform adequate glycosylation, (ii) by using an expression vector
      containing the acknowledged high-performance rabbit WAP gene upstream region
      together with transcription and translation stimulating sequences, and (iii) by
      expressing natural splicing variants. Selection of the transfected HC11 cells was
      performed in terms of pLHR expression using specific radioligand binding and
      immunoradiometric assays. Secretion of pLHR ectodomain into the culture medium of
      the HC11 clones was quantified, and reached 70 ng/ml, which represents the
      highest active amount ever produced. However, this level of expression was
      relatively low in comparison to that currently observed with bGH cDNA used as
      reporter gene. Additional investigations were performed in order to gain further
      insight into the limitation of the production of pLHR relative to bovine or human
      growth hormone using the same expression system. A high number of copies of cDNA
      in the genome of HC11 cells was found, provided that an antibiotic selection
      pressure was maintained to avoid drifting. The low mRNA levels detected for pLHR
      relative to hGH mRNAs correlate well with the relative protein production levels.
      They could arise from poor stability of mRNAs, a fact already observed for the
      natural receptor in gonadal cells. These results thus constitute a promising
      indicator for possible expression of pLHR in the milk of transgenic animals.

PMID- 9179298
TI  - Bacterial expression of human vitamin D-binding protein (Gc2) in functional form.
AB  - In this report, we report the first expression of human vitamin D-binding protein
      (hDBP), a serum protein with several functions and a multidomained structure, in
      Escherichia coli. The recombinant protein (reDBP) was expressed as a fusion
      partner of glutathione S-transferase in order to facilitate proper folding of the
      reDBP; E. coli-expressed DBP was found to be fully functional with respect to
      vitamin D sterol binding, interaction with actin, and cross-reactivity with anti
      DBP antibody. Furthermore, both natural DBP and reDBP were affinity-labeled with
      25-hydroxyvitamin D3-3-bromo[1-14C]acetate in a similar fashion. Availability of
      an expression system for hDBP in functional form provides opportunity to develop
      mutants and truncated DBPs to study multiple ligand-binding properties of this
      protein in relationship with its structure.

PMID- 9179299
TI  - In vitro folding and functional analysis of an anti-insect selective scorpion
      depressant neurotoxin produced in Escherichia coli.
AB  - The selective toxicity of depressant scorpion neurotoxins to insects is useful in
      studying insect sodium channel gating and has an applied potential. In order to
      establish a genetic system enabling a structure-activity approach, the functional
      expression of such polypeptides is required. By engineering the cDNA encoding the
      depressant scorpion neurotoxin, LahIT2, behind the T7 promoter, large amounts of
      recombinant insoluble and nonactive toxin were obtained in Escherichia coli.
      Following denaturation and reduction, the recombinant protein, constructed with
      an additional N-terminal methionine residue, was subjected to renaturation.
      Optimal conditions for reconstitution of a functional toxin, having a dominant
      fold over many other possible isoforms, were established. The recombinant active
      toxin was purified by RP-HPLC and characterized. Toxicity (ED50) to insects,
      binding affinity (IC50) to an insect receptor site, and electrophysiological
      effect on an insect axonal preparation were found to be similar to those of the
      native toxin. Substitution of the C-terminal glycine by a Gly-Lys-Lys triplet did
      not abolish folding but affected toxicity (3.5-fold decrease) of LqhIT2.
      Apparently, this efficient bacterial expression system (500 micrograms HPLC
      purified toxin/1 liter E. coli culture) provides the means for studying
      structure/ activity relationship and the molecular basis for the phylogenetic
      selectivity of scorpion depressant neurotoxins.

PMID- 9179300
TI  - Yeast chromatin reconstitution system using purified yeast core histones and
      yeast nucleosome assembly protein-1.
AB  - Transcription regulation in the cell occurs in the context of chromatin. It
      follows that a thorough investigation of the mechanism of transcription
      regulation must take into account the role of chromatin structure. Through
      classical and molecular genetic experiments in yeast, great strides have been
      made in understanding the role of chromatin in eukaryotic gene regulation. To
      achieve a more detailed understanding of the biochemical mechanism of
      transcription regulation, a yeast chromatin reconstitution system is needed. This
      need drove us to develop a yeast core histone purification procedure for the
      reconstitution of these histones into chromatin templates using components wholly
      derived from yeast. We have purified native yeast core histones in milligram
      quantities and we have shown these histones to be competent for reconstitution of
      chromatin templates using yeast nucleosome assembly protein-1. This
      accomplishment sets the stage for studies using the full power of yeast as an
      experimental organism to investigate the role of chromatin in transcription
      regulation.

PMID- 9179301
TI  - Overexpression and large-scale purification of recombinant hamster polymorphic
      arylamine N-acetyltransferase as a dihydrofolate reductase fusion protein.
AB  - N-Acetyltransferases (NATs) are enzymes that catalyze the detoxification and/or
      bioactivation of a variety of xenobiotics. Rapid kinetic, biophysical,
      structural, and bioactivation studies on NATs require quantities of purified
      enzyme capable of being obtained only through recombinant DNA technology. This
      laboratory has previously developed a protein expression and purification system
      in which NATs are expressed as proteins fused to a FLAG octapeptide followed by a
      thrombin-cleavage site to allow liberation of the rNAT. Typically, however, only
      0.5-1.5 mg of the recombinant NAT's could be readily purified in a single
      isolation sequence by immunoaffinity chromatography. Therefore, the expression
      system was modified by inserting the L54F dihydrofolate reductase (DHFR) mutant
      gene sequence between the FLAG octapeptide and the thrombin-cleavage site.
      Expression was carried out with TOPP3 Escherichia coli cells. The new
      purification methodology utilizes the unique pH dependence of binding to a
      methotrexate (MTX)-affinity column by the L54F DHFR mutant. Unfortunately, the
      affinity chromatography strategy did not work satisfactorily. Although the
      specific activity of the purified rNAT2 was comparable to that of NAT2 obtained
      from hamster tissue, only 3% of the activity was recovered. The apparent cause of
      the low recovery is the unanticipated irreversible binding of rNAT2 to MTX. Ion
      exchange chromatography was investigated as an alternative purification method.
      An initial DEAE anion-exchange column resulted in partial purification of the
      fusion protein. The fusion protein was cleaved with thrombin and reapplied to a
      DEAE anion-exchange column. The second DEAE column resulted in not only the
      separation of rNAT2-70D from FLAG-L54F DHFR, but also the purification of rNAT2
      70D to near homogeneity. Application of the nearly homogeneous rNAT2-70D to a gel
      filtration column resulted in recovery of homogeneous protein. The ion-exchange
      method of purifying rNAT2-70D is inexpensive and simple and yields more than 8 mg
      of pure enzyme from 1 liter of cell culture.

PMID- 9179302
TI  - Recombinant human 92-kDa type IV collagenase/gelatinase from baculovirus-infected
      insect cells: expression, purification, and characterization.
AB  - Human 92-kDa type IV collagenase/gelatinase (MMP9) has been expressed in insect
      cells and secreted into the cell medium via a baculovirus expression system. The
      expression level of the proenzyme from Trichoplusia ni cells was estimated to be
      > = 300 mg/L of cell medium. The recombinant protein was purified in a single
      step using heparin-affinity chromatography with an overall yield of ca. 70%. The
      purified zymogen could be activated in vitro using 4-aminophenylmercuric acetate
      to yield an active protease. Kinetic analysis of the activated recombinant enzyme
      demonstrates that this material is comparable to activated MMP9 from natural
      human sources. The recombinant enzyme provides a useful source of protein for a
      variety of biochemical and biophysical studies aimed at elucidating the structure
      and function of human MMP9.

PMID- 9179303
TI  - Improved membrane isolation in the purification of beta 2-adrenoceptors from
      transgenic Escherichia coli.
AB  - beta 2-Adrenoceptors (beta 2-AR) have been purified from many mammalian tissues.
      Unfortunately, other beta-AR subtypes expressed in the same cells are usually
      copurified, contaminating the preparation and interfering with subsequent
      investigations such as receptor characterization, ligand binding studies,
      immunoprecipitation, or development of anti-receptor antibodies. The advent of
      molecular biology techniques has facilitated the expression of beta 2-AR in cells
      in which no other similar molecules are present; thus, receptor purification has
      been simplified. beta 2-AR expressed in Escherichia coli provides a convenient
      source of receptor without the need for specialized culture facilities required
      for eukaryotic cells. The greater complexity of the gram-negative cell wall
      structure, however, complicates the purification of membrane-bound receptor from
      this source. In this report, we describe a reliable method for the partial
      purification of membrane-bound beta 2-AR from transgenic E. coli. Spheroplast
      formation followed by cell disruption and a carbonate wash procedure provided
      beta 2-AR bound to bacterial inner membrane in high yield.

PMID- 9179304
TI  - Effect of atrial natriuretic factor and fate of cyclic-guanosine-monophosphate in
      the rat kidney.
AB  - The mechanisms whereby atrial natriuretic factor (ANF) induces natriuresis are
      not clarified. Here, the effects of ANF and the cGMP analogue, 8-bromo-cGMP, on
      Na+, K(+)-ATPase activity in microdissected segments from rat medullary thick
      ascending limb of Henle (TAL) were evaluated. ANF-induced cGMP accumulation and
      the cellular handling of intracellularly produced cGMP were also investigated, by
      measuring the accumulation of extracellular cGMP in suspensions of tubules from
      outer medulla, enriched in TAL, and of isolated glomeruli. ANF dose-dependently
      inhibited Na+, K(+)-ATPase activity in isolated TAL in a parallel fashion with
      increasing cGMP accumulation in OM tubules. For both parameters, pharmacological
      concentrations (> or = 10(-6) M) of ANF were needed to induce a significant
      effect. 8-Bromo-cGMP mimicked the inhibitory effect of ANF. The increase in the
      intracellular cGMP level in response to ANF was dose-dependently reflected in the
      extracellular level. This finding contrasted with that in the glomerular
      preparation, where cGMP in response to ANF accumulated entirely intracellularly.
      Also in glomeruli, high (> or = 10(-6) M) concentrations of ANF were needed to
      induce a significant effect on cGMP accumulation. In conclusion, ANF inhibited
      Na+, K(+)-ATPase activity in TAL and the effect was mimicked by 8-bromo-cGMP.
      cGMP, produced in response to ANF, was extruded from the tubular epithelial
      cells, but not from glomeruli.

PMID- 9179305
TI  - The goat mammary gland as a target organ for atrial natriuretic peptide.
AB  - Milk secretion represents a major route for electrolyte and water excretion in
      the dairy goat. The aims of this study were to investigate whether the mammary
      gland is a target site for atrial natriuretic peptide (ANP) in the goat and
      whether ANP affects mammary sodium and water secretion. Receptor autoradiography
      using 125I-ANP as radioligand revealed specific binding sites in the secretory
      tissue of the mammary gland. The radioligand was totally displaced by unlabelled
      ANP, but not by brain natriuretic peptide or the ANP fragment c-ANP4-23,
      indicative of ANP-A receptor preference. To elucidate the role of ANP in milk
      secretion, ANP (30 ng kg-1 min-1; 120 min) or 0.15 M NaCl (control) were
      administered in vivo. The ANP infusions caused haemoconcentration, but did not
      change milk flow or the concentrations of sodium, potassium, lactose, fat and
      protein in the milk. The results show that the mammary gland of the goat
      expresses ANP-specific binding sites, however, a physiological role of ANP in
      goat mammary gland function remains to be elucidated.

PMID- 9179306
TI  - Pituitary adenylate cyclase activating peptide (PACAP) in salivary glands of the
      rat: origin, and secretory and vascular effects.
AB  - Pituitary adenylate cyclase activating peptide (PACAP)-38, injected i.v. to the
      anaesthetized rat, evoked secretion of saliva from the three major salivary
      glands, the submandibular glands responding with the greatest and the sublingual
      glands with the smallest volumes. The parotid saliva was rich in amylase and
      protein. In vitro, pieces of parotid and submandibular gland tissues released K+
      and protein in response to PACAP-38, with atropine and adrenoceptor antagonists
      present. The blood flow in the submandibular gland increased in response to PACAP
      38, despite a marked fall in mean aortic blood pressure. PACAP is a vasoactive
      intestinal peptide (VIP)-like neuropeptide. A comparison between the two peptides
      showed PACAP-38 to be more effective than VIP with respect to vascular responses
      and less or equi-effective with VIP with respect to the secretory responses, thus
      suggesting the involvement of PACAP type I and type II receptors, respectively
      PACAP-38 and -27 were present in the parotid gland as judged by radioimmunoassay,
      the concentration of the former being about twice that of the latter.
      Parasympathetic denervation, by cutting the auriculo-temporal nerve, reduced the
      total parotid gland contents of PACAP-38 and -27 by 23 and 44%, respectively
      (compared with a previously demonstrated 95% reduction of VIP). Sympathetic
      denervation, section of the facial nerve or treatment with the sensory neurotoxin
      capsaicin did not affect the content of PACAP. The difference in efficacy between
      PACAP and VIP in the vascular and secretory responses as well as the difference
      in localization suggest that the two peptides play different physiological roles
      in the salivary glands.

PMID- 9179307
TI  - Cardiovascular and catecholamine responses to static exercise in partially
      curarized humans.
AB  - Neural control of the circulation was evaluated during static exercise in 19
      subjects by the determination of heart rate (HR), mean arterial pressure (MAP),
      cardiac output (CO) and plasma catecholamines. Influence from central command was
      evaluated during contractions with weakened muscles following partial
      curarization and reflex influence from metaboreceptors was assessed by post
      exercise muscle ischaemia. Static handgrip increased HR and more so MAP and CO
      and MAP remained elevated during post-exercise muscle ischaemia. With partial
      curarization plasma catecholamines were also increased (P < 0.05). Two-leg
      extension increased all variables and during post-exercise muscle ischaemia
      elevations of HR, MAP and CO were maintained (P < 0.05). With partial
      curarization HR, MAP and plasma noradrenaline were even greater during the
      contraction. With the involvement of both legs during static exercise, reflex
      influence from the muscles elevated blood pressure by way of HR and CO and the
      importance of central command was detectable for HR and MAP as plasma
      catecholamines became elevated. However, the results indicate a separation
      between a central command influence on HR and CO related to an increase in plasma
      catecholamines during a handgrip, while the reflex influence on blood pressure
      was directed towards total peripheral resistance.

PMID- 9179308
TI  - Increased finger arterial blood pressure after exercise detraining in women with
      parental hypertension: autonomic tasks.
AB  - The effects of exercise detraining on resting finger arterial blood pressure
      (BP), the carotid-cardiac vagal baroreflex, and BP and heart rate (HR) responses
      to mental arithmetic and forehead cold exposure were studied in young (19 +/- 1.1
      years) normotensive women with parental history of hypertension. Following 8
      weeks of aerobic exercise for 25 min, 3 days week-1 at an intensity of 60%
      VO2peak, subjects ceased training for 6-8 weeks. After detraining, VO2peak (mL kg
      1 min-1) was reduced by 11.5% (41.1 +/- 6.9 to 36.4 +/- 4.8) coincident with an
      approximately equal to 10% increase in submaximal exercise heart rate. Responses
      to the laboratory tasks were then compared. Detraining was accompanied by
      increases (P < 0.05) in resting systolic (SBP) (113.6 +/- 8.9 to 121.2 +/- 9.0),
      diastolic (DBP) (63.0 +/- 8.4 to 68.3 +/- 6.8), and mean arterial (MAP) (78.7 +/-
      8.4 to 84.2 +/- 7.3) BP (mmHg). None of the above changes occurred in sedentary
      matched-control subjects. Systolic blood pressure was elevated during forehead
      cold exposure and MAP was elevated during mental arithmetic after detraining, but
      the rates of response and recovery for SBP, DBP and MAP were not altered by
      detraining. Despite higher submaximal exercise HR after detraining, HR responses
      to autonomic challenges, including the carotid-cardiac vagal baroreflex, were
      unchanged between training and detraining. Our results indicate that exercise
      detraining increases resting finger arterial BP in young normotensive women at
      risk for hypertension with no effects on the rate of response or recovery of
      heart rate and BP during autonomic tasks known to elicit sympathetic and carotid
      cardiac vagal activities in this population. The use of auscultatory brachial
      artery pressures in a similar study of women diagnosed with hypertension will
      clarify the clinical meaning of our findings.

PMID- 9179309
TI  - Middle cerebral artery blood velocity, arterial diameter and muscle sympathetic
      nerve activity during post-exercise muscle ischaemia.
AB  - During exercise the transcranial Doppler determined mean blood velocity (Vmean)
      increases in the middle cerebral artery (MCA) and reflects cerebral flood flow
      when the diameter at the site of investigation remains constant. Sympathetic
      activation could induce MCA vasoconstriction and in turn elevate Vmean at an
      unchanged cerebral blood flow. In 12 volunteers we evaluated whether Vmean
      relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during
      rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter
      of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a
      peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 +/- 20 to
      92 +/- 21 beats min-1 and mean arterial pressure (MAP) from 87 +/- 7 to 105 +/- 9
      mmHg (mean +/- SD; P < 0.05). During PEMI, HR returned to pre-exercise levels
      while MAP remained elevated (101 +/- 9 mmHg). During handgrip contralateral MCA
      Vmean increased from 65 +/- 10 to 75 +/- 13 cm s-1 and this was more than on the
      ipsilateral side (from 63 +/- 10 to 68 +/- 10 cm s-1; P < 0.05). On both sides of
      the brain Vmean returned to baseline during PEMI. MSNA did not increase
      significantly during handgrip (from 56 +/- 24 to 116 +/- 39 units) but the
      elevation became statistically significant during PEMI (135 +/- 86 units, P <
      0.05), while AD did not change. Taken together, during exercise and PEMI, Vmean
      changed independent of an elevation of MSNA by more than 140% and the dorsalis
      pedis artery diameter was stable. The results provide no evidence for a
      vasoconstrictive influence of sympathetic nerve activity on medium size arteries
      of the limbs and the brain during rhythmic handgrip and post-exercise muscle
      ischaemia.

PMID- 9179310
TI  - High proportion of type I fibres in thigh muscle of young dancers.
AB  - A previous study showed that adult female dancers have a high percentage of type
      I fibres in vastus lateralis, similar to that of endurance-trained female runners
      or female cross-country skiers. It is not known if dancers already at an early
      age are characterized by a high percentage of type I fibres or develop a high
      percentage of type I fibres as a consequence of dance training. Furthermore, the
      muscle fibre composition of male dancers has not previously been studied.
      Therefore the aim of the study was to analyse skeletal muscle fibre
      characteristics in 10-year-old and 20-year-old dancers of both sexes. Age-matched
      boys and girls whose physical activity was average for their age groups served as
      controls. Muscle biopsies for histochemical analysis were obtained from vastus
      lateralis using the percutaneous needle technique. The major finding of the
      present study was that the vastus lateralis of young dancers of both sexes had a
      higher percentage of type I fibres than that of controls. Moreover, the higher
      type I percentage was seen not only in 20 year olds, but also in 10 year olds,
      who had begun their dance training at a professional level only a few weeks
      earlier. No significant difference in this respect was found between female and
      male dancers. In conclusion, the muscle fibre type composition in young dancers
      of both sexes differs from that of the average individual of the same age and is
      characterized by a high percentage of type I fibres.

PMID- 9179311
TI  - Cardiovascular regulation by endogenous nitric oxide is essential for survival
      after acute haemorrhage.
AB  - Our previous studies have indicated that endogenous nitric oxide serves as a
      physiologically important inhibitor of vascular tone during acute haemorrhage.
      This vasodilator action attenuates the concomitant reflex adrenergic constriction
      and thereby prevents critical reduction of tissue blood flow. The present study
      aimed to evaluate the overall importance of this nitric oxide regulation for
      survival after acute haemorrhage. This was done by comparative observations of
      survival time and circulatory, metabolic and histopathological changes after an
      acute standardized lethal blood loss (45%) in cats exposed to nitric oxide
      synthase (NOS) inhibition and in matched control animals with intact nitric oxide
      regulation. NOS inhibition was instituted by intravenously administered N omega
      nitro-L-arginine methyl ester. The survival time averaged 2 h 49 min in the NOS
      blocked animals and 10 h 14 min in the control animals (P < 0.001). NOS
      inhibition thus reduced the posthaemorrhagic survival time to < 30% of that in
      the control cats. Haemorrhage in the NOS-blocked animals led to rapidly
      developing arterial hypotension, increased anaerobic metabolism, metabolic
      lactacidosis, hyperkalaemia, and morphological tissue damage especially in heart
      and liver, in spite of maintained arterial normoxia, which signifies tissue
      hypoxia caused by seriously impaired nutritional blood supply. At the time of
      death of the NOS-blocked cats, the control animals still exhibited a virtually
      normal circulatory/metabolic state. A much later, and more slowly developing
      circulatory/metabolic deterioration was observed in the control animals. These
      differences between the two groups of animals indicate that nitric oxide release,
      by its vasodilator action, to a significant extent helps to maintain an adequate
      nutritional blood supply to the tissues in acute haemorrhage.

PMID- 9179312
TI  - The capillarity of the subendocardium of left ventricle in rats reared at a low
      temperature for many generations.
AB  - The cardiac capillarity in adult rats reared at 5 degrees C for 68 generations
      was studied with a double staining method of alkaline phosphatase and
      dipeptidylpeptidase IV. Capillary density, proportions of arteriolar,
      intermediate and venular capillary portions and capillary domain area were
      measured in the left ventricular wall. Compared with the control rats which had
      been brought back from the low temperature at the 12th generation and reared at
      25 degrees C since then, the heart and the cardiac cells were hypertrophied,
      total capillary density increased and the capillary domain areas were reduced
      along the capillary path from the arteriolar to venular capillary portions. The
      number of the venular capillary portions showed no significant change but the
      arteriolar and intermediate capillary portions significantly increased. All these
      changes suggest that the cardiac capillary network was better developed in the
      cold-reared rats than in control rats. In the cold-adapted rats the hypertrophic
      changes in cardiac cells are thus accompanied by improvements in the oxygen
      delivery capacity. This adaptation provides a basis for the maintenance of
      increased thermogenesis in many organs. The changes cannot be established by
      several weeks exposure to low temperature, but only after rats have been bred in
      a cold room for generations.

PMID- 9179313
TI  - Glucose metabolism of the inner retina in pigs in darkness and light.
AB  - In the pig eye, oxygen and glucose consumption in the outer retina are reduced in
      light compared to the consumption in the dark and most of the glucose consumed is
      metabolized to lactate both in light and in the dark. In the present study, in
      order to characterize the metabolism of glucose in the inner retina. Blood was
      collected from an artery and from a plexus on the optic nerve draining blood from
      the retina. Arteriovenous concentration differences for glucose, lactate and
      oxygen were determined. Observations were made in dark-adapted eyes and then
      after light adaptation. The consumption of oxygen and glucose and the lactate
      formation in the inner retina were calculated on the basis of these observations
      and recent data for retinal blood flow. In dark-adapted eyes, approx. 69% of the
      glucose was oxidized and approx. 20% was used in lactate formation. After 5-10
      min of exposure to constant light, the levels of oxygen consumption and lactate
      formation were no different from those in darkness. The results indicate that
      lactate formation is a normal property of the pig inner retina, but that it is
      much less pronounced than in the outer part. The metabolism of the inner retina
      in constant light is similar to that in darkness. A comparison with data for the
      outer retina indicates that oxygen consumption in the inner retina in constant
      light is approx. 47% of that in the whole retina, while for glucose consumption
      and lactate production, the corresponding figures are approx. 12 and 8%,
      respectively.

PMID- 9179314
TI  - Glucose metabolism in pig outer retina in light and darkness.
AB  - Glucose metabolism in the outer retina of pigs was studied in the light and in
      the dark in pentobarbital anaesthetized pigs. Blood was collected from a vortex
      vein and an artery, and the arteriovenous concentration differences of lactate,
      glucose and oxygen were determined in light-adapted eyes. Local blood flows were
      simultaneously determined using the microsphere method. In a second group of
      experiments, the flow from a vortex vein and arteriovenous concentration
      differences were measured in both darkness and light. In light, the mean net
      lactate formation and oxygen and glucose consumption in the outer retina were
      about 0.137, 0.150 and0.115 mumol min-1, respectively. In eyes previously dark
      adapted, constant light caused a 63% reduction in lactate formation, whilst
      oxygen and glucose consumptions were reduced by 40 and 44%, respectively. The
      results indicate that in both darkness and constant light, most of the glucose
      consumed by the outer retina is used in lactate formation, and that less than 20%
      is oxidized. Energy production through glycolysis and glucose oxidation is
      approx. 42% lower in constant light than in darkness.

PMID- 9179316
TI  - Pressure-volume relationship for rat dermis: compression studies.
AB  - The relationship between tissue hydrostatic pressure and fluid content is an
      important determinant of the response of the microvascular exchange system to
      perturbations. However, only a limited number of studies relating these
      parameters have been reported. To add to this body of information, fully swollen
      rat dermis in vitro was subjected to successive compressive loads in an apparatus
      in which tissue thickness changes were monitored. At steady-state the mechanical
      load on the tissue was balanced by the interstitial fluid pressure within the
      tissue while the fluid content of the tissue was determined from the unstressed
      tissue fluid content and changes in tissue thickness. The range of conditions
      investigated was from moderate overhydration through normal tissue fluid content
      to significant dehydration. From the relationship between interstitial fluid
      pressure and tissue fluid content (expressed as mass of fluid per mass of fat
      free dry tissue) the tissue compliance was determined. Compliance, defined as the
      rate of change of the tissue fluid content with changes in interstitial pressure,
      increased with tissue hydration. The compliance determined using compressive
      loads and steady-state response of tissue thickness compares favourably with the
      limited amount of information available about this tissue property which is
      critical in the determination of tissue fluid balance. Compliance ranged over one
      order of magnitude for the conditions studied and at normal hydration, tissue
      fluid volume changed by about 6.6% per mmHg in tissue hydrostatic pressure.

PMID- 9179315
TI  - Leptin and thermogenesis in humans.
AB  - We examined changes in serum leptin concentrations and thermogenesis in 12
      healthy men (39 +/- 2 years, BMI 22.8 +/- 0.3 kg m-2) during a 4 h euglycaemic
      hyperinsulinaemia performed on a control day and after a day of competitive
      marathon runs. As compared with the control day, after the marathon, baseline FFA
      concentration (543 +/- 0.73 vs. 955 +/- 96 mumol L-1, P < 0.05), lipid oxidation
      rate (0.8 +/- 0.1 vs. 1.2 +/- 0.1 mg kg-1 min-1, P < 0.01) and energy expenditure
      (5.2 +/- 0.1 vs. 5.5 +/- 0.1 kJ min-1, P < 0.01) were elevated. Baseline serum
      leptin concentrations were similar on the control and postexercise days and
      increased during insulin infusion by 35-45% on both days (P < or = 0.01).
      Baseline serum leptin concentration correlated directly with serum insulin (r =
      0.65, P < 0.05) and cortisol (r = 0.64, P < 0.05), and inversely with serum
      growth hormone concentration (r = -0.66, P < 0.05). In the postexercise study,
      the rise in energy expenditure during insulin clamp correlated with serum leptin
      concentration as determined before (r = 0.61, P < 0.05) or at the end of insulin
      infusion (r = 0.55, P < 0.05). Thus, in healthy individuals with normal body
      weight: (1) hyperinsulinaemia increases serum leptin concentrations; (2) a rise
      in energy expenditure correlates with serum leptin concentration. These data
      suggest that leptin is involved in the regulation of energy expenditure in
      humans.

PMID- 9179318
TI  - Effect of inhibition of pentagastrin-stimulated acid secretion on gastric mucosal
      gland luminal pressure.
AB  - We demonstrated previously that hydrochloric acid secreted from the gastric
      glands traverses the mucus layer in channels above the gland openings. The
      driving force for creation of these channels is most probably the hydrostatic
      pressure generated in the gastric gland lumen during stimulation of acid
      secretion. Here we investigated the effect of total inhibition of acid secretion
      on gland luminal pressure. Glandular pressure was measured in vivo with a
      pressure-sensitive microelectrode technique in Inactin-anaesthetized Sprague
      Dawley or Lewis x DA F1 rats. Glandular pressure was significantly reduced after
      ranitidine inhibition of acid secretion, from 17.2 +/- 2.1 mmHg during
      pentagastrin stimulation to 11.2 +/- 1.2 mmHg. This was also true when
      pentagastrin infusion was continued after inhibition of secretion with
      ranitidine. Omeprazole, however, did not significantly alter gland luminal
      pressure although it totally inhibited acid secretion. With continuation of
      pentagastrin infusion after omeprazole inhibition, glandular pressure increased
      significantly from 17.6 +/- 3.4 to 20.1 +/- 3.3 mmHg. In conclusion, total
      inhibition of acid secretion with ranitidine reduces but does not abolish gland
      luminal pressure. After omeprazole inhibition of acid secretion the gastric gland
      luminal pressure persisted or even increased. Since the volume secretion is lower
      after omeprazole administration than during pentagastrin stimulation, the outflow
      resistance most probably had increased after omeprazole injection. Suggestions
      for increased outflow resistance are narrowing in the upper part of the gland
      lumen by conformational changes of the cells or muscle contractions, and/or an
      increase in mucus secretion or viscosity.

PMID- 9179319
TI  - Oxygen consumption and vital organ masses in young growing quail (Coturnix
      coturnix japonica).

PMID- 9179317
TI  - Enhanced increase of plasma sodium pump inhibitory activity to saline expansion
      in vagosympathectomized and anaesthetized dogs.
AB  - To investigate whether plasma sodium pump inhibitory activity is controlled by
      cardiopulmonary and aortic baroreceptors, mean arterial pressure, right atrial
      pressure, sodium and water balances, plasma renin activity, plasma aldosterone
      concentration and plasma antinatriferic activity (PAA; plasma sodium pump
      inhibitory activity) were determined before, during and after Ringer volume
      expansion (10% of body wt) in anaesthetized dogs. Animals were studied with
      intact reflexes (CTR, n = 7) and after acute cervical bilateral vagosympathetic
      denervation (VGT, n = 8). With the exception of PAA, none of the parameters were
      different between groups before, during or after Ringer volume expansion. The PAA
      (microA cm-2) was similar for both groups before expansion and before either sham
      (CTR) or vagosympathectomy (VGT) was performed (CTR = 3.6 +/- 0.4 vs. VGT = 4.3
      +/- 0.3). Compared to baseline, PAA at the end of the volume expansion phase
      increased in both groups (CTR = 6.1 +/- 0.8, P < 0.05; VGT = 9.1 +/- 0.7, P <
      0.0005); however, this PAA value was significantly greater in the VGT group than
      in the CTR group (P < 0.01). At the end of the post-expansion phase, PAA levels
      returned toward baseline in both groups (CTR = 4.4 +/- 0.5 vs. VGT = 4.8 +/- 0.2;
      n.s. vs. baseline); however, this PAA value in the CTR group was not
      significantly different from its pak value. The present data confirm that PAA is
      increased in response to saline volume expansion, and suggest that PAA synthesis
      and/or release is under inhibitory vagosympathetic control during saline volume
      expansion.

PMID- 9179321
TI  - Parental influence on children's socialization to gender roles.
AB  - In a society rife with gender stereotypes and biases, children regularly learn to
      adopt gender roles which are not always fair to both sexes. As children move
      through childhood and into adolescence, they are exposed to many factors which
      influence their attitudes and behaviors regarding gender roles. These attitudes
      and behaviors are generally learned first in the home and are then reinforced by
      the child's peers, school experience, and television viewing. However, the
      strongest influence on gender role development seems to occur within the family
      setting, with parents passing on, both overtly and covertly, their own beliefs
      about gender. This overview of the impact of parental influence on gender role
      development leads to the suggestion that an androgynous gender role orientation
      may be more beneficial to children than strict adherence to traditional gender
      roles.

PMID- 9179320
TI  - Neuropeptide Y Y1 receptor mechanisms in sympathetic vascular control.
AB  - The Y1 receptor is the predominant vascular NPY receptor subtype in pig hind limb
      and kidney. Thus, vascular responses to exogenous and endogenous NPY were almost
      or totally abolished in the presence of the Y1 receptor antagonist BIBP 3226.
      Furthermore, dose-dependent renal vasoconstriction was evoked by a Y1, but not a
      Y2, receptor agonist, and this could be strongly reduced by the Y1 receptor
      antagonist SR 120107A. Moreover, the expression of Y1 receptors in pig kidney and
      renal artery was indicated by RT-PCR and mRNA for Y1 receptors was detected in
      small intrarenal arteries using in situ hybridization. In contrast, the pig
      spleen contains both Y1 and Y2 receptors. In vivo, both Y1 and Y2 receptor
      agonists evoked dose-dependent splenic vasoconstriction, which was strongly
      reduced and not influenced, respectively, by SR 120107A. Accordingly, RT-PCR
      indicated expression of both Y1 and Y2 receptors in pig spleen. Presence of pig
      splenic Y2, but not Y1, receptors was also demonstrated in autoradiographic and
      membrane receptor binding studies. The presence of Y1 receptors in dog spleen was
      demonstrated in vivo, by RT-PCR, autoradiographic and membrane receptor binding,
      the latter also indicating existence of Y2 receptors. In addition, the Y1
      receptor was also demonstrated in dog kidney in vivo and by RT-PCR. 2.
      Selectivity of SR 120107A for Y1 receptors was demonstrated, as Y1 agonist
      binding in dog spleen was displaced with great affinity, in contrast to Y2
      agonist binding in dog and pig spleen. Furthermore, both SR 120107A and BIBP 3226
      potently displaced tritiated BIBP 3226 binding from Y1 receptors in dog splenic
      membranes. BIBP 3226 exerted potent and dose-dependent antagonistic effects on
      contractions evoked by NPY in guinea-pig caval vein in vitro. The inhibition was
      competitive as the slope of the Schild plot was not significantly different from
      unity. SR 120107A appeared as effective as BIBP 3226 to antagonize NPY-evoked
      contractions in this vessel and neither antagonist affected contractions evoked
      by NA. SR 120107A potently antagonized Y1 receptor mediated vasoconstriction
      evoked in pig kidney and spleen in vivo. In contrast, vasoconstrictor responses
      in vivo mediated via other receptors, including Y2, were not affected. SR 120107A
      was also shown to have a long duration of action in vivo. BIBP 3226 exerted dose
      dependent and equally potent antagonism on vascular responses to exogenous and
      endogenous, neurogenically released, NPY in vivo. The elimination of BIBP 3226
      from plasma fit a two-compartment model, resulting in a half-life of 2 and 20 min
      of the alpha- and beta-phase, respectively. It is concluded that continuous
      infusions of this latter antagonist are preferable to infections during in vivo
      experiments, since non-specific effects can be avoided, and the duration of
      antagonistic action is under better control. 3. This study presents the final
      pharmacological evidence for the involvement of endogenous NPY in sympathetic
      vasoconstriction. It was demonstrated that neurogenically released NPY acting on
      Y1 receptors mediates long-lasting contractions of the guinea-pig vena cava in
      vitro. Thus, both SR 120107A and BIBP 3226 almost abolished the long-lasting
      phase of contraction evoked by high frequency stimulation of perivascular
      sympathetic nerves in this vessel, leaving merely an initial adrenergic peak
      contraction. Enantioselective inhibition of the neurogenically-evoked
      contractions in the caval vein was demonstrated, as BIBP 3435, the S-enantiomer
      of BIBP 3226 and virtually devoid of Y1 receptor affinity, was largely without
      effect. Evidence was also presented for the involvement of endogenous NPY in
      nonadrenergic vasoconstriction in vivo. Thus, SR 120107A abolished the long
      lasting phase of nonadrenergic vasoconstriction evoked in hind limb and nasal
      mucosa upon high frequency stimulation of sympathetic nerves in the reserpine
      treated pig in vivo. (ABSTRACT TRUNCATED)

PMID- 9179322
TI  - Family stress, perception of pregnancy, and age of first menarche among pregnant
      adolescents.
AB  - Family-of-origin stress, age of first menarche, and the perception of pregnancy
      as a life event were examined in 97 pregnant adolescents ages 13 to 18. This
      study investigated whether family-of-origin stress levels were significantly
      related to the pregnant adolescent's perception of her pregnancy as a life event.
      The study also examined whether age of first menarche was related to the
      subject's level of family stress. Family stress levels were assessed through the
      Adolescent-Family Inventory of Life-Events and Changes (A-FILE) developed by
      McCubbin & Thompson (1987). Perception of pregnancy as a life event was measured
      on a Likert scale developed by the researcher. Age of first menarche was obtained
      via self-report. Results indicated high levels of family stress among subjects
      with only a moderate level of impact or stress experienced from the pregnancy. As
      a group, the subjects experienced first menarche between 12 to 13 years of age,
      which is the average age supported by other studies within the United States.

PMID- 9179323
TI  - Language arts achievement level, attitude survey format, and adolescents'
      attitudes towards reading.
AB  - The joint effects of student achievement level and attitude survey format upon
      attitudes toward reading were investigated. Sixth-grade students completed
      reading attitude surveys involving a standard Likert-type format or one involving
      pictures of the comic strip character, Garfield. The survey items were identical
      for both formats; only the presentation format was varied. There was no
      significant main effect on attitude responses due to achievement level, but the
      main effect due to survey format was significant, with the Likert-type format
      producing significantly higher attitude responses than the Garfield format. The
      interaction between achievement level and format also was significant, with above
      average students and average students giving higher attitude responses than did
      below average students when the Garfield format was used. When the Likert-type
      format was used, average students and below average students gave higher attitude
      responses than did above average students. The results imply that attitude
      responses of adolescents can be manipulated by varying the format of the survey.

PMID- 9179324
TI  - A literature-based approach to teaching values to adolescents: does it work?
AB  - Articles advocating the use of literature to accomplish a variety of goals is
      common in journals of educational psychology and social work. However, studies
      validating such an approach are scarce. This study attempts to assess the
      effectiveness of one reading project to teach one specific value. Using an
      experimental design in a 7th grade classroom, the researchers introduced the
      reading project as the independent variable, and measured the dependent variable,
      the value of caring for others, with a series of essays. The results of the
      experiment indicate moderate support for the use of literature-based approach to
      teaching values. Changes from pretest to posttest in two of the three essays were
      in the hypothesized direction, However, the authors advise practitioners that the
      use of one discrete project cannot produce large-scale or long-term change.

PMID- 9179325
TI  - Late adolescents' perceptions of their caregiver's feeding styles and practices
      and those they will use with their own children.
AB  - The purpose of this study was to examine the perceptions of late adolescents
      regarding their caregivers' feeding styles and practices and their perceptions of
      those they plan to use with their children. The 546 subjects were from a randomly
      selected sample of 1,000, nonparenting, 18 to 23-year old college students who
      responded to a questionnaire. Two distinct feeding styles emerged: adult
      controlled and cooperative. The adult-controlled style reflects a perception of
      control which the adult decides what and how much a child will eat. The
      cooperative style reflects shared control where the adult decides what food will
      be presented and the child decides how much and whether to eat. Chi-square
      analysis of the relationship between subjects' perceptions of their caregivers'
      feeding styles and their perceptions of the styles they believe they will use
      with their children, resulted in a positive association. To examine perceived
      past and future feeding practices, a Pearson's r was computed on subscales from a
      factor analysis. Results indicated positive correlations between subjects'
      perceived past and future feeding practices. These results suggest generational
      transmission of feeding styles and practices. A recommendation is made for parent
      and nutrition educators to focus on both parenting styles and feeding practices.

PMID- 9179326
TI  - Agency, communion, and achievement motivation.
AB  - This study examined the relationship among (1) two aspects of college students'
      self-concept--the degree to which they reported an agentic or communion
      orientation, (2) two views of intelligence they might hold--entity and
      incremental, and (3) students' tendencies to report adopting attitudes and
      behaviors consistent with a mastery or learned-helpless orientation. Results from
      a survey of a sample of 306 Introductory Psychology students indicate that: (1)
      an incremental view of intelligence was associated with the adoption of mastery
      oriented achievement attitudes and behaviors, while an entity view of
      intelligence was associated with the adoption of learned-helpless attitudes and
      behaviors; (2) both agentic and communion orientations were associated with a
      mastery orientation; (3) an agentic orientation was also associated with lower
      levels of learned-helpless attitudes and behaviors while a communion orientation
      was associated with higher levels of learned-helpless attitudes and behaviors;
      and (4) patterns in the correlation between agency and communion, on the one
      hand, and several indices of students' self-confidence in academic arenas, on the
      other, further supported this asymmetry in the role agency and communion
      orientations appear to play in determining college students' adjustment to
      academic challenges.

PMID- 9179327
TI  - Adolescents and adults at the mall: dyadic interactions.
AB  - The purpose of this descriptive study is to examine differences in interpersonal
      engagements between teen-teen dyads and teen-adults dyads in a mall setting. It
      was expected that behavioral patterns between teen-teen and teen-adult dyads
      would differ as a function of age, gender, and racial composition. Participants
      included 865 teen-teen dyads and 190 teen-adult dyads. Observations were
      conducted in a large mall over four weeks. Observers recorded behavioral
      activity, physical proximity/position, emotional expression, conversation, and
      evidence of shopping. Teen-teen dyads differed from teen-adult dyads on two
      variables, conversation and shopping evidence. Within teen-teen dyad comparisons
      yielded several gender and racial differences, but only one age difference.
      Implications of these findings are discussed.

PMID- 9179328
TI  - The nature and amount of support college-age adolescents request and receive from
      parents.
AB  - While older adolescents appear to spend less time with their families, some
      research has shown parents to be the preferred source of support. The purpose of
      this study is to determine if adolescents receive instrumental and emotional
      support as requested from each parent, and if the support they receive is
      perceived as helpful. Study participants included 206 two-year college students
      (39% males and 61% female) with a mean age of 18.9 years. A mother/father
      adolescent interaction inventory was used to measure perceived parental support
      and the "Who Helps With Your Problems?" inventory was used to measure received
      parental support within a two-week period. Results indicated that adolescents
      received support almost every time it was requested, although few requests were
      made. Gender differences were present for the type of support received, where
      females received significantly more emotional than instrumental support from both
      mothers (t = 3.88, p < .001) and fathers (t = 1.98, p < .05). Additionally, a
      positive correlation was found between perceived and received instrumental and
      emotional support from mothers (r = .33 and r = .27, p < .001 and p < .10,
      respectively) and fathers (r = .33 and r = .37, P < .001), respectively) for
      females only. Possible reasons for gender differences may be due to the roles
      society has ascribed to males and females. Recommendations for future research
      are discussed.

PMID- 9179329
TI  - Economic hardship, family relationships, and adolescent distress: an evaluation
      of a stress-distress mediation model in mother-daughter and mother-son dyads.
AB  - This study evaluated a stress-distress mediation model of the relationships among
      economic hardship, maternal financial strain, maternal marital happiness, the
      parent-child relationships, and adolescent distress in a group of 188 sixth and
      210 eighth graders and their mothers. The model predicted that economic hardship
      would increase maternal financial strain which was predicted to lead to more
      distress in the adolescent children by decreasing the mothers' marital happiness
      and the quality of the mother-child relationship. Separate latent variable path
      analyses with partial least squares (LVPLS) were conducted for the mother
      daughter and the mother-son dyads. The results supported the hypothesized paths
      between economic hardship, mothers' financial strain, the mother-child
      relationship, and adolescent distress in both the mother-daughter and mother-son
      dyads.

PMID- 9179330
TI  - Parricide and violent crimes: a Canadian study.
AB  - Canadian data reveal a positive correlation between the rates for parricide and
      criminal violence from 1962 to 1985. These results run counter to Young's 1993
      results and challenge Megargee's (1982) hypothesis according to which factors
      influencing violent crimes do not similarly affect intrafamilial violence.

PMID- 9179331
TI  - Sexual assault in school, mental health and suicidal behaviors in adolescent
      women in Canada.
AB  - Adolescent women (N = 1,025) in grades 7 through 12 in a stratified random sample
      of Alberta high schools completed measures of emotional problems and suicidal
      behavior in the past six months, and of frequency and type of sexual assault
      (including sexual harassment) experienced in school. It was found that 23% has
      experienced at least one event of assault (sexual touching, sexual threats or
      remarks, or an incident of indecent exposure); 4% had "often" experienced one or
      more of these assaults or harassments. Those experiencing a high number of sexual
      assaults or harassments were significantly more likely to have clinical profiles
      on the measures of emotional disorder; 15% of 38 women experiencing frequent,
      unwanted sexual touching had "often" made suicidal gestures or attempts in the
      previous six months, compared with 2% of 824 women with no experience of sexual
      assault.

PMID- 9179332
TI  - Reliability and validity of Palestinian Student Alienation Scale.
AB  - To develop an a Arabic version of the Student Alienation Scale (SAS), two Arab
      bilinguals achieved consensus in their translation of the twenty-four items. Five
      hundred seventy-four students from 14 to 21 years of age completed the SAS, and
      Beck Depression Inventory (BDI), Satisfaction With Life Scale (SWLS), the Symptom
      Checklist-90-R, and Spheres of Control (SOCQ). Internal consistency was found to
      be high (alpha = .75); split-half reliability was moderately high (.71), and test
      retest was (r = .52, n = 29, p < .01). Estimates of concurrent validity indicated
      a significant correlation between the SAS and BDI, SWLS, SCL-90-R and SOCQ. The
      findings indicated that the Arabic version of SAS is suitable for use in research
      and clinical work.

PMID- 9179333
TI  - A preliminary investigation of high-school counseling resources on the Cape
      Peninsula.
AB  - In South Africa, counseling and guidance services remain marginalized. The aim of
      this study was to determine the structure and function of the counseling
      facilities in high schools on the Cape Peninsula. The first telephone survey
      comprising 68 representatively and randomly selected schools revealed that 26% of
      schools had no guidance department, and the mean full-time guidance teacher-pupil
      ratio was 1:897. The second survey involving 33 randomly selected full-time and
      part-time guidance teachers from the first sample showed that they could assign
      on average 14.4 minutes of counselling per pupil in one school year. Analysis of
      the full-time guidance teachers (N = 22) time allocation revealed that 23% of
      time was allocated to counseling, 32% to guidance, and 45% to formal teaching and
      administration. These results suggest that the allocation of personnel and time
      to counselling are deficient. An implication is that adolescents with
      psychological problems go undetected and therefore untreated.

PMID- 9179334
TI  - Parental bonding and mental health in adolescence.
AB  - Attachment between parent and child plays a crucial role in the healthy
      development of the child. Accordingly disturbances in parental bonding will be
      linked with the development of mental disorders later in life. The present study
      examines the relationship between parental bonding and mental health in healthy
      adolescents. Participants were 847 Israeli high school students who completed the
      Parental Bonding Instrument (PBI), the Brief Symptom Inventory (BSI), the General
      Well-Being (GWB), the Perceived Social Support (PSS), and the Social Desirability
      scale (SDS). In general, Israeli adolescents reported more parental care and less
      control than did Australian adolescents and adults. Female subjects reported more
      maternal care than did males. Subjects who reported high care and low control
      (optimal bonding) reported less distress, better general well-being and better
      social support that did all other groups. In contrast, those who reported low
      care and high control (affectionless control bonding) had the highest BSI scores
      and the lowest GWB and PSS scores. These results are in line with Bowlby's theory
      of attachment. They also show that specific configuration of parental bonding are
      linked with distress and isolation in adolescents.

PMID- 9179335
TI  - Drug use and violent crime among adolescents.
AB  - This study examines the extent to which alcohol and other drug use is related to
      violent and nonviolent criminal activity among adolescents males. Based on data
      collected from 312 youthful offenders at a public juvenile facility, the findings
      reveal that in comparison to marijuana and heroin, alcohol use is more strongly
      and consistently associated with both violent and nonviolent offenses. When other
      factors are introduced into the analysis, the results show that while an
      adolescent's criminal history and racial identity are relatively more important
      in predicting criminal activity overall, the effect of substance use (especially
      alcohol and marijuana) continues to be present.

PMID- 9179336
TI  - Children of alcoholics and adolescence: individuation, development, and family
      systems.
AB  - Recent developmental studies have highlighted the traumatic experiences faced by
      youngsters from alcoholic families. So far, however, the concept of individuation
      has remained missing from the discussion. This article links the developmental
      familial implications of parental alcoholism with the individuation process and
      suggests a developmental agenda for understanding adolescents coping with the
      influences of parental alcoholism.

PMID- 9179337
TI  - Male and female adolescents' perceived interpersonal communication skills
      according to history of sexual coercion.
AB  - This report summarizes the experience of 61 female adolescents recruited through
      a private adolescent family planning clinic, and 183 9th through 12th-grade
      adolescents recruited from a private suburban high school regarding their
      experiences with dating relationships, sexual communication skills, and
      psychological status. The samples were predominantly white and middle to upper
      income. Perceptions of interpersonal communication skills were analyzed according
      to gender, clinic versus school, and history of sexual coercion. The adolescents
      were generally confident that they could assert their own preferences and stand
      up to other regarding sexual issues with the exception of the small group of high
      school males reporting having had experienced sexual coercion. This group (N =
      20) expressed difficulty in talking to their partners about safer sex, getting
      their partner(s) to listen to them, or turning down alcohol or drugs prior to
      having sex. These boys were also more likely to report missing classes or having
      other kinds of trouble with school, to be concerned about use of alcohol and
      drugs, and about feeling unpopular. None of the female groups had this profile of
      communication and emotional problems. Implications for preventive education
      programming on interpersonal skills and sexuality are considered.

PMID- 9179338
TI  - Explorations in a proposed national policy for children and families.
AB  - Empirical evidence suggests that the family system is under pressure in the
      United States. This evidence includes but is not limited to a significant
      increase in out-of-wedlock childbearing by teenagers, an increase in the number
      of children living in families below the poverty level, lack of available health
      care to large numbers of children and families, and a rising number of children
      dropping out of school. The authors offer an analysis of the problems facing
      families, and a national policy model for children and families is proposed.

PMID- 9179339
TI  - Nutrition knowledge among adolescent high school female athletes.
AB  - The purpose of this study is to evaluate the effectiveness of an original sports
      nutrition education program in changing the nutrition behavior of the female high
      school varsity football teams of the Baseline League of Southern California. A
      total of 72 subjects from eight teams were randomly divided into two groups,
      control and experimental. Only the experimental group received nutrition
      education. Dietary habits of the athletes were studied through a pre- and post-
      24-hour recall. A comparison of pretest scores of both groups showed no
      significant difference in level of nutrition knowledge. The posttest scores
      obtained after nutrition education showed a significant difference in nutrition
      knowledge for the experimental group. However, there was no significant
      improvement in dietary intake and food choices due to the limited duration of the
      study.

PMID- 9179340
TI  - Adolescents' attitudes toward the death penalty.
AB  - In this study, a questionnaire was administered to 142 students at two high
      schools (72 boys and 70 girls) and 112 students at a state college (36 men and 76
      women) to determine whether they favored the death penalty for certain criminal
      acts. A questionnaire was also administered to assess extraversion and
      neuroticism. The findings indicated that high school students rated more criminal
      acts as meriting the death penalty than did college students. Gender and
      personality were not found to be associated with attitudes toward the death
      penalty.

PMID- 9179342
TI  - Adolescent females "voice" changes can signal difficulties for teachers and
      administrators.
AB  - This article describes the different preferences in learning styles of adolescent
      females and males, based on the pioneering work on adolescent values development
      by Lawrence Kohlberg and Carol Gilligan. Since values education programs are
      currently considered very important, educators need to explore the philosophical,
      psychological, and social influences on students' learning preferences before
      they can introduce appropriate curricula. An indication of problems in adolescent
      females frequently is the occurrence of voice changes, for example, girls may
      express viewpoints that do not represent their true beliefs and feelings.
      Curricular and co-curricular suggestions are presented.

PMID- 9179341
TI  - Learning disabilities, crime, delinquency, and special education placement.
AB  - This paper explores the influence of learning disabilities on the participation
      of youth in the juvenile justice system. The important role early placement of
      learning disabled youth in public school and in correctional education programs
      is explained and discussed. In addition, social and academic skill remediation is
      suggested as a means of preventing learning disabled youth from dropping out of
      school before incarceration, or of returning to crime upon release from
      incarceration.

PMID- 9179343
TI  - Attachment to parents and peers in late adolescence and their relationship with
      self-image.
AB  - This paper examines older adolescents' (ages 16-18) perceived levels of
      attachment to parents and peers and explores their relationship with self-image.
      Four high school samples were the source of 167 questionnaires. Levels of
      attachment were measured using the Inventory of Parent and Peer Attachment, and
      self-image was assessed using the Offer Self-Image Questionnaire. An ANOVA
      identified significant gender differences, and a multiple regression was used to
      measure the relationship between attachment and self-image. It was found that
      attachment to parents continues to remain strong into late adolescence for males
      and females. Females had significantly stronger attachment to peers. Males had a
      significantly higher level of self-image in a variety of areas of functioning.
      Attachment to parents was found to have a significant relationship with coping
      aspects of self-image, while peer attachment had a strong effect with self-image
      particularly in areas that gain prominence during this developmental period, such
      as body-image, vocational goals, and sexuality attitudes. In examining how
      institutional groups can enhance attachment relationships, it was found that,
      especially among females, groups that stress self-expression and self-discovery
      may enhance attachment relationships and self-image.

PMID- 9179344
TI  - Adolescent gender differences in time alone and time devoted to conversation.
AB  - On the basis of past theory and research, it is hypothesized that adolescent
      females will spend more time in conversation and less time alone than their male
      counterparts. The hypotheses are tested in data from 2,004 seventh and ninth
      grade students in a southeastern metropolitan area. With a number of potentially
      relevant variables taken into account, self-reports of average number of hours
      per week spent alone and spent in conversation are both substantially higher
      among girls than among boys contradicting the time alone hypothesis but
      supporting the conversation time hypothesis and the generalizability of an
      earlier finding of an adolescent gender difference in time spent in conversation.
      The findings are tentatively interpreted in terms of males' orientation toward
      sports, encouraging nonconversation time with others, and females' orientation
      toward close interpersonal relationships, encouraging talk with intimates. In
      additional nonhypothesized findings, black students report significantly more
      conversation time and time alone than do white students.

PMID- 9179345
TI  - FDA approvals include two new AIDS drugs, pediatric labeling for two protease
      inhibitors.

PMID- 9179346
TI  - Pharmacists in patient-focused care.

PMID- 9179347
TI  - The performance of three portable infusion-pump devices set to deliver 2 mL/hr.
AB  - The performance of three portable infusion-pump devices set to deliver 2 mL/hr
      was studied. Portable infusion-pump devices (CADD-1, Paragon, and Singleday
      Infusor) were set to deliver 5% or 25% dextrose in water at 2 mL/hr for 24 hours
      at two environmental temperatures (25 and 35 degrees C). There were a total of 12
      types of experimental runs, and each run was performed in triplicate. Flow rate
      accuracy and flow continuity were measured by a computerized gravimetric
      technique; effusate weights were measured and recorded at 30-second intervals for
      two hours at the beginning and two hours at the end of each run. Mean flow rates
      among the three devices did not differ significantly. Mean flow rate was
      significantly higher for the 5% dextrose solution than for the 25% dextrose
      solution, for the 35 degree C temperature than for the 25 degree C temperature,
      and during the first two hours of delivery than during the last two hours. The
      CADD-1 units showed an interruption of flow lasting about 30 seconds and
      recurring every 60 seconds; the other devices had fairly constant flow. Mean flow
      continuity differed significantly among the three devices. Mean flow continuity
      was significantly higher for the 5% dextrose solution and for the 25 degree C
      temperature. Flow continuity differed among three representative portable
      infusion-pump devices set to deliver 2 mL/hr, but flow rate accuracy did not.
      Fluid viscosity, environmental temperature, and elapsed time affected flow rate
      accuracy and flow continuity.

PMID- 9179348
TI  - Pharmacists on a primary care team at a Veterans Affairs medical center.
AB  - The role of pharmacists on a primary care team in the VA Chicago Health Care
      System--Lakeside Division is described. In 1990 the Veterans Affairs Lakeside
      Medical Center (now called the VA Chicago Health Care System--Lakeside Division)
      implemented the "Firm" system to improve the quality of patient care. This system
      split the original primary care clinics into three identical but smaller groups,
      or Firms. Each Firm provides three types of care: longitudinal care (ongoing care
      with a primary care physician), interim care (frequent care and close patient
      monitoring between primary physician visits), and un-scheduled care (acute care
      for complaints that may require immediate attention). Each Firm has a care team
      composed of physicians, a pharmacist, nurses, and other health care personnel.
      The pharmacist assists with interim care and, in conjunction with Firm
      physicians, is involved in follow-up and monitoring of drug therapy and
      identification of new problems. Originally it was expected that pharmacists would
      care for 30-40% of interim care patients, but Firm pharmacists have assisted in
      providing care to over 50% of these patients (plus 4% of un-scheduled care
      patients). The pharmacists have received high ratings from the internal medicine
      resident staff. Pharmacists on multidisciplinary care teams provided primary care
      to more than half of outpatient veterans in need of health care between regularly
      scheduled appointments.

PMID- 9179349
TI  - Compatibility of propofol injectable emulsion with selected drugs during
      simulated Y-site administration.
AB  - The compatibility of a new formulation of injectable propofol with selected other
      drugs during simulated Y-site injection was studied. Two milliliters of undiluted
      propofol injectable emulsion was combined with 2 mL of each of 112 other drugs in
      5% dextrose injection or 0.9% sodium chloride injection. The liquids were diluted
      with 6 mL of particle-free high-performance liquid chromatography (HPLC)-grade
      water and centrifuged for 20 minutes. A pipette connected to a vacuum line was
      used to remove the fat layer at the top and most of the aqueous phase. The
      remaining liquid was diluted with 9 mL of particle-free HPLC-grade water to
      facilitate visualization of any precipitate. The liquids were examined with the
      unaided eye in fluorescent light and with a Tyndall beam to enhance visualization
      of small particles. Samples were evaluated during the first 15 minutes and one
      hour after mixing. Propofol injectable emulsion was compatible with 98 of the 112
      drugs testes. Fourteen drugs demonstrated incompatibilities, including
      precipitation, gel formation, and oiling out of cracked emulsions. During
      simulated Y-site injection, propofol injectable emulsion was compatible with most
      other drugs tested for one hour at approximately 23 degrees C

PMID- 9179350
TI  - Stability of propafenone hydrochloride in i.v. solutions.
AB  - The stability of propafenone hydrochloride in i.v. solutions was studied.
      Solutions of propafenone hydrochloride 2, 1, and 0.5 mg/mL in 5% dextrose
      injection and in 5% dextrose and 0.2% sodium chloride injection were prepared.
      Portions of each type of solution were transferred to 10-mL polypropylene
      syringes and to 150-mL polyvinyl chloride (PVC) bags. Syringes and bags were
      stored at 20.5-22.5 degrees C under fluorescent light. Two 0.5-mL samples were
      drawn from each container at 0, 6, 12, 24, 36, and 48 hours and frozen in
      polystyrene tubes at -20 degrees C until assayed. Propafenone concentrations were
      determined by high-performance liquid chromatography. All samples of propafenone
      hydrochloride 2 mg/mL in 5% dextrose and 0.2% sodium chloride injection taken
      from PVC bags precipitated when thawed. For the remaining solutions, the mean
      decrease from the initial concentration was < 10% regardless of diluent,
      container type, and initial concentration. Propafenone hydrochloride 1 and 0.5
      mg/mL in 5% dextrose injection or in 5% dextrose and 0.2% sodium chloride
      injection was stable for 48 hours at 20.5-22.5 degrees C when stored in
      polypropylene syringes or PVC bags. Propafenone hydrochloride 2 mg/mL in 5%
      dextrose injection was stable for 48 hours when stored in syringes or bags, but
      in 5% dextrose and 0.2% sodium chloride injection was stable in syringes only.

PMID- 9179351
TI  - Compatibility of parenteral nutrient solutions with selected drugs during
      simulated Y-site administration.
AB  - The compatibility of 102 drugs with parenteral nutrient (PN) solutions during
      simulated Y-site administration was studied. Five milliliters of each of four
      representative PN solutions was combined in duplicate in a 1:1 ratio with 5-mL
      samples of solutions of 102 drugs in 5% dextrose injection or 0.9% sodium
      chloride injection. Visual examinations were performed in fluorescent laboratory
      light and under high-intensity monodirectional light, and turbidity was measured.
      Particle sizing and counting were performed for selected solutions. All
      evaluations were performed at intervals up to four hours; storage was at 23
      degrees C. Most of the drugs tested were compatible with the PN solutions.
      However, 20 drugs exhibited various incompatibilities with one or more of the PN
      solutions. During simulated Y-site administration, four PN solutions were
      compatible with 82 of 102 drugs for four hours at 23 degrees C. Twenty drugs were
      incompatible with one or more of the PN solutions.

PMID- 9179352
TI  - Stability of pentoxifylline in an extemporaneously prepared oral suspension.
AB  - The stability of pentoxifylline in an extemporaneously prepared suspension was
      studied. Twelve 400-mg pentoxifylline tablets were crushed and mixed with water
      to prepare a 20-mg/mL suspension. The suspension was transferred to 10 amber
      glass and 10 amber plastic prescription bottles. Five glass and five plastic
      bottles were stored at 25 degrees C, and the rest were stored at 4 degrees C.
      Samples were collected before storage and on days 7, 14, 21, 28, 42, 56, 70, and
      91 and analyzed in duplicate by stability-indicating reverse-phase high
      performance liquid chromatography. Pentoxifylline was stable in the suspension
      under all storage conditions for the duration of the study. The color, odor, and
      pH of the suspension did not change appreciably. Some settling of the suspension
      was noted in all bottles beginning on day 21, but shaking resuspended the settled
      material. Pentoxifylline 20 mg/mL was stable in an extemporaneously prepared
      suspension for at least 91 days at 25 or 4 degrees C.

PMID- 9179353
TI  - Stability of ranitidine hydrochloride and human insulin in 0.9% sodium chloride
      injection.

PMID- 9179354
TI  - Key factors influencing pharmacists' drug therapy decisions.

PMID- 9179355
TI  - Possible losartan-induced rash.

PMID- 9179356
TI  - E-mail for conducting surveys.

PMID- 9179357
TI  - Multidisciplinary handbook on pediatric nutritional support.

PMID- 9179358
TI  - Mistletoe: a story with an open end.

PMID- 9179359
TI  - Modulation of cytotoxicity and enhancement of cytokine release induced by Viscum
      album L. extracts or mistletoe lectins.
AB  - Cytotoxic effects of Viscum album L. (mistletoe) extracts and mistletoe lectins
      were studied by light and electron microscopy. The first events observed were
      membrane perforation and protrusions typical for apoptosis. Inhibition of Molt 4
      cell growth was obtained with lectin concentrations in the pg/ml range as long as
      cells were cultured in serum-free medium. Under this condition, mistletoe lectin
      III was about 10 times more cytotoxic than mistletoe lectin-I; mistletoe lectin
      II was in between. Lectin cytotoxicity was modulated by human serum from donors
      who had never been treated with mistletoe preparations and lectin-specific
      carbohydrates, added at the mmol/l range, particularly D-galactose (or beta
      lactose) for mistletoe lectin-I and N-acetyl-galactosamine for mistletoe lectin
      II and -III. In addition, at subtoxic concentrations, mistletoe lectin-I, -II and
      -III enhanced the production of cytokines (tumour necrosis factor-alpha,
      interleukin-1 alpha) by isolated human monocytes. The experimental results are
      discussed in relation to the treatment of cancer patients administered with
      mistletoe extracts.

PMID- 9179360
TI  - Differences in the apoptosis-inducing properties of Viscum album L. extracts.
AB  - Viscum album L. (mistletoe) extracts are widely used in adjuvant cancer therapy.
      In contrast to purified components, such as mistletoe lectins and viscotoxins,
      whole plant extracts of mistletoe resulted in DNA stabilizations in
      cyclophosphamide-treated lymphocytes but also provided cytotoxicity in tumour
      cells and lymphocytes. The killing capacities of mistletoe extracts were host
      tree-specific and not correlated with mistletoe lectin or viscotoxin content. In
      human lymphocytes, only mistletoe lectins induced a pathway of apoptotic killing.
      Within 72 h, the lectin B chains also increased the number of lymphocytes
      undergoing apoptosis. This finding suggests that inhibition of protein synthesis
      by the A chain of the hololectin may accelerate a receptor-mediated killing
      pathway induced by the B chains. An unexpected finding was related to the
      mistletoe-mediated killing, which was more effective against CD8+T cells with an
      activated phenotype than CD19+ B cells and CD4+ T cells. In vitro treatment of
      human neutrophils with mistletoe resulted in a slight decrease of phagocytosis
      and burst activity. The observed dose-dependent occurrence of two neutrophil
      subsets with different burst activities indicates differences in their
      susceptibility to mistletoe and suggests the implication of an induction of the
      apoptotic killing pathway.

PMID- 9179361
TI  - Anticarcinogenic and antimetastatic activity of Iscador.
AB  - Methylcholanthrene-induced sarcoma formation in mice was found to be effectively
      inhibited by the intraperitoneal injection of mistletoe extract (Iscador M).
      Induction of sarcoma and sarcoma-induced death were inhibited completely at a
      concentration of 1 mg Iscador/dose. The concentration needed for 50% inhibition
      was found to be 0.0166 mg Iscador/dose. Mistletoe extract was also found to
      inhibit lung metastasis induced by B16F10 melanoma cells in mice. Simultaneous
      administration of the Viscum album extract inhibited lung nodule formation by
      92.0% and produced a 71.3% increase in life span.

PMID- 9179362
TI  - The Viscum album preparation Isorel inhibits the growth of melanoma B16F10 by
      influencing the tumour-host relationship.
AB  - The aim of this study was to analyse whether Viscum album (mistletoe; Isorel)
      modulates the tumour-host relationship and whether this might be a basic
      mechanism of the antitumorous activity of the drug. The effects of a single
      intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were
      analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of
      Isorel reduced the size of the tumour and caused abundant tumour necrosis with
      inflammatory response, oedema and destruction of the malignant tissue.
      Furthermore, the lymphocytes of saline-treated tumorous mice were not able to
      respond to the mitogenic lectin concanavalin A in vitro, while those of mistletoe
      extract-treated mice showed high reactivity too the mitogen, but only if cultured
      in the medium supplemented with the plasma of the mistletoe extract-treated mice.
      Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to
      the cytotoxic activity of the lymphocytes than the control tumour cells,
      particularly in the presence of the plasma of mistletoe extract-treated mice. The
      plasma itself, however, did not show any cytotoxic activity. These results
      indicate that the antitumour activity of the mistletoe drug is due to a
      modulation of the tumour-host relationship, mediated by direct cytotoxicity of
      the drug to tumour cells and/or through a potentiation of immune response by
      certain, as yet unidentified, growth modifying humoral factors of the host.

PMID- 9179363
TI  - Stimulation of antitumour immunity by intrapleural instillation of a Viscum album
      L. extract.
AB  - Intrapleural administration of mistletoe extracts is reported to result in
      pleurodesis in cancer patients with malignant pleural effusions. In a recent
      study, 20 consecutive cancer patients with malignant pleural effusions were
      treated intrapleurally with the mistletoe extract Helixor. The overall response
      rate for pleurodesis was 72%, with only 1.2% displaying side effects of the World
      Health Organization classification I. The decline of tumour cells in the effusion
      liquid correlated negatively with the number of instillations. However, the
      elimination of tumour cells was associated with a transient increase in
      macrophages and eosinophils, and a constant increase in CD8+T cells. Compared to
      the responder group, the non-responders exhibited high proportions of
      macrophages, CD8+T cells and T cells with human leukocyte antigens with DR
      specificity (HLA-DR) in the effusion liquid, compatible with a disturbance of
      macrophage/T cell co-operation and thus failure to eliminate the malignant cells.
      The preliminary results suggest that mistletoe-mediated pleurodesis is due to a
      stimulation of antitumour immunity rather than mechanical sclerosis.

PMID- 9179364
TI  - Viscum album L. preparation Isorel modifies the immune response in normal and in
      tumour-bearing mice.
AB  - The Viscum album (mistletoe) preparation Isorel is able to destroy tumour cells
      and to modify immune reactivity against a particular antigen in normal and in
      tumour-bearing animals. CBA/HZgr mice and methylcholanthrene-induced fibrosarcoma
      were used in these studies. A single dose of Isorel M (140 mg/kg or 1400 mg/kg
      body weight) significantly increased the number of plaque forming cells if
      applied at the time of injection of sheep red blood cells or 1 day earlier. The
      application of Isorel 1 day after sheep red blood cells did not modify the number
      of plaque forming cells in comparison to the controls. The higher the dose of
      Isorel the stronger is the immune response to sheep red blood cells. Furthermore,
      one dose of Isorel (140 mg/kg body weight) restored the suppressed immune
      response of fibrosarcoma-bearing mice to a significant extent. Besides
      modification of the humoral immune response, the survival time of C57BI/GoZgr
      male skin grafts on syngeneic female recipients was significantly shorter if
      Isorel was applied at a particular time after grafting. However, according to
      plaque forming cell numbers, a prolonged application of Isorel was significantly
      immunosuppressive in normal mice and particularly in tumour-bearing mice. It
      should be mentioned that the doses of Isorel used in this experiment were much
      higher than generally used in cancer patients. In view of the immunomodulating
      effects of Isorel, the monitoring of the immune response of the patients treated
      with mistletoe preparations is to be recommended.

PMID- 9179365
TI  - Stimulation of the specific immune system by mistletoe extracts.
AB  - We have investigated the in vitro responsiveness of T cells from mistletoe
      treated cancer patients and untreated donors to various preparations of mistletoe
      extracts. Proliferation of peripheral blood mononuclear cells from treated but
      not from untreated patients was observed in response to therapeutically used
      mistletoe extracts prepared from apple (mali) or pine (pini) host trees. The
      strongest proliferation was induced by vesicle preparation of mali extract. Using
      a newly developed flow cytometry assay (standard cell dilution assay), we
      determined that cell growth was restricted to CD4+ T cells. Analysis with a panel
      of monoclonal antibodies against variable regions of the T cell receptor beta
      chain (V beta) revealed an oligoclonal pattern of CD4+ T cell activation. These
      results indicate that therapeutic administration of mistletoe extracts sensitized
      a restricted set of CD4+ T lymphocytes in mistletoe-treated patients. Lymphocytes
      from untreated donors are only stimulated with heat-treated mistletoe extracts.
      The responding T cells are gamma delta T cells and express variable T cell
      receptor elements V gamma 9 and V delta 2. The gamma delta-stimulating activity
      of heat-treated mistletoe extracts is sensitive to treatment with alkaline
      phosphatase but not with proteinase K, indicating that the ligands are non
      proteinaceous phosphate-containing compounds.

PMID- 9179366
TI  - Mistletoe extract-induced effects on immunocompetent cells: in vitro studies.
AB  - Cytotoxic as well as immunomodulatory effects of mistletoe extracts and their
      components have been described and seem to depend upon the host tree, the
      manufacturing process and the composition of the different components present in
      the extracts. In vitro studies showed that a fermented mistletoe extract derived
      from Viscum album L. grown on pine trees was less cytotoxic to peripheral blood
      mononuclear cells (PBMC) than other preparations. This finding could be related
      to its very low content of mistletoe lectins. Furthermore, this extract
      stimulated PBMC from healthy and especially allergic donors who had never
      received any mistletoe treatment. By analysing these in vitro reactions, an
      involvement of CD4+ T helper cells and CD14+ monocytes/macrophages was observed,
      suggesting an interaction of the specific and nonspecific immune system. In the
      supernatants of stimulated PBMC from healthy individuals, type-1 (interferon
      gamma and interleukin-2) and type-2 (interleukin-4 and interleukin-5) associated
      cytokines were detected in about 20%. In patients with colorectal tumours,
      however, reduced frequency, suggesting a functional impairment of certain
      immunocompetent cells in these patients. These studies may help to evaluate
      properties of the natural and the specific immune system.

PMID- 9179367
TI  - Immunomodulatory effects of Viscum album agglutinin-I on natural immunity.
AB  - In 24 h cultured human peripheral blood mononuclear cells, treated with various
      (1 microgram/ml to 1 ng/ml) concentrations of Viscum album agglutinin-I,
      quantitative assessment of DNA breaks labelled with terminal deoxynucleotidyl
      transferase revealed a dose-dependent Viscum album agglutinin-I-induced apoptosis
      above a lectin concentration of 10 ng/ml. After 24 h incubation of peripheral
      blood mononuclear cells with non-cytotoxic concentrations of Viscum album
      agglutinin-I (10 and 1 ng/ml), messenger (m)RNA expression and secretion of a
      panel of cytokines were evaluated by reverse polymerase chain reaction and by
      enzyme-linked immunosorbent assay (ELISA), respectively. The lectin induced
      expression of interleukin-1 alpha, interleukin-1 beta, interleukin-6, tumor
      necrosis factor-alpha, interferon-gamma, granulocyte-monocyte colony stimulating
      factor and interleukin-10 genes, but no expression of interleukin-2 or interferon
      gamma production could be detected. In addition, cellular components of the
      natural immune system (such as monocytes and granulocytes) bound Viscum album
      agglutinin-I molecules to a higher degree than lymphocytes. To establish the
      modulatory potency of Viscum album agglutinin-I on the natural immunity of human
      subjects, four randomized, double-blind crossover trials were performed on
      healthy volunteers. In contrast to the significant lectin-induced increases in
      number and activity of natural killer cells observed in animal models, in the
      first and second trial human healthy individuals showed no significant
      differences between their natural killer responses following an injection of
      lectin-enriched preparation or saline. Due to considerable intrinsic fluctuation
      of these parameters, a third and fourth double-blind trial with freshly isolated
      Viscum album agglutinin-I was performed using a more rapidly detectable
      parameter, the priming of granulocytes. Here, significant lectin-induced
      increases were found.

PMID- 9179368
TI  - Mistletoe therapy for human cancer: the role of the natural killer cells.
AB  - Extracts produced from Viscum album L. (mistletoe) as well as certain isolated
      components are able to stimulate different functions of the immune system. The
      natural killer cells have been suggested as one of the candidates for direct
      tumour cell destruction. These cells are defined by their ability to mediate non
      major histocompatibility complex (MHC) restricted cytotoxicity without prior
      sensitization against a specific antigen. However, their effectiveness in tumor
      defence in vivo is unclear. In general, natural killer cells are unable to lyse
      fresh autologous tumour cells in vitro unless activated by interleukin-2
      preincubation. The results of clinical studies are contradictory, but there is
      evidence that they may contribute to the prevention of the development of
      recidives and metastases. In this regard it is interesting that mistletoe
      extracts are able to stimulate natural killer cell-mediated cytotoxicity in vitro
      directly as well as indirectly in a cytokine-like manner, with the active
      components being carbohydrates rather than lectins. Clinical application of
      mistletoe extracts or isolated lectins is reported to induce augmentation of both
      number and activity of natural killer cells in peripheral blood in a dose
      dependent manner; however, non-responders also have been described. In future
      work it has to be clarified whether a mistletoe-derived modulation of the natural
      killer system is of benefit in the tumour defence of cancer patients.

PMID- 9179369
TI  - Clinical relevance of immunoactive mistletoe lectin-I.
AB  - Recent investigations have shown that defined, non-toxic doses of the galactoside
      specific mistletoe lectin (mistletoe lectin-I, a constituent of clinically
      approved plant extracts) have immunomodulatory potencies. The obvious ability of
      certain lectins (e.g. mistletoe lectin-I) to activate (non)-specific defence
      mechanisms supports the assumption that lectin-carbohydrate interactions may
      induce clinically beneficial immunomodulation. Initial clinical trials were
      promising and currently prospectively randomized multicentre trials are being
      performed to evaluate the ability of complementary mistletoe lectin-I treatment
      to reduce the rate of tumor recurrences and metastases, to improve the overall
      survival as well as the quality of life and to exert immunoprotection in cancer
      patients under tumor destructive therapy.

PMID- 9179371
TI  - Donor-dependent and dose-dependent variation in the induction of T lymphocyte
      locomotion in a three-dimensional collagen matrix system by a mistletoe
      preparation (Iscador).
AB  - Controlled activation of non-specific and specific immune defence mechanisms can
      beneficially manipulate the host's ability to attack malignant cells. In this
      context, migration and tissue distribution of immunocompetent cells may be
      prerequisites for an efficient immune surveillance. The effect of various non
      cytotoxic concentrations of the Viscum album L. (mistletoe) preparation Iscadore
      QuFrF on the locomotory activity of immunomagnetically isolated human CD4+ and
      CD8+ T lymphocytes from healthy donors was investigated. Cellular migration was
      examined within a three-dimensional collagen matrix. Donor-dependent variations
      in baseline activities of spontaneously locomoting T cells were accompanied by
      individual response patterns of T cells from different donors in the presence of
      various concentrations of mistletoe preparation (0.25-2.5 micrograms/ml). Using
      the three-dimensional collagen matrix assay an induction of locomotory activity
      was detected in a highly reproducible fashion although the optimal concentration
      of mistletoe preparation and the time point of maximal response were individual
      for each donor. Our data suggest that the direct stimulation of T-cell migration
      by mistletoe components may modulate the system of immune surveillance and
      recognition in patients under mistletoe therapy.

PMID- 9179370
TI  - Induction of anti-mistletoe lectin antibodies in relation to different mistletoe
      extracts.
AB  - Mistletoe extracts are frequently applied in adjuvant cancer treatment. The
      mistletoe lectins are especially suggested to mediate an antitumorous effect.
      During treatment with mistletoe lectin-rich extracts, anti-mistletoe lectin
      antibodies preferentially of the immunoglobulin G type are produced against
      mistletoe lectin (ML)-1. Interestingly, after application of mistletoe extracts
      containing natural micelles, anti-mistletoe lectin antibodies of the
      immunoglobulin G as well as one of the immunoglobulin E type were induced in
      parallel, suggesting that the nature and preparation of the antigens within the
      extract modifies immune responses. Anti-mistletoe lectin antibodies were shown to
      neutralize the cytotoxic effect of mistletoe lectin on peripheral blood
      mononuclear cells in vitro. Thus, the mode of application of these extracts seems
      to be of importance with respect to the therapeutic effect.

PMID- 9179372
TI  - Mistletoe therapy and immunological research.

PMID- 9179373
TI  - Characterization of human A2A adenosine receptors with the antagonist radioligand
      [3H]-SCH 58261.
AB  - 1. We have characterized the binding of the new potent and selective antagonist
      radioligand [3H]-5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4
      triazol o[1,5- c]pyrimidine, [3H]-SCH 58261, to human cloned A2A adenosine
      receptors. 2. In Chinese hamster ovary (CHO) cells transfected with the human
      cloned A2A receptor, [3H]-SCH 58261 specific binding (about 70%) was rapid,
      saturable, reversible and proportional to protein concentration. The kinetic KD
      value was 0.75 nM. Saturation experiments showed that [3H]-SCH 58261 labelled a
      single class of recognition sites with high affinity (KD = 2.3 nM) and limited
      capacity (apparent Bmax = 526 fmol mg-1 protein). 3. Competition experiments
      revealed that binding of 0.5 nM [3H]-SCH 58261 was displaced by adenosine
      receptor agonists with the following order of potency: 2-hexynyl-5'-N
      ethylcarboxamidoadenosine (2HE-NECA) > 5'-N-ethylcarboxamidoadenosine (NECA) = 2
      phenylaminoadenosine (CV 1808) > 2-[4-(2-carboxyethyl)-phenethylamino]-5'-N
      ethylcarboxamidoadenosi ne (CGS 21680) > R-N6-phenylisopropyladenosine (R-PIA) >
      or = N6-cyclohexyladenosine (CHA) > S-N6-phenylisopropyladenosine (S-PIA). 4.
      Adenosine receptor antagonists inhibited [3H]-SCH 58261 binding with the
      following order: 5-amino-9-chloro-2-(2-furyl)-[1,2,4]-triazolo[1,5-c] quinazoline
      (CGS 15943) > SCH 58261 > xanthine amine congener (XAC) > (E,18%-Z,82%)7-methyl-8
      (3,4-dimethoxystyryl)-1,3- dipropylxanthine (KF 17837S) > 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) > theophylline. 5. Affinity values and rank order of
      potency of both receptor agonists and antagonists were similar to those
      previously obtained in human platelet and rat striatal membranes, except for CV
      1808 which was more potent than CGS 21680. SCH 58261 was a competitive antagonist
      at inhibiting NECA-induced adenosine 3':5'-cyclic monophosphate (cyclic AMP)
      accumulation in CHO cells transfected with human A2A receptors. Good agreement
      was found between binding and functional data. 6. Thus, the new antagonist
      radioligand is preferable to the receptor agonist radioligand [3H]-CGS 21680
      hitherto used to examine the pharmacology of human cloned A2A adenosine
      receptors.

PMID- 9179374
TI  - Beta 2-adrenoceptor agonist-mediated inhibition of human airway smooth muscle
      cell proliferation: importance of the duration of beta 2-adrenoceptor
      stimulation.
AB  - 1. Airway hyperresponsiveness in asthma has been ascribed to airway wall
      thickening as a result of smooth muscle proliferation and hypertrophy. We have
      previously shown that continuous exposure to the beta 2-adrenoceptor agonist,
      salbutamol inhibits mitogen-induced proliferation of airway smooth muscle cells.
      In the present study, the effects of variable durations and repeated periods of
      exposure to beta 2-adrenoceptor agonists on DNA synthesis in human cultured
      airway smooth muscle have been investigated to model some of the possible
      pharmacokinetic profiles of these agents following inhalation. DNA synthesis was
      measured by [3H]-thymidine incorporation. 2. Shorter periods of exposure (up to
      2.5 h) of airway smooth muscle cells to salbutamol (100 nM) commencing 30 min
      before thrombin (0.3 u ml-1) stimulation had no effect on the subsequent increase
      in [3H]-thymidine incorporation. However, inhibition by salbutamol was evident
      with a 4.5 h exposure and was maximal after an 8.5 h exposure. Similar patterns
      of results were observed when fenoterol (100 nM) was used in place of salbutamol
      as the beta 2-adrenoceptor agonist or when epidermal growth factor (300 pM) was
      used in place of thrombin as the mitogen. Salbutamol had no effect on thrombin
      stimulated [3H]-leucine incorporation after 8.5 h of exposure, but a
      statistically significant effect was observed after 48 h of exposure. 3.
      Experiments in which DNA synthesis was measured up to 52 h after the addition of
      thrombin indicated that exposure to salbutamol during the first 8 h of mitogen
      stimulation delayed rather than inhibited the DNA synthesis. 4. Addition of
      salbutamol (100 nM) at different times either before or up to 24 h after the
      addition of thrombin indicated that [3H]-thymidine incorporation (measured
      between 24 and 28 h after thrombin) could be significantly attenuated when
      salbutamol was added as late as 18 h after the addition of thrombin. 5. The
      effects of more prolonged exposure to salbutamol were investigated by the
      addition of salbutamol for either 15 or 24 h per day for a total of 3 days. There
      were no significant differences in the level of inhibition of thrombin-stimulated
      [3H]-thymidine incorporation between continuous and intermittent salbutamol over
      the 3 day period and the inhibition was also not different to that achieved with
      a single continuous exposure to salbutamol over 28 h. 6. These results indicate
      that although exposure to beta 2-adrenoceptor agonists during the first 8 h of
      mitogen stimulation does not have a sustained inhibitory effect on DNA synthesis,
      repeated intermittent or prolonged continuous exposures to salbutamol do inhibit
      DNA synthesis, without evidence of marked desensitization.

PMID- 9179375
TI  - Effects of chronic growth hormone treatment in aged rats on the biophysical and
      pharmacological properties of skeletal muscle chloride channels.
AB  - 1. The effects of a 4-month daily treatment with recombinant human growth hormone
      (GH) (150 micrograms kg-1) to aged rats were evaluated on the passive and active
      membrane electrical properties of extensor digitorum longus (EDL) muscle fibres
      in vitro by means of a two intracellular microelectrode technique. 2. Chronic GH
      treatment completely restored the diameter and the membrane capacitance of aged
      EDL muscle fibres and significantly lowered the membrane resistance towards the
      adult value. There was also an increase of the threshold current, a shortening of
      the latency and an increase of the amplitude of the action potential and a
      significant amelioration of the membrane firing capability. 3. The effects were
      almost fully attributable to a significant 50% increase of resting conductance to
      chloride ions (GCl), although an observed restoration of potassium conductance
      and a possible effect on voltage-activated sodium channels could contribute to
      the effects. 4. EDL muscle fibres of untreated aged rats showed a different
      pharmacological response to 2-(p-chlorophenoxy) propionic acid (CPP) enantiomers
      from that seen in adult rats; the S-(-) isomer was less potent in blocking GCl
      and the R-(+) isomer always increased GCl instead of producing the typical
      biphasic effect observed in adult fibres (an increase of GCl at 1-10 microM and a
      decrease at higher concentrations). The 4-month-GH-treated aged rats showed a
      pharmacological sensitivity to CPP enantiomers similar to that of adults. 5. The
      in vitro application of insulin-like growth factor I (IGF-I), the peripheral
      mediator of GH, produced a significant and irreversible increase of GCl of EDL
      muscle of EDL muscle of untreated aged rats, an effect not observed in adults.
      This effect was completely inhibited by preincubation with 0.5 microM okadaic
      acid, suggesting that the IGF-I receptor transduction pathway can act on the
      phosphorylation state of the chloride channel through a serine-threonine protein
      phosphatase. 6. The results show that the skeletal muscle chloride channel is a
      target of the impairment of GH/IGF-I axis occurring in aged subjects. The acute
      and chronic effects observed on GCl of aged muscle fibres suggest that the GH/IGF
      I stimuli act through a modulation of channel phosphorylation state and through
      the synthesis of 'adult'-like type chloride channels.

PMID- 9179376
TI  - Role of tachykinins in castor oil diarrhoea in rats.
AB  - 1. We set out to ascertain the role of tachykinins, neurokinin A and substance P,
      in castor oil-induced diarrhoea in rats as disclosed by the inhibitory effect of
      the non-peptide NK1- and NK2-receptor antagonists. SR 140333 and SR 48968,
      respectively. 2. SR 48968 (0.02 to 20 micrograms kg-1, s.c. or p.o.), and the
      opioid receptor agonist loperamide (1-10 mg kg-1, p.o.), dose-dependently
      prevented castor oil effects: % inhibition vs castor oil, diarrhoea 0 to 100,
      increase in faecal mass 7 to 90 and water content 16 to 90. SR 140333 (0.02 to 20
      micrograms kg-1, s.c.) and the platelet activating factor antagonist SR 27417 (5
      to 500 micrograms kg-1, p.o.) did not prevent the increase in faecal water
      content, but reduced faecal mass (35 to 66%) and diarrhoea (0 to 57%). 3. The R
      enantiomers of tachykinin NK1 and NK2 receptor antagonists, SR 140603 and SR
      48605 (both at 2 or 20 micrograms kg-1, s.c.) had no effect other than reducing
      faecal mass at the highest dose tested. 4. SR 48968 (20 micrograms kg-1, p.o.)
      but not loperamide (10 mg kg-1, p.o.) given 24 h before castor oil, still
      slightly but significantly reduced by 30% the increase of faecal mass output;
      both treatments significantly reduced (30 to 70%) the effect of castor oil on
      faecal water content, although the incidence of diarrhoea was only slightly less
      than in controls. 5. In castor oil-treated rats, naloxone (2 mg kg-1, s.c.)
      completely blocked the antidiarrhoeal action of loperamide (10 mg kg-1, p.o.) but
      not of SR 48968 (20 micrograms kg-1, p.o.): a similar result was obtained on
      faecal mass and water content. 6. Castor oil strongly increased the occurrence of
      manometrically recorded propulsive giant contractions (500 to 1000% over control
      values) of transverse and distal colon, this effect being significantly prevented
      (80 to 100%) by SR 48968 and loperamide and partially by SR 140333 (35% distal
      colon, 70% transverse colon). 7. In castor oil free rats, loperamide but not SR
      48968 or SR 140333 significantly reduced by 50% the gastrointestinal transit of a
      charcoal test meal, as well as 24 h faecal mass output. Consistently, loperamide,
      unlike the tachykinin receptor antagonists, had a dramatic effect on manometric
      recordings of intestinal motility, reducing all kinds of colonic contractions. 8.
      Our findings suggest that castor oil diarrhoea in rats entails activation of NK1
      and NK2 receptors by endogenous tachykinins, whose antagonists may have a
      potential as antidiarrhoeal agents free from the constipating action of opioids.

PMID- 9179377
TI  - Effects of N- and L-type calcium channel antagonists and (+/-)-Bay K8644 on nerve
      induced catecholamine secretion from bovine perfused adrenal glands.
AB  - 1. The effects of N- and L-type calcium channel antagonists and (+/-)-Bay K8644
      on catecholamine release from chromaffin cells and acetylcholine release from
      splanchnic nerve terminals was investigated in bovine perfused adrenal glands. 2.
      Adrenal glands were perfused retrogradely and preloaded with [3H]-choline.
      Subsequent efflux of 3H-labelled compounds was taken as an index of acetylcholine
      release from the splanchnic nerve terminals. Noradrenaline and adrenaline release
      from the glands was measured by h.p.l.c. with electrochemical detection. 3. A
      maximally effective frequency of field stimulation of the adrenal nerves, 10 Hz,
      induced release of catecholamines and 3H-labelled compounds. Tetrodotoxin (1
      microM) abolished release of both catecholamines and 3H-labelled compounds. A
      combination of mecamylamine (5 microM) and atropine (1 microM) inhibited nerve
      induced catecholamine release by about 75% but did not inhibit release of 3H
      labelled compounds. Reducing the concentration of extracellular calcium 5 fold to
      0.5 mM inhibited nerve-induced catecholamine release by 80% and release of 3H
      labelled compounds by 50%. 4. (+/-)-Bay K8644 (1 microM), nitrendipine (1
      microM), omega-conotoxin-GVIA (10 nM) and the combination of nitrendipine and
      omega-conotoxin-GVIA each had no effect on nerve-induced release of 3H-labelled
      compounds. 5. (+/-)-Bay K8644 (1 microM) potentiated nerve-induced catecholamine
      release by 75%. Nitrendipine (1 microM) reduced release by 20% but this did not
      reach statistical significance, omega-Conotoxin-GVIA (10 nM) reduced nerve
      induced catecholamine release by 75%, while the combination of omega-conotoxin
      GVIA and nitrendipine reduced release to the same extent as omega-conotoxin-GVIA
      alone. 6. Exogenous acetylcholine perfusion through the glands produced a
      concentration-dependent increase in catecholamine release. The maximally
      effective concentration of acetylcholine for catecholamine release was > or = 300
      microM, while 30 microM acetylcholine gave comparable catecholamine release to
      that obtained with 10 Hz field stimulation. 7. (+/-)-Bay K8644 (1 microM),
      nitrendipine (1 microM) and omega-conotoxin-GVIA (10 nM) each had no significant
      effect on catecholamine release evoked by perfusion of the gland with either a
      near maximally effective concentration of acetylcholine, 100 microM, or with the
      lower concentration of 30 microM. 8. The results show that the omega-conotoxin
      GVIA-sensitive N-type voltage-sensitive calcium channels located on the
      chromaffin cells are largely responsible for catecholamine release induced by
      nerve stimulation in bovine adrenal glands. In contrast, N-type calcium channels
      are not involved in catecholamine release induced by exogenous acetylcholine. L
      type voltage sensitive calcium channels do not play a major role in nerve-induced
      or exogenously applied acetylcholine-induced catecholamine release. However, the
      L-type calcium channels do have the potential to augment powerfully nerve-induced
      catecholamine release. N- and L-type calcium channels do not play a major role in
      the presynaptic release of acetylcholine.

PMID- 9179378
TI  - Cytochrome P450 1A-like proteins expressed in the islets of Langerhans and
      altered pancreatic beta-cell secretory responsiveness.
AB  - 1. The cytochrome P450 (CYP) mixed-function oxidase system is widely distributed
      in body tissues and plays a key role in the metabolism of endogenous and
      exogenous compounds. Little attention has been paid to the expression of the
      system in the islets of Langerhans. The current study has examined the expression
      and potential role of the CYP1A family within the islets of Langerhans of control
      and 3-methylcholanthrene (3-MC)-induced Wistar rats. 2. CYP1A expression within
      pancreatic slices and islets from 3-MC-induced and control rats demonstrated that
      CYP1A-like protein levels were induced by 3-MC pretreatment (25 mg kg-1 day-1;
      i.p. for 3 days). 3. Effects of 3-MC-induction on beta-cell secretory
      responsiveness were investigated by use of rat collagenase-isolated islets.
      Insulin release from control islets incubated with 3 mM glucose (basal) was 1.4
      +/- 0.2 ng/islet h-1 (mean +/- s.e.mean, n = 7). Incubation with 16.7 mM glucose,
      25 mM KCl, 100 microM arachidonic acid, or 100 microM carbachol caused a 4.4,
      7.0, 4.0 and 4.2 fold, respectively, increase in insulin release (P < 0.001).
      Forskolin (2 microM), or phorbol 12-myristic 13-acetate (10 nM) potentiated
      glucose-stimulated insulin release 1.2 and 1.6 fold (P < 0.01) whereas adenalin
      (1 microM) caused a 76% inhibition (P < 0.01). 4. Islets from 3-MC pretreated
      animals displayed similar responsiveness to all agents tested except arachidonic
      acid, carbachol and forskolin. Insulin release in response to arachidonic acid
      and carbachol was enhanced 5.2 and 5.0 fold, respectively, by 3-MC pretreatment
      (P < 0.001 compared to control islets incubated with 3 mM glucose); the effect of
      forskolin on insulin output was significantly decreased (20%; P < 0.01) compared
      to control islets. 5. 3-MC pretreatment did not cause any significant differences
      in food intake, plasma glucose or total islet insulin content. Incubation of
      islets with 3-MC in vitro (1 microM - 10 mM) did not affect basal or glucose
      stimulated insulin release. 6. These data suggest that CYP1A-like protein
      expression within the pancreatic islets of Langerhans is inducible and may have a
      role in the alteration of pancreatic beta-cell secretory responsiveness.

PMID- 9179379
TI  - Inhibition of arginase in rat and rabbit alveolar macrophages by N omega-hydroxy
      D,L-indospicine, effects on L-arginine utilization by nitric oxide synthase.
AB  - 1. Alveolar macrophages (AM phi) exhibit arginase activity and may, in addition,
      express an inducible form of nitric oxide (NO) synthase (iNOS). Both pathways may
      compete for the substrate. L-arginine. The present study tested whether two
      recently described potent inhibitors of liver arginase (N omega-hydroxy-D,L
      indospicine and 4-hydroxyamidino-D,L-phenylalanine) might also inhibit arginase
      in AM phi and whether inhibition of arginase might affect L-arginine utilization
      by iNOS. 2. AM phi obtained by broncho-alveolar lavage of rat and rabbit isolated
      lungs were disseminated (2.5 or 3 x 10(6) cells per well) and allowed to adhere
      for 2 h. Thereafter, they were either used to study [3H]-L-arginine uptake (37
      kBq, 0.1 microM, 2 min) or cultured for 20 h in the absence or presence of
      bacterial lipopolysaccharide (LPS). Cultured AM phi were incubated for 1 h with
      [3H]-L-arginine (37 kBq, 0.1 microM) and the accumulation of [3H]-L-citrulline
      (NOS activity) and [3H]-L-ornithine (arginase activity) was determined. 3. During
      1 h incubation of rabbit AM phi with [3H]-L-arginine, no [3H]-L-citrulline, but
      significant amounts of [3H]-L-ornithine (150 d.p.m x 1000) were formed. N omega
      hydroxy-D,L-indospicine and 4-hydroxyamidino-D,L-phenylalanine, present during
      incubation, concentration-dependently reduced [3H]-L-ornithine formation (IC50: 2
      and 45 microM, respectively). 4. N omega-hydroxy-D,L-indospicine (up to 100
      microM) had no effect on [3H]-L-arginine uptake into rabbit AM phi, whereas 4
      hydroxyamidino-D,L-phenylalanine caused a concentration-dependent inhibition
      (IC50: 300 microM). 5. Rat AM phi, cultured in the absence of LPS, formed
      significant amounts of [3H]-L-citrulline and [3H]-L-ornithine (133 and 212 d.p.m
      x 1000, respectively) when incubated for 1 h with [3H]-L-arginine. When AM phi
      had been cultured in the presence of 0.1 or 1 microgram ml-1 LPS, the formation
      of [3H]-L-citrulline was enhanced by 37 +/- 8.3 and 99 +/- 12% and that of [3H]-L
      ornithine reduced by 21 +/- 8.7 and 70 +/- 2.5%, respectively. 6. In rat AM phi,
      cultured in the absence or presence of LPS, N omega-hydroxy-D,L-indospicine (10
      and 30 microM) greatly reduced formation of [3H]-L-ornithine (by 80-95%) and this
      was accompanied by increased formation of [3H]-L-citrulline. However, only 20-30%
      of the [3H]-L-arginine not metabolized to [3H]-L-ornithine after inhibition of
      arginase was metabolized to [3H]-L-citrulline, when the AM phi had been cultured
      in the absence of LPS (i.e. low level of iNOS). On the other hand, when the AM
      phi had been cultured in the presence of LPS (i.e. high level of iNOS), all the
      [3H]-L-arginine not metabolized by the inhibited arginase was metabolized to [3H]
      L-citrulline. 7. In conclusion, N omega-hydroxy-D,L-indospicine is a potent and
      specific inhibitor of arginase in AM phi. In cells in which, in addition to
      arginase, iNOS is expressed, inhibition of arginase can cause a shift of L
      arginine metabolism to the NOS pathway. However, the extent of this shift appears
      to depend in a complex manner on the level of iNOS.

PMID- 9179380
TI  - Characterization of nociceptin hyperalgesia and allodynia in conscious mice.
AB  - 1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine
      induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin
      evoked hyperalgesia in response to noxious thermal stimuli in conscious mice.
      Here we have characterized the nociceptin-induced allodynia and compared it with
      the morphine-induced allodynia and the nociceptin-evoked hyperalgesia. 2.
      Nociceptin-induced allodynia was evoked by the first stimulus 5 min after i.t.
      injection, reached a maximum at 10 min, and continued for a 50 min experimental
      period. Dose-dependency of the allodynia showed a bell-shaped pattern from 50 pg
      to 5 ng kg-1, and the maximum effect was observed at 2.5 ng kg-1. 3. Morphine
      induced allodynia reached the maximum effect at 15 min and declined progressively
      until cessation by 40-50 min. The dose-response curve showed a bell-shaped
      pattern, similar to that induced by nociceptin, with a maximum effect at 0.5 mg
      kg-1, five orders of magnitude higher than that of nociceptin. 4. The allodynia
      evoked by nociceptin and morphine were dose-dependently blocked by glycine, D(-)
      2-amino-5-phosphonovaleric acid (D-AP5, an N-methyl-D-aspartate (NMDA) receptor
      antagonist), gamma-D-glutamylaminomethyl sulphonic acid (GAMS, a non-NMDA
      receptor antagonist) and methylene blue (a soluble guanylate cyclase inhibitor),
      but were not affected by muscimol (a gamma-aminobutyric acidA (GABAA) receptor
      agonist) and baclofen (a GABAB receptor agonist). 5. Morphine did not inhibit
      forskolin-stimulated cyclicAMP formation in cultured cells expressing the
      nociceptin receptor. 6. Nociceptin-induced hyperalgesia was evoked 10-15 min
      after i.t. injection. Nociceptin produced a monophasic hyperalgesic action over a
      wide range of doses from 5 fg to 50 ng kg-1. The nociceptin-induced hyperalgesia
      was blocked by glycine only among the agents examined. 7. None of the pain
      responses evoked by nociceptin and morphine were blocked by naloxone. 8. These
      results demonstrate that, whereas the mechanisms of the nociceptin-induced
      allodynia and hyperalgesia are evidently distinct, they involve a common
      neurochemical event beginning with the disinhibition of the inhibitory
      glycinergic response. Morphine may induce allodynia through a pathway common to
      nociceptin, but the nociceptin receptor does not mediate the action of high doses
      of morphine.

PMID- 9179381
TI  - Investigation of the inhibition by acetylshikonin of the respiratory burst in rat
      neutrophils.
AB  - 1. The ability of acetylshikonin to inhibit the respiratory burst in rat
      neutrophils was characterized and the underlying mechanism of action was also
      assessed in the present study. 2. Acetylshikonin caused an irreversible and a
      concentration-dependent inhibition of formylmethionylleucyl-phenylalanine (fMLP)
      plus dihydrocytochalasin B (CB)- and phorbol 12-myristate 13-acetate (PMA)
      induced superoxide anion (O2.-) generation with IC50 values of 0.48 +/- 0.03 and
      0.39 +/- 0.03 microM, respectively. Acetylshikonin also inhibited the O2
      consumption in neutrophils in response to fMLP/CB as well as to PMA. 3.
      Acetylshikonin did not scavenge the generated O2.- in the xanthine-xanthine
      oxidase system or during dihydroxyfumaric acid (DHF) autoxidation but, on the
      contrary, acetylshikonin enhanced the O2.- generation in these cell-free oxygen
      radical generating systems. 4. Acetylshikonin inhibited the formation of inositol
      trisphosphate (IP3) (39.0 +/- 7.8% inhibition at 10 microM, P < 0.05) in
      neutrophils in response to fMLP. 5. Both the neutrophil cytosolic protein kinase
      C (PKC) activity and the PMA-induced PKC associated with the membrane were
      unaffected by acetylshikonin. 6. Acetylshikonin did not affect the porcine heart
      protein kinase A (PKA) activity. Upon exposure to acetylshikonin, the cellular
      cyclic AMP level was decreased in neutrophils in response to fMLP. 7. The
      cellular formation of phosphatidic acid (PA) and, in the presence of ethanol,
      phosphatidylethanol (PEt) induced by fMLP/CB were inhibited by acetylshikonin
      (60.1 +/- 7.3 and 63.2 +/- 10.5% inhibition, respectively, at 10 microM, both P <
      0.05). Moreover, acetylshikonin attenuated the fMLP/CB-induced protein tyrosine
      phosphorylation (about 90% inhibition at 1 microM). 8. In PMA-activated
      neutrophil particulate NADPH oxidase preparations, acetylshikonin did not
      inhibit, but enhanced, the O2.- generation in the presence of NADPH. However,
      acetylshikonin decreased the membrane associated p47phox in PMA-activated
      neutrophils (about 60% inhibition at 1 microM). 9. Collectively, these results
      suggest that the attenuation of protein tyrosine phosphorylation and a failure in
      the assembly of a functional NADPH oxidase complex probably contribute
      predominantly to the inhibition of respiratory burst in neutrophils by
      acetylshikonin. In contrast, the blockade of phospholipase C (PLC) and
      phospholipase D (PLD) pathways play only a minor role in this respect.

PMID- 9179382
TI  - Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of
      tumour necrosis factor alpha.
AB  - 1. Peripheral inflammation is characterized by heightened pain sensitivity. This
      hyperalgesia is the consequence of the release of inflammatory mediators,
      cytokines and growth factors. A key participant is the induction of the
      neurotrophin nerve growth factor (NGF) by interleukin-1 beta (IL-1 beta). 2.
      Tumour necrosis factor alpha (TNF alpha) has been shown both to produce
      hyperalgesia and to upregulate IL-1 beta. We have now examined whether the
      induction of TNF alpha in inflammatory lesions contributes to inflammatory
      sensory hypersensitivity by inducing IL-1 beta and NGF. 3. The intraplantar
      injection of complete Freund's adjuvant (CFA) in adult rats produced a localized
      inflammation of the hindpaw with a rapid (3 h) reduction in withdrawal time in
      the hot plate test and in the mechanical threshold for eliciting the flexion
      withdrawal reflex. 4. The CFA-induced inflammation resulted in significant
      elevation in the levels of TNF alpha, IL-1 beta and NGF in the inflamed paw. In
      the case of TNF alpha, an elevation was detected at 3 h, rose substantially at 6
      h, peaked at 24 h and remained elevated at 5 days, with similar but smaller
      changes in the contralateral non-inflamed hindpaw. No increase in serum TNF alpha
      was detected at 24 h post CFA injection. 5. Intraplantar recombinant murine TNF
      alpha injections produce a short-lived (3-6 h) dose-dependent (50-500 ng)
      increase in thermal and mechanical sensitivity which was significantly attenuated
      by prior administration of anti-NGF antiserum. 6. Intraplantar TNF alpha (100-500
      ng) also elevated at 6 but not 48 h the levels of IL-1 beta and NGF in the
      hindpaw. 7. A single injection of anti-TNF alpha antiserum, 1 h before the CFA,
      at a dose sufficient to reduce the effects of a 100 ng intraplantar injection of
      TNF alpha, significantly delayed the onset of the resultant inflammatory
      hyperalgesia and reduced IL-1 beta but not NGF levels measured at 24 h. 8. The
      elevation of TNF alpha in inflammation, by virtue of its capacity to induce IL-1
      beta and NGF, may contribute to the initiation of inflammatory hyperalgesia.

PMID- 9179383
TI  - Modulation of excitatory synaptic transmission by nociceptin in superficial
      dorsal horn neurones of the neonatal rat spinal cord.
AB  - 1. The modulatory actions of nociceptin/orphanin FQ on excitatory synaptic
      transmission were studied in superficial dorsal horn neurones in transverse
      slices from 7 to 14 day old rats. 2. Glutamatergic excitatory postsynaptic
      currents (e.p.s.cs) were recorded from the somata of the neurones in the whole
      cell patch-clamp configuration. E.p.s.cs were evoked by extracellular electrical
      stimulation (100 microns, 3-10 V) of the ipsilateral dorsal root entry zone by
      use of a glass electrode. E.p.s.cs with constant short latency (< 2.3 ms) and
      with no failures upon stimulation were assumed to be monosynaptic. These e.p.s.cs
      occurred with an average latency of 1.72 +/- 0.098 ms and exhibited a fast decay
      with a time constant, tau, of 4.8 +/- 0.53 ms (n = 30). 3. Nociceptin reversibly
      reduced the amplitudes of e.p.s.cs in a concentration-dependent manner in 25 out
      of 27 cells tested. Average maximum inhibition was 51.6 +/- 5.7% (mean +/-
      s.e.mean; n = 9), at concentrations > 3 microM. EC30 was 485 +/- 47 nM and the
      Hill coefficient was 1.29 +/- 0.09. 4. Inhibition of synaptic transmission by
      nociceptin (10 microM) was insensitive to the non-specific opioid receptor
      antagonist naloxone (10 microM) indicating that nociceptin did not act via
      classical opioid receptors. 5. In order to determine the site of action of
      nociceptin spontaneous miniature e.p.s.cs (m-e.p.s.cs) were recorded. Nociceptin
      reduced the frequency of m-e.p.s.cs in 6 out of 7 cells but had no effect on
      their amplitude distribution or on their time course. These findings suggest a
      pre- rather than a postsynaptic modulatory site of action. This is in line with
      the finding that current responses elicited by extracellular application of L
      glutamate (10 microM) were not affected by nociceptin (10 microM; n = 7). 6. No
      positive correlation was found between the degree of inhibition by nociceptin (10
      microM) and by the mixed delta- and mu-receptor agonist methionine-enkephalin (10
      microM). This suggests that both neuropeptides acted on different but perhaps
      overlapping populations of synaptic connections. 7. Our results indicate that
      nociceptin inhibits excitatory synaptic transmission in the superficial layers of
      the rat dorsal horn by acting on presynaptic, presumably ORL1 receptors. This may
      be an important mechanism for spinal sensory information processing including
      nociception.

PMID- 9179384
TI  - Cyclosporine A-induced increase in glomerular cyclic GMP in rats and the
      involvement of the endothelinB receptor.
AB  - 1. A transient two fold increase in the cyclic GMP content was observed in rat
      freshly isolated glomeruli 6 to 9 h after a single subcutaneous injection of 20
      mg kg-1 cyclosporine A (CsA) in conscious animals. 2.In vitro stimulation with
      endothelin 3 (ET-3) of isolated glomeruli obtained from CsA-untreated rats
      resulted in a dose-dependent increase in cyclic GMP content. The increase
      observed with 10 nM ET-3 was similar to that observed in glomeruli isolated 9 h
      after in vivo CsA administration. 3. The rise in glomerular cyclic GMP content
      after in vivo CsA injection was prevented by in vivo treatment with L-NAME (10 mg
      kg-1) or by in vitro calcium deprivation of the incubation medium. 4. The
      stimulating effects of CsA on glomerular cyclic GMP content were inhibited by in
      vivo administration of the ETB receptor antagonist BQ-788 (2 mg kg-1) but not by
      the ETA receptor antagonist BQ-123 (2 mg kg-1). 5. The maximum increase in
      glomerular cyclic GMP content induced in vitro by acetylcholine (100 microM) and
      by ET-3 (100 nM) was slightly lower (approximately by 20-25%; P < 0.05) in
      glomeruli from CsA-treated rats than in glomeruli from untreated rats. In
      contrast, the maximum increase achieved with 1 microM sodium nitroprusside was
      similar in both groups. 6. A single subcutaneous injection of CsA did not
      significantly alter the glomerular mRNA expression of constitutive endothelial NO
      synthase (eNOS), as evaluated by RT-PCR, whereas the mRNA expression of the
      inducible NO synthase (iNOS), which follows pretreatment with lipopolysaccharide,
      was prevented. 7. These results indicate that in vivo administration of a single
      dose of cyclosporine A transiently increases the cyclic GMP content of freshly
      isolated glomeruli, and that activation of ETB receptors and stimulation of the
      NO pathway are involved in this process. Furthermore, a single administration of
      CsA does not impair eNOS mRNA expression and only slightly reduces NO-dependent
      glomerular cyclic GMP production.

PMID- 9179385
TI  - Evidence for specific regional patterns of responses to different
      vasoconstrictors and vasodilators in sheep isolated pulmonary arteries and veins.
AB  - 1. Responses of large (5-7 mm in diameter) and medium sized (3-4 mm in diameter)
      branches of sheep isolated intrapulmonary arteries and veins and three groups of
      small pulmonary arteries (200, 500 and 1000 microns diameter) to the
      vasoconstrictors endothelin-1, 5-hydroxytryptamine (5-HT), noradrenaline and the
      thromboxane A2 mimetic, U46619, were examined. Also, relaxation responses to the
      endothelium-dependent vasodilators, acetylcholine (ACh), bradykinin and ionomycin
      and the endothelium-independent vasodilator, sodium nitroprusside (SNP), were
      studied to determine their predominant site of action within the pulmonary
      vasculature. 2. Endothelin-1 was the most potent vasoconstrictor tested in all
      vessels. The maximum response to endothelin-1, expressed as a percentage of the
      maximum contraction to KC1 depolarization, did not differ significantly between
      the different vessels. By contrast, pulmonary arteries greater than 200 microns
      in diameter failed to contract to U46619, whereas U46619 was a potent constrictor
      of large and medium-sized veins. 3. 5-HT caused similar contractions in all
      arteries > 200 microns in diameter, but the maximum response was significantly
      diminished in smaller arteries. By contrast, the maximum response to
      noradrenaline was progressively attenuated with decreasing arterial diameter.
      Both 5-HT and noradrenaline caused poor contractions in veins. Pulmonary veins
      were less sensitive to 5-HT than arteries and at low concentrations 5-HT caused
      relaxation. No change in sensitivity to noradrenaline was noted between the
      arteries and veins. 4. Relaxation responses to bradykinin and ionomycin decreased
      progressively along the pulmonary vascular tree and were nearly absent in large
      veins. Also, ACh was a poor relaxing agent of large and medium-sized arteries and
      failed to mediate any relaxation response in other vessel segments. Surprisingly
      the smallest arteries examined (approximately 200 microns in diameter) failed to
      relax to ionomycin, bradykinin and SNP. However, both the sensitivity and maximum
      relaxation to SNP were similar in all other arterial and venous segments. 5. In
      conclusion, marked regional differences in reactivity to both vasoconstrictors
      and vasodilators occur in arterial and venous segments of the sheep isolated
      pulmonary vasculature. Such specialization may have important implications for
      the regulation of resistance in this low tone vascular bed.

PMID- 9179386
TI  - Specific Gq protein involvement in muscarinic M3 receptor-induced
      phosphatidylinositol hydrolysis and Ca2+ release in mouse duodenal myocytes.
AB  - 1. Cytosolic Ca2+ concentration ([Ca2+]i) during exposure to acetylcholine or
      caffeine was measured in mouse duodenal myocytes loaded with fura-2.
      Acetylcholine evoked a transient increase in [Ca2+]i followed by a sustained rise
      which was rapidly terminated after drug removal. Although L-type Ca2+ currents
      participated in the global Ca2+ response induced by acetylcholine, the initial
      peak in [Ca2+]i was mainly due to release of Ca2+ from intracellular stores. 2.
      Atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, a muscarinic M3
      antagonist), pirenzepine (a muscarinic M1 antagonist), methoctramine and
      gallamine (muscarinic M2 antagonists) inhibited the acetylcholine-induced Ca2+
      release, with a high affinity for 4-DAMP and atropine and a low affinity for the
      other antagonists. Selective protection of muscarinic M2 receptors with
      methoctramine during 4-DAMP mustard alkylation of muscarinic M3 receptors
      provided no evidence for muscarinic M2 receptor-activated [Ca2+]i increase. 3.
      Acetylcholine-induced Ca2+ release was blocked by intracellular dialysis with a
      patch pipette containing either heparin or an anti-phosphatidylinositol antibody
      and by external application of U73122 (a phospholipase C inhibitor). 4.
      Acetylcholine-induced Ca2+ release was insensitive to external pretreatment with
      pertussis toxin, but concentration-dependently inhibited by intracellular
      dialysis with a patch pipette solution containing an anti-alpha q/alpha 11
      antibody. An antisense oligonucleotide approach revealed that only the Gq protein
      was involved in acetylcholine-induced Ca2+ release. 5. Intracellular applications
      of either an anti-beta com antibody or a peptide corresponding to the G beta
      gamma binding domain of the beta-adrenoceptor kinase 1 had no effect on
      acetylcholine-induced Ca2+ release. 6. Our results show that, in mouse duodenal
      myocytes, acetylcholine-induced release of Ca2+ from intracellular stores is
      mediated through activation of muscarinic M3 receptors which couple with a Gq
      protein to activate a phosphatidylinositol-specific phospholipase C.

PMID- 9179387
TI  - Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by three
      selective type-4 phosphodiesterase inhibitors: in vitro and in vivo studies.
AB  - 1. Previous studies in our laboratory have shown that the synthetic xanthine
      analogue denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is
      a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given
      orally or intraperitoneally (i.p.) to adult male rats. This paper describes the
      results of experiments in which well established in vivo and in vitro methods
      were used to compare the effects of denbufylline on HPA function with those of
      two other selective PDE-4 inhibitors, rolipram and BRL 61063 (1,3
      dicyclopropylmethyl-8-amino-xanthine). For comparison, parallel measurements of
      the immunoreactive- (ir-) luteinising hormone (LH) were made where appropriate.
      2. When injected intraperitoneally, rolipram (40 and 200 micrograms kg-1, P <
      0.005), denbufylline (0.07-0.6 microgram kg-1, P < 0.05) and BRL 61063 (30
      micrograms kg-1, P < 0.005) each produced marked rises in the serum ir
      corticosterone concentrations. However, lower doses of rolipram (1.6 and 8
      micrograms kg-1) and BRL 61063 (0.25-6 micrograms kg-1) were without effect (P >
      0.05). By contrast, intracerebroventricular (i.c.v.) injection of rolipram (8 ng
      1 micrograms kg-1) or denbufylline (50 ng-1 microgram kg-1) failed to influence
      the serum ir-corticosterone concentration. BRL 61063 (8-120 ng kg-1, i.c.v.) was
      also ineffective in this regard although at a higher dose (1 microgram kg-1,
      i.c.v.) it produced a small but significant (P < 0.05) increase in ir
      corticosterone release. Denbufylline also increased the serum ir-LH concentration
      when given peripherally (0.2-0.6 microgram kg-1, i.p., P < 0.05) or centrally
      (100 ng kg-1, i.c.v., P < 0.05) but rolipram (1.6-200 micrograms kg-1, i.p. or 8
      ng-1 microgram kg-1, i.c.v.) and BRL 61063 (0.25-30 micrograms kg-1, i.p. or 1 ng
      1 microgram kg-1, i.c.v.) did not (P > 0.05). 3. In vitro rolipram (10 microM, P
      < 0.01), denbufylline (1 mM, P < 0.001) and BRL 61063 (1 and 10 microM, P < 0.05)
      stimulated the release of corticotrophin releasing hormone (ir-CRH-41) but lower
      concentrations of the drugs were without effect as also was BRL 61063 at 100
      microM (P > 0.05); the rank order of potency was thus BRL 61063 > rolipram >
      denbufylline. The adenylyl cyclase activator forskolin (100 microM, P < 0.01)
      also stimulated the release of ir-CRH-41, producing effects which were additive
      with those of rolipram and denbufylline but not with those of BRL 61063. The
      secretory responses to forskolin (100 microM) were accompanied by a highly
      significant increase in the cyclic AMP content of the hypothalamic tissue (P <
      0.005). Rolipram (10 microM) also significantly (P < 0.05) elevated the
      hypothalamic cyclic AMP but denbufylline (10 mM) and BRL 61063 (10 microM) did
      not. However, all three PDE-inhibitors potentiated the rise in cyclic AMP induced
      by forskolin (P < 0.05). None of the drugs tested, alone or in combination,
      modified the release of arginine vasopressin (ir-AVP) from the hypothalamus. 4.
      Rolipram (100 microM), denbufylline (100 microM) and BRL 61063 (100 microM)
      stimulated the release of corticotrophin (ir-ACTH) from pituitary tissue in vitro
      (P < 0.05) but in lower concentrations they were without significant effect. In
      addition, rolipram (10 microM, P < 0.05), denbufylline (0.1 microM, P < 0.05) and
      BRL 61063 (10 microM, P < 0.05) potentiated the significant (P < 0.05) rises in
      ir-ACTH secretion induced by forskolin (100 microM). Forskolin (100 microM) also
      produced a highly significant increase (P < 0.01) in the tissue cyclic AMP
      content which was further potentiated by rolipram (10 microM), denbufylline (10
      microM) and BRL 61063 (10 microM) which, alone did not affect the cyclic AMP
      content of the tissue. 5. Since both denbufylline and BRL 61063 possess
      significant adenosine A1 receptor blocking activity, further studies examined the
      potential influence of these receptors on the secretion in vitro of CRH-41, AVP
      and ACTH. The release of ir-CRH-41 was increased significantly by adenosine
      deaminase (ADA, 5microml-1, P<0.05) and the A1-receptor antagonist, 1,3
      dicyclopropyl-8-cyclopentylxanthine (DPCPX, 0.1-10nM, P<0.05). The responses to
      ADA were abolished by the A1 receptor agonist N6-cyclo-hexyladenosine (CHA,
      100nM, P<0.05) which alone had no significant effect on ir-CRH-41 release. ADA
      (0.1-10microml-1) and DPCPX (1nM) had weak stimulant and inhibitory effects,
      respectively, on the release of ir-ACTH from the pituitary gland while CHA (0.1
      10nM) was without effect. Ligand binding studies with [3H]-DPCPX as a probe
      demonstrated the presence of specific high affinity A1 binding sites in the
      hypothalamus (Kd=0.7nM; Bmax=367+/-32fmolmg-1 protein) and in the hippocampus
      (Kd=1nM; Bmax=1165 +/-145fmolmg-1 protein). In both tissues binding of the ligand
      was displaced by CHA (IC50=1nM (hypothalamus) and 2nM (hippocampus)), BRL 61063
      (IC50=80nM (hypothalamus) and 100nM (hippocampus)) and denbufylline (IC50=5microM
      (hypothalamus) and 9microM(hippocampus)) but not by rolipram. 6.The results
      suggest that rolipram, denblufylline and BRL 61063 stimulate the HPA axis in the
      rat, acting at the levels of both the hypothalamus and the pituitary gland. Their
      actions may be explained, at least in part, by inhibition of PDE-4 but additional
      actions including blockade of hypothalamic adenosine A1 receptors by denbufylline
      and BRL 61063 cannot be excluded.

PMID- 9179388
TI  - Effects of the non-peptide B2 antagonist FR173657 on kinin-induced smooth muscle
      contraction and relaxation, vasoconstriction and prostaglandin release.
AB  - 1. The non-peptide bradykinin (BK) antagonist (E)-3-(6-acetamido-3-pyridyl)-N-[N
      [2,4-dichloro-3-[(2-methyl-8-quinolin yl) oxymethyl]phenyl]-N
      methylaminocarbonylmethyl]acrylamide (FR173657) was tested in intestinal,
      uterine, tracheal and vascular in vitro preparations. The investigation aimed at
      determining the antagonistic potency, duration of action, specificity for BK
      receptors and apparent mode of antagonistic action of FR173657. 2. Contractions
      of the isolated ileum of the guinea-pig in response to BK were inhibited by
      FR173657 (10-300 nM) in a concentration-dependent manner. The inhibition lasted
      for up to 90 min after wash-out of FR173657. Cumulative concentration-response
      curves to BK were shifted to the right with a concomitant decrease in the maximum
      effect. A pKB value of 8.7 was determined. FR173657 had no effect on contractions
      induced by acetylcholine, histamine, 5-hydroxytryptamine, substance P,
      angiotensin II or caerulein. 3. The concentration-response curves for B2 receptor
      mediated relaxations of the rat isolated duodenum induced by BK were shifted to
      the right together with a concomitant reduction of the maximum BK effect in the
      presence of FR173657 (10-300 nM). A pKB of 9.0 +/- 0.2 was calculated. FR173657
      had no effect on B1 receptor-mediated relaxations in response to des-Arg9-BK. 4.
      The concentration-response curves for BK-induced contractions of the rat isolated
      uterus were shifted to the right by FR173657 (3-300 nM) in a concentration
      dependent and parallel manner. The Schild plot for the inhibition caused by
      FR173657 had a slope of -0.98 indicating a competitive mode of antagonism. A pA2
      value of 9.1 was determined. 5. Contractions of the circular smooth muscles of
      the guinea-pig isolated trachea in response to BK were concentration-dependently
      inhibited by FR173657 (10-100 nM). An affinity estimate of 9.3 was calculated for
      FR173657. Contractions induced by acetylcholine and relaxations in response to
      isoprenaline remained completely unaffected by FR173657. 6. In the rabbit
      isolated perfused ear, BK (0.01-10 nmol) produced a dose-dependent
      vasoconstriction. In the presence of 30 nM FR173657, the effects of BK were
      reduced by at least 60%, while FR173657 completely abolished the effects of all
      BK doses at 300 nM. FR173657 did not affect vasoconstriction induced by
      noradrenaline or angiotensin II. 7. The arterial injection of BK (10 nmol) into
      the rabbit isolated perfused ear caused an approximately three fold increase in
      the release of the prostaglandins E2 and I2 into the venous effluent. The BK
      stimulated prostaglandin release was completely abolished in the presence of
      FR173657 (300 nM) while the basal prostaglandin release was unchanged. 8. In
      summary, FR173657 was shown to be a highly potent and selective BK antagonist
      which was active on B2, but not B1, receptors. FR173657 was a competitive
      antagonist in the rat uterus but showed a deviation from competitive inhibition
      in the other preparations studied similar to other second generation peptide
      antagonists. The inhibitory action in vitro was long-lasting, but was fully
      reversible.

PMID- 9179389
TI  - Effects of delayed treatment with nebracetam on neurotransmitters in brain
      regions after microsphere embolism in rats.
AB  - 1. The effects of delayed treatment with nebracetam, a novel nootropic drug, on
      neurotransmitters of brain regions were examined in rats with microsphere
      embolism-induced cerebral ischaemia. 2. Cerebral ischaemia was induced by
      administration of 900 microspheres (48 microns) into the internal carotid artery.
      The rats with stroke-like symptoms were treated p.o. with 30 mg kg-1 nebracetam
      twice daily. The levels of acetylcholine, dopamine, noradrenaline, 5
      hydroxytryptamine (5-HT) and their metabolites in the cerebral cortex, striatum
      and hippocampus of animals with microsphere embolism were determined by high
      performance liquid chromatography (h.p.l.c.) on the 3rd and 7th days after the
      operation. 3. Although the microsphere embolism induced significant changes in
      most of the neurotransmitters and some of their metabolites in the brain regions,
      the delayed treatment with nebracetam partially restored only the hippocampal 5
      HT and the striatal dopamine metabolite contents on the 3rd day. 4. The
      hippocampal in vivo 5-HT synthesis, but not the striatal dopamine synthesis, was
      attenuated in rats with microsphere embolism on the 3rd day, but was restored by
      treatment with nebracetam. In vivo striatal dopamine turnover rate of the rats
      with microsphere embolism was inhibited on the 3rd day irrespective of treatment
      with nebracetam. 5. The present study provides evidence for a possible action of
      nebracetam on 5-HT metabolism in the ischaemic brain.

PMID- 9179390
TI  - Characterization of the vasodilator properties of peroxynitrite on rat pulmonary
      artery: role of poly (adenosine 5'-diphosphoribose) synthase.
AB  - 1. The pulmonary vasculature is constantly exposed to oxygen and reactive oxygen
      species such as nitric oxide (NO) and superoxide anions which can combine at a
      near diffusion limited rate, to form the powerful, oxidant, peroxynitrite (ONOO
      ). When formed in large amounts, ONOO- is thought to contribute to tissue injury
      and vascular dysfunction seen in diseases such as the acute respiratory distress
      syndrome (ARDS) and septic shock. Recent studies have shown that ONOO- can cause
      vasodilatation and at higher concentrations can activate poly (adenosine 5'
      diphosphoribose) synthase (PARS) leading to consumption of nicotinamide adenine
      dinucleotide (NAD+) and adenosine 5'-triphosphate (ATP). As the lung represents a
      prime site for ONOO- formation, we characterized its effects on pulmonary
      vascular tone and on endothelial function. In addition, we have assessed the role
      of PARS in producing the vasoactive properties of ONOO- on pulmonary artery
      rings. 2. Isolated pulmonary artery rings from rats were mounted in organ baths
      containing warmed and gassed (95% O2: 5% CO2) Krebs buffer. Force was measured
      with isometric force transducers. After equilibration, ONOO- (10 nM-100 microM)
      was added in a cumulative manner. In separate experiments designed to assess any
      vasodilator properties of ONOO-, tissues were pre-contracted with the thromboxane
      mimetic U46619 (1 microM). Once a stable base-line was achieved, ONOO- was added
      in a cumulative fashion. ONOO- had no significant effect on resting pulmonary
      artery tone but caused concentration-dependent relaxations of pre-contracted
      vessels in the range 1 microM to 100 microM. In some experiments the effects of
      freshly prepared ONOO- solutions were compared with those allowed to decay at 4
      degrees C for 2 days. 3. In some experiments either vehicle or ONOO- (1, 10 or
      100 microM) was added for 15 min before U46619 (1 microM). Concentration-response
      curves to the endothelium-dependent vasodilator, acetylcholine (10 nM-100 microM)
      were then constructed. In these experiments, ONOO- (1 microM or 10 microM) had no
      effect on the actions of acetylcholine. However, at the highest concentration
      tested (100 microM), ONOO- increased acetylcholine-induced relaxations. 4. The
      vasodilator actions of ONOO- were unaffected by the NO synthase inhibitor, NG
      nitro-L-arginine methyl ester (L-NAME; 100 microM) or by removal of superoxide
      anions with superoxide dismutase (SOD) (30 units ml-1). However, the relaxations
      induced by ONOO- were significantly inhibited by the PARS inhibitor, 3
      aminobenzamide (10 microM). In contrast to its effects on ONOO-, 3-aminobenzamide
      had no effect on the relaxation caused by acetylcholine or sodium nitrite, but
      actually increased that induced by sodium nitroprusside. 5. These data show that
      ONOO- causes vasodilatation of rat pulmonary arteries, probably via activation of
      PARS. Moreover, at concentrations where relaxation was achieved, ONOO- did not
      affect the ability of pulmonary artery rings to relax to acetylcholine. We
      propose that ONOO-, but not endothelially derived NO, activates PARS resulting in
      the rapid depletion of ATP and a consequent reduction in contraction as well as
      other active processes of vascular smooth muscle. The finding that 3
      aminobenzamide inhibited the actions of ONOO- but not acetylcholine, suggests
      that NO and ONOO- cause relaxation by independent mechanisms. It has been
      suggested that ONOO- is responsible for the vascular hyporesponsiveness to
      constrictor agents seen in experimental sepsis. This observation together with
      our current finding, that 3-aminobenzamide inhibits the relaxation induced by
      ONOO- but not by acetylcholine, suggests that inhibitors of PARS may reduce the
      persistent hypotension seen in sepsis without affecting the actions of
      endothelium-derived NO. Thus, the use of PARS inhibitors may represent a novel
      therapeutic approach to the treatment of septic shock.

PMID- 9179391
TI  - The effect of continuous versus intermittent treatment with transdermal
      nitroglycerin on pacing-induced preconditioning in conscious rabbits.
AB  - 1. Tolerance to the hypotensive effect of nitroglycerin (NG) blocks
      preconditioning induced by rapid ventricular pacing (RVP) in rabbits. In the
      present work the effect of continuous versus intermittent treatment with
      transdermal nitroglycerin on the pacing-induced preconditioning phenomenon was
      studied in conscious rabbits. 2. RVP (500 beats min-1 over 5 min) increased left
      ventricular end-diastolic pressure (LVEDP) from baseline 4.1 +/- 0.9 to
      postpacing 13.8 +/- 2.9 mmHg (P < 0.001) with a right intraventricular ST-segment
      elevation of 1.25 +/- 0.13 mV, two indicators of myocardial ischaemia. These
      changes were significantly attenuated when the RVP period was preceded by a
      preconditioning pacing of the same rate and duration with an interpacing interval
      of 5 min. 3. Protection by preconditioning was abolished when the animals had
      been made tolerant to the vasodilator effect of 30 micrograms kg-1 NG by the
      application of transdermal NG (approx. 0.07 mg kg-1 h-1) over 7 days.
      Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment
      elevation and LVEDP-increase over the 7 day period. 4. With intermittent
      transdermal NG treatment (12 h 'patch on' vs 'patch off'), neither development of
      vascular tolerance nor attenuation of the NG- or preconditioning-induced anti
      ischaemic effects were observed. However, the severity of pacing-induced
      myocardial ischaemia was significantly increased during the 'patch off' periods.
      5. In a second set of experiments, postpacing changes in cardiac cyclic GMP and
      cyclic AMP levels were determined by means of radioimmunoassay in chronically
      instrumented anaesthetized open-chest rabbits with the same NG-treatment
      protocols. Preconditioning reduced postpacing increase in cyclic AMP with an
      increase in cyclic GMP concentrations in hearts of the untreated animals and in
      those given patches intermittently during both 'patch on' and 'patch off'
      periods. However, the preconditioning effect on either cyclic nucleotide was
      blocked in the tolerant animals. 6. Transdermal NG increased resting levels of
      both cardiac cyclic nucleotides in the non-tolerant but not in the tolerant
      state. The postpacing increase in cyclic AMP content was inhibited by transdermal
      NG, independent of vascular tolerance development, whereas an cyclic GMP content
      was exclusively seen in the non-tolerant animals. 7. We conclude that the anti
      ischaemic effect of NG is independent of the cyclic GMP mechanism in the tolerant
      state. While intermittent NG therapy prevents development of vascular tolerance
      and preserves preconditioning, the nitrate-free periods yield an increased
      susceptibility of the heart to ischaemic challenges.

PMID- 9179392
TI  - The effect of the neuropeptide substance P on desensitization of ATP receptors of
      PC12 cells.
AB  - 1. Patch clamp recording (whole cell configuration) was employed to investigate
      the modulatory action of substance P on inward currents elicited by adenosine 5'
      triphosphate (ATP, focally applied via a pressure pipette) from phaechromocytoma
      (PC12) cells usually held at -70 mV. 2. Bath-applied substance P (0.2-20 microM)
      had no effect on baseline membrane current but reversibly reduced ATP peak
      currents in a concentration-dependent fashion. The depressant effect was not
      associated with a change in the ATP current reversal potential. 3. Equiamplitude
      peak responses induced by 50 microM or 5 mM ATP were differentially affected by
      substance P which preferentially reduced currents evoked by 5 mM ATP. In the
      presence of substance P a conditioning pulse of ATP evoked a stronger depression
      to subsequent test pulses of the same agonist. 4. Combined patch clamping and
      confocal laser imaging of intracellular Ca2+ ([Ca2+]i) of single PC12 cells
      showed that substance P (applied by a pressure pipette) per se had no effect on
      [Ca2+]i or current baseline, although it reduced the inward current and
      associated [Ca2+]i rise elicited by ATP. 5. These results are interpreted as due
      to facilitation by substance P of desensitization of ATP-gated P2x2 receptors of
      PC12 cells. It is proposed that the novel modulation by this peptide of ATP
      responses may serve as a model for further studies aimed at elucidating the
      action of substance P on purinergic neurotransmission.

PMID- 9179393
TI  - Cardiovascular effects of a low-dose combination of ramipril and felodipine in
      spontaneously hypertensive rats.
AB  - 1. Cardiovascular effects of submaximal antihypertensive doses of the angiotensin
      converting enzyme inhibitor, ramipril (0.25 mg kg-1 day-1 in the food), and the
      calcium channel blocker, felodipine (0.4 mg kg-1 day-1 subcutaneously by osmotic
      minipump), both alone and in combination, were examined in spontaneously
      hypertensive rats (SHR) in a four-week study. 2. Both ramipril and felodipine as
      monotherapy decreased systolic blood pressure. The antihypertensive effect of the
      drug combination was more than that of ramipril treatment alone, but not
      significantly better than that of felodipine monotherapy. Ramipril or felodipine
      treatments did not significantly affect the heart rate, either alone or in
      combination. 3. The beneficial effect of ramipril monotherapy on left ventricular
      hypertrophy was more prominent than that of felodipine. The cardioprotective
      effect of felodipine was improved when combined to ramipril. The systolic blood
      pressure at the end of the experimental period correlated only weakly with left
      ventricular hypertrophy. 4. Responses of mesenteric arterial rings in vitro were
      examined at the end of the four-week study. Ramipril and felodipine monotherapies
      as well as their combination markedly improved the endothelium-dependent vascular
      relaxation responses to acetylcholine. The combination of ramipril and felodipine
      slightly enhanced the endothelium-independent vascular relaxation responses to
      sodium nitroprusside. Ramipril treatment alone slightly diminished the vascular
      contractile responses to noradrenaline. Neither ramipril nor felodipine alone or
      in combination affected the vascular contractile responses to potassium chloride.
      5. Ramipril treatment, both alone and in combination with felodipine, caused a
      three fold increase in plasma renin activity. Serum aldosterone, fasting blood
      glucose level, serum insulin and the 24 hour urinary excretions of sodium,
      potassium, magnesium, calcium, phosphorus or protein were not significantly
      affected by the drug treatments. 6. Our findings suggest that a better overall
      control of hypertension and end-organ damages, without an increase in adverse
      effects, can be achieved by the combination of submaximal antihypertensive doses
      of felodipine and ramipril than by monotherapy with either drug alone.

PMID- 9179394
TI  - Attenuation of precipitated morphine withdrawal symptoms by acute i.c.v.
      administration of a group II mGluR agonist.
AB  - 1. We previously showed that chronic i.c.v. antagonism of metabotropic glutamate
      receptors (mGluRs) concurrently with s.c. morphine significantly attenuated
      precipitated withdrawal symptoms. Conversely, acute i.c.v. injection of a
      selective group II mGluR antagonist just before the precipitation of withdrawal
      exacerbated abstinence symptoms. 2. In the present study, we showed that acute
      i.c.v. administration of the non-selective mGluR agonist 1-aminocyclopentane-1,3
      dicarboxylic acid ((1S,3R)-ACPD), as well as the group II selective agonist
      (2S,1'R,2'R,3'R)-2-(2'.3'-dicarboxycyclopropyl)glycine (DCG-IV), significantly
      attenuated the severity of precipitated withdrawal symptoms. 3. From these
      results we hypothesize that chronic opioid treatment may indirectly induce a
      desensitization of group II mGluRs, which contributes to the development of
      dependence.

PMID- 9179395
TI  - The atypical antipsychotic profile of NRA0045, a novel dopamine D4 and 5
      hydroxytryptamine2A receptor antagonist, in rats.
AB  - 1. The atypical antipsychotic profile of (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1
      [4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045), a potent
      dopamine D4 and 5-hydroxytryptamine (5-HT)2A receptor antagonist, was examined in
      rats. 2. Spontaneous locomotor activity was decreased dose-dependently with i.p.
      administration of clozapine (ED50 3.7 mg kg-1), haloperidol (ED50 0.1 mg kg-1)
      and chlorpromazine (ED50 0.9 mg kg-1), whereas inhibition of this type of
      behaviour induced by i.p. administration of NRA0045, at doses up to 10 mg kg-1,
      did not exceed 50%. 3. Locomotor hyperactivity induced by methamphetamine (MAP, 2
      mg kg-1, i.p.) in rats (a model of antipsychotic activity) was dose-dependently
      antagonized by NRA0045 (ED50 0.4 mg kg-1, i.p., and 0.3 mg kg-1, p.o.,
      respectively), clozapine (ED50 0.3 mg kg-1, i.p. and 0.8 mg kg-1, p.o.,
      respectively), haloperidol (ED50 0.02 mg kg-1, i.p. and 0.1 mg kg-1, p.o.,
      respectively), chlorpromazine (ED50 0.3 mg kg-1, i.p. and 3.3 mg kg-1, p.o.,
      respectively). In contrast, the MAP (3 mg kg-1, i.v.)-induced stereotyped
      behaviour in rats (a model of extrapyramidal symptoms) was not affected by
      NRA0045 or clozapine, at the highest dose given (30 mg kg-1, i.p.). Haloperidol
      (ED50 0.3 mg kg-1, i.p.) and chlorpromazine (ED50 4.8 mg kg-1, i.p.) strongly
      blocked the MAP-induced stereotyped behaviour. NRA0045 and clozapine selectively
      blocked behaviour associated with activation of the mesolimbic/mesocortical
      dopamine neurones rather than nigrostriatal dopamine neurones. 4. Extracellular
      single-unit recording studies demonstrated that MAP (1 mg kg-1, i.v.) decreased
      the firing rate in the substantia nigra (A9) and ventral tegmental area (A10)
      dopamine neurones in anaesthetized rats. NRA0045 completely reversed the
      inhibitory effects of MAP on A10 dopamine neurones (ED50 0.1 mg kg-1, i.v.),
      whereas the inhibitory effects of MAP on A9 dopamine neurones were not affected
      by NRA0045, in doses up to 1 mg kg-1 (i.v.). Clozapine completely reversed the
      inhibitory effects of MAP on A10 dopamine neurones (ED50 1.9 mg kg-1, i.v.) and
      on A9 dopamine neurones (ED50 2.5 mg kg-1, i.v.). Haloperidol completely reversed
      the inhibitory effects of MAP on A10 (ED50 0.03 mg kg-1, i.v.) and on A9 dopamine
      neurones (0.02 mg kg-1, i.v.). NRA0045, like clozapine, was more potent in
      reversing the effects of MAP on A10 than A9 dopamine neurones. 5. Prepulse
      inhibition (PPI) is impaired markedly in humans with schizophrenia. The
      disruption of PPI in rats by apomorphine (0.5 mg kg-1, s.c.) was reversed
      significantly by NRA0045 (3 mg kg-1, i.p.), clozapine (3 mg kg-1, i.p.) and
      haloperidol (0.3 mg kg-1, i.p.). 6. Phencyclidine (PCP) elicits predominantly
      psychotic symptoms in normal humans and in schizophrenics. NRA0045 (0.03-0.3 mg
      kg-1, i.p.) and clozapine (0.1-1 mg kg-1, i.p.) significantly and dose
      dependently shortened the PCP(1.25 mg kg-1, i.p.)-induced prolonged swimming
      latency in rats in a water maze task, whereas haloperidol (0.01-0.1 mg kg-1,
      i.p.) did not significantly alter swimming latency. 7. These findings suggest
      that NRA0045 may have unique antipsychotic activities without the liability of
      motor side effects typical of classical antipsychotics.

PMID- 9179396
TI  - Effects of trout bradykinin on the motility of the trout stomach and intestine:
      evidence for a receptor distinct from mammalian B1 and B2 subtypes.
AB  - 1. Trout bradykinin ([Arg0, Trp5, Leu8]-bradykinin; trout BK), recently isolated
      from kallikrein-treated trout plasma, produced sustained and concentration
      dependent contractions of isolated longitudinal muscle from rainbow trout stomach
      (pD2 = 7.01 +/- 0.03) and proximal small intestine (pD2 = 7.37 +/- 0.07). The
      maximum responses were 85 +/- 2% (stomach) and 101 +/- 35% (intestine) of the
      corresponding responses to 10(-5) M acetylcholine. Strips of circular smooth
      muscle from trout stomach and intestine did not contract in response to trout BK.
      2. The potency of trout BK on gastric smooth muscle motility was significantly (5
      fold; P < 0.01) reduced in the presence of the cyclo-oxygenase inhibitor,
      indomethacin (10(-5) M) and by 4 fold (P < 0.05) in the presence of the
      lipoxygenase inhibitor, MK-886 (10(-6) M), but there was no effect on the maximum
      response. Potency was also significantly reduced in the presence of 10(-6) M
      methysergide (3 fold; P < 0.02) and 10(-6) M tetrodotoxin (2 fold, P < 0.05) but
      atropine was without effect. 3. [Tyr0, Trp5, Leu8]-BK was a full agonist but was
      approximately 50 fold less potent (pD2 = 5.35 +/- 0.08) than trout BK, [Arg0,
      Trp5, Leu8]des-Arg9-BK was a partial) agonist (pD2 = 6.80 +/- 0.03; 56 +/- 7% of
      the maximum response to trout BK) but [Trp5, Leu8]-BK, [Trp5,Leu8]-des-Arg9-BK
      and mammalian BK produced no, or only very weak, contractions of the trout
      stomach. 4. The mammalian B1 receptor antagonist, [Leu8]des-Arg9-BK was without
      effect on the response of the trout stomach to trout BK. The potent mammalian B2
      receptor antagonist Hoe 140 was a partial agonist (pD2 = 7.44 +/- 0.12; 57 +/-
      15% of the maximum response to trout BK). 5. We conclude that the effects of
      trout BK on the motility of rainbow trout gastric smooth muscle are mediated
      through interaction with a receptor that has appreciably different ligand-binding
      properties than the mammalian B1 and B2 receptor subtypes. An involvement of
      arachidonic acid metabolites and 5-hydroxytryptaminergic nerves in the mechanism
      of action of the peptide is suggested.

PMID- 9179397
TI  - Effect of englitazone on KATP and calcium-activated non-selective cation channels
      in CRI-G1 insulin-secreting cells.
AB  - 1. The effects of englitazone sodium, an antidiabetic agent, on ion channel
      activity in the CRI-G1 insulin secreting cell line was examined by use of the
      patch clamp technique. 2. Application of englitazone to the outside of CRI-G1
      cells in the whole-cell recording configuration produced concentration-dependent
      inhibition of KATP currents with an IC50 value of 8 microM. The inhibition of the
      K+ current was not affected by the removal of Mg2+ ions from or the addition of
      trypsin to the solution bathing the intracellular surface of the cell membrane.
      3. Englitazone also inhibited KATP channel activity in recordings from inside out
      excise membrane patches. The concentration-dependence of inhibition was identical
      to that observed in whole-cell recordings and was voltage-independent. Single
      channel recordings confirmed that neither the absence or presence of Mg2+ ions
      nor the addition of trypsin at the intracellular surface of the membrane
      influenced the inhibition of KATP channels by englitazone. 4. Englitazone also
      inhibited Ca(2+)-activated non-selective cation (NSCa) channels in inside-out
      patches in a concentration-dependent and voltage-independent manner with an IC50
      value of 10 microM. In comparison, the non-sulphonylurea KATP channel blocker
      ciclazindol produced a slight voltage-dependent inhibition of the NSCa channel at
      a concentration of 20 microM. 5. In whole-cell recordings englitazone, at a
      relatively high concentration (50 microM) in comparison with that required to
      block KATP and NSCa channels, inhibited voltage-activated Ca2+ currents by 33%
      but did not inhibit voltage-activated K+ and Na+ currents. 6. It is concluded
      that englitazone is a novel blocker of NSCa and KATP channels. The inhibition of
      KATP channels occurs following procedures that dissociate sulphonylurea receptor
      coupling to the channel. The equipotent and voltage-independent inhibition of
      NSCa and KATP channels by englitazone may indicate a common mechanism of block.

PMID- 9179398
TI  - Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown
      in vitro and in vivo.
AB  - 1. Ro 32-3555 (3(R)-(cyclopentylmethyl)-2(R)-[(3,4,4-trimethyl-2,5-dioxo-1-
      imidazolidinyl)methyl]-4-oxo-4-piperidinobutyrohydroxamic acid) is a potent,
      competitive inhibitor of human collagenases 1, 2 and 3 (Ki values of 3.0, 4.4 and
      3.4 nM, respectively). The compound is a selective inhibitor of collagenases over
      the related human matrix metalloproteinases stromelysin 1, and gelatinases A and
      B (Ki values of 527, 154 and 59 nM, respectively). 2. Ro 32-3555 inhibited
      interleukin-1 alpha (IL-1 alpha)-induced cartilage collagen degradation in vitro
      in bovine nasal cartilage explants (IC50 = 60 nM). 3. Ro 32-3555 was well
      absorbed in rats when administered orally. Systemic exposure was dose related,
      with an oral bioavailability of 26% at a dose of 25 mg kg-1. 4. Ro 32-3555
      prevented granuloma-induced degradation of bovine nasal cartilage cylinders
      implanted subcutaneously into rats (ED50 = 10 mg kg-1, twice daily, p.o.). 5. Ro
      32-3555 dosed once daily for 14 days at 50 mg kg-1, p.o., inhibited degradation
      of articular cartilage in a rat monoarthritis model induced by an intra-articular
      injection of Propionibacterium acnes. 6. Ro 32-3555 is a potential therapy for
      the treatment of the chronic destruction of articulating cartilage in both
      rheumatoid and osteoarthritis.

PMID- 9179399
TI  - Inhibition by mibefradil, a novel calcium channel antagonist, of Ca(2+)- and
      volume-activated Cl- channels in macrovascular endothelial cells.
AB  - 1. We have studied the effects of mibefradil, a novel calcium antagonist, on the
      resting potential and ion channel activity of macrovascular endothelial cells
      (calf pulmonary artery endothelial cells, CPAE). The patch clamp technique was
      used to measure ionic currents and the Fura-II microfluorescence technique to
      monitor changes in the intracellular Ca2+ concentration, [Ca2+]i. 2. Mibefradil
      (10 microM) hyperpolarized the membrane potential of CPAE cells from its mean
      control value of -26.6 +/- 0.6 mV (n = 7) to -59.8 +/- 1.7 mV (n = 6). A
      depolarizing effect was observed at higher concentrations (-13.7 +/- 0.6 mV, n =
      4, 30 microM mibefradil). 3. Mibefradil inhibited Ca(2+)-activated Cl- currents,
      ICl,Ca, activated by loading CPAE cells via the patch pipette with 500 nM free
      Ca2+ (Ki = 4.7 +/- 0.18 microM, n = 8). 4. Mibefradil also inhibited volume
      sensitive Cl- currents, ICl,vol, activated by challenging CPAE cells with a 27%
      hypotonic solution (Ki = 5.4 +/- 0.22 microM, n = 6). 5. The inwardly rectifying
      K+ channel, IRK, was not affected by mibefradil at concentrations up to 30
      microM. 6. Ca2+ entry activated by store depletion, as assessed by the rate of
      [Ca2+]i-increase upon reapplication of 10 mM extracellular Ca2+ to store-depleted
      cells, was inhibited by 17.6 +/- 6.5% (n = 8) in the presence of 10 microM
      mibefradil. 7. Mibefradil inhibited proliferation of CPAE cells. Half-maximal
      inhibition was found at 1.7 +/- 0.12 microM (n = 3), which is similar to the
      concentration for half-maximal block of Cl- channels. 8. These actions of
      mibefradil on Cl- channels and the concomitant changes in resting potential
      might, in addition to its effect on T-type Ca2+ channels, be an important target
      for modulation of cardiovascular function under normal and pathological
      conditions.

PMID- 9179400
TI  - Examination of the role of endopeptidase 3.4.24.15 in A beta secretion by human
      transfected cells.
AB  - 1. We have taken advantage of our recent development of highly potent and
      specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative
      contribution of the enzyme in the secretion of A beta by HK293 transfected cells
      overexpressing the wild type and the Swedish (Sw) double mutated form of beta
      APP751. 2. First, we showed that HK293 cells contain a peptidase activity, the
      inhibition profile of which fully matches that of purified endopeptidase
      3.4.24.15. Second, we established that the treatment of HK293 cells with specific
      phosphinic inhibitors leads to about 80% inhibition of intracellular
      endopeptidase 3.4.24.15 activity, indicating that these inhibitors penetrate the
      cells. 3. Metabolic labelling of wild type and Sw beta APP751-expressing cells,
      followed by immunoprecipitation of A beta-containing peptides, revealed the
      secretion of A beta and the intracellular formation of an A beta-containing 12
      kDa product. 4. A beta secretion by Sw beta APP751 transfected cells was
      drastically enhanced when compared to cells expressing wild type beta APP751.
      This production was not affected by endopeptidase 3.4.24.15 inhibitors in either
      cell type. This correlates well with the observation that endopeptidase 3.4.24.15
      does not cleave recombinant baculoviral Sw beta APP751, in vitro. 5. Our previous
      data indicated that endopeptidase 3.4.24.15 activity was reduced in the parietal
      cortex of Alzheimer's disease affected brains and that the enzyme probably
      participated, in this brain area, to the catabolism of somatostatin 1-14.
      However, the present work indicates that endopeptidase 3.4.24.15 does not seem to
      behave as a beta-secretase in HK293 transfected cells. Therefore, it is suggested
      that endopeptidase 3.4.24.15 could participate in the symptomatology, but
      probably not in the aetiology of Alzheimer's disease.

PMID- 9179401
TI  - Role of 5-ht7 receptors in the long-lasting hypotensive response induced by 5
      hydroxytryptamine in the rat.
AB  - 1. The receptor mediating the long-lasting hypotensive effect of intravenous
      (i.v.) 5-hydroxytryptamine (5-HT) in the rat was originally classified as 5-HT1
      like. Since some pharmacological properties of this receptor are closely similar
      to those for the cloned 5-ht7 receptor, the present study investigated the
      effects of several 5-HT receptor agonists and antagonists showing high affinity
      for the cloned 5-ht7 receptor in pithed rats with artificially raised blood
      pressure. 2. I.v. bolus administration of 5-HT, 5-carboxamidotryptamine (5-CT), 5
      methoxytryptamine, lisuride and sumatriptan to bilaterally vagotomized pithed
      rats pretreated with ketanserin (0.18 mumol kg-1, i.v.), the diastolic blood
      pressure of which had been raised by a continuous i.v. infusion of methoxamine
      (60-80 nmol kg-1 min-1), produced dose-dependent hypotensive responses; only 5-HT
      and 5-CT displayed similar maximum effects. In addition to mimicking the
      hypotensive action of 5-HT with a lower maximum effect, lisuride strongly
      antagonized the 5-CT-induced hypotensive responses thus suggesting a partial
      agonist effect. The rank order of hypotensive agonist potency was 5-CT > > 5-HT >
      or = 5-methoxytryptamine > or = lisuride > > sumatriptan. 3. In experiments with
      antagonists, i.v. treatment with metergoline (2.48 mumol kg-1), mesulergine (2.76
      mumol kg-1), methysergide (2.13 mumol kg-1), lisuride (0.22 mumol kg-1),
      methiothepin (0.68 mumol kg-1), mianserin (10.6 mumol kg-1), or the atypical
      antipsychotic drugs, clozapine (11.0 mumol kg-1) or risperidone (78.0 nmol kg-1),
      produced significant rightward displacements of the dose-response curve for 5-CT
      in methoxamine-infused pithed animals pretreated with ketanserin (0.18 mumol kg
      1, i.v.); lisuride, methiothepin and risperidone behaved as non-competitive
      antagonists as they elicited a significant reduction of the maximum effect to 5
      CT. In contrast, blockade of 5-HT1, 5-HT3 and 5-HT4 receptors with i.v.
      propranolol (3.38 mumol kg-1), MDL-72222 (1.59 mumol kg-1) and GR125487 (1.91
      mumol kg-1), respectively, did not alter 5-CT-induced hypotensive responses;
      ketanserin (0.18 mumol kg-1, i.v.) failed to modify the dose-response curve for 5
      CT in saline-pretreated animals. Lastly, inhibition of the prostaglandin-forming
      cyclo-oxygenase and nitric oxide synthase with indomethacin (14 mumol kg-1, i.v.)
      and NG-nitro-L-arginine methyl ester (L-NAME, 120 mumol kg-1, i.v.),
      respectively, had no significant effects on 5-CT-induced hypotensive effects. 4.
      Taken together, the present pharmacological data suggest that the long-lasting
      vasodepressor action of 5-HT in the rat involves activation of receptors closely
      similar to the cloned 5-ht7 subtype. Since no evidence for an indirect mechanism
      could be obtained, these receptors may be primarily located in the vascular
      smooth muscle of the systemic resistance vessels. These findings represent
      further evidence favouring the functional role of the 5-ht7 receptor.

PMID- 9179402
TI  - Pharmacological properties of non-adrenergic, non-cholinergic inhibitory
      transmission in chicken gizzard.
AB  - 1. Non-adrenergic, non-cholinergic (NANC) inhibitory transmission in chicken
      gizzard was studied by use of intracellular microelectrode techniques. Changes in
      membrane potential in response to NANC nerve stimulation were recorded in the
      gizzard smooth muscle pretreated with atropine (1 microM) and guanethidine (1
      microM). 2. Field stimulation of the intramural nerves (FS) evoked inhibitory
      junction potentials (i.j.ps) which were abolished by tetrodotoxin (1 microM), but
      not inhibited at all by K+ channel blockers including apamin (0.5 microM),
      tetraethylammonium (TEA, 10 mM), charybdotoxin (0.2 microM) and glibenclamide (10
      microM). 3. NG-nitro-L-arginine (3 mM), an inhibitor of nitric oxide (NO)
      synthase, inhibited i.j.ps. The effect was reversed by L-arginine (3 mM), but not
      by D-arginine (3 mM). 4. 8-Bromo cyclic GMP (100 microM), a membrane permeable
      analogue of cyclic GMP, produced a membrane hyperpolarization which was blocked
      by TEA (10 mM) or glibenclamide (10 microM). 5. NO at concentrations of up to 400
      microM affected neither i.j.ps nor resting membrane potential. On the other hand,
      NO (80 microM) caused the membrane to hyperpolarize in the smooth muscle of
      guinea-pig ileum. 6. These results suggest that in the chicken gizzard, NANC
      i.j.ps may not arise from opening of conventional types of K+ channel and that NO
      seems unlikely to be involved in the generation of i.j.ps. A possible mechanism
      by which the inhibitory effect of NG-nitro-L-arginine on i.j.ps was brought about
      will be discussed.

PMID- 9179403
TI  - Effect of interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma
      on the induction of cyclo-oxygenase-2 in cultured human airway smooth muscle
      cells.
AB  - 1. Increased levels of several pro-inflammatory cytokines including interleukin-1
      beta (IL-1 beta) and tumour necrosis factor-alpha (TNF alpha) have been found in
      bronchoalveolar lavage fluid from symptomatic asthmatic patients. IL-1 beta, TNF
      alpha and interferon-gamma (IFN gamma) are known to stimulate a number of cells
      to produce inflammatory mediators such as prostaglandins. Although airway smooth
      muscle (ASM) is known to be a rich source of prostaglandins, the regulation of
      cyclo-oxygenase (COX) isoforms and prostanoid production by proinflammatory
      cytokines have not been studied in human airway smooth muscle. 2. We studied the
      effects of IL-1 beta, TNF alpha and IFN gamma on the induction of two isoforms of
      cyclo-oxygenase and its relation to prostaglandin E2 (PGE2) release and COX
      activity (reflected by PGE2 synthesis from exogenous arachidonic acid) in human
      cultured airway smooth muscle cells. 3. IL-1 beta, but not TNF alpha or IFN
      gamma, caused a time- and concentration-dependent enhancement in PGE2 and other
      prostanoid (6-keto-PGF1 alpha, PGF2 alpha, thromboxane B2 (TXB2) and PGD2)
      production, with PGE2 and 6-keto-PGF1 alpha as the principal products. This
      stimulation was accompanied by a corresponding increase in COX activity. 4. COX-2
      protein measured by Western blot analysis was not detectable in untreated cells,
      but was increased in a time- and concentration-dependent manner by IL-1 beta, but
      not TNF alpha or IFN gamma. In contrast, no variation in the expression of COX-1
      protein was observed. 5. Pretreatment with the conventional non-steroidal anti
      inflammatory drugs (NSAIDs), indomethacin and ibuprofen, and the selective COX-2
      inhibitors, NS-398 and nimesulide, completely blocked IL-1 beta-induced PGE2
      release and COX activity. The glucocorticosteroid dexamethasone and protein
      synthesis inhibitors, cycloheximide and actinomycin D, not only markedly
      inhibited IL-1 beta-stimulated PGE2 release and COX activity but also suppressed
      IL-1 beta-induced COX-2 induction. 6. This study demonstrates that human cultured
      ASM cells release prostanoids in response to IL-1 beta stimulation and that the
      response is mostly mediated by the induction of COX-2 rather than COX-1
      isoenzyme, implying that airway smooth muscle may be an important source of
      prostaglandins in human airways and that COX-2 may play an important role in the
      regulation of the inflammatory process in asthma.

PMID- 9179404
TI  - Comparison of the nitric oxide and cyclo-oxygenase pathway in mesenteric
      resistance vessels of normotensive and spontaneously hypertensive rats.
AB  - 1. The double perfused mesentery was used to compare arterial and venous KCl- and
      acetylcholine (ACh)-induced responses in tissues taken from normotensive (WKY)
      and spontaneously hypertensive rats (SHR) in the presence or absence of
      inhibitors of nitric oxide (NO) synthase (NG-nitro-L-arginine (L-NOARG) and NG
      nitro-L-arginine methyl ester (L-NAME)) and cyclo-oxygenase (indomethacin,
      mefenamic acid). 2. KCl (20 to 120 mM K+) caused concentration-dependent
      increases in arterial and venous perfusion pressures. The maximal arterial
      effects were significantly higher in the SHRs than in the WKY, with no
      differences in the venous pressor responses. 3. L-NAME and L-NOARG (100 microM)
      had no effect on the basal perfusion pressures in tissues from either WKY or
      SHRs, and mefenamic acid only induced a significant reduction of the basal
      perfusion pressures in the venous mesenteric vessels isolated from WKY. 4. L-NAME
      and L-NOARG (100 microM) potentiated the pressor responses to KCl to the same
      extent in the venous and arterial beds derived from WKY and SHR, while
      indomethacin and mefenamic acid (5 microM) only significantly decreased these
      responses in WKY. 5. Acetylcholine (ACh)-induced relaxations (1 nM to 10 microM)
      were significantly higher in arterial beds of WKY than in SHR, without
      differences in the venous relaxant responses. 6. L-NAME (100 microM) inhibited
      ACh-induced relaxations in arterial and venous beds from both groups of rats.
      Mefenamic acid was without effect on ACh-induced relaxations in either the
      arterial or the venous beds from WKY and SHR. 7. In conclusion, the liberation of
      NO in the perfused mesenteric vasculatures requires an active tone and no
      dysfunction of NO synthase activity is functionally apparent in the mesenteries
      isolated from SHRs. The cyclo-oxygenase pathway is only implicated in the KCl
      induced responses of tissues derived from WKY, but not in the vasodilatations
      induced by ACh in either the arterial or the venous vasculatures from WKY and
      SHR.

PMID- 9179405
TI  - The neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226: equal effects on
      vascular responses to exogenous and endogenous NPY in the pig in vivo.
AB  - 1. The antagonistic effects of the neuropeptide Y (NPY) Y1 receptor antagonist
      BIBP 3226 on equally prominent vascular responses evoked by sympathetic nerve
      stimulation and exogenous NPY were compared during different intravenous (i.v.)
      infusions of the antagonist (0.19-190 nmol kg-1 min-1 for 30 min). 2. High
      frequency sympathetic nerve stimulation in reserpine-treated pigs in vivo evoked
      non-adrenergic vasoconstrictor responses in kidney and hind limb, in the latter
      followed by a long-lasting phase of decreased blood flow. The vascular response
      in the kidney and the long-lasting phase in hind limb resembled the effects of
      exogenous NPY administered i.v. (kidney) and intraarterially (i.a.) (in the hind
      limb, which only responded to higher NPY doses). 3. Plasma levels of BIBP 3226
      reached a plateau within 20 min and the inhibitory effects on vascular responses
      were studied during the last ten minutes of infusion. The elimination of BIBP
      3226 from plasma was found to fit a two-compartment model with an alpha-phase of
      2.0 +/- 0.2 min and a beta-phase of 20.1 +/- 0.9 min. 4. Significant inhibition
      of presumably Y1 receptor-mediated vascular responses evoked by both endogenous
      and exogenous NPY in kidney and hind limb was seen even during low-dose infusion
      of BIBP 3226 (1.9 nmol kg-1 min-1), when plasma levels of the antagonist reached
      59 +/- 8 nM. The maximum inhibitory effects of BIBP 3226 were seen during the
      highest-dose infusion (190 nmol kg-1 min-1), when the long-lasting
      vasoconstrictor responses in hind limb to sympathetic nerve stimulation and
      exogenous NPY administration (i.a.) were abolished. Simultaneously, the vascular
      responses in kidney to exogenous NPY were inhibited by 89% and to sympathetic
      nerve stimulation by 60%. 5. It is concluded that BIBP 3226 has a short half-life
      in plasma and should preferably be given by i.v. infusions to maintain blockade
      and avoid non-specific effects. Furthermore, BIBP 3226 dose-dependently and with
      similar potency antagonizes vascular responses to exogenous and endogenous NPY
      both in the kidney and hind limb of the reserpine-treated pig in vivo. Thus,
      inhibition of vascular responses to exogenous NPY may be a good indicator of the
      dose of this antagonist needed to inhibit sympathetic Y1 receptor-transmission.

PMID- 9179406
TI  - Evidence that NO acts as a redundant NANC inhibitory neurotransmitter in the
      guinea-pig isolated taenia coli.
AB  - 1. The relative contribution of the putative transmitters, nitric oxide (NO) and
      an apamin-sensitive factor, possibly ATP, to inhibitory responses evoked by
      electrical field stimulation (EFS; 0.2-5 Hz, 0.2 ms duration, supra-maximal
      voltage for 10 s) of non-adrenergic, non-cholinergic (NANC) nerves was
      investigated in the guinea-pig isolated taenia coli contracted with histamine (1
      microM). 2. Peak relaxations to EFS (0.2-5 Hz) were tetrodotoxin (1 microM)
      sensitive, maximal at 0.2 Hz and completely resistant to the nitric oxide
      synthase inhibitor, NG-nitro-L-arginine (L-NOARG; 100 microM) in either the
      presence or absence of atropine (1 microM). Furthermore, the specific inhibitor
      of soluble guanylyl cyclase, 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one
      (ODQ; 10 microM), the cytochrome P450 inhibitor and free radical generator, 7
      ethoxyresorufin (7-ER; 10 microM) and the NO scavenger, oxyhaemoglobin (HbO; 30
      microM) had no effect on EFS-induced relaxations alone and in combination with L
      NOARG (100 microM). 3. Maximum relaxation to the NO donor, sodium nitroprusside
      (SNP; 1 microM) was significantly reduced by HbO (30 microM), abolished by 7-ER
      (10 microM) and ODQ (10 microM) but was unaffected by apamin (0.1 microM), an
      inhibitor of small conductance Ca(2+)-activated K+ channels. 4. The relaxation to
      EFS at 0.2 Hz was resistant to apamin but those to 0.5 and 5 Hz were
      significantly reduced. EFS (0.2-5 Hz)-evoked relaxations that persisted in the
      presence of apamin were further significantly inhibited by L-NOARG (100 microM)
      or ODQ (10 microM), but not by HbO (30 microM) or 7-ER (10 microM). 5. ATP (1-30
      microM) produced concentration-dependent relaxations that were abolished by
      apamin (0.1 microM), unaffected by ODQ (10 microM) but only significantly reduced
      by L-NOARG (100 microM) at the lowest concentration of ATP (1 microM) used. 6.
      Nifedipine (0.3 microM), abolished contractions to 67 mM KCl, histamine (10
      microM), endothelin-1 (0.03 microM), 5-hydroxytryptamine (5-HT; 10 microM) and
      the thromboxane-mimetic, 9-11-dideoxy-9 alpha, 11 alpha-methano-epoxy
      prostaglandin F2 alpha (U46619; 0.1 microM). 7. The findings of the present study
      suggest that NO is released during NANC nerve stimulation, but plays no role in
      NANC relaxations in the guinea-pig taenia coli unless the effects of another
      apamin-sensitive, nerve-derived hyperpolarizing factor (NDHF) are blocked. Thus,
      we propose that in this tissue, NO acts as a 'backup' or redundant NANC nerve
      inhibitory transmitter and like NDHF mediates relaxation via hyperpolarization.

PMID- 9179407
TI  - Do physicians' own preferences for life-sustaining treatment influence their
      perceptions of patients' preferences? A second look.

PMID- 9179408
TI  - Prospective autonomy and critical interests: a narrative defense of the moral
      authority of advance directives.

PMID- 9179409
TI  - Approaches responsive to reproductive technologies: a need for critical
      assessment and directions for further study.

PMID- 9179410
TI  - Altering humans--the case for and against human gene therapy.

PMID- 9179411
TI  - Physician-assisted suicide in psychiatry: developments in The Netherlands.

PMID- 9179412
TI  - End-of-life care in The Netherlands and the United States: a comparison of
      values, justifications, and practices.

PMID- 9179414
TI  - CQ sources/bibliography.

PMID- 9179413
TI  - Genetic engineering and environmental ethics.

PMID- 9179415
TI  - Response to "Further exploration of the relationship between medical education
      and moral development" by Donnie J. Self, DeWitt C. Baldwin, Jr., and Frederic D.
      Wolinsky (CQ Vol 5, No 3). Deriving "ought" from "p": methodological and
      theoretical pitfalls in quantitative ethics.

PMID- 9179416
TI  - Response to "Ethical concerns about relapse studies" by Adil E. Shamoo and
      Timothy J. Keay (CQ Vol 5, No 3). Research with vulnerable subjects.

PMID- 9179417
TI  - Response to "Discontinuing life support in an infant of a drug addicted mother:
      whose decision is it?" By Renu Jain and David C. Thomasma (CQ Vol 6, No 1).
      Ethics and drug infants.

PMID- 9179418
TI  - Japanese death factories and the American cover-up.

PMID- 9179419
TI  - Staring at our future.

PMID- 9179420
TI  - Allergy to furred animals.

PMID- 9179421
TI  - Mechanisms of human eosinophil survival and apoptosis.
AB  - Eosinophils, with their potentially harmful armoury of toxic products, have
      available a mechanism by which they can be cleared from the tissues while still
      intact in the absence of an undesirable pro-inflammatory response. However, our
      understanding of the induction and control of apoptosis in eosinophils is still
      incomplete and a great deal of work in this area remains to be done. In other
      cell types, important regulators of apoptosis have been well characterized. These
      include the proto-oncogene bcl-2 and related molecules, the family of proteases
      which share homology with IL-1 beta converting enzyme (ICE) and another protein
      family which interact with products of the proto-oncogene c-myc. These regulators
      act at various points on the apoptosis pathway and it appears their interactions
      are vital in determining whether a cell will survive or die. In particular, the
      ICE-like proteases have been implicated as a universal apoptosis effector which
      is associated with the downstream events of programmed cell death [62]. Whether
      these molecules are involved in the cell death pathway(s) of eosinophils remains
      to be determined. Much of eosinophilic inflammation might be a result of defects
      in pathways controlling eosinophil apoptosis and/or their clearance by phagocytes
      resulting in necrosis and the release of toxic products. A greater understanding
      of the processes involved in the induction and control of eosinophil apoptosis
      might provide novel approaches for therapeutic intervention.

PMID- 9179422
TI  - Source of IL-4 able to induce the development of TH2-like cells.

PMID- 9179423
TI  - IgE response to fur animal allergens and domestic animal allergens in fur farmers
      and fur garment workers.
AB  - OBJECTIVE: The aim of this study was to compare the IgE response to the most
      commonly farmed fur animals with that to domestic animals. METHODS: IgE
      immunoblotting and RAST-inhibition analyses were performed using RAST-positive
      sera from fur workers sensitized to fur allergens and sera from patients
      sensitized to domestic animal allergens. RESULTS: The urine extracts of mink,
      blue fox, silver fox, raccoon dog and fitchew contained more protein bands than
      the fur extracts did. Allergens with the same molecular weight were found in all
      of the fur and urine extracts. The most prominent allergenic bands had molecular
      weights of 62-67 kDa, 23-25 kDa and 18-19 kDa. With crossreacting sera the
      reciprocal RAST inhibition with all five animal extracts indicated common IgE
      binding epitopes, probably common allergens (especially the 62-67 kDa bands).
      Urine and fur contain common allergens, since urine allergens strongly inhibited
      the IgE-binding to fur allergens. The IgE binding to allergenic bands of fur
      animal extracts was also observed in immunoblotting when dog and cat RAST
      positive sera were used, but not for cow RAST-positive sera. RAST inhibition of
      dog-positive sera with fur animal extracts and fur-positive sera with dog extract
      confirmed the crossreactivity of these IgE antibodies. No such inhibition was
      seen with cow extract. CONCLUSION: The results of the RAST inhibition and
      immunoblotting suggest that fur animals have IgE binding epitopes or allergens in
      common with cat and dog--possibly albumin--but not with cow.

PMID- 9179425
TI  - Hay fever, asthma and number of older siblings--a twin study.
AB  - BACKGROUND: It has been suggested that allergic sensitization is inversely
      related to the number of siblings in the family. OBJECTIVES: To study whether a
      similar relation can be observed for hay fever and asthma among Finnish
      adolescents in a population with relatively low prevalence of atopic diseases.
      METHODS: A questionnaire mailed to a nationwide sample of 1849 families with 16
      year-old twins assessing the cumulative incidence of doctor-diagnosed hay fever
      and asthma among the adolescents and the number of older siblings in the family
      by parental report. RESULTS: The cumulative incidence of hay fever was
      significantly lower among the adolescents with three or more older siblings
      (3.9%, 95% CI = 1.2-6.5%) compared with adolescents with fewer older siblings
      (12.7%, 95% CI = 11.4-14.0%). There was no difference in the cumulative incidence
      of asthma among the adolescents according to the number of older siblings in the
      family. CONCLUSIONS: Large number of older siblings appears to be protective
      against the development of hay fever.

PMID- 9179424
TI  - Occupational asthma caused by triglycidyl isocyanurate (TGIC).
AB  - BACKGROUND: Polyester powder paints are extensively used in metal painting.
      Triglycidyl isocyanurate (TGIC), an epoxy compound, is often used as a hardener.
      Several cases of allergic eczema from occupational exposure to TGIC have been
      reported in the literature. OBJECTIVE: We examined a 36-year-old non-smoking man
      who worked mainly as a spray painter, using a polyester powder paint containing
      4% TGIC. During painting he used protective clothing and a motorized breathing
      protector. After 4 years he developed eczema on his hands, face and body, and an
      occupational allergic eczema caused by TGIC was diagnosed. He also suffered from
      powder-paint-related asthmatic symptoms. METHODS: Occupational asthma was
      diagnosed in accordance with the accepted guidelines. Inhalation challenge tests
      were performed with the paint and TGIC. RESULTS: Spirometry showed slight
      obstruction; the blood eosinophils and serum IgE value were elevated. Skin-prick
      tests with common environmental allergens were negative. The challenge test with
      lactose powder was also negative. A challenge test with a paint containing TGIC
      (4%) induced a dual reaction in PEF and a late 23% fall in FEV1. A test with TGIC
      (4%) mixed with lactose induced a dual PEF reaction, and also dual changes in
      spirometry. The PD15 in the histamine challenge test decreased significantly
      after the challenge tests. CONCLUSIONS: To our knowledge this is the first
      diagnosed case of occupational asthma caused by TGIC. This case report emphasizes
      the importance of protecting both the skin and respiratory tract of workers
      against chemicals such as TGIC, capable of causing skin and respiratory allergy.

PMID- 9179426
TI  - The use of serum eosinophil cationic protein (ECP) in the management of steroid
      therapy in chronic asthma.
AB  - BACKGROUND: Corticosteroid therapy has become the mainstay in the treatment of
      asthma. However, the risk-benefit balance in the patient calls for assessment of
      the state of inflammation in the airways. In this respect serum eosinophil
      cationic protein (ECP) might be a marker, which can easily be measured in a
      clinical setting. Studies have indicated a relation between level of serum ECP
      and activity and severity in asthma. OBJECTIVE: To investigate the feasibility to
      guide steroid therapy on the basis of the level of serum ECP in patients with
      chronic asthma. METHODS: Twenty adult patients on maintenance inhaled steroid
      therapy visited the chest clinic once every 2 months over a 12-month period. At
      each visit a short history, blood sample for ECP and number of eosinophils,
      baseline spirometry, and histamine inhalation provocation test (PC20) were
      obtained. On the basis of level of ECP, adjustments in daily dose of steroids
      were considered. Data were compared with those of a previous 6-month ECP
      evaluation study in these same patients. RESULTS: In 10 patients mean dose of
      inhaled steroids was decreased > or = 25%. ECP rose slightly (antilogged mean
      from 9.06 to 11.8 micrograms/L) and lung function decreased slightly (mean FEV1
      %predicted from 85.5 to 81.6). In seven patients mean dose of inhaled or oral (n
      = 2) steroids was increased > or = 25%. In this group ECP decreased but remained
      elevated at > or = 20 micrograms/L (antilogged mean from 30.5 to 25.6
      micrograms/L) and lung function improved (mean FEV1 %predicted from 67.2 to
      74.5). In both groups patients' scores of asthmatic well-being increased
      significantly, and PC20 did not show a trend. Exacerbation rate remained the same
      in the decreased and the no change group (n = 3, in which no substantial change
      in steroid dose occurred), but was reduced by about 50% in the increased group.
      CONCLUSION: From this observational study it is concluded that adjusting steroid
      therapy guided by serum ECP-level may be helpful in tailoring asthma treatment.

PMID- 9179427
TI  - Asthma, bronchial hyperreactivity and mediator release in children with birch
      pollinosis. ECP and EPX levels are not related to bronchial hyperreactivity.
AB  - BACKGROUND: Symptoms of allergic asthma are triggered by allergen exposure
      inducing allergic inflammation and hyperreactivity of the bronchi. OBJECTIVES: To
      investigate the possible relationship between clinical symptoms and signs of
      asthma, i.e. bronchial variability as measured by peak expiatory flow rate
      (PEFR), bronchial hyperreactivity (BHR) and mediators of allergic inflammation.
      METHODS: Twenty-eight children with pollinosis, but no obvious history of asthma,
      were studied at three occasions, i.e. before, during and after (autumn) the birch
      pollen season. Twelve children sensitive to birch pollen were considered as the
      case group. Sixteen children, who were only clinically sensitive to grass pollen,
      served as controls. Subjective symptoms of asthma were recorded by visual
      analogue scale, BHR was estimated by methacholine bronchial provocation tests,
      bronchial variability PEFR and circulating mediators of inflammation, i.e.
      eosinophil cationic protein, eosinophil protein X, myeloperoxidase and tryptase
      in serum. RESULTS: Bronchial hyperreactivity and by PEFR was more pronounced
      after than during the season (P < 0.01), whereas eosinophil mediators and the
      peak expiratory flow rate increased during the season (P < 0.05). Except for
      between PEFR variability and BHR in the autumn (r = 0.45; P = 0.014), no
      correlations were found. However, in the autumn, the majority of children were
      still hyperreactive in the bronchi and showed PEFR variability but the levels of
      eosinophil mediators in serum had returned to normal levels. CONCLUSION: Signs
      and symptoms of asthma did not correlate with serum levels of mediators of
      allergic inflammation. Bronchial hyperreactivity and PEFR variability persisted
      after the pollen season when signs of bronchial inflammation had disappeared. We
      hypothesize that eosinophil mediators and other markers of allergic inflammation
      disappear after the late-phase reaction, whereas BHR persists. This would explain
      the lack of correlation between the levels of eosinophil mediators in serum and
      symptoms of asthma and BHR.

PMID- 9179428
TI  - Comparison of the ISAAC video questionnaire (AVQ3.0) with the ISAAC written
      questionnaire for estimating asthma associated with bronchial hyperreactivity.
AB  - BACKGROUND: A standardized protocol is essential for international comparisons of
      asthma prevalence and severity. The International Study of Asthma and Allergies
      in Childhood (ISAAC) used a standardized written questionnaire (WQ) and a video
      questionnaire (AVQ3.0) to survey the prevalence and severity of asthma in 13-14
      year-old schoolchildren in different countries. OBJECTIVE: To compare the
      effectiveness of WQ and AVQ3.0 in predicting bronchial hyperresponsiveness (BHR),
      defined as having a provocation dose of inhaled methacholine causing a 20% fall
      in baseline FEV1 of 7.8 mumol. METHODS: One hundred and eighty-nine Chinese
      schoolchildren completed a written questionnaire followed by a video
      questionnaire on asthma symptoms. They then underwent bronchial challenge to
      methacholine. RESULTS: Fair correlations were seen between the first two
      corresponding questions (moderate wheezing at rest and exercise wheeze) in the
      two questionnaires with Kapper indices of 0.44 and 0.43, respectively. The
      ability to predict BHR, as indicated by the Youden's index, was similar between
      the corresponding questions of the two questionnaires, except for 'severe wheeze'
      which had a significantly higher Youden's index in AVQ3.0 (0.44) than the
      corresponding question in WQ (0.11, P < 0.05). CONCLUSION: The ISAAC
      International video questionnaire is at least as effective as the ISAAC written
      questionnaire in predicting BHR. It therefore provides a simple and valid tool
      for international comparisons of asthma prevalence and severity.

PMID- 9179429
TI  - Studies of the effects of inhaled magnesium on airway reactivity to histamine and
      adenosine monophosphate in asthmatic subjects.
AB  - BACKGROUND: Magnesium is a cation with smooth muscle relaxant and anti
      inflammatory effects and may therefore have a role in the therapy of asthma.
      Several studies have investigated the effects of intravenous magnesium in acute
      or stable asthma, but little is known about the effects of inhaled magnesium.
      OBJECTIVE: To measure the effects of a single inhaled nebulized dose of 180 mg
      magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor
      (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate
      [AMP]) in asthmatic subjects. METHODS: Two separate randomized, double-blind,
      placebo-controlled crossover studies, each involving 10 asthmatic subjects. In
      the histamine study, airway reactivity to histamine was measured and lung
      function allowed to recover spontaneously over 50 min before administering
      nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine
      was then measured at 5 and 50 min. In the AMP study, a single measurement of
      airway reactivity was made 5 min after magnesium or placebo. RESULTS: In the
      histamine study, the provocative dose required to reduce FEV1 by 20% (PD20FEV1)
      was significantly lower after magnesium than after placebo, by a mean (95% CI) of
      1.02 (0.22-1.82) doubling doses at 5 min (P = 0.018), and 1.0 (0.3-1.7) doubling
      doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also significantly
      lower at 5 min after magnesium than after saline, by 0.64 (0.12-1.16) doubling
      doses (P = 0.023), though this difference was not statistically significant after
      adjustment for differences in baseline FEV1 on the two study days. CONCLUSIONS:
      Inhaled magnesium did not protect against the effects of these direct and
      indirect bronchoconstrictor stimuli in subjects with asthma, and may have
      increased airway reactivity to histamine.

PMID- 9179430
TI  - Fluticasone propionate nasal spray is more effective and has a faster onset of
      action than placebo in treatment of rhinitis medicamentosa.
AB  - BACKGROUND: Controversy still exists about the treatment of rhinitis
      medicamentosa and treatment has never been objectively evaluated. OBJECTIVE: To
      study the effect of fluticasone propionate aqueous nasal spray compared to
      placebo nasal spray in the treatment of rhinitis medicamentosa. METHODS: A
      parallel randomized, double-blind study was conducted to evaluate the treatment
      of rhinitis medicamentosa. Two groups containing 10 patients with rhinitis
      medicamentosa in each group stopped their overuse of nasal vasoconstrictor spray
      immediately and were treated with either fluticasone propionate nasal spray once
      daily 200 micrograms, or placebo nasal spray for 14 days. The nasal mucosal
      swelling was recorded with rhinostereometry, acoustic rhinometry and a peak
      inspiratory flow meter. Nasal stuffiness was estimated on a visual analogue scale
      in the morning and in the evening of each day. RESULTS: The mucosal swelling
      decreased after 7 and 14 days of treatment with fluticasone propionate as well as
      placebo, but the reduction was significantly greater after treatment with
      fluticasone propionate. The symptom scores for nasal stuffiness showed a marked
      reduction during the treatment period in both groups, but there was a faster
      onset of symptom reduction after treatment with fluticasone propionate.
      CONCLUSION: Fluticasone propionate is more effective and has a faster onset of
      action than placebo in the treatment of rhinitis medicamentosa. An adequate
      treatment of these patients consists of a combination of vasoconstrictor
      withdrawal and a topical corticosteroid to alleviate the withdrawal process.

PMID- 9179431
TI  - Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of
      mediators from human Fc epsilon RI+ cells.
AB  - BACKGROUND: Loratadine, a novel histamine H1-receptor antagonist, is effective in
      the treatment of patients with seasonal and perennial rhinitis and some allergic
      skin disorders. Histamine and other chemical mediators are synthesized and
      immunologically released by human peripheral blood basophils and tissue mast
      cells (Fc epsilon RI+ cells). OBJECTIVE: To evaluate the effects of loratadine
      and its main metabolite, desethoxylcarbonyl-loratadine (des-loratadine), on the
      immunological release of preformed (histamine and tryptase) and de novo
      synthesized mediators (leukotriene C4: LTC4 and prostaglandin D2:PGD2) from human
      Fc epsilon RI+ cells. METHODS: Human Fc epsilon RI+ cells purified from
      peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated
      with loratadine and des-loratadine before immunological challenge with Der p 1
      antigen or anti-Fc epsilon RI. The release of preformed mediators (histamine and
      tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants
      of human Fc epsilon RI+ cells. RESULTS: Preincubation (15 min, 37 degrees C) of
      purified (36-74%) basophils with loratadine (3 x 10(-6)-10(-4)M) and des
      loratadine before Der p 1 antigen or anti-Fc epsilon RI challenge concentration
      dependently (5-40%) inhibited the release of histamine and LTC4. Loratadine (3 x
      10(-6)-10(-4)M) and des-loratadine also inhibited (10-40%) histamine, LTC4, and
      PGD2 release from purified HLMC (16-68%) activated by anti-Fc epsilon RI.
      Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine caused concentration-dependent
      inhibition (10-40%) of histamine, tryptase, LTC4, and PGD2 release from purified
      HSMC (24-72%) immunologically challenged with anti-Fc epsilon RI. CONCLUSION:
      These results indicate that loratadine and its main metabolite have anti
      inflammatory activity by inhibiting the release of preformed and de novo
      synthesized mediators from human Fc epsilon RI+ cells.

PMID- 9179432
TI  - The interaction of tumour necrosis factor alpha and endothelin-1 in pathogenetic
      models of asthma.
AB  - BACKGROUND: There is evidence that tumour necrosis factor alpha (TNF alpha) may
      be an important mediator in initiating asthmatic airway inflammation. It has been
      proposed that endothelin-1 (ET-1) is involved in bronchoconstriction and airway
      remodelling in asthma. It is not known, however, if there is any interaction
      between TNF alpha and ET in perpetuating airway inflammation in asthma.
      OBJECTIVE: The present study aimed to determine the activities of ET-1 and TNF
      alpha in ovalbumin-sensitized guinea pigs and their roles in the development of
      airway inflammation. METHOD: Twelve guinea pigs were sensitized by ovalbumin
      injection and aerosol inhalation. ET-1 levels were measured in both
      bronchoalveolar lavage fluid (BALF) and plasma by 125-labelled endothelin-1 (ET
      1) radioimmunoassay. The TNF alpha activity released from alveolar macrophage
      (AM) in BALF was estimated by ELISA. Cultured bovine airway smooth muscle cells
      (BASMCs) were treated with TNF alpha (1000 units/5 x 10(4) cells) for different
      times. ET-1 levels in harvested medium from these cells were measured by
      radioimmunoassay. Cultured human fetal lung fibroblasts (HFLFs) were incubated
      with ET-1 (10(-8) approximately 10(-6)M), then 3HTdR incorporation to these cells
      and cell counting were performed. The effects of ET-1 stimulation on the
      granulocyte macrophage colony stimulating factor (GM-CSF) gene expression in
      HFLFs were estimated by using RT-PCR method. RESULTS: ET-1 levels in both plasma
      and BALF were significantly higher in ovalbumin-sensitized guinea-pigs compared
      with those in controls (422.27 +/- 175.0 pg/mL vs 277.311 +/- 88.0 pg/mL, P <
      0.05, 81.22 +/- 16.15 vs 49.81 +/- 12.64 pg/mL, P < 0.05) while TNF alpha
      activity was also significantly increased in the OVA-sensitized group compared
      with that in the control group (6010 +/- 1900 pg/mL vs 2810 +/- 450 pg/mL, P <
      0.05). The ET-1 level in harvested medium of BASMCs rose significantly in 12 h in
      the TNF-alpha treated group (from < 5 pg/mL to 53.72 +/- 14.3 pg/mL, P < 0.001),
      and remained at a similar level for 24 h in the TNF alpha treated group. It was
      shown that ET-1 not only stimulated cell proliferation but also induced GM-CSF
      mRNA expression in HFLFs. CONCLUSION: ET-1 levels in both plasma and BALF and TNF
      alpha release from macrophage are increased significantly in ovalbumin-sensitized
      guinea-pigs. TNF alpha stimulates ET-1 secretion from cultured BASMCsw; ET-1
      accelerates cell proliferation and induces GM-CSF mRNA expression in the human
      fetal lung fibroblast.

PMID- 9179433
TI  - Aspirin-induced asthma and HLA-DRB1 and HLA-DPB1 genotypes.
AB  - BACKGROUND: Aspirin-induced asthma (AIA) affects one in 10 individuals with adult
      onset asthma. It is not known if aspirin sensitivity is due to immune mechanisms
      or to interference with biochemical pathways. OBJECTIVE: The study aimed to test
      for possible involvement of the genes of the Major Histocompatibility Complex
      (MHC) in AIA. METHODS: HLA-DPB1 and HLA-DRB1 genotyping was carried out by DNA
      methods in 59 patients with positive challenge tests for AIA and in 48 normal and
      57 asthmatic controls. RESULTS: The DPB1*0301 frequency was increased in AIA
      patients when compared with normal controls (19.5% vs 5.2%, Odds Ratio = 4.4, 95%
      Confidence Interval (CI) 1.6-12.1, P = 0.002), and compared with asthmatic
      controls (4.4%, OR = 5.3, 95% CI = 1.9-14.4, P = 0.0001). The frequency of
      DPB1*0401 in AIA subjects was decreased when compared with normal controls (28.8%
      vs 49.0%, OR = 0.42, 95% CI = 0.24-0.74, P = 0.003) and asthmatic controls
      (45.6%, OR = 0.48, 95% CI = 0.28-0.83, P = 0.008). The results remained
      significant when corrected for multiple comparisons. There were no significant
      HLA-DRB1 associations with AIA. CONCLUSION: The presence of an HLA association
      suggests that immune recognition of an unknown antigen may be part of the
      aetiology of AIA.

PMID- 9179434
TI  - Sensitivity to bee and wasp venoms: association with specific IgE responses to
      the bee and wasp venom and HLA DRB1 and DPB1.
AB  - BACKGROUND: Stings from bees and wasps can cause systemic reactions which can be
      fatal in some individuals. In these venom-sensitive patients, specific IgE to the
      venom is produced and is considered to participate in the adverse reactions. This
      immune response requires antigen presentation by human leucocyte antigens (HLA)
      class II molecules, which includes DR and DP, which are present on antigen
      presenting cells. OBJECTIVE: To test for associations between HLA class II DRB1
      and DPB1 alleles and life-threatening sensitivity to both bee and wasp venoms. To
      establish further whether any associations are independent of the atopy
      phenotype. METHODS: A total of 33 bee- and 44 wasp-venom-sensitive patients was
      studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO)
      probing of PCR products, and DPB1 genotypes by amplified fragment length
      polymorphism (AFLP) analysis. Total and specific IgE were measured using the
      Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only
      were termed monosensitive and those with additional specific IgE to HDM and/or GP
      were termed polysensitive. RESULTS: Allele frequencies were compared to an
      unrelated control population. The 33 bee-sensitive patients had a greater
      prevalence of DRB1*07 alleles than the control subjects, 26% vs 14%, with an odds
      ratio (OR) of 2.1 (95% CI, 1.2-3.7, P = 0.015, corrected for multiple
      comparisons, Pc = ns). This association was confined to the 15 monosensitive bee
      patients, who had a 43% DRB1*07 allele frequency when compared with 11% in the 18
      polysensitive bee patients, OR 6.1 (95% CI, 1.73-22, P = 0.004, Pc = 0.05), and
      when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95%
      CI, 1.72-9.0, P = 0.002, Pc = 0.02). The 44 wasp-sensitive patients had an
      increase in the DRB1*11 allele when compared with the control subjects, 13% vs
      6%, with an OR 2.2 (95% CI, 1.0-4.6, P = 0.04, Pc = NS), and a decreased
      prevalence of DRB1*04 alleles, 10% vs 19%, with an OR 0.33 (95% CI, 0.24-0.99, P
      = 0.04, Pc = NS), but these were not significant when multiple comparisons were
      taken into account. The DPB1 alleles were not significantly different between the
      venom sensitive patients and the controls. CONCLUSION: Patients monosensitive to
      bee venom had a significantly greater prevalence of DRB1*07 alleles than the non
      venom, control population suggesting that IgE responses in these patients may, in
      part be controlled by immune response HLA class II genes. These results are also
      suggestive of wasp-sensitive patients having a higher prevalence of DRB1*11 and a
      lower prevalence of DRB1*04 than the control population.

PMID- 9179435
TI  - Cell surface expression of two major yeast allergens in the Pityrosporum genus.
AB  - BACKGROUND: We have previously identified two major allergens of Pityrosporum
      orbiculare and characterized these as 37 kDa and 67 kDa proteins. OBJECTIVE: In
      the present study we have investigated the presence and subcellular location of
      the 37 kDa and 67 kDa allergen components in various members of the genus
      Pityrosporum as well as in Candida albicans, Candida parapsilosis and
      Saccharomyces cerevisiae. METHODS: To detect both cell surface and intracellular
      expression of the allergens, flow cytometry and confocal laser scanning
      microscopy (CLSM) were used. The cells were stained with indirect
      immunofluorescent (IIF) or alkaline phosphatase anti-alkaline phosphatase (APAAP)
      methods using mouse monoclonal antibodies (MoAbs). RESULTS: Ninety-five per cent
      of the P. orbiculare (P. ovale) cells cultured for 4 days showed cell surface
      binding of the anti-37 kDa MoAb and 88% of the cells bound the anti-67 kDa MoAb
      when analysed with IIF and flow cytometry. It was found that the members of the
      genus Pityrosporum (Malassezia), P. pachydermatis and M. sympodialis, expressed
      the 37 kDa and 67 kDa allergens to a similar extent as did P. orbiculare. Less
      than 5% of the cells of the genus Candida and S. cerevisiae showed positive
      staining with the MoAbs. The CLSM revealed that the 37 kDa and the 67 kDa
      components were located to the cell wall and could not be detected inside the
      acetone fixed and APAAP stained yeast cells of the genus Pityrosporum. When the
      yeast cells were cultured for more than 4 days the expression of both allergens
      decreased significantly. CONCLUSION: All three members of the genus Pityrosporum
      express the 37 kDa and 67 kDa major allergens on the cell surface, whereas these
      proteins could virtually not be detected in the Candida genus and S. cerevisiae.

PMID- 9179436
TI  - Localization of antigenic sites on Der p 2 using oligonucleotide-directed
      mutagenesis targeted to predicted surface residues.
AB  - BACKGROUND: Understanding the molecular nature of allergen-antibody interactions
      is important to understanding the mechanism of conventional immunotherapy as well
      as to designing alternative immunotherapeutic strategies. Many important
      allergens have been cloned and expressed, making it possible to apply recombinant
      DNA techniques to dissect antigenic determinants. OBJECTIVE: The aim of this
      study was to use predictive algorithms and site-directed mutagenesis to
      investigate monoclonal antibody and IgE antibody epitopes of the major house dust
      mite allergen Der p 2. METHODS: Computer algorithms were used to assess the
      primary amino acid sequence of Der p 2 and to identify regions of hydrophilic and
      flexible sequence. Subsequently, site-directed mutagenesis was used to generate
      amino acid substitutions at hydrophilic residues at positions 44-46 and at
      position 100. The variants were tested in a competitive inhibition ELISA with
      four group 2-specific murine monoclonal antibodies and with human IgE antibody
      from mite allergic patients. RESULTS: Conservative amino acid substitutions at
      position 44-46 did not distinguish IgE antibody epitopes, but did suggest that
      these residues are involved in the epitope defined by one monoclonal antibody,
      15E11. Non-conservative substitution of proline at this position reduced binding
      to all four monoclonal antibodies, as well as IgE antibody, by 50-80%. Point
      mutants at position 100 mapped the epitopes of two monoclonal antibodies, 7A1 and
      13A4, previously shown to bind the same region of Der p 2. In addition, the two
      variants tested at this position showed distinct inhibition curves with these two
      monoclonal antibodies indicating differences in fine specificity. CONCLUSIONS:
      Using predictive algorithms, in the absence of tertiary structural information,
      we have been able to localize important B cell determinants on Der p 2. The
      results suggest that it is possible to modulate antibody recognition of allergens
      using site-directed mutagenesis and that this approach may provide a new strategy
      for allergen specific immunotherapy.

PMID- 9179437
TI  - The life and work of Jack Pepys.

PMID- 9179439
TI  - Aspergillus fumigatus antigens: the Pepys' years.

PMID- 9179440
TI  - Curriculum vitae. Jack (Jacob) Pepys. Born: 15 May, 1914, died: 9 September,
      1996, London, UK.

PMID- 9179441
TI  - Extrinsic allergic alveolitis (hypersensitivity pneumonitis): past, present and
      future.

PMID- 9179442
TI  - Impact of the environment on allergic lung diseases.

PMID- 9179444
TI  - Aetiology of occupational asthma.

PMID- 9179443
TI  - The investigation of airway inflammation in asthma: sputum examination.

PMID- 9179445
TI  - Mechanisms of occupational asthma.

PMID- 9179446
TI  - Allergic bronchopulmonary aspergillosis.

PMID- 9179447
TI  - Discovery and development of IgE assays.

PMID- 9179448
TI  - Mast cells, eosinophils and fibrosis.
AB  - We have presented results that increase our understanding of the roles MC and EOS
      play in modulating fibrotic processes. In vitro studies have provided clear-cut
      evidence for the direct involvement of these two inflammatory cells in enhancing
      proliferation, and either enhancing or decreasing collagen synthesis in human
      fibroblasts isolated from different anatomical locations. In addition, we have
      shown that MC and EOS interactions can also take part in modulating fibrosis. In
      vivo studies in murine and human cGVHD showed that MC activation is detrimental,
      and that MC stabilization therapy may be helpful in treating the fibrotic outcome
      of this disease. Much is still obscure. It is, for example, important to define
      the MC and EOS mediators involved in the modulation of fibroblast properties, and
      their pattern of influence, keeping in mind the ultimate goal of defining new
      therapeutic targets for the treatment of fibrotic diseases.

PMID- 9179449
TI  - Human late asthmatic reactions.

PMID- 9179450
TI  - Modification of oral contraceptive relationships on breast cancer risk by
      selected factors among younger women.
AB  - In a case-control study of 1647 breast cancer cases and 1501 population controls
      under 45 years of age, potential modifying effects of other risk factors on the
      relationship of oral contraceptives to breast cancer were examined. Among the
      total series of study subjects, the relationship of extended pill usage was
      greater in non-white than white women. Oral contraceptive associations, however,
      did not appear to be substantially modified by other risk factors, including
      parity, body size, or family history of breast cancer (apart from a somewhat
      enhanced relationship among subjects who reported a sister with breast cancer.
      Further, oral contraceptive relationships did not vary by a history of benign
      breast disease, although the majority of subjects began pill usage prior to the
      development of benign breast disease. Among the women under the age of 35, in
      whom oral contraceptive relationships were heightened (over a twofold excess risk
      for use of 5 years or longer), pill relationships were less modified by race than
      in the total series. Although among these younger subjects there was no effect of
      pill usage in heavy women, and an enhanced relationship among heavier consumers
      of alcoholic beverages, these interactive effects were not statistically
      significant. The findings of this study generally support no substantial
      variation in oral contraceptive relationships by other breast cancer risk
      factors, although some further attention might be warranted regarding possible
      modifying effects of race, body size, type of relative with breast cancer, and
      alcohol consumption.

PMID- 9179451
TI  - Use of Norplant implants in asymptomatic HIV-1 infected women.
AB  - The study of Norplant implants use in HIV-1 infected women was conducted at the
      Family Planning Clinic, Department of Obstetrics and Gynaecology. Faculty of
      Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, from
      January 1993 to June 1996. The purpose of the study was to evaluate efficacy,
      clinical effects, side effects, and menstrual patterns of the Norplant system in
      HIV-1 infected acceptors. Forty one cases of asymptomatic HIV-1 positive women
      voluntarily participated in using Norplant implants after delivery or abortion.
      The mean age was 25.4 years. The most common menstrual pattern was irregular
      bleeding (63.4%). Mean blood pressure, body weight, and hemoglobin level were not
      different at insertion and at 12 months (p > 0.05). No pregnancy occurred during
      a 12-month period. It was concluded that the Norplant system was safe,
      efficacious, and well tolerated in HIV-1 positive women and is an appropriate
      contraception in these women.

PMID- 9179452
TI  - Alteration of human sperm kinematics in cervical mucus due to nonoxynol-9.
AB  - Traditional endpoints of the double-ended test (DET), a contraceptive screening
      assay used to evaluate the ability of a compound to permeate cervical mucus and
      inhibit sperm progression, ignore important information about sublethal effects
      upon sperm cells. Improved contraceptive agents may capitalize on such sublethal
      aspects. This study utilized a DET testing protocol that included measurement of
      human sperm motion characteristics as an indicator of cell function within
      spermicide-exposed human mucus. The currently available spermicide nonoxynol-9
      (N9) was used as the test compound and was dissolved in two different delivery
      solutions, deionized (DI) water and saline, to evaluate the effects of the
      osmolarity and pH of the delivery vehicle on test results. The N9-water treatment
      demonstrated significantly greater activity than the N9-saline treatment in terms
      of all measured variables, exhibiting an apparent "biopermeation" distance
      approximately 3 mm further into the mucus. The DI water control treatment
      displayed less activity than N9-saline in terms of the vanguard penetration
      distance, but comparable or greater activity in terms of inhibiting kinematic
      variables. The saline control treatment had no effect in terms of any measured
      variable. Dose responses to N9 of sperm in mucus were inferred from DET results
      combined with direct measures of N9 diffusion. These were compared to dose
      responses to N9 of seminal sperm, indicating that N9 inhibits sperm motion at
      lower concentrations in mucus than in semen.

PMID- 9179453
TI  - Multicenter study of endocrine function and plasma lipids and lipoproteins in
      women using oral contraceptives containing desogestrel progestin. UK Desogen
      Study Group.
AB  - We assessed endocrine function and plasma lipid and lipoprotein concentrations in
      112 women given a monophasic oral contraceptive containing 30 micrograms ethinyl
      estradiol and 150 micrograms desogestrel. These women were participating in a
      larger trial of cycle control and safety. Plasma concentrations of
      gonadotrophins, estradiol, and progesterone fell over the 18 months of this
      study, consistent with suppression of the hypothalamic-pituitary-ovarian (HPO)
      axis. There was no consistent effect on plasma prolactin concentrations.
      Concentrations of total triiodothyronine, thyroxine, and cortisol increased,
      tracking increases in their binding proteins. Within 6 months, plasma total
      cholesterol concentrations had increased by 12% (p < 0.001) with no effect on
      those of low density lipoproteins. Concentrations of triglycerides and high
      density lipoprotein cholesterol increased by 79% and 14%, respectively (both p <
      0.001). Monophasic ethinyl estradiol/desogestrel effectively suppressed the HPO
      axis. Other endocrine changes were typical of oral contraceptives containing
      ethinyl estradiol. The increase in triglyceride concentrations is not considered
      to increase cardiovascular risk, whereas the increase in high-density
      lipoproteins may be protective.

PMID- 9179454
TI  - Contraceptives for lactating women: a comparative trial of a progesterone
      releasing vaginal ring and the copper T 380A IUD.
AB  - From approximately one week before normal ovulation resumes, lactating women
      require protection against pregnancy by a contraceptive that is safe for both
      infant and mother in a multicenter one-year study, the natural hormone,
      progesterone, delivered vaginally by a sequence of four contraceptive rings
      designed for continuous use, was evaluated as a contraceptive for nursing mothers
      in comparison with the Copper T 380A IUD. Individual rings release in effective
      average dose of 10 mg day for a 3 month period. Evaluation included measures of
      lactational performance as well as of contraceptive efficacy and safety to mother
      and child. Nine participating clinics enrolled 802 ring users and 734 IUD
      acceptors between postpartum days 29 and 63. Life table analyses were performed
      with parallel decrements for ring and IUD subjects. Continuation in the study and
      analysis required that subjects not stop breastfeeding. The ring, with a one-year
      pregnancy rate of 1.5 per 100, did not differ significantly from the IUD with
      respect to contraceptive effectiveness (p > 0.05). More than half of the ring
      subjects were continuing at 6 months post admission and a quarter (23.5 per
      hundred) were still using the ring and breastfeeding one year after admission.
      Women with the IUD, however, had higher continuation rates (p < 0.001) at both
      time points. The largest single decrement for each method was that for weaning.
      Ring users had more complaints of vaginal problems but had fewer vaginal
      disorders on examination. At 12 months postpartum, 46 per 100 continuing ring
      users remained in amenorrhea. Lactation performance and the health and weight
      gain of the infants were similar among users of either regimen.

PMID- 9179455
TI  - Natural family planning: suitability of the CUE method for defining the time of
      ovulation.
AB  - The purpose of this study was to compare the CUE method for family planning with
      the Ovulation Detection Method for defining the fertile phase of the menstrual
      cycle. We evaluated 42 cycles from 10 women in Monterrey, Mexico, who were
      monitored by basal body temperatures, urinary LH, pelvic ultrasound, and the CUE
      monitor. The fertile phase of the cycle was adequately defined in all cycles
      using the CUE method, and in 35 cycles (83.3%) by the Ovulation Method. Using our
      protocol, the period of recommended abstinence with the CUE method is 9 days and
      with the Ovulation Method 11 days. The CUE method accurately defines the fertile
      phase of the menstrual cycle, thus improving the predictability of ovulation for
      women who use natural methods of birth control.

PMID- 9179456
TI  - Inhibition of ovulation with transdermal estradiol and oral progestogens in
      perimenopausal women.
AB  - The effects of 6 months of combined hormone therapy with transdermal estradiol
      (0.05 mg/day x 21 days) and different oral progestogens (10 mg/day
      medroxyprogesterone acetate [MPA] in the last 12 days, 10 mg/day dihydrogesterone
      in the last 12 days, and 50 mg/day cyproterone in the first 10 days), on
      menopausal symptoms and hypothalamo pituitary-ovarian function were studied in
      normal perimenopausal women. The study included 38 perimenopausal women, aged 43
      49 years, with regular cycles of 26-32 days in length and menopausal symptoms.
      Endocrine status was determined by assay of basal levels of gonadotropins (LH,
      FSH), E2, and P every week until menstrual bleeding, before and during the first
      month of therapy. Plasma levels of LH and FSH were suppressed in the first month
      of therapy while E2 had a mean value of 45 +/- 12 pg/ml. Ultrasound examination
      and low levels of P indicated a complete block of ovulation and hypothalamo
      pituitary-ovarian activity. All women reported the disappearance of vasomotor
      symptoms and nocturnal sweating. Transdermal estradiol and oral progestogens were
      well tolerated. This study shows that combined hormone therapy with low doses of
      transdermal estrogen patches and different oral progestogens reduces menopausal
      symptoms and also safeguards against unwanted pregnancies in the perimenopausal
      period.

PMID- 9179458
TI  - A fifteen-year review of female sterilization by minilaparotomy under local
      anesthesia in Kenya.
AB  - This paper is a comprehensive review of literature concerning the Kenyan
      experience with female sterilization through minilaparotomy under local
      anesthesia (ML/LA). A composite picture from analysis of several studies that
      include some 12,000 clients since 1979 reveals an average Kenyan user to be 31-34
      years old (SD 4.9) with 5.9-6.8 children (SD 1.7-1.8). In up to 96% of cases, the
      indication for choosing sterilization is personal socio-economic considerations.
      The majority of clients (97%-99%) report satisfaction with their choice of
      sterilization at the first follow-up visit, and 96-99% state that they would
      recommend the method to others. The operation takes an average of 14 min (SD 4.5
      5.3) "skin-to-skin" through a 2.5.2.8 cm incision (SD 0.5). A mean of 18 cm3 of
      1% lignocaine is used (SD 2.7). Most clients (76.4%) have no post-operative
      complaints; those who do have any complaints report minor transitory problems.
      Similarly, most clients (96%) have moderate, little, or no peri-operative pain,
      but 1.9%-5% report much pain. The intra-operative and early complication rate is
      0.9%. Some 3.3% of clients suffer at least one complication, some multiple, and
      the complication rate at 6 weeks is 4.1%, with major complications occurring in
      0.7% of cases, and minor complications in 3.4%. The crude failure rate is 0.4% in
      the first year and 0.1% in the second year, when corrected for luteal phase
      pregnancies, which account for 50% of all "failures," the actual failure rate is
      0.2% in the first year and 0.1% in the second year both for interval and
      postpartum procedures. This literature review finds outpatient ML/LA to be a
      relatively safe, simple, effective, and well-accepted option for most Kenyan
      couples seeking contraception that is intended to be permanent. Counseling,
      adequate client assessment, and voluntarism have been shown to be essential
      elements, not only for client satisfaction and avoidance of possible future
      regret, but also for technical ease of the operative procedure. Recommendations
      that derive from the Kenya experience are made.

PMID- 9179457
TI  - Effect of vitamin B6 on the side effects of a low-dose combined oral
      contraceptive.
AB  - Analogous to recommendations for treatment of side effects of early pregnancy and
      premenstrual syndrome, use of vitamin B6 has been recommended for the treatment
      of side effects of oral contraceptive (OC) use. A randomized, triple-blinded
      controlled trial of 124 women was done to evaluate the effect of taking 150 mg of
      vitamin B6 daily for 30 days on the severity of nausea, headache, vomiting,
      dizziness, depression, and irritability associated with the initiation of low
      dose (30 micrograms norgestrel and 30 micrograms ethinyl estradiol) OG use. The
      severity of the symptoms was measured on a scale from 0 to 3 (not present to
      severe), and was evaluated at one month after admission. The two treatment groups
      (vitamin B, and placebo) had comparable baseline characteristics. From admission
      to follow up, there was a decrease in the severity of all symptoms in both
      groups. There was no statistically significant difference in the reductions found
      in the vitamin B6 and the placebo groups, although reductions in the severity of
      headache and dizziness were greater in the B6 group. The decrease in the severity
      of all OC side effects can be explained more by a placebo effect than by a
      marginal pharmacological effect of the vitamin B6.

PMID- 9179459
TI  - Quantitation of vaginally administered nonoxynol-9 in premenopausal women.
AB  - A feasibility study was performed in 11 healthy nonpregnant premenopausal women
      to determine a method for collection and recovery of vaginally administered
      nonoxynol-9. We also determined if nonoxynol-9 could be quantitated in vaginal
      lavage fluid obtained 2 h after instillation of a standard precoitol dose of a
      foam formulation of nonoxynol-9. Samples were analyzed in batch using a validated
      normal phase high-performance liquid chromatography (HPLC) method. Two hours
      after instillation of one dose of Delfen Contraceptive Foam (100 mg), the
      quantity of nonoxynol-9 collected ranged from 10.8 to 67.8 mg (mean: 35.4 mg).
      This corresponds to a recovery of 11.70%, of the administered dose. Quantitation
      of vaginally administered nonoxynol-9 is both practical and feasible. These data
      represent a critical first step in the evaluation of the safety and effectiveness
      of nonoxynol-9-containing products in the prevention of sexually transmitted
      diseases.

PMID- 9179461
TI  - Anthropometrical antecedents of non-insulin dependent diabetes mellitus: an age
      and sex matched comparison study of anthropometric indices in schoolchildren from
      a high prevalence Port Moresby community.
AB  - Anthropometrical indices of 66 school children aged between 7 and 9 years from a
      community with a very high prevalence of non-insulin dependent diabetes mellitus
      (NIDDM) were compared with those of age and sex matched school children from two
      low prevalence communities. Two way analysis of variance indicated that case
      children of both sexes were significantly lighter (P < 0.001), shorter (P <
      0.001) and had lower body mass indices (BMI) (P < 0.001) than their comparisons
      but had greater triceps skinfold thickness (TSFT) (P = 0.01). These differences
      may be a reflection of subtle changes in metabolism in children destined, without
      intervention, to develop NIDDM. Anthropometrical indices may therefore have a
      role to play in the prediction of future disease. Although not the prime
      objective of the study, an analysis of available birth weights indicated a lower
      mean birth weight for the cases than the controls (difference of means, 0.35 kg;
      95% confidence intervals (CI95%). 0.13-0.57). This finding is consistent with the
      theory that impaired intrauterine growth may predispose to NIDDM.

PMID- 9179460
TI  - Renal response to volume expansion in streptozotocin-induced diabetic rats:
      influence of calcium channel blockade.
AB  - The renal response to volume expansion (VE) has been shown to be impaired in
      streptozotocin (STZ)-induced diabetes. This may contribute to the abnormal
      maintenance of fluid balance in diabetics. Since calcium channel blockade (CaCb)
      has been shown to improve renal hemodynamic and tubular functions, the present
      studies were designed to examine the ability of CaCb to enhance the response of
      kidneys from diabetic rats to a volume load. Rats were made diabetic by a single
      injection of STZ (65 mg i.p.), while the control rats received only a vehicle
      injection. Nisoldipine, a CaCb agent was given to half of the diabetic rats in a
      dose of 0.015 microgram/kg per min during the acute experiment. The left kidney
      was denervated in each rat while the right kidney remained innervated. Glomerular
      filtration rate (GFR) was elevated during VE in all of the rats except in the
      denervated kidneys of diabetic rats. Nisoldipine improved GFR in most cases.
      Urine flow increased markedly during VE. This response was enhanced by
      denervation but depressed in the diabetic rats. Nisoldipine improved the
      defective volume reflex in primarily the denervated kidneys. Changes in net
      urinary excretion of water and sodium during VE were significantly lower in the
      diabetic rats than in the control group. In the nisoldipine treated diabetic rats
      the VE induced changes in water and sodium excretion returned toward normal in
      the denervated, but not in the innervated kidneys. The data are consistent with a
      blunted volume reflex in the diabetic rats that may be improved by CaCb. Impaired
      sympatho-inhibition in diabetic rats appears to oppose the effects of VE and
      nisoldipine treatment. CaCb may contribute to the volume reflex by enhanced
      filtration as well as by reduced tubular reabsorption.

PMID- 9179462
TI  - Autoantibodies in relation to residual insulin secretion in children with IDDM.
AB  - To elucidate whether autoantibodies can be used to predict the intensity of
      autoimmune beta-cell destruction, we determined both C-peptide and autoantibodies
      (islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface
      antibodies (ICSA) and antibodies to glutamic acid decarboxylase (GADA)). In 89
      diabetic children and adolescents at diagnosis at the age of 1.2-16.6 years (mean
      +/- S.D., 9.0 +/- 4.5). Only 12/89 (14%) had no autoantibodies at diagnosis,
      while 2 patients (2%) had all 4 autoantibodies. There was a positive correlation
      between GADA and ICA (P < 0.01). At diagnosis 70% of the patients had GADA, most
      common in patients above the age of 8 years at diagnosis (P < 0.001), and with
      higher GAD-index in girls (P < 0.05). ICA was detected in 63%, most common in the
      older age groups (P = 0.04). ICSA seen in 22% of the patients as well as IAA
      (detected in 32%) were most common < 8 years of age (P = 0.06, P = 0.08,
      respectively). Children with autoantibodies had similar C-peptide levels through
      the follow up period as children of the same sex and age without antibodies,
      except for patients with ICSA alone or in combination with other autoantibodies
      who tended to have higher C-peptide levels. We conclude that not even
      combinations of autoantibodies can be used to predict beta-cell destruction in
      IDDM patients.

PMID- 9179463
TI  - Combined measurements of GAD65 and ICA512 antibodies in acute onset and slowly
      progressive IDDM.
AB  - Autoantibodies to 65 kD glutamic acid decarboxylase (GADAA) and ICA512 (ICA512AA)
      were measured by radioimmunoassays using as antigens in vitro transcribed and
      translated [35S]-methionine-labeled human GAD65 and ICA512 (IA-2). The prevalence
      of GADAA and ICA512AA in sera from 87 patients with IDDM was 39 and 23%,
      respectively. The frequency and titer of ICA512AA declined sharply within 5 years
      after the onset of IDDM. Among patients tested within 4 years after diagnosis,
      the prevalence of ICA512AA was significantly higher in acute onset IDDM than in
      slowly progressive IDDM (37 versus 6%, P < 0.025) irrespective of age, while
      there was no difference in GADAA frequency between acute onset and slowly
      progressive subtypes (51 versus 63%). A total of two patients out of 121 patients
      with NIDDM were positive for GADAA, and two other NIDDM patients, who were
      suffering from sarcoidosis, were positive for ICA512AA. Neither of the antibodies
      were positive in sera from four atypical NIDDM patients, aged < 20 years, who
      showed ketosis at onset and required insulin followed by excellent metabolic
      control with diet restriction alone. These observations suggest that ICA512AA are
      associated with rapid progression of beta cell damage in IDDM. ICA512 radioassay,
      in combination with GAD assay may provide a useful diagnostic marker for IDDM
      especially in youth.

PMID- 9179465
TI  - Reduction in body weight helps to delay the onset of diabetes even in non-obese
      with strong family history of the disease.
AB  - Of the 1200 non-diabetic offspring of non-insulin-dependent diabetic patients
      registered under the prevention programme, 262 (M:F 189:73) were available for
      analysis with greater than or equal to 4 years of follow-up. All of them had been
      prescribed a calorie restricted diet to suit their body weight, occupation and
      age, and were advised to restrict the use of refined carbohydrates and fats.
      Regular exercise was also advised. Compliance with these prescriptions was
      assessed at each follow up. At the time of analysis, it was noted that only 14.5%
      had developed diabetes in a period of 8 +/- 4.2 years even though many of them
      had impaired glucose tolerance at entry in the programme. Multiple regression
      analysis showed that initial 2 h plasma glucose, initial glucose tolerance and
      gain in body weight were strong predictors of diabetes. Weight loss occurred in
      persons who adhered to diet and exercise programmes and conversion to diabetes
      was lower in them compared to those who gained weight (P < 0.002). Although the
      rate and degree of obesity is less among Indians, it has been observed in several
      earlier studies that even a minor increase in body mass index increased the risk
      of diabetes. This study highlights the fact that measures to control weight helps
      to delay the onset of diabetes even in the non-obese despite a strong family
      history of the disorder.

PMID- 9179464
TI  - Progression of normal glucose tolerance to impaired glucose tolerance or diabetes
      in the elderly.
AB  - Factors predicting impared glucose tolerance (IGT) and diabetes (DM) were studied
      in a community-living population aged 70 years or over, with initial normal
      glucose tolerance (NGT). The baseline examinations from 1991 to 1992 included an
      oral glucose tolerance test (OGTT), physical examinations and questionnaires. The
      follow-up examinations in 1994 and 1995 comprised of an OGTT. One hundred and
      thirteen of the eligible 134 subjects, with baseline NGT, participated in the re
      examinations. Thirty six percent of these subjects progressed to IGT and 3% to
      DM. Obesity was the best predictor of IGT or DM, and central obesity was also
      associated with them. In addition, abnormal progression of glucose tolerance was
      also associated with those aged greater than 80 years, with systolic blood
      pressure greater than 160 mmHg, diastolic blood pressure greater than 80 mmHg,
      fasting blood glucose value of greater than 5.3 mmol/l, and 2 h of blood glucose
      value greater than 6.8 mmol/l.

PMID- 9179466
TI  - The association between retinopathy, nephropathy, cardiovascular disease and long
      term metabolic control in type 1 diabetes mellitus: a 5 year follow-up study of
      442 adult patients in routine care.
AB  - The aim of the present study was to examine mean HbA1c and blood pressure levels
      during a 5 year period in 442 type 1 adult diabetic patients in relation to the
      incidence and progression of retinopathy, nephropathy and to cardiovascular
      morbidity and mortality. The study showed, that in patients under routine care at
      a diabetic unit with four visits to the out-patient clinic per year, the
      intraindividual coefficient of variation for HbA1c values was 11 +/- 4% (mean +/-
      S.D.), and 7 +/- 3 and 8 +/- 2% for systolic and diastolic blood pressure,
      respectively. In 121 patients without retinopathy at entry, the 5 year incidence
      of any retinopathy was 47% (n = 57). Patients who developed retinopathy had
      higher mean HbA1c levels (P < 0.01), as well as mean systolic (P < 0.01) and
      diastolic (P < 0.05) blood pressure levels. In 123 patients with background
      retinopathy at entry, progression to severe retinopathy, i.e. clinically
      significant macular oedema, severe non-proliferative or proliferative
      retinopathy, occurred in 41% (n = 51). In those patients, the degree of metabolic
      control was worse (P < 0.001), the systolic (P < 0.05) and diastolic (P < 0.01)
      blood pressure levels were higher. The patients were stratified into four groups
      according to their urinary albumin concentration at entry: (1) normal albuminuria
      (< 12.5 mg/l), (2) borderline albuminuria (12.5-30 mg/l), (3) microalbuminuria
      (31-299 mg/l), i.c. incipient nephropathy and (4) clinical nephropathy (> or =
      300 mg/l). An increase of urinary albumin concentration in patients who had
      normoalbuminuria or borderline albuminuria at entry was associated with mean
      HbA1c levels (r = 0.24, P < 0.01 and r = 0.27, P < 0.01, respectively). No such
      association was seen in patients with microalbuminuria or clinical nephropathy at
      entry. There was no association between the increase of urinary albumin level and
      mean systolic blood pressure levels in patients who had normoalbuminuria and
      microalbuminuria at entry. In contrast, there was an association between the
      increase of urinary albumin level in patients with borderline albuminuria (r =
      0.36, P < 0.001), clinical nephropathy (r = 0.26, P < 0.05) and mean systolic
      blood pressure (P < 0.05). There was no association between the increase of
      urinary albumin levels and mean diastolic blood pressure in any of the
      albuminuria groups. As for the incidence of cardiovascular disease, renal
      insufficiency or death, the duration of diabetes (P < 0.01), urinary albumin
      concentration at entry (P < 0.001), mean systolic blood pressure (P < 0.05) and
      treatment with loop diuretics (P < 0.001) were but age, age at onset of diabetes,
      mean levels of HbA1c and diastolic blood pressure as well as treatment with beta-
      or Ca-blockers or ACE inhibitors were not related to these end-points. In
      conclusion, the present study showed that there was an association between the
      degree of metabolic control and both development and progression of retinopathy
      and progression of nephropathy of early stages in type 1 diabetic patients
      treated under routine conditions. Moreover, both the incidence and progression of
      retinopathy and progression of nephropathy at later stages were also associated
      with the long-term blood pressure levels. However, HbA1c levels were not
      associated with morbidity and mortality in cardiovascular disease or development
      of renal insufficiency.

PMID- 9179467
TI  - Incidence and severity of ketoacidosis in childhood-onset diabetes in Kuwait.
      Kuwait Diabetes Study Group.
AB  - In 1992, the diabetes registry was started in Kuwait, as part of DiaMond, a WHO
      multinational collaborative project on the incidence of childhood-onset diabetes.
      Children (243) aged below 15 years, were identified between 1 January 1992 and 31
      December 1995. Children (203) were Kuwaiti and 40 were non-Kuwaiti children but
      resident of Kuwait. For the years 1992, 1993, the annual incidence of childhood
      onset diabetes for Kuwaiti children was 15.4 per 100,000 (95% confidence interval
      12.9-19), and the degree of ascertainment was 92%. Polyuria, polydypsia, weight
      loss and nocturia were the most frequently reported symptoms; four children were
      in coma and one in shock at presentation. Nearly half of the children (49%)
      presented ketoacidosis (venous pH < 7.3 and/or plasma bicarbonate level < 18
      mmol/l). and in 53 children (23.5%) it was severe (venous pH < 7.1 and/or plasma
      bicarbonate level < 10 mmol/l). In 62 children (25.5%) it was mild to moderate
      (venous pH 7.1-7.3 and/or plasma bicarbonate level 10.1-18 mmol/l). The incidence
      of severe ketoacidosis was similar in all age groups and sexes. All children
      recovered completely without major complications and no deaths were recorded. We
      conclude that diabetic ketoacidosis is a common presentation at the onset of
      diabetes in childhood in Kuwait and attests to the lack of awareness of general
      practitioners and parents to the symptoms and signs of diabetes in childhood.

PMID- 9179468
TI  - Glycaemic control and its determinants in diabetic patients in Ethiopia.
AB  - A cross-sectional study was undertaken in which concentrations of glycated
      haemoglobins were measured in 102 diabetics seen at the outpatient clinic in
      Gondar, Ethiopia, between 26 January and 7 March, 1995. Mean HbA1, levels
      (standard deviations) were 5.35% (1.1) in non-diabetic controls, 12.0% (1.5) in
      59 insulin-dependent diabetics, and 11.0% (2.0) in 43 non-insulin dependent
      outpatients. The majority of insulin-dependent mellitus (IDDM) (78%) and non
      insulin-dependent mellitus (NIDDM) patients (77%) were poorly controlled (HbA1 >
      10.8% in IDDM, and > 9.7% in NIDDM, respectively). Multiple linear regression
      analyses revealed that HbA1 levels were significantly positively associated with
      lower body mass index, duration of diabetes, a recent history of polydipsia,
      hypertension, and low income in NIDDM individuals. Whereas in IDDM patients lower
      age (or alternatively lower age at onset) was the only significant predictor.
      Whilst 49% of the model variance was explained by the predictors in NIDDM
      diabetics, only 9% were so in IDDM patients. Current fasting blood glucose level
      was marginally significant in NIDDM patients (r = 0.29; P = 0.058), but
      insignificant in IDDM individuals. This points towards the fluctuations in blood
      glucose levels experienced by IDDM patients in a setting where insulin supply is
      unreliable. It also confirms the doubts about the usefulness of fasting blood
      glucose values as a tool for assessing metabolic control.

PMID- 9179469
TI  - Lack of association of lipoprotein (a) with coronary heart disease in Spaniard
      type 2 diabetic patients.
AB  - We tried to elucidate the possible relationship between lipoprotein (a) levels
      and coronary heart disease by assessing the presence of lipoprotein (a)
      covariates in NIDDM. We selected 41 type 2 diabetic patients with coronary heart
      disease and 82 type 2 diabetic patients free from cardiovascular disease. They
      were adjusted for age, sex and duration of diabetes. Routine chemical analysis
      was carried out using standard procedures, HbA1c by HPLC and lipoprotein (a) and
      urinary albumin excretion rate by immunonephelometry. No difference has been
      found in lipoprotein (a) levels between both groups of patients (18 [144.25]
      mg/dl in cases vs. 23 [197.25] mg/dl in controls (median [range]), Mann Whitney U
      test, P > 0.1). No association has been found between coronary heart disease and
      lipoprotein (a) levels greater than 30 mg/dl (Pearson's chi 2, P > 0.1).
      Significant and independent linear relationships have been found between the
      square root of lipoprotein (a) levels, serum creatinine and total cholesterol
      (multiple r2: 0.15, P < 0.001). Patients treated with insulin had greater square
      root of lipoprotein (a) levels, even after adjusting for serum creatinine and
      total cholesterol (5.87 +/- 0.35 vs. 4.76 +/- 0.36 (mean +/- S.E.), ANCOVA, P <
      0.05). These data do not show an association between symptomatic coronary heart
      disease and lipoprotein (a) in NIDDM. Significant and independent relationships
      have been found between this variable and serum creatinine, total cholesterol and
      insulin therapy.

PMID- 9179470
TI  - Microalbuminuria and associated clinical features among Brazilians with insulin
      dependent diabetes mellitus.
AB  - With the objective to determine the frequency of microalbuminuria,
      macroalbuminuria and the associated clinic and metabolic features among insulin
      dependent diabetes mellitus (IDDM) Brazilian patients attending at a general
      University Hospital, a total of 50 outpatients, aged 21.9 +/- 7 years with IDDM
      duration of 6.8 +/- 5.8 years were studied cross-sectionally. Urinary albumin
      excretion rate (AER) was determined in timed overnight urine samples.
      Microalbuminuria was defined when two out of three urine samples had AER ranging
      20-200 micrograms/min. Microalbuminuria was present in 12% of our patients. No
      macroalbuminuric patient was found. Among patients with diabetes duration < or =
      5 years (n = 24), 8.3% (n = 2) had microalbuminuria. Retinopathy was strongly
      associated with microalbuminuria (P = 0.004) although no proliferative
      retinopathy was noted. No difference was observed concerning FBG and HBAI between
      normo and microalbuminuria patients. Univariate analysis has revealed no
      influence of these variables in AER. Systolic blood pressure (sBP) was high in
      microalbuminuria patients and stepwise multiple regression analysis has shown
      that it was the only significant independent variable to influence AER. (R = 0.42
      r2 = 0.18 P = 0.002). In conclusion, the frequency of microalbuminuria in this
      sample of IDDM Brazilian patients was similar to other populational groups and
      was associated with retinopathy and sBP.

PMID- 9179471
TI  - The prevalence and determinants of foot ulceration in type II diabetic patients
      in a primary health care setting.
AB  - The purpose of the study was to assess the prevalence of foot (pre-)ulcers and
      their determinants in type II diabetic patients in a primary health care setting.
      Six hundred and nine patients (246 men, mean age 64.8 (range, 40-94) years,
      diabetes duration, 4.3 (0-44.9) years) from 22 general practices attended a
      regional shared care project in Amsterdam. At first visit all patients were
      examined by a podiatrist. Amputations, active fool ulcers (Wagner stage 1 or 2)
      and pre-ulcers (Wagner stage 0, hard skin with or without macerating changes)
      were recorded in 0 (0%), 11 (1.8%) and 79 (12.9%) patients, respectively. In
      multivariate logistic regression analysis, after adjustment for age and gender,
      diabetes duration, cigarette smoking, peripheral vascular disease (assessed by
      calculating ankle/brachial index), sensory neuropathy (by Semmes-Weinstein
      monofilament 5.07), dry feet and severe hammer toes were independently and
      significantly associated (pre-)ulceration. In conclusion, one of every seven type
      II diabetic patients in primary health care has a foot (pre-)ulcer. Patients at
      risk for foot ulceration can be identified by inspection and the use of simple
      instruments.

PMID- 9179472
TI  - No acute effect of high blood glucose on nerve conduction in adolescents with
      IDDM.
AB  - The aim of the present study was to evaluate the acute effect of high blood
      glucose on the motor and sensory nerve conduction in adolescents with IDDM. Four
      patients, 15-18 years old, with a history of diabetes from 5 to 9 years underwent
      repeated studies of the conduction properties in the median, peroneal, and sural
      nerves within a 10-day period. Capillary blood glucose was drawn immediately
      before and after each examination. Repeated measurements in each patient revealed
      only a small variation in the values of ten nerve conduction parameters despite
      of large differences in the blood glucose level. A multiple regression analysis
      of the data from all patients in a total of 20 measurements gave P-values between
      0.18 and 0.96, i.e. there was no correlation between any of the ten studied
      conduction parameters and the prevailing blood glucose level. This supports the
      view that nerve dysfunction is a consequence of long-term poor metabolic control
      (HbA1c) and not dependent on the acute effect of hyperglycemia in adolescents
      with IDDM.

PMID- 9179473
TI  - Islet cell antibody in mitochondrial diabetes.

PMID- 9179474
TI  - Boerhaave's syndrome: the man behind the syndrome.

PMID- 9179475
TI  - Esophageal perforation and caustic injury: approach to instrumental perforations
      of the esophagus.

PMID- 9179476
TI  - Esophageal perforation and caustic injury: management of perforated esophageal
      cancer.
AB  - Perforation of esophageal cancer is an unusual complication that most often
      results from instrumentation. The management of this condition must be
      individualized on the basis of the patient's condition and the stage of the
      cancer. For patients who are otherwise well and have localized disease, a
      standard resection is performed. Stent placement and esophageal exclusion are
      sometimes used for patients in good condition but in whom resection is not
      feasible. Supportive care alone is reserved for patients who have end-stage
      disease or are otherwise not candidates for aggressive therapy. Although the
      overall mortality rate is 50%, the risk for patients who undergo resection is
      less than 10%. This risk is similar to that found in patients undergoing elective
      resection and supports the concept that aggressive therapy should be pursued in
      highly selected patients with perforated esophageal cancers.

PMID- 9179477
TI  - Esophageal perforation and caustic injury: emergency management of caustic
      ingestion.
AB  - Diagnosis and treatment of caustic ingestion injuries remain controversial. Based
      on experience with a wide spectrum of upper gastrointestinal tract injuries from
      caustic ingestion, prospectively observed in 58 adult patients treated in a
      teaching hospital in Milan, the authors suggest an early staging of the lesions
      by endoscopy, followed by resective surgery for high-degree esophagogastric
      lesions. Ingestion of a large amount of corrosive agent results in a life
      threatening condition that requires a much more aggressive diagnostic and
      therapeutic approach than was formerly recommended. Early surgery plays a
      fundamental role in the prevention of acute hemorrhagic and perforative
      complications as well as of development of scar tissue and neoplastic stricture
      over time. The multidisciplinary approach to the management of these patients is
      underlined, stressing the need of close cooperation between a number of different
      specialists.

PMID- 9179478
TI  - Lower esophageal sphincter as an anti-reflux barrier: a review.

PMID- 9179479
TI  - Gastroesophageal sphincter: a model.
AB  - There is substantial experimental and anatomic evidence suggesting that the human
      lower esophageal sphincter is not a muscular ring but has its correlate in the
      arrangement of the so-called muscular clasps and oblique sling fibers at the
      gastroesophageal junction. We assessed the mode of action of these distinct
      muscle units in a mechanical model. The arrangement of the clasp and sling fibers
      at the gastroesophageal junction was simulated with two elastic bands placed
      perpendicularly around the gastroesophageal junction of four pig specimens. Rapid
      pullback manometry with four radially oriented pressure transducers was performed
      in each specimen. The opening pressure was determined, and three-dimensional
      pressure images were constructed based on the manometric readings. The elastic
      bands established a competent high-pressure zone at the level of the
      gastroesophageal junction. The three-dimensional pressure images matched those
      usually observed in vivo in normal human volunteers. The vector volume of the
      high-pressure zone correlated with the opening pressure while individual resting
      pressure values and length of the high-pressure zone were not sufficient to
      estimate the competence of the gastroesophageal junction in the model. This model
      supports the contention that the combined action of the clasp and sling fibers
      establishes the manometric lower esophageal sphincter in humans.

PMID- 9179480
TI  - Comparison of anterior, posterior and total fundoplication using a viscera model.
AB  - OBJECTIVE: To determine the contribution of mechanical factors to the function of
      different types of fundoplication. DESIGN AND SETTING: An experimental bench-top
      study using abattoir-sourced pig esophagus and stomach placed on a tray.
      Preliminary esophageal myotomy ensured free reflux of 'intragastric fluid'.
      INTERVENTIONS: Anterior, posterior, and total fundoplications were performed on
      each of ten sets of viscera. MAIN OUTCOME MEASURES: Lower esophageal sphincter
      pressure was measured using a conventional esophageal manometry catheter.
      Intragastric pressure was measured with a single channel intragastric manometry
      catheter, whilst the stomach was inflated with coloured water. The maximum
      intragastric pressure or the pressure measured when the fundoplication yielded to
      gastric distension was recorded. RESULTS: All three types of fundoplication
      restored adequate competence to the gastroesophageal junction, although high
      volume gastric infusions resulted in fundoplication yield in 4/10 anterior and
      4/10 posterior fundoplications. Gastric distension resulted in fundal dilatation
      and consequent compression of the adjacent esophagus. Fundoplication generated a
      median rise of 11-13.5 mmHg in lower esophageal sphincter pressure, comparable to
      pressures reported in the postoperative clinical setting. Significantly greater
      intragastric volumes and pressures were tolerated following total fundoplication.
      CONCLUSIONS: This study suggests that mechanical factors could be major
      contributors to the ability of a fundoplication to restore gastroesophageal
      competence. Anterior, posterior and total fundoplications are all effective
      procedures.

PMID- 9179481
TI  - Mechanical effect of the Angelchik prosthesis on the competency of the gastric
      cardia: pathophysiologic implications and surgical perspectives.
AB  - The Angelchik prosthesis appears to be effective in preventing gastroesophageal
      reflux, although its precise mechanism of action remains controversial. In a
      unique in vitro model, 10 freshly harvested canine esophagogastric specimens were
      tested for their ability to remain competent against challenges of intragastric
      pressure under controlled conditions of intra-abdominal pressure, longitudinal
      esophageal tension, lower esophageal sphincter pressure and overall length and
      circumference of the cardia (measure of gastric dilatation). Competency of the
      specimen was assessed by stepwise variation in the overall length of the
      sphincter, while keeping constant intraabdominal pressure (20 cm H2O),
      intragastric pressure (20 cm H2O), esophageal tension (physiologic), lower
      esophageal sphincter pressure (15 cm H2O) and degree of gastric dilatation (3
      cm). With each specimen serving as its own control, the effect produced by the
      application of an Angelchik prosthesis was evaluated. Results consistently
      demonstrated that at any lower esophageal sphincter length the percent of
      competency was increased when the prosthesis was applied (P < 0.01). The findings
      indicate that the Angelchik prosthesis controls reflux by preventing unfolding of
      the lower esophageal sphincter when challenged by intragastric pressure.

PMID- 9179482
TI  - Lower esophageal sphincter or upper gastric sphincter?

PMID- 9179483
TI  - 24-hour esophageal ambulatory manometry in patients with achalasia of the
      esophagus.
AB  - Absence of the peristaltic contractions in the esophageal body and the failure of
      the lower esophageal sphincter (LES) post-deglutitive relaxation are the major
      motor disturbances in patients with achalasia. These alterations are usually
      evidenced by means of stationary esophageal manometry, which is able to record
      changes over a brief period. The aim of this work has been to study the circadian
      esophageal motor activity of the esophageal body in patients with achalasia,
      using a non-perfused ambulatory manometry system. Ten patients with untreated
      esophageal achalasia (dilatation < or = 5 cm) had a 24-hour ambulatory esophageal
      manometry. The portable recording system consisted of a computerized data logger
      and a probe with four microtransducers 5 cm apart, the distal one being
      positioned 5 cm above the LES. A microtransducer, positioned 1 cm below the upper
      esophageal sphincter, recorded the swallow activity. Contractions frequency
      (n/min), mean amplitude (mmHg), mean duration of contraction (sec), percentage of
      contraction > 7 sec, percentage of multipeaked, repetitive and isolated
      contractions, and percentage of peristaltic and simultaneous sequences were
      evaluated and analysed during the following periods: meal-time (MT); upright
      (UP); supine night-time (NT). On the basis of the relationship with swallows the
      contraction events were classified as post-deglutitive or spontaneous. The data
      out of a group of 65 normal subjects were used as control. Student's t-test and
      Wilcoxon's rank-sum test were used for statistical analysis. Peristaltic
      sequences were detected in all patients, 27.8 +/- 12.6% of the total, and the
      19.5 +/- 11.06% of these were complete. Moreover primary peristaltic sequences
      were present in 33.1 +/- 23.4% of all peristaltic sequences. In contrast to
      current trends, our results show surprisingly the presence of peristaltic
      activity in patients with achalasia (27.9% MT; 26.9% UP; 28.1% NT). We believe
      these results are related both to the use of an ambulatory system, which allows
      24-hour monitoring and to the use of microtransducers, which are able to detect
      motor events with great accuracy. These motor events are usually not detectable
      by stationary perfused systems.

PMID- 9179484
TI  - Biological characteristics of esophageal squamous cell carcinoma associated with
      contiguous intraepithelial carcinoma.
AB  - To evaluate the biological significance of esophageal squamous cell carcinoma
      that is associated with contiguous intraepithelial carcinoma, we analyzed 95
      patients with operated esophageal carcinoma. Of these 95 patients, eight had in
      situ carcinoma. Among 87 cases in which the tumo had invaded more deeply than the
      lamina propria, there were 42 cases (48.3%) of contiguous intraepithelial
      carcinoma associated with the main tumor. The biological characteristics
      (proliferative activity of cells, as revealed by immunostaining with the Ki-67
      monoclonal antibody) of 45 tumors without contiguous intraepithelial carcinoma
      (group A) were compared with those of 42 tumors with contiguous intraepithelial
      carcinoma (group B). The more advanced was the main lesion, the lower was the
      incidence of contiguous intraepithelial carcinoma. The mean Ki-67 score of the
      main tumors in group A was 51.6% and that of the main tumors in group B was
      45.9%. The mean Ki-67 score of the main tumors in group B was very similar to
      that of the contiguous intraepithelial carcinomas that were associated with the
      main tumors (44.4%, P = 0.682). Furthermore, the mean Ki-67 score of contiguous
      intraepithelial carcinomas associated with main tumors was very similar to that
      of carcinomas in situ (41.2%, P = 0.529). From our results, it is suggested that
      tumors with high proliferative activity may be assumed to grow rapidly and, as a
      result, the region of intraepithelial carcinoma may develop into an invasive
      tumor. By contrast, tumors with low proliferative activity may grow slowly and,
      in such cases, the carcinoma may remain in the epithelium around the invasive
      tumor.

PMID- 9179485
TI  - Synchronous and metachronous carcinomas of the esophagus and head and neck.
AB  - We retrospectively analyzed the clinicopathologic findings, treatment and outcome
      of 22 patients with synchronous or metachronous carcinomas of the esophagus and
      head and neck. The patients with metachronous cancers in whom esophageal cancer
      occurred first had either an early-stage esophageal carcinoma or only one
      positive lymph node. Similarly, five of 10 patients with metachronous cancers in
      whom head and neck cancer was the first tumor had early-stage esophageal
      carcinomas. The esophageal lesion was mucosal carcinoma in four patients which
      was found by endoscopy with the iodine dye method. In the patients with
      synchronous cancers either one or both carcinomas were advanced, and the
      prognosis of these patients was poor compared with those of patients with
      metachronous carcinomas. Accordingly, endoscopic surveillance for early detection
      of metachronous lesions are encouraged.

PMID- 9179486
TI  - A patient with seven primary tumors of the upper aerodigestive tract: the process
      of field cancerization versus distant monoclonal expansion.

PMID- 9179487
TI  - Clonality of esophageal carcinomas: genetic and epigenetic events leading to loss
      of genomic stability.

PMID- 9179488
TI  - Carcinoma of the esophagus treated with radical chemoradiation 19 years after
      irradiation for recurrent breast cancer.
AB  - Prior irradiation to a site is a relative and often absolute contraindication to
      further irradiation because the tolerance dose of normal tissues is usually
      exceeded and therefore the risk of serious long-term side-effects is high. This
      case report describes radical salvage chemoradiation for an esophageal carcinoma
      in a patient who had prior high-dose neck and chest wall irradiation for the
      management of a breast cancer 19 years previously.

PMID- 9179489
TI  - What's new in pathology, pathophysiology and conservative treatment of benign
      esophageal disorders?

PMID- 9179490
TI  - Analysis of sequence patterns surrounding the translation initiation sites on
      Cyanobacterium genome using the hidden Markov model.
AB  - Sequence patterns surrounding the translation initiation sites of Cyanobacterium
      were precisely analyzed by the hidden Markov model (HMM) based on the actual
      translation initiation sites. In a previous study, 72 actual protein coding
      regions and their translation initiation sites on the genome of Synechocystis sp.
      strain PCC6803 were determined by Sazuka et al. using protein two-dimensional
      electrophoresis and microsequening. In this work, we extracted the sequence
      patterns surrounding translation initiation sites as HMM using the computer
      program YEBIS. The constructed HMM could recognize all but one translation
      initiation site. The HMM contains an AG-rich region (5.7 bp on average), as the
      Shine-Dalgarno sequence exclusively contains purines, upstream of the translation
      initiation site (-9.7 position on average) and a CT rich region (4.2 bp on
      average) just upstream from the translation initiation site. In addition, we
      found that the second amino acid (-4.5,6) could be classified into two types, one
      of which had C as their second codon while another of which has a nucleotide
      distribution relatively similar to the distribution among amino acids in the 72
      proteins. This fact corresponds well to our earlier finding that when the second
      nucleotide of the second amino acid of a translated protein was C, an initial
      methionine was processed and that otherwise the methionine was intact with high
      frequency.

PMID- 9179491
TI  - Comparison between the Escherichia coli and Bacillus subtilis genomes suggests
      that a major function of polynucleotide phosphorylase is to synthesize CDP.
AB  - Genome comparison permits identification of chromosome regions conserved during
      evolution. Bacillus subtilis and Escherichia coli are so distant that there
      exists very few conserved landmarks in their genome organisation. Analysis of the
      conserved cmk rpsA cluster pinpointed the importance of cytosine nucleotide
      metabolism. In these bacteria, mRNA turnover provides an efficient means to
      fulfil the need for CDP as a precursor of DNA synthesis. The cmk rpsA operon is
      responsible for CDP synthesis. This function is self-explained in the case of the
      cmk gene (which codes for cytidylate kinase). The case of rpsA, that codes for
      ribosomal protein S1, is more subtle. It is suggested here that S1 is a RNA
      binding protein helping polynucleotide phosphorylase (PNPase, known to be
      phylogenetically related to S1) to degrade mRNA, or helper molecule involved in
      other RNase activities. This provides an explanation for the elusive function of
      PNPase, which generates nucleoside diphosphates (not monophosphates) when
      degrading RNA. This also accounts for the discovery that the B. subtilis comR
      gene product is PNPase. This article briefly discusses the availability of
      cytosine nucleotides in eukaryotes, and suggests that they are derived from
      phospholipids turnover. Finally, the GC content of genomes is discussed in this
      new light.

PMID- 9179492
TI  - Genome analysis of Bacteroides by pulsed-field gel electrophoresis: chromosome
      sizes and restriction patterns.
AB  - The chromosomal DNAs of nine strains of seven Bacteroides species including B.
      fragilis, the type species of the genus Bacteroides, were digested with rare
      cutting restriction enzymes I-Ceu I, Not I, and Asc I and analysed by pulsed
      field gel electrophoresis. The genome sizes of B. fragilis, B. distasonis, B.
      eggerthii, B. ovatus, B. thetaiotaomicron, B. uniformis, and B. vulgatus were
      determined to be 5.3, 4.8, 4.4, 6.9, 4.8, 4.6, and 5.1 Mbp, respectively. B.
      distasonis and B. vulgatus, and also B. uniformis and B. eggerthii, showed
      similar I-Ceu I restriction profiles. I-Ceu I cut B. uniformis and B. eggerthii
      genomes into four, B. ovatus into five, B. fragilis and B. thetaiotaomicron into
      six, and B. distasonis and B. vulgatus into seven fragments. On the basis of
      genome size, restriction profile, and I-Ceu I fragment number, a phylogenetic
      tree of the Bacteroides species was proposed. This was in overall agreement with
      the previous phylogenetic tree obtained by 16S rRNA data, with the exceptions of
      B. distasonis and B. ovatus.

PMID- 9179493
TI  - Physical mapping of rice chromosomes 4 and 7 using YAC clones.
AB  - Physical maps of rice chromosomes 4 and 7 were constructed by landing yeast
      artificial chromosomes (YACs) along our high-density molecular linkage map. Using
      114 DNA markers, 258 individual YACs were located on chromosome 4. Sixty-two out
      of 258 YACs carried two or more DNA marker positions and formed 16 contigs which
      covered a total length of 17.1 cM. The other YACs were arranged to 23 positions.
      On chromosome 7, 203 individual YACs were landed on 109 DNA markers. Sixty-four
      out of 203 YACs formed 15 contigs which covered a total length of 21.8 cM and 139
      YACs were localized to 26 positions. Chromosomes 4 and 7 were covered with
      minimum tiling paths of 45 and 48 YACs, respectively. Taking the average size of
      YAC insert DNA to be 350 kb and the entire genome size to be 430 Mb, about 16-18
      Mb of each chromosome or an estimated 50% of their total lengths have been
      covered with YACs. Physical maps of these 2 chromosomes should be of great help
      in identifying useful trait genes and unraveling genetic and biological
      characteristics in rice.

PMID- 9179494
TI  - Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that is
      homozygously deleted in a lung carcinoma cell line.
AB  - Frequent chromosomal aberrations and/or losses of heterozygosity involving the
      short arm of chromosome 3 in carcinomas of the lung, kidney and other tissues
      imply that multiple putative tumor suppressor genes may be present on this
      chromosomal arm. To search for one of these genes, we determined DNA sequences in
      the genomic region at 3p22-21.3 where we had previously detected a homozygous
      deletion in a lung cancer cell line. The DNA sequence results of an about 685-kb
      region indicated that the size of the homozygously deleted segment was 638,489
      bp, in which we identified only four genes including the integrin alpha RLC and
      the trans-Golgi p230 genes, both reported previously. The predicted amino acid
      sequences of one of the two novel genes showed high homology to villin, a human
      cytoskeleton protein; those of the other gene, termed HYA22, revealed significant
      homology to YA22, a hypothetical protein predicted from DNA sequences of
      Schizosaccharomyces pombe. The computer programs HEXON or GRAIL were able to
      predict three-fourths of the exons; the smallest exon predicted by either program
      was 46 base pairs. Repetitive sequences contained in the genomic region included
      151 copies of the Alu sequence (1 copy/every 4.5 kb), 19 copies of the L1
      sequence (1 copy/every 36 kb), and 10 copies of the THE sequence.

PMID- 9179495
TI  - Localization of 16 exons to a 450-kb region involved in the autoimmune
      polyglandular disease type I (APECED) on human chromosome 21q22.3.
AB  - As a step toward identifying the pathogenic genes for autoimmune polyglandular
      disease type I (APECED) and other disorders mapped to the PFKL locus on
      chromosome 21q22.3, we have constructed a cosmid/BAC (bacterial artificial
      chromosome) contig of 450 kb covering markers D21S1460-D21S25-PFKL-D21S154 and
      performed exon trapping. We isolated 22 distinct exons including 6 exons derived
      from two known genes (PFKL and EHOC-1). Among 16 novel exons, 2 exons matched
      with human expressed sequence tags (EST) and 7 exons showed homology at predicted
      amino acid sequence level with proteins from other species. These 16 exons were
      mapped back to the cosmid contigs, 12 of which were confirmed for their
      expression by polymerase chain reaction (PCR) screening of human cDNA libraries
      of various tissues. These exon sequences and a transcript map will aid for
      isolation of corresponding genes which will be identified as candidate genes
      involved in the pathogenesis of disorders mapped to the 21q22.3 region.

PMID- 9179496
TI  - Construction and characterization of human brain cDNA libraries suitable for
      analysis of cDNA clones encoding relatively large proteins.
AB  - Analysis of proteins registered in the PIR protein database implied that most of
      relatively large proteins are related to important functions in higher
      multicellular organisms, but not many large proteins have been registered to
      date. To establish a protocol for efficient analysis of cDNA clones coding for
      large proteins, we constructed a series of strictly size-fractionated cDNA
      libraries of human brain, where the average insert sizes of cDNA clones ranged
      from 3.3 kb to 10 kb. As judged by hybridization analysis with probes derived
      from mRNAs of known sizes, the libraries with insert sizes up to 7 kb, at least,
      contained the clones corresponding to full-length transcripts in addition to
      truncated products of longer transcripts, but few chimeric clones. Using one of
      the fractionated libraries with an average insert size of 7 kb, the single-pass
      sequences from both the ends of randomly sampled clones were determined and
      sarched against DNA databases. Approximately 90% of the clones were found to be
      new with respect to their 5'-sequences while their 3'-sequences were frequently
      similar to the registered expression sequence tags. Examination of the protein
      coding capacity in an in vitro transcription/translation system showed that about
      20% of the clones direct the synthesis of proteins with apparent molecular masses
      larger than 50 kDa. The set of libraries constructed here should be very useful
      for the accumulation of sequence data on large proteins in the human brain.

PMID- 9179497
TI  - High efficiency selection of full-length cDNA by improved biotinylated cap
      trapper.
AB  - We report here an improved protocol for the preparation of full-length cDNA
      libraries that improves the previously reported method (Carninci, P., Kvam, K.,
      Kitamura, A. et al. 1996, Genomics, 137, 327-336), that allows long cDNAs to be
      cloned more efficiently. One potential disadvantage of the original biotinylated
      CAP trapper protocol is the exposure of mRNA to chemical and enzymatic attacks
      during the biotinylation of the cap structure, before the first-strand cDNA
      synthesis (and selection of full-length cDNA by biotinylated cap). Here, we show
      that the biotinylation of the cap structure is very specific and effective even
      if biotinylation is performed on the mRNA/cDNA hybrid produced by the first
      strand cDNA synthesis reaction. Consequently, mRNA remains protected from
      chemical and enzymatic degradation during the overnight biotinylation step, thus
      making it possible to select full-length cDNAs of longer average size. We herein
      report the efficiency and specificity of the new version of the protocol for cap
      structure biotinylation and capture of full-length cDNA.

PMID- 9179498
TI  - No editing of mitochondrial plasmid transcripts in mitochondria of Physarum that
      have an RNA-editing system.
AB  - Two types of RNA editing have been reported in the mitochondria of Physarum;
      extensive insertions of nucleotides and single-base substitutions. In the Ng
      strain of P. polycephalum and its derivatives, mitochondria have a specific
      plasmid (mF) that promotes fusion of mitochondria. We examined the editing of
      transcripts derived from the mF plasmid. For analysis, we selected three regions
      of the plasmid, including a DNA fragment that corresponded to missing conserved
      domains of the RNA polymerase. In contrast to the mitochondrial DNA (mtDNA), no
      RNA editing of the transcripts of the mF plasmid was detected. Our results
      suggest that the mechanism of transcription of the mitochondrial plasmid is
      independent of that of mtDNA, indicating that the plasmid has a different
      evolutionary origin from the mtDNA.

PMID- 9179499
TI  - Cloning of the promoter regions of mouse TGF-beta receptor genes by inverse PCR
      with highly overlapped primers.
AB  - In order to isolate promoters of mouse TGF-beta receptor genes, we used inverse
      PCR with highly overlapped primers corresponding to the 5' sequence of the
      receptor cDNAs. Nested primer sets only covered a 30- to 40-base region of the
      sequences. HinfI-digested and self-ligated mouse genomic DNA was used as a PCR
      template. Only one band for each receptor was seen after PCR. The amplified DNA
      fragments could direct luciferase production when the luciferase coding sequence
      was ligated after the fragments. The sequence of the fragment which correspond to
      the type II receptor showed partial homology with the promoter region of the
      human TGF-beta type II receptor. Thus, the inverse PCR with highly overlapped
      primers could be an easy way to isolate the promoter regions of many genes.

PMID- 9179500
TI  - Assignment of human membrane-type matrix metalloproteinase-2 (MT2-MMP) gene to
      16q12 by FISH and PCR-based human/rodent cell hybrid mapping panel analysis.
AB  - A new group of matrix metalloproteinase with a potential membrane domain was
      reported as membrane-type matrix metalloproteinases (MT-MMPs), and the gene
      coding for one of them, MT2-MMP was recently cloned from a human lung cDNA
      library. To predict its physiological functions by the relation to the genetic
      disorders mapped on the chromosomes, the chromosomal location of the human MT2
      MMP gene was examined by fluorescence in situ hybridization (FISH) and PCR-based
      analysis with human/rodent hybrid cell mapping panels, and it was assigned to
      16q12.

PMID- 9179501
TI  - College on problems of drug dependence meeting, Puerto Rico (June 1996) marijuana
      use and dependence.
AB  - Discoveries concerning an endogenous cannabinoid system and observations of
      dramatic increases in marijuana use among youth in the United States have fueled
      a recent increase in basic and clinical research to better understand and treat
      marijuana dependence. At the annual meeting of the College on Problems of Drug
      Dependence (Puerto Rico, 1996) a symposium 'Marijuana Use: Basic Mechanisms,
      Epidemiology, and Clinical Issues' reviewed a number of important areas of
      ongoing research that address marijuana dependence. Overviews and original
      research were presented regarding the development of dependence (preclinical and
      clinical research), motivational effects (laboratory models), the epidemiology of
      dependence and its development, clinical management of marijuana use among
      patients seeking treatment for other drugs of abuse, and treatment for adult
      marijuana dependence. This paper summarizes the symposium presentations and
      provides discussion of recent scientific developments concerning marijuana use
      and dependence.

PMID- 9179502
TI  - Estimating measurement error in alcohol dependence symptomatology: findings from
      a multisite study.
AB  - Inter-rater test-retest reliability of alcohol diagnoses and symptom ratings,
      made by means of a modified version of the Structured Clinical Interview for DSM
      III-R (SCID), were evaluated in the context of a multisite clinical trial of
      alcoholism treatment. Reliability coefficients for the subject's 'worst period'
      and the 'current period' were compared. The results show that with proper
      training, reliable diagnostic classification can be achieved across multiple
      sites. Symptom reliabilities for the current period were higher than the worst
      period. Respondents with higher discrepancies between test and retest tended to
      drink more on each drinking occasion, reported more medical detoxifications,
      changed residence more often, had lower occupational status and were rated by the
      interviewer as less attentive, motivated and intelligent. Methods to monitor and
      improve the reliability of diagnostic interviews in addiction research,
      particularly in multisite studies, are discussed in relation to the findings.

PMID- 9179503
TI  - Effects of buprenorphine and an alternative nondrug reinforcer, alone and in
      combination on smoked cocaine self-administration in monkeys.
AB  - The abuse of smoked cocaine base, also known as 'crack', continues to be a major
      public health problem and to date the success of pharmacological or behavioral
      interventions has been limited. The purpose of this study was to evaluate the
      efficacy of a behavioral (alternative reinforcer-saccharin) and pharmacological
      (0.01 mg/kg buprenorphine) treatment alone and in combination. Five adult male
      rhesus monkeys self-administered cocaine base (1.0 mg/kg/delivery) via the
      smoking/inhalation route. Each day ten smoke deliveries were available contingent
      upon completion of a chained FR (lever press), FR (inhalation response) response
      schedule during 4 hr sessions. The data were analyzed using a behavioral economic
      framework in which the lever press response requirements were varied from 64 to
      1024 to generate a demand function (consumption x FR) for cocaine under the
      following conditions: (1) buprenorphine pretreatment alone (0.01 mg/kg, i.m., 30
      min presession); (2) concurrent access to saccharin alone (0.03% wt/vol); and (3)
      buprenorphine pretreatment in the presence of concurrent access to saccharin.
      Under all conditions, increases in the lever FR resulted in significant decreases
      in smoked cocaine base deliveries. Neither buprenorphine pretreatment alone nor
      concurrent saccharin alone produced significant decreases in smoked cocaine
      deliveries; however, the combination of buprenorphine pretreatment and concurrent
      saccharin significantly decreased the mean number of smoked cocaine deliveries
      from the no treatment baseline and from the buprenorphine alone condition. These
      data suggest that the combination of pharmacotherapy and alternative reinforcers
      may be an effective treatment strategy to alter smoked cocaine self
      administration.

PMID- 9179504
TI  - Effects of past history of major depression on smoking characteristics, monoamine
      oxidase-A and -B activities and withdrawal symptoms in dependent smokers.
AB  - Past history of major depression is more common in smokers than in non-smokers.
      We have shown in a previous study that lifetime prevalence of major depression is
      higher in dependent smokers and they have lower monoamine oxidase-A and -B
      activities than non-smokers. Because several studies have found an association
      between MAO-B activity and depression we analysed data of these smokers to assess
      whether past history of major depression is associated with reduced monoamine
      oxidase activities (A and B) or not. Further, we tried to characterize smokers
      with past history of major depression and its effect on withdrawal symptoms. The
      data of 88 dependent smokers (Fagerstrom Tolerance Questionnaire score > or = 6
      and smoking > or = 20 cigarettes/day) who participated in a smoking cessation
      study were analysed. Smokers with past history of major depression but without
      current illness did not differ in demographic and smoking characteristics from
      smokers without past history of major depression. Smokers with past history of
      major depression were mainly women and had lower body mass index. Adjusted for
      gender and body mass index dependent smokers with or without past history of
      depression had similar MAO-A and MAO-B activities but smokers with past history
      of major depression had significantly lower resting plasma norepinephrine levels.
      Smokers with past history of depression had not significantly higher ratings for
      depression (Montgomery-Asberg Depression Rating Scales) and anxiety (Hamilton
      Anxiety Scales) and smoking cessation did not exacerbate these ratings (assessed
      up to 3 months) and none had depressive episode during the postcessation period
      up to one year. Past history of depression was associated with higher scores on
      'expressed sadness' and 'depressive mood'. Abstinent smokers with past history of
      depression had significantly higher ratings in one of the seven ratings of a 6
      months period for craving (day 28), anxiety (day 7) and total withdrawal symptom
      score (day 7) when compared to those who had no past history of major depression.
      It is concluded that (i) past history of major depression is more frequent in
      female smokers; (ii) smokers with past history of depression may have more
      intense withdrawal symptoms (craving and anxiety) at some time after cessation:
      and (iii) past history of depression does not affect monoamine oxidase
      activities, therefore, reduced monoamine oxidase activities found in previous
      studies are possibly characteristic features of smoking.

PMID- 9179505
TI  - Characterization of anandamide-induced tolerance: comparison to delta 9-THC
      induced interactions with dynorphinergic systems.
AB  - The endogenous ligand for the cannabinoid receptor, arachidonylethanolamide
      (anandamide), has been shown to produce antinociception using the tail-flick test
      following intrathecal administration. Anandamide was administered i.p. (40 mg kg)
      to mice four times per day for 3 days. Tolerance developed to anandamide: the
      ED50 for anandamide (i.t.) was shifted from 40 (26-61) to 139 (79-248)
      micrograms/mouse. Anandamide-tolerant mice were cross-tolerant to delta 9-THC and
      CP55,940, but not cross-tolerant to mu-, delta- or kappa- opioids, including
      dynorphins. Conversely, delta 9-THC-tolerant mice are cross-tolerant to
      anandamide, CP55,940 and kappa agonists. Our data indicate that anandamide and
      delta 9-THC differ in the mechanisms by which they induce tolerance, in
      particular the interaction with endogenous dynorphinergic systems.

PMID- 9179506
TI  - Morphine tolerance-induced modulation of [3H]glyburide binding to mouse brain and
      spinal cord.
AB  - Modulation by opioids of ATP-gated potassium channels, which regulate in part
      intracellular calcium levels, was measured by the binding of [3H]glyburide.
      Scatchard analyses generated a KD for whole brain of vehicle-pretreated mice of
      288 pM with a Bmax of 694 fmol/mg protein. In the spinal cord the KD was 0.94 nM
      and the Bmax was 184 fmol/mg protein. Acute morphine decreased the KD in brain
      and spinal cord with no change in Bmax. Morphine tolerance increased the KD in
      brain and spinal cord 2.6- and 2.9-fold, respectively, concurrent with 1.6- and
      3.4-fold increases in Bmax. Modulation by morphine of glyburide-sensitive binding
      sites may contribute at least in part to tolerance to morphine via alterations in
      intracellular calcium levels in neurons.

PMID- 9179507
TI  - Reliability of drug dependents' self-reports.
AB  - Among 936 demands for treatment by drug users in Greece in 7 months in 1994, 78
      subjects making at least two demands were identified by code numbers. The median
      time between demands was 50 days (range 2-219). The data obtained by interview at
      the first two demands were compared to estimate the reliability of the interview
      schedule of the First Treatment Demand protocol of the Pompidou Group of the
      Council of Europe. Subjects were 84.6% male, with a median age of 27 years (range
      14-43) and median duration of use 11 years (range 2-27). The primary substance of
      use was mainly heroin (88.5%). The percentage of agreement between interviews was
      highest for lifetime history of injecting (100%), urban residence (98.7%) and
      mode of use of heroin (94.3%). Percentages of agreement were close to 90% for
      most other items of socio-demographic data and drug use history, whether or not
      the correct response to the item could logically change between interviews. It is
      concluded that reliability of the data is around 90% and short-term behaviour in
      this population is rather stable. Only employment status (52.9% agreement) and
      secondary substance of abuse (25.5%) appeared to be exceptions. It is noteworthy
      that HIV and hepatitis serostatuses were reported less reliably than most other
      items.

PMID- 9179508
TI  - The effects of alcohol history on the reinforcing, subjective and psychomotor
      effects of nitrous oxide in healthy volunteers.
AB  - The purpose of this study was to characterize the reinforcing, subjective and
      psychomotor effects of nitrous oxide in healthy volunteers with different alcohol
      histories. Subjects were divided into two groups: light drinkers (n = 9) and
      moderate drinkers (n = 10). A choice procedure was used in which subjects first
      sampled placebo and a given concentration of nitrous oxide, and then chose
      between the two. Nitrous oxide concentration varied across the four-session
      experiment from 10-40%. Besides choice, subjective and psychomotor effects served
      as dependent measures. The majority of subjective effects of nitrous oxide, and
      its psychomotor-impairing effects, did not vary as a function of drinking group.
      However, a Wilcoxon rank sum test showed that the median number of times moderate
      drinkers chose nitrous oxide (three) was significantly higher than the median
      number of times light drinkers chose nitrous oxide (one). This study provides
      suggestive evidence that the reinforcing effects of nitrous oxide are modulated
      by alcohol history.

PMID- 9179509
TI  - Effects of dopaminergic drugs on food- and cocaine-maintained responding. IV:
      Continuous cocaine infusions.
AB  - The effects of cocaine (continuously infused during the session with and without
      a are-loading dose) on responding maintained under multiple fixed-ratio 30
      schedules of limited access to food and cocaine delivery (10 or 56 micrograms/kg
      per injection) were studied in nine rhesus monkeys. When responding was
      maintained by 10 micrograms/kg per injection, cocaine decreased rates of cocaine
      maintained responding in a dose-related manner while having no effect on food
      maintained responding. When responding was maintained by 56 micrograms/kg per
      injection, cocaine decreased both cocaine- and food-maintained responding. These
      results show that the effects of continuous infusions of cocaine depend upon both
      the unit dose of cocaine and the event that maintains responding. As such, the
      effects of continuous infusions of cocaine are similar to those of other, longer
      acting dopamine agonists. Such results support the development of long-acting
      agonist approaches to the pharmacotherapeutic treatment of cocaine abuse.

PMID- 9179511
TI  - Validity of the longitudinal, expert, all data procedure for psychiatric
      diagnosis in patients with psychoactive substance use disorders.
AB  - The longitudinal, expert, all data (LEAD) procedure has been employed as a
      criterion for the assessment of the procedural validity of diagnostic
      instruments. This study evaluated the procedure's concurrent, discriminant and
      predictive validity. Interview and questionnaire data obtained from 100
      individuals in a substance abuse treatment program were used to assess current
      and lifetime substance use disorders and common comorbid disorders. An
      experienced, doctoral-level clinician formulated LEAD diagnoses for each patient,
      based on an initial interview, ongoing clinical contact and the results of the
      research assessment and all available clinical records. LEAD-derived substance
      use diagnoses showed good concurrent, discriminant and predictive validity. The
      validity of comorbid diagnoses obtained using the LEAD procedure was generally
      fair to good. Comparison with diagnoses based only on the clinician's
      unstructured initial interview showed that the availability of additional data
      enhanced diagnostic validity. Diagnoses derived by a research technician using
      the Structured Clinical Interview for DSM-III-R showed validity comparable to
      that of LEAD diagnoses. To enhance its diagnostic validity, applications of the
      LEAD standard should include a structured interview. Other variations in the
      application of the LEAD standard, including a longer evaluation period, may also
      enhance its performance as a diagnostic criterion measure.

PMID- 9179510
TI  - Controlled opioid withdrawal evaluation during 72 h dose omission in
      buprenorphine-maintained patients.
AB  - Buprenorphine's clinical utility as an opioid dependence pharmacotherapy may be
      enhanced with less-than-daily dosing. This study assessed opioid withdrawal after
      an acute 72 h dose omission in buprenorphine-maintained patients (8 mg/day s.l.).
      Eight outpatients required to remain free of opioids, cocaine and benzodiazepines
      completed four double-blind, double-dummy, Latin-square ordered conditions. Test
      conditions of 8 or 16 mg s.l. buprenorphine were followed by 2 days of placebo
      dosing. Control conditions were buprenorphine maintenance (8 mg/day), to provide
      a reference for evaluation of placebo test days and naloxone administration (10
      mg 70 kg i.m.) during 8 mg buprenorphine maintenance to assess withdrawal measure
      sensitivity. Subjective measures and pupil diameter were significantly influenced
      only by naloxone. The lack of subjective symptoms and physiological signs of
      opioid withdrawal during 72 h of acute dose omission supports the feasibility of
      less-than-daily dosing at buprenorphine doses of 8 mg/day in patients who have
      demonstrated an ability to remain drug-free for an extended period.

PMID- 9179512
TI  - Cost-effectiveness of treatment for drug-abusing pregnant women.
AB  - Neonatal intensive care unit (NICU) and drug treatment costs were compared in two
      groups of pregnant drug abusing women: 100 admissions to a multidisciplinary
      treatment program and active in care at the time of delivery and 46 controls not
      entering drug treatment. Clinical measures included urine toxicology at delivery,
      infant birthweight. Apgar scores and need for and duration of NICU services. Cost
      measures included drug treatment and NICU costs. Treatment patients showed better
      clinical outcome at delivery, with less drug use and higher infant estimated
      gestational age, birthweight and Apgar scores. Infants of treatment patients were
      also less likely to require NICU services and, for those that did, had a shorter
      stay. When total cost was examined (including drug treatment), mean net savings
      for treatment subjects was $4644 per mother/infant pair. The study demonstrates
      the cost-effectiveness of treatment for pregnant drug abusing women, with savings
      in NICU costs exceeding costs of drug treatment.

PMID- 9179513
TI  - Effects of thyrotropin-releasing hormone and metoclopramide on PRL secretion in
      normally cycling and amenorrheic alcoholic women.
AB  - To assess the possible influence of alcoholism on the dopaminergic inhibitory
      control of prolactin (PRL) secretion, 10 mg of the dopaminergic antagonist
      metoclopramide (MTC), was injected i.v. in a group of eight healthy abstemious
      women (aged 28 +/- 6 (mean +/- S.E.) years) and in 16 aged-matched nondepressed
      female alcoholic subjects after 3-4 weeks of abstinence from alcohol. All normal
      controls and eight alcoholics had normal menstrual cycles and were tested in the
      early follicular phase (4-8 days), the remaining eight alcoholics were affected
      by amenorrhea (duration: 15 +/- 3 months). During the same period, all patients
      were also tested with TRH (200 micrograms in an i.v. bolus) to determine whether
      the pituitary PRL cell secretory capacity was preserved in alcoholics. The
      amenorrheic alcoholic group showed strikingly lower circulating estrogen levels
      than normally cycling groups. Similar basal PRL levels and PRL responses to TRH
      were observed in normal controls and normally cycling alcoholics, whereas basal
      and TRH-stimulated PRL levels were significantly higher in amenorrheic
      alcoholics. In contrast, the PRL response to MTC was significantly higher in
      cycling alcoholic patients than in normal controls and amenorrheic alcoholic
      subjects. However, when the statistical analysis of MTC test took into account
      the difference in estrogen levels among groups, the statistical differences in
      the PRL responses to MTC observed between normally cycling and amenorrheic
      alcoholics disappeared. These data suggest the presence of an enhanced
      dopaminergic inhibitory control of PRL secretion in 2-3 week abstinent alcoholics
      with normal menstrual cycles and normal circulating estrogen levels. In contrast,
      amenorrhea in abstinent alcoholics appears to be associated with an enhancement
      of PRL cell secretory activity.

PMID- 9179514
TI  - Family structure, personality, drinking, smoking and illicit drug use: a study of
      UK teenagers.
AB  - Data from a survey of 7722 15-16 year old school students in the United Kingdom
      were used to examine relationships between family structure and using alcohol,
      tobacco and illicit drugs. Respondents living with both parents were
      significantly less likely to participate in all of these, with girls more
      affected, particularly as regards cigarette smoking and illicit drugs. For other
      families, it made little further difference whether the mother, the father or
      both were absent. The effects were reduced on controlling four other variables.
      The latter were: psychological symptoms, social support, involvement in hobbies
      and reading, and engagement in behaviours such as riding mopeds, going out with
      friends, aggression and delinquency. It is suggested that these variables may
      mediate the effects of family structure.

PMID- 9179515
TI  - Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid
      addicts.
AB  - In a study evaluating naltrexone with either an intensive psychosocial protocol
      or standard community treatment for opioid dependence, 13 of 81 subjects
      overdosed within a 12-month period of study participation. There were four
      fatalities, one of which was a suicide. Among the nine nonfatal overdoses, there
      were four suicide attempts. Characteristics of subjects and naltrexone-taking are
      described.

PMID- 9179517
TI  - Utility of the AUDIT for identification of hazardous or harmful drinking in drug
      dependent patients.
AB  - We evaluated the psychometric properties of the alcohol use disorders
      identification test (AUDIT), a ten-item screening test for identification of
      hazardous drinkers, in a sample of 82 patients with DSM-III-R drug dependence.
      AUDIT showed good internal consistency (alpha = 0.94) and a unitary factor
      structure. Receiver operating characteristics analysis showed the AUDIT to be
      comparable to the Michigan alcoholism screening test (MAST) in identifying
      individuals with a current alcohol use disorder and superior to the MAST for
      those who are hazardous drinkers. In this patient sample, AUDIT performed well at
      the recommended cut-off score of > or = 8. We recommend use of the AUDIT for
      identification of hazardous and harmful drinking among individuals with a drug
      use disorder.

PMID- 9179516
TI  - Alprazolam-reinforced medication use in outpatients with anxiety.
AB  - The reinforcing effects of alprazolam were investigated in 14 patients who had
      generalized anxiety or panic disorder, but were not current users/abusers of
      other psychoactive substances. Using a double-blind outpatient choice procedure,
      color-coded alprazolam (0.5 mg) and placebo capsules were provided to patients
      for use 'as needed' in the treatment of anxiety symptoms. Comparisons of
      alprazolam and placebo during a 2 week sampling period in which placebo and
      alprazolam were available sequentially revealed no significant differences on
      measures of medication usage or anxiety levels, although alprazolam did increase
      subjective ratings of drug effects side effects. During a 4 week choice period,
      alprazolam was strongly preferred over placebo in 11 out of 14 patients
      indicating that alprazolam functioned as a reinforcer. Medication usage ranged
      from zero to 4.0 mg alprazolam in a day. Variations in daily medication-use were
      positively correlated with anxiety level fluctuations for a majority of patients.
      For a majority of patients, the results indicate that alprazolam functioned as a
      reinforcer without accompanying signs of abuse or addiction.

PMID- 9179518
TI  - Behavioral self-regulation: correlates and 2 year follow-ups for boys at risk for
      substance abuse.
AB  - This investigation demonstrated the heuristic construct of behavioral self
      regulation (BSR) as a salient component of the liability to substance abuse.
      Three dimensions of childhood behaviour were employed to create a dimensional
      model of BSR: inattention, impulsivity/hyperactivity and aggressivity. Multiple
      measures and multiple informants were employed to develop indices of the three
      traits in a sample of 10-12 year old sons of substance abusing fathers (high risk
      (HR); n = 180) and normal controls (low average risk (LAR); n = 200). Informants
      included mothers, boys and their teachers. The results confirmed the presence of
      a first-order latent trait of BSR. HR boys had significantly higher scores on BSR
      than LAR boys. Concurrent validity of the BSR trait scores was supported by
      significant associations with measures of family dysfunction, deviant peer
      affiliations and poor school performance. These latter problems are commonly
      prodromal to substance abuse. Predictive validity of the BSR trait baseline
      scores (age 10-12 years) was supported at 2 year follow-up by significant
      associations of BSR scores with magnitude of deviant peer affiliations; trends
      toward significance were found for family dysfunction and poor school
      performance. Taken together, these results confirm and extend previous findings
      which indicate that poor BSR is prodromal to substance abuse.

PMID- 9179519
TI  - Sensitivity and specificity to amphetamine of a French version of the 49-item
      form of the addiction research center inventory.
AB  - The main metrological characteristics of a French version of the 49-item
      addiction research center inventory (ARCI) were evaluated using data collected in
      three controlled studies in healthy subjects. An analysis of variance showed no
      study effect, so the three studies were pooled. The test-retest reliability
      coefficients after placebo evaluated by a Spearman rank correlation test were
      0.64 (P < 0.0001) for subscale A, 0.49 (P < 0.0001) for subscale BG, 0.55 (P <
      0.0001) for MBG, 0.58 (P < 0.0001) for PCAG and 0.27 for LSD (not significant).
      Using the same test, the test-retest reliability coefficients after amphetamine
      were 0.73 (P < 0.0001) for subscale A, 0.61 (P < 0.0001) for subscale BG, 0.71 (P
      < 0.0001) for MBG, 0.46 (P < 0.0001) for PCAG and 0.66 for LSD (P < 0.0001). In
      order to assess the predictive validity of the translated questionnaire, areas
      under curves were calculated from the ROC diagrams for the three scores,
      amphetamine (A), benzedrine group (BG) and morphine benzedrine group (MBG). Two
      criteria validity were used: the desire to take amphetamine another time and the
      discrimination of the allocated treatment (amphetamine or placebo). The
      calculated areas under curves indicated a good capacity of prediction of the
      three ARCI subscales (A, BG, MBG) for both criteria.

PMID- 9179520
TI  - Sequence of drug use among serious drug users: typical vs atypical progression.
AB  - Sequence of drug use was examined in a secondary analysis of two samples of
      serious drug users: one of 152 men and one of 133 women. The proportions of drug
      users following specified patterns of drug use onset were compared to proportions
      obtained in previous research in samples of high school youth, and serious drug
      users. The serious drug users were substantially different from high school
      samples in their progression of drug use. The serious drug users were less likely
      to follow the typical sequence identified in previous studies (alcohol, then
      marijuana, followed by other illicit drugs). They were more likely to have used
      marijuana before using alcohol, and more likely to have used other illicit drugs
      before using marijuana. We also found that atypical sequencing was associated
      with earlier initiation of the use of illicit drugs other than marijuana and
      greater lifetime drug involvement. These findings suggest that for a large number
      of serious drug users, marijuana does not play the role of a 'gateway drug'. We
      conclude that prevention efforts which focus on alcohol and marijuana may be of
      limited effectiveness for youth who are at risk for serious drug abuse.

PMID- 9179521
TI  - Antagonism of the response rate-decreasing effects of meperidine and morphine by
      beta-funaltrexamine and naltrexone in squirrel monkeys.
AB  - Level pressing by squirrel monkeys was maintained under a fixed-ratio 30 schedule
      of food presentation. The response rate-decreasing effects of meperidine and
      morphine were examined alone and in combination with several doses of the
      irreversible, mu-selective opioid antagonist beta-funaltrexamine and the
      reversible, opioid antagonist naltrexone. beta-Funaltrexamine alone decreased
      response rates to greater than 50% of control at all doses in two of the four
      monkeys and at the highest dose in one monkey. In the monkeys in which beta
      funaltrexamine decreased rates, beta-funaltrexamine either did not shift the
      meperidine or the morphine dose-effect curve or it shifted these curves to the
      left. In the monkeys in which beta-funaltrexamine alone did not decrease rates,
      it shifted the meperidine and the morphine dose-effect curves to the right.
      Naltrexone also shifted both the meperidine and morphine dose-effect curves
      rightward, although not in a dose-dependent manner. These data suggest that the
      rate-decreasing effects of meperidine and morphine in squirrel monkeys are
      altered by beta-funaltrexamine and naltrexone in a similar manner, providing
      additional evidence that the rate-decreasing effects of both meperidine and
      morphine are mediated by mu-opioid receptors.

PMID- 9179522
TI  - Nicotine, caffeine and alcohol use in high- and low-dose benzodiazepine users.
AB  - Cigarette smoking, coffee and alcohol use were investigated prospectively in 37
      high-dose benzodiazepine (BZD) regular users (HDRU), 87 low-dose BZD regular
      users (LDRU), 50 low-dose BZD occasional users (LDOU) and in 37 non-BZD users
      (control subjects). The frequency of smokers was significantly greater in the
      HDRU than in the other three groups studied. Also, the HDRU consumed a
      significantly greater number of cigarettes and dose of caffeine per day than the
      other subjects investigated. Also, alcohol dependence was significantly more
      frequent in the HDRU. Regression analysis showed a significant positive
      correlation between the BZD dose and both the cigarettes and the caffeine
      consumed per day. The findings suggest that BZD should be prescribed with caution
      in individuals who are heavy smokers or are consuming large amounts of coffee and
      alcohol.

PMID- 9179523
TI  - Peppers and pain. The promise of capsaicin.
AB  - Capsaicin, the most pungent ingredient in red peppers, has been used for
      centuries to remedy pain. Recently, its role has come under reinvestigation due
      to evidence that the drug acts selectively on a subpopulation of primary sensory
      neurons with a nociceptive function. These neurons, besides generating pain
      sensations, participate through an antidromic activation in the process known as
      neurogenic inflammation. The first exposure to capsaicin intensely activates
      these neurons in both senses (orthodromic: pain sensation; antidromic: local
      reddening, oedema etc.). After the first exposure, the neurons become insensitive
      to all further stimulation (including capsaicin itself). This evidence led to the
      proposal of capsaicin as a prototype of an agent producing selective analgesia.
      This perspective is radically different from previous 'folk medicine' cures,
      where the drug was used as a counter-irritating agent (i.e. for muscular pain).
      The new concept requires that capsaicin be repeatedly applied on the painful area
      to obtain the desensitisation of the sensory neurons. Following this idea,
      capsaicin has been used successfully in controlling pain in postherpetic
      neuralgia, diabetic neuropathy and other conditions of neuropathic pain.
      Furthermore, evidence indicates that capsaicin could also control the pain of
      osteoarthritis. Finally, repeated applications of the drug to the nasal mucosa
      result in the prevention of cluster headache attacks. On the basis of this
      evidence, capsaicin appears to be a promising prototype for obtaining selective
      analgesia in localised pain syndromes.

PMID- 9179524
TI  - Drug treatment of schizophrenia in the 1990s. Achievements and future
      possibilities in optimising outcomes.
AB  - The current state of the art of the pharmacological treatment of schizophrenia,
      and a review of the latest findings in antipsychotic drug development are
      presented. A first step in optimising treatment is an increase in the awareness
      and implementation of existing treatment standards. The introduction of clozapine
      challenges the view that all antipsychotics are of similar efficacy; the drug has
      an established superiority over some of the traditional antipsychotics in
      treatment-resistant patients. Newer agents such as zotepine, risperidone,
      quetiapine, olanzapine and sertindole, which have a lower risk of producing
      extrapyramidal motor symptoms, have been developed in the wake of clozapine.
      While it is still common to switch nonresponding patients to an antipsychotic of
      a different chemical class, clozapine treatment remains the only strategy based
      on sound scientific evidence in these patients, although the novel antipsychotics
      give rise to hope. Alternatively, combination treatment with benzodiazepines,
      lithium or an anticonvulsant has been employed. If treatment with a depot
      antipsychotic is planned, it is advisable to start a patient on the oral form of
      the same drug in order to obtain dose requirements and tolerability information
      of the drug in that patient. Long term maintenance therapy is crucial and
      continuous monitoring for the development of adverse effects essential.

PMID- 9179525
TI  - Lactulose, disaccharides and colonic flora. Clinical consequences.
AB  - Lactulose is one of the most frequently utilised agents in the treatment of
      constipation and hepatic encephalopathy because of its efficacy and good safety
      profile. The key to understanding the possible modes of action by which lactulose
      achieves its therapeutic effects in these disorders lies in certain
      pharmacological phenomena: (a) lactulose is a synthetic disaccharide that does
      not occur naturally; (b) there is no disaccharidase on the microvillus membrane
      of enterocytes in the human small intestine that hydrolyses lactulose; and (c)
      lactulose is not absorbed from the small intestine. Thus, the primary site of
      action is the colon in which lactulose is readily fermented by the colonic
      bacterial flora with the production of short-chain fatty acids and various gases.
      The purpose of this review is to focus on some pertinent basic aspects of the
      clinical pharmacology of lactulose and to discuss the possible mechanisms by
      which lactulose benefits patients with constipation and hepatic encephalopathy.

PMID- 9179527
TI  - Current guidelines for the management of aggressive non-Hodgkin's lymphoma.
AB  - The prognosis of aggressive non-Hodgkin's lymphoma (NHL) has improved greatly
      during recent years with the use of combination chemotherapy. Planning the
      treatment must take into consideration the patient's age, performance status,
      histological subtype and disease extent and severity. Recently, a 4-part
      International Prognostic Index (IPI), based on 5 prognostic factors, has
      permitted the allocation of patients with NHL in 2 well defined prognostic
      groups: good prognosis (low and low-intermediate risk) and poor prognosis
      (intermediate-high and high risk). Conventional chemotherapy with CHOP (a
      chemotherapeutic regimen consisting of a combination of cyclophosphamide,
      doxorubicin, vincristine and prednisone) or other equivalent third-generation
      regimens may be considered the standard treatment for the good prognosis group.
      In the poor prognosis group the probability of long term survival is less than
      40% with conventional chemotherapy. Therefore, an early intensification with high
      dose therapy following peripheral stem cell transplantation (PSCT) should be
      considered in the setting of randomised trials. Localised stage disease, defined
      as stages I-IE and II-IIE without adverse prognostic factors, has a very good
      prognosis with a long term survival exceeding 80% using brief conventional
      chemotherapy regimens plus involved field radiotherapy. Refractory or relapsing
      patients after the drugs of first choice are given who subsequently respond to
      salvage chemotherapy should be enrolled for a course of high dose consolidation
      chemotherapy followed by PSCT. Elderly patients without severe organ dysfunction
      can take advantage from specifically devised chemotherapy regimens, with a
      response rate similar to that of younger patients. However, despite major
      advances in the treatment of aggressive NHL, additional clinical trials are
      required to enable the clinician to define the best therapeutic programmes to
      treat patients with this disorder.

PMID- 9179526
TI  - Pharmacological approaches to the prevention of autoimmune diabetes.
AB  - Insulin-dependent (type I) diabetes mellitus (IDDM) is the consequence of a
      chronic cell-mediated immune attack upon the insulin-producing beta-cells.
      Progressive insulinopenia is characteristic of individuals who eventually develop
      IDDM. Autoimmunity develops because of a failure in self-nonself discrimination.
      Autoimmunity is usually detected when autoantibodies are present in the patient's
      serum. However, autoantibodies are not synonymous with disease, as many
      autoantibody-positive individuals show no evidence of clinical disease. Studies
      initiated in the early 1980s demonstrated that short term remission from IDDM
      could be induced or lengthened with immunosuppressive therapy. However, no long
      term remissions were achieved. Current prevention strategies use a combination of
      autoantibody marker testing and beta-cell function testing to identify
      individuals with 'prediabetes'. The most useful autoantibodies for prediabetes
      screening include islet cell autoantibodies, insulin autoantibodies, glutamic
      acid decarboxylase autoantibodies and IA-2 autoantibodies. Immunointervention
      techniques have focused on protecting beta-cells from oxidative damage and
      developing tolerance to beta-cell autoantigens. Environmental manipulation may
      also be of benefit but its effectiveness is unproven. The pharmacist of the
      future may be involved in dispensing autoantigens, cytokines, anti-cytokine
      antibodies, anti-cytokine receptor antibodies, vaccines or viral vectors for gene
      therapy in the prevention of IDDM.

PMID- 9179528
TI  - Clarithromycin. A review of its efficacy in the treatment of respiratory tract
      infections in immunocompetent patients.
AB  - Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro
      and effective in vivo against the major pathogens responsible for respiratory
      tract infections in immunocompetent patients. It is highly active in vitro
      against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma
      pneumoniae and Legionella spp.) and has similar activity to other macrolides
      against Staphylococcus aureus. Streptococcus pyogenes, Moraxella catarrhalis and
      Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately
      susceptible to clarithromycin alone, but activity is enhanced when the parent
      drug and metabolite are combined in vitro. Absorption of clarithromycin is
      unaffected by food. More than half of an oral dose is systemically available as
      the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are
      nonlinear, with plasma concentrations increasing in more than proportion to the
      dosage. First-pass metabolism results in the rapid appearance of the active
      metabolite 14-hydroxy-clarithromycin in plasma. Clarithromycin and its active
      metabolite are found in greater concentrations in the tissues and fluids of the
      respiratory tract than in plasma. Dosage adjustments are required for patients
      with severe renal failure, but not for elderly patients or those with hepatic
      impairment. Drug interactions related to the cytochrome P450 system may occur
      with clarithromycin use. In addition to the standard immediate-release
      formulation for administration twice daily, a modified-release formulation of
      clarithromycin is now available for use once daily. In dosages of 500 to 1000
      mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of
      community-acquired upper and lower respiratory tract infections in hospital and
      community settings as beta-lactam agents (with or without a beta-lactamase
      inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar
      in efficacy to azithromycin in comparative studies and is as effective as and
      better tolerated than erythromycin. Adverse events are primarily gastrointestinal
      in nature, but result in fewer withdrawals from therapy than are seen with
      erythromycin. Clarithromycin provides similar clinical and bacteriological
      efficacy to that seen with beta-lactam agents, cephalosporins and other
      macrolides. It offers a cost-saving alternative to intravenous erythromycin use
      in US hospitals and is available in both once-daily and twice-daily formulations.
      The spectrum of activity of clarithromycin against common and emerging
      respiratory tract pathogens may make it suitable for use in the community as
      empirical therapy of respiratory tract infections in both children and adults.

PMID- 9179530
TI  - Acamprosate. A review of its pharmacology and clinical potential in the
      management of alcohol dependence after detoxification.
AB  - Acamprosate (calcium acetylhomotaurinate), a synthetic compound with a similar
      chemical structure to that of gamma-aminobutyric acid, is thought to act via
      several mechanisms affecting multiple neurotransmitter systems; inhibition of
      neuronal hyperexcitability by antagonism of excitatory amino acid activity and
      reduction of calcium ion fluxes has been suggested as its predominant mechanism
      of action. The drug is the first agent specifically designed to maintain
      abstinence in alcohol (ethanol)-dependent patients after detoxification.
      Voluntary oral ethanol consumption in ethanol-preferring or ethanol-dependent
      rats is dose-dependently reduced by acamprosate: total fluid intake and food
      consumption are not affected. The drug does not potentiate the acute or chronic
      toxic effects of ethanol and has no hypnotic, antidepressant, anxiolytic or
      muscle-relaxant effects in animals. There is no evidence of abuse potential with
      acamprosate. Oral acamprosate 1.3 or 2 g/day in 3 divided doses administered for
      3 to 12 months to alcohol-dependent patients after detoxification was more
      effective than placebo in preventing alcohol relapse according to abstinence
      rates, duration of abstinence, gamma-glutamyl transferase levels and/or a variety
      of other clinical or biological end-points. Concomitant psychosocial/behavioural
      therapies were used in some trials. Compared with those with placebo, the
      superior abstinence rates and durations of abstinence with acamprosate were
      maintained during 6- to 12-month post-treatment follow-up periods, and greater
      abstinence rates with acamprosate were confirmed in a pooled analysis of data
      from 11 randomised placebo-controlled trials involving a total of 3338 patients
      with alcohol dependence. The efficacy of acamprosate appears to be dose dependent
      and enhanced by the addition of disulfiram. Acamprosate was generally well
      tolerated in placebo-controlled trials. The most common adverse events were
      gastrointestinal (especially diarrhoea) or dermatological and were mostly mild
      and transient. The percentage of patient withdrawals because of adverse events
      was similar in acamprosate and placebo groups. No trials have compared the
      efficacy or tolerability of acamprosate with those of other treatment approaches
      (including opiate antagonists or selective serotonin reuptake inhibitors) aimed
      at maintaining abstinence in detoxified alcohol-dependent patients. Thus,
      acamprosate, as an adjunct to psychosocial/behavioural therapies, represents a
      novel advance for the management of alcohol-dependent patients in the
      postdetoxification period. Longer term and comparative trials with other active
      therapies are required to confirm these promising results.

PMID- 9179529
TI  - Fludarabine. An update of its pharmacology and use in the treatment of
      haematological malignancies.
AB  - Fludarabine is an antineoplastic agent which has been studied in patients with a
      variety of lymphoproliferative malignancies. Clinical evidence from comparative
      studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at
      least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP
      (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated
      or chemotherapy-naive patients and significantly more effective than chlorambucil
      in terms of response rate and duration and survival in chemotherapy-naive
      patients. Promising results have also been reported with fludarabine-based
      combination therapy in the treatment of patients with CLL. In addition,
      sequential therapy with fludarabine and cytarabine has demonstrated good efficacy
      in the treatment of acute leukaemias, as has fludarabine monotherapy and
      combination therapy in low grade non-Hodgkin's lymphoma. A favourable
      cytoreductive response has been reported in patients with lymphoplasmacytoid
      lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL
      of T cell origin or prolymphocytic leukaemia. Recent data also support the use of
      fludarabine, either as a component of a nonmyeloablative conditioning regimen or
      in the attainment of minimal residual disease, in patients undergoing peripheral
      blood stem cell or bone marrow transplantation. The tolerability profile of
      fludarabine is similar to that of CAP, with the most common adverse events being
      granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and
      nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP
      although the development of immune cytopenias is more frequent with fludarabine.
      Severe neurotoxicity has been reported with fludarabine but this is mostly
      confined to the use of high doses. Clinical experience therefore indicates that
      fludarabine is an effective and generally well-tolerated antineoplastic agent for
      the second-line treatment of advanced CLL. Recent data from comparative studies
      also support the earlier use of fludarabine in the treatment of chemotherapy
      naive patients with CLL. Furthermore, results of available studies are
      increasingly highlighting an important future role for fludarabine in the
      treatment of acute leukaemias and low grade NHL and possibly other
      lymphoproliferative disorders, particularly when used as a component of
      combination chemotherapy.

PMID- 9179533
TI  - Evaluation of two markers of cell maturation and proliferation in cultured
      amniotic cells of trisomic 18 fetuses at the 15th week of gestation.
AB  - Intensive studies have been conducted so far on biochemical markers available for
      screening of chromosome defects in obstetrical monitoring. In this paper we
      report further data on two protein phosphatases: alkaline phosphatase (a marker
      of cell maturation) and phosphotyrosine phosphatase (a marker of cell
      proliferation) assayed in cultured amniotic cells from fetuses with trisomy 18 at
      15 weeks of gestation. Comparison with normal fetal cells showed a different
      behaviour for each enzyme: alkaline phosphatase was very significantly lowered
      while phosphotyrosine phosphatase remained a normal levels. These results provide
      a further enlargement of the field of biochemical markers used in the screening
      tests of trisomy 18.

PMID- 9179531
TI  - Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and
      clinical efficacy in the management of HIV infection.
AB  - Zalcitabine is a dideoxynucleoside antiretroviral agent that is phosphorylated to
      the active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) within both
      uninfected and HIV-infected cells. At therapeutic concentrations, ddCTP inhibits
      HIV replication by inhibiting the enzyme reverse transcriptase and terminating
      elongation of the proviral DNA chain. The results of 3 large pivotal trials
      comparing zidovudine monotherapy with combination therapy have now clearly
      established that zalcitabine plus zidovudine combination with an improvement in
      viral load and CD4+ cell count compared with zidovudine monotherapy. More
      recently, clinical end-point and surrogate marker data have established the
      efficacy of zalcitabine in combination with the protease inhibitor saquinavir in
      zidovudine-experienced patients. Other studies have demonstrated the utility of
      zalcitabine in combination with ritonavir and the nucleoside analogue lamivudine.
      Importantly, early use of zalcitabine in the treatment sequence does not appear
      to limit the therapeutic efficacy of subsequent therapy with other nucleoside
      analogues such as lamivudine. Peripheral neuropathy is the most frequent dose
      limiting adverse effect associated with zalcitabine therapy and is generally
      reversible on discontinuation of treatment. Stomatitis and mouth ulcers may occur
      frequently with zalcitabine therapy but tend to resolve with continuing
      treatment. Haematological toxicity, which is a common adverse effect associated
      with zidovudine, is reported infrequently with zalcitabine. Overall, combination
      therapy with zalcitabine plus zidovudine or saquinavir has been shown to have a
      tolerability profile comparable to that of either agent alone, although treatment
      with zidovudine plus zalcitabine was associated with a significant increase in
      the incidence of haematological toxicity compared with zidovudine monotherapy in
      one study. Therefore, current data suggest that zalcitabine is a useful
      antiretroviral agent for inclusion as a component of initial double combination
      therapy with zidovudine or as part of triple combination therapy including
      zidovudine plus a protease inhibitor in the management of patients with HIV
      infection.

PMID- 9179534
TI  - Fetal and maternal plasma insulin-like growth factors and binding proteins in
      pregnancies with appropriate or retarded fetal growth.
AB  - A prospective observational study of 104 women was performed to study whether the
      insulin-like growth factor (IGF) system in pregnancy before labour is associated
      with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal
      diagnosis or at elective caesarean delivery and a maternal sample was also
      obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by
      RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference
      and birthweight and were subdivided into fetal growth retardation (FGR, n = 20)
      and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal
      outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65,
      P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing
      gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1
      was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA
      fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP
      1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not
      support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR.
      Elevated binding proteins may lead to a relative deficiency of free IGF but
      changes in binding proteins may be secondary to metabolic changes. In FGR,
      maternal IGF-1 was low with high binding proteins, so this system may be
      important in controlling placental transfer.

PMID- 9179535
TI  - Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants:
      has the dose been too low? The NICHD Neonatal Research Network.
AB  - OBJECTIVE: Inconsistent effects of vitamin A supplementation on prevention of
      bronchopulmonary dysplasia have been reported. Meta-analysis of these reports
      resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia
      associated with vitamin A supplementation. Effective dosage regimens or serum
      retinol concentrations have not been determined in previous reports. The purpose
      of this pilot study was to define a vitamin A regimen that produces serum retinol
      concentrations of 25-55 micrograms/dl. STUDY DESIGN: In this three-phase study,
      91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was
      administered three times/week for 4 weeks at an average daily dose of 986-2143
      IU/day. Physical examinations were performed and serum retinol specimens were
      collected weekly to assess clinical signs of toxicity. RESULTS: The majority of
      serum retinol concentrations remained < 25 micrograms/dl until an intramuscular
      vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of
      toxicity were associated with the higher dosage and higher serum concentrations
      of vitamin A. CONCLUSION: A large clinical trial of vitamin A supplementation
      with 5000 IU/dose three times/week (25-114% more than the dose used in the three
      published clinical trials) is needed to assess whether vitamin A supplementation
      safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight
      infants.

PMID- 9179532
TI  - Lisinopril. A review of its pharmacology and use in the management of the
      complications of diabetes mellitus.
AB  - Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal
      function in hypertensive patients with non-insulin-dependent or insulin-dependent
      diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without
      adversely affecting glycaemic control or lipid profiles. On available evidence,
      renoprotective effects appear to be greater with lisinopril than with comparator
      calcium channel blockers, diuretics and beta-blockers, despite similar
      antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of
      Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also
      renoprotective in normotensive patients with IDDM and microalbuminuria. The
      effect in normotensive patients with normoalbuminuria was smaller than in those
      with microalbuminuria, and no conclusions can yet be made about its use in
      patients with normoalbuminuria. In complications other than nephropathy,
      lisinopril has shown some benefit. Progression to retinopathy was slowed during 2
      years' lisinopril therapy in the EUCLID study. Although not yet fully published,
      these results provide the most convincing evidence to date for an effect of an
      ACE inhibitor in retinopathy. The drug may also improve neurological function,
      but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial
      indicates that lisinopril reduces 6-week mortality rates in diabetic patients
      when begun as early treatment after an acute myocardial infarction. The
      tolerability profile of lisinopril is typical of ACE inhibitors and appears to be
      similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a
      similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In
      addition, the GISSI-3 study indicates that the incidence of persistent
      hypotension and renal dysfunction is increased with lisinopril in general, but
      the presence of diabetes does not appear to confer additional risk of these
      events in diabetic patients with acute myocardial infarction receiving
      lisinopril. In summary, lisinopril lowers blood pressure and produces a
      renoprotective effect in patients with IDDM and NIDDM without detriment to
      glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should
      thus be viewed as a first-line agent for reducing blood pressure and preventing
      or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM
      and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril,
      provides new data supporting an additional place in managing normotensive
      patients with microalbuminuria and IDDM. These findings, together with some
      evidence for an effect of lisinopril in delaying progression of retinopathy and
      in reducing mortality, suggest a broader role for the drug in managing diabetic
      vascular complications.

PMID- 9179536
TI  - Ultrasonographic analysis of sucking behavior of newborn infants: the driving
      force of sucking pressure.
AB  - The sucking behaviors of 15 low-risk full-term newborns were observed with
      ultrasonography and a special device directly measuring sucking pressure. In this
      study, the sequential changes in the movement of a tongue and other intra-oral
      structures and the sequential changes of the sucking pressure were successfully
      examined simultaneously. It was indicated that sucking pressure could be
      generated by sequential changes of an intra-oral volume caused by a peristalsis
      of the tongue in the sucking behavior.

PMID- 9179537
TI  - Standards for the quantification of serial changes in Doppler resistance indices
      from the umbilical arteries.
AB  - Two-hundred- and-seventy-four low-risk pregnancies underwent serial ultrasound
      examinations in order to determine the mean and standard deviation of the change
      in umbilical artery resistance indices with advancing gestation. There is an
      almost constant rate of reduction in the A/B ratio and the Pulsatility index over
      time from 28 weeks gestation until term. By calculating the standard deviation
      score of such changes, these reference ranges allow the change in the A/B ratio
      and Pulsatility index to be quantified. Such appropriately derived standards
      permits the further investigation of the evolution of abnormalities of feto
      placental perfusion with regards to perinatal outcome.

PMID- 9179538
TI  - Regression of polyneural innervation in the human psoas muscle.
AB  - During the early stages of mammalian ontogeny muscle fibres are innervated by
      more than one axon. This polyneural innervation is replaced by mononeural
      innervation in the course of development. The regression of polyneural
      innervation in the psoas muscle in the human is the topic of the present study.
      Innervation patterns were studied in fetuses from 15 1/2 weeks of post menstrual
      age (PMA) and in babies until 80 weeks PMA (40 weeks after term age) and compared
      to data from two adults. Motor endplates were stained by a combined
      acetylcholinesterase stain. Innervation patterns and motor endplate morphology
      were studied and the sizes of endplates were measured. As a main result of our
      study polyneural innervation of the psoas muscle remains at a level of about 2
      endings per endplate (range 1-5 terminals) until 18-25 weeks PMA and decreases
      thereafter. From 52 weeks PMA (12 weeks post term) onwards, muscle fibres are
      predominantly mononeurally innervated. During development the morphology of the
      terminal patterns of the nerve endings becomes more complex and the size of
      endplates increases, implying that the adult pattern of muscle innervation is
      reached at the age at which a major functional transformation in the
      neurobehavioural repertoire occurs (i.e. the end of the second and the beginning
      of the third month.

PMID- 9179539
TI  - Cerebral metabolic rate for glucose after neonatal hypoglycaemia.
AB  - OBJECTIVE: We studied the effect of neonatal hypoglycaemia on the local cerebral
      metabolic rate for glucose (LCMRglc). MATERIALS AND METHODS: Eight newborn
      infants with neonatal hypoglycaemia were studied. The LCMRglc in the whole brain,
      in five cerebral regions and in skeletal muscles were quantitated using positron
      emission tomography (PET) and 2-[18F]Fluoro-2-deoxy-D-glucose (FDG). The PET
      studies were performed at the age of 5.3 +/- 6.2 days during normoglycaemia. The
      LCMRglc of these infants were compared to the age-adjusted LCMRglc of eight
      infants with suspected hypoxic-ischaemic brain injury but with normal
      neurological development. RESULTS: After neonatal hypoglycaemia the age-adjusted
      LCMRglc in the whole brain was not lower than LCMRglc of the control infants
      (5.33 +/- 0.60 mumol/100 g/min vs. 6.71 +/- 0.60 mumol/100 g/min). Also the
      metabolic rate for glucose (MRglc) in the skeletal muscles was similar in
      hypoglycaemic and control infants (5.56 +/- 2.48 mumol/100 g/min vs. 6.99 +/-
      2.41 mumol/100 g/min). CONCLUSION: MRglc in brain and in skeletal muscle seems to
      be normal after neonatal hypoglycaemia, although larger group of patients with
      more severe hypoglycaemia are needed to confirm this finding.

PMID- 9179540
TI  - Parental gender effects on the insulin-gene-associated susceptibility to insulin
      dependent diabetes mellitus.

PMID- 9179541
TI  - Impaired arterial but not venous responsiveness to nitroglycerin in non-insulin
      dependent diabetes mellitus.
AB  - In earlier studies, the response of the arterioles to nitroglycerin (NTG) was
      found to be impaired in non-insulin-dependent diabetes mellitus (NIDDM) patients.
      NTG has major therapeutic effects in reducing cardiac after- and preload. Thus,
      the vasorelaxing efficacy of a therapeutic dose of 0-4 mg of NTG sublingually
      (s.l.) was evaluated in the conduit femoral artery and large veins of
      normotensive, normoalbuminuric NIDDM patients. After NTG, the increase in the
      femoral artery diameter was significantly lower in the NIDDM patients than in
      control subjects: 0.49 (0.29-0.79) vs. 0.75 (0.47-1.00) mm respectively (median,
      interquartile ranges). NTG resulted in an increase of pulse wave transit time in
      the aorta in control subjects but not in the NIDDM patients: from 64 (60-73) to
      70 (63-80) ms, P < 0.02; and from 62 (53-69) to 66 (51-72) ms, P = NS,
      respectively. The reduction in the venous tone of the forearm to NTG was similar
      in both groups. These results suggest that the response to NTG is impaired in the
      arterial system but not in the venous system in well-regulated NIDDM patients
      without diabetic complications.

PMID- 9179542
TI  - Comparison of the effect of two low-density lipoprotein receptor class mutations
      on coronary heart disease among French-Canadian patients heterozygous for
      familial hypercholesterolaemia.
AB  - The aim of this study was to compare the age at first elective coronary angiogram
      and the age at first revascularization (coronary artery bypass grafting or
      percutaneous transluminal coronary angioplasty) in 102 patients without familial
      hypercholesterolaemia (FH), who were matched for age and sex with 76 heterozygous
      FH patients carrying a defective allele at the low-density lipoprotein (LDL)
      receptor gene (LDL-R) and 26 heterozygous FH patients bearing a null mutation at
      the LDL-R. The prevalence of diabetes was significantly higher in the non-FH
      group than in the two FH groups (P < 0.05). Furthermore, mean body mass index
      (BMI) and waist circumference values were also higher in the non-FH group than in
      the two FH heterozygous groups (P < 0.005). However, FH patients who were null
      allele carriers had the highest plasma total and LDL-cholesterol levels and the
      highest cholesterol/HDL-cholesterol ratio, whereas the defective allele carriers
      group had intermediate levels between null allele carriers and non-FH patients.
      Comparison of the age at first coronary angiography revealed that the null allele
      carriers group were younger at first angiogram than the non-FH patients (P <
      0.005). In addition, a trend was observed for a younger age at first angiogram in
      FH heterozygotes bearing a null allele than in carriers of a defective allele (P
      = 0.06). Moreover, null allele carriers were younger at first revascularization
      than defective allele carriers (P < 0.005) or non-FH patients (P < 0.005).
      Finally, the mean number of diseased vessels with > 50% stenosis was higher in
      null allele carriers than in non-FH patients and tended to be higher than among
      defective allele carriers (P < 0.01). Although no difference in plasma Lp(a)
      levels were noted between null allele carrier and non-FH patients, plasma Lp(a)
      concentrations were higher in the defective allele group than in the other two
      groups. In summary, the development of coronary artery disease as estimated by
      the age at first elective coronary angiography or at first revascularization is
      premature in FH patients carrying a null mutation compared with defective allele
      carriers or with non-FH patients. Moreover, the higher number of stenosed vessels
      among null allele carriers suggests that coronary artery disease was more severe
      in FH subjects with a null allele at the LDL-R locus.

PMID- 9179543
TI  - Does hypercalcaemia or calcium antagonism affect human melatonin secretion or
      renal excretion?
AB  - Patients with primary hyperparathyroidism have higher serum melatonin
      concentrations during active disease than after surgical cure. Whether this is
      caused by hypercalcaemia per se, increased parathyroid hormone secretion or other
      mechanisms is unknown. We decided to elucidate whether exogenous hypercalcaemia
      influences melatonin secretion. For this purpose, eight healthy volunteers were
      infused with calcium and saline on separate days and in random order (experiment
      A). Hypercalcaemia inhibited nocturnal melatonin secretion by 20% but left
      urinary melatonin excretion unaffected. If exogenous hypercalcaemia inhibits
      melatonin secretion, it is reasonable to assume that calcium channel blockers
      such as verapamil might have the opposite effect. This was investigated in
      experiment B, in which eight healthy subjects were treated on separate occasions
      with oral verapamil and placebo. Verapamil did not affect nocturnal melatonin
      secretion but increased melatonin excretion by 145%. As 6-sulphatoxy-melatonin is
      the main melatonin metabolite excreted by the kidneys, it was considered
      important to find out whether verapamil would also influence the excretion of 6
      sulphatoxy-melatonin. This was investigated in experiment C, in which eight
      healthy volunteers were treated, on separate occasions, with oral verapamil and
      placebo. In this experiment also, verapamil increased urinary melatonin excretion
      significantly (by 67%), but left excretion of 6-sulphatoxy-melatonin unaffected.
      These findings imply that verapamil influences the renal and/or hepatic handling
      of melatonin.

PMID- 9179544
TI  - Lipoprotein(a), tissue plasminogen activator and plasminogen activator inhibitor
      1 levels in hyperlipidaemic patients in Kuwait.
AB  - Plasma levels of lipoprotein(a) [Lp(a)], tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor type 1 (PAI-1) were assessed in addition to
      anthropometry and levels of glucose, total cholesterol, triglycerides, high
      density lipoprotein (HDL), low-density lipoprotein (LDL) and apo A1 and B in 73
      patients (36 men and 37 women) with primary hyperlipidaemia (group NDHL) in
      Kuwait. Lp(a) levels (212 mg L-1, 8-600 mg L-1, median and range) were similar to
      those obtained in a matched group of 32 non-insulin-dependent diabetes mellitus
      (NIDDM) patients with hyperlipidaemia (218 mg L-1, 50-610 mg L-1) and slightly
      higher, although not significantly so (P = 0.06), than levels seen in 68 healthy
      normolipidaemic control subjects (182 mg L-1, 70-488 mg L-1). tPA levels (8.4 ng
      mL-1, 3.8-18.4 ng mL-1, median and range) in group NDHL were lower than in the
      diabetic group (11.4 ng mL-1, 5.2-14.2 ng mL-1) but higher than in the healthy
      control subjects (7.4 ng mL-1, 2.8-12.6 ng mL-1). PAI-1 levels in group NDHL
      (40.4 ng mL-1, 8.6-55 ng mL-1, median and range) were higher than in the control
      subjects (32.5 ng mL-1, 14.6-46.4 ng mL-1) but lower than in diabetic patients
      (43.8 ng mL-1, 15.6-55 ng mL-1). Hyperlipidaemia phenotype (hypercholesterolaemia
      or hypertriglyceridaemia) did not influence tPA and PAI-1 levels, but Lp(a)
      levels were significantly lower with hypertriglyceridaemia. Gender, cigarette
      smoking and racial origin (Kuwaitis, other Arabs or South Asians) did not affect
      Lp(a), tPA and PAI-1 levels, but tPA levels were higher in postmenopausal
      subjects. Low-density lipoprotein (LDL) levels (whether in total cholesterol or
      as apo B) correlated significantly (P < 0.05) with Lp(a) levels. tPA levels were
      correlated with age and the plasma levels of glucose and uric acid (P < 0.05);
      this correlation with glucose may explain the high levels associated with
      diabetes, whereas the age association might account not only for the differences
      observed between group NDHL and the younger control group but also for the higher
      levels in the postmenopausal women. PAI-1 levels correlated with tPA and
      triglyceride (TG) levels in the groups of subjects (normo- and hyperlipidaemic).
      In the normolipidaemic control group, the significant associations of tPA and PAI
      1 were with body mass, expressed as the body mass index or the waist-hip ratio.
      These results suggest that different factors influence the plasma levels of the
      prothrombotic factors Lp(a), tPA and PAI-1 in healthy control subjects and in
      patients with hyperlipidaemia. In the latter, hyperlipidaemia phenotype, age,
      glycaemic status and uric acid levels are important determinants of the levels of
      these prothrombotic variables, whereas in the healthy, young control population,
      body mass was the single important association with tPA and PAI-1.

PMID- 9179545
TI  - The effect of vitamin C in high doses on plasma and biliary lipid composition in
      patients with cholesterol gallstones: prolongation of the nucleation time.
AB  - Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile
      and formation of cholesterol gallstones. It has been suggested that there may
      also exist an association between vitamin C and cholesterol gallstones in man,
      but such a relationship has not been studied in gallstone patients. In order to
      study the possible effects of vitamin C on gallstone disease in humans, plasma
      lipid levels, hepatic cholesterol metabolism, biliary lipid composition,
      cholesterol saturation and nucleation time of gallbladder bile were analysed in
      16 consecutive gallstone patients, who were planned for laparoscopic
      cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2
      weeks before surgery. The plasma concentration of vitamin C increased by 42% in
      the treatment group. The concentrations of plasma lipids did not differ before
      and after vitamin C treatment; nor did the plasma levels of lathosterol and 7
      alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis
      respectively. The relative concentrations of cholesterol, bile acids and
      cholesterol concentration of bile did not differ significantly between the two
      groups, but the relative concentration of phospholipids was slightly higher in
      the treated group. The bile acid composition was changed; the percentage of
      cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and
      lithocholic acid higher in the vitamin C-treated patients compared with the
      untreated group. The nucleation time was significantly longer in the treatment
      group (7 days) compared with the untreated group (2 days). Our findings indicate
      that vitamin C supplementation may also influence the conditions for cholesterol
      gallstone formation in humans.

PMID- 9179546
TI  - Carbonic anhydrase II in the cerebrospinal fluid: its value as a disease marker.
AB  - Carbonic anhydrase (CA) II is the predominant CA isoenzyme in the brain of
      mammals. We have recently developed a dual-label time-resolved immunofluorometric
      assay to quantify minute amounts of CA I and II in the cerebrospinal fluid (CSF).
      The present study was aimed at elucidating the clinical value of such
      measurements in the case of neurological disorders. Lumbar CSF samples were
      obtained from 111 patients suffering from various neurological diseases and from
      97 control patients with no specific signs of central nervous system diseases.
      The highest CA II concentrations were found in patients with brain infarction
      (median 66.5 micrograms L-1, n = 20), whereas the control patients had markedly
      lower values (median 7.8 micrograms L-1, n = 97). Relative to a reference range
      calculated from the control material (10.2 +/- 17.2 micrograms L-1), the
      sensitivity of CA II measurement in differentiating brain infarction was 100%.
      Patients with transient ischaemic attack (median 11.2 micrograms L-1, n = 9),
      multiple sclerosis (median 14.7 micrograms L-1, n = 18) or epilepsy (median 20.3
      micrograms L-1, n = 17) usually had CA II concentrations within the normal range,
      but those with central nervous system infection (n = 14), dementia (n = 19) or
      trigeminal neuralgia (n = 6) tended to have higher CA II levels in their CSF, the
      median values being 39.1 micrograms L-1, 45.5 micrograms L-1 and 44.0 micrograms
      L-1 respectively. The findings indicate that the concentration of CA II in the
      CSF marks disease activity in patients with brain damage. This finding could
      provide a basis for further studies estimating the value of CA II measurement as
      a new laboratory marker of diseases affecting the brain.

PMID- 9179547
TI  - Neutrophil superoxide release and interleukin 8 in acute myocardial infarction:
      distinction between complicated and uncomplicated states.
AB  - Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were
      determined in 15 patients with complicated acute myocardial infarction (MI) and
      15 patients with uncomplicated MI. All patients showed increased superoxide
      release in unstimulated and stimulated neutrophils compared with healthy control
      subjects, indicating priming of these cells. Superoxide release of unstimulated
      or stimulated neutrophils was found to be significantly higher in patients with
      complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did
      not affect the rates of superoxide release. The neutrophil
      chemoattractant/activator IL-8 was detected in the sera of all patients, with
      significantly higher levels in those with complicated MI. The highest levels of
      IL-8 were detected at admission to the Coronary Care Unit and significantly
      decreased thereafter, suggesting its contribution to neutrophil-mediated tissue
      injury. The high levels of IL-8 may be one of the major contributors to the
      priming of neutrophils in these patients.

PMID- 9179548
TI  - Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not
      modify the fatty acid composition of serum lipids in obese subjects.
AB  - Intestinal fatty acid binding protein (I-FABP) participates in the metabolism of
      fatty acids in the intestinal enterocytes. Threonine encoding allele in codon 54
      of the I-FABP gene has been suggested as regulating the absorption of long-chain
      fatty acids. We examined the fatty acid composition of serum lipid fractions and
      the concentration of serum free fatty acids after an overnight fast in obese
      subjects, aged 24-56 years, on their habitual diet. The body mass index of the
      subjects ranged from 29.7 to 43.3 kg m-2. Six subjects were homozygous for the
      Thr-54 allele of the I-FABP gene, 37 subjects were heterozygous for the Thr
      54/Ala-54 allele and 24 subjects were homozygous for the Ala-54 allele. We did
      not find any consistent differences in the proportions of long-chain fatty acids
      in serum triglycerides, cholesterol esters or phospholipids, but the
      concentration of serum free fatty acids tended to be higher in subjects who were
      homozygous for the Thr-54 allele (P = 0.13, for trend). In conclusion, our
      findings suggest that a polymorphism at codon 54 of the I-FABP2 gene does not
      substantially modify the fatty acid composition of serum lipids in obese Finns.

PMID- 9179549
TI  - Small bowel bacterial overgrowth in patients after total gastrectomy.
AB  - The aim of this study was to elucidate the consequences of small bowel bacterial
      overgrowth (SBBO) after total gastrectomy. A total of 127 patients, evaluated for
      SBBO with a radiographically controlled H2-breath test (subgroup I, without SBBO,
      n = 80; subgroup II, with SBBO, n = 47) after potentially curative total
      gastrectomy for gastric malignancy, were uniformly evaluated. Mean time since
      operation was significantly shorter in subgroup II than in subgroup I [370 days,
      confidence interval (CI) 96-645 days, vs. 687 days, CI 397-976 days; P < 0.01].
      Controlling for this difference, there were no other significant differences in
      symptoms and signs between the subgroups except for the medico-social functioning
      measured with the Edinburgh Rehabilitation Status Scale (ERSS). The mean ERSS
      showed significantly better medicosocial functioning in subgroup I than in
      subgroup II [3.7 (CI 2.2-5.2) vs. 5.1 (CI 3.0-7.0); P < 0.05]. After total
      gastrectomy, patients without SBBO did not differ significantly from patients
      with SBBO in most parameters. Medicosocial functioning was significantly poorer
      in the latter.

PMID- 9179550
TI  - Response of myocardial cellular energy metabolism to variation of buffer
      composition during open-chest experimental cardiopulmonary resuscitation in the
      pig.
AB  - The aim of the present study was to investigate possible relationships in piglets
      between myocardial energy-related metabolites and intracellular electrolytes
      during open-chest cardiopulmonary resuscitation (OCCPR) supplemented by the
      administration of alkaline buffers with varying sodium content. Our hypothesis
      was that an increasing myocardial intracellular sodium content would decrease the
      intracellular energy stores. In addition to haemodynamics, acid-base and blood
      gas variables were analysed, and myocardial biopsies were collected before and
      during OCCPR as well as after the return of spontaneous circulation. After a
      period of 4 min of untreated ventricular fibrillation (VF). 25 piglets were
      randomly allocated to one of four groups: OCCPR with normal saline (n = 5); OCCPR
      with sodium bicarbonate (SB) (n = 7); OCCPR with Tris buffer mixture (TBM) (n =
      7); and a totally untreated control group (n = 6). The results showed that 4 min
      of untreated VF almost eradicated creatine phosphate (CrP) and that the ATP/ADP
      ratio decreased to 1.5-2.0. During OCCPR with normal saline, the myocardial
      content of CrP increased, whereas lactate, ATP and ADP levelled off and AMP
      decreased, causing an increased ATP/ADP ratio. The adenosine and inosine contents
      increased, whereas inosine monophosphate was unchanged at a low level, the
      adenosine and inosine contents being inversely correlated with the total content
      of adenine nucleotides. In both buffered groups, the increase in most energy
      related metabolites (CrP, ATP, ADP, AMP and the ATP/ADP quotient) was less and in
      lactate more pronounced than in the group not being buffered, with no difference
      between the groups receiving SB or TBM. Although the intracellular potassium
      content was unaltered, the sodium, chloride and calcium concentration increased,
      more so in the group receiving SB. The intracellular content of sodium was
      correlated with that of calcium. Thus, buffering increased the myocardial AMP
      degradation during OCCPR by increasing the flux via the 5'-nucleotidase reaction,
      and SB increased the intracellular contents of sodium and calcium to a greater
      extent than did TBM.

PMID- 9179551
TI  - Long-term use of smokeless tobacco and physical performance in middle-aged men.
AB  - To determine the influence of prolonged nicotine exposure on maximal physical
      working capacity, a study of clinical measures of physical fitness and
      cardiovascular response to exercise was performed in 144 healthy men, 35-60 years
      old, subdivided into smokeless tobacco users, smokers and non-users of tobacco.
      Regular users of smokeless tobacco, with exposures of more than 20 years, showed
      similar maximal oxygen uptake (mean 3.48 L min-1, SD 0.49, n = 48) to non-users
      (mean 3.51 L min-1, SD 0.51, n = 65). In smokeless tobacco users, higher blood
      pressure and heart rate values were observed at rest and at submaximal work,
      after exposure to tobacco shortly before the exercise test, but not at maximal
      work. However, significantly lower maximal oxygen uptake was found for smokers
      (mean 2.88 L min-1, SD 0.49, n = 31) compared with non-users (P < 0.001). Plasma
      concentration of continine, the main metabolite of nicotine, was significantly
      higher in smokeless tobacco users (mean 347 ng mL-1, SD 175, n = 48) than in
      smokers (mean 253 ng mL-1, SD 153, n = 31, P < 0.001). The findings indicate that
      long-term use of smokeless tobacco does not significantly influence exercise
      capacity in healthy, physically well-trained subjects.

PMID- 9179552
TI  - The 13C-mixed triglyceride breath test in healthy adults: determinants of the
      13CO2 response.
AB  - Defects in lipolysis due to pancreatic insufficiency can be diagnosed by the
      mixed triglyceride (MTG) 13CO2 breath test. However, the effects of various test
      conditions on the 13CO2 response have only been partially elucidated. In healthy
      adults, we performed the 13CO2 mixed triglyceride breath test and we compared (a)
      the inter- and intra-individual variation in the 13CO2 response; (b) the effect
      of two different test meals; (c) the effect of an additional meal during the
      test; and (d) the effect of physical exercise during the test. Upon repeating the
      test in the same individual (test meal cream), repeatability coefficients were
      large, with respect to either time to maximum 13C excretion rate (3.8 h). maximum
      13C excretion rate (4.9% 13C dose h-1) or cumulative recovery of 13C over the 9-h
      study period (22.7% 13C dose). The cumulative 13C expiration over 9 h obtained
      with the test meal composed of cream was quantitatively similar to that obtained
      with bread and butter: 42.2 +/- 8.4% and 47.7 +/- 6.3% respectively. Fasting for
      9 h during the test resulted in similar 13C expiration rates and cumulative 13C
      expiration (43.4% +/- 7.2%) when compared with consumption of an additional meal
      3 h after the start of the test (38.3 +/- 5.3%). The 13CO2 response increased in
      five out of seven subjects, but decreased in the other two, when moderate
      exercise was performed (bicycle ergometer, 50 W for 5 h). We conclude that the
      repeatability of the MTG test in healthy adults is low. The present results
      indicate that a solid and a liquid test meal, containing a similar amount of
      fats, give similar cumulative 13CO2 responses, and that stringent prolonged
      fasting during the test is unnecessary. Standardization of physical activity
      seems preferable, since the unequivocal effects of moderate exercise on the 13CO2
      response were observed in the individuals studied.

PMID- 9179553
TI  - Effects of aerobic exercise training and yoga on the baroreflex in healthy
      elderly persons.
AB  - It is unclear whether the age-associated reduction in baroreflex sensitivity is
      modifiable by exercise training. The effects of aerobic exercise training and
      yoga, a non-aerobic control intervention, on the baroreflex of elderly persons
      was determined. Baroreflex sensitivity was quantified by the alpha-index, at high
      frequency (HF; 0.15-0.35 Hz, reflecting parasympathetic activity) and mid
      frequency (MF; 0.05-0.15 Hz, reflecting sympathetic activity as well), derived
      from spectral and cross-spectral analysis of spontaneous fluctuations in heart
      rate and blood pressure. Twenty-six (10 women) sedentary, healthy, normotensive
      elderly (mean 68 years, range 62-81 years) subjects were studied. Fourteen (4
      women) of the sedentary elderly subjects completed 6 weeks of aerobic training,
      while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate
      decreased following yoga (69 +/- 8 vs. 61 +/- 7 min-1, P < 0.05) but not aerobic
      training (66 +/- 8 vs. 63 +/- 9 min-1, P = 0.29). VO2 max increased by 11%
      following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No
      significant change in alpha MF (6.5 +/- 3.5 vs. 6.2 +/- 3.0 ms mmHg-1, P = 0.69)
      or alpha HF (8.5 +/- 4.7 vs. 8.9 +/- 3.5 ms mmHg-1, P = 0.65) occurred after
      aerobic training. Following yoga, alpha HF (8.0 +/- 3.6 vs. 11.5 +/- 5.2 ms mmHg
      1, P < 0.01) but not alpha MF (6.5 +/- 3.0 vs. 7.6 +/- 2.8 ms mmHg-1, P = 0.29)
      increased. Short-duration aerobic training does not modify the alpha-index at
      alpha MF or alpha HF in healthy normotensive elderly subjects. alpha HF but not
      alpha MF increased following yoga, suggesting that these parameters are measuring
      distinct aspects of the baroreflex that are separately modifiable.

PMID- 9179554
TI  - Smoking cessation improves insulin sensitivity in healthy middle-aged men.
AB  - Cigarette smokers have recently been shown to exhibit insulin resistance,
      dyslipidaemia and markers of the insulin resistance syndrome (IRS). The aim of
      this study was to examine the effects of smoking cessation on insulin sensitivity
      and IRS. Forty male, non-obese healthy smokers participated in this open parallel
      study with 8 weeks of follow-up. Seventeen subjects were able to stop smoking,
      while 23 subjects continued to smoke and served as a controls group.
      Anthropometric and metabolic data were measured. Degree of insulin sensitivity
      was determined with the euglycaemic hyperinsulinaemic clamp technique. Smoking
      cessation increased insulin sensitivity and improved the lipoprotein profile in
      spite of a modest increase in body weight. Initial smoking habits correlated
      positively with the increase in BMI as well as the improvements in the metabolic
      variables after smoking cessation. These data support the view that smoking
      causes insulin resistance and IRS, and also demonstrate that the beneficial
      metabolic effects of smoking cessation override the effects of an accompanying
      modest increase in body weight.

PMID- 9179555
TI  - Practical uses of individual pharmacokinetic parameters in drug development and
      clinical practice: examples and simulations.
AB  - This article summarizes the practical uses of the six key pharmacokinetic
      parameters, i.e. elimination half-life, volume of distribution, total clearance,
      fraction of administered dose eliminated by the kidneys, free fraction in plasma,
      and bioavailability. Emphasis is on the practical medical uses of these
      parameters in clinical practice and drug development. Numerous pharmacokinetic
      simulations are used to illustrate the different practical uses. The principles
      underlying drug dosage regimen design, drug concentration monitoring and
      adjustment, and dosage adjustment in renal disease are also discussed.

PMID- 9179556
TI  - Influence of partial hepatectomy in rats on the activity of hepatic microsomal
      enzymatic systems.
AB  - The influence of partial hepatectomy on the activity of the hepatic microsomal
      enzymatic systems was determined in rats. Cytochrome P-450, cytochrome b5, four
      mixed functional oxidase (MFO) activities (microsomal aniline hydroxylase, p
      nitroanisole O-demethylase, aminopyrine N-demethylase and NADPH cytochrome c
      reductase) and glutathione levels were measured in unhepatectomized rats (control
      group) and in hepatectomized rats 12 h, 24 h, 3 days and 6 days after 70%
      hepatectomy. Following surgery the remaining lobes of the liver grow rapidly in
      order to restore the original liver mass. Partial hepatectomy significantly
      reduces cytochrome P-450 and b5 content in the remaining liver as well as the
      four MFO activities studied. But when the enzymatic systems are expressed as
      nmoles/mg microsomal protein, only cytochrome P-450 shows statistical
      differences. The hepatic biotransformation capacity of drugs and xenobiotics
      decreases during the regeneration period due to the reduction of hepatic mass
      rather than because of a reduction of their metabolic capacity. Glutathione
      levels are increased after partial hepatectomy but increased glutathione
      dependent protector mechanisms are not expected.

PMID- 9179557
TI  - Metabolism of 4-[1-(2-fluoro-4-biphenylyl)ethyl]-2-methylaminothiazole (SM-8849)
      in rats.
AB  - Metabolism of 4-[1-(2-fluoro-4-biphenylyl)ethyl]-2-methylaminothiazole (SM-8849),
      a novel immunomodulatory agent, in rats was investigated. By co-chromatography
      with authentic samples, desmethylated (SM-8800) p-hydroxylated (SL-5512) and
      desmethylated-p-hydroxylated SM-8849 (SL-5515) were detected in the bile.
      Thermospray mass spectrometry (TSP-MS) analysis of five metabolites isolated from
      the bile revealed molecular ions of both conjugates (glucuronides and a sulfate)
      and their aglycones. Aglycone structures were determined by comparison of their
      product spectra with those of authentic standards. Further analyses of
      conjugation sites were carried out by 1H-NMR including differential NOE. As a
      result, the sulfate of SL-5515 (5515-S), the N-glucuronides of SL-5512 and SM
      8849 (5512-NG and 8849-NG, respectively), the glucuronide of SL-5512 (5512-G) and
      the O-glucuronide of 4-hydroxy-3-methoxy-SM-8849 (CatOMe-OG) were identified. In
      addition, N-methylthiouras was identified in urine by LC/MS/MS.

PMID- 9179558
TI  - Ciprofloxacin decreases plasma phenytoin concentrations in the rat.
AB  - The pharmacokinetic interaction between phenytoin and ciprofloxacin was studied
      in rats. One group of animals was given phenytoin (20 mg/kg, p.o.) as a single
      daily dose for 7 days. In another group of animals, the same protocol was
      followed except that ciprofloxacin was given in two equal doses (15 mg/kg, i.p.,
      each) on days 5, 6 and 7. On day 8, phenytoin blood sampling was performed at
      0.083, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h. Similarly, urine
      samples were collected at 4, 6 and 8 h following drug administration from the
      same animals that had received either phenytoin alone or phenytoin together with
      ciprofloxacin. The concentrations of phenytoin in the plasma and urine were
      measured using an HPLC method. Ciprofloxacin significantly (P < 0.05) reduced the
      area under the curve (AUC), the maximum plasma concentration (Cmax) and the
      elimination half-life (t1/2) of phenytoin. Additionally, ciprofloxacin increased
      phenytoin concentrations in urine at 4, 6 and 8 h. These results show that
      ciprofloxacin decreases the plasma levels of phenytoin when the two drugs are
      given concurrently.

PMID- 9179559
TI  - An approach for determination of chronopharmacokinetic parameters of
      methotrexate.
AB  - In classical pharmacokinetic studies, the organism is represented by one or
      several compartments described by a system of linear differential equations with
      constant coefficients. A system of linear differential equations can not describe
      the compartmental model in the presence of chronobiological variations. The
      purpose of this study is to calculate the chronopharmacokinetic parameters of
      Methotrexate, which presents this type of variation.

PMID- 9179560
TI  - Pharmacokinetics of a new oral formulation of amoxicillin.
AB  - The bioavailability of the recently developed 1 g dispersible tablet form of
      amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were
      compared to that of the 1 g standard reference formulation (A). Twelve healthy
      volunteers were involved in this single-dose, open, randomized, three-way cross
      over study. The mean peak serum levels were 14.1 +/- 4.1 micrograms/ml after A,
      15.1 +/- 3.1 micrograms/ml after B and 15.1 +/- 5.4 micrograms/ml after C. The
      area under the drug concentration versus time curves were 47.6 +/- 12.0
      micrograms.h/ml after A, 52.8 +/- 10.2 micrograms.h/ml after B and 51.1 +/- 13.8
      micrograms.h/ml after C. On the basis of these two pharmacokinetic parameters,
      the three formulations were found to be bioequivalent. In addition, the predicted
      serum concentrations during multiple dosing (3 times a day), derived from the
      corresponding mean concentrations after a single 1 g dose of C showed that 8
      hourly administration would yield therapeutic serum concentrations for infections
      such as uncomplicated community-acquired pneumonia due to susceptible or less
      susceptible strains in otherwise healthy subjects.

PMID- 9179561
TI  - Disposition of DX-52-1, a novel anticancer agent, after intravenous
      administration to mice and dogs.
AB  - DX-52-1 is a new derivative of a quinocarmycin analogue. The disposition of [3H]
      DX-52-1 was investigated in mice and dogs after intravenous administration (4 and
      0.15 mg/kg, respectively). The plasma concentration of non-volatile radioactivity
      was 7.4 micrograms eq./ml 3 min after administration to mice, then declined
      biphasically until 2 h. The distribution of non-volatile radioactivity into blood
      cells was 20% 3 min after administration, being maintained until 30 min. The
      plasma concentration of unchanged drug was almost equal to that of the
      radioactivity 3 min after administration and the unchanged drug ratio decreased
      rapidly. High radioactivity was found in the gall bladder, kidney, liver, and
      lung 15 min after administration. No radioactivity was detected in most tissues
      24 h post-administration. The cumulative excretion of total radioactivity into
      urine and feces after administration was 68 and 28% within 96 h, respectively.
      The plasma concentration of non-volatile radioactivity was 0.65 micrograms eq./ml
      3 min after administration to dogs. The distribution of non-volatile
      radioactivity into blood cells was about 20% 3 min after administration and this
      level tended to increase with time. The cumulative excretion of total
      radioactivity into urine and feces after administration was 62 and 24%,
      respectively.

PMID- 9179562
TI  - Metabolism of mangafodipir trisodium (MnDPDP), a new contrast medium for magnetic
      resonance imaging, in beagle dogs.
AB  - The metabolism of MnDPDP (manganese(II) N,N'-dipyridoxylethylenediamine-N,N'
      diacetate-5,5'-bis(phosphate) was studied in dogs after intravenous infusion for
      12.5 min with either 10, 30 or 100 mumol MnDPDP/kg b.w. HPLC analyses of plasma
      samples obtained 1, 5 and 30 min after the end of infusion revealed that MnDPDP
      was rapidly dephosphorylated to MnDPMP (manganese(II) N,N'
      dipyridoxylethylenediamine-N,N'-diacetate-5-phosphate) and MnPLED (manganese(II)
      N,N'-dipyridoxylethylenediamine-N,N'-diacetate), with simultaneous
      transmetallation to the corresponding zinc metabolites ZnDPDP, ZnDPMP and ZnPLED.
      In the low-dose group, the parent compound MnDPDP was present at the lowest
      concentration compared to the metabolites at the first sampling time point, 1 min
      after the end of infusion, whereas MnPLED was the main metabolic. At 30 min post
      infusion ZnPLED was the main metabolite. The medium- and high-dose groups showed
      a similar metabolic pattern. In the high-dose group, MnPLED was the main
      metabolite at all sampling time points. The estimated plasma half-life of total
      ligand was 20 min, and it was dose-independent with an apparent volume of
      distribution of 0.2 l/kg. The rate of dephosphorylation was similar to the rate
      of transmetallation, and both were dose-independent. However, calculations of the
      total Mn and Zn ligands indicated that the apparent plasma elimination was dose
      dependent. The half-life for total Mn ligands which is a combination of both
      metabolism and elimination, were 10 and 20 min at 10 and 100 mumol/kg,
      respectively. The half-life for total Zn ligands which is the half-life for rate
      of formation of Zn ligands, were 40 and 65 min at 10 and 100 mumol/kg,
      respectively. No sex differences in metabolic pattern were observed in any of the
      three dosage groups.

PMID- 9179563
TI  - Distribution study of radioactivity in rats after oral administration of the
      lipido/sterolic extract of Serenoa repens (Permixon) supplemented with [1-14C]
      lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol.
AB  - The study carried out on rats given orally the n-hexane lipido/sterolic extract
      of Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids
      or beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues
      shows the highest level in the case of administration of LSESR supplemented with
      [14C]-labelled oleic acid. This was clearly demonstrated on a rat with an induced
      fibro-muscular hyperplasia of the prostate and by quantitative measurements of
      radioactivity. Ratios of radioactivity in tissues compared to plasma show an
      uptake of radioactivity greater in prostate as compared to other genital organs,
      i.e. the seminal vesicles or to other organs such as liver.

PMID- 9179564
TI  - Cruciferous vegetables and drug metabolism.

PMID- 9179565
TI  - Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and
      hyperglycaemia.
AB  - 1. Vasodilatation induced by adenosine is mediated through the activation of A2
      purinoceptors in endothelial and smooth muscle cells. 2. Adenosine induces a
      rapid and transient membrane hyperpolarization in endothelial cells. 3. Acute
      exposure to adenosine or A2-purinoceptor agonists activates the L-arginine-NO
      signalling pathway in human endothelial cells in vitro.

PMID- 9179566
TI  - Calibration of Mg(2+)-selective macroelectrodes down to 1 mumol l-1 in
      intracellular and Ca(2+)-containing extracellular solutions.
AB  - Using Mg(2+)-selective macroelectrodes based on the neutral carriers ETH 7025 and
      ETH 5506, methods were developed to determine accurately the apparent binding
      constant (Kapp) and purity, and hence the ionized magnesium concentration
      ([Mg2+]), in Ca(2+)-free, Mg2+ buffer solutions manufactured with either CDTA
      (trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid monohydrate) or EDTA. In
      nominally Ca(2+)-free solutions, calibration of the macroelectrodes was possible
      down to 1 mumol l-1 in both intracellular (ETH 7025)- and extracellular (ETH
      5506)-like physiological solutions. The measured [Mg2+] in the buffer solutions
      overlapped with the [Mg2+] set by dilution alone, suggesting that the method was
      reliable. These buffer solutions could then be used to manufacture standard Mg2+
      solution containing known [Mg2+] at a set calcium concentration. Ca2+ sensitivity
      limits the use of ETH 7025 and, for extracellular measurements in Ca(2+)
      containing solutions, Mg(2+)-selective macroelectrodes manufactured with ETH 5506
      were the electrodes of choice. In 0.5-0.9 mmol l-1 Ca+, measurement of [Mg2+] was
      possible down to 10 mumol l-1. At [Mg2+] greater than 0.25 mmol l-1 there was no
      interference from Ca2+ (0.5-1.5 mmol l-1). With CDTA and/or EDTA buffer solutions
      there was a wide variation between the calculated values for the [Mg2+] and the
      measured [Mg2+] (the calculated values differed by a factor of up to 4.5 and 3,
      respectively). At present, measurement of the Kapp and ligand purity in the
      appropriate solution at the desired pH and temperature would seem to be the best
      strategy to adopt rather than attempting to calculate the constant. Since no
      recognized international standard exists for [Mg2+] at the micromolar level,
      values in the literature for Kd, etc. in this range can only be regarded as
      approximate.

PMID- 9179567
TI  - The effect of cromakalim on intracellular [Ca2+] in isolated rat skeletal muscle
      during fatigue and metabolic blockade.
AB  - The effects of the ATP-sensitive K+ channel (KATP channel) opener cromakalim on
      excitation-contraction (E-C) coupling were studied in skeletal muscle during
      fatiguing and non-fatiguing activity. Intracellular calcium concentration
      ([Ca2+]i) was monitored using the fluorescent indicator fura-2 in isolated single
      skeletal muscle fibres enzymatically dissociated from rat flexor digitorum
      brevis. A protocol of tetanic stimulation (50 Hz for 300 ms) with progressively
      shorter durations between tetani was used to induce E-C coupling failure in these
      cells. Cromakalim (100-800 microM) had little effect on peak [Ca2+]i during
      twitch and non-fatiguing tetanic stimulation. However, with 0.4 s between tetani,
      100 microM cromakalim decreased peak tetanic [Ca2+]i from 1.47 +/- 0.11 microM to
      8.35 +/- 55 nM, but did not affect resting [Ca2+]i (control, 220 +/- 40 nM; with
      cromakalim, 171 +/- 33 nM). Cyanide (2 mM) decreased tetanic [Ca2+]i and
      increased resting [Ca2+]i during the stimulus protocol; with 0.4 s between
      tetani, peak [Ca2+]i was 820 +/- 50 nM and resting [Ca2+]i was 443 +/- 32 nM. The
      ability of cromakalim to inhibit E-C coupling was enhanced by the presence of
      cyanide. Complete blockade of metabolism by cyanide and iodoactetate (0.1 mM)
      caused a marked rise in resting [Ca2+]i and inhibition of the tetanic rise of
      [Ca2+]i. With cromakalim (100 microM) present, E-C coupling failed during
      metabolic blockade but without a significant increase in resting [Ca2+]i. These
      results are consistent with a role for the KATP channel in the failure of Ca2+
      release during fatigue.

PMID- 9179568
TI  - Responses of neurones in the medullary raphe nuclei to inputs from visceral
      nociceptors and the ventrolateral periaqueductal grey in the rat.
AB  - The ventrolateral periaqueductal grey matter (PAG) is believed to have a role in
      mediating cardiovascular responses to noxious visceral stimuli. The present study
      was carried out as a first stage in establishing whether the ventrolateral PAG
      may exert these influences after a relay in the caudal medullary raphe nuclei
      (nucleus raphe obscurus and nucleus raphe pallidus). Single unit extracellular
      recordings were made from neurones in the caudal raphe nuclei and, for
      comparison, in the more rostral nucleus raphe magnus in Saffan-anaesthetized and
      paralysed rats. Neurones in the mid-line medulla were tested for their responses
      to electrical stimulation at chemically identified depressor sites in the
      ventrolateral PAG and to noxious visceral stimuli (distensions of the urinary
      bladder and electrical stimulation of the greater splanchnic nerve). Fifty-two
      per cent of caudal and 74% of rostral mid-line neurones gave short latency
      excitatory responses to stimulation of depressor sites in the ventrolateral PAG.
      Of the neurones that were also tested with noxious visceral stimuli, 5% of the
      caudal and 47% of the rostral neurones responded to bladder distension, while 33
      and 35%, respectively, of caudal and rostral neurones responded to splanchnic
      nerve stimulation. These results indicate that many mid-line medullary neurones
      receive inputs from both the ventrolateral PAG and visceral nociceptors and may,
      therefore, be part of the output pathway by which the ventrolateral PAG produces
      integrated physiological responses to noxious visceral stimuli.

PMID- 9179569
TI  - Direct vascular effects of plantain extract in rats.
AB  - Responses of the aorta and portal veins isolated from rats to aqueous extract of
      plantain (Musa paradisiaca) were studied. The extract produced concentration
      dependent relaxation in both noradrenaline- and KCl-contracted aortic rings. The
      maximum relaxation in noradrenaline-contracted rings was 52.49 +/- 6.63% and in
      KCl-contracted rings was 77.51 +/- 2.52% of the initial tensions developed in
      response to the contractile agents. The extract also produced significant (P <
      0.01) inhibition of the maximum aortic contractile response to noradrenaline and
      completely abolished the spontaneous contractions of the portal veins. Serotonin
      (5-hydroxytryptamine), unlike the extract, produced contraction rather than
      relaxation of the aortic rings. The results show a non-specific relaxing and
      inhibiting effect of plantain extract on aortic and portal smooth muscles, an
      effect that is not attributable to its abundant serotonin content.

PMID- 9179570
TI  - Effect of adrenaline and alpha-agonists on net rate of liquid absorption from the
      pleural space of rabbits.
AB  - Indirect evidence supporting a solute-coupled liquid absorption from the pleural
      space of rabbits has recently been provided; moreover, the beta 2-adrenoceptor
      agonist terbutaline has been found to increase this absorption. In this study the
      effect of adrenaline and alpha-adrenoceptor agonists on net rate of liquid
      absorption (Jnet) from albumin Ringer hydrothoraces of various sizes has been
      determined in anaesthetized rabbits. In hydrothoraces with adrenaline (5 x 10(-6)
      M) the relationship between Jnet and volume of liquid injected was displaced
      upwards by 0.09 ml h-1 relative to that in control hydrothoraces (P < 0.01). This
      displacement did not occur with lower adrenaline concentrations or after
      pretreatment with the beta-blocker propranolol. Hence, this increase in Jnet is
      mediated by stimulation of beta-receptors. It seems to be caused by an increase
      in solute-coupled liquid absorption, since beta-agonists inhibit lymphatic
      activity while, at relatively high concentrations, they may increase active
      transport. Conversely, the strong stimulation of lymphatic alpha-receptors that
      should occur with adrenaline after beta-blockade may fail to increase lymphatic
      drainage, because it has been shown that the increase in contraction frequency of
      lymphatics may be balanced by the decrease in their stroke volume. Arterial blood
      pressure during the hydrothoraces with adrenaline was unchanged. In hydrothoraces
      with the alpha 2-agonist clonidine (5 x 10(-6) M; a less potent agent than
      adrenaline) the slope of the relationship between Jnet and volume injected
      increased by 26% (P < 0.01), while its origin did not change. This increase in
      slope did not occur with a lower clonidine concentration or after pretreatment
      with the alpha-blocker phentolamine. Hence, it is caused by stimulation of alpha
      2-receptors, which probably lead to an increase in lymphatic drainage related to
      liquid load. In hydrothoraces with the alpha 1-agonist phenylephrine (5 x 10(-6)
      or 10(-7) M) Jnet was simlar to control values.

PMID- 9179571
TI  - Beta-agonist-induced activation of Na+ absorption and KCl release in rat fetal
      distal lung epithelium: a study of cell volume regulation.
AB  - The effects of terbutaline (a selective beta 2-adrenoceptor agonist) on cell
      volume and ion transport in rat fetal distal lung epithelial (FDLE) cells were
      studied. In FDLE cells, benzamil (1 microM) induced cell shrinkage, while cell
      volume was increased by 1 mM quinine or 2 mM Ba2+ but was not affected by 5-nitro
      2-(3-phenylpropylamino)-benzoic acid (NPPB, 20 microM). Terbutaline (10 nM)
      induced transient cell swelling, which was suppressed by benzamil, while 10
      microM terbutaline induced initial rapid cell shrinkage followed by delayed slow
      cell shrinkage, which was suppressed by 1 mM quinine or 20 microM NPPB but not by
      2 mM Ba2+. Application of benzamil enhanced the cell shrinkage induced by 10
      microM terbutaline. These observations suggest that: (1) benzamil-blockable Na(+)
      permeable channels and quinine- and Ba(2+)-blockable K+ channels contribute to
      maintenance of cell volume of FDLE cells; (2) terbutaline at both 10 nM and 10
      microM activates benzamil-blockable Na(+)-permeable channels; (3) quinine
      blockable K+ channels are activated by 10 microM terbutaline; and (4) NPPB
      blockable Cl- channels are responsible for Cl- movement in cell volume changes
      induced by terbutaline. The present study demonstrates that the cellular
      mechanisms of volume change induced by terbutaline are closely related to
      activation of Na+ absorption and KCl release.

PMID- 9179572
TI  - The effect of passive stretch on the response of the fetal rabbit ductus
      arteriosus to indomethacin, noradrenaline and prostaglandin E2.
AB  - The aim of this study was to determine the effect of varying stretch of the
      ductus arteriosus on its contractile response to indomethacin and noradrenaline,
      and its relaxant response to prostaglandin (PG) E2. Isolated rings of ductus
      arteriosus obtained from fetal New Zealand White rabbits at 28 days gestation
      were mounted in vitro for measurement of isometric tension by a transducer
      connected to a vernier control. The responses of the ductus to drugs at varying
      degrees of passive stretch were corrected to a standard contraction in response
      to 65 mM potassium at a standard level of stretch. Increasing stretch across the
      range 1.0-5.9 mN increased the contractile response to indomethacin and
      noradrenaline (the latter in the presence of 1 microM indomethacin and 1 or 10 nM
      PGE2) in a virtually identical manner. The sensitivity of the vessel to
      noradrenaline in the presence and absence of indomethacin and its sensitivity to
      the relaxant effect of PGE2 in the presence of indomethacin were unaffected by
      increasing stretch. The extent of contractile tone present which was not
      inhibited by endogenous PGE2 increased with increasing stretch. It was concluded
      that: (1) the contractile response to indomethacin can be profoundly altered by
      the degree of spontaneous tone in the vessel; (2) the magnitude of the
      contraction induced by indomethacin is not a good index of the degree of
      inhibition exerted by locally produced PGs in the vessel; and (3) locally
      produced PGs are likely to have a physiological role in maintaining patency of
      the ductus arteriosus in utero.

PMID- 9179573
TI  - Integrative role of medullary neurons of the cat during exercise.
AB  - The co-ordinated cardiovascular and respiratory responses observed during
      exercise are mediated by both afferent activation arising in contracting skeletal
      muscles and descending central drive originating in brain regions rostral to the
      medulla. Even though integration of these two mechanisms must occur in order to
      produce alterations in cardiorespiratory activity proportional to the intensity
      of the exercise, little is known about how this integration occurs. The purpose
      of the present study was to examine the role of medullary sites in the
      integration of exercise drives to the cardiovascular and respiratory systems. The
      responses of neurons in the ventrolateral medulla and the lateral tegmental
      fields to contraction of hindlimb muscles (elicited by stimulation of the L7 S1
      ventral roots) and to activation of simulated central command (caudal
      hypothalamic stimulation) were examined in anaesthetized cats. Muscular
      contraction evoked an increase in discharge frequency in 59% (24/41) of the
      medullary neurons; 58% (14/24) of these neurons excited by muscular contraction
      displayed an immediate increase and 42% (10/24) had a more delayed increase in
      discharge frequency. Eighty-three per cent (10/12) of neurons rapidly excited by
      hindlimb muscle contraction were inhibited by hypothalamic stimulation. In
      contrast, most neurons which showed a delayed increase in discharge frequency
      during muscle contraction were either excited by hypothalamic stimulation (5/10)
      or unaffected (4/10). The majority of medullary neurons studied possessed a basal
      discharge related to the cardiovascular, respiratory and/or sympathetic cycles.
      These findings demonstrate that both feedback from contracting muscles and
      descending central command impinge upon individual medullary neurons. This is
      consistent with the idea that medullary neurons are important in integrating both
      the central drive and peripheral reflexes controlling the cardiorespiratory
      responses to exercise.

PMID- 9179574
TI  - Synchronization of human finger movements: delays and sex differences with
      isotonic 'antiphase' motion.
AB  - The interval between the operation of two Morse keys, or the moments at which
      fingers touched or broke contact with electrical conductors, has been measured,
      the subjects making the movements as synchronously as possible. The data obtained
      deal with timings when two fingers flexed or extended together ('in phase') and
      when one finger extended whilst the other flexed ('antiphase'). For antiphase
      movements of the index fingers with the conductors, flexion usually occurred
      before extension so there was 'overlap'. Statistically, this period was greater
      in women and unusually high values were found in one subject with mild cerebral
      palsy. Overlap was not found using the keys. Using conductors, the timing of
      antiphase movements for the index and middle fingers of the right and left hand
      showed overlap again. No significant relationships were found with handedness.
      When the conductors were placed above the fingers, and the contact was thus with
      the dorsum, extension took place before flexion: both fingers were extended for a
      while, with overlap occurring again. The significance of these findings for the
      understanding of motor control is discussed.

PMID- 9179575
TI  - Task-dependent effect of limb immobilization on the fatigability of the elbow
      flexor muscles in humans.
AB  - Because short-term limb immobilization produces selective adaptations in the
      neuromuscular system that probably interact with the task-dependent expression of
      muscle fatigue, the purpose of this study was to determine the effects of limb
      immobilization on the ability of human subjects to sustain isometric contractions
      at low and moderate submaximal forces. Four weeks of elbow joint immobilization
      caused a substantial decrease in the daily activity of biceps brachii during
      immobilization, a significant reduction in the cross-sectional area and volume of
      the elbow flexor muscles as measured by magnetic resonance imaging, and a decline
      in the maximum voluntary contraction (MVC) activation and force of the elbow
      flexor muscles. Immobilization had a task-dependent effect on muscle fatigue with
      a substantially increased endurance time (reduced fatigability) at a low force
      (20% MVC) and no statistical effect at a moderate force (65% MVC). Despite
      atrophy of the elbow flexor muscles due to the immobilization, the twitch force
      elicited in biceps brachii by electrical stimulation was greater after
      immobilization. The selective improvement of fatigue resistance for the low-force
      contraction and the absence of a change in the time course of the twitch suggests
      that the immobilization-induced adaptations included an improved efficacy of some
      excitation-contraction processes and underscored the major role of these
      mechanisms in determining the endurance time for low-force, long-duration
      contractions.

PMID- 9179576
TI  - Anaerobic energy production in human skeletal muscle in intense contraction: a
      comparison of 31P magnetic resonance spectroscopy and biochemical techniques.
AB  - Five subjects underwent twenty electrically evoked maximal isometric contractions
      of the anterior tibialis muscle of both legs (n = 10), with limb blood flow
      occluded. Measurements of muscle high-energy phosphates (ATP, ADP and
      phosphocreatine (PCr)), lactate and pH were made using both 31P magnetic
      resonance spectroscopy (MRS) and the biochemical analysis of biopsy samples
      obtained from directly below the MRS surface coil. The resting PCr concentration
      determined using MRS was similar to that measured in the biopsy material.
      Following contraction, MRS showed a greater decrease in ATP concentration
      compared with biochemical analysis (P < 0.05), but the decrease in PCr was
      similar. Good agreement was found when comparing resting muscle pH estimated by
      the two methods. Post-exercise muscle pH was, however, consistently lower with
      MRS and consequently the accumulation of muscle lactate estimated using MRS was
      markedly greater than the corresponding biochemical measurement (P < 0.05). As a
      result, MRS revealed an approximately 30% greater anaerobic ATP turnover during
      contraction, although this just failed to reach statistical significance (P >
      0.05). The results of the present study indicate that there is little difference
      in the muscle concentration of PCr estimated by the two methods, but that there
      are differences in the estimates of ATP, pH and lactate changes during
      contraction. This latter discrepancy may lead to greater estimates of ATP
      turnover being made as a result of MRS analysis.

PMID- 9179577
TI  - Glycosaminoglycan depletion greatly raises the hydraulic permeability of rabbit
      joint synovial lining.
AB  - The hydraulic resistance of the synovial lining of a joint is important for
      retention of intraarticular lubricant. The resistance has been attributed to
      synovial interstitial glycosaminoglycans. This was tested by depletion of
      hyaluronan and chondroitin sulphates from synovium in five rabbit knees in vivo
      under anaesthesia, using testicular hyaluronidase. The enzyme raised synovial
      permeability to fluid 5- to 7-fold-substantially more, in fact, than predicted by
      a recent model. The results prove that hyaluronan and/or chondroitin sulphate are
      important sources of hydraulic resistance in synovium.

PMID- 9179578
TI  - The impact of the Postponing Sexual Involvement curriculum among youths in
      California.
AB  - Postponing Sexual Involvement (PSI) is a widely implemented middle school
      curriculum designed to delay the onset of sexual intercourse. In an evaluation of
      its effectiveness among seventh and eighth graders in California, 10,600 youths
      from schools and community-based organizations statewide were recruited and
      participated in randomly assigned intervention or control groups; the curriculum
      was implemented by either adult or youth leaders. Survey data were collected
      before the program was implemented, and at three months and 17 months afterward.
      At three months, small but statistically significant changes were found in fewer
      than half of the measured attitudes, behaviors and intentions related to sexual
      activity; at 17 months, none of these significant positive effects of the PSI
      program had been sustained. At neither follow-up were there significant positive
      changes in sexual behavior; Youths in treatment and control groups were equally
      likely to have become sexually active, and youths in treatment groups were not
      less likely than youths in control groups to report a pregnancy or a sexually
      transmitted infection. The evaluation suggests that PSI may be too modest in
      length and scope to have an impact on youths' sexual behavior.

PMID- 9179579
TI  - Education Now and Babies Later (ENABL): life history of a campaign to Postpone
      Sexual Involvement.
AB  - Education Now and Babies Later (ENABL), a statewide adolescent pregnancy
      prevention initiative, was inaugurated in California in June 1992. Developed by
      the state's Office of Family Planning, ENABL utilized a five-session intervention
      curriculum, Postponing Sexual Involvement (PSI), targeted at delaying the onset
      of sexual activity among youths aged 12-14. Schoolwide and community-based
      activities, along with a statewide media and public relations campaign,
      reinforced the intervention's message. Data collected from nearly 9,000 surveys,
      75 individual interviews and 50 focus groups indicated that youths, parents and
      community representatives supported the initiative and endorsed its message,
      although most recommended changes to the curriculum. However, because no impact
      on sexual behavior could be demonstrated, the campaign was abruptly terminated in
      February 1996, despite recommendations that the program be retained and improved.

PMID- 9179580
TI  - Teenage abortion and pregnancy statistics by state, 1992.
AB  - In 1992, 112 pregnancies occurred per 1,000 U.S. women aged 15-19; of these, 61
      ended in births, 36 in abortions and 15 in miscarriages. Black teenagers' rates
      of pregnancies, births and abortions were 2-3 times those of whites; Hispanic
      teenagers had rates of births and abortions between those of blacks and whites.
      While similar proportions of pregnant black and non-Hispanic white teenagers had
      abortions (40% and 38%, respectively), the proportion was lower among Hispanics
      (29%). Among all women 15-19, the birthrate rose 12 points between 1987 and 1991;
      one-third of the rise (four points) may be attributable to a fall in the abortion
      rate. Between 1991 and 1995, the birth rate of black teenagers fell from 116 to
      96 per 1,000, a level well below that of Hispanics (106 per 1,000). Among the
      states, pregnancy rates per 1,000 teenagers in 1992 ranged from 159 (in
      California) to 59 (in North Dakota), birth rates per 1,000 varied from 84
      (Mississippi) to 31 (New Hampshire) and abortion rates per 1,000 ranged from 67
      (Hawaii) to nine (Utah). The pregnancy rates of white and black teenagers are
      negatively correlated.

PMID- 9179581
TI  - Does condom availability make a difference? An evaluation of Philadelphia's
      health resource centers.
AB  - In 1992, nine Philadelphia high schools opened drop-in centers where students
      could receive reproductive health information, condoms and general health
      referrals. Analyses of survey data collected in 1991 and 1993 suggest that the
      presence of the condom availability program did not increase the level of sexual
      activity among students in these schools and may have contributed to safer sex
      practices. The proportion of students who had used a condom at last intercourse
      increased from 52% to 58%; although the change was not statistically significant,
      it exceeded the increase in a group of comparison schools. Changes in the
      proportions of students who had ever had intercourse, who had had sex in the
      previous four weeks, who had used a condom at last intercourse and who had
      recently had unprotected sex were greatest in schools with higher levels of
      program usage; however, only the decline in recent unprotected intercourse among
      students in high-use schools (from 14% to 6%) approached statistical
      significance.

PMID- 9179582
TI  - Young men's experience with condom breakage.
AB  - In a nationally representative sample of men aged 17-22, 23% of those using
      condoms reported experiencing at least one condom break during the previous 12
      months. Of all condoms used, 2.5% had broken. In multivariate analyses, increased
      experience with condoms reduced the likelihood of experiencing condom breakage.
      Recent sex education was associated with an almost 80% decrease in the risk of
      breakage among young men who used condoms infrequently. Young males who had ever
      had a sexually transmitted disease (STD), or whose sexual partner had had an STD,
      were almost three times as likely as other respondents to have experienced condom
      breakage. In addition, young men with a household income of less than $60,000
      were 2-3 times as likely to have broken a condom as were those with a higher
      household income.

PMID- 9179583
TI  - The association between substance use, condom use and sexual risk among low
      income women.
AB  - Substance use is frequently assumed to be associated with higher levels of sexual
      risk-taking and lower levels of condom use. An analysis of 668 black, Hispanic
      and white low-income women at public health and public assistance facilities in
      Miami show that 19% engaged in risky sexual behavior over the preceding six
      months, 24% in substance use and 31% in condom use. Overall, substance users are
      nearly four and one-half times more likely to take sexual risks than nonusers,
      but are about half as likely to have relied on condoms. When the probability of
      condom use is considered in the context of both substance use and sexual risk,
      substance users who take sexual risks appear just as likely to rely on condoms as
      are nonusers who take sexual risks and those who do not (odds of 0.43-0.49).
      However, substance users who do not take sexual risks are much less likely to use
      condoms (odds of 0.15). This pattern holds among black, Hispanic and white women,
      and suggests that perceptions of risk and the risks that partners bring to sexual
      encounters may be more important determinants of condom use than substance use
      per se.

PMID- 9179584
TI  - Economic correlates of nonmarital childbearing among adult women.
AB  - The growth of nonmarital childbearing among women who are beyond their teenage
      years is well documented. Very little is known, however, about the economic
      status of these women. Data for 1991 from the nationally representative Panel
      Study of Income Dynamics indicate that the socioeconomic status of women who have
      had a nonmarital birth as an adult is similar to that of women who had a birth as
      an adolescent: They have similar median income-to-needs ratios (2.29 vs. 2.17),
      and similar rates of poverty (20% vs. 23%) and welfare receipt (22% vs. 19%).
      Women who have had both teenage and postteenage nonmarital births fare
      particularly poorly: Their median family income is $11,280; nearly half receive
      welfare; and 55% are officially poor. However, women who first gave birth as
      adolescents but have not had subsequent nonmarital births do reasonably well:
      Fewer than 10% receive welfare, and their median income-to-needs ratio is 2.6.

PMID- 9179586
TI  - Roles of purine nucleotides and adenosine in enhancing NOS II gene expression in
      interleukin-1 beta-stimulated rat vascular smooth muscle cells.
AB  - The production of nitric oxide (NO) by vascular smooth muscle cells (VSMC) is
      stimulated by interleukin-1 beta (IL-1 beta). This is enhanced in a dose
      dependent manner by ADP, although it alone failed to induce nitrite accumulation.
      Purine nucleotides and their nonhydrolizable analogues as well as adenosine also
      exhibit variable enhancing effects. This enhanced nitrite formation was due to
      induction of the NO synthase (NOS II) gene as judged by Northern hybridization
      using an NOS II specific probe and by Ca2+ independency of the NOS II activity. 8
      (p-Sulfophenyl)-theophylline, a blocker of adenosine receptors, suppressed the
      enhanced NO production by adenosine and ADP to the level of that with IL-1 beta
      alone. These data indicate that activation of the adenosine receptor on VSMC may
      enhance production of NOS II by modulating a signal transducing pathway of IL-1
      beta. Although cAMP is a candidate as the second messenger, it was not
      significantly elevated by either ADP or adenosine treatment in IL-1 beta
      stimulated cells. This mechanism might be stimulated under conditions with
      release of various purine and their derivatives.

PMID- 9179585
TI  - Effect of purine nucleoside phosphates on OH-radical generation by reaction of
      Fe2+ with oxygen.
AB  - The influence of various purine nucleotides, nucleosides and nucleoside
      phosphates on the generation of OH-radicals by the reaction of Fe2+ with oxygen
      was investigated. Coumarin-3-carboxylic acid was used as a fluorescent detector
      of OH.. Nucleoside triphosphates caused the enhancement of OH. production due to
      chelation of ferrous ion by the phosphate moiety. About 30% of produced OH. are
      intramolecularly scavenged by the nucleoside moiety of the chelator molecule.
      Nucleoside diphosphates cause a slight enhancement of OH. yield. Nucleotides,
      nucleosides and nucleoside monophosphates decrease the OH. production. Rate
      constants of reaction between OH. and nucleoside derivatives were determined from
      the competitive scavenging of OH radicals, produced by oxidation of Fe(2+)-EDTA
      complex. Derivatives of guanosine and xanthine are more efficient scavengers in
      comparison to adenine and inosine. Phosphate groups do not affect the constant of
      reaction of nucleoside with OH.. Our results suggest that the yield of OH. in the
      presence of the nucleotide derivatives is determined by chelation of ferrous with
      polyphosphates and preferential OH. scavenging by the organic portion of
      molecule. We propose that the generation of active oxygen intermediates in the
      reaction between nucleoside triphosphate complexes of iron and molecular oxygen
      is involved in iron-related cellular injury.

PMID- 9179587
TI  - Antioxidant activity of reduced menadione in solvent solution and in model
      membranes.
AB  - The antioxidant activity of reduced menadione was investigated and compared with
      that of alpha-tocopherol both in solvent solution and in large unilamellar
      vesicles by using azocompounds as free radical generators. The results show that:
      i) reduced menadione behaves as a chain-breaking antioxidant; ii) its inhibition
      rate constant is similar to that of alpha-tocopherol in homogeneous solution,
      whereas it is 4 times larger in egg yolk lecithin vesicles; iii) the
      stoichiometric factor is found lower than 1 in both systems, since a substantial
      portion of menadiol is consumed by autoxidation and does not contribute to
      radical trapping; iv) when both alpha-tocopherol and menadiol are present in
      vesicles, reduced menadione can spare alpha-tocopherol. Data presented here
      suggest that the reduced form of vitamin K may protect, when present, cellular
      membranes from free radical damage.

PMID- 9179588
TI  - Mitochondrial respiratory chain features after gamma-irradiation.
AB  - Radiation provokes damage to DNA but also to membrane and protein structure.
      Radiolysis is a tool used very often in the study of free radical biological
      effects and of scavenger molecules effectiveness. Nitroimidazoles have been
      demonstrated to enhance the radiation effects on biological structures. The
      studies we have performed on isolated mitochondria irradiated, with and without
      nitroimidazoles, at a radiation dose equal to LD90, indicate that this treatment
      is not able to affect the structural and functional features investigated
      (ubiquinone-10, fatty acids, respiratory cytochrome levels or membrane fluidity
      and respiratory enzymatic activities), suggesting that an involvement of such
      externally produced radicals on membrane damage is unlikely. Moreover it was
      ascertained that the mitochondrial redox activities do not take part into the
      intracellular nitroimidazole reduction.

PMID- 9179589
TI  - Plasma peroxyl radical trapping capacity in lung cancer patients: a case-control
      study.
AB  - Increasing evidence suggests that cancer patients express oxidative disturbances.
      The main objective of this cross-sectional case-control study (n = 57 + 76) was
      to explore whether lung cancer patients, when compared to healthy controls, have
      alterations in their plasma peroxyl radical trapping capacity (TRAP). Group
      matching was used with respect to age, sex and smoking history. A secondary
      objective was to observe the effects of life-long cigarette consumption on plasma
      TRAP and its components. Mean TRAP values were significantly lower in the cancer
      patients than in the control group (1143 vs 1273 mumol/l, p = 0.0002). Moreover,
      all the components of TRAP (except uric acid) were significantly lower in the
      cancer group: protein SH-groups 442 vs 571 mumol/l, ascorbic acid 34.0 vs 46.5
      mumol/l and vitamin E 25.0 vs 33.8 mumol/l. The as yet unidentified antioxidant
      compounds in plasma contributed 26.5% of plasma TRAP in the cancer group and
      30.2% in the control group. There was no correlation between cigarette
      consumption in pack-years and plasma TRAP; however, plasma concentrations of uric
      acid and ascorbic acid were negatively correlated with cigarette consumption.

PMID- 9179590
TI  - A comparison between different methods for the determination of reduced and
      oxidized glutathione in mammalian tissues.
AB  - In this study, three rapid assay techniques for the determination of glutathione,
      one enzymatic, one fluorometric and one newly patented colorimetric method, were
      compared by measuring reduced (GSH) and oxidized (GSSG) glutathione in guinea-pig
      heart and liver. The HPLC technique was used as a standard, since it is
      considered the most reliable assay method. In heart, all methods measured the
      same levels of GSH (about 1 mumole/g wet tissue), whereas in liver the
      fluorometric assay gave GSH levels about half as high as those measured by the
      other methods (about 3 vs. 7 mumoles/g wet tissue). Conversely, the fluorometric
      assay grossly overestimated GSSG concentration (by 5 to 8 times) in both heart
      and liver. These results confirm previous doubts about the use of the
      fluorometric technique for GSSG determination in mammalian tissues and also raise
      some questions about its use for the measurement of GSH in liver. In this tissue,
      the GSH concentration determined by the fluorometric method was shown to be
      inversely correlated with the size of the sample, suggesting the presence of some
      quenching material.

PMID- 9179591
TI  - Protein oxidation of a hair sample kept in Alaskan ice for 800-1000 years.
AB  - Ancient finds of organic matter are not only of the highest value for
      palaeochemists and palaeobiologists but can be used to determine basic chemical
      reactions, such as protein oxidation, over long time periods. We studied
      oxidation of human hair protein about one thousand years old of an Alaskan child
      buried in ice, ten hair samples of copts of comparable age buried in graves of
      hot dry sand and compared the results to ten recent hair samples. Protein
      oxidation parameters o-tyrosine and cysteic acid of the Alaskan child were
      comparable to recent samples whereas they were higher in the coptic specimen. N
      epsilon-carboxymethyllysine, a parameter for glycoxidation, however, was as high
      in coptic specimen. We conclude that ice in contrast to soil prevented protein
      oxidation but failed to inhibit glycoxidation, a reaction initiated by
      autooxidation of glucose. This study therefore has implications for the
      interpretation of oxidation and glycoxidation as well as preservation mechanisms
      of proteins.

PMID- 9179592
TI  - The transcription of liver thioredoxin following the ionizing irradiation of
      radioresistant and radiosensitive mice.
AB  - The radiation protective effect of thioredoxin (TRX) in a bacterial system has
      been reported and based upon this observation we were interested to examine TRX
      transcription in the mammalian system following ionizing irradiation. In order to
      answer the question whether radiation sensitive mice (BALB/c) showed TRX
      transcription different from radiation resistant mice (C3H), we exposed these
      strains to X-ray doses of 2 Gy, 4 Gy and 6 Gy. Groups consisting of 6 mice were
      sacrificed 5, 15 and 30 minutes after irradiation and livers were immediately
      taken into liquid nitrogen. Total RNA was isolated from the organs by the use of
      a commercially available kit and used for Northern blots and slot blots with a
      chemiluminescence technique. Northern blots revealed a single band at 538 bp for
      TRX and at 1.8 kb for beta-actin. Quantification of mRNA TRX by densitometry of
      slot blots revealed that C3H transcribed TRX significantly higher at an earlier
      time point (5 min) than BALB/c. This delayed transcription of TRX in the
      radiosensitive mouse strain showed a comparable pattern at three different
      radiation doses and may well be responsible for radioresistance although no
      quantitative differences of TRX transcription between BALB/c and C3H mice were
      detectable.

PMID- 9179593
TI  - Antioxidant activities of some extracts of Thymus zygis.
AB  - The antioxidant activities of methanol and ethyl ether extracts obtained from
      Thymus zygis, collected during the flowering or non-flowering period, were
      evaluated and compared. To investigate this potential, extracts were tested on
      their capacity to react with diphenylpicrylhydrazyl (DPPH) in a homogeneous
      medium, and to inhibit Fe2+/ascorbate-induced membrane lipid peroxidation, as
      estimated by the formation of thiobarbituric acid-reactive substances (TBARS).
      Although methanol extracts reduce DPPH radicals more efficiently than ethyl ether
      extracts, suggesting a potent radical scavenger activity, the ethyl ether
      extracts were found to be most active in inhibiting lipid peroxidation in
      sarcoplasmic reticulum (SR) membranes. In addition, both extracts present peroxyl
      and superoxide radical scavenging activities. Peroxyl radicals were generated by
      the water soluble 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)
      azoinitiator, and the scavenging activities of the extracts were measured by the
      inhibition of cis-parinaric acid (PnA) fluorescence decay in SR. Superoxide
      radicals were generated either by an enzymatic or a non-enzymatic system, and the
      scavenger ability was evaluated by the inhibition of nitroblue tetrazolium
      reduction. Methanolic extracts are more potent as scavengers of peroxyl and
      superoxide radicals than the ethyl ether extracts. Apparently, there is a
      relationship between antioxidant potency and the total phenolic groups content in
      each extract.

PMID- 9179594
TI  - The expression of the low affinity nerve growth factor receptor in long-term
      denervated Schwann cells.
AB  - Schwann cells in the distal stump of injured peripheral nerves synthesize the low
      affinity nerve growth factor receptor (p75). In this study we used short-term (1
      week) and long-term (1-12 months) transected distal sciatic nerves of rats to
      determine the variations of p75 expression by using immunocytochemistry and in
      situ hybridization. Semi-quantitative analysis revealed that the synthesis of the
      protein product of the p75 gene is rapidly enhanced to reach a peak within the 1
      month after denervation. After that it gradually decreased and was barely
      detectable 6 months following denervation. Double immunocytochemistry for p75 and
      the S100 protein revealed that p75 immunoreactivity is confined to the Schwann
      cells. Quantitative analysis of our in situ hybridization experiments revealed
      that the upregulation of the p75 mRNA parallels the enhanced synthesis of the
      corresponding protein and reaches a peak within 1 month, which is maintained
      until the second month after the transection and declines thereafter to reach
      background levels at 4 months. The electron microscopic observations reveal that
      the increase in the number of nuclei in the distal stump belong to severely
      atrophied Schwann cells and fibroblasts. Since the presence of p75 in the Schwann
      cells is necessary for reinnervation, our results indicate that, based on the
      expression of p75, the Schwann cells will provide a most suitable environment for
      the regenerating axons up to the first month. At later stages the ability of the
      Schwann cells to synthesize p75 and cell adhesion proteins such as N-CAM and GAP
      43 decreases which may be one of the factors that contribute to poor functional
      recovery if the regenerating axons reach the distal stump after long periods of
      time.

PMID- 9179595
TI  - Oligodendrocytes express gap junction proteins connexin32 and connexin45.
AB  - Oligodendrocytes, the myelin-forming glia of brain, are connected by gap
      junctions in situ and in culture. Cultured oligodendrocytes from adult bovine and
      porcine brains were studied using immunocytochemical, molecular, and
      electrophysiological techniques in order to characterize the gap junction types.
      The expression of connexin32 was substantiated by the detection of low, but
      significant, signals using connexin-specific probes in Northern and Western blot
      analyses. Connexin43, which comprises gap junctions in astrocytes, was not
      detectable in pure oligodendrocytic cultures; mRNAs of connexin40 and connexin37
      and connexin26 were also not detected. By means of two specific antibodies
      directed to the recently cloned connexin45 and by RT-PCR we were able to identify
      this connexin as a second oligodendrocytic gap junction protein. Whole cell
      voltage clamp recording provided evidence for electrical coupling between pairs
      of cultured oligodendrocytes (mean junctional conductance 3.9 nS, n = 38 pairs)
      and intracellular Lucifer Yellow injection indicated that oligodendrocytes were
      usually only weakly dye coupled, with spread generally being restricted to
      nearest neighbors. Unitary conductances ranged from > 20 to < 150 pS with modes
      of distribution at about 100 to 120pS and 40 to 20 pS, respectively. These
      unitary conductances are consistent with the channel events expected for
      connexin32 and connexin45. The low degree of functional coupling between
      oligodendrocytes in vitro corresponds with the low levels of connexin32 and
      connexin45 messenger RNAs and protein expression.

PMID- 9179596
TI  - Removal of retrogradely transported material from rat lumbosacral alpha-motor
      axons by paranodal axon-Schwann cell networks.
AB  - The aim of this study was to investigate the potential ability of Schwann cells
      to sequester axonally transported material via so called axon-Schwann cell
      networks (ASNs). These are entities consisting of sheets of Schwann cell adaxonal
      plasma membrane that invade the axon and segregate portions of axoplasm in
      paranodes of large myelinated mammalian nerve fibres. Rat hindlimb alpha-motor
      axons were examined in the L4-S1 ventral roots using light/fluorescence, confocal
      laser, and electron microscopy for detection of retrogradely transported red
      fluorescent latex nanospheres taken up at a sciatic nerve crush, and
      intramuscularly injected horseradish peroxidase endocytosed by intact synaptic
      terminals. Survival times after tracer administration ranged from 27 hours to 4
      weeks. During their retrograde transport toward the motor neuron perikarya,
      organelles carrying nanospheres/peroxidase accumulated at nodes of Ranvier, where
      they often appeared in close association with the paranodal myelin sheath. Serial
      section electron microscopy showed that many of the tracer-containing bodies were
      situated within ASN complexes, thereby being segregated from the main axon. Four
      weeks after nanosphere administration, several node-paranode regions still showed
      ASN-associated aggregations of spheres, some of which were situated in the
      adaxonal Schwann cell cytoplasm. The data establish the ability of Schwann cells
      to segregate material from motor axons with intact myelin sheaths, using the ASN
      as mediator. Taken together with our earlier observations that ASNs in alpha
      motor axons are also rich in lysosomes, this process would allow a local
      elimination and secluded degradation of retrogradely transported foreign
      substances and degenerate organelles before reaching the motor neuron perikarya.
      In addition, ASNs may serve as sites for disposal of indigestable material.

PMID- 9179597
TI  - Identification of the delayed rectifier potassium channel, Kv1.6, in cultured
      astrocytes.
AB  - Astrocytes are an abundant glial cell type of the central nervous system that
      appear to play a role in regulating extracellular potassium concentrations in
      brain, thereby contributing to the maintenance of normal neuronal activity.
      Voltage-gated potassium conductances, shown to be present in astrocytes, may be
      involved in this and other astrocytic functions. Toward defining the role of
      voltage-gated potassium channels in astrocytes, total RNA prepared from cultured
      mouse cortical astrocytes was screened, using a reverse transcriptase-polymerase
      chain reaction (RT-PCR) approach, for the expression of several members of the
      Shaker-like potassium channel subfamily (Kv1.1-Kv1.6). A relatively high level of
      Kv1.6 transcript was identified by RT-PCR and then confirmed and quantitated by
      ribonuclease protection assays using a Kv1.6-specific riboprobe.
      Immunocytochemical staining showed double-labeling of glial fibrillary acidic
      protein-positive cells with antibody specific for the Kv1.6 channel. The Kv1.6
      protein expression was variable among the individual astrocytes. Outward voltage
      gated currents were studied in astrocytes in primary culture using the Nystatin
      perforated patch voltage clamp technique. Outward potassium currents were
      observed in all cells studied, and this current was partially blocked by
      perfusion with 100 nM dendrotoxin (DTX) in 14 of 16 cells tested. This DTX
      sensitive current appeared to be a sustained outward potassium current,
      consistent with the suggestion that the Shaker-like potassium channel Kv1.6
      underlies a portion of the delayed rectifier potassium current in cultured mouse
      cortical astrocytes.

PMID- 9179598
TI  - Regulation of aldose reductase expression in rat astrocytes in culture.
AB  - Aldose reductase (AR) is known to be responsible for many side effects of
      diabetes. In the present work, we studied the effects of various extracellular
      signals on the regulation of the expression of AR in astrocytes in culture, by
      determining its enzymatic activity or its mRNA level. We found that basic
      fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF),
      epidermal growth factor (EGF), and hypertonic NaCl were able to increase the
      expression of AR in astrocytes. A superinduction was found when bFGF was combined
      with hypertonicity. We also observed that AR activity was independent of glucose
      concentration in the culture medium. However, when the concentration of glucose
      in the culture medium was under 1 g/l, bFGF did not increase the activity of AR.
      Thus, when glucose is depleted, the regulation of AR expression by bFGF does not
      operate. In addition, AR does not seem to be involved in control of astrocyte
      proliferation, in contrast to the effects reported on other cell types. These
      results indicate that AR is expressed in astrocytes and that its expression is
      upregulated by hypertonicity but also by FGFs and EGF. This suggests that in
      these cells, AR elicits some regulatory functions.

PMID- 9179599
TI  - Astrocytes and microglial cells incorporate degenerating fibers following
      entorhinal lesion: a light, confocal, and electron microscopical study using a
      phagocytosis-dependent labeling technique.
AB  - Entorhinal lesion leads to anterograde degeneration of perforant path fibers in
      their main termination zone in the outer molecular layers of the dentate gyrus.
      Concomitantly, astrocytes become hypertrophic, and microglial cells alter their
      phenotype, suggesting participation in anterograde degeneration. This study
      analyzes the involvement of these lesion-induced activated glial cells in the
      process of phagocytosis of degenerated axonal debris. We established a
      phagocytosis-dependent labeling technique that allows for direct and simultaneous
      visualization of both labeled incorporated axonal debris and incorporating glial
      cells. Stereotaxic application of small crystals of the biotin- and rhodamine
      conjugated dextran amine Mini Ruby (MR) into the entorhinal cortex led to strong
      and stable axonal staining of perforant path axons. Following entorhinal lesion,
      labeled terminals and fibers condensed and formed small granules. Incorporation
      of these rhodamine-fluorescent granules resulted in a phagocytosis-dependent cell
      labeling. During the first 3 days, we were able to identify these cells as
      microglia by using double-fluorescence and confocal microscopy. The first
      unequivocally double-labeled astrocytes were found 6 days post lesion (dpl).
      Whereas in all stages a subpopulation of microglial cells remained devoid of MR
      labeled granules, all astrocytes in the middle molecular layer were double
      labeled after long survival times (20 dpl). On the ultrastructural level, labeled
      granules appeared to be perforant path axons containing the tracer. Both
      terminals and myelinated fibers could be seen inside the cytoplasm of microglial
      cells and astrocytes. Thus, anterograde degeneration is a sufficient stimulus to
      induce axon incorporation by both astrocytes and a subpopulation of microglial
      cells.

PMID- 9179600
TI  - Neuronal dependency of the glycine transporter GLYT1 expression in glial cells.
AB  - Two membrane-localized transporter proteins (GLYT1 and GLYT2) are responsible for
      removal of extracellular glycine in the mammalian CNS. Whereas GLYT1 seems to be
      expressed mainly in glial cells, GLYT2 is neuronal. The highest concentrations of
      both transporters are found in glycinergic areas of the nervous system. The
      expression of these proteins may be under regulatory control. We demonstrate here
      that GLYT1 is not expressed in pure glial cultures, but it is expressed by
      diverse types of glial cells in mixed neuronal/glial cultures. In these mixed
      cultures, the glial expression of GLYT1 is down-regulated after selective
      elimination of the neurons. The absence of expression in pure glial cultures and
      the observed reduction in the GLYT1 expression after neuronal loss support the
      existence of a regulatory cross-talk between neurons and glia to initiate and
      sustain the glial expression of GLYT1.

PMID- 9179601
TI  - Bovine serum albumin and lysophosphatidic acid stimulate calcium mobilization and
      reversal of cAMP-induced stellation in rat spinal cord astrocytes.
AB  - We report that lysophosphatidic acid (LPA) stimulates dynamic calcium (Ca2+)
      fluctuations and morphological rearrangements in astrocytes derived from neonatal
      rat spinal cord. Addition of 10 microM LPA elicited single Ca2+ transients, or
      biphasic oscillations and sustained increases in intracellular Ca2+ ([Ca2+]i).
      The biphasic Ca2+ response consisted of an initial release from intracellular
      stores, often followed by a sustained elevation or continued oscillations that
      required Ca2+ flux across the cell membrane. The type of Ca2+ response, but not
      the overall magnitude, was dependent on LPA concentration. Higher concentrations
      (> 10 microM) often elicited sustained increases in [Ca2+]i, while lower
      concentrations stimulated oscillations or single Ca2+ transients. It has
      previously been established that agents that elevate cyclic adenosine
      monophosphate (cAMP) induce flat astrocytes to adopt a more stellate morphology.
      LPA can completely reverse this morphological change at a half-maximal
      concentration of 215 nM. Inhibiting LPA-induced [Ca2+]i fluctuations using BAPTA
      AM to buffer [Ca2+]i and EGTA in the bath to prevent transmembrane flux had
      little effect on the ability of LPA to reverse stellation. LPA is found bound to
      serum albumin, in which crude preparations have been shown to induce various
      physiological responses in a number of cell types. Many of the activities have
      been attributed to albumin-associated lipid factors including LPA. We show that
      lipid factors associated with BSA can mimic the effect of LPA in both Ca2+
      mobilization and reversal of cAMP-induced stellation.

PMID- 9179603
TI  - Involvement of enhanced coagulation and fibrinolysis system in induction of
      atherosclerosis in hyperlipidemic rabbits fed on a high cholesterol diet.
AB  - We studied the involvement of coagulation and fibrinolysis system in the
      induction and development of atherosclerosis in rabbits with hyperlipidemia
      induced by a high-cholesterol diet (HCD). In HCD rabbits, plasma lipids and
      atherogenic indices were maintained at a high level throughout the experimental
      period compared with those in rabbits fed on a standard diet. In the early phase,
      a significant increase in fibrinogen level was followed by increases in the
      activities of plasminogen and tissue-type plasminogen activator with a decrease
      in alpha 2-plasmin inhibitor activity and platelet count. In the middle and late
      phases, significant increases in plasminogen activator inhibitor-1 and
      antithrombin-III were observed in HCD rabbits. These results suggest that the
      early enhancement of coagulation followed by high activity of fibrinolysis is
      involved in the induction and development of hyperlipidemic thromboembolism and
      atherosclerosis in HCD rabbits.

PMID- 9179604
TI  - Interleukin-12, an emerging anti-tumour cytokine.
AB  - Interleukin 12 is a multifunctional cytokine secreted by a wide variety of cells
      including macrophages and B cells and promotes cell-mediated immunity by its
      ability to selectively augment Th-1 type immune responses. This pleiotropic
      cytokine exerts numerous effects on T and NK cells, resulting in an enhancement
      of cytolytic activity and direct stimulation of IFN-gamma production and studies
      have demonstrated that this cytokine plays an important role in the promotion of
      the host resistance to infection by bacterial, fungal and protozoan pathogens. IL
      12 has also been shown to cause tumour regression and reduce metastasis in animal
      models, due to both the promotion of antitumour immunity and also to the
      significant inhibition of angiogenesis and up-regulation of E-cadherin, a
      metastasis suppressor. Recent reports using local administration of IL-12 to the
      tumour site by retroviral vectors and 'gene gun' techniques have resulted in a
      significant reduction of tumour mass, with complete eradication occurring in
      several cases. The effects of IL-12 in patients with cancer are currently under
      investigation. Thus, interleukin-12 represents a cytokine with potent antitumour
      effects and may therefore be an attractive agent in anticancer therapy.

PMID- 9179602
TI  - Comparison of urinary component levels in 4 strains of mice with different
      physiological characteristics.
AB  - Changes in urinary component levels before, during and after reproduction were
      examined with 1H-nuclear magnetic resonance (NMR) in four strains of female mice
      with different mammary tumour potential and related characteristics (SHN, SLN,
      GR/A and C3H/He). Regardless of the variations in these changes among the
      strains, the urinary component levels reflected physiological changes during
      reproduction and some strain-specific characteristics. The urinary excretion of
      citrate, 2-oxoglutarate and lactate increased from the virginal stage to
      pregnancy and declined during lactation in all strains, indicating a marked
      change in sugar metabolism during reproduction. SHN and SLN, which are from the
      same basal stock, showed a similar pattern and the level, of several components
      were lower than those of GR/A and C3H/He. The levels of some lower components
      were compensated for by higher urine excretion. The levels of taurine and
      betaine, both essential for fetal and pup growth, increased at lactation in only
      GR/A, reflecting the poorer pup growth observed in this strain. Finally, the 1H
      NMR method was useful to estimate not only the metabolic but also the
      physiological changes of the animals without invasion, pain or distress and would
      thus contribute to animal welfare in the animal experiments.

PMID- 9179605
TI  - Hemodynamic and metabolic effects of intravenous formyl-methionyl-leucyl
      phenylalanine (FMLP) in rabbits.
AB  - We have studied the role of neutrophils and the effects of the chemotactic factor
      FMLP, using normal, neutropenic (after cyclophosphamide treatment) and C5a desArg
      treated unanesthetized rabbits. The intravenous administration of FMLP in normal
      animals induces transient and dose-dependent hypotension, neutropenia and
      thrombocytopenia, with a maximal response in 3 minutes. When a bolus of 5 x 10(
      9) moles FMLP was administered, maximal arterial hypotension (40 +/- 1.1 v.s. 90
      +/- 1.1 mmHg in the controls, P < 0.001) accompanied by a significant increase in
      central venous pressure (0.89 +/- 0.9 v.s. -2.2 +/- 0.7 mmHg in the controls, P <
      0.01) and a decrease in systemic vascular resistance (90 +/- 15.6 v.s 187 +/-
      16.4 mmHg/L/min, P < 0.005). Plasma pH and bicarbonate were significantly
      reduced, with a parallel increase in plasma lactate levels. A similar reduction
      of arterial blood pressure was also noted in neutropenic animals (31 +/- 3% of
      pretreatment levels respectively). C5a des Arg caused neutropenia similar to that
      seen after 5 x 10(-9) moles FMLP (120 +/- 60/mm3 and 170 +/- 25/mm3
      respectively), but it did not induce hypotension. These data suggest that simple
      neutrophil activation is not the mechanism of the FMLP-induced hypotension and
      that this chemotactic factor may interact with other cell types to produce its
      effects.

PMID- 9179606
TI  - Transmodulation of EGF receptor by interferon-gamma in human hepatocellular
      carcinoma HepG2 cells.
AB  - EGF receptor has been recognized to playing an important role in the regulation
      of normal and tumor cell growth. In this study, the transmodulatory effect of IFN
      gamma on EGF receptor of human hepatocellular carcinoma cell line HepG2 was
      investigated. The results demonstrated that IFN gamma was able to modulate EGF
      receptor of HepG2 cells by enhancing the tyrosine phosphorylation of the
      receptor. However, the effect appeared only if EGF was present, but not mediated
      by IFN gamma alone. No significant alteration was found in terms of the
      expression or the affinity of EGF receptor when HepG2 cells were treated with IFN
      gamma. In addition, EGF internalization in the cells was also not affected.
      Because IFN gamma is an inhibitory agent for the growth of HepG2 cells, this
      transmodulatory effect of IFN gamma on the tyrosine phosphorylation of EGF
      receptor might be associated with the inhibition of the growth of HepG2 cells.

PMID- 9179607
TI  - Influence of stage classification, tumor differentiation and mode of invasion
      against clinical and histopathological effects on low dose sequential
      methotrexate and 5-fluorouracil administration as neo-adjuvant chemotherapy for
      oral squamous cell carcinoma.
AB  - We report on the influences of stage classification, tumor differentiation and
      mode of invasion against clinical and histopathological effects associated with
      low dose sequential methotrexate (MTX) and 5-fluorouracil (5-FU) (MF therapy) as
      neo-adjuvant chemotherapy in oral cancer. The oral cancer of 22 patients was
      treated as follows: MTX (75 mg/body) was administrated by intravenous infusion
      for 1 hour, followed by 5-FU (500 mg/body) intravenous infusion for 2 hours on
      Day 1, MTX (75 mg/body) intravenous infusion for 1 hour on Day 4, and parenteral
      dose of leucovorin on Day 2 and Day 5. The MF therapy of 1-5 courses was
      performed weekly or every 2 weeks. The clinical response rate was lower in stage
      IV than in the other stages. There was no difference in the rate of tumor
      differentiation by WHO grade classification, I and II. The rate was higher in
      grade 1, 2 and 3 than in grade 4C and 4D due to mode of invasion. The
      histological response rate was higher in stage I and II than in stage III and IV.
      The response rate was higher in grade II than in grade I, but was higher in grade
      1 and 2 than in grade 3 and 4C. However, the response rate in grade 4D was good
      (66.7%; 2/3). Histological response was demonstrated only in partial or complete
      response cases of the clinical response. MF therapy was suggested to be effective
      for histological response regardless of stage classification, tumor
      differentiation and mode of invasion, although its success rate was low in stage
      III, IV (stage classification), grade I (tumor differentiation), grade 3 and 4C
      (mode of invasion).

PMID- 9179608
TI  - Establishment of a reproducible transplantable sarcoma in a rat.
AB  - BACKGROUND: Animal models are valuable tools in cancer research. Mice are the
      most commonly used animals but for surgical procedures, such as bowel anastomosis
      and organ perfusions, larger animals (e.g. rats) are preferable. Unfortunately,
      rat cell-lines are scarce and rat strains are ample, so that adaptation of a cell
      line to the specific strain used in individual laboratories is difficult. In this
      study we present a simple and reproducible model of rat carcinogenesis. MATERIAL
      AND METHODS: Carcinogenesis was induced by 7,12 dimethylbenzantracene dissolved
      in wax and paraffin at 60 degrees C. For matrix production, we used HTR polymers.
      The resulting particles were implanted subcutaneously (SC). RESULTS: Tumors
      occurred in all rats. The resulting tumors, designated GF, were locally invasive
      with low metastatic potential. In vitro doubling time was 7.5 hours. Injection of
      5 x 10(6) cells or transplantation of a tumor fragment resulted in a visible
      tumor within six weeks. The histologic picture and immunohistochemical pattern
      were consistent with pleomorphic soft tissue sarcoma of myogenic origin.
      CONCLUSIONS: This method will enable an individual laboratory to create and
      maintain a sarcoma cell line that will effectively grow in its own rats.

PMID- 9179609
TI  - Interferons alpha, beta and gamma induce different patterns of gene expression in
      cultured human epidermal keratinocytes.
AB  - Differences in the effects on confluent epidermal keratinocytes of treatment with
      interferons (IFNs) alpha, beta, and gamma were observed in their modulation of
      the mRNA levels of representative structural and functional cellular proteins.
      Comparisons of the responses in culture media with varying cellular maturation
      potential indicated the dependence of the modulation on the stage of
      differentiation. Differentiation was correlated with upregulation of all the
      genes by interferon gamma, but this effect was not seen with the other
      interferons. Even though IFNs alpha and beta share the same cell surface
      receptor, their effects on gene expression were clearly distinguishable and
      varied with the culture medium. These findings might have relevance in the
      treatment of skin lesions with varying degrees of differentiation.

PMID- 9179610
TI  - Antitumor activity of novel purine acyclic nucleotide analogs PMEA and PMEDAP.
AB  - PMEDAP and/or PMEA treatment of SD rat lymphomas significantly prolonged the mean
      survival time of tumor-bearing animals. Dose-dependent genotoxicity of both
      PMEDAP and PMEA was not observed in in vitro tests on stabilized diploid MRC-5
      cell line. The mitotic activity of MRC-5 cells was completely inhibited after 48
      hours exposure in culture medium containing PMEDAP (10 micrograms/ml), or PMEA
      (25 micrograms/ml), respectively. Significant concentration dependent inhibition
      of cell proliferation caused by PMEDAP and/or PMEA was also observed in murine
      splenocytes. The analogs specifically inhibit proliferation of mitogen-activated
      T-lymphocytes. Modulation of subpopulations of peripheral blood cells under in
      vivo conditions was found in inbred SD animals. Intraperitoneal administration of
      PMEDAP to young healthy SD animals induced the decrease of the CD4+/CD8+ value
      from 1.3-1.6 to 0.72 while i.p. application of PMEA caused a decrease of the same
      ratio to 0.62.

PMID- 9179611
TI  - Immunophenotypic characterization of canine lymphoproliferative disorders.
AB  - One hundred ninety six dogs with spontaneously occurring lymphoproliferative
      disorders were immunophenotyped. Dogs with lymphoma (175) were determined to be
      derived from B-cells in 134/175 (76%), T-cells in 38/175 (22%) and 3/175 (2%)
      were null cells (non-reactive with any canine-specific lymphocyte antibody). Dogs
      with T-cell lymphomas were at significantly higher risk of relapse and early
      death compared with B-cell lineage lymphoma following therapy (52 vs. 160 days; p
      < 0.001 and 153 vs. 330 days; p < 0.001, respectively). Hypercalcemia was
      associated only with CD4+ lymphomas. A nonimmunoglobulin B-cell marker (B5),
      expressed in 95% of nonneoplastic lymphocytes, was expressed at a reduced level
      in 63% (64/104) of dogs with B-cell lymphoma. Dogs with lymphoma in which the B5
      antigen was expressed below normal levels experienced shorter progression free
      survival (125 vs. 202 days; p < 0.05) and overall survival times (203 vs. 385
      days; p < 0.05) than dogs with B-cell lymphoma in which the B5 antigen was
      expressed normally. Chronic lymphocytic leukemia in dogs was primarily associated
      with a CD8+ phenotype (8/12) and acute lymphoblastic leukemia was determined to
      be of either null cell (4/9) or T-cell (3/9) phenotype. Although canine and human
      non-Hodgkin's lymphoma are phenotypically similar, canine leukemia is
      phenotypically distinct from human leukemia. The development of canine-specific
      probes has facilitated a priori assessment of treatment outcome in dogs with
      lymphoma and may in the future contribute to the comparative understanding of
      leukemo- and lymphoma-genesis in these species.

PMID- 9179612
TI  - The effect of ulinastatin on cutaneous microcirculation during inhalation of 100%
      oxygen in a rabbit ear chamber.
AB  - This study aims to investigate the effects of ulinastatin, a human urinary
      trypsin inhibitor, on the cutaneous microcirculation during inhalation of 100%
      oxygen in the rabbit. Twenty-one rabbits having a rabbit ear chamber (REC), were
      divided into 2 groups: 11 rabbits without ulinastain treatment (Group C) and 10
      rabbits with ulinastatin (Group U). After air inhalation, the inspired gas was
      changed to 100% oxygen. In Group U, 50,000 units of ulinastatin were administered
      before changing the concentration of inspired gas. The results suggests that
      ulinastatin may be useful for maintaining the cutaneous microcirculation during
      inhalation of 100% oxygen.

PMID- 9179613
TI  - Specific expression of HSP27 in human tumor cell lines in vitro.
AB  - The cells of all organisms respond to environmental stress by synthesizing a
      specific group of proteins called heat shock proteins (HSPs). While the
      protective role of HSPs has been observed against cellular stress, recent reports
      have suggested a number of functions of HSPs in various cellular processes in
      normal and pathological conditions. HSP27 is an important low molecular weight
      HSP (Mr: 27,000) found in human cells. HSP27 appears to be involved in
      intracellular signaling and drug resistance in addition to thermotolerance. In
      human breast tumors, a striking association between HSP27 overexpression and a
      shorter disease-free survival period was reported. In this paper, we evaluated
      the expression levels of HSP27 in the cell lines of human breast and other
      tumors. Western blotting of HSP27 has shown the correlation of HSP27 expression
      and metastasis and tumorigenicity of mammary and prostate tumors. Thus the
      biological significance of HSP27 in aggressive mammary and prostate tumors was
      indicated. HSP27 is suggested to be a prognostic marker for the malignancy of
      mammary and prostate tumors.

PMID- 9179614
TI  - In vivo effect of pachymatismin, a new marine glycoprotein, on a human non-small
      cell lung carcinoma.
AB  - Pachymatismin is a novel glycoprotein extracted from a marine sponge, which has
      an antiproliferative effect in vitro on cells from a human non-small-cell
      bronchopulmonary carcinoma (NSCLC-N6). The drug blocks irreversibly the cells in
      the G0/G1 phase of the cell cycle. Here, we investigate the antitumor activity of
      pachymatismin against this cell line. Tumor growth was studied after three weeks
      treatment of nude mice by different doses of pachymatismin. A significant
      decrease in tumor growth was observed.

PMID- 9179615
TI  - Primary human and rat hepatocytes in genotoxicity assessment.
AB  - Primary cultures of human hepatocytes obtained from liver fragments discarded
      during prescribed surgery represent a reliable experimental model that provides
      direct information on the genotoxic effects caused by parent chemicals and their
      reactive metabolites. A comparison between data so far obtained with the DNA
      repair induction (UDS) test in human and rat liver cells is presented. Fourteen
      of the 44 compounds tested were inactive in both species; the man/rat ratio of
      the 30 active compounds ranged from 0.21 to 3.14. Chloramphenicol induced UDS
      only in human hepatocytes, while cimetidine, tripelennamine and four n-alkanals
      caused DNA repair only in rat cells. Three synthetic progestins induced UDS in
      female, but not in male rats, while they were positive in human cells of donors
      of both genders. Primary human hepatocytes would seem to be an important model in
      the study of differences in species sensitivity to xenobiotics.

PMID- 9179616
TI  - Antibacterial immune response in Astacus leptodactylus (Crustacea, Decapoda).
AB  - Antibacterial substances (ABS) in the hemolymph of Astacus leptodactylus were
      studied by agar-plate lysis and inhibition tests. The results demonstrate ABS
      against Gram-positive and Gram-negative bacteria. ABS against Gram-positive
      bacteria were identified as a lysozyme with a molecular weight of 14 kDa, heat
      resistance (< 50 degrees C) and lability to freezing. ABS against Gram-negative
      bacteria lost 50% of their activity at 50 degrees C and completely at 70 degrees
      C but were stable to freezing. Both ABS are inducible; they are produced and
      stored in the granular and semigranular hemocytes. Lysozyme is found in treated
      and untreated animals, ABS against Gram-negative bacteria only after induction.

PMID- 9179617
TI  - A novel thromboxane synthetase inhibitor, DP-1904, inhibits human blood
      eosinophil degranulation.
AB  - Eosinophils have been recognized to be associated with various immune responses
      and disease processes including bronchial asthma. Eosinophils release a number of
      cytotoxic and neurotoxic mediators. However, the factors regulating such release
      and the underlying mechanisms are unclear. In this study, we investigated the
      effect of a selective and potent thromboxane synthase inhibitor, DP-1904, on the
      release of eosinophil cationic protein (ECP) in platelet activating factor (PAF)
      and IgG-stimulated human blood eosinophils. PAF (1 microM) and IgG both released
      ECP which constituted about 25-30% of the total ECP content. The control protein,
      ovalbumin, did not release any ECP over the basal values. DP-1904 in two
      different concentrations, 10 microM and 100 microM, significantly attenuated the
      release of ECP in response to PAF or IgG. The mean percent inhibition by 10
      microM DP-1904 was 49 +/- 10 and 31 +/- 2 against PAF and IgG-induced ECP
      release, respectively. However, at 100 microM DP-1904 the percent inhibition was
      76 +/- 14 and 67 +/- 2, respectively. These data suggest that TXA2 is an
      important mediator in the regulation of eosinophil degranulation, and DP-1904
      thus might prove beneficial in the treatment of bronchial asthma.

PMID- 9179618
TI  - Neutralization of G-CSF inhibits ILK-induced heterophil influx: granulocyte
      colony stimulating factor mediates the Salmonella enteritidis-immune lymphokine
      potentiation of the acute avian inflammatory response.
AB  - Hematopoietic colony stimulating factors (CSF) regulate the growth and
      development of phagocytic cell progenitors and also augment functional activation
      of phagocytes. Granulocyte-CSF (G-CSF) is the CSF that acts specifically upon
      granulocyte progenitor cells and mature granulocytes. We have shown that
      lymphokines (ILK) from T cells of birds immunized against Salmonella enteritidis
      (SE) induce a granulocytic (PMN) inflammatory response in chicks challenged with
      SE. This inflammatory response was characterized by: (a) a dramatic emigration of
      granulocytic cells from the bone marrow into the peripheral blood, (b) an
      enhancement of the biological functions of the circulating PMNs, and (c) a
      directed influx of these activated PMNs to the site of bacterial invasion. In the
      current study, we determined the presence of G-CSF in ILK by Western blot
      analysis using a goat polyclonal antihuman G-CSF antibody (Ab). Using this Ab, we
      then evaluated the role of G-CSF in the ILK-induced protective inflammatory
      response in chickens against SE. Pretreatment of ILK with the Ab totally
      abolished the colony-stimulating activity of the ILK. Furthermore, Ab treatment
      of ILK resulted in: (a) an elimination of the ILK-induced peripheral blood
      heterophilia with a dramatic inhibition of ILK-mediated protection against SE
      organ invasion and (b) an elimination of accumulation of inflammatory PMNs in the
      peritoneum with subsequent decrease in the survival rate of chicks challenged
      i.p. with SE. Taken together these studies demonstrate for the first time the
      contribution of G-CSF to avian PMN activation and the immunoprophylaxis of SE
      infection by ILK in neonatal chickens.

PMID- 9179619
TI  - Tissue plasminogen activator (tPA) inhibits human neutrophil superoxide anion
      production in vitro.
AB  - Because neutrophils contribute to reperfusion injury associated with acute
      myocardial infarction (MI), and because tissue plasminogen activator (tPA) is
      often used in the management of MI, we evaluated the effect of tPA on superoxide
      (O2.-) production by human neutrophils in vitro. We found that adding increasing
      amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced O2.-
      generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro.
      Furthermore, adding tPA that had been previously treated with the protease
      inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased
      neutrophil O2.- generation in vitro (P < 0.05). In contrast, adding L-arginine, a
      component of the tPA preparation and a precursor of nitric oxide (NO), did not
      inhibit PMA-induced neutrophil O2.- production. Also, adding increasing
      concentrations of tPA did not reduce (P > 0.05) the concentrations of O2.-
      produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces
      neutrophil O2.- generation by a mechanism that is not related to L-arginine, is
      not dependent on tPA proteolytic activity, and is not a function of direct
      scavenging. This property may account for some of the effectiveness of tPA in the
      treatment of MI and/or make tPA valuable for treating acute respiratory distress
      syndrome (ARDS) or other inflammatory disorders involving neutrophil O2.-
      production.

PMID- 9179621
TI  - Arteriolar dilation to endotoxin is increased in copper-deficient rats.
AB  - We have previously reported that there is an altered response to mast cell
      mediated inflammation in copper-deficient rats. In the current study we
      determined the microvascular reactivity to inflammatory stimuli with
      lipopolysacccharide (LPS) during dietary copper restriction. Male Sprague-Dawley
      rats were fed purified diets which were either copper-adequate (CuA, 6 micrograms
      Cu/g) or copper-deficient (CuD, 0.4 micrograms Cu/g) for 4 weeks. Rats were
      anesthetized and the cremaster muscle was prepared for in vivo television
      microscopy. Arteriolar diameters were measured and then 2.5 mg/kg LPS was
      injected i.p. In separate groups, animals were pretreated with the NO-synthase
      inhibitor L-NAME (2 x 10(-4) M), the cyclooxygenase inhibitor ibuprofen (9.6 x
      10(-5) M) or the histamine receptor antagonist diphenhydramine (DPH, 10(-6) M).
      LPS caused arteriolar dilation in both dietary groups with the response being
      significantly greater in the CuD group. Ibuprofen and DPH but not L-NAME, each
      significantly reduced but did not block the dilation in the CuD group. Ibuprofen
      and DPH together blocked the dilation. These results suggest that dietary copper
      deficiency increases arteriolar dilation to LPS. The mechanism appears to involve
      a greater response to arachidonic acid metabolites and histamine but not NO.

PMID- 9179620
TI  - An experimental study of the neurogenic and the immunological contribution to
      "tennis elbow" in rats.
AB  - In the present study the content of substance P (SP)-, neurokinin A (NKA)-,
      calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like
      immunoreactivity (-LI) was measured in rats cerebrospinal fluid (CSF), plasma and
      perfusates (PF) from both elbow enthesis during acute inflammation. Either
      substance P, SP, (10-5 M, 0.01 ml) or human recombinant interleukin-1 alpha (hrIl
      1 alpha, 0.01 ml) were injected into the right enthesis of the extensor carpi
      radialis brevis (ECRB). The left ECRB and both ECRBs of control rats, were
      injected with 0.01 ml saline. Samples of CSF, plasma and PF from both ECRBs were
      obtained at 2, 6, and 24 h following injection and neuropeptide-LI was analysed
      by specific radioimmunoassays. Neuropeptide-LI was compared with control values
      and between the treated groups. In both treated groups NKA- and CGRP-LI was
      increased in CSF and NKA-LI decreased in plasma, while CGRP- and NPY-LI were
      raised to a similarly significant degree in the enthesis of the ECRB. SP-LI was
      increased in ECRB PF in comparison with controls and NKA-LI levels were higher in
      the hrIl-1 alpha group both in comparison with controls and between treated
      groups. In summary an unilateral injection of either SP or hrIl-1 alpha into the
      enthesis of the ECRB of the rat showed a similar influence at 2, 6, and 24 h
      following injection. The most pronounced changes in neuropeptide-LI occurred in
      the ECRB PF of both treated groups.

PMID- 9179622
TI  - Mast cell adenosine induced calcium mobilization via Gi3 and Gq proteins.
AB  - Adenosine is an important mediator of mast cell secretory responses. Adenosine
      appears to act through one or more adenosine receptor subtypes to activate
      several signal transduction pathways; however, the specific mechanisms involved
      are not clearly defined. We studied the pathways involved in adenosine receptor
      mediated calcium fluxes in RBL-2H3 cells, a mucosal mast cell-like line. The role
      of endogenous heterotrimeric G proteins in adenosine mediated calcium
      mobilization was investigated by microinjection of inhibitory antibodies that
      block specific G protein subtype function. The calcium transients associated with
      adenosine and antigen stimulation were compared in noninjected cells and cells
      that were microinjected with affinity purified neutralizing antibodies to the
      alpha subunits of Gi3, Gq, or Gs. The percentage of cells responding to adenosine
      was decreased in the presence of antibodies to Gi3 and Gq, but not Gs. Pertussis
      toxin decreased the percentage of cells responding to adenosine, but not antigen.
      These studies demonstrated a functional requirement for the pertussis toxin
      sensitive Gi3 protein and the pertussis toxin insensitive Gq protein in adenosine
      mediated calcium mobilization in mast cells.

PMID- 9179623
TI  - Alpha-1-acid (AAG, orosomucoid) glycoprotein: interaction with bacterial
      lipopolysaccharide and protection from sepsis.
AB  - In the acute phase response to a variety of insults a rise in the levels of the
      acute phase proteins, including elevations of serum alpha 1 acid glycoprotein
      (AAG) occurs. The physiological role of AAG is unknown, however, the time course
      of AAG production in the acute phase response together with its strong affinity
      for basic compounds suggests that AAG may function as an immune modulator to bind
      both exogenous and endogenous inflammatory mediators. Using E. coli
      lipopolysaccharide (LPS), an initiator of the acute inflammatory response
      associated with septic shock, we demonstrate that AAG-LPS complexes can activate
      mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to
      protect against meningococcal endotoxin. To pursue the mechanism of AAG action we
      demonstrated that AAG interacts directly with LPS using dynamic light scattering
      particle sizing and particle mobility. We also determined the enthalpy of
      interaction of AAG and LPS and showed that AAG leads to agglutination of LPS
      impregnated rabbit red blood cells. These studies suggest that AAG may function
      as an immune-modulator in the acute phase response, possibly by counter
      regulating the activity of macrophage pro-inflammatory cytokines.

PMID- 9179624
TI  - Surfactant prevents quartz induced down-regulation of complement receptor 1 in
      human granulocytes.
AB  - Quartz is known to induce an inflammatory response in the alveolar space by
      recruitment of different effector cells. We investigated the interaction between
      granulocytes and quartz with respect to expression of complement receptor type 1
      (CR1) and CR3, with and without the presence of surfactant. Granulocytes from
      hemolyzed blood were stimulated by N-formyl-methionyl-leucyl-phenylalanine
      (fMLP), which mobilize the intracellular pool of CR1 to the surface, and the mean
      fluorescence intensity (MFI) measured by cytofluorometry was 47.4 (46-63.6)
      (median; interquartile range). Quartz exposure reduced the CR1 expression to 23.2
      (22.8-30.6) MFI units (P < 0.01), a porcine surfactant preparation added during
      quartz exposure abolished the down-regulation completely, 47.7 (43.2-62.3) MFI
      units (P < 0.001). Similar results were obtained after preincubation of the cells
      with surfactant followed by quartz exposure. No significant influence on CR1
      expression was found by a synthetic lipid mixture, nor was the CR3 expression
      affected. In conclusion, this study demonstrates that the presence of surfactant
      inhibits quartz induced down-regulation of CR1 on activated granulocytes.

PMID- 9179625
TI  - The effect of sodium aurothiomalate on stimulated and non-stimulated migration by
      human neutrophils: the role of cyclic GMP.
AB  - Preincubation of human neutrophils with aurothiomalate had little effect on
      random migration or chemotactic migration towards the chemotactic peptide fMLP.
      However, a strong enhancement of migration was observed when aurothiomalate was
      present in a concentration gradient; the effect of the drug was chemotactic
      rather than chemokinetic. Thiomalate also caused a chemotactic enhancement of
      migration but here a tenfold higher concentration of the drug was required as
      compared with aurothiomalate. Aurothiomalate caused an increase of cellular cGMP
      level, and inhibitors of guanylate cyclase inhibited the activating effect of
      aurothiomalate. Three specific antagonists of cGMP-dependent kinase (G-kinase)
      strongly inhibited aurothiomalate-induced migration of electroporated
      neutrophils. The results suggest that stimulation of migration by aurothiomalate
      is mediated by cGMP and a G-kinase. Monoclonal anti-IL-8 inhibited aurothiomalate
      induced stimulation of migration. Though no increased release of IL-8 could be
      established upon exposure of neutrophils to aurothiomalate, it seems conceivable
      that the stimulating effect of aurothiomalate is mediated by IL-8.

PMID- 9179626
TI  - Upregulation of lymphoid and renal interferon-gamma mRNA in autoimmune MRL
      Fas(lpr) mice with lupus nephritis.
AB  - MRL-Fas(lpr) mice develop an aggressive form of autoimmunity, characterized by
      immune complex-mediated glomerulonephritis and massive expansion of lymphoid
      tissues. Increased MHC class II expression by macrophages and renal parenchymal
      cells is a prominent feature of MRL-Fas(lpr) mice. Since interferon-gamma (IFN
      gamma) is the major and the most potent inducer of MHC class II molecules it
      could play a pathogenic role in the disease process in MRL-Fas(lpr). We have
      analyzed IFN-gamma expression in normal and nephritic MRL-Fas(lpr) mice by
      examining renal and lymphoid IFN-gamma-specific mRNA production, using reverse
      transcription-polymerase chain reaction (RT-PCR) and Northern blotting. We detect
      abundant IFN-gamma mRNA expression in the kidney of nephritic MRL-Fas(lpr) by RT
      PCR, whereas normal mice display absent or only very weak expression of this
      cytokine. By RT-PCR, IFN-gamma mRNA is detectable in normal spleen, but is
      overexpressed in the enlarged spleen and lymph nodes of MRL-Fas(lpr). Northern
      blotting using total RNA from tissues confirms abundant IFN-gamma expression in
      spleen and lymph node of MRL-Fas(lpr). We conclude that enhanced renal IFN-gamma
      mRNA expression is a prominent feature of MRL-Fas(lpr) lupus nephritis. Increased
      IFN-gamma produced by infiltrating T cells could lead to increased MHC class II
      expression by renal parenchymal cells, thereby promoting the nephritic process by
      augmentation of antigen presentation in the kidney of autoimmune MRL-Fas(lpr).

PMID- 9179628
TI  - Psychopharmacogenetic basis of medication-induced movement disorders.
AB  - In light of the emerging evidence for genetic vulnerability to adverse drug
      reactions, this article attempts to elucidate the natural history of medication
      induced movement disorders from a psychopharmacogenetic perspective. Studies of
      the risk factors, neurobiology, and pharmacogenetics are reviewed concurrently.
      The relevant variables associated with 10 genetically mediated movement disorders
      are tabulated and compared with those of medication-induced movement disorders
      without a clear-cut genetic basis. As a result of this integrated analysis, it is
      evident that there is an intimate genetic and pathophysiological link between
      neuropsychiatric movement disorders of diverse origins. The emergence of drug
      induced movement disorders seems to reflect a spectrum of basal ganglia
      derangement attributable to genetic predisposition; psychotropic medications only
      augment the genetic vulnerability to clinical phenotypes. It is proposed that a
      multidimensional analysis of the interacting variables is essential for
      understanding the natural history of these conditions, and that the scope of
      psychopharmacology should be broadened to include psychopharmacogenetics for
      improving therapeutic objectivity and prevention research.

PMID- 9179629
TI  - A review of the psychomotor effects of paroxetine.
AB  - All 10 placebo-controlled studies of the psychomotor effects of paroxetine are
      reviewed. The total number of subjects is 195. The majority of studies show
      little or no effect of paroxetine on psychomotor function. No adverse effects are
      apparent at the dose of 20 mg/day, although minor impairments can be identified
      at 40 mg/day. An overview of the data indicates that at the standard therapeutic
      dose of 20 mg/day, paroxetine has no psychomotor or behavioural toxicity.

PMID- 9179627
TI  - Cytokine and nitric oxide production in the acute phase of bacterial cell wall
      induced arthritis.
AB  - We have investigated the temporal relationship among proinflammatory cytokine
      expression, nitric oxide (NO) production and joint inflammation in the acute
      phase of bacterial cell wall-derived peptidoglycan polysaccharide (PG/PS)-induced
      arthritis. Acute joint inflammation was induced in female LEW/N rats by a single
      intraperitoneal injection of PG/PS. Arthritis index and paw volume were
      quantified and joint histopathology was evaluated during acute joint inflammation
      (0-10 days). Tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6
      (IL-6) were determined by bioassay whereas nitric oxide (NO) was quantified by
      measuring serum nitrate/nitrite levels via the Griess procedure. We found that
      serum levels of TNF and serum IL-1 preceded the increase in IL-6 and NO
      production. Furthermore, the production of these proinflammatory cytokines and NO
      preceded bone erosion and osteoclast activity. Erosion of subchondral bone
      preceded pannus formation and cellular synovitis in the acute phase of PG/PS
      induced arthritis. The temporal expression of TNF, IL-1, IL-6 and NO suggest a
      cascade of inflammatory mediators in which monocytes and macrophages respond to
      PG/PS with enhanced synthesis of TNF and IL-1, which may in turn promote the
      synthesis of IL-6 and NO. We postulate that one or more of these inflammatory
      events are responsible for initiating the subchondral bone erosion observed in
      acute joint inflammation.

PMID- 9179630
TI  - Depression in the community: the first pan-European study DEPRES (Depression
      Research in European Society).
AB  - DEPRESS (Depression Research in European Society) is the first large pan-European
      survey of depression in the community. A total of 13359 of the 78463 adults who
      participated in screening interviews across six countries were identified as
      suffering from depression, a 6-month prevalence of 17%. Major depression
      accounted for 6.9% of the cases of depression and minor depression for 1.8%.
      Depressed subjects in both these categories perceived that their working or
      social lives were substantially impaired by depressive symptoms. The remaining
      8.3% of depressed subjects considered that their functional impairment was not
      substantial. A significant proportion of sufferers from depression (43%) failed
      to seek treatment for their depressive symptoms. Of those who did seek help
      (57%), most consulted a primary care physician, the frequency of consultation
      increasing with the severity of depression. Sufferers from major depression
      imposed the greatest demand on healthcare resources, making almost three times as
      many visits to their GP or family doctor as non-sufferers (4.4 vs 1.5 visits over
      6 months). More than two-thirds of depressed subjects (69%) were not prescribed
      any treatment and when drug therapy was prescribed (31%), only 25% of these
      subjects were given antidepressant drugs. The number of days of work lost due to
      illness increased with the severity of depression. Major depression had most
      impact on productive work, with sufferers losing four times as many working days
      over 6 months as non-sufferers. The results of the DEPRES survey confirm the high
      prevalence of depression in the community and the burden imposed on the
      individual sufferer in terms of impaired quality of life and on society in terms
      of healthcare utilization and lost productivity.

PMID- 9179631
TI  - Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic
      dimension in schizophrenia.
AB  - There is increasing evidence suggesting that symptoms of depression and anxiety
      may also be associated with serotonergic dysfunction in schizophrenic patients.
      The effect of the adjuvant selective serotonin reuptake inhibitor citalopram was
      assessed regarding the symptom dimensions of schizophrenia measured with the
      Positive and Negative Syndrome Scale (PANSS) and with the Hamilton Rating Scale
      for Depression (HRSD). Citalopram alleviated symptoms of the depression/anxiety
      dimension of the PANSS, but not the symptoms of the four other PANSS domains or
      depressive symptoms measured with the HRSD. The results support the hypothesis of
      a serotonergic dimension in schizophrenia.

PMID- 9179632
TI  - Reflux oesophagitis and clozapine.
AB  - In a series of thirty-six patients treated with clozapine we report four cases
      who developed upper gastrointestinal symptoms suggestive of reflux oesophagitis
      within 6 weeks of starting this drug. Subsequent endoscopic examination revealed
      moderately severe erosive oesophagitis in three of them. Of these one had
      received treatment for a peptic ulcer in the past but the other two had no
      previous history of any upper gastrointestinal disorder. The pharmacology of
      clozapine in relation to gastro-oesophageal reflux is discussed.

PMID- 9179633
TI  - The eight-item treatment-outcome post-traumatic stress disorder scale: a brief
      measure to assess treatment outcome in post-traumatic stress disorder.
AB  - This preliminary report describes a new brief interview based assessment of post
      traumatic stress disorder using an 8-item treatment-outcome post-traumatic stress
      disorder scale (TOP-8). The TOP-8 was developed from a larger post-traumatic
      stress disorder evaluation scale based on items which occurred frequently in the
      population and which responded substantially to treatment across time. The 8
      resultant items were drawn from all three symptom clusters for post-traumatic
      stress disorder, and showed an improved ability to detect drug versus placebo
      differences in comparison with the original scale. The eight-item treatment
      outcome post-traumatic stress disorder scale also correlated significantly with a
      self-rated measure of post-traumatic stress disorder and distinguished at a
      highly significant level between responders and non-responders on an
      independently judged Clinical Global Impressions measure. The results of this
      study are discussed and future directions suggested.

PMID- 9179634
TI  - An open study of the efficacy and adverse effects of moclobemide in patients with
      the chronic fatigue syndrome.
AB  - There is a strong association between the chronic fatigue syndrome and both
      depressive illness and sleep disturbance, but the efficacy of antidepressants is
      uncertain. We studied the efficacy and adverse effects of moclobemide in patients
      with chronic fatigue syndrome, stratifying the sample both by co-morbid major
      depressive illness and by sleep disturbance. Forty-nine patients with chronic
      fatigue syndrome were recruited. Patients were given moclobemide up to 600 mg a
      day for 6 weeks. Four (8%) patients dropped out, three because of adverse
      effects. Adverse effects wee otherwise mild and transient. On analysing the whole
      sample, there were significant but small reductions in fatigue, depression,
      anxiety and somatic amplification, as well as a modest overall improvement. The
      greatest improvement occurred in those individuals who had a co-morbid major
      depressive illness, with seven out of 14 (50%) of such individuals rating
      themselves as "much better" by 6 weeks, compared to six out of 31 (19%) of those
      who were not depressed (31% difference, 95% CI 1-60%, P = 0.04). Sleep
      disturbance had no effect on outcome. Moclobemide may be indicated in patients
      with chronic fatigue syndrome and a co-morbid major depressive disorder. A
      randomized, placebo-controlled trial is needed to confirm this. These results do
      not support moclobemide as an effective treatment of chronic fatigue syndrome in
      the absence of a major depressive disorder.

PMID- 9179635
TI  - Mianserin and restless legs.
AB  - Six cases of restless legs syndrome in association to mianserin are presented.
      Similarities and differences to previously reported cases are described. Some
      theoretical and methodological topics on restless legs syndrome in relation to
      drug-induced akathisia are discussed.

PMID- 9179636
TI  - Antagonism of selective serotonin reuptake inhibitor-induced nausea by
      mirtazapine.

PMID- 9179637
TI  - Combined serotonin syndrome and hyponatraemia caused by a citalopram-buspirone
      interaction.

PMID- 9179639
TI  - Differentiation of classical and novel antipsychotics using animal models.
AB  - The criteria that have been used to differentiate classical and atypical
      antipsychotics include measures of neurological and cognitive side effects and
      therapeutic effects. Novel antipsychotic compounds with few or no extrapyramidal
      syndromes (EPS) can be differentiated from classical neuroleptics by a number of
      animal models for limbic selectivity and dose-response separation between
      behavioral and pharmacological parameters analogous to EPS and antipsychotic
      effects. The results obtained using these models seem to be concordant with
      clinical findings. Moreover, animal models expand our understanding of the
      pharmacological mechanisms responsible for EPS and for the therapeutic effects of
      antipsychotics, and they allow an examination of the possible effects of new
      compounds on cognition. Here we review a number of key reports on the
      differentiation of classical and novel antipsychotics using animal models.

PMID- 9179638
TI  - D2 occupancy, extrapyramidal side effects and antipsychotic drug treatment: a
      pilot study with sertindole in healthy subjects.
AB  - Acute extrapyramidal syndromes (EPS) are frequently recorded during treatment
      with classical neuroleptic drugs. In patients with EPS a consistent finding is
      high central D2-receptor occupancy (> 80%) as demonstrated with positron emission
      tomography (PET). The exception is clozapine, an atypical antipsychotic which has
      low EPS liability and also induces a low D2 occupancy (20-67%). We have proposed
      that the PET demonstration of low D2 occupancy at antipsychotic dose levels can
      be viewed as a strategy to confirm atypicality. There have been strong incentives
      in recent years to discover new drugs which do not induce EPS, but so far no drug
      has been shown unequivocally to have the low D2 occupancy and EPS liability
      reported for clozapine. Sertindole is a new antipsychotic drug which has shown a
      low incidence of acute EPS in clinical studies. In the present study PET was used
      to measure central D2-dopamine receptor binding in the basal ganglia at baseline
      and 6 h after oral administration of 4 mg sertindole to two healthy males. D2
      dopamine receptor occupancy was 15% in one subject and 6% in the other. The low
      occupancy level demonstrated at 4 mg indicates the need for a PET study in
      patients at the suggested clinical dose level of 12-24 mg a day. In particular,
      it is important to determine whether sertindole induces antipsychotic effects at
      a D2 occupancy level which is lower that found in patients treated with classical
      antipsychotics.

PMID- 9179640
TI  - Will the new antipsychotics bring hope of reducing the risk of developing
      extrapyramidal syndromes and tardive dyskinesia?
AB  - Treatment of psychotic symptoms with traditional neuroleptics has been
      complicated by acute extrapyramidal syndromes (EPS) and late occurring tardive
      dyskinesia. These widely prevalent disorders have both motor and mental
      components which impose additional impairments on patients who are already
      substantially limited by their psychoses. Research activities with new drugs
      involve multiple neurotransmitters and different receptor subtypes. These new
      approaches have produced an increasingly desirable group of antipsychotic agents
      with a low EPS profile. The initial advances in low EPS with clozapine and
      risperidone are being followed up with further gains using agents such as
      sertindole, olanzapine and seroquel. The advent of these new agents seems likely
      to fulfill the promise that it is possible to have antipsychotic agents with a
      low EPS liability, and possibly a low risk of tardive dyskenesia.

PMID- 9179641
TI  - Sertindole in the treatment of psychosis in schizophrenia: efficacy and safety.
AB  - Evidence from clinical trials supports the claim that sertindole is a potent
      antipsychotic drug at a dose of 12-24 mg/day. Its action against positive
      symptoms is as potent as that of the traditional antipsychotic haloperidol. Its
      action against negative symptoms is significantly different from that of placebo
      and quantitatively larger than that of haloperidol. Its most distinctive
      characteristic is a reduction in motor side effects over a whole range of
      comparable drug and comparator doses. More work is needed to determine whether
      sertindole's actions against negative symptoms influence the primary or the
      secondary negative system. There are insufficient data at present to compare
      sertindole with the highly efficacious drug clozapine or the other new
      antipsychotic olanzapine.

PMID- 9179642
TI  - Towards the improvement of compliance: the significance of psycho-education and
      new antipsychotic drugs.
AB  - Effective pharmacological, psychosocial and other kinds of treatment are now
      available for schizophrenia. Often, however, neither acute nor long-term
      treatment can be properly applied because of insufficient compliance by both
      patients and doctors. Patient non-compliance is as high as 50% under outpatient
      conditions; potential reasons may be either illness-related (e.g. lack of insight
      or idiosyncratic concepts of the illness or its treatment), drug-related (e.g.
      intolerable side-effects) or related to inadequate treatment management (e.g.
      insufficient information or lack of environmental support). Non-compliance by
      doctors is partly due to limited adherence to treatment guidelines. To improve
      both patient and doctor compliance, the use of educational tools for professional
      health-care providers, patients and families should be generally enforced. New
      antipsychotics with a better risk-benefit profile with respect to clinical
      efficacy and side effects will probably help to overcome drug-related non
      compliance.

PMID- 9179643
TI  - What can we achieve by implementing a compliance-improvement program?
AB  - Efforts to improve compliance and facilitate other aspects of relapse-prevention
      strategies can have a profound impact on the lives of millions of people around
      the world as well as conserving precious health-care dollars. Simultaneous
      efforts to educate patients and families on the nature of the disease, its course
      and optimum treatment, together with efforts to educate physicians and other
      health-care professionals on the indications, benefits and risks of long-term
      treatment, are critical for improving the current state of affairs. In addition,
      it is imperative to educate the public at large and particularly those health
      care administrators and public servants who control or influence the allocation
      of the resources needed.

PMID- 9179644
TI  - Progressive multifocal leukoencephalopathy in HIV.
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system caused by infection of oligodendrocytes by JC virus.
      As patients with HIV survive longer with severe immunodeficiency, the incidence
      of PML is rising. Diagnosis is not always easy and the gold standard remains
      histological confirmation of the characteristic lesions of PML which requires a
      brain biopsy. This is considered too invasive by many clinicians and patients
      alike and detection of JC virus DNA in the cerebrospinal fluid (CSF) using
      polymerase chain reaction (PCR) is used as an alternative to biopsy. JC virus
      subtype detection in brain, CSF and blood leukocytes may offer further diagnostic
      and prognostic possibilities. The aetiology, clinical features and diagnostic
      problems of PML are reviewed. At present the outlook for patients with confirmed
      PML is poor and there is currently no effective treatment. However, novel
      approaches to treatment are under investigation and show some promise.

PMID- 9179645
TI  - The ocular complications of HIV and AIDS.

PMID- 9179646
TI  - Comparison of patients refusing with patients accepting unlinked anonymous HIV
      testing in an outpatient STD department in The Netherlands.
AB  - From 1 February 1993 to 1 February 1994 all new patients, known patients with new
      problems, and prostitutes attending the Outpatient Department of Sexually
      Transmitted Diseases (STD) of the University Hospital Rotterdam were asked to
      participate in unlinked anonymous human immunodeficiency virus (HIV) testing and
      to answer some questions. Data from the medical records of 300 patients refusing
      to participate were compared with self-reported data obtained from 2701 people
      accepting, to verify if the HIV seroprevalence among accepters could be
      representative for all STD department visitors. Men refusing were more often of
      foreign origin, had more often had more than one partner during the previous 6
      months, more often attended the STD department for the first time, and more often
      had an STD diagnosed than men accepting. Women refusing were more often of
      foreign origin, had less often had more than one partner during the previous 6
      months, and had more often used drugs intravenously than women accepting. Because
      most findings associated with refusing are also associated with being infected
      with HIV, the HIV seroprevalence among refusers is likely to be higher than among
      accepters. We therefore advise unlinked anonymous HIV testing of all patients
      visiting an STD department.

PMID- 9179647
TI  - STD/AIDS knowledge and risk behaviour among masseuses and bar hostesses in
      Singapore.
AB  - Sex workers are not confined to brothels, they also include a variety of
      individuals who practise part-time in establishments conductive to sexual
      liaisons. We undertook to study the extent of sex work among masseuses and
      nightclub hostesses and the level of AIDS and STD knowledge in these 2 groups.
      The studies were conducted in 1993 and 1996. Altogether 1244 masseuses and 746
      hostesses attended educational sessions at the STD clinic, during which they were
      also surveyed for knowledge on AIDS and STDs, and practices which may put them at
      risk of infection; they were also offered tests for HIV and syphilis. Knowledge
      on AIDS transmission was good, knowledge of other aspects of AIDS and STDs was
      not. Sexual activities resulting from the conduct of their work was practised by
      only a minority of masseuses (13.5%) and hostesses (7.9%). Among those who
      engaged in sexual activities at work, masseuses practised safe sex more commonly
      than hostesses (83.5% vs 27.6%). The prevalence of HIV (0.175% in hostesses, 0%
      in masseuses) and syphilis (0.87% in hostesses and 1.7% in masseuses) was very
      low in both groups.

PMID- 9179648
TI  - Difference of virus populations in HIV carriers in relation to AZT treatment.
AB  - To analyse the appearance of AZT-resistant HIV in HIV carriers after AZT
      treatment and compare the mutations responsible for resistance employing cloned
      HIV DNA derived from provirus and free virions in plasma, serial blood specimens
      were taken before and after AZT treatment. RNA in virions in plasma, proviral DNA
      and RNA from virus isolates by coculture of PBMCs of HIV carriers and healthy
      blood donors were cloned and sequenced. DNA clones were compared for their
      nucleotide sequences responsible for AZT resistance. AZT resistance was acquired
      as early as 2 months after the start of the treatment and follow-up study was
      performed for 16 months of the treatment. Population of DNA clones was different
      according to the origin of the DNA or RNA, which indicated that the provirus
      population in PBMC was different from that in virions in plasma. These data
      demonstrated the possibility of selective activation of provirus or activation of
      provirus in organs other than peripheral blood, although the number of cases was
      small.

PMID- 9179649
TI  - The epidemiology of notified genital Chlamydia trachomatis infection in Victoria,
      Australia: a survey of diagnosing providers.
AB  - Data on 259 notified cases of genital chlamydia infection diagnosed in Victoria
      Australia in January and February 1995 were augmented by call-back. Risk factor
      data was available for 221. Patients were primarily adolescents or young adults
      (median age 23 years); 66% were women. Men were more commonly symptomatic.
      Persons without symptoms were tested as a result of partner notification, sexual
      risk, termination of pregnancy, or because of abnormalities on genital
      examination. Limitations of antigen-based screening tests in low prevalence
      populations were rarely considered. Although antimicrobial treatment usually
      accorded with available guidelines, case management was not well geared to
      reducing the broader issue of risk of this infection in the community. Data
      management systems for handling name-coded data, and systems for recall and
      follow-up of diagnosed patients and their partners were often inadequate. Sexual
      history taking had not generally identified details of sexual partners. Partner
      notification was generally regarded as the patient's responsibility and
      professional help with contact tracing was rarely sought. Control of chlamydia
      will require much greater attention to management issues, particularly contact
      tracing.

PMID- 9179650
TI  - Lack of behavioural risk factors for squamous intraepithelial lesions (SIL) in
      HIV-infected women.
AB  - HIV-infected women have a high prevalence of abnormal Papanicolaou smears and
      cervical intraepithelial neoplasia. A multiparametric analysis of epidemiological
      and behavioural risk factors has been performed in a cohort of 204 HIV-infected
      women in an outpatient clinic with the aim to investigate risk factors associated
      with squamous intraepithelial lesions (SIL) in HIV-seropositive women. The
      prevalence of SIL in the study population was 35.7%. Univariate and multivariate
      analysis of demographic, behavioural and immunological variables only identified
      cigarette smoking > 20/day and CD4+ cell counts < or = 200 x 10(6)/L as risk
      factors significantly associated with SIL in the study population. We found no
      epidemiological/behavioural risk factors specifically associated with SIL in HIV
      infected women as compared with the general population. The results suggest that
      the high prevalence of SIL in HIV disease is related to acquired immune
      deficiency in HIV-seropositive women.

PMID- 9179651
TI  - Severe primary HIV-1 infection among black persons in Barbados.
AB  - Descriptions of primary HIV-1 infection have so far been based on Caucasians
      living in industrialized nations. Due to studies of leptospirosis in the
      predominantly black population of Barbados, serum was available for patients
      admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By
      searching the medical records of 510 adult patients with known HIV-1 infection we
      identified 10 patients who had stored serum from an admission for an acute
      febrile illness that predated or coincided with their first HIV-1-positive test.
      Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in
      the 10th patient. The clinical features of these 10 patients were in keeping with
      previous descriptions of primary HIV-1 infection but differed from leptospirosis
      cases seen at the QEH. One patient died during his seroconversion illness and
      another died 3 months after seroconversion. The findings suggest that severe
      primary HIV-1 infection could be a relatively uncommon occurrence, that the
      condition may be misdiagnosed, and that cases may not occur until the AIDS
      epidemic is established.

PMID- 9179653
TI  - The provision of psychosexual services by genitourinary medicine physicians in
      the United Kingdom.
AB  - A postal questionnaire survey, enquiring about the provision of psychosexual
      services, was sent to each GUM clinic in the UK. Of the 246 questionnaires
      distributed, replies were received from 166 directors responsible for 171 (69.5%)
      clinics. Of the 140 (84%) who supported the provision of a sexual dysfunction
      service, 59 (42%) currently provided such a service. Doctors and psychologists
      were the health care professionals most commonly involved in sexual dysfunction
      services for patients who were referred both internally and from external sources
      such as general practice and diabetic clinics. Patients with a variety of
      dysfunctions were being treated with a broad range of therapies, a reflection
      probably of the multidisciplinary nature of the team providing the service.
      However, it appears that junior doctors are not being trained in this field at
      present.

PMID- 9179654
TI  - Hypercalcaemia in a patient with AIDS and Mycobacterium avium intracellulare
      infection.

PMID- 9179652
TI  - Rise in sexually transmitted diseases during democratization and economic crisis
      in Mongolia.
AB  - In 1990, democratic changes and loss of Soviet economic subsidies led to enormous
      social upheaval in Mongolia. The objective of this study is to map sexually
      transmitted disease (STD) trends in Mongolia from 1983-1995 and review human
      immunodeficiency virus (HIV) surveillance data since 1987. Data for syphilis show
      a decreasing trend from 1983-1993 with a decline in cases from 70 to 18/100,000
      population, followed by a rise in cases to 32/100,000 population in 1995. Data
      suggest a 1.5-3.0 fold higher rate of syphilis for ages 15-24 than for any other
      group. Data for gonorrhoea show an upward trend in the rate of cases, from
      51/100,000 population in 1983 to 142/100,000 in 1995. The majority of cases are
      aged 15-44. Trichomonas rates also show an upward trend in the number of cases,
      from 47/100,000 population in 1983 to 155/100,000 cases in 1995. Like gonorrhoea
      the majority of cases are in the 15-44 year age range. For children aged 0-14,
      the 1983-1993 rate remained below 4.5/100,000; however, in 1994 and 1995 the rate
      increased reaching 53 and 48/100,000 respectively. Since 1987, more than 176,000
      HIV tests have been done with only one confirmed positive result. Rises in STD
      rates coincide with deterioration in STD services and reduced active
      surveillance, suggesting that these data reflect a minimum estimation of the
      problem. Changes in business and social circumstances may have resulted in
      increasing HIV and STD risk behaviour.

PMID- 9179655
TI  - Liposomal amphotericin B and recombinant human granulocyte-macrophage colony
      stimulating factor (rHuGM-CSF) in the treatment of paediatric AIDS-related
      cryptococcosis.

PMID- 9179656
TI  - An audit of the management of pelvic inflammatory disease.

PMID- 9179657
TI  - Genital warts, trichomoniasis and other concurrent STIs in Scotland.

PMID- 9179658
TI  - Testis-determining factor and gonadal dysgenesis.

PMID- 9179660
TI  - Surgical approach to tumor thrombus of renal cell carcinoma at the level between
      hepatic vein and diaphragm.
AB  - BACKGROUND: The curative resection of tumor thrombus of renal cell carcinoma
      often provides a good prognosis, but the best surgical method for resection at
      the level between hepatic vein and diaphragm is still a matter of controversy.
      METHODS: We performed transabdominal surgery without cardio-pulmonary bypass on 4
      patients with tumor thrombus at the level between hepatic vein and diaphragm. The
      surgical procedures were as follows: The right lobe of the liver was separated
      and detached from the retroperitoneum, and then the vena cava was clamped just
      below the diaphragm simultaneous with clamping the porta hepatis. After complete
      circulatory isolation of the vena cava, the tumor thrombus was resected. RESULTS:
      There were no severe complications postoperatively. Two patients died of cancer
      18 and 38 months after surgery, and the other 2 are alive without evidence of
      disease after 62 and 66 months. CONCLUSION: This anatomically rational approach
      is thought to be a good alternative to the pull-through method or cardio
      pulmonary bypass for removing a tumor thrombus at this level.

PMID- 9179659
TI  - Postoperative UFT adjuvant and the risk factors for recurrence in renal cell
      carcinoma: a long-term follow-up study. Kyushu University Urological Oncology
      Group.
AB  - BACKGROUND: Radical nephrectomy is the standard therapy for low-stage renal cell
      carcinoma. However, recurrence sometimes develops even in patients who are
      considered to have undergone a curative resection of the primary tumor. The
      purpose of this study was to evaluate the usefulness of UFT (a 1:4 mixture of
      tegafur and uracil) adjuvant and the risk factors for recurrence in renal cell
      carcinoma. METHODS: A prospective randomized trial was conducted to compare the
      use of long-term oral UFT adjuvant with nonadjuvant therapy after a radical
      nephrectomy for Robson stage I or II renal cell carcinoma. A multivariate
      analysis was also performed to estimate the risk factors for recurrence. RESULTS:
      A total of 71 patients were entered into this study, and 66 were evaluable (33
      for each group). There was no significant difference in patient characteristics
      between the 2 groups. The nonrecurrence rate at 5 years after a radical
      nephrectomy was 80.5% and 77.1% in the UFT adjuvant group and the nonadjuvant
      group, respectively, with a median follow-up of 112.9 months; the difference was
      not significant. The toxicity of UFT was generally mild and tolerable. The tumor
      grade was found to be an important factor influencing recurrence. CONCLUSION: UFT
      cannot be universally recommended as an adjuvant therapy for radical nephrectomy
      in all patients with low-stage renal cell carcinoma.

PMID- 9179661
TI  - Urinary reconstruction using appendix as a urinary and catheterizable conduit in
      12 patients.
AB  - BACKGROUND: The appendix vermiformis can provide an excellent urinary conduit or
      a catheterizable outlet in continent urinary reservoirs in selected cases. We
      report our clinical experience using the appendix in urinary reconstruction in
      adult patients. METHODS: A total of 12 patients underwent urinary reconstruction
      using the appendix. The indications were pelvic malignancies except for 1 patient
      with neurogenic bladder and difficulty in self-catheterization via urethra. The
      appendix was used as a catheterizable conduit in 8 patients, and as a urinary
      conduit in 4 patients. The in situ submucosally embedded method was used in 6
      patients and the Mitrofanoff method was used in 2 patients. Follow-up ranged from
      3 to 41 months (mean, 22). RESULTS: Early complications occurred in 3 patients
      (wound infection, false passage and intestinal anasotomotic leak). Late
      complications occurred in 3 (slight hydronephrosis, ileus, stomal stenosis).
      Emergent colostomy and pouchstomy with resection of the appendix was performed in
      the patient with anastomotic leak. The isoperistaltic Kock nipple valve was
      reconstructed for continence in this case. Prolonged ileus in 1 patient was
      treated by open surgery. Other complications were managed conservatively. End
      results were excellent in 8 patients, good in 3, and poor in 1. CONCLUSIONS: The
      appendix can be used advantageously as an outlet of continent urinary reservoirs
      or for a urinary conduit when the ureter is too short to reach the skin. Complete
      continence and easy catheterization can be obtained, and the appendix
      construction can be used as a urinary conduit instead of the ileal conduit in
      poor risk patients.

PMID- 9179662
TI  - Vitamin B12 deficiency in patients with urinary intestinal diversion.
AB  - BACKGROUND: Because vitamin B12 is absorbed exclusively by the terminal ileum, we
      investigated vitamin B12 deficiency as a potential metabolic complication after
      urinary intestinal diversion. METHODS: We measured serum levels in patients with
      Kock pouches (n = 35); Indiana pouches (n = 27); and ileal conduits (n = 25).
      Serial determinations of serum B12 levels were obtained in 19 patients with kock
      pouches and 14 patients with Indiana pouches. The dual-isotope Schilling test was
      performed in 9 patients with Kock pouches and 6 patients with Indiana pouches.
      RESULTS: No patient had an abnormally low serum B12 level (< 200 pg/mL). Mean (+/
      SD) serum B12 levels in patients with the Kock pouch (506 +/- 202 pg/mL) and the
      Indiana pouch (536 +/- 249 pg/mL) were lower than that in patients with the ileal
      conduit (727 +/- 391 pg/mL). The mean serum B12 level was not significantly
      different between patients with and without preoperative irradiation. Serial
      determinations showed that serum B12 levels in some patients with continent
      urinary reservoirs were persistently near the lower normal limit, or became
      progressively lower. Three of the 9 patients (33%) with Kock pouches and 4 of the
      6 patients (67%) with Indiana pouches were B12 malabsorbers, although no patients
      had megaloblastic anemia or neurologic symptoms. CONCLUSIONS: Some patients with
      continent urinary reservoirs are at risk for vitamin B12 deficiency due to
      malabsorption. Routine evaluation of serum B12 levels is recommended for all
      patients with continent urinary reservoirs, and a Schilling test for those with
      subnormal serum B12 levels.

PMID- 9179663
TI  - Quality of life survey of urinary diversion patients: comparison of continent
      urinary diversion versus ileal conduit.
AB  - BACKGROUND: Continent urinary reservoirs (CUR) have become one of the major
      options for patients requiring urinary diversion to improve their quality of life
      (QOL). To assess whether CUR enhanced postoperative QOL, we surveyed patients
      with CUR and ileal conduit (IC) using a questionnaire sent by mail. PATIENTS AND
      METHODS: The questionnaire consisted of 133 questions that covered physical and
      mental status, social life, sexual habits and symptoms related to urinary
      diversions. A total of 172 questionnaires were sent out, and 137 (80%) patients
      (74 CUR and 63 IC patients) responded. RESULTS: Basic physical conditions were
      similar in the 2 groups, except for sleeping habits. Regarding social life,
      however, the CUR group showed better scores in bathing habits and frequency of
      overnight travel. Parastomal dermatitis was more frequent in the IC group and the
      patients were more hesitant to show their stoma to others. On the other hand,
      about half of the patients in the CUR group complained of troublesomeness in self
      catheterization, especially at night. Overall, 74% and 41% of the patients in the
      CUR and IC group were satisfied with their urinary diversion. When the Kock pouch
      and Indiana pouch were compared, no statistically significant differences were
      found in average capacity, maximum capacity, or frequency of self
      catheterization. CONCLUSIONS: CUR recipients have enhanced QOL regarding the
      stoma, travel and sleeping habits as compared to ileal conduit. However,
      troublesomeness of night time self-catheterization was noted in the CUR group.
      Individualized selection of the type of urinary diversion with informed consent
      is essential.

PMID- 9179664
TI  - Feasibility of urodynamic study (combined cystometry and electromyography of the
      external urethral sphincter) under general anesthesia in children.
AB  - BACKGROUND: To assess the feasibility of urodynamic study under general
      anesthesia (GA) we performed electromyography of the external urethral sphincter
      (EUS-EMG) on 73 children and cystometry (CM) alone on 10 children. METHODS:
      Subjects were divided into 3 groups. Those in groups I and II were suspected of
      having voiding dysfunction with (group I) or without (group II) overt neurospinal
      defects, while those in group III were thought to be functionally normal. EUS-EMG
      was performed under light anesthesia following cystourethroscopy to examine
      structural abnormalities. Atropine sulfate premedication was not used for the
      anesthetic procedure; muscle relaxants were used only for tracheal intubation.
      RESULTS: Voiding was observed in 83% of the patients. Among patients who voided,
      detrusor-external sphincter dyssynergia (DSD) was noted in 7 (38%) group I
      patients and 6 (19%) group II patients; in group III, voiding was synergic in all
      patients. In 10 cases, CM alone was carried out both under anesthesia and in the
      waking state; anesthesia suppressed detrusor hyperreflexia (DH) in all 9 patients
      but produced no change in bladder compliance. CONCLUSIONS: In children with
      urinary disorders, urodynamic study under GA following cystourethroscopy is a
      feasible method for assessing EUS function and documenting DSD; DH is not
      evaluable, however. Stratifying urinary management on the basis of these
      examinations resulted in satisfactory clinical outcomes.

PMID- 9179665
TI  - Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using
      the international prostate symptom score.
AB  - BACKGROUND: The prevalence of lower urinary tract symptoms was determined by
      survey as an initial step in estimating the significance of benign prostatic
      hyperplasia (BPH) in Asia and Australia. METHODS: The symptom index (0 to 35) and
      quality-of-life (QOL) index (0 to 6) of the international prostate symptom score
      were measured in 7588 men in 9 Asian countries and 146 men in Australia. RESULTS:
      The percentages of Asian men considered to be symptomatic (symptom index > or =
      8) were 18%, 29%, 40%, and 56% in the age groups of 40 to 49, 50 to 59, 60 to 69,
      and 70 to 79 years, respectively. For Australian men, these figures were 36%,
      33%, and 37% in the 50 to 59, 60 to 69, and 70 to 79 year age groups,
      respectively. CONCLUSIONS: Our estimates indicate that the prevalences of
      symptomatic men in Asia and Australia are similar to or greater than those in
      Europe and America, and suggest BPH is similarly common in these areas.

PMID- 9179667
TI  - Complications and reimplantation of penile implants.
AB  - BACKGROUND: Complications of penile prosthesis implants can be divided into
      surgical and mechanical failure. We investigated penile prosthesis implants to
      clarify the surgical and mechanical complications that have arisen in our
      clinical experience. METHODS: In the 11 years between 1984 and 1995, 83 penile
      prostheses were implanted in 74 patients ranging from 37 to 82 years of age.
      RESULTS: Of the 64 malleable and mechanical prostheses, 11 were extracted,
      including 4 removed because of surgical complications and 2 due to mechanical
      failure. Of the 19 inflatable prostheses, 6 were removed, including 1 extracted
      due to surgical complication and 5 extracted due to mechanical failure. Nine
      reimplantations for 8 patients were performed and all these cases had good
      results. As a result, 66 out of 74 patients could have coitus after prosthetic
      surgery. CONCLUSIONS: Penile prosthetic surgery is an established method of
      treating organic impotence, however, it should only be considered for selected
      and well-informed patients to avoid complications and revision surgery.

PMID- 9179666
TI  - Cisplatin, vincristine, methotrexate, peplomycin, etoposide (COMPE) therapy for
      disseminated germ cell testicular tumors.
AB  - BACKGROUND: The advent of cisplatin rendered disseminated testicular germ cell
      tumor an often curable malignant disease. Patients with a heavy metastatic
      burden, however, remain poor risks; furthermore, many patients experience nausea
      or other adverse events. This paper reports a trial of a cisplatin-based (COMPE)
      combination chemotherapy regimen based on synchronization theory. METHODS: Twenty
      patients with disseminated germ cell testicular tumors were treated with COMPE;
      any residual tumor mass was surgically resected. RESULTS: Seventeen patients
      (85%) achieved complete remission by chemotherapy. The actuarial overall and
      cause-specific 3-year survival rates were 89% and 94%, respectively. In the
      subset of 16 "good-risk" patients, all remain alive after a median follow-up of
      43 months. Complications were quite tolerable, with nephrotoxicity in particular
      being extremely mild. CONCLUSION: COMPE is an effective chemotherapy regimen in
      patients with disseminated germ cell testicular tumors. Complications arising
      from this therapy are mild.

PMID- 9179668
TI  - Application of the interferon minipellet to human renal cell carcinoma in nude
      mice.
AB  - BACKGROUND: The interferon (IFN) minipellet is a sustained-release formulation of
      human lymphoblastoid IFN, with atelocollagen used as the carrier material. We
      evaluated the antitumor effect of the IFN minipellet on an established human
      renal cell carcinoma cell line (KU-2) transplanted in nude mice. METHODS: The
      treatment was started when tumor nodules had grown to 6 to 8 mm in diameter. The
      IFN minipellet, or an aqueous solution of IFN, was given by subcutaneous
      injection, or peritumor injection, on days 1 and 10. Antitumor effects were
      evaluated according to tumor weights calculated as (long diameter) x (short
      diameter)2/2 in 7 groups consisting of 6 mice each. RESULTS: IFN levels remained
      detectable in both tumor tissue and serum up to 10 days after peritumor injection
      of the IFN minipellet. Administered by the peritumor route, the IFN minipellet
      inhibited growth of the tumor significantly as compared with tumor growth in the
      untreated mice. The IFN minipellet showed greater inhibition of tumor growth by
      peritumor injection compared to subcutaneous injection. The aqueous solution of
      IFN was not effective either by subcutaneous or by peritumoral injection.
      CONCLUSION: Results indicate that the IFN minipellet is useful in the treatment
      of renal cell carcinoma.

PMID- 9179669
TI  - Calcium independent contraction of bladder smooth muscle.
AB  - BACKGROUND: Recently, it has been suggested that in vascular smooth muscle a
      Ca(2+)-independent mechanism or Ca(2+)-sensitization of contractile elements may
      participate in smooth muscle contraction. In this study, we evaluate this
      mechanism in detrusor muscle. METHODS: Strips of smooth muscle from rabbit aorta,
      rabbit bladder and human bladder were evaluated by in vitro contraction studies.
      RESULTS: The results show that (1) in Ca(2+)-free solution containing
      ethyleneglycol bis (-aminothylether)-N,N,-tetraacetic acid (EGTA), carbachol and
      phorbol ester produced sustained contractions in detrusor muscle (Ca(2+)-free
      contraction); (2) depletion of Ca2+ stores by caffeine did not affect Ca(2+)-free
      contraction induced by carbachol; and (3) W-7 (calmodulin inhibitor) and ML-9
      (myosin light chain kinase [MLCK] inhibitor) did not show inhibitory effects on
      Ca(2+)-free contraction, while H-7 (protein kinase C. [PKC] inhibitor) abolished
      this contraction. CONCLUSIONS: These results suggest that neither stored Ca2+ nor
      the Ca(2+)-calmodulin-MLCK system is involved in the carbachol-induced Ca(2+)
      free contraction of detrusor muscle. This Ca(2+)-independent contraction seems to
      be mediated by the activation of PKC coupled with agonist stimulation of the
      muscarinic receptor.

PMID- 9179671
TI  - Correlation of allelic loss of the P53 gene and tumor grade, stage, and malignant
      progression in bladder cancer.
AB  - BACKGROUND: We examined loss of heterozygosity (LOH) of the P53 gene in bladder
      cancer, and investigated the role of the P53 gene on malignant progression of
      papillary tumors. In addition, the clonality of recurrent bladder cancer was
      examined. METHODS: LOH of the P53 gene was analyzed in 67 bladder cancers from 47
      patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues,
      amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53
      gene, and analyzed with nonradioisotopic single-strand conformation polymorphism
      (Non-RI SSCP) analysis. RESULTS: Out of 40 informative samples, LOH was detected
      in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and
      none of 10 in grade 1 (10%). Statistical significance was observed between the
      LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing
      malignant progression revealed that 3 (60%) showed an LOH in the primary tumor,
      and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19
      (16%) not showing malignant progression. Four cases with metachronous recurrence
      exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both
      tumors. CONCLUSIONS: The alterations of the P53 gene were considered to correlate
      with tumor grade, and contribute to the malignant progression of bladder cancer.
      LOH in the P53 gene may serve as a clinical indicator for prognosis in
      superficial bladder cancer.

PMID- 9179670
TI  - Immunohistochemical study of tumor-infiltrating lymphocytes before and after
      intravesical bacillus Calmette-Guerin treatment for superficial bladder cancer.
AB  - BACKGROUND: This study investigated changes in the phenotypic characteristics of
      tumor-infiltrating lymphocytes during intravesical bacillus Calmette-Guerin (BCG)
      treatment using an immunohistochemical technique. METHODS: A total of 16 patients
      with superficial bladder cancer underwent intravesical BCG treatment for
      therapeutic purposes. Tissue specimens were obtained from these patients before
      and after BCG treatment by cold cup biopsies. RESULTS: The numbers of CD3+ cells,
      CD4+ cells, CD8+ cells, and CD19+ cells significantly increased after treatment
      compared with numbers before treatment (P < 0.01). Although gamma/delta T cells
      were not observed before treatment, they appeared after treatment in 6 patients.
      In all these patients, the tumors disappeared or their size was reduced by more
      than 50%, and none of the tumors recurred. The induction of CD25+ cells after
      treatment was seen in 11 of the 16 patients. CONCLUSION: gamma/delta T cells may
      play an important role in the immune response of the host to the tumor in
      intravesical BCG treatment (although this correlation was statistically
      insignificant.

PMID- 9179672
TI  - Aldosterone-producing adrenocortical carcinoma metastases found seven years after
      adrenalectomy.
AB  - We report a case of metastatic adrenocortical carcinoma detected 7 years after
      adrenalectomy. A 52-year-old woman, who had undergone adrenalectomy for an
      aldosterone-producing adrenocortical carcinoma at age 45, was found on
      examination by computerized tomography to have enlarged paraaortic lymph nodes.
      These nodes were surgically resected, and the histological diagnosis from the
      resected tissue was metastatic adrenocortical carcinoma. The patient has now
      survived for more than 9 years following the original adrenalectomy. Evidence
      suggests that this was a slow-growing tumor, because the primary tumor was
      sharply demarcated and the metastases were found 7 years after the original
      operation. We believe that aggressive surgical resection of metastatic lesions
      could lead to prolonged survival in patients with adrenocortical carcinomas of
      this type.

PMID- 9179673
TI  - Idiopathic and spontaneously regressing thrombus in right renal vein and inferior
      vena cava.
AB  - We present the case of a 57-year-old woman with a thrombus in the right renal
      vein and the inferior vena cava that disappeared spontaneously during 6 months of
      observation. She had no thrombus-related disease such as kidney cancer,
      dehydration, multiple myeloma, nephrotic syndrome, or abnormal coagulability.
      While various examinations were being performed over a 2 month period the
      thrombus regressed spontaneously. After 6 months of follow-up the thrombus could
      not be seen on abdominal computerized tomography scan. Twenty months after
      disappearance of the thrombus the patient is doing well and has no recurrence of
      thrombus.

PMID- 9179674
TI  - Bilateral chromophobe cell renal carcinoma in tuberous sclerosis complex.
AB  - We report on a patient with tuberous sclerosis complex and polycystic kidney
      disease who developed bilateral chromophobe cell renal carcinoma. We discuss the
      tuberous sclerosis complex, associated bilateral renal cell carcinoma, polycystic
      kidney disease and chromophobe cell renal carcinoma; a recently established
      subtype with a rather favorable prognosis. In a patient with tuberous sclerosis
      complex and multiple space-occupying lesions, a diagnosis of angiomyolipoma
      should be considered first but bilateral and/or multifocal renal cell carcinoma
      is a likely diagnosis.

PMID- 9179675
TI  - Renal angiosarcoma: a case report.
AB  - We report the first case of angiosarcoma in the kidney occurring in a woman; the
      tumor was initially believed to be renal cell carcinoma. This malignant tumor was
      discovered in a patient with macrohematuria. The final diagnosis was confirmed by
      histologic and immunohistochemical findings. A review of the literature on this
      tumor is also included in the discussion.

PMID- 9179676
TI  - Malignant melanoma of the kidney presenting as a primary tumor.
AB  - We report a case of malignant melanoma of the kidney presenting as a primary
      tumor. This tumor was found incidentally in a 74-year-old woman. The patient
      underwent a right radical nephrectomy, and has been living tumor free for 2 years
      and 3 months. This is the first reported case of primary renal malignant
      melanoma. We discuss the probability that this tumor is renal in origin and
      directly linked to the origin of malignant melanoma.

PMID- 9179677
TI  - Primary adenocarcinoma in the urethrorectal fistula.
AB  - A 60-year-old Japanese man was hospitalized because of urinary leakage from the
      anus on October 3, 1994. Retrograde urethrography detected a fistula between the
      bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the
      urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma.
      Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were
      performed. Pathological examination revealed primary adenocarcinoma in the
      fistula with invasion to the prostatic urethra and bladder wall. The patient
      showed no evidence of a recurrence as of August, 1996.

PMID- 9179678
TI  - Unsuspected rectal adenocarcinoma causing a urinoma.
AB  - A middle-aged man with a history of Hodgkin's disease presented with loin pain
      and microscopic hematuria. Radiologic studies demonstrated a urinoma secondary to
      ureteric obstruction at the pelvic brim. Percutaneous nephrostomy was performed
      to decompress the collection and a ureteric stent inserted to maintain drainage.
      Laparotomy revealed an unsuspected rectal adenocarcinoma. A metastatic deposit
      compressing the ureter had produced the urinoma. Metastatic colorectal carcinoma
      is a rare cause of urinoma.

PMID- 9179679
TI  - Neurogenic bladder may be a side effect of focus resection in an epileptic
      patient.
AB  - A 34-year-old man with intractable epilepsy was treated by focus resection. The
      resected volume of neocortex in the left supracallosal part of the medial frontal
      gyrus was 7 x 1 x 2.5 cm. The treatment was effective and epileptic attacks
      completely disappeared. However, the patient developed urinary incontinence
      postoperatively without any other new neurological abnormalities. Urodynamic
      study revealed loss of bladder sensation, increased bladder capacity, involuntary
      detrusor contraction, and synergic external sphincter. The suprcallosal part of
      the medial frontal gyrus has been reported to include 1 of the suprapontine
      micturition centers. In this case, resection of this area significantly affected
      bladder function. Loss of bladder sensation and increased threshold volume on
      micturition are characteristic signs of deficit in this area.

PMID- 9179680
TI  - Metastasis of prostate adenocarcinoma to testis.
AB  - Metastatic carcinoma to the testis is very rare. Metastasis of prostate
      adenocarcinoma to testis was detected incidentally after bilateral orchiectomy
      for hormonal management of metastatic prostate carcinoma. The metastatic lesion
      was not identified in physical examination or in macroscopic dissection of the
      testis after surgery. Microscopy revealed an adenocarcinoma which, given the
      history of the patient and a positive immunohistochemical stain for PSA, was
      identified as metastatic prostatic adenocarcinoma.

PMID- 9179681
TI  - Urethral recurrence of an urachal carcinoma: a case report.
AB  - A 68-year-old man presented with microscopic hematuria. Cystoscopy revealed a
      papillary and pedunculated tumor in the bladder dome which, on punch biopsy,
      proved to be adenocarcinoma. Partial cystectomy and urachal remnant resection
      were performed. Histopathologically, the tumor was diagnosed as an urachal tumor.
      Four months after surgery, multiple posterior urethral tumors were found; punch
      biopsy revealed adenocarcinoma, which was quite similar to the previous tumor.
      Based on the histopathological examination of the transurethrally resected
      tissue, the urethral tumor was diagnosed as a recurrence of the urachal
      carcinoma. No evidence of either tumor recurrence or metastasis was found within
      the 15 months following the second surgery.

PMID- 9179682
TI  - Neural control of the lower urinary tract.

PMID- 9179684
TI  - Percutaneous treatment of transitional cell carcinoma of the upper urinary tract.
AB  - BACKGROUND: We evaluated the long-term effect of percutaneous resection in 2
      Japanese patients with transitional cell carcinoma of the renal pelvis, and
      reviewed the medical literature on similar patients, to determine the appropriate
      indications for percutaneous treatment of transitional cell carcinoma in the
      upper urinary tract. RESULTS: Indications for endoscopic resection in the 2
      patients were renal insufficiency and unsuitability for major open surgery. The
      patients had no recurrence during follow-up. Seven previous reports described
      percutaneous resection of upper urinary tract transitional cell carcinoma in 82
      patients. Although 72.6% of the patients were successfully treated by
      percutaneous resection, half of the patients with grade 3 carcinoma developed
      recurrence. CONCLUSION: These results, together with those of the 7 published
      reports, suggest that percutaneous resection should be limited to selected
      patients with low-grade transitional cell carcinoma.

PMID- 9179683
TI  - Preoperative localization of parathyroid adenomas using 99mTc-MIBI scintigraphy
      in patients with hyperparathyroidism.
AB  - BACKGROUND: Technetium (Tc)99m methoxyisobutyl isonitrile (99mTc-MIBI) has
      recently been introduced for parathyroid imaging, as well as for myocardial
      imaging. We studied the usefulness of 99mTc-MIBI scintigraphy for preoperative
      localization of abnormal parathyroid glands. METHODS: The usefulness of 99mTc
      MIBI scintigraphy for detection of hyperfunctional parathyroid lesions was
      evaluated in 5 patients with primary hyperparathyroidism. The results of
      localizing the abnormal glands by using 99mTc-MIBI were compared with those
      obtained by using thallium (Tl) 201-technetium (Tc) 99m (201Tl-99mTc) subtraction
      scintigraphy, computed tomography, and ultrasonography. RESULTS: The delayed (2
      hours) imaging of 99mTc-MIBI scintigraphy was highly useful for accurate
      localization of the abnormal parathyroid lesions. The diseased glands were
      detected in all cases where 99mTc-MIBI scintigraphy was used, and using 99mTc
      MIBI scintigraphy provided more information than did computed tomography,
      ultrasonography, or 201Tl-99mTc subtraction scintigraphy. CONCLUSION: This method
      is simple and essential for detecting hyperfunctioning parathyroid glands,
      especially those with small or ectopic lesions. This technique should be widely
      applied as a localizing diagnostic method for hyperparathyroidism.

PMID- 9179685
TI  - Functional outcome and late complications in patients with continent urinary
      reservoirs.
AB  - BACKGROUND: We reviewed the functional outcome and late complication of continent
      urinary reservoirs (CUR) constructed with a cecocolonic segment, including the
      Indiana pouch, in 37 patients treated in our clinic. METHODS: The CUR procedure
      was performed on 37 patients, creating partially detubularized (PD) reservoirs in
      9 patients, totally detubularized (TD) reservoirs in 16 patients and reservoirs
      with an ileal patch (IP) in 12 patients. Continence was achieved by the nipple
      valve in 10 patients and by ileal plication in 27 patients. The mean follow-up
      period was 46 months (range, 15 to 87 months). The function of the reservoir was
      evaluated by measurement of the intrareservoir pressure. RESULTS: Patients with
      the TD reservoir had less frequent appearance of involuntary, phasic elevation of
      the intrareservoir pressure (30.8%) than those with the PD reservoir (62.5%). In
      contrast, this phasic elevation was found in only 1 patient with an IP reservoir.
      The IP reservoir had the largest capacity accompanied by the lowest maximum
      intrareservoir pressure. Total incontinence was observed in 2 patients with ileal
      plication due to disruption of the plicated sutures on the terminal ileum.
      Frequent difficulty in catheterizing the reservoir was found in 2 patients, and
      reservoir-ureter reflux was found in 3 renal units. The serum chloride level was
      significantly elevated after surgery, however, in most patients the levels
      remained within normal limits. CONCLUSION: Our experience of the outcome and late
      complications of reservoirs indicates that the cecocolonic reservoir with an
      ileal patch and stapled ileal plication, i.e., the Indiana pouch, is a better
      choice for continent urinary diversion for patients who need a cystectomy.

PMID- 9179686
TI  - Recurrence of primary superficial bladder cancer treated with prophylactic
      intravesical Tokyo 172 bacillus Calmette-Guerin: a long-term follow-up.
AB  - BACKGROUND: Long-term results after transurethral resection (TUR) and
      prophylactic intravesical Tokyo 172 bacillus Calmette-Guerin (BCG) therapy for
      primary superficial bladder cancer were analyzed by multivariate analysis, and
      factors affecting the recurrence of bladder tumors after this therapy were
      examined. METHODS: One-hundred and forty-one consecutive patients with primary
      superficial bladder cancer who consulted the Department of Urology at Wakayama
      Medical College and affiliated hospitals between May 1985 and May 1990 were
      studied. Tokyo strain BCG was given intravesically (80 mg in 40 ml saline) weekly
      for 6 weeks. RESULTS: The 5-year cumulative recurrence-free rate by the Kaplan
      Meier method was 0.702 in 141 patients with primary superficial bladder cancer.
      The 5-year recurrence-free function using the proportional hazard model was
      0.743. Using the Cox proportional hazard model, variables that significantly
      contributed to recurrence after intravesical BCG included female sex, tumor size
      less than 1 cm in diameter, and T1 tumor stage. Patient age, tumor type,
      multiplicity, tumor grade, and concomitant carcinoma in situ did not contribute
      to recurrence. CONCLUSION: Long-term results showed that prophylactic
      intravesical Tokyo strain BCG after TUR for primary superficial bladder cancer is
      also effective in preventing the recurrence of bladder cancer, and the biologic
      behavior of superficial bladder cancer other than stage T1 tumor may be altered
      after intravesical BCG.

PMID- 9179687
TI  - Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer:
      an interim report on short-term effects. Prostate Cancer Study Group.
AB  - BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical
      radicality and/or patient prognosis in prostate cancer. METHODS: Patients with
      clinical stage A2, B, and C prostate cancer were randomized to either group I (n
      = 113) or group II (n = 111). Group I patients were to receive preoperative
      endocrine therapy consisting of leuprolide and chlormadinone for 3 months,
      followed by radical prostatectomy with lymph node dissection. Group II patients
      were to undergo the surgery before endocrine therapy. RESULTS: Group I patients
      showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE:
      41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to
      21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed
      a significant difference in the rates of down-staging (19.1% in group I versus
      3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive
      lymph node metastasis (20.7% versus 36.5%). No significant difference was
      detected in operating features. Subgroup analyses indicated that beneficial
      effects were correlated positively with degree of histologic differentiation and
      negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy
      reduced local extension of prostate cancer, and the effects depended on
      histologic differentiation and PSA level. Long-term follow-up data are needed to
      determine the effects on the patient prognosis.

PMID- 9179688
TI  - Biplane planimetry as a new method for prostatic volume calculation in
      transrectal ultrasonography.
AB  - BACKGROUND: We developed a new prostatic volume calculation method using the full
      information obtained from biplane transrectal ultrasonogram. METHODS: Based on
      the cross and sagittal contours, a model composed of sequentially arranged copies
      of the cross sections, which are reduced so that the anteroposterior diameters of
      the copies fit the contour of the sagittal section, was created. The volume of
      this model was the sum of the square of the reduced rates of the height
      multiplied by the area of the maximum cross section and by slice thickness.
      Sonograms of 150 patients who underwent ultrasonography with a transrectal chair
      type probe were used for the comparison of this method with the ellipsoid volume
      calculation and the prolate ellipse volume calculation methods. The step-section
      planimetric volume calculation method was used as the gold standard. RESULTS:
      This new method showed the least difference from the step-section planimetry
      among the 3 calculation methods evaluated. CONCLUSION: The formula of the new
      method is very simple, so it is easy for it to be incorporated in ultrasonic
      consoles that are capable of measuring distance and area.

PMID- 9179689
TI  - Testosterone replacement therapy for male hypogonadism with a radiation
      polymerized testicular prosthesis.
AB  - BACKGROUND: The effect of an artificial testicular prosthesis on sexual
      disturbance in hypogonadal men was investigated. METHODS: Twelve hypogonadal men
      were treated with testosterone replacement therapy delivered via radiation
      polymerized testicular prostheses surgically implanted in their scrotums.
      RESULTS: An average serum testosterone level of over 200 ng/dL was maintained for
      48 months. Most patients treated with this prosthesis were satisfied with the
      improvement of their sexual activity. Moreover, the patients were psychologically
      more satisfied with the enlarged scrotum achieved with the implanted prosthesis.
      CONCLUSION: We recommend this prosthesis as the first choice among testosterone
      replacement therapies for hypogonadal men.

PMID- 9179690
TI  - Biochemical modulation of 5-fluorouracil with murine interferon-alpha/beta
      against murine renal cell carcinoma.
AB  - BACKGROUND: Conventional therapy for renal cell carcinoma using interferon (IFN)
      has shown limited antitumor action. The purpose of our study was to investigate
      synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate
      the mechanisms of interaction between the 2 agents in mice. METHODS: Antitumor
      effects and biochemical modulation of murine IFN-alpha/beta and 5-FU were
      determined against the murine renal cell carcinoma cell line, Renca, in vivo. The
      activity of thymidylate synthetase and thymidine kinase was measured using
      cytosolic extracts of the tumors. RESULTS: Combination treatment with IFN
      alpha/beta and 5-FU produced a significant enhancement of growth inhibition
      against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the
      total amount of thymidylate synthetase and an 11.6-fold increase in the
      thymidylate synthetase inhibition rate, while the administration of IFN
      alpha/beta did not significantly reduce the 5-FU-induced increase in thymidylate
      synthetase. The administration of IFN-alpha/beta decreased thymidine kinase
      activity to 65.5% maximally, compared with that in the control mice or the mice
      treated with 5-FU. CONCLUSIONS: The reduction of thymidine kinase caused by
      treating the mice with IFN-alpha/beta changes the utilization of exogenous
      thymidine for DNA synthesis, and may represent the mechanism of the additive
      antitumor effect of the 2 agents, through the suppression of the salvage pathway
      for deoxythymidine monophosphate induction.

PMID- 9179691
TI  - Absence of RET proto-oncogene mutations in a father and son with pheochromocytoma
      and pancreatic islet cell tumor.
AB  - BACKGROUND: We describe a father and son with a combination of pheochromocytoma
      and pancreatic islet cell tumor. Although its familial occurrence is rare, this
      syndrome could be called overlapping-type multiple endocrine neoplasia (MEN),
      since it fulfills the criteria for both type 1 and type 2 MEN. Recently, germ
      line mutations of the RET proto-oncogene (RET) were found to be related to
      tumorigenesis and disease phenotypes in type 2 MEN. METHODS: Using polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we
      looked for germ line mutations of RET in 8 members of this family, including the
      2 patients. RESULTS: Analysis of RET exons 10, 11 and 16, which contain the hot
      spot codons for MEN type 2, revealed no mutations in any individual examined.
      CONCLUSION: These findings suggest that these 3 exons in RET are not related to
      tumorigenesis in overlapping-type MEN.

PMID- 9179692
TI  - PCNA and p53 in urinary bladder cancer: correlation with histological findings
      and prognosis.
AB  - BACKGROUND: This study aimed to immunohistochemically examine the expression of
      proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell
      carcinomas (TCC) of the urinary bladder, and to investigate possible correlations
      of this expression with the tumor grade or stage, tumor recurrence, and prognosis
      of the disease. MATERIALS AND METHODS: The immunohistochemical status of the PCNA
      and p53 proteins were determined on paraffin-embedded sections from 128 patients
      with TCC of the urinary bladder, using PC-10 and DO7 as the primary antibodies.
      Positive stainings were represented by scores (Labeling Index; LI, %) calculated
      as the percent of positive cells among all neoplastic cells counted. The findings
      were compared to the patients' histopathological features. Patients who underwent
      transurethral resection were divided into groups with "low" and "high" scores for
      PCNA and p53, respectively, and the tumor recurrence rate was compared among the
      groups. Patients who underwent total cystectomy were similarly divided into "low"
      and "high" score groups, and survival rates of the groups were compared. RESULTS:
      PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling
      index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%),
      with a mean labeling index of 35.3%. There were significant correlations of the
      PCNA and p53 indices with both histological grade and stage of the tumor. In the
      TUR group, there were no statistically significant differences in recurrence rate
      between the groups with high or low scores for either PCNA or p53. In the total
      cystectomy group, there was a significant correlation between survival rate and
      positive staining for PCNA, but not for p53. The relationship between 2
      parameters, PCNA and p53 scores, was not significant (linear correlation
      coefficient, r = 0.67). CONCLUSIONS: PCNA and p53 status in transitional cell
      carcinomas of the urinary bladder is related to the histopathological findings.
      We also suggest that immunohistochemical staining for PCNA provides significant
      clinical information which may be useful in the initial selection of therapy.
      However, overexpression of p53 does not appear to represent an independent
      prognostic marker in bladder tumors.

PMID- 9179693
TI  - Screening of H-ras gene point mutations in 50 cases of bladder carcinoma.
AB  - BACKGROUND: Mutation converts the H-ras gene into an activated oncogene in about
      10% of human bladder cancers. Codons 12 and 61 are the major "hot spots" for
      activation. A simple and accurate method to detect point mutations in these
      codons may be clinically useful for early diagnosis of bladder cancer. METHODS:
      Bladder cancer samples from 50 patients, plus 10 samples of normal bladder
      mucosa, were analyzed for possible point mutation of the H-ras gene at either
      codon 12 or codon 61. The H-ras gene DNA segments that include these 2 codons
      were amplified by PCR methods, then the possible presence of a point mutation was
      evaluated at each codon by susceptibility of the respective DNA segments to
      digestion with the restriction enzyme and by dot blot hybridization assay. A
      bladder cancer patient who had an H-ras gene mutation was examined to see whether
      the mutation was also detectable in the cells released in the urine. RESULTS:
      Definite or possible point mutations were found in 6 (12%) out of 50 bladder
      cancer patients, while no mutation was detected in normal mucosa. A point
      mutation could also be detected in cells isolated from the patient's urine
      sample. CONCLUSION: The prevalence of point mutations at codon 12 or codon 61 of
      the H-ras gene found in this study was similar to that previously estimated for
      human bladder cancer by DNA transfection assay. The method we have used for
      detecting point mutations of the H-ras gene provides a simple and highly accurate
      way to detect mutated cancer cells even in the urine. It may be clinically usable
      for early diagnosis of bladder cancer.

PMID- 9179694
TI  - Morphological and pharmacological characterization of guinea-pig prostatic smooth
      muscle cells in vitro.
AB  - BACKGROUND: Prostatic smooth muscle is thought to play a major role in the
      pathogenesis of bladder outlet obstruction in patients with benign prostatic
      hypertrophy. However, the physiology of prostatic smooth muscle cells remains
      largely unknown, in part due to the lack of a suitable model system. We therefore
      sought to establish an in vitro culture of guinea pig prostatic smooth muscle
      cells. METHODS: Immature guinea pig prostate was treated by enzymatic digestion
      and the cells obtained were used to initiate the primary culture. After 3 to 4
      passages, cultured smooth muscle cells were examined morphologically by
      immunocytochemistry and electron microscopy. The contractile properties of
      cultured smooth muscle cells were also examined. RESULTS: The cultured prostatic
      cells demonstrated hill and valley morphology, which is a hallmark of smooth
      muscle cells in vitro, and stained positively for desmin. In addition, electron
      microscopic examination of ultrastructural morphology revealed myofilaments.
      Confluent cultures of prostatic smooth muscle cells showed a clear, dose
      dependent contractile response to phenylephrine. Furthermore, contraction of the
      prostatic smooth muscle cells by 10(-6) mol/L phenylephrine was completely
      inhibited by pretreatment with 10(-6) mol/L terazosin. CONCLUSIONS: An in vitro
      culture of prostatic smooth muscle cells was established. This culture is likely
      to provide a powerful tool for elucidating the physiology and pathophysiology of
      prostatic smooth muscle.

PMID- 9179696
TI  - Y chromosome (Yq11) microdeletions in idiopathic azoospermia.
AB  - BACKGROUND: Cytogenetic anomalies and molecular deletions of the Y chromosome in
      idiopathically sterile men suggest that genetic factor(s) controlling
      spermatogenesis are located in the distal portion of Yq11. We studied Y
      chromosome microdeletions in the Yq11.23 region in idiopathic azoospermia.
      METHODS: We studied 25 azoospermic male patients with a cytogenetically normal
      46XY karyotype; 13 exhibited Sertoli-cell-only syndrome and 12 exhibited
      maturation arrest. Microdeletions in the Yq11 region were examined using the PCR
      technique with 4 pairs of primers from DNA loci in Yq11.23. RESULTS:
      Microdeletions in Yq11.23 were detected in 4 of the 25 azoospermic men. The most
      common deletion was of the Y6HP52pr sequence, which was detected in 3 of 13 men
      with Sertoli-cell-only syndrome but in only 1 of 12 with maturation arrest.
      CONCLUSION: Detection of microdeletions within the Yq11 sequence is an important
      clue to the genetic factor(s) underlying azoospermia.

PMID- 9179695
TI  - Role of ATP and related purine compounds on urethral relaxation in male rabbits.
AB  - BACKGROUND: Non-adrenergic, non-cholinergic (NANC) relaxation evoked by
      electrical field stimulation (EFS) has been observed in the urethra, with nitric
      oxide (NO) considered the agent most probably mediating this effect. However,
      Burnstock's purinergic hypothesis suggests that ATP and related purine compounds
      are neurotransmitters in NANC relaxation, although the physiological and
      pharmacological effects of ATP and related purine compounds in the urethra have
      been little studied. METHODS: The effects of ATP and related purine compounds, NG
      nitro-L-arginine (NOARG; an inhibitor of nitric oxide synthesis from L-arginine),
      calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal
      polypeptide (VIP) on relaxation and smooth muscle tension induced by electrical
      field stimulation (EFS) were studied in isolated male rabbit circular urethral
      smooth muscle (functional study). In addition, the outflow of ATP elicited by EFS
      was measured using the luciferase technique (superfusion study). All experiments
      were performed in the presence of guanethidine (3 x 10(-3) mol/L) and atropine
      (10(-6) mol/L). RESULTS: In preparations contracted with U46619, a prostaglandin
      peroxidase inhibitor, ATP had almost no effect on EFS-induced relaxation;
      however, suramin, a non-selective P2Y-purinoceptor antagonist, and NOARG each
      markedly attenuated this relaxation in a concentration-dependent manner. ATP and
      related purine compounds (adenosine, AMP and ADP) each reduced U46619-induced
      tonic contraction in a concentration-dependent manner. The potencies of the
      relaxant effects of ATP and these purine compounds were almost the same. In
      preparations contracted with U46619, CGRP and substance P had no effect on tonic
      contraction, but VIP reduced tonic contraction in a concentration-dependent
      manner. In the superfusion study, the outflow of ATP into the superfusate was
      markedly increased by EFS. When NOARG or prazosin was added to the superfusate,
      the increase in outflow of ATP was unchanged, but when suramin was added to the
      superfusate, no increase in outflow of ATP was observed. CONCLUSIONS: These
      findings suggest that P2Y-purinoceptors exist in the male rabbit urethra, and
      that ATP and related purine compounds may play a role in non-adrenergic, non
      cholinergic neurotransmission. Consequently, the pathways mediating urethral
      relaxation by ATP, NO and VIP may be different.

PMID- 9179697
TI  - Treatment of crush syndrome patients following the great Hanshin earthquake.
AB  - Five of 8 patients with rhabdomyolysis treated at our hospital following the
      Great Hanshin Earthquake were diagnosed with crush syndrome. One patient with
      crush syndrome and 3 patients with rhabdomyolysis and no renal dysfunction
      recovered with conservative therapy, while 1 crush syndrome patient recovered
      with peritoneal dialysis (PD). Of the 3 patients who died, 2 had undergone
      continuous arterio-venous hemofiltration (CAVH). We examined the laboratory data
      to identify any factors that may be prognostic for crush syndrome. The serum
      amylase levels were significantly higher and the levels of aspartate transaminase
      (AST) and lactic dehydrogenase (LDH) tended to be higher from the patients who
      died. Examination of the serum amylase, AST and LDH levels may be useful for
      assessing the prognosis in patients with crush syndrome.

PMID- 9179698
TI  - Horseshoe kidney with retrocaval ureter and ureteropelvic junction obstruction: a
      case report.
AB  - We report a rare disorder, horseshoe kidney accompanied by retrocaval ureter and
      ureteropelvic junction obstruction, in a 42-year-old man. This is the third case
      in the world literature.

PMID- 9179699
TI  - Kidney-alone transplantation in diabetic patients with end-stage renal disease.
AB  - From January 1989 to December 1995, 5 diabetic patients with end-stage renal
      disease (1 woman, 4 men) underwent kidney-alone transplantation. The mean age of
      the recipients at the time of transplantation was 37.4 years (range, 32 to 43).
      Craft function and glucose tolerance was evaluated for 5 to 72 months after
      surgery. Postoperative complications were seen in 2 patients; nonspecific
      subcutaneous infections and an asymptomatic partial allograft infarction. All
      renal allografts were functioning 1 year after transplantation, with a mean serum
      creatinine level of 1.10 mg/dL (range, 0.8 to 1.8 mg/dL), and a mean urinary
      protein level of 17.8 mg/dL (range, 5 to 27 mg/dL). The postoperative daily dose
      of insulin was higher than the preoperative dose, while the level of glycated
      hemoglobin (HbA1C) increased after surgery and peaked 6 months after
      transplantation; 1 year after transplantation it had reverted to the preoperative
      level. As long as the diabetic complications of the renal allograft recipients
      are not severe, the short-term survival and the renal function of diabetic
      patients with end-stage renal disease improves after kidney-alone
      transplantation, which is still the standard method of treatment in Japan.

PMID- 9179700
TI  - Three approaches for laparoscopic unroofing of simple and complicated renal
      cysts.
AB  - We report 2 cases of simple renal cysts which were marsupialized with 2
      laparoscopic approaches involving either transperitoneal, with reflection of the
      colon medially or dissection through the mesocolon, and a case of a multilocular
      renal cyst which was treated by the retroperitoneal approach. Although
      laparoscopic unroofing of a renal cyst is a safe and effective alternative to
      open surgical techniques, the transperitoneal approach should only be used for
      simple renal cysts. The retroperitoneal approach for complicated renal cysts may
      be indicated if preoperative examinations exclude the possibility of malignancy.

PMID- 9179701
TI  - Primary retroperitoneal teratoma in an adult: a case report.
AB  - A primary retroperitoneal teratoma is a relatively rare neoplasm in adults. We
      report 1 such case evaluated by CT and MRI scans. The preoperative MRI was
      important in that it delineated the precise position of the tumor relative to the
      surrounding organs.

PMID- 9179702
TI  - "Collision phenomenon" of prostate and bladder cancers in lymph node metastases.
AB  - We report here the case of a 78-year-old man who, 15 months after orchiectomy for
      palliation of prostate adenocarcinoma, was diagnosed as having squamous cell
      carcinoma of the urinary bladder. The bladder cancer was treated surgically,
      including dissection of pelvic lymph nodes. Some of these nodes were observed at
      surgery to be swollen, and were found on pathologic examination to exhibit the
      collision phenomenon: the mixing and mingling of cancer cells representing 2
      distinct topographic origins. This case suggests that the possibility of
      collision phenomenon should be considered whenever any metastasis (but especially
      one in the lymph nodes) is found in a patient diagnosed with 2 different types of
      cancer. Moreover, it reminds us that diagnosis of one type of cancer does not
      rule out the possibility of another.

PMID- 9179703
TI  - Malignant mesenchymoma of the spermatic cord with a brief review of the
      literature.
AB  - Sarcomas of the spermatic cord are rare, and malignant mesenchymomas are
      particularly rare. Only 8 cases of paratesticular mesenchymoma have been
      described previously. We report here the ninth case of malignant mesenchymoma of
      the spermatic cord, in which there was a local recurrence. We also briefly review
      the previously reported cases.

PMID- 9179704
TI  - Carcinosarcoma in the region of the female urethra.
AB  - A 61-year-old woman with acute urinary retention was found to have a
      carcinosarcoma in the region of the urethra. Evaluation of the computed tomogram
      suggested a urethral tumor, which was resected by a transperineal approach. She
      received local radiotherapy after surgery, and is alive at 1-year follow-up with
      a tumor metastasis to the pelvis.

PMID- 9179705
TI  - Comparison of iodinated contrast media-induced renal vasoconstriction in human,
      rabbit, dog, and pig arteries.
AB  - RATIONALE AND OBJECTIVES: Contrast media (CM)-induced renal vasoconstriction is
      an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects
      of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar
      CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and
      compared with human tissue in an organ bath. METHODS: Isometric contractions were
      induced by increasing concentrations of CM and high-osmolar glucose solution.
      RESULTS: Contrast media and glucose elicited contractions in human renal arteries
      of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit
      and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate),
      15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose),
      respectively, of the control. There was a vasorelaxing effect of all CM tested on
      pig renal artery. CONCLUSIONS: Responses in rabbit and dog renal arteries were
      similar to those in human renal arteries and could serve as models for
      investigating CM-induced renal vasoconstriction.

PMID- 9179706
TI  - Secretory and nonsecretory pituitary adenomas are distinguishable by 1/T1
      magnetic relaxation rates at very low magnetic fields in vitro.
AB  - RATIONALE AND OBJECTIVES: The authors investigated whether hormonally active and
      inactive pituitary adenomas can be discriminated in vitro by magnetic resonance
      (MR) imaging-related data. METHODS: 1/T1 nuclear magnetic relaxation dispersion
      profiles were measured for 39 fresh surgical specimens of secreting and
      nonsecreting adenomas, classified using clinical criteria or preoperative serum
      hormone levels. Nonsecreting adenomas were subdivided into hormone-producing and
      nonhormone-producing by immunostains. At five fields (0.00024 to 1.2 tesla [T]),
      mean 1/T1 was analyzed for statistically significant differences among these
      three tumor categories. RESULTS: Mean 1/T1 was significantly higher (P < 0.02)
      for hormone-secreting than for nonsecreting adenomas at fields below 0.24 T; no
      significant difference existed at typical MR imaging fields (0.5 to 1.5 T). Mean
      1/T1 for hormone-producing and nonhormone-producing, nonsecreting adenomas were
      not significantly different at any field. CONCLUSIONS: Because 1/T1 at low fields
      is related to 1/T2 at imaging fields, it may be possible to detect hormone
      secretion of pituitary adenomas noninvasively by MR imaging.

PMID- 9179707
TI  - Effect of the menstrual cycle on gallbladder fasting volume and postprandial
      emptying in nulliparous young females.
AB  - RATIONALE AND OBJECTIVES: Reports on the effect of the ovulatory cycle on
      gallbladder motility are inconsistent. The authors investigated the gallbladder
      motor function at both phases of the menstrual cycle in humans. METHODS:
      Seventeen young, healthy, nulliparous women participated in the study.
      Gallbladder fasting volume and postprandial emptying were measured twice in each
      subject using real-time ultrasonography: one at the follicular (12th-13th day)
      and another at the luteal (21st-22nd day) phases. From the emptying curves, the
      duration of the lag phase and the ejection fraction of emptying were calculated.
      RESULTS: Fasting volume was significantly greater (P = 0.025) at the luteal (14.8
      +/- 8 mL standard deviation [SD]) than at the follicular (11.2 +/- 4.7 mL SD)
      phase. Although the lag phase duration was longer (P = 0.009) at the follicular
      (5.2 +/- 6.4 SD minutes) than the luteal (1.6 +/- 3.6 minutes SD) phase, the
      ejection fraction was significantly greater at the latter one (follicular phase:
      62 +/- 13.2% SD; luteal phase: 73.4 +/- 14% SD; P = 0.0085). CONCLUSIONS: Female
      sex hormones seem to biologically affect the gallbladder motor function.

PMID- 9179709
TI  - Phosphorus-31 chemical shift imaging of metastatic tumors located in the spine
      region.
AB  - RATIONALE AND OBJECTIVES: Phosphorus-31 magnetic resonance spectroscopy was used
      in 14 cases to examine metastases of known malignant tumors located in the spine
      region. The purpose was to test the hypothesis that tumor phosphomonoester (PME)
      is elevated. METHODS: Two-dimensional chemical shift imaging was used in
      combination with a slice-select gradient in the third dimension to obtain true
      three-dimensional localization. RESULTS: The spectral maps revealed PME signals
      increased up to 10 times in voxels containing contrast-enhancing metastatic spine
      lesions compared with adjacent areas and peripheral muscle voxels.
      Phosphomonoester increase was significant for all tumors combined (8.6 +/- 5.3
      arbitrary units versus 2.4 +/- 0.5 and 2.2 +/- 0.8 arbitrary units in unaffected
      myelum and corpora; P < 0.001), though smaller than 2 standard deviations in 5 of
      14 cases. The latter shared high proportions of phosphocreatine, phosphocreatine
      > 30% of total phosphate, indicating substantial amounts of muscle tissue
      included in the tumor voxels (partial volume effect). CONCLUSIONS: Phosphorus-31
      MR spectroscopy can be of value in the recognition of malignant vertebral column
      abnormalities. Malignant tumor is marked by drastic PME increases-fourfold to
      tenfold, provided that partial volume effects are small.

PMID- 9179708
TI  - Spirometric gated quantitative computed tomography of the lung in healthy smokers
      and nonsmokers.
AB  - RATIONALE AND OBJECTIVES: The authors investigated the influence of cigarette
      smoking on healthy, asymptomatic smokers and nonsmokers with the help of
      spirometric triggered quantitative computed tomography. In our prospective study,
      the authors compared conventional lung function parameters with the computed
      tomography values (lung attenuation, lung area). METHODS: The study group
      comprised 40 healthy volunteers consisting of 20 smokers and nonsmokers (20
      females and 20 males). The corresponding groups have been matched concerning
      their age, height, body mass, (cigarette) pack years. Computer tomography scans
      were triggered at 35%, 50%, 70% and 95% of vital capacity at a defined apical and
      a basal level. RESULTS: Functional residual capacity (FRC), total lung capacity
      and airway resistance showed close correlations to lung parenchymal attenuation
      values especially at full inspiration and expiration. For example, the authors
      found a correlation coefficient of r = -0.845 (P < or = 0.001) concerning the FRC
      and lung attenuation values in the apical lung at 35% of vital capacity in male
      smokers. Male smokers proved to have a significantly higher pulmonary lung
      density at all inspiratory states than the other groups (P < or = 0.05; Student's
      t test). Although male smokers had a higher vital capacity they showed a smaller
      cross-sectional area increase of the lung during inspiration than nonsmokers.
      This phenomenon is a result of the decreasing compliance of the smoker's lung,
      due to small airways disease and hypoxic vasoconstriction. CONCLUSIONS:
      Spirometric-triggered quantitative computed tomography has proved to be a
      sensitive diagnostic device for the investigation of early pathomorphologic
      changes in healthy, asymptomatic cigarette smokers.

PMID- 9179710
TI  - Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance
      imaging. Application to unilateral lung transplantation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the use of magnetic resonance (MR)
      to image pulmonary perfusion in healthy controls and to detect pulmonary defects
      in patients with unilateral lung transplantation, using dynamic images after
      contrast administration. METHODS: Five patients with right lung transplantation
      and nine healthy volunteers underwent MR imaging. Twenty-five subsecond contrast
      enhanced MR images (turbo-fast low-angle shot [FLASH]) were obtained at the level
      of the pulmonary arteries after a single injection of gadopentetate dimeglumine
      (0.1 mmol/kg) in an antecubital vein. Perfusion lung scintigraphy was done within
      24 hours after the MR imaging examination in the transplanted patients. RESULTS:
      Before administration of contrast material, MR images showed both lungs to be
      homogeneous and of low signal intensity in healthy controls and in patients with
      lung transplantation. After contrast administration in controls, the mean signal
      intensity of the dependent lung increased markedly to 171 +/- 24% above baseline,
      whereas the nondependent signal intensity lung increased by only 105 +/- 17%;
      these changes were significantly different. In all patients with lung
      transplantation, a clear perfusion defect was demonstrated in the native lung.
      This defect was confirmed in all cases by perfusion nuclear scintigraphy, which
      showed that the majority of lung perfusion is directed to the transplanted
      allograft, compared with the native contralateral lung. CONCLUSIONS: Our results
      suggest that dynamic contrast-enhanced MR imaging is a potential method for
      detecting pulmonary perfusion defects in patients with lung transplantation.

PMID- 9179711
TI  - Radiographic examination of the small bowel. An application of odds ratio
      analysis to help attain an appropriate mix of small bowel follow through and
      enteroclysis in a working-clinical environment.
AB  - RATIONALE AND OBJECTIVES: Simplifying data collection and analysis should promote
      utilization management in review of examinations of the small bowel in the
      general practice. METHODS: A case control format with the generation of an odds
      ratio to answer sets of binary questions derived from annual examination data is
      shown. The positive examination results applied were compared with the literature
      as a cross-checking mechanism. The examination identified as most likely to be
      positive was recommended prospectively in a protocol for the following year. Two
      of 5 years are illustrated to emphasize the development of the methodology.
      RESULTS: Application of this model in testing its validity, since 1990 at Madigan
      Army Medical Center, allows for the generation of a new protocol each year to
      prospectively improve clinical definition. CONCLUSIONS: A 5-year analysis of
      small bowel examination protocols, subdivisions, and odds ratios, will be
      forthcoming. The 2 years illustrated show how strongly our practice was
      influenced in using enteroclysis or in using the small bowel follow through as
      the examination of choice in the various clinical categories of small bowel
      disease: (1) practice was influenced by protocol and (2) outcome was steered
      toward positive examinations.

PMID- 9179712
TI  - Digital chest imaging using a selenium detector. The impact of hard copy size on
      observer performance: a computed tomography-controlled study.
AB  - RATIONALE AND OBJECTIVES: The authors compare radiologist detection performance
      under clinical conditions for assessment of the effect of size reduction on the
      diagnostic performance of digital chest images obtained with a selenium detector.
      METHODS: Sixty-five patients were examined with the digital system. The images
      were acquired without an antiscatter grid. Sixty-five posteroanterior life-size
      images (35 x 43 cm) and sixty-five posteroanterior minified images (56% of life
      size) were analyzed by three observers for detection of pulmonary, mediastinal,
      and pleural pathology, using computed tomography as the reference standard. The
      diagnostic value of life-size and minified images for the detection of these
      chest abnormalities was analyzed with receiver operating characteristic (ROC)
      methods. RESULTS: For the detection of the various abnormalities by all
      radiologists, the areas under the ROC curves with life-size images versus
      minified images, respectively, were as follows: pulmonary opacities, 0.78 versus
      0.78; interstitial disease, 0.74 versus 0.75; mediastinal disease, 0.70 versus
      0.72; and pleural abnormalities 0.72 versus 0.67. CONCLUSIONS: There was no
      statistically significant difference between the radiologists' performance in
      detecting pulmonary, mediastinal, and pleural pathology with life-size versus
      that with minified (56% of life size) digital selenium chest radiography.

PMID- 9179713
TI  - Renal tolerance of nonionic dimers in humans: how relevant are experiments in
      rats?

PMID- 9179714
TI  - Value and choice: providing consumers with information on the quality of health
      care. Conference overview.
AB  - BACKGROUND: The burgeoning topic of information for consumers on the quality of
      health care raises several questions: What kinds of information about quality of
      care do Americans want and use? How do consumers use information about quality to
      choose a health plan, hospital, or physician for themselves and their families?
      To whom do consumers turn for this information? How would we know if we have
      provided Americans the "right" information? To answer these questions, the Henry
      J. Kaiser Family Foundation and the Agency for Health Care Policy and Research of
      the U.S. Department of Health and Human Services convened a national conference,
      "Value and Choice: Providing Consumers with Information on the Quality of Health
      Care," in Arlington, Virginia, October 29-30, 1996. ISSUES AND PARTICIPANTS: The
      overview summarizes the central questions and themes emerging from commissioned
      papers, presentations, and group discussion of work in progress in a field in the
      midst of intense development. Groups and interests represented by the presenters
      and participants included academic researchers, consumer advocates, librarians,
      information technologists, health care administrators, and agency and foundation
      officials. Four articles following the overview focus on results of a national
      consumer survey, definition of the total customer relationship, emerging "self
      helpers" on the Internet, and the risks, benefits, and ultimate measures of
      success in the movement to provide consumers with information on health care
      quality. FUTURE DIRECTIONS: The matter of what consumers need to know, in
      contrast to what they receive or use now, raised the issue of multiple purposes
      and the need for a consensus development of a strategy.

PMID- 9179715
TI  - Understanding the quality challenge for health consumers: the Kaiser/AHCPR
      Survey.
AB  - BACKGROUND AND PURPOSE: "Americans as Health Care Consumers: The Role of Quality
      Information," a nationally representative telephone survey of 2,006 adults,
      designed by the Henry J. Kaiser Family Foundation (Kaiser) and the Agency for
      Health Care Policy and Research (AHCPR) of the U.S. Department of Health and
      Human Services, was presented at the Kaiser/AHCPR conference "Value and Choice:
      Providing Consumers with Information on the Quality of Care" in Arlington,
      Virginia, October 29-30, 1996. The survey was conducted by Princeton Survey
      Research Associates between July 16 and September 5, 1996, and has a margin of
      error of plus or minus 3 percentage points. RESULTS: The survey found that
      Americans value quality but that the use of quality indicators is likely to be
      only one factor in their decision making, given their reliance on and preference
      for quality information from their physicians, friends, and family. A plurality
      (42%) chose having high quality of care as their most important concern, but only
      39% reported seeing information comparing health plans, and only about one-third
      of that group said they used this information themselves to make decisions. The
      following are possible explanations for why consumers don't use information on
      quality in making health care decisions: They trust friends, families, and
      physicians about all other sources for advice; They do not (at the time of the
      survey) have many health plan choices to make; or They lack familiarity with
      comparative health care quality information.

PMID- 9179716
TI  - The total customer relationship in health care: broadening the bandwidth.
AB  - BACKGROUND: The health care system is in the midst of a market revolution, driven
      by cost containment but also fully charged by the idea that competition among
      providers will lead to reforms that neither the government nor the professions
      have been able to achieve by themselves. An agenda of "reports to consumers" has
      been advanced as a bright new hope for improving the health care system. An
      alternative to this notion of consumerism is far broader--that is the concept of
      total relationship. THE BANDWIDTH OF TOTAL RELATIONSHIP: In the hands of masters
      outside the health care domain, the total customer relationship embraces several
      elements that can be imported into health care and that offer more promise than
      "report cards," including the following: Customers as assistants in decreasing
      waste; Mass customization and stratification of need; Shaping demand; Immediate
      recovery; Delight as the objective; and Customer knowledge and innovation. A
      CREDO: The next phase of development of total customer relationship might well be
      guided by a credo including several tenets about the wisdom of those the health
      care system serves and the nature of its purpose: 1. In a helping profession, the
      ultimate judge of performance is the person helped. 2. Most people, including
      sick people, are reasonable most of the time. 3. Different people have different,
      legitimate needs. 4. Pain and fear produce anxiety in both the victim and the
      helper. 5. Meeting needs without waste is a strategic and moral imperative.

PMID- 9179717
TI  - Health online and the empowered medical consumer.
AB  - BACKGROUND: Lay health care consumers' emergence as active participants in online
      health care networks is a powerful new technological pattern that promises to
      take the American health care system through all stages of cultural adaptation-
      substitution, innovation, and transformation. Soon everyone will recognize the
      fundamental changes online health has produced in the way we think and act about
      health care. A NEW ACADEMIC SUBSPECIALTY: A new subspecialty--consumer health
      informatics (CHI)--is covering two domains: (1) community CHI resources--the
      online networks, forums, databases, and World Wide Web sites that anyone with a
      home computer can access, and (2) clinical CHI resources--programs or systems
      developed by clinicians, system developers, or health maintenance organizations
      and provided to selected membership groups or patients. EXHIBITS: Sample
      communications among online self-helpers within their chat groups, e-mail
      exchanges, bulletin boards, and USENET newsgroups for chosen health topics show
      what is on their mind, how they get information, how they use it, and how they
      correct it. Sometimes, clinicians have observed, lay care offers higher quality
      than professional care. Lay self-helpers, such as the originator of the Brain
      Tumor Mailing List, have observed several potential benefits in linking online
      self-helpers and providers and at a very modest cost. FUTURE DIRECTIONS: In a
      coming six-level system of information-age health care, patient-consumers may
      seek what they need in the following order: individual self-care, family and
      friends, informal self-help networks, the professional as coach, the professional
      as partner, and the professional as authority.

PMID- 9179718
TI  - How will we know if we got it right? Aims, benefits, and risks of consumer
      information initiatives.
AB  - BACKGROUND: Initiatives on the part of many groups to provide American consumers
      with information about the quality of health care may have several goals.
      Symbolic aims include recognizing consumers, increasing the sense of
      accountability, providing reassurance about health care quality, and emphasizing
      quality. Instrumental aims include improving system performance, increasing
      satisfaction with care and/or plans, and reducing random plan switching. These
      efforts may have both good effects and bad effects. BENEFITS AND RISKS: The
      possible positive byproducts of consumer information initiatives are learning
      about consumer preferences and variations, learning how to help consumers use
      health plans and providers, changing consumer-provider relationships, and
      building an infrastructure of consumer-centered intermediaries. Possible bad
      effects are generating demands that cannot be met, skewing the system to certain
      consumers' preferences, discouraging consumers from using information, adding
      another new program that will die, contributing to biased plan selection, and
      decreasing trust in providers. DISCUSSION: Before health care professionals can
      gather evidence about outcomes signaling success, they must address several major
      issues. How should high-quality performance be defined and by whom? Whose vision
      will be embedded in these definitions? Will it be the consumer's vision or the
      patient's vision that will be maximized? How long will it take before expected
      consequences occur? A strategy to measure success calls for beginning immediately
      to develop consensus on outcomes and a "theory of action" specifying the pathways
      and timing for different players.

PMID- 9179719
TI  - Measuring and averting underuse of necessary cardiac procedures: a summary of
      results and future directions.
AB  - BACKGROUND: Attempting to explain the marked variation in utilization of medical
      procedures has vexed health policy analysts for nearly three decades. Most health
      services research to date has been directed at identifying and reducing excessive
      utilization. Little attention has been given to underuse of care. THE LOS ANGELES
      CARDIAC UNDERUSE PROJECT OVERVIEW: A research group at the University of
      California, Los Angeles (UCLA), performed two separate, published studies seeking
      to measure underuse of coronary angiography and coronary artery revascu
      larization (bypass surgery and angioplasty), two critical links in the chain of
      care leading from initial diagnosis of coronary artery disease to definitive
      treatment. In each study, the necessity criteria developed by the panel were used
      to identify patients needing an invasive procedure. RESULTS: Within this
      population of patients (sampled predominantly from public hospitals), substantial
      underuse of clinically necessary coronary angiography (41% without refusers) and
      revascularization (23% without refusers) was detected. In this select population
      of patients, receiving a necessary revascularization procedure appeared to both
      reduce the risk of death and improve quality of life. DISCUSSION: Despite
      limitations of the method, detection of underuse is feasible, valid, and
      affordable in the context of overall health care expenditures. Moreover, the case
      for implementing "underuse prevention" systems is increasingly compelling.
      Measuring and disseminating data on underuse of expensive but highly beneficial
      procedures would provide health care consumers (patients and employers) with
      useful information and enable health care providers to develop quality
      improvement strategies aimed at rational use of health care resources.

PMID- 9179720
TI  - The Institute of Medicine's Special Initiative on Health Care Quality: an
      interview with Molla Donaldson. Interview by Steven Berman.

PMID- 9179721
TI  - Methyl tertiary-butyl ether (MTBE): use as an oxygenate in fuels.

PMID- 9179722
TI  - Pharmacokinetics and disposition of methyl t-butyl ether in Fischer-344 rats.
AB  - Methyl t-butyl ether (MTBE) is a commonly used octane booster in gasoline. This
      study examines the pharmacokinetics and disposition of MTBE in Fischer-344 rats
      after i.v., oral, dermal and inhalation routes of administration. Groups of male
      and female rats were given single i.v. (40 mg kg-1), oral (40 and 400 mg kg-1)
      and dermal (40 and 400 mg kg-1 in occluded chambers) doses of [14C]MTBE. For
      inhalation studies, rats were exposed nose-only for 6 h to low (400 ppm), high
      (8000 ppm) and repeated daily 6-h low (400 ppm x 15 days) chamber concentrations
      of [14C]MTBE. Blood, expired air, and excreta (urine and feces) were collected at
      selected times up to 7 days post-dose and quantified for 14C content. Plasma
      concentrations of MTBE and t-butyl alcohol (TBA) were quantified and mean values
      used for pharmacokinetic analysis. The mean total recoveries of 14C ranged from
      91 to 105%. Methyl t-butyl ether was rapidly and completely absorbed after oral
      and inhalation exposures; dermal absorption was low. After all routes, MTBE was
      rapidly eliminated from blood (ti = 0.5 h) by exhalation and metabolism to TBA.
      At the high doses, metabolism was saturated and the proportion of renal 14C
      excretion decreased relative to the pulmonary route. At 48 h post-exposure,
      virtually all of the 14C was eliminated. The major metabolites recovered in urine
      were 2-methyl-1,2-propanediol and alpha-hydroxyisobutyric acid. There were no
      significant gender or route-dependent differences in the pharmacokinetics and
      disposition of MTBE.

PMID- 9179723
TI  - Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE)
      in rats.
AB  - A two-generation reproductive toxicity study of methyl tertiary-butyl ether
      (MTBE) was conducted in Sprague-Dawley rats. Twenty-five rats of each sex (F0)
      were exposed by inhalation to 0, 400, 3000 or 8000 ppm MTBE vapor, 6 h a day for
      10 weeks prior to mating. Parental animals were then mated within groups for up
      to 3 weeks. Parental females were exposed during mating, gestation and lactation
      (starting on day 5); parental males were exposed during mating through delivery
      of their last litter sired. The F1 adults were selected from the F1 litters and
      were exposed beginning on postnatal day 28 for at least 8 weeks before mating to
      produce F2 litters. During exposures to 3000 and 8000 ppm MTBE, group
      observations included hypoactivity and lack of startle reflex in parental animals
      from both generations. Parental animals at 8000 ppm were also ataxic. During the
      pre-mating period, body weights of the 8000 ppm males from both generations and
      the F1 females were significantly reduced compared to control animals. Transient
      body weight reduction was also observed in the 3000 ppm F1 males and females
      during the pre-mating period. Lactational body weights were increased in the 8000
      ppm females from both generations. In the F1 generation, increased liver weights
      were noted in the 3000 and 8000 ppm animals for both sexes, although
      histopathological examination revealed no treatment-related effects. There were
      no treatment-related reproductive effects noted in any of the parameters measured
      in this study. Offspring survival was equivalent among treated and control groups
      from both generations, and there were no remarkable post-mortem findings. There
      was, however, a significant increase in dead F2 pups in the 8000 ppm group on
      postnatal day 4. The F1 litters at 3000 and 8000 ppm had lowered body weights
      from postnatal days 14-21 and 14-28, respectively. The F2 generation of pups at
      3000 and 8000 ppm also exhibited lowered body weights from postnatal days 14-28
      and 7-28, respectively. Body weight gains in both the F1 and F2 litters were also
      reduced for the corresponding time intervals. Thus, exposure to MTBE vapor
      produced no reproductive toxicity to two generations of Sprague-Dawley rats even
      in the presence of parental toxicity at 3000 and 8000 ppm. Postnatal toxicity was
      observed in the offspring of both generations, but only in the presence of
      maternal toxicity. The no-observed-effect level (NOEL) for both parental and
      postnatal toxicity is 400 ppm, and the NOEL for reproductive toxicity is at least
      8000 ppm.

PMID- 9179724
TI  - Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by
      inhalation in mice and rabbits.
AB  - Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per
      group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary
      butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6
      18, respectively. Maternal body weights, clinical observations and food
      consumption were recorded throughout gestation for both species. At scheduled
      euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed
      and examined for external, visceral (including craniofacial) and skeletal
      alterations. For both species, the pregnancy rate was high and equivalent across
      all groups; no pregnant animals died or aborted. There were no does that
      delivered early, but there were three mouse dams in the control group and two
      dams in the 4000 ppm group that delivered early and were removed from the study.
      In mice, maternal body weights, body weight gain, corrected maternal gestational
      weight change and food consumption were significantly reduced in mice at 8000
      ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm.
      Gestational parameters affected at 8000 ppm included post-implantation loss (due
      to increased late resorptions and dead fetuses) and altered sex ratio (decreased
      males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There
      was a significantly increased incidence of cleft palate at 8000 ppm; this
      resulted in increased incidences of pooled external and visceral malformations
      and of total malformations at this exposure concentration. There were also
      treatment-related increases in the incidence of individual skeletal variations at
      4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were
      significantly reduced at 4000 and 8000 ppm. Relative liver weights were also
      reduced at 8000 ppm. All gestational parameters were equivalent across all
      groups, including pre- and post-implantation loss, fetal sex ratios, litter size
      and fetal weights/litter. There was no evidence of treatment-related
      teratogenicity observed at any dose tested in rabbits. The no-observed-effect
      levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice
      and 1000 ppm and at least 8000 ppm, respectively, in rabbits.

PMID- 9179725
TI  - Assessment of the in vivo mutagenic potential of methyl tertiary-butyl ether.
AB  - Methyl tertiary-butyl ether (MTBE) is one of the highest production volume
      chemicals in the USA. Previous results from in vitro genetic toxicity studies
      suggested that it was not mutagenic. However, chronic exposure at high levels
      resulted in liver tumors in female mice and kidney tumors in male rats. The
      current program assessed in vivo genotoxicity and also explored the possibility
      that a mutagenic mechanism was involved in the carcinogenic process. The specific
      tests used included the Drosophila sex-linked-recessive-lethal test, the rat bone
      marrow cytogenetics test, the mouse bone marrow micronucleus test and the in vivo
      in vitro hepatocyte unscheduled DNA synthesis test in the mouse. All tests
      produced negative results, indicating that the potential for in vivo mutagenic
      activity was low. These data also suggest that the tumorigenic activity was
      probably the result of a non-genotoxic process.

PMID- 9179726
TI  - Evaluation of 13-week inhalation toxicity study on methyl t-butyl ether (MTBE) in
      Fischer 344 rats.
AB  - Methyl-t-butyl ether (MTBE) is widely used as an octane enhancing agent in
      gasoline. A 13-week inhalation study was conducted in Fischer 344 rats to provide
      information on potential target organs and toxicity of MTBE, and to ascertain a
      no-observed-adverse-effect level (NOAEL) for MTBE. Male and female Fischer 344
      rats were exposed to target doses of MTBE vapor of 0, 800, 4000 and 8000 ppm for
      6 h a day, 5 days per week for 13 weeks: MTBE produced no mortalities. At 8000
      ppm, males and females showed a decrease in body weights compared to controls.
      The only notable effect on clinical observation was ataxia at 8000 ppm, which was
      apparent during the first 4 weeks of treatment. Mild hematological and clinical
      chemistry changes were observed in the 8000 ppm group. At 8000 ppm, animals
      showed increased serum levels of corticosteroids, which suggest some stress-like
      effect. At necropsy, there were no treatment-related gross lesions. Absolute and
      relative organ weights (liver, adrenals and kidneys) were increased in both sexes
      at 4000 and 8000 ppm, but there were no microscopic lesions in these tissues with
      the exception of the kidney. Microscopic examination of other tissues revealed no
      effects with the exception that at 8000 ppm, male rats showed: mild increased
      size of hyaline droplets within the kidney, mild increase in hemosiderosis in the
      spleen and higher incidence of hyperplasia in the lymph nodes. The highest NOAEL
      was judged at 800 ppm.

PMID- 9179727
TI  - Oncogenicity studies of inhaled methyl tertiary-butyl ether (MTBE) in CD-1 mice
      and F-344 rats.
AB  - Oncogenicity studies of methyl tertiary-butyl ether (MTBE) vapor were conducted
      in CD-1 mice and Fischer 344 rats. Fifty animals of each sex per species per
      group were exposed for 6 h a day, 5 days per week to 0 (control), 400, 3000 and
      8000 ppm MTBE vapor in air for 18 months (mice) and 24 months (rats). Both
      species showed reversible central nervous system depression at 8000 ppm for the
      first week of exposure, which continued for mice for the study duration. For the
      8000 ppm mice, reduced body weight gain and early mortality prior to terminal
      euthanasia were exposure related. In the males, these deaths appear to be due to
      exacerbation of uropathy or dysuria, which occurs spontaneously in this strain.
      Increases in absolute and relative liver (both sexes) and kidney weight (males
      only) were seen at 3000 and 8000 ppm and decreases in brain and spleen weights
      were also noted (the latter decreases were without microscopic lesions and
      occurred at 8000 ppm only). An increase in hepatocellular hypertrophy occurred in
      both sexes at the two highest concentrations. The only neoplastic lesion found in
      this study in mice was an increased incidence of hepatocellular adenomas in
      females at the 8000 ppm exposure. In a follow-up study, a statistically
      significant elevation of cell proliferation in female mouse liver has been shown
      to occur following 5 days, but not 28 days, of exposure to 8000 ppm MTBE,
      suggesting that MTBE induces mitogenesis. For male rats, early euthanasia was
      required at week 82 and week 97 for the 8000 and 3000 ppm groups, respectively,
      due to excessive mortality from a severe progressive nephrosis. The end stage of
      this process appeared earlier in the male rats of all MTBE exposure groups; the
      incidence of this lesion and mortality for exposed females was comparable to
      control females. No exposure-related changes in hematological parameters were
      observed for any group at any time point, but a decrease in corticosterone levels
      was seen for male rats from the 8000 ppm group. Absolute and relative kidney and
      liver weight increases occurred in 3000 and 8000 ppm exposure groups, but the
      liver weight change was not accompanied by histopathological change. At study
      termination, increases in the incidence and severity of a chronic nephropathy in
      males from all exposure groups and in females exposed to 3000 and 8000 ppm was
      associated with secondary lesions of hyperplasia of the parathyroid and
      mineralization of tissues. Renal tubular cell tumors were increased in male rats
      exposed to 3000 and 8000 ppm. This may be associated with an accumulation of
      protein (stainable by Mallory's Heidenhain) in kidney tubular epithelial cells
      after 4 weeks of exposure. An increased incidence of interstitial cell adenomas
      of the testes was seen in males exposed to 3000 and 8000 ppm but was believed to
      be an artefact of an unusually low control incidence and not considered to be
      exposure related. Based on the above effects, the no-observed-effect level (NOEL)
      for chronic toxicity is 400 ppm, and the NOEL for carcinogenic effects is 3000
      ppm (mice) and 400 ppm (rats).

PMID- 9179729
TI  - Virtual reality and gastrointestinal endoscopy, or, is Virtual Vision a speed
      bump on the road to telepresence?

PMID- 9179728
TI  - Neurotoxicological evaluation of methyl tertiary-butyl ether in rats.
AB  - Methyl tertiary-butyl ether (MTBE) is an oxygenate that is added to gasoline to
      boost octane and enhance combustion, thereby reducing carbon monoxide and
      hydrocarbon tailpipe emissions. The acute and subchronic neurotoxicity of MTBE
      were evaluated in rats using a functional observation battery (FOB), measures of
      motor activity (MA) and a neuropathological evaluation. In the acute study, rats
      were exposed once to 0, 800, 4000 or 8000 ppm MTBE by inhalation for 6 h and then
      evaluated three times over a 24-h period. In the FOB evaluations, treatment
      related effects were seen at the 1-h session immediately following exposure and
      were indicative of transient central nervous system (CNS) depression. Effects
      were most apparent in the high-dose group (8000 ppm) but were also evident to a
      lesser extent in the mid-dose (4000 ppm) group. Labored respiration, ataxia, duck
      walk gait and decreases in muscle tone, hind-limb grip strength and treadmill
      performance were the most frequently noted findings. No significant effects were
      observed in the FOB when testing was conducted at 6 h and 24 h post-exposure. The
      pattern of motor activity measured in the different dose groups following
      exposure was also in keeping with a reversible CNS-depressant effect of MTBE. In
      the subchronic study, rats were exposed to 0, 800, 4000 or 8000 ppm MTBE for 6 h
      a day, 5 days per week, for 13 weeks. No persistent or cumulative effects on
      neurobehavioral function were found. Body weights and absolute brain weights were
      reduced in the 8000 ppm group, however there were no differences among groups
      when brain weight was expressed relative to body weight. No histopathological
      changes were noted in the brains or peripheral nervous tissues of MTBE-exposed
      animals. In summary, MTBE produced signs of acute reversible CNS depression
      following exposure to 8000 ppm and, to a lesser extent, to 4000 ppm vapor. The no
      observed-adverse-effect level for these effects was 800 ppm in the present study.
      No persistent or cumulative neurotoxic effects were observed following exposure
      to MTBE at concentrations up to 8000 ppm for 13 weeks.

PMID- 9179730
TI  - Oxides, onions, and other matters gastrointestinal--1996--a perspective.
AB  - A selection of landmark articles for a given year in any subject risks being
      somewhat subjective, and subjectivity is best avoided in scientific endeavor.
      However, the very nature of such a selection process invites judgment. Like most
      judges, I, too, claim to avoid conscious bias, but no one who has ever graced the
      bench can claim that at the subconscious level personal bias has never crept into
      a decision. Similarly, deep down in the vault of my subconscious, I love a
      maverick. That perhaps explains why so many articles that challenge long-held
      beliefs have especially found favor. Among them are those that question the
      strength of the association of Helicobacter pylori with gastric cancer, the
      usefulness of surveillance endoscopy in patients with Barrett's esophagus, a
      randomized trial that casts doubt on the preeminence of laparoscopic
      cholecystectomy, and a metaanalysis that concludes that corticosteroids may not
      be nearly as good for alcoholic hepatitis as we were once told. I have tried to
      resist the temptation to be too laudatory of technologic advancement, unless the
      benefit to the patient of such technology has been defined clearly. Thus, of all
      of the new technologies (endoscopic retrograde choledochopancreatography is no
      longer a new technology), only endoscopic ultrasonography finds a place. Articles
      that assess preventive strategies and are in the realm of epidemiology have
      received mention. All in all, 1996 was not a spectacular year for major
      therapeutic advances. In contrast, some notable advances have been made in the
      laboratory, and perhaps the most important has to do with the role of nitric
      oxide both in the regulation of normal function and in the genesis of disease.

PMID- 9179731
TI  - Psychological predictors of peptic ulcer incidence in the Alameda County Study.
AB  - It has often been suggested that mood and personality predispose to peptic ulcer,
      but little prospective evidence exists. We used longitudinal data from the
      Alameda County Study to seek associations of psychological characteristics with
      later ulcer development, taking into account the possible confounding or
      mediating, taking into account the possible confounding or mediating roles of
      nonpsychological factors. Among 4,595 Alameda County Study subjects ulcer-free in
      1965, we studied five baseline psychological measures (depression, hostility, ego
      resiliency, social alienation or anomy, and personal uncertainty) with respect to
      reported ulcer in 1973-1974. All five measures had significant age-adjusted
      associations with incident ulcer [odds ratio (O.R.) 1.8-2.6]. After adjustment
      for smoking, drinking, skipping breakfast, lack of sleep, painful medical
      conditions, and liver disease, three measures remained significant: depression,
      anomy, and hostility. The age-adjusted O.R. of 2.8 [95% confidence interval
      (C.I.) 1.6, 4.8] for an upper versus a lower tertile index of independently
      predictive psychological factors fell to 2.1 with adjustment for health-related
      behaviors and medical conditions, and reached 1.7 (C.I. 1.0, 3.1) after addition
      of education to the model. We conclude that depression, maladjustment, and
      hostility are prospectively associated with peptic ulcer. These associations are
      partially accounted for by confounding or mediation by standard risk factors, and
      are to some extent related to socioeconomic status.

PMID- 9179732
TI  - Yield of routine endoscopy beyond the duodenal bulb.
AB  - The authors determined the clinical yield, endoscopic time, and patient tolerance
      of routine upper endoscopy beyond the duodenal bulb. From May through October
      1994, all patients undergoing routine esophagogastroduodenoscopy (EGD) were
      recruited for study. Each procedure was timed from start to finish by the
      endoscopy nurse, and, in addition, the time of the postbulbar examination was
      recorded. The endoscopy nurse assessed the patient's comfort level when the
      endoscope was advanced into the duodenal bulb and again at the postbulbar region.
      A total of 250 EGDs were performed. There were 152 males and 98 females, with a
      mean age of 57.1 (range, 23-91) years. Indications for the procedure were as
      follows: gastroesophageal reflux disease symptoms 82, epigastric pain 64,
      dysphagia 46, Barrett's surveillance 25, anemia 23, other research study 16, and
      other 61. The mean time for the procedure was 11 min and 54 s, whereas the mean
      time for the postbulbar examination was 46.6 s. Patients tolerated endoscope
      insertion well both before and during examination of the postbulbar duodenum. The
      only postbulbar finding that affected clinical management was a postbulbar ulcer
      in a patient without other ulcers who was positive for Helicobacter pylori.
      Although routine endoscopic examination beyond the duodenal bulb involves minimal
      time and is well tolerated by patients, the yield of pathologic findings is low
      (3.6%) and the yield of findings that alter clinical management even lower
      (0.4%). In patients without prior GI surgery undergoing routine EGD for
      indications other than suspected small bowel pathology or active upper GI
      bleeding, examination of the postbulbar duodenum can be considered an elective
      part of the procedure.

PMID- 9179734
TI  - Risk factors for fecal incontinence in a nursing home population.
AB  - Even though fecal incontinence is a leading cause of nursing home placement, risk
      factors contributing to its development have not been established. Identification
      of such factors may lead to prevention of incontinence and reduce the need for
      nursing home placement. A total of 388 residents of five nursing homes were
      included. Data regarding mental status, bowel habits, obstetrics history, and the
      presence, frequency, and severity of fecal incontinence were collected for each
      participant. Of the 388 nursing home residents, 46% were incontinent of feces.
      Incontinence was 1.5 times more common in males and in those younger than 65
      years of age. In both univariate and multivariate analyses, diarrhea, dementia,
      restricted mobility, and male gender were independently associated with
      incontinence. In contrast to previous studies, constipation was not associated
      with fecal incontinence. If elimination of these risk factors leads to prevention
      of incontinence in even a few people, some elderly patients may not require
      institutionalization, which will result in improvement in their quality of life,
      not to mention a reduction in public health expenditures.

PMID- 9179733
TI  - Clinicopathologic features of submucosal carcinoma of the stomach.
AB  - A retrospective study of 155 patients with submucosal gastric carcinoma compared
      the clinicopathologic features with mucosal and muscularis proprial gastric
      carcinoma. Fifty-seven percent of the patients presented with gastrointestinal
      symptoms, whereas 36.1% had been detected by mass screening. The incidence of
      curative resection, lymph node metastasis, and complications were 96.1, 20.6, and
      14.8%, respectively. Two patients died of sepsis and pulmonary infarction 30 days
      post-operatively. Five patients died of recurrent gastric cancer 1-5 years
      postresection. The overall 5-year survival rate was 90.2%. Recurrence patterns,
      histologic type, lymph node metastasis, lymphatic and venous infiltration, and
      growth pattern were similar to those of muscularis proprial carcinoma rather than
      mucosal carcinoma. Therefore, curative gastrectomy with extended lymphadenectomy
      (D2) may be feasible for submucosal carcinoma of the stomach.

PMID- 9179736
TI  - Fatal diffuse invasive gastrointestinal candidiasis masking as ileus after bone
      marrow transplantation.
AB  - High-dose cytotoxic chemotherapy has increased the incidence of candidal
      infections that make neutropenic patients very sick and may kill them. We report
      fatal invasive candidiasis involving the entire alimentary tract after autologous
      bone marrow transplantation in a young woman with breast cancer. Illustrated are
      the significance of fungal infections in this patient population, the potential
      for Candida albicans to invade the entire gastrointestinal tract, and the
      potential role of endoscopy in the early diagnosis of these often catastrophic
      infections. We also suggest that diffuse, invasive candidiasis should be
      considered in the differential diagnosis of ileus in the immunocompromised
      patient.

PMID- 9179735
TI  - Endoscopic injection sclerotherapy with 1.5% Sotradecol for bleeding cardiac
      varices.
AB  - The authors retrospectively studied the efficacy of endoscopic injection
      sclerotherapy (EIS) with 1.5% Sotradecol (STD) in patients with bleeding cardiac
      varices (CV). Case histories of 27 patients with large, isolated, bleeding CVs
      were reviewed. Case records of another 27 patients with isolated esophageal
      varices (EV), matched for age, sex, and year EIS was performed, were selected
      from a computer data bank as controls. Using a small volume (2-4 ml) of injection
      per vessel, the rate of immediate control of bleeding was 66.7% (18 of 27) in the
      CV group and 70.4% (19 of 27) in the EV group. The early rebleeding rate was
      higher for patients in the EV group (48.1%, 13 of 27) than for those in the CV
      group (18.5%, 5 of 27) (p = 0.0209). On the other hand, it was more difficult to
      control the rebleeding from CV (p = 0.00494). In terms of mortality, there was no
      statistically significant difference between the CV and EV groups (33.3 versus
      29.6%) within 1 week after EIS, but the 1-month post-EIS mortality rate was
      significantly higher (p = 0.0278) in the CV group (18 of 27, 66.7%) than in the
      EV group (10 of 27, 37.0%). Among those in the CV group who died of late
      complications within 1 month after EIS, three died of recurrent hemorrhage, five
      of infection, and one of viscus perforation. In the EV group, only two patients
      died of infection. Thus, it was concluded that EIS with small volumes (2-4 ml) of
      1.5% STD was equally effective in controlling immediate bleeding from CV and EV.
      However, it was more difficult to control early rebleeding from CV, and the
      mortality and complications within 1 month after EIS were significantly higher in
      patients with CV. These observations are currently under careful study and
      evaluation.

PMID- 9179737
TI  - Three-dimensional helical computed tomography with intravenous cholangiography
      for sclerosing cholangitis manifested as postcholecystectomy symptom.
AB  - A 46-year-old woman who had upper abdominal pain 10 years after cholecystectomy,
      and who had incidental sclerosing cholangitis (SC), was investigated by three
      dimensional helical computed tomographic (3-DHCT) cholangiography with contrast
      medium, because endoscopic retrograde cholangiography (ERC) was unsuccessful and
      a second ERC was not permitted by the patient. The cholangiogram demonstrated
      annular strictures of the bilateral hepatic duct at the confluence of the common
      hepatic duct, and dilatation of the left intrahepatic biliary duct. Although we
      could not clarify the cause of the biliary tract deformity at the time of the 3
      DHCT, the tentative diagnosis of postcholecystectomy deformity of the biliary
      tree led to successful treatment by right liver lobectomy and
      hepaticojejunostomy. Histologic findings were compatible with SC. From this
      experience and the literature, we suggest that 3-DHCT cholangiography with
      contrast medium can contribute to the preoperative diagnosis of morphological
      changes in the biliary tree in patients with postcholecystectomy symptoms.

PMID- 9179738
TI  - Primary systemic amyloidosis with giant hepatomegaly and a swiftly progressive
      course.
AB  - Although the involvement of the liver is common in systemic amyloidosis (AL),
      clinical features of hepatic dysfunction and liver chemistry abnormalities are
      often mild or absent. A mild increase in the serum alkaline phosphatase value is
      the most common finding. Hypertransaminasemia, hyperbilirubinemia, and portal
      hypertension with ascites and gastroesophageal varices occur late in the course
      of the disease and predict a short survival. We describe the case of a 58-year
      old woman with AL, whose dramatic and unusual clinical picture, consisting of
      giant hepatomegaly, hypertransaminasemia, increase in alkaline phosphatase,
      esophageal varices, and ascites, was rapidly complicated by severe obstructive
      cholestasis.

PMID- 9179739
TI  - Candida (Torulopsis glabrata) liver abscesses eight years after orthotopic liver
      transplantation.
AB  - The authors report the case of a 48-year-old man in whom candida (Torulopsis
      glabrata) liver abscesses developed 8 years after liver transplantation. After a
      week of fever, computed tomography and Doppler ultrasonography showed several
      fluid-filled loculations in the left lobe of the liver and hepatic arterial
      stenosis. Aspirates from the abscesses contained T. glabrata organisms. This
      complication probably developed because hepatic arterial stenosis resulted in
      bile infarcts (bilomas), which were contaminated via the biliary tract with
      candida from the biliary-enteric anastomosis. Catheter drainage and
      administration of amphotericin B for 10 weeks permitted successful
      retransplantation. T. glabrata liver abscesses, a life threatening complication
      that can occur long after liver transplantation, can be successfully managed by
      aggressive medical treatment followed by retransplantation.

PMID- 9179740
TI  - Liver tests in hyperthyroidism: effect of antithyroid therapy.
AB  - Changes in liver biochemical test results have been described in hyperthyroid
      patients before and after antithyroid therapy. In the present study, we analyzed
      liver tests at diagnosis and after 6 weeks of treatment with propylthiouracil
      (PTU) in 43 patients with hyperthyroidism. At diagnosis, 60.5% of the patients
      had at least one liver abnormality. Elevations of alkaline phosphatase, alanine
      and aspartate aminotransferase, and gamma-glutamyl transpeptidase levels were
      observed in 19 (44.2%), 10 (23.3%), six (14%), and six (14%) of the patients,
      respectively. At the end of the 6-week treatment with PTU, elevations in liver
      test values, possibly induced by PTU, were found in seven (16.3%) patients. Age,
      sex, type of goiter (either diffuse or multinodular), and presence or absence of
      abnormal liver biochemical tests at diagnosis were not significant in determining
      the possibility of PTU-induced elevations in liver tests. These data suggest that
      liver test abnormalities are frequently found at the time of diagnosis of
      hyperthyroidism. However, the presence or absence of these abnormalities does not
      predict elevations in liver test results, which are possibly induced by PTU
      during therapy.

PMID- 9179741
TI  - Barrett's adenocarcinoma in a patient with acquired immune deficiency syndrome.

PMID- 9179742
TI  - Lymphangioma of the small-bowel mesentery: unusual cause of intestinal
      obstruction.

PMID- 9179743
TI  - Colosalpingeal fistula: a rare complication of diverticular disease of the colon.

PMID- 9179744
TI  - Primary liver gastrinoma.

PMID- 9179746
TI  - Histological changes caused by the rc mutation in chickens.
AB  - The rc gene represents a recessive mutation in chickens, known to cause retinal
      degeneration and blindness, as well as abnormal sarcolemmal membranes of cardiac
      myocytes associated with reduced choline transport. In this study, the visceral
      organs from "old" (aged 12 months) and "young" (aged 5 months) homozygous blind
      (rc/rc), heterozygous (Rc+/rc) and normal (Rc+/Rc+) chickens were examined
      histologically to investigate whether the primary effect of the mutation was on
      cellular structure. Homozygous birds showed enlarged thyroids with acidophilic
      colloids in enlarged and often ruptured follicles, macrovesicular lipid
      accumulation in the liver, increased numbers of nuclei in the myocardial fibres,
      hypertrophy of the lobular structure of the medullary portion of the thymus,
      cloudy swelling of the tubular epithelium of the kidney and slow maturation (in
      young birds) and degeneration (in old birds) of the gonads. All lesions, except
      for those of the thymus, were more severe in old than in young birds. Some
      heterozygous chickens were mildly affected and none of the normal (Rc+/Rc+) birds
      exhibited these abnormalities.

PMID- 9179745
TI  - Hyperphosphatemic hypocalcemic coma caused by hypertonic sodium phosphate (fleet)
      enema intoxication.

PMID- 9179747
TI  - Feline immunodeficiency virus (FIV) infection in cats at necropsy: a serological
      study.
AB  - Sera collected post mortem during a 6-month period from cats were tested for
      feline immunodeficiency virus (FIV)-specific antibodies by (1) an enzyme-linked
      immunosorbent assay (ELISA), (2) an indirect peroxidase-based immunocytological
      test (IP), (3) a Western immunoblotting (WB) method with FIV-infected cell
      lysates, and (4) a WB method with purified viral antigen. All four methods were
      capable of detecting FIV-specific antibodies in haemolysed sera. However, the
      ELISA showed the lowest "positive predictive value" (PVpos = 22%) followed by the
      IP (PVpos 50-60%). Serum was FIV antibody-positive in 6% (15/255) of all cats
      examined. The mean age of seropositive cats was 9 years (4 years among
      seronegative cases) and the male-to-female ratio in such cats was 1.8 to 1
      (overall ratio 0.8 to 1). Forty per cent of the seropositive cats were in the
      final phase of acquired immune deficiency syndrome. Feline leukaemia virus (FeLV)
      predominated among viral co-infections. It was concluded that (1) a combination
      of the IP and WB reliably detected FIV-specific antibodies in sera collected post
      mortem, and (2) at post-mortem examination, cats from high-risk groups (male, > 5
      years old, hypercellular bone marrow) were frequently infected with FIV.

PMID- 9179748
TI  - Vitamin (A and D)-induced premature physeal closure (hyena disease) in calves.
AB  - Hypervitaminosis A and D is a potential cause of "hyena disease" in cattle, which
      results from premature growth-plate closure in long bones of calves. This study
      showed that vitamin A induced growth-plate closure if calves were given an
      intramuscular injection of vitamins A and D (2,000,000 IU and 300,000 IU,
      respectively) on the first day after birth and, in addition, vitamin A (30,000
      IU/kg body weight) in a water dispersible form was added to the milk substitute
      daily. Gross lesions were observed in the proximal tibial growth plates of each
      of seven calves after 3 weeks of vitamin-A treatment. Microscopical examination
      showed commencing premature growth-plate closure in the proximal tibia at 2
      weeks. After one week, the growth plate showed focal thinning, and there was
      premature endochondral ossification of columnar cartilage. Longitudinal bone
      growth was dramatically reduced before growth plate closure at one week (25
      microns/day in a treated animal versus 136 microns/day in a control). Liver
      concentrations of retinol and retinyl palmitate became strikingly elevated at on
      week, and thereafter increased slowly until the third week. Elevation of plasma
      retinol and retinyl palmitate was rapid, reaching a maximum on day 10. Plasma all
      trans-retinoic acid was undetectable in many samples from treated animals, but
      plasma concentrations of derivatives of retinoic acid (9-cis-retinoic acid, 13
      cis-retinoic acid, 13-cis-4-oxoretinoic acid, and 9, 13 dicis-retinoic acid) were
      elevated. The vitamin-A intake required to induce growth-plate closure in calves
      was found to be exceedingly high. Vitamin-A toxicity must be considered as a
      potential cause of hyena disease, but it would seem likely that other factors
      also play a role.

PMID- 9179749
TI  - Morphological evidence of apoptosis in chickens infected with infectious bursal
      disease virus.
AB  - Two-week-old specific pathogen-free chickens were infected with the infectious
      bursal disease virus by the ocular route. Immediately, and at 4 and 8 days after
      infection, groups of three chickens were killed and tissue samples were
      collected. Under electron microscopical examination, typical apoptotic cells were
      seen in the bursa of Fabricius (BF) and in the spleen. Tissue sections stained
      with haematoxylin and eosin were subjected to image analysis to quantify cellular
      depletion in the follicles of the BF. Unstained sections were treated with a
      terminal deoxy-transferase-based kit to detect apoptotic cells. The numbers of
      apoptotic cells at different stages of infection were counted by image analysis.
      The results revealed a rapid depletion of cells in the BF and a simultaneous
      increase in apoptotic cells.

PMID- 9179750
TI  - Cardio-histopathological observations on aborted equine fetuses infected with
      equid herpesvirus 1 (EHV-1).
AB  - Twenty-five aborted equine fetuses infected with equid herpesvirus 1 (EHV-1) were
      examined cardio-histopathologically. The main changes in the heart consisted of
      interstitial myocarditis and intramyocardial vascular lesions accompanied by
      degeneration and necrosis of the cardiac myocytes. Vascular pathology of
      intramyocardial small arteries and arterioles was characterized by endothelial
      cell necrosis and fibrinoid changes in the media. Eosinophilic intranuclear
      inclusion bodies characteristic of herpesvirus infection were detected in the
      myocardial cells and macrophages within and around the inflammatory lesions and
      in the endothelial cells and medial smooth muscle cells of the damaged vessels.
      This observation, taken in conjunction with the fact that EHV-1 antigens were
      detected immunohistochemically in some myocardial and endothelial cells, provides
      morphological evidence in support of the viral aetiology of the cardiac lesions.

PMID- 9179751
TI  - Immunohistochemical demonstration of the spread of pneumotropic strain 4892 of
      Aujeszky's disease virus in conventional pigs.
AB  - Sixteen pigs aged 5 to 7 weeks were inoculated intranasally with the pneumotropic
      strain 4892 of Aujeszky's disease virus (ADV) in a dose of 2 x 10(5) TCID50. Pigs
      died or were killed on day 4, 5, 6, 7, 8, 10, 12, 20 or 30 post-inoculation (PI).
      Two further pigs were kept as negative (uninfected) controls. Histopathological
      examination demonstrated meningoencephalitis, necrotizing rhinitis and multifocal
      systemic necrosis. Viral antigen was detected immunohistochemically, mainly in
      the central nervous system up to day 12 PI, and to a lesser degree in the lung,
      nasal mucosa and tonsil. ADV DNA was detected at days 20 and 30 PI by a nested
      polymerase chain reaction technique. This study indicated that the spread of the
      highly virulent, pneumotropic strain 4892 did not differ from that of other
      neurotropic or pneumotropic ADV strains.

PMID- 9179752
TI  - Squamous cell carcinoma of the renal pelvis with metastasis in a dog.
AB  - The gross and microscopical features of a squamous cell carcinoma of the renal
      pelvis in an 18-year-old dog are described. This is a rare tumour originating
      from transitional cells of the pelvis. The tumour, which invaded the renal
      parenchyma and capsule and the small intestinal wall, metastasized to the lungs.
      Tumour cells expressed cytokeratin 8 and were arranged in a pattern similar to
      that of a squamous cell carcinoma found elsewhere, with prickle cells and horny
      pearls. The tumour was not diagnosed clinically but was found at necropsy. The
      presence of pelvic calculi in this dog is suggested as a cause of transitional
      cell squamous metaplasia and malignant transformation.

PMID- 9179753
TI  - Histopathological features of canine distemper recently observed in Japan.
AB  - Eleven dogs with canine distemper (CD) from the Chubu region of Japan and the
      Tokyo area were examined. Clinically, respiratory and neurological signs were
      present in all animals. Histopathologically, all showed characteristic CD lesions
      of bronchopneumonia and demyelinating encephalitis. However, some differences in
      gastrointestinal abnormalities were observed. Three out of four dogs from the
      Chubu region had severe diarrhoea and gastroenteritis, associated with numerous
      eosinophilic inclusion bodies in the mucosal epithelia. The remaining dog from
      this area showed vomiting, but not diarrhoea, and also had a number of
      intraepithelial inclusion bodies in the gastric and intestinal mucosa. In
      contrast, the seven dogs from the Tokyo area showed neither gastrointestinal
      symptoms nor intraepithelial inclusions in the stomach or intestine.
      Immunohistochemical examination for CD virus antigen, however, revealed that
      these seven dogs had immunoreactive products in the mucosal epithelia, suggesting
      that the epithelial cells had either a low level of infection with CD virus or
      were infected with a less cytopathogenic virus. These findings suggest that the
      dogs in this study were probably affected by two distinct types of CD, in terms
      of epitheliotropism and cytopathogenic effects on the gastrointestinal tissues.

PMID- 9179754
TI  - Combined hepatocellular carcinoma and cholangiocarcinoma in a mare.
AB  - A hepatic malignant tumour composed of both hepatocellular and cholangiocellular
      elements was studied histologically, immunohistochemically and electron
      microscopically in an 18-year-old Thoroughbred mare. Bile canaliculi and alpha
      fetoprotein were useful in identifying the hepatocellular element, and mucin and
      keratin were good markers of biliary differentiation. The simultaneous presence
      of bile canaliculi and mucin-producing cells in most of the neoplastic lesions
      suggested that this tumour arose from a stem cell with capacity to differentiate
      into hepatocytes and biliary epithelium.

PMID- 9179755
TI  - Pulmonary venous thrombosis in caprine Pasteurella pneumonia.
AB  - A 3-year-old Angora goat that developed acute fibrinous pleuropneumonia
      associated with Pasteurella haemolytica infection had thrombotic occlusion of a
      large pulmonary vein. Thrombosis of pulmonary capillaries occurs in pneumonic
      pasteurellosis, but large vessels are not commonly affected. This unusual lesion
      may reflect the procoagulant effect of pasteurella endotoxin on vascular
      endothelium. An incidental observation was the presence of myocardial-type muscle
      fibres in the tunica media of the pulmonary vein.

PMID- 9179756
TI  - Detection of coxsackie B virus RNA sequences in whole blood samples from adult
      patients at the onset of type I diabetes mellitus.
AB  - Enteroviruses may be linked to insulin-dependent diabetes mellitus (IDDM). The
      prevalence of enteroviral (EV) infection at onset of adult IDDM was investigated
      by detection of specific EV sequences in peripheral blood using a reverse
      transcription and a seminested polymerase chain reaction (seminested RT-PCR).
      EDTA-treated whole blood samples taken from 12 newly diagnosed IDDM patients with
      ketosis or ketoacidosis were examined. The comparison groups were 12 adult
      patients suffering from metabolic decompensation in the course of IDDM, 12 adult
      patients with decompensated non-IDDM, and 15 healthy adults without any presumed
      EV infection or metabolic disease. EV genome was detected in five of 12 (42%)
      newly diagnosed IDDM patients and in one of 12 (8%) patients in the course of
      IDDM. By contrast, none of the 12 non-IDDM patients and none of the 15 healthy
      adults had EV sequences in whole blood. Subsequent sequencing of the EV PCR
      products from the six positive patients showed a significant homology with
      Coxsackie B3 or B4 viruses, and some common patterns were observed among the
      sequences. The present study demonstrates that Coxsackie B virus RNA sequences
      can be detected in peripheral blood from patients at the onset or in the course
      of IDDM and provides evidence for a role for enteroviruses in adult type I
      diabetes.

PMID- 9179757
TI  - Mapping of the cellular immune responses to woodchuck hepatitis core antigen
      epitopes in chronically infected woodchucks.
AB  - T-cell responses to hepatitis B virus nucleocapsid antigens (HBcAg and HBeAg)
      play an important role in disease outcome in those infected with hepatitis B
      virus (HBV). The woodchuck is naturally infected in the wild with woodchuck
      hepatitis virus (WHV), which shows a high degree of genetic homology to HBV and
      produces a similar pattern of infection in its natural host. Twenty-three
      overlapping peptides were constructed to cover the entire WHV core region and
      used to identify immunodominant cellular epitopes in the nucleocapsid antigen
      using peripheral blood lymphocytes from 12 chronic WHV carrier and 4 uninfected
      control animals. A peripheral blood lymphocyte response was seen in all of the
      chronic WHV carrier animals to at least one peptide, and in 8 of the 12 chronic
      carrier animals a response was observed to 5 common peptides: peptide analogues
      of amino acids 16-30, 38-52, 50-69, 76-90 and 91-105. Peptide 91-105 produced
      maximal proliferation in 5 out of 12 infected animals. In addition, a difference
      in response was observed between wild and laboratory infected animals; the latter
      appeared to have a lower response to peptides than animals infected in the wild.
      This study provides evidence that the woodchuck has a population of peripheral
      blood cells which are sensitised to epitopes within the nucleocapsid protein and
      provides a basis on which to develop the use of the woodchuck as an immunological
      model of HBV infection for testing therapeutic means of enhancing this response.

PMID- 9179758
TI  - Distribution of herpes simplex virus types 1 and 2 genomes in human spinal
      ganglia studied by PCR and in situ hybridization.
AB  - Clinical data indicate that the recurring herpes simplex virus (HSV) from oro
      labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV-2.
      This suggests that HSV-1 and HSV-2 reside in latent forms in the trigeminal
      ganglia and sacral ganglia, respectively. However, the distribution of latent HSV
      1 and HSV-2 infections in human spinal ganglia has not been fully examined. This
      report concerns the application of polymerase chain reaction (PCR) and in situ
      hybridization (ISH) to such a study. By using PCR and employing the respective
      primers, HSV-1 and HSV-2 DNAs were detected in 207 of 524 samples from 262 spinal
      ganglia (from the cervical to the sacral ganglia) examined on both sides. The
      percentages of HSV-1 and HSV-2 detected in a given set of ganglia were similar,
      indicating an absence of site preference. By ISH, few but positive hybridization
      signals were detected evenly in sacral ganglia sections. The data suggest that
      regional specificity of recurrent HSV infections is not due to regional
      distribution of latent virus, but that local host factors may be important for
      recurrences.

PMID- 9179759
TI  - Prevalence and molecular epidemiology of GB virus C/hepatitis G virus infection
      in Mongolia.
AB  - We studied the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection
      among 112 patients with liver disease and 121 blood donors in Ulaanbaatar,
      Mongolia. Reverse transcription and polymerase chain reaction were employed to
      detect GBV-C/HGV RNA using the specific primers derived from the 5'-untranslated
      region (5'-UTR) of the GBV-C/HGV genome. Nucleotide sequences of all positive
      samples for GBV-C/HGV RNA were determined. The sequences were analyzed by a
      molecular evolutionary method. Twenty-five (10.7%) of 233 people were positive
      for GBV-C/HGV RNA. Eight (6.6%), 11 (9.1%), and 30 (24.8%) blood donors were
      positive for GBV-C/HGV RNA, HBsAg, and anti-HCV, respectively, although 17
      (15.2%), 65 (58.0%), and 64 (54.5%) patients with liver disease were positive for
      each viral marker. The prevalences of GBV-C/HGV RNA, HBV, and HCV in the patients
      were significantly higher than those in blood donors (P < 0.05). There was no
      significant difference in the prevalence of anti-HCV among people with and
      without GBV-C/HGV RNA, while the prevalence of HBsAg among people with GBV-C/HGV
      RNA was significantly higher than among those without GBV-C/HGV RNA (P < 0.05).
      The molecular evolutionary tree showed that GBV-C/HGV was a heterogeneous virus
      and all strains could be divided into 2 types. One is the same phylogenetic type
      as HGV, and the other is a new type that is different from GBV-C and HGV.

PMID- 9179760
TI  - High prevalence of GB virus C strains genetically related to strains with Asian
      origin in Nicaraguan hemophiliacs.
AB  - The presence of hepatitis GB virus C (GBV-C), also known as hepatitis G virus
      (HGV), and hepatitis C virus (HCV) were investigated in sera from 45 hemophiliacs
      from nine locations in Nicaragua using a nested polymerase chain reaction (PCR).
      Primers used to detect GBV-C and HCV derived from the helicase region and 5'UTR,
      respectively. Seventeen (38%) patients were positive for GBV-C RNA in serum by
      PCR. Twelve (27%) patients were positive for HCV RNA by PCR. Six (13%) of these
      were coinfected with GBV-C. Anti-HCV was detected in all the 12 HCV RNA positive
      hemophiliacs and in another 14 (31%) individuals, in whom GBV-C RNA was found in
      2. Ten patients (22%) lacked markers for both GBV-C and HCV. The mean age of the
      patients positive for GBV-C but negative for HCV by PCR was significantly lower
      than for those negative for GBV-C but positive for HCV by PCR (P < 0.05;
      Student's t-test), indicating that the risk for this group of hemophiliacs to
      acquire GBV-C infection is higher as compared to the risk of acquiring HCV
      infection. Eleven GBV-C strains were sequenced in the 5'UTR. Sequence comparison
      to previously published GBV-C strains revealed that all 11 strains were more
      similar to Asian strains than to strains of European and African origin.
      Sequences in the NS5-B region were available for 8 HCV strains, all of which were
      found to belong to genotype 1a. The similarity of the Nicaraguan GBV-C strains to
      strains from Asia indicates that the GBV-C strains in the region presumably have
      an Amerindian origin. It is also considered that the HTLV II strains in the New
      World aboriginal populations are ancient and brought there by the ancestral
      Amerindian populations from Asia. Further, the genotype F of hepatitis B virus,
      known to represent the strains in populations with Amerindian background,
      predominates in Central American populations with Hispanic background. It remains
      to be clarified why Amerindian strains of GBV-C as well as of HBV predominate
      also in populations with mixed ethnic background in Central America.

PMID- 9179761
TI  - Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients
      with the co-infection.
AB  - Of 74 patients who were infected with hepatitis C virus (HCV) and received
      interferon, 12 (16%) were positive for RNA of GB virus C (GBV-C). RNA of GBV-C
      was determined in sera from the co-infected patients retrospectively, and the
      effect of interferon on GBV-C was compared with that on HCV in them. Titers of
      both GBV-C and HCV RNAs decreased during interferon in all of them. Two patients
      lost both GBV-C and HCV RNAs and remained clear until 6 months after treatment
      with interferon, while 2 lost RNA for GBV-C only and 2 for HCV RNA alone. Low
      pretreatment RNA titers of GBV-C and HCV correlated with the efficacy of
      interferon in clearing. Alanine aminotransferase returned to normal only in the
      patients who lost HCV RNA, regardless of the persistence or loss of GBV-C RNA.
      These results indicate that the response to interferon of GBV-C is comparable to
      but independent of that of HCV and that the persistence of GBV-C would not
      prevent the normalization of aminotransferases in response to interferon in
      patients with chronic hepatitis C.

PMID- 9179762
TI  - Acute hepatitis C viral infection during pregnancy: failure of mother to infant
      transmission.
AB  - A pregnant woman developed an acute hepatitis C virus (HCV) type 3a infection
      during the second trimester of pregnancy. The clinical virological features are
      presented, including HCV RNA quantification of maternal serum samples collected
      during pregnancy. These findings are discussed in light of the child's remaining
      uninfected after 5 years of follow-up.

PMID- 9179763
TI  - Importance of sexual transmission of hepatitis C virus in seropositive pregnant
      women: a case-control study.
AB  - The mode of hepatitis C virus (HCV) transmission in patients who deny parenteral
      exposure is still not understood. Seroprevalence studies of anti-HCV in sexually
      promiscuous populations and in spouses of infected patients have given
      contradictory results. We investigated the role of sexual transmission of HCV in
      a case-control study of risk factors for infection in a series of 43 anti-HCV
      positive pregnant women and 172 matched controls (4 for each case). In the
      univariate analysis, the following factors were associated significantly with
      anti-HCV seropositivity: low social class, unmarried, history of abortion, wounds
      which were sutured, tattooes, sharing toiletries with the partner, sexual contact
      outside the partnership without condom use, blood transfusion, and intravenous
      drug abuse, but only the last 3 factors remained significantly associated with
      HCV infection in multiple logistic regression analysis. The relative risk of HCV
      infection increased according to the increased number of sexual partners. Thus
      sexual transmission must be considered a possible mode of infection in HCV
      infected persons without parenteral exposures.

PMID- 9179764
TI  - Detection of human herpes virus 8 DNA and sequence polymorphism in classical,
      epidemic, and iatrogenic Kaposi's sarcoma in South Africa.
AB  - The aetiology and detection of human herpes virus type 8 (HHV-8) DNA sequences in
      Kaposi's sarcoma (KS) is a matter of intense investigation. We report on the
      detection of HHV-8 DNA and sequence polymorphism in different clinicopathological
      subtypes of cutaneous KS samples from South Africa. The diagnosis was confirmed
      by histological examination in all cases. Six patients had classic KS (CKS), 3
      epidemic KS (EKS), and 3 iatrogenic KS (IKS). A nested polymerase chain reaction
      (PCR) assay was used to detect HHV-8 DNA in cell lysates, prepared from formalin
      fixed, paraffin embedded sections. We investigated polymorphism in the HHV-8 DNA
      using single-stranded conformational polymorphism (SSCP) analysis on the PCR
      products, followed by direct sequencing. HHV-8 DNA was detected in all the
      patients with KS, irrespective of the clinicopathological subtype. Direct
      sequencing was performed on 5 selected cases and showed single base pair
      substitutions in all. The spectrum of mutations was similar to those described
      previously. No correlation was found between the different types of KS and
      sequence variation. The results support the hypothesis that HHV-8 is strongly
      associated with different clinicopathological subtypes of KS and confirm the
      occurrence of HHV-8 in patients with CKS, EKS, and IKS in South Africa.

PMID- 9179765
TI  - Parkville virus: a novel genetic variant of human calicivirus in the Sapporo
      virus clade, associated with an outbreak of gastroenteritis in adults.
AB  - This report describes the characterization of Parkville virus, the etiologic
      agent of an outbreak of foodborne gastroenteritis, that has the morphology of a
      calicivirus and genetic properties that distinguish it from previously identified
      strains in the Sapporo/Manchester virus clade. Sequence analysis of the Parkville
      virus genome showed it contained the RNA-dependent RNA polymerase motifs GLPSG
      and YGDD characteristic of members of the family Caliciviridae with an
      organization identical to that reported for the Manchester virus where the capsid
      region of the polyprotein is fused to the RNA polymerase. Parkville virus
      however, demonstrates considerable sequence divergence from both the Manchester
      and Sapporo caliciviruses, providing the first indications that genetic diversity
      exists within caliciviruses of this previously homogeneous clade. On the basis of
      recent advances in the genetic characterization of members of the family
      Caliciviridae, we propose a new interim phylogenetic classification system in
      which Parkville virus would be included with Manchester and Sapporo virus as a
      separate group distinct from the small round-structured viruses (Norwalk-like
      viruses) that also cause diarrhea in humans.

PMID- 9179766
TI  - Rapid and sensitive detection of cell-associated HIV-1 in latently infected cell
      lines and in patient cells using sodium-n-butyrate induction and RT-PCR.
AB  - To develop a rapid and sensitive means of detecting cell-associated human
      immunodeficiency virus (HIV), donor cells from HIV seropositive patients were
      treated with the potent viral activator sodium-n-butyrate (NaB) and subsequently
      assayed by both in situ RNA hybridization and a reverse transcriptase polymerase
      chain reaction (RT-PCR). The sensitivity of RT-PCR was estimated to be equivalent
      to 1 x 10(-16) grams (0.1 fg) or approximately 64 copies of the input standard
      viral RNA per reaction. The present study takes advantage of the ability of NaB
      to introduce changes in chromatin structure of latently infected cells, leading
      to increased HIV gene expression. Human ACH-2 and U1 cell lines were used as
      representatives of T-lymphocytic and monocytoid cells harboring latent inducible
      proviruses. HIV gene expression was readily detected when these cells were
      treated with NaB. Viral gag RNA was detected by both in situ and RT-PCR assays.
      When peripheral blood mononuclear cells (PBMCs) from acquired immunodeficiency
      syndrome (AIDS) patients, who were all negative for in situ hybridization and
      serum/plasma p24 assays, were used for detection of viral gene expression, four
      categories with distinct patterns of induction were observed. The first set of
      patients showed HIV-positive PBMCs by RT-PCR without any added NaB, and
      suppression by added NaB or PHA. The second set of samples showed induction of
      viral RNA by NaB alone. The third set could be induced with PHA, but not NaB, and
      the fourth set required both NaB and PHA for induction of HIV gene expression.
      Our results suggest that direct treatment of the cells with HIV activators may be
      useful in increasing sensitivity of the RT-PCR intended to be used for detection
      of cell-associated viral RNAs. This approach may be used to confirm true status
      of the HIV infection when p24 results are negative or HIV RNAs in serum/plasma
      are below the threshold of detection. Moreover, this method may identify the
      presence of latent proviral genomes possibly reflecting the true rate of cell
      associated viral load in vivo and without possible mutations brought about by
      long-term co-cultivation assays with cells from seronegative donors.

PMID- 9179767
TI  - Differential flotation centrifugation study of hepatitis C virus and response to
      interferon therapy.
AB  - Hepatitis C virus (HCV) appears to circulate in various forms such as native
      virion, immune complexes, and nucleocapsids during chronic infections. To
      determine the association of the physicochemical properties of HCV and its
      response to interferon therapy in patients with chronic hepatitis C, we examined
      pretreatment serum samples from 43 patients with HCV RNA who had received
      interferon therapy, using differential flotation centrifugation in a NaCl
      solution with a density of 1.063 g/ml. After centrifugation, the ratio of HCV RNA
      in the top and bottom fractions was determined by the polymerase chain reaction
      and expressed as T/B. Patients with a sustained response to IFN therapy were
      found to have higher T/B ratios than transient responders who relapsed after
      treatment (P < 0.01) and nonresponders (P < 0.01). With regards to HCV genotypes,
      patients with genotype 1b had higher T/B ratios in the sustained response group
      than in the nonsustained response groups (P = 0.001), but patients with genotype
      2 had a similar distribution of T/B among the 3 response groups (not
      significant). These findings indicate that the physicochemical properties of HCV
      affect the effectiveness of interferon therapy, particularly in patients with
      genotype 1b.

PMID- 9179769
TI  - Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus
      disease after renal transplantation.
AB  - Studies have shown that risk factors for human cytomegalovirus (HCMV) disease
      after renal transplant include primary infection (virus of donor origin infecting
      a non-immune individual), re-infection (virus of donor origin infecting a immune
      individual), and the detection of viraemia (as a marker of virus dissemination).
      We now report that viral load in the urine is also a significant factor in HCMV
      disease and is one of the main mechanisms underlying the risk associated with
      viraemia and donor serostatus. Longitudinal analysis of a group of 196 renal
      recipient identified 35 recipients who were PCR positive for HCMV in urine.
      Elevated viral loads were present in symptomatic patients, viraemic patients, and
      patients experiencing primary HCMV infection. Disease was associated with the
      peak quantity of virus present in the urine during the post-transplant period (P
      = 0.0001), with viraemia (P = 0.0003), and with transplantation of a seropositive
      donor (P = 0.03). Univariate logistic regression analysis showed that increases
      of 0.25 log10 in viral load were associated with a 179% increased risk of disease
      (odds ratio = 2.79; 95% C.I. 1.22-6.39; P = 0.02). This effect persisted in a
      multivariate logistic analysis when viraemia was incorporated (odds ratio = 2.77;
      95% C.I. 1.07-7.18; P = 0.04). In contrast, the significant association between
      viraemia and disease observed in univariate analysis (odds ratio = 23.75; 95%
      C.I. 3.69-152.90; P = 0.0009) became marginally non-significant in multivariate
      analysis once viral load had been controlled for (odds ratio = 34.54; 95% C.I.
      0.75-1599.00; P = 0.07). The computed probability of disease showed that a rapid
      transition occurred at viral loads between 10(5.7) and 10(6.5) genomes/ml urine
      in non-viraemic patients compared to viral loads between 10(5.0) and 10(5.7)
      genomes/ml urine in patients with concurrent viraemia. The implications of these
      findings for understanding HCMV pathogenesis, improving patient management, and
      optimising trials of antiviral treatment are discussed.

PMID- 9179768
TI  - Detection of mumps virus genome directly from clinical samples and a simple
      method for genetic differentiation of the Hoshino vaccine strain from wild
      strains of mumps virus.
AB  - A simple and sensitive method was developed for the differentiation of the
      Hoshino vaccine strain from wild strains with a restriction fragment length
      polymorphism (RFLP) analysis in the part of hemagglutinin-neuraminidase (HN)
      gene. The virus genome was amplified by using a reverse transcriptase-polymerase
      chain reaction (RT-PCR) directly from clinical samples. The PCR product of the
      Hoshino vaccine strain was cleaved into 2 fragments after digestion with Sca I
      and Afl II. All wild strains showed 2 RFLP profiles, A and B, different from that
      of vaccine strain. Wild A strains were cut into 2 fragments after digestion with
      Sca I only, while wild B strains were cleaved neither with Sca I nor Afl II. This
      molecular approach provides an effective method for differentiation of the
      Hoshino vaccine strain from wild strains of mumps virus in patients after
      vaccination.

PMID- 9179770
TI  - Experimental CVB3-induced chronic myocarditis in two murine strains: evidence of
      interrelationships between virus replication and myocardial damage in persistent
      cardiac infection.
AB  - In order to analyse the relationships between enteroviral replication and the
      myocardial damage at the onset of chronic cardiac infection, 2 mouse strains with
      different degrees of immunological competence (NMRI nu/nu, DBA/2) were infected
      by a myocarditic Coxsackie virus B3 (CVB3-M1) variant. At 31 days post
      inoculation, plaque-forming assay, polymerase chain reaction (RT-PCR), and
      immunohistochemistry were carried out for detecting viruses and viral components
      in the myocardium. The virological findings were related to histopathological
      changes in the myocardium as well to the dilatation of both cardiac ventricles.
      Chronic myocardial lesions characterized by large fibrosis areas and interstitial
      inflammatory infiltrates were detected together with cardiomegalia in 52.6%
      (10/19) of athymic mice and in 9% (2/22) of euthymic mice. Viral replication foci
      were located and were found only in myocarditic cells adjacent to myocardial
      inflammatory lesions by immunostaining myocardial tissue sections with anti-serum
      to VP1 virus capsid protein. Using PCR followed by microwell capture
      hybridization assay, a large excess of viral positive strand RNA over negative
      strand was semiquantified in heart tissue from mice with chronic myocarditis,
      whereas approximately equal amounts of plus and minus strand RNA were detected in
      cases of persistent cardiac infection without chronic myocardial injuries. These
      findings provide evidence of the major role of viral replication in the
      pathogenesis of chronic murine CVB3-induced cardiomyopathy. The results indicate
      that the cardiac persistence of enteroviral RNAs can be observed without chronic
      cardiomyopathy, which could be explained by a defective viral positive RNA
      replication.

PMID- 9179771
TI  - Safety and immunogenicity of inactivated hepatitis A vaccine in patients with
      chronic liver disease.
AB  - The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in
      patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV)
      seronegative patients with chronic liver disease (56 chronic hepatitis B and four
      chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA
      units of the inactivated hepatitis A vaccine at month 0, and a booster at month
      6. Anti-HAV seroconversion (> or = 33 mIU/mL) was 57.6% (34/59) on day 15, and
      reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the
      seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All
      vaccinees had measurable titers of anti-HAV 1 month after booster vaccination,
      and were still seropositive at month 12. After initial vaccination, the geometric
      mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409
      mIU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the
      vaccine doses administered were followed by mostly minor reactions. The majority
      of symptoms reported were local, all of which resolved within 3 days after
      vaccination. No significant changes in serum liver enzyme levels were detected
      after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients
      with chronic liver disease while the immune response was inferior to that
      observed in healthy subjects reported in a previous study.

PMID- 9179772
TI  - Hepatitis C (HCV) genotype and viral titer distribution among Argentinean
      hemophilic patients in the presence or absence of human immunodeficiency virus
      (HIV) co-infection.
AB  - Hepatitis C (HCV) infection is frequent among hemophilic patients treated with
      non-inactivated factor-concentrates. Both HCV genotype and viral load have been
      suggested to be important prognostic markers of disease progression and treatment
      outcome. In addition, co-infection with the human immunodeficiency virus (HIV)
      has been associated with increased level of HCV replication and higher risk of
      developing liver failure. Thus, HCV genotype, viral load, and HIV co-infection
      are important factors in HCV infection. Using restriction fragment length
      polymorphism analysis (RFLP) and the branched-DNA (bDNA) assay, we
      retrospectively investigated the HCV genotypes and viral loads present in 59
      Argentinean hemophiliacs, in the presence or absence of HIV infection. HCV
      genotype 1 was the predominant viral variant detected among HIV-negative (HIV-)
      (76%) and HIV-positive (HIV+) (82.5%) patients, followed by genotypes 3 (10.4%),
      2 (2%) and a small proportion of multiply co-infected patients including
      genotypes 4 and 5 (6.25%). HIV+ patients had higher plasma HCV RNA levels than
      HIV- patients (88.4 +/- 16.5 x 10(5) Eq/ml vs. 24.7 +/- 10(5) Eq/ml) (P < 0.001);
      however, no correlation between HCV replication and level of immune suppression,
      evaluated by CD4+ T-cell measurement, was observed among HIV+ patients (r =
      0.017). Abnormal and higher ALT levels were more frequently detected among HIV+
      (93%; 123.6 +/- 15.7 U/liter) than HIV- (41%; 70.2 +/- 24.2 U/liter) patients (P
      < 0.001; P < 0.05). Although we were able to confirm previous reports suggesting
      the existence of increased HCV replication in HIV/HCV co-infected hemophiliacs,
      our data did not support the conclusion that HIV-induced immune suppression is
      directly responsible for this phenomena. It is possible that other factors
      induced by HIV are responsible for the increased levels in HCV replication
      observed.

PMID- 9179773
TI  - In vitro neutralization of hepatitis B virus by monoclonal antibodies against the
      viral surface antigen.
AB  - In vitro HBV infection and neutralization were assayed using an anti-preS1 murine
      monoclonal antibody (1B3) and anti-preS2 (H69K) and anti-S (CS131A) murine-human
      chimeric antibodies. The 1B3 (IgG1) and H69K (IgG1) was constructed previously
      and the CS131A was constructed for this study by expressing stably the chimeric
      heavy and light chains in Chinese hamster ovary cells and purifying from the
      culture supernatant. Previous study showed that the H69K and CS131A recognize
      known virus-neutralizing epitopes, while the 1B3 does not. For the assays, adult
      human hepatocyte primary culture was infected with the adr or ayw subtype of HBV,
      and the infectivity and subsequent replication was confirmed both by measuring
      the kinetics of HB-sAg secretion by the infected cells and detecting the
      intermediate replicative form of HBV DNA in the cells. Next, the hepatocytes were
      infected with the adr or ayw subtype of the virus that had been preincubated with
      various concentrations of each of the antibodies and the neutralization of HBV
      was analyzed. The results showed that the anti-preS2 and anti-S chimeric
      antibodies exhibited neutralizing activity against both the adr and ayw subtypes
      of the virus, with approximately 1,000 and 2,000 times higher specific activity
      than polyclonal hepatitis B immune globulin, respectively, but the anti-preS1
      antibody scarcely neutralized the infection. The neutralizing activities of the
      antibodies were consistent with their epitope specificity and antigenbinding
      affinity, suggesting that this neutralization assay is specific. The in vitro
      neutralization assay will be useful for evaluating the neutralizing activity of
      anti-HBV antibodies before in vivo testing in chimpanzees.

PMID- 9179774
TI  - Structural studies of spider silk proteins in the fiber.
AB  - Although spider silk has been studied for a number of years the structures of the
      proteins involved have yet to be definitely determined. X-ray diffraction and
      solid-state nuclear magnetic resonance (NMR) were used to study major ampullate
      (dragline) silk from Nephila clavipes. The silk was studied in its natural state,
      in the supercontracted state and in the restretched state following
      supercontraction. The natural silk structure is dominated by beta-sheets aligned
      parallel to the fiber axis. Supercontraction is characterized by randomizing of
      the orientation of the beta-sheet. When the fiber is restretched alignment is
      regained. However, the same reorientation was observed for wetting of minor
      ampullate silk which does not supercontract. Thus, the reorientation of beta
      sheets alone cannot explain the supercontraction in dragline silk. Cocoon silk
      showed very little beta-sheet orientation in the natural state and there were no
      changes upon wetting. NMR and X-ray diffraction data are consistent with the beta
      sheets arising from the poly-alanine sequences known to be present in the
      proteins of major ampullate silk as has been proposed previously.

PMID- 9179775
TI  - Detection of mutations in PCR products from clinical samples by surface plasmon
      resonance.
AB  - Two different strategies for scanning and screening of mutations in polymerase
      chain reaction (PCR) products by hybridization analysis are described, employing
      real-time biospecific interaction analysis (BIA) for detection. Real-time BIA was
      used to detect differences in hybridization responses between PCR products and
      different 17-mer oligonucleotide probes. For the analysis using a biosensor
      instrument, two different experimental formats were investigated based on
      immobilization of either biotinylated PCR products or oligonucleotide probes onto
      a sensor chip. Applied on the human tumour suppressor p53 gene, differences in
      hybridization levels for full-match and mismatch situations employing both
      formats allowed the detection of point mutations in exon 6 PCR products, derived
      from a breast tumour biopsy sample. In addition, a mutant sample sequence could
      be detected in a 50/50 background of wild type exon 6 sequence. The suitability
      of the different formats for obtaining a regenerable system and a high throughput
      of samples is discussed.

PMID- 9179776
TI  - Peptide-derived self-assembled monolayers: adsorption of N-stearoyl L-cysteine
      methyl ester on gold.
AB  - The work reported herein concerns the assembly of N-stearoyl L-cysteine methyl
      ester [CH3(CH2)16COCysOMe, 1] on the surface of gold. This compound serves as a
      simple model of a related polypeptide, which has been designed to adopt a beta
      sheet architecture on metallic and oxide surfaces. We describe the preparation of
      monolayers of 1, and characterization of these layers via ellipsometry,
      vibrational spectroscopy and X-ray photoelectron spectroscopy. The results are
      most consistent with a disordered array of the alkyl chains, in which close
      packing is frustrated by a mismatch in the cross-sectional areas of the cysteinyl
      ester head group and the stearoyl chains of the thiol. Despite the disorder, the
      alkyl chains form a hydrophobic surface layer, with an advancing contact angle
      for water comparable to that observed for octadecanethiol on gold.

PMID- 9179777
TI  - Crystal structure of the bovine alpha-chymotrypsin:Kunitz inhibitor complex. An
      example of multiple protein:protein recognition sites.
AB  - The crystal structure of bovine alpha-chymotrypsin (alpha-CHT) in complex with
      the bovine basic pancreatic trypsin inhibitor (BPTI) has been solved and refined
      at 2.8 A resolution (R-factor = 0.18). The proteinase:inhibitor complex forms a
      compact dimer (two alpha-CHT and two BPTI molecules), which may be stabilized by
      surface-bound sulphate ions, in the crystalline state. Each BPTI molecule, at
      opposite ends, is contacting both proteinase molecules in the dimer, through the
      reactive site loop and through residues next to the inhibitor's C-terminal
      region. Specific recognition between alpha-CHT and BPTI occurs at the (re)active
      site interface according to structural rules inferred from the analysis of
      homologous serine proteinase:inhibitor complexes. Lys15, the P1 residue of BPTI,
      however, does not occupy the alpha-CHT S1 specificity pocket, being hydrogen
      bonded to backbone atoms of the enzyme surface residues Gly216 and Ser217.

PMID- 9179778
TI  - Comparative studies on the interaction of proteins with a polydimethylsiloxane
      elastomer. I. Monolayer protein capture capacity (PCC) as a function of protein
      pl, buffer pH and buffer ionic strength.
AB  - Polydimethylsiloxane (PEP) is widely used in medical prostheses and therefore is
      in contact with plasma and secretory proteins. Two pair of globular proteins,
      lactoferrin (Lf) and transferrin (Trf), and bovine IgG1 and IgG2a, which differ
      substantially between pair members in their pl, were used to study the
      interaction of a PEP widely used in breast implants and soluble protein. Studies
      were done using iodinated proteins over a concentration range that resulted in an
      apparent protein monolayer. Secondary incubations with dilute protein solutions
      were needed to form the monolayer on PEP, possibly as a consequence of micro air
      bubbles trapped on its highly textured surface as shown by atomic force
      microscopy. Immunoassay quality polystyrene microtiter wells were used as
      controls. Adsorption studies were routinely performed at pH 4, 7 and 10 and at
      ionic strengths corresponding to 0.95, 9.5 and 90.0 mS. The protein capture
      capacity (PCC) of PEP for Lf and Trf was optimal at physiological pH and ionic
      strength and comparable under these conditions to that of Immulon 2 (Imm 2)
      microtiter wells. While increasing the ionic strength and pH further increases
      the PCC of Imm 2 for Lf and Trf, this markedly lowered the PCC of PEP for these
      proteins suggesting that initial polar interactions may precede subsequent
      hydrophobic bonding to PEP. This was tested using a hydrophilic variant of PEP,
      which when tested in a 90.0 mS buffer, showed a > five-fold lower PCC at neutral
      and alkaline pH. The greatly reduced PCC of the hydrophilic variant might also
      suggest that hydrophilic variants of silicone would be more biocompatible than
      those currently used. The PCC of PEP for the IgGs was less than that of Imm 2 but
      still optimal at physiological conditions. Consistent with the data on Lf/Trf,
      PCC progressively decreased with increasing ionic strength at alkaline pH.
      Differences in pl between the protein pairs had only a marginal effect on the PCC
      of PEP. Monolayer adsorption on both PEP and Imm 2 was slowly reversible and
      greater in the presence of free ligand (< 2% in 16 h) suggesting that the process
      follows Mass Law principles. However, even in the presence of non-ionic detergent
      and free ligand, 85-90% remained bound on either surface. Thus, desorption of
      proteins in the monolayer should not complicate subsequent immunochemical studies
      conducted on adsorbed monolayers.

PMID- 9179779
TI  - Comparative studies on the interaction of proteins with a polydimethylsiloxane
      elastomer. II. The comparative antigenicity of primary and secondarily adsorbed
      IgG1 and IgG2a and their non-adsorbed counterparts.
AB  - The antigenicity of bovine IgG1 and IgG2a adsorbed on a polydimethysiloxane (PEP)
      elastomer, on a widely used polystyrene (Imm 2, Dynatech) or immobilized as
      biotinylated proteins to streptavidin covalently bound to polystyrene (SA-PS) was
      compared using various monoclonal (mAbs) and polyclonal antibodies (pAb) to
      bovine IgG. The IgGs were either adsorbed as native proteins or pre-denatured
      with 6M Guanidine-HCl (Gu-HCl) or 6 M Gu-HCl/0.1% 2-mercaptoethanol. In special
      situations, bovine and human IgG was immobilized by secondary adsorption to an
      albumin monolayer adsorbed on either PEP or Imm 2. Results indicate that pre
      denaturation of IgGs with 6 M Gu-HCl/2-mercaptoethanol destroys all antigenicity
      whereas those IgGs pretreated with 6 M-GuHCl are indistinguishable in their
      antigenicity from the IgGs adsorbed to either PEP or Imm 2 without such
      treatment. When immobilized on SA-PS, Gu-HCl-treated IgGs were significantly less
      detectable, especially when tested using mAbs. In general, IgGs adsorbed on PEP
      or Imm 2 were less antigenic than when immobilized on SA-PS. However, two
      monoclonals specific for the IgG2a(A2) allotypic variant, favored the adsorbed
      protein and one polyclonal best recognized the IgG2a(A1) variant adsorbed on Imm
      2 rather than when adsorbed on PEP or immobilized on SA-PS. Both IgG1 and IgG2a,
      bound by apparent protein-protein interactions to an albumin monolayer, were
      significantly more detectable than when directly adsorbed on either Imm 2 or PEP.
      Using 125I-antibody or its Fab fragment to reduce steric hindrance in detection,
      we observed the same differences in detectability as when measured by enzyme
      linked immunosorbent assay. Failure to identify a steric hindrance effect and the
      preference of some antibodies for adsorbed allotypic variants, support the
      concept of adsorption-induced conformational change (AICC). We conclude that
      proteins adsorbed as a monolayer on the PEP elastomer used to form the envelope
      of silicone breast implants are conformationally altered, but not necessarily to
      the same extent or the same manner as when adsorbed on polystyrene. The
      significantly great antigenicity of secondarily adsorbed IgG suggests that it may
      be present in near native conformation.

PMID- 9179780
TI  - Herpes simplex virus virulence: the functions of the gamma (1)34.5 gene.

PMID- 9179782
TI  - Use of primary CNS cultures to investigate HIV neurotropism.

PMID- 9179781
TI  - Molecular and cellular aspects of measles virus persistence in the CNS.

PMID- 9179783
TI  - HIV neuropathogenesis.

PMID- 9179784
TI  - Neurobiology of Borna disease virus.

PMID- 9179785
TI  - Neurotoxicity and neuroinvasiveness of prions.

PMID- 9179786
TI  - The regulation of gene expression in neurotrophic viruses.

PMID- 9179787
TI  - Neuroglial ATF/CREB factors interact with the human immunodeficiency virus type 1
      long terminal repeat.

PMID- 9179788
TI  - Modulation of mouse hepatitis virus infection by defective-interfering RNA
      mediated expression of viral proteins and cytokines.

PMID- 9179789
TI  - Determinants of poliovirus neurovirulence.

PMID- 9179790
TI  - Alzheimer's disease: a dissection of its etiology.

PMID- 9179791
TI  - The role of CD4+ and CD8+ T cells in demyelinating disease following Theiler's
      virus infection: a model for multiple sclerosis.

PMID- 9179792
TI  - Molecular epidemiology and emerging infectious diseases of the nervous system.

PMID- 9179793
TI  - Recent studies on the epidemiology, clinical features and pathogenic mechanisms
      of HTLV-I associated myelopathy (HAM/TSP) and other diseases associated to HTLV.

PMID- 9179794
TI  - Molecular epidemiology of rabies in the United States: reemergence of a classical
      neurotropic agent.

PMID- 9179795
TI  - A genetic approach to study the pathogenesis of Theiler's virus persistent
      infection.

PMID- 9179796
TI  - Immune regulation of coronavirus-induced demyelinating encephalomyelitis.

PMID- 9179797
TI  - Signaling pathways in virus-induced CNS inflammation.

PMID- 9179798
TI  - Epitope spreading leads to myelin-specific autoimmune responses in SJL mice
      chronically infected with Theiler's virus.

PMID- 9179799
TI  - Lack of correlation of Theiler's virus binding to cells with infection.
AB  - The DA strain of Theiler's murine encephalomyelitis virus (TMEV) is a
      picornavirus which infects the murine central nervous system (CNS). During the
      acute stage versus the chronic stage, different cell-types are infected. To
      clarify the shift seen during persistent infection, we have screened various cell
      lines for their ability to support TMEV infection and used virus binding assays
      to determine if there was a correlation between permissiveness and virus binding.
      Cell lines of different origins were able to support virus infection to varying
      degrees. Infectious center assays and viral binding assay demonstrated that
      permissiveness to virus infection and the ability of virus to attach to the cell
      surface did not always correlate.

PMID- 9179800
TI  - Alternative delivery systems for antiviral nucleosides and antisense
      oligonucleotides to the brain.

PMID- 9179801
TI  - Viruses and oncogenes in brain tumors.

PMID- 9179802
TI  - SV40 and human brain tumors.

PMID- 9179803
TI  - Herpes simplex virus vectors for gene transfer to the nervous system.
AB  - Herpes simplex virus (HSV) represents a candidate gene transfer vector for the
      treatment of nervous system disease. It has many natural biological features
      which make it attractive for gene delivery to a variety of tissues. The virus
      naturally establishes a latency in sensory neurons of the peripheral nervous
      system, wherein the virus in maintained as an extrachromosomal DNA element in the
      absence of viral lytic gene expression without altering the metabolism of the
      host neuron. The virus possesses a neuronal latency-specific promoter system
      which remains active long-term, while other viral and cellular promoters are
      repressed. Replication defective virus recombinants have been engineered to
      delete multiple essential immediate early gene functions rendering these new
      mutants significantly less cytotoxic to neurons and other cells in culture.
      Further developments in regulating transgene expression and reducing virus
      toxicity will continue to aid the design and use of these vectors for therapeutic
      applications for the nervous system.

PMID- 9179804
TI  - Chlamydia trachomatis in adolescents: a review.
AB  - Genital infections caused by Chlamydia trachomatis represent the most prevalent
      bacterial sexually transmitted disease in the United States. An estimated 3-4
      million cases annually necessitate the expenditure of more than $2 billion in
      health care costs per year. The ramifications of infection with this organism
      have significant reproductive complications. The objective of this paper is to
      provide the reader with a review of Chlamydia trachomatis in general with
      particular focus on those areas that are pertinent to the adolescent population.
      The authors hereby provide an overview of the clinically pertinent microbiology,
      epidemiology, risk factors, selective screening protocols, diagnostic methods,
      clinical manifestations, and sequelae of C. trachomatis.

PMID- 9179805
TI  - Tuboovarian abscess in the adolescent.
AB  - Tuboovarian abscess is a serious consequence of pelvic inflammatory disease,
      especially in the adolescent population. Early diagnosis and treatment are
      essential to prevent further sequelae including infertility, ectopic pregnancy,
      and chronic pelvic pain. Not all patients, however, present with pelvic pain,
      pelvic mass, fever, and leukocytosis. We present the case of a sexually active 15
      year-old black girl who presented with mild abdominal pain and excessive vaginal
      bleeding without pelvic mass, fever, or leukocytosis. Erythrocyte sedimentation
      rate was 66 mm/h. Pelvic ultrasound revealed bilateral complex ovarian masses. At
      laparoscopy, the patient had bilateral tuboovarian abscesses with extensive
      adhesions to the pelvic side walls. This case illustrates the need for a high
      index of suspicion of tuboovarian abscess in sexually active adolescents.

PMID- 9179806
TI  - Molecular and cytogenetic studies of X inactivation in a patient with
      46,X,del(X)(q22).
AB  - We report on a phenotypically normal girl with a deletion of the distal long arm
      of one X chromosome at Xq22, and spontaneous pubertal development including
      menarche. This suggests that the distal long arm of the X chromosome is not
      crucial for ovarian development. Cytogenetic and polymerase chain reaction (PCR)
      amplification methods both showed preferential inactivation of the deleted X
      chromosome. The PCR-based assay has the additional advantage of identifying the
      paternal origin of the deleted X chromosome.

PMID- 9179807
TI  - Use of Foley catheter to examine estrogenized hymens for evidence of sexual
      abuse.
AB  - An examination technique for the collection of evidence to document physical
      findings of sexual abuse of children uses a Foley catheter in older girls with
      estrogenized hymens. The inflated balloon in the distal vaginal vault puts
      pressure on the hymen, effectively stretching it out and allowing for a more
      accurate view of the hymen edges. This report demonstrates the results in 2 of 17
      adolescent girls who underwent the Foley catheter stretch technique. Patient 1
      was a 13-year-old girl who gave a statement of repeated sexual abuse, including
      penile penetration by an adult male. Patient 2 was a 12-year-old girl who
      disclosed a single episode of sexual assault 1 year previously. After careful
      examination, a Foley catheter (14 Fr) was inserted through the hymen orifice and
      inflated using 40 ml of air. Gentle pulling toward the orifice resulted in
      stretching of the hymenal tissues over the balloon surface of the catheter. After
      photodocumentation of the anatomy of the hymen edges, the balloon was deflated
      and removed.

PMID- 9179808
TI  - Results of cytogenetic investigation in adolescent patients with primary or
      secondary amenorrhea.
AB  - A cytogenetic study of 77 adolescent girls with primary or secondary amenorrhea
      was performed. A pathologic or male karyotype was found in 18 (26.4%) of 68
      patients with primary amenorrhea. In 1 (11.1%) of 9 patients with secondary
      amenorrhea, 46,XX/47,XXX mosaicism was recovered. The importance of the
      cytogenetic investigations in patients with primary or secondary amenorrhea was
      discussed.

PMID- 9179809
TI  - Mayer-Rokitansky-Kuster-Hauser syndrome diagnosed by magnetic resonance imaging
      in a 15-year-old girl.
AB  - STUDY OBJECTIVE: Mayer-Rokitansky-Kuster-Hauser syndrome diagnosed by magnetic
      resonance imaging (MRI) in a 15-year-old girl with primary amenorrhea is
      reported. DESIGN: The presentation, MRI, and the subsequent evaluation and
      treatment of an adolescent female patient with Rokitansky syndrome are described.
      Correlation is made with previous clinical, pathologic, and imaging reports in
      the literature. SETTING: An adolescent girl with primary amenorrhea was referred
      to our institution for completion of her diagnostic work-up. Previous limited
      evaluations suggested the presence of anomalies of the genitourinary tract.
      Further delineation of the suspected congenital defects was necessary.
      PARTICIPANT: The 15-year-old female patient was evaluated by the gynecology
      service. Diagnostic radiology and pediatric urology were consulted.
      INTERVENTIONS: MRI, physical examination under anesthesia, and cystoscopy were
      performed. After initial nonoperative treatment, the patient underwent
      hysterectomy and sigmoid vaginoplasty. MAIN OUTCOME MEASURES: The patient's
      primary amenorrhea was explained. Mayer-Rokitansky-Kuster-Hauser syndrome was
      diagnosed. Vaginal agenesis and widely separated rudimentary uterine horns were
      well shown by the MRI. Associated skeletal anomalies were noted. A treatment plan
      was initiated based on a good understanding of the anatomic defects. RESULTS: The
      MRI and physical examination firmly established the diagnosis. The patient was
      counseled and managed conservatively at first. Hysterectomy and vaginoplasty were
      subsequently performed. CONCLUSIONS: Mayer-Rokitansky-Kuster-Hauser syndrome is
      an unusual mullerian-duct anomaly that is a cause of primary amenorrhea. It can
      be confidently and noninvasively diagnosed with MRI. The MRI demonstration of
      vaginal, cervical, and uterine morphology contributes significantly to treatment
      planning and patient management.

PMID- 9179810
TI  - Gonococcal infection in cerebrospinal fluid and the presence of a
      ventriculoperitoneal shunt.
AB  - BACKGROUND: Neisseria gonorrhoeae is one of the most common organisms associated
      with pelvic disease in a woman of reproductive age. CASE: We present an unusual
      case of cerebrospinal fluid infection with N. gonorrhoeae in a woman with a
      ventriculoperitoneal shunt who complained of abdominal pain. Her shunt was
      removed and after adequate antibiotic therapy, it was re-inserted. CONCLUSION:
      Sexually active women, especially those with ventriculoperitoneal shunts, should
      be encouraged to use a barrier method of contraception, and should have a pelvic
      examination as part of their evaluation when they present with complaints of
      abdominal pain.

PMID- 9179811
TI  - Genital Chlamydia trachomatis infection in pregnant adolescents in east
      Tennessee: a 7-year case-control study.
AB  - STUDY OBJECTIVE: To examine the prevalence, symptomatology, risk factors, and
      other infections associated with urogenital chlamydial infection in pregnant
      teenagers. DESIGN: Retrospective case-control study by medical record review.
      SETTING: Prenatal care clinic for adolescents at University of Tennessee Medical
      Center, Knoxville, Tennessee. PARTICIPANTS: Pregnant adolescents younger than 19
      years of age who were diagnosed with chlamydial infection on the first prenatal
      visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and
      socioeconomic background who came in the same day for the first prenatal visit,
      but were not infected, made up the control group. INTERVENTION: Routine prenatal
      questionnaires regarding personal and medical histories, and routine prenatal
      screening, including pelvic examination with Papanicolaou (PAP) smear and
      laboratory investigations for common genital infections and sexual transmitted
      disease (STDs), were obtained. MAIN OUTCOME MEASURES: Analyzed the prevalence of
      chlamydial infection and compared the infected group to the control group with
      regard to race, behavioral factors, symptoms, prenatal screening results, other
      concurrent genital infections, and histories of STDs. RESULTS: Of a total
      population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia
      trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95%
      confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at
      first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were
      independently associated with chlamydial infection. Age, marital status, number
      of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and
      multiple sex partners were not associated with the infection. Likewise, the
      symptom of vaginal discharge (a complaint of > 70% in each group), other genital
      co-infections (found > 50% in each group, mainly candidiasis and bacterial
      vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs
      or previous chlamydial infection were not significantly different between case
      and control groups. Human papillomavirus infection, trichomonal infection, and
      dysplasia or atypia were found more often in patients infected with chlamydia,
      but were not statistically significant. CONCLUSION: Pregnant adolescents in east
      Tennessee were at risk for chlamydial infection as well as for other genital
      infections and abnormal PAP smears. Routine prenatal chlamydial screening is
      warranted because of a lack of specific symptoms.

PMID- 9179812
TI  - Management quandary. Congenital absence of uterus.

PMID- 9179813
TI  - Cycle of change and improvement.

PMID- 9179814
TI  - What is your diagnosis? Alopecia.

PMID- 9179815
TI  - Feline leukaemia virus: a review of immunity and vaccination.
AB  - The availability feline leukaemia virus (FeLV) vaccines has added a new and
      important dimension to the control of this infectious agent. FeLV vaccination is
      a controversial issue, however, partly because of differences in the formulation
      between the current products, partly because of conflicting claims by vaccine
      manufactures and partly because experimental trials have shown that none of the
      vaccines provides 100 per cent protection against infection. This paper reviews
      the role of the immune response in determining the outcome following exposure to
      FeLV and describes the importance of FeLV subgroups. The five commercial FeLV
      vaccines currently available in the USA and Europe are described and the
      published literature on efficacy studies is summarised. However, these efficacy
      studies are often difficult to interpret for various reasons, including the small
      numbers of animals used; differences in challenge methods, vaccine strains and
      vaccine dose employed; and differences in postchallenge monitoring protocols.

PMID- 9179816
TI  - Repair of femoral trochanteric osteotomy in the dog.
AB  - The records and radiographs of 24 dogs that underwent femoral trochanteric
      osteotomy repair were reviewed. Osteotomy repair was performed with either a pin
      and tension band wire or a lag screw technique. Significant clinical
      complications associated with the osteotomy were identified in one dog (4 per
      cent) six weeks after surgery, although abnormal radiographic changes were
      evident in 15 dogs (62 per cent). The method of repair did not influence healing
      and there were comparable radiographic complication rates. It is concluded that
      femoral trochanteric osteotomy is not associated with significant clinical
      problems, despite a high incidence of abnormal radiographic findings.

PMID- 9179817
TI  - Effect of circumcostal gastropexy on gastric myoelectric and motor activity in
      dogs.
AB  - Gastric electrical and contractile activities were assessed in healthy adult dogs
      on the eighth day after circumcostal gastropexy surgery, using serosal electrodes
      and strain gauge force transducers. Recordings were analysed to determine gastric
      slow wave frequency, presence of gastric slow wave dysrhythmias, gastric slow
      wave propagation velocity, coupling of gastric contractions to slow waves, a
      gastric motility index based on relative contractile amplitudes, and onset of
      gastric contractions after a standardised meal. Overall, gastric electrical and
      contractile activities were relatively unaffected by circumcostal gastropexy.

PMID- 9179818
TI  - Suspected primary immunodeficiency syndrome in three related Irish wolfhounds.
AB  - Three related Irish wolfhound dogs less than one year old presented with a
      history of chronic nasal discharge and signs of lower respiratory tract disease.
      These responded well to treatment initially but were chronically recurring.
      Cursory evaluation of the immune system (full blood counts, globulin
      determination and fractionation, electrophoresis and lymphocyte blastogenesis)
      seemed to indicate a cell-mediated immunodeficiency which, because of the age of
      the patients, is strongly suspected to be primary.

PMID- 9179819
TI  - Suspected mitochondrial myopathy in a Jack Russell terrier.
AB  - A Jack Russell terrier with a history of progressive exercise intolerance was
      examined at the age of four months and again 10 months later. Clinical
      examination revealed a stunted, thin dog with a stilted gait. The dog had raised
      lactate levels before and after feeding and a raised lactate/pyruvate ratio after
      feeding, indicating a metabolic abnormality. Histochemical evaluation of muscle
      biopsies revealed subsarcolemmal accumulation of oxidative activity when stained
      with nicotinamide adenine dinucleotide tetrazollum reductase and ragged red
      fibres when stained with modified Gomori trichrome; all fibre types were
      involved. Ultrastructural examination of the muscle confirmed the presence of
      subsarcolemmal accumulations of mitochondria. Histochemical staining for the
      activity of enzymes of the Krebs cycle, oxidative phosphorylation and other
      metabolic cytosolic enzymes failed to demonstrate an abnormality. In view of the
      clinical picture and the biochemical and histological findings, a tentative
      diagnosis of mitochondrial myopathy was made. The difficulties associated with
      diagnosing mitochondrial disorders are discussed.

PMID- 9179820
TI  - Filaroides hirthi verminous pneumonia in a West Highland white terrier bred in
      Ireland.
AB  - A two-year-old West Highland white terrier, which had failed to thrive from six
      months of age, presented with acute onset dyspnoea. Radiography showed a diffuse
      pulmonary infiltrate throughout both lungs. Haematological abnormalities were an
      absolute neutrophilia and eosinophilia. Postmortem examination revealed uniform
      consolidation of both lungs which was defined histologically as a verminous
      granulomatous pneumonia. Metastrongyle larvae, isolated from the pulmonary
      tissue, had the morphological characteristics of Filaroides species. On the basis
      of the pathological changes and the larval morphology, a presumptive diagnosis of
      F hirthi pneumonia was made. This is believed to be the first report of disease
      due to this parasite in Ireland.

PMID- 9179821
TI  - Cystic thymoma in a cat with cholesterol-rich fluid and an unusual
      ultrasonographic appearance.
AB  - A cystic thymoma was identified in an eight-year-old domestic longhair cat with a
      chronic cough. Radiographs indicated a large mass of soft tissue density in the
      anterior thorax. Ultrasonography revealed an echogenic mass occupying the cranial
      and mid-thorax with a slight swirling movement of the echoes. Subsequent drainage
      under ultrasound guidance yielded a cholesterol-rich fluid. The mass was resected
      at exploratory thoracotomy and the diagnosis of thymoma confirmed. There was no
      sign of recurrence one year postoperatively. The clinical features and unusual
      laboratory findings are presented and compared with previously reported cases of
      thymomata in the cat.

PMID- 9179822
TI  - Helical CT for the detection of acute pulmonary embolism: experts debate.

PMID- 9179823
TI  - Acute pulmonary embolism: the role of computed tomographic imaging.

PMID- 9179824
TI  - Spiral CT of pulmonary embolism: technical considerations and interpretive
      pitfalls.
AB  - The diagnostic work-up of pulmonary embolism has been recently modified by the
      introduction of spiral computed tomography (CT), which enables noninvasive
      depiction of endoluminal clots in second-to fourth-division pulmonary arteries.
      If this technique is currently considered a powerful imaging alternative for the
      detection of acute central emboli, it is mainly related to the possibility to
      obtain a uniform and high degree of arterial enhancement of pulmonary arteries
      down to 2-3 mm in diameter. Minimal experience in spiral CT angiography is
      necessary to achieve this goal and requires familiarity with both data
      acquisition and contrast medium injection. A number of interpretive pitfalls
      exist in assessing spiral CT images, and certain caveats have to be heeded.
      However, it is important to keep in mind that their recognition becomes less and
      less problematic as the radiologist gains experience with spiral CT of the
      pulmonary vasculature. Therefore, the purpose of this article is to review the
      diagnostic approach to pulmonary embolism with spiral CT, with special emphasis
      on protocol parameters and scan interpretation.

PMID- 9179825
TI  - Spiral CT of pulmonary hypertension and chronic thromboembolism.
AB  - Pulmonary hypertension caused by chronic pulmonary embolism (PE) represents an
      uncommon, but severe and surgically curable complication of recurrent acute
      embolism. Because clinical signs might be silent or nonspecific, chronic PE
      requires imaging methods for diagnosis and treatment planning. Chest radiographic
      findings are usually nonspecific. Scintigraphy provides a high sensitivity for
      PE, but lacks anatomic resolution and sufficient specificity. Pulmonary
      angiography, albeit accurate, is an invasive procedure associated with low but
      still considerable morbidity and mortality. Thus, noninvasive methods are
      required. Most reliably in the diagnosis of acute and chronic PE, fast computed
      tomography (CT) techniques like spiral CT provide noninvasive means to detect and
      differentiate organized mural thrombi, as well as perfusion abnormalities and
      concomitant findings. Magnetic resonance imaging offers morphologic as well as
      functional information on lung perfusion and right heart function, but image
      quality needs improvement to be comparable with spiral CT. Thus, although spiral
      CT is recommended as the screening method for acute and chronic PE, magnetic
      resonance imaging might be the method of the future.

PMID- 9179826
TI  - Helical CT angiography of the thoracic aorta.
AB  - Five years after its introduction (11,36), spiral or helical CTA is being
      embraced as an important noninvasive tool for imaging the thoracic aorta and its
      branches. The high degree of accessibility and ease with which the studies are
      performed make it a viable alternative to aortography in the acute setting. Once
      the examiner is familiar with the principles of CTA, the acquisition phase of the
      examination can be completed in as little as 15 minutes, but it is critical that
      a thorough understanding of these principles guide the radiologist to maximize
      information gained by the technique. Several important challenges remain for CTA.
      First, the proliferation of image-processing workstations and software is
      improving our ability to exploit these CT data by allowing us to visualize them
      in novel ways (37) and create alternative renderings with greater ease and speed.
      Before relying on these alternative visualization techniques, their accuracy and
      pitfalls, and the incremental gain they achieve over interpretation of the
      primary transverse sections must be fully established. This requires that
      carefully designed studies with multiple blinded and independent reviewers
      isolate interpretative variations based on rendering technique alone, and not a
      combination of rendering and acquisition techniques where variables readily are
      confounded (38). Second, more investigators must step forward with results of the
      clinical utility of CTA to triage patients appropriately and direct medical and
      surgical therapy. Although well designed prospective comparisons of imaging
      examinations and measurement of patient outcomes are challenging to implement,
      they are critical to the rational selection of appropriate diagnostic tests. This
      is particularly true for the application of helical CTA to imaging of the
      posttraumatic aortic and aortic dissection. Finally, helical CT technology is far
      from static. Every year, new advances in engineering bring better image quality,
      improved resolution, and faster scan times. As medical imagers, we must not
      become complacent, but rather constantly challenge ourselves to consider how we
      might further improve on our use of CT equipment to maximize the collection of
      information relevant to diagnosis and therapy.

PMID- 9179827
TI  - Severity assessment of acute pulmonary embolism with spiral CT: evaluation of two
      modified angiographic scores and comparison with clinical data.
AB  - Spiral computed tomography (CT) has shown promising results in the detection of
      acute pulmonary embolism. The aim of this study was to investigate whether the
      severity of acute pulmonary embolism could be quantitatively assessed with spiral
      CT examinations and to test the potential clinical impact of this information. In
      a consecutive series of 123 patients screened with spiral CT for suspected acute
      pulmonary embolism, 31 patients (25%) had evidence of emboli. The severity of
      pulmonary arterial obstruction in those 31 spiral CT examinations was evaluated
      by two independent observers using angiographic scores previously described by
      Walsh (29) and Miller (30), adapted to the needs of spiral CT. Clinical patient
      subgroups were defined according to oxygen saturation, heart rate, and
      echocardiographic signs of right ventricular strain. CT severity scores were then
      correlated to each other and to clinical parameters using the Spearman rank test.
      Interobserver agreement was calculated using the analysis of variance. Both
      modified Walsh and Miller scores were readily reproducible and showed
      interobserver agreements of 0.85 and 0.96, respectively (p = 0.001). Patients
      with mild and marked clinical abnormalities showed statistically significant
      differences between CT severity scores. Differences between severity scores of
      patients with moderate and marked clinical abnormalities were somewhat
      significant. No significant mean severity score differences were seen between
      patients with mild and moderate clinical abnormalities. Although correlations of
      severity scores and detailed clinical parameters within the defined subgroups
      were moderate to poor, threshold scores greater than 10 (Miller) and greater than
      11 (Walsh) always indicated marked clinical abnormalities. The modified scores
      presented in this study constitute a readily reproducible method for the
      quantitative assessment of acute pulmonary embolism severity on spiral CT
      examinations.

PMID- 9179828
TI  - Sexual dimorphism in the age changes of the pituitary lactotrophs in rats.
AB  - It is known that aging is associated with alterations in hypothalamic and
      pituitary functions. In the present study, we have undertaken a quantitative
      immunohistochemical assessment of the lactotroph cell population as well as
      prolactin (PRL) secretion, in male and female rats of different ages. Pituitaries
      from young (3 months), old (20 months) and senescent (29 months) male and female
      Sprague-Dawley rats were processed for the immunohistochemical detection of
      lactotrophs. Serum PRL was measured by a homologous RIA. Additionally, the in
      vitro PRL secretory activity was estimated by perifusion of pituitary cells from
      senescent animals. Analysis of morphometric parameters revealed age-related
      changes of PRL cell population in animals of both sexes. The cell density (CD),
      surface density (SD) and volume density (VD) decreased with age in both male and
      female rats. However, CD as well as SD appeared to have increased in females when
      compared to males, either in young or old animals, while VD was higher only in
      old females. The pituitaries of senescent females displayed chromophobic
      microadenomas on a background of diffuse PRL cell hyperplasia. Prolactin serum
      levels showed a marked increase with age in females, but only a modest elevation
      in males. In senescent females, PRL production per cell was reduced. We conclude
      that in rats, there exists a clear sexual dimorphism in the age-related changes
      of pituitary PRL cells.

PMID- 9179829
TI  - The effect of aging on the immune response: influence of phosphatidylcholine
      containing lipid on IgD-receptor expression and antibody formation.
AB  - It was reported previously that IgD-receptors (IgD-R) are expressed on both CD4+
      and CD8+ human T cells and CD4+ murine T cells after exposure to oligomeric IgD,
      certain cytokines, or various pharmacological agents, as shown by rosetting with
      IgD-coated erythrocytes. Enhancement of antibody production is observed in mice
      after injection of oligomeric IgD and is mediated by these IgD-R+ T cells, while
      injection of monomeric IgD inhibits both IgD-R upregulation and augmentation of
      antibody responses induced by simultaneously injected oligomeric IgD. The effects
      of oligomeric IgD on IgD-R upregulation are lacking in aged mice. However, the
      oligomeric IgD induced enhanced antibody production can be transferred to aged
      mice with IgD-R+ T cells from young donors suggesting that the environment of the
      aged mouse supports the effector function of IgD-R+ T cells. We now report, in
      addition, that exposure to phosphatidylcholine (PC) and a PC-containing lipid
      mixture, AL721, is effective in causing IgD-R upregulation on T cells from both
      young and aged mice, and young humans. This effect can also be demonstrated in
      mice in vivo after administration of AL721. Moreover, this agent causes a two
      fold enhancement of antibody production, as measured by PFC/spleen, to 4-hydroxy
      5-iodo-3-nitrophenyl(acetyl)-Brucella abortus (NIP-BA) and NIP-horse red blood
      cells (RBC) in young and aged mice. There is no difference in the baseline
      membrane fluidity of lymphocytes from aged and young mice. Although PC causes an
      increase in membrane fluidity of lymphocytes from both young and old mice, and
      from humans, this effect on fluidity is not prevented by a protein kinase
      inhibitor, while PC's effect on IgD-R upregulation is prevented by the inhibitor.
      Moreover, no correlation was observed between IgD-R upregulation and membrane
      fluidity changes induced by AL721 administered in vivo. To evaluate the role of
      IgD-R induction in the augmentation of antibody production by phospholipids, the
      effect of monomeric IgD was investigated. The augmenting effect of AL721 on
      antibody production was prevented by a single injection of monomeric IgD at the
      time of antigen administration. We conclude that (1) PC-containing lipid mixtures
      are effective in enhancing antibody production in aged mice, (2) induction of IgD
      R is responsible for the augmenting effects of AL721 on antibody production, and
      (3) monomeric IgD not only blocks the upregulation of IgD-R, as shown previously,
      but also the augmenting effect of previously upregulated IgD-R on T cells by
      preventing their interaction with surface IgD+ B cells.

PMID- 9179830
TI  - Influence of dietary restriction on ionotropic glutamate receptors during aging
      in C57B1 mice.
AB  - The present study was designed to determine whether the memory sparing effects of
      dietary restriction during aging could be through an effect on ionotropic
      glutamate receptors. Quantitative autoradiography was performed on 3, 10, and 26
      month old mice to examine the density changes of NMDA, AMPA and kainate binding
      sites in aging animals. Spatial memory performance was also tested in these mice
      with the use of the Morris water maze. The 10 and 26 month olds were either ad
      libitum-fed or diet-restricted (60% of ad libitum-fed calories). Ad libitum-fed,
      26 month old mice had significant decreases in NMDA-displaceable [3H]glutamate in
      all ten cortical, two out of seven hippocampal, and two out of four subcortical
      regions, as compared to 3 month olds. Diet-restricted, 26 month old mice only
      differed significantly from young in three cortical and two subcortical regions.
      The aged ad libitum-fed mice exhibited significantly poorer performance in the
      spatial memory task than all other groups. The diet-restricted 26 month olds only
      performed significantly worse than 3 month olds and diet-restricted 10 month
      olds. These results suggest that some of the memory sparing effects of dietary
      restriction on aged animals may be due to an influence on NMDA receptors.

PMID- 9179831
TI  - Application of information technology in clinical diabetes care--a special issue.
      Part 1. Databases, algorithms and decision support.

PMID- 9179832
TI  - DIABCARD--an application of a portable medical record for persons with diabetes.
AB  - The medical record is central to the management of patients. For people with a
      chronic disease their many records, held at different locations, often pose a
      problem. Electronic patient records have been discussed for a long time. This
      article reports on the paradigm of a portable computer-based patient record on a
      smart card. It describes the development of the chip card based medical
      information system for chronic diseases in ambulatory and hospital care. The
      system has been implemented, tested and evaluated. DIABCARD could demonstrate
      that for a speciality patient record the capacity and functionality of the
      existing card is sufficient. Finally, the perspectives of chip cards in health
      care are discussed.

PMID- 9179833
TI  - Telemedicine for diabetes care: the DIABTel approach towards diabetes telecare.
AB  - Telemedicine is modifying classical health care by providing effective solutions
      to an increasing number of new situations. This article summarizes the potential
      benefits made available by this technology in diabetes care, and describes in
      detail how the new DIABTel Telemedicine Service complements the daily care of
      diabetic patients. The basic functions of the telemedicine system include
      telemonitoring of patient's blood glucose data and self-management actions, and
      remote care from doctors to diabetic patients. The system's architecture
      comprises two main components: the Medical Workstation, a PC-based system to be
      used by physicians and nurses in Diabetes Day Centre units in hospitals, and the
      Patient Unit, a palmtop-computer to be used by patients in their day to day
      activities. Both components, in an integrated approach, offer tools to doctors
      and patients for data collection and management, viewing and interpretation
      modules, data/message exchange services and an interactive glucose/insulin
      simulator for educational purposes. The DIABTel telemedicine diabetes care
      procedure aims: (1) to improve communication of the patient with the hospital
      based diabetologist, in between the patient's visits to the clinic; (2) to allow
      doctors to assess the patient's condition on a frequent basis (every week); (3)
      to help patients with management in the daily care of diabetes, and (4) to
      provide patients with a service of 'supervised autonomy', to increase patient's
      independence without decreasing the necessary continual support and supervision
      from the doctor. Finally, we discuss the practical problems, limitations and
      vital issues regarding implementation of the telemedicine service.

PMID- 9179834
TI  - Diabetes intervention in the information age.
AB  - Sustained improvement in blood glucose control is the only treatment outcome
      which will reduce or eliminate the long term complications of diabetes mellitus.
      We have designed and evaluated an electronic information system which facilitates
      this task. The system is voice-interactive, physician directed and affords, to
      remote patients, 24 h access via touch-tone telephone. Accordingly, patients
      access the system each day to report self-measured blood glucose levels or
      hypoglycaemic symptoms together with dietary changes, planned exercise, stress,
      illness or other lifestyle events. In turn they receive immediate advice with
      respect to medication dosing changes, and other pertinent feedback. Preliminary
      system beta-testing for safety and efficacy was performed for one year in an open
      study of 204 patients derived from two independent, health-care environments.
      Among the two testing centres, over 60,000 telephone cells were received by the
      computer systems during the start-up year. Safety and efficacy expectations were
      met. In addition, prevalence of diabetes related crises (hyperglycaemia or
      hypoglycaemia) fell approximately 3-fold. Glycated haemoglobin fell significantly
      (1.0-1.3%) in patients actively using the system. In control groups of patients
      not actively using the system, there were no improvements in metabolic control
      while body weights were stable in all groups. The new system was safe and
      effective in our hands and empowered our health professionals to provide improved
      diabetes care.

PMID- 9179835
TI  - Randomized controlled pilot trial of a hand-held patient-oriented, insulin
      regimen optimizer.
AB  - A robust, hand-held, patient-oriented insulin regimen optimizer (POIRO) has been
      developed. Relevant information is entered by selecting appropriate items from
      choices displayed on a touch-sensitive screen rather than a conventional
      keyboard. All data items are recorded, together with their time and date of
      entry, and may be recalled at any time with glucose values displayed graphically
      to provide an overview of glycaemic control. When requested, an integral, hybrid,
      statistical and rule-based expert system program uses all available data to
      suggest an optimum insulin dose within physician determined, pre-set limits.
      POIRO has been formally evaluated in a randomized crossover pilot trial,
      comparing two 3 week periods with and without decision support, in six patients
      with type 1 diabetes. Mean (SE) pre-prandial blood glucose levels were
      significantly lower during the period when decision support was available (7.5
      (0.4) versus 8.9 (0.4) mmol/l, p = 0.015) with no increase in the frequency or
      severity of hypoglycaemia. The device, which was well received by the patients,
      may offer a relatively inexpensive method of providing expert diabetic advice at
      a distance. The persistence of improved glycaemic control, even after decision
      support was switched off, suggests the device could be used intermittently by
      patients and may have educational value.

PMID- 9179836
TI  - Insulin algorithms in the self-management of insulin-dependent diabetes: the
      interactive 'Apple Juice' program.
AB  - The 'Apple Juice' program is an interactive diabetes self-management program
      which runs on a lap-top Macintosh Powerbook 100 computer. The dose-by-dose
      insulin advisory program was initially designed for children with insulin
      dependent (type 1) diabetes mellitus. It utilizes several different insulin
      algorithms, measurement formulae, and compensation factors for meals, activity,
      medication and the dawn phenomenon. It was developed to assist the individual
      with diabetes and/or care providers, in determining specific insulin dosage
      recommendations throughout a 24 h period. Information technology functions
      include, but are not limited to automated record keeping, data recall, event
      reminders, data trend/pattern analyses and education. This paper highlights
      issues, observations and recommendations surrounding the use of the current
      version of the software, along with a detailed description of the insulin
      algorithms and measurement formulae applied successfully with the author's
      daughter over a six year period.

PMID- 9179837
TI  - UTOPIA: a consultation system for visit-by-visit diabetes management.
AB  - UTOPIA (UTilities for OPtimizing Insulin Adjustment) is a prototype computer
      system proposed to support home data analysis and therapy recommendations for the
      individual patient. The paper describes methods of analysis and their
      incorporation into an overall system design that matches the iterative practices
      at the physician-patient consultation from visit to visit. Four modules support
      home data display and comparison with clinical measurements; extraction of blood
      glucose trends and daily cycles using time series analysis, learning
      relationships between insulin adjustments and changes in time series patterns via
      a parametric, linear systems model; and advice generation by solving the linear
      equation for candidate insulin adjustments. Concepts and methods are placed in
      context, with a discussion of comparable and related research.

PMID- 9179838
TI  - DIABNET: a qualitative model-based advisory system for therapy planning in
      gestational diabetes.
AB  - An intelligent decision support system for the analysis of home monitoring data
      and therapy planning in gestational diabetes is presented. The paper describes
      the integration of qualitative and quantitative reasoning modules within the
      DIABNET advisory system. The system kernel is a qualitative model of the
      physiological processes involved in the glucose metabolism of this type of
      diabetic patient. A causal probabilistic network (CPN) has been used to represent
      the qualitative model in order to manage uncertain and missing monitoring data.
      The DIABNET inputs are the patient's available ambulatory monitoring data, and
      the output is a dietary and insulin therapy adjustment that includes initiation
      of insulin therapy, quantitative insulin dose changes and qualitative diet and
      schedule modifications. Over periods of up to seven days, monitoring data are
      analysed by the CPN to detect any diet or insulin therapy items which may require
      modification. The qualitative insulin needs are translated into a quantitative
      proposal in line with the characteristics of the patient and the modification
      strategies usually used by doctors. The first evaluation of the system has been
      accomplished, the encouraging results of which are also presented.

PMID- 9179839
TI  - Polypeptide chain release factors.
AB  - Newly synthesized polypeptide chains are released from peptidyl-tRNA when the
      ribosome encounters a stop signal on mRNA. Extra-ribosomal proteins (release
      factors) play an essential role in this process. Although the termination process
      was first discovered in the late 1960s, much of the mechanism has remained
      obscure. However, important steps have recently been made in both prokaryotic and
      eukaryotic organisms in unlocking the secrets of this vital stage in protein
      synthesis. In this review we summarize these advances and focus attention on the
      remaining areas of uncertainty, particularly with respect to the models that have
      been proposed for the action of the GTP-hydrolysing termination factors in
      prokaryotes and eukaryotes, i.e. RF3 and eRF3.

PMID- 9179840
TI  - Energy requirement for pullulanase secretion by the main terminal branch of the
      general secretory pathway.
AB  - The energy requirement for the second step in pullulanase secretion by the
      general secretory pathway was studied in Escherichia coli. In order to uncouple
      the two steps in the secretion pathway (across the cytoplasmic and outer
      membranes, respectively) and to facilitate kinetic analysis of secretion, a
      variant form of pullulanase lacking its N-terminal fatty acid membrane anchor was
      used. The transport of the periplasmic secretion intermediate form of this
      protein across the outer membrane was not inhibited by concentrations of sodium
      arsenate in excess of those required to reduce ATP levels to < or = 10% of their
      normal value. Pullulanase secretion was inhibited by the protonophore carbonyl
      cyanide m-chlorophenyl hydrazone at concentrations which were similar to those
      reported by others to be required to prevent solute uptake or the export and
      processing of preproteins across the cytoplasmic membrane, but which were in
      excess of those required to fully dissipate the proton-motive force and to reduce
      lactose uptake to a significant extent.

PMID- 9179841
TI  - The C-terminal domain of the secretin PulD contains the binding site for its
      cognate chaperone, PulS, and confers PulS dependence on pIVf1 function.
AB  - Related outer membrane proteins, termed secretins, participate in the secretion
      of macromolecules across the outer membrane of many Gram-negative bacteria. In
      the pullulanase-secretion system, PulS, an outer membrane-associated lipoprotein,
      is required both for the integrity and the proper outer membrane localization of
      the PulD secretin. Here we show that the PulS-binding site is located within the
      C-terminal 65 residues of PulD. Addition of this domain to the filamentous phage
      secretin, pIV, or to the unrelated maltose-binding protein rendered both proteins
      dependent on PulS for stability. A chimeric protein composed of bacteriophage f1
      pIV and the C-terminal domain of PuID required properly localized PulS to support
      phage assembly. An in vivo complex formed between the pIV-PulD65 chimera and PulS
      was detected by co-immunoprecipitation and by affinity chromatography.

PMID- 9179842
TI  - The nucleoside diphosphate kinase of Mycobacterium smegmatis: identification of
      proteins that modulate specificity of nucleoside triphosphate synthesis by the
      enzyme.
AB  - We report the purification and characterization of the enzyme nucleoside
      diphosphate kinase (Ndk) from Mycobacterium smegmatis. The N-terminus of the
      enzyme was blocked but an internal sequence showed approx. 70% homology with the
      same enzymes from Pseudomonas aeruginosa and Escherichia coli. immobilization of
      the mycobacterial nucleoside diphosphate kinase on a Sepharose 4 B matrix and
      passing the total cell extract through it revealed four proteins (P70, P65, P60,
      and P50, respectively) of M(r) 70 kDa, 65 kDa, 60 kDa and 50 kDa that were
      retained by the column. While the proteins of M(r) 70 kDa and 50 kDa modulated
      the activity of Ndk directing it towards GTP synthesis, the 60 kDa protein
      channelled the specificity of Ndk entirely towards CTP synthesis. The 65 kDa
      protein modulated the specificity of Ndk directing it entirely towards UTP
      synthesis. The specificity for such mycobacterial proteins towards NTP synthesis
      is retained when they are complexed with P. aeruginosa Ndk. We further
      demonstrate that the P70 protein is pyruvate kinase and that each of the four
      proteins forms a complex with Ndk and alters its substrate specificity. Given the
      ubiquitous nature of Ndk in the living cell and its role in maintaining correct
      ratios of intracellular nucleoside triphosphates, the implications of the
      occurrence of these complexes have been discussed in relation to the precursor
      pool for cell wall biosynthesis as well as RNA/DNA synthesis.

PMID- 9179844
TI  - Transcriptional regulation of the Yersinia pseudotuberculosis pH6 antigen adhesin
      by two envelope-associated components.
AB  - The Yersinia pseudotuberculosis pH6 antigen mediates haemagglutination and
      adhesion to cultured mammalian cells. The synthesis of pH6 antigen requires the
      products of the psaEFABC genes in both Yersinia pseudotuberculosis and
      Escherichia coli. In-frame deletion mutations of psaE and psaF caused defective
      haemagglutination. In contrast, we showed that the psaABC genes were sufficient
      for haemagglutination if they were expressed by a heterologous promoter.
      Environmental regulation of pH6 antigen by temperature and pH occurs via
      regulation of the major pilus protein PsaA at the transcriptional level. Northern
      blot analyses indicate that the psaA transcript was absent in either psaE or psaF
      mutant strains. Primer extension analyses indicate that, in Y.
      pseudotuberculosis, the transcription of the psaE and psaF genes is constitutive.
      Alkaline phosphatase fusion studies confirm the topology prediction that PsaE and
      PsaF are both inner-membrane-associated proteins. PsaE consists of an N-terminal
      cytoplasmic domain, containing sequence similarity to transcriptional regulators
      found in two-component systems as well as to the Salmonella typhimurium HIIA
      protein, with a C-terminal domain that is periplasmically localized. PsaF is
      predicted to be oriented with most of the protein in the periplasm, the
      hydrophobic N-terminus being either integrated in the inner membrane or cleaved
      as a signal peptide.

PMID- 9179843
TI  - Structural basis for differential receptor binding of cholera and Escherichia
      coli heat-labile toxins: influence of heterologous amino acid substitutions in
      the cholera B-subunit.
AB  - The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat
      labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB
      can also bind to additional glycolipids and glycoproteins. A number of mutant CT
      B-subunits were generated by substituting CTB amino acids with those at the
      corresponding positions in LTB. These were used to investigate the influence of
      specific residues on receptor-binding specificity. A mutated CTB protein
      containing the first 25 residues of LTB in combination with LTB residues at
      positions 94 and 95, bound to the same extent as native LTB to both delipidized
      rabbit intestinal cell membranes, complex glycosphingolipids
      (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1
      intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in
      the 1-25 region were combined with those in the 75-83 region, a binding as strong
      as that of LTB to intestinal glycosphingolipids was observed. In addition, a
      mutant LTB with a single Gly-33-->Asp substitution that completely lacked
      affinity for both GM1 and non-GM1 glycosphingolipids could still bind to
      receptors in the intestinal cell membranes and to polyglycosylceramides. We
      conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and
      non-sialylated glycoconjugates, and that the binding to either class of receptors
      is influenced by different amino acid residues within the protein.

PMID- 9179845
TI  - Action at a distance for glp repressor control of glpTQ transcription in
      Escherichia coli K-12.
AB  - The adjacent, divergently transcribed glpACB and glpTQ operons of Escherichia
      coli encode the anaerobic glycerol 3-phosphate dehydrogenase and glycerol 3
      phosphate transporter/phosphodiesterase, respectively. These operons are
      negatively controlled by glp repressor binding to operators that overlap the glpA
      promoter elements. Using DNase I footprinting, three additional operators (OT1-3)
      were identified at positions +307 to +359 within the glpT coding region. To
      assess a potential regulatory role for these remote operators in vivo, a glpT
      lacZ transcriptional fusion containing all of the glpA and glpT operators was
      constructed. The response of this fusion to the glp repressor was compared to
      fusion constructs in which OT1 and OT3 were inactivated, either by deletion or by
      site-directed mutagenesis. It was found that repression of glpT conferred by
      binding of glp repressor to glpA operators was increased about three- to fourfold
      upon introduction of the remote glpT operators. In addition, two integration host
      factor (IHF) binding sites were identified downstream of the glpT transcriptional
      start site at positions +15 to +51 and +193 to +227. A regulatory role for IHF
      was demonstrated by showing that repression of glpT mediated by GlpR was
      decreased about twofold in strains deficient in IHF and that mutations in IHF1
      and/or IHF2 decreased repression about two- to threefold. The effect of IHF was
      apparent only when the remote operators were present. All of the results are
      consistent with a model of repression involving GlpR binding simultaneously to
      the glpA and remote glpT operators, with intervening DNA forming a loop.

PMID- 9179846
TI  - Ffh and FtsY in a Mycoplasma mycoides signal-recognition particle pathway: SRP
      RNA and M domain of Ffh are not required for stimulation of GTPase activity in
      vitro.
AB  - Mycoplasma mycoides contains a signal-recognition particle (SRP) composed of an
      RNA molecule and an SRP54 homologue (Ffh). We have now identified a mycoplasma
      homologue to the alpha subunit of the mammalian SRP receptor and Escherichia coli
      FtsY. The protein (MmFtsY) was expressed in E. coli and purified to homogeneity.
      MmFtsY has a weak intrinsic GTPase activity but GTP hydrolysis was markedly
      stimulated when it was combined with mycoplasma Ffh (MmFfh) and SRP RNA. Also, in
      the absence of SRP RNA GTPase activity was significantly enhanced. Furthermore,
      GTP hydrolysis was stimulated when MmFtsY was combined with the N-terminal GTPase
      domain (N+G) of MmFfh. These findings indicate that basic features of the GTPase
      activation mechanism are independent of the C-terminal M domain of the MmFfh
      protein. We propose that the activation is mediated to a large extent by contacts
      between the GTPase domains of the mycoplasma Ffh and FtsY proteins and that the
      contribution of the M domain and SRP RNA in the activation mechanism is mainly
      for modifying the conformation of the MmFfh GTPase domain.

PMID- 9179847
TI  - Sequence requirements for the termination of rolling-circle replication of
      plasmid pT181.
AB  - Most small multicopy plasmids of Gram-positive bacteria and many in Gram-negative
      bacteria replicate by a rolling-circle (RC) mechanism. The replication initiator
      proteins encoded by the RC plasmids and single-stranded bacteriophages of
      Escherichia coli have origin-specific nicking-closing activities that are
      required for the initiation and termination of RC replication. We have
      investigated the sequence requirements for termination of RC replication of
      plasmid pT181. The initiator nick site is located in the loop of a hairpin region
      (IRII) within the pT181 origin of replication. By mutational analysis, we have
      found that several nucleotides within the stem of IRII which are critical for the
      initiation activity are dispensable for termination of replication. We also
      demonstrate that nucleotides in the right arm of IRII, but not the left arm, are
      absolutely required for termination of RC replication. We have also identified
      specific nucleotides in IRII that are critical for its termination activity. The
      sequence of the right arm of the hairpin must be located downstream of the
      initiator nick site for termination, suggesting that termination requires a
      specific orientation of the initiator protein at the origin.

PMID- 9179848
TI  - Isolation and characterization of the mycobacterial phagosome: segregation from
      the endosomal/lysosomal pathway.
AB  - Mycobacteria have the ability to persist within host phagocytes, and their
      success as intracellular pathogens is thought to be related to the ability to
      modify their intracellular environment. After entry into phagocytes, mycobacteria
      containing phagosomes acquire markers for the endosomal pathway, but do not fuse
      with lysosomes. The molecular machinery that is involved in the entry and
      survival of mycobacteria in host cells is poorly characterized. Here we describe
      the use of organelle electrophoresis to study the uptake of Mycobacterium bovis
      bacille Calmette Guerin (BCG) into murine macrophages. We demonstrate that live,
      but not dead, mycobacteria occupy a phagosome that can be physically separated
      from endosomal/lysosomal compartments. Biochemical analysis of purified
      mycobacterial phagosomes revealed the absence of endosomal/lysosomal markers LAMP
      1 and beta-hexosaminidase. Combining subcellular fractionation with two
      dimensional gel electrophoresis, we found that a set of host proteins was present
      in phagosomes that were absent from endosomal/lysosomal compartments. The
      residence of mycobacteria in compartments outside the endosomal/lysosomal system
      may explain their persistence inside host cells and their sequestration from
      immune recognition. Furthermore, the approach described here may contribute to an
      improved understanding of the molecular mechanisms that determine the
      intracellular fate of mycobacteria during infection.

PMID- 9179849
TI  - A novel regulatory system required for pathogenicity of Xanthomonas campestris is
      mediated by a small diffusible signal molecule.
AB  - Mutations in the seven clustered rpf genes cause downregulated synthesis of
      extracellular enzymes and reduced virulence of Xanthomonas campestris pathovar
      campestris (Xcc). The phenotype of mutants in one of the genes, rpfF, can be
      restored by a diffusible extracellular factor (DSF) produced by all Xcc strains
      tested, apart from rpfF and rpfB mutants. DSF accumulates in early stationary
      phase (when synthesis of enzymes is maximal), but levels decline subsequently.
      Addition of DSF to exponentially-growing wild-type bacteria does not cause
      precocious enzyme synthesis. rpfB and rpfF are expressed throughout growth, but
      the rate increases in early stationary phase. RpfB is predicted to be a long
      chain fatty acyl CoA ligase, and RpfF shows some relatedness to enoyl CoA
      hydratases. The properties of DSF suggest that it may be a fatty-acid derivative,
      and certain lipid preparations possess DSF activity at higher concentrations.
      These include lipid extracts and acid-hydrolysed lipoplysaccharide and lipid A
      from Xcc, and purified dodecanoic and hydroxydodecanoic acid. DSF production is
      confined to certain xanthomonads. We propose a model for the DSF system, which
      represents a novel mechanism for regulating virulence factor synthesis in
      response to physiological or environmental changes.

PMID- 9179850
TI  - Modulator protein RsbR regulates environmental signalling in the general stress
      pathway of Bacillus subtilis.
AB  - Bacillus subtilis responds to signals of environmental and metabolic stress by
      inducing over 40 general stress genes under the control of the sigma B
      transcription factor. sigma B activity is regulated post-translationally by a
      multi-component network composed of two coupled partner-switching modules, RsbX
      RsbS-RsbT and RsbU-RsbV-RsbW, each containing a serine phosphatase (X or U), an
      antagonist protein (S or V), and a switch protein/serine kinase (T or W). The
      upstream module (X-S-T) is required to transmit signals of environmental stress.
      In contrast, the downstream module (U-V-W) is required to transmit signals of
      energy stress as well as the environmental signals conveyed to it from the
      upstream module. Until now the function of the rsbR gene product was unknown.
      RsbR shares significant sequence similarity with the RsbS and RsbV antagonist
      proteins whose phosphorylation states control key protein-protein interactions
      within their respective modules. Here we present evidence that RsbR is associated
      with RsbS in the upstream, environmental-sensing module. To investigate RsbR
      function, we constructed deletion and point mutations within rsbR and tested
      their effects on expression of sigma B-dependent reporter fusions, both singly
      and in combination with other rsb mutations. To determine the possible
      interaction of RsbR with other Rsb proteins, we tested the ability of wild-type
      or mutant RsbR to activate transcription in the yeast two-hybrid system in
      conjunction with other Rsb regulators. On the basis of this genetic analysis, we
      conclude that RsbR is a positive regulator which modulates sigma B activity in
      response to salt and heat stress. Our data further suggest that: (i) RsbR
      influences the antagonist function of RsbS by direct protein-protein interaction;
      and (ii) this interaction with RsbS is likely controlled by the phosphorylation
      state of RsbR.

PMID- 9179851
TI  - The cioAB genes from Pseudomonas aeruginosa code for a novel cyanide-insensitive
      terminal oxidase related to the cytochrome bd quinol oxidases.
AB  - The structural genes for the cyanide-insensitive terminal oxidase (CIO) of
      Pseudomonas aeruginosa were sequenced. The locus comprised two open reading
      frames, cioA and cioB, coding for gene products of 488 and 335 amino acid
      residues with predicted molecular masses of 54241 and 37016 Da respectively.
      These genes were encoded by a 2.7 kb transcript and probably comprise an operon.
      Upstream of a major transcriptional start site is a -10 promoter region and,
      approximately at nucleotides -50 and +13, there are sequences homologous to the
      binding site of the transcriptional regulator Anr. The deduced amino acid
      sequences of CioA and CioB are homologous to the cytochrome bd quinol oxidases of
      Escherichia coli and Azotobacter vinelandii. However, no cytochrome d-like
      signals were found in wild-type P. aeruginosa strains. An atypical cytochrome d
      like signal was seen under low-aeration growth conditions but only in strains in
      which the cioAB genes were present on a high-copy-number plasmid. The appearance
      of these cytochrome d-like signals was not paralleled by a concomitant increase
      in CIO activity. These data support the hypothesis that the CIO of P. aeruginosa
      does not contain haem d. This raises the possibility that there is a family of
      bacterial quinol oxidases related to the cytochrome bd of E. coli that can differ
      in their haem composition from the E. coli paradigm.

PMID- 9179852
TI  - HlyX, the FNR homologue of Actinobacillus pleuropneumoniae, is a [4Fe-4S]
      containing oxygen-responsive transcription regulator that anaerobically activates
      FNR-dependent class I promoters via an enhanced AR1 contact.
AB  - The hlyX gene of the pig pathogen Actinobacillus pleuropneumoniae encodes HlyX, a
      homologue of FNR, the anaerobic transcription regulator of Escherichia coli. The
      hlyX gone complements the anaerobic respiratory deficiencies of E. coli fnr
      mutants but also induces the expression of an otherwise latent haemolysin.
      Therefore, FNR and HlyX have distinct but overlapping regulons. The hlyX gene has
      been overexpressed as a gst::hlyX fusion and the HlyX protein purified. Similar
      to FNR, HlyX can acquire a [4Fe-4S] cluster, which promotes binding to the FNR
      box (Kd of 20-30 nM) under anaerobic conditions. Expression of hlyX in E. coli
      induced the anaerobic production of at least five polypeptides, including the
      yfiD gene product, which were not induced by fnr. Analysis of the yfiD promoter
      region revealed the presence of two FNR boxes situated at -61.5 and -114.5.
      Consistent with this observation, expression from the semi-synthetic Class I
      promoter FF + 20pmelR was efficiently activated by HlyX but not by FNR. The
      weaker level of FNR-mediated activation of Class I promoters suggests that there
      is a poorer activating contact (activating region 1 (AR1) equivalent) between FNR
      and RNA polymerase at these promoters and that HlyX possesses an additional or
      improved AR1. The AR1 of HlyX is partially characterized by a surface-exposed
      region around amino acid A187, which confers the altered specificity and provides
      an explanation for the existence of distinct but overlapping HlyX and FNR
      regulons.

PMID- 9179853
TI  - A C-terminal di-leucine motif and nearby sequences are required for NH4(+)
      induced inactivation and degradation of the general amino acid permease, Gap1p,
      of Saccharomyces cerevisiae.
AB  - The general amino acid permease, Gap1, of Saccharomyces cerevisiae is very active
      in cells grown on proline as the sole nitrogen source. Adding NH4+ to the medium
      triggers inactivation and degradation of the permease via a regulatory process
      involving Npi1p/Rsp5p, a ubiquitin-protein ligase. In this study, we describe
      several mutations affecting the C-terminal region of Gap1p that render the
      permease resistant to NH4(+)-induced inactivation. An in vivo isolated mutation
      (gap1pgr) causes a single Glu-->Lys substitution in an amino acid context similar
      to the DXKSS sequence involved in ubiquitination and endocytosis of the yeast
      alpha-factor receptor, Ste2p. Another replacement, substitution of two alanines
      for a di-leucine motif, likewise protects the Gap1 permease against NH4(+)
      induced inactivation. In mammalian cells, such a motif is involved in the
      internalization of several cell-surface proteins. These data provide the first
      indication that a di-leucine motif influences the function of a plasma membrane
      protein in yeast. Mutagenesis of a putative phosphorylation site upstream from
      the di-leucine motif altered neither the activity nor the regulation of the
      permease. In contrast, deletion of the last eleven amino acids of Gap1p, a region
      conserved in other amino acid permeases, conferred resistance to NH4+
      inactivation. Although the C-terminal region of Gap1p plays an important role in
      nitrogen control of activity, it was not sufficient to confer this regulation to
      two NH4(+)-insensitive permeases, namely the arginine (Can1p) and uracil (Fur4p)
      permeases.

PMID- 9179854
TI  - Characterization of the negative elements involved in silencing the bgl operon of
      Escherichia coli: possible roles for DNA gyrase, H-NS, and CRP-cAMP in
      regulation.
AB  - The bgl operon of Escherichia coli is rendered cryptic and uninducible in wild
      type cells by the presence of DNA structural elements that negatively regulate
      transcription. We have carried out a detailed analysis of the sequences
      implicated in negative regulation. Fine-structure deletion analysis of the
      upstream sequences showed the presence of at least two elements involved in
      silencing the promoter. Chemical probing of genomic DNA in vivo showed that a
      region of dyad symmetry, present upstream of the promoter, is hypersensitive to
      KMnO4. The hypersensitive region detected corresponds to the potential cruciform
      structure implicated earlier in negative regulation. Enhancement of transcription
      from the wild-type promoter, observed in the presence of the gyrase inhibitor
      novobiocin, was absent in a mutant that carried point mutations in the inverted
      repeat. This observation suggests that the activation seen in a gyrase mutant is
      mediated by destabilization of the cruciform because of reduced supercoiling.
      Deletion of sequences downstream of the potential cruciform also resulted in an
      increase in transcription, indicating the presence of a second regulatory
      element. Measurement of transcription from the bgl promoter carrying the
      deletion, in a strain that has a mutation in the hns gene, indicated that this
      region is likely to be involved in binding to H-NS or a protein regulated by H
      NS, which acts as a non-specific repressor. We also provide evidence which
      suggests that transcriptional activation by mutations at the cAMP receptor
      protein (CRP)-binding site is mediated partly by antagonization of the negative
      effect of H-NS by CRP-cAMP as a result of its increased affinity for the mutant
      site.

PMID- 9179855
TI  - Transcriptional regulation of the macrophage-induced gene (gspA) of Legionella
      pneumophila and phenotypic characterization of a null mutant.
AB  - Expression of the global stress protein gene (gspA) is induced during the
      intracellular infection of macrophages and upon exposure of Legionella
      pneumophila to in vitro stress stimuli. Transcription of gspA is regulated by two
      promoters, one of which is regulated by the sigma 32 heat-shock transcription
      factor. We utilized a gspA promoter fusion to a promoter less lacZ to probe the
      phagososmal 'microenvironment' for the kinetics of exposure of intracellular L.
      pneumophila to stress stimuli. Expression through the gspA promoter was
      constitutively induced by approx. 16-fold throughout the intracellular infection,
      and occurred predominantly through the sigma 32-regulated promoter. Expression of
      the gspA promoter was induced approx. 4.5-fold, 5-, 11- and 9-fold upon exposure
      of L. pneumophila to heat shock, oxidative stress, acid shock, and osmotic shock,
      respectively. An isogenic insertion mutant of L. pneumophila in gspA (strain
      AA224) was constructed by allelic exchange in the wild-type strain AA200.
      Compared to in vitro-grown wild-type strain AA200, AA224 was more susceptible to
      all four in vitro stress stimuli. The wild-type phenotypes were restored to
      strain AA224 by complementation with a plasmid containing wild-type gspA. There
      was no difference between the wild-type strain and the gspA mutant in
      cytopathogenicity to U937 cells or in their kinetics of intracellular replication
      within macrophages and amoebae. However, compared to in vitro-grown bacteria,
      macrophage-grown and amoebae-grown AA200 and AA224 showed an equal and dramatic
      increase in resistance to in vitro stress stimuli. Our data showed that
      regardless of the capacity of L. pneumophila to subvert the microbicidal
      mechanisms of the macrophage, intracellular L. pneumophila is exposed to a high
      level of stress stimuli throughout the intracellular infection. Although the GspA
      protein is required for protection of the bacteria against in vitro stress
      stimuli, and is induced during intracellular multiplication, the loss of its
      function is probably compensated for by other macrophage-induced and stress
      induced proteins within the intracellular environment.

PMID- 9179856
TI  - The sigma S level in starving Escherichia coli cells increases solely as a result
      of its increased stability, despite decreased synthesis.
AB  - The sigma S level in starving (stationary phase) Escherichia coli cells increases
      four-to sixfold following growth in a defined or a complex medium. Chemostat
      grown cells, subjected to increasing carbon starvation, also become progressively
      richer in sigma S content. These increases occur despite reduced transcription of
      the sigma S-encoding gene, rpoS, and translation of rpoS mRNA, and result solely
      from a large increase in the stability of the sigma protein. Previous results,
      based on rpoS::lacZ transcriptional and translational fusions, and on methionine
      incorporation in sigma S, had suggested increased synthesis of sigma S in
      starving cells. Alternative explanations for these results consistent with the
      conclusions of this paper are discussed.

PMID- 9179857
TI  - Analysis of the architecture of the transcription factor sigma N (sigma 54) and
      its domains by circular dichroism.
AB  - Enhancer-dependent transcription in bacteria requires the alternative
      transcription factor sigma N (sigma 54), which forms an RNA polymerase holoenzyme
      that binds promoters as a transcriptionally inactive complex. We have examined
      the structure of sigma N by circular dichroism (CD) analysis. The sigma N protein
      and its domains are well structured in the absence of the core RNA polymerase
      subunits or promoter DNA. Denaturation of sigma N by temperature as followed by
      changes in CD shows a concomitant loss of secondary and tertiary structures with
      a melting temperature of 36 degrees C. The secondary structure displays a two
      state melting curve with a second Tm of 85 degrees C. The amino-terminal Region I
      activation domain together with the acidic Region II does not contribute to the
      two-state melting. In marked contrast, the integrity of the C-terminal DNA
      binding domain is required for the two-state melting. Measurements of pKb also
      demonstrated that a C-terminal part of sigma N, but not regions I or I + II, is
      required for the structural integrity of sigma N at high pH. Measurements of pKa
      suggested that alpha-helical structures are important in sigma N for the
      establishment of tertiary structural elements. The tertiary structure near
      ultraviolet CD signals of sigma N do not require regions I or I + II but were
      strongly diminished by C-terminal truncation of sigma N. Promoter DNA binding
      resulted in a conformational change in sigma N, permitting the determination of a
      binding constant. A typical B-DNA conformation was adopted by the promoter DNA.
      Implications for the modular domain organization of sigma N, the function of C
      terminal sequences, and domain communication and its role in activation of
      transcription are discussed.

PMID- 9179858
TI  - Structure of the DNA-binding domain of the OmpR family of response regulators.

PMID- 9179859
TI  - Neisseria gonorrhoeae reverse transcriptase activity does not mediate pilin gene
      conversion.

PMID- 9179860
TI  - A quest for symbiosis-specific genes urges itself upon Rhizobium geneticists.

PMID- 9179861
TI  - Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus
      induced by kainic acid.
AB  - We have previously shown that dextromethorphan (DM) antagonizes kainic acid (KA)
      induced neurotoxicity. Accumulating evidence indicates that the induction of
      seizure activity causes profound alterations in the levels of hippocampal opioid
      peptide mRNA. The present study was performed to further explore the effect of DM
      on KA-induced seizures as measured by hippocampal opioid peptide mRNA levels.
      Both Northern blot and in situ hybridization methods were used to examine the
      proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the rat hippocampus.
      The robust seizure activity induced by KA correlated with a significant increase
      in hippocampal opioid peptide mRNA levels. Pretreatment of rats with DM decreased
      hippocampal PENK and PDYN mRNA levels and seizure activity induced by KA.
      Hippocampal PDYN mRNA levels fell quickly but PENK mRNA levels fell rather
      slowly, indicating that the PENK and PDYN mRNAs are differentially regulated. Our
      results demonstrate that DM modulates opioid peptide gene expression induced by
      KA, and that DM protects against KA-induced seizures.

PMID- 9179862
TI  - Luteinizing hormone-releasing hormone (LHRH) attenuates morphine-induced
      inhibition of cyclic AMP (cAMP) in opioid-responsive SK-N-SH cells.
AB  - SK-N-SH cells were used to assess the effects of luteinizing hormone-releasing
      hormone (LHRH) on opioid receptor-mediated changes in cyclic AMP (cAMP).
      Prostaglandin E1 (PGE1, 1 microM) caused a dramatic increase in cAMP levels.
      Treatment with 10 microM morphine (MOR) significantly inhibited the stimulatory
      effect of PGE1, LHRH (0.8 microM) caused an increase in the basal level of
      intracellular cAMP and potentiated the stimulatory effect of PGE1 on cAMP
      accumulation. In cells pretreated with LHRH the inhibitory effect of MOR on cAMP
      accumulation was significantly attenuated. An LHRH antagonist had no effect on
      cAMP. The involvement of pertussis toxin (PTX)-sensitive G proteins in the
      actions of LHRH was studied. PTX increased the stimulatory effect of PGE1 on cAMP
      and attenuated the inhibitory effect of MOR. However, PTX pretreatment prevented
      the effects of LHRH on the intracellular actions of PGE1 but exerted an additive
      effect with LHRH in blocking the MOR-induced decrease in cAMP levels. We conclude
      that LHRH attenuates the inhibitory, opioid receptor-mediated effect of MOR on
      intracellular cAMP accumulation in SK-N-SH cells, and that the G protein
      independent mechanism may be involved in LHRH-induced attenuation of the
      inhibitory effect of MOR on neuronal cAMP.

PMID- 9179863
TI  - Vasoactive intestinal peptide (VIP) induces IL-6 and IL-8, but not G-CSF and GM
      CSF release from a human bronchial epithelial cell line.
AB  - Vasoactive intestinal polypeptide (VIP) is a 28-amino acid neuropeptide with
      vasodilator, bronchodilator, and anti-inflammatory effects. Little is known about
      pro-inflammatory effects of VIP. We investigated the effect of VIP on the
      secretion of IL-6, IL-8, GM-CSF, and G-CSF from a bronchial epithelial cell line
      (BEAS 2B). The incubation of BEAS-2B cells with VIP in concentrations of 10(-13)
      to 10(-7) M for 4 h, caused dose-related increases of IL-6 (98% increase above
      control, P < 0.001) and IL-8 (35% increase above control, P < 0.01). After 4 h of
      incubation, 10(-7) M PHI also increased IL-6 release by 74% (P < 0.01). After 8 h
      of incubation, VIP increased IL-6 release by 59% (P < 0.01), causing no effect on
      IL-8 release. After 24 h of incubation, VIP increased the release of IL-6 by 48%
      (P < 0.05) and IL-8 by 45% (P < 0.05). Ribonuclease protection assays for steady
      state IL-6 mRNA revealed that increases in response to VIP stimulation occurred
      by 1 h and persisted through 16 h of stimulation. VIP had no significant effect
      on the release of G-CSF and GM-CSF. VIP did not induce cell proliferation at 24
      and 48 h. These findings suggest that VIP can alter epithelial cell cytokine
      release and might be capable of modulating the airway inflammatory response in
      this manner.

PMID- 9179864
TI  - The regulation of prodynorphin gene expression in cultured spinal cord cells:
      involvement of second messengers.
AB  - The regulation of prodynorphin (proDYN) mRNA levels by cAMP and protein kinase C
      (PKC) pathways was studied in cultured rat spinal cord cells. Spinal cord cells
      were cultured from 14 day (E 14) embryos of Sprague-Dawley rats. After 7 days in
      vitro, the spinal cord cells were incubated with either forskolin (5 microM) or
      phorbol-13-myristate acetate (PMA; 2.5 microM) for 1, 3, 6, 9, 12, or 24 h and
      the total RNA was isolated for Northern blot analyses. The proDYN mRNA level
      began to increase 1 h, then reached and remained at a peak 3-6 h after
      stimulation by forskolin or PMA. proDYN mRNA levels in forskolin treated cells
      decreased slightly from their peak after 9 h of treatment, whereas the level of
      proDYN mRNA returned to the basal level in PMA-treated cells. Pretreatment of
      cells with cycloheximide (a protein synthesis inhibitor; 10 microM) did not
      affect the forskolin- or PMA-induced increase in proDYN mRNA, but pretreatment
      with nimodipine (a L-type Ca2+ channel blocker; 2 microM), omega-conotoxin (a N
      type Ca2+ channel blocker; 1 microM), or KN-62 (a Ca2+/calmodulin-dependent
      protein kinase II inhibitor; 5 microM) inhibited induction of proDYN mRNA both by
      forskolin and PMA. Additionally, dexamethasone did not affect the expression of
      proDYN mRNA level induced by forskolin. Our results suggest that proDYN mRNA
      levels in spinal cord cells is regulated by both cAMP and PKC pathways. Calcium
      influx through both L- and N-type calcium channels and Ca2+/calmodulin-dependent
      protein kinase II appear to be involved in the increase of proDYN mRNA levels
      induced by either forskolin or PMA. Furthermore, ongoing protein synthesis is not
      required for forskolin- or PMA-induced responses.

PMID- 9179865
TI  - Exploring the expression of the melanin-concentrating hormone messenger RNA in
      the rat lateral hypothalamus after goldthioglucose injection.
AB  - Melanin-concentrating hormone (MCH) is expressed in a large neuronal population
      of the rat lateral hypothalamus. This area is known to be implicated in the
      regulation of thirst and hunger and to contain glucose-sensitive cells. In the
      present study, we investigated the effects of goldthioglucose (GTG), a toxic form
      of glucose, on the expression of the MCH gene in the rat lateral hypothalamus by
      immunocytochemistry, in situ hybridization and competitive RT-PCR. We observed
      that the MCH immunoreactivity and the level of MCH mRNA were not changed after
      intraperitoneal GTG injection (0.35 mg/g body weight). These results together
      with previous data suggest that the glucose-sensitive cells of the lateral
      hypothalamus are different from the MCH neurons and remain to be identified.

PMID- 9179866
TI  - Immunocytochemical demonstration of pituitary adenylate cyclase activating
      polypeptide (PACAP) in the porcine epiphyseal cartilage canals.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP), a member of the
      vasoactive intestinal polypeptide (VIP)/secretin/glucagon family, is known to be
      a powerful stimulator of adenylate cyclase. Recently, PACAP has been shown to
      stimulate cAMP in osteoblast-like cells and mouse calvarian bones. In the present
      study, PACAP immunoreactivity (IR) was demonstrated in cartilage canals from
      newborn and 3-4-week-old pigs. In tissues from the femoral head and the patella
      with and without ossification centres, PACAP-IR nerve fibres were found in the
      cartilage canals innervating blood vessels. The pattern of distribution was not
      dependent on age or the occurrence of an ossification centre. Co-localization
      studies showed a high degree of co-localization with calcitonin gene-related
      peptide (CGRP) and substance P (SP) but little co-localization with VIP. Our
      findings support earlier findings of CGRP, SP and VIP in bone tissue and add
      PACAP to the group of neuropeptides with a sensory and/or modulatory function in
      bone tissue.

PMID- 9179867
TI  - Changes in hypothalamic oxytocin levels during morphine tolerance.
AB  - The role of hypothalamic oxytocin neurons in the hypothalamus-pituitary-adrenal
      (HPA) axis adaptation during opioid tolerance has not been explored. In this
      study the modification of oxytocin levels in different hypothalamic nuclei was
      determined after acute or chronic morphine exposure. Male rats were implanted
      with placebo (naive) or morphine (tolerant) pellets for 7 days. On day 8, groups
      of rats received an acute injection of either saline i.p. or morphine (30 mg/kg
      i.p.) and were sacrificed 30 min later. In morphine-tolerant rats, there was a
      decrease in the oxytocin content in the median eminence (ME) and in the
      supraoptic nucleus (SO) after acute injection of saline or morphine. No
      modifications were seen in the paraventricular nucleus (PVN). The present study
      demonstrates that chronic morphine administration alters the brain oxytocin
      system, which suggests that this peptide might contribute to the behavioural,
      emotional and neuroendocrine responses to opioids.

PMID- 9179868
TI  - Investigation of inhibition angiotensin-converting enzyme (ACE) activity and
      opioid activity of two hemorphins, LVV-hemorphin-5 and VV-hemorphin-5, isolated
      from a defined peptic hydrolysate of bovine hemoglobin.
AB  - Two peptides, LVV-hemorphin-5 and VV-hemorphin-5, were isolated from a defined
      peptic bovine hemoglobin hydrolysate by reversed-phase HPLC. These peptides were
      identified as 31-38 and 32-38 fragments of beta chain of bovine hemoglobin. Their
      inhibitory activity towards angiotensin-converting enzyme and opioid potency were
      determined. Since their amino acid sequences show close homology with spinorphin,
      which is found in human cerebrospinal fluid and in the bovine spinal cord, the
      possible physiological role in vivo of these peptides was discussed.

PMID- 9179869
TI  - Detection of APGWamide-like immunoreactivity in the sea scallop, Placopecten
      magellanicus.
AB  - In pulmonate gastropods, the peptide, Ala-Pro-Gly-Trp-NH2 (APGWamide), appears to
      be located nearly exclusively in the neural circuitry controlling the male
      reproductive organs. This neuropeptide and related neuropeptides are also present
      and apparently bioactive in bivalve molluscs, although their physiological role
      in these latter animals is unknown. The present report uses immunohistochemistry
      to examine the distribution of APGWamide and/or related peptides within the
      tissues of the deep sea scallop, Placopecten magellanicus. Much of the APGWamide
      like immunoreactivity (APGWa-LIR) was detected in the central nervous system
      (CNS) of both juvenile and adult scallops, where it was concentrated in the
      cerebral, pedal and parietovisceral ganglia, particularly in the cortex of
      ganglionic cells and their axons which extend into the central neuropilar region.
      APGWa-LIR was also detected in the nerves ramifying from these ganglia. In
      addition, strong APGWa-LIR was localized in what appeared to be axonal terminals
      within peripheral tissues including the striated adductor muscle, foot, gills,
      labial palps, lips, tentacles and gonads of the juvenile scallops. The presence
      of APGWa-LIR was also confirmed in the gonads of adults of both sexes. Cursory
      examinations of the CNS of the mussel, Mytilus edulis, and the oyster,
      Crassostrea virginica, revealed the presence of APGWa-LIR in cell bodies and
      processes in these bivalve species as well. It is concluded that APGWamide and/or
      related peptides are probably important neurotransmitters and/or neuromodulators
      of several central and peripheral functions in P. magellanicus and other
      bivalves. Future work must focus on the possible roles for APGWamide in the
      physiological processes of these and other bivalve species.

PMID- 9179870
TI  - Bombesin-like peptide is present in duct cells in salivary glands: studies on
      normal and irradiated animals.
AB  - Bombesin (BN) and its mammalian counterpart gastrin-releasing peptide act as
      neuroregulatory hormones and tissue-specific growth factors, and have been
      implicated as peripheral and central satiety-inducing agents. In the present
      study, the immunohistochemical expression of BN in submandibular, sublingual and
      parotid glands of rats was examined 10 days after 5 consecutive days with daily
      doses of 6-8 Gy irradiation. Radioimmunoassay (RIA) methods were also used.
      Immunoreactive granular structures were observed within duct cells of both
      controls and irradiated animals. In the parenchyma of irradiated animals, very
      few nerve fibres showing BN-like immunoreactivity were observed. The RIA analysis
      showed that the content of BN-like material significantly increased in
      submandibular and parotid glands in response to irradiation. The results suggest
      that mainly a non-neural form of BN is detected in the salivary glands in the
      immunohistochemical analysis. Thus, the immunohistochemical observations suggest
      that BN-like peptides may be present in the duct system, where they may be
      constituents of the saliva. The observations of an increase in BN content in
      response to irradiation are of interest as BN has mitogenic effects, may
      stimulate secretion and contributes to satiety.

PMID- 9179871
TI  - Evidence for roles of vasoactive intestinal polypeptide (VIP) and pituitary
      adenylate cyclase activating polypeptide (PACAP) receptors in modulating the
      responses of rat dorsal horn neurons to sensory inputs.
AB  - The extracellularly recorded electrophysiological activity of single
      multireceptive dorsal horn neurons was markedly increased by ionophoretic
      administration of vasoactive intestinal polypeptide (VIP) or pituitary adenylate
      cyclase activating polypeptide (PACAP)-38. Some cells responded selectively to
      PACAP-38 (suggesting mediation by a PACAP receptor), whereas others responded to
      both VIP and PACAP-38 (suggesting a VIP1 and/or VIP2 receptor). Most non
      nociceptive cells were unaffected by PACAP-38 and all were unaffected by VIP. The
      selectivity of VIP/PACAP receptor antagonists was established on cloned rat VIP1,
      VIP2 and PACAP receptors in vitro before their utilization to indicate the likely
      involvement of VIP1, and possibly PACAP receptors, in VIP- and PACAP-38-mediated
      responses of dorsal horn neurons. The VIP/PACAP receptor antagonists inhibited
      responses of multireceptive cells to sustained innocuous (brush) and noxious
      (mustard oil) stimuli, with a selectivity suggesting the involvement of VIP1 and
      PACAP receptors, although the participation by VIP2 receptors cannot be excluded.
      These data implicate both VIP and PACAP in regulating the basal responsiveness of
      multireceptive dorsal horn neurons to sensory stimuli.

PMID- 9179872
TI  - Modulation of endothelin-induced intracellular Ca2+ mobilization by interleukin-1
      beta and lipopolysaccharide in C6 rat glioma cells.
AB  - We have investigated the effects of interleukin (IL)-1 beta and
      lipopolysaccharide (LPS) on endothelin (ET)-induced intracellular Ca2+ rise in C6
      rat glioma cells in order to study the mechanisms of their effects on Ca2+
      signaling systems. Pretreatment with IL-1 beta (10(3) U/mL) and LPS (1
      microgram/mL) for 24 h significantly inhibited 100 nM ET-1-induced increase in
      intracellular Ca2+ either in the presence or absence of external Ca2+. Their
      inhibitory effects were in dosedependent (IL-1 beta; 50-1000 U/mL, LPS; 10-1000
      ng/mL) and time-dependent (12-24 h) manners. A tyrosine kinase antagonist
      genistein (50 microM) but not a protein kinase C inhibitor H7 (30 microM)
      prevented the inhibition of the ET response by IL-1 beta and LPS. These results
      suggest that activation of tyrosine kinase may be essential for the inhibition of
      the ET receptor-mediated Ca2+ signaling systems by IL-1 beta and LPS.

PMID- 9179873
TI  - Activity of centrally truncated analogues of neuropeptide Y at Y1 and Y2 receptor
      subtypes in vivo.
AB  - Neuropeptide Y (NPY), a sympathetic cotransmitter, has both prejunctional and
      postjunctional actions in the cardiovascular system. In anaesthetized rats, the
      bioassay system used here, NPY attenuates cardiac vagal action (a prejunctional
      or Y2 action) and increases blood pressure (a postjunctional or Y1 action).
      Several NPY analogues were tested against NPY. In these, centrally located amino
      acid sequences of various lengths were removed, and replaced with simpler
      'spacers'. As the parent NPY molecule is considered to exist in a U-shape, these
      central truncations were intended to shorten the depth of the U, while
      maintaining the integrity of its two ends. The centrally truncated NPY analogues
      examined here retain activity at both receptor subtypes in vivo. These findings
      indicate that the U-shape of the parent molecule probably exists to assist
      stability, but that receptor binding occurs through sequences closer to the
      termini.

PMID- 9179874
TI  - Preprotachykinin A and cholecystokinin mRNAs in tenascin-gene knockout mouse
      brain.
AB  - Tenascin (TN), an extracellular matrix glycoprotein, exhibits various functions
      in the developmental stage of the mammalian brain. TN-gene deficient mice show
      abnormal behavior such as hyperlocomotion and poor swimming ability, and this
      abnormal behavior may derive from a low level of dopamine transmission in the
      striatum or hippocampus of the TN-gene disrupted mouse brain. We assayed
      preprotachykinin A (PPT) and cholecystokinin (CCK) mRNAs in the terminal fields
      of the dopamine neuron. The levels of PPT mRNA were significantly higher in the
      striatum, and the expression of CCK mRNA was markedly augmented in the
      hippocampus of the TN-knockout mice, compared to the wild or heterozygous mice.
      One possible explanation of the changes of PPT and CCK mRNA expressions is
      functional compensation against the low level of dopamine turnover rate in the TN
      knockout mouse brain.

PMID- 9179875
TI  - Topographic distribution and collateral projections of the two major populations
      of nigrothalamic neurons. A retrograde labeling study in the rat.
AB  - The principal target nuclei of nigrothalamic projections in the rat are the
      mediodorsal (MD) and ventromedial (VM) nuclei. The present study examined the
      patterns of distribution and collateral projections of the two major groups of
      nigrothalamic neurons, i.e., nigro-MD and nigro-VM neurons. Retrograde
      fluorescent labeling with Fluoro-Gold was used to examine whether the
      distribution areas of nigro-MD and nigro-VM neurons might be overlapped with or
      segregated from each other in the substantia nigra pars reticulata. A clear
      tendency was observed that nigro-MD neurons were distributed more ventrally than
      nigro-VM neurons. It was further examined by retrograde fluorescent double
      labeling with Fluoro-Gold and Fluoro-Ruby whether or not these nigrothalamic
      neurons might provide axon collaterals to the superior colliculus or the pontine
      reticular formation. The nigro-MD neurons were found to send axon collaterals to
      the superior colliculus more frequently than the nigro-VM neurons. Additionally,
      a small number of nigrothalamic neurons were found to send axon collaterals to
      the pontine reticular formation. The functional significance of the two major
      populations of nigrothalamic neurons was discussed on the basis of their
      collateral projections to the superior colliculus or the pontine reticular
      formation.

PMID- 9179876
TI  - Differentiation of chemically defined neuronal populations in the transplanted
      olfactory bulb without olfactory receptor innervation.
AB  - Olfactory bulbs (OBs) from embryonic day 15 and 17 and postnatal day 1 mice were
      transplanted into the lateral ventricle of juvenile host mice without bulbectomy,
      and fine structural and chemical features of neurons and glia in the OB
      transplants were investigated immunocytochemically and electron microscopically.
      In the OB transplants there were neither clearly defined glomeruli nor layers,
      nor olfactory marker protein immunoreactive elements. However, chemically defined
      neuronal populations resembling those in the normal OBs such as those
      immunoreactive for gamma-aminobutyric acid (GABA), tyrosine hydroxylase and
      Ca(2+)-binding proteins (calbindin-D28K, calretinin, parvalbumin) were observed.
      Electron microscopically, dendrodendritic and somatodendritic reciprocal
      synapses, that is, synapses characteristic of the OB, were occasionally observed
      in the OB transplants. These results indicated that at least some embryonic or
      newborn mouse OB neurons and/or precursor cells could exhibit chemical properties
      and form typical synaptic contacts observed in normal OB, even when they received
      no inputs from olfactory receptor cells.

PMID- 9179877
TI  - Strong c-Jun/AP-1 immunoreactivity is restricted to apoptotic cells following
      intracerebral ibotenic acid injection in developing rats.
AB  - Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/activator
      protein 1 (AP-1) which is raised against the amino acids 91-105 mapping with the
      amino terminal domain of mouse c-Jun p39, is observed in apoptotic cells, but not
      in necrotic cells, following intracerebral injection of ibotenic acid in the
      developing rat brain processed for immunohistochemistry. Immunostaining occurs in
      the cytoplasm and dendrites, thus suggesting impaired nuclear translocation of c
      Jun in apoptotic cells. Western blotting of total brain homogenates, using the
      same antibody, shows a band at p39 which is more marked in treated animals than
      in age-matched controls. In addition, increased c-Jun N-terminal kinase 1 (JNK-1)
      expression, as revealed on Western blots, is found in rats treated with ibotenic
      acid when compared with controls. In contrast, apoptotic cells are not stained
      with antibodies to Jun B and Jun D. These results give further support to
      previous studies showing strong c-Jun expression in apoptotic cells at
      determinate stages of development, and emphasize that intracellular distribution
      of c-Jun, possible post-translational modifications of c-Jun due to
      phosphorylation at specific transactivation sites, and lack of associated Jun B
      and Jun D expression may differentiate the Jun response in apoptotic cells from
      other forms of cellular response involving c-Jun which are not associated with
      cell death.

PMID- 9179878
TI  - Responses of adrenal function to stimulation of lumbar and thoracic interspinous
      tissues in the rat.
AB  - In urethane-anesthetized Wistar rats, the responses of adrenal sympathetic nerve
      activity and catecholamine secretion were measured following chemical stimulation
      of lumbar and thoracic interspinous tissues. Injection of normal saline into the
      lower lumbar or lower thoracic interspinous tissues produced no changes in
      adrenal sympathetic nerve activity or catecholamine secretion. On the other hand,
      the injection of capsaicin produced protracted increases in adrenal nerve
      activity and catecholamine secretion both in CNS-intact animals and in animals
      acutely spinalized at the Cl-2 level. Repetitive electrical stimulation of the
      medial branch of a lumbar primary dorsal ramus, the nerve which provides
      sensation to the lumbar interspinous tissues, produced A- and C-reflex
      discharges, mediated at the spinal and supraspinal levels, in the adrenal
      sympathetic nerve.

PMID- 9179879
TI  - Magnetoencephalographic study of intracerebral interactions caused by bilateral
      posterior tibial nerve stimulation in man.
AB  - We studied somatosensory evoked magnetic fields (SEFs) following stimulation of
      bilateral posterior tibial nerves ('bilateral' waveform) in normal subjects to
      determine the inter- and intra-hemispheric interference effects caused by
      activation of sensory areas in bilateral hemispheres. Activated areas in the
      primary and second sensory cortices (SI and SII) in each hemisphere following
      bilateral stimulation were clearly identified by estimation of the double best
      fitted equivalent current dipoles (ECD) using the spherical head model, and the
      large inter-individual differences were identified. SEFs following the right
      posterior tibial nerve stimulation and those following the left stimulation were
      summated ('summated' waveform). The 'difference' waveform was induced by a
      subtraction of 'bilateral' waveforms from the 'summated' waveform. Short-latency
      deflections showed no consistent changes between the 'summated' and 'bilateral'
      waveforms, but the long-latency deflection, the N100m-P100m, in the 'bilateral'
      waveform was significantly (P < 0.02) reduced in amplitude as compared with the
      'summated' waveform. The differences were clearly identified in the 'difference'
      waveform, in which the main deflections, U100m-D100m, were found. The ECDs of the
      short-latency deflections were located in SI contralateral to the stimulated
      nerve, but the ECDs of the N100m-P100m were located in bilateral SII which are
      considered to receive ascending signals from the body bilaterally. Therefore,
      some inhibitory interactions might take place in SII by receiving inputs from the
      body bilaterally.

PMID- 9179880
TI  - mGluR5 metabotropic glutamate receptor distribution in rat and human spinal cord:
      a developmental study.
AB  - By combining biochemical, molecular and immunohistochemical approaches, we have
      investigated the presence of metabotropic glutamate receptors (mGluRs) belonging
      to the subtype 5 in rat and human spinal cords and the developmental changes in
      their expression. A polyclonal antibody raised against the carboxy-terminal
      portion of mGluR5 was used to study the distribution of the receptor in rat
      foetal (Et15), neonatal (P8) and adult spinal cords and dorsal root ganglia
      (DRG). mGluR5 appeared to be predominantly expressed in regions containing the
      primary sensory afferents. Immunoblotting with anti-mGluR5 antibody revealed
      lower receptor protein levels in rat adult spinal cord when compared with P8 rat
      spinal cord. Reverse transcriptase-polymerase chain reaction showed both mGluR5a
      and mGluR5b mRNAs expression in rat spinal cord. The mGluR5a variant was found
      more abundant in young animals than in adults. The pattern of mGluR5
      immunostaining was also studied in foetal (6-8, 10, 12 and 22 weeks of gestation)
      and adult human spinal cord. At all stages of human development, a strong mGluR5
      immunoreactivity was observed in the dorsal roots and in the dorsal and
      dorsolateral funiculi with maximum levels of staining at week 12 of gestation.
      Foetal DRG neurons were heterogeneously labeled. mGluR5 was also diffusely
      detectable in the mantle layer. In adult human spinal cords, immunoreactivity was
      confined to laminae I and II of the dorsal horns. These results demonstrate for
      the first time the presence of mGluR5 in human spinal cord. The distribution of
      this receptor suggests a role in the development of somatosensory pathways and in
      the control of nociceptive neurotransmission.

PMID- 9179881
TI  - Response characteristics of nucleus submedius neurons to colo-rectal distension
      in the rat.
AB  - The effects of colorectal distension (CRD) were examined on neurons located in
      and around the nucleus submedius (Sm) in the medial thalamus of urethane
      anesthetized rats. A total of 66 units (49 in the Sm and 17 in immediately
      surrounding regions) responding to cutaneous pinch were tested to examine their
      responsiveness to the CRD. All the neurons that responded to cutaneous
      stimulation were nociceptive specific (NS) neurons. Based on their responses to
      the CRD the Sm neurons were classified into three types as follows: 23 (47%) of
      49 neurons in the Sm and three (18%) of 17 neurons near the Sm had tonic
      excitatory responses with long-lasting after-discharges (type I); nine (18%) Sm
      neurons and four (24%) peri-Sm neurons were tonically excited but had no after
      discharge (type II); and seven (14%) Sm neurons were inhibited (type III). Ten
      (20%) Sm neurons and 10 (59%) peri-Sm neurons did not respond to CRD. All the
      excitatory and inhibitory responses to CRD increased with increasing CRD
      pressure. Simultaneous application of CRD and cutaneous pinch did not produce a
      reduced response (nocigenic inhibition). These results demonstrate that most of
      the Sm neurons receive convergent viscerosomatic inputs from the colon and/or
      rectum and from the skin, suggesting that the Sm may participate in visceral
      nociception.

PMID- 9179882
TI  - Heterogeneity of antigen expression and lectin labeling on microglial cells in
      the olfactory bulb of adult rats.
AB  - Microglia in different layers of the rat olfactory bulb expressed a variety of
      membrane antigens except for CD4 (OX-35). Bulb microglial cells bearing
      complement receptor type 3 (OX-42) were ubiquitous and their immunoreactivity
      varied considerably in different bulb layers. Although very few in number,
      labeled microglia in all layers also expressed major histocompatibility complex
      class I antigen (OX-18), leukocyte common antigen (OX-1) and unknown macrophage
      antigen (ED-2). The latter was localized in cells distributed almost exclusively
      in the perivascular spaces. The immunoreactivity of ED-1, an unknown cytoplasmic
      or lysosomal membrane antigen in macrophages, was localized in labeled microglia
      which were concentrated mainly in the granule cell layer and periglomerular zone
      of the bulb. A variable number of microglial cells were stained with OX-6 (major
      histocompatibility complex class II antigen) and they were located predominantly
      in the periglomerular zone and at the junction between the granule cell layer and
      the subependymal layer. Ultrastructural study using GSA I-B4 lectin labeling
      showed that microglia in different layers of the bulb exhibited similar labeling
      patterns in their subcellular structures. A remarkable feature was the occurrence
      of some microglia in the olfactory nerve layer, subependymal layer and granule
      cell layer adjacent to the subependymal layer in which the cells showed intense
      lectin labeling at their Golgi apparatus, a feature which was absent in microglia
      of other bulb layers. Present results showed the regional differences in
      microglial antigen expressions and lectin labeling within the olfactory bulb. It
      is therefore suggested that the cells subserve very different specific functions
      depending on their ambient microenvironments. The heterogeneity of microglial
      functions in the olfactory bulb may be related to the progressive regeneration
      and degeneration of its containing neurons.

PMID- 9179883
TI  - Cerebellar input to corticothalamic neurons in layers V and VI in the motor
      cortex.
AB  - To investigate whether corticothalamic (CT) neurons in the motor cortex (Mx)
      receive cerebellar input via the ventroanterior-ventrolateral nucleus of the
      thalamus (VA-VL), we recorded intracellular potentials from neurons in the Mx of
      anesthetized cats and examined effects of stimulation of the VA-VL and the
      brachium conjunctivum on them. After this electrophysiological identification,
      horseradish peroxide (HRP) was injected iontophoretically into the recorded
      neurons for morphological analysis. We identified 34 neurons as CT neurons by
      their antidromic response to stimulation of the VA-VL, of which 13 were layer VI
      CT neurons and 21 were layer V CT neurons. A majority of the CT neurons of both
      layers VI and V received monosynaptic excitatory postsynaptic potentials (EPSPs)
      from the VA-VL and di- or polysynaptic EPSPs from the cerebellum. The laminar
      distribution and morphological characteristics of single CT neurons receiving
      cerebellar input were analyzed on 19 HRP-labeled CT neurons. Eight layer V and
      six layer VI CT neurons were reconstructed from serial sections. All the
      reconstructed layer VI CT neurons were modified pyramidal neurons whose apical
      dendrites ended in layer III or V, and all the stained layer V CT neurons were
      typical pyramidal neurons, although the laminar and tangential distribution of
      recurrent collaterals of these neurons varied from neuron to neuron.

PMID- 9179884
TI  - Treatment for intracranial dural arteriovenous malformations: a meta-analysis
      from the English language literature.
AB  - OBJECTIVE: The treatment of intracranial dural arteriovenous malformations
      (DAVMs) remains problematic. Options include ligature of feeding vessels,
      endovascular procedures, surgical obliteration, or a combination of the latter
      two. We conducted a meta-analysis of the English language literature on DAVMs to
      determine the most effective treatment option related to location and
      angiographic characteristics. METHODS: The criteria for inclusion were pre- and
      post-treatment angiography, a description of the type of treatment, and clinical
      outcome. The analysis included a total of 258 patients, 248 from a review of 223
      published articles and 10 from the authors' series. DAVMs were divided into six
      categories by location, and the results of treatment were compared based on
      obliteration rates using chi 2 analysis. RESULTS: In transverse-sigmoid sinus
      DAVMs (n = 64), combined therapy (endovascular plus surgical treatment) proved
      significantly more effective than either therapy alone (P < 0.01). For lesions of
      the tentorial incisura (n = 66), combined therapy and surgical obliteration alone
      proved superior to embolization (P < 0.001). For lesions of the cavernous sinus
      (n = 67), treatment was primarily endovascular, with success rates of 62 to 78%
      for transarterial and transvenous approaches, respectively. In the anterior fossa
      (n = 23), surgical obliteration was highly effective, with a success rate of 95%.
      The small number of cases in both the superior sagittal sinus (n = 28) and middle
      fossa (n = 10) regions, precluded any statistical analysis. Finally, simple
      ligature of feeding vessels produced success rates of only 0 to 8% and can no
      longer be recommended. CONCLUSION: There is no single ideal treatment for the
      obliteration of DAVMs. The management of each case is best considered
      individually. The results of this review serve as a rational starting point for
      the selection of treatment options.

PMID- 9179885
TI  - The role of transvenous embolization in the treatment of intracranial dural
      arteriovenous fistulas.
AB  - OBJECTIVE: To evaluate the role of transvenous embolization in the treatment of
      intracranial dural arteriovenous fistulas (DAVFs), including its efficacy and
      safety. METHODS: We retrospectively studied the charts of 24 patients (21 women
      and 3 men) treated for an intracranial DAVF since 1990 in whom a transvenous
      approach was attempted either alone (16 patients) or in combination with arterial
      embolization (8 patients). There were 12 cavernous sinus, 9 transverse-sigmoid
      sinus, 2 inferior petrosal sinus, and 1 intradiploic fistulas. Three fistulas
      were Type I, 12 were Type IIa, and 9 were Type IIa+b, according to the revised
      Djindjian's classification. Transvenous embolic agents included coils (17
      patients), detachable balloons (6 patients), bucrylate (2 patients), and silk
      sutures (1 patient). RESULTS: Anatomic cure was proven in 21 patients (87.5%).
      Clinical cure was obtained in 23 cases (96%), as follows: 15 patients with a
      single transvenous approach, 6 with a combined arteriovenous approach, and 2 with
      an arterial approach after failure of venous access. There was one persistent
      cavernous fistula despite coil packing of the cavernous sinus. Complications were
      as follows: five transient and one permanent sixth nerve palsies in cavernous
      DAVFs, two transient labyrinthic dysfunctions in transverse sinus DAVFs, and one
      subarachnoid hemorrhage without sequelae. CONCLUSION: Transvenous embolization is
      a useful and safe approach in the management of intracranial DAVFs.

PMID- 9179886
TI  - Ethanol endovascular management of brain arteriovenous malformations: initial
      results.
AB  - OBJECTIVE: The goal was to determine the safety and efficacy of absolute ethyl
      alcohol treatment in the management of intra-axial brain arteriovenous
      malformations (AVMs). METHODS: Seventeen patients (eight female and nine male
      patients; mean age, 41 yr) underwent ethanol endovascular therapy for treatment
      of their brain AVMs. Superselective amytal testing preceded all procedures.
      Neuroleptic intravenous anesthesia was used for 16 patients, and general
      anesthesia was used for 1 patient. Follow-up monitoring consisted of clinical
      evaluations, magnetic resonance imaging, and arteriography. RESULTS: In follow-up
      evaluations (mean follow-up period, 13 mo) after embolization of brain AVMs,
      neither vascular recanalization nor the neovascular recruitment phenomenon was
      observed in any patient. Progressive AVM thrombosis at arteriographic follow-up
      evaluation was a constant feature. Seven patients were cured of their AVMs with
      ethanol endovascular therapy alone. Three patients were cured of their lesions
      with ethanol embolization plus surgical resection. One patient was cured of his
      lesion with ethanol embolization and radiation therapy of the residual nidus.
      Three patients underwent only partial therapy, with significant improvement in
      symptoms. Three patients are currently undergoing ethanol endovascular therapy.
      Complications occurred with 8 of 17 patients, most of which were transient. Two
      patients died because of late subarachnoid hemorrhages, one patient 4 months and
      one patient 14 months after partial therapy. CONCLUSION: Progressive and
      permanent AVM occlusion is a common finding in arteriographic follow-up
      evaluations. In no patients did arterial recanalization or the neovascular
      recruitment phenomenon occur. Our initial results indicate that ethanol has a
      permanence that is seldom encountered with other embolic agents. With aggressive
      decadron therapy, the complications related to swelling in the brain are largely
      reversible.

PMID- 9179887
TI  - Long-term follow-up study of unruptured intracranial aneurysms.
AB  - OBJECTIVE: The purpose of this study was to clarify the risk of rupture of
      unruptured intracranial aneurysms among large groups of patients with various
      underlying diseases or conditions. METHODS: A long-term follow-up study of
      unruptured intracranial aneurysms was performed with 360 patients who were
      treated conservatively during the period from April 1969 to December 1992.
      RESULTS: Follow-up evaluation (between February and June 1994) could be performed
      for 234 (65%) of the patients. The underlying diseases included multiple
      aneurysms with subarachnoid hemorrhage for 60 patients, cerebral infarction for
      108, intracerebral hemorrhage for 27, and other diseases for 39. Single aneurysms
      were present in 171 patients and multiple aneurysms in 63. The mean follow-up
      period was 75 months (range, 3-270 mo). Of the 234 patients, 132 (56.4%)
      survived, 59 (25.2%) died because of other diseases, 9 (3.8%) underwent surgery,
      and 34 (14.5%) showed bleeding from unruptured aneurysms, which was fatal for 18
      of the patients. The average annual rupture rate for all patients was 2.3%
      (subarachnoid hemorrhage, 3.2%; cerebral infarction, 2.2%; intracerebral
      hemorrhage, 3.2%; other diseases, 3.6%). There were no significant differences
      among the patients according to underlying disease or aneurysm site. The
      cumulative rate of bleeding for all patients was 20% at 10 years after diagnosis
      and 35% at 15 years. The cumulative probability of rupture was significantly
      higher for the multiple aneurysms than the single aneurysms (P < 0.001).
      CONCLUSION: The risk of rupture of unruptured aneurysms is high, especially for
      multiple aneurysms, but there are no significant differences in the risk of
      rupture according to the underlying disease or the aneurysm location. Radical
      treatment should be considered for patients with unruptured intracranial
      aneurysms.

PMID- 9179888
TI  - Cerebral blood flow and autoregulation in normal pressure hydrocephalus.
AB  - OBJECTIVE: We tried to identify indications for cerebrospinal fluid shunting in
      patients with normal pressure hydrocephalus. METHODS: We studied the cerebral
      blood flow (CBF) and vascular response to acetazolamide in the white matter,
      cortex, and thalamus of 21 patients with normal pressure hydrocephalus, comparing
      patients who improved clinically after shunting with those who did not. We used
      xenon-enhanced computed tomography for the CBF measurements. RESULTS:
      Preoperatively, both groups had globally reduced CBF, but the reduction was more
      pronounced in the unimproved patients. The vascular response was impaired only in
      the white matter of the patients who improved later. After shunting, restoration
      of CBF, more marked in the white matter, and recovery of vascular response in the
      white matter paralleled clinical improvement and a reduction in ventricular
      dilation and periventricular lucency on computed tomographic scans in nine
      patients. The CBF reduction, however, deteriorated in the 12 patients who did not
      improve clinically. CONCLUSION: We conclude that the underlying disease in the
      improved patients was ischemia, with a loss of autoregulatory capacity in the
      periventricular white matter caused by cerebrospinal fluid diffusion. Those who
      did not improve had irreversible brain damage in which the CBF reduction was
      secondary to metabolic depression and autoregulation was preserved. We also
      conclude that patients suspected of having normal pressure hydrocephalus will
      improve clinically after shunting if preoperative hemispheric CBF is greater than
      20 ml/100 g per minute and the vascular response to acetazolamide is impaired
      only in the periventricular white matter. They will not improve, however, if the
      preoperative CBF is less than 20 ml/100 g per minute and the vascular response to
      acetazolamide is intact.

PMID- 9179889
TI  - One-year outcome after decompressive surgery for massive nondominant hemispheric
      infarction.
AB  - OBJECTIVE: Massive cerebral infarction is often accompanied by early death
      secondary to transtentorial herniation. We have tested the hypothesis that
      decompressive hemicraniectomy for massive nondominant cerebral infarction is
      lifesaving in a series of 14 patients presenting with right hemispheric
      infarction and clinical signs of uncal herniation and impending death. We have
      further analyzed, in prospective follow-up examinations, the levels of physical,
      psychiatric, and social disabilities in these patients. METHODS: The methods used
      included retrospective analysis to determine rates of immediate mortality and
      morbidity after surgical intervention. Prospective follow-up data were obtained
      to determine the level of recovery in surviving patients after 1 year.
      Standardized measures of outcome to assess physical, psychiatric, and social
      recovery included the Barthel Index, Zung Depression Scale, and Reintegration to
      Normal Living Index. RESULTS: With decompressive hemicraniectomy, we were able to
      prevent death secondary to transtentorial herniation in all cases; 11 patients
      experienced long-term survival after the procedure, and three deaths were related
      to non-neurological causes. We observed that 8 of the 11 surviving patients were
      at home, were functioning with minimal to moderate assistance, and had Barthel
      scores greater than 60. The remaining three patients were severely disabled.
      Seven of the 11 survivors were able to walk at 1 year after undergoing the
      procedure. Depression and failure to reintegrate socially were experienced by
      most patients. CONCLUSION: This series confirms the lifesaving nature of
      hemicraniectomy in patients deteriorating because of cerebral edema after
      infarction. In patients younger than 50 years, recovery to a state of near
      independence is possible.

PMID- 9179890
TI  - The significance of carotid canal involvement in basilar cranial fracture.
AB  - OBJECTIVE: Basilar cranial fractures have been associated with injury to the
      carotid artery. We sought to determine whether fracture through the carotid canal
      was a significant risk factor for carotid injury. METHODS: A retrospective chart
      review was performed, and 230 patients with basilar cranial fractures were
      identified. Fifty-five of the 230 patients had visible fractures that extended
      through one or both carotid canals (CC fx group). Evidence for vascular injury,
      based on medical records, angiography, magnetic resonance imaging, and other
      studies, was compiled. The anatomic characteristics of the fractures were also
      noted and recorded. RESULTS: Ten patients in the CC fx group suffered vascular
      complications; for six of them, the complications were directly related to the
      intracranial carotid artery. This compares to four patients in the non-CC fx
      group with vascular complications (P < 0.005), only one of which was carotid
      specific (P < 0.005). The most common site of fracture through the canal was at
      the junction of the lacerum and cavernous portions of the canal (the spheno
      occipital suture) (62% of all carotid canal fractures occurred at that site);
      however, vascular injury was seen most often in patients who sustained fractures
      through the petrous segment (67% of carotid canal-specific injuries occurred in
      that group, and 25% of patients with petrous canal fractures suffered carotid
      injury, [P = not significant]). The mean Glasgow Coma Scale score and the mean
      age were both lower (P < 0.05) in the CC fx group. CONCLUSION: Vascular
      complications are more frequently observed after basilar cranial fractures when
      there is involvement of the carotid canal. The lacerum-cavernous junction, which
      is partly formed by the spheno-occipital suture, is the most frequently fractured
      segment of the carotid canal. Fracture through the petrous segment of the carotid
      canal is associated with a relatively high incidence of carotid injury. Fracture
      through the carotid canal may serve as an index of injury severity, because
      patients with these fractures suffered more severe head injuries.

PMID- 9179891
TI  - Epidemiology of brachial plexus injuries in a multitrauma population.
AB  - OBJECTIVE: The purpose was to identify the prevalence, causative factors, injury
      types, and associated injury patterns in multitrauma patients who sustained
      brachial plexus injuries. METHODS: A retrospective review of a prospectively
      collected and computerized database and a chart review were performed. RESULTS:
      Brachial plexus injuries were identified in 54 of 4538 (1.2%) patients presenting
      to a regional trauma facility. Young male patients predominated. Motor vehicle
      accidents were the most frequent cause overall, but only 0.67% of such accidents
      resulted in plexus injuries. Conversely, 4.2% of motorcycle accident victims and
      4.8% of snowmobile accident victims suffered brachial plexus injuries. Injuries
      were supraclavicular for 62% of patients and infraclavicular for 38%.
      Supraclavicular injuries were more likely to be severe (Sunderland Grade 3 or 4),
      compared with infraclavicular injuries, which were neurapraxic in 50% of cases (P
      < 0.01). The former therefore required surgical exploration and reconstruction
      more often (52 versus 17%; P < 0.05). Associated injuries included closed head
      injuries with loss of consciousness in 72% of patients (coma in 19%), cervical
      spine fractures in 13%, and clavicle, scapular, or humeral fractures and shoulder
      dislocations or sprains in 15 to 22%. Rib fractures were observed in 41% and were
      complicated by internal thoracic injuries in a similar percentage of cases. The
      injury severity score ranged from 5 to 59, with a mean of 24, and two patients
      died. CONCLUSION: Brachial plexus injuries afflict slightly more than 1% of
      multitrauma victims. Motorcycle and snowmobile accidents carry especially high
      risks, with the incidence of injury approaching 5%. Head injuries, thoracic
      injuries, and fractures and dislocations affecting the shoulder girdle and
      cervical spine are particularly common associated injuries. Supraclavicular
      injuries are more common, are of more severe grade, more often require surgery,
      and are associated with worse prognosis, compared with infraclavicular injuries.

PMID- 9179892
TI  - Management and outcomes of posterior fossa subdural hematomas in neonates.
AB  - OBJECTIVE: To review and analyze a contemporary series of 15 neonates who were
      treated for posterior fossa subdural hematomas (PFSDHs) during the era of
      computed tomography and magnetic resonance imaging. METHODS: A retrospective
      chart review identified all neonates with PFSDHs for whom neurosurgical
      consultations were obtained for treatment planning. RESULTS: There were nine male
      and six female patients. The mean gestational age was 39 weeks. Nine of the 15
      mothers of the patients were primiparous. Instrument-assisted delivery (forceps
      and/or vacuum extractor) was undertaken for seven patients. The mean birth weight
      of the infants was 3165 g (range, 2160-3930 g). The mean 5-minute Apgar score was
      7.5. Symptoms of PFSDH developed within the first 24 hours of life in 13
      neonates. The predominant symptoms and signs were failure to thrive,
      irritability, seizures, apnea, and bradycardia. Lumbar punctures to rule out
      central nervous system sepsis were performed in six neonates. Hemograms revealed
      that six neonates were anemic with low hemoglobins, five had low platelets, and
      four had abnormal prothrombin and/or partial thromboplastin times at the time of
      diagnosis. Computed tomography established the diagnosis of PFSDH in all cases.
      Magnetic resonance imaging was performed for two neonates. The median time to
      diagnosis by imaging studies was 10 hours after birth. Surgical evacuation of the
      PFSDHs was performed in eight neonates. Seven neonates were followed
      conservatively with serial imaging studies. There was no mortality in either
      treatment group. Follow-up ranged from 2 to 10 years, with a mean of 4.5 years.
      Functional outcome assessment revealed that seven neonates were
      neurodevelopmentally normal, three were mildly delayed, two were moderately
      delayed, and three were profoundly delayed. In addition to traumatic causes of
      the PFSDHs, three neonates were observed to have coagulation disturbances at
      birth and one was observed at follow-up to have a posterior fossa medulloblastoma
      that had bled at birth. CONCLUSION: PFSDHs are rare but important lesions to
      diagnose early in the neonatal period. Surgery can be life-saving when performed
      in a timely manner for signs and symptoms of brain stem dysfunction. A search for
      an underlying cause predisposing to a PFSDH may, on occasion, reveal a
      coagulation disturbance or a neoplasm that will require additional therapeutic
      considerations.

PMID- 9179893
TI  - Use of cortical surface vessel registration for image-guided neurosurgery.
AB  - OBJECTIVE: We have treated patients with brain surface tumors by using video
      registration of a three-dimensional image to the surgical field, to identify
      eloquent cortices, localize the lesions, and define the tumor margins. "Skin-to
      skin" registration using the skin surface to produce alignment was performed
      earlier but was difficult in areas with few prominent registration landmarks. For
      this reason, "vessel-to-vessel" registration using the cortical vessels as
      fiducials was applied to 17 cases, to improve accuracy. This article presents the
      advantages and limitations of vessel-to-vessel registration, as determined from
      the data for these cases. The accuracy is also estimated. METHODS: A three
      dimensional model was reconstructed from magnetic resonance imaging data, and a
      two-dimensional projection was superimposed on the video image of the actual
      surgical field. The tumor was resected with guidance from the registered video
      image. The two-dimensional projection accuracy of vessel-to-vessel registration
      was compared with that of skin-to-skin registration by using a phantom study.
      RESULTS: All 17 tumors underwent gross total resection, and the patients
      experienced no major permanent neurological deficits. In the phantom study, the
      two-dimensional, projected, target registration error of a tumor with skin-to
      skin registration was estimated as 8.9 +/- 5.3 mm and that with vessel-to-vessel
      registration was 1.3 +/- 1.4 mm (99th percentile confidence intervals, 24.8 and
      5.5 mm, respectively). CONCLUSION: Video registration using cortical surface
      vessels is practical and improves two-dimensional projection accuracy
      significantly, compared with skin registration.

PMID- 9179894
TI  - Microsurgical anatomy and clinical significance of the anterior communicating
      artery and its perforating branches.
AB  - OBJECTIVE: Precise identification of the anomalous anterior communicating artery
      (ACoA) or the perforating branches of the ACoA is usually difficult on
      preoperative angiograms because of the vascular complexity around the ACoA and
      its small-caliber branches. The purpose of this study was to review the
      microsurgical anatomy of the ACoA and its branches to show their importance for
      the interhemispheric trans-lamina terminalis approach and ACoA aneurysmal
      surgery. METHODS: In 30 cadaver brains, the ACoA and its branches were examined
      under magnification using a surgical microscope. RESULTS: The ACoA was evident in
      all specimens and had variations consisting of plexiform (33%), dimple (33%),
      fenestration (21%), duplication (18%), string (18%), fusion (12%), median artery
      of the corpus callosum (6%), and azygous anterior cerebral artery (3%). The
      perforating branches were also observed in all cadaver brains. They were
      classified into subcallosal, hypothalamic, and chiasmatic branches according to
      their vascular territories. The subcallosal branch, usually single and the
      largest, supplied the bilateral subcallosal areas, branching off to the
      hypothalamic area. The hypothalamic branches, multiple and of small caliber,
      terminated in the hypothalamic area. CONCLUSION: The incidence of anomalous ACoA
      was higher than has been previously reported, and any segment of the anomalous
      ACoA may have perforating branches regardless of diameter. Among the three
      branches, the subcallosal branch is the most important because it feeds bilateral
      subcallosal areas branching to the hypothalamic area.

PMID- 9179895
TI  - Microvascular surgical anatomy of the vertebrobasilar junction.
AB  - OBJECTIVE: We examined the pertinent microvascular anatomy of 28 formalin-fixed
      brains to develop anatomic guidelines for aneurysm surgery in the region of the
      vertebrobasilar junction. METHODS: Using a surgical microscope, the outer
      diameters were observed for the following main arteries: vertebral, basilar,
      posteroinferior cerebellar, and anteroinferior cerebellar. The number of lower
      brain stem perforating arteries was examined in relation to their course. The
      distance between the arteries and their perforators was measured with respect to
      anatomic landmarks. RESULTS: The anatomy of the main arteries was
      characteristically variable, whereas the anatomy of the perforators was constant,
      particularly in terms of their numbers and points of penetration into the brain
      substance. The four major points of entry were the lateral medullary area just
      caudal to the posterior olivary sulcus, the posterior olivary sulcus, the small
      lateral fossa at the superior olivary groove, and the foramen cecum. Each of
      these areas coincides with the origin of common vertebrobasilar aneurysms.
      CONCLUSION: The anatomy of the main arteries was variable. In contrast, the
      perforators penetrated the adjoining brain stem at specific locations, regardless
      of the caliber of the main artery. Despite a small vertebral artery or its major
      branches, perforators penetrating the brain are significant and may effect the
      outcome of aneurysm surgery or endovascular procedures.

PMID- 9179896
TI  - Is there a superior occipitofrontal fasciculus? A microsurgical anatomic study.
AB  - OBJECTIVE: Using a fiber-dissection technique, our aim was to expose and study
      the myelinated fiber bundles of the brain to achieve a clearer conception of
      their configurations and locations. During the course of our study, the superior
      occipitofrontal fasciculus became the focus of our interest. Many publications
      have defined this as a bundle of association fibers, located between the corpus
      callosum and the caudate nucleus, that connects the frontal and occipital lobes.
      By examining this area using fiber dissection, we realized that the descriptions
      of the anatomy are inadequate; thus, we focused on the elucidation of the
      anatomic structures of this region and, in particular, that known as the superior
      occipitofrontal fasciculus. METHODS: Twenty previously frozen, formalin-fixed
      human brains were dissected under the operating microscope using the fiber
      dissection technique. RESULTS: On coronal sections of the brain, a structure on
      the superolateral aspect of the caudate nucleus usually has been identified as
      the superior occipitofrontal fasciculus. However, our fiber dissections revealed
      that this structure is the superior thalamic peduncle, that it is composed of
      projection fibers rather than association fibers, and that it does not
      interconnect the occipital and frontal lobes. CONCLUSION: The structures of the
      brain are better understood when the fiber-dissection technique is used to
      explore their configurations and locations. The resulting information is
      especially beneficial for planning strategies and tactics of neurosurgical
      procedures.

PMID- 9179897
TI  - Ion implantation and protein coating of detachable coils for endovascular
      treatment of cerebral aneurysms: concepts and preliminary results in swine
      models.
AB  - OBJECTIVE: Complete anatomic obliteration remains difficult to achieve with
      endovascular treatment of wide-necked aneurysms using Guglielmi detachable
      platinum coils (GDCs). Ion implantation is a physicochemical surface modification
      process resulting from the impingement of a high-energy ion beam. Ion
      implantation and protein coating were used to alter the surface properties
      (thrombogenicity, endothelial cellular migration, and adhesion) of GDCs. These
      modified coils were compared with standard GDCs in the treatment of experimental
      swine aneurysms. METHODS: In an initial study, straight platinum coils were used
      to compare the acute thrombogenicity of standard and modified coils. Modified
      coils were coated with albumin, fibronectin, or collagen and underwent Ne+ ion
      implantation at a dose of 1 x 10(15) ions/cm2 and an energy of 150 keV. Coils
      were placed in common iliac arteries of 17 swine for 1 hour, to evaluate their
      acute interactions with circulating blood. In a second study, GDCs were used to
      treat 34 aneurysms in an additional 17 swine. GDCs were coated with fibronectin,
      albumin, collagen, laminin, fibrinogen, or vitronectin and then implanted with
      ions as described above. Bilateral experimental swine aneurysms were embolized
      with standard GDCs on one side and with ion-implanted, protein-coated GDCs on the
      other side. The necks of aneurysms were evaluated macroscopically at autopsy, by
      using post-treatment Day 14 specimens. The dimensions of the orifice and the
      white fibrous membrane that covered the orifice were measured as the fibrous
      membrane to orifice proportion. Histopathological evaluation of the neck region
      was performed by light microscopy and scanning electron microscopy. RESULTS:
      Fibronectin-coated, ion-implanted coils showed the greatest acute thrombogenicity
      (average thrombus weight for standard coils, 1.9 +/- 1.5 mg; weight for
      fibronectin-coated coils, 8.6 +/- 6.2 mg; P < 0.0001). By using scanning electron
      microscopy, an intensive blood cellular response was observed on ion-implanted
      coil surfaces, whereas this was rare with standard coils. At Day 14, greater
      fibrous coverage of the necks of aneurysms was observed in the ion-implanted coil
      group (mean fibrous membrane to orifice proportion of 69.8 +/- 6.2% for the ion
      implanted coil group, compared with 46.8 +/- 15.9% for the standard coil group; P
      = 0.0143). CONCLUSION: The results of this preliminary experimental study
      indicate that ion implantation combined with protein coating of GDCs improved
      cellular adhesion and proliferation. Future application of this technology may
      provide early wound healing at the necks of embolized, wide-necked, cerebral
      aneurysms.

PMID- 9179898
TI  - Rapid reversal of endothelin-1-induced cerebral vasoconstriction by intrathecal
      administration of nitric oxide donors.
AB  - OBJECTIVE: To determine the capability of donors of nitric oxide (NO) (sodium
      nitroprusside, nitroglycerine) to reverse endothelin-1 (ET-1)-induced cerebral
      vasoconstriction in vivo, when administered through the cerebrospinal fluid (CSF)
      to the adventitial side of the constricted blood vessel. METHODS: The rabbit
      basilar artery was exposed through a transcervical, transclival approach and
      subsequently subjected to pharmacological manipulations and direct observation of
      effects by videomicroscopy. Specific manipulations were suffusion of ET-1 (100
      nmol/L, 1 ml/min) in synthetic CSF (sCSF) to provoke vasoconstriction and then
      either suffusion of an NO donor in sCSF (2 mg/ml/min), or sCSF alone. The second
      suffusion was always made separately and begun during the period of stable
      maximal vasoconstriction, which occurred between 20 and 30 minutes after
      beginning the first suffusion. Measurements of the diameter of the artery were
      made using an inline video caliper. RESULTS: Sodium nitroprusside and
      nitroglycerine, both donors of NO, rapidly and completely reversed ET-1-induced
      vasoconstriction without causing hypotension. The average value for maximal
      vasoconstriction by ET-1/sCSF was 50.4% of baseline arterial diameter and
      occurred between 20 and 30 minutes. The rate of vasodilatory response was 100% of
      significantly constricted arteries. The response was complete in less than 6
      minutes in all preparations, as compared to the 60 minutes required for
      spontaneous relaxation (sCSF suffusion alone). CONCLUSION: NO donors are
      effective in reversing cerebral vasoconstriction when administered intrathecally,
      cause no significant hemodynamic change when so administered, and may represent
      an important therapeutic intervention for cerebral vasospasm.

PMID- 9179899
TI  - Growth-inhibitory and differentiation-inducing activity of dimethylformamide in
      cultured human malignant glioma cells.
AB  - OBJECTIVE: To determine the growth-inhibitory and differentiation-inducing
      activity of dimethylformamide (DMF) on a human glioma cell line (SHG-44). DMF is
      a type of polar solvent and a potent differentiation-inducing agent in many kinds
      of human solid tumors, yet its effect on human glioma remains unclear. METHODS:
      The effects of DMF on cell proliferation using 3-(4,5-dimethyl thiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assay, cell cycle distribution (with flow
      cytometry), colony-forming efficiency in double-layer soft agar, tumorigenicity
      in athymic nude mice, morphological changes, and glial fibrillary acidic protein
      expression were studied. RESULTS: At dose ranges of 0.25, 0.5, 0.75, and 1.0%,
      DMF caused a dose-dependent proliferation inhibitory effect in monolayers and a
      marked dose-dependent suppression of colony-forming efficiency in double-layer
      soft agar with a complete loss of colony-forming ability in cells exposed to 0.75
      and 1.0% DMF. Accumulation of cells in G0/G1 phases was observed in DMF-treated
      (0.5 and 1.0%) cells, also in a dose-dependent manner. SHG-44 cells exposed to
      DMF (0.5 and 1.0%) for 15 days changed morphologically from small spindle-shaped
      to large polygonal and flattened stellate cells with multiple slender processes.
      These cells were still tumorigenic in athymic nude mice, but the growth of
      xenografts was remarkably reduced, especially in the 1.0% DMF-treated group. The
      expression of glial fibrillary acidic protein was notably increased by DMF (0.5
      and 1.0%). Washout experiments revealed that the effects of DMF on cell
      proliferation and cell cycle distribution were reversible. CONCLUSION: Our
      results suggest that DMF drove the SHG-44 cells to a more mature phenotype with
      inhibited growth.

PMID- 9179900
TI  - Evaluation of lipid-coated microbubbles as a delivery vehicle for Taxol in brain
      tumor therapy.
AB  - OBJECTIVE: This work evaluates the potential of lipid-coated microbubbles (LCM)
      as a delivery vehicle for lipid-soluble antineoplastic agents. We have shown, in
      rats, the selective affinity of intravenously administered LCM for tumor cells.
      They are internalized by the tumor cells both in vitro and in vivo. The
      specificity of LCM for tumors and subsequent incorporation into the cytoplasm
      could significantly reduce the systemic effects of an agent incorporated into the
      bubbles, such as Taxol. METHODS: The in vitro methods were as follows. C6 cells
      (10(5) cells) were treated with Taxol-LCM (6 micrograms/ml), Taxol-Cremophore (6
      micrograms/ml), or LCM alone for 8 or 24 hours. Cell death was determined by
      staining the cells with nuclear staining. Abnormalities of microtubule structures
      were ascertained by confocal microscopy. The in vivo methods were as follows. Two
      rat tumor models (C6 and 9L) were used. Rats were treated with single bolus
      injections or with repetitive (two or three) treatment courses, with respective
      control animals. Each course consisted of one daily tail vein injection for 5
      consecutive days and then 2 days of rest. RESULTS: When compared with either a
      saline control group or a group receiving Taxol in an oil vehicle, Taxol-LCM
      reduced tumor progression in Fischer 344 rats inoculated with 9L glioma. The most
      profound effect was observed with rats treated with three treatment cycles (five
      daily injections/cycle) separated by two rest periods (2 d/period). CONCLUSION:
      Both in vitro and in vivo data indicate that Taxol can be incorporated into LCM,
      can be delivered to the tumor site, and can exert a measurable antitumor
      biological effect.

PMID- 9179901
TI  - Brain edema in meningiomas is associated with increased vascular endothelial
      growth factor expression.
AB  - OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor
      (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of
      endothelial cells and increases vascular permeability dramatically. All gliomas
      secrete significant amounts of VEGF, whereas meningiomas are variable in
      expression. Thus, we sought to determine whether the extent of VPF/VEGF
      expression in meningiomas correlated with differences in brain edema associated
      with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men,
      average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent
      surgery at or were referred to the University of Alabama Hospital were examined
      retrospectively for the extent of expression of immunoreactive VPF/VEGF.
      Additionally, peritumoral edema was assessed on a blinded basis radiographically
      from preoperative magnetic resonance imaging scans. Selected specimens were
      examined by in situ hybridization to document the source of VPF/VEGF. RESULTS:
      The predominant meningioma subclassifications were transitional (57%) or
      meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5,
      with a median value of 2 on a subjective 5-point scale; magnetic resonance
      imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale),
      with a median value of 2.5. The correlation of determination (R2) of magnetic
      resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity
      rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized
      VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal
      parenchymal brain cells. CONCLUSION: These data suggest that meningioma
      associated edema may be a result of the capacity of meningioma cells to produce
      VPF/VEGF locally, leading to increased tumor neovascularization and enhanced
      vascular permeability.

PMID- 9179902
TI  - Choroid plexus papilloma in the posterior third ventricle: case report.
AB  - OBJECTIVE AND IMPORTANCE: The case of a 42-year-old woman with a choroid plexus
      papilloma (CPP) arising from the posterior wall of the third ventricle is
      described. This case is very unusual because the tumor did not have any
      connection with the choroid plexus but was attached to the normal brain
      parenchyma. CLINICAL PRESENTATION: The patient presented with the symptoms of
      increasing intracranial pressure. Magnetic resonance imaging revealed
      hydrocephalus related to a small mass in the posterior third ventricle, occluding
      the aqueduct. INTERVENTION: Surgery confirmed that the tumor was located at the
      surface of the posterior commissure without having any connection to the normal
      choroid plexus. A histopathological examination revealed a CPP with no attachment
      to the choroidal tissue. CONCLUSION: A review of the literature demonstrates that
      CPPs without any connection to the choroid plexus are very unusual. To our
      knowledge, this is the first reported case of such a CPP that developed on the
      posterior wall of the third ventricle in which no choroid plexus was present.
      Furthermore, this tumor, to our knowledge, is also the smallest intraventricular
      CPP to be verified at surgery.

PMID- 9179903
TI  - Granulocytic sarcoma of the spine in nonleukemic patients: report of three cases.
AB  - OBJECTIVE AND IMPORTANCE: Granulocytic sarcomas involving the spine in patients
      without myelogenous leukemia are rare. We report three cases and review the
      literature. CLINICAL PRESENTATION: Three patients presented with spinal epidural
      tumors, which caused spinal cord compression in one and cauda equina compression
      in two. INTERVENTION: All patients underwent surgery, and biopsies revealed
      histological features of granulocytic sarcomas. Bone marrow aspirates and
      biopsies showed no evidence of acute leukemia at initial presentation, for all
      three patients. CONCLUSION: Granulocytic sarcomas in nonleukemic patients are
      rare, and when they affect the spine they are frequently misdiagnosed.
      Appropriate therapy for these tumors requires early identification.

PMID- 9179904
TI  - Retropharyngeal pseudomeningocele after atlanto-occipital dislocation: report of
      two cases.
AB  - OBJECTIVE AND IMPORTANCE: We report two cases of retropharyngeal
      pseudomeningocele after atlanto-occipital dislocation. This is rare, with only
      one other reported case in the literature. CLINICAL PRESENTATION: We report two
      patients who presented after blunt cervical and head trauma. Plain films revealed
      that each patient had atlanto-occipital dislocation. Subsequent magnetic
      resonance imaging revealed the delayed development of retropharyngeal
      pseudomeningocele. Concomitant hydrocephalus was noted in both patients.
      INTERVENTION: The surviving patient showed marked neurological improvement and
      resolution of his pseudomeningocele after ventriculoperitoneal shunting.
      CONCLUSION: For patients with closed head injuries who develop posttraumatic
      pseudomeningocele, we recommend cranial computed tomography to assess for the
      presence of hydrocephalus. In patients with atlanto-occipital dislocation,
      delayed neurological deterioration warrants magnetic resonance imaging of the
      craniocervical junction to rule out posttraumatic pseudomeningocele.

PMID- 9179905
TI  - Unusual foreign body causing quadriparesis: case report.
AB  - OBJECTIVE AND IMPORTANCE: An unusual foreign body traversing the spinal canal at
      the foramen magnum level is described. Interesting radiological findings and a
      review of nonmissile penetrating injuries are presented. This case demonstrates
      the importance of a thorough physical examination and the use of neurodiagnostic
      imaging in an inebriated, uncooperative patient with neurological dysfunction.
      CLINICAL PRESENTATION: The patient presented with quadriparesis confounded by
      cocaine intoxication. A physical examination revealed only a small punctate
      lesion in the posterior occipital region. INTERVENTION: After detection of the
      foreign body, the patient underwent immediate surgical exploration and removal of
      the object. The dura was repaired primarily, and the patient was maintained on
      intravenous antibiotics for 7 days. CONCLUSION: With physical therapy, the
      patient was walking with assistance at 2 weeks postsurgery. Upper extremity
      strength, especially intrinsic hand movement, was most severely affected. At 10
      months' follow-up, the patient's only deficits were mild intrinsic hand weakness
      and incoordination with fine finger movements. Immediate surgical exploration is
      indicated for patients with retained fragments and progressive neurological
      dysfunction.

PMID- 9179906
TI  - Unusual intramedullary vascular lesion: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Spinal arteriovenous malformations have been divided by
      location into dural (Type I), intramedullary glomus (Type II), juvenile (Type
      III), and perimedullary direct arteriovenous fistulae (Type IV). We report two
      cases of an unusual intramedullary proliferation of hyalinized capillaries that
      do not fit into any of these categories. CLINICAL PRESENTATION: A 27-year-old
      woman and a 62-year-old man presented with subacute progressive caudal
      myelopathy. Magnetic resonance imaging revealed focal spinal cord enlargement,
      high signal on T2-weighted images, and patchy enhancement with gadolinium
      consistent with tumor. No serpentine flow voids were visualized on the surface of
      the spinal cord. Spinal angiography revealed nothing abnormal. No abnormal
      vasculature was grossly visible on open biopsy. Histological examination of the
      tissue specimens revealed a proliferation of capillary-sized vessels with varying
      degrees of vascular wall changes ranging from endothelial hyperplasia to
      concentric hyalinization, suggesting ongoing evolution of the lesion. Surrounding
      neural tissue demonstrated ischemic changes characterized by myelin and axonal
      loss and astrocytosis but no necrosis. INTERVENTION: Patients were treated with
      chronic anticoagulation, which seemed to slow, but not halt, symptomatic disease
      progression. CONCLUSION: Although the pathological substrate seems to be an
      acquired intramedullary vascular lesion characterized primarily by capillary
      proliferation, the cause of this lesion is unknown. This disease differs from
      Foix-Alajouanine syndrome and subacute necrotizing myelopathy by an absence of
      abnormal surface vessels and a lack of intramedullary necrosis. The histological
      findings are reminiscent of the process that occurs in the kidney and various end
      organs from long-standing mild to moderate elevations in blood pressure or
      chronic diabetes. Tissue ischemia may result from luminal obstruction by severe
      hyalinization and thrombosis. Because the natural history of this disease is
      unknown, it is unclear whether anticoagulation slowed disease progression.

PMID- 9179907
TI  - Interlocking-clipping technique for giant aneurysms of the internal carotid
      artery: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Direct clipping of giant intracranial aneurysms is
      sometimes difficult. A unique technique using multiple fenestrated clips for
      closing a giant aneurysm is described. CLINICAL PRESENTATION: A 65-year-old woman
      presented with a 10-month history of headache and gait disturbance. Cerebral
      angiography disclosed an unruptured giant aneurysm of the right internal carotid
      artery. INTERVENTION: Surgical exposure confirmed the presence of a giant
      aneurysm with the splaying and incorporation of the parent artery and a number of
      perforating arteries originating from the dome. Four angled and three straight
      fenestrated clips were applied in tandem to the aneurysm to reconstruct the
      parent artery and preserve the perforating vessels. Through their blades and
      heads, the closely arranged clips were successfully interlocked. CONCLUSION: This
      "interlocking-clipping" technique is a modification of the tandem clipping
      technique. The aim of this approach is to enhance closing pressure and allow a
      more stable "seating" of the clips in giant cerebral aneurysms.

PMID- 9179908
TI  - Transmaxillary approach to the anterior cavernous sinus: a microanatomic study.
AB  - OBJECTIVE: Several approaches to expose the anterior cavernous sinus have been
      used, such as frontotemporal, orbitofrontal, anterior subtemporal, and various
      transfacial approaches. In an effort to gain exposure to the anterior cavernous
      sinus without necessitating a craniotomy or wide transfacial exposure, the
      authors in the present study have developed a transmaxillary approach to the
      cavernous sinus. METHODS: The approach was developed using data obtained by
      performing 24 cadaveric dissections. Using a sublabial incision to expose the
      maxilla, maxillotomy is performed and the course of the infraorbital nerve is
      identified as a guide to the maxillary branch of the trigeminal nerve. After an
      osteotomy of the posterior sinus wall and pterygoid plate, the foramen rotundum
      is identified, which lies a mean of 10 mm from the posterior wall of the maxilla.
      A superomedial enlargement of the foramen rotundum is then undertaken to
      ultimately expose the anterior cavernous sinus. RESULTS: This technique offers
      access to all cavernous cranial nerves, as well as the entire course of the
      anterior loop of the internal carotid artery to the origin of the ophthalmic
      artery. With a mean operative range of 38 mm from the posterior wall of the
      maxilla to the anterior loop of the internal carotid artery, this approach offers
      adequate exposure with a short operative distance. CONCLUSION: The approach may
      be useful in limited exposure of tumors of the anterior cavernous sinus and some
      intracavernous vascular lesions.

PMID- 9179909
TI  - Repair of an arterial perforation of the internal carotid artery using Hemashield
      wrapping with aneurysm clip reinforcement: technical note.
AB  - OBJECTIVE: To review a technique used to repair a hole in the carotid artery
      encountered during the dissection and clipping of a giant paraclinoid aneurysm.
      METHODS: The technique of repair involves wrapping the artery using a woven
      double velour material impregnated with bovine collagen (Hemashield; Meadox,
      Oakland, NJ) and securing the material around the carotid artery with an aneurysm
      clip. The intravascular pressure of the carotid artery provides the counterforce
      necessary to seal the hole. RESULTS: The carotid artery was slightly narrowed
      after the treatment. The patient made an excellent recovery from surgery.
      CONCLUSION: This technique provides an alternative means of repairing a defect in
      the walls of intracranial arteries.

PMID- 9179910
TI  - Charles A. Elsberg (1871-1948).

PMID- 9179912
TI  - Technetium-MIBI as a glioma imaging agent for the assessment of multi-drug
      resistance.
AB  - OBJECTIVE: To explore the presence of MDR-1 drug resistance in human glioma
      utilizing a Single Photon Emission Computerized Tomography (SPECT) imaging agent,
      sesta-MIBI, and testing cases interpreted as positive for drug resistance with
      molecular characterization of subsequent tissue biopsy, including RNA, Northern
      blot analysis, and polymerase chain reaction, and in situ hybridization. METHODS:
      Six patients that carried a diagnosis of biopsy-proven glioma underwent dual
      isotope SPECT imaging with thallium 201 and technetium sesta-MIBI. All six
      patients underwent subsequent surgical reexcision of their tumors, and tissue was
      immediately flash frozen for further analysis. PolyA RNA was isolated and
      subsequently analyzed by both Northern blot analysis and RT-PCR utilizing an MDR
      1 probe (ATCC) and MDR-1 primers. RESULTS: Four patients with SPECT concordance
      yielded tumors without MDR-1 expression whereas two patients with SPECT
      discordance yielded tumors with MDR-1 gene expression. In one discordant case we
      subsequently performed RT-PCR in situ amplification/ hybridisation and
      immunohistochemistry with, respectively, an MDR-1 sense primer with Biotin
      labeled probes and an MDR-1 monoclonal antibody, and both analyses revealed MDR-1
      expression in tumor cells. CONCLUSION: These data support the use of SPECT
      technetium sesta-MIBI to evaluate the presence of MDR-1 gene expression in
      gliomas.

PMID- 9179913
TI  - A pitfall in the surgery of a recurrent aneurysm after coil embolization and its
      histological observation: technical case report.

PMID- 9179914
TI  - Prognostic value of psychological testing in patients undergoing spinal cord
      stimulation: a prospective study.

PMID- 9179915
TI  - Secretion of chorionic gonadotropin from human trophoblasts.

PMID- 9179916
TI  - The effect of monophosphoryl lipid A on lipopolysaccharide-induced prostaglandin
      E2 release in human choriodecidua.
AB  - The aim of this study was to determine the effect of an inhibitor of bacterial
      endotoxin, monophosphoryl lipid A (MLA), on lipopolysaccharide (LPS)-induced
      prostaglandin E2 (PGE2) formation by human choriodecidua explants incubated in
      vitro. LPS induced the release of PGE2 from explants in a time-and dose-dependent
      manner (P < 0.05, n = 5), thus establishing the efficacy of the experimental
      model. MLA at concentrations of 10 micrograms/ml also increased PGE2 release from
      explants when compared to vehicle controls (P < 0.05, n = 5). When used at a
      concentration that did not stimulate PGE2 release (1 microgram/ml), MLA
      pretreatment, coincubation or a combination of these protocols did not
      significantly affect LPS-induced PGE2 release. These data establish that MLA does
      not act by abrogating tissue LPS responsiveness. Under the conditions utilized in
      this study, MLA acts locally as a low potency 'LPS-like agent'. The previously
      reported in vivo efficacy of systemically administered MLA may involve the
      partial depletion or down regulation of LPS response pathways and the subsequent
      development of LPS tolerance.

PMID- 9179917
TI  - Immunohistochemical localization of lipoperoxidation products in normal human
      placenta.
AB  - 4-Hydroxynonenal (4-HNE) is a major propagation product of lipid peroxidation
      that is supposed to be responsible for some of the effects associated with
      oxidative stress in tissues. We have investigated the possible occurrence and
      distribution of 4-HNE-immunoreactivity in human normal placenta using
      immunocytochemistry. Specific immunostaining was observed in cytotrophoblast
      cells, syncytiotrophoblast, some cells of the villous mesenchyme and some
      endothelial cells of first trimester and term placentae. The detection of 4-HNE
      immunoreactivity in placenta raises the question whether lipoperoxidation
      products are produced locally in placental cells or represent exogenous products
      that derive from maternal blood flow. Since trophoblastic cells and villous
      macrophages are provided by a scavenger receptor, it is conceivable that these
      cells may play a protective role with regard to the diffusion of lipoperoxidation
      products from the mother to the embryo. However, since a significant degree of
      lipid oxidative modification does not take place in plasma, it is presumed that 4
      HNE is a local product of placental metabolism. In line with this hypothesis, it
      is proposed that maternal low density lipoproteins, which are the major source of
      cholesterol for placental steroid synthesis, might be oxidized by villous cells
      during their traversal through the villous wall.

PMID- 9179918
TI  - Decrease in cytochrome c oxidase activity detected cytochemically in the
      placental trophoblast of patients with pre-eclampsia.
AB  - This study was designed to explore the possible relationship between
      cytochemically detectable cytochrome c oxidase (COX) activity in the trophoblast
      and placental dysfunction in patients with pre-eclampsia. Fifteen placentae (10
      from women with an uncomplicated pregnancy and five from patients with pre
      eclampsia) were involved in this study. Localization of COX activity in the
      placental trophoblast was determined by ultrastructural enzyme cytochemistry
      using DAB as a capturing agent. COX activity was observed in the intracristal
      spaces and intermembrane spaces of trophoblastic mitochondria. The number of
      mitochondria positive for COX staining was decreased markedly in the placentae of
      the women with pre-eclampsia. Trophoblastic mitochondrial dysfunction may be
      present in placenta of patients with pre-eclampsia.

PMID- 9179919
TI  - Inducible (type II) nitric oxide synthase in human placental villous tissue of
      normotensive, pre-eclamptic and intrauterine growth-restricted pregnancies.
AB  - We have utilized two distinct monospecific antibodies against the type II
      (macrophage or inducible) nitric oxide synthase (NOS) isoform to localize the
      distribution of the enzyme within the human placenta in tissues from normotensive
      pregnancies and those complicated by pre-eclampsia and/or intrauterine growth
      restriction. Both antibodies immunolocalize to cells in the villous stroma on
      frozen sections of villous tissue. Colocalization studies with anti-CD14 or anti
      CD45 antibodies that recognize cells of leucocyte or monocyte/macrophage lineage
      indicate that Hofbauer cells are expressing type II NOS. This is in contrast to
      expression of type III (endothelial) NOS which is seen in syncytiotrophoblast and
      in villous vascular endothelium. In some, but not all, normotensive and
      pathologic placental tissue, some type II NOS immunostaining could be seen in
      syncytiotrophoblast and vascular endothelium; however, no differences could be
      discerned between groups of tissues. Expression of type II NOS by Hofbauer cells
      may indicate they are involved in surveillance against maternal immune insult or
      maternal pathogens whereby they secrete nitric oxide to exert a
      cytostatic/cytotoxic effect.

PMID- 9179920
TI  - Placental expression of vascular endothelial growth factor in placentae from
      pregnancies complicated by pre-eclampsia and intrauterine growth restriction does
      not support placental hypoxia at delivery.
AB  - In view of the pathological placental features of pre-eclampsia and intrauterine
      growth restriction (IUGR), and the angiogenic effects of vascular endothelial
      growth factor (VEGF), the aim of this study was to determine the expression of
      VEGF in placentae from normal pregnancies and to compare the results with
      placentae from pregnancies complicated by pre-eclampsia and intrauterine growth
      restriction (IUGR). ELISA was used to measure circulating VEGF immunoreactivity
      in umbilical vein serum samples and immunohistochemistry was used to determine
      tissue expression of the protein. Since VEGF is known to be upregulated by
      hypoxia, the expression pattern of VEGF would provide further clues to the oxygen
      status in the placentae at the time of sampling, presently a subject under great
      debate. The geometric mean concentration of VEGF immunoreactivity in umbilical
      vein serum of normal pregnant women was 112.46 pg/ml, in women with pre-eclampsia
      50.23 pg/ml and in IUGR alone 175.35 pg/ml. These values were not statistically
      different from each other. Immunolocalization of VEGF in normal term villous
      placenta was observed in the syncytiotrophoblast with less intense staining in
      stromal cells. No qualitative differences in localization of staining between the
      groups (normal pregnancies, pre-eclampsia, pre-eclampsia plus IUGR, and IUGR) was
      found. Intensity of staining in stromal cells was also similar in the groups
      studied. However, intensity of VEGF immunostaining in syncytiotrophoblast was
      significantly reduced in the three pathological groups (P < 0.02) compared with
      the control group. These results suggest that reduced VEGF may be responsible, at
      least in part, for the impaired vascular development which occurs in these
      conditions. Our results are therefore not consistent with villous placental
      hypoxia at the time of sample collection.

PMID- 9179921
TI  - Expression of stromelysin-3 in the human placenta and placental bed.
AB  - Human placentation is mediated by fetal trophoblastic cells which penetrate into
      the decidualized uterine endometrium. Trophoblast invasion requires the precisely
      regulated secretion of specific proteinases able to degrade the endometrial
      basement membranes and extracellular matrix. To document further the involvement
      of these proteinases during human placentation, we evaluated in vivo the
      expression of stromelysin-3, a member of the metalloproteinase family, during the
      first and third trimesters of pregnancy, by means of immunohistochemistry, in
      situ hybridization and Northern blot analysis. Human extravillous trophoblasts
      invading the maternal decidua produced stromelysin-3 during both, the first and
      third trimesters of pregnancy, but to a lesser extent during the latter. In
      floating villi, stromelysin-3 expression was restricted to the
      syncytiotrophoblasts that line intervillous vascular spaces. In conclusion,
      stromelysin-3 is expressed by differentiated, non-proliferative villous and
      extravillous trophoblastic cells in early and late placental beds and villi, and
      its pattern of expression evolves during pregnancy. Our observations suggest that
      stromelysin-3 could play a role in human placentation.

PMID- 9179922
TI  - Determination of intervillous flow in early pregnancy.
AB  - The process of placentation in the macaque has been extensively studied and found
      to resemble closely that observed in the human. In this model,
      histopathologically, intervillous flow is anticipated from week 3 post
      conception. We set out to document the nature and onset of intervillous flow in
      the macaque in vivo using colour Doppler imaging (CDI), colour Doppler energy
      (CDE) and pulsed-wave Doppler (PWD). Pregnant females were assessed between 15-50
      days gestation (term = 165 days) with an Acuson 128/XP10 high-resolution
      ultrasound scanner, using a 7-MHz linear array probe. The placenta, subjacent
      decidua and myometrium were assessed using CDI and CDE. Specific regions of flow
      were interrogated using PWD; the resulting flow velocity waveforms were stored
      and quantified using conventional Doppler indices. B-mode sonography was able to
      demonstrate the well-defined placental-decidual interface observed in this
      species; CDI and CDE clearly visualized the uteroplacental vasculature. Spiral
      arteries were followed to their point of discharge into the intervillous space,
      and PWD at these sites obtained a characteristic flow velocity waveform. The
      indices obtained confirmed a flow of low resistance and pulsatility throughout
      the gestation studied. Flow within the intervillous space was noted from day 20
      of gestation.

PMID- 9179923
TI  - Variations in expression of copper/zinc superoxide dismutase in villous
      trophoblast of the human placenta with gestational age.
AB  - This study investigated expression of the key antioxidant enzyme copper/zinc
      superoxide dismutase in the villous trophoblast of the human placenta at
      different gestational ages from 8 weeks (last menstrual period) to term.
      Immunostaining for the enzyme was observed in the cytotrophoblast cells at all
      stages. Staining was generally absent from the syncytiotrophoblast at 8 weeks,
      except for small isolated areas close to the basal surface. The size and location
      of these areas suggested they were the result of recent cytotrophoblastic fusion.
      By 10 weeks, examples were more frequent and diffuse staining throughout most of
      the syncytiotrophoblast was observed at 12 weeks. The intensity of the
      immunostaining within the syncytiotrophoblast continued to increase until 14
      weeks, by which time it matched generally that within the cytotrophoblast cells.
      A similar pattern of staining was observed within term material. These results
      are entirely consistent with the hypothesis that the oxygen tension within the
      intervillous space is low throughout the first trimester of pregnancy. They
      support the idea that an effective maternal circulation to the human placenta is
      only established at the start of the second trimester.

PMID- 9179924
TI  - Detection of elastin in the human fetal membranes: proposed molecular basis for
      elasticity.
AB  - The human fetal membranes provide a sterile biomechanical container which adjust
      by growth to mid-pregnancy to the increase in fetal size, and by elasticity to
      the forceful movements of the fetus. The molecular basis for this elasticity is
      not known, yet reduced elasticity may lead to their premature rupture and preterm
      birth, a major problem in perinatal medicine. Classically, elastin confers the
      property of elastic recoil to elastic fibres which are assembled from a family of
      tropoelastin precursors. These are covalently cross-linked to form insoluble
      elastin by formation of desmosine and isodesmosine, catalysed by the enzyme lysyl
      oxidase. The amnion, chorion and decidua were shown by Northern analysis and RT
      PCR to contain detectable levels of tropoelastin mRNA and the mRNA encoding lysyl
      oxidase. The proteins encoded by these mRNAs were also identified by Western
      blotting and immunolocalization. Further, insoluble elastin was extracted from
      the human fetal membranes and shown by comparison to elastin preparations from
      other elastic tissues to have a reasonable desmosine content. Finally, scanning
      electron microscopy confirmed the presence of multiple layers of an apparently
      very thin elastic system in this tissue. This biochemical and histopathologic
      study has demonstrated therefore that the human fetal membranes synthesize and
      deposit a novel elastic fibre. The presence of such an elastic system in these
      tissues provides, for the first time, a probable molecular basis for the elastic
      properties of this tissue.

PMID- 9179925
TI  - Angiotensin mediated interaction of fetal kidney and placenta in the control of
      fetal arterial pressure and its role in hydrops fetalis.
AB  - Fetal cardiovascular control is effected by an interaction of the fetal somatic
      and placental circulations. Three primary regulatory mechanisms are involved:
      transplacental transfer of extracellular fluid, driven by a difference in
      hydrostatic and oncotic pressures; modulation of fetal placental and somatic
      vascular resistances by means of blood pressure controlled production of
      angiotensin; and somatic autoregulation of flow. A systems analysis incorporates
      these and other fetal cardiovascular functions and this analysis was modelled for
      computer simulation. Given physiologically plausible values for known
      cardiovascular parameters in the fetal sheep, the model reproduced in detail a
      variety of experimental protocols with known outcomes; these included the normal
      fetus, the fetus after bilateral nephrectomy, the nephrectomized fetus infused
      with angiotensin, the intact fetus infused with NaCl solutions, the fetus with
      lymphatic obstruction and the severely anaemic fetus. The systems analysis
      demonstrated that fetal cardiac failure constituted the strongest stimulus for
      the formation of fetal oedema of any tested pathological intervention.

PMID- 9179926
TI  - Hypoxanthine uptake at the fetal side of human placenta proceeds through a
      nucleobase-preferring carrier and a non-saturable process.
AB  - Uptake and metabolism of hypoxanthine by human placenta were studied using the
      single-circulation paired-tracer technique. In isolated cotyledons perfused
      through the fetal (basal) circulation, at mean pressures of 31.7 +/- 4.0 mmHg and
      mean flow rates maintained at 5.5 +/- 0.15 ml/min, the [3H]hypoxanthine uptake
      was 36 +/- 2.4 per cent (16.5 +/- 1.1 pmol/g wet weight). Hypoxanthine uptake was
      significantly inhibited by unlabelled (mM) hypoxanthine (0.5), adenine (0.5),
      guanine (0.5) and papaverine (15.0), but was unaffected by nitrobenzylthioinosine
      (0.01). Adenosine failed to inhibit hypoxanthine uptake. The kinetic analysis of
      hypoxanthine uptake showed it to be partially mediated by a saturable (apparent
      K(m) = 12.1 +/- 1.85 microns; Jmax = 7.1 +/- 0.52 nmol/min) and Na(+)-dependent
      mechanism. A greater fraction of hypoxanthine influx proceeded through a non
      saturable process. Thin layer chromatographic analysis of venous perfusate after
      the intra-arterial injection of [3H]hypoxanthine showed a negligible degradation
      of nucleobase. These overall results show that hypoxanthine uptake at the fetal
      side of human placenta occurs by a saturable plus a non-saturable process. The
      carrier showed specificity for nucleobases and high affinity-low capacity for
      hypoxanthine. Since the fetal blood concentration of hypoxanthine is normally
      low, its uptake would be mediated by the high affinity transport system. Because
      the non-saturable mechanism can be operative at high concentrations of
      hypoxanthine, it may have primary importance to clear the nucleobase coming from
      the fetus during intrauterine hypoxia.

PMID- 9179927
TI  - Expression of the facilitated glucose transporters (GLUT1 and GLUT3) by a
      choriocarcinoma cell line (JAr) and cytotrophoblast cells in culture.
AB  - The expression of GLUT1 and GLUT3 mRNA and protein in human placental trophoblast
      derived cells was investigated. A dividing choriocarcinoma derived cell line
      (JAr) was compared to differentiating cytotrophoblast cells, isolated from human
      term placenta, following 18 (mononucleate) and 66 h (multinucleate) in culture.
      JAr cells treated with 8-bromoadenosine, which inhibits growth and induces
      differentiation, were also studied. GLUT1 mRNA and protein expression were
      similar in the four groups of cells. However, GLUT3 mRNA expression was
      significantly higher (six- to sevenfold) in both control and 8-bromoadenosine
      treated JAr cells compared to cytotrophoblast cells and was also significantly
      higher in untreated versus treated JAr cells. Western blotting showed that GLUT3
      protein was undetectable in either cytotrophoblast cell groups, but was abundant
      in both groups of JAr cells. GLUT3 protein in JAr cells treated with 8
      bromoadenosine was also significantly lower than in untreated JAr cells, in
      agreement with the mRNA data. We conclude that GLUT1 expression is unaffected by
      either growth or differentiation of trophoblast cells whereas GLUT3 expression is
      associated with dividing cells. We propose that in the placenta, GLUT3 may be
      involved in maintaining metabolic requirements of dividing trophoblast cells,
      rather than having a direct role in transport of glucose to the fetus.

PMID- 9179928
TI  - Effects of cadmium on trophoblast calcium transport.
AB  - Maternal exposure to cadmium (Cd) during pregnancy has been linked to low fetal
      birthweight, which may be attributed to placental damage and/or dysfunction in
      nutrient transport. Previous studies have suggested that Cd is accumulated in the
      placenta, and that placental transport of calcium (Ca) and zinc (Zn) is perturbed
      by Cd. To investigate the mechanism of Cd perturbation of Ca transport, we used
      JEG-3, a human choriocarcinoma cell line which exhibits trophoblastic properties,
      to analyse Cd effects in vitro. Treatment with Cd at low, physiologically
      relevant concentrations (e.g. 0.04 microM) did not result in obvious changes in
      cell morphology or integrity, whereas higher concentrations (> or = 0.16 microM)
      affected cell integrity. With lower concentrations of Cd treatment for 24 h,
      activities of cellular Ca uptake and transport, and Ca2+ binding were decreased,
      and intracellular [Ca2+] ([Ca2+]i) profile was also altered; however, membrane
      associated Ca(2+)-activated ATPase activity remained relatively unchanged.
      Interestingly, cellular Ca uptake activity was unaffected by short-term (30 min)
      Cd pretreatment. The 24-h Cd treatment also resulted in elevated expression of
      the metal-binding protein, metallothionein, whereas the expression of a
      trophoblast-specific cytosolic Ca(2+)-binding protein (HCaBP) was drastically
      reduced. These results strongly suggest that Cd exposure significantly
      compromises the Ca handling ability of trophoblastic cells; this effect is
      probably not due to perturbations in Ca channel or membrane Ca pump activities,
      but rather a consequence of alterations in subcellular, cytosolic Ca2+ binding
      activities.

PMID- 9179929
TI  - Aspects of calcium transport by the ovine placenta: studies based on the
      interplacentomal region of the chorion.
AB  - An in vitro technique for the measurement of calcium uptake into the maternal
      facing fetal chorionic membrane (apical trophoblast) was used to study the
      relationship between calcium uptake and stage of pregnancy in the sheep. The
      effects on calcium uptake of varying calcium concentration and temperature of the
      incubation medium, of adding calcium channel blockers or heavy metals (lanthanum
      and nickel) or calcium ionophore/agonist were also studied. The data indicate a
      saturable calcium uptake process, plateauing after 15 min incubation. This uptake
      remained constant throughout the last third of gestation until a significant fall
      in uptake was noted during the final week prior to parturition. This uptake was
      not due to extracellular cellular diffusion since there was no significant uptake
      of tritiated inulin over the same period in each case. Calcium uptake in this
      system was also shown to be a temperature dependent process which was abolished
      at temperatures of 0-4 degrees C. A decrease in calcium concentration to 0.12 mM
      in the incubation medium also caused a corresponding decrease in calcium uptake
      to 21 per cent of control (1.2 mM). The addition of the heavy metals lanthanum
      and nickel also significantly reduced calcium uptake as did the calcium channel
      blockers verapamil, metoprolol and diltiazem. The calcium channel ionophore
      A23187 increased calcium uptake into the material facing chorion. Although the
      interplacentomal chorion may not be representative of the whole of the placental
      unit, it clearly contains a specific calcium uptake process under local
      physiological control. The blocking of calcium uptake by the specific I-type
      calcium channel blocker verapamil may indicate the presence of I-type channels of
      unusually low sensitivity since the concentration needed to block them was much
      higher than would be required for excitable I-type channels in isolated cells.

PMID- 9179930
TI  - Immunocytochemical identification of the oestrogen receptor in the nuclei of
      cultured human placental syncytiotrophoblasts.
AB  - We have shown that oestrogen has a central integrative role in regulating key
      components of the progesterone biosynthetic and corticosteroid metabolic pathways
      within syncytiotrophoblasts that govern placental function and maturation of the
      fetal pituitary-adrenocortical axis. Studies utilizing classic binding procedures
      and RNAse protection have demonstrated that human placental villous tissue
      exhibits specific high affinity oestrogen binding and expresses the mRNA for the
      oestrogen receptor. However, it is not known whether the oestrogen receptor is
      expressed specifically in syncytiotrophoblasts. Therefore, the present study
      determined whether the oestrogen receptor protein was detectable by
      immunocytochemistry in cultured human syncytiotrophoblast maintained in a low
      oestrogen/progestin environment. Cytotrophoblasts were isolated from human term
      placentae by trypsin dispersion and Percoll gradient centrifugation and cultured
      for 5, 7 or 10 days. Incubation of syncytiotrophoblast with 5-10 micrograms/ml of
      the anti-oestrogen receptor rat monoclonal antibody D-75, which is specific for
      the primate oestrogen receptor, resulted in identification of the oestrogen
      receptor in the nuclei of these cells. In contrast, there was no reactivity of
      the trophoblasts to either rat IgG or an irrelevant rat monoclonal antibody IgG2a
      against mouse common leukocyte antigen T200. Collectively, these findings
      indicate that oestrogen receptor is expressed in the nuclei of human placental
      syncytiotrophoblasts and support the suggestion that the syncytiotrophoblast is
      an oestrogen-responsive tissue.

PMID- 9179931
TI  - William Turner's lectures on the comparative anatomy of the placenta.

PMID- 9179932
TI  - Solute translocation across placental membranes.

PMID- 9179933
TI  - CSF-1 autocrine loop in an immortalized human trophoblast cell-line.

PMID- 9179934
TI  - Historical perspectives in epileptic psychosis in Japan.
AB  - It was as long ago as 1908 when the first study of epileptic psychosis appeared
      from Japan. Major literatures since that time with regard to psychoses in
      patients with epilepsy in Japan are reviewed. The history of epileptic psychoses
      could be divided into five eras according to the main interests in that period:
      (i) dawn of the history of epileptic psychoses; (ii) the early era; (iii) the era
      of periodic psychoses; (iv) the middle era; and (v) the present era. The main
      topics in each era are described and re-evaluated herein.

PMID- 9179935
TI  - Changing pattern of mental health utilization in Hachijojima.
AB  - We have reviewed retrospectively 229 patients interviewed by the mental health
      team in the Hachijojima since the establishment of our services in 1987. The 6
      year observation period was classified into three chronological stages for the
      purposes of identifying any change in the utilization pattern of the mental
      health services of the island. The rate of schizophrenia was observed to have
      decreased from 48% in the first 2 years of the study period to 28% in the last 2
      years; while that of other mental disorders increased yearly. Interestingly, an
      increasing number of patients were referred to our services by professionals in
      areas other than mental health (from 42 to 77%), and patients without any history
      of psychiatric treatment were more frequently seen (from 36 to 75%) in the later
      part of the study period. These changes suggest the importance of access to
      mental health services.

PMID- 9179936
TI  - Genetic and clinical correlates of season of birth of schizophrenics.
AB  - The genetic and clinical characteristics of 55 patients with schizophrenia and
      138 control patients (with major psychiatric disorders), were studied in relation
      to the season of birth. The morbid risk (MR) of schizophrenia was significantly
      higher among relatives of the schizophrenic probands born in Spring than among
      those of the psychiatric controls born in the same season. The MR of
      schizophrenia was also significantly higher among relatives of schizophrenic
      probands born in Winter or Spring (6.9%) than in those of schizophrenic probands
      born in Summer or Autumn (0%). Among the schizophrenic cases, Winter births were
      marginally related to the paranoid subtype, whereas other clinical variables
      showed no clear relationship with the season of birth.

PMID- 9179937
TI  - Validity and reliability of the Japanese version of the Stress and Coping
      Inventory.
AB  - We examined the validity and reliability of the Japanese version of the Stress
      and Coping Inventory (SCI) among 170 Japanese college students and 234 healthy
      subjects. The validity and reliability of this version of the SCI in the college
      student group were supported by significant test-retest correlations, relatively
      high internal consistency coefficients, and adequate correlations with the Coping
      Inventory for Stressful Situations (CISS). AS for the healthy subject group, the
      reliability was supported by relatively high internal consistency coefficients,
      although further analyses, such as test-retest, are required. The Japanese
      version of the SCI appears to be suitable for use among college students.

PMID- 9179938
TI  - Clinical features of childhood-onset schizophrenia with obsessive-compulsive
      symptoms during the prodromal phase.
AB  - Thirty-nine patients with schizophrenia, diagnosed according to DSM-III-R, who
      were under 15 years of age, were studied in two groups; 16 subjects with
      obsessive-compulsive symptoms during the prodromal phase, and 23 with no
      obsessive-compulsive disorders. The group with obsessive-compulsive symptoms
      during the prodromal phase was characterized by a higher ratio of males, higher
      incidences of perinatal and brain computed tomography (CT) abnormalities, fewer
      hereditary factors, longer duration of the prodromal phase, and a higher
      incidence of insidious onset and negative symptoms compared with the group
      without such prodromal symptoms. Schizophrenic patients with obsessive-compulsive
      symptoms during the prodromal phase were clinically distinct from those without,
      which suggests the possibility of subtype categorization.

PMID- 9179939
TI  - The effect of coping on the caregiver of elderly patients with dementia.
AB  - Ninety-eight caregivers of elderly patients with cognitive impairment were
      surveyed by questionnaires in order to examine the relationship between their
      coping strategies and subjective burden. Confrontative coping and avoidance
      coping were significantly associated with their burden. The severity of cognitive
      impairment and the behavioral problems of the patients were also significantly
      associated with the caregivers' burden. However, a multiple regression analysis
      suggested that the caregivers' coping strategies may be more important than the
      patients' condition in terms of the effects on the burden.

PMID- 9179940
TI  - Improvement in excessive daytime sleepiness after surgical treatment for
      obstructive sleep apnea syndrome.
AB  - The author's goal was to investigate the effects of surgical treatment on
      psychophysiological measurements in 17 patients with obstructive sleep apnea
      syndrome (OSAS) and also to clarify the improvement process of each evaluation.
      Given the changes in respiratory disturbance and sleep architecture, it was
      obvious that surgical treatment had therapeutic effects on OSAS patients a few
      months after the surgery. In that process, a dissociation between objective and
      subjective sleepiness was observed. The improvement in objective sleepiness
      [multiple sleep latency test (MSLT)] was more delayed than the improvement in
      subjective sleepiness (Stanford Sleepiness Scale, Spaceaeromedicine fatigue
      checklist). The improvement of MSLT was associated with an improvement in sleep
      fragmentation. This finding suggests that the disruption of sleep continuity
      accompanied by respiratory disturbance might be responsible for the occurrence of
      objective sleepiness. It can be concluded that the effective management of OSAS
      needs to address the full range of psychophysiological manifestations, especially
      objective measurement of daytime sleepiness.

PMID- 9179941
TI  - Transient P300 abnormality of event-related potentials following unilateral
      temporal lobectomy.
AB  - Event-related potentials (ERP) were recorded during auditory oddball tasks for a
      patient prior to and soon after left anterior temporal lobectomy. The N100
      amplitude decreased bilaterally although the latency did not change after the
      lobectomy. The P300 amplitude decreased in the left hemisphere at 1 and 2 weeks
      after surgery, then recovered to the pre-operative level at 4 weeks. These
      findings suggest that the medial temporal structure participates in the
      generating system of P300.

PMID- 9179942
TI  - Effect of antiepileptic drugs on thyroid function.
AB  - Chronic treatment with antiepileptic drugs (AED) is known to reduce serum thyroid
      hormone levels. Serum thyrotropin (TSH) level is unchanged despite low thyroxine
      (T4) level. We studied serum tri-iodothyronine (T3), T4 and TSH in 30 epileptic
      patients prior to discontinuation and 2, 4, 8 and 16 weeks after AED
      discontinuation. One AED was discontinued in each patient. Serum T3 levels were
      reduced consistently after AED discontinuation. Serum T4 and rT3 levels were
      increased, but not persistently. Serum TSH levels were unchanged. Our results
      suggest that during AED treatment serum T3 level was increased. This could be an
      increased conversion of T4 to T3. An acceleration of thyroid hormones degradation
      by enzyme induction is physiologically balanced by an increased conversion of T4
      to T3.

PMID- 9179943
TI  - Effects of antidepressants on thyroid stimulating hormone release in rats under
      ether stress.
AB  - We found inhibitory effects of antidepressants (clomipramine, maprotyline,
      mianserin and zimelidine) and 5-hydroxytryptophan (5-HTP) on thyroid stimulating
      hormone (TSH) release induced by ether stress in freely moving rats. We confirmed
      that ether stress suppressed the plasma TSH levels after 30 min. We then injected
      intravenously 250 ng thyrotropin releasing hormone (TRH), 0.1 mg/kg clomipramine,
      2.5 mg/kg maprotyline, 2.5 mg/kg mianserin, 0.5 mg/kg zimelidine and 25 mg/kg 5
      HTP simultaneously. These materials blocked the influences on plasma TSH levels
      by the ether stress. Serotonergic antidepressants (clomipramine, zimelidine) and
      5-HTP (precursor of serotonin) had a higher potency against the ether stress.
      These results suggest that antagonizing effects against the ether stress may
      involve the serotonergic system in the pituitary gland.

PMID- 9179944
TI  - Effectiveness of nilvadipine in two cases of chronic schizophrenia.
AB  - Nilvadipine is a calcium channel inhibitor used commonly for the treatment of
      cerebrovascular insufficiency. We observed two patients with schizophrenia whose
      psychiatric symptoms and tardive dyskinesia improved after the addition of
      nilvadipine to their antipsychotic drug regimen. The total score of the brief
      psychiatric rating scale (BPRS) in case 1 fell from 56 to 42 after 8 weeks on
      nilvadipine; while that of case 2 fell from 44 to 32. The total score of the
      abnormal involuntary movement scale (AIMS) in case 2 decreased from 12 to 7. No
      adverse effects occurred during treatment. Nilvadipine may thus offer a new
      approach to the adjunctive treatment of schizophrenia.

PMID- 9179945
TI  - Life and death from a psychiatric perspective. Introduction.

PMID- 9179946
TI  - A Japanese perspective on crisis intervention.
AB  - This paper describes the author's therapeutic team's general rules for crisis
      intervention that have been built up by gaining experience in therapy and crisis
      intervention for 'difficult cases to treat'. It discusses how the author's
      therapeutic team actually intervenes in the crisis, building a relationship as
      quickly as possible with the patient and/or family, and providing follow-up
      treatment with the family and others involved in the crisis. The paper then
      outlines recent trends in Japanese crisis intervention in comparison with the
      Western system of psychiatric emergency services. Finally, the paper concludes
      the necessity of establishing comprehensive and on-going community-care in order
      for a psychiatric emergency system to become successful in Japan.

PMID- 9179947
TI  - Clinical evaluation of suicide risk.
AB  - Suicide risk assessment may well be the most complex clinical task that mental
      health professionals face. Tests have shown to be of little use. To confront this
      complexity, assessment and prediction are best seen as interwoven with
      understanding suicide, a multi-dimensional malaise. With the essential concepts
      of lethality and perturbation, a clinical theory of suicide is presented.
      Intrapsychic aspects (i.e., unbearable psychological pain, cognitive
      constriction, indirect expressions, inability to adjust, and ego) as well as
      interpersonal aspects (i.e., interpersonal relations, rejection-aggression,
      identification-egression), are outlined to aid in assessment. Transference and
      countertransference issues in assessment are noted. A case illustration to aid in
      clinical insight is provided. It is concluded that all assessment and prediction
      of suicide risk ultimately depends on the skill of the clinician.

PMID- 9179948
TI  - Suicide in adolescence and crisis intervention in Japan.

PMID- 9179949
TI  - Prevention of late life suicide: when, where, why and how.
AB  - Suicide in late life is discussed from the perspective of four guidelines derived
      from preventive medicine; preventive efforts (1) are beneficial in proportion
      both to the prevalence and severity of a disease, (2) must consider how the
      outcome might affect individuals and society as a whole, (3) should take into
      account biological, psychological and social dimensions, (4) can only be
      effective if important and 'alterable' risk factors are identified. Possible risk
      factors for late life suicide which may be altered include social isolation,
      stressful circumstances, and affective disorder. Primary prevention may involve
      outreach programs to decrease social isolation, secondary prevention may include
      education of primary care physicians, and tertiary prevention may, in patients
      with severe affective disorder, include hospitalization and aggressive somatic
      therapies.

PMID- 9179950
TI  - Suicide risk in the general hospital.
AB  - This paper reviews the relationship between physical illness and suicide, reviews
      the studies of attempters and completers of suicide in general hospitals, and
      discusses those studies which have investigated the characteristics of patients
      in the medical setting with suicidal ideation. Study of suicidal ideation in a
      general hospital setting aimed at characterizing patients' suicidality may allow
      psychiatrists to better discriminate those patients at greater risk for completed
      suicide. Comparison of medical patients with suicidal ideation with those who had
      attempted or completed suicide, and recommendations to reduce suicidal impulses
      and treat these patients are discussed.

PMID- 9179951
TI  - Suicide and mental disorders.
AB  - In Japan, there has not yet been a complete psychological autopsy study. The
      author conducted a retrospective study of failed suicides (quasi-completed
      suicides) admitted to an emergency critical care center. According to the
      lethality of suicide methods, 133 out of 265 subjects over 6 years (1986-1991)
      were classified as the absolutely dangerous (AD; the failed suicides) group. As a
      principal diagnosis, psychoses, endogenous depression, substance abuse were
      present in 75% of the AD group. The diagnostic distribution largely differed with
      depressive disorders being mainly in the older group (50+ years), and psychoses
      predominating in the younger group (< 30 years). This study suggested that the
      majority of suicide victims in Japan also had mental disorders, and suicide
      prevention should be confronted with this clinical fact.

PMID- 9179952
TI  - Attempted suicide: efficacy of treatment programs.
AB  - Persons with a history of attempted suicide have an increased risk of eventually
      committing suicide. Eleven controlled perspective studies are reviewed on
      treatment programs aimed at reducing the rates of suicide and of repeated
      suicidal attempt in these considered at risk. None of these aftercare programs
      had a demonstrable impact on the suicide rate, and only in one investigation was
      a significant reduction of repeated attempts observed. Lack of statistical power
      and inadequate treatment strategies are discussed as major contributors to this
      failure. Recent evidence of a reduction of suicide rates and mortality by
      consequent and long-term treatment of patients with affective disorders, as well
      as reports of undertreatment of depression prior to completed suicide, might
      provide a new stimulus for the development and evaluation of aftercare programs
      for those who attempt suicide. The available evidence advocates a shift of
      emphasis from crisis management to the identification and treatment of
      psychiatric illness in this risk group.

PMID- 9179953
TI  - Recent trends in suicidal behavior in Japan.
AB  - This paper reviews the present situation of suicidal behavior in Japan. Although
      the suicide rate among the younger generation has been decreasing steadily, that
      among elderly Japanese has been high. In addition, it is expected that the
      elderly population in Japan will increase more rapidly than in other countries in
      the 21st century. This paper highlights the problems of suicidal elderly in
      Japan, by focusing on characteristics of their psychopathology, and it proposes
      an integrated model for suicide prevention. Accurate knowledge about suicide
      crisis in the elderly and appropriate countermeasures should be acquired by every
      individual in the community, and efficient social support networks should be
      established. The long-term objective should be to create an environment in which
      senior citizens can contribute to the community to the best of their ability, and
      every effort should be made to decrease the social stigma against old age and
      suicide.

PMID- 9179954
TI  - Mental disorders and suicide prevention.
AB  - In the research phase of the National Suicide Prevention Project, all suicides (n
      = 1397) in Finland between March 1987 and April 1988 were examined
      retrospectively using the psychological autopsy method. Careful retrospective
      diagnostic evaluation of the victims according to DSM-III-R criteria was done by
      weighing and integrating all available information. A series of studies
      addressing the mental disorders among suicide victims, the treatment received
      before death and the life events is now reviewed. Among a random sample of
      suicide victims from the natiowide suicide population, at least one psychiatric
      diagnosis was made for 93% of the victims. The most prevalent disorders were
      depressive syndromes (66%) and alcohol dependence/abuse (43%). The prevalence of
      major depression was higher among women than among men. Major depression as the
      principal diagnosis was more common among the elderly suicides. Among adolescent
      victims, depressive syndromes were also the most prevalent disorders. Adjustment
      disorders were common (25%) among male adolescent suicides. The majority of
      suicide victims of all ages suffered from comorbid mental disorders. Among
      suicide victims who had had contact with a health carer before death, inadequacy
      of treatment for mental disorders seems to have been common. Of the major
      depressive victims only 3% were found to have received adequate
      psychopharmacological treatment, and only 7% received weekly psychotherapy by a
      trained therapist. The analysis of the massive database collected in the research
      phase of the National Suicide Prevention Project in Finland is still ongoing, and
      the implications of the findings for suicide prevention will be refined during
      the research process. The necessity to improve recognition and treatment for
      comorbid depressive disorders in all age groups seems evident already.

PMID- 9179955
TI  - Psychopathology and psychotherapy in the dying AIDS patient.
AB  - AIDS is not yet the problem in Japan that it is in North American, Europe and
      Africa, but at the recent 10th International AIDS Conference held in Japan, it
      was estimated that more Asians will become infected with HIV in the coming year
      than any other population worldwide. Although the majority of these infections
      will occur in Thailand and India, it was estimated that there may be as many as
      15,000 HIV positive individuals in Japan, a number expected to rise to 26,000
      over the next 3 years. Although AIDS is arriving in Japan later, this may give
      society in general and the medical profession in particular, time to learn from
      the experiences and mistakes of those who had a head start in dealing with the
      epidemic. Although this paper deals with the dying AIDS patient, some of the
      issues faced by the therapist working with any population of dying patients will
      be reviewed before focusing more specifically, on some of the particular issues
      seen in working with AIDS patients.

PMID- 9179956
TI  - Psychosocial and spiritual issues in terminal care.
AB  - The author has been working as a psychiatrist over the past 30 years, engaging in
      clinical work and in research. During his career as a psychiatrist the author
      began to develop a special interest in terminal care. This led to additional
      study in a residency program in internal medicine and oncology, and culminated in
      the establishment of a hospice in 1984. Through this close association with
      hospice patients the author has experienced approximately 2000 deaths over the
      past 10 years. These experiences have reinforced in his mind the viewpoints that
      people die as a whole person.

PMID- 9179957
TI  - Grief education and bereavement support in Japan.
AB  - This paper introduces the activities of the Japanese Association for Death
      Education and Grief Counseling, highlighting especially its grief education and
      bereavement support program. Because of greater life expectancy, most women in
      Japan will one day experience the death of their husbands, therefore pre
      widowhood education programs are offered to married women in order to prepare
      them for widowhood. Memorial services, Buddhist, Christian and non-religious, are
      offered for bereaved persons. The search for a new self-identity after
      bereavement, the role of volunteer work, and the search for meaning in loss and
      bereavement are discussed. The issues of disenfranchised grief and grief after
      death from overwork are important themes in grief education.

PMID- 9179958
TI  - Psychological care for the bereaved.

PMID- 9179959
TI  - Dying in dignity: the pros and cons of assisted suicide.
AB  - This paper describes the historical background and the current situation
      regarding the practice of assisted suicide in The Netherlands. It outlines and
      discusses what is considered to be the 'golden standard' of conduct for doctors
      and other health professionals in this area, it describes experiences with the
      application of this standard and discusses some of the major pitfalls involved.
      It also describes the results of several empirical studies on the attitudes of
      the general public, and the nature and magnitude of the practice of assisted
      suicide in the country. It is concluded that although perfect application of the
      'Dutch Protocol' encourages and supports careful and responsible professional
      conduct regarding assisted suicide and provides satisfactory safeguards both for
      the patients involved, (potential) survivors and society as a whole, there are
      many cases where the desired perfection is far from feasible, hence assistance
      with suicide remains very hazardous. It is also concluded, however, that health
      care policy makers, as well as professionals, should confront the issue of
      assisted suicide, since, as the historical development in The Netherlands has
      shown, repression and denial implicates the worst of all possible scenarios, and
      does not contribute at all to the primordial goals of a humane health care
      system: the alleviation of suffering and the prevention of premature death.

PMID- 9179960
TI  - Dignified death: a German perspective.
AB  - After discussing some defining questions concerning dignified death, active and
      passive euthanasia, assisted suicide and the criteria for free will and informed
      consent, the juridical situation in Germany is reported. Passive euthanasia
      according to the patients' free will is accepted, assisted suicide, active
      euthanasia, and passive euthanasia without informed consent are not accepted. The
      ethical discussion on these topics in Germany reveals a spectrum of opinions.
      There is somewhat more emphasis on the cons than on the pros. Humanistic and
      economic arguments merge in the debate. The philosophy of consequentialistic
      utilitarianism is heavily criticized by many authors who warn that respect even
      for the unproductive life must not fade. After some remarks on empirical studies
      on attitudes towards death and the history of attitudes towards euthanasia the
      conclusion lists the arguments, pros and cons, and gives a personal view.

PMID- 9179961
TI  - Ethical orientations and dignified death.
AB  - Dignified death is regarded commonly as a recent social phenomenon as a
      consequence of technological development in medical sciences; the phenomenon
      emerging in developed countries. Two cases were provided to demonstrate that
      dignified deaths have been occurring in Nepal as well as in traditional destitute
      Japan. A difference between the presented cases of dignified death in the
      developing countries and the cases in the developed countries hinges upon the
      relationship the dying perceive vis-a-vis the group they belong to; in the former
      the core of dignity is none other than their altruistic self-sacrifice for the
      continuation of the former the core of dignity is none other than their
      altruistic self-sacrifice for the continuation of their group, whereas in the
      latter no such valued group seems to exist. Two types of ethical orientations
      were postulated to account for the difference, and the coping behavior of
      Japanese-American patients with cancer is shown by the denial of the existence of
      cancer.

PMID- 9179962
TI  - Death with dignity in the Japanese culture.
AB  - In Japanese culture, the concept of death with dignity focuses on enhancing the
      relationship with significant others (especially with family members) and is
      expected to continue even after death, unlike the autonomous decision making in
      Western cultures. Deaths in such relationships are self-worthy, majestic and
      wished for. The author depicts these traits by describing the worship of sudden
      death aspiration in a special temple, the death ceremonies repeated even after
      death which involve even distantly related people, a suicide allusively asking
      for something, and a joint suicide.

PMID- 9179963
TI  - Researches on viral hepatitis markers correlated with pathomorphological and
      clinical aspects in chronic hepatitis.
AB  - A number of 112 patients hospitalized for chronic hepatitis and liver cirrhosis
      were investigated. According to the results of the pathomorphological
      examinations of liver biopsies, 29 (25.8%) were cases of persistent chronic
      hepatitis (PCH), 39 (34.8%) cases of active chronic hepatitis (ACH), and 44
      (39.2%) cases of liver cirrhosis. The prevalence of the female sex was observed
      in PCH (61.6%) and ACH (64.7%) cases, whereas in liver cirrhosis the sex
      distribution was more balanced (53.3% patients were males). The patients' mean
      age ranged from 34 to 38 years in PCH cases, from 44 to 46 years in ACH cases and
      from 50 to 57 years in liver cirrhosis. The postviral cirrhosis was three times
      more frequent in the female sex (77%), while the alcoholic and mixed cirrhoses
      (of an associated alcoholic and viral etiology) were prevalent in males (63.2%,
      respectively 72.2%). Serological tests for detection of the serological markers
      of hepatitis viruses B (HBV), C (HCV) and Delta (HDV) were performed for the
      purpose of studying the correlations between the pathomorphological findings and
      the viral markers. Among the 39 patients with ACH, HBV markers were detected in
      13 cases (33.3%), anti-HCV antibodies in 10 (25.6%), and associated HBV-HCV,
      respectively HBV-HDV infections in 9 (23%) cases (6, respectively 3 patients). In
      the remaining 7 cases (17.9%) of ACH, there were no serological markers in the
      three hepatitis viruses. Of the 29 patients with PCH, 17 cases (58.6%) displayed
      HBV markers, 4 (13.7%) anti-HCV antibodies, in one patient (3.4%) an associated
      HBV-HCV infection was present, and in 7 patients (24.1%) markers of none of the
      three hepatitis viruses could be identified. Of the 44 patients with liver
      cirrhosis, HBV markers were detected in 17 cases (38.6%), anti-HCV antibodies in
      9 (20.4%) and associated HBV-HCV and, respectively, HBV-HDV infections in 11
      cases (25%) (9, respectively 2 cases). In 7 (15.9%) of the 44 patients with
      cirrhosis, markers of none of the three hepatitis viruses could be identified.

PMID- 9179964
TI  - Natural propolis extract NIVCRISOL in the treatment of acute and chronic
      rhinopharyngitis in children.
AB  - In the work there are shown the results of a "case control" study carried out in
      a children collectivity (preschool children and school-children), regarding the
      action of an aqueous propolis extract, NIVCRISOL, in acute and chronic
      inflammatory diseases of the upper airways. The preparation, which had a rich
      content of flavonoids, was administered to a group of preschool children and
      school-children treated during the whole cold season 1994-1995. The monitoring of
      the subgroups investigated was performed by clinical observation of the health
      state and recording of the incidence of symptoms characteristic to acute or
      chronic rhinopharyngeal diseases, as well as by a periodical laboratory
      examination for the detection and characterization of viral, microbial and fungal
      germs carriage. The analysis of the data obtained pointed out the favourable
      effects of this local treatment, expressed by lowering of the number of cases
      with acute or chronic symptoms, and decrease and sometimes suppression of the
      viral-microbial flora carriage of the upper airways. These positive results, the
      good tolerance of the preparation, the advantages of the therapy with natural
      products and more economic criteria entitle us to propose the administration of
      this preparation as an adjuvant medication in the local treatment of some
      clinical forms of acute or chronic rhinopharyngeal diseases.

PMID- 9179965
TI  - Clinical and immunological features of the HIV infection associated with chronic
      hypertrophic parotitis in children.
AB  - The study refers to children of 0-15 years of age, infected with HIV and who
      developed a chronic hypertrophic parotitis (CHP), admitted to the "Colentina"
      Clinic of Infectious Diseases--Paediatrics in Bucharest, between January 1, 1990
      and May 15, 1993. Among the total number of 579 HIV infection cases hospitalized
      in the above-mentioned period, 135 were associated with CHP, hence an incidence
      of 23.3%. The HIV infection was defined by two ELISA-positive assays, confirmed
      by a Western-blot test. No specific laboratory test for the diagnosis of CHP in
      the course of HIV infection was available. The detection of a uni- or bilateral
      painless parotid enlargement, without signs of skin inflammation in HIV-infected
      children, was conclusive for the diagnosis of CHP. IgG type anticytomegalovirus
      antibodies were detected in 41.17% (7/17) and anti-Toxoplasma antibodies in 50%
      of the tested cases (4/8). The immunogram performed in 85 children showed
      increased IgG values in 92.94% of cases (79/85) and increased IgM values in
      85.88% (73/85). There was recorded a significant increase in the levels of
      immunoglobulins, especially of IgM, which exceeded 13 times the normal values.
      The CD8 cells were frequently normal or increased (94.44%, respectively 34/36).
      CHP appeared before a marked deterioration of CD4 cells, simultaneously with the
      CD8 cells proliferation. CHP developed at a stage of the HIV infection when the
      medium-term prognosis was still considered favourable.

PMID- 9179966
TI  - Experimental infections with some pneumotropic viruses in the mouse. Note II.
      Virological and pathomorphological aspects of experimental associated infections
      with parainfluenza virus, adenovirus and respiratory syncytial virus in the
      mouse.
AB  - Associated infections with long-strain parainfluenza virus type 3, adenovirus
      type 3 and respiratory syncytial virus were experimentally induced in white mice.
      They were pointed out by the appearance of homologous serum antibodies, positive
      IF reactions in the pulmonary tissue, and histological, histochemical and
      histoenzymatic lesions, which were more severe than those of controls infected
      with single virus of those mentioned above, since they involved wider areas and
      had a high frequency. The pathomorphological changes made up an inflammatory,
      exudative, alternative and predominantly infiltrative lymphohistiocytic picture,
      mainly pulmonary (diffuse interstitial bronchopneumonia, sometimes with a
      peribronchovascular location, of a cuff-like aspect), hepatic, renal and cardiac,
      but dystrophic processes were also present--hyalinosis of tunica media in the
      lung, hepatocyte cytoplasm vacuolizations on areas of various sizes of lobuli--,
      especially in associated infections with parainfluenza virus type 3 and
      adenovirus type 3. Megakaryocytic hyperplasia in the spleen, present in all the
      experimental models, was also described. Generally, the modified structural
      aspects made up and pointed out a complex pathological process.

PMID- 9179967
TI  - Clinical and epidemiological correlations between the infection with HPV 16 and
      HPV 18 and female cervical lesions.
AB  - A number of 66 specimens from female cervical lesions were examined for infection
      with human papillomavirus (HPV) types 6, 11, 16, and 18 by nucleic acid
      hybridization in dot-blot techniques and 35 sera were tested by the immunodot
      blot technique, in order to detect the presence of anti E4 and E7 HPV protein
      antibodies. The findings were compared with the histologic diagnosis. Fifty-six
      per cent of specimens contained HPV DNA sequences. In 47% of specimens from
      cervical carcinoma, HPV 11 was detected in 4 cases, HPV 16 in 21 cases, and HPV
      18 in 7 cases. Serum antibodies against HPV 16 E4 and HPV 16 E7 occurred in all
      the cases of uterine carcinoma, in 4 of 10 cases of CIN I-II, and in 3 of 5 sera
      obtained from apparently healthy women. The analysis of risk factors disclosed
      the early onset of sexual activity, a relatively high number of births and
      abortions before the age of 22 years, the use of oral oestroprogestative
      contraceptive agents, the presence in anamnesis of genital infections with
      bacterial flora--Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis,
      Mycoplasma, etc. Our results showed that HPV typing by nucleic acid hybridization
      was useful for differentiating low- from high-risk cervical lesions and also
      tried to elucidate the risk factors associated with HPV infections and
      progression to malignancy.

PMID- 9179968
TI  - Blood amounts and suppressive in vitro activity of CD8+11b(+)-lymphocytes from
      HIV-infected children, related to hepatitis B or C virus association.
AB  - In HIV only, as well as in HIV/hepatitis B- and HIV/hepatitis C-infected children
      (6 to 8 years of age), with moderate altered clinical and immune cell markers,
      the total amounts of CD8(+)-set and of CD8+11b(+)-subset (T-suppressor) blood
      lymphocytes, by means of flow cytometry, were determined. On the other hand,
      within several mixtures of autologous sorted CD3+/CD8+11b(+)-cells, the per cent
      reduction of HLA-DR+ expression on T-cells, at different effector/responder cell
      ratios, was appreciated. Significant higher levels of CD8+11b(+)-cells,
      especially in HIV/hepatitis B virus groups, were found, that correlated with a
      stronger suppressive activity. The strongest alteration of immune markers, within
      HIV-seropositive, HBs+, HBe+ patients, was noticed. A possible usefulness of
      these data in HIV only, and in HIV-associated hepatitis B or C virus
      contamination, during pediatric AIDS monitoring, was commented.

PMID- 9179969
TI  - Specific targeting of human papillomavirus type 16 E7 oncogene with triple-helix
      forming purine oligodeoxyribonucleotides.
AB  - Molecular mechanical calculations (computer modelling), optical DNA melting
      experiments and co-migration assay were used to assess stable helix formation at
      homopurine--homopyrimidine-rich target sites present in the human papillomavirus
      type 16 E7 oncogene (positions 656-673 on the genome map). The target sequence,
      either present in the E7 oncogene obtained by PCR technique or prepared from
      oligodeoxyribonucleotides (ODNs), can be specifically recognised by different 17
      merpurine ODNs designed to form antiparallel or parallel triple helices. These in
      vitro experiments realised with rather long purine ODNs having a high degree of
      specificity open the way for in vivo tests focused on E7 oncogene targeting and
      suppression.

PMID- 9179970
TI  - Intraepithelial lesions of the urinary bladder with a discussion of the
      histogenesis of urothelial neoplasia.
AB  - Bladder neoplasia of the transitional cell type progresses by two distinct, but
      occasionally interrelated, pathways characterized morphologically by a papillary
      or nonpapillary configuration. In this review, the authors discuss
      intraepithelial lesions of the urinary bladder, le, those lesions confined within
      the basement membrane of the urothelium. The emphasis is on histogenesis of
      bladder neoplasia, its putative precursor lesions, and its noninvasive forms.
      Areas of controversies are highlighted, and the pertinent clinical features,
      histological findings, and biological potential of these lesions examined.

PMID- 9179971
TI  - Carcinoma of the urinary bladder: a review of its diverse morphology.
AB  - The microscopic appearances of carcinomas of the urinary bladder are reviewed,
      with emphasis on patterns that have been highlighted only recently or account for
      major problems in differential diagnosis. Approximately 80% of bladder cancers
      are of urothelial (transitional cell) type. The major new information pertaining
      to that category is the appreciation of the extent to which they may have unusual
      patterns that, on occasion, lead to their misinterpretation as benign. The
      homology between some of these variants and benign epithelial abnormalities is
      emphasized and helps in understanding them: nested carcinomas and von Brunn's
      nests, small tubules and nephrogenic adenoma, carcinomatous glands and cystitis
      glandularis, cystic carcinomas and cystitis cystica. Other peculiar patterns seen
      in urothelial carcinoma include silt-like spaces, clefts, and angulated nests
      with spikes. Differences in opinion have been apparent in recent contributions
      concerning carcinomas of the bladder with a prominent component of spindle cells
      (sarcomatoid carcinomas) and whether they represent a category distinct from
      carcinosarcoma. Irrespective of this academic distinction, the potential for some
      epithelial-derived tumors of the bladder to be dominated by or even have an
      exclusive component of spindle cells is important. Three other major categories
      of primary bladder cancer are squamous cell carcinoma, adenocarcinoma, and
      undifferentiated carcinoma. The differences in the frequency of subtypes of
      adenocarcinoma originating in the bladder mucosa and urachus has recently been
      emphasized, as has the spectrum of undifferentiated carcinomas. In some bladder
      cancers, the stroma has unusual features. These are carcinomas with
      pseudosarcomatous stroma, osseous or cartilaginous metaplasia, or osteoclast-type
      giant cells. The diversity of appearances of bladder cancer has important
      implications in differential diagnosis.

PMID- 9179972
TI  - Pathologic prognostic parameters in bladder urothelial biopsy, transurethral
      resection, and cystectomy specimens.
AB  - Pathologists play an important role not only in diagnosing bladder tumors but
      also in reporting features important in determining prognosis. In this article,
      the authors review histopathologic features that may help determine prognosis
      including depth of invasion, grade of tumor, multicentricity, tumor size, and
      presence of (1) carcinoma in situ, (2) variant histological patterns, and (3)
      lymphatic and vascular invasion. The biology of bladder tumors is being
      extensively studied, and newer prognostic factors based on these molecular
      studies are emerging, some of which appear to show prognostic significance in
      limited clinical reports. Such factors as blood group antigen expression,
      proliferative indices, molecular markers, and new proposed techniques are
      discussed.

PMID- 9179973
TI  - Alterations of tumor suppressor genes in bladder cancer.
AB  - The etiopathogenesis of neoplastic diseases is characterized by its multiple
      nature. Multiple biological and physical agents have been identified as
      initiating or promoting neoplastic mechanisms. However, they all appear to have
      common molecular basis, granting genetic instability and causing somatic
      derangements to preneoplastic and tumor cells. Target genes implicated in
      cellular transformation and tumor progression have been divided into two
      categories: proto-oncogenes (that when activated become dominant events
      characterized by gain of function) and tumor suppressor genes (recessive events
      characterized by the loss of function). Alteration in proto-oncogenes and tumor
      suppressor genes seem equally prevalent among human cancers. Multiple mutations
      appear to be required to conform the malignant phenotype. It is, therefore,
      conceivable to view cancer as fundamentally a genetic disease entailing inherited
      (also called "germline") or acquired (also termed "somatic") mutations of genes
      in these two categories. The concept of tumor suppressor genes was established in
      studies with somatic cell hybrids, revealing that when malignant cells were fused
      with normal cells some of the hybrids were nontumorigenic. Clinically, the
      existence and relevance of this category of genes was based on epidemiological
      studies of the intraocular childhood tumor retinoblastoma, and it was postulated
      that two independent events were needed to inactivate a given gene. It was
      further shown that, in general, that was achieved by an allelic loss followed by
      a point mutation of the remaining allele. A family of genes has been
      characterized that follows this "two-hit" model including the two prototype
      suppressors genes: the retinoblastoma (RB) and the TP53 (also known as p53)
      genes. These genes encode a variety of molecules with distinct biological
      properties, including cell cycle regulation and cellular differentiation.
      Germline and somatic mutations of these genes appear to be the most common
      abnormalities found in human cancer including bladder neoplasms. More recent
      studies have shown that inactivation of some of these genes (i.e., TP53) occurs
      in bladder tumors that have a more aggressive clinical outcome and poor
      prognosis. In the following subheadings, the authors have reviewed the molecular
      abnormalities associated with these recessive genes in bladder tumors and discuss
      the potential clinical use of their detection. The implementation of objective
      predictive assays to identify these alterations in clinical material will enhance
      the ability to assess tumor biological activities and to design effective
      treatment regimens. The need now is to translate this newly developed scientific
      knowledge into diagnostic and therapeutic strategies, which, in turn, will
      enhance quality of life and prolong patient survival.

PMID- 9179974
TI  - Pseudoneoplastic lesions of the urinary bladder and urethra: a selective review
      with emphasis on recent information.
AB  - Selected tumor-like lesions of the urinary bladder and urethra, particularly
      those that have been the subject of recent attention in the literature, are
      reviewed. Within the category of epithelial abnormalities, it has recently been
      appreciated that cystitis glandularis of the intestinal type is occasionally
      associated with prominent mucin extravasation into the stroma, a finding that
      should not lead to the misdiagnosis of adenocarcinoma. Additionally, the problems
      that nephrogenic adenoma may cause have been the subject of recent study, and a
      detailed microscopic analysis of this lesion has shed light on the relative
      frequency of its common, and uncommon, features. Within the category of tumor
      like lesions of the bladder, the inflammatory pseudotumor has been the subject of
      much interest as have mullerian lesions. It has recently been appreciated that
      endosalpingiosis is rarely seen at this site, usually in association with
      endocervicosis or endometriosis, leading to the suggested usage of the
      designation "mullerianosis." Selected other tumor-like lesions of the urinary
      bladder and urethra are also reviewed, including the problems nephrogenic adenoma
      may cause when it involves the prostatic urethra in men or a urethral
      diverticulum in females as well as the peculiar stromal cells that have recently
      been described within some urethral caruncles.

PMID- 9179975
TI  - Primary carcinomas of the urethra.
AB  - Urethral carcinomas are rare, and information reported in the literature is
      relatively limited. In this review, the authors present separate discussions on
      the pathology of carcinomas occurring in men and women with emphasis on the
      diverse histological subtypes. Because tumor type and prognosis correspond to
      anatomic location, normal anatomy and histology have been given due
      consideration. Of particular note in the recent literature is an expanded
      experience with clear cell carcinoma, a distinctive tumor primarily of the female
      urethra that has generated considerable interest with respect to its prognosis
      and relationship to urethral diverticulum. The authors use this review to
      illustrate several features of the pathology of these neoplasms synthesize the
      literature, and place into perspective the clinical, pathological, and prognostic
      features.

PMID- 9179976
TI  - The validity and power of tests for equality of two correlated proportions.
AB  - With measurements taken on subjects over time, on matched pairs of subjects or on
      clusters of subjects, the data often contain pairs of correlated dichotomous
      responses. McNemar's test is perhaps the best known test to compare two
      correlated binomial proportions. The salient feature of McNemar's test is that we
      compute the variance of the contrast estimator under the restriction that the
      null hypothesis is true. Wald's test, on the other hand, does not require that
      restriction. As a consequence, Wald's statistic is always greater in magnitude
      than McNemar's statistic when the marginal proportions are unequal, but there is
      a problem with the validity of both McNemar's test and Wald's test with small to
      moderate samples. There have been various modifications suggested for McNemar's
      test to improve its performance. We propose a modified Wald's test that is valid
      in small to moderate samples and maintains good power. We also evaluate the
      performance of McNemar's test and Wald's test with and without modifications to
      enhance validity as well as the performance of the large sample likelihood ratio
      test and an exact test of the equality of correlated binomial proportions. In a
      smaller study, we compare the behaviour of a test based on the James-Stein
      estimator of the common odds ratio proposed by Liang and Zeger to McNemar's test
      and Wald's test.

PMID- 9179977
TI  - Conceptual aspects of attributable risk with recurrent disease events.
AB  - The concept of attributable risk is extended to cover disease events which are
      potentially recurrent. Whereas the conventional attributable risk parameter
      allows quantification of the proportion of diseased individuals due to a certain
      risk factor, the parameter introduced here quantifies the proportion of disease
      events which is attributable to a specific exposure variable. We accomplish this
      by taking into account not only the probability of ever being affected by the
      disease but also the exposure-specific number of occurrences of the disease event
      within a defined time period. Practical examples highlighting the relevance of
      the new measure are presented. Various representations of the parameter are given
      and methods are proposed to adjust this new measure for confounding and effect
      modification. Point estimates of the parameter and their asymptotic variances are
      derived under different distributional assumptions. Advantages and limitations of
      this new approach for assessing the public health impact of an exposure for
      recurrent disease event are discussed.

PMID- 9179978
TI  - Bayesian inference in two-phase prevalence studies.
AB  - This paper discusses Bayesian methods for the assessment of the prevalence of a
      disorder based on data from a two-phase design with a short screening instrument
      administered at the first phase followed by an in-depth diagnostic instrument
      given at the second phase. In calculating the posterior distributions of the
      quantities of interest, for example, the prevalence, sensitivity and specificity,
      and predictive distributions, we used the Gibbs sampler. We illustrate our
      approach by assessing the prevalence of depression in adolescents with use of
      data attained from a two-phase design.

PMID- 9179979
TI  - A population approach to initial dose selection.
AB  - Before a drug can be marketed, an initial dose must be established. Sheiner et
      al. argue that a population approach leads to the most informed and rational
      decision making. We discuss the choice of an initial dose from both a predictive
      and estimative viewpoint. Our criteria are based upon evaluating the
      probabilities that a patient from the specified population obtains a response
      that is at least of a specified size. We demonstrate the approach using a
      simulation study and compare estimation of population parameters and initial dose
      using Bayesian and likelihood-based methods.

PMID- 9179980
TI  - Comparison of non parallel immunoassay curves resulting from mixtures of
      competing antigens.
AB  - Relative potency is a measure that has been used for many years to summarize the
      comparison of dose-response curves in parallel line bioassays. When response
      curves for two preparations are not parallel the traditional definition of
      relative potency no longer applies. We review the concept of relative potency and
      show that, in some situations, it can be given meaning for non-parallel curves as
      the ratio of biological activity in full strength assay preparations. Under an
      assumption that non-parallel curves result from the competition of mixtures of
      antigens for receptor binding sites, estimation of relative potency for non
      parallel curves can be accomplished. We show that estimation of models for both
      parallel curve and response attenuation situations may be accomplished within the
      framework of generalized linear models. This estimation depends on the ability to
      deal with non-linear parameters appearing in the link function, and an iterative
      algorithm depending on direct parameter updates is outlined. The topics discussed
      are illustrated with the analysis of data from two immunoassays conducted with
      veterinary vaccines. The models developed here depend in an essential way on the
      assumption of response attenuation by competing antigens. Our methods may not be
      appropriate for non-parallel curves caused by other phenomena.

PMID- 9179981
TI  - Prediction bounds for random shelf-lives.
AB  - Every drug product requires indication of a shelf-life on the immediate container
      label. The labelled shelf-life is usually determined by a stability analysis with
      several batches of the drug product. Because of the existence of batch-to-batch
      variation, the true shelf-lives of different batches differ and can be treated as
      random variables. To obtain a single labelled shelf-life applicable to all future
      batches of the drug product, we propose to use a prediction bound of the random
      shelf-life of a future batch. Under some assumptions, the proposed labelled shelf
      life (prediction bound) is lower than the true random shelf-life with a
      probability approximately equal to a pre-assigned level. For illustration, we
      provide an example concerning a new drug application stability analysis conducted
      in a pharmaceutical company. We also discuss an application of our technique to
      the problem of clean-up of contaminated soils.

PMID- 9179982
TI  - Rule-based ranking schemes for antiretroviral trials.
AB  - Endpoints are a continuing source of controversy in clinical trials of
      antiretroviral (specifically, anti-HIV) treatments. The most visible disagreement
      is about the respective roles of morbidity and mortality as endpoints, and
      laboratory measurements as endpoints. Laboratory measurements have been intensely
      examined as possible surrogates for clinical outcomes, but the definition of the
      usual clinical outcome-first occurrence or recurrence of an AIDS-defining
      condition or death-has received little critical scrutiny. First disease
      progression has serious weakness as an endpoint, and one should consider
      alternatives. In this paper, we suggest using rule-based schemes to rank
      patients' post-randomization histories and then using the ranks as an outcome
      measure, an extension of the work by Follmann et al. on heart disease. We
      evaluated six rule-based ranking schemes for antiretroviral trials by applying
      them to 60 participants in CPCRA 002 and comparing the results to subjective
      rankings given by five experts. The expert's rankings were in good agreement with
      each other, and the six rule-based schemes were clearly differentiated by their
      degree of agreement with the expert's rankings. The ranking scheme most in accord
      with the experts ranked patients first by seriousness of their most serious AIDS
      defining disease, second by the timing of that disease, and the third by the
      total number of AIDS-defining diseases they experienced. Finally, we used this
      rule-based rankings to re-analyse CPCRA 002.

PMID- 9179983
TI  - A hierarchical approach to inferences concerning interobserver agreement for
      multinomial data.
AB  - We consider inference methods for interobserver agreement studies characterized
      by two raters and several outcome categories that one can naturally combine to
      address a series of questions of a priori interest. We propose a new method based
      on a series of nested, statistically independent inferences, each corresponding
      to a binary outcome variable obtained by combining a substantively relevant
      subset of the original categories. We conduct the inferences using a goodness-of
      fit procedure that extends the approach of Donner and Eliasziw. The methodology
      presented is an alternative to methodology that places each of the outcome
      categories on an equal footing in estimating interobserver agreement for
      multinomial data. We provide two examples.

PMID- 9179984
TI  - Intestinal UDP-glucuronosyltransferase activities in rat and rabbit.
AB  - 1. Tissues other than the liver can contribute significantly to the drug
      metabolizing capacity of an animal. In the current study, the glucuronidation of
      several aglycones in microsomes from the small intestinal mucosa of rat and
      rabbit has been investigated and compared with glucuronidation in liver
      microsomes. 2. UDP-glucuronosyltransferase activities in intestinal microsomes
      were generally higher in rabbit when compared with rat, ranging from 200 to 300%
      for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4
      hydroxybiphenyl. 3. In contrast, hepatic activities were much higher in rat than
      in rabbit, ranging from 300 to 400% for 1-naphthol, 2-naphthol, 4
      methylumbelliferone, 2-hydroxybiphenyl and testosterone; and from 150 to 250% for
      4-nitrophenol and diclofenac. 4. In rabbit, activities in the small intestinal
      mucosa were comparable (70-100%) with hepatic activities for most aglycones. In
      rat, intestinal mucosa activities were much lower than in liver, with activities
      toward 1-naphthol, 2-naphthol, 4-nitrophenol, 4-methylumbelliferone, 2
      hydroxybiphenyl and 4-hydroxybiphenyl in the small intestine representing 5-15%
      of hepatic activities. 5. With a higher intestine:liver activity ratio,
      intestinal UDP-glucuronosyltransferases could be anticipated to contribute more
      to overall drug glucuronidation in rabbit as compared with rat, thereby
      contributing more to reducing drug bioavailability.

PMID- 9179985
TI  - In vitro metabolism of the new insecticide flupyrazofos by rat liver microsomes.
AB  - 1. The in vitro metabolism of the new insecticide flupyrazofos was studied using
      rat liver microsomes. Two metabolites were produced and identified as O,O-diethyl
      O-(1-phenyl-3-trifluoromethyl-5-pyrazoyl) phosphoric acid ester (flupyrazofos
      oxon) and 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (PTMHP) based on UV and
      mass spectral analysis. 2. Cytochrome P450 oxidatively converted flupyrazofos to
      flupyrazofos oxon, a major metabolite and phenobarbital-induced microsomes
      increased this desulphuration by 8-fold. 3. Flupyrazofos oxon was converted to
      PTMHP with a half-life of 47.8 min by chemical hydrolysis and this conversion
      also proceeded non-enzymatically under our microsomal incubation conditions.

PMID- 9179986
TI  - In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver
      microsomes and liver slices.
AB  - 1. The metabolic profile of D-23129, a new anticonvulsant agent, was studied in
      vitro using human liver microsomes and fresh liver slices. 2. Oxidative
      metabolism appeared to be minimal with D-23129. The percent mean total
      radioactivity not associated with the parent compound recovered from oxidative
      metabolism studies from three individual liver donors was 0.7% +/- 0.6 SD and was
      not significantly different from [14C]-D-23129 incubated with heat inactivated
      microsomes, mean = 0.5% +/- 0.4 SD. 3. Phase II conjugation dominated the
      metabolism of D-23129 producing two distinct N-glucuronides as the primary
      metabolites. These metabolites were identified by electrospray ionization LC/MS.
      4. The apparent Km for one of the glucuronide metabolites was determined in human
      liver microsome preparations from two individual liver donors to be 131 and 264
      microM respectively, Vmax determined for the same microsomal preparations yielded
      48.9 and 59.9 pmol/min/mg protein.

PMID- 9179987
TI  - Molecular modelling of mammalian CYP2B isoforms and their interaction with
      substrates, inhibitors and redox partners.
AB  - 1. The construction of three-dimensional models of CYP2B isozymes from rat
      (CYP2B1), rabbit (CYP2B4) and man (CYP2B6), based on a multiple sequence
      alignment with CYP102, a unique eukaryotic-like bacterial P450 (in terms of
      possessing an NADPH-dependent FAD- and FMN-containing oxidoreductase redox
      partner) of known crystal structure, is reported. 2. The enzyme models described
      are shown to be consistent with experimental evidence from site-directed
      mutagenesis studies, antibody recognition sites and amino acid residues
      identified as being associated with redox partner interactions, together with the
      location of a key serine residue (Ser-128) likely to be involved in protein
      kinaseA-mediated phosphorylation. 3. A substantial number of known substrates and
      inhibitors of CYP2B isozymes are shown to fit the putative active sites of the
      enzyme models in agreement with their reported position of metabolism or mode of
      inhibition respectively. In particular, there is complementarity between the
      characteristic non-planar geometries of CYP2B substrates and key groups in the
      enzymes' active sites. 4. Molecular modelling of CYP2B isozymes appears to
      rationalize a number of the reported findings from quantitative structure
      activity relationship investigations on series of CYP2B substrates and
      inhibitors.

PMID- 9179988
TI  - Drug disposition of incadronate, a new bisphosphonate, in rats with bone
      metastases.
AB  - 1. Drug disposition of incadronate in the nude rat with bone metastases induced
      by A375 human melanoma cells was studied after intravenous administration. 2. The
      pharmacokinetics of incadronate (plasma concentration, urinary excretion and bone
      uptake) in rat with bone metastases was not markedly different from that in the
      control rat. This compound, however, was selectively taken up in the bone region
      around metastatic tumour nests. 3. Drug concentrations in the bone region around
      tumour nests were 3-10 micrograms/g, these levels being higher than the IC50
      (0.35 microgram/ml) for the inhibitory effect of this drug on osteoclasts in
      vitro. 4. In contrast, concentrations in the tumour nest itself was < 0.7
      microgram/g, being markedly lower than the IC50 (35 micrograms/ml) for the
      inhibitory effect on the proliferation of tumour cells in vitro. 5. These results
      strongly suggest that pharmacological action of incadronate in mouse with bone
      metastases (inhibitory effect on the growth of metastatic tumour in bone) is
      caused not by the direct action on the tumour cells but by the distribution of
      the drug in the perifocal bone region followed by inhibition of the activity of
      osteoclasts, resulting in inhibition of the osteolytic process, which is
      necessary for the progress of metastatic tumour.

PMID- 9179990
TI  - Biological fate of sulphur mustard: identification of valine and histidine
      adducts in haemoglobin from casualties of sulphur mustard poisoning.
AB  - 1. Analytical methods were developed for the detection of N-terminal valine and
      histidine adducts in haemoglobin alkylated with sulphur mustard. 2. N-(2
      hydroxyethylthioethyl)-N-terminal valine was selectively cleaved from globin with
      the Edman reagent pentafluorophenyl isothiocyanate. The resulting thiohydantoin
      derivative was analysed by high resolution gc-ms using negative ion chemical
      ionization. An alternative procedure, involving acid hydrolysis of globin to its
      constituent amino acids and conversion of the adduct to its di-TBDMS derivative,
      was less sensitive. 3. N-(2-hydroxyethylthioethyl)histidine was analysed, after
      acid hydrolysis of globin, as its fluorenylmethyloxycarbonyl derivative by lc-ms
      ms using electrospray ionisation and selected reaction monitoring. 4. N-(2
      hydroxyethylthioethyl)valine and (2-hydroxyethylthioethyl)histidine were detected
      in globin isolated from a rat treated percutaneously with sulphur mustard, and in
      globin from five blood samples collected from human casualties of sulphur mustard
      poisoning. The adducts are proposed as biological markers of sulphur mustard
      poisoning. in addition to urinary metabolites and DNA adducts.

PMID- 9179989
TI  - Improvement of bioavailability of the HIV protease inhibitor SC-52151 in the
      beagle dog by coadministration of the CYP3A4 inhibitor, ketoconazole.
AB  - 1. SC-52151, an HIV protease inhibitor, is mainly metabolized by CYP3A4 and is
      poorly bioavailable after oral administration. After i.v. administration of SC
      52151 to the female beagle dog (2.5 mg/kg), SC-52151 was rapidly eliminated in
      plasma with an elimination half-life of about 1 h, a plasma clearance of 44
      ml/min/kg and an apparent steady-state volume distribution of 2.2 litre/kg. The
      high value of plasma clearance of SC-52151 suggests an extensive hepatic first
      pass metabolism since SC-52151 is highly protein bound and does not partition
      itself into red blood cells. 2. The extensive hepatic first-pass metabolism was
      reduced by coadministration of a CYP3A4 inhibitor, ketoconazole. 3. Dogs were
      dosed daily with ketoconazole at dose of 100 mg ketoconazole per dog
      (approximately 10 mg/kg) for 5 days prior to the initiation of coadministration
      of SC-52151 for 15 days. The doses used for SC-52151 was 0, 60 and 120 mg SC
      52151/kg/day (divided t.i.d., 8-h dosing interval). Coadministration of
      ketoconazole improved the bioavailability of SC-52151 from 4.1 to 9.6% and also
      improved the Cmax of SC-52151 from 0.41 to 0.83 microgram/ml. 4. Although the
      absolute bioavailability of SC-52151 was still low (approximately 10%), the Cmax
      and AUC achieved in this study were satisfactory for conducting chronic
      toxicology studies. No toxicity associated with the coadministration of
      ketoconazole was evident. Results from this study suggest that coadministration
      of ketoconazole might be a practical approach to increase the exposure of SC
      52151 in both preclinical and clinical studies.

PMID- 9179991
TI  - Pharmacokinetics and pharmacodynamics in toxicology.
AB  - 1. Pharmacokinetics aids interpretation of the dose-response relationship in
      individual toxicology studies. 2. When used to compare across studies, even in a
      single species other factors, including variation in pharmacodynamic response,
      must be taken into account. Variation in pharmacodynamic response becomes more
      profound when one compares across species. 3. Examples do occur where plasma
      concentration-response relationships are constant across species, particularly
      when corrected for unbound drug. These examples should not be taken as support,
      however, of a general universal principle. 4. Owing to multiple factors such as
      species differences in receptors, enzymes and ion channels, dose or plasma
      concentration-response relationships can vary enormously across species. In the
      light of this, the results of toxicology studies should be viewed as qualitative
      rather than quantitative. Once sufficient clinical experience is gained the human
      database is the overriding measure of drug safety.

PMID- 9179992
TI  - Hepatic enzyme induction and mutagenicity of airborne particulate matter from
      Santiago, Chile in the nourished and malnourished rat.
AB  - 1. Respirable, airborne particles in the ambient air in downtown Santiago, Chile,
      have been characterized for the seasonal variation in total polycyclic aromatic
      hydrocarbon content, 13 of which have been identified including the mutagens
      (benzo(a)pyrene, dibenzo(a,h)anthracene, benzo(a)anthracene, benzo(b)fluoranthene
      and indeno(1,2,3, c,d)pyrene amongst others. 2. Organic extracts derived from
      these particles were administered to both the nourished and malnourished rat and
      resulted in modulation of the hepatic mixed function oxidase system including
      induction of NADPH-cytochrome P450 reductase, cytochrome P4501A as determined by
      Western blot analysis and the associated ethoxyresorufin O-deethylase and aryl
      hydrocarbon hydroxylase activities. 3. The cytochrome P4504A1-dependent 12
      hydroxylation of lauric acid was induced in the malnourished state, but this
      activity was significantly inhibited by treatment of the animals with particle
      extracts in both nutritional states. 4. The particle extracts contained both
      direct and indirect-acting mutagens in the Ames test, and depending on the
      relative complement of both, resulted in either increased or decreased
      mutagenicity in the presence of S9 activation systems derived from both nourished
      and malnourished animals. 5. These results are discussed in the context of the
      interindividual risk assessment of airborne, particulate matter to man.

PMID- 9179993
TI  - Inhibitors of sterol synthesis. Synthesis and spectral properties of 3 beta
      hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one.
AB  - 3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one (4) has
      been prepared as part of a program to synthesize 15-ketosterols that are not
      readily metabolized to cholesterol or side-chain oxygenated species.
      Saponification of 3 beta-acetoxy-5 alpha-chola-8(14),23-dien-15-one (5) followed
      by lithium-ammonia reduction with a bromobenzene quench gave 3 beta-hydroxy-5
      alpha-chol-23-en-15-one (6). Addition of (CF3)2CFI to 6 in the presence of
      triethylborane gave an iodide preparation, which was reduced to 4 with
      tributyltin hydride (71% overall yield of 4 from 5). The 23-iodide preparations
      consisted of 6:1 mixtures of (23R)-3 beta-hydroxy-23-iodo-25,26,26,26,27,27,27
      heptafluoro-5 alpha-cholestan-15-one (9a) and its C-23 epimer 9b with variable
      amounts of 4. Compound 4 was also prepared by lithium-ammonia reduction of the
      delta 8(14) analogs of 4 and iodides 9a and 9b. The presence of small amounts of
      6 in the latter product suggested a side reaction involving cleavage of the C24
      C25 bond with loss of a (CF3)2CF radical. Also prepared were 25,26,26,26,27,27,27
      heptafluoro-5 alpha-cholestane-3 beta, 15 alpha-diol, its 15 beta epimer, the 7
      alpha-methyl analog of 4, 3 beta-hydroxy-7 alpha-methyl-5 alpha-cholestan-15-one
      (16), and (25R)-3 beta,26-dihydroxy-5 alpha-cholestan-15-one. Full 1H and 13C-NMR
      data of high precision with complete signal assignments are given for all new
      compounds. Definitive 1H-NMR stereochemical assignments of the C-24 protons were
      established for most sterols with a C8H17 side chain based on analysis of the
      downfield H-24 resonance in a 750-MHz spectrum of 16. Detailed electron-impact
      mass spectral data are presented together with a summary of major fragmentation
      patterns for 15-hydroxy- and 15-ketosteroids with and without a delta 8(14) bond.

PMID- 9179994
TI  - The pretransition of dipalmitoyllecithin bilayers as probed by the fluorescent
      pyrrolopyrimidine, U-104067.
AB  - The amphiphilic pyrrolopyrimidine, U-104067, is a fluorophore ideally suited to
      report on the relative hydrophobicities of different microenvironments. It forms
      stable monomolecular layers at the air/water interface with a limiting molecular
      area of 51.9 +/- 0.3 A2/molecule and a collapse pressure of about 18 dyn/cm.
      Differential scanning calorimetry of its mixed liposomes with dipalmitoyllecithin
      shows full solubility of the compound in the liquid disordered phase and
      insolubility in the solid ordered phase. In aqueous solutions, the compound binds
      to phospholipid bilayers with a stoichiometry of 13.2 +/- 1.2 moles of lipid per
      mole of U-104067, with Kd = 0.33 +/- 0.05 microM toward egg
      lecithin/phosphatidylserine bilayers and Kd = 1.5 +/- 0.3 microM toward pure egg
      lecithin bilayers. In liquid crystalline phospholipid bilayers the compound
      behaves as two independently emitting species, one accessible to acrylamide and
      the other one not. Doxyl fatty acid methyl esters quench both species and show
      that the average position of the fluorophore is at a depth corresponding to that
      of the 7th carbon of a fatty acyl chain. Dissolved in the liquid disordered (L
      alpha) phase of dipalmitoyllecithin at 45 degrees C, U-104067 shows a single
      ionizable group, pKa = 3.19 +/- 0.03 while in the solid ordered (L beta) phase it
      displays two ionizable groups, pKa1 = 4.99 +/- 0.10 and pKa2 = 6.96 +/- 0.13. The
      most unusual property of this molecule is that it is miscible with the tilted (L
      beta) and liquid (L alpha) phases of dipalmitoyllecithin but totally immiscible
      with the rippled (P beta) phase. Because of this, U-104067 is a sensitive
      reporter for the tilted/rippled phase transition as monitored by its fluorescence
      anisotropy and its quantum yield changes.

PMID- 9179996
TI  - Syntheses of 1,2-di-O-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and analogs
      with 13C- and 2H-labeled choline head groups.
AB  - The syntheses of four head group labeled analogs of 1,2-di-O-palmitoyl-sn-glycero
      3-phosphocholine (DPPC) (6) by a general method from 1,2-di-O-palmitoyl-sn
      glycero-3-phosphatidic acid (5) have been performed. The syntheses of 1,2-di-O
      palmitoyl-sn-glycero-3-phospho[alpha-13C]choline (6a) and 1,2-di-O-palmitoyl-sn
      glycero-3-phospho[beta-13C]choline (6b) were performed from labeled [1
      13C]glycine (1a) in 52% overall yield and from [2-13C]glycine (1b) in 56% overall
      yield, respectively. 1,2-Di-O-palmitoyl-sn-glycero-3-phospho[N(C2H3)3]choline (9)
      was prepared from 2-aminoethanol in 39% overall yield. 1,2-Di-O-palmitoyl-sn
      glycero-3-phospho[alpha-C2H2]choline (12) was prepared from N,N-dimethylglycine
      ethyl ester in 50% overall yield.

PMID- 9179995
TI  - Langmuir monolayer characterization of metal chelating lipids for protein
      targeting to membranes.
AB  - Targeting and organization of proteins on lipid membranes led to applications in
      both biological and materials sciences. Coordination of membrane-bound metal ions
      by surface histidine residues provides a general method for targeting of proteins
      to membrane surfaces. Here we report the Langmuir monolayer properties of a new
      class of metal-chelating lipids. The lipids utilize the metal chelator
      iminodiacetate (IDA) as the hydrophilic headgroup, allowing display of divalent
      transition metal ions on the aqueous side of the membrane. Changes in surface
      pressure-molecular area isotherms were used to observe metal binding, and an
      association constant for Cu2+ binding to the IDA lipids of 10(7-8) M-1 was
      estimated. The ability to control binding site density is important for many
      applications. The IDA lipid was found to be miscible with both
      distearoylphosphocholine (DSPC) and 1-stearoyl-2-oleoyl-phosphocholine (SOPC) at
      most compositions and surface pressures.

PMID- 9179997
TI  - Vagal regulation of heart rate in the prediction of developmental outcome for
      very low birth weight preterm infants.
AB  - To investigate heart rate and respiratory sinus arrhythmia (RSA) as markers of
      developmental outcome, infant ECG and 3 year outcome were assessed in 41 very low
      birth weight (< 1,500 g) infants. Measures of mean heart rate and RSA, and the
      maturational shifts in their values from 33 to 35 weeks gestational age, were
      recorded. RSA measures predicted 3 year outcome beyond the effects of birth
      weight, medical risk, and socioeconomic status. Higher RSA was associated with
      better social skills, whereas greater RSA maturation was associated with better
      mental processing and gross motor skills. Lower heart rate was associated with
      better behavior regulation and social skills, whereas greater maturational
      decreases were associated with better gross motor skills. Dividing the sample
      into groups of infants with birth weights less than 1,000 g and those with birth
      weights over 1,000 g, RSA maturation emerged a strong predictor of mental
      processing, knowledge base, and gross motor skills in the former. A measure of
      joint maturation of RSA and heart rate was associated with better behavior
      regulation at 3 years, as measured by Child Behavior Checklist and Parenting
      Stress Index scores, for this group. The findings directly respond to the need
      for physiological variables in the prediction of outcome in high-risk infants.

PMID- 9179999
TI  - Restricting a familiar name in response to learning a new one: evidence for the
      mutual exclusivity bias in young two-year-olds.
AB  - Children under 2 1/2 years old tend to interpret novel words in accordance with
      the Mutual Exclusivity Principle, but tend not to reinterpret familiar words this
      way. Because alternative principles have been proposed that only predict the
      novel word effects, and because tests of the familiar word effects may have been
      flawed, a new test was administered. In Experiment 1 (N = 32), 24- to 25-month
      olds heard stories in which a novel noun was used for an atypical exemplar of a
      familiar noun. When asked to select exemplars of the familiar noun, they showed a
      small but reliable tendency to avoid the object from the story. In Experiment 2
      (N = 16), the novel nouns in the stories were replaced by pronouns and proper
      names, and the children did not avoid the story object in the test of the
      familiar noun. Thus, the aversion to this object that was observed in Experiment
      1 was not due to its greater exposure or its being referenced immediately before
      testing, but to toddlers' Mutual Exclusivity bias. Their bias is hypothesized to
      be a form of implicit probabilistic knowledge that derives from the competitive
      nature of category retrieval.

PMID- 9179998
TI  - Recognition of the mother's face by six-month-old infants: a neurobehavioral
      study.
AB  - Event-related potentials (ERPs) were recorded from 6-month-olds as each watched
      pictures of the mother's face and a stranger's face. The ERPs differed for the 2
      faces, but the pattern of neural activity elicited depended on whether the mother
      and stranger looked different (Experiment 1, n = 22) or alike (Experiment 3, n =
      22). In contrast, when different 6-month-olds were each shown 1 of these 44 pairs
      of faces their ERPs did not differ between the 2 faces (Experiment 2, n = 22, and
      Experiment 4, n = 22). In a visual preference test of recognition, infants showed
      no evidence of recognizing the mother's face (Experiment 5, n = 32). Together,
      these results suggest that infants are able to recognize their mothers' faces but
      (1) the neural processes accompanying recognition depend on the difficulty with
      which mother can be discriminated from stranger and (2) under the conditions
      investigated in this study, ERPs are a more sensitive measure of recognition than
      is looking time.

PMID- 9180000
TI  - Language and Williams syndrome: how intact is "intact"?
AB  - It has been claimed that Williams syndrome (WS), a rare neurodevelopmental
      disorder, is characterized by serious cognitive deficits alongside intact
      language. The syndrome is often used as a prime example of the modularity of an
      innate faculty for morphosyntactic rules. We challenge this claim and hypothesize
      that morphosyntax, although surprisingly good given WS level of mental
      retardation, is by no means intact. We make an initial test of this hypothesis
      through an analysis of the receptive language of a group of English-speaking WS
      individuals on a standardized morphosyntactic test. We then present an
      experimental study of expressive language that examines grammatical gender
      assignment in French-speaking WS patients. Despite a Verbal Mental Age selected
      to be higher than the chronological age of the young control group, these people
      with WS continue even in adulthood to show clear-cut deficits in their production
      of an aspect of morphosyntax that normal children acquire effortlessly very
      early. The results of the 2 studies, one focusing on receptive language and the
      other on expressive language, challenge the notion that comprehension and use of
      morphosyntactic rules in WS individuals are intact. The Within-domain
      dissociations regarding the use of grammatical gender assignment across several
      sentence clements and their difficulties in understanding embedded sentences-two
      quintessentially linguistic skills-suggest that we must rethink the notion of
      spared, modular, language capacities in Williams syndrome. We conclude that WS
      language follows a different path to normal acquisition and may turn out to be
      more like second language learning.

PMID- 9180001
TI  - Inhibitory control as a contributor to conscience in childhood: from toddler to
      early school age.
AB  - In this article we report a longitudinal extension of previous findings about the
      critical role of temperamental inhibitory or effortful control as the contributor
      to developing conscience in young children. A comprehensive observational
      battery, highly internally consistent, was developed to measure inhibitory
      control in 83 children at early school age who had been followed since
      toddlerhood and had been assessed using similar batteries at toddler and
      preschool age. We again confirmed the findings of robust longitudinal stability
      of inhibitory or effortful control, now from toddler to early school age, the
      increase with age, and gender differences, with girls outperforming boys. We also
      reaffirmed strong links, both contemporaneous and in the longitudinal sense,
      between inhibitory control and multiple, diverse measures of children's
      conscience at early school age, including observations of moral conduct, moral
      cognition, and moral self. The findings are discussed in view of the increasingly
      appreciated importance of temperament for critical aspects of socialization.

PMID- 9180002
TI  - Subtypes of social withdrawal in early childhood: sociometric status and social
      cognitive differences across four years.
AB  - From a sample of 567 kindergartners observed during free play, 150 children were
      classified as socially withdrawn and followed over 4 years. A cluster analysis
      involving teacher ratings was used to identify subtypes of withdrawn children.
      Four clusters were identified, 3 fitting profiles found in the literature and
      labeled unsociable (n = 96), passive-anxious (n = 23), and active-isolate (n =
      19), and 1 typically not discussed, labeled sad/depressed (n = 12). Sociometric
      ratings indicated that unsociable children had elevated rates of sociometric
      neglect, active-isolates had higher than expected levels of rejection, and
      sad/depressed children had elevated rates of both neglect and rejection. Subtypes
      also differed in social information-processing patterns, with active-isolate
      children displaying the least component skills. The findings that some experience
      more difficulty than others might account for the ambiguity in extant studies
      regarding whether or not social withdrawal is a risk factor in psychosocial
      development, because withdrawal has most often been treated as a unitary
      construct in the past.

PMID- 9180003
TI  - The relations of regulation and emotionality to resiliency and competent social
      functioning in elementary school children.
AB  - The relations of regulation and emotionality to elementary school children's
      social functioning were examined. Teachers and peers reported on children's
      social functioning; 1 parent and teacher rated children on various measures of
      regulation, resiliency, and emotionality; and a behavioral index of regulation
      was obtained. The effects of individual differences in attentional regulation on
      social status and socially appropriate behavior were mediated by resiliency, and
      dispositional negative emotionality moderated the positive relation between
      attentional control and resiliency (with this path being stronger for children
      high in negative emotionality). The effects of behavioral regulation were not
      mediated by resiliency; however, the relation of behavioral regulation to
      socially appropriate behavior (but not social status) was moderated by negative
      emotionality, with effects being significant and higher for children high in
      negative emotionality.

PMID- 9180004
TI  - Mothers' social coaching, mother-child relationship style, and children's peer
      competence: is the medium the message?
AB  - Contributions of mothers' social coaching and responsive style to preschoolers'
      peer competence were evaluated in 2 studies. In Study 1, 43 mother-child dyads
      participated in 3 laboratory tasks; videotapes were coded for responsive
      interaction style in play, advice regarding videotaped peer dilemmas (coaching),
      and nonsocial teaching in a puzzle task. Coaching and style were largely
      independent and were correlated with measures of social competence. In Study 2 (n
      = 62), coaching and style uniquely predicted teacher ratings, but only style
      predicted peer acceptance. To investigate whether coaching mediated the effects
      of style and/or whether style moderated the effects of coaching, the samples were
      combined. No evidence was found for mediation, but coaching was a more powerful
      predictor of lower levels of boys' aggression when the mother-child relationship
      was less responsive. Discussion focuses on models of socialization that stress
      the interplay of general style and specific socialization practices in promoting
      social competence.

PMID- 9180005
TI  - Marital conflict and adolescent distress: the role of adolescent awareness.
AB  - The present longitudinal study (1989-1991) of seventh-grade adolescents (173
      boys, 197 girls; M age = 12.7 in 1989) living in the rural Midwest examined the
      influence of children's awareness of marital conflict and reported level of
      parental hostility on symptoms of adolescent distress. The theoretical model
      guiding the research indirectly linked marital conflict to adolescent perceptions
      of parents' hostility through the mediating effects of parents' and observers'
      report of hostility toward the adolescent and through adolescent awareness of the
      frequency of interparental conflict. Controlling for earlier levels of
      psychological distress, we hypothesized a direct path between adolescent report
      of parent hostility and adolescent maladjustment. Maximum likelihood estimation
      of the proposed model showed that marital conflict was significantly related to
      parents' and observers' reports of parent hostility toward the adolescent and to
      adolescent awareness of conflict frequency. Both parent hostility and adolescent
      awareness of the frequency of marital conflicts were significantly related to
      adolescent perceptions of parent hostility. When controlled for earlier distress,
      adolescent report of parent hostility significantly predicted the later
      internalizing and externalizing symptoms of these teenagers. The model predicted
      externalizing problems for boys but not girls. Otherwise, there were no gender
      differences in the postulated causal processes.

PMID- 9180006
TI  - The academic achievement of adolescents from immigrant families: the roles of
      family background, attitudes, and behavior.
AB  - The goal of this study was to determine the relative impact of family background,
      parental attitudes, peer support, and adolescents' own attitudes and behaviors on
      the academic achievement of students from immigrant families. Approximately 1,100
      adolescents with Latino, East Asian, Filipino, and European backgrounds reported
      on their own academic attitudes and behaviors as well as those of their parents
      and peers. In addition, students' course grades were obtained from their official
      school records. Results indicated that first and second generation students
      received higher grades in mathematics and English than their peers from native
      families. Only a small portion of their success could be attributed to their
      socioeconomic background; a more significant correlate of their achievement was a
      strong emphasis on education that was shared by the students, their parents, and
      their peers. These demographic and psychosocial factors were also important in
      understanding the variation in academic performance among the immigrant students
      themselves.

PMID- 9180007
TI  - Length of maternity leave and quality of mother-infant interactions.
AB  - The aim of this study was to assess the association between the length of
      maternity leave and the quality of mother-infant interactions; 198 employed
      mothers of 4-month-old infants were interviewed and videotaped in their homes
      during a feeding time. Hierarchical multiple regression analyses indicated a
      direct association between shorter length of leave and more negative affect and
      behavior in maternal interactions with their infants. Infant and mother
      stressor/protective variables added significantly in predicting the quality of
      the mother-infant relationship. There were also significant interaction effects
      between the length of leave and these variables. Mothers who either reported more
      depressive symptoms or who perceived their infant as having a more difficult
      temperament and who had shorter leaves, compared with mothers who had longer
      leaves, were observed to express less positive affect, sensitivity, and
      responsiveness in interactions with their infants. The public policy implications
      of the relation between length of maternity leave, maternal and infant individual
      differences, and the quality of mother-infant interactions are discussed.

PMID- 9180008
TI  - Role of myosin isoforms in smooth muscle function.

PMID- 9180009
TI  - C-terminal isoforms of the myosin heavy chain and smooth muscle function.
AB  - Two myosin heavy chain isoforms expressed in smooth muscle, SM1 (204 kDa) and SM2
      (200 kDa), are derived from alternate splicing that results in different amino
      acid sequences at their non-helical C-terminal tail regions. These isoforms are
      developmentally regulated and differentially expressed in various smooth muscle
      tissues. The functional role of myosin isoforms differing at the C-terminal tail
      has been investigated both in vitro and in vivo. Removal of the C-terminal tail
      of SM1 by chymotrypsin activates the ATPase of myosin at low Mg2+ but does not
      change the maximum activity. Addition of peptides, mimicking C-terminal tail
      regions specific to the SM1 and SM2 isoforms, to permeabilized taenia coli smooth
      muscle fibers inhibits maximum shortening velocity (Vm) and decreases Ca2+
      sensitivity but has no effect on maximum force. The inhibition of Vm by the SM1
      peptide was not reversed on washout, whereas Vm inhibition by the SM2-peptide is
      reversible. We demonstrated that the SM1 peptide specifically bound to myosin at
      the subfragment 2-light meromyosin (S2-LMM) junction using crosslinking and
      immunomicroscopy. Modification at this site could have a direct effect on
      crossbridge function. The relation between C-terminal myosin isoforms and
      contractile function in vivo was examined using estrogen administration to
      ovariectomized rats to increase the relative expression of the SM1 C-terminal
      isoform in uterine smooth muscle. This increase in SM1 was significantly
      correlated with an increase in Vm. In contrast, the high ATPase N-terminal
      isoform was decreased by administration of estrogen to ovariectomized rats. Thus,
      changes in C-terminal isoform distribution appear to affect contractile function
      in vivo. We propose a mechanism whereby the interactions between the C-terminal
      tail of one myosin molecule and the S2-LMM region of another in the thick
      filament can modulate contractility in an isoform specific manner. Further work
      is needed to unequivocally identify the function of smooth muscle myosin
      isoforms. However, our evidence suggests that the C-terminal heavy chain isoforms
      may be important modulators of smooth muscle contractility.

PMID- 9180010
TI  - Myosin heavy chain isoforms in smooth muscle.
AB  - In recent years, significant progress has been made toward understanding smooth
      muscle myosin heavy chain (SMHC) structure. Molecular cloning analysis has
      identified four different MHC isoforms. They are products of a single gene and
      result from alternative mRNA splicing. In addition, two non-muscle MHC isoforms
      are also expressed in smooth muscle cells. Studies show that SMHC expression is
      highly tissue specific and does not appear in cardiac or skeletal muscle cells.
      Each smooth muscle tissue is characterized by a specific pattern of MHC isoform
      expression that changes during development and disease. This review essentially
      focuses on SMHC isoforms and their expression in mammals.

PMID- 9180011
TI  - Arterial muscle myosin heavy chains and light chains in spontaneous hypertension.
AB  - Increased maximum velocity of shortening (Vmax), increased shortening ability
      (delta Lmax) and decreased relaxation rate have been reported for arterial smooth
      muscle from 16- to 18-week-old spontaneously, hypertensive rats (SHR) compared
      with age-matched normotensive Wistar-Kyoto rats (WKY). Vmax is dependent on
      actomyosin ATPase activity, and this activity is in turn dependent on the level
      of phosphorylation of the 20-kDa myosin light chain (MLC20) normally a function
      of calcium concentration. In this article, methods are described and data are
      presented from studies addressing possible intracellular regulatory mechanisms
      that might lead to the altered contractility of the SHR arterial muscle. In one
      study, myofibrillar protein was extracted from 16- to 18-week-old SHR and WKY
      caudal arterial muscle. The Mg(2+)-activated ATPase activity was measured under
      conditions where the Ca2+ concentration was controlled. In another study, the
      amount of myosin present and relative proportions of the myosin heavy chain (MHC)
      isoforms were determined by quantitative SDS-PAGE using heavy molecular weight
      standards and bovine serum albumin as the standard for concentration. In a third
      study, MLC20 phosphorylation levels in electrically stimulated arterial muscle
      were determined by urea glycerol gel electrophoresis and Western blot analyses.
      The SHR (n = 6) myofibrillar ATPase liberated 0.011 +/- 0.003 mumol Pi/mg
      myosin/min, which was significantly more than the 0.006 +/- 0.001 mumol Pi/mg
      myosin/min liberated by the WKY (n = 4) myofibrillar ATPase (P < 0.05).
      Consistent with the increased ATPase activity, phosphorylation of MLC20 was
      increased by 2.8 times as much in the SHR compared with the WKY electrically
      stimulated arterial muscle. However, there was no difference in MHC isoform
      pattern in the SHR compared with the WKY arterial muscle in contrast to the
      findings of at least one other laboratory. This discrepancy is discussed. The
      data reviewed in this article lead to the conclusions that an increased actin
      activated myosin ATPase activity and MLC20 phosphorylation are likely responsible
      for the increased velocity of shortening previously reported in SHR arterial
      muscle and the increased ATPase activity is not a function of an increased myosin
      content or of altered MHC isoform pattern in the SHR muscle.

PMID- 9180012
TI  - Myosin isoform heterogeneity in single smooth muscle cells.
AB  - We review the current understanding of the myosin heavy chain (MHC) isoforms and
      show that the mRNA levels of smooth muscle (SM)1 and SM2 mimic the expressed
      levels of SM1 and SM2 protein. The reverse transcriptase-polymerase chain
      reaction technique has been shown to be sufficiently sensitive to examine SM-MHC
      expression at the single cell level. Most single smooth muscle cells isolated
      from adult rabbit carotid express both SM1 and SM2. However, expression of these
      SM-MHC isoforms at the cellular level is nonuniform and highly variable. This
      work provides a foundation for future investigations as to the possible unique
      functional characteristics of the SM-MHC isoforms, SM1 and SM2. This methodology
      may also prove useful when used with mechanical studies to determine the
      physiological significance of the alternatively spliced myosin isoforms,
      including the SM-MHC-head and LC17 isoforms.

PMID- 9180013
TI  - Characterization of isoform diversity among smooth muscle and nonmuscle myosin
      heavy chains.
AB  - In the last decade, as a result of molecular cloning and the reverse
      transcriptase polymerase chain reaction, numerous isoforms of the contractile
      protein myosin have been discovered. What lags behind their discovery is
      knowledge of their functions. This review focuses on some of my recent work on
      the structure, function and regulation of isoforms of the heavy chain of
      vertebrate smooth muscle and nonmuscle myosin II. Reference to related work in
      the field is included where appropriate. The particular isoforms discussed are
      those that are generated by alternative splicing near the 5' end of the pre-mRNA,
      resulting in either an insertion or a deletion of a cassette of amino acids near
      the amino-terminus of the myosin heavy chain (MHC) protein. In both the smooth
      muscle and nonmuscle MHCs, this splicing occurs in the exact same region, which
      begins at amino acid 212 in the primary sequence. In the three-dimensional
      structure of the molecule, these inserts are located near the ATP-binding pocket
      in a region of the MHC that was not resolved in the crystal structure and
      therefore is believed to represent a flexible loop. In the smooth muscle MHC, the
      insertion of seven amino acids in this loop confers a higher enzymatic activity
      on the myosin. The potential mechanism by which this occurs and the significance
      to smooth muscle contractile diversity is discussed. In the nonmuscle MHC, the
      insert in this region is a different size and sequence of amino acids than that
      in the smooth muscle MHC. A serine residue (Ser-214) in the nonmuscle loop is
      phosphorylated by p34cdc2 kinase in Xenopus during meiotic maturation of oocytes
      to eggs and is dephosphorylated in interphase egg extracts that are equivalent to
      the interphase after fertilization of the egg. Thus, MHC-B phosphorylation by
      cdc2 kinase correlates with the cortical reorganization that occurs during
      meiosis, and dephosphorylation correlates with the cortical contraction that
      occurs at fertilization, which aids in pronuclear fusion. In summary, these
      inserts in the MHC molecule, in a flexible loop near the ATP-binding pocket,
      appear to be important in determining differences in function or regulation among
      myosin II isoforms.

PMID- 9180014
TI  - Myosin isoforms and functional diversity in vertebrate smooth muscle.
AB  - The expression of fast and slow myosin isoforms in individual cells is associated
      with differences in shortening velocities and power output in fully
      differentiated vertebrate striated muscle. This paradigm in which shortening
      velocity is determined by the myosin isoform (and load) is inappropriate for
      smooth muscle. Smooth muscle tissues express multiple myosin heavy and light
      chain isoforms, and it is not currently possible to separate and identify
      chemically distinct native myosin hexamers (i.e., isoforms). It is not known if
      different isoforms are localized in subpopulations of cells or in specific
      cellular domains nor whether they combine preferentially to form a small number
      of native myosin hexamer isoforms. Potentially, thick filaments are aggregates of
      many different combinations of heavy and light chain isoforms that may or may not
      exhibit different kinetics. Shortening velocities in smooth muscle are regulated
      by Ca(2+)-dependent crossbridge phosphorylation of the myosin regulatory light
      chains. Much of the observed diversity in power output in smooth muscle may be
      attributed to regulatory mechanisms modulating crossbridge cycling rates rather
      than contractile protein isoform expression.

PMID- 9180015
TI  - Nongenetic variation, genetic-environmental interactions and altered gene
      expression. II. Disease, parasite and pollution effects.
AB  - The use of protein electrophoretic data for determining the relationships among
      species or populations is widespread and generally accepted. However, there are
      many confounding factors that may alter the results of an electrophoretic study
      and may possibly allow erroneous conclusions to be drawn in taxonomic, systematic
      or population studies. Measured enzyme activities can also be affected
      significantly. Parasites, disease and pollution can affect levels of enzyme
      activity, and electrophoretic results can be affected both quantitatively and
      qualitatively. Blood serum is particularly vulnerable to variation to variation
      due to disease, pollution or parasites because damaged tissues may release tissue
      specific enzymes into the bloodstream. Capture, handling, chemical treatments,
      bacteria, natural toxins and consumed food may also contribute to variation.
      Potential pollution impacts at specimen collection sites should be investigated,
      and study organisms should be inspected and/or treated for detection and
      elimination of parasites and disease.

PMID- 9180016
TI  - Plasma vitellogenin levels during the annual reproductive cycle of the female
      rainbow trout (Oncorhynchus mykiss): establishment and validation of an ELISA.
AB  - Rainbow trout, Oncorhynchus mykiss, vitellogenin (Vtg) was purified from plasma
      of E2-treated male by direct anion exchange chromatography and some of its
      biochemical characteristics were studied. Our results demonstrated that, under
      SDS-PAGE conditions, rainbow trout Vtg was composed of two molecular forms of 390
      and 176 kDa representing, respectively, the dimeric form and the monomeric from
      of the molecule. The purified Vtg was used to raise a polyclonal antibody for Vtg
      (anti-Vtg). Using this anti-Vtg, a competitive enzyme-linked immunosorbent assay
      (ELISA) was developed for the quantification of rainbow trout Vtg. The practical
      sensitivity range of this ELISA was 20-320 ng/ml (80-20% of binding) and the
      detection limit was 9 ng/ml. The intra- and the inter-assay coefficients of
      variation (at 50% of binding) were estimated at 1.8% (n = 10) and 3.9% (n = 13),
      respectively. This ELISA was validated by detecting changes in Vtg levels in
      rainbow trout at different physiological stages, as well as in 2-year-old female
      rainbow trout throughout the reproductive cycle.

PMID- 9180017
TI  - The mitochondrial membrane permeability transition induced by inorganic phosphate
      or inorganic arsenate. A comparative study.
AB  - The membrane permeability transition (MPT) induced by Ca2+ and Pi or Asi was
      studied in rat kidney mitochondria. Membrane potential, Ca2+ transport and
      swelling were used to monitor the MPT. Asi promoted a faster and more extensive
      collapse of membrane potential, Ca2+ release and swelling than Pi. The MPT
      induced by Pi was fully blocked by Mg(2+)+ADP, spermine+ADP, Mg(2+)+ cyclosporin
      A (CSA), and ADP+CSA. In contrast, the MPT induced by Asi was only prevented,
      although not completely, by CSA+Mg2+ or ADP+CSA. Asi, but not Pi, was able to
      cause collapse of membrane potential in the presence of Sr2+.
      Carboxyatractyloside (CAT) produced collapse of membrane potential at a lower
      concentration in the presence of Asi+Ca(2+)+ADP than with Pi+Ca(2+)+ADP. The
      addition of Pi+Ca2+ to [14C]-ADP loaded mitochondria brought about a greater ADP
      release than Asi+Ca2+. The ADP release was CAT-sensitive with Pi but it was only
      partially blocked by Asi. The diminution of external pH did not inhibit the MPT
      induced by Pi or Asi. The results of this study suggest that the adenine
      nucleotide translocase does not have an essential role in the MPT induced by
      Asi+Ca2+.

PMID- 9180018
TI  - Amino-terminal oxygen-binding functional unit of the Rapana thomasiana grosse
      (gastropod) hemocyanin: carbohydrate content, monosaccharide composition and
      amino acid sequence studies.
AB  - The amino-terminal oxygen-binding unit Rta of the Rapana thomasiana hemocyanin is
      a glycoprotein with a carbohydrate content of 4.8% (w/w). Sugar analysis revealed
      as monosaccharide constituents xylose, fucose, 3-O-methylgalactose, mannose,
      galactose, N-acetylgalactosamine and N-acetylglucosamine residues. On subtracting
      the carbohydrate contribution from the molecular mass of 49,698 Da, determined by
      laser desorption mass spectrometry for Rta, an M(r) value of 47,318 Da was
      determined for the polypeptide part of the functional unit. The Rapana hemocyanin
      oxygen-binding unit Rta contains 400 residues in a single polypeptide chain. The
      nearly complete amino acid sequence (about 90%) is determined. This is the first
      report on a sequence of a marine gastropod oxygen-binding unit and also on a
      molluscan hemocyanin amino-terminal unit. Comparison of the Rta sequence with
      those of other molluscan hemocyanin units, localized in the C-terminus or in the
      middle of the respective multidomain polypeptide chains, revealed 42-46% homology
      (52-55%, including isofunctional residues). Probably, all molluscan oxygen
      binding units evolved from a common ancestral gene.

PMID- 9180019
TI  - Comparison of age-related differences in expression of phospholipid hydroperoxide
      glutathione peroxidase mRNA and activity in various tissues of pigs.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPX) is the second
      identified Se-dependent intracellular glutathione peroxidase (PHGPX) that reduces
      phospholipid hydroperoxides. The objective of this study was to determine the
      developmental regulation of PHGPX expression in tissues of neonatal, weanling and
      finishing pigs (Sus scrofa) compared with the expression of the classic Se
      dependent cellular glutathione peroxidase (GPX) and the Se-independent enzyme,
      glutathione S-transferase (GST). Eight different tissues were collected from Se
      adequate male pigs aged 1, 28 and 180 days, and supernatant of the tissue
      homogenate was assayed for PHGPX, GPX and GST activities by using
      phosphatidylcholine hydroperoxide, hydrogen peroxide and 1-chloro-2,4
      dinitrobenzene as substrate, respectively. Total RNA was isolated from four
      tissues and assayed for PHGPX mRNA expression. Both mRNA and activity expression
      of PHGPX in most assayed tissues was increased as pigs became older (P < 0.05),
      but increases in PHGPX mRNA levels between ages did not fully account for all
      changes in activity. Expression of GPX activity was increased more than that of
      PHGPX between day 1 and day 28 (P < 0.0001). Expression of GST activity in
      various tissues was also affected by age (P < 0.01) but lacked a consistent
      relationship with the changes in GPX and PHGPX activity. Tissue-specific patterns
      of developmental expression of these enzymes may be related to the susceptibility
      of organs to pro-oxidant injuries. In conclusion, expression of PHGPX mRNA and
      activity in various tissues of pigs is developmentally increased over ages, and
      the pattern is somewhat different from that of GPX.

PMID- 9180020
TI  - Monocrotaline metabolism and distribution in Fisher 344 and Sprague-Dawley rats.
AB  - The metabolism and distribution of 14C-monocrotaline in Fisher 344 (F344) rats
      was compared with that in Sprague-Dawley (SD) rats. In vitro microsomal
      preparations, in situ isolated perfused livers and in vivo excretion and
      distribution studies were used to discern any differences between these two
      strains. These strains have previously been shown to differ in their
      susceptibility to monocrotaline-induced pulmonary hypertension. Hepatic phase I
      metabolism appears to be similar in both strains with N-oxidation and
      dehydrogenation to the reactive pyrroles as the major pathways. During the liver
      perfusions, SD rats generated more monocrotalic acid than F344 rats, but the
      microsome and excretion studies demonstrated no significant differences in the
      amount of monocrotalic acid. Monocrotalic acid is a stable byproducer of
      dehydromonocrotaline reacting with cellular nucleophiles and indicates the amount
      of monocrotaline dehydrogenation when carboxylesterase activity is negligible.
      These data suggest that the differences in strain susceptibility to pulmonary
      vascular toxicity is most likely due to differences in their response to the
      toxic metabolites.

PMID- 9180021
TI  - Kinetic characteristics of nucleoside mono-, di- and triphosphatase activities of
      the periplasmic 5'-nucleotidase of Escherichia coli.
AB  - Periplasmic 5'-nucleotidase from Escherichia coli, in addition to the
      monophosphoesterase activity has a diphosphohydrolase activity, acting on
      nucleoside di- and triphosphates. We proposed that the monophosphoesterase and
      diphosphohydrolase activities have their own active site. This proposal is based
      on the different types of bonds being broken. Chemical modification with
      selective group reagents did not show differences in the essentiality of some
      residues, like histidyl, carboxyl and arginyl groups, of these two hydrolytic
      activities. While kinetic approaches employing the competition plot and
      unidirectional substrate inhibition point to that diphosphohydrolase activity
      (ATPase-ADPase) do not share the same active site with monophosphoesterase
      activity. Western blotting developed with polyclonal anti-placental apyrase
      antibody revealed a single protein in the periplasmic fraction of 66.5 kDa
      similar to the Mr of the purified enzyme by isoelectrofocusing.

PMID- 9180024
TI  - Fractures at the base of the skull in gunshots to the head.
AB  - The distribution of fractures at the base of the skull was investigated in 147
      victims with lethal head shot wounds caused by handguns or small calibre low
      velocity rifles. In individuals without an impact of the projectile at the base
      of the skull, bullets lodged in the head were found up to a calibre of 7.65 mm
      (pistol) or .38 special (revolver), respectively. In cases with a trajectory
      through the cranial fossae positive results were obtained up to 9 mm (pistol) or
      even .45 (revolver). Fractures in anterior parts of the base of the skull were a
      rather frequent finding (82% of the cases) and could also be observed in victims
      shot by low energy guns. Fracture lines in particular in all cranial fossae,
      however, indicate a comparatively high energy missile and were found in victims
      without a direct impact of the bullet at the base of the skull after the use of
      guns with a calibre of at least 7.65 mm. Severe fractures leading to a hinge-like
      mobility of the base of the skull point also to projectiles of rather high
      energy. On the other hand, such fractures were also found in a victim with a
      contact shot by a .22 rifle. Therefore, it must be emphasized that individual
      factors such as the constitution of the base of the skull, the path of the
      bullet, technical parameters of the gun and ammunition used are of great
      importance if conclusions are to be drawn on an unknown gun by evaluation of
      fractures at the base of the skull.

PMID- 9180022
TI  - Effects of urea on M4-lactate dehydrogenase from elasmobranchs and urea
      accumulating Australian desert frogs.
AB  - We measured the effect of urea on M4-lactate dehydrogenase (M4-LDH) from
      elasmobranchs and Australian desert frogs (urea accumulators) and from two
      animals that do not accumulate urea, the axolotl and the rabbit. An analysis of
      the effect of urea on the Kd(NADH), V, V/K(m(prr)) and V/K(m(NADH)) shows that in
      all cases the major effect of urea was on the binding of pyruvate, which fits
      with data in the literature that show that urea acts as a competitive inhibitor
      of LDH. The characteristics of the elasmobranch enzymes are consistent with a
      proposed adaptation model, but the situation for the enzymes from the aestivating
      frogs is equivocal. Urea (400 mM) had less effect on the K(m(prr)) of M4-LDH from
      the urea accumulators than it did on the non-accumulators, suggesting a general
      adaptation and that the enzyme produced by the aestivating frogs (urea
      accumulators) is kinetically different from that of non-aestivating frogs (non
      accumulators). A new approach is used to characterize the overall pattern of
      adaptation to urea. The pattern is similar in an enzyme from an elasmobranch and
      an aestivating frog despite the temporary presence of urea in the latter and the
      phylogenetic difference between these animals.

PMID- 9180025
TI  - Spanish population data on seven loci: D1S80, D17S5, HUMTH01, HUMVWA, ACTBP2,
      D21S11 and HLA-DQA1.
AB  - Blood samples from 120 Spanish Caucasian individuals were amplified and typed by
      electrophoresis at six loci, and by reverse dot-blot hybridization at one locus.
      Results demonstrate the assumption of independence within and between the seven
      loci analyzed. Therefore, a Spanish population database has been established and
      statistical analysis shows that a high degree of discrimination can be obtained
      when all seven (or fewer) loci are used to characterize forensic biological
      evidence.

PMID- 9180026
TI  - Meprobamate overdosage: a continuing problem. Sensitive GC-MS quantitation after
      solid phase extraction in 19 fatal cases.
AB  - We describe a simple method for the urinary identification and blood quantitation
      of meprobamate suitable for any toxicological laboratory. After urinary screening
      using GC-MS technology, quantitation is performed by GC-MS in the selected-ion
      monitoring mode. Isolation of the drug is achieved by solid phase extraction on a
      C-18 cartridge. A specific elution is obtained by three volumes of
      acetone:triethylamine (99:1 v/v). Lidocaine is used as internal standard. RSDs
      (%) of the within-day and between-day precision studies are always less than 7.2
      on the entire range of calibration. Linearity is inspected using an analysis of
      variance ANOVA. Homogeneity of the variances is tested using Hartley's test.
      Weighted linear regression is then computed. Limits of detection and
      quantification are given by an analysis of the blanks. The present method was
      applied in our laboratory over a period of 1 year. Meprobamate appeared as a drug
      which still has a significant frequency (5.5%) and is the most frequently
      involved in fatal pharmaceutical overdoses (15.3%). Post mortem concentrations
      ranged from 41 to 397 mg/l (mean = 182) and are compared to those of the
      literature.

PMID- 9180027
TI  - Estimation of stature from stride length while walking fast.
AB  - Estimation of stature from various foot and shoe measurements with the help of
      statistical methods is well known. However, very little work has been reported on
      stature estimation from stride length. As the stride length may vary in different
      walking speeds, in the present paper, stride length of individuals were measured
      while walking fast on smooth substrate has been compared with the stride length
      in the normal pattern of walking. Although the formulae derived are different for
      faster pace, the range of error in estimation of stature remains almost the same.

PMID- 9180028
TI  - Subtyping of D20S85 STR alleles by single-strand conformation polymorphism (SSCP)
      analysis.
AB  - During a population study of STR locus D20S85, we discovered two types of
      sequence variations by direct sequencing of the alleles: two transitions each of
      G to A and A to G occur in the 5' flanking region in the individuals possessing
      allele 6 and some of those possessing allele 7 [1]. Using single-strand
      conformation polymorphism (SSCP) analysis, we were able to distinguish two
      subtypes of allele 7 from each other. This analysis method enables rapid
      screening for STR alleles of the same length with different sequences, and should
      find application to other complex STR loci because of the practical advantage of
      simplicity in comparison to sequencing.

PMID- 9180029
TI  - Theft behaviour and its consequences among kleptomaniacs and shoplifters--a
      comparative study.
AB  - This study is based on interviews with 37 persons fulfilling the DSM-IV criteria
      for kleptomania recruited through newspaper advertisements, and on 50 shoplifters
      interviewed directly after apprehension. Our hypothesis was that there are no
      absolute borders between 'pure' kleptomania according to DSM-IV and other forms
      of shoplifting. When asked about the latest case of shoplifting, one fifth of the
      shoplifters reported not having stolen the item for personal use and had later
      discarded it. A quarter of the kleptomaniacs reported ambivalence when asked if
      they needed the item in question. The degree of reported impulsivity and a
      feeling of not being oneself at the time of the theft was the same in the two
      groups. The two groups also estimated their degree of impulsivity, planning,
      thrill, relief, vengeance, need, pleasure on a Visual Analogue Scale (VAS) as
      well as the degree of psychiatric imbalance on the latest theft occasion. These
      estimates showed that there were no differences between the groups concerning the
      degree of planning, psychological imbalance and the need for the stolen item in
      question. The kleptomaniacs rated a feeling of inner tension before the theft
      higher than the shoplifters. The same was true concerning a feeling of relief
      during the theft and impulsivity. However, the shoplifters also rated high on all
      these items. Altogether, these findings support our hypothesis that many
      shoplifters, even if they do not fulfill all DSM criteria for kleptomania, may
      constitute a significant medical problem and should be offered support and
      treatment. Anti-depressants as well as the educational programmes developed by
      the Shoplifters Alternatives may be effective not only in cases of kleptomania
      but also for more unselected groups of non-professional shoplifters.

PMID- 9180030
TI  - A dedicated internal standard in fragment length analysis of hyperpolymorphic
      short tandem repeats.
AB  - Some of the most polymorphic short tandem repeats (STRs) have alleles differing
      in size by as little as one basepair. Since sizing precision with commercially
      available internal standards ordinarily does not allow safe discrimination at
      this level, typing is accomplished through comparisons with allelic ladders run
      on each gel. Here we introduce the use of optimally spaced sequenced alleles as a
      dedicated internal standard for measurement and typing of hyperpolymorphic STRs.
      We have constructed such a dedicated internal standard for HUMACTBP2 ([1]; Moos
      and Gallwitz, EMBO I., 5 (1983) 757-761) typing, including 25 sequenced, ROX
      labelled HUMACTBP2 alleles spanning the size range for alleles at this locus (233
      333 basepairs (bp)). Comparisons of inter-gel runs of selected alleles with this
      dedicated standard and the commercial GS500 internal standard demonstrate that
      only the presently described internal standard is suited for direct typing based
      on fragment length measurements only. Obvious advantages of this typing procedure
      are that fragment measurements are precise and in accordance with sequenced
      lengths, and that the typing procedure via an external allelic ladder is avoided.
      Sequences of the alleles used in the internal standard as well as of selected
      alleles for allelic ladders in two other hyperpolymorphic AAAG-repeat STRs,
      D11S554 (Phromchotikul et al., Hum. Mol. Genet., 3 (1991) 21) and HUMAPOA11
      (Kimpton et al., PCR Methods Appl., 3 (1993) 13-22) are also presented. To allow
      fragment length analysis of these two STRs, five D11S554 alleles, spanning from
      176 to 225 basepairs, were added to the dedicated internal standard. Performing
      similar comparisons as for HUMACTBP2, it is demonstrated that even if sizing
      accuracy is not as good as with HUMACTBP2, typing based on measured fragment size
      only may be achieved with both other STRs as well. Selecting different colours
      for the three STRs, triplex electrophoretic runs were performed of a Norwegian
      population database of 300 unrelated individuals. The probability that two
      unrelated individuals have the same type in all three STRs is 5 x 10(-7), and the
      combined paternity exclusion power 99.77%, indicating that this STR selection may
      represent a good choice for forensic genetic casework.

PMID- 9180031
TI  - Spatial distribution of dihydropyridine receptors in the plasma membrane of
      guinea pig cardiac myocytes investigated by correlative confocal microscopy and
      label-fracture electron microscopy.
AB  - Excitation-contraction coupling in cardiac muscle is thought to depend
      fundamentally on the spatial organization of sarcolemmal dihydropyridine
      receptors (L-type calcium channels) in relation to ryanodine receptors (calcium
      release channels of the sarcoplasmic reticulum). In the present study, we have
      investigated the distribution of dihydropyridine receptors in the guinea pig
      myocyte plasma membrane by correlative immunoconfocal microscopy and label
      fracture electron microscopy. Label-fracture, a method in freeze-fracture
      cytochemistry, permits immunogold localization of cell surface proteins in en
      face membrane views. Taken together, results from confocal microscopy and label
      fracture replicas suggest that, in the peripheral plasma membrane, calcium
      channels are organized predominantly in the form of clusters. Confocal microscopy
      also suggests a similar organization in the transverse tubules. It is
      hypothesized that these clusters may lie adjacent to junctional sarcoplasmic
      reticulum, permitting the close coupling of influx of calcium through plasma
      membrane calcium channels to trigger release of calcium from the intracellular
      stores, as part of the mechanism of calcium-induced calcium release.

PMID- 9180032
TI  - High-resolution immuno-scanning electron microscopy using a non-coating method:
      study of herpes simplex virus glycoproteins on the surface of virus particles and
      infected cells.
AB  - The expression of two glycoproteins, i.e. glycoprotein C (gC) and glycoprotein D
      (gD), of herpes simplex virus type 1 (HSV-1) on the surface of extracellular
      particles of this virus was examined by immuno-scanning electron microscopy.
      Scanning electron microscopy specimens of infected cells immuno-labelled against
      the glycoproteins with colloidal gold particles were prepared by a conventional
      coating and a non-coating method. Surface ultrastructure of infected cells and
      gold particles were observed more clearly with specimens prepared by the non
      coating method. The appearance of virus particles in association with
      glycoprotein expression on these particles and on the surface of infected cells
      was then studied. Progeny virus particles began to appear 6 h after infection,
      increased in number as the infection proceeded, and covered most of the cell
      surface by 16 h. Six to 24 h after the infection, the labelling density for each
      glycoprotein on virus particles remained constant. The labelling density for gD
      was always higher than that for gC. The patch-like distribution of gold-labelling
      against gD was often detected on infected cell monolayers at the exponential and
      late stage of one cycle of virus growth. The labelling density for gD on virus
      particles was the highest on these produced in Vero and L-929 cells, moderate in
      MRC-5, BHK-21 and FL cells, and the lowest in HEp-2 cells.

PMID- 9180033
TI  - Mitochondrial damage by a new antitumour agent furanonaphthoquinone derivative in
      human cervical cancer HeLa cells.
AB  - The intracellular ultrastructural changes induced by the new antitumour agent 2
      methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) were investigated in human cervical
      cancer HeLa cells in comparison with normal cervix cells. The normal cells were
      isolated from cervixes surgically resected from myoma patients and were keratin
      positive. FNQ3 at 3-5 micrograms ml-1 selectively damaged the HeLa cell
      mitochondria followed by rough-surfaced endoplasmic reticulum resulting in cell
      death. In contrast, normal cells remained unaffected at that concentration but
      were damaged by 20 micrograms ml-1 FNQ3. The FNQ3-induced tumour cell toxicity
      was inhibited 52% and 36% by trolox and a water-soluble fraction of the
      antioxidative substance AOB, respectively. The results indicated that FNQ3 is
      selectively toxic to HeLa cells at approximately eight times that of normal cells
      in terms of mitochondrial alteration and free radical formation.

PMID- 9180034
TI  - High-resolution electron microscopy of crystal contact in the demineralized
      dentine.
AB  - The mechanism of the dimensional increase in demineralized dentine crystals was
      investigated using a high-resolution transmission electron microscope. Lattice
      fringes were observed even in the demineralized crystals. The characteristics of
      demineralized dentine crystals mainly consisted of a partial disappearance of
      their lattice fringes along their lateral surface. High-resolution transmission
      electron microscopy also revealed that an intricate association between partially
      demineralized crystals occurred at the interface where incoherent or coherent
      tilt boundary, the dislocation of lattice fringes appeared. The present findings
      suggest that the dimensional increase in carious dentine could be brought by a
      crystal fusion.

PMID- 9180035
TI  - Topographic comparison of subneural apparatuses at neuromuscular junctions in
      normal and dystrophic (mdx) mice: a scanning electron microscope study.
AB  - The differences in the morphodifferentiation of subneural apparatuses (SNAs) at
      neuromuscular junctions (NMJs) in the extensor digitorum longus muscle of normal
      and dystrophic (mdx) mice were examined by scanning electron microscopy. In
      normal mice, primitive shallow cup-like synaptic troughs present at birth had
      developed to anastomosing grooves containing both pit-like and slit-like
      junctional folds (JFs) during the 2nd postnatal week. At the 35th day, the SNAs
      had developed to almost the adult forms, consisting of labyrinthine synaptic
      grooves with exclusively slit-like JFs. In the mdx mice, the SNAs showed
      transformation similar to those in the normal mice until the 35th postnatal day.
      After this period, SNAs with a number of cup-like depressions occurred and
      increased in number. These morphological changes seemed to be found on
      regenerating muscle fibers after necrosis, probably indicating the remodelling of
      their NMJs.

PMID- 9180037
TI  - Why can't most people draw what they see?
AB  - The study presented a theoretical and empirical approach to the adult drawing
      process. Four possible sources of drawing inaccuracies were described:
      misperception of the object, inability to make good representational decisions,
      deficient motor skills, and misperception of the drawing. In four studies the
      degree to which the latter three sources contributed to drawing inaccuracies was
      assessed. The results suggest that (a) motor coordination is a very minimal
      source of drawing inaccuracies, (b) the artist's decision-making process is a
      relatively minor source of drawing inaccuracies, and (c) the artist's
      misperception of his or her work is not a source of drawing inaccuracies. These
      results suggest that the artist's misperception of the object is the major source
      of drawing errors.

PMID- 9180036
TI  - Selective attention in a reaching task: effect of normal aging and Alzheimer's
      disease.
AB  - This study examined the ability of young adults, older adults, and older adults
      suffering from Alzheimer's disease (AD) to perform a selective reaching task.
      Normal aging did not increase interference caused by distractors. In contrast,
      patients with AD showed massively increased effects of distractor interference.
      AD patients showed a high probability of making responses to distractor items.
      The proportion of these incorrect responses was related to the inability to use
      inhibitory processes, which increased with the severity of AD. Responses to
      distractors occurred despite the fact that patients could discriminate targets
      and distractors and knew that their responses to distractors were in error. These
      data suggest that AD patients are impaired in their ability to inhibit incorrect
      responses.

PMID- 9180038
TI  - Dual mechanisms of negative priming.
AB  - Three experiments examined whether negative priming is a dually determined effect
      produced by inhibitory mechanisms and by a memorial process. Younger adults
      (Experiment 1) and older adults (Experiments 1-3) were tested in procedures that
      varied the likelihood of inducing retrieval of the prior trial. This was done by
      making test-trial target decoding difficult (Experiments 1 & 2) or by making
      prior information useful on some nonnegative priming trials (Experiment 3).
      Younger adults demonstrated negative priming under retrieval and nonretrieval
      conditions, with patterns of performance indicating different sources of negative
      priming effects. Older adults showed negative priming only under retrieval
      inducing conditions, consistent with the view of deficient inhibitory mechanisms
      for older adults. The data suggest that contextual variables critically determine
      whether negative priming is largely due to inhibition or to episodic retrieval.

PMID- 9180039
TI  - Talker identification based on phonetic information.
AB  - Accounts of the identification of words and talkers commonly rely on different
      acoustic properties. To identify a word, a perceiver discards acoustic aspects of
      an utterance that are talker specific, forming an abstract representation of the
      linguistic message with which to probe a mental lexicon. To identify a talker, a
      perceiver discards acoustic aspects of an utterance specific to particular
      phonemes, creating a representation of voice quality with which to search for
      familiar talkers in long-term memory. In 3 experiments, sinewave replicas of
      natural speech sampled from 10 talkers eliminated natural voice quality while
      preserving idiosyncratic phonetic variation. Listeners identified the sinewave
      talkers without recourse to acoustic attributes of natural voice quality. This
      finding supports a revised description of speech perception in which the phonetic
      properties of utterances serve to identify both words and talkers.

PMID- 9180040
TI  - Peripheral stimulus localization by infants: attention, age, and individual
      differences in heart rate variability.
AB  - The effect of attention to a focal stimulus on 3- to 6-month-old infants'
      peripheral stimulus localization was examined. Fixation was engaged on a central
      visual stimulus, and a stimulus was presented in the periphery after discrete
      time intervals (0 to 12 s) or until changes in heart rate (HR) occurred.
      Peripheral stimulus localization occurred less frequently when a significant HR
      deceleration had occurred (sustained attention) than when HR had returned to its
      prestimulus level (attention termination). A signal detection analysis showed
      that response bias was altered by attention and that during inattention infants
      with high HR variability were more likely to shift fixation away from the central
      stimulus independently of the presence of the peripheral stimulus. These data
      suggest that infant attention affects decision processes for continuing focal
      stimulus fixation rather than peripheral stimulus discriminability.

PMID- 9180041
TI  - Direction of motion influences perceptual identification of ambiguous figures.
AB  - It is known that the perceived identity of an ambiguous figure can influence how
      that figure is perceived to move. In 6 experiments, the converse effect-the role
      of motion in the perceptual identification of ambiguous figures (e.g., N.
      Tinbergen's, 1951, goose-hawk)-was examined. In general, observers were biased to
      identify a moving ambiguous figure as that object whose face pointed in the
      direction of motion. Experiments 1-4 replicated this basic effect over induced,
      apparent, and smooth motion displays. Results from Experiment 5 show that longer
      interstimulus intervals led to smaller biases, with all bias disappearing around
      1,500 ms. In Experiment 6, direction of motion influenced perceptual
      identification even in the presence of conflicting shape information.

PMID- 9180042
TI  - Types and tokens in visual processing: a double dissociation between the
      attentional blink and repetition blindness.
AB  - In rapid serial visual presentation tasks, correct identification of a target
      triggers a deficit for reporting a 2nd target appearing within 500 ms: an
      attentional blink (AB). A different phenomenon, termed repetition blindness (RB),
      refers to a deficit for the 2nd of 2 stimuli that are identical. What is the
      relationship between these 2 deficits? The present study obtained a double
      dissociation between AB and RB. AB and RB followed different time courses
      (Experiments 1 and 4A), increased target-distractor discriminability alleviated
      AB but not RB (Experiments 2 and 4A), and enhanced episodic distinctiveness of
      the two targets eliminated RB but not AB (Experiments 3 and 4B). The implications
      of the double dissociation between AB and RB for theories of visual processing
      are discussed.

PMID- 9180043
TI  - Stimulus-target compatibility for reaching movements.
AB  - Reaction time, movement time, and initial direction of reaching movements toward
      a target in left or right hemispace were measured. In Experiment 1, the target of
      movement and hand had to be selected; movements toward the imperative stimulus
      were initiated faster than movements toward the alternate target, and ipsilateral
      reaches were initiated faster than contralateral reaches. In Experiment 2, the
      difference between ipsilateral and contralateral reaches disappeared when no
      selection of the hand had to occur. In Experiment 3, no target had to be
      selected, and only a stimulus-hand compatibility effect appeared. The results
      reveal different compatibility effects (stimulus-target, stimulus-hand, target
      hand), implying that participants exploit different correspondences, depending on
      the degrees of freedom of the action. The notion of compatibility effects
      relating to movement targets offers a new perspective on the negative Simon
      effect and it questions the general concept of response codes.

PMID- 9180044
TI  - The line-motion illusion: attention or impletion?
AB  - When a brief lateral cue precedes an instantaneously presented horizontal line,
      observers report a sensation of motion in the line propagating from the cued end
      toward the uncued end. This illusion has been described as a measure of the
      facilitatory effects of a visual attention gradient (O. Hikosaka, S. Miyauchi, &
      S. Shimojo, 1993a). Evidence in the present study favors, instead, an account in
      which the illusion is the result of an impletion process that fills in
      interpolated events after the cue and the line are linked as successive states of
      a single object in apparent motion.

PMID- 9180045
TI  - Perceiving musical stability: the effect of tonal structure, rhythm, and musical
      expertise.
AB  - The goal of this study was to investigate several factors that determine musical
      stability in unaccompanied tonal melodies. Following M. R. Jones's (1987) theory
      of dynamic attending, the author assumed that strongly accented tones act as
      stable melodic reference points. Three main results were observed: (a) tonal
      structure, rhythm, and melodic factors (i.e., pitch skips or change in melodic
      contour) all contributed to defining the stability experienced on the melodic
      tones; (b) a linear combination of 5 melodic and rhythmic features provided a
      good fit to the stability ratings; and (c) some of these features contributed
      differently, depending on the extent of musical expertise of the participants.
      The results are interpreted within C. L. Krumhansl's (1990) model of tonal
      perception and Jones's theory of dynamic attending.

PMID- 9180046
TI  - Phonology can help or hurt the perception of print.
AB  - Phonological manipulations affect performance in a letter search task that
      requires only a shallow level of processing. In Experiment 1, phonology reduced
      accuracy in the letter search task when a pseudohomophone (GAIM) contained a
      target letter ("i") that was missing in the spelling of its (nonpresented) sound
      alike base word (GAME). In Experiment 2, phonology increased accuracy in the
      letter search task when the target letter was present in both the spelling of the
      pseudohomophone and the spelling of its sound-alike base word ("m" in GAIM and
      GAME). In Experiment 3, we showed that the phonology-hurts effect of Experiment 1
      is not peculiar to nonword letter strings but generalizes to familiar words. In
      Experiment 4, we obtained a phonology-hurts effect on correct response times when
      stimuli were visible until participants responded (stimuli were not masked).

PMID- 9180047
TI  - Blindness to response-compatible stimuli.
AB  - This contribution is devoted to the question of whether action-control processes
      may be demonstrated to influence perception. This influence is predicted from a
      framework in which stimulus processing and action control are assumed to share
      common codes, thus possibly interfering with each other. In 5 experiments, a
      paradigm was used that required a motor action during the presentation of a
      stimulus. The participants were presented with masked right- or left-pointing
      arrows shortly before executing an already prepared left or right keypress
      response. We found that the identification probability of the arrow was reduced
      when the to-be-executed reaction was compatible with the presented arrow. For
      example, the perception of a right-pointing arrow was impaired when presented
      during the execution of a right response as compared with that of a left
      response. The theoretical implications of this finding as well as its relation to
      other, seemingly similar phenomena (repetition blindness, inhibition of return,
      psychological refractory period) are discussed.

PMID- 9180048
TI  - Lexical neighborhood effects in phonetic processing.
AB  - Previous research on spoken word recognition has demonstrated that identification
      of a phonetic segment is affected by the lexical status of the item in which the
      segment occurs. W. F. Ganong (1980) demonstrated that a category boundary shift
      occurs when the voiced end of 1 voice-onset time continuum is a word but the
      voiceless end of another series is a word; this is known as the "lexical effect."
      A series of studies was undertaken to examine how lexical neighborhood; in
      contrast to lexical status, might influence word perception. Pairs of nonword
      series were created in which the voiced end of 1 series had a higher frequency
      weighted neighborhood density, whereas the reverse was true for the other series.
      Lexical neighborhood was found to affect word recognition in much the same way as
      lexical status.

PMID- 9180049
TI  - Possible explanations for trajectory curvature in multijoint arm movements.
AB  - Although the straightness of hand paths is a widely accepted feature of human
      multijoint reaching movement, detailed examinations have revealed slight
      curvatures in some regions of the workspace. This observation raises the question
      of whether planned trajectories are straight or curved. If they are straight, 3
      possible factors can explain the observed curvatures: (a) imperfect control, (b)
      visual distortion, or (c) interaction between straight virtual trajectories and
      the dynamics of the arm. Participants instructed to generate straight movement
      paths produced movements much straighter than those generated spontaneously.
      Participants generated spontaneously curved trajectories in the frontoparallel
      plane, where visual distortion is not expected. Electromyograms suggested that
      participants generated straighter paths without an increase in arm stiffness.
      These findings argue against the 3 factors. It follows that planned trajectories
      are likely to be curved.

PMID- 9180050
TI  - Perceptual adjustment to highly compressed speech: effects of talker and rate
      changes.
AB  - This study investigated the perceptual adjustments that occur when listeners
      recognize highly compressed speech. In Experiment 1, adjustment was examined as a
      function of the amount of exposure to compressed speech by use of 2 different
      speakers and compression rates. The results demonstrated that adjustment takes
      place over a number of sentences, depending on the compression rate. Lower
      compression rates required less experience before full adjustment occurred. In
      Experiment 2, the impact of an abrupt change in talker characteristics was
      investigated; in Experiment 3, the impact of an abrupt change in compression rate
      was studied. The results of these 2 experiments indicated that sudden changes in
      talker characteristics or compression rate had little impact on the adjustment
      process. The findings are discussed with respect to the level of speech
      processing at which such adjustment might occur.

PMID- 9180051
TI  - Matrix-assisted laser desorption/ionization mass spectrometric peptide mapping of
      the neural cell adhesion protein neurolin purified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis or acidic precipitation.
AB  - Neurolin is a cell surface protein involved in the neural regeneration and
      neogenesis of the central nervous system of goldfish. Its theoretical molecular
      mass, based on the amino acid sequence translated from the cDNA, is 58 kDa, but
      in SDS-PAGE it shows an apparent MW of 86 kDa. Neurolin is stated to be a
      glycoprotein and it contains five potential N- and 96 potential O-glycosylation
      sites. The complete characterization of the primary structure and initial
      investigations on the postulated glycosylation of neurolin, immunopurified from
      goldfish brains, are described. The protein was either digested in situ in the
      sodium dodecyl sulfate polyacrylamide gel matrix or digested after
      trichloroacetic acid precipitation. Trypsin and endoprotease Glu-C were used as
      proteases and matrix-assisted laser desorption/ionization mass spectrometry was
      applied for direct peptide mapping analysis of the proteolytic mixtures. Various
      sample preparation techniques were performed and the mass spectra were recorded
      in both positive- and negative-ion modes.

PMID- 9180052
TI  - Determination of homovanillic acid and vanillylmandelic acid in neuroblastoma
      screening by stable isotope dilution GC-MS.
AB  - A method for the quantitative determination of homovanillic acid (HVA) and
      vanillylmandelic acid (VMA), two metabolites of catecholamines, is presented. The
      assay is based on gas chromatography/electron impact mass spectrometry. The
      preparation of 13C-labeled VMA from [13C6]vanillin is described. Together with
      purchased deuterated HVA the 13C-labeled VMA is used as an internal standard in
      stable isotope dilution GC/MS. The method involves elution from soaked filter
      papers, determination of creatinine content, extraction of HVA and VMA from
      eluted and urinary samples and derivatization to the di-and tri(trimethylsilyl)
      derivatives, respectively. The detection limits were found to be 4.0 pg for HVA
      and 0.8 pg for VMA. The method was applied to the routine determination of
      urinary HVA and VMA in a range from 5 to 100 ng HVA and VMA per microgram
      creatinine. The lower limits of pathological concentrations are set at 35 ng
      micrograms-1 creatinine for HVA and to 20 ng micrograms-1 creatinine for VMA,
      which are in close correlation with the values from other methods, but with the
      main advantage of reducing the amount of questionable or elevated results from
      6.7% (high-performance liquid chromatography (HPLC) alone) to 0.9% (HPLC and
      GC/MS).

PMID- 9180053
TI  - Different quantification approaches for the analysis of biological and
      environmental samples using inductively coupled plasma mass spectrometry.
AB  - For the analysis of biological and environmental materials by inductively coupled
      plasma mass spectrometry (ICP-MS), several quantification procedures can be used
      depending on the precision and accuracy required. Semi-quantitative methods based
      on the molar response curve were compared with conventional external calibration
      and standard additions for the analysis of waters and sewage sludges. For the
      analysis of biological materials, where higher quality data were required,
      isotope dilution analysis using enriched isotopes was applied. It was observed
      that the molar sensitivity for different elements in ICP-MS was a simple function
      of the mass of the isotopes measured after normalization for ionization
      efficiency which could be fitted to a third-order polynomial equation. Element
      ionization adjustments for the third-order polynomial, using the Saha equation,
      allowed the calculation of the plasma ionization temperature and electron
      density. For the determination of trace metals in waters and sewage sludges, the
      samples were spiked with different internal standards, ionization corrections
      were performed and the results obtained agreed with those obtained by external
      calibration and standard addition within a factor of 2 but, on average, the
      agreement was within 20%. The determination of molybdenum in biological reference
      materials was performed by isotope dilution analysis taking into account possible
      sources of error in the measurements by ICP-MS such as mass discrimination,
      detector dead time, isobaric interferences and random error propagation.

PMID- 9180054
TI  - Construal: overview, motivation, and some new evidence.
AB  - Is there underspecification in the syntactic phrase marker constructed during on
      line sentence analysis? According to the construal hypothesis (Frazier & Clifton,
      1996), a very limited amount and type of structural underspecification is
      available to the human sentence parsing mechanism. Here we present the basic
      definitions of construal, illustrating the theory with some already published
      evidence. We also discuss several new pieces of evidence, from our laboratory and
      elsewhere, that support the construal hypothesis. We end by raising the question
      of what kind of mechanism operates in the process of interpreting a nonprimary
      phrase (a phrase that receives an underspecified syntactic analysis), and
      conclude that it is not a process of competition between multiple activated
      possible analyses but instead is a process in which the sheer existence of
      ambiguity need not result in increased processing cost.

PMID- 9180055
TI  - Principles and practice of parenteral nutrition in the neonatal period.
AB  - In extremely preterm or critically ill infants, the parenteral route for
      maintaining nutritional integrity has to be relied upon before successful
      transition to the enteral route of feeding is achieved. Parenteral nutrition is
      now a fundamental part of neonatal intensive care. Fluid intake volumes vary from
      60-150 ml/kg/d, depending on maturity of the infant and environmental conditions
      influencing insensible water loss from the skin. Parenteral nitrogen requirements
      are 30-35 mmol/kg/d, equivalent to 3.0-3.5 mg/kg/d of amino acids. Hyperglycaemia
      during parenteral nutrition can be minimised by starting glucose infusion at a
      rate of 6-8 g/kg/d with progressive increase to 18-20 g/kg/d by 2-3 weeks after
      birth. Parenteral fat is introduced at 1 g/kg/d, gradually increasing to 3
      g/kg/d, given as a continuous infusion. An energy intake of 50 kcal/kg/d is
      adequate to match ongoing expenditure but an additional energy intake of 70
      kcal/kg/d is required to achieve optimal growth. Minerals and trace elements
      delivered with parenteral nutrition are calculated to meet in-utero accretion
      rates. Multivitamins available for parenteral use should also be included.
      Improved techniques for the preparation, administration and monitoring of
      parenteral nutrition have helped minimise catheter-related and metabolic
      complications. In neonatal intensive care units where appropriate medical,
      nursing, pharmacy and laboratory expertise are available, the potential benefits
      of parenteral nutrition outweigh its hazards. Nevertheless, early initiation of
      enteral feeding in small subnutritional quantities to supplement parenteral
      nutrition is of major importance to enhance the growth and development of the
      gastrointestinal tract.

PMID- 9180056
TI  - Ethical decision-making in newborn infants.
AB  - One ethical dilemma which neonatologists are faced with on a regular basis is
      selective non-treatment, that is, clinical decisions made after the birth of a
      liveborn infant to withhold or to withdraw treatment in certain circumstances.
      Although the outcome of extremely preterm of critically ill infants has
      significantly improved over the last decade, many are often left to die at birth
      by withholding resuscitation or neonatal intensive care. Criteria for initiating
      life-sustaining treatment must be developed with proper ethical considerations.
      There are other infants whose clinical course after initiation of intensive care
      will suggest that further curative efforts are futile or lack compensating
      benefit. Criteria for withdrawing life-sustaining treatment must also be
      developed, and palliative care measures defined. Clinical situations in which
      selective non-treatment is taking place in neonatal medicine are: (1) when death
      is considered to be inevitable whatever treatment is provided, (2) even when
      death is not inevitable, there is a significantly high risk of severe physical
      and mental disability should the infant survive, and (3) when survival with
      moderate disability is possible, but the infant is likely to experience ongoing
      pain and suffering, repeated hospitalisation and invasive treatment, and early
      death in childhood. The decision-making process of selective non-treatment should
      involve less medical paternalism and more informed parental involvement. The
      process is built on trust between the neonatal staff and parents, and requires
      time, information, honesty and empathy. Ethical issues must be approached with
      extreme responsibility, extraordinary sensitivity and heroic compassion.

PMID- 9180057
TI  - Design and methods of a population-based natural history study of cervical
      neoplasia in a rural province of Costa Rica: the Guanacaste Project.
AB  - This paper reports on the enrollment phase of a population-based natural history
      study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with
      consistently high rates of invasive cervical cancer. The main goals of the study
      are to investigate the role of human papillomavirus (HPV) infection and its co
      factors in the etiology of high-grade cervical neoplasia, and to evaluate new
      cervical cancer screening technologies. To begin, a random sample of censal
      segments was selected and enumeration of all resident women 18 years of age and
      over was conducted with the aid of outreach workers of the Costa Rican Ministry
      of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%)
      were interviewed after giving written informed consent. After the interview on
      cervical cancer risk factors was administered, a pelvic examination was performed
      on those women who reported previous sexual activity. The pelvic examination
      included a vaginal pH determination and collection of cervical cells for
      cytologic diagnosis using three different techniques. Additional cervical cells
      were collected for determination of the presence and amount of DNA from 16
      different types of HPV, and two photographic images of the cervix were taken and
      interpreted offsite by an expert colposcopist. Finally, blood samples were
      collected for immunologic and micronutrient assays. Women with any abnormal
      cytologic diagnosis or a positive Cervigram, as well as a sample of the whole
      group, were referred for colposcopy, and biopsies were taken when lesions were
      observed. The enrollment screening will serve as the basis for a prevalent case
      control study, and the members of the cohort free from serious disease will be
      followed actively, at intervals of no more than a year, to study the natural
      history of HPV infection and the origins of high-grade squamous intraepithelial
      lesions (HSIL). Details of the field operation are outlined, with particular
      reference to the realization of this kind of study in developing countries.
      Descriptive data on the prevalence of disease and exposure to various risk
      factors are also presented.

PMID- 9180059
TI  - Clinical manifestations of dengue hemorrhagic fever in Puerto Rico, 1990-1991.
      Puerto Rico Association of Epidemiologists.
AB  - The aim of the study reported here was to demonstrate that dengue hemorrhagic
      fever occurs in Puerto Rico, that it is underreported, and that this
      underreporting is due partly to underdiagnosis in hospitals. Surveillance for
      severe dengue identified 986 hospitalizations for suspected dengue in 1990-1991.
      At the time, on the basis of available clinical and laboratory data, the
      surveillance system routinely identified 20 DHF cases, including three with
      dengue shock syndrome (DSS). Our subsequent review of these 986 patients'
      hospital records identified 102 whose records supported a clinical diagnosis of
      DHF (88) or DSS (14). Of the 102, there were 57 with positive virologic or
      serologic results for dengue and that met the World Health Organization criteria
      for DHF (fever, hemorrhagic manifestations, thrombocytopenia, and excessive
      capillary permeability). This group of 57 patients had a mean age of 38 years,
      contained a preponderance of males (34, 59.3%), included eight cases of DSS, and
      involved two (3.5%) fatalities (in females 16 and 55 years old). Hemorrhagic
      manifestations were mild; hemoconcentration, hypoalbuminemia, and elevated
      aspartate and alanine aminotransferase (AST and ALT) levels were frequently
      encountered. The median duration of hospitalization was five days. The clinical
      description of these laboratory-positive DHF cases in Puerto Rico is consistent
      with previous descriptions of DHF in the medical literature; but the patients'
      age distribution is similar to the pattern typically found in the Americas (where
      all age groups tend to be affected), as opposed to Southeast Asia (where mostly
      younger children are affected). The number of DHF cases identified by our study
      was nearly three times that reported through the established surveillance system.
      Our findings indicate that recognition and reporting of DHF by local clinicians
      needs to be improved.

PMID- 9180060
TI  - Clinical implications of the "Multicenter Automatic Defibrillator Implantation
      Trial" (MADIT)
AB  - Efficacious therapy for chronic coronary patients, known to be at high risk of
      sudden arrhythmic death, has been a long-lasting challenge for cardiologists. The
      "Multicenter Automatic Defibrillator Implantation Trial" (MADIT) has demonstrated
      in a prospective, randomized trial that such patients achieve 54% better survival
      (p < or = 0.009) when treated with implantable defibrillators (ICDs) compared to
      conventional pharmaceutical therapy-primarily amiodarone. The identification of
      these patients is well-defined, and patients with previous myocardial infarction
      fitting the appropriate risk profile as defined by MADIT (ejection.fraction < or
      = 0.35), non-sustained ventricular tachycardia should seriously be considered for
      prophylactic ICD implantation.

PMID- 9180061
TI  - Power spectrum analysis of circadian oscillations of heart rate variability in
      patients with left ventricular dysfunction.
AB  - OBJECTIVES: The physiological significance of diurnal fluctuations in heart rate
      variability (HRV) has not been established to a full extent. The aim of our
      investigation was to assess a new method of power spectrum analysis of circadian
      oscillations in HRV in patients with left ventricular systolic and diastolic
      dysfunction. METHODS: Holter ECG monitoring and echocardiography were performed
      in 101 patients with coronary artery disease and arterial hypertension: 55
      patients with systolic left ventricular dysfunction (LVD) and 46 patients with
      diastolic LVD, and also in 32 subjects of the control group. The original method
      of HRV assessment was based on spectrum analysis of time series of consecutive 5
      minute measures of standard deviations of mean RR intervals. RESULTS: The study
      revealed oscillations of HRV with a periodicity of 12 hours and 80-120 minutes.
      Their amplitude was highest in the control group and lowest in patients with
      systolic LVD. CONCLUSIONS: Power spectrum analysis of circadian oscillations of
      heart rate variability reveals information about the character of LVD. Regular
      oscillations of time domain indices of HRV were observed in the patients with LVD
      and in the control group; their amplitude is highest in the control group and
      lowest in systolic LVD.

PMID- 9180062
TI  - Ambient air concentrations of fine (PM2.5) manganese in U.S. national parks and
      in California and Canadian cities: the possible impact of adding MMT to unleaded
      gasoline.
AB  - The October 1995 court decision allowing Ethyl Corporation to offer
      methylcyclopentadienyl manganese tricarbonyl (MMT) for sale to refiners for
      introduction into unleaded gasoline as an octane enhancer is likely to result in
      increased fine (PM2.5) manganese (Mn) concentrations in ambient air. Concern
      exists regarding possible health effects. In this paper, recent fine Mn
      concentrations in three monitoring networks and one U.S. Environmental Protection
      Agency (EPA) study of personal exposure are analyzed. One network consists mainly
      of rural sites in national parks in the United States, a second consists mainly
      of urban sites in California, and the third consists mainly of urban sites in
      Canada where MMT has been used for a number of years. During the late 1980s and
      early 1990s, mean ambient concentrations ranged from 1 ng/m3 in the mostly rural
      network to 3 ng/m3 in the mostly urban California network to 12 ng/m3 in the MMT
      impacted Canadian network. Several lines of evidence suggested that some of the
      fine Mn observed in the United States during the 1986-1992 period was contributed
      by automobiles using leaded gasoline, for which MMT was a registered fuel
      additive. However, the near-disappearance of leaded gasoline has resulted in a
      very small portion of fine Mn being attributed to automobiles in the years since
      1992. A source apportionment analysis suggested that crustal contributions to
      ambient fine Mn are on the order of 1-2 ng/m3 in both the United States and
      Canada.

PMID- 9180063
TI  - Screening of biofiltering material for VOC treatment.
AB  - Screening of biofiltering material for treatment of volatile organic compounds
      was performed by using a gas stream containing methyl ethyl ketone (MEK) as a
      target pollutant. Filtering media (FM) for screening were prepared by blending
      compost (such as pig and cow manure) and filling material (such as fern chips,
      wheat bran, and bagasse). Results show that a blend of pig manure/fern chips =
      9:1 (wt basis) was superior with respect to the stability of the pH and the water
      holding capacity of the FM and in the capacity for treating the target compound.
      Complete removal of the target compound was obtained at an organic loading of 100
      g per cubic meter of filtering media per hour. By using the screened FM for
      treating MEK and toluene, long-term stability (> 1,200 hours) and complete
      removal can be obtained at an organic loading of 50 g per cubic meter of FM per
      hour for either compound.

PMID- 9180064
TI  - Evaluation of the TEOM method for measurement of ambient particulate mass in
      urban areas.
AB  - Increased interest in the health effects of ambient particulate mass (PM) has
      focused attention on the evaluation of existing mass measurement methodologies
      and the definition of PM in ambient air. The Rupprecht and Patashnick Tapered
      Element Oscillating MicroBalance (TEOM) method for PM is compared with time
      integrated gravimetric (manual) PM methods in large urban areas during different
      seasons. Comparisons are conducted for both PM10 and PM2.5 concentrations. In
      urban areas, a substantial fraction of ambient PM can be semi-volatile material.
      A larger fraction of this component of PM10 may be lost from the TEOM-heated
      filter than the Federal Reference Method (FRM). The observed relationship between
      TEOM and FRM methods varied widely among sites and seasons. In East Coast urban
      areas during the summer, the methods were highly correlated with good agreement.
      In the winter, correlation was somewhat lower, with TEOM PM concentrations
      generally lower than the FRM. Rubidoux, CA, and two Mexican sites (Tlalnepantla
      and Merced) had the highest levels of PM10 and the largest difference between
      TEOM and manual methods. PM2.5 data from collocation of 24-hour manual samples
      with the TEOM are also presented. As most of the semi-volatile PM is in the fine
      fraction, differences between these methods are larger for PM2.5 than for PM10.

PMID- 9180065
TI  - Randomised controlled trial of graded exercise in patients with the chronic
      fatigue syndrome.
AB  - OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the
      chronic fatigue syndrome. DESIGN: Randomised controlled trial with control
      treatment crossover after the first follow up examination. SETTING: Chronic
      fatigue clinic in a general hospital department of psychiatry. SUBJECTS: 66
      patients with the chronic fatigue syndrome who had neither a psychiatric disorder
      nor appreciable sleep disturbance. INTERVENTIONS: Random allocation to 12 weeks
      of either graded aerobic exercise or flexibility exercises and relaxation
      therapy. Patients who completed the flexibility programme were invited to cross
      over to the exercise programme afterwards. MAIN OUTCOME MEASURE: The self rated
      clinical global impression change score, "very much better" or "much better"
      being considered as clinically important. RESULTS: Four patients receiving
      exercise and three receiving flexibility treatment dropped out before completion.
      15 of 29 patients rated themselves as better after completing exercise treatment
      compared with eight of 30 patients who completed flexibility treatment. Analysis
      by intention to treat gave similar results (17/33 v 9/33 patients better).
      Fatigue, functional capacity, and fitness were significantly better after
      exercise than after flexibility treatment. 12 of 22 patients who crossed over to
      exercise after flexibility treatment rated themselves as better after completing
      exercise treatment 32 of 47 patients rated themselves as better three months
      after completing supervised exercise treatment 35 of 47 patients rated themselves
      as better one year after completing supervised exercise treatment. CONCLUSION:
      These findings support the use of appropriately prescribed graded aerobic
      exercise in the management of patients with the chronic fatigue syndrome.

PMID- 9180066
TI  - Discontinuation of cervical spine immobilisation in unconscious patients with
      trauma in intensive care units--telephone survey of practice in south and west
      region.
AB  - OBJECTIVE: To study how the cervical spine is assessed before discontinuation of
      cervical spine immobilisation in unconscious trauma patients in intensive care
      units. DESIGN: Telephone interview of consultants responsible for adult intensive
      care units. SETTING: All 25 intensive care units in the South and West region
      that admit victims of major trauma. MAIN OUTCOME MEASURES: The clinical and
      radiological basis on which the decision is made to stop cervical spine
      immobilisation in unconscious patients with trauma. RESULTS: In 19 units cervical
      spine immobilisation was stopped in unconscious patients on the basis of
      radiology alone, and six units combined radiology with clinical examination after
      the patient had regained consciousness. Sixteen units relied on a normal lateral
      radiological view of the cervical spine alone, five required a normal lateral and
      anteroposterior view, and four required a normal lateral, anteroposterior, and
      open mouth peg view. CONCLUSIONS: There are inconsistencies in the clinical and
      radiological approach to assessing the cervical spine in unconscious patients
      with trauma before the removal of immobilisation precautions. There is an
      overreliance on the lateral cervical spine view alone, which has been shown to be
      insensitive in this setting.

PMID- 9180067
TI  - Alcohol consumption and cognitive performance in a random sample of Australian
      soldiers who served in the Second World War.
AB  - OBJECTIVE: To examine the association between the average daily alcohol intake of
      older men in 1982 and cognitive performance and brain atrophy nine years later.
      SUBJECTS: Random sample of 209 Australian men living in the community who were
      veterans of the second world war. Their mean age in 1982 was 64.3 years. MAIN
      OUTCOME MEASURES: 18 standard neuropsychological tests measuring a range of
      intellectual functions. Cortical, sylvian, and vermian atrophy on computed
      tomography. RESULTS: Compared with Australian men of the same age in previous
      studies these men had sustained a high rate of alcohol consumption into old age.
      However, there was no significant correlation, linear or non-linear, between
      alcohol consumption in 1982 and results in any of the neuropsychological tests in
      1991; neither was alcohol consumption associated with brain atrophy on computed
      tomography. CONCLUSION: No evidence was found that apparently persistent lifelong
      consumption of alcohol was related to the cognitive functioning of these men in
      old age.

PMID- 9180068
TI  - Short-term effects of ambient sulphur dioxide and particulate matter on mortality
      in 12 European cities: results from time series data from the APHEA project. Air
      Pollution and Health: a European Approach.
AB  - OBJECTIVES: To carry out a prospective combined quantitative analysis of the
      associations between all cause mortality and ambient particulate matter and
      sulphur dioxide. DESIGN: Analysis of time series data on daily number of deaths
      from all causes and concentrations of sulphur dioxide and particulate matter
      (measured as black smoke or particles smaller than 10 microns in diameter (PM10))
      and potential confounders. SETTING: 12 European cities in the APHEA project (Air
      Pollution and Health: a European Approach). MAIN OUTCOME MEASURE: Relative risk
      of death. RESULTS: In western European cities it was found that an increase of 50
      micrograms/m3 in sulphur dioxide or black smoke was associated with a 3% (95%
      confidence interval 2% to 4%) increase in daily mortality and the corresponding
      figure for PM10 was 2% (1% to 3%). In central eastern European cities the
      increase in mortality associated with a 50 micrograms/m3 change in sulphur
      dioxide was 0.8% (-0.1% to 2.4%) and in black smoke 0.6% (0.1% to 1.1%).
      Cumulative effects of prolonged (two to four days) exposure to air pollutants
      resulted in estimates comparable with the one day effects. The effects of both
      pollutants were stronger during the summer and were mutually independent.
      CONCLUSIONS: The internal consistency of the results in western European cities
      with wide differences in climate and environmental conditions suggest that these
      associations may be causal. The long term health impact of these effects is
      uncertain, but today's relatively low levels of sulphur dioxide and particles
      still have detectable short term effects on health and further reductions in air
      pollution are advisable.

PMID- 9180069
TI  - Structural insights into the evolution of an antibody combining site.
AB  - The crystal structures of a germline antibody Fab fragment and its complex with
      hapten have been solved at 2.1 A resolution. These structures are compared with
      the corresponding crystal structures of the affinity-matured antibody, 48G7,
      which has a 30,000 times higher affinity for hapten as a result of nine
      replacement somatic mutations. Significant changes in the configuration of the
      combining site occur upon binding of hapten to the germline antibody, whereas
      hapten binds to the mature antibody by a lock-and-key fit mechanism. The
      reorganization of the combining site that was nucleated by hapten binding is
      further optimized by somatic mutations that occur up to 15  from bound hapten.
      These results suggest that the binding potential of the primary antibody
      repertoire may be significantly expanded by the ability of germline antibodies to
      adopt more than one combining-site configuration, with both antigen binding and
      somatic mutation stabilizing the configuration with optimal hapten
      complementarity.

PMID- 9180070
TI  - A disk of scattered icy objects and the origin of Jupiter-family comets.
AB  - Orbital integrations carried out for 4 billion years produced a disk of scattered
      objects beyond the orbit of Neptune. Objects in this disk can be distinguished
      from Kuiper belt objects by a greater range of eccentricities and inclinations.
      This disk was formed in the simulations by encounters with Neptune during the
      early evolution of the outer solar system. After particles first encountered
      Neptune, the simulations show that about 1 percent of the particles survive in
      this disk for the age of the solar system. A disk currently containing as few as
      approximately 6 x 10(8) objects could supply all of the observed Jupiter-family
      comets. Two recently discovered objects, 1996 RQ20 and 1996 TL66, have orbital
      elements similar to those predicted for objects in this disk, suggesting that
      they are thus far the only members of this disk to be identified.

PMID- 9180075
TI  - Differential effects of cytolytic T cell subsets on intracellular infection.
AB  - In analyzing mechanisms of protection against intracellular infections, a series
      of human CD1-restricted T cell lines of two distinct phenotypes were derived.
      Both CD4(-)CD8(-) (double-negative) T cells and CD8(+) T cells efficiently lysed
      macrophages infected with Mycobacterium tuberculosis. The cytotoxicity of CD4(
      )CD8(-) T cells was mediated by Fas-FasL interaction and had no effect on the
      viability of the mycobacteria. The CD8(+) T cells lysed infected macrophages by a
      Fas-independent, granule-dependent mechanism that resulted in killing of
      bacteria. These data indicate that two phenotypically distinct subsets of human
      cytolytic T lymphocytes use different mechanisms to kill infected cells and
      contribute in different ways to host defense against intracellular infection.

PMID- 9180076
TI  - Multiple and ancient origins of the domestic dog.
AB  - Mitochondrial DNA control region sequences were analyzed from 162 wolves at 27
      localities worldwide and from 140 domestic dogs representing 67 breeds. Sequences
      from both dogs and wolves showed considerable diversity and supported the
      hypothesis that wolves were the ancestors of dogs. Most dog sequences belonged to
      a divergent monophyletic clade sharing no sequences with wolves. The sequence
      divergence within this clade suggested that dogs originated more than 100,000
      years before the present. Associations of dog haplotypes with other wolf lineages
      indicated episodes of admixture between wolves and dogs. Repeated genetic
      exchange between dog and wolf populations may have been an important source of
      variation for artificial selection.

PMID- 9180077
TI  - Elementary calcium-release units induced by inositol trisphosphate.
AB  - The extent to which inositol 1,4,5-trisphosphate (InsP3)-induced calcium signals
      are localized is a critical parameter for understanding the mechanism of effector
      activation. The spatial characteristics of InsP3-mediated calcium signals were
      determined by targeting a dextran-based calcium indicator to intracellular
      membranes through the in situ addition of a geranylgeranyl lipid group.
      Elementary calcium-release events observed with this indicator typically lasted
      less than 33 milliseconds, had diameters less than 2 micrometers, and were
      uncoupled from each other by the calcium buffer EGTA. Cellwide calcium transients
      are likely to result from synchronized triggering of such local release events,
      suggesting that calcium-dependent effector proteins could be selectively
      activated by localization near sites of local calcium release.

PMID- 9180078
TI  - Shared motor error for multiple eye movements.
AB  - Most natural actions are accomplished with a seamless combination of individual
      movements. Such coordination poses a problem: How does the motor system
      orchestrate multiple movements to produce a single goal-directed action? The
      results from current experiments suggest one possible solution. Oculomotor
      neurons in the superior colliculus of a primate responded to mismatches between
      eye and target positions, even when the animal made two different types of eye
      movements. This neuronal activity therefore does not appear to convey a command
      for a specific type of eye movement but instead encodes an error signal that
      could be used by multiple movements. The use of shared inputs is one possible
      strategy for ensuring that different movements share a common goal.

PMID- 9180079
TI  - Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine.
AB  - Two families of small peptides that bind to the human thrombopoietin receptor and
      compete with the binding of the natural ligand thrombopoietin (TPO) were
      identified from recombinant peptide libraries. The sequences of these peptides
      were not found in the primary sequence of TPO. Screening libraries of variants of
      one of these families under affinity-selective conditions yielded a 14-amino acid
      peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high
      affinity (dissociation constant approximately 2 nanomolar) that stimulates the
      proliferation of a TPO-responsive Ba/F3 cell line with a median effective
      concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl
      terminal linkage to a lysine branch produced a compound with an EC50 of 100
      picomolar, which was equipotent to the 332-amino acid natural cytokine in cell
      based assays. The peptide dimer also stimulated the in vitro proliferation and
      maturation of megakaryocytes from human bone marrow cells and promoted an
      increase in platelet count when administered to normal mice.

PMID- 9180080
TI  - Epilepsy and exacerbation of brain injury in mice lacking the glutamate
      transporter GLT-1.
AB  - Extracellular levels of the excitatory neurotransmitter glutamate in the nervous
      system are maintained by transporters that actively remove glutamate from the
      extracellular space. Homozygous mice deficient in GLT-1, a widely distributed
      astrocytic glutamate transporter, show lethal spontaneous seizures and increased
      susceptibility to acute cortical injury. These effects can be attributed to
      elevated levels of residual glutamate in the brains of these mice.

PMID- 9180081
TI  - Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of
      Pbs2p MAPKK.
AB  - Exposure of the yeast Saccharomyces cerevisiae to high extracellular osmolarity
      induces the Sln1p-Ypd1p-Ssk1p two-component osmosensor to activate a mitogen
      activated protein (MAP) kinase cascade composed of the Ssk2p and Ssk22p MAP
      kinase kinase kinases (MAPKKKs), the Pbs2p MAPKK, and the Hog1p MAPK. A second
      osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p
      MAPKKK. Although Ste11p also participates in the mating pheromone-responsive MAPK
      cascade, there was no detectable cross talk between these two pathways. The MAPKK
      Pbs2p bound to the Sho1p osmosensor, the MAPKKK Ste11p, and the MAPK Hog1p. Thus,
      Pbs2p may serve as a scaffold protein.

PMID- 9180082
TI  - Essential role of growth hormone in ischemia-induced retinal neovascularization.
AB  - Retinal neovascularization is the major cause of untreatable blindness. The role
      of growth hormone (GH) in ischemia-associated retinal neovascularization was
      studied in transgenic mice expressing a GH antagonist gene and in normal mice
      given an inhibitor of GH secretion (MK678). Retinal neovascularization was
      inhibited in these mice in inverse proportion to serum levels of GH and a
      downstream effector, insulin-like growth factor-I (IGF-I). Inhibition was
      reversed with exogenous IGF-I administration. GH inhibition did not diminish
      hypoxia-stimulated retinal vascular endothelial growth factor (VEGF) or VEGF
      receptor expression. These data suggest that systemic inhibition of GH or IGF-I,
      or both, may have therapeutic potential in preventing some forms of retinopathy.

PMID- 9180083
TI  - Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of
      frataxin.
AB  - The gene responsible for Friedreich's ataxia, a disease characterized by
      neurodegeneration and cardiomyopathy, has recently been cloned and its product
      designated frataxin. A gene in Saccharomyces cerevisiae was characterized whose
      predicted protein product has high sequence similarity to the human frataxin
      protein. The yeast gene (yeast frataxin homolog, YFH1) encodes a mitochondrial
      protein involved in iron homeostasis and respiratory function. Human frataxin
      also was shown to be a mitochondrial protein. Characterizing the mechanism by
      which YFH1 regulates iron homeostasis in yeast may help to define the pathologic
      process leading to cell damage in Friedreich's ataxia.

PMID- 9180084
TI  - Bimolecular exon ligation by the human spliceosome.
AB  - Intron excision is an essential step in eukaryotic gene expression, but the
      molecular mechanisms by which the spliceosome accurately identifies splice sites
      in nuclear precursors to messenger RNAs (pre-mRNAs) are not well understood. A
      bimolecular assay for the second step of splicing has now revealed that exon
      ligation by the human spliceosome does not require covalent attachment of a 3'
      splice site to the branch site. Furthermore, accurate definition of the 3' splice
      site in this system is independent of either a covalently attached polypyrimidine
      tract or specific 3' exon sequences. Rather, in this system 3' splice site
      selection apparently occurs with a 5' --> 3' directionality.

PMID- 9180085
TI  - Trans-kingdom transposition of the Drosophila element mariner within the
      protozoan Leishmania.
AB  - Transposable elements of the mariner/Tc1 family are postulated to have spread by
      horizontal transfer and be relatively independent of host-specific factors. This
      was tested by introducing the Drosophila mauritiana element mariner into the
      human parasite Leishmania major, a trypanosomatid protozoan belonging to one of
      the most ancient eukaryotic lineages. Transposition in Leishmania was efficient,
      occurring in more than 20 percent of random transfectants, and proceeded by the
      same mechanism as in Drosophila. Insertional inactivation of a specific gene was
      obtained, and a modified mariner element was used to select for gene fusions,
      establishing mariner as a powerful genetic tool for Leishmania and other
      organisms. These experiments demonstrate the evolutionary range of mariner
      transposition in vivo and underscore the ability of this ubiquitous DNA to
      parasitize the eukaryotic genome.

PMID- 9180086
TI  - HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft
      versus-leukemia.
AB  - In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a
      central therapeutic role in both graft-versus-leukemia (GvL) and immune
      reconstitution. However, their use is limited by the risk of severe graft-versus
      host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus
      induced lymphoma after T cell-depleted BMT were then treated with donor
      lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK)
      suicide gene. The transduced lymphocytes survived for up to 12 months, resulting
      in antitumor activity in five patients. Three patients developed GvHD, which
      could be effectively controlled by ganciclovir-induced elimination of the
      transduced cells. These data show that genetic manipulation of donor lymphocytes
      may increase the efficacy and safety of allo-BMT and expand its application to a
      larger number of patients.

PMID- 9180087
TI  - Catheter-based radiotherapy to inhibit restenosis after coronary stenting.
AB  - BACKGROUND: In animal models of coronary restenosis, intracoronary radiotherapy
      has been shown to reduce the intimal hyperplasia that is a part of restenosis. We
      studied the safety and efficacy of catheter-based intracoronary gamma radiation
      plus stenting to reduce coronary restenosis in patients with previous restenosis.
      METHODS: Patients with restenosis underwent coronary stenting, as required, and
      balloon dilation and were then randomly assigned to receive catheter-based
      irradiation with iridium-192 or placebo. Clinical follow-up was performed, with
      quantitative coronary angiographic and intravascular ultrasonographic
      measurements at six months. RESULTS: Fifty-five patients were enrolled; 26 were
      assigned to the iridium-192 group and 29 to the placebo group. Angiographic
      studies were performed in 53 patients (96 percent) at a mean (+/-SD) of 6.7+/-2.2
      months. The mean minimal luminal diameter at follow-up was larger in the iridium
      192 group than in the placebo group (2.43+/-0.78 mm vs. 1.85+/-0.89 mm, P=0.02).
      Late luminal loss was significantly lower in the iridium-192 group than in the
      placebo group (0.38+/-1.06 mm vs. 1.03+/-0.97 mm, P=0.03). Angiographically
      identified restenosis (stenosis of 50 percent or more of the luminal diameter at
      follow-up) occurred in 17 percent of the patients in the iridium-192 group, as
      compared with 54 percent of those in the placebo group (P= 0.01). There were no
      apparent complications of the treatment. CONCLUSIONS: In this preliminary, short
      term study of patients with previous coronary restenosis, coronary stenting
      followed by catheter-based intracoronary radiotherapy substantially reduced the
      rate of subsequent restenosis.

PMID- 9180088
TI  - Homozygous inactivation of the NF1 gene in bone marrow cells from children with
      neurofibromatosis type 1 and malignant myeloid disorders.
AB  - BACKGROUND: The risk of malignant myeloid disorders in young children with
      neurofibromatosis type 1 is 200 to 500 times the normal risk. The gene for
      neurofibromatosis type 1 (NF1) encodes neurofibromin, a protein that negatively
      regulates signals transduced by Ras proteins. Genetic and biochemical data
      support the hypothesis that NF1 functions as a tumor-suppressor gene in immature
      myeloid cells, but inactivation of both NF1 alleles has not been demonstrated in
      leukemic cells from patients with neurofibromatosis type 1. METHODS: Using an in
      vitro transcription and translation system, we screened bone marrow samples from
      18 children with neurofibromatosis type 1 and myeloid disorders for NF1 mutations
      that cause a truncated protein. Mutations were confirmed by direct sequencing of
      genomic DNA from the patients, and from their affected parents, in cases of
      familial neurofibromatosis type 1. RESULTS: Specimens from 9 of the 18 children
      contained abnormal peptide fragments, and truncating mutations of the NF1 gene
      were found in specimens from 8 of these children. The normal NF1 allele was
      absent in bone marrow samples from five of the eight children. We detected the
      same mutation in DNA from the affected parent of each child with familial
      neurofibromatosis type 1. CONCLUSIONS: Both alleles of the NF1 gene are
      inactivated in leukemic cells in some patients with neurofibromatosis type 1. NF1
      appears to function as a tumor-suppressor gene in immature myeloid cells.

PMID- 9180089
TI  - Images in clinical medicine. Trichobezoars.

PMID- 9180091
TI  - Mild perioperative hypothermia.

PMID- 9180090
TI  - Absence of association between insurance copayments and delays in seeking
      emergency care among patients with myocardial infarction.
AB  - BACKGROUND: The requirement of copayments for emergency care is thought to
      control costs by reducing "inappropriate" visits to the emergency department.
      However, requiring copayments may lead to adverse outcomes if patients delay
      seeking care for emergency conditions. To determine whether such requirements are
      associated with delays in seeking care, we examined the length of time from the
      onset of symptoms to arrival at the hospital among patients with myocardial
      infarction who did or did not have required insurance copayments. METHODS: All
      patients were enrolled in a single health maintenance organization (HMO) and
      presented with myocardial infarction at 1 of 19 hospitals in King County,
      Washington, from 1989 through 1994. There were 602 patients whose health
      insurance required a copayment for emergency department care (range, $25 to $100)
      and 729 patients with no copayment requirement. Data on the time to presentation
      were obtained from a review of ambulance and hospital records. RESULTS: The
      median length of time from the onset of symptoms to arrival at the hospital, as
      adjusted for age, sex, and race, was 135 minutes for the copayment group and 137
      minutes for the group with no copayment (95 percent confidence interval for the
      difference, -19 to +16 minutes). There was no significant association between the
      presence or absence of a copayment requirement and the time to arrival at the
      hospital after adjustment for calendar year, income, educational level, cardiac
      history, or clinical symptoms. Since some patients may be unaware of their
      copayment requirement, we performed a subgroup analysis of data on patients who
      had a previous visit to the emergency department with the same copayment status -
      that is, of patients who were likely to know about their copayment. This analysis
      also showed no significant association between the requirement for a copayment
      and delays in seeking treatment. CONCLUSIONS: For privately insured patients in
      this HMO, the requirement of modest, fixed copayments for emergency services did
      not lead to delays in seeking treatment for myocardial infarction.

PMID- 9180092
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 18-1997. A 78-year-old man with a sigmoid stricture after
      radiation treatment for prostatic cancer.

PMID- 9180093
TI  - Practicing medicine without a license--the new intrusions by Congress.

PMID- 9180094
TI  - Preventing coronary restenosis and complications.

PMID- 9180095
TI  - Cost sharing in the emergency department--is it safe? Is it needed?

PMID- 9180096
TI  - Ethics of a paired-kidney-exchange program.

PMID- 9180097
TI  - Systolic blood pressure revisited.
AB  - The clinical importance of systolic blood pressure (SBP) needs no emphasis. Its
      determinants are well known, but recent studies of one of these determinants,
      arterial distensibility, have led to results that now have clinical relevance.
      This review summarizes the role of arterial stiffness in ventricular-vascular
      coupling in the normal circulation and that disordered by aging and hypertension.
      The discussion defines the unfamiliar terms of compliance, distensibility and
      modulus and indicates how they are measured. Such measurements have increased our
      understanding of the parts played by the inhomogeneity of the arterial tree and
      reflected pressure waves in governing SBP. Elevated SBP is a recognized risk
      factor for cardiovascular complications among older patients, but when this
      elevation is due to a stiffened arterial tree, diastolic blood pressure (DBP) is
      necessarily reduced. Early epidemiologic studies in hypertension required a DBP >
      or = 90 mm Hg for hospital admission. They therefore excluded persons with high
      SBP, low DBP and very wide pulse pressure (PP). More recent inclusion of such
      patients has shown that elevation of SBP and PP is a strong predictor of
      cardiovascular risk. These considerations point to a possible redefinition of
      hypertension to include patients with lower DBP and to the inaccuracy but
      indispensability of the brachial artery pressure as a surrogate for aortic
      pressure--the pressure the heart sees. Finally, we review the known effects of
      available antihypertensive drugs on the arterial wall and indicate possible
      future directions of research stemming from wider understanding of the role of
      arterial distensibility in hypertension.

PMID- 9180098
TI  - Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and
      calcium channel blocking agents: a review of potential benefits and possible
      adverse reactions.
AB  - A review of recent studies suggests that the use of angiotensin-converting enzyme
      (ACE) inhibitors may be preferred (usually along with a diuretic drug) as initial
      therapy in several subsets of hypertensive patients (i.e., those with diabetes
      and nephropathy or with diminished left ventricular function with or without
      symptoms of heart failure). Limited long-term data are available for the
      angiotensin II receptor antagonists. The use of nondihydropyridine calcium
      channel blocking agents (CCBs) appears to reduce reinfarction in patients with
      ischemic heart disease (however, mortality is not reduced). Long-acting formulas
      of CCBs appear to decrease congestive heart failure in patients with dilated, but
      not ischemic, cardiomyopathy and to decrease strokes and arrhythmias in
      hypertensive subjects. Short-acting agents (primarily those that increase heart
      rate) may increase coronary heart disease events in hypertensive patients. There
      is little evidence at present that CCBs offer a major advantage over other
      antihypertensive agents or that they should be recommended as initial therapy,
      except in special situations.

PMID- 9180099
TI  - Cardiovascular toxicity of nicotine: implications for nicotine replacement
      therapy.
AB  - This review discusses the known cardiovascular effects of smoking and the effects
      of nicotine without tobacco smoke and interprets the available data on
      cardiovascular risk during nicotine replacement therapy (NRT). Nicotine gum and
      patches are now approved for over the counter sale in the United States. Smokers
      with cardiovascular disease are advised to seek physician counseling before using
      nicotine products, but information regarding the safety of these products in such
      patients is not readily available to most physicians. Nicotine may contribute to
      cardiovascular disease, presumably by hemodynamic consequences of sympathetic
      neural stimulation and systemic catecholamine release. However, there are many
      potential cardiovascular toxins in cigarette smoke other than nicotine. The doses
      of nicotine obtained by regular cigarette smoking generally exceed those
      delivered by NRTs, and the cardiovascular effects of nicotine are, in general,
      more intense when delivered rapidly by cigarette smoking than the slower delivery
      by transdermal nicotine or nicotine gum. Because the dose-cardiovascular response
      relation for nicotine is flat, the effects of cigarette smoking in conjunction
      with NRT are similar to those of cigarette smoking alone. Cigarette smoking
      increases blood coagulability, a major risk factor for acute cardiovascular
      events, whereas transdermal nicotine does not appear to do so. Clinical trials of
      NRT in patients with underlying, stable coronary disease suggest that nicotine
      does not increase cardiovascular risk. At worst, the risks of NRT are no more
      than those of cigarette smoking. The risks of NRT for smokers, even for those
      with underlying cardiovascular disease, are small and are substantially
      outweighed by the potential benefits of smoking cessation.

PMID- 9180100
TI  - Arterial reactivity is enhanced in genetic males taking high dose estrogens.
AB  - OBJECTIVES: We sought to assess whether high dose estrogen treatment is
      associated with enhanced arterial reactivity in genetic males. BACKGROUND:
      Although estrogens have been shown to enhance arterial reactivity in women, and
      are thereby thought to confer cardiovascular benefit, the vascular effects of
      long-term estrogen therapy in genetic males is unknown. METHODS: We studied the
      arterial physiology of 30 genetic males--15 male to female transsexuals receiving
      long-term high dose estrogen therapy and 15 healthy male control subjects matched
      for age, smoking history and vessel size. Using external vascular ultrasound,
      brachial artery diameter was measured at rest, after flow increase (causing
      endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an
      endothelium-independent dilator. Blood pressure, cholesterol and testosterone
      levels were also measured in each subject. RESULTS: Total testosterone and free
      testosterone index levels were lower in the transsexuals compared with the
      control subjects (p < 0.001). In contrast, EDD was significantly higher in the
      transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/-
      2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p =
      0.002). Total and high density lipoprotein cholesterol, blood pressure levels and
      baseline vessel size were similar in the two groups. On multivariate analysis,
      enhanced EDD was associated independently with estrogen therapy (p = 0.02) and
      with low total cholesterol (p = 0.04). An enhanced GTN response was also
      significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term
      treatment with high dose estrogens is associated with enhanced arterial
      reactivity in genetic males, which may be due to the effects of estrogen excess
      or androgen deprivation, or both.

PMID- 9180101
TI  - Long-term estrogen therapy improves vascular function in male to female
      transsexuals.
AB  - OBJECTIVES: This study sought to examine the effects of long-term estrogen
      therapy on vascular function in male to female transsexuals and to compare the
      findings with those observed in men and premenopausal women. BACKGROUND: Gender
      differences in coronary artery disease have largely been attributed to the
      beneficial effects of estrogen on vascular function and plasma lipids in women.
      However, the effects of estrogen on the male vasculature have not been widely
      studied. METHODS: We compared the effects of estrogen on vascular function in 14
      male to female transsexuals, 14 age-matched men and 15 premenopausal women. Flow
      mediated vasodilation and response to nitroglycerin were assessed in the brachial
      artery using noninvasive ultrasound. RESULTS: Flow-mediated vasodilation was
      similar in transsexuals and women but greater than that in men ([mean +/- SE]
      11.5 +/- 1.3% and 9.4 +/- 1.1% vs. 5.2 +/- 1.0% respectively, p < 0.005).
      Responses to nitroglycerin were also greater in transsexuals and women than in
      men (21.6 +/- 1.7% and 21.0 +/- 0.9% vs. 14.5 +/- 1.2%, respectively, p =
      0.0005). These differences persisted even after adjusting for vessel size.
      Despite similar total cholesterol levels, transsexuals had high density
      lipoprotein cholesterol levels similar to those in women and greater than those
      observed in men (1.76 +/- 0.12 and 1.82 +/- 0.11 mmol/liter vs. 1.35 +/- 0.07
      mmol/liter, respectively, p < 0.005). Moreover, triglyceride levels were greater
      in transsexuals than in men and women, and low density lipoprotein cholesterol
      (LDL-C) particle size was smaller (25.7 +/- 0.2 nm vs. 26.2 +/- 0.1 and 26.6 +/-
      0.1 nm, respectively, p = 0.0001). Serum testosterone (an index of estrogen
      therapy in transsexuals) was markedly suppressed in transsexuals and similar to
      that in women. Univariate analysis revealed that there was a strong inverse
      correlation between serum testosterone and flow-mediated vasodilation (r(s) = 
      0.48, p < 0.005). Multivariate analysis revealed that the best combination of
      predictors of flow-mediated vasodilation was serum testosterone, vessel size and
      LDL-C (R2 = 0.3, p < 0.005). CONCLUSIONS: Long-term estrogen therapy appears to
      improve vascular function in male to female transsexuals and occurs despite
      higher triglyceride levels and the presence of small, dense LDL-C. The beneficial
      effects of estrogen are not gender specific or solely mediated through
      endothelium-derived nitric oxide.

PMID- 9180102
TI  - Estrogen for men: reversal of cardiovascular misfortune?

PMID- 9180103
TI  - A prospective, randomized, double-blind multicenter trial of a single bolus
      injection of the novel modified t-PA E6010 in the treatment of acute myocardial
      infarction: comparison with native t-PA. E6010 Study Group.
AB  - OBJECTIVES: This prospective, randomized, double-blind multicenter trial
      evaluated the efficacy and safety of a single bolus injection of the novel
      modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute
      myocardial infarction compared with that of native t-PA. BACKGROUND: E6010 is a
      novel modified t-PA with a prolonged half-life (t1/2 alpha > or = 23 min)
      compared with native t-PA (t1/2 alpha = 4 min). E6010 can be administered in
      patients as a single intravenous bolus injection, and early recanalization can be
      expected. METHODS: The efficacy of E6010 was compared with that of native t-PA in
      199 patients with acute myocardial infarction who were treated within 6 h of
      onset in a prospective, randomized, double-blind multicenter trial. Patients were
      given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t
      PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2
      min, the remainder infused over 60 min). RESULTS: The primary end point was the
      recanalization rate of the infarct-related coronary artery at 60 min after the
      start of treatment. Time to reperfusion was shorter in the E6010 group than in
      the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3
      recanalization at 15, 30, 45 and 60 min after administration was observed in 37%,
      62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated
      patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated
      patients, respectively (p = 0.032 at 60 min). CONCLUSIONS: The present study
      indicates that, compared with native t-PA, a single bolus injection of E6010 over
      2 min produces a higher rate of early recanalization of the infarct-related
      coronary artery without fatal bleeding complications.

PMID- 9180104
TI  - Thrombolysis plus aortic counterpulsation: improved survival in patients who
      present to community hospitals with cardiogenic shock.
AB  - OBJECTIVES: We sought to explore the potential benefit of combining intraaortic
      balloon counterpulsation (IABP) with thrombolysis for acute myocardial infarction
      (MI) complicated by cardiogenic shock. BACKGROUND: In community hospitals, this
      condition is usually managed with thrombolysis alone. METHODS: We reviewed the
      charts of 335 patients from two community hospitals who presented with acute MI
      and had cardiogenic shock between 1985 and 1995. RESULTS: Of 46 patients who
      underwent thrombolysis within 12 h of acute infarction with confirmed cardiogenic
      shock, 27 underwent IABP and 19 did not. Age, systolic blood pressure with shock,
      pulmonary artery catheter use, pulmonary capillary wedge pressure and the
      incidence of diabetes mellitus and anterior MI did not differ between groups.
      Patients treated with IABP were somewhat more likely to have prior MI and had a
      significantly greater cardiac index (2.0 vs. 1.5 liters/min per m2, p = 0.04).
      Although no deaths occurred within 2 h of presentation, patients not treated with
      IABP tended to die earlier (6.8 +/- 5 vs. 23.8 +/- 19 h, p = 0.13). Patients
      treated with IABP had a significantly higher rate of community hospital survival
      (93% vs. 37%, p = 0.0002), and more of them were transferred for
      revascularization (85% vs. 37%). Of 30 patients transferred for
      revascularization, 27 underwent angioplasty or bypass surgery; hospital survival
      was 74%. Patients treated with IABP also had a significantly higher overall
      hospital and 1-year survival rate (67% vs. 32%, p = 0.019). CONCLUSIONS: Survival
      may be enhanced and transfer for revascularization facilitated when community
      hospitals use both thrombolysis and IABP to treat patients with acute MI
      complicated by cardiogenic shock.

PMID- 9180105
TI  - A prospective, randomized evaluation of prophylactic intraaortic balloon
      counterpulsation in high risk patients with acute myocardial infarction treated
      with primary angioplasty. Second Primary Angioplasty in Myocardial Infarction
      (PAMI-II) Trial Investigators.
AB  - OBJECTIVES: A large, international, multicenter, prospective, randomized trial
      was performed to determine the role of prophylactic intraaortic balloon pump
      (IABP) counterpulsation after primary percutaneous transluminal coronary
      angioplasty (PTCA) in acute myocardial infarction (AMI). BACKGROUND: Previous
      studies have suggested that routine IABP use after primary PTCA reduces infarct
      related artery reocclusion, augments myocardial recovery and improves clinical
      outcomes. METHODS: Cardiac catheterization was performed in 1,100 patients within
      12 h of onset of AMI at 34 clinical centers. Clinical and angiographic variables
      were used to stratify patients undergoing primary PTCA into high and low risk
      groups. High risk patients were then randomized to 36 to 48 h of IABP (n = 211)
      or traditional care (n = 226). The study had 80% power to detect a reduction in
      the primary end point from 30% to 20%. RESULTS: There was no significant
      difference in the predefined primary combined end point of death, reinfarction,
      infarct-related artery reocclusion, stroke or new-onset heart failure or
      sustained hypotension in patients treated with an IABP versus those treated
      conservatively (28.9% vs. 29.2%, p = 0.95). The IABP strategy conferred modest
      benefits in reduction of recurrent ischemia (13.3% vs. 19.6%, p = 0.08) and
      subsequent unscheduled repeat catheterization (7.6% vs. 13.3%, p = 0.05) but did
      not reduce the rate of infarct-related artery reocclusion (6.7% vs. 5.5%, p =
      0.64), reinfarction (6.2% vs. 8.0%, p = 0.46) or mortality (4.3% vs. 3.1%) and
      was associated with a higher incidence of stroke (2.4% vs. 0%, p = 0.03). IABP
      use did not result in enhanced myocardial recovery as assessed by paired
      admission to predischarge and 6-week rest and exercise left ventricular ejection
      fraction. CONCLUSIONS: In contrast to previous studies, a prophylactic IABP
      strategy after primary PTCA in hemodynamically stable high risk patients with AMI
      does not decrease the rates of infarct-related artery reocclusion or
      reinfarction, promote myocardial recovery or improve overall clinical outcome.

PMID- 9180107
TI  - Dose-ranging trial of enoxaparin for unstable angina: results of TIMI 11A. The
      Thrombolysis in Myocardial Infarction (TIMI) 11A Trial Investigators.
AB  - OBJECTIVES: The Thrombolysis in Myocardial Infarction (TIMI) 11A trial compared
      the safety and tolerability of two weight-adjusted regimens of subcutaneous
      injections of enoxaparin, a low molecular weight heparin, in patients with
      unstable angina/non-Q wave myocardial infarction (NQMI). BACKGROUND: The optimal
      dose of enoxaparin in patients with arterial disorders has not been established.
      METHODS: Patients with unstable angina/NQMI were treated over a 14-day period in
      an open label dose-ranging trial. During the in-hospital phase, patients received
      either 1.25 mg/kg body weight (dose tier 1) or 1.0 mg/kg (dose tier 2) of
      enoxaparin subcutaneously every 12 h. A fixed dose of either 60 mg (body weight >
      or = 65 kg) or 40 mg (body weight < 65 kg) was administered subcutaneously every
      12 h after hospital discharge. RESULTS: In an initial cohort of 321 patients
      (dose tier 1), the rate of major bleeding through 14 days was 6.5% and occurred
      predominantly at instrumented sites. In a second cohort of 309 patients (dose
      tier 2), the rate of major hemorrhage was reduced to 1.9%. In both dose tiers,
      only 3% to 5% of patients withdrew consent for subcutaneous injections during the
      home treatment phase. Through 14 days, the incidence of death, recurrent
      myocardial infarction or recurrent ischemia requiring revascularization was 5.6%
      in dose tier 1 and 5.2% in dose tier 2. CONCLUSIONS: An acute phase regimen of
      enoxaparin (1.0 mg/kg every 12 h) is associated with an acceptable rate of major
      hemorrhage during the in-hospital phase. There is a high rate of patient
      compliance during the home treatment phase. A Phase III trial is now underway to
      test the benefits of uninterrupted treatment with enoxaparin during both the in
      hospital and outpatient treatment phases.

PMID- 9180106
TI  - Association of angiotensin I-converting enzyme gene polymorphism with myocardial
      ischemia and patency of infarct-related artery in patients with acute myocardial
      infarction.
AB  - OBJECTIVES: We determined the influence of angiotensin I-converting enzyme (ACE)
      insertion (I)/deletion (D) polymorphism on the extent of myocardial ischemia in
      patients with acute myocardial infarction. BACKGROUND: The I/D polymorphism,
      which in part controls plasma and tissue expression of ACE, has been implicated
      in predisposition to myocardial infarction and ventricular remodeling. METHODS:
      I/D genotyping, predischarge adenosine-thallium-201 perfusion tomography and
      radionuclide angiography were performed in 113 patients (72 men, 41 women) with a
      diagnosis of acute myocardial infarction. A subgroup of 96 patients also
      underwent coronary angiography. RESULTS: Genotypes DD, ID and II were present in
      27, 56 and 30 patients, respectively. There was no significant difference in the
      baseline characteristics of patients, total creatine kinase, peak MB fraction,
      Killip class, mean ejection fraction or the number of diseased vessels in
      patients with the DD, ID or II genotype. However, the size of the total and the
      reversible perfusion defects was greater in those with DD than in those with ID
      or II genotype (total defect size [mean +/- SD] 33.7 +/- 22.5%, 29.5 +/- 19.2%
      and 22.2 +/- 16.0%, respectively [p = 0.022]; reversible defect size 18.0 +/-
      16.0%, 12.1 +/- 11.6% and 8.2 +/- 7.8%, respectively [p = 0.006]). Occlusion of
      the infarct-related artery was also more common in patients with DD genotype
      (odds ratio 3.9, 95% confidence interval 1.4 to 11.0). Multivariate analysis
      showed that the I/D genotype was an independent predictor of perfusion defect
      size and patency of the infarct-related artery (p = 0.001). CONCLUSIONS: DD
      genotype was associated with a larger ischemic defect and occlusion of the
      infarct-related artery. Patients with DD genotype, having a larger ischemic
      defect, are expected to be at a greater risk for subsequent cardiovascular
      events.

PMID- 9180108
TI  - Relation between clinical, angiographic and ischemic findings at baseline and
      ischemia-related adverse outcomes at 1 year in the Asymptomatic Cardiac Ischemia
      Pilot study. ACIP Study Group.
AB  - OBJECTIVES: We attempted to investigate the relation between patient
      characteristics and adverse outcome in patients with ischemia and clinically
      stable coronary artery disease (CAD). BACKGROUND: Evidence suggests that cardiac
      ischemia, detected by exercise stress testing (ETT) and ambulatory
      electrocardiographic (AECG) monitoring during daily living, identifies a subgroup
      of patients at increased risk for adverse outcome, but the relation between these
      ischemia findings and clinical and angiographic characteristics is largely
      unknown. METHODS: We examined the relation between clinical, angiographic and
      ischemia characteristics at entry with adverse outcome observed at 1 year in the
      558 patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.
      RESULTS: By the 12-month visit 13.1% of patients had an ischemia-related adverse
      clinical outcome that included death, nonfatal myocardial infarction or an
      ischemia-related hospital admission. Multivariate analysis identified only the
      number of AECG ischemic episodes at entry (odds ratio [OR] 1.06, 99% confidence
      interval [CI] 1.01 to 1.12, p = 0.002) as an independent predictor of outcome.
      Assignment to revascularization (as opposed to an initial medical treatment
      strategy) showed a trend (OR 0.56, 99% CI 0.26 to 1.2, p = 0.05). None of the
      other baseline clinical, exercise or angiographic variables examined provided
      additional information relative to adverse outcome. CONCLUSIONS: Determinants of
      adverse outcome, among clinically stable patients with CAD and ischemia induced
      by stress and daily life were magnitude of AECG ischemia before treatment and,
      possibly, initial treatment assignment. Among the many other characteristics
      examined, including age, symptom status and angiographic and exercise variables,
      none contributed additional independent prognostic information. These two simple
      variables, which may be modifiable, need further study in a larger trial.

PMID- 9180109
TI  - Hospital mortality in women and men with acute cardiac ischemia: a prospective
      multicenter study.
AB  - OBJECTIVES: This study sought to determine gender differences in hospital
      mortality in patients with acute cardiac ischemia. BACKGROUND: It is unclear why
      women experience higher mortality from acute myocardial infarction (AMI) than men
      and whether this applies to all patients with acute ischemia. METHODS: We
      analyzed data from a prospective multicenter study involving patients presenting
      to the emergency department (ED) with symptoms suggestive of acute ischemia.
      RESULTS: Of 10,783 patients, 5,221 (48.4%) were women. Mean age was 60.5 years
      for women and 56.9 for men (p < 0.001). Women had more hypertension (54.6% vs.
      45.9%, p < 0.001) and diabetes (23.3% vs. 17.0%, p < 0.001) than men but fewer
      previous AMIs (21.1% vs. 28.9%, p < 0.001). Acute ischemia was confirmed in 1,090
      women (20.8%) and 1,451 men (26.1%, p < 0.001), including AMI in 322 women (6.2%)
      and 572 men (10.3%, p < 0.001). Women with an AMI were in a higher Killip class
      than men: class I in 60.3% versus 72.2%, class II in 19.3% versus 16%, class III
      in 15.5% versus 8.7% and class IV in 5% versus 3.1%, respectively (p = 0.001).
      There was no significant difference in mortality from acute ischemia between
      genders (4.0% vs. 3.5%, p = 0.6), but there was a trend for higher AMI mortality
      in women (10.3% vs. 7.4%, p = 0.1). After controlling for age, diabetes, heart
      failure and presenting blood pressure, gender did not predict mortality from
      acute ischemia (odds ratio 0.9, 95% confidence interval 0.5 to 1.4, p = 0.5).
      CONCLUSIONS: Among patients presenting to the ED with acute cardiac ischemia,
      gender does not appear to be an independent predictor of hospital mortality. The
      trend for higher mortality in women from AMI can be explained by their older age,
      greater frequency of diabetes and higher Killip class on presentation.

PMID- 9180110
TI  - A reappraisal of exercise electrocardiographic indexes of the severity of
      ischemic heart disease: angiographic and scintigraphic correlates.
AB  - OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes
      generally presumed to signify severe ischemic heart disease (IHD) correlate with
      coronary angiographic and scintigraphic myocardial perfusion findings.
      BACKGROUND: In exercise testing, it is generally assumed that the early onset of
      ST segment depression and its occurrence at a low rate-pressure product (ischemic
      threshold); the amount of maximal ST segment depression; and a horizontal or
      downsloping ST segment and its prolonged recovery after exercise signify more
      severe IHD. However, the relation of these indexes to coronary angiographic and
      exercise myocardial perfusion findings in patients with IHD is unclear. METHODS:
      We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium
      201 single-photon emission computed tomographic (SPECT) exercise test in 66
      consecutive subjects with stable angina, > or = 70% stenosis of at least one
      coronary artery, normal rest ECG and left ventricular wall motion and a prior
      positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and
      the quantitative thallium-SPECT measures of the extent, maximal deficit and
      redistribution gradient of the perfusion abnormality were characterized. RESULTS:
      Maximal ST segment depression could not differentiate the number of diseased
      vessels; was not related to VD score, maximal thallium deficit or redistribution
      gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95%
      confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment
      depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p
      < 0.05), whereas the ischemic threshold had low inverse correlation only with VD
      score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution
      gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or
      downsloping compared with an upsloping ST segment did not demonstrate more severe
      angiographic and scintigraphic disease. Recovery time did not correlate with
      angiographic and scintigraphic findings, and correlations between angiographic
      and scintigraphic findings were also low or absent. CONCLUSIONS: In this
      homogeneous study group, the exercise ECG indexes did not necessarily signify
      more severe IHD by angiographic and scintigraphic criteria. Lack of concordance
      between the exercise ECG, angiography and myocardial scintigraphy suggests that
      these diagnostic modalities examine different facets of myocardial ischemia,
      underscoring the need for caution in the interpretation of their results.

PMID- 9180111
TI  - Percutaneous transluminal coronary angioplasty versus medical therapy for stable
      angina pectoris: outcomes for patients with double-vessel versus single-vessel
      coronary artery disease in a Veterans Affairs Cooperative randomized trial.
      Veterans Affairs ACME InvestigatorS.
AB  - OBJECTIVES: This study sought to assess outcomes of men with double-vessel
      coronary artery disease randomly assigned to treatment by percutaneous
      transluminal coronary angioplasty (PTCA) or medical therapy, compared with
      previously reported outcomes for men with single-vessel disease. BACKGROUND: We
      previously reported that PTCA provides better symptom relief and treadmill
      performance than medical therapy for men with stable angina pectoris due to
      single-vessel disease. Whether this advantage applies to patients with double
      vessel disease is unknown. METHODS: Male patients (n = 328) with stable angina
      pectoris and ischemia on treadmill testing were randomly assigned to PTCA or
      medical therapy; 101 patients had double-vessel disease, and 227 had single
      vessel disease. Symptoms, treadmill performance, quality of life score, coronary
      stenosis and myocardial perfusion were compared at baseline and at 6 months.
      Patients were followed up for up to 6 years and underwent additional treadmill
      testing 2 to 3 years after randomization. RESULTS: PTCA-treated and medically
      treated patients with double-vessel disease experienced comparable improvement in
      exercise duration (+1.2 vs. +1.3 min, respectively, p = 0.89), freedom from
      angina (53% and 36%, respectively, p = 0.09) and improvement of overall quality
      of life score (+1.3 vs. +4.4, respectively, p = 0.32) at 6 months compared with
      baseline. This contrasts with greater advantages favoring PTCA by these criteria
      in patients with single-vessel disease (p = 0.0001 to 0.02). Trends present at 6
      months persisted at late follow-up. Patients undergoing double-vessel dilation
      had less complete initial revascularization (45% vs. 83%) and greater average
      stenosis of worst lesions at 6 months (74% vs. 56%). Likewise, patients with
      double-vessel disease showed less improved myocardial perfusion imaging (59% vs.
      75%). CONCLUSIONS: PTCA is beneficial in male patients with double-vessel
      disease; however, we cannot demonstrate the same advantage over medical therapy
      seen in similar patients with single-vessel disease. Less complete
      revascularization and greater restenosis for patients having multiple dilations
      would account for these findings. Alternatively, a type 2 error might be
      operative. Technical advances since completion of this trial might improve these
      outcomes. These findings warrant further investigation in a larger trial.

PMID- 9180112
TI  - PTCA comes to the bifurcations in the road: what the VA has to offer.

PMID- 9180113
TI  - Antiplatelet effect of ticlopidine after coronary stenting.
AB  - OBJECTIVES: This study sought to investigate the contribution of ticlopidine to
      the inhibition of platelet activation after coronary stent placement. BACKGROUND:
      After coronary stenting, antiplatelet therapy with aspirin and ticlopidine
      improves stent patency compared with anticoagulation. However, the specific role
      of ticlopidine has not been elucidated. METHODS: After successful coronary stent
      placement, we randomized 22 patients to receive ticlopidine and aspirin
      (ticlopidine group) and 25 to receive aspirin alone (aspirin group). Surface
      expression on platelets of the activated fibrinogen receptor and of P-selectin
      was assessed by flow cytometry. RESULTS: In the aspirin group the percent of
      platelets with activated fibrinogen receptors increased between days 1 and 5 (p =
      0.001), whereas there were no substantial changes in the ticlopidine group. The
      percent of P-selectin-positive platelets did not change significantly in the
      aspirin group but decreased in the ticlopidine group (p = 0.019). At day 5 after
      the intervention, the percent of platelets with activated fibrinogen receptors in
      the ticlopidine group was significantly lower (median [interquartile range]: 8.5
      [3.1 to 17.8] vs. 18.1 [8.5 to 35.5], p = 0.025), and there was a trend to fewer
      P-selectin-positive platelets than in the aspirin group (5.8 [3.4 to 9.5] vs. 8.8
      [4.0 to 15.8], p = 0.073). CONCLUSIONS: Combined antiplatelet therapy with
      ticlopidine plus aspirin is superior to treatment with aspirin alone in
      suppressing platelet activation after coronary stenting.

PMID- 9180114
TI  - Role of coronary artery lumen enlargement in improving coronary blood flow after
      balloon angioplasty and stenting: a combined intravascular ultrasound Doppler
      flow and imaging study.
AB  - OBJECTIVES: This study sought to examine the mechanism of increasing coronary
      flow reserve after balloon angioplasty and stenting. BACKGROUND: Coronary
      vasodilatory reserve (CVR) does not improve after percutaneous transluminal
      coronary angioplasty in > or = 50% of patients, postulated to be due to impaired
      microvascular circulation or inadequate lumen expansion despite adequate
      angiographic results. METHODS: To demonstrate the role of coronary lumen
      expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was
      measured in 42 patients before and after balloon angioplasty and again after
      stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS)
      imaging of the target sites after angioplasty and stenting. CVR (velocity) was
      computed as the ratio of adenosine-induced maximal hyperemic to basal average
      peak velocity. RESULTS: The percent diameter stenosis decreased from (mean +/-
      SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting
      (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89
      +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent
      placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional
      area was significantly larger after stenting than after angioplasty (8.39 +/-
      2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to
      increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p <
      0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r =
      0.58, p < 0.0001). CONCLUSIONS: In most cases, increases in CVR were associated
      with increases in coronary lumen cross-sectional area. These data suggest that
      impaired CVR after angioplasty is often related to the degree of residual
      narrowing, which at times may not be appreciated by angiography. A
      physiologically complemented approach to balloon angioplasty may improve
      procedural outcome.

PMID- 9180115
TI  - Comparison of collateral vascular responses in the donor and recipient coronary
      artery during transient coronary occlusion assessed by intracoronary blood flow
      velocity analysis in patients.
AB  - OBJECTIVES: This study was designed to evaluate the hemodynamic variables of the
      collateral circulation during acute coronary occlusion. BACKGROUND: There is
      limited information on the physiology of the collateral circulation in coronary
      artery disease. METHODS: Angiography of the contralateral donor artery was
      performed before and during balloon coronary occlusion in 57 patients with one
      vessel disease. Recruitable collateral flow was assessed during coronary
      occlusion by blood flow analysis of the contralateral donor artery (n = 19) or
      the ipsilateral recipient artery (n = 15), or both (n = 23), using a Doppler
      catheter or guide wire. Ischemia was evaluated by the ST segment shift (> or =
      0.1 mV) on a 12-lead electrocardiogram at 1 min of coronary occlusion. RESULTS:
      The presence (n = 39), compared with the absence (n = 18), of recruitable
      collateral vessels was associated with an increase of blood flow velocity in the
      donor artery (20 +/- 19% vs. 4.8 +/- 5.9% [mean +/- SD], p = 0.003) and the
      recipient artery (velocity integral 7.2 +/- 5.5 vs. 2.8 +/- 2.2 cm, p = 0.02)
      related to a reduced relative collateral vascular resistance (9.2 +/- 10 vs. 20
      +/- 11, p = 0.003). Collateral flow in the donor artery yielded a similar
      predictive value for recruitability of collateral vessels as collateral flow
      determined in the recipient artery or the coronary wedge/aortic pressure ratio
      (areas under the receiver operating characteristics curves 0.76 +/- 0.07, 0.78 +/
      0.08, 0.77 +/- 0.07, respectively, p = NS). Collateral flow in the recipient
      artery was a better predictor for ischemia than collateral flow in the donor
      artery or angiographic grading of collateral vessels (areas 0.90 +/- 0.05, 0.64
      +/- 0.10, 0.73 +/- 0.07, respectively, p < 0.05). CONCLUSIONS: Coronary blood
      flow velocity analysis of the donor and recipient coronary arteries can
      characterize the dynamics of the collateral circulation during acute coronary
      occlusion. The protective effect of recruitable collateral vessels relates to an
      increase of flow in the donor and recipient coronary arteries due to a reduced
      collateral vascular resistance. This study underscores the importance of
      physiologic variables for the evaluation of the function of recruitable
      collateral vessels.

PMID- 9180116
TI  - Growth factors released into the coronary circulation after vascular injury
      promote proliferation of human vascular smooth muscle cells in culture.
AB  - OBJECTIVES: This study sought to 1) assess in vivo release of platelet-derived
      growth factor (PDGF) and basic fibroblast growth factor (bFGF) into the coronary
      circulation after vascular injury in human subjects; and 2) evaluate mitogenic
      effects of PDGF and bFGF on the patient's own vascular smooth muscle cells
      (VSMCs). BACKGROUND: Circumstantial evidence suggests involvement of PDGF and
      bFGF peptides in the neointimal response to vascular injury. To date, no study
      has shown biologically active growth factors within the coronary circulation
      after vascular injury in human subjects. METHODS: In 18 patients, plasma PDGF AB,
      platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG) levels were measured
      in coronary sinus blood obtained before and up to 30 min after angioplasty. In
      five patients undergoing atherectomy, coronary sinus serum was added to cultured
      VSMCs derived from atherectomy tissue to assess the mitogenic potential of the
      serum. Mitogenicity attributable to PDGF and bFGF was determined using
      neutralizing antibodies to these factors. PDGF A, PDGF B and bFGF were localized
      within the atherectomy tissue using immunocytochemical analysis. RESULTS: Before
      angioplasty, PDGF AB, PF4 and beta-TG levels were elevated threefold in patients
      scheduled for angioplasty compared with those in control patients (p < 0.01).
      Within 5 min of angioplasty, PDGF AB levels increased twofold and returned toward
      preangioplasty levels at 30 min; PF4 and beta-TG levels remained elevated. Serum
      obtained at 30 min after atherectomy showed a sixfold increase in mitogenicity
      compared with preatherectomy serum (p = 0.01). This increase in mitogenicity was
      reduced by 20%, 40% and 65% in the presence of neutralizing antibodies to PDGF,
      bFGF and PDGF + bFGF, respectively. PDGF A, PDGF B and bFGF were visualized
      within the intima of the atherectomy tissue. CONCLUSIONS: The change in plasma
      PDGF level is consistent with first-phase release of PDGF after vascular injury.
      The increase in mitogenicity of serum suggests that PDGF and bFGF are
      biologically active.

PMID- 9180118
TI  - Coronary calcification and coronary atherosclerosis: site by site comparative
      morphologic study of electron beam computed tomography and coronary angiography.
AB  - OBJECTIVES: We compared, on a site by site basis, the morphologic features of
      coronary calcifications determined by electron beam computed tomography (EBCT)
      and angiographically defined coronary atherosclerosis. BACKGROUND: Quantification
      of coronary calcification using EBCT is clinically useful for the prediction of
      coronary stenosis. However, the relation between calcification and angiographic
      findings has not been evaluated by site. METHODS: We studied 251 consecutive
      patients who underwent elective coronary angiography for suspected coronary
      artery disease by EBCT and analyzed findings by site. Coronary calcifications
      were classified according to their length and width versus the diameter of the
      coronary artery in which the calcification was observed as: none, spotty, long,
      wide and diffuse. RESULTS: Coronary calcifications were found in 666 (27%) of
      2,470 segments. The positive predictive value (PPV) of coronary calcification for
      significant stenosis (> or = 75% densitometric narrowing) and for all
      angiographically detectable atherosclerotic lesions in a segment was 0.36 and
      0.80, respectively. The PPV for significant stenosis and all atherosclerotic
      lesions was 0.04 and 0.17 in none, 0.18 and 0.59 in spotty, 0.32 and 0.87 in
      long, 0.40 and 0.84 in wide and 0.56 and 0.96 in diffuse calcifications,
      respectively. The PPV for both significant stenosis and all lesions differed
      significantly (p = 0.001) among the morphologic groups. Of the 105 eccentric
      significant stenoses, 54 (53%) were classified as long or diffuse calcifications.
      Of the 95 significant stenoses with multiple irregularities, 61 (64%) showed
      diffuse calcification. CONCLUSIONS: Morphologic evaluation of coronary
      calcifications using EBCT improved the prediction of coronary stenosis on a site
      by site basis and provided information related to angiographic morphology.

PMID- 9180117
TI  - Electron beam computed tomographic coronary calcium score cutpoints and severity
      of associated angiographic lumen stenosis.
AB  - OBJECTIVES: We sought to determine a range of cutpoints for coronary calcium
      scores measured by electron beam computed tomography (EBCT) in predicting the
      likely severity of associated angiographic coronary artery stenoses. BACKGROUND:
      EBCT can quantify coronary calcium and allow the estimation of atherosclerotic
      plaque burden, but use of the calcium score to define lumen narrowing is
      controversial. METHODS: A total of 213 patients (mean [+/- SD] age 50 +/- 9
      years) underwent coronary angiography and EBCT. Maximal percent diameter stenosis
      in any artery was paired with total coronary calcium score. Receiver operating
      characteristic (ROC) curve analysis was done using definitions of "disease" for
      maximal stenosis from > or = 20% to 100%, and the corresponding score cutpoints
      were determined for 90% sensitivity, 90% specificity or "optimal" sensitivity and
      specificity. RESULTS: ROC curve areas ranged from a mean (+/- SE) of 0.91 +/-
      0.02 for > or = 20% stenosis to 0.83 +/- 0.03 for 100% stenosis. Optimal calcium
      score cutpoints consisted of nonoverlapping values ranging from 15 for > or = 20%
      stenosis to 327 for 100% stenosis, whereas sensitivities and specificities ranged
      from 78% to 84%, depending on maximal stenosis severity. Calcium score cutpoints
      for 90% sensitivity and 90% specificity were also nonoverlapping and ranged from
      3 and 27, respectively, for > or = 20% stenosis to 154 and 945, respectively, for
      100% stenosis; corresponding specificities and sensitivities ranged from 40% to
      78%. CONCLUSIONS: These data define the ranges for EBCT coronary calcium score
      cutpoints that predict the likely severity of associated maximal angiographic
      stenosis severity to a high sensitivity, high specificity or optimal
      sensitivity/specificity. These cutpoints potentially can be used in conjunction
      with clinical variables to predict the severity of lumen narrowing in patients
      undergoing assessment for coronary artery disease.

PMID- 9180119
TI  - Coronary revascularization and cardiac catheterization in the United States:
      trends in racial differences.
AB  - OBJECTIVES: We sought to determine whether racial differences in rates of
      coronary artery bypass graft surgery (CABG), percutaneous transluminal coronary
      angioplasty (PTCA) and cardiac catheterization decreased after 1980. BACKGROUND:
      Many reports of racial differences in utilization of CABG have been published
      since 1982. However, changes in the relative utilization of revascularization
      over time have received little attention. METHODS: Data from the National
      Hospital Discharge Survey were examined for the years 1980 through 1993.
      Estimated numbers of procedures performed in nonfederal U.S. hospitals were used
      to compute age-adjusted rates per 100,000 population by year and race for
      patients 35 to 84 years old. RESULTS: In patients 35 to 84 years old, the rate of
      CABG increased in blacks and whites between 1980 and 1993. Between 1986 and 1993,
      there was little change in the black/white ratio of age-adjusted rates (0.23 in
      1980 through 1985 combined, 0.38 in 1986 and 0.43 in 1993). An apparent increase
      from 0.23 in 1980 through 1985 combined may have been due to sampling variation.
      Despite rapid increases in rates of PTCA in both races, no increase in the
      black/white ratio was noted (0.57 in 1993). However, the rate of inpatient
      cardiac catheterization increased more rapidly in blacks than in whites. This
      resulted in an increase in the black/white ratio of age-adjusted rates from 0.42
      in 1980 to 0.91 in 1993. CONCLUSIONS: Rates of CABG, cardiac catheterization and
      especially PTCA increased between 1980 and 1993, a period during which racial
      disparities in the procedures became widely known. Despite apparent increases in
      the black/white ratio for inpatient cardiac catheterization, large racial
      disparities in the utilization of CABG and PTCA persist and require further
      evaluation and possible intervention.

PMID- 9180120
TI  - Predictors of graft patency 3 years after coronary artery bypass graft surgery.
      Department of Veterans Affairs Cooperative Study Group No. 297.
AB  - OBJECTIVES: The purpose of this analysis was to define the factors that predict 3
      year graft patency. BACKGROUND: The success of coronary artery bypass graft
      surgery (CABG) is dependent on vein graft patency after the operation. It has
      been well established by a series of Department of Veterans Affairs Cooperative
      Trials that aspirin (325 mg daily) improves saphenous vein graft patency early (7
      to 10 days) and at 1 year, but not at 3 years after CABG. This analysis, based on
      one of these trials, defined factors that predict 3-year graft patency. METHODS:
      This analysis consisted of 266 patients, with 656 grafts that were patent 7 to 10
      days after the operation, who underwent 3-year catheterization. To determine
      which patient-specific and/or graft-specific factors, or both, predict graft
      occlusion, a multivariate logistic regression analysis in terms of latent
      variables was used. It yielded a model that also took into account possible
      intraclass correlations. RESULTS: For a vein graft that was patent at 7 to 10
      days after the operation, the positive predictors, according to univariate
      analysis, for that graft being patent at 3 years were cross-clamp time < or = 80
      min (p < 0.001), vein preservation solution temperature < or = 5 degrees C (p =
      0.009), bypass time < or = 2 h (p = 0.042), number of proximal anastomoses < or =
      2 (p = 0.018), operation time < or = 5 h (p = 0.044) and continuous versus
      intermittent cross-clamp technique (p = 0.024). There was also a trend with
      regard to recipient artery diameter > 1.5 mm (p = 0.063), serum cholesterol < or
      = 225 mg/dl (p = 0.084) and single versus sequential or Y vein graft (p = 0.060).
      Factors not predictive of 3-year patency were age, race, smoking history, high
      density lipoprotein cholesterol, vein source (thigh vs. calf), coronary artery
      grafted and aspirin treatment. Of all the predictors obtained in the univariate
      analysis, the only variables that were sufficient to yield a good model within
      the multivariate analysis were solution temperature (p = 0.004), serum
      cholesterol (p = 0.024), number of proximal anastomoses (p = 0.032) and recipient
      artery diameter (p = 0.034). CONCLUSIONS: For a patient with patent vein grafts 7
      to 10 days after the operation, predictors of 3-year graft patency are more
      closely related to operative techniques and underlying disease and not to aspirin
      treatment.

PMID- 9180121
TI  - Akinetic versus dyskinetic postinfarction scar: relation to surgical outcome in
      patients undergoing endoventricular circular patch plasty repair.
AB  - OBJECTIVES: This retrospective study attempted to relate surgical outcome with
      the extent and type of preoperative wall motion asynergy in patients with
      postinfarction myocardial scar who underwent endoventricular circular patch
      plasty repair and associated coronary grafting. BACKGROUND: Left ventricular (LV)
      pump function improvement is difficult to predict after aneurysmectomy, for
      either akinetic or dyskinetic scar, and previous studies have reported that the
      absence of paradoxic systolic motion correlates with higher operative mortality
      and no improvement in pump function. METHODS: Two hundred forty-five patients who
      underwent endoventricular circular patch plasty repair and associated coronary
      grafting were retrospectively selected if they had technically adequate right and
      left anterior LV angiograms before the operation. All had right and left cardiac
      catheterization. The centerline method was applied to preoperative right anterior
      oblique LV angiography to assess the absolute motion of the chords and the
      percent length of the perimeter showing a fractional shortening <2 SD from the
      normal mean value (extent of asynergy ([A%]). RESULTS: The overall perioperative
      mortality rate was 6%; 120 patients had akinetic and 125 had dyskinetic scar, and
      no differences were found among the groups in terms of all the clinical and
      hemodynamic variables collected in the study. Patients with a large scar (A%
      >60), either akinetic or dyskinetic, had a higher perioperative mortality rate
      (12%) than patients with a small scar (2.2%). After the operation, the ejection
      fraction (EF) increased from 36 +/- 13% to 50 +/- 13% (mean +/- SD), and
      pulmonary pressures significantly decreased. End-diastolic volume decreased from
      199 +/- 75 to 89 +/- 36 ml/m2. Patients with a large akinetic scar had the most
      severely impaired preoperative function (largest ventricular volumes and highest
      pulmonary mean pressure); nevertheless, they had an impressive improvement in
      function (EF from 25 +/- 9% to 41 +/- 12%), not different from that observed with
      large dyskinetic scarring (EF from 26 +/- 7% to 46 +/- 11%). CONCLUSIONS:
      Surgical outcome of endoventricular circular patch plasty repair for
      postinfarction myocardial scar relates to the extent of LV asynergy rather than
      to the presence or absence of dyskinesia. Patients with a large akinetic scar and
      severely depressed pump function benefit from a relatively simple surgical
      procedure previously reserved only for dyskinetic aneurysm. The reduction of wall
      tension and oxygen demand, owing to the marked decrease of volumes, and the
      increase in oxygen supply, owing to revascularization, may play a major role in
      improving pump function.

PMID- 9180122
TI  - QT dispersion as a marker of risk in patients awaiting heart transplantation.
AB  - OBJECTIVES: The objectives of this study were to determine whether a signal
      averaged electrocardiogram (SAECG) or measurement of interlead variability of QT
      intervals on an electrocardiogram (ECG) obtained at the time of wait-listing
      could provide prognostic value with respect to cardiac death during the waiting
      period. BACKGROUND: Because heart transplantation is a life-saving but limited
      resource, there remains an urgent need to identify those patients at greatest
      risk of dying while awaiting heart transplantation as part of the strategy to
      optimize the allocation of donor organs to those in greatest need. This study was
      undertaken to prospectively identify clinical, ECG or SAECG variables that might
      predict mortality during the waiting period. METHODS: Of 108 consecutive patients
      referred for heart transplant evaluation, 80 were placed on a waiting list, at
      which time a standard 12-lead ECG and a SAECG were recorded. In this cohort of 80
      patients, QT dispersion was characterized from the 12-lead ECG as either the
      maximal-minimal QT interval (QTDISP) or as the coefficient of variation of all QT
      intervals (QTCV). RESULTS: During the 25-month follow-up period (mean time on
      waiting list, 201 days), the mortality rate was 27%/year, divided equally between
      heart failure and sudden deaths. No clinical variable identified at entry
      predicted mortality. QTDISP and QTCV were strong mortality predictors, with a 4.1
      fold increase in mortality in patients with QTDISP > 140 ms compared with those
      patients with QTDISP < or = 140 ms (95% CI 1.1 to 14.9), whereas a QTCV > or = 9%
      also predicted a 4.1-fold increased risk of death (95% CI 1.4 to 11.8). Although
      88% of all SAECGs were abnormal, no patient with a normal SAECG died suddenly
      during the waiting period. CONCLUSIONS: Indexes of QT dispersion provide a means
      of stratifying a patient's risk of dying while awaiting heart transplantation and
      may help to establish priority on a heart transplant waiting list.

PMID- 9180123
TI  - Clinical correlates and prognostic significance of the ventilatory response to
      exercise in chronic heart failure.
AB  - OBJECTIVES: This study sought to investigate the clinical characteristics of
      patients with chronic heart failure and an increased ventilatory response to
      exercise and to examine the prognostic usefulness of this response. BACKGROUND:
      The ventilatory response to exercise is increased in many patients with chronic
      heart failure and may be characterized by the regression slope relating minute
      ventilation to carbon dioxide output (VE-VCO2 slope) during exercise. METHODS:
      One hundred seventy-three consecutive patients (155 men; mean [+/-SD] age 59.8 +/
      11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 +/-
      14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5
      +/- 7.3 ml/kg per min; VE-CO2 slope 34.8 +/- 10.6) over a 2-year period. Using
      1.96 standard deviations above the mean VE-VCO2 slope of 68 healthy age-matched
      subjects (mean slope 26.3 +/- 4.1), we defined a high ventilatory response to
      exercise as a slope >34. RESULTS: Eighty-three patients (48%) had an increased VE
      VCO2 slope (mean 43.1 +/- 8.9). There was a difference in age (62.2 vs. 57.3
      years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p <
      0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7
      ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55,
      p = 0.002) between these patients and those with a normal slope. In the
      univariate Cox proportional hazards model, the E-VCO2 slope was an important
      prognostic factor (p < 0.0001). In the multivariate Cox analyses using several
      variables (age, peak oxygen consumption, VE-VCO2 slope and LVEF), the VE-VCO2
      slope gave additional prognostic information (p = 0.018) beyond peak oxygen
      consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a
      survival rate of 95% in patients with a normal VE-VCO2 slope compared with 69% in
      those with a high slope (p < 0.0001). CONCLUSIONS: A high VE-VCO2 slope selects
      patients with more severe heart failure and is an independent prognostic marker.
      The VE-VCO2 slope may be used as a supplementary index in the assessment of
      patients with chronic heart failure.

PMID- 9180124
TI  - Effect of high intensity exercise training on central hemodynamic responses to
      exercise in men with reduced left ventricular function.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of high intensity
      exercise training on left ventricular function and hemodynamic responses to
      exercise in patients with reduced ventricular function. BACKGROUND: Results of
      studies on central hemodynamic adaptations to exercise training in patients with
      chronic heart failure have been contradictory, and some research has suggested
      that training causes further myocardial damage in these patients after a
      myocardial infarction. METHODS: Twenty-five men with left ventricular dysfunction
      after a myocardial infarction or coronary artery bypass graft surgery were
      randomized to an exercise training group (mean age +/- SD 56 +/- 5 years, mean
      ejection fraction [EF] 32 +/- 7%, n = 12) or a control group (mean age 55 +/- 7
      years, mean EF 33 +/- 6%, n = 13). Patients in the exercise group performed 2 h
      of walking daily and four weekly sessions of high intensity monitored stationary
      cycling (40 min at 70% to 80% peak capacity) at a residential rehabilitation
      center for a period of 2 months. Ventilatory gas exchange and upright hemodynamic
      measurements (rest and peak exercise cardiac output; pulmonary artery, wedge and
      mean arterial pressures; and systemic vascular resistance) were performed before
      and after the study period. RESULTS: Maximal oxygen uptake (VO2max) increased by
      23% after 1 month of training, and by an additional 6% after month 2. The
      increase in VO2max in the trained group paralleled an increase in maximal cardiac
      output (12.0 +/- 1.8 liters/min before training vs. 13.7 +/- 2.5 liters/min after
      training, p < 0.05), but maximal cardiac output did not change in the control
      group. Neither stroke volume nor hemodynamic pressures at rest or during exercise
      differed within or between groups. Rest left ventricular mass, volumes and EF
      determined by magnetic resonance imaging were unchanged in both groups.
      CONCLUSIONS: High intensity exercise training in patients with reduced left
      ventricular function results in substantial increases in VO2max by way of an
      increase in maximal cardiac output combined with a widening of maximal
      arteriovenous oxygen difference, but not changes in contractility. Training did
      not worsen hemodynamic status or cause further myocardial damage.

PMID- 9180125
TI  - Angiotensin-converting enzyme inhibitors potentiate preconditioning through
      bradykinin B2 receptor activation in human heart.
AB  - OBJECTIVES: This study was designed to determine whether angiotensin-converting
      enzyme (ACE) inhibitors play a role in cardioprotection in a human model of
      preconditioning. BACKGROUND: Recent studies have suggested that bradykinin may
      contribute to the protective effects of preconditioning in animal models. ACE
      inhibitors are known to inhibit the degradation of bradykinin and hence may be
      able to potentiate the effect of preconditioning. METHODS: We examined the
      effects of the ACE inhibitors captopril and lisinopril in combination with a
      subthreshold preconditioning stimulus (i.e., insufficient to have any protective
      effects alone). Human atrial trabeculae were superfused with Krebs buffer and
      paced at 1 Hz. They were subjected to a full or subthreshold preconditioning
      stimulus consisting of either 3 or 1.5 min of simulated ischemia and 7 min of
      reoxygenation. In each instance, this stimulus was followed by 90 min of
      simulated ischemia and 2 h of reoxygenation. In addition, the subthreshold
      preconditioned group had 20 min of previous ACE inhibitor treatment. RESULTS:
      Recovery of contractile function (percent of baseline) was 22 +/- 1% (mean +/-
      SEM) in the control group versus 61 +/- 1% in the preconditioned group. The
      subthreshold preconditioned group and the ACE inhibitor-alone groups did not
      exhibit any protection; however, in combination, the protection was significant
      (71 +/- 4% in the captopril group, 58 +/- 8% in the lisinopril group, p < 0.005)
      compared with the control group. There was no significant difference between
      these values and recovery after the full preconditioning stimulus. Furthermore,
      Hoe 140, a specific bradykinin B2 receptor antagonist, abolished the protection.
      CONCLUSIONS: To our knowledge, these are the first results in human muscle to
      suggest that ACE inhibitors may augment ischemic preconditioning, possibly
      through B2 receptor activation.

PMID- 9180126
TI  - Differential activation of cardiac and peripheral sympathetic nervous system by
      nifedipine: role of pharmacokinetics.
AB  - OBJECTIVES: We sought to study the effects of short-acting and long-acting
      nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood
      pressure (BP) of normotensive subjects under baseline conditions and during SNS
      stimulation. BACKGROUND: Calcium channel antagonists in different pharmacokinetic
      formulations are widely used in patients with coronary artery disease or
      hypertension. Short-acting formulations activate the SNS, an action that may be
      disadvantageous in patients with coronary disease, especially if left ventricular
      function is impaired. The effects of slow-release formulations on the SNS are
      unknown. METHODS: We used microneurography to investigate the influence of
      nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic
      nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy
      volunteers. RESULTS: Peak plasma levels after short-acting and slow-release
      nifedipine were achieved within 60 min and 330 min, respectively. Short-acting
      (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly
      activated MSA and increased plasma norepinephrine; plasma endothelin increased
      only with slow-release nifedipine. HR increased after short-acting nifedipine,
      but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade
      of cardiac sympathetic activity (with esmolol) led to similar decreases in HR
      with or without nifedipine, whereas parasympatholysis (with atropine) led to
      similar increases in HR with or without nifedipine. The cold pressor test
      markedly increased MSA in all treatment groups and further increased MSA beyond
      the increase induced by nifedipine. CONCLUSIONS: Nifedipine markedly increased
      MSA, but not SSA, independently of drug release formulation. In contrast, HR
      increased with short-acting, but not with slow-release, nifedipine. Therefore,
      nifedipine activates cardiac and peripheral sympathetic nerves differently
      depending on pharmacokinetics. These effects of nifedipine may be disadvantageous
      in cardiac patients with increased sympathetic activity or congestive heart
      failure, or both.

PMID- 9180127
TI  - Exercise tolerance in patients with Ebstein's anomaly.
AB  - OBJECTIVES: The purpose of this study was to identify the determinants of
      exercise tolerance in patients with Ebstein's anomaly. BACKGROUND: Patients with
      Ebstein's anomaly of the tricuspid valve may have exercise limitation that
      improves after surgical repair. METHODS: One hundred seventeen patients performed
      cycle ergometry for a total of 124 tests (preoperative test in 76 patients,
      postoperative test in 23, test but no operation in 18, preoperative and
      postoperative test in 7). Multiple linear regression analysis was used to
      identify predictors of maximal oxygen uptake, oxygen saturation and heart rate at
      peak exercise. RESULTS: Age at the time of exercise ranged from 6 to 60 years
      (median 15). An atrial septal defect was present in 67 patients (88%)
      preoperatively. Compared with the preoperative group, the postoperative group had
      significantly higher maximal oxygen uptake (mean [+/- SD] 20.5 +/- 7.4 vs. 25.3
      +/- 7.0 ml/kg body weight per min, p = 0.006). Postoperative rest and exercise
      blood oxygen saturation was higher than that measured preoperatively (p =
      0.0001). Six of seven patients tested before and after the operation showed
      improved exercise tolerance. Preoperatively, major predictors of maximal oxygen
      uptake were oxygen saturation at rest (p = 0.01) and age (p = 0.0001).
      Preoperatively, the major predictor of oxygen saturation at peak exercise was
      rest oxygen saturation (p = 0.0001), and major predictors of peak exercise heart
      rate were rest heart rate (p = 0.01) and rest oxygen saturation (p = 0.01). In
      the postoperative group, predictors of maximal oxygen uptake included age at
      exercise testing, male gender and heart size. CONCLUSIONS: Definitive operation
      for Ebstein's anomaly results in improved exercise tolerance. Before the
      operation, rest oxygen saturation is the major predictor of exercise tolerance,
      oxygen saturation at peak exercise and peak heart rate. Postoperatively, age,
      gender and heart size influenced maximal oxygen uptake.

PMID- 9180128
TI  - Proportionate reversible decreases in systolic function and myocardial oxygen
      consumption after modest reductions in coronary flow: hibernation versus
      stunning.
AB  - OBJECTIVES: This study sought to determine whether modest short-term reductions
      in coronary flow can produce subsequent proportionate reductions in myocardial
      function and O2 consumption compatible with myocardial hibernation. BACKGROUND:
      Acute studies indicate that myocardial energy utilization can be downregulated
      during moderate flow reduction. Whether this apparently beneficial adjustment
      persists into the reperfusion period is unsettled because most postischemic
      contractile dysfunction has been presumed to represent stunned or irreversibly
      injured myocardium. METHODS: Responses of regional myocardial function and O2
      consumption were assessed in chronically instrumented dogs after approximately
      50% reductions in flow for 2 h (n = 8) or repeated 2-min total coronary
      occlusions (n = 6). RESULTS: When unrestricted perfusion was restored after
      sustained partial occlusions, regional function and O2 consumption stabilized at
      proportionate, systematically decreased levels ([mean +/- SEM] 80 +/- 3.1% and 81
      +/- 5.1% of control values, both p < 0.05) and then returned to control values
      within 24 h. Similar proportionate reductions occurred after as few as five
      cycles of brief total occlusion (79 +/- 5.1% and 83 +/- 1.6% of control values,
      both again p < 0.05); these persisted with additional occlusions and then
      returned to baseline values within 3 h. The absence of irreversible injury was
      documented histologically in both series. Sham animals (n = 5) showed no changes
      in regional function or O2 consumption throughout similar experimental periods.
      CONCLUSIONS: Moderate decreases in coronary flow or repeated brief coronary
      occlusions can be followed by proportionate reversible reductions in regional
      systolic function and O2 consumption compatible with the traditional definition
      of myocardial hibernation. These findings emphasize the complexity of myocardial
      responses to flow restriction and call attention to limitations in characterizing
      reversibly hypocontractile myocardium as simply hibernating or stunned.

PMID- 9180129
TI  - Functional myocardial perfusion abnormality induced by left ventricular
      asynchronous contraction: experimental study using myocardial contrast
      echocardiography.
AB  - OBJECTIVES: The aim of this study was to clarify how myocardial perfusion is
      impaired by asynchronous contraction. BACKGROUND: False septal hypoperfusion is
      noted in some patients with left bundle branch block. METHODS: Eight dogs were
      examined with epicardial pacing at the left ventricular posterior wall, the right
      ventricular anterior wall and, as a control, the right atrial appendage. The
      pacing rate was 80, 110 and 150 beats/min (bpm). Myocardial perfusion was
      assessed by contrast echocardiography. RESULTS: Left ventricular pacing at 80 and
      110 bpm did not change systolic wall thickening or contrast intensity at the
      pacing site, although an early excitation notch was noted at the pacing site.
      However, at 150 bpm, systolic thickening was impaired (23.3 +/- 4.2% vs. 37.0 +/-
      2.6% during atrial pacing, p < 0.05), and the peak intensity ratio of the pacing
      site to the ventricular septum was significantly decreased (24.1 +/- 5.7% vs.
      37.0 +/- 2.8% at a pacing rate of 80 bpm, p < 0.01). The peak intensity ratio
      correlated with systolic wall thickening at the pacing site (y = 0.413 x -0.028,
      r = 0.81, p < 0.0001). However, right ventricular pacing did not change either
      systolic thickening or the peak intensity ratio at any pacing rate, although an
      early excitation notch was noted on the ventricular septum. CONCLUSIONS: Wall
      motion abnormalities after early excitation vary depending on the pacing mode.
      When tachycardia induces regional wall motion abnormalities, the ventricular wall
      of the pacing site is functionally hypoperfused.

PMID- 9180130
TI  - Electrophysiologic effects of sodium channel blockade on anisotropic conduction
      and conduction block in canine myocardium: preferential slowing of longitudinal
      conduction by flecainide versus disopyramide or lidocaine.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of sodium
      channel blockade on anisotropic excitation propagation in the intact canine left
      ventricle. BACKGROUND: Anisotropic ventricular conduction- electric conductivity
      dependent on the myocardial fiber direction-is one of the important mechanisms of
      ventricular arrhythmia. However, the effects of sodium channel blockade,
      especially the differential effect of a subclass of this agent, on the
      anisotropic properties remain unknown. METHODS: In 28 anesthetized, open chest
      dogs, a small cannula was inserted into the left anterior descending coronary
      artery. Saline (control), disopyramide, lidocaine or flecainide was infused
      selectively into the cannula. An array of 64 epicardial electrodes was placed on
      the anterior surface of the ventricle. Activation time (AT) was measured along
      the longitudinal (L) and transverse (T) directions. RESULTS: High dose flecainide
      (100 microg/kg body weight per min) delayed the AT along the L direction markedly
      (mean [+/-SE] 227 +/- 38%, p < 0.02) and mildly (121 +/- 10%, p < 0.02) along the
      T direction in regular beats (p < 0.007, L vs. T). Lidocaine and disopyramide did
      not show direction-dependent prolongation of the AT on regular beats. When
      examined on premature beats, AT was delayed, depending on the coupling interval
      and the fiber direction when saline, flecainide or lidocaine was infused. The
      conduction blocks along the L direction were observed in three of seven dogs on
      regular beats after flecainide and ventricular fibrillation ensued in two of
      these three dogs. CONCLUSIONS: A peculiar slowing of L conduction by flecainide
      may relate to the character of proarrhythmia.

PMID- 9180131
TI  - Drug clearance and arterial uptake after local perivascular delivery to the rat
      carotid artery.
AB  - OBJECTIVES: We attempted to characterize how drug released into the perivascular
      space enters the arterial wall and how it is cleared from the local environment.
      BACKGROUND: Drug released into the perivascular space can enter the artery either
      from the adventitial aspect or from the lumen after absorption by the
      extraarterial capillaries and mixing within the systemic circulation. Some
      investigators suggest that this latter mechanism dominates, and they question
      whether local drug release is synonymous with local deposition. METHODS: We
      investigated both the pathways by which adventitially released drug is cleared
      from the perivascular space and those by which drug enters the blood vessel wall.
      Inulin was used to follow drug release from implanted devices and subsequent
      entry to the circulation, because of its first-pass urinary excretion. Heparin
      was used to follow arterial deposition because of its vasoactivity and tissue
      binding properties. The different potential pathways of drug entry and egress
      were systematically removed and the effects on metabolism and deposition
      determined. RESULTS: Ligature occlusion of the artery did not decrease inulin
      excretion or heparin deposition. Extravascular wraps designed to shield the
      device from extramural capillaries reduced inulin excretion rates 10-fold but did
      not alter heparin deposition into the vessel wall. The deposition of drug after
      perivascular delivery was 500 times higher than after intraperitoneal
      administration. CONCLUSIONS: Although almost all the drug released into the
      perivascular space is cleared through the extravascular capillaries, virtually
      all the deposited drug diffuses directly from the perivascular space, and little
      arrives from the endovascular aspect. These data support the view that local drug
      release leads directly to increased local drug concentration.

PMID- 9180132
TI  - The Josef Steiner Lecture: CDKs and cell-cycle control in fission yeast:
      relevance to other eukaryotes and cancer.

PMID- 9180133
TI  - Cancer--a matter of life and cell death.

PMID- 9180134
TI  - The 1st UICC symposium on the molecular epidemiology of cancer. Union
      Internationale Contre le Cancer.

PMID- 9180135
TI  - Human papillomavirus update. 15th annual International Papillomavirus Workshop,
      Gold Coast Australia, 6 December 1996.

PMID- 9180136
TI  - Mutations of O6-methylguanine-DNA methyltransferase gene in esophageal cancer
      tissues from Northern China.
AB  - Epidemiologic studies have implicated the involvement of environmental factors in
      the etiology of esophageal cancer (EC). Our previous data have indicated that EC
      patients and their blood relatives show genomic instability and are deficient in
      repair of DNA damage induced by N-nitroso-compounds and related genotoxic agents.
      Thus, exposure to high levels of N-alkylnitrosamines, which are known animal
      carcinogens and which induce alkyl adducts in DNA, may be causally linked to EC.
      Among the alkyl adducts, O6-alkylguanine was shown to be the critical one related
      to carcinogenic lesions; its repair varies widely in a tissue-specific fashion.
      O6-methylguanine-DNA methyltransferase (MGMT) is responsible for its repair.
      Hence, inactivating mutations in this protein would impair the efficiency of the
      repair process. To screen for possible mutations in the MGMT polypeptide in EC
      patients, we analyzed a highly conserved region of the MGMT gene in 40 EC tissues
      and lymphocytes of 6 high-risk EC family members from high EC areas of Northern
      China by polymerase chain reaction single-strand conformation polymorphism and by
      direct sequencing of PCR products. Ten base substitutions (point mutations)
      within 8 codons of 7 EC samples were identified. However, no germline mutation
      was found in the high EC families studied so far. Concurrent study in 30 pairs of
      fresh EC tissues and their adjacent normal mucosa by Southern blot and Western
      blot analyses showed deletion of the MGMT gene in 2 samples. Thus, the high
      frequency of mutations (7/40) and deletions (2/30) of the MGMT gene may be
      partially responsible for the overall high mutation rate observed in EC tissues.

PMID- 9180137
TI  - Tumor-associated lympho-monocytes from neoplastic effusions are immunologically
      defective in comparison with patient autologous PBMCs but are capable of
      releasing high amounts of various cytokines.
AB  - We studied several in vitro activities of tumor-associated lympho-monocytes
      (TALMs) and the concentrations of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4,
      IL-6, IL-10, tumor necrosis factor (TNF)alpha, interferon (IFN)gamma and soluble
      IL-2 receptor (slL-2R) in neoplastic effusions and in the serum of advanced stage
      cancer patients. Comparisons were made with autologous peripheral blood
      mononuclear cells (PBMCs). Autologous PBMCs were compared with PBMCs from normal
      subjects used as controls. TALMs were collected from 13 peritoneal and 18 pleural
      neoplastic effusions, secondary to primary tumors of different sites. After PHA
      stimulation, concentrations of IL-1alpha, IL-1beta and TNF alpha in culture media
      of TALMs both from peritoneal and pleural effusions were lower than those of
      autologous PBMCs and, similarly, concentrations of IL-4 and IL-10 in culture
      media of TALMs from peritoneal effusions were lower than those of autologous
      PBMCs, whereas concentrations of IL-4 and IL-10 in culture media of TALMs from
      pleural effusions were in the same range as those of autologous PBMCs. On the
      contrary, IL-2, IL-6 and IFN gamma amounts (only from pleural effusions) were
      significantly higher. IL-1alpha, IL-1beta, IL-2, IL-6 and TNF alpha production
      from patient PBMCs was lower than that of control PBMCs, whereas production of IL
      4, IL-10 and IFN gamma was higher than that of control PBMCs. Both in peritoneal
      and in pleural effusions concentrations of IL-1alpha, IL-1beta and IL-4 were not
      different from those measured in autologous serum, whereas those of IL-6, IL-10,
      TNF alpha, IFN gamma and sIL-2R were significantly higher. The amounts of IL-2 in
      pleural effusions were not different from those of autologous serum, but in
      peritoneal effusions they were higher than those of autologous serum. The amounts
      of IL-1alpha, IL-1beta, IL-2, IL-6, TNF alpha and sIL-2R were higher in patient
      than in control sera, whereas those of IL-4, IL-10 and IFN gamma were in the same
      range in patient and in control sera. Cell cycle analysis of cultured TALMs and
      PBMCs (from 3 patients) showed a significant accumulation of TALMs in the non
      cycling G0/G1 cell population compared with autologous PBMCs.

PMID- 9180138
TI  - Expression of interleukin 15 (IL-15) in human rhabdomyosarcoma, osteosarcoma and
      Ewing's sarcoma.
AB  - Interleukin 15 (IL-15) is a recently discovered cytokine that stimulates
      lymphocyte proliferation and migration via a trimeric receptor sharing the beta
      and gamma signal transducing chains with the IL-2 receptor. IL-15 is typically
      produced by normal cells that do not release IL-2, but little information is
      currently available on human tumors. To assess whether human musculo-skeletal
      sarcomas produce IL-15, we analyzed surgical specimens and cell lines obtained
      from rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma. IL-15 mRNA was present
      in 9/9 surgical specimens (3 Ewing's sarcomas, 5 osteosarcomas and 1
      rhabdomyosarcoma). The analysis of a panel of cell lines (7 derived from Ewing's
      sarcoma, 12 from osteosarcoma and 5 from rhabdomyosarcoma) showed that all
      rhabdomyosarcoma and osteosarcoma cell lines expressed IL-15 mRNA at levels
      ranging from low to high, while Ewing's sarcoma cells contained little or no IL
      15 message. ELISA assays showed IL-15 release in a subset of rhabdomyosarcomas
      and osteosarcomas, but not in Ewing's sarcoma. The highest production of IL-15,
      in the picogram/ml range, was found in rhabdomyosarcoma cell lines RH30 and RD.

PMID- 9180139
TI  - Lack of association of cytochrome P450 2E1 genetic polymorphisms with the risk of
      human hepatocellular carcinoma.
AB  - The iso-enzyme pattern of cytochrome P450 was shown to be related to the
      development of chemically induced hepatocellular carcinoma (HCC) in rats, which
      is accelerated by chronic alcohol ingestion. Our study was designed to
      investigate the association of cytochrome P450 2E1 (CYP2E1) genetic polymorphisms
      with the susceptibility to HCC in humans with and without chronic alcohol
      ingestion. We enrolled 171 male patients (108 Korean and 63 Japanese) with HCC
      and 31 age- and sex-matched healthy Korean subjects with no evidence of liver
      disease or cancer in any organ. Genotypes in the 5'-flanking region of the CYP2E1
      gene were determined by restriction fragment length polymorphisms using 2
      endonucleases: Pst I and Rsa I. Allelic frequencies in the CYP2E1 5'-flanking
      region in the Korean control population were 83.5% and 16.5% for allele c1 and
      c2, respectively. The frequencies of genotypes with the c2 allele (c1/c2 and
      c2/c2) were compared with those of genotypes without c2 (c1/c1) among HCC
      patients and controls, according to the pattern of alcohol consumption. There was
      no significant association between HCC risk and genotypes c1/c2 and c2/c2 either
      in all HCC patients or in HCC patients of different ethnic groups. Habitual
      drinkers with HCC, especially among Koreans, were more likely to carry genotype
      c1/c2 and c2/c2 (odds ratio = 3.0) than non-habitual drinkers (odds ratio = 1.2);
      however, the difference was not statistically significant. Even when patients
      were restricted to those without hepatitis B surface antigen and antibodies
      against hepatitis C virus but with a history of chronic alcohol ingestion, there
      was still no increased risk of HCC in those with genotypes c1/c2 and c2/c2. We
      conclude that there is a lack of association of the polymorphisms of CYP2E1 with
      the risk of HCC in humans.

PMID- 9180140
TI  - Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial
      tumors and their tumor-potentiating function.
AB  - The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a
      polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer
      tissues and containing a variable number of tandem 20 amino acid repeat units,
      and the MUC1/Y protein, which lacks this repeat array and, therefore, is not
      polymorphic. Despite their documented importance in signal transduction
      processes, the relative expression of the 2 isoforms in epithelial tumors is
      unknown. Using antibody reagents which recognize different MUC1 domains, the
      expression of these isoforms in malignant epithelial cells has been evaluated. A
      comparison of the amounts of the 2 isoforms revealed preferential expression of
      the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although
      the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma
      epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The
      presence of the MUC1/Y sequence as well as that of an additional tandem-repeat
      array-lacking isoform, designated MUC1/X, were demonstrated by reverse
      transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma
      cells. It has been shown previously that the MUC1 cytoplasmic domain interacts
      with the SH2 domain containing GRB2 protein, which transduces signals to ras, a
      protein which in its activated form can lead to cell transformation. We present
      here data demonstrating that MUC1/Y isoform expression increases the tumorigenic
      potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of
      tumorigenicity is not observed with MUC1/REP expression. Our studies thus
      demonstrate that expression of the MUC1 gene in epithelial tumors can give rise
      to substantial levels of MUC1 proteins devoid of the tandem repeat array, which
      are generated by alternative splicing mechanisms.

PMID- 9180141
TI  - Expression of an Epstein-Barr-virus receptor and Epstein-Barr-virus-dependent
      transformation of human nasopharyngeal epithelial cells.
AB  - The human herpes virus Epstein-Barr (EBV) is clearly associated with African
      Burkitt's lymphoma and the undifferentiated form of nasopharyngeal carcinoma
      (NPC). EBV has been implicated in other types of lymphoma, as well as in some
      human breast cancers. However, its route of entry into epithelial cells is
      incompletely understood. We report here evidence that there is no gene alteration
      in the SCR 1 and 2 exons of EBVR/CR2 in human embryonic nasopharyngeal epithelial
      (HENE) cells and NPC cells and that SCR 1 and 2 mRNA could be detected in HENE
      cells, different differentiated NPC cell lines and well-differentiated NPC
      biopsies. None of 15 cases of poorly differentiated NPC cryosections has SCR 1
      and 2 mRNA. We also provide evidence that transformation of HENE cells results
      from exposure to infectious EBV and that transformation is dependent on the
      presence of phorbol ester. These data suggest that expression of SCR 1 and 2 of
      EBVR/CR2 may be associated with replication of EBV and support the notion of
      direct infection and transformation of human nasopharyngeal epithelial cells
      destined to evolve into the carcinoma by EBV through EBVR/CR2.

PMID- 9180142
TI  - Measurement of free PSA in the diagnosis and staging of prostate cancer.
AB  - The purpose of this study was to analyze the role of total prostate-specific
      antigen (PSA) and free-PSA levels in the diagnosis and clinical staging of
      prostate cancer. We determined total-PSA serum concentration and free-PSA
      percentage in 352 patients, 234 with benign prostatic hyperplasia (BPH) and 118
      with prostate cancer. Clinical stage of patients with prostate cancer was T1 N0
      M0 in 17, T2 N0 M0 in 27, T3-4 N0 M0 in 34 and T1-4 N0-3 M0-1 in 40. Median total
      PSA serum concentration was 3.1 ng/ml in patients with BPH and 26.9 ng/ml in
      patients with prostate cancer, p < 0.0001. Median free-PSA level was 16.7% in
      patients with BPH and 8.1% in patients with prostate cancer, p < 0.0001. A
      cutpoint of 4.0 ng/ml detected 96.6% of the prostate cancer, but the percent rate
      of negative biopsies was 42.1%. For a free-PSA level of 25% in patients with
      total PSA greater than 4.0 ng/ml, the sensitivity was 97.4%, and the decrease in
      negative biopsies was 21%. Median total-PSA serum concentration in patients with
      prostate cancer according to clinical stage was 8.9 ng/ml for T1 N0 M0, 12.9
      ng/ml for T2 N0 M0, 29.9 ng/ml for T3-4 N0 M0 and 317 ng/ml for T1-4 N1-3 M0-1, p
      < 0.001. Median free-PSA levels were 10.1%, 8.1%, 8.4% and 6.1% respectively, p >
      0.05. According to the Gleason score, median total-PSA serum concentration was
      10.6 ng/ml in patients between 2 and 4, 22.3 ng/ml between 5 and 7 and 77.0 ng/ml
      between 8 and 10, p < 0.05. Free PSA levels were 7.7%, 8.7% and 6.6%
      respectively, p > 0.05. Determination of percentage of free PSA appears to be a
      helpful method for enhancing the specificity of total PSA. A cutpoint of 25%
      could detect more than 95% of prostate cancers and avoid 21% of negative biopsies
      in patients with total PSA above 4.0 ng/ml. However, this parameter does not
      provide additional information about the clinical staging of prostate cancer.

PMID- 9180143
TI  - Fatty foods and the risk of lung cancer: a case-control study from Uruguay.
AB  - To examine whether fatty-food consumption modifies lung-cancer risk, a case
      control study involving 377 patients with lung cancer and 377 controls was
      conducted in Uruguay. The study was restricted to men. Dietary patterns were
      assessed in detail using a 64-item food-frequency questionnaire, which allowed
      the calculation of total energy intake. After adjustment for potential
      confounders (body-mass index, family history of lung cancer, total energy intake
      and tobacco smoking), an increase in risk for fatty-food consumption was
      observed. In particular, fried foods (OR, 1.54; 95% CI, 1.01-2.35), dairy
      products (OR, 2.85; 95% CI, 1.73-4.69) and desserts (OR, 2.52; 95% CI, 1.54-4.12)
      were associated with increases in lung-cancer risk and significant dose-response
      patterns. The association with dairy products was more evident for adenocarcinoma
      of the lung (OR, 4.18; 95% CI, 1.87-9.36), whereas increased risks for fried-meat
      and dessert consumption were observed in each cell type. The association with
      fried-meat consumption was more pronounced for current smokers and for heavy
      smokers, whereas dairy products and desserts were associated with risk both in
      current and in past smokers. In conclusion, fat-rich foods and sucrose-rich foods
      were positively associated with an increased risk of lung cancer. Although the
      relationship between fat consumption and lung cancer has been reported, the
      direct association of lung cancer with sucrose-rich foods should be further
      investigated.

PMID- 9180144
TI  - N-ras protein: frequent quantitative and qualitative changes occur in human
      colorectal carcinomas.
AB  - Point mutation and overexpression are recognized mechanisms for ras activation in
      malignancy. However, little information is available on overexpression of N-ras
      protein compared with H- or K-ras proteins, as N-ras-specific antibodies have
      only recently become available. For comparative analyses of ras protein levels,
      we have probed Western blots of extracts from 9 normal human tissues and 55 pairs
      of colorectal carcinoma and matched control mucosa, using monoclonal antibodies
      (MAbs) specific for H-, K- or N-ras proteins. On multi-tissue blots, N-ras
      protein was more highly expressed in colon than in the other human tissues
      analyzed, suggesting a role for N-ras in colorectal function. N-ras protein
      levels in multiple independent extracts of normal colon mucosa were consistently
      higher than either K-ras protein or H-ras protein levels. In 69% of colon
      carcinomas, N-ras protein levels were increased an average of 4.8-fold over
      normal mucosa. Overexpression of K-ras protein was also observed in colon cancers
      but less frequently (13% of cases) than N-ras protein. H-ras protein levels were
      too low for comparative studies. Alterations in N-ras protein mobility, possibly
      reflecting increased post-translational processing, were also detected in 42% of
      colon carcinomas. N-ras protein, typically present as a single 23 kDa band in
      normal mucosa, was expressed in some cancers as a 22 kDa band or as multiple
      bands of 20-23 kDa. Sequencing of N-ras DNA from 6 carcinomas with these
      variations in protein mobility did not reveal mutations in codons 12, 13, 59 or
      61. Thus, frequent quantitative and qualitative changes in N-ras protein
      expression, which do not appear to correlate with the presence of typical N-ras
      point mutations, result in abnormal N-ras protein patterns in human colorectal
      carcinomas.

PMID- 9180145
TI  - Seroprevalences of hepatitis B and C viruses and Helicobacter pylori infection in
      a small, isolated population at high risk of gastric and liver cancer.
AB  - The objective of this study was to examine the seroprevalences of chronic
      infection with hepatitis B and C viruses and Helicobacter pylori in Matzu, a
      group of small islets with 5,566 civilian residents who have extremely high
      mortality from cancers of the stomach and liver. The standardized mortality
      ratios (SMR) of all cancer sites combined, liver cancer and stomach cancer in
      1984-1993 were calculated using the general population in Taiwan as the referent
      (SMR = 100). The SMRs (95% confidence interval) for all cancer sites combined,
      liver cancer and stomach cancer were 160 (131-195), 252 (170-360) and 351 (229
      516), respectively, in Matzu. A health survey was carried out with 1,485 civilian
      residents aged 30 years or more, giving a response rate of 69% among those who
      were eligible. Serum samples were tested for antibodies against Helicobacter
      pylori (anti-HP) by enzyme-linked immunosorbent assay and hepatitis B surface
      antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) by enzyme
      immunoassay. The seroprevalence was 61% for anti-HP, 24.7% for HBsAg and 1.8% for
      anti-HCV in Matzu. While mortality rates of liver and stomach cancers were
      significantly higher in Matzu than in Taiwan, the seroprevalences of anti-HP,
      HBsAg and anti-HCV in Matzu were similar to or even lower than those in Taiwan.
      These findings suggest the existence of risk factors other than microbial agents
      involved in the development of stomach and liver cancers.

PMID- 9180146
TI  - Trends in the incidence of ovarian cancer and borderline tumours in Norway, 1954
      1993.
AB  - Histology-specific long-term trends in the incidence of ovarian cancer and
      borderline tumours in Norway were examined, based on data from the population
      based Cancer Registry of Norway. A total of 14,352 cases of ovarian cancer were
      diagnosed between 1954-1993, of which 94% of the histologically verified ovarian
      cancers were epithelial tumours. The age-adjusted incidence rate rose from 10 per
      100,000 person-years in 1954-1958 to a peak of 14 per 100,000 person-years in
      1984-1988. In women older than 50 years, there was an increasing trend in
      incidence rates during the entire study period. From the cohort perspective, the
      largest increase was observed among women born between 1870-1899. A total of
      2,343 borderline tumours was diagnosed between 1970-1993. The age-adjusted
      incidence rate has increased since 1970, reaching 4.8 per 100,000 person-years in
      1989-1993.

PMID- 9180147
TI  - Expression of drug resistance proteins in breast cancer, in relation to
      chemotherapy.
AB  - Drug resistance plays an important role in chemotherapy failure in breast cancer.
      We studied the expression of MDR1, MRP, LRP, DNA topoisomerases, p53 and Ki-67 in
      different groups of breast cancer patients in relation to chemotherapy. Tissues
      from 6 normal breasts and 20 primary operable, 40 locally advanced and 10
      anthracycline-resistant metastatic breast cancers were assessed. Sequential
      samples of the same patient were available from 17 patients with locally advanced
      breast cancer undergoing neo-adjuvant chemotherapy and in 7 metastatic patients
      undergoing paclitaxel treatment. Protein expression was investigated by
      immunohistochemistry. Significantly higher protein expression was observed for
      Pgp, Ki-67 and p53 in the locally advanced breast cancers than in primary
      operable breast cancers. No other significant differences in protein expression
      were found among the 3 breast cancer groups. Expression of none of the markers
      that could be assessed (Pgp, MRP, LRP, p53 and Ki-67) in locally advanced breast
      cancer had predictive value for pathological response. Interestingly, after
      chemotherapy a significant decrease in percentage of Ki-67 positive tumor cells
      was observed, whereas the other markers did not vary substantially. Furthermore,
      considering all breast cancer samples, a cumulative dose of doxorubicin >400
      mg/m2 inversely correlated with Ki-67 positivity. However, 2 patients with a
      pathological complete remission had only 5-10% Ki67-positive tumor cells before
      chemotherapy, indicating that Ki67 negativity itself is not responsible for
      chemoresistance. In conclusion, none of the known proteins related to multidrug
      resistance predicted response to chemotherapy in breast cancer, and resistant
      clones left behind generally had a low proliferation rate.

PMID- 9180148
TI  - p53 mutations in relation to human papillomavirus type 16 infection in squamous
      cell carcinomas of the head and neck.
AB  - The relationship between human papillomavirus (HPV) type 16 infection and p53
      gene mutations was investigated in squamous cell carcinomas of the head and neck
      (SCCHN). HPV was detected by general primer-mediated and type-specific PCR.
      Alterations in the p53 gene were investigated using single-strand conformation
      polymorphism and sequence analysis in 27 SCCHN, of which 12 were HPV 16-positive
      and 15 were HPV-negative. Mutations were detected in 2/12 (16.7%) HPV 16-positive
      and 7/15 (46.7%) HPV-negative tumours; this difference was not statistically
      significant. The predominant mutations were deletions and C --> T transitions; G 
      -> T transversions were found in only 2 tumours. Our results indicate that the
      presence of HPV 16 and p53 mutations is not mutually exclusive and detection of a
      p53 mutation does not exclude a potential role for HPV 16 in the pathogenesis of
      a subset of SCCHN.

PMID- 9180149
TI  - Family history and the risk of breast cancer: a systematic review and meta
      analysis.
AB  - An increased risk of breast cancer in women with a family history of breast
      cancer has been demonstrated by many studies using a variety of study designs.
      However, the extent of this risk varies according to the nature of the family
      history (type of relative affected, age at which relative developed breast cancer
      and number of relatives affected) and may also vary according to age of the
      individual. The aim of our study was to identify all the published studies which
      have quantified the risk of breast cancer associated with a family history of the
      disease, and to summarise the evidence from these studies, with particular
      emphasis on age-specific risks according to subject and relative age. Seventy
      four published studies were identified. The pooled estimate of relative risk (RR)
      associated with various family histories was as follows: any relative, RR = 1.9
      (95% CI, 1.7-2.0); a first-degree relative, RR = 2.1 (CI = 2.0, 2.2); mother, RR
      = 2.0 (CI = 1.8, 2.1); sister, RR = 2.3 (CI = 2.1, 2.4); daughter, RR = 1.8 (CI =
      1.6, 2.0); mother and sister, RR = 3.6 (CI = 2.5, 5.0); and a second-degree
      relative, RR = 1.5 (CI = 1.4, 1.6). Risks were increased in subjects under age 50
      and when the relative had been diagnosed before age 50.

PMID- 9180150
TI  - Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional
      injection into glioblastomas.
AB  - We analyzed the biodistribution of the 111In-labelled murine anti-tenascin-C MAb
      BC-2 after intralesional injection in 15 glioblastoma patients. The activated
      ligand DTPA was conjugated via the isothiocyanato-benzyl group onto BC-2.
      Conjugates were labelled with 111In, displaying immunoreactivity greater than 90%
      and labelling efficiency of 99 +/- 1%. In contrast to i.v. injections, excellent
      tumor uptake was obtained by direct intralesional injection of conjugates that
      showed only slow systemic release. In serum, conjugates were found to be intact;
      in urine, only low-molecular-weight decay products were detected. In 8 patients,
      outflow from the site of injection into systemic circulation was low; daily
      activity in the serum and urine was found to be below 2% of the total injected
      radioactivity; most of the injected activity was retained within the tumor,
      resulting in effective half-lives of 58 +/- 5 hr. In contrast, higher outflow up
      to 10% of regionally injected 111In-DTPA-BC-2 MAb into systemic circulation
      resulted in considerable shortening of the effective half-lives to 20 to 40 hr in
      7 patients. This outflow was found to correlate with tumor size and blood/brain
      barrier disruption. In one patient, HPLC analysis of tumor cyst fluid 3 and 6
      days after intralesional injection revealed conjugates to be intact and allowed
      the estimate of about 70% of the total injected 111In-DTPA-BC-2 to be confined to
      tumor tissue. We conclude that different outflow patterns can be observed
      following locoregional injection of 111In-DTPA-BC-2, leading to considerable
      variations in the effective half-lives of isotopes within the tumor, requiring
      adjustment of the radiation dose in therapeutic trials.

PMID- 9180151
TI  - Decreased drug accumulation in a mitoxantrone-resistant gastric carcinoma cell
      line in the absence of P-glycoprotein.
AB  - An established gastric-carcinoma cell line, EPG85-257P, is extremely sensitive to
      mitoxantrone (IC50, 0.12 ng/ml). Stepwise selection with mitoxantrone for 3 years
      resulted in a cell line (EPG85-257RN) that is 7,056-fold resistant to
      mitoxantrone (IC50, 846 ng/ml) and displays cross-resistance to the
      topoisomerase(topo)-II poisons ametantrone (411x), etoposide (112x) and
      teniposide (60x) as well as the topo-I poisons 7-ethyl-10-hydroxycamptothecin
      (331x) and topotecan (58x). We now show that this resistance is multifactorial.
      Western blotting revealed a 5-fold decrease in topo-IIalpha polypeptide in the
      mitoxantrone-resistant cells. Immunohistochemistry and Western blotting failed to
      demonstrate P-glycoprotein overexpression. Formation of trapped topo-II-DNA
      complexes in the resistant cells required higher mitoxantrone concentrations than
      in parental cells, even though nuclei isolated from the EPG85-257RN cells formed
      cleavage complexes normally. In agreement with these observations, which suggest
      the possibility of a defect in mitoxantrone accumulation, examination of
      mitoxantrone accumulation in both cell lines by confocal laser microscopy
      revealed that the EPG85-257RN cells accumulate less mitoxantrone at steady state.
      From these results, we propose that mitoxantrone accumulation, along with
      alterations in topo-IIalpha expression, contribute to the resistance to
      mitoxantrone observed in these cells.

PMID- 9180152
TI  - Role of sinusoidal heparan sulfate proteoglycan in liver metastasis formation.
AB  - Previous studies have indicated that the predominant sites of tumor cell
      extravasation in the liver are the sinusoidal vessels, where tumor cells contact
      the sinusoidal endothelium and the subendothelial extracellular matrix containing
      the basic components of the basement membrane. We studied the role of sinusoidal
      extracellular matrix in metastatsis formation by 3LL-HH murine tumor cells
      selected for their preferential liver colonization. 3LL-HH tumor cells did not
      efficiently adhere to cryosections of the liver, but they recognized the
      sinusoids and vessel walls. Pre-treatment of the mice with polyclonal anti
      basement membrane antibodies [anti-laminin, anti-fibronectin and anti-heparan
      sulfate proteoglycan (HSPG)] significantly modulated the organ distribution of
      tumor cell colonies following intracardial injection: all 3 antibodies inhibited
      kidney colonization; anti-laminin and anti-fibronectin antibodies inhibited lung
      colonization; and only anti-HSPG antibody inhibited liver colonization. In
      several organs such as the heart, stomach, pancreas and bladder, anti-basement
      membrane antibody treatment did not alter the process of colonization.
      Immunofluorescence studies showed that anti-HSPG antibody recognized the basement
      membranes of sinusoids and blood vessels. Our data suggest a specific involvement
      of sinusoidal HSPG in the liver colonization of 3LL-HH cells.

PMID- 9180153
TI  - Elevated expression of calcium-binding protein p9Ka is associated with increasing
      malignant characteristics of rat prostate carcinoma cells.
AB  - Northern and Western blotting techniques were used to study expression of the
      mRNA and corresponding protein product of the S100-related calcium-binding
      molecule p9Ka in 6 different metastatic cell lines of the Dunning R3327 rat
      prostate cancer model. In cells with the lowest metastatic capability (G cells),
      p9Ka mRNA was barely detectable. In 2 weakly metastatic cell lines (AT-1 and AT
      2), p9Ka transcript amounts were, respectively, 6.29 +/- 0.74 and 5.55 +/- 1.11
      times that detected in the G cells. In 3 highly metastatic cell lines (AT-3, MAT
      LyLu and MAT-Lu), the amounts of p9Ka mRNA were, respectively, 12.85 +/- 2.82,
      13.06 +/- 1.69 and 11.62 +/- 1.81 times that expressed in the G cells. Western
      blot analyses detected no p9Ka protein in the G cells. The amounts of p9Ka
      protein expressed by tumour cells of intermediate metastatic capability (AT-1 and
      AT-2) were 3.4 +/- 1.3 microg and 3.3 +/- 1.4 microg, respectively, per 1 x 10(6)
      cells. The amounts of p9Ka protein expressed by the tumour cells of highest
      metastatic capability (AT-3, MAT-LyLu and MAT-Lu) were 8.3 +/- 1.1 microg, 8.7 +/
      1.6 microg and 9.6 +/- 1.7 microg, respectively, per 1 x 10(6) cells. Our data
      reveal a direct association between the elevated expression of mRNA and the p9Ka
      protein amounts and the increased metastatic capability of individual prostatic
      cancer cell lines. We suggest that calcium-binding protein p9Ka may play an
      important role in the metastatic behaviour of rat prostate cancer.

PMID- 9180154
TI  - Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric
      cancer xenotransplanted into nude mice.
AB  - The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver
      metastasis and peritoneal dissemination of gastric cancer was investigated by
      means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2
      and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary
      tumors after orthotopic transplantation of both xenografts when given at a dose
      of 30 mg/kg on alternate days from day 7 after transplantation (early treatment).
      However, growth of the MT-2 primary tumor was not inhibited by administration
      from day 14 after transplantation (late treatment). Liver metastasis was
      prevented significantly by early treatment of TNP-470. In particular, early
      treatment of MT-2 completely inhibited the development of macroscopic foci in the
      liver and was significantly more effective than late treatment. Peritoneal
      dissemination also was inhibited. Thus, TNP-470 was revealed to have strong
      inhibitory activity not only on primary tumors and liver metastases but also
      against peritoneal dissemination. These results suggest that this agent may
      provide a new approach to the treatment of gastric cancer.

PMID- 9180155
TI  - Isolation and characterization of ovarian cancer antigen CA 125 using a new
      monoclonal antibody (VK-8): identification as a mucin-type molecule.
AB  - A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer
      antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by
      affinity chromatography. The biochemical properties of the purified antigen are
      characteristic of a mucin-type glycoprotein: (1) the molecule is highly
      glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N
      acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and
      proline, (3) many of the serine and threonine residues are glycosylated, (4) the
      glycan chains are almost entirely O-linked, with core 2 [Galbeta1 -->
      3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry
      fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. The
      antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in
      urea, but was degraded by proteolytic enzymes to smaller fragments that no longer
      reacted with the antibody. Although this result, and other immunochemical data,
      indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect
      epitopes on the protein portion of the molecule, the involvement of carbohydrate
      cannot be ruled out. Further insight into the structure and function of the CA125
      antigen will come from cloning the gene coding for the peptide backbone, and from
      more detailed carbohydrate structural analysis.

PMID- 9180156
TI  - Effects of bacillus Calmette-Guerin and interferon-alpha-2B on human bladder
      cancer in vitro.
AB  - The cytolytic and anti-proliferative effects of bacillus Calmette-Guerin (BCG)
      and/or interferon-alpha-2b (IFN-alpha-2b) on 5 human bladder carcinoma cell
      lines, RT4, RT112, MGH, SD and J82, were determined. The cell lines showed
      different sensitivities to BCG and IFN-alpha-2b. BCG had direct dose-dependent
      cytolytic and anti-proliferative effects on MGH, J82 and SD (grade 3 cell lines),
      whereas RT4 and RT112 (grades 1 and 2, respectively) were less sensitive.
      Surprisingly, higher concentrations of BCG enhanced cell growth of RT4. IFN-alpha
      2b also had cytolytic and anti-proliferative effects on all 5 cell lines. Thus,
      the RT4 and RT112 cell lines that were not sensitive to BCG were highly sensitive
      to IFN-alpha-2b. A combination of BCG and IFN-alpha-2b had additive anti
      proliferative effects on MGH, J82 and RT112. Interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) production by these 5 cell lines was measured
      after stimulation with BCG and/or IFN-alpha-2b, by ELISA immunoassays. Production
      of IL-6 and TNF-alpha was significantly increased in MGH and J82 cell lines by
      the combination of BCG and IFN alpha-2b. The enhanced cytolytic and anti
      proliferative effects of the combination of BCG and IFN-alpha-2b may be related
      to the induction of cytokines.

PMID- 9180157
TI  - A function in apoptosis other than transactivation inherent in the NH2-terminal
      domain of p53.
AB  - p53-mediated programmed cell death (PMCD) often requires an intact
      transactivation domain of the p53 tumor suppressor and is therefore usually
      interpreted to rely upon the transactivation of genes. As a notable exception,
      murine GHFT1 cells have been documented to perish in a p53-dependent manner even
      in the presence of transcription inhibitor actinomycin D (Act D) and have since
      served as one model system for transactivation-independent apoptosis. We report
      here that p53 transactivation domain mutant Q22,S23 nonetheless fails to mediate
      apoptosis in these cells as efficiently as wild-type p53. This suggests that some
      function of the NH2-terminal domain other than the transactivation of genes
      supports PMCD of GHFT1 cells. To substantiate this suggestion, we employed a p53
      whose transactivation domain had been replaced with the one of VP16, which acts
      through the same elements of the basal transcription machinery. Although the
      hybrid was fully competent for transactivation, it was impaired for the mediation
      of apoptosis to the same extent as mutant Q22,S23. Thus, a function of the
      transactivation domain other than the binding to the transcription co-activators
      hTAF(II)31 and 70 is required for the efficient induction of apoptosis in GHFT1
      cells.

PMID- 9180158
TI  - Co-expression of urokinase-type plasminogen activator and its receptor in human
      gastric-cancer cell lines correlates with their invasiveness and tumorigenicity.
AB  - The expression of urokinase-type plasminogen activator (u-PA), its receptor (u
      PAR) and metalloproteases activity were analyzed in 4 human gastric-cancer cell
      lines (AGS, Hs746T, SNU-1, and SNU-5), in an attempt to relate these activities
      to their invasive potential and tumorigenicity on the modified chorioallantoic
      membranes (CAM) of chick embryos. Only 1 of the 4 cell lines tested, Hs746T,
      expressed both u-PA and u-PAR as well as MMP-2, but not MMP-9. This cell line was
      both tumorigenic and highly invasive (51.3 +/- 13.1%) on a modified CAM. Its
      invasive capacity was comparable with that of a highly malignant human epidermoid
      carcinoma cell line (HEp3), which usually showed 40 to 50% invasiveness. The 3
      other cell lines all produced MMP-2 and MMP-9, but only AGS showed moderate
      invasiveness (24.2 +/- 8.8%). While antibodies to u-PA were significantly
      effective in reducing CAM invasiveness of Hs746T cells by approximately 40%, the
      invasiveness of the t-PA-expressing AGS cell line was not affected by anti-t-PA
      antibodies. These results suggest that when one of the components of the u-PA/u
      PAR system (the enzyme and/or the receptor) is not produced and u-PA/u-PAR
      dependent cell-surface proteolytic activity is thereby diminished, the malignant
      phenotype that can be determined by tumorigenicity and invasion of connective
      tissue on a CAM is compromised. Production of both type-IV collagenases (MMP-2
      and MMP-9) cannot offset this deficiency.

PMID- 9180159
TI  - Release of replication-deficient retroviruses from a packaging cell line:
      interaction with glioma tumor spheroids in vitro.
AB  - The present study describes how various growth conditions affect gene expression
      and virus production from a retroviral packaging cell line (Liz 9), grown as
      monolayers and as multicellular spheroids. In addition, to study the direct
      interaction between packaging cells and tumor tissue of glioma origin, Liz 9
      spheroids were confronted with tumor spheroids derived from a human glioma cell
      line, GaMg. The results show a progressive gene transfer into the tumor tissue,
      with 9% transfection efficacy after 5 days of co-culture. In comparison, no gene
      transfer was observed when the Liz 9 spheroids were confronted with normal brain
      cell aggregates. The Liz 9 spheroids established from early-passage cultures
      (passages 7-14) showed limited growth during 28 days, whereas those initiated
      from late-passage monolayer cultures (passages 39-49) showed extensive growth.
      Flow-cytometric DNA profiles of monolayers and of spheroids indicated no
      difference in cell-cycle distribution or ploidy between early and late passages.
      A cell-viability assay using scanning confocal microscopy revealed mostly viable
      cells in the Liz 9 spheroids, with only a few dead cells scattered within the
      structures. The lacZ-gene expression was maintained in early- and in late-passage
      cultures. In comparison, in Liz 9 early-passage monolayers, the virus titer was
      3.1 x 10(4) +/- 0.4 x 10(4) CFU/ml, whereas no virus titer was found in late
      passage cultures. The virus titer from the Liz 9 spheroids was found to be
      between 10(3) and 10(4) CFU/ml. It is concluded that the virus production from
      packaging cells may vary, depending on passage number and tissue-culture
      conditions. In the present study, this is demonstrated by a complete loss in
      virus titer during prolonged culture of packaging cells. In addition, the 3
      dimensional confrontation system described allows direct visualization of how
      packaging cells interact with tumor tissue. Thus, the co-culture system
      represents a model for studying the efficiency of packaging cells in transfecting
      heterogeneous tumor tissue in vitro.

PMID- 9180160
TI  - A phospholipase D and protein kinase C inhibitor blocks the spreading of murine
      mammary adenocarcinoma cells altering f-actin and beta1-integrin point contact
      distribution.
AB  - Spreading is a critical process involved in motility and growth of tumor cells
      during the metastatic cascade. Focal adhesion kinase, src-proteins and PKC have
      been reported to participate in the regulation of cytoskeleton organization in
      both normal and transformed cells during spreading. The role of other signaling
      enzymes such as PLD and PAP has not been studied during spreading in tumor cells.
      We now show that the spreading of murine mammary adenocarcinoma LM3 cells was
      significantly reduced by n-butanol, a PLD and PKC inhibitor, with a maximal
      inhibition of 54% (p < 0.001) in both the presence and absence of serum, as
      measured by phase-contrast microscopy. PMA only stimulated cell spreading over
      the control in the absence of serum and n-butanol inhibition was completely
      reversed by PMA treatment in both conditions. PA, the product of PLD activity,
      stimulated LM3 cell spreading and the same effect was observed with
      staurosporine. Spreading was enhanced when cells were seeded on collagen-IV- or
      fibronectin-coated surfaces and n-butanol could inhibit both integrin-derived
      signals. Cell spreading inhibition correlated with the absence of f-actin bundles
      and fewer beta1-integrin point contacts as determined by double
      immunofluorescence microscopy. In addition, n-butanol inhibited the proliferation
      of LM3 cells in the presence of serum (p < 0.01). These results suggest that
      beta1-integrin and f-actin/point contact assembly, involved in spreading and
      proliferation, require the participation of PLD-PKC regulatory pathways in LM3
      cells.

PMID- 9180161
TI  - Enhancement of bFGF export associated with malignant progression of human
      salivary gland cell clones.
AB  - Using 2 in vitro systems in which normal human salivary gland cells can be
      immortalized by transfection with SV40 DNA (NS-SV-DC), and in which a non
      metastasizing human salivary gland adenocarcinoma cell clone (HSGc) can be
      converted to biologically aggressive and metastasizing cancer cells, we analyzed
      the relationship between the expression of basic fibroblast growth factor (bFGF)
      and malignant phenotype in human salivary gland cell clones. By enzyme
      immunoassay, intracellular contents of bFGF were equally detected in all the cell
      clones, while bFGF contained in serum-free conditioned medium of each cell clone
      was different: HSGc and metastasizing cell clones, respectively, released 2- and
      10-fold more bFGF into media than did NS-SV-DC. Immunoblot analysis also revealed
      a similar result as that detected by enzyme immunoassay. By Northern blot
      analysis, bFGF mRNA expression was consistently detected in all the cell clones
      examined. We then quantitated bFGF contents in sera of tumor-bearing mice by
      enzyme immunoassay. Although sera from nude mice bearing an HSGc tumor showed
      significantly higher amounts of bFGF than those of control mice, bFGF
      concentrations in sera gradually decreased after removal of the tumor. For
      metastasizing cell clones, serum concentrations of bFGF were 2.2- to 2.6-fold
      higher than those of HSGc. In addition, bFGF amounts in sera after removal of the
      tumors were significantly higher in mice bearing metastasizing cell clone tumors
      compared with those of HSGc tumor-bearing mice. Our results, therefore, indicate
      that increase in bFGF release occurs along with the progression of human salivary
      gland cancer cells and that serum bFGF may be useful for evaluation of tumor
      presence.

PMID- 9180162
TI  - Prostatic kallikrein hK2, but not prostate-specific antigen (hK3), activates
      single-chain urokinase-type plasminogen activator.
AB  - Our work was undertaken to compare the relative efficiency of 2 purified
      prostatic kallikreins, namely, hK2 and prostate-specific antigen (PSA or hK3), in
      the activation of single-chain urokinase (scuPA). We found that hK2 converts
      scuPA into an active enzyme with an efficiency equal to approximately 1/50 that
      of plasmin. During the activation of scuPA by hK2, two fragments of 33 and 22 kDa
      were generated. The NH2-terminal amino acid sequence of the 33 kDa fragment
      showed that hK2 cleaved scuPA between Lys158 and Ile159. In contrast to a
      previous report by another group, our purified hK3 preparation containing no
      trypsin-like contaminants was totally unable to activate scuPA. Our results show
      that kallikrein hK2 has plasmin-like activity and suggest that it could be the
      initiator of a proteolytic cascade leading to prostatic cancer invasion.

PMID- 9180163
TI  - Reversal activity of cyclosporin A and its metabolites M1, M17 and M21 in
      multidrug-resistant cells.
AB  - Cyclosporin A (CSA) is an effective inhibitor of the P-glycoprotein (P-gp)
      activity and has been shown to modulate multidrug resistance (MDR) in in vitro
      experimental models. During degradation of CSA, the metabolites arising from the
      parental compound reach high levels in the serum of patients, and it is not clear
      whether these metabolites maintain the reversal activity of the parental
      compound, like the metabolites of verapamil. In an in vitro experimental model,
      we compared the reversal activity of CSA and 3 CSA metabolites (M1, M17, and M21)
      in the range of concentrations obtained in whole blood during a clinical trial
      with CSA used as a revertant agent. As experimental model we used LoVo-resistant
      cells. Our in vitro studies indicated that the metabolic hydroxylation and
      demethylation of CSA lead to molecules that greatly differ from the parent drug
      in their reversal activity. In the range of concentration detected in the whole
      blood of the patients (1-3 microM), CSA had a significant reversal activity. It
      decreased the IC50 of antineoplastic drugs involved in MDR (vincristine, taxol,
      doxorubicin and etoposide) but not the IC50 of platinum or methotrexate. CSA
      increased intracellular doxorubicin content and inhibited P-gp 3[H]azidopine
      photolabeling. Conversely, CSA metabolite concentrations superimposable to those
      observed in the patients (0.5-2.2 microM) had no sensitizing effects on the
      cytotoxicity of MDR-related anti-neoplastic drugs, nor did they affect
      3[H]azidopine photolabeling or doxorubicin uptake. This study demonstrates that,
      during degradation of CSA, metabolite derivatives arise that have a very
      different reversal activity from that of the parental compound.

PMID- 9180164
TI  - Isolation from a human MDR lung cell line of multiple clonal subpopulations which
      exhibit significantly different drug resistance.
AB  - The heterogeneous nature of an adriamycin-selected human MDR squamous lung cell
      line, DLKP-A, was investigated by isolating and characterising 9 of its clonal
      subpopulations. The DLKP-A cell line exhibits resistance to the classical MDR
      drugs, overexpresses P-glycoprotein and displays reduced topoisomerase II
      amounts. The clonal cell lines exhibit a wide range of resistance extents, with
      the most resistant clone displaying 9 times the extent of adriamycin resistance
      observed in the least resistant clone. A number of clones exhibit sensitivity to
      the concentration of adriamycin in which the parental cell line was selected,
      possibly indicating cooperation between the more and less resistant cells.
      Detailed analysis of 4 of the clonal subpopulations revealed broadly similar drug
      resistance mechanisms. Alterations in expression of the MDR-associated genes MDR1
      and Topo IIalpha were observed, with no detectable changes in the expression of
      MDR3, MRP, GSTpi, Topo IIbeta, Topo I and CYP1A1 noted. However, each clonal cell
      line displayed a distinct extent of expression of MDR1 and Topo IIalpha and
      further characterisation of the clones indicated that other modes of drug
      resistance may exist in at least one of the cell lines. In particular, 2 of the
      clones (DLKPA6B and DLKPA11B) which have almost identical drug resistance
      profiles appear to have quite different mechanisms of resistance. The clonal
      subpopulations possess individual growth rates, amounts of adriamycin
      accumulation and susceptibility to toxicity-enhancement by MDR-modulating agents.
      It was possible to generate a cell line with a drug toxicity profile similar to
      DLKP-A by mixing some of the clonal subpopulations. Our results provide evidence
      of heterogeneity within an MDR human cell population with respect to resistance
      and expression of MDR-associated genes.

PMID- 9180165
TI  - Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus--large
      scale analysis using a new genotyping method.
AB  - The nucleotide at position 1858 of hepatitis B virus has importance in chronic
      hepatitis B (HB) because a cytosine at nt 1858 effectively prevents virus escape
      through the precore TAG stop codon mutation. The relatedness between nt 1858 and
      genotypes was analyzed using a new genotyping method based on restriction
      fragment length polymorphism (RFLP) analysis of an S gene amplicon. Seventy-three
      gene bank sequences were analyzed by phylogenetic tree construction and RFLP
      prediction. A tree supporting the existence of 6 genotypes (A-F) was obtained,
      with C-1858 found in 9 of 9 A genotypes, 0 of 7 B, 0 of 19 C, 1 of 10 D, 0 of 2
      E, and 3 of 3 F. Serum samples from 187 HB e antigen-positive chronic carriers
      were analyzed: Genotypes in northern Europeans were 60% A, 31% D; in southern
      Europeans and Middle Easterners 96% D; in Africans 53% A, 27% D, 20% E; and in
      East Asians 14% A, 43% B, 43% C. Cytosine at nt 1858 was found in 36 of 44 A, 0
      of 32 B, 8 of 34 C, 0 of 59 D, 0 of 3 E, and 1 of 1 F genotype samples.

PMID- 9180167
TI  - Detection of hepatitis G virus (HGV) RNA: clinical characteristics of acute HGV
      infection.
AB  - The role of hepatitis G virus (HGV) infection in acute non-A-E hepatitis was
      investigated in adults with viral hepatitis. HGV RNA was present in 1 of 28
      patients with non-A-E hepatitis but 9 of 22 with hepatitis C (P < .003). HGV RNA
      positive patients (HGV-infected and HGV-hepatitis C virus [HCV]-coinfected)
      developed light-to-moderate jaundice. Clinical and biochemical features of HGV
      positive and HCV-positive patients and patients with non-A, non-G hepatitis were
      similar. Three patients with HGV-HCV coinfection, tested within 18 months after
      disease onset, have remained HGV RNA-positive but have become HCV RNA-negative.
      Only 1 non-A-E hepatitis patient was confirmed as being infected with HGV alone,
      suggesting that HGV is not the main etiologic agent of non-A-E hepatitis.
      Although HGV RNA was significantly associated with hepatitis C, patients with
      mixed HCV-HGV infections did not demonstrate a more severe course of disease than
      did patients with HCV infection.

PMID- 9180166
TI  - Interferon-alpha treatment induces delayed CD4 proliferative responses to the
      hepatitis C virus nonstructural protein 3 regardless of the outcome of therapy.
AB  - The proliferative responses to a hepatitis C virus (HCV) recombinant
      nonstructural protein 3 (rNS3) were analyzed in 9 patients with chronic HCV
      infection before, during, and after 24 weeks of treatment with interferon-alpha
      (IFN-alpha) alone or in combination with ribavirin. Regardless of the therapy and
      the subsequent outcome, all patients showed an increased rNS3-specific
      proliferative response in peripheral blood mononuclear cells in vitro within 48
      weeks from the start of therapy (P < .01). The proliferating cell phenotype was
      CD4 and was dependent on HLA-DP/DQ/DR class II antigen presentation. rNS3 induced
      in vitro detectable interleukin (IL)-2, IL-10, and IFN-gamma production in some
      patients before or after therapy (or both). No significant differences existed
      between responders and relapsed responders plus nonresponders with respect to the
      NS3-specific CD4 T helper (Th) cell responses. Thus, IFN-alpha therapy induces
      HCV NS3-specific CD4 Th cell proliferation regardless of the outcome of therapy.

PMID- 9180168
TI  - Evaluation of retinal toxicity and efficacy of anti-cytomegalovirus and anti
      herpes simplex virus antiviral phosphorothioate oligonucleotides ISIS 2922 and
      ISIS 4015.
AB  - Retinal toxicity of ISIS 2922 and ISIS 4015, phosphorothioate oligonucleotides
      complementary to human cytomegalovirus (CMV) and herpes simplex virus (HSV) RNA,
      were evaluated. The intravitreal concentration of ISIS 2922 found not to cause
      permanent toxic changes in the rabbit retina was 10 microM and in the pig retina,
      5 microM. The 3 microM concentration was associated with a transient inflammatory
      response, and 1 microM caused no retinal toxicity or inflammation. ISIS 4015
      showed very mild toxicity with no permanent retinal changes and very mild
      inflammation at doses of 10 microM; this dose was effective in ameliorating or
      preventing HSV-1 retinitis when injected 1 day and 1 week prior to virus
      inoculation. These oligonucleotides have a low intraocular therapeutic index.
      Attempts to improve the therapeutic index of these compounds are indicated. Only
      a clinical trial can determine the toxicity profile of ISIS 2922 for the
      treatment of CMV retinitis.

PMID- 9180169
TI  - Immune responses to individual rotavirus proteins following heterologous and
      homologous rotavirus infection in mice.
AB  - Serum and intestinal humoral immune responses to rotavirus proteins VP2, VP4,
      VP6, VP7, NSP2, and NSP4 were quantitatively compared in mice infected with a
      homologous murine rotavirus (EHPw) or a heterologous simian rotavirus (RRV).
      Viral protein-specific antibody responses were measured by an
      immunohistochemistry assay that uses recombinant baculovirus-expressed rotavirus
      proteins as antigens. In serum, IgG responses to VP6 were dominant and comparable
      in both RRV- and EHPw-infected groups, but responses to VP2, VP4, VP7, and NSP2
      were higher in RRV infection. In feces, IgA responses to VP2, VP4, and VP6 were
      higher in EHPw-infected mice, but responses to VP7 and NSP2 were detected only in
      the RRV-infected group. These findings indicate that immune responses to
      homologous and heterologous rotavirus infection vary both quantitatively and
      qualitatively. Differences in humoral responses may play a role in the
      differences in protection induced following homologous or heterologous rotavirus
      infection.

PMID- 9180170
TI  - Epstein-Barr virus and human herpesvirus 8 prevalence in human immunodeficiency
      virus-associated oral mucosal lesions.
AB  - The prevalence of Epstein-Barr virus (EBV) and the recently identified Kaposi's
      sarcoma (KS)-associated herpesvirus (also designated human herpesvirus 8 [HHV-8])
      was determined in oral lesions and oral neoplasms common to persons with human
      immunodeficiency virus (HIV) infection. Oral lesions were examined by polymerase
      chain reaction (PCR) for EBV and HHV-8 DNA and by Southern blot analysis for EBV
      clonality. EBV was detected by Southern blot in hairy leukoplakia lesions, in a
      subset of AIDS-related lymphomas, and in saliva from HIV-positive persons but not
      in pseudohairy leukoplakia lesions, oral aphthous ulcers, or oral KS lesions. EBV
      was detected, however, by PCR in most of the lesions, while HHV-8 was detected
      only in oral KSs. The absence of HHV-8 DNA in both the EBV-associated hairy
      leukoplakia lesions and in the EBV-associated AIDS-related lymphomas strengthens
      the etiologic relationship of EBV to these pathologies and the etiologic role of
      HHV-8 in KS.

PMID- 9180171
TI  - Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain
      reaction and p24 antigen detection after immune complex dissociation in an urban
      community hospital.
AB  - Results of polymerase chain reaction (PCR) and p24 antigen detection after immune
      complex dissociation (p24-ICD) were compared with antibody results after 18
      months of age for human immunodeficiency virus (HIV) diagnosis in 345
      prospectively followed, perinatally exposed infants. Of 59 infected and 286
      uninfected infants tested at 1-6 months of age, sensitivity and specificity were,
      respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was
      done on > or = 2 occasions in the first 6 months of life in 43 infected infants;
      77% had > or = 2 positive results with the same test. Of these infants, 68% had 2
      positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none
      had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results
      could have been diagnosed. HIV status can be determined by PCR by age 6 months in
      most HIV-exposed infants. p24-ICD should not be used alone, because of its lower
      sensitivity, but may be useful in areas without advanced laboratory support.

PMID- 9180172
TI  - Experimental perinatal transmission of human immunodeficiency virus type 1 by
      passage of infected T cells.
AB  - Pediatric AIDS typically follows transmission of human immunodeficiency virus
      type 1 (HIV-1) from infected mothers to their offspring. The possibility that
      infected maternal-origin cells serve as a conveyance for mother-to-child HIV-1
      transmission was investigated in a rabbit infection model. Administration of HIV
      1-infected human T cells to pregnant rabbits was followed by evaluation of
      offspring, from newborn to 1.5 years of age. HIV-1 was detected in 11 of 19
      vaginally delivered offspring born to mothers given infected cells during
      gestation. Interstitial pneumonias or lymphoid organ lesions, similar to those
      seen in human pediatric AIDS, occurred in some offspring. Persistence of inoculum
      cell (HLA)-specific gene sequences in offspring indicated that vertical
      transmission can be effected by T cell-associated virus. These results along with
      features of rabbit biology, including primate-type placentation, short gestation,
      and delivery of litters, suggest that the rabbit model is advantageous for
      studies of perinatal HIV-1 transmission.

PMID- 9180173
TI  - Additive or sequential nucleoside analogue therapy compared with continued
      zidovudine monotherapy in human immunodeficiency virus-infected patients with
      advanced disease does not prolong survival: an observational study.
AB  - To study the effect of sequential or additive use of zalcitabine or didanosine on
      survival in 308 human immunodeficiency virus-infected patients with advanced
      disease treated with zidovudine, an observational study using time-dependent Cox
      proportional hazards models was done. Changing to sequential or additive therapy
      was based on deterioration of a patient's health status, a significant drop in
      CD4 cell count, or intolerance for zidovudine. The median CD4 cell count at
      baseline was 110 x 10(6)/L; 42% of patients had AIDS. The median count before a
      change in therapy was 50 x 10(6)/L. Additive or sequential treatment was
      associated with an increased risk for death (relative hazard, 1.59; 95%
      confidence interval [CI], 1.01-2.49; and 1.58; 95% CI, 1.10-2.37, respectively).
      Adjustment of the models for prognostic factors failed to substantially affect
      this observation. Possibly the lack of benefit in this study is because patients
      switched therapy at advanced stages, whereas the switch may be more effective in
      early disease.

PMID- 9180174
TI  - Rapid disease progression without seroconversion following primary human
      immunodeficiency virus type 1 infection--evidence for highly susceptible human
      hosts.
AB  - A patient is described who rapidly progressed from primary human immunodeficiency
      virus (HIV) type 1 infection to death without seroconversion but with
      consistently high plasma viremia. His asymptomatic sex partner had been HIV-1
      seropositive for >8 years prior to transmission. Analysis of viral sequences from
      these subjects and controls confirmed the transmission event. Although the
      biologic properties of the patient's virus were unremarkable, he had poor
      functional immune responses to HIV and an HLA haplotype associated with rapid
      disease progression. The disparity between immune responses and clinical course
      in this transmission pair, coupled with infection with an unremarkable HIV-1
      isolate, underscores the crucial importance of host factors in HIV-1
      pathogenesis.

PMID- 9180175
TI  - Characterization of a polyclonal cytolytic T lymphocyte response to human
      immunodeficiency virus in persons without clinical progression.
AB  - A total of 82 human immunodeficiency virus (HIV)-1-specific cytolytic T
      lymphocyte (CTL) clones were isolated and characterized from 5 HIV-infected
      subjects, utilizing multiple HLA class I alleles. B62-restricted, HIV-1 gag
      specific CTL clones isolated from a single blood sample from 1 subject used four
      different Vbeta gene rearrangements. Multiple CTL clones could be isolated from
      the same time point directed against HIV-1 gag, nef, and env from 1 subject. A
      prospective analysis resulted in the isolation of CTL clones from 1 subject
      directed against multiple HIV-1 antigens, including the same highly conserved nef
      peptide, over a 1-year period, in the absence of detectable circulating viral
      plasma RNA. These data suggest that in some persons without clinical progression
      and low levels of circulating HIV-1, the CTL response is polyclonal, is directed
      against multiple HIV-1 proteins, including highly conserved peptides within these
      proteins, and is maintained over time.

PMID- 9180176
TI  - Dexamethasone therapy worsens the neuropathology of human immunodeficiency virus
      type 1 encephalitis in SCID mice.
AB  - Human immunodeficiency virus (HIV) dementia is a late complication of viral
      infection. Cognitive dysfunction revolves around the secretion of neurotoxins
      from immunologically competent virus-infected brain macrophages and microglia.
      Such macrophage neurotoxins are inflammatory factors that produce selective
      neuronal dysfunction and ultimately cell death. To evaluate the potential
      efficacy of antiinflammatory therapy for HIV dementia, dexamethasone was
      administered to severe combined immunodeficient mice with HIV-1 encephalitis.
      Mice were given therapeutic doses of dexamethasone before intracerebral
      inoculation with HIV-1-infected human monocytes. Histochemical evaluation showed
      a worsening of neuropathology after treatment, with astrogliosis and increased
      apoptosis of neurons. Laboratory investigation of the mechanisms for the
      dexamethasone effects revealed increased viability of HIV-infected macrophages
      and incomplete suppression of neurotoxic inflammatory secretions. The results
      suggest the need for caution in administering glucocorticoids for treatment of
      HIV encephalitis in humans.

PMID- 9180177
TI  - Genetic and phenotypic analysis of Escherichia coli with enteropathogenic
      characteristics isolated from Seattle children.
AB  - Coliform colonies from children whose stools were submitted for microbiologic
      analysis were studied prospectively to determine the frequency of shedding of
      enteropathogenic Escherichia coli (EPEC). In total, 2225 isolates from 445
      patients were probed with eaeA (encoding intimin) and the EAF (EPEC adherence
      factor) probe, and adherence and actin-aggregating phenotypes were determined.
      Twenty-five patients (5.6%) shed non-O157:H7 eaeA+ EAF- E. coli. Of these 25
      patients, isolates from 5 produced Shiga toxins and from 3 possessed bfpA
      (encoding the bundle-forming pilus) sequences. Non-O157:H7 eaeA+ E. coli from 21
      (84%) of 25 patients adhered locally to and aggregated actin in HeLa cells. Four
      patients shed nonadherent EAF+ eaeA- E. coli. Non-O157:H7 eaeA+ and EAF- isolates
      belonged to diverse electrophoretic types and classical and nonclassical
      enteropathogenic serotypes. EPEC are relatively common in stools submitted for
      analysis in this North American pediatric hospital. Their etiologic role in
      childhood diarrhea warrants elucidation.

PMID- 9180178
TI  - Comparison of enzyme immunoassays for antibodies to Haemophilus ducreyi in a
      community outbreak of chancroid in the United States.
AB  - The performance of two EIAs (adsorption EIA and lipooligosaccharide [LOS] EIA)
      that detect antibodies to Haemophilus ducreyi was evaluated with serum specimens
      obtained from 163 patients (96 with genital ulcer disease [GUD]). Paired serum
      specimens (initial and follow-up) were obtained from 52 of the GUD patients. By
      use of initial serum specimens from 82 GUD patients whose etiologic agents for
      their ulcers had been identified, the adsorption EIA had a sensitivity and
      specificity for chancroid of 53% and 71%, while the LOS EIA had a sensitivity and
      specificity of 48% and 89%, respectively. Sensitivity and specificity of the
      adsorption EIA increased to 78% and 84%, respectively, when the results of follow
      up serum specimens were used to calculate optimal performance. The proportion of
      patients testing positive for H. ducreyi who had anti-H. ducreyi IgG antibodies,
      as determined by adsorption EIA, increased with the duration of infection, thus
      limiting the role of EIAs in the diagnosis of chancroid.

PMID- 9180179
TI  - Antimicrobial resistance in Neisseria gonorrhoeae in the United States, 1988
      1994: the emergence of decreased susceptibility to the fluoroquinolones.
AB  - Antimicrobial susceptibilities of Neisseria gonorrhoeae have been prospectively
      determined in the Gonococcal Isolate Surveillance Project of the Centers for
      Disease Control and Prevention. From 1988 through 1994, susceptibilities were
      determined for 35,263 isolates from 27 clinics. Patients were demographically
      similar to those in nationally reported gonorrhea cases. In 1994, 30.5% of
      isolates had chromosomally or plasmid-mediated resistance to penicillin or
      tetracycline. Penicillin resistance increased from 1988 (8.4%) to 1991 (19.5%)
      and then decreased in 1994 (15.6%). Tetracycline resistance decreased from 1988
      (23.4%) to 1989 (17.3%) and then increased in 1994 (21.7%). Most isolates (99.9%)
      were highly susceptible to broad-spectrum cephalosporins. Isolates with decreased
      susceptibility to ciprofloxacin increased from 1991 (0.4%) to 1994 (1.3%); 4
      isolates were ciprofloxacin-resistant. Ciprofloxacin-resistant strains may not
      respond to therapy with recommended doses of fluoroquinolones, and the clinical
      importance of strains with decreased susceptibility is unknown. The emergence of
      fluoroquinolone resistance in N. gonorrhoeae in the United States threatens the
      future utility of this class of antimicrobials for gonorrhea therapy.

PMID- 9180180
TI  - Contrasting effects of lipopolysaccharides (endotoxins) from oral black-pigmented
      bacteria and Enterobacteriaceae on platelets, a major source of serotonin, and on
      histamine-forming enzyme in mice.
AB  - By measurement of serotonin levels, the translocation of platelets to various
      tissues was examined following intravenous injection of a lipopolysaccharide
      (LPS) into C3H/HeN mice. There was a rapid platelet accumulation (within 5 min
      and particularly in the lung), followed by a slower accumulation in the liver,
      which reached its plateau 3-5 h later. The severity of the anaphylactoid shock
      corresponded well with the magnitude of the rapid response. LPSs from the oral
      black-pigmented bacteria, Porphyromonas gingivalis and Prevotella intermedia,
      were much more potent in inducing the rapid platelet response than were those
      from the Enterobacteriaceae Escherichia coli and Salmonella typhimurium. However,
      LPSs from these Enterobacteriaceae were significantly more potent than those from
      black-pigmented bacteria in inducing the slow platelet response. There was also a
      contrast between their abilities to induce histidine decarboxylase, which forms
      histamine from histidine: LPSs from the Enterobacteriaceae were much more potent
      than those from black-pigmented bacteria.

PMID- 9180181
TI  - Penicillin-resistant Streptococcus pneumoniae in the Netherlands: results of a 1
      year molecular epidemiologic survey.
AB  - The molecular epidemiologic characteristics of penicillin-resistant pneumococci
      in the Netherlands were investigated in 1995. Dutch electronic surveillance data
      showed that 0.7% of all pneumococci were intermediately resistant and 0.4% were
      highly resistant to penicillin. From March 1995 to March 1996, 89 penicillin
      resistant isolates were collected by 39 medical microbiology laboratories. Thirty
      different genotypes were observed by restriction fragment end labeling. Twenty
      one DNA types were unique, whereas 9 distinct genotypes were shared by > or = 2
      isolates. Different serogroups were found within 6 of the 9 genetically identical
      clusters of penicillin-resistant isolates, suggesting that horizontal transfer of
      capsular genes is common. Finally, nosocomial transmission of penicillin
      resistant pneumococci was observed among 21 elderly adults with chronic
      obstructive pulmonary disease. This study demonstrates that multiple clones of
      penicillin-resistant pneumococci have been introduced in the Netherlands, a
      country with a low prevalence of pneumococcal infection. Some clones spread among
      the population in and outside hospitals.

PMID- 9180182
TI  - Immunodominant domains present on the Bordetella pertussis vaccine component
      filamentous hemagglutinin.
AB  - To identify immunologically important domains on filamentous hemagglutinin (FHA),
      a Bordetella pertussis protein included in new acellular pertussis vaccines
      (ACPVs), a series of monoclonal antibodies, sera from infants vaccinated with
      ACPVs or whole cell pertussis vaccine (WCPV), and sera from patients with
      pertussis were analyzed by immunoblots containing FHA fragments and recombinant
      FHA proteins. Immunodominant domains located at the COOH-terminus of FHA (type I
      domain) and near the NH2-terminus (type II domain) were defined by the reactivity
      with monoclonal antibodies. The sera from patients with pertussis and sera from
      infants vaccinated with WCPV or with 6 different investigational ACPVs
      specifically recognized well-defined regions within the type I and type II
      domains. Identification of these prominent immunologic epitopes on FHA should be
      useful for the construction of more well-defined pertussis vaccines and for the
      interpretation of human serologic responses, which may correlate with efficacy of
      pertussis vaccines.

PMID- 9180183
TI  - Seroepidemiology of emerging tickborne infectious diseases in a Northern
      California community.
AB  - A seroprevalence and risk factor study of emerging tickborne infectious diseases
      (Lyme disease, ehrlichiosis, and babesiosis) was conducted among 230 residents of
      a semirural community in Sonoma County, California. Over 50% of residents
      reported finding a tick on themselves in the preceding 12 months. Samples from
      51(23%) residents were seroreactive to antigens from one or more tickborne
      disease agents: 1.4% to Borrelia burgdorferi, 0.4% to Ehrlichia equi, 4.6% to
      Ehrlichia chaffeensis, and 17.8% to the Babesia-like piroplasm WA1. Only 14 (27%)
      of these seroreactive residents reported one or more symptoms compatible with
      these diseases. Seroreactivity was significantly associated with younger age (<16
      years), longer residence in the community (11-20 years), and having had a
      physician's diagnosis of Lyme disease. In northern California, the risk of
      infection with these emerging tickborne diseases, particularly in children, may
      be greater than previously recognized.

PMID- 9180184
TI  - Relationship between nasopharyngeal colonization and the development of otitis
      media in children. Tonawanda/Williamsville Pediatrics.
AB  - Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella
      catarrhalis are the predominant bacteria associated with otitis media. A cohort
      of 306 infants was followed from birth through 12 months to determine frequency
      and duration of colonization and risk of acute otitis media (AOM) and otitis
      media with effusion (OME). M. catarrhalis was the most common bacterium isolated.
      Infants colonized at < or = 3 months of age were at increased risk of AOM and
      OME. Early colonization with M. catarrhalis revealed the greatest risk (relative
      risk [RR] = 1.24), especially for OME (RR = 1.57). There was a strong
      relationship between the frequency of colonization and OM (r = .37, P < .001,)
      for each pathogen. Although S. pneumoniae, nontypeable H. influenzae, and M.
      catarrhalis are part of the normal nasopharyngeal flora during infancy, an
      increased rate of colonization may identify a subpopulation of children that is
      at increased risk of OM.

PMID- 9180185
TI  - Interpretation of restriction fragment length polymorphism analysis of
      Mycobacterium tuberculosis isolates from a state with a large rural population.
AB  - Epidemiologic relatedness of Mycobacterium tuberculosis isolates from Arkansas
      residents diagnosed with tuberculosis in 1992-1993 was assessed using IS6110- and
      pTBN12-based restriction fragment length polymorphism (RFLP) and epidemiologic
      investigation. Patients with isolates having similar IS6110 patterns had medical
      records reviewed and were interviewed to identify epidemiologic links. Complete
      RFLP analyses were obtained for isolates of 235 patients; 78 (33%) matched the
      pattern of > or = 1 other isolate, forming 24 clusters. Epidemiologic connections
      were found for 33 (42%) of 78 patients in 11 clusters. Transmission of M.
      tuberculosis likely occurred many years in the past for 5 patients in 2 clusters.
      Of clusters based only on IS6110 analyses, those with > or = 6 IS6110 copies had
      both a significantly greater proportion of isolates that matched by pTBN12
      analysis and patients with epidemiologic connections, indicating IS6110 patterns
      with few bands lack strain specificity. Secondary RFLP analysis increased
      specificity, but most clustered patients still did not appear to be
      epidemiologically related. RFLP clustering in rural areas may not represent
      recent transmission.

PMID- 9180186
TI  - Prevalence and correlates of antibody to chlamydial heat shock protein in women
      attending sexually transmitted disease clinics and women with confirmed pelvic
      inflammatory disease.
AB  - A cross-sectional study of 306 women was done to correlate antibody to the
      chlamydial hsp60 (Chsp60) with epidemiologic, serologic, and laparoscopic
      findings of women with and without pelvic inflammatory disease (PID). Of the 306
      women, 150 had confirmed PID by laparoscopic (n = 69) or histologic (n = 81)
      criteria, and 156 sexually transmitted disease clinic attendees without clinical
      PID did (n = 94) or did not (n = 62) have chlamydia. In multivariate analyses,
      Chsp60 antibody was independently associated with confirmed PID, age > 20 years,
      nonwhite race, > 10 lifetime sex partners, current oral contraceptive use, and
      IgG antibody titers; it was not associated with a positive Chlamydia trachomatis
      culture. Among the 69 women with laparoscopic evidence of PID, the highest level
      of Chsp60 antibody (optical density > 1.0) was found in 8 (80%) of 10 women with
      occluded tubes, compared with 11 (19%) of 58 with patent tubes (P < .001). We
      conclude that antibody to Chsp60 was significantly correlated with risk factors
      for PID, confirmed PID, and occluded fallopian tubes but not with acute C.
      trachomatis infection without PID.

PMID- 9180187
TI  - Epidemiology of Aspergillus infections in a large cohort of patients undergoing
      bone marrow transplantation.
AB  - To investigate the incidence, risk factors, and outcome of Aspergillus infections
      among marrow transplant recipients, records from 2496 patients were reviewed, and
      214 patients had Aspergillus organisms identified. Of these, 158 had invasive
      aspergillosis, 44 were colonized, and 12 had contaminated cultures. The incidence
      of invasive aspergillosis increased from 5.7% to 11.2% during the study. The
      onset of infection was bimodal, peaking 16 and 96 days after transplant. For
      patients within 40 days after transplant, underlying disease, donor type, season,
      and transplant outside of laminar air flow rooms were associated with significant
      risk for invasive aspergillosis. For patients >40 days after transplant, age,
      underlying disease, donor type, graft-versus-host disease, neutropenia, and
      corticosteroid use were associated with increased risk of aspergillosis. Only 31%
      of infected patients were neutropenic at the time of diagnosis. The risk factors
      for aspergillosis depend on the time after marrow transplant and include both
      host and environmental characteristics.

PMID- 9180188
TI  - Iron overload alters innate and T helper cell responses to Candida albicans in
      mice.
AB  - The effect of iron overload on susceptibility of mice to Candida albicans
      infection and on the type of T helper (Th) immunity elicited was investigated.
      Iron overload greatly increased susceptibility to disseminated infection with low
      virulence C. albicans cells of exogenous origin. The candidacidal activity and
      the ability to release nitric oxide and bioactive interleukin (IL)-12 were
      greatly impaired in neutrophils and macrophages from infected mice. CD4 T cells
      from spleens of iron-overloaded mice were found to produce high levels of IL-4
      and IL-10 and low levels of interferon-gamma. Treatment of iron-overloaded mice
      with the iron chelator, deferoxamine, resulted in the cure of mice from
      infection, restored the antifungal effector and immunomodulatory functions of the
      phagocytic cells, and allowed the occurrence of CD4 Th1 protective antifungal
      responses. These data indicate that iron overload may negatively affect CD4 Th1
      development in mice with candidiasis, a function efficiently restored by therapy
      with deferoxamine.

PMID- 9180189
TI  - Endogenous interleukin-12 regulates acquired resistance in experimental visceral
      leishmaniasis.
AB  - Treatment with interleukin-12 (IL-12) induces leishmanicidal activity in
      experimental Leishmania donovani infection; therefore, BALB/c mice were injected
      with anti-IL-12 antibody to define the role of endogenous IL-12 in acquired
      resistance in this disseminated intracellular infection. Anti-IL-12
      administration started 1 day after infection and given for 4 weeks abolished
      control of visceral parasite replication and in parallel suppressed endogenous
      interferon-gamma production and tissue granuloma assembly. Early (during week 1
      only) and delayed treatment (during weeks 2-4 only) with anti-IL-12 also
      exacerbated visceral infection at week 4. These results point to a central role
      for endogenous IL-12 in acquired resistance to intracellular L. donovani and
      suggest that IL-12 is active in the cell-mediated immune response beyond the
      initial stage of host-parasite interaction.

PMID- 9180190
TI  - Increased c-fos expression in the brain during experimental murine cerebral
      malaria: possible association with neurologic complications.
AB  - Cerebral expression of c-fos protein was studied by immunocytochemistry in murine
      cerebral malaria (CM) and malaria without cerebral involvement (non-CM). c-fos
      expression, low in the brains of uninfected mice, increased in frequency,
      intensity, and distribution during the course of fatal CM (e.g., a 70-fold
      increase on day 7 after inoculation). These changes paralleled the timing and
      degree of the neurologic complications and histopathologic changes. Only a slight
      increase in c-fos expression was detectable in non-CM mice on day 7 after
      inoculation. Dexamethasone treatment (days 0 and 1 after inoculation) of the CM
      mice largely prevented the increased cerebral c-fos expression, histopathologic
      changes, cerebral complications, and death. Increased c-fos expression may
      indicate the specific neuronal pathways activated by the immunopathologic process
      of fatal murine CM and could be associated with the behavioral changes and
      neurologic complications in this model.

PMID- 9180191
TI  - Cytomegalovirus monitoring by polymerase chain reaction of whole blood samples
      from patients undergoing autologous bone marrow or peripheral blood progenitor
      cell transplantation.
AB  - Sensitive screening for cytomegalovirus (CMV) by polymerase chain reaction (PCR)
      following autologous bone marrow or peripheral blood progenitor cell
      transplantation has not been evaluated. In a three-center study, 98 autograft
      transplant recipients were prospectively screened for CMV infection by PCR and
      culture techniques. At a median of 20 days (range, 3-28) after transplantation,
      21 (39.6%) of 53 CMV-seronegative patients were PCR positive for CMV, and at a
      median of 17 days (range, 7-84) after transplantation, 19 (42.2%) of 45 CMV
      seropositive patients were PCR positive for CMV. Low-level DNAemia (1-10 fg CMV
      DNA/mL blood) occurred for 1 week in 31 patients but was never associated with
      CMV disease. Of 9 patients who presented with at least two consecutive positive
      PCR results, 1 developed CMV pneumonia. No patients died because of CMV disease.
      Screening for CMV infection by PCR had a negative predictive value of 100% (as
      also observed after allogeneic transplantation), but its positive predictive
      value was significantly lower.

PMID- 9180192
TI  - Immunogenicity of two doses of yeast recombinant hepatitis B vaccine in healthy
      older adults.
AB  - To determine the immunogenicity of two doses of yeast recombinant hepatitis B
      virus (HBV) vaccine containing surface (S) protein, an open-label, multicenter
      trial was conducted in 199 healthy HBV-seronegative adults > or = 40 years old.
      Volunteers were randomly assigned to 1 of 5 groups to receive a total of three 10
      microg doses, at 0, 1, and 6 months, or a total of two doses of 20 microg and 10
      microg, 20 microg and 20 microg, 40 microg and 10 microg, or 40 microg and 20
      microg at 0 and 6 months. The 40-microg/20-microg regimen elicited the highest
      rate of seroprotection (96.2%), with a geometric mean titer of antibody against
      the S protein of 369 mIU/mL, not significantly different from the 536 mIU/mL
      achieved with three doses. These results suggest that a two-dose regimen can
      achieve seroprotection similar to that of the three-dose regimen. Whether a
      shorter interval can be used or a booster dose will be needed later to confer
      durable immunity are unknown.

PMID- 9180193
TI  - Dengue virus inhibits human hematopoietic progenitor growth in vitro.
AB  - Dengue disease, whether it be classical dengue fever (DF), dengue hemorrhagic
      fever (DHF), or dengue shock syndrome (DSS), is frequently associated with
      hematologic disorders. The underlying cause of these abnormalities is unknown. To
      determine if an inhibitory effect on human hematopoietic progenitor growth can be
      observed, normal cord blood mononuclear cells were exposed to low-passaged
      clinical isolates from DF, DHF, and DSS patients and to the prototype strain of
      dengue-3 virus (H-87). In primary methylcellulose cultures, there was no
      inhibition of colony formation. After an initial 8-day liquid culture, inhibition
      was observed with the isolates, but strain H-87 had no effect. Furthermore,
      isolates from patients with DSS showed a more potent inhibitory effect. These
      data represent the first documented study of in vitro impaired progenitor cell
      growth by dengue virus and suggest that this inhibition could be dependent upon
      the isolate tested.

PMID- 9180194
TI  - Transmission of human immunodeficiency virus type 1 resistant to nevirapine and
      zidovudine. Sydney Primary HIV Infection Study Group.
AB  - Human immunodeficiency virus type 1 (HIV-1) resistant to the nonnucleoside
      reverse transcriptase inhibitor nevirapine and to the nucleoside analogue
      zidovudine was transmitted from a homosexual man to his sex partner. The virus
      source patient had commenced combination zidovudine and nevirapine therapy 2.5
      years prior to his partner's primary HIV infection. He received both therapies
      for 7 months, then discontinued nevirapine treatment, continuing to receive
      zidovudine monotherapy for a further 16 months. He had ceased zidovudine therapy
      6 months before the time of his partner's seroconversion. Analysis of major and
      minor isolates obtained from both patients soon after onset of the recipient's
      primary HIV infection illness confirmed that an HIV-1 variant mutant at codons
      70, 98, and 181 of the viral reverse transcriptase was transmitted. This is the
      first documented case of transmission of HIV-1 resistant to two antiretroviral
      compounds.

PMID- 9180195
TI  - Decreased short-term production of tumor necrosis factor-alpha and interleukin
      1beta in human immunodeficiency virus-seropositive subjects.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were
      measured by ELISA in 4.5-h, lipopolysaccharide-stimulated whole blood cultures of
      347 human immunodeficiency virus type 1-infected patients and 107 healthy
      seronegative controls. The production of TNF-alpha was decreased in both AIDS and
      non-AIDS patients, whereas the production of IL-1beta was decreased in AIDS
      patients only. The production of TNF-alpha and IL-1beta was positively affected
      by the concentrations of CD14+ monocytes and CD8+ lymphocytes; however, in
      patients, the concentration of CD4+ lymphocytes and the presence of AIDS had a
      negative effect on cytokine production as determined by multiple linear
      regression analysis. It is concluded that low whole blood cytokine production is
      mainly caused by low numbers of cells, but a functional defect may also exist.

PMID- 9180196
TI  - Molecular analyses of human immunodeficiency virus type 1 V3 region quasispecies
      derived from plasma and peripheral blood mononuclear cells of the first long-term
      nonprogressing mother and child pair.
AB  - Molecular analyses were done for the V3 region quasispecies of human
      immunodeficiency virus type 1 (HIV-1) strains from plasma and peripheral blood
      mononuclear cells of the first HIV-1-infected long-term-nonprogressing mother
      child pair whose members have survived for >13 years with stable CD4 T cell
      counts. There was a predominance of lower V3 loop charge and the absence of
      genotypic changes that are critical in phenotypic determination and tropism
      during HIV-1 infection. The intrahost genetic diversity between HIV-1 strains
      from the mother-child pair compared with HIV-1 strains from slow and rapid
      progressors suggested that a high genetic heterogeneity in HIV-1 strains from
      this HIV-1-infected long-term-nonprogressing mother and child pair was directly
      proportional to the length of their immunocompetent period.

PMID- 9180197
TI  - Antibody response to Arcanobacterium haemolyticum infection in humans.
AB  - Arcanobacterium haemolyticum causes pharyngitis, exanthema, and other infections.
      The evidence of the pathogenicity of A. haemolyticum depends on clinical
      descriptions of culture-positive patients and a comparison of carrier rates of
      patients with pharyngitis and healthy, matched controls. In this investigation,
      the antibody response of the host was studied for the first time, using SDS-PAGE
      and Western blot analyses. Paired acute and convalescent sera showed development
      of antibodies to A. haemolyticum in 7 of 8 patients. The antibodies reacted
      primarily with four distinct cell wall-associated proteins with estimated
      molecular masses of 80, 60, 50, and 30 kDa. Moreover, the reactivity of
      convalescent sera from 19 patients was compared with that of sera from 19
      controls. Antibodies to A. haemolyticum were found in sera from 16 patients and 6
      controls (P < .005); the antibody response of the patients was strong compared
      with that of the controls. These results indicate that A. haemolyticum infection
      induces an antibody response in the host.

PMID- 9180198
TI  - An investigation of geographic clustering of repeat cases of gonorrhea and
      chlamydial infection in San Francisco, 1989-1993: evidence for core groups.
AB  - To determine whether there were core groups of transmitters of gonorrhea and
      chlamydial infection among 14- to 35-year-olds in San Francisco during 1989-1993,
      sociodemographic risk factors for repeat gonorrhea and chlamydial infection were
      examined. During those 5 years, 8613 cases of gonorrhea were reported among males
      and 3893 among females; the proportions with repeat infection were 17.0% and
      19.0%, respectively. There were also 2465 reported cases of chlamydial infection
      among males and 6996 among females; the proportions with repeat infection were
      8.6% and 15.1%, respectively. Multivariate analyses reveal that for males, city
      planning region 5 was an independent risk factor for both repeat gonorrhea
      (relative hazard [RH] = 1.22; 95% confidence interval [CI] = 1.05-1.43) and
      repeat chlamydial infection (RH = 1.78; 95% CI = 1.23-2.57). For females, city
      planning region 4 was an independent risk factor for repeat gonorrhea (RH = 1.50;
      95% CI = 1.12-1.98), and there was no high-risk planning region for repeat
      chlamydial infection. In San Francisco, there appear to be male and female core
      transmitters for gonorrhea but there may not be core transmitters for chlamydial
      infection.

PMID- 9180200
TI  - Etiology of bloody diarrhea in Bolivian children: implications for empiric
      therapy. Bolivian Dysentery Study Group.
AB  - In Bolivia, few data are available to guide empiric therapy for bloody diarrhea.
      A study was conducted between December 1994 and April 1995 to identify organisms
      causing bloody diarrhea in Bolivian children. Rectal swabs from children <5 years
      old with bloody diarrhea were examined for Salmonella, Shigella, and
      Campylobacter organisms; fecal specimens were examined for Entamoeba histolytica.
      A bacterial pathogen was identified in specimens from 55 patients (41%). Shigella
      organisms were found in 39 specimens (29%); 37 isolates (95%) were resistant to
      ampicillin, 35 (90%) to trimethoprim-sulfamethoxazole, and 24 (62%) to
      chloramphenicol, but all were susceptible to nalidixic acid. Only 1 of 133 stool
      specimens contained E. histolytica trophozoites. Multidrug-resistant Shigella
      species are a frequent cause of bloody diarrhea in Bolivian children; E.
      histolytica is uncommon. Clinical predictors described in this study may help
      identify patients most likely to have Shigella infection. Laboratory surveillance
      is essential to monitor antimicrobial resistance and guide empiric treatment.

PMID- 9180202
TI  - Estimation of the annual risk of tuberculosis infection for white men in the
      United States.
AB  - The annual risk of tuberculous infection for white men in the United States was
      estimated from published tuberculin surveys and found to be related to
      tuberculosis incidence as reflected in the annual case rate during the past 3
      decades, with a constant ratio of approximately 150. It is currently estimated to
      be 0.03%/year. The technique developed for this estimation is not complex and
      should be applicable to other segments of the population for which suitable data
      are available.

PMID- 9180199
TI  - Rapid diagnosis of respiratory Chlamydia pneumoniae infection by nested touchdown
      polymerase chain reaction compared with culture and antigen detection by EIA.
AB  - Chlamydia pneumoniae is a common cause of respiratory tract infection and
      community-acquired pneumonia. During an extensive outbreak of C. pneumoniae in
      northern Sweden, 319 respiratory samples from 129 persons were collected. Sputum,
      throat, and nasopharyngeal samples were obtained and analyzed by nested touchdown
      polymerase chain reaction (PCR), EIA, and culture in Hep-2 and McCoy cells.
      Serology was performed by complement fixation and microimmunofluorescence tests.
      By PCR, 30 patients were diagnosed with C. pneumoniae compared with 26 positive
      by EIA and 23 by culture. The finding of C. pneumoniae in the respiratory samples
      was accompanied by serology indicating acute infection in 26 (96%) of 27 patients
      for whom adequate sera were available. Nested PCR was sensitive and reliable for
      diagnosing acute respiratory C. pneumoniae infection. Sputum samples had the
      highest diagnostic efficacy, and the nested type of PCR was superior to one-step
      PCR. EIA and culture were less sensitive than nested PCR.

PMID- 9180201
TI  - Infection of human monocytes with Mycobacterium tuberculosis enhances human
      immunodeficiency virus type 1 replication and transmission to T cells.
AB  - Mycobacterium tuberculosis and human immunodeficiency virus type 1 (HIV-1) are
      virulent intracellular pathogens that invade and multiply within macrophages. The
      effect of M. tuberculosis on HIV-1 infection and replication was analyzed in
      vitro using human monocyte-derived macrophages (MDM) isolated from peripheral
      blood mononuclear cells by countercurrent centrifugal elutriation. Preinfection
      of MDM with M. tuberculosis followed by HIV-1 infection resulted in an increase
      in p24 release, reverse transcriptase activity, and infective virus production.
      In contrast, no increase in HIV-1 production was observed when MDM were infected
      with Mycobacterium avium complex or heat-killed M. tuberculosis. Coinfected MDM
      were potent stimulators of T cell proliferation, while HIV-1-infected MDM failed
      to present exogenous tuberculin to T cells. Furthermore, coinfected MDM showed an
      increased capacity to transmit HIV-1 to activated T cells. These results suggest
      that M. tuberculosis infection can both up-regulate HIV-1 infection and
      replication within MDM and increase the efficiency of virus transmission from
      infected MDM to T cells.

PMID- 9180203
TI  - Alterations to the cell wall of Histoplasma capsulatum yeasts during infection of
      macrophages or epithelial cells.
AB  - Many Histoplasma capsulatum strains have alpha-(1,3)-glucan in their cell walls
      and spontaneously produce variants that lack this polymer. The variants, in
      contrast to the parents, exist in aberrant shapes within macrophages. Here, the
      ultrastructure of the parental and variant cell walls was examined. All yeasts
      had identical electron-lucent, thick walls when grown in broth culture. However,
      ingestion by either macrophages or hamster trachea epithelial (HTE) cells caused
      the walls of variants to become electron-dense, thin, and sinuous. Parental
      strains remained unchanged in macrophages. Within HTE cells inoculated with
      parental strains, some organisms retained a thick wall and alpha-(1,3)-glucan but
      appeared to be degrading. In contrast, apparently intact intracellular yeasts had
      thin, wavy walls lacking alpha-(1,3)-glucan. A microenvironment within HTE cells
      that is unfavorable for the parental phenotype may trigger this ultrastructural
      change, potentially explaining why only variant yeasts are harvested from such
      cultures.

PMID- 9180205
TI  - Nucleotide sequence at position 1081 of the hemagglutinin-neuraminidase gene in
      the mumps virus Urabe vaccine strain.

PMID- 9180204
TI  - Atovaquone and proguanil for the treatment of malaria in Brazil.
AB  - The purpose of this study was to compare an experimental regimen of atovaquone
      plus proguanil with the standard regimen of quinine plus tetracycline for the
      treatment of uncomplicated falciparum malaria. The study was designed as an open,
      randomized study of men presenting with symptoms of uncomplicated malaria and
      thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL).
      Subjects were hospitalized for 28 days to insure medication compliance and to
      rule out the possibility of reinfections. With 77 patients in each group, the
      cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus
      tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever
      clearance times (mean, 19 h) were significantly shorter in the atovaquone plus
      proguanil group, and there were significantly fewer side effects in the
      atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious,
      easily administered, safe regimen for the treatment of uncomplicated, multidrug
      resistant falciparum malaria in Brazil.

PMID- 9180206
TI  - Expression of c-fos in bulbar nuclei involved in cardiovascular control following
      the electrical stimulation of sensorimotor cortex in the rat.
AB  - Previous studies have shown that electrical stimulation of the sensorimotor
      cortex (SMC) induces responses of the autonomic nervous system such as variations
      in heart rate and arterial pressure. Neuroanatomical studies have shown the
      existence of monosynaptic projections from the SMC to the nucleus tractus
      solitarius (NTS), the rostral ventrolateral medulla (RVLM) and the dorsal nucleus
      of the vagus nerve (DNV), which are bulbar nuclei involved in cardiovascular
      control. The aim of the present study was to establish whether there exists a
      functional connectivity between the SMC and these nuclei. Electrical stimulation
      applied to the SMC of 7 rats for 1 h induced the expression of c-fos-protein-like
      immunoreactivity in the nucleus of some neurons in NTS, RVLM and DNV. These data
      support the view that the SMC has functional connections with bulbar neurons
      involved in cardiovascular control.

PMID- 9180207
TI  - Up- and down-regulation of calpain inhibitor polypeptide, calpastatin, in
      postischemic hippocampus.
AB  - Based on our previous observation that transient forebrain ischemia induces
      calpain-catalyzed proteolysis in gerbil hippocampus in a region-specific manner,
      we examined the effect of ischemia on the quantity and localization of the
      endogenous calpain-specific inhibitor protein, calpastatin, in the tissue. Brief
      (5 min) forebrain ischemia followed by reperfusion induced an overall increase of
      calpastatin immunoreactivity in hippocampus, particularly in pyramidal cells, in
      4 h as analyzed by Western blotting and immunohistochemistry. The amount of
      calpastatin, however, decreased to the preischemic level and lower in 24 h to 7
      days due to proteolysis except in CA2 showing continuously elevated calpastatin
      immunoreactivity. Because calpastatin is not only a potent inhibitor but also a
      preferred substrate for calpain and because CA2 neurons are less vulnerable to
      ischemic stress than the adjacent CA1 neurons, these observations imply
      involvement of calpastatin in calpain regulation as a bait substrate and,
      possibly, in neuroprotection under ischemic conditions. Calpastatin may
      participate in the stress responses together with the previously known ischemia
      induced stress proteins such as heat shock proteins.

PMID- 9180208
TI  - Single neuron responses in the monkey anterior cingulate cortex during visual
      discrimination.
AB  - Single neuron activity was recorded from the monkey anterior cingulate cortex
      during operant behavior based on discrimination of rewarding, aversive, and
      neutral objects. Of 550 neurons recorded, 116 responded during the task; 36,
      during visual discrimination; 40, during bar pressing for operant responding. Of
      these, 26 vision-related neurons responded differentially to rewarding, aversive
      and neutral objects, and 11 bar press-related neurons differentiated bar pressing
      to avoid shock from bar pressing to obtain reward. Responses of these neurons
      depended on associative meaning (aversive or rewarding) of the objects since
      these neuronal responses were modulated by the reversal learning. The results
      provide neuronal bases for involvement of the anterior cingulate cortex in
      emotional and motivational processes.

PMID- 9180209
TI  - The effect of electrolytic lesioning of the midbrain prior to amygdala kindling
      in rats.
AB  - Effect of midline electrolytic lesioning in the midbrain was examined in rodent
      amygdala (AM) kindling. During the primary site AM kindling, the lesioned rats (n
      = 5) needed a significantly larger number of stimulations to reach a final stage
      of kindled seizures (stage 5) than the sham operated ones (n = 5). During the
      contralateral secondary site AM kindling, none of the former animals showed a
      positive transfer effect (a reduction in the number of stimulations to reach
      stage 5), whereas all of the latter ones did. The findings indicate that in rats
      the lesioned area of the brainstem participates not only in the development of
      primary site AM kindling but also in the mechanism of transhemispheric positive
      transfer effect.

PMID- 9180210
TI  - Protein tyrosine kinase inhibitors synergize with nerve growth factor in
      embryonic chick sensory neuronal cell survival.
AB  - The survival of developing sensory neurons is dependent upon target-derived
      growth factors, in their absence neurons undergo programmed cell death. The
      molecular mechanisms underpinning neuronal cell survival and death are poorly
      understood. Tyrosine kinases are important signalling proteins that have been
      implicated in both cell survival and death. The aim of this study was to examine
      the effects of tyrosine kinase inhibition on embryonic chick sensory neuronal
      survival using the tyrosine kinase inhibitors, herbimycin, genistein and
      tyrphostin. In low concentrations of nerve growth factor, NGF (100 fg/ml), the
      majority of neurons die, however neuronal survival was significantly potentiated
      in the presence of each of the tyrosine kinase inhibitors, herbimycin (40 ng/ml),
      genistein (2.5 microM) and tyrphostin (8 microM). In the presence of each of
      these inhibitors, sensory neurons exhibited typical phase bright morphology and
      fibre outgrowth was increased. These results demonstrate that the tyrosine kinase
      inhibitors support the survival of neurons in the presence of low concentrations
      of NGF. Herbimycin was used at lower concentrations than previously reported, and
      at this concentration it has been shown to be noncytotoxic in animals. Therefore
      it will be important to determine if herbimycin can be used as a therapeutic
      agent for enhancing nerve regeneration following injury.

PMID- 9180211
TI  - Nitric oxide synthase containing nerves in the cat and dog dental pulp and
      gingiva.
AB  - In a previous study we found that nitric oxide (NO) plays an essential role in
      the hemodynamic regulation of the feline dental pulp. However, no evidence for
      the presence of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)
      containing nerve fibers was found in the rat and cat dental pulps. In the present
      study, we are first to report the presence of a small number of NADPH-d positive
      and/or NO synthase immunoreactive perivascular and solitary varicose axons in the
      dental pulp and abundant number of similar axons in the gingiva of cats and dogs.
      These fibres may travel within the inferior alveolar nerve and might participate
      in sensory (i.e. pain) as well as in autonomic (i.e. regulation of blood flow)
      innervation of the dental pulp and gingiva.

PMID- 9180212
TI  - A bioadaptive approach for experimental pain research in humans using laser
      evoked brain potentials.
AB  - In order to find an experimental approach counteracting habituation in
      experimental pain research using short infrared laser stimulation in humans we
      developed a bioadaptive method based on subject's report on painfulness of
      stimulation (pain report; PR). After determination of the initial relationship
      between the energy of the laser stimulus and the corresponding PRs, the approach
      continuously adjusts the intensity of noxious stimuli so that PR is kept constant
      across time. Each difference between the PR evoked by the actual laser stimulus
      and the desired PR leads to an increase or decrease of the laser output energy
      value for the next stimulation with the desired PR proportional to the PR
      difference as well as to the slope of the initial correlation function between
      laser energy and corresponding PRs. This method has been applied in a study with
      nine volunteers. Results show that the approach leads to a constant PR by
      increasing the laser output energy by 0.01 mJ/s per mm2 on the average.
      Furthermore, an analysis of the laser-evoked brain potentials (LEPs) recorded
      from Cz was performed for the first and second half of stimuli. However, no
      significant changes in latencies or amplitudes of the main LEP components
      recorded at 210 ms (N210) and 350 ms (P350) were found. The method seems to be
      useful for different approaches in experimental and clinical pain research.

PMID- 9180213
TI  - Protein synthesis inhibitor cycloheximide dose-dependently decreases formalin
      induced c-Fos protein and behavioral hyperalgesia in rats.
AB  - We had previously demonstrated that c-fos antisense oligodeoxynucleotides dose
      dependently suppressed formalin-induced c-Fos protein and behavioral
      hyperalgesia. To test whether de novo protein synthesis is required for the
      development of persistent pain after peripheral inflammation, we observed
      formalin-induced spinal c-Fos protein and nociceptive behaviors following
      pretreatment with cycloheximide, a protein synthesis inhibitor. Cycloheximide
      dose-dependently inhibited formalin-induced spinal c-Fos protein and tonic
      nociceptive responses. The possible non-specific effects other than protein
      synthesis inhibition on nociceptive behavior were carefully discussed and
      excluded. These results provide further support to the hypothesis that de novo
      protein synthesis is essential for the development of behavioral hyperalgesia.

PMID- 9180214
TI  - Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of
      diabetic rats.
AB  - We assessed light-induced Fos-immunoreactive cells in the suprachiasmatic nucleus
      of diabetic rats. The number of Fos-immunoreactive cells significantly decreased
      in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats as compared with
      control Long-Evans Tokushima Otsuka (LETO) rats. In contrast there was no
      decrease in the number of Fos-immunoreactive cells in young OLETF rats which have
      not yet developed diabetes. Two months after the administration of streptozotocin
      (STZ) to Wistar rats, the number of Fos-immunoreactive cells significantly
      decreased, although 1 week after the administration of STZ, the number had not
      yet changed in these STZ-induced diabetic rats. These results suggest that
      chronic diabetic (hyperglycemic) conditions may affect the light entraining
      responses in the suprachiasmatic nucleus (SCN).

PMID- 9180215
TI  - InsP3-induced Ca2+ release in dorsal root ganglion neurones.
AB  - The intracellular calcium signalling was studied on subpopulation of freshly
      isolated adult mouse dorsal root ganglia (DRG) neurones with large somatas (30-45
      microns in diameter). The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured
      using indo-1 based microfluorimetry. The extracellular application of ATP (100
      microM) triggered both inward current and [Ca2+]i elevation. Removal of
      extracellular Ca2+ had no effect on both ATP-induced current and [Ca2+]i
      transient. The ATP-induced Ca2+ elevation was inhibited by intracellular
      perfusion of DRG neurones with 20 microM heparin, or by cells incubation with
      thapsigargin or ryanodine. We conclude that mouse proprioceptive sensory neurones
      are endowed with Ca2+-impermeable ionotropic P2X purinoreceptors and metabotropic
      P2Y purinoreceptors, which, by means of phospholipase C-driven inositol
      trisphosphate (InsP3) production, trigger the InsP3-induced Ca2+ release from
      intracellular stores.

PMID- 9180216
TI  - Nitric oxide is not involved in vascular nociception of noxious physical stimuli
      in humans.
AB  - We tested the hypothesis that nitric oxide (NO) is involved in vascular
      nociception of physical stimuli in humans. Vascularly isolated hand vein segments
      of six healthy volunteers were pretreated with the NO synthase inhibitor, N(G)
      nitro-L-arginine methyl ester (L-NAME; 10(-7)-10(-4) M) and repeatedly subjected
      to noxious thermal (2 degrees C, 52 degrees C) or mechanical stimuli (balloon
      distention) and, for control, to the endogenous algetic bradykinin (10(-6) M). L
      NAME prevented in a concentration-related manner the algesic action of
      bradykinin, but had no effect on pain evoked by heat, cold, or stretch. NO is
      therefore not a general chemical link in nociception.

PMID- 9180217
TI  - Biosynthesis of carnosine in primary cultures of rat olfactory bulb.
AB  - Primary cultures of glia cells obtained from adult rat olfactory bulb synthesize
      carnosine (beta-alanyl histidine). The rate of synthesis increases the older the
      culture is and is enhanced by the addition of dibutyrylcyclic-AMP (dBcAMP) to the
      medium. Millimolar concentrations of this agent intensify galactocerebroside
      (GalC) staining compared to control cultures. Removal of GalC positive cells
      through antibody and complement cell killing decreases carnosine synthesis to a
      minimum. Cultures prepared from olfactory bulb of new-born rats contain neuron
      specific enolase (NSE) positive neurons and GalC positive ensheathing cells. Such
      cultures produce carnosine. When switched to nerve growth factor (NGF) depleted
      medium containing dBcAMP the share of neurons in the culture decreases
      drastically with time and concomitantly an increase of the relative rate of
      carnosine synthesis is observed. After 1 week in such medium the cultures contain
      almost no NSE positive cells. Virtually all cells express glial fibrillary acidic
      protein (GFAP) and are GalC positive. These data suggest that carnosine is
      synthesized by the ensheathing cells of the olfactory bulb and not by olfactory
      neurons.

PMID- 9180218
TI  - Codistribution of the dopamine D3 receptor and glucocorticoid receptor mRNAs
      during striatal prenatal development in the rat.
AB  - Glucocorticoids and dopamine (DA) may affect brain development and permanently
      programme central nervous system (CNS) responses. The ontogeny of the striatal
      glucocorticoid receptor (GR) mRNA and of DA D1, D2 and D3 receptor subtype mRNAs
      were, therefore, studied by means of in situ hybridization techniques. The
      expression of GR and the dopamine D3 receptor mRNAs but not of DA D1 and D2
      receptor subtype mRNAs were observed in the striatal neuroepithelium during all
      prenatal stages studied (E14.5-E20.5). These results suggest that GR may directly
      influence striatal developmental processes, possibly involving the dopamine D3
      receptor.

PMID- 9180220
TI  - Increase of urocortin-like immunoreactivity in the rat hypothalamo
      neurohypophysial system after salt loading and hypophysectomy.
AB  - The effect of chronic salt loading on urocortin-like immunoreactivity (Ucn-IR)
      was investigated in the rat hypothalamo-neurohypophysial system. In control rats
      a few Ucn-IR neurons were observed scattered throughout the supraoptic nucleus
      (SON) and few in the paraventricular nucleus (PVN). A small number of Ucn-IR
      fibers were observed scattered in the median eminence (ME) and the posterior
      pituitary. However, after 5 days of chronic administration of 2% saline, a marked
      increase in the number of Ucn-IR perikarya and fibers was observed in the PVN and
      the SON. Additionally, Ucn-IR varicosities and fibers were found in the internal
      zone of the ME and in the posterior pituitary. To confirm the findings and
      examine the possible involvement of anterior pituitary function in synthesis of
      Ucn, surgical hypophysectomized rats were used. Five days after hypophysectomy, a
      marked increase in Ucn-IR was observed in the PVN, the SON, and both the internal
      and the external zone of the ME. These results suggest that Ucn in the
      hypothalamo-neurohypophysial system may be involved in the regulation of salt
      balance, and possibly in the stimulation of ACTH release from the anterior
      pituitary.

PMID- 9180219
TI  - T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not
      responsible for sporadic late-onset Alzheimer's disease in Japanese population.
AB  - To investigate whether presenilin 1 (PS1) gene, a major causative gene of
      familial early-onset Alzheimer's disease (AD), also contributes to the etiology
      of sporadic AD, we evaluated associations between Japanese AD and polymorphisms
      located at 14q24.3. While the D14S43 and FOS loci showed no association with
      either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele
      was associated with the G allele of the T/G polymorphism located at intron 9 of
      the PS1 gene (P = 0.016). Considering another study showing a positive
      association between AD and the T allele, this polymorphism is associated with,
      but not responsible for sporadic late-onset Alzheimer's disease.

PMID- 9180221
TI  - Induction of Fos-like immunoreactivity in the lower brainstem and the spinal cord
      of the rat by intraperitoneal administration of an endogenous satiety substance,
      2-buten-4-olide.
AB  - Induction of Fos in neurons by intraperitoneal injection of 2-buten-4-olide (2
      B40), an endogenous satiety substance, was studied immunohistochemically in the
      brainstem and spinal cord of the rat. Rats injected intraperitoneally with 2-B40
      (100 mg/kg) were allowed to survive for 2 h before perfusion. Fos-like
      immunoreactivity was observed in neurons of the intermediolateral nucleus,
      ventral reticular formation, lateral reticular nucleus, nucleus of the solitary
      tract, locus coeruleus, lateral parabrachial nucleus and dorsal raphe nucleus, as
      well as in tyrosine hydroxylase-immunoreactive neurons of the cell groups A1, A2,
      A5, A6, A7, C1, C2 and C3.

PMID- 9180222
TI  - Induction of tolerance and mossy fibre neuropeptide-Y expression in the
      contralateral hippocampus following a unilateral intrahippocampal kainic acid
      injection in the rat.
AB  - We have previously reported an ectopic expression of neuropeptide-Y (NPY)
      immunoreactivity in mossy fibres (MFs) in the contralateral hippocampus following
      a unilateral intrahippocampal (IH) injection of kainic acid (KA). In the present
      study we report that, in addition to MF NPY expression, unilateral IH KA
      injections also induce tolerance towards a subsequent intracerebroventricular
      (ICV) contralateral KA injection, resulting in a reduction in the number of overt
      seizures and degree of cell loss.

PMID- 9180223
TI  - Alpha1 antichymotrypsin signal peptide polymorphism in sporadic Creutzfeldt-Jakob
      disease.
AB  - In Creutzfeldt-Jakob disease (CJD), a transmissible spongiform encephalopathy,
      the deposition of the pathological prion protein (PrP-res) in the brain of
      affected individuals is the key event that triggers the appearance of the
      disease. Since a polymorphism in the signal peptide of the serine-protease
      inhibitor alpha1 antichymotrypsin (ACT) is one of the factors that may enhance
      amyloid formation, we studied this polymorphism in 63 CJD patients and 103
      control subjects. No difference in allele frequencies and genotype distribution
      was found between CJD cases and controls, nor any difference was found between
      the ACT genotype and the age at onset and disease duration. Interestingly, there
      was a significantly different (P = 0.04) ACT distribution between CJD patients
      and controls in apolipoprotein E (ApoE) E4, and the interaction between ACT and
      ApoE was almost significant (P = 0.053). Further studies on a larger number of
      patients will clarify whether this association can identify a possible risk
      factor for CJD.

PMID- 9180224
TI  - Skeletal and dento-alveolar stability of Le Fort I intrusion osteotomies and
      bimaxillary osteotomies in anterior open bite deformities. A retrospective three
      centre study.
AB  - A sample of 267 patients with maxillary hyperplasia, a Class I or Class II/I
      occlusion and anterior vertical open bites, collected from three different
      institutions, was analysed regarding stability after surgical corrections.
      Skeletal and dento-alveolar stability of the maxilla, and positional changes of
      the mandible and of the incisors were evaluated. All patients underwent Le Fort I
      intrusion osteotomies and in 92 patients segmentation of the maxillae was
      performed. An additional bilateral sagittal split advancement osteotomy was
      performed in 123 patients. Intraosseous wire fixation was used in 153 patients
      and rigid internal fixation in 114 patients. Cephalometric radiographs were
      collected before orthodontic treatment, before surgery, immediately after
      surgery, one year postoperatively and at the latest follow up. The mean follow up
      was 69 months (range 20-210 months). It can be concluded that patients with
      anterior open bites, treated with a Le Fort I osteotomy in one-piece or in multi
      segments, with or without bilateral sagittal split osteotomy, exhibited good
      skeletal stability of the maxilla. Rigid internal fixation produced the best
      maxillary and mandibular stability. The mean overbite at the longest follow up
      was 1.24 mm and a lack of overlap between opposing incisors was present in 19%.
      The overbite did not differ significantly between the different treatment
      procedures, probably due to compensatory movements of the mandibular and
      maxillary incisors.

PMID- 9180225
TI  - A study of mandibular ramus anatomy and its significance to sagittal split
      osteotomy.
AB  - A study is presented, which investigates the position of fusion between the
      buccal and lingual cortical plates. The knowledge of this position will direct
      the placement of horizontal medial osteotomy in modified sagittal split
      osteotomy.

PMID- 9180227
TI  - Rigid fixation with teeth in the line of mandibular fractures.
AB  - The treatment results and the incidence of complications were evaluated
      retrospectively in a group of 68 patients. They all had mandibular fractures with
      a tooth in the line of fracture and were treated using miniplates for fixation.
      The follow up ranged from 1 to 6 years (mean 2.6 years) and 90 fracture sites
      were involved. Results showed that the incidence of complications when the tooth
      was extracted was higher (3/12) than when it was left in place (8/78). With
      regard to both healing of the fracture and fate of the tooth in the line of
      fracture, it is recommended to retain teeth in the line of fracture, unless there
      is an absolute indication for extraction. It is advisable to monitor the vitality
      of teeth adjacent to the fracture line for at least one year.

PMID- 9180228
TI  - Mandibular third molar surgery with primary closure and tube drain.
AB  - The insertion of a small surgical tube drain with primary wound closure (drain
      group) was compared to a simple primary wound closure (no drain group) after
      removal of impacted third molars. Surgery was performed on 23 patients in a
      randomized cross-over fashion. The operation time was found to be significantly
      longer and mouth opening significantly wider in the immediate postoperative
      period in the drain group subjects as compared to the no drain group (P > or =
      0.01). There was no significant difference in the severity of pain between the
      two groups. Facial swelling was found to be significantly less in the drain group
      subjects (P > or = 0.01). The number of patients with wound breakdown, edema, and
      bleeding was found to be less in the drain group than in the no drain group.
      Thus, the postoperative problems, in general, were less in the small surgical
      drain group as compared to the no drain group.

PMID- 9180226
TI  - Ganglion cyst and synovial cyst of the temporomandibular joint. Two case reports.
AB  - Ganglion cysts and synovial cysts are lesions rarely associated with the
      temporomandibular joint. Ganglion cysts arise from myxoid degeneration of the
      connective tissue of the joint capsule, are filled with viscoid fluid or
      gelatinous material, and have a fibrous lining. Synovial cysts also contain
      gelatinous fluid and are lined with cuboidal to somewhat flattened cells
      consistent with a synovial origin. One case of a ganglion cyst and one case of a
      synovial cyst of the temporomandibular joint are presented, and their
      differential diagnosis and management are discussed.

PMID- 9180229
TI  - Osteosarcoma of the jaw bones. Long-term follow up of 48 cases.
AB  - To evaluate the incidence and treatment results of osteosarcoma of the jaw (OSJ)
      in the Netherlands, data from 48 patients with a histologically proven diagnosis
      of osteogenic sarcoma of the maxilla or mandible were retrospectively analysed.
      Patient files, covering the period from 1964 to 1992, were obtained from all
      university hospitals in the Netherlands and the Netherlands Cancer Institute. The
      incidence of OSJ in the Netherlands is estimated to be at least 0.14 per
      1,000,000. The overall 10-year survival was 59%. Distant metastasis occurred in
      21% and local recurrences in 31% of the cases. Survival was significantly better
      in case of radical surgery and small tumours. Long-term survival after treatment
      of OSJ was good if complete surgical excision was achieved. Radiotherapy should
      only be considered to prevent local recurrence if surgery is not complete. The
      possible benefit of current chemotherapy in preventing metastatic disease is
      still questionable. Since other malignant neoplasms associated with OSJ occurred
      in 17% of the cases, lifelong follow up is mandatory for the detection of these
      second primary malignancies.

PMID- 9180230
TI  - Osteogenic sarcoma of the jaws: factors influencing prognosis.
AB  - Thirty cases of osteosarcoma of the jaws were reviewed (20 men and 10 women, mean
      age 34 years). Seventeen lesions occurred in the mandible and 13 in the maxilla.
      Swelling without pain was the most common presenting symptom. Thirteen lesions
      were initially misdiagnosed as odontogenic infections. Numbness as a presenting
      symptom was statistically associated with poor prognosis. Treatment included all
      combinations of surgery, chemotherapy and radiotherapy. Patients receiving
      chemotherapy with four or more agents showed a trend toward better survival with
      71% alive and disease-free at the time of review. Patients' increasing age was
      statistically associated with decreased survival. The average age of survivors
      was 27 years and nonsurvivors, 40 years. Older patients suffered more local
      recurrences which, in all but one case, resulted in mortality. Expectedly, clear
      surgical margins correlated statistically with improved survival. With margins of
      less than 5 mm, 27% of patients were alive and disease-free as compared to 62%
      with surgical margins greater than 5 mm. The importance of early diagnosis,
      definitive surgical treatment and aggressive adjuvant chemotherapy is
      demonstrated. The Proportional Hazards Regression model was employed to evaluate
      the statistical significance of a variety of factors on disease-free and overall
      survival.

PMID- 9180232
TI  - Mesenchymal chondrosarcoma of the maxilla. A case report.
AB  - A case of mesenchymal chondrosarcoma of the maxilla is reported. This rare tumour
      is characterized by slow growth, late metastasis (up to 20 years after first
      presentation) and poor prognosis. The diagnosis is often difficult to make
      because of the low incidence among malignant bone tumours.

PMID- 9180231
TI  - Evaluation of glutathione S-transferase activity in human buccal epithelial
      dysplasias and squamous cell carcinomas.
AB  - Glutathione S-transferase (GST) activity and amount of GST alpha, mu and pi
      isoforms were measured in 40 patients with histopathologically confirmed oral
      epithelial dysplasia (OED) and squamous cell carcinoma of buccal mucosa. The
      results were compared with those of normal mucosa in an equal number of age- and
      sex-matched healthy controls. Mean total GST activities were significantly
      elevated from normal buccal mucosa for mild OED, moderate OED, severe OED and
      squamous cell carcinoma. GST activity of value approximating 100 nmol/min/mg
      distinguished between normal and dysplasia, and of value about 400 nmol/min/mg
      delineated between dysplasia and squamous cell carcinoma were observed. GST pi
      was the predominant class in both the diseased and normal buccal mucosa examined.
      This class pi GST was present at an intracellular concentration, which was
      significantly higher in diseased buccal mucosa than in normal buccal mucosa.
      These results indicated that pi class GST was the major form of this enzyme in
      the cytosolic fraction of oral mucosa. The severity of OED related to squamous
      cell carcinoma development seemed to increase concomitantly with an increase in
      the level of this enzyme. Further studies will validate the role of GST pi
      estimation in predicting the potential malignancy of OED.

PMID- 9180233
TI  - Epithelioid hemangiomas of the maxillofacial area. A report of three cases and a
      review of the literature.
AB  - Epithelioid hemangioma, also named angiolymphoid hyperplasia with eosinophilia,
      is a very rare tumor that arises from vascular structures. The relative incidence
      in the skin of the head and neck area is rather high as compared to other parts
      of the body. Three cases are reported in an atypical location and the
      differential diagnosis with other similar vascular lesions and their pathologic
      features is presented.

PMID- 9180234
TI  - Hemifacial atrophy secondary to poliomyelitis.
AB  - A 25-year-old woman is presented with hemifacial atrophy due to unilateral bulbar
      poliomyelitis infection. Although bulbar poliomyelitis is not an uncommon
      disease, it is rarely a cause of hemifacial asymmetry.

PMID- 9180235
TI  - The short-term effect of autogenous auricular cartilage graft following
      discectomy on the osteoarthrotic temporomandibular joint in sheep.
AB  - The aim of this experimental study was to determine the effect of auricular
      cartilage graft replacement on the progression of experimentally induced
      osteoarthrosis in sheep. Bilateral osteoarthrosis was induced in the sheep
      temporomandibular joint (TMJ). Three months later, discectomy and autogenous
      auricular cartilage grafting were performed unilaterally. At sacrifice, three
      months postrepair and six months postinduction of osteoarthrosis, it was found
      that the untreated side had extensive condylar osteoarthrosis and the grafted
      side showed evidence of fibrous repair. The graft prevented intra-articular
      adhesions and reduced degenerative changes, but there was a tendency towards
      graft perforation. Auricular cartilage grafting was effective in minimizing
      osteoarthrotic effects on the TMJ in the early stages after grafting.

PMID- 9180236
TI  - Photofrin-mediated photodynamic therapy of chemically-induced premalignant
      lesions and squamous cell carcinoma of the palatal mucosa in rats.
AB  - Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an
      animal model of chemically-induced epithelial dysplasia and squamous cell
      carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw
      Photofrin, and using 100 J/cm2 incident light at two activation wavelengths
      (514.5 nm or 625 nm). Two days after PDT, the majority of rats macroscopically
      showed a marked erythema of the entire palatal region. Microscopically all the
      rats showed oedema, haemorrhage, and necrosis of the epithelium of the intermolar
      area. The long-term results were not so favourable. No evidence of disease was
      found in 6 out of 20 rats in the 514.5 nm group and in 2 out of 20 rats in the
      625 nm treated group. Epithelial dysplasia was found in 14 out of 20 rats in the
      514.5 nm group, and in 18 out of 20 rats of the 625 nm treated group. Squamous
      cell carcinomas were found in 4 out of 20 rats treated with 514.5 nm and in 7 out
      of 20 rats in the 625 nm treated groups. Comparing both treatment wavelengths,
      better results were obtained in the 514.5 nm groups as this wavelength gave less
      normal tissue damage. Based on the results of this study the application of PDT
      for the treatment of field cancerization and squamous cell carcinoma of the oral
      cavity, is discussed.

PMID- 9180237
TI  - 47th Annual Meeting of the Study Group on Maxillofacial Surgery and meeting of
      the Working Group on Oral Pathology, within the German Association for Dental,
      Oral and Maxillofacial Medical Science, 16-18 May 1996, Bad Homburg, Germany.

PMID- 9180238
TI  - What targets should lipid-modulating therapy achieve to optimise the prevention
      of coronary heart disease?
AB  - Analysis of trials which have investigated the effects of lowering low density
      lipoprotein (LDL) levels on coronary heart disease (CHD), as determined by
      changes on quantitative coronary angiography and in the incidence of
      cardiovascular events, suggests that the percentage decrease in LDL cholesterol
      provides a better index of outcome than does its absolute level on treatment.
      Additional data suggest that it may be advantageous to employ therapy which not
      only lowers LDL cholesterol but also decreases serum triglyceride and/or
      increases HDL cholesterol. These conclusions have important implications for
      future guidelines on CHD prevention.

PMID- 9180239
TI  - Butter, margarine and serum lipoproteins.
AB  - Intake of trans fatty acids unfavorably affects blood lipoproteins. As margarines
      are a major source of trans, claims for the advantages of margarines over butter
      need to be scrutinized. Here we review dietary trials that directly compared the
      effects of butter and margarine on blood lipids. We identified 20 studies in
      which subjects had stable body weights, and margarine and butter were exchanged
      in the diet at constant energy and fat intake. We calculated the changes in
      average blood lipid levels between study diets (49 comparisons) as a function of
      the percentage of calories as margarine substituted for butter. Replacing 10% of
      calories from butter by hard high-trans stick margarines lowered total serum
      cholesterol by 0.19, LDL by 0.11, and HDL by 0.02 mmol/l, and did not affect the
      total/HDL cholesterol ratio. Soft low-trans tub margarines decreased total
      cholesterol by 0.25 and LDL by 0.20 mmol/l, did not affect HDL, and decreased the
      total/HDL cholesterol ratio by 0.20. Based on the total/HDL cholesterol ratio,
      replacement of 30 g of butter per day by soft tub margarines would theoretically
      predict a reduction in coronary heart disease risk of 10%, while replacement of
      butter by hard, high-trans margarines would have no effect. Replacing butter by
      low-trans soft margarines favorably affects the blood lipoprotein profile and may
      reduce the predicted risk of coronary heart disease, but high-trans hard
      margarines probably confer no benefit over butter.

PMID- 9180240
TI  - A brief review paper of the efficacy and safety of atorvastatin in early clinical
      trials.
AB  - Preclinical and clinical data on atorvastatin, a new 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitor, indicate that it has superior activity
      in treating a variety of dyslipidemic disorders characterized by elevations in
      low-density lipoprotein cholesterol (LDL-C) and/or triglycerides. Results for
      patients randomized in early efficacy and safety studies were combined in one
      database and analyzed. This analysis included a total of 231 atorvastatin-treated
      patients (131 with hypercholesterolemia (HC), 63 with combined hyperlipidemia
      (CH), 36 with hypertriglyceridemia (HTG), and 1 with hyperchylomicronemia
      (Fredrickson Type V)). Patients were treated with a cholesterol-lowering diet
      (National Institutes of Health National Cholesterol Education Program Step 1 diet
      or a more rigorous diet) and either 2.5, 5, 10, 20, 40, or 80 mg/day of
      atorvastatin or placebo. Efficacy was based on percent change from baseline in
      total cholesterol, total triglycerides, LDL-C, very low-density lipoprotein
      cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C),
      apolipoprotein B (apo B), and non-HDL-C/HDL-C. Safety was assessed in all
      randomized patients. Atorvastatin seemed to preferentially lower those lipid and
      lipoprotein component(s) most elevated within each dyslipidemic state: LDL-C in
      patients with HC, triglycerides and VLDL-C in patients with HTG, or all 3 in
      patients with CH. Atorvastatin was well-tolerated with a safety profile similar
      to other drugs in its class.

PMID- 9180241
TI  - Effect of the dietary fat type on arterial thrombosis tendency: systematic
      studies with a rat model.
AB  - To study the influence of dietary fatty acids on arterial thrombosis tendency 65
      groups of male rats were fed diets containing 50% of their digestible energy as
      fat from 32 different oils and fats. After 8 weeks their arterial thrombosis
      tendency was assessed by measuring the obstruction time (OT) of a loop-shaped
      polythene cannula inserted into the abdominal aorta. Using multiple regression
      analysis log10 OT was modelled as a function of the relative amounts of the
      various dietary fatty acids and their combinations. The best fit (R2 = 0.79) was
      obtained for the sums of all monoenoic and (n-6) and (n-3) polyenoic fatty acids,
      which appeared antithrombotic. The fit for the sum of all saturated fatty acids,
      which had a prothrombotic effect, was almost as good (R2 = 0.76). The ratio
      between dietary polyunsaturated and saturated fatty acids (P:S ratio) appeared a
      strong predictor of arterial thrombosis tendency (R2 = 0.77). Marine oils did not
      have a more powerful antithrombotic effect than could be expected on the basis of
      their P:S ratios. Using stepwise regression analysis myristic acid, 14:0, was
      shown to be the strongest prothrombotic fatty acid whereas linoleic acid, 18:2(n
      6), was the strongest antithrombotic fatty acid. Since the number of marine oils
      was very limited the effects of the 'fish fatty acids' eicosapentaenoic acid,
      20:5(n-3) and docosahexaenoic acid, 22:6(n-3), on arterial thrombus formation
      could not be tested reliably. The same appeared true for gamma-linolenic acid,
      18:3(n-6), and stearidonic acid, 18:4(n-3), present in a few vegetable oils only.

PMID- 9180242
TI  - Oxidative tyrosylation of high density lipoprotein impairs biliary sterol
      secretion in rats.
AB  - The oxidation of low density lipoprotein plays a central role in the pathogenesis
      of atherosclerosis. Oxidative modification could also occur in high density
      lipoprotein (HDL), which may alter reverse cholesterol transport. It has recently
      been proposed that myeloperoxidase-generated tyrosyl radical may modify HDL. In
      the present study we have examined whether the oxidative tyrosylation of HDL by
      peroxidase may alter biliary cholesterol secretion and bile acid transformation.
      HDL was modified by exposure to L-tyrosine, H2O2 and peroxidase labelled with
      [14C]cholesterol and injected i.v. into rats with bile diversion. A reduced
      excretion of radioactivity (14-20%) was recovered in the bile of animals
      administered with tyrosylated HDL at the different periods of collection. Both
      labelled cholesterol (14.3%, P < 0.05) and bile acids (18.9%, P < 0.05) were
      decreased in these rats, similarly to results obtained from malondialdehyde
      modified HDL. Consequently, this kind of oxidative modification resulted in a
      loss of the hepatobiliary systems capacity to normally process HDL.

PMID- 9180243
TI  - New indices of ischemic heart disease and aging: studies on the serum levels of
      soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell
      adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic
      heart disease.
AB  - It is known that the expression of intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) on the surface of vascular endothelial
      cells is closely related to the formation of early atherosclerotic lesions. In
      this study, serum soluble ICAM-1(sICAM-1) and soluble VCAM-1(sVCAM-1) were
      determined by sandwich ELISA both in normal healthy individuals (n = 114) and in
      patients with hypercholesterolemia (HC, n = 112) or ischemic heart disease (IHD,
      n = 38) to clarify the significance of the soluble forms of the adhesion
      molecules in the development of atherosclerotic diseases. IHD patients, not HC
      patients, showed significant elevation of sICAM-1, but not of sVCAM-1, compared
      with controls in age and sex-matched subjects. In addition, multiple linear
      regression analysis showed that sICAM-1 was correlated only to the presence of
      IHD but not to age and lipids. Multiple logistic regression analysis revealed
      that sICAM-1 was the most powerful independent predictor of the presence of IHD.
      On the other hand, sVCAM-1, not sICAM-1, was positively correlated to age.
      Multiple linear regression analysis showed that age was the most powerful
      independent predictor of the level of sVCAM-1. These data suggest that sICAM-1
      and sVCAM-1 are useful as indices of clinical manifestations of atherosclerosis
      and aging, respectively.

PMID- 9180244
TI  - Increased serum remnant lipoproteins in patients with apolipoprotein E7 (apo E
      Suita).
AB  - Apolipoprotein (apo) E7 was originally identified by Yamamura et al. in subjects
      with atherosclerotic cardiovascular diseases (J. Clin. Invest. 1984;74:1229).
      However, the lipoprotein abnormalities associated with apo E7 phenotype have not
      been elucidated. In the current study, to clarify the physiological roles of apo
      E7, lipoprotein abnormalities were studied in 12 apo E7 heterozygotes. A total of
      seven subjects were hyperlipidemic and five subjects were normolipidemic. The apo
      E phenotype was apo E7/3 in 11 subjects and apo E7/4 in one subject. Polymerase
      chain reaction revealed that all of the subjects with apo E7 phenotype had the
      same mutation as that of apo E(Suita) as reported previously (J. Biochem.
      1989;105:249). All the hyperlipidemic subjects were over 40 years of age and two
      of them also had and severe coronary heart disease. Ultracentrifugal analysis
      revealed that the cholesterol level both in very low density lipoprotein and in
      intermediate density lipoprotein (IDL) was substantially higher in hyperlipidemic
      apo E7 heterozygotes, compared with control subjects and that the IDL cholesterol
      was also increased even in normolipidemic apo E7 heterozygotes. Polyacrylamide
      gel electrophoresis of lipoproteins showed a midband, which implies the increase
      of remnant lipoproteins, in 11 subjects out of 12, irrespective of the presence
      or absence of hyperlipoproteinemia. In two cases, a broad beta pattern was
      observed similar to that seen in type III hyperlipoproteinemia. Dietary therapy
      was dramatically effective for the treatment of hyperlipidemia in patients with
      apo E7. These findings confirm that apo E is crucial for remnant lipoprotein
      metabolism and that apo E7 is related to the increase in serum remnant
      lipoproteins, which leads to hyperlipoproteinemia in association with obesity,
      aging and impaired glucose metabolism.

PMID- 9180245
TI  - Nuclear factor-kappaB activity and arterial response to balloon injury.
AB  - We studied the effect of arterial balloon injury on nuclear factor-kappaB (NF
      kappaB) mobilization and ICAM-1 expression in untreated rats and rats treated
      with aspirin. Baseline NF-kappaB nuclear binding in smooth muscle cells (SMC)
      increased two-fold within 6 h after balloon injury. The binding returned to
      baseline 3 days after injury. Consistently nuclear staining of p65 active subunit
      increased in the medial SMC following balloon injury. There was no baseline ICAM
      1 expression. Within 3 days after balloon injury there was marked medial ICAM-1
      expression, that localized to neointima 7 days after injury and to regrowing
      endothelial cells 14 days after injury. Treatment with aspirin inhibited NF
      kappaB nuclear translocation and binding and was associated with reduction of
      ICAM-1 expression, SMC proliferation and neointimal thickening following balloon
      injury. These data suggest that transient mobilization of NF-kappaB in vascular
      SMC after balloon injury mediates ICAM-1 expression and is involved in arterial
      response to balloon injury.

PMID- 9180246
TI  - A common W556S mutation in the LDL receptor gene of Danish patients with familial
      hypercholesterolemia encodes a transport-defective protein.
AB  - In a group of unrelated Danish patients with familial hypercholesterolemia (FH)
      we recently reported two common low-density lipoprotein (LDL) receptor mutations,
      W23X and W66G, accounting for 30% of the cases. In this study, we describe
      another common LDL receptor mutation, a G to C transition at cDNA position 1730
      in exon 12, causing a tryptophan to serine substitution in amino acid position
      556 (W556S). In the Danish patients, the W556S mutation was present in 12% of 65
      possible mutant alleles. The pathogenicity of the W556S mutation, which is
      located in one of the five conserved motifs Tyr-Trp-Thr-Asp in the epidermal
      growth factor homology region, was studied in transfected COS-7 cells expressing
      normal and mutant LDL receptor cDNAs. Results obtained by immunofluorescence flow
      cytometry and confocal microscopy, as well as by immunoprecipitation, were
      compatible with complete retention of the mutant protein in the endoplasmic
      reticulum. The transport-defective W556S mutation and the W23X and W66G mutations
      seem to account for about 40% of the LDL receptor defects in Danish families with
      FH.

PMID- 9180247
TI  - Aging of the vascular wall: serum concentration of elastin peptides and elastase
      inhibitors in relation to cardiovascular risk factors. The EVA study.
AB  - The relations of biological markers of extracellular matrix (plasma elastin
      peptides and elastase inhibitors) to the clinical history of cardiovascular
      diseases and risk factors for atherosclerosis were examined in a large population
      study (the EVA Study) on vascular and cognitive aging performed in 1389 men and
      women aged 59-71 years. A moderate decrease in elastin peptides was observed in
      women with a self-reported history of coronary heart disease (P < 0.091) and
      stroke (P < 0.03) as well as with diabetes (P < 0.043). Similar but non
      significant trends were found in men. Furthermore, elastin peptides were
      significantly and positively correlated to HDL-cholesterol and apolipoprotein A1
      in both sexes. On the other hand, elastase inhibitor titers were significantly
      higher in women than in men. A moderate increase was also found in men (P <
      0.097) and women (P < 0.068) with a history of coronary heart disease that
      reached significance level after pooling both sexes (P < 0.014). Furthermore,
      elastase inhibitor titers were significantly and positively related to fibrinogen
      and C reactive protein in either sex. No consistent associations were observed
      between both biological markers of extracellular matrix and age, blood pressure,
      body mass index and tobacco or alcohol consumption. These results suggest that a
      decrease in elastin peptides and an increase in elastase inhibitors might be
      associated with risk factors of atherogenesis as well as with atherosclerosis
      related diseases.

PMID- 9180248
TI  - Leukocyte activation in atherosclerosis: correlation with risk factors.
AB  - Leukocytes have been implicated in the development of atherosclerotic vascular
      diseases, and numerous abnormalities of leukocytes in conjunction with
      atherosclerosis have been reported. The aim of this study of middle-aged
      asymptomatic subjects with early atherosclerosis was to determine whether a
      relationship exists between the levels of plasma markers of leukocyte activation,
      i.e. cytokines and proteases and risk factors for atherosclerosis or the degree
      of atherosclerotic disease. Using ELISAs we measured the plasma levels of
      neutrophil gelatinase-associated lipocalin (NGAL), neutrophil protease 4 (NP4) as
      markers for neutrophil activation, tumor necrosis factor alpha (TNF) and soluble
      TNF receptor-1 (sTNFR-1) as markers of monocyte/macrophage activation in 156
      subjects with asymptomatic carotid artery plaque detected at ultrasound
      examination. Plasma TNF and sTNFR-1 levels were found to correlate with systolic
      blood pressure (r = 0.32, P < 0.04 and r = 0.22, P < 0.05, respectively). plasma
      NGAL level to correlate with diastolic blood pressure (r = 0.22; P < 0.005), the
      plasma levels of sTNFR-1 and NGAL to correlate with age (r = 0.28, P < 0.001 and
      r = 0.20, P < 0.05, respectively). As compared with non-smokers (n = 112),
      smokers (n = 43) had higher plasma levels of TNF (2.9 vs. 1.4 microg/l; P < 0.02)
      and of NP4 (27.5 vs. 23.4 microg/l; P < 0.05). The plasma NGAL level was higher
      in hypertensive women (n = 7) than in normotensive women (n = 85) (109 vs. 87
      microg/l; P < 0.05). We thus demonstrated that, in subjects with asymptomatic
      early atherosclerosis, the plasma levels of markers of systemic leukocyte
      activation were correlated with age and blood pressure, and were higher in
      smokers and hypertensives. These results support the hypothesized relationship
      between the level of systemic leukocyte activation and risk factors for
      atherosclerotic vascular disease.

PMID- 9180249
TI  - Familial lecithin:cholesterol acyltransferase deficiency: molecular analysis of a
      compound heterozygote: LCAT (Arg147 --> Trp) and LCAT (Tyr171 --> Stop).
AB  - Lecithin:cholesterol acyltransferase (LCAT) is responsible for the formation of
      the majority of plasma cholesteryl esters. Familial LCAT deficiency is associated
      with corneal opacity, anemia and proteinurea and typically results in renal
      failure in the 4-5th decade; this syndrome is equally characterized by the quasi
      absence of plasma LCAT activity with variable enzyme mass and very low levels of
      plasma cholesteryl esters. In this study, we report detailed analyses of plasma
      lipids and lipoprotein profile in two sisters (CM and ML) presenting classical
      homozygous LCAT-deficiency; the younger sibling (CM) had proteinurea from an
      early age whereas the older sister (ML) has never exhibited renal dysfunction. We
      investigated the molecular defect in the 45 year-old woman (proband CM)
      exhibiting all clinical and biochemical features of familial LCAT deficiency: a
      plasma cholesterol level of 105 mg/dl, of which 95% was unesterified, an HDL
      cholesterol of 6.5 mg/dl and an apo A-I level of 52 mg/dl. The proband (CM)
      displayed a plasma cholesterol esterification rate which corresponded to 2% of
      normal LCAT activity; plasma LCAT protein concentration was 0.56 microg/ml and
      equivalent to approximately 10% of normal LCAT mass. Analysis by single strand
      conformation polymorphism (SSCP) of the PCR products corresponding to exons 4 and
      5 of the LCAT gene revealed a visible band shift. Sequence analyses of exons 4 +
      5 revealed two separate single point mutations: a C --> T transition replacing
      Arg147 by Trp and a T --> G transition converting Tyr171 to a stop codon. The
      presence of these two point mutations was confirmed by restriction enzyme
      analyses: the C --> T transition abolished a MwoI site whereas the T --> G
      transition created an AvrII site. The Arg147 mutation was associated with a non
      secreted protein. The Tyr171 mutation resulted in formation of a truncated
      protein lacking the catalytic site. In summary, we have identified an LCAT
      deficient patient corresponding to a compound heterozygote for the Arg147 --> Trp
      mutation and a new molecular defect involving a Tyr171 --> Stop mutation in the
      LCAT gene.

PMID- 9180250
TI  - Arachidonic acid of platelet phospholipids is decreased after extracorporeal
      removal of plasma low density lipoproteins in patients with familial
      hypercholesterolemia.
AB  - Platelet phospholipid composition was analyzed before and after extracorporeal
      removal of low density lipoproteins (LDL) by LDL apheresis in six patients with
      familial hypercholesterolemia. Elevated levels of total plasma cholesterol and
      the portion of plasma cholesterol carried by LDL were reduced by 56 and 66% after
      LDL apheresis. Platelet cholesterol contents remained unaffected. While the
      phosphatidylcholine (PC):sphingomyelin (SM) ratio in plasma lipoproteins was
      increased by 22% following apheresis, the same parameter was lowered by 14% in
      platelets. LDL apheresis induced decreases in the percentages of distinct
      molecular species containing arachidonic acid in platelet diacyl subgroups of PC,
      phosphatidylinositol (PI) and phosphatidylserine (PS) as well as in alkenylacyl
      (plasmalogen) phosphatidylethanolamine (PE). Directly after apheresis, the
      percentages of molecular species with arachidonic acid of diacyl PC, diacyl PI
      and alkenylacyl PE were reduced by 20, 23 and 8%, respectively. Two days after
      the procedure, total arachidonic acid of diacyl PC, diacyl PS and alkenylacyl PE
      was lowered by 11, 20 and 8%. Overall, the amount of phospholipid bound
      arachidonic acid was reduced by 16% after apheresis (from 79.1 to 66.4 nmol/10(8)
      platelets). The results are thus in agreement with previous data indicating
      decreased phospholipid bound arachidonic acid in red blood cells after apheresis
      (Engelman B. Brautigam C, Kulschar R et al. Biochim Biophys Acta 1994:1196:154).
      Urinary 2,3-dinor thromboxane B2, an estimate of platelet thromboxane A2 (TXA2)
      production, tended to be decreased following the procedure. The percentage change
      in the TXA2 metabolite was positively related to the magnitude of change induced
      by apheresis in phospholipid bound arachidonic acid. In summary, the results
      suggest that in patients with hypercholesterolemia, the level of plasma LDL is an
      important determinant of the arachidonic acid content of several platelet
      phospholipids.

PMID- 9180251
TI  - Serum bilirubin distribution and its relation to cardiovascular risk in children
      and young adults.
AB  - There is evidence that bilirubin functions as an endogenous tissue protector by
      its antioxidant and anti-complement actions, properties that are relevant to
      atherogenesis. Serum bilirubin distribution and its relation to cardiovascular
      risk were examined in 4156 individuals aged 5-30 years from a biracial (black
      white) community. Bilirubin levels showed significant differences related to race
      (whites > blacks) and sex (males > females, except in 5-10 year olds). In males
      the levels increased with age up to 24 years, while in females the changes were
      less conspicuous. Both adiposity and cigarette smoking associated independently
      and inversely with bilirubin. In addition, serum bilirubin correlated positively
      with HDL cholesterol and inversely with triglycerides, VLDL cholesterol, LDL
      cholesterol, insulin, glucose and systolic blood pressure although these
      correlations were significant only in certain age-race-sex groups. Offspring with
      a parental history of heart attack or hypertension had consistently lower
      bilirubin levels than those without such parental history. Thus, bilirubin may be
      an inverse risk factor for cardiovascular disease.

PMID- 9180252
TI  - Associations of ankle-brachial index with clinical coronary heart disease, stroke
      and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk
      in Communities (ARIC) Study.
AB  - The resting ankle-brachial index (ABI) is a non-invasive method to assess the
      patency of the lower extremity arterial system and to screen for the presence of
      peripheral occlusive arterial disease. To determine how the ABI is associated
      with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque
      and far wall intimal-medial thickness (IMT) of the carotid and popliteal
      arteries, we conducted analyses in 15 106 middle-aged adults from the baseline
      examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study.
      The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and
      preclinical carotid plaque increased with decreasing ABI levels, particularly at
      those of < 0.90. Individuals with ABI < 0.90 were twice as likely to have
      prevalent CHD as those with ABI > 0.90 (age-adjusted odds ratio (OR) ranging from
      2.2 (95% CI: 1.0-5.1) in African-American men to 3.3 (95% CI: 2.1-5.0) in white
      men). Men with ABI < 0.90 were more than four times as likely to have stroke/TIA
      as those with ABI > 0.90 (age-adjusted OR: 4.2 (95% CI: 1.8-9.5) in African
      American men and 4.9 (95% CI: 2.6-9.0) in white men). In women the association
      was weaker and not statistically significant. Among those free of clinical
      cardiovascular disease, individuals with ABI < or = 0.90 had statistically
      significantly higher prevalence of preclinical carotid plaque compared to those
      with ABI > 0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0-1.9) in white
      women to 2.6 (95% CI: 1.0-6.6) in african-american men). The ABI was also
      inversely associated with far wall IMT of the carotid arteries (in both men and
      women) and the popliteal arteries (in men only). The associations of ABI with
      clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and
      popliteal arteries were attenuated and often not statistically significant after
      further adjustment for LDL cholesterol, cigarette smoking, hypertension and
      diabetes. These data demonstrate that low ABI levels, particularly those of <
      0.90, are indicative of generalized atherosclerosis.

PMID- 9180253
TI  - Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in
      beta-thalassemia.
AB  - Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile.
      In asymptomatic heterozygotes the lipid pattern is less markedly affected but
      interestingly related to a diminished cardiovascular risk. The extent and
      significance of these findings are still a matter of debate and no data are
      available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta
      thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age
      matched controls were investigated and their plasma lipoprotein profile and
      apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12
      TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta
      thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P
      disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL
      cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration
      than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, 
      46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were
      triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein
      depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B
      plasma levels but only minor lipoprotein abnormalities with respect to the
      controls. BMT-P lipoprotein composition was intermediate between HT-P and normal
      subjects. Apo(a) plasma levels did not differ among the groups. A higher
      prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same
      'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT
      C or controls. Since liver cirrhosis is almost always present in HT-P, it is
      conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to
      diminished apolipoprotein glycation may be involved. In TT-C a partially improved
      cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and
      apo B), thus justifying the claim for a low prevalence of ischemic heart disease,
      but no Lp(a) plasma level modification could be detected.

PMID- 9180254
TI  - Serum antioxidant status in hypobetalipoproteinaemia.

PMID- 9180255
TI  - MTHFR thermolabile genotype frequencies and longevity in Northern Ireland.

PMID- 9180256
TI  - The E. coli SRP: preferences of a targeting factor.
AB  - Research on the targeting of proteins to the cytoplasmic membrane of E. coli has
      mainly focused on the so-called 'general secretory pathway' (GSP) which involves
      the Sec-proteins. Recently, evidence has been obtained for an alternative
      targeting pathway in E. coli which involves the signal recognition particle
      (SRP). The constituents of this SRP pathway in E. coli are homologous to those of
      the well-characterized eukaryotic SRP pathway, which is the main targeting
      pathway for both proteins translocated across and inserted into the endoplasmic
      reticulum membrane. However, until recently, no clear function could be assigned
      to the SRP in E. coli. New studies point to an important role of the E. coli SRP
      in the assembly of inner membrane proteins.

PMID- 9180257
TI  - Cloning and recombinant expression of rat and human kynureninase.
AB  - Kynureninase [E.C.3.7.1.3.] is one of the enzymes involved in the biosynthesis of
      NAD cofactors from tryptophan through the kynurenine pathway. By tryptic and CNBr
      digestion of purified rat liver kynureninase, we obtained about 28% of the amino
      acid sequence of the enzyme. The rat kynureninase cDNA, isolated by means of
      reverse-transcribed polymerase chain reaction and hybridization screening, codes
      for a polypeptide of 464 amino acids. Northern blot analysis revealed the
      synthesis of a 2.0 kb rat kynureninase mRNA. A cDNA encoding human liver
      kynureninase was also isolated. The deduced amino acid sequence is 85% identical
      to that of the rat protein. COS-1 cells were transfected with both cDNAs. The Km
      values of the rat enzyme, for L-kynurenine and DL-3-hydroxykynurenine, were 440
      +/- 20 microM and 32 +/- 5 microM and of the human enzyme 440 /- 20 microM and 49
      +/- 6 microM, respectively. Interestingly, COS-1 cells transfected with the cDNA
      coding for rat kynureninase also display cysteine-conjugate beta-lyase activity.

PMID- 9180258
TI  - Subunit interactions in the Escherichia coli protein translocase: SecE and SecG
      associate independently with SecY.
AB  - We used hexahistidine-tagged SecE and SecY to study how the core subunits (SecY,
      SecE and SecG) of Escherichia coli protein translocase interact with each other.
      Detergent extracts were prepared from the plasma membranes and fractionated by
      Ni2+-NTA agarose affinity binding. Although His6-SecE, expressed in wild-type
      cells, brought down both SecY and SecG, neither of them was brought down when the
      same protein was expressed in the secY24 mutant cells. His6-SecY brought down
      both SecE and SecG, as expected. Interestingly, His6-SecY24 was able to bring
      down SecG but not SecE. These results confirm our previous conclusion that the
      secY24 alteration impairs the SecY-SecE interaction, and demonstrate that SecY
      and SecG can form a complex that does not contain SecE. Likewise, SecY-SecE
      complex could be isolated from the secG-deleted strain. The trimeric complex, in
      detergent extracts, dissociated at a critical temperature between 23 and 26
      degrees C, whereas the SecY-SecE complex without SecG dissociated at a slightly
      lower temperature (20-23 degrees C). We conclude that each of SecE and SecG
      independently binds to SecY, the central subunit of protein translocase, although
      the trimeric complex is more stable than the binary complexes.

PMID- 9180259
TI  - Induction of glutathione synthetase by 1,10-phenanthroline.
AB  - The differential display (DD) was employed to identify the gene(s) responsible
      for 1,10-phenanthroline (OP)-induced apoptosis in murine tumor cells (Sun, Y.,
      Bian, J., Wang, Y. and Jacobs, C. (1997) Oncogene 14, 385-393 [1]). An OP
      inducible gene was isolated which encodes mouse glutathione synthetase (GSS). The
      GSS mRNA level began to increase 6 h post OP treatment and remained at a high
      level thereafter up to 24 h tested. Induction of GSS was found not to be
      associated with p53 activation. No significant induction of DNA fragmentation was
      detected in two murine tumor lines upon GSS transfection. This is the first
      observation indicating that GSS is inducible rather specifically by a metal
      chelator and that induction of GSS, however, is not sufficient to induce
      apoptosis. It may merely reflect a cellular response to OP-induced redox
      disturbance.

PMID- 9180260
TI  - Deletion in the Z-line region of the titin gene in a baby hamster kidney cell
      line, BHK-21-Bi.
AB  - The gene for titin, a 4MDa myofibrillar protein, was analysed in golden hamster
      DNAs from different sources, using human cDNA probes and PCR. In the DNA from the
      BHK-21-Bi subline of baby hamster kidney cells, extended sequences coding for Z
      line associated domains were missing, indicating a deletion that renders titin
      non-functional. These sequences were present in the original BHK-21 line and in
      hamster DNAs. Our finding shows that, due to the absence of selective pressure on
      a gene's function, genomic deterioration can occur in a permanent cell line and
      can lead to a loss of overlapping DNA stretches in both autosomes.

PMID- 9180262
TI  - Stimulation of spinach (Spinacia oleracea) chloroplast fructose-1,6
      bisphosphatase by mercuric ions.
AB  - Chloroplast fructose-1,6-bisphosphatase can exist in an active reduced form or a
      less active oxidised form. Oxidised fructose bisphosphatase from spinach
      (Spinacia oleracea) could be stimulated up to many hundred-fold by 0.1 mM HgCl2
      whereas fructose bisphosphatases from rabbit, yeast, a non-chloroplast enzyme
      from spinach and the reduced chloroplast enzyme were only inhibited by HgCl2.
      Stimulation of the enzyme was maximal at pH 8.0 and low magnesium concentrations
      where the oxidised enzyme normally has little activity.

PMID- 9180261
TI  - DNA binding sites recognised in vitro by a knotted class 1 homeodomain protein
      encoded by the hooded gene, k, in barley (Hordeum vulgare).
AB  - The homeodomain of the knotted classes of transcription factors from plants
      differs from the well characterized Antp/En type homeodomains from Drosophila at
      key amino acid residues contributing to the DNA binding. A cDNA, Hvh21, derived
      from the hooded gene and encoding a full length homolog of knotted1 from maize
      was isolated from barley seedlings and expressed as a maltose binding protein
      fusion in E. coli. The purified HvH21-fusion protein selected DNA fragments with
      1-3 copies of the sequence TGAC. Gel shift experiments showed that the TGAC
      element was required for binding and the results further indicate that the HvH21
      fusion protein binds DNA as a monomer.

PMID- 9180263
TI  - Activation of Stat1 and subsequent transcription of inducible nitric oxide
      synthase gene in C6 glioma cells is independent of interferon-gamma-induced MAPK
      activation that is mediated by p21ras.
AB  - Rat C6 glioma cells have been used to characterize molecular events involved in
      the regulation of inducible nitric oxide synthase (iNOS) gene expression
      stimulated by interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). IFNs
      induce a signaling event which involves activation of Stat1 transcription factor.
      Previous studies have shown that IFNs also induce extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK) activation. However, the
      mechanisms by which IFNs stimulate MAPK activation remain elusive. Here we show
      that in C6 glioma cells, transiently expressing the dominant-negative form of c
      Ha-Ras (Asn-17) abrogated IFN-gamma-induced ERK1 and ERK2 activation.
      Furthermore, PD98059, a specific MEK1 inhibitor, also blocked this activation.
      These results indicate that p21ras and MEK1 are required for IFN-gamma-induced
      ERK1 and ERK2 activation. Recent studies have reported that MAPK is responsible
      for serine phosphorylation of Stat1 which is required for Stat1's DNA binding and
      maximal transcriptional activity. Thus, we examined the role of the Ras-MAPK
      pathway in Stat1 activation and subsequent iNOS induction in C6 glioma cells.
      Further experiments showed that neither Asn-17 Ras expression nor concentrations
      of PD98059, which completely abrogated IFN-gamma-induced ERK1 and ERK2
      activation, affected Stat1 DNA binding activity or iNOS induction, indicating
      that the Ras-MAPK pathway does not appear to be involved in the activation of
      Stat1 and subsequent iNOS induction in C6 glioma cells.

PMID- 9180266
TI  - Transcriptional activity and constitutive nuclear localization of the ETS protein
      Elf-1.
AB  - Elf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein
      family. It can bind to DNA target sequences within a variety of cytokine genes.
      We demonstrate that Elf-1 is constitutively localized in the nucleus which is
      dependent on the presence of amino acids 86-265. Analysis of Gal4-Elf-1 fusion
      proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a
      transcriptional activation domain, the activity of which is attenuated by an
      internal repression domain. Furthermore, Elf-1 interacts specifically with the
      E74 target sequence and can stimulate transcription driven by the E74 site
      independent of mitogenic signaling. Thus, Elf-1 is able to stimulate gene
      transcription which may be required for the development and activity of
      lymphocytes.

PMID- 9180264
TI  - Uncoupling protein-3: a new member of the mitochondrial carrier family with
      tissue-specific expression.
AB  - Brown adipose tissue (BAT) and skeletal muscle are important sites of
      nonshivering thermogenesis. The uncoupling protein-1 (UCP1) is the main effector
      of nonshivering thermogenesis in BAT and the recently described ubiquitous UCP2
      [1] has been implicated in energy balance. In an attempt to better understand the
      biochemical events underlying nonshivering thermogenesis in muscle, we screened a
      human skeletal muscle cDNA library and isolated three clones: UCP2, UCP3L and
      UCP3S. The novel UCP3 was 57% and 73% identical to human UCP1 and UCP2,
      respectively, highly skeletal muscle-specific and its expression was unaffected
      by cold acclimation. This new member of the UCP family is a candidate protein for
      the modulation of the respiratory control in skeletal muscle.

PMID- 9180265
TI  - Stimulation of human keratinocyte growth by alginate oligosaccharides, a possible
      co-factor for epidermal growth factor in cell culture.
AB  - Oligosaccharides, involved in regulation of plant developmental and defensive
      processes, were tested to determine their ability to enhance proliferation of
      human keratinocytes. A mixture of alginate oligosaccharides remarkably stimulated
      keratinocyte growth and [3H]thymidine uptake in the presence of epidermal growth
      factor (EGF). The activity was comparable to bovine pituitary extract, a common
      complement in keratinocyte culture, and additive on BPE-induced stimulation. The
      most effective oligosaccharide in the mixture was identified and its chemical
      structure was determined. These findings demonstrate a novel activity of alginate
      oligosaccharide(s) in keratinocyte growth and suggest a possible co-factor for
      EGF-dependent stimulation in medium for keratinocytes.

PMID- 9180267
TI  - Molecular heterogeneity of the cDNA encoding a 74-kDa regulatory subunit (B" or
      delta) of human protein phosphatase 2A.
AB  - Two cDNAs for possible splicing variants of a 74-kDa regulatory subunit (B" or
      delta) of human protein phosphatase 2A, were isolated. These variants were
      identified from human cerebral cortex by library screening and PCR, and
      designated delta1 and delta3 isoforms, while the previously reported isoform
      [Tanabe et al. (1996) FEBS Lett. 379, 107-1111 was designated delta2. Compared
      with the delta2 isoform, the delta1 isoform contained a 32-residue insertion
      beginning at residue 84, and consisted of 602 amino acids in all. The delta3
      isoform lacked a 74-residue sequence corresponding to residues 1083 of the delta2
      isoform, and consisted of 496 amino acids. Using isoform-specific antipeptide
      antisera, the 74-kDa subunit (B" or delta) originally purified from human
      erythrocytes was identified as the delta1 isoform.

PMID- 9180268
TI  - Reversible inhibition of sheep liver sorbitol dehydrogenase by the
      antidiabetogenic drug 2-hydroxymethyl-4-(4-N,N-dimethylaminosulfonyl-1
      piperazino) pyrimidine.
AB  - The mechanism of the inhibition of sheep liver sorbitol dehydrogenase by the
      novel antidiabetogenic drug 2-hydroxymethyl-4-(4-N,N-dimethylaminosulfonyl-1
      piperazino) pyrimidine has been investigated by steady-state kinetics over the
      range pH 5-10. The pyrimidine derivative exhibits mixed inhibition with respect
      to sorbitol, fructose and coenzyme, due to the formation of enzyme-inhibitor and
      enzyme-NAD(H)-inhibitor complexes. The formation of each of the binary and
      ternary complexes is inhibited by protonation and deprotonation of groups which,
      in the enzyme-inhibitor complex, have pK values of 6.6 and 8.0, respectively.

PMID- 9180270
TI  - Time-resolved fluorescence studies on site-directed mutants of human serum
      albumin.
AB  - Human serum albumin (HSA) contains a single tryptophan residue at position 214.
      The emission properties of tryptophan 214 from recombinant albumins, namely,
      normal HSA, FDH-HSA and a methionine 218 HSA were examined. In all cases, the
      excited state lifetimes were best described by a two component model consisting
      mainly of a Lorentzian distribution. The centers of these distributions were 5.60
      ns for HSA, 4.23 ns for FDH-HSA, and 6.08 ns for Met-218 HSA. The global
      rotational correlation times of the three HSAs were near 41 ns while the
      amplitude and rate of the local motion varied. These changes in the lifetimes and
      mobilities suggest perturbation in the local protein environment near tryptophan
      214 as a consequence of the amino acid substitutions.

PMID- 9180269
TI  - Cloning, expression and characterisation of murine procathepsin E.
AB  - The cDNA encoding murine procathepsin E was isolated and sequenced and
      recombinant enzyme was produced in Escherichia coli. The activity of the purified
      recombinant mouse cathepsin E was characterised quantitatively using two
      synthetic peptide substrates and naturally occurring inhibitors. The majority of
      the recombinant enzyme was present as a homodimer (Mr approximately 80) in which
      the two monomers were linked by an intermolecular disulfide bond. By analogy to
      previous studies with human cathepsin E, this is most likely a consequence of the
      presence of a unique cysteine residue near the N-terminus of the mature
      proteinase. The availability of (i) recombinant murine enzyme in reasonable
      quantities and (ii) a full-length cDNA now enables structural investigations and
      attempts to generate 'knock-out' mice deficient in this important aspartic
      proteinase to be undertaken.

PMID- 9180271
TI  - Different actin affinities of human cardiac essential myosin light chain
      isoforms.
AB  - The N terminus of myosin light chain 1 (MLC-1) of skeletal muscle bind to the C
      terminus of actin. We investigated whether the N termini of human cardiac MLC-1
      isoforms likewise bind to actin. Furthermore, we investigated whether the N
      terminal sequence 5-15 (P5-14) of MLC-1 of human atrium (ALC-1) and ventricle
      (VLC-1) bind with different affinities to actin. Affinity beads were produced by
      covalently coupling a synthetic peptide corresponding to the N-terminal sequence
      4-14 of human VLC-1 to aminohexylagarose in order to bind G-actin. We found, that
      G-actin specifically binds to the affinity beads. Furthermore, preincubation of G
      actin with P5-14 of both ALC-1 and VLC-1 decreased the amount of G-actin
      recovered from the affinity beads in a concentration-dependent manner. The half
      maximal effective concentrations, however were significantly (p < 0.01) different
      being 0.32 +/- 0.02 microM and 0.71 +/- 0.02 microM for the VLC-1 and ALC-1
      peptide, respectively. The appropriate scrambled peptides were without effect up
      to 3 microM. These results demonstrate the specific interaction between the N
      terminal domains of human cardiac MLC-1 isoforms and actin and reveal different
      actin affinities of MLC-1 isoforms. Weak binding of ALC-1 to actin could explain
      the higher cycling kinetics of cross-bridges with ALC-1 compared to those with
      VLC-1.

PMID- 9180272
TI  - Essential role of the beta subunit in modulation of C-class L-type Ca2+ channels
      by intracellular pH.
AB  - Elevation of intracellular pH (pHi) enhances the activity of native L-type Ca2+
      channels in cardiac and smooth muscle. We studied the modulation by pHi of
      expressed L-type Ca2+ channels comprised of either the alpha1c subunits alone or
      of alpha1c plus beta2a subunits. Ca2+ channels were expressed in human embryonic
      kidney cells (HEK 293) and pHi was increased from a basal level of 7.3 to 8.3 by
      exposure of cells to NH4Cl (20 mM) or by elevation of extracellular pH to 8.5.
      Elevation of pHi enhanced the activity of Ca2+ channels derived by coexpression
      of alpah1c and beta2a subunits. This alkalosis-induced stimulation of channel
      activity was mainly due to an increase in channel availability. Channels derived
      by expression of alpha1c alone were not affected by intracellular alkalosis. Our
      results demonstrate that the pHi sensitivity of L-type Ca2+ channels is conferred
      by the beta subunit of the channel complex.

PMID- 9180273
TI  - The heterodimer of the Ca2+-binding proteins MRP8 and MRP14 binds to arachidonic
      acid.
AB  - The S100 proteins MRP8 and MRP14 have been shown to be expressed by myeloid cells
      during inflammatory reactions. Since the majority of S100 proteins exhibit their
      biological activity when associated as complex it was investigated whether murine
      MRP8 and MRP14 form heterodimers and whether this complex may bind lipids of the
      cell membrane. This is of particular importance since their anchoring into the
      plasma membrane is unclear although upon calcium binding the proteins translocate
      from the cytoplasma to the cytoskeleton and the plasma membrane. Using
      recombinant proteins we could show that not the monomers but only the
      heterodimers specifically bind arachidonic acid. This finding opens new
      perspectives for the role of MRP8 and MRP14 in acute and chronic inflammatory
      processes.

PMID- 9180274
TI  - pH dependence of bovine mast cell tryptase catalytic activity and of its
      inhibition by 4',6-diamidino-2-phenylindole.
AB  - Tryptases are oligomeric enzymes localized in the secretory granules of mast
      cells. Their role(s) in vivo has yet to be clarified and the lack of powerful and
      specific inhibitors has hampered the comprehension of the biological functions of
      these enzymes. In this paper, we identify 4',6-diamidino-2-phenylindole as a
      potent inhibitor for bovine tryptase. This inhibitory effect and the enzyme
      catalyzed hydrolysis of the synthetic substrate Boc-Phe-Ser-Arg-methyl-coumarin
      were investigated in the pH range of 6.0-9.0. On the basis of the pK shifts
      occurring upon formation of the inhibitor(substrate)/enzyme complexes, some
      aminoacidic groups are proposed to play a role in such interactions.

PMID- 9180275
TI  - Biogenesis of Candida albicans Can1 permease expressed in Saccharomyces
      cerevisiae.
AB  - The Candida albicans CAN1 gene, encoding a high-affinity permease for arginine,
      lysine and histidine, was tagged at its C-terminus with a c-myc epitope and
      introduced into strains of Saccharomyces cerevisiae lacking basic amino acid
      permeases. The expression levels of Ca-Can1p were influenced by the available
      nitrogen source, being almost negligible when cells were grown in the presence of
      ammonia. Ca-Can1p was shown to follow the secretory pathway in S. cerevisiae. Ca
      Can1p activity was not detected in a secretion-defective sec1-1 mutant grown at a
      non-permissive temperature. Shr3p, an ER protein that participates in the
      biogenesis of amino acid permeases was also required for the functional
      expression of Ca-Can1p. The shr3 mutation does not affect the affinity for
      substrate but does decrease the number of Can1p molecules reaching the plasma
      membrane.

PMID- 9180276
TI  - Different utrophin and dystrophin properties related to their vascular smooth
      muscle distributions.
AB  - Monoclonal antibodies used to distinguish between dystrophin and utrophin were
      systematically applied to skeletal muscles containing arteries and veins. Small
      arteries were found to contain long forms of both utrophin and dystrophin, while
      small veins contained only long forms of utrophin. In addition, all sizes of
      vascular smooth muscles were demonstrated to contain another related Mr 80 kDa
      protein (possibly a short utrophin transcript). Regardless of their tissue
      distributions, we assumed that each of these molecules had distinct properties,
      i.e. dystrophin with a mechanical function and utrophin with an architectural
      function. This difference in the roles of dystrophin and utrophin could reduce
      the efficiency of protection against muscle membrane degeneration when utrophin
      overexpression is programmed.

PMID- 9180277
TI  - Regulation of the DNA binding of p53 by its interaction with protein kinase CK2.
AB  - Some of the numerous functions of the growth suppressor protein p53 are regulated
      by its interaction with viral and cellular proteins. C-terminal sequences of p53
      are implicated in binding to the regulatory beta-subunit of protein kinase CK2.
      Using a p53-specific DNA binding element we found that the beta-subunit of CK2
      inhibited the DNA binding of p53 whereas the alpha-subunit had no influence. The
      CK2 holoenzyme consisting of two alpha- and two beta-subunits led to a supershift
      in DNA binding of p53 similar to the p53-specific monoclonal antibody PAb421 as
      well as the C-terminus of p53. Thus, our results showed an individual role of the
      free beta-subunit of CK2 on the DNA binding activity of p53.

PMID- 9180278
TI  - Alzheimer's soluble amyloid beta is a normal component of human urine.
AB  - Soluble A beta (Sa beta) is normally present at a low concentration in human
      plasma and cerebrospinal fluid. Although the factors involved in the regulation
      of Sa beta plasma levels are still unknown, we have explored its excretion in the
      urine as one of the possible homeostatic mechanisms. The presence of Sa beta in
      the urine was investigated via immunoprecipitation experiments with anti-A beta
      antibodies followed by detection and identification by immunoblot, MALDI mass
      spectrometry and sequence analysis. Soluble A beta (4.3 kDa) immunoreactivity was
      present in the urine of normal donors, Down's syndrome individuals as well as in
      patients with renal disorders exhibiting glomerular or mixed proteinuria. Edman
      degradation of the immunoprecipitated material yielded the intact A beta N
      terminus and mass spectra analysis indicated the existence of a major component
      at mlz 4327, corresponding to the molecular mass of A beta1-40. Semiquantitative
      data obtained from the immunoprecipitation experiments indicate that under normal
      conditions the daily excretion of intact Sa beta in the urine represents less
      than 1% of the circulating pool.

PMID- 9180279
TI  - Serine-threonine protein kinase activity of Elm1p, a regulator of morphologic
      differentiation in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae gene ELM1 regulates morphologic differentiation and
      its nucleotide sequence predicts a novel protein kinase. Elm1p was expressed in
      yeast and insect cells and purified. Elm1p displayed protein kinase activity in
      autophosphorylation assays and towards exogenous substrates. Serine and threonine
      residues were identified as the acceptors in these reactions. These data together
      with previous genetic analysis of ELM1 function indicate that phosphorylation on
      serine and/or threonine residues of a particular substrate or set of substrates
      by Elm1p is required for repression of the filamentous growth differentiation
      state.

PMID- 9180280
TI  - Role of inward K+ channel located at carrot plasma membrane in signal cross
      talking of cAMP with Ca2+ cascade.
AB  - Treatment of cultured carrot cells with dibutyryl cAMP or forskolin resulted in
      the appreciable decrease in extracellular K+ concentration. This decrease was
      found to be transient and the concentration of the ion in the culture medium
      restored to the original level within few minutes. The cAMP-induced decrease in
      K+ level in the medium was almost completely inhibited when carrot cells were
      incubated in the presence of K+ channel blockers, CsCl and tetraethylammonium
      chloride. Appreciable amounts of 45Ca2+ were discharged from 45Ca2+-loaded inside
      out vesicles of carrot plasma membrane by the stimulation with cAMP, however, the
      release of the ion was significantly inhibited in the presence of the K+ channel
      blockers. The release of 45Ca2+ from the vesicles was also observed when K+
      current was evoked with an ionophore, valinomycin, even in the absence of cAMP.
      These results suggest that the gating of some of the inward K+ channels located
      at plasma membrane of cultured carrot cells is controlled by cytoplasmic
      concentration of cAMP and the inward K+ current across the plasma membrane
      induced by the nucleotide elicits Ca2+ influx into the cells possibly by the
      activation of voltage-dependent Ca2+ channels.

PMID- 9180281
TI  - Fre2, a proviral integration site of Friend murine leukemia virus that is closely
      linked to Fv2.
AB  - Friend murine leukemia virus (F-MuLV) induces leukemia by integration into the
      cellular genome, thereby changing the structure or expression of cellular
      oncogenes. In this report we describe a new F-MuLV integration site Fre2 isolated
      from splenic DNA of an erythroleukemic animal. This site was found to be
      rearranged in six out of 64 tumors tested; however, in five out of these six
      cases no F-MuLV proviruses could be detected in the vicinity of the rearrangement
      sites. The rearrangements represented closely clustered chromosomal breakpoints,
      presumably chromosomal translocations. Exons transcribed into differentially
      spliced mRNAs of 1.9 and 3.7 kb have been found near the breakpoint. Fre2 is
      closely linked to Fv2, a locus on mouse chromosome 9 involved in erythropoiesis.
      Sequences homologous to Fre2 could not be found in the gene databases.

PMID- 9180283
TI  - Long-lasting complete remission in patients with hairy cell leukemia treated with
      2-CdA: a 5-year survey.
AB  - Between January 1991 and January 1994, 40 patients with hairy-cell leukemia
      (HCL), 30 males and 10 females, with a median age of 54 years, were treated with
      a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day
      continuous infusion for 7 days. Thirteen patients were untreated and 27 had
      previously received alpha-interferon. Thirty out of 40 patients (75%) achieved
      complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up
      duration for patients in CR has been 48 months (range 30-66). Five of the
      complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after
      treatment as documented by the increase of hairy cells (Hc) in the bone marrow
      and two of them, who were retreated with 2-CdA after showing an initial
      impairment of peripheral blood values, obtained a second CR. The remaining three
      relapsed patients were never retreated and still show normal peripheral counts
      after 30, 38 and 40 months. Twelve of the continuous complete responder patients
      are still in CR after more than 5 years. In contrast, 8 out of 10 partial
      responders progressed after 8-36 months and all of them were retreated with 2-CdA
      at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR,
      three a better PR and one patient died 6 months after the second 2-CdA course
      because of infectious complications. Two additional patients, both in CR, died
      after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted
      of febrile episodes recorded in 16 patients: in seven of them, fever lasted only
      24-48 h after the end of treatment and was apparently not infection-related. In
      the remaining nine patients, showing in addition severe neutropenia (neutrophils
      less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring
      systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2
      CdA induces a very high proportion of complete and long-lasting remissions in
      patients with HCL. In a number of cases relapse at bone marrow level may not
      affect peripheral blood values for prolonged time. However, in those patients
      with initial pancytopenia a retreatment with 2-CdA is still effective in inducing
      a durable second CR.

PMID- 9180282
TI  - Effects of homoharringtonine alone and in combination with alpha interferon and
      cytosine arabinoside on 'in vitro' growth and induction of apoptosis in chronic
      myeloid leukemia and normal hematopoietic progenitors.
AB  - Homoharringtonine (HHT) is a cephalotaxine alkaloid that showed clinical efficacy
      in the chronic phase of chronic myeloid leukemia (Ph1+CML). As a single agent, it
      resulted in effectively controlling leukocytosis and in producing sporadic
      karyotypic conversions; its clinical use in combination with interferon (IFN
      alpha) for the treatment of CML could thus be considered. In this study we
      evaluated the growth inhibition and the induction of apoptosis determined by HHT
      alone and in combination with IFN-alpha and cytosine arabinoside (Ara-C) on
      normal and CML (both in chronic, CML-CP and in blastic phase; CML-BP)
      hematopoietic progenitors. HHT is able to determine a dose-dependent cell growth
      inhibition; evaluation of cytotoxic activity on semisolid cultures showed an
      activity significantly higher on CML-CP than on normal cells (P = 0.02 for HHT 50
      ng/ml and P = 0.01 for HHT 200 ng/ml). HHT exerted a synergistic effect with IFN
      alpha, Ara-C and IFN-alpha + Ara-C in inhibiting CML-CP colony growth; the same
      activity was demonstrated by the combination of HHT with Ara-C and by the triple
      combination, but not by HHT + IFN-alpha, on normal myeloid progenitors. The
      triple combination only was able to exert a synergistic effect in CML-BP. The
      induction of apoptosis resulted HHT dose-dependent in CML-CP and normals; at
      higher drug concentrations (100-200-1000 ng/ml), HHT induced a significant
      increase of apoptotic cells (for normals: P = 0.04, P = 0.02 and P = 0.04; for
      CML-CP: P = 0.01, P = 0.01 and P = 0.04, respectively); no significant changes
      were observed in CML-BP. In conclusion, the differences in cytotoxic effect and
      apoptosis induction observed, depending on the various phases of CML, add
      experimental evidence to the different clinical results between the chronic
      phase, where the clone is responsive to HHT, and the acute phase, where the drug
      is ineffective. The in vitro synergism of HHT with Ara-C and IFN-alpha in CML-CP
      suggests further evaluation in the clinical setting.

PMID- 9180284
TI  - Follow-up of residual disease using metaphase-FISH in patients with acute
      lymphoblastic leukemia in remission.
AB  - Metaphase-FISH (fluorescence in situ hybridization) was used to detect cells with
      a chromosomal trisomy and/or translocation in 25 patients with acute
      lymphoblastic leukemia (ALL) in remission. Twelve patients were treated with
      chemotherapy alone and 13 patients received bone marrow transplantation after
      initial chemotherapy. Patients were followed up for 8-56 months (median 18
      months). In this study, a total of 82 bone marrow samples were analyzed.
      Metaphase-FISH identified chromosome morphology, even banding, in cells from
      which FISH signals were studied. Thus, it is as reliable as standard karyotype
      analysis and does not cause false positive results. Furthermore, more than 1000
      cells can be analyzed in 3-6 h which equals the time it takes to analyze 20
      metaphases by standard karyotype. The time span before the first positive sample
      seems to be insignificant with regard to the outcome of relapse. All six
      patients, who had more than 1% of abnormal cells detected at any sampling or
      whose consecutive follow-up samples showed an increasing frequency (up to 1%) of
      abnormal cells, relapsed. Absence or occurrence of low numbers of abnormal cells
      at a frequency of 0.05-0.8% followed by their disappearance was in agreement with
      continuing complete clinical and hematologic remission (CR) in 16 (84%) of 19
      patients. Our results indicate that metaphase-FISH is a reliable technique for
      quantifying residual leukemic cells. The technique is available in standard
      cytogenetic laboratories and can be applied to routine follow-up of ALL patients
      who have a suitable chromosomal aberration.

PMID- 9180285
TI  - Prognostic significance of WT1 gene expression at diagnosis in adult de novo
      acute myeloid leukemia.
AB  - We examined the presence of WT1-specific mRNA in bone marrow samples of 125
      patients with de novo acute myeloid leukemia at diagnosis by two-step RT-PCR. The
      sensitivity of the assay was 1:100 (first step) and 1:10000 (second step),
      respectively. WT1-specific mRNA was detected in 73% of patients. No correlation
      was found between WT1 gene expression and age, FAB type, LDH and karyotype at
      diagnosis. All patients were treated with standard induction chemotherapy. There
      was no difference in the CR rate between WT1-positive and -negative patients.
      Using Kaplan and Meier plot analysis we found no difference in disease-free
      survival (DFS) and overall survival (OS) between patients displaying the WT1
      transcript and WT1-negative patients. Furthermore, no significant interactions
      between WT1 PCR results and age, FAB type, LDH and karyotype on DFS and OS were
      demonstrable using Cox regression analysis. Eight patients who were WT1 PCR
      positive at diagnosis and achieved complete hematological remission following
      chemotherapy were monitored during the course of the disease. Based on our
      limited data demonstrating a heterogeneity of WT1 PCR results in CR we cannot
      draw any conclusions regarding the usefulness of WT1 PCR analysis for the early
      detection of relapse. We conclude that WT1 gene expression at diagnosis is not
      associated with specific characteristics of AML blast cells and is not a
      prognostic factor for CR, remission duration and overall survival in acute
      myeloid leukemia.

PMID- 9180286
TI  - Detection of CBFbeta/MYH11 fusion transcripts in acute myeloid leukemia:
      heterogeneity of cytological and molecular characteristics.
AB  - Pericentric inversion of chromosome 16, translocation (16;16) and del(16q),
      resulting in a chimerical fusion of CBFbeta and MYH11 genes, are typically seen
      in the M4Eo French-American-British (FAB) classification subset of acute
      myelogenous leukemia (AML). In this study, we analyzed 70 cases of acute non
      lymphoblastic leukemia, mainly of the M4 or M5 type. We report the very unusual
      presence of the t(16;16) and CBFbeta/MYH11 fusion transcript in an M7 patient.
      Ten M4Eo and four non-M4Eo patients presented an inv(16), t(16;16) or
      CBFbeta/MYH11 fusion transcript. In most cases, the common 'A-type' CBFbeta/MYH11
      fusion transcript was detected. In addition to the eight different breakpoints
      and the three alternative splicing variants already described, evidence of a new
      CBFbeta/MYH11 fusion transcript was found which involves a 785-bp deletion of
      MYH11. Moreover, two patients had an unusual transcript, to our knowledge only
      observed once. Only one patient had abnormal eosinophilic differentiation without
      chromosome 16 cytogenetic abnormalities or detectable CBFbeta/MYH11 fusion.
      Conversely, only one patient presented CBFbeta/MYH11 fusion without abnormal
      eosinophilic differentiation. Altogether, our data suggest a correlation between
      the CBFbeta/MYH11 fusion transcript and characteristic abnormal eosinophilic
      differentiation, whatever the FAB subtype or the percentage of abnormal
      eosinophils

PMID- 9180287
TI  - Morphological subtyping of acute myeloid leukemia with maturation (AML-M2):
      homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic
      of AML-M2 with t(8;21).
AB  - Morphologic and cytochemical features of 30 acute myeloid leukemia subtype M2
      (AML-M2) patients with t(8;21) were compared with those of 50 AML-M2 patients
      without t(8;21). It was disclosed that irregular nuclear shape, Auer bodies, and
      at least 90% myeloperoxidase positivity in blast cells, and pseudo-Pelger-Huet
      anomaly of the nuclei and homogeneous pink-colored cytoplasm of mature
      neutrophils were observed in 90-100% of the t(8;21)+ patients. The percentages of
      patients showing these features were significantly (P < 0.01) lower in the
      t(8;21)- group. Among these morphological features, homogeneous pink-colored
      cytoplasm of mature neutrophils is most characteristic of t(8;21)+ AML-M2,
      because it was seen in 90% of the t(8;21)+ patients but in only 2% of the t(8;21)
      patients. Conversely, pale-colored cytoplasm without any granules in mature
      neutrophils or dyserythropoietic features was observed in 84% of the t(8;21)-
      patients, but in none of the t(8;21)+ patients. These data suggest that it is
      possible to subtype AML-M2 patients morphologically by the recognition of
      homogeneous pink-colored or pale-colored cytoplasm of mature neutrophils and
      dyserythropoietic features. Thus, the morphologic subtyping of AML-M2 can be
      utilized alone or in combination with chromosomal or molecular subtyping for
      biological and clinical studies of AML with maturation.

PMID- 9180288
TI  - Incidence and role of apoptosis in myelodysplastic syndrome: morphological and
      ultrastructural assessment.
AB  - By application of morphological and ultrastructural methods for identification of
      apoptosis, we analyzed the incidence of morphologically evident apoptosis in the
      bone marrow of 30 patients with myelodysplastic syndrome (MDS), and in the bone
      marrow of 12 healthy individuals. According to FAB classification, out of 30
      patients, eight (26.6%) had refractory anemia, three (10%) had refractory anemia
      with ringed sideroblasts, 14 (46.6%) had refractory anemia with excess of blasts
      and two (6.8%) had refractory anemia with excess of blasts in transformation.
      Three patients (10%) had chronic myelomonocytic leukemia. Cells in apoptosis were
      examined on semithin slides and expressed as the apoptotic index (AI) (percent
      counted on at least 1000 cells). An overall increase in apoptosis in patients
      with MDS was found (median AI in patients vs controls, 3.13% vs 1.05%, P < 0.01
      by Mann-Whitney U test). Also, negative correlation between AI and white blood
      cell count was found (linear r= -0.53, or Spearman rank R= -0.52, both P < 0.01).
      In patients with evident karyotype changes AI was not higher than in patients
      with normal karyotype. This suggests that discrete alterations in apoptosis are
      present even in karyotypically 'normal' clones. Our results strongly support the
      hypothesis that apoptosis has a role in ineffective hematopoiesis and may be a
      mechanism responsible for the paradox of hypercellular bone marrow and peripheral
      blood pancytopenia in MDS.

PMID- 9180289
TI  - Clonality analysis as a tool to study the biology and response to therapy in
      myelodysplastic syndromes.
AB  - We examined the bone marrow of 45 patients with MDS at the time of diagnosis and
      in the course of the disease by means of Southern blot analysis and cytogenetic
      studies to detect and evaluate clonal markers and their implication on the
      prognosis of the disease and the response to treatment. All patients were
      enrolled in an EORTC study and received low-dose Ara-C with or without growth
      factors according to the study protocol. Thirty patients (67%) were characterized
      by different clonal markers, such as various gene rearrangements (eg Ig-JH, tcR
      beta, bcr, GM-CSF, G-CSF or IL-3) and/or chromosomal markers at the time of
      diagnosis or early in the course of the disease. In 23 of 30 cases that could be
      studied in the course of the disease, a statement about the clonal situation was
      possible: in three cases (8%) the clonal situation did not change, in nine cases
      (39%) at least a transient reduction of clonal cells could be demonstrated,
      suggesting partial or complete response to therapy. In eight cases (35%) a change
      for the worse could be seen. In four cases (17%) involvement of multiple clones
      could be demonstrated with the clones exhibiting different susceptibilities to
      treatment. Clinical evaluation showed that patients without clonal markers at
      diagnosis had a better prognosis as compared to patients who presented with
      clonal markers. We suggest that clonality analysis at diagnosis and in the course
      of the disease will be a useful tool to study the biology and response to
      treatment in MDS.

PMID- 9180290
TI  - All-trans retinoic acid potentiates the inhibitory effects of interferon alpha on
      chronic myeloid leukemia progenitors in vitro.
AB  - All-trans retinoic acid (ATRA) has recently been shown to synergize with the
      inhibitory effect of interferon alpha (IFN alpha) on the growth of malignant
      cells isolated from solid tumors. We investigated whether ATRA could potentiate
      the inhibitory effects of IFN alpha on the proliferation of leukemic progenitors
      in chronic myeloid leukemia (CML). CD34+ cells from chronic phase, newly
      diagnosed patients, were incubated in short-term liquid culture with ATRA, IFN
      alpha or a combination of both molecules and then plated on semi-solid cultures
      for colony-forming cell assay. IFN alpha was found to inhibit preferentially the
      generation of late progenitors. ATRA at a concentration of 10(-8) M was found
      strongly to inhibit CFU-M colonies. Addition of ATRA to IFN alpha dramatically
      potentiated the inhibitory effects of INF alpha on CFU-GM growth. In the presence
      of both molecules the inhibition of day 14 CFU-GM from CD34+ cells was lowered to
      27 +/- 4% of control. CFU-M colonies were completely inhibited. RT-PCR analysis
      of the colonies resulting from the action of the combination IFN alpha plus ATRA
      showed the presence of an increased number of BCR-ABL-negative colonies
      relatively to what was observed with IFN alpha alone. FISH analysis showed a
      higher percentage of Ph-negative cells in the ATRA plus IFN alpha-treated
      samples, confirming PCR experiments. These results indicate that, in vitro, the
      combination of IFN alpha and ATRA effectively inhibits CFU-GM colony formation in
      CML and suggest that it has a potential interest for the treatment of CML.

PMID- 9180291
TI  - Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the
      expression of CD38 and CD117.
AB  - It has been supposed in de novo AML that malignant transformation occurs at the
      level of committed progenitors. Recent data of our group and others provide
      evidence that in AML malignant transformation may regularly occur at the level of
      stem cells. These cells can be discriminated by function and specific surface
      molecules. CD34, a glycophosphoprotein, is a cellular surface antigen
      characteristically expressed by stem cells. CD34+ stem cells can be further
      subdivided by the expression of additional surface molecules like CD38 and CD117.
      In this article we present results from cytogenetic examinations of FACS-isolated
      stem cell subpopulations in eight patients (four AML and four MDS). Six of them
      displayed clonal karyotype abnormalities at the time of first diagnoses in the
      native bone marrow (5q-; 5q- and complex abnormalities; +8; inv(16) and +8;
      i(17q) and -21; i(21q)). We used CD117, the receptor for the stem cell factor
      (also KIT oncogene) as a new cellular surface marker. CD34+/CD117+/- stem cell
      subpopulations were examined in two patients with AML and three patients with
      MDS. We found leukemic stem cells in every type of stem cell subpopulation
      examined (CD34+/CD38-, CD34+/CD38+, CD34+/CD117-, CD34+/CD117+). Secondary,
      progression-associated chromosome abnormalities likewise were demonstrable in
      CD34+ cells. In three patients a mosaic of normal and abnormal metaphases was
      found in the highly purified stem cell subpopulations. We conclude that in AML
      and MDS stem cells are the target of leukemogenic genetic defects. CD117 as a new
      marker to isolate different CD34+ subpopulations was not sufficient to
      discriminate between normal and leukemic stem cells. Our findings have
      implications for autologous stem cell transplantation, high-dose chemotherapy and
      the pathogenetic concept of leukemogenesis.

PMID- 9180292
TI  - The combined effects of IL-3 and PSC 833 on daunorubicin- and mitoxantrone
      cytotoxicity in two growth factor-dependent leukemic cell lines.
AB  - In the present study it was investigated whether and by which mechanisms the co
      administration of interleukin-3 (IL-3) and the P-glycoprotein blocker PSC 833 can
      augment mitoxantrone (MX) and daunorubicin (DAU) cytotoxicity in two human growth
      factor dependent P-glycoprotein (P-gp) positive myeloid leukemic cell lines, Mo-7
      and GF-D8. Cytotoxicity was determined in MTT assay. Increased cytotoxicity
      occurred in Mo-7 cells preincubated with 24h IL-3 followed by 1 h MX (cell
      survival: 85% +/- 6 vs 68% +/- 2, at 0.05 microM MX, P < 0.005) or DAU (79% +/- 8
      vs 62% +/- 9 at 0.8 microg/ml DAU, P < 0.05). Similar results were obtained for
      the GF-D8 cell line. In this cell line, at 0.5 microM MX the cell survival
      decreased from 84% +/- 13 to 61% +/- 19 (P < 0.05) and at 5.0 microg/ml DAU from
      102% +/- 8 to 69% +/- 5, (P < 0.002). The IL-3 administration did not affect the
      P-gp and bcl-2 protein expression, cellular MX concentration or MX efflux but
      coincided with an increased percentage of cells in S-phase and topoisomerase II
      (topo II)-alpha mRNA and topo II activity especially in the Mo-7 cell line. PSC
      833 enhanced DAU cytotoxicity in both cell lines. The administration of IL-3 plus
      PSC 833 in the Mo-7 cell line resulted in an additive effect on DAU cytotoxicity.
      At 0.8 microg/ml DAU and 2 microg/ml PSC 833, the percentage surviving cells
      decreased from 62% +/- 9 in the absence of IL-3 to 37% +/- 3 in the presence of
      IL-3 (P < 0.01). The additive effect of combined treatment was most pronounced in
      GF-D8 cells which also had the highest P-gp expression. In contrast, PSC 833 did
      not modulate the MX effects, irrespective of the presence of IL-3. In summary,
      the results demonstrate that the combined administration of IL-3 and PSC 833 can
      enhance the cytotoxic effects of DAU but not MX in these P-gp positive cell lines
      whereas the effects of MX could be modulated by factors which influence topo II
      activity.

PMID- 9180293
TI  - Human/mouse radiation chimera generated from PBMC of B chronic lymphocytic
      leukemia patients with autoimmune hemolytic anemia produce anti-human red cell
      antibodies.
AB  - Previous studies performed in our laboratory have shown that B-CLL cells are
      involved in the production of anti-red cell auto-antibodies, providing a possible
      mechanism for the autoimmune hemolytic anemia occurring during the course of B
      CLL. In order to confirm this hypothesis, we attempted to transfer human B-CLL
      with AIHA to immunodeficient mice. Peripheral blood mononuclear cells (PBMC) from
      11 B-CLL patients suffering from AIHA were transplanted into the peritoneal
      cavity of lethally irradiated Balb/c mice reconstituted with SCID bone marrow.
      Chimeric mice generated from PBMC of these patients (in stage III-IV of the
      disease) exhibited an engraftment profile with dominance of tumor cells and
      minuscule levels of T cells. Eighty-five percent of the chimeric mice generated
      from 10 out of the 11 B-CLL patients with Coombs'-positive AIHA, produced human
      Ig with anti-human red cell specificity as detected by indirect anti-globulin
      test. In addition, anti-red cell auto-antibodies were produced in 36% of chimeric
      mice generated from PBMC of Coombs'-negative B-CLL. In contrast, control
      experiments in which splenic cells from idiopathic AIHA or PBMC from normal
      donors were transplanted, failed to produce anti-RBC. This in vivo model further
      supports the relationship between the B cell expansion and the autoimmune
      hemolytic process.

PMID- 9180294
TI  - Regulation of BCL-6 gene expression in human myeloid/monocytoid leukemic cells.
AB  - We demonstrated in the present study that the BCL-6 transcripts were detectable
      not only in B cells, but also in circulating granulocytes and monocytes from
      normal individuals, and in human acute nonlymphocytic leukemia cells of certain
      subtypes (M3, M4, M5). Then, with an assumption that the BCL-6 gene expression
      may be related to the differentiation of myeloid cells, we analyzed the
      inducibility of BCL-6 gene expression along monocytic lineage differentiation in
      HL-60 and U-937 cells by treating them with 12-O-tetradecanoylphorbol-13-acetate
      (TPA). Although the expression of BCL-6 transcripts was very low or undetectable
      in untreated HL-60 or U-937 cells, treatment of these cells with TPA to induce
      monocytic differentiation resulted in an apparent increase of BCL-6 mRNA,
      suggesting that BCL-6 gene expression is not limited to B cells and it is closely
      associated with monocytic lineage differentiation. The BCL-6 transcripts in TPA
      treated U-937 cells were superinduced by the treatment with cycloheximide (CHX)
      and the half-life of the BCL-6 mRNA was apparently prolonged when TPA-treated U
      937 cells were exposed to CHX in the presence of actinomycin D (ACD).
      Furthermore, the nuclear run-on assay revealed that the BCL-6 transcription
      signals were enhanced by TPA treatment. These results suggest that the increase
      of BCL-6 mRNA in U-937 cells stimulated with TPA to induce monocytic lineage
      differentiation is mediated by both transcriptional and post-transcriptional
      regulation.

PMID- 9180295
TI  - Cytokine response profiles of human myeloid factor-dependent leukemia cell lines.
AB  - Research in cytokine biology has grown exponentially in recent years as cytokines
      (often also termed growth factors) are now known to be involved in a wide range
      of pathological and physiological processes. Continuous human leukemia cell lines
      represent powerful tools to investigate these mechanisms. Most cell lines grow
      autonomously in standard culture media (containing fetal bovine serum)
      independent of externally added growth stimuli. Over the last 5-10 years a
      battery of myeloid leukemia-derived cell lines has been established that is
      constitutively dependent on the addition of cytokines to the culture. Such factor
      dependent cell lines die rapidly by apoptosis when deprived of the appropriate
      growth factor. We determined the cytokine response profiles of 19 absolutely
      growth factor-dependent leukemia cell lines with myelomonocytic, erythroid or
      megakaryocytic phenotypes with regard to enhanced or suppressed cellular
      proliferation. Cells were incubated in liquid culture with optimal concentrations
      of various recombinant human cytokines known to have effects on the growth of
      hematopoietic cells. A proliferative or anti-proliferative response to these 41
      cytokines was assessed by the short-term 3H-thymidine uptake assay. A
      proliferative response was considered as positive when the stimulation index (SI)
      was >2; inhibition was regarded as significant with an SI <0.5. The response
      profile of each cell line to these 41 cytokines was different and individual.
      None of the cell lines responded to one or two factors only (minimum to at least
      five cytokines). Proliferation of most (n = 13-17), but not of all cell lines was
      significantly enhanced by GM-CSF, IL-3, PIXY-321, SCF and IFN-gamma. TGF-beta1
      consistently inhibited proliferation (in 11/19 cell lines). IFN-alpha, IFN-beta,
      TNF-alpha and TNF-beta had either stimulatory or inhibitory effects. The cell
      lines responding most often proliferatively (to 15-19 different cytokines) were
      UCSD/AML1, HU-3, TF-1 and M-07e. In summary, these factor-responsive human
      leukemia cell lines represent extremely useful model systems for the analysis of
      cytokine effects on hematopoietic cells. The cytokine response profiles of the
      individual cell lines provide guidelines for the selection of the appropriate
      cell culture for such experiments.

PMID- 9180297
TI  - In vitro study using leukemia cell line panel to demonstrate rapid thymic T cell
      death due to contact with HIV-1 carrier cell clones.
AB  - A rapid (within 1 h) and profound cytotoxic cell death of immature TdT+CD4+CD8+
      and/or TdT+CD4+ thymic T cell type leukemia cell lines, and of normal thymocyte
      populations rich in TdT+CD4+CD8+ cells was induced by contact with some human
      immunodeficiency virus type-1 (HIV-1) carrier T cell clones. This cytotoxic
      reaction, without requiring a complete viral replication cycle in the thymic T
      cells, did not occur in any mature CD4+CD8+ and/or CD4+ T cells which are
      otherwise permissive for virus infection. Although it was not an antigen-specific
      cytotoxic reaction, the rapid and profound thymic T cell destruction was shown,
      at the individual clonal level, to be triggered specifically by the binding of
      CD4 molecules on thymic T cells with gp120/gp160 on HIV-1 carrier clones. The
      present study suggesting direct elimination of immature T cells by contact with
      some HIV-1-infected T cells, may provide a novel insight into the mechanism
      responsible for the mature CD4+ T cell depletion in HIV-1 infection.

PMID- 9180296
TI  - Establishment and characterization of a new, factor-independent acute myeloid
      leukemia line designated Ei501.
AB  - We established a factor-independent acute myeloid leukemia cell line, designated
      Ei501. The line has been growing in RPMI 1640 media for 18 months and can be
      maintained without addition of growth factors. Ei501 is positive for
      myeloperoxidase and negative for esterase and PAS. Cytogenetic analysis revealed
      the FAB M3 associated t(15;17) translocation and a translocation of the
      chromosomes 7 and 8: 46 XX, -7, +t(7;8)(q32;q13), t(15;17)(q22;q12). This
      karyotype was confirmed by fluorescence in situ hybridization. Ei501 cells
      express AML-associated surface markers such as CD13, CD33 and CD38. Although 42%
      of the patient's blast cells were CD34-positive, the line lacks surface
      expression of CD34. Furthermore the line has a number of characteristics which
      are detectable in blasts from AML patients, such as surface adhesion molecules,
      cytokines such as TGF-beta, cytokine receptors such as the IL-2 receptor beta and
      gamma chains or the IL-4 receptor and the genes for the transcription factor wt-1
      (Wilms' tumor gene) and for the proto-oncogene bcl-2, both shown to be present in
      the majority of patients with AML. Additionally the line can be used as target in
      cytotoxicity assays using IL-2 activated cytotoxic lymphocytes as effector cells.
      In conclusion, besides a rare karyotype the Ei501 cell line has several features
      common in AML, and may therefore be used as a model to study pathogenetic
      mechanisms in acute myeloid leukemia.

PMID- 9180298
TI  - Autologous bone marrow purging by in situ IL-2 activation of endogenous killer
      cells.
AB  - The major cause of treatment failure in hematologic malignancies is the
      development of resistance to chemotherapeutic agents and the presence of
      clonogenic tumor cells in remission bone marrow. In the present study, we tested
      the optimal conditions for activation by interleukin-2 (IL-2) of endogenous bone
      marrow effector cells to develop cytotoxicity against solid tumor and leukemia
      cells and the effects of IL-2 treatment on eradication of malignant cells from
      the marrow product while preserving hematopoiesis. Normal donor bone marrow was
      contaminated with 10% A549 lung cancer cells, MCF-7 breast cancer, or EM2
      leukemia cells, and then combined with peripheral blood-derived lymphokine
      activated killer (LAK) cells which had been incubated in the presence of IL-2,
      6000 IU/ml, for 5 days. Eradication (A549 and MCF-7) or >90% reduction in tumor
      cell number (EM2) was achieved upon exposure of the marrow to LAK cells but not
      to control, non-IL-2-exposed PBMC. The non-cross-resistance of chemotherapy and
      cell-mediated cytotoxicity were tested by using chemoresistant target cells for
      LAK cytotoxicity assays. Ara-C-resistant K562 cells were sensitive to LAK
      cytotoxicity, similar to sensitive controls. Similar effects were seen in
      daunomycin-resistant HL60 leukemia cells and VP-16-resistant K562 cells. The
      daunomycin-resistant K562 cells were also sensitive to LAK cell killing similar
      to sensitive controls. Activation of bone marrow mononuclear cells (BMMC) with IL
      2, 6000 IU/ml for 24 h, significantly enhanced cytotoxicity against the NK
      resistant, LAK-sensitive Daudi cell line. This procedure did not result in
      significant loss of total BMMC or hematopoietic colony-forming units. We then
      studied the possibility that the effector cell activity of the IL-2-activated
      BMMC which is diminished after removal of the IL-2 at 24 h could be recovered
      upon re-exposure of the marrow to IL-2. We found that the optimum conditions for
      preserving cytotoxicity were prolonged continuous exposures to IL-2 but that re
      exposure of the 24-h IL-2-activated BMMC to IL-2 after a 1- or 2-week IL-2
      withdrawal was associated with full recovery of cytotoxicity. These experiments
      also demonstrated that the overall recovery of viable cells from the BMMC was
      over 100%, possibly due to a proliferative effect of the IL-2 exposure on BMMC.
      These results demonstrate that the use of IL-2-activated marrow in patients with
      acute leukemia in remission undergoing autologous bone marrow transplantation
      (aBMT) may overcome the obstacles of clonogenic, drug-resistant minimal residual
      disease. The effector cell activity and hematopoietic capacity of the activated
      bone marrow product can also be maintained even if optimal clinical care requires
      an interruption in the in vivo exposure to IL-2. This therapeutic approach is
      currently being tested in acute leukemia patients undergoing IL-2-activated aBMT
      followed by prolonged IL-2 treatment before and after hematologic reconstitution.

PMID- 9180299
TI  - Infusion of donor-derived peripheral blood leukocytes after transplantation of
      cord blood progenitor cells can increase the graft-versus-leukaemia effect.
AB  - We describe the case of a child affected by acute lymphoblastic leukaemia who
      received adoptive immunotherapy after cord blood transplantation (CBT). The
      patient, transplanted in second relapse resistant to chemotherapy, still showed
      lung and costal leukaemic nodular lesions 2 months after CBT. For this reason,
      three infusions of donor peripheral blood leukocytes 1 x 10(7)/kg each were
      administered on days +60, +80 and +100. The procedure was well tolerated by both
      patient and donor, and a complete disappearance of the lung lesions was
      documented 2 months after the last infusion. The patient remains in continuous
      complete haematological remission 13 months after CBT. This experience suggests
      that adoptive immunotherapy may be safely employed after CBT in order to increase
      the contribution of immune-mediated anti-leukaemia effect.

PMID- 9180300
TI  - Establishment of multipotential and antigen presenting cell lines derived from
      myeloid leukemias in GM-CSF transgenic mice.
AB  - In this study neonatal mice expressing a GM-CSF transgene (GMT mice), and their
      normal littermate controls, were infected with Moloney murine leukemia virus
      (MoMLV) to examine in vivo tumorigenesis. By 200 days, all of the GMT mice had
      died whereas median survival had not been reached in the littermates (P <
      0.0003). Thymomas developed in 32% of GMT mice and were more frequently CD4+CD8+
      (83%) compared to the CD4+CD8- phenotype seen in 90% of thymomas developing in
      MoMLV-infected littermate mice. A primitive myeloid leukemia was induced in 21%
      of GMT mice, but none of the littermates. To characterize further the nature of
      the leukemic cells, a factor-dependent cell line (DGM36) was derived. DGM36 cells
      were tumorigenic, capable of differentiation to neutrophils, macrophages and
      eosinophils, and contained a partial deletion of chromosome 2. A subline arose
      spontaneously that was factor-independent and produced GM-CSF in an autocrine
      manner (IGM36 cells). Stimulation of the IGM36 cells with TNF alpha and IFNgamma
      resulted in increased expression of B7-1, class I MHC and class II MHC and
      consequent presentation of antigen in allogeneic MLRs. IGM36 cells thereby
      satisfy many of the criteria of dendritic cells and consequently may be used to
      examine antigen presentation by leukemic cells. This is the first report of
      primary myeloid leukemias arising in GMT mice and documents the derivation of a
      multipotential, autocrine leukemic cell line with dendritic cell characteristics.

PMID- 9180301
TI  - Predominance and characteristics of Burkitt lymphoma among children with non
      Hodgkin lymphoma in northeastern Brazil.
AB  - The purpose of this paper was to define the histologic distribution, clinical
      features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in
      northeastern Brazil. We reviewed medical records and histopathologic studies of
      98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center
      in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden
      (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent
      chemotherapy). There was a striking predominance of the small noncleaved cell
      (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents
      diagnosed with NHL. Subsequent analyses focused on these patients. The majority
      (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the
      most common site of disease (84 cases); jaw involvement was rare (three cases).
      Five-year event-free survival (excluding treatment refusals) was significantly
      better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/-
      6%; P < 0.04). Elevated serum LDH (>500 U/l) was associated with a poorer outcome
      (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of
      patients are long-term survivors, reflecting the high rate of septic deaths (25%
      of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr
      virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In
      clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in
      their apparent responsiveness to LSA2L2 therapy and association with EBV, they do
      not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt
      subtype, and is associated with clinical features that appear to distinguish it
      from the endemic and sporadic forms of this tumor. These cases may represent a
      third or intermediate subtype of Burkitt lymphoma.

PMID- 9180302
TI  - Characteristic pattern of chromosomal gains and losses in marginal zone B cell
      lymphoma detected by comparative genomic hybridization.
AB  - Marginal zone B cell lymphoma (MZBCL) represents a distinct subtype of B cell non
      Hodgkin's lymphoma, which has been recently recognized and defined as a disease
      entity. We investigated 25 cases (18 at primary diagnosis and seven during the
      course of disease) of MZBCL by comparative genomic hybridization (CGH) and
      compared these results with cytogenetic, fluorescence in situ hybridization
      (FISH), and Southern blot data. Twenty of the 25 cases (80%) showed gains (total
      49) or losses (total 15) of genetic material. In extranodal, nodal, and splenic
      MZBCL, material of chromosomes 3 (52% of cases), 18 (32%), X (24%), and 1q (16%)
      was most frequently gained, whereas losses predominantly involved chromosomes 17
      (16%) and 9 (12%). High-level amplifications involving the regions 18q21-23 and
      18q21-22, respectively, were detected in two cases. Gains of chromosomes 1q and
      8q and losses of chromosome 17 or 17p occurred more frequently in relapsed or
      progressive lymphomas. For all of the frequently affected chromosomes, CGH
      allowed narrowing of the relevant subregions including 3q21-23, 3q25-29 and 18q21
      23. By Southern blot analysis, the BCL2, BCL6, and CMYC proto-oncogenes were
      found to be a part of the over-represented regions in two cases, one case, and
      two cases, respectively, with gains involving 18q, 3q or 8q. In 13 cases, CGH
      revealed chromosomal imbalances which were not detected by cytogenetic analysis
      but could be confirmed by FISH or Southern blot analysis in all cases
      investigated. On the other hand, CGH failed to detect trisomy 3, trisomy 18, and
      deletion 7q in three cases with a low proportion of tumor cells bearing these
      abnormalities, as shown by interphase FISH. The characteristic pattern of
      chromosomal gains and losses detected in this study confirms the distinct nature
      of MZBCL and may point to chromosomal regions involved in the pathogenesis of
      these neoplasms.

PMID- 9180303
TI  - T cell receptor Ddelta2Ddelta3 rearrangement: a suitable allele-specific marker
      for the detection of minimal residual disease in childhood acute lymphoblastic
      leukemia.
AB  - The applicability of T cell receptor (TCR) Ddelta2Ddelta3 junctional regions for
      the detection of minimal residual disease (MRD) was examined in childhood acute
      lymphoblastic leukemia (ALL). Southern blot analysis showed a Ddelta2Ddelta3
      rearrangement in 22 of 172 (13%) precursor-B ALL. No Ddelta2Ddelta3 rearrangement
      was identified in 29 T-ALL cases. Three patients exhibited Ddelta2Ddelta3
      recombinations in both alleles. Sequence analysis of Ddelta2Ddelta3 junctions
      revealed extensive diversity due to the random insertion and deletion of
      nucleotides at the joining site. PCR analysis utilizing allele-specific probes or
      oligonucleotides generated on the basis of Ddelta2Ddelta3 junctional sequences
      reached a sufficient sensitivity of 10(-4) to 10(-5) in the majority of cases. In
      four of 25 (16%) rearranged alleles, however, the 5' heptamer-nonamer
      recombination signal sequence (RSS) of the Ddelta2 segment had recombined
      directly to the 3' heptamer-nonamer RSS of the Ddelta3 segment thus generating a
      so-called signal junction. Respective heptamer-heptamer junctions are not suited
      to design allele-specific oligonucleotides for the detection of MRD because of
      their limited diversity and hence specificity.

PMID- 9180304
TI  - True histiocytic lymphoma: is it an entity?
AB  - Monocytes and macrophages are closely related in origin, structure and function.
      True histiocytic lymphoma is a neoplasm of phagocytic histiocytes and is treated
      as non-Hodgkin's lymphoma. Tissue involvement with myeloid leukemia, including
      monocytic leukemia, is called extramedullary myeloid cell tumor or granulocytic
      sarcoma and treated with antileukemic chemotherapy. Differentiating true
      histiocytic lymphoma from tissue involvement with monocytic leukemia is a rather
      impossible task using available morphologic, cytochemical, immunocytochemical and
      molecular methods. The two entities need to be unified probably more
      appropriately as extramedullary myeloid cell tumor of monocytic origin, and
      should therefore be treated as such.

PMID- 9180305
TI  - Hypereosinophilic syndrome or chronic eosinophilic leukemia: report of a case
      with a lytic bone lesion.
AB  - Some cases of hypereosinophilic syndrome and myeloproliferative disorders exhibit
      common features and thus pose diagnostic and therapeutic problems. We describe a
      68-year-old patient who presented with such features and developed lytic lesion
      in the tibia. Based on our case and a review of literature we suggest that cases
      like ours should be classified and treated as chronic eosinophilic leukemia (a
      myeloproliferative disorder) rather than as a hypereosinophilic syndrome or as an
      atypical chronic myeloid leukemia.

PMID- 9180306
TI  - Emergence of new clonal abnormalities following interferon-alpha induced complete
      cytogenetic response in patients with chronic myeloid leukemia: report of three
      cases.
AB  - New treatments which may change the course of a disease, or which have potential
      carcinogenicity, may result in the development of new cytogenetic or clinical
      disorders. Three patients with Philadelphia chromosome-positive (Ph-positive)
      chronic myeloid leukemia (CML) who developed new cytogenetic abnormalities after
      achieving a cytogenetic complete remission (CR) of their Ph-positive disease with
      interferon alpha (IFN-alpha) based therapy are described. Patient 1 developed
      chromosomal abnormalities involving chromosomes 5 (5q13-34) and later 7 (monosomy
      7) 60 months after the start of therapy and 20 months after IFN-alpha was
      discontinued. A myelodysplastic syndrome was noted 83 months from the start of
      therapy. Patient 2 developed a myeloproliferative syndrome with 18p11 chromosomal
      abnormalities 90 months after the start of the therapy and 60 months after IFN
      alpha was discontinued. Patient 3 developed a chromosome 11 abnormality (11q21
      23) 23 months after the start of therapy, without hematological manifestations.
      All three patients remain in cytogenetic CR of Ph-positive disease with the
      hypermetaphase fluorescent in situ hybridization and polymerase chain reaction
      studies for BCR/ABL showing minimal residual disease. The emergence of new
      cytogenetic or clinical disorders in patients with CML on IFN-alpha therapy needs
      to be monitored. These findings may be related to changing the natural course of
      CML, to therapy, or to the emergence of suppressed clones in a stem cell
      disorder.

PMID- 9180307
TI  - Highly complex chromosomal abnormalities in plasma cell leukemia as detected by
      FISH technique.

PMID- 9180308
TI  - Radiological and survival comparison of four methods of fixation of a proximal
      femoral stem.
AB  - We compared the radiological appearances and survival of four methods of fixation
      of a femoral stem in 538 hips after follow-up for five or ten years. The fixation
      groups were: 1) press-fit shot-blasted smooth Ti-A1-V stem; 2) press-fit shot
      blasted proximally ridged stem; 3) proximal hydroxyapatite (HA) coating; and 4)
      cementing. Survival analysis at five to ten years showed better results in the HA
      coated (100% at five to six years) and cemented stems (100% at 5 to 6 years) than
      in the two press-fit groups. There was a higher mean rate of migration in the
      smooth and ridged Ti-A1-V shot-blasted press-fit groups (0.8 mm/year and 0.6
      mm/year, respectively) when compared with the HA-coated and cemented prostheses
      (both 0.3 mm/year). More radiolucent lines and osteolytic lesions were seen in
      the press-fit groups than in either the HA-coated or cemented implants, with a
      trend for a lower incidence of both in the HA compared with the cemented group.
      Proximal osteopenia increased in the press-fit and cemented prostheses with time,
      but did not do so in the HA group. There was a higher incidence of resorption of
      the femoral neck with time in the cemented group than in the other three. We
      conclude that the HA and the cemented interfaces both provide secure fixation
      with a trend in favour of HA. The cemented prosthesis meets the suggested
      National Institutes of Health definition of 'efficacious' at ten years.

PMID- 9180309
TI  - Measurement of polyethylene wear in cementless total hip arthroplasty.
AB  - We made a clinical study of polyethylene wear in 240 hips of 187 patients having
      primary total hip arthroplasties from 1989 to 1990, using uncemented Osteonics
      components, with a head size of 26 mm. We excluded cups with anteversion of over
      20 degrees and measured linear wear by a new method using a digitiser and special
      software of our design. Follow-up was from two to five years (mean 4.3). The mean
      age at operation was 50.3 years, with more men than women (1.4:1). The mean
      linear wear per year was 0.15 mm; this did not increase with the longevity of the
      prosthesis (p = 0.54). In 59 hips showing evidence of osteolysis, the mean linear
      wear rate was significantly higher at 0.23 mm/year (p <0.001). The mean linear
      wear rate also correlated significantly with age at the time of operation (p =
      0.008), but we found no significant correlations with body-weight, gender,
      aetiology of the disease, thickness of polyethylene, or cup position. Our new
      method of measurement is time-saving and reproducible. The results confirm the
      greater rate of linear wear of polyethylene in patients showing osteolysis and in
      those who are younger.

PMID- 9180311
TI  - Increased awareness of glove perforation in major joint replacement. A
      prospective, randomised study of Regent Biogel Reveal gloves.
AB  - An intact barrier between the hands of the surgeon and the patient remains the
      single most important factor in protection against infection for both. Increasing
      the awareness of possible glove perforation without skin penetration will
      decrease the risk of contamination. We performed a prospective, randomised trial
      comparing the incidence of glove perforation using a new type of glove (Regent
      Biogel Reveal) and standard double-gloves in total hip and knee replacement. One
      or more perforations was detected in 14.6% of all gloves. The new gloves
      increased significantly the awareness of perforation. Multiple perforations at
      the base of the ring finger were found in surgeons who wore wedding rings during
      the operation and we recommend that rings be removed before undertaking surgery.

PMID- 9180310
TI  - Middle-term results of threaded acetabular cups. High failure rates five years
      after surgery.
AB  - We report our results using three different threaded acetabular components
      (Mecring A, Mecring B and Weill) in 715 hips with a follow-up of between one and
      ten years (median: 99.1, 56.5, 38.3 months, respectively). All cups were
      implanted with one type of cementless stem. The clinical results were good or
      acceptable in about 70% of the hips, but signs of loosening with radiolucency
      and/or migration were found in 10.1%. Radiological evidence of loosening did not
      correlate significantly with the clinical outcome. Pain was not a reliable
      indicator of loosening and its absence sometimes allowed severe osteolysis to
      develop. Twenty-five hips were revised (3.5%) for aseptic loosening of the
      acetabular component. Kaplan-Meier estimates of the cumulative rate of failure
      showed a rapid increase five years after the initial operation, but no
      significant correlation with gender, age or weight. The high rate of failure
      indicates that further use of these acetabular components cannot be recommended.
      Annual radiographs are required to assess osteolysis even if the patients are
      free from pain.

PMID- 9180312
TI  - The prognosis and treatment of dislocated total hip arthroplasties with a 22 mm
      head.
AB  - We studied the risk of recurrent dislocation in 121 primary and 39 revision
      Charnley or Charnley hybrid total hip arthroplasties which had been treated for a
      primary dislocation between 1979 and 1995. Only 35% of these hips had no further
      dislocation or a revision for instability within one year. The rates of survival
      gradually declined with time or if a second, third or fourth dislocation
      occurred. The risk of recurrence was greater in men, but was not related to age,
      diagnosis, time of the first dislocation or whether the index operation had been
      a primary or a revision procedure. Operative treatment included 15 reoperations
      leaving intact components, 50 revisions, and permanent removal of the femoral
      stem in seven patients. The operation was successful in four patients with
      reoperations and in 36 who had an exchange procedure within two years. Treatment
      was successful in 35 of 49 hips in which it was possible to correct a technical
      error compared with 5 out of 16 hips in which malposition of the components was
      not seen (p = 0.007).

PMID- 9180313
TI  - Cement pressurisation during hip replacement.
AB  - The newer techniques of cementing aim to improve interlock between cement and
      bone around a femoral stem by combining high pressure and reduced viscosity. This
      may produce increased embolisation of fat and marrow leading to hypotension,
      impaired pulmonary gas exchange and death. For this reason the use of high
      pressures has been questioned. We compared finger-packing with the use of a
      cement gun by measuring intramedullary pressures during the cementing of 31 total
      hip replacements and measuring physiological changes in 19 patients. We also
      measured pressure in more detail in a laboratory model. In the clinical series
      the higher pressures were produced by using a gun, but this caused less
      physiological disturbance than finger-packing. The laboratory studies showed more
      consistent results with the gun technique, but for both methods of cementing the
      highest pressures were generated during the insertion of the stem of the
      prosthesis.

PMID- 9180314
TI  - Detection of orthopaedic prostheses at airport security checks.
AB  - We studied the detection of joint replacements at airport security checks in
      relation to their weight, using two types of detector arch. A single-source,
      unilateral detector showed different sensitivities for implants on different
      sides of a test subject. All implants weighing more than 145 g were detected by
      one of the arches. The degree of detection was directly related to the logarithm
      of the weight of the prosthesis in patients, with a linear correlation (r2 =
      0.61). A bilateral arch detected all prostheses weighing over 195 g. With their
      usual sensitivity settings many joint replacements were detectable; an
      identification pass containing the site and weight of such prostheses would help
      to avoid the need for body-search procedures.

PMID- 9180315
TI  - Detection of orthopaedic implants by airport metal detectors.
AB  - We have assessed the effect of a variety of implants commonly used in fracture
      fixation and joint replacement on the activation of metal detectors at airport
      security gates. A volunteer with metal implants strapped on and patients with
      implants in situ walked through the device. Implants used in fixation do not
      activate it, except for Richards cannulated screws. An Austin-Moore prosthesis
      does set off the detector, but a single joint replacement does not. Three or four
      joint replacements activate the alarm and patients with these implants should be
      warned of this possibility.

PMID- 9180316
TI  - Cubital tunnel reconstruction for ulnar neuropathy in osteoarthritic elbows.
AB  - We operated on 16 patients for ulnar neuropathy associated with osteoarthritis of
      the elbow. They were all male manual workers, with an average age of 51 years at
      the time of surgery. The severity of the symptoms was McGowan grade 1 in five
      patients, grade 2 in nine and grade 3 in two. The mean follow-up was 36 months.
      The operation consists of resecting the osteophytes around the postcondylar
      groove. The shallow and narrow cubital tunnel is made deep and wide and the ulnar
      nerve is replaced with its surrounding soft tissues in the enlarged groove. All
      patients were relieved of discomfort and all showed some improvement or full
      recovery of motor and sensory function. The ulnar nerve showed no evidence of
      irritation or adhesion. This procedure also allows early movement of the elbow
      after operation, because the subcutaneous tissues and muscles have not been
      detached.

PMID- 9180317
TI  - The Norway elbow replacement. Design, technique and results after nine years.
AB  - The Norway elbow prosthesis is a non-constrained cemented total replacement. It
      depends on intact collateral ligaments for stability, and allows a full range of
      movement. The system includes several sizes of components, all freely
      interchangeable, and semi-constraint can be provided by a locking ring if damaged
      collateral ligaments make dislocation possible. The prosthesis has been used in
      more than 350 elbows in Norway and the detailed results for 118 elbows studied
      prospectively since 1987 are reported. It is inserted through a posterolateral
      triceps-splitting incision with minimal muscle disruption and bone resection,
      preserving the collateral ligaments. The results as regards pain relief and range
      of movement were comparable with those of other elbow prostheses, but there were
      fewer serious complications. At a mean follow-up of 4.3 years, the failure rate
      was 3.4%.

PMID- 9180318
TI  - Limb salvage using distraction osteogenesis. A classification of the technique.
AB  - We report the results of distraction osteogenesis (callotasis) for the
      reconstruction of extensive defects after the excision of skeletal tumours in the
      limbs. Bone transport was performed in ten patients (five osteosarcomas and five
      giant-cell tumours), shortening-distraction in three (two osteosarcomas and one
      Ewing's sarcoma), and distraction osteogenesis combined with an intramedullary
      nail to reduce the time of external fixation in six (three osteosarcomas, two
      chondrosarcomas, and one malignant fibrous histiocytoma). The mean length of the
      defects after excision of the lesion was 8.4 cm. The mean external fixation index
      was 39.5 days/cm for the group treated by bone transport, 34.1 days/cm for the
      shortening-distraction group, and 24.0 days/cm for the group treated by
      distraction and an intramedullary nail. Functional evaluation gave excellent
      results in 12 patients, good in five and fair in two. There were ten
      complications in 19 patients, all of which were successfully treated. We also
      classified reconstruction using distraction osteogenesis into five types based on
      the location of the defects after resection of the tumour: type 1, diaphyseal;
      type 2, metaphyseal; type 3, epiphyseal; type 4, subarticular reconstruction; and
      type 5, arthrodesis. Our results suggest that reconstruction using distraction
      osteogenesis provides bone which will develop sufficient biomechanical strength
      and durability. It is beneficial in patients with an expectation of long-term
      survival and in growing children.

PMID- 9180319
TI  - Treatment of displaced proximal humeral fractures in elderly patients.
AB  - We randomised 40 elderly patients of mean age 74 years with displaced three- or
      four-part fractures of the humerus to either conservative treatment or tension
      band osteosynthesis. At one year and after three to five years, clinical follow
      up showed no functional differences between the two groups of patients, with
      optimal function achieved within one year. There were major complications only in
      the surgically-treated group. Radiological review showed that surgery had
      improved the position of the fractured humeral head, but this was not reflected
      in improved function. Semi-rigid fixation with tension-band wiring of displaced
      multifragment fractures of the proximal humerus in the elderly did not improve
      the functional outcome when compared with conservative treatment.

PMID- 9180320
TI  - Herbert screw fixation by limited access for acute fractures of the scaphoid.
AB  - We describe a semi-closed method of Herbert screw fixation for acute fractures of
      the scaphoid. All 40 patients treated achieved solid union with satisfactory
      wrist function. This technique gave a significantly shorter time to union and
      allowed an earlier return to manual labour compared with conservative treatment.
      There were no complications. Semi-closed insertion requires considerable skill,
      but produces consistently satisfactory results after minimal exposure of the
      scaphoid.

PMID- 9180321
TI  - The interosseous membrane in radio-ulnar dissociation.
AB  - In severe forearm injuries, the diagnosis of disruption of the interosseous
      membrane is frequently delayed and sometimes missed, giving difficulties in the
      salvage of forearm stability. We studied the structure and function of the
      interosseous membrane in 11 cadaver preparations, using mechanical and
      histological analysis. Seven of the specimens tested in uniaxial tension
      sustained a mid-substance tear of the central band of the membrane at a mean peak
      load of 1038 +/- 308 N. The axial stiffness was 190 +/- 44 N/mm with elongation
      to failure of 10.34 +/- 2.46 mm. These results provide criteria for the
      evaluation of reconstructive methods. A preliminary clinical investigation of the
      use of ultrasound suggests that this may be of value in the screening of patients
      with complex fractures of the forearm, and for investigating the natural history
      of tears of the interosseous membrane.

PMID- 9180322
TI  - Cancellous grafting and external fixation for unstable Colles' fractures.
AB  - We present a prospective study of the treatment of 32 unstable Colles' fractures
      by external fixation and cancellous grafting with minimal exposure. We inserted
      an external fixator between the radius and the second metacarpal, and maintained
      ligamentotaxis for five weeks. In 27 patients the result was good or excellent,
      but five fractures healed with malunion. All patients made a satisfactory
      functional recovery. At a mean follow-up of three years (1 to 5) after injury
      none had pain in the wrist and all were satisfied with the result. The average
      grip strength was 95% of normal. Seven patients had algodystrophy with mild
      impairment of finger movements in four. We conclude that the combination of
      cancellous grafting and external fixation is effective for the treatment of
      unstable Colles' fractures.

PMID- 9180323
TI  - External fixation and secondary intramedullary nailing of open tibial fractures.
      A randomised, prospective trial.
AB  - We performed a prospective, randomised trial in 39 patients with open tibial
      fractures treated initially by external fixation to compare cast immobilisation
      (group A) and intramedullary nailing (group B) as a sequential protocol planned
      from the onset of treatment. The results showed that group B achieved faster
      union (p < 0.05) than group A with less malunion or shortening and a greater
      range of movement. Patients treated by intramedullary nailing required fewer
      radiographs and outpatient visits (p = 0.0015) and had a more predictable and
      rapid return to full function. We feel that these severe fractures are better
      treated by delayed intramedullary nailing and that this has an acceptable rate of
      complications.

PMID- 9180324
TI  - Disruption of the pelvic ring during spontaneous childbirth. A case report.
AB  - A young woman sustained disruption of the anterior pelvic ring with bony avulsion
      of the symphysis pubis during a spontaneous delivery. Anterior external fixation
      allowed a full functional recovery.

PMID- 9180325
TI  - Fasciocutaneous blood supply in below-knee amputation.
AB  - Skin cover after below-knee amputation has been extensively discussed. We
      describe the flaps which are commonly used and discuss their vascular basis in
      the context of the current knowledge of the fasciocutaneous system. An
      understanding of this vascular system will enable surgeons to plan and shape
      flaps for surgical exposure and coverage.

PMID- 9180326
TI  - Fracture on removal of the ACE tibial nail.
AB  - We report four patients who sustained secondary fractures of the posterior wall
      of the tibial shaft during the removal of one pattern of intramedullary nail
      after fracture healing. The cause of this complication is discussed.

PMID- 9180327
TI  - Reconstruction of the lateral ligaments of the ankle using a regional periosteal
      flap.
AB  - We have treated 94 patients with chronic instability of the lateral side of the
      ankle by reconstruction of the ligaments with local periosteal tissue. We
      reviewed 90 cases after a mean follow-up of 2.8 years (2 to 9) using a
      questionnaire, clinical examination and radiography. The results on a 100-point
      ankle score indicated that 81% had a good or excellent result. The periosteal
      flap-replacement technique allows anatomical reconstruction and does not
      sacrifice other ligaments or tendons in the foot.

PMID- 9180328
TI  - Osteosynthesis without instrumentation for vertebral pseudarthrosis in the
      osteoporotic spine.
AB  - We have performed simple bone grafting in four elderly patients with pain due to
      unstable pseudarthroses in the osteoporotic spine after compression fracture. At
      operation, we observed abnormal movement of the affected vertebral body which was
      covered with a hypertrophic membrane; this seemed to inhibit the blood supply to
      the lesion. The thick membrane and avascular granulation in the false joint were
      excised and bone grafting carried out. Symptoms were dramatically improved
      immediately after operation and bony union was confirmed in the three surviving
      patients.

PMID- 9180329
TI  - A biomechanical evaluation of suture anchors in repair of the rotator cuff.
AB  - Repair of the rotator cuff requires secure reattachment, but large chronic
      defects cause osteoporosis of the greater tuberosity which may then have
      insufficient strength to allow proper fixation of the tendon. Recently, suture
      anchors have been introduced, but have not been fully evaluated. We have
      investigated the strength of suture-to-anchor attachment, and the use of suture
      anchors in repairs of the rotator cuff either to the greater tuberosity or the
      lateral cortex of the humerus. The second method gave a significant increase in
      the strength of the repair (p = 0.014). The repairs were loaded cyclically and
      failed at low loads by cutting into bone and tendon, casting doubt on the
      integrity of the repair in early mobilisation after surgery. Repairs with suture
      anchors did not perform better than those with conventional transosseous
      attachment.

PMID- 9180330
TI  - Can Trendelenburg's sign be positive if the hip is normal?
AB  - In 1895 Trendelenburg described his sign to determine the integrity of hip
      function. We found the sign to be positive in a patient whose hip was clinically
      and radiologically normal, and therefore investigated this in other patients. We
      confirmed that a medial shift of the mechanical axis of the leg below the hip may
      cause a positive Trendelenburg sign. This has not been previously described.

PMID- 9180331
TI  - Aseptic loosening of total hip replacement. Macrophage expression of inducible
      nitric oxide synthase and cyclo-oxygenase-2, together with peroxynitrite
      formation, as a possible mechanism for early prosthesis failure.
AB  - Aseptic loosening is a major cause of failure of total hip arthroplasty. The
      adverse tissue response to prosthetic wear particles, with activation of cytokine
      and prostanoid production, contributes to bone loss around the implants. We have
      investigated the possibility that inducible nitric oxide synthase (iNOS) and
      cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at
      the bone-implant interface, thereby contributing to the periprosthetic bone
      resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived
      oxidant associated with cellular injury, is generated in the membrane. Enzymatic
      activity of iNOS was measured using the arginine-citrulline assay technique and
      prostaglandin E2 (PGE2), as an indicator of COX-2 activity, was measured using an
      enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker
      of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative
      peroxidase immunocytochemistry while immunofluorescence methods were used for
      subsequent co-localisation studies with CD68+ macrophages. The presence of
      calcium-independent iNOS activity and PGE2 production was confirmed in the
      homogenised interface membrane. Immunocytochemistry showed that periprosthetic
      CD68+ wear-debris-laden macrophages were the most prominent cell type
      immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic
      inflammatory and resident cell types were also found to immunolocalise
      nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and
      cellular damage not only in NO-producing CD68+ macrophages, but also in their
      neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by
      CD68+ macrophages in the interface membrane and peroxynitrite-induced cellular
      damage is evident in such tissue. If high-output NO and peroxynitrite generation
      were to cause macrophage cell death, this would result in the release of
      phagocytosed wear debris into the extracellular matrix. A detrimental cycle of
      events would then be established with further phagocytosis by newly-recruited
      inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis.
      Since both NO and PGE2 have been implicated in the induction and maintenance of
      chronic inflammation with resulting loss of bone, and peroxynitrite in the
      pathogenesis of disease states, they may be central to the pathogenesis of
      aseptic loosening.

PMID- 9180332
TI  - The effects of particulate cobalt, chromium and cobalt-chromium alloy on human
      osteoblast-like cells in vitro.
AB  - Particulate wear debris can induce the release of bone-resorbing cytokines from
      cultured macrophages and fibroblasts in vitro, and these mediators are believed
      to be the cause of the periprosthetic bone resorption which leads to aseptic
      loosening in vivo. Much less is known about the effects of particulate debris on
      the growth and metabolism of osteoblastic cells. We exposed two human osteoblast
      like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt
      chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic
      to both cell lines and inhibited the production of type-I collagen, osteocalcin
      and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by
      both cell lines, producing no cytotoxicity and no inhibition of type-I collagen
      synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium
      inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium
      alloy inhibited osteocalcin expression. Our results clearly show that particulate
      metal debris can modulate the growth and metabolism of osteoblastic cells in
      vitro. Reduced osteoblastic activity at the bone-implant interface may be an
      important mechanism by which particulate wear debris influences the pathogenesis
      of aseptic loosening in vivo.

PMID- 9180333
TI  - Apoptosis and proliferation of growth plate chondrocytes in rabbits.
AB  - The growth plates of the femoral head of Japanese white rabbits aged 5, 10, 15
      and 20 weeks were stained for apoptotic and proliferating chondrocytes using the
      TUNEL and PCNA antibody staining techniques. Both TUNEL- and PCNA-positive
      chondrocytes were detected in all of the specimens. The positive ratios of both
      stainings were calculated for the whole plate and for the resting, proliferating
      and hypertrophic zones. The highest ratios in both stainings occurred in the
      hypertrophic zone in all age groups. With growth, the TUNEL-positive ratio
      increased whereas the proliferating ratio decreased. We suggest that the increase
      in chondrocytic death by apoptosis and the decrease in cell proliferation
      potential led to closure of the growth plate.

PMID- 9180334
TI  - Hydroxyapatite coating of threaded pins enhances fixation.
AB  - We measured the insertion and extraction torque forces in a randomised study of
      76 external fixation screws in 19 patients treated by hemicallotasis for
      osteoarthritis of the medial side of the knee. The patients were randomised to
      have either standard tapered screws (Orthofix 6/5 mm) or the same screws with
      hydroxyapatite (HA) coating. One patient had two standard and two HA-coated
      screws. All patients had an anterior external fixator (Orthofix T-garche), with
      two screws in the proximal tibial metaphysis parallel to and about 2 cm below the
      joint surface and two in the tibial diaphysis. The mean torque forces for
      insertion of the standard screws were 260 Ncm for the proximal to medial screw,
      208 for the proximal to lateral screw and 498 and 546 Ncm for the diaphyseal
      pins. The corresponding forces for the HA-coated pins were not significantly
      different. The torque forces for the extraction of the standard pins were 2 Ncm
      for the proximal pins, 277 and 249 Ncm for the distal pins and 482, 478, 585 and
      620 Ncm, respectively (p < 0.005) for the HA-coated pins. All 18 of the
      metaphyseal standard screws were loose at extraction (extraction force < 20 Ncm),
      but only one of the HA screws in the metaphysis was loose. In the diaphysis the
      standard screws lost about 40% of their fixation in contrast to the HA-coated
      screws which retained full fixation strength.

PMID- 9180335
TI  - Mechanosensitive afferent units in the lateral ligament of the ankle.
AB  - We have studied the mechanosensitive afferent units in the lateral ligament of
      the ankle of the cat, with reference to the causes of lateral instability after
      injury, using electrophysiological recording from the lumbar dorsal rootlets. We
      identified 30 mechanosensitive units in the lateral ligament; 28 (93%) were
      located near the attachment to the fibula and calcaneus, which included both low
      threshold group-II units and low- and high-threshold group-III units. Our results
      indicate that there are both proprioceptors and nociceptors in the lateral
      ligament of the cat ankle, and confirm that afferent fibres from the lateral
      ligament may contribute to the stability of the joint by regulation of position
      and movement.

PMID- 9180336
TI  - Mechanoreceptors in the palmar wrist ligaments.
AB  - Three palmar wrist ligaments from fresh human cadavers were dissected from the
      proximal to the distal insertions and stained to identify the mechanoreceptors.
      Golgi organs, Pacinian corpuscles, Ruffini endings and free nerve endings were
      present in all three ligaments. In the radial collateral and radiolunate
      ligaments they were found in increased density towards the proximal and distal
      insertions. A more uniform distribution was found in the radioscaphocapitate
      ligament which has attachments to three bones. The palmar wrist ligaments may
      have a significant sensory role in maintaining the stability of the wrist and in
      controlling its movement. Although technically difficult, the surgical repair of
      traumatic wrist defects should attempt to preserve the innervation of the
      ligaments, shown to be mainly near bony attachments. This may allow improvement
      in postoperative outcomes by preserving some proprioception. In some painful post
      traumatic or degenerative conditions, however, denervation may be advantageous.

PMID- 9180337
TI  - Massive prostheses for malignant bone tumours of the limbs.

PMID- 9180338
TI  - Graded compression stockings for the prevention of deep-vein thrombosis.

PMID- 9180340
TI  - Non-cemented replacement of the trapeziometacarpal joint.

PMID- 9180341
TI  - Simple bone cysts treated by percutaneous autologous marrow grafting.

PMID- 9180342
TI  - Care of the polytraumatised patient.

PMID- 9180343
TI  - Rotational acetabular osteotomy for severe dysplasia of the hip.

PMID- 9180345
TI  - Effect of lithium on superoxide production and intracellular free calcium
      mobilization in elastin peptide (kappa-elastin) and FMLP stimulated human PMNS.
      Effect of age.
AB  - The effect of lithium pretreatment on superoxide anion production and
      intracellular free calcium levels was investigated in polymorphonuclear
      leukocytes (PMN) from middle-aged and old individuals after stimulation by
      elastin peptides or FMLP. K-elastin (KE) significantly stimulated the production
      of superoxide anion by PMNs from middle-aged subjects, while this stimulation
      decreased with age and was absent in PMNs of elderly arteriosclerotic patients.
      Li pretreatment slightly increased this stimulating effect of KE in PMNs from
      middle-aged subjects and elderly arteriosclerotic patients, while slightly
      decreased in healthy elderly subjects. Moreover, Li was able to increase
      superoxide anion production even in the absence of KE, but this effect decreased
      also in PMNs of healthy and arteriosclerotic elderly patients. FMLP significantly
      increased superoxide anion production in all age-groups, but this effect was
      further amplified by Li only in PMNs of middle-aged subjects. In aged individuals
      Li pretreatment slightly decreased the effect of FMLP and had no effect in
      arteriosclerotic patients. Ca-mobilization induced by KE was inhibited by Li
      pretreatement in each age group. This inhibition by Li was much weaker in FMLP
      stimulated PMNs. Li pretreatment did however modify the shape of the Ca-transient
      curves in FMLP stimulated leukocytes suggesting a qualitative modification of ion
      channel regulation. No such shape change of Ca-transient curves was observed
      after KE stimulation of Li pretreated PMNs. It appears that the regulation of
      these two receptors is differently affected by Li treatment.

PMID- 9180344
TI  - Modulation of apomorphine-induced rotations in unilaterally 6-hydroxydopamine
      lesioned rats by cholinergic agonists and antagonists.
AB  - In the present study, we examined the effects of the agonists and antagonists of
      cholinergic receptors on central dopaminergic function using the 6
      hydroxydopamine model of dopamine receptor supersensitivity. Unilateral lesioning
      of the substantia nigra with 6-hydroxydopamine was carried out in Wistar rats.
      Two weeks after surgery, the rats were tested for the presence of dopaminergic
      supersensitivity by their response to the dopamine receptor agonist, apomorphine.
      Apomorphine-induced rotations were significantly reinforced by the muscarinic
      receptor antagonist, atropine. In contrast to atropine, the muscarinic receptor
      agonist oxotremorine attenuated apomorphine's effects. Acute treatment of
      nicotine significantly reduced apomorphine-induced rotations. However, when
      increasing doses of nicotine were given for nine days, the rotations of the
      nicotine-dependent rats were significantly enhanced. So the fact that both
      muscarinic and nicotinic cholinergic activity could modulate apomorphine-induced
      rotations was readily apparent in these experiments.

PMID- 9180346
TI  - Antinociceptive effect of buprenorphine in mu1-opioid receptor deficient CXBK
      mice.
AB  - The antinociceptive effect of buprenorphine was examined in mu1-opioid receptor
      deficient CXBK mice. I.p. administration of buprenorphine at a dose of 3 mg/kg
      produced marked antinociception in the tail-flick test in C57BL/6 mice, a
      progenitor strain of CXBK mice. The antinociceptive effect of buprenorphine in
      C57BL/6 mice was antagonized by pretreatment with either beta-funaltrexamine
      (beta-FNA), a mu-opioid receptor antagonist, or naloxonazine (NXZ), a selective
      mu1-opioid receptor antagonist. The antinociceptive effect of buprenorphine (3
      mg/kg, i.p.) in CXBK mice was significantly less than that in C57BL/6 mice.
      Neither beta-FNA nor NXZ reduced the antinociceptive effect of buprenorphine in
      CXBK mice. There was no significant difference between the buprenorphine-induced
      antinociceptive effect in CXBK mice and NXZ-treated C57BL/6 mice. Furthermore,
      neither naltrindole, a selective delta-opioid receptor antagonist, nor
      norbinaltorphimine, a selective kappa-opioid receptor antagonist, had a
      significant effect on the antinociceptive effects of buprenorphine in both CXBK
      and C57BL/6 mice. These results support our previous hypothesis that mu1- rather
      than mu2-, delta- or kappa-opioid receptors are involved in the antinociceptive
      effects of buprenorphine.

PMID- 9180347
TI  - Effect of valproate on the metabolism of the central nervous system.
AB  - The effects of valproate on brain energy and lipid metabolism is reviewed.
      Increasing evidence suggests that valproate uses the monocarboxylic acid carrier
      in order to cross the blood brain barrier (BBB) and the neural cell plasma
      membranes. The uptake of valproate into the brain through this mechanism would
      compete with the uptake of energy precursors, such as the monocarboxylic acids 3
      hydroxybutyrate, lactate or pyruvate and with some amino acids, but not with
      glucose. This could impair brain fuel utilization, specially during the neonatal
      period or childhood, when lactate or 3-hydroxybutyrate furnishes alternative
      substrates to glucose for the brain. It is concluded that valproate interference
      with energy metabolism may have implications for the therapeutic action of the
      drug, stressing the possibility that valproate-mediated alterations in brain
      lipid synthesis may contribute to the pharmacological action of the drug.

PMID- 9180348
TI  - Expression and inducibility of UDP-glucuronosyltransferases 1-naphthol in human
      cultured hepatocytes and hepatocarcinoma cell lines.
AB  - The UDP-glucuronosyltransferase (UGTs) isoforms involved in the conjugation of 1
      naphthol were characterized in human cultured hepatocytes and in two human
      hepatocarcinoma cell lines, KYN-2 and Mz-Hep-1 in terms of expression, kinetics
      and induction by drugs. Their properties were compared to those of UGT1*6 stably
      expressed in the V79 cell line (V79UGT1*6), which glucuronidates 1-naphthol
      preferentially. The determination of kinetic constants for glucuronidation of 1
      naphthol revealed a two-site model in human hepatocytes, but a one-site model in
      the two hepatocarcinoma cell lines. Southern blot analysis of RT-PCR products,
      showed that the UGT1*6 mRNA was expressed in KYN-2, but not in Mz-Hep-1 cells.
      However, a mRNA encoding a UGT different from UGT1*6 was expressed in Mz-Hep-1
      cells. The two inducers, beta-naphthoflavone and rifampicin exerted a
      differential effect, depending on the cell lines considered. Altogether, the
      results suggest that, in hepatocytes, two UGT isoforms, which glucuronidate 1
      naphthol are expressed and are differentialy regulated by inducers. Both KYN-2
      and Mz-Hep-1 cells express one of the two different UGT isoforms found in
      hepatocytes. The UGT isoform present in KYN-2 cells corresponds to UGT1*6,
      whereas in Mz-Hep-1 cells the UGT isoform present was different from UGT1*6 and
      UGT1*7.

PMID- 9180349
TI  - Involvement of cytochrome P450 3A4 in N-dealkylation of buprenorphine in human
      liver microsomes.
AB  - Buprenorphine is a long acting analgesic of the opiate family. Recently, it has
      been proposed for the opioid dependency treatment at a large scale. The drug is
      extensively metabolized by the hepatic cytochrome P450 in man, yielding a N
      dealkylated metabolite, norbuprenorphine. The specific forms of P450 involved in
      this oxidative N-demethylation were examined in a panel of 18 human liver
      microsomal preparations previously characterized with respect to their P450
      contents. Buprenorphine was N-dealkylated with an apparent Km of 89 +/- 45 microM
      (n = 3). The metabolic rates were 3.46 +/- 0.43 nmol/(min x mg of protein). This
      metabolic pathway was strongly correlated with 6 catalytic activities specific to
      P450 3A4 and with the immunodetectable P450 3A content of liver microsomal
      samples (r = 0.87). Buprenorphine metabolism was 62-71% inhibited by three
      mechanism-based inhibitors (TAO, erythralosamine, gestodene), by nifedipine as
      competitive inhibitor (Ki = 129 microM) and by ketoconazole 0.6 microM (25%
      residual activity), all these inhibitors specific to P450 3A. Among 10
      heterologously expressed P450s tested, only P450 3A4 was able to dealkylate
      buprenorphine with a turnover number of 9.6 min(-1). Morever, this catalytic
      activity was inhibited up to 80% (vs control) by anti-rat P450 3A antibody. Taken
      together, all these data demonstrate that P450 3A4 is the major enzyme involved
      in hepatic buprenorphine N-dealkylation.

PMID- 9180350
TI  - 5-hydroxytryptamine decreases somatostatin receptors and somatostatin-responsive
      adenylyl cyclase in rat pancreatic acinar membranes.
AB  - Pretreatment of pancreatic acini with 5-hydroxytryptamine (5-HT) reduced the
      binding of the labeled somatostatin (SS) analogue 125I-Tyr3-SMS to pancreatic
      acinar membranes. This effect was dependent of the dose of 5-HT used and length
      of pretreatment. This inhibitory effect of 5-HT was abolished when pancreatic
      acini were pretreated with 5-HT in the presence of the 5-HT1p receptor-antagonist
      5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP). Pretreatment of
      pancreatic acini with 5-HT reduced the inhibition by the stable SS analogue SMS
      201-995 of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity in
      pancreatic acinar membranes. There was no statistical difference established
      between IC50 values for the stable GTP analogue 5'-guanylylimidodiphosphate
      (Gpp(NH)p) which inhibits ligand binding to SMS receptors in controls and in 5-HT
      treated pancreatic cells, respectively. In addition, no significant differences
      were seen in the level of Gi proteins in the control and 5-HT treated pancreatic
      acini. These data suggest that the decrease of the number of 125I-Tyr3-SMS
      receptors, would explain the decreased sensitivity of AC to SMS 201-995 in
      membranes from 5-HT-pretreated acini.

PMID- 9180351
TI  - Calcium dynamics in cultured heart cells exposed to defibrillator-type electric
      shocks.
AB  - Spatial and temporal changes in intracellular calcium ion concentration and
      transmembrane voltage were recorded optically from single-isolated cultured chick
      embryo heart cells exposed to high-voltage, defibrillator-type shocks.
      Fluorescence changes were measured during 5 msec electric shocks of field
      strengths up to 56 volts/cm in single myocytes stained with a Ca(++)-sensitive or
      voltage-sensitive dye. Shocks caused a reversible period of depolarization,
      elevated cytosolic Ca++, and refractoriness. Intracellular Ca++ elevation had two
      temporal phases: first, a Ca++ spike with morphology independent of shock
      intensity; and second, a prolonged Ca++ elevation with a shock-intensity
      dependent magnitude and duration, and with greatest Ca++ elevation at the poles
      of the cell adjacent to the electrodes. The prolonged elevation (second phase)
      was initiated earlier at the anode-facing pole of the cell than at the cathode
      facing pole. These results suggest that postshock Ca++ entry consists of two
      parts: early normal entry through excitation channels plus a prolonged elevation
      which may be related to cellular damage.

PMID- 9180352
TI  - Cardiovascular effects of the fungal extract of basidiomycetes sp. YL8006.
AB  - Many fungal products are known to possess biological activity towards the
      mammalian tissues. We studied vasodilating activity in the crude ethanol extract
      of the dried mycelia of Basidiomycetes sp. YL8006, cultured by submerged
      fermentation with a complex medium. The activity was assayed using the isolated
      perfused rat heart in the working mode. Immediately following injection of the
      extract into the perfusion system, a 20-25% increase in coronary flow was
      observed (p<0.001 vs. solvent vehicle control). There was a concurrent decrease
      in diastolic pressure and coronary vascular resistance. Aortic flow, systolic
      pressure, and cardiac output declined slightly over time after treatment. No
      significant changes in heart rate, efficiency, and oxygen consumption were
      observed. Solvent vehicle did not cause any changes in hemodynamic performance.

PMID- 9180353
TI  - Molecular rigidity and potency of bispyridinium type allosteric modulators at
      muscarinic M2-receptors.
AB  - Several bispyridinium compounds have been shown to be potent allosteric
      modulators of ligand binding to muscarinic M2-receptors. ,,Uno compounds" are
      benzyl derivatives of the bispyridinium "TMB4" (trimethylene-bis-[4-hydroxy
      iminomethyl-pyridinium]). To gain more insight into structure activity
      relationships, eleven derivatives with varying structure of the oxime-linked
      aromatic substituent were tested for their ability to inhibit the equilibrium
      binding of [3H]N-methylscopolamine ([3H]NMS) in guinea pig cardiac membranes and
      to retard [3H]NMS-dissociation allosterically. At a concentration of 3 microM,
      all compounds reduced [3H]NMS-binding to about 40 % of the control level,
      indicating a similar potency to inhibit the association of [3H]NMS. Allosteric
      retardation of [3H]NMS-dissociation required higher concentrations. Comparing the
      effects of the compounds at 30 and 300 microM, respectively, revealed
      considerable differences in potency. Therefore, the concentration-dependency of
      the delay of [3H]NMS-dissociation was determined for selected compounds. The
      results indicate that introduction of a benzyl-moiety into TMB4 leads to a 20
      fold increase in allosteric potency. A further increment by a factor of 10 is
      obtained with the 2,6-dichlorobenzyl-substitution and with the naphthyl
      derivative. The other compounds were less potent. An inverse correlation was
      found between the rotational freedom of the aromatic substituent and the
      allosteric potency. In conclusion, the aromatic moiety of non-symmetric
      bispyridinium-type modulators does not seem to be part of the pharmacophore
      involved in the inhibitory effect on the association of [3H]NMS. In contrast, a
      rigid aromatic lateral moiety appears to be essential for the interaction with
      the recognition site mediating the allosteric delay of [3H]NMS dissociation from
      muscarinic M2-receptors.

PMID- 9180354
TI  - Dopamine and the regulation of cell proliferation in gerbil (Meriones
      unguiculatus) pyloric mucosa.
AB  - The epithelium of the digestive system mucosa consists of a highly dynamic cell
      population. The conditions under which mitotic activity in the gastrointestinal
      epithelium is regulated is as yet poorly understood. Nevertheless, it is assumed
      that some biogenic amines might be involved. Having demonstrated that
      dopaminergic cells occur in the stomach of gerbils (Meriones unguiculatus), in
      the present study we examined the influence of dopamine antagonist haloperidol on
      the proliferation of epithelial cells in the mucosa of the stomach. Proliferating
      cells were detected immunocytochemically and quantified after in-vivo labeling
      with 5-bromo-2'-desoxyuridine in both haloperidol- and saline-treated animals.
      The results show that acute doses of haloperidol significantly increases the
      proliferation rate in the pyloric mucosa, suggesting that dopamine plays a
      probable modulatory role in the regulation of mitotic activity. These findings
      are discussed with regard to the role of paraneurons in regulating epithelial
      mitosis.

PMID- 9180355
TI  - Conjugation-deconjugation cycling of diflunisal via beta-glucuronidase catalyzed
      hydrolysis of its acyl glucuronide in the rat.
AB  - The role of beta-glucuronidase catalyzed hydrolysis of glucuronides on the in
      vivo disposition kinetics of xenobiotics was studied in the rat. The metabolic
      disposition kinetics of diflunisal, a compound undergoing transformation to an
      acyl and phenyl glucuronide, were studied in rats under control conditions and
      following administration of D-glucaro-1,4-lactone, a potent and specific beta
      glucuronidase inhibitor. D-glucaro-1,4-lactone treatment resulted in a
      significant decrease in beta-glucuronidase activity in plasma, urine, and hepatic
      microsomes. Total (i.e. urinary and biliary) recovery of the acyl glucuronide
      following i.v. injection of diflunisal (10 mg/kg) was significantly higher in D
      glucaro-1,4-lactone treated rats (41 +/- 3%, n=6) compared to control rats (29 +/
      2%, n=6) whereas for diflunisal phenyl glucuronide this total recovery was very
      similar in both groups of rats (16.0 +/- 1.0% vs. 18.0 +/- 0.2%, n=6,
      respectively). The partial clearance of diflunisal associated with the formation
      of the acyl glucuronide was significantly higher in D-glucaro-1,4-lactone treated
      rats (0.413 +/- 0.024 ml/min/kg) compared to control animals (0.269 +/- 0.042
      ml/min/kg). The partial clearance related to the formation of the phenyl
      glucuronide, on the contrary, was not significantly affected by D-glucaro-1,4
      lactone treatment. These results shows that the in vivo glucuronidation of
      diflunisal to the acyl glucuronide, unlike diflunisal glucuronidation to the
      phenyl glucuronide, is subject to a futile conjugation-deconjugation cycle. Such
      futile cycling may have significant therapeutic and toxic implications.

PMID- 9180356
TI  - Effects of the circadian rhythm of corticosteroids on leukocyte-endothelium
      interactions in the AM and PM.
AB  - Circadian rhythms are responsible for a number of key cycles within the body. In
      vivo microscopy was used to investigate the hypothesis that the circadian rhythm
      of corticosterone in rats produces different leukocyte-endothelium interactions
      throughout the day. The data indicate that corticosterone levels range from 12
      ng/ml in the AM to 260 ng/ml in the PM. In contrast, the number of circulating
      polymorphonuclear leukocytes (PMNs) yields peak values in the AM (630
      PMNs/microl) and trough values in the PM (262 PMNs/microl). During surgical
      stress there is a significant increase in the number of circulating PMNs in the
      PM but little change in the AM. Furthermore, there is significantly greater
      leukocyte-endothelium adhesion in the PM (5.2 cells/100 microm) than in the AM
      (2.9 cells/100 microm). Addition of the chemoattractant FMLP increased adhesion
      125% in the AM but only 62% in PM. Both exogenous glucocorticoid supplementation
      for 2 weeks and bilateral adrenalectomy abolished the circadian rhythms of
      circulating PMNs, the number of sticking white blood cells and the initial stages
      of an acute inflammatory response. These findings suggest that the circadian
      rhythm of corticosterone alters leukocyte-endothelium interactions throughout the
      day.

PMID- 9180357
TI  - Costimulation, tolerance and ignorance of cytolytic T lymphocytes in immune
      responses to tumor antigens.
AB  - Despite the fact that many tumors express MHC class I molecules presenting
      "foreign" peptide antigens, a vigorous tumor-destructing immune response is
      seldom detected. A possible explanation is that tumors cannot provide adequate
      costimulatory signals as provided by professional antigen presenting cells. CD28,
      upon interacting with B7, triggers costimulatory signals critical for the T-cell
      response. Transfection of tumor cells with B7 augments the immunogenicity of the
      tumor so that an anti-tumor immune response can be amplified. When B7-CD28
      costimulation is provided CTL specific for otherwise silent epitopes can be
      activated. Therefore, unresponsiveness of T cells to many tumor antigens should
      be considered as ignorance rather than tolerance. Immunological ignorance may
      thus contribute to the failure of the immune system to respond against the tumor
      antigens.

PMID- 9180358
TI  - Dual coupling and down regulation of human FSH receptor in CHO cells.
AB  - The FSH receptor is a member of the family of G protein-coupled receptors that
      activate adenylyl cyclase. The binding of agonist to cell surface receptors leads
      to a reduction in the intensity of the response to continuous stimulation, a
      process that is usually referred to as desensitization. Although the exact
      mechanism is not fully understood, the molecular cloning of the FSH receptor has
      made it possible to study desensitization in transfected cell lines. In this
      experiment FSH-induced desensitization was studied using Chinese hamster ovary
      cells expressing a functional human FSH receptor (CHO-FSHR cells). Stimulation of
      the CHO-FSHR cells with 10 ng/ml human FSH resulted in a decreased sensitivity to
      a second FSH stimulation. This decrease in FSH-induced cAMP production was
      observed within 2 h, and exposure of cells to FSH for 20 h led to a 70-80 %
      inhibition of cAMP formation. Moreover, the desensitization effect observed in
      CHO cells was mimicked by forskolin and, therefore, was mediated by cAMP.
      Incubation of cells with 125I-FSH showed an efficient internalization of the
      ligand in the CHO-FSHR cells. The CHO-FSHR cells rapidly internalized
      approximately 30% of the receptor-associated 125I-FSH by 2 h and 50% by 4 h. The
      responsiveness of individual CHO-FSHR cells to FSH was studied and administration
      of human FSH (30 ng/ml) induced a rapid rise in cytosolic calcium, reaching a
      peak at 6 sec. The data that human FSH can increase intracellular calcium in
      cells transfected with the FSH receptor cDNA reveal the possibility for the human
      FSH receptor to couple to both adenylyl cyclase and phospholipase C cascades.

PMID- 9180359
TI  - Potentiation of histamine-induced catecholamine secretion by ouabain in cultured
      bovine adrenal chromaffin cells is dependent on calcium and sodium influx.
AB  - The effects of histamine on catecholamine secretion from cultured bovine adrenal
      chromaffin cells were studied in the presence of ouabain, an inhibitor of Na+-K+
      ATPase. The purpose of this study was to determine whether Na+, as well as Ca2+,
      was involved in histamine receptor-mediated catecholamine secretion. Histamine
      (10(-8)-10(-5) M)-induced catecholamine secretion was markedly potentiated by
      addition of ouabain (10(-5) M) and was inhibited by a histamine-H1 receptor
      antagonist or incubation in a Ca2+-free medium. Histamine-induced 45Ca2+ influx
      was also potentiated by addition of ouabain. Ouabain alone or in the presence of
      histamine increased 22Na+ influx into the cells. In an additional set of
      experiments, cells were preincubated in the presence or absence of Na+ for 30 min
      (+/- histamine and ouabain), washed and then catecholamine secretion was measured
      following exposure to 2.2 mM Ca2+ for 15 min. Preincubation with histamine alone
      with or without Na+ had no effect of Ca2+-induced secretion of catecholamine.
      Preincubation with ouabain alone or with ouabain plus histamine produced a slight
      stimulation of catecholamine secretion in Na+-free medium and a large stimulation
      in Na+-containing medium. These results suggested that stimulation of the
      histamine-H1 receptor and inhibition of the Na+ pump both increase intracellular
      Na+ levels, resulting in increases in Ca2+ influx and catecholamine secretion.

PMID- 9180360
TI  - Induction of antioxidant enzymes by dexamethasone in the adult rat lung.
AB  - Catalase, glutathione peroxidase and superoxide dismutase enzymes were determined
      after administering dexamethasone. Catalase increased its activity over six times
      (0.388 U/mg DNA) the normal rate, while glutathione peroxidase caused 3 times an
      increase one hour after dexamethasone injection. Superoxide dismutase increased
      gradually during the 3 hour treatment. The antioxidant enzyme activities
      decreased to basal values in the presence of protein synthesis (Cycloheximide)
      and RNA synthesis (Actinomycin D) inhibitors. The current report demonstrates
      that the increase of antioxidant enzymes is due to an enzymatic induction
      mechanism, and not due to an activation process.

PMID- 9180361
TI  - Cloning, functional expression and tissue distribution of rabbit alpha1a
      adrenoceptor.
AB  - A cDNA clone, which has an open reading frame of 1398 nucleotides encoding a 466
      amino-acid peptide, has been isolated from rabbit liver cDNA library. Compared
      with the peptide sequence, it shows high homology to alpha1a adrenoceptors of
      human, bovine and rat. We expressed this clone in COS-7 and investigated the
      pharmacological properties, revealing similarity to those of human alpha1a
      adrenoceptors. Competitive RT/PCR has detected the mRNA in variety of rabbit
      tissues, especially abundantly in liver, vas deferens, brain, and aorta, but not
      in heart.

PMID- 9180362
TI  - Marijuana intoxication and brain activation in marijuana smokers.
AB  - OBJECTIVE AND METHOD: The acute effects of delta9 tetrahydrocannabinol (THC) on
      cerebral blood flow (CBF) were studied in human subjects. Regional CBF was
      measured with 15O-water and Positron Emission Tomography (PET) in 32 volunteers
      with a history of exposure to marijuana. Scans were performed before and after
      intravenous (I.V.) infusion of either of two doses of THC or a placebo, given
      under double blind conditions. RESULTS: THC but not placebo increased CBF
      especially in the frontal regions bilaterally, insula and cingulate gyrus and sub
      cortical regions with somewhat greater effects in the right hemisphere. While
      most regions showed significant change at 60 minutes for the lower dose group,
      the higher dose group had significant change at 30 and 60 minutes. There was a
      highly significant change in the anterior/posterior ratio for the two THC groups
      reflecting minimal change in occipital flow but significant increases in frontal
      flow. Self ratings of THC intoxication showed significant effects, and regression
      analysis indicated it correlated most markedly with the right frontal region.
      CONCLUSION: Behavioral manifestations of marijuana intoxication may be associated
      with increased functional activity of the brain especially the frontal cortex,
      insula and cingulate gyrus.

PMID- 9180363
TI  - Chronopharmacological study of KE-SI-TO in mice.
AB  - Influence of dosing time on pharmacological effects and toxicity of KE-SI-TO
      (KST), analgesic and antipyretic drug, was investigated in ICR male mice under LD
      (12:12) cycle. Significant circadian rhythms were demonstrated for analgesic and
      hypothermal effects of KST (1 g/kg, i.p.) with higher values in the dark and
      lower ones in the light (p<0.01, respectively). The rhythmic patterns of KST
      induced analgesia and hypothermia resembled overall the rhythms occuring in the
      nondrugged state. Injection of KST resulted in a parallel increasing in latency
      to hot plate and a parallel decreasing in rectal temperature. KST (6 g/kg, i.p.)
      induced toxicity also showed a significant circadian rhythm with the highest
      mortality at 1700 and the lowest one at 0500 (p<0.05). The principles and
      concepts of biological rhythm should be included in the consideration of the
      actions of KST.

PMID- 9180364
TI  - Kinetics of PAF transfer, distribution and metabolism in human blood in vitro.
AB  - The transfer kinetics of PAF (0.1-100 nM), deposited as a thin film on a plastic
      surface, to human blood were studied under conditions of physiological
      significance. Almost all (83-87%) available PAF was solubilized in two waves.
      Initially, 40-50% of the available PAF was transferred to blood very fast in less
      than 15 seconds while the rest, 30-45%, obeyed first order kinetics, 0.0226 <
      k(app) < 0.0319 sec(-1). Blood cells following a parallel to whole blood binding
      time course bound 20-25% of the solubilized PAF. Dilution of blood up to 1:9 with
      0.15M NaCl did not affect PAF transfer parameters favouring an aqueous phase
      diffusion mechanism. Blood-bound PAF was allocated mainly to plasma, 67 +/- 4%,
      erythrocytes, 18 +/- 1% and platelets, 5 +/- 1%. These data indicated the role of
      the high affinity binding sites in human platelets versus the low affinity
      binding by erythrocytes, although the latter, due to their number, dominated cell
      bound PAF. Even at 100 nM there were no saturation signs for the transfer of PAF
      to blood or blood cells. PAF hydrolysis did not affect its binding to the blood
      elements. Given infinite time only 62 +/- 1% of the blood bound PAF would be
      metabolised by the rather slow acting, 11.5 > t(1/2) > 6.5 min, PAF
      acetylhydrolase.

PMID- 9180365
TI  - The effects of brain and C-type natriuretic peptides on corticotropin-releasing
      factor in brain of rats.
AB  - The central corticotropin-releasing factor (CRF)-ergic system plays a critical
      role in anxiety and other behavioral stress responses. It has been shown that
      atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides exert anxiolytic
      like effects in behavioral studies. Our previous findings demonstrated that
      various doses of centrally administered ANP selectively altered the CRF content
      in different brain areas. In the present study, CRF immunoreactivity was
      determined in hypothalamic and extrahypothalamic brain regions after central
      injection of BNP or CNP in rats. A high dose (400 ng) of BNP significantly
      increased the CRF-like immunoreactivity (CRF-LI) in the hypothalamus and
      amygdala, while only a tendency towards an increase was found in the hippocampus.
      In the hypothalamus, the CRF-LI decreased after a high dose (400 ng) of CNP. The
      CRF-LI increased in the basal forebrain after a low dose (100 ng) of CNP. These
      results suggest that CRF may be involved in the mediation of some neuroendocrine
      and behavioral responses to BNP and CNP.

PMID- 9180366
TI  - Glycation of collagen in hypertriglyceridemic rats.
AB  - Nonenzymatic collagen glycation and modification with lipid derived metabolites
      was studied in rat skin and tail tendon collagen of control and
      hypertriglyceridemic (HTG) rats. Age-dependent changes typical for lipid and
      sugar derived adducts were evaluated by measuring fluorescence of these collagens
      at wavelengths typical for sugar (335/385 and 370/440 nm) and lipid derived
      adducts (356/460 and 390/460 nm). In addition pentosidine assay (corresponding to
      the fluorescence parameters 335/385 nm) was performed as well. It was found that
      pentosidine concentration as well as fluorescence intensities in skin collagen
      was the same for control and HTG rats and significantly increased with age. On
      the other hand, no significant age-dependent changes in fluorescence intensities
      were observed in tail tendon collagen. Pentosidine concentration in tail tendon
      collagen was much lower than that in skin and it was decreased in young HTG rats
      compared to control ones. It increased with age, more distinctly in HTG rats than
      in their control counterparts, in such a way that at the age of 19 months the
      pentosidine levels were undistinguishible in both rat strains. Possible
      mechanisms underlying these results are discussed.

PMID- 9180367
TI  - Mercury dynamics in hair of rats exposed to methylmercury by synchrotron
      radiation X-ray fluorescence imaging.
AB  - Two-dimensional distribution of mercury (Hg) in hair samples of rats exposed to
      methylmercury (MeHg) was analyzed by synchrotron radiation X-ray fluorescence (SR
      XRF) imaging. Experiments with endogenous- and exogenous-model for MeHg exposure
      revealed that the metal level was obviously higher in the hair cortex after the
      former exposure whereas a dominant site that Hg distributed after the latter
      exposure was the cuticle. The method also provided us the Hg profile along the
      hair length with a single hair obtained by the endogenous model. Thus application
      of SR-XRF analysis to hair sample would facilitate biological monitoring to not
      only distinct Hg exposure but also determine its dynamics with only the specimen.

PMID- 9180368
TI  - Association between angiotensin converting enzyme gene polymorphism and clinical
      features in autosomal dominant polycystic kidney disease.
AB  - We investigated the association between angiotensin converting enzyme (ACE) gene
      polymorphism and clinical manifestations in 47 patients with autosomal dominant
      polycystic kidney disease (ADPKD). One-hundred, age- and sex-matched subjects
      with non-ADPKD served as the controls. ACE gene polymorphism was analysed using a
      GeneAnp kit. Renal size was determined by abdominal CT scan, by adding the
      longitudinal axis of each kidney. Incidence of extrarenal complication was also
      examined. Out of 47 patients, 24 patients (51%) were II, 18 (38%) ID and 5 (11%)
      DD type. The frequencies of the I and D alleles as well as the distributions of
      ACE genotypes in ADPKD did not differ from those in controls. The number of
      patients undertaking renal replacement therapy was 11 in II (46%), 6 (33%) in ID
      and 2 (40%) in DD genotype, respectively, that was not significantly different
      among the groups. The mean age of the initiation of renal replacement therapy did
      not vary among the three genotypes. The slopes of 1/serum creatinine did not
      differ between II and ID genotypes, whose initial serum creatinine levels ranged
      from 1.5 to 2.5 mg/dl. Renal size, blood pressure, and extrarenal complications
      including liver cysts and cardiac valvular disease were unrelated to the ACE
      genotypes. The present data suggested the irrelevance of ACE gene polymorphism in
      clinical manifestations in patients with ADPKD.

PMID- 9180369
TI  - Demonstration and purification of a myristoyl-CoA binding protein from bovine
      cardiac muscle.
AB  - Protein myristoylation refers to the co-translational addition of myristoyl group
      to an amino-terminal glycine residue of a protein by the enzyme myristoyl
      CoA:protein N-myristoyltransferase (NMT). The myristoylation reaction depends on
      the availability of the cellular pools of coenzyme A and myristate and their
      subsequent formation of myristoyl-CoA, the substrate of NMT. In the present study
      a myristoyl-CoA binding protein (MCBP) was purified using various column
      chromatographies: hydroxylapatite, DEAE Sepharose CL-6B and Sephacryl S-300 gel
      filtration. The purified protein exhibited an apparent molecular mass of 50 kDa
      on SDS-polyacrylamide gel electrophoresis. Incubation of protein with [1
      (14)C]myristoyl-CoA followed by denaturing gel electrophoresis, fluorography and
      treatment with hydroxylamine yielded results that are highly suggestive of a
      covalent ester-linked acyl-protein complex. This complex formation was not
      observed in the crude cytosolic fractions. The addition of cytosolic fraction to
      a progressing acyl-protein complex, resulted in deacylation suggesting a role for
      thioesterase or/proteinases in the regulation of the acylation reaction in bovine
      cardiac muscle. The acyl-protein complex formation was not inhibited by NIP71, a
      71 kDa NMT inhibitory protein from bovine brain.

PMID- 9180370
TI  - Aggravation of DMCM-induced seizure by nitric oxide synthase inhibitors in mice.
AB  - The present study investigated the effects of nitric oxide synthase (NOS)
      inhibitors on the seizure threshold of DMCM in mice. The seizure threshold of
      DMCM was evaluated using an intravenous infusion technique. The threshold of DMCM
      was significantly decreased by pretreatment with N-nitro-L-arginine (NOARG; 8
      mg/kg) and N-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg), but not with D
      NAME. Furthermore, these NOS inhibitors also decreased the threshold for
      pentylenetetrazole-induced seizure. However, the threshold for caffeine-induced
      seizure was not affected by NOARG. These results suggest that the endogenous NO
      system may play an important role in the expression of seizure by GABA(A)
      receptor inhibitory agents (DMCM and PTZ).

PMID- 9180371
TI  - A comparison of human immunodeficiency virus type 1 inhibition by partially
      purified aqueous extracts of Chinese medicinal herbs.
AB  - A multiple screening approach to detect compounds inhibitory to various aspects
      of the human immunodeficiency virus type 1 (HIV-1) life-cycle has been applied to
      aqueous extracts of 19 herbs traditionally used in Chinese medicine as anti-viral
      agents. The extracts were tested for their ability to inhibit HIV-1 in a series
      of in vitro assays. The extracts were tested for inhibition of the interaction
      between HIV-1 gp120 and immobilized CD4 receptor, inhibition of recombinant HIV-1
      reverse transcriptase and for inhibition of three glycohydrolase enzymes that
      contribute to viral protein glycosylation. Six of the herb extracts (30%) were
      potent inhibitors of the interaction between HIV-1 gp120 and the CD4 receptor
      (ID50 5.6 - 79.4 microg/ml), two extracts (10%) contained potent reverse
      transcriptase inhibitors (ID50 16.9 - 26.0 microg/ml) and 14 extracts (75%) were
      able to inhibit at least one of the glycohydrolase enzymes.

PMID- 9180372
TI  - In vitro trans translation mediated by alanine-charged 10Sa RNA.
AB  - 10Sa RNA is a bacterial small stable RNA, in which the 5' and 3'-terminal
      sequences can be folded into a tRNA-like secondary structure which can be
      aminoacylated with alanine. It was found that Escherichia coli 10Sa RNA
      facilitated the incorporation of alanine, tyrosine, aspartic acid and glutamic
      acid, but not valine, isoleucine, serine or arginine, into the growing
      polypeptide in vitro, depending on poly (U)-directed poly-phenylalanine
      synthesis. This result indicates that 10Sa RNA functions as an mRNA for the tag
      peptide which has been found to be attached to the C termini of truncated
      polypeptides synthesized in vivo. Aminoacylation with alanine was required for
      tag-specific amino acid incorporation and for efficient association of 10Sa RNA
      with the ribosome, indicating that 10Sa RNA also functions as an alanine tRNA in
      the tag-peptide synthesis. The dual function of 10Sa RNA both as an mRNA and as a
      tRNA in vitro strongly supports the trans translation hypothesis.

PMID- 9180373
TI  - Structural changes in a secretory phospholipase A2 induced by membrane binding: a
      clue to interfacial activation?
AB  - Activation of phospholipase A2 (PLA2) upon binding to phospholipid assemblies is
      poorly understood. X-ray crystallography revealed little structural change in the
      enzyme upon binding of monomeric substrate analogs, whereas small conformational
      changes in PLA2 complexed with substrate micelles and an inhibitor were found by
      NMR. The structure of PLA2 bound to phospholipid bilayers is not known. Here we
      uncover by FTIR spectroscopy a splitting in the alpha-helical region of the amide
      I absorbance band of PLA2 upon binding to lipid bilayers. We provide evidence
      that a higher frequency component, which is only observed in the membrane-bound
      enzyme, is a property of more flexible helices. Formation of flexible helices
      upon interaction with the membrane is likely to contribute to PLA2 activation.

PMID- 9180374
TI  - A histidine variant of yeast iso-1-cytochrome c that strongly affects the
      energetics of the denatured state.
AB  - Iso-1-cytochrome c has been engineered to remove all histidine residues not
      involved in heme ligation in the native state to produce a variant designated TM.
      Single histidine residues were then introduced at positions 26, TM + His26, and
      54, TM + His54. Since histidine residues not involved in native state heme
      ligation are known to replace the methionine 80 heme ligand in denatured
      cytochrome c, these variants were expected to affect the structure of the
      denatured state. Guanidine hydrochloride denaturations were performed to assess
      the stability of these proteins relative to the wild-type protein. The free
      energy difference for heme ligation in the denatured state was assessed by pH
      titration. The experimentally observed mutation-induced change (delta deltaG(D
      state)) in the free energy of heme ligation for unfolded TM + His54 versus TM +
      His26 is -0.4 kcal/mol. The expected mutation-induced change in delta deltaG(D
      state) calculated for a random coil unfolded state is +2 kcal/mol. Thus, unfolded
      TM + His54 has residual structure stabilizing its denatured state by -2.4
      kcal/mol relative to TM + His26. The results imply that the denatured state can
      contribute significantly to mutation-induced changes in the free energy of
      unfolding of a protein.

PMID- 9180375
TI  - Head morphogenesis genes of the Bacillus subtilis bacteriophage SPP1.
AB  - We have identified and characterized the phage cistrons required for assembly of
      SPP1 heads. A DNA fragment containing most of the head morphogenesis genes was
      cloned and sequenced. The 3'-end of a previously identified gene (gene 6) and
      eight complete open reading frames (7 to 15) were predicted. We have assigned
      genes 7, 8, 9, 11, 12, 13, 14 and 15 to these orfs by correlating genetic and
      immunological data with DNA and protein sequence information. G7P was identified
      as a minor structural component of proheads and heads, G11P as the scaffold
      protein, G12P and G15P as head minor proteins and G13P as the coat protein.
      Characterization of intermediates in head assembly, which accumulate during
      infection with mutants deficient in DNA packaging or in morphogenetic genes,
      allowed the definition of the head assembly pathway. No proteolytic processing of
      any of the head components was detected. Removal of G11P by mutation leads to the
      accumulation of prohead-related structures and aberrant particles which are
      similar to the assemblies formed by purified G13P in the absence of other phage
      encoded proteins. The native molecular masses of G11P and G13P are about 350 kDa
      and larger than 5000 kDa, respectively (predicted molecular masses 23.4 kDa and
      35.3 kDa, respectively). G13P, upon denaturation and renaturation, assembles from
      protomers into some prohead-related structures. The organization of the DNA
      packaging and head genes of SPP1 resembles the organization of genes in the
      analogous regions of phage lambda and P22.

PMID- 9180377
TI  - Protein evolution viewed through Escherichia coli protein sequences: introducing
      the notion of a structural segment of homology, the module.
AB  - Paralogous genes are genes which descend from a progenitor gene which has
      duplicated as an ancestral gene, each copy having diverged prior to speciation.
      With comprehensive information available on functions of Escherichia coli
      proteins, analysis of sequence-related E. coli paralogous proteins can give
      information on the early ancestors of families of proteins now residing in many
      contemporary organisms, such as the enzymes of metabolism, some kinds of
      transport mechanisms and some kinds of regulatory mechanisms. In the first step,
      we have confirmed that E. coli contains a very high proportion of paralogous
      proteins. Next, we have defined two main classes of paralogous proteins. One
      class is formed of proteins which contain a unique structural segment homologous
      to a single set of related proteins. The other class corresponds to proteins
      which contain more than one structural segment of homology, each segment
      homologous to unrelated sets of proteins. We define such an independent
      structural segment of homology as a module. This modular structure (mean length
      equivalent to 209 amino acids) corresponds often to entire proteins, but there
      are also proteins that appear to be assembled from two or three independent
      modules having independent origins. Most multimodular proteins appear to have
      been formed early in their history, a minority appear to be relatively recent
      fusions of independent modules. Examining 1404 independent structural segments of
      homology, composed of both modules and entire proteins, we found that the
      segments of homology fell into 352 sequence-related groups or families. The
      majority of these families (ranging from 2 to 62 members) are functionally
      homogeneous. This strongly suggests that the 1404 present-day modules and
      proteins derive from a minimal set of 352 ancestral modules, each one being
      already of the same size and having a function similar to all members of its
      progeny.

PMID- 9180376
TI  - Initiation of replication of plasmid pMV158: mechanisms of DNA strand-transfer
      reactions mediated by the initiator RepB protein.
AB  - The initiator RepB protein of the rolling circle-replicating plasmid pMV158 has
      nicking-closing (topoisomerase I-like) activities on supercoiled DNA. RepB is
      also able to perform a strand-transfer reaction on a single-stranded DNA
      substrate that contains its target. Several attempts at capturing covalent
      protein-DNA intermediates were made to identify the mechanism of RepB-mediated
      activity. Whereas RepB did not generate stable complexes with its target DNA,
      employment of single-stranded oligonucleotides containing a chiral
      phosphorothioate in the target DNA allowed us to follow the process of RepB
      mediated strand-transfer reaction. This reaction occurred through a number of
      even steps because the chirality of the phosphorothioate at the reaction site was
      retained after RepB-mediated strand transfer. This finding suggests the existence
      of a covalent intermediate during the strand-transfer reaction between the
      protein and its target DNA. By site-directed mutagenesis at the codon for Tyr99
      of RepB, and purification and assay of activity of the mutant protein variants,
      we showed that the Tyr99 residue is involved in the nucleophilic attack of RepB
      to its cognate DNA.

PMID- 9180378
TI  - The crystal structure of seleno-glutathione peroxidase from human plasma at 2.9 A
      resolution.
AB  - Glutathione peroxidase belongs to the family of selenoproteins and plays an
      important role in the defense mechanisms of mammals, birds and fish against
      oxidative damage by catalyzing the reduction of a variety of hydroperoxides,
      using glutathione as the reducing substrate. However, the physiological role of
      human plasma glutathione peroxidase remains unclear due to the low levels of
      reduced glutathione in human plasma and the low reactivity of this enzyme. The
      crystal structure of human plasma glutathione peroxidase was determined by
      Patterson search methods using a polyalanine model modified from the known
      structure of bovine erythrocyte glutathione peroxidase. The structure was refined
      to a crystallographic R-factor of 0.228 (R(free) = 0.335) with I > 2sigma(I)
      reflections in the resolution range of 8 to 2.9 A. The asymmetric unit contains a
      dimer. Tetramers are built up from dimers by crystallographic symmetry. The
      subunit structure of the plasma enzyme shows the typical structure motif of the
      thioredoxin fold consisting of a central beta-sheet and several flanking alpha
      helices. The active site selenocysteine residue is situated in the loop between
      beta1 and alpha1 and is located in a pocket on the protein surface. The overall
      structure of the human plasma enzyme is similar to that of the bovine erythrocyte
      enzyme. The main differences in their subunit structures are an extended N
      terminus and the possible existence of a disulfide bridge in the plasma enzyme.
      Compared to the bovine erythrocyte enzyme, a number of residues in the active
      site are mutated or deleted in the plasma enzyme, including all the residues that
      were previously suggested to be involved in glutathione binding. The observed
      structural differences between the two enzymes suggest differences in substrate
      binding and specificity.

PMID- 9180379
TI  - Structure of neurotoxin B-IV from the marine worm Cerebratulus lacteus: a helical
      hairpin cross-linked by disulphide bonding.
AB  - B-IV is a 55-residue, crustacean-selective, neurotoxin secreted by Cerebratulus
      lacteus, a large marine worm found along the northeastern coast of North America.
      The 3D structure of this molecule in aqueous solution has been determined by 1H
      NMR spectroscopy at 600 MHz. The molecule has a well-defined helical hairpin
      structure, with the branches of the hairpin linked by four disulphide bonds. The
      disulphide connectivities were established from the NMR data to be 1-8/2-7/3-6/4
      5, which differed from those determined previously by chemical means, where 1-7
      and 2-8 connectivities were found. Each branch of the hairpin is largely alpha
      helical, with the helices in the N and C-terminal branches encompassing residues
      11 to 23 and 34 to 49, respectively. The loop connecting the branches of the
      hairpin contains two inverse gamma-turns centred on residues 24 and 25, a type I
      beta-turn at residues 28 to 31 and a type II beta-turn at residues 30 to 33.
      Arg17, -25 and -34, which are important for activity, are all on the same face of
      the molecule, while Trp30, which is also important for activity, is on the
      opposite face. Structure comparisons show that the B-IV structure is quite
      similar to those of Rop (ColE1 repressor of primer) and the heat-stable
      enterotoxin B from Escherichia coli. These structural similarities are discussed
      in relation to possible mechanisms of action of B-IV.

PMID- 9180380
TI  - Structural characterisation and comparison of the native and A-states of equine
      lysozyme.
AB  - Native state 1H NMR resonance assignments for 125 of the 129 residues of equine
      lysozyme have enabled measurement of the hydrogen exchange kinetics for over 60
      backbone amide and three tryptophan indole hydrogen atoms in the native state.
      Native holo equine lysozyme hydrogen exchange protection factors are as large as
      10(6), the most protected residues being located in elements of secondary
      structure. High exchange protection in the domain interface correlates with the
      binding of Ca2+ in this region. Equine lysozyme differs from most non-Ca2+
      binding lysozymes in forming a highly populated partially folded state at low pH.
      The protein in this A-state at pH 2.0 has been found to bind 1-anilino
      naphthalene-8-sulphonate with the enhancement of fluorescent intensity and blue
      shift in the spectral maximum characteristic of molten globules. NMR spectra
      indicate that the A-state is globally much less ordered than native equine
      lysozyme but does not contain significant regions of random coil structure. The
      amides most protected against hydrogen exchange in the A-state (protection
      factors up to 10(2) at 5 degrees C) correspond to residues of three of the four
      alpha-helices of the native state; the side-chains of these residues form a
      hydrophobic cluster that includes five aromatic residues. Circular dichroism and
      tryptophan fluorescence indicate that these residues are substantially more
      constrained than similar residues in "classical" molten globules. Taken together,
      the data suggest a model for the A-state of equine lysozyme in which a more
      ordered core is surrounded by a less ordered but still compact polypeptide chain.

PMID- 9180381
TI  - Solution structure of ferredoxin from the thermophilic cyanobacterium
      Synechococcus elongatus and its thermostability.
AB  - The three-dimensional structure of ferredoxin, purified from the thermophilic
      cyanobacterium Synechococcus elongatus, was determined in aqueous solution by two
      dimensional proton nuclear magnetic resonance. In addition to the 946 distance
      constraints from nuclear Overhauser effect connectivities, we added 241 distance
      constraints derived from the crystal structure of Spirulina platensis ferredoxin
      to the 19 residues close to the [2Fe-2S] iron-sulfur center, where crosspeaks
      disappeared due to paramagnetic effects. The atomic root-mean-square difference
      of the ten converged structures from the mean structure was 0.61(+/-0.12) A for
      backbone atoms (N, C(alpha), C'). The main-chain structure was almost the same as
      the crystal structures of other mesophile ferredoxins, but comparison of the side
      chain structures revealed an extension of the hydrophobic core, a unique
      hydrophobic patch on the surface of the large beta-sheet, and two unique charge
      networks in this thermostable ferredoxin structure, some of which might
      contribute to thermostability.

PMID- 9180382
TI  - The rational construction of an antibody against cystatin: lessons from the
      crystal structure of an artificial Fab fragment.
AB  - In a protein design study the artificial antibody M41 was modelled with its
      binding site complementary to the protease inhibitor cystatin, which was chosen
      as a structurally well-characterized "antigen". The modelling of M41 took
      advantage of the crystal structure of the anti-lysozyme antibody HyHEL-10 as a
      structural template. Its combining site was reshaped by replacing 19 amino acid
      side-chains in the hypervariable loops. In addition, ten amino acid residues were
      substituted in the framework regions. The crystal structure of the corresponding
      antibody model M41, which was produced as an F(ab) fragment in Escherichia coli,
      was determined at a resolution of 1.95 A. The crystals exhibited symmetry of the
      space group P2(1)2(1)2(1) (a = 96.5 A; b = 103.5 A; c = 113.6 A) with two F(ab)
      fragments in the asymmetric unit, which were independently refined (final R
      factor 21.7%). The resulting coordinates were used for a detailed comparison with
      the modelled protein structure. It was found that the mutual arrangement of the
      six complementarity-determining regions as well as most of their backbone
      conformation had been correctly predicted. One major difference that was detected
      for the conformation of a five residue insertion in complementarity-determining
      region L1 could be explained by an erroneously defined segment in the structure
      of the antibody 4-4-20, which had been used as a template for this loop. In the
      light of more recent crystallographic data it appears that this segment adopts a
      new canonical structure. Apart from this region, most of the side-chains in the
      antigen-binding site had been properly placed in the M41 model. There was however
      one important exception concerning Trp H98, whose side-chain conformation had
      been kept as it appeared in HyHEL-10. The differing orientation of this residue
      in the model compared with the crystal structure of the artificial F(ab) fragment
      M41 explains why an antigen affinity could not be detected so far. The detailed
      analysis of this and other, more subtle deviations suggests how to make this
      F(ab) fragment function by introducing a few additional amino acid changes into
      M41.

PMID- 9180384
TI  - Enhanced immunostimulation by novel platinum anticancer agents.
AB  - 'Poly-plat', SSP and SAP are second generation analogs of cisplatin which have
      been shown to activate murine peritoneal macrophages in vivo and in vitro. Murine
      peritoneal macrophages treated with 'poly-plat', SSP or SAP (5 microg/mg) for 2 h
      are stimulated to form cytoplasmic extensions. Drug-treated macrophages also
      elicit an increase in the number of lysosomes. In addition, analysis of tissue
      culture supernatants shows increased levels of interleukin-1alpha and tumor
      necrosis factor-alpha. These results show that 'poly-plat', SSP and SAP enhance
      the immune system with greater efficacy and potency than cisplatin.

PMID- 9180383
TI  - Efficacy of oral irinotecan against neuroblastoma xenografts.
AB  - The efficacy of the topoisomerase I inhibitor, 7-ethyl-10-(4-[1-piperidino]-1
      piperidino)-carbonyloxy-camptotheci n (irinotecan, CPT-11), administered by oral
      gavage has been examined against a panel of six independently derived
      neuroblastoma xenografts. Irinotecan was administered either daily for 5 days on
      12 consecutive weeks ?(d x 5)12? or for 5 days on two consecutive weeks repeated
      every 21 days for 4 cycles ?[(d x 5)2]4?. Given on the (d x 5)12 schedule the
      maximum tolerated dose (MTD) was 50 mg/kg. For intermittent scheduling ?[(d x
      5)2]4?, the MTD was 75 mg/kg, resulting in the same total dose being administered
      (3 g/kg) over the period of treatment. At the MTD for the 12 consecutive week
      schedule there were two of 42 toxicity related deaths, whereas intermittent
      scheduling at the MTD resulted in none of 42 deaths. The intermittent schedule
      ?[(d x 5)2]4? was less toxic than therapy given (d x 5)12, as at the end of
      treatment mice weighed 92 +/- 4% (SD; n = 6 experiments) and 81 +/- 4% (SD; n = 6
      experiments) of their body weight at the start of therapy, respectively. The
      latter schedule was associated with loose feces starting around week 8 of
      therapy, broken teeth and a high incidence of swelling of the orbital conjunctiva
      that developed late in the course of therapy. Given (d x 5)12, irinotecan caused
      complete regressions of all six neuroblastoma xenograft lines. Because mice
      tolerate significantly greater systemic exposure to SN-38 lactone than do
      patients (as determined by plasma AUC at the respective MTD), we evaluated the
      intermittent schedule of administration, reducing the dose/administration to
      determine the lowest dose levels that produced objective regressions of these
      neuroblastoma xenografts and determined the daily systemic exposure associated
      with these dose levels. In four lines examined objective responses were obtained
      at dose levels of 12.5 or 6.25 mg/kg. The daily plasma AUC exposures associated
      with minimum dose achieving response in NB1691 (12.5 mg/kg), NB1643 (6.25 mg/kg)
      and NBEB (12.5 mg/kg) for irinotecan lactone were 219, 152 and 653 ng-h/ml,
      respectively; and for SN-38 lactone were 704, 418 and 987 ng-h/ml, respectively.
      These results indicate that childhood neuroblastoma xenografts are highly
      sensitive to irinotecan given by oral administration and therapeutic activity is
      similar to i.v. irinotecan administered on similar schedules.

PMID- 9180385
TI  - Elimination of adult T cell leukemia cells by ultrasound in the presence of
      porfimer sodium.
AB  - Sonodynamic effects using porfimer sodium (Photofrin; Pf) on leukemic and normal
      cells were evaluated. The purpose of this experiment was to compare cell survival
      among MT-2 cells, normal peripheral mononuclear cells (PMNCs) and adult T cell
      leukemia (ATL) patients' PMNCs after sonodynamic treatment. Cells were exposed to
      450 kHz ultrasound at an intensity of 500 mW/cm2. The survival rate of MT-2 cells
      exposed to ultrasound alone for 80 s was 20.1 +/- 4.8%, whereas survival rates
      exposed to ultrasound in combination with 25, 50 and 100 microg/ml of Pf resulted
      in 11.5 +/- 2.9, 3.2 +/- 1.6 and 1.6 +/- 1.4%, respectively. There was a
      significant difference of cell survival between the group exposed to ultrasound
      alone and the Pf-combined groups (n = 6, p < 0.05). On the other hand, in the
      normal human PMNCs, no significant differences of cell survival rates were found
      between ultrasound-treated groups with and without Pf. We similarly examined the
      survival rate of PMNCs in the peripheral blood of five acute-type ATL patients (n
      = 5) after ultrasound (60 s, 300 mW/cm2) exposure with or without 100 microg/ml
      of Pf. Comparison of cell survival rate between ultrasound alone and ultrasound
      plus Pf showed significant differences (69.4 +/- 22.5 and 30.0 +/- 23.0%,
      respectively). There were no significant cytotoxicities in all Pf alone treated
      groups of the MT-2 cells, the normal PMNCs and the ATL patients' PMNCs (p <
      0.05). It was suggested from this study that there was a specific selectivity of
      sonodynamic effects to MT-2 cell lines and ATL patients' PMNCs. It is anticipated
      that this new method of treatment, i.e. sonodynamic therapy, could be used for
      extracorporeal blood treatment of acute-type ATL patients.

PMID- 9180386
TI  - Surface plasmon resonance analysis of topoisomerase I-DNA binding: effect of Mg2+
      and DNA sequence.
AB  - Surface plasmon resonance detection was used to characterize interactions of
      human topoisomerase I and DNA. The disassociation of topoisomerase I and DNA is
      characterized by two rate constants. This suggests two parallel but independent
      pathways of release. DNA association appears to be complex. Mg2+ was found to
      increase both disassociation rate constants and may have a detectable effect on
      topoisomerase I-DNA association. DNA base content did not affect disassociation
      rate constants or the rate of association.

PMID- 9180387
TI  - Activity of TER286 against human tumor colony-forming units.
AB  - Glutathione S-transferase (GST) isozymes have been shown to be elevated in many
      human cancer types as compared to normal tissues. TER286, one in a class of
      glutathione-based GST-activated cytotoxins, was tested in a soft agar cloning
      assay to determine its in vitro activity against primary human tumor colony
      forming units. Breast and lung specimens from patients who had received prior
      therapy and those who were previously untreated were exposed to TER286 at
      concentrations of 1, 10 and 50 microM using both 1 h and continuous exposures.
      Overall in vitro responses (50% or less survival compared to untreated controls)
      were observed in 0% (0/14), 14% (2/14) and 29% (4/14), respectively, in specimens
      exposed to TER286 for 1 h, and in 5% (2/41), 10% (4/41) and 61% (25/41),
      respectively, in specimens exposed to TER286 continuously. TER286 has cytotoxic
      activity against both breast and lung cancer colony-forming units, and
      demonstrates a concentration-response effect. At 50 microM, there is a
      significant difference between 1 h and continuous exposures in head-to-head
      comparisons. These data suggest that TER286 can be activated in human tumor
      colony-forming units and should be pursued as a treatment candidate for patients
      whose tumors are resistant to drug treatment based on up-regulation of GST.

PMID- 9180389
TI  - Pilot phase I-II study on 5-aza-2'-deoxycytidine (Decitabine) in patients with
      metastatic lung cancer.
AB  - 5-Aza-2'-deoxycytidine (5-AZA-CdR, Decitabine) is a nucleoside analog and an
      active drug for the therapy of acute leukemia. The incorporation of 5-AZA-CdR
      into DNA blocks DNA methylation and can result in the activation of specific
      genes, such as tumor suppressor genes. This novel mechanism of action of 5-AZA
      CdR stimulated our interest in its potential for cancer therapy in patients with
      lung cancer. Using a colony assay we observed that 5-AZA-CdR showed a potent
      antineoplastic effect against two human lung carcinoma cell lines. The objective
      of this preliminary phase I-II study was to evaluate the toxicity and clinical
      efficacy of 5-AZA-CdR in patients with stage IV non-small cell lung carcinoma.
      There were 15 patients that entered the clinical study. For nine assessable
      patients that received 5-AZA-CdR by a single 8 h i.v. infusion of 200-660 mg/m2
      for one or more cycles, the median survival duration was 6.7 months, with three
      patients surviving more than 15 months. The steady-state plasma concentration of
      5-AZA-CdR during the infusion was estimated in some patients and was in the same
      range that produced activation of a tumor suppressor gene in human lung tumor
      cell lines as reported by other investigators. The major side effect of 5-AZA-CdR
      was hematopoietic toxicity which required a 5-6 week recovery period before the
      next cycle of therapy. This study suggests that 5-AZA-CdR may have some clinical
      activity against metastatic lung carcinoma using this type of dose schedule.

PMID- 9180388
TI  - The effect of ethyldeshydroxy-sparsomycin and cisplatin on the intracellular
      glutathione level and glutathione S-transferase activity.
AB  - Ethyldeshydroxy-sparsomycin (EdSm) is a ribosomal protein synthesis inhibitor
      which synergistically enhances the antitumor activity of cisplatin against L1210
      leukemia in vivo. Because cellular glutathione (GSH) and glutathione S
      transferases (GST) are reported to interfere with the antitumor activity of
      cisplatin, we analyzed the effect of EdSm and cisplatin on GSH and GST activity
      in selected tumor cells. For this purpose we used three murine leukemia tumors
      with different sensitivities towards EdSm and cisplatin: L1210-WT, sensitive to
      both drugs, L1210-Sm, resistant to EdSm, and L1210-CDDP, resistant to cisplatin.
      No significant differences were detectable between these three cell lines
      regarding the population doubling time, the cell size, and the cellular level of
      protein and glutathione. Neither of the resistant L1210 subclones showed P
      glycoprotein expression. Drug exposure, however, changed the intracellular
      dynamics. Exposure to EdSm strongly decreased the amount of cellular protein,
      decreased the overall GST activity and led to GSH depletion, whereas exposure to
      cisplatin induced a rise in the amount of protein, in GSH, and in the total GST
      activity. These effects are dose-dependent and correlate well with the
      sensitivity of the tumor cells for EdSm or cisplatin. In addition, exposure to
      EdSm lowered the V(max) of GST in L1210-WT and L1210-Sm; however, in L1210-CDDP
      both the V(max) and the K(m) were increased. That this was not a direct effect of
      EdSm on GST was shown in a cell-free system, where EdSm did not influence the GST
      activity nor could it act as a substrate for GST. Our results suggest that the
      synergistic combination of EdSm and cisplatin might be explained by EdSm
      switching off the cellular detoxification mechanism for cisplatin, i.e. by
      inhibition of de novo synthesis and subsequent depletion of GSH and GST.

PMID- 9180390
TI  - The inhibition of growth and down-regulation of gonadotropin releasing hormone
      (GnRH) receptor in alphaT3-1 cells by GnRH agonist.
AB  - Gonadotropin releasing hormone (GnRH) and its analogs inhibit the growth of
      hormone-dependent tumors in vivo and in vitro. The inhibition of growth and
      proliferation of tumor cells in vitro by GnRH and its analogs indicates that the
      tumor suppressing effect of the hormone is only partially due to suppression of
      pituitary gonadotropin release which reduces circulating steroid levels that are
      required for proliferation. Demonstration of GnRH-binding sites on some tumors
      suggests a direct inhibitory effect of GnRH and its analogs. However, the
      mechanism by which GnRH and its analogs inhibit tumor cell growth is not known.
      Our hypothesis is that the inhibition of growth and proliferation of tumor cells
      by GnRH and its analogs are mediated through down-regulation of its receptor
      expression. To test this hypothesis, mouse pituitary gonadotrope cell line
      (alphaT3-1) was selected as a model since this is the only cell line which
      expresses a sufficiently high level of GnRH receptors for precise measurements of
      the mRNA for the receptor. Addition of GnRH agonist (D-Lys6)GnRH to the cell
      cultures caused a time-dependent decrease in both cell growth, as measured by
      cell number, and cell proliferation, as measured by [3H]thymidine incorporation
      into DNA. After 1 h of treatment of alphaT3-1 cells with 1 microM of (D
      Lys6)GnRH, the cell number was reduced to 83.0 +/- 13.4 compared to control,
      decreased to 75.1 +/- 3.2 at 2 h, 63.2 +/- 0.66 at 4 h and 52.2 +/- 0.87 at 24 h.
      This decrease in cell number was accompanied by a parallel decrease in
      [3H]thymidine incorporation into DNA. The inhibition of cell growth and
      [3H]thymidine incorporation by treatment with 1 microM of (D-Lys6)GnRH was
      sustained for at least 72 h. Inhibition of alphaT3-1 cell growth and
      [3H]thymidine incorporation was dose-dependent; thus 10(-9) M (D-Lys6)GnRH
      resulted in about 30% inhibition within 4h which was comparable to 10(-6) M (D
      Lys6)GnRH, whereas 10(-12) M (D-Lys6)GnRH was ineffective. Measurement of mRNA
      for the GnRH receptor by Northern blot analysis showed a decrease in levels of
      mRNA by 5% within 2 h of treatment of alphaT3-1 cells with 1 microM (D-Lys6)GnRH,
      by 30% at 4 h and by 50% at 24 h. In conclusion these data demonstrate that
      treatment of alphaT3-1 cells with (D-Lys6)GnRH causes an inhibition of cell
      growth and proliferation, and down-regulates the GnRH receptor mRNA levels.

PMID- 9180391
TI  - CNF combination as adjuvant treatment in breast cancer patients is well
      tolerated.
AB  - In this study 194 women with breast cancer received adjuvant CNF combination
      therapy (cyclophosphamide, mitoxantrone and 5-fluorouracil). The side effects and
      acute toxicity of the regimen were recorded. Although myelosuppression is the
      dose-limiting factor of the CNF regimen, it was well tolerated and side effects
      were limited. This regimen induced no cardiotoxicity or irreversible alopecia. It
      is concluded that CNF is suitable as adjuvant chemotherapy for breast cancer
      patients.

PMID- 9180392
TI  - Effects of prolonged versus short-term exposure paclitaxel (Taxol) on human tumor
      colony-forming units.
AB  - Paclitaxel shows a broad clinical activity in ovarian, breast and non-small cell
      lung cancers. However, controversy remains about the respective effects of doses
      and schedules in paclitaxel cytotoxicity. This study was conducted to compare the
      cytotoxic activity of short-term (1 h) versus prolonged exposure (14 days) to
      paclitaxel in human cancer cells. A soft-agar cloning system assay was used to
      determine the in vitro effects of 0.025-25.0 microg/ml paclitaxel against cancer
      cells taken directly from patients. A decrease in tumor colony formation
      resulting from drug exposure was considered an in vitro response if survival of
      colonies was up to 50% of that in positive controls. Among 11 evaluable patients'
      biopsies, both short- and long-term exposure to paclitaxel had significant
      concentration-dependent effects on the growth inhibition of human cancer cells.
      With the 1 h exposure schedule, in vitro responses were observed in 9,18 and 64%
      of evaluable tumor specimens at final concentrations of 0.25, 2.5 and 25.0
      microg/ml, respectively. With the prolonged exposure schedule, concentrations of
      0.25, 2.5 and 25.0 microg/ml induced 27, 45 and 91 in vitro response rates,
      respectively. In those patients' biopsies prolonged exposure to paclitaxel
      induced significantly more in vitro tumor responses than 1 h administration (p <
      0.01). Similar trends were observed in ovarian, breast and non-small cell lung
      cancers. Our data indicate that the duration of exposure to paclitaxel is an
      important factor in paclitaxel cytotoxicity in human tumors and suggest that long
      term exposure may improve the antitumor activity of paclitaxel.

PMID- 9180393
TI  - Therapeutic and imaging capacity of tumor-localizing radiosensitive Mn-porphyrin
      on SCCVII tumor-bearing C3H/He mice.
AB  - We synthesized a radiosensitizer KADTF, consisting of a hypoxic radiosensitizer,
      KU2280, bound to the side chain group of Mn-metalloporphyrin, which accumulates
      in tumor tissue. In the in vitro colony-forming activity test using HeLa cells,
      KADTF enhanced the effect of radiation under hypoxic conditions. Radiation
      therapy at 20 Gy, 1.5 h after infusion of KADTF (0.15 mM/kg), inhibited tumor
      growth more markedly than did a single radiation treatment. A clear tumor MR
      images of the SCCVII tumor was obtained at 1.5 h after administration of KADTF
      (0.1 mM/kg).

PMID- 9180394
TI  - Drug interactions of 5-fluorouracil with either cisplatin or lobaplatin--a new,
      clinically active platinum analog in established human cancer cell lines.
AB  - Lobaplatin [1,2-diaminomethylcyclobutane platinum(II)-lactate] is a new platinum
      compound which appears to possess incomplete cross-resistance to cisplatin and
      might have a favorable pattern of side effects. Since lobaplatin has activity in
      esophageal cancer, combination protocols with 5-fluorouracil (5-FU) are
      evaluated. In order to assess the mode of action of lobaplatin when combined with
      5-FU, two human cancer cell lines were treated with various combinations of 5-FU
      given for either 2 or 24h and lobaplatin. Drug interactions were evaluated by
      isobologram analysis. Lobaplatin showed basically the same interaction pattern
      when combined with 5-FU as cisplatin. The combination of either platinum analog
      with a 24 h exposure to 5-FU was superior to a short-term 5-FU exposure.
      Furthermore, when 5-FU was given for 24 h, no additional effect of folinic acid
      was seen. From these data we conclude that cisplatin and lobaplatin show similar
      interactions with 5-FU. Protracted infusion schedules of 5-FU appear to be more
      active than bolus application.

PMID- 9180395
TI  - A phase II trial of paclitaxel and weekly 24 h infusion of 5-fluorouracil/folinic
      acid in patients with advanced gastric cancer.
AB  - A phase II trial was performed to evaluate the efficacy and toxicity of the
      combination of paclitaxel and 5-fluorouracil (5-FU)/folinic acid in patients with
      advanced gastric carcinoma. Twenty-two patients (six female and 16 male) with
      advanced or metastatic disease were enrolled. None of them had received prior
      chemotherapy. Paclitaxel was administrated as a 3 h infusion of 175 mg/m2 at days
      1 and 22, 5-FU 2000 mg/m2 i.v. over 24 h and folinic acid 500 mg/m2 i.v. 2 h
      prior to 5-FU weekly from days 1 to 36. Seven patients (32%) had partial
      remissions including the lungs, skin, lymph nodes and locally advanced primary
      tumor. The median overall survival was 11 months (range 1-17+) and the median
      progression-free interval was 8 months (range 1-13+). Neutropenia (WHO grade
      III/IV) occurred in 14% of patients. Other main toxicities were alopecia in 45%,
      fever/infection in 9%, and nausea/vomiting and diarrhea in 5%. In conclusion, the
      combination of paclitaxel and continuously infused 5-FU/folinic acid appears to
      be an active regimen for advanced gastric carcinoma with a remission rate
      comparable to ELF or FAMtx. The moderate toxicity allows treatment on an
      outpatient basis.

PMID- 9180396
TI  - Effect of SDZ PSC 833 ([3'-keto-Bmt1]-[Val2]-cyclosporin) on serum protein
      binding and distribution to blood cells of doxorubicin, vincristine and etoposide
      in vitro.
AB  - SDZ PSC 833 ([3'-keto-Bmt1]-[Val2]-cyclosporin) is a P-glycoprotein-mediated
      multidrug resistance modulator currently undergoing clinical trials. SDZ PSC 833
      modulates not only antitumor activity but also tissue distribution of doxorubicin
      in mice. Since protein binding in plasma/serum and distribution to blood cells
      are important factors affecting the tissue distribution and excretion of drugs,
      we investigated the effect of SDZ PSC 833 on serum protein binding and
      distribution to blood cells of doxorubicin, vincristine and etoposide in vitro.
      Unbound fractions in serum and fractions distributed to blood cells of either
      [14C]doxorubicin, [3H]vincristine or [3H]etoposide were determined using serum
      and blood obtained from mice and healthy volunteers. Effects of SDZ PSC 833 at 3
      microg/ml, which was an achievable concentration in a clinical trial of SDZ PSC
      833, on protein binding and distribution of the drugs to blood cells were
      negligible in mouse and human blood in vitro. The absence of interaction between
      PSC 833 and the anticancer drugs in protein binding and distribution to blood
      cells suggested the existence of other mechanisms. Possible interactions are
      speculated to be inhibition of P-glycoprotein function contributing to drug
      excretion and tissue distribution and inhibition of drug metabolism mediated by
      cytochrome P450 3A.

PMID- 9180397
TI  - Word theft.

PMID- 9180398
TI  - The reality of nonscience-based newsletters.

PMID- 9180399
TI  - An objective view of the June editorial.

PMID- 9180400
TI  - More about the nonscience-based newsletters editorial.

PMID- 9180401
TI  - Dentinal bonding agents versus glass-ionomer cements.
AB  - The long-term bonding of dental material to dentin remains an area of great
      controversy and the results of in vitro testing do not always reflect those found
      in vivo. The clinician is faced with a large number of dentinal bonding agents
      that have had limited testing in vivo and are frequently replaced before any long
      term clinical testing has been completed. Glass-ionomer cements, although having
      a longer history of good adhesion to dentin, are not suitable for use in high
      stress-bearing areas. The selection of materials for specific clinical situations
      has become more and more difficult. This paper gave a personal view of the
      history and evolution of both resin bonding agents and glass-ionomer cements and
      their potential in clinical use.

PMID- 9180402
TI  - Combining resin composite bonding and enamel microabrasion.
AB  - Some teeth can best be treated by a combination of enamel microabrasion and resin
      composite bonding. This article outlines a protocol for treating patients with
      such teeth and documents one case, showing 5-year results.

PMID- 9180403
TI  - Reducing the risk of sensitivity and pulpal complications after the placement of
      crowns and fixed partial dentures.
AB  - Sensitivity after cementation of a crown with glass-ionomer cement is often
      attributed to an adverse effect on the pulp by the luting agent. Most permanent
      restorative materials in common use today do not tend to irritate the pulp; the
      main cause of pulpal damage is infection, the bacteria originating in the smear
      layer or deep in the dental tubules, inaccessible to caries-excavating
      procedures. A poorly fitting provisional crown may expose cut dentin to the oral
      fluids, and mechanical trauma caused by frictional heat during preparation may
      also damage the pulp. The following precautions are recommended during
      precementation procedures to reduce the risk of an inflammatory response in the
      pulp: (1) The provisional crown should be well fitting, covering cervical dentin
      but not impinging on the periodontal tissues. The permanent crown should be
      cemented as soon as possible. (2) The superficial smear layer should be removed
      and the dentinal surface should be treated with an antibacterial solution before
      the provisional crown is placed. (3) To decrease dentinal permeability under the
      provisional crown, the dentinal surface should be covered with a liner that can
      be easily removed before final cementation. (4) to ensure optimal mircomechanical
      bonding, the dentinal surface should be thoroughly cleaned, and the dentin should
      be kept moist until cementation. (5) The occlusion should be carefully checked
      before cementation of the crown.

PMID- 9180404
TI  - Retrievable cemented crown options on implant-supported angled abutments: a case
      report.
AB  - Nonaxial implant alignment often predicates the use of cemented of screw-retained
      angled abutments with inherent disadvantages, including reduced retrievability on
      screw loosening. The purposes of this article are to review the relative merits
      of cemented and screw-retained angled abutments and to present a method of
      ensuring retrievability of cemented angled abutments.

PMID- 9180405
TI  - Latex elastic-induced periodontal damage: a case report on the subsequent
      orthodontic management.
AB  - Proper management of a malocclusion relies on a basic understanding of the
      development of the dentition and the craniofacial complex. Diagnosis should only
      be formulated after all the relevant diagnostic records, including clinical
      examination and history, are reviewed. Armed with this information, the dentist
      forms the treatment plan. The mere occurrence of a malocclusion does not
      constitute a need for treatment. Injudicious intervention can be
      counterproductive or destructive. Through a case report, the deleterious effects
      of improper case management and questionable treatment mechanics are highlighted.
      The subsequent orthodontic management emphasizes the principles and techniques
      for the successful treatment of the patient in question.

PMID- 9180406
TI  - Intentional replantation for iatrogenic perforation of the furcation: a case
      report.
AB  - Intentional replantation is an accepted endodontic procedure for treatment of
      teeth in which conventional surgical endodontic treatment is contraindicated.
      This article presents a rare case of intentional replantation of a mandibular
      molar that had severe periodontal destruction resulting from iatrogenic
      perforation of the furcation. A 17-month follow-up evaluation revealed an
      asymptomatic and functional tooth with no radiographic signs of pathosis. The
      favorable results obtained might be attributed to the preservation of the
      vitality of the periodontal ligament; the absence of damaging pressure during
      extraction; the minimal extraoral treatment time; the use of nonrigid splinting;
      and the immediate repair of the perforation during a one-visit endodontic
      procedure. The results obtained with this tooth may indicate the possibility of a
      successful surgical technique for this otherwise hopeless complication of
      endodontic therapy.

PMID- 9180407
TI  - An effective treatment for chronic periodontal abscesses.
AB  - In the past, chronic periodontal abscess was treated by conventional
      gingivectomy, flap access procedures, or by extraction of the affect tooth. A
      modified technique for the treatment of the chronic periodontal abscess is
      described. A surgical approach is combined with root conditioning with
      doxycycline. Application of this technique has resulted in rapid, uneventful
      healing in which neither further tissue breakdown or recurrence of the abscess
      has occurred.

PMID- 9180408
TI  - Stress concentration in all-ceramic posterior fixed partial dentures.
AB  - Two-dimensional finite-element analysis was used to study levels and distribution
      patterns of stress within three-unit fixed partial dentures (mandibular first
      premolar to first molar) constructed of different materials (Type III gold alloy,
      Dicor, and In-Ceram) and with different connector heights (3.0 mm versus 4.0 mm).
      In the computer models, 10 MPa of stress was applied centrally to the prosthesis.
      Resultant von Mises stresses were concentrated within the connectors; the
      greatest stress occurred at the axial location of the connector. Stresses were
      40% to 50% lower for 4.0-mm connectors. Patterns of stress distribution were
      similar for premolar and molar connectors. Stress levels within In-Ceram models
      were lower than for the other two materials and represented a lower percentage of
      the ultimate strength of the material. Based on a two-dimensional finite-element
      analysis model, In-Ceram would appear to be the best choice for posterior fixed
      partial dentures.

PMID- 9180410
TI  - Experimental investigation of the shear strengths of teeth in the region of the
      dentinoenamel junction.
AB  - The shear strengths of human incisors, canines, premolars, and molars and bovine
      incisors in the region of the dentinoenamel junction were tested. The median
      shear strength of all human teeth, 38.99 MPa, was not significantly different
      from that of bovine teeth, 37.40 MPa. Among the groups of human teeth, the
      highest median shear strength was obtained from mandibular premolars (46.15 MPa),
      and the lowest from mandibular canines (32.63 MPa). Physical treatments (cooling
      or drying) led to a significant reduction in shear strengths. A similar effect
      was found after exposure to amino butyrate (a caries-removing agent) but not
      after exposure to sodium hypochlorite (used in endodontic treatment). In all
      investigated groups of teeth, the fracture areas were mainly in dentin and never
      exactly at the dentinoenamel junction; indicating that the cohesion of dentin,
      not the adhesion between dentin and enamel, is the limiting factor in the shear
      strength.

PMID- 9180409
TI  - An in vivo study of a clinical surfactant used with poly(vinyl siloxane)
      impression materials.
AB  - The aim of this study was to determine whether the use of a topical surfactant
      (Hydrosystem), designed for clinical use, improved the quality of the impression
      surface of two poly(vinyl siloxane) materials used in vivo. Before impressions
      were taken, Hydrosystem was applied to the maxillary left or right premolar
      teeth, allocated at random, in 50 subjects. The untreated side acted as a control
      for each subject. The impressions were examined for quality of reproduction and
      number of surface defects. Hydrosystem was found to significantly improve the
      quality of reproduction.

PMID- 9180411
TI  - Conflicts of interest.

PMID- 9180412
TI  - Glass-ionomer cement restorations and secondary caries.

PMID- 9180413
TI  - Glass-ionomer cement restorations.

PMID- 9180414
TI  - Esthetic management of congenitally missing lateral incisors with single-tooth
      implants: a case report.
AB  - Achievement of an esthetic single-tooth restoration in the anterior segment is a
      difficult task for the restorative dentist. A case is described in which two
      congenitally missing maxillary lateral incisors were replaced with single-tooth
      implants. A new technique was used to restore the teeth provisionally with a
      polyethylene ribbon and resin replacement. Light-cured staining systems for
      acrylic resins and ceramics were employed to customize both the provisional and
      final restorations.

PMID- 9180415
TI  - Comparison of stress distribution around vertical and angled implants with finite
      element analysis.
AB  - The distribution of stress around implants placed in the first molar region of
      the mandible was biomechanically analyzed in a two-dimensional mathematical
      model. Two types of implants, vertical and angled, were subjected to a vertical
      load of 100 N and a horizontal load of 50 N in turn. The magnitudes and contours
      of compressive and tensile stress within the surrounding bone were determined.
      For the sake of comparison, maximal compressive stress and maximal tensile stress
      at the surrounding bone were calculated. There were no measurable differences in
      stress values and contours when a horizontal load was applied to the vertical and
      angled implants. However, with the vertical loading, the compressive stress
      values were five times higher around the cervical region of the angled implant
      than around the same area in the vertical implant.

PMID- 9180416
TI  - Prosthetic management for edentulous glossectomy patients.
AB  - The prosthetic treatment of edentulous glossectomy patients is very difficult.
      The tongue defect results in oral dysfunction and affects the stability of the
      mandibular denture. The appropriate denture form and occlusion can be established
      by using the modified functional impression technique. Through the use of x-ray
      television and an image-processing system in clinical experiments, it was shown
      that a wide buccolingual table, an occlusal table height matched to that of the
      tongue body, and close adherence of the tongue and the lingual flange are
      effective means of preventing food from dropping to the oral floor, keeping the
      food on the occlusal table, and crushing the food.

PMID- 9180417
TI  - Anterior implant-supported overdentures.
AB  - Retention of complete mandibular dentures can be successfully achieved by means
      of an implant-retained or natural tooth-retained bar and clip system in the
      anterior segment of the mandible. The same design principles hold true for both
      methods of anchoring the retentive bar. These retentive elements must be
      constructed to allow some freedom of movement around a fulcrum line designed to
      be perpendicular to the sagittal plane.

PMID- 9180418
TI  - Direct access to equivocal approximal carious lesions.
AB  - Approximal carious lesions provide unique diagnostic and restorative challenges
      for clinicians interested in conserving tooth structure. Direct access reduces
      diagnostic doubt and facilitates optimal restorative management. The direct
      access afforded to newly erupted posterior teeth provides an incomparable window
      of opportunity to the proximal surfaces. Optimal management is limited to the
      interval between exfoliation and eruption, because access is lost once the
      erupting adjacent permanent teeth come into contact. Diagnostic and restorative
      strategies accomplished after creation of direct access to approximal lesions are
      discussed.

PMID- 9180419
TI  - Clinical considerations for optimal dentinal bonding.
AB  - A review of current clinical research has demonstrated that successful attachment
      with resin-based bonding systems is achieved through brief acidic conditions of
      dentin, followed by thorough coverage with resin priming and bonding agents. This
      article discusses factors of clinical relevance in achieving optimal results.
      Effective priming, using multiple coats to enhance resin penetration to the full
      depth of dentinal demineralization, is crucial. A thin, uniform layer of bonding
      resin is a critical, elastic intermediary for absorbing stresses of
      polymerization shrinkage. An air stream should be used only for evaporation of
      solvent and not for spreading bonding resin, because use of an air stream causes
      uneven thinning of this valuable intermediate layer. Contamination of the
      dentinal surface with excessive moisture or solvent or the presence of air voids
      will make bonding unpredictable under clinical conditions. Adequate etching of
      peripheral enamel continues to be an important factor in the long-term retention
      of adhesive restorations.

PMID- 9180420
TI  - Clinical performance of preventive resin restorations placed in a hospital
      environment.
AB  - This study was conducted retrospectively to evaluate the clinical performance of
      preventive resin restorations. Five hundred thirty-two restorations in 351
      patients had been in the mouth for a mean of 16.5 %/- 7.6 months. The clinical
      performance was determined with a modified version of the US Public Health
      Service rating system. In 79.9% of the restorations, the marginal discoloration
      was rated as Alfa (no discoloration), while only 0.9% were scored as Charlie
      (discoloration penetrating in a pulpal direction). The marginal adaptation was
      rated as Oscar (fully sealed) in 28.4% of restorations; in only 0.4% of
      restorations, rated as Charlie or Delta, was the dentin or base exposed. In 98.3%
      of the restorations evaluated, the anatomic form was rated as Alfa (continuous
      with existing anatomic form). Recurrent caries was associated with 2.3% of the
      restorations. Chi-squared tests failed to reveal any statistically significant
      relationships between the clinical performance of the restorations and the length
      of time in the mouth.

PMID- 9180421
TI  - A fluoride release-adsorption-release system applied to fluoride-releasing
      restorative materials.
AB  - This investigation compared the initial fluoride release and release following
      refluoridation of three resin-modified glass-ionomer cements (Photac-Fil
      Applicap, Vitremer, and Fuji II LC) and a new polyacid-modified resin composite
      material (Dyract). After daily flouride release was measured for 8 days,
      specimens were refluoridated in 1,000-ppm solutions of fluoride ion for 10
      minutes and fluoride release was measured for 5 days. Two further 5-day
      refluoridation-release periods were carried out. All materials released fluoride
      initially. Photac released the most; Dyract released the least. Initial release
      was greatest over the first few days. All materials released significantly more
      fluoride for 24 to 48 hours after refluoridation. Less fluoride was released with
      each successive refluoridation for the three glass-ionomer cements. The release
      from the Dyract compomer remained at a comparatively constant and significantly
      lower level following each refluoridation.

PMID- 9180422
TI  - Radiopacity of resin-modified glass-ionomer restorative cements.
AB  - This in vitro study compared the relative radiopacities of three commercially
      available resin-modified glass-ionomer cements (Vitremer, Fuji II LC, and Photac
      Fil), an experimental resin-modified glass-ionomer (V-66), two conventional glass
      ionomers (ChemFil and Fuji Cap II), and amalgam (as the control). Radiopacity was
      assessed densitometrically and expressed as equivalent thicknesses of aluminum.
      All the glass-ionomer cements were more radiopaque than enamel and dentin, with
      the exception of ChemFil and Photac-Fil. Apart from the control material, the
      experimental resin-modified glass-ionomer material, V-66, had the highest
      radiopacity of all the materials tested. Of the three resin-modified glass
      ionomer materials tested, Fuji II LC was the most radiopaque and Photac-Fil the
      least. For the radiopacity of restorative glass-ionomer materials to exceed that
      of enamel, it should be greater than 1.5 mm of equivalent thickness of aluminum.

PMID- 9180423
TI  - We must continue to work hard for unity regarding educational preparation.

PMID- 9180424
TI  - National report: state of the association.
AB  - ANNA has talked the talk and walked the walk of advancing the professional
      development of registered nurses practicing in nephrology, transplantation, and
      related therapies. The list of volunteers that need to be thanked for their time
      and contributions would cover several journal pages. You all know who you are
      because in reading the list of of accomplishments you sense the satisfaction of
      knowing that you you did your part to move ANNA forward. The 1996-1997 year has
      been a good one because you cared, worked, and shared, and for that the Board of
      Directors is forever grateful.

PMID- 9180425
TI  - ANNA (American Nephrology Nurses' Association) position statements.

PMID- 9180426
TI  - Physical assessment of children ages 1 to 10 years.
AB  - This is a two-part article on physical assessment of children with renal
      diseases. The first part of this article deals with the normal physical findings
      in children, ages 1 to 10 years. The article explores the four basic techniques
      of inspection, percussion, palpation, and auscultation according to body systems.
      The second part of this article discusses the physical findings that may be seen
      in children with renal diseases. The physical findings are reviewed according to
      body systems.

PMID- 9180427
TI  - Physical assessment of children ages 1 to 10 years with renal disease.
AB  - This article is a review of the many physical findings that one may encounter
      when examining a child with renal disease. It is the intention of this article to
      increase the knowledge base of the novice and heighten the awareness of advanced
      practitioners in relation to findings specific to infants and children.

PMID- 9180428
TI  - Nutritional management of patients with acute renal failure.
AB  - Patients with acute renal failure are at high risk for developing malnutrition.
      Provision of adequate nutrition support begins with an understanding of the
      metabolic alterations that occur due to the disease state and renal replacement
      therapies. Assessment of nutritional requirements and implementation of
      appropriate feeding modalities can lead to optimal nutritional status and
      positive patient outcomes. Building collaborative relationships with other health
      care professionals is crucial to overcoming the barriers that hinder
      implementation of appropriate nutritional management.

PMID- 9180429
TI  - Creating caring organization cultures in dialysis units.
AB  - Organization culture refers to the ways in which work groups have evolved to
      consider and address issues that face them. In this article, the concept of a
      caring organization culture is described. Elements to consider in creating a
      caring organization culture include: values of the group, qualities of a caring
      leader, management style, decision-making processes, planning for the change,
      taking action, and reflection/evaluation/accountability. Although change to
      organization culture is difficult, it is possible if there is a commitment to the
      change.

PMID- 9180430
TI  - CQI and anemia management: maximizing positive outcomes. Case study of the anemic
      patient.
AB  - Quality improvement techniques provide a scientific approach that allows nurses
      and other health care professionals to improve patient satisfaction and outcomes.
      Continuous quality improvement (CQI) encourages the health care team to move
      beyond minimum standards of care and create an environment in which all team
      members are continuously working to improve services. This article reviews the
      principles of CQI and discusses the nurses' role in implementing and maintaining
      a successful CQI program. Anemia management is used as an example to illustrate
      how CQI principles and tools can lead to improvements in patient outcomes.

PMID- 9180431
TI  - Iron management in ESRD and the role of the nephrology nurse.
AB  - Iron deficiency is common in patients with end stage renal disease (ESRD)
      receiving recombinant human erythropoietin (rHuEPO). Consequently, such patients
      require routine iron monitoring by measurement of serum ferritin and transferrin
      saturation, with interpretation of these values in light of the response to
      rHuEPO. This article will review issues related to iron metabolism, the causes
      and diagnosis of absolute and functional iron deficiency, and treatment options
      for iron deficiency. In addition, the role of the nurse in iron management will
      be identified.

PMID- 9180432
TI  - The value of IDPN as a supplemental therapy when elderly patients fail to thrive-
      two case studies.
AB  - On the last day of his life, H.J. came into the dialysis unit smiling and joking.
      He spent the time watching a movie and visiting with visitors and staff. He
      reported feeling better than he had in a long time. His predicted 3-day death
      watch had become nearly 5 months of improved quality of life and precious time
      spent with his large extended family. He frequently expressed gratitude for the
      chance to prolong those few days into such an unexpected extension. He and his
      family attributed this gift to the nursing care and encouragement he received in
      the dialysis unit. Everyone was aware that the IDPN therapy, along with
      improvement in his own daily nutritional intake, was a critical element. Later
      that night, H.J. had a cardiac arrest, and he died peacefully at home with his
      family. There is no doubt that without the financial resources available to him
      to pay for his IDPN, the outcome would not have been the same. As it was, all the
      intended patient outcomes were achieved.

PMID- 9180433
TI  - Obtaining accurate PTH readings.

PMID- 9180434
TI  - Use of patient care technicians in today's practice environment.

PMID- 9180435
TI  - Multiple center listing for cadaveric donor kidneys: pro and con.

PMID- 9180436
TI  - Leadership.

PMID- 9180437
TI  - Why don't CACCN Inc. members ask for money?

PMID- 9180438
TI  - Assessment of the agreement between cardiac output measured by bolus
      thermodilution and continuous methods, with particular reference to the effect of
      heart rhythm.
AB  - Cardiac output (CO) is a fundamentally important haemodynamic parameter and its
      continuous measurement has the potential to enable early recognition of
      haemodynamic trends and earlier therapeutic response. A method of continuous
      cardiac output (CCO) monitoring is now available for clinical use. The accuracy
      and reliability of this method has been confirmed in clinical trials but not, to
      our knowledge, in the presence of abnormal heart rhythms. A comparison was made
      between CCO and bolus thermodilution methods, to determine if there is a greater
      difference between their respective determinations of CO when heart rhythm is
      abnormal. A convenience sample of 38 intensive care patients was used to obtain
      410 comparisons of CCO and bolus CO determinations. Heart rhythm associated with
      each comparison was determined. The comparison produced a measurement bias of 
      0.07 l/min and limits of agreement of -1.77 to 1.63 l/min. The bias of the two
      measurements was -0.35 l/min for sinus rhythm, -0.19 l/min for sinus tachycardia
      and -0.12 l/min for atrial flutter/fibrillation. Increased temperature and heart
      rate did not affect measurement agreement. In conclusion, the agreement between
      the bolus and continuous methods is clinically acceptable and is unaffected by
      the heart rhythms of sinus rhythm, sinus tachycardia and atrial
      flutter/fibrillation.

PMID- 9180439
TI  - Neonatal nurses' views on the barriers to parenting in the intensive care nursery
      -a pilot study.
AB  - A descriptive study, using a self-reporting questionnaire, was undertaken to
      identify neonatal nurses' views on barriers to parenting in the intensive care
      nursery. The objective of the study was to determine nurses' responses to the
      barriers to parenting identified in the nursing literature. Relevant literature
      was examined and the questionnaire developed. To determine reliability and
      validity, the questionnaire was examined by both medical and nursing experts and
      a pilot study was undertaken, with relevant changes made, as many answers reflect
      current unit policy rather than opinion. Questionnaires were distributed in an
      intensive care nursery in Brisbane, Australia; the nurses were asked to rate the
      extent of their agreement with the points identified in the literature on a seven
      point scale, with 1 being the lowest score and 7 the highest. Of the 80
      questionnaires distributed, 40 were returned. The results of the questionnaire
      indicated an understanding of the environmental and emotional barriers
      confronting parents. However, there was little acknowledgement of the nurse
      initiated practices which also prevent parents fulfilling their parenting role.
      Evenly divided responses were received to several questions, indicating
      inconsistency in neonatal nurses' views on what constitute barriers to parenting.
      The results of the questionnaire are of value in extending neonatal nursing
      knowledge. They provide a snapshot of neonatal nurses' views on the barriers
      confronting parents as they attempt to fulfill their parenting role, and bring
      nurse-initiated barriers, such as policy and procedures, to the attention of
      neonatal intensive care nurses.

PMID- 9180440
TI  - New nursing opportunities in the top end.

PMID- 9180441
TI  - Nurse academics' scholarly productivity: framed by the system, facilitated by
      mentoring.
AB  - The scholarly productivity of 65% of the 1,107 nurse academics employed full-time
      in Australian faculties of nursing and health sciences was investigated by means
      of a survey. This report describes respondents' demographic profile, the
      categories of their publications, their scholarship index ratings and the factors
      that framed (i.e. constrained) and facilitated their efforts to publish their
      work. The study found that overall the academics had a low level of scholarly
      productivity and that the scholarship of three quarters of those who had
      published in the year prior to the survey was not rated highly according to the
      university value system. Respondents' opportunities to publish were framed by job
      factors such as teaching commitments and the need to improve their academic
      qualifications and they were facilitated by mentoring, professional development
      leave and participating in research. The implications of the study are that there
      is an urgent need for nursing mentorship programs, increased access to
      professional development leave and encouragement to undertake research, the
      facilitators of the scholarly productivity which is the foundation of the
      discipline's body of knowledge.

PMID- 9180442
TI  - Critical care nurses' perceptions of their educational needs.
AB  - A survey of nurses working in critical care units in 89 Queensland hospitals was
      conducted to investigate their perceptions of critical care nurses' educational
      needs. Two thirds of the 62 respondents were from rural units and one third were
      from metropolitan units. Most respondents, irrespective of geographic location,
      wanted critical care education to be located in hospitals and to be accredited as
      a graduate diploma course. Rural and metropolitan nurses had similar educational
      needs and many worked for hospitals that were not offering adequate orientation
      or inservice critical care education. The findings that nursing staff turnover
      was a problem in metropolitan units and that the rural workforce was more stable
      have implications for the development of educational programs.

PMID- 9180443
TI  - Expanding the nursing repertoire: the effect of massage on post-operative pain.
AB  - An equivalent groups design with a treatment group of 19 patients and a control
      group of 20 patients was used to investigate the impact of massage therapy on
      patients' perceptions of post-operative pain. Data were analysed using analysis
      of covariance repeated measures (within subjects) design. Controlling for age,
      the results indicated that massage produced a significant reduction in patients'
      perceptions of pain over a 24 hour period. A linear positive relationship emerged
      between patients' age and the duration of the massage. The study indicates that
      further investigation of the potential for massage to reduce pain is warranted.

PMID- 9180445
TI  - The use of physical restraints in Western Australian nursing homes.
AB  - Sixtyfour directors of nursing of Western Australia's 95 nursing homes that
      provide care for elderly residents responded to a survey designed to obtain
      descriptive information about the use of physical restraints. The study found
      that physical restraints had been applied to 26% (n = 787) of the 3028 nursing
      home residents. The most common forms of restraint were bedrails, which were used
      in 38.3% of homes, restraining belts (26.7%) and vests (16.7%). Ninetyfive
      percent of DONs cited "preventing falls" as a patient-oriented reason for using
      physical restraints and 19% said "because no alternative exists" was the nursing
      oriented reason for restraint. While there may have been therapeutic reasons for
      using physical restraints, the extent to which they were used is cause for
      concern. Further efforts to reduce the use of restraints are needed. In
      particular, all nursing home staff involved in direct care of residents should be
      educated about the effects of applying physical restraints and about alternative
      way to manage elderly residents.

PMID- 9180444
TI  - The effect of nursing education and experience on attitudes to diabetes.
AB  - The diabetes-related attitudes of 629 nurses working in South Australian
      hospitals were identified in a study using a questionnaire that included the
      revised Diabetes Attitudes Scale. Overall, the nurses' attitudes were
      appropriate; some were found to be related to levels of nursing education and
      others to nursing experience. There were significant differences between some
      attitudes held by nurses and previously reported attitudes of pre-registration
      nursing students. This study indicates that formal nursing education affects
      nurses' attitudes to diabetes and implications of the findings for inservice
      diabetes programs are discussed.

PMID- 9180446
TI  - The subject of caring.
AB  - Gordon Mitchell argues that the observational skills of nurses are an important
      tool in helping to identify when a patient admitted with depression is, in fact,
      suffering from a medical condition.

PMID- 9180447
TI  - Depression in elderly people.
AB  - Elizabeth Murray describes a new flexible learning programme currently being
      piloted in Nottingham. Its open and distance learning approach makes it
      accessible to a variety of those involved in caring for elderly people.

PMID- 9180449
TI  - Healing cavity wounds with negative pressure.

PMID- 9180448
TI  - Doing the right thing right.
AB  - Is clinical effectiveness just a fancy way of getting nurses to do more with
      less? No, argues Professor Alison Kitson in a discussion on the issues and
      challenges clinical effectiveness presents for nurses and nursing.

PMID- 9180451
TI  - Phantom visions: real enough to touch.
AB  - Blind and partially sighted people are in danger of being wrongly treated for
      mental health problems. Jane Hart explains the phenomenon known as Charles Bonnet
      Syndrome.

PMID- 9180452
TI  - Aromatic mixer.

PMID- 9180453
TI  - Essentials in care.

PMID- 9180454
TI  - Focus on ageism.

PMID- 9180455
TI  - Back to the future.

PMID- 9180456
TI  - Recognition agreements.

PMID- 9180457
TI  - New legal framework in residential care.

PMID- 9180458
TI  - Nursing support for carers.

PMID- 9180459
TI  - Assessment of older people with mental health needs.

PMID- 9180460
TI  - Continence products: a national resource.

PMID- 9180463
TI  - Concern over memory drugs.

PMID- 9180462
TI  - Tuberculosis.

PMID- 9180461
TI  - Health and social care in the community.

PMID- 9180464
TI  - The road to hell....

PMID- 9180465
TI  - Lives in context.

PMID- 9180466
TI  - Effective care for vulnerable people.

PMID- 9180468
TI  - TV debate is a dog's breakfast.

PMID- 9180467
TI  - A change of FOCUS.

PMID- 9180470
TI  - An innovative night service program in home care.
AB  - Comprehensive night service by a home care agency has resulted in increased
      customer satisfaction and referrals to the agency. The description of this
      innovative night nurse program includes the job requirements and duties of a
      visiting night nurse and the tools the nurse uses to accomplish the task of
      nighttime care delivery. The use of self-directed work groups and mentorship to
      manage the demands of night service are discussed. Continuity of care, nurse
      safety, professional development, and program cost also are addressed.

PMID- 9180469
TI  - Cryptosporidium.

PMID- 9180471
TI  - The medical social worker: member of the home healthcare team.

PMID- 9180473
TI  - Frequently asked questions about OASIS: answers from a rural agency participant.

PMID- 9180474
TI  - Implementing clinical pathways: one agency's experience.
AB  - The shift to managed care is forcing home health agencies to evaluate their
      methods of service delivery and documentation. Managed-care organizations are
      demanding that agencies demonstrate that they can provide cost-effective, quality
      services within a specified period. The outcomes of care, per visit or per
      admission, represent the indicators of whether these demands are being met. Many
      home health agencies are turning to clinical pathways to delineate their services
      and strengthen their documentation. This article provides a description of one
      agency's experience in implementing clinical pathways.

PMID- 9180475
TI  - Primary prevention of falls.

PMID- 9180472
TI  - Consultation with physical and occupational therapists to promote the motor
      development of young children.
AB  - Increased survival of infants with complex medical needs combined with fiscal
      constraints have resulted in more young children receiving home care nursing.
      Home care nurses can enhance their role by understanding how physical and
      occupational therapists provide consultation to the family and nursing staff.

PMID- 9180476
TI  - Chemotherapy in the workplace.

PMID- 9180477
TI  - Amber E. Nichols. Interview by Christopher Wood.

PMID- 9180478
TI  - Marching for global change.

PMID- 9180479
TI  - A student experiences Managua, Nicaragua.

PMID- 9180480
TI  - Adventure in Oaxaca.

PMID- 9180481
TI  - A profile of the International Nursing Center at the American Nurses Foundation.

PMID- 9180482
TI  - Helping children adjust to life with an ill sibling.

PMID- 9180484
TI  - Facing today's job market.

PMID- 9180483
TI  - Don't forget about caring.

PMID- 9180485
TI  - Graduate education in nursing: an update.

PMID- 9180486
TI  - So you've graduated ... now what? Student perspectives.

PMID- 9180487
TI  - The new graduate nurse preceptor program an overview.

PMID- 9180488
TI  - Questions and answers about the NCLEX.

PMID- 9180489
TI  - Third place essay contest winner. The nurse I admire most.

PMID- 9180490
TI  - Controlling and using the power of the information explosion.

PMID- 9180491
TI  - Exploring dichotomies of caring, gender and technology in intensive care nursing:
      a qualitative approach.
AB  - Intensive care nursing involves combining caring, seen as a feminine trait, with
      the ability to work with technology, often viewed as masculine. This study
      explored nurses perceptions of their work, particularly in relation to whether
      there are differences between the sexes in caring ability and the planned career
      paths of female and male nurses. It was also designed to investigate the
      attractions of intensive care nursing and what nurses disliked most about their
      jobs. The results challenge previous studies which state that male nurses are
      attracted to these areas because of the technology and that they wish to climb
      the career ladder more quickly than their female colleagues. Nurses in intensive
      care units generally chose such work because they were able to provide, in their
      own opinions, a high standard of nursing care to patients and were able to
      maintain direct patient contact if they wished to achieve sister/charge nurse
      posts.

PMID- 9180492
TI  - Microbial colonization of closed-system suction catheters used in liver
      transplant patients.
AB  - The microbial colonization and the associated risk of respiratory infection
      during the application of a multiple-use closed-system suction catheter (CSSC)
      and a single-use open-system suction catheter (OSSC) on liver transplant patients
      was evaluated in this preliminary study. The cost differential for the two
      systems was also compared. Twenty post-orthotopic liver transplant (OLTx)
      patients who were mechanically ventilated via an endotracheal (ET) tube were
      studied. Ten subjects were randomly allocated ET suction by the CSSC and 10 with
      OSSC. Both groups were similar according to age, sex, clinical severity, presence
      of a naso-gastric tube, use of H2 antagonists and antibiotics used. Standard
      protocols were followed to intubate and suction the patients and to change
      ventilatory equipment. Suctioning performed with the CSSC did not significantly
      increase the risk of microbial colonization of the respiratory tract. Similarly
      there was no apparent difference in the incidence of nosocomial pneumonia between
      the two suction systems, based on the microbiological and clinical data. The mean
      daily cost of using the CSSC compared to the OSSC was 11.6 times higher. This may
      be balanced by a reduction in nursing time and reduced risk of spread of
      infection associated with the CSSC.

PMID- 9180493
TI  - Nurse-initiated extubation following cardiac surgery.
AB  - Early extubation is now advocated for most patients after cardiac surgery. This
      article contains an examination of changes in extubation practice and addresses
      the development and implementation of a protocol for nurse-led extubation for
      this patient group. The knowledge and experience required by nurses to undertake
      this role is discussed and suggestions for auditing this aspect of nursing care
      explained.

PMID- 9180494
TI  - Advanced practitioners: the hidden agenda?
AB  - Changes in health-care provision and the increased expectations of clients have
      precipitated major developments throughout the service. The trend towards
      specialist and advanced practitioners has been embraced by nurses as the route to
      professional recognition and increased status. The focus of this paper is
      consideration of the factors influencing these developments, observing the
      concurrent erosion of nursing values and strength. Health service management, ill
      informed of nurses' function within the service, conclude that task distribution
      will be cost-effective. To this end, health-care assistants with National
      Vocational Qualifications (NVQs) performing nursing duties and nurses undertaking
      junior doctors' work, thereby reducing their hours, have been actively
      encouraged. Nurses, preoccupied with continuing debates surrounding new titles
      and improving status through the acquisition of medico-technical skills, have
      failed to consider the effects of advancing practice without first affirming
      their own unique identity. Nurses should appreciate the increasing risk to their
      own profession caused by lack of clarity and apparent compliance, which
      contribute to the management view of nurses as doctors' assistants--or
      handmaidens.

PMID- 9180495
TI  - Nitric oxide: some nursing implications.

PMID- 9180496
TI  - Have nursing models a place in intensive care units?
AB  - The usefulness of conceptual models to guide nursing practice within an intensive
      care unit is explored within this paper. In order to do this, the term 'nursing
      model' is first of all defined and the three key types identified. The benefits
      and difficulties of utilizing a nursing model are then considered. Within this
      discussion, the relationship of the nursing process to a nursing model is
      highlighted, as is the opportunity to give a structured and scientific base to
      clinical practice. Potential problems relating to the language used within the
      model are acknowledge. Finally, the selection and use of models within this area
      of practice is explored.

PMID- 9180497
TI  - Setting up a paediatric retrieval team.
AB  - In this article some aspects to be considered when setting up a paediatric
      retrieval service are examined. These include equipment problems to be overcome,
      selection and training of staff, and communication issues. For the purposes of
      the article the words 'retrieval', 'transfer', and 'transport' teams, are used
      interchangeably for the same meaning.

PMID- 9180498
TI  - Withdrawing treatment from a critically-ill child.
AB  - In this paper the ethical and legal implications of withdrawing treatment from a
      critically-ill child are examined. Paediatric nurses in intensive care units
      often rely on intuition for resolving emotive issues such as the withdrawal of
      treatment from a child. To enhance their contribution in the decision-making
      process nurses need knowledge of ethical theories and principles, and the law.
      Advances in technology, together with political and economic factors, could well
      result in more attention being placed on ethical and legal issues in paediatric
      intensive care units. For the purpose of this paper pseudonyms have been used.

PMID- 9180499
TI  - Principles and practice of managing difficult behaviour situations in intensive
      care.
AB  - Nurses working in intensive care units may be vulnerable to verbal or physical
      aggression from relatives. This article explores the principles and skills
      associated with de-escalating aggression in such scenarios. These nurses may also
      be exposed to manipulative patterns of behaviour on the part of relatives and the
      article explores a research technique with which to manage this kind of
      situation.

PMID- 9180500
TI  - Meeting the informational, psychosocial and emotional needs of each ICU patient
      and family.
AB  - The acquisition of counselling skills and a review of current practice within a
      cardiothoracic intensive care unit (ICU) have revealed the need for a nursing
      development that will focus on meeting the informational, psychosocial and
      emotional needs of patients and their families. The findings from a literature
      search suggest that these needs are not always adequately met. Difficulties may
      be encountered by patients and their families whilst trying to adjust to a stay
      in the ICU, to transfer to the ward, and following discharge home. Providing a
      client-driven service that effectively meets these complex needs could be
      achieved by developing a specialist role in intensive care nursing. The patients
      and their families could be offered provision of information and supportive
      strategies that extend from admission to the ICU, through transfer to a ward, and
      beyond. The aim of the service would be to provide patient- and family-centred
      continuity of care throughout the acute and rehabilitative stages of the crisis
      (Turner 1992). The utilization of counselling skills could help to facilitate the
      service, and help each client to feel supported (Tschudin 1995, p 33).

PMID- 9180501
TI  - Docetaxel (taxotere, Rhone-Poulenc Rorer).
AB  - Docetaxel is the latest in a new class of cytotoxic drug having a specific action
      on dividing cells. It is potentially a useful, if expensive, treatment for some
      common cancers in which the response to existing treatments has been generally
      disappointing.

PMID- 9180502
TI  - Eradication therapy in peptic ulcer disease.

PMID- 9180503
TI  - The complexity of basic care.

PMID- 9180504
TI  - The history of the bath: from art to task? Reflections for the future.

PMID- 9180505
TI  - Reducing aggressive behavior during bathing cognitively impaired nursing home
      residents.

PMID- 9180506
TI  - Physical aggressive resident behavior during hygienic care.
AB  - Management of aggressive behavior has been identified as a concern for nursing
      staff who provide institutional care for cognitively impaired elderly. The
      Omnibus Reconciliation Act (OBRA '87) mandates a trial reduction in the use of
      chemical and physical restraints, and the development of nursing interventions
      for the management of behavioral disorders of institutionalized cognitively
      impaired elderly. Most skilled nursing facilities, however, are limited in their
      ability to provide environmental and behavioral programs to manage aggressive
      patient behavior. For the purposes of this study, physically aggressive behavior
      was identified as threatened or actual aggressive patient contact which has taken
      place between a patient and a member of the nursing staff. This study explored
      the nursing staff's responses to patient physical aggression and the effects that
      physical aggression had on them and on nursing practice from the perspective of
      the nursing staff. Nursing staff employed on one Dementia Special Care Unit
      (DSCU) were invited to participate. Interviews with nursing staff were analyzed
      using qualitative descriptive methods described by Miles and Huberman (1994).
      Nursing staff reported that they were subjected to aggressive patient behaviors
      ranging from verbal threats to actual physical violence. Nursing staff reported
      that showering a resident was the activity of daily living most likely to provoke
      patient to staff physical aggression. The findings revealed geropsychiatric
      nursing practices for the management of physically aggressive residents, and
      offered recommendations for improving the safety of nursing staff and residents
      on a secured DSCU.

PMID- 9180507
TI  - International perspectives on bathing.

PMID- 9180508
TI  - Bathing: it's a tough job!

PMID- 9180509
TI  - Designing the environment to make bathing pleasant in nursing homes.

PMID- 9180510
TI  - Narratives on pain and comfort: Mary's story.

PMID- 9180511
TI  - Narratives on pain and comfort: Dr. M's story.

PMID- 9180512
TI  - Narratives on pain and comfort: Casey's story.

PMID- 9180513
TI  - Narratives on pain and comfort: readings from Endings and Beginnings.

PMID- 9180514
TI  - Opioid therapy for chronic nonmalignant pain: clinician's perspective.

PMID- 9180515
TI  - Controlled substances and pain management: regulatory oversight, formularies, and
      cost decisions.

PMID- 9180516
TI  - The Pain Relief Act. Project on legal constraints on access to effective pain
      relief.

PMID- 9180517
TI  - Disciplinary actions and pain relief: analysis of the Pain Relief Act.

PMID- 9180518
TI  - Pain management: Texas legislative and regulatory update.

PMID- 9180519
TI  - Pain management and disciplinary action: how medical boards can remove barriers
      to effective treatment.

PMID- 9180520
TI  - Improving pain management through policy making and education for medical
      regulators.

PMID- 9180521
TI  - Pain: ethics, culture, and informed consent to relief.

PMID- 9180522
TI  - Health care providers' liability exposure for inappropriate pain management.

PMID- 9180523
TI  - The role of hospice philosophy of care in nonhospice settings.

PMID- 9180524
TI  - Christian perspectives on assisted suicide and euthanasia: the Anglican
      tradition.

PMID- 9180525
TI  - Health Insurance Portability and Accountability Act of 1996: a tempered victory.

PMID- 9180526
TI  - Conflicting interpretations of Anti-Kickback statute open door to Supreme Court
      review.

PMID- 9180527
TI  - Supreme Court protects communications in psychotherapy.

PMID- 9180528
TI  - Fifth Circuit holds ERISA preempts Louisiana's any willing provider statute.

PMID- 9180529
TI  - Court limits board of medicine's ability to discipline.

PMID- 9180530
TI  - New Jersey Superior Court broadens physician's duty to warn.

PMID- 9180531
TI  - The first ever qualified nurses elected to the House of Commons.

PMID- 9180532
TI  - Jubilation as first nurses elected to parliament.

PMID- 9180533
TI  - Lifting the lid on back injury myths.

PMID- 9180534
TI  - Thanks, but no thanks.

PMID- 9180535
TI  - Facing the music.

PMID- 9180536
TI  - Safe conduct.

PMID- 9180537
TI  - The new guidelines.

PMID- 9180538
TI  - Spying at work.

PMID- 9180539
TI  - Two-in-one vaccine.

PMID- 9180540
TI  - Protection of nurses working with children.

PMID- 9180541
TI  - Health visitor support for patients with breast cancer--1.
AB  - In the first two articles, the author reports on research exploring the attitudes
      towards, and knowledge and experience of, caring for patients with breast cancer
      of health visitors (HVs) acting as resource personnel for colleagues. The study
      also examined how they used their knowledge and what difference it made to
      patients' coping ability at various stages of the disease. The HVs underwent a
      short education programme to increase their ability to help patients in several
      key ares. All the HVs described the support of patients with treated breast
      cancer in the community as important. While they felt that their support to
      patients was mainly psychological, they also described giving medical information
      and assisting with a number of social problems. HVs were constrained by their
      existing caseloads in the time they could give to patients with breast cancer.
      However, the research showed that only a minority of patients required more
      intensive support, most being satisfied with one visit and the opportunity of
      further contact should this be necessary. The second article will appear in two
      weeks.

PMID- 9180542
TI  - Enteral feeding for the critically ill patient.
AB  - This article challenges nurses to examine their practice and procedure when
      establishing enteral feeding. The author suggests that discontinuation for
      'complications' such as diarrhoea may not be appropriate, and recommends that
      nurses take more responsibility for patient nutrition.

PMID- 9180543
TI  - Accreditation of prior experimental learning.
AB  - Accreditation of prior experimental learning (AP(E)L) has gained momentum as a
      way of achieving academic credit. This article outlines the steps to be taken
      when making an AP(E)L claim.

PMID- 9180544
TI  - Implementing research findings in practice.

PMID- 9180545
TI  - The UKCC's tougher approach towards nurses who are convicted sexual offenders.

PMID- 9180546
TI  - Removed from the register.

PMID- 9180547
TI  - Time to toughen up?

PMID- 9180548
TI  - Frank speaker with a healthy interest.

PMID- 9180549
TI  - No strings attached.

PMID- 9180550
TI  - A chance to change society.

PMID- 9180551
TI  - The future of nurse education.

PMID- 9180552
TI  - Mapping the future.

PMID- 9180553
TI  - Ancient and modern.

PMID- 9180555
TI  - Nursing and public health: the future.

PMID- 9180554
TI  - Universal precautions.

PMID- 9180556
TI  - Auditing a clinical supervision training programme.
AB  - Nurses and service managers in a community trust were asked to evaluate a
      training course designed to help them implement the trust's clinical supervision
      policy. The audit identified several patterns of clinical supervision emerging
      within the trust. The author discusses the benefits of these to patients, staff
      and the organisation and draws some recommendations for nurses involved in
      implementing clinical supervision.

PMID- 9180557
TI  - Intensive care for people with serious mental illness.
AB  - This article describes the development of a psychiatric 'intensive care' service
      for men and women with serious or enduring forms of psychotic disorder. The
      authors suggest that such a residential therapeutic service may be an essential
      part of the development of community care for the most vulnerable people served
      by mental health services.

PMID- 9180558
TI  - Clinical effectiveness.

PMID- 9180560
TI  - UK introduces new resuscitation guidelines.

PMID- 9180559
TI  - What happens beyond Project 2000 is the big question in nurse education.

PMID- 9180561
TI  - Recruitment and redundancies.

PMID- 9180562
TI  - Experience that counts.

PMID- 9180563
TI  - Open doors.

PMID- 9180564
TI  - New patterns suit nurses.

PMID- 9180565
TI  - Keep on changing.

PMID- 9180566
TI  - Strike lucky.

PMID- 9180567
TI  - Election survey.

PMID- 9180568
TI  - Pushing for policies.

PMID- 9180569
TI  - Victims of suspicion.

PMID- 9180570
TI  - Equal at last.

PMID- 9180571
TI  - Caring for older people in the community.
AB  - This is a brief report of the aims and structure of a two-year project, which
      commenced in August 1996, researching the educational needs of nurses who care
      for older people in the community. The study involves the development and
      evaluation of an educational programme designed to help improve the efficiency of
      nurses working in this area.

PMID- 9180573
TI  - The rhythms of life: chronobiology and nursing.
AB  - Understanding chronobiology--the study of biological rhythms--can help nurses
      care for their patients and themselves. This article discusses the internal and
      external factors which affect the body's daily rhythms, and the effectiveness of
      different drugs and procedures at certain times of the day. The author also
      offers advice for nurses anticipating night work to minimise disruption to their
      own circadian rhythm.

PMID- 9180572
TI  - Managers' attitudes towards mechanical aids.
AB  - This article reports a study of the attitudes of NHS management and financial
      personnel to issues of moving and handling, in particular the use of mechanical
      aids. The study highlights some confusions about the responsibilities and roles
      of different personnel, and the authors make some recommendations to clarify
      these.

PMID- 9180574
TI  - Applying empowerment in mental health practice.
AB  - The concept of empowerment has been widely discussed and its psychological and
      political meaning explored. However, it is rarely described in the context of
      nursing practice. This article focuses on the practice of empowering individuals
      with learning difficulties, within a secure setting. The ideas may be applied to
      any healthcare setting.

PMID- 9180575
TI  - The menopause and hormone replacement therapy.

PMID- 9180577
TI  - The Government Relations Committee hosts a workshop with a purpose.

PMID- 9180576
TI  - 20 years: a celebration of achievement and a look to the future.

PMID- 9180579
TI  - Update: priority issues in communication disorders.

PMID- 9180578
TI  - Aiming toward tobacco free youth: progress on anti-tobacco efforts.

PMID- 9180580
TI  - Grassroots participation on your own turf: developing a personal political action
      plan.

PMID- 9180581
TI  - Review of tracheostomy videos for staff education.
AB  - Tracheostomy care is a basic nursing skill. While it is a matter of routine
      procedure in the daily practice of otolaryngology and critical care nurses,
      general nurses in other areas may perform it infrequently. Therefore, many
      otolaryngology nurses provide staff education when a tracheostomy patient is
      present in a nonspecialty area. This educational effort can be time consuming and
      repetitious for the specialty nurse. Audiovisual materials can be useful as a
      basis for an educational session or as a substitute when the specialty nurse is
      unavailable. The author conducted a thorough search for available videorecordings
      on nursing care of adults with tracheostomies. Four videos were identified and
      acquired. Each one was viewed twice, and then subjectively rated for completeness
      and accuracy of content in a comparative, "Consumer Reports"-like manner.
      Recommendations are made considering content, cost, and availability. The review
      is written for experienced clinicians and presumes a thorough knowledge of
      tracheostomy care.

PMID- 9180582
TI  - SMR machines.

PMID- 9180583
TI  - Coping with disfigurement/dysfunction and length of hospital stay after head and
      neck cancer surgery.
AB  - The purpose of this study is to determine if an individual's use of coping
      strategies prior to sustaining facial disfigurement/dysfunction is predictive of
      coping effectiveness after head and neck cancer surgery. The specific aims of the
      study are as follows: (1) describe the relationship between demographic data,
      preoperative coping strategies, severity of disfigurement/dysfunction,
      postoperative healing progress, and length of postoperative hospital stay; (2)
      describe the relationship between demographic data, preoperative coping
      strategies, and postoperative coping behaviors; (3) determine the relationship
      between postoperative coping behaviors and length of hospital stay. The Stress
      Coping Model of Scott, Oberst and Dropkin (1980) provides the theoretical
      framework for this study. The sample consisted of 117 adults who were about to
      undergo head and neck cancer surgery associated with disfigurement/dysfunction.
      Zero-order correlations were computed among the variables, including preoperative
      use of coping strategies, degree of postoperative disfigurement/dysfunction,
      postoperative coping behaviors, postoperative complications, and length of
      hospital stay. Multiple regression analyses were conducted on the major outcome
      variables: length of stay and postoperative coping behaviors. Gender (female),
      preoperative radiation therapy, preoperative chemotherapy and postoperative
      problems were found to significantly increase length of stay. The 16 predictors
      in this study contributed to 56% of the variance in length of stay. Fifteen
      predictors accounted for 25% of the variance in postoperative coping.

PMID- 9180584
TI  - Nursing interventions for potential complications after thyroidectomy.

PMID- 9180585
TI  - 1996 NOLF meeting.

PMID- 9180586
TI  - Problem in tracheostomy patient care: recognizing the patient with a displaced
      tracheostomy tube.
AB  - There are times when a tracheostomy tube slips out of the trachea. A displaced
      tracheostomy tube can occur in any patient but is frequently seen in the patient
      with a full neck. In the overweight patient or patient with a full neck, the
      tracheostomy tube must pass through a greater amount of soft tissue. Because of
      this, a smaller portion of the tube is actually within the lumen of the trachea.
      When the patient coughs excessively or moves the head, the tube can easily slip
      out of the trachea and into the interstitial tissues of the neck. If the patient
      has complete obstruction of the upper airway, a displaced tracheostomy tube will
      result in immediate respiratory distress and can lead to respiratory arrest. If
      the patient has an intact or at least a partially open upper airway, the
      displaced tube may not cause an immediate problem. Therefore, displacement of the
      tracheostomy tube may not be obvious in the patient with a partial airway.

PMID- 9180587
TI  - Nurse in Washington Internship (NIWI).

PMID- 9180588
TI  - Nursing management of office-based surgical procedures.
AB  - This paper outlines nursing management of the patient undergoing an office- or
      clinic-based surgical procedure. It identifies key nursing responsibilities in
      caring for a patient receiving conscious sedation as well as providing examples
      of pre- and post procedure instructions, and documentation guidelines currently
      in use in the Otolaryngology/Head and Neck Surgery Clinic at University of North
      Carolina (UNC) Hospitals, as well as pictures of a typical otolaryngology
      procedure and recovery room.

PMID- 9180589
TI  - Endoscopic sinus surgery in otorhinolaryngology nursing using powered
      instrumentation.
AB  - Powered instrumentation has gained increased popularity in otolaryngology because
      of its safety and effectiveness in sinus surgery. An understanding of the
      principles and techniques of powered dissection of the sinuses, setup and
      handling of instrumentation, and pre- and postoperative care is necessary for
      otolaryngology nurses in management of patients undergoing these procedures.

PMID- 9180590
TI  - Practical and professional aspects of i.v. therapy.
AB  - The basic principles of good i.v. practice provide a firm foundation for the
      continued expansion of i.v. therapy. Nurses must be aware of the professional
      documents that underpin nursing practice, and how these relate to i.v. therapy.
      Nurses must understand the legal implications of care delivery and ensure they
      have the necessary knowledge to expand their practice safely.

PMID- 9180591
TI  - Principles of intravenous fluid replacement.
AB  - Infusates are used to expand the intravascular volume or to influence solute
      composition of body fluids. The choice of infusate depends on the underlying
      physiological disturbances. A variety of infusates are used and it is important
      that the consequences of over-infusion are understood.

PMID- 9180592
TI  - Intravenous cannulation: potential complications.
AB  - The procedure of establishing peripheral venous access carries the risk of
      potential complications to both the patient and the practitioner. Complications
      include infection, phlebitis and thrombophlebitis, emboli, pain, haematoma or
      haemorrhage, extravasation, arterial cannulation and needlestick injuries.
      Careful adherence to guidelines and procedures can minimise these risks.

PMID- 9180593
TI  - Selection of intravenous infusion pumps.
AB  - Three broad types of intravenous infusion pump are available--gravity driven,
      electronic and mechanical devices. The type suitable for a unit will depend on
      the patient group. Nurses are generally responsible for administering intravenous
      infusions and should therefore be involved in the purchasing process.

PMID- 9180594
TI  - Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi
      antigens in chronic, human, chagasic myocarditis.
AB  - The role of Trypanosoma cruzi in the pathogenesis of myocarditis in the chronic
      phase of Chagas' disease is still controversial, with autoimmune mechanisms
      frequently being proposed. In the present work, we demonstrate that higher
      numbers of CD8+ T cells are correlated with the presence of parasite antigens,
      suggesting an important role for the parasite in the development of myocardial
      inflammation. Quantification of the mean numbers of CD8+ and CD4+ T cells per
      400x microscopic field was performed in myocardial specimens from 33 chronic
      chagasic patients with heart failures (nine biopsies and 24 necropsies), using an
      immunoperoxidase technique. The cases were grouped according to a
      semiquantitative score of the relative amounts of T. cruzi antigens: group 1 =
      absent (14 cases); group 2 = scarce extracellular or intramacrophagic antigens
      (12 cases); group 3 = many extracellular or intramacrophagic antigens plus T.
      cruzi intramyocytic pseudocysts (seven cases). The mean numbers of CD8+ and CD4+
      T cells in groups 1,2, and 3 were 6.94 and 3.79, 13.89 and 6.24, and 17.91 and
      5.97, respectively. The numbers of CD8+ T cells in groups 2 and 3 were
      significantly higher compared with group 1 (no T. cruzi antigens), but were not
      different from each other. Scarce, extramyocytic T. cruzi antigens were
      associated with an intense inflammatory infiltrate, suggesting that delayed-type
      hypersensitivity immune mechanism is induced by the parasite; intact
      myocardiocytes containing parasites did not show an inflammatory reaction around
      them. A poor inflammatory response was frequently associated with many
      extramyocytic antigens and myocardial parasite pseudocysts, suggesting that
      active proliferation and dissemination of the parasites occur when the
      immunologic response is diminished. The number of CD4+ T cells did not vary
      significantly among the three groups. We conclude that the CD8+ T cell is the
      main cell type responsible for immune activation in chronic, human, chagasic
      myocarditis and is probably activated by the presence of T. cruzi antigens
      associated with internal myocytic host antigens. The absence of a significant
      member of CD4+ T cells in the presence of T. cruzi antigens suggests inhibition
      of CD4+ T cell activation or the lack of a class II major histocompatibility
      complex molecule presentation mechanism.

PMID- 9180595
TI  - Comparison of clinical features and pathologic findings in fatal cases of typhoid
      fever during the initial and later stages of the disease.
AB  - This study was undertaken to correlate the clinical features and pathologic
      changes noted during the initial and later stages of fatal typhoid illness. Five
      cases who died during the initial stage of the illness (< 2 weeks from onset) had
      altered mental status, tachypnea, and tachycardia. Three had shock and elevation
      of serum creatinine values. Autopsies of all five revealed hyperplastic Peyer's
      patches, features of adult respiratory distress syndrome, and megakaryocytosis.
      Five other cases died during the later stage of the illness (> or = 2 weeks after
      onset). They had a left shift in peripheral blood leukocyte count. Autopsies
      revealed deep ileal ulcerations with or without perforation and peritonitis and
      intercurrent pneumonia. Three of them had disseminated intravascular coagulation.
      Further studies are warranted to understand the mediators of shock and tissue
      injuries during the initial period of the illness.

PMID- 9180596
TI  - Prolongation of the QTc interval in African children treated for falciparum
      malaria.
AB  - Antimalarial drugs can affect the heart and trigger life-threatening arrhythmias.
      However, little is known about the frequency with which cardiac abnormalities
      occur during uncomplicated attacks of malaria. Therefore, we have studied the
      electrocardiograms of 139 Gambian children with uncomplicated falciparum malaria
      who were treated with co-artemether, pyrimethamine/sulfadoxine, or chloriquine.
      The QTc intervals were measured on presentation, and four and eight days after
      treatment. No significant differences in mean QTc or heart rate were found
      between children in the three treatment groups on days 0, 4, or 8. After
      adjustment for the type of antimalarial thearapy in an analysis of variance, the
      mean (SD) QTc intervals on days 0, 4, and 8 were 402 (22.6), 416 (23.1), and 405
      (24.3) msec, respectively. The mean QTc on day 4 was significantly longer than
      the mean QTc on days 0 or 8 (P < 0.01 in both cases). A quadratic line was fitted
      for QTc against time for each antimalarial therapy. No significant differences
      were found between the quadratic lines of the three groups. A weak association
      was found between QTc and the degree of parasitemia (r = 0.17, P = 0.04) and
      temperature (r = -0.23, P = 0.01) measured on day 0. The QTcs were measured in 18
      children who experienced a second episode of malaria. The changes in QTc observed
      during second episodes were similar to those observed during the first attack.
      Changes in QTc in five children who developed severe malaria were similar to
      those found in the remaining children who did not develop severe malaria. This
      study indicates that the QTc interval changes during the early phase of malaria
      and this change is independent of the type of antimalarial therapy given.

PMID- 9180597
TI  - Disposition of proguanil in Thai patients with uncomplicated falciparum malaria.
AB  - The objective of this study was to examine the disposition of proguanil in
      malaria-infected Thai patients with acute uncomplicated falciparum malaria.
      Eleven patients were administered 500 mg of proguanil twice a day for three days
      (total dose = 3,000 mg). Four patients were tentatively classified as extensive
      metabolizers (EMs) and seven as poor metabolizers (PMs). The mean plasma
      clearances of proguanil for EMs and PMs were 1.31 and 1.10 L/hr/kg, respectively.
      The mean elimination half-life of proguanil was statistically longer in PMs than
      EMs (19.6 hr versus 16.1 hr; P = 0.01). Plasma clearance and elimination half
      life of proguanil in the malaria patients were comparable with those reported in
      the literature for healthy Thai volunteers. In contrast to other ethnic groups.
      Thai EM patients had relatively low plasma concentrations of cycloguanil, the
      active metabolite of proguanil. None of the 11 patients treated with proguanil
      were cured of malaria and their phenotype status did not affect the treatment
      outcome. Although high levels of parasite resistance to cycloguanil were probably
      responsible for the poor response to proguanil treatment, the inability of Thai
      EM and PM patients to produce cycloguanil may have also contributed to the
      treatment outcome.

PMID- 9180598
TI  - The pharmacokinetics of a single dose of artemisinin in patients with
      uncomplicated falciparum malaria.
AB  - The pharmacokinetics of artemisinin was studied in 11 Vietnamese patients with
      uncomplicated falciparum malaria after a single 500 mg oral dose. Curative
      treatment with mefloquine (15 mg/kg) was provided 24 hr after the artemisinin
      dose. Artemisinin concentrations were measured by high-performance liquid
      chromatography with electrochemical detection. The following pharmacokinetic
      results were found (all mean +/- SD); calculated volume of
      distribution/bioavailability = 22.8 +/- 16.6 L.kg-1, mean absorption time = 1.16
      +/- 0.92 hr, calculated maximum concentration = 364 +/- 250 micrograms.L-1
      occurring at 2.88 +/- 1.71 hr after drug intake, and an elimination half-life of
      2.72 +/- 1.76 hr. Bioavailability was low. These results do not differ from
      results in healthy subjects. Parasites disappeared rapidly, with a mean parasite
      clearance time of 36 hr. No relationship was found between pharmacokinetics and
      the parasite elimination rate. Tolerance to the single dose of artemisinin was
      good. No adverse effects were detected. In conclusion, pharmacokinetics of a
      single dose of artemisinin for uncomplicated falciparum malaria is not different
      from findings in healthy subjects. A single dose of 500 mg of artemisinin is
      effective in reducing parasitemia in nonsevere lalciparum malaria and is well
      tolerated.

PMID- 9180599
TI  - WR 238605, chloroquine, and their combinations as blood schizonticides against a
      chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys.
AB  - The compound WR 238605 is a primaquine analog being developed by the U.S. Army as
      an antimalarial drug. Currently, there is no established treatment for Plasmodium
      vivax parasitemias that are not cured by chloroquine. This study tested WR
      238605, chloroquine, and their combinations against a chloroquine-resistant
      strain of P. vivax (AMRU 1) in Aotus monkeys. A total dose of 3 mg/kg of WR
      238605 given at a dosage of 1 mg/kg/day for three days cleared patent parasites
      in all eight monkeys but recrudescence of parasitemia occurred 15-25 days after
      initiation of treatment. A total dose of 9 mg/kg of WR 238605 over a three-day
      period cured all three monkeys of their infections. A total dose of 30 mg/kg of
      chloroquine did not clear patent infections in three monkeys, whereas a total
      dose of 60 mg/kg generally (two of three) cleared patent parasitemia but did not
      cure. Whereas total doses of 30 mg/kg of chloroquine or 3 mg/kg of WR 238605
      given alone failed to cure, both drugs given in combination at these dosages
      cured two of three infections. These results indicate that WR 238605 may be an
      alternative treatment for chloroquine-resistant vivax malaria.

PMID- 9180600
TI  - Therapeutic evaluation of two different dose regimens of praziquantel in a recent
      Schistosoma mansoni focus in Northern Senegal.
AB  - A therapeutic trial, involving 130 Schistosoma mansoni-infected children, with no
      previous history of antischistosomal treatment, was carried out to evaluate the
      efficacy of two different dose regimens of praziquantel. The study was carried
      out because low cure rates were described in this recently established (1990) S.
      mansoni focus in northern Senegal, following treatment with a standard dosage of
      40 mg/kg. The subjects were randomly allocated into two groups: one group (1)
      received 40 mg/kg in one oral dose, the other group (2) was treated with two oral
      doses of 30 mg/kg at a 6-hr interval. Parasitologic examination and circulating
      anodic antigen (CAA) detection were performed before, 10 days, three, six, and 21
      weeks after chemotherapy. No significant differences in cure rates were found
      between the two groups. Six weeks after treatment, 34% and 44% of the individuals
      were found to be stool negative in group 1 and group 2, respectively. However,
      only 10-15% became completely negative according to the serum CAA antigen assay.
      Mean egg counts were reduced by 99% in both groups. Antigen detection confirmed
      the parasitologic results. Fewer side effects were observed in the group treated
      with 2 x 30 mg/kg, which may be explained by split dosage administration. Our
      study shows that the low cure rates observed in this area could not be improved
      by using a higher dosage of praziquantel.

PMID- 9180601
TI  - Studies on schistosomiasis in western Kenya: I. Evidence for immune-facilitated
      excretion of schistosome eggs from patients with Schistosoma mansoni and human
      immunodeficiency virus coinfections.
AB  - Persons employed as vehicle washers in the town of Kisumu, Kenya are exposed for
      several hours each day to water in Lake Victoria that contains Schistosoma
      mansoni-infected Biomphalaria pherifferi snails. This results in a focus of high
      endemicity for schistosomiasis and these persons have very high concentrations of
      eggs in their feces (mean +/- SD = 1,469 +/- 1,581 eggs per gram [EPG] of feces).
      Fecal egg counts, but not circulating cathodic antigen (CCA) levels, in these
      schistosomiasis patients differed strikingly based on the patient's
      seropositivity for human immunodeficiency virus (HIV). Patients who were infected
      with S. mansoni and were seropositive for HIV had similar levels of CCA but
      excreted fewer eggs (643 +/- 622 EPG; n = 16) than individuals who were not
      seropositive for HIV infection (1,891 +/- 1,779 EPG; n = 37) (P = 0.009). Egg
      excretion ratios (EPG/CCA) of the seronegative group were also significantly
      higher than those of the seropositive group. Those in the seropositive group
      showed a significant correlative relationship between egg excretion ratios and
      CD4+ lymphocyte percentages. These observations are compatible with the
      hypothesis that schistosome eggs exit the human host through the requisite
      facilitation of functional immune responses, and that the efficacy of this
      process decreases in schistosomiasis patients co-infected with HIV as their
      peripheral blood CD4- cell levels decrease.

PMID- 9180602
TI  - Circulating T helper 1 (Th1) cell- and Th2 cell-associated cytokines in Indian
      patients with visceral leishmaniasis.
AB  - Sera from 61 Indian patients with visceral leishmaniasis caused by infection with
      Leishmania donovani were tested for the presence of T helper 1 (Th1) cell
      (interferon-gamma [IFN-gamma]) and Th2 cell-associated cytokines (interleukin-4
      [IL-4] and IL-10). The IFN-gamma activity was detected in 53%. IL-4 in 84%, and
      IL-10 in 56% of patient samples. Sera from 10 healthy Indian controls showed
      detectable IFN-gamma in 90%. IL-4 in 10%, and IL-10 in 20%; corresponding
      percentages for sera from eight healthy American controls were 100%, 12%, and 0%,
      respectively. Quantitative data for the 61 patients compared with the 10 Indian
      controls indicated comparable mean levels of IFN-gamma, but three- and 13-fold
      increases in IL-10 and IL-4, respectively. Undetectable IFN-gamma activity,
      observed in 47% of patients, was associated with the presence IL-4 alone or in
      combination with IL-10 but not with IL-10 alone. In patients who had failed prior
      therapy (n = 29) compared with previously untreated patients (n = 32). IFN-gamma
      levels were 67% lower and IL-4 levels were two-fold higher, IL-10 activity was
      comparable. These results using peripheral blood support the presence of a
      suppressive Th2 cell-associated immune response in symptomatic Indian kala-azar
      and point to a possible role for IL-4.

PMID- 9180603
TI  - Phase I trial of the SPf66 malaria vaccine in a malaria-experienced population in
      Southeast Asia.
AB  - In preparation for a recently reported, independent field trial of SPf66 malaria
      vaccine efficacy in Thailand, we first established the safety and immunogenicity
      of two clinical lots of U.S. manufactured lots of SPf66 in a series of
      overlapping Phase I studies. The vaccine was produced in approved laboratories
      using good manufacturing practices. Two clinical lots of alum-adsorbed SPf66 were
      evaluated in a combined, open-label, Phase I clinical trial involving 50 healthy,
      malaria-experienced Karen adults and children. Volunteers were grouped by age and
      immunized sequentially. Group 1 had 30 adults. Group 2 had 10 children 8-15 years
      of age, and Group 3 had 10 children 2-6 years of age. The SPf66 vaccine was well
      tolerated in this malaria-experienced population. The most common side effects
      were erythema, induration, warmth, and tenderness at the site of injection, which
      typically resolved within 24-48 hr. One adult volunteer developed an acute
      urticarial rash following the third dose. Among adults, and to a lesser extent
      older children females had more local reactions than their male counterparts.
      Seroconversion to SPf66 by enzyme-linked immunosorbent assay occurred in 76% of
      volunteers receiving two or three doses. This vaccine was safe and immunogenic in
      malaria-experienced Karen adults and children. This study establishes the
      comparability of U.S.-manufactured SPf66 with that of Colombian origin, and is
      important for interpreting the efficacy results of U.S.-manufactured SPf66 in the
      same study population.

PMID- 9180604
TI  - Volunteer studies investigating the safety and efficacy of live oral El Tor
      Vibrio cholerae O1 vaccine strain CVD 111.
AB  - A live oral cholera vaccine should ideally protect against both classical and El
      Tor biotypes of Vibrio cholerae O1. An El Tor biotype vaccine strain, therefore,
      would complement classical cholera vaccine strain CVD 103-HgR, a strain already
      in use in some countries. In this study, 25 healthy adult volunteers received a
      single dose of 10s colony-forming units of El Tor vaccine strain CVD 111, a
      derivative of El Tor Ogawa strain N16117 deleted in the virulence cassette. Three
      (12%) volunteers developed mild diarrhea (mean stool volume = 813 ml) but no
      systemic symptoms; 23 (92%) of the 25 volunteers developed serum vibriocidal
      antibodies (geometric mean titer = 1:2,291). Five weeks after vaccination, 18
      vaccines and eight uninimunized control volunteers underwent wild-type challenge
      with El Tor Ogawa strain 3008. Three (16.7%) of 18 vaccinees and seven (87.5%) of
      eight controls developed diarrhea (P = 0.001) (vaccine efficacy = 80.9%). Further
      studies are underway to determine a dosage of CVD 111 that will be more
      clinically acceptable but equally immunogenic and protective.

PMID- 9180605
TI  - Daily dynamics of Plasmodium falciparum subpopulations in asymptomatic children
      in a holoendemic area.
AB  - Plasmodium falciparum is the major cause of malaria morbidity and mortality in
      the world. Biologic and antigenic diversity is a characteristic of this parasite
      and infections can consist of several genetically diverse parasites. The daily
      dynamics of these parasite subpopulations were investigated in asymptomatic
      children in rural Tanzania. Fingerprick blood samples were collected on 14
      consecutive days from 20 children. Parasite densities were detected by light
      microscopy and genotyping of P. falciparum was done using a nested polymerase
      chain reaction (PCR) assay targeting polymorphic regions on the merozoite surface
      protein-1 (MSP-1), MSP-2, and glutamine-rich protein (GLURP) genes. In the eight
      children harboring P. falciparum throughout the study period, infections were
      found to be highly complex with daily changes in both parasite density and
      genotypic pattern. A nonrandom. 48-hr periodicity in these fluctuations suggests
      that P. falciparum infections consist of inherently synchronous subpopulations of
      parasites. These findings have important biologic and epidemiologic implications
      since one blood sample may only partly reflect the whole parasite population in
      an infected individual.

PMID- 9180606
TI  - Isolation and characterization of pirital virus, a newly discovered South
      American arenavirus.
AB  - Specific rodent species are principal hosts for each of the well-characterized
      members of the virus family Arenaviridae. Guanarito virus (Arenaviridae) is the
      etiologic agent of Venezuelan hemorrhagic fever. A previous study on the
      epidemiology of Venezuelan hemorrhagic fever revealed extensive arenavirus
      infection (presumed to be caused by Guanarito virus) in two rodent species.
      Sigmodon alstoni and Zygodontomys brevicauda, collected from the region of
      Venezuela in which the disease is endemic. In the present study, four arenavirus
      isolates recovered from the Municipality of Guanarito (two isolates each from S.
      alstoni and Z. brevicauda) were characterized to learn more about the natural
      rodent host relationships of Guanarito virus. Serologic tests and analyses of
      nucleocapsid protein gene sequence data indicated that the two isolates from Z.
      brevicauda are strains of Guanarito virus and that the two isolates from S.
      alstoni are representatives of a novel New World arenavirus (proposed name
      Pirital) that is antigenically and phylogenetically distinct from all known New
      World arenaviruses. The results of the present study provide further evidence
      that the cane mouse Z. brevicauda is a natural host of Guanarito virus and
      suggest that the cotton rat S. alstoni is the natural reservoir host of Pirital
      but not Guanarito virus.

PMID- 9180607
TI  - Experimental infection of nonhuman primates with sandfly fever virus.
AB  - Due to the lack of an animal model, previous studies of sandfly fever have relied
      upon human challenge trials. We examined the infectivity and potential
      pathogenicity of sandfly fever virus in cynomolgus monkeys (Macaca fascicularis).
      Three different preparations of sandfly fever virus. Sicilian strain, and a
      placebo were compared by different routes of administration. The most notable
      postchallenge clinical event was a decrease in lymphocytes in the intramuscularly
      challenged monkeys. Plaque-reduction neutralization responses peaked earlier in
      animals challenged intravenously as compared with those in animals challenged
      intramuscularly. There was no evidence for neurotropism or meningeal
      inflammation. Sandfly fever virus was infectious for cynomolgus monkeys, but
      produced no detectable clinical disease that might serve as a marker for animal
      modeling studies. On the other hand, the preclinical data provide supportive
      evidence for safe parenteral administration of a Sicilian strain of sandfly fever
      virus inoculum to humans as a challenge model for sandfly fever disease.

PMID- 9180608
TI  - Prevalence of human retroviral infection in Quillabamba and Cuzco, Peru: a new
      endemic area for human T cell lymphotropic virus type 1.
AB  - An epidemiologic study was conducted to determine the prevalence of retroviral
      infections among people of Qucchua origin in Cuzco and Quillabamba, Peru. The
      study volunteers included individuals at low and at high risk for retroviral
      infections. Each volunteer was interviewed to obtain clinical and epidemiologic
      data, and to identify risk behaviors for infection. The serum was tested for
      human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus
      types 1/2 (HTLV-1/2) by standard enzyme-linked immunosorbent and Western blot
      assays. Among a total of 370 volunteers enrolled in the study, 276 were women and
      94 were men whose ages ranged between 15 and 49 years. Infection with HTLV-1 was
      demonstrated in 5.1% (19 of 370), and one of these, a homosexual, was also
      positive for HIV-1; none had HTLV-2. Overall, the rate of HTLV-1 infection was
      5.3% (5 of 94) for males and 5% (14 of 276) for females. Among the low risk group
      of 211 healthy pregnant women, five (2.3%) were positive for HTLV-1. The rate of
      HTLV-1 infection in this group was significantly correlated with a history of
      dental surgery, as well as other surgical procedures, and a history of jaundice.
      Among the volunteers who practiced risk behavior(s) for retroviral infections,
      the positive rates for HTLV-1 were 13.7% (7 of 51) for female sex workers, 6.2%
      (3 of 48) for homosexuals and/or bisexuals, 8.5% (4 of 47) for patients with
      sexually transmitted diseases (STDs), and 0.0% (0 of 13) for promiscuous
      heterosexual males. In female sex workers. HTLV-1 infection was found to be
      significantly associated with age, a history of STDs or genital ulcers, sexual
      intercourse during menses, and vaginal douching (P < 0.05). A low prevalence of
      HIV-1 infection indicates that the virus has not yet spread significantly in
      these areas.

PMID- 9180609
TI  - Risk factors in dengue shock syndrome.
AB  - Despite a growing body of evidence predominantly, but not exclusively, from
      Thailand suggesting that the risk of developing dengue shock syndrome (DSS) is
      greatest following an anamnestic dengue infection, particularly if the most
      recent infection was with dengue 2 virus, there continues to be debate about the
      justification for these claims. This report describes a five-year, prospective
      study in two townships (suburbs) in Yangon (Rangoon) Myanmar (Burma) in which
      attempts were made to confirm the data from an earlier prospective study in
      Thailand and to address some of the criticism of earlier studies. This
      investigation found the incidence of anamnestic dengue infections in DSS patients
      to be significantly higher than in the community from which they were drawn and a
      significantly higher risk of developing DSS following an anamnestic infection
      (particularly with dengue 2 virus) than following a primary infection with any
      serotype.

PMID- 9180610
TI  - Chloroquine-resistant Plasmodium falciparum malaria: report of two locally
      acquired infections in Saudi Arabia.
AB  - We report here two cases of Saudi patients who acquired chloroquine-resistant
      Plasmodium falciparum locally, without any history of foreign travel, blood
      transfusion, or drug abuse. Both were satisfactorily treated, the first with
      quinine and a pyrimethamine-sulfadoxine combination, and the other with quinine
      and tetracycline. These two cases suggest either the possible establishment of
      chloroquine-resistant P. falciparum in Saudi Arabia, or the beginning of the
      spread of resistant strains from countries with established resistance to this
      country. Diligent notification of cases by attending physicians to the Ministry
      of Health will help to achieve effective control.

PMID- 9180611
TI  - Immunity to tetanus and diphtheria in rural Africa.
AB  - To assess the effect of the Expanded Program on Immunization (EPI) in rural
      Africa, blood samples were collected in two Kenyan sublocations. Serum antibodies
      against tetanus toxoid were measured in 155 individuals 1-70 years of age. Titers
      greater than the protective level of 0.01 IU/ml were found in 47% of the
      population. Protection was significantly higher in children born after the
      launching of the EPI (68%) and in women who had been at childbearing age since
      then (69%). Significantly lower protection was demonstrated in other age and sex
      groups. The level of protection in children was equal in the two populations,
      whereas protection in fertile women was significantly lower in the population
      living a long distance from a health center. Diphtheria anti-toxin was measured
      in the samples from one sublocation, and 70 of 84 individuals (83%) had antibody
      levels greater than the protective level. No age or sex difference could be
      found, and there was no correlation between response levels to diphtheria and
      tetanus. This implicates natural infections as an important source of diphtheria
      antibodies. Our findings demonstrate a need for better coverage of the adult
      population against tetanus. Furthermore, diphtheria transmission still appears to
      take place, underscoring the importance of diphtheria vaccination of travelers to
      rural Africa.

PMID- 9180612
TI  - The contribution of repellent soap to malaria control.
AB  - A study about the acceptability, protective efficacy, effectiveness, and cost of
      a repellent soap containing 20% diethyltoluamide and 0.5% permethrin was carried
      out on the Pacific coast of Ecuador and Peru, where malaria is endemic and the
      transmission is seasonal. The malaria vectors were Anopheles albimanus, An.
      punctimacula, and An. pseudopunctipennis in Ecuador and An. albimanus in Peru.
      Comparing the hourly mosquito bites on human subjects with and without the
      protection of the repellent soap, it showed that inactive, protected subjects
      were bitten 94.2% less than unprotected controls 2 hr after application of the
      soap. This protective efficacy was reduced to 81% after 6 hr. In persons
      physically active for 3 hr after application, the efficacy of the soap was 67% in
      the fourth hour after application and 52% in the sixth hour after application.
      Sweating decreased the protective efficacy of the soap even more. In a community
      based malaria control program, the soap was introduced by community health
      promoters. Acceptance was good when it was given free of charge but reduced
      dramatically when it was sold. People used the soap mainly because of the
      nuisance of mosquitoes. The application was generally done correctly. However, no
      significant impact on the incidence of malaria episodes could be shown when
      comparing intervention communities with control communities, either in Ecuador,
      where the proportion of Plasmodium falciparum cases was high, or in Peru, where
      P. vivax was the only species of Plasmodium seen. This can probably be explained
      by the limited use of soap and the shift of mosquito bites from users to nonusers
      of the repellent soap. The cost of a soap program would be $4.60 (USA) per person
      per year, which seems to be quite high in terms of cost of soap and its
      distribution related to people's low cash income. The implications of the
      introduction of repellent soap into a control program are discussed.

PMID- 9180613
TI  - A comparison of three methods for estimating the requirements for medical
      specialists: the case of otolaryngologists.
AB  - OBJECTIVE: To compare three methods of computing the national requirements for
      otolaryngologists in 1994 and 2010. DATA SOURCES: Three large HMOs, a Delphi
      panel, the Bureau of Health Professions (BHPr), and published sources. STUDY
      DESIGN: Three established methods of computing requirements for otolaryngologists
      were compared: managed care, demand-utilization, and adjusted needs assessment.
      Under the managed care model, a published method based on reviewing staffing
      patterns in HMOs was modified to estimate the number of otolaryngologists. We
      obtained from BHPr estimates of work force projections from their demand model.
      To estimate the adjusted needs model, we convened a Delphi panel of
      otolaryngologists using the methodology developed by the Graduate Medical
      Education National Advisory Committee (GMENAC). DATA COLLECTION/EXTRACTION
      METHODS: Not applicable. PRINCIPAL FINDINGS: Wide variation in the estimated
      number of otolaryngologists required occurred across the three methods. Within
      each model it was possible to alter the requirements for otolaryngologists
      significantly by changing one or more of the key assumptions. The managed care
      model has a potential to obtain the most reliable estimates because it reflects
      actual staffing patterns in institutions that are attempting to use physicians
      efficiently. CONCLUSIONS: Estimates of work force requirements can vary
      considerably if one or more assumptions are changed. In order for the managed
      care approach to be useful for actual decision making concerning the appropriate
      number of otolaryngologists required, additional research on the methodology used
      to extrapolate the results to the general population is necessary.

PMID- 9180614
TI  - Utilization of home care among people with HIV infection.
AB  - OBJECTIVE: To examine factors affecting the utilization of formal and informal
      home care services by people with HIV infection. DATA SOURCES AND STUDY SETTING:
      Study participants are adults with HIV infection receiving services at major
      providers of medical care in ten U.S. cities. Six interviews were conducted over
      an 18-month period (March 1991 to September 1992). DATA COLLECTION METHODS: Data
      on home care utilization, personal background characteristics, insurance status,
      and functional status are based on self-report. Disease stage is based on medical
      record data. STUDY DESIGN: This is an observational study using a panel survey
      design. Cross-tabular and longitudinal regression analyses (N = 1,727) were
      conducted to determine the effects of sociodemographic factors, functional
      status, disease stage, and insurance status on the receipt of home care from
      nurses, paraprofessionals, other professional providers, household residents,
      nonresident family and friends, and volunteers. PRINCIPAL FINDINGS: Over a 12
      month period, 16 percent of respondents received home nursing visits; 11 percent
      received paraprofessional care (e.g., nurse's aides, helpers); 4 percent received
      help from volunteers; 11 percent from non-resident family or friends, and 21
      percent from household members. Among the subgroup with AIDS (n = 837),
      corresponding percentages were 29, 20, 7, 17, and 29 percent for each provider
      type. In multivariate analyses, illness stage and functional status had strong
      effects on odds of utilization. Blacks and Hispanics were less likely than whites
      to have nursing care, but racial/ethnic group did not affect receipt of informal
      care. CONCLUSIONS: Home care utilization is concentrated among people with AIDS,
      compared to those at less advanced disease stages. In addition to functional
      limitations, fatigue is associated with the use of home care. Nursing and non
      nursing home care have somewhat different correlates. Medicaid may provide better
      coverage of personal care services than private insurance.

PMID- 9180615
TI  - The effect of chain membership on hospital costs.
AB  - OBJECTIVE: To compare the cost structures of hospitals in multihospital systems
      and independently owned hospitals. DATA SOURCES: The American Hospital
      Association's Annual Survey from 1990 for data on hospital costs and attributes.
      Area characteristics came from the Area Resource File, and the Medicare case-mix
      index came from the Health Care Financing Administration. Data on wages are from
      the Bureau of the Census' State and Metropolitan Area Data Book. The Guide to
      Hospital Performance from HCIA, Inc. provided data on quality of care. STUDY
      DESIGN: Separate cost functions were estimated for chain and independent
      hospitals. Hybrid translog cost functions included measures of outputs, input
      prices, and hospital and area characteristics. The estimation method accounted
      for the simultaneous determination of costs and chain membership, and for any
      nonrandom selection of hospitals into chains. Several economic cost measures were
      calculated to compare the cost structures of the two types of hospitals. DATA
      EXTRACTION METHODS: Data from all sources were merged at the hospital level to
      form the study sample. PRINCIPAL FINDINGS: Hospitals in multihospital systems
      were less costly than independently owned hospitals. Among independent hospitals,
      for-profits had the highest costs. There were no statistically significant
      differences in costs by ownership among chain members. Economies of scale were
      enjoyed in both types of hospitals only at high volumes of output, while
      economies of scope occurred at all volumes for chain hospitals, but only at low
      and medium volumes for independent hospitals. CONCLUSIONS: This study provides
      support for the idea that growth of the multihospital system sector can provide a
      market solution to the problem of constraining costs. It does not, however,
      support the property rights theory that proprietary hospitals are more efficient
      than nonprofit hospitals.

PMID- 9180616
TI  - Factors contributing to practice variation in post-stroke rehabilitation.
AB  - OBJECTIVE: To analyze geographic variability in the utilization and cost of post
      stroke medical care using multiple linear regression. DATA SOURCES/STUDY SETTING:
      A 20 percent random sample of Medicare beneficiaries with an admission to an
      acute care hospital for stroke during the first six months of 1991, supplemented
      by data from their Medicare claims and beneficiary records, the Medicare Cost
      Reports for hospitals and nursing homes, and the Area Resource File. STUDY
      DESIGN: Weighted least squares regression is used to analyze variations in post
      stroke practice patterns across 151 MSAs (Metropolitan Statistical Areas).
      Average post-stroke costs, utilization rates, and facility lengths of stay are
      regressed on patient and market characteristics. DATA COLLECTION/EXTRACTION
      METHODS: For a six-month post-stroke interval, beneficiary-level post-stroke
      costs and service utilization are averaged by MSA. Variables describing market
      conditions are then added to these MSA-level records. PRINCIPAL FINDINGS: Patient
      variables rarely explain more than a third of practice variation, and often they
      explain substantially less than that. Market variables (with some exception) tend
      to be relatively less important. Finally, one-half to two-thirds of the practice
      variation across MSAs is unexplained by the patient and market factors measured
      in our data. CONCLUSIONS: A substantial portion of inter-MSA variability in
      utilization and intensity of post-stroke rehabilitation services cannot be
      explained by differences in patient characteristics. Given the large practice
      differences observed across MSAs, it seems unlikely that unmeasured patient
      differences can account for much more of the practice differences.

PMID- 9180617
TI  - Complications, comorbidities, and mortality: improving classification and
      prediction.
AB  - OBJECTIVE: First, to compare the distribution of complications and comorbidities
      associated with 17 common surgical procedures. We then describe the effect of
      augmenting an ICD-9-CM version of the Charlson comorbidity index, given the
      possible confounding of comorbidities and complications, for three common
      inpatient surgical procedures: coronary artery bypass surgery, pacemaker surgery,
      and hip fracture repair. DATA SOURCES AND STUDY SETTING: Individuals having one
      of the above procedures between April 1, 1990 and March 31, 1994, identified from
      Manitoba Health hospital discharge data, and their extracted records. STUDY
      DESIGN: Design was cross-sectional and longitudinal using Manitoba data on
      hospital utilization and mortality. DATA COLLECTION/EXTRACTION: Manitoba hospital
      discharge abstracts permit identifying whether or not the diagnosis represents an
      in-hospital complication of care. Two data sets were created for each procedure,
      one including complication diagnoses and another with complications removed.
      PRINCIPAL FINDINGS: The degree to which complications contaminated estimation of
      comorbidity depended both on the procedures studied and on the covariates
      selected. The unique structure of the algorithm for the Charlson comorbidity
      index led to complication diagnoses having only a minor effect on the comorbidity
      score generated. Unless a data set affords the opportunity to remove complication
      diagnoses, the improvement in comorbidity detection afforded by augmenting the
      Charlson index, combined with the potential for overestimation of comorbidity,
      seem sufficiently modest to contraindicate such augmentation.

PMID- 9180619
TI  - British Cardiac Society Annual Conference. Manchester, 20-22 May 1997. Abstract.

PMID- 9180618
TI  - Normative models and healthcare planning: network-based simulations within a
      geographic information system environment.
AB  - OBJECTIVES: Network analysis to integrate patient, transportation and hospital
      characteristics for healthcare planning in order to assess the role of geographic
      information systems (GIS). A normative model of base-level responses of patient
      flows to hospitals, based on estimated travel times, was developed for this
      purpose. DATA SOURCES/STUDY SETTING: A GIS database developed to include patient
      discharge data, locations of hospitals, US TIGER/Line files of the transportation
      network, enhanced address-range data, and U.S. Census variables. The study area
      included a 16-county region centered on the city of Charlotte and Mecklenburg
      County, North Carolina, and contained 25 hospitals serving nearly 2 million
      people over a geographic area of nearly 9,000 square miles. STUDY DESIGN:
      Normative models as a tool for healthcare planning were derived through a spatial
      Network analysis and a distance optimization model that was implemented within a
      GIS. Scenarios were developed and tested that involved patient discharge data
      geocoded to the five-digit zip code, hospital locations geocoded to their
      individual addresses, and a transportation network of varying road types and
      corresponding estimated travel speeds to examine both patient discharge levels
      and a doubling of discharge levels associated with total discharges and DRG 391
      (Normal Newborns). The Network analysis used location/allocation modeling to
      optimize for travel time and integrated measures of supply, demand, and
      impedance. DATA COLLECTION/EXTRACTION METHODS: Patient discharge data from the
      North Carolina Medical Database Commission, address-ranges from the North
      Carolina Institute for Transportation Research and Education, and U.S. Census
      TIGER/Line files were entered-into the ARC/INFO GIS software system for analysis.
      A relational database structure was used to organize the information and to link
      spatial features to their attributes. PRINCIPAL FINDINGS: Advances in healthcare
      planning can be achieved by examining baseline responses of patient flows to
      distance optimization simulations and healthcare scenarios conducted within a
      spatial context that uses a normative model to integrate characteristics of
      population, patients, hospitals, and transportation networks. Model runs for the
      defined scenarios indicated that a doubling of the 1991 patient discharge levels
      resulted in an areal constriction of the service areas to those zip codes
      immediately adjacent to the hospitals, thereby leaving substantial areas
      unassigned to hospitals during the allocation process, but that doubling the
      demand for obstetrics care (DRG 391) resulted in little change in the pattern of
      accessibility to care as indicated by the size, orientation, and pattern of the
      service areas. CONCLUSIONS: The GIS-Network system supported "what if"
      simulations, portrayed service areas within a spatial context, integrated
      disparate data in the execution of the location/allocation model, and used
      estimated travel time along a transportation network instead of Euclidean
      distance for calculating accessibility. The results of the simulations suggest
      that the GIS-Network system is an effective approach for exploring a variety of
      healthcare scenarios where changes in the supply, demand, and impedance variables
      can be examined within a spatial context and where variations in system
      trajectories can be simulated and observed.

PMID- 9180620
TI  - Age-related changes in total arterial capacitance from birth to maturity in a
      normotensive population.
AB  - We evaluated the effect of body growth and aging on the ratio of
      echocardiographic (Teichholz) stroke volume to pulse pressure (SV/PP ratio) in
      373 normal-weight, normotensive children to adolescents (1 day to 17 years old;
      166 girls, 87 nonwhite) and 393 normal adults (17 to 85 years old; 164 women, 112
      nonwhite). Stroke volume increased with age in children (r = .64, P < .0001) and
      was stable in adults; pulse pressure decreased slightly with age in children (r =
      -.10, P = .06) and increased in adults (r = .29, P < .0001). As a consequence,
      SV/PP ratio increased with age in children (r = .51, P < .0001) and decreased in
      adults (r = -.18, P = .0004). To control for changes in body size that influence
      the size of the arterial tree, we used ANCOVA to adjust SV/PP for body size. Body
      size-adjusted SV/PP ratio was no longer related to age in children, whereas the
      negative relation with aging in adults remained statistically significant (r = 
      .19, P < .0002). Heart rate was negatively related to SV/PP ratio in both
      children and adolescents and adults, but this relation did not influence the
      relation with age. In multivariate analysis, high SV/PP ratio was predicted by
      greater height (P < .002) and weight (P < .04) and nonwhite race (P < .001) in
      children and adolescents and by younger age (P < .0001), greater weight (P <
      .0001), and low heart rate (P < .001) in adults. Sex did not enter the regression
      models. Thus, (1) SV/PP ratio is a measure of increasing capacity of the arterial
      tree during growth, whereas it depends on arterial compliance during adulthood
      through old age; (2) arterial compliance decreases progressively with aging; (3)
      the apparent difference between males and females might be due to their different
      body sizes.

PMID- 9180621
TI  - Prognostic significance of the white coat effect.
AB  - The difference between clinic and ambulatory blood pressure (BP) has been used to
      quantify the pressure reactivity to the doctor's visit (white coat effect). We
      investigated the prognostic significance of the clinic-ambulatory BP difference
      in the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale
      (PIUMA) study. A total of 1522 subjects contributed 6371 person-years of
      observation. All subjects had an initial off-therapy diagnostic workup including
      24-hour noninvasive ambulatory BP monitoring. The predicted values of ambulatory
      BP progressively diverged from the identity line (white coat effect of 0 mm Hg)
      with increasing clinic BP, but the predicted values of clinic BP tended toward
      the identity line with increasing ambulatory BP. Hence, the clinic-ambulatory BP
      difference showed a direct association with clinic BP and an inverse association
      with ambulatory BP. Consequently, a high clinic-ambulatory BP difference
      predicted both a high clinic and a low ambulatory BP, whereas a low clinic
      ambulatory BP difference predicted both a low clinic and a high ambulatory BP.
      The clinic-ambulatory BP difference showed also a direct association with age.
      During up to 9 years of follow-up (mean, 4.2 years), there were 157 major
      cardiovascular morbid events (125 nonfatal and 32 fatal). The rate of total
      cardiovascular morbid events did not differ (log-rank test) among the four
      quartiles of the distribution of the clinic-ambulatory BP difference (2.13, 2.92,
      2.10, and 2.83 events per 100 patient-years for systolic BP and 2.94, 2.14, 2.58,
      and 2.16 events per 100 patient-years for diastolic BP). Also, the rate of fatal
      cardiovascular events did not differ among the four quartiles of the distribution
      of the clinic-ambulatory BP difference. The clinic-ambulatory BP difference,
      taken as a measure of the white coat effect, does not predict cardiovascular
      morbidity and mortality in subjects with essential hypertension.

PMID- 9180622
TI  - Placebo-controlled biofeedback blood pressure effect in hypertensive humans.
AB  - The role of biofeedback in blood pressure control remains ill-defined because of
      nonspecific (placebo) effects, small study numbers, and the technical limitations
      of continuous pressure feedback. Clarification of its potential is awaited by
      those seeking a nonpharmacological approach to blood pressure control. This study
      examines the capability for systolic pressure lowering of 5 mm Hg or more using
      continuous pressure feedback in a statistical sample of untreated, well
      characterized, mildly hypertensive individuals. Subjects were randomized in a
      double-blind study to active or placebo biofeedback. Placebo consisted of a
      modified contingency approach, using a partial disguise based on a digital high
      pass filter with 15 elements. Blood pressure-lowering capability was assessed
      during two laboratory sessions. Continuous visual feedback resulted in 11 of 28
      subjects on active treatment and 12 of 28 on placebo treatment lowering their
      systolic pressure by 5 mm Hg or more (11 +/- 5.6 and 12 +/- 8.4 mm Hg,
      respectively; P = NS). Prestudy pressure was well-matched (153 +/- 9/97 +/- 4 and
      154 +/- 8/98 +/- 4 mm Hg, respectively). An initial small difference in diurnal
      profile did not change. These findings indicate that among mildly hypertensive
      individuals, almost half can lower systolic pressure at will for short periods.
      This capability is independent of the real or placebo nature of the feedback
      signal. We conclude that there is no specific short-term biofeedback pressure
      lowering capability in hypertensive individuals. Further exploration is needed to
      determine whether specific components of the placebo effect can be delineated,
      whether personality characteristics influence the response, and whether further
      biofeedback training can alter the outcome.

PMID- 9180623
TI  - Safety and feasibility of dobutamine-atropine stress testing in hypertensive
      patients.
AB  - Dobutamine stress testing is increasingly used for the diagnosis and functional
      evaluation of coronary artery disease. The aim of this study was to assess the
      hemodynamic profile, safety, and feasibility of dobutamine stress testing in
      hypertensive patients. Dobutamine (up to 40 micrograms/kg per minute)-atropine
      (up to 1 mg) stress echocardiography was performed for the detection of
      myocardial ischemia in 1164 patients with limited exercise capacity (age, 60 +/-
      12 years; 761 men); 446 patients were known to have hypertension. The test was
      considered feasible when 85% of the maximal heart rate and/or an ischemic end
      point (new or worsened wall motion abnormalities, ST segment depression, or
      angina) was achieved. No myocardial infarction or death occurred during the test.
      Dobutamine induced a significant increase of heart rate in patients with and
      without hypertension (59 +/- 25 and 63 +/- 23 beats per minute, respectively).
      Peak rate pressure product was similar in patients with and without hypertension
      (18,566 +/- 4584 and 18,230 +/- 4508). Hypotension (systolic pressure drop > 40
      mm Hg) during the test was more frequent in hypertensive patients (7% versus 4%
      in normotensive, P < .05). Independent predictors of hypotension were baseline
      systolic pressure greater than 140 mm Hg (odds ratio, 6.9; 95% confidence
      interval, 3.4 to 14), older age (odds ratio, 1.04; 95% confidence interval, 1.01
      to 1.07), and medication with calcium channel blockers (odds ratio, 1.8; 95%
      confidence interval, 1.1 to 3.5). The prevalence of ventricular tachycardia was
      similar (4.1%) in both groups. Episodes of 10 beats or more (0.06% of patients)
      were terminated promptly by intravenous metoprolol administration. Dobutamine
      stress testing was considered feasible in 91% of patients with and 92% of
      patients without hypertension. Dobutamine-atropine stress echocardiography is a
      safe and feasible method for the assessment of hypertensive patients referred for
      evaluation of myocardial ischemia. Despite the higher prevalence of dobutamine
      induced hypotension in these patients, the feasibility of the test is comparable
      to that in individuals without hypertension.

PMID- 9180624
TI  - Renin-angiotensin system components in the interstitial fluid of the isolated
      perfused rat heart. Local production of angiotensin I.
AB  - We used a modification of the isolated perfused rat heart, in which coronary
      effluent and interstitial transudate were separately collected, to investigate
      the uptake and clearance of exogenous renin, angiotensinogen, and angiotensin I
      (Ang I) as well as the cardiac production of Ang I. The levels of these compounds
      in interstitial transudate were considered to be representative of the levels in
      the cardiac interstitial fluid. During perfusion with renin or angiotensinogen,
      the steady-state levels (mean +/- SD) in interstitial transudate were 64 +/- 34%
      (P < .05 for difference from the arterial level, n = 8) and 108 +/- 42% (n = 6)
      of the arterial level, respectively; the levels in coronary effluent were not
      significantly different from those in interstitial transudate. Ang I was not
      detectable in interstitial transudate during perfusion with Tyrode's buffer or
      angiotensinogen. It was very low in interstitial transudate during perfusion with
      renin and rose to much higher levels during combined renin and angiotensinogen
      perfusion. The total production rate of Ang I present in interstitial fluid could
      be largely explained by the renin-angiotensinogen reaction in the fluid phase of
      the interstitial compartment. In contrast, the total production rate of Ang I
      present in coronary effluent and the net ejection rate of Ang I via coronary
      effluent were, respectively, 4.6 +/- 2.2 and 2.8 +/- 1.3 (P < .01 and P < .05 for
      difference from 1.0, n = 6) times higher than could be explained by Ang I
      formation in the fluid phase of the intravascular compartment. Ang I from the
      interstitial fluid contributed little to the Ang I in the intravascular fluid and
      vice versa. These data reveal two tissue sites of Ang I production, ie, the
      interstitial fluid and a site closer to the blood compartment, possibly vascular
      surface-bound renin. There was no evidence that the release of locally produced
      Ang I into coronary effluent and interstitial transudate occurred independently
      of blood-derived renin or angiotensinogen.

PMID- 9180625
TI  - Pressure natriuresis in salt-sensitive and salt-resistant Sabra rats.
AB  - Salt-resistant (SBN/y) and salt-sensitive (SBH/y) Sabra rats are a useful model
      of salt-sensitive hypertension with incompletely explored renal mechanisms. We
      investigated their pressure-natriuresis curves, with and without
      deoxycorticosterone acetate (DOCA)-salt treatment. To differentiate between
      extrinsic neural and hormonal mechanisms and intrinsic renal influences, we
      performed experiments with neural denervation, adrenalectomy, and infusions of
      vasopressin, norepinephrine, 17-hydroxycorticosterone, and aldosterone as well as
      without these maneuvers. In untreated SBN/y without controlled neural and
      circulating hormonal factors, urine flow and sodium excretion increased from 32
      to 95 microL/min per gram kidney weight (gkwt) and from 4 to 17 mumol/min per
      gkwt, respectively, as renal perfusion pressure was increased from 85 to 146 mm
      Hg. Renal blood flow and glomerular filtration rate were autoregulated and
      averaged 7.5 and 1.2 mL/min per gkwt. In untreated SBN/y with controlled neural
      and circulating factors, pressure-diuresis and -natriuresis curves were shifted
      toward the right, and renal blood flow and glomerular filtration rate ranged
      between 4.2 and 9.1 or 1 and 1.3 mL/min per gkwt as perfusion pressure was
      increased from 99 to 164 mm Hg. In both protocols, values in SBH/y did not
      differ. DOCA-salt increased blood pressure in SBH/y. In SBH/y without controlled
      neural and hormonal factors, pressure-diuresis and -natriuresis curves were
      shifted approximately 20 mm Hg toward the right. Fractional sodium and water
      excretion curves, renal blood flow, and glomerular filtration rate were shifted
      rightward in parallel. On the other hand, SBH/y with DOCA-salt and controlled
      neural and hormonal factors had lower sodium and water excretion rates only at
      the renal perfusion pressure of 150 mm Hg as well as decreased renal blood flow
      and glomerular filtration rate compared with DOCA-salt SBN/y. These data suggest
      that both extrinsic and intrinsic factors are responsible for reduced sodium and
      water excretory capacity in DOCA-salt SBH/y; however, the extrinsic factors may
      be more important.

PMID- 9180626
TI  - Effects of enalapril, losartan, and verapamil on blood pressure and glucose
      metabolism in the Cohen-Rosenthal diabetic hypertensive rat.
AB  - We undertook the present study to examine the effect of the angiotensin
      converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan,
      and calcium antagonist verapamil on systolic pressure and spontaneous blood
      glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain.
      Genetic hypertension and diabetes developed in this strain after crossbreeding of
      Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed
      their usual copper-poor sucrose diet, which is essential for the development of
      this model, and for 4 weeks received either enalapril, losartan, or verapamil.
      Systolic pressure was reduced significantly compared with controls in all treated
      groups. Chronic treatment with enalapril or verapamil, but not with losartan,
      succeeded in lowering spontaneous blood glucose, indicating improved diabetic
      control. Data suggest that angiotensin-converting enzyme inhibition by enalapril,
      but not angiotensin II antagonism by losartan, can improve glucose metabolism in
      addition to its hypotensive effect in a genetic diabetic hypertensive rat strain.
      This confirms that the drop in glucose with converting enzyme inhibition is
      highly dependent on bradykinin accumulation. Data further suggest that calcium
      channel blockade by verapamil can also improve glucose metabolism. The question
      remains whether the reduction in glucose by verapamil was a result of inhibition
      of glucogenesis.

PMID- 9180627
TI  - A 90-kD Na(+)-H+ exchanger kinase has increased activity in spontaneously
      hypertensive rat vascular smooth muscle cells.
AB  - Increased activity of the Na(+)-H+ exchanger (NHE-1 isoform) has been observed in
      cells and tissues from hypertensive humans and animals, including the
      spontaneously hypertensive rat (SHR). No mutation in NHE-1 DNA sequence or
      alteration in NHE-1 mRNA and protein expression has been demonstrated in
      hypertension, indicating that alterations in proteins that regulate NHE-1
      activity are responsible for increased activity. The recent finding that NHE-1
      phosphorylation in SHR vascular smooth muscle cells (VSMCs) was greater than in
      Wistar-Kyoto rat (WKY) VSMCs suggested that NHE-1 kinases may represent an
      abnormal regulatory pathway present in hypertension. To define NHE-1 kinases
      altered in the hypertensive phenotype. We measured NHE-1 kinase activity by an in
      gel-kinase assay using a recombinant glutathione S-transferase NHE-1 fusion
      protein as a substrate. At least 7 NHE-1 kinases (42 to 90 kD) were present in
      VSMCs. We studied a 90-kD kinase because it was the major NHE-1 kinase and
      exhibited differences between SHR and WKY. Comparison of 90-kD kinase activity
      revealed that SHR VSMCs had increased activity in growth-arrested cells and in
      cells stimulated by angiotensin II (100 nmol/L for 5 minutes). Activation of the
      90-kD kinase by angiotensin II was Ca2+ dependent, PKC independent, and partially
      dependent on the mitogen-activated protein kinase pathway. These findings
      indicate that increased activity of a 90-kD NHE-1 kinase is a characteristic of
      SHR VSMCs in culture and suggest that alterations in the 90-kD NHE-1 kinase
      and/or proteins that regulate its activity may be a pathogenic component in
      hypertension in the SHR.

PMID- 9180628
TI  - Lack of correlation between arterial and venous beta-adrenergic receptor
      sensitivity.
AB  - The regulation of vascular beta-adrenoceptor responses in humans has been studied
      in vivo in both arteries and veins. Because venous responses can be studied less
      invasively than arterial responses, they are an attractive substitute for the
      measurement of arterial responses, provided that venous responses are
      representative of responses in resistance arteries. However, although venous,
      particularly hand vein response, has been extensively studied, arterial and
      venous beta-adrenergic sensitivities, in the same individuals, have not been
      compared. Measures of venous and arterial beta-adrenergic sensitivities were
      compared in 10 healthy normotensive subjects. Forearm blood flow, after
      administration of increasing doses of isoproterenol into the brachial artery, was
      measured by strain-gauge plethysmography and was used for determination of
      arterial beta-adrenoceptor sensitivity, expressed as the IP500 (the dose of
      isoproterenol resulting in a fivefold [500%] increase in baseline forearm blood
      flow). Venous sensitivity to isoproterenol, expressed as the IP15 (the dose of
      isoproterenol resulting in 15% venodilation), was measured in a dorsal hand vein
      using the linear variable differential transformer. Administration of
      isoproterenol into the hand vein and brachial artery resulted in venodilation and
      increased forearm blood flow, respectively. However, there was no correlation
      between the measures of venous (log IP15) and arterial (log IP500) measures of
      vascular beta-adrenergic sensitivity (r = -.12, P = .74). We conclude that since
      arterial and venous sensitivities to isoproterenol in healthy white men did not
      correlate, venous and arterial beta-adrenergic responses are regulated
      differently and that studies examining vascular beta-adrenoceptor sensitivity
      would most appropriately be performed in a vessel representative of the vascular
      bed of interest.

PMID- 9180629
TI  - Effects of alcohol on sympathetic activity, hemodynamics, and chemoreflex
      sensitivity.
AB  - Alcohol intake has been shown to worsen obstructive sleep apnea and increase
      nocturnal hypoxemia. The mechanisms of this action are unclear. Animal studies
      suggest that a reduction in chemoreflex sensitivity may be implicated. Using a
      double-blind, randomized, vehicle-controlled design, we tested the hypothesis
      that oral alcohol intake depresses chemoreflex sensitivity in humans. We examined
      the effects of oral alcohol intake (1.0 g/kg body wt) on blood pressure, heart
      rate, heart rate variability, muscle sympathetic nerve activity, forearm vascular
      resistance, and minute ventilation in 16 normal male subjects. Peripheral and
      central chemoreflex sensitivity were measured in response to hypoxia (n = 10) and
      hypercapnia (n = 6), respectively. Plasma alcohol increased from 0 to 23.2 +/-
      1.5 mmol/L (107 +/- 7 mg/dL) at 60 minutes and 20.2 +/- 1 mmol/L (93 +/- 4 mg/dL)
      at 85 minutes after alcohol intake (P < .0001). Alcohol induced an increase in
      heart rate from 59 +/- 2 to 66 +/- 2 beats per minute (P < .01) and increased the
      ratio of low- to high-frequency variability of heart rate (P < .05). Although
      alcohol increased sympathetic nerve activity by up to 239 +/- 22% of baseline
      values (P < .01), forearm vascular resistance after alcohol was lower than that
      after vehicle (P < .05). Blood pressure did not increase compared with the
      vehicle session. Oxygen saturation during hypoxia after alcohol was 4 +/- 1%
      lower than it was during hypoxia after vehicle (P < .05) although arterial blood
      PO2 was unchanged. Alcohol did not affect the cardiovascular, sympathetic, or
      ventilatory responses to either hypoxia or hypercapnia. Acute increases in plasma
      alcohol increase heart rate and sympathetic nerve activity; blood pressure is not
      increased, probably because of vasodilator effects of alcohol. Alcohol does not
      alter chemoreflex responses to hypoxia or hypercapnia; thus, alterations in
      chemoreflex sensitivity are unlikely to explain the effects of alcohol on sleep
      apnea. Alcohol may reduce the affinity of hemoglobin for oxygen.

PMID- 9180630
TI  - Baroreflex control of heart rate and cardiac hypertrophy in angiotensin II
      induced hypertension in rabbits.
AB  - The cardiac hypertrophy observed in hypertension is thought to be responsible for
      the accompanying deficiency in the baroreflex control of heart rate. In this
      study, we assessed the baroreflex relationship between heart rate and arterial
      pressure on a group of seven rabbits during a normotensive period, during the
      early phase of angiotensin II (Ang II)-induced hypertension II week) (50 ng/kg
      per minute i.v. via osmotic minipumps), after 7 weeks of continuous hypertension,
      then 2 days after Ang II was stopped, and finally 7 days after Ang II. Left
      ventricles were weighed for measurement of left ventricular weight-body weight
      ratio. One week of intravenous Ang II infusion produced hypertension (mean
      arterial pressure from 80 +/- 2 up to 115 +/- 8 mm Hg), with significantly
      increased heart rate and hematocrit. The heart rate-arterial pressure baroreflex
      curve was shifted to the right, with a significant 45% reduction in the gain of
      the reflex (-6.4 +/- 1.5 to -3.5 +/- 0.2 beats per minute/mm Hg). After 7 weeks
      of Ang II, arterial pressure was still elevated (112 +/- 4 mm Hg) and the gain of
      the baroreflex curve still somewhat attenuated, although it was no longer
      markedly different from normotensive levels (gain, -5.09 +/- 0.95, 20% reduction
      from normotensive level). Two days after the Ang II infusion was stopped,
      arterial pressure had returned to normotensive levels, although hematocrit and
      heart rate remained elevated. At this time, the baroreflex curve was similar to
      prehypertensive control levels, with no further changes when measured again 7
      days after Ang II. Cardiac hypertrophy was present when measured at 7 days after
      angiotensin (left ventricular weight-body weight ratio: 1.78 +/- 0.05 versus 1.35
      +/- 0.04 g/kg, hypertensive versus normotensive, P < .05). Thus, although Ang II
      infusion produced an initial deficit in the baroreflex control of heart rate,
      this effect became less as the hypertension continued. Furthermore, although
      cardiac hypertrophy developed, its presence did not appear to be sufficient to
      produce a decrease in barosensitivity independent of raised arterial pressure.

PMID- 9180631
TI  - Sympathoexcitatory effect of hypothalamic/hypophysary inhibitory factor in rats.
AB  - We recorded changes in arterial blood pressure, heart rate, and renal sympathetic
      nerve activity in response to intracerebroventricular injection of bovine
      hypothalamic/hypophysary inhibitory factor and ouabain in conscious Wistar rats.
      Ouabain at 0.3 to 0.6 microgram caused dose-related increases in blood pressure,
      heart rate, and nerve activity (peak increases: 19 +/- 2 mm Hg, 42 +/- 4 beats
      per minute, and 48 +/- 4%, respectively; P < .05 versus basal). These responses
      were all blocked by central antibody Fab fragments, which bind ouabain and
      related steroids with high affinity. The inhibitory factor significantly
      increased blood pressure but decreased heart rate and nerve activity. Dose
      dependent increases in blood pressure as well as heart rate and nerve activity
      were observed when the inhibitory factor was injected after intravenous injection
      of the vasopressin antagonist D-(CH2)5Tyr-(Me)AVP. Central Fab fragments,
      however, did not affect these responses. Both ouabain and the inhibitory factor
      inhibited Na+,K+-ATPase activity in vitro. Fab fragments blocked this inhibition
      by ouabain but not by the inhibitory factor. These data indicate that the
      ouabainlike sympathoexcitatory effect of this factor is masked probably by a
      potent central effect on vasopressin release. In contrast to rat brain "ouabain,"
      this factor does not exhibit a high affinity for the Fab fragments, supporting
      the previous finding that this compound is structurally a nonouabain Na+,K+
      ATPase inhibitor.

PMID- 9180632
TI  - Shear stress augments expression of C-type natriuretic peptide and
      adrenomedullin.
AB  - Shear stress is known to dilate blood vessels and exert antiproliferative effects
      on vascular walls: these effects have been ascribed to shear stress-induced
      upregulation of endothelium-derived vasoactive substances, mainly nitric oxide
      and prostacyclin. We have demonstrated the significance of C-type natriuretic
      peptide (CNP) as a novel endothelium-derived relaxing peptide (EDRP) that shares
      a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that
      elevates intracellular cAMP as prostacyclin does. To elucidate the possible role
      of these EDRPs under shear stress, we examined the effect of physiological shear
      stress on CNP mRNA expression in endothelial cells derived from the human
      umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as
      well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated
      prominently in HUVECs under shear stress of 15 dyne/cm2 in a time-dependent
      manner (4 hours, sixfold increase compared with that in the static condition; 24
      hours, 30-fold increase). Similar results were obtained in BAECs (4 hours,
      twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold
      increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that
      was dependent on shear stress intensity was also observed (5 dyne/cm2, 2.5-fold
      increase of static; 15 dyne/cm2, 4.5-fold increase). Increased CNP secretion was
      also confirmed by the specific radioimmunoassay for CNP. Adrenomedullin mRNA
      expression in HUVECs increased under shear stress of 15 dyne/cm2 in a time
      dependent manner (4 hours, 1.2-fold increase of static: 24 hours, threefold
      increase) and shear stress intensity-dependent manner (15 dyne/cm2, threefold
      increase compared with that at 5 dyne/cm2). These results suggest that the
      coordinated augmentation of mRNA expression of these novel EDRPs may constitute
      shear stress-dependent vasodilator and antiproliferative effects.

PMID- 9180633
TI  - Adrenomedullary secretion of epinephrine is increased in mild essential
      hypertension.
AB  - To assess whether patients with mild essential hypertension have excessive
      activities of the sympathoneuronal and adrenomedullary systems, we examined total
      body and forearm spillovers and norepinephrine and epinephrine clearances in 47
      subjects with mild essential hypertension (25 men, 22 women, aged 38.1 +/- 6.7
      years) and 43 normotensive subjects (19 men, 24 women, aged 36.5 +/- 5.9 years).
      The isotope dilution method with infusions of tritiated norepinephrine and
      epinephrine was used at rest and during sympathetic stimulation by lower body
      negative pressure at -15 and -40 mm Hg. Hypertensive subjects had a higher
      arterial plasma epinephrine concentration (0.20 +/- 0.01 nmol.L-1: mean +/- SE)
      than normotensive subjects (0.15 +/- 0.01) (P < .01). The increased arterial
      plasma epinephrine levels appeared to be due to a higher total body epinephrine
      spillover rate in the hypertensive subjects (0.23 +/- 0.02 nmol.min-1.m-2) than
      the normotensive subjects (0.18 +/- 0.01) (P < .05) and not to a decreased plasma
      clearance of epinephrine. The arterial plasma norepinephrine level, total body
      and forearm norepinephrine spillover rates, and plasma norepinephrine clearance
      were not altered in the hypertensive subjects. The responses of the catecholamine
      kinetic variables to lower body negative pressure were not consistently different
      between normotensive and hypertensive individuals. These data indicate that
      individuals with mild essential hypertension (1) have elevated arterial plasma
      epinephrine concentrations that are due to an increased total body epinephrine
      spillover rate, indicating an increased adrenomedullary secretion of epinephrine;
      (2) have no increased generalized sympathoneuronal activity and no increased
      forearm norepinephrine spillover; and (3) have similar responses of both the
      sympathoneuronal and adrenomedullary systems to sympathetic stimulation by lower
      body negative pressure.

PMID- 9180634
TI  - Adrenomedullin is a potent inhibitor of angiotensin II-induced migration of human
      coronary artery smooth muscle cells.
AB  - The migration of coronary artery medial smooth muscle cells (SMCs) into the
      intima is proposed to be an important process of intimal thickening in coronary
      atherosclerotic lesions. In the current study, we examined the possible
      interaction of adrenomedullin, a novel vasorelaxant peptide, and angiotensin II
      (Ang II) on human coronary artery SMC migration using Boyden's chamber method.
      Ang II stimulated SMC migration in a concentration-dependent manner between 10(6)
      and 10(8) mol/L. This stimulation was clearly blocked by the Ang II type 1
      receptor antagonist losartan but not by the type 2 receptor antagonist PD 123319.
      The migration stimulatory effect of Ang II was chemotactic in nature for cultured
      human coronary artery SMCs but was not chemokinetic. Human adrenomedullin clearly
      inhibited Ang II-induced migration in a concentration-dependent manner. Human
      adrenomedullin stimulated cAMP formation in these cells. Inhibition by
      adrenomedullin of Ang II-induced SMC migration was paralleled by an increase in
      the cellular level of cAMP. 8-Bromo-cAMP, a cAMP analogue, and forskolin, an
      activator of adenylate cyclase, inhibited the Ang II-induced SMC migration. These
      results suggest that Ang II stimulates SMC migration via type 1 receptors in
      human coronary artery and adrenomedullin inhibits Ang II-induced migration at
      least partly through a cAMP-dependent mechanism. Taken together with the finding
      that adrenomedullin is synthesized in and secreted from vascular endothelial
      cells, this peptide may play a role as a local antimigration factor in certain
      pathological conditions.

PMID- 9180635
TI  - Cyclosporine impairs the ability of human platelets to mediate vasodilation.
AB  - Cyclosporine causes various platelet abnormalities. Whether it affects the
      ability of platelets to mediate vasodilation is unknown. Platelets were isolated
      from healthy volunteers and 13 heart transplant patients on cyclosporine. When
      perfused through preconstricted normal rabbit carotid arteries, activated
      platelets from transplant patients failed to cause vasorelaxation, whereas normal
      platelets produced significant vasodilation (-4.0 +/- 1.9% versus 30 +/- 3% [P <
      .0001] change in vessel diameter, respectively). When normal platelets were
      exposed to cyclosporine in vitro, they lost their ability to cause vasodilation
      in a dose- and time-dependent fashion. However, when activated and perfused
      through quiescent, N omega-nitro-L-arginine-pretreated arteries, platelets from
      transplant patients and normal platelets caused similar degrees of
      vasoconstriction. The amount of adenosine triphosphate in the supernatant from
      activated cyclosporine-exposed and control platelets was similar (1.7 +/- 0.4
      versus 1.5 +/- 0.3 mumol/L [P = NS], respectively). However, concomitant
      perfusion of activated platelets from transplant patients impaired acetylcholine
      mediated, endothelium-dependent vasodilation but perfusion of normal platelets
      did not. Although cyclosporine-exposed platelets showed an impaired ability to
      produce vasorelaxation, supernatant from the same platelets caused near normal
      vasodilation. Human platelets exposed to cyclosporine have an impaired ability to
      mediated vasodilation. This is not due to increased platelet-mediated
      vasoconstriction or a decrease in the release of platelet-derived nucleotides but
      rather to a short-acting compound released by cyclosporine-exposed platelets that
      interferes with endothelium-dependent vasodilation.

PMID- 9180636
TI  - Alterations in calcium stores in aortic myocytes from spontaneously hypertensive
      rats.
AB  - The aim of the present work was to further characterize intracellular calcium
      stores released by angiotensin II (Ang II) in spontaneously hypertensive rat
      (SHR) and Wistar-Kyoto rat (WKY) vascular smooth muscle cells (VSMCs) and to
      study their alterations associated with proliferation. Intracellular Ca2+
      concentration was monitored by image analysis in aortic myocytes loaded with fura
      2. In the presence of extracellular Ca2+, sensitivity to Ang II in proliferating
      VSMCs was not different in the two strains, but it increased 10-fold in confluent
      VSMCs from SHR-compared with those from WKY. In Ca(2)+-free medium, Ca2+ release
      induced by thapsigargin (10 mumol/L) was significantly greater (about twofold) in
      SHR than WKY, in both proliferating and confluent cultures, with responses during
      proliferation being 0.7-fold smaller. Responses to Ang II were abolished after
      exposure of the cells to thapsigargin. In proliferating cultures, ryanodine (10
      mumol/L) did not modify the rises in intracellular Ca2+ concentration induced by
      Ang II in VSMCs from both strains. Conversely, in confluent cultures, ryanodine
      reduced Ang II (100 nmol/L)-induced Ca2+ release to the same level as in
      proliferating cultures, and it suppressed the difference between SHR and WKY.
      These results show that the ryanodine-sensitive Ca2+ release induced by Ang II is
      enhanced in VSMCs from SHR at confluence and is impaired during proliferation.
      Thus, they suggest that differences in Ca2+(-)induced Ca2+ release from the
      sarcoplasmic reticulum may participate in increased responsiveness of VSMCs to
      Ang II in SHR and in phenotypic modulation of vascular myocytes during
      proliferation.

PMID- 9180637
TI  - Effects of age on Ca2+ currents in small mesenteric artery myocytes from Wistar
      Kyoto and spontaneously hypertensive rats.
AB  - The purpose of this study was to test the hypothesis that differences in voltage
      gated Ca2+ channels increase with age during the development of sustained
      hypertension in the spontaneously hypertensive rat (SHR). Using patch-clamp
      methods, we measured whole-cell Ca2+ currents in freshly isolated myocytes from
      small mesenteric arteries of juvenile (5 to 7 weeks), young (10 to 12 weeks), and
      mature (19 to 23 weeks) Wistar-Kyoto rats (WKY) and SHR. Indirect tail artery
      systolic pressure increased progressively with age in SHR (from 125 +/- 5 to 159
      +/- 5 to 192 +/- 5 mm Hg) but only in the younger WKY (from 107 +/- 6 to 130 +/-
      4 to 136 +/- 4 mm Hg). Peak Ca2+ current density (current per cell capacitance)
      was larger in SHR than WKY myocytes at all ages (at 6 weeks, 3.5 +/- 0.4 versus
      2.3 +/- 0.2 pA/pF; at 12 weeks, 3.8 +/- 0.2 versus 3.1 +/- 0.2; at 20 weeks. 4.9
      +/- 0.4 versus 3.3 +/- 0.4). Cell capacitance (surface area) was significantly
      smaller in 12-week-old SHR than WKY (25.2 +/- 1.1 versus 31.8 +/- 1.6 pF), but no
      differences were found in the 6- or 20-week-old groups. There were significant
      differences in Ca2+ current with strain, age, and voltage but no significant age
      strain interactions. The ratio of peak Ca2+ current for SHR to that of WKY
      declined linearly with voltage at all ages suggesting differences in the voltage
      dependence of Ca2+ current activation. The voltage dependence of Ca2+ current was
      shifted to the left in SHR compared with WKY at all ages. Activation curves were
      shifted significantly in the negative-voltage direction only in 20-week-old SHR
      myocytes. We have found differences with age in Ca2+ current density and its
      voltage dependence in SHR compared with WKY during the phase of development in
      which blood pressure becomes established in the SHR. The net effect of these
      differences predicts a larger Ca2+ current in SHR at voltages in the
      physiological range of membrane potential.

PMID- 9180638
TI  - Hypothalamic hypophyseal inhibitory factor (HHIF) increases intrasynaptosomal
      free calcium concentration.
AB  - We have isolated from bovine hypothalamic and pituitary tissues a sodium pump
      inhibitor that is structurally different from ouabain. By mass spectrometric
      analysis, this purified factor revealed a single unique molecular ion with an
      accurate mass of 412.277 and a mass spectra different from that of ouabain. It
      has been previously shown that this factor inhibits the Ca2+, Mg(2+)-ATPase of
      the plasma membrane of synaptosomes. Because Ca2+ plays a major role in cellular
      excitability, we carried out a systematic study of the effects of this inhibitor
      on the Ca2+ transport processes across the plasma membrane of synaptosomes: We
      measured ATP-dependent calcium uptake, Na(+)-Ca2+ exchange, and passive
      permeability using 45Ca2+ and Millipore filtration, chlortetracycline
      fluorescence, and light-scattering, respectively. This factor inhibits the Na+,
      K(+)-ATPase activity of the synaptosomal plasma membrane vesicles in the same
      range of concentrations that produced an increase of intrasynaptosomal free
      calcium, with nearly the same K0.5 value. In addition, in this concentration
      range, this factor stimulated 10- to 11-fold the passive flux of Ca2+ and 2.5- to
      3-fold the Ca2+ influx via the Na(+)-Ca2+ exchange in these membranes with
      respect to control values. Measurements of fluorescence anisotropy showed that in
      this concentration range, the inhibitor did not significantly change the order
      parameter (fluidity) of these membranes. These results suggest that besides its
      known inhibition of the sodium pump, this factor could play a role in the control
      of Ca2+ homeostasis by direct modulation of transport systems implicated in the
      control of intracellular calcium.

PMID- 9180639
TI  - Possible participation of nitric oxide in the increase of norepinephrine release
      caused by angiotensin peptides in rat atria.
AB  - In rat atria isolated with their cardioaccelerans nerves and labeled with
      [3H]norepinephrine, exposure to 1 x 10(-7) mol/L angiotensin II (Ang II) and 1 x
      10(-7) mol/L Ang-(1-7) increased the release of radioactivity elicited by nerve
      stimulation (0.5-millisecond-long square-wave pulses at 2 Hz during 2 minutes) by
      90% and 60%, respectively. The facilitatory effect on noradrenergic
      neurotransmission caused by both peptides was stereospecifically prevented by N
      omega-nitro-L-arginine methyl ester (1 x 10(-4) mol/L), an inhibitor of nitric
      oxide synthase that catalyzes the conversion of L-arginine to nitric oxide, as
      well as by 1 x 10(-5) mol/L methylene blue, a substance that inhibits the
      guanylate cyclase considered as the final target of nitric oxide action. On the
      other hand, the precursor of nitric oxide synthesis. L-arginine (1 x 10(-3)
      mol/L), reversed the prevention produced by N omega-nitro-L-arginine methyl ester
      on the increased release of norepinephrine caused by Ang II and Ang-(1-7). The
      present results suggest that nitric oxide could be involved in the
      neuromodulatory function elicited by both Ang II and Ang-(1-7) in rat atria. The
      physiological role of this observation is still under study.

PMID- 9180640
TI  - Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive
      rats.
AB  - We hypothesized that in female spontaneously hypertensive rats (SHR), estrogen
      moderates the dysfunction of arterioles by preserving nitric oxide synthesis. To
      this end, we conducted experiments on isolated gracilis muscle arterioles
      (approximately 55 microns in diameter) of 12-week-old (SHR divided into four
      groups: females (fSHR), ovariectomized females (fSHR-OV), ovariectomized females
      with estrogen replacement (fSHR-OV+ES, 50 micrograms/kg SC 17 beta-estradiol
      benzoate every 48 hours), and males (mSHR). Arteriolar diameter in the presence
      of perfusion pressures of 60, 80, 100, and 120 mm Hg were obtained, and diameter
      changes were measured (at 80 mm Hg) in response to various concentrations of
      substance P (10(-9) to 5 x 10(-8) mol/L), sodium nitroprusside (10(-8) to 10(-6)
      mol/L), and A23187 (5 x 10(-8) to 10(-6) mol/L). The pressure-induced diameter of
      mSHR and fSHR-OV arterioles was significantly less (by approximately 10%) than
      that of fSHR and fSHR-OV+ES arterioles. N omega-nitro-L-arginine (10(-4) mol/L),
      a nitric oxide synthase inhibitor, elicited a significant decrease in basal
      arteriolar diameter of fSHR (by approximately 19%) and fSHR-OV+ES (by
      approximately 17%), thereby eliminating the differences in tone among the various
      groups. Dilations of fSHR and fSHR-OV+ES arterioles to substance P were
      significantly greater (by 140% at a concentration of 5 x 10(-8) mol/L) than those
      of mSHR and fSHR-OV arterioles, whereas dilations to sodium nitroprusside were
      not different among the groups. A23187 (a nitric oxide releaser) elicited
      dilations in arterioles of fSHR (5.9 +/- 1.5%, 13.0 +/- 1.8%, and 19.2 +/- 2.1%)
      and fSHR-OV+ES (4.3 +/- 1.0%, 10.3 +/- 2.4%, and 15.0 +/- 4.0%) but constrictions
      in those of mSHR (-7.5 +/- 1.6%, -25.3 +/- 39%, and -36.9 +/- 4.1%) and fSHR-OV (
      2.6 +/- 1.7%, 7.4 +/- 3.3%, and -11.5 +/- 6.1%). We conclude that estrogen in
      fSHR is responsible for the preservation of nitric oxide synthesis in skeletal
      muscle arterioles, resulting in a greater modulation of pressure-induced myogenic
      tone than in mSHR and maintenance of nitric oxide-mediated dilations.

PMID- 9180641
TI  - Estrogen effects on nitric oxide release.

PMID- 9180642
TI  - Prognostic value of clinical variables in ovarian cancer.
AB  - OBJECTIVE: To test the hypothesis that clinical variables, including the
      patient's symptoms, symptom severity, and co-morbidity, affect the survival rate
      in patients with ovarian cancer. METHODS: We reviewed the records of 137 cases of
      ovarian cancer diagnosed and treated between January 1987 and June 1992, and
      extracted data regarding patients' demographic characteristics, symptoms, medical
      co-morbidity, stage of disease, tumor histology and grade, treatment, and
      clinical course. RESULTS: Once cases of borderline tumors were excluded, the
      overall 3-year and 4-year mortality rate were 38% and 49%, respectively. There
      was an decrease in 4-year survival with more advanced symptom type ranging from
      85% in asymptomatic women to 38% in women with complex symptoms (log rank, p =
      0.005). Medical co-morbidity was not found to affect survival in the cohort
      studied. We performed multivariable analysis using a Cox proportional hazards
      model and confirmed that the symptom stage was highly prognostic even after
      controlling for FIGO stage, age and co-morbidity (p = 0.004). CONCLUSION: We
      found that clinical variables such as patient's symptoms, were associated with
      prognosis. Symptom classification is a necessary and important component in a
      system of prognostic stratification for ovarian cancer.

PMID- 9180643
TI  - Estimating population-based incidence and prevalence of major coronary events.
AB  - Population-based data on major coronary events (MCE) are generally lacking for
      large areas, such as at the nationwide level. While mortality data are currently
      and exhaustively collected in all developed countries and in most developing
      countries, incidence and prevalence are often available only for certain
      subgroups of the population under study. We propose a mathematical method to
      estimate incidence and prevalence using morality and survival data as input, and
      to forecast MCE occurrence using an age, period, and cohort approach. An
      application of the method is given to reconstruct incidence and prevalence of MCE
      in Italy from 1970 to 1990 and to project trends up to the year 2000. MCE
      incidence has been decreasing since 1974, four years before the observed
      mortality decline. Conversely, prevalence continues to increase up to the middle
      of the 1980, and declines thereafter.

PMID- 9180644
TI  - Self-rated health status as a health measure: the predictive value of self
      reported health status on the use of physician services and on mortality in the
      working-age population.
AB  - The validity of various self-reported health assessments in predicting physician
      contracts and all-cause mortality was investigated in a prospective study in
      Finland. The follow-up periods were one year for the use of physician services
      and ten years ten months for the mortality. The study cohort comprised 1340 men
      and 1500 women, 35-63 years of age at the beginning of the study. The initial
      health assessments were derived from postal questionnaires in 1980 (response rate
      77.5%). The survey was repeated one year later to verify the stability of the
      respondents' perceived health status. The data on the physician contacts and
      mortality were registered independently. The stability of perceived health status
      was relatively good and the perceived health was inversely associated with the
      number of physician contacts per year. A consistent inverse association,
      standardized by age, sex and social status, was observed between perceived health
      status and perceived physical fitness and mortality, while the predictive value
      of self-reported chronic diseases was low. The results suggest that the
      subjective health assessments are valid health status indicator in middle-aged
      populations, and they can be used in cohort studies and population health
      monitoring.

PMID- 9180645
TI  - Assessing the responsiveness of a functional status measure: the Sickness Impact
      Profile versus the SIP68.
AB  - In this study, the Sickness Impact Profile (SIP) and the SIP68 are studied for
      their ability to detect changes in health-related behavioral status.
      Methodological approaches toward responsiveness are invented and discussed. Next,
      literature findings on the responsiveness of the SIP are presented and judged for
      their validity. The SIP appeared to be able to demonstrate changes in the
      expected direction and in accordance with changes detected by other instruments.
      Using data from seven different longitudinal projects in populations with
      different diagnoses, the responsiveness of both the SIP136 and the SIP68 are
      subsequently studied and compared. In all populations, changes in functional
      status were indicated by both instruments. In terms of effect sizes, the SIP136
      and the SIP68 do not differ significantly in their responsiveness. Moreover,
      changes detected by both SIPs appear to be valid representations of changes in
      health-related functional status.

PMID- 9180646
TI  - Validity of the Physical Activity Scale for the Elderly (PASE): according to
      energy expenditure assessed by the doubly labeled water method.
AB  - The study investigates the validity of the Physical Activity Scale for the
      Elderly (PASE) in 21 Dutch elderly men and women. The PASE is an easily scored,
      brief questionnaire for elderly, suitable for large epidemiologic studies. The
      PASE score was compared with physical activity measured with the doubly labeled
      water method. The correlation coefficient of the PASE score with the residuals
      from the regression analysis using total energy expenditure as dependent and
      resting metabolic rate as independent variate was 0.58 (95% CI = 0.50-0.81).
      Women had greater engagement in extremely high scoring activities as housework
      and taking care of others, resulting in higher PASE scores than men (97.9 and
      71.9). The higher scores in women were not linked to higher activity levels,
      which suggests that the mentioned activities may be overvalued. Sex specific
      correlation coefficients were 0.79 (CI = 0.32-0.95) and 0.68 (CI = 0.15-0.90) for
      men and women, respectively. In conclusion, the PASE proved to be a reasonable
      valid method to classify healthy elderly men and women into categories of
      physical activity. Some possible refinements were suggested, which may improve
      the accuracy of the PASE questionnaire.

PMID- 9180647
TI  - Assessing individual risk for breast cancer: risky business.
AB  - There is increasing demand for prediction of individual women's risk for breast
      cancer from women, clinicians, researchers, and health planners. Risk assessment
      for breast cancer is the process of identifying characteristics of an individual
      woman that are relevant to her risk, and combining those characteristics into a
      quantitative or qualitative risk profile. This article reviews and compares
      available methods of predicting risk, discusses benefits and drawbacks to the
      methods, and compares risk estimates for several hypothetical subjects using the
      different methods. Current and future uses for risk assessment are described.
      Risk assessment, while a promising tool for research now, and for clinical areas
      in the future, is still too imprecise for accurate prediction of breast cancer
      occurrence in individuals.

PMID- 9180648
TI  - Comparison of a generic to disease-targeted health-related quality-of-life
      measures for multiple sclerosis.
AB  - Evaluation of the relative contributions of generic and disease-targeted measures
      to assessing health-related quality of life (HRQOL) for chronic conditions is
      needed to help in selection of appropriate measures. We administered a generic
      HRQOL measure (the Short Form-36 [SF-36]), three disease-targeted supplemental
      scales to the SF-36, and two disease-targeted HRQOL instruments to 171 adults
      with multiple sclerosis. Most scales yielded adequate variability, internal
      consistency reliability, and test-retest reliability. The relationship between
      each measure and four primary "criterion" variables were assessed: overall
      symptom severity in the prior year; ambulation status; days unable to work or
      attend school in the prior month: and a rating of overall quality of life.
      Results indicate that the disease-targeted scales provided unique information not
      captured by the generic measure. We conclude that if a generic measure of HRQOL
      is desirable for a given study of multiple sclerosis, additional information will
      be gained by supplementing that measure with selected scales.

PMID- 9180649
TI  - Prediction of young adult blood pressure from childhood blood pressure, height,
      and weight.
AB  - To assess the ability of childhood blood pressure, height, and weight to predict
      young adult blood pressure, the authors examined data obtained over multiple
      visits for four years on 339 children aged 8-18 years in East Boston,
      Massachusetts. These subjects were again seen 8-12 years later when they were
      aged 20-26 years. Multivariate regression models were used to predict true blood
      pressure in young adulthood from observed childhood measurements closest to age
      10 (n = 219), adjusting for within-person variability. Without adjusting for
      childhood blood pressure, childhood height, weight and body mass index were at
      least marginally associated with young adult systolic blood pressure in boys and
      girls, with similar coefficients for each gender. The strongest predictor was
      weight (beta = 0.6 mmHg/10 lbs for girls, and beta = 0.7 mmHg/10 lbs for boys),
      and height was no longer predictive with weight in the model. With childhood
      blood pressure included, neither childhood height nor weight were predictors of
      future systolic blood pressure. However, change in height and weight were
      predictors of future systolic blood pressure. Weight change was a stronger
      predictor in girls than boys with beta = 0.9 mmHg/10 lbs. For diastolic blood
      pressure, height and weight had limited predictive ability in these data. These
      models, which allow for both between- and within-person variability in young
      adulthood, may be used to estimate the predictive value for future high blood
      pressure of a child's current blood pressure, height and weight, as well as
      future change in height and weight. These data suggest that the effects of
      childhood height and weight on future blood pressure may be negligible given
      childhood blood pressure, but that later height and weight remain predictive.

PMID- 9180650
TI  - Use of goal attainment scaling in measuring clinically important change in
      cognitive rehabilitation patients.
AB  - Measuring the effectiveness of cognitive rehabilitation programs poses both
      conceptual and practical challenges. We compared several standardized outcome
      measures with goal attainment scaling (GAS) to assess their sensitivity to
      changes in health status in patients undergoing cognitive rehabilitation. GAS is
      a measurement approach that accommodates multiple individual patient goals, and
      has a scoring system which allows for comparisons between patients. Forty-four
      patients were evaluated. GAS yielded a mean 4.4 goals per patient. The mean gain
      in the GAS score was compared with the change in the Rappaport Disability Rating
      Scale, the Kohlman Evaluation of Daily Living Skills, the Milwaukee Evaluation of
      Daily Living, the Klein-Bell elimination scale and mobility scale, the
      Instrumental Activities of Daily Living Scale, and the Spitzer Quality of Life
      Index. Using a relative efficiency statistic, GAS proved more responsive than any
      other measure. The effect size statistic also demonstrated greater responsiveness
      to change with GAS compared with standard measures. GAS shows promise as a
      responsive measure in cognitive rehabilitation. This study replicates a similar
      study of GAS in frail elderly patients, suggesting that individualized measures
      may have broad merit in evaluating rehabilitation programs.

PMID- 9180651
TI  - Incidence rates of falls among Japanese men and women living in Hawaii.
AB  - Japanese people in both Japan and in Hawaii have a lower incidence of hip
      fractures than white people in Hawaii or on the mainland of the United States.
      Hip fractures usually occur after a fall, and differing incidence rates of falls
      might contribute to the observed differences in hip fracture rates. To
      investigate this possibility we undertook a prospective study of falls among
      elderly Japanese men and women living in Hawaii using intensive surveillance
      methods similar to those used in studies of predominantly white populations. For
      our Japanese participants, the incidence rates of total falls were 139 per 1000
      person years for men and 276 per 1000 person years for women. Age adjusted rate
      ratios of falls for predominantly white populations compared with our Japanese
      participants ranged from 1.8 to 2.3 for women and from 2.6 to 4.7 for men. The
      risk of injuries when they did fall, however, was not lower for our Japanese
      participants than reported for white participants. For our Japanese population,
      past falls, female gender, and daytime hours were associated with an increased
      incidence of falls.

PMID- 9180652
TI  - Disability and handicap 5 years after a head injury: a population-based study.
AB  - A population-based cohort of 407 head trauma patients has been studied since 1986
      to estimate the prevalence of long-term disabilities and handicaps by means of a
      structured questionnaire. Five years later, 6-1 patients were deceased and 36
      were lost to follow-up. Prevalence of subjective and behavioral complaints was
      high whatever the initial head trauma severity. Lethality in severe head injuries
      was 56%, and half of the survivors remained disabled. In minor and moderate head
      injured patients, most disabilities were related to extracranial injuries. Taking
      all disabilities into consideration, each year 24 per 100,000 patients of such a
      population are likely to suffer from at least one long-lasting disability,
      including 10 per 100,000 whose disabilities are due to extracranial injuries.
      Head injuries induce long-lasting handicap in 9 per 100,000 habitants which is
      severe in 2 per 100,000. These figures point to the need of reinforcing
      preventive actions and long-term care of these patients.

PMID- 9180653
TI  - Sex and ethnic differences in use of myocardial revascularization procedures in
      Mexican Americans and non-Hispanic whites: the Corpus Christi Heart Project.
AB  - Age-adjusted rates of percutaneous transluminal coronary angioplasty (PTCA) and
      aortocoronary bypass surgery (ACBS) were determined for Mexican American (MA) and
      non-Hispanic white (NHW) patients hospitalized for coronary heart disease.
      Hypotheses of equal receipt of procedures between gender and ethnic groups were
      tested. Following myocardial infarction (MI), women were less likely than men to
      receive either procedure (22 versus 32%, p < 0.01), and MA were less likely than
      NHW to receive PTCA (13 versus 23%, p < 0.01) but not ACBS. After adjustment for
      extent of disease and other potential confounders, ethnic groups differed
      marginally in receipt of PTCA but not ACBS, while gender differences were not
      significant. Although women received revascularization procedures less frequently
      than men, this difference did not persist after controlling for extent of
      coronary artery disease by angiography: therefore, these observed differences in
      delivery of health care services may be appropriate. Mexican Americans received
      PTCA, but not ACBS, less frequently than NHW. This selective ethnic difference in
      receipt of PTCA does not appear to be associated with the extent of disease or
      other medical characteristics, and may represent inappropriate bias in delivery
      of health care services.

PMID- 9180654
TI  - Hormone replacement therapy and major risk factors for reproductive cancers,
      osteoporosis, and cardiovascular diseases: evidence of confounding by exposure
      characteristics.
AB  - Observational studies have yielded reports on long-term effects of hormone
      replacement therapy (HRT) for cardiovascular, osteoporosis-related, and cancer
      diseases. There is concern that risk estimates may be confounded by complex
      mechanisms of selection with regard to important risk determinants. In this
      study, we tested the hypothesis that baseline characteristics of women vary with
      exposure characteristics, i.e., the choices of complying with prescriptions,
      using different compounds and regimens, and continuing intake long-term. We
      analyzed the prevalence of relevant risk factors and their relationships to
      characteristics of exposure among 11,211 Swedish women who had received
      prescription for HRT. Associations were studied through logistic regression, with
      comparisons of women with ever-use versus non-compliance, long-term (73+ months)
      versus short-term use (1-72 months), intake of conjugated estrogens versus
      estradiol compounds, and intake of estrogens only versus estrogens combined with
      progestins, respectively. We found that women denying intake of using HRT short
      term had higher parity, earlier age at first birth and a lower prevalence of
      hysterectomy or oophorectomy than those complying or exposed long-term. A high
      level of education was associated with compliance and long-term exposure, and
      heavy physical exercise and high intake of food fibers were associated with
      compliance. Climacteric symptoms were associated with compliance, long-term
      intake and use of conjugated estrogens, whereas a history of oral contraceptive
      intake was associated with use of estrogens alone without progestins. We conclude
      that selection biases in studies of HRT effects are important and complex in that
      they may vary with the reported exposure. Our findings are important, as they
      point to the need for improved methods for measuring, in particular, factors
      linked to lifestyle and health behavior, in order to account more fully for
      confounding in the analyses of risk relationships.

PMID- 9180655
TI  - Validation of pharmacy records in drug exposure assessment.
AB  - The validity of drug exposure measurement based on pharmacy records was
      investigated taking into account completeness of data, drug compliance, and
      different methods of drug exposure measurement in pharmacy records. Data on
      prescription drug use were collected from home inventories and community
      pharmacies in a survey on drug use and compliance in 115 elderly people. To
      compare drug exposure in pharmacy records with exposure in the home inventory,
      three different methods for exposure measurement in pharmacy records were used.
      Two employed a fixed time window of 30 and 90 days, respectively, and the third
      method was based on the calculated duration of use of a prescription ("legend
      time"). Drug exposure in the home inventory was taken as the gold standard and
      sensitivity, specificity, and positive predictive values of the different methods
      were calculated for the most frequently used drugs and drug categories. The
      specificity and positive predictive value of all three methods was generally high
      (0.93-1.00 and 0.67-1.00, respectively). The 90-day fixed method and the legend
      time method generally showed high sensitivity (range: 0.67-1.00 and 0.63-0.83,
      respectively) for drugs that were used on a chronic basis, while the 30-day fixed
      method had poor sensitivity (range: 0.29-0.69). Drugs that were used according to
      the home inventory but not according to the pharmacy records methods could be
      almost completely retrieved in the pharmacy records of a one-year period showing
      that these records were virtually complete with regard to prescription drugs. We
      conclude that computerized pharmacy records can be a reliable source of the true
      drug exposure as estimated in a home inventory, when adequate attention is paid
      to the definition of the exposure time-window and when these records are
      comprehensive with regard to prescription drugs.

PMID- 9180656
TI  - "Conflicts of interest" and "political science".

PMID- 9180657
TI  - Comment on physical activity.

PMID- 9180658
TI  - The impact of aging and chronic disease on use of hospital and outpatient
      services in a large HMO: 1971-1991.
AB  - OBJECTIVES: To examine overall and diagnosis-specific trends in the use of
      inpatient and outpatient medical services (1970-1988) among older members of a
      large HMO. DESIGN: Two cohorts of approximately 3000 persons aged 65 or older in
      1971 and 1980 were compared for hospital and outpatient utilization during 9-year
      follow-up periods (1971-79 and 1980-88). All subjects were evaluated for vital
      status throughout the follow-up period as well. PARTICIPANTS: All 6057 subjects
      were members of the Northern California Kaiser Permanente Medical Care Program in
      1971 or 1980. The study sample was sex-age stratified (65-69,70-79,80+) at
      baseline. MEASUREMENTS: Data on demographics, outpatient health services
      utilization, categories of outpatient utilization and disease diagnoses were
      obtained from membership lists or medical chart review; inpatient utilization,
      including admitting and discharge diagnosis, length of stay, and number of
      hospital days was assessed from computerized hospitalization records. RESULTS:
      Hospital discharge rates (sex-age adjusted) increased by 12% between cohorts,
      with the largest increases at the oldest ages. There was a 25% increase among
      women and a 9% increase among men. Length of stay decreased by 20%.
      Hospitalization for ischemic heart disease decreased by 17%. Congestive heart
      failure (CHF) discharge rates (sex-age adjusted) were 92% higher in the 1980-88
      cohort. For diagnoses related to nursing home institutionalization and frailty,
      discharge rates were significantly higher in the 1980-88 cohort: pneumonia
      (+34%), urinary tract infections (+104%), dehydration (+110%), osteoarthritis
      (+64%), syncope (+246%), leg cellulitis (+70%). In-hospital survival improved,
      but overall percent of readmissions also increased by 4%; readmissions for CHF
      increased by 13% and those for conditions of frailty by 120%. Overall outpatient
      visits increased by 17%. Use of laboratory tests (+57%) and outpatient surgeries
      (+99%) increased for all age strata in 1980-88 compared with 1971-79.
      CONCLUSIONS: While overall outpatient and inpatient utilization has largely
      decreased over the past 30 years, as a result of economic factors and improved
      treatments for some major diseases, there has been an increase in utilization
      among older people. Hospitalization for diagnoses associated with end-stage
      cardiovascular disease (CHF), musculoskeletal disease, frailty and iatrogenic
      aspects of institutionalization are clearly increasing substantially. The largest
      impact of aging on health care may be the result of institutionalization and its
      sequelae. Improved treatment for cardiovascular disease may also be leading to
      increased utilization at later stages in the disease process.

PMID- 9180659
TI  - A clinical trial to reduce restraints in nursing homes.
AB  - OBJECTIVE: To investigate the relative effects of two experimental interventions
      on the use of physical restraints. DESIGN: Prospective 12-month clinical trial in
      which three nursing homes were randomly assigned to restraint education (RE),
      restraint education-with-consultation (REC), or control (C). SETTING: Three
      voluntary nursing homes in the Philadelphia area providing both skilled and
      intermediate care. PARTICIPANTS: A total of 643 nursing home residents over the
      age of 60 were enrolled at baseline, and 463 remained to completion (1 year).
      INTERVENTIONS: Both RE and REC homes received intensive education by a masters
      prepared gerontologic nurse to increase staff awareness of restraint hazards and
      knowledge about assessing and managing resident behaviors likely to lead to use
      of restraints. In addition, the REC home received 12 hours per week of unit-based
      nursing consultation to facilitate restraint reduction in residents with more
      complex conditions. MEASUREMENTS: Restraint status was observed systematically at
      baseline, immediately after the 6-month intervention, and again at 9 and 12
      months. Staff levels, psychoactive drug use, and injuries were also determined.
      RESULTS: Compared with baseline, the REC home had a statistically significant
      reduction in restraint prevalence, whereas RE and C homes did not. At 9 months (3
      months post-intervention), absolute decline in the percents restrained were 7%
      RE, 7% C, and 20% REC; at 12 months (6 months post-intervention) declines were 4%
      RE, 6% C, and 18% REC. However, relative to baseline, these declines represent an
      average reduction in restraint use of 23% RE, 11% C, and 56% REC. The differences
      in changes over time were consistently significant (P = .01), whether considering
      survivors or those present at each time point, and also when controlling for
      differences between groups at baseline. Further, given any change in restraint
      use, REC-residents were between 25% and 40% more likely than either RE or C
      residents to experience decreased restraint use. Results were achieved without
      increased staff, psychoactive drugs, or serious fall-related injuries.
      CONCLUSION: A 6-month-long educational program combined with unit-based, resident
      centered consultation can reduce use of physical restraints in nursing homes
      effectively and safely. Whether extending the intervention will achieve greater
      reduction is not known from these results.

PMID- 9180660
TI  - Correlates of kyphosis in older women. The Fracture Intervention Trial Research
      Group.
AB  - OBJECTIVE: To determine the association between kyphosis (degree of forward
      curvature of the thoracic spine) and measures of spinal osteoporosis (height loss
      and vertebral fractures) and chronic back pain and disability in older women.
      DESIGN: A cross-sectional study. SETTING: Eleven clinical centers in the United
      States. PARTICIPANTS: A total of 6439 community-dwelling osteoporotic women aged
      55-80 enrolled in the Fracture Intervention Trial (FIT), a multicenter clinical
      trial of alendronate. MEASUREMENTS: Thoracic curvature was measured at baseline
      using a Debreuner Kyphometer. Height loss was determined by subtracting current
      height measured with a Harpenden stadiometer from self-reported height at age 25.
      Vertebral fractures were defined by morphometry and semiquantitative reading of
      lateral thoracic and lumbar spine radiographs, and chronic back pain and back
      related disability were assessed by questionnaire. RESULTS: After adjustment for
      age, a 15 degrees increase in kyphosis was associated with losing more than 4 cm
      of height (OR, 1.88; 95% CI, 1.79-2.03) and having a vertebral fracture (OR,
      1.57; 95% CI, 1.46-1.69). Kyphosis was more strongly related to thoracic
      fractures than to lumbar fractures, and kyphosis was most prominent in women with
      multiple thoracic wedge fractures. Kyphosis was also associated with upper back
      pain (OR per 15 degrees increase, 1.62; 95% CI 1.47-1.79) and middle back pain
      (OR per 15 degrees increase, 1.24; 95% CI 1.12-1.36), but it was not related to
      lower back pain (OR per 15 degrees increase, 0.98; 95% CI 0.90-1.05). Women with
      greater degrees of kyphosis were only slightly more likely to report back-related
      disability (OR per 15 degrees increase, 1.18; 95% CI 1.03-1.35) and poorer health
      status (OR per 15 degrees increase, 1.19; 95% CI 1.03-1.37). CONCLUSIONS: Older
      women with greater degrees of kyphosis are likely to have other manifestations of
      spinal osteoporosis such as height loss and thoracic fractures and to suffer
      chronic upper and middle back pain. Measurement of kyphosis may be useful in
      assessing the severity of spinal osteoporosis.

PMID- 9180661
TI  - Older Medicare enrolees' choices for insured services.
AB  - OBJECTIVES: The Medicare Trust Fund is expected to be bankrupt in the next
      decade, thus threatening the viability of the Medicare Program. We have
      ascertained what Medicare enrollees' priorities for insured services would be,
      and why, if it were fiscally necessary to limit Medicare benefits to maintain the
      viability of the Program. DESIGN: A cross-sectional survey using anonymous,
      inperson interviews and an innovative instrument to elicit choices. SETTING:
      General Internal Medicine outpatient clinic at a university teaching hospital.
      PARTICIPANTS: One hundred five adults, 65 years of age and older, who had primary
      care physician visits between July and September 1995. MEASUREMENTS: Desire to
      personally select insurance benefits, insurance benefit choices, and the reasons
      for selection or rejection of benefits. RESULTS: Subjects of various educational
      and economic backgrounds were able to carry out the selection process with
      relative case, and four-fifths of respondents preferred to make their own choices
      about insured services. The most frequently selected services were
      hospitalization, outpatient care, prescription drugs, eye care, and home care, in
      descending order. Subjects selected 52 different combinations of services. Only
      2% of respondents picked the current Medicare service package. The reasons given
      for selection varied by service; cost and current or anticipated need for a
      service were the most frequently cited forces driving the choices made.
      CONCLUSION: These data suggest that Medicare enrollees prefer some element of
      choice about their health insurance coverage. Their choices vary widely and
      differ from the current Medicare package.

PMID- 9180662
TI  - Prevalence of undiagnosed non-insulin-dependent diabetes mellitus and impaired
      glucose tolerance in a cohort of older persons with hypertension.
AB  - OBJECTIVE: To determine the prevalence of undiagnosed non-insulin-dependent
      diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in a cohort of
      older persons with hypertension. To examine the usefulness of screening for NIDDM
      in this study population. DESIGN: Cross-sectional study. SETTING: University of
      Tennessee, Memphis and the General Clinical Research Center (GCRC). PATIENTS:
      Ninety-five participants in the Trial of Nonpharmacologic Interventions in the
      Elderly (TONE) study who agreed to participate in an ancillary study.
      MEASUREMENTS: A standard oral glucose tolerance test (OGTT) with insulin and C
      peptide levels was performed before the beginning of the TONE intervention.
      RESULTS: In this cohort, 43 participants (45.3%) had normal glucose tolerance
      (NGT), 41 (43.2%) had IGT, and 11 (11.6%) had undiagnosed NIDDM. The positive
      predictive value for NIDDM of a fasting glucose > or = 115 mg/dL in our
      participants was 57%. Hyperinsulinemia occurred in only one participant, a
      subject in the IGT group. CONCLUSIONS: Our data demonstrate that undiagnosed
      NIDDM is common in our cohort of older persons who are being treated for
      essential hypertension and that impaired glucose tolerance may be more common
      than in the general population of the same age. Further, our data show that the
      vast majority of this older, obese, hypertensive cohort did not have fasting
      hyperinsulinemia. We also infer that a fasting glucose alone has a low positive
      predictive value for screening of NIDDM in our older cohort. As the prevalence of
      NIDDM and impaired glucose tolerance in older hypertensive patients in the
      general population is unknown, we believe that further investigation is needed to
      characterize the relationship of hypertension, glycemic status, and
      hyperinsulinemia in the general population.

PMID- 9180663
TI  - Clinical correlates of low blood pressure in very old people: the importance of
      cognitive impairment.
AB  - OBJECTIVE: To identify the medical conditions associated with low blood pressure
      in very old people. DESIGN: A population-based, cross-sectional study. SETTING:
      Two neighboring communities in Stockholm, Sweden. SUBJECTS: Participants were 319
      male and 1070 female participants, with the mean age of 85.0 years (SD = 5.8).
      MEASUREMENTS: Blood pressure recording, pulse rate counting, and Mini-Mental
      State Examination (MMSE) were conducted by trained nurses. Information on illness
      condition and activities of daily living (ADL) status was self-reported or
      gathered from proxy respondents. The computerized inpatient register system was
      also used for collecting the data of illness condition. Systolic pressure less
      than 130 mm Hg and diastolic pressure less than 70 mm Hg were defined as low
      systolic and diastolic pressure, respectively. MMSE score less than 24 was
      considered to indicate cognitive impairment. MAIN RESULTS: In multiple logistic
      regression analyses, low systolic pressure was related to slower pulse rate (< or
      = 60 per minute), heart failure, ADL limitation, and cognitive impairment, and
      low diastolic pressure was related to increasing age, slower pulse rate, cardiac
      dysrhythmia, ADL limitation, and cognitive impairment. People with diabetes
      mellitus were less likely to be in the low systolic pressure group. 34.9% of the
      prevalence of low systolic pressure, and 17.9% of the prevalence of low diastolic
      pressure was associated with cognitive impairment. CONCLUSIONS: Low blood
      pressure in the very old may be associated with poor functional status, cardiac
      insufficiency and, more importantly, cognitive impairment. It would be expected
      that low blood pressure is associated with increased mortality in this age group.

PMID- 9180664
TI  - The "common cold" in frail older persons: impact of rhinovirus and coronavirus in
      a senior daycare center.
AB  - OBJECTIVE: To evaluate the incidence and impact of rhinovirus and coronavirus
      infections in older persons attending daycare. DESIGN: Prospective descriptive
      study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS:
      Frail older persons and staff members of the daycare centers who developed signs
      or symptoms of an acute respiratory illness. MEASUREMENTS: Demographic, medical,
      and physical findings were recorded on subjects at baseline and during
      respiratory illness. Nasopharyngeal specimens for viral culture as well as acute
      and convalescent sera for coronavirus 229E enzyme immunoassay (EIA) were obtained
      for all illnesses. RESULTS: During the 44 months of study, 352 older persons
      experienced 522 illnesses. Thirty-five (7%) of 522 cultures were positive for
      rhinovirus and 37 (8%) of 451 serologies were positive for coronavirus 229E
      infection. The clinical syndromes associated with rhinovirus and coronavirus
      infection were similar and characterized by nasal congestion, cough, and
      constitutional symptoms. No patient died or was hospitalized, but approximately
      50% had evidence of lower respiratory tract involvement. The average illness
      lasted 14 days. During the same period, 113 staff developed 338 respiratory
      illnesses. Eight percent were identified as coronavirus and 9% as rhinovirus.
      Cough, sputum production, and constitutional symptoms were significantly more
      common among older persons. CONCLUSIONS: Rhinovirus and coronavirus 229E are
      common causes of moderately debilitating acute respiratory illnesses among older
      persons attending daycare.

PMID- 9180665
TI  - Blood pressure reduction and tolerability of felodipine ER in older and younger
      hypertensive patients. The Felodipine ER in the Elderly versus Young Working
      Group.
AB  - OBJECTIVE: To evaluate and compare blood pressure reduction and tolerability of
      felodipine ER (extended-release), in younger and older patients. DESIGN: A
      multicenter, double-blind, placebo-controlled, parallel group study. SETTING:
      Nineteen study sites; approximately half of the sites were at academic medical
      centers and half were in private primary care practices. Patients were non
      hospitalized and free-living. PATIENTS: There were 243 younger (< or = 61 years)
      and older (> or = 64 years) patients, age range 26 to 83, with sitting diastolic
      blood pressure (SDBP) of 95-115 mm Hg (higher stage 1 to lower stage 3) on
      placebo. Patients volunteered for the study. INTERVENTIONS: After a 2 to 4 week,
      single-blind, placebo baseline period, patients with SDBP of 95-115 mm Hg were
      randomized to treatment with felodipine ER 2.5 mg qd or placebo at a ratio of
      3:1, felodipine:placebo. The dose of felodipine ER was increased to 5 mg qd after
      3 weeks and to 10 mg qd after 6 weeks if the SDBP was greater than 90 mm Hg.
      MEASUREMENTS: The main outcome measure was change in SDBP. Secondary Outcome
      measures were change in sitting systolic blood pressure (SSBP) and percent of
      responders, defined as SDBP less than 90 mm Hg or a > or = 10 mm Hg reduction.
      Other measurements included heart rate, weight, routine laboratory values, and
      self-reported adverse events. RESULTS: By Week 9, felodipine ER reduced blood
      pressure in the older subjects (n = 77) by 13/12 mm Hg; in the younger patients,
      (n = 102), the reduction was 12/8 mm Hg. All reductions were significantly
      different from placebo (P < or = .003). The reduction in diastolic, but not
      systolic, blood pressure was significantly greater in the older than in the
      younger patients (P = .004 and P = .188, respectively). The percentage of
      patients reporting a clinical adverse experience was similar for felodipine ER
      and placebo treatment groups. The incidence of side effects was similar between
      old and young patients. Discontinuation occurred in 9% of the felodipine-treated
      patients and 19% of the placebo-treated patients. Older patients required lower
      doses of felodipine ER to achieve equivalent blood pressure control. CONCLUSIONS:
      Felodipine ER is effective in lowering blood pressure and is well tolerated in
      both young and old people.

PMID- 9180666
TI  - The relation between antioxidants and memory performance in the old and very old.
AB  - OBJECTIVES: Aging processes, and among them brain aging, are thought to be
      associated with free radical action. It is hypothesized that plasma antioxidant
      vitamin levels correlate with cognitive performance in healthy older subjects.
      DESIGN: Longitudinal and cross-sectional comparisons. SETTING: The city of Basle,
      considered representative of the older urban population in Switzerland.
      PARTICIPANTS: A total of 442 subjects aged 65 to 94 years (mean: 75 years; 312
      male, 132 female) was selected from a random sample. MEASUREMENTS: In 1993,
      participants were tested for memory, and plasma vitamin levels were measured for
      the three antioxidants alpha-tocopherol, ascorbic acid, and beta-carotene. These
      vitamin parameters, measured previously in 1971 in the same sample, were
      integrated in our analyses. In addition, plasma cholesterol, ferritin, and
      systolic blood pressure were taken into account. Memory variables were priming,
      working-memory, free recall, recognition and the WAIS-R vocabulary test (semantic
      memory). RESULTS: Correlations showed significant stability of the plasma
      antioxidants over the time lag of 22 years (alpha-tocopherol: r = .47, P < or =
      .001; beta-carotene: r = .43, P < .001; ascorbic acid: r = .22, P < .001). Free
      recall, recognition, and vocabulary (but not priming and working-memory)
      correlated significantly with ascorbic acid and beta-carotene in the cross
      sectional 1993 data as well as in the longitudinal 1971-1993 analysis. These two
      antioxidants remained significant predictors, especially of semantic memory,
      after controlling for possible confounding variables like age, education, and
      gender using multiple regression analyses and ANOVAs. CONCLUSION: Among people
      aged 65 and older, higher ascorbic acid and beta-carotene plasma level are
      associated with better memory performance. These results indicate the important
      role played by antioxidants in brain aging and may have implications for
      prevention of progressive cognitive impairments.

PMID- 9180667
TI  - How older patient preferences are influenced by consideration of future health
      outcomes.
AB  - OBJECTIVE: To determine patients' willingness to accept intubation and
      ventilatory support (IVS) when the best outcome available is a state involving
      both cognitive and physical/behavioral deficits. DESIGN: Structured interviews
      with patients seen consecutively in a continuity care general medicine clinic.
      SETTING: A university-based Department of Veterans Affairs Medical Center.
      SUBJECTS: A total of 113 patients (mean age = 67.3 years, age range 42-89; mean
      level of formal education = 12.6 years, range 2-24). MEASUREMENTS: Patients were
      asked to consider whether they would permit their physicians to intubate them and
      put them on ventilatory support when the best outcome to be expected was one of
      three future health care states, presented in the following order: State 1, where
      their mental and physical state of recovery would be exactly like their current
      mental and physical states at the time of their visit to the general medicine
      clinic (the patient's current baseline mental and physical functioning); State 2,
      involving cognitive compromise; State 3, involving both cognitive and
      physical/behavioral compromise. RESULTS: One patient refused IVS on State 1;
      20.4% (23/113) of patients refused IVS on State 2; 23.0% (26/113) refused IVS on
      State 3; and 49.6% (56/113) reported they would accept IVS resulting in all three
      states. Six of 113 patients (5.3%) reported they would leave the decision up to
      their physician beginning with State 1 and continuing through State 3. One
      patient reported that he would leave the decision (State 1 through State 3) up to
      his wife. A reported history of stroke is related to patients' expressed dislike
      of IVS that would leave them with residual deficits. CONCLUSION: The results
      suggest that a substantial number of our older male veteran population would
      prefer intubation and ventilatory support if presented with a situation in which
      the best outcome that a physician could offer them was cognitive, physical, and
      behavioral dysfunction. These results also indicate that those patients who have
      had a stroke seem to be less inclined to accept IVS in more severe outcomes
      states.

PMID- 9180668
TI  - Do acute care for elders units increase hospital costs? A cost analysis using the
      hospital perspective.
AB  - OBJECTIVE: To compare the hospital costs of caring for medical patients on a
      special unit designed to help older people maintain or achieve independence in
      self-care activities with the costs of usual care. DESIGN: A randomized
      controlled study. PARTICIPANTS: A total of 650 medical patients (mean age 80
      years, 67% women, 41% nonwhite) assigned randomly to either the intervention unit
      (n = 326) or usual care (n = 324). MEASURES: The hospital's resource-based cost
      of caring for patients was determined from the hospital's cost-accounting system.
      The cost of the intervention program was estimated and included in the
      intervention patients' total hospital cost. RESULTS: The development and
      maintenance costs of the intervention added $38.43 per bed day to the
      intervention patients' hospital costs. As a result, the cost per day to the
      hospital was slightly higher in the intervention patients than in the control
      patients ($876 vs $847, P = .076). However, the average length of stay was
      shorter for intervention patients (7.5 vs 8.4 days, P = .449). As a result, the
      hospital's total cost to care for intervention patients was not greater than
      caring for usual-care patients ($6608 in intervention patients vs $7240 in
      control patients, P = .926). Sensitivity analysis demonstrated that the cost of
      the intervention program would need to be 220% greater than estimated before
      intervention patients would be more expensive then control patients. There were
      no examined subgroups of patients in whom care on the intervention unit was
      significantly more expensive than care on the usual-care unit. Ninety-day nursing
      home use was lower in intervention than control patients (24.1% vs 32.3%, P =
      .034). Ninety-day readmission rates (36.7% vs 41.1%, P = .283) and caregiver
      strain scores (3.3 vs. 2.7, P = .280) were similar. CONCLUSION: Caring for
      patients on an intervention ward designed to improve functional outcomes in older
      patients was not more expensive to the hospital than caring for patients on a
      usual-care ward even though the intervention ward required a commitment of
      hospital resources.

PMID- 9180669
TI  - One-leg balance is an important predictor of injurious falls in older persons.
AB  - OBJECTIVE: To test the hypothesis that one-leg balance is a significant predictor
      of falls and injurious falls. DESIGN: Analysis of data from a longitudinal cohort
      study. SUBJECTS: Healthy, community-living volunteers older than age 60 enrolled
      in the Albuquerque Falls Study and followed for 3 years (N = 316; mean age 73
      years). MAIN OUTCOME MEASURES: Falls and injurious falls detected via reports
      every other month. INDEPENDENT VARIABLES: Baseline measures of demographics,
      history, physical examination, Iowa Self Assessment Inventory, balance and gait
      assessment, and one-leg balance (ability to stand unassisted for 5 seconds on one
      leg). RESULTS: At baseline, 84.5% of subjects could perform one-leg balance.
      (Impairment was associated with older age and gait abnormalities.) Over the 3
      year follow-up, 71% experienced a fall and 22% an injurious fall. The only
      independent significant predictor of all falls using logistic regression was age
      greater than 73. However, impaired one-leg balance was the only significant
      independent predictor of injurious falls (relative risk: 2.13; 95% CI: 1.04,
      4.34; P = .03). CONCLUSION: One-leg balance appears to be a significant and easy
      to-administer predictor of injurious falls, but not of all falls. In our study,
      it was the strongest individual predictor. However, no single factor seems to be
      accurate enough to be relied on as a sole predictor of fall risk or fall injury
      risk because so many diverse factors are involved in falling.

PMID- 9180670
TI  - Chronic medical conditions and risk of fall injury events at home in older
      adults.
AB  - OBJECTIVE: To evaluate the association between selected chronic medical
      conditions (CMCs) and fall injury events at home among community-dwelling older
      persons. DESIGN: Population-based case-control study. SETTING: The general
      community. PARTICIPANTS: Persons aged 65 and older living at home, excluding
      those using a wheelchair; 467 cases and 691 control subjects were studied.
      MEASUREMENTS: The main independent variables were self-reported histories of 10
      CMCs: diabetes, high blood pressure, anemia, heart attack, Parkinson's disease,
      stroke, emphysema, cancer (other than skin), cataracts, and glaucoma. RESULTS:
      The final multivariate model included variables for age, sex, body mass,
      dependency in activities of daily living, current exercise (three or more times
      per week), mental status scores, and three CMCs. Persons with a history of stroke
      or anemia had an increased risk of a fall injury event: for stroke the adjusted
      odds ratio (aOR) equalled 1.7 (95% confidence interval (CI), 1.0-3.0); for anemia
      the aOR equalled 1.5 (95% CI, 1.0-2.2). Those with a history of high blood
      pressure had decreased risk (aOR = .7, 95% CI 0.5-0.9). CONCLUSIONS: Persons 65
      and older with a self-reported history of anemia or stroke are at increased risk
      of a fall injury event in the home, whereas those with a self-reported history of
      high blood pressure are at decreased risk.

PMID- 9180671
TI  - Abnormal exercise electrocardiograms in master athletes after three months of
      deconditioning.
AB  - OBJECTIVE: To determine the effects of 3 months of voluntary deconditioning on
      cardiac function in master athletes. DESIGN: A prospective study. SETTING:
      Research participants at the University of Maryland School of Medicine and Johns
      Hopkins Bayview Medical Center. PARTICIPANTS: Ten older (59 +/- 8 years, mean +/-
      SD), highly conditioned (maximal aerobic capacity VO2 max 50 +/- 5 mL/kg/min),
      aerobically trained athletes. MEASUREMENTS AND RESULTS: Three months after the
      cessation of training, three of the 10 athletes had unexpected, new, markedly
      asymptomatic, ischemic-appearing, exercise-induced ST-segment depression on their
      maximal exercise tests. After retraining, the ST-segment changes disappeared in
      two of the subjects, but it persisted, although at a higher work load, in one of
      the athletes. CONCLUSION: In three master athletes, voluntary cardiopulmonary
      deconditioning was associated with the development of new, asymptomatic, exercise
      induced ST-segment depression on exercise ECG. The mechanisms underlying these
      new ischemic-appearing ST-segment changes accompanying detraining and their
      clinical significance are not known and warrant further investigation.

PMID- 9180672
TI  - The effect of DHEAS on influenza vaccination in aging adults.
AB  - OBJECTIVE: To determine whether simultaneous administration of
      dehydroepiandrosterone sulfate (DHEAS) exhibits adjuvant activity in the immune
      response of aging humans by supplementing influenza vaccination with the maximum
      single dose of DHEAS that could be practically injected subcutaneously
      (approximately 7.5 mg). DESIGN: A randomized, double-blind, placebo-controlled
      trial of DHEAS injection with 1993-94 and 1994-95 influenza vaccine in older
      subjects. In addition, initial safety, tolerability, and control testing with
      1993-94 influenza vaccine was conducted in young subjects. SETTING: An urban
      primary care geriatrics clinic. PARTICIPANTS: Seventy-eight older adult
      volunteers (mean age 78.61 +/- 3.43 years, range 73-90 years) and 20 younger
      controls (< 40 years, means age 32.76 +/- 5.39 years) were recruited from clinic
      and community advertising. Subjects were free of disease or medication known to
      affect immune function. MEASUREMENTS: Immune responses to vaccine at 0, 2, and 4
      weeks were measured by vaccine antigen-induced lymphoproliferation in peripheral
      blood mononuclear cells (PBMC) and serum antibody response by hemagglutination
      inhibition (HI). RESULTS: The maximum DHEAS dose that could be practically
      administered subcutaneously was 7.5 mg. Baseline DHEAS levels were significantly
      lower in older adults (52.1 vs 236.4 micrograms/dL, P < .001). The 1993 old adult
      DHEAS group HI response tended to be higher for the H3N2 Beijing antigen but not
      for the H1N1 or B antigen. In subjects with HI titers less then 1:40 for the H3N2
      Beijing antigen (n = 29), the post-vaccination titer response tended to be higher
      among the 16 subjects who received DHEAS (P = .06). The peak response for the
      H3N2 antigen was associated with the initial DHEAS serum concentration in the
      DHEAS and placebo groups (R2 = .22, P = .04 and R2 = .21, P = .06, respectively).
      No significant differences were found for antibody responses to the H1N1 and B
      antigens or vaccine-antigen induced lymphoproliferation. CONCLUSION: A one-time
      supplemental dose of DHEAS with influenza vaccination appeared to enhance the
      specific HI antibody response to the 1993-94 H3N2 antigen in a small group of
      older adults. These findings were limited to those with lower prevaccination
      titers and lower DHEAS concentrations. Although clinical implications of these
      findings for influenza vaccine are uncertain, these results suggest additional
      detailed immunologic investigations on the role of DHEAS in the aging human
      immune response are warranted.

PMID- 9180673
TI  - Acute upper gastrointestinal hemorrhage in older people: a prospective study in
      two neighboring districts.
AB  - OBJECTIVE: To study the distribution of mucosal lesions and outcomes in older
      people with acute upper gastrointestinal hemorrhage (UGIH). DESIGN: Prospective
      case study. SETTING: Two neighboring district hospitals with similar admission
      policies. SUBJECTS: Consecutive patients aged 75 years or older admitted with
      hematemesis and/or melena during the study period. OUTCOME MEASURES: Length of
      hospital stay, mortality, surgical intervention, and transfusion requirements.
      RESULTS: A total of 109 patients were entered into the study. Of these, 106 (97%)
      underwent gastroscopy, and bleeding sites were identified in 98%. Upper gut
      malignancies were identified in eight patients, ulcerative esophagitis in 32,
      benign gastric ulcers in 24, and duodenal ulcers in 23 patients. Forty-seven
      percent had severe anemia on admission (Hb < 10 g/dL). Thirty-eight patients were
      referred for surgery, and eight were operated on, with one postoperative death.
      Six other patients died, five of whom had malignancies. The overall mortality of
      6% reduced to 2% if those with malignancy were excluded. The 92 patients
      discharged had a median hospital stay of 15 days (range 2-30). CONCLUSIONS: Older
      people with acute UGIH have advanced upper gut pathology with preponderance of
      esophageal lesions. Classical symptoms seem lacking, but mortality can be
      decreased despite adverse comorbid factors. Lower thresholds for endoscopy are
      advocated in older adults, and comparative studies of UGIH symptoms with younger
      patients are required.

PMID- 9180674
TI  - Viral hepatitis in older adults.
AB  - The objective of this paper is to review the epidemiology, manifestations,
      therapy, and prevention of viral hepatitis in older people and to discuss issues
      of prevention and management. In developed countries a significant portion of the
      adult population is not immune to Hepatitis A virus (HAV). Morbidity and
      mortality from HAV infection increases with age. A safe and effective hepatitis A
      vaccine is available and health authorities should consider immunization early in
      life and for healthy adults as well as for potential high risk groups such as
      nursing home residents. Acute hepatitis due to Hepatitis B virus (HBV) is rare in
      older people and is usually a mild disease. Most older patients with chronic HBV
      infection who suffer from advanced liver disease have no evidence of ongoing
      viral replication. Therefore, they are not candidates for interferon therapy.
      Those with evidence of ongoing viral replication and compensated liver disease
      should be offered interferon or be included in clinical trials with new antiviral
      drugs such as lamivudine. Since the response rate to hepatitis B vaccination
      decreases with age, developing vaccines with greater immunogenicity is crucial.
      Hepatitis C virus (HCV) is the most frequent cause of acute viral hepatitis in
      older people. Acute hepatitis C is usually a mild disease in this age group.
      Because many older patients with chronic HCV infection have compensated liver
      disease, they could benefit from antiviral therapy. In light of the low response
      rate to interferon in older patients with chronic hepatitis C and the side
      effects of the drug, interferon therapy should be reserved for those with the
      best chance of response. "Combination" antiviral therapy should be on trial for
      older patients with chronic HCV infection who do not respond to interferon. The
      recently discovered RNA virus, Hepatitis G (HGV), has been associated with liver
      disease in older people. It's role in the pathogenesis of liver injury remains to
      be elucidated.

PMID- 9180675
TI  - A geriatric consultation team in the emergency department.
AB  - BACKGROUND: The proportion and absolute number of older patients presenting to
      emergency departments (EDs) are increasing. Older ED patients tend to have
      multiple medical and psychosocial problems that make their care in the ED
      problematic. Despite this, there have been no previous descriptions of geriatric
      ED consultative services. SETTING: The Sir Mortimer B. Davis Jewish General
      Hospital is a 628-bed tertiary care McGill University teaching hospital. It
      serves a population of about 160,000, of which 23% are aged 65 and older. In
      response to the special needs of this group, the Division of Geriatric Medicine
      at the Jewish General Hospital has developed, among its clinical and teaching
      services, an ED consultation team. PROGRAM DESCRIPTION: The consultation team is
      composed of a geriatrician, a full-time nurse clinician, and part-time physical
      and occupational therapists. Consultations are received from referring, primarily
      Ed physicians and encompass all aspects of medical and psychosocial issues.
      Geriatric assessment is geared toward decision making for rapid disposition:
      discharge home or admission to acute geriatrics ward or other services. Thus, the
      service functions as a gatekeeper for admission to the acute geriatrics ward, as
      well as coordinating geriatric follow-up both in-hospital (for patients admitted
      to other services) and in the community (for patients discharged home), via the
      outpatient geriatric clinic, home visits, or linkage to other community
      resources.

PMID- 9180676
TI  - Why is health care use rising if morbidity is being compressed?

PMID- 9180677
TI  - Dealing from the same deck.

PMID- 9180678
TI  - Physical restraint: not fit for woman, man, or beast.

PMID- 9180679
TI  - Pre-dementia.

PMID- 9180680
TI  - The relation of callosal atrophy and interhemispheric transfer of information: a
      comment on Janowsky et al. (1996)

PMID- 9180681
TI  - Delirium, dementia and brain reserve.

PMID- 9180682
TI  - Holotranscobalamin II levels in plasma are related to dementia in older people.

PMID- 9180683
TI  - Bedrail use.

PMID- 9180684
TI  - Driving performance in older in-patients.

PMID- 9180685
TI  - White cell scanning in a fever of unknown origin in an older woman.

PMID- 9180686
TI  - A novel homologue of the prokaryotic htrA gene is differentially expressed in the
      alga Haematococcus pluvialis following stress.
AB  - The alga Haematococcus pluvialis is able to respond to environmental stress by
      changing from the motile, vegetative green cell form to red stationary
      aplanospores. This differentiation program is accompanied by dramatic
      morphological changes that must result, at least in part, from differential gene
      expression. To begin to identify genes that are differentially expressed as a
      response to stress, we applied the differential display technique to identify and
      isolate differentially expressed RNA sequences. Here we report on the isolation
      and characterization of one such RNA sequence that codes for Haematococcus htrA,
      a member of a heat shock serine protease family previously described only in
      prokaryotes. Interestingly, database searches of mouse and human cDNA sequences
      showed that a previously unreported homologue is also found in a number of
      tissues. htrA mRNA was not detectable in vegetative cells, but was found at high
      levels in developing aplanospores. Evidence presented suggests that RNA
      transcripts encoding this protein are differentially spliced, and that the
      different splice products are differentially expressed during the developmental
      process. These experiments provide the groundwork upon which the developmental
      program of H. pluvialis can be investigated. In addition, they indicate that the
      htrA family of heat shock serine proteases may play an important role in stress
      response in higher organisms as well as in bacteria.

PMID- 9180687
TI  - Functional dissection of a cell-division inhibitor, SulA, of Escherichia coli and
      its negative regulation by Lon.
AB  - SulA is induced in Escherichia coli by the SOS response and inhibits cell
      division through interaction with FtsZ. To determine which region of SulA is
      essential for the inhibition of cell division, we constructed a series of N
      terminal and C-terminal deletions of SulA and a series of alanine substitution
      mutants. Arginine at position 62, leucine at 67, tryptophan at 77 and lysine at
      87, in the central region of SulA, were all essential for the inhibitory
      activity. Residues 3-27 and the C-terminal 21 residues were dispensable for the
      activity. The mutant protein lacking N-terminal residues 3-47 was inactive, as
      was that lacking the C-terminal 34 residues. C-terminal deletions of 8 and 21
      residues increased the growth-inhibiting activity in lon+ cells, but not in lon-
      cells. The wild-type and mutant SulA proteins were isolated in a form fused to E.
      coli maltose-binding protein, and tested in vitro for sensitivity to Lon
      protease. Lon degraded wild-type SulA and a deletion mutant lacking the N
      terminal 93 amino acids, but did not degrade the derivative lacking 21 residues
      at the C-terminus. Furthermore, the wild-type SulA and the N-terminal deletion
      mutant formed a stable complex with Lon, while the C-terminal deletion did not.
      MBP fused to the C-terminal 20 residues of SulA formed a stable complex with, but
      was not degraded by Lon. When LacZ protein was fused at its C-terminus to 8 or 20
      amin acid residues from the C-terminal region of SulA the protein was stable in
      lon+ cells. These results indicate that the C-terminal 20 residues of SulA permit
      recognition by, and complex formation with, Lon, and are necessary, but not
      sufficient, for degradation by Lon.

PMID- 9180689
TI  - Partial purification of mitochondrial ribosomes from broad bean and
      identification of proteins encoded by the mitochondrial genome.
AB  - An approach towards the identification at the protein level of the ribosomal
      proteins encoded by the mitochondrial genome of broad bean (Vicia faba) has been
      developed. After Triton X-100 treatment of isolated mitochondria, a fraction
      enriched in mitochondrial ribosomes was obtained by successive centrifugation,
      first onto a sucrose cushion, and then in a sucrose gradient. Mitochondrial
      translation products were labelled in isolated mitochondria with [35S]methionine
      and added to the enriched mitochondrial ribosomal proteins before separation by
      two-dimensional gel electrophoresis. Six spots, identified both by Coomassie blue
      staining and autoradiography, were analysed by protein micro-sequencing. Two of
      these were shown to correspond to ribosomal proteins S10 and S12. We conclude
      that these two proteins are encoded by the mitochondrial genome of broad bean and
      that the method described here can be used to identify other proteins encoded by
      the mitochondrial genome.

PMID- 9180688
TI  - Role of the coat protein-RNA interaction in the life cycle of bacteriophage MS2.
AB  - The coat protein of the RNA bacteriophage MS2 interacts with viral RNA to
      translationally repress replicase synthesis. This protein-RNA interaction is also
      thought to play a role in genome encapsidation. In this study the strength of the
      interaction was perturbed by constructing a recombinant genome containing a super
      repressing coat mutation. Because replicase synthesis is prematurely repressed,
      the mutant produces plaques about five orders of magnitude less efficiently than
      wild-type. The few plaques obtained are second-site revertants of the original
      coat mutation and fall into two categories. Those of the first type contain
      nucleotide substitutions within the translational operator that reduce or destroy
      its ability to bind coat protein, showing that this interaction is not necessary
      for genome encapsidation. Revertants of the second type are double mutants in
      which one substitution converts the coat initiator AUG to AUA and the other
      substitutes an A for the G normally present two nucleotides upstream of the coat
      start codon. The mutation of the coat protein gene AUG to AUA, by itself, reduces
      coat protein synthesis to a few percent of the wild-type level. The second
      substitution destabilizes the coat initiator stem-loop and restores coat protein
      synthesis to within a few fold of wild-type levels.

PMID- 9180690
TI  - A physical assay for meiotic recombination in Coprinus cinereus.
AB  - We have used the polymerase chain reaction (PCR) method to monitor meiotic
      recombination in the basidiomycete Coprinus cinereus. We used DNA-mediated
      transformation to recover strains with modifications of the trp1 locus. The
      modifications were designed to introduce unique PCR priming sites separated by a
      homologous 2.4 kb region in which crossing over could occur. We showed that
      exchange occurred in this region at the frequency expected for a typical region
      of this genome (2.4 kb should correspond to a genetic length of 0.08 cM). We also
      detected products resulting from crossing over in DNAs extracted from cells in
      meiotic prophase. The assay should be useful for monitoring exchange in mutants
      that cannot complete meiosis.

PMID- 9180691
TI  - Recombination of mitochondrial DNAs following transmission of mitochondria among
      incompatible strains of black Aspergilli.
AB  - Successful intra- and interspecific mitochondrial transfers were performed by
      polyethylene glycol (PEG)-induced protoplast fusion among incompatible strains
      belonging to the Aspergillus niger species aggregate. The mitochondrial DNAs
      (mtDNAs) of the strains examined were of three main types based on their
      restriction fragment length polymorphism (RFLP) profiles. mtDNA types 1 and 2
      correspond to A. niger and A. tubingensis species, respectively, while type 3 is
      represented by some Brazilian wild-type isolates (possibly a distinct species or
      subspecies). mtDNA types 1 and 2 could be further divided into several subgroups
      (1a-1e and 2a-2f). All these strains, representing different RFLP groups or
      subgroups, were fully incompatible with respect to nuclear complementation. The
      transfer experiments were carried out under selection pressure, using a
      mitochondrial oligomycin-resistant mutant of mtDNA type 1a as donor. Following
      fusion mitochondrial oligomycin-resistant progenies were recovered in the
      presence of oligomycin by selecting for the nuclear phenotypes of the oligomycin
      sensitive recipient strains. All attempted transfers were successful, and
      resulted in different varieties of resistant recombinant mitochondrial progenies
      at various frequencies. Within the group of strains of mtDNA type 1, the transfer
      of oligomycin-resistant mitochondria resulted in the appearance of a single
      recombinant type of RFLP profile in each case. The recombination events were more
      complex when the transfer of oligomycin resistance occurred between strains
      representing different species (mtDNA groups 1a-->2 and 1a-->3). A great variety
      of recombinant mtDNA RFLP profiles appeared. Explanation for this phenomenon are
      discussed on the basis of preliminary physical mapping data.

PMID- 9180692
TI  - Molecular analysis of hus1+, a fission yeast gene required for S-M and DNA damage
      checkpoints.
AB  - The structure of hus1+, a Schizosaccharomyces pombe gene required for S-M and DNA
      damage checkpoints, has been determined. Expression of hus1+ requires splicing of
      five exons, including a microexon that is only 13 nucleotides long. hus1+ is
      predicted to encode a 33 kDa protein with no similarity to sequences in any
      database, including the entire S. cerevisiae genome. Yeast strains disrupted for
      the hus1+ gene are viable but checkpoint-defective. Polyclonal antibodies were
      raised against bacterially expressed Hus1 protein, and used to study Hus1
      regulation. Hus1 protein levels are not affected by S-phase arrest, and are not
      altered by mutations in other checkpoint genes, suggesting that Hus1 is not
      regulated at the transcriptional or translational levels.

PMID- 9180693
TI  - Genetic evidence of a coupling role for the TraG protein family in bacterial
      conjugation.
AB  - The ability of conjugative plasmids from six different incompatibility groups to
      mobilize a set of mobilizable plasmids was examined. The mobilization frequencies
      of plasmids RSF1010, ColE1, ColE3, and CloDF13 varied over seven orders of
      magnitude, depending on the helper conjugative plasmid used. Mobilization of
      CloDF13 was unique in that it did not require TrwB, TraG or TraD (all members of
      the TraG family) for mobilization by R388, RP4 or F, respectively. CloDF13 itself
      codes for an essential mobilization protein (MobB) which is also a TraG homolog,
      only requiring a source of the genes for pilus formation. Besides, CloDF13 was
      mobilized efficiently by all conjugative plasmids, suggesting that TraG homologs
      are the primary determinants of the mobilization efficiency of a plasmid,
      interacting differentially with the various relaxosomes. Previous results
      indicated that TraG and TrwB were interchangeable for mobilization of RSF1010 and
      ColE1 by PILw (the pilus system of IncW plasmids) but TraG could not complement
      conjugation of trwB mutants, suggesting that additional interactions were taking
      place between TrwB and oriT(R388) that were not essential for mobilization. To
      further test this hypothesis, we analyzed the mobilization frequencies of ColE1
      and RSF1010 by the P, W, and F pili in the presence of alternative TraG homologs.
      The results obtained indicated that the frequency of mobilization was determined
      both by the particular TraG-like protein used and by the pilus system. Thus, TraG
      like proteins are not generally interchangeable for mobilization. Therefore we
      suggest that the factors that determine the frequencies of transfer of different
      MOB regions are the differential interactions of TrwB with pilus and relaxosome.

PMID- 9180694
TI  - Somatic variation during long-term subculturing of plant cells caused by
      insertion of a transposable element in a phenylalanine ammonia-lyase (PAL) gene.
AB  - We have identified a new En/Spm-like transposable element, Tdc1, in the 5'
      flanking region of a phenylalanine ammonia-lyase gene (gDcPAL1) that is normally
      induced by transferring cells of carrot suspension cultures to fresh liquid
      medium (transfer or dilution effect). The initial integration into gDcPAL1
      occurred more than 4 years after culture initiation. Tdc1 was first detected in
      gDcPAL1 genomic clones of a genomic library made from cells of the same cultured
      cell line 7 years after its initiation and thus following repeated subculturing.
      Twelve years after initiation, about 5-10% of the cells had Tdc1 inserted into
      the gDcPAL1 gene, indicating that Tdc1 insertion into gDcPAL1 occurred in one (or
      more) cell(s) during the first 4-7 years of subculturing. These mutant cells did
      not disappear during numerous passages; instead the proportion of cells having
      this Tdc1 inserted into gDcPAL1 has been increasing over the last 5 years. The
      promoter activity and the inducibility by transfer/dilution of the gDcPAL1 gene
      harboring Tdc1 is reduced relative to wild type. Finally, we show that insertion
      of a transposable element is one of the mechanisms that can cause variation of
      plant cell cultures during repeated subculture.

PMID- 9180696
TI  - A ras homologue of Neurospora crassa regulates morphology.
AB  - In order to study the role of signal transduction pathways in the regulation of
      morphology in Neurospora crassa, we cloned and characterized a ras homologue,
      termed NC-ras2. The predicted protein product of this gene is composed of 229
      amino acid residues and contains all the consensus sequences shared by the ras
      protein family. The gene is located in linkage group V. An NC-ras2 disruptant
      showed morphological characteristics very similar to those of the smco7 mutant,
      which also maps to linkage group V. Nucleotide sequence analysis revealed that
      the smco7 mutant harbored a single base deletion in the NC-ras2 gene, which is
      predicted to result in the truncation of the protein product. Introduction into
      the smco7 mutant of an NC-ras2 clone yielded stable transformants with a wild
      type phenotype. The smco7 mutant exhibited very slow hyphal growth and the rate
      of conidial formation was approximately one two-hundredth of wild type. The smco7
      mutation causes both the changes in the pattern of hyphal growth and the defects
      in cell wall synthesis. Both the diameter and the length of the apical
      compartment were shorter in the hyphae of the smco7 mutant. These results suggest
      that NC-ras2 is identical to smco7, and that the signal transduction pathway
      mediated by the NC-ras2 protein regulates the apical growth of hyphae, cell wall
      synthesis, and conidial formation in N. crassa.

PMID- 9180695
TI  - Multidrug resistance in Aspergillus nidulans involves novel ATP-binding cassette
      transporters.
AB  - Two single-copy genes, designated atrA and atrB (ATP-binding cassette transporter
      A and B), were cloned from the filamentous fungus Aspergillus nidulans and
      sequenced. Based on the presence of conserved motifs and on hydropathy analysis,
      the products encoded by atrA and atrB can be regarded as novel members of the ATP
      binding cassette (ABC) superfamily of membrane transporters. Both products share
      the same topology as the ABC transporters PDR5 and SNQ2 from Saccharomyces
      cerevisiae and CDR1 from Candida albicans, which are involved in multidrug
      resistance of these yeasts. Significant homology also occurs between the ATP
      binding cassettes of AtrA and AtrB, and those of mammalian ABC transporters (P
      glycoproteins). The transcription of atrA and, in particular, atrB in mycelium of
      A. nidulans is strongly enhanced by treatment with several drugs, including
      antibiotics, azole fungicides and plant defense toxins. The enhanced
      transcription is detectable within a few minutes after drug treatment and
      coincides with the beginning of energy-dependent drug efflux activity, reported
      previously in the fungus for azole fungicides. Transcription of the atr genes has
      been studied in a wild-type and in a series of isogenic strains carrying the imaA
      and/or imaB genes, which confer multidrug resistance to various toxic compounds
      such as the azole fungicide imazalil. atrB is constitutively transcribed at a low
      level in the wild-type and in strains carrying imaA or imaB. Imazalil treatment
      enhances transcription of atrB to a similar extent in all strains tested. atrA,
      unlike atrB, displays a relatively high level of constitutive expression in
      mutants carrying imaB. Imazalil enhances transcription of atrA more strongly in
      imaB mutants, suggesting that the imaB locus regulates atrA. Functional analysis
      demonstrated that cDNA of atrB can complement the drug hypersensitivity
      associated with PDR5 deficiency in S. cerevisiae.

PMID- 9180697
TI  - Indolepyruvate ferredoxin oxidoreductase from Pyrococcus sp. KOD1 possesses a
      mosaic structure showing features of various oxidoreductases.
AB  - Indolepyruvate ferredoxin oxidoreductase (IOR) catalyzes the oxidative
      decarboxylation of arylpyruvates. Gene cloning and sequencing analysis of the IOR
      gene from the hyperthermophilic archaeon Pyrococcus sp. KOD1 was performed. Two
      genes, iorA and iorB. encoding alpha and beta subunits of IOR were found to be
      tandemly arranged, which suggests that gene expression is translationally
      coupled. Sequence analysis showed the C-terminal region of the alpha subunit to
      have a typical ferredoxin-type [4Fe-4S] cluster motif (CXXCXXCXXCXXXCP), which is
      similar to that present in the delta subunits of other oxidoreductases such as
      pyruvate ferredoxin oxidoreductase (POR) and 2-ketoisovalerate ferredoxin
      oxidoreductase (VOR). We suggest that the alpha subunit of KOD1-IOR has a mosaic
      structure composed of features characteristic of the alpha, beta and delta
      subunits from POR and VOR. KOD1-IOR was overproduced in anaerobically incubated
      Escherichia coli cells and the crude enzyme was extracted under anaerobic
      conditions. The optimal temperature for activity of recombinant IOR was 70
      degrees C and the half-life of this enzyme in the presence of air was 15 min at
      25 degrees C.

PMID- 9180698
TI  - Autogenous and global control of the flagellar master operon, flhD, in Salmonella
      typhimurium.
AB  - Expression of the flagellar master operon, flhD, is known to be affected by
      growth conditions and by mutations in a variety of genes. In the present work,
      the transcriptional control of the Salmonella typhimurium flhD operon was
      investigated in various genetic backgrounds. First, we examined the effect of
      mutations in the global regulators cAMP-CRP, H-NS, OmpR and RpoS. Mutations in
      the cya, crp or hns gene reduced but did not eliminate flhD expression. However,
      expression was completely inhibited in the cya hns and crp hns double mutants.
      These results indicate that cAMP-CRP and H-NS independently activate the flhD
      operon and that maximal expression is attained in the presence of both
      regulators. On the other hand, the ompR and rpoS mutations did not affect either
      the motility phenotype or flhD expression. We next examined the expression of a
      chromosomal flhD-lac fusion gene in the presence of a plasmid carrying the wild
      type flhD operon. It was found that under this condition the chromosomal flhD
      operon was repressed or activated, depending on the intracellular activity of
      FliA, an alternative sigma factor specific for late flagellar operons. In the
      absence of FliA or in the presence of both FliA and its cognate anti-sigma factor
      FlgM, the flhD operon was autogenously repressed, whereas in the flgM mutant
      background it was autogenously activated in the presence of FliA. This
      autoregulation was still observed in the crp or hns mutant background, indicating
      that the autogenous control is achieved by a mechanism that is independent of the
      cAMP-CRP and H-NS regulatory pathways.

PMID- 9180700
TI  - Genetic organization and transposition properties of IS511.
AB  - IS511 is an endogenous insertion sequence (IS) of the bacterium Caulobacter
      crescentus strain CB15 and it is the first Caulobacter IS to be characterized at
      the molecular level. We determined the 1266-bp nucleotide sequence of IS511 and
      investigated its genetic organization, relationship to other ISs, and
      transposition properties. IS511 belongs to a distinct branch of the IS3 family
      that includes ISR1, IS476, and IS1222, based on nucleotide sequence similarity.
      The nucleotide sequence of IS511 encodes open reading frames (orfs) designated
      here as orfA and orfB, and their relative organization and amino acid sequences
      of the predicted protein products are very similar to those of orfAs and orfBs of
      other IS3 family members. Nuclease S1 protection assays identified an IS511 RNA,
      and its 5' end maps approximately 16 nucleotides upstream of orfA and about six
      nucleotides downstream of a sequence that is similar to the consensus sequence of
      C. crescentus housekeeping promoters. Evidence is presented that IS511 is capable
      of precise excision from the chromosome, and transposition from the chromosome to
      a plasmid. Transpositional insertions of IS511 occurred within sequences with a
      relatively high G + C content, and they were usually, but not always, flanked by
      a 4-bp direct repeat that matches a sequence at the site of insertion. We also
      determined the nucleotide sequence flanking the four endogenous IS511 elements
      that reside in the chromosome of C. crescentus. Our findings demonstrate that
      IS511 is a transposable IS that belongs to a branch of the IS3 family.

PMID- 9180699
TI  - Ectopic expression of sex-peptide in a variety of tissues in Drosophila females
      using the P[GAL4] enhancer-trap system.
AB  - Sex-peptide (SP), which is secreted by the accessory gland of Drosophila males,
      is transferred to the female during copulation, thereby reducing her sexual
      appetite (receptivity to males) and stimulating ovulation/oviposition. SP is
      known to be taken up into the hemolymph of mated females, but it is not clear
      whether there are two separate target tissues, for behavioral changes and
      ovulation or only one target for both responses. We have employed the GAL4-UAS
      system to express SP transgene constructs, both in different tissues and in
      different cellular components of virgin females. A cytoplasmic form of SP lacking
      a signal sequence did not evoke any responses, even when expressed ubiquitously.
      In contrast, a membrane-bound form of SP induced typical post-mating behavior,
      indicating that SP must be outside the cell in order to exert its biological
      effects. A total of 204 randomly selected P[GAL4] enhancer-trap lines were
      screened for their ability to induce SP responses in combination with the
      membrane-bound SP expressed under GAL4 control. Thirty-three lines were
      associated with both behavioral change and stimulated ovulation. No line was
      associated with only one of the two responses, implying that the SP target(s)
      mediating the two responses are either identical, very closely located, or
      present in two distinct tissues with a common set of genetic determinants.
      Western blot analysis of head, thorax, and abdominal extracts revealed that the
      biological activity was correlated with expression in the head fraction.

PMID- 9180701
TI  - The Brevibacterium albidum gene encoding the arginine tRNACCG complements the
      growth defect of an Escherichia coli strain carrying a thermosensitive mutation
      in the rnpA gene at the nonpermissive temperature.
AB  - The Escherichia coli rnpA gene encodes C5 protein, the protein component of RNase
      P. The rnpA49 mutation renders the C5 protein thermosensitive, which results in
      thermosensitivity of RNase P function. The chromosomal DNA region from
      Brevibacterium albidum that complements the rnpA49 mutation was analysed. The
      gene capable of complementing the growth defect of an rnpA49 mutant strain at
      nonpermissive temperature was identified as the gene for an arginine tRNA with
      anticodon CCG by a deletion analysis combined with complementation assays.
      Transcription of the arginine tRNA gene carried on a multicopy plasmid was
      correlated with the complementation of the rnpA49 mutation, indicating that the
      gene product is indeed responsible for complementation of the rnpA49 mutation.

PMID- 9180702
TI  - Gender-confirming facial surgery: considerations on the masculinity and
      femininity of faces.
AB  - While aesthetic facial surgery performed for reasons of undesired facial
      masculinity or femininity has had some attention in the literature, there is a
      lack of information on gender-confirming facial surgery as part of an overall
      surgical sex reassignment program. In this paper we try to capture some of the
      sex differences, respectively, of skeleton, musculature and other subcutaneous
      soft tissues, integument and frame of the face. From this, we come to a
      description of some general differences of facial appearance between the sexes.
      In restructuring the skeletal architecture and facial proportions to match the
      desired gender, these factors should be taken into account.

PMID- 9180703
TI  - Aesthetic analysis of the eyebrows.
AB  - Advances in surgical techniques and instrumentation have led to an increased
      popularity of brow-lifting procedures. However, because of patient variability
      and differing surgeon opinions, eyebrow aesthetics and thus surgical goals remain
      to be clearly defined. We performed an in-depth evaluation of current eyebrow
      aesthetics using two study groups. Popular fashion models were evaluated and
      compared with our own patient population. Important differences in eyebrow
      position and shape between these groups are delineated and the surgical
      implications defined. Criteria that contribute to the aesthetics of the eyebrow
      are reviewed, and guidelines to optimize surgical results and avoid potential
      complications are discussed.

PMID- 9180704
TI  - Ultrapulse carbon dioxide laser with CPG scanner for full-face resurfacing for
      rhytids, photoaging, and acne scars.
AB  - Eleven female patients are reported who underwent full-face resurfacing. Three
      patients were treated for cosmetic rhytids, five for residual acne scarring, and
      three for photoaging. There were no complications or side effects in this group
      of patients. Reepithelialization was achieved in an average of 9.3 days, and
      erythema disappeared in an average of 8.9 weeks. The UltraPulse carbon dioxide
      laser with computerized pattern generator (CPG) scanner allows a rapid, uniform
      laserbrasion. The sequence of the procedure involves close application of
      adjacent squares at 60 W, 200 to 300 ml, at moderate density. Skin preparation
      with Retin-A and bleaching agents is important for best wound healing.
      Postoperative wound care includes maintenance of a moist environment and Zovirax
      for herpes prophylaxis.

PMID- 9180706
TI  - Angle-splitting ostectomy for reducing the width of the lower face.
AB  - A patient with a large, squarish, or broad face who desires a small, round, or
      slender face can undergo mandibular contouring surgery to reduce the width of the
      lower face. The successful correction of a prominent mandibular angle by
      conventional angle ostectomy has been reported. However, in the majority of
      patients with a widened facial appearance, both the mandibular angle and part of
      the mandibular body anterior to it are protuberant laterally, so both must be
      resected. At our clinic, operations to reduce the width of the lower face have
      been performed on 76 patients (9 males and 67 females) during the last 5 years.
      Initially, we employed a combination of shaving of the lateral cortex and
      multistaged curved cuts of the mandibular angle. This operative technique,
      however, required a high level of skill and was time-consuming. A retrospective
      study of the results revealed the following additional drawbacks. The objective
      of this procedure is, in a sense, to create morphologically analogous mandibles
      in all patients, but on the one hand, the resulting relief of the mandibular
      angle tended to lack individuality, and on the other hand, the primary purpose of
      reducing the width of the lower face was not fully accomplished in some patients.
      With angle-splitting ostectomy, which we performed at a later date, however, the
      width of the lower face was efficiently reduced, producing a natural relief of
      the mandibular angle. If the surgeon in charge has precise anatomic knowledge and
      performs this on the basis of an accurate preoperative diagnosis and an operative
      plan, he or she will encounter no particular difficulties during the operation.
      There were no complications, such as hematoma, infection, or asymmetry, and
      aesthetic benefits were achieved even in patients with facial asymmetry.

PMID- 9180705
TI  - Treatment of capillary vascular malformation (port-wine stains) with
      photochemotherapy.
AB  - One-hundred and thirty patients (85 female, 45 male) with port-wine stains were
      treated with photodynamic therapy, also called photochemotherapy, which recently
      has become acknowledged as effective for a variety of malignant tumors. Probably
      based on the photochemical reaction with the generation of toxic species,
      photochemotherapy results in endothelial cell injury and death of abnormal
      capillaries under overlying epidermis. A retrospective review of 118 available
      patients with port-wine stains reveals that 98.3 percent responded to
      photochemotherapy with varying degrees of success after one-time treatment.
      Results were reported under a simple classification system ranging from ordinary
      to dilated to posttreatment type. In the ordinary group, the results evaluated as
      excellent, good, fair, and poor were 37.8, 53.7, 8.5, and 0 percent,
      respectively, before a second treatment; the treated area was an average of 9.8
      (range 7 to 13) cm in diameter. In addition, hypertrophic scars, permanent
      hyperpigmentation, and hypopigmentation were not seen based on proper parameters.
      Photochemotherapy offers a potentially efficient and promising choice based on a
      completely different mechanism from that of selected photothermal therapy with
      the pulsed-dye laser.

PMID- 9180707
TI  - Long-term assessment of early alveolar bone grafts using three-dimensional
      computer-assisted tomography: a pilot study.
AB  - Fifteen patients with complete unilateral cleft lip and palate who had primary
      alveolar bone grafting were studied with computer-assisted tomography at a mean
      age of 12 years. Keeping the maxillary alveolar crest parallel to the plane of
      the scan, 1.5-mm cuts of the maxilla were made from the infraorbital rim to the
      gingival third of the crowns of the teeth. A single operator reformatted the data
      into three-dimensional images using the Maxiview 3200 computer workstation. This
      allowed examination of the position, size, and spatial relationship of the
      grafted area and quantification of the amount of bone coverage of root surface
      and bone height of the alveolus in or adjacent to the graft site. Ten patients
      showed a lateral incisor in the line of the cleft. The average bony coverage of
      these tooth roots was 76.5 percent. In the five patients in whom there was
      lateral incisor agenesis, the canine root had average bony coverage of 82.6
      percent. The average height of bone at the lateral incisor was 8.7 mm; at the
      canine, 14.1 mm. In two patients in whom there was only 42 percent tooth root
      coverage, the teeth were still viable, stable, and without mobility. Computed
      tomographic (CT) scans of the 15 patients demonstrated good graft survival with
      adequate volume. The functional and aesthetic status of the dentition in the area
      of the cleft also was demonstrated.

PMID- 9180708
TI  - Modification of two-flap method and framework construction for reconstruction of
      atypical congenital auricular deformities.
AB  - A single-stage two-flap method utilizing an anteriorly based subcutaneous
      pedicled skin flap and a mastoid fascial flap has been applied successfully for
      reconstruction of lobule-type microtia. This paper presents three modifications
      of the two-flap method, with which atypical congenital auricular deformities
      necessitating both framework construction and coverage were reconstructed
      successfully. In middle and upper auricular deformities such as a concha-type or
      a scapha-type microtia, a cranially based postauricular skin flap and lower
      mastoid fascial flap were used. For upper auricular deformities such as microtia
      representing lop-ear deformity, a narrow cranially based postauricular skin flap
      (Grotting flap) and upper mastoid fascial flap were used. For lower auricular
      deformities such as total absence of the earlobe, a cranially based skin flap and
      lower mastoid fascial flap were utilized. In each deformity the framework was
      totally or partially constructed with autogenous costal, conchal, or septal
      cartilage or their combination according to the size or shape of the defect.
      Fifty-two atypical auricular deformities were corrected with the modified two
      flap method and framework construction. The follow-up has ranged from 4 months to
      3 years (average 18 months). No major surgical complications occurred in this
      series. Representative cases reconstructed with each modified method are shown.
      While the shape of the cartilage framework is sculptured according to the type
      and degree of deformity in each patient, the modified two-flap method not only
      adequately covers the cartilage but also preserves the fabricated framework in
      its natural contour and position in the diverse varieties of atypical congenital
      auricular deformities.

PMID- 9180709
TI  - Ear replantation without microsurgery.
AB  - Reconstitution of the amputated ear remains a challenge to the plastic surgeon.
      Reattachment as a composite graft of the total or subtotal amputated ear is
      unreliable. Microsurgical replantation can be performed in a minority of cases;
      however, difficulty with adequate venous drainage complicates the technical
      complexity of these cases. To enhance survival of a reattached ear segment,
      Mladick et al. advocated use of the retroauricular pocket principle. This
      technique involves deepithelialization of the amputated part, followed by
      anatomic reattachment to the amputation stump and then burial in a retroauricular
      pocket. This simple technique increases the surface area of the avulsed segment
      in contact with surrounding nutrients, maximizing the probability of "take." The
      relationship between the dermis and cartilage is preserved, thus minimizing the
      deformity from cartilage warping. The undisturbed dermis on the involved segment
      can reepithelialize spontaneously, negating the need for a skin graft. We have
      used this technique successfully in five of six patients.

PMID- 9180710
TI  - The axial nasodorsum flap.
AB  - A new axial flap is described for reconstruction of soft-tissue defects of the
      nose, including the supratip and columella. The blood supply to this flap
      originates from the lateral nasal branch of the angular artery adjacent to the
      nasolabial fold. This flap was used in seven patients between 1989 and 1994, and
      there was complete survival. We recognized that this axial nasodorsum flap
      provided suitable shape design in each patient and produced excellent cosmetic
      results. The anatomy, the technique, and our clinical experience are presented.

PMID- 9180711
TI  - The fasciocutaneous supraclavicular artery island flap for releasing postburn
      mentosternal contractures.
AB  - Mentosternal contractures represent a surgical challenge to the plastic and
      reconstructive surgeon. We add the supraclavicular artery island flap to the
      armamentarium of surgical procedures to improve the function and cosmesis of
      disfigured patients. Since July of 1994, the supraclavicular artery island flap
      has been used at our institution for releasing postburn mentosternal contractures
      in eight patients. The flap was planned to be 4 to 10 cm in width and 20 to 30 cm
      in length with the supraclavicular vessels running axially. All donor defects
      could be closed primarily without significant postoperative complications in
      seven of the eight patients. All flaps healed primarily, achieving a good
      functional result by complete removal of contracting scar tissue for all
      patients; one donor site healed by secondary intention. We found the
      supraclavicular artery island flap both reliable and safe for immediate
      resurfacing after resection of cervical scars. The anatomy, operative procedure,
      and postoperative results of the supraclavicular artery island flap are outlined
      in this paper.

PMID- 9180712
TI  - A full-thickness chondrocutaneous flap from the auricular concha for repair of
      tracheal defects.
AB  - A free full-thickness chondrocutaneous flap from the auricular concha for the
      repair of large tracheal defects was transferred successfully. The flap is based
      on the superficial temporal vessels (reversed flow) and the posterior auricular
      vessels. The advantages of this flap for the repair of tracheal defects are (1)
      its dissection is easy, (2) thin components of the flap provide a wide
      postoperative airway, (3) the structure of the reconstructed trachea is made firm
      by the conchal cartilage with vascularization, (4) the highly vascularized
      cartilage results in less resorption than a free cartilage graft, (5) the donor
      site can be repaired easily and is concealed by the remnant auricle, and (6) a
      long arterial pedicle (reversed flow) can be obtained. The disadvantages are (1)
      there may be temporary postoperative congestion of the flap, (2) postoperative
      narrowing of the auriculocephalic sulcus may occur, and (3) a short venous
      pedicle often requires a vein graft.

PMID- 9180713
TI  - Quantitative analysis of facial motion components: anatomic and nonanatomic
      motion in normal persons and in patients with complete facial paralysis.
AB  - The maximal static response assay of facial motion, described in 1994, enables
      the simultaneous measurement of multiple facial motions by tracking the positions
      of specific facial points. While the maximal static response assay provides
      accurate measurement of facial motion, the analysis of these data lacks the
      simplicity of a single-number scale such as the House-Brackmann system, a
      subjective scale traditionally used to classify facial function. The purpose of
      this study was to develop a simplified numerical index capable of summarizing the
      data generated by the maximal static response assay in a clinically meaningful
      way. We also wanted to develop a method whereby only anatomic motion or
      nonanatomic motion in the paralyzed face could be quantitated. Anatomic motion is
      the motion of the specific facial points studied by the maximal static response
      assay that can be attributed solely to the pull of the regional facial muscles
      that govern the movement of those points. Nonanatomic motion is motion that is
      secondary to the pull of the unaffected contralateral muscles that is transmitted
      to the paralyzed hemiface. Thirty-four patients with complete facial paralysis
      were studied. The maximal static response assay was performed on all patients on
      presentation to the Facial Nerve Center at the University of Pittsburgh Medical
      Center or after development of complete facial palsy postoperatively. The data
      from these patients were compared with maximal static response assay data from 26
      unaffected controls. The anatomic index of facial motion and the nonanatomic
      index of facial motion were calculated for all study participants. The anatomic
      index of facial motion measures anatomic facial motion, and the nonanatomic index
      of facial motion measures nonanatomic facial motion. To calculate the anatomic
      index of facial motion, the vector magnitudes of the supraorbital, infraorbital,
      and modiolar motions during brow lift, eye closure, and smile are summed. The
      anatomic index of facial motion represents a ratio of this sum on the affected
      side to the corresponding sum on the unaffected side using only anatomic motions.
      The nonanatomic index of facial motion is a similar ratio using nonanatomic
      motion only (i.e., motions in directions that cannot be produced by the
      ipsilateral muscles). The anatomic index of facial motion represents a single
      number that can be used to assess facial motion. The value of the anatomic index
      of facial motion for patients with complete facial paralysis is 0.07 +/- 0.08.
      The anatomic index of facial motion for normal individuals is 1.05 +/- 0.13 (p <
      0.0001, Mann-Whitney rank-sum test). The nonanatomic index of facial motion in
      normal individuals is 0.05 +/- 0.08; in patients with complete facial paralysis,
      it is 0.34 +/- 0.32 (p < 0.0001, Mann-Whitney rank-sum test). During recovery
      from complete facial paralysis, the anatomic index of facial motion and the
      nonanatomic index of facial motion each revert steadily toward normal values. The
      anatomic index of facial motion and the nonanatomic index of facial motion are
      single numbers based on the maximal static response assay, which quantitatively
      describes anatomic motion and nonanatomic motion in patients with complete facial
      paralysis. Although patients with complete facial paralysis have motion on the
      paralyzed hemiface, the motion is primarily nonanatomic. Both indices can be used
      to track recovery from complete facial paralysis.

PMID- 9180714
TI  - Analysis of 100 cases of free-muscle transplantation for facial paralysis.
AB  - Free-muscle transplantation is the treatment of choice for long-standing facial
      paralysis. It enables the reconstructive surgeon to restore facial movement and
      some emotional animation. Despite all technical innovations and 20 years of
      experience with free-muscle transplantation, the aesthetic and functional
      outcomes of the surgery are still unpredictable. The present report reviews 100
      free-muscle transplantations to the face by a single surgeon and analyzes various
      preoperative, intraoperative, and postoperative factors in relation to the
      functional recovery of the muscle transplants. These factors were demographic
      variables such as age, gender, and etiology as well as intraoperative variables
      such as choice of muscles, number of nerve coaptations, and ischemia time of the
      muscle. Additionally, four independent raters not involved in the care of these
      patients rated standardized preoperative and postoperative videos and judged the
      functional and aesthetic outcomes. From 1981 to 1993, 93 patients with facial
      paralysis underwent free-muscle transplantation. A total of 100 muscles were
      transplanted, since 7 patients received two muscle transplants. There were 33
      male and 60 female patients ranging in age from 3 to 57 years, with an average of
      22.2 +/- 14.9 years. The gracilis muscle was used in 63 cases of free-muscle
      transplantation, while the pectoralis minor was used in 34 cases. In 2 patients a
      segment of the rectus abdominis was transferred, and in 1 patient a small segment
      of the latissimus dorsi was transferred. In 89 patients the onset of muscle
      function was reported. The range was from 6 to 48 weeks postoperatively. The
      average was 21.6 +/- 9.14 weeks after muscle transplantation. The correlations
      showed a trend to earlier onset of function and higher aesthetic rating in young
      female patients. The intraoperative ischemia of the free muscle did not correlate
      with the onset of muscle function. Using a five-step scale of judgments, a higher
      postoperative rating was seen in 94 percent of the patients, and 80 percent of
      all patients achieved a moderate or better result.

PMID- 9180715
TI  - Facial neuromuscular retraining for oral synkinesis.
AB  - The purpose of this paper is to describe the outcome of facial neuromuscular
      retraining for brow to oral and ocular to oral synkinesis in individuals with
      facial nerve disorders. Fourteen patients with unilateral facial nerve disorders
      and oral synkinesis who were enrolled in physical therapy for retraining were
      studied. Synkinesis was measured with quantitative video facial position analysis
      prior to the initiation of physical therapy and at regular intervals during
      retraining. Retraining included surface electromyographic biofeedback-assisted
      specific strategies for facial muscle reeducation and a home exercise program of
      specific facial movements. Twelve of 13 patients with brow to oral synkinesis and
      12 of 14 patients with ocular to oral synkinesis reduced their synkinesis with
      retraining. Patients with a 1-year on greater duration of a facial neuromuscular
      disorder (excluding patients with unusually marked changes) demonstrated a
      significant decrease in brow to oral synkinesis and in ocular to oral synkinesis;
      there was a mean percentage decline in abnormal movement of 60.5 percent (SD =
      26.48) and 30.1 percent (SD = 62.57), respectively. We conclude that brow to oral
      and ocular to oral synkineses associated with partial recovery from facial
      paralysis were reduced with facial neuromuscular retraining for individuals with
      facial nerve disorders.

PMID- 9180716
TI  - Capsular contracture with textured versus smooth saline-filled implants for
      breast augmentation: a prospective clinical study.
AB  - Texturization of silicone-filled breast implants has been shown to reduce the
      incidence of capsular contracture. A double-blind clinical study was undertaken
      to compare this incidence in saline-filled implants with textured or with smooth
      surfaces. Twenty-one women underwent mammary augmentation with a textured implant
      in one breast and a smooth implant in the other. The implants were placed
      subglandularly. All operations were performed by the same surgeon and all follow
      up examinations by another. Breast hardness was evaluated 6 months
      postoperatively with applanation tonometry, using Baker's grading, and after 12
      months, now also with a questionnaire concerning the patient's evaluation.
      Capsular contracture (Baker 3) had occurred in 33 percent of the breasts at the
      end of the study, and was bilateral in five cases. The incidence of contracture
      and the patients' views on the results did not differ between textured and smooth
      prostheses or between right and left breasts. Five patients requested
      reoperation, two of them because of breast hardness. Texturization of saline
      filled implants thus did not reduce the incidence of capsular contracture.

PMID- 9180717
TI  - Reversed saphenous neurocutaneous island flap: clinical experience.
AB  - The description of blood supply to the skin through the superficial perineural
      vascular network has led to the concept of neurocutaneous flaps. Based on
      preexisting anatomic studies, the clinical use of large reversed-flow
      neurocutaneous saphenous island flaps is described. This flap is based on the
      arterial axis associated with the saphenous nerve and the greater saphenous vein
      in the lower leg. The donor area can be closed by soleus muscle advancement over
      the tibia and skin grafting. Five successful cases are reported with a low
      complication rate.

PMID- 9180718
TI  - Morphometric examination of the free scapular flap.
AB  - In this study we investigated the clinicoanatomic basis of the scapular flap by
      morphometric examinations of 42 cadavers. Our findings were as follows: With
      common-trunk type scapular vessels, the maximal lengths of arteries and veins
      that could be used for a flap pedicle were 93 and 91 mm. With direct-type
      scapular vessels, the maximal lengths were 95 and 71 mm. In common-trunk type
      vessels, the mean internal diameter 2 mm distal from the confluence of the
      scapular vessel was 2.8 mm for arteries and 3.3 mm for veins. In the direct-type
      vessels, the mean internal diameter 2 mm distal from the confluence of the
      circumflex scapular vessel was 1.8 mm for arteries and 3.3 mm for veins. The
      maximal superoinferior dimension of the scapular graft was 28 mm. The maximal
      lateral dimension of the scapular graft was 12 mm.

PMID- 9180719
TI  - The infragluteal skin flap: a new option for reconstruction in the perineogenital
      area.
AB  - Use of a local flap is often needed for closure of a defect in the perineogenital
      area. For this we have applied a pedicled skin flap raised in the infragluteal
      fold, the technical details and surgical results of which are presented in this
      paper. From 1985 until 1995, this infragluteal flap has been used to widen the
      vaginal introitus in 6 patients, to reconstruct the labia majora in 5, to close a
      rectovaginal fistula in 4, and to reconstruct the perineal body in 1. In all 16
      patients the flap survived without signs of impaired circulation. The donor scar
      is inconspicuously located in the natural infragluteal plica, not violating any
      anatomic unit. The infragluteal skin flap adds to the surgical armamentarium for
      perineal and genital repair.

PMID- 9180720
TI  - Two-dimensional cephalometric analysis of the effects of subperiosteal palatal
      soft-tissue expansion in growing cats.
AB  - The feasibility and possible effects of palatal soft-tissue expansion in palatal
      repair were studied. A prospective longitudinal animal experiment was performed
      in 75 growing cats assigned to 5 groups. In 31 cats, a midline defect was made,
      and bipediced flaps were raised at the age of 8 weeks (stimulated Langenbeck
      operation) in order to create palatal scars. At the age of 14 weeks, custom-made
      tissue expanders were inserted palatally in 61 animals. Tissue expansion was
      performed by weekly inflation in 33 cats (16 without and 17 with scars) for an 8
      week period. The remaining 28 cats (14 without and 14 with scars) served as sham
      groups. A control group was formed by 14 animals (without scars and without
      tissue expanders). Soft-tissue gain and its effects on maxillofacial growth and
      development were measured in the midsagittal plane on tracings from standardized
      lateral radiographs. The effects of the experimental interventions were evaluated
      for 8 weeks after removal of the tissue expanders. Not all the cats yielded
      results at all time periods. This study showed that soft-tissue expansion of
      palatal mucoperiosteum is feasible. The surgically induced scars did not cause
      significant differences between the different groups in the midsagittal plane,
      and the data from both expansion and sham groups could be pooled. Significant
      soft-tissue gain was achieved by the tissue-expansion technique. Iatrogenic side
      effects were significant anteroposterior growth retardation at the level of the
      bony palate and an increase in vertical growth of the anterior nasomaxillary
      height and the posterior skull height during active tissue expansion. After
      removal of the tissue expanders, some accelerated growth was found in the tissue
      expansion in the scarred tissue group, with initial correction of the abnormal
      growth at the cranial base level. It is concluded that palatal soft-tissue
      expansion is possible in growing cats. This technique, however, impaired
      maxillofacial growth and development.

PMID- 9180721
TI  - Migration of hydroxyapatite onlays into the mandible and nasal bone and local
      bone turnover in growing rabbits.
AB  - To determine the effects of local bone turnover on the migration of macroporous
      hydroxyapatite onlays in the nasal bone and mandibular ramus, we performed
      histomorphometric analyses of the underlying bone area in 41 New Zealand White
      rabbits from the age of 4 weeks. The hydroxyapatite implants were placed under
      the periosteum of the right nasal bone (a depository bone onto its periosteal
      surface and endosteal resorptive) and the mandibular ramus (resorptive onto its
      outer surface). The corresponding left sides were sham operated. Following
      fluorescence bone labeling, composite specimens of the hydroxyapatite block
      including both sides of the nasal bone and mandible were removed at 0 (n = 1), 3,
      6, 9, 12, and 16 weeks postoperatively (n = 8, respectively) and processed to
      yield undecalcified sections. Bone-bone marrow interfaces in the entire area
      within 200 microns beneath the base of the hydroxyapatite and in the counter-area
      on the sham-operated side were measured under a light microscope. In all grafted
      specimens, the hydroxyapatite matrix was directly united with the underlying
      tissue by bone ingrowth. However, the sinking of the hydroxyapatite graft in the
      nasal bone was significant at 3 weeks postoperatively and gradually increased
      thereafter. In the mandible, the sinking became significant at 6 weeks. In the
      nasal bone, the bone area density beneath the graft showed a time-dependent
      decrease during the experimental period, but in the mandibular bone, the value
      was initially decreased at 3 weeks and then recovered to baseline level. In both
      bones, parameters of bone resorption, such as osteoclast number and osteoclast
      surface, were significantly increased from 3 weeks. While the parameters of bone
      formation, such as osteoblast surface and mineralizing surface, were
      significantly decreased from 3 weeks in the nasal bone, they were significantly
      increased in the mandible. Mineral apposition rate showed a significant decrease
      in both bones. Our data indicate that while the bone area density beneath the
      hydroxyapatite seemed to depend on bone formation, increased bone resorption
      would be more critical for the remodeling of underlying bony architecture in the
      migration of the hydroxyapatite graft.

PMID- 9180722
TI  - Bone induction using demineralized bone in the rabbit femur: a long-term study.
AB  - While traditional bone grafting is the standard for replacement of segmental bony
      defects, alternative options (avoiding morbidity of autologous grafts) are
      attractive and continue to be sought. This study attempted to determine whether
      demineralized bone powder could be used reliably to replace a significant bony
      deficit at a weight-bearing site. The long-term functional characteristics of
      this induced bone were analyzed to determine whether it maintained its strength
      and shape and reacted normally to physiologic stress over an extended period of
      time (12 months). In 55 New Zealand White rabbits, a 1-cm length of femur was
      removed (approximately 20 percent of the total length of the rabbit femur). The
      femur was then reconstructed with a titanium mandibular plate, leaving the gap
      intact. In 38 of the animals, this gap was filled with demineralized bone powder
      in an attempt to induce bone to form across the defect. In group 1 (n = 23), the
      mandibular plate remained in place for the duration of the study (12 months). In
      group 2 (n = 15), the plate was removed 8 weeks after placement of the
      demineralized bone powder, and the animals were followed for an additional 12
      months. In group 3 (n = 10), nothing was placed within the bony gap. In group 4
      (n = 7), the gap was repaired with autologous bone graft. All the animals that
      received demineralized bone powder completely filled the osteotomy gap with new
      bone within 6 to 8 weeks after implantation. None of control group 3 formed bone
      across the gap (p < 0.001). Eighty-six percent of control group 4 (autologous
      bone graft) successfully formed bone across the osteotomy gap. In addition, 90
      percent of control group 3 had hardware failure within 8 weeks after surgery
      compared with 0 percent (0 of 38) of the group that received demineralized bone
      powder (p < 0.001). In group 1, analysis after 12 months revealed that the bone
      formed ultimately became thin and easily fractured, most likely because of
      shielding from stress loading by the mandibular plate. In contrast, in group 2
      (in which the plate was removed after 8 weeks), the bone remodeled and
      hypertrophied in response to the physiologic stress of weight bearing and at the
      end of the 12-month period was essentially identical to normal femur. In certain
      circumstances, reconstruction of bony defects using bone-induction techniques may
      be as good as autologous bone grafting, with the advantage of limiting the donor
      site morbidity for the patient.

PMID- 9180723
TI  - The role of platelet-activating factor in musculocutaneous flap reperfusion
      injury.
AB  - Platelet-activating factor is an extremely potent lipid-inflammatory mediator
      implicated in the pathophysiologic mechanism of reperfusion injury in a variety
      of organs. The purpose of this study, employing a porcine latissimus dorsi flap
      model, was to (1) examine the expression of platelet-activating factor and (2)
      evaluate the possible benefit and mechanism of action of platelet-activating
      factor antagonism in musculocutaneous flap reperfusion injury. Experiment 1: In 6
      pigs, bilateral flaps underwent 8 hours of arterial ischemia followed by 12 hours
      of reperfusion. Biopsies were collected sequentially and analyzed
      immunohistochemically for platelet-activating factor expression. Different
      processing techniques, however, were unable to detect specific tissue expression
      of platelet-activating factor. Experiment 2: In 11 pigs, bilateral flaps
      underwent 8 hours of arterial ischemia followed by 20 hours of reperfusion. A
      lipophilic platelet-activating factor receptor antagonist (L-659,989) was
      administered as a single dose to treated flaps by a local intraarterial route
      prior to reperfusion. This treatment augmented the survival of both muscle (48.3
      versus 19.7 percent) and skin (49.8 versus 42.0 percent) components of the flaps
      in a statistically significant fashion (p = 0.001). Experiment 3: In 3 pigs, a
      radiolabeled structural analogue of L-659,989 (14C-L-680,573) was administered to
      flaps in a fashion similar to experiment 2. After 8 hours of ischemia, sequential
      full-thickness flap biopsies were collected over the initial 6 hours of
      reperfusion. The radio-labeled platelet-activating factor receptor antagonist was
      found to be highly concentrated within treated flaps, with gradual decay over the
      initial 6 hours of reperfusion. Experiment 4: Thirty minutes prior to completion
      of 8 hours of arterial ischemia, autologous neutrophils labeled with indium-111
      were reintroduced into the systemic-circulation of 5 pigs. Prior to reperfusion,
      treated flaps received L-659,989 as in experiment 2. Over the initial 4 hours of
      reperfusion, the flaps were imaged in situ by a gamma camera at 3-minute
      intervals. The platelet-activating factor receptor antagonist was found to
      significantly attenuate the accumulation of radioactivity within treated flaps.
      CONCLUSION: Platelet-activating factor expression within musculocutaneous flaps
      subjected to ischemia and reperfusion was non directly demonstrated in this
      study. Still, we have shown that (1) the specific platelet-activating factor
      receptor antagonist L-659,989 is beneficial to the survival of both muscle and
      skin flap components, (2) a single, prereperfusion local dose of this lipophilic
      drug remains concentrated within the flap during the early inflammatory phase of
      reperfusion, and (3) during reperfusion, platelet-activating factor antagonism is
      able to directly or indirectly diminish the accumulation of acute inflammatory
      cells in musculocutaneous flaps.

PMID- 9180724
TI  - Ischemia-reperfusion injury in skeletal muscle: CD 18-dependent neutrophil
      endothelial adhesion and arteriolar vasoconstriction.
AB  - The purpose of this study was to evaluate if the venular neutrophil-endothelial
      adhesion associated with ischemia-reperfusion of skeletal muscle is dependent on
      leukocyte adhesion glycoprotein CD18 function and to determine if this
      interaction influences the vasoactive response in nearby arterioles. An in vivo
      microscopy preparation of transilluminated gracilis muscle in 13 male Wistar rats
      was used for this experiment. Observations of nonischemic muscle (sham)
      demonstrated this preparation to be stable for 8 hours with negligible change in
      neutrophil adherence or arteriole diameter. Three groups were evaluated in this
      study: (1) sham, no ischemia, no treatment (n = 5, 20 arterioles. 20 venules),
      (2) 4 hours of global ischemia only (n = 4, 19 venules, 22 arterioles), and (3) 4
      hours of ischemia plus monoclonal antibody against CD18 (n = 4, 12 venules, 9
      arterioles). The murine monoclonal antibody (WT.3, Seikagaku America, Inc.),
      which binds the rat leukocyte function antigen I CD18 chain, was infused into the
      contralateral femoral vein 30 minutes prior to reperfusion. The number of
      leukocytes rolling and adherent to endothelium (15 seconds of observation) was
      counted in 100-microns venular segments, and arteriole diameters were measured at
      various times during reperfusion. All counts and measurements were normalized to
      baseline preischemic readings for each animal. Mean changes from baseline were
      compared between groups. The increase in ischemia-reperfusion-induced neutrophil
      endothelial adherence in venules was blocked by monoclonal antibody, but rolling
      behavior was not changed. The ischemia-reperfusion-induced progressive
      vasoconstriction in arterioles was blocked by monoclonal antibody. These results
      suggest that (1) neutrophil-endothelial adherence function associated with
      ischemia-reperfusion in this model is CD18-dependent, (2) neutrophil rolling
      function does not appear to be dependent on CD18, and (3) neutrophil CD18
      function is a prerequisite for ischemia-reperfusion-induced arteriolar
      vasoconstriction. These findings provide important mechanistic information that
      may help explain the deleterious microcirculatory events associated with ischemia
      reperfusion injury skeletal muscle.

PMID- 9180725
TI  - E- and L-selectin adhesion molecules in musculocutaneous flap reperfusion injury.
AB  - Definition of the elements governing leukocyte adhesion to the microvascular
      endothelium may lead to new forms of treatment for reperfusion injury. The
      objectives of this study, employing a porcine latissimus dorsi flap reperfusion
      model, were (1) to characterize the expression of E- and L-selectin adhesion
      molecules and (2) to test for a possible benefit of E- and L-selectin blockade in
      the preceding experimental setting. In experiment 1, full-thickness biopsies were
      collected sequentially over an 8-hour ischemia and subsequent 6-hour reperfusion
      period. Immunocytochemistry was performed with monoclonal antibody EL-246, an
      antibody that crossreacts with both E- and L-selectin. In experiment 2, the
      binding of EL-246 to L-selectin on circulating porcine neutrophils was determined
      by flow cytometric analysis. In experiment 3, in situ hybridization was performed
      using complementary RNA probes for detection of endothelial E-selectin mRNA. In
      experiment 4, bilateral flaps were elevated in six pigs and subjected to 8 hours
      of arterial ischemia followed by 20 hours of reperfusion. Flaps on each animal
      were randomly assigned to receive either treatment with a continuous local
      intraarterial infusion of EL-246 (1 mg per flap) or solvent vehicle. Muscle and
      skin survivals were assessed by nitroblue tetrazolium and intravenous fluorescein
      staining techniques, respectively. Computer digitization permitted quantitation
      of relative tissue survival. In experiment 1, specific immunostaining of
      microvascular endothelium was achieved using EL-246. Greater-intensity staining
      was detected in reperfusion than in baseline or ischemic sections. In experiment
      2, flow cytometric analysis indicated specific recognition by EL-246 of isolated
      peripheral porcine neutrophils (> 45 percent staining) as compared with an
      isotype-matched control antibody (< 3 percent staining). In experiment 3, in situ
      hybridization studies demonstrated an early ischemic up-regulation and later
      reperfusion downregulation of E-selectin mRNA during the reperfusion period. In
      experiment 4, administration of monoclonal antibody EL-246 afforded a significant
      augmentation in mean percentage survival of muscle (37.6 versus 18.7 percent, p =
      0.015) and skin (48.6 versus 29.3 percent, p = 0.046). In conclusion, it was
      determined that E-selectin is expressed along the microvascular surface and is
      upregulated and subsequently downregulated during ischemia-reperfusion
      conditions. The monoclonal antibody EL-246 appears to recognize porcine L
      selectin as well as E-selectin. Blockade of E/L-selectin-mediated leukocyte
      adhesion significantly reduces musculocutaneous flap reperfusion injury.

PMID- 9180726
TI  - The influence of arterial inflow and venous outflow on the survival of reversed
      flow island flaps: an experimental study.
AB  - Reversed-flow flaps are currently used for reconstruction of the distal portion
      of the upper and lower extremities. However, detailed experimental studies on the
      reversed-flow flap are lacking, and there have been many clinical reports
      concerning its postoperative complications. In the present study, the effects of
      blood inflow and outflow on flap viability were investigated. Six groups of
      island flaps, which differed in whether arterial inflow and venous outflow were
      retrograde or antegrade, were prepared on the rat's abdomen. The venous pressure
      of the vascular pedicle (n = 5), the blood flow (n = 10), and the survival rates
      of flaps (n = 10) were measured in each group. When arterial inflow was
      retrograde, the viable flap area diminished in proportion to the decrease in
      blood flow. The correlation coefficient between blood flow and survival rates of
      the flaps was 0.885, which indicates that blood inflow to the flap is closely
      related to the area of flap viability. The relationship between the venous
      outflow and the viable flap area was "all or nothing". When venous outflow was
      retrograde, there was either no effect on flap area at all or complete congestive
      necrosis.

PMID- 9180727
TI  - The role of the venous system in the abdominal flap of the rat.
AB  - The abdominal flap of the rat has become a popular model with investigators.
      Recently, researchers have been reporting survival of skin flaps with varying
      blood supplies. We studied the viability of skin flaps on a consistent model with
      varied blood supply. An 8 x 9 cm flap was raised in 40 male Sprague-Dawley rats.
      The viability of the flaps could be studied in 25 rats. The survival of a
      pedicled flap based on the left inferior epigastric artery and vein was compared
      with that of a pedicled flap with enhanced venous drainage. The survival of a
      venous flap based on the paired inferior epigastric veins and the paired long
      thoracic veins was compared with that of an arterialized venous flap. A composite
      graft was used as a control for all groups. A qualitatively improved survival was
      found in the pedicled venous-enhanced group (66 percent) compared with the
      pedicled flaps (56 percent) (p > 0.05). An improved survival was found in the
      arterialized venous flap (57 percent) compared with the venous flap (40 percent)
      (p < 0.05). All flaps had improved survival compared with the composite graft
      (0.6 percent) (p < 0.05).

PMID- 9180728
TI  - Financial disclosure is not full disclosure.

PMID- 9180729
TI  - Histologic effects of the high-energy pulsed CO2 laser on photoaged facial skin.
AB  - To delineate the histologic effects of laser resurfacing at photoaged skin, a
      protocol was designed to biopsy laser test sites in conjunction with adjacent
      actinically damaged skin at the time of rhytidectomy. Five patients with
      photodamaged skin underwent resurfacing of the preauricular region to examine the
      effect of increasing pulse energy and increasing number of passes on depth of
      dermal penetration. Histologic examination of these specimens showed that the
      depth of laser injury was dose-dependent. Increasing pulse energy created a
      deeper wound, and increasing the number of passes similarly produced a larger
      band of necrosis. Ten patients with photodamaged skin underwent resurfacing of
      the preauricular region 15 days to 6 months prior to undergoing a rhytidectomy. A
      comparison of the laser-resurfaced test spot with the adjacent untreated
      photodamaged skin demonstrated consistent histologic changes to both epidermis
      and dermis in all specimens examined. Following laser resurfacing, epidermal
      atrophy and atypia were eliminated, and all specimens exhibited a regeneration of
      epithelium that was normal in its morphology. Melanocytic hypertrophy and
      hyperplasia were corrected following treatment, although density and function of
      epidermal melanocytes appeared normal. All specimens exhibited a substantial
      amount of neocollagen formation involving both the superficial and middermis
      following resurfacing. In association with new collagen development within the
      dermis, there was noted to be a similar degree of proliferation of elastic
      fibers, as well as a diminution of glycosaminoglycans, which are typically
      present in actinically damaged elastotic dermis. To determine the effect of laser
      resurfacing on-black skin, laser test spots were placed in the postauricular
      region of three black patients. Biopsy of these test sites showed that the
      histologic effects of laser resurfacing were similar to those observed in
      Caucasian patients, with complete repopulation of epidermal melanocytes in
      specimens biopsied 3 months following resurfacing. The histologic effects of
      laser resurfacing are microscopically similar to those of phenol peeling in terms
      of the amelioration of photodamage. The distinction between these two treatment
      methods lies in their apparent effect on epidermal melanocytes, which appear to
      function normally following laser resurfacing.

PMID- 9180730
TI  - If it's dead, does it make any difference how it got there?

PMID- 9180731
TI  - Aggressive surgical treatment of digital papillary adenocarcinoma.
AB  - The case of a 38-year-old white man with digital papillary adenocarcinoma is
      presented. It is a lesion of the skin often occurring in the digits of the hand
      or of the feet. This disease is rare and has not been reported in the plastic
      surgical or orthopedic literature to date. A case report is presented here along
      with our rationale for aggressive surgical treatment consisting of amputation.

PMID- 9180732
TI  - Treatment for congenital synostosis of the fourth and fifth metacarpals with the
      hemicallotasis technique.
AB  - The hemicallotasis technique was used to treat the fifth metacarpal in a hand
      with congenital synostosis of the fourth and fifth metacarpals. Lengthening and
      correction of the metacarpal were achieved simultaneously. Continuous traction
      eliminated further soft-tissue procedures. The appearance and function of the
      hand were much improved.

PMID- 9180733
TI  - Reversed free osteoarthrocutaneous dorsalis pedis flap for simultaneous
      reconstruction of the trapeziometacarpal joint and the first metacarpal bone.
AB  - Simultaneous reconstruction of a traumatic defect of the trapeziometacarpal joint
      and the first metacarpal with a composite dorsalis pedis flap is described. The
      transplant, consisting of the second metatarsal and the second
      metatarsophalangeal joint, was reversed at the defect site for the
      metatarsophalangeal joint to become a new trapeziometacarpal joint. A long
      vascular pedicle was necessary for direct micro-vascular anastomoses to the
      radial vessels at the wrist. This transfer can be expected to be effective in
      reconstructing composite hand defects involving the trapeziometacarpal joint and
      the entire first metacarpal bone.

PMID- 9180734
TI  - The repair of multiple rectovaginal fistulas with the neurovascular pudendal
      thigh flap (Singapore flap).

PMID- 9180735
TI  - A new approach for the treatment of recurrent large abdominal hernias: the
      overlap flap.
AB  - In this article we report a new technique for the treatment of recurrent large
      abdominal hernias and skin laxity: the overlap flap. This technique combines
      abdominoplasty with hernia repair. Obese patients with recurrent large abdominal
      hernias and skin laxity could benefit from this operation. This operation could
      not be performed in patients with a wide absence of the abdominal wall. A total
      of six patients were treated with this technique in our clinic. Follow-up of the
      patients has ranged from 1 to 4 years. Cosmetic results were excellent in all
      patients. No recurrence of the hernias has been observed in any of the patients.
      Two flaps are prepared; the lower one is deepithelialized, and it is used as an
      autogenous mesh in place of a prosthetic material to reinforce the abdominal
      wall, and the upper flap is prepared and overlapped on this lower one.

PMID- 9180736
TI  - Repair of incomplete simple syndactyly by a web flap on a subcutaneous tissue
      pedicle.
AB  - A new web flap on a subcutaneous tissue pedicle was developed to repair
      incomplete simple syndactyly. It was isolated from the top skin in syndactyly and
      transferred down into the depth of the web space to create a web commissure. With
      use of this technique, aesthetic appearance of the web and well-functioning
      fingers were gained. Moreover, this technique made full use of the original skin
      of the syndactyly, and a skin graft was not needed. We report here the operative
      technique, which presents another alternative for repair of incomplete simple
      syndactyly.

PMID- 9180737
TI  - Use of a tourniquet in panniculus resection.
AB  - The tourniquet technique is simple and provides an efficacious method for
      panniculectomy. Time spent during surgery and anesthesia can be offered.
      Furthermore, less fat necrosis can be anticipated because of the reduced use of
      electrocautery, which in turn should decrease the risk of seroma formation and
      infection.

PMID- 9180738
TI  - Wrap-around cartilage flap for correction of unilateral cleft lip nose deformity.
AB  - A turnover contralateral cephalic alar cartilage flap is suggested for the
      correction of cleft nose alar deformity. The cartilage flap from the normal side
      wraps around the deficient medial crus and acting as a pulley reposition and
      augments the affected alar cartilage. The satisfactory and long-lasting results
      obtained in our small series seem to justify this approach for improving cleft
      nasal deformities, and we think it should be available in our surgical
      armamentarium.

PMID- 9180740
TI  - Congenital upper eyelid retraction treated with gold weight implantation.

PMID- 9180739
TI  - UltraPulse carbon dioxide laser with CPG scanner for deepithelialization:
      clinical and histologic study.
AB  - The UltraPulse carbon dioxide laser with CPG scanner was utilized to
      deepithelialize dermal pedicles in breast reduction inferior pedicle flaps.
      Clinical advantages include lack of bleeding, markedly shortened time of
      dissection, and excellent wound healing. Histologic studies confirm that the
      laser removes epidermis and papillary dermis but leaves undamaged the superficial
      vascular plexus and reticular dermis.

PMID- 9180741
TI  - Fixation of alloplastic facial implants with lag screws.

PMID- 9180742
TI  - Light at the beginning of the carpal tunnel?

PMID- 9180743
TI  - A simple method to prepare a custom-made finger splint using a disposable
      hypodermic syringe.

PMID- 9180744
TI  - Laparoscopic cholecystectomy through prolene mesh after bilateral TRAM flap.

PMID- 9180745
TI  - The salvage of a degloved hand skin flap by arteriovenous shunting.

PMID- 9180746
TI  - Microsurgical replantation of the avulsed scalp.

PMID- 9180747
TI  - Triglyceride-filled breast implants.

PMID- 9180748
TI  - Bleed of and biologic response to triglyceride filler used in radiolucent breast
      implants.

PMID- 9180749
TI  - Exploration of intracranial structures endoscopically.

PMID- 9180750
TI  - A review on the history of end-to-side neurorrhaphy.

PMID- 9180751
TI  - The TRAM flap for breast reconstruction.

PMID- 9180752
TI  - Breast reduction under intravenous sedation: a review of 50 cases.

PMID- 9180753
TI  - Preservation of the inframammary fold: a plea for close follow-up.

PMID- 9180754
TI  - Cosmetic versus reconstructive surgery.

PMID- 9180755
TI  - The expanded forehead scalping flap: a new method of total nasal reconstruction.

PMID- 9180756
TI  - An easy method for scalp injury dressing with the patient's own hair.

PMID- 9180757
TI  - Mechanical analysis of explanted silicone breast implants.

PMID- 9180758
TI  - The fate of teeth transfixed by osteosynthesis screws.

PMID- 9180759
TI  - Pedicle modification in the Lejour vertical scar reduction mammaplasty.

PMID- 9180760
TI  - Computer indexing of journal references.

PMID- 9180761
TI  - Subcutaneous living sparganum worms.

PMID- 9180762
TI  - A mental health information centre--integrating technology and community.

PMID- 9180763
TI  - How to do research on a shoestring.

PMID- 9180764
TI  - Outcome of first-episode schizophrenia and the new antipsychotics. A literature
      review.

PMID- 9180765
TI  - Criteria for fitness to stand criminal trial.
AB  - OBJECTIVE: To identify criteria whereby triability can be determined. DESIGN:
      Questionnaire survey. The final rating was decided on the basis of a structured
      psychiatric interview. SETTING: Oranje Hospital, Bloemfonteln. PARTICIPANTS: A
      total of 736 questionnaires was sent to 176 judges of the Supreme Court, 480
      magistrates and 32 attorneys-general and state advocates in South Africa and
      Namibia, and 33 psychiatrists and 15 clinical psychologists working in forensic
      psychiatric units in South Africa. With the information from the completed
      questionnaires, rating criteria were compiled. The rating criteria were applied
      by means of a structured interview to 100 persons referred in terms of section
      77(1) of the Criminal Procedure Act 51 of 1977. A multiprofessional psychiatric
      team was requested to evaluate the same 100 observandi independently. RESULTS: A
      total of 298 (40.5%) of the questionnaires were returned. From the data of the
      completed questionnaires, 19 legal items, 17 psychiatric items, 2 special
      laboratory tests and 2 psychosocial items were identified as the most important
      and clear diagnostic indications for the evaluation of triability. The similarity
      between the findings of the researchers and those of the multiprofessional
      psychiatric team was meaningful to 1% of significance. For the proper application
      of the criteria a cut-off point of 31 was determined. A score of 31 or higher
      therefore indicates that a patient is unfit to stand trial, while a score of less
      than 31 indicates triability. CONCLUSIONS: The application of the proposed final
      rating criteria as a single method of rating is at the very least just as
      reliable as the multiprofessional team in evaluating fitness to stand trial. The
      proposed criteria, used as a single rating instrument, are cost-effective in
      terms of time and staff, avoid unnecessary hospitalisation and ensure that
      mentally ill accused will have a fair trial.

PMID- 9180766
TI  - Informant questionnaires as screening measures to detect dementia. A pilot study
      in the South African context.
AB  - OBJECTIVES: There is currently no appropriate cognitive screening test available
      to diagnose dementia cross-culturally in South Africa. The aim of this pilot
      study was to investigate the efficacy of an informant questionnaire in detecting
      cognitive decline in the elderly. DESIGN: The Deterioration Cognitive Observee
      (DECO), an informant questionnaire previously used abroad, was administered to
      relatives of elderly patients. Relatives were also asked a series of open-ended
      questions about the patient's cognitive abilities and behaviour. The DECO results
      were compared with patients' scores on the Mini-Mental State Examination (MMSE),
      the cognitive measure currently used to assess a patient's level of cognitive
      decline, as well as with the clinicians' diagnosis. SETTING: The interviews were
      completed at the Groote Schuur Hospital Geriatric Clinic during the months of May
      and June 1994. SUBJECTS: The subjects were patients (N = 20) and their relatives
      (N = 20) attending the Geriatric Clinic. RESULTS: DECO scores correctly predicted
      normal functioning in 7 patients and dementia. In 8. The DECO scores correlated
      with the MMSE scores (r = 0.625; P < 0.01) and MMSE scores correlated with the
      clinicians' diagnosis (chi 2 = 0.114; df = 1; P = 0.73). Open-ended questions
      confirmed the clinicians' diagnosis. CONCLUSION: The DECO was found to predict
      dementia correctly in all but the severely demented patients. As the DECO appears
      to be a suitable alternative to cognitive testing, it should be considered as a
      possible screening measure for dementia in elderly people in South Africa.

PMID- 9180767
TI  - Lyme disease in South Africa.
AB  - OBJECTIVE: This article presents an overview of Lyme disease (LD) as it applies
      to neuropsychiatry and summarises research results on the epidemiology of LD in
      South Africa. METHOD: The study is based on a review of research papers from
      various medical disciplines that focused on the epidemiology of LD in South
      Africa. RESULTS: Assessment of the incidence of LD in South Africa is based on a
      few anecdotal studies. The results of the studies are dominated by experimental
      weeknesses. CONCLUSIONS: The sporadic nature of LD Incidence in South Africa may
      either reflect a restriction of research efforts or be a true indication of the
      epidemiology of the disease. This review lends support to the former hypothesis.
      The low reported incidence of LD in South Africa is probably due to a lack of
      awareness and research effort.

PMID- 9180768
TI  - Adolescent psychiatry--inpatient diagnostic trends.

PMID- 9180769
TI  - Treatment of childhood obsessive-compulsive disorder with citalopram.

PMID- 9180770
TI  - Obsessive-compulsive disorder with unusual themes.

PMID- 9180771
TI  - Comprehensive management of non-insulin-dependent diabetes mellitus. A diabetes
      clinic revisited.
AB  - OBJECTIVE: To 'revisit' the Johannesburg Hospital diabetes clinic to ascertain
      whether the established risk factors for CAD were being identified and
      appropriately managed. DESIGN: Body mass indices (BMI), fasting lipograms and
      glycated haemoglobin (HBA) estimations were done on a random sample of white
      NIDDM patients aged over 35 years. RESULTS: Eighty-two patients (39 males, 43
      females) were tested. The mean age was 60 years (range 36-80 years) and the mean
      duration of NIDDM 6.2 years (range 1-25 years). The mean HBA value was 10%
      (normal 4-8%). Obesity was present in 82%; it was moderate (BMI 25-30 kg/m2) in
      46% and severe (BMI > 30 kg/m2) in 36%. Hypercholesterolaemia was present in 46%,
      hypertriglyceridaemia in 68%, and both in 34%. Uncontrolled hypertension was
      present in 20% of patients, and 27% smoked. CONCLUSIONS: Management of patients
      at our clinic remains confined to the control of hyperglycaemia. Despite
      increased awareness of the risk factors for CAD, these factors have largely been
      ignored.

PMID- 9180772
TI  - Public sector primary care of diabetics--a record review of quality of care in
      Cape Town.
AB  - AIM: To evaluate the quality of health care received by diabetics. DESIGN:
      External audit by means of retrospective record review. SITE: Ambulatory
      outpatient diabetes clinics at community health centres in black areas of Cape
      Town. METHOD: A stratified random sample (520) of all patients who attended any
      of five health centres during 1991 was reviewed by a clinician who had been
      trained to do structured record reviews. RESULTS: The response rate was 73.1%. Of
      all patients reviewed 91% had non-insulin-dependent diabetes mellitus and the
      remainder insulin-dependent diabetes mellitus; 65% were female and 35.8% were
      employed. Only 35% attended optimally. Fingerprick blood glucose values were
      recorded at 98.4% of visits, blood pressure was recorded at 74.1% of all visits
      and for 97.4% of patients; urine dipstick test results were recorded at 84.6% of
      visits and for over 99% of patients in 1991, and weight was recorded at 68.8% of
      visits. In contrast, fundoscopy was recorded for 6% of patients and examination
      of the feet was performed in 4.7% of patients. Fewer than half (48.9%) of visits
      resulted in any change in management. Polypharmacy is frequent, with an average
      of 2.3 non-hypoglycaemic drugs prescribed per visit. CONCLUSION: Attendance and
      examination for treatable complications are inadequate. Care is routinised and
      reactive and there is polypharmacy. RECOMMENDATIONS: Simple but appropriate
      protocols and matching in-service education are likely to improve the care of and
      health outcome for diabetics at these sites.

PMID- 9180773
TI  - Driving and diabetics on insulin therapy.
AB  - Patients with diabetes mellitus who require insulin therapy have always been
      thought to be at high risk of motor vehicle accidents, primarily because of the
      possibility of hypoglycaemic events while driving. There are, however, no
      specific guidelines in South Africa that allow for a rational decision as to when
      a diabetic is medically fit to drive. The Road Traffic Ordinance simply states
      that 'Patients with uncontrolled diabetes should be forbidden to drive'. No
      guidelines are given as to what constitutes 'uncontrolled diabetes'. The
      situation is not much clearer internationally, where various countries have
      different laws in this regard. Diabetics on insulin therapy are not restricted
      from driving private vehicles in any country, but the laws regarding commercial
      vehicle driving by diabetics on insulin are widely disparate. The actual
      increased risk of motor vehicle accidents incurred by diabetic drivers on insulin
      is also uncertain, there being wide variations in the risk rate in different
      publications. Literature review does suggest, however, that diabetics are
      probably at a slightly increased risk of traffic violations and accidents
      compared with the general population, but that this increased overall risk is
      slight and probably acceptable. There are, however, no known actual statistics
      for South Africa and any rational guidelines on driving for diabetics on insulin
      in this country will need to be based on international experience, mostly gleaned
      from the USA and Western Europe. The decision as to whether a diabetic on insulin
      should be allowed to drive (either a private vehicle or, more often, a commercial
      vehicle) is frequently left to the attending doctor. Appropriate guidelines,
      based on international experience, are suggested.

PMID- 9180774
TI  - Diagnosis of Cushing's syndrome.
AB  - No single test has a 100% diagnostic accuracy, and combinations of tests are
      required. We routinely obtain 3 baseline IRMA-ACTH levels, followed by CRF
      stimulation and overnight high-dose (8 mg) dexamethasone suppression (HDS). If
      ACTH-independent adrenal disease is suspected, thin-section CT (with or without
      isotope scanning) of the adrenals is performed. In ACTH-dependent Cushing's
      syndrome, the clinical manifestations in conjunction with the CRF and 8 mg
      overnight HDS tests are used to differentiate pituitary from ectopic ACTH
      production. If plasma ACTH increases > 34% following CRF, and plasma cortisol
      decreases > 60% after HDS, pituitary MRI is the next step; if not, the ectopic
      ACTH syndrome is more likely and IPSS and attempts to localise the source of the
      ACTH production are required (see algorithmn).

PMID- 9180775
TI  - Prevention of corticosteroid-induced osteoporosis.

PMID- 9180776
TI  - Breastfeeding recommended for HIV+ women.

PMID- 9180777
TI  - Opinions on the abortion legislature.

PMID- 9180778
TI  - Improving care for patients undergoing curettage for incomplete abortion.

PMID- 9180779
TI  - Induction of labour at term--misoprostol, efficacy, economics and ethics.

PMID- 9180780
TI  - An economic appraisal of a mobile cervical cytology screening service.
AB  - OBJECTIVE: Cervical cytology screening is widely accepted as an important
      strategy in the control of cervical cancer. With increasing competition for
      health resources the need for information on the cost-effectiveness of different
      screening programmes has become critical. This paper describes the cost of
      screening via a mobile clinic, and compares the cost-effectiveness of screening
      via a mobile clinic with that of screening at established clinics. METHOD: Data
      were obtained from work studies, review of clinic and health authority records
      and key informant interviews. In addition to describing the actual cost of the
      project over the first year, a projection is made of the cost of operating the
      mobile clinic under non-research conditions. Sensitivity analysis is used to
      adjust for differences in yield and follow-up in comparing the cost-effectiveness
      in each setting. RESULTS: The cost of the project over 1 year was R185,795. The
      projected cost of running such a project under non-research conditions for 1 year
      is R291,858. The cost-effectiveness of screening at the mobile clinic was 57%
      less than that of screening at the established clinics. Sensitivity analysis
      indicated that for any given yield and follow-up rate, the projected cost
      effectiveness of screening at the mobile clinic is 15-28% less than for the
      established clinics. CONCLUSION: These findings raise questions about the
      appropriateness of using mobile clinics in areas where there are established
      health services.

PMID- 9180781
TI  - Cervical cytology screening--knowledge, attitudes and practice in a peri-urban
      settlement.
AB  - AIM: To determine the knowledge, attitudes and practice of women living in peri
      urban settlements with regard to screening for cervical cancer. METHOD: A
      community-based questionnaire survey of 165 women living in a defined area of
      Khayelitsha, a peri-urban settlement on the outskirts of Cape Town. RESULTS: Two
      hundred households were visited, with a response rate of 84%. Median age of
      respondents was 27.5 years. The majority of interviewees were married (53.3%),
      unemployed (61.5%), had an educational status of standard 4 or less (58.1%) and
      had been living in Cape Town for 4 years or more (64.3%). The median parity was 2
      (range 0-11). Most interviewees were currently using contraception (52.4%). One
      third (35.4%; 95% CI 28.1-42.7%) of interviewees had heard of the Pap smear. Of
      these women, most had obtained their information from the midwife obstetric unit
      (MOU), and this was the most commonly reported facility where Pap tests were
      known to be done. The majority of interviewees did not regard the test (or the
      prospect thereof) as embarrassing (88.4%), painful (89.1%) or harmful (90.9%),
      and indicated that they would have the test done (89.1%). The most important
      reason for choice of where the test should be done was proximity to place of
      residence (83.9%). More than one-third of interviewees reported having had a Pap
      test (37.2%; 95% CI 28.8-44.8%). The most common reason for not having had a test
      was that the interviewee had never heard of it (81.3%). Most had undergone the
      test at a MOU (65.6%), where it had been part of an antenatal work-up (80.3%).
      Fewer than half of the interviewees who had undergone a test knew the result of
      their test. CONCLUSION: The antenatal, obstetric and family planning services in
      the area have been effective, to a limited extent, in providing information and
      conducting screening. However, these services are missing many opportunities to
      fulfill this function, and knowledge and practice of cervical cytology screening
      in this community are poor. With the implementation of a rational policy for
      screening in this area there is the potential to achieve good coverage.

PMID- 9180782
TI  - Laparoscopically assisted vaginal hysterectomy (LAVH)--an alternative to total
      abdominal hysterectomy.
AB  - OBJECTIVE: To assess the feasibility of performing laparoscopically assisted
      vaginal hysterectomy (LAVH) on women referred for total abdominal hysterectomy
      (TAH). DESIGN: Prospective intervention study on women referred for TAH from a
      gynaecological outpatient clinic. SETTING: Groote Schuur Hospital, Cape Town.
      This institution accepts patient referrals from community hospitals and family
      physicians for hospitalised care. PATIENTS: Forty-one consecutive women referred
      for TAH were suitable for LAVH. Women able to undergo conventional vaginal
      hysterectomy, women with uterine fibroids exceeding 14 weeks in size and subjects
      with malignant disease were excluded. The most common indication for hysterectomy
      was persistent abnormal bleeding. INTERVENTION: Of the 41 women assessed pre
      operatively as suitable for LAVH, the procedure was successfully performed in 40
      by means of a bipolar desiccation and scissors transection technique with re
      usable equipment. MAIN OUTCOME MEASURES: Assessment of intra-operative and
      postoperative morbidity, surgical complications, operating time, length of
      hospitalisation and assessment at postoperative visit 6 weeks after surgery.
      RESULTS: Only 1 woman was unable to undergo successful LAVH because she had
      pelvic adhesions and densely adherent loops of bowel; a TAH was performed. No
      operative complication occurred. One woman had postoperative vaginal bleeding
      controlled with a vaginal pack, and a diagnosis of von Willebrand's disease was
      subsequently established. No patient had febrile morbidity and when reviewed at
      clinic 6 weeks later all women were well. CONCLUSIONS: LAVH is possible in many
      women in whom hysterectomy is indicated but conventional vaginal hysterectomy is
      not feasible. In this study LAVH was found to be a safe procedure with minimal
      complications.

PMID- 9180783
TI  - Balloon valvuloplasty for severe mitral valve stenosis in pregnancy. A report of
      11 cases.
AB  - Balloon valvuloplasties for severe mitral stenosis were performed on 11 pregnant
      patients with excellent results and no complications. The mitral valve area was
      increased from a mean of 0.9 cm2 to 2.1 cm2. There was no clinically significant
      mitral regurgitation. The pregnancies proceeded normally to delivery at or near
      term, with no maternal or perinatal morbidity or mortality.

PMID- 9180784
TI  - Is routine caesarean section necessary for breech-breech and breech-transverse
      twin gestations?
AB  - OBJECTIVE: To determine if perinatal outcome is affected by the route of delivery
      in breech-breech and breech-transverse twin gestations. DESIGN: Prospective
      observational study. SETTING: Umtata General Hospital, a referral hospital for
      approximately 32 rural hospitals throughout the former transkei. SUBJECTS: Twin
      gestations with breech-breech and breech-transverse presentations. MAIN OUTCOME
      MEASURES: Birth weights, 5-minute Apgar scores and neonatal mortality rates among
      41 women who underwent vaginal delivery were compared with those of 27 who
      underwent transverse lower-segment caesarean sections. RESULTS: A total of 68
      women were involved in the study. Forty-one were delivered vaginally and 27
      underwent transverse lower-segment caesarean sections. The vaginal delivery group
      consisted of 35 breech-breech and 6 breech-transverse twin gestations, while the
      caesarean section group comprised 25 breech-breech and 2 breech-transverse
      presentations. Both twin I and twin II in the caesarean section group were bigger
      than their respective counterparts delivered vaginally (P < 0.02 for twin I and P
      < 0.01 for twin II). There were no statistically significant differences in
      either 5-minute Apgar scores or neonatal mortality rates between the two groups.
      CONCLUSION: Vaginal delivery of breech-breech and breech-transverse twin
      gestations appears a reasonable option provided criteria for vaginal breech
      delivery are adhered to.

PMID- 9180786
TI  - Is shoe size a reliable obstetric predictor of cephalopelvic disproportion?

PMID- 9180785
TI  - Laparoscopic findings in women with chronic pelvic pain.
AB  - OBJECTIVE: This study was undertaken to assess the spectrum of pelvic pathology
      observed at laparoscopy in women with chronic pelvic pain, and to compare women
      with an identifiable cause of pain to those with no visible pelvic pathology,
      with regard to symptomatology and demography. DESIGN: Retrospective case control
      study reviewing laparoscopy reports and patient records. SETTING: Department of
      Obstetrics and Gynaecology, Groote Schuur Hospital. PATIENTS: One hundred and
      thirty-six consecutive women undergoing laparoscopic assessment for undiagnosed
      pelvic pain of at least 6 months' duration, between 1989 and 1991. MAIN OUTCOME
      MEASURES: The presence of endometriosis, pelvic adhesions, other pelvic pathology
      and 'negative' laparoscopic findings was assessed. The association between pelvic
      pathology and specific symptomatology, fertility, contraceptive use, past pelvic
      surgery, ethnic group and smoking is examined. RESULTS: No cause of pain was
      identified at laparoscopy in 30% of these patients, while endometriosis was found
      in 16% of women and pelvic adhesions in 40%. The 41 women with no identifiable
      laparoscopic abnormality did not differ significantly from the 95 with pelvic
      abnormalities in respect of age, parity, duration of pain, frequency of
      dysmenorrhoea and dyspareunia or the presence of gastro-intestinal or urinary
      symptoms. However, injectable hormonal contraception use was more common in the
      group with negative laparoscopic findings and smoking was more common among the
      women with pelvic pathology. CONCLUSION: Chronic pelvic pain with a
      laparoscopically normal pelvis is a common problem in Cape Town, occurring with a
      frequency similar to that reported from various overseas centres. Women with this
      problem are not readily identified by demographic profile or symptom complex.

PMID- 9180787
TI  - 'Never say die'--survival of a woman with massive abruptio placentae and a
      haemoglobin concentration of 0.6 g/dl.

PMID- 9180789
TI  - A novel obstetric speculum.

PMID- 9180788
TI  - Appropriateness of referrals for the hypertensive disorders of pregnancy from the
      MOUs in Cape Town.

PMID- 9180790
TI  - Management of inflammatory bowel disease--an alternative approach?

PMID- 9180791
TI  - Absorption of high-dose enteral vitamin A in low-birth-weight neonates.
AB  - A randomised, double-blind placebo-controlled trial was designed to determine
      whether high-dose (25,000 IU) enteral vitamin A, to correct deficiency, would be
      absorbed and well tolerated in low-birth-weight (LBW) neonates. Thirty-five LBW
      infants (950-1700 g; gestational age 27-36 weeks) were allocated to receive
      either placebo or vitamin A (25,000 IU) via nasogastric tube on the first day of
      the study (between 36 and 60 hours after delivery). The dose was repeated on
      study days 4 and 8. Serum retinol concentrations were determined pre- and post
      supplementation. Toxic effects of vitamin A were monitored by noting vomiting,
      drowsiness and irritability, and palpating for a bulging fontanelle. The mean
      serum retinol concentration was significantly higher following supplementation in
      the vitamin A-treated group than in the placebo group (45.77 +/- 17.07
      micrograms/dl v. 12.88 +/- 6.48 micrograms/dl; P = 0.0001). Toxic effects were
      not detected in any of the infants. In conclusion, high-dose enteral vitamin A is
      well absorbed in LBW neonates and three doses of 25,000 IU given over a period of
      8 days are not associated with any detectable toxic effects.

PMID- 9180793
TI  - Nutrition news from Nkhoma, Malawi, 1995.

PMID- 9180792
TI  - The interplay between nutrition and body composition.

PMID- 9180794
TI  - Tuberculosis in the intensive care unit.

PMID- 9180795
TI  - Factors associated with poor prognosis in very-low-birth-weight infants.
AB  - OBJECTIVE: To evaluate predictors of poor outcome, including the CRIB (Clinical
      Risk Index for Babies) score, in a local population of very-low-birth-weight
      (VLBW) infants, in order to provide guidelines for selection of these babies for
      expensive tertiary care. SUBJECTS: Two hundred and thirty-one neonates born at
      less than 31 weeks' gestation and/or weighing between 1001 g and 1500 g, enrolled
      prospectively as part of a multicentre study evaluating the CRIB score. DESIGN:
      Univariate analysis (chi-square/t-tests) and multivariate analysis (stepwise
      logistic regression) on the above sample to determine predictors of poor outcome.
      SETTING: Neonatal Unit, Johannesburg Hospital. OUTCOME MEASURES: Death or
      impairment (namely oxygen therapy > 28 days, grade 3 or 4 intraventricular
      haemorrhage, or ventricular enlargement). RESULTS: Poor outcome was predicted by
      birth weight, lowest oxygen requirement in the first 12 hours (which are two
      components of the CRIB score), and maximum partial arterial carbon dioxide
      pressure (PaCO2) in the first 72 hours. Other factors, including the full CRIB
      score, were not predictive of outcome. CONCLUSIONS: One method of selection of
      infants for expensive tertiary care is on the basis of predicted outcome. Birth
      weight remains a reasonable basis for this selection, but the inclusion of other
      factors, such as oxygen requirement, would improve accuracy. The CRIB score was
      not a suitable means to select infants in the local context, but may be of value
      in international comparisons.

PMID- 9180796
TI  - Introduction of a donor exposure reduction programme for multiple-transfused very
      low-birth-weight infants.
AB  - OBJECTIVE: To conduct an audit of the frequency of red cell concentrate
      transfusions (RCCTs) in infants of different weight categories, the donor
      exposure rate (DER), in these transfused infants and the volume of blood wasted
      during each transfusion, and to identify from this baseline information specific
      categories of infants who would benefit from the introduction of a limited donor
      exposure programme (LDEP). STUDY SETTING: Neonatal wards and neonatal intensive
      care unit (NICU), Tygerberg Hospital, Western Cape. STUDY DESIGN: A prospective
      descriptive study and comparison with a historic control group. SUBJECTS:
      Information on the birth weight, age at the time of each RCCT and number of blood
      donors to whom an infant was exposed were collected post factum for all infants
      admitted to the neonatal wards and NICU between May 1993 and May 1994. During
      this time, the red blood cell concentrate was supplied as single paediatric bags
      (180 ml) transfused within 14 days of donation. An LDEP was introduced in
      February 1995. With this system, red blood cells were supplied as triple packs: a
      main unit of 250 ml with three empty satellite packs allowing up to three
      separate transfusions. These were assigned to a specific infant and were to be
      transfused within 21 days of donation. A second system where one adult blood bag
      was divided into two 180 ml bags and assigned to one infant to be transfused
      within 35 days of donation was also assessed. RESULTS: Of the 7854 infants
      admitted during the first 12-month audit period, 387 (4.9%) received 977 RCCTs.
      Of these, 183 (47.3%) received one transfusion, 72 (18.6%) two transfusions, 51
      (13.2%) three transfusions, 27 (7.0%) four transfusions and 54 (13.9%) five or
      more transfusions. Infants (N = 188) with a birth weight below 1500 g admitted to
      the NICU were identified as the group with the highest prevalence of RCCTs
      (68.6%), and it was therefore decided that in the prospective study such infants
      would qualify for the LDEP. A total of 81 infants was transfused with either the
      double (N = 47) or the triple bags (N = 34) over a 5-month period. The decrease
      in the mean DER (+/-SD) was clinically significant when the triple (1.9 +/- 0.8)
      (P = 0.0001) and the double bags (1.6 +/- 0.8) (P = 0.0001) were compared with
      the previous single-bag system (4.4 +/- 3.5). Of concern was the large mean
      volume of concentrated red cells (118.5 +/- 12.5 ml) wasted per transfusion with
      the single-bag system. CONCLUSIONS: This survey confirmed a high RCCT rate as
      well as a very high DER in very-low-birth-weight (VLBW) infants treated at a
      tertiary centre. By assigning a triple or double bag of red cells from one blood
      donor and extending the storage of blood for small-volume RCCTs in infants from
      14 days to 35 days, donor exposure was reduced significantly. We urge the
      introduction of the multibag blood transfusion system and extended storage period
      of blood for small-volume RCCT for VLBW infants in South Africa.

PMID- 9180798
TI  - A new paradigm--assessment of functioning and the WHO's ICIDH.

PMID- 9180797
TI  - Paradoxical symmetry of the chest in neonates--a new clinical sign in the
      diagnosis of a unilateral pneumothorax.

PMID- 9180799
TI  - Communication and psychiatry in Africa.

PMID- 9180800
TI  - Quality of life and pharmaco-economic aspects of obsessive-compulsive disorder. A
      South African survey.
AB  - OBJECTIVE: The quality of life and pharmaco-economic aspects of obsessive
      compulsive disorder (OCD) have received relatively little research attention to
      date. We aimed to gather preliminary data on these in a South African patient
      sample. DESIGN: A survey of members of the Obsessive-Compulsive Disorder
      Association of South Africa was undertaken by means of a detailed self-report
      questionnaire. RESULTS: Results of the survey suggest that OCD causes significant
      morbidity, leading to clear distress and Interference with academic,
      occupational, social and family function. Unfortunately, correct diagnosis and
      appropriate treatment have been delayed in many patients, and the financial costs
      of such incorrect management are likely to be considerable. CONCLUSION: Much
      further work needs to be done by the medical profession and by interested
      consumers to raise awareness about OCD and to provide information about its
      management. In South Africa, it is particularly Important to undertake such
      psycho-education at a primary health care level and to impact on patients of low
      socio-economic status.

PMID- 9180801
TI  - Pica and the obsessive-compulsive spectrum disorders.
AB  - BACKGROUND: The concept of a spectrum of obsessive-compulsive related disorders
      may have clinical and research heuristic value in the approach to disorders
      similar to obsessive-compulsive disorder (OCD) in respect of phenomenology and
      psychobiology. Like other repetitive and ritualistic behaviours, pica may be
      postulated to fall at times on this spectrum. METHODS: Five cases of pica seen at
      our clinics are presented here in order to test this hypothesis. Phenomenology,
      neurobiology (where available) and pharmacotherapy data are provided in order to
      consider a possible relationship with OCD and OCD spectrum disorders. RESULTS: In
      2 of the cases, pica appeared to be a compulsion and patients had additional
      symptoms which met diagnostic criteria for OCD. In 2 of the cases, the clinical
      picture and neurobiological data were reminiscent of an impulse control disorder.
      Four of the 5 patients responded to treatment with a serotonin re-uptake
      inhibitor (SRI). CONCLUSION: These results are consistent with a hypothesis that
      at least some cases of pica may usefully be conceptualised as lying within a
      compulsive-impulsive spectrum of symptoms and disorders.

PMID- 9180803
TI  - Guidelines to the management of disability claims on psychiatric grounds.

PMID- 9180802
TI  - Obsessive-compulsive disorder in black South Africans--a case series.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) has been shown to be highly
      prevalent in both developing and developed countries. Nevertheless, data on OCD
      in blacks, and black South Africans in particular, are limited. METHOD: Records
      of patients presenting with OCD at a tertiary hospital serving a predominantly
      black population were reviewed. Patient data, including demographic Information,
      presenting symptoms and clinical course, were collated. RESULTS: Six black South
      Africans had presented with OCD in the previous year. Phenomenology and
      psychopharmacology of the disorder were largely reminiscent of those previously
      reported in the International literature. CONCLUSION: Not surprisingly, black
      South Africans may suffer from OCD. Nevertheless, it is likely that such patients
      do not present for treatment or are underdiagnosed. Future rigorous
      epidemiological research on OCD in South Africa is necessary.

PMID- 9180804
TI  - Cats and obsessive-compulsive disorder.

PMID- 9180805
TI  - A case of pica--neither a compulsion nor an impulse.

PMID- 9180806
TI  - Sleep paralysis presenting with reactive depression.

PMID- 9180807
TI  - Eating breakfast--does it make a difference?

PMID- 9180808
TI  - Cognitive and behavioural effects of a school breakfast.
AB  - The cognitive and behavioural effects of a school breakfast were explored in a
      study of 55 children in Grade II and Standard 1 at a farm school outside
      Johannesburg. A previous study had confirmed widespread undernutrition and
      micronutrient deficiencies among the children. For comparative purposes, 55
      children at an inner-city school, among whom no signs of undernutrition were
      found, were assessed in the same way. Three different types of measures of
      attention, distractibility, short-term memory and activity level were used:
      psychometric testing of the children; teacher ratings of children's classroom
      behaviour, and coded video-recorded classroom behaviour. A pre- and post-test
      design was employed to assess the effects of a school breakfast, continually in
      place in the experimental school for a period of 6 weeks. The results indicated
      significant change from pre- to post-test assessment among the experimental
      children in respect of the psychometric measures, teacher-rated hyperactivity and
      video-recorded classroom behaviour. With regard to the latter measure, the
      children showed a decline in both the occurrence and duration of off-task and out
      of-seat behaviour, and an increase in active participation in class and positive
      peer interaction. While the children in the comparison group also showed some
      changes from pre- to post-test, probably attributable to the effects of
      observation, familiarity with the test materials and developmental change, the
      changes were not generalised or consistent. The findings support the conclusion
      that a school breakfast programme had a beneficial effect on the cognitive and
      behavioural performance of socially disadvantaged, undernourished children in
      their first 2 years of school.

PMID- 9180809
TI  - A rapid method of monitoring the acute phase response in a rat model.
AB  - The acute phase response (APR) is accompanied by major changes in micronutrient
      status. It is important to be able to quantitate the degree of APR, which can
      then be related to the accompanying alterations in micronutrient levels. A rapid
      and convenient means of achieving this, viz. the use of an animal model in which
      APR can be induced, would facilitate such an investigation. The aim of the
      present study was to establish, by means of a rat model, a rapid procedure to
      identify APR which is less time-consuming and less expensive than the more
      traditional enzyme-linked immunosorbent assay and radio-immunoassay. Blood was
      drawn immediately prior to, and at 24, 48, 72 and 96-hour intervals post
      inducement of the acute phase. The serum was deproteinised and treated with a
      dye, Auramine O, which specifically binds the acute phase protein alpha 1-acid
      glycoprotein (AAG), the latter remaining in solution after deproteinisation. The
      product formed is a fluorescent addition compound. With fluorescence
      spectrophotometry, levels of AAG were determined and the extent of APR monitored.
      A progressive and reproducible increase in AAG was observed, the highest
      fluorescence intensity recorded after 48 hours; this indicated a mean value (N =
      5) of 9.4 mg/ml from zero at baseline. With a spiking approach, a mean AAG
      recovery of 96% was obtained. The validated methodology, less expensive and less
      time-consuming than existing procedures, which rapidly detects AAG in rat serum,
      provides a simple technique for monitoring the APR process in these animals.

PMID- 9180810
TI  - Anti-oxidants and coronary heart disease.

PMID- 9180811
TI  - Anti-oxidant supplementation in disease prevention--panacea or poison?

PMID- 9180812
TI  - 'Gestational' diabetes mellitus--in the eye of the beholder?

PMID- 9180813
TI  - Gestational diabetes. A window in the development of non-insulin-dependent
      diabetes mellitus.

PMID- 9180814
TI  - The use (and abuse) of reference centiles with an application to weight gain in
      pregnancy.
AB  - Centile charts are commonly used in many areas of health research and practice,
      e.g. growth charts for children, Doppler ultrasonography in pregnancy and
      assessment of cholesterol levels at different ages. Yet there are a number of
      aspects of both their construction and application that are problematic and it is
      some of these issues that will be raised in this paper. The objective of the
      paper is to outline, in a non-technical way, some of the issues that need to be
      considered by the practitioner in estimating and using reference centile charts,
      but which frequently are either not known or ignored. These include: (i) the
      choice of reference population; (ii) how to estimate centiles; (iii) formally
      incorporating previous measurements on an individual, e.g. the interpretation of
      a child's weight that is on the 50th percentile for its age will be different if
      it has been moving along the 90th percentile at previous ages than if it has
      consistently been on the 50th percentile; and (iv) evaluation of centile charts
      used as a screen for problems. The concepts are introduced using an aspect of a
      study conducted at Tygerberg Hospital where centile charts for maternal weight
      gain in pregnancy were developed and assessed for their usefulness in detecting
      light-for-gestational-age (LiGA) births. The reference centile charts for
      maternal weight show poor discriminating ability between LiGA and normal births.
      These results support arguments in favour of abandoning the routine weighing of
      pregnant women.

PMID- 9180815
TI  - Are high uric acid levels in patients with early pre-eclampsia an indication for
      delivery?
AB  - OBJECTIVE: To compare the perinatal mortality rates of pre-eclamptic patients
      with high, normal and low uric acid levels. DESIGN: Prospective analytic study.
      SETTING: Tertiary hospital to which many patients with severe pre-eclampsia are
      referred. SUBJECTS: Two hundred and twenty-nine patients with severe pre
      eclampsia. INTERVENTION: Delivery for maternal or fetal reasons, not taking uric
      acid levels into account. MAIN OUTCOME MEASURE: Perinatal mortality rate.
      RESULTS: The mean uric acid level prior to delivery at a mean gestational age of
      30.9 weeks was 0.4 mmol (SD 0.11). Twenty patients had uric acid levels of 0.28
      mmol/l or lower and 25 patients values of 0.52 mmol/l or higher. The mean
      gestational age at admission and the admission-delivery interval for the high,
      normal and low uric acid groups were 29.2 weeks, 11.8 days; 29.2 weeks, 13.3 days
      and 27.1 weeks, 13 days respectively. For babies who weighed 1000 g or more at
      delivery, the perinatal mortality rates were 40, 11 and 50 respectively.
      CONCLUSION: There is no evidence from this study to support the association
      between perinatal deaths and higher uric acid levels in patients with severe pre
      eclampsia.

PMID- 9180816
TI  - The impact of the manual vacuum aspiration (MVA) technique on health care
      services at Queen Elizabeth Central Teaching Hospital, Blantyre, Malawi.
AB  - OBJECTIVES: To assess the impact of the manual vacuum aspiration (MVA) technique
      on health care services and its acceptability to patients and staff. DESIGN:
      Prospective descriptive survey. SETTING: The university teaching hospital,
      Blantyre, Malawi. PARTICIPANTS: All 456 patients who had MVA for treatment or
      investigation between 10 January and 9 April 1994, the nurses and doctors working
      in the unit and hospital administrators. MAIN OUTCOMES: Proportion of incomplete
      abortion patients who had MVA, the need for pain relief, patients' reactions,
      staff opinion, and reduction in ward occupancy rates and duration of
      hospitalisation. RESULTS: Of the total, 97.4% had MVA for treatment of incomplete
      abortion; these comprised 81.2% of all incomplete abortion patients treated
      during the study period. The mean volume of uterine contents was 33.4 ml. There
      was no relationship between the volume and either the gestational age or uterine
      size (P > 0.05). Only 10.7% of patients required pain relief. The bed occupancy
      rates in the gynaecological ward dropped from an average of 150% before to 130%
      after the introduction of MVA, and the mean hospital stay was reduced from 3
      days, with 78.4% staying for more than 2 days, to 2 days, with 52% staying for
      less than 24 hours (P < 0.05). Most patients expressed general satisfaction with
      the method, while the staff were happler because their work had been made easier.
      There were no major complications associated with the procedure. CONCLUSION: The
      findings show that MVA is a safe, reliable, effective and acceptable method of
      treating incomplete abortion, and can conserve hospital resources.

PMID- 9180817
TI  - The prevalence of domiciliary deliveries in Khayelitsha, Cape Town.
AB  - OBJECTIVE: To determine whether the 17% decrease in the number of patients cared
      for at the Khayelitsha Midwife Obstetric Unit (MOU) between 1991 and 1994 could
      be ascribed to an increase in home deliveries. METHOD: Survey of Khayelitsha
      labour ward records, vaccination cards and family planning statistics at various
      clinics in Khayelitsha, Cape Town. RESULTS: The prevalence of home deliveries in
      Khayelitsha during the study period was estimated at 8%. Between 1992 and 1994,
      the number of acceptors at family planning clinics in Khayelitsha increased by
      89%. CONCLUSION: As the number of home deliveries had apparently remained static,
      it was unlikely that an increase in the former had been responsible for the
      observed decrease in Khayelitsha MOU patients. Other possible reasons for the
      decline, viz. (i) an increase in hospital deliveries; (ii) an increase in the
      number of patients returning to the so-called homelands to be delivered there;
      (iii) an increase in confinements by private doctors and midwives; and (iv) that
      patients had shunned the MOU, were equally unlikely. The decline in the number of
      patients cared for at Khayelitsha MOU between 1991 and 1994 was most likely due
      to the evident success of the local family planning programme.

PMID- 9180818
TI  - Norplant in South Africa--the first 100 patients.
AB  - High maternal mortality rates coupled with poor socioeconomic conditions in
      developing countries indicate the need for those truly dedicated to improvement
      of maternal well-being to investigate advances in methods of pregnancy regulation
      and to implement those found to be effective and acceptable. In a trial involving
      100 patients at Tygerberg Hospital that commenced in December 1993, Norplant was
      found to be highly acceptable and easy to use. It is strongly recommended that
      the acceptability of Norplant to the general South African population be
      evaluated further and then, hopefully, made available to all our people without
      undue delay.

PMID- 9180819
TI  - An economic appraisal of a mobile cervical cytology screening service.

PMID- 9180820
TI  - Cytoscopy as a diagnostic procedure in the investigation of chronic pelvic pain.

PMID- 9180821
TI  - The effect of amniotic fluid suctioning during caesarean section on intestinal
      motility.

PMID- 9180822
TI  - Postgraduate training in psychiatry.

PMID- 9180823
TI  - Marital rape.

PMID- 9180824
TI  - Community psychiatry and rural services--an overview.

PMID- 9180825
TI  - Abnormal eating attitudes in secondary-school girls in South Africa--a
      preliminary study.
AB  - OBJECTIVES: To document the existence of eating attitudes that may reflect
      current, pre- or subclinical eating disorders. To establish preliminary
      prevalence figures for abnormal eating attitudes. DESIGN: Cross-sectional survey
      of eating attitudes. SETTING: Non-clinical, community-based. SUBJECTS: Female
      high-school pupils. OUTCOME MEASURES: Total score derived from a self-report
      questionnaire, Eating Attitudes Test (EAT-26), which measures eating attitudes.
      Factor profile describing dimensions of eating-related psychopathology, derived
      from the clustering of questions on the EAT-26. RESULTS AND CONCLUSIONS: An
      overall prevalence figure of abnormal eating attitudes of 21.66% was documented.
      Black pupils had a higher prevalence than white pupils (37.5% v. 20.67%). The
      factor profile of respondents with abnormal eating attitudes did not differ
      between the race groups, although within the total sample, black respondents had
      a significantly stronger drive toward thinness. A significant developmental
      continuum was established, with prevalence figures for abnormal eating attitudes
      increasing with each standard from Standard 7 onward. The study provides
      preliminary epidemiological data on the prevalence of adolescent girls either
      suffering from or at risk of the development of an eating disorder. In addition,
      the study also provides evidence of the need for intervention strategies that
      commence in the pre-teen years.

PMID- 9180826
TI  - Factors influencing eating attitudes in secondary-school girls in South Africa--a
      preliminary study.
AB  - OBJECTIVES: To establish factors in the environment, e.g. family, peer or media,
      as well as individual factors, e.g. self-perception, which may influence eating
      attitudes. DESIGN: Cross-sectional survey. SETTING: Non-clinical, community
      based. SUBJECTS: Female high-school pupils. OUTCOME MEASURES: Responses to
      questions pertaining to environmental as well as individual factors for each
      respondent ('dieting questionnaire'; self report). Total scores derived from a
      self-report questionnaire pertaining to eating attitudes (Eating Attitudes Test
      (EAT-26)). Statistical analysis, using analysis of variance procedures, to
      determine significant associations between the two questionnaires. RESULTS AND
      CONCLUSIONS: Specific individual wishes, perceptions, behaviours and topics of
      conversation appear to influence as well as predict eating attitudes. Family,
      especially maternal, factors play a role in determining eating attitudes. Peer
      and media (television) factors are not significantly influential. The findings
      provide preliminary data on factors that influence eating attitudes in a group at
      risk for the development of eating disorders. The findings have implications for
      the formulation of preventive strategies within a comprehensive treatment
      approach.

PMID- 9180827
TI  - Buspirone is an effective augmenting agent of serotonin selective re-uptake
      inhibitors in severe treatment-refractory depression.
AB  - BACKGROUND: Buspirone has previously been reported to be effective in the
      augmentation of the antidepressant effect of serotonin selective re-uptake
      inhibitors (SSRIs) in depressed outpatients. We report on buspirone augmentation
      of SSRIs in severe treatment-refractory depression in inpatients. METHODS: A
      retrospective chart review was undertaken of patients diagnosed with DSM-III-R
      major depression and treated at our inpatient unit. All 14 patients had been
      given structured depression rating scales before and after addition of buspirone
      to a SSRI. RESULTS: Patients had previously failed multiple trials of
      antidepressants, often including lithium and/or thyroid augmentation, as well as,
      in 12 cases, electroconvulsive therapy. However, augmentation of an SSRI with
      buspirone led to a rapid and significant improvement in depression in 6 of 14
      (43%) patients. CONCLUSION: Despite the limitations of the study design, our
      results support previous work suggesting the need for further controlled research
      on the use of buspirone in the augmentation of the antidepressant response to the
      SSRIs.

PMID- 9180829
TI  - ICU care for tuberculosis patients--fielding on the boundary.

PMID- 9180828
TI  - The neurobiology and pharmacology of depression. A comparative overview of
      serotonin selective antidepressants.
AB  - BACKGROUND: Over the past decade, targeted drug design has led to significant
      advances in the pharmacological management of depression. A serendipitous
      approach to drug discovery has therefore been replaced by the development of
      drugs acting on predetermined neurobiological targets recognised to be involved
      in the pathology of depressive illness. The first of these 'designer drugs', were
      the selective serotonin (5-HT) re-uptake inhibitors (SSRIs), followed more
      recently by venlafaxine and nefazodone which, in addition to 5-HT uptake, also
      target noradrenaline (NA) uptake and 5-HT2 receptors, respectively. METHODS: This
      paper reviews the biochemistry and pharmacology of depression. From this
      foundation, the relevance of 5-HT selectivity is discussed followed by a
      comparison of the clinical pharmacology and pharmacokinetics of 5-HT-selective
      antidepressants. RESULTS: Despite their common action on synaptic 5-HT uptake,
      structural heterogeneity among the group allows differences to be observed in
      kinetic and pharmacological parameters, viz. plasma half-life (T1/2), liver
      metabolism, protein binding, receptor affinities and selectivity ratios. This not
      only leeds to different attributes which assist in the successful management of a
      particular patient, but will also predict subtle difference in drug interaction
      risks and in side-effect profiles of clinical relevance. CONCLUSION: 5-HT
      selective antidepressants may be more dissimilar than similar, and these
      differences can allow the clinician to identify clinically reliable determinates
      predicting side-effects and, possibly, to identify suitable patients for a
      particular drug.

PMID- 9180830
TI  - Diarrhoea in the intensive care unit.

PMID- 9180831
TI  - Nitric oxide has little effect on acute pulmonary hypertension and right
      ventricular function during acute respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate the effect of nitric oxide (NO) on acute pulmonary
      hypertension and right ventricular function in patients with acute respiratory
      distress syndrome. DESIGN: A prospective clinical study. PATIENTS: Ten patients
      in the respiratory and surgical intensive care units were used. They met the
      criteria for acute respiratory distress syndrome and were significantly hypoxic.
      They were all ventilator-dependent at the time of the study. INTERVENTION: NO was
      delivered to the patients in 5, 10, 20 and 30 ppm doses for 30 minutes at each
      concentration. The dosing was not randomised. MEASUREMENTS AND RESULTS: The
      general and central haemodynamics were measured. Right ventricular function and
      interaction with the pulmonary artery impedance (Ea) were quantified with the
      ratio of right ventricular stroke work index/Ea. NO did not decrease the raised
      pulmonary artery pressure found in all of the patients. Right ventricular
      coupling to the circulation did not improve during the administration of NO.
      CONCLUSION: NO did not relieve the acute pulmonary artery hypertension associated
      with acute respiratory distress syndrome. As a consequence of this, right
      ventricular function failed to improve during the administration of NO.

PMID- 9180832
TI  - Conditional evaluation of broncho-alveolar lavage in mechanically ventilated
      patients with suspected unilateral lobar pneumonia.
AB  - OBJECTIVE: In an attempt to improve our ability to diagnose the cause of
      ventilator-associated pneumonia (VAP), we explore the usefulness of the
      conditional evaluation of bronchoalveolar lavage (BAL) samples from the involved
      and non-involved areas in patients with suspected unilateral lobar VAP (UL-VAP).
      DESIGN: Prospective study. SETTING: University teaching hospital intensive care
      unit. PATIENTS: We studied 19 consecutive patients with suspected UL-VAP.
      MEASUREMENTS AND MAIN RESULTS: Nine of the 12 patients (47%) developed UL-VAP.
      There was a significant difference between the involved and non-involved areas in
      UL-VAP patients (P < 0.001) in respect of the quantitative bacterial cultures
      (QBCs) of BAL samples for each micro-organism, whereas there was no difference in
      patients without UL-VAP. When we applied the criterion of usual BAL (one micro
      organism in concentrations > 10(5) colony-forming units per millilitre) for UL
      VAP diagnosis, the sensitivity was 100%, the specificity 70%, the positive
      predictive value 75%, and the negative predictive value 100%. When we used the
      conditional evaluation of the BAL results for UL-VAP diagnosis, in the involved
      and non-involved areas, the sensitivity was 78%, the specificity 90%, the
      positive predictive value 87.5% and the negative predictive value 82%. A
      statistically significant difference was found when we compared the difference in
      QBCs between the BAL samples for each micro-organism, between the involved and
      non-involved areas in patients with and without VAP (P < 0.001). CONCLUSION:
      These data suggest that utilisation of the conditional evaluation of the QBCs of
      BAL samples improves significantly our ability to diagnose the cause of UL-VAP.

PMID- 9180833
TI  - Severe soft-tissue infections--a diagnostic challenge. The need for early
      recognition and aggressive therapy.
AB  - OBJECTIVES: This article was written to highlight the difficulty in diagnosing
      necrotising fasciitis (NF) and in differentiating it from other severe soft
      tissue infections, and to stress the need for early aggressive therapy in all
      severe soft-tissue infections. METHOD: Four cases of severe soft-tissue infection
      admitted to Baragwanath Hospital Intensive Care Unit between January 1993 and
      March 1996 are reported, presenting the relevant clinical features. RESULTS: The
      clinical diagnosis of NF when used alone was found to be unreliable and the
      diagnosis appeared to be made late in the course of the disease. Late diagnosis
      makes intensive care (largely supportive therapy) of limited value. CONCLUSION:
      Astute clinical awareness and prompt therapy for severe soft-tissue infections
      are needed to enable the early diagnosis of these syndromes and thus prevent
      their serious sequelae. This should include a thorough knowledge of these
      conditions and predisposing risk factors. For comparative purposes specific
      defining clinical criteria are required. Even with full intensive care support,
      severe soft-tissue infections are associated with a significant mortality rate.

PMID- 9180834
TI  - Biotransformation of taxoids by human cytochromes P450: structure-activity
      relationship.
AB  - The metabolism of paclitaxel and docetaxel by human liver microsomes was
      investigated in vitro. The main metabolite of paclitaxel formed in vitro was the
      6 alpha-hydroxypaclitaxel: its formation largely exceeded the formation of other
      metabolites hydroxylated on the lateral chain by rat liver microsomes and
      initially characterized in rat bile. In contrast, in vitro studied showed that
      the initial metabolite of docetaxel resulted from the hydroxylation of the tert
      butyl of the lateral chain at C13 and that the same metabolites were formed in
      human and animal models. Comparison of individual CYP protein content of human
      microsomes and catalytic activities with taxoid biotransformation, showed that 2
      distinct isoforms were assigned to the 6 alpha-hydroxylation (CYP2C) and to the
      hydroxylation of the lateral chain (CYP3A4). Chemical and immunological
      inhibitions confirmed these assumptions. The effect of antineoplastic drugs
      potentially associated with taxoids during chemotherapy has been tested in vitro
      on paclitaxel and docetaxel biotransformations. In the therapeutic range,
      vincristine, vinblastine, doxorubicine and cisplatin elicited a moderate or no
      inhibition of paclitaxel and docetaxel metabolism, as well as cimetidine,
      ranitidine and diphenylhydramine used to prevent major side effects associated
      with taxoid therapy. In patients given barbiturates, the hydroxylation on the
      lateral chain of paclitaxel and docetaxel was markedly stimulated and resulted
      from the induction of CYP3A isoforms. These results clearly demonstrated that the
      biotransformation of paclitaxel and docetaxel by human liver microsomes was
      supported by 2 distinct CYP proteins and that drug interactions could modify the
      therapeutic efficiency of taxoids during chemotherapy.

PMID- 9180835
TI  - [Predictive factors of local recurrence of in situ intraductal carcinoma. Apropos
      of 217 cases].
AB  - The authors have reviewed 217 cases of pure intraductal carcinomas with a mean
      follow-up of 98 months (with 2 deaths out of 31 recurrences from which 35% into
      adenocarcinomas). The data concerning the diagnosis, the tumor size, the
      pathological type, the surgical treatment, more of less associated to radiation
      therapy are detailed. The aim of this work was to give a more reliable way or
      approaching the recurrence rate (31/217) to be able to apply a more conservative
      treatment to these cases. The lymph node dissection and removal seams to be
      useless in the in situ carcinomas. Concerning the tumor size, the local tumors
      can be treated by conservative surgical procedures and do not get any benefit
      from radiotherapy. The opposite is true concerning more largely invasive tumor.
      Concerning the histology, the non-comedocarcinomatous tumors get less benefit
      from radiotherapy than the comedocarcinomatous type. The study of the tumor
      limits and the reliquats seem to be useful. The treatment chosen and applied
      remains the major prognostic element in the probability of recurrence.

PMID- 9180836
TI  - [High dose ifosfamide at 15 g/m2/cycle: a feasibility study in 10 patients].
AB  - Ifosfamide is one of the most efficient antimitotic in soft tissue sarcoma. To
      try to find a possible dose-effect, 10 patients with advanced pretraited relapsed
      soft tissue sarcoma received 15 g/m2/cycle ifosfamide in continuous infusion
      during 5 days. A pharmacokinetic study was done for 2 patients. All patients
      received growth factors, ondansetron and 8 clonazepam. Renal toxicity was
      evaluated after the first and the second cycle. Twenty two cycles were delivered
      to patients who have been already treated with ifosfamid (10 patients with 15
      g/m2 to 54 g/m2, median 27 g/m2) or cis platinum (2 patients). No major renal or
      neurologic toxicity was observed; only subclinical modifications of urinary
      enzymes excretion were found. Two patients had visual hallucinations at the end
      of a cycle and just in the 2 following days; another presented a neuropathy of
      inferior limbs. Hematological toxicity was very limited. Pharmacokinetic study
      did not show induction mechanism at this dosage and with this type of
      administration. So ifosfamide 3 g/m2 during 5 days is feasible. The few level of
      complications observed is perhaps linked to the daily dose of 3 g/m2 instead of 4
      g/m2 or more used in the other studies.

PMID- 9180837
TI  - [Negative second-look laparatomy in ovarian cancers. Survival analysis and
      prognostic factors from 64 cases treated at the Gustave Roussy Institute].
AB  - This study describes 64 cases of ovarian adenocarcinoma seen in the Gustave
      Roussy Institut between 1978 and 1988 and who had a negative second-look
      laparotomy. The median age was 51 years (30-74). FIGO stages were: I: 7 (11%);
      II: 3 (5%); III: 39 (61%); IV: 3 (5%); and undetermined: 12 (19%). There were 53%
      of serous type, 14% of endometrioid type, 13% of undifferencied type, 8% of clear
      cells type, 3% of mucinous type, and 9% of mixed type tumors. There were 50% of
      grade 3 tumors. Initial debulking surgery was as complete as possible in 59
      patients, with a residual tumor after surgery superior or equal to 2 cm in 25
      patients. Post second-look surgery treatment (n = 57) consisted of chemotherapy
      (CT) alone in 22 patients (34%), radiotherapy (RT) alone in 31 patients (49%),
      and CT associated with RT in 4 patients (6%). Median follow-up is 100 months. The
      overall survival rates at 3 and 5 years were respectively 86 and 81%, and disease
      free survival rates 70 and 61%. Among the 64 patients, 26 relapsed (39%). Median
      time to relapse was 96 months. There is a statistical difference in the survival
      between patients who had no or inferior to 2 cm residual tumor and others.
      Residual tumor was the only factor to be significant in univariate and
      multivariate analysis of survival.

PMID- 9180838
TI  - [Evaluation of survival and prognostic factors of 2,000 broncho-pulmonary cancers
      registered during 10 years in a multidisciplinary oncology department].
AB  - Two thousand lung cancer patients were registered as Grenoble's university
      hospital joint oncology clinic from 1/1/1982 to 12/31/1991. These cases consisted
      of 449 small cell lung cancers (SCLC) and 1,551 non-small cell lung cancers
      (NSCLC). SCLC patients had a 4.6% and 2.9% survival rate at 5 and 10 years and
      only 7.2% of patients had a survival longer than 30 months. The main prognostic
      factors for survival were age, sex, TNM stage and WHO performance status. There
      was no increase in survival during the 2 periods of the study. NSCLC patients had
      a 14% and 7% survival rate at 5 and 10 years. Among 727 stage III or IV patients
      not treated with surgery, 2% were alive at 30 months. The main prognostic factors
      for survival were age, histology, TNM stage and WHO performance status. There was
      no increase in survival during the 2 periods of the study.

PMID- 9180839
TI  - [Prevalence assessment of colorectal and breast cancers in the Rhone-Alpes area].
AB  - Prevalence of malignant neoplasm is a basic health indicator used in order to
      evaluate needs in medical equipment for treatment and follow-up of cancer
      patients. Data on prevalence are regularly published by Northern European
      countries. Thames and Connecticut cancer registries. In France available
      information on prevalence are scanty, because follow-up of cancer patients is not
      easy. Therefore, we used a statistical method to evaluate prevalence from
      incidence and mortality in the Rhone-Alpes area (France, 5,300,000 inhabitants)
      in 1990, using the department of Isere population based registry. For females,
      figures for breast carcinoma and colorectal carcinoma are respectively 25,000 and
      5,700, and, for males, 5,700 colorectal carcinoma. For 5 year partial prevalence,
      these figures are respectively 11,300, 3,100 and 3,500. The ratio
      prevalence/incidence is 8.9 for breast in females, 5.8 for colorectal carcinoma
      in females and 4.8 for colorectal carcinoma in males with a steep decrease for 5
      year partial prevalence (4 for breast carcinoma, 3.1 for females colorectal
      carcinoma and 2.9 for males colorectal carcinoma). These ratios are consistent
      with those observed elsewhere in Europe.

PMID- 9180840
TI  - [Prevalence of cancer, health care and daily life assistance in people aged 75 or
      over living in the Tarn area (France)].
AB  - The association between cancer and dependence was estimated using a cross
      sectional study among persons 75 years of age or-older in Tarn county (area with
      a cancer registry recognized by the National Committee of Registries). A
      representative random sample stratified on age, sex, and size of district, was
      drawn using the electoral registers. Each person randomly selected answered the
      questions of a surveyor about previous history of cancer, aid in daily life
      activities and use of health care. Among 5,161, the questionnaire was filled for
      3,368 persons (participation: 65.3%). Only 2.3% declared a past history of cancer
      (cancers diagnosed before 1982 and cancers of the skin excluded). After
      verification 12.6% of the men and 5.2% of the women in the sample were found in
      the registry. This result shows a very high tendency for people not to declare
      their disease. From 75 years of age, 1 man among 8, and 1 woman among 20 suffer
      or have suffered from a cancer during the last 12 years. Only a weak association
      between prevalence of cancer and aid in daily life activities could be found,
      probably explained by the important polymorbidity existing in this age group. The
      persons who suffered from cancer, are not more often confined in bed or in old
      people's home. Regarding use of health care, they see a nurse or their general
      practitioner more frequently, they have been operated or admitted in the hospital
      more frequently than persons without a past history of cancer. Persons with a
      past history of ear-nose-throat cancer differ from other cancers by needing more
      aid to go out of their home, and by taking medical advice more frequently. Except
      for the ear-nose-throat cases, cancer (aside from the acute stage) does not
      generate more dependence or hinder the quality of survival, in comparison to
      those of people of the same age.

PMID- 9180841
TI  - [Male breast cancer in Africa, Apropos of 5 cases at the Ouagadougou University
      Teaching Hospital (Burkina Faso)].
AB  - A retrospective study of male breast cancer was undertaken at Ouagadougou
      University Teaching Hospital over a 3 year period (1993-1996). Authors report 5
      cases representing 4.16% of all breast cancers. The patients' mean age was 61
      years. The average duration of signs and symptoms before the diagnosis was 13
      months. Clinically all the 5 cases presented advanced cancers (4 T4N2M0, 1 T4N2M1
      according to UICC TNM System) with size ranging from 5.5, to 11.5 cm. Histology
      found: 2 medullary infiltrating carcinoma, 1 canalar infiltrating carcinoma, 1
      colloid mucous carcinoma and 1 lobular infiltrating carcinoma. All patients had
      mastectomy associated with axillary clearance in 4 cases. Radiotherapy,
      chemotherapy and hormonotherapy were not associated because unavailable in
      Burkina Faso. Three patients died: the first, 10 days after surgical treatment
      and the 2 others respectively after 14 and 17 months. We have lost sight 1
      patients. The last one is still alive. Authors find that to get better prognosis,
      it is important to improve medical and technical means, to increase information
      and to promote early detection.

PMID- 9180842
TI  - Relaxin and breast cancer.
AB  - Relaxin is a peptide hormone of luteal origin with a broad range of biological
      activities on tissues and organs of the female reproductive system as well as on
      other targets not directly related to the reproductive function. The mammary
      gland is one of the major targets for relaxin, which has been shown to promote
      growth and differentiation of mammary parenchyma and stroma. Based on the
      recognition of the mammotrophic action of relaxin, further research could show
      that this peptide also influences the behaviour of breast cancer cells in vitro.
      In fact, when relaxin was added to the culture medium of MCF-7 breast
      adenocarcinoma cells for short exposure times it had a biphasic effect on their
      growth, stimulating cell proliferation at low, nanomolar concentrations and
      inhibiting it at high, micromolar concentrations. In the longer times, relaxin
      had a marked growth-inhibitory effect on MCF-7 cells at any concentration
      assayed, and concurrently promoted cell differentiation and expression of
      adhesion molecules which are known to binder the spreading ability of cancer
      cells. The positive effect of relaxin on MCF-7 cell differentiation was even
      enhanced when these cells were cocultured with myoepithelial cells, thus
      recreating a microenvironment reminiscent of the tissue architecture of the
      mammary ducts in vivo. Concerning the mechanisms of action of relaxin on MCF-7
      cells, it seems that the growth-inhibiting and differentiation-promoting effects
      of the peptide are mediated through the activation of the synthetic pathway of
      nitric oxide.

PMID- 9180843
TI  - [Mutations of the androgen receptor gene a possible role in prostate cancer].
AB  - Prostate cancer is the second most frequent cancer in men, and the first after 75
      years of age. It is androgen dependent and modifications of the androgen receptor
      (AR) could therefore be involved in its apparition, progression and evolution
      towards a stage of androgen independence which always occurs. Mutations of the AR
      have indeed been described. Some result in a more active receptor (constitutive
      mutations, amplification of the AR gene expression, prevalence of shorter alleles
      in exon 1) and could therefore be responsible for the progression of the disease
      in the absence of androgens or the increased cancer risk in some populations.
      Other mutations, in the ligand binding domain, modify the AR specificity
      resulting in its activation by weak androgens or even antiandrogens, progestagens
      or estradiol. These mutations could also explain why prostate cancer progresses
      in the absence of androgens. On the other hand, mutations resulting in androgen
      insensitivity could explain why a significant number of prostate cancer remain
      latent and never develop into an aggressive tumor. Finally, exon 1 polymorphism
      could be used as a prognostic marker, as it has been shown that the shorter
      alleles result in a more active AR and are predominant in populations at higher
      risk for prostate cancer. At any rate, even if AR mutations may be more frequent
      than initially thought, they remain rare and their significance remains to be
      determined.

PMID- 9180844
TI  - [Laryngeal cancer and conservative treatment. Place of combined radiotherapy
      chemotherapy and modified fractionation radiotherapy].
AB  - For patients with early stages of laryngeal carcinomas, the local therapeutic
      modalities of surgery and/or radiation are the accepted standards of treatment.
      Recently, combined chemotherapy-radiotherapy and new fractionation schedules have
      received much attention as an alternative to surgery in patients with resectable
      locally advanced cancer of the larynx to preserve the larynx function. This
      article is intended to update the reader on the most recent articles written
      about the treatment of laryngeal carcinomas. The different points are: the
      results of conventional radiotherapy, the importance of parameters of
      radiotherapy (dose, fractionation, overall treatment time), new fractionation
      schedules, combined chemo-radiotherapy, randomized trial results.

PMID- 9180845
TI  - [Development of the occupational carcinogen legislation in the European
      Community].
AB  - The aim of this study is to sum up the development of European Community
      legislation concerning occupational carcinogens. In terms of prevention, 4
      periods were studied. From 1951 to 1972, only a few texts of law were
      promulgated. From 1972 to 1984, after the ratification of the convention 139 of
      the International Labour Office, more texts were promulgated. Then, from 1985 to
      1992, the protection against occupational carcinogens increased for workers,
      especially after the specific european directive edicted in 1990. Since 1992,
      most of the countries in the European Union have included this directive in their
      legislation. In terms of compensation for occupational cancer, a recommendation
      of the European Commission stated in 1962 had already proposed a list of
      compensable diseases. Because of the diversity of compensation means, it is
      difficult for the European Community to impose a common status.

PMID- 9180846
TI  - [Angiosarcoma of the breast. Apropos of 8 cases and review of the literature].
AB  - The 8 cases of primary breast angiosarcoma which were diagnosed, treated and had
      their follow-up at the Gustave-Roussy Institute between 1954 and 1995 are
      reported. The age at presentation ranged from 32 to 68 years. In 4 patients the
      vascular nature of their mammary lesion was conspicuous by a violaceous
      discolorations of the overlying skin. No patient had enlarged ipsilateral
      axillary lymph nodes. One patient had metastases. In 2 out of 5 patients who had
      a partial surgical or fine-needle biopsy before treatment, the diagnosis was
      missed, and adequate treatment was unduly delayed. The tumor most often presents
      as an ill defined area made of dense endothelium-lined papillae. A remarkable
      picture of "soap bubbles" has been identified in 4 cases. The "meshes" of fatty
      areas appear to be reinforced as they are infiltrated by tumor cells. This
      appearance may be specific of mammary angiosarcoma. By the French Cancer Centers'
      grading system for soft tissue sarcomas in general, grade is III in 3 tumors, II
      in 2 tumors, I in 3 tumors. Five tumors were treated by total mastectomy only. In
      3 cases a total mastectomy was followed by radiation therapy to the chest wall.
      At diagnosis a chemotherapy was administered only to the patient who had
      metastases. Median disease-free survival was 9 months. Median overall survival
      was 13 months. From a review of the literature a simple mastectomy appears to be
      necessary as well as enough for local treatment. Patients with a grade III
      angiosarcoma of the breast should be included into a therapeutical trial of
      adjuvant chemotherapy for soft tissue sarcomas in general.

PMID- 9180847
TI  - [Spermatocytic seminoma. Apropos of 4 cases].
AB  - The records of 4 patients treated for a spermatocytic seminoma between 1974 and
      1993 were reviewed. We described pathological and clinical features of this
      entity of seminoma which differs from those of classic seminoma. Spermatocytic
      seminoma is an essentially non metastasizing neoplasm unless complicated by the
      rare development of a sarcomatous component or metastatic spread.

PMID- 9180848
TI  - [Leiomyosarcoma of the vagina: a rare case].
AB  - Vaginal leiomyosarcoma is unfrequent. We report on a case in a 50-year-old
      multipara patient who had presented a posterior vaginal swelling since 6 months.
      The tumor was discovered at the occasion of pains and non hemorragic discharge.
      The histological pattern of the tumor was well-differentiated spindle cell
      sarcoma with pleiomorphic areas. The immunohistochemistry confirmed the smooth
      myogenic differentiation. The treatment consisted of posterior pelvic
      exenteration extended to the vagina. The patient is alive and free of disease at
      20 months of fellow-up.

PMID- 9180851
TI  - [The French Society if Oncology].

PMID- 9180850
TI  - [The French Society of Oncology].

PMID- 9180849
TI  - [Primary angiosarcoma of the breast. Apropos of 2 cases].
AB  - We report here 2 cases of breast angiosarcoma observed at Centre Val-d' Aurelle
      of Montpellier over a period of 14 years (1980 to 1994). Based on a review of
      literature, we analyze the epidemiological, pathological, clinical, diagnostic
      and treatment aspects of this rare type of breast cancer. The difficulties of
      histological diagnosis are underlined. Mastectomy is the treatment of reference.
      Breast angiosarcoma has the worst prognosis of all mammary malignancies, with a
      mean survival of 24 months. The low histologic grade and an early diagnosis are
      the most important factors of good prognosis. The benefit of irradiation and
      chemotherapy as adjuvant therapy remains to be demonstrated.

PMID- 9180852
TI  - [Clinical research on breast cancer: can we still afford our ambitions?].
AB  - In the field of breast cancer, clinical trials are more and more difficult to
      perform. In a first part, the effectiveness of the benefits are discussed as the
      respective implication of detection and therapeutics. For the later, the recent
      metaanalysis demonstrates a tiny absolute benefit. In a second part, some
      examples studies of which can improve the life span of patients are discussed.
      Only well-designed clinical studies are able to demonstrate any advantage drawn
      from new detection programs, adjuvant treatments or quality of life end points.
      In all cases, the number of subjects for these kinds of studies is larger and
      larger. Clinical research in breast cancer is in danger because of the increased
      treatment centers, the lack of cooperative groups and official support. Proposals
      are done for a stimulation of patient accrual.

PMID- 9180854
TI  - Expression of bone matrix proteins in human breast cancer: potential roles in
      microcalcification formation and in the genesis of bone metastases.
AB  - The skeleton is the privileged target of metastatic human breast cancer cells.
      Bone metastases are indeed found in virtually all advanced breast cancer patients
      and generate major morbidity. The high osteotropism of breast cancer cells
      suggests that they exhibit a selective affinity for mineralized tissues. The
      observation that mammary malignant cells are able to induce hydroxyapatite
      crystals deposition within the primary tumour suggests that they can generate a
      microenvironment that favors the crystallization of calcium and phosphate ions
      into the bone specific hydroxyapatite. Osteonectin (OSN), osteopontin (OPN) and
      bone sialoprotein (BSP), 3 bone matrix proteins involved in bone matrix
      mineralization, are expressed in human breast cancers. BSP, an RGD (Arg-Gly-Asp)
      containing phosphoprotein, initiates hydroxyapatite deposition and mediates
      attachment of osteoclast to the same crystals prior to their resorption.
      Detection of BSP at both the protein and the mRNA levels in human breast cancer
      and in human breast cancer cell lines (MCF-7, T47-D and MDA-MB 231) indicates
      that mammary malignant cells synthesize directly BSP rather than uptaking it from
      the serum. Interestingly, the level of BSP expression correlates with the
      development of bone metastases and with poor survival. These data suggest that
      the ectopic expression of bone matrix proteins could be involved in conferring
      osteotropic properties to circulating metastatic breast cancer cells. These
      observations open new alleys of investigation for the identification of the
      molecular mechanisms responsible for the genesis of bone metastases.

PMID- 9180853
TI  - [A comparative study of 4 sequential first-line chemotherapy protocols in locally
      advanced breast cancer].
AB  - Between 1977 and 1994, our center administered successively 4 different
      chemotherapy regimens to 242 evaluable patients with locally advanced breast
      cancer. Patients with inflammatory signs were excluded. Sixty-eight patients were
      treated by AVCF (A (adriamycine) + V (vincristine) + C (cytoxan) + F (5FU)), 47
      by AECF (A + E (vindesine) + C + F), 81 by CAFP (C + A + F + P (prednisone)) and
      46 by AN (A + N (vinorelbine)). The mean number of cycle was 3. One hundred and
      twenty-five patients (52.5%) responded to chemotherapy and we recorded 35
      complete response (14.7%). The response rates at the different combinations were
      respectively: AVCF: 29.4%, AECF: 53.2%, CAFP: 64.9%, AN: 65.2%, and were
      independent of tumor size, grade and receptor status. The response rate at the
      AVCF regimen was significantly worse than the others (p = 0.0005). Breast
      conserving surgery was performed in 31 patients (14%) and 17 patients (8%) had a
      complete response. Among the 35 patients with complete response, 21 were treated
      by radiotherapy alone. Local recurrence occurred in 19 patients (7.9%) and 96
      (40%) had advanced disease. The mean follow-up of AVCF regimen was 150 months,
      115 months for AECF, 111 for CAFP and 42 months for AN. The disease-free survival
      and the overall survival were significantly better with AECF, CAFP and AN
      regimens (DFS p < 0.04, OS p < 0.02). Survival was better in those patients with
      an objective response (p = 0.002) or with non-affected axillary node at the time
      of surgery. Our study showed already that AVCF combination was significantly
      lower than AECF, CAFP, AN in terms of response rate, disease-free survival and
      overall survival. Waiting the results of randomized studies about the impact of
      neoadjuvant chemotherapy on survival, we look for chemotherapy regimen improving
      the rate of conservative surgery.

PMID- 9180855
TI  - [Tamoxifen adjuvant delays early breast cancer. Results of a cooperative
      randomized trial].
AB  - Adjuvant tamoxifen (TAM) has been proved to reduce recurrence and mortality in
      early breast cancer, nevertheless many patients did not receive TAM as adjuvant
      therapy after local treatment. In order to study the efficacy of delayed TAM
      therapy in patients who were not given immediate adjuvant hormonal treatment, a
      multicenter randomized trial has been conducted by the French National Cancer
      Centers (FNCLCC). According to eligibility criterias all women with breast cancer
      who received curative local treatment at least 2 years before (surgery +/-
      radiotherapy) with or without adjuvant chemotherapy but no hormonal treatment
      could have been included. Between September 1986 and October 1989, 494 women were
      randomized to receive either TAM 30 mg/day for 5 years or no treatment. Patients'
      characteristics such as age, tumoral stage, number of positive nodes, receptors
      status and time from local treatment were equally distributed in the 2 groups. An
      improvement in the disease free survival in the TAM treated patients can be
      observed with a significative difference (p = 0.05), nevertheless the overall
      survival is not improved in the TAM group. In the same way, in nodes positive
      patients although no significative improvement in the overall survival can be
      observed, a significative improvement in the disease free survival (p = 0.05) can
      be noted. In estradiol receptors positive patients tamoxifen gives a
      significative reduction in the odds of death (p = 0.04) and recurrence (p =
      0.03). The disease free improvement seems to be limited to 50 and more years old
      patients. The first results of this trial lead to prescribe tamoxifen to all
      postmenopausal women previously treated for an early breast cancer without
      adjuvant tamoxifen treatment.

PMID- 9180856
TI  - [First-line chemotherapy in operable breast neoplasms: results of 3 protocols].
AB  - In order to avoid modified radical mastectomy, a neoadjuvant approach was adopted
      in our institute for operable bulky breast cancers. From January, 1982, to
      December, 1995, 288 patients received primary chemotherapy with 3 different
      regimens (all doses mg/m2): (1) AVCF/AVCFM, 167 patients (adriamycin 30,
      vincristine 1 d1, cyclophosphamide 300, fluorouracil 400 d2-d5 and methotrexate
      20 d2 and d4, every 28 days); (2) NEM, 78 patients (vinorelbine 25, epirubicin
      35, methotrexate 20 d1 and d8, every 28 days); and (3) TNCF, 43 patients (THP
      adria 20, d1-d3, vinorelbine 25 d1 and d4, cyclophosphamide 300, fluorouracil 400
      d1-d4, every 21 days). Evaluation of the response comprised 3 methods: clinical
      (C), echographic (E), mammographic (M). The overall objective response rate (C:
      63/90/93; E: 49/61/85; M: 53/65/83%) is higher with regimens (2) and (3). The
      complete response rate was increased 2-fold with TNCF but the hematologic
      toxicity was very superior with this combination. Patients were all operated for
      (2) and (3), only several for (1), and the breast conservation rate (68/83/79%)
      was quite similar in the 3 regimens. The pathological complete response rate
      reached 23% with TNCF. However the impact on patient survival has to be
      confirmed.

PMID- 9180857
TI  - [Glutathione S-transferase mu 1 (GSTM1): susceptibility gene of breast cancer].
AB  - Glutathione S-transferases mu (GSTM) are dimeric cytosolic isoenzymes. They
      catalyze glutathione conjugation upon a large variety of electrophiles as
      carcinogens, trans-stilbene peroxide or benzo(a)pyrene. The gene GSTM1 is
      localized on chromosome 1p13, it has drawn attention because it is absent
      approximately in 50% of the white population. GSTM1 null genotype seems linked
      with susceptibility to cancers as lung, colon and bladder cancers. We have
      studied GSTM1 genotype from 373 primary breast tumours. The GSTM1 null genotype
      was found in 50% of the cases (185/373). The incidence study of GSTM1 copy number
      on clinical and biological variables displayed a significant difference (p <
      0.01) of the GSTM1 genotype, showed by the tumour, according to the patient age
      at diagnosis. The patients younger than 55 years had a percentage more important
      of primary tumours (65%) with a copy number of GSTM1 gene, inferior or equal at
      one, compared to the patients older than 55 years (52%). The tumours, whose
      cathepsin D level was high, presented few copies of GSTM1 gene (p < 0.03). There
      was no other relationship, particularly, with tumour size, node status,
      histological type, hormonal receptors, pS2 cytosolic level GSTM1 gene seems
      protect the mammary gland from cancerogenesis with its detoxification role. This
      results had not, pointed out in breast cancer, yet.

PMID- 9180859
TI  - [Hepatic resection for breast cancer metastasis. The concept of adjuvant
      surgery].
AB  - Surgery for hepatic metastases from breast cancer remains anecdotal and
      controversial. This retrospective series of 21 patients analyses survival after
      hepatic resection. These patients presented with isolated metachronous
      metastases, controlled by systemic treatment; surgery was considered to be an
      adjuvant treatment. There was no surgical mortality. The TNM stage of the initial
      breast cancer, the time to onset of metastases and the number of hepatic
      metastases did not influence survival. The 5-year survival, after diagnosis of
      metastatic disease, was 60%; clearly better than the expected survival. Eleven
      patients are currently alive without recurrence. Six patients developed a
      recurrence in the remaining liver after a mean interval of 12 months, including 4
      patients who died after a mean interval of 49 months. These results suggest that
      a subgroup of patients with hepatic metastases from breast cancer may benefit
      from surgical resection. This surgery must be proposed in patients with isolated
      disease progression controlled by systemic treatment. In our experience, adjuvant
      surgery of hepatic metastases from breast cancer is followed by an uneventful
      postoperative course, improves survival and, in 50% of cases, allows
      discontinuation of chemotherapy, improving the patient's quality of life.

PMID- 9180858
TI  - [Germ-line mutation of BRCA1 in patients with breast and/or ovarian cancer in
      high risk families in Northern France].
AB  - The BRCA1 gene modification is responsible for an autosomal dominant syndrome of
      inherited early onset breast and/or ovarian cancer. This gene is estimated to
      account for almost half of inherited breast cancers and three quarters of
      inherited breast/ovarian cancers. This suggests that about 1 out of 500 women may
      carry BRCA1 mutation. The BRCA1 gene was isolated by positional cloning in 1994.
      More than 100 different mutations have been found in the germline of affected
      individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36
      patients treated at the Centre Oscar-Lambret for breast and/or ovarian cancer and
      that belonged to high risk families. We have found 24 mutations: 9 true mutations
      inducing modifications of the BRCA1 protein (BRCA1+), 5 mutations with unknown
      consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms
      that had been previously described. All the BRCA1+ cases had a HPG3 tumor. The
      median age of discovery and the receptor positivity percentage are lower in
      hereditary breast cancer than in the standard population of the breast cancers
      treated in our center. Consequently, BRCA1 mutations are associated to parameters
      thought to be of bad prognosis.

PMID- 9180860
TI  - [Endometrial cancer and tamoxifen. Discussion apropos of a series of cases].
AB  - Tamoxifen is widely used nowadays in the management of breast cancer, having
      established its efficacy in this indication, especially for postmenopausal
      patients with ER-positive breast tumours. However, tamoxifen has recently been
      recognized as carcinogenic for the human endometrium, probably with an effect of
      duration of treatment. Moreover, this drug may be associated with the occurrence
      of endometrial cancers of unusual histological types and/or of a more aggressive
      nature. We describe a case series of 11 patients who developed such cancers after
      having previously received tamoxifen for breast cancer. Several assumptions on
      the mechanisms underlying the attributed carcinogenic properties of tamoxifen,
      for the endometrium and potentially for other organs, are discussed on the basis
      of current knowledge.

PMID- 9180861
TI  - [Vaccination against the tumoral mammary epithelial cells expressing MUC1 mucin].
AB  - Polymorphic epithelial mucin (PEM), encoded by the MUC1 gene, is present at the
      apical surface of glandular epithelial cells. It is both overexpressed and
      aberrantly glycosylated in the majority of breast tumors, resulting in an
      antigenically distinct molecule and a potential target for immunotherapy trials.
      This transmembrane protein is cleaved into the circulation where it is detectable
      as a tumour marker (CA15.3) by a variety of antibodies, allowing for early
      detection of recurrences as well as evaluation of treatment efficacy. We shall
      review here the molecular structure of this protein at the basis for its
      immunogenicity and discuss preclinical and clinical trials in progress using
      immunogens based on MUC1. We shall also briefly review the altered immune
      reactivity in cancer patients.

PMID- 9180862
TI  - [Current aspects in histopathological assessment of breast cancer].
AB  - Histopathological evaluation of breast cancers implies currently not only the
      assessment of the classical diagnostic and prognostic criteria, but also that of
      biological parameters. The importance in medical practice of some of these
      parameters (oestrogen receptors, proliferation index) is widely accepted, whereas
      the significance of others (p53, c-erb B-2, tumoral angiogenesis) is still
      controversial. Immunohistochemistry is both a reliable and simple method for the
      evaluation of these parameters in so far the indications of this analysis are
      accurate and the technical procedures well defined.

PMID- 9180863
TI  - [Molecular aspects of different mechanisms of tamoxifen resistance].
AB  - Tamoxifen is the most currently used antiestrogen in the endocrine treatment of
      breast cancer. However, despite a small proportion of estrogen receptor positive
      tumors presenting de novo resistance to treatment, numerous tumors develop
      acquired resistance after a first phase of response. Many mechanisms have been
      proposed, but none could be identified as a real explanation of these phenomena
      of resistance. The hypotheses suggested are related to the series of events
      implied in the transduction of the signal following the ligand binding to
      estrogen receptor and concerning several levels: (1) loss or mutation of the
      estrogen receptor; (2) modification in estrogen receptor associated parameters;
      (3) alteration in the estrogen response element; (4) high levels of antiestrogen
      binding sites; (5) alteration of metabolism or availability of tamoxifen. The
      tamoxifen resistance certainly concerns several of these mechanism. Therefore, it
      is necessary to go on studying these mechanisms and to elucidate the connections
      existing between all of them.

PMID- 9180864
TI  - [Imaging of breast neoplasms].
AB  - Imaging is crucial in early diagnosis of breast cancer. Mammography is still the
      most simple and reproducible method, except in dense breast. In these
      circumstances, ultrasonography may be helpful. Magnetic resonance imaging has
      some indications such as the diagnosis of local relapses and preoperative
      staging.

PMID- 9180865
TI  - [Somatic genetics of breast cancer].
AB  - Genetic events involved in breast tumor formation are described. Abnormalities
      known point to determine the genes which participate in tumorigenesis. Mechanisms
      involved should be oncogene activation, tumor suppressor gene inactivation,
      abnormal protein expression. Multiple genetic alterations are probably necessary
      for a normal tissue to become malignant. Most of these genetic alterations seem
      to be somatic. Only 1 or 2 steps can be inherited and in familial cancer only (5%
      of breast cancers). Characterization of altered genes at somatic level during
      carcinogenesis will allow progress in the understanding of the molecular
      mechanisms involved and in the use these genetic markers in clinical oncology.

PMID- 9180866
TI  - [Dose intensification of adjuvant chemotherapy in high-risk non-metastatic breast
      cancer: a critical review].
AB  - Dose intensification with or without hematopoietic support, tries to overcome
      resistance of breast cancer to conventional treatment. Rationale of this approach
      mainly is: (1) the existence of a dose response and/or a dose-intensity-effect
      relationships; (2) the selection of high-risk and chemosensitive patient
      population, with a low tumor burden at the time of dose intensification. Progress
      in supportive therapy has reduced the toxicity of dose intensification. The
      apparent benefit observed in pilot studies may be, in part, due to patient
      selection bias and definitive evaluation of the efficacy has to be addressed by
      prospective controlled trials. This article overviews rationale, main therapeutic
      results and future prospects with a critical viewpoint.

PMID- 9180867
TI  - [Indications for magnetic resonance imaging in pneumology].
AB  - Tissue mobilization caused by respiration and heart beat and lower spacial
      resolution than with computed tomography has limited use of magnetic resonance
      imaging (MRI) in pneumology. Nevertheless, because of the high-quality of
      spontaneous contrast and the non irradiation nature of the examination, there are
      selected indications. For bronchogenic cancer, MRI is reserved for selected cases
      to evaluate tumor extension. For tumors of the mediastinum, MRI is particularly
      useful for evaluating extension of neurogenic tumors. MRI also gives a better
      visualization of processes involving the diaphragm than computed tomography. The
      development of magnetic resonance angiography is a major progress for exploration
      of pulmonary embolism as repeated acquisitions can be obtained without injection
      of a contrast medium. Several studies have shown that MRI visualizes well
      solitary lung nodules, clearly distinguishing fat content from vascularized
      nodules. For the pulmonary parenchyma, further advances are necessary before MRI
      can become a routine exploration technique.

PMID- 9180868
TI  - [Nutrition in patients treated with antilipemic agents. Survey of 337 patients].
AB  - OBJECTIVE: Assess eating habits in patients with dyslipidemia taking lipid
      lowering drugs and compare the current situation with generally proposed
      counselling. METHODS: In the framework of a survey on the prevention of
      cardiovascular risk, we studied eating habits in 337 subjects. Food intake was
      recorded for 3 consecutive days and data compared among groups of subjects taking
      different classes of lipid-lowering drugs. RESULTS: Lipid-lowering therapy was
      relatively effective, giving satisfactory laboratory results. In general,
      patients followed general counselling concerning hyperlipidemia. However, for
      more specific aspects such as balanced fatty acid intake, and elements aimed at
      mid-term prevention, results could still be improved by further explaining
      desirable eating habits. CONCLUSION: For patients with hyperlipidemia, it is
      clear that personalized counseling management, in a structured health care unit,
      is certainly the best way to help these patients and optimize therapeutic
      results.

PMID- 9180869
TI  - [Circadian rhythm in myocardial infarct in France. Results of the USIK study].
AB  - OBJECTIVES: To analyze the circadian pattern of the first signs of myocardial
      infarction in France. METHODS: The USIK study was conducted in November 1995
      among patients hospitalized in cardiac intensive care units within 48 hours after
      the first signs of confirmed myocardial infarction. This prospective study
      recorded the day and hour of onset for each eligible patient. RESULTS: Three
      hundred seventy-three centers throughout France participated, including 2563
      patients (71% men), mean age 68 years, with confirmed myocardial infarction. The
      day of the week in which the first signs occurred was recorded between November 3
      and 30, 1995. The pattern did not show any peaks, notably on Monday as reported
      in the literature. The hour of onset was known in 2468 patients (96.3%).
      Demographic features and past history did not vary for the overall population.
      Hour of onset was: between midnight and 6 a.m. 20.1%; between 6 and 12 a.m.
      30.6%; between noon and 6 p.m. 25.7%; between 6 p.m. and midnight 23.6% (p <
      0.001). This pattern was also studied in several subgroups of patients defined by
      age, sex, presence or absence of different cardiovascular risk factors or
      pertinent cardiovascular history. Univariate analysis showed that the
      distribution in the 6 a.m.-noon period was significantly different by age group.
      Older patients had a higher morning peak than younger patients (32.6% versus
      28.7%; p = 0.03). Inversely, this peak was lower in smokers compared with non
      smokers (26.7% versus 32.4%; p = 0.005); likewise, in patients with recurrent
      infarction compared with first infarction patients (24.7% versus 31.9%; p =
      0.003). Other variables did not affect the circadian pattern. After multivariate
      analysis, only 2 of these 3 factors had an influence on distribution in the 6-12
      a.m. period: smoking habits (odds ratio = 0.75; p < 0.01) and prior myocardial
      infarction (odds ratio = 0.70; p < 0.01). CONCLUSION: This large epidemiology
      study confirms that there is a morning peak in the circadian pattern of
      myocardial infarction in France. Smoking and past history of infarction
      significantly affect the circadian pattern.

PMID- 9180870
TI  - [Severe recurrent hypoglycemia disclosing anorexia nervosa].

PMID- 9180871
TI  - [Takayasu disease and ankylosing spondylarthritis: a probably non-fortuitous
      association].

PMID- 9180872
TI  - [An equivalent of anti-androgen withdrawal syndrome: decrease of prostate
      specific antigen and clinical response to estramustine phosphate withdrawal].

PMID- 9180873
TI  - [Absence of cerebral lymphoma in chronic Epstein-Barr virus encephalitis in a
      patient with HIV infection].

PMID- 9180874
TI  - [New therapeutic strategies in HIV infection].

PMID- 9180875
TI  - [Lymph node hypertrophy during antitubercular treatment. A paradoxic phenomenon].

PMID- 9180876
TI  - [Bronchial asthma. Physiopathology. Classic conception and new concepts].

PMID- 9180877
TI  - [Bronchial asthma. Long-term treatment].

PMID- 9180878
TI  - [Bronchial asthma; Therapeutic management of acute severe asthma in adults
      (excluding mechanical ventilation)].

PMID- 9180879
TI  - [Gougerot Sjogren syndrome and hepatitis C virus: what relation?].
AB  - The incidence of Sjogrens syndrome (SS) in patients with chronic liver disease
      and that of hepatitis C in mixed cryoglobulinemia strongly-suggest a link between
      the hepatitis C virus (HCV) and SS. A recent report has also demonstrated typical
      lymphocyte sialadenitis in HCV-positive subjects, raising a question concerning
      the classical definition of SS. Do patients with HCV and lymphocyte sialadenitis
      have SS? If the problem of variable diagnostic criteria can be overcome (for
      example by using the criteria established by the European study group) it can be
      concluded that the proportion of HCV+ patients with SS is related to female sex,
      age (perimenopause period in women), and liver histology rather than fibrosis,
      but not with duration of the liver disease, nor cirrhosis or viral genotype. The
      second question is to determine whether the observed focal lymphocyte
      infiltration of the salivary glands is typical of SS. As routine biopsy results
      lack specificity and sensitivity, immunohistochemistry is required to identify T8
      predominance distinctive of SS. Results obtained to date suggest that the T8
      sialadenitis might result from an autoimmune mechanism and consequently that the
      SS-HCV association might either be a coincidence between the two relatively
      frequent diseases or on the contrary that HCV plays a pathogenic role in SS. The
      major argument for the latter hypothesis would be the demonstration of HCV within
      the salivary gland epithelial cells. As HCV-positive immunohistochemistry tests
      on salivary biopsies may simply indicate presence of HCV in the blood stream at
      the time of biopsy, more sophisticated in situ PCR methods are currently being
      applied in an attempt to obtain objective evidence which could incriminate HCV
      infection of the salivary glands as a causal agent in Sjogrens syndrome.

PMID- 9180880
TI  - [Central venous catheters. Prospective surveillance of a hospital].
AB  - OBJECTIVES: All the central venous catheters (CVC) inserted at the Saint-Antoine
      Hospital between December 5, 1994 and June 6, 1995 were prospectively studied in
      order to better define practices in the management of CVC and to determine the
      rate of catheter-related infections. METHODS: The following data were recorded
      for each CVC: insertion procedure, clinical data, catheter dressings, removal,
      catheter-related infections, bacteriological findings. Catheter-related
      infections were distinguished from probably catheter-related infections and
      localized skin infections. RESULTS: Among 325 patients, a total of 414 catheters
      were inserted. At the end of the surveillance period, 350 (85%) had been removed,
      43 (10%) were still in place and 21 (5%) were lost to follow-up. Analysis of
      procedures such as cutaneous disinfection, routine replacement of the i.v. sets
      or changes of dressings showed wide variations between care units and within the
      same unit. The overall incidence of catheter-related infections was 0.24 per 100
      days of catheterization. Infections occurred 29 +/- 34 days after insertion.
      Microorganisms responsible for catheter-related bacteremia were mostly Gram
      positive (84%) and Gram negative (16%). Sixty-two infections (15%) were
      clinically suspected by physicians, leading to the catheter removal in 84% of
      cases. Out of the 43 CVC sent to the laboratory, 29 (67%) were negative (i.e.,
      "sterile") in quantitative culture of the tips as described by Brun-Buisson,
      suggesting that the CVC was unnecessarily removed. Bacteriological analysis
      ordered by physicians were not always relevant. For example, 76% of CVC received
      by the laboratory were systematically sent although they were not suspected of
      infections. Conversely, only 61% of exsudate formation at the insertion site were
      collected and analyzed. CONCLUSION: This study was designed to recall good
      guidelines to the hospital staff. Results will lead to the development of a
      better use of antiseptics and to the implementation of appropriate and
      standardized procedures to reduce risk infection.

PMID- 9180881
TI  - [Hydatid cyst of the heart].
AB  - BACKGROUND: We report an unusual localization of a hydatid cyst: the septum
      interventriculare. CASE REPORT: A 60-year-old algerian man with hypertension was
      treated for cardiac insufficiency with hypereosinophilia. Cardiac echography
      showed a round tumor in the septum interventriculare. Serologic tests for
      hydatidosis were positive. Computed tomography and magnetic resonance imaging
      were consistent with the diagnostic of hydatid cyst. Surgical treatment was
      rejected because of severe underlying hypertensive cardiopathy. DISCUSSION:
      Cardiac hydatidosis is uncommon, but may be revealed by cyst rupture. Treatment
      requires surgery and associated medical management with albendazole requires
      further evaluation.

PMID- 9180882
TI  - [Hepatic granulomatosis associated with a circulating anticoagulant, disclosing Q
      fever].

PMID- 9180883
TI  - [Drug allergies: value of the leucotriene C4 release test?].

PMID- 9180884
TI  - [Splanchnicectomy under videothoracoscopy].

PMID- 9180885
TI  - [E. Multilocularis infection under treatment with albendazole for very long
      durations].

PMID- 9180886
TI  - [Screening for cancer of the cervix. New realistic and acceptable dispositions,
      but quality remains the necessary counterpart for smears every 3 years].

PMID- 9180887
TI  - [Erosive nodular rheumatoid arthritis triggered by hepatitis B vaccination].

PMID- 9180888
TI  - [A case of segmentary unilateral occlusion of the central retinal vein following
      hepatitis B vaccination].

PMID- 9180889
TI  - [Insulin resistance, arterial hypertension and cardiovascular prevention.
      Therapeutic implications].

PMID- 9180890
TI  - [Cutaneous manifestations related to malignant hematologic diseases].

PMID- 9180891
TI  - [Reducing the infectious risk of labile blood products].

PMID- 9180892
TI  - Insulin stimulation of Na/H antiport in L-6 cells: a different mechanism in
      myoblasts and myotubes.
AB  - Insulin modulation of the Na/H antiport of L-6 cells, from rat skeletal muscle
      was studied in both myoblasts and myotubes using the fluorescent, pH sensitive,
      intracellular probe 2',7' bis (carboxyethyl)-5(6)-carboxyfluorescein. Insulin
      stimulated the Na/H antiport activity in L-6 cells, showing a bell-shaped dose
      response typical of other insulin responses: a maximum at 10 nM (delta pH of
      0.132 +/- 0.007 and 0.160 +/- 0.040 over basal value, for myoblasts and myotubes,
      respectively; means +/- SD, n = 6-8) and smaller effects at higher and lower
      concentrations. Phorbol 12-myristate 13-acetate (PMA), an activator of protein
      kinase C, also stimulated the antiport in myoblasts but not in myotubes.
      Surprisingly the rapid increase in intracellular pH was not observed when insulin
      and PMA were added simultaneously to myoblasts; apparently these two activators
      mutually excluded each other. Downregulation of protein kinase C, obtained by
      preincubation of cells with PMA for 20 hr, totally abolished both hormone and PMA
      effects in myoblasts, whereas in myotubes insulin stimulation was not affected.
      Inhibitors of tyrosine kinase activity, such as erbstatin analog and genistein
      abolished insulin effect on the Na/H antiport, both in myoblasts and in myotubes.
      Different sensitivity to pertussis toxin in the two cell types suggests that the
      differentiation process leads to a change in the signal pathways involved in the
      physiological response to insulin.

PMID- 9180893
TI  - Role of cadherins 5 and 13 in the aortic endothelial barrier.
AB  - We investigated the role of the cadherins 5 and 13 in the solute barrier formed
      by aortic endothelial cells in vitro. In confluent monolayers of bovine aortic
      endothelial cells, immunofluorescence with antibodies to the external domain of
      cadherin 5 (Mab 9H7) or to cadherin 13 (Mab Ec6C10) found staining for both
      cadherins at endothelial cell borders. Western blotting with an antibody to the
      characteristic cadherin cytoplasmic tail or with an antibody to the extracellular
      domain of cadherin 5 revealed a single 125 kD protein band. A second larger band
      was found at 130 kD with the anti-cadherin 13 Mab which was not recognized by an
      antibody to the cadherin cytoplasmic tail. A calcium switch strategy was used to
      investigate the involvement of these cadherins in the endothelial barrier.
      Changes in the permeability of small solutes in an endothelial cell column
      produced by a decrease in calcium concentration followed by a return to normal
      calcium, with or without antibody, were recorded. We found that anti-cadherin 5
      IgG (10 micrograms/ml) interfered with the reforming of interendothelial
      junctions after restoration of calcium at every time point tested for a total of
      45 min after restoration of calcium. The anti-cadherin 13 IgG (10 micrograms/ml)
      did not block reforming of the endothelial barrier in a similar manner. The
      presence of this antibody delayed only by 15 min the restoration of the normal
      barrier. Without calcium switch, addition of either monoclonal antibody (10
      micrograms/ml) to the endothelial cell column had no effect on solute
      permeability. These results suggest that cadherin 5 in bovine aortic endothelial
      cells has a major functional role in forming the calcium-sensitive endothelial
      junction in vitro and may play an important role in the normal structure and
      function of the in vivo barrier.

PMID- 9180894
TI  - Exogenous, basal, and flow-induced nitric oxide production and endothelial cell
      proliferation.
AB  - The role of nitric oxide (NO) from endogenous and exogenous sources in regulating
      large vessel and microvascular endothelial cell proliferation was investigated.
      Exogenous NO liberated from five different chemical donors inhibited bovine
      aortic, bovine retinal microvascular, and human umbilical vein endothelial cell
      proliferation in a dose-dependent manner as determined by 3H-thymidine
      incorporation. The potency of the donors varied as a function of the donors' half
      lives. Donors with half-lives greater than 30 min were more effective than donors
      with significantly shorter half-lives. Coincubation of endothelial cells with 0.4
      mM deoxyadenosine and 0.4 mM deoxyguanosine reduced the percentage of inhibition
      due to an NO donor. These data are consistent with a ribonucleotide reductase
      dependent mechanism of inhibition. Inhibition of basal NO production with four
      different inhibitors of nitric oxide synthase (NOS) did not modify proliferation.
      Laminar flow with a wall shear stress of 22 dyn/cm2 inhibited the proliferation
      of subconfluent bovine aortic endothelial cells. The addition of a NOS inhibitor
      did not abrogate the flow-induced inhibition of proliferation, suggesting that
      flow-stimulated release of NO from endothelial cells did not account for flow
      induced inhibition of proliferation. Taken together, these data suggest that
      relatively large concentrations of exogenous NO inhibit endothelial cell
      proliferation, while endogenous levels of NO are inadequate to inhibit
      proliferation.

PMID- 9180895
TI  - Inhibition of serine-threonine protein phosphatases decreases barrier function of
      rat pulmonary microvascular endothelial cells.
AB  - The flux of multisized fluorescein-isothiocyanate-labeled hydroxy ethyl starch
      (FITC-HES) macromolecules was used to assess changes in barrier function of rat
      pulmonary microvascular endothelial cell (RPMVEC) monolayers exposed to protein
      phosphatase (PP) inhibitors or cGMP analogs and atriopeptin (ANF). Two potent PP
      inhibitors, calyculin A (CalA) and okadaic acid (OA), increased RPMVEC
      permeability in a dose- and time-dependent manner, and CalA had a higher
      intrinsic activity than OA. In contrast, ANF and potent cGMP analogs had no
      effect on basal RPMVEC permeability. The phosphohistone PP activity contained in
      RPMVEC sonicates was inhibited by OA with an inhibition profile that suggested at
      least two components were present, with PP2A accounting for approximately 70% of
      the OA-inhibitable phosphohistone phosphatase activity. Following separation with
      heparin-Sepharose chromatography, PP activity exhibited equipotent inhibition by
      CalA and differential inhibition by OA. Differential inhibition of PP1 and PP2A
      by OA suggested that PP1 is involved in regulating RPMVEC barrier function.
      Permeabilized RPMVEC showed increased phosphorylation of several proteins in the
      presence of phosphatase inhibitors. Treatment with KT 5926, a myosin light chain
      (MLC) kinase (MLCK) inhibitor, or rolipram, a phosphodiesterase inhibitor,
      decreased 32P incorporation into immunoprecipitated MLC by CalA and OA. However,
      this effect did not abolish either the CalA- or OA-induced decrease in the RPMVEC
      barrier function. Localization of filamentous (F) actin was at the periphery as
      well as in the cytoplasm and perinuclear region, whereas nonmuscle myosin was
      seen in the perinuclear region. Neither of these patterns was changed in the
      presence of CalA. Thus, cGMP does not alter RPMVEC permeability, but inhibition
      of PP activity results in loss of barrier function by a mechanism independent
      from MLC phosphorylation.

PMID- 9180896
TI  - Smooth muscle sarcolemma-associated phospholipase C-beta 2; agonist-evoked
      translocation.
AB  - About 25% of the total cellular PLC beta 2 content was found to be associated
      with a sarcolemmal fraction (SARC) isolated from unstimulated porcine trachealis
      smooth muscle. SARC-associated PLC beta 2 was located within two compartments, a
      detergent-extractable compartment and a nondetergent extractable compartment.
      SARC PLC beta 2 was measured after extraction with 0.6 M KCI; therefore, PLC beta
      2 was not bound solely by electrostatic forces within either of these
      compartments. PLC beta 2 was shown to translocate from cytosol to SARC during a
      20-sec activation of intact muscle with a muscarinic agonist, carbachol (CARB);
      i.e., cytosolic total PLC beta 2 content decreased significantly to 73 +/- 7% of
      control and SARC total PLC beta 2 content increased to 180 +/- 15% of control
      value. This translocation was maintained at 5 min of CARB. CARB-evoked
      translocation occurred into the detergent-extractable SARC fraction, and PLC beta
      2 content in this fraction increased 300% compared with that in unstimulated
      muscle. After CARB, SARC PLC beta 2 content accounted for > 50% of total cellular
      PLC beta 2 content. CARB-evoked increase in PLC activity in SARC paralleled the
      increase in PLC beta 2 content. CARB-induced translocations of PLC beta 2 from
      the cytosol to SARC were of a similar magnitude as occurred with phorbol ester
      induced translocations of PKC alpha.

PMID- 9180897
TI  - Bacterial lipopolysaccharide reduced intestinal barrier function and altered
      localization of 7H6 antigen in IEC-6 rat intestinal crypt cells.
AB  - The intestinal epithelial barrier restricts the passage of potentially toxic
      substances into the systemic circulation and is considered to be mostly mediated
      by tight junctions, though the mechanisms involved in the regulation of
      intestinal tight junctions are not yet fully understood. In the present study, we
      examined whether bacterial lipopolysaccharide (LPS) altered the barrier function
      of tight junction and localization of tight junctional proteins, ZO-1 and 7H6
      antigen, in IEC-6 intestinal cells. Administration of LPS to the basolateral
      surface of IEC-6 cells disrupted the barrier function and caused the
      disappearance of 7H6 antigen from the cell border, whereas LPS administered to
      the apical surface altered neither the barrier function nor the localization of
      7H6 antigen in IEC-6 cells. On the other hand, the localization of ZO-1 was not
      influenced by these treatments of LPS. These results suggest that the interaction
      of LPS with the basolateral surface of intestinal epithelial cells disrupts the
      barrier function and 7H6 antigen take part in the maintenance of the barrier
      function in IEC-6 cells.

PMID- 9180898
TI  - Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF
      like growth factor and amphiregulin in cultured human keratinocyte growth.
AB  - CD9 is a protein with 4 transmembrane domains, and functions as a cell surface
      antigen. We have previously reported that CD9 functions as an up-regulator of
      membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) activity,
      which is a potent mitogen as well as a soluble HB-EGF. Anti-CD9 antibodies can
      neutralize the juxtacrine activity of proHB-EGF when both CD9 and proHB-EGF are
      coexpressed. We demonstrated here: (1) the CD9 gene was transcribed and
      translated in the cultured human keratinocytes; (2) anti-CD9 antibody inhibited
      the approximately 50% growth of human keratinocytes in culture; (3) CD9 was
      coprecipitated with proHB-EGF and membrane-anchored amphiregulin (proAR), and (4)
      the transient coexpression of CD9 with proHB-EGF or proAR in mouse L cells up
      regulated their juxtacrine growth factor activities. These results suggest that
      CD9 would make a heterodimer and/or trimer complex with proHB-EGF and proAR, and
      might cooperate with proHB-EGF and proAR for human keratinocyte growth in a
      juxtacrine manner.

PMID- 9180899
TI  - Influence of Bcl-2 overexpression on Na+/K(+)-ATPase pump activity: correlation
      with radiation-induced programmed cell death.
AB  - Bcl-2 overexpression in transfected PW cells is associated with inhibition of
      radiation-induced programmed cell death (PCD). We have previously reported that
      there is a relationship between inhibition of radiation-induced PCD and membrane
      hyperpolarization in these cells. In this article, we report that Na+/ K(+)
      ATPase pump activity, as measured by the uptake of Rubidium-86 (86Rb+), is
      significantly higher in Bcl-2 overexpressing PW cells than in control PW cells,
      and that pump activity following irradiation with doses > or = 500 cGy was
      reduced to a lesser extent in the Bcl-2 transfectants than in the control cells.
      When PW-Bcl-2 cells were incubated with a dose of ouabain (1 microM) that
      decreased pump activity significantly, but did not induce PCD, the previously
      reported protection from radiation-induced PCD associated with overexpression of
      Bcl-2 no longer existed. In order to demonstrate that reactive oxygen species
      (ROS) affected Na+/ K(+)-ATPase pump activity, cells were incubated with N-acetyl
      cysteine (NAC) prior to irradiation, or treated with the ROS generating drug
      buthionine sulphoxamine (BSO). 86Rb+ uptake was significantly higher in
      irradiated cells incubated with NAC compared to cells irradiated in the absence
      of NAC, while BSO resulted in lower levels of 86Rb+ uptake, suggesting that the
      effects of radiation on the Na+/K(+)-ATPase pump were due to ROS. Furthermore,
      the resting cell membrane potential of cells exposed to NAC were slightly
      hyperpolarized compared to control PW cells, whereas cells exposed to BSO were
      depolarized in comparison to control PW cells. In summary, this data suggests
      that Bcl-2 affects Na+/K(+)-ATPase pump activity, which is associated with the
      resting membrane potential and the level of susceptibility to radiation-induced
      PCD.

PMID- 9180900
TI  - CD44v10 expression in the mouse and functional activity in delayed type
      hypersensitivity.
AB  - We have described recently that expression of CD44 exon v10 (CD44v10) is down
      regulated upon metastasis of squamous cell carcinoma, whereas it is up-regulated
      in skin metastases of malignant melanoma. The striking regulation of CD44v10
      prompted us to generate a murine CD44v10-specific monoclonal antibody to define
      expression and possible functions of this particular CD44 variant isoform. In the
      mouse, expression of exon v10 was restricted to basal layers of the epidermis and
      squamous epithelium of the oral cavity, the esophagus, the omasum, glandular
      epithelium of the submandibular and the uterine gland, as well as subpopulations
      of bone marrow cells and activated lymphocytes. Expression started late during
      development, e.g., was not observed before day 16 of gestation and there was no
      evidence for developmental regulation of CD44v10 expression. Functional in vivo
      studies revealed that anti-CD44v10 had no effect on wound healing but inhibited
      edema and granuloma formation in delayed type hypersensitivity (DTH).
      Furthermore, lymphocyte-monocyte interactions could be inhibited by anti-CD44v10.
      Because a CD44v10 transfected tumour line did not show any distinct pattern of
      cell-matrix or cell-cell adhesion, the data point toward an involvement of
      CD44v10 in cell migration, possibly by acting as a target structure for
      cytokines/chemokines provided by the contacted partner cell.

PMID- 9180901
TI  - Na+/H+ exchanger (NHE) in the basolateral membrane is encoded by NHE-1 mRNA in
      LLC-PK1 clone 4 cells.
AB  - Several isoforms of Na+/H+ exchanger (NHE-1-5) have been identified. LLC-PK1
      clone 4 (CL4) expresses the amiloride-sensitive type of NHE predominantly in the
      basolateral membrane, which is believed to be NHE-1. It is not clear whether CL4
      expresses NHE in the apical membrane and which side of NHE is encoded by the NHE
      1 mRNA. Using acidified CL4 cells on the filter membrane, we examined Na(+)
      dependent pH recovery of the apical and basolateral membranes separately. Na+
      applied to the apical membrane recovered cell pH. Na(+)-dependent pH recovery in
      the apical membrane was not inhibited by SITS, DIDS, or contralateral amiloride.
      Li+ but not K+, chol+, or NMG+ could replace Na+. These data are consistent with
      the presence of NHE in the apical membrane. Transfection with an antisense
      oligonucleotide corresponding to the 5' terminal site of NHE-1 cDNA of CL4
      decreased NHE activity in the basolateral membrane but not in the apical
      membrane. We conclude that CL4 expresses NHE activities in both apical and
      basolateral membranes and that NHE-1 mRNA encodes NHE only in the basolateral
      membrane.

PMID- 9180902
TI  - Differential gene expression in SV40-mediated immortalization of human
      fibroblasts.
AB  - Normal human diploid fibroblasts (HF) have a limited life span, undergo
      senescence, and rarely, if ever, spontaneously immortalize in culture.
      Introduction of the gene for T antigen encoded by the DNA virus SV40 extends the
      life span of HF and increases the frequency of immortalization; however,
      immortalization requires both T-dependent and T-independent functions. We
      previously generated independent SV40-transformed non-immortal (pre-immortal) HF
      cell lines from which we then obtained immortal sublines as part of a
      multifaceted approach to identify functions responsible for immortalization. In
      this study we undertook a search for cellular mRNAs which are differentially
      expressed upon immortalization. A lambda cDNA library was prepared from a pre
      immortal SV40-transformed HF (HF-C). We screened the library with a subtracted
      probe enriched for sequences present in HF-C and reduced in immortal AR5 cells. A
      more limited screen was also employed for sequences overexpressed in AR5 using a
      different strategy. Alterations in the level of mRNAs in AR5 encoding functions
      relevant to signal transduction pathways were identified; however, most cDNAs
      encoded novel sequences. In an effort to clarify which of the altered mRNAs are
      most relevant to immortalization, we performed Northern analysis with RNA
      prepared from three paired sets of independent pre-immortal and immortal (4 cell
      lines) SV40-transformants using eight cloned cDNAs which show reduced expression
      in AR5. Three of these were reduced in additional immortal cell lines as well;
      one, J4-4 (unknown function) is reduced in all the immortal cell lines tested; a
      second, J4-3 (possible PP2C type phosphatase) is reduced in 2 of the 3 matched
      sets; and a third, J2-2 (unknown function) is reduced in 2 unrelated immortal
      cell lines. Although the roles of these genes are as yet unclear, their further
      analysis should extend our understanding of the molecular bases for
      immortalization. In particular, the patterns of expression of J4-4 and J4-3
      strongly suggest that they are involved in the process of immortalization and/or
      can serve as target genes for assessing regulators of gene expression in this
      process.

PMID- 9180904
TI  - Growth factor receptor expression during in vitro differentiation of partially
      purified populations containing murine stem cells.
AB  - We have investigated, by semiquantitative RT-PCR, the kinetics of activation of
      hematopoietic receptors and differentiation markers in partially purified murine
      hematopoietic stem cells (HSC) induced to differentiate in serum-free culture
      with combinations of growth factor (GF). The combinations of GF used sustained
      either multilineage [stem cell factor (SCF) + interleukin 3 (IL-3), or erythroid
      [SCF + IL-3 + erythropoietin (Epo)] or myeloid [SCF + IL-3 + granulocyte colony
      stimulating factor (G-CSF)] differentiation. The GF receptor genes investigated
      were the alpha and beta subunits of the IL-3 and granulocyte-macrophage colony
      stimulating factor (GM-CSF) receptor, the erythropoietin receptor, the G-CSF
      receptor, and c-Fms, the receptor for macrophage colony-stimulating factor (M
      CSF). The expression of Gata1 and alpha- and beta-globin was investigated at the
      same time as a marker of erythroid differentiation. HSC were purified according
      to standard protocols, which include partitioning of lineage-negative bone marrow
      cells with the mitochondrial dye Rhodamine 123 (Rho) into Rho-dull (> or = 17% of
      which reconstitute long-term hematopoiesis in recipient mice) and into Rho-bright
      (which are as capable as Rho-dull of multilineage differentiation but do not
      permanently reconstitute the host). The following pattern of expression was
      observed: the alpha subunit of the IL-3 receptor clearly was expressed in both
      Rho-bright and Rho-dull cells at the outset, and its expression did not change
      over time in culture. The beta subunits of the IL-3 and GM-CSF receptor, the
      alpha subunit of the GM-CSF receptor, the Epo and G-CSF receptors and Fms barely
      were expressed in purified Rho-bright and Rho-dull cells, but their expression
      increased in cells cultured both in erythroid and in myeloid GF combinations.
      Gata1 was expressed maximally in Rho-bright cells but was below the level of
      detection in Rho-dull cells. Rho-dull cells expressed Gata1 when cultured both in
      erythroid and in myeloid GF combinations. In contrast, alpha- and beta-globin,
      which also were not expressed in the purified cells, were induced only in cells
      stimulated with Epo. These results indicate that the genes for all the GF
      receptors investigated (with the exception of the alpha subunit of the IL-3
      receptor) are expressed at low levels, if any, in purified Rho-bright or Rho-dull
      cells, but are expressed in their progeny cultured either in erythroid or myeloid
      GF combinations. The expression of the Epo receptor, in particular, is activated
      both in erythroid (alpha- and beta-globin positive and in myeloid (alpha- and
      beta-globin negative) cells. Therefore, activation of the expression of the Epo
      receptor gene and activation of the erythroid differentiation program are two
      independent events in normal hematopoiesis.

PMID- 9180903
TI  - Adenosine inhibits DNA synthesis stimulated with TSH, insulin, and phorbol 12
      myristate 13-acetate in rat thyroid FRTL-5 cells.
AB  - Adenosine has been shown to modulate cell proliferation in FRTL-5 thyroid cells,
      although the mechanisms by which this interaction occurs is still unclear. In the
      present study we investigated the effects of adenosine on the 3H-thymidine
      incorporation, cell cycle kinetics, and expression of the transcription factor c
      Fos in cells stimulated via three different mitogenic pathways, i.e., by thyroid
      stimulating hormone (TSH) [adenosine 3',5'-cyclic monophosphate(cAMP)], insulin
      (tyrosine kinase), or phorbol 12-myristate 13-acetate (protein kinase C).
      Addition of adenosine to cells grown in medium containing hormones and serum did
      not inhibit the incorporation of 3H-thymidine. If adenosine was added to hormone
      deprived cells together with any of the tested mitogens, the stimulation of the
      3H-thymidine incorporation was inhibited in a dose-dependent manner. The
      inhibition was significantly lower when the cells were preincubated with TSH or
      insulin for 48 h. Flow cytometric studies showed that adenosine evoked an
      inhibition of the cells in the G0/G1 phase. Submaximal doses of adenosine (10 nM
      10 microM) were able to induce c-Fos expression in FRTL-5 cells. However, the
      mitogen-induced expression of c-Fos was not reduced by maximal dose of adenosine
      (100 microM). The effect of adenosine on DNA synthesis was not dependent on
      pertussis toxin-sensitive G-proteins. In addition, adenosine A1- or A2- receptor
      antagonists did not block the effect of adenosine. The effect of adenosine was
      abolished by treatment of the cells with adenosine deaminase, suggesting that the
      observed effect was not mediated by a metabolite of adenosine. The results
      suggest that adenosine is an effective blocker of mitogen-evoked DNA synthesis of
      FRTL-5 cells, provided that adenosine is administered simultaneously with the
      mitogen.

PMID- 9180905
TI  - A-ring analogues of 1, 25-(OH)2D3 with low affinity for the vitamin D receptor
      modulate chondrocytes via membrane effects that are dependent on cell maturation.
AB  - 1,25-(OH)2D3 (1,25) and 24,25-(OH)2D3(24,25) mediate their effects on
      chondrocytes through the classic vitamin D receptor (VDR) as well as through
      rapid membrane-mediated mechanisms, which result in both nongenomic and genomic
      effects. In intact cells, it is difficult to distinguish between genomic
      responses via the VDR and genomic and nongenomic responses via membrane-mediated
      pathways. In this study, we used two analogues of 1,25 that have been modified on
      the A-ring (2a, 2b) and are only 0.1% as effective in binding to the VDR as 1,25,
      to examine the role of the VDR in the response of rat costochondral resting zone
      (RC) and growth zone (GC) chondrocytes to 1,25 and 24,25. Chondrocyte
      proliferation ([3H]-thymidine incorporation), proteoglycan production ([35S]
      sulfate incorporation), and second messenger activation (activity of protein
      kinase C) were measured after treatment with 10(-8) M 1,25, 10(-7) M 24,25, or
      the analogues at 10(-9)-10(-6) M. Both analogues inhibited proliferation of both
      cell types, as did 1,25 and 24,25. Neither 2a nor 2b had an effect on
      proteoglycan production by GCs or RCs. 2a caused a dose-dependent stimulation of
      protein kinase C (PKC) that was not inhibited by cycloheximide or actinomycin D
      in either GC or RC cells. 2b, on the other hand, had no effect on PKC activity in
      RCs and only a slight stimulatory effect in GCs. Both cells produce matrix
      vesicles, extracellular organelles associated with the initial stages of
      calcification, in culture that are regulated by vitamin D metabolites. Since
      these organelles contain no DNA or RNA, they provide an excellent model for
      studying the mechanisms used by vitamin D metabolites to mediate their nongenomic
      effects. When matrix vesicles were isolated from naive cultures of growth zone
      cells and treated with 2a, a dose-dependent inhibition of PKC activity was
      observed that was similar to that found with 1,25-(OH)2D3. Plasma membranes
      contained increased PKC activity after treatment with 2a, but the magnitude of
      the effect was less than that seen with 1,25-(OH)2D3. Analogue 2b had no affect
      on PKC activity in either membrane fraction. When matrix vesicles from resting
      zone chondrocyte cultures were treated with 24,25-(OH)2D3, a significant decrease
      in PKC activity was observed. No change in enzyme activity was found for either
      1,25-(OH)2D3 or the analogues. PKC activity in the plasma membrane fraction,
      however, was increased by 24,25-(OH)2D3 as well as by analogue 2a. This study
      shows that these analogues, with little or no binding to the vitamin D receptor,
      can affect cell proliferation and PKC activity, but not proteoglycan production.
      The direct membrane effect is analogue specific and cell maturation dependent.
      Further, by eliminating the VDR-mediated component of the cellular response, we
      have provided further evidence for the existence of a membrane receptor(s)
      involved in mediating nongenomic effects of vitamin D metabolites.

PMID- 9180906
TI  - Report of the Histiocyte Society workshop on "Central nervous system (CNS)
      disease in Langerhans cell histiocytosis (LCH)".

PMID- 9180907
TI  - Analyses of prognostic factors in a retrospective review of 92 children with
      ependymoma: Italian Pediatric Neuro-oncology Group.
AB  - The principal aim of this report is to present the results of multivariate
      analyses conducted to identify clinical prognostic factors in 92 children aged <
      16 years with ependymoma (EPD) retrospectively collected in seven Italian
      centres. They were treated over a 16-year period (1977-1993). Treatment
      modalities varied. Surgery and radiotherapy (RT) was the "gold standard"
      management method for the majority of these children. Only in the late 1980s did
      some of them receive chemotherapy (CT), mainly with vincristine, lomustine (CCNU)
      and prednisone. The median follow-up of the entire study population is 36 months
      (average 43 months; range 12 to 214 months). The 10-year overall (OS) and the
      progression-free survival (PFS) of the study population were 55.5% (CI 41.4
      69.4%) and 34.7% (CI 21.4-47.8%), respectively. Age (< 5 years; > 5 years), sex,
      site (infratentorial vs. supratentorial), histology (anaplastic/malignant vs. non
      anaplastic/non-malignant), type of resection (complete vs. incomplete); use and
      fields of RT, and of CT employed were entered in a multivariate regression model
      to test their impact on OS and PFS. On univariate analysis, radical surgery, the
      use of RT and age more than 5 years at the time of diagnosis achieved
      statistically significant values for predicting long-term OS and PFS. Histology
      reached marginal statistical significance but only for PFS. When those variables
      were entered in a multivariate analysis only radical resection (P = 0.00142 and
      0.0001) resulted a significant factor for predicting long-term OS and PFS, while
      the use of RT reached a marginal statistical significance, but only for PFS (P =
      0.05). Children who had the tumour completely resected did significantly better
      than all the others who had less than a complete resection, with a 10-year OS and
      PFS for the two groups of patients of 69.8% (CI 53-86.5%) and 57.2% (CI 40.3-75%)
      and of 32.5% (CI 8.5-57.6%) and 11.1% (0-24.4%), respectively. These findings
      suggest that, for childhood EPD, radical resection should be pursued as much as
      reasonably possible. Thus, it seems justified proposing for future trials,
      patient stratification by entity of surgical resection.

PMID- 9180908
TI  - Systematic approach for detection of endocrine disorders in children treated for
      brain tumors.
AB  - Endocrine dysfunction can be challenging to diagnose in children treated for
      brain tumors. Treatments are available for hormonal replacement and when
      necessary, hormonal suppression. Without these endocrine treatment regimens, life
      can be unnecessarily difficult or unpleasant. An endocrine survey can be used to
      screen at-risk neuro-oncology patients once or twice a year to facilitate the
      recognition of endocrine dysfunction. It is hoped that through the use of a
      routine screening program, physicians will be able to diagnose and begin
      treatment of endocrine problems in a time-efficient manner.

PMID- 9180909
TI  - Animal model of human medulloblastoma: clinical, magnetic resonance imaging, and
      histopathological findings after intra-cisternal injection of MHH-MED-1 cells
      into nude rats.
AB  - To establish an animal model of human medulloblastoma, we have injected human MHH
      MED-1 cells into the cisterna magna of nude rats. Tumors grew in 3 out of 4
      animals injected with 10(6) medulloblastoma cells. Affected animals showed little
      or no weight gain and eventually lost weight but did not develop obvious
      neurological symptoms until the end of observation on day 31 after inoculation.
      At this time, magnetic resonance imaging (MRI) in tumor-bearing rats revealed
      contrast enhancement in the region of the fourth ventricle and the cisterna
      magna. Neuropathological examination demonstrated corresponding leptomeningeal
      growth in the cisterna magna invading the medulla oblongata, and tumor growth
      within the fourth ventricle invading the pons. The tumors basically showed the
      same immunostaining pattern as MHH-MED-1 cells in vitro expressing neuron
      specific enolase (NSE) and vimentin, but no neurofilaments (NFs), synapthophysin,
      or glial fibrillary acidic protein (GFAP). No tumor grew in the fourth animal,
      which had a normal weight gain and no alteration on MRI. In conclusion (1) the
      intrathecally injected human medulloblastoma cells spread similar to
      medulloblastomas in patients, (2) tumor growth is readily detected by MRI, (3)
      the new animal model is a suitable tool for further experimental research
      including intrathecal therapeutic studies.

PMID- 9180910
TI  - Lymphoblast morphology in predicting leukemic meningeal relapse with low chamber
      count and lymphoblasts.
AB  - The diagnostic criteria for meningeal relapse (MR) of acute lymphoblastic
      leukemia (ALL) are a cerebrospinal fluid (CSF) chamber count of more than five
      leukocytes per microliter and a cytomorphological evaluation revealing
      lymphoblasts. A dilemma arises when confronted with a patient with a low CSF
      white blood cell (WBC) chamber count and lymphoblasts. We utilized a scoring
      system to review lymphoblast morphology in 12 such patients. A cell was defined
      as a lymphoblast if it could not be easily categorized as a lymphocyte, monocyte.
      histiocyte, or granulocyte. Each lymphoblast was scored on four parameters:
      presence of nucleoli, homogeneous distribution of chromatin, nucleocytoplasmic
      ratio greater than 75%, and nuclear irregularity. Cells were scored without
      knowledge of the patients' out come. Seven patients eventually developed MR by
      current criteria and five patients never relapsed. The mean lymphoblast scores
      for patients that did and did not relapse were 2.35 and 1.53, respectively (P <
      .001). The percent of cells scored as lymphoblasts was also significantly higher
      in patients that relapsed, 36.9% vs. 19.4% (P = .01). Our study shows that
      careful cytomorphologic analysis can predict which patients with low chamber
      counts and "blasts" on cytocentrifuge examination will progress to meningeal
      relapse. We recommend reviewing the definition of MR and using a scoring system
      when confronted with blasts in a low chamber count cerebrospinal fluid specimen.

PMID- 9180911
TI  - Carcinoma of the thyroid in children: a 25-year experience.
AB  - Over the past 25 years, 23 children with carcinoma of the thyroid have been
      treated at the Christie Hospital, Manchester. Twenty-one cases were well
      differentiated carcinoma, and two were medullary carcinoma. They were all treated
      by resection, 14 with total thyroidectomy and 9 with lobectomy or subtotal
      thyroidectomy. Sixteen children also had surgery for nodal disease. Two children
      presented with lung metastases. Sixteen children received post-operative
      radiotherapy (4 external beam, 12 131I). Median follow-up of 67 months (range 7
      233), was the same for the 21 well-differentiated carcinomas and the whole group
      including the two medullary carcinomas. All 21 children with well-differentiated
      carcinomas are alive with no evidence of progressive disease. Two relapsed after
      total thyroidectomy, but both were salvaged, one with external beam radiotherapy,
      one with 131I. One child with medullary carcinoma died with progressive disease
      after 43 months, the other is alive, but with slowly progressive disease 145
      months after diagnosis. Ten of 14 children experienced post-operative
      hypocalcaemia following total thyroidectomy, in 7 cases it persisted long-term.
      131I and external beam radiotherapy were both well tolerated. The long-term
      results of treatment of well-differentiated carcinoma of the thyroid are
      excellent, but there remains disagreement over the extent of treatment required.
      Some authors believe the condition is multifocal and requires total
      thyroidectomy, others argue that lobectomy or subtotal thyroidectomy avoids the
      possible post-operative complications of total thyroidectomy and gives equal long
      term cure rates. We agree with the latter view. Although a small series cannot be
      conclusive, we feel that our results are consistent with this. We also believe,
      that for children, radiotherapy can be reserved for relapse only, as long as
      regular follow-up is available.

PMID- 9180912
TI  - Granulocyte-macrophage colony-stimulating factor in association with high-dose
      chemotherapy (VETOPEC) for childhood solid tumors: a report from the Australia
      and New Zealand Children's Cancer Study Group.
AB  - PURPOSE: Combination chemotherapy with vincristine, etoposide, and high-dose,
      escalating cyclophosphamide (VETOPEC) is an effective regimen in pediatric
      patients with high-risk solid tumors. The toxicity of the regimen is
      predominantly haematologic. This study addressed the role of recombinant human
      granulocyte-macrophage colony-stimulating factor (GM-CSF) following each cycle of
      chemotherapy in decreasing neutropaenia, incidence of fever/ hospitalization,
      and/or increasing chemotherapy dose-intensity. PATIENTS AND METHODS: Twenty-nine
      children with recurrent solid tumors were treated with the VETOPEC regimen.
      Sequential cohorts of patients received no GM-CSF (Group I), or GM-CSF in a
      dosage of 5 micrograms/kg/day (Group II) or 10 micrograms/kg/day (Group III) on
      days 4-18 of each chemotherapy cycle. Up to four cycles of chemotherapy were
      analysed with respect to haematopoietic recovery, clinical parameters, and dose
      intensity. RESULTS: Neutrophil recovery was significantly more rapid in patients
      treated with GM-CSF. Time to achieving an absolute neutrophil count (ANC) over
      0.5 x 10(9)/L in Groups I, II, and III were 21, 18, and 16 days, respectively (P
      < 0.0001). Time to achieving an absolute neutrophil count (ANC) over 1.0 x
      10(9)/L in Groups I, II, and III were 24, 19, and 17 days, respectively (P <
      0.0001). There was no significant difference in the incidence of febrile
      neutropaenia between the three groups. Febrile neutropaenia occurred following
      42, 68, and 62% of chemotherapy cycles in Groups I, II, and III, respectively (P
      = 0.27). Chemotherapy dose intensity was not different between the three groups.
      GM-CSF was associated with pericarditis and myalgias in one patient, and
      transient hypoxia/hypotension in another. CONCLUSION: GM-CSF led to significantly
      more rapid neutrophil recovery following VETOPEC chemotherapy, but did not lead
      to any demonstrable clinical benefit, either in reducing febrile events, or in
      increasing chemotherapy dose intensity.

PMID- 9180913
TI  - Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear
      cell (PBMNC) separation in children with a body weight below 20 KG.
AB  - Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median
      13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral
      blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen
      central venous catheter (8-10 French). Separations were performed with a
      continuous flow blood separator (Fen-wall CS 3000 plus), running a specially
      adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with
      multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were
      mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body
      weight (median 16.25) subcutaneously following high-dose chemotherapy, according
      to the disease-related protocols, whereas 2 children had PBMNCS to induce graft
      vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed
      chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia
      (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was
      performed after filling the cell separator with priming solution consisting of 2
      U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl.
      In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive
      cells/kg body weight were separated; the patient who had the lowest yield was
      separated twice after another mobilizing course. Three patients (2 with
      neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double
      transplantation with 1-3 portions of the collected stem cells within a 5- to 6
      week interval. Two children had a rapid engraftment on both peripheral blood stem
      cell transplantations (PBSCTs). The third child, who had the lowest yield and was
      separated twice had prompt engraftment at the first PBSCT but delayed and
      incomplete engraftment at the second PBSCT. One patient after adoptive
      immunotransfer with PBMNCs for relapsed CML is now 40 months in complete
      cytogenetic and molecular biological remission, whereas the other patient treated
      for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate
      that PBSCS and PBMNCS can be performed in children with a body weight below 20
      kg.

PMID- 9180914
TI  - CNS late effects after ALL therapy in childhood. Part II: Conventional EEG
      recordings in asymptomatic long-term survivors of childhood ALL--an evaluation of
      the interferences between neurophysiology, neurology, psychology, and CNS
      morphology. German Late Effects Working Group.
AB  - Monitoring of therapy-related late effects after acute lymphoblastic leukemia
      (ALL) therapy in childhood has become an increasingly important area in
      posttherapeutic patient surveillance. The usefulness of conventional electro
      encephalographic (EEG) investigations as part of these attempts is
      controversially discussed. However, EEG recordings have become a popular approach
      for judgement on the functional integrity of the central nervous system in this
      subject group. The present report focuses on this problem and discusses the
      question whether and to what extent conventional EEG recordings were correlated
      with further measures of central nervous system (CNS) integrity and therapeutic
      differences. EEGs were recorded in 110 subjects, asymptomatic long-term survivors
      of ALL in childhood, during a large retrospective multicenter study evaluating
      CNS late sequelae following antileukemic therapy in Germany and Austria. EEG
      findings were correlated with demographic data, illness- and treatment-related
      parameters, as well as with data on the morphological, neurological and
      psychological status of the participating subjects. At the time of follow-up the
      EEG was abnormal in 47 cases (42.7%). The most frequent EEG abnormalities
      observed were disturbances of the background activity (n = 45, 95.8%), followed
      by hypersynchrone activities (n = 1.0, 21.3%) and interhemispheric
      differences/focal slowing (n = 6, 12.8%). With exception of age at diagnosis,
      none of the observed EEG abnormalities showed a correlation with any of the
      aforementioned illness- or treatment-related parameters. Eighty percent of the
      observed EEG abnormalities were found in children younger than 5 years at
      diagnosis. Children less than 2 years of age as well as those above 5 years at
      onset of disease showed a significantly reduced prevalence of EEG disturbances
      compared to subjects between 2 and 5 years at diagnosis. Neither the degree of
      illness nor therapy-specific differences showed any relationship to EEG outcome.
      There was no specific EEG finding for a specific morphological substrate,
      neurological or psychological deficiency and vice versa. Overall, there was no
      beneficial effect of routine EEG testing in children following therapy for ALL.
      According to our data, the evaluation of conventional EEG recordings of otherwise
      asymptomatic ALL long-term survivors is not a very helpful measure for predicting
      the degree of behavioral deficiencies, neurological disturbances, or
      morphological CNS abnormalities, which may be present or will develop in this
      special subject group.

PMID- 9180915
TI  - Therapy-related acute myeloid leukemia with t(8;21) in a child with previous
      Ewing's sarcoma.
AB  - Cases of secondary acute myeloid leukemia (AML) occurring after treatment for an
      Ewing's sarcoma are uncommon. Therapy-related AML with t(8;21) translocation is
      an entity which has been well characterized. A case of AML-2 with t(8;21) and
      t(3;15) occurring 4 years after treatment for an Ewing's sarcoma with
      cyclophosphamide, doxorubicin, vincristine, dactinomycin, and radiotherapy, is
      reported. Autologous bone marrow transplantation was performed during second
      remission, 23 months after diagnosis. Reverse transcriptase polymerase chain
      reaction of the AML1/ETO fusion gene product was performed in order to monitor
      the quality of the remission. The patient currently remains in remission 24
      months after the bone marrow transplantation.

PMID- 9180916
TI  - Application of fluorescence in situ hybridization to detect N-myc (MYCN) gene
      amplification on paraffin-embedded tissue sections of neuroblastomas.
AB  - Fluorescence in situ hybridization (FISH) was applied to neuroblastoma for
      detection of N-myc (MYCN) oncogene amplification, and the results were compared
      with Southern blot analysis (Southern). In nine neuroblastomas (formalin-fixed
      paraffin-embedded tissues were available in seven cases including two cases with
      touch preparations, and two cell lines), all five cases with N-myc amplification
      detected by Southern had cells with multiple N-myc signals by FISH, and three
      cases showed no N-myc amplification either by Southern or FISH procedure. One
      case, not examined by Southern, showed amplified signals of N-myc by FISH. These
      data indicate that FISH results for N-myc amplification have close correlation
      with Southern blot analysis. The chromosome 2-specific repetitive DNA probe was
      also applied for the analysis of ploidy by FISH. Six cases with N-myc
      amplification by Southern and/or FISH had diploid tumors and two cases without
      amplified N-myc showed aneuploidy. The remaining one case consisted of
      heterogeneous elements showing diploidy in undifferentiated tissue and both
      aneuploidy (ganglionic cells) and diploidy (Schwann cells) in differentiated
      area. We conclude that FISH is a practical, useful and reliable method over
      Southern especially for analysis of N-myc amplification in neuroblastoma, and
      simultaneous cohybridization with a specific chromosome probe is of great value
      in predicting the prognosis of patients.

PMID- 9180917
TI  - Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis.
AB  - Pneumothorax is an unusual complication of pulmonary Langerhans cell
      histiocytosis. We report three children who developed recurrent intrathoracic air
      leaks. In one case, bilateral pneumothoraces may have been precipated by
      intermittent positive pressure ventilation during general anaesthesia. Chemical
      pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two
      children. The use of extracorporeal membrane oxygenation as an alternative to
      intermittent positive pressure ventilation in children with respiratory failure
      from Langerhans cell histiocytosis is discussed.

PMID- 9180918
TI  - Cavernous transformation of the portal vein in a child with non-Hodgkin's
      lymphoma.
AB  - We present an 11 year old boy who developed collateral vessels in the portal
      hepatis with non-visualization of the portal vein 9 months after treatment for
      large cell lymphoma. This "cavernous transformation of the portal vein" may lead
      to varices with subsequent gastrointestinal hemorrhage.

PMID- 9180919
TI  - Transformation of chronic lymphocytic leukemia to immunoblastic lymphoma
      (Richter's syndrome)

PMID- 9180920
TI  - Multiple central nervous system hemangioblastomas.

PMID- 9180921
TI  - Errors involving pediatric patients receiving chemotherapy: a literature review.

PMID- 9180922
TI  - Eleventh Aspen Cancer Conference: mechanisms of toxicity and carcinogenesis.

PMID- 9180924
TI  - Loss of heterozygosity at loci on chromosome 4, a common genetic event during the
      spontaneous immortalization of mouse embryonic fibroblasts.
AB  - Spontaneously immortalized fibroblast cell lines derived from embryonic tissues
      of C3D2F1, mice were analyzed for loss of heterozygosity (LOH) at multiple
      chromosomal loci to identify candidate suppressor loci for immortalization. Among
      47 simple sequence repeat (SSR) loci selected for screening, those on chromosome
      4 exhibited an exceptionally high LDH incidence of up to 89%. Only four other
      chromosomes (8, 11, 12, and 18) showed LOH, with the highest incidence being 33%.
      To further localize candidate suppressor genes on mouse chromosome 4, detailed
      deletion mapping was performed with 18 cell lines and 14 SSR markers. The
      greatest LOH incidence (94%) was observed at the D4Mit14 locus located on distal
      chromosome 4, indicating that a major suppressor gene resides in this region. On
      the other hand, at the D4Mit77 locus, 30 cM proximal to the D4Mit14 locus, we
      found the SSR to be homozygously lost in 39% of the cell lines. Because the
      D4Mit77 is tightly linked to the tumor suppressor gene p16, for which homozygous
      deletion has been reported in various human tumor cell lines, we also examined
      our fibroblast cell lines for gross aberrations of the p16 gene by using the
      Southern blot method. The p16 gene was found to be homozygously deleted in 56% of
      the cell lines. Although this result implies that the p16 gene plays a role as a
      suppressor gene for immortalization, the combined incidence of LOH and homozygous
      deletion at the D4Mit77 locus was 72%, which is significantly lower than the
      observed incidence at the D4Mit14 locus. Consequently, we concluded that
      immortalization of mouse embryonic fibroblasts may involve more than one
      suppressor gene on chromosome 4.

PMID- 9180923
TI  - Consistent allelic loss on mouse chromosome 7 distal to tyrosinase in 4
      nitroquinoline-1-oxide-induced oral cavity tumors with loss of heterozygosity at
      Ha-ras-1.
AB  - We have previously shown that all CBA/J mice exposed to 4-nitroquinoline-1-oxide
      (4NQO) eventually develop oral cavity squamous cell carcinomas, and two-thirds of
      these tumors have Ha-ras-1 (Hras1) point mutations at codon 12. Half of the
      tumors with Hras1 mutations have loss of heterozygosity (LOH) at Hras1. In the
      study reported here, seven tumors with LOH at Hras1, six heterozygous for Hras1,
      and six without Hras1 mutations were analyzed to define the extent of LOH on
      chromosome (Chr) 7. Microsatellite polymorphisms present in CBA/J mice were used
      as informative allelic markers. Tumors with LOH at Hras1 showed consistent
      allelic loss at the distal portion of Chr 7. The boundary of allelic loss lay
      between the tyrosinase and hemoglobin beta chain loci, which are 6 cM apart. None
      of the tumors that remained heterozygous for Hras1 or had no Hras1 mutations had
      evidence of chromosomal loss involving Chr 7. Because LOH was only detected in
      advanced lesions long after exposure to 4NQO had ceased, we presume that the
      chromosomal alterations by which LOH occurred were independent of the carcinogen
      exposure. The development of LOH in only half of the tumors with Hras1 point
      mutations suggests that LOH was not caused by the initial Hras1 point mutation
      but was a highly selected event during tumorigenesis.

PMID- 9180925
TI  - Expression of bcl-2, bax, and bcl-XL proteins in azoxymethane-induced rat colonic
      adenocarcinomas.
AB  - Using western blotting and immunochemical analysis, we investigated alterations
      in the expression of the apoptosis-related proteins bcl-2, bax, and bcl-X in
      colonic adenocarcinomas induced by subcutaneous injection of azoxymethane (AOM)
      (15 mg/kg body weight weekly for 2 wk) into male Sprague-Dawley rats. Expression
      of the apoptosis-repressor bcl-2 in the colonic tumors was significantly weaker
      (0.6-fold) than that in adjacent non-neoplastic mucosa. The expression of bax
      protein, an apoptosis accelerator, was significantly stronger (7.33-fold) in all
      the tumors than in the non-tumoral mucosa. bcl-XL protein, which functions as a
      repressor of apoptosis, was significantly upregulated (3.23-fold) in all the
      tumors when compared with the non-neoplastic mucosa. There was no significant
      difference between the expression of these proteins in the non-neoplastic mucosa
      of the AOM-treated rats and in the normal mucosa of saline-treated control rats.
      As determined by immunohistochemical analysis, the tumor cells had more bax and
      bcl-X protein. These findings indicate that the regulation of the apoptosis
      related proteins bcl-2, bax, and bcl-XL was altered in the AOM-induced colonic
      neoplastic tissue. In terms of resistance to apoptosis, elevated levels bcl-XL
      protein may have considerable meaning in this experimental model as well as in
      human colorectal cancer.

PMID- 9180926
TI  - Altered gene expression in spontaneous hepatocellular carcinomas from male B6C3F1
      mice.
AB  - In this study, we analyzed spontaneous hepatocellular carcinomas (HCCs) from male
      B6C3F1 mice for alterations in the expression of the genes for c-myc, insulin
      like growth factor II (IGF-II), cyclin D1, transforming growth factor-alpha (TGF
      alpha), and the epidermal growth factor receptor (EGFR). These genes are all
      important in growth control in the rodent liver, and therefore, alterations in
      these genes or their products may result in unregulated growth. Northern blot
      analysis demonstrated an increase in expression of c-myc mRNA in five of 21 (24%)
      spontaneous HCCs compared with nontumor tissue. Tumors that had an increase in c
      myc mRNA did not have an amplified c-myc gene. Of the HCCs analyzed, 18 of 29
      (62%) showed reexpression of IGF-II RNA when compared with controls. Cyclin D1
      mRNA was overexpressed in seven of 27 (26%) of the tumors analyzed relative to
      controls. Tumors with an increase in cyclin D1 mRNA also overexpressed the cyclin
      D1 protein. RNA encoding for the EGFR was decreased in 21 of 23 (91%) HCCs when
      compared with controls. None of the 29 liver tumors analyzed for alterations in
      expression of TGF-alpha mRNA differed from controls. Also, each individual tumor
      had a unique set of molecular alterations even when different tumors from the
      same animal were analyzed. These novel findings suggest that IGF-II, cyclin D1. c
      myc, and EGFR are important mediators of carcinogenesis in spontaneous mouse
      liver tumor formation.

PMID- 9180927
TI  - Mutation spectra analysis suggests that N-(2-chloroethyl)-N'-cyclohexyl-N
      nitrosourea-induced lesions are subject to transcription-coupled repair in
      Escherichia coli.
AB  - To determine the influence of some bacterial DNA repair pathways on the mutagenic
      and the lethal effects of N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea (CCNU),
      pZ189 plasmids treated in vitro with 2 mM CCNU were transfected into Escherichia
      coli strains with different repair capacities (uvr+ada+ogt+, uvr-ada+ogt+, and
      uvr-ada-ogt-). Despite the differences in repair capacities, no statistically
      significant difference in survival and mutability was observed among the tested
      strains. One hundred and sixty-six CCNU-induced supF mutants were isolated and
      sequenced. All mutants were characterized by single base-pair substitutions, most
      of which (more than 96%) were GC-->AT transitions (the mutated G being almost
      exclusively preceded 5' by a purine). Mutation distribution was not random.
      Position 160 (5'-GGT-3', nontranscribed (NT) strand) was a uvr+ada+ogt(+)
      specific hot-spot. Position 123 (5'-GGG-3', NT strand) was a common hot-spot but
      significantly more mutable in repair-proficient strains than in repair-deficient
      strains. Conversely, position 168 (5'-GGA-3', transcribed (T) strand) was
      significantly more mutable in repair-deficient strains than in repair-proficient
      strains. By applying a computer program for comparison of mutational spectra, we
      found that the uvr+ mutational spectrum was significantly different from those
      obtained in uvr- strains, whereas in the uvr- background, no difference was
      observed between mutation spectra in ada+ogt+ versus ada-ogt- strains. Our
      results are consistent with the hypothesis that O6-alkylguanine is responsible
      for most mutations observed in all strains. The results also indicate that
      excision repair modulates the distribution of GC-->AT transitions. The fact that
      mutations at G lesions on the T strand were significantly less frequent in uvr+
      than in uvr- strains suggests that CCNU-induced premutational lesions are
      susceptible to strand-preferential repair in E. coli.

PMID- 9180928
TI  - Spontaneous liver tumors and benzo[a]pyrene-induced lymphomas in XPA-deficient
      mice.
AB  - Defects in the xeroderma pigmentosum complementation group A-correcting (XPA)
      gene, which encodes a component of the nucleotide excision repair (NER) pathway,
      are associated with the cancer-prone human disease xeroderma pigmentosum. We
      previously generated mice lacking the XPA gene, which develop normally but are
      highly sensitive to ultraviolet-B and 7,12-dimethylbenz[a] anthracene-induced
      skin tumors. Here we report that XPA-deficient mice spontaneously developed
      hepatocellular adenomas at a low frequency as they aged. Furthermore, oral
      treatment of XPA-deficient mice with the carcinogen benzo[a]pyrene (B[a]P)
      resulted in the induction of mainly lymphomas. These tumors appeared earlier and
      with a higher incidence than in B[a]P-treated wild-type and heterozygous mice.
      Our results show for the first time that XPA-deficient mice also displayed an
      increased sensitivity to developing tumors other than tumors of the skin.

PMID- 9180929
TI  - Metastatic ability of MXT mouse mammary subpopulations correlates with clonal
      expression and/or membrane-association of gelatinase A.
AB  - We have developed a novel murine mammary tumor system with variants representing
      different stages of tumor progression. The MXT-s parental cell line was
      established from a urethane-induced and hormone-sensitive mammary tumor. MXT-s
      parental cells are highly tumorigenic but poorly metastatic. MXT clones and
      variants were selected by either in vitro or in vivo procedures, and they differ
      in metastatic ability and 17 beta-estradiol dependency for tumor growth. The MXT
      c1.1 and MXT-B2 cell lines produced lung metastasis after intravenous injection
      into 100% of syngenic mice, but only MXT-c1.1 cells were highly metastatic from
      intramammary tumors. The fingerprints obtained by arbitrarily primed-polymerase
      chain reaction demonstrated that the metastatic variants and clones had a common
      genetic background and resulted from clonal selection from the parental cell
      line. We studied whether the matrix metalloproteinase (MMP) profile is correlated
      with tumor progression and metastatic ability in the MXT tumor system.
      Gelatinases A and B were assayed in the cells, both by enzyme activity and mRNA
      expression. Gelatinase A was expressed in MXT-c1.1 cells, whereas MXT-B2 cells
      did not express either MMP. In contrast, the mammary fat pad tumors expressed
      both gelatinases. Membrane Type 1-MMP transcripts were also detected in MXT cells
      and tumors. Because the mRNA levels of gelatinase. A were low in MXT-B2 tumors,
      we suggested that exogenous gelatinase A bound the cell membranes of MXT-B2 cells
      in vivo. Indirect evidence was obtained in vitro by treatment of MXT-B2 cells
      with NIH/3T3 fibroblast-conditioned medium. After this treatment, we detected a
      gelatinolytic activity at M(r) 68,000 in the cell-membrane extract of MXT-B2
      cells and an increase in migratory ability through type IV collagen matrices. On
      the other hand, Ha-ras gene dosage correlated positively with metastatic ability
      but not with either gelatinase A or gelatinase B expression. No significant
      differences were observed in the expression of stromelysin-1 and tissue
      inhibitors of MMP. Thus, in the MXT tumor system, the expression of gelatinase A
      or its cell association and Ha-ras gene dosage independently contribute to the
      metastatic phenotype.

PMID- 9180930
TI  - Abnormal p53 expression is rare in clinically localized human prostate cancer:
      comparison between immunohistochemical and molecular detection of p53 mutations.
AB  - BACKGROUND: We assessed the frequency and molecular basis of p53 mutations in
      clinically localized prostatic adenocarcinoma. METHODS: Prostate specimens were
      examined from 100 patients with clinically localized prostatic adenocarcinoma and
      13 patients with benign prostatic hyperplasia (BPH). Mutations producing nuclear
      accumulation of p53 were detected immunohistochemically. Exon-specific mutations
      were analyzed by polymerase chain reaction amplification and single strand
      conformation polymorphism (PCR-SSCP) and sequenced. RESULTS: p53 accumulation was
      detected in 5 tumors using antibody DO-1, and in 4 of these using antibody PAb
      1801, but not in BPH. PCR-SSCP detected mutations in all 5 tumors, with
      alterations in exon 5 for 1 tumor, exon 6 for 3 tumors, and exon 7 for 1 tumor.
      An exon 6 mutation was also found in a tumor with no anti-p53 staining.
      CONCLUSIONS: p53 mutations are uncommon in clinically localized prostatic
      adenocarcinoma and absent from BPH. 5 of the 6 mutations were derived from
      locally invasive, prostate carcinomas, supporting the hypothesis that mutation of
      p53 is a late event in prostate carcinoma progression.

PMID- 9180931
TI  - Alpha-1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy
      tissue according to the affinities for prazosin.
AB  - BACKGROUND: A novel classification of alpha-1 adrenoceptor subtypes (High, Low)
      was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS: Human
      BPH specimens were examined by a radioligand binding assay method using 3H
      prazosin, and those data were compared with preoperative therapies. RESULTS: (1)
      Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29
      +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd:
      4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype,
      for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n =
      5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either
      alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had
      different pKi values for the above two adrenoceptor subtypes. Scatchard analysis
      showed that alpha 1-high affinity binding site disappeared in the presence of 1
      microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1
      microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site
      of the two subtypes. CONCLUSIONS: Human BPH tissue possesses both alpha 1H- and
      alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only
      the alpha 1H subtype can be completely inhibited by some concentration of
      phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of
      alpha 1-adrenoceptors in prostatic tissue.

PMID- 9180932
TI  - Basic fibroblast growth factor levels in cancer cells and in sera of patients
      suffering from proliferative disorders of the prostate.
AB  - BACKGROUND: Both benign and malignant growth of the prostate depend on the
      induction of a microvasculature. Basic fibroblast growth factor (bFGF), a potent
      angiogenic factor, is thought to play an important role in this process. METHODS:
      bFGF expression in prostatic carcinoma was assessed by ELISA, reverse
      transcription polymerase chain reaction, and immunohistochemistry. RESULTS: DU
      145 and PC-3 tumor cells produced bFGF. Almost 80-90% of it was localized in the
      cytoplasm, and 10-20% was associated with extracellular matrix components.
      Immunohistochemical analysis of prostatic tissue sections showed that cancer
      cells stained more intensively as compared to putatively healthy epithelium. In
      prostate cancer patients, mean bFGF serum levels were significantly elevated when
      compared to a healthy control group (6.64 pg/ml vs. 1.28 pg/ml). Serum bFGF
      levels did not correlate with any other clinical marker such as PSA, tumor stage,
      or grade. Four out of five patients who progressed to a more advanced stage
      showed an increase in serum bFGF levels. CONCLUSIONS: These results suggest that
      increased bFGF release may be associated with a more aggressive tumor phenotype.

PMID- 9180933
TI  - Morphological analogies of fetal prostate stroma and stromal nodules in BPH.
AB  - BACKGROUND: A "reawakening" of ontogenetic processes in the development of BPH is
      still in debate. Therefore, morphological analogies of fetal prostate stroma and
      nodular stromal proliferates in BPH were investigated. METHODS: Fetal prostates
      (n = 30; weeks 12-40 of gestation) and stromal nodules of benign prostatic
      hyperplasia (n = 375 from autopsies, n = 100 from biopsies) were investigated by
      histo- and immunohistochemistry with special regard to cytoskeletal (alpha-actin,
      desmin, myosin, and vimentin), neuronal (S-100 protein), neuroendocrine (neuron
      specific enolase), leukocytic (CD3, CD20, and CD68) and vascular (CD34, BMA-120,
      and factor VIII) antigens. RESULTS: The developing fetal prostate stroma consists
      of immature mesenchymal cells up to week 17 of gestation, followed by
      fibroblastic and fibromuscular stromal cells up to week 25 of gestation and
      predominantly smooth-muscular cells until the end of gestation. Stromal nodules
      occur as immature mesenchymal, fibroblastic, fibromuscular, and smooth-muscular,
      suggestive of a maturational process. The fetal prostate stroma and the stromal
      nodules present, with an increasing degree of maturation, a similar vascular
      pattern and a similar occurrence of CD3 (T-lymphocytes), CD20 (B-lymphocytes),
      CD68 (macrophages), S-100, and neuron-specific enolase-positive cells.
      CONCLUSIONS: The data suggest that ontogenetic processes are recapitulated in the
      development of stromal nodules in benign prostatic hyperplasia, supporting the
      idea of a "re-awakening" of fetal processes in BPH.

PMID- 9180935
TI  - Comparison of androgen-independent growth and androgen-dependent growth in BPH
      and cancer tissue from the same radical prostatectomies in sponge-gel matrix
      histoculture.
AB  - BACKGROUND: In order to determine androgen sensitivities of prostate cancer and
      benign prostatic hypertrophy (BPH) tissues from the same patient in vitro, we
      used a histoculture technique to measure androgen-independent and androgen
      dependent growth and compared them in paired specimens of BPH and prostate cancer
      from 23 radical prostatectomies. Both androgen-independent growth and androgen
      dependent growth are measures of important biological characteristics of benign
      and malignant prostate tissue. METHODS: The effect of hydroxyflutamide and
      antiandrogens on dihydrotestosterone (DHT)-stimulated incorporation of 3H
      thymidine into both paired specimens of BPH and cancer was utilized to measure
      androgen-independent and androgen-dependent growth. The percentage decrease in 3H
      thymidine incorporation/microgram protein in the flutamide-treated specimen
      compared to the DHT-treated specimen represented androgen-dependent growth.
      Residual 3H-thymidine incorporation/microgram protein during hydroxyflutamide
      administration represented androgen-independent growth. RESULTS: Androgen
      independent growth was significantly greater (P = 0.015) in the BPH compared to
      the cancer paired tissue. Androgen-dependent growth was significantly higher in
      23 paired specimens of cancer compared to BPH (P < 0.03). CONCLUSIONS: In paired
      specimens of BPH and prostate cancer from the same radical prostatectomy
      specimen, androgen-independent growth appeared greater in BPH compared to cancer
      specimens; androgen-dependent growth, however, was greater in prostate cancer
      than in BPH. There was no correlation of either growth parameter with Gleason
      tumor grade. Future clinical correlations will indicate whether either growth
      parameter represents an important prognostic factor for prostate cancer
      aggressiveness stimulated 3H-thymidine incorporation into DNA.

PMID- 9180934
TI  - FR146687, a novel steroid 5 alpha-reductase inhibitor: in vitro and in vivo
      effects on prostates.
AB  - BACKGROUND: Steroid 5 alpha-reductase is implicated in the pathogenesis of benign
      prostatic hyperplasia (BPH). We studied the in vitro and in vivo effects of
      FR146687, a new inhibitor of 5 alpha-reductase. METHODS: Two isozymes of rat and
      human 5 alpha-reductases were expressed in 293 cells. In vivo effects of drugs
      were evaluated on rat and dog prostates. Castrated immature rats were injected
      with testosterone propionate (TP) or 5 alpha-dihydrotestosterone propionate
      (DHTP) to induce growth of the ventral prostates. Testosterone and 5 alpha
      dihydrotestosterone (DHT) contents in rat and dog prostates were measured by gas
      chromatography-mass spectrophotometry (GC-MS). RESULTS: FR146687 showed
      noncompetitive inhibition in both isozymes and no inhibitory effects on other
      steroid oxidoreductases. In mature rats and castrated immature rats treated with
      TP, FR146687 dose-dependently reduced ventral prostate and seminal vesicle weight
      at doses above 0.1 mg/kg, while castrated immature rats treated with DHTP were
      not affected by FR146687. FR146687 showed more potent reduction of rat prostates
      than finasteride. DHT concentration in the prostates was significantly reduced
      when FR146687 was administered to rats and beagles. CONCLUSIONS: FR146687 is a
      dual inhibitor for 5 alpha-reductase isozymes and significantly reduced the
      growth and DHT content in the prostate.

PMID- 9180936
TI  - Are contact laser, interstitial laser, and transurethral ultrasound-guided laser
      induced prostatectomy superior to transurethral prostatectomy?
AB  - BACKGROUND: In order to assess the value of various new therapeutic modalities in
      the management of benign prostatic hyperplasia (BPH), we performed a prospective
      study comparing transurethral resection of the prostate (TURP) to contact Laser,
      interstitial Laser, and transurethral ultrasound-guided laser-induced
      prostatectomy (TULIP). METHODS: The following parameters were evaluated
      preoperatively as well as 3, 6, and 12 months after surgery: prostatic volume,
      urinary flow rate, postvoid residual volume, and the AUA symptom score. The
      diagnosis of bladder outlet obstruction was established preoperatively by means
      of pressure/flow studies which were repeated 1 year after the operation. RESULTS
      AND CONCLUSIONS: In conclusion, TURP is still the gold standard in the treatment
      of BPH. The results of TULIP, contact laser, and interstitial laser are about the
      same. The time intervals within which the patients become free of symptoms,
      however, vary widely. Contact laser is limited to prostates below 50 cc, while
      interstitial laser is ideal for patients in poor general health who present with
      large prostates. Furthermore, our results demonstrate that the only reliable data
      for determining the degree of posttherapeutic disobstruction can be provided by
      urodynamic investigations including pressure/flow diagrams.

PMID- 9180937
TI  - Diagnostic and prognostic markers for human prostate cancer.
AB  - BACKGROUND: The incidence and mortality of prostate cancer are increasing at
      alarming rates, partially due to an aging population. Early detection of prostate
      cancer, using clinically sensitive procedures and/or tumor markers (e.g.,
      prostate-specific antigen [PSA]), is of prime importance. However, the choice of
      therapeutic interventions for prostate cancer at the time of diagnosis is largely
      dependent on clinical and pathologic staging and prediction of the degree of
      aggressiveness of the disease. Clinically applicable prognostic markers are
      urgently needed to assist in the selection of optimal therapy. METHODS:
      Literature review of the potential diagnostic and prognostic markers for human
      prostate cancer. RESULTS: Well-established tissue prognostic indicators,
      including histologic grade, margin positivity, pathologic stage, intraglandular
      tumor extent, and DNA ploidy, are not reviewed in this paper. Recently, a number
      of novel markers have been identified. In this paper, we begin with a discussion
      of a number of well-established as well as investigational diagnostic markers and
      then focus on evaluation of prognostic markers. Diagnostic markers that have
      prognostic value and investigational prognostic markers are also discussed.
      CONCLUSIONS: Currently, only PSA is utilized for early diagnosis and monitoring
      of prostate cancer. A number of potential prognostic markers warrant further
      investigation. Multimarker analysis is implicated.

PMID- 9180938
TI  - GAPO syndrome (Radiographic clues to early diagnosis).

PMID- 9180939
TI  - 1997 Annual Scientific Meeting of the Research Society on Alcoholism. San
      Francisco, California, July 19-24, 1997. Abstracts.

PMID- 9180940
TI  - 10th World Congress on In Vitro Fertilization and Assisted Reproduction.
      Vancouver, British Columbia, Canada, May 24-28, 1997. Abstracts.

PMID- 9180942
TI  - 81st Meeting of the German Society of Pathology. Berlin, Germany, 21-24 May 1997.
      Abstracts.

PMID- 9180941
TI  - 5th International Congress of Vertebrate Morphology. Bristol, United Kingdom,
      July 12-17, 1997 Abstracts.

PMID- 9180944
TI  - XXVIII National Congress of the Italian Pharmacological Society. Bari, Italy,
      April 30-May 3, 1997. Abstracts.

PMID- 9180945
TI  - 1997 Annual Meeting and 37th Symposia of the Japanese Society of Plant
      Physiologists. March 27-29, 1997. Abstracts.

PMID- 9180943
TI  - Deutsche Physiologische Gesellschaft. Abstracts of the 76th Annual Meeting. 11-15
      March 1997, Rostock.

PMID- 9180946
TI  - International joint meeting of physiology. XXVIII National Congress of the
      Spanish Society of Physiological Sciences and the American Physiological Society.
      Malaga, Costa del Sol, Spain, 4-7 February 1997. Abstracts.

PMID- 9180947
TI  - Gastric ulcer and cancer ulcer. Retrospective evaluation of the current
      endoscopic diagnosis.
AB  - Aim of this experience has been to evaluate the current diagnostic potentiality
      of the endoscopy in the framework of the gastric ulcerous pathology. On the total
      of the gastric ulcers 17.9% have resulted to be neoplastic with the hystologic
      examination. The diagnostic accurracy of the endoscopy has resulted to be of the
      87% compared to hystology. From our data it is evidenced how the endoscopy
      examination has a relevant diagnostic accuracy in defining the nature of the
      gastric ulcer which however has to be confirmed by the histology which seems to
      be diriment.

PMID- 9180948
TI  - [Comparison between gastric and esophageal mechano-sensitivity in patients with
      functional dyspepsia].
AB  - Patients with non ulcer dyspepsia (NUD) and lowered mechano sensitivity
      thresholds in stomach may have lowered mechano sensitivity thresholds in
      oesophagus also. The aim was to check this hypothesis. METHODS: 39 patients with
      NUD (11 men and 24 women, mean age 57 years, SEM 3.72, range 17-86) and 20
      controls (10 men, 10 women, mean age 49.3 years, SEM 3.72, range 31-66) were
      studied. Organis diseases were discarded. Gastric mechano sensitivity was studied
      with a latex balloon of low compliance, 8 cm length, connected to a manometer.
      Balloon was inflated "in ramp" at 10 ml/sec, and "first sensation", discomfort",
      and "pain" were registered. At 900 ml inflation was stopped if pain was not
      evoked. Oesophageal mechano sensitivity was studied with another latex balloon of
      low compliance which, after inflated with 15 ml. of air, was 3.5 cm. in diameter.
      Esophageal balloon was inflated "in ramp" (1 ml/sec) up 15 ml. and deflated in 2
      cm step from 36 to 22 cm from SDA. Inflation was stopped when symptoms (pain or
      discomfort were evoked. Oesophageal acid perfusion test was performed. RESULTS:
      83.4% of controls completed up 700 ml. of gastric distension vs. 35.9% of
      patients with NUD (p > 0.001). No significative differences in intra-balloon
      pressure slope were observed between both groups. 79.2% of NUD patients had chest
      pain with oesophageal ballon distension = < 7 ml. vs. 5% in controls (p > 0.001).
      Mean volumes were 7.03 ml. (NUD) and 11.9% (controls) (p = 0.001), 63% of
      dyspeptic patients with lowered gastric sensitivity thresholds (< 700 ml) had
      oesophagic symptoms with inflation volumes = < 7 ml. There was a positive
      correlation in stomach and oesophageal mechano sensitivities variations (r =
      0.75, +/- 0.58, p > 0.01). When analyzed with that results, oesophageal acid
      perfusion test showed 38.5% of "mixed sensitivities" (both mechano- and chemo-),
      30.7% of "mechano sensorials" (negative acid test, positive balloon test), and
      10.3% of :chemo sensorials" (positive acid test only). In 20.5% both tests were
      normal at the moment they were done. These results agreed with our previous
      experiences in oesophagus. CONCLUSIONS: It was concluded that a significative
      proportion of NUD patients had lowered thresholds for mechano stimulation of
      stomach and oesophagus at the time that both tests were done. Such alterations
      support the hypothesis that a more general mechano-sensitivity alteration is
      present in patients with NUD.

PMID- 9180949
TI  - [Interferon alfa in the treatment of chronic hepatitis C: course of 24 versus 48
      weeks. Results of a randomized trial].
AB  - The aim of this trial was to investigate if a more prolonged course of interferon
      (IFN) is able to increase the long-term benefit in patients with chronic
      hepatitis C. Forty-four patients with active chronic hepatitis and antibodies to
      HCV were randomly assigned to receive IFN-alfa 2b 3 MU t.i.w. during 24 weeks
      (group I, n 23) or during 48 weeks (group II, n 21). In the evaluation of
      results, complete response was considered when the ALT values returned to
      normality during the treatment; and sustained response, when the ALT values
      persisted below normal range during at least 6 months post therapy. Histologic
      changes were compared by using the Histological Activity Index, or Knodell score.
      Viremia status was evaluated for the study of HCV RNA (by nested-RT-PCR).
      RESULTS: There were no significant differences between both groups before
      treatment, in terms of age, sex, ALT, or histologic findings (11 patients in
      group I, and 7 in group II had cirrhosis). Complete response was found in 9
      patients (39.1%) from group I; in 11 (52.4%) from group II (NS). Basal histologic
      findings were identified as the only predictive factor of complete and sustained
      response, by logistic regression analysis. Considering only noncirrhotic
      patients, complete response was seen in 58.3% in patients from group I, 71.4% in
      group II. Sustained response was obtained in 4 patients from group I, (17.4%), 7
      from group II (33.3%) (NS). Post IFN liver biopsies were performed in 23 patients
      (12 from group I, 11 from group II). In group I patients, there were no
      significant changes. In group II, Knodell score was found to be significantly
      decreased post IFN [pre IFN, median 10, range 3-15; post IFN, median 6, range 2
      14] (p < 0.05). HCV RNA was absent in serum during the follow-up post IFN in 2
      patients from group I, in 3 from group II. The results of this study show that a
      48 weeks course of IFN has a trend to achieve a higher sustained response than
      the usual regime (but non significant); and it produces a decrease in the
      histologic activity. The best predictive factor of positive response was the
      absence of cirrhosis in our study (although we did not evaluate viral factors,
      such as genotypes or HCV viremia levels).

PMID- 9180950
TI  - [Botulinum toxin is effective in the short-term treatment of esophageal
      achalasia. Preliminary results of a randomized trial].
AB  - Botulinum toxin (BoTox) is a potent inhibitor of the release of acetylcholine
      from terminal nerves and has been used successfully in spastic disorders of
      skeletal muscle. Its used for the treatment of disorders of gastrointestinal
      smooth muscle has recently been explored. In this study we evaluated the efficacy
      of transendoscopic injection of BoTox in 13 symptomatic patients with achalasia G
      II (Siewert classification) without previous treatment of an ongoing randomized
      controlled trial. Patients were blindly randomized to administrate: a) 8OU of
      BoTox were injected in four quadrants (1 ml in each quadrant-20 U/ml) (n = 8), b)
      normal saline solution as placebo injected in the same way (n = 5). Patients who
      did not respond were retreated in an open design with the same schedule of BoTox.
      BoTox or placebo were injected directly into the lower esophageal sphincter
      (LES), located by manometric and endoscopic procedures, via sclerotherapy
      injector. Response to treatment was assessed by changes in symptoms score,
      weight, LES pressure, barium esophagograms and endoscopy. All determinations were
      repeated at basal and after 7-30-60 and 90 days of treatment. Post treatment
      response was considered positive if at one month, 3 of 4 parameters were
      improved. No evidence of response to BoTox were assessed in 3 patients. At 90
      days, 10 patients remain well and data are as follows: (mean +/- SD) symptoms
      score: (Pre: 3.23 +/- 0.44) (Post: 1.31 +/- 0.95); LES pressure (mmHg) (Pre: 53,
      15 +/- 66.31 +/- 7.49); % reduction of esophageal diameter 55% (p < 0.0001) (pair
      T-test). Relaxation of LES did not change after treatment. There were no side
      effects related to BoTox injection. CONCLUSIONS: Endoscopic intrasphincteric
      BoTox injection is safe, simple and effective in the short term treatment for
      achalasia. Further studies are necessary for evaluation of long term effects.

PMID- 9180951
TI  - Colon epithelial electrical responses to acute hypoxia and reoxygenation in
      vitro.
AB  - Electrogenic epithelial transport depends on oxidative metabolism. Acute hypoxia
      and subsequent reoxygenation effects on short-circuit current (Isc),
      transepithelial potential difference (PD) and tissue resistivity (TR) of rat
      distal colon were assessed. The tissue was mounted in an Ussing chamber filled
      with Ringer-HCO3-solution at 37 degrees C and bubbled with 95% O2- 5% CO2 which
      was switched to 95% N2- 5% CO2 for inducing hypoxia; afterwards normal
      oxygenation was resumed. The effect of 5, 10, 15 and 20 min-hypoxic periods was
      assessed in isolated mucosa preparations. Recovery was complete after 10- and 15
      min hypoxia, but not after 20-min hypoxia. After 5-min hypoxia, an overshoot of
      Isc and PD was seen on reoxygenation. This effect was further characterized
      comparatively in mucosa-submucosa and isolated mucosa preparations. In the former
      (n = 10), control values were Isc = 71.7 +/- 8.6 microA. cm-2, PD = 9.7 +/- 1.6
      mV and TR = 134.9 +/- 13.6 omega cm2. A 5-min hypoxia reduced Isc by 47.2 +/-
      7.3% and PD by 61.5 +/- 4.9%. Peak values on reoxygenation were 28.1 +/- 4.1% for
      Isc and 16.8 +/- 5.4% for PD, over controls values. In the isolated mucosa (n =
      9), control values were Isc = 52.04 +/- 5.5 microA. cm-2, PD = 5.0 +/- 0.8 mV and
      TR = 101.04 +/- 10.5 omega. cm2. In hypoxia, Isc decreased by 64.5 +/- 7.6% and
      PD by 57.2 +/- 7.8%. On reoxygenation peak values of 78.0 +/- 19.0% and 87.5 +/-
      17.1%, respectively, were seen. The response to a 5 min-hypoxia was comparable,
      but that to reoxygenation was weaker and slower, in mucosa-submucosa than in
      isolated mucosa preparations. This may be explained by a hindrance to oxygen
      diffusion caused by the submucosal tissue. TR did not change with any period of
      hypoxia tested, but decreased slightly (8.9 +/- 1.3%) upon reoxygenation in the
      mucosa-submucosa preparations. Ouabain (10(-3) M) markedly blunted the response
      to reoxygenation. We conclude that hypoxic periods of 20 min lead to irreversible
      functional deterioration. Hypoxia decreases electrogenic transepithelial pumping,
      which may allow sodium to accumulate intracellularly and, if the hypoxia is short
      enough to prevent damage to the epithelium, increase sodium pump activity when
      oxygenation is resumed.

PMID- 9180952
TI  - Thioctic acid protection against ethanol and indomethacin induced gastric mucosal
      lesions in rats.
AB  - BACKGROUND/AIMS: The gastric protective effect of thioctic acid, a sulfhydryl
      compound, against chemically induced mucosal lesions has not been reported.
      METHODS: Fasted Wistar rats (24 h) were treated (gavage administration) with
      graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by
      the gavage administration of 1 ml 96% ethanol or intraperitoneal administered
      indomethacin. The gastric mucosa was examined grossly and histologically for an
      evaluation of the lesions. RESULTS: Pretreatment of rats with thiotic acid has
      shown a significant decline in the mean number, size, incidence and severity of
      mucosal lesions induced by both ethanol and indomethacin. CONCLUSIONS: This is
      the first evidence that thiotic acid protects the rat gastric mucosa against
      chemically induced damage. Its is speculated that this finding may prove to be
      important in the development of improved therapies for the prevention and
      treatment of gastric ulcers in humans.

PMID- 9180953
TI  - [Effect of microcrystalline cellulose on the excretion of total biliary acids in
      feces].
AB  - The colorectal neoplasia is the second cause of death from neoplasia in our
      country, and in international statistics, blaming for this, the dietetic habits
      of industrialized countries having a high content of satured fat, cholesterol,
      refined carbohydrate, red meat, and with few dietetic fibers. In the last years
      special attention has been focused to the action of the total biliar acids (TBA)
      primarily the secondary ones, over the colon mucosa, showing evidences of
      cancerous effects. Recently, American authors have published the favoring action
      of the cellulose fiber over the TBA through a catalytic reaction and their
      polysterification, inactivating them in their aggressive action over the colon
      mucosa. Through these experiences and willing to prove the action of the product,
      we have treated with microcrystalline cellulosa (Microcel Lab. Blanver, Brasil)
      20 patients of the Institute of Gastroenterology of Havana City, who showed high
      figures of TBA in stools for 2 months, compared with the 5 g. dose per day.
      Another group of 20 patients also with high figures of TBA in stools being
      treated with corn fecula same dose, same time by equal time, making every month
      determinations to both groups, determining that in the first group the figures of
      TBA in stools were normalized in 95% the first month of treatment and in 100% the
      second month. The second group had only an answer of 65% the first month and of
      80% the second month, which shows evidently the high efficacy of Microcel in
      reducing the TBA in stools.

PMID- 9180954
TI  - [Histologic factors as elements of prognostic value in biliary atresia].
AB  - Biliary atresia (BA) is one of the biliary tree anomaly more frequent. Occurs in
      about 0.8 to 1/10.000 live births. BA is defined as a progressive biliary tree.
      The prognosis depends on the age of the diagnosis and precocity surgery. We
      present the results of a retrospective analysis of 71 RA carried out at the
      Garrahan Hospital from 1987 to 1993. 47 were female and 24 were male. Age ranged
      from 45 to 120 days of life. This study involved a consecutive series of 58
      patients with histopathologic study of Porta-hepatis (PH) and liver biopsy
      obtained during the Kasai. The purpose of this study was to determine the value
      of histological factors as type of PH and hepatocytic giant cell transformation
      (GCT). 82.8% had favorable type of PH and the CCT was mild in 84.5%. 72.4% had
      bad outcome and was independent of the type of PH. Neither of them were
      statistically significant with survive and evolution. In our service neither PH
      non CGT were predictors of a bad outcome. There were good outcome in 27.5%, died
      37.9% and 10.3% undergo liver transplantation. The precocity in a diagnosis and
      surgical procedure before two months of age are the most important factors in
      correlation with survival. Others immunomorphologic factors must be studied in BA
      that explained the etiopathogenic process. Orthotopic liver transplantation is
      the successful therapy in children with BA.

PMID- 9180955
TI  - [Gastroesophageal reflux, pulmonary and gastric function in patients with cystic
      fibrosis. Results of a randomized trial].
AB  - We studied ten patients with Cystic fibrosis. The purposes of this study were to
      investigate the presence of gastroesophageal reflux and establish the probable
      association between gastroesophageal reflux and pulmonary and gastric
      involvement. All 10 patients underwent 24-hour esophageal pH recording,
      spirometry and gastric function. Abnormal reflux index was found in all these
      patients. Lung function was pathologic in the 3 older children. There were no
      relationship between the severity of the gastroesophageal reflux and the degree
      of pulmonary damage. No patient has gastric acid hypersecretion. Eight of 10
      patients had steatorrhea. Our findings confirm the high frequence of
      gastroesophageal reflux in cystic fibrosis.

PMID- 9180957
TI  - [Ulcer-cancer or early or advanced ulcerative cancer: an habitual diagnosis
      challenge: contribution of endoscopy and pathology].

PMID- 9180956
TI  - [Suitability of laparoscopic cholecystectomy in the asymptomatic cholelithiasis
      patient].
AB  - Cholelithiasis is a disease of high prevalence in the adult population.
      Prevalence increases with age; the incidence of complications, such as
      choledocholithiasis, acute pancreatitis, and cancer of gallbladder, also increase
      with age. Cholecystectomy has been considered as the gold standard in the
      treatment of symptomatic or complicated cholelithiasis. Laparoscopic
      cholecystectomy has become the new gold standard. Our Department of Surgery has
      adopted a policy of advising laparoscopic cholecystectomy in all patients with
      symptomatic cholelithiasis, but also subpopulation of high risk asymptomatic
      patients. This subgroup is made up by patients with long life expectancy,
      radioopaque stones, small calculus with patent cystic duct, nonfunctioning or
      calcified gall bladder, and patients with concomitant diabetes, cirrhosis,
      chronic hemolytic anemia, those that are candidates for kidney or heart
      transplantation, and those with underling degenerative diseases that are more
      likely to develop severe complication of cholelithiasis. Csendes of Chile has
      reported very high incidence of gallbladder cancer in Chile and Bolivia. He
      considers that cholecystectomy is indicated in asymptomatic patients as a
      "prophylactic" measure. Our group agrees that this is a valid indication in areas
      or populations groups where gallbladder cancer is of high prevalence.

PMID- 9180958
TI  - Hepatic hydatidosis.

PMID- 9180959
TI  - [Why hepatitis and AIDS?].

PMID- 9180960
TI  - [Prescription of laboratory tests in 1997].

PMID- 9180961
TI  - [Molecular biology at the service of the daily medical virology. 2. Applications
      to virological diagnosis].
AB  - Molecular biology techniques are applied for the diagnosis of meningoencephalitis
      due to herpesviruses, enteroviruses or polyomaviruses, for the diagnosis of human
      cytomegalovirus, human parvovirus B19, varicella-zoster virus and rubella virus
      infections occurring during pregnancy, for the diagnosis and the management of
      retrovirus infections (HIV and HTLV) and of hepatitis (HBV and HCV), for
      papillomavirus typing and to detect a link between virus and clinical
      manifestations (cardiomyopathy or insulinodependent diabetes with coxsackievirus
      B: Kaposi's sarcoma with HHV 8) or to investigate an environmental contamination
      with viruses. These new molecular markers which are both qualitative and
      quantitative represent an important advance in the field of viral diagnosis
      research, in the monitoring of viral load during the course of infection, in the
      therapy control of viral disease and in the epidemiology of virus spread.
      Standardization and automatization are obtained using available commercial
      reagents and kits.

PMID- 9180962
TI  - [The HLA system: a clinical help?].
AB  - Chronic diseases are polymorph and influenced by many environmental and genetic
      factors. The HLA system is implicated in the modulation the onset and the
      evolution of chronic diseases. These observations are important to be considered
      for the prediction, prognosis and treatment adaptation. Evaluation tests are
      mainly statistical and are based on epidemiological studies. Thus, results must
      be considered with caution. Two aspects are to be considered: DIAGNOSIS:
      Associations between HLA alleles and chronic diseases are well known but concern
      very few diseases like narcolepsy or rheumatoid arthritis. Insulin dependent
      diabetes mellitus is particular because the prediction is limited to familial
      studies. PROGNOSIS: This point is less documented in clinical applications but is
      of interest particularly in inflammatory bowel diseases or systemic affections.
      This observation can be considered as a compartmental response which is a kind of
      adaptation to stress.

PMID- 9180963
TI  - [Biological diagnosis of hemoglobinopathies by phenotype analysis].
AB  - Haemoglobinopathies are defined by the presence of qualitative and/or
      quantitative globin chains abnormalities. In most cases, laboratory diagnosis
      relies on phenotype analysis. Ethnic group, clinical data, complete blood count
      in absence of recent blood transfusion, iron status, should be taken into account
      for the diagnosis. Electrophoresis using an alkaline pH buffer system is used as
      an initial technique for the detection of haemoglobin variants, showing abnormal
      bands as compared with reference samples. Isoelectric focusing is more resolutive
      and could be preferred for this reason: If the migration pattern differs from
      normal, additional confirmatory tests, as citrate agar electrophoresis (acid pH),
      are required. Relative amounts of variant haemoglobin (Hb A2, F and S...) are
      quantified using chromatographic methods. Other tests, such as solubility tests,
      stability tests, Kleihauer-Betke test, are useful in specific cases. The
      diagnosis relies on clinical and laboratory findings. In the Paris area, the most
      common variant is Hb. S. Taalassemia traits are also very common. Screening of
      SS. S beta D. SO Arab, SD Punjab, SC, or thalassaemia major should be made early
      so that patients found to have one of these varieties should be referred to
      haemoglobinopathy centers.

PMID- 9180964
TI  - [Molecular basis of phenotype heterogeneity in cystic fibrosis].
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible
      for the cystic fibrosis phenotype, was cloned and sequenced in 1989. Since then,
      more than 650 mutations have been reported. The analysis of the entire coding
      sequence of the CFTR gene (27 exons) has been able to characterize more than 90%
      of the mutations in different populations. Moreover, screening of the entire
      coding and flanking sequences of the CFTR gene in males with congenital bilateral
      absence of the vas deferens revealed that 80% of these subjects are at least
      heterozygous for a CF mutation. These results help to improve genetic counselling
      and prenatal diagnosis of cystic fibrosis. Different studies examining the
      relation between phenotype and genotype in CF with respect to AF508 or non delta
      F508 mutations have demonstrated that some "severe" mutations are strongly
      associated with pancreatic insufficiency or complications. It has been also
      showed a relationship between the presumed severity of the mutations and the
      observed phenotype, not only for pancreatic status, but also for the severity of
      the respiratory involvement. However, some studies found that some individuals do
      not fit the outcome of their general group of genotype. These findings reinforce
      the conviction that other factors besides the CFTR mutation are involved in the
      severity and outcome of the disease.

PMID- 9180965
TI  - [Measurement of biological activity of hLH. Multicenter study].
AB  - This report describes the results of a multicentric study of biological methods
      for luteinizing hormone (hLH). The production of testosterone by animal Leydig
      cells is used by five laboratories with different methodologies including rat,
      mouse and pig cells. Dose-response curves of testosterone production, quality
      criteria and results on a physiological population of men and women, are reported
      and discussed. It is concluded that the bioactive determination of hLH must be
      considered as a reference method used in discordances between clinic and
      immunological methods.

PMID- 9180966
TI  - [Role of hygiene and bacteriological laboratories in the management of an
      epidemic of Enterobacter aerogenes multiresistant to antibiotics].
AB  - We describe a multiresistant Enterobacter aerogenes outbreak in an intensive care
      unit. An epidemiology study based on phenotypic characters (species diagnosis and
      antibiotype) was completed by a genotypic study (pulsed field electrophoresis) to
      confirm bacterial clonality. The hygiene laboratory proposed numerous preventive
      measures to limit bacterial dispersion. We describe the role of bacteriologists,
      hygienists and medical staff to stop the bacterial dispersion.

PMID- 9180967
TI  - [Rapid determination by immunoassay of glycosylated hemoglobin in capillary blood
      compared to an affinity method for boronate and ion capturing on venous blood].
AB  - Measurement of glycosylated haemoglobin has become an essential tool in the
      management of diabetic patients. A recently developed device allows the rapid
      immuno-assay of HbA1c in 1 microliter capillary blood obtained by a finger prick.
      In 100 ambulatory diabetic patients, we compared the results obtained with this
      method to those obtained in venous blood using a standard affinity chromatography
      laboratory method. Although both methods correlated (r = 0.88, p < 0.001), the
      mean +/- SD levels respectively obtained differed slightly (7.6 +/- 1.5 vs 79 +/-
      1.4% p < 0.001). The 95% confidence interval of the difference was [-0.41. 
      0.14]. Considering a cut-off HbA1c value of 8%, as indicative of the need for
      treatment adjustment, 33 patients with the capillary blood immuno-assay method
      and 42 with the venous-blood affinity chromatography method were above that limit
      (Mc Nemar test, p < 0.05). In conclusion, the rapid assay of HbA1c in capillary
      blood can be useful for the management of some diabetic patients but the results
      are not readily exchangeable with those obtained from other standardized
      laboratory methods. Consequently, specific ranges and clinical decision limits
      must be determined.

PMID- 9180969
TI  - [Think of varicella pneumopathy in an immunocompromised patient].

PMID- 9180970
TI  - [Apropos of pneumopathy in a cardiac graft patient].

PMID- 9180968
TI  - [Apropos of a case with herpes meningoencephalitis].

PMID- 9180971
TI  - [Apropos of a case with disseminated intravascular coagulation in a pregnant
      woman].

PMID- 9180972
TI  - [Value of a control of external quality of spermato-cytograms and perspectives].

PMID- 9180973
TI  - [150th anniversary of inhalation anesthesia. Le Comite de Redaction des AFAR].

PMID- 9180974
TI  - [Blood loss from diagnostic laboratory tests performed in intensive care units.
      Preliminary study].
AB  - OBJECTIVE: To assess the volume of blood samples withdrawn for laboratory testing
      in intensive care unit (ICU) patients and to determine the influence of the
      resulting blood loss on transfusion requirements in patients staying in the ICU
      for more than seven days. STUDY DESIGN: Prospective clinical open study.
      PATIENTS: Fifty patients treated in the ICU over the 3-month study period,
      neither admitted for a systematic postoperative monitoring, nor experiencing
      bleeding or haemolysis. METHODS: For each patient the following data were
      obtained: duration of ICU stay, volume of the daily withdrawn blood, the
      concentration of haemoglobin (Hb) at the time of ICU admission, ICU discharge and
      before each transfusion, volume of transfused blood. RESULTS: A mean volume of 62
      +/- 29 mL.d-1 of blood was taken. It decreased from 85 +/- 6 mL on admission day,
      to 66 +/- 6 mL after seven days and 60 +/- 8 mL after 14 days. About 27% of the
      withdrawn blood was rejected (initial blood reflowing through cannula and
      connection tube). Twenty-one patients (42%) had a length of stay greater than 7
      days. In this population, a first group (13/21) was given transfusions of packed
      red cells during their hospitalisation and a second group (8/21) was not
      transfused. The mean volume of blood taken per day (67 +/- 21 mL.d-1 vs 55 = 15
      mL.d-1) and the total volume (1.204 +/- 810 mL vs 810 +/- 389 mL) were not
      significantly higher in the transfused group. Conversely, the mean haemoglobin
      concentration on ICU admission (97 +/- 22 g.L-1 vs 136 +/- 26 g.L-1) was
      significantly lower (P = 0.001) in the transfused patients. CONCLUSION: Blood
      losses from blood withdrawal for laboratory tests are important and in agreement
      with the results of other reports. It is generally accepted that iatrogenic blood
      loss of this magnitude can cause anaemia if repeated over a prolonged period.
      Conversely, our data suggest that blood sampling does not contribute
      significantly to anaemia and transfusion requirements in patients with a
      prolonged ICU stay.

PMID- 9180975
TI  - [Changes in intraocular pressure during anesthesia with intratracheal intubation
      or laryngeal mask].
AB  - OBJECTIVE: To compare the effects of the laryngeal mask airway (LMA), and the
      tracheal tube (TT) insertion on intra-ocular pressure (IOP) in eye surgery. STUDY
      DESIGN: Prospective non-randomized study. PATIENTS: Eighty patients scheduled for
      eye surgery under general anaesthesia were allocated into either a LMA group (n =
      37) or a TT group (n = 43). METHODS: After induction of anaesthesia with
      propofol, vecuronium and phenoperidine, either a TT or a LMA were inserted. IOP,
      heart rate (HP) and mean arterial pressure (MAP) were measured before (TO) and
      after induction (T1), after TT or LMA insertion (20 s:T2, 6 min:T3), and before
      extubation (T4). RESULTS: The HR, MAP and IOP increased significantly at T2
      (compared to T1 but not to T0) in the TT group, for a short time, whereas no
      significant changes occurred in the LMA group. CONCLUSION: LMA insertion does not
      elicit significant haemodynamic or IOP changes. Conversely, the TT increases HR,
      MAP and IOP. These changes can be deleterious in case of emergency surgery for
      perforating eye injuries. The LMA can be recommended as an alternative to TT in
      eye surgery, provided security rules are followed, because of the risk of
      displacement of LMA during surgery.

PMID- 9180976
TI  - [Gynecologic laparoscopy with or without curare].
AB  - OBJECTIVE: To assess physiological changes and operating conditions during
      general anaesthesia with or without neuromuscular blockade in patients undergoing
      gynaecologic laparoscopy. STUDY DESIGN: Prospective, randomized, double-blind
      study. PATIENTS: Fifty non-obese patients, mean age 31 years, randomly allocated
      into either a group of 25 with curare (AC) or a group of 25 without curare (SC).
      METHODS: All patients were anaesthetized with propofol (2.5 mg.kg-1), sufentanil
      (0.4 microgram.kg-1) midazolam (2 mg) and N2O-O2. In addition, those of the AC
      group were given atracurium 0.25 mg.kg-1 for intubation, followed by additional
      boluses to maintain twitch height < 10% of the control value. Blood pressure,
      heart rate, peak airway pressure, end-tidal carbon dioxide pressure were recorded
      before and during pneumoperitoneum maintained at a pressure of 15 mmHg. Operating
      conditions were assessed at 10-min intervals, using a four point scale. RESULTS:
      In both groups, blood pressure and heart rate decreased following induction. The
      decrease in blood pressure was more important in the SC group at 5 min and before
      pneumoperitoneum (25 vs 15%); P < 0.05). The time course of PETCO2 and peak
      airway pressures were similar between groups. Operating conditions were not
      influenced by the muscle relaxant. CONCLUSIONS: Neuromuscular blockade influences
      neither most of the clinical haemodynamic and respiratory changes induced by
      pneumoperitoneum for gynaecologic laparoscopy not the operating conditions.

PMID- 9180977
TI  - [Does oral ondansetron reduce the incidence of nausea and vomiting after surgery
      for strabismus in children?].
AB  - OBJECTIVE: To compare the efficacy of oral ondansetron with oral metoclopramide
      for the prevention of postoperative vomiting and nausea in children undergoing
      strabismus surgery. STUDY DESIGN: Prospective, randomized, double-blind trial.
      PATIENTS: Thirty children of physical class 1, age 9 +/- 4 years, scheduled for
      strabismus surgery, were randomized into two groups (ondansetron and
      metoclopramide). METHODS: In the ondansetron group, the children received the
      first oral dose of ondansetron (4 mg) 1 hour before induction of anaesthesia and
      the other doses 8 and 16 hours later. In the metoclopramide group, children
      received metoclopramide (5 mg) in the same conditions. Anaesthesia was induced
      with thiopentone, vecuronium and fentanyl and maintained with halothane and
      N2O/O2. Patients were evaluated by an independent observer for nausea and emesis
      in recovery room (0-2 h) and on the ward. The adverse effects of oral ondansetron
      and metoclopramide were assessed. RESULTS: There were non-significant differences
      between the two groups for incidence of nausea and vomiting (40% and 53% in
      ondansetron group versus 33 and 60% in metoclopramide group, respectively.
      CONCLUSION: Unlike intravenous ondansetron, oral ondansetron is not superior to
      metoclopramide for the prevention of nausea and vomiting caused by strabismus
      surgery in children.

PMID- 9180978
TI  - [Measurement of gastric mucosal pH by tonometry in major abdominal surgery].
AB  - OBJECTIVE: To investigate whether changes in gastric intramucosal pH (pHim) occur
      during major abdominal surgery, and if so, to determine the relationship between
      classic global indices of tissue perfusion such as mean arterial blood pressure
      (MAP), heart rate (HR), central venous pressure (CVP), urine flow (UF) and
      arterial pH (pHa). STUDY DESIGN: Prospective descriptive study. PATIENTS: Seven
      ASA2 patients undergoing major abdominal surgery. METHODS: After induction of
      anaesthesia and endotracheal intubation, a tonometer nasogastric tube was
      positioned in the stomach. Measurements of tonometric PCO2 (PCO2ss), end-tidal
      PCO2 (PETCO2), PaCO2, bicarbonates [bicarb], pHa, MAP, HR, CVP and UF were
      collected at baseline (HO), and one, two, three, and 24 hours (H1, H2, H3, and
      H24) after the beginning of surgery. RESULTS: Haemodynamics did not significantly
      change during anaesthesia. During recovery HR increased and CVP decreased
      significantly. The pHim decreased significantly from 7.42 +/- 0.03 at H0 to 7.30
      +/- 0.02 at H3. This was associated with a significant decrease in pHa (from 7.43
      +/- 0.02 at H0 to 7.33 +/- 0.02 at H3) and in [bicarbo] from 22 +/- 1 mmol at H0
      to 20 +/- 1 mmol at H3). The PaCO2 increased significantly from 33.5 +/- 1.5 mmHg
      at H0 to 39.5 +/- 2.8 at H3. On the other hand, pHimcorr (7.40- (pHa-pHim) and
      delta CO2 (PCO2ss-PETCO2) did not vary during anaesthesia. Postoperative organ
      failure did not occur in these patients. CONCLUSIONS: The pHim may decrease
      during anaesthesia without evidence of abnormal tissue perfusion. In order to
      avoid.

PMID- 9180979
TI  - [Delay of clinical recovery from paralysis induced by atracurium: comparison
      between orbicularis oculi and adductor pollicis].
AB  - OBJECTIVE: To compare with train-of-four stimulation the delays of the beginning
      of the spontaneous recovery of the orbicularis oculi and of the adductor pollicis
      after profound neuromuscular blockade with atracurium. STUDY DESIGN: Prospective,
      comparative open study. PATIENTS AND METHODS: Twenty-eight physical class ASA 1
      and 2 patients under general anaesthesia (propofol, N2O, fentanyl) and profound
      neuromuscular blockade with atracurium. Train-of-four stimulation, every 10 s, of
      the ulnar nerve at the wrist (for assessing by tactile means the response of the
      adductor pollicis) and of the temporal branch of the facial nerve (for assessing
      visually the response of the orbicularis oculi). On each site, measurement of the
      delay between the end of the maintenance of deep neuromuscular blockade (last
      dose of atracurium) and the beginning of the recovery (first response to train-of
      four stimulation). RESULTS: In each case, the recovery of the orbicularis oculi
      began earlier than the recovery of the adductor pollicis (26 +/- 9 min vs 34 +/-
      9 min, P < 0.001). The delays of recovery at each site were strongly correlated
      (r = 0.87; P < 0.001) but the time lag between the responses varied greatly: 1 to
      21 min, mean: 8 +/- 5 min, coefficient of variation: 56.6%. CONCLUSION: The
      orbicularis oculi should not be monitored alone for assessment of recovery from
      profound neuromuscular blockade by atracurium, as it predicts poorly the time of
      the recovery of the adductor pollicis.

PMID- 9180980
TI  - [Intubation conditions: importance of the rate of repetition of the train-of
      four].
AB  - OBJECTIVES: To assess that neuromuscular relaxation onset of the adductor
      pollicis (AP) is related to neuromuscular stimulation rate. To assess that train
      of-four (TOF) at 0.05 Hz is a more accurate indicator of optimal tracheal
      intubation time and conditions, than TOF at 0.08 Hz. STUDY DESIGN: Prospective,
      comparative, randomized double-blind study. PATIENTS: Forty adults, physical
      class ASA 1 or 2, undergoing general anaesthesia with tracheal intubation were
      allocated to two groups (n = 20) according to the sequence of stimulation of the
      AP: either TOF at 0.05 Hz (test group) or TOF at 0.08 Hz (control group).
      METHODS: Induction of anaesthesia was achieved with thiopentone, fentanyl and
      vecuronium (0.1 mg.kg-1). Neuromuscular monitoring was obtained with force
      displacement transducers attached to each AP. Tracheal intubation was performed
      once AP muscular response obtained with TOF at 0.05 Hz for test group and TOF at
      0.08 Hz for control group was abolished. Results are expressed as mean +/- SEM.
      Fisher exact test was used for intubation conditions comparison. Curarization
      time between groups was compared with unpaired Student's t test (P < 0.05
      accepted). RESULTS: TOF with 0.05 Hz stimulation significantly increased
      curarization time: 217 +/- 7 versus 162 +/- 6 s (P < 0.001). Intubation
      conditions were excellent in 95% and good in 5% of patients in the study group,
      compared to 15 and 40% in the control group, respectively (P < 0.01) in 45% of
      the control group patients coughing at intubation occurred. CONCLUSION: Low
      stimulation rate (TOF at 0.05 Hz) of AP is a reliable technique to determine the
      appropriate intubation time for patients paralyzed with vecuronium.

PMID- 9180981
TI  - [Effects of different loading solutions on plasma osmolality].
AB  - OBJECTIVE: As hydratation of the normal brain is much more dictated by osmotic
      gradients than by hydrostatic or oncotic pressures, this study aimed to compare
      the effect of the infusion of currently used volume loading solutions on plasma
      osmolality. STUDY DESIGN: Randomized, comparative trial. PATIENTS: Thirty ASA 1-2
      patients, scheduled for lumbar intervertebral disc surgery were randomly
      allocated to three groups receiving either 2,000 mL of lactated Ringer's solution
      (RL, n = 10), 750 mL of hydroxyethylstarch 6% (HEA, n = 10) or 2,000 mL of normal
      saline (NaCl, n = 10). METHODS: Baseline osmolality, natraemia, glycaemia and
      protidaemia were measured before induction of anaesthesia (T1), after the
      infusion of 375 mL of hydroxyethylstarch or 1,000 mL of crystalloids (T2) and at
      the end of the infusion (T3). RESULTS: The three groups were identical for age,
      weight, initial plasma osmolality and natraemia. However, osmolality in the RL
      group was decreased at T2 and T3 compared to T1 (respectively: 299 +/- 5 mOsm.kg
      1, 295 +/- 4 mOsm.kg-1 and 292 +/- 5 mOsm.kg-1. Osmolality at T2 and T3 was also
      lower in the RL group compared to the HEA and NaCl groups (respectively: 301 +/-
      6 mOsm.kg-1 and 304 +/- 13 mOsm.kg-1 for T2 and T3 in the HEA group, and 299 +/-
      5 mOsm.kg-1 and 298 +/- 5 mOsm.kg-1 in the NaCl group). In the HEA and NaCl
      groups, osmolality was unchanged at T2 and T3 compared to T1. CONCLUSION: Both
      normal saline and hydroxyethylstarch 6% maintain plasma osmolality, whereas
      Ringer lactate tends to decrease it. For that reason normal saline and hetastarch
      6% but not lactated Ringer's solution, may be administered in patients
      experiencing blood-brain barrier damage.

PMID- 9180983
TI  - [Physiology of nociception].
AB  - Nociception is related to the mechanisms elicited by stimuli threatening the
      integrity of the organism. At the peripheral level, unmyelinated C fibres (C
      polymodal nociceptores) or fine myelinated A delta fibres are excited by noxious
      stimulation, directly or indirectly by inflammatory processes. Nociceptive
      afferent fibres terminate in the superficial laminae of the dorsal horn of the
      spinal cord where informations are integrated and controlled. These first
      synapses are modulated by excitatory amino acids (glutamate and aspartate) and
      many peptides (substance P, CGRP, CCK, endogenous opiods). The majority of
      ascending pathways involved in nociception are located in the ventrolateral
      controlateral quadrant of the cord (spinorelicular and spinothalamic tracts).
      Many supraspinal sites are activated following nociceptive stimuli, with relays
      in the reticular formation of the brain stem (including the subnucleus
      reticularis dorsalis), the ponto-mesencephalic regions (periaqueducal gray matter
      and parabrachial area) and thalamic sites. Amygdala and hypothamic targets could
      be involved in motivational reactions and neuroendocrine adaptations to a noxious
      event. The cingular, insular and somatosensory cortices also receive nociceptive
      informations. Nociceptive signals are modulated at all levels of their
      transmission; the more extensively studied controls are located at the spinal
      level. Segmental controls are inhibitory effects produced by non-noxious
      mechanical stimuli. Spinal signals can also be inhibited following activation of
      bulbopinal descending inhibitor pathways and release of serotonin, norepinephrine
      and, indirectly, endogenous opiods. Inhibitory controls triggered by noxious
      stimuli could facilitate the extraction of the nociceptive tone of informations
      having priority over other stimuli.

PMID- 9180982
TI  - [Severity of illness explains the inadequacy between diagnosis-related groups and
      intensive care patients. Groupe GHM].
AB  - OBJECTIVE: To assess the relationship between diagnosis related groups (DRG) and
      severity of illness in intensive care unit (ICU) patients in semf1tical and
      economical terms. STUDY DESIGN: Prospective, multicentric study including 13
      medical and surgical ICUs for adults. MATERIAL: Discharge reports of 3,215 ICU
      admissions including age, gender, diagnosis, organ system failures, length of
      stay (LOS) and severity of illness evaluated with severity scores (SS):
      simplified acute physiological score (SAPS). Apache II, Glasgow score and
      physiological score (PS). METHODS: Semantical homogeneity was evaluated from the
      percentage of well-classified patients established from the comparison between
      the official computerized method and a non-computerized method applied by three
      clinical experts. Economical homogeneity was evaluated from the relationship
      between SS and LOS. RESULTS: In total, 88% (CI: 87.7-88.2) of ICU stays were
      classified in eight main categories of diagnosis (MCD). According to the MCD, the
      percentage of well-classified patients varied from 28% (CI: 27.6-28.3) to 97%
      (CI: 96.8-97.1), decreasing with the association of several diagnoses and organ
      system failures. There was a large variability in the LOS of DRG and a
      significant correlation between LOS and SS was found in only 8/16 DRG.
      CONCLUSION: The fact that the severity of illness is not taken into account in
      the elaboration of DRGs explains the inadequacy of the DRG system in intensive
      care.

PMID- 9180984
TI  - [Pulmonary tuberculosis in 1996. Recent data and practical consequences for the
      anesthesiologist].
AB  - Tuberculosis is one of the most widespread diseases, occurring in more than eight
      million persons, and about three million die annually of tuberculosis. In
      industrialized countries, the incidence has increased significantly over the last
      10 years. HIV infection is a main factor leading to this increase. Outbreaks of
      nosocomial tuberculosis among patients and healthcare workers have been reported.
      Tuberculosis is often caused by multidrug-resistant bacilli in patients with HIV
      infection. Physicians must be aware of this danger and careful adherence to
      guidelines is required to prevent further nosocomial spread of the disease.
      Airborne transmission by inhalation of infectious aerosol justifies appropriate
      measures for respiratory isolation to protect medical staff and other patients
      from the transmission of tuberculosis. In combination with some anaesthetic
      agents, antituberculous drugs may be responsible for hepatic toxicity. Influence
      of tuberculosis on regional anaesthesia and mechanical ventilation is also
      considered.

PMID- 9180985
TI  - [Heart injury following closed thoracic injury].
AB  - A 60-year-old man, was admitted in the emergency ward, following a motor vehicle
      accident. At the time of arrival his clinical state was stable. The initial
      investigations showed a moderate left haemopneumothorax and fractured ribs. After
      insertion of a thoracostomy tube into the left pleural cavity he had to undergo
      surgery for an open fracture of the left arm. Following induction of anaesthesia,
      a cardiovascular collapse occurred rapidly. An emergency thoracotomy was
      performed which showed a right ventricular perforation by a rib fragment. The
      authors discuss the role of possible changes in heart position produced by
      induction of general anaesthesia. Indeed the decrease in functional residual
      capacity following induction of anaesthesia with a cephalad diaphragmatic shift
      may have secondarily exposed the right ventricle to the bevel of a fractured rib.

PMID- 9180986
TI  - [Amiodarone-induced thyrotoxicosis cured by thyroidectomy].
AB  - We report a case of amiodarone-induced thyrotoxicosis, diagnosed with a
      systematic laboratory investigation in a 64-year-old patient, for haematuria.
      Despite the interruption of amiodarone, hyperthyroidism and a goiter occurred.
      Conventional therapy betablockers, antithyroid agents, prednisone, potassium
      perchlorate) did not result in any clinical improvement. The development of a
      malignant thyrotoxicosis with neurologic disturbances and acute respiratory
      insufficiency required mechanical ventilation and a subtotal thyroidectomy. The
      patient's status improved progressively and he was discharged without sequelae.
      The respective roles of medical therapy and thyroidectomy in amiodarone-induced
      thyrotoxicosis are discussed.

PMID- 9180988
TI  - [Three-in-one block or femoral nerve block. What should be done and how?].
AB  - The "3 in 1" block and the femoral nerve block are widely used for lower limb
      surgery and postoperative analgesia. Whether these blocks are in fact a same
      regional block with two different names or represent definitively two different
      blocks remains controversial. A large number of anatomical as well as functional
      variations of the lumbar plexus have been described and complicate a rational
      analysis of the spread of local anaesthetics following these blocks. Anatomical,
      radiological and especially clinical data seem to confirm that these blocks are
      to be distinguished from one another. Femoral nerve block requires the use of a
      nerve stimulator and has a high success rate in the territory of the femoral
      nerve; a spread towards other lumbar nerves, especially the lateral femoral
      cutaneous nerve, is sometimes observed. The "3 in 1" block is supported by the
      idea of diffusion within a space that is located after going through two fascial
      layers. Even in experienced hands, the success predictive value is not high.
      However, once the "3 in 1" block is well performed, a complete anaesthesia
      covering the territories of the femoral nerve, the lateral femoral cutaneous
      nerve, and the obturator nerve occurs. Specific indications of each technique are
      different: major knee surgery and postoperative analgesia for the "3-in-1" block
      and leg surgery for femoral nerve block. The best approach for knee arthroscopy
      remains open for discussion.

PMID- 9180987
TI  - [Lyell syndrome after amoxicillin administration in a 2 year old child].
AB  - The authors report a toxic epidermal necrolysis (TEN) due to ampicillin (Agram)
      in a 2-year-old child. During the acute phase a septic syndrome occurred. The
      severity of the clinical and biological symptoms led to the administration of
      antibiotics, their systematic use remaining controversial. Recovery was
      favourable in a paediatric burn centre. Sequelae were minor. TEN, the
      physiopathological mechanism of which remaining still unknown, may carry a vital
      risk.

PMID- 9180989
TI  - [A study of pneumatic performances of 2 new anesthesia ventilators: a trial].
AB  - OBJECTIVE: To assess the pneumatic performance of two new anaesthesia
      ventilators. STUDY DESIGN: Test bench study. MATERIAL: ADU (Datex), Excel 7900
      (Ohmeda) ventilators both included in "bellows-in-box" class, with rising bellows
      at expiration. METHODS: The accuracy of spirometry and pressure measurements was
      tested in various conditions of downstream charge and ventilation. The bench
      comprized a passive lung model with adjustable compliance and resistances, and
      flow and pressure gauges. RESULTS: Pneumatic performance and accuracy were good
      in normal as well as in severe ventilatory conditions. This is made possible by
      the compensation algorithm included in these machines, which automatically
      corrected the delivered volume for errors related to tubing and gas
      compressibility. CONCLUSION: These two new machines with pneumatic compensation
      overcome the main drawback seen with conventional "bellows-in-box" ventilators.

PMID- 9180990
TI  - [1846-1847: starting inhalation anesthesia in Paris].

PMID- 9180991
TI  - [Evaluation of direct theoretical cost of passage in anesthesia recovery room].
AB  - OBJECTIVE: To assess the direct cost of a stay in a postanaesthesia care unit
      (PACU). STUDY DESIGN: Standard cost study based on information gathered from
      staff and suppliers in accordance with government regulations and
      recommendations. Results reviewed by a group of anaesthesists. TYPE OF PACU: PACU
      working in ideal conditions with optimal safety conditions for and accommodation
      surgical patients). METHOD: Estimation of three cost components: 1) depreciation
      and maintenance costs of equipment, 2) physician and other staff wages, and 3)
      variable costs such as drugs and disposable devices. We computed an annual budget
      for three PACU which was defined according to size (4, 8 or 12 beds) and working
      hours. RESULTS: Fixed annual costs (staff and equipment) were 1,134,938 FF for a
      4 bed room: 3,820,339 FF for an 8 bed room: and 6,481,792 FF for a 12 bed room.
      Variable costs per stay were 75,43 FF. The cost of a stay in an 8 bed PACU based
      on a rate of 3,500 stays per year therefore was 1,167 FF (87.0% for staff, 6.6%
      for equipment, 6.4% for variable costs).

PMID- 9180992
TI  - [Transfusion and Jehovah's witnesses. A review of medicosurgical attitudes in a
      University hospital in 1995].
AB  - The aim of this study was to evaluate the attitudes of physicians (anaesthetists
      + other doctors + surgeons) towards Jehovah's witness patients refusing blood
      transfusion. Such a situation is not uncommon: 79% of respondents uncountered it.
      For scheduled surgery in adults, 75% of these physicians (54% of anaesthetists)
      would accept to lake care of these patients. In case of emergency or unforeseen
      indication for transfusion, 54% of these physicians (72% of anaesthetists) would
      administer blood, despite a written transfusion refusal. These figures would be
      95 and 97% respectively in children.

PMID- 9180993
TI  - [Role of albumins in burnt patients: its efficacy during intensive care. Addendum
      to the expert guidelines of the Consensus Conference, Paris December 15th 1995].
AB  - In the burned patient, the critical threshold over which a correction of
      hypoalbuminemia is required has not yet been clearly defined. The level of 30 g.L
      1 of albumin is usually admitted. According to the extent of the burn, albumin is
      not indicated in patients with a burn size below 15% of the total body surface.
      It is essential, from the very beginning of management in patients with a burn
      size over 50%. Its administration can be postponed to the 8th, 12th or even 24th
      hour in case of a burn size between 15 and 50%.

PMID- 9180994
TI  - [Transfusion and early infections in surgery].

PMID- 9180995
TI  - [Unit of pain treatment in pediatrics. An experience over 2 years in a pediatric
      hospital].

PMID- 9180996
TI  - [Postoperative analgesia, self-controlled by aged patients].

PMID- 9180997
TI  - [Ventriculoperitoneal shunt and colonic obstruction].

PMID- 9180998
TI  - [Arrhythmia during the recovery phase in a child. Another ampoule story, a human
      error...].

PMID- 9180999
TI  - [Combined spinal and epidural analgesia for labor].

PMID- 9181000
TI  - [Transfer hypokalemia in a head injured patient].

PMID- 9181001
TI  - [Endocrine theory of idiopathic nocturnal enuresis].
AB  - Body fluid homeostasis is maintained by the kidney. Such an accurate control in
      achieved via the secretion of antidiuretic hormone (ADH), the secretion of which
      is regulated by hypothalamic osmoreceptors. Both urine flow rate and the
      excretion of most electrolytes have a diurnal rhythm; they increase during
      daytime and decrease during nighttime. Such a rhythm seems to be absent in some
      subjects who suffer from bedwetting because of relative polyuria. In these cases,
      the polyuria is associated with a decreased nocturnal secretion of ADH and the
      subsequent excretion of dilated urine. A deficit in the nocturnal secretion of
      ADH thus appears to explain the response to desmopressin of children with a
      polyuric form of enuresis.

PMID- 9181002
TI  - [Differences in the profile of nycthemeral diuresis].
AB  - Monosymptomatic enuresis in childhood can be divided in two subtypes by a
      nycthemeral diuresis profile, including urinary volume and osmolality. The first
      one is characterized by an abnormal circadian diuresis cycle, responsible for
      nocturnal polyuria and/or low urinary overnight osmolality, there is a good
      response to desmopressin; the other one is the so-called cognitive or idiopathic
      type, which provides a poor response to desmopressin.

PMID- 9181003
TI  - [Urination disorders revealing posterior urethral valve: clinical aspects].
AB  - One hundred sixty-four boys presenting with voiding dysfunction without any
      obvious uropathy or neuropathy were enrolled in a prospective study. Nine (5.5%)
      were suspected to have urethral valves after video-urodynamic assessment, later
      confirmed by cystoscopy. Those with proven posterior urethral valves were
      compared to a control group of boys without urethral obstruction. There was no
      difference in anamnesis nor clinical presentation between the two groups. Even on
      uroflowmetry the urethral valves were not suspected; only the urodynamic
      assessment could distinguish the obstructed from the non-obstructed boys.
      Although there remains controversy about the existence of posterior urethral
      valves in functional voiding disorders in boys, we could demonstrate that after a
      complete prospective screening such a rare combination occurs in around 5% of the
      cases.

PMID- 9181004
TI  - [Urination disorders revealing posterior urethral valve: radiological aspects].
AB  - Posterior urethral valves represent the most common form of congenital urethral
      obstruction; they are due to the presence of membranous recesses within the
      posterior urethra. Their consequences on the lower and upper urinary tract depend
      on the importance of the obstacle. Moderate forms have a late clinical onset in
      children who present with voiding disorders and a normal upper urinary tract; in
      such cases, the diagnosis is difficult since typical features are absent on the
      urethrocystogram. Radiological signs of urethral valves should be differentiated
      from congenital urethral strictures which are not obstructive and from bladder
      dysfunctions which modify both the bladder and the urethra during micturition.

PMID- 9181005
TI  - [Urination disorders revealing posterior urethral valve: urodynamic aspects].
AB  - Urodynamics include several investigations of the bladder-sphincter complex.
      Uroflowmetry is easy to perform but interpretation might be hazardous in very
      young children: in urethral obstruction, it shows a decrease in the maximal flow
      rate and an increase in the voiding time: such an investigation has no specific
      value in case of posterior urethral valves since it can be even normal in case of
      obstruction. Nevertheless, uroflowmetry is of great interest with respect to
      postoperative follow-up. Other investigations of the bladder and of the urethra
      are more aggressive and not so helpful in diagnosing obstruction: they might be
      helpful in understanding and managing persistent voiding disorders after
      posterior urethral valves section.

PMID- 9181006
TI  - [Endoscopic aspects of posterior urethral valve].
AB  - Most congenital posterior urethral valves arise from the urethral crest, just
      below the veru montanum. Urethral diaphragms have been well identified but the
      concept of valves running from the vern to the bladder neck is questionable.
      Despite advances in non-invasive investigations, the accurate identification of
      urethral valves can be achieved only by endoscopy. Such an exploration is
      required to define the mechanism of urethral obstruction and therefore to provide
      an appropriate endoscopic treatment. The age, the clinical condition of the child
      and the size of his penis and meatus might sometimes delay urethral endoscopy for
      some months in order to avoid secondary urethral stenosis.

PMID- 9181008
TI  - [Posterior urethral valve: determining factors of long-term results].
AB  - Posterior urethral valves (PUV) is the most common congenital urine flow
      impairment in boys. Long-term prognosis involves: renal function impaired in 30
      to 50% of PUV and leading to hyperdiuresis, low GFR and acidosis; bladder
      urodynamics impaired in 75% of PUV with abnormal urine storage, abnormal
      micturition and vesicoureteric reflux. Incontinence and recurrent urinary tract
      infections commonly reflect bladder and renal failures; abnormal bladder outlet
      leads to incontinence and abnormal ejaculation. The roles of antenatal treatments
      (vesico-amniotic shunts), neonatal treatments (resuscitation and endoscopic
      treatment of PUV) and long-term treatments (urinary diversions, bladder
      augmentation, alpha blockers, anticholinergic, dialysis and renal transplant) in
      the long-term outcomes of PUV are reviewed.

PMID- 9181007
TI  - [Persistent urination disorders after treatment of posterior urethral valve:
      incidence and semiology].
AB  - Micturition disorders were studied retrospectively in a series of 165 children
      over a period of 15 years. Among patients without lesions of the upper tract at
      the time of diagnosis (group A, n = 131), 18 (14%) had persistent nocturnal and
      diurnal enuresis: one urethral stenosis and six vesicoureteric reflux required
      surgery; three experienced persistent pollakiuria and enuresis. Among patients
      with upper urinary tract damage at the time of diagnosis (group B, n = 34), seven
      presented with recurrent urinary tract infection, five with nocturnal and diurnal
      enuresis and three with urolithiasis. In the long term, only 52% of them had
      normal renal function and two were successfully transplanted. Micturition
      disorders following treatment of posterior urethral valves are frequent and
      usually related to the so-called valve bladder syndrome. Iatrogenic complications
      and mortality rate have dramatically decreased during the recent years but long
      term renal function impairment remains the most critical problem.

PMID- 9181009
TI  - [Urination disorders and neurological disease except for o obvious medullary
      pathology: perinatal brain lesions with mental handicap].
AB  - Children with mental retardation often present urinary incontinence because they
      are unable to control micturition. Constipation and/or encopresis are often
      associated. Careful assessment of the upper urinary tract and renal function is
      indicated. Urinary infections are frequent, however, bladder dysfunction
      complications of the upper urinary tract are uncommon. The cause of wetting could
      be explained by urodynamic findings: small capacity bladder with uninhibited
      contractions, hypertonic sphincter, or incomplete emptying secondary to detrusor
      sphincter dyssynergia. Treatment of urinary incontinence should be adapted to the
      type of incontinence and be apart of the global training.

PMID- 9181010
TI  - [Urination disorders in patients with sequelae of perinatal lesions without
      mental handicap].
AB  - Sixty-three patients with cerebral palsy and micturition disorders were
      investigated. The age ranged between 5.5 and 38 years (mean 13.5). Half had
      diplegia: one-third had quadriplegia and were therefore dependent incontinence
      was the most common symptom: dysuria was noted in half of the cases, mainly in
      quadriplegic patients. The urodynamic assessment confirmed the dysfunction and
      showed hyperreflectivity with or without asynergy. However, no therapeutic
      approach has been validated.

PMID- 9181011
TI  - [Enuresis "as a hindrance for entering nursery school"].
AB  - Diurnal enuresis is very uncommon and may be related to early onset parent-to
      child relationship disorders. As a symptom, enuresis can hinder nursery school
      socialization or can arise at this time. Two case-reports illustrate such an
      hypothesis.

PMID- 9181012
TI  - [Is systematic screening of asymptomatic celiac diseases justified?].

PMID- 9181013
TI  - [Bacteriological study in acute otitis media].
AB  - AIM: A prospective study on bacteriological epidemiology in acute otitis media
      was conducted in a pediatric hospital emergency service from January 1993 to
      October 1995. PATIENTS: One hundred and fifty-eight children, aged 6 months to 6
      years, with an acute otitis media were included. Culturing and cleansing of the
      ear canal and tympanocentesis for aspiration and culture of the secretions were
      performed in 118 children (46 of whom had received antibiotics before for 48
      hours). MAIN RESULTS: Middle ear aspirates were sterile in 35% of the children
      who had not received antibiotics and in 64% of those already treated. Bacteria in
      middle ear were predominantly Haemophilus influenzae and Streptococcus
      pneumoniae. Fifty-nine percent of S pneumoniae strains were penicillin-resistant;
      however, they were responsible for clinical failure in only 8% of cases. No
      Staphylococcus strains, commensal of the ear canal, could be considered as
      pathogenic for the middle ear. CONCLUSION: The preciseness with which secretions
      of middle ear are aspirated reduces the risk of contamination and comparison of
      ear canal and middle ear cultures allows to identify them. The high ratio of
      sterile middle ear aspirates after antibiotic treatment raises the question if
      other factors are responsible for persistent symptoms. The existence of
      penicillin-resistant S pneumoniae must be known to adjust treatment.

PMID- 9181014
TI  - [Influence of the transfer mode on short-term outcome in neonates with high
      perinatal risk].
AB  - BACKGROUND: Transferring in utero children with high perinatal risk has been
      widely recommended in France over the last few years. The purpose of this study
      is to describe the different transfer modes for children less than 32 weeks GA or
      less than 1,500 g birthweight and analyse their impact on death and severe
      neurological lesion. POPULATION AND METHODS: This retrospective study concerned
      live births in a definite geographic area (Lorraine, France). Four hundred and
      twenty-seven children born alive between 1989 and 1992 and hospitalized in eight
      neonatology units were recruited. Multivariate analysis (logistic regressions)
      were performed to assess the influence of transfer mode on death or severe
      neurological lesion. RESULTS: Sixty-two percent of the children were born in the
      level 3 maternity, 19% in a level 1 maternity and 19% in a level 2 maternity. One
      hundred and twenty-one children (28%) were transferred in utero and 116 (27%)
      were transferred extra muros. Thirty children died during the hospital stay.
      Multivariate analysis does show that neonatal extra muros transfer plays a
      significative role on neonatal death after adjustment for other risks factors (OR
      = 3.3 (1.1-9.91). Thirty-one children presented a severe neurological lesion. In
      comparison with neonates born in the level 3 maternity without transfer, extra
      muros transfer appears to be a very significant risk factor (P = 0.0008): OR for
      transfer from level 2 and level 1 maternity is 15.8 (3.8-66.5), and 5.6 (1.3-24)
      respectively. There is no significant increased risk for children born after
      maternal transfer or born in a level 2 maternity without transfer. CONCLUSION:
      These data are consistent with data from the literature and confirm the risk
      related to extra muros transfer in premature babies less than 32 weeks GA or less
      than 1,500 g birthweight.

PMID- 9181016
TI  - [Is a 11-year-old tennis player indifferent to competition stress?].
AB  - BACKGROUND: In adults, competition generates a relatively important level of
      stress. This could be revealed by psychological questionnaires and adrenocortical
      responses. This study was aimed to evaluate the load of stress in young tennis
      players in situations of competition compared to that observed during a training
      session. POPULATION AND METHODS: The 16 best young tennis players of the Auvergne
      area (mean age: 10.9 +/- 1.7 years) entered the study. The degree of anxiety was
      measured with the aid of the Martens' SCAT questionnaire and the result of
      salivary cortisol testing during a training session, and after each of the three
      competition rounds of the Auvergne championship (three samples were collected at
      each time: at rest, before and after exercise. RESULTS: Regarding the degree of
      anxiety, no significant difference was found between the competition and the
      training session. Cortisol levels did not change during the training session:
      during the competition, same moderate increase (less than 50%, P < 0.05) was
      noted for the first two rounds between rest and post-competition values. No
      difference was found at the third round. CONCLUSION: The high levels of stress
      described in adults are not found in young tennis players.

PMID- 9181015
TI  - [Fragile X syndrome is still unrecognized: efficacy of molecular diagnosis in
      mentally retarded probands].
AB  - BACKGROUND: The fragile X mental retardation syndrome is the most common cause of
      inherited mental retardation. Identification of the unstable mutation responsible
      for the disease has allowed the design of a fully reliable molecular test for the
      diagnosis of the disease and for genetic counselling (identification of
      clinically normal carriers and prenatal diagnosis). We started in July 1991 to
      search for the mutation in mentally retarded probands, with no known cause for
      their phenotype. We present the results of a 42-month experience. POPULATION AND
      METHODS: One thousand and one hundred fourty-nine probands were analysed. In case
      of a positive diagnosis, an extension of the molecular study to relatives was
      proposed. DNA samples were studied by Southern blot following EcoRI or EcoRI +
      EagI digestion. Clinical data were collected from referring clinicians. RESULTS:
      Seventy-three carriers of a full mutation were identified, belonging to 52
      families. The mean age of the fragile X probands was 16 +/- 14 years, which is
      very surprising for a disease that causes significant manifestations by the age
      of 2 to 3 years. This indicates an insufficient knowledge about this disease in
      France. Most of the demands for the test were from clinical geneticists. This
      diagnosis is of major importance for genetic counselling, as illustrated by the
      following study of 108 women at risk in these families. CONCLUSIONS: The
      importance of an early diagnosis followed by an extended family study, for
      carrier screening and prevention of this severe disease, justifies molecular
      testing on any child with mental retardation or significant language delay of
      unknown cause, in the absence of clinical signs formally excluding a fragile X
      diagnosis.

PMID- 9181017
TI  - [Antineoplastic chemotherapy and Wernicke's encephalopathy].
AB  - BACKGROUND: Wernicke's encephalopathy is usually seen in alcoholic adults. It is
      rare in childhood and usually discovered in a context of several pathological
      events. We report here a typical case of a teenager. CASE REPORT: A 15-year-old
      girl with acute leukemia was given chemotherapy that resulted in profound aplasia
      and serious infection. She exhibited abnormal eye movements, ataxia, lethargy,
      enuresis and amnesia. MR examination showed T2-weighted images with increased
      signal in the thalami (pulvinar) and periaqueducal region. The symptoms improved
      dramatically with thiamine therapy. Omission of the usual vitamin supplementation
      between the courses of chemotherapy was responsible for this encephalopathy.
      CONCLUSION: Thiamine deficiency can lead to death or amnesia. Rapid efficacy of
      vitamin supplementation helps diagnosis and prevents sequelae.

PMID- 9181018
TI  - [Congenital toxoplasmosis with hydrocephalus diagnosed in utero: outcome of
      treatment].
AB  - BACKGROUND: The neurological outcome for severe toxoplasmosis can be poor despite
      appropriate management. CASE REPORT: A maternal toxoplasma infection occurred at
      16 weeks of amenorrhoea; prenatal diagnosis was attempted at 20 weeks, fetal
      infection was confirmed by mouse inoculation at the 30th week. Pyrimethamine plus
      sulfadiazine treatment was initiated. However, at 37 weeks of amenorrhoea,
      sonographic examination of the fetus detected hydrocephalus. Despite prompt
      ventriculo-peritoneal shunting after birth and medical treatment of
      toxoplasmosis, the neurological developmental outcome was complicated and
      prognosis is poor at 5 years of age. CONCLUSION: This case shows that parents
      must be carefully warned about risks of a prenatal toxoplasmosis.

PMID- 9181019
TI  - [Hepatoportal sclerosis: apropos of a familial case].
AB  - BACKGROUND: Hepatoportal sclerosis is uncommon in European countries and its
      diagnosis is difficult. The etiology remains unknown; its familial origin is
      probably exceptional. CASE REPORT: An 18-month-old girl born to a mother with
      hepatoportal sclerosis had hepatomegaly. She also had a moderate splenomegaly and
      mild increase transaminase and gamma GT activities. Ultrasound examination failed
      to show portal hypertension. Histological study of liver showed changes quite
      similar to those seen in her mother. Two members of the mother's family had
      portal hypertension. DISCUSSION: Familial forms of portal hypertension have been
      reported: a familial form of incomplete septal cirrhosis and a familial
      occurrence of cavernous transformation of the portal vein. Obstruction of the
      portal vessels was not found in our patient, the youngest in whom hepatoportal
      sclerosis is documented.

PMID- 9181021
TI  - [Neonatal meningitis caused by Alcaligenes xylosoxydans].
AB  - BACKGROUND: Neonatal meningitis due to Alcaligenes xylosoxydans is exceptional;
      its diagnosis and treatment may be difficult. CASE REPORT: A neonate born at 42
      weeks of GA to a mother who worked as a nurse in an intensive care unit was
      admitted on day 2 for a severe infection. Her cerebrospinal (CSF) contained 1,970
      white cell/mm3, polymorphonuclear in majority: direct examination failed to show
      any germ but the CSF and blood cultures were positive for Alcaligenes
      xylosoxydans, a strain that was resistant to the initially given antibiotics. The
      patient was given piperacillin, 300 mg/kg/d for 21 days and completely cured with
      a follow-up of 6 months. CONCLUSIONS: This case shows that lombar puncture can be
      necessary in evaluating early neonatal sepsis; it also shows usefulness of
      piperacillin in some cases.

PMID- 9181020
TI  - [Ectopic intraspinal extradural anaplastic ependymoma in an infant].
AB  - BACKGROUND: Ependymomas represent about 10% of the spinal tumors in children.
      Some of them may be unusually located. CASE REPORT: A 10-month-old boy was
      admitted for an abdominal mass syndrome with dehydration asthenia and acute
      bladder dysfunction. A few hours later, he developed a flaccid paraplegia.
      Ultrasonic and magnetic resonance spinal imaging showed a giant intraspinal tumor
      extending from T9 to IA level, posteriorly located to the dural compartment,
      widening the spinal cord. Ultrasonography also showed right ureterohydronephrosis
      due to the neurological bladder dysfunction. A conservative laminotomy
      laminoplasty was performed in emergency. Total removal of the tumor that was
      attached to the right dorsal root was achieved extradurally, requiring resection
      of the proximal part of the root. Histological features were typical of malignant
      ependymoma. Chemotherapy was initiated 2 weeks later. The severe renal
      destruction and the persistent bladder dysfunction led to a heminephrectomy and a
      cystostomy, 3 weeks later. The neurological recovery was only partial with a
      follow-up of 18 months. CONCLUSION: Ectopic intraspinal extradural localization
      of ependymomas is rare and their development from a nerve root is exceptional.

PMID- 9181022
TI  - [Management of drug addict pregnant women and their children].
AB  - Children of substance abuse mothers have an increased risk of severe pathological
      disorders such as perinatal diseases (prematurity, intrauterine growth
      retardation, infections) with their neurological and respiratory complications
      and sequelae, and transmission of drug addiction related infections, ie human
      immunodeficiency virus, hepatitis B and C virus, syphilis. Many of these children
      present a drug withdrawal syndrome characterized by restlessness and jetteriness
      during the neonatal period. This is frequently followed by a post withdrawal
      period of several weeks duration with crying, excitement, sleep and feeding
      difficulties. Although these drug withdrawal manifestations have no incidence on
      the vital prognosis, it severely impairs the mother-infant interaction. Despite
      these disorders it appears that the outcome of these children is mainly related
      to their familial environment which is exposed to many risk factors: mother-child
      separation, violence, delinquency, precariousness, unhealthy housing,
      prostitution, drug dependency, parental death or imprisonment... Early medico
      psycho-social intervention starting during pregnancy and a prolonged support for
      several years are the only way to improve their spontaneously poor outcome.

PMID- 9181024
TI  - [Radiological case of the month. A case of incidental discovery of thoracic
      neuroblastoma].

PMID- 9181023
TI  - [Treatment of pain in children burns].
AB  - Burn injury is considered by children as one of the most painful traumas (just
      after bone factures). Burn pain in children can and must be controlled as well as
      for adult patients, with almost identical techniques. Continuous pain from injury
      and intermittent pain caused by therapeutic procedures must be evaluated and
      treated separately. Due to very high levels of nociception, satisfactory
      management of procedural pain requires the use of opioid therapy. Non
      pharmacological methods are meaningless if pharmacological treatment is not
      optimal.

PMID- 9181025
TI  - [Apropos of the risk of rehospitalization of low birth weight infants].

PMID- 9181026
TI  - [Embryo-fetopathy due to valproate].

PMID- 9181027
TI  - [Analgesia controlled by the patient in pediatrics].

PMID- 9181028
TI  - [Continuing education of the cardiologist].

PMID- 9181029
TI  - [Venous thromboembolic disease and occult cancers: what investigations should be
      done? Apropos of 204 patients].
AB  - There is no consensus about the investigations which should be performed to
      detect occult malignancy after an episode of venous thromboembolism. The authors
      studied 204 patients (167 in-patients and 37 day hospital patients) with deep
      venous thrombosis or pulmonary embolism to determine the incidence of cancers
      detected during or after the thrombosis and the diagnostic value of abdomino
      pelvic ultrasonography. Of the 167 in-patients, 18 (10.7%) had a known
      malignancy. After the initial investigations, 7 tumours were detected (4.6%). In
      all cases, clinical history and examination or chest X-ray were suggestive of
      neoplasia. Abdomino-pelvic ultrasonography did not detect any cases of occult
      malignancy. Of the 37 patients seen in the day hospital, only one had known
      malignant disease and no other cases were detected. After exclusion of the 26
      patients with known malignancies or tumours discovered after the initial
      investigations, the remaining 178 patients were followed up for an average of 27
      months. Four cancers (2.5%) were detected in this period. The authors conclude
      that the occurrence of deep venous thrombosis should lead to investigation for
      malignant disease: clinical examination, chest X-ray and laboratory tests are
      sufficient to orientate this investigation. Systematic abdominopelvic
      ultrasonography does not seem to be worthwhile in this indication.

PMID- 9181030
TI  - [Dynamic three-dimensional cardiac reconstruction by transesophageal
      echocardiography. A clinical experience apropos of 100 cases].
AB  - Three-Dimensional (3D) echocardiography was performed during routine
      transesophageal examinations in 100 patients to identify the most promising
      applications. The approach used was based on the integration of multiple two
      dimensional images recorded with a multiplane probe to achieve 3D reconstruction.
      A series of 90 cardiac cycles was recorded from a fixed position during computer
      controlled rotation of the transducer. The images were digitized, then
      reorganized according to their spatial and temporal location. The cardiac
      structures were then represented dynamically in three dimensions. In 100 patients
      referred for transesophageal echocardiography, the 3D reconstruction provided
      good quality images, under new angles, such as the view of the atrial aspect of
      the mitral valve as seen from the roof of the left atrium. This method was
      particularly well suited to assess mitral valve prolapse or stenosis. The spatial
      extent, direction and number of jets of mitral regurgitation were easily
      appreciated throughout systole, as were the regurgitant jets of mechanical
      prosthetic valves. However, the sensitivity of the 3D method was not as good as
      2D echocardiography for detecting bacterial vegetations in cases of infective
      endocarditis. On the other hand, the determination of the precise localization of
      infectious, degenerative and tumoral lesions and their size were facilitated by
      3D reconstruction. The authors conclude that 3D echocardiography is applicable in
      routine practice and the complementary information provided in certain cardiac
      diseases should help management of these patients.

PMID- 9181031
TI  - [Predictive factors of coronary restenosis after optimal directional atherectomy.
      A multivariate analysis apropos of 102 patients].
AB  - The authors studied 102 patients prospectively who were undergoing coronary
      atherectomy optimised by balloon dilatation in order to assess the restenosis
      rate at 6 months. The coronary lesions were measured in a reproducible manner by
      quantitative angiography. The vessels dilated were the left anterior descending
      in 66 patients and the right coronary artery in 36 patients. The reference
      diameter was on average of 3.57 +/- 0.64 mm. Atherectomy increased the minimal
      diameter of the lesion of 1.20 +/- 0.44 to 3.01 +/- 0.44 mm giving a residual
      stenosis of 15 +/- 11%. At six months, 25% of patients had developed a restenosis
      (> 50% stenosis) with a residual lumen of 2.15 +/- 0.77 mm. The predictive
      factors of restenosis were the initial absolute gain, the length of the lesion,
      the reference diameter of the vessel and the presence of an endoluminal thrombus.
      In multivariate analysis, a small initial gain (p < 0.02) and length of stenosis
      (p < 0.02) were independently correlated with restenosis. The authors conclude:
      1) that optimal atherectomy is associated with acceptable restenosis rates in
      selected vessels, 2) that short stenoses of large diameter arteries may be a
      privileged indication of the technique if the best results are obtained.

PMID- 9181032
TI  - [Contribution of self-surveillance of the personnel by electronic radiation
      dosemeters in invasive cardiology].
AB  - The methods of surveillance of coronary angiography or angioplasty operators vary
      from team to team. The choice of method implies evaluation of the level of
      exposition of unprotected areas. The usual methods of surveillance by dosimetry
      may be complemented by an electronic device used for industrial radiological
      protection against X and Gamma rays. This instrument emits a sound each time a
      micro sievert is detected: the operator perceives the photons of diffused rays.
      The value of protective screens is then directly audible. This instrument does
      not detect X rays with an energy of less than 50 KeV but there is a good
      correlation with results measured by thermoluminescent dosimetry. The measurement
      of irradiation were noted at three points on the body before and after the use of
      complementary protection which certain operators hesitated to use before this
      study. The results confirmed the value of these protections: the suspended lead
      screen reduced cervical irradiations by a factor of 15 and that of the left wrist
      by 8. Lower down, a flexible lead skirt reduced irradiation of the ankle by a
      factor of 19. These results underestimate the efficacy of the screen as low
      energy X rays were not measured and are even more easily absorbed by the screens.

PMID- 9181033
TI  - [In coronary surgery can both internal mammary arteries be used systematically?
      Apropos of 560 patients].
AB  - The grafts commonly used in coronary bypass surgery are the left internal mammary
      artery and the saphenous veins of the legs: the use of both internal mammary
      arteries, with potential long-term benefits, is only justified if the operative
      risk is not increased. Since 1987, the authors use both internal mammary arteries
      systematically in patients under 70 years of age and in good general condition.
      The retrospective analysis of 560 patients having undergone this surgery from
      1987 to 1994 was undertaken to determine if this surgical option is justified
      without increased operative risk. The dissection of the mammary arteries is
      performed in a special manner by skeletonization technique. The total hospital
      complication rate was 12% with 9 deaths in the first 30 postoperative days
      (1.6%). Mediastinitis was observed in 6 patients (1.1%) Early angiographic
      controls showed a patent mammary graft rate of 98%. The use of both internal
      mammary arteries does not therefore increase postoperative morbidity or
      mortality. It may be proposed systematically in patients in good general
      condition and may provide long-term benefits in graft patency rates.

PMID- 9181034
TI  - [Late complications of percutaneous closure of atrial septal defects with the
      Sideris occluder].
AB  - Between June 1992 and January 1996, 27 patients aged 3.9 to 74 years with an
      ostium secundum (22 patients) or patent foramen ovale with right-to-left shunts
      (5 patients) underwent percutaneous closure of their atrial septal defects with
      the Sideris occluder. After a thromboembolic complication, transesophageal
      echocardiography was performed routinely after the procedure in 15 patients
      between 1 month and 2 years, and in 6 patients on the 15th day. Two patients
      died, on the 2nd day and 21st month, of non-related causes. After an average
      follow-up of 33 months, 59% of patients had complete occlusion of the atrial
      septal defects or only a minimal residual shunt. Displacement of the prosthesis
      was defects or only a minimal residual shunt. Displacement of the prosthesis was
      observed in 7 cases with no relationship to size: 4 parallel to the septum with
      reappearance or increase in shunt, 3 with tilting of the prosthesis. All of these
      patients had a large residual defect compared with 20% with a normally positioned
      prosthesis (p < 0.05). Tilting of the occluder was associated with left atrial
      thrombosis (present in 40% of these patients), complicated by systemic embolism
      in one case: there were no cases of left atrial thrombus in the 9 with complete
      occlusion and the 5 patients with an isolated residual defect (p < 0.05).
      Occlusion of atrial septal defect with the Sideris device is effective and a safe
      method in the majority of cases. However, a badly positioned prosthesis with a
      residual shunt should be extracted as seen as possible or within three weeks if
      displacement is observed at control echocardiography.

PMID- 9181035
TI  - [Implantation of coronary stent during the acute phase of myocardial infarction
      for treatment of dissection or partial result after angioplasty. Immediate
      results and angiographic follow-up].
AB  - Between December 1991 and November 1994, a Palmaz-Schatz stent was implanted in 9
      patients aged 57 +/- 14 years during the acute phase of myocardial infarction
      after primary angioplasty in 7 cases and salvage angioplasty in 2 cases after an
      interval of 175 mm +/- 62 mn from the onset of infarction, because of threatening
      dissection (N = 8) or a partial result (N = 1). The success rate of implantation
      was 100% with residual stenosis (DCI Philips system) measured at 16 +/- 8% (5 to
      28%). Anticoagulant treatment comprised heparin, coumadin and aspirin in two
      cases, and, in the following 7 cases, low molecular weight heparin, ticlopidine
      and aspirin. There was one death due to cardiogenic shock on the third day
      despite intraaortic balloon pumping. One patient was operated for a femoral
      aneurysm. A prophylactic bypass procedure was performed as a semi-emergency in a
      stable patient. At systematic angiographic control, the residual stenosis was
      measured at 19 +/- 14% (10 to 43%) without reocclusion. There was no recurrence
      of ischaemia. The authors conclude that the encouraging results of this short
      series suggest that despite the highly thrombogenic situation of acute myocardial
      infarction and despite the context of emergency implantation of a stent. Palmaz
      Schatz stent implantation gives good immediate and long-term results with respect
      to reocclusion and stenosis.

PMID- 9181036
TI  - [Changes in cardiac function during recreational diving].
AB  - Underwater diving is a widely practised leisure activity. As cardiac patients may
      wish to participate, cardiologists should be aware of potential changes of
      cardiac function during diving. Multiple factors may affect haemodynamics.
      Firstly, changes in pressure, secondary to ventilation of a high density gas
      mixture which increases afterload. Hyperoxia is the principal factor which slows
      the heart rate, a commonly observed phenomenon. Excitability and conduction speed
      may be modified by the increase in hydrostatic pressure. During decompression,
      gaseous pulmonary embolism may increase right heart pressures and cause a
      paradoxical embolism may increase right heart pressures and cause a paradoxical
      embolism in patients with a right-to-left shunt. Immersion increases the preload.
      Exposure to cold also plays a role increasing afterload and slowing the heart
      rate. These factors may disturb cardiac function and expose cardiac patients to
      accidents during underwater diving.

PMID- 9181037
TI  - [Guidelines of the French Society of Cardiology for practice of cardiac
      rehabilitation in adults].

PMID- 9181038
TI  - [Giant aneurysm of the interventricular septum. Value of imaging techniques].
AB  - A pseudosubaortic left ventricular aneurysm was discovered in a 32 year old
      African presenting with pyrexia after a long history of chest pains and dyspnea.
      Echographic and radiological techniques showed a large pulsatile mediastinal mass
      and the patient was referred for aneurysmorrhaphy. The actiology of this pseudo
      aneurysm is discussed with reference to data in the literature. Infection is the
      first cause to be excluded in view of the pyrexia truncated by "blind" anti
      inflammatory and antibiotic therapy. The hypothesis of an interventricular septal
      abscess secondary to septicaemia with secondary rupture into the pericardium is
      discussed. Precessive endocarditis with an aseptic abscess is unlikely because of
      the minimal aortic valve lesions, the absence of vegetations and the very long
      clinical evolution. Finally, idiopathic pseudo-aneurysms in sub-Saharian
      Africans, due to a congenital defect of the fibrous aortico-mitral and subannular
      zones must be considered. The risk of complications of these pseudo-aneurysms
      justifies surgical intervention on the accurate anatomical description of the
      lesions provide by transthoracic and transoesophageal echocardiography and
      magnetic resonance imaging.

PMID- 9181039
TI  - [Intrabronchial migration and extraction of a fragment of an Accufix J-shaped
      atrial pacing catheter].
AB  - The authors report a case of exteriorisation and migration of a fragment of a J
      shaped atrial Accufix Telectronix (Stimarec Class IV) responsible for a bronchial
      penetration without clinical repercussion. A systematic control chest X-ray
      detected this complication. The position of the metallic fragment was determined
      by chest CT scan and bronchial fibroscopy between the inferior right lobar
      bronches and artery confirming bronchial perforation. Rigid bronchoscopy with
      direct visualisation enabled extraction of the foreign body without
      complications.

PMID- 9181040
TI  - [Acquired pulmonary vein stenosis after surgery of complex partial anomalous
      pulmonary venous drainage in an adult. Diagnostic value of transesophageal
      echocardiography].
AB  - Surgical correction of partial anomalous pulmonary venous drainage is difficult
      and may be complicated by acquired postoperative stenosis at the site of
      reimplantation of the pulmonary veins in the left atrium. Diagnosis should be
      made quickly because of the very poor prognosis due to acute pulmonary
      hypertension. The case described by the authors underlines the value of
      multiplane transesophageal echocardiography with two-dimensional and Doppler
      analysis for rapid and accurate diagnosis of this complication.

PMID- 9181042
TI  - [Apropos of the new classification of cardiomyopathies].

PMID- 9181041
TI  - [Salmonella enteritidis pericarditis. Apropos of a case and review of the
      literature].
AB  - The authors report a case of Salmonella enteritidis pericarditis. The diagnosis
      was based on bacteriological analyses (blood and effusion cultures and
      pericardial biopsy). The microbiology of bacterial pericarditis is reviewed
      underlying the exceptionally rare finding of a non typhi Salmonella in this
      condition.

PMID- 9181043
TI  - Apoptosis: an identical central or collateral mechanism in the development,
      function and death of neurons.
AB  - The author shows that the previously known and recently re-described and
      explained process called apoptosis, or program cell death, applies not only to
      the morphologic and functional development of the embryo and the organism at any
      age, but as well to the induction and/or promotion of many major diseases. The
      death of cells which do not disappear mitotically being replaced by two daughter
      cells, the neurons, serves as an example of the extremely important role of
      apoptosis in the mechanisms of neuro-psychiatric diseases, which merits to create
      as much research interest as mitosis has generated.

PMID- 9181044
TI  - Alzheimer's disease in twins.
AB  - Besides familial Alzheimer's disease (AD), the genetic susceptibility has also
      been found in sporadic cases of AD, mostly related to the apolipoprotein E
      polymorphism. The penetrance of AD is determined by age and probably by
      environmental exposure. Gene-environment interaction of a disease can be examined
      through studies of twins. The relative roles of genetic and environmental
      influences can be estimated by comparing the concordance rates between
      monozygotic (MZ) and dizygotic (DZ) twins. Genetic models can be used to specify
      contributions both from genetic as well as shared and unique environmental
      effects. The role of environmental factors can be investigated in the co-twin
      control study, either by comparing environmental exposure in MZ twins discordant
      for a disease or by comparing MZ twins discordant for an exposure suspected of
      causing a particular disease. The sampling of twin pairs AD can be carried out
      using voluntary recruitment, linkage of twin and hospital discharge registries or
      screening of twin registry population. Potential sources of biases in sampling
      are discussed. The majority of the published twin studies on AD are case reports
      or based on selected materials. In MZ pairs, the concordance rates for AD have
      varied between 31% and 83%. Only one co-twin control study in twins discordant
      for AD has been published. Published twin studies on AD are briefly reviewed.

PMID- 9181045
TI  - Amyloid precursor protein, copper and Alzheimer's disease.
AB  - Although a consensus that Alzheimer's disease (AD) is a single disease has not
      yet been reached, the involvement of the amyloid precursor protein (APP) and beta
      A4 (A beta) in the pathologic changes advances our understanding of the
      underlying molecular alterations. Increasing evidence implicates oxidative stress
      in the neurodegenerative process of AD. This hypothesis is based on the toxicity
      of beta A4 in cell cultures, and the findings that aggregation of beta A4 can be
      induced by metal-catalyzed oxidation and that free oxygen radicals might be
      involved in APP metabolism. Another neurological disorder, familial amyotrophic
      lateral sclerosis (FALS), supports our view that AD and FALS might be linked
      through a common mechanism. In FALS, SOD-Cu(I) complexes are affected by hydrogen
      peroxide and free radicals are produced. In AD, the reduction of Cu(II) to Cu(I)
      by APP involves an electron-transfer reaction and could also lead to a production
      of hydroxyl radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I) complexes
      may contribute to neurodegeneration in AD.

PMID- 9181046
TI  - Dementia: current developments.
AB  - This is a short review of the current developments taking place in the field of
      the dementias. This branch of medicine is growing apace with fresh research
      findings being published continually in respect to etiology, risk and protective
      factors, clinical typology and treatment effects. At the same time we know
      remarkably little about the natural history of cognitive decline and in effect,
      normal aging. There is clearly a vital need for longitudinal studies. Also, new
      hypotheses are needed to explain the critical memory defect in dementia. In fact,
      better treatment of the memory defect, and the associated behavioral problems
      found in dementia is urgently needed and even demended by an increasingly more
      sophisticated public.

PMID- 9181047
TI  - Bromocriptine has little direct effect on murine lymphocytes, the
      immunomodulatory effect being mediated by the suppression of prolactin secretion.
AB  - We investigated whether the immunosuppressive effect of bromocriptine in mice is
      due to its direct effect on lymphocyte functions or through inhibition of
      prolactin secretion. Incubation of mouse Babl/c splenic lymphocytes with
      bromocriptine in vitro at a concentration of around 0.5 to 1 microgram/mL causes
      an inhibition of antigen- or mitogen-induced proliferation. However,
      bromocriptine in vitro has no effect on lymphokine production (gamma-interferon
      and interleukin-2), expression of interleukin-2 receptor or lymphocyte cytotoxic
      function. Furthermore, treatment of Babl/c mice with bromocriptine inhibits the
      mixed lymphocyte reaction and mitogen stimulation, as well as primary and
      secondary antibody production. However, we postulated that the inhibition of ex
      vivo functional activity could not account for a direct cytostatic or cytotoxic
      effect of bromocriptine. This is supported by the in vitro data, which shows that
      bromocriptine has no effect on proliferating P-815 mastocytoma tumor cells.
      Finally, (NZB/NZW) F1 mice spontaneously develop a disease similar to systemic
      lupus erythematosus. In both non-autoimmune Babl/c mice and (NZB/NZW) F1 lupus
      mice, the serum level of bromocriptine achieved by a treatment with 5 mg/kg on
      average is 2-6 ng/mL. On the one hand, this dose is sufficient to significantly
      alter the ex vivo functional tests in Babl/c mice and to show a beneficial effect
      in the in vivo model of female lupus-mice. On the other hand, the lowest
      concentration which could have an inhibitory effect on antigen- and mitogen
      induced proliferation in vitro is 200 ng/mL, ie 50 times more than that required
      in vivo to obtain significant reductions of proteinurea, glomerular membrane
      proliferation and immune deposits in lupus-mice. The serum levels of gamma
      interferon and interleukin-2 are reduced in lupus-mice when compared with Babl/c
      mice. The treatment with bromocriptine does not influence these parameters. In
      conclusion, our data demonstrate that the major immunosuppressive activity of
      bromocriptine is probably dependent on its hypoprolactinemic effect.

PMID- 9181048
TI  - Elevated serum ferritin level in acute myocardial infarction.
AB  - Serum ferritin level was determined in 20 patients with acute myocardial
      infarction (AMI) during the first 10 days post infarction. Starting on the second
      day, a gradual increase in serum ferritin level was detected, reaching a maximum
      of four times the initial level on the sixth day after the infarction. In
      addition, a significant increase in ferritin content was found in the peripheral
      blood monocytes on the fifth day after the event. The control group comprised six
      patients suffering from chest pains not due to AMI. In all of them the serum
      ferritin level was found to be within normal limits. Peripheral blood monocytes
      derived from healthy individuals incubated with hydrocortisone, showed a
      significant enhancement of their ferritin content, a finding suggesting that
      these cells activated by steroids during stress could be a source of the
      increased serum ferritin level following AMI. It is concluded that measurement of
      serum ferritin may be used as a complementary tool for confirming the diagnosis
      of AMI.

PMID- 9181049
TI  - Anticonvulsant and neurotoxicological properties of 4-amino-N-(2
      ethylphenyl)benzamide, a potent ameltolide analogue.
AB  - A well documented study on the anticonvulsant properties of 4-amino-N-(2
      ethylphenyl)benzamide (4-AEPB) is here provided. Initial screening in mice dosed
      intraperitoneally and rats dosed orally indicated that 4-AEPB is active against
      maximal electroshock-induced seizures (MES), but does not protect animals against
      subcutaneous pentylenetetrazole (sc Ptz)-induced seizures. Quantitative
      evaluation of anti-MES activity and neurotoxicity of 4-AEPB given
      intraperitoneally to mice provided ED50 and TD50 values amounting to 28.6 and
      96.3 mumol/kg respectively, resulting in a protective index (PI = TD50/ED50)
      equal to 3.36. Further quantitative evaluation in rats dosed orally indicated
      that the respective ED50 and TD50 values for 4-AEPB were 29.8 and more than 1,530
      mumol/kg, resulting in a very high PI value of over 51. Comparison anticonvulsant
      properties and neurotoxicity of 4-AEPB with those previously reported in the
      literature for two 4-aminobenzamide derivatives, 4-amino-N-(2,6
      dimethylphenyl)benzamide (or ameltolide, an antiepileptic drug prototype
      developed by Eli Lilly), and phenytoin, underlines the value of 4-AEPB for future
      pharmacological development. In this perspective, an additional favorable element
      is represented by the ability of 4-AEPB to increase the seizure threshold in the
      intravenous Ptz seizure threshold test in mice dosed intraperitoneally. Molecular
      modeling studies show that the translocation of one carbon unit in the
      isomerization of the 2,6-dimethylphenyl moiety of ameltolide to the 2-ethylphenyl
      counterpart succeeds in maintaining the conformational low energy presentation
      adopted by ameltolide, providing clues as to why the 4-AEPB here described is an
      anticonvulsant agent derived from the 4-aminobenzamide pharmacophore platform as
      potent as ameltolide.

PMID- 9181050
TI  - Extracellular matrix remodeling as a regulator of stromal-epithelial interactions
      during mammary gland development, involution and carcinogenesis.
AB  - An intact basement membrane is essential for the proper function, differentiation
      and morphology of many epithelial cells. The disruption or remodeling of the
      basement membrane occurs during normal development as well as in the disease
      state. Stromelysin-1 (SL-1), a member of the matrix metalloproteinase (MMP)
      family, was one of the first proteinases found to be associated with cancer. In
      this review we describe the role of MMPs in normal mammary gland involution. To
      examine the importance of basement membrane during development in vivo, we
      altered the MMP and tissue inhibitor of metalloproteinases (TIMP) balance in
      mammary gland. Inhibition of MMP synthesis by glucocorticoids or implants or
      transgenic overexpression of TIMP-1 delays matrix degradation and the involution
      process after weaning. The mammary glands from transgenic mice that
      inappropriately express autoactivating isoforms of SL-1 are both functionally and
      morphologically altered throughout development. Transgenic mammary glands have
      supernumerary branches, and show precocious development of alveoli that express
      beta-casein expression and undergo unscheduled apoptosis during pregnancy. This
      is accompanied by progressive development of an altered stroma, which resembles
      that of a wound site or a tumor, and becomes fibrotic after postweaning
      involution, and by development of neoplasias. These data suggest that MMPs and
      disruption of the basement membrane may play key roles in branching morphogenesis
      of mammary gland, apoptosis, and stromal fibrosis as well as in induction and
      progression of breast cancer. These observations suggest that SL-1 and other MMPs
      may be useful targets for therapeutic intervention in cancer.

PMID- 9181051
TI  - Experimental models of invasion and metastasis; can they provide reliable answers
      for the role of proteases in cancer?
AB  - This paper discusses the feasibility of extrapolating to human cancer results
      obtained concerning the role of proteases in experimental models of invasion and
      metastasis. It is customary to view metastasis as a series of individual steps,
      which must be completed in sequence for the process to be successful. The role of
      proteases in this process is usually studied by testing the blocking effects of
      various inhibitors on tumor cell invasion of extracellular matrices (ECM), or in
      assays of "experimental metastasis" (tail vein injections). The tests of
      invasion, which utilize established tumor cell lines, provide an account of the
      type of proteases that potentially may be produced by cancer cells, but, as
      indicated by recent evidence, they do not reflect the much more restricted
      repertoire of proteases detected by in situ techniques in human cancer cells. It
      is much more difficult to find in the progression of human cancer the counterpart
      to the widely used tail vein injection, which purports to test "late" stages of
      metastasis, since intravasation is most likely a slow, selective process and not
      a massive flux of a huge number of cells injected under substantial pressure
      resulting in non-physiological responses. As a rule, therefore, once it is
      established that an isolated cancer cell can produce a protease, or degrade and
      invade ECM, the question is whether this process actually occurs according to a
      model most reflective of the disease studied (such as orthotopic models) and
      whether this activity is actually present in cancer tissue sections.

PMID- 9181052
TI  - Human breast carcinoma slice cultures retain retinoic acid sensitivity.
AB  - We have shown earlier that surgical human breast cancer tissue can be maintained
      in culture as in culture as intact tissue slices (organ culture). Because tumor
      organ culture ostensibly preserves the interacting network of tumor cells,
      stromal fibroblasts, endothelial cells and extracellular matrix, it represents a
      rather complex culture system. Such a system may be especially useful in
      preclinical trials, where the objective is to make extrapolations to the even
      more complex in vivo situation. A classical therapeutic target in breast cancer
      is the estrogen receptor, and we showed earlier that human breast cancer slices
      retain expression of this receptor in culture. Retinoic acid, the active form of
      vitamin A, is also an important (negative) growth regulator in breast cancer. In
      the present communication, we used in situ hybridization to monitor the
      expression of retinoic acid receptors in tumor slices cultured for 4 days. We
      show that both members of the all-trans retinoic acid and 9-cis retinoic acid
      receptor family (RAR and RXR, respectively) are expressed. Moreover, RNase
      protection analysis showed that expression of the cellular retinoic acid-binding
      protein type II gene, a known retinoic acid target gene, is upregulated by
      treatment with 1 microM all-trans retinoic acid for 2 days. These findings attest
      to the feasibility of using tumor organ cultures as a preclinical model for the
      evaluation of synthetic vitamin A derivatives (retinoids).

PMID- 9181053
TI  - Matrix metalloproteinases and lung injury.
AB  - The dynamic equilibrium of extracellular matrix (ECM) under different
      physiological conditions is a consequence of the balance between the regulation
      of synthesis and degradation of ECM components. Matrix metalloproteinases (MMPs),
      a family of structurally related zinc-dependent endopeptidases, are the
      physiological mediators of matrix remodeling. The expression and activity of
      these enzymes are highly regulated at several intra- and extracellular levels, so
      that in vivo enzymatic activity is the final result of a complex series of events
      including gene expression, zymogen activation, matrix binding, and enzymatic
      inhibition. MMPs are expressed at low levels in normal adult tissues, and their
      upregulation appears to play an important role in the development of a number of
      pathological processes. In acute lung injury, a disorder characterized by a
      severe disruption of the gas exchange alveolo-capillary structures, the
      upregulation of interstitial collagenase and gelatinases A and B strongly
      suggests that MMPs contribute to acute lung damage by facilitating the migration
      of inflammatory cells, as well as to the disruption of basement membrane
      components and extracellular matrix remodeling.

PMID- 9181054
TI  - Pathogenic mechanisms in the development of diffuse pulmonary fibrosis.
AB  - Diffuse pulmonary fibrosis is characterized by abnormal proliferation of
      mesenchymal cells, specifically fibroblasts and myofibroblasts, and by the
      accumulation of excessive amounts of matrix proteins, mainly collagens. The
      development of this pathological process is preceded by an inflammatory response,
      often dominated by macrophages and lymphocytes, which is mediated by the local
      release of chemoattractant factors, acting coordinately with an upregulation of
      cell-surface adhesion molecules. A subsequent persisting fibroproliferative
      reaction, in both interstitial and intraalveolar spaces, with progressive
      collagen accumulation distorts the lung architecture irreversibly. Excessive
      collagen deposition is the result of an imbalance in the collagen turnover rates
      characterized by a transient increase in collagen synthesis and a decrease in
      collagen degradation. Fibrosis is considered otherwise to be the final common
      pathway of a variety of lung disorders, and in this context, the diagnosis of
      pulmonary fibrosis implies the recognition of an advanced stage in the evolution
      of a complex process of abnormal repair.

PMID- 9181055
TI  - Ha-ras oncogene transformation abolishes retinoic acid-induced reduction of
      intracellular fibronectin.
AB  - All-trans-retinoic acid (RA) is a master regulator of cell differentiation and in
      this process it greatly influences cell adhesion and the elaboration of the
      extracellular matrix. Therefore, we were interested in the effect of RA on the
      biosynthesis of fibronectin (FN). RA reduced the level of intracellular FN in a
      time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3
      cells transformed by an activated Ha-ras oncogene. Since the steady-state level
      of FN transcripts did not change after treatment of the cells with RA for various
      times or concentrations, RA probably acts at the translational level. In NIH-3T3
      cells, RA had distinct effects on different receptors, from decreasing retinoic
      acid receptor (RAR)alpha to increasing RAR beta expression to no effect on RAR
      gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene
      downmodulated RAR expression and also abolished responsiveness to RA. A variety
      of approaches permitted the following conclusions: 1) RA-dependent FN
      downmodulation is mediated by RARs, 2) retinoid X receptors (RXRs) mediate the
      observed reduction of RAR alpha by RA, and 3) the blockade of RA responsiveness
      by Ha-ras-transfected cells cannot be overcome by overexpression of RAR alpha.
      These studies have identified fibronectin and RAR alpha as RA targets in
      fibroblast cells and have shown that oncogenic transformation renders the cells
      resistant to RA action.

PMID- 9181056
TI  - Polyomavirus-induced malignant transformation: comparative analysis of wild type
      and mutant middle T-overexpressing cell lines.
AB  - Polyomavirus, a DNA tumor virus, expresses three viral oncoproteins (large,
      middle and small T antigens), causes malignant transformation in cell culture and
      induces multiple tumors in vivo. The middle T (MT) antigen seems to play an
      essential role in transformation and tumorigenicity. The observation that MT
      overexpressing cell lines are able to grow in the absence of PDGF (platelet
      derived growth factor) led several laboratories to study the mechanism underlying
      MT-induced growth deregulation and the signal transduction pathway used by this
      viral oncoprotein. A number of cellular proteins were shown to be common to both
      the normal PDGF mitogenic pathway and the MT transforming pathway. The expression
      of some PDGF primary response genes (fos, jun, myc, JE, KC) was shown to be
      rendered constitutive by MT overexpression. Using MT mutants, important domains
      for binding and activation of cytoplasmic proteins were mapped. Wild type and
      mutant MT cell lines are used in our laboratory to analyze the expression and
      activity of the PDGF early response genes during cell transformation and
      correlate them with activation of specific cytoplasmic proteins. In addition to
      abrogating the PDGF requirement for growth, activation of cellular proteins
      caused by MT results in cell lines that have an altered morphology and are able
      to form colonies in agarose. These changes may be due to alterations in connexin
      43 and other cell surface proteins.

PMID- 9181057
TI  - Laminin-binding proteins in EJ-ras-transformed fibroblasts.
AB  - Malignant transformation is accompanied by changes in cell-matrix interactions.
      Upon transfection with EJ-ras oncogene, transformed fibroblasts acquired a
      migratory phenotype towards laminin-1. The increase in integrin expression was
      responsible for the migratory activity of transformed fibroblasts. In addtion
      alpha 6 beta 1 integrins, both galectin-3 and an unidentified laminin-binding
      polypeptide had their expression pattern altered upon transformation. Here, we
      review these two classes of laminin-binding proteins and their possible roles in
      cell-laminin interactions.

PMID- 9181058
TI  - Peptides in cell adhesion: powerful tools for the study of integrin-ligand
      interactions.
AB  - Many of the cell adhesion receptors recognize simple sequences that can be
      reproduced as synthetic peptides. This circumstance has led to a widespread use
      of peptides as modulators of cell adhesion. Peptides capable of binding to cell
      adhesion receptors, such as the integrins, can be used as mediators of cell
      attachment to a surface by coating the surface with the peptide. Peptides bound
      to a solid phase can also be used to isolate adhesion receptors by affinity
      chromatography. Alternatively, the peptides can be used to inhibit cell
      attachment to the natural ligands of the adhesion receptors. In either mode,
      adhesion peptides have proven to be highly useful probes in cell adhesion
      research and they also show promise as a new class of therapeutics. The purpose
      of this article is to review some of the properties and uses of adhesion
      peptides.

PMID- 9181059
TI  - The role of the extracellular matrix in neoplastic glial invasion of the nervous
      system.
AB  - Intrinsic tumours of the central nervous system (CNS) are generally derived from
      the glial cells: the astrocytes, oligodendrocytes and ependymal cells. Although
      such tumours rarely metastasize to distant organs, they show a marked propensity
      for local invasion of the surrounding nervous tissue. Sub-populations of
      neoplastic glia may migrate several millimetres away from main tumour mass into
      the contiguous CNS parenchyma, resulting in poor demarcation of the tumour. These
      migratory, so-called "guerrilla" cells give rise to recurrent tumours following
      surgical debulking and adjuvant radio- and chemo-therapeutic intervention. As in
      other organs, tumour cell invasion is, in part, facilitated by interaction with
      the extracellular matrix (ECM); however, apart from the vascular basal lamina and
      the glia limitans externa, the CNS lacks a well-defined ECM. Invading neoplastic
      cells must, therefore, provide their own ECM, a process which may be stimulated
      by such agents as gangliosides or growth factors. Glioma cell-derived laminin and
      hyaluronic acid may provide the most important substrates for invasion, cell
      adhesion to these substrates being achieved largely through integrin receptors
      (the function of which may be determined by interaction with cell surface
      gangliosides) and CD44, respectively. Modulation of these ECM components is
      facilitated by a variety of proteinases including the matrix metalloproteinases
      and hyaluronidase, the activity of which is also thought to stimulate
      angiogenesis. Interference with the mechanisms which promote glioma cell adhesive
      properties may provide suitable targets for novel anti-invasive therapies. These
      might include ECM components, growth factors, gangliosides, integrin receptors
      and proteases and their inhibitors.

PMID- 9181060
TI  - Recruitment of brain macrophages: roles of cytokines and extracellular matrix
      proteins produced by glial or neuronal cells.
AB  - Brain macrophages are a subpopulation of microglial cells which occur in the
      developing or in the injured CNS. These cells actively contribute to CNS tissue
      remodeling by acting on neuronal and macroglial lineages. Recruitment of brain
      macrophages is promoted by transformation of resting microglial phenotypes,
      infiltration of the tissue by exogenous macrophage precursors and local
      proliferation of phagocytes. These events are regulated by extracellular signals
      produced by glial cells or neurons. Studies based on in vitro cell cultures or
      experimental tissue lesions suggest that the infiltration of phagocytes involves
      intracerebral production of chemotactic factors acting on monocytes such as
      chemokines or extracellular matrix proteins. Proliferation of brain macrophages
      in stimulated by colony-stimulating factors which seem to be primarily secreted
      by glial cells.

PMID- 9181061
TI  - The extracellular matrix of the midline and non-midline midbrain glia:
      correlations with neurite growth-supporting abilities.
AB  - The central nervous system (CNS) midline plays an important role in growth and
      guidance of axons. At the midline, a multiplicity of cell types establish
      boundaries that control the navigation of crossed and uncrossed axonal fibers.
      The extracellular matrix (ECM) molecules of the resident neuroepithelial or
      committed neuronal or glial cells could be involved in the control of axon growth
      and axon guidance. This review reports the recent advances in the study of the
      structure and functional role of the ECM at the midline locus of the CNS. In vivo
      and in vitro approaches are considered to provide new clues in the understanding
      of processes involved in the cellular decisions of the CNS midline.

PMID- 9181062
TI  - Type VI collagen in the cardiac valves and connective tissue septa during heart
      development.
AB  - A variety of extracellular matrix (ECM) proteins have been shown to be present in
      the embryonic heart during the morphogenesis of the valves and membranous septa.
      It is not known if any specific ECM protein is required for the normal
      morphogenesis of these tissues, but this is of great interest since there is a
      high incidence of congenital malformations which affect valvular and septal
      tissues. Interestingly, the alpha 1 and alpha 2 genes of type VI collagen are
      located within the region of human chromosome 21 thought to be involved in the
      congenital heart defect phenotype associated with trisomy 21 (Down's syndrome).
      In this study we examined the distribution and investigated the function of type
      VI collagen in the cardiac valves and septa of chicken and mouse embryos during
      various stages of development. Immunohistochemical and in situ hybridization
      studies revealed a pattern of cardiac expression of type VI collagen which is
      present from the earliest stages of valve and septum development through the
      neonatal period. Results from an in vitro bioassay suggest that type VI collagen
      may play a role in the formation and migration of specific cells in the forming
      valves and septa. These data support molecular genetic studies which have
      indicated that type VI collagen is involved in the heart defect phenotype seen in
      trisomy 21.

PMID- 9181063
TI  - The role of the collagenous and elastic system fibers in modulating
      bronchoconstriction.
AB  - The distribution and conformational changes of the fibers of the collagenous and
      elastic systems in guinea pig airways after a contractile agonist challenge are
      described. We observed a distinct pattern of behavior within the mucosal fibers
      during bronchoconstriction. Part of the fibers of the two systems tend to follow
      the epithelial invaginations towards the airway lumen, while the remaining ones
      seem to be attached to the internal smooth muscle. These layers of fibers in the
      mucosa are interconnected to one another and to the adventitial network by
      slender fibers. We suggest that the configuration and behavior of these fibers
      during bronchoconstriction may contribute to airway reopening after the
      contractile stimulus has ceased. The possible role of this mechanism in the
      pathophysiology of human asthma is discussed.

PMID- 9181064
TI  - The role of collagen in hematopoiesis.
AB  - Several types of collagen, including types I, III, IV, V and VI, are produced by
      bone marrow stromal cells. Current information indicates that changes in collagen
      production result in profound alterations in the capacity of hematopoietic
      precursors to proliferate and differentiate. Although not definitively
      established, collagen molecules may be involved in the establishment and
      conformation of the stroma-associated extracellular matrix and/or in adhesive
      interactions with progenitor cells. The dynamic role of collagen in hematopoiesis
      is indicated by the observation that collagen production and processing are
      regulated by several factors such as glucocorticoids, cytokines, collagenases and
      collagenase-inhibitory proteins.

PMID- 9181065
TI  - Laminin/VLA-6 interactions and T cell function.
AB  - A growing number of investigators consider extracellular matrix (ECM) proteins to
      be determinant factors in lymphocyte positioning and activation. One major ECM
      component is laminin, which is constitutively expressed in the thymus as well as
      in thymus-dependent areas of peripheral lymphoid organs. In the thymus, laminin
      is produced by epithelial and dendritic cells, and appears to mediate
      interactions with thymocytes through specific laminin receptors, in particular
      the integrin VLA-6. This receptor is also expressed by peripheral T cells, and is
      apparently involved in effector T cell migration and activation. We showed that
      CD4+ T lymphocytes from chronic chagasic mice exhibited an increase in the
      absolute and relative number of cells with high VLA-6 expression. Additionally,
      it is likely that VLA-6/laminin interactions are required for the development of
      the CD4+T cell-dependent anti-myocardial autoreactive process that occurs in
      these animals. Lastly, laminin can bind to some cytokines, a fact that may
      represent an additional mechanism by which this extracellular matrix component
      modulates the behavior of T lymphocytes. Taken together, the present data
      strongly indicate that interactions involving laminin and VLA-6 are functionally
      linked to relevant events in T cell physiology, comprising entrance of pro
      thymocytes into the thymus, intrathymic T cell migration and differentiation, as
      well as the functioning of mature T lymphocytes, including effector cells.

PMID- 9181067
TI  - Unique sulfated polysaccharides from ascidians (Chordata, Tunicata).
AB  - Unique sulfated polysaccharides have been identified in ascidian tissues. A high
      molecular-weight sulfated L-galactan consisting mainly of alpha-L-galactopyranose
      glycosidically linked through positions 1-->4, and sulfated at carbon 3 is
      present in the tunic of all species studied. Methylation, periodate oxidation, as
      well as 1H and 13C NMR analysis revealed that despite their homogeneous chemical
      composition, these L-galactans differ in type of glycosidic linkage, number of
      branches, and in the extent and position of sulfation. These L-galactans are
      synthesized by epidermal cells that epimerize D-glucose, possibly from a
      trehalose precursor, into L-galactose. In addition, a dermatan sulfate composed
      of a backbone of repeating [4-alpha-L-IdoA-1-->3-beta-D-GalNAc-1]n units similar
      to mammalian dermatan sulfate, but differing in the extent and position of
      sulfation has been isolated from the body of the ascidian, Ascidia nigra.
      Degradation of the ascidian dermatan with specific glycosidases and sulfatases,
      together with 1H and 13C NMR data, indicated that the disaccharide units are
      sulfated at the 2-position of alpha-L-induronate residues and at the 6-position
      of the N-acetyl-beta-D-galactosamine units. In contrast to mammalian dermatan
      sulfate, the ascidian molecule has no discenrible anticoagulant activity, as
      measured by the APTT assay, and has a low ability to potentiate heparin cofactor
      II. These data suggest that the 4-O-sulfation of N-acetyl-beta-D-galactosamine
      residues is essential for the anticoagulant activity of dermatan sulfate
      polymers.

PMID- 9181066
TI  - Synchronized order of appearance of hyaluronic acid (or acidic galactan) -->
      chondroitin C-6 sulfate --> chondroitin C-4/C-6 sulfate, heparan sulfate,
      dermatan sulfate --> heparin during morphogenesis, differentiation and
      development.
AB  - The synthesis of glycosaminoglycans and acidic polysaccharides during embryonic
      and fetal development in mammals and molluscs is briefly reviewed. A sequential
      order of appearance of each of the acidic polysaccharides was observed,
      coinciding with the major processes of the ontogeny. In mammals, hyaluronic acid
      is the first glycosaminoglycan synthesized at the beginning of morphogenesis.
      This glycosaminoglycan is then replaced by chondroitin 6-sulfate during the
      migration of the mesenchymal cells. Heparan sulfate, dermatan sulfate and
      chondroitin 4-sulfate are synthesized only during cell differentiation. The
      synthesis of heparin, on the other hand, is confined to mast cells in a few
      tissues and is a late event in the differentiation process. The same general
      pattern is also observed in molluscs except that hyaluronic acid is replaced by
      an acidic galactan in the morphogenetic process. The activity of the degrading
      enzymes responsible for the disappearance of hyaluronic acid, chondroitin sulfate
      and the acidic galactan in each phase of embryonic development is also reviewed.

PMID- 9181068
TI  - Detection of post-translational sulfation of alpha-5 beta-1 integrin and its role
      in integrin-fibronectin binding.
AB  - Fibronectins are glycoproteins of the extracellular matrix composed of two 220
      kDa polypeptide chains named A and B bound by two disulfide bridges. Both chains
      when digested with proteolytic enzymes give rise to six different domains named I
      to VI that are involved in the ligand properties of this molecule. Fibronectins
      bind fibrin, collagen, glycosaminoglycan residues and several integrins. In this
      study, using metabolic radiolabeling of alpha 5 beta 1 integrin with sodium
      sulfate, an immunoprecipitation reaction, inhibition of sulfate incorporation and
      a fibronectin-binding assay, we were able to detect this integrin as a sulfated
      molecule and this sulfation appears to regulate the integrin-fibronectin binding.

PMID- 9181069
TI  - Undersulfation of glycosaminoglycans reduces the proliferation of a leukemia cell
      line in vitro.
AB  - Leukemia represents the clonal expansion of an individual cell lineage of the
      hematopoietic system at a specific point of its maturation and development. This
      dysregulated expansion of cells is often accompanied by altered adherence to the
      bone marrow microenvironment and abnormalities in endogenous cytokine production
      by neoplastic cells. Proteoglycans (PGs) synthesized by neoplastic cells may
      interact with extracellular matrix (ECM) molecules and/or locally produced
      cytokines. It is believed that these events may be mediated by the
      glycosaminoglycan (GAG) moiety of PGs such as heparan or chondroitin sulfate, and
      depends on its charge. The strength of GAG-cytokine binding may be determined by
      the extent of sulfation of the GAG chains. The synthesis, metabolism and
      biological role of PGs in hematopoietic malignancies have not been clearly
      defined. In order to study how alterations of GAGs in leukemic cells may alter
      cellular behavior, we treated the murine myeloid leukemic cell line WeHi-3B with
      sodium chlorate. This drug reduces the sulfation of GAGs, since chlorate is a
      potent inhibitor of sulfate adenylyltransferase. The undersulfated GAGs produced
      by WeHi-3B cells were not efficient in controlling the mitotic rate of the cells,
      since a decrease in cell proliferation was observed in vitro. These data suggest
      that the complexes formed by GAGs with ECM components and/or cytokines may have
      an important role in the induction of leukemic cell proliferation. It is possible
      that the stimulatory activity elicited by this binding may be dependent upon the
      organization of these complexes.

PMID- 9181070
TI  - Is there a relationship between the state of aggregation of small proteoglycans
      and the biomechanical properties of tissues?
AB  - The small proteoglycans fibromodulin and decorin may play an important role in
      regulating collagen fibrillogenesis and interactions with growth factors. Here,
      we describe the presence of these proteoglycans in cartilage submitted to
      different biomechanical forces. Fibromodulin from chicken and bovine articular
      cartilage was shown to self-associate. The different states of fibromodulin
      aggregation due to disulfide bonding demonstrable in different regions of the
      same joint suggest that the presence of different biomechanical forces results in
      the differential expression of small proteoglycans. A 250-kDa complex found in
      chicken tibiotarsal cartilage, which migrates as a 59-kDa component in SDS-PAGE
      under reducing conditions, and which was recognized by anti-fibromodulin
      antibodies, was not demonstrable in tarsometatarsal cartilage where a different
      fibromodulin complex has been recently demonstrated. Biglycan and decorin were
      not expressed in the same way in different regions of the bovine knee joint,
      suggesting that there is a relationship between the expression of small
      proteoglycans and the different biomechanical properties of a tissue.

PMID- 9181071
TI  - Cellular adhesion to laminin involves a chondroitin sulfate proteoglycan.
AB  - Cell-extracellular matrix interactions are intimately involved in the regulation
      of many cellular processes such as embryonic development or tumor cell growth and
      metastasis. In our previous work we were able to detect a 90/100-kDa laminin
      binding chondroitin sulfate proteoglycan. A search for this molecule in different
      cell lines showed that it is only found in cells that adhere to laminin.

PMID- 9181072
TI  - An evaluation of immunology in Brazil (1981-1993).

PMID- 9181073
TI  - Aquaporins and water transfer across epithelial barriers.
AB  - The cloning and molecular characterization of water channels, generically called
      aquaporins, have marked a pivotal point in our understanding of water movements
      across epithelial barriers. Nevertheless, the mechanisms underlying water
      transfer across these barriers at the molecular and cellular level are not yet
      clarified. We analyze here the role of the different driving forces moving water
      across epithelia and the biophysical properties of the water channels. We will
      also review the recently cloned epithelial members of the aquaporin family,
      including their expression and distribution in different tissues.

PMID- 9181074
TI  - Effects of cadmium on Euglena gracilis membrane lipids.
AB  - The toxic effects of cadmium (2 micrograms/ml) on membrane lipids and growth of
      Euglena gracilis were studied using autotrophic (AUTO), heterotrophic (DARK) and
      mixotrophic (LIGHT) cells. Cadmium caused inhibition of cellular proliferation
      (IC50 1.2 micrograms/ml) and morphological alterations which were most pronounced
      in chloroplasts. The chlorophyll content of LIGHT cadmium-treated cells was
      reduced 42.5%. Cadmium also caused an increase in protein and total lipid content
      per cell in all three cell types. Among the membrane lipids, cholesterol content
      was lower in cadmium-treated cells cultivated under illumination (AUTO: 0.40 +/-
      0.02 vs 0.64 +/- 0.08 and LIGHT: 0.40 +/- 0.09 vs 0.53 +/- 0.01 microgram/10(5)
      cells). There were no changes in total phospholipid content, although cardiolipin
      content was altered in all three cell types, and in mixotrophic cells there was
      an increase in phosphatidylglycerol, a phospholipid typically found in
      chloroplasts. These results suggest that cadmium has an overall toxic effect on
      Euglena gracilis and that part of the effect can be ascribed to defects in the
      structure of chloroplasts and mitochondrial membranes.

PMID- 9181075
TI  - Characterization and regulation of glycine transport in Fusarium oxysporum var.
      lini.
AB  - Glycine was transported in Fusarium oxysporum cells, grown on glycine as the sole
      source of carbon and nitrogen, by a facilitated diffusion transport system with a
      half-saturation constant (Ks) of 11 mM and a maximum velocity (Vmax) of 1.2 mM (g
      dry weight)-1 h-1 at pH 5.0 and 26 degrees C. Under conditions of nitrogen
      starvation, the same system was present together with a high-affinity one (Ks) of
      about 47 microM and Vmax of about 60 microM (g dry weight)-1 h-1). The low
      affinity system was more specific than the high-affinity system. Cells grown on
      gelatine showed the same behavior. In cells grown on glucose-gelatine medium, the
      low-affinity system was poorly expressed even after carbon and nitrogen
      starvation. Moreover, addition of glucose to cells grown on glycine and
      resuspended in mineral medium caused an increase of the glycine transport
      probably due to a boost in protein synthesis. This stimulation did not affect the
      Ks of the low-affinity system. These results demonstrate that, as is the case for
      other eukaryotic systems, F. oxysporum glycine transport is under control of
      nitrogen sources but its regulation by carbon sources appears to be more complex.

PMID- 9181076
TI  - Characterization and potential uses of rabbit polyclonal antibodies against human
      plasma lecithin-cholesterol acyltransferase.
AB  - Familial and secondary deficiency of plasma lecithin-cholesterol acyltransferase
      (LCAT) produce circulating lipoprotein particles with gross structural and
      compositional abnormalities; these have adverse effects on a variety of cellular
      functions. Factors affecting hepatic synthesis and secretion of this plasma
      enzyme are largely unknown but, potentially, some of them can be investigated
      with monospecific antibodies. In the present study, enzymically active LCAT was
      purified 40,000-fold from human plasma and then used to raise polyclonal
      antibodies in New Zealand White rabbits. Addition of this antiserum (1
      microliter) to human plasma (25 microlitres) completely inhibited LCAT activity,
      although it was less effective against plasma from other species. The antibodies
      appeared to be monospecific to plasma LCAT. They gave a single precipitin arc by
      crossed immunoelectrophoresis, while immunodiffusion established that there was
      no cross-reactivity with several apolipoproteins or with serum albumin. Moreover,
      the antiserum was successfully used to detect LCAT in normal human plasma by
      Laurell rocket immunoelectrophoresis. By contrast, Western blotting of plasma
      proteins using whole LCAT antiserum was largely unsuccessful because of high
      background staining, although this could be substantially reduced by use of an
      IgG fraction. However, the whole antiserum readily immunoprecipitated LCAT
      secreted into the culture medium of HepG2 cells, a human hepatoblastoma cell
      line, pre-labelled with [35S]methionine, the [35S]-labelled LCAT appearing as a
      narrow 65-kDa protein band by electrophoresis and fluorography. We conclude that
      polyclonal antibodies may be an important tool to investigate the characteristics
      and underlying mechanisms of secondary LCAT deficiencies, including those
      associated with hepatic cirrhosis and schistosomiasis.

PMID- 9181077
TI  - Diffuse adherence, ST-I enterotoxin and CFA/IV colonization factor are encoded by
      the same plasmid in the Escherichia coli O29:H21 strain.
AB  - Escherichia coli O29:H21 is a human enterotoxigenic serotype that produces heat
      stable (ST-I) enterotoxin, adheres diffusely to HeLa cells, and presents
      colonization factor antigen IV (CFA/IV) composed of CS5CS6 surface antigens. In
      one strain studied the genes for diffuse adherence and CFA/IV (CS5CS6) production
      were found to be present in the same plasmid encoding ST-I. The virulence plasmid
      (Ent) presented two unrelated basic replicons homologous to repFIC and repW.
      Gene(s) encoding diffuse adherence did not share homology with the probe for
      F1845 fimbrial adhesin which is responsible for this phenotype in other E. coli
      strains. Ent plasmids containing genes for diffuse adherence have not been
      described previously.

PMID- 9181078
TI  - Purification, physicochemical characterization and biological properties of a
      lectin from Erythrina velutina forma aurantiaca seeds.
AB  - A lectin was purified from seeds of Erythrina velutina forma aurantiaca by
      affinity chromatography on cross-linked guar gum. The lectin is a potent
      agglutinin for human (minimal concentration of protein able to cause visible
      agglutination of a 2% erythrocyte suspension varying from 1 to 4 micrograms/ml),
      rabbit (4 micrograms/ml) and chicken erythrocytes (8 micrograms/ml) but presented
      low activity against cow (250 micrograms/ml) or sheep (333 micrograms/ml) blood
      cells. Hemagglutination of human O+ erythrocytes was inhibited by D-lactose (0.2
      mM) > D-galactose (0.8 mM) > D-raffinose (2.1 mM). At pH 7.5, chromatography on a
      Superose 12 HR 10/30 column showed that the lectin was primarily a dimer (56.0
      kDa) composed of two identical subunits (31.6 kDa each). A small amount of a
      tetrameric form was also apparently present. The lectin is a glycoprotein (7.3%
      carbohydrate), has a pI of 4.5, contains high levels of acidic (Asp and Glu, 64.2
      and 51.6 residues/mol, respectively) and hydroxy amino acids (Ser and Thr, 42.9
      and 38.5 residues/mol, respectively) but relatively low amounts of sulfur amino
      acids (Cys and Met, 1.0 and 5.0 residues/mol, respectively) and has an N-terminal
      sequence of Val-Glu-Thr-Ile/Leu-Pro-Phe-Ser. Its hemagglutinating activity was
      abolished by heating at 70 degrees C for 10 min. The activation energy (delta G')
      required for denaturation measured by loss of hemagglutination activity was 24.87
      kcal/mol. In rats, the purified lectin (100 micrograms) induced neutrophil
      migration into the peritoneal cavity (3.7 +/- 0.6 x 10(6) neutrophils/ml) or into
      the air pouch (2.75 +/- 0.25 x 10(6) neutrophils/ml), 8 and 10 times greater than
      the negative control, respectively.

PMID- 9181079
TI  - Uptake of Z-Tyr[125I]-AlaCHN2, an irreversible cysteine proteinase inhibitor, by
      lesion amastigotes, axenic amastigotes and promastigotes of Leishmania mexicana.
AB  - Radioiodinated N-benzyloxycarbonyl-tyrosyl-alanyl diazomethane (Z-Tyr[125I]
      AlaCHN2) was previously shown to selectively label two (28 and 31 kDa) Leishmania
      mexicana cysteine proteinases common to both the promastigote and the amastigote
      stages. Here we have confirmed the specificity of the compound towards two
      similar enzymes of axenic L. mexicana amastigotes and demonstrated that lesion
      amastigotes, axenic amastigotes and stationary promastigotes internalized the
      125I-labeled inhibitor at different rates. Uptake of Z-Tyr[125I]-AlaCHN2 by the
      parasites, which was not significantly modified by changing the medium pH, was
      clearly correlated with the binding of the compound to the 28- and 31-kDa
      cysteine proteinases, as judged by the specificity of enzyme labeling in gelatin
      gels and the recovery of 75% or more parasite-associated radioactivity in TCA
      insoluble fractions. For all three developmental stages, uptake markedly
      increased with time and linearly up to 60 min, but throughout the period
      examined, radiolabel accumulation occurred more efficiently in amastigotes. By 5
      h, when values were near or at saturation, radioactivity (in cpm/microgram of
      total protein) associated with lesion amastigotes was 1.8- and 2.9-times that
      recovered from axenic amastigotes and stationary promastigotes, respectively.
      Pulse-chase experiments, in which cysteine proteinases were fully blocked with Z
      Phe-AlaCHN2 prior to the pulse with Z-Tyr[125I]-AlaCHN2, showed that labeling of
      the amastigote enzymes could be partially restored, whereas labeling of
      promastigote proteinases could not, after a 5-h chase period in inhibitor-free
      medium.

PMID- 9181080
TI  - Endotoxin-induced enteric hypomotility in jaundiced loops in vitro.
AB  - Biliary obstruction may be accompanied by systemic endotoxemia due to increased
      growth of enteric microbiota and failure of hepatic clearance mechanisms. This
      endotoxemia is related to increased postoperative morbidity and mortality. An
      increased growth of the aerobic flora has been demonstrated experimentally in the
      presence of biliary obstruction, and in previous studies we observed intestinal
      hypomotility of jaundiced loops in vitro. To determine the ileal motor response
      in the presence of jaundice caused by biliary obstruction and in the presence of
      endotoxemia, an in vitro study was carried out on ileal segments from 10 female
      Holtzman rats, 2-3 months old, weighing 200 to 300 g, divided into two groups (N
      = 5); A, washed loops of jaundiced rats, and B, washed loops of jaundiced rats to
      which endotoxin was added. On the seventh postoperative day, we evaluated the
      effect of exogenous endotoxin (E. coli 0111:B4, Sigma) on the motor response to
      acetylcholine of distal ileal segments isolated from both animal groups. A 4-cm
      ileal segment, located 10 cm from the ileal papilla, was removed and studied in
      an organ chamber in order to assess dose-response curves to acetylcholine. There
      was an increase in threshold dose in jaundiced loops with intraluminally injected
      endotoxin when compared with the loops without intraluminal endotoxin (291 +/-
      188 vs 8.5 +/- 6.7 microM, P < 0.05). The maximum contraction was reduced in
      jaundiced loops with intraluminal endotoxin in relation to control loops (5.3 +/-
      1.7 vs 18.7 +/- 4.8 mm, P < 0.05), and pD2 was also reduced in jaundiced loops
      with intraluminal endotoxin in relation to control loops (2.4 +/- 0.6 vs 3.7 +/-
      0.5, P < 0.05). There was no statistical difference between jaundiced loops with
      and without intraluminal endotoxin when the maximal contraction doses were
      compared (86 +/- 66 vs 48 +/- 22 mM, P > 0.05). These results demonstrate that
      intraluminal endotoxin depressed enteric motility in jaundiced rats.

PMID- 9181081
TI  - Fetal hemoglobin in patients with chronic renal disease.
AB  - To investigate-whether hemoglobin (Hb) synthesis is affected by different
      treatment protocols used for end-stage renal disease, we analyzed the
      electrophoretic pattern of hemoglobin in 136 adult patients with chronic renal
      failure. Forty-seven patients were not in a dialysis program (ND), 29 individuals
      were on continuous ambulatory peritoneal dialysis (CAPD), 33 patients were on
      hemodialysis (HD), and 27 subjects had received a kidney transplant (KT). We
      found 3.6% hemoglobin C, 1.4% hemoglobin S and 3.6% B-thalassemia minor as
      reported in other studies of Brazilian patients. In addition, we found increased
      fetal hemoglobin (Hb F) levels in 7.4% of the patients which contrasts with the
      reported 0.01% prevalence rate of hereditary persistence of Hb F in Brazil. Seven
      out of ten patients with elevated Hb F belonged to either the CAPD or the KT
      group. We postulate that stress erythropoiesis is probably the mechanism
      responsible for the Hb F increase in these patients. However, properly designed
      clinical studies are still necessary to clarify these questions.

PMID- 9181082
TI  - Detection of living adult Wuchereria bancrofti in a patient with tropical
      pulmonary eosinophilia.
AB  - Tropical pulmonary eosinophilia (TPE) is a relatively unusual and diagnostically
      challenging manifestation of infection with Wuchereria bancrofti. The
      pathogenesis of TPE remains unclear, although immune hyperresponsiveness to the
      microfilarial stage of the parasite is thought to play an essential role.
      Microfilariae are almost never detected in the peripheral blood of persons with
      TPE and living adult worms have not been reported. Thus, no parasitologic marker
      has existed with which to assess the effectiveness of antifilarial treatment. In
      1986, a 74-year old man from Olinda, Pernambuco, Brazil, developed classic signs
      and symptoms of filarial TPE. Within 48 h after beginning treatment with
      diethylcarbamazine (DEC), the drug of choice for TPE, his symptoms dramatically
      improved. He remained symptom-free until June 1994, when he again developed signs
      and symptoms of TPE. To visualize the adult worm and monitor the macrofilaricidal
      effectiveness of DEC treatment, ultrasound examinations of the scrotal area were
      performed before, during, and for 6 months after treatment. These examinations
      revealed diffuse dilatation of the lymphatic vessels of the spermatic cord and
      movements characteristic of living adult W. bancrofti known as the "filaria dance
      sign". Although the patient responded clinically to treatment, no change was
      noted in the filaria dance sign throughout the observation period. Visualization
      of adult W. bancrofti by ultrasound can be used to monitor the parasitologic
      effectiveness of treatment for TPE and to explore the relationship between death
      of the adult worm and recurrence of symptoms.

PMID- 9181083
TI  - Fusion of Leishmania amazonensis parasitophorous vacuoles with phagosomes
      containing zymosan particles: cinemicrographic and ultrastructural observations.
AB  - Studies on fixed preparations have shown that vacuoles containing zymosan (Z)
      particles internalized by infected macrophages can selectively fuse with the
      large parasitophorous vacuoles (PVs) that shelter Leishmania amazonensis. To
      examine the kinetics of vacuolar fusion in individual cells, particles were
      followed by time-lapse cinemicrography from their uptake to their entry in a PV.
      Newly formed Z-containing vacuoles moved centripetally and, if they contacted a
      PV, the two vacuoles remained closely apposed for variable, often extended,
      periods of time before they eventually fused. Transmission electron microscopy
      confirmed that the cytoplasm separating the partner vacuoles could be reduced to
      a very thin layer. Initiation of fusion was indicated by reduced refractility of
      the boundary between Z vacuoles and target PVs. Within a few minutes the PV
      enlarged and encompassed the Z particles, which remained immobile throughout. The
      interval between phagocytosis and fusion, 50 +/- 7.4 min (N = 17; range, 4 to 108
      min), suggests that most but not all Z vacuoles underwent significant maturation
      by the time of fusion. Some particles were transferred singly, others entered PVs
      in groups of 2 or more, and additional clustered transfers to the same vacuole
      were also observed. These observations provide a baseline for studies of the
      biochemical mechanisms and the pharmacological control of the fusion of
      Leishmania PVs, and for the comparison of the fusion behavior of the PVs with
      that of other phagocytically derived vacuoles.

PMID- 9181084
TI  - Effect of pancreas transplantation on the prevention of nephropathy in alloxan
      induced diabetic rats.
AB  - We studied the effects of pancreas transplantation on kidney lesions of rats with
      alloxan-induced diabetes. Ninety inbred male Lewis rats were randomly assigned to
      3 experimental groups: group NC included 30 non-diabetic control rats, group DC
      included 30 alloxan-induced diabetic control rats, and group PT included 30
      alloxan-induced diabetic rats that received pancreas transplants from normal
      donor Lewis rats. Each group was further divided into 3 subgroups of 10 rats
      which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical
      and laboratory parameters during these periods were documented. The kidneys of 5
      rats in each subgroup were studied and 50 glomeruli and tubules from each kidney
      were analyzed by light microscopy by two different investigators in a double
      blind study. There was progressive glomerular basement membrane thickening
      (GBMT), mesangial enlargement (ME), and Bowman's capsule thickening (BCT) in
      kidneys of rats in the 3 experimental groups during follow-up. These alterations
      were significantly higher in DC rats (GBMT: 1.99 +/- 0.31; ME: 2.00 +/- 0.33;
      BCT: 1.88 +/- 0.27) when compared to NC (GBMT: 1.54 +/- 0.30; ME: 1.56 +/- 0.47;
      BCT: 1.36 +/- 0.35) and PT rats (GBMT: 1.49 +/- 0.29; ME: 1.57 +/- 0.36; BCT:
      1.35 +/- 0.28) at 6 months (P < 0.01). The extent of GBMT, ME, and BCT observed
      in DC rats at 1 and 3 months was not significantly different from NC and PT rats.
      The amount of kidney lesions in PT rats was similar to that of NC rats and lower
      than those of DC rats at 6 months (P < 0.01). In addition, Armanni-Ebstein
      lesions of the tubules (AE) and tubular lumen protein (PRO) observed in DC rats
      were not present in NC or PT rats. We conclude that pancreas transplantation in
      alloxan-induced diabetic rats prevents the development of kidney lesions
      beginning at 6 months after transplantation.

PMID- 9181085
TI  - A comparative study of the anorectic and behavioral effects of fenproporex on
      male and female rats.
AB  - The anorectic and behavioral effects of fenproporex (Fenp, 10 mg/kg, ip) and
      methamphetamine (Met, 2.5 mg/kg, ip), a prototypical example of an amphetamine
      like drug, were studied in male and female Wistar rats (5 and 3 months of age,
      respectively, at the beginning of the experiments) after acute (immediately after
      a single dose) or chronic treatment (after 60 days of administration). For the
      evaluation of the experimental parameters six groups of eight rats each were
      utilized for food intake and stereotyped behavior and six groups of nine rats
      each for body weight and motor activity. Similar anorectic effects (decreased
      food intake in grams: saline (Sal): 12.8 +/- 2.5, Met: 4.7 +/- 4.0, and Fenp: 4.4
      +/- 20; decreased weight gain: Sal: 38 +/- 10, Met: 25 +/- 1.0, and Fenp: 27 +/-
      3.0) were induced by both drugs in male rats. Female rats, however, required
      larger doses (20 mg/kg Fenp and 5.0 mg/kg Met) for a complete blockade of food
      intake. The behavioral tests were carried out 30, 60, 120, 180 and 300 min after
      drug administration and on day 1 and day 60 immediately after the treatment, for
      stereotypy and motor activity, respectively (male rats: Met: 3.8 +/- 0.3, Fenp:
      6.0 +/- 0.9, and female rats: Met: 15.4 +/- 1.9, Fenp: 9.7 +/- 1.3). Though
      stereotyped behavior such as sniffing, continuous licking, and false bites was
      observed in all animals, this was more evident and prolonged in female rats. Both
      drugs also increased motor activity (male rats, acute treatment: Met: 608 +/-
      419, Fenp: 677 +/- 354; chronic treatment: Met: 701 +/- 423, Fenp: 908 +/- 479;
      female rats, acute treatment: Met: 817 +/- 350, Fenp: 1177 +/- 282; chronic
      treatment: Met: 623 +/- 274, Fenp: 1511 +/- 573) with female rats once again
      showing greater sensitivity both after acute and chronic treatment. Our data
      indicate that fenproporex, like methamphetamine, has a stimulating effect on the
      central nervous system, indicating an action on the dopaminergic systems. These
      data further suggest that its therapeutic use as an appetite moderator should be
      prescribed with caution, especially to women, since, at least in the species
      studied, the female organism seems to show higher susceptibility to the central
      effects of this substance.

PMID- 9181086
TI  - Pinealectomy attenuates the effect of restraint on plus maze exploration in rats.
AB  - To investigate a possible stress modulation role of the pineal gland, male Wistar
      albino rats (200-250 g) were submitted to pinealectomy and divided into four
      groups one week after surgery: i) sham-operated unrestrained animals (N = 14);
      ii) pinealectomized unrestrained animals (N = 22); iii) sham-operated animals
      submitted to 2 h of restraint (N = 52); iv) pinealectomized animals submitted to
      2 h of restraint (N = 56). Twenty-four hours later the animals were tested in the
      elevated plus maze for 5 min. Pinealectomized rats submitted to restraint
      explored the open arms of the maze to a greater extent than sham-operated
      restrained rats (mean percent of open arm entries = 26.4 +/- 2.3 vs 18.0 +/- 2.1,
      mean percent of time spent in the open arms = 11.8 +/- 2.1 vs 6.8 +/- 1.2).
      Pinealectomized animals not submitted to restraint showed no difference in maze
      exploration when compared to sham-operated rats (mean percent of open arm entries
      = 29.3 +/- 3.8 vs 31.1 +/- 5.8, mean percent of time spent in the open arms = 8.8
      +/- 1.8 vs 12.5 +/- 2.2). The results, therefore, suggest that the pineal gland
      may play a modulatory role in the behavioral consequences of stress.

PMID- 9181087
TI  - Transient expression of an atypical D1-like dopamine receptor system during avian
      retina differentiation.
AB  - Intact cultured retina cells from chick embryos at stage E9C5 (cultures initiated
      with retinae from 9-day old embryos followed by 5 days in culture), preincubated
      with 2 nM unlabelled SCH 23390 (R(+)-7- chloro-8-hydroxy-3-methyl-1-phenyl
      2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) for 20 to 60 min at 37 degrees
      C and then washed 5 to 25 times (approximately 1.5 min/wash) with 2 ml SCH 23390
      free medium, responded to dopamine with cAMP accumulation that corresponded to 30
      50% of the dopamine-promoted cAMP accumulation observed in untreated cells or in
      cells exposed to the inactive isomer of SCH 23390. Therefore, 50 to 70% of the
      dopamine response of SCH 23390-pretreated cells was inhibited after extensive
      washings of the cultures. At E9C12 the fraction of the dopamine response that
      remained inhibited by SCH 23390 after the washings declined to 30% of the control
      cultures or the cultures exposed to the SCH 23390 enantiomer. Cultures at stage
      E9C5 treated with SCH 23390 followed by extensive washings as above and then used
      for measuring the number of [3H]-SCH 23390 specific binding sites revealed that
      60% of the sites did not interact with the tritiated compound when compared to
      untreated cultures or to cultures preincubated with the inactive isomer of SCH
      23390. When E9C12 cultures were subjected to the same experimental protocol less
      than 10% of D1-like sites did not interact with [3H]-SCH 23390 after the cells
      had been exposed to the unlabelled compound. Dissociated cells prepared from
      intact retinae obtained from 12-13-day old embryos also displayed a subpopulation
      of D1-like sites that interacted irreversibly with SCH 23390 in a stereospecific
      way. These sites corresponded to 25% of the total number of D1-like sites present
      in the retina at this developmental stage. In retina cells obtained from one-day
      old posthatched chicks these sites were no longer detected. These data show that
      cultured retina cells as well as cells obtained from retina developing in ovo
      display two populations of D1-like receptors. One interacts irreversibly with SCH
      23390 and is present only in the undifferentiated tissue or in cells at the early
      stages of culture and the other has a lower affinity for SCH 23390 with which its
      interaction follows reversible kinetics. These sites are present throughout the
      differentiation stages studied.

PMID- 9181088
TI  - Effects of losartan on neuroleptic-induced catalepsy in mice.
AB  - Neuroleptic-induced catalepsy remains a useful method to study central
      dopaminergic function in rodents. Evidence obtained in several studies indicates
      that this phenomenon can be modified by cholinergic, histaminergic and
      serotonergic manipulation. Angiotensin II is a central neurotransmitter acting
      through AT1 and AT2 receptors. There are few data on the effect of
      angiotensinergic drugs on dopaminergic transmission. We investigated the effect
      of losartan, a nonpeptide antagonist of central and peripheral AT1 receptors, on
      neuroleptic-induced catalepsy. Adult male albino mice, 26-35 g, were used.
      Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min
      intervals by means of a bar test. Losartan (10 or 100 ng/kg) or saline (control;
      0.13 ml) was injected intraperitoneally 20 min before H, with each animal (7 per
      group) being used only once. Losartan (10 and 100 ng/kg) significantly (P < 0.05)
      potentiated the cataleptic effect of H in comparison to the control group (e.g.
      264 +/- 26 and 299 +/- 68 sec, respectively, vs 89 +/- 24 sec for the control
      group, 90 min after H). No differences were demonstrable 120, 150 or 180 min
      after H. Considering the high selectivity and the pharmacokinetic properties of
      losartan, these data suggest that central angiotensin AT1 receptors play a role
      in neuroleptic-induced catalepsy. However, further studies are necessary to
      confirm this hypothesis and to clarify the mechanism(s) involved in this process.

PMID- 9181089
TI  - Histamine-potentiating activity in rat anaphylactic pleural fluid: role of
      serotonin.
AB  - The identity of the histamine-potentiating activity detected in the rat
      anaphylactic pleural washing was investigated. Wistar rats of both sexes,
      weighing 150-200 g, were sensitized by injecting subcutaneously (sc) a mixture of
      ovalbumin and Al(OH)3 14 days before allergen challenge. In sensitized rats,
      intrapleural (ipl) injection of ovalbumin (12 micrograms/cavity) caused an
      intense protein exudation. A single ipl administration of compound 48/80 (12
      micrograms/cavity) exhausted the resident mast cell population and turned the
      pleural cavity hyporeactive to the allergen challenge performed 5 days later.
      Allergen-induced exudation occurred in parallel to a dramatic decrease in the
      amount of cell-stored histamine (from 9.6 +/- 1.4 (N = 8) to 1.3 +/- 0.1 (N = 6)
      micrograms/cavity, P < 0.001) in the pleural fluid within 10 min. The
      anaphylactic cell-free pleural washing obtained at this time, as well as
      histamine at a concentration equivalent to that stored in pleural mast cells (10
      micrograms/cavity), did not induce pleural exudation when injected into normal
      rats. In contrast, the combined administration of histamine and anaphylactic
      pleural washing led to remarkable pleural exudation, comparable to that obtained
      with a high dose of histamine (200 micrograms/cavity) alone. It is noteworthy
      that the anaphylactic washing from compound 48/80-pretreated rats failed to
      synergize with histamine. Also, synergism was not reproduced when recipient rats
      were pretreated with methysergide (50 micrograms/cavity). Consistently, serotonin
      (5 micrograms/cavity) acted synergistically with histamine (10
      micrograms/cavity), producing a greater exudative response than observed with the
      sum of the effects of each vasoactive amine alone. The results indicate that
      serotonin accounts for the histamine-potentiating activity noted in the
      anaphylactic pleural washing, confirming that the synergistic interaction between
      these vasoactive amines plays a critical role in the rat allergic pleurisy.

PMID- 9181090
TI  - Effect of 60Co gamma radiation on Biomphalaria glabrata (Mollusca, Gastropoda)
      embryos: mortality, malformation and hatching.
AB  - A study was carried out on the radiosensitivity of Biomphalaria glabrata embryos
      submitted to doses of 5, 10, 15, 20 and 25 Gy of 60Co during the cleavage,
      blastula, gastrula, young trochophore and trochophore stages. Mortality,
      malformation and hatching were the parameters used to evaluate the damage induced
      by ionizing radiation. Estimated LD50 values (15 days) showed that the cleavage
      stage (4.3 Gy) was approximately four times more radiosensitive than the
      trochophore stage (17.0 Gy). Susceptibility to malformation induction was higher
      in the blastula, gastrula and young trochophore stages. Several types of
      morphogenetic malformations were observed, such as head malformations,
      exogastrulas, shell malformations, and embryos with everted stomodeum, with
      nonspecific malformations being the most frequent. The types of malformation
      induced by radiation probably are not radiation-specific and do not depend on the
      dose applied. The dose of 15 Gy was sufficient to greatly reduce the number of
      hatching snails regardless of the embryonic stage irradiated. We conclude that
      the effect of 60Co gamma radiation on B. glabrata embryos presented a specific
      pattern.

PMID- 9181091
TI  - Lunisolar tidal waves, geomagnetic activity and epilepsy in the light of
      multivariate coherence.
AB  - The computed daily values of lunisolar tidal waves, the observed daily values of
      Ap index, a measure of the planetary geomagnetic activity, and the daily numbers
      of patients with epileptic attacks for a group of 28 neurology patients between
      1987 and 1992 were analyzed by common, multiple and partial cross-spectral
      analysis to search for relationships between periodicities in these time series.
      Significant common and multiple coherence between them was found for rhythms with
      a period length over 3-4 months, in agreement with seasonal variations of all
      three variables. If, however, the coherence between tides and epilepsy was
      studied excluding the influence of geomagnetism, two joint infradian
      periodicities with period lengths of 8.5 and 10.7 days became significant. On the
      other hand, there were no joint rhythms for geomagnetism and epilepsy when the
      influence of tidal waves was excluded. The result suggests a more primary role of
      gravitation, compared with geomagnetism, in the multivariate process studied.

PMID- 9181092
TI  - Lunar influence on atrial fibrillation?
AB  - The most popular periodicities in biology and medicine-the circadians and
      circannuals-stem undoubtedly from the Earth's rotation and its revolution around
      the sun. The problem is how to explain the existence of circaseptan, i.e. 5-9
      day, and other infradian rhythms. They may correspond to the lunar cycles and
      their 2nd to 6th harmonics. To test such hypothesis, the calendar dates of 127
      attacks of atrial fibrillation in one male subject (M.M.) between 1980 and 1994
      were transformed into the days numbered 0-29 for the synodic, and 0-26 for tropic
      lunar cycle. The daily frequencies obtained in this way were smoothed by moving
      averages of three successive days each. Considerable fluctuations of frequencies
      of attacks during both cycles were visible by inspection of the corresponding
      graphs, called lunar plexograms. Thus, a conspicuous nadir is found under the
      full moon in the synodic cycle, and a marked peak shortly after the extreme
      southern position of the moon in the tropic cycle. Halberg's cosinor analysis
      testing the presence of the 1st to 6th harmonic of either lunar cycle rejected
      the null hypothesis at the alpha = 0.05 level for all harmonics. Accordingly, the
      occurrence of attacks was cycling with the period lengths of synodic and tropic
      lunar cycles, and with those of their 1/2-1/6 period lengths, i.e. with a cluster
      of approximately circa(di)-septan rhythms. This conclusion is supported by
      similar findings obtained earlier for various medical and biological events.

PMID- 9181093
TI  - Renal tubular sodium handling determined by lithium clearance in partially
      hepatectomized rats.
AB  - Decreased renal sodium excretion was observed 2 to 5 days after a two-thirds
      hepatectomy (Hx) in male Wistar-Hannover rats (200-300 g; N = 10 per group). This
      fall occurred after normalization of serum liver enzymes by the second day.
      Hepatocellular dysfunction was demonstrated by a pronounced and transient
      increase of about 1150% in plasma alanine aminotransferase (ALT), 500% in
      aspartate aminotransferase (AST), 250% in alkaline phosphatase (ALP) and in serum
      direct bilirubin levels, which were about six-fold higher than in sham-operated
      (SH) animals on the first and second days after hepatectomy. On the basis of the
      renal clearance of lithium in partially hepatectomized rats, there was a
      sustained decrease in fractional sodium excretion between the second (SH: 0.053
      +/- 0.008% vs Hx: 0.023 +/- 0.008%) and fifth days (SH: 0.040 +/- 0.006% vs Hx:
      0.027 +/- 0.009%) post-hepatectomy. This decrease was accompanied by a rise in
      the absolute (68 +/- 5.2 mumol min-1 100 g body weight-1) and fractional (85.2 +/
      1.4%) proximal sodium reabsorption rates compared to sham-operated rats (53 +/-
      3.5 mumol min-1 100 g body weight-1 and 80.6 +/- 1.1%), but a return to baseline
      excretion levels was observed by the tenth experimental day. These changes
      occurred in the absence of any alterations in creatinine clearance, sodium
      filtered load, hematocrit and total blood volume. Further studies are required to
      establish the mechanisms of interaction between renal tubule sodium handling and
      liver function.

PMID- 9181094
TI  - Synthesis and biological activities of some human gastrin analogs.
AB  - The synthesis of analogs of the C-terminal tridecapeptide of gastrin is
      described. These pseudopeptide analogs were obtained either by replacing the C
      terminal phenylalanine amide with 2-phenylethylalcohol or with 2
      phenylethylamine, or by replacing the peptide bond between Trp and Leu, or
      between Leu and Asp with an aminomethylene (CH2NH). The ability of these
      compounds to stimulate gastric acid secretion in anesthetized rats and to inhibit
      binding of labeled CCK-8 to isolated cells from rabbit fundic mucosa was tested.
      [desPhe13, Leu11]-HG-12-I-beta-phenylethylester 33, [desPhe13, Leu11]-HG-12-II
      beta-phenylethylester 38, [desPhe13, Leu11]-HG-12-I-beta-phenylethylamide 32, and
      [desPhe13, Leu11]-HG-12-II-beta-phenylethylamide 37 acted as gastrin receptor
      antagonists, while [Trp10-psi(CH2NH)-Leu11]-HG-13-I 31 and [Trp10-psi(CH2NH)
      Leu11]-HG-13-II 36 acted as agonists. Unexpectedly, [Leu11-psi(CH2NH)-Asp12]-HG
      13-I 30 and [Leu11-psi (CH2NH)-Asp12]-HG-13-II 35 were almost devoid of affinity
      for the gastrin receptor.

PMID- 9181095
TI  - Biolistic-mediated gene expression in guinea pigs and cattle tissue in vivo.
AB  - Foreign genes were introduced and expressed in vivo in guinea pigs and cattle
      utilizing a new hand-held device based on high-pressure helium gas to accelerate
      DNA-coated microparticles. Guinea pigs were used to evaluate the physical
      parameters to introduce and express the exogenous DNA. The best conditions were
      applied to conduct bombardments in cattle. The results showed a high frequency of
      gene expression in all the bombarded cattle. This procedure could be used to
      study the immune responses in cattle and in a wide variety of animals through
      genetic immunization.

PMID- 9181096
TI  - DNA polymorphisms of apolipoprotein B and AI-CII-AIV genes in a Brazilian
      population: a preliminary report.
AB  - Possible associations between coronary heart disease (CHD) and restriction
      fragment length polymorphisms (RFLPs) in the apo AI-CII-AIV cluster and the apo B
      gene were investigated in a Brazilian population consisting of 46 patients with
      CHD and 24 individuals without evidence of CHD. A preliminary genetic analysis of
      SstI RFLP in the apo AI-CII-AIV cluster showed a significantly higher frequency
      of the rare SstI allele (S2) in CHD patients as compared with controls. No
      significant differences were found in the frequencies of PstI RFLP in the apo AI
      CII-AIV cluster or XbaI and EcoRI RFLPs in the apo B gene between CHD patients
      and controls. Moreover, no association was seen between the RFLPs studied and
      myocardial infarction or plasma cholesterol or triglyceride levels.

PMID- 9181097
TI  - Significance of the presence of antibodies against hepatitis C virus in
      asymptomatic blood donors.
AB  - In order to determine the significance of anti-hepatitis C virus (anti-HCV)
      antibodies in blood donors, 46 consecutive asymptomatic individuals were
      recruited at the blood bank of Hospital Sao Paulo, Sao Paulo, Brazil. They were
      submitted to an interview to collect epidemiological data and to clinical
      examination and blood samples were obtained for biochemical, serological and
      virological analysis. All patients were followed for a minimum period of six
      months and those with abnormal mean alanine aminotransferase (ALT) levels were
      submitted to a liver biopsy after giving informed consent. Hepatitis C virus RNA
      (HCVRNA) was detected by the polymerase chain reaction (PCR) in 22/47 (47.8%)
      patients and this finding was associated with parenteral risk factors (P = 0.03)
      and ethanol abuse (P = 0.03). HCVRNA positivity was also associated with abnormal
      levels of ALT (P < 0.001) and gamma-glutamyl transpeptidase (gamma-GT) (P =
      0.01). Abnormal ALT levels were good marker of viremia, with 86.4% sensitivity
      and 79.2% specificity. Twenty-three patients with elevated mean ALT levels were
      submitted to a liver biopsy and histopathological changes were observed in 17 of
      them (73.9%). HCVRNA positivity was associated with severe forms of hepatic
      disease (chronic hepatitis and cirrhosis). These results indicate the need for a
      judicious evaluation of all anti-HCV-positive blood donors, including clinical
      examination, biochemical tests and liver histology when ALT is persistently
      elevated.

PMID- 9181098
TI  - Late diagnosis of chronic renal failure and the quality of life during dialysis
      treatment.
AB  - We evaluated the quality of life of 101 hemodialysis patients who had a late < or
      = 3 months before starting dialysis, N = 47) or early (> or = 6 months, N = 54)
      diagnosis of chronic renal failure. At the time of the survey patients had been
      stable on dialysis for at least 3 months and for less than 24 months; median
      duration of dialysis was 9.1 months. Quality of life was measured by the kidney
      disease questionnaire (including the intensity and duration of physical symptoms,
      fatigue, depression, relationship with others and frustration), the health and
      life satisfaction indices, functional status (Karnofsky scale), and the time
      trade-off method. Scores for the several indicators of quality of life were
      closely similar for the late and early diagnosis groups. Health satisfaction
      compared to one year prior to dialysis was slightly better for the early
      diagnosis group. For both groups, functional status was a little worse during the
      first year of dialysis than one year before its start. In the late diagnosis
      group, elderly patients and diabetics had more impairment in several dimensions
      assessed. In addition, in this group greater income was significantly correlated
      with better physical performance (r = 0.52, P < 0.001) and with health
      satisfaction (r = 0.36, P = 0.027). These findings suggest that after a median
      duration of 9 months on a dialysis program, patients with a late and early
      diagnosis of chronic renal failure have a similar performance in terms of quality
      of life parameters. Age, diabetes and income are associated with the quality of
      life of patients with a late diagnosis.

PMID- 9181099
TI  - Reduced renal sodium excretion in primary hypertensive patients after an oral
      glucose load.
AB  - This study was designed to determine urinary sodium excretion in response to an
      oral glucose load in hypertensive patients. Fifteen hypertensive patients and
      eighteen normotensive subjects were studied after an overnight fast and for 4 h
      after the ingestion of 100 g glucose. A subgroup of untreated, nonobese, primary
      hypertensive patients (five of the 15 hypertensive patients) became
      hyperinsulinemic (total area under the insulin curve [TAUC]: 33,080 +/- 3348
      microU ml(-1) 120 min-1) in response to an oral glucose load compared to
      normotensive subjects (TAUC: 3670 < 13.731 < 23,693 microU ml(-1) 120 min-1) or
      to be other subgroup of normoinsulinemic hypertensive individuals TAUC: 10,221 +/
      1615 microU ml-1 120 min-1) despite a similar serum glucose concentration in
      both groups. A significant decrease in renal sodium excretion in the entire
      hypertensive group (47.1 +/- 4.7%, P < 0.019) compared to the normotensive (20.0
      +/- 10.5%) subjects was also observed during the oral glucose tolerance test.
      Decreased renal sodium excretion was followed by a transient increase in urinary
      acid excretion. We speculate that the increase in insulin secretion may be
      responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+
      output and blood pressure in a subgroup of salt-sensitive patients with
      hypertension. New studies should be designed to identify the precise mechanisms
      involved in the interaction between hypertension, serum insulin-glucose levels
      and the magnitude of the renal tubule reabsorption abnormality.

PMID- 9181100
TI  - High incidence of anencephaly and legal rights.
AB  - This work reports a high incidence of anencephaly in a small Brazilian town
      (Santos Dumont, MG), analyzes its impact on the local population, and studies the
      legal rights of this population to protect itself from the financial burden and
      human suffering that this "epidemic" of anencephaly has caused. From 1983 through
      1992, 49% more anencephalic infants were delivered in Santos Dumont than would be
      expected from the incidence of 1:1,000 births for the general population. There
      were 10,712 births from 1983 to 1992 in a single maternity hospital, and 16 of
      these births were anencephalic infants, representing 1.49:1,000. The occurrence
      of anencephaly varied with mother's age, and an incidence of 1.9 in 1,000 infants
      was found for women ranging in age from 20 to 29 years. In addition, 4 of 5
      anencephalic infants were females, and 2 of 3 anencephalic infants were
      stillborn. No genetic or environmental factors were identified to account for
      this extremely high incidence of anencephaly in this population of about 50,000.

PMID- 9181101
TI  - Prognostic significance of BCR-ABL rearrangement in chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by
      the presence of a reciprocal translocation between chromosomes 9 and 22 in at
      least 95% of cases. At the molecular level, this translocation results in the
      activation of the ABL oncogene of chromosome 9, which becomes contiguous with the
      5' end of the BCR gene on chromosome 22. The breakpoint usually occurs between
      exons 2 and 3 (b2-a2 rearrangement), or 3 and 4 (b3-12 rearrangement) of the
      major breakpoint cluster region (M-BCR) of the BCR gene. The aim of the present
      study was to characterize the type of BCR-ABL transcript in 32 patients with CML
      using the reverse transcriptase-polymerase chain reaction (RT-PCR) and to
      determine if this type of rearrangement is related to the survival of the
      patients. Our results confirmed that RT-PCR is more sensitive than cytogenetic
      analysis for identifying the Philadelphia (Ph1) chromosome (96.9% vs 79.3%). The
      frequencies of b2-a2 and b3-a2 rearrangements were 28.1% and 65.7%, respectively.
      The survival of patients presenting the b2-a2 or the b3-a2 rearrangement was not
      significantly different (P = 0.27750). The data suggest that the type of
      transcript has no prognostic value for CML patients.

PMID- 9181102
TI  - Transmission of visceral leishmaniasis by blood transfusion in hamsters.
AB  - We have studied the transmission of visceral leishmaniasis by blood transfusion
      in the CB hamster model. Five normal CB hamsters (females, 2.5 months old)
      received a 0.1-ml blood transfusion from a donor that had been infected with
      10(7) amastigotes of Leishmania donovani 90 days prior to the blood harvest. The
      development of the disease in transfused animals was monitored by the increase in
      anti-Leishmania serum antibodies, splenomegaly, and spleen and liver parasitic
      burdens. The transfused hamsters developed all the typical signs of the disease,
      i.e., ascites, cachexia and death. The scores of anti-Leishmania antibodies
      (1.345) and the level of parasite load (spleen Leishman Donovan units of Stauber
      (LDU) = 471, liver LDU = 378) in transfuse hamsters were similar to those
      observed in hamsters experimentally infected with 10(7) amastigotes (P > 0.05,
      Student t-test). Our results demonstrate that blood transfusion is an effective
      route for transmission of visceral leishmaniasis, and we point out that adequate
      precautions should be taken at blood banks in the regions where leishmaniasis is
      endemic.

PMID- 9181103
TI  - Distinct antigenic subtypes of human beta interferon can be distinguished by
      neutralization.
AB  - Different molecular configurations of human beta interferon were titrated with
      the standard reference antiserum of the National Institutes of Health (NIH) which
      had been prepared with natural beta fibroblast interferon in order to determine
      to what extent differences in these configurations would influence the
      neutralization of the antiviral action of interferon. Neutralization tests were
      carried out in Vero cells by diluting both interferon and antiserum.
      Encephalomyocarditis virus was employed as challenge virus. The neutralization
      titer was considered to have been reached when the effect of eight units of
      interferon was reduced to one. Two natural beta interferons prepared from
      fibroblasts and from amniotic membranes gave similar high titers. However, titers
      were reduced five-fold with recombinant interferons expressed in Escherichia
      coli, which do not contain carbohydrate, one with the natural sequence and a
      mutant with a single amino acid substitution (cysteine for serine). The NIH
      antiserum did not neutralize the effect of a protein fraction from amniotic
      membranes antigenically different from the human alpha, beta or gamma interferons
      but having the biological activity of interferon. We conclude that the
      carbohydrate moieties of human beta interferons are essential for their
      recognition by the NIH antiserum and that antibodies specific for human
      recombinant beta interferon, which does not contain carbohydrate, are needed.

PMID- 9181104
TI  - Effect of fixed epimastigote forms of Trypanosoma cruzi on the hemocytes and the
      prophenoloxidase-activating system of the crayfish Pacifastacus leniusculus.
AB  - The effect of the parasite Trypanosoma cruzi on the hemocytes and the
      prophenoloxidase (proPO)-activating system of the crayfish Pacifastacus
      leniusculus was studied. Incubation of the crayfish hemocyte lysate with fixed
      epimastigote forms of the parasites (4 x 10(5) cells/ml) induced a marked
      activation of the crayfish proPO system, measured as phenoloxidase activity. The
      activation of proPO by the parasite was much stronger (7-fold) than that induced
      by beta-1, 3-glucans (1 mg/ml) which are known to be efficient elicitors of the
      proPO system. The fixed parasites promoted the spreading and degranulation of
      different populations of the crayfish hemocytes isolated by Percoll gradients,
      and were often observed to be attached to the crayfish hemocytes in rosette-like
      fashion. The attachment of the epimastigote forms of T. cruzi to the crayfish
      blood cell surface was not dependent on the adhesive 76-kDa protein released by
      the crayfish hemocytes, since the exocytotic inhibitor SITS and monospecific
      antibodies to the 76-kDa protein did not prevent parasite adhesion. The crayfish
      hemocytes apparently are able to phagocytose the fixed epimastigote forms of T.
      cruzi in vitro.

PMID- 9181106
TI  - Effect of adjuvants on the antibody response of mice to Bothrops asper
      (Terciopelo) snake venom.
AB  - The adjuvant properties of several immunostimulant molecules on the murine
      antibody response to Bothrops asper snake venom were evaluated. Mice receiving
      venom together with either sodium alginate, calcium alginate, aluminum hydroxide,
      muramyl dipeptide, killed Brucella abortus or B. abortus smooth
      lipopolysaccharide developed a similar antibody response. Despite the fact that
      in some cases animals injected with venom and Salmonella montevideo
      lipopolysaccharide developed a significantly higher antibody titer when compared
      to other experimental groups, no statistically significant differences were
      observed in most of the comparisons.

PMID- 9181105
TI  - Effect of long-term treatment with insulin and/or acarbose on glomerular basement
      membrane thickening in alloxan-diabetic rats.
AB  - Acarbose is a competitive inhibitor of the intestinal alpha-glycosidases, that
      can delay absorption of intestinal carbohydrates causing their malabsorption. In
      the present paper we studied the effects of insulin, acarbose and their
      association on glomerular basement membrane thickening in alloxan-diabetic rats.
      Twenty-five male and female Wistar rats, approximately 3 months old at the
      beginning of the experiment, were assigned randomly to each of five experimental
      groups: normal control rats, alloxan-diabetic control rats, alloxan-diabetic rats
      treated with acarbose, alloxan-diabetic rats treated with insulin, and alloxan
      diabetic rats treated with insulin plus acarbose. Alloxan was administered in a
      single i.v. dose of 442 mg/kg body weight. Insulin was given subcutaneously at
      doses of 18 to 30 IU/kg corrected daily on the basis of glycosuria and ketonuria.
      Acarbose was given mixed with rat chow in a dose of 50 mg/100 g chow. Body
      weight, water and food intake and diuresis, as well as blood and urine glucose
      were determined after 1, 3, 6, 9, and 12 months of treatment. Glomerular basement
      membrane (GBM) thickening was determined by electron microscopy at the same
      times. Clear clinical and laboratory signs of severe diabetes, with blood glucose
      levels above 200 mg/dl and urine glucose above 3000 mg/dl, were observed in all
      alloxan-diabetic control rats, in all periods of follow-up, whereas
      administration of insulin or acarbose reduced the blood glucose levels of treated
      groups. The most satisfactory control of blood and urine glucose was observed in
      animals treated with both insulin and acarbose. However, diarrhea was observed in
      diabetic rats treated with acarbose associated or not with insulin. GBM
      thickening was correlated with age in all groups. Beginning at six months after
      diabetes induction, the GBM of untreated diabetic rats was significantly thicker
      (mean +/- SEM, 4.446 +/- 0.45 mm) than that of normal rats (2.977 +/- 0.63mm).
      Both insulin and acarbose prevented GBM thickening and their combination induced
      thickening similar to the age dependent thickening observed for normal rats of
      the same age. We conclude that acarbose when combined with insulin may be a good
      option in the control of diabetes and its renal complications.

PMID- 9181107
TI  - Backup compass mechanisms in pigeon orientation with the sun in the zenith.
AB  - The sun is known to guide homing pigeons as a priority cue. The literature
      indicates that under total overcast conditions pigeons rely on a backup mechanism
      akin to the magnetic inclination compass for which there is much laboratory
      evidence in migratory birds. Total overcast conditions are not favorable for
      orientation research in the State of Sao Paulo, Brazil. The orientation of homing
      pigeons raised near the tropic of Capricorn was therefore observed around the
      time of the December solstice, when the sun culminated directly overhead, with a
      consequent interruption of the sun compass for a short time every day. In these
      experiments, carried out between 1981 and 1993, local geomagnetic field
      inclination was -25 degrees to -29 degrees 30', so that a functioning magnetic
      inclination compass should have been available to the birds. Whereas the birds
      released with sun to zenith angles between 10 degrees and 30 degrees were well
      oriented, both in the morning (99 vanishing bearings) and in the afternoon (143
      vanishing bearings), those released with the sun less than 5 degrees away from
      the zenith showed random orientation (105 vanishing bearings), with no evidence
      of an alternative magnetic compass mechanism.

PMID- 9181108
TI  - Effects of haloperidol on behavioral responses induced by electrical stimulation
      of medial prefrontal cortex.
AB  - The effects of haloperidol on circling and spying behaviors induced by electrical
      stimulation of the medial prefrontal cortex (PFC) were evaluated. Male Wistar
      rats with an electrode implanted into the left medial PFC (B: 2.5 mm A, 0.6 mm L
      and 2.7 mm V) were electrically stimulated in a sequence of ten 30-sec trains
      separated by 30-sec intervals (60 Hz) in each session, and simultaneously
      observed in the open field. The animals with circling (CI) and spying (SP)
      behaviors were treated with intraperitoneal haloperidol (HAL ip, 5 mg/kg, N = 6)
      and saline (SAL ip, N = 7) or intracortical HAL (ic, 5 micrograms, N = 6) and SAL
      (ic, N = 9), 20 min before the session of electrical stimulation. HAL ic
      significantly decreased (P < 0.05) CI (mean frequency +/- SEM: 0.5 +/- 0.16) and
      nonsignificantly decreased SP behavior (0.6 +/- 0.17) compared to SAL ic (CI: 0.9
      0.02, SP: 1 +/- 0). HAL ip full abolished these behaviors (P < 0.05) (CI: 0.02 +/
      0, SP: 1 +/- 0) compared to SAL ip (CI: 0.86 +/- 0.06, SP: 0:93 +/- 0.06). These
      results show that haloperidol, a dopaminergic antagonist and antipsychotic agent,
      interfered significantly with the expression of behaviors induced by electrical
      stimulation of the left medial PFC, suggesting that the induction of these
      behaviors may involve the dopaminergic neurotransmission.

PMID- 9181109
TI  - Histochemical characterization of NADPH-diaphorase activity in area 17 of diurnal
      and nocturnal primates and rodents.
AB  - NADPH-diaphorase (NADPH-d) activity was studied comparatively in area 17 of four
      mammalian species, two primates and two rodents. Three brain hemispheres each
      from adult capuchin-monkeys, owl-monkeys, agoutis and guinea pigs were fixed with
      aldehyde fixatives by perfusion and 200 microns sections were submitted to NADPH
      d histochemistry, using the indirect malic enzyme method. In all species studied
      the neuropil pattern of enzymes activity presented a clear layered appearance. In
      primates, histochemical staining was most intense in layer IVc, while in rodents
      the highest intensity of the neuropil reaction was in supragranular layers (II
      and III). Comparison of cell density in grey and white matter showed that the
      majority of NADPH-d-positive neurones were located in the white matter of
      primates but not of rodents. Since NADPH-d is a nitric oxide synthase the results
      are very important for comparative functional studies of neuromediators and their
      correlations with laminar and modular organization of area 17 of the mammalian
      brain.

PMID- 9181110
TI  - Morphometric analysis of intrinsic axon terminals of Cebus monkey area 17.
AB  - A morphological study of intrinsic projection in area 17 of Cebus monkey was
      conducted after iontophoretic injection of biocytin. Thirty axon terminals
      located in supragranular layers were qualitatively and quantitatively analyzed
      using 3-d automatic microscopy. Three types of axon terminals could be
      identified: Ia, Ib and II. Group I was characterized by a sparse and/or long
      distance branch pattern, while type II presented compact and localized
      arborization. Ia axon terminals formed "clusters" and "terminaux" boutons while
      Ib did not. On average, group II axon terminals tended to present straight or
      obtuse branching angles and a much more ramified pattern, and occupy a smaller
      cortical territory with shorter intermediate segments and higher density of
      synaptic potential sites than group I. The common characteristics of group I
      included innervation of larger cortical territories, longer intermediate
      segments, acute branching angles and lower synaptic density compared to group II.
      The results are compatible with the major subdivisions of neocortical neuronal
      morphology that classifies them as smooth and spine neurons. Smooth neurons may
      be related to axon terminals of group II while spine neurons may be related to
      group I.

PMID- 9181111
TI  - Circadian and ultradian rhythms of drinking behavior of albino rats maintained in
      constant darkness.
AB  - The objective of the present study was to investigate the circadian and the
      ultradian rhythms of drinking behavior in Wistar rats maintained under conditions
      of constant darkness. Six mature male rats (weighing 270-350 g) were exposed to
      light-dark 12:12-h cycles (LD 12:12, light on at 12:00 h) for 35 days and then
      switched to constant darkness (DD) conditions for at least 2 weeks. Drinking
      behavior was monitored continuously with a standard drinkometer circuit and the
      data was stored in 5-min bins. A modification of Enright's periodogram technique
      was used to evaluate the free-running drinking behavior circadian rhythm.
      Ultradian rhythms in drinking behavior were estimated by the Fast Fourier
      Transform (FFT) technique. Two of the animals (rats 4 and 6) showed no
      statistically significant circadian or ultradian rhythms and the other four
      showed free-running drinking circadian rhythm behavior shorter than 24 h (ranging
      from 23.333 to 23.967 h). Ultradian rhythms of drinking behavior of 12- and 8-h
      periods were detected in 4 (rats 1, 2, 3 and 5) and 2 (rats 1 and 5) animals,
      respectively. The relation of the compound structure of the circadian and
      ultradian rhythms is discussed demonstrating that drinking behavior is a good
      marker for studies of physiology of temporal organization.

PMID- 9181112
TI  - The effect of a low dose versus a conventional dose of hydrochlorothiazide on
      ventricular fibrillation threshold and electrolyte levels in laboratory rats.
AB  - We studied the effect of hydrochlorothiazide on metabolic and electrolyte
      parameters. In the first protocol, six groups of rats were studied to determine
      whether changes in ventricular fibrillation threshold, and serum and myocardial
      potassium occur after treatment with different doses of hydrochlorothiazide;
      three groups (N = 15) served as controls and the other three groups (N = 15) were
      given different doses of hydrochlorothiazide for a 3 month period. Two rats from
      each group were sacrificed daily. One rat heart was perfused using the
      Langendorff perfusion apparatus and the other used for myocardial potassium
      analysis. Blood was also collected for serum potassium analysis. There was no
      change in the threshold for ventricular fibrillation in groups treated with 0.04
      mg and 0.09 mg hydrochlorothiazide compared to control values. There was a
      nonsignificant decrease in serum and myocardial potassium levels in rats treated
      with 0.04 mg and 0.09 mg hydrochlorothiazide compared to control. Seven of the 15
      rats treated with 0.18 mg hydrochlorothiazide showed significantly lower
      ventricular fibrillation threshold levels and decreased serum potassium (P <
      0.02) compared to control animals. In addition, a significant decrease in
      myocardial potassium was noted (P < 0.05). In the second protocol, 8 of the 15
      rats treated with 0.18 mg hydrochlorothiazide showed reduced ventricular
      fibrillation threshold and serum potassium levels (P < 0.05). A significant
      decrease in myocardial potassium was also observed (P < 0.05). These variables
      were corrected by the intragastric administration of potassium salts. The present
      study indicates that 0.04 mg and 0.09 mg hydrochlorothiazide have no effect on
      ventricular fibrillation threshold level or on serum or myocardial potassium
      levels. There was a significant decrease in ventricular fibrillation threshold
      and serum and myocardial potassium levels in 7 of the 15 animals studied in
      protocol one and 8 of the 15 animals studied in protocol two, treated with 0.18
      mg hydrochlorothiazide and these variables were corrected by the intragastric
      administration of potassium salts.

PMID- 9181113
TI  - Antinociceptive effect of purine nucleotides.
AB  - The antinociceptive effect of purine nucleotides administered systematically (sc)
      was determined using the formalin and writhing tests in adult male albino mice.
      The mechanisms underlying nucleotide-induced antinociception were investigated by
      preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1
      mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or
      purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg;
      quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP)
      and triphosphate (ATP) caused a reduction in the number of writhes and in the
      time of licking the formalin-injected paw. Naloxone had no effect on adenosine-
      or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and
      theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and
      adenine nucleotide derivatives in both tests. P2 antagonists did not reverse
      adenine nucleotide-induced antinociception. These results suggest that
      antinociceptive effect of adenine nucleotides is mediated by adenosine.

PMID- 9181114
TI  - Effect of gamma interferon and interleukin 10 on phosphoinositol turnover by
      human neutrophils in vitro.
AB  - We evaluated the levels of inositolmono-(IP1), di(IP2), tri-(IP3) and
      tetraphosphates (IP4) in human neutrophils (N) stimulated with gamma interferon
      (IFN-gamma) (200 microliters from a pool of cell culture supernatant obtained
      from 1 x 10(7) PHA-primed peripheral blood mononuclear cells (30-60 min at 37
      degrees C, 5% CO2)) in the presence of in the absence of interleukin 10 (IL-10)
      (10 micrograms/10 microliters). The results, reported as mean +/- SEM cpm, showed
      that IFN-gamma induced a significant increase only in the IP3 level (N + medium =
      1,413 +/- 172 and N + IFN-gamma = 8,875 +/- 832). However, this activation
      mediated by IFN-gamma was blocked partially in the presence of IL-10 (N + IFN
      gamma + IL-10 = 2,430 +/- 239) (P < 0.05). Interleukin 10 alone did not induce
      significant alterations in the content of IP1 (1,203 +/- 123), IP2 (1,880 +/-
      163), IP3 (938 +/- 102) or IP4 (2,403 +/- 345) when compared to the respective
      controls in the absence of IL-10 (IP1 = 1,625 +/- 132; IP2 = 1,343 +/- 149; P3 =
      1,413 +/- 172 and IP4 = 3,281 +/- 234). We also demonstrated the inhibitory
      effect of IL-10 of chemoluminescence generation by human neutrophils during
      phagocytosis of opsonized particles (OZ). Chemoluminescence generation was
      enhanced by IFN-gamma (N = OZ = 42.8 +/- 3.9 and N + OZ + IFN-gamma = 66.5 +/-
      4.3) and this effect was reduced by IL-10 (N + OZ + IFN-gamma + IL-10 = 37.6 +/-
      5.1). These data suggest that IL-10 modulates the neutrophil response and may be
      important for the development of new treatments of inflammatory injury.

PMID- 9181115
TI  - Measurement of glomerular filtration rate using inulin prepared from Vernonia
      herbacea, a Brazilian native species.
AB  - Vernonia herbacea (Vell.) Rusby (Asteraceae) is a perennial herb native to the
      cerrado vegetation of tropical areas in Brazil, which accumulates inulin in the
      underground reserve organs. The aim of this paper was to determine whether the
      inulin extracted from V. herbacea could replace commercial inulin for the
      measurement of glomerular filtration rate (GFR). Underground organs of vegetative
      plants were collected from a preserved area of the Brazilian cerrado. The inulin
      fraction utilized was obtained by ethanol precipitation after discarding the high
      molecular mass fructans in the freeze-thawing precipitate. GFR was determined in
      male Wistar rats anesthetized with inactin (100 mg/kg), which received
      intravenously commercial inulin obtained from Dahlia sp (Sigma) or Vernonia
      herbacea inulin (30 mg/100 g) as a priming dose and 0.05 mg min-1 100 g-1 as a
      sustaining dose in isotonic saline at the rate of 0/055 ml/min. Clearance was
      determined during 3 periods, with urine collected from the bladder and blood from
      the carotid artery. There was no significant difference in the GFR measured by
      clearance in inulin from both sources even when the plasma concentration of
      inulin from V. herbacea was doubled. The mean arterial pressure did not vary
      after the application of both inulins, indicating that they do not produce
      systemic side effects. The filtered load and the excreted amount of inulin from
      V. herbacea were equal, showing that the substance is not influenced by tubular
      function. These results demonstrate that the inulin from V. herbacea can
      substitute for imported inulin for the determination of GFR and in experiments of
      kidney microperfusion as a marker of tubular water reabsorption.

PMID- 9181116
TI  - Electrophysiological properties of L-type Ca2+ currents in isolated adult mouse
      ventricular myocytes.
AB  - The whole-cell configuration of the patch-clamp technique was used to analyze the
      electrophysiological characteristics of the L-type calcium current (ICa) in
      single ventricular myocytes from hearts of adult mice. In Tyrode solution, ICa
      activated ar -30mV peaked at 0 mV, and reverted near +60 mV, the peak current
      density was -8.1 +/- 2.5 pA/pF (N = 14). In a Na(+)- and K(+)-free solution
      containing 12 microM tetrodotoxin, and 10 mM Ca2+ or Ba2+ as charge carrier, the
      current-voltage relationship and the voltage dependence of inactivation were
      shifted about 10 mV to more depolarized voltages. The maximum Ba2+ current was
      two-times greater than the maximum Ca2+ current. The voltage dependencies of
      steady-state activation and inactivation were determined within the range of -70
      to l mV and fitted with Boltzmann relations. The Ca2+ current showed half-maximal
      activation at -9.94 +/- 3.86 mV (slope factor (k) = 5.9 +/- 0.68 mV) and half
      maximal inactivation at -27.65 +/- 5.74 mV (k = 6.37 +/- 2.79 mV), while the Ba2+
      current showed half-maximal activation at -0.35 +/- 2.43 mV (k = 6.0 +/- 0.84 mV)
      and half-maximal inactivation at -20.33 +/- 2.40 mV (k = 5.36 +/- 1.10 mV). The
      time course of recovery of Ba2+ current from inactivation could be described
      using a single exponential function with a time constant of 83.37 msec. The
      overlap of activation and inactivation curves suggests the existence of an L-type
      Ca2+ window current with a maximal amplitude near -20mV.

PMID- 9181118
TI  - Expression from cardiomyocyte-specific promoter after adenovirus-mediated gene
      transfer in vitro and in vivo.
AB  - Adenoviruses are very attractive vectors for gene transfer into the cardiac
      muscle; however, their promiscuous tissue tropism, leading to an ectopic
      expression of the transgene, is a considerable practical limitation. To restrict
      expression of a reporter gene in cultured cardiomyocytes and in the heart of the
      rat, we have constructed a recombinant adenovirus (Ad-MLC2 beta gal) containing
      the beta-galactosidase gene under the control of the rat ventricle-specific
      cardiac myosin light chain 2 (MLC-2v) promoter. We show in this work that the MLC
      2v promoter inside the adenoviral genome retains its cardiac specificity in vitro
      in cultured cardiomyocytes as well as in vivo in the animal heart. Northern blot
      studies after Ad-MLC2 beta gal infection show significant transcription only in
      cells derived from the cardiac muscle and not from the skeletal muscle.
      Quantitative analysis of the beta-galactosidase activity in a number of cell
      lines also confirms this result. The level of beta-galactosidase expression in
      rat neonatal cardiomyocytes infected with Ad-MLC2 beta gal is 8% of that found
      when primary cells are infected with Ad-RSV beta gal (containing a beta
      galactosidase gene under the control of the Rous sarcoma virus promoter). The
      cardiomyocytes-specific expression is also found after injection of Ad-MLC2 beta
      gal directly into the rat myocardium, although the viral genome can be detected
      by polymerase chain reaction (PCR) in other tissues. Lack of expression after
      direct injection into liver and skeletal muscle confirms these results. The use
      of a tissue-specific promoter is a first step to restrict transgene expression to
      a particular cell type of the targeted tissue.

PMID- 9181117
TI  - Effect of aging on cortical spreading depression.
AB  - The effects of aging on spreading depression (SD) were investigated in the
      Mongolian gerbil (G; age range 1.5 to 58 months; N = 35) and in albino rat (R;
      2.5 to 24 months; N = 100). Two strains of rats were studied: Wistar (W; N = 35)
      and Sprague-Dawley (SDAW; N = 65). SDAW rats were divided into two groups: one
      group was fed a commercial lab chow diet (CD) containing 22% protein (N = 47),
      and the other was fed a 22% casein diet (CAS; N = 18). SD was elicited on the
      frontal cortical surface by 1-min application of 2% KCl and its appearance was
      recorded (ECoG and DC potential) at two points in the parieto-occipital area of
      the same hemisphere. SD propagation velocity was measured on the basis of the
      time spent for an SD "wave" to cross the distance between the two recording
      points. Within the age range studied, older animals displayed significantly lower
      SD velocities than the younger ones, independent of the species, strain or diet
      (velocity ranges, in mm/min: G, 2.22-5.99; W, 2.47-4.12; SDAW-CD, 2.32-4.42 and
      SDAW-CAS, 2.65-4.14). The correlation coefficients between age and SD velocity
      were: G. -0.78; W, -0.45; SDAW-CD, -0.68 and SDAW-CAS, -0.72 (P < 0.05 in all
      cases). As a rule, at each time point the gerbils presented higher SD velocities
      than the rats of the same age. In another set of experiments, in order to test
      the role of free radicals in SD, 7 gerbils (14-51 months old) and 13 W rats (3-24
      months old) were fed a 22% casein diet free of the antioxidant vitamins C and E
      for 4-6 weeks before the experiments. No correlation was found between age and SD
      propagation in these animals fed a diet free of vitamins C and E, although
      gerbils displayed higher SD velocities than age-matched rats (velocities: G, 3.70
      5.34; R, 3.25-4.44 mm/min; correlation coefficients: G; -0.39; W, -0/29; P >
      0.05). These data indicate that gerbils have higher SD susceptibility than rats
      of the same age, and that this susceptibility decreases with aging in both
      species. The lack of correlation between age and SD velocity in the animals fed a
      diet free of antioxidant vitamins suggests a possible role of free radicals in
      cortical SD, in accordance with evidence from other laboratories obtained in the
      isolated retina.

PMID- 9181119
TI  - Insight into cystic fibrosis by structural modelling of CFTR first nucleotide
      binding fold (NBF1).
AB  - Cystic fibrosis is a human monogenic genetic disease caused by mutations in the
      cystic fibrosis (CF) gene, which encodes a membrane protein which functions as a
      channel: the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
      The most frequent mutation, a deletion of phenylalanine F508 (delta F508), is
      located in the first nucleotide binding domain of CFTR: NBF1. This mutation leads
      to a folding defect in NBF1, responsible for an incomplete maturation of CFTR.
      The absence of CFTR at the surface of epithelial cells causes the disease.
      Determination of the three-dimensional (3D) structure of NBF1 is a key step to
      understanding the alterations induced by the mutation. In the absence of any
      experimental data, we have chosen to build a 3D model for NBF1. This model was
      built by homology modelling starting from F1-ATPase, the only protein of known 3D
      structure in the ATP binding cassette (ABC) family. This new model defines the
      central and critical position of F508, predicted in the hydrophobic core of NBF1.
      F508 indeed could be involved in hydrophobic interactions to ensure a correct
      folding pathway. Moreover, this model enables the localization of the LSGGQ
      sequence (a highly conserved sequence in the ABC family) in a loop, at the
      surface of the protein. This reinforces the hypothesis of its role for mediation
      of domain-domain interactions of functional significance for the channel
      regulation. Finally, the model also allows redefinition of the ends of NBF1
      within the CFTR sequence. These extremities are defined by the secondary
      structure elements that are involved in the NBF1 fold. They lead to
      reconsideration of the C-terminal limit which was initially defined by the end of
      exon 12.

PMID- 9181120
TI  - [In vitro gene expression of aromatase in rat testicular cells].
AB  - The ability of the male gonad to convert androgens into estrogens is well known;
      the microsomal enzymatic complex involved in this transformation is named
      aromatase and is composed of a specific cytochrome P450 aromatase (P450arom) and
      a ubiquitous reductase. Using a highly specific RT-PCR method we have measured
      the amount of P450arom mRNA in purified Leydig and Sertoli cells prepared from
      20, 40 and 70-80 day-old rats. The amount of P450arom mRNA in the Leydig cells is
      independent of age (40 x 10(-3) attomoles/micrograms of total RNA); in contrast,
      in the immature rat Sertoli cells, after 5 days of culture the amount of P450arom
      mRNA is 20-fold lower when compared to that of 20-day-old rat Sertoli cells (71 x
      10(-3) attomoles/micrograms of total RNA). Nevertheless, irrespective of the age,
      the addition of either FSH or dbcAMP for 6 h increases the level of P450arom mRNA
      in the rat Sertoli cell preparations. Therefore, we evidenced that during
      testicular maturation not only the Leydig cells but also the Sertoli cells of the
      rat have the capacity to express the gene for cytochrome P450 aromatase.

PMID- 9181121
TI  - Locomotory, ventilatory and metabolic responses of the subterranean Stenasellus
      virei (Crustacea, Isopoda) to severe hypoxia and subsequent recovery.
AB  - The locomotory and ventilatory activities and the intermediary and energy
      metabolism modifications of the hypogean aquatic isopod crustacean Stenasellus
      virei were investigated in severe hypoxia (PO2 < 0.03 kPa) and subsequent
      recovery. The aims of this study were i) to determine why the subterranean
      species displayed a greater tolerance of hypoxia than numerous other epigean
      crustaceans, ii) to confirm previous results obtained with four hypogean and
      epigean crustaceans, iii) to compare the responses to severe hypoxia in hypogean
      amphipods and isopods, and iv) to better understand the ecological problems of
      the hypogean organisms survival in subterranean habitats. S. virei responded to
      experimental long-term, severe hypoxia with classical anaerobic metabolism mainly
      characterized by a decrease in adenosine triphosphate (ATP) and phosphagen,
      utilization of glycogen and glutamate, and accumulation of lactate and alanine.
      Lactate was also largely excreted by this organism, which is unusual for
      crustaceans in general. Compared to most other epigean crustaceans, the isopod S.
      virei showed high amounts of stored glycogen and arginine phosphate. These
      differences in glycogen and phosphagen stores, and the ability to reduce
      energetic expenditures linked to locomotion and ventilation, extended the
      survival of S. virei under experimental anaerobiosis. During recovery, the isopod
      S. virei showed a higher capacity for glyconeogenesis from lactate and a faster
      and total replenishment of ATP and arginine phosphate levels than epigean
      crustaceans. Data concerning responses to hypoxia and subsequent recovery in S.
      virei are similar to those previously obtained with two other hypogean amphipods,
      except that this isopod did not synthesize succinate in anaerobiosis.

PMID- 9181123
TI  - Isolation of villous microvessels from the human placenta.
AB  - A method for isolating the microvessels of the human placental villi has been
      developed in order to culture perivascular cells. It consists of an initial
      selection of the villi by serial sieving. The villi retained by the 75 microns
      sieve were digested by collagenase-dispase. A Percoll gradient permitted the
      isolation of microvessels still surrounded by stromal fibres and cells. Another
      digestion by collagenase-dispase eliminated the contaminant elements and allowed,
      after a new Percoll gradient, microvessels with endothelium, basement membrane
      and a few perivascular cells to be obtained. Each step of the isolation of
      microvessels was monitored by light or electron microscopy. Our study confirms
      the isolation of microvessels embedded in their basement membrane and the
      preservation of endothelial and perivascular cells after digestion. This method,
      which has permitted the culture of placental endothelial cells and pericytes,
      appears of interest for studying microvascular angiogenesis and permeability.

PMID- 9181122
TI  - [Role of the conformation changement of CD4 in the HIV-cell fusion].
AB  - It is well known that the gp120-gp41 complex undergoes a conformational change
      after CD4 binding. It is likely that CD4 undergoes a conformational change as
      well. Recently, a calculation of the normal modes of the two N-terminal domains
      of CD4 has shown that a hinge-bending motion of one of these domains with respect
      to the other may occur. In the present study, results obtained previously are
      verified with two other normal mode calculations, starting from crystallographic
      structures of different origin. A scheme describing the first steps of the
      process leading to cell infection by human immunodeficiency virus (HIV) is then
      proposed. It rests upon the idea that CD4 and gp120-gp41 conformational changes
      allow for bringing the cell and virus membranes closer to each other.

PMID- 9181124
TI  - [Developmental genes].
AB  - In the present review article, we have attempted to define and class the so
      called "developmental genes". This designation applies to genes whose activity is
      involved in lineage determination, in differentiation pathways or in the modes of
      tissue or organ formation. A special emphasis has been given to genes controlling
      the body plan in the course of development. Three main subclasses of such genes
      are described: genes involved in very early development by establishing the
      anteroposterior or dorso-ventral axes of the embryo (or of the insect larva);
      segmentation genes; homeotic genes containing an homeodomain (HD) motif and
      homeotic-related genes (with a "LIM" or "PAX" motif). While classical (HD
      containing) homeotic genes were initially discovered and studied in drosophila,
      their general occurrence in many other species, particularly in vertebrates was
      soon reported. They are characterized phylogenetically speaking, by a high degree
      of sequence similarities and chromosomal organization, although their number
      appears much greater in vertebrates than in insects due to successive duplication
      and chromosomal distribution events. In vertebrates they are essentially involved
      in the development of the central nervous system. Large varieties of genes with
      "LIM" or "PAX" motifs have been reported, and many subclasses can be
      distinguished depending upon the presence or absence of distinct peptidic motifs
      within the genes under concern. The peptidic domains encoded by the LIM motifs
      include "Zn finger" containing varieties which are involved in protein-protein
      interactions. The roles of genes with a LIM motif vary according to the type of
      sub-variety (organization of the central nervous system; axonal distribution of
      peripheric nerves at distinct levels of the spinal cord, control of tissue
      differentiation, etc.). "Pax" genes include a DNA binding domain (encoded by the
      "paired" motif) with variable sequences and organization, which is sometime in
      the vicinity of an homeodomain. Generally speaking "Pax" genes behave like
      controlling elements in the development of the brain or of tissues derived from
      the neural crest.

PMID- 9181125
TI  - [Control of limb morphogenesis by the Hox genes].
AB  - Vertebrate limbs are an amazing example of successful adaptation to various
      environmental conditions. In higher vertebrates, forelimbs help to fly, swim,
      walk, dig or grasp, yet their basic structure (the sequence and spatial
      arrangement of bony elements) is always the same. This implies the existence of a
      unique developmental strategy for building a limb (a limb plan) that imposes
      early on a basic scheme, on the top of which subsequent species-specific
      customizations will occur. The description of such a universal limb plan, hence
      the idea that the genetic and developmental processes that generate this plan are
      very ancient, has been controversial for about a century. It is worth asking
      whether recent discoveries of important genes involved in these processes can
      bring novel arguments to the debate.

PMID- 9181126
TI  - [Genetic control of rhombencephalon development by Hox genes studied in bird
      embryo by the quail-chick chimera method].
AB  - The rhombencephalic neural tube is transiently segmented along the
      anteroposterior axis into 8 rhombomeres. Each rhombomere, as well as its derived
      neural crest cells, is characterized by the expression of a specific set of Hox
      genes which constitute its Hox code. This code is supposed to define the
      morphogenetic program of these cells according to their position. We took
      advantage of the quail/chick chimera system to study the regulation of Hox gene
      expression in neural tube and neural crest cells. We have therefore ectopically
      transplanted the presumptive territories of the future rhombomeres and studied
      the evolution of their Hox code. We evidence in the posterior rhombencephalon and
      the spinal cord a posteriorising signal able to induce Hox gene expression, to
      repress anterior molecular markers and to control the subsequent development of
      the neural tube. This signal is conveyed horizontally in the plane of the
      neuroepithelium and vertically from the mesoderm to the ectoderm. The
      anteroposterior identity of the neural crest cells seem independent from this
      inducer after formation of the neural fold.

PMID- 9181127
TI  - [Early stages of myogenesis as seen through the action of the myf-5 gene].
AB  - Skeletal muscles in the vertebrate body are derived from the somites, epithelial
      spheres of cells which segment from the paraxial mesoderm in a rostral-caudal
      developmental gradient on either side of the neural tube. Initially, cells in the
      somite are multipotent and their fate depends on the environmental influences
      exerted by neighbouring tissues, notably the axial structures (neural tube and
      notochord), and the dorsal ectoderm. The ventralizing influence exerted by the
      notochord and floor plate of the neural tube through the action of sonic
      hedgehog, results in the differentiation of sclerotome which will give rise to
      cartilage and bone of the vertebral column and ribs. The dorsal derivatives of
      the somite, formed from cells in the dermomyotome, are derm and skeletal muscle.
      The onset of skeletal myogenesis is characterized by expression of myogenic
      factors, notably myf-5 and MyoD, members of the superfamily of helix-loop-helix
      transcription factors. Another member of the myogenic factor family, myogenin, is
      subsequently expressed and leads to muscle cell differentiation with activation
      of the downstream muscle-specific genes. Dorsalization of the somite and
      subsequent myogenesis depends on the presence of axial structures and dorsal
      ectoderm. The Wnt family of signalling molecules are potentially implicated in
      this process. Muscle progenitor cells present in the medial part of the
      dermomyotome activate myf-5 first and explant experiments have shown that the
      axial structures lead to the activation of this myogenic factor and subsequent
      myogenesis which results in the formation of the dorsal myotome in the central
      region of the somite. This contributes to the formation of axial muscles. Muscle
      progenitor cells in the lateral part of the dermomyotome preferentially activate
      MyoD and this depends on the presence of dorsal ectoderm. These cells will form
      the ventral aspect of the myotome, and later contribute to body wall muscles, for
      example. Part of the lateral progenitor population migrates away from the somite
      to form peripheral body muscles and the muscles of the limb. In this case
      myogenic factors are not initially expressed and these migratory cells are
      characterized by the expression of the paired-box gene Pax3. In explant
      experiments lateral mesoderm retards the induction of MyoD expression by dorsal
      ectoderm; in vivo this may be important to permit cell migration prior to
      differentiation. In mice carrying mutations in both MyoD and myf-5 no skeletal
      muscle forms, whereas myogenesis can take place in the absence of either MyoD or
      myf-5. Normally, cells in which one gene is activated first, subsequently co
      express the other, so that there rapidly cease to be distinct MyoD+ or myf-5+
      populations in the embryo. In myf-5-/- mice no myotome forms initially, but MyoD
      is subsequently activated. This takes place medially, as well as laterally, under
      the influence of the more mature neural tube and notochord. By targetting the myf
      5 gene with an nlacZ reporter gene it has been possible to follow the fate of the
      early muscle progenitor cell population in which the myf-5 gene has been
      activated but no myf-5 protein is present. These beta-galactosidase positive
      cells delaminate from the dermomyotome, but instead of migrating under this
      epithelium to form the myotome, they migrate aberrantly. Some cells localize
      dorsally under the epiderm and begin to express the dermal marker, Dermo-1. Other
      muscle progenitor cells migrate ventrally into the sclerotomal compartment where
      they express an early sclerotomal marker, scleraxis. Later in the mutant mice,
      when cells from this compartment have condensed to form the cartilage of the
      ribs, beta-galactosidase positive cells are detectable within the ribs. These
      observations indicate that the early myogenic factor myf-5 is necessary to ensure
      the correct positioning of myogenic progenitor cells within the embryo. (ABSTRACT
      TRUNCATED)

PMID- 9181128
TI  - [Signalling by Notch family receptors].
AB  - From nematode to man, the transmembrane receptors of the Notch family act
      throughout embryonic and post-embryonic development to regulate the acquisition
      and/or maintenance of specific differentiative states. We will review here our
      current state of knowledge on Notch receptors structure and signalling activity.

PMID- 9181129
TI  - [Genetic control of the development by retinoic acid].
AB  - Two families of nuclear receptors for retinoic acid (RA) have been characterized.
      Members of the RAR family (types alpha, beta and gamma and their isoforms alpha
      1, alpha 2, beta 1 to beta 4, and gamma 1 and gamma 2) are activated by most
      physiologically occurring retinoids (all-trans RA, 9-cis RA, 4oxo RA and 3,4
      dihyroRA). In contrast, members of the RXR family (types alpha, beta and gamma
      and their isoforms) are activated by 9cis-RA only. In addition to the
      multiplicity of receptors, the complexity of retinoid signalling is further
      increased by the fact that, at least in vitro, RARs bind to their cognate
      response elements as heterodimers with RXRs. Moreover, RXRs can also bind, in
      vitro, to some DNA elements as homodimers, and are heterodimeric partners for
      other nuclear receptors, including TRs, VDR, PPARs and a number of orphan nuclear
      receptors. To evaluate the functions of the different RARs and RXRs types and
      isoforms, we have generated null mutant mice by targeted gene disruption in ES
      cells. As to the functions of RARs, we found that RAR alpha 1 and RAR gamma 2
      null mutant mice are apparently normal. Mice deficient in RAR alpha or RAR gamma
      (i.e., all alpha or gamma isoforms disrupted) show aspects of the post-natal
      vitamin A deficiency (VAD) syndrome which can be cured or prevented by RA,
      including post-natal lethality, poor weight gain and male sterility. RAR beta 2
      (and RAR beta) null mutants display a retrolenticular membrane which represents
      the most frequent defect of the fetal VAD syndrome. That these abnormalities were
      restricted to a small subset of the tissues normally expressing these receptors
      suggested that some degree of functional redundancy should exist in the RAR
      family. To test this hypothesis we then generated RAR double null mutants. RAR
      alpha beta, RAR alpha gamma and RAR beta gamma compound mutants exhibit all the
      malformations of the fetal VAD syndrome, thus demonstrating that RA is the
      vitamin A derivative which plays a crucial role at many different stages and in
      different structures during organogenesis. Interestingly, almost all the
      structures derived from mesenchymal neural crests cells (NCC) are affected in RAR
      compound mutants. As to the functions of RXRs, RXR gamma null mutants are viable,
      fertile and morphologically normal. In contrast, RXR alpha null fetuses display a
      thin ventricular wall and die in utero from cardiac failure. A myocardial
      hypoplasia has also been observed in some RAR compound mutants as well as in VAD
      fetuses. Thus, RXR alpha seems to act as an inhibitor of ventricular cardiocyte
      differentiation and/or as a positive regulator of their proliferation, and these
      functions might involve heterodimerization with RARs and activation by RA. RXR
      beta null mutants are viable but the males are sterile, most probably because of
      an abnormal lipid metabolism in the Sertoli cells. New abnormalities, absent in
      RXR alpha mutants, are generated in RXR alpha/RAR (alpha, beta or gamma) compound
      mutants. All these abnormalities are also seen in RAR double mutants as well as
      in VAD fetuses. In contrast, such manifestations of synergism are not observed
      between the RXR beta or RXR gamma and the RAR (alpha, beta or gamma) null
      mutations. These data strongly support the conclusion that RXR alpha/RAR
      heterodimers represent the main functional units of the RA signalling pathway
      during embryonic development. Moreover, since RXR gamma-/-/RXR beta-/-/RXR alpha
      +/-mutants are viable, a single allele of RXR alpha can perform most of the
      developmental RXR functions.

PMID- 9181130
TI  - [Role of the Krox-20 gene in the development of rhombencephalon].
AB  - In the hindbrain region of the developing CNS, anteroposterior patterning
      involves a transient segmentation process which leads to the formation of
      morphological bulges called rhombomeres. The rhombomeres constitute cell lineage
      restriction units and participate in the establishment of a metameric pattern
      which is responsible for the segmental organisation of motor and reticular
      neurons. Like Drosophila compartments, rhombomeres also constitute domains of
      specific gene expression. Genes expressed in a rhombomere-specific manner so far
      identified encode various types of putative regulatory molecules, including
      transcription factors, like Hox proteins, the zinc finger protein Krox-20 and the
      basic domain leucine-zipper protein kreisler, and receptor type molecules, like
      Sek-1, a member of the EPH family of tyrosine kinase receptors. Such genes are
      thought to play a role either in the definition of segmental territories or in
      the specification of the identity of the rhombomeres. Initial analysis of the
      function of some of these genes have indeed supported this hypothesis. This is
      the case for the Krox-20 gene. It is expressed within the developing hindbrain in
      two transverse domains which prefigure and then coincide with r3 and r5. We have
      inactivated Krox-20 by homologous recombination in ES cells and demonstrated that
      the mutation leads to the deletion of r3 and r5. The mutation introduced into the
      Krox-20 gene involved the in-frame insertion of the lacZ coding sequence. This
      allowed us to follow the late expression pattern of the gene and to identify two
      additional phenotypes, affecting myelination of the peripheral nervous system and
      endochondral ossification. The lacZ reporter also permitted a detailed analysis
      of the expression of Krox-20 in peripheral glial cells, revealing important steps
      in the control of their development. Recently we have performed a detailed
      analysis of specific neuronal populations affected by the mutation which shed new
      light on the role of Krox-20 in the segmentation and on the physiological
      consequences of its inactivation. We have also identified several new members of
      the Sek-1 family of receptor tyrosine kinases, which are also expressed in a
      rhombomere-specific manner. Finally, we have provided evidence that Krox-20 is as
      a key regulator of r3/r5-specific transcription, controlling the expression of at
      least five other regulator genes in these rhombomeres. In three cases, Hoxb-2,
      Hoxa-2 and Sek-1, we could demonstrate that Krox-20 was directly involved in the
      transcriptional activation of these genes.

PMID- 9181131
TI  - [Identification of NPDC-1, gene involved in the control of proliferation and
      differentiation of neural and glial precursors].
AB  - Most of the genes involved in the regulation of proliferation and differentiation
      of neural cells remain to be identified. With the aim of identifying such genes,
      the strategy we used was to search for cDNAs which both hybridized with helix
      loop-helix degenerated probes and corresponded to RNAs expressed preferentially
      when neural precursor cells become growth-arrested and began to differentiate.
      This led to the isolation of NPDC-1 cDNA and then of the genomic sequence. We
      observed that NPDC-1 is specially expressed in the nervous system and that the
      transfection of neural precursors with NPDC-1 cDNA results in the inhibition of
      cell proliferation. Moreover, the stable introduction of NPDC-1 into transformed
      cells downregulates cell proliferation both by increasing the generation time and
      by suppressing transformed and tumorigenic properties. We verified that these
      biological effects were reversed by NPDC-1 anti-sense oligonucleotides. Then we
      have examined the expression of NPDC-1 mRNA along mouse development and the
      interactions of the NPDC-1 protein with cell cycle regulatory proteins. The
      results showed that NPDC-1 mRNA begins to be expressed in a variety of neural
      structures, when the precursors enter their terminal differentiation. In
      addition, we have observed that NPDC-1 protein interacts with the transcription
      factor E2F-1. As a whole, the present results show that NPDC-1 down-regulates the
      proliferation of neural precursors, is able to suppress oncogenic transformation,
      is involved in the terminal differentiation of neural cells and acts probably
      through interactions with E2F-1.

PMID- 9181132
TI  - [Genetic control of hematopoiesis].
AB  - Commitment and differentiation of hematopoietic stem cells are associated with
      the progressive restriction of cellular proliferation and the progressive
      expression of a subset of genes encoding the markers of mature cells. These two
      processes are genetically regulated and, in this paper, I review the expression
      and function of the GATA family of transcription factors as an example of this
      genetic regulation. GATA cis-acting elements are found in most of the regulatory
      regions of T-lymphoid, erythrocytic and megakaryocytic restricted genes. These
      GATA motifs are recognized by the members of a family of transcriptional
      regulators: the GATA family. Three members of this family, GATA-1, 2 and 3 are
      expressed in hematopoietic cells. They are necessary for the erythrocytic and
      megakaryocytic lineages (GATA-1), for the T-lymphoid lineage (GATA-3), and for
      the proliferation of uncommitted hematopoietic precursors (GATA-2). GATA-1
      displays at least four functions: activation of the erythrocytic and
      megakaryocytic specific genes, regulation of the epsilon-->gamma globin switch
      and control of the cell cycle. These two last functions will be discussed to show
      the multiple facets of GATA-1 in the genetic regulation of hematopoiesis.

PMID- 9181133
TI  - [Cholesterol and development].
AB  - The teratogenic action of distal inhibitors of cholesterol synthesis has been
      known for some time. The induced malformations are of a particular type: they
      include holoprosencephalies. Recently these observations have solicited increased
      interest due to: 1/ the discovery in 1993 of a similar form of inhibition of
      cholesterol synthesis which is responsible for a human malformation syndrome,
      Smith-Lemli-Opitz; 2/ the demonstration of the involvement of the Sonic Hedgehog
      gene in normal development of prosencephalon and the description of the mode of
      action of the protein Shh: autoprocessing followed by "cholesterolisation".

PMID- 9181134
TI  - [Cloning of testican/SPOCK in man and mouse. Neuromuscular expression
      perspectives in pathology].
AB  - We have recently cloned a novel proteoglycan initially identified in human testis
      and hence previously called testican. A close examination of the overall protein
      structure reveals three main regions: four osteonectin/SPARC-like domains
      encompassing the amino-terminal and central part of the deduced protein, a Kazal
      like motif overlapping the third domain, and the CWCV domain in the carboxyl
      terminal end region of the protein core. We propose to call it SPOCK, the acronym
      of SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan, according to its
      specific multidomain structure. To get further insight into the function, a
      Northern blot analysis was performed in order to determine the site of expression
      in various adult tissues; a 5.2 kb transcript appeared only but strongly in mouse
      brain. The structure of the murine brain proteoglycan was determined through
      molecular cloning; human and mouse deduced proteins are highly homologous with
      95% overall amino acid identity. Murine brain serial sections hybridized with
      cDNA and immunological probes revealed identical distribution in discrete
      cerebral regions, such as CA3 hippocampal region and cerebellum. Immunoelectron
      microscopy showed the antigen selectively localized in the post-synaptic density
      of scattered pyramidal neurons and Purkinje cells. Structural analysis, a main
      expression in nervous system and preliminary assignment of the human gene in a
      critical region for neuropathologies, suggest that SPOCK may be of importance in
      neural development and neurodegenerative diseases.

PMID- 9181135
TI  - [Toxocara canis infection. 2 cases of peripheral granuloma in adults].
AB  - PURPOSE: We report two cases of toxocariasis peripheral granuloma in adults.
      METHODS: Diagnostic difficulties linked to parasite serologies, particular to
      these two cases, are presented. Serology is often poorly contributive, but PCA
      and/or vitreous study with the ELISA reaction to Toxocara canis homologous
      antigens in the endocular fluids are the most reliable means of reaching a
      diagnosis, as evidence in our two observations. In the same way, the presence of
      eosinophils and of IgE in the aqueous humor and or vitreous is of great
      importance for orienting the diagnosis. RESULTS: The treatment consisted in
      systemic steroids and granuloma cryotherapy associated with vitrectomy and for
      one case indentation due to a traction. Later, retinal membrane peel was
      performed for the same patient. No treatment with antihelminthic drugs was
      proposed. The functional and anatomic results were good in both cases (8/10-P2
      and 6/10-P2). CONCLUSION: Toxocara canis infection is based on clinical aspects.
      The ELISA technique is useful for biological diagnosis.

PMID- 9181136
TI  - [Ocular signs of primary hyperoxaluria type I].
AB  - PURPOSE: To report the results of ophthalmological examination of 14 patients
      with primary oxalosis of type I, and to appreciate the diagnostic value of these
      signs. MATERIAL AND METHODS: Fourteen patients, 7 girls and 7 boys with an
      average age of 8-35 years (3 months - 15 years). Ten patients had renal failure,
      2 died without dialysis and eight were treated with dialysis; 5 out of 8 had
      hemodialysis and the duration of this treatment varied between 3 months and 3.5
      years, 3 out of 8 had peritoneal dialysis. RESULTS: Visual acuity was 10/10 in 11
      cases and we noted a vision of 5/10 in one eye in one case. Ocular fundus
      examination was normal in 7 cases. In 5 cases, it showed numerous minute white
      round flecks at the posterior pole and near the retinal vessels which probably
      correspond to deposition of calcium oxalate crystals. In one case we found a
      diffuse retinal pigment atrophy and in another case a sectorial papillar atrophy
      without loss of vision. CONCLUSION: This flecked retinopathy can occur before
      hemodialysis or after a few months or years of hemodialysis. There is no
      correlation between duration of dialysis and ocular lesions.

PMID- 9181137
TI  - [Vitrectomy and proliferative diabetic retinopathy. Apropos of 66 eyes].
AB  - PURPOSE: We report a retrospective study about vitrectomy in diabetic patients
      and the analysis of anatomical and functional results after surgery. METHODS: We
      studied 66 eyes of 52 diabetic patients who underwent pars plana vitrectomy.
      Vitrectomy was performed for nonclearing intravitreous hemorrhage in 75% of eyes
      and for tractional macular retinal detachment in 14% of eyes. RESULTS: After
      vitrectomy for intravitreous hemorrhage, visual acuity increased in 84% of eyes
      with more than 5/10 in half the cases. After vitrectomy for tractional retinal
      detachment, visual acuity increased or became stable in only 55% of eyes. The
      major complication of surgery was recurrence of intravitreous hemorrhage. A new
      surgery was not necessary in most cases. Neovascular glaucoma, phtysis, retinal
      detachment and cataract were the other complications of surgery. CONCLUSION:
      Visual prognosis after vitrectomy performed in complicated diabetic retinopathy
      depends on the final macular function. Surgery for intravitreous hemorrhage
      without macular detachment produced in most of cases a good visual acuity. On the
      other hand, vitrectomy for tractional macular retinal detachment was followed by
      poor visual prognosis. After recurrent intravitreous hemorrhage, a new surgical
      procedure is possible with good visual results in most cases, even if several
      procedures are necessary.

PMID- 9181139
TI  - [Astigmatism caused by superior and temporal corneal incisions in cataract
      surgery].
AB  - PURPOSE: To compare induced astigmatism and postoperative astigmatism of a 4 mm
      corneal superior incision to a 4 mm temporal incision for cataract
      phacoemulsification surgery. METHODS: Sixty eyes underwent cataract surgery for
      this prospective study. Thirty had a superior corneal incision (group 1) and 30
      had a temporal incision (group 2). The incision was placed according to the pre
      operative astigmatism:temporal approach in case of against the rule astigmatism
      and superior location in case of with the rule astigmatism. The incision was
      enlarged to 4 mm just before implantation of a foldable lens. The patients had a
      pre operative and a post operative (day 1, 8, 30, 180) keratometry. Some had a
      corneal topography too. The surgically induced astigmatism was calculated using
      Naeser method. RESULTS: The incision having a relaxing effect on the meridian
      where it is placed, the surgically induced astigmatism is against the rule for a
      superior location and with the rule for a temporal location. At day 30 the mean
      surgically induced astigmatism was 0.98 diopter in group 1 and 0.58 in group 2.
      At ay 30 the postoperative astigmatism was 0.51 diopter against the rule in the
      first group and 0.13 diopter with the rule in the second group. CONCLUSION: The
      superior corneal incision rarely allows to reach a minimum postoperative
      astigmatism as with a temporal location.

PMID- 9181138
TI  - [Description of the prismation method in the rehabilitation of low visions of
      macular origin].
AB  - GOALS: This work aimed at presenting an original rehabilitation method based on
      the prismation available for patients with organic lesions of the macula. We
      report results obtained in our first series of patients. MATERIAL AND METHODS:
      The treatment was given to 14 patients, 7 women and 7 men, aged from 68 to 92
      years, with an average age of 81.64, followed in "Low Vision" consultation, and
      suffering from bilateral macular diseases. All the patients with age-related
      macular degeneration developed retinal correspondences. They all received a
      bilateral prismation over their old correction. The orientation of the prisms
      taking into account the eccentric fixations. The criteria chosen for surveillance
      were binocular subjective and objective acuity, contrast sensitivity and vision
      of colours. RESULTS: For all the patients concerned, the method led to an
      immediate subjective improvement of the visual function. Tolerance to optical
      support was improved. The patients recovered better self-sufficiency in their
      daily life. The objective binocular for VA was improved by at least one line for
      92.86% of the patients, by at least 2 lines for 42.85% and by 3 lines for 7.14%.
      The binocular contrast sensitivity was better for all the patients. Regarding the
      vision of binocular colours, the examination performance time was improved for
      all the patients. CONCLUSIONS: Prismation allows optimal use of the corresponding
      eccentric fixation areas. It appears as an interesting new therapeutic method for
      patients with macular-related low vision. It is complementary to rehabilitation
      treatment of such patients.

PMID- 9181140
TI  - [Quantitative topographic detection of keratoconus in the contralateral eye in
      clinically unilateral keratoconus. Apropos of 5 cases].
AB  - BACKGROUND: Keratoconus is generally bilateral and follows an asymmetrical
      course. The goal of this study was to evaluate efficiency of the automated
      topographic screening indices on early keratoconus by examination of the fellow
      eyes of clinically unilateral keratoconus. PATIENTS AND METHOD: We examined the
      fellow eyes of 5 cases of clinically unilateral keratoconus by videokeratography
      using TMS-1 Computed Anatomy device, which incorporates the keratoconus screening
      indices from Rabinowitz (K and I-S values) and Klyce/Maeda (KPI value and other
      quantitative induces as OSI, DSI and CSI). RESULTS: One case (number 1) had
      keratoconus detected by both Rabinowitz and Klyce/Maeda indices. Two cases
      (number 2 and 3) had normal keratoconus screening indices. Two cases (number 4
      and 5) had keratoconus detected by Rabinowitz I-S value, with a 0% KPI value.
      CONCLUSIONS: Rabinowitz indices are sensitive with a poor specificity. The
      Klyce/Maeda indices are less sensitive but more specific. Both methods may be
      useful for keratoconus detection. The results must always be analysed in relation
      to a clinical observation of both eyes and the course of the topographic changes.

PMID- 9181141
TI  - [Meibomian adenocarcinoma in its blepharo-conjunctival form. Apropos of a case].
AB  - A case of Meibomian carcinoma of the left eyelid was observed in a 53-year-old
      female patient. SHe had been previously treated for chronic unilateral
      blepharoconjunctivitis; an excisional biopsy disclosed a Meibomian carcinoma.
      First a total resection of both left eyelids was performed with plastic
      reconstructive surgery, three months later a recurrence required an orbital
      exenteration. This case underlines the interest of an early diagnosis which
      allows a more conservative treatment. The diagnosis must be kept in mind in any
      case of chronic unilateral blepharoconjunctivitis; histopathology has a key role
      in the diagnosis of Meibomian carcinoma.

PMID- 9181142
TI  - [Hamartoma of the pigment epithelium and retina. Apropos of a case].
AB  - The retinal pigment epithelium and retinal hamartoma is a rare benign tumor. We
      describe a case of combined hamartoma of the pigment epithelium and retina in an
      eight year-old-girl with strabismus and amblyopia. The fluoresceinic angiography
      and the echography allowed to exclude a malignant tumor of the retina or the
      choroid. The clinical follow-up confirmed that the lesion was stationary.
      History, pathogeny, differential diagnostics and treatment are discussed.

PMID- 9181143
TI  - [Recommendations of the ALFEDIAM (French Association for the Study of Diabetes
      and Metabolic Diseases) for the screening and surveillance of diabetic
      retinopathy].

PMID- 9181145
TI  - [Myopia and retinal detachment].

PMID- 9181144
TI  - [Role of integrins in ocular physiology and diseases].

PMID- 9181146
TI  - [Cell cycle clock and its dysregulation in bronchopulmonary cancers].
AB  - The cell cycle is the process in which two daughter cells are produced with a
      strictly identical genetic makeup to the mother cell. Several genes are
      implicated in activating (oncogenes) or inhibiting (tumor suppressor genes) the
      cycle. Abnormal gene function can contribute to development of cancer. We
      describe here the normal cell cycle, its regulation and dysregulation in
      bronchogenic cancer.

PMID- 9181147
TI  - [Evaluation of the everyday use of a metered dose aerosol triggered by inhalation
      (the "Autohaler" system)].
AB  - Although corticosteroids or beta2-agonists administered by inhalation are
      recommended as a first line treatment of asthma, standard pressurized metered
      dose inhalers are used correctly in only 3-% of cases. This study on the new
      breath-actuated inhaler Autohaler fulfils two objectives: first, to evaluate the
      respective influence of the reading of the instruction notice and the
      prescriber's explanations on the correct use of the Autohaler and second, to
      determine the profile of subjects most refractory to its correct use. The study
      was conducted by general practitioners in 2,467 asthmatic subjects with poor
      inhaler technique. The Autohaler was used correctly right from the start in 42.8%
      of subjects simply after reading the instruction notice (phase I) and in 68% of
      subjects after receiving the prescriber's explanations (phase II). At the end of
      phases I and II, correct use was performed by 82% of subjects. After
      stratification and adjustment, the probability of incorrect use, derived from the
      odds ratio: i) increased by 80% between 35 and 64 years of age and by 280% beyond
      65 years; ii) was 30% higher in cases of severe asthma; iii) was 50% higher in
      cases of regular use of a pMDI and 80% higher in the absence of previous
      treatment with inhalers; iv) was 2.5 times lower in subjects who had a secondary
      education and 5 times higher in those with a university education; v) was not
      correlated with either sex or habitation. We conclude that the breath-actuated
      inhaler Autohaler allow correct treatment in 82% of poor inhaler technique
      patients after reading the instruction notice and brief prescriber's explanation,
      but some patients, elderly or low level of education, must be given clear,
      detailed and continuing information.

PMID- 9181148
TI  - [Benign mediastinal opacity: Castleman disease, apropos of a case and review of
      the current literature].
AB  - We report a case of fortuitously observed Castleman's disease. An mediastinal
      opacity was observed on the chest x-ray. At surgery, the apparently benign tumor
      was well individualized. Pathology reported Castleman's disease. Pathogenesis is
      unknown. Recent data on localized and more diffuse forms of this disease are
      presented. Diffuse forms occur more readily in immunodepressed patients.

PMID- 9181149
TI  - [A rare cause of Pierre Marie hypertrophic osteoarthropathy: subacute infectious
      endocarditis].
AB  - Secondary hypertrophic osteoarthropathy occurred in a patient with subacute
      endocarditis. Chest x-ray in this smoker with ethylic cirrhosis showed a
      pulmonary opacity. Clinical signs of osteoarthropathic inflammation resolved with
      antibiotics before surgical cure of the aortic insufficiency. The diagnosis was
      retained on the basis of outcome after antibiotic therapy and the absence of any
      other etiology, notably bronchogenic cancer. Endocarditis or infectious
      endarteritis should be entertained in case of hypertrophic osteoarthropathy in
      patients with an infectious syndrome. Pathogenic hypotheses are discussed. In
      congenital cardiopathies, intrapulmonary shunts, megacaryocytes and activation of
      the vascular-platelet endothelium unit may be involved. Bacterial factors and
      platelet aggregation could play a role in initiating hypertrophic
      osteoarthropathy in patients with infectious endocarditis.

PMID- 9181150
TI  - [Congenital cystic adenomatoid degeneration of the lung and ventricular
      trigeminism at adult age. Is there a cause-effect relation?].
AB  - Adenomatoid cystic malformations of the lung are usually diagnosed during the
      perinatal period. Its occurrence in adults is rare, this being the fifth case
      reported in literature. Improved follow-up techniques and in utero treatment have
      considerably improved prognosis. Differential diagnosis of pulmonary cysts should
      thus include this entity at all ages. Recurrent infection is usually the
      inaugural sign although all neighboring organs, including the heart, may be
      involved due to compression or extension of the inflammation. Clinical diagnosis
      is suggested by radiographic findings and is confirmed at pathology as surgery is
      generally indicated.

PMID- 9181151
TI  - [A rare cause of chronic respiratory insufficiency: arthrogryposis in adults].
AB  - Arthrogryposis is a congenital disease leading to multiple joint ankylosis in
      utero observed as sequellae at birth. Deformation of the chest produces
      respiratory failure usually seen at birth. We report a case in an adult which
      required intermittent nocturnal positive pressure nasal ventilation.

PMID- 9181152
TI  - [Aneurysms of the pulmonary artery in Behcet disease. Apropos of 5 new cases].
AB  - Behcet's disease is a systemic vascularitis generally involving the venous
      system. Many organs may be involved, but pulmonary localizations are uncommon. We
      report 5 cases of pulmonary artery aneurysms observed in a series of Behcet's
      disease collected over a 10-year period. All patients were males, age range 18-41
      years. Hempotysia was the inaugural event in all cases. Behcet's disease was
      recognized in only 2 of the patients initially. The diagnosis was made after
      recognition of the pulmonary artery aneurysms in the others. Chest x-ray showed
      round perihilar opacities varying in number from 2 to 4. Computed tomography with
      vascular opacification was performed in 4 patients and confirmed the aneurysmal
      nature of the opacities. Angiography was performed in 3 cases. Medical treatment
      with corticosteroids and/or colchicine was prescribed in all cases. One patient
      had left inferior lobectomy. In one case regression of the aneurysms precluded
      embolization. Two patients refused surgery and in one, surgery was not retained
      due to the large number of aneurysms. Outcome was fatal in one patient who died
      after cataclysmic hemoptysia. These findings underline the uncommon nature of
      pulmonary aneurysms in Behcet's disease and the diagnostic difficulties
      encountered in absence of specific signs as well as the poor prognosis of such
      localizations.

PMID- 9181153
TI  - [Hemoptysis caused by pulmonary arterial aneurysm, disclosing Behcet disease.
      Apropos of 2 cases].
AB  - Behcet's disease, frequent in our region, can have many clinical presentations.
      Arterial lesions generally lead to poor prognosis. We report two cases of
      pulmonary artery aneurysm in two young adults whose Behcet's disease was revealed
      by hemoptysia.

PMID- 9181154
TI  - Intrathecal morphine for post-sternotomy pain in patients with myasthenia gravis:
      effects on respiratory function.
AB  - BACKGROUND: Thymectomy can induce a remission or at least an improvement in
      myasthenia gravis (MG) patients. After sternotomy MG patients with compromised
      muscle strength need an excellent postoperative pain relief. This study was
      designed to evaluate the efficacy of intrathecal morphine (ITM) on ventilatory
      function among MG patients undergoing trans-sternal thymectomy, when intravenous
      morphine served as control. METHODS: Twenty consecutive MG patients were
      randomised to receive either morphine (10 micrograms/kg) intrathecally at
      induction or intravenous morphine (30 micrograms/kg) with a patient-controlled
      analgesia (PCA) device. Anaesthesia was standardised. Forced vital capacity
      (FVC), forced expiratory volume in 1 s (FEV1), respiratory rate, oxygen
      saturation, arterial blood gases, pain intensity and morphine consumption were
      assessed during 48 hours. RESULTS: The mean age of the patients was 35 +/- 3.4
      years and the mean duration of the disease 1.9 +/- 0.5 years. According to
      Osserman's classification 70% of the patients belonged to Class IIA and 30% to
      Class IIB. ITM restored ventilatory function significantly better than iv PCA
      morphine. FVC recovered to 60% and FEV1 to 57% of the baseline values in the ITM
      group compared with 32% (P < 0.05) and 37% in the PCA morphine group,
      respectively. Postpuncture headache occurred in 4/10 patients. CONCLUSION:
      Intrathecal morphine provided effective postoperative analgesia and significantly
      improved ventilatory function when compared with intravenous morphine.

PMID- 9181155
TI  - Motor power pharmacodynamics of subarachnoid hyperbaric 5% lidocaine in the
      sitting position.
AB  - BACKGROUND: Repetitive dynamometric measurement using a plantar flexion power
      device (PFPD) provides detailed data describing the onset and offset of motor
      block following spinal administration of lidocaine. The aim of this study was to
      evaluate administration of two doses of spinal lidocaine in the sitting position
      to determine whether our dynamometric model produces data consistent with our
      current understanding of the pharmacokinetics of subarachnoid, hyperbaric, 5%
      lidocaine. METHODS: Twenty male patients (54 to 80 yr) undergoing cystoscopy
      received spinal anaesthesia with either 75 mg (n = 10) or 100 mg of hyperbaric
      lidocaine 5%, in the sitting position, under standardised conditions. Plantar
      flexion muscle power was recorded during onset and offset of anaesthesia using a
      load cell interfaced with a computer (PFPD). RESULTS: Onset of paralysis
      following spinal block in the sitting position was rapid and complete with motor
      power declining exponentially to 5% of preoperative values by 8.5 min in all
      patients. There was no difference in decay or recovery of plantar flexion motor
      power data between dosage groups in the sitting position. Measurement using the
      PFPD shows that onset of motor paralysis is described by an exponential decay and
      that motor recovery occurs at a fixed rate. Extent of block to cold and pinprick
      was similar in both dosage groups in the sitting position (median T4).
      CONCLUSION: This study shows that in the sitting position, doses less than 75 mg
      of 5% hyperbaric lidocaine are required to significantly improve ambulatory
      times.

PMID- 9181156
TI  - The use of central regional anesthesia techniques in Sweden: results of a nation
      wide survey. Swedish Association of Anesthesia and Intensive care.
AB  - BACKGROUND: Epidural and subarachnoid anesthesia are well established central
      regional techniques for surgical anesthesia. Two additional techniques, combined
      spinal epidural (CSE) block and continuous spinal anesthesia (CSA), have recently
      become popular. However, data on nation-wide use of central regional blocks are
      not available. METHOD: With the aims to survey the use of central regional
      techniques, to evaluate the risk of complications to central regional blocks and
      to document the use of continuous epidural techniques for postoperative pain
      management in Sweden during 1993, a questionnaire was mailed to all 105 Swedish
      anesthesiology departments. RESULTS: Questionnaires were returned by 62
      departments, representing all categories of Swedish hospitals. Central regional
      blocks were used for surgical anesthesia in 20-40% of reported surgical
      procedures. Subarachnoid anesthesia was the main technique for orthopedic surgery
      on the lower limb, elective cesarean section and transurethral resection of the
      prostate. Epidural block was used for orthopedic and vascular surgery. CSE block
      was used by 42 departments and CSA by 21 departments. Postoperative epidural
      analgesia was used by 59 departments, most commonly with continuous infusion of
      local anesthestics and/or epidural bolusdoses of morphine. Nineteen neurological
      sequelae were reported after epidural (n = 7) and subarachnoid (n = 12) blocks.
      Routines for registration of complications varied greatly. CONCLUSIONS:
      Subarachnoid block was preferred for shorter surgical procedures (< 60 min),
      whereas epidural and CSE blocks were chosen when severe postoperative pain could
      be anticipated, as continuous epidural analgesia was well established for
      postoperative pain management. Improved routines for registration of
      complications to central regional blocks are needed.

PMID- 9181157
TI  - Postoperative analgesia in Italy. National survey on the anaesthetist's beliefs,
      opinions, behaviour and techniques in postoperative pain control in Italy.
AB  - BACKGROUND: Using a personal, anonymous questionnaire developed ad hoc, we tried
      to document the role, the problems and the activities of Italian anaesthetists in
      postoperative pain control. METHODS: A random selection-stratified by region-was
      made from a list of 971 hospitals. The final sample was made up of 395
      departments of anaesthesia and intensive care from 369 hospitals. The
      completeness and consistency of each questionnaire were assessed. RESULTS: The
      response rate achieved was 78.9% (312 centres in 293 hospitals) with 2435
      evaluable questionnaires corresponding to 30% of all Italian anaesthesia
      departments and 25% of Italian anaesthetists. Only 15.2% of anaesthetists are
      completely responsible for the postoperative analgesia (POA) (prescriptions and
      evaluations) and an established attitude for POA (protocols/guidelines) exists in
      18 departments only. 60% of anaesthetists use routinely the intramuscular route,
      55.2% the intravenous route (infusion plus bolus), and 23.7% the spinal/epidural
      route. Only 6.2% of the anaesthetists use the patient-controlled analgesia
      system. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used
      agents (47% NSAID vs 37.9% opioids; NSAID-opioid association 14.7%). A local
      anesthetics-opioids association is preferred for the spinal/epidural route
      (15.1%) only (local anaesthetic 4.9% only; opioids alone 2.7%). Lack of time,
      work organization, technique knowledge/training, trust in nursing-ward staff,
      difficulty in monitoring the patient on the ward, concern about opioid use
      leading to ventilatory depression, and administration errors are reported to be
      the main factors that limit an appropriate approach to postoperative pain (POP),
      the correct use of analgesics and a free choice of POA technique. CONCLUSION:
      This survey shows that Italian anaesthetists do not consider the postoperative
      period to be their own personal work area and that POA is to be considered as a
      matter of individual choice.

PMID- 9181158
TI  - Intravenous phentolamine test--an aid in the evaluation of patients with
      persistent pain after low-back surgery?
AB  - BACKGROUND: Persistent pain following surgery in the treatment of chronic low
      back pain patients is still relatively frequent. Most of these patients with
      persistent pain have clinical signs of neuropathic pain. The neuropathic pain
      might be sympathetically maintained pain (SMP) or sympathetically independent
      pain (SIP). Systemic administration of phentolamine, a competitive alpha
      adrenergic antagonist, has been used as a diagnostic tool to identify patients
      with SMP. METHODS: Thirty-seven patients with persistent pain after low-back
      surgery (lumbar laminectomy, with or without discectomi, or a posterior fusion,
      with or without decompression) received intravenous phentolamine (0.5 mg/kg over
      30 min) in a single-blind, placebo-controlled manner. Prior to this infusion the
      patients were classified clinically into different pain groups based on physical
      examination and imaging findings. An opioid epidural test blockade was used as a
      control. RESULTS: Clinical classification divided the patients into nociceptive
      pain (n = 7), neuropathic pain (n = 22) and mixed pain (n = 8). In the
      phentolamine test there were only one responder, 34 non-responders and 2 patients
      were placebo-responders. In the control epidural blockade there were 11 non
      responders, 23 fentanyl/local anaesthetic-responders and 3 placebo-responders.
      CONCLUSIONS: SMP is either an uncommon cause of persistent pain in this type of
      failed back surgery patients or the phentolamine test, as we performed it, was
      unable to identify SMP.

PMID- 9181159
TI  - Segmental effects on motor function following different intrathecal receptor
      agonists and antagonists in rabbits.
AB  - BACKGROUND: The occurrence of motor impairment after intrathecal drug
      administration is infrequently reported in the literature and the methods of
      determining motor function vary. METHODS: Motor function was examined in rabbits
      after a wide dose range of a variety of intrathecally administered opioid
      agonists, alpha-adrenergic agonists, non-competitive NMDA antagonists, a
      benzodiazepine agonist, a sigma agonist, paracetamol, isotonic and acidified
      saline. The opioids, sigma agonist and NMDA antagonists were additionally
      examined following pretreatment with naloxone. The opioid antagonists naltrindole
      and MR2266 (delta- and kappa-opioid receptor antagonists, respectively) were
      administered before the delta agonist and the kappa agonist. The alpha 2
      adrenergic antagonist yohimbine was given before administration of
      dexmedetomidine and xylazine. Motor function was evaluated by a five-point scale
      of motor impairment ranging from normal function to total paralysis of the
      hindlegs. RESULTS: DPDPE (delta agonist), paracetamol, naloxone, naltrindole,
      yohimbine, isotonic and acidified saline did not affect motor function. MR2266
      produced minor motor impairment. The alpha-adrenergic agonist dexmedetomidine
      reduced motor function slightly and dose independently. The remaining compounds
      affected motor function in a dose-dependent fashion. High doses of morphine
      produced hypersensitivity and myoclonus. An irreversible paralysis of the
      hindlegs was observed following intrathecal administration of the sigma agonist
      SKF10047 in high doses. Naloxone and MR2266 attenuated the effects of U50488H
      (kappa agonist). CONCLUSION: The present results reveal a dose-dependent
      reduction in motor function after intrathecal administration of some of the
      investigated compounds. The mechanisms behind these effects appear to be
      multifactorial.

PMID- 9181160
TI  - Bupivacaine does not suppress cardiac sympathetic nerve activity during halothane
      anesthesia in the cat.
AB  - BACKGROUND: The finding that i.v. lidocaine suppresses cardiac sympathetic nerve
      activity during 1 MAC halothane, but not during 2 MAC or 3 MAC halothane,
      suggests that the neurally mediated circulatory effects of i.v. local anesthetics
      may vary with background autonomic activity. This study aimed to compare the
      effects of i.v. lidocaine and bupivacaine on cardiac sympathetic nerve activity
      (CSNA) during normal and high levels of CSNA. METHODS: Cats were anesthetized
      with halothane and allocated to three groups. In groups I-L and I-B, sympathetic
      hyperactivity was induced by electrical stimulation of the posterior
      hypothalamus. CSNA, heart rate and mean arterial pressure were then measured
      before and after administration of lidocaine 2 mg.kg BW-1 i.v. (Group I-L, n = 7)
      or bupivacaine 0.5 mg.kg BW-1 i.v. (Group I-B, n = 7) during 1% halothane
      anesthesia. In Group II (n = 7), following administration of bupivacaine 0.5
      mg.kg BW-1 i.v., CSNA, sinus cycle length (SCL), and subintervals of
      atrioventricular conduction time (A-H, H-V, and H-S) at pacing were measured
      during 0.8%, 1.6% and 2.4% halothane anesthesia without sympathetic
      hyperactivity. RESULTS: Lidocaine suppressed CSNA hyperactivity and tachycardia
      significantly in Group I-L, but bupivacaine did not do so in Group I-B. In Group
      II, bupivacaine did not affect CSNA at any concentrations of halothane, but
      lengthened SCL, A-H, H-V and H-S intervals significantly at each concentration of
      halothane. CONCLUSIONS: We conclude that i.v. bupivacaine, unlike i.v. lidocaine,
      does not suppress CSNA during either normal or high CSNA under halothane
      anesthesia although i.v. bupivacaine has stronger depressive effects on cardiac
      conduction than does i.v. lidocaine during deep halothane anesthesia.

PMID- 9181161
TI  - The effect of patient positioning on dynamic lung compliance.
AB  - BACKGROUND: Side-stream spirometry offers a non-invasive method to monitor
      continuously respiratory mechanics in intubated patients. We studied the effects
      of different positions on dynamic lung compliance during anaesthesia. METHODS:
      The study consisted of 56 patients, operated in supine, prone, kneeling or
      lateral park-bench position. Dynamic lung compliance and inspiratory peak
      pressure were recorded after induction of anaesthesia, 15 min and 1 h after
      posturing the patient. RESULTS: The first measured compliances were comparable in
      all groups. The compliance in the lateral and the prone positions was
      significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P <
      0.001) after the posture change. The peak inspiratory pressure was significantly
      lower in the kneeling position than in the other groups (P < 0.01 at the first
      measurement, P < 0.001 at the later measurements). No correlation was found
      between body mass index and compliance. CONCLUSION: We found that dynamic lung
      compliance decreased significantly upon change of posture from supine to lateral
      or prone position, whereas in the kneeling position no change in compliance was
      observed. We suggest that the kneeling position might be preferable to the prone
      position.

PMID- 9181162
TI  - Elastic work of breathing during continuous positive airway pressure in intubated
      patients with chronic obstructive pulmonary disease (theoretical analysis and
      experimental validation).
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is known to decrease
      inspiratory work of breathing in patients with chronic obstructive pulmonary
      disease (COPD). This effect is primarily attributed to a reduction in inspiratory
      elastic work of breathing (Wi,el) related to a decrease in intrinsic positive end
      expiratory pressure (PEEP). METHODS: The aim of this study is to design a model
      for computation of Wi,el on the basis of respiratory mechanics in patients with
      COPD, at various intrinsic PEEP- and CPAP-levels. The model was used to estimate
      the optimal CPAP-level with respect to the intrinsic PEEP-level in terms of
      reduction of Wi,el. Calculations of the decrease in Wi,el due to CPAP obtained
      with the model were compared to changes in Wi,el and total work of breathing
      (Wi,tot) determined from respiratory measurements in patients with COPD. RESULTS:
      Model calculations revealed that Wi,el was minimal whenever a CPAP-level equal to
      the intrinsic PEEP-level was applied. When a CPAP-level exceeding the intrinsic
      PEEP-level was applied, the reduction in Wi,el was less. Comparing these results
      to the respiratory measurements, a similar pattern in reduction of Wi,el and
      Wi,tot was established, although absolute values of the differences were smaller
      in the experimental data. CONCLUSION: This study indicates that in order to
      reduce Wi,el in patients with COPD, intrinsic PEEP should be measured and the
      CPAP-level adjusted to the intrinsic PEEP-level.

PMID- 9181163
TI  - The effect of acute normovolemic hemodilution on homologous blood requirements
      and total estimated red blood cell volume lost.
AB  - BACKGROUND: Acute normovolemic hemodilution combined with retransfusion is one of
      the various techniques proposed to avoid homologous blood transfusion in cardiac
      surgery. The purpose of the present paper is to study the effect of the volume of
      autologous blood collected pre-cardiopulmonary bypass (CPB) on homologous blood
      requirements and total estimated red blood cell (RBC) volume lost in coronary
      artery bypass grafting (CABG) surgery. METHODS: Following induction of
      anesthesia, sequestration of one (5-8 ml/kg; Group I, n = 14) or two units (12-15
      ml/kg; Group II, n = 14) of fresh autologous blood was performed under
      electrocardiographic and hemodynamic control. Group III (n = 14) was designated
      as the control group. Autologous blood was reinfused at the conclusion of CPB.
      RESULTS: The use of homologous blood in the study groups was significantly less
      than in the control group. High-volume phlebotomy did not make a significant
      difference in the requirement of the homologous blood, while causing a mild
      increase in the total estimated RBC volume lost. No significant differences could
      be demonstrated in preoperative, post-CPB and discharge hematocrit levels and
      postoperative blood drainage between the groups. CONCLUSION: Acute intraoperative
      hemodilution with high- and low-volume phlebotomy reduced the homologous blood
      requirements similarly regardless of the amount of phlebotomy.

PMID- 9181164
TI  - Maintained cardiac output during positive end-expiratory pressure ventilation in
      open-chest pigs.
AB  - BACKGROUND: Does ventilation with positive end-expiratory pressure (PEEP) act to
      reduce cardiac output (CO) not only by impeding venous return but also by
      inducing myocardial depression? The present study was aimed to demonstrate the
      possible existence of this latter mechanism. METHODS: Eight pigs of Swedish
      native breed weighing 20-25 kg and 10-12 weeks old were anaesthetized,
      tracheotomized and connected to a volume-controlled ventilator. To prevent
      intrathoracic pressure from interfering with venous return, the heart and
      juxtacardiac vessels were exposed to atmospheric pressure by opening and
      retracting the chest and pericardium. Heart rate (HR), CO, stroke volume (SV),
      mean arterial (MAP), mean right (MRAP) and left (MLAP) atrial pressures were
      recorded before and after retransfusion of 500 ml of autologous blood. This
      procedure was carried out twice in each animal-during ventilation with zero and
      with 15 cm H2O of PEEP. RESULTS: Comparison of the two ventilation modes before
      volume load revealed negligible differences in HR, CO, SV, MAP, MRAP and MLAP.
      Moreover, the changes evoked by volume load were practically identical.
      CONCLUSIONS: Addition of PEEP to regular positive pressure ventilation does not
      induce any haemodynamically detectable myocardial depression in the piglet.

PMID- 9181165
TI  - Amrinone improves lung compliance in patients receiving mechanical ventilation
      for cardiogenic pulmonary edema.
AB  - BACKGROUND: Decrease in lung compliance is one of the major causes of respiratory
      failure. We investigated whether amrinone could improve lung compliance. METHODS:
      We selected 20 consecutive patients with respiratory failure due to severe
      cardiogenic pulmonary edema to receive mechanical ventilation. Patients were
      administered a bolus injection (1 mg.kg-1) over 10 min followed by continuous
      intravenous infusion (10 micrograms.kg-1.min-1) of amrinone. Lung compliance,
      blood gas values, hemodynamic parameters, and sample plasma amrinone levels were
      assessed over a 120-min period after the onset of the continuous infusion of
      amrinone. RESULTS: Ten min following amrinone infusion, dynamic compliance (Cdyn)
      and static compliance (Cst) increased from 30 +/- 11 to 36 +/- 12 ml/cm H2O and
      from 37 +/- 12 to 42 +/- 13 ml/cm H2O, respectively (P < 0.01). Plasma amrinone
      levels reached a therapeutic level as vasodilator and positive inotropic effects
      at 10 min after amrinone infusion. The significant change in mean pulmonary
      artery pressure and pulmonary artery wedge pressure occurred later than the
      change in compliance of respiratory system. However, there were significant
      correlations between the mean pulmonary artery pressure and Cdyn (r = 0.36, P <
      0.01) and Cst (r = 0.44, P < 0.01), as well as between plasma amrinone levels and
      Cdyn (r = 0.30, P < 0.05) and Cst (r = 0.41, P < 0.01). CONCLUSIONS: Amrinone
      induced improvement in lung compliance was considered mainly to be due to an
      increase in the number of functioning lung units by improvement of the
      hemodynamics and a direct positive effect of amrinone on respiratory muscle
      contraction.

PMID- 9181166
TI  - A survey of the ASA physical status classification: significant variation in
      allocation among Finnish anaesthesiologists.
AB  - BACKGROUND: The American Society of Anesthesiologists' (ASA) Classification of
      Physical Health is a widely used grading system for preoperative health of the
      surgical patient. In previous studies conducted in North America and Great
      Britain, considerable variation in the ASA classification allocation has been
      reported. We hypothesised that in smaller and culturally more homogeneous
      countries there might be less variation in the ASA classification. METHODS: A
      postal questionnaire depicting 10 hypothetical patient cases was sent to 249
      randomly selected members of the Finnish Society of Anaesthesiologists. Responses
      of anaesthesiologists working in university teaching and non-teaching hospitals
      were compared, as well as the answers of specialists and non-specialists.
      RESULTS: Responses were received from 108 anaesthesiologists (response rate 43%).
      There was marked variation in the classification of all the 10 cases: 1 case was
      classified to all five possible grades (ASA grades I-V). In 2 cases, there was
      significant variation between anaesthesiologists working in university teaching
      and non-teaching hospitals. There was no difference in the grading between
      specialist and non-specialist anaesthesiologists. CONCLUSION: In a small and
      culturally homogeneous country, like Finland, there exists similar wide variation
      in the ASA classification as has been previously reported from larger and
      culturally more heterogeneous countries. The significant variation should always
      be considered when using this classification in clinical or scientific work.

PMID- 9181167
TI  - Propofol induces a lowering of free cytosolic calcium in myocardial cells.
AB  - BACKGROUND: The intravenous anaesthetic drug propofol has been shown to depress
      myocardial contractility. Ketamine, on the other hand, is a well-documented
      cardiovascular stimulant. These differences could possibly be due to different
      effects of the drugs on the calcium homeostasis of the myocardium. METHODS: The
      fluorescent intracellular probe fura-2 acetoxymethyl ester (fura-2/AM) was used
      in this in vitro investigation to study the influence of intravenous anaesthetic
      drugs on free cytosolic calcium concentration in suspensions of isolated rat
      myocardial cells. RESULTS: Addition of 0.5-2.0 micrograms/mL propofol resulted in
      a significant and dose-dependent decrease of free cytosolic calcium concentration
      in the myocardial cells, while addition of 0.25-2.5 micrograms/mL ketamine did
      not affect this concentration significantly. CONCLUSION: The results imply that
      the previously demonstrated negative inotropic effect of propofol could possibly
      be related to its influence on calcium availability in the myocardium.

PMID- 9181168
TI  - Effect of temperature variation (22 degrees C-44 degrees C) on halothane and
      caffeine contracture testing in normal humans.
AB  - BACKGROUND: Malignant hyperthermia (MH) susceptibility is diagnosed using
      halothane-caffeine contracture testing of a muscle sample maintained at 37
      degrees C. However, there has not been a systematic study that examines the
      effect of different temperatures on the response of normal muscle to halothane
      and caffeine. We hypothesized that altering bath temperature would modify the
      contracture responses. METHODS: We obtained muscle samples from 20 patients
      undergoing surgical procedures of the lower extremities. The samples were
      dissected into 245 bundles and the bundles were exposed to halothane 3% or
      incremental caffeine, according to the North American MH group protocol. Several
      bundles from each patient were simultaneously studied at four different
      temperatures (22 degrees C, 30 degrees C, 37 degrees C and 44 degrees C). Each
      bundle was studied at only one temperature, the muscle samples of 3 patients were
      simultaneously studied at all four temperatures for halothane and caffeine.
      RESULTS: Maximum contracture to caffeine (32 mM) was highest at 37 degrees C;
      however, at lower caffeine concentrations (2-4 mM), there was no consistent
      effect of temperature on contracture response. Likewise, temperature did not
      alter contracture responses to halothane. The extremes of temperature (22 degrees
      C and 44 degrees C) were associated with lack of twitch in response to electrical
      stimulation. For the bundles exposed to halothane at 22 degrees C, the absence of
      a twitch was associated with the presence of a contracture, although these were
      never above the diagnostic threshold. CONCLUSIONS: We conclude that temperature
      has little effect on responses of normal muscle to halothane and caffeine.

PMID- 9181170
TI  - Reversal of multiorgan system dysfunction in sickle cell disease with plasma
      exchange.
AB  - A 23-year-old man with sickle cell anemia and multiorgan system dysfunction was
      treated with plasma exchange during a sickle cell crisis. The patient failed to
      respond to conventional treatment including hydration, blood transfusions, broad
      spectrum antibiotics, supplemental oxygen, and analgesics. The clinical picture
      resembled thrombotic thrombocytopenic purpura (TTP), and the patient responded
      dramatically to plasma exchange with reversal of a rapidly deteriorating clinical
      state. This case illustrates possible similarities in the pathophysiology of TTP
      and sickle cell crisis, and the value of plasma exchange in related critical
      disease states.

PMID- 9181169
TI  - Large increase in cardiac output in a patient with ARDS and acute right heart
      failure during inhalation of nitric oxide.
AB  - BACKGROUND: Inhaled nitric oxide (NO), a selective pulmonary vasodilator, reduces
      pulmonary artery pressure in patients with acute respiratory distress syndrome
      (ARDS). In spite of the reduction of right ventricular afterload, the effect of
      NO on cardiac output remains unclear. METHODS: A patient with ARDS and
      echocardiographically determined severe acute right heart failure was treated
      with increasing concentrations of inhaled nitric oxide (NO). Haemodynamic and gas
      exchange variables were determined for each concentration of NO. NO treatment was
      continued for 3 days. RESULTS: During initial right heart failure, administration
      of NO resulted in a large increase (32%) in cardiac output in a dose-dependent
      manner. When right ventricular function had improved, inhalation of NO did not
      increase cardiac output. CONCLUSION: Our observations suggest that inhalation of
      NO is likely to increase cardiac output in ARDS when severe acute right heart
      failure is present.

PMID- 9181171
TI  - Intraoperative epidural catheter malfunction in two obese patients.
AB  - Using a combined general anesthesia/epidural technique, two cases of
      intraoperative malfunctioning epidural catheters in obese patients are presented.
      After the epidural was found to be malfunctioning, the anesthesiologist placed
      the palm of both hands underneath the patients' lumbar and thoracic area. The
      epidural catheter with tape and subcutaneous tissue was pulled in both cases
      towards the head. In each case, this simple maneuver made the catheter function
      again. In conclusion, this simple corrective maneuver should be attempted prior
      to discarding the epidural anesthetic technique.

PMID- 9181172
TI  - Premedication in Danish anaesthesia departments 1994/95.

PMID- 9181173
TI  - Eldor needle's advantage over the needle-through-needle technique.

PMID- 9181174
TI  - Investigation on seasonality of twin births in Brazil.
AB  - The hypothesis of seasonality of twin births was investigated in two important
      maternity hospitals in the State of Sao Paulo, Brazil. The study included 1,386
      twin births that occurred among 154,699 deliveries from 1984 to 1993. No evidence
      of seasonality has been detected either for the twin birth rate considered as a
      whole or for dizygotic twinning rate. The distributions of these rates fitted
      well sinusoidal regression curves but the cyclic trend did not correspond to any
      specific season.

PMID- 9181175
TI  - Life situation, self reported health and coping ability of 35-year old twins and
      controls--a follow-up of a longitudinal Swedish twin study at adolescence.
AB  - During the years 1964 to 1971 a nationally representative sample of MZ and DZ
      twins and controls was followed through the Swedish compulsory school. The main
      purpose was to study physical and mental growth during puberty as well as
      heredity-environment influences on these growth processes. After 20 years a
      follow-up has been made of this sample with the purpose of investigating heredity
      environment influences on life situation and self reported health at mid-life in
      relation to background factors collected during adolescence. 43 pairs of MZ
      twins, 90 pairs of DZ same sex and opposite sex twins as well 322 controls agreed
      to participate. A questionnaire was sent out to this group dealing with their
      present life situation such as family structure, economy, education and
      occupation. Other areas of interest were self reported health and ability to cope
      with their present life situation. The disadvantages found for MZ female twins at
      adolescence seem to persist at mid-life and ratings of school adjustment were
      related to coping ability as grown ups. This first report presents comparisons
      between twins and controls as well as males and females. To estimate heredity
      influences intraclass correlations for the twin pairs are calculated and for
      coping ability such influences seem to be quite conspicuous. Sex specific factors
      seem to operate regarding coping ability and satisfaction in educational choice
      and level. Generally, the results-indicate some advantages for the males
      regarding self reported life situation and health. Possible reasons for such sex
      differences are discussed. This study has been supported by grants from the
      Swedish Council for Social Research.

PMID- 9181176
TI  - Earnings and schooling: an overview of economic research based on the Australian
      Twin Register.
AB  - This paper reviews four economic studies of aspects of earnings and schooling
      conducted by the authors using data from the Australian Twin Register. First,
      estimates of the economic returns to schooling made using fixed effects and
      selection effects regression models incorporating an instrumental variables
      approach to correct for measurement error in self-reported schooling levels are
      examined. The finding is that up to 30 per cent of the estimated return to
      schooling may be due to family effects and the remainder to pure educational
      effects. Second, comparisons are made between the economic model of Ashenfelter
      and Krueger (1994) and that of DeFries and Fulker (1985) and the results obtained
      from each are shown to be similar. Third, gender differences in returns to
      schooling are estimated and family effects are found to be a more important
      influence in the case of males. Fourth, the influence of family effects on
      educational attainments is considered and it is found that around one-half of
      educational attainment is accounted for by genetic inheritance and up to another
      quarter due to shared environment effects.

PMID- 9181177
TI  - Study on possible increase in twinning rate at a small village in south Brazil.
AB  - A high frequency of twin births has been observed in Linha Sao Pedro, a small
      settlement which belongs to the city of Candido Godoi, located 524 km Northwest
      from Porto Alegre, Rio Grande do Sul, Brazil, in an ethnically homogeneous
      population of German descent restricted to a small geographic region. From 1990
      to 1994, the proportion of twin births in Linha Sao Pedro was 10%, significantly
      higher than the 1.8% rate for the state of Rio Grande do Sul as a whole.
      Genealogical analysis showed a high recurrence of multiple births within
      families, as well as a high level of inbreeding in the community. Zygosity data
      indicated that 9 of the 17 pairs of twins studied (53%) were dizygotic. No
      external environmental factors were detected that could be influencing the
      appearance of this characteristic. This preliminary investigation confirmed the
      presumed existence of a high twinning rate in the community. The high familial
      recurrence and the high inbreeding rate suggests the presence of genetic twinning
      factors. Complementary studies of twins that have yet to be evaluated and the
      search for additional risk factors, as well as linkage studies, should contribute
      to a further understanding of the biological factors related to twin births in
      the human species.

PMID- 9181178
TI  - Temperament development to 30 months of age in discordant twin pairs.
AB  - Twins within pairs often have different weights at birth. A difference of 15% or
      greater is defined as discordance for weight and is considered to place one or
      both infants at risk. Temperature differences had been found in the neonatal
      period for fullterm discordant cotwins, but not for preterm discordant cotwins,
      suggesting that continued gestation for discordant twins was a risk variable for
      early behavior. 30 pairs of fullterm and 17 pairs of preterm discordant pairs
      were followed at 6, 9, 12, 18, 24, and 30 months of age. Group differences were
      observed for the longitudinal maintenance of cotwin discordance in physical
      measures, with preterm cotwins becoming more like each other. In laboratory
      assessments, temperament differences no longer were observed between the larger
      and smaller cotwins. Questionnaires indicated that mothers generally did not
      differentiate between their larger and smaller cotwin children in temperament
      ratings, except for ratings of mood for the fullterm pairs. Thus, emotionality
      was the only temperament dimension that differentiated between the fullterm
      discordant twins both in the neonatal period and at later ages. In the main, it
      was concluded that the fullterm discordant twins overcame the adverse in-utero
      influences on early behavioral development.

PMID- 9181179
TI  - Field dependence and characteristics of conceptualization in identical twins.
AB  - This study falls in the areas of both differential psychology and twin
      psychology. Using the EFT and the WCST (computerized version), we examined 11
      MZFF pairs between 18 and 35 years of age. The aim was to establish the genetic
      and/or environmental determination of global-analytical cognitive style as well
      as some characteristics of conceptualization linked to field dependence. The
      research strategy consisted of introducing three other groups of the same size to
      control the weight of environmental factors different from those determined by
      subject selection. The results seem to support the hypothesis of genetic
      determination of field dependence of the MZFFs, probably linked to the XX
      chromosome combination. The "couple effect" and the attitude of parents and
      others toward two identical female subjects may contribute to full expression of
      the genome. The characteristics of conceptualization revealed by the WCST show
      that MZFFs persevere in errors typical of a global approach to experience.

PMID- 9181180
TI  - Maternal and neonatal variables in twins: an epidemiological approach.
AB  - Population studies on human twinning are scarce in Argentina. In order to analyze
      frequencies and certain maternal and neonatal variables related to twin births,
      we studied a series of 69.678 consecutive newborns with 500 g of weight and over,
      which occurred at a public hospital in the province Buenos Aires, during 14 years
      (1982-1995). The frequency of twin births (10 per 1000 deliveries) and sex ratio
      were similar to other studies reported in Caucasian population. Maternal age and
      order of gravity/parity were positively correlated with twinning rates, more
      markedly so in dissimilar sex-pairs. Stillbirths and neonatal deaths were more
      frequent in twins than in singletons, but less frequent when comparing groups of
      same weight. Congenital malformations were not found to be significantly more
      frequent in twins than in the total newborn population. However, their
      occurrence, predominantly in like-sexed pairs and the concordance for defect type
      in doubly affected same-sex pairs, suggests that monozygotic twinning carries an
      increased risk for malformation.

PMID- 9181181
TI  - Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable
      poly-dl-lactide-co-glycolide microspheres (NET-90): phase III clinical study.
AB  - Safety, contraceptive efficacy, and acceptability of norethindrone, encapsulated
      in biodegradable poly-dl-lactide-co-glycolide injectable microspheres (NET-90),
      was evaluated for 12 months in one hundred women. Fifty-one volunteers received
      65 mg, and 49 received 100 mg of NET-90, at three month intervals,
      intramuscularly in the gluteal region. The mean NET levels at 3-month intervals
      for the 65 and 100 mg groups were, respectively, 0.32 +/- 0.16 ng/ml and 0.49 +/-
      0.25 ng/ml. No local or systemic side-effects were observed in either group. Body
      weight, blood pressure, and laboratory parameters, namely hemoglobin, hematocrit,
      lipid profile, sequential multichannel autoanalyzer computer profiles (SMAC), as
      well as PAP smear, remained within normal limits throughout the study in both
      groups. There was no pregnancy in the 65 mg group; however, one volunteer became
      pregnant in the 100 mg group. In the 65 mg group, 52.9% of menstrual cycles were
      normal, 34.5% were amenorrheic, and 12.6% showed prolonged bleeding. In the 100
      mg group, 40.6% of the cycles were normal, 52.3% were amenorrheic, and 7.1% had
      episodes of prolonged bleeding. A total of 40.3% and 36.6% of the cycles showed
      increased spotting in the 65 and 100 mg group, respectively. Our observations
      indicate that NET-90 microsphere injectables can provide a safe, efficacious, and
      acceptable method of contraception.

PMID- 9181182
TI  - Blood-lipid fractions: the side-effects and continuation of Norplant use.
AB  - OBJECTIVES: Norplant has been widely used in Indonesia, though a previous study
      conducted in Jakarta indicates that there is a significantly high cholesterol
      level in acceptors. Other international studies indicate different results.
      Accordingly, a study on the fraction of blood lipids of Norplant acceptors was
      considered necessary. MATERIAL AND PROCEDURES: A prospective cohort comparative
      study was conducted in the Dr Kariadi General Hospital and Primary Health Center
      at Gunungpati. Clinical and laboratory observations were done by means of pre
      post test design. Norplant acceptors were treated as the case group while IUD
      acceptors were the control group. Cholesterol level, triglyceride, HDL, LDL, and
      ratio of cholesterol:HDL, side-effects and continuation of use were evaluated.
      RESULTS: The subjects were 91 Norplant and 89 IUD acceptors. Norplant acceptors
      showed the following study results: Total cholesterol showed a slight decrease
      (165.06-132.80 mg/dl), triglycerides were slightly increased (76.23-81.87), HDL
      showed a decrease (45.55-38.85), and so did LDL (105.75-78.55); the ratio of
      cholesterol:HDL remained constant (3.75-3.78) and all fraction levels of blood
      lipids were within the limit of tolerance and did not exceed the critical value.
      Normal menstrual blood flow remained constant, but heavy menstrual blood flow
      decreased. The cycle of normal menstruation was reduced and the inter-menstrual
      bleeding and the 2-3 month menstrual cycle were increased. Complaints of
      dizziness/headache, leucorrhea, and pain at insertion were all relatively few.
      There was no change of body weight and blood pressure. Continuation of use was
      100%. CONCLUSIONS: The fraction of blood lipids found indicates varied results
      though blood lipids are still below critical values; it can be concluded that
      there is no risk of coronary heart disease. The continuation rate of Norplant use
      was high, due probably to side-effects counseling, and the social and cultural
      circumstances of acceptors.

PMID- 9181183
TI  - Effects of low steroid doses administered in the mid and late follicular phase on
      the LH surge, ovarian steroids and follicular maturation in eumenorrheic women.
AB  - The effects of four low doses of synthetic steroids, administered orally and
      starting on day 8 (group I) or on day 10 of the menstrual cycle (group II), upon
      LH surge, ovarian steroidogenesis, follicular maturation and menstrual cycles
      were studied in 10 eumenorrheic women. The results revealed that the day before
      the LH surge, the highest level of estrone-3-glucuronide was observed in both
      groups. Twenty-four hours after the last dose, the maximum urinary LH levels were
      recorded in groups I (day 11), and II (day 13). Pregnanediol-3 alpha glucuronide
      remained low during the study in group I, whereas in group II a gradual rise of
      this hormone starting on day 13 was registered and the highest level was found at
      day 21 of the menstrual cycle. Follicular maturation and ovulation were observed
      only in women from group II. Short and normal length cycles were recorded in
      groups I and II, respectively. In summary, low doses of exogenous synthetic
      steroids administered on day 8, but not on day 10 of the cycle, inhibit
      follicular maturation and ovulation.

PMID- 9181184
TI  - Modulation of uterine artery resistance to blood flow by the oral contraceptive
      pill.
AB  - The changes in uterine artery resistance to blood flow were studied during a
      normal ovulatory cycle (control) and during a cycle on the combined oral
      contraceptive pill in 10 healthy women, aged 18-35 years, using transvaginal
      color Doppler imaging. Ovulation was monitored using ultrasound and hormonal
      assays during both cycles. The Pulsatility Index (PI) was used as a measure of
      uterine artery resistance, on days 8 (midproliferative) and 22 (midluteal) of the
      control cycle and on days 22 (maximal ovarian suppression) and 28 (minimal
      ovarian suppression) of the pill cycle. During the pill cycle, the uterine artery
      resistance decreased from a mean PI = 4.37 (range 2.4-7.95) on day 22 to a mean
      of 2.79 (1.94-4.99) on day 28, p = 0.006. The uterine artery resistance was
      significantly higher on day 22 during the pill cycle compared to the same day of
      the control cycle, p < 0.0001. Anovulatory cycles on the oral contraceptive pill
      are associated with an increase in uterine artery resistance and a decrease in
      uterine perfusion, this effect being reversed during the pill-free week.

PMID- 9181185
TI  - Midtrimester termination of complicated pregnancy with oral misoprostol.
AB  - To define the mean effective dose of oral misoprostol, a PGE2 methylanalogue, for
      terminating midtrimester complicated pregnancy without producing significant side
      effects and complications, forty-two patients with intrauterine complicated
      pregnancies of 14-28 weeks were treated with oral misoprostol. All patients were
      observed after the initial dose (200 micrograms). If there was no contraction of
      the uterus or no vaginal bleeding, a supplementary dose of 200 micrograms
      misoprostol was given once each hour, with an average total dose of 1000
      micrograms being given (min. 200 micrograms, max. 1200 micrograms). Abortion was
      successfully induced in 39 women (92.9%); there were 3 failures (7.1%). The mean
      time from initial dose to abortion was 9 h. No important side-effects or
      complications were noted. This study demonstrated that the use of oral
      misoprostol is a simple, inexpensive and easy procedure for termination of second
      trimester complicated pregnancy.

PMID- 9181186
TI  - Oral contraceptives and breast cancer risk.
AB  - Because of the continuing controversy on the breast cancer risks associated with
      the use of combined oral contraceptives (OCs), the medical literature was
      reviewed to assess the risks of this cancer to OC users. This review found that
      the medical literature supports the view that OC use is associated with small
      increased risks of premenopausal breast cancer. There is no consensus as to which
      subgroups of women might be at an increased risk.

PMID- 9181187
TI  - Intrauterine device and pelvic inflammatory disease.
AB  - The IUD ML Cu375 was inserted, after bacteriological screening, into 620 women
      who were observed for 12 months. Bacterioscopy and, when needed, bacteriology of
      vaginal smears were performed 7 days, and 1, 3, 6 and 12 months after insertion.
      During the 12 months, pelvic inflammatory disease (PID) was diagnosed in 4
      patients (0.6%) and sexually transmitted disease (STD) in 73 patients (11.8%).
      Careful selection of patients and bacteriological screening can effectively
      reduce the risk of bacterial contamination and subsequent development of PID.

PMID- 9181188
TI  - Macho man.

PMID- 9181189
TI  - Piriformis compression causing low back and lower extremity pain.

PMID- 9181190
TI  - Pectoralis tendon and pectoralis muscle injuries.

PMID- 9181191
TI  - Physeal surgery: indications and operative treatment.
AB  - The evaluation and treatment of problems that can be corrected by surgery on the
      growth plate have changed somewhat in recent years; therefore, it is the purpose
      of this article to update the reader on these advances, as well as review the
      basic concepts. We review the radiographic evaluation of problems in the
      extremities and detail key points of physeal operative techniques for correcting
      problems occurring with growth.

PMID- 9181192
TI  - Sacroiliac joint injection: a cadaveric study.
AB  - Eleven bony pelves were studied in an attempt to find an ideal approach for
      needle placement into the sacroiliac joint and to describe the unique anatomy of
      the sacroiliac joint relative to sacroiliac joint injection. A posterior approach
      starting 2 cm to 3 cm inferior to the posterior superior iliac spine, angled 20
      degrees to 30 degrees laterally, relative to the sagittal plane, and 10 degrees
      to 20 degrees inferiorly, relative to the transverse plane, was found to be the
      best approach to the intra-articular portion of the sacroiliac joint.

PMID- 9181193
TI  - The effect of knee immobilization on degree of hip flexion: a clinical
      correlation with posterior wall acetabular fractures.
AB  - The purpose of this investigation was to determine whether maintaining the knee
      in extension substantially limits hip flexion. The dominant lower extremity in 22
      male subjects was goniometrically evaluated to determine hip flexion both when
      the knee was allowed to flex and when the knee was held in extension. Pelvic
      rotation values were subtracted from thigh rotation values to show true flexion
      of the femur in relation to the pelvis. Hip flexion averaged 49.25 degrees +/-
      9.08 degrees in the straight-leg raise test and 94.14 degrees +/- 4.94 degrees in
      the flexed-knee raise test. This study shows that using a knee immobilizer in the
      postoperative treatment of posterior wall acetabular fractures should serve to
      protect the fracture site while still affording early ambulation.

PMID- 9181194
TI  - Salvage anterior C1-C2 screw fixation and arthrodesis through the lateral
      approach in a patient with a symptomatic pseudoarthrosis.
AB  - On occasions when the posterior approach to the upper cervical spine is not
      feasible, the options provided by a lateral exposure can be invaluable. A case of
      a nonunited posterior fusion between C1 and C2, with a free-floating posterior C1
      arch due to nonhealing of a previous intraoperative C1 ring fracture, is
      presented to illustrate this point. This 28-year-old man underwent screw fixation
      between the first and second cervical vertebrae, supplemented with autogenous
      iliac crest cancellous bone graft, via the lateral approach of Whitesides. The
      patient's symptoms subsequently resolved, and radiographic evaluation 3 months
      after the procedure revealed a solid fusion.

PMID- 9181195
TI  - Pyomyositis of the calf muscles mimicking distal deep venous thrombosis: a case
      report.
AB  - Pyomyositis is a pyogenic infection of skeletal muscle. It is relatively rare in
      temperate climates. Unfamiliarity with the lesion may lead to a delay in
      diagnosis. This report describes pyomyositis of the calf muscles in a patient
      with chronic hepatitis whose clinical symptoms simulated those of distal deep
      venous thrombosis. The correct diagnosis was not made until computed tomography
      revealed a local abscess in the calf muscles.

PMID- 9181197
TI  - Pseudomonas osteomyelitis of the metatarsal sesamoid bones.
AB  - It is unusual for osteomyelitis of the sesamoid bones to occur after a puncture
      wound to the foot. When the puncture occurs through tennis shoes, the risk of
      Pseudomonas infection is increased. Pseudomonas was the causative organism in 7
      of 22 cases reported in the literature. This report will explore the causes and
      natural history, as well as the treatment, of these infections. Initially, basic
      wound care principles should be adhered to when treating these wounds. Patient
      awareness and close follow-up is important to ensure complete healing. Treatment
      of this case involved intravenous antibiotics and medial sesamoidectomy. Foot
      deformities can occur with sesamoid osteomyelitis and sesamoid excision. Hallux
      valgus deformity was noted to occur with the osteomyelitis and worsen with
      sesamoid excision. Preservation of surrounding structures during excision is
      important to prevent deformity.

PMID- 9181196
TI  - Management of infected defect nonunion of the metacarpals.
AB  - A 30-year-old man sustained a displaced closed fracture of the fourth metacarpal
      bone, which was treated by open reduction and internal fixation with Kirschner
      wires. Severe postoperative infection led to a segmental defect with shortening
      of the fourth metacarpal bone and infected defect nonunion of the fifth
      metacarpal bone. After serial debridements and intravenous antibiotics, the
      infection was controlled. An AO external minifixator was applied to restore the
      length of the fourth metacarpal bone and to stabilize the fourth and fifth
      metacarpals, and iliac bone grafting was performed, leading to complete healing
      and restoration of normal hand function.

PMID- 9181198
TI  - Compartment syndrome after isolated perfusion of the leg: a case report.
AB  - The authors present a case of a lower leg compartment syndrome that developed
      after a regional chemotherapy technique was used for recurrent melanoma of the
      foot in a 74-year-old woman. The diagnosis was based on the results of physical
      examination, with confirmation by intracompartmental pressures. Prompt
      consultation of orthopedic surgeons and fasciotomy helped avoid potentially
      crippling sequelae.

PMID- 9181199
TI  - "Krammer splint technique" for immediate measuring of intramedullary nails.
AB  - We illustrate a simple and quick method of measuring the length of the
      intramedullary nail. The method utilizes the intervals between the metal ranks of
      the Krammer splint, and it has proved especially useful in the care of
      multitrauma victims.

PMID- 9181200
TI  - Impact of a one-day antismoking program on male secondary-school adolescents in
      southwestern Saudi Arabia.

PMID- 9181201
TI  - Teaching smoking-cessation counseling to medical students using simulated
      patients.
AB  - OBJECTIVE: Our objective was to evaluate the effectiveness of using simulated
      patient instructors and the Ockene method to instruct third-year medical students
      in smoking-cessation counseling techniques. DESIGN: We used a clinical exercise
      with self-study preparation and simulated patient instructors. METHODS: One
      hundred fifty-nine students participated in a smoking-cessation counseling
      session in which cognitive and behavioral endpoints were assessed by simulated
      patient instructors and the students themselves. RESULTS: Student performance in
      the cognitive and behavioral components of model smoking-cessation counseling was
      acceptable. Specific areas of weakness, such as the tendency of students to
      underemphasize the personal and social benefits of smoking cessation, and to
      overestimate their competence on a number of skill items, were identified.
      Student evaluation of the exercise was positive. CONCLUSIONS: Smoking-cessation
      counseling can be taught effectively to third-year medical students by simulated
      patient instructors during a clinical clerkship.

PMID- 9181202
TI  - Does gender affect response to a brief clinic-based smoking intervention?
AB  - INTRODUCTION: Although recent reviews suggest few gender differences in smoking
      cessation outcomes, it is important to establish whether gender differences exist
      in response to the brief interventions increasingly recommended as part of
      routine medical care. METHODS: We used data from an efficacious primary care
      based smoking intervention to examine gender differences in smoking
      characteristics, use of intervention components, self-reported quitting
      activities, and cessation outcomes among all smokers randomized to receive
      clinician advice and nurse-assisted intervention (n = 1,978, 58% female).
      RESULTS: Although female and male smokers differed on a number of
      sociodemographic and smoking-related characteristics, they were equally likely to
      participate in each step of the recommended intervention. Female and male smokers
      were also equally likely to report quit attempts and cessation at 3, 12, and 3
      and 12 months (combined long-term cessation endpoint). Similarly, no gender
      difference in relapse at 12 months was seen. Women attempting to quit used a
      greater number and variety of smoking-cessation strategies, suggesting that,
      although outcomes were similar, the processes of cessation may vary by gender.
      CONCLUSIONS: Since this brief intervention in primary care was equally
      efficacious and acceptable to female and male smokers, broader implementation in
      medical settings of this population-based approach to reducing tobacco use is
      warranted. Indeed, widespread implementation of smoking-cessation programs in
      medical settings may particularly benefit women, who are more likely than men to
      have contacts with the medical care system.

PMID- 9181203
TI  - Perceived and measured availability of tobacco to youths in 14 Minnesota
      communities: the TPOP Study. Tobacco Policy Options for Prevention.
AB  - INTRODUCTION: Availability of tobacco to young people is believed to be an
      important factor in the onset of tobacco use. We still do not have a complete
      picture of how tobacco is obtained by youths or how access can be curtailed.
      DESIGN: This article describes tobacco availability to youths in 14 communities
      that are part of a randomized trial, known as TPOP (Tobacco Policy Options for
      Prevention). The data reported here were obtained from student surveys and
      tobacco-purchase attempts by underage confederates. RESULTS: Students who have
      smoked at least once were likely to cite social sources for cigarettes. However,
      more than half of weekly smokers and almost one third of tenth-grade ever smokers
      reported purchasing cigarettes in the last 30 days. Tobacco-purchase attempts by
      confederate buyers at all outlets resulted in an overall success rate of 40.8%,
      lower than previously reported for urban communities. Fifty-five percent of the
      over-the-counter outlets had no self-service displays of tobacco at baseline.
      Store factors that predicted purchase success include tobacco location; purchase
      success was lower when all tobacco was locked or behind a service counter. The
      percentage of smokers who reported purchasing their own tobacco soon after
      starting to smoke was highest in towns where purchase success by teenage study
      confederates was highest. CONCLUSIONS: These results suggest that sources of
      cigarettes shift from social to commercial with age and that sources of
      cigarettes for rural youths may be different than for urban youths.

PMID- 9181204
TI  - Cigarette smoking and tuberculin skin test conversion among incarcerated adults.
AB  - INTRODUCTION: The purpose of this case-control study was to determine whether
      smoking plays a role in tuberculin skin test conversion among the inmate
      population of South Carolina. RESULTS: The major findings of this study indicate
      that smokers were more likely to have become tuberculin skin test converters
      during incarceration than nonsmokers (odds ratio [OR] = 1.78, 95% confidence
      intervals [CI = 0.98, 3.21). Inmates who smoked 1 to 20 cigarettes per day prior
      to incarceration (OR = 1.32, 95% CI = 0.76, 2.31), and those who smoked > 20
      cigarettes per day prior to incarceration (OR = 1.75, 95% CI = 0.83, 3.71) were
      more likely to have become converters during incarceration than nonsmokers,
      suggesting a dose-response effect. Converters were found to have reduced their
      number of cigarettes smoked per day since incarceration. Those inmates smoking 1
      to 10 cigarettes per day (OR = 1.88, 95% CI = 0.96, 3.69), and those who smoked >
      10 cigarettes per day since incarceration (OR = 1.87, 95% CI = 0.92, 3.78) were
      more likely to have become converters than nonsmokers. Interestingly, inmates who
      smoked for 15 years or less were more likely to have become tuberculin skin test
      converters than nonsmokers (OR = 1.60, 95% CI = 0.81, 3.16), while those smoking
      for more than 15 years were more likely to have become converters than nonsmokers
      while incarcerated (OR = 2.12, 95% CI = 1.03, 4.36). CONCLUSIONS: This suggests
      that the cumulative effects related to the duration of smoking may be more
      important than the number of cigarettes smoked with regard to tuberculin skin
      test conversion. This is consistent with the understanding that long-term
      exposure to cigarette smoking has an adverse effect on the lung's defense
      mechanisms, namely mucociliary clearance of potential pathogens, such as
      Mycobacterium tuberculosis.

PMID- 9181205
TI  - A strategy for reducing tuberculosis among Oglala Sioux Native Americans.
AB  - BACKGROUND: The Oglala Sioux people, who live on the second largest Native
      American reservation in the United States, the Pine Ridge Reservation in South
      Dakota, have a history of high rates of tuberculosis. METHODS: To determine a
      strategy for reducing tuberculosis in this population, Pine Ridge Reservation
      tuberculosis cases since 1968 were analyzed. Diabetic patients were identified
      through chart reviews and characterized for tuberculosis status. Age-specific
      tuberculosis rates and age-specific relative risks (RRs) were calculated and
      compared with those of South Dakota excluding Pine Ridge. RESULTS: Between 1968
      and 1994, the RR for tuberculosis was 18.9 for a Pine Ridge Native American
      compared with rates for the rest of South Dakota. The age-specific RR was 65.7
      for the Pine Ridge population 65 and older from 1985-1994. Tuberculin tests were
      positive in 70% of diabetic patients on the reservation. Diabetic patients
      comprise 23% of the population 45 and older at Pine Ridge. Fifty-five percent of
      all the tuberculosis disease in the 45 and older age group can be prevented by
      eliminating it in the diabetic population. CONCLUSIONS: A major stride toward
      reducing tuberculosis can be made by targeting high-risk groups such as diabetic
      patients, especially in a time of dwindling resources and personnel for
      tuberculosis control.

PMID- 9181206
TI  - Use of automated reminders for tuberculin skin test return.
AB  - INTRODUCTION: This study assessed the impact of automated telephone reminders on
      tuberculin skin test returns. METHODS: A total of 701 English-speaking and
      Spanish-speaking patients of a public health immunization program were randomly
      assigned to an intervention or a control group. Those in the intervention group
      received an automated telephone reminder to return for the reading of their skin
      test. RESULTS: Automated telephone reminders significantly reduced return
      failures 53% (from 14% to 7%) when the scheduled interval between test
      administration and reading was three days, but had no impact for a two-day
      interval. Effectiveness of reminders did not differ significantly by patient age,
      gender, or language (English versus Spanish). CONCLUSIONS: Results suggest the
      value of automated reminder calls for intra-appointment intervals as short as
      three days.

PMID- 9181207
TI  - Predictors of follow-through on plans to be tested for HIV.
AB  - INTRODUCTION: Fewer than 40% of people in the United States with HIV risk factors
      have been tested. However, almost 40% of untested individuals with HIV risk
      factors in high AIDS prevalence cities stated in the 1991 National AIDS
      Behavioral Surveys (NABS) that they (1) "planned to be tested" or (2) "would get
      tested if no one could find out." METHODS: We used longitudinal data from the
      1991 and 1992 NABS (n = 5,543), which are nationally representative telephone
      surveys. We assessed whether untested individuals were tested one year later, and
      we used logistic regressions to address two research questions: What are the
      predictors of testing among untested individuals? What are the predictors of
      testing among untested individuals who "planned to be tested" or "would get
      tested if no one could find out?" RESULTS: We found that 30% of individuals who
      "planned to be tested," 16% of individuals who "would get tested if no one could
      find out," and 11% of persons with no intentions to be tested had been tested one
      year later (P < .001). In regression analyses, risk factors and higher education
      were key predictors of testing. CONCLUSIONS: It is encouraging that 30% of
      individuals who plan to be tested did get tested within one year. Further
      research, however, needs to examine testing barriers for the 70% of individuals
      who do not follow through on testing plans. The results provide important
      information for targeting testing programs, developing effective public policies,
      and addressing the debate over issues such as name reporting and the availability
      of home HIV tests.

PMID- 9181208
TI  - Predictors of the performance of breast and cervical cancer early detection by
      public health nurses.
AB  - INTRODUCTION: Public health nurses (PHNs) often serve as primary care providers,
      yet few studies have examined their practice patterns in the early detection of
      breast and cervical cancer. METHODS: We conducted a cross-sectional survey of all
      PHNs (N = 1,894) employed by the county health departments of North Carolina in
      July 1993 to describe the predictors of their performance of breast and cervical
      cancer early detection. The main outcome measures were self-report of cancer
      prevention and screening services provided for their adult clients, nursing self
      confidence for counseling clients about cancer prevention, and training
      experience. Self-confidence for counseling clients about cancer prevention was
      measured by asking whether a nurse had sufficient knowledge to educate clients
      about cancer prevention as well as by obtaining nursing perception of the quality
      of their clinical skills. RESULTS: The response rate was 78%. Final sample
      consisted of 1,369 PHNs, after exclusion of 101 nurse practitioners. Nurses
      reported high performance rates of cancer screening, although self-rating of the
      quality of their clinical skills was often low. However, nurses who reported
      having higher quality clinical skills or who reported having sufficient knowledge
      to educate clients were significantly more likely to report a greater frequency
      of performing cancer screening and counseling. This self-confidence and
      performance association was independent of nursing certification to perform
      screening, job classification, education, knowledge, or continuing education
      coursework. CONCLUSIONS: Self-confidence is a significant predictor of PHNs'
      reported performance of cancer screening and counseling. Further studies to
      verify whether self-report predicts actual performance of cancer early detection
      are needed.

PMID- 9181209
TI  - Barriers to breast and cervical cancer screening among Vietnamese-American women.
AB  - INTRODUCTION: We investigated barriers to breast and cervical cancer screening
      among Vietnamese women in San Francisco and Sacramento, California. METHODS: Face
      to-face interviews were conducted in 1992 of 306 Vietnamese women in San
      Francisco and of 339 women in Sacramento. RESULTS: In both communities, only
      about one half of Vietnamese women had ever had routine check-ups, clinical
      breast examinations, mammograms, and Pap smear tests, and only about one third
      were up-to-date for these screening examinations. Among women age 40 or older,
      35% had never even contemplated having a mammogram. This study identified several
      significant barriers to recognition, receipt, and currency of screening tests.
      Negative predictors of test recognition included low level of education and not
      having a regular physician. Negative predictors of test receipt included low
      level of education, not having a regular physician, short duration of residence
      in the United States, and never having been married. A major negative predictor
      of test currency was low level of education. With a few exceptions, attitudes and
      beliefs generally were not important predictors. CONCLUSIONS: Health education
      and screening programs for early breast and cervical cancer detection among
      Vietnamese women must be culturally appropriate and conducted in the Vietnamese
      language. Special outreach efforts are needed to assist recent immigrants in
      obtaining recommended breast and cervical cancer screening examinations.

PMID- 9181210
TI  - Activating patients to practice skin cancer prevention: response to mailed
      materials from physicians versus HMOs.
AB  - OBJECTIVES: We investigated whether the source and emphasis of mailed messages
      about skin cancer would differentially activate patients to initiate skin cancer
      prevention by calling a toll-free number. METHODS: We mailed a questionnaire to
      981 randomly selected patients of a large medical group to assess their concern
      about and risk for skin cancer: 48 were returned undeliverable (n = 933). The
      booklet was accompanied by a letter inviting patients to call a toll-free number.
      Patients received the letter from one of three sources: (1) their physician, (2)
      their HMO, or (3) a fictitious junk mail organization. Patients received one of
      three different messages emphasizing the effects of ultraviolet (UV) rays on (1)
      the risk of skin cancer, (2) aging and wrinkling of the skin, or (3) aging and
      wrinkling accompanied by a book further emphasizing these harmful effects of the
      sun. RESULTS: The overall activation rate was low (7%); nevertheless, the source
      of the preventive message significantly affected whether patients called in.
      Messages from physicians and HMOs were more activating than messages from the
      junk mail organization (odds ratio [OR] = 3.40, confidence intervals [CI] = 1.66,
      6.97), but messages from physicians were not more activating than messages from
      HMOs (OR = 1.56, CI = .90, 2.72). The emphasis of the message did not
      significantly affect call-in rates. Risk for skin cancer was positively
      associated with patient activation, but attitudes and beliefs about skin cancer
      prevention were unrelated to activation. CONCLUSIONS: These results should
      encourage HMOs and physicians to continue their preventive health outreach as one
      aspect of multicomponent prevention efforts. The results also suggest that HMOs
      and physicians can activate patients most at risk for skin cancer by emphasizing
      both risks of cancer and aging and wrinkling when they deliver a skin cancer
      preventive message.

PMID- 9181211
TI  - Neonatal chlamydial infections in Massachusetts, 1992-1993.
AB  - INTRODUCTION: An increase in the numbers of babies reported with Chlamydia
      trachomatis infections in Massachusetts prompted a review of the medical records
      of both infants and mothers to evaluate the clinical presentation, the maternal
      epidemiologic profile, risks of transmission, and the screening practices of
      health care providers. METHODS: Medical records of 44/47 infants reported with a
      chlamydial infection in 1992-1993 were analyzed, as were 40 of the maternal
      records. RESULTS: Almost all of the infants (39, or 89%) had conjunctivitis,
      despite the fact that ocular prophylaxis with erythromycin was documented at
      birth for 34 infants. Five other infants presented with respiratory tract
      infections without conjunctivitis, and they had all received prophylaxis at birth
      either with erythromycin (3) or silver nitrate instillation (2). More than one
      fifth (10, or 22.7%) had a respiratory tract infection. Seventy percent of the
      mothers were younger than 25. More than 85% were receiving prenatal care by the
      end of the second trimester. Twenty-five (62.5%) were screened for chlamydia.
      Nine women tested positive, seven of whom were tested beyond the first trimester.
      Seventy-five percent of the women who tested negative were tested in the first
      trimester. DISCUSSION: This case series supports previous data documenting that
      ocular prophylaxis can fail to prevent neonatal chlamydial conjunctivitis, and
      does not prevent colonization or infection at other sites. This study reinforces
      the importance of primary prevention of neonatal infections through prenatal
      screening in the third trimester, treatment of infected mothers and their sexual
      partner(s), and active follow-up.

PMID- 9181212
TI  - Immediate breast reconstruction. A review.
AB  - In summary, immediate breast reconstruction has many advantages to the patients
      and to the surgeons who perform breast reconstruction. For the patients, it is
      less expensive, psychologically easier, and more convenient. For the surgeons, it
      facilitates the reconstruction and improves the aesthetic results. Oncologically,
      there is no reason not to perform immediate breast reconstruction unless the
      patient does not want it or the prognosis is so poor that any breast
      reconstruction is unwarranted. We generally offer immediate breast reconstruction
      to all patients with in situ, T1, or T2 breast cancers who are appropriate
      surgical candidates. We also offer it to selected patients with T3 breast cancers
      if the patients are good surgical candidates and are anxious to undergo immediate
      reconstruction. Skin-sparing mastectomy combined with immediate breast
      reconstruction has improved the quality of our results and the quality of our
      patients' lives. By helping our patients in this manner, it has increased the
      amount of pride we can take in our work and therefore the quality of our own
      lives as well.

PMID- 9181213
TI  - Poor prognosis of gallbladder cancer persists regardless of improved diagnostic
      methods. Incidence and results of surgery during 20 years in Helsinki.
AB  - BACKGROUND AND AIMS: The ominous prognosis of primary gallbladder cancer is well
      known. This study assesses whether the prognosis has improved, and whether the
      substantial development in the radiologic imaging techniques is reflected in the
      survival of these patients. MATERIAL AND METHODS: The series consisted of 122
      patients operated on for primary cancer in the gallbladder in the Helsinki City
      area between 1970 and 1990. RESULTS: The mean age of the patients was 68.6 years
      and did not change during the period, but there was a significant proportional
      increase in male patients. Only 2% of patients had a localized disease at the
      time of diagnosis, and there was no improvement in the diagnostic sensitivity
      during the observation period. Yet, the number of unexpected postoperative cancer
      diagnoses increased from 4% to 15% during the two decades. The primary mortality
      decreased from 21% to 13%, the one-year survival increased from 7% to 13%,
      whereas the five-year survival remained unchanged. CONCLUSIONS: During the past
      two decades the frequency of surgery for primary gallbladder cancer has increased
      significantly among males in the Helsinki City area. Regardless of the improved
      immediate survival the long-term survival has remained poor. The marked
      development in radiologic techniques is not reflected in the prognosis of these
      patients. Even under conditions in which the potential for the diagnosis of a
      malignant gallbladder disease is available, the opportunities for radical surgery
      are not utilized maximally, which is a cause for concern.

PMID- 9181214
TI  - Laparoscopy aided gastrostomy in children.
AB  - BACKGROUND AND AIMS: The aim of this report is to describe a method for
      laparoscopy aided button gastrostomy in children. MATERIAL AND METHODS: The
      method includes the use of two ports, one umbilical and one subcostal on the left
      side. The stomach is exteriorized using a grasping forceps in the subcostal port.
      Under direct vision the gastrostomy button, MIC-KEY, is inserted into the stomach
      at the lesser curvature and secured by purse string sutures. The stomach is
      attached to the anterior abdominal wall. RESULTS: The results show that this
      method has been successfully used in 33 children without operative complications.
      CONCLUSIONS: We conclude that by inserting the gastrostomy button under direct
      vision, damage to other abdominal organs is avoided and a correct placement at
      the lesser curvature obtained. The combination of laparoscopic and open
      procedures makes the method easy and safe.

PMID- 9181215
TI  - The rupture type determines the outcome for ruptured abdominal aortic aneurysm
      patients.
AB  - BACKGROUND: The treatment of patients with ruptured abdominal aortic aneurysm
      (RAAA) poses a significant surgical challenge. To achieve improvement in
      survival, factors influencing case fatality must be identified and modified. The
      aim of the present survey was to determine the contribution of preoperative,
      perioperative and postoperative events in predicting the mortality among AAA
      patients undergoing an emergency operation. MATERIAL AND METHODS: Fifty-one
      consecutive patients with ruptured infrarenal abdominal aortic aneurysm and
      twenty-six patients with 'expanding symptomatic aneurysms' (EAAA) were reviewed
      retrospectively to determine the relative contributions of preoperative,
      perioperative and postoperative factors on mortality. RESULTS AND CONCLUSIONS:
      The 30-day mortality was 47% in the RAAA group and 12% in the EAAA group. The
      rupture type was the main predictor of the outcome for the RAAA patients, the
      mortalities being 88% and 29% among patients with free (n = 16) and contained (n
      = 35) ruptures, respectively. In conclusion, the best way of avoiding poor
      results in cases of emergency aneurysm repair is to aim at elective operations.
      After the rupture, the clinical course is mainly determined by the rupture type,
      which is unfortunately beyond the surgeon's control. Surgical expertise and the
      avoidance of technical error can significantly affect the survival.

PMID- 9181216
TI  - The role of bronchoplasty in the treatment of lung cancer.
AB  - Over a half of the patients with lung cancer have inoperable disease on
      diagnosis. Limited respiratory reserve due to chronic pulmonary disease can
      preclude patients from pneumonectomy. A bronchoplastic resection can be used to
      circumvent pneumonectomy in selected cases. Its applicability in lung cancer was
      investigated by following up a total of 28 patients who underwent this procedure
      for lung cancer between 1973 and 1993 in our institution. This was only
      approximately 1.4% of all our lung cancer operations. The actuarial five-year
      survival probability was 40%, and the complication rate was 16%. These values are
      comparable to those reported in the literature and to those of pneumonectomy. It
      appears that the ideal cases with a proximal tumour but limited disease are rare.

PMID- 9181217
TI  - Is varicocele treatment useful?
AB  - The effect of the treatment of varicocele on symptoms and fertility was followed
      up in 66 patients for an average of 27 months (range 6-84 months). The patients
      had been treated either surgically (n = 45) or with embolization (n = 21). The
      mean duration of the inpatient periods and sick leaves were significantly shorter
      among the patients treated with embolization than among the surgical patients
      (2.4 vs 3.3 days and 4.8 vs 21.3 days, respectively). Scrotal problems
      disappeared either completely or almost completely in 73% of the patients treated
      for symptoms (n = 40). The number of spermatozoa increased significantly (from
      6.7 mill/ml to 27.4 mill/ml) in the patients with infertility after the treatment
      of varicocele. Pregnancy started in 31% of the couples with infertility problems.
      A spontaneous abortion occurred in two cases, and six couples (23%) had a child
      of their own. It could be concluded that the treatment of varicocele is useful
      regardless of whether it is given for symptoms or infertility. It is also
      indicated for the patients with infertility problems who have a low number of
      spermatozoa and disturbed spermatozoan motility in sperm analysis.

PMID- 9181218
TI  - Fibrosis in the subacromial bursa and outcome after acromioplasty.
AB  - BACKGROUND AND AIMS: The subacromial bursa tends to undergo proliferative or
      degenerative changes in patients with impingement syndrome. The aim of the study
      was to quantify the degree of fibrosis in the subacromial bursa in context with
      the outcome after acromioplasty. MATERIAL AND METHODS: Twenty-one patients with
      impingement syndrome underwent acromioplasty, and in each case biopsies from the
      subacromial bursa were taken. Fibrosis in the subacromial bursa was assessed
      histologically with van Gieson staining technique, and a three-graded scale was
      used. Five normal shoulders from an autopsy series served as controls. RESULTS
      AND CONCLUSIONS: Ten patients had severe fibrosis, eight had moderate fibrosis
      and one patient had no fibrosis at all. All normal controls had no fibrosis. The
      postoperative outcome seemed to be more favourable in patients with severe
      fibrosis (7 out of 10) contrary to patients with moderate fibrosis of whom only
      three out of eight were graded as a success. The outcome of acromioplasty in
      patients with impingement was clearly dependent on the degree of fibrosis in the
      subacromial bursa.

PMID- 9181219
TI  - Bone mineral density in fractures treated with absorbable or metallic implants.
AB  - Absorbable fixation devices have been clinically used in the fracture treatment
      for over ten years. No studies have been published where bone mineral density has
      been measured after bone consolidation comparing absorbable and metallic
      fixation. In this study the bone mineral density was measured after operative
      ankle fracture treatment with absorbable self-reinforced polyglycolic acid (SR
      PGA) screws (14 patients) or with absorbable self-reinforced polylactic acid (SR
      PLLA) screws (eight patients) compared with metallic fixation (17 patients). The
      overall results were radiologically good in every group. A statistically
      significant difference in the bone mineral density (BMD) was found only in the
      distal tibial metaphysis between SR-PGA screw and metallic fixation. The BMD
      increased in the distal tibia after SR-PGA screw fixation by an average 18.3%.
      The average change of BMD in the distal tibia after SR-PLLA screw fixation
      decreased by 6.4% while after metallic fixation the average change of MBD
      decreased by 18.6%. Bone mineral density measurements in the present study may
      indicate osteogenetic capacity of polyglycolide implants in the bone after
      fracture or osteotomy fixation. On the other hand, metallic implants showed
      negative effects to the bone.

PMID- 9181220
TI  - Malunion after intramedullary nailing of tibial shaft fractures.
AB  - BACKGROUND AND AIMS: The purpose of the study was to find out the consequences of
      malunion of tibial shaft fracture. PATIENTS AND METHODS: Sixty-four fractures
      were treated using an intramedullary nail or an intramedullary compression nail.
      Malunion was defined as an angular or rotational deformity exceeding five degrees
      or a shortening exceeding 10 mm. RESULTS: The number of malunited fractures was
      17. The main reason for malunion was a technical failure occurring in 11
      fractures. Patients with malunion had on average twice as many pathological
      functional findings as patients with sound union (P < 0.05). The mean number of
      subjective complaints was 5.3 in the malunion group and 3.3 in the sound union
      group. Among patients less than 45 years of age, those with malunited fractures
      had to reduce or give up physical exercise more often than those with fractures
      with sound union (P < 0.05). CONCLUSION: Malunion of tibial shaft fracture seems
      to be especially harmful in distal fractures, in fractures with marked primary
      displacement, in fractures caused by high energy injury, and among patients less
      than 45 years of age.

PMID- 9181221
TI  - Absorbable polylactide pins versus metallic Kirschner wires in the fixation of
      cancellous bone osteotomies in rats.
AB  - A transverse transcondylar osteotomy of the distal femur was fixed with
      biodegradable self-reinforced polylevolactide (SR-PLLA) pin in 42 rats and with
      metallic Kirschner wire in 42 rats. Consolidation of the osteotomy and periosteal
      callus formation was examined within standardised sample fields histologically,
      histomorphometrically and microradiographically one week, 3, 6, 12, 24, 36 and 48
      weeks postoperatively. The intact contralateral femur served as control. From 3
      week to 48-week follow-up time the total trabecular bone area of the SR-PLLA
      group at the osteotomy site was significantly larger in the operated femora than
      in the intact control femora at the corresponding site. The specimens of the
      Kirschner wire group showed significantly larger total bone area only at 12 weeks
      postoperatively as compared with the nonoperated femora. In the SR-PLLA group 28
      and in the metallic group 31 osteotomies showed solid bony union. In both
      experimental groups the osteotomies with solid bony union showed only scantly
      periosteal callus formation. More abundant callus formation in both experimental
      groups was related to incomplete union of the osteotomy. No signs of degradation
      of the SR-PLLA implant could be noticed within the follow-up times of this study.
      Only mild foreign body reaction to both SR-PLLA pins and metallic Kirschner wires
      was observed during the observation period. The fixation properties of both SR
      PLLA pins and metallic Kirschner wires seem to be sufficient for the fixation of
      small cancellous bone fragments, but by using SR-PLLA pins instead of Kirschner
      wires subsequent second operation for removal of the implants can be avoided.

PMID- 9181222
TI  - Haemorrhage into a duodenal cyst with ectopic gastric epithelium, a rare cause of
      gastric outlet obstruction in an adult.
AB  - BACKGROUND: Duodenal duplications, including also cysts with gastric epithelium,
      are congenital anomalies observed in less than 1 per 100,000 births. They are
      usually detected in infants or children. AIM: To evaluate and discuss the
      diagnostic work-up and treatment. MATERIAL AND METHODS: A rare case of
      haemorrhage in the duodenal cyst in a 32-year-old woman with gastric outlet
      obstruction is presented. RESULTS: Computed tomography (CT) revealed cystic
      lesion in the duodenum. Endoscopic retrograde cholangiopancreatography (ERCP)
      showed normal biliary and pancreatic ducts. Final histology demonstrated cystic
      lesion in the duodenum which was lined with gastric mucosa. CONCLUSION:
      Preoperative CT and ERCP are important in the differential diagnosis and planning
      of treatment in duodenal cystic lesions.

PMID- 9181223
TI  - Anomalous nerve anatomy at the wrist?
AB  - BACKGROUND AND AIMS: The common course of the ulnar and median nerve in the
      carpal tunnel has been described previously on two occasions. The aim of the
      study was to explain the cause of two main nerve trunks in the carpal tunnel
      found at an operation. MATERIAL AND METHODS: A patient was treated with open
      reduction and internal fixation for a volar Barton's fracture of the distal
      radius. Later, compression syndrome of the ulnar and median nerves developed. At
      operation, two nerves were found in the carpal tunnel. Electroneuromyography
      (ENMG) and magnetic resonance imaging (MRI) confirmed a divided median nerve.
      RESULT AND CONCLUSION: No anomaly of the ulnar nerve was confirmed. Deviation
      from the common clinical and ENMG picture of the carpal tunnel syndrome should
      result in thorough evaluation of possible anomalous nerve anatomy at the wrist.
      When at operation findings are suspicious of anomalous anatomy of the median or
      ulnar nerves in the carpal tunnel, Guyon's canal should also be explored to
      clarify the anatomy of the nerves. In cases with previous carpal collapse or
      other space occupying lesions we recommend division of the whole transverse
      carpal ligament in connection with a volar osteosynthesis, because the operative
      trauma may cause elevation of pressure in both the carpal and Guyon's canals.

PMID- 9181224
TI  - Fibromatosis of the female pelvis.
AB  - BACKGROUND AND AIMS: Desmoid tumour is a rare entity characterized by benign
      proliferation of fibroblasts. Although non malignant, this tumour can be life
      threatening due to its invasive property and high recurrence rate. MATERIAL AND
      METHODS: We report a case of pelvic fibromatosis whereby the tumour was
      completely resected without sacrificing organs or major vessels. RESULTS: Thirty
      months after surgery the patient is asymptomatic, without any sign of recurrent
      disease. CONCLUSIONS: Radical surgery represents the main primary treatment for
      pelvic fibromatosis. The other available therapeutic options are discussed.

PMID- 9181225
TI  - Appropriate management of atypical ductal hyperplasia diagnosed by stereotactic
      core needle breast biopsy.
AB  - BACKGROUND: Stereotactic core needle breast biopsy (SCNBB) is a minimally
      invasive technique used to sample nonpalpable mammographic abnormalities. The
      optimal management of atypical ductal hyperplasia (ADH) diagnosed by SCNBB is
      unknown. We hypothesized that ADH diagnosed by SCNBB should be evaluated by
      excisional breast biopsy (EBB) because of the risk of identifying carcinoma in
      association with ADH that would be missed if a diagnostic sampling technique
      alone was utilized. METHODS: To test this hypothesis, a prospective diagnostic
      protocol was created which called for SCNBB instead of EBB for patients with
      mammographic abnormalities considered suspicious for malignancy. If ADH was noted
      on histologic evaluation of the cores, patients were advised to undergo an EBB.
      RESULTS: A review of the initial 900 patients evaluated by SCNBB yielded 39
      patients (4.3%) with ADH detected by SCNBB. Thirty-six of these 39 patients
      agreed to proceed with EBB: 19 patients demonstrated benign findings including
      atypical ductal hyperplasia, 13 patients demonstrated noninvasive ductal
      carcinoma, and 4 patients had evidence of invasive carcinoma. CONCLUSIONS: A 47%
      rate of detecting noninvasive or invasive breast carcinoma supports the
      hypothesis that ADH detected by a sampling technique, such as SCNBB, should be
      managed by EBB.

PMID- 9181226
TI  - Underlying pathology in mammary Paget's disease.
AB  - BACKGROUND: Management of patients with mammary Paget's disease is controversial;
      recent recommendations range from primary radiotherapy to modified radical
      mastectomy. This review correlates associated breast findings with disease stage
      and outcome to help guide evaluation and treatment. METHODS: Retrospective review
      of clinical, mammographic and pathologic data from 38 women with mammary Paget's
      disease treated between 1979 and 1995 was performed. Mastectomies were performed
      on all but two patients with the entire breast and lymph nodes evaluated for
      histopathologic evidence of carcinoma. RESULTS: Underlying carcinoma (ductal
      carcinoma in situ and/or invasive ductal cancer) was found in most patients (92%)
      even when no palpable mass was evident (85%); this carcinoma is often multifocal
      (73%). Mammography fails to identify the underlying disease in many patients with
      no palpable mass and multifocal underlying disease (64%). Patients with Paget's
      disease and a palpable mass have a much greater incidence of invasive cancer,
      multifocal lesions, and positive lymph nodes, and have worse survival.
      CONCLUSIONS: Although some patients with Paget's disease might be well treated by
      breast conservation therapy, many patients have underlying multifocal carcinoma
      (including invasive cancer), which can be inapparent by examination and
      mammography. Selecting candidates with disease amenable to complete excision
      without mastectomy is problematic.

PMID- 9181227
TI  - Delayed shoulder exercises in reducing seroma frequency after modified radical
      mastectomy: a prospective randomized study.
AB  - BACKGROUND: Seromas and impaired shoulder function are well-known complications
      after modified radical mastectomy for breast cancer. Early postoperative
      physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of
      this study was to evaluate if the frequency of postoperative seromas could be
      reduced, without increasing shoulder dysfunction, by delayed postoperative
      shoulder exercises. METHODS: In a prospective study 163 patients with breast
      cancer undergoing modified radical mastectomy were randomized to physiotherapy
      starting on postoperative day 1 or day 7. Patients were seen by the surgeons and
      the physiotherapists during hospital stay and in the outpatient department.
      Seromas and other complications were registered by the surgeons. The
      physiotherapists instructed the patients pre- and postoperatively and assessed
      shoulder function. RESULTS: There was a significantly higher incidence of
      postoperative seromas in the group of patients that started physiotherapy
      postoperative day 1 (38%) compared to the group that started physiotherapy
      postoperative day 7 (22%) (p < 0.05). There was no significant difference between
      the groups in the late outcome of shoulder function. CONCLUSION: The incidence of
      seromas after modified radical mastectomy for breast cancer is reduced by
      delaying shoulder exercises one week postoperatively. Earlier postoperative
      physiotherapy is not necessary to avoid impaired shoulder function.

PMID- 9181228
TI  - Forequarter amputation with fasciocutaneous deltoid flap reconstruction for
      malignant tumors of the upper extremity.
AB  - BACKGROUND: Malignant tumors of the upper extremity involving a considerable
      portion of the medial axillary wall may require forequarter amputation to achieve
      gross resection of tumor. These resections frequently leave a large defect, often
      requiring a split thickness skin graft or free flap to close the wound. To
      address this problem of wound closure, we have modified our technique and devised
      a reconstructive component as part of our forequarter amputation procedure.
      METHODS: The medical records of seven patients who underwent forequarter
      amputation and fasciocutaneous deltoid flap reconstruction between 1982 and 1994
      were reviewed. RESULTS: All the amputation sites were completely closed with a
      fasciocutaneous deltoid flap without the use of additional skin grafts or free
      flaps. After a median follow-up of 12 months, there were no local recurrences.
      Three patients (43%) are alive and disease free 5, 12, and 19 months after their
      forequarter amputation. One patient is alive with disease after 14 months. The
      remaining three patients died of their disease. CONCLUSION: The fasciocutaneous
      deltoid flap is technically easy to perform, provides wound coverage without the
      use of skin grafts, and is especially useful for tumors involving the media
      axillary wall and in patients with previous axillary radiation.

PMID- 9181229
TI  - Elevation of glutathione and related enzyme activities in high-grade and
      metastatic extremity soft tissue sarcoma.
AB  - BACKGROUND: Glutathione is a free radical scavenger implicated in the
      chemoresistance of certain tumors. As treatment with chemotherapy has added
      little to improved survival in adult soft tissue sarcoma and little is known
      concerning the mechanisms of chemoresistance in sarcoma, we studied
      concentrations of glutathione (nmol/mg protein) and activities of gamma
      glutamylcysteine synthetase (GCS; nmol/mg protein/h) and gamma-glutamyl
      transpeptidase (GGTP; U/mg protein) in extremity soft tissue sarcoma. METHODS AND
      RESULTS: Tumor specimens (n = 65) were frozen in liquid nitrogen at the time of
      resection. Fourteen low-grade tumors, 40 high-grade tumors, and 11 pulmonary
      metastases were analyzed. Glutathione concentrations and GGTP activity were
      significantly lower in low-grade (3.97 +/- 0.7 nmol/mg protein and 1.07 +/- 0.2
      U/mg protein) than in high-grade (8.98 +/- 1.2 nmol/mg protein, p < 0.001; 2.10
      +/- 0.4 U/mg protein, p < 0.002) tumors and pulmonary metastases (10.05 +/- 1.8
      nmol/mg protein, p < 0.008; 3.14 +/- 2.8 U/mg protein, p < 0.04). While GCS
      activity was lower in low-grade (0.81 +/- 0.3 nmol/mg protein/h) than high-grade
      (1.49 +/- 0.5 nmol/mg protein/h) tumors and pulmonary metastases (1.03 +/- 0.2
      nmol/mg protein/h), these differences were not significant. In those patients
      with a high-grade tumor presenting with a local recurrence, glutathione levels
      were higher in those patients who had received preoperative doxorubicin-based
      chemotherapy (9.25 +/- 1.7 nmol/mg protein; n = 7) than in those who had no
      preoperative chemotherapy (4.71 +/- 3.1 nmol/mg protein; n = 4, p = 0.08).
      CONCLUSIONS: In extremity soft tissue sarcoma, glutathione concentration and GGTP
      activity are significantly elevated in patients with high-grade and metastatic
      sarcomas. In addition, there is a trend for increased glutathione levels in
      tumors previously exposed to doxorubicin-based chemotherapy. Glutathione may play
      a role in soft tissue sarcoma chemoresistance.

PMID- 9181230
TI  - Microsatellite instability in breast cancer.
AB  - BACKGROUND: Microsatellites are short repetitive nucleotide sequences that,
      through mutation, can undergo either expansion or contraction. This novel
      mutational mechanism known as microsatellite instability may play a role in
      carcinogenesis. We investigated the incidence of microsatellite instability in a
      series of primary breast carcinoma surgical specimens. METHODS: Using polymerase
      chain reaction techniques followed by polyacrylamide/urea gel electrophoresis, we
      analyzed 46 pairs of normal and primary breast tumor samples at seven different
      microsatellite loci, five of which were located on chromosome 17. RESULTS:
      Thirteen of our 46 tumors (28.2%) demonstrated microsatellite instability. Five
      tumors (10.8%) were unstable at two or more loci, and of those, four (8.7%) were
      unstable at different loci on different chromosomes. An additional five tumors
      demonstrated loss of heterozygosity alone when compared with their normal
      counterparts. CONCLUSIONS: These findings indicate that microsatellite
      instability is present in primary breast cancer populations and, although the
      mechanism of action has yet to be elucidated, may play a role in breast
      carcinogenesis.

PMID- 9181231
TI  - Comparison of histologic diagnosis between stereotactic core needle biopsy and
      open surgical biopsy.
AB  - BACKGROUND: This study correlates the histologic findings of stereotactic core
      needle biopsy (SCNB) with open surgical biopsy (OSB) and identifies which lesions
      can be treated definitively based only on the SCNB histology. METHODS: Women who
      underwent SCNB between July 1, 1993, and January 1, 1969, were identified by
      retrospective chart review. Mammographic (MGM) lesions found by SCNB to be ductal
      or lobular hyperplasia with atypia, or carcinoma underwent OSB. When the
      histologic findings by SCNB were inconsistent with the MGM findings, the lesion
      also underwent OSB. RESULTS: 799 women underwent SCNB with 96 (12%) of these
      going on to OSB. MGM findings in the 92 who presented without a palpable mass
      included microcalcifications (MCS) in 39, mass in 47, MCS and mass in 7, and
      tissue distortion in 3. One hundred one breast lesions biopsied first by SCNB,
      then by OSB were correlated histologically. Sensitivity of SCNB is 89%, with a
      specificity of 94%. Eight-four women (88%) were able to have definitive treatment
      at time of OSB because of prior SCNB, and 703/799 (88%) of women were spared OSB
      entirely. CONCLUSION: SCNB accurately identifies benign breast histology and
      invasive cancers in women with MGM abnormalities, a distinct advantage over fine
      needle aspiration cytology. SCNB does not reliably identify women with DCIS and
      invasion. All women with SCNB diagnosis of ductal or lobular atypia should also
      undergo OSB.

PMID- 9181232
TI  - Importance of a new tumor marker TRA-1-60 in the follow-up of patients with
      clinical stage I nonseminomatous testicular germ cell tumors.
AB  - BACKGROUND: TRA-1-60 is a new tumor marker for embryonal carcinoma-positive
      nonseminomatous testicular germ cell tumors (NSTGCT). Upper normal reference
      value (RV) and serum half-life (t1/2) were determined. The value was determined
      in the follow-up of 154 patients with stage I NSTGCT. METHODS: TRA-1-60 was
      measured in normal controls (n = 100) to determine RV and in patients without
      recurrence for t1/2. In all patients, TRA-1-60 was determined at the time of
      orchidectomy. In 42 patients with recurrence, values were also evaluated 1 month
      before and at the time of computed tomography-confirmed recurrence. Predictive
      values and survival probability were examined and compared with values for alpha
      fetoprotein (AFP) and human chorionic gonadotropin (hCG). RESULTS: RV was 230
      U/ml and t1/2 9.5 days. Elevated TRA-1-60 at the time of orchidectomy was not
      associated with recurrence. One month before recurrence, 21 of 42 patients had
      elevated TRA-1-60 levels (50%); 10 were negative for both AFP and hCG. At the
      time of recurrence, 24 patients had elevated TRA-1-60 levels (57.1%): 9 were
      negative for AFP/hCG. Patients with TRA-1-60 levels of > 500 U/ml had a poorer
      recurrence-free survival probability (p = 0.015). CONCLUSIONS: TRA-1-60 is useful
      in the follow-up of stage 1 NSTGCT. The combination of AFP, hCG, and TRA-1-60 may
      improve the early detection of recurrence.

PMID- 9181233
TI  - Low-risk differentiated thyroid cancer: the need for selective treatment.
AB  - BACKGROUND: The well recognized prognostic factors in differentiated carcinoma of
      the thyroid are age, grade, extracapsular extension, distant metastasis, and size
      of the tumor. Based on these prognostic factors, we have divided patients into
      low-, intermediate-, and high-risk categories. Clearly, there are significant
      differences in these three groups. This article analyzes in depth our data on low
      risk thyroid cancer patients. METHODS: A retrospective review of 1,038 patients
      with differentiated carcinoma of the thyroid was undertaken. Various prognostic
      factors and risk groups were analyzed. Univariate and multivariate analyses were
      performed, and the survival curves were plotted by the Kaplan-Meier method. The
      inclusion criteria for the low-risk group were age younger than 45 years, tumors
      < 4 cm in size, low-grade histology, absence of distant metastasis, and absence
      of extrathyroidal extension. There were 465 patients in the low-risk group. Four
      hundred three patients had papillary and 62 patients had follicular thyroid
      cancer. There were 120 male and 354 female patients. Two hundred seventy-eight
      patients (60%) presented with clinically apparent lymph node metastasis. RESULTS:
      With a median follow-up of 20 years, the 10- and 20-year survival in this select
      group was 99%. The local, regional, and distant recurrence rates were 5, 9, and
      2% in this series. The analysis of the data showed statistical difference in
      local recurrence rate between partial lobectomy and total lobectomy (27 vs. 4%; p
      = 0.005). There was no statistical difference in local recurrence rate between
      total lobectomy compared with total thyroidectomy (4 vs. 1%; p = 0.10). The
      overall failure rate between partial lobectomy and total thyroidectomy (27 vs.
      8%) was statistically significant (p = 0.04). There was no statistical difference
      in the overall failure rate between total lobectomy and total thyroidectomy (13
      vs. 8%; p = 0.06). There was no survival difference between various histologies
      or nodal status. CONCLUSIONS: Patients with low-risk tumors have excellent long
      term survival. Nodulectomy or partial lobectomy should be avoided. The
      intraoperative decisions regarding the extent of thyroidectomy should be based on
      gross clinical findings and risk group analysis.

PMID- 9181234
TI  - Sensitizing T-lymphocytes for adoptive immunotherapy by vaccination with wild
      type or cytokine gene-transduced melanoma.
AB  - BACKGROUND: For the relatively nonimmunogenic B16-F10 murine melanoma, it has
      been found that genetically engineered expression of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) but not interleukin (IL)-2, IL-4, or
      interferon-gamma (IFN-gamma) resulted in a vaccine that could induce resistance
      to rechallenge. Because T cells from lymph nodes draining the sites of some
      progressive tumors can mediate tumor regression after in vitro activation, it
      seemed possible that even apparently nonimmunogenic melanoma cells might induce
      similar preeffector cells in the vaccine-draining lymph nodes (DLNs). METHODS:
      C57BL/6 mice were vaccinated with B16-F10 cells that were either unmodified or
      genetically modified to produce IL-2, IL-4, GM-CSF, or IFN-gamma. DLNs were
      harvested 10 days after vaccination for adoptive immunotherapy (AIT). The DLN
      cells were activated with bryostatin 1 and ionomycin (B/I), expanded for 10 days
      in culture, and transferred to mice with 3-day pulmonary metastases. Pulmonary
      nodules were counted 14 days after AIT. RESULTS: Adoptive transfer of expanded
      DLN lymphocytes sensitized by inoculation of WT B16-F10, or IL-4, GM-CSF, or IFN
      gamma expressing cells significantly reduced pulmonary metastases. Despite the
      spontaneous regression of IL-2-transduced B16-F10 tumors, DLN from mice
      inoculated with IL-2 producing B16 cells had little or no antitumor activity.
      CONCLUSIONS: B16-F10 vaccination strategies that apparently do not induce
      systemic immunity can effectively sensitize DLN preeffector cells.

PMID- 9181235
TI  - Cisplatin-based chemotherapy changes the incidence of bilateral testicular
      cancer.
AB  - BACKGROUND: The introduction of cisplatin-based chemotherapy has remarkably
      increased the survival of testicular cancer patients. With this success, the
      concern for a contralateral testicular tumor has increased. The aim of this study
      was to investigate whether the risk for contralateral testicular tumor
      development was influenced by cisplatin-based chemotherapy. METHODS: The
      incidence of a contralateral testicular tumor among 365 consecutive patients with
      a nonseminoma testicular tumor, diagnosed in the period 1980 and 1995, was
      established and related to previous therapy. RESULTS: Eleven of 365 men (3%)
      developed a contralateral testicular tumor. After a total of 2403 person-years at
      risk, 4 of 225 chemotherapy-treated patients (1.8%) developed a contralateral
      testicular tumor, and 7 of 140 patients (5%) treated with orchidectomy alone
      developed a contralateral tumor. In comparison to this surveillance subgroup,
      patients previously treated with chemotherapy have a relative risk of 0.30 to
      develop a second testicular tumor. CONCLUSIONS: In Dutch men with a nonseminoma
      testicular tumor, the incidence of a contralateral testicular tumor is 3%, which
      is 60-fold the expected incidence rate of testicular cancer. A three times lower
      incidence rate of a contralateral testicular tumor was found in the chemotherapy
      subgroup compared with those on surveillance. This supports the hypothesis that
      cisplatin-based chemotherapy may eradicate carcinoma in situ or early testicular
      cancer.

PMID- 9181236
TI  - Second-look laparotomy in advanced ovarian cancer: a critical assessment of
      morbidity and impact on survival.
AB  - BACKGROUND: The routine inclusion of second-look laparotomy in the management of
      patients with epithelial ovarian cancer is controversial. At issue is the
      justification of morbidity incumbent upon surgery and the possible survival
      benefit of secondary cytoreduction. METHODS: The rate of major complications of
      surgery was assessed among 100 consecutive patients with FIGO stage III or IV
      epithelial ovarian cancer who underwent second-look laparotomy. All patients
      demonstrated a complete clinical and biochemical (CA125 < 35 U/ml) response to
      first-line therapy. Patients were stratified based on findings at surgery.
      Patients in group 1 (n = 37) had a negative second-look laparotomy. Patients in
      group 2 (n = 35) had only microscopically appreciable disease. Patients in group
      3 (n = 28) had macroscopic disease. Cytoreductive efforts aimed at resection of
      all macroscopic disease were carried out for patients in group 3. RESULTS:
      Thirteen patients (13%) had 15 major complications at surgery. Comparison of the
      complication rates for patients in groups 1, 2, and 3, of 10%, 8.5%, and 21.4%,
      respectively, did not achieve statistical significance (p = 0.228). The estimated
      5-year survival for patients in groups 1, 2, and 3 of 63.9%, 39.8%, and 14.2%,
      did differ significantly (p < 0.0001). Cytoreductive efforts resulted in the
      resection of all macroscopic disease in 18 of 28 patients (64.2%) in group 3. The
      median survival for this group of 18 patients was 33 months, and estimated 5-year
      survival was 20%. These values do not differ significantly from those observed
      for patients in group 2. CONCLUSION: The major complication rate associated with
      second-look laparotomy is not prohibitive Secondary cytoreductive efforts may
      result in improved survival for patients with epithelial ovarian cancer.

PMID- 9181237
TI  - A comparison of locoregional depot and systemic preparations of 9
      aminocamptothecin for treatment of liver metastases in a rat tumor model:
      superior antitumor activity of sustained-release preparation.
AB  - BACKGROUND: Locoregional therapy of hepatic-metastatic disease may overcome the
      limitations of systemic therapy by allowing tumor drug dose intensification
      without increasing systemic toxicity. This may result in improved efficacy. We
      have demonstrated that the novel topoisomerase I inhibitor 9-Aminocamptothecin (9
      AC) when dissolved in Ethiodol acts as a sustained release preparation, with good
      antitumor activity. Its benefit as a depot hepatic intraarterial (i.a.) therapy
      for hepatic metastases was compared to systemic therapy with an aqueous colloidal
      dispersion (CD) preparation of 9-AC in a rat model, since a lack of demonstrable
      benefit of the locoregional therapy, would argue against further clinical
      evaluation. METHODS: Fisher rats underwent direct intraportal injection of 2 x
      10(5) MADB106 adenocarcinoma cells and were treated 6 to 7 days later with: (a)
      bolus i.a. 9-AC (60 micrograms) in 60 microliters of Ethiodol; (b) bolus i.a.
      CD/9-AC (60 micrograms) in 200 microliters water; (c) bolus i.a. Ethiodol only
      (60 microliters), or (d) CD/9-AC (60 micrograms) in 200 microliters water, via a
      mini-osmotic pump pumping at 1 microliter/hr for 7 days intraperitoneally (i.p.).
      Livers were harvested 10 to 12 days later, and the number of metastases on the
      surface were counted blindly. RESULTS: Bolus hepatic i.a. 9-AC/Ethiodol was found
      to be significantly superior in reducing the number of hepatic metastases, when
      compared to the aqueous CD preparation administered in the same manner, or by
      continuous infusion via mini-osmotic pump i.p. (p < 0.01). Systemic therapy was
      also associated with substantial toxicity. CONCLUSIONS: These results suggest
      that locoregional therapy of hepatic neoplasms with 9-AC/Ethiodol would be
      associated with clinical efficacy far exceeding that associated with its systemic
      administration.

PMID- 9181238
TI  - Increased endothelial cell retraction and tumor cell invasion by soluble factors
      derived from pancreatic cancer cells.
AB  - BACKGROUND: Tumor cells induce endothelial cell retraction before invasion. In
      pancreatic cancer cells, the factors affecting endothelial cell retraction are
      not well-understood. METHODS: The activities of the endothelial cell retraction
      in conditioned media (CM) derived from three human pancreatic cancer cell lines,
      PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular
      junctional transport of FITC dextran through an endothelial cell monolayer in a
      transwell cell culture system. RESULTS: The CM derived from the three pancreatic
      cancer cells induced endothelial cell retraction. The endothelial cell retraction
      activity in the CM from PSN-1 cells was significantly higher than those from
      MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion
      and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial
      cell retraction activity in the CM from PSN-1 cells were characterized as heat
      stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in
      molecular weight, and were found both in heparin-bound and unbound fractions.
      CONCLUSIONS: PSN-1 cells produced and secreted at least two factors inducing the
      endothelial cell retraction. The factors could play an important role in the
      establishment of invasion and metastasis of PSN-1 cells.

PMID- 9181239
TI  - Medical device reprocessing: research and practice.

PMID- 9181240
TI  - Cleaning techniques for medical devices: biofilms.

PMID- 9181241
TI  - Current health care trends and their impact on clinical engineering.

PMID- 9181242
TI  - Automatic external defibrillators for public access defibrillation:
      recommendations for specifying and reporting arrhythmia analysis algorithm
      performance, incorporating new waveforms, and enhancing safety. A statement for
      health professionals from the American Heart Association Task Force on Automatic
      External Defibrillation, Subcommittee on AED and Efficacy.
AB  - These recommendations are presented to enhance the safety and efficacy of AEDs
      intended for public access. The task force recommends that manufacturers present
      developmental and validation data on their own devices, emphasizing high
      sensitivity for shockable rhythms and high specificity for nonshockable rhythms.
      Alternative defibrillation waveforms may reduce energy requirements, reducing the
      size and weight of the device. The highest levels of safety for public access
      defibrillation are needed. Safe and effective use of AEDs that are widely
      available and easily handled by non-medical personnel has the potential to
      dramatically increase survival from cardiac arrest.

PMID- 9181243
TI  - Technical and economic feasibility of reusing disposable perfusion cannulae.
AB  - The reuse of disposable devices is a potential source of significant cost savings
      to hospitals. Venous and arterial perfusion cannulae under new and reused
      conditions were selected to identify the clinical, safety, technical, logistic,
      and economic issues that must be addressed to realize these savings. Single- and
      dual-stage venous and arterial cannulae from two manufacturers were tested when
      new, after initial clinical use, and after a single clinical use plus up to nine
      simulated reuses. Reuse was simulated by end-to-end bending, coupling and
      uncoupling the connectors, and by two 1-hour soaks in plasma at 4 degrees C and
      40 degrees C, respectively. Cannulae were decontaminated and then sterilized by a
      peracetic acid based liquid chemical sterilization system following each
      use/reuse. Sterilization was validated by eliminating Bacillus subtilis spores
      from the cannulae on each of five consecutive cycles. Cannulae were tested for
      physical changes, functional integrity, biocompatibility, and in vivo performance
      in sheep. A cost minimization analysis was also performed. No clinically
      important differences were found between new and reused cannulae, even after nine
      simulated reuses. Mechanical changes were less than 20% on all variables studied
      and were undetectable by experienced cardiac surgeons in selective evaluation.
      Sterilization was successfully achieved. Reusing cannulae for times would reduce
      the cost per procedure from $53 to $19 (64%). Perfusion cannulae tested can be
      safely and efficaciously used five times. This study suggests that reuse would
      result in a small incremental savings; however, with more expensive devices and
      higher-volume sterilization procedures, the savings could be exponentially
      greater. Although this study demonstrates that it may be technically feasible and
      cost-effective to reuse disposable cannulae, the U.S. Food and Drug
      Administration does not sanction the reuse of disposable cannulae.

PMID- 9181244
TI  - A compact cryosurgical apparatus for minimally invasive procedures.
AB  - A new liquid-nitrogen-based apparatus for minimally invasive cryosurgery is
      presented. The cryoprobe was designed for application to breast tumors; however,
      it can be used for the treatment of other tumors. The cryoprobe has three major
      components, a cryoneedle, a thermal insulation shell, and a protective tube,
      which may be assembled as part of the operation. This special assembly keeps
      destruction to surrounding tissues due to cryoprobe penetration minimal, and
      allows accurate localization of the cryoprobe tip by means of stereotactic or
      needle-localization techniques. An alternative cryoprobe consists of a cryoneedle
      and a thermal insulation shell, which are rigidly connected. The liquid nitrogen
      supply system has two major components, an air-pressure source and a liquid
      nitrogen container, which are physically separated. This special configuration
      allows placement of the liquid nitrogen container adjacent to the cryotreated
      tissue and decreases the length of the cryoprobe feeding tube. In turn, heat
      losses to the surroundings are reduced, and therefore coolant consumption is
      reduced. The short feeding tube allows safe operation at low pressures. The small
      size of the apparatus makes it attractive for cryosurgical operations. It has
      been evaluated in gelatin solutions and in porcine skeletal muscle and liver. In
      vivo results do not differ significantly from those obtained in gelatin solutions
      with regard to the dimensions of frozen regions. Using a three cryoprobe
      configuration, a frozen region with an average diameter of 50 mm and a length of
      75 mm was obtained within 11 minutes. The thermal efficiency of that procedure
      was found to be 43%.

PMID- 9181245
TI  - Simultaneous multiple-modality therapy for tension headaches and neck pain.
AB  - Eighty-one patients suffering from neck pain and tension-type headaches were
      treated by the application of a unique physical therapy device combining
      transcutaneous electrical nerve stimulation (TENS), traction, massage, vibration,
      and acupressure applied to the forehead, posterior cervical spine, and scapula.
      The device employed eight silver silicone electrodes for modality application.
      Its safety and effectiveness were assessed by evaluating patients before and
      after treatment. No complication ensued. Statistical analysis of visual analog
      scales for neck pain and headache yielded p values < 0.0001. Analysis of
      fibromyalgia neck and shoulder trigger points with three controls gave
      nonsignificant results. Conclusions were that 1) the device is safe and effective
      as judged by subjective patient input and 2) fibromyalgia trigger points are
      unaffected by the treatments. More objective measures are needed to provide
      evidence of efficacy.

PMID- 9181246
TI  - Critique of arrhythmia detectors based on heuristic rules.
AB  - Every arrhythmia detector employs a beat classifier to discriminate between
      normal (N) and ventricular (V) beats. In most of these beat-classification
      algorithms, a set of rules is employed to distinguish between N and V beats using
      a common set of features extracted from the real-time ECG signal and/or
      correlation of QRS complexes with the dominant QRS template. A common set of
      these features includes: beat area, beat width, beat amplitude, beat polarity,
      and R-to-R interval. Heuristic methods are commonly used to adapt the rules to
      particular databases. These classifiers are rule-based classifiers that employ
      AND-OR binary structures and hand-tuned thresholds for making decisions in the
      feature space. The complexity of the feature space increases as the number of
      features increases. For k features, a k-dimensional space is required. Thus, the
      separation between N and V space distributions becomes more difficult, especially
      since these distributions overlap. When AND-OR binary structures with hand-tuned
      thresholds or linear-separation techniques are used to separate N and V
      distributions in a k-dimensional feature space, errors are guaranteed, because
      these distributions are not linearly separable. As a results, these algorithms
      have limited dynamic ranges. This means that the sensitivity for a certain class
      of beats (N or V) will grow only at the expense of positive predictivity for that
      class, and vice versa.

PMID- 9181247
TI  - International standards: a smaller (and easier) world.

PMID- 9181248
TI  - Clinical engineering cannot do benchmarking.

PMID- 9181250
TI  - Is hypertension a risk factor for cancer?

PMID- 9181249
TI  - Blood gas physiology.

PMID- 9181251
TI  - Effects of calcium antagonists on the risks of coronary heart disease, cancer and
      bleeding. Ad hoc subcommittee of the Liaison Committee of the World Health
      Organisation and the International Society of Hypertension.

PMID- 9181252
TI  - A case of renin-producing juxtaglomerular tumor: effect of ACE inhibitor or
      angiotensin II receptor antagonist.
AB  - We report a case of a renin-producing juxtaglomerular cell tumor and the effects
      of angiotensin-converting enzyme (ACE) inhibitor captopril or angiotensin II
      receptor antagonist TCV-116. A 19-year-old female visited our clinic because of
      hypertension (162/122 mmHg). Plasma renin activity (PRA) was 25 ng/ml/h and
      plasma aldosterone concentration (PAC) was 880 pg/ml. Abdominal sonography
      revealed a low echoic tumor in the center of the right kidney. The mass was shown
      to have isodensity on a computed tomography scan, iso- or slightly lower
      intensity on T1-weighted magnetic resonance imaging (MRI), and low intensity on
      T2-weighted MRI. Renal angiography disclosed a hypovascular tumor. Plasma renin
      activity was not decreased in response to oral administration of captopril (50
      mg) or TCV-116 (4 mg), which is associated with a marked decrease in PAC and
      blood pressure. The average of the mean blood pressure determined by an
      ambulatory monitoring system every hour for 24 h was lowered from 118 +/- 10.6
      (SD) to 85 +/- 11.4 mmHg by TCV-116. Plasma renin activity did not show any
      difference between the right and left renal vein. Removal of the tumor
      successfully decreased PRA to 0.3 ng/ml/h and PAC to 33 pg/ml, resulting in a
      decrease in 24-h average of the mean blood pressure to 78 +/- 16.9 mmHg. The
      tumor was well capsulated and stained with an antibody against mouse renin. In
      the tumor, but not normal tissues, renin mRNA was detected at 1.6 kb using rat
      renin cDNA. The content of active renin in the tumor amounted to 182 micrograms/g
      tissue, which is 109 times higher than that in normal tissue. The plasma- or
      tumor-inactive renin concentration was 3.6- or 1.8-fold the active renin
      concentration, respectively. These results suggest that the juxtaglomerular tumor
      had an MRI image of iso- to low intensity on T1 and low intensity on T2, and that
      renin secretion from the tumor may be due mainly to the constitutive pathway and
      angiotensin II receptor antagonist, as well as to ACE inhibitors, and may be very
      effective for lowering the blood pressure.

PMID- 9181253
TI  - Circulating kallikreins during sodium chloride infusion in normal and
      hypertensive humans.
AB  - The stimuli generating kinins participating in blood pressure, volume and sodium
      homeostasis and their origin are not fully known. We studied the effects of a
      combined sodium and volume load on circulating plasma and tissue kallikreins.
      Normal saline (2000 ml) was infused over 4 h in 14 subjects with primary
      hypertension and 15 age- and sex-matched normotensive control subjects. The
      infusion increased blood pressure slightly in both groups. Plasma prekallikrein
      levels fell in both groups (normotensives: 98 +/- 4 to 87 +/- 5%, p = 0.002;
      hypertensives: 106 +/- 5 to 94 +/- 6%, p = 0.003), but more rapidly in
      normotensives. Circulating tissue kallikrein did not change significantly in the
      normotensive group but was reduced in the hypertensive group. Sodium excretion
      during the infusion correlated negatively with changes in plasma prekallikrein
      and positively with plasma levels of tissue kallikrein in the normotensive group
      only. Urinary tissue kallikrein excretion during the infusion increased
      significantly only in the normotensive group. The levels or changes of
      circulating prekallikrein and tissue kallikrein were not related to the levels or
      changes in blood pressure in any of the groups. In the hypertensive group there
      was a negative correlation between blood pressure changes and urinary sodium and
      tissue kallikrein excretion. Thus, in normotensive subjects an acute sodium and
      volume load appears to activate the plasma kallikrein system and the activation
      correlates with sodium excretion. There are subtle differences in subjects with
      primary hypertension. The relevance of these differences with respect to the
      pathogenesis of primary hypertension remains to be evaluated.

PMID- 9181254
TI  - Whole blood viscosity, blood pressure and cardiovascular risk factors in healthy
      blood donors.
AB  - Whole blood viscosity contributes to the total peripheral resistance and has been
      suggested to be a risk factor for cardiovascular disease. Whole blood viscosity
      was measured using a direct technique in 105 healthy blood donors and in addition
      to establishing our reference values, the relationship to blood pressure and
      other cardiovascular risk factors was assessed. Whole blood viscosity correlated
      with systolic blood pressure (r = 0.29, p = 0.003), cholesterol (r = 0.21, p =
      0.034), cholesterol/HDL cholesterol ratio (r = 0.33, p = 0.01), triglycerides (r
      = 0.37, p < 0.0005), body mass index (r = 0.29, p = 0.003) and waist-hip ratio (r
      = 0.30, p = 0.002). Subjects with systolic blood pressure > 130 mmHg (n = 16) had
      higher whole blood viscosity (p = 0.017) than those with lower blood pressure.
      Whole blood viscosity was significantly lower in women (n = 52) than in men at
      all shear rates (0.045 > p > 0.001). These results suggest that even in a
      population of healthy normotensive blood donors of a wide age range and either
      gender, there are positive correlations between directly assessed whole blood
      viscosity and a number of the components of the metabolic cardiovascular syndrome
      including systolic blood pressure, weight and blood lipids.

PMID- 9181255
TI  - Proximal tubular function in essential hypertensives on beta-blocker therapy with
      atenolol.
AB  - Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during
      waterloading and constant infusion of [131I]hippuran and [125I]iothalamate in 24
      mild to moderate essential hypertensive patients before and after 3.5 months
      treatment with atenolol. Clearances of sodium and potassium were measured 2-3
      hours post-dosing and renal vascular resistance (RVR) and filtration fraction
      (FF) were calculated. Measurement of clearance of lithium (CLi) and uric acid
      (Curic acid) was employed to investigate specifically proximal tubular function.
      Beta-blockade with atenolol produced a borderline significant decrement in RPF
      but no change in GFR, RVR and FF. There was a significant reduction in CLi,
      fractional proximal escape of sodium and water, Curic acid and an increase in
      absolute proximal reabsorption of sodium, indicating an inhibition of proximal
      tubular function. The distal tubular parameters exhibited changes tending to
      normalize excretion of sodium, but not water. Changes in RVR were inversely
      related to changes in CLi and Curic acid, suggesting unopposed alfa-adrenergic
      stimulation to be implicated in the renal counterregulation at a proximal tubular
      site following long-term administration of atenolol in essential hypertension.

PMID- 9181256
TI  - The cardiovascular response to medullary cholinergic and corticoid stimulation is
      calcium channel dependent in rats.
AB  - Experiments were performed on anaesthetized Wistar or Sprague-Dawley rats of both
      sexes. Microinjection of an acetylcholinesterase inhibitor physostigmine (0.4
      microgram/0.1 microliter/site) or acetylcholine (ACh, 25 ng/0.1 microliter/site)
      into the rostral ventrolateral medulla (rVLM) caused an increase in blood
      pressure (BP), heart rate (HR) and the pressor response produced by stimulation
      of the dorsal periaqueductal grey (dPAG) in the midbrain. Prior microinjection of
      the calcium channel blocker verapamil (0.25 microgram/0.1 microliter/site) into
      the same sites blocked the cardiovascular effect in response to the respective
      microinjection of the drugs mentioned above. Moreover, verapamil pretreatment
      blocked the pressor and tachycardiac effect induced by respective microinjection
      of corticosterone (40 ng/0.1 microliter/site) or aldosterone (40 ng/0.1
      microliter/site) into the rVLM, as well as the enhancement of the pressor
      response to stimulation of the dPAG induced by microinjection of corticoids into
      the rVLM. These results suggest that the enhancement of cardiovascular activities
      mediated by cholinergic mechanisms may be due to the activation of postsynaptic
      calcium channels of neurons in the rVLM. The corticosteroid effect seems to be
      mediated by similar mechanisms.

PMID- 9181257
TI  - Lipid metabolism and renal protection by chronic cicletanine treatment in Dahl
      salt-sensitive rats with salt-induced hypertension.
AB  - We investigated the role of lipid metabolism in renal protection by chronic
      cicletanine treatment in Dahl salt-sensitive (Dahl S) rats with salt-induced
      hypertension. Forty-four 6-week old Dahl S rats were divided into four groups:
      (1) low-salt (0.3% NaCl) control group: (2) high-salt (4% NaCl) control group;
      (3) low-dose (10 mg/kg/day) cicletanine (CICL)-treated group given a high-salt
      diet; and (4) high-dose (30 mg/kg/day) cicletanine-treated group given a high
      salt diet. The rats were treated for 6 weeks; blood pressure was measured by the
      tail-cuff method. Cicletanine significantly reduced the systolic blood pressure
      in a dose-dependent manner (223 mmHg in the high-salt controls vs 195 mmHg in the
      high-dose, high-salt group, p < 0.01). Cicletanine treatment did not affect
      plasma concentration of total cholesterol or triglyceride or free fatty acid; in
      contrast, it significantly decreased low-density lipoprotein (LDL) cholesterol
      and increased high-density lipoprotein (HDL) cholesterol. Morphological
      examination demonstrated that glomerulosclerosis in the kidney was significantly
      improved by 15% with high-dose cicletanine (p < 0.01). Multivariate analysis
      revealed that glomerular sclerosis was determined independently by LDL
      cholesterol levels and arterial injury score, but not by total cholesterol or HDL
      cholesterol levels or blood pressures. LDL cholesterol was also an independent
      predictor of urinary excretion of protein. Thus, it is suggested that cicletanine
      treatment lowers the levels of LDL cholesterol in Dahl salt-sensitive rats, and
      that besides blood pressure reduction, this decrease in LDL cholesterol level
      contributes, in part, to regression of glomerular injury in salt-induced
      hypertension.

PMID- 9181258
TI  - Delayed increase in blood pressure induced by spontaneously hypertensive rat
      plasma after high sodium intake.
AB  - Plasma from spontaneously hypertensive rats (SHR) and from patients with
      essential hypertension has been suggested to contain a substance with a delayed
      pressor effect, parathyroid hypertensive factor (PHF), associated with salt
      sensitive forms of hypertension. In order to study whether high sodium intake
      would increase plasma levels of PHF-like activity, determined by bioassay, SHR
      received either a high-sodium (2.6% Na in the chow) or a normal-sodium (0.3% Na)
      diet for 6 weeks. Intravenous injection of plasma from SHR on a high-sodium diet
      (6 ml/kg) to urethane-anaesthetized Wistar rats induced a delayed increase in
      mean arterial blood pressure 70-80 min after bolus injection. No delayed pressor
      effects could be demonstrated by plasma from SHR or Wistar rats on a normal
      sodium diet. It is concluded that a factor with a delayed blood pressure
      increasing effect appears to be present in plasma from SHR on a high-sodium diet
      but not in plasma from normotensive Wistar rats or SHR on a normal-sodium diet.
      Further studies to characterize this factor and its possible relation to salt
      induced hypertension are warranted.

PMID- 9181259
TI  - Do we achieve maximum medical therapy for patients with chronic ischemic heart
      disease?

PMID- 9181260
TI  - Abnormalities of the S-T segment--Part I.
AB  - The usual normal S-T segment of the surface electrocardiogram (ECG) contributes
      little to the diagnostic procedure. When the S-T segment is too long or too
      short, or when it is displaced upward or downward, it is commonly abnormal. Under
      such circumstances, an S-T segment abnormality usually contributes considerable
      diagnostic information. When the Grant method of ECG interpretation is used, it
      is possible to perceive abnormalities of the S-T segment that may otherwise be
      ignored or misinterpreted. This paper describes the method of identification and
      the significance of primary and secondary S-T segment abnormalities. When a mean
      vector constructed for the S-T segment displacement seen in 12 ECG leads is
      relatively parallel with a mean vector representing the T wave, it is, with a few
      exceptions, part of the repolarization process and is therefore part of the T
      wave. This may be called a secondary S-T segment abnormality. When a mean vector
      constructed for the S-T segment displacement seen in 12 ECG leads is not
      relatively parallel with a mean vector representing the T wave, it is, with a few
      exceptions, not part of the repolarization process and is therefore not part of
      the T wave. This may be called a primary S-T segment abnormality.

PMID- 9181261
TI  - The "open artery hypothesis" in survivors of myocardial infarction.
AB  - In survivors of acute myocardial infarction, the restoration of antegrade flow in
      the infarct-related coronary artery may improve prognosis by a mechanism
      independent of its effect on left ventricular function. Survival may be enhanced
      even when restoration of flow is accomplished days or weeks after the acute
      event. In a series of retrospective studies of survivors of a first myocardial
      infarction, it was shown that long-term survival is significantly better in those
      with than in those without antegrade flow in the infarct-related artery. It is
      hypothesized that late restoration of antegrade flow in the infarct-related
      artery renders the border zone of the infarction more electrically stable,
      thereby diminishing the incidence of ventricular tachyarrhythmias and sudden
      death.

PMID- 9181262
TI  - Imaging techniques for coronary artery disease: current status and future
      directions.
AB  - We review the current status and future directions of sestamibi single-photon
      emission-computed tomography (SPECT), position emission tomography (PET),
      magnetic resonance imaging (MRI), and contrast perfusion echocardiography (CPE)
      for coronary artery disease evaluation. Diagnostic accuracy and adjunctive
      assessment of ventricular function make sestamibi SPECT the currently favored
      stress imaging radioisotope technique. Tissue attenuation correction will likely
      enhance these capabilities of SPECT in the near future. PET potentially offers
      valuable diagnostic information, as it may be a superior technique where body
      habitus limits cardiac imaging. We project that it is unlikely to become
      routinely used for cardiac imaging because of improvements in routine
      radionuclide imaging and the lack of evidence that the small resolution gain with
      PET is of importance, given the much larger cost. Cardiac MRI for assessing
      cardiac function, perfusion, and coronary angiography is an exciting new modality
      at an early stage of development. The possible comprehensive nature of MRI for
      coronary artery disease evaluation, potential cost savings related to utilization
      of a single, noninvasive test, and availability of scanning equipment in current
      community settings all project an important role for MRI in the future. Contrast
      perfusion echocardiography is also a relatively new and untested imaging modality
      which offers great future promise. The recent development of intravenous contrast
      agents and the current widespread availability of echocardiographic expertise and
      equipment throughout the country suggest that the speed of development as well as
      the dispersion of technologic advances will be rapid. We project that these
      techniques will play important roles in future coronary artery disease testing
      and will result in improved diagnostic efficacy and possibly cost utility.

PMID- 9181263
TI  - QT dispersion ratio in patients with unstable angina pectoris (a new risk
      factor?).
AB  - BACKGROUND: QT dispersion has been shown to be associated with fatal arrhythmias
      and sudden death in coronary artery disease. A recent study indicated that marked
      QT dispersion in electrocardiograms (ECGs) obtained during acute ischemia
      demonstrated a significant correlation with ventricular fibrillation. HYPOTHESIS:
      This study investigated the ECG parameters for repolarization (QT dispersion,
      corrected QT, corrected QT dispersion, and QT dispersion ratio) and their
      interrelation with acute ischemia. METHODS: QT parameters as well as a newly
      developed repolarization index, QT dispersion ratio [(QT dispersion/RR interval)
      x 100] were calculated digitally during rest and ischemia in 32 patients with
      coronary artery disease (rest angina, Braunwald class III). Results were
      correlated with clinical consequences, mainly arrhythmias, within a follow-up
      period of 5 +/- 2 days. RESULTS: While most patients had an increase in all four
      parameters, only the QT dispersion ratio showed a significant difference when
      correlated with ventricular arrhythmias (p < 0.001, F ratio = 38). CONCLUSION: QT
      dispersion ratio appears to be a new and promising parameter in predicting
      ventricular arrhythmias in patients with acute ischemia.

PMID- 9181264
TI  - Isolated and preclinical impairment of left ventricular filling in insulin
      dependent and non-insulin-dependent diabetic patients.
AB  - BACKGROUND: Diabetes mellitus can induce a pattern of myocardial pathology known
      as specific diabetic cardiomyopathy, even if this is not clearly specified.
      HYPOTHESIS: The aim of our study was to evaluate the presence of preclinical
      myocardial damage in insulin- and non-insulin-dependent diabetic patients and
      controls by assessment with Doppler echocardiography. METHODS: Twenty insulin
      dependent diabetic (IDDM) patients, 10 non-insulin-dependent diabetic (NIDDM)
      patients, and 12 healthy individuals (C) as controls, matched for age, gender,
      and without overt cardiovascular disease, were assessed in this study. RESULTS:
      Systolic function parameters presented normal values in the three groups, with
      the exception of a slight reduction in ventricular volume indices in the NIDDM
      group. Diastolic function was clearly impaired in both groups of patients versus
      that in healthy controls. In particular, ventricular filling was impaired in the
      NIDDM compared with the IDDM patients, especially the peak early filling rate E
      (p < 0.001). Moreover, in the IDDM group, the duration of diabetes (p < 0.01) and
      glycosilated hemoglobin value (HbA1C, p < 0.02) were higher than in the NIDDM
      group. Multiple regression analysis showed a significant inverse correlation
      between HbA1C and peak late filling rate A (R2 = 0.28) in both groups of patients
      and a direct correlation between velocity time integral E and age, duration of
      diabetes, and HbA1C (R2 = 0.46). The two groups presented a small, homogeneous
      number of cases with initial microangiopathy and borderline autonomic neuropathy,
      associated with microalbuminuria. Doppler echocardiography showed an early
      impairment of left ventricular filling, as well as an early preclinical
      alteration of myocardial function in diabetic patients, especially in the NIDDM
      group. CONCLUSION: These early signs of cardiomyopathy could constitute a
      predisposing condition toward the high cardiac morbidity and mortality rate in
      diabetic patients.

PMID- 9181265
TI  - The effect of iron overload in the hearts of patients with beta-thalassemia.
AB  - BACKGROUND AND HYPOTHESIS: An important complication of beta-thalassemia is iron
      deposition in cardiac tissues resulting in fibrosis and dysfunction. Our aim was
      the investigation of the possible clinical effect of iron loading in the heart of
      patients with beta-thalassemia prior to the appearance of symptoms of depressed
      systolic function. METHODS: Thirty-five patients with beta-thalassemia, of whom
      24 had the major type (Group 1) and 11 had the intermedia type (Group 2) were
      studied. Eleven age- and gender-matched controls were also studied (Group 3). All
      patients were evaluated echocardiographically and were shown to have normal left
      ventricular systolic function and dimensions. Serum ferritin, atrial natriuretic
      peptide (ANP), left atrial diameter (LAD), peak early mitral inflow velocity (E),
      peak late mitral inflow velocity (A), E/A ratio, deceleration time of the mitral
      inflow E wave (DT), and isovolumic relaxation time (IVRT) were measured. RESULTS:
      Univariate analysis showed that both groups of patients had similarly increased
      LAD and ANP plasma levels. Group 1 had a higher E/A ratio (2.27 +/- 0.88) SS than
      Group 2 (1.69 +/- 0.47, p = 0.05) and Group 3 (1.50 +/- 0.38, p = 0.01). Serum
      ferritin was significantly higher in Group 1 (3.526 +/- 0.352) than in Group 2
      (2.808 +/- 0.288, p < 10(-5) and Group 3 (2.139 +/- 0.124, p < 10(-5).
      Multivariate analysis showed that ANP is a factor that is affected by the LAD and
      E/A ratio and that serum ferritin levels affect the LAD and E/A ratio.
      CONCLUSIONS: Although LAD and ANP levels are increased in patients with beta
      thalassemia, the increased serum ferritin levels of patients seem to affect left
      atrial size and E/A ratio. ANP secretion is consecutively affected by these
      factors.

PMID- 9181266
TI  - Routine arterial oxygen saturation monitoring is not necessary during
      transesophageal echocardiography.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is now an established adjunct
      to routine echocardiography, its diagnostic impact making it an invaluable first
      line diagnostic procedure in many cardiac conditions. However, there is no
      unanimity in the way the transesophageal procedure is carried out, especially
      with regard to the need for antibiotic prophylaxis, sedation, and the monitoring
      of oxygen saturation. HYPOTHESIS: This study was prospectively undertaken (1) to
      determine the presence and magnitude of oxygen desaturation and (2) the changes
      in heart rate and blood pressure following sedation for routine TEE in an
      unselected and consecutive group of patients to identify those at high risk.
      METHODS: Arterial oxygen saturation, heart rate, and systolic, diastolic, and
      mean blood pressure were monitored in 106 consecutive patients undergoing routine
      transesophageal echocardiography. Ninety-four (89%) patients received intravenous
      sedation with midazolam. RESULTS: Three min after midazolam administration there
      was a drop in oxygen saturation from 97 +/- 2.5 to 95 +/- 2.9 (p < 0.001), in
      systolic blood pressure from 139 +/- 19.5 to 124.8 +/- 22.2 mmHg (p < 0.001), in
      diastolic blood pressure from 86.6 +/- 19.9 to 77.5 +/- 17.7 mmHg (p < 0.001),
      and in mean blood pressure from 108.3 +/- 18 to 95.6 +/- 28.8 mmHg (p < 0.001).
      After introduction of the transesophageal probe and during the examination, there
      was a further drop in oxygen saturation with a maximum drop at the 15th min of
      the examination (93.7 +/- 3.7 vs. 97 +/- 2.5, p < 0.001). The maximum blood
      pressure drop occurred at the 12th min into recovery: systolic blood pressure
      dropped from 139 +/- 19.5 to 118 +/- 20.8 mmHg (p < 0.001), diastolic blood
      pressure from 86.6 +/- 16.9 to 75.8 +/- 17.9 mmHg (p < 0.005), and mean blood
      pressure from 108.3 +/- 18 to 92.5 +/- 19.4 mmHg (p < 0.01). Patients with
      congestive heart failure had a greater drop in oxygen saturation compared with
      patients who were not in heart failure (p < 0.01). Twelve patients did not
      receive any sedation; however, they all showed a drop in oxygen saturation from
      97.8 +/- 2.3 to 94.6 +/- 3.4 (p < 0.001), with a maximum drop at the 15th min
      during the transesophageal examination. CONCLUSION: In patients with no chronic
      obstructive airway disease who are not in congestive heart failure, routine
      oxygen saturation monitoring is not deemed necessary during transesophageal
      examination. The cause of hypoxemia during the procedure is not only related to
      sedation but also to esophageal intubation.

PMID- 9181267
TI  - Left atrial size is the major predictor of cardiac death and overall clinical
      outcome in patients with dilated cardiomyopathy: a long-term follow-up study.
AB  - HYPOTHESIS: This study was undertaken to determine whether echo-derived left
      atrial dimension and other echocardiographic, clinical, and hemodynamic
      parameters detected at the time of entry into the study may influence prognosis
      in patients with dilated cardiomyopathy during a long-term follow-up. METHODS:
      This was a prospective cohort analysis of 123 patients with dilated
      cardiomyopathy. Clinical evaluation, chest x-ray, M-mode and two-dimensional
      echocardiogram, exercise test, 72-h ambulatory electrocardiogram monitoring, and
      cardiac catheterization study were performed in all patients. The study was
      divided into two phases: in the first phase, patients were divided into two
      groups according to the left atrial size (> or = 45 mm; < 45 mm), with cardiac
      death as the end point. In the second phase, all patients were further divided
      into two groups according to their clinical course. A multivariate analysis was
      performed to determine independent correlated parameters of cardiac mortality and
      overall clinical outcome. RESULTS: Cardiac mortality rate was 47.9%: 29% in the
      group without left atrial dilation and 54.3% in the group with dilated left
      atrium. Multivariate analysis revealed that left atrium > or = 45 mm, New York
      Heart Association functional classes III/IV, and the presence of one or more
      episodes of ventricular tachycardia at Holter monitoring were independent
      predictors of cardiac mortality, while left atrium > or = 45 mm, left ventricular
      end-diastolic pressure > 17 mmHg, and exercise tolerance < or = 15 min were
      independent predictors of poor clinical outcome. CONCLUSIONS: Our results
      revealed that left atrial size is the principal independent predictor of
      prognosis in patients with dilated cardiomyopathy in that patients with left
      atrial dilation had an increase in mortality and a worse clinical outcome
      compared with those without left atrial dilation.

PMID- 9181269
TI  - Detection of significant residual stenosis of the infarct-related artery after
      thrombolysis by high-dose dipyridamole echocardiography test: is it detected
      often enough?
AB  - BACKGROUND AND HYPOTHESIS: It has been reported that high-dose dipyridamole
      echocardiography test (DET) can be successfully used for the detection of
      critical residual stenosis of the infarct-related artery (IRA). However, we have
      recently noticed low sensitivity of DET for the detection of residual IRA
      stenosis in patients with single-vessel disease. This study sought to determine
      the value of DET for the detection of significant residual stenosis of the IRA
      after thrombolysis. METHODS: Dipyridamole echocardiography test was performed in
      55 consecutive patients after a first acute myocardial infarction before hospital
      discharge. All patients underwent coronary angiography 23 +/- 6 days after
      infarction. RESULTS: Nine of 19 patients with positive DET revealed new adjacent
      asynergy and all of the patients had patient and significantly stenotic IRA.
      Sensitivity and specificity of DET in identifying significant residual stenosis
      of the IRA were 24 and 100%, respectively. Among 49 patients with significantly
      stenotic of occluded IRA, 40 patients without adjacent asynergy during DET had
      higher baseline wall motion score index (WMSI) compared with 9 patients who
      revealed adjacent asynergy during DET (1.45 +/- 0.30 vs. 1.24 +/- 0.18; p <
      0.05). When all patients with positive DET (adjacent or remote asynergy) were
      compared with those with negative DET, no difference in baseline WMSI was found
      (1.37 +/- 0.24 vs. 1.44 +/- 0.24; p > 0.05). CONCLUSIONS: Our data indicate that
      sensitivity of DET in detecting significant residual stenosis of the IRA after
      thrombolysis is low. It seems that the extent of myocardial infarction affects
      the ability of DET to detect adjacent, but not remote asynergy.

PMID- 9181270
TI  - Role of transesophageal echocardiography in the clinical management of a patients
      with a giant coronary artery aneurysm.
AB  - Transthoracic echocardiography (TTE) has substantial limitations for the study of
      abnormalities of the coronary tree. Transesophageal echocardiography (TEE) allows
      a more complete examination of the coronary arteries, particularly the proximal
      segments. This report describes the use of TEE after cardiac catheterization in
      the clinical management of a patient with unstable angina. While angiography
      first showed the giant aneurysm of the left circumflex coronary artery. TEE, by
      revealing an active thrombus of the lumen, prompted an immediate surgical
      resolution.

PMID- 9181268
TI  - Antihypertensive effects of mibefradil: a double-blind comparison with diltiazem
      CD.
AB  - BACKGROUND AND HYPOTHESIS: Mibefradil is the first compound of a new class of
      calcium antagonists with a unique chemical structure and mechanism of action.
      This trial compared mibefradil with diltiazem CD, a widely prescribed calcium
      antagonist for the treatment of hypertension. METHODS: In all, 201 patients with
      uncomplicated, mild-to-moderate essential hypertension with a baseline sitting
      diastolic blood pressure (SDBP) of > or = 95 and < or = 114 mmHg were evenly
      randomized to receive either mibefradil (100 mg) or diltiazem CD (360 mg) daily
      for 12 weeks. To determine whether antihypertensive effects persisted after 12
      weeks, patients then entered a 4-week withdrawal period during which they
      remained on active treatment or were switched to placebo. RESULTS: Efficacy
      variables were the changes from baseline in SDBP to the end of the treatment
      period (Week 12) and during the randomized withdrawal period (Week 16). At Week
      12, the reduction from baseline in SDBP at trough was significantly greater (p <
      0.001) in the mibefradil group (-14.0 +/- 7.8 mmHg) than in the diltiazem CD
      group (-9.5 +/- 7.5 mmHg). Significantly more patients (72%) on mibefradil
      achieved SDBP normalization by Week 12 than did patients on diltiazem (51%) (p <
      0.01). Patients maintained on mibefradil or diltiazem CD during the withdrawal
      period had a significantly larger reduction in trough SDBP at Week 16 than those
      switched to placebo. The incidence of side effects was similar in both treatment
      groups. CONCLUSIONS: Once-daily mibefradil was equally well tolerated as
      diltiazem CD, but was more effective in lowering blood pressure at the doses
      studied than the extended-release formulation of diltiazem.

PMID- 9181271
TI  - Eustachian valve endocarditis: detection with multiplane transesophageal
      echocardiography.
AB  - Right-sided involvement is fairly common in infective endocarditis, but
      involvement of the eustachian valve is distinctly rare. We present the case of a
      36-year-old intravenous drug user with staphylococcal bacteremia and septic
      pulmonary emboli. Transthoracic echocardiography was normal, but transesophageal
      echocardiography revealed a large eustachian valve vegetation. This case
      illustrates the utility of multiplane transesophageal echocardiography in the
      evaluation of eustachian valve pathology.

PMID- 9181272
TI  - Myocardial bridging in a young patient with sudden death.
AB  - Systolic compression of a coronary artery is considered to be a benign
      phenomenon, although numerous case reports have suggested an association between
      bridging and sudden death or ischemia in certain patients without other
      abnormalities on cardiovascular evaluation. We present the case of a young
      patient with two episodes of spontaneous ventricular fibrillation and
      electrocardiographic evidence of ischemia, whose only primary abnormality on
      extensive workup was a long segment of left anterior descending systolic
      compression. This case adds to the growing body of anecdotal evidence that
      myocardial bridging may be associated with significant cardiac events.

PMID- 9181273
TI  - J. Willis Hurst--a man of achievement.

PMID- 9181274
TI  - Pregnancy in women with impaired renal function.
AB  - The outcome and consequences of pregnancy in women with impaired renal function
      are still debated. To assess the benefit of recent advances in coordinated
      obstetrical and nephrologic management, we analyzed fetal and maternal outcome of
      43 pregnancies in 30 women with various types of primary renal disease and
      moderate to severe renal failure at conception defined by serum creatinine
      concentration (Scr) ranging from 0.11 to 0.49 mmol/l. All pregnancies took place
      during the 20-year period from 1975 through 1994 and were prospectively followed
      jointly by our Nephrology Unit and Obstetric and Neonatology Units of University
      Hospitals. Of the 43 pregnancies (45 fetuses), 13 ended in fetal death (including
      5 first-trimester abortions and 8 fetal deaths beyond the 20th gestational week).
      There were 32 live births, a success rate of 82% not considering first-trimester
      abortions. Successful pregnancies were significantly more frequent in the last
      decade than in the preceding one (91 vs 65%, p = 0.05). Overall live birth rate
      was higher in pregnancies started with Scr < 0.20 mmol/l than in those with Scr >
      0.20 mmol/l (80% vs 53%, p = 0.02). The upper preconception Scr value associated
      with a successful fetal outcome was 0.27 mmol/l. Hypertension was the major
      factor of fetal prognosis, as the relative risk of fetal loss was 10.6 times
      higher when hypertension was present at conception or early in pregnancy than
      when blood pressure was spontaneously normal or well-controlled by therapy. An
      accelerated course toward end-stage renal failure was observed in 7 patients
      (23%), all of whom had severe hypertension and heavy proteinuria at conception.
      We conclude that fetal outcome in patients with impaired renal function has been
      improved in recent years, due to advances in obstetrics and neonatology, improved
      blood pressure control and close co-operation between nephrologists and
      obstetricians, but that a risk of fetal loss and of accelerated deterioration of
      maternal renal disease still persists when Ccr at conception is lower than 25-30
      ml/ min/1.73 m2.

PMID- 9181275
TI  - T-lymphocyte populations, cytokines and other growth factors in serum and urine
      of children with idiopathic nephrotic syndrome.
AB  - The T-cell defect present in the idiopathic nephrotic syndrome (INS) was
      investigated in 29 steroid-sensitive and 14 steroid-resistant children aged 2-19
      years. Nine different lymphocyte subpopulations and 15 cytokines, receptors and
      other growth factors were measured in blood, and some also in urine. In steroid
      sensitive patients we found a decreased ratio of helper/inducer cells (CD4+)
      versus suppressor/cytotoxic cells (CD8+) in relapse and remission, and an
      increased proportion of natural killer cells (CD16+) during relapse vs long-term
      remission, as a sign of an elevated cytotoxic potential. Among the serum
      cytokines mainly produced by monocytes/macrophages interleukin (IL)-8 levels were
      decreased in steroid-sensitive patients vs controls, with normal levels observed
      for IL-1 alpha, IL-1 beta, IL-1RA and tumor necrosis factor (TNF-alpha). IL-2 was
      the only cytokine produced by TH1 cells which was significantly increased during
      relapse vs long-term remission. We also observed a trend for elevated levels of
      sIL-2R and IFN-gamma. Serum levels of cytokines derived from TH2 cells were
      variable. IL-4 was decreased during relapse but increased in patients with long
      term remission. SIL-6 receptors were increased during relapse. Finally we
      observed decreased serum levels of IL-3 and of the adhesion molecule ICAM-1 in
      active INS. Patients with steroid-resistant INS exhibited similar changes of T
      cell populations and cytokines as steroid-sensitive patients; their CD4+/CD8+
      ratio was reduced to the same degree and sIL-2R levels were even higher than in
      steroid-sensitive patients. In conclusion this study indicates that active INS is
      associated with an increased number of cytotoxic cells in the blood and an
      elevated TH1 cytokine production. Long-term remission appears to be related to
      increased TH2 cytokine production downregulating TH1 cytokines and cytotoxic
      cells. Our data give evidence that different immune mechanisms are involved in
      the pathogenesis of INS.

PMID- 9181276
TI  - Kidney vascular damage and cocaine.
AB  - Cardiovascular damage is common in young cocaine addicts, and similar
      atherosclerotic lesions seem likely in the kidneys. To confirm this hypothesis,
      we performed histological examination of 40 kidney autopsy specimens classified
      as "cocaine-related deaths"; as controls, kidney specimens of 40 road accident
      victims were examined. Semiquantitative analysis showed that the ratio of the
      number of glomeruli affected by hyalinosis to the total number of glomeruli was
      0.09 +/- 0.13 in addicts and 0.005 +/- 0.01 in controls; the difference was
      highly significant. The degree of periglomerular fibrosis was significantly
      higher in cocaine addicts than in accident victims. The ratio of glomeruli to
      tubular casts was 0.15 +/- 0.17 in cocaine addicts and 0.17 +/- 0.18 in controls
      (not significant). The degree of interstitial cellular infiltration was
      significantly higher in addicts than controls. A monunuclear cell infiltrate was
      observed prevalently in the medullary region. Arteriolar sclerosis was
      significantly higher in addicts than controls. Medial thickening, luminal
      narrowing and vessel obstruction were absent in the control group. Quantitative
      morphometric analysis of arterial structure showed significantly greater lumen
      circumference, intima circumference, media circumference, intima area, media
      area, intima thickness and media thickness in cocaine addicts than in controls.

PMID- 9181277
TI  - Abnormal distal tubular sodium reabsorption during dopamine infusion in patients
      with essential hypertension evaluated by the lithium clearance methods.
AB  - The effects of low-dose dopamine infusion on renal hemodynamics, tubular function
      estimated by the lithium clearance technique and plasma levels of angiotensin II
      (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine
      vasopressin (AVP) were studied in 11 patients with essential hypertension (HT)
      and in 10 healthy control subjects (CS). Antihypertensive treatment was
      terminated at least 2 weeks prior to examination. Dopamine (2 micrograms/kg/min)
      was infused for two hours. Before dopamine infusion all measured parameters, but
      blood pressure, did not deviate significantly between the two groups, including
      24 h urinary sodium excretion prior to investigation (HT: 166.9 mmol/24 h vs. CS:
      183.4 mmol/24 h, medians). Dopamine infusion resulted in an exaggerated
      natriuresis in the HT group when compared with the CS group; sodium excretion:
      (HT: from 260 to 759 mumol/min vs. CS: from 255 to 432 mumol/min, p < 0.01) and
      fractional sodium excretion: (HT: from 1.6 to 4.2% vs. CS: from 1.6 to 2.4%, p <
      0.01 median values). Distal fractional sodium reabsorption was significantly
      lower in the HT patients (HT: from 94.0 to 88.5% vs. CS: from 94.0 to 91.6%, p <
      0.01). ANP decreased significantly only in the HT group (HT: from 4.8 to 3.5
      pmol/l vs. CS: from 3.2 to 3.4 pmol/l, p < 0.01). Renal hemodynamics, blood
      pressure, urinary output, Ang II, Aldo, and AVP were changed to the same degree
      or unchanged in both groups. It is concluded that the exaggerated natriuretic
      response seen in patients with essential hypertension during low-dose dopamine
      infusion probably is due to a enhanced dopamine sensitivity mainly in the distal
      parts of the nephron.

PMID- 9181278
TI  - Proteinuria in mild to moderate hypertension: results of the VA cooperative study
      of six antihypertensive agents and placebo. Department of Veterans Affairs
      Cooperative Study Group on Antihypertensive Agents.
AB  - The prevalence and natural history of severe proteinuria in mild to moderate
      hypertension are not completely defined. We screened 1635 men with a history of
      hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95
      109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol,
      captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind
      prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical
      criteria for primary hypertension were found to have developed proteinuria > 1000
      mg/24 hours and were removed from the study. Follow-up data were obtained on 19
      of these 27 patients. One patient was found to have focal segmental sclerosis and
      progressed to end-stage renal disease. Three other patients developed severe
      (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic
      nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of
      the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9
      years. Data were available for 1076 of 1155 (93%) treated study patients at end
      titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were
      significant associations for proteinuria with obesity and higher systolic blood
      pressure. There was a trend toward significant difference in mean 24-hour protein
      excretion rates at baseline between black (127 mg) and white (139 mg) patients (p
      = 0.07). There were no statistically significant changes in urinary protein
      excretion/24 hours between or within the different treatment groups (including
      placebo). Eighteen patients were removed from the study during the active
      treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4,
      placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We
      conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the
      hypertensive population is significant but does not necessarily imply a poor
      prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in
      response to the different classes of antihypertensive drugs; and (3) there was no
      drug-specific increase in proteinuria detected in this study.

PMID- 9181280
TI  - Effects of different chromium compounds on blood pressure and lipid peroxidation
      in spontaneously hypertensive rats.
AB  - In a previous study, we found that oral chromium nicotinate overcame sucrose
      induced hypertension in spontaneously hypertensive rats (SHR). Accordingly, we
      examined more chromium compounds to determine if others were more or less
      effective in regulating blood pressure (BP) of SHR. Since chromium is postulated
      to be an antioxidant, we also assessed the ability of different chromium
      compounds to alter free radical formation measured by determining thiobarbituric
      acid reactive substances (TBARS). The control group of SHR ingested a diet low in
      chromium, and 5 other groups ate the same diet with various chromium compounds
      added at 5 ppm-chloride, acetate, nicotinic acid-glycine-cysteine-glutamic acid
      (NA-AA), picolinate, and nicotinate. Following this, the rats were challenged
      with drinking water containing 5% and 10% w/v sucrose. Except for NA-AA, all
      chromium compounds inhibited the sucrose-induced elevation of systolic BP; and
      acetate, picolinate, and nicotinate chromium compounds lowered HbAIC below
      control. Only chromium acetate and nicotinate significantly lowered both hepatic
      and renal TBARS. Chromium picolinate lowered hepatic TBARS, and chromium chloride
      and NA-AA lowered neither. We conclude that chromium, rather than a specific
      ligand, plays a major role in ameliorating sucrose-induced BP elevations and can
      act as an antioxidant.

PMID- 9181279
TI  - Effects of moxonidine and clonidine on renal function and blood pressure in
      anesthetized rats.
AB  - Using classical clearance techniques, the renal effects of moxonidine and
      clonidine were studied in the rat. Moxonidine (0.25 and 0.5 mg/kg body weight
      i.v.) increased transiently fractional fluid and Na+ excretion. Similarly,
      clonidine in the same i.v. doses caused a sustained increase in fractional fluid
      excretion, but only a short lasting increase in fractional Na+ excretion that was
      similar to the effect of moxonidine. Water diuresis experiments showed that the
      agonists mostly exert their actions within the proximal tubule. Antagonists such
      as idazoxan and yohimbine did not change fractional fluid excretion and Na+
      excretion by their own. Both, the nonselective imidazoline/alpha 2-adrenoceptor
      antagonist idazoxan and the pure alpha 2-adrenoceptor antagonist yohimbine
      attenuated the moxonidine induced effects on fractional fluid excretion and Na+
      excretion. The clonidine induced increase in fractional fluid and Na(+)-excretion
      was inhibited by yohimbine and desmopressin only. The effects on systemic blood
      pressure after moxonidine or clonidine application were similar. The initial
      blood pressure increases after moxonidine application, however, was less than
      with clonidine, whereas the hypotensive potency was more pronounced. Similar to
      the effects on kidney function, idazoxan and yohimbine had no influence on
      systemic blood pressure by themselves. Immediately after moxonidine application,
      a short lasting increase in renal plasma flow and glomerular filtration rate
      could be observed. Our results demonstrate, that moxonidine exerts renal effects,
      which are different from those of clonidine. At present time, renal effects
      mediated by imidazoline receptors and alpha 2-adrenoceptors cannot be clearly
      distinguished.

PMID- 9181281
TI  - Antibodies to recombinant human erythropoietin causing pure red cell aplasia.
AB  - Recombinant human erythropoietin (rHuEPO) is used extensively in anemic patients
      on dialysis and other patients and is regarded as very safe and effective in the
      management of anemia in these patients. To date, there is no report on the
      development of antibodies to rHuEPO in the patients treated with this drug. We
      report here a patient who developed antibodies to rHuEPO and as a result
      developed pure red cell aplasia. A 63-year-old black male with end-stage renal
      disease secondary to hypertension was placed on chronic dialytic therapy and
      tolerated rHuEPO treatment well for two years. A rapidly progressive anemia was
      then noted which was unresponsive to maximal doses of rHuEPO and the patient soon
      became transfusion-dependent. Bone marrow examination revealed paucity of red
      cell precursors. A detailed search for the cause of this pure red cell aplasia
      was unrevealing. Serological tests for Parvovirus B19 infection were negative.
      Antibodies for rHuEPO were tested by radioimmuno-precipitation assay and were
      found positive. In the course of several months, the antibody titer declined
      spontaneously to negligible levels with simultaneous improvement in the anemia
      and reappearance of red cell precursors in the bone marrow. This is the first
      patient to be reported who formed antibodies to rHuEPO and as a consequence
      developed pure red cell aplasia. Thus we conclude that although very rare,
      antibody production to rHuEPO should be considered in evaluating patients with
      EPO-resistant anemia with no obvious etiology.

PMID- 9181282
TI  - Case of propylthiouracil-induced vasculitis associated with anti-neutrophil
      cytoplasmic antibody (ANCA); review of literature.
AB  - A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for
      hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and
      inflammation of the nose. Examination of a renal biopsy specimen showed focal
      segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining
      showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic
      antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the
      ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti
      leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme
      were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody
      to be markedly elevated, we challenged this data by performing dot blot analysis.
      The patient's serum reacted with the native form, but not with denatured
      leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms
      abated within 2 weeks and all values of ANCA were reduced after the drug was
      withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently
      it was reported in association with ANCA. We present the findings of this patient
      and compare them with those described in 19 published cases of propylthiouracil
      induced vasculitis associated with ANCA.

PMID- 9181284
TI  - A case with renovascular hypertension.

PMID- 9181283
TI  - Renal parenchymal malakoplakia in a four-week-old infant.
AB  - We describe a four-week-old male infant with bilateral renal parenchymal
      malakoplakia who presented with low grade fever, convulsions and lethargy. The
      patient had profound anemia, hepatosplenomegaly and bilateral nephromegaly with
      reduced renal function. Both blood and urine cultures grew Escherichia coli, and
      antibiotic therapy was started. A kidney biopsy obtained on the 20th hospital day
      confirmed the diagnosis of renal parenchymal malakoplakia. Following treatment
      with an intravenous methylprednisolone pulse therapy, the infant made significant
      clinical improvement. He has grown and developed normally in the three years
      following this episode. We suggest that the steroid therapy was useful in
      ameliorating renal parenchymal malakoplakia in a patient without an underlying
      systemic disease. This report describes the youngest patient to have
      malakoplakia.

PMID- 9181285
TI  - The use of dopamine in acute renal failure.

PMID- 9181286
TI  - Oral ciprofloxacin to treat bacterial peritonitis associated with peritoneal
      dialysis.

PMID- 9181287
TI  - Incidence of tooth loss and dental caries in 60-, 70- and 80-year-old Swedish
      individuals.
AB  - The retention of natural teeth among the elderly is increasing and, in recent
      studies, dental caries has been identified as the main reason for teeth being
      extracted. The 5-year incidence of tooth loss and dental caries and the most
      crucial dental factors for tooth extraction were studied in a random sample of 60
      , 70- and 80-year-old inhabitants of Gothenburg. Of the 208 persons examined at
      baseline, 148 (71%) participated in the follow-up examination: 69, 51 and 28
      respectively in the different age groups. In all, 110 teeth had been extracted
      during the period in 40% of the participants. Only 9 persons had lost three or
      more teeth. The mean numbers of remaining teeth were 22. 18 and 15 respectively
      in the 60-, 70- and 80-year age groups and the mean numbers of teeth lost during
      the 5-year period increased with age from 0.4 in the 60-year-olds to 0.8 and 1.4
      in the 70- and 80-year-olds (P < 0.05). The major reason for tooth extraction was
      dental caries and it was found in 60% of all cases and at a higher rate of 77% in
      the oldest age group. Fifty-one per cent had developed new coronal carious
      lesions and 61% had new root carious lesions, while 27% had not developed caries
      during the period. The mean 5-year increment in decayed and filled coronal
      surfaces increased with age from 2.3 in the 60-year-olds to 3.7 and 5.3 in the 70
      and 80-year-olds (N.S.I. The increment in decayed and filled root surfaces was
      higher in women than men, 3.4 compared with 1.8 (N.S.), which also increased with
      age from 1.4 in the 60-year-olds to 2.4 and 5.5 in the 70- and 80-year-olds (P <
      0.0001). It was concluded from this study that few teeth had been lost during the
      5-year period but that dental caries still appeared to be a serious problem among
      some very elderly people.

PMID- 9181288
TI  - Clinical factors related to reported satisfaction with oral function amongst
      dentate older adults in England.
AB  - This paper aims to identify the features of a natural dentition, specifically the
      number and distribution of teeth, which are important for oral satisfaction and
      freedom from eating problems in the elderly. Data were gathered on the dental
      condition, satisfaction and function of 1211 dentate adults aged 60 years or
      over, randomly sampled from three areas in England. Multiple logistic regression
      was used to identify the clinical factors which contribute to satisfaction with
      aesthetics and the ability to bite and chew. Satisfaction with biting and chewing
      was influenced by specific reported eating problems, dry month and increasing
      age. The presence of these eating problems was related to a complex series of
      factors describing the number and distribution of teeth and dentures, and some
      variables describing symptoms and disease. Having 21 or more natural teeth and no
      removable partial dentures (odds ratio 3.2), 2 or more posterior contacting pairs
      of teeth (odds ratio 1.7), and few anterior spaces were important factors related
      to the absence of eating problems. Unfilled anterior spaces (odds ratio 3.9), and
      widespread caries and periodontal disease were associated with aesthetic
      dissatisfaction. Many of the principles of shortened dental arch are consistent
      with good function and satisfaction in the elderly.

PMID- 9181289
TI  - Extent and provision of orthodontic services for children and adolescents in
      Finland.
AB  - Orthodontic services for Finnish children and adolescents up to the age of 18 in
      1992 were monitored by a questionnaire sent to all municipal health centres
      responsible for children's dental care in Finland, and 96% responded. All health
      centres provided some orthodontic treatment, but the percentage of 0 18-year-old
      children receiving treatment ranged from 1% to 19%. One-quarter of all dental
      visits of the 0 18-year-olds were in connection with orthodontics. The timing of
      treatment was early, the average age for starting was 9.5 years. In statistical
      analyses, the number of children receiving treatment was associated with the
      timing of treatment. At the age of 7, the most frequently used appliances were
      quad helix, removable appliance and orthopaedic headgear and, at the age of 13,
      fixed appliance and activator. Most treatments were provided by nonspecialists.
      The specialist expertise needed was usually purchased from an outside
      orthodontist by means of consultation contracts. Every fifth health centre,
      usually the largest, had employed one or more specialist orthodontists. The
      regional distribution of orthodontists was uneven, emphasizing regional variation
      in the delivery of orthodontic services.

PMID- 9181290
TI  - Occlusal restorative decisions based on visual inspection--calibration and
      comparison of different methods.
AB  - The purpose of this in vitro study was to calibrate occlusal restorative decision
      making based on visual inspection (VI), and to compare it with visual inspection
      with magnifying (x1.25) lenses (VIM), and fibre-optic transillumination (VIF).
      Sixty extracted human third molars mounted in plaster were examined using VI by
      ten dentists three times during the calibration process. After wash-out periods,
      the teeth were re-examined by the same dentists using VI, VIM and VIF. The inter
      examiner reproducibility for VI, expressed as Kappa (kappa) statistics (kappa +/-
      SD), was 0.46 +/- 0.10 before and 0.59 +/- 0.11 after the calibration process and
      remained at the same level after the wash-out period. Intra-examiner
      reproducibility was substantially higher for VI (kappa -0.68 +/- 0.15) before and
      after the wash-out period. There were no significant changes in restorative
      treatment decisions based on VIM and VIF when compared to VI. The reproducibility
      between the methods was good for VI vs. VIM (kappa = 0.64) and moderate for VI
      vs. VIF (kappa = 0.56). In contrast, the inter-examiner reproducibilities
      expressed as Kappa were considerably lower for VIM (kappa = 0.46 +/- 0.17) and
      VIF (K = 0.42 +/- 0.19). It was concluded that the inter-examiner reproducibility
      can be improved with a calibration process based on a simple feedback method and
      that inter-examiner variation, especially without calibration, may be as
      important a factor for restorative treatment decisions as the diagnostic method
      itself.

PMID- 9181291
TI  - Validation of the Dental Fear Scale and the Dental Belief Survey in a Norwegian
      sample.
AB  - The aim of this study was to validate the Kleinknecht's Dental Fear Scale and the
      Getz's Dental Belief Survey in a Norwegian sample by 1) testing their ability to
      discriminate between fearful (n = 151) and regular (n = 160) patients, and 2)
      correlating them. Both instruments were highly reliable (Cronbach's alpha >
      0.90). Between 81% and 95% of the fearful and regular patients were correctly
      assigned to their appropriate groups with both instruments. It may thus be
      concluded that both instruments are valid. Also, the correlation between the
      instruments was 0.68, indicating that they to a large extent seem to measure the
      same concept. The most important predictor items for both instruments were
      related to avoidance of dental treatment.

PMID- 9181292
TI  - On the pH-lowering potential of lactobacilli and mutans streptococci from dental
      plaque related to the prevalence of caries.
AB  - The common method used today to identify persons at risk of dental caries is to
      estimate the numbers of cariogenic bacteria such as lactobacilli and mutans
      streptococci in saliva or plaque samples taken from the patient. However, the
      value of these bacterial counts for explaining and predicting individuals at risk
      of caries has not been powerful enough. Evaluating one virulence factor such as
      the acidogenicity of these bacteria might increase their explanatory values for
      caries. Sixty children aged 14-15 yrs participated in this study. Smooth surface
      caries and restorations were registered and total plaque samples collected.
      Counts of lactobacilli and mutans streptococci were estimated, and the pH
      lowering potential of both bacteria was measured in an adapted glucose broth. The
      results showed a weak association between dental caries and lactobacilli, but in
      the subgroup with this bacterium the explanatory value increased to 14% and in
      the subgroup with a strong pH-lowering potential it was as high as 27%. For
      mutans streptococci the associations were weak in all groups.

PMID- 9181293
TI  - Dental fluorosis and the use of a high fluoride-containing trona tenderizer
      (magadi).
AB  - It has recently been suggested that magadi, a high-fluoride trona, which is added
      in cooking to tenderize certain vegetables and beans in two villages in Tanzania,
      significantly contributed to the prevalence and severity of dental fluorosis.
      This report aims to substantiate the significance of magadi as a determinant of
      dental fluorosis. Eighteen villages in four geographical areas (districts) with
      water supplies containing 0.2 to 0.8 mg/L of fluoride were selected. All
      schoolchildren aged 12 to 17 years (n = 1566) who had been born and raised in
      these villages were examined for dental fluorosis according to the Thylstrup
      Fejerskov Index. Dietary history was recorded. The fluoride content of magadi
      samples was determined and the urinary fluoride excretion of pre-schoolchildren
      was assessed. The prevalence of dental fluorosis in nine coastal villages where
      tea and seafish were regularly consumed ranged from 7% to 46%. Severe (pitting)
      dental fluorosis was rarely seen. The low fluorosis levels observed in non-magadi
      consuming communities in coastal villages indicate that a fluoride content of up
      to 0.8 mg/L in drinking water is acceptable under the prevailing conditions of
      temperature and diet. In contrast, the prevalence of dental fluorosis in nine
      villages located inland at 1500 m altitude, where fluoride-containing magadi was
      consumed, ranged from 53% to 100%, and severe (pitting) fluorosis was highly
      prevalent, ranging from 18% to 97%. The village with the highest fluoride content
      in the magadi samples collected showed the highest level of fluorosis. The
      urinary fluoride excretion of pre-schoolchildren from different villages
      corresponded with the level of fluorosis and the fluoride content in the magadi
      samples of the respective villages. Data on dental fluorosis from the magadi
      consuming communities provide strong evidence that consumption of magadi was the
      major determinant of the observed high prevalence and severity of fluorosis in
      inland villages at 1500 m altitude.

PMID- 9181295
TI  - Indicators of dental extractions and full mouth clearances: a longitudinal
      analysis.

PMID- 9181294
TI  - Epidemiological survey of oral submucous fibrosis in Xiangtan City, Hunan
      Province, China.
AB  - Oral submucous fibrosis is a high risk precancerous condition and is suggested to
      be caused by areca nut chewing. Areca nut chewing is popular in Hunan Province of
      China, and is more concentrated in Xiangtan City. Two and nine cases of oral
      submucous fibrosis (OSF) were first noticed in 1984 and 1985 respectively, and an
      epidemiologic survey was subsequently performed in 1986. The epidermiologic
      method of cluster sampling was used. The Yuhu District, one of the five urban
      districts of the Xiangtan City with a population of 100,000 was selected as a
      whole body in the survey, 57 independent units of various professions were
      randomly selected as group samples and more than 70% of subjects in each unit
      were examined. Definite fibrous band on palpation was used as a main diagnostic
      criterion for OSF. A total of 11046 individuals were examined; among them were
      3907 areca nut chewers (35.37%) and 7139 non-chewers (64.63%). 335 cases of OSF
      were found, comprising a prevalence rate of 3.03%. The disease involved mainly
      the middle third of the oral cavity. All of the OSF cases were areca nut chewers.
      No case had been found in non-chewers. Four cases of oral carcinoma were found on
      the basis of OSF, the malignant transformation rate was 1.19%. The high
      prevalence of OSF may be due to areca nut chewing plus extensive and heavy use of
      hot pepper in Xiangtan people. The result supports the role of the areca nut as
      an etiologic factor in the development of OSF. The low malignant transformation
      rate of 1.19% compared with the 7.6% in an Indian report may be because Xiangtan
      people chew areca nut without tobacco.

PMID- 9181296
TI  - Caries prevalence in boys aged 2, 4 and 6 years according to socio-economic
      status in Riyadh, Saudi Arabia.

PMID- 9181297
TI  - Psychiatric distress, pain and fear in patients in general dental practice.

PMID- 9181298
TI  - Introduction to the biosafety guidelines for sorting of unfixed cells.

PMID- 9181299
TI  - Biosafety guidelines for sorting of unfixed cells.
AB  - The International Society of Analytical Cytology (ISAC) Biohazard Working Group
      presents guidelines for sorting of unfixed cells, including known biohazardous
      samples, using jet-in-air, deflected-droplet cell sorters. There is a risk that
      personnel operating these instruments could become exposed to droplets and
      aerosols containing biological agents present in the samples. The following
      guidelines can aid in the prevention of exposures of laboratory personnel to
      pathogens contained in the sort samples. The document provides biosafety
      recommendations for sample handling, operator training and protection, laboratory
      facility design, and instrument setup and maintenance. In addition, it describes
      in detail methods for assessment of instrument aerosol containment.
      Recommendations provided here may also help laboratories to obtain institutional
      and/or regulatory agency approval for sorting of unfixed and known biohazardous
      samples.

PMID- 9181300
TI  - Proposed new data file standard for flow cytometry, version FCS 3.0.
AB  - In 1984, the first flow cytometry data file format was proposed as Flow Cytometry
      Standard 1.0 (FCS1.0). FCS 1.0 provided a uniform file format allowing data
      acquired on one computer to be correctly read and interpreted on other computers
      running a variety of operating systems. That standard was modified in 1990 and
      adopted by the Society of Analytical Cytology as FCS 2.0. Here, we report on an
      update of the FCS 2.0 standard which we propose to designate FCS 3.0. We have
      retained the basic four segment structure of earlier versions (HEADER, TEXT, DATA
      and ANALYSIS) in order to maintain analysis software compatibility, where
      possible. The changes described in this proposal include a method to collect
      files larger than 100 megabytes (not possible in earlier versions of the
      standard), the inclusion of international characters in the TEXT portions of the
      file, a method of verifying data integrity using a 16-bit cyclic redundancy
      check, and increased keyword support for cluster analysis and time acquisition.
      This report summarizes the work of the ISAC Data File Standards Committee. The
      complete and detailed FCS 3.0 standard is available through the ISAC office
      [Sherwood Group, 60 Revere Drive, Ste 500, Northbrook, IL 60062, phone: (847) 480
      9080 ext. 231, fax: (847) 480-9282, E-mail: isac@sherwood-group.com] or through
      the internet at the ISAC WWW site, http://nucleus.immunol.washington.edu/ISAC.ht
      ml.

PMID- 9181301
TI  - Comparison of fixation procedures for fluorescent quantitation of DNA content
      using image cytometry.
AB  - DNA quantitation using fluorescent dyes is of interest in image cytometry in that
      it is nondestructive in its mode of staining and is compatible with techniques
      such as FISH and immunofluorescence, allowing multicolor analysis of a wide range
      of cellular markers of interest. Optimal preparation techniques were sought using
      human peripheral blood lymphocytes and fine needle samples of breast carcinomas.
      Unfixed (air-dried only), ethanol, ethanol/acetic acid, and
      paraformaldehyde/ethanol fixations were tested. Unfixed or fixed cells were
      placed on slides as a drop or by cytocentrifugation, stained with 4',6-diamidino
      2-phenylindole dihydrochloride and DNA content was measured using image analysis.
      Histogram quality was evaluated using G0G1 peak coefficient of variation, and
      compared to those generated by flow cytometry. Drop preparations of
      ethanol/acetic acid fixed and cytospin preparations of paraformaldehyde/ethanol
      fixed cells appeared to give the best histograms for image analysis, which were
      inferior in quality to those generated by flow cytometry. Comparison of breast
      carcinoma histograms generated by flow and image showed the same DNA aneuploid
      populations but with slightly higher DNA indices measured by image analysis.

PMID- 9181302
TI  - Automatic correction of the interfering effect of unsuppressed interspersed
      repetitive sequences in comparative genomic hybridization analysis.
AB  - Comparative genomic hybridization (CGH) is a relatively new technique whose
      application is increasing. The method has mostly been employed for detection of
      chromosome aberrations in cancers, and a large amount of data in this field is
      accumulating. At the same time, efforts are made to improve the technique in
      order to increase the sensitivity and the generation of reliable results. Based
      on experimental data, we have developed a computer algorithm for eliminating some
      of the interfering effects of unsuppressed repetitive sequences in CGH analysis,
      and thereby improved our CGH analysis system.

PMID- 9181303
TI  - Counting mitoses by image processing in Feulgen stained breast cancer sections:
      the influence of resolution.
AB  - Counting of mitotic cells has been shown to be of prognostic value in breast
      cancer in different retrospective studies. Up to now the number of mitoses is
      assessed mainly manually according to a standardized but strict protocol.
      Although such a manual procedure is reasonably reproducible, automatic counting
      of mitotic cells offers the potential for greater objectivity and
      reproducibility. This paper describes the influence of resolution on automatic
      recognition by image processing of mitotic cells in Feulgen stained breast cancer
      sections. Using the image recording, correction and segmentation procedure
      described in a previous study, five specimens were analyzed: one was used to
      serve as a training set and four were put aside for later use as independent test
      set. For each slide, objects from a pre-selected area were recorded at increasing
      resolution. For each object, contour features and optical density measurements
      were computed and stored in a data file for statistical analysis. The results
      showed that increased resolution using a 40x objective lowered the number of
      misclassified mitoses compared with a 20x objective (overall mean percentage of
      misclassified mitoses over training and all test specimens: 20x, 24.57; 40x,
      7.96). The number of misclassifications of non-mitoses was almost stable per
      specimen but varied between specimens (19-42%) due to differences among tissues.
      Given the improvement in classifying mitoses and the possibility to evaluate
      interactively the measurement result, the described semi-automated mitoses pre
      screener of histological sections may be suitable for further testing in a
      clinical setting.

PMID- 9181304
TI  - Computer-based technique for cell aggregation analysis and cell aggregation in in
      vitro chondrogenesis.
AB  - No quantitative methods are currently available to measure different aggregation
      parameters in cell cultures. In this paper we describe a computer-based technique
      for the automatic and reliable analysis of cellular aggregates, starting from
      optical microscopy images of living cells grown in suspension. The method allows
      determination, on the same sample at different time intervals, of quantitative
      parameters, including aggregation percentage, average number of cells in
      aggregates, and aggregate size statistical distribution. To determine the number
      of cells in an aggregate starting from its two-dimensional microscopic profile, a
      model has been proposed and verified, using sphere packing theory. Algorithms
      have been tested on chondrocyte suspension cultures, where cell aggregation is a
      very early and critical event leading to cell differentiation. Using this
      technique for the analysis of chick embryo chondrocyte cultures, we observed that
      aggregate size and development kinetics depend on the culture conditions used.
      The method, with minor adaptations, is of potential use also in other cell
      systems to evaluate aggregation indexes or to study aggregation kinetics.

PMID- 9181305
TI  - Amount of the two major Ag-NOR proteins, nucleolin, and protein B23 is cell-cycle
      dependent.
AB  - To know the biological basis allowing the use of Ag-NOR protein expression as
      proliferation marker in human malignancies, the relationship between cell cycle
      and amount of Ag-NOR protein was analyzed. The quantification of the two major Ag
      NOR proteins, nucleolin and protein B23, was performed in exponentially growing,
      serum-deprived, and cell-cycle stimulated cells. Expression of nucleolin was low
      in serum-deprived cells and increased mostly in S phase during cell-cycle
      stimulation. Conversely, expression of protein B23 was slightly repressed in
      serum-deprived cells, and increased progressively until G2 phase during cell
      cycle stimulation. The accumulation of nucleolin and protein B23 in G2 compared
      to G1 was demonstrated using sorted phase-specific cells. In G0, cells sorted
      according to their very low RNA content, and the amount of Ag-NOR proteins was
      half of that found in G1 cells, nucleolin being only weakly detectable.
      Therefore, the expression of nucleolin increased between G0-G1 and G1-S phases.
      These data support the hypothesis that quantification of Ag-NOR proteins is an
      estimation of the percentage of cells in each cell cycle phase because their
      amount is high in S-G2 and low in G1 phases.

PMID- 9181306
TI  - Peripheral blood lymphocyte binding to a soluble FITC-fibronectin conjugate.
AB  - Fibronectin receptors are critical to lymphocyte-mediated inflammation, and
      binding between immobilised plasma fibronectin and peripheral blood lymphocytes
      (pbl) is enhanced in patients with inflammatory diseases. Such enhancement could
      be due to an overall increase in receptor capacity and/or be a feature of a
      subset of cells. It could also depend on the initial binding and/or on events
      that follow receptor occupancy (e.g., cell spreading). To address these
      questions, we used fluorescein isothiocyanate-conjugated soluble fibronectin
      (FITC-FN) in a flow cytometric assay of lymphocyte-fibronectin binding. EDTA
      inhibitable adhesiveness to FITC-FN is enhanced in lymphocytes cultured with
      Interleukin 2 and in fresh peripheral blood lymphocytes (pbl) from untreated
      patients with acute exacerbations of chronic inflammatory diseases. The enhanced
      binding was noted on both CD4+ and CD8+ subsets, and decreased with anti
      inflammatory therapy.

PMID- 9181307
TI  - Assessment of amphotericin B susceptibility in Leishmania infantum promastigotes
      by flow cytometric membrane potential assay.
AB  - Flow cytometry was used for measuring the effects of amphotericin B on the
      membrane of Leishmania infantum strains. The technique was adapted from the rapid
      flow cytometric membrane potential assay developed by Ordonez and Wehman
      (Cytometry 22:154-157, 1995) for evaluating antibiotic-susceptibility of Candida
      species. The study consisted of measuring membrane potential changes induced by
      amphotericin B in 3 initial strains and 12 laboratory-generated variants adapted
      to grow with amphotericin B. Results showed that, after 3 h of incubation,
      amphotericin B induced a dose-related decrease of membrane potential that reached
      its maximal level at the same concentrations that inhibited parasite growth.
      These results suggest that the flow cytometric membrane potential assay could be
      used to assess the susceptibility of Leishmania promastigotes to amphotericin B.

PMID- 9181308
TI  - Uptake and efflux of polycyclic aromatic hydrocarbons by Tetrahymena pyriformis:
      evidence for a resistance mechanism.
AB  - The action of benzo(a)pyrene (BP), 3-methylcholanthrene (3MC), benzanthracene
      (BA), and 7,12-dimethylbenzanthracene (DMBA), four polycyclic aromatic
      hydrocarbons (PAHs), was studied on the unicellular protozoan Tetrahymena
      pyriformis. This ciliate was exposed to the PAHs at 1, 15, and 37 microM for up
      to 6 h. BP and BA caused a slight inhibition of cell growth, whereas 3MC and DMBA
      showed no detectable effect. Cell viability remained unaffected by the PAHs at
      all concentrations and exposure times tested. Cellular accumulation of PAHs was
      studied using flow cytometry. The results show immediate accumulation followed by
      rapid elimination of the compounds. BP uptake was also studied in the presence of
      verapamil and cyclosporin, compounds known as inhibitors of the multidrug
      resistance (MDR) pump. In the presence of verapamil, BP was accumulated in larger
      amounts in cells. With cyclosporin, the accumulation of the PAH was several times
      higher than under control conditions. The results of GC/MS analysis show that PAH
      elimination was not linked to biotransformation. These results suggest that the
      resistance of Tetrahymena against PAH cytotoxicity may be attributed to the rapid
      efflux of these agents from the cells via an efflux pump probably of the MDR
      type.

PMID- 9181309
TI  - Variability of DNA analysis by image cytometry. Bladder Tumor Marker Network.
AB  - Two laboratories equipped with CAS 200 (Becton Dickinson Image Cytometry Systems,
      San Jose, CA) instruments participated in this study of variability of DNA
      analysis of bladder tumor specimens. Formalin fixed paraffin embedded specimens
      were disaggregated and centrifuged onto microscope slides from ten bladder tumor
      specimens and two specimens of normal urothelium. Sources of variability
      considered were Specimen, Slide, Run, Laboratory, and Error. Slides were
      systematically scanned and 200 cells measured followed by the operator selecting
      100 nuclei with abnormal morphology. DNA index (DI) and hyperdiploid fraction
      (HDF) were calculated from the DNA frequency distributions. For systematic
      sampling, 92% of the variability was due to Specimen indicating that differences
      in HDF values between specimens reflect biological differences. With selective
      sampling, only 67% of the variability in HDF is due to Specimen differences.
      Other factors, Laboratory, Error, and Laboratory x Specimen interaction each
      accounted for approximately 10% of the variability. Similarly variability of DI
      with selective sampling was also higher, and less specimen dependent than
      systematic sampling. It is important that sampling schemes and selection criteria
      be carefully documented in order to control variability. Enriched (or selective)
      sampling for abnormal cells has the potential to increase sensitivity but
      specimen classification based on these measurements must depend on determination
      of the frequency of such cells in the total population.

PMID- 9181310
TI  - Can academic and nonprofit cytology laboratories survive? Should they?

PMID- 9181311
TI  - Cytopathological variables in parathyroid lesions: a study based on 1,600 cases
      of hyperparathyroidism.
AB  - Fine-needle aspirates and tissue sections from 120 surgically treated parathyroid
      (PT) lesions and histologic archive material from PT lesions in 1,500 additional
      cases of hyperparathyroidism were reviewed to assess the importance of various
      features in distinguishing PT disease from other types of lesions by aspiration
      cytology. We conclude that the morphologic variation shown by PT lesions is so
      many-sided that this distinction cannot be based on the presence or absence of a
      single feature only. Instead the cytologic picture as a whole must be taken into
      account and evaluated with full knowledge of the anatomical conditions pertaining
      to the lesion examined. If still in doubt, the diagnosis can be substantiated by
      supplementary immunocytochemical examinations.

PMID- 9181312
TI  - Fallopian tube cytology: a histocorrelative study of 150 washings.
AB  - The aim of the study was to assess the relationship between fallopian tube lavage
      cytology and recognized microscopic prognostic features in cancer of the uterine
      corpus. Tubal (TW) and peritoneal washing cytology (PW), endometrial tumor grade,
      and tumor involvement of the cervix, myometrium, myometrial vessels, and
      peritoneum were assessed in 150 patients. Endometrioid adenocarcinoma grade I was
      considered a low-grade tumor, while endometrioid carcinoma grades 2/3,
      serous/clear cell carcinoma, carcinosarcoma, and high-grade stromal sarcoma were
      considered high grade. The overall concordance rate for paired TWs and PWs was
      72% (108/150). Forward stepwise logistic regression analysis of the 150 tumors
      revealed that only PWs and cervical involvement were independently predictive of
      TWs. No relationship was evident between TWs and depth of myometrial invasion,
      myometrial vascular involvement, or peritoneal metastases. It is concluded that
      retrograde transtubal spread by malignant endometrial cells occurs independently
      of myometrial histoprognostic features. TWs provide supporting evidence for
      diagnostically difficult PWs, and malignant TWs may be detected in the presence
      of minimally invasive serous/clear cell carcinoma and carcinosarcoma of the
      endometrium.

PMID- 9181313
TI  - Cytologic features of post-transplant lymphoproliferative disorder.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are Epstein-Barr virus (EBV)
      associated lymphoid proliferations which affect approximately 2% of organ
      allograft recipients. Although the histologic features of PTLD are well
      described, they have been described only rarely in cytologic specimens. The
      cytomorphologic features of PTLD in body fluid specimens, needle aspirations, and
      a gastric brushing specimen from seven patients with histologically confirmed
      PTLD were therefore reviewed. In the cytologic specimens, PTLD was characterized
      by a mostly polymorphous population of lymphoid cells containing many large
      transformed lymphocytes, occasional immunoblast-like atypical lymphocytes,
      necrosis, and, frequently, obvious plasmacytoid differentiation. The presence of
      EBV was documented in five of the seven cases in the corresponding tissue
      biopsies. The four patients with PTLD in a body fluid specimen all died within 3
      months of detection of the PTLD in the body fluid. The three remaining patients
      are alive with resolution of PTLD (follow-up of 7, 8, and 14 months). The
      diagnosis of PTLD should be suggested when cytologic specimens from organ
      allograft recipients show a polymorphous atypical lymphoid proliferation,
      frequently with plasmacytoid differentiation and necrosis. Cytologic samples may
      provide the initial diagnosis of this potentially fatal disease and allow
      appropriate intervention. The presence of PTLD in a body fluid specimen is a poor
      prognostic indicator.

PMID- 9181314
TI  - Silver staining method for nucleolar organizer regions in cervical smears.
AB  - The distribution of nucleolar organizer regions (NORs) was studied in
      Papanicolaou preparations of cervical smears in order to distinguish benign from
      preneoplastic lesions. Destained smears (six defined as normal, six as
      inflammatory with squamous metaplasia, six as CIN I, six as CIN II, and five as
      CIN III) were submitted to the Ag-NOR method after staining with Orange G and
      EA36. Ag-NOR count was performed in previously outlined fields on the smears.
      Statistically significant differences (P < .05) were found between the normal
      smears, inflammatory smears with squamous metaplasia, and each grade of CIN. We
      conclude that the Ag-NOR technique could be useful to evaluate cervical smears of
      doubtful interpretation, using previous demarcation of the abnormal fields/cells.

PMID- 9181315
TI  - Excessive formation of basement membrane substance in clear-cell carcinoma of the
      ovary: diagnostic value of the "raspberry body" in ascites cytology.
AB  - Formation of basement membrane-like substance or so-called collagen core was
      characteristic of clear-cell carcinoma of the ovary in ascites cytology. The
      hyaline extracellular material was stained light green in Papanicolaou smears and
      pinkish to purplish red in Giemsa preparations and was frequently observed within
      the cancer cell clusters in all ten samples of clear-cell carcinoma. Such a
      structure termed "raspberry body" was focally seen in one of 30 specimens of
      serous cystadenocarcinoma and one of 30 samples containing reactive mesothelial
      cells. The "raspberry body" was not found in ascitic fluid from ten patients with
      mucinous cystadenocarcinoma and two with endometrioid carcinoma. Overproduction
      of the acidic-charged basement membrane substance was confirmed by 1)
      cytochemical positivity for periodic acid-Schiff, alcian blue (pH 2.5 or pH 1.0),
      colloidal iron, and periodic acid-methenamine silver, 2) immunocytochemical
      demonstration of laminin and type 4 collagen, and 3) ultrastructural
      identification of excessive formation of the basal lamina. Recognition of the
      "raspberry body" helps cytopathologists make a cytologic diagnosis of this
      chemotherapy-resistant malignancy disseminated in ascitic fluid.

PMID- 9181316
TI  - Effectiveness of automated cervical cytology rescreening using the AutoPap 300 QC
      System.
AB  - This study assesses the performance of the AutoPap 300 QC System in identifying
      false-negative (FN) smears in a slide population previously screened as normal
      and compares the detection rate to that achieved with a random rescreen of the
      same slide population. A total of 1,840 "normal" smears were rescreened both
      manually and by the AutoPap 300 QC System. Overall, a total of 7 FN slides were
      detected. At QC selection rates of 30% and 20% the device achieved sensitivities
      for detection of FN smears of 57.19% (4/7) and 42.8% (3/7), respectively. This
      represents a three- to fourfold enrichment in the number of FN smears over that
      obtained by a random rescreen of a similar proportion of cases. None of the FN
      slides were identified by either method at a 10% rescreening rate. The ability of
      the device to detect slides previously classified as abnormal (n = 139) and FN (n
      = 40) was also studied. The overall sensitivity to abnormal smears at QC
      selection rates of 10%, 20%, and 50% was 61.9%, 77.0%, and 94.2%, respectively.
      Improved sensitivity to smears classified as LSIL or worse (n = 112) was obtained
      for corresponding selection rates (61.6%, 75.9%, and 93.8%). Sensitivity to FN
      slides classified as LSIL or worse (n = 17) for QC selection rates of 10%, 20%,
      and 50% was 29.4%, 70.6%, and 88.2%, respectively. The sensitivity and
      specificity of the device to an adequate squamous and endocervical cell component
      was also determined. At predetermined thresholds, the overall sensitivity to
      slides with an inadequate squamous cell component (n = 55) and to those smears
      with an endocervical cell component (n = 1.587) was 81.8%, and 82.7%
      respectively. The study demonstrated that the AutoPap 300 QC System is superior
      to human random rescreen for the identification of FN smears although only a
      marginal improvement was noted due to the small sample. Further studies are
      required using a larger number of smears to fully assess the value of the device
      in quality control mode. The device also has the potential to improve the
      accuracy of specimen adequacy determinations and to serve as a useful adjunct to
      existing quality control measures designed to monitor individual performance and
      reporting accuracy.

PMID- 9181317
TI  - Cytologic characteristics of peripheral neuroectodermal tumors in fine-needle
      aspiration smears: a retrospective study of three pediatric cases.
AB  - Cytologic diagnosis of peripheral neuroectodermal tumors (PNT) on fine-needle
      aspiration (FNA) smears represents a challenge to the cytopathologist. Usually
      ancillary studies are used to achieve definitive diagnosis. We retrospectively
      examined FNA material from three cases of PNT with the aim of identifying their
      features. Positive and negative cytologic findings were recognized. Positive
      features for PNT included the presence of: rather uniform appearance of the
      cells, which display scant but almost always-present perinuclear clear cytoplasm
      (suggesting a bland epithelial tumor); nuclei with distinctively smooth nuclear
      membrane contour, finely granular chromatin, and one or two small nucleoli
      (suggesting neuroendocrine anlage); and organization of the cells singly or in
      cohesive clusters. Negative findings included the absence of: frequent mitotic
      figures, large nucleoli, nuclear pleomorphism, cellular debris, histiocytes, and
      polymorphonuclear leucocytes. The smears appeared clean, with small, uniform
      cells having features suggesting a neuroendocrine epithelial tumor. These
      findings may prove useful for accurate cytologic diagnosis and differentiation of
      PNT from other small blue round cell tumours (SBRCT) of soft tissues without the
      use of ancillary studies since, when properly evaluated, cytomorphology of the
      latter group of tumors is more heterogeneous than generally believed.

PMID- 9181318
TI  - Salivary gland anlage tumor: cytologic features in a case examined by fine-needle
      aspiration.
AB  - The cytologic features in fine-needle aspirates from a rare benign nasopharyngeal
      salivary gland anlage tumor in a newborn boy are described and commented on,
      regarding therapeutically important differential diagnoses.

PMID- 9181319
TI  - Malignant pleural effusions due to adeno-endocrine-cell carcinoma of the
      appendix: a case report.
AB  - The cellular features of adeno-endocrine-cell carcinoma of appendiceal origin are
      presented. The pleural fluid contained metastatic predominantly atypical cells in
      linear cluster accompanied by numerous mesothelial cells. The cells had small
      round nuclei, with a slight tendency to molding; nucleoli were absent. The
      cytologic findings in Papanicolaou-stained smears of the pleural fluid suggested
      a metastatic small-cell carcinoma of the lung. Subsequently, adeno-endocrine-cell
      carcinoma of the appendix was demonstrated at autopsy. Reports of such
      occurrences are few; no study, to the best of our knowledge, has previously
      documented the cytologic diagnosis in pleural fluid.

PMID- 9181320
TI  - Fine-needle aspiration biopsy of salivary duct carcinoma: report of five cases.
AB  - Salivary duct carcinoma is a high grade malignancy which histologically strongly
      resembles ductal carcinoma of the breast. The findings from five cases of
      histologically proven salivary duct carcinoma sampled by preoperative fine-needle
      aspiration (FNA) cytology are presented. Characteristic cytomorphologic features
      include cohesive clusters and flat sheets of epithelial cells which display a
      cribriform pattern with eccentrically located, hyperchromatic nuclei, abundant
      finely granular cytoplasm, and necrosis in the smear background.

PMID- 9181322
TI  - Is there a role for fine-needle aspiration in radial scar/complex sclerosing
      lesions of the breast?
AB  - The fine-needle aspiration cytology (FNA) from 12 mammographically detected,
      histologically confirmed radial scar/complex sclerosing lesions (RS/CSL) and
      their corresponding mammography were reviewed. Six aspirates were obtained by
      palpation, four by ultrasound guidance, and two by stereotactic guidance. Of the
      eight lesions with sufficient material five (62.5%) were reported as benign, two
      (25%) as atypical, and one (12.5%) as suspicious. It is proposed that FNA for
      RS/CSL should not be performed, and lesions require excision for histologic
      assessment.

PMID- 9181321
TI  - Hashimoto's thyroiditis: cytodiagnostic accuracy and pitfalls.
AB  - To determine the cytodiagnostic accuracy rate and pitfalls of Hashimoto's
      thyroiditis (HT), the files and smears prepared from the thyroid needle aspirates
      of 146 patients with suspected HT and/or clinically and serologically confirmed
      HT were reviewed. Of those patients, 105 presented with a diffuse and rubbery
      thyroid enlargement, and 41 with one or two prominent nodules. For the first
      group (105 patients), the needle aspiration biopsy (NAB) was performed on one or
      two thyroid lobes during their initial endocrinologic consultation, and for the
      second group (41 patients), the NAB was performed on and around the predominant
      nodules that were found either at initial physical examination or during the
      patients' routine follow-ups. In 134 cases, a cytodiagnosis of HT was made on the
      first NAB. Among the 41 patients with a prominent thyroid nodule, a thyroid
      neoplasm was suspected clinically in four because their thyroid nodules increased
      in size. In the other 12 patients, a cytodiagnosis of follicular neoplasm (FN)
      was made in five cases, and a Hurthle cell tumor (HCT) was diagnosed or suspected
      in seven patients. All 16 patients had thyroid surgery, and a HT was
      histologically confirmed in all cases. In the first four patients, no tumor was
      found. Among five patients with a cytodiagnosis of FN, one had a hyperplastic
      follicular cell nodule (HFCN), two had follicular adenomas, and two had papillary
      carcinomas of follicular variant. For the seven patients with a cytodiagnosis of
      HCT, HCT was confirmed in three, three were found to have hyperplastic Hurthle
      cell nodules (HHCN), and one showed a benign colloid nodule with Hurthle cell
      changes and remote hemorrhagic necrosis. It is concluded that NAB is highly
      sensitive in diagnosing HT, with a diagnostic accuracy rate of 92% by the first
      biopsy attempt. The cytologic differential diagnosis between an HFCN and a
      follicular neoplasm and between an HHCN and an HCT is impossible in some cases.

PMID- 9181323
TI  - Riu's stain and the cytologic diagnosis of thyroid fine-needle aspiration: a
      single cancer center experience.
AB  - Riu's stain, a Romanowsky-type stain, has been in use in Taiwan over the past 40
      years. In order to determine whether it is useful for the diagnosis of thyroid
      disease in thyroid fine-needle aspiration, we reviewed 254 of these aspirates
      obtained between April 1990 and June 1996 from patients seen in Koo Foundation
      Sun Yat-Sen Cancer Center in Taipei. Surgical follow-up was available for
      confirmation in 61 aspirations. The cytologic diagnosis was categorized into four
      groups: benign, 174; suspicious, 30; malignant, 41): and inadequate specimen, 9.
      There were two false-negative and no false-positive diagnoses. Our results showed
      a sensitivity of 93.5% and a specificity of 100% for the detection of malignancy.
      If suspicious cases were considered positive, the specificity decreased to 55%,
      while the sensitivity increased to 95%. We conclude that Riu's stain is a
      reliable quick stain in the diagnosis of thyroid malignancy. Compared to
      Papanicolaou stain, it shortens the time needed for a cytopathologist to reach a
      diagnosis. Papanicolaou stain can be reserved for confirmation.

PMID- 9181324
TI  - Exfoliative cytology of papillary serous adenocarcinomas of the uterine cervix.

PMID- 9181325
TI  - FNA biopsy diagnosis of HCC.

PMID- 9181326
TI  - Analysis of accommodation function with ultrasonography.
AB  - The aim of this study was to present a new method that uses ultrasonography to
      analyse accommodation function, and to do a preliminary investigation of its
      possible use in clinical practice. Using the method of continuous
      ultrasonographic biometry, changes in lens thickness were measured during
      accommodation. From these measurements response latency and duration were
      determined. Normal values for latency and duration were obtained by measuring 20
      healthy subjects of different ages. Measurements were also performed on three
      patients with different accommodation disorders: diabetes, Adie's syndrome and
      third nerve palsy. Normal response latency is 394 ms (+/-46 SD) and independent
      of are. Normal response duration increases with age from an average 306 ms at 15
      years-of-age to an average 954 ms at 55 years-of-age. Normal latency as well as
      duration appear to have a large interindividual variability. The diabetic patient
      had a delayed latency but a normal response duration. The patient with Adie's
      syndrome had a delayed latency and prolonged duration. The patient with third
      nerve palsy had a normal latency and duration. We conclude that
      ultrasonographically determine latency and duration give additional information
      on accommodation function that is more complete and objective than maximum
      accommodative amplitude alone. The results in our patients suggest that, in
      selected cases, this information may aid in the diagnosis and management of
      patient's complaints.

PMID- 9181327
TI  - Cataract surgery and anticoagulants.
AB  - A questionnaire was sent to 240 members of the Netherlands Intraocular Implant
      Club (NIOIC) to register their policy followed in 1993 with regard to
      anticoagulant therapy (ACT) and the use of aspirin in patients having cataract
      surgery. Ninety-one (32%) forms were suitable for analysis. Most eye surgeons
      (76%) declared to discontinue anticoagulant therapy and the use of aspirin prior
      to cataract surgery, especially when using local anesthesia. After stopping
      anticoagulant therapy and the use of aspirin serious systemic complications were
      reported. Furthermore, ocular complications were reported due to continuation of
      ACT and the use of aspirin during surgery. Although the response rate to the
      enquiry was 32% only, we would suggest that continuation of ACT and the use of
      aspirin during surgery is to be recommended because of the possible life
      threatening complications related to discontinuing ACT and the use of aspirin.
      Risks of bleeding can be minimized further by using topical anesthesia, sub-tenon
      anesthesia and clear corneal surgery.

PMID- 9181328
TI  - Effect of interferon-alpha on MHC expression and influx of inflammatory cells on
      the rat eye.
AB  - Interferon-alpha can be used as additional treatment of herpes keratitis.
      However, several studies have demonstrated that interferon-alpha can induce
      immunological changes in several tissues, and if used in a patient with a corneal
      transplantation, those changes might induce rejection of the corneal transplant.
      In order to determine the immunological changes in corneal tissue, we examined
      the effect of local treatment with interferon-alpha on MHC Class I and II
      expression, and inflammatory cell influx in the rat eye, and compared this with
      the changes induced by intrastromal sutures. These changes were evaluated by
      immunohistology for MHC Class I and II and several immunologically active cells.
      Intrastromal sutures induced an influx of lymphocytes and macrophages and
      induction and/or upregulation of MHC Class I and II. Local treatment with
      interferon-alpha did not have any of these effects. We conclude that topical use
      of interferon-alpha is not likely to induce rejection of a corneal graft.

PMID- 9181330
TI  - Posterior segment eye-surgery in day care?
AB  - Day care is generally accepted in anterior segment eye-surgery. In the Rotterdam
      Eye Hospital this option was also considered for posterior segment surgery. We
      were interested in the opinion of patients on this matter and therefore asked
      patients, who were admitted for posterior segment eye-surgery, to answer a
      questionnaire. The major question was: 'If your physician had given his
      permission, do you think it would have been possible for you to go home on the
      evening after surgery?'. Other questions evaluated problems in organising
      assistance at home and transportation to the out-patient clinic as well as
      circumstances after the operation, such as pain, nausea, dizziness and anxiety.
      Eighty-one out of 87 patients responded: 56% answered 'eye' and 44% 'no' to the
      major question. Relating the answer to the major question to medical data and to
      answers to the other questions, we found organizational problems at home and
      anxiety to have a statistical significant relation with a negative answer.
      Clinical factors like age, American Society of Anesthesiologists (ASA)-class,
      diabetes mellitus (including insulin-dependant), type of anesthesia, time of the
      day the surgery was finished, duration of surgery, pain, nausea or dizziness were
      not significantly related. The number of patients involved in this study,
      however, is too small to draw conclusions on specific subgroups of patients.

PMID- 9181329
TI  - Iris-Claw intraocular lenses in children.
AB  - 27 children (38 eyes) with cataracts of different origins were treated using iris
      fixated one-piece Iris-Claw intraocular lenses. Visual acuities outcome in this
      group was comparable with the results in other series. The Iris-Claw lens is a
      very versatile IOL, which can be used in most cataract procedures, it can be
      removed and exchanged with minimal surgical trauma; therefore it is an effective
      modality in correction of the developmental changes in the refraction of the very
      young and growing, aphakic eye.

PMID- 9181332
TI  - Cysteamin eyedrops in three patients with nephropathic cystinosis.

PMID- 9181333
TI  - Vitreous haemorrhage and other ocular complications of a persistent hyaloid
      artery.
AB  - PURPOSE: To report ocular complications of a persistent hyaloid artery. METHODS:
      We studied eight patients with persistent hyaloid artery. RESULTS: Seven patients
      showed strabismus and very low visual acuity (< or = 0.12) of one eye. Despite
      correction of refractive errors, cataract surgery and occlusion therapy for
      amblyopia, visual acuity had not improved in these cases. Four patients showed
      nystagmus. Four had progression of unilateral cataract. In two cases, a 24-year
      old women and a 4-months-old boy, a vitreous haemorrhage had occurred due to
      rupture of a hyaloid artery, in the woman's case probably due to a spontaneous
      posterior vitreous detachment. CONCLUSION: A persistent hyaloid artery may be
      associated with strabismus, cataract, amblyopia and nystagmus. Despite amblyopia
      treatment, the prognosis of visual acuity of the involved eye is unfavourable. A
      persistent hyaloid artery may cause vitreous haemorrhage.

PMID- 9181331
TI  - A retrospective analysis of heparin-surface-modified intraocular lenses versus
      regular polymethylmethacrylate intraocular lenses in patients with uveitis.
AB  - BACKGROUND: Several studies described the benefits of the heparin-surface
      modified intraocular tens (HSM IOL) with regard to the reduced inflammation in
      routine extracapsular cataract extractions. However, limited information is
      available about the advantages of the HSM IOL in patients with an intraocular
      inflammation. AIM: To assess the eventual benefits of the HSM IOL compared to the
      regular polymethylmethacrylate intraocular lens (PMMA IOL) in patients with
      uveitis. METHODS: A retrospective study of 43 patients with uveitis of various
      origins who underwent an extracapsular cataract extraction (24 with HSM, 19 with
      PMMA IOL). The activity of intraocular inflammation, visual acuity, eventual
      complications, and medications were examined. Standardized follow-up dates were
      used (before surgery, one and fourteen days, five and eleven months after
      surgery.) RESULTS: No difference in the inflammatory, activity was noted between
      HSM and PMMA groups; neither at short term clinical evaluation, nor at five
      months after surgery. Despite a slightly better visual acuity in the HSM group
      before surgery, no long term differences were observed. After surgery the
      increase in visual acuity was similar for both groups, as well as the frequency
      of cystoid macular oedema (CMO) and synechiae. Fewer patients in HSM group
      required Nd:YAG posterior capsulotomy, but the difference was not significant.
      CONCLUSION: No clinical advantage was found when the HSM IOL was compared with
      the regular PMMA IOL in 43 patients with uveitis.

PMID- 9181335
TI  - Quantification of the dosage of mitomycin in trabculectomy by the 'mito-pill'.

PMID- 9181334
TI  - Visual acuity and scar size in eyes with age-related subfoveal choroidal
      neovascular lesions, 30 months after radiation therapy.
AB  - PURPOSE: In a study to determine the effectiveness of ionizing radiation on the
      deterioration of visual acuity (VA) due to choroidal neovascularisation (CNV) the
      affected eyes of 10 patients were treated with a total dose of 24 Gy (6 Gy
      fractions). A special lens-sparing technique was used to avoid cataract
      development. During 30 months of follow-up the visual acuity (VA) and scar size
      (SS) of the treated eyes and fellow eyes of all 10 patients were evaluated.
      RESULTS: After 30 months of follow-up 5 eyes showed a stable VA and fluorescein
      angiogram (FA) appearance. Concerning 4 out of 5 eyes with progressive disease,
      the 4 eyes treated with radiation therapy had better VA and smaller SS as
      compared with the untreated fellow eyes with exudative AMD. CONCLUSIONS: The
      results suggest that 24 Gy either stabilizes or delays the deleterious effects of
      CNV on the visual acuity. Until now no late side effects have been observed.

PMID- 9181337
TI  - Cyanoacrylate glue treatment for persistent aqueous leak following
      postkeratoplasty relaxing incisions with compression sutures.
AB  - In spite of improvements in surgical techniques, donor materials and
      postoperative care, high astigmatism remains a quite common problem following
      penetrating keratoplasty [1]. Whenever the residual astigmatism cannot be
      corrected with spectacles or contact lenses, surgical treatment is required.
      Relaxing incisions combined with compression sutures is one of the most common
      methods used for this purpose [2, 3]. We report herein a case of persistent
      aqueous leak following relaxing incisions for the correction of postkeratoplasty
      astigmatism. The leak failed to respond to a bandage contact lens and resuturing
      and was eventually successfully treated with the use of cyanoacrylate glue. A
      marked regression of the surgical effect was observed in this case.

PMID- 9181336
TI  - Contrast sensitivity function after cataract extraction and intraocular lens
      implantation.
AB  - Divergent contrast sensitivity findings have been reported in patients with
      intraocular lens implants. The purpose of this study was to determine contrast
      thresholds of patients with good visual acuity after uncomplicated cataract
      extraction and posterior chamber conventional IOL implantation. Fifty-two eyes of
      fifty two patients, who had undergone uncomplicated extracapsular cataract
      extraction and posterior chamber intraocular lens implantation together with 48
      eyes of 48 control subjects were tested for contrast sensitivity function. All of
      the patients had best corrected visual acuity 0.8 (20/25) or better, on the
      Snellen scale. Patients with concomitant eye disease were excluded. Contrast
      sensitivity was measured using stationary sine-wave gratings of four spatial
      frequencies (3.0 to 18.0 cycles/degree), at the testing distance of 8 feet. A
      loss of contrast sensitivity was found in patients with intraocular lens
      implants, compared with control subjects of similar age, sex and visual acuity.
      The loss was statistically significant at intermediate (6 cyc/deg) and high
      spatial frequencies (12.0 and 18.0 cycles/degree), while it was not statistically
      significant at low spatial frequencies (3 cyc/deg). This may be the reason of
      nonspecific visual complaints ('washed-out images'), despite normal Snellen
      acuity, after cataract surgery and monofocal IOL implantation.

PMID- 9181338
TI  - Conjunctivodacryocystorhinostomy with Jones tube. A 10-year study.
AB  - One hundred and eight patients (111 eyes) underwent
      conjunctivodacryocystorhinostomy with a Jones tube for treatment of epiphora
      resulting from canalicular obstruction. Sixty-nine patients (63.9%) were females
      and thirty-nine (36.1%) were males. Their ages ranged from 9 to 64 years, the
      mean age being 30.1 years. The causes of lacrimal drainage abnormalities included
      idiopathy (76 cases, 68.5%), trauma (15 cases 13.5%), tumors (8 cases, 7.2%)
      congenital abnormalities (6 cases, 5.4%) and conjunctival inflammation (6 cases,
      5.4%). Twenty-eight (36.8%) eyes in the idiopathic group had previous failed
      dacryocystorhinostomies. The operation was successful in 90.1% of the eyes with
      relief of epiphora. Fifty-one out of 111 (45.9%) eyes had complications.
      Extrusion of the tube was the most frequent complication occurring in 20 (18%)
      eyes. Malposition (12 eyes 10.8%), infection (12 eyes, 10.8%) and obstruction of
      the tube (7 eyes, 6.3%) were the other major complications. Of the 20 eyes with
      tube extrusion, 11 experienced recurrent tube losses. Five of 11 eyes were free
      of epiphora after tube loss. Four out of five had the tube in place for 2 to 5
      years and one had the tube, in place for one year. The remaining 6 eyes which had
      the tubes for 6 months to 3 years were complicated by epiphora. Our experience
      confirms the general belief that the tube should stay in place forever. The large
      majority of our patients could wear their tubes successfully and have done so in
      our practice for as long as 10 years.

PMID- 9181339
TI  - Complications following two methods of posterior chamber intraocular lens
      suturing.
AB  - The aim of this study is to compare complication rates in two different operative
      techniques applied for the secondary, posterior chamber intraocular lens (PCIOL)
      implantation with sulcus fixation. 179 eyes with partial or no posterior capsule
      support underwent surgery. Applied techniques were: transscleral fixation of the
      IOL by passing with the fixation needle through the sulcus from the inside (70
      eyes) or from the outside (109 eyes) of the bulbus. The most frequent
      intraoperative complications were haemorrhages and vitreous prolaps with no
      significant difference between used techniques. In the 'from the inside' group,
      following late postoperative complications developed: astigmatism of > 4D (24%),
      cystoid macular oedema (20%), pupil distortion (14%), partial posterior capsule
      opacification (10%), suture exposure (10%), IOL decentration (8%) and
      hemophthalmus (3%). In the 'from the outside' group same complications showed a
      decreased rate: 17%, 16%, 8%, 8%, 9%, 5% and 1%, respectively. Other late
      complications like high intraocular pressure, synechiae and uveitis were
      adequately represented in both techniques. After 24 months follow-up, best
      corrected visual acuity > or = 0.8 was achieved in 48.5% of eyes when 'from the
      inside' and in 57.7% of eyes when 'from the outside' technique was used.

PMID- 9181340
TI  - Evidence for heterogeneity in a small squamous cell type ('light' cells) in the
      rabbit corneal epithelium--a scanning electron microscope study. Corneal
      epithelial squamous cells.
AB  - The rabbit corneal epithelial surface, as viewed by scanning electron microscopy
      (SEM), is composed of a mosaic of polygonal cells with different appearances
      (light, medium and dark) with the lighter cells having a characteristically high
      density of microplicae. From the central zone of the corneal epithelial surface
      of 16 female New Zealand White rabbits (2 kg), the lighter-appearing cells had an
      average area of 108 +/- 47 microns2 (n = 567, +/-SD). A subgroup of atypical
      lighter cells had an average area of 294 +/- 67 microns2 (n = 53) compared to
      typical light cells of 88 +/- 12 microns (n = 514). These atypical lighter cells
      had fused microplicae at their periphery (instead of a uniform arrangement of
      densely packed microplicae), tended to be rounder in shape (as opposed to being
      angular), could show signs of desquamation and were not decorated with the
      epithelial craters found on almost all (92%) other light cells. All of these
      features are suggestive of these atypical lighter cells being the terminal
      phenotype of the light cells just prior to desquamation from the ocular surface.
      The observation of the desquamation of lighter cells supports a hypothesis that
      they constitute a distinct sub-population of cells at the corneal epithelial
      surface.

PMID- 9181341
TI  - Towards a universal approach for screening of retinopathy of prematurity (ROP).
AB  - To improve the cost-benefit ratio of our current screening program for
      retinopathy of prematurity (ROP), the records of 312 infants who had been
      screened for ROP were studied retrospectively. Using a safety-index containing
      three well known risk factors (birthweight, gestational age, oxygen use), infants
      were classified to be at high risk or low risk for the development of ROP. When
      all high risk infants would have been screened extensively from the 5th postnatal
      week onwards and all low risk infants would have been screened once at the 7th
      postnatal week, a 9.8% reduction of ophthalmological examinations would have been
      obtained at the expense of missing 2.9% of non vision threatening ROP.

PMID- 9181342
TI  - Correlation of an exercise-induced increase in systemic circulation with neural
      retinal function in humans.
AB  - Although the effects of physical exertion on intraocular pressure and systemic
      blood pressure are well established, the retinal response to such physiologic
      stress has not been examined. We studied the effect of short-term intense
      exercise on the principal waves in the scotopic and photopic flash
      electroretinograms, as well as the lower-amplitude oscillatory potentials.
      Sixteen healthy volunteers between 20 and 30 years of age participated in this
      experiment. The electroretinograms and oscillatory potentials were recorded with
      a Nicolet CA-1000 clinical averager, using DTL-type fiber electrodes. All retinal
      potentials were taken immediately before and after a minimum 20-min period of
      stationary bicycling that increased the heart rate to about 140 beats per minute.
      The electroretinograms were recorded from eyes with dilated pupils, 10 min after
      white-light adaptation of the right eye, and 30 min after dark adaptation of the
      left eye. Red flashes and dim white flashes were used to elicit photopic and
      scotopic electroretinograms, respectively. While no changes were recorded for any
      of the electroretinogram components recorded under photopic conditions, the
      amplitude of OP5 was decreased and the implicit time of OP4 was delayed after
      exercise for scotopic conditions. We concluded that exercise caused component
      specific changes in the scotopic oscillatory potentials. Since it is well known
      that oscillatory potentials are vulnerable to ischemia, scotopic oscillatory
      potentials may be used as simple noninvasive indices of the reactivity of the
      retinal vascular autoregulatory system during exercise.

PMID- 9181343
TI  - On- and off-responses in the photopic electroretinogram in complete-type
      congenital stationary night blindness.
AB  - We examined the on- and off-responses of the photopic electroretinogram in
      patients with complete congenital stationary night blindness. Standard flash
      electroretinograms as well as those produced in a ganzfeld modified for long
      duration light stimuli (500 msec) permitted the separation of on- and off
      responses in four patients and four normal subjects. The amplitude and latency of
      the elctroretinogram on-response (a- and b-waves) and off-response (d-wave) in
      addition to the oscillatory potentials of the off-response in normal subjects and
      patients were compared. The abnormal on-response was demonstrated in all the
      patients, and the off-response with its oscillatory potentials were preserved. We
      showed that the second portion of the off-response (of inner retinal origin) is
      normal. If congenital stationary night blindness is a defect of depolarizing
      bipolar cells, these results preclude input of the depolarizing bipolar cells and
      support the hyperpolarizing bipolar cells as the cellular origin of the off
      response electroretinogram.

PMID- 9181344
TI  - Normal electro-oculograms in two patients with malignant melanoma of the choroid.
AB  - The electro-oculogram has been applied in the diagnostic evaluation of eyes with
      malignant uveal melanoma. Typically, a marked reduction in the light peak to dark
      trough ratio has been reported. We studied two patients with histologically
      confirmed uveal malignant melanomas in whom the preenucleation electro-oculograms
      were normal. The electro-oculogram should be evaluated within the framework of
      the clinical examination and other ancillary tests in the diagnostic evaluation
      of a suspected uveal malignant melanoma.

PMID- 9181345
TI  - Cone-rod dysfunction in patients with unexplained reduction in visual acuity.
AB  - Electrophysiologic tests were performed in 233 patients who complained of reduced
      visual acuity with no satisfactory clinical explanation. The functional integrity
      of the retina was assessed from the light- and dark-adapted electroretinogram.
      Macular function and conduction in the optic nerves were estimated from the flash
      visual evoked potentials. Of the 233 patients 78 were grouped together on the
      basis of the electrophysiologic and clinical findings. They were characterized by
      subnormal electroretinogram responses with the cone system more affected than the
      rod system. The flash visual evoked potential responses were of abnormal waveform
      and prolonged implicit times. Most of these patients exhibited normal fundi. The
      reduction in visual acuity, the degree of electroretinogram deficits and the
      pattern of the visual evoked potential responses were similar in both eyes of
      each patient, indicating a symmetric disorder. Slight deterioration of visual
      acuity and electrophysiologic variables were observed in 37 of the patients who
      were followed up over a period of up to 8 years. The electrophysiologic findings
      indicate that about 20% of patients complaining of unexplained reduction in
      visual acuity were suffering from a diffuse retinal disorder affecting the
      peripheral retina as well as the macular region. On the basis of
      electrophysiologic findings and clinical symptoms, we suggest grouping these
      patients under a new entity: cone-rod dysfunction.

PMID- 9181347
TI  - Color-coded pattern suppresses visual evoked cortical potentials and
      electroretinograms.
AB  - We developed a new visual stimulating system for recording visual evoked cortical
      potentials and electroretinograms. The stimulus was a color checkerboard, in
      which each check kept its chromaticity but changed its luminance with its
      corresponding check. Color-coded pattern stimuli using red and green checks did
      not produce visual evoked cortical potentials, while yellow checks produced clear
      responses in a normal subject. Moreover, five color stairs from red and green to
      yellow showed only that the more colors are different, the smaller the visual
      evoked cortical potentials become. In addition electroretinogram recordings
      indicated that color-coded patterns behave in the same way as in visual evoked
      cortical potentials. The mechanism that causes the small color visual evoked
      cortical potentials may already be present in the retina. Color perception may be
      able to induce a suppression of responses for luminance contrast that appears to
      be formed already in the retina. Retinal responses were affected whether the
      stimulus field was color coded or not. Pattern electroretinograms appear to be
      more than the sum of local on and off responses.

PMID- 9181346
TI  - Check size tuning of the pattern electroretingoram: a reappraisal.
AB  - The pattern electroretinogram was recorded to checkerboard stimuli with a wide
      range of check sizes and two stimulus field sizes. Check sizes ranged from 0.25
      degree to 7 degrees (field size, 16 degrees x 14 degrees) and 0.25 degree to 15
      degrees (field size, 32 degrees x 27 degrees) in 14 and seven subjects,
      respectively. Reversal rate was 4.5/s. For minimal intrusion of blink artifacts
      the interrupted stimulation technique was employed. The P50 and N95 components of
      the pattern electroretinogram were evaluated separately. With both stimulus field
      sizes amplitude of P50 and N95 was maximal between 0.75 degree and 1 degree. With
      smaller check sizes the amplitude dropped monotonically. With larger check sizes
      field size played a role: with the 16 degrees x 14 degrees field, P50 gradually
      dropped to 89% from 1 degree to 7 degrees, which was paralleled by N95 only up to
      7 degrees, where N95 dropped to 81% (p < 0.05). With the 32 degrees x 27 degrees
      field, there was no significant difference in size dependency between P50 and N95
      for large check, both components staying constant from 1 degree to 15 degrees. We
      conclude that there is only minor large-check attenuation of the pattern
      electroretinogram, especially with a large field. The apparent field-size
      dependency may explain previous discrepancies in the literature.

PMID- 9181348
TI  - Motion-onset visual evoked potentials improve the diagnosis of glaucoma.
AB  - Chronic glaucoma has been shown preferentially to damage larger retinal cells and
      optic nerve fibres that provide the input to the magnocellular visual pathway. We
      compared the motion-onset visual evoked potentials (primarily the magnocellular
      system) with those to standard pattern reversal in 20 patients with bilateral
      chronic glaucoma. For motion-onset visual evoked potentials, the pattern
      (isolated 40' checks of 10% contrast) moved in four cardinal directions (varied
      randomly from trial to trial) at a velocity of 10 deg/s for 20 ms, with an
      interstimulus interval of 1 s. In pattern-reversal stimulation, the checkerboard
      reversed at a rate of 2 reversals per second. In 60% of the eyes investigated,
      the results of both types of visual evoked potentials correlated, showing either
      normal (27.5%) or increased (32.5%) latencies. In the remaining 40% of the eyes,
      the normal pattern-reversal visual evoked potential latencies were accompanied by
      prolonged motion-onset visual evoked potentials. The high occurrence of delayed
      motion-onset visual evoked potentials in our patients confirms the primary
      magnocellular loss in chronic glaucoma and suggests that the motion-onset VEPs
      are suitable for detection of glaucomatous changes.

PMID- 9181349
TI  - The prognostic value of visual evoked response latency in the treatment of
      amblyopia caused by strabismus.
AB  - Visual evoked response alterations and especially P100 latency were studied in 60
      patents with amblyopia caused by strabismus. Patients were divided in two groups
      according to the mode of fixation of the strabismic eye. Group A included
      patients with eccentric fixation, and group B, patients with central fixation of
      the strabismic eye. In all cases visual evoked responses were recorded before and
      after a 6-month period during which the patients had full-time occlusion of the
      sound eye. In cases with eccentric fixation of the strabismic eye, P100 latency
      was more abnormal than in cases with central fixation. In cases where latencies
      are clearly abnormal before treatment, the prognosis is poor and the results
      after occlusion of the sound eye are unstable. In contrast, in the cases with
      normal or nearly normal visual evoked response latencies, the prognosis is
      better, and these eyes show satisfactory improvement of visual acuity.

PMID- 9181350
TI  - Effects of mitomycin C on the rat retina.
AB  - To evaluate the retinal toxicity of mitomycin C injection in the rat eye, we
      conducted an electroretinographic study and a histopathologic study. Three
      different concentrations of mitomycin C (0.2, 0.3 and 0.4 mg/ml) were injected
      into either the vitreous cavity or the anterior chamber of the experimental eyes.
      A full-field electroretinogram was recorded before injection and 2, 4 and 7 days
      after injection. The retinas of all eyes were examined by light and electron
      microscopy. We found no evidence of electroretinographic and histologic changes 2
      and 7 days after injection of 0.4 mg/ml of mitomycin C into the anterior chamber.
      However, profound electroretinographic changes did follow injection of the drug
      into the vitreous. These were absent with the 0.2-mg/ml solution at 7 days, mild
      with the 0.3-mg/ml solution at 7 days and profound with the 0.4-mg/ml solution as
      early as 2 days. Intravitreal injection of 0.4 mg/ml, however, showed selective
      degeneration of Muller cell process at day 2, retinal pigment epithelium changes
      at day 4 and irregular arrangement of the outer nuclear layer and photoreceptors
      at day 7. Intravitreal injection of mitomycin C in a concentration comparable to
      the one used clinically could cause retinal disorders, both functionally and
      histologically.

PMID- 9181351
TI  - Electrode standards in electroretinography.

PMID- 9181352
TI  - Empirical genomewide significance levels established by whole genome simulations.
AB  - The advent of high-resolution genetic maps and semiautomated genotyping
      technology has opened the way for genome screening in genetically complex traits.
      Many such screens are now under way, or completed, most using multipoint
      nonparametric linkage analysis of affected sibling pairs. This type of linkage
      analysis uses all the available genotype information to calculate the maximum lod
      score (MLS) value at each point in the genome, and thereby generates MLS profiles
      along each chromosome. Any positive MLS values indicate potential linkage, but
      the peaks in these profiles, which may be referred to as "hits," identify the
      most likely locations of disease susceptibility genes. However, such analysis
      presents serious problems of multiple testing, and the assessment of the
      statistical significance of hits has become a contentious issue [Lander and
      Kruglyak (1995) Nat Genet 11:241-247; Curtis (1996) Nat Genet 12:356-357; Witte
      et al. (1996) Nat Genet 12:355-356]. Having recently completed a genome screen in
      multiple sclerosis, we decided to investigate the statistical properties of our
      study by simulation. We report here in detail the results of this simulation
      study. Our main conclusion is that, for the particular set of families and
      markers used in our screen, an MLS of 3.2 carries a genome-wide significance of
      5% (that is, there is a 5% probability of observing at least one false hit, above
      this threshold in a complete genome screen). This value is closer to the familiar
      limit of 3.0, originally suggested by Morton [1955; Am J Hum Genet 7:277-318]
      than to the more stringent limit of 4.0 recently proposed by Lander and Kruglyak
      [1995; Nat Genet 11:241-247]. This is somewhat reassuring, in view of the very
      large sample sizes that would be necessary to achieve adequate power to detect
      linkage at the more stringent threshold.

PMID- 9181353
TI  - Transforming growth factor alpha locus and nonsyndromic cleft lip with or without
      cleft palate: a reappraisal.
AB  - An association between nonsyndromic cleft lip with or without cleft palate (CL +/
      P) and genetic variation at the transforming growth factor alpha (TGFA) locus
      was originally reported in 1989. Subsequent population-based studies of this
      association have provided conflicting results. The present analyses were
      undertaken to determine if the cumulative weight of the available data
      convincingly supports or refutes this association. The published data were
      analyzed for differences in allele frequencies between Caucasian CL +/- P
      patients (i.e., cases) and controls, and for heterogeneity between Caucasian
      samples. When all data except the original report were considered, there was a
      statistically significant association between TGFA and CL +/- P (M.H.O.R. = 1.43;
      95% C.I. 1.12-1.80). However, there was evidence of significant heterogeneity in
      the TGFA allele frequencies between cases, but not controls, from different
      studies. The data suggest that the observed heterogeneity is unlikely to be
      attributable to differences in the ethnic composition of the cases among the
      various studies but may reflect differences in the proportion of cases with
      bilateral lip defects and/or with positive family histories of CL +/- P.
      Definitive conclusions regarding the source(s) of the observed heterogeneity
      could not, however, be drawn on the basis of the available data. Hence, at
      present, the evidence regarding an association between genetic variation at the
      TGFA locus and CL +/- P remains inconclusive.

PMID- 9181354
TI  - Heritability of factors of the insulin resistance syndrome in women twins.
AB  - The insulin resistance syndrome (IRS) is characterized by a combination of
      interrelated coronary heart disease (CHD) risk factors, including low high
      density lipoprotein cholesterol (HDL-C) levels, obesity and increases in
      triglyceride (TG), blood pressure, small low-density lipoprotein particles (LDL),
      and both fasting and postload plasma insulin and glucose. Using factor analysis,
      we previously identified 3 uncorrelated factors that explained 66% of the
      variance among these variables, based on data from women participating in
      examination 2 of the Kaiser Permanente Women Twins Study in Oakland, CA during
      1989-1990. The factors were interpreted as: 1) body mass/fat distribution, 2)
      insulin/glucose, and 3) lipids: TG, HDL-C, LDL peak particle diameter. In this
      analysis, heritability of each of the factors was estimated based on data from
      140 monozygotic and 96 dizygotic pairs of non-diabetic women twins. Heritability
      estimates were calculated using the classical approach, the analysis of variance
      (ANOVA) approach, and the maximum likelihood approach. For the body mass/fat
      distribution factor heritability estimates suggest moderate genetic influences;
      0.61 (P < 0.001), 0.14 (P > 0.05), and 0.71 (P < 0.001), respectively. The
      insulin/glucose factor appeared to be highly heritable, with estimates of 0.87,
      0.92, and 0.57 (all P < 0.001), respectively. The heritability estimates for the
      lipid factor were moderate and consistent across methods: 0.25 (P < 0.10), 0.32
      (P < 0.05), and 0.30 (P < 0.05), respectively. These results are consistent with
      genetic influences on each of the 3 "factors," and suggest that both genetic and
      environmental effects are involved in the clustering of IRS risk factors.

PMID- 9181355
TI  - Heritability of plasma leptin in a population sample of African-American
      families.
AB  - The aim of this study was to examine familial patterns of plasma leptin levels
      and the potential association with cardiovascular risk factors in a population
      sample of African-American families recruited from metropolitan Chicago. The
      study included 68 mothers, 31 fathers, 143 daughters, and 119 sons, for a total
      of 361 individuals from 118 families. Leptin levels were adjusted for the effect
      of age separately for mothers, fathers, daughters, and sons. Residuals were then
      standardized before estimating familial correlation using the maximum-likelihood
      method available in SEGPATH. With the exception of height, plasma leptin level
      was strongly correlated with all measured anthropometric variables. Familial
      effect (i.e., heritability) of leptin levels was estimated as 39% in this
      population at high risk for over weight. A significant sex difference was
      observed, and most of the estimated familial effect may be attributed to genetic
      influences since the spouse correlation was not statistically different from
      zero. A strong nonshared environmental effect is also suggested, however.

PMID- 9181356
TI  - Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are
      associated with fasting lipid and lipoprotein traits in a population sample from
      Iceland: interaction between genotype, gender, and smoking status.
AB  - The effects of polymorphisms in the lipoprotein lipase (LPL) gene (HindIII and
      S447X) and in the apolipoprotein (apo) AI-CIII gene cluster (G75A and C1100T) on
      levels of fasting plasma triglycerides, apoCIII, high density lipoprotein
      cholesterol (HDL-C), and apoAI were examined in 315 healthy men and women from
      Iceland. Non-smoking and smoking men and women were examined separately because
      of the strong effects of smoking status and gender on lipoproteins. For the LPL
      gene, there were no significant associations between plasma traits and genotypes
      of the S447X polymorphism, but the LPL-HindIII polymorphism was associated with
      significant effects on levels of all traits, with the effect of genotype on
      triglycerides and apoAI being modulated by smoking status, (genotype x smoking
      interaction, P < .02). The H- allele was generally associated with slightly lower
      levels of apoCIII, with a lowering effect on triglycerides only in smokers and
      with a raising effect on ApoAI in non-smoking and smoking men and in non-smoking
      women. For the apoCIII C1100T polymorphism, smoking and non-smoking men with one
      or more T alleles had levels of triglycerides roughly 10% higher than those with
      only the C allele; in contrast, the women with the T allele had lower levels of
      triglycerides (15.7% lower in non-smokers, P = .04; gender x genotype
      interaction, P = .02). In males and females and in smokers and non-smokers, the T
      allele was associated with levels of apoCIII that were 9-20% higher than those
      with only the C allele (P = .004 overall). In the non-smoking men, nonlinear
      additive effects were observed with combinations of genotypes at the LPL and
      apoAI-CIII loci, with the HDL-C and apoAI raising effect associated with the A75
      allele and H- allele seen only in those men with both alleles, and the apoCIII
      raising effect associated with the H+ and T alleles seen only in those with both
      alleles. Thus, variations at both of the LPL and apoAI-apoCIII loci influence
      levels of triglycerides, apoCIII, HDL-C, and apoAI, but these effects are
      strongly modulated by smoking and are different between men and women. The
      mechanisms for these interactions between smoking or gender and genes are
      unknown, but future studies should take such interactions into account.

PMID- 9181357
TI  - Genetics of type III hyperlipoproteinemia.
AB  - One hundred forty-seven relatives of 43 patients with "classical" type III
      hyperlipoproteinemia (HLP) having the apolipoprotein (apo) E2/2 phenotype were
      studied to determine the occurrence of hyperlipidemia and the presence of further
      possible genes for lipoprotein disorders in these families. In 12 pedigrees
      primary dyslipidemia was prevalent among patients and respective blood-relatives.
      In these kindreds the coexistent presence of genes for familial combined
      hyperlipidemia (n = 6), familial hypertriglyceridemia (n = 5), and familial
      hypercholesterolemia (n = 1), respectively, was supposed. Our results, therefore,
      confirm and extend previous data on the multifactorial genesis of the diseases.
      Besides homozygosity for a receptor binding-defective isoform of apo E (apo E2),
      additional genes for familial lipoprotein disorders might operate in the
      pathogenesis of type III HLP. This is the largest family study performed so far
      in this primary lipoprotein disorder.

PMID- 9181358
TI  - No association between the very low density lipoprotein receptor gene and late
      onset Alzheimer's disease nor interaction with the apolipoprotein E gene in
      population-based and clinic samples.
AB  - It is now commonly known that possession of one of the three common alleles of
      the apolipoprotein E (APOE) gene (allele epsilon 4) confers an increased risk for
      both familial and sporadic Alzheimer's disease (AD), and that this risk is dose
      dependent. Other genes that may play a role in AD, either through independent
      association with the disease or through modification of the existing APOE risk,
      are under investigation. One such gene, the very low density lipoprotein receptor
      (VLDL-R) gene, was reported by Okuizumi et al. to be independently associated
      with AD in a Japanese population, but not interactive with the APOE4 conferred
      risk. Their clinic-based data set demonstrated a 2-fold increased risk conferred
      by the 5-repeat allele of a polymorphism in VLDL-R. As recruitment from a clinic
      rather than a population-based sample may result in a distortion of allele
      frequencies, as has been shown with APOE allele frequencies, it is important to
      investigate this association in a population-based study. We have genotyped both
      population and clinic-based AD data sets at this VLDL-R polymorphism, and we find
      no independent association between the VLDL-R gene and the occurrence of AD in
      either sample. Further, despite the biochemical relationship between the VLDL-R
      and APOE proteins, we find no significant statistical interaction between the
      alleles at these loci.

PMID- 9181359
TI  - No association or linkage between an intronic polymorphism of presenilin-1 and
      sporadic or late-onset familial Alzheimer disease.
AB  - Recent reports have shown an association between an intronic polymorphism of the
      presenilin-1 (PSEN1) gene and late-onset (age at onset > 65) familial and
      sporadic (no family history) Alzheimer disease (AD). The reported association was
      independent of the effect of the only previously identified gene associated with
      late-onset AD, APOE. Blood samples were obtained from members of 122 multiplex AD
      families, 42 unrelated cases of AD with positive family histories of dementia,
      456 sporadic cases of AD, and 317 controls of similar ages at examination to the
      cases. These samples were genotyped for an intronic polymorphism of the PSEN1
      gene, located 3' to exon 8, and the data analyzed for evidence of association or
      linkage. The samples were also genotyped for APOE and the data analyzed to see if
      the association or linkage changed when controlling for APOE genotype. There was
      no statistically significant increase (at alpha = .01) in allele 1 (199 bp) or
      genotype 1/1 in the sporadic AD cases, or in a random sample of one affected from
      each multiplex family, compared to controls. When examining the effect of the
      PSEN1 polymorphism while controlling for APOE genotype, APOE genotype was
      strongly associated with AD, but the PSEN1 polymorphism genotype was not. Model
      trait dependent (lod score) and independent (Sim1BD) methods detected no evidence
      of linkage between PSEN1 and AD. In this independent dataset, the previously
      reported association between the intronic PSEN1 polymorphism and AD cannot be
      confirmed, and the conclusion that PSEN1 is a major susceptibility gene for late
      onset AD is not supported.

PMID- 9181360
TI  - Regressive logistic modeling of familial aggregation for asthma in 7,394
      population-based nuclear families.
AB  - The aim of this population-based study was to determine whether asthma aggregates
      in families, and if so, whether aggregation was consistent with environmental
      and/or genetic etiologies. Data were from 7,394 nuclear families (41,506
      individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian
      schoolchildren born in 1961 were surveyed by respiratory questionnaire completed
      by their parents. Similar data were obtained for parents and siblings of
      probands. For a child, having ever had asthma was predicted by a parent or
      sibling having ever had asthma; odds ratio (OR) = 3.13 (95% confidence interval
      [CI] 2.82-3.48) for mother, 2.99 (2.69-3.32) for father, and 3.47 (3.23-3.72) for
      a sibling. Regressive logistic modeling showed that, in addition to parent
      offspring effects, the data were consistent with the existence of an unmeasured
      factor shared by siblings, evident in 15% (SE 2%) of families and associated with
      a conditional OR of 9.68 (8.27-11.32). Familial aggregation was best described by
      a general oligogenic model with non-Mendelian transmission probabilities. Of the
      Mendelian models, a codominant model with an allele frequency of 16% (SE 0.3%)
      was preferred. Under a dominant model there was evidence for additional parent
      offspring and sibling effects of similar magnitude. It is unlikely that there is
      one major loci influencing asthma susceptibility; the overall effects of asthma
      genes in the population are more likely to be inherited codominantly, at least
      for the majority of loci of major etiological importance. The role of
      environmental factors in explaining part of familial aggregation for asthma
      cannot be ruled out, as major triggers of asthma attacks are familial.

PMID- 9181361
TI  - Pathology of malignant mesothelioma.
AB  - The diagnosis of malignant mesothelioma can pose several problems to the surgical
      pathologist. First, the morphological appearances of the tumour are known to be
      diverse with mimicry of a range of both reactive and neoplastic conditions.
      Second, due to the relative inaccessibility of the serosa, biopsy material is
      often scanty and fragmentary, producing a plethora of interpretive ambiguities.
      Third, adjunct techniques such as mucin histochemistry and immunohistochemistry,
      whilst useful in excluding malignant mesothelioma have little role in confirming
      the diagnosis. The accurate diagnosis of diffuse malignant mesothelioma is
      important for two reasons: (1) In relation to prognosis as it has an almost
      invariable fatal outcome, which contrasts with the other mesothelial neoplasms
      such as the benign adenomatoid tumour and the borderline malignant tumours,
      namely the well-differentiated papillary mesothelioma and multicystic
      mesothelioma; (2) In relation to occupational-related compensation claims
      following asbestos exposure. This review summarizes the aetiology of asbestos
      induced neoplasia, possible mechanisms of tumour development and highlights
      potential diagnostic pitfalls.

PMID- 9181362
TI  - Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating
      malignant pleural mesothelioma.
AB  - We report two cases of autopsy confirmed angiosarcoma in adult males, presenting
      as diffuse pleuropulmonary tumours and simulating malignant mesothelioma. Both
      the lesions grew along the serosal surfaces and were characterized by variably
      thick rinds of tissue encasing the lung. The pulmonary parenchyma showed diffuse,
      dark red, subpleural consolidations and multiple cavitations. Histologically, the
      lesions were composed by atypical spindle and polygonal, epithelioid cells
      showing rudimentary vascular differentiation and exhibiting strong positivity for
      factor VIII, CD31, CD34 and vimentin, We conclude that angiosarcoma may present
      with preponderant or exclusive involvement of pleura and peripheral lung and that
      it should be added to the list of tumours capable of simulating malignant
      mesothelioma.

PMID- 9181363
TI  - Genetic evidence for a clonal link between low and high-grade components in
      gastric MALT B-cell lymphoma.
AB  - High-grade MALT lymphomas often contain low-grade tumour components; both cell
      populations have been shown to express the same immunoglobulin light chain
      previously. However, the clonal link between the low and high-grade components
      has not been established at the genetic level. To investigate this link, we have
      examined low- and high-grade components micro-dissected from tissue sections of
      four high-grade gastric MALT lymphomas. PCR and sequence analyses were performed
      to identify clone-specific rearranged immunoglobulin heavy chain gene sequences.
      In each of these cases, the PCR products from the two components were identical
      in size by electrophoresis. Direct sequencing revealed common clone-specific
      immunoglobulin heavy chain gene rearrangements in both lesions of each case,
      providing genetic evidence for a clonal link. These results support the proposal
      that high-grade MALT lymphomas generally evolve from low-grade clones.

PMID- 9181364
TI  - Pathogenetic role of the stromal cells in endometriosis and adenomyosis.
AB  - Ten cases of endometriosis of bowel, ovaries, uterine serosa and 10 cases of
      adenomyosis were studied. Blocks of tissue with areas of interest were submitted
      for serial sectioning of the entire block. Some sections were immunostained for
      oestrogen receptor, vimentin, Ber-EP-4 and cytokeratins. The common finding was
      the presence of type 1 nodules, consisting of isolated nodules of endometrial
      stromal cells without endometrial glands, along blood or lymphatic vessels. The
      stromal cells showed positive immunoreactivities for oestrogen receptor and
      vimentin, and negative reactivities for cytokeratins. Due to the absence of
      connection with adjacent endometriosis or adenomyosis, it is likely that these
      endometrial stromal nodules arise from the multipotential pericytes. In addition,
      in serosa of all cases of endometriosis, type 2 nodules, having adjacent
      mesothelium (Ber-EP4-) changing into epithelium (Ber-EP4+) and type 3 nodules,
      with non-endometrial epithelium (oestrogen receptor-) changing into endometrial
      gland (oestrogen receptor+) were identified. We believe that the formation of
      type 1 nodules from the pericytes and the transformation of the mesothelium into
      endometrial glands in type 2 and 3 nodules are accomplished through the process
      of induction by the endometrial stroma, and the proliferation is controlled by
      genetic, hormonal and immunological factors. Type 1, 2 and 3 nodules are likely
      to represent a histological continuum in the development of early endometriosis.
      Subsequent to the formation of endometriosis in the serosa, the pathway of
      development of endometriosis and adenomyosis is similar. Through the processes of
      induction and proliferation there is an increase in size of the stroma of type 1
      nodules and that of endometrial tissue with subsequent fusion of the stroma of
      type 1 nodules and that of foci of adenomyosis or endometriosis. Consequently,
      there is enlargement of the stroma of the foci of adenomyosis or endometriosis.
      The 'newly enlarged stroma' serves as 'new soil' for further growth of the
      endometrial glands in the endometrial tissue.

PMID- 9181365
TI  - Keratin expression in anal carcinoma: an immunohistochemical study.
AB  - The keratin expression of 40 frozen tissue specimens of anal carcinoma was
      investigated using a panel of 17 monoclonal antibodies to 14 individual keratins.
      The tumours were divided into three histological subgroups showing pure squamous,
      squamous and basaloid, or squamous and glandular differentiation. A further
      assessment of the tumour grade was made. The overall profile was of expression of
      keratins 4, 13, 17, 18 and 19 across the majority of the tumours, with the
      minority expressing keratins 1 and 10, and keratin 7. Dedifferentiation was
      associated with loss of expression of keratinocyte keratins, particularly the
      cornification markers keratin 1 and 10, and K6 and 16 associated with
      keratinocyte hyperproliferation and differentiation. This correlated with
      acquisition of the simple epithelial keratins 7 and 8. Compared with the tumours
      as a whole, well differentiated squamous tumours (the most easily identifiable
      histological group) showed consistent positivity for keratins 6 and 16, expressed
      suprabasally, while simple keratins 18 and 19 were also found. Independent of
      grade, mixed tumours showed more widespread positivity for simple epithelial
      keratins 7, 8 and 18 and loss of expression of cornification keratins 1 and 10
      and K6 and 16 compared with pure squamous tumours. The relatively limited keratin
      profile of pure squamous tumours, predominantly consisting of keratinocyte
      keratins, suggests that these malignancies are less likely to originate from the
      region of the anal canal where the keratin profile is heterogeneous, i.e. the
      anal transitional zone.

PMID- 9181366
TI  - Solitary fibrous tumour of the renal peripelvis.
AB  - Solitary fibrous tumours (SFTs) are rare spindle cell neoplasms generally
      associated with the serosal surface, especially the pleura. This report describes
      two SFTs arising in the renal peripelvis, occurring in 33- and 36-year-old
      females. The lesions lacked the characteristic features of other recognized
      neoplasms that occur in the kidney. Immunohistochemically, the tumour cells were
      diffusely and strongly positive for vimentin and CD34, and some tumour cells
      expressed alpha-smooth muscle actin. Both tumours were diploid by flow cytometry.
      Both patients have had benign clinical courses with 7.5- and 1-year follow-up.
      The findings suggest that the SFTs may originate from peripelvic mesenchymal
      cells, a new location for SFT. SFT should be included in the differential
      diagnosis of spindle cell tumours arising in the renal pelvis and peripelvis.

PMID- 9181367
TI  - Dedifferentiated myxoid liposarcoma: a clinicopathological study suggesting a
      closer relationship between myxoid and well-differentiated liposarcoma.
AB  - Myxoid/round cell liposarcoma is arguably the commonest type of liposarcoma
      occurring in the extremities and may show gradual progression from low-grade,
      pure myxoid liposarcoma to high-grade round cell liposarcoma. Rarely myxoid/round
      cell liposarcoma is associated with areas of well-differentiated or pleomorphic
      liposarcoma (mixed liposarcoma). We describe the clinicopathological features of
      three unusual myxoid/round cell liposarcomas which showed morphological features
      of de novo dedifferentiation. All patients were male and were aged 66, 70 and 76
      years, respectively. One lesion each arose in the retroperitoneum, inguinal
      region and peritoneal cavity. Histologically, in one case the myxoid/round cell
      component was juxtaposed to a high-grade non-lipogenic component resembling non
      pleomorphic storiform 'malignant fibrous histiocytoma' ('MFH'), one case showed a
      combination of myxoid liposarcoma and a high-grade myxofibrosarcoma-like
      component (so-called myxoid 'MFH'), and in the third case, a well-differentiated
      myxoid liposarcoma with a discontinuous micronodular pattern of dedifferentiation
      was seen. Follow-up information of 30, 28 and 26 months revealed two recurrences
      each in two patients. These patients died of postoperative pulmonary embolism and
      abdominal haemorrhage, respectively; systemic metastases were not noted. These
      cases demonstrate that myxoid/round cell liposarcoma can show, albeit very
      rarely, histological features of dedifferentiation. Cases like these, combined
      with the occurrence of mixed-type liposarcoma (well-differentiated/myxoid
      liposarcoma) and the vicinity of chromosomal regions involved by specific
      karyotypic aberrations in these tumours, suggest that myxoid/round cell
      liposarcoma and well-differentiated liposarcoma (including its dedifferentiated
      variant) are more closely related in biological terms than is generally believed.

PMID- 9181368
TI  - Morphological and immunohistochemical characterization of granular cells in non
      hypophyseal tumours of the central nervous system.
AB  - We report 14 biopsy cases of granular cell tumours (GCT) of the central nervous
      system (CNS) outside the pituitary gland. In six cases the granular cells
      determined the morphology (actual GCT), the other eight consisted of different
      CNS tumours with a varying granular cell component. Pronounced immunoreactivity
      for ubiquitin and alpha-1-antichymotrypsin could be found in all investigated
      tumours, while GFAP, neuron specific enolase, von Willebrand factor, vimentin, S
      100 protein, alpha-1-antitrypsin, actin, and the neurofilaments 68 kDa and 160
      kDa showed mostly weak positivity in some cases. Four out of eight GCT showed no
      immunoreactivity for MIB1; the other four cases had a proliferation index between
      0.5% and 15%. Six out of nine cases were positive for p53. We consider granular
      cells to originate from different cell types. Thus, although morphologically
      identical, GCT are actually biologically heterogeneous. GCT of the CNS may
      represent gliomas of mostly astrocytic origin with a metabolically induced
      transformation of some tumour cells into granular cells.

PMID- 9181369
TI  - Histopathology and microbiology of isolated rectal bleeding in neonates: the so
      called 'ecchymotic colitis'.
AB  - Rectal bleeding in neonates is an alarming event which suggests a possible
      necrotizing enterocolitis (NEC) but is usually the only symptom of an unexplained
      colitis characterized endoscopically by ecchymotic mucosal lesions, the so-called
      'ecchymotic colitis' (EC). We studied histologically and bacteriologically 18
      infants (mean age: 18 days) presenting with rectal bleeding by systematic
      rectosigmoidoscopy and intestinal biopsies. The 18 infants were hospitalized.
      Prematurity was found in seven cases and an underlying condition in 14 cases
      (respiratory distress: six cases; infection: six cases; surgery: two cases).
      Histology showed a mild to moderate inflammation (10/12) of the mucosa with a
      prevalence of polymorphonuclear cells (8/10), frequent focal haemorrhages (11/12)
      and foci of pneumatosis (4/12). Numerous bacteria were seen in the mucus layer
      focally forming large clusters. Cultures of intestinal biopsies yielded
      exclusively Enterobacteriaceae species: Escherichia coli (seven cases),
      Klebsiella spp. (seven cases), and Enterobacter cloacae (three cases); four cases
      were sterile. Our study demonstrates that neonatal bleeding is associated with
      endoscopic and histological 'ecchymotic colitis' lesions and with a peculiar
      microbial flora of EBC strains. EC and necrotizing enterocolitis share similar
      features raising the question of the link between the two syndromes.

PMID- 9181370
TI  - Nuclear pleomorphism in typical carcinoid tumours of the lung: problems in frozen
      section interpretation.
AB  - Pulmonary typical carcinoid tumours are generally easy to diagnose with their
      uniform cells, carcinoid growth pattern and lack of mitoses. However, nuclear
      pleomorphism, which is common in other neuroendocrine tumours, is not emphasized
      in pulmonary carcinoid tumours. Three cases of typical carcinoid tumours, because
      of marked nuclear pleomorphism on frozen section, were misdiagnosed as non-small
      cell carcinomas.

PMID- 9181371
TI  - Regulary organized lymphoid tissue and CD40 ligand expression in a male fetus
      carrying the defective gene for X-linked lymphoproliferative disease (XLP).

PMID- 9181372
TI  - Primitive neuroectodermal tumour of the uterus with focal cartilaginous
      differentiation.

PMID- 9181373
TI  - Primary peripheral primitive neuroectodermal tumour of urinary bladder.

PMID- 9181374
TI  - Mucinous cholangiocarcinoma: an unusual complication of hepatolithiasis and
      recurrent pyogenic cholangitis.

PMID- 9181375
TI  - Dermatofibroma with granular cells.

PMID- 9181376
TI  - Melanosis of the oesophagus in a Western patient.

PMID- 9181377
TI  - Procalcitonin, a marker of bacterial infection.

PMID- 9181378
TI  - Nosocomial infections by Listeria monocytogenes: analysis of a cluster of
      septicemias in immunocompromised patients.
AB  - From December 1994 to November 1995 an unusual accumulation of Listeria
      infections occurred at the University Hospital Hamburg-Eppendorf, Germany. Eleven
      immunosuppressed patients from different departments developed septicemia due to
      Listeria monocytogenes during hospitalization. In a retrospective study,
      serotyping and pulsed-field gel electrophoresis revealed that six isolates were
      identical or genetically related. Four of them had been isolated from renal
      transplant recipients. Listeria monocytogenes was neither detected in food
      samples of the renal transplantation ward, nor in stool specimens obtained from
      the ward staff. There had been no close contacts among the infected patients.
      Before transplantation, the renal transplant recipients had been dialysed in
      different dialysis centers. Nosocomial foodborne transmission could not be proven
      but seems likely.

PMID- 9181381
TI  - A seroepidemiologic survey on brucellosis antibodies in southern Italy.
AB  - This study investigated the prevalence of Brucella antibodies in the general
      population in two regions in southern Italy. A total of 1,294 subjects were
      recruited from January to June 1996 among patients attending randomly selected
      public and private laboratories and pediatric outpatient clinics. Information on
      sex, age, residence, and occupation was recorded. Seroprevalence of brucellosis
      was studied by the safranin O-stained antigen microagglutination test. The chi
      square test and multiple logistic regression were performed. An overall
      prevalence of brucellosis of 3.1% was recorded; no significant difference was
      found between the two regions, with values of 2.7% in Campania and 3.8% in
      Calabria. Multiple logistic regression analysis indicated that positivity to
      brucellosis was significantly associated with the province the subjects reside
      in, ranging from 0 in Salerno to 6.2% in Caserta, and that it significantly
      increased with age, ranging from 1% in persons under 16 to 4.2% in those over 65
      (OR = 1.7; 95% CI = 1.04-2.6), whereas it was not significantly associated with
      sex. When analysis was conducted after restriction to subjects reporting to be
      working, occupation was found not to be significantly associated with
      brucellosis. Since the spread of the disease is still of concern, though
      circulation of Brucella is decreasing, strict application of measures for the
      eradication of brucellosis from livestock, pasteurization of milk and dairy
      products, and education regarding eating habits must be pursued.

PMID- 9181379
TI  - Lyme borreliosis--an overdiagnosed disease?
AB  - Ninety-nine patients who were referred to a clinic for infectious diseases on
      suspicion of Lyme borreliosis and whose major symptoms were fatigue, headache,
      myalgia and arthralgia were studied retrospectively to find out if there was any
      difference in symptomatology between patients who were seropositive or
      seronegative to Borrelia burgdorferi. 64/82 (78%) patients remembered one or more
      tick bites during previous years and 32/74 (43%) patients had a history of
      erythema migrans. Fatigue, headache, myalgia and arthralgia occurred in 84%, 72%,
      54%, and 63% of the patients, respectively. 62/99 (63%) patients had an elevated
      IgM and/or IgG antibody titer to B. burgdorferi. There was no difference in
      frequency of symptoms between seropositive and seronegative individuals. 48/99
      (49%) patients were treated with antibiotics, mostly oral doxycycline. Only 50%
      were improved after treatment. On follow-up 2 to 4 years after the first visit,
      40% of the patients had recovered completely, 31% were improved, 24% reported
      unaltered symptoms and four patients were impaired. There was no difference in
      symptoms on follow-up between seropositive or seronegative patients. It is
      concluded that there probably is an overdiagnosis of Lyme borreliosis and that
      better microbiological methods are needed to confirm active disease.

PMID- 9181380
TI  - Cytomegalovirus infection in newborns and their family members: polymerase chain
      reaction analysis of isolates.
AB  - Polymerase chain reaction (PCR) analysis with primers for the pp65, a-sequence,
      glycoprotein B, and major immediate early genes of human cytomegalovirus (CMV)
      was used to study five congenitally-infected infants and their CMV-infected
      family members. Family members excreting CMV included three mothers and two
      siblings. The PCR results indicated that the CMV strain excreted by each infant
      was indistinguishable from that excreted by the corresponding family member. By
      contrast, the molecular profiles of the CMV strains were distinct between
      families, indicating that the PCR algorithm described in this study is a useful
      method for analyzing CMV strains.

PMID- 9181382
TI  - Comparative effects of cefadroxil and phenoxymethylpenicillin on the normal
      oropharyngeal and intestinal microflora.
AB  - The ecological effects on the commensal microflora in saliva and stool samples
      were studied during administration of two commonly used antibiotics: cefadroxil
      500 mg b.i.d. for 10 days and phenoxymethylpenicillin 1 g b.i.d. for 10 days.
      Twenty healthy volunteers participated in the study. In the oropharyngeal
      microflora the aerobic microflora was significantly suppressed during
      administration of cefadroxil while no significant changes were noticed in the
      anaerobic microflora. Administration of phenoxymethylpenicillin caused a strong
      decrease in the number of viridans streptococci and an overgrowth of Neisseria
      cocci. The total numbers of anaerobic oropharyngeal microorganisms were
      suppressed during phenoxymethylpenicillin administration. In the intestinal
      microflora the variation in numbers of aerobic and anaerobic microorganisms was
      minor in both groups. The microflora became normalised 2 weeks after withdrawal
      of the drugs. It was concluded that peroral administration of cefadroxil to
      healthy volunteers resulted in minor ecological disturbances in the oropharyngeal
      and intestinal microflora, which were in the same range as for
      phenoxymethylpenicillin.

PMID- 9181383
TI  - Campylobacter jejuni gastroenteritis in Turkish children.
AB  - Four hundred children between the ages of 1 month and 14 years with the complaint
      of diarrhea were studied to assess Campylobacter jejuni isolation rates in
      childhood acute gastroenteritis in Turkey and to clarify clinical presentations
      of C. jejuni enteritis. C. jejuni was found to be the second most common isolate
      with a rate of 8.3%, the first being Shigella strains. The highest isolation rate
      was in the 6 to 14-year age range at 12%. The most frequent symptoms in patients
      with C. jejuni enteritis were abdominal pain (51.5%), vomiting (36.4%) and fever
      (30.3%). Stool examination revealed bloody mucous stool in 51.5% of the patients,
      and erythrocytes and/or leucocytes were detected in 42.4%. Only 12.1% of the
      patients with C. jejuni enteritis were hospitalized in this study.

PMID- 9181385
TI  - Cyclospora cayetanensis: first imported infections in Germany.
AB  - Over the last decade increasing numbers of enteritis cases have been attributed
      to infection with a new coccidian species that was named Cyclospora cayetanensis
      in 1993. Diarrhea caused by this agent is clinically indistinguishable from
      cryptosporidiosis, isosporiasis and microsporidiosis, but Cyclospora infections
      are often very prolonged (up to 15 weeks) and may cause severe weight loss.
      Diagnosis of infection is important because, in contrast to diarrhea caused by
      Cryptosporidium and microsporidia, treatment with co-trimoxazole is effective.
      Here we report the cases of two female patients, aged 70 and 58 years old,
      respectively, who suffered from severe, prolonged diarrhea after a vacation in
      Singapore, Java and Bali. Routine microbiological laboratory diagnostics were
      unable to demonstrate the presence of known enteropathogenic bacteria. Modified
      Ziehl-Neelsen staining of fecal smears revealed oocysts of Cyclospora
      cayetanensis, and treatment of the patients with co-trimoxazole was promptly
      effective. We would like to increase awareness of the possibility of Cyclospora
      infections in patients with prolonged diarrhea who have travelled to endemic
      areas.

PMID- 9181384
TI  - Efficacy of twice-daily dosing of amoxycillin/clavulanate in acute otitis media
      in children.
AB  - Children with acute otitis media (AOM), aged 2-12 years, were randomised to 10
      days treatment with amoxycillin/clavulanate (A/C) 70/10 mg/kg/day given b.i.d.
      (231 patients) or to A/C 60/15 mg/kg/day given t.i.d. (232 patients). Clinical
      success rates at end of therapy (10-17 days) were 91.8% for the b.i.d. group and
      90.5% for the t.i.d. group and at follow-up (28-42 days) were 80.1% for the
      b.i.d. group and 77.6% for the t.i.d. group, indicating that the b.i.d. regimen
      was as effective as the t.i.d. regimen. There was no statistically significant
      difference in incidence of adverse experiences between the two groups. The
      overall incidence of protocol defined diarrhoea assessed from diary booklets was
      low, with a lower incidence in the b.i.d. group (6.7%) than in the t.i.d. group
      (10.3%). Significantly more patients in the b.i.d. group (83.1%) than in the
      t.i.d. group (72.8%) had at least 80% compliance over a 7-10 day treatment
      period. A/C given twice or three-times daily was highly effective in the
      treatment of AOM in children. The two regimens showed equivalent clinical
      efficacy, both were well tolerated, and there was evidence of improved compliance
      with the b.i.d. regimen.

PMID- 9181386
TI  - Central nervous system infection due to Clostridium septicum: a case report and
      review of the literature.
AB  - A patient with end stage breast cancer was admitted to hospital due to fever,
      chills, multiply eroded discharging wounds, and sudden onset of left hemiparesis.
      Clostridium septicum bacteremia and brain abscess were diagnosed. The patient was
      treated successfully with intravenous penicillin and clindamycin and stereotactic
      aspiration of the abscess. Eleven cases of C. septicum central nervous system
      infection are reviewed. They showed an extremely fulminant course and high
      fatality. Nevertheless, some relationship seems to exist between outcome and type
      of brain lesion. Hemolytic-uremic syndrome associated with central nervous system
      infection is also discussed, because all these cases in the literature were due
      to this organism. Early diagnosis and aggressive treatment, including surgical
      drainage and appropriate antibiotics, are the key to improving the prognosis. A
      long-term prophylactic oral antimicrobial agent is suggested for patients who
      survive this infection.

PMID- 9181387
TI  - Interpretive criteria for susceptibility testing of coagulase-negative
      staphylococci with special reference to netilmicin.
AB  - Antibiotic susceptibility of 171 isolates of coagulase-negative staphylococci
      from 66 preterm infants at a neonatal intensive care unit was tested by the
      microbroth dilution method. Results were interpreted according to DIN as well as
      according to NCCLS. Because of the bimodal distribution of MIC values within the
      CNS population tested, results of susceptibility interpretation according to DIN
      were identical to NCCLS with the exception of netilmicin (NCCLS: 89%
      susceptibility; DIN: 16% susceptibility). Since netilmicin is frequently used for
      treatment of infections caused by coagulase-negative staphylococci, this
      difference may be of clinical significance.

PMID- 9181388
TI  - Tissue penetration of sparfloxacin in a rat model of experimental Escherichia
      coli epididymitis.
AB  - The epididymal, testicular, and prostatic tissue penetration of sparfloxacin, a
      new quinolone, was assessed in a rat model of acute epididymitis. Seventy-two
      hours after injection of 0.1 ml (10(6) cfu/ml) of an Escherichia coli suspension
      into the right epididymis via the right ductus deferens, a single oral dose of
      sparfloxacin 50 mg/kg body weight was administered. One, 2, 4, 8, 12, and 24 h
      after administration the animals were sacrificed and the sparfloxacin
      concentrations and "areas under the curve" (AUC0-24) in both epididymides, both
      testes, the prostate gland and in the serum were measured by bioassay. The
      highest mean AUC0-24 was found in the prostate gland, followed by left
      epididymis, right epididymis, serum, right testis, and left testis (190, 79, 60,
      28, 12, and 9 mg/kg x h, respectively). Though there was no statistically
      significant difference in the sparfloxacin concentration of both epididymides (p
      = 0.09), the mean AUC0-24 was significantly higher in the non-infected left
      epididymis (p < 0.0001). The AUC0-24 and sparfloxacin concentrations of the right
      infected epididymis were significantly higher than those observed in the serum (p
      < 0.0001). In both testes, the AUC0-24 and sparfloxacin concentrations were lower
      than in the serum (p < 0.0001), however, the concentration exceeded the MIC
      tenfold for approximately 20 h. It is concluded that the pharmacokinetic
      properties of sparfloxacin (good in vitro activity, high penetration into the
      prostate gland, testes, infected and non-infected epididymides) make this drug a
      recommendable choice for the initial treatment of acute epididymitis caused by E.
      coli.

PMID- 9181389
TI  - Postpartal endomyometritis in a case of unknown tertian malaria.
AB  - A 28-year-old woman developed puerperal endomyometritis and tertian malaria
      simultaneously. She delivered her child by vacuum extraction during week 41 of
      pregnancy in September 1994. The peripartal period was uneventful. Nine days post
      partum the patient was readmitted to hospital with fever and pain in the area of
      the episiotomy. On day 13 post partum a hysterectomy was performed because of
      suspected abscess-forming endomyometritis. Two days after the hysterectomy the
      patient developed septic temperatures, which persisted for 10 days. Tertian
      malaria due to Plasmodium vivax was found to be the cause of fever. The patient
      had been in Indonesia without anti-malarial prophylaxis in 1991. Two years later
      she travelled to Ghana, having taken mefloquine as prophylaxis. Malaria was
      obviously caused by reactivated hypnozoites in the liver, although the patient
      had never had an episode of fever associated with malaria before. This case
      proves that tertian malaria may "recur" even without previous manifestation,
      years after a stay in a region endemic for malaria.

PMID- 9181390
TI  - Defective reactive oxygen metabolite generation by macrophages from acute
      brucellosis patients.

PMID- 9181391
TI  - Antibiotic-associated diarrhea in HIV-infected patients receiving clindamycin.

PMID- 9181392
TI  - It is futile to use interferon in HCV-related chronic hepatitis with viremia
      levels above 3 x 10(6) eq/ml.

PMID- 9181393
TI  - Fluconazole concentrations in pulmonary tissue and pericardial fluid.
AB  - In order to investigate the clinical efficacy of the triazole antifungal agent
      fluconazole (FCA) in the treatment of pulmonary mycosis, in the present study the
      concentrations of fluconazole in human pulmonary tissue, pericardial fluid and
      serum were determined at 1, 2, 12 and 13 h after intravenous administration of
      fluconazole 200 mg. The mean FCA concentrations in the serum were 4.04 mg/l (1
      h), 3.82 mg/l (2 h), 2.35 mg/l (12 h) and 2.13 mg/l (13 h). The respective FCA
      levels in the pulmonary tissue were 4.64 mg/kg, 4.54 mg/kg; 3.50 mg/kg and 3.40
      mg/kg and the concentrations in the pericardial fluid were 3.86 mg/l, 3.57 mg/l,
      2.35 mg/l and 2.13 mg/l. The FCA concentrations in the pulmonary tissue that were
      statistically significant higher than the serum concentrations were found at 2 h,
      12 h and 13 h after intravenous administration (p < 0.05).

PMID- 9181394
TI  - Healthcare workers: protecting those who protect our health.

PMID- 9181395
TI  - A survey of policies at children's hospitals regarding immunity of healthcare
      workers: are physicians protected?
AB  - OBJECTIVE: To determine policies at children's hospitals regarding immunizations,
      annual tuberculosis (TB) screening, and blood or body fluid exposure follow-up,
      particularly as they apply to physicians. DESIGN AND PARTICIPANTS: A three-page
      survey was sent to infection control practitioners (ICPs) in April 1994 at
      hospitals affiliated with the National Association of Children's Hospitals and
      Related Institutions. One follow-up mailing was sent to nonresponding ICPs.
      RESULTS: Responses were received from 62 (67%) of 93 ICPs. Thirty-five (66%) of
      53 children's hospitals had an immunity policy that applied to medical students,
      42 (79%) of 53 to resident physicians, 32 (52%) of 62 to hospital-based
      physicians, and 18 (29%) of 62 to private or community physicians (who admit
      patients to one hospital). Physicians were required to show evidence of an annual
      TB screen at 36 hospitals (58%). Immunity policies or TB screening were provided
      for the following physician groups: medical students, 13 (21%); resident
      physicians, 43 (69%); hospital-based physicians, 50 (81%); and private or
      community physicians, 23 (37%). Infection control practitioners reported that the
      following diseases had been identified within the past 5 years at their
      hospitals: measles, 82%; mumps, 40%; rubella, 31%; TB, 94%; hepatitis B, 94%;
      pertussis, 90%; varicella, 98%; and influenza, 94%. Physicians in these
      institutions were reported to have contracted the following diseases from patient
      exposure: measles, hepatitis B, TB, pertussis, varicella, and influenza.
      CONCLUSION: Children's hospitals vary widely in their policies regarding
      healthcare-worker immunity, and, in many cases, physicians may not be protected
      from nosocomial transmission of community infections.

PMID- 9181396
TI  - Varicella vaccination for healthcare workers at a university hospital: an
      analysis of costs and benefits.
AB  - OBJECTIVE: To demonstrate the costs and benefits of vaccinating varicella
      susceptible healthcare workers at a university hospital with live, attenuated
      varicella-zoster virus vaccine. DESIGN: Retrospective review of employee medical
      records and data on the cost of special paid absence for susceptible healthcare
      workers after exposure to varicella or herpes zoster. SETTING: A 988-bed tertiary
      care university hospital. RESULTS: In 1994, 224 hospital employees (3.4%) were
      susceptible to the varicella-zoster virus. There were 40 exposures to varicella
      and herpes zoster in that year, involving 29 of the susceptible employees. Nine
      (31%) of the exposed susceptibles became varicella immune by indirect fluorescent
      antibody testing subsequent to exposure. Seventeen (59%) have had multiple
      varicella exposures and special paid absences while employed by the hospital. In
      1994, wages paid to healthcare workers while furloughed for the communicable
      period following varicella exposure totaled $38,463.93. An additional $24,748.74
      was paid to replacement workers during that same time. Varicella vaccine to
      immunize all 224 susceptibles in 1994 would have cost $17,920. Absences due to
      varicella and herpes zoster exposure also result in disruptions to patient care.
      CONCLUSIONS: Varicella vaccination for varicella-susceptible healthcare workers
      at a university hospital would result in financial savings and improved patient
      care. We recommend that other institutions consider the costs and benefits of
      adopting a varicella immunization program for their susceptible employees.

PMID- 9181397
TI  - Nosocomial respiratory syncytial virus infections: prevention and control in bone
      marrow transplant patients.
AB  - OBJECTIVE: To assess the effectiveness of a multifaceted infection control
      strategy in limiting the nosocomial transmission of respiratory syncytial virus
      (RSV) infection to patients in a bone marrow transplant (BMT) unit. DESIGN:
      Before/after trial. SETTING: University-affiliated tertiary cancer center.
      PATIENTS: Adult BMT recipients hospitalized during two consecutive wintertime
      community outbreaks of RSV infection. INTERVENTIONS: An infection control
      strategy against nosocomial RSV infection was implemented in the BMT unit in
      February 1993. The strategy involved prompt identification, isolation, and
      cohorting of RSV-infected patients; prompt therapy with aerosolized ribavirin;
      use of masks and gloves by anyone entering an infected BMT patient's room;
      screening visitors for respiratory symptoms; restricting visitation by all
      children under 12 years of age and all family members and other visitors with RSV
      symptoms; and restricting symptomatic hospital staff from working in the BMT
      unit. RESULTS: After implementation of the multifaceted infection-control
      strategy, there were four cases of nosocomial RSV infection in 3,870 patient days
      (incidence density, 1.0 case/1,000 patient days) compared with 14 cases of
      nosocomial RSV infection in 3,152 patient days (incidence density, 4.4
      cases/1,000 patient days) during the 1992-1993 RSV season (rate ratio, 4.4; 95%
      confidence interval [CI95]. 1.4-17.9: P < .01). This decrease in incidence
      occurred despite a comparable prevalence of community-acquired RSV cases between
      the two seasons (2.2% vs 3.2% in 1992-1993 and 1993-1994, respectively;
      prevalence ratio, 0.7; CI95, 0.2-2.1; P = 0.5). CONCLUSION: Institution of a
      multifaceted infection control strategy significantly reduced the frequency of
      nosocomial RSV infection in a high-risk group of adult BMT recipients.

PMID- 9181398
TI  - Susceptibility of antibiotic-susceptible and antibiotic-resistant hospital
      bacteria to disinfectants.
AB  - OBJECTIVE: To evaluate whether hospital strains of antibiotic-resistant bacteria
      exhibited altered susceptibility to disinfectants. DESIGN: Antibiotic-susceptible
      bacteria were obtained from American Type Culture Collection: Staphylococcus
      aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae,
      Salmonella choleraesuis, and Pseudomonas aeruginosa. Hospital strains of
      antibiotic-resistant bacteria were obtained from clinical isolates, including: S
      aureus, S epidermidis, E coli, Enterococcus species, K pneumoniae, and P
      aeruginosa. The Association of Official Analytical Chemist's use-dilution method
      was used to test these 12 strains of 7 bacterial pathogens for their
      susceptibility to a phenol and a quaternary ammonium compound. For five
      pathogens, we tested a susceptible and a more resistant strain in 20 comparative
      trials (5 pathogens, 2 disinfectants, 2 dilutions per disinfectant). RESULTS: In
      our 20 comparative trials, the antibiotic-resistant strains exhibited an
      increased resistance to the disinfectant in only a single instance. CONCLUSIONS:
      Our data demonstrate that the development of antibiotic resistance does not
      appear to be correlated to increased resistance to disinfectants.

PMID- 9181399
TI  - Nosocomial transmission of human immunodeficiency virus and subsequent
      transmission of multidrug-resistant tuberculosis in a healthcare worker.
AB  - A phlebotomist with nosocomially acquired human immunodeficiency virus infection
      developed tuberculosis 10 months after exposure to multidrug-resistant
      Mycobacterium tuberculosis during a nosocomial outbreak. Healthcare workers with
      immunosuppression are at increased risk of tuberculosis if infected and, if
      exposed, should be considered for preventive therapy regardless of tuberculin
      skin-test status.

PMID- 9181401
TI  - How to select and interpret molecular strain typing methods for epidemiological
      studies of bacterial infections: a review for healthcare epidemiologists.
      Molecular Typing Working Group of the Society for Healthcare Epidemiology of
      America.
AB  - Strain typing is an integral part of epidemiological investigations of nosocomial
      infections. Methods for distinguishing among bacterial strains have improved
      dramatically over the last 5 years, due mainly to the introduction of molecular
      technology. Although not all molecular techniques are equally effective for
      typing all organisms, pulsed-field gel electrophoresis is the technique currently
      favored for most nosocomial pathogens. Criteria to aid epidemiologists in
      interpreting results have been published. Nucleic acid amplification-based typing
      methods also are applicable to many organisms and can be completed within a
      single day, but interpretive criteria still are under debate. Strain typing
      cannot be used to replace a sound epidemiological investigation, but serves as a
      useful adjunct to such investigations.

PMID- 9181400
TI  - Evaluation of integrity of gloves used in a flow cytometry laboratory.
AB  - This study was conducted to evaluate the effect of normal use on latex glove
      integrity in a flow cytometry laboratory. The gloves were tested using the 1,000
      microL water-tight test and met industrial standards (less than 4% leakage)
      before, but not after use. More durable gloves, or more frequent changes of
      gloves, may be needed to ensure adequate barrier protection for laboratory
      workers during routine procedures.

PMID- 9181402
TI  - Microcomputers in hospital epidemiology.
AB  - Computers can store, manage, and analyze large quantities of data. Thus,
      computers are an ideal tool for the modern practice of infection control. This
      article provides practical information for infection control personnel who must
      choose or upgrade a computer system.

PMID- 9181404
TI  - A timely focus on nursing practice.

PMID- 9181405
TI  - Nursing care as a calling.
AB  - A calling is a deep desire to devote oneself to serving people according to the
      high values of the task or profession. The aim of this study is to clarify the
      relationship between a calling experience and professional knowledge, nursing
      action and motivation. The data were collected from all the registered nurses (n
      = 179) at five hospitals. The response was 70%. The nurses who were committed to
      their profession and experienced their job as a calling, had a good knowledge
      about the ill feeling and maladjustment of their patients and were also good
      sources of support for their patients. They understood the importance of family
      ties and offered support to their patients' families. They were aware of the
      needs of dying patients and their concern with spiritual questions, and satisfied
      these needs well. It was characteristic for them to collaborate closely within a
      team, to experience the content of their work as enriching and to possess
      proficient professional abilities. They were therefore excellent in supporting
      both the individual patient and his or her family. They had a deep understanding
      of the whole process of patient care. According to these results the calling
      experience is not in conflict with professional principles.

PMID- 9181403
TI  - The challenge of postoperative infections: does the surgeon make a difference?
AB  - Postoperative infections remain a challenge in many surgical procedures despite
      improved surgical technique and powerful antibiotics. The number of sepsis cases
      has tripled from 1979 to 1992 due to increased invasive procedures in older and
      immune-suppressed patients. Increasingly, in recent years, outbreaks of resistant
      pathogens have been published, provoking the question of how postoperative
      infections and resistant pathogens should be dealt with. Wound classification and
      risk stratification were developed to identify patients at risk for postoperative
      infection. However, other important intrinsic factors of the patient were not
      included, and further attempts have been made to increase sensitivity and
      specificity (eg, Study on the Efficacy of Nosocomial Infection Control project,
      National Nosocomial Infection Surveillance System score); the American Society of
      Anesthesiologists preoperative assessment score and the operation duration for
      specific procedures were introduced into the system as risk stratifiers. Advances
      in immunology have identified new ways in which the surgeon can moderate the
      immune response (eg, hemorrhage and blood transfusion-induced immune
      suppression). The increased rate of resistance in enterococci and staphylococci
      has refocused attention on infection control in surgery. However, there are
      recent reports from both sides of the Atlantic indicating that guidelines for
      infection control and antibiotic policy have not become reflected in standard
      procedures in many hospitals. New antibiotics may be developed, but resistance
      soon may follow. Sound techniques in surgery, with careful infection control and
      antibiotic policies, may be the only strategy to prevent further increases in
      resistance of pathogens in postoperative infections.

PMID- 9181406
TI  - The conflict between 'new nursing' and 'scientific management' as perceived by
      surgical nurses.
AB  - Nursing on surgical wards is a major area of employment for nurses, but the
      literature is sparse in relation to this group. Dramatic alterations in surgical
      care have occurred over the past few years, including the introduction of day
      surgery on a major scale, increased technical equipment and faster 'throughput'
      of patients. This has led to Nicholas Fox describing 'a conveyor belt of
      surgery'. These changes are occurring alongside major evolution within the
      nursing profession. Nurses are encouraged to give holistic, individualized care
      in what has been termed the 'new nursing' movement. This study addresses the
      problem of how nurses resolve these two conflicting discourses. Following an
      initial phase of participant observation, 10 registered surgical nurses were
      interviewed using the techniques of career biography, critical incident analysis
      and informal interviews. Different interpretations by the key members of the 'new
      nursing' discourse have been identified. These have been termed the professional
      project discourse, the modernist discourse, and the traditionalist discourse.
      Various strategies are adopted by nurses to reduce cognitive dissonance caused by
      the two conflicting discourses. The most commonly used being rationalization
      about the need for emotional labour.

PMID- 9181407
TI  - Therapeutic touch, nursing practice and contemporary cutaneous wound healing
      research.
AB  - The nursing profession is and always has been at the cutting edge of research and
      development into innovative and effective methods to treat, manage and enhance
      wound regeneration. One such method which was developed specifically for nursing
      science is a non-invasive, easily administered technique known as therapeutic
      touch (TT). Although there have been numerous anecdotal reports over the last two
      decades attesting to the efficacy of TT for cutaneous wounds, there have been
      only five experimental studies to date which have examined the phenomena in a
      scientifically rigorous manner. These five studies utilized randomized, double
      blind, placebo controlled protocols to analyse the effect of an experimental
      derivative of TT-non-contact therapeutic touch (NCTT)-on the healing rate of
      surgically administered full thickness human dermal wounds. The experiments
      introduced many original concepts and approaches to healing research and nursing
      practice. The data from the five studies indicated a statistically significant
      accelerated rate of wound healing for the treatment group in the initial two
      experiments, and non-significant and reverse significant effects for the
      remaining three studies. Although, experimentally, these results are far from
      impressive, clinically, the significant results of the first two experiments
      should be enough to encourage the nurse clinician to explore and utilize a
      similar non-invasive TT treatment method for patients with dermal lacerations.
      While the results of the studies were inconsistent overall, the series of
      experiments nonetheless significantly expanded the theoretical boundaries and
      understanding of the TT process and, due to the rigorous, double-blind
      methodological protocols used, have established the critical groundwork and
      guidelines for future nursing science research in the area.

PMID- 9181409
TI  - Developing the reflective teacher.
AB  - The conceptual issues and research findings surrounding the meaning and use of
      reflection are examined in this paper and serve as a foundation for discussing
      significant assumptions and beliefs regarding the use of reflection in nursing
      education. The strengths and limitations of reflection are discussed. The paper
      links current knowledge about reflection to the development of reflective
      thinking and its use by nurse educators and suggests strategies to enhance this
      development.

PMID- 9181408
TI  - Professionalism and community psychiatric nursing: a case study of four mental
      health teams.
AB  - In this paper I report on a 2-year study of the professional status of 10
      psychiatric nurses, working in four community mental health teams. The focus of
      the research was directed towards identifying the levels of clinical autonomy
      experienced by psychiatric nurses working in these teams. Diary-interview
      schedules were used to record how new clients were processed by the psychiatric
      nurse. The other members of the teams were interviewed (as were the managers to
      whom the nurses were accountable), using focused-interview schedules. The
      quantitative data from the diary-interview schedules were analysed using the
      Statistical Package for the Social Sciences. An adapted form of the technique
      advocated by Burnard was used to analyse qualitative data extracted from the
      diary-interview schedules and the focused-interviews. Conclusions from the
      research indicated that the nurses experienced a high degree of de facto clinical
      autonomy, which was characterized by unsupervized and arbitrary decision-making
      processes. In order to protect the user of mental health services, it is
      recommended that the espoused occupational strategy of professionalization for
      community psychiatric nurses is reconsidered.

PMID- 9181410
TI  - Perceived stressors and coping strategies among individuals with rheumatoid
      arthritis.
AB  - The purpose of this study was to identify the stressors perceived by individuals
      with rheumatoid arthritis (RA) and to describe coping strategies used to cope
      with illness-related stressors and their perceived effectiveness. Data were
      collected from 53 patients attending a rheumatology clinic. Results revealed that
      pain was the predominantly perceived stressor followed by limitation in mobility,
      difficulties in carrying out activities of daily living, helplessness, dependency
      on others, threat to self-esteem, interference in social activity, interference
      in family relationships, difficulties performing at work, and discomfort of the
      treatment. Subjects used optimistic and confrontive coping strategies more
      frequently than other coping strategies and optimistic coping strategies were
      perceived to be most effective. Point biserial correlation revealed a number of
      significant relationships between specific stressors and use of coping
      strategies: interference in family relationships and use of evasive coping
      strategies (r = 0.27, P < 0.05), and threat to self-esteem and use of both
      evasive (r = 0.45, P < 0.01) and emotive (r = 0.28, P < 0.01) coping strategies.
      Similarly, a number of significant relationships were found between specific
      stressors and the effectiveness of the coping strategies: interference in family
      relationships and the effectiveness of both evasive (r = 0.31, P < 0.05) and
      emotive (r = 0.38, P < 0.01) coping strategies, and threat to self-esteem and the
      effectiveness of emotive coping (r = 0.29, P < 0.05).

PMID- 9181411
TI  - Development and testing of the ethical reasoning tool (ERT): an instrument to
      measure the ethical reasoning of nurses.
AB  - Ascertaining the thinking of professionals as they are confronted with ethical
      practice issues is a prerequisite to understanding ethical decision making.
      Before researchers or educators can examine the effectiveness of various
      approaches to ethics teaching and learning, there is a need for reliable and
      valid tools to assess practitioners' cognition. A potential problem with the few
      measuring instruments currently available is the fact that they ask subjects to
      rank order existing lists of issues. This says little about an individuals' own
      thinking about ethical issues and may prompt thinking or responses which would
      not otherwise have occurred. This paper reports the results of a study to test
      the psychometric properties of a new instrument, the Ethical Reasoning Tool (ERT)
      that measures ethical reasoning of nurses. The ERT demonstrates a promising way
      to reveal unprompted ethical thinking about a practice dilemma, thereby
      clarifying 'real' versus 'assumed' professional reasoning. The tool allows nurse
      educators to identify areas of student learning/reasoning deficiency that can be
      addressed by educational interventions. The ERT also allows nurse educators to
      evaluate the effectiveness of nursing ethics study units in a trustworthy way.

PMID- 9181412
TI  - Confidentiality and the acquired immune deficiency syndrome (AIDS): an analysis
      of the legal and professional issues.
AB  - Confidentiality is one of the most significant concepts in health care and
      nursing practice, particularly in the arena of HIV infection and AIDS. The
      implications for individuals of deliberate or accidental disclosure of their HIV
      status can and does have far reaching effects. This paper will explore the
      concept of confidentiality by discussing the legal and professional issue of
      confidentiality and AIDS. The nature of the law and guidance by professional
      bodies allow exceptions to the respect of confidentiality in certain situations.
      AIDS and the need for confidentiality often is in conflict when public health
      considerations are deemed to be involved. The law is poorly developed in this
      area and often professional guidance is less than clear.

PMID- 9181413
TI  - An investigation into whether nursing student alter their attitudes and knowledge
      levels regarding HIV infection and AIDS following a 3-year programme leading to
      registration as a qualified nurse.
AB  - The purpose of this study was to examine whether a 3-year programme of nursing
      studies enabled nursing students to graduate from the course with greater
      knowledge and more positive attitudes towards HIV infection and AIDS than when
      they began the course. Students on a maths and information technology course were
      used as controls. The study involved the use of a questionnaire which gathered
      information about students' experience, knowledge, attitudes and moral judgement
      regarding HIV infection and AIDS. The experimental hypothesis stated that nursing
      students would show a greater increase in knowledge and positive attitude change
      towards HIV infection and AIDS than maths students. The results showed
      significant differences between third year nursing students' knowledge about HIV
      and AIDS when compared with other groups but it was noted that knowledge levels
      for all groups was quite low. There was no difference between first and third
      year nursing students' attitudes and moral judgement about HIV and AIDS but there
      was a significant difference between nursing students and maths students. It was
      suggested that there is a need to modify nurse education programmes in order to
      have greater impact on this topic area.

PMID- 9181414
TI  - Informational needs of women with a recent diagnosis of breast cancer:
      development and initial testing of a tool.
AB  - This study developed and tested the Toronto Informational Needs Questionnaire
      Breast Cancer (TINQ-BC), a questionnaire designed to identify the information
      which women with a recent diagnosis of breast cancer need to deal with their
      illness. The 73-item questionnaire had content validity based on findings in the
      literature and opinions of expert oncology nurses. It was administered to 114
      women with a recent diagnosis of breast cancer during chemotherapy (n = 39),
      radiation therapy (n = 40) or surgery (n = 35). Item analysis determined that 51
      items in five subscales should be retained in the questionnaire. The subscales,
      labelled Disease, Investigative Tests, Treatments, Physical, and Psychosocial had
      good internal consistency reliabilities with Cronbach's alphas of 0.81 to 0.93.
      Informational needs of women were high with mean scores over 200 in a possible
      range of 51-255. Informational needs were greatest in either the Disease or
      Treatments subscales. Marital status, level of education, and level of income
      were not related to level of informational need. Younger women had a greater need
      for information than older women (r = -0.35, P = 0.003). The results suggest that
      information is important to help women with breast cancer manage their illness.
      Nurses should give women an opportunity to ask questions and be prepared to give
      accurate information.

PMID- 9181415
TI  - The nature of social support as experienced by women treated for breast cancer.
AB  - This paper deals with one aspect of a major study, namely the meaning of social
      support, a concept loosely used in research and by practitioners. Grounded theory
      was adapted and discourse analysis used to retrospectively analyse data collected
      for a previous study exploring health visitors' support of patients with breast
      cancer. Patients' diagrams of their social networks illustrated their perceptions
      of support and strain. Respondents indicated that they faced six threats to their
      identities associated with the breast cancer experience and perceived social
      support to be actions/attitudes from formal or informal sources which maintained
      or assisted changes to their established identities. Social support maintained
      identities for many respondents who wanted to 'get back to normal' in their
      relationships and in their work. Women also needed support to accept identity
      changes, for example, adapting to an uncertain future. This paper focuses on the
      effects of informal support on identity. Respondents identified seven main types
      of informal support from various sources. Larger social networks were more likely
      to provide the different types of support needed. However, social intimacy of
      close relationships maintained important aspects of women's identities and were
      indeed part of their identities. Respondents' social contacts sometimes perceived
      breast cancer as threatening to their own identities and were consequently
      unsupportive. Informal support was vital for respondents coping with breast
      cancer. Nurses should help patients maintain and create their own informal
      support during illness.

PMID- 9181416
TI  - Choosing the choices in the USA: examples in the maternity area.
AB  - The concept of choice has featured prominently in both the recent United Kingdom
      (UK) health care reforms and in the debate relating to the care of childbearing
      women. An invitation to the USA facilitated contemplation of the health care
      system on which the recent UK reforms have been modelled. The impact of the
      health system on mother's choices was a source of particular interest. The
      implications for midwives, their practice and their relationships with their
      clients and colleagues emerge clearly. It may be that the United States' model of
      health care does not answer the needs of the UK.

PMID- 9181417
TI  - Antenatal education--where next?
AB  - The history of antenatal education throws light on why contemporary class
      attenders represent only a particular section of the childbearing population.
      Since Victorian times, the non-availability of the women's network to middle
      class women has forced them to seek knowledge of their own bodies, confidence in
      their childbearing capacities and the support of other women through formal
      educational opportunities. Research suggests that antenatal classes often fail to
      provide women with a realistic account of birth and parenting to replace the
      lived experience of earlier decades and may not be facilitated in such a way as
      to create the support groups which class attenders so critically need. Teaching
      approaches often promote dependency amongst clients rather than nurturing the
      decision-making skills required by a consumer-driven maternity service.

PMID- 9181418
TI  - Cognitive behaviour therapy territory model: effective disputing approach.
AB  - This paper proposes a disputing model (territory model) which is particularly
      useful and effective for disputing clients who persistently hold on to their
      dysfunctional thinking and/or core irrational beliefs. Their 'stubbornness' to
      change is compounded by unhealthy negative emotions during sessions. The intense
      emotion makes it difficult to access the belief system, and therefore any attempt
      to dispute it often proves futile. This model advocates the shift of disputing
      onto a different 'territory/ground' where the client can be facilitated to
      acquire higher, abstract and objective thinking, and at the same time his/her
      emotional level is susceptible to rational and logical arguments. The new
      thinking would act as a catalyst for the client to reflect on his/her
      dysfunctional thought/irrational beliefs. In this paper, the author uses a case
      example to illustrate and discuss the ineffectiveness of the 'traditional' way of
      disputing the dysfunctional thinking/core beliefs of a difficult and emotional
      client. This is contrasted with the 'territory' model.

PMID- 9181419
TI  - Cognitive/concept mapping: a teaching strategy for nursing.
AB  - Cognitive/concept mapping is an educational strategy that takes into
      consideration the principles of educational psychology. The most important single
      factor that influences learning is what the learner already knows. Nursing
      students face a great need to understand the larger questions and problems of
      their chosen field. Unless there is understanding, students may only commit
      unassimilated data to short-term memory and no meaningful learning will occur.
      The purpose of the following paper is to present concept mapping as a
      learning/teaching strategy for nursing students and nursing faculty. Examples of
      maps will be presented along with suggestions about how they can be used to plan
      care for a particular client or to learn more about the nursing care of a
      specific disease process.

PMID- 9181420
TI  - A self-assessment tool to measure older adults' perceptions regarding physical
      fitness and exercise activity.
AB  - The purpose of this research was to qualitatively generate and psychometrically
      assess an instrument which assesses the self-perceived physical fitness and
      exercise activity levels of community-dwelling older adults and examines
      perceived factors which enhance or impede their exercise activity level. This
      research was carried out in two stages: qualitative and quantitative. Items for
      the instrument were generated through qualitative interviews with 23 community
      dwelling older adults, 9 males and 14 females, with an age range of 63 to 82
      years. From this qualitative study, 50 items were generated, representing nine
      categories of elements which enhance or impede physical activity. The 50 items
      were incorporated into a 4-point, forced-choice, Likert format instrument which
      was pilot tested for clarity and ease of administration with a convenience sample
      of community-dwelling older adults. Following the pilot testing, 41 items were
      retained. The 41-item instrument, entitled Physical Fitness and Exercise Activity
      Levels of Older Adults Scale, was categorized into the following subscales:
      Physical Fitness, Barriers, Motivators, and Exercise Frequency. Initial testing
      of the Physical Fitness and Exercise Activity Levels of Older Adults Scale seems
      to indicate adequate validity and reliability. Correlation coefficients for the
      total instrument, as well as the subscales, were significantly positive for both
      stability and internal consistency. Results with respect to predictive validity
      were mixed. The Physical Fitness and Motivators subscales were significant
      predictors of Exercise Frequency. Although the correlation between the Barriers
      subscale and Exercise Frequency was negative, it was non-significant.

PMID- 9181421
TI  - Alcohol use amongst community-dwelling elderly people: a review of the
      literature.
AB  - Alcohol use amongst elderly people is an increasingly important area to
      understand, yet relatively little research has been undertaken and our knowledge
      remains limited. This paper contains a review of the literature, concentrating on
      alcohol use in community-dwelling elderly people. Both cross-sectional and
      longitudinal research papers are reviewed; their findings suggest high abstinence
      rates amongst the population under consideration, with consumption consistently
      associated negatively with increasing age and female gender. A summary of the
      largely non-specific, descriptive literature available is also included. Research
      concerned with elderly people and alcohol use is problematic and therefore the
      limitations of the available research are examined in detail. Firm conclusions
      are difficult to draw from the research to date because, for example, there are
      varying definitions of terms such as 'alcoholism' and 'heavy drinking' and
      instruments used for detection have not been validated with older age groups. The
      need for increased awareness amongst health professionals, especially nurses,
      about issues surrounding community-dwelling elderly people and alcohol use and
      misuse is discussed. Finally, the importance of further research, especially
      amongst largely neglected groups of the elderly population, such as ethnic
      minority groups and elderly homeless people, is suggested.

PMID- 9181422
TI  - The problems of elderly people at home one week after discharge from an acute
      care setting.
AB  - The problems of elderly people following discharge from hospital is a worldwide
      focus of nursing attention. Actual and local insight into the nature and extent
      of post-discharge problems is needed as a base for improving and evaluating
      discharge planning. Problems following discharge were investigated as the first
      part of a larger study. Over a 3-month period, 251 elderly people who had been
      discharged after a hospital stay of more than 3 days, were asked to participate
      in the study. Half received a postal questionnaire and half were interviewed at
      home, one week after discharge. There were 145 respondents. The need for
      information was mentioned by 80% of the patients. Housekeeping tasks also caused
      most patients some difficulty. Almost 40% of those discharged reported some kind
      of unmet need.

PMID- 9181423
TI  - Patients' perceptions of their education needs in the first six weeks following
      discharge after cardiac surgery.
AB  - The aim of this study was to discover what information and support patients feel
      they need in the 6-week rehabilitation period following discharge after cardiac
      surgery. It was undertaken at the request of the hospital multidisciplinary
      cardiac rehabilitation team to enable them to plan a package of information to
      meet those needs. It was a local study aiming to gain insight into the patients'
      own views by asking them to keep a diary over the 6-week period and then take
      part in an unstructured interview when they returned for their 6-week out-patient
      appointment. The analysis of the respondents' comments gave an insight into their
      whole experience of the first 6 weeks following discharge. The themes which
      emerged were wide-ranging and were grouped under the headings of the early
      discharge needs of pain relief and sleep promotion, psychological needs,
      practical needs and community support. To take the study forward, several
      recommendations were made to improve the rehabilitation experience. These
      included additions to the literature and patient education sessions, and changes
      to ensure a smoother transition into the community. The findings also suggest the
      need for improvements in and further research into the whole area of the
      psychological preparation for discharge after cardiac surgery.

PMID- 9181424
TI  - Long-term indwelling urinary catheter care: conceptualizing the research base.
AB  - The traditional public health concepts of agent, host, and environment can
      provide a useful interdisciplinary model for analysing the current state of
      knowledge in long term indwelling urinary catheter care. A broad review of
      literature about urinary catheter care was carried out to identify major areas of
      research and gaps in knowledge. Most research in the past decade has focused on
      understanding how catheter encrustations develop and how such encrustations may
      contribute to leaking/blocking of the catheter and urinary tract infection. Two
      tables are presented which summarize research related to the development of
      sediment/encrustation of the catheter and to irrigation of the catheter.
      Nevertheless, many areas related to catheter care have not been studied
      extensively. The patient's perspective is one such area. Other areas that have
      not been studied in depth include care of the drainage bag and the role of fluid
      intake. These under-studied concerns relate to environmental factors with which
      the nurse is directly involved, namely, asepsis and hydrokinetic forces. Further
      conceptualization of the nursing role in long-term urinary catheter care might
      aid in the development of nursing theories that could be tested to understand how
      best to help people manage these catheters.

PMID- 9181425
TI  - Development of a tool to rate the quality assessment of randomized controlled
      trials using a Delphi technique.
AB  - The aim of this study was to develop a quality of study tool rate the
      methodological quality of individual primary randomized controlled trials (RCTs)
      to be included in a meta-analysis. A Delphi-technique using several rounds of
      questions to seek consensus, among trialists, on criteria important in a RCT was
      used. Eight trialists formed the Delphi panel. The developed quality of study
      tool consisted of 53 items in 15 dimensions. The tool was tested for reliability
      and validity. Unlike many other quality assessment tools, the developed tool may
      be used to rate numerically each primary study. This is important in reviews or
      in meta-analyses where one objective may be to ascertain whether those studies of
      a higher quality exhibit different results to reviewing studies of lower quality.
      The tool needs further testing.

PMID- 9181426
TI  - Addressing barriers: disabled rights and the implications for nursing of the
      social construct of disability.
AB  - Drawing upon the writings of disabled people, this paper explores some of the
      issues which nurses working with disabled people are trying to address, in
      particular the barriers model of disability. Traditionally disability has been
      regarded as a personal tragedy afflicting the individual, hence the response to
      disability has been via the charity, health and welfare systems. Disabled people
      over the past two decades have substantially challenged this view of disability
      and the responses it prompts, arguing that disability is created by social
      barriers and barriers in the built environment. This requires a different
      response. Nurses working with disabled people, such as learning disability
      nurses, have struggled to develop more appropriate responses to disability, for
      example by developing working alliances with people with learning difficulties in
      order to both promote health and address disabling barriers. The issues these
      nurses face and some of the lessons disabled people have taught them are relevant
      to the nursing profession's wider struggle to shed its medical and dependency
      image.

PMID- 9181427
TI  - Hong Kong nurses' health-related behaviours: implications for nurses' role in
      health promotion.
AB  - The health-related behaviors of a random sample (n = 92) of Hong Kong nurses were
      assessed by a questionnaire written either in English or in English and Chinese.
      Hong Kong nurses reported negligible smoking or alcohol use, low levels of breast
      self-examination, cervical screening behaviour and regular exercising, seat belt
      use and driving within the speed limit. The sample reported high levels of making
      efforts to avoid foods high in cholesterol, eating foods high in fibre and eating
      fruit daily. Dental hygiene was reported to be high. Just over half the sample
      reported sleeping 7-8 hours each night and eating breakfast daily. Most nurses
      reported maintaining their body weight at a healthy level and eating snacks
      between meals. The English language version of the questionnaire produced a
      slightly better response rate than the bilingual questionnaire. The results are
      discussed with reference to previous studies of females' health-related
      behaviours in Hong Kong and elsewhere. The implications for Hong Kong nurses'
      role in health promotion is discussed.

PMID- 9181428
TI  - Nurses' attitudes towards suicidal behaviour--a comparative study of community
      mental health nurses and nurses working in an accidents and emergency department.
AB  - The purpose of this study was to explore and compare the attitudes towards
      suicidal behaviour of community mental health nurses (CMHNs) and registered
      nurses working in an accidents and emergency (A&E) department. The sample
      consisted of 80 nurses working in the same locality. An instrument was designed
      using statements from Domino's 'Suicide Opinion Questionnaire' (SOQ) and new
      statements based on a comprehensive survey of research in this area. The
      instrument contained four attitudinal categories consisting of; acceptability;
      morality and mental illness; professional role, work and care; and communication
      and attention. Results reveal that both groups of nurses held generally positive
      attitudes towards suicidal behaviour, contrasting with previous studies where
      more negative attitudes amongst nurses were found. A t-test showed no
      statistically significant differences between the two groups of nurses in any of
      the four attitudinal categories. Attitudes were significantly different in
      accordance with nurses' length of experience and age within both groups. Further
      research is needed in this area if nurses are to develop their role alongside
      other professionals working towards the objectives of suicide prevention
      policies.

PMID- 9181429
TI  - Health promotion ideology and nursing education.
AB  - Nursing has been concerned primarily with the visible aspects of health promotion
      and has shown little regard for what is invisible. Yet the hidden ideology
      powerfully shapes current approaches to health promotion. This paper examines and
      makes visible the ideology of individual responsibility which is embedded in
      individualistic health promotion, the primary orientation to health promotion.
      Ways in which this ideology is perpetuated within nursing curricula are
      described. Concrete strategies are proposed that may be considered by nurse
      educators as they seek to prepare students in health promotion, with particular
      emphasis on strategies that highlight its ideological underpinnings.

PMID- 9181430
TI  - Undergraduate nursing students' perceptions of their clinical learning
      environment.
AB  - The clinical learning environment (CLE) is an interactive network of forces
      influencing student learning outcomes in the clinical setting. This study used
      mixed methods to identify factors characterizing students' perceptions of the
      CLE. The sample consisted of 229 undergraduate students in the second or third
      year of their biophysical nursing strand. The five subscales of the Clinical
      Learning Environment Scale, 'staff-student relationships', 'nurse manager
      commitment', 'patient relationships', 'student satisfaction' and 'hierarchy and
      ritual', were supported by qualitative data obtained from student interviews.
      Interpersonal relationships between the participants in the CLE were crucial to
      the development of a positive learning environment. Student satisfaction with the
      CLE was both a result of, and influential in creating, a positive learning
      environment. Nurse educators, clinical venues, and all others participating in
      the undergraduate nursing students' clinical education, must collaborate in order
      to create a CLE which promotes the development of well-educated registered nurses
      capable of providing safe, cost-effective patient care.

PMID- 9181431
TI  - Nurse researcher: a study of a contradiction in terms?

PMID- 9181432
TI  - Quantitative analysis of Drosophila period gene transcription in living animals.
AB  - To determine the in vivo regulatory pattern of the clock gene period (per), the
      authors recently developed transgenic Drosophila carrying a luciferase cDNA fused
      to the promoter region of per. They have now carried out noninvasive, high time
      resolution experiments allowing high-throughput monitoring of circadian
      bioluminescence rhythms in individual living adults for several days. This
      immediately solved several problems (resulting directly from individual
      asynchrony within a population) that have accompanied previous biochemical
      experiments in which groups of animals were sacrificed at each time point.
      Furthermore, the authors have developed numerical analysis methods for
      automatically determining rhythmicity associated with bioluminescence records
      from single flies. This has revealed some features of per gene transcription that
      were previously unappreciated and provides a general strategy for the analysis of
      rhythmic time series in the study of molecular rhythms.

PMID- 9181433
TI  - Aftereffects of entrainment on the period of the pacemaker in the eye of the
      mollusk Bulla gouldiana.
AB  - The authors examined the "aftereffects" of entrainment of Bulla gouldiana to 11 h
      light:11 h dark (LD 11:11) (T22) or LD 13:13 (T26) on the period (tau) of the
      circadian rhythm of impulse activity recorded in vitro from the eye in constant
      darkness. When both eyes remained attached to the cerebral ganglion, the average
      period was 23.9 +/- 0.62 h (mean +/- SD, n = 6) for animals from T22 and 24.9 +/-
      0.54 h for animals from T26. The 1-h difference between the periods of the T26
      and the T22 animals was significant (p < .01, t test). When eyes were isolated
      from the cerebral ganglion by severing the optic nerve, the difference in average
      period between eyes from T22 and eyes from T26 animals was 2.2 h (23.3 +/- 0.72 h
      [n = 7] vs. 25.5 +/- 0.62 [n = 6], p < .001). When eyes remained attached to the
      brain but uncoupled from the contralateral eye, the aftereffect of entrainment to
      non-24-h light cycles was intermediate. For T22 animals, tau was 23.9 +/- 0.29 h
      (n = 6), whereas for the T26 animals, tau = 25.2 +/- 0.48 h (n = 7). The results
      show that isolated eyes can express aftereffects and indicate that coupling
      between ocular pacemakers and efferent signals from the cerebral ganglion
      diminish the effects of entrainment on the free-running period of the rhythm from
      the eye.

PMID- 9181434
TI  - Suprachiasmatic nuclei lesions do not eliminate homeostatic thermoregulatory
      responses in rats.
AB  - Electrolytic lesions aimed at the suprachiasmatic nuclei (SCN) were made in male
      Long-Evans rats. Body temperature (Tb), activity, and drinking were monitored
      continuously in a 12-h light:12-h dark (12:12 LD) cycle at an ambient temperature
      of 23 degrees C. Large SCN lesions eliminated activity and drinking rhythms and
      abolished or reduced the circadian rhythm of Tb. The Tb responses of the rats
      were measured in L after exposure to cold and injection of lipopolysaccharide
      (LPS), a fever-producing drug, and in both L and D during a 30-min exposure to a
      novel cage. Rats with SCN lesions (SCNX) maintained their Tb as well as did
      controls during 2-h exposure to 2 degrees C. They also showed the expected
      increases in Tb in response to novelty and LPS. Nevertheless, there were
      differences between SCNX rats and other rats. When measured 9 h after LPS
      injection, SCNX rats had lower Tb in D than did sham-lesioned or intact rats or
      rats with lesions that missed the SCN. This is not surprising; the Tb of SCNX
      rats does not go as high as that of intact rats in D. However, it was surprising
      that at night SCNX rats increased their Tb in response to novelty (lights on in
      the test situation), whereas normal rats did not. For some reason, light inhibits
      the Tb rise to novelty in normal rats but does not do so in rats with SCN
      lesions.

PMID- 9181435
TI  - Lesion of the serotonergic terminals in the suprachiasmatic nuclei limits the
      phase advance of body temperature rhythm in food-restricted rats fed during
      daytime.
AB  - The daily rhythm of body temperature was recorded in control rats fed ad libitum
      and subsequently fed during daytime 50% of ad libitum food intake. Aside from the
      expression of a feeding-associated component, body temperature rhythm was phase
      advanced (7 h) by a timed caloric restriction; the new plateau of the acrophase
      of the nocturnal peak was close to the light-dark transition. A lesion of
      serotonergic (5-HTergic) terminals in the suprachiasmatic nuclei (SCN)-the
      endogenous circadian clock(s)-was performed by microinjection of the 5-HT
      neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). During the ad libitum-fed state,
      the acrophase of body temperature rhythm was not modified by the 5,7-DHT
      treatment. In response to a timed caloric restriction, however, the phase advance
      of the nocturnal peak of body temperature rhythm was reduced by 2 h in rats with
      5,7-DHT lesions as compared to that of sham-operated rats. Magnitude and day
      night pattern of wheel-running activity between the two groups of rats also were
      analyzed. No intergroup difference was found in the amount of wheel-running
      activity prior to the time of feeding. Moreover, the phase advance of nocturnal
      component of locomotor activity rhythm observed toward the time of feeding in
      sham-operated rats was limited by 5,7-DHT treatment. It is concluded that the
      photic synchronization of body temperature rhythm does not depend on the 5
      HTergic projection to SCN under ad libitum conditions. By contrast, the phase
      advancing property of a timed caloric restriction on the daily rhythm of body
      temperature is mediated by a neuronal circuit involving the 5-HTergic projection
      to SCN. That the phase advance was not fully eliminated by 5,7-DHT treatment
      suggests that other pathways participate in this mediation.

PMID- 9181436
TI  - Sleepiness, performance, and neuroendocrine function during sleep deprivation:
      effects of exposure to bright light or exercise.
AB  - The temporal profiles of subjective fatigue (as assessed by the Stanford
      Sleepiness Scale), of cognitive performance (on a digit symbol substitution test
      and a symbol copying task), of body temperature, and of the peripheral
      concentrations of melatonin, thyroid-stimulating hormone (TSH), and cortisol were
      obtained simultaneously at frequent intervals in 17 normal young subjects
      submitted to a 43-h period of constant routine conditions involving continuous
      wakefulness at bed rest in dim indoor light. The subjects had knowledge of time
      of day. Caloric intake was exclusively in the form of an intravenous glucose
      infusion, and plasma glucose levels were monitored continuously in 8 of the 17
      subjects. Under these conditions, fluctuations in plasma glucose reflect
      primarily changes in glucose use because endogenous glucose production is
      suppressed by the exogenous infusion. Following the completion of a baseline
      constant routine study, the volunteers participated in two subsequent studies
      using the same protocol to determine the immediate psychophysiological effects of
      exposure to a 3-h pulse of bright light or to a 3-h pulse of physical exercise.
      Sleepiness and performance varied in a mirror image, with significant negative
      correlations. Sleepiness scores were minimal around noon and then increased at a
      modest rate throughout the rest of the normal waking period. Staying awake during
      usual bedtime hours was associated with an acceleration in the rate of increase
      in sleepiness, which coincided with decreasing body temperature, rapidly rising
      cortisol concentrations, and maximal levels of melatonin and TSH. When body
      temperature reached its nadir, a further major increase in sleepiness occurred in
      parallel with a pronounced decrease in plasma glucose (reflecting increased
      glucose use). Recovery from maximal sleepiness started when blood glucose levels
      stopped falling and when significant decreases in cortisol and melatonin
      concentrations were initiated. Lower levels of subjective sleepiness resumed when
      glucose concentrations and body temperature had returned to levels similar to
      those observed prior to sleep deprivation and when melatonin and TSH
      concentrations had returned to daytime levels. The synchrony of behavioral,
      neuroendocrine, and metabolic changes suggests that circulating hormonal levels
      could exert modulatory influences on sleepiness and that metabolic alterations
      may underlie the sudden increase in fatigue consistently occurring at the end of
      a night of sleep deprivation. Effects of bright light or exercise exposure on
      subjective sleepiness appeared to be critically dependent on the timing of
      exposure.

PMID- 9181437
TI  - The effects of evening bright light on next-day sleep propensity.
AB  - The present study investigated the effects of evening bright light (BL) compared
      to dim light (DL) on next-day sleep propensity as well as the acrophase of oral
      temperature and mood scores. A total of 12 male subjects (mean age 23.5 +/- 2.6
      years) were exposed to 2 h of evening DL or BL 30 min after sunset for 5
      consecutive days. The experimental period started after the 5th day of exposure.
      After light exposure, subjects remained awake in the sleep laboratory until 07:00
      h, when they began the 7/13 ultrashort sleep-wake paradigm, which continued for
      24 h until 07:00 h the next day. Oral temperature was measured hourly. The
      results showed that evening exposure to BL, in comparison to DL, significantly
      delayed the next-day sleep gate as well as the acrophase of the oral temperature
      curve and the acrophase of negative mood. The effects of BL on the next-day
      distribution of sleep stages showed an increase of Stage 2 and less REM (rapid
      eye movement) during the morning. The results indicate that sleep propensity is
      regulated by a circadian pacemaker that is responsive to evening BL exposure.

PMID- 9181438
TI  - Estimating the endogenous circadian temperature rhythm without keeping people
      awake.
AB  - This study was concerned with estimating endogenous temperature rhythms without
      imposing sleep deprivation. The aim of Experiment 1 was to quantify the masking
      effect on the circadian temperature rhythm in a group of 18 healthy young
      subjects (8 women and 10 men, ages 19-29 years). Temperature data collected under
      a 36-h wakeful bed rest protocol were used as a marker of the endogenous
      component of the rhythm ("unmasked rhythm"), and temperature data collected under
      24 h of a normal nycthemeral routine (immediately before the bed rest protocol)
      were used as the "masked" rhythm. An algorithm to "demask" the temperature data
      collected under the nycthemeral condition was then developed, based on the
      differences observed between the temperature data collected under wakeful bed
      rest and nycthemeral conditions. The consistency of the demasking technique was
      tested in Experiment 2, using the same parameters on a group of 19 healthy
      elderly subjects (8 women and 11 men, ages 78-88 years) who also had experienced
      both nycthemeral and wakeful bed rest conditions. The demasking technique was
      evaluated both by comparing nycthemeral, demasked, and unmasked temperature
      rhythms themselves and by comparing individual estimates of circadian phase and
      amplitude that had been gleaned from them. In comparison to the unmasked
      condition, the nycthemeral condition showed lower mean nighttime temperature,
      earlier mean phase estimates, and higher mean amplitude estimates in both young
      and elderly subjects. Following application of the demasking procedure to the
      nycthemeral temperature data, mean demasked temperature curves were closely
      comparable to mean unmasked temperature curves in both young and elderly
      subjects. Phase and amplitude estimates derived from the demasked temperature
      data also were highly comparable to those in the unmasked conditions. Thus, this
      demasking procedure appears to be a useful tool in estimating the endogenous
      temperature rhythm and appears to work equally well for young and elderly
      subjects.

PMID- 9181439
TI  - An approach to studying circadian rhythms of adolescent humans.
AB  - The "long nights" protocol was designed to evaluate sleep processes and circadian
      rhythm parameters in young humans. A total of 19 children (10 boys, ages 11.2 to
      14.1 years [mean = 12.7 +/- 1.0], and 9 girls, ages 12.2 to 14.4 years [mean =
      13.1 +/- 0.7]) took part in the study. Sleep/wake initially was assessed at home
      using actigraphy and diary for 1 week on each child's self-selected schedule
      followed by an 8-night fixed light-dark (LD) condition, while sleeping from 22:00
      to 08:00 h and wearing an eye mask to exclude as much light as possible. Phase
      measurements included 4-night mean actigraphically estimated sleep onset and
      offset as well as 1-night dim light salivary melatonin onset (DLSMO) phase at the
      end of each condition. Subjects then lived in the laboratory for 6 consecutive
      cycles: Day 1 LD = 14:10 h, lights out 22:00 to 08:00 h; Days 2-4 LD = 6:18 h,
      lights out 18:00 to 12:00 h; Days 5-6 = constant routine in continuous dim light
      (about 20 lux); Night 6 = 14 h recovery sleep. Phase markers (sleep onset, sleep
      offset, DLSMO) were significantly less dispersed after the fixed LD as compared
      to the self-selected condition, indicating efficacy of the LD protocol. Phase
      markers were correlated at the self-selected assessment (sleep onset vs. sleep
      offset r = .72; DLSMO vs. sleep onset r = .82; DLSMO vs. sleep offset r = .76)
      but not on the fixed schedule, probably due to restricted range. The constant
      routine provided additional phase markers, melatonin offset and midphase. Offset
      phase of melatonin secretion was significantly correlated with age (r = .62) and
      Tanner stage (r = .62). In conclusion, these preliminary data indicate a
      relationship between adolescent development and circadian phase. Thus, the long
      nights protocol is a feasible way in which to assess circadian parameters in
      young humans as well as to examine intrinsic sleep processes.

PMID- 9181440
TI  - An appeal to the readership regarding NIH/NIDDK funding for urologic research not
      related to cancer.

PMID- 9181441
TI  - Comparative follow-up of patients with acute and obtuse infundibulum-pelvic angle
      submitted to extracorporeal shockwave lithotripsy for lower caliceal stones:
      preliminary report and proposed study design.
AB  - Nowadays, there is a consensus that the poor success rate of extracorporeal
      shockwave lithotripsy (SWL) is in the treatment of lower caliceal stones. The
      gravity-dependent position of the lower-pole calices is postulated to be the main
      factor hindering the spontaneous passage of stone debris that results from SWL.
      Nevertheless, we proposed that there are some particular features of the inferior
      pole collecting system anatomy that could contribute to fragment retention. We
      studied the influence of the lower infundibulum-pelvic angle on fragment
      retention, considering 74 patients submitted to SWL for the treatment of lower
      pole nephrolithiasis in a Lithostar Plus machine. At a mean follow-up of 9
      months, 75% of the patients presenting an angle of greater than 90 degrees
      between the lower infundibulum where the stone was located and the renal pelvis
      became stone-free within 3 months. On the other hand, only 23% of the patients
      presenting an angle smaller than 90 degrees between the lower infundibulum where
      the stone was located and the renal pelvis became stone-free during the follow
      up. Determination of the angle between the renal pelvis and the infundibulum of
      the inferior pole calix where the stone is located is very important, because the
      angle will differ in the same kidney, depending on stone location. Although
      preliminary and based on a small series of patients, our data suggest that an
      acute pelvic-lower pole infundibular angle hinders the spontaneous discharge of
      fragments after SWL. Also, use of the proposed technique of pelvic-lower pole
      infundibular angle measurement will be important for unifying angle evaluation by
      other investigators.

PMID- 9181442
TI  - Bolus injection v drip infusion contrast administration for ureteral stone
      targeting during shockwave lithotripsy.
AB  - Intraoperative excretory urography may be used to facilitate stone targeting
      during in situ SWL for ureteral stones, precluding the need for ureteral catheter
      placement. We compared bolus injection with drip infusion urography for efficacy
      in stone localization. Twenty-seven patients with normal renal function and a
      solitary, difficult to visualize, radiopaque ureteral calculus were randomized to
      receive intravenous contrast by either bolus injection (N = 13) or drip infusion
      (N = 14). The bolus injection patients received an average of 74 mL of Conray 400
      contrast over 1 minute; the drip infusion patients received an average of 92 mL
      of contrast over 15 minutes. After bolus injection, it took an average of 12
      minutes to opacify the ureter compared with 14 minutes after drip infusion (P =
      0.62). It took longer to initiate (5 minutes) and complete (6 minutes) treatment
      after drip infusion than after bolus injection (P = 0.28 and P = 0.16,
      respectively). Imaging time was significantly longer in the infusion group than
      in the bolus group (12 v 7 minutes; P = 0.04). Stone-free rates were similar in
      the two groups: 100% for the bolus group and 91% for the infusion group. No
      patient in either group experienced an adverse reaction to the contrast. Overall,
      the two methods of contrast administration were equally efficacious for stone
      targeting during SWL. However, bolus injection required lesser amounts of
      contrast, provided more rapid opacification of the ureter, and resulted in an
      overall shorter procedural time, although the only statistically significant
      differences were in imaging time and contrast volume.

PMID- 9181443
TI  - Extracorporeal shockwave lithotripsy for urinary calculi in autosomal dominant
      polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic
      disorder. Renal stones have a high rate of occurrence among patients with ADPKD
      and are a significant cause of morbidity in this disorder. Thirteen patients with
      ADPKD and symptomatic or obstructive renal stones presented to our hospital for
      evaluation and treatment with extracorporeal shockwave lithotripsy (SWL). A total
      of 16 renal units were treated. The auxiliary procedures included placement of a
      double-J stent in nine kidneys when the stone was larger than 8 mm in diameter.
      Eleven patients (85%) were stone free 3 months after lithotripsy; a second
      treatment was necessary in two patients. We conclude that SWL can be used as a
      primary management tool for renal stones in patients with ADPKD.

PMID- 9181444
TI  - The Hickman peel-away sheath: alternative for pediatric percutaneous
      nephrolithotomy.
AB  - Percutaneous nephrolithotomy presents a therapeutic challenge in children because
      of the disproportion between the sizes of the instruments and the kidneys. A
      technique for pediatric nephrolithotomy used on a 2-year-old female child is
      presented. The patient was born prematurely and developed kidney stones as a
      complication of furosemide therapy. She failed medical management with
      hydrochlorothiazide, and the stone did not disintegrate following extracorporeal
      shockwave lithotripsy (ESWL). A Chiba needle was used to access the renal
      collecting system percutaneously. Using a guidewire, sequential dilatation was
      performed to 16F. A 15F Hickman catheter introduction kit was then used, and the
      sheath was partially peeled away. A 10F pediatric cystoscope and grasper were
      inserted through the sheath to remove the stones. A 12F catheter was then placed
      through the sheath; the sheath was peeled away, and the catheter was left
      indwelling for 48 hours. No complications ensued. A postoperative nephrostogram
      showed free drainage and absence of residual stones. Utilization of the Hickman
      peel-away sheath constitutes an excellent alternative nephrolithotomy technique
      for children with stones unresponsive to more conservative treatment.

PMID- 9181445
TI  - Holmium: YAG laser damage to ureteral guidewire.
AB  - The holmium:yttrium-aluminum-garnet (holmium:YAG) laser effectively fragments
      urinary calculi of all compositions. Complications have been minimal and mostly
      attributable to the ureteroscopy as opposed to the laser. We report a case in
      which the polytetrafluoroethylene (PTFE) coating of a ureteral guidewire was
      broken with the holmium:YAG laser and remained in the collecting system after the
      guidewire was removed postoperatively. The patient required cystoscopy to remove
      the guidewire coating.

PMID- 9181446
TI  - Effect of mineral oil on porcine urothelium.
AB  - Mineral oil has been used to facilitate ureteral stone extraction and to treat
      selected patients with infected residual urine. The purpose of this study was to
      evaluate the effect of mineral oil on the urothelium. Twelve adult female farm
      pigs underwent bilateral ureteral catheter placement under general endotracheal
      anesthesia. Retrograde pyelograms were performed and the ureteral diameters
      measured. Using a randomization protocol, six animals underwent injection of 10
      mL of normal saline into one ureteral catheter and 50 mL of normal saline
      instillation into the bladder. In the remaining six animals, 10 mL of mineral oil
      was injected into one ureteral catheter and 50 mL of mineral oil into the
      bladder. The instillation was maintained for 30 minutes, and then the catheters
      were removed. One week later, under general endotracheal anesthesia, cystoscopy
      and retrograde pyelography were performed to measure the diameter of the ureters,
      and the animals were euthanized. The bladder, ureters, and kidneys were harvested
      for macroscopic and histopathologic evaluation. There was no significant
      difference in the diameter of the ureters injected with normal saline, the
      uninjected ureters, or the mineral oil-injected ureters. The bladders, ureters,
      and kidneys were grossly normal in all animals. No significant histopathologic
      changes were noted in the ureteral or bladder urothelium or the renal parenchyma
      in the animals injected with mineral oil. In conclusion, the instillation of
      mineral oil within the urinary tract does not have any significant long-term
      functional or histopathologic effect on the urothelium.

PMID- 9181447
TI  - Laparoscopic nephrectomy of a horseshoe kidney.
AB  - The role of laparoscopic surgery in the treatment of benign renal diseases
      continues to evolve with the development of equipment and refinement of
      techniques. A minimally invasive approach to the treatment of these lesions
      offers several advantages, including shorter convalescence. We describe the first
      laparoscopic nephrectomy involving a horseshoe kidney.

PMID- 9181448
TI  - Effects of carbon dioxide pneumoperitoneum in pigs with impaired pulmonary
      function.
AB  - The objective of our study was to investigate the possible adverse hemodynamic
      effects of a CO2 pneumoperitoneum in an experimental model in pigs with impaired
      pulmonary function. Thirteen animals were anesthetized with azaperon/ketamine and
      ventilated with 67% nitrous oxide in oxygen. By intravenous injection of dextran
      microspheres, a capillary pulmonary embolism was induced. After embolization,
      three animals served as controls (Group 1), five underwent open nephrectomy
      (Group 2), and five underwent laparoscopic nephrectomy (Group 3). Intra-abdominal
      pressure was kept constant at 15 mm Hg. At intervals, hemodynamic parameters were
      measured, and blood gas measurements were performed. Data were analyzed using a
      general linear model analysis of variance for differences between groups, and a
      paired t-test was applied for differences within groups from one condition to the
      next. The groupwise comparison revealed a significant rise of cardiac output in
      the laparoscopy group compared with the open nephrectomy group. No differences
      were noted for heart rate, systemic arterial pressure, central venous pressure,
      mean pulmonary arterial pressure, or pulmonary arterial wedge pressure.
      Impairment of pulmonary function caused no negative hemodynamic effect during
      laparoscopic nephrectomy.

PMID- 9181449
TI  - High-intensity focused ultrasound ablation of the kidney in a large animal model.
AB  - The purpose of this study was to establish the feasibility of noninvasive
      treatment of small renal tumors with high-intensity focused ultrasound (HIFU). A
      1.69-MHz extracorporeal HIFU transducer of 150-mm focal length was used. In vitro
      experiments with excised porcine kidneys allowed determination of suitable
      exposure parameters to be tested in vivo. For short exposure times (< 2 seconds),
      the minimum energy required to produce acute thermal damage was 500 +/- 100 Wcm-2
      per second. Porcine kidneys (N = 18) were treated in vivo at a depth of 40 mm
      from the skin surface, with acute damage detected in 13. Damage was
      macroscopically and histologically discrete and confined to the target area
      within the kidney. Skin induration was observed after treatment in nine cases,
      and there was one skin burn. Transducer developments to prevent this morbidity
      and to improve energy deposition within the target are discussed.

PMID- 9181450
TI  - High-intensity focused ultrasound energy for benign prostatic hyperplasia:
      clinical response at 6 months to treatment using Sonablate 200.
AB  - We evaluated the safety and efficacy of high-intensity focused ultrasound (HIFU)
      using a modified Sonablate 200 and compared the clinical response with that of
      the prototype Sonablate at 6 months after treatment. Since 1995, 35 patients ages
      66 +/- 7 years underwent HIFU with the Sonablate 200 for symptomatic benign
      prostatic hyperplasia (BPH) under low spinal anesthesia. The estimated prostatic
      volume was 40.4 +/- 4.8 cc before treatment. A silicon-coated 16F latex catheter
      was indwelling during determination of the therapy zone and treatment so that
      critical tissue at the midline was thoroughly treated. Twenty-two patients were
      analyzed with complete 6-month follow-up data. Side effects were transient
      urinary retention in four of these patients, hematuria in five, and hematospermia
      in eight. Peak urinary flow rate increased from 7.4 +/- 4.0 mL/sec to 11.4 +/-
      4.0 mL/sec (P < 0.001) (54% increase). During the same period, the mean
      International Prostatic Symptom Score decreased from 20.4 +/- 7.1 to 9.0 +/- 7.5
      (P < 0.001) (56% decrease). Quality of Life score improved from 5.4 +/- 0.6 to
      2.4 +/- 1.3 (P < 0.001). Magnetic resonance imaging by means of an endorectal
      surface coil revealed significant coagulative necrosis areas in the periurethral
      gland at 1 month on T2-weighted images. These data demonstrate that HIFU for BPH
      using the Sonablate 200 produced a better clinical response than the prototype
      Sonablate and is expected to provide long-term durability of the response.

PMID- 9181451
TI  - Endoscopic transvesico-transurethral approach for repair of vesicovaginal
      fistula: initial case report.
AB  - Through an endoscopic transvesico-transurethral approach, we closed a
      vesicovaginal fistula that occurred after hysterectomy in a patient with uterine
      leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was
      resected transurethrally and sutured in two layers through two 5-mm suprapubic
      trocars placed into the bladder and the urethral route under pneumobladder. The
      patient had no urine leakage from the vagina after surgery.

PMID- 9181452
TI  - Neodymium:YAG laser coagulation prostatectomy for patients in urinary retention.
AB  - Urinary retention necessitating catheterization is the presenting complaint for a
      significant minority of men requiring surgical therapy for bladder outlet
      obstruction. A total of 67 men presented in acute or chronic urinary retention
      and underwent Nd:YAG laser prostatectomy. Their mean age was 71 years, the mean
      estimated excess transition zone tissue was 40 g, and the mean laser energy
      delivery was 48 kJ. The median postoperative catheterization time was 10 days.
      Five men required catheterization for > or = 6 weeks, and in five men, the
      catheter was removed within 48 hours. In four men (6%), a successful
      postoperative voiding trial was never achieved. Postoperatively, mean voiding
      measures for the remaining 63 men were a peak flow rate of 16.1 mL/sec, a post
      void residual volume of 113 mL, and an AUA Symptom Index score of 7.7.
      Complications included urinary tract infection in two, urethral stricture in one,
      and bladder neck contracture in 3 men. Four men have subsequently elected
      additional treatment for bladder outlet obstruction (two transurethral
      resections, one repeat laser, and one terazosin), for an overall treatment
      failure rate of 6 of 67 (9%), including the two men who remain catheterized.
      Laser coagulation prostatectomy produces little or no acute morbidity with a
      successful long-term voiding outcome in the majority of men requiring treatment
      for acute or chronic urinary retention.

PMID- 9181453
TI  - Multichannel urethral pressure profiles: reproducibility and three-dimensional
      representation.
AB  - Urethral pressure profilometry (UPP) is used to investigate the pressure
      distribution in the urethra. Single UPP is dependent on the orientation of the
      catheter during the study. To circumvent this problem, we developed a system for
      multichannel profilometry (MCUPP) that can be used in daily clinical practice. In
      the study reported in this article, 29 healthy female volunteers (mean age 34.6
      years) underwent MCUPP. The mean time needed to make five pressure profiles
      ranged from 4 to 12 minutes (mean 7.6). The system is patient- and user-friendly.
      The volunteers scored the discomfort on a 1 to 10 scale, with 10 meaning no
      discomfort at all, rendering a mean score of 7.6. The Symmetry Index (SI) is a
      calculated variable expressing the asymmetry in the pressure profiles. An SI of 1
      means a completely symmetrical pattern of pressure distribution. The mean SI for
      the whole group was 0.7 (range 0.407-0.930). The standard deviation was 0.109.
      Within-subject SI was highly reproducible (Greenhouse-Geisser epsilon = 0.98292).

PMID- 9181454
TI  - Reversal of tumor-induced immunosuppression: a new approach to cancer therapy.
AB  - Many studies show defective immune responses in patients diagnosed with cancer.
      Most of the diverse nonspecific approaches used to stimulate the immune system to
      recognize and destroy abnormal tumor cells have limited clinical utility.
      Attempts to identify tumor-specific antigens and to improve the antigen
      presentation were equally disappointing. It appears that some of these failures
      can be explained by tumor-induced immunosuppression. A large number of cytokines,
      hormones, and other molecules secreted by tumors were demonstrated to have
      immunomodulating properties. The most extensively studied immunosuppressive
      molecules secreted by tumors are transforming growth factor-beta (TGF beta),
      interleukin 10 (IL-10), and prostaglandin E2 (PGE2). TGF beta in particular may
      play a key role in tumor-induced immunosuppression. It is the most potent
      immunosuppressor described to date, and it has been consistently isolated from
      variety of tumor cell lines and detected in plasma of tumor-bearing hosts. Level
      of TGF beta production by tumor cells correlates with their metastatic potential,
      and TGF beta neutralization not only prevents development of metastases, but also
      inhibits growth or completely eradicates tumors as diverse as breast cancer,
      melanoma, and malignant gliosarcoma in animal models. PGE2 may play significant
      role in early stages of tumor development, promoting the process of tumorigenesis
      in some tumors. Research on reversal of tumor-induced immunosuppression promises
      new, more powerful, and less toxic approaches to cancer therapy. Existence of
      molecule(s) consistently secreted by different types of tumors and responsible
      for tumor progression raises the possibility of a single, universal assay to
      monitor progression and recurrence in many malignancies, including those that
      currently do not have reliable plasma markers.

PMID- 9181455
TI  - The multiple ways to tumor tolerance.

PMID- 9181456
TI  - Delivery of cytokines by liposomes. III. Liposome-encapsulated GM-CSF and TNF
      alpha show improved pharmacokinetics and biological activity and reduced toxicity
      in mice.
AB  - In an attempt to potentiate the therapeutic index of cytokines, recombinant mouse
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and recombinant human
      tumor necrosis factor alpha (TNF-alpha) were encapsulated in large (0.3-2.2
      microns) multilamellar vesicles composed of various lipids, using several
      encapsulation methods. Liposomal cytokine activity was tested in vitro and in
      vivo and was compared with that of the soluble cytokines. The main observations
      were as follows: (a) The mean encapsulation efficiency, as determined by
      bioassays, was 49-79%, depending on the formulation, for GM-CSF, and 48% for TNF
      alpha; (b) some of the entrapped cytokine preparations displayed high stability
      at 4 degrees C, with < 30% loss of biologic activity during a 4-month period; (c)
      release of TNF-alpha, but not of GM-CSF, from the liposomes was required for
      their biological activity in vitro; (d) plasma half-lives (t1/2 alpha, t1/2 beta)
      and the area under the curve (AUC) of the entrapped cytokines were 10-20 times
      greater than those of the soluble cytokines; (e) the toxicity of liposomal TNF
      alpha was one-third and one-seventh that of soluble TNF-alpha in normal and tumor
      bearing mice, respectively; (f) administration of liposomal GM-CSF (5 x 10(4)-2 x
      10(5) U, one to five times) to normal and 5-fluorouracil-treated mice led to a
      two- to fourfold increase in the absolute number of peritoneal and spleen
      leukocytes and of GM colony-forming cells in the spleen, as compared with the
      levels obtained using soluble GM-CSF; and (g) under the experimental conditions
      used, neither free nor liposomal GM-CSF significantly increased the absolute
      number of blood leukocytes, although liposomal GM-CSF markedly (threefold)
      enhanced the level of blood granulocytes. Collectively, these findings suggest
      that liposome-entrapped GM-CSF and TNF-alpha may be more efficacious
      immunomodulators than the soluble cytokines.

PMID- 9181457
TI  - Improved antibody targeting with interferon-alpha-2b conjugate.
AB  - This investigation is based on a hypothesis that a biological response modifier,
      interferon-alpha-2b (IFN), when conjugated with a specific monoclonal antibody
      (mAb) and given to tumor-bearing animals before the administration of
      radiolabeled mAb, may not only augment the tumor uptake but may also impede the
      liver and blood uptake, because the mAb associated with the conjugate may block
      nonspecific hepatic binding sites and scavenge circulating antigens. ME 31.3 and
      anti-carcinoembryonic antigen (CEA) F-6 (IgG-2a) specific for human melanoma and
      colorectal carcinoma, respectively, were chosen as prototype mAbs and conjugated
      with IFN-alpha-2b for evaluation in athymic nude mice bearing respective
      experimental tumors. The mAb specificity for the tumor cell line was examined by
      binding assays and Kd values were determined to be 1.96 x 10(-9) M and 5.9 x 10(
      9) M for ME 31.3 and anti-CEA F-6, respectively. Thirty micrograms of conjugate,
      prepared chemically and purified chromatographically (IFN-mAb:1:1), was
      administered intravenously to each animal and 3 h later followed by an
      intravenous injection of 20 micrograms F(ab')2 of corresponding mAb labeled with
      300 muCi Tc-99m (1.5 Ci/mmol). Twenty-four hours later, in melanoma-bearing
      animals, not only did the tumor uptake increase, but also the liver uptake
      decreased by 75%. Tumor/muscle and tumor/blood ratios also enhanced by 200 and
      500%, respectively. Consistent with ME 31.3, the tumor uptake with anti-CEA F-6
      also increased (p = 0.00) and the liver uptake decreased (p = 0.01). Similarly,
      tumor/muscle (p = 0.01) and tumor/blood (p = 0.02) ratios also increased
      significantly. Results indicate that IFN:mAb conjugate may improve diagnostic and
      therapeutic potential of mAbs, and is worthy of further studies.

PMID- 9181458
TI  - Effects of hyperthermic isolated limb perfusion with tumor necrosis factor-alpha
      and melphalan on pulmonary function assessments.
AB  - High doses of tumor necrosis factor-alpha (TNF) seem to be effective in the
      treatment of solid tumors in the extremities. By applying current intensive care
      technology, systemic administration of high doses of TNF levels might be feasible
      for the treatment of cancer in other localizations. To establish the early and
      late effects of high systemic TNF levels on the lungs, we determined lung
      function parameters in 12 patients before and after hyperthermic isolated limb
      perfusion (HILP) with TNF and melphalan. Because of leakage during perfusion,
      mean maximum systemic TNF levels of 60.0 ng/ml (range, 0.3-356 ng/ml) were
      obtained. Significant alterations in the vital capacity (VC), the capillary blood
      volume (Vc), the diffusing capacity of the alveolocapillary membrane (Dm), and
      the transfer capacity of the lungs for carbon monoxide per unit alveolar volume
      (KCO) were observed 1 week after HILP. Eight weeks after HILP, they returned to
      pretreatment value. Alterations in lung functions were not related to the maximum
      systemic TNF level. In conclusion, disturbances in pulmonary functions are
      observed in patients after HILP with TNF and melphalan. These disturbances, which
      are probably partly caused by high systemic TNF levels, are reversible and would
      not preclude administration of systemic TNF in high doses.

PMID- 9181460
TI  - Points to consider in the manufacture and testing of monoclonal antibody products
      for human use (1997). U.S. Food and Drug Administration Center for Biologics
      Evaluation and Research.

PMID- 9181459
TI  - Adjuvant immunotherapy in malignant melanoma: impact of antibody formation
      against interferon-alpha on immunoparameters in vivo.
AB  - In an adjuvant clinical trial for high-risk patients with malignant melanoma by
      using recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha 2b (rIFN
      alpha 2b), we monitored the development of antibodies against rIFN-alpha and
      various immunoparameters as biologic markers for IFN activity in vivo. Thirty-one
      patients (22 men, nine women) with high-risk malignant melanoma received eight 6
      week cycles of rIL-2 and rIFN-alpha. Serum samples of all patients were screened
      for the presence of antibodies against IFN-alpha by a solid enzyme immunoassay
      (EIA). Specimens testing positive in the EIA were assessed for their ability to
      neutralize the antiviral effects of IFN-alpha in vitro in an antibody
      neutralizing bioassay (ANB). Furthermore, serum levels of neopterin, beta 2
      microglobulin, soluble IL-2 receptor (sIL-2R), anticardiolipin and
      antithyroglobulin were evaluated. Of 31 patients, 11 (36%) developed binding
      antibodies; three (27%) of them had antibodies with neutralizing capacities
      (range, 350-28,000 INU/ml). Of male patients, 8 (36%) of 22 versus 1 (11%) of
      nine female patients developed antibodies. Statistical analysis (unpaired t test)
      revealed that all patients with antibody titers showed significant (p < 0.04)
      lower serum levels of beta 2-microglobulin and reproducible decreases in sIL-2R
      levels, whereby those with neutralizing antibodies showed significantly (p <
      0.0001) lower values than did those with binding antibodies. Elevations of
      anticardiolipin (17 of 31) and antithyroglobulin (one of 31) were not correlated
      to the presence of IFN antibodies. Our results show the in vivo significance of
      antibodies against rIFN-alpha, especially of those with neutralizing capacities.
      Monitoring of antibody formation as well as immunoparameters like beta 2
      microglobulin in clinical trials can contribute to identifying patients who, if
      necessary, might benefit from alternative IFN treatment, for instance, by using
      natural IFNs.

PMID- 9181461
TI  - Hypertriglyceridemia during long-term interferon-alpha therapy in a series of
      hematologic patients.
AB  - Adverse reactions to interferon-alpha (IFN-alpha) therapy include flu-like
      syndrome, bone marrow suppression, neurotoxic effects, and autoimmunity. A slight
      increase in triglyceride levels has been described less frequently during IFN
      alpha administration. The incidence of IFN-alpha-induced hypertriglyceridemia
      seems variable, and there are no clear data on how to treat it. We report the
      effect of long-term (more than 12 months) IFN-alpha treatment on triglyceride
      levels in 43 patients suffering from hairy cell leukemia (18), multiple myeloma
      (10), chronic myelogenous leukemia (6), cryoglobulinemia (5), non-Hodgkin's
      lymphoma (3), and Sezary syndrome (1). Hypertriglyceridemia was found in 6
      patients (15%). In 3 patients, gemfibrozil restored normal triglyceride values.
      This study suggests that hypertriglyceridemia is a minor side effect of long-term
      IFN-alpha therapy and that gemfibrozil might be considered the treatment of
      choice.

PMID- 9181462
TI  - Chemotherapeutic purine analogs alter the level of interferon-beta mRNA induced
      by poly I-poly C in cultured osteosarcoma cells.
AB  - The purine nucleoside analogs fludarabine, 2-chlorodeoxyadenosine, and 2'
      deoxycoformycin exhibit impressive activity in lymphoproliferative malignancies
      of adults and children. Their mechanism of action is not clear. Studies have
      suggested that their use is associated with significant myelosuppression,
      immunosuppression, and in some circumstances, increased infection with viral and
      opportunistic pathogens. Because interferons (IFNs) are known to have
      immunomodulatory activity as well as potent antiproliferative and antiviral
      activity, we examined whether the chemotherapeutic purine nucleoside analogs
      alter interferon-beta (IFN-B) gene expression in MG63 in human osteosarcoma
      cells. Northern blot analysis showed a dose-dependent inhibition of IFN-B mRNA
      accumulation in response to a known inducer (Poly I-Poly C) all three purine
      analogs. Hybridization analysis also revealed that inhibition of IFN-beta mRNA
      accumulation by the purine analogs is not a result of decreased mRNA stability.
      Further analysis of gene expression by PCR differential display indicated that
      the effect of the purine analogs was restricted to only a limited number of
      inducible genes. The data suggest that these molecules alter the signaling
      process involved in regulating the expression of specific genes, including IFN
      beta. These findings predict that the use of purine nucleoside analogs may reduce
      IFN production in vivo and thereby abrogate host defenses against infectious
      pathogens.

PMID- 9181463
TI  - In vivo expression of an interferon-alpha gene by intramuscular injection of
      naked DNA.
AB  - Acid-stable type I interferons belong to a multigene family. The biologic
      relevance of each subtype in vivo remains unknown. We have developed an
      experimental model in which muscles were transfected in situ with naked DNA
      plasmids encoding an IFN transgene to assess the roles of individual IFN subtypes
      in vivo. Murine IFN-alpha 9 gene was subcloned into several mammalian expression
      vectors. Adult C57BL/6 mice were injected bilaterally in regenerating tibialis
      anterior muscles with naked DNA 5 days after muscle injury to enhance DNA uptake
      and expression. In the muscles of mice given the IFN-alpha 9 plasmid constructs,
      acid-stable IFNs were detected by bioassay using reduction in cytopathic effect
      of encephalomyocarditis virus-infected L929 cells. In these same muscles, IFN
      alpha 9 transcripts were identified by RT-PCR, indicating that transcription had
      occurred. Acid-stable IFNs were detected from days 7 to 28 post-DNA inoculation.
      Furthermore, these proteins were found in the sera of DNA-inoculated mice.
      Control groups of mice given the blank expression vectors did not produce
      detectable IFNs in muscle or sera as determined by bioassay, nor were transcripts
      detected by RT-PCR. This approach now allows investigation of the effector
      function of individual subtypes in various murine disease models.

PMID- 9181464
TI  - Interferons suppress mitochondrial gene transcription by depleting mitochondrial
      transcription factor A (mtTFA).
AB  - Mitochondrial gene transcription activity in organello was suppressed after
      culturing HeLa cells with 1000 U/ml of interferon-alpha (IFN-alpha) or IFN-gamma
      for 18 h. The suppression was associated with reduced levels of mitochondrial
      gene transcripts. Northern blot analysis of HeLa cell RNA showed marked reduction
      of the mRNA encoding for mitochondrial transcription factor A (mtTFA).
      Immunoblotting with antiserum directed against recombinant mtTFA showed a reduced
      level of the protein as well. Consistently, gel-retardation assay of
      mitochondrial extract showed reduced level of functional mtTFA, which is known to
      bind to both heavy and light strand promoters of bidirectionally transcribed
      mitochondrial DNA. We suggest that depletion of mtTFA is a pathway through which
      IFNs depress the mitochondrial respiration.

PMID- 9181465
TI  - Dietary fish oil enhances circulating interferon-gamma in mice during listeriosis
      without altering in vitro production of this cytokine.
AB  - The objective of this study was to investigate the impact of feeding mice a diet
      rich in n-3 polyunsaturated fatty acids (PUFA) from fish oil on the interferon
      gamma (IFN-gamma) response during an active infection with Listeria
      monocytogenes. Weanling female C3H/Hen mice were fed experimental diets
      containing 20% by weight one of the following fats: soybean oil, lard, or a
      mixture of menhaden fish oil and corn oil (17:3, w/w). After 4 weeks, mice were
      injected with 10(5) live L. monocytogenes, and the concentration of IFN-gamma in
      serum and spleen was determined 0, 2, 4, and 7 days postinfection by enzyme
      linked immunosorbent assay (ELISA). Fish oil-fed mice showed significantly higher
      IFN-gamma in their blood at 2 and 4 days postchallenge compared with mice fed the
      soybean oil-containing or lard-containing diets (p < 0.001). A higher
      concentration of IFN-gamma was also found in the spleen homogenate of fish oil
      fed mice on day 4 postchallenge (p < 0.005). To examine in vitro IFN-gamma
      production, splenocytes were isolated from fish oil-fed and soybean oil-fed mice
      on day 4 postchallenge and cultured with concanavalin A (1 microgram/ml and 10
      micrograms/ml) for 24 and 48 h. There were no significant differences in the IFN
      gamma concentration in cell culture supernatants between these diet treatments.
      This study demonstrated that the elevation in the concentration of IFN-gamma in
      blood and spleen during murine listeriosis is accentuated and prolonged by
      dietary n-3 PUFA, and these effects may not be due to changes in IFN-gamma
      production.

PMID- 9181467
TI  - Obstruction of HIV-1 particle release by interferon-alpha occurs before viral
      protease processing and is independent of envelope glycoprotein.
AB  - The effect of human interferon-alpha (Hu-IFN-alpha) on the maturation process of
      the human immunodeficiency virus type 1 (HIV-1) has been studied using stable
      cell lines that produce nonenveloped particles. These cell lines secrete
      particles devoid of the viral envelope proteins gp120 and gp41. The CH-1 cells
      produce active viral protease that correctly processes its natural substrates,
      whereas the CH-1kww cell line expresses an enzymatically inactive viral protease,
      thus producing immature viral capsids. A block in the secretion of particles was
      observed in both cell lines when treated with 100-1000 U/ml Hu-IFN-alpha, as
      judged by measurements of encapsidated gag proteins. Electron microscopy shows
      that Hu-IFN-alpha-treated CH-1 cells are decorated with assembled immature
      particles at the cell surface. These results suggest that the observed block in
      particle release on Hu-IFN-alpha treatment is independent of viral envelope
      expression and occurs before capsid polyprotein processing. In addition,
      particles remaining attached to the cell fail to mature into structures with
      condensed cores. Viral gag proteins from IFN-treated and untreated CH-1 cells
      were analyzed by 2-D gel electrophoresis. Results suggest a change in
      posttranslational modifications of gag proteins, as IFN treatment allowed the
      detection of more basic forms of p55, p39, and p24. Further analysis of cellular
      or viral protein alterations induced by Hu-IFN-alpha treatment may identify the
      mechanism of action by which particle maturation is obstructed.

PMID- 9181466
TI  - Identification of genes induced by interleukin-3 and erythropoietin via the Jak
      Stat5 pathway using enhanced differential display-reverse southern.
AB  - Cytokines mediate their effects on growth and maturation of hematopoietic cells
      by binding to their cognate receptors and activating target genes. Interleukin-3
      (IL-3) and erythropoietin (Epo) induce signal transduction via the Jak-Stat
      pathway. We report here on the identification of several known and novel genes
      induced by IL-3 and Epo, using a modified version of the PCR-based technique,
      enhanced differential display (EDD). We modified the technique to facilitate the
      screening and verification of the differential expression of the genes by using
      reverse Southern blotting (RS) and PCR-Southern blotting, and we called it EDD
      RS. From the initial 110 genetags that were identified as differential expressed
      genes, 14 contained more than one gene. Among the differentially expressed genes,
      24 are known genes and 39 are novel genes. Several of the known genes, such as
      IRF-1 and P21waf, were previously observed by others to be induced by IL-3 and
      Epo, but their dependence on Stat5 activation in cytokine-dependent cells was
      unknown. Other known genes, such as crp and Mssp2/1, were not described
      previously as target genes for cytokine induction. The results demonstrate that
      EDD-RS is an efficient method to identify cytokine-induced genes and can be
      productive in delineating the signal required for their induction.

PMID- 9181468
TI  - Two forms of NF-kappa B1 (p105/p50) in murine macrophages: differential
      regulation by lipopolysaccharide, interleukin-2, and interferon-gamma.
AB  - In macrophages, nuclear factor kappa B (NF-kappa B) has been shown to
      transactivate the promoters of many cytokines, including tumor necrosis factor
      alpha (TNF-alpha). We have used the -510 kappa B binding site from the murine TNF
      alpha promoter to assay the induction of NF-kappa B in murine macrophages by
      various stimuli. A basal level of NF-kappa B activity in murine macrophages was
      detectable, and this activity was enhanced by treatment of these cells with
      lipopolysaccharide (LPS) or interleukin-2 (IL-2). Interferon-gamma (IFN-gamma),
      an important regulator of macrophage gene expression, significantly enhanced NF
      kappa B activity and altered the apparent molecular weight of the NF-kappa B1
      like proteins in LPS-stimulated and IL-2-stimulated murine macrophages. The NRD
      (NF-kappa B/Rel/Dorsal) complexes induced by LPS and IFN-gamma were further
      characterized by addition of antisera to electrophoretic mobility shift assay
      (EMSA) reaction mixtures. NF-kappa B1/p50 was a component of all complexes,
      whereas RelA/p65 was present in the IFN-gamma/LPS-stimulated activity. IFN-gamma
      priming or treatment with LPS for 19 h resulted in an upregulation of the larger
      species of NF-kappa B1/p50. In addition, regulation of the two pools of NF-kappa
      B1/p50 by IFN-gamma was confirmed by Western immunoblot analysis of cytosolic and
      nuclear extracts. This is the first demonstration of the presence of two pools of
      NF-kappa B1/p50 differentially regulated in response to cytokine activation of
      macrophages.

PMID- 9181470
TI  - Nomenclature of interferon receptors and interferon-delta.

PMID- 9181469
TI  - Costimulation with ultraviolet B and interleukin-1 alpha dramatically increase
      tumor necrosis factor-alpha production in human dermal fibroblasts.
AB  - Ultraviolet light, particularly in wavelengths of 290-320 nm (UVB), is known to
      induce cytokine synthesis in the skin. Cytokines act in a cascade fashion and can
      have synergistic or antagonistic actions on regulation of other cytokines. In
      this study, we sought to determine whether cotreatment with UVB and interleukin-1
      alpha (IL-1 alpha) induces tumor necrosis factor-alpha (TNF-alpha) production
      synergistically by human dermal fibroblasts. UVB irradiation (200 J/m2) or IL-1
      alpha (10 ng/ml) independently induced small amount of TNF-alpha (< 25 pg/ml)
      from human dermal fibroblasts. However, combined treatments with UBV and IL-1
      alpha induced 30-40-fold higher levels of TNF-alpha (750 pg/ml) than with either
      UVB of IL-1 alpha treatment alone. This synergy was also seen with mRNA
      expression. Maximum synergistic effect was observed when IL-1 alpha was added
      immediately after irradiation. Considering the fact that UVB is capable of
      causing release of IL-1 alpha from human keratinocytes and approximately 10% of
      incident UVB penetrates to the level of dermal fibroblasts, our results suggest
      that UVB may act in a cascade fashion to induce inflammation by initial release
      of keratinocyte IL-1 alpha, which then synergizes with UVB on human dermal
      fibroblasts to significantly increase TNF-alpha production.

PMID- 9181471
TI  - Bad genes, good people, association, linkage, and the environment.

PMID- 9181472
TI  - The SWISS-PROT protein sequence database: its relevance to human molecular
      medical research.

PMID- 9181473
TI  - STAT6: its role in interleukin 4-mediated biological functions.
AB  - Interleukin (IL) 4 is known to be a cytokine which plays a central role in the
      regulation of immune response. Studies on cytokine signal transduction have
      clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic
      proteins, signal transducer and activator of transcription (STAT) 6 and IL4
      induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are
      activated in IL4 signal transduction. Recent studies from STAT6-deficient mice
      have revealed the essential role of STAT6 in IL4-mediated biological actions. In
      addition, STAT6 has also been demonstrated to be important for the functions
      mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce
      the production of IgE, which is a major mediator in an allergic response. These
      findings indicate that STAT6 activation is involved in IL4- and IL13-mediated
      disorders such as allergy.

PMID- 9181474
TI  - The beta cell transcription factors and development of the pancreas.
AB  - The pancreatic beta cell is the major source of circulating insulin in adult
      mammals. In the multistep process of insulin synthesis it is initiation of
      transcription that restricts insulin synthesis to the beta cell since all
      subsequent steps can be performed by other cell types. Many of the transcription
      factors that bind to the insulin promoter and activate insulin gene transcription
      have been isolated. Some of these factors are restricted in their expression
      pattern, but so far no truly beta cell-specific transcriptional activator has
      been found. Since different transcription factors synergize to activate insulin
      gene transcription, cell-specific transcription of insulin is probably realized
      through the interactions of a unique set of regulatory proteins in the beta cell.
      The same transcription factors that regulate insulin gene transcription in the
      adult beta cell are involved in determining cell differentiation during
      pancreatic development. The endocrine and exocrine pancreas form from the gut
      endoderm as a dorsal and a ventral bud which later fuse to build a single organ.
      The homeodomain protein PDX-1, an insulin gene transcription factor, is uniformly
      expressed in the early pancreatic bud, and null mutation of PDX-1 in mice results
      in a failure of the pancreatic bud to grow and differentiate. Other transcription
      factors, such as the helix-loop-helix protein Beta-2 and the homeodomain protein
      Nkx 6.1, show a restricted pattern of expression during embryogenesis and in the
      mature islet. Those proteins may serve a dual role for the organism: during
      embryogenesis they may determine islet cell differentiation and in the adult they
      may ensure tissue-specific expression of the islet cell hormones. A better
      understanding of the factors involved in insulin gene transcription and islet
      cell differentiation will ultimately provide the basis for novel therapy of
      diabetes.

PMID- 9181475
TI  - Clinical implications of the involvement of tPA in neuronal cell death.
AB  - Tissue plasminogen activator (tPA), the serine protease that converts inactive
      plasminogen to the protease plasmin, was recently shown to mediate
      neurodegeneration in the mouse hippocampus. Mice deficient in tissue plasminogen
      activator (tPA) display a dramatic resistance to a paradigm of excitotoxic
      neuronal death that involves intrahippocampal injection of the excitotoxin. This
      model is thought to reproduce the mechanism of neuronal death observed during
      acute (such as ischemic stroke) and degenerative (such as amyotrophic lateral
      sclerosis) diseases of the nervous system. The requirement for the proteolytic
      activity of tPA to mediate neuronal death is acute in the adult mouse. Serine
      protease inhibitors, specific for tPA or the tPA/plasmin proteolytic cascade, are
      effective in conferring extensive neuroprotection following the excitotoxic
      injection. These findings suggest possible new ways for interfering with the
      neuronal death observed in the hippocampus as a result of excitotoxicity. In
      addition, tPA is produced in the hippocampus primarily by microglial cells, which
      become activated in response to the neuronal injury. Blocking microglial
      activation has been shown in other injury paradigms to protect against neuronal
      death, therefore suggesting another way to retard neurodegeneration in the CNS.
      Furthermore, after the insult has been inflicted and in the presence of a
      compromised blood-brain barrier macrophages (cells deriving from the same lineage
      as microglia) migrate into the brain, where they are thought to contribute to the
      neuronal cell loss by secreting neurotoxic molecules. If these
      macrophages/microglia expressed, however, a tPA inhibitor, rather than the
      possibly neurotoxic tPA, they might be able to protect the neurons from dying.

PMID- 9181476
TI  - Interferon regulatory factors: growth control and histone gene regulation--it's
      not just interferon anymore.
AB  - Interferon-regulatory factors (IRFs) are a related family of proteins originally
      identified by their ability to bind a DNA sequence found in the beta-interferon
      gene and many interferon-stimulated genes. Two well-studied members of this
      family, IRF-1 and IRF-2, have antagonistic roles in interferon-beta gene
      regulation: IRF-1 activates this gene, and IRF-2 represses the activation by IRF
      1, IRF-1 and IRF-2 have more recently been linked to growth control by displaying
      tumor suppressor and oncogenic activities, respectively. A possible explanation
      for the oncogenic activity of IRF-2 is the discovery that IRF-2 can activate a
      histone gene that is functionally coupled to cell cycle progression. This first
      report of native IRF-2 playing the role of activator of a gene essential for
      growth may lead to the discovery of a more general involvement of interferon
      regulatory factors in mediating growth control.

PMID- 9181477
TI  - Antibacterial vaccines: impact of antigen handling and immune response.
AB  - The emerging awareness that diseases caused by bacterial pathogens cannot be
      vanquished by chemotherapy alone has recalled interest in the generation of novel
      vaccines. Vaccines have proven their efficacy for the bacterial pathogens that
      are controlled by antibodies. In contrast, satisfactory vaccines are not
      available for intracellular bacteria that are under the control of T lymphocytes.
      This review describes the T cell populations that must be activated by successful
      vaccines against intracellular bacteria and discusses parameters that need to be
      fulfilled by protective T cell antigens. These parameters include: (a) the
      intracellular localization of the pathogen with major effect on antigen
      presentation and stimulation of distinct T cell subsets and (b) the antigen
      display which markedly influences kinetics of T cell activation. Using
      tuberculosis as an example, the advantages and disadvantages of second-generation
      vaccine candidates are discussed.

PMID- 9181478
TI  - Are Canadian Inuit at increased genetic risk for coronary heart disease?
AB  - The Keewatin Inuit of the Northwest Territories of Canada have a very low age
      adjusted mortality rate from coronary heart disease. We hypothesized that this
      apparent protection from disease has a genetic basis. We determined the
      prevalence of the disease-associated alleles of five candidate genes for
      atherosclerosis-related phenotypes. Surprisingly, four of the five alleles
      studied, namely AGT T235, FABP2 T54, PON R192 and APOE E4, were significantly
      more frequent in a sample of 175 Keewatin Inuit than among a representative
      control sample of whites living in the region. The high frequencies of these
      disease-associated alleles suggests either that they have no relationship with
      disease susceptibility in the Inuit, or that some unmeasured genetic and/or
      environmental factors mitigate disease susceptibility that is associated with
      these alleles. This highlights the difficulty in extrapolating findings from one
      population to another. Also, very modest genotype-phenotype associations were
      observed between APOE genotype (P = 0.016) and plasma low-density lipoprotein
      cholesterol concentration and between FABP2 genotype and plasma 2-h postprandial,
      glucose concentration (P = 0.048). The relationship between APOE alleles and
      plasma low-density lipoprotein cholesterol was the same as has been previously
      reported in many study samples. However, the relationship between FABP2 alleles
      and plasma 2-h postprandial glucose concentrations was the opposite to that
      reported in other studies. This suggests that differences in environment, such as
      the type of fatty acid consumed, interacts with functional differences in gene
      products involved in candidate metabolic pathways to produce phenotypic
      differences.

PMID- 9181479
TI  - Cardiovascular end-organ damage in Ren-2 transgenic rats compared to
      spontaneously hypertensive rats.
AB  - To compare hypertensive end-organ damage in two genetic forms of hypertension we
      assessed cardiovascular function in two rat strains of genetic hypertension:
      transgenic rats overexpressing the mouse Ren-2 gene [(TGR(mREN2)27]) and blood
      pressure matched spontaneously hypertensive rats (SHR). Despite similarly
      elevated blood pressure, systolic dp/dt (mmHg/s) was more impaired in transgenic
      rats (3099 +/- 446) than in SHR (3571 +/- 272) and normals (4342 +/- 119; P <
      0.05). Left ventricular weight (mg/g body weight) increased more in the
      transgenic rats (40 +/- 3) than in SHR (31 +/- 2) and normals (26 +/- 2).
      Endothelium-dependent relaxation was significantly decreased only in the
      transgenic rats. This study shows significantly more cardiac and endothelial
      dysfunction in transgenic, hypertensive TGR (mREN2)27 than in age and blood
      pressure matched SHR. This supports the hypothesis that chronic activation of the
      renin-angiotensin system significantly contributes to hypertensive end-organ
      damage.

PMID- 9181480
TI  - Molecular abnormalities of human plasminogen isolated from synovial fluid of
      rheumatoid arthritis patients.
AB  - Plasminogen (Pg) in the synovial fluid of patients with acute inflammatory
      disease, including rheumatoid arthritis, osteoarthritis, and gout, was purified
      by affinity chromatography techniques. The Pg isolated from patients with
      osteoarthritis and gout has affinities for L-lysine Sepharose and structural
      properties similar to those of normal plasma Pg. However, Pg from rheumatoid
      synovial fluids is abnormal in that it does not bind to L-lysine Sepharose.
      Analyses of rheumatoid synovial fluid Pg purified by immunoaffinity
      chromatography indicate that the molecule has size and folding properties similar
      to those of normal plasma Pg. However, we detected abnormalities in the molecule
      using two different criteria. First, isolated kringles 1-3 fragments are unable
      to bind L-lysine Sepharose. Second, reactivity toward a monoclonal antibody
      against a region in kringles 1-3 is decreased. In addition, rheumatoid synovial
      fluid Pg competes with normal plasma Pg for binding to the receptor on rheumatoid
      synovial fibroblasts but not on normal synovial fibroblasts. We also found that
      binding and activation of rheumatoid synovial fluid derived Pg on the surface of
      rheumatoid synovial fibroblasts elicits a rise in the concentration of cytosolic
      free Ca2+ similar to that of normal plasma Pg. Our data suggest that the
      inability of rheumatoid synovial fluid Pg to bind to L-lysine Sepharose is due to
      minor structural changes in kringle 1-3. These changes do not affect the
      physiological properties or the binding ability of synovial fluid Pg to cellular
      receptors on cells obtained from rheumatoid synovial tissue.

PMID- 9181481
TI  - A Schwann cell matrix component of neuromuscular junctions and peripheral nerves.
AB  - Molecules localized to the synapse are potential contributors to processes unique
      to this specialized region, such as synapse formation and maintenance and
      synaptic transmission. We used an immunohistochemical strategy to uncover such
      molecules by generating antibodies that selectively stain synaptic regions and
      then using the antibodies to analyse their antigens. In this study, we utilized a
      monoclonal antibody, mAb 6D7, to identify and characterize an antigen
      concentrated at frog neuromuscular junctions and in peripheral nerves. In adult
      muscle, immunoelectron microscopy indicates that the antigen is located in the
      extracellular matrix around perisynaptic Schwann cell at the neuromuscular
      junction and in association with myelinated and nonmyelinated axons in peripheral
      nerves. The maintenance of the mAb 6D7 epitope is innervation-dependent but is
      muscle-independent; it disappears from the synaptic region within 2 weeks after
      denervation, but persists after muscle damage when the nerve is left intact. mAb
      6D7 immunolabelling is also detected at the neuromuscular junction in developing
      tadpoles. Biochemical analyses of nerve extracts indicate that mAb 6D7 recognizes
      a glycoprotein of 127 kDa with both N- and O-linked carbohydrate moieties. Taken
      together, the results suggest that the antigen recognized by mAb 6D7 may be a
      novel component of the synaptic extracellular matrix overlying the terminal
      Schwann cell. The innervation-sensitivity of the epitope at the neuromuscular
      junction suggests a function in the interactions between nerves and Schwann
      cells.

PMID- 9181482
TI  - PK ('peripheral benzodiazepine')--binding sites in the CNS indicate early and
      discrete brain lesions: microautoradiographic detection of [3H]PK11195 binding to
      activated microglia.
AB  - The isoquinoline PK11195 has been suggested as a marker of glial pathology in the
      lesioned brain. The aim of the present study is to clarify the precise cellular
      location of its binding site in the central nervous system. Here, we report that
      in the facial nucleus after facial nerve axotomy-a lesion causing a retrograde
      neuronal reaction without nerve cell death while keeping the blood-brain barrier
      intact--activated microglia are the predominant source of lesion-induced
      increases of PK11195 binding. Likewise, increased PK11195 binding is seen in the
      gracile nucleus after anterograde neuronal injury following sciatic nerve
      transection. The peak of PK11195 binding, using the single isomer R-PK11195, was
      observed 4 days after the peripheral nerve lesion, consistent with the well-known
      time course of microglial activation. Photoemulsion microautoradiography
      confirmed the restriction of PK11195 binding to activated microglia. The increase
      of PK11195 binding in the facial nucleus seen after selective cell death of
      facial motoneurons by retrograde suicide transport of toxic ricin, a lesion that
      is accompanied by the rapid transformation of microglia into phagocytes, was no
      higher than that seen following axotomy. This suggests that the full
      transformation of microglia into parenchymal phagocytes is not necessary to reach
      maximal levels of PK11195 binding. PK11195, therefore, is a well-suited marker to
      detect microglial activation in areas of subtle brain pathology, where neither a
      disturbance of the blood-brain barrier function nor the presence of macrophages
      and inflammatory cells indicate an on-going disease process.

PMID- 9181483
TI  - Glial organization and chondroitin sulfate proteoglycan expression in the
      developing thalamus.
AB  - This study examines the early organization of glial cells, together with the
      expression of chondroitin sulfate proteoglycans in the developing thalamus of
      ferrets. Glia were identified with antibodies against vimentin and glial
      fibrillary acidic protein and the chondroitin sulfate proteoglycans were
      identified by using an antibody against chondroitin sulfate side chains. Our
      results reveal three striking features of early thalamic development. First,
      there is a distinct population of glial fibrillary acidic protein-immunoreactive
      astrocytes (first seen at E30) that resides in the perireticular thalamic nucleus
      of the primordial internal capsule. These glial fibrillary acidic protein
      immunoreactive astrocytes of the perireticular nucleus are transient and form a
      conspicuous feature of the early developing forebrain. They are first apparent
      well before any glial fibrillary acidic protein-immunoreactive astrocytes are
      seen in other regions of the thalamus (at about P8). Further, unlike in other
      thalamic regions, these peculiar perireticular astrocytes do not express vimentin
      before they express glial fibrillary acidic protein. Second, in the reticular
      thalamic nucleus, the radial glial cells express glial fibrillary acidic protein;
      they are the only ones to do so in the thalamus during development. The glial
      fibrillary acidic protein-immunoreactive radial glial cells of the reticular
      nucleus form a rather distinct band across the developing thalamus at these early
      stages (E30-P1). Finally, and preceding the expression of glial fibrillary acidic
      protein, the radial glial cells of the reticular nucleus, unlike those in other
      thalamic regions, are associated closely with the expression of chondroitin
      sulfate proteoglycans (E20-E30). Later (after E30), the expression of the
      chondroitin sulfate proteoglycans in the reticular nucleus declines sharply. The
      significance of this finding is related to the early organization of the cortico
      fugal and cortico-petal pathways.

PMID- 9181484
TI  - Monosialoganglioside (GM1) immunofluorescence in rat spinal roots studied with a
      monoclonal antibody.
AB  - Gangliosides are characteristic glycolipid components of plasma cell membranes,
      especially enriched in the CNS and PNS. In some diseases involving the PNS, in
      particular motor neuropathies associated with conduction block, IgM
      autoantibodies against ganglioside GM1 have been implicated as a pathogenic
      factor. In order to study the GM1 distribution in peripheral nerves we have
      investigated its in situ localization using a new anti-GM1 monoclonal antibody,
      GM1:1. Immunization and production of the monoclonal antibody was made by common
      protocols and binding specificity was investigated by using structurally related
      glycolipids and modified GM1-molecules. The result showed that an alpha 2-3 bound
      sialic acid together with a terminal galactose moiety were essential for GM1:1
      binding. In situ localization of GM1 in rat dorsal and ventral spinal roots was
      investigated by conventional immunomicroscopy. GM1 immunoreactivity was the same
      in both roots and appeared like a finely granular, in places confluent, material
      confined to Schmidt-Lanterman's incisures, to myelin sheath paranodal end
      segments and to some extent to the abaxonal Schwann cell cytoplasm; all of these
      structures are likely to be the target for GM1 antibodies in peripheral
      neuropathies. Nodal gaps and fibre contours showed a weak non-specific
      fluorescence. The localization of GM1 to the incisures of Schmidt-Lanterman and
      the paranodal end segments of the myelin sheaths might indicate a role of
      gangliosides as adhesion molecules.

PMID- 9181485
TI  - Cellular distribution of myosin-V in the guinea pig cochlea.
AB  - The importance of unconventional myosins to hearing has recently been revealed by
      the identification of myosins-VI and -VII as the defective genes in mouse
      mutations and in a human syndrome which lead to profound hearing loss. Another
      class of novel myosins (V) has been implicated in the trafficking of
      intracellular vesicles in neurons and other secretory cells. We used affinity
      purified antibodies to determine the localization of myosin-V in the guinea pig
      inner ear. In the sensory epithelium of the cochlea, myosin-V epitopes were
      recognized in neuronal and supporting cells. Neuronal labelling was most intense
      in the afferent innervation of inner and outer hair cells. Supporting cells
      labelled were cells of Hensen and Deiters, and inner border, inner phalangeal,
      inner sulcus and interdental cells. In the vascular tissue of the cochlea, we
      observed staining of intermediate cells of the stria vascularis and of border
      cells between the stria and the spiral prominence. Staining of afferent chalice
      nerve endings was observed on type I vestibular hair cells. The results suggest
      that, like myosins VI and VII, myosin-V is localized in positions that may be
      critical to auditory function.

PMID- 9181486
TI  - Neuronal activation of the hypothalamic magnocellular system in response to
      oropharyngeal stimuli in the rat.
AB  - The present study was designed to delineate the neuronal site, the nature, and
      the gastrointestinal origin of the stimulation of the hypothalamic magnocellular
      system induced by the ingestion of sweetened condensed milk. Concomitant
      localization of the c-fos protein (Fos) with either arginine-vasopressin (AVP)
      mRNA or oxytocin (OT) mRNA in the paraventricular nucleus of the hypothalamus
      (PVH) and the supraoptic nucleus (SON) revealed that the hypothalamic neurons
      containing AVP and OT were activated following ingestion of sweetened condensed
      milk. Expression of c-fos mRNA was also determined in rats implanted with a
      gastric cannula that allowed for real, sham, and gastric feeding of sweetened
      condensed milk. The results provide evidence that the stimulation of the PVH and
      SON induced by sweetened condensed milk originate from oropharyngeal stimuli.
      Indeed, in real-and sham-fed rats, the postprandial levels of c-fos mRNA in the
      PVH and SON were significantly higher than the preprandial values, whereas there
      was no early postprandial rise in c-fos mRNA levels within the magnocellular
      division of the PVH and SON after gastric feeding. The results of this study also
      suggested that the stimulation of the PVH and SON induced by sweetened condensed
      milk was related to the hypertonicity of the milk, indeed, ingestion of an
      hypertonic solution of sucrose with a carbohydrate content close to that of
      sweetened condensed milk led to a stimulation of the PVH and SON that was
      comparable to that induced by the milk, whereas ingestion of an isotonic solution
      of sucrose did not trigger any significant activation of the PVH and SON. Taken
      together, the present results indicate that magnocellular neurosecretory neurons
      are sensitive to oropharyngeal stimuli and further support the view of the
      existence of oropharyngeal osmoreceptors.

PMID- 9181487
TI  - Anterior pituitary release of prolactin is inhibited by exposure to short
      photoperiod.
AB  - The potential regulatory sites responsible for the decrease of circulating
      prolactin (PRL) levels shown by many photoperiodic mammals following prolonged
      exposure to short days was investigated in Siberian hamsters that had been
      maintained under a stimulatory, long-day photoperiod, and in hamsters that had
      been shifted to a nonstimulatory, short-day photoperiod for 8-10 weeks. The
      ability of anterior pituitary fragments (AP) from each of these groups to release
      prolactin was evaluated in pituitary tissue cultured alone and also in pituitary
      tissue co-cultured with hypothalamic fragments (HF), using a perifusion tissue
      culture system. The perfusate from these cultures was collected every 1/2 h for 8
      h, and was assayed for basal levels of prolactin using radioimmunoassay. For AP
      tissue cultured alone, there was a robust reduction in prolactin release by the
      fragments harvested from short-day housed animals. In AP tissue harvested from
      long-day exposed animals, co-culture with either long- or short-day HF did not
      induce significant changes in basal PRL release. Similarly, co-culture with short
      day HF did not significantly alter PRL release in short-day APs. However, there
      was a significant increase in release when short-day APs were co-cultured with
      long-day HF. These results suggest a direct effect of photoperiod on PRL
      synthesis and/or release at the level of the pituitary. However, the altered
      responsiveness of short-day pituitaries could be the result of previous, chronic
      inhibitory hypothalamic input during short-day exposure. A follow-up study was
      conducted to investigate the ability of vasoactive intestinal peptide (VIP) to
      stimulate PRL release from long- and short-day APs. Results indicated that the
      ability of VIP to stimulate PRL release is both photoperiod and dose dependent.

PMID- 9181488
TI  - Electrophysiological evidence for retinal projections to the hypothalamic
      supraoptic nucleus and its perinuclear zone.
AB  - Secretion of vasopressin (VP) and oxytocin (OT) displays a daily rhythm. Using
      electrophysiological methods, we investigated the projections from the optic
      nerve to the supraoptic nucleus (SON) and its perinuclear zone (PNZ) which might
      underlie the rhythm. Extracellular recordings were made from magnocellular cells
      in the SON and its PNZ in 22 urethane-anaesthetized female Wistar rats while
      stimulating the optic nerve. The responses of magnocellular and PNZ cells were
      classified as orthodromic excitatory (OD+) or inhibitory (OD-) after creating
      peri-stimulus time histograms (PSTHs). Twenty-six of 73 (35.6%) VP and OT cells
      and 16 of 42 (38.1%) PNZ cells were excited by optic nerve stimulation. PNZ cells
      displayed both short (for 7 cells 30 ms or less) and long (> 60 ms) latency
      responses. Most (6/7) short latency responses had a short duration but longer
      latency responses were longer. No magnocellular cells showed responses with both
      short latency and short duration. Short latency responses with a short duration
      probably reflect direct monosynaptic inputs whereas longer latency responses with
      longer duration may reflect complex inputs. Thus the retina projects to the PNZ
      and to the SON but the PNZ receives a stronger direct input. Such projections
      might provide a light-related input to SON cells and suggest a role for the PNZ
      in this input.

PMID- 9181489
TI  - Long-term adrenalectomy can decrease or increase hippocampal dentate gyrus
      volumes.
AB  - Male and female Long-Evans adult rats were adrenalectomized and sacrificed 6
      weeks later to determine whether dentate gyrus damage would differ in females and
      males. A subset of adrenalectomized rats of both sexes had significantly reduced
      dentate gyrus volumes compared to the same sex SHAM operated rats. The remainder
      of the male and female adrenalectomized rats which did not have clear dentate
      gyrus damage had significantly larger dentate gyrus volumes compared to the same
      sex SHAM rats. The dentate gyrus volumes of all adrenalectomized rats were
      significantly correlated with two indices of residual hormonal levels (Na+/K+
      ratios and body weight gain 6 weeks after surgery), indicating that endogenous
      corticosterone levels may be a determining factor in the response of the dentate
      gyrus to adrenalectomy. These dentate gyrus volumetric changes could not be
      attributed to tissue shrinkage as there were no changes in CA3 volumes in any of
      the groups. These results suggest that long-term adrenalectomy can result in
      either increased or decreased dentate gyrus volumes and that the adrenal steroid
      levels of each individual adrenalectomized rat may be the factor determining the
      direction of the dentate gyrus volumetric response.

PMID- 9181491
TI  - Projection sites of medial preoptic area and ventral bed nucleus of the stria
      terminalis neurons that express Fos during maternal behavior in female rats.
AB  - Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis
      (VBST) neurons are involved in maternal behavior, but the neural sites to which
      the maternally relevant neurons project have not been determined. Since MPOA and
      VBST neurons express Fos during maternal behavior, we used a double-labeling
      immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat
      germ agglutinin (WGA), in order to determine where these Fos neurons project. On
      Day 4 postpartum, fully maternal females were separated from their litters. On
      Day 5, WGA was iontophoretically injected into one of the following regions known
      to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the
      level of the ventromedial nucleus, lateral habenula, ventral tegmental area,
      retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test
      with either pups or candy, after which they were perfused and their brains were
      processed for the detection of Fos and WGA. As expected, females tested with pups
      had more Fos-containing neurons in the MPOA and VBST than did females tested with
      candy. After WGA injections into several brain sites, the number of double
      labeled cells observed in the MPOA and VBST was greater for the maternal females
      when compared to the non-maternal females. Therefore, these results pinpointed
      neural circuits that were activated during maternal behavior. For the maternal
      females, Fos-containing neurons in the MPOA projected most strongly to the medial
      hypothalamus at the level of the ventromedial nucleus and to the lateral septum,
      while Fos-containing neurons in the VBST projected most strongly to the
      retrorubral field, ventral tegmental area, and medial hypothalamus. Although
      relatively few MPOA and VBST neurons which expressed Fos during maternal behavior
      projected to the periaqueductal gray, these Fos-expressing neurons made up a
      relatively large proportion of the MPOA and VBST projection to the periaqueductal
      gray. This study suggests that MPOA and VBST efferents project to a variety of
      regions to promote full maternal responsiveness.

PMID- 9181490
TI  - Reduced aggressive behaviour in mice with targeted disruption of the oxytocin
      gene.
AB  - Oxytocin (OT) has been reported to mediate aggressive and affiliative behaviours
      in several species. The behavioural role of OT has been established with
      physiological manipulations that potentially affected blood pressure, which may
      have indirectly affected the behaviours under study. To provide converging
      evidence of the physiological role of OT in aggressive behavior, wild type (WT),
      heterozygous (OT-/+), and homozygous (OT-/-) mutant mice were tested in two
      aggression paradigms. In general, there was no significant difference in
      aggressiveness between WT and OT-/+ mice. However, there were significant
      reductions in the duration of aggressive behaviors among OT-/- animals,
      especially in agonistic encounters within neutral arenas. The OT-/- mice did not
      exhibit any sensorimotor deficits or display any altered general anxiety levels
      that may have accounted for the observed reduction in aggressive behavior. These
      data indicate that aggression is mediated in part by OT in mice and that
      increased aggressiveness is not an obligatory phenotypic result of targeted
      genetic disruption of any gene.

PMID- 9181492
TI  - D1 dopamine receptor agonist (SKF-38393) induction of Fos immunoreactivity in
      progestin receptor-containing areas of female rat brain.
AB  - Injection of dopamine or dopamine receptor subtype agonists facilitates the
      expression of lordosis in estrogen-primed female rats. The D1 receptor specific
      agonist, SKF-38393, facilitates lordosis in estradiol-primed female rats via a
      process that requires progestin receptors. Based on these data, neuronal response
      to the D1 receptor agonist SKF-38393 was assessed by expression of the immediate
      early gene protein, Fos. In the first experiment we examined the modulation of
      Fos expression by D1 agonists in progestin receptor-containing areas of estradiol
      primed female rat brain. In the second experiment we examined if there are
      progestin if there are progestin receptor-containing cells that respond to
      stimulation of D1 receptors with increased Fos expression. Ten to 14 days
      following ovariectomy and stereotaxic surgery, animals were injected with 5
      micrograms estradiol benzoate. Forty eight h later they were injected
      intracerebroventricularly with 100 ng of SKF-38393 or saline. One h following
      injection animals were perfused, and brain sections immunostained for Fos
      protein. Results from the first experiment suggest that SKF-38393 increased the
      total number of Fos immunoreactive cells in the mid-ventromedial hypothalamic
      nucleus/ventrolateral portion (VMHVL), the caudal VMHVL, the paraventricular
      hypothalamic nucleus and the caudate putamen. In the medial preoptic area, the
      rostral VMHVL and the arcuate hypothalamic nucleus, there was a significant
      increase in the number of darkly stained Fos-immunoreactive cells following the
      SKF-38393 treatment. In the second study, SKF-38393 increased the number of
      progestin receptor-containing cells which contained Fos immunoreactivity in the
      caudal VMHVL. The results suggest potential sites of action for the facilitation
      of sexual behavior by centrally administered D1 agonists.

PMID- 9181493
TI  - Gender-specific induction of pituitary RNA by estrogen and its modification by
      thyroid hormone.
AB  - Estrogen and thyroid hormones play important roles in the regulation of pituitary
      function. We presently show that pituitary weight and total cellular RNA levels
      were significantly decreased by ovariectomy in female rats and were significantly
      increased by castration in males, without alterations in pituitary DNA levels as
      compared to intact animals. Treatment with a single dose of estrogen produced a
      significant increase in pituitary RNA in ovariectomized females but not castrated
      males. This effect was more obvious following multiple doses of estrogen, and was
      blocked by pretreatment with cycloheximide, or surprisingly by concomitant
      administration of triiodothyronine (T3). Analysis of estrogen response element
      (ERE) binding activity in pituitary nuclear protein extracts revealed that
      estrogen produced a rapid induction of a slow mobility complex of ERE binding in
      ovariectomized females much greater than in castrated males. Thus, estrogen
      induced increases in pituitary total RNA levels are dependent on new protein
      synthesis, are gender-specific, are inhibited by T3, and may be mediated via
      specific estrogen-induced changes in protein-DNA interactions.

PMID- 9181494
TI  - Gunshot wounds: a public health care crisis.

PMID- 9181495
TI  - The impact of gunshot wounds on an orthopaedic surgical service in an urban
      trauma center.
AB  - OBJECTIVE: To determine the prevalence of gunshot wound related orthopaedic
      injuries in an urban trauma center and outline the socioeconomic background of
      this patient population. DESIGN: Retrospective study conducted from January 1,
      1994, through December 30, 1994. SETTING: University-affiliated level 1 trauma
      center. PATIENTS: Strict inclusion and exclusion criteria were established.
      INCLUSION CRITERIA: All patients were admitted through the emergency room with a
      gunshot wound for which the orthopaedic surgery service was consulted. The study
      group consisted of 284 patients. EXCLUSION CRITERIA: Those individuals excluded
      from the study were patients with an orthopaedic injury who died during or before
      attempts at resuscitation in the emergency room and patients treated on an
      outpatient basis. MAIN OUTCOME MEASURES: Orthopaedic and nonorthopaedic
      diagnoses, etiology, procedures performed, number of hours from admission to the
      first surgical procedure, average daily hospital census, drug and alcohol screen
      results, and patient financial status. RESULTS: The orthopaedic service was
      consulted on 284 patients admitted with gunshot wounds. This group comprised 24%
      of all orthopaedic admissions, 33% of the average daily orthopaedic census, and
      14% of all orthopaedic surgery cases performed. Ninety-four percent were African
      American and 87% were male, with a mean age of 27 years. Approximately half were
      tested for alcohol and/or drugs, 45% of whom were positive for alcohol and 65%
      for drugs. Only 4% of the patients were privately insured. CONCLUSIONS: During
      the period of this study, gunshot wound injuries required more orthopaedic trauma
      resources than any other single diagnosis.

PMID- 9181496
TI  - Biomechanical, scanning electron microscopy, and microhardness analyses of the
      bone-pin interface in hydroxyapatite coated versus uncoated pins.
AB  - OBJECTIVE: To evaluate the bone-pin interface in hydroxyapatite coated versus
      uncoated pins. DESIGN: Eighty-four bicylindrical stainless steel external
      fixation pins were implanted in a test group of 14 sheep. One-half of the pins
      were coated with hydroxyapatite and the rest remained uncoated. INTERVENTION: Six
      coated pins were implanted in the left tibia of seven sheep, and six uncoated
      pins were implanted in the left tibia of the other seven sheep. In all sheep, the
      right tibia was left intact. During pin implantation, the final insertion torque
      was measured, and a linear external fixator was mounted on the pins. Then the
      medial tibial mid-diaphysis was exposed and a 5-mm resection osteotomy was
      performed. The sheep were killed six weeks after surgery. MAIN OUTCOME MEASURES:
      The extraction torque was measured on four pins removed from each sheep.
      Radiographic pin tract rarefaction was measured on all the pins. Two pins from
      each sheep were used for histologic, scanning electron microscopy (SEM), and
      microhardness analysis. Histomorphometric analysis was carried out on the SEM
      specimens at x 36 magnification. RESULTS: Radiographic pin tract rarefaction was
      significantly lower in the hydroxyapatite coated pins than in the uncoated pins
      (P < 0.001). Group average insertion torque was 960 +/- 959 N/mm in the
      hydroxyapatite coated pins, and 709 +/- 585 N/mm in the uncoated pins (p = not
      significant). Group average extraction torque was 1485 +/- 1308 N/mm and 298 +/-
      373 N/mm, respectively (p = 0.0001). Histomorphometric analysis showed that the
      group average bone-pin contact was 50.7 +/- 16.9% in the hydroxyapatite coated
      pins and 27.6 +/- 7.1% in the uncoated pins (p < 0.01). Microhardness analysis
      showed that bone tissue close to the pins was softer than bone tissue far from
      them. CONCLUSION: Hydroxyapatite coating is an effective method of refining the
      bone-pin interface and may improve the clinical results of the external fixation
      technique.

PMID- 9181497
TI  - Hip fractures in the elderly: predictors of one year mortality.
AB  - OBJECTIVE: To determine the one year mortality following hip fracture in an
      ambulatory, community dwelling, cognitively intact elderly population and to
      examine the role of specific type, number, and severity of associated medical
      comorbidities. DESIGN: Prospective, consecutive. METHODS: Six hundred twelve
      elderly who sustained a non-pathologic hip fracture were followed. RESULTS:
      Twenty-four patients (4%) died during hospitalization; seventy-eight (12.7%) died
      within one year of fracture. The factors that were predictive of mortality, based
      on multivariate analysis, were patient age > 85 years, preinjury dependency in
      basic activities of daily living, a history of malignancy other than skin cancer,
      American Society of Anesthesiologists rating of operative risk 3 or 4, and the
      development of one or more in-hospital postoperative complications; all factors
      other than the development of an in-hospital complication were independent of
      treatment. CONCLUSION: These results indicate that efforts at reducing one year
      mortality after hip fracture should be directed at the prevention of
      postoperative complications.

PMID- 9181498
TI  - Total hip arthroplasty for complications of proximal femoral fractures.
AB  - OBJECTIVES: To determine problems associated with and to present the results of
      secondary total hip replacement for complications of proximal femoral fractures.
      SETTING: An acute care hospital with a prospectively entered database for primary
      total hip arthroplasty. PATIENTS AND PARTICIPANTS: The prospective database was
      reviewed to extract all patients undergoing primary total hip replacement for
      complications of treatment of proximal femoral fractures. These fifty-three
      patients were then compared with fifty-three patients from the same data bank
      matched for age, sex, weight, prosthesis type, and length of follow-up but who
      had not sustained a proximal femoral fracture before total hip replacement.
      INTERVENTION: Primary total hip arthroplasty for complications of proximal
      femoral fractures. After the surgical procedure, patients were seen at follow-up
      intervals of three months and six months and, thereafter, yearly. MAIN OUTCOME
      MEASUREMENTS: Patients were evaluated using the St. Michael's hip rating scale,
      which is a scale measuring pain, motion, and function specifically designed for
      evaluation of total hip arthroplasty. Routine radiographs were obtained at each
      patient visit. RESULTS: The complications associated with total hip replacement
      in patients with previous proximal femoral fracture fixation occurred more
      frequently than in patients who had not had undergone previous fracture fixation;
      in addition, intraoperative surgical difficulty was significantly greater in
      those patients who had undergone previous surgery for hip fracture. However, the
      final hip score at > or = 2 years after total hip arthroplasty was not
      statistically different between the two patient groups. CONCLUSION: Total hip
      replacement is a satisfactory salvage procedure for failed fracture treatment
      despite the increased incidence of operative difficulty and increased incidence
      of complication.

PMID- 9181499
TI  - Results of an operative policy in the treatment of periprosthetic femoral
      fracture.
AB  - OBJECTIVE: To determine the clinical outcome of patients with periprosthetic
      femoral fractures treated operatively. DESIGN: Retrospective analysis from 1986
      to 1993. SETTING: Edinburgh Orthopaedic Trauma Unit, Edinburgh, Scotland.
      PATIENTS: Forty-five patients identified from a computer database as being
      admitted to the Edinburgh Orthopaedic Trauma Unit with periprosthetic femoral
      fractures. MAIN OUTCOME MEASURES: Clinical outcome grade (good, fair, poor)
      dependent on integrity of fixation, refracture rate, and ability to perform
      activities of daily living analyzed against age, type of fracture, prosthetic
      alignment, loosening, and method of fixation. RESULTS: Type I fractures were more
      common in uncemented or loosely cemented prostheses, whereas type II fractures
      occurred predominantly in securely cemented prostheses. Type I fractures treated
      by revision had the poorest results. Outcome in type II fractures was equally
      good whether treated by internal fixation or by revision. Age, loosening, and
      prosthetic alignment did not influence outcome. The mortality rate in this series
      was 20%. CONCLUSIONS: If a prosthesis is loose, it should be revised, or
      treatment varies with fracture and prosthetic type. In type I fractures, an
      uncemented stem may be revised to a cemented one; however, a securely cemented
      prosthesis probably is better when fixed internally. Type II fractures should be
      fixed internally because there is less operative insult. Type III fractures
      probably are not related to the prosthesis and should be fixed internally
      according to normal practice. The results of an operative policy compare well
      with the results of conservative management and avoid the problems of long-term
      immobilization.

PMID- 9181500
TI  - Use of the Medoff sliding plate for subtrochanteric hip fractures.
AB  - OBJECTIVE: To evaluate the effects of dynamization of a sliding hip screw plate
      on the fixation stability for several types of subtrochanteric fractures.
      Clinical results of treating reverse oblique fractures occasionally show
      medialization of the femoral shaft. DESIGN: Two types of plate dynamization were
      compared using the same test protocol in identically prepared groups of uniform,
      artificial femurs. METHODS: Sawbones composite femurs (Pacific Research Labs,
      Vashon, WA) having five orientations of simulated subtrochanteric fractures were
      used with the Medoff plate (Medpac, Inc., Valencia, CA) either fully dynamized or
      with the sliding lag screw locked. These specimens were physiologically loaded
      and cycled and displacements of the proximal femur determined. RESULTS:
      Significantly more shaft medialization occurred with reverse oblique fracture
      patterns when the Medoff plate was fully dynamized. CONCLUSION: Clinical
      treatment of reverse oblique fractures with the Medoff plate should be performed
      using the lag screw locked and only the plate dynamized.

PMID- 9181501
TI  - Early complications in the operative treatment of patella fractures.
AB  - OBJECTIVE: To identify and review early complications in the operative treatment
      of patella fractures. DESIGN: Retrospective review. SETTING: Single tertiary care
      institution with multiple surgeons, including generalists and fellowship trained
      subspecialists. PATIENTS: A consecutive series of eighty-seven patella fractures
      over a five year period was reviewed. Patients treated nonoperatively or with
      partial or total patellectomy were excluded. Minimum follow-up to fracture
      healing (four months) was available in fifty-one fractures. INTERVENTION:
      Modified tension band wire fixation was used in forty-nine fractures, whereas two
      fractures were treated with tension band wires threaded through cannulated
      screws. OUTCOME MEASURES: Early complications such as loss of reduction or
      fixation, infection, or soft-tissue problems were evaluated. RESULTS:
      Displacement of > or = 2 mm before healing was noted in eleven fractures. The
      displacement could be attributed to technical errors in five cases, and to
      patient noncompliance with postoperative activity restrictions in another five
      cases. Two cases of superficial infection were documented. Nine patients with
      symptomatic hardware required hardware removal. CONCLUSIONS: Twenty-two percent
      of fractures treated with tension band wiring and early motion displaced > or = 2
      mm within the early postoperative period. Technical errors or patient
      noncompliance were identified as factors. The incidence of early complications in
      operatively treated patella fractures is higher than previously reported.

PMID- 9181502
TI  - Treatment of delayed and nonunion of the patella.
AB  - OBJECTIVE: To review our experience with nonoperative versus operative management
      of patients with patellar delayed union or nonunion. DESIGN: Retrospective study
      with an average follow-up of 64 months (range 5-135) after definitive treatment.
      SETTING: All patients were reviewed and evaluated at a large multi-specialty
      clinic. PATIENTS AND OTHER PARTICIPANTS: The series represents twenty patients
      who all presented to our institution with a diagnosis of patellar nonunion
      irrespective of their initial treatment. This included twelve males and eight
      females with an average age of 38 (range 12-76) years. Initial treatment of the
      original fracture was nonoperative in 12 and operative in eight. All fractures
      progressed to symptomatic nonunion at an average of 34 months from original
      injury (range 4-109). INTERVENTIONS: Definitive treatment of the nonunion was
      nonoperative in seven patients and operative in 13. Nonoperative management
      consisted of observation, activity modification, physical therapy, and local pain
      relief measures. Operative management included open reduction and internal
      fixation, partial patellectomy, or patellectomy. The internal fixation consisted
      of tension band wiring, Bunnell wiring, cerclage wiring, or screw fixation. MAIN
      OUTCOME OR MEASURES: Patients were reviewed for radiographic analysis as well as
      Knee Society knee and function scores. RESULTS: Definitive treatment was
      nonoperative in seven patients. Their mean Knee Society knee and function scores
      at the time of presentation with nonunion were 72 and 78, respectively, with an
      average knee range of motion of 127 degrees. The nonunions of thirteen patients
      were treated operatively. Knee Society knee and function scores at the time of
      presentation with nonunion averaged 82 and 80, respectively, with an average knee
      range of motion of 112 degrees. Patients who had operative management or elective
      nonoperative management performed better than those who refused operative
      management. Patients treated surgically had an average Knee Society score of 94,
      a function score of 93, and an average knee range of motion of 109 degrees. Those
      treated nonoperatively had an average knee score of 83, a function score of 75,
      and an average range of motion of 120.0 degrees. In the nonoperative group, all
      seven patients had persistent radiographic nonunion. Only one of thirteen
      patients treated operatively had persistent radiographic nonunion. CONCLUSION:
      Our findings suggest that patients with minimally symptomatic delayed union or
      nonunion of the patella can be successfully treated nonoperatively with the
      knowledge that the fracture will not unite. Operative management of symptomatic
      patients can be expected to achieve union and increase function of the knee.

PMID- 9181503
TI  - The infrapatellar branch of the saphenous nerve: an anatomic study.
AB  - OBJECTIVES: To describe the course of the infrapatellar branch of saphenous nerve
      (IPBSN) and define a risk zone in which the nerve would probably be located.
      DESIGN AND MATERIALS: The course of the IPBSN was studied in twenty-eight cadaver
      specimens (fifteen male and thirteen female) chosen haphazardly. SETTING AND MAIN
      OUTCOME MEASUREMENTS: The adductor tubercle and the junction between the inferior
      pole of the patella and the medial (point A) and lateral (point B) borders of the
      patellar tendon were taken as reference points. The level of the joint line as
      well as the point of crossing of the IPBSN at the joint line were measured in
      relation to point A. RESULTS: The IPBSN was located at 7.7 +/- 16.8 mm posterior
      to the adductor tubercle at the level of point A; at 0.8 +/- 20.5 mm anterior to
      the adductor tubercle at the level of joint line; and at 12.1 +/- 18.8 mm
      anterior to the adductor tubercle at 30 degrees from point A. The IPBSN crossed
      to the lateral border of the patellar tendon in 10 of the 28 specimens (36%). The
      vertical distance between point B and the nerve was 37.8 +/- 23.5 mm. Three zones
      are defined in relation to point A: a safe zone, a gray zone, and a risk zone.
      The limits of the safe zone could be represented by a curved line that crosses
      the following points: 31.0 mm medial to point A and at the same level; 17.2 mm
      from point A at the joint line; 13.2 mm infromedial to point A at an angle of 30
      degrees; 9.6 mm at an angle of 60 degrees; and 5.8 mm inferior to point A.
      CONCLUSION: Avoiding the risk zone in which the nerve would probably be located
      and performing a blind puncture or an arthrotomy within the safety zone may
      decrease the incidence of IPBSN injury.

PMID- 9181504
TI  - Intramedullary nailing of unstable diaphyseal fractures of the tibia with distal
      intraarticular involvement.
AB  - OBJECTIVE: To evaluate the efficacy of intramedullary nailing in diaphyseal tibia
      fractures with distal intraarticular involvement. DESIGN: Retrospective. SETTING:
      Henry Ford Hospital, a level I trauma center. PATIENTS/PARTICIPANTS: Twenty
      patients with twenty fractures at an average of twenty-two months of follow-up
      were evaluated. There were fifteen closed and five open fractures. INTERVENTION:
      All fractures were stabilized with lag screw fixation (with or without
      supplemental plates) of the intraarticular-fracture extension or ankle fracture,
      and intramedullary nailing of the diaphyseal tibia fracture. MAIN OUTCOME
      MEASUREMENTS: Time to bony union, malunion, knee and ankle range of motion, early
      arthrosis, and any complications of treatment were assessed. RESULTS: Nineteen
      fractures healed, with an average time to bony union of seventeen weeks. One
      nonunion after a grade IIIB open fracture required exchange nailing and healed
      after sixty-two weeks. Nineteen fractures had excellent alignment after healing.
      There were no infections. CONCLUSIONS: The indications for intramedullary nailing
      of unstable diaphyseal tibia fractures may be extended to include certain
      fractures with distal extension into the ankle joint, as well in a tibial shaft
      fracture occurring in combination with a noncontiguous ipsilateral ankle
      fracture.

PMID- 9181505
TI  - The role of fibular fixation in combined fractures of the tibia and fibula: a
      biomechanical investigation.
AB  - OBJECTIVES: To determine whether adjunctive plating of the fibula with tibial
      fixation enhanced the stability of the construct under combined compressive and
      bending loads in simulated fractures of both the tibia and fibula. METHODS: Each
      of twelve fresh cadaveric specimens (six pairs) with an intact knee, lower
      extremity, and foot was mounted on the table of a materials testing machine. An
      intramedullary (IM) rod locked in the distal femur allowed combined compression,
      and flexion, valgus bending, or varus bending loads to be transmitted from the
      actuator of the testing machine to the knee. Three displacement measurement
      transducers were mounted on the tibia at anterior, posterolateral, and
      posteromedial positions. Intact tibial deformations under load were measured.
      Then, in one specimen of each pair a 2 cm osteotomy was created near the tibial
      midshaft, which was stabilized with an external fixator. Tibial gap displacements
      were measured under the following conditions: (a) intact fibula, (b) osteotomized
      fibula, (c) fibula fixed with a plate, (d) fibula fixed with an Enders IM nail.
      In the other specimen of the pair, tibial fixation was performed with an
      interlocked unreamed IM nail, with the same successive stages of fibular
      fixation. RESULTS: Osteotomy of the fibula significantly increased tibial defect
      motion when external fixation was used, and plating the fibula in this case
      significantly decreased motion. Using an Enders rod to stabilize the fibula
      instead of a plate, with tibial external fixation, produced smaller decreases in
      tibial defect site motion. With IM rod fixation of the tibia, osteotomizing the
      fibula had no effect on defect site motion or on its subsequent stabilization
      using a plate or IM rod. CONCLUSION: Plating the fibula can decrease motion
      across a tibial defect, but only when less rigid (i.e., external) fixation is
      used.

PMID- 9181506
TI  - Plaster cast versus percutaneous pin fixation for comminuted fractures of the
      distal radius in patients between 46 and 65 years of age.
AB  - OBJECTIVE: To compare the results of treating unstable distal radius fractures
      either by percutaneous pinning and casting, or by traditional closed reduction
      and casting. DESIGN: Prospective, randomized. SETTING: University hospital.
      PATIENTS: Forty patients with unstable Frykmann III-VIII distal radius fractures
      resulting from a fall. INTERVENTIONS: Twenty patients were treated with closed
      reduction, consisting of manipulation, under local anesthesia, followed by
      casting. Twenty patients were treated with percutaneous fixation using K-wires,
      followed by casting. MAIN OUTCOME MEASUREMENTS: Initial displacement, quality of
      reduction, carpal malalignment, articular step-off. Range of motion and grip
      strength were measured using a scoring system reported by Home et al. (10).
      RESULTS: Functional results in the pinning group were better (excellent, 12;
      good, 6; fair, 2) than in the plaster group (excellent, 3; good, 8; fair, 5;
      poor, 4). Anatomic results also were better in the pinning group. CONCLUSION: The
      best anatomic and functional results were obtained by percutaneous pinning.
      Although the cost of pins and plaster treatment is significantly greater than
      plaster treatment, the author believes that the positive end result justifies the
      cost.

PMID- 9181507
TI  - A technique for intramedullary nailing of proximal third tibia fractures.
AB  - Twelve of 14 proximal third tibial shaft fractures were successfully treated with
      a new technique for intramedullary nailing of these fractures. The average
      anterior displacement was 3.0 mm (range 0-17). The average coronal plane
      alignment was 2.0 degrees valgus (range 2 degrees varus to 12 degrees valgus).
      There was one nonunion. The technique's success is dependent on neutralizing the
      primary factors causing malreduction: wide effective diameters of tibial nails,
      narrow diameter of the medial tibial metaphysis, and a posteriorly directed
      sagittal plane entrance angle.

PMID- 9181508
TI  - Intramedullary entrapment of the radial nerve associated with humeral shaft
      fracture.
AB  - We present an unusual case of a humeral shaft fracture with intramedullary
      entrapment of the radial nerve by an undisplaced posterior triangular fragment
      tightly fixed to the lateral intermuscular septum. Initial examination showed a
      complete high radial nerve palsy and an angulated mid-shaft humeral fracture
      associated with an undisplaced posterior triangular fragment. After failure of
      several closed reductions, we decided to attempt an open reduction and internal
      fixation with simultaneous exploration of the radial nerve. During surgery, the
      radial nerve was found emerging from the medullary canal of the proximal
      fragment. The nerve was freed by briefly displacing the undisplaced posterior
      triangular fragment. The fracture was then reduced and fixed by plate and screws.
      Six months after the operation, there was full recovery of the radial nerve and
      complete union of the fracture. Clearly, closed intramedullary nailing would be
      contraindicated in this particular type of associated radial nerve injury. We
      therefore suggest that in cases of mid-shaft fractures of the humerus with
      associated radial nerve palsy, and an undisplaced posterior triangular fragment,
      consideration should be given to the possible entrapment of the radial nerve in
      the medullary canal.

PMID- 9181509
TI  - Radial nerve palsy associated with slightly angulated pediatric supracondylar
      humerus fracture.
AB  - This report reviews a case of radial nerve palsy associated with a supracondylar
      fracture of the right humerus. The patient was a four-year-old boy. Radiographs
      of the injury showed simple extension and a slightly angulated fracture. Complete
      radial nerve palsy was observed at the first consultation. After three months of
      conservative treatment without any obvious improvement, an operative exploration
      of the right radial nerve was conducted. Intraoperatively, the nerve was found to
      be transected, with both ends of the ruptured nerve buried in scar tissue at the
      fracture site. Five months after the nerve suture operation, the palsy was cured
      completely. This case shows that even a minimal displacement fracture can be
      associated with severe nerve injury that requires surgical treatment.

PMID- 9181510
TI  - Scaphocapitate syndrome in a child associated with a distal radius and ulna
      fracture.
AB  - A case is presented of scaphocapitate fracture syndrome associated with a Salter
      Harris type II fracture of the distal radius and ulna occurring in an 11-year-old
      girl. The proximal fragment of the fractured capitate was rotated 180 degrees.
      The injury was treated by open reduction and internal fixation. One year after
      the injury, radiographs showed that fractures were united with no signs of
      avascular necrosis of the capitate. The patient had a full range of motion of the
      wrist, as well as full pronation and supination of the forearm. An awareness of
      this fracture entity is necessary to correctly diagnose this injury in a child.

PMID- 9181511
TI  - Fat embolism and death during prophylactic osteosynthesis of a metastatic femur
      using an unreamed femoral nail.
AB  - We report a case of cardiovascular collapse and death occurring intraoperatively
      during the prophylactic nailing of a metastatic femur using an unreamed femoral
      nail. The cause of death, as documented by the autopsy, was a massive fat
      embolism. The risk of fat embolism while performing intramedullary nailing is
      well known and has been linked to the process of medullary reaming. Unreamed
      femoral interlocking nails recently have become available. Although recent
      reports in the literature have concluded that the risk of fat embolism appears
      less likely while using unreamed implants, the surgeon should carefully consider
      the indications for any type of intramedullary fixation, particularly when
      dealing with unbroken femurs exhibiting impending pathologic fracture, or when
      preexisting pulmonary disease such as metastasis is present.

PMID- 9181512
TI  - Anterior subtalar dislocation: case report.
AB  - Anterior subtalar dislocations are extremely rare. To our knowledge, only four
      cases have been reported in detail in the literature. A diagnosis of anterior
      subtalar dislocation should be confirmed by an anteroposterior view radiograph
      because lateral subtalar dislocation always includes some anterior displacement
      of the mid-foot. We report a case of anterior subtalar dislocation confirmed by
      both lateral and anteroposterior view radiographs and discuss its pathomechanism,
      diagnosis, and treatment.

PMID- 9181513
TI  - Isolated case report of medical subtalar dislocation with associated posterior
      process of the talus fracture.

PMID- 9181514
TI  - Management of humeral nonunion after the failure of locking intramedullary nails.

PMID- 9181515
TI  - Titanium plate fixation.

PMID- 9181516
TI  - Prolonged exposure of chicks to light or darkness differentially affects the
      quinpirole-evoked suppression of serotonin N-acetyltransferase activity in chick
      retina: an impact on dopamine D4-like receptor.
AB  - Dopamine plays an important role in regulation of melatonin biosynthesis in
      retinas of several vertebrate species. In the avian retina, the dopamine receptor
      that controls melatonin production represents a D4-like subtype. Stimulation of
      this receptor by quinpirole (QNP) results in a dose-dependent decline of the
      nighttime activity of serotonin N-acetyltransferase (NAT, a key regulatory enzyme
      in melatonin biosynthesis) and melatonin level of the retina. The present study
      was undertaken to determine whether the ability of QNP to suppress nocturnal NAT
      activity of chick retina was affected by prolonged adaptation of animals to light
      and darkness. In the retina of chicks kept under a light:dark (LD) illumination
      cycle, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels measured at the
      end of the light phase were significantly higher than those found in the middle
      of the dark phase. In animals maintained under continuous light (LL) or darkness
      (DD) dopamine and DOPAC contents of the retina measured at these two time points
      were similar and resembled levels found during, respectively, the light and dark
      phase in the retina of chicks kept under LD illumination cycle. Adaptation of
      chicks to LL and DD resulted in an attenuated and enhanced, respectively,
      response of the retinal NAT activity to the suppressive action of QNP. When
      compared to the LD group, a parallel shift to the right (LL group) or left (DD
      group) of the dose-response curve for QNP was observed, and the ED50 values for
      this dopamine receptor agonist were 3.4-times higher (LL) or 2.8-lower (DD) than
      those calculated for the control LD animals. It is suggested that prolonged
      exposure to light or darkness, by altering the level of the retinal dopaminergic
      neurotransmission, may modify the reactivity of the D4-like dopamine receptors
      regulating NAT activity of the chick retina.

PMID- 9181517
TI  - Clarifying plasma melatonin profiles in domestic pigs: a critical and comparative
      evaluation of two radioimmunoassay systems.
AB  - The results of a direct radioimmunoassay (RIA) for porcine plasma melatonin,
      suggesting a relationship among plasma melatonin, feed intake and photoperiod,
      were investigated by comparison with the results of an extracted RIA. These
      findings were further examined by analysis of a small number of samples using gas
      chromatography-mass spectrometry (GCMS). The results identified inadequacies in
      the specificity of the direct RIA and failed to provide evidence for an effect of
      feed intake on melatonin secretion. Instead, it appeared that feed restriction
      exacerbated nonspecificity in the direct RIA. The cause of nonspecificity, and
      its effect on analysis of daily plasma melatonin profiles, were examined. The
      plasma component(s) responsible for nonspecificity was (were) not identified.
      However, the results suggest that characteristics of the antiserum used in the
      direct RIA are involved in the mechanism by which nonspecificity is induced.
      Results obtained using the extracted assay revealed that plasma melatonin
      concentrations in prepubertal gilts and pregnant sows exhibit a diurnal pattern,
      in which concentrations are low during daylight and modestly increased during
      darkness. Using the direct RIA, the same profiles exhibited highly variable
      melatonin concentrations showing little association with the light-dark cycle.
      Thus, assay specificity was identified as a factor contributing to
      inconsistencies in the literature describing plasma melatonin in the domestic pig
      and the importance of rigorous validation of RIAs was demonstrated. Furthermore,
      the results indicate that plasma melatonin concentrations in domestic pigs, as in
      other mammalian species, are entrained by the light-dark cycle.

PMID- 9181518
TI  - Effect of melatonin and corticosteroid on in vitro cellular immune function in
      humans.
AB  - It is well accepted that the immune system shows circadian rhythmicity and that
      circadian disruption can significantly alter indices of immune function.
      Recently, a functional link between the endocrine and immune systems has been
      proposed to explain circadian rhythms in immune activity. Of particular interest
      is the finding that hormones such as melatonin and corticosteroid are able to
      exert modulating effects on lymphocyte proliferation. Previous research examining
      the effects of melatonin in vitro, however, has produced equivocal results. The
      aim of this study, therefore, was to examine the effects of melatonin and
      corticosteroid, both separately and together, on mitogen-stimulated human
      lymphocyte proliferation. Purified human lymphocytes were stimulated with
      concanavalin A (Con A, 4 micrograms/mL). Melatonin and/or corticosteroid were
      added to the culture medium during incubation. All cultures were done in
      quadruplicate. As expected, corticosteroid (25-1,000 ng/mL) significantly reduced
      proliferation by between 30 and 60% in a dose-related manner (P < 0.0001).
      Melatonin alone (10-1,000 fmol/mL) did not significantly affect lymphocyte
      proliferation. However, when lymphocytes were cultured in the presence of
      melatonin and corticosteroid, a significant decrease in proliferative function of
      50-85% was observed (P < 0.0001). Hence, the effect of melatonin and
      corticosteroid combined was significantly greater than that observed with
      corticosteroid alone (P < 0.0001). Therefore, it appears that the in vitro effect
      of corticosteroid on immune function may be modulated by melatonin in
      physiological to pharmacological concentrations.

PMID- 9181519
TI  - Melatonin enhances cortisol levels in aged women: reversible by estrogens.
AB  - The administration of melatonin increases cortisol levels in postmenopausal
      women. Aging and hypoestrogenism are believed to impair the regulation of the
      hypothalamo-pituitary-adrenal axis and may participate in the determination of
      this altered response. In this study the implications of hypoestrogenism were
      tested. Seven postmenopausal women were studied. At 08.00 hr for 2 consecutive
      days, each woman received randomly and in a double blind fashion a pill of
      placebo or melatonin (100 mg). Serum melatonin and cortisol levels were evaluated
      at 20 min intervals, for 48 hr. Measurements were performed in the same subjects
      both during no estrogen supplementation and at least two cycles of conjugated
      estrogens administration (0.625 mg/day). During estrogen supplementation,
      postmenopausal women showed slightly lower cortisol levels at lunch and early
      night (20.00-01.00 hr). The onset of the nocturnal melatonin rise was not
      modified, but that of cortisol was delayed of about 60 min (P < 0.02). The
      administration of melatonin elicited a marked increase in daytime cortisol levels
      in postmenopausal women (P < 0.02), but this stimulus completely disappeared
      during estrogen administration. Mean nighttime (20.00-08.00 hr) cortisol levels
      were not modified by daytime administration of melatonin. The present data reveal
      that in aged postmenopausal women, reversal of hypoestrogenism, resulting from
      supplemental estrogens, may improve the regulation of the hypothalamopituitary
      adrenal axis.

PMID- 9181520
TI  - Effects of melatonin on mammary gland lesions in transgenic mice overexpressing N
      ras proto-oncogene.
AB  - The oncostatic effects of melatonin on the mammary gland have been studied in
      transgenic mice carrying the N-ras proto-oncogene under the control of the MMTV
      LTR. Female (4-week-old) virgin mice with positive transgenic pedigrees were
      injected with melatonin (200 micrograms/mouse/ day, five times a week) or vehicle
      late in the evening. After 5 months of treatment, animals were sacrificed and the
      mammary glands were dissected for whole mounts, histology, and
      immunohistochemical analysis with a mouse monoclonal antibody specific for N-ras
      protein. Mammary glands of control transgenic mice showed different densities of
      hyperplastic alveolar nodules (HANs) consisting primarily of dysplastic
      epithelial cells with nuclear atypia and prominent nucleoli. The epithelial cells
      of HANs showed a high expression of N-ras while no immunostaining was detected in
      the unaffected mammary parenchyma. Only one (10%) of the control transgenic mice
      presented an infiltrating ductal carcinoma with the neoplastic cells
      overexpressing N-ras protein. The mammary glands of melatonin treated mice had a
      lower density of HANs, absence of epithelial dysplastic cells, and weak
      immunostaining of N-ras protein in comparison to the vehicle-treated group. None
      of the melatonin treated animals developed mammary carcinomas during the
      observation period. The lymph nodes of the inguinal mammary glands of all the
      vehicle-treated transgenic mice presented hyperplasia and two animals even had
      lymphomas, whereas in melatonin-treated animals there was less hyperplasia (two
      cases were atrophic) and a lack of lymphomas. We conclude that in the mammary
      glands of MMTV-LTR/N-ras transgenic female virgin mice, melatonin a) reduces the
      incidence of HANs and the expression of N-ras protein in focal hyperplastic
      lesions, b) completely prevents the development of epithelial cell atypia and
      mammary adenocarcinomas, and c) also reduces the hyperplasia of the mammary
      lymphoid tissue and prevents the development of lymphomas.

PMID- 9181521
TI  - Pulsatile patterns of melatonin secretion in patients with gonadotropin-releasing
      hormone deficiency: effects of testosterone treatment.
AB  - Recently, we have demonstrated that male patients with gonadotropin-releasing
      hormone (GnRH) deficiency had increased nocturnal melatonin secretion that
      decreased to normal levels during testosterone treatment. The purpose of the
      current study was to examine if the abnormally increased melatonin levels in
      these patients were associated with pulsatile secretory patterns, and, if these
      were modified during testosterone administration. Characteristics of nocturnal
      melatonin and luteinizing hormone (LH) secretion were compared in six normal
      young males, six males with idiopathic hypogonadotropic hypogonadism (IGD), and
      in six males with constitutional delayed puberty (DP). Patients were examined in
      the untreated state and following the administration of 250 mg testosterone
      enanthate/month for 4 months. Serum samples for melatonin and LH levels were
      obtained every 15 min from 19.00 hr to 07.00 hr in a controlled light-dark
      environment. Pulse detection and pulse characteristics were determined by the
      program ULTRA. In comparison with normal controls, untreated IGD patients showed
      significantly higher pulse frequency, lower relative increments and shorter half
      life times for melatonin. Similar findings were observed in DP patients, although
      statistically of borderline significance. Treatment with testosterone normalized
      melatonin pulse characteristics in both IGD and DP patients. The secretory
      pattern of LH release in these patients was characterized by significantly higher
      relative and absolute increments and shorter half-life time without any
      significant change in the number of LH pulses. Taken together, these data suggest
      that melatonin is secreted in a pulsatile pattern in normal adult males and in
      male patients with GnRH deficiency. The abnormally increased nocturnal melatonin
      secretion observed in these patients may indicate that the pineal pulse generator
      is expressing an altered activity pattern within its normal capabilities.
      Testosterone administration normalized melatonin secretory patterns in IGD and DP
      patients. The lack of relationship between the pulsatile LH and melatonin
      secretory patterns suggest an independent signal for the nocturnal pulsatile
      melatonin and LH secretions.

PMID- 9181522
TI  - Melatonin production in an aerobic photosynthetic bacterium: an evolutionarily
      early association with darkness.
AB  - Melatonin was measured in a species of aerobic photosynthetic bacteria,
      Erythrobacter longus, grown in either constant light or constant dark. A
      radioimmunoassay was used to quantify melatonin levels and thin-layer
      chromatography to confirm the identity of melatonin immunoactivity. Melatonin
      levels were significantly higher (nearly 2.3-fold) in the dark-grown than in the
      light-grown samples. Also, the homogenates of the dark-grown bacteria retained
      melatonin-producing enzymatic activity, whereas the light-grown homogenates did
      not; melatonin levels extracted from the dark-grown homogenates increased with
      increasing extraction time, reaching as high as 29.2 ng.mg-1 protein at 120 min.
      Removal of membrane fragments from homogenates did not influence melatonin levels
      in light-grown homogenate, but this procedure increased melatonin levels in dark
      grown homogenate, indicating that at least some of the enzymes in the pathway of
      melatonin production are not membrane-bound. This study is the second to
      demonstrate the presence of melatonin at the prokaryotic level, supporting the
      evidence that melatonin appeared very early in evolution. Its function in
      prokaryotes has not been determined, but may relate to its antioxidative actions.

PMID- 9181523
TI  - Organ and species specificity of hepatitis B virus (HBV) infection: a review of
      literature with a special reference to preferential attachment of HBV to human
      hepatocytes.
AB  - Hepatitis B virus (HBV) infection is still a major public health problem
      worldwide. Although much information about the molecular biology of HBV has been
      gained in the last decades, little is known about the mechanism of attachment and
      penetration of the HBV particle into human hepatocytes. The HBV envelope proteins
      are important for the interaction between the HBV particle and the hepatocyte
      plasma membrane. Although initially it was suggested that the preS2 domain could
      act, via polymerized human serum albumin, as an attachment site to human
      hepatocytes, in recent years other observations showed that the preS1 domain is
      probably the most important attachment site to human hepatocytes. However,
      controversial findings on cellular proteins for binding to the preS1 domain has
      been described, namely the IgA-, the IL6-, the asialoglycoprotein receptor and
      GAPD. Although the preS1 attachment site may be important, apo H has been shown
      to bind specifically to small HBsAg. Recently, we have identified human liver
      Annexin V as a specific small HBsAg-binding protein. In a preliminary report, the
      direct involvement of human Annexin V in the initial step of HBV infection has
      been demonstrated. A rat hepatoma cell line, which does not express human Annexin
      V and which is not infectable by HBV, gained the ability to become infected by
      HBV after transfection with human Annexin V. This result may facilitate the
      progress of HBV receptor research and elucidate the molecular mechanism of the
      initial step of HBV infection.

PMID- 9181524
TI  - Epidemiology of hepatitis E virus infection.
AB  - Hepatitis E is an acute, icteric, self-limiting disease, which is spread widely
      in many tropical and subtropical countries where it occurs both in the form of
      epidemics of variable magnitude or sporadically. Hepatitis E affects young
      adults, rather than children, and causes a high mortality rate, particularly in
      pregnant women. In industrialized countries this disease occurs occasionally as
      imported sporadic cases. The aetiological cause of hepatitis E is a virus,
      hepatitis E virus (HEV), which is temporally classified as a member of the
      Calicivirus family, although its genomic composition is unique. There are
      experimental data as well as epidemiological observations allowing us to assume
      that hepatitis E may be a zoonosis as HEV is pathogenic for some domestic and
      wild animals. Recently, serological assays based on the use of recombinant or
      synthetic antigens were developed and applied to determine the prevalence of
      antibody to HEV (anti-HEV) in various epidemic and non-epidemic settings. In
      suspected hepatitis E cases, anti-HEV seropositivity was detected at an elevated
      rate but the overall seroprevalence of anti-HEV in normal human populations of
      endemic areas appeared to be unexpectedly low. A low but constant presence of
      anti-HEV seropositivity was observed also in non-endemic industrialized
      countries. In some of these countries, anti-HEV seropositivity was accumulated in
      groups of patients with various liver and non-liver pathologies and certain
      groups at risk for blood-borne infections.

PMID- 9181525
TI  - Inhibition of hepatitis B virus by retroviral vectors expressing antisense RNA.
AB  - Two retroviral vectors carrying an antisense gene from the hepatitis B virus
      (HBV) preS/S or preC/C were constructed and used to infect the human
      hepatoblastoma cell line 2.2.15, which expresses HBV surface antigen (HBsAg), HBV
      e antigen (HBeAg) and releases HBV particles. The results showed that the
      inhibitory effects of antisense gene transfer, mediated by retroviral vectors on
      the expression of HBV antigens, appeared as early as day 3 after transduction,
      reached a maximum on day 5 and persisted for at least 11 days. Our data indicate
      that, on day 5 after introduction, antisense preS/S inhibited HBsAg and HBeAg
      expression by 71% and 23%, and the antisense preC/C inhibited HBsAg and HBeAg
      expression by 23% and 59%. HBV DNA production, in the supernatant of the 2.2.15
      cells transduced with either antisense preS/S or preC/C, was also reduced on day
      5, but the viability of the 2.2.15 cells was not affected. Our results
      demonstrate that the replication and expression of HBV can be inhibited through
      antisense gene transfer mediated by retroviral vectors and that the antisense
      preC/C or antisense-preS/S may be potentially useful for clinical gene therapy
      against HBV.

PMID- 9181526
TI  - Predicted secondary structure of the hepatitis G virus and GB virus-A
      5'untranslated regions consistent with an internal ribosome entry site.
AB  - We describe comparative sequence analysis of 20 isolates of the recently
      discovered hepatitis G virus (HGV) and propose a model of the RNA secondary
      structure at the 3' end of the 5' untranslated region (UTR) of this virus. A
      single AUG starting at nucleotide position 552, which was in-frame and continuous
      with the putative polyprotein, was conserved in all 20 isolates and appeared to
      be the most likely site for the initiation of polyprotein synthesis. This
      consensus AUG was 14 amino acid residues upstream of a sequence with identity to
      the envelope protein E1 of hepatitis C virus (HCV), but the actual function of
      this N-terminal peptide of HGV is still not certain. None of the isolates encoded
      a sequence with similarity to the nucleocapsid protein of any known virus. The
      RNA secondary structure of the fragment under study was determined using
      thermodynamic modelling and validated using the results of comparative sequence
      analysis. Further support for the model was gained from the prediction of
      significant sequence and structural homology in the RNA secondary structure of
      the complete 5'-UTR of GB virus-A (GBV-A). A possible mechanism for translation
      initiation in HGV and GBV-A was suggested by the identification of features in
      common with the internal ribosome entry sites (IRESs) of HCV and picornaviruses.

PMID- 9181527
TI  - Ribavirin and interferon-alpha combination therapy vs interferon-alpha alone in
      the retreatment of chronic hepatitis C: a randomized clinical trial.
AB  - Interferon-alpha (IFN-alpha) induces sustained remission of chronic hepatitis C
      in approximately 25% of patients. In patients who are non-responders to the first
      course of therapy, retreatment with IFN-alpha is of limited efficacy. Ribavirin
      has also been used to treat chronic hepatitis C, but it induces only a transient
      response. In this study, we evaluated the efficacy of ribavirin and IFN-alpha
      combination therapy for IFN-alpha resistant chronic hepatitis C. Twenty-four IFN
      alpha non-responders and 24 relapsers were randomized to receive either ribavirin
      (1000 mg per day) together with IFN-alpha (3-6 million units (MU) thrice weekly)
      or the same dose of IFN-alpha alone, for 6 months. Both at the end of treatment
      and 6 months later, normal transaminase levels were more common in the patients
      receiving combination therapy than in the group receiving IFN-alpha alone: 17
      (70.8%) vs seven (29.2%) patients (P = 0.009) and six (25%) vs one (4.2%) patient
      (P = 0.034), respectively. At the end of treatment and 6 months later, serum HCV
      RNA was no longer detectable in eight (33.3%) and five (20.8%) patients in the
      combination therapy group and in six (25%) and one (4.2%) patient in the IFN
      alpha therapy group, respectively. Three patients (12.5%) were withdrawn
      prematurely from combination therapy because of side-effects; ribavirin therapy
      was ceased or dosage reduced in six other patients (25%), again because of side
      effects. In conclusion, this combination treatment was more effective than
      retreatment with IFN-alpha, alone, in inducing sustained biochemical remission of
      chronic hepatitis C that was resistant to a previous course of IFN-alpha. The
      combination treatment, however, was frequently associated with significant side
      effects.

PMID- 9181528
TI  - A model to predict long-term sustained response to interferon therapy in chronic
      hepatitis C.
AB  - Interferon therapy is used widely for chronic hepatitis C but only a minority of
      treated patients achieve a long-lasting sustained response. We have developed, by
      logistic regression, a mathematical model to estimate the probability of
      sustained response in an individual patient with chronic hepatitis C when treated
      with interferon-alpha (IFN-alpha). The model, which includes age, sex, disease
      duration, pretreatment serum gamma-glutamyl-transpeptidase, alanine
      aminotransferase and virus genotype, was developed from a database of 307
      patients and validated in a new set of 200 patients. It performed well as
      goodness-of-fit (P = 0.71 and P = 0.15 in the development and test sample,
      respectively) and discrimination (area under receiver operating curve = 0.79 in
      the development and 0.78 in the test sample, respectively). This model may
      provide decision support in the treatment of chronic hepatitis C with IFN-alpha.

PMID- 9181529
TI  - Age and platelet count: a simple index for predicting the presence of
      histological lesions in patients with antibodies to hepatitis C virus. METAVIR
      and CLINIVIR Cooperative Study Groups.
AB  - The aim of this study was to identify clinical and biological factors associated
      with histological lesions in patients with chronic hepatitis C and to construct a
      simple diagnostic index. A database consisting of 500 patients with untreated
      biopsy-proven chronic non-A non-B hepatitis was used. Liver biopsies were
      reviewed, blind, by a panel of pathologists. Patients were classified according
      to the presence of necroinflammatory lesions (histological activity) and
      fibrosis. The diagnostic value of nine clinical and 10 biological factors was
      assessed using logistic regression analysis, sensitivity, specificity and
      predictive values, and a score was constructed combining the most significant
      factors identified. The validation used an independent population of 120
      patients. Serum platelet concentration and age were the two main factors
      significantly and independently correlated with the presence of fibrosis and/or
      histological activity. A simple score referred to as AP, combining age and
      platelet count, varied from 0-10. For the presence of significant histological
      disease (moderate to severe necroinflammatory lesions and/or septal fibrosis to
      cirrhosis), an AP score of 6 or more had a specificity of 0.93 and a sensitivity
      of 0.52%. In the validation population, the area under the curve was 0.690 +/-
      0.085, not significantly different from that of the first population, 0.763 +/-
      0.043. Hence, a simple score combining age and platelet count enabled the
      accurate prediction of the presence of activity and fibrosis in patients infected
      with the hepatitis C virus. When this score reached 6, liver biopsy could be
      avoided owing to its high predictive value. However, the negative predictive
      value was not high enough to prevent a liver biopsy in patients with a lower
      score.

PMID- 9181530
TI  - Human leucocyte interferon-alpha in chronic hepatitis C resistant to recombinant
      or lymphoblastoid interferon-alpha: a randomized controlled trial.
AB  - Patients with biopsy-proven chronic hepatitis C, who failed to respond to a
      previous course of either recombinant (rIFN-alpha) or lymphoblastoid (Ly IFN
      alpha) interferon-alpha, were randomized to receive either leucocyte (Le) IFN
      alpha (patients) or a second course of the same IFN-alpha (controls), to compare
      the efficacy and safety of these treatment schedules. All patients received the
      same dose of IFN-alpha as was used during their previous treatment (3 million
      units (MU) or 6 MU three times weekly) for 6 months. Patients with a normal
      alanine aminotransferase (ALT) value at month 6 were treated for a further 6
      months. All patients were followed-up for 12 months after treatment. A total of
      69 patients were enrolled, 44 in the Le IFN-alpha group and 25 in the control
      group. At the end of the treatment period, 13 of the 44 patients (29.5%) in the
      Le IFN-alpha group had a biochemical response (normal ALT) and six of 44 (13.6%)
      patients had undetectable serum hepatitis C virus (HCV) RNA. At the end of the
      follow-up period, 10 patients (22.7%) had normal ALT values and serum HCV RNA was
      undetectable in three (6.8%). None of the patients in the control group showed
      normal ALT values at any time. Genotype 1b tended to be more frequent among non
      responders (61 vs 45%): basal gamma-glutamyl transpeptidase (gamma-GT) values
      were lower in responders than in non-responders (33.3 +/- 11.70 Ul-1 vs 58.4 +/-
      33.04; P = 0.01). Le IFN-alpha was well tolerated by all patients. These results
      support the use of Le IFN-alpha in patients with chronic hepatitis C who are non
      responders to a previous treatment with recombinant or lymphoblastoid IFN-alpha.

PMID- 9181531
TI  - The "singing-acting" child: the laryngologist's perspective--1995.
AB  - A survey of pediatric otolaryngologists about voice disorders in children
      suggests that approximately 1% of children examined were noted to have voice
      problems, and in only one fifth of these children (0.2%) were the voice problems
      related to professional use of the voice, such as singing. Direct flexible
      laryngoscopy was the sole method of examination for 80% of the children examined
      by these pediatric specialists. Voice therapy for 6 months was generally
      recommended (88%). The survey represents an estimated clinical experience of >
      160,000 children per year, and it achieved a response rate of 40% of pediatric
      otolaryngologists (48/120). Results suggest that the use of video and stroboscopy
      for examination of the pediatric voice would enhance understanding and assure
      correct diagnosis and treatment.

PMID- 9181532
TI  - The singing/acting child: a speech-language pathologist's perspective.
AB  - Performance-oriented children who encounter voice problems benefit from a team
      approach to intervention. Developmental and psychosocial issues in addition to
      the acquisition of information and vocal skills must be addressed. This article
      presents information from a speech-language pathologist's perspective and
      includes some examples of clinical approaches and strategies. The importance of
      building motivation to change vocal habits and the need for the child to develop
      insight and self-evaluation strategies is emphasized.

PMID- 9181533
TI  - The singing teacher as vocal parent.
AB  - Vocal parenting is a pedagogical approach that views the teaching of singing to
      children as a nurturing process. It encompasses the development of fundamentally
      sound vocal technique, guidance in repertoire selection and performance
      practices, and concern for the physical, mental, and emotional well-being of the
      child as a singer, performer, and person. Role-play and storytelling are among
      the strategies employed to fully integrate vocal technique with the personality
      of the singer.

PMID- 9181534
TI  - The young adult voice.
AB  - Young adulthood is notable for rapid physical changes and psychosocial
      instability. Care of the young adult professional voice requires knowledge of the
      specific anatomic and physiologic changes associated with the mutational voice,
      as well as the effects of general growth and maturation on the vocal mechanism.
      The effects of psychological stresses common to young adulthood, such as
      educational commitments and early career choices, must also be understood. Upper
      respiratory infection and allergies are common in this age group. Treatment of
      these conditions must be tailored in the professional voice user because of the
      potential side effects of some medications and the performance imperatives of the
      patient. Surgical indications for tonsillectomy in the young voice patient are
      discussed. There are no special considerations in the evaluation and treatment of
      laryngeal pathology in the young adult, with the exception of limiting the use of
      sedative anesthesia. However, conservatism in surgical decision-making is
      advised. The development of a stable, efficient vocal technique and a mature
      professional background requires time, patience, and hard work.

PMID- 9181535
TI  - The young adult patient.

PMID- 9181536
TI  - The singing/acting young adult from a singing instruction perspective.

PMID- 9181537
TI  - The aging adult voice.
AB  - Advancing age produces physiologic changes that may alter voice. Some of these
      changes are inevitable; others may be avoidable or reversible. In addition, many
      treatable medical conditions may cause voice changes similar to those of aging.
      It is essential that all voice care providers be familiar with the expected
      changes of aging, and be alert to reversible conditions that may adversely affect
      phonation and be mistaken for presbyphonia.

PMID- 9181538
TI  - The singing/acting voice in the mature adult.
AB  - With years of training and performance, the mature vocal performer experiences
      less vocal changes with aging than does his/her age peer who is not a performer.
      We have considered, some physical problems that may adversely influence the voice
      of the older performer. With some awareness and effective management of these
      possible problems, the negative effects on the older performer's voice can be
      minimized.

PMID- 9181539
TI  - The singing/acting mature adult--singing instruction perspective.
AB  - Complete knowledge of anatomy and physiology of the vocal mechanism and tract is
      essential for the voice teacher to be maximally effective. Possible contributing
      factors to vocal attrition in the mature singer/actor are outlined: poor posture,
      inadequate respiratory function, lack of adequate hydration, phonatory
      hyperfunction, habitual speaking pitch at too low a frequency, lack of resonance,
      tongue tension affecting phonation, resonation, and articulation. Techniques for
      rehabilitation of the damaged voice are recommended.

PMID- 9181540
TI  - Physiological aspects of a vocal exercise.
AB  - The physiological aim of vocal exercises is mostly understood in intuitive terms
      only. This article presents an attempt to document the phonatory behavior induced
      by a vocal exercise. An elevated vertical position of the larynx is frequently
      associated with hyperfunctional phonatory habits, presumably because it induces
      an exaggerated vocal fold adduction. Using the multichannel electroglottograph
      (MEGG), the laryngeal position was determined in a group of subjects who
      performed a voice exercise that contained extremely prolonged versions of the
      consonant/b:/. This exercise is used by the coauthor (N.E.) as part of a standard
      vocal exercise program. Two of the seven subjects were dysphonic phonastenic
      patients, and the rest were normal trained or untrained persons. Different
      attempts to calibrate the MEGG confirmed a linear relationship with larynx
      height, provided electrode positioning was correct. The results showed that the
      exercise induced substantial vertical displacements of the larynx. Comparison
      with larynx height during voicing of other consonants showed that the/b/, in
      particular, tended to lower the larynx.

PMID- 9181541
TI  - Comparisons of intensity measures and their stability in male and female
      speakers.
AB  - The purpose of the present study was to provide data on the intensity
      characteristics of young adult speakers in terms of conversational intensity
      level, conversational intensity range, and available intensity range. Subjects
      included 20 males and 20 females, ages 20-30 years. Each subject was asked to
      read the Rainbow Passage at a conversational intensity level, as softly as
      possible without whispering, and as loudly as possible, on 2 separate days 1 week
      apart. The second and third sentences of the three readings on both days were
      analyzed for various intensity parameters. Results revealed a conversational
      intensity level of 70.42 dB for males and 68.15 dB for females. When male and
      female intensity measures were compared, few statistically significant
      differences were found. Further, when intensity measures for the first and second
      readings were compared, few significant differences were found.

PMID- 9181542
TI  - Pressure-flow relationships during phonation as a function of adduction.
AB  - Pressure-flow relationships were obtained for five excised canine larynges.
      Simultaneous recordings were made of average subglottal pressure, average air
      flow, and the electroglottograph at various levels of adduction and vocal fold
      lengths. The level of adduction was controlled by positioning the arytenoid
      cartilages via laterally imbedded three-prong attachments and by the use of intra
      arytenoid shims. Adduction was quantified by measuring the vocal process gap.
      Results indicated a linear pressure-flow relationship within the experimental
      range of phonation for each level of adduction. Differential glottal resistance
      increased as the vocal process gap was reduced. A model is presented for the
      differential resistance as a hyperbolic function of vocal process gap. The
      pressure-flow relationship and the model can be used in computer simulations of
      speech production and for clinical insight into the aerodynamic function of the
      human larynx.

PMID- 9181543
TI  - Speech breathing during reading in women with vocal nodules.
AB  - This study examined speech breathing patterns during reading by women with
      bilateral vocal fold nodules judged as mildly dysphonic and by women without
      vocal nodules. Although it might be predictable that the speech breathing
      patterns of individuals with laryngeal dysfunction will differ from those without
      laryngeal dysfunction, there is a lack of empirical data to support such
      assumptions. The results of the current study indicated that glottal airflow was
      greater during reading for the women with vocal nodules and that a larger volume
      of air was expended both per syllable and per breath group during reading. The
      rate of speech did not significantly differ between the two groups of women.
      There was no significant difference for the average duration of the breath groups
      and no significant difference for the number of syllables spoken per breath
      group. Additionally, both groups of women demonstrated a similar pattern of
      inspiratory pause location during the reading. The results suggest that speech
      breathing patterns associated with dysphonia be examined independently to
      distinguish specifically the nature of the interaction between the laryngeal
      dysfunction and the speech breathing pattern. Certainly, more information on how
      the severity of a voice disorder influences speech breathing is necessary.

PMID- 9181544
TI  - Voice F0 responses to pitch-shifted auditory feedback: a preliminary study.
AB  - Auditory feedback has been suggested to be important for voice fundamental
      frequency (F0) control. The present study featured a new technique for testing
      this hypothesis by which the pitch of a subject's voice was modulated, fed back
      over earphones, and the resultant change in the emitted voice F0 was measured.
      The responses of 67 normal, healthy young adults were recorded as they attempted
      to ignore intermittent upward or downward shifts in pitch feedback while they
      sustained steady vowel sounds (/a/) or sang musical scales. Ninety-six percent of
      subjects increased their F0 when the feedback pitch was decreased, and 78% of
      subjects decreased their F0 when the pitch feedback was increased. Latencies of
      responses ranged from 104 to 223 ms. Results indicate people normally rely on
      pitch feedback to control voice F0.

PMID- 9181545
TI  - Movement of the velum during speech and singing in classically trained singers.
AB  - The present study addresses two questions: (a) Is the action and/or posture of
      the velopharyngeal valve conducive to allow significant resonance during Western
      tradition classical singing? (b) How do the actions of the velopharyngeal valve
      observed in this style of singing compare with normal speech? A photodetector
      system was used to observe the area function of the velopharyngeal port during
      speech and classical style singing. Identical speech samples were produced by
      each subject in a normal speaking voice and then in the low, medium, and high
      singing ranges. Results indicate that in these four singers the velopharyngeal
      port was closed significantly longer in singing than in speaking samples. The
      amount of time the velopharyngeal port was opened was greatest in speech and
      diminished as the singer ascended in pitch. In the high voice condition, little
      or no opening of the velopharyngeal port was measured.

PMID- 9181546
TI  - Acoustic analysis of voice in individuals with amyotrophic lateral sclerosis and
      perceptually normal vocal quality.
AB  - Currently, early phonatory changes in amyotrophic lateral sclerosis (ALS) are not
      well understood. The aim of this study was to compare acoustic parameters of
      voice in ALS subjects who demonstrated perceptually normal vocal quality on
      sustained phonation with a control group. We hypothesized that objective analysis
      of voice would reveal significant differences on specific acoustic parameters of
      voice compared to the control group. Results revealed statistically significant
      differences between the two groups on measures related to frequency range and
      phonatory stability. The findings suggest that early bulbar signs affecting the
      laryngeal system may be present in patients with ALS before the occurrence of
      perceptually aberrant vocal characteristics.

PMID- 9181547
TI  - Adductor spasmodic dysphonia: case reports with acoustic analysis following
      botulinum toxin injection and acupuncture.
AB  - We analyzed frequency and duration parameters of voice and speech in two men with
      adductor spasmodic dysphonia (SD). One was treated with botulinum toxin
      injection; the other received acupuncture therapy. Improvement after acupuncture
      therapy in terms of standard deviation of fundamental frequency, acoustic
      perturbation measurements, durational measurements of voice and speech, and
      spectrographic analysis was comparable to the results achieved with botulinum
      toxin injection. Voice and speech parameters were stable 1 year after acupuncture
      therapy.

PMID- 9181548
TI  - Autologous fat implantation for vocal fold scar: a preliminary report.
AB  - New insights into the anatomy and physiology of phonation, along with
      technological advances in voice assessment and quantification, have led to
      dramatic improvements in medical voice care. Techniques to prevent vocal fold
      scar have been among the most important, especially scarring and hoarseness
      associated with voice surgery. Nevertheless, dysphonia due to vocal fold scar is
      still encountered all too frequently. Although it is not generally possible to
      restore such injured voices to normal, patients with scar-induced dysphonia can
      usually be helped. Voice improvement is optimized through a team approach.
      Treatment may include sophisticated voice therapy and vocal fold surgery.
      Although experience with collagen injection has been encouraging in selected
      cases (particularly in those involving limited areas of vocal fold scar), there
      is no consistently successful surgical technique. Attempts to treat massive vocal
      fold scar, such as may be seen following vocal fold stripping, have been
      particularly unsuccessful. This paper reports preliminary experience with the
      implantation of autologous fat into the vibratory margin of the vocal fold of
      patients with severe, extensive scarring. Using this technique, it appears
      possible to recreate a mucosal wave and improve voice quality. Additional
      research is needed.

PMID- 9181549
TI  - Analysis of proteoglycan messages in human articular cartilage by a competitive
      PCR technique.
AB  - A competitive PCR technique has been established to allow quantitation of message
      levels within tissues without the need for cell isolation. The method utilizes an
      internal RNA standard that uses the same oligonucleotide primers as the authentic
      message for both reverse transcription and DNA polymerization. While the
      technique does not give absolute message levels when applied to intact tissues,
      because of incomplete extraction yields, it can be used to give values relative
      to any reference message level. The technique has been applied to the analysis of
      the message levels for aggrecan, versican, link protein, decorin, biglycan,
      fibromodulin and lumican in human articular cartilage isolated from individuals
      ranging in age from the neonate to the mature adult. The data indicate that the
      messages for versican and link protein are always present in lesser abundance
      than that for aggrecan, and while the aggrecan message levels tend to increase in
      the adult, those for versican and link protein do not. With respect to the family
      of leucine-rich repeat proteoglycans, the message for decorin is by far the most
      abundant at all ages and shows a marked increase in abundance in the adult
      relative to the juvenile. The messages for fibromodulin and lumican also show
      increased abundance in the adult, whereas that for biglycan shows no marked age
      related trend. The message levels for decorin were also higher than those for
      aggrecan at all ages.

PMID- 9181550
TI  - Eggshells are shaped by a precise spatio-temporal arrangement of sequentially
      deposited macromolecules.
AB  - The avian eggshell is a composite bioceramic which is formed by a controlled
      interaction of an organic and an inorganic phase. The organic phase contains,
      among other constituents, type X collagen and proteoglycans, mainly keratan and
      dermatan sulfate. Understanding the principles governing the synthesis and
      temporo-spatial distribution of such macromolecules, and their influence on the
      organization of the crystalline phase, is an essential aspect of establishing the
      biological basis of the quality of eggshell, both as an embryonic chamber and as
      a natural food package. In the present study, we have examined the process of
      eggshell formation by immunohistochemistry, scanning electron microscopy and
      energy dispersive X-ray microanalysis. Precise sites and timing of secretion were
      established for the deposition of particular macromolecules. Type X collagen is
      detected at the very first moment of shell membrane formation. The appearance of
      keratan sulfate coincides with the appearance of mammillae, while dermatan
      sulfate is deposited later, coincident with shell matrix deposition. We propose
      that keratan sulfate, due to its precise localization, temporal appearance and
      calcium-binding affinity, relates to the maintenance of calcium reserve bodies,
      the primary source of calcium for the embryo. On the other hand, dermatan sulfate
      may control crystal growth, resulting in a preferential orientation of calcite
      crystals within the palisade layer.

PMID- 9181551
TI  - Attachment of osteoblastic cells to hydroxyapatite crystals by a synthetic
      peptide (Glu7-Pro-Arg-Gly-Asp-Thr) containing two functional sequences of bone
      sialoprotein.
AB  - We investigated activity of bone sialoprotein (BSP) to mediate attachment of
      cells to hydroxyapatite using a model peptide, Glu7-Pro-Arg-Gly-Asp-Thr, which
      contains a putative hydroxyapatite-binding site (poly-Glu) and a cell-attachment
      site. The peptide has affinity to hydroxyapatite with a dissociation constant of
      13.5 microM. The peptide affected in vitro mineralization in a gel system,
      indicating interaction between this peptide and calcium phosphate. The
      osteoblastic cell line MC3T3-E1 was incubated with hydroxyapatite powder coated
      with the peptide or proteins. Attachment of the cells was observed on the powder
      coated with BSP, but not on the powder coated with serum albumin. The cells were
      attached to the powder coated with the peptide. The cells were flattened on the
      powder, and pseudopods developed. The attachment of the cells was inhibited by an
      excessive amount of Gly-Arg-Gly-Asp-Ser peptide. In conclusion, BSP mediated
      attachment of osteoblastic cells to hydroxyapatite, and this activity could be
      accomplished only by the poly-Glu sequence and the Arg-Gly-Asp sequence.

PMID- 9181552
TI  - Characterization of human type II procollagen and collagen-specific antibodies
      and their application to the study of human type II collagen processing and
      ultrastructure.
AB  - Type II collagen is the most abundant collagen in articular cartilage and,
      together with other tissue-specific collagens and proteoglycans, provides the
      tissue with its shock-absorbing properties and its resiliency to stress. Specific
      antibodies which recognize various collagen types have been very useful in the
      study of collagen biosynthesis, structure and metabolism in normal and
      pathological conditions. Antibodies which recognize epitopes of type II collagen
      have been described previously; however, many of these antibodies display cross
      reactivity with other collagens or with type II collagen from other species,
      reflecting the high degree of homology of the helical domains of fibrillar
      collagens. In this study, we prepared antibodies to sequential determinants of
      human type II procollagen employing synthetic peptides with sequences deduced
      from the nucleotide sequence of the human alpha 1 (II) procollagen cDNA. The
      antibodies were highly specific for epitopes in either the C-terminal propeptide
      or the telopeptide of the human type II collagen and did not cross-react with
      other human interstitial collagens or with murine type II collagen. These
      antibodies were used in conjunction with biosynthetic labeling to study the
      secretion and processing of human type II procollagen and collagen in human
      chondrocytes in vitro. The results indicated that a lag period of about 90 min
      was required for the secretion of newly synthesized type II procollagen.
      Conversion of the secreted procollagen into fully processed alpha-chains and
      their deposition in the cell layer were first apparent 240 min following the
      initiation of biosynthetic labeling. The antibodies were also used to examine, by
      immunoelectron microscopy, the structure of the extracellular matrix produced by
      human chondrocytes maintained in long-term cultures under conditions which permit
      the preservation of the cartilage-specific phenotype. These highly specific
      antibodies provide valuable tools to study the metabolism and structure of human
      type II procollagen and collagen in normal and pathologic conditions.

PMID- 9181553
TI  - The CUB domains of procollagen C-proteinase enhancer control collagen assembly
      solely by their effect on procollagen C-proteinase/bone morphogenetic protein-1.
AB  - Procollagen C-proteinase enhancer (PCPE) is a 55 kDa glycoprotein that increases
      the activity of procollagen C-proteinase (PCP)/bone morphogenetic protein-1 (BMP
      1) during C-terminal processing of fibrillar collagen precursors. Here we show
      that the 36 kDa, active fragment of PCPE enhances the activity of both the short
      (mouse) and long (chick) forms of PCP/BMP-1. The activity of PCPE is not
      associated with the formation of sedimentable procollagen aggregates. In
      addition, PCPE (36 kDa) has no effect in vitro on N-terminal procollagen
      processing by highly purified procollagen N-proteinase. Finally, when the amount
      of PCP is adjusted so that the rate of C-terminal processing remains constant,
      PCPE (36 kDa) has no effect on the assembly of collagen or pN-collagen in vitro
      following C-terminal processing of the corresponding precursors.

PMID- 9181555
TI  - Novartis' role in 21st century drug development.

PMID- 9181554
TI  - Translating genomics information into therapeutics: a key role for
      oligonucleotides.

PMID- 9181556
TI  - The EPA's war on bioremediation.

PMID- 9181557
TI  - Cloning our way to "the next level".

PMID- 9181558
TI  - FDA and Pharmanex clash over dietary supplement.

PMID- 9181559
TI  - Cephalon adds to clinical disappointment in 1997.

PMID- 9181560
TI  - Amgen protects its billion dollar protein.

PMID- 9181561
TI  - Gene activation and EPO.

PMID- 9181562
TI  - Whitehead consortium to develop new genome tools.

PMID- 9181563
TI  - EPA issues, USDA amends respective biotech rules.

PMID- 9181564
TI  - Conflicts brewing as phage display gets complex.

PMID- 9181565
TI  - Blood products have future despite recent setbacks.

PMID- 9181566
TI  - Many are probed, but few are chosen.

PMID- 9181567
TI  - Addressing tumor blood vessels.

PMID- 9181568
TI  - A quick fix using random DNA amplification.

PMID- 9181569
TI  - Trick and treat: toward peptide mimic vaccines.

PMID- 9181570
TI  - Rethinking the development of breast cancer.

PMID- 9181571
TI  - Cancer researchers validate and pursue telomerase.

PMID- 9181572
TI  - Antisense '97: a roundtable on the state of the industry.

PMID- 9181573
TI  - Metabolic engineering and human disease.

PMID- 9181574
TI  - From housekeeper to microsurgeon: the diagnostic and therapeutic potential of
      ribonucleases.
AB  - The RNA population in cells is controlled post-transcriptionally by ribonucleases
      (RNases) of varying specificity. Angiogenin, neurotoxins, and plant allergens are
      among many proteins with RNase activity or significant homology to known RNases.
      RNase activity in serum and cell extracts is elevated in a variety of cancers and
      infectious diseases. RNases are regulated by specific activators and inhibitors,
      including interferons. Many of these regulatory molecules are useful lead
      compounds for the design of drugs to control tumor angiogenesis, allergic
      reactions, and viral replication. One RNase (Onconase) and several RNase
      activators are now in clinical trials for cancer treatment or inhibition of
      chronic virus infections. Several others, alone or conjugated with specific cell
      binding molecules, are being developed for their antifungal, antiviral, and
      antitumor cell activity.

PMID- 9181575
TI  - Selecting effective antisense reagents on combinatorial oligonucleotide arrays.
AB  - An array of 1,938 oligodeoxynucleotides (ONs) ranging in length from monomers to
      17-mers was fabricated on the surface of a glass plate and used to measure the
      potential of oligonucleotide for heteroduplex formation with rabbit beta-globin
      mRNA. The oligonucleotides were complementary to the first 122 bases of mRNA
      comprising the 5' UTR and bases 1 to 69 of the first exon. Surprisingly few
      oligonucleotides gave significant heteroduplex yield. Antisense activity,
      measured in a RNase H assay and by in vitro translation, correlated well with
      yield of heteroduplex on the array. These results help to explain the variable
      success that is commonly experienced in the choice of antisense oligonucleotides.
      For the optimal ON, the concentration required to inhibit translation by 50% was
      found to be five times less than for any other ON. We find no obvious features in
      the mRNA sequence or the predicted secondary structure that can explain the
      variation in heteroduplex yield. However, the arrays provide a simple empirical
      method of selecting effective antisense oligonucleotides for any RNA target of
      known sequence.

PMID- 9181576
TI  - Alpha v integrins as receptors for tumor targeting by circulating ligands.
AB  - Phage displaying an Arg-Gly-Asp (RGD)-containing peptide with a high affinity for
      alpha v integrins homed to tumors when injected intravenously into tumor-bearing
      mice. A substantially higher amount of alpha v-directed RGD phage than control
      phage was recovered from malignant melanomas and breast carcinoma. Antibodies
      detected the alpha v-directed RGD phage in tumor blood vessels, but not in
      several normal tissues. These results show that the alpha v integrins present in
      tumor blood vessels can bind circulating ligands and that RGD peptides selective
      for these integrins may be suitable tools in tumor targeting for diagnostic and
      therapeutic purposes.

PMID- 9181577
TI  - Peptide mimicry of carbohydrate epitopes on human immunodeficiency virus.
AB  - Cancer-related, mucin-type carbohydrate epitopes, principally mannose and sialo
      syl residues, are expressed on the envelope protein gp 160 of the human
      immunodeficiency virus (HIV). Anticarbohydrate antibodies directed toward these
      and other carbohydrate epitopes are known to neutralize HIV-1 infection by cell
      free virus. Carbohydrates, however, being T cell-independent antigens, typically
      elicit diminished immune responses. To overcome this potential draw back, we have
      examined the ability of peptides that mimic such epitopes to elicit immune
      responses that cross-react with carbohydrate structures. We report that mouse
      polyclonal antisera generated against peptides that mimic mucin-related
      carbohydrate epitopes have anti-HIV-1 activity. Generation of antibodies was not
      lr-gene restricted, as at least two different strains of mice. Balb/c (H-2d) and
      C57Bl/6 (H-2b), responded equally to the peptides. The antipeptide sera displayed
      neutralizing activity against HIV-I/MN and HIV-I/3B viral strains. This
      neutralization was as good as human anti-HIV sera. These results indicate that
      peptide mimics of carbohydrates provide a novel strategy for the further
      development of reagents that elicit immune responses to carbohydrate epitopes
      associated with many infectious organisms and tumor cells.

PMID- 9181578
TI  - Yeast surface display for screening combinatorial polypeptide libraries.
AB  - Display on the yeast cell wall is well suited for engineering mammalian cell
      surface and secreted proteins (e.g., antibodies, receptors, cytokines) that
      require endoplasmic reticulum-specific post-translational processing for
      efficient folding and activity. C-terminal fusion to the Aga2p mating adhesion
      receptor of Saccharomyces cerevisiae has been used for the selection of scFv
      antibody fragments with threefold decreased antigen dissociation rate from a
      randomly mutated library. A eukaryotic host should alleviate expression biases
      present in bacterially propagated combinatorial libraries. Quantitative flow
      cytometric analysis enables fine discrimination of kinetic parameters for protein
      binding to soluble ligands.

PMID- 9181579
TI  - Use of a modified bacteriophage to probe the interactions between peptides and
      ion channel receptors in mammalian cells.
AB  - Besides natural peptide ligands, screening of random peptide libraries has
      yielded novel bioactive peptides for cell surface receptors. A method is
      described that uses a modified bacteriophage as a detection reagent to monitor
      the expression of receptor channels in mammalian cells and to probe the molecular
      interaction between phage-tethered peptides (phi T-peptides) and specific
      receptor targets. By taking advantage of a specific multivalent interaction
      between phi T-peptides and the receptor target, assays have been developed that
      use phi T-peptides specific for the N-methyl-D-aspartate glutamate receptor, an
      important ligand-gated ion channel in the nervous system, to monitor the receptor
      expression in cultured mammalian cells. Combining these phi T-peptide binding
      assays with fluorescence-activated cell sorting, 10(4) random glutamate receptor
      mutants were screened and candidate interaction residues were identified. This
      dual heterologous expression system offers a powerful approach to the molecular
      studies of protein-protein interactions.

PMID- 9181580
TI  - Generation of Rhizobium strains with improved symbiotic properties by random DNA
      amplification (RDA)
AB  - To select for bacterial strains with enhanced phenotypes, random fragments of a
      whole genome, or a defined region of the genome, are cloned in a nonreplicating
      vector. The resulting plasmids are integrated by recombination into the
      homologous DNA region of the original strain. Integration gives rise to a
      nontandem direct duplication of the corresponding DNA region separated by the
      vector moiety of the plasmid. Recombination between the direct repeats leads to
      tandem duplication and further amplification of the entire integrated DNA,
      including the vector. Bacteria harboring the amplified DNA are selected by
      increasing the dosage of an antibiotic corresponding to a resistance marker of
      the integrated vector. Pooled strains carrying amplifications are then challenged
      with a selective pressure for the desired phenotype. After repeated selection
      cycles, the most fit strains are isolated. We used this process, which we called
      random DNA amplification, to select Rhizobium strains with increased
      competitiveness for nodule formation. Derivatives containing randomly amplified
      DNA regions of the symbiotic plasmid of Rhizobium tropici CFN299 strain were
      generated. Pools of amplified strains were inoculated onto various tropical
      legumes. After several cycles of selection through plants, amplified derivatives
      showing an increased competitiveness for nodule formation with the leguminous
      plant Macroptilium atropurpureum were obtained.

PMID- 9181581
TI  - Augmentation of blood platelet levels by intratracheal administration of an
      adenovirus vector encoding human thrombopoietin cDNA.
AB  - This study was designed to evaluate the hypothesis that administration of a
      replication-deficient, recombinant adenovirus vector to the epithelial surface of
      the respiratory tract can be used to deliver a recombinant protein to the
      systemic circulation in sufficient quantities to evoke a systemic response
      appropriate to the recombinant protein. We administered AdCMV.TPO-an adenovirus
      vector containing an expression cassette coding for the human thrombopoietin
      (TPO) cDNA-to the respiratory epithelium of immunocompetent Balb/c mice. Over the
      following week, serum human TPO levels were elevated, platelet levels increased
      more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy
      may be a useful approach to the nonparenteral administration of a variety of
      therapeutic recombinant proteins, such as those relevant to clotting, endocrine
      function, and bone-marrow function.

PMID- 9181582
TI  - Bipotent progenitor cell lines from the human CNS.
AB  - Human central nervous system (CNS) cell lines would substantially facilitate drug
      discovery and basic research by providing a readily renewable source of human
      neurons. We isolated clonal human CNS cell lines that had been immortalized with
      a tetracycline (Tc)-responsive v-myc oncogene; addition of Tc to the growth
      medium suppressed the oncoprotein rapidly and virtually completely, allowing
      differentiation to proceed. Two classes of bipotent precursor cells were
      immortalized: the first class had a default differentiation pathway of neurons
      only, and the second class had a default differentiation pathway of neurons and
      astrocytes. We found that after exposure to different external signals in vitro,
      the environment is capable of redirecting the fate of a particular cell, even in
      the case of the bipotent precursor cell whose default differentiation pathway was
      neurons only. These data suggest that extrinsic cues can prevail over intrinsic
      determinants in directing cell fate in the human CNS.

PMID- 9181584
TI  - Patenting DNA: just when you thought it was safe.

PMID- 9181583
TI  - Manipulating the aggregation and oxidation of human SPARC in the cytoplasm of
      Escherichia coli.
AB  - Human SPARC (secreted protein acidic and rich in cysteine), an extracellular
      matrix protein containing 14 cysteine residues, was found to partition equally
      between soluble and insoluble cellular fractions when overexpressed in the
      Escherichia coli cytoplasm. While the growth temperature and medium pH had little
      effect on inclusion body formation, co-overproduction of the dnaKJ operon, but
      not of the groE operon, suppressed aggregation at the expense of intracellular
      accumulation. Although both forms of the protein were fully reduced in wild-type
      cells, 70% to 85% of soluble and insoluble SPARC could be converted into oxidized
      species in a thioredoxin reductase (trxB) null mutant following incubation on
      ice. Approximately 15% to 20% of SPARC exhibited the electrophoretic mobility of
      the biologically active protein. Overproduction of the dnaKJ operon in trxB cells
      decreased the formation of disulfide-bonded SPARC multimers in the aggregated
      material but not in its soluble counterpart. Our results suggest that the
      activity responsible for disulfide bond formation in trxB mutants acts at the
      post-translational level and is able to freely diffuse within inclusion bodies.

PMID- 9181585
TI  - Chiral-based therapeutics.

PMID- 9181586
TI  - [Gene therapy and neurosurgery].

PMID- 9181587
TI  - [Surgical strategy of the AVM on the sensori motor cortex].

PMID- 9181588
TI  - [Changes in metabolism and peritumoral circulation after radiosurgery of
      metastatic brain tumors: evaluation by three dimensional dual isotope SPECT].
AB  - Concurrent use of two different isotopes, 201T1C1 and 123I-IMP, in SPECT is
      useful in separative evaluation of tumor metabolism and peritumoral circulation.
      Three dimensional SPECT employed in our study has an obvious advantage over two
      dimensional SPECT for its accurate imaging of tumors and peritumoural areas.
      Changes of tumor metabolism and regional circulation in peritumoral edematous
      tissues were investigated by fused 3-D SPECT images using 201T1C1 and 123I-IMP.
      In this study, the volume of isotope accumulative and isotope defective regions
      were measured. Fusion of SPECT images was performed by the use of panning
      visualization software; Application Visualization System Medical View (K.G.T.).
      The threshold of 3-D rendering was determined by conforming the volume of the
      hemisphere and of the tumor estimated on CT to the volume of 123I-IMP and 201T1C1
      accumulating area respectively. Accumulative volume of 201T1C1 in the tumor
      decreased remarkably at 7 days after radiosurgery (p < 0.01). Defective volume of
      peritumoral hypoperfusion was measured on 3-D SPECT. The average volume was 80.5
      + 32.5cm3 before radiosurgery. It decreased by approximately 60% at 7 days after
      radiosurgery (p < 0.05). Analysis of 3-D SPECT images using two different isotope
      tracers is reliable and useful to evaluate early the changes of metabolism and
      peritumoral circulation in or around intracerebral tumors.

PMID- 9181589
TI  - [The effect of hypothermia on CSD propagation in rats].
AB  - In the cortical zone surrounding an ischemic or traumatic focus, CSD is a
      transient phenomenon involving interstitial ions, blood flow and metabolism and
      is believed to be completely reversible. However, it may extend to secondary
      brain injuries because CSD releases excitatory amino acids into the extracellular
      space. In order to prevent secondary brain injuries, it may be effective to block
      repeated CSD. This study was designed to determine whether hypothermia can block
      CSD propagation and whether this study is a potentially useful means for
      preventing secondary brain injuries. Male wistar rats weighing 270 g on average
      were used for the experiments. The animals were divided into two groups:
      hypothermic rats (33.5-34 degrees C, rectal temp.) and normothermic rats (37-37.5
      degrees C). The changes in rCBF (regional Cerebral Blood Flow) were monitored in
      order to observe CSD. LDF (Laser Doppler Flowmetry) was used to measure rCBF. The
      two LDF probes were placed on the parietal cortex (4 mm apart). To elicit CSD, a
      needle stab injury was made on the cortex or a piece of paper soaked with 10% KCl
      was applied on the cortex. The velocity of CSD propagation was more prolonged in
      the hypothermic rats than in the normothermic rats (p < 0.01). There were smaller
      numbers of repeated CSD in the hypothermic rats than in the normothermic rats.
      Histological examination of the cerebral cortex revealed shrinkage neurons more
      distinctly in the normothermic rats than in hypothermic rats. From these results,
      we can speculate that hypothermic may block CSD propagation and that hypothermic
      therapy has the potential to prevent secondary brain injuries.

PMID- 9181590
TI  - [Analysis of mild barbiturate-moderate hypothermia therapy on the authors' 152
      cases].
AB  - Mild barbiturate-moderate hypothermia therapy was established for severe head
      injury and cerebrovascular disease. This study was conducted on 152 patients from
      April 1984 through July 1995. In this study were included patients with Glagow
      Coma Scale score of less than 8 points but those with serious systemic
      complications and elderly and infantile patients were excluded. Our protocol
      consisted of administration of thiamylal Na 1.25-2.5 mg/kg/h and droperidol 20-40
      micrograms/kg/h (mild barbiturate) while maintaining a core temperature of 32-34
      degrees C (moderate hypothermia). The clinical outcome was good (GR, MD) in 58
      cases, poor (SD) in 24 cases and bad (PVS, D) in 70 cases. This therapy was found
      to be particularly effective for preventing ischemic neurological damage in the
      vasospasm stage following SAH and severe head injury in young patients. However,
      this therapy did not prevent pneumonia, cardiac failure, arrhythmia and
      hypopotassemia from occurring frequently. We conclude that this therapy is
      contraindicated in the elderly, i.e., those older than 65 years.

PMID- 9181592
TI  - [A case of cranial osteomyelitis after head injury with exaggeration and
      remission for thirty years].
AB  - We report a case of cranial osteomyelitis after head injury with exaggeration and
      remission for 30 years. A 41-year-old man was referred to our hospital with
      redness, swelling and pain in the left frontal region. He had noted a hard mass
      in the same region after an injury at the age of 12 years, and local heat and
      redness again in the same region which had disappeared without definite treatment
      at the age of 20 years. Presently, skull roentogenogram showed an erosive lesion
      in the left frontal bone. Plain CT revealed bone defect, epidural mass lesion,
      calcification of the dura mater and thickness of the extracranial soft tissue in
      the left frontal region. T1-weighted MR images showed an isointense lesion and T2
      weighted MR images showed a high intensity lesion in the inner table and a
      diploic layer in the left frontal bone. 99thTc MDP bone scinntigram showed
      abnormal uptake in the same region. Operation performed through a left
      frontotemporal craniotomy revealed a degeneration of temporal muscle and frontal
      bone, and granulation tissue and pus in the subcutaneous and epidural spaces.
      These were removed together with the calcified dura mater. The subdural space was
      intact. Dural plasty was performed using fascia lata, but the craniotomied bone
      was replaced. Histological examination revealed typical findings of
      osteomyelitis. Postoperative course was uneventful, and he was discharged without
      neurological deficit. Cranioplasty was performed 8 months after the first
      surgery. The mechanism by which osteomyelitis continued over a long course of
      time was suspected to be the formation of a focus of recurrent inflammation due
      to the head injury 30 years earlier.

PMID- 9181591
TI  - [A ruptured aneurysm of the distal posterior inferior cerebellar artery
      associated with acute subdural hematoma of the posterior fossa: a case report].
AB  - We report a case of distal posterior inferior cerebellar artery (PICA) aneurysm
      associated with acute subdural hematoma (SDH). The patient was a 68-year-old
      female who was found unconscious at home and transferred to the emergency medical
      center in a state of deep coma. Her consciousness on admission to the center was
      200P (Japan coma scale), E1V1M2 (Glasgow Coma Scale), and the Hunt & Kosnik grade
      was grade IV. She was in a state of decerebrate condition. Computed tomography
      (CT) scans revealed diffuse subarachnoid hemorrhage that was located mainly in
      the posterior fossa, as well as intraventricular hemorrhage in the third and
      fourth ventricles. It also disclosed an intracerebellar hematoma (ICH) of the
      vermis and an acute SDH of the left posterior fossa. The first cerebral
      angiographic examinations on admission demonstrated no aneurysm. However,
      emergency surgery was performed immediately in order to improve her poor
      condition. Ventricular drainage and removal of the acute SDH were carried out.
      Postoperatively, her consciousness improved gradually to 20P. Ventricular
      peritoneal shunt was performed three weeks later. Her consciousness improved up
      to 3P and she showed only slight truncal ataxia. She was admitted to our hospital
      for rehabilitation at two months after the first surgery. Repeated angiography
      was performed and demonstrated an aneurysm in the telovelotonsillar segment of
      the left PICA. The aneurysm was successfully clipped via a midline suboccipital
      approach. Her postoperative course was uneventful, and she continues to undergo
      rehabilitation. Aneurysms of the posterior fossa associated with acute SDH are
      extremely rare. Only two cases have been reported for distal PICA aneurysm cases.
      The CT scans in our patient revealed not only SAH but also SDH in the posterior
      fossa and ICH in the vermis. Over 100 cases of distal PICA aneurysms have been
      described in the literature. We analyzed the relationship between the portions
      with the ruptured aneurysms and CT findings. Aneurysms which were located at the
      proximal portion of the distal PICA mainly showed SAH and IVH. On the other hand,
      ICHs of the vermis and cerebellum were characteristic CT findings of ruptured
      aneurysms which were located more distal to the telovelotonsillar segment, and
      were evident in 14% of cases of such aneurysms. ICH and SDH were not found in
      aneurysms which were located in portions more proximal to the telovelotonsillar
      segment. These characteristic findings were related to the complex anatomical
      courses of the PICA. The distal portions of the PICA run between the vermis and
      cerebellar hemisphere, so that if an aneurysm ruptures at these portions, ICHs in
      the vermis and cerebellum tend to occur. In cases such as ours, because of the
      characteristic CT findings, effort to detect a distal PICA aneurysm should be
      made at first surgery, along with ventricular drainage and removal of the SDH.
      The surgical procedures and outcome of cases with distal PICA aneurysms are also
      discussed.

PMID- 9181593
TI  - [A case of pineal teratoma arising from hydrocephalus of unknown cause].
AB  - We report a case of "functional aqueductal stenosis" which reveals dilatation of
      the lateral and 3rd ventricles without stenosis at the aqueduct in MRI. This case
      shows a pineal teratoma which presents one year later with symptoms of
      hydrocephalus caused by "functional aqueductal stenosis". A seven-year-old boy
      was admitted to our department owing to headache and vomiting. CT and MRI showed
      hydrocephalus. The lateral and 3rd ventricles were dilated while the 4th
      ventricle was normal. Furthermore, tumoral obstruction of the aqueduct was not
      found. After a ventriculoperitoneal shunt, he recovered well without neurological
      deficits. One year later, symptoms of precocious puberty, that is the appearance
      of public hair and deepening of his voice, were found. A follow-up MRI
      demonstrated a pineal region tumor. Although human chorionic gonadotropin level
      in the serum and urine was transiently elevated, it normalized before surgery.
      The operation was performed by the occipital transtentorial approach and the
      tumor was totally removed. Histological examination proved this tumor to be a
      mature teratoma, showing three germ cell layers. About two weeks later, he was
      discharged without any neurological deficit. In this case, although hydrocephalus
      occurred, MRI didn't demonstrate aqueductal obstruction caused by the tumor.
      However, one year later, a pineal region tumor was confirmed by MRI. This
      suggests that hydrocephalus might have some association with the appearance of
      the pineal region tumor. Therefore, it is necessary to be aware of the
      possibility of the occurrence of tumors whenever we encounter "functional
      aqueductal obstruction", when MRI doesn't demonstrate aqueductal obstruction
      caused by a tumor.

PMID- 9181594
TI  - [Chondroblastoma of the temporal bone: a case report].
AB  - A 30-year-old male had been suffering from left temporalgia of six months
      duration and then developed left hearing disturbance. Craniogram and bone window
      CT revealed a well defined osteolytic lesion in the left temporal bone. CT scan
      showed an expansile heterogenous mass with calcification. Both T1 and T2 weighted
      MRI demonstrated a well lobulated mixed intensity mass, but no evidence of dural
      or intracranial invasion. The tumor exhibited homogenous enhancement on CT and
      MRI. Angiogram revealed a well marked staining supplied by the left middle
      meningeal and deep temporal arteries. Subtotal removal of the tumor was carried
      out with cranioplasty. Histologically, this tumor was composed of round or
      polygonal chondroblasts, scattered osteoclast-like giant cells with a foci of
      cartilage in the stroma. Many reports describe giant cell tumor can be
      differentiated by immunohistochemical demonstration of S100 protein. Although in
      our case, histological findings simulated those of eosinophilic granuloma, it was
      diagnosed as chondroblastoma because of the foci of cartilage in the stroma.
      Because this tumor is usually benign, recurrence of the tumor is rare after
      surgical resection. Post-operative irradiation has been reported to be effective
      in decreasing the recurrence of the tumor. But it should be carefully observed
      because of possible sarcomatous change in such tumors.

PMID- 9181595
TI  - [A case of meningioma of the jugular foramen without disturbance of lower cranial
      nerves].
AB  - We report a case of meningioma with extracranial extension via the jugular
      foramen not accompanied by any disturbances of the lower cranial nerves. A 32
      year-old female suffered from a headache without any other neurological
      abnormalities. She had no particular family or past history. The extracranial
      extending meningioma was removed at the first operation. The meningioma of the
      jugular foramen was removed at the second staged operation by transcondylar
      approach. A meningioma of the jugular foramen is rare, and the meningioma with
      extracranial extension via the jugular foramen without showing disturbances of
      lower cranial nerves has not been reported so far.

PMID- 9181596
TI  - [Ewing's sarcoma at the occipital bone presenting as acute epidural hematoma: a
      case report].
AB  - Primary cranial Ewing's sarcoma is rare. We describe an exceptionally rare case
      of primary Ewing's sarcoma of the occipital bone, presenting as spontaneous acute
      epidural hematoma. A 19-year-old female was admitted to our hospital complaining
      of sudden onset of severe headache. There were no neurological deficit and no
      abnormal laboratory findings. Computerized tomographic (CT) scan revealed a
      lentiform shaped high density lesion at the left occipital epidural space.
      Magnetic resonance imaging (MRI) showed the lesion as iso to low intensity on T1
      weighted image (T1WI) and mixed signal intensity on T2-weighted image (T2WI).
      There were no pathological findings at the adjacent brain. Cerebral angiography
      demonstrated mass effect. Right occipital craniotomy was performed. We found the
      tumor arising from the occipital bone and located at the epidural space. The
      tumor was resected totally. Histological examination revealed the tumor as
      Ewing's sarcoma with intratumoral hemorrhage. The postoperative course was
      uneventful. Radiation therapy (50Gy) was given. Follow-up examination six years
      after the treatment found no evidence of tumor recurrence or distant metastasis.
      It should be born in mind that primary Ewing's sarcoma of the skull can cause
      spontaneous acute epidural.

PMID- 9181597
TI  - [Perforation of the intestine by a peritoneal tube 10 years after a ventriculo
      peritoneal shunt].
AB  - A case is reported of intestinal perforation by a ventriculoperitoneal shunt (V-P
      shunt) tube 10 years after V-P shunt. A 49-year-old male received V-P shunt for
      normal pressure hydrocephalus following subarachnoid hemorrhage. Ten years later
      he was admitted to our department with an abscess on the anterior chest and on
      the abdominal wall along the shunt tube. When CT scan revealed that the
      peritoneal tube had perforated the bowel, the shunt was removed. During the
      operation it was found that the peritoneal tube was wrapped with fibrous tissue
      and that it had perforated the intestine. The subcutaneous abscess healed after
      the patient received systemic antibiotics. He was discharged and returned to
      work. We discussed the mechanism of bowel perforation in this case. It is assumed
      that bowel perforation occurred because of continuous friction at the same site
      of the bowel wall after the peritoneal tube received fibrous encasement in the
      abdominal cavity. Bowel perforation was diagnosed ten years after the V-P shunt
      in this case. To our knowledge, this is the longest period amongst reported
      cases.

PMID- 9181598
TI  - An appraisal of the pharmacological and toxicological effects of a single oral
      administration of 3,4-methylenedioxymethamphetamine (MDMA) in the rat.
AB  - This study examined some acute pharmacological and toxicological effects of 3,4
      methylenedioxymethamphetamine (MDMA, "Ecstasy") over a range of doses (20, 40,
      80, 160 and 320 mg/kg orally) in adult female rats. Deaths were observed from the
      40 mg/kg MDMA group onwards. Reductions in body weight change, food and water
      intake were found in the 80 mg/kg group, whilst food intake alone was reduced in
      the 20 and 40 mg/kg groups. Significant hyperthermic responses were found over
      the first 8 hr following MDMA administration which were dose-related. A
      significant hyperactivity of approximately 9 hr duration was observed in the 20
      mg/kg and 40 mg/kg groups, whereas there was evidence of a serotonin syndrome in
      the higher dosage groups. Thus, acute oral administration of MDMA results in a
      variety of measurable responses. The cause of death in this study is probably a
      combination of serotonin syndrome and hyperthermia.

PMID- 9181599
TI  - How does cystitis affect a comparative risk profile of tiaprofenic acid with
      other non-steroidal antiinflammatory drugs? An international study based on
      spontaneous reports and drug usage data. ADR Signals Analysis Project (ASAP)
      Team.
AB  - Series of well-documented case reports strongly suggest a causal association
      between tiaprofenic acid and a form of aseptic cystitis, which can cause serious
      and long-term morbidity if the drug is not withdrawn promptly. These findings are
      supported in the Australian and UK spontaneous reporting data-bases. Using sales
      data as the denominator, a comparison of NSAIDs in the WHO drug monitoring data
      base indicates that the reaction is specific to tiaprofenic acid and cannot be
      accounted for by changes in reporting patterns in certain countries or years.
      Delayed recognition is an important feature of this reaction and possible reasons
      for this are discussed. Comparison of the risk profiles of seven NSAIDs indicated
      that tiaprofenic acid had the poorest risk profile, compared with NSAIDs of
      similar efficacy, when cystitis reports were included. The results suggest that
      combining spontaneous reports, classified according to severity, with sales data
      may enhance the ability of drug monitoring data-bases to contribute to risk
      benefit appraisals.

PMID- 9181601
TI  - Renal tolerability profile of novel, potent bisphosphonates in two short-term rat
      models.
AB  - Bisphosphonates are used clinically to inhibit bone resorption but they may also
      cause renal damage. For the profiling of new potent bisphosphonates, their
      adverse renal effects were investigated in 2 rat models. In the first model,
      bisphosphonate was repeatedly injected (1 mg/kg, subcutaneously) over 2 weeks and
      the urinary excretion of malate dehydrogenase was monitored to assess nephrotoxic
      potential. Of the 6 new compounds tested, 3 markedly elevated malate
      dehydrogenase whereas 3 others caused only minor changes similar to those
      observed with 6 reference bisphosphonates that are already used clinically. On
      the basis of a therapeutic index (inhibition of bone resorption versus renal
      effects) 7-180 fold greater than that of other analogues, the compound CGP 42446
      was further profiled. In the second model, CGP 42446 or pamidronate was infused
      (1.5-50 mg/kg, intravenously) into anaesthetized rats and the serum urea
      concentration was monitored as an indicator of renal dysfunction. Both compounds
      elevated serum urea in a time- and dose-dependent manner, but the ED100 value for
      CGP 42446 was 3.8-fold higher than that of pamidronate. It is concluded that CGP
      42446 (zoledronate) has a low nephrotoxic potential and can be further developed
      as a new potent inhibitor of bone resorption.

PMID- 9181600
TI  - Effects of mercuric chloride and methyl mercury on cholinergic neuromuscular
      transmission in the guinea-pig ileum.
AB  - The effects of mercuric chloride (HgCl2) and methyl mercury (MeHg) were examined
      on basal mechanical activity and electrically-induced neurogenic cholinergic
      contractions (twitch contractions) in longitudinal muscle-myenteric plexus strips
      from guinea-pig distal ileum. Both compounds at 0.33 microM slightly enhanced the
      amplitude of twitch contractions in approximately 50% preparations. This effect
      was probably due to facilitation of acetylcholine (ACh) release since 0.1 and 1
      microM mercurials increased electrically-evoked tritium outflow from [3H]choline
      preloaded muscle layer with attached myenteric plexus. Conversely, higher mercury
      concentrations inhibited twitch contractions (HgCl2 IC50 = 21.3 +/- 6.4 microM;
      MeHg IC50 = 45.1 +/- 5.5 microM), as well as contractions to exogenous ACh (0.1
      microM) in resting preparations, and concomitantly increased the basal tone. The
      former effects possibly reflected an antimuscarinic activity of mercury, while
      the latter was related to alterations of calcium homeostasis in the effector
      cells. Indeed, the effect of HgCl2 on basal tone was antagonized by the Ca2+
      entry blocker nifedipine (3, 10, 30 nM), indicating Hg-induced facilitation of
      Ca2+ influx through voltage-dependent channels. On the whole, our results suggest
      that cholinergic neuromuscular transmission and Ca(2+)-dependent mechanisms
      underlying smooth muscle contractility are targets for mercury toxicity in the
      intestine.

PMID- 9181603
TI  - Carbonyl reduction of daunorubicin in rabbit liver and heart.
AB  - A major problem of anthracycline anticancer treatment are the cardiotoxic side
      effects associated with drug therapy. Increased attention has recently been
      focused on the 13-hydroxy anthracycline metabolites which are formed by carbonyl
      reduction of the parent drug as contributing to cardiotoxicity. By using
      daunorubicin as a reference molecule, our study was designed to quantitatively
      evaluate and compare the extent of anthracycline carbonyl reduction of liver and
      heart at the physiological important pH 7.4, and to identify the enzyme(s)
      involved under these conditions. The present kinetic data indicate that only one
      single enzyme system is active in cytosol of both tissues. According to its
      specific inhibition by quercitrin and the failure of a barbiturate to affect
      activity the enzyme responsible for daunorubicin carbonyl reduction in these
      fractions is carbonyl reductase (EC 1.1.1.184). Since the KM values differ
      significantly from each other, it is suggested that liver and heart express
      different isoforms of this enzyme. We failed to detect any specific daunorubicin
      carbonyl reductase activity in both microsomal fractions. Intrinsic clearance
      values revealed that liver has obviously 350-times the capacity of total 13
      hydroxy metabolite formation compared to heart. This indicates that under a
      therapeutic regimen 13-hydroxy anthracyclines of hepatic origin would add to the
      metabolites that are produced by the heart itself. The prevention of these
      metabolites may represent a potential approach for enhancing the safety and
      efficacy of anthracycline chemotherapy.

PMID- 9181602
TI  - Pharmacokinetics, toxicity, side effects, receptor affinities and in vitro
      radiosensitizing effects of the novel metoclopramide formulations, sensamide and
      neu-sensamide.
AB  - Metoclopramide is a drug which has experienced worldwide use in the clinic for
      over 30 years as an antiemetic. Recently, it has also been shown to possess radio
      and chemosensitizing properties in both animal tumour models and humans at the
      higher dose of 2 mg/kg. Two new metoclopramide formulations are being clinically
      developed and they differ mainly in whether the pH of their formulations are
      acidic (pH 2.5-3.5) or neutral (pH 6.5-7.0). Here we report that intramuscular
      administration of neutral metoclopramide is about 100% bioavailable, safer and
      with reduced side effects compared to acidic metoclopramide delivered by
      intramuscular injection to rats within the dose range of 3.5 to 14 mg/kg. The
      intramuscular administration of metoclopramide was also about 100% bioavailable
      compared to the intravenous route of administration. Furthermore, neutral
      metoclopramide had significantly decreased affinity for dopamine D2 receptors and
      increased affinity for 5-hydroxytryptamine, receptors, but the radiosensitizing
      potency was the same, when compared to equimolar concentrations of acidic
      metoclopramide. Taken together these data support the continued development of
      neutral metoclopramide for high dose intramuscular administration of
      metoclopramide for future clinical use as both an antiemetic and radiosensitizer.

PMID- 9181604
TI  - Bioavailability of enrofloxacin after oral administration to fed and fasted pigs.
AB  - The disposition of enrofloxacin was measured after intravenous and oral
      administration to pigs. Eight clinically healthy pigs weighing 25 to 40 kg
      received a dose of 5 mg/kg intravenously and 10 mg/kg orally in both a fasted and
      a fed condition in a three-way cross-over design. Enrofloxacin was present in
      plasma for up to 72 hr after both intravenous and oral administration to fasted
      as well as fed pigs. The steady state volume of distribution was determined to
      3.9 +/- 0.5 1/kg body weight which indicates that enrofloxacin was widely
      distributed in the body. The bioavailability was determined to 83 +/- 13% in fed
      and to 101 +/- 32% in fasted pigs. Based on the bioavailability and the resulting
      plasma concentrations it is concluded that a therapeutically active concentration
      for the most common porcine microbial pathogens are maintained for at least 24 hr
      after oral administration of 10 mg/kg body weight to fasted as well as to fed
      pigs. Ciprofloxacin which is an active metabolite of enrofloxacin was observed in
      plasma samples from all treated pigs, but the concentration never exceeded 0.1
      microgram/ml. During the first 24 hr after the administration of enrofloxacin the
      concentration of the metabolite made up less than 10% of the corresponding
      concentration of the parent compound.

PMID- 9181605
TI  - Effect of pretreatment with felbamate on toxicity of soman in mice.

PMID- 9181606
TI  - Photoaugmentation effects demonstrated in vitro.
AB  - A number of sulphonamide-derived oral antidiabetics and diuretics were
      investigated for phototoxic properties, using different sources of light, by
      means of a photohemolysis test. Photohemolysis was obtained after irradiation
      with UVA, visible light and solar simulating irradiation. No phototoxic
      properties were seen when the test samples were exposed to UVB alone. The most
      prominent hemolysis was induced by solar simulating irradiation. When exposing
      the the test samples to UVB prior to the subsequently applied UVA, visible light
      or solar simulating irradiation, a significantly higher hemolysis was detected
      compared with the previous tests, suggesting photoaugmentation effects in this
      model.

PMID- 9181607
TI  - Effects of near-infrared radiation on the epidermal proliferation and cutaneous
      immune function in mice.
AB  - While ultraviolet radiation alters various cutaneous cell functions, little is
      known about the photobiological effects of infrared radiation (IR) on the skin
      except its local thermal effect. This study demonstrated that single exposure of
      mouse skin to near IR (0.7-1.3 microns) reversibly suppressed the proliferating
      activity of the epidermis, the density of Langerhans cells, and the ability of
      skin to induce contact hypersensitivity reaction. During the exposure, the ear
      surface temperature was elevated from a mean of 27 to 31.2 degrees C. The results
      suggest that near IR can modulate the epidermal proliferation and part of the
      skin immune system, with a mild thermal effect.

PMID- 9181608
TI  - Effects of low concentrations of cis- and trans-urocanic acid on cytokine
      elaboration by keratinocytes.
AB  - The urocanic acid cis isomer (cis-UCA) is a possible cutaneous photoreceptor for
      the immunomodulatory phenomena that follow ultraviolet B irradiation. Several
      experiments in animals show an inhibitory action of cis-UCA on cellular immunity.
      However, the action of cis-UCA on the synthesis of cytokines in keratinocytes
      remains unknown. Long-term cultures of normal human keratiocytes were prepared in
      a serum-free medium, and stimulated with 1 microgram/ml of phorbol 12-myristate
      13-acetate (TPA) and UCA or UVB-UCA (10-100 micrograms/ml). Synthesis of the
      following cytokines was measured using ELISA and Northern blot techniques: TNF
      alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TGF-beta 1. TPA increased TNF-alpha
      protein levels in culture supernatants. No changes in Il-1 alpha and IL-1 beta
      protein levels were detected in basal culture supernatant after TPA stimulus. TPA
      augmented RNA expression for TNF-alpha, IL-1 alpha, IL-1 beta and TGF-beta 1. UCA
      isomers did not induce cytokine changes in protein synthesis. Expression of IL-1
      alpha and IL-1 beta genes was increased after exposure to 100 micrograms/ml UVB
      UCA (70 micrograms/ml cis-UCA). A slight increase in TNF-alpha RNA expression was
      detected when the dose of UVB-UCA reached 100 micrograms/ml. No effects on
      cytokine synthesis were found after UCA stimulus. These results suggest that low
      doses of cis-UCA do not effect cytokine synthesis by keratinocytes.

PMID- 9181609
TI  - Variation in toe-web response of turkey poults to phytohemagglutinin-P and their
      resistance to Escherichia coli challenge.
AB  - One thousand 5-wk-old male turkeys from each of two commercial strains (A and B)
      were grouped into low, medium, and high responders based on the cutaneous
      basophil hypersensitivity (CBH) response obtained 24 h after toe-web inoculation
      with 100 micrograms of phytohemagglutinin-P (PHA-P). The CBH response for Strain
      A was higher than strain B (P = 0.00001) and ranged from 0 to 1.95 mm, with a
      mean of 0.66, whereas the CBH response for Strain B ranged from 0 to 1.67 mm with
      a mean of 0.38. At 6 wk of age, 36 birds from each of the six response groups
      were inoculated into the left thoracic air sac with 1.5 x 10(7) cfu of an early
      log phase broth culture of Escherichia coli. Samples of 5 or 10 birds were
      necropsied from each of the six groups at 7, 14, 28, and 42 d postinfection (PI).
      Birds were scored for air-sacculitis/pericarditis (AS) and turkey osteomyelitis
      complex (TOC). Overall mortality of birds inoculated with E. coli was 31%. There
      were no mortalities in unchallenged controls. Strain A had significantly higher
      Week 1 mortality, marginally higher overall mortality (P = 0.1), and higher AS
      scores than Strain B. There were no TOC lesions detected until 7 d PI, after
      which all mortalities had TOC lesions in multiple sites. The differences in CBH
      response within each strain were not clearly correlated to E. coli
      susceptibility. However, these data suggest that air sac inoculation of E. coli
      can provide a useful model for the study of TOC. The greater incidence of disease
      in Strain A indicates that an enhanced inflammatory response may increase
      susceptibility to E. coli septicemia.

PMID- 9181610
TI  - Assessing the sensitivity of egg yolk antibody testing for detecting Salmonella
      enteritidis infections in laying hens.
AB  - The identification of infected commercial poultry flocks has become a pivotal
      component of efforts to reduce the incidence of egg-associated transmission of
      Salmonella enteritidis to humans. To assess the sensitivity with which testing
      for specific antibodies in egg yolks can be applied to detect S. enteritidis
      infection in laying chickens, groups of hens were orally inoculated with either
      10(3), 10(5), or 10(7) cfu of a phage type 13a strain of S. enteritidis. Eggs
      from these hens were collected for 4 wk after inoculation and yolk samples were
      tested for antibodies to S. enteritidis flagella by ELISA. All hens that were
      inoculated with 10(7) cfu of S. enteritidis were detected as infected by the egg
      yolk ELISA when eggs were tested individually, as were up to 66 and 35% of hens
      inoculated with 10(5) or 10(3) cfu, respectively. Even when yolks from infected
      hens were diluted 1:10 in yolk from uninfected hens, specific antibodies could
      still be found in eggs from 31% of hens given 10(7) cfu of S. enteritidis and 13%
      of hens given 10(3) cfu. These results demonstrate that egg yolk antibody testing
      can provide a highly sensitive indication of prior exposure to S. enteritidis,
      and should accordingly be useful for verifying the effectiveness of programs
      designed to reduce the incidence of S. enteritidis infection in poultry.

PMID- 9181611
TI  - Effect of betaine on the growth performance of chicks inoculated with mixed
      cultures of avian Eimeria species and on invasion and development of Eimeria
      tenella and Eimeria acervulina in vitro and in vivo.
AB  - At 7 d postinoculation (DPI) with a mixed culture of avian Eimeria species, 21-d
      old chicks maintained in batteries and floor pens on a diet containing 0.15% (3
      lb/ton) betaine plus 66 ppm (60 g/ton) salinomycin were significantly heavier and
      had significantly lower feed conversion ratios and mortality than chicks fed
      diets containing 0.15% betaine or 66 ppm salinomycin alone, or the control diet.
      At 31 DPI, when the chicks were 45 d old, the differences between the diet groups
      were not as great as at 7 DPI. In vitro, except at high concentrations, betaine
      was nontoxic to sporozoites of Eimeria tenella or Eimeria acervulina and had
      little effect on their invasion and development in cultured cells. In vivo,
      invasion by E. tenella and E. acervulina sporozoites was significantly reduced in
      all chicks fed diets containing betaine or salinomycin compared with that in
      control chicks. There was a significant interaction between betaine and
      salinomycin that impacted on invasion by both species. Overall development of E.
      tenella did not appear to be adversely affected by addition of betaine to diets
      containing salinomycin. Conversely, development of E. acervulina was reduced in
      chicks fed diets containing 0.075% (1.5 lb/ton) betaine plus 66 ppm salinomycin
      as compared with that in chicks fed salinomycin alone.

PMID- 9181612
TI  - Nitric oxide production during Eimeria tenella infections in chickens.
AB  - The objective of this study was to gather evidence for production of nitric oxide
      (NO) during a primary infection with the protozoan parasite Eimeria tenella,
      which carries out its life cycle in the ceca of chickens. Relationships of plasma
      levels of NO2(-)+NO3-, stable metabolites of NO, with parasite dose and with time
      after infection were examined, as well as effects of administration of
      aminoguanidine, an inhibitor of induced nitric oxide synthase (iNOS). Inoculation
      with 5 x 10(4) and 1 x 10(6) but not 1 x 10(3) oocysts per chick caused
      significant (P < or = 0.05) increases in micromolar concentrations of plasma NO3(
      )+NO3- when measured at 7 d postinoculation (PI). In chickens inoculated with 5 x
      10(4) oocysts, significant (P < or = 0.05) increases in plasma NO2(-)+NO3- were
      seen at 5 and 7 but not 3 d PI. Daily intraperitoneal administration of 1.25 mg
      per chick aminoguanidine during the period of infection did not lower the
      increases in plasma NO2(-)+NO3- seen at 5 and 7 d PI, and did not affect the
      degree of colonization of the cecal tissue by the parasite. However,
      administration of aminoguanidine did alter the gross appearance of the ceca,
      which were less swollen and filled with blood at 5 and 7 d PI as compared with
      ceca from untreated chickens. Hemorrhage is a major pathological manifestation of
      E. tenella infections, associated with the disruption of the cecal mucosa by the
      developing parasite. The results of this experiment are consistent with the
      hypothesis that an aminoguanidine-inhibitable NO synthase, perhaps in the
      vascular endothelium of the cecal blood vessels, may contribute to hemorrhage by
      causing vasodilation.

PMID- 9181613
TI  - Production of free radical species during Eimeria maxima infections in chickens.
AB  - Five experiments were conducted to investigate the production of nitric oxide
      (NO) and superoxide anion (O2-) during infections of chickens with the coccidial
      parasite, Eimeria maxima, in order to assess the importance of these free radical
      species in the pathogenesis of the infections. Nitric oxide production was
      estimated by analyzing NO2(-)+NO3-, stable metabolites of NO, in the plasma and
      intestinal mucosa. The potential for O2- production was estimated from activities
      of beta-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in mucosal
      homogenates. Levels of NO2(-)+NO3- reached maximum values at about 6 d
      postinoculation, a time when mucosal damage was high and oocysts were being shed.
      The activity of NADPH oxidase in infected mucosa was also increased. Thus, at
      that time, there was a potential for oxidative destruction of mucosal tissue from
      these free radicals and their reaction products. Levels of NO2(-)+NO3- did not
      increase in a stepwise manner with increasing infective dose, suggesting that
      production of NO may be regulated post-transcriptionally by other factors
      elaborated by the immune response to infection, or may be controlled by substrate
      limitations. A comparison of two E. maxima strains indicated that the virulence
      of a strain was not directly related to NO production. Increased production of O2
      due to increased NADPH oxidase activity during infection may cause a reduction
      in levels of carotenoid pigments that is unrelated to malabsorption.

PMID- 9181614
TI  - Interaction of dietary flaxseed with coccidia infections in chickens.
AB  - Two experiments were conducted to determine effects of diets containing n-3 fatty
      acids (n-3FA) from whole as well as ground flaxseed on the performance of
      broilers during coccidia infections. Diets were fed from 1 d of age through 3 wk
      of age. Chickens were infected with coccidia at 2 wk of age and the effects of
      infection assessed at 6 d postinfection. The first experiment contrasted effects
      of several high n-3FA-containing diets, including one supplemented with whole
      flaxseed, on infections with Eimeria tenella or Eimeria maxima. Infected chickens
      that consumed the flaxseed-supplemented diet had the lowest weight gains, but
      they were not significantly different from gains of infected chickens on the
      control diet. Diets supplemented with 5% menhaden oil or 15% flaxseed
      significantly reduced lesions caused by E. tenella, but had no effect on lesions
      caused by E. maxima. In a second experiment, diets supplemented with 5 or 10%
      ground flaxseed were assessed for effects on the performance of broilers infected
      with three dose levels (500, 5,000, or 50,000 oocysts) of E. maxima. Neither
      flaxseed diet protected weight gain during infection with 50,000 oocysts.
      However, a 5% flax diet protected weight gains in chickens infected with 500 or
      5,000 oocysts. Diets supplemented with 5 or 10% ground flaxseed exacerbated
      lesions in chickens infected with 5,000 or 50,000 E. maxima oocysts compared to
      the control diet. Thus, diets containing high amounts of n-3 fatty acids do not
      affect the development of all Eimeria sp. in the same manner. The oxidative
      stress produced by these diets may more adversely affect development of E.
      tenella, which infects the relatively oxygen-poor ceca, whereas it does not
      affect development of E. maxima which parasitizes the middle portion of the small
      intestine.

PMID- 9181616
TI  - Energy evaluation of eight barley cultivars for poultry: effect of dietary enzyme
      addition.
AB  - Three experiments were conducted to study eight barley cultivars and the effect
      of enzyme addition on their energy value for poultry. In Experiment 1, the AMEn
      of a reference barley (Beka cultivar) was calculated by increasing barley
      concentrations (30, 40, 50, and 60%) that replaced a high protein basal diet. In
      Experiment 2, eight barley cultivars (four spring and four winter cultivars)
      replaced the reference barley in the diet with 50% barley inclusion. Two of the
      winter cultivars were two-rowed and two were six-rowed cultivars. A commercial
      enzyme was added to these diets to study the effect of enzyme addition. Diets
      were consumed ad libitum by 27 and 145 21-d-old Arbor Acres broiler chicks, in
      Experiments 1 and 2, respectively. In Experiment 3, 66 adult roosters were used
      to determine the TMEn of the eight cultivars used in Experiment 2. Dietary AMEn
      decreased linearly (P < 0.05) with increasing barley (Beka cultivar) inclusion.
      Beka barley AMEn was calculated by extrapolation of the linear regression
      equation be equal to 2,980 kcal/kg DM. Barley energy value was influenced by
      cultivar (P < 0.001); the spring cultivars showed greater energy value than the
      winter cultivars (2,963 vs 2,852 kcal AMEn/kg DM; 3,192 vs 2,929 kcal TMEn/kg
      DM). Two-rowed cultivars showed higher TMEn than six-rowed winter cultivars,
      although no differences were found for AMEn. The correlation between AMEn and
      TMEn values of barley was relatively low (r = 0.69); therefore, barley TMEn
      cannot be extrapolated to AMEn for young chicks. Enzyme addition produced an
      average increase of 220 kcal/kg DM in barley AMEn (P < 0.001); there was a
      significant (P < 0.10) interaction between barley cultivar and enzyme
      supplementation. The increment of barley AMEn caused by enzyme addition was
      partly explained (47%) by an increase in barley viscosity. This relationship
      implies that enzyme supplementation significantly improves the feeding value of
      high as compared to low viscosity barley samples, which involved a decrease in
      AMEn variation among cultivars for enzyme-supplemented barley. No relationship
      was found between AMEn of unsupplemented barley cultivars and their chemical
      composition. Instead, a relationship was detected for enzyme-supplemented barley;
      therefore two equations were proposed for predicting the AMEn of enzyme
      supplemented barley to be used directly in diet formulation.

PMID- 9181615
TI  - Changes in fatty acid profiles in different lipid classes during late development
      of turkey embryos from two genetic lines.
AB  - Fatty acid (FA) profiles in embryonic yolk sacs (YS) and livers were studied in
      embryos from a randombred turkey line (RBC2) and a line selected for body weight
      at 16 wk (F line). There were no differences in FA profiles of fresh yolk lipids.
      During the course of incubation, oleic acid (C18:1) was higher and linoleic acid
      (C18:2) was lower in YS triglyceride (TG) and phospholipid (PL) subclasses in F
      line compared with RBC2 embryos. In both lines, the C18:1 content of YS
      cholesteryl esters (CE) increased from 58 to 63% during the last 6 d of
      incubation. From 22 to 28 d of incubation, there was a constant C18:1
      concentration in hepatic CE, which was > 60% of total hepatic CE FA. As
      incubation proceeded, palmitic acid (C16:0) and C18:1 in hepatic TG decreased
      from 27 to 16% and 37 to 34%, respectively. The stearic acid (C18:0) in TG
      increased from 12% at Day 22 to 32% of total FA at hatch (Day 28) in RBC2 embryos
      compared with a lesser increase in the F line (11.8 to 18.6%). In hepatic PL,
      arachidonic acid (C20:4) decreased, whereas both C16:0 and C18:0 increased from
      22 to 28 d of incubation. During this same time period, there was an overall
      decline in docosahexaenoic acid (C22:6) only in the RBC2. On Days 26 and 28, F
      line embryos had greater concentrations of C22:6 and C20:4 in hepatic PL than did
      RBC2. These results suggest that selection for increased BW has changed the
      proportional incorporation of different FA into embryonic lipids.

PMID- 9181617
TI  - Protein quality and calcium availability from extruded and autoclaved turkey
      hatchery residue.
AB  - The protein quality of an extruded mixture of hatchery by-product meal and
      soybean meal (EHSM) and the calcium availability of autoclaved hatchery by
      product meal (AHBM) were determined. In Experiments 1 and 2, EHSM or soybean meal
      (SBM) were the only protein sources in diets formulated to contain 16, 20, or 24%
      CP. In both experiments, there were five or six replicate pens randomly allotted
      to each level of dietary protein and each pen contained five poults. In
      Experiment 1, there was a significant increase in the Protein Efficiency Ratio
      (PER; P < or = 0.005) in poults from a fast-growing line compared with poults
      from a slow-growing line selected for egg production but no significant
      differences between EHSM and SBM. In Experiment 2, PER was increased in poults
      fed EHSM (P < or = 0.002). In both studies, there was a large decline in PER in
      those poults fed the 16% SBM diet, and this resulted in a significant source by
      level interaction. There were no significant source or level of protein effects
      on the Net Protein Ratio (NPR) or Net Protein Utilization (NPU) in Experiment 2.
      In Experiment 3, AHBM, steamed bone meal and limestone were the primary sources
      of calcium in diets containing 0.6, 0.8, 1.0, and 1.2% calcium. There were four
      replicate pens per level and source of calcium. The length and width of the femur
      and tibia were measured along with fat-extracted bone weight and ash. Poults fed
      diets containing AHBM and limestone had improved feed efficiency (P < or = 0.008)
      compared with those fed bone meal. There were no significant diet effects on any
      bone measurements.

PMID- 9181618
TI  - The bioefficacy of zinc bacitracin in practical diets for broilers and laying
      hens.
AB  - Two balance trials were conducted to examine the response in metabolizable energy
      and metabolizability of both fat and amino acids to graded levels of zinc
      bacitracin (ZnB; Albac registered trade name of Alpharma, Oslo, Norway) in
      practical broiler and layer diets varying in their nutrient density. Broiler
      diets were supplemented with either 0, 20, or 50 mg ZnB/kg and layer diets were
      supplemented with either 0, 50, or 100 mg ZnB/kg. Each experimental diet was fed
      to five replicates of four broiler chicks each or nine replicates of individually
      housed laying hens, respectively. All balance parameters were significantly
      influenced by nutrient density, age, and dietary ZnB level. No significant
      interactions between ZnB by nutrient density were found. Addition of ZnB resulted
      in a lower excreta:feed ratio and an improved N retention; there was a nearly
      linear relationship between these effects and dietary ZnB levels. Moreover,
      dietary MEn content was linearly enhanced by ZnB supplementation. As a
      consequence, the bioefficacy of ZnB can be expressed in terms of MEn units: the
      average MEn equivalency of ZnB was 2,080 and 1,184 Mcal/kg, for broiler chicks
      and laying hens, respectively.

PMID- 9181620
TI  - The effect of thermal processing and enzyme treatments of soybean meal on growth
      performance, ileal nutrient digestibilities, and chyme characteristics in broiler
      chicks.
AB  - Effects of thermal processing (toasting or extrusion) of untoasted soybean meal
      on growth performance, apparent ileal nutrient digestibilities, and chyme
      characteristics were studied in broiler chicks fed diets with soybean meal as the
      main protein source. Effects of increasing shear forces during extrusion as well
      as enzyme treatments (protease and carbohydrase) were also studied. When compared
      with toasting, extrusion significantly improved feed conversion ratio (1.56 vs
      1.62) and apparent ileal digestibilities of CP and nonstarch polysaccharides
      (87.5 vs 82.2% and 26.7 vs 11.4%, respectively). Enzyme treatment improved
      apparent ileal digestibility of CP and nonstarch polysaccharide compared with no
      enzyme treatment (85.2 vs 83.7% and 20.6 vs 14.5%, respectively); however, enzyme
      treatments did not result in a better growth performance of the chicks. Among the
      enzyme treatments, no differences were found in growth performance and apparent
      ileal CP digestibility, whereas the carbohydrase significantly improved apparent
      ileal nonstarch polysaccharide digestibility compared with the other enzyme
      treatments. Extrusion of SBM at the highest shear level caused a significant
      increase in the water-holding capacity, chyme viscosity, and concentration of
      soluble nonstarch polysaccharides in the chyme compared with extrusion of SBM at
      lower shear levels. The increase in chyme viscosity did not affect growth
      performance, nor did it influence apparent ileal nutrient digestibilities.

PMID- 9181619
TI  - Effect of high ambient temperature on feed digestibility in broilers.
AB  - The effect of chronic heat exposure on feed digestibility of broilers was
      investigated. Eighty 4-wk-old male chickens were brooded in individual battery
      cages in two controlled-environment rooms at a constant ambient temperature (22
      or 32 C) until 6 wk of age. They were equally distributed into three treatments:
      22 C, ad libitum feed consumption (22AL); 32 C, ad libitum feed consumption
      (32AL), and 22 C, pair-feeding on the daily feed intake of heat-exposed chickens
      (22PF). Broilers were fed either a standard corn-soybean meal diet (control diet)
      or a practical seasonal diet containing several ingredients including wheat,
      spring pea, and animal fat (summer diet). Digestibility of energy, dry matter,
      protein, fat, starch, and nitrogen, and total mineral balances were measured
      between 38 and 42 d of age. Apparent metabolizable energy content of summer diet
      was significantly decreased in 32AL compared to 22AL, whereas AME of the control
      diet did not change. Nitrogen retention was significantly reduced in 32AL birds
      compared to 22AL and 22PF birds, irrespective of the diet. Taking into account
      these differences in nitrogen balance, AMEn was reduced under hot exposure: -72
      and -155 kcal for control and summer diets respectively, in 32AL compared to 22PF
      chickens. This reduction could be explained by a significant decrease of nutrient
      digestibility:protein: -4.2 percentage units irrespective of the diet, fat: -1.7
      and -5.2 percentage units for control and summer diets respectively, and starch: 
      4.2 percentage units for summer diet. It thus appears worthwhile to take into
      account such reduction in digestibility to formulate practical diets for brooding
      under hot conditions. High quality oil and protein sources should also be used
      instead of low quality feedstuffs, like animal sources, in such conditions.

PMID- 9181621
TI  - Digestible sulfur amino acid requirement of starting turkeys.
AB  - Three experiments (a total of 1,020 poults) were conducted to determine the
      digestible sulfur amino acid (SAA) requirement for female turkey poults during
      the starter period. Poults were fed a standard corn-soybean meal diet (PC) that
      met or exceeded NRC recommendations (28% CP, 3,172 kcal MEn/kg) for 1 wk and were
      then randomly assigned to treatments until 22 d (Experiment 2 and 3) or 23 d
      (Experiment 1) of age. Dietary treatments included the PC diet and seven or nine
      titrated levels of methionine added to a basal corn-soybean meal diet, for a
      total of 0.50 to 1.33% total digestible SAA. The basal diet contained 18.4%
      intact crude protein. All diets contained 3,171 kcal MEn/kg. The true digestible
      SAA content of the basal diet without methionine additions was 0.50% based on
      digestibility assays of the corn and soybeans with cecectomized turkeys. Diets
      were formulated to contain 1.40% digestible lysine. Other amino acids were
      maintained at levels in relation to lysine based on previous research with
      turkeys and the Illinois Ideal Chick Protein. Broken-line analysis suggests that
      the digestible SAA requirement for female turkeys during the starter period is
      0.76% for optimum body weight gain and 0.75% for optimal feed:gain at the energy
      levels used in these studies.

PMID- 9181622
TI  - Decorin and collagen type I gene expression in avian low score normal pectoral
      muscle.
AB  - The avian Low Score Normal (LSN) genetic muscle weakness is phenotypically
      characterized by a reduction in the ability of the birds to right themselves from
      a supine position. Compared to normal skeletal muscle, LSN muscle has normal
      myosin isoform switching and cell-cell recognition, elevated glycosaminoglycan
      and decorin levels at embryonic Day 20, and a large increase in collagen
      crosslinking at 6 wk posthatch. To begin to determine the biological mechanism
      involved in the elevated decorin protein concentration at embryonic Day 20, the
      steady-state levels of transcripts encoding both decorin and collagen Type I at
      embryonic Days 14, 19, and 20, and at 1 d and 6 wk posthatch were measured. On
      embryonic Day 20, collagen Type I transcripts were not different from the control
      but there was a significant elevation in decorin transcript levels. At 1 d and 6
      wk posthatch, transcript levels of decorin and collagen Type I were not different
      between LSN and controls. The change in decorin transcript steady-state levels is
      limited to late embryonic development and suggests an alteration in a signal
      transduction pathway regulating decorin transcription.

PMID- 9181624
TI  - Supplemental thyroid hormones and molting in turkey breeder hens.
AB  - The objective of the current study was to determine whether thyroid physiology
      may affect molting time in turkeys. Two trials using approximately 144 hens were
      conducted to elucidate thyroidal factors that limit the molting process. Thyroid
      hormones or a thyroid blocker (thiouracil) were given to the hens during a molt
      by supplementing the diet with thyroxine (T4), triiodothyronine (T3), or
      thiouracil. Supplementing with T4 reduced the number of days to return to egg
      production, whereas supplementing with thiouracil or T3 prolonged days to first
      egg. The observations support previous suggestions of separate functions for T3
      and T4 during molting. As had been observed many times previously, the feeding of
      thiouracil delayed the molt but did not completely stop the molting process. The
      hens fed thiouracil returned to 50% egg production nearly 10 d after the control
      group, whereas T3 prolonged the return to 50% egg production nearly 1 wk later.
      The data indicate the endogenous low levels of T4, but not T3 in modern strains
      of turkeys may contribute to a relatively longer molting period of turkey breeder
      hens induced to molt out of season.

PMID- 9181623
TI  - Transfection of avian LMH-2A hepatoma cells with cationic lipids.
AB  - LMH-2A is an estrogen-responsive avian hepatoma cell line whose susceptibility to
      cationic-lipid-mediated transfection is poorly described. 3 beta[N-N',N'
      dimethylaminoethane)-carbamoyl] cholesterol (DCC) requires a one-step synthesis,
      and can be used to formulate transfection-grade liposomes when combined with
      dioleoylphosphatidyl-ethanolamine (DOPE) 1/1 (wt/wt). Luciferase activities in
      LMH-2A cells were 8.5-fold and 87.5-fold greater than those in HepG2 and FTO2B
      cells, respectively, following DCC-liposome-mediated transfection with a reporter
      consisting of the human cytomegalovirus immediate-early promoter (CMV), joined to
      Photinus pyralis luciferase (L) cDNA, designated pCMVL. Using pCMVL, N-(2
      bromoethyl)-N,N-dimethyl-2,3-bis(9-octadecenyloxy)-propana minimun bromide)
      (BMOP)/DOPE 1/1 (wt/wt), at a 7.5:1 ratio with DNA, produced luciferase
      activities that were 2.9-fold higher than those of DCC-liposomes, at an optimal
      10:1 lipid:DNA ratio. At optimal lipid:DNA ratios, commercially available
      liposomes, Transfectam, Lipofectamine, and Lipofectin, produced luciferase
      activities that were 1.39, 1.03, and 0.47-fold those of DCC-liposomes. The effect
      of 0, 10, 100, or 500 nM/L 17 beta-estradiol on the expression of pCMVL and a
      second luciferase reporter containing the -593/+48 promoter region of the
      estrogen-responsive avian apo VLDL-II gene, designated pApoL, was tested in cells
      cultured in the presence or absence of 10% chicken serum. The CMV promoter
      supported a high level of expression in LMH-2A cells that was unaffected by serum
      alone, but was weakly responsive to estrogen. Estrogen responses of both
      reporters reached a plateau at 10 nM/L. Estrogen increased the expression of
      pApoL 24-fold and 79-fold in the absence and presence of serum, respectively. The
      -593/+48 region of the apo VLDL-II promoter may not contain previously reported
      negative insulin response elements, but chicken serum contains factors that
      enhance estrogen responsiveness of this region.

PMID- 9181625
TI  - Developmental changes in embryonic and extra-embryonic insulin-like growth factor
      I tissue concentrations in the turkey embryo.
AB  - The ontogeny of insulin-like growth factor-I (IGF-I) embryonic and extra
      embryonic tissue concentrations were determined in the developing turkey embryo.
      At 2-d intervals, starting on Day 6 of incubation, individual tissues (n = 8 for
      each stage of incubation) were removed, weighed, pulverized, and extracted in 1 M
      acetic acid for IGF-I determination. Amniotic and allantoic fluid were collected
      starting on Day 8, serum on Day 12, and analyzed for IGF-I levels. Serum IGF-I
      levels were the lowest on Days 12 and 28 of incubation (5.9 and 9.5 ng/mL),
      respectively, and the highest on Day 20 (16.2 ng/mL). Allantoic and amniotic
      fluid IGF-I concentrations were essentially unchanged during incubation. Extra
      embryonic tissue IGF-I levels increased in both the yolk sac and chorioallantoic
      membranes as incubation advanced with concentrations being 8- to 10-fold greater
      in the chorioallantois. Embryo tissue IGF-I concentrations varied greatly with
      regard to tissue and stage of development. Brain IGF-I levels were the highest on
      Day 8 and lowest on Day 26 (423 vs 35 pg/mg protein, respectively). Tissue IGF-I
      pattern in the heart mirrored that of brain. Liver IGF-I was low (< 40 pg/mg
      protein) from Day 10 to 20 and undetectable on Days 22 to 28. Muscle IGF-I levels
      were similar in the final days of development to those observed in early
      incubation. Bone IGF-I levels were highest in mid-incubation and lowest on Day
      26. Peptide levels in the gastrointestinal tract (GI) tract and gizzard were
      dissimilar in that IGF-I was elevated in the GI tract in early incubation and
      declined with advancing incubation, whereas gizzard IGF-I levels peaked in late
      incubation. It is apparent that tissue synthesis of IGF-I is differentially
      regulated within a given tissue and stage of incubation during embryogenesis in
      the turkey embryo.

PMID- 9181626
TI  - Comparison of embryos and chicks that developed as single individuals in double
      yolk eggs with those that developed in single yolk eggs.
AB  - Body weight and muscle characteristics of 18- to 20-d-old broiler strain embryos
      developing in double yolk eggs (DY) that contained one embryo and one infertile
      ovum were compared with embryos in single yolk eggs (SY). Similar comparisons
      were made in the posthatching period. In some DY eggs, the embryos were bathed in
      a watery yolk-like fluid with no distinct second yolk present (Type 1 embryo). In
      others, the second yolk was contained within the vitelline membrane and
      surrounded by a vascularized membrane (Type 2). These embryos were heavier than
      Type 1 or embryos in SY eggs by 20 d of incubation. Their Pectoralis
      superficialis were heavier and had significantly more protein and DNA. Chicks
      that hatched from the DY eggs were heavier than those that hatched from SY eggs
      and they had heavier P. superficialis through at least 14 d of age. Pectoralis
      superficialis myofibers of chicks from DY eggs had greater cross-sectional area
      than those from SY eggs. Myofibers in the Semimembranosus of 7- and 14 d-old
      chicks from DY eggs tended to be larger than those from SY eggs, but the
      differences were not significant. There was no difference in apparent myofiber
      number in the Semimembranosus of the two types of chicks. The difference in BW
      between the two types of chicks diminished over time, so that by 42 d of age they
      were virtually identical. In summary, a nutritionally enriched in ovo environment
      resulted in embryos and chicks with enhanced growth and muscle mass, but the
      effects of enrichment diminished during posthatching life and eventually
      disappeared.

PMID- 9181627
TI  - Microbiological quality of cooked chicken breasts containing commercially
      available shelf-life extenders.
AB  - Experiments were conducted to determine the effect of various shelf-life
      extenders on the aerobic plate counts (APC) of cooked chicken breast meat stored
      at refrigeration temperatures. Fresh chicken breast meat obtained from local
      grocers was injected with either 0.5, 1, 1.5, or 2% sodium lactate; 0.63, 1.25,
      1.88, or 2.51 g/kg of a liquid smoke flavoring; 0.33, 0.66, 1, or 1.33% Per/Lac
      1901, a fermented whey product; or 0.25, 0.5, 0.75, or 1% Alta 2341, a fermented
      corn syrup product. The samples were cooked at 85 C dry bulb, 77.8 C wet bulb to
      an internal temperature of 76.7 C. The cooked chicken breasts were cut into 20-g
      samples and aseptically placed into Ziploc bags. Initial APC were enumerated
      following 2-d incubation at 30 C. Additional stored samples (2 C) were
      subsequently evaluated for APC every week for 5 wk. Only one of the four
      ingredients, Alta 2341, significantly extended cooked breast meat shelf-life over
      that of the controls. Using Alta 2341 would be beneficial in extending the
      refrigerated shelf-life of cooked chicken breast meat up to 5 wk.

PMID- 9181628
TI  - Effect of egg size and strain and age of hens on the solids content of chicken
      eggs.
AB  - A study was conducted to determine the effect of egg size and the age and strain
      of hens on the content of egg solids. Eggs were obtained from commercial farms
      from four strains of hens with similar age groups and received diets formulated
      to contain the same dietary energy and protein levels across the strains within a
      farm. Eggs were collected on 2 different d when the flocks reached the average
      ages of 28, 55, 75, and 97 wk. The eggs collected form each farm were pooled and
      sorted by size. Each individual egg was used as a replicate for yolk:white ratio;
      however, five yolks, five whites, and five whole eggs from each strain at each
      age period were pooled, homogenized, and then used as a replicate to determine
      the solids contents of yolk, white, and whole eggs. The yolk:white ratio of eggs
      from 28-wk-old hens was the lowest, that from 55- and 78-wk-old hens was the
      highest, and that from 97-wk-old hens was intermediate; however, the solids
      content (percentage) of whole eggs increased with the age of the hens. The solids
      content of egg white was highest in eggs from 28-wk-old hens. The white solids
      content of extra large eggs was greater than that of medium eggs, and yolk solids
      increased with egg size; however, the solids of whole egg were not affected by
      egg size. The strain of hens had a significant effect on the solids of whole egg,
      white, and yolk; however, the strain effect on yolk:white ratio was not
      significant. The results showed that young (28-wk-old) and old birds (97-wk-old)
      produced eggs with low solids content and intermediate aged hens (55- to 78-wk
      old) produced eggs with high solids content. Therefore, it may be more beneficial
      for egg producers and processors to use young (28-wk-old) and old birds (97-wk
      old) for table egg production and birds of intermediate age (55- to 78-wk-old)
      for liquid egg production.

PMID- 9181629
TI  - Food-deprivation increases cocaine-induced conditioned place preference and
      locomotor activity in rats.
AB  - Food-deprivation increases the reinforcing efficacy of cocaine and other drugs
      within self-administration experiments. In this study, the effects of food
      deprivation on cocaine-induced conditioned place preference were investigated.
      Male Sprague-Dawley rats were assigned to one of two feeding conditions: satiated
      (with ad libitum food) or deprived (maintained at 80% of free-feeding body
      weights). During conditioning trials, on alternate days, rats received IP
      injections of cocaine (0.0, 2.5, 5.0, or 10.0 mg/kg; n = 12 per dose group) and
      were confined for 30 min in one of two distinct environments. On intervening
      days, the same rats were injected with saline and confined for 30 min in the
      opposite environment. After four cocaine and four saline trails, a 15-min choice
      test (with no injections) was given. During this time, the rats were able to move
      freely through a passageway between both environments. Relative to the food
      satiated rats, the food-deprived rats showed a greater conditioned preference for
      the cocaine-paired environment during the choice test, greater cocaine-induced
      locomotor activity during conditioning trials, and a greater degree of
      sensitization to the activating effects of cocaine across conditioning trials.
      This study extends the general findings of food deprivation-induced increases in
      the reinforcing efficacy of cocaine to include the conditioned place preference
      paradigm.

PMID- 9181630
TI  - Trazodone and triazolam: acute subject-rated and performance-impairing effects in
      healthy volunteers.
AB  - The present study compared the acute subject-rated and performance-impairing
      effects of trazodone and triazolam in seven healthy humans. Trazodone (50, 100
      and 200 mg), triazolam (0.125, 0.25, 0.50 mg) and placebo were administered
      orally in a double-blind, crossover design. Drug effects were measured
      approximately 30 min before drug administration and repeatedly afterwards for 6
      h. Trazodone and triazolam produced dose-related increases in subject-ratings of
      drug effect and sedation. The absolute magnitude of trazodone's and triazolam's
      effects was comparable across these measures, which suggests the doses tested
      were equivalent on some behavioral dimension. By contrast, triazolam, but not
      trazodone, increased subject ratings of "dizzy", "excited", "nervous",
      "restless", "stomach turning" and "itchy skin". Triazolam, but not trazodone,
      significantly impaired learning, recall and performance. The present findings
      suggest trazodone may be a viable alternative to benzodiazepine hypnotics like
      triazolam, especially when needing to minimize drug-induced impairment. Future
      research could extend the present findings by replicating them in a clinically
      relevant population such as individuals with histories of drug abuse.

PMID- 9181631
TI  - Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed
      patients.
AB  - Little information exists on the concentrations of antidepressants and their
      metabolites in CSF. We measured plasma and CSF levels of trans-doxepin (trans
      DOX) and DOX metabolites in 12 depressed patients treated with DOX (250 mg/day)
      for 6 days. Spinal taps and blood samples were taken on day 7, 10 h after drug
      administration. Trans-DOX, cis-desmethyldoxepin (cis-DM-DOX), trans
      desmethyldoxepin (trans-DM-DOX) and di-desmethyldoxepin (DDM-DOX) were analyzed
      in CSF and plasma samples by HPLC with column-switching. Although DOX was given
      as a mixture of 85% trans-DOX and 15% of the pharmacologically more active cis
      DOX, we found similar amounts of cis-DM-DOX and trans-DM-DOX in plasma (59.8 +/-
      45.1 versus 72.0 +/- 60.0 ng/ml; NS), suggesting that isomerization of DOX had
      taken place. Trans-DOX and DOX metabolites could be detected in CSF of most
      patients. Relatively low CSF concentrations of the active metabolite cis-DM-DOX
      were measured. Clinical efficacy, as assessed by HAMD scores, was not
      significantly related to plasma or CSF concentrations of trans-DOX or its
      metabolites. Trans-DOX and DOX metabolites were distributed differently between
      plasma and CSF. It is concluded that isomerization of DOX is not only relevant
      for neuronal uptake inhibition, but also for the transport of the metabolites.

PMID- 9181632
TI  - Post-weaning housing conditions influence the behavioural effects of cocaine and
      d-amphetamine.
AB  - Post-weaning social isolation can induce profound and long lasting effects on an
      animal's behaviour. The present study investigated the influence of post-weaning
      housing conditions on the sensitivity of rats to the behavioural effects of d
      amphetamine and cocaine. The locomotor stimulant effects of both drugs were
      compared following acute and chronic administration. The influence of post
      weaning housing conditions on the effects of d-amphetamine and cocaine on
      responding for food and for a conditioned reinforcer were also examined. Isolated
      rats showed enhanced locomotor activity on exposure to a novel environment. This
      difference was further exaggerated following administration of d-amphetamine (0.5
      mg/kg) and cocaine (5 mg/kg). Isolated, but not enriched, rats exhibited
      sensitisation to the locomotor activating effects of repeated administration of a
      dose of 0.5 mg/kg d-amphetamine, whilst both groups sensitised equally to a dose
      of 1.0 mg/kg d-amphetamine. Rearing conditions did not affect sensitisation to
      cocaine (5, 10 mg/kg). Isolated rats exhibited a higher rate of responding for a
      conditioned stimulus and for food on a progressive ratio schedule of
      reinforcement, both of which were enhanced to a greater extent in isolates
      following administration of cocaine (5 mg/kg) and d-amphetamine (0.5 mg/kg).
      These results suggest that isolation rearing induces an enhancement in
      sensitivity to both the locomotor stimulant and reinforcing properties of
      amphetamine and cocaine.

PMID- 9181633
TI  - Enhancement by flumazenil of dopamine release in the nucleus accumbens of rats
      repeatedly exposed to diazepam or imidazenil.
AB  - The effect of long-term treatment (three times daily for 3 weeks) with a
      behaviorally relevant dose of the benzodiazepine receptor partial agonist
      imidazenil (0.5 mg/kg, IP) on basal dopamine release in the nucleus accumbens of
      freely moving rats was compared with that of diazepam (3 mg/kg, IP), a
      benzodiazepine receptor full agonist. Challenge doses of imidazenil and diazepam
      decreased the extracellular dopamine concentration in the nucleus accumbens by
      approximately the same extent in animals repeatedly exposed to vehicle or to the
      respective drug. Moreover, the abrupt discontinuation of long-term treatment with
      diazepam or imidazenil failed to affect basal dopamine release in this brain area
      during the first 5 days of withdrawal. In contrast, administration of the
      benzodiazepine receptor antagonist flumazenil (4 mg/kg, IP) elicited a marked
      increase (95 or 60%) in dopamine release in the nucleus accumbens 6 h after
      withdrawal of diazepam or imidazenil, respectively. Flumazenil induced a similar
      but smaller effect (50% increase) 5 days after diazepam withdrawal but had no
      effect 5 days after discontinuation of imidazenil treatment. The results support
      an involvement of the mesoaccumbens dopaminergic neurons in the withdrawal
      syndrome precipitated by flumazenil and allow further differentiation of
      benzodiazepine receptor partial and full agonists with respect to dependence
      liability of dopaminergic neurons in the nucleus accumbens.

PMID- 9181634
TI  - Pharmacological interactions between serotonin and dopamine on behavior in the
      squirrel monkey.
AB  - The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were
      determined in squirrel monkeys trained to respond under a fixed-interval (FI)
      schedule of stimulus termination and a second-order schedule of IV drug self
      administration. Intermediate doses of GBR 12909 increased FI response rate
      markedly, and the highest dose decreased response rate below control values. The
      5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist,
      quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the
      5HT2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the
      lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin
      increased response rate maintained by the highest dose. The dopamine agonist,
      quinpirole, increased FI response rate in only one of three subjects, and
      ritanserin enhanced the behavioral-stimulant effects of quinpirole in that
      subject. The dopamine agonist, apomorphine, only decreased FI response rate, and
      ritanserin did not alter its behavioral effects. The pharmacological profile of
      GBR 12909 administered alone and in combination with selective 5HT drugs in the
      present study was similar to that obtained previously with cocaine, further
      demonstrating that 5HT can reliably modulate the behavioral effects of
      psychomotor stimulants with prominent dopaminergic actions.

PMID- 9181635
TI  - Effects of stimulation of alpha 1-adrenergic and NMDA/glycine-B receptors on
      learning defects in aged rats.
AB  - The present study was designed to investigate the efficacy of stimulation of
      alpha1-adrenoceptors and the strychnine insensitive glycine-B binding sites of
      the N-methyl-D-aspartate (NMDA) receptor complex to alleviate the age-related
      defect in water maze (WM) spatial (hidden platform) navigation. We found that
      daily pretraining IP treatment with 2-(2-chloro-5-trifluoromethylphenylamino)
      imidazole nitrate (ST 587), an alpha1-adrenoceptor agonist, at 3000
      micrograms/kg, but not at 1000 micrograms/kg, facilitated acquisition of water
      maze spatial navigation in aged rats. However, ST 587 3000 micrograms/kg (IP) did
      not stimulate WM spatial reversal learning or cue navigation to a visible
      platform in aged rats. A partial strychnine insensitive glycine-B binding site
      agonist, D-cycloserine (DCS) at 10000 micrograms/kg stimulated acquisition of WM
      navigation, but had no effect on reversal learning or cue navigation. DCS at 1000
      or 3000 micrograms/kg (IP) had no marked effect on WM spatial navigation, and did
      not enhance the WM performance improving effect of ST 587 in aged rats. A
      subthreshold dose of ST 587 1000 micrograms/kg did not enhance the therapeutic
      effect of DCS 1000 micrograms/kg. The present results indicate that activation of
      alpha1-adrenoceptors and glycine binding sites of NMDA receptor may to some
      extent alleviate the age-related defect in spatial navigation. DCS treatment does
      not enhance the therapeutic effects of ST 587 and vice versa.

PMID- 9181636
TI  - 8-OH-DPAT, a 5-HT1A agonist and ritanserin, a 5-HT2A/C antagonist, reverse
      haloperidol-induced catalepsy in rats independently of striatal dopamine release.
AB  - In this study, both catalepsy and changes in extracellular levels of striatal
      dopamine (DA) and dihydroxyphenyl acetic acid (DOPAC) induced by the typical
      neuroleptic haloperidol (HAL) were simultaneously assessed, using intracerebral
      microdialysis in freely moving rats, in the presence of either the 5-HT1A agonist
      8-OH-DPAT or the 5-HT2A/C antagonist ritanserin. HAL (1 mg/kg, SC) elicited a
      strong cataleptic state, reaching its maximal intensity (about 240 s) 2 h after
      the drug administration. This effect was paralleled by a long-lasting enhancement
      of striatal DA and DOPAC extracellular levels, reaching 230 and 350% of basal
      values, respectively. 8-OH-DPAT (0.1 mg/kg, SC) given 2.5 h after, and ritanserin
      (0.63 and 1.25 mg/kg, IP), given 15 min prior to HAL, significantly reduced the
      neuroleptic-induced catalepsy. However, both 5-HT agents failed to modify basal
      DA and DOPAC striatal outflow as well as the stimulatory effect of HAL on these
      parameters. It can thus be concluded that the anticataleptic effect of these
      compounds is not related to an alteration of DA release within the striatum.

PMID- 9181637
TI  - Repeated administration of flumazenil does not alter its potency in modifying
      schedule-controlled behavior in chlordiazepoxide-treated rhesus monkeys.
AB  - Previous reports have suggested that the effects of the benzodiazepine antagonist
      flumazenil diminish over repeated exposure in subjects treated chronically with a
      benzodiazepine agonist. The current study examined whether the frequency of
      exposure to flumazenil altered its potency in decreasing rates of responding in
      monkeys treated with chlordiazepoxide (CDP). Three monkeys responded under a
      multiple fixed ratio (FR10:FR10) schedule of food presentation and stimulus-shock
      termination (SST). In untreated monkeys, flumazenil (0.1-3.2 mg/kg) had no effect
      in either component. After 2 weeks of treatment with 32.0 mg/kg per day of CDP,
      flumazenil decreased response rates in the food component, with a dose of 3.2
      mg/kg decreasing rates to 10% of control; rates in the SST component were not
      altered by flumazenil. When flumazenil dose-effect curves were redetermined at 28
      , 14-, 7-, 4-, 2- or 1-day intervals, there was no further change in the potency
      of flumazenil in decreasing food-maintained responding. When CDP treatment was
      terminated, the potency of flumazenil recovered to pre-CDP values within 23 days.
      These results suggest that dependence develops to CDP, since changes in the
      potency of flumazenil co-varied with CDP treatment. Moreover, it does not appear
      as though results from previous reports, that showed a diminished response to
      frequently-administered flumazenil, can be generalized to all conditions.

PMID- 9181638
TI  - Chiral drugs: comparison of the pharmacokinetics of [11C]d-threo and L-threo
      methylphenidate in the human and baboon brain.
AB  - Methylphenidate (Ritalin) is the most commonly prescribed psychoactive medication
      for children in the US where it is used for the treatment of attention deficit
      hyperactivity disorder. Methylphenidate is marketed as a racemic mixture of the d
      threo and l-threo enantiomers. It is believed that the d enantiomer is
      responsible for the therapeutic effect of methylphenidate. In this study we
      labeled the individual enantiomers with carbon-11 and compared their binding and
      pharmacokinetics in the human and baboon brain. Microdialysis studies in the rat
      were performed to compare their potency in elevating striatal dopamine
      concentration. Positron emission tomographic (PET) studies with [11C]d-threo
      methylphenidate ([11C]d-threo-MP) demonstrated highest regional uptake in basal
      ganglia. In contrast, [11C]l-threo-methylphenidate ([11C]l-threo-MP) displayed
      similar uptakes in all brain regions. The ratios of distribution volumes at the
      steady-state for the basal ganglia to cerebellum (DVBG/DVCB) ranged from 2.2 to
      3.3 for [11C]d-threo-MP in baboon and human, and only 1.1 for [11C]l-threo-MP.
      Pretreatment with unlabeled methylphenidate (0.5 mg/kg) or GBR12909 (1.5 mg/kg)
      markedly reduced the striatal but not the cerebellar uptake of [11C]d-threo-MP,
      whereas there was no effect on DVBG/DVCB for [11C]l-threo-MP. In the rat, d-threo
      MP increased extracellular dopamine concentration by 650% whereas l-threo-MP did
      not affect dopamine levels. These results indicate that pharmacological
      specificity of MP resides entirely in the d-threo isomer and directly show that
      binding of the l-isomer in human brain is mostly nonspecific.

PMID- 9181640
TI  - Reinstatement of drug-seeking behavior produced by heroin-predictive
      environmental stimuli.
AB  - The current study examined whether stimuli predictive of heroin availability were
      capable of inducing a relapse of drug-seeking behavior in an operant runway task.
      Olfactory stimuli (orange and almond food extract) served as discriminative cues
      about the availability (S+) or unavailability (S-) of heroin reinforcement (a
      single 0.1 mg/kg IV infusion) in the goal box of a straight arm runway. Following
      discrimination training, the running response was extinguished in the absence of
      the olfactory cues. On a single trial, the discriminative stimuli were then
      tested for their ability to reinstate running behavior prior to presentation of
      the heroin reinforcer. Subjects presented with the S+ on test day took
      significantly less time to traverse the alley than they did on the final day of
      extinction, while those subjects presented with the S- on test day continued to
      run slowly. These results demonstrate, in an animal model of drug self
      administration, that environmental discriminative cues can produce a relapse in
      drug seeking behavior following a period of abstinence. The response-reinstating
      properties of the S+ odor were unaltered by pretreatment with any of three doses
      of haloperidol (0.0, 0.15 or 0.3 mg/kg IP), suggesting that the motivating
      properties of heroin-predictive stimuli or cues remain intact during dopamine
      receptor antagonism.

PMID- 9181639
TI  - The attenuation of morphine-conditioned place preference following chronic mild
      stress is reversed by a CCKB receptor antagonist.
AB  - Chronic exposure to mild unpredictable stress has been found to abolish the
      acquisition of preference for a distinctive environment paired with morphine,
      whereas morphine induced conditioning place preference in non-stressed rats.
      Chronic treatment for 21 days with the tricyclic antidepressant imipramine
      reversed the motivational effects produced by chronic mild stress, and animals
      showed a place preference for the morphine-paired compartment. When the CCKB
      receptor antagonist PD-134,308 was co-administered with morphine in stressed
      animals during the conditioning period, the preference for the morphine-paired
      compartment was also re-established. The CCKB receptor antagonist given alone did
      not induce rewarding effects in this paradigm. These findings indicate that the
      administration of a CCKB receptor antagonist reversed the effects of chronic mild
      stress on opiate rewarding properties.

PMID- 9181641
TI  - Flesinoxan pretreatment differentially affects corticosterone, prolactin and
      behavioural responses to a flesinoxan challenge.
AB  - To determine whether alterations in 5-HT1A receptor mediated responses induced by
      a single injection with a selective 5-HT1A receptor agonist is a transient
      effect, or whether the (de)sensitisation is more persistent, rats were pretreated
      with the selective and full 5-HT1A receptor agonist, flesinoxan (3 mg/kg SC once
      daily) for either 1 day or 1 week. Twenty-four hour after the last pretreatment
      injection, rats were challenged with flesinoxan (3 mg/kg SC), and the effects on
      plasma corticosterone and prolactin levels, lower lip retraction and behaviour in
      the shock-probe burying test were determined. Several 5-HT1A receptor mediated
      responses were modified differentially following the flesinoxan pretreatment.
      However, all changes induced by a single flesinoxan injection remained present
      upon repeated flesinoxan administration. The differential changes in the
      responses to flesinoxan cannot easily be explained by differences in pre- or
      postsynaptically 5-HT1A mediated responses. The prolactin response to flesinoxan,
      which is thought to be mediated postsynaptically, was enhanced, whereas the
      corticosterone response to flesinoxan, which is also mediated postsynaptically,
      was attenuated. The presynaptically mediated lower lip retraction response was
      attenuated as well, whereas the behavioural effects of flesinoxan remained
      relatively unaffected following repeated flesinoxan administration. Upon
      prolonged flesinoxan pretreatment, the changes induced by a single flesinoxan
      injection remained present or increased further. Although repeated flesinoxan
      administration (1 day and 1 week) resulted in 20% lower plasma flesinoxan
      concentrations, this effect could not explain the neuroendocrine and behavioural
      findings.

PMID- 9181642
TI  - Hepatitis A immunity in the Swedish population. A study of the prevalence of
      markers in the Swedish population.
AB  - After a 20-year interval, the prevalence of seroimmunity to Hepatitis A (HA) was
      again investigated in a statistical sample of the adult Swedish population. Sera
      from 3382 of the 4800 originally selected persons were tested. The prevalence of
      antibodies to HA had not changed since the 1960s when only the Scandinavian
      population was considered. In the oldest population born at the beginning of this
      century, the presence of antibodies amounted to 69%. It gradually declined to 6%
      in those born in the 1940s. In the population born after 1950, the percentage of
      seropositive individuals was only 2%. A slightly higher prevalence was seen in
      the big cities, compared with the rural areas (13% vs 9%). Persons of non
      Scandinavian origin showed a different pattern. Those from other European
      countries showed a prevalence of about 70% in all the age-groups investigated.
      Among the young adults of Arabic or Asiatic origin, the figure was > 90%. The
      conclusion is that the native Swedish population has a low natural exposure to
      HA, which has not changed during the last 20 years. Prophylaxis before going to
      countries where the disease is endemic is strongly recommended.

PMID- 9181643
TI  - The impact of exposure group on the progression rate to acquired immunodeficiency
      syndrome. A comparison between intravenous drug users, homosexual men and
      heterosexually infected subjects.
AB  - The objective was to study the impact of exposure group on the progression rate
      to the acquired immunodeficiency syndrome (AIDS). 289 subjects in Oslo, Norway,
      infected with the human immunodeficiency syndrome (HIV) and without major
      clinical signs of HIV infection (102 intravenous drug users, 151 homosexual men
      and 36 heterosexually infected subjects) were recruited to the Oslo HIV Cohort
      Study from 1989 and followed until 1 January 1995. 15 (14.7%) of the intravenous
      drug users, 56 (37.1%) of the homosexual men and 5 (12.5%) of the heterosexually
      infected subjects developed AIDS during a mean time of 47 months (p < 0.001, log
      rank test). When controlling for possible confounding variables (age, number of
      CD4+ lymphocytes, antiviral therapy at study entry, gender and year of HIV
      diagnosis), the relative risk of AIDS progression was 2.2 [1.1-4.5, 95%
      confidence interval (CI)] for homosexual men and 0.5 (0.2-1.3, 95% CI) for
      heterosexually infected subjects as compared to intravenous drug users. In a
      subgroup with known time of seroconversion (n = 60), 47% (18/38) of the
      homosexual men, 20% (3/15) of the intravenous users and none (0/7) of the
      heterosexually infected subjects developed AIDS (p = 0.04, log rank test). The
      results suggest that homosexual men have more rapid progression to AIDS than
      intravenous drug users and heterosexually infected subjects.

PMID- 9181644
TI  - Coinfection and superinfection of hepatitis B virus in patients infected with
      human immunodeficiency virus: no evidence of faster progression to AIDS.
AB  - The influence of hepatitis B virus (HBV) on the natural history of human
      immunodeficiency virus (HIV) infection was evaluated in a prospective study of
      347 HIV-positive, AIDS-free individuals infected through injecting drug use and
      sex and with known seroconversion dates. End points were CD4+ cell count < 200 x
      10(6) cell/L and AIDS diagnosis. At entry, 229 had seromarkers to HBV; during the
      study, 107 had a CD4+ cell count < 200 x 10(6) cells/L and 66 developed AIDS.
      HBsAg chronic carriers, HBV infection-free subjects and those with baseline
      evidence of prior HBV infection did not differ in rates of progression to end
      points. Sexual transmission of HIV was significant predictor of CD4+ cell decline
      to < 200 x 10(6) cells/l [Hazard ratio (HZ): 1.56, 95% confidence interval (CI):
      1.06-2.29, p = 0.0232] and progression to AIDS (HZ: 1.91, CI: 1.17-3.11, p =
      0.0091). 15 HIV-positive and HBV infection-free patients had HBV seroconversion.
      They did not differ from those who remained HBV infection-free in rates of
      progression to end points, but 40% of them became HBsAg chronic carriers. These
      results suggest that HBV has no influence on progression of HIV disease, but that
      patients who have HIV before their HBV infection are more likely to become HBsAg
      chronic carriers than those who are infected with HBV before HIV.

PMID- 9181645
TI  - The serotonin analogue buspirone increases the function of PBMC from HIV-infected
      individuals in vitro.
AB  - HIV infection is characterized by the loss of CD4+ T cell numbers as well as loss
      of T cell function leading to severe immunodeficiency. The proliferative capacity
      of T cells, measured in vitro as response to antigens and mitogens, is severely
      reduced during HIV infection. An increased level of the intracellular second
      messenger cAMP has been demonstrated to cause impaired proliferative capacity of
      PBMC from HIV-infected individuals in vitro. We have identified a serotonin
      analogue, buspirone, that inhibits the activity of adenylyl cyclase, the enzyme
      responsible for regulation of intracellular levels of cAMP. Using this inhibitor
      the proliferative responses of PBMC to a polyclone activator in vitro were
      increased in 28/30 HIV-seropositive individuals (p < 0.00001). Further, we
      demonstrated that this was due to proliferation of CD4+ T cells and that
      buspirone induced expression of IL-2 mRNA.

PMID- 9181646
TI  - Alternating treatment with didanosine and zidovudine versus either drug alone for
      the treatment of advanced HIV infection. The Alter Study. Nordic HIV Therapy
      Group.
AB  - The efficacy and safety of an alternating regime with zidovudine and didanosine
      versus treatment with either drug alone were investigated in a randomized, open,
      controlled trial, 552 patients with advanced HIV infection, 47% of whom had
      received prior treatment with zidovudine, were enrolled. The patients were
      randomly assigned to zidovudine 600 mg/day, didanosine 400 mg/day or 4-week
      alternations with the 2 drugs in the same dose. The study had a median length of
      follow-up of 88 weeks. In the overall analyses, time to death (p = 0.48) and time
      to death or new AIDA event (0.80) were equally distributed between the 3
      treatment groups. In the subgroup of patients with a CD4 count < 100 x 10(6)/l
      the survival was longer in the alternating arm (p < 0.005) primarily because of
      differences among zidovudine naive patients. The alternating regime was better
      tolerated than the 2 monotherapies, with a longer time to dose reduction or
      withdrawal owing to side effects (p < 0.001).

PMID- 9181647
TI  - Primary and secondary infections by human parvovirus B19 following bone marrow
      transplantation: characterization by PCR and B-cell molecular immunology.
AB  - Due to the preparative regimen necessary, bone marrow transplantation (BMT)
      consistently results in severe immunodeficiency, often associated with anaemia,
      leukopenia and thrombocytopenia. Parvovirus B19 replicates in red blood cell
      precursors in the bone marrow and causes erythema infectiosum ('fifth disease'),
      anaemia, arthritis and foetal death. We assessed the significance of B19
      infections as a cause of post-BMT complications. Over 900 serial serum samples
      from 201 allogeneic bone marrow recipients were studied by polymerase chain
      reaction (PCR) and by modern serodiagnostic methods. During the first 6 months
      after transplantation all BMT recipients remained B19 PCR-negative. Antibody
      screening for B19 infections was performed up to 36 months post-transplantation.
      Three cases of acute B19 infection were diagnosed during the second year post
      BMT. To characterize the adoptively transferred immune system we measured
      subclasses and avidity of anti-VP1 IgG and epitope-type specificity (ETS) of anti
      VP2 IgG, which allowed functional differentiation of primary and secondary B-cell
      responses long after BMT. The profile of the immune response was that of a
      primary infection in 1 and of reinfection in 2 of the 3 acute cases. Both types
      were clinically mild. Infection by human parvovirus B19 is not a frequent cause
      of post-BMT cytopenias. The findings with the new B19 antibody markers support
      the concept that the donated marrow determines the type of antiviral B-cell
      responses.

PMID- 9181648
TI  - Measles antibodies and herd immunity in 20- and 40-year-old Norwegians.
AB  - The introduction of a measles vaccination programme in Norway in 1969 using one
      dose of vaccine, and since 1983 two doses, was followed by a substantial decrease
      in the incidence of the disease. Since 1992, the annual incidence has been less
      than 20 cases. Small clusters and outbreaks have occasionally been observed among
      military personnel and unvaccinated children. This paper describes a
      seroepidemiological investigation of the level of immunity among 1,188 military
      conscripts, aged 18-28 years (mean 20.7) compared with 695 healthy 40-year-olds.
      The conscripts had been offered measles vaccine in infancy, in some cases also at
      12-13 years of age, but they had also been exposed to wild measles virus, since
      the virus continued to circulate many years after the vaccination had started.
      The measles immunity in this group is considered to indicate the immunity level
      among the first 5 cohorts offered measles vaccine in Norway. The 40-year-olds had
      grown up in a community with no measles vaccination. Their level of immunity
      gives an indication of the level finally obtained when there are no vaccinations,
      and thus of the level that would induce herd immunity against measles in the
      Norwegian population. The aims of the vaccination programme must be to obtain a
      corresponding immunity. The results of the investigation show that the
      percentages with measles antibodies in the respective groups were 92.3 and 98.1.
      The observation of measles outbreaks among young Norwegian conscripts, as well as
      reports from several countries on outbreaks in university and college settings
      with levels of seropositivity of even more than 95%, indicate that the
      seropositivity in the 20-year-old group may be too low to afford protection,
      especially when this group is living under close conditions. Consideration should
      be given to the need for an intensification of the existing vaccination programme
      to ensure that the protection level needed for herd immunity is reached.

PMID- 9181650
TI  - The diagnostic value of enzyme immunoassay and immunoblot in monitoring
      eradication of Helicobacter pylori.
AB  - 55 patients with severe ulcer disease and H. pylori infection, successfully
      treated with antimicrobials, were followed-up with repeated blood samples for up
      to 32 months. Sera were analysed by enzyme immunoassay (EIA) for IgG and IgA
      antibodies and by IgG immunoblot. The EIA for IgG antibodies showed a high
      sensitivity (100%), while IgA antibodies above the cut-off level were found in
      55% of the patients. At a median of 77 days after onset of treatment,
      approximately 50% of the patients showed a significant decrease (> or = 50%) of
      IgG or had titres below the cut-off level. All patients but 1 had a significant
      decrease of IgG after 6-12 months. The decrease was slower for IgA. The H. pylori
      specific 116 kDa and 19.5 kDa bands were found in all pre-treatment samples, but
      the decrease in median intensity of the bands was slower than for the IgG EIA. In
      the 32-months post-treatment samples, both bonds had an intensity still above 50%
      of the pre-treatment value. The study showed that the IgG EIA is a useful method
      for monitoring eradication of H. pylori. Immunoblot can detect previous H. pylori
      infection in EIA negative Individuals.

PMID- 9181649
TI  - Loracarbef versus phenoxymethylpenicillin in the treatment of recurrent
      streptococcal pharyngotonsillitis.
AB  - Knowledge of the treatment of recurrent group A streptococcal pharyngotonsillitis
      has, so far, been based on studies of non-recurrent rather than recurrent
      episodes of the disease. This multicentre, double-blind, randomized trial was
      designed to compare the efficacy of loracarbef (200 mg twice daily) vs
      phenoxymethylpenicillin (penicillin V) (800/1000 mg twice daily) each for 10 days
      in the treatment of recurrent group A streptococcal pharyngotonsillitis. Among
      the 331 patients enrolled in the study, 265 were evaluable for efficacy. The
      combined clinical and bacteriological failure rate was 8.2% in the loracarbef
      group and 21.5% in the penicillin V group (p = 0.008). Bacterial eradication was
      noted in 90% of loracarbef-treated patients compared to 66% of penicillin V
      treated patients (p < 0.0005). The higher bacteriological eradication and
      clinical efficacy rate among loracarbef patients might be related to higher
      stability of loracarbef in the presence of beta-lactamases produced by the oral
      microflora. These results suggest loracarbef to be a strong candidate for
      treatment of patients with recurrent group A streptococcal pharyngotonsillitis.

PMID- 9181651
TI  - Lyme carditis: a clinical presentation and long time follow-up.
AB  - The acute disease and a follow-up carried out up to 7 years after definite Lyme
      carditis in 6 patients is described. At the time of diagnosis all 6 patients had
      2-3 degrees AV block, 4 patients presented with syncopes, and 1 revealed episodes
      of non-sustained ventricular tachycardia. The diagnosis of Lyme carditis was
      confirmed by Borrelia burgdorferi-specific IgM and IgG antibody determinations in
      consecutive serum samples. All patients were treated with antibiotics. At follow
      up, a clinical examination, a 2D and M-mode echocardiogram, and an exercise test
      did not reveal sequelae to Lyme carditis.

PMID- 9181652
TI  - Serum PCR of Pneumocystis carinii DNA in immunocompromised patients.
AB  - The detection of Pneumocystis carinii DNA in serum, a potentially useful and
      attractive tool for the diagnosis of P. carinii infection and for monitoring the
      success of therapeutic interventions, remains a controversial issue. In a
      prospective study of 29 immunocompromised patients, including 16 with HIV
      infection undergoing bronchoscopy and bronchoalveolar lavage, we examined 32
      bronchoalveolar lavage fluids and multiple serum samples for the presence of P.
      carinii DNA by using mitochondrial rRNA gene fragments pAZ102-E as pAZ102-H as
      primers. Samples from 7 immunocompetent patients were analysed as a control.
      13/32 bronchoalveolar lavage fluids of immunocompromised patients (41%), but none
      of the controls, had both microscopic evidence of P. carinii cysts as well as P.
      carinii DNA detection. In none of these patients were serum samples obtained
      before therapy positive for P. carinii DNA, while in 1 patient (8%), P. carinii
      DNA was detected in 2/5 serum samples obtained during therapy. Interestingly, PCR
      detected P. carinii DNA in sera of 3/15 immunocompromised patients without
      detection of P. carinii DNA or organisms in BAL. Two of these 3 patients were
      taking secondary prophylactics for P. carinii pneumonia. In conclusion, PCR for
      P. carinii DNA in serum, at least in certain circumstances, may be of little
      value for the diagnosis of P. carinii pneumonia.

PMID- 9181653
TI  - Albendazole treatment of human hydatid tissue.
AB  - The effect of albendazole was studied in 12 patients with cystic hydatid disease
      (CHD) of the liver. Six patients received albendazole continuously for 6 months,
      while 6 patients received albendazole for 6 courses of 4 weeks with a 2 week drug
      free interval between cycles. The continuous therapy proved successful, with
      stable involution at the follow-up at 24 months, while the patients treated with
      discontinuous therapy showed improvement or relapse. In our experience,
      continuous therapy was more effective and can be considered to be a suitable
      alternative or percutaneous therapy in uncomplicated hydatid liver disease, as an
      initial treatment.

PMID- 9181654
TI  - Patients with bacteremia dying before notification of positive blood cultures: a
      3-year clinical study.
AB  - In a 3-year prospective survey of bacteremia in a Danish county, 102 patients
      (4.6%) died before notification of positive blood cultures. Clinical records were
      available for 99 patients (ED group) with a male/female ratio of 1.15 and a
      median age of 74 years. The predominant pathogens were Escherichia coli (32%),
      Streptococcus pneumoniae (17%) and Staphylococcus aureus (16%). Streptococcus
      pneumoniae was the only pathogen found to be more frequently in the ED group than
      among patients who were alive when notification was issued (ALIVE group) (17% vs
      10%). All but 2 patients with meningococcal disease had a predisposing condition.
      Infection was deemed to be the direct cause of death in 62%, a contributory
      factor in 31% and of marginal significance in 6%. Compared with the ALIVE group,
      the ED group was older and more frequently had a focus within the respiratory
      tract. Conversely, the urogenital tract and intravascular devices were less
      common foci. The detection time was similar for the ED and ALIVE groups (median
      22 and 24 h, respectively). 78% of ED patients had received antibiotic therapy
      and the coverage was appropriate in 59%. The possibility of bacteremia had not
      been responded to by institution of antibiotic therapy in the remaining patients.
      We conclude that physicians must consider antibiotic therapy when ordering
      sampling of blood for culture and empirical antibiotic therapy should basically
      provide coverage for pneumococci, S. aureus and E. coli.

PMID- 9181655
TI  - Aminoglycosides do not improve the efficacy of cephalosporins for treatment of
      acute pyelonephritis in women.
AB  - A prospective, coordinated, randomized multicentre trial was conducted to
      determine whether tobramycin 160 mg intravenously (i.v.) once daily for 2 days
      would improve the efficacy of cefotaxime 1 g i.v. twice daily for 2 days followed
      by a 10-day course of oral cefadroxil 1 g twice daily, in the treatment of
      community-acquired acute pyelonephritis in women. Of 73 patients enrolled in the
      study, 51 could be evaluated according to the protocol. There were no significant
      differences in bacteriological cure rates between the combined treatment with
      tobramycin/cefotaxime and cefotaxime alone, either at short-term follow-up (63.0%
      vs 59.1%; 95% confidence interval (CI) for difference in proportions -23.4% to
      31.2%), or up to 7 weeks after cessation of treatment (42.9% vs 52.2%; 95% CI, 
      18.0% to 36.6%). A modified intention-to-treat analysis showed no difference in
      clinical efficacy between the two regimens (68.6% vs 69.2%; 95% CI, -22.9% to
      24.1%). Tobramycin seemed to enhance the resolution of inflammation by a more
      rapid decline in C-reactive protein levels. The high recurrence rates after
      treatment with beta-lactam antibiotics in this and previous studies of acute
      pyelonephritis may be explained by adverse ecological effects rather than failure
      to eradicate the infection.

PMID- 9181656
TI  - Influenza vaccination among healthy employees: a cost-benefit analysis.
AB  - The cost of influenza vaccination and influenza infections was evaluated in a
      controlled study among healthy municipal homemakers. Acute respiratory infections
      were followed clinically and with laboratory samples for 8 months. Full follow-up
      was achieved in 351 persons in the intervention group, of whom 47% obtained
      vaccination, and 492 controls. Influenza infection was confirmed in 10 employees
      (8 of these in the control group) and other viral infections in 6 employees (5 of
      them controls). All infections occurred in non-vaccinated persons. The relative
      risk of infection in the control group was 2.9 (95% CI 0.6-13.4) for influenza
      and 3.1 (0.9-10.8) for all respiratory infections. The mean sick leave for
      influenza was 4.9 days. The cost per immunization was FIM 141, and the average
      cost per influenza infection FIM 1183. The cost per infection averted was FIM
      6270, and the equivalent cost for immunization FIM 26.52. Influenza vaccination
      had a slight protective effect against both influenza and other respiratory
      infections. The cost of vaccination programmes exceeded the benefit from averted
      infections. Optimal vaccination strategies for healthy adults need to be planned
      individually with minimal loss of working time.

PMID- 9181657
TI  - Five cases of measles secondary vaccine failure with confirmed seroconversion
      after live measles vaccination.
AB  - We report 5 patients with secondary vaccine failure (SVF) who were infected with
      natural measles 2, 5, 5, 7 and 12 years, respectively, after vaccination with
      further attenuated live measles vaccine during infancy. Their seroconversion had
      been confirmed after vaccination. Three of the 5 patients had mild (modified)
      measles, while the remaining 2 patients had typical measles. The hemagglutination
      inhibition antibody titers to measles virus in paired acute and convalescent sera
      showed a secondary response pattern in 4/5 patients, and a primary response
      pattern was present in the remaining patient. Measles IgM antibodies were present
      in all patients during the convalescent stage. The patient with the primary
      response pattern may have had a decrease in the B cell memory during the 5-year
      period between vaccination and infection. This may be the first SVF case report
      that confirms the existence of completely waning immunity in recipients of the
      further attenuated live measles vaccines.

PMID- 9181658
TI  - Post-anginal sepsis (Lemierre's disease): a persistent challenge. Presentation of
      4 cases.
AB  - Four cases of lemierre's disease, or post-anginal (anaerobic) sepsis, are
      presented. All of the patients had polymicrobial infections. Two of the patients
      had serologically confirmed infectious mononucleosis. All patients required
      intubation and mechanical ventilation due to severe respiratory insufficiency.
      Two patients died after the development of severe septic shock with multiple
      organ dysfunction. The pathogenesis and clinical manifestations as well as the
      management of post-anginal sepsis are discussed.

PMID- 9181659
TI  - Isolation of dysgonic fermenter 3, a rare isolate associated with diarrhoea in
      immunocompromised patients.
AB  - CDC group DF-3 is a rare isolate from blood, stools and wounds. During the last
      few years attention to this bacterium has increased due to its association with
      diarrhoea and bacteremia in immunocompromised patients. This report presents an
      isolation of this bacterium from a decubitus ulcer of a subfebrile patient with
      diarrhoea.

PMID- 9181660
TI  - Campylobacter fetus subsp. fetus cholecystitis in a patient with advanced
      hepatocellular carcinoma.
AB  - Acute cholecystitis due to Campylobacter fetus subsp. fetus is very uncommon. We
      report a case of cholecystitis and obstructive jaundice in which cultured bile
      grew this organism. The patient had a 4-year history of hepatocellular carcinoma,
      resulting in common bile duct obstruction due to abdominal lymph node metastasis.
      Microscopic examination of her bile showed multiple Gram-negative curved
      organisms and C. fetus subsp. fetus was isolated under microaerophilic
      conditions. Therefore, we should be aware of this organism and use
      microaerophilic culture in association with the result of microscopic examination
      of bile specimens.

PMID- 9181661
TI  - Two patients with recurrent melioidosis after prolonged antibiotic therapy.
AB  - Melioidosis is a tropical infectious disease caused by Burkholderia (Pseudomonas)
      pseudomallei. Clinically manifest melioidosis occurs mostly in people with
      underlying disorders. Melioidosis is a disease with protein manifestations and a
      high rate of relapse. Two patients with infection due to Burkholderia
      pseudomallei after a visit to Thailand are described. Both patients presented
      with sepsis and appropriate therapy was initiated and continued for several
      months. Despite such long-term antimicrobial treatment, both patients had a
      relapse after cessation of therapy. It is unclear if recurrent melioidosis can be
      prevented by prolonging the treatment even further.

PMID- 9181662
TI  - Detection of Mycobacterium avium complex in cerebrospinal fluid of a sarcoid
      patient by specific polymerase chain reaction assays.
AB  - The etiology of sarcoidosis is unknown, but it has long been suspected to be
      mycobacterial. In the present study, we used 4 mycobacterial species-specific
      polymerase chain reaction assays on cerebrospinal fluid obtained from a patient
      with neurosarcoidosis. Positive hybridization was observed with both the
      Mycobacterium avium complex probe and the insertion element IS900-specific probe
      that has been found in M. paratuberculosis species. There was no hybridization
      with M. tuberculosis or M. avium woodpigeon strain-specific probes. This case
      report demonstrates that M. paratuberculosis or some closely related M. avium spp
      which perhaps also carry IS900, or contain closely related DNA sequences, are
      associated with at least some cases of sarcoidosis disease.

PMID- 9181663
TI  - CD4 lymphopenia in a patient with cryptococcal osteomyelitis.
AB  - Cryptococcus neoformans is a rarely reported cause of osteomyelitis. In most
      cases, no obvious underlying condition is found. Immunological laboratory data,
      however, are not generally available. In the present case of cryptococcal
      osteomyelitis, idiopathic CD4 lymphopenia was detected. This immunodeficiency is
      found in cases of disseminated cryptococcosis by chance. Possibly, it may be one
      so far unrecognized underlying condition in cryptococcal osteomyelitis.

PMID- 9181664
TI  - Halofantrine-associated ventricular fibrillation in a young woman with no
      predisposing QTc prolongation.

PMID- 9181665
TI  - Is exercise beneficial in the prevention of prostate cancer?
AB  - Prostate cancer is the most frequently diagnosed cancer in men. Exercise has been
      studied as an alterable risk factor that may reduce the incidence, morbidity and
      mortality due to this cancer. Epidemiological studies play an important role in
      assessing the relationship between physical activity and prostate cancer. Studies
      have attempted to estimate physical activity level by measuring time spent in
      sports, leisure or occupational activity. We identified 17 studies that assessed
      the effect of exercise on the development of prostate cancer. Although
      methodological limitations could be identified in most of the studies, 9
      suggested that exercise may be beneficial in decreasing prostate cancer risk,
      while 5 were null providing no conclusive evidence and 3 actually showed an
      increased risk of prostate cancer with increased physical activity. The bulk of
      the evidence at this time does not seem to support an overwhelmingly beneficial
      effect of exercise on prostate cancer risk. Future studies need to investigate
      the frequency, intensity and duration of physical activity as well as the type of
      activity and period during a man's lifetime when exercise might be beneficial. It
      is reasonable to conclude that exercise may be a potential factor that can be
      modified to prevent prostate cancer and it seems prudent to recommend that all
      men become physically active.

PMID- 9181666
TI  - Dietary sodium and plasma volume levels with exercise.
AB  - Sodium is the major cation of the extracellular fluid and has a potent influence
      on fluid movement. Sodium has been likened to a sponge that draws fluids into the
      extracellular space, including the plasma volume, to equalize gradients in
      concentration. Conventional wisdom suggests limiting dietary intake of Na+ to
      decrease risk of hypertension. However, there are some extreme occupational or
      exercise-related conditions where sweat losses are great and Na+ losses may
      exceed normal dietary intake. This can occur acutely such as in an ultra
      endurance event or chronically as in hard manual work in the hear. In such cases,
      additional Na+ in the form of a higher Na+ diet or adding Na+ to beverages used
      for fluid replacement may be warranted. A higher Na+ diet also appears to
      accelerate the cardiovascular and thermoregulatory adaptations that accompany
      heat acclimation or short term exercise training. Saline ingestion before
      exercise causes an expansion of plasma volume at rest and throughout the
      subsequent exercise bout. This expansion of plasma volume alters cardiovascular
      and thermoregulatory responses to exercise in ways that may lead to beneficial
      changes in endurance exercise performance. Plasma volume expansion also occurs
      with saline infusion during exercise, but exercise performance advantages have
      yet to be reported. The purpose of this article is to review the literature
      concerning dietary sodium and its influence on fluid balance, plasma volume and
      thermoregulation during exercise. It contains 2 major sections. First, we will
      discuss manipulations in daily Na+ intake initiated before or throughout an
      exercise regime. Second, we will examine studies where an acute Na+ load was
      administered immediately before or during an exercise trial. The dependent
      variables that we will discuss pertain to: (i) body water compartments, i.e.
      plasma volume; (ii) thermoregulatory variables, i.e. core temperature and sweat
      rate; (iii) cardiovascular variables, i.e. heart rate and stroke volume; and (iv)
      performance, i.e. time trial performance and time to exhaustion. Particular
      attention will be given to the route by which Na+ was administered, the
      environmental conditions, the level of acclimation of the participants and
      specifics relating to Na+ administration such as the osmolality of the Na(+)
      containing beverage.

PMID- 9181669
TI  - Psychological rehabilitation from sports injuries.
AB  - Medical professionals realise the importance of incorporating psychological
      strategies into rehabilitation from athletic injury, but often feel they lack the
      knowledge to do so. This paper explores the role which psychology can play when
      injured athletes are rehabilitating. Rehabilitation from sport injury involves
      not only physical, but psychological considerations. Topics include: the post
      injury emotional and cognitive reactions of athletes, the importance of social
      support, the athlete's attitude toward recovery, the therapist's, physician's and
      coach's roles during rehabilitation, strategies to increase adherence, and
      effective communication between client and medical professionals. Considerations
      for returning to practice and competition are also discussed.

PMID- 9181667
TI  - Muscle contraction and fatigue. The role of adenosine 5'-diphosphate and
      inorganic phosphate.
AB  - Though many explanations are offered for the fatigue process in contracting
      skeletal muscle (both central and peripheral factors), none completely explain
      the decline in force production capability because fatigue is specific to the
      activity being performed. However, one needs to look no further than the muscle
      contraction crossbridge cycle itself in order to explain a major contributor to
      the fatigue process in exercise of any duration. The byproducts of adenosine 5'
      triphosphate (ATP) hydrolysis, adenosine 5'-diphosphate (ADP) and inorganic
      phosphate (Pi) are released during the crossbridge cycle and can be implicated in
      the fatigue process due to the requirement of their release for proper
      crossbridge activity. Pi release is coupled to the powerstroke of the crossbridge
      cycle. The accumulation of Pi during exercise would lead to a reversal of its
      release step, therefore causing a decrement in force production capability. Due
      to the release of Pi with both the immediate (phosphagen) energy system and the
      hydrolysis of ATP, Pi accumulation is probably the largest contributor to the
      fatigue process in exercise of any duration. ADP release occurs near the end of
      the crossbridge cycle and therefore controls the velocity of crossbridge
      detachment. Therefore, ADP accumulation, which occurs during exercise of extended
      duration (or in ischaemic conditions), causes a slowing of the rate constants
      (and therefore a decrease in the maximal velocity of shortening). in the
      crossbridge cycle and a reduced oscillatory power output. The combined effects of
      these accumulated hydrolysis byproducts accounts for a large amount of the
      fatigue process in exercise of any intensity or duration.

PMID- 9181670
TI  - Teratogenic effects of vigabatrin in TO mouse fetuses.
AB  - Vigabatrin (VGB) is a relatively recently introduced antiepileptic drug that
      enhances the brain levels of gamma aminobutyric acid (GABA). Few data on its
      teratogenic effects appear to have been reported. Our objective was to determine
      if VGB was teratogenic in the TO mouse. Single doses of 300-600 mg/kg of VGB
      dissolved in saline were administered intraperitoneally (IP) to groups of TO mice
      on one of gestation days (GD) 7-12. The controls were saline treated or
      untreated. No maternal toxic effects were observed in the 300 or 450 mg/kg
      groups, and the 600 mg/kg dose was totally lethal to the mothers. Fetuses were
      collected on GD 18. Both 300 and 450 mg/kg doses induced a consistently
      significant intrauterine growth retardation irrespective of the developmental
      stage at administration. VGB did not augment the spontaneous incidence of neural
      tube defects characteristic of this strain, but accelerated destruction of the
      brain in spontaneous exencephalic embryos. Mandibular and maxillary hypoplasia,
      arched palate, cleft palate (two cases), limb defects (one case), and exomphalos
      were observed in the malformed fetuses. The high incidence of exomphalos appears
      to be a unique result of VGB treatment. Alizarin red-S/alcian blue-stained,
      skeletons revealed hypoplasia of mid facial bones, stage-dependent increase in
      the frequency of cervical and lumbar ribs, rib fusion, and sternal and vertebral
      malformations in the drug-treated fetuses. Middle and distal phalanges of the
      forepaw and mid phalanges and tarsals of the hindpaw failed to ossify in a
      significant number of experimental fetuses. Homeotic shift in terms of presacral
      vertebral number and a high incidence of lumbar and cervical ribs in the treated
      group are suggestive of treatment-related alterations in gene expression. In view
      of the paucity of human and animal data on the reproductive toxicologic effects
      of VGB, the results of the present study assume particular importance and suggest
      that VGB should be used in pregnancy with extreme caution.

PMID- 9181671
TI  - Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine
      prenatally: implications for perinatal morbidity and mortality, and for sudden
      infant death syndrome.
AB  - Maternal smoking correlates highly with parturitional/neonatal death including
      SIDS; nicotine exposure of fetal rats reproduces the increased mortality when
      animals are tested postnatally with hypoxia. In the current study, pregnant rats
      received nicotine infusions simulating smokers' plasma nicotine levels. At 1-2
      days postpartum, the nicotine group displayed normal heart rates, EKG waveforms,
      and respiratory rates in normoxia. With hypoxia (5% O2, 10 min), controls showed
      initial tachycardia and a subsequent slight decline in heart rate;
      atrioventricular conduction was gradually impaired and repolarization
      abnormalities also appeared. The nicotine group showed no tachycardia and heart
      rate declined rapidly and precipitously within a few minutes after commencing
      hypoxia; otherwise, EKG alterations mimicked the controls'. Changes in
      respiration were identical in the two groups: initial tachypnea and subsequent
      decline. These results suggest that prenatal nicotine affects sinoatrial
      reactivity to hypoxia without impairing cardiac conduction per se. These
      mechanisms explain increased hypoxia-induced mortality in animals exposed to
      prenatal nicotine, and in man could account for increased morbidity/mortality and
      SIDS. Our results also indicate the need to test adverse effects of fetal drug
      exposure using conditions that challenge any given physiological system rather
      than relying solely on changes under basal conditions.

PMID- 9181672
TI  - Spontaneous and induced alterations in the cardiac membranous ventricular septum
      of fetal, weanling, and adult rats.
AB  - Alterations of the cardiac membranous ventricular septum were studied using
      macrodissection, scanning electron and light microscopy of fetal, weanling, and
      adult Sprague-Dawley rats. Membranous ventricular septal defects (VSDs) were
      observed in 2.0% of fetuses on day 21 postcoitus (pc) but not in weanling or
      adult rats. The most common observation was a nonpatent depression in the
      membranous septum with an incidence of 38.1, 10.5, 4.3% for fetuses on days 17,
      19, or 21 pc, respectively, 11.8% for weanlings, and 9.1% for adults. VSDs were
      characterized by a split in the endocardial cushion cells in the interventricular
      component of the membranous septum. Nonpatent depressions were characterized by a
      split in the endocardial cushion cells in the atrioventricular component of the
      septum, and they persisted postnatally as a blind-ended diverticulum directed
      above the tricuspid valve. The cardiovascular teratogens, trimethadione and
      trypan blue, produced in fetuses nonpatent depressions and VSDs morphologically
      similar to untreated fetuses. Maternal diet restriction (25% of controls) lowered
      fetal (day 21 pc) body weight by 47% but did not affect the incidence of
      ventricular septal alterations, suggesting that intrauterine growth retardation
      is not necessarily associated with alterations in the development of the
      ventricular septum. We conclude that neither VSDs nor nonpatent depressions in
      Sprague-Dawley rats affect postnatal survival and that VSDs close spontaneously
      during neonatal life.

PMID- 9181668
TI  - Walking to health.
AB  - Walking is a rhythmic, dynamic, aerobic activity of large skeletal muscles that
      confers the multifarious benefits of this with minimal adverse effects. Walking,
      faster than customary, and regularly in sufficient quantity into the 'training
      zone' of over 70% of maximal heart rate, develops and sustains physical fitness:
      the cardiovascular capacity and endurance (stamina) for bodily work and movement
      in everyday life that also provides reserves for meeting exceptional demands.
      Muscles of the legs, limb girdle and lower trunk are strengthened and the
      flexibility of their cardinal joints preserved; posture and carriage may improve.
      Any amount of walking, and at any pace, expends energy. Hence the potential, long
      term, of walking for weight control. Dynamic aerobic exercise, as in walking,
      enhances a multitude of bodily processes that are inherent in skeletal muscle
      activity, including the metabolism of high density lipoproteins and
      insulin/glucose dynamics. Walking is also the most common weight-bearing
      activity, and there are indications at all ages of an increase in related bone
      strength. The pleasurable and therapeutic, psychological and social dimensions of
      walking, whilst evident, have been surprisingly little studied. Nor has an
      economic assessment of the benefits and costs of walking been attempted. Walking
      is beneficial through engendering improved fitness and/or greater physiological
      activity and energy turnover. Two main modes of such action are distinguished as:
      (i) acute, short term effects of the exercise; and (ii) chronic, cumulative
      adaptations depending on habitual activity over weeks and months. Walking is
      often included in studies of exercise in relation to disease but it has seldom
      been specifically tested. There is, nevertheless, growing evidence of gains in
      the prevention of heart attack and reduction of total death rates, in the
      treatment of hypertension, intermittent claudication and musculoskeletal
      disorders, and in rehabilitation after heart attack and in chronic respiratory
      disease. Walking is the most natural activity and the only sustained dynamic
      aerobic exercise that is common to everyone except for the seriously disabled or
      very frail. No special skills or equipment are required. Walking is convenient
      and may be accommodated in occupational and domestic routines. It is self
      regulated in intensity, duration and frequency, and, having a low ground impact,
      is inherently safe. Unlike so much physical activity, there is little, if any,
      decline in middle age. It is a year-round, readily repeatable, self-reinforcing,
      habit-forming activity and the main option for increasing physical activity in
      sedentary populations. Present levels of walking are often low. Familiar social
      inequalities may be evident. There are indications of a serious decline of
      walking in children, though further surveys of their activity, fitness and health
      are required. The downside relates to the incidence of fatal and non-fatal road
      casualties, especially among children and old people, and the deteriorating air
      quality due to traffic fumes which mounting evidence implicates in the several
      stages of respiratory disease. Walking is ideal as a gentle start-up for the
      sedentary, including the inactive, immobile elderly, bringing a bonus of
      independence and social well-being. As general policy, a gradual progression is
      indicated from slow, to regular pace and on to 30 minutes or more of brisk (i.e.
      6.4 km/h) walking on most days. These levels should achieve the major gains of
      activity and health-related fitness without adverse effects. Alternatively, such
      targets as this can be suggested for personal motivation, clinical practice, and
      public health. The average middle-aged person should be able to walk 1.6 km
      comfortably on the level at 6.4 km/h and on a slope of 1 in 20 at 4.8 km/h,
      however, many cannot do so because of inactivity-induced unfitness. The
      physiological threshold of 'comfort' represents 70% of maximum heart rate.
      (ABSTRACT TRUNCATED)

PMID- 9181673
TI  - Changes in cell adhesion and extracellular matrix molecules in spontaneous spinal
      neural tube defects in avian embryos.
AB  - Quail embryos (embryonic days 2-2.5) with spontaneous neural tube defects (NTDs),
      along with age-matched normal embryos, were examined immunocytochemically for the
      extracellular matrix (ECM) molecules laminin, fibronectin, and chondroitin
      sulfate proteoglycan, the cell adhesion molecules (CAMs) E- and N-cadherin and
      neural CAM (NCAM), and the neural crest marker HNK-1. The embryos with NTDs were
      at the lower limit of the normal stage range and the affected region was about
      25% shorter than in normal embryos. Open NTDs occurred in cervical and upper
      thoracic level, although often the ventral neural tube was morphologically
      normal. Widened, irregular but closed neural tubes (lower thoracic to sacral
      levels) showed disorganized mesenchyme-like cells centrally and often multiple
      lumens. Finger-like tabs projecting from the ectoderm over the neural tube also
      occurred at lower thoracic to sacral levels. In open NTDs, the E-cadherin-labeled
      epidermis was incomplete dorsally, and was continuous with the N-cadherin-labeled
      neural tissue, with a sharp demarcation between E- and N-cadherin-expressing
      regions, as in the early stages of normal primary neurulation. A sharp inverted
      peak of epidermis extended ventrally, closely applied to the side of the neural
      tissue. The intervening matrix labeled less intensely for chondroitin sulfate
      proteoglycan relative to laminin and fibronectin, in comparison to control
      embryos. In closed NTDs, the dorsal superficial cell layer (i.e., positionally
      epidermis) was not separated from the underlying neural tissue by a band of
      matrix as in control embryos. In addition, this layer expressed E-cadherin (as in
      normal embryos), but coexpressed N-cadherin and NCAM, which are not normally
      found here at this stage. This overlap region resembled the mid-dorsal tissue at
      earlier stages in normal secondary neurulation in the tail-bud. The tabs of
      tissue appeared to be localized hypertrophy of the epidermal and neural ectoderm,
      and also showed codistribution of E- and N-cadherin. In all these defects, matrix
      molecules occurred within (rather than around) the neural and epidermal
      epithelia. HNK-1-labeled neural crest cells were frequently absent in regions of
      NTDs, in contrast to control embryos. These results show that matrix and cell
      adhesion molecules are disturbed in spontaneous NTDs at the time of neurulation,
      and therefore could be involved in the generation of the defects by altering cell
      adhesion-dependent morphogenetic events.

PMID- 9181675
TI  - Synthesis of a series of Homopterocarpane derivatives with potential antitumor
      and anti-AIDS activity.
AB  - The synthesis of a series of derivatives related to (+/-) cis 6a, 12a-dihydro
      6H,7H-[1]-benzopyrano-[4,3-b]-[1]-benzopyran (Homopterocarpane) is described. The
      synthesized derivatives have been tested at National Cancer Institute in its in
      vitro anti-cancer and anti-AIDS screening programs. The synthesized compounds are
      inactive in anti-HIV assay, while some show a GI50 < 100 microM (and < 50 microM
      in several cell lines) in NCI antitumor screening.

PMID- 9181674
TI  - Synthesis and biological properties of some 2H-1-benzopyrano[7,8
      b][1,4]benzodioxin-2-ones.
AB  - The synthesis of 2H-benzopyrano[7,8-b][1,4]tetrahydrobenzodioxin-2-ones and 2H
      benzopyrano [7,8-b][1,4]benzodioxin-2-ones is reported. This class of compounds,
      prepared with the aim of obtaining new monofunctional photosensitizing drug,
      appears to be ineffective upon UVA irradiation but shows a moderate but
      significant activity in the dark.

PMID- 9181676
TI  - Synthesis and antimicrobial activity of N-(1,2-benzisothiazol-3-yl)amidines.
AB  - Several N-(1,2-benzisothiazol-3-yl)amidines were synthesized and examined for
      their in vitro antimicrobial activity. Some of the compounds studied were
      effective against bacteria and fungi. Amidines carrying unsaturated alkylic
      chains showed the highest antimicrobial activity, the propenyl derivative 7
      proving to be the most potent with minimum inhibitory concentrations of 25
      micrograms/ml against Gram positive bacteria and mould and of 3-12 micrograms/ml
      against yeasts. The results indicate that an unsaturated moiety is an important
      function for enhancing the antimicrobial activity in the compounds under
      investigation.

PMID- 9181677
TI  - Synthesis and pharmacological evaluation of 4,4a,5,6-tetrahydro-7,8-disubstituted
      benzo[h]cinnolin-3(2H)-ones.
AB  - 7,8-disubstituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones 2-4 have been
      synthesized and tested in comparison with the 8-acetylamino-4,4a,5, 6
      tetrahydrobenzo[h]cinnolin-3(2H)-one 1 reported to be a potent antihypertensive
      and antithrombotic agent. Binding studies on phosphodiesterase (PDE) isoenzymes
      showed that the test compounds exhibited a modest affinity towards PDE III which
      in the case of 2, 3 was higher than that of 1. In vivo tests indicated that
      compounds 2 and 4 displayed lower hypotensive activity than model 1 while 3 was
      inactive. Conversely, compounds 2-4 were as potent as 1 in inhibiting collagen
      induced platelet aggregation.

PMID- 9181678
TI  - Synthesis and pharmacological evaluation of 4a-methyl-4,4a,5,6
      tetrahydrothieno[2,3-h]cinnolin-3(2H)-ones.
AB  - A number of 4a-methyl-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolin-3(2H)-one s (3-5)
      have been synthesized and tested for their pharmacological profile. These were
      compared with the 8-acetylamino-4, 4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)one 1
      which we reported to be a potent antihypertensive agent. In vivo tests indicated
      that 3 displayed lower even if still significant levels of antihypertensive
      activity in respect to the lead compound, while all the new derivatives exhibited
      lower hypotensive activity. Tricyclic thienocinnolinones 3-5 demonstrated fairly
      potent plateled antiaggregatory activity.

PMID- 9181679
TI  - Tripeptide methylketones: synthesis and antiplasmin activity.
AB  - A series of tripeptide methylketones with C-terminal lysine was obtained via
      Dakin-West method and tested for their antiplasmin activity with the use of
      antifibrinolytic and antiamidolytic tests. The tripeptide methylketones has been
      found to inhibit plasmin, however with much lower potency than respective
      aldehydes.

PMID- 9181680
TI  - Synthesis and biological activities of higher homologues of retinoic acid.
AB  - Homoretinoic and bishomoretinoic acid have been synthesized. Fast reaction under
      ultrasonic activation (Wolff rearrangement, saponification) produced compounds in
      high yields. Only the bishomo analogue exhibits a significative activity alone
      and a synergistic effect with vitamin D3 on the differentiation of U937 leukemic
      cell line.

PMID- 9181681
TI  - 3,3'-Bi(1,3-thiazolidin-4-one) system. VIII. 3,3'-(1,2-Ethanediyl) derivatives
      and corresponding 1,1'-disulfones: synthesis, stereochemistry and
      antiinflammatory activity.
AB  - To deeply investigate the influence of lipophilicity, phenyl substitution
      patterns and stereo-chemistry on pharmacological profiles of chiral
      bisarylthiazolidinones, frequently endowed with stereoselective antiinflammatory,
      analgesic, antihistaminic activities, we synthesized and explored some 3,3'-(1,2
      ethanediyl) analogues 1-4, along with their S-oxidized derivatives 5-8. Each
      derivative can be isolated as 2R, 2'R/2S, 2'S (a) and 2R, 2'S- or 2S, 2'R- meso
      (b) diastereomers, which were explored by means of carrageenin edema test, acetic
      acid writhing and hot plate tests, and also tested for gastrolesive potential and
      LD50. Independently of lipophilic and electronic features, disulfides 3b, 4b and
      disulfones 7a, 8a, 8b displayed interesting activity levels which appear to be
      mainly linked to the disubstitution pattern on benzenic rings.

PMID- 9181682
TI  - 1,8-Naphthyridines. III. N,N-dialkyl-5-chloro[1,2,4]-triazolo[4,3
      a][1,8]naphthyridine-6-carboxa mides with anti-inflammatory activity.
AB  - Fifteen N,N-dialkyl-5-chloro[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxami
      des (7a-o) were synthesized through the cyclocondensation of the corresponding
      N,N-dialkyl-2,4-dichloro-1,8-naphthyridine-3-carboxamides with proper hydrazides,
      in order to evaluate their anti-inflammatory, antiaggressive, and analgesic
      properties. Four of the compounds tested showed a statistically significant and
      dose-dependent anti-inflammatory activity.

PMID- 9181683
TI  - Synthesis of cis- and trans- 2-arylmethylcycloalkylamines: potential dopaminergic
      agents.
AB  - This paper reports the synthesis and the study of a few new diastereomeric
      arylmethylcycloalkylamines, tested as potential dopamine receptor active agents.
      New procedures for the stereospecific synthesis of the arylmethylcycloalkylamines
      were successfully experimented. All the considered compounds did not show any
      appreciable dopamine receptor activity.

PMID- 9181684
TI  - Synthesis of 4,6-disubstituted- and 4,5,6-trisubstituted-2-phenyl-pyrimidines and
      their affinity towards A1 adenosine receptors.
AB  - Synthesis and assay of title compounds are reported. The results can support our
      hypothesis about the possibility that molecules characterized by great
      flexibility, as the title 2-phenyl-4,5,6-triaminopyrimidines, can better interact
      with the receptor sites compared with rigid molecules as 2,6,9-trisubstituted 8
      azaadenines. Relatively low activity shown by pyrimidine derivatives demonstrated
      the importance of the bicyclic aromatic system in 8-azaadenines and adenines to
      give a favourable interaction between a hexogenous molecule and the A1 adenosine
      receptors.

PMID- 9181686
TI  - In vitro and in vivo antitumor activity of immunoconjugates prepared by linking 5
      fluorouridine to antiadenocarcinoma monoclonal antibody.
AB  - 5-Fluorouridine (5-FUr), a cytotoxic antitumoral agent not in clinical use
      because of its systemic toxicity, and AR-3, a monoclonal antibody specific to a
      human colorectal adenocarcinoma, were covalently linked via two different
      strategies. 5-FUr was 5' succinilated after protection of the secondary hydroxyl
      groups and the carboxylate derivative was then activated as N-hydroxysuccinimidyl
      ester in order to react with the amino groups present in the monoclonal antibody,
      giving an amide linkage. Alternatively, a 5-FUr immunoconjugate containing an
      acid-cleavable hydrazone bond was formed from the reaction between an acyl
      hydrazide derivative of 5-FUr and a periodate oxydized antibody with
      approximately 12 aldehyde groups in its carbohydrate region. An average of 9 to
      12 drug molecules were attached to the antibody. In a cytotoxic assay on the
      human colorectal carcinoma cell line HT-29, the hydrazone containing drug
      conjugate was equally active as the succinylamido conjugate and the free drug.
      However, ELISA showed that while in the case of the succinylamido conjugate the
      Mab immunoreactivity was not affected after conjugation, there was a significant
      loss of reactivity in the acid cleavable conjugate. In a model of a disseminated
      intraabdominal carcinomatosis by HT-29 intraperitoneal graft in nude mice, the 5
      FUr immunoconjugate selected was more effective than the unconjugated drug in
      medium-term therapy (21 days after the graft and 16 days after drug treatment),
      albeit in the longer period the efficacy of the two formulations was similar. The
      toxic effect of the drug-conjugate in vivo was much weaker, demonstrating its
      clear advantage over the drug, in terms of pharmacological efficacy.

PMID- 9181685
TI  - Pyridazine N-oxides. II. Synthesis and in vitro antimicrobial evaluation of 3
      chloro-4-carbamoyl-5-aryl-6-methyl-pyridazine N-oxides.
AB  - As a part of a research project on antimicrobial agents, various novel carbamoyl
      derivatives of pyridazine-N-oxides 7a-j were prepared in moderate to good yields
      from 3-chloro-4-ethoxycarbonyl-5-aryl-6-methyl-3-pyridazine. All compounds
      synthesized were ineffective against Gram+, Gram- bacteria and fungi while 7e and
      7j exhibited a fairly good activity against Trichomonas vaginalis.

PMID- 9181687
TI  - Studies on o-[2,6-dichlorophenyl-1-amino] phenyl acetic acid. I. Synthesis,
      antiinflammatory, analgesic and ulcerogenic activities of some new amino acid
      conjugates.
AB  - o-[2,6-Dichlorophenyl-1-amino]phenyl acetic acid (diclofenac) (I) reacted with
      some amino acid esters, namely glycine, L-valine, L-diiodotyrosine and L
      tryptophan through the active ester to give the corresponding o-[2,6
      dichlorophenyl-1-amino]benzyl carboxy-N-amino acid ester of the type (IIa-d),
      respectively, which were hydrolysed in alkaline medium to yield the free amino
      acids (IIIa-d). Condensation of the latter compounds with hydrazine hydrate gave
      the corresponding acid hydrazides (IVa-d), which in turn were reacted with
      trimethoxybenzaldehyde to give the corresponding Schiff's bases (Va-d),
      respectively. The antiinflammatory, ulcerogenic and analgesic activities of the
      obtained compounds were also investigated.

PMID- 9181688
TI  - Synthesis of thiophene carboxamide derivatives as serotonin 5-HT4 receptor
      agonists.
AB  - New thiophene carboxamide derivatives 3 (a-j) were synthesized as serotonin 5-HT4
      receptor agonists. Preliminary results showed that the compounds 3a, 3d, 3e and
      3f caused concentration dependent relaxation of carbachol-induced contraction in
      tunica muscularis mucosae in rat oesophagus.

PMID- 9181689
TI  - Synthesis of amides with anti-inflammatory and analgesic activities.
AB  - A series of N-Aroyl-cyclohexyl- and cyclohexenylamides 3- or 4-methylsubstituted
      were synthesized and evaluated for their anti-inflammatory and analgesic
      potencies, and gastrointestinal irritation liability. One compound, N-benzoyl-4
      methyl-cyclohexylamide 6a, possessed an anti-inflammatory activity comparable to
      that of indomethacin.

PMID- 9181690
TI  - Synthesis and structure-activity relationships of some 2,5-disubstituted
      benzoxazoles and benzimidazoles as antimicrobial agents.
AB  - The synthesis of a new series of 2,5-disubstitutedbenzoxazoles 5a-e, and 2,5
      disubstitutedbenzimidazoles 6a-h are described in order to determine their
      antimicrobial activities and feasible structure-activity relationships (SAR). The
      synthesized compounds were tested in vitro against 3 Gram-positive, 3 Gram
      negative, bacteria and a fungus Candida albicans. 5c, and 5e were found most
      active than the others against Bacillus subtilis at a MIC value of 3.12
      micrograms/ml and the compounds 5e, 6a and 6e indicated significant antibacterial
      activity against the enterobacter Pseudomonas aeruginosae. 5a, 5c, 5d and 6d also
      exhibited antimycotic activity against C. albicans. The antibacterial and
      antimycotic activities of 5-6 are compared with several control drugs.

PMID- 9181691
TI  - Synthesis and cytostatic properties of 5-substituted derivatives of 3
      methylisoxazolo[5,4-d]1,2,3-triazine-4-ones and 3-methyl-5-triazene 4
      isoxazolecarboxylic acid ethyl esters.
AB  - Six new 5-substituted derivatives of 3-methyl-isoxazolo[5,4-d]1,2,3-triazine-4
      one and 3-methyl-5-triazene-4-isoxazolecarboxylic acid ethyl ester have been
      synthesized from 5-amino-3-methylisoxazole-4-carboxylic acid amides, and ethyl
      ester. They were examined for cytostatic activity in comparison with Dacarbazine.
      The 3-methyl-5-(4-chlorophenyl)isoxazolo[5,4-d]1,2,3-triazine-4-one showed better
      activity than Dacarbazine.

PMID- 9181692
TI  - Estimation of the size and directional output of functional groups of
      interneurons underlying abdominal positioning behaviors in crayfish.
AB  - Quantitative studies were made of a large population of interneurons that
      controls postural flexion and extension of the crayfish abdomen. The number of
      interneurons needed to produce a motor program was estimated by stimulating a
      single abdominal positioning interneuron and recording interneuronal activity
      that was evoked from rostral and caudal connectives in an isolated abdominal
      nerve cord. We also examined the role that these functional groups have in
      producing a stronger motor output in either a rostral or caudal direction and
      thus specifying various abdominal geometrics. The average number of interneurons
      responding to stimulation of a single abdominal positioning interneuron was 32
      (range: 3-50; n = 27). The average number of interneurons that decreased activity
      was 10 (range: 2-32). Of 653 activated interneurons from 20 preparations,
      approximately 43% fired between 2 and 5 Hz, 33% fired between 6 and 15 Hz, and
      25% fired > 15 Hz. The size of a recruited group was usually but not always
      correlated with the strength of its motor response or with the direction of motor
      bias. Therefore, the contribution of a group may depend upon the number of active
      elements as well as synaptic efficacy.

PMID- 9181693
TI  - Antiserum to the egg coats of the fat-tailed dunnart (Marsupialia, Dasyuridae)
      cross-reacts with egg coats of other marsupial and eutherian species.
AB  - We are examining the extracellular coats of the brush-tailed possum as a possible
      target for an immunocontraceptive vaccine for biocontrol of this pest species in
      New Zealand. In this study we have compared the composition of the extracellular
      coats of the fat-tailed and stripe-faced dunnarts, brush-tailed possum, domestic
      rabbit, and laboratory mouse using histochemistry, immunocytochemistry, and
      immunofluorescence. The histochemistry of the luminal epithelium of the oviduct
      and mucoid coats of the marsupials and rabbit indicated that they contain acidic
      glycoproteins. Immunofluorescence showed that polyclonal antiserum raised against
      the extracellular coats of the oocyte and early embryo of the fat-tailed dunnart,
      cross-reacted with the extracellular coats of the oocytes of all five species.
      These results suggest that there are common epitopes on the extracellular coats
      of oocytes and early embryos of distinctly related therian species. Further work
      to characterise these proteins is required to determine whether there is close
      homology between the oviductal glycoproteins of these species.

PMID- 9181694
TI  - Immunocytochemical detection and spatial distribution of myosin light-chain
      kinase in preimplantation mouse embryos.
AB  - As a follow-up to our previous study on the role of myosin light-chain kinase
      (MLCK), a Ca2+/calmodulin-dependent enzyme, in the development of preimplantation
      mouse embryos, we examined the presence and pattern of distribution of MLCK
      during preimplantation development of the mouse by whole-mount, indirect
      immunocytochemistry and by Western blotting, using a monoclonal antibody against
      MLCK. At all stages of preimplantation development, the nucleus was brightly
      stained with an unstained region around the nucleus, and regions near the cell
      membrane were also brightly stained. Using the optical sectioning capability of
      the confocal laser scanning microscope, we found that, up to the eight-cell
      stage, the regions of cell contact were mostly unstained, but along with the
      process of compaction, cell contact regions showed a clear staining pattern along
      with clearing of the cytoplasm. During formation of the blastocyst, a ring of
      immunofluorescence was found at the margin of the blastocoel. In the blastocyst,
      cells of the inner cell mass were less immunofluorescent than trophectoderm
      cells. These staining results appear to be due to specific immunoreaction between
      MLCK and the antibody, because the staining patterns were abolished when the
      antibody was preabsorbed by MLCK purified from chicken gizzard smooth muscle. In
      Western blotting of blastocysts, we found a band at 130 kD. We also show by
      immunoblotting and immunohistochemistry of various mouse tissues that the
      antibody used in this study has cross-reactivity to MLCK of various muscle and
      non-muscle tissues of the mouse. The presence and spatial distribution of MLCK at
      various stages of preimplantation development of the mouse suggest that it could
      play a crucial role in the regulation of the contractile events involved in the
      initial differentiation that occurs during formation of the mouse blastocyst.

PMID- 9181695
TI  - Characterization of a heat-stable fraction of lipovitellin and development of an
      immunoassay for vitellogenin and yolk protein in winter flounder (Pleuronectes
      americanus).
AB  - An enzyme-linked immunoabsorbent assay was developed for detection and
      quantification of the yolk protein lipovitellin (Lv) and its plasma precursor,
      vitellogenin (Vg), in winter flounder (Pleuronectes americanus). Native Lv was
      found to be a mixture of heat-stable and heat-labile molecules in mature,
      ovulated eggs. A heat-stable Lv fraction was purified from extracts of
      unfertilized eggs by brief heat treatment and gel permeation chromatography on
      Bio-Gel A-1.5. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) of heat-stable Lv revealed a single polypeptide of 94 kD, while native Lv
      also possessed several smaller polypeptides, suggesting that heat-labile Lv
      contains proteolytic cleavages of the 94-kD polypeptide which destabilize its
      structure. The Stokes radius of the native protein on Bio-Gel A-1.5 was estimated
      at 4.50 nm, while the Stokes radii of heat-stable and heat-labile Lv were 4.26 nm
      and 5.17 nm, respectively. Heat-stable Lv was used to produce a rabbit polyclonal
      antiserum which reacted with a single 175-kD polypeptide in Western blots of
      vitellogenic female winter flounder serum, but did not react with any component
      of male serum. Ouchterlony double diffusion using this antiserum demonstrated
      immunological identity of Lv, heat-stable Lv, and Vg. The anti-Lv anti-serum was
      used to construct an homologous ELISA with a linear response between 25 and 300
      ng/ml. This assay was used to characterize a Bio-Gel A-1.5 column profile of
      serum from an estradiol-treated male winter flounder, and a single peak, with
      Stokes radius of 6.70 nm, was identified as Vg. Winter flounder Vg was confirmed
      to be a dimer, while Lv from mature eggs was found to be a monomer of a lower
      molecular weight polypeptide.

PMID- 9181696
TI  - Involvement of a sperm protein sensitive to sulfhydryl-depleting reagents in
      mouse sperm-egg fusion.
AB  - Effects of various sulfhydryl (SH)-depleting reagents on sperm-egg fusion were
      demonstrated. When sperm were treated with three plasma membrane-permeable SH
      depleting reagents, N-ethyl-maleimide, sodium tetrathionate and 5,5'-dithiobis (2
      nitro-benzoic acid), the rates of cleavage of eggs were significantly lower than
      those with control sperm. Neither the motility, penetration of the zona
      pellucida, acrosomal status of the sperm, nor sperm-egg binding was affected by
      the SH-depleting reagents. Fusion of sperm and zona-free egg was estimated by the
      sperm nuclear incorporation into the eggs, intracellular calcium mobilization,
      and cortical granule exocytosis in the eggs. Sperm-egg fusion was blocked dose
      dependently when sperm were exposed to membrane-permeable SH-depleting reagents,
      but was not blocked by a membrane-impermeable SH-depleting reagent, eosin-5
      maleimide. Blockage of fusion by sodium tetrathionate was completely reversed by
      an SH-reductant, dithiothreitol. These results suggest that a protein which is
      sensitive to SH-depleting reagents may play an important role in mouse sperm-egg
      fusion and that the functional SH region of the protein may be located at an
      intracellular site.

PMID- 9181697
TI  - 2nd European Meeting on Pathogenesis and Host Response in Helicobacter pylori
      Infections. Galway, Ireland, March 23-25, 1997. Abstract.

PMID- 9181699
TI  - Commonwealth Caribbean Medical Research Council 42nd scientific meeting. St.
      Maarten, Netherland Antilles, April 16-19, 1997. Abstracts.

PMID- 9181698
TI  - National Scientific Medical Meeting. 11-12 April 1997. Abstracts.

PMID- 9181700
TI  - [Bacterial biofilms and resistance to disinfectants].
AB  - When bacteria grow in close association with solid surface, they constitute a
      microbial community tight included in the exopolymer glycocalyx. Many laboratory
      studies have shown that these bacteria are 10 to 100 folds more resistant to
      disinfectants than the bacteria of the same strain in suspension. Several factors
      are responsible for this resistance: the glycocalyx which limits the diffusion
      and reacts with the disinfectant, the more or less dense repartition of the
      bacteria inside the biofilm, their physiologic state with reduced metabolism, and
      the surface on which is the biofilm. The activity assessment of disinfectant
      agents is achieved with standardized methods. They must take into account not
      only the conditions in which the disinfectants are employed, but also the micro
      organism state. Experimental results showing the resistance of biofilm bacteria
      must lead to elaborate methods allowing the assessment of bactericide activity of
      disinfectants against biofilm bacteria.

PMID- 9181701
TI  - [Gender control and Olympics events from Albertville to Atlanta or good practices
      in gene biochemistry].
AB  - Gender verification in sport was introduced in 1967 based on the insufficient
      Barr test. For Albertville's Olympic Games we proposed the Medical Commission of
      IOC to carry out the control for the first time thanks to molecular biochemistry.
      PCR/SRY amplification is described giving more than 99.9% of good results. After
      Albertville, Barcelona and Lillehammer the method will be used in Atlanta and
      Nagano. Results and ethics are discussed. Easy and respectful of athletes, this
      reliable gender verification is indispensable for their protection. According to
      the good practices of CM/IOC, samples have to be discarded after the analysis is
      done.

PMID- 9181702
TI  - [Problems raised by the reformulation of inhalations after the removing of
      propulsors "chlorofluorocarbons" (CFC)].
AB  - The application of the Montreal convention which not only plans to remove CFCs
      from pressurized preparations but to stop also the production, will affect
      companies. However, for pharmaceutical use, antiasthmatic drugs are considered as
      essential and at the moment the use of CFCs is allowed. But if the production
      stops, a reformulation will be necessary. Three solutions are conceivable: The
      first one is to replace CFC 11, 12 and 114 with the old well known propellants as
      butane, isobutane, propane but they are not very compatible with pulmonary use.
      The second one is the use of new official substitutes as 134a (tetrafluorethane)
      or R227 (heptafluoropropane). The former is immediately available and can be used
      because its take of toxicity has been demonstrate by an international consortium,
      IPACT as well as the absence of action on ozone but a light "greenhouse effect"
      is expected. However, the simple substitution of CFCs for those two propellants
      is not easy due to their physical-chemical properties which are different from
      the old CFCs. This reformulation is so delicate that pharmaceutical companies
      have chosen a third solution: precompression pumps or clever devices which can
      deliver directly the pure drug in powder form. The other preparations to be used
      for dermatological or cosmetological uses have been reformulated since a long
      time with original and special presentation (bags in can or volatile solvents).

PMID- 9181703
TI  - [Antimicrobial activity of new pyridazine derivatives].
AB  - Continuing the investigations concerning synthesis-structure-biological activity
      in the pyridazine series, the results of the antimicrobial and antifungal tests
      of some new pyridazinium compounds are presented. The test was performed using
      the diffusimetric method with rustles steel cylinders based on the diffusion of
      the tested substances on the gelose surface. The comparative analysis of the
      obtained data leads to the following conclusions concerning the relation between
      structure and activity in the pyridazine series: 1. The cis-isomers are always
      more active comparatively with similar trans- isomers: 2. In the
      pyrrolopyridazine series we remark that the saturated or partial saturated
      compounds have always a stronger activity as the related aromatics derivatives.
      We also noticed that the saturated, partial saturated and aromatic compounds have
      different selectivity. Thus, the saturated are more active on the Pseudomonas
      aeruginosa and Candida albicans, the partial saturated are more active on the
      Staphylococcus aureus and Bacillus subtilis while the aromatic compounds are
      active on the Bacillus subtilis. 3. The influence of the Y-substitutes of para
      position of benzoylic radical and the substitutes of pyrrolo ring is not decisive
      towards activity, these affecting especially the selectivity.

PMID- 9181704
TI  - ["Medical devices and European regulations"].
AB  - In order to put on the European Market, the medical devices shall be in
      conformity with two European Directives transcribed in national regulation:
      Directive 90/385/CEE--20 June 1990: concerning the implantable active medical
      devices, mandatory since the 1/01/95; Directive 93/42/CEE--13 June 1993:
      concerning the medical devices, applicable since the 1/01/95 and mandatory the
      14/06/98. Both impose the conformity to essential requirements which can be
      proved by different procedures of evaluation verified by notify bodies. Then, the
      CE mark, technical passport, can be apposed. To demonstrate this conformity, the
      manufacturers can use harmonized european standards without obligation. The
      "Safety clause" allows to follow the "well-founded" of the CE marking and the
      national systems of vigilance to register and evaluate the incidents and to
      define corrective actions.

PMID- 9181705
TI  - [To prepare the future: analysis of the occupational changes in the dispensary
      pharmacist's profession. 2nd: Necessity of a common project linking the
      university and the chemist's shop: practical proposals].
AB  - After having in a first part established facts, the authors in a second part,
      would like the french pharmacy faculties to be more open to the profession. In
      order to reach this aim, at least one teacher per faculty must direct a research
      towards the assessment of professional practices by creating observatories in
      order to measure better what is going on in the field and consequently make the
      evolution in teaching possible. The author, a professor in clinical pharmacy, the
      latter being a discipline which is naturally open to professional practices,
      relates an original experiences carried out in Grenoble about the activity of a
      quality assurance centre for the pharmaceutical act.

PMID- 9181706
TI  - [To prepare the future: analysis of the occupational changes in the dispensary
      pharmacist's profession. 3rd: Reinventing the profession].
AB  - In this paper the author proposes a few tracks in order to reinvent the
      profession as a dispensing chemist and in order to regain a social credibility.
      This credibility, once based on the preparation of drugs with the know-how of the
      mortar-pestle, must be redefined in a society which is evolving which is
      organising so as to encourage all professionals towards a search for the quality
      of products and services. The author would like the university to evolve in a
      parallel direction and to contribute to the professional evolution by being party
      involved.

PMID- 9181707
TI  - [Hospital mortality in acute myocardial infarction: is it possible to predict
      using admission data?].
AB  - PURPOSE: To identify clinical variables on admission that are related to hospital
      mortality in acute myocardial infarction (AMI) and to generate a mathematic model
      to predict accurately this mortality. METHODS: Prospective study with 347
      consecutive patients with AMI in which clinical variables related to mortality
      were identified by univariate and multivariate analysis. The mathematic model
      generated by multivariate logistic regression analysis was applied in each
      patient to determine his/her probability (P) of hospital death. Model's accuracy
      was validated by reliability and discrimination tests. RESULTS: Admission
      variables directly and independently related to hospital mortality: female
      gender, age, absence of history of hypertension, history of previous infarction,
      non-inferior AMI and Killip class. These six variables, when present
      cumulatively, showed increasing mortality rates. Mean P value for non-survivors
      was significantly greater than for survivors (43.2 +/- 31.4% vs 9.1 +/- 12.5%, p
      < 0.00001). Reliability of the model to predict death, assessed by stratifying
      patients in three risk groups (low, medium and high) or continuously (by linear
      regression analysis) showed excellent predictive performance. Discrimination
      between survivors and non-survivors, assessed by C-index (concordance
      probability), disclosed 85% rate of success. CONCLUSION: Risk variables can be
      used in a mathematic model that is capable of predicting accurately in-hospital
      mortality of each patient with AMI. Mortality prediction can allow physicians to
      be more efficient in assessing risk-benefit ratios in these patients when faced
      with therapeutic decisions.

PMID- 9181708
TI  - [Influence of sustained increases of arterial pressure on left ventricular dP/dt
      when the left ventricular diastolic pressure is kept constant].
AB  - PURPOSE: To evaluate the influence of sustained elevations of arterial pressure
      on dP/dt values, while the left ventricular end diastolic pressure was kept
      constant. METHODS: Thirteen anesthetized dogs, mechanically ventilated and
      submitted to thoracotomy and pharmacological autonomic block (atropine-0.5 mg/kg
      i.v. + oxprenolol-3 mg/kg i.v.) were studied. The arterial pressure elevation was
      obtained by mechanical constriction of the descending thoracic aorta. Analyses
      were made in control (C) situation and after two successive increments of
      arterial pressure, sustained for 10 min, called hypertension 1 (H1) and
      hypertension 2 (H2), respectively. The end diastolic left ventricular pressure
      was kept constant by utilization of a perfusion system connected to the left
      atria. RESULTS: Heart rate did not change (C: 125 +/- 13.9 bpm; H1: 125 +/- 13.5
      bpm; H2: 123 +/- 14.1 bpm; p > 0.05); the LVSP increased (C: 119 +/- 8.1 mmHg;
      H1: 142 +/- 7.9 mmHg; H2: 166 +/- 7.7 mmHg; p < 0.01); the AoDP increased (C: 89
      +/- 11.6 mmHg; H1: 99 +/- 9.5 mmHg; H2: 120 +/- 11.8 mmHg; p < 0.01); the LVEDP
      (C: 6.2 +/- 2.48 mmHg; H1: 6.3 +/- 2.43 mmHg; H2:6.1 +/- 2.51 mmHg; p > 0.05) and
      the dP/dt (C: 3068 +/- 1057.1 mmHg/s; H1: 3112 +/- 995.7 mmHg/s; H2: 3086 +/-
      979.5 mmHg/s; p > 0.05) did not change. CONCLUSION: dP/dt values are not
      influenced by a sustained elevation of arterial pressure, when the end diastolic
      left ventricular pressure is kept constant.

PMID- 9181709
TI  - [Neonate and infant heart transplantation].
AB  - PURPOSE: Heart transplantation has offered children with complex congenital heart
      diseases and severe cardiomyopathies a chance for survival. The present article
      was written to show the three year experience of this procedure at the Instituto
      do Coracao-HCFMUSP. METHODS: The methodology used was based on heart transplant
      indication criteria, inclusion criteria for donors, postoperative management,
      immunosuppression and prophylaxis as well as treatment of potential
      complications. RESULTS: From November 1992 to November 1995, 11 children, aged 12
      days old to six years (mean 2.5 years) underwent transplantation. Sixty percent
      of recipients were male; weight ranged from 3.5 to 17.8 kg (mean 10.3 kg). The
      mean age of donors was 4.4 years (a range of three weeks to ten years), 80% male,
      weight ranging from 3.8 to 20 kg (median 14.3 kg). The survival rate was 91% and
      the remaining 10 children are doing well. The most important complications were
      systemic hypertension, acute rejection and infection. The number of rejections
      and infections per patient were 3.5 and 4.7 episodes, respectively. The follow-up
      was between one month to three years (average 16 months). CONCLUSION: In this
      experience, heart transplantation has given an additional opportunity for
      children with complex congenital heart diseases and cardiomyopathies, with a
      survival rate of 91% in three years.

PMID- 9181711
TI  - [Acute myocardial infarction occurring in a young man due to crack use].
AB  - The relation between cocaine use and cardiovascular disease has been well
      documented including coronary artery vasoconstriction, coronary thrombosis,
      accelerated atherosclerosis, myocarditis, cardiomyopathies and endocarditis.
      Cocaine use has reached epidemic proportions. Cocaine is the most commonly abused
      drug among young patients. We report the case of a 32-year-old male admitted to
      the emergency department with myocardial infarction secondary to an overdose of
      cocaine.

PMID- 9181710
TI  - [Acute embolic stroke treated with rt-PA during elective coronary angiography].
AB  - A 56-year-old female with unstable angina, presented an acute embolic ischaemic
      stroke of right medium cerebral artery during elective coronary angiography.
      Complete patency was achieved after an intraarterial infusion of rt-PA
      (60mg/60min) with important functional improvement.

PMID- 9181712
TI  - [Anatomoclinical correlations: case 3/96 (Department of medical clinic of
      Faculdade de Ciencias Medicas (UNICAMP))].

PMID- 9181713
TI  - [Effects of physical conditioning on ambulatory blood pressure monitoring in
      normotensive and hypertensive patients].

PMID- 9181715
TI  - [Pulmonary thromboembolism: clinical picture and diagnosis].

PMID- 9181714
TI  - [Optimization of the indications for and therapeutic management of patients
      referred for heart transplantation].

PMID- 9181716
TI  - [Acute pulmonary thromboembolism. Physiopathogenesis and use of thrombolytic
      agents].

PMID- 9181717
TI  - [Use of heparin and oral anticoagulants to prevent and treat deep venous
      thrombosis and pulmonary embolism].

PMID- 9181718
TI  - [Deep venous thrombosis. Prophylaxis].

PMID- 9181719
TI  - [Treatment of non-insulin-dependent diabetes mellitus. Current trends].

PMID- 9181720
TI  - [Role of the atrioventricular septum and mitro-aortic separation in the
      pathogenesis of fixed subaortic stenosis].
AB  - PURPOSE: To analyze, by cross-sectional echocardiography, morphological features
      of the atrial atrioventricular and ventricular septum potentially involved in the
      genesis of fixed subaortic stenosis. METHODS: Forty three children with fixed
      subaortic stenosis were compared with 86 normal children, matched by age, sex and
      body surface, and 43 children with congenital heart defects without fixed
      subaortic stenosis. RESULTS: The groups did not differ in as age, sex or body
      surface. The atrioventricular septum was significantly smaller in children with
      subaortic stenosis than in normal children or patients with other congenital
      heart diseases. The ventricular septum was significantly more aligned with the
      atrial septum in cases than in normal children and in patients with other
      congenital heart diseases. The odds ratio for the development of fixed subaortic
      stenosis was statistically significant in the presence of a short
      atrioventricular septum and with alignment of the ventricular and atrial septum,
      when analyzed in isolation or when controlled by perimembranous ventricular
      septal defect. CONCLUSION: It was concluded that in fixed subaortic stenosis the
      atrioventricular septum length is decreased and that this alteration may be a
      risk factor for its development.

PMID- 9181721
TI  - [Effect of enalaprilat on cardiotoxicity induced by doxorubicin].
AB  - PURPOSE: To evaluate whether the enalaprilat, an angiotensin converting enzyme
      inhibitor, was able to prevent the myocardial damage induced by doxorubicin
      (DOX). METHODS: Four groups composed of 10 Wistar rats each were followed for
      seven weeks: control (CONT); treated with enalaprilat (ENA, 1mg/kg/d/sc) treated
      with doxorubicin (DOX, 25 mg/kg/d/sc), and treated with doxorubicin plus
      enalaprilat (DOX+ENA). In eight animals of each group, the left ventricle (LV)
      was prepared for morphometric study and stained with HE and picro-sirius for
      identifying muscle fibers and collagen. In each group three fragments of the LV
      were examined with electronic microscopy (EM). For statistical analysis: the one
      way analysis of variance was performed and was followed by multiple comparisons
      test when the difference between groups were detected p values < or = 0.05 were
      considered significant. RESULTS: Light microscopy-it was not found any
      significant difference among the groups for muscle fibers patterns and proportion
      of collagen fibers of left ventricle. Electronic microscopy-the cristolysis index
      (proportion between normal and damage mitochondria) demonstrated significant
      difference between DOX and DOX+ENA groups (30.1 vs 11.6, p < or = 0.01).
      CONCLUSION: ENA prevented cardiotoxic alterations induced by DOX minimizing the
      aggression to the mitochondria and these findings, if confirmed in anima nobilis,
      may open a new clinical use for this type of drug.

PMID- 9181722
TI  - [Involvement of pulmonary function in patients treated with rotated chest muscle
      flap surgery for the treatment of sternal wound complications after heart
      surgery].
AB  - PURPOSE: To evaluate pulmonary function of patients submitted to muscle flap for
      treatment of mediastinitis. METHODS: Fifteen patients operated with the muscle
      flap technique were compared with 26 consecutive patients submitted to heart
      surgery with extracorporeal circulation, that did not present wound
      complications. Both groups were evaluated for age, sex, body weight, height,
      surgery, forced vital capacity (FVC), forced expiratory volume in first second
      (FEV1) and the relation (FEV1/FVC) in absolute and percentual values, espirometry
      conclusions and clinical evidences of lung disease. RESULTS: There was no
      statistical difference between preoperative and postoperative period for FVC (p =
      0.98), FEV1 (p = 0.68) and FEV1/FVC (p = 0.30) in the group with no sternal
      complications. In the control group, the median of FVC was 3907 +/- 1053.25 and
      in the study group was 2818 +/- 766.86 in absolute values (p = 0.0015). The
      median of FEV1, in the control group, was 2995 +/- 855.68 and in the study group
      was 2232 +/- 617.68 in absolute values (p = 0.0046). There was statistical
      difference, between groups, in FVC (104.78 +/- 21.73 and 82.04 +/- 21.16) and
      FEV1 (99 +/- 22.67 and 79.04 +/- 19.17) in percentual (p = 0.0026 and 0.0067)
      values. There was no statistical difference for the ratio FEV1/FVC. The study
      group had five patients diagnosed as having restrictive ventilatory insufficiency
      by espirometry against none in the control group (p = 0.0031). CONCLUSION:
      Patients with infectious complications of sternum and mediastinum, treated
      surgically with muscle flap rotation may present restrictive pulmonary
      insufficiency in moderate degree, that must be considered in this situation.

PMID- 9181723
TI  - [Tetralogy of Fallot associated with left atrial isomerism].
AB  - The association of tetralogy of Fallot with atrial isomerism has been rarely
      reported. Eight cases (five with left isomerism and three with right isomerism)
      are known. This paper reports two other cases of tetralogy of Fallot with left
      atrial isomerism. The syndrome's defects were disguised and without clinical
      expression because of the presence of the right ventricular outlet obstruction of
      tetralogy of Fallot. These diagnostic elements, not recognized in one of the
      patients previous to surgical correction of tetralogy of Fallot, were present:
      junctional rhythm, bronchial isomerism, partial anomalous pulmonary vein
      connection, agenesy of inferior vena cava and abdominal heterotaxy; their
      identification previous to surgical correction of tetralogy of Fallot, is
      necessary for an adequate surgical management.

PMID- 9181724
TI  - [Rheumatic heart disease and infective endocarditis in a patient with acquired
      immunodeficiency syndrome].
AB  - A 36-old-woman was admitted with an infectious syndrome, respiratory
      insufficiency and vasculitis. There was a history of chronic intravenous drug
      abuse, sexual promiscuity and rheumatic heart disease. She had HIV positive
      tests. The vasculitis and heart failure worsened and the patient died of stroke.
      At autopsy it was found histologic evidence of AIDS, rheumatic heart disease with
      Aschoff nodes, infective endocarditis with cerebral abscesses and thalamic
      infarction.

PMID- 9181725
TI  - [Cardiac granulomas due to Schistosoma eggs and endomyocardial fibrosis].
AB  - Evidences of a possible association between endomyocardial fibrosis and
      schistosomiasis have been recently investigated. We describe the finding of
      cardiac schistosomal granulomas in a 14 year-old-girl presenting symptoms and
      signals of right side endomyocardial fibrosis. Refractory ascistis and
      progressive atrioventricular block were observed during follow-up. Endomyocardial
      biopsy and post mortem specimens showed inflammatory infiltrates, schistosomal
      granuloma and fibrosis.

PMID- 9181726
TI  - [Nitric oxide and sepsis].

PMID- 9181728
TI  - [Endomyocardial fibrosis. Pathology].

PMID- 9181727
TI  - [Restrictions on the use of short-term action nifedipine in the United States. A
      review of facts].

PMID- 9181729
TI  - [Value of Doppler echocardiography in the diagnosis and management of
      endomyocardial fibrosis].

PMID- 9181730
TI  - [Endomyocardial fibrosis. Longitudinal follow-up of patients not treated with
      surgery].

PMID- 9181731
TI  - [Endomyocardial fibrosis surgery with atrioventricular valve preservation].

PMID- 9181733
TI  - [Genes, chromosomes and cancer].

PMID- 9181732
TI  - [Recurrence of fibrosis after endomyocardial fibrosis surgery].

PMID- 9181734
TI  - [Cytogenetic abnormalities as prognostic factors in acute myeloid leukemia].
AB  - The study of chromosomal abnormalities in AML has become very important in the
      diagnosis and in the characterization of subtypes since they are related to
      defined clinical, morphological and immunological features as well as treatment
      outcome and survival. PURPOSE: To evaluate the relative importance of cytogenetic
      abnormalities may have in AML patients. METHODS: 13 AML patients were studied
      during diagnosis. Cytogenetic study was performed on bone marrow aspirate
      material. RESULTS: M1 and M2 FAB subtypes were the most frequent (61.6%). The
      patients' median age was 38 years. Cytogenetic analysis showed abnormal karyotype
      in 61.5% of the cases and 15.3% of whom had abnormalities considered as good
      prognosis [t(15;17) and t(8;21)]. At the evaluation day there were 3 patients
      alive, two in continuous complete remission and 1 in a second remission. The
      median total survival time was 7 months. Patients were divided into two groups: a
      "good prognosis" one, that joined 5 patients with normal karyotype and 2 with the
      translocations t(15;17) and t(8;21) and another, the "bad prognosis" one, with 8
      patients with unfavorable chromosomal abnormalities. The good prognosis group had
      a median survival time of 9 months versus 6.2 months in the other, but this was
      not statistically significant (p = 0.18), probably owing to the small number of
      cases in the groups. But when one observes the cases separately see that patients
      with translocations (8;21) and (15;17), known as good prognosis, had longer
      survivals. CONCLUSION: The different survival time between the two groups showed
      the importance of cytogenetic study to distinguish the patient who will have
      favorable evolution.

PMID- 9181735
TI  - [Central venous catheter-related infections in critically ill patients].
AB  - BACKGROUND: To determine incidence rate, etiology and risk factors for central
      venous catheter (CVC)-related infections in critically-ill patients, a
      prospective cohort study was conducted in the general Intensive Care Unit (ICU)
      of a 212 bed Hospital in Florianopolis, Brazil. MATERIAL AND METHOD: Patients
      admitted to ICU between May 1993 and February 1994, exposed to short-term CVC,
      were included in the study. Quantitative skin culture at CVC insertion site, semi
      quantitative CVC tip culture, quantitative hub culture, and peripheral blood
      culture were done. Results were submitted to univariate and multivariate
      analysis. RESULTS: Fifty-seven catheterization periods were analysed in 51
      patients. The incidence rate was 21.1% (33.1 per 1,000 catheter-days) for local
      infection, and 8.7% (14.1 per 1,000 catheter-days) for catheter-associated
      bacteremia. The skin at the insertion site was colonized in 32.7% and the hub in
      29.1% of the patients respectively. Potential sources of infection were the skin
      in 41.2% of the cases, the hub in 29.4%, remote site in 5.9% and unknown in
      23.5%. The hub was implicated in 60% of the catheter-associated bacteremias.
      Coagulase-negative staphylococci were the main isolates. Another intravascular
      device and purulence at the insertion site were independently associated with
      local infection. Insertion at internal jugular site and hub colonization were
      independently associated with bacteremia. CONCLUSIONS: Catheter-associated
      bacteremia is a major complication of central venous catheterization in
      critically-ill patients. Internal jugular insertion and CVC hub colonization are
      important risk factors for significant catheter-related infections.

PMID- 9181736
TI  - [Nutritional and metabolic support in the pediatric ICU].
AB  - Nutritional support has been considered an important part of the treatment of
      critically ill patients. The information about the current clinical pattern of
      nutrition support in hospitals may provide a basis for future modification and
      improvement of its prescription and use. OBJECTIVES: 1) To evaluate patterns of
      usage and monitoring of nutritional support in critically ill children; 2) To
      recommend policies aiming at the improvement of the nutritional support quality.
      PATIENTS AND METHOD: Records of 37 patients receiving nutritional support
      throughout one year were reviewed. RESULTS: From a total of 425 days of therapy,
      the single parenteral route was utilized in 80.50% the digestive route (tube
      feeding or oral route) in 19.5% of this time. A previous nutritional assessment
      was performed in 3 children; no patient had the nutrition goals set. The nitrogen
      to nonprotein calories ratio ranged between 1:80 and 1:250. Only 29.7% of the
      patients had their estimated caloric needs supplied and this goal was achieved
      only in those patients who were on enteral tube feeding. Patients did not
      achieved their goals for vitamins. The supply of oligoelements was adequate
      except zinc. Nutritional monitoring parameters including weight, serum albumin
      and serum triglycerides were performed in almost all the patients but without
      uniformity. CONCLUSION: There was a lack in the implementation of nutritional
      support. Inadequacy of protein and micronutrients supply, irregular nutritional
      monitoring and infrequent enteral feeding were detected. A minimal standard for
      nutritional and metabolic monitoring and the organization of a multidisciplinary
      team in charge of coordinating the providing of nutritional support are
      suggested.

PMID- 9181737
TI  - [Psychiatric diagnosis and physician-patient relations].
AB  - The author emphasizes the importance of diagnosis as a medical procedure. A brief
      history of Psychiatry development and of the psychiatric diagnosis in order to
      characterize it as multiple and to comment its systematization paying special
      attention to Leme Lopes point of view. The current predominance of non
      theoretical classifying systems concerning etiology and, paradoxically, of more
      and more advanced resources in the causal diagnostic is pointed out. The author
      also stands out the recognition of the tensions generated by the medical studies,
      which may contribute to the complexity of the diagnostic procedures and to the
      damage of the development of the doctor-patient relationship as well as the
      therapeutic purpose of Medicine and Psychiatry.

PMID- 9181738
TI  - [Phototherapy, photochemotherapy, and various photosensitizers].

PMID- 9181740
TI  - [When should liver transplant be indicated in the treatment of alcoholic hepatic
      disease?].

PMID- 9181739
TI  - [Hantavirus disease].

PMID- 9181741
TI  - [The role of endoscopy in the diagnosis and treatment of pancreatic diseases].

PMID- 9181742
TI  - [Congenital splenic cyst in a child: therapeutic possibilities].

PMID- 9181743
TI  - [Long-term survival in patient with acquired immunodeficiency syndrome and
      adenocarcinoma of the lung].
AB  - BACKGROUND: Lung cancer associated with acquired immunodeficiency syndrome (AIDS)
      is unusual. Literature review between 1984 and 1993 showed less than 100
      published cases of this association. From those cases it appears that the
      neoplasia is more aggressive and survival after diagnosis is less than 12 months.
      A case is reported of an HIV positive man with adenocarcinoma of the lung that
      survived 28 months after diagnosis, the longest published survival in such case
      described in the medical literature. CASE REPORT: A 57-year old Caucasian
      homosexual male and heavy smoker was diagnosed as having a bronchogenic carcinoma
      and underwent right upper lobectomy, chemotherapy, thoracic surgery for carcinoma
      recurrence and radiotherapy. He remained in good condition with reasonable life
      quality and died for reasons unrelated either to his tumor or the antineoplastic
      treatment. CONCLUSIONS: Diagnostic delay and the immuno-deficiency are the
      reasons for the dismal prognosis of lung cancer in AIDS patients. Aggressive
      treatment of the neoplastic disease should be done in such cases, as reasonable
      prolonged survival is possible, as shown by our report.

PMID- 9181744
TI  - Tumor necrosis factor receptor: Fc fusion protein does not improve septic shock
      and may increase mortality in human.

PMID- 9181745
TI  - Transvaginal ultrasonography assessment of ovarian volumes in postmenopausal
      women.
AB  - The authors evaluated ovarian volumes by transvaginal ultrasonography at
      different periods after menopause. Ninety-eight postmenopausal women with an
      average age of 51.9 years and a one- to eight-year postmenopausal period were
      studied. The control group consisted of 40 women during menacme with an average
      age of 31.8 years, who were also submitted to transvaginal ultrasonography to
      evaluate ovarian volume. There was no significant difference between right and
      left ovarian volumes in the study groups. There was a significant decrease in
      measure and standard deviations of the volumes after the first year of menopause
      (mean volume--2.2 +/- 0.9 cm3) when compared to the control group (mean volume-
      6.3 +/- 2.0 cm3), followed by a slow and gradual shrinking after this phase.
      Decrease in ovarian volume became significant after the fourth postmenopausal
      year. Transvaginal ultrasonography demonstrated great importance as an
      investigative method of ovarian diseases in postmenopausal women.

PMID- 9181746
TI  - Nutritional and metabolic assessment of critically ill children.
AB  - In a prospective study, with the objective of determining the metabolic profile,
      response to nutrient supply, and role of nutritional and metabolic assessment
      parameters in children admitted to a pediatric ICU, 11 patients in the age group
      2-12 were studied. The assessment was carried out during the first 72 hours of
      admission, and again seven days later, and included the following parameters;
      caloric supply; nitrogen supply; prealbumin serum level; urinary urea nitrogen;
      nitrogen balance and creatinine-height index. The evolution of the parameters in
      the two stages of the study showed the following results: The urinary urea
      nitrogen median value at admission was 7.5 g/m2 of corporeal surface, and did not
      present significant changes seven days later. There was a significant increase in
      caloric supply from 42.9 to 70.3 kcal/kg, and in nitrogen supply, from 4.7 to
      10.2 g/m2 of corporeal surface p 0.01. The level of nitrogen balance rose from 
      5.6 to 2.5 g/24 h (p < 0.03), and that of prealbumin, from 16.7 to 26.3 mg/dl (p
      < 0.03). There was a significant reduction in the creatinine-height index, from
      86.2 percent to 55.0 percent p 0.01. The magnitude of urinary urea nitrogen
      excretion at admission varied 2.5-13.8 g/m2 of corporeal surface. Based on this
      parameter, it was not possible to establish a characteristic metabolic profile
      for the conditions studied. Notwithstanding an increase in the protein and
      caloric supply, prealbumin level and nitrogen balance observed in the second
      stage of the study, the patients lost muscle mass and entered into a malnutrition
      process, probably due to intense protein catabolism and the poor response to
      nutrition supply that occurs in metabolic stress.

PMID- 9181747
TI  - Angyomatous vocal polypus--a complete spontaneous regression.
AB  - The authors describe a male patient who had malignant lymphoma seven years ago
      which remitted with chemotherapy. Two years ago he developed dysphonia. An
      unilateral, pediculate smooth red lesion on the right vocal fold was later
      discovered. Even without benefit of medicamentosus treatment, the patient refused
      surgery. In a reevaluation using rigid telescopy of the larynx two years later,
      the lesion had disappeared, completely and spontaneously. As there are no
      existing publications on this topic, this case report is an alert that surgery
      should be recommended with extrema caution in this type of vocal disease.

PMID- 9181749
TI  - Ultrastructural aspects of the remodeling process of the Corpus albicans in the
      recent postmenopausal period.
AB  - To study the cytophysiology of the corpus albicans in the recent postmenopausal
      period, the authors analyzed the ovarian ultrastructure of ten patients submitted
      to oophorectomy due to non-malignant gynecological diseases. Evidence of a
      remodeling process with connective tissue substitution of the corpora albicantia
      was observed. The remodeling process appears to depend on the activity of three
      essential cell types; the fibroblasts, which provide collagen synthesis; the
      macrophages, which phagocytize the flaky material; and the myofibroblasts, mainly
      located in the peripheral region of the corpora albicantia, which may have a
      retracting action on the remodeling site of the corpus albicans.

PMID- 9181748
TI  - The progestogen challenge test in postmenopausal women: clinical and morphologic
      aspects.
AB  - The clinical aspects and anatomopathological patterns of 150 postmenopausal women
      were studied using the progestogen challenge test. An endometrial biopsy was
      obtained and submitted to the progestogen test. A histopathological analysis of
      the uterine mucosa from women with a positive progestogen test revealed that the
      endometrium was active in 44 percent of cases and atrophic or inactive in 56
      percent. In contrast, among women with a negative response, the endometrium was
      atrophic in 94 percent of cases and active in 6 percent. Analysis of clinical
      aspects did not show significant differences between groups in terms of age; age
      at menarche and at menopause; fasting blood glucose levels; or body mass.
      However, postmenopausal time was significantly shorter for women with a positive
      test, with a correlation between postmenopausal time of one to two years and test
      positivity. The progestogen challenge test for the detection of atrophic
      endometrium presented 78.57 percent sensitivity, 77.05 percent specificity, 44
      percent positive predictive value, and 94 percent negative predictive value.
      Thus, when negative, the test is highly valuable, indicating the presence of
      atrophic endometrium in 94 percent of cases. False-negative results occurred in
      only 6 percent of the subjects, with no case of hyperplasia detected. However,
      when the response to the test was positive, the endometrium was atrophic in 56
      percent of the cases. We suggest that, in order to avoid invasive procedures, the
      progestogen challenge test be combined with other methods such as transvaginal
      ultrasonography.

PMID- 9181750
TI  - HTLV-I infection and adult T-cell leukemia in Brazil: an overview.
AB  - Human T-cell lymphotropic Virus Type I (HTLV-I) is the etiologic factor for adult
      T-cell leukemia/lymphoma (ATL). HTLV-I infection can also lead to other diseases,
      such as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP),
      uveitis, arthropathy and infectious dermatitis. Studies of the infectious mode of
      transmission of HTLV-I and risk factors for HTLV-I-related diseases have been
      conducted in several countries, and differences in the prevalence, age patterns,
      ethnic groups and clinical presentation of the related diseases have been
      described worldwide. Based on the geographical characteristics of Brazil and data
      from the literature, we have summarized the distribution of seroprevalence in
      blood donors in different states around the country, as well as the incidence of
      ATL in regards to the endemic foci. ATL in Brazil has the same characteristics as
      those described elsewhere, but is reported more frequently at a younger age. In
      order to better evaluate ATL in Brazil, a registry has been established at the
      several hematologic centers under the sponsorship of the instituto Nacional de
      Cancer and the Brazilian Society of Hematology and Hemotherapy, for the purpose
      of recording all cases originally diagnosed in Brazil.

PMID- 9181752
TI  - Evidence based medicine is the conscientious, explicit, and judicious use of
      current evidence in making decisions about the care of individual patients.
AB  - The 2nd U.K. Workshop on Evidence Based Health Care, London, 11th-16th February
      1996, with Dr. Trisha Greenhalgh (UCLMS) as co-ordinator, and Prof. David Sackett
      (Oxford), as orientator, constituted an important meeting to disseminate EBHC in
      UK and Europe. "Evidence Based Medicine is the conscientious, explicit, and
      judicious use of current best evidence in making decisions about the care of
      individuals patients" (Sackett, 1996). The methodology utilized was Problem-Based
      Learning (PBL), with small groups sessions with tutor and co-tutor as
      facilitators of the discussion process. The participants have been demonstrated
      that it's possible to teach EBHC using different strategies, approaches and
      resources. This Workshop was an excellent opportunity not only to share and
      receive informations about Clinical Epidemiology, Biostatistics and EBHC, but
      also to participate in a "learning to learn" active process to understand how to
      teach and learn EBHC.

PMID- 9181751
TI  - HIV heterosexual transmission to stable sexual partners of HIV-infected Brazilian
      hemophiliacs.
AB  - Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual
      partners were studied with the aim of assessing the rate of HIV transmission in
      this at risk group. The mean length of relationship between couples was 7.4
      years. The hemophiliac men were Class II (n = 6), III (n = 11) and IVa (n = 2) of
      the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers;
      five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine
      and confirmatory tests, a prevalence similar to that seen in other countries.
      They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive
      women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values
      and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+
      numbers, except for elevated CD8+ cells in three of them, but immune
      abnormalities had already been seen in some seronegative partners at high risk
      for HIV infection. Our results reinforce previous suggestions that heterosexual
      transmission to stable female partners occurs preferentially early after
      initiation of sexual exposure, and possibly when the transmitter had high levels
      of viremia and regular sexual activity.

PMID- 9181753
TI  - Soluble markers of endothelial cell function.
AB  - Damage to the endothelium is believed to be important in the development and
      progression of atherosclerosis. Consequently, vascular biologists are seeking
      good markers of endothelial cell function which hope to provide tools to dissect
      the role of these cells in disease. This review will examine a number of
      endothelial cell products (thrombomodulin, von Willebrand factor and soluble E
      selectin) and discuss their value as markers of vascular integrity.

PMID- 9181754
TI  - Haemostatical and rheological aspects of dysfibrinogenemia.
AB  - Congenital dysfibrinogenemia is based on different alterations in the structure
      of the fibrinogen molecule leading to a variety of disturbances in the clotting
      process. Clinical manifestations of the disorder are showing a wide range from
      asymptomatic states to mild bleeding diathesis as well as thrombotic
      complications. In this study two of the 14 patients with dysfibrinogenemia showed
      a history of mild bleeding while the others showed no clinical symptoms. As
      fibrinogen is also an important factor of the blood fluidity not only haemostatic
      but also rheological parameters were measured. Included in the study were 14
      patients with ascertained dysfibrinogenemia in comparison to 11 non-affected
      relatives and a control group of 297 apparently healthy subjects. Plasma
      viscosity (p < 0.0001) and erythrocyte aggregation index (p < 0.00001) were
      significantly higher in the patients than in their healthy relatives and the
      control group. A pathologically increased erythrocyte aggregation was found in 10
      of the 14 patients but only in 1 of the 10 relatives. The dysfunction of the
      fibrinogen molecule thus influences the aggregation process of the red blood
      cells to a greater extent than normal fibrinogen. Moreover, there seems to be a
      stronger influence of the dysfunctional fibrinogen molecule on the aggregation
      process than on plasma viscosity. To date the question if the enhanced
      erythrocyte aggregation in dysfibrinogenemic patients may be of any diagnostic
      interest and if there are significant differences between patients with bleeding
      diathesis and thrombophilia cannot be answered and remains to be cleared in
      further investigations.

PMID- 9181755
TI  - Compensatory and adaptive changes in microcirculation and left ventricular
      function of patients with chronic iron-deficiency anaemia.
AB  - The severity of alterations in the microcirculatory bed and the incidence rate of
      myocardial dysfunction in 299 female patients with differently severe iron
      deficiency anaemia (IDA) as a mechanism of compensation and adaptation towards
      chronic anaemic hypoxia was investigated. Significant changes, mainly in the
      venular and capillary part of the microcirculatory bed in conjunctival
      biomicroscopy were observed. An increased diameter and a decreased linear density
      of the venules along with microcongestion foci, microhaemorrhages, an enhanced
      undulation and irregularity of both venules and capillaries and a 'sludge
      phenomenon' were demonstrated. Echocardiographically, a significant enlargement
      of telediastolic and telesystolic dimensions and volumes of the left ventricle, a
      hyperdynamic working regimen of the heart with increased cardiac output and
      stroke volume were observed with advancing severity of IDA and microcirculatory
      alterations. A slight reduction of myocardial contractility was found only in the
      cases with a severe degree of anaemia. The treatment performed with parenteral
      iron induced a complete reversibility of both myocardial and microcirculatory
      changes with the moderate and slight degree of IDA while there was a delayed
      reversibility concerning normalization of the values of haemoglobin and serum
      iron that required a more prolonged follow-up of these patients.

PMID- 9181756
TI  - New evidence for involvement of blood rheological disorders in rise of peripheral
      resistance in essential hypertension.
AB  - To ascertain the contribution of blood rheological disorders in elevation of
      arterial pressure during hypertension, erythrocyte aggregability was investigated
      in rats and evaluated in patients with the Georgian technique. The evidence
      obtained for the significant role that blood rheological disorders play in
      development of this pathological phenomenon was found to be as follows: (a) the
      enhanced erythrocyte aggregation in rat's blood (caused by high molecular weight
      dextran administration) results in a rise of the systemic arterial pressure while
      the arteriolar diameters remain unchanged; (b) a direct relationship has been
      found between the index of erythrocyte aggregability (Georgian technique) and
      total peripheral resistance in patients with mild and severe forms of the
      essential hypertension; and (c) a linear relationship between lowering of
      erythrocyte aggregability and the diastolic arterial pressure, as well as total
      peripheral resistance, was revealed also following treatment of hypertensive
      patients with Ca-antagonists. These findings support the conclusion that blood
      rheological disorders, related to increased erythrocyte aggregability, play a
      significant role in the concerted action of factors enhancing peripheral
      resistance and in elevation of the arterial pressure in patients with essential
      hypertension.

PMID- 9181757
TI  - Rheological changes in hypertensive patients treated with ramipril.
AB  - This study was designed to characterize blood viscosity changes in 13 patients
      with mild to moderate diastolic hypertension treated with ramipril monotherapy
      for three months. The ramipril dose was titrated from 2.5 to 20 mg daily to
      achieve a diastolic blood pressure of less than 90 mm Hg. All patients received a
      stable dose of ramipril for three months. Viscosity measurements were made at 37
      degrees C with the Mettler Contraves LS-40 microviscometer. Fibrinogen was
      determined by the Clauss method by averaging three separately acquired plasma
      samples. The systolic blood pressure (mean +/- standard deviation) was lowered
      from 141.2 +/- 9.1 to 129.2 +/- 11.2 mm Hg (p = 0.005) and the diastolic blood
      pressure was lowered from 95.2 +/- 4.9 to 84.2 +/- 7.3 mm Hg (p = 0.0001). In 13
      patients with mild to moderate diastolic hypertension, blood pressure reduction
      with ramipril was accompanied by no significant changes in blood viscosity,
      plasma viscosity, serum viscosity or fibrinogen.

PMID- 9181758
TI  - Serum zinc and blood rheology in sportsmen (football players).
AB  - We aimed at investigating relationships between zinc status, blood rheology and
      blood glucose during exercise. Twenty-one professional football players underwent
      a triangular maximal exercise test on cycloergometer, with progressively
      increasing work loads until VO2max. On the whole these subjects had a low serum
      zinc because nine of them had a hypozincemia (0.54 +/- 0.01 mg/l) which suggested
      a zinc deficiency. Subjects with low serum zinc were able to perform a lower
      power output (123 +/- 8.71 vs. 166.27 +/- 14.84 watts, p = 0.029) and exhibited a
      higher increase in blood lactate during exercise (7.51 +/- 0.81 vs. 5.57 +/- 0.33
      mmol/l, p = 0.024) resulting in a lower 2 mmol lactate threshold (44.7 +/- 3.9%
      vs. 58.9 +/- 4.8% of maximal power output, p = 0.04). They were less able to
      maintain their plasma glucose and exhibited a tendency towards hypoglycemia (p =
      0.0153). Hypozincemia was associated with a higher viscometric RBC rigidity index
      (p = 0.0009), and this index was negatively correlated to serum zinc (r = -0.68,
      p = 0.7 x 10(-3)). Blood viscosity at high shear rate (MT90 viscosimeter)
      corrected for hematocrit (45%) remained higher during exercise in these
      hypozincemic subjects (p = 0.003). This study suggests that zinc status may
      influence blood rheology during exercise, either by its direct action on RBC
      flexibility (demonstrated in vitro) or by its effect on lactate accumulation
      which may in turn modify erythrocyte fexibility.

PMID- 9181759
TI  - Low-dose intermittent urokinase therapy in chronic symptomatic end-stage arterial
      disease--clinical relevance for patients with coronary artery disease or
      peripheral arterial occlusive disease.
AB  - Symptomatic end-stage arterial disease in coronary artery or peripheral arterial
      occlusive disease represents an increasing clinical problem as cardiovascular
      mortality in these patient groups has declined due to improved secondary
      prevention. While in peripheral arterial occlusive disease amputation with
      subsequent life-long physical disability is the major problem, patients with end
      stage coronary artery disease and refractory angina pectoris repeatedly report to
      the emergency ward with the clinical symptoms of unstable coronary syndromes, but
      myocardial infarction is generally ruled out. For these patients long-term
      intermittent urokinase therapy has been developed as an alternative treatment
      modality. Potential mechanisms for clinical effectiveness include improvement of
      rheological blood properties, thrombolysis of non-occluding arterial thrombi and
      possibly plaque regression. In coronary artery disease urokinase is applied as an
      intravenous bolus injection of 500,000 IU urokinase three times a week over a
      period of 12 weeks. This leads to a marked reduction of fibrinogen by about 35%
      and of clinical symptoms by around 70% accompanied by a reduction of exercise
      induced myocardial ischemia. In observational studies in patients with peripheral
      arterial occlusive disease injections of 500,000 IU of urokinase were usually
      given daily for a shorter time period of three to four weeks with a clinical
      success rate, defined as a cessation or marked reduction of rest pain and/or
      salvage of a limb, of around 50%. Given the state of critical ischemia in both
      entities of atherosclerotic disease, long-term intermittent urokinase therapy
      represents a promising antiischemic approach. In particular in patients with
      peripheral arterial occlusive disease randomized controlled trials with prolonged
      treatment periods, which are likely to improve clinical results, are warranted.

PMID- 9181760
TI  - Neonatal whole blood hyperviscosity: the important factor influencing later
      neurologic function is the viscosity and not the polycythemia.
AB  - The neurologic outcome of 23 seven-year old children who had cord blood
      hyperviscosity was compared with that of children with normal cord blood
      viscosity in a randomised, controlled and blinded study. Viscosity was measured
      using a coaxial narrow-gap couette viscometer. Sixteen (69.6%) of the children
      with hyperviscous cord blood had a disability; this incidence being three times
      greater (22.7%) than in children whose cord blood was not hyperviscous (P <
      0.01). In three children with cord-blood hyperviscosity, the disability was
      severe. No child had a severe disability with normal cord blood viscosity. Of the
      eight children whose cord blood was hyperviscous, but not polycythemic, six
      (75.0%) had a disability and in one child the disability was severe. These
      results demonstrate an association between cord blood hyperviscosity and later
      neurologic development. Cord studies are non-invasive and result in the rapid
      diagnosis of the neonatal hyperviscosity syndrome, so allowing earlier treatment.
      This may be crucial in altering the effects of hyperviscosity on the developing
      brain in the early neonatal period. Because the neurologic outcome of children
      was similar whether polycythemia was present or not, the prime factor was the
      viscosity and not the hematocrit level. We suggest it may be necessary to perform
      cord blood viscosity studies routinely.

PMID- 9181762
TI  - Radiotherapy for Cancer. Summary.

PMID- 9181761
TI  - Pharmacological preconditioning of ischaemia.
AB  - Five repeated submaximal treadmill exercises at 2 h intervals following a maximal
      test prolong walking distance and reduce haemorheological derangement in a second
      maximal test in patients affected with peripheral obliterative arterial disease
      (POAD). An increase in adenosine plasma levels is observed during maximal tests,
      thus suggesting the possibility of an ischaemic preconditioning of lower limbs.
      The intravenous infusion of 50-100-200 mg buflomedil, and the oral administration
      of 300-600-900 mg of the drug in POAD patients, also produce an increase in
      plasma levels of adenosine. Finally, 600 mg buflomedil orally at 12 h intervals
      produced pulse increase in adenosine plasma levels without any accumulation of
      the drug or adenosine for at least one week. The possibility of a pharmacological
      preconditioning of ischaemia is suggested.

PMID- 9181763
TI  - Inadequate cerebral perfusion is an unlikely cause of perioperative stroke.
AB  - The purpose of this study was to determine the importance of hypoperfusion
      ischemia as a cause of stroke during carotid endarterectomy (CEA). A
      retrospective analysis of 128 consecutive CEA procedures were examined in
      patients at risk for hypoperfusion ischemia, namely, patients with occlusion of
      the contralateral carotid artery. All procedures were performed under general
      anesthesia without the use of a temporary indwelling shunt. Sixty-one percent of
      patients had cerebrovascular symptoms preoperatively and 39% were asymptomatic.
      The degree of stenosis of the carotid artery was 80%-99% in 67% (86/128) of
      patients, 60%-79% in 25% (32/128), 20%-59% in 7% (9/128), and 0-19% in 0.8%
      (1/128). The perioperative mortality was 0.8% (1/128), the incidence of permanent
      neurologic morbidity was 1.6% (2/128), and the incidence of transient neurologic
      morbidity was 3.9% (5/128). In conclusion, these data suggest that hypoperfusion
      ischemia is a rare cause of stroke during CEA even in patients with occlusion of
      the contralateral carotid artery and that CEA can be performed safely even in
      patients with contralateral occlusion without the use of a temporary indwelling
      shunt.

PMID- 9181764
TI  - Is carotid endarterectomy justified in patients with severe chronic renal
      insufficiency?
AB  - We evaluated the effect of chronic renal insufficiency (CRI) and commonly
      associated co-morbid conditions on the risk of adverse events (stroke, cardiac
      events, and death) within 30 days after carotid endarterectomy (CEA). Renal
      function of patients undergoing CEA from 1980 to 1994 was categorized as normal
      (creatinine < 1.5 mg/dl), mild CRI (creatinine 1.5-2.9 mg/dl), or severe CRI
      (creatinine > 2.9 mg/dl). Renal function, age, gender, indications for surgery,
      cardiac disease, chronic preoperative hypertension, diabetes mellitus, smoking
      history, severe perioperative hypertension or hypotension, intraoperative
      shunting, and patch closure of the carotid artery were evaluated for their
      influence on the incidence of adverse events within 30 days after surgery. The
      timing of postoperative stroke and mechanism of stroke was determined when
      possible. A total of 237 patients underwent 285 CEAs. No significant differences
      were found in demographic or clinical characteristics between patients with
      normal or abnormal renal function. Postoperative stroke and death occurred
      following three (43%) of seven CEAs in six patients with severe CRI,
      significantly greater than the 6% incidence of stroke and 1% mortality following
      264 CEAs in 221 patients with normal renal function (p < 0.001 and p < 0.001,
      respectively). Of three patients with severe CRI suffering postoperative stroke,
      two had severe, difficult to control perioperative hypertension. Two patients
      with severe CRI who survived 30 days after operation suffered strokes 3 and 4
      months postoperatively with one stroke-related death and another death not
      directly related to the stroke. One patient with severe CRI who survived CEA
      without stroke was alive 6 months after surgery. The 0% incidence of stroke and
      death following 14 CEAs in 10 patients with mild CRI was not significantly
      different from that in patients with normal renal function. Postoperative stroke
      was not associated with age, gender, history of cardiac disease, chronic
      preoperative hypertension, diabetes, smoking, or use of intraoperative shunts or
      patch closure. All three cardiac events occurred in diabetic patients, although
      they constituted only 26% of operations (p = 0.003). Other clinical
      characteristics were not associated with the occurrence of cardiac events.
      Patients with severe CRI are at significantly greater risk than others for
      postoperative stroke and death following CEA, possibly related to difficulty
      controlling severe perioperative hypertension. Age, gender, smoking, preoperative
      hypertension, diabetes, and known cardiac disease are not associated with an
      increased risk of postoperative stroke in any patient group. CEA can be justified
      only for carefully selected patients with severe CRI who have symptomatic carotid
      disease, acceptable operative risk factors, and a good long-term life expectancy.
      CEA in patients with mild CRI is associated with low risk, and these patients may
      be treated with the same consideration as patients with normal renal function.

PMID- 9181766
TI  - Incidence and pathophysiologic significance of infected carotid artery plaque.
AB  - It is unknown whether an association exists between infectious microorganisms and
      atherosclerosis. Eighty consecutive patients undergoing carotid endarterectomy
      were studied to detect for bacterial or virus infections in removed carotid
      atherosclerotic plaques. Twenty-one patients (25%) were found to have positive
      cultures for bacteria of the carotid plaques. Three patients (4%) did not have
      bacterial contamination of controlled cultures of the skin. Of these three
      patients, two grew diptheroids and one grew staphylococcus. The control cultures
      of the skin demonstrated that 25 patients (31%) grew diphtheroids and 29 (36%)
      grew staphylococcus. Five patients grew both organisms. There was no evidence of
      colonization within the atheromatous plaque material in histologic studies of the
      three patients that had positive cultures of their plaque. All viral cultures
      were negative. The positive carotid cultures found were most likely due to
      contamination from the skin. This study demonstrates the unlikelihood of
      bacterial or virus infections as either an etiologic or a pathogenetic factor in
      carotid artery atherogenesis.

PMID- 9181765
TI  - The elongation of the internal carotid artery: early and long-term results of
      patients having surgery compared with unoperated controls.
AB  - The purposes of this study are to (1) demonstrate the association of elongations
      of the internal carotid artery (ICA), that is, kinking, coiling, tortuousity, and
      angulation, and the neurologic symptoms with high stroke risk; (2) compare the
      results of the surgical treatment versus the medical treatment alone; (3)
      contribute to the knowledge of the natural history of these anatomical
      particularities. From January 1992 to December 1994, 113 patients with ICA
      kinking, coiling, tortuousity, and angulation were randomized either to surgery
      (group I, n = 55) or not (group II, n = 58). Patients, who presented a carotid
      hemodynamically significant lesion (>60%) at the origin and associated distal
      elongation were excluded. The groups were comparable with regard to sex, age,
      risk factors for atherosclerosis, associated diseases, symptoms and anatomic
      feature of the contralateral ICA. Follow-up was obtained in all patients: it
      consisted of clinical evaluation and Duplex scan control at 3-month intervals
      during the follow-up period (6-36 months; average, 23). Histologic specimens were
      obtained in all surgically treated arteries. Early results were excellent: in
      group I, no patient died, no patient presented major or minor stroke. Only one
      patient had an immediate transient ischemic attack (TIA) which spontaneously
      recovered within 24 hours. All symptomatic patients examined the complete
      disappearance of clinical signs. There were no late deaths due to stroke and no
      late major or minor neurologic deficit occurred. All reconstructed ICAs were
      patent. In group II, three patients experienced a major stroke with hemiplegia
      due to ICA occlusion. Most of the symptomatic patients (37) of group II remained
      stable, while seven of them had worsening of symptoms and were referred for
      surgery. To conclude, all surgically treated patients had the complete relief of
      preoperative neurologic symptoms; none of the medically treated patients had an
      improvement. Although there was no statistically significant difference between
      the two groups with regard to stroke risk, three medically treated patients
      progressed to total occlusion. This suggests that kinking, coiling, tortuousity,
      and angulations of the ICA are not merely an anatomic curiosity but a potentially
      disabling, even fatal condition.

PMID- 9181767
TI  - The Dialine II graft: a new collagen-impregnated warp-knitted polyester arterial
      prosthesis.
AB  - The Dialine graft, a new prototype of knitted vascular prosthesis that uses a
      different brand of polyester fibers as an alternative to Dacron fibers, has been
      shown to offer excellent in vitro physical performance and in vivo healing.
      Although it still requires preclotting, the Dialine prosthesis was made
      impervious by impregnation of bovine type I collagen cross-linked with vapors of
      formalin. The purpose of the present investigation was to compare the in vitro
      physical characteristics of the Dialine II graft with those of the collagen
      impregnated Hemashield graft. In addition, we studied the healing performance as
      a thoracoabdominal bypass in dogs for prescheduled periods of implantation
      ranging from 4 hours to 6 months. In vitro, the bursting strength, resistance to
      dilatation, and suture retention strength properties of the Dialine II prosthesis
      were all shown to exceed those of the Hemashield control graft. In the first
      weeks after implantation, the Dialine II grafts induced a discrete inflammatory
      response, as shown by the constant leukocyte counts observed both before
      implantation and when the animals were killed, as well as by the histologic
      observation of a few inflammatory cells in contact with the collagen.
      Consequently, the Dialine II grafts showed a slow rate of bioresorption of cross
      linked collagen. At 1 month, a thin internal collagenous capsule was present at
      both anastomoses, laying over the original collagen coating. At 3 and 6 months,
      areas of thrombotic deposits and endothelialized areas were observed on the
      luminal surface. Because results of early clinical trials have been highly
      satisfactory, this prosthesis may be recommended for use without restriction as a
      medium- and large-diameter blood conduit.

PMID- 9181768
TI  - Accelerated endothelialization model for the study of Dacron graft healing.
AB  - Accelerated endothelialization was studied by creating a vascular tissue
      environment around porous Dacron grafts. Three study groups, each containing 10
      dogs, were divided equally into 2- and 4-week implant periods, with 8 mm x 6 cm
      knitted Dacron grafts implanted in the abdominal aorta. Grafts in group 1, the
      control group, were implanted conventionally. In group 2 each implanted graft was
      completely wrapped in a resected segment of the autogenous inferior vena cava,
      with its intima against the wall. In group 3 the adventitial side of the vein was
      wrapped against the wall. The vein wrap produced accelerated endothelialization
      as follows: endothelial-like cell coverage scores at 2 and 4 weeks were,
      respectively, 78% and 98% for group 2 and 80% and 95% for group 3, compared to
      only 14% and 50% for group 1 (p < 0.05). The neointima, which contained smooth
      muscle cells, was formed as early as 2 weeks in the vein-wrapped grafts. There
      were no differences in the speed of healing or in healing patterns according to
      whether the intimal or the adventitial side of the inferior vena cava was placed
      against the graft. Histologic findings did not support the hypothesis that
      accelerated flow surface endothelialization results in direct migration of
      endothelial cells from the intima of the vein wrap, and there was no clear
      correlation between the surface endothelial-like cell coverage and microostia. To
      gain further insight into why accelerated healing occurs in this model, earlier
      observations accompanied by molecular biology analysis are needed, and vein wrap
      studies provide a method of comparison for this work.

PMID- 9181770
TI  - POSSUM and APACHE II scores do not predict the outcome of ruptured infrarenal
      aortic aneurysms.
AB  - Forty consecutive patients were admitted alive to the operating theater with
      ruptured infrarenal aoritc aneurysms in a 3-year period and were assessed
      preoperatively with two scoring systems: the POSSUM (physiological and operative
      severity score for the enumeration of mortality) and the APACHE II (acute
      physiologic and chronic health evaluation). The aim of the study was to
      investigate the capacity of the two scores to predict the patients' outcome. The
      operative mortality of the series was 55% (22/40). The average POSSUM score was
      63.3 for survivors and 66.5 for the nonsurvivors (difference not statistically
      significant). APACHE II score averaged 11.3 in survivors and 14.5 in nonsurvivors
      (p = 0.02). APACHE II score 17 was the threshold value with the highest combined
      specificity and sensitivity; however, at this point the positive predictive value
      for a death was 92% and the negative predictive value was 63%. Interestingly, the
      only single factor in univariate analysis affecting mortality was the
      preoperative platelet count and is not taken into account in neither of the two
      scoring systems. POSSUM failed in predicting the outcome of ruptured infrarenal
      aortic aneurysms. APACHE II was a good predictor of outcome; however, its power
      to predict the outcome in any given individual patient was limited. As precise
      prediction is impossible, repair in every patient should not be denied.

PMID- 9181769
TI  - A multidisciplinary approach to the treatment of Paget-Schroetter syndrome.
AB  - To assess the results of thrombolytic therapy and surgical decompression of the
      thoracic outlet in the management of spontaneous axillary vein thrombosis (AVT),
      the records of 38 patients at New York University Medical Center (NYUMC) with AVT
      were reviewed. Excluded from this report were 20 patients who had AVT secondary
      to an underlying medical condition, a subclavian catheter, or a failed dialysis
      access graft. Of the 18 remaining patients with no underlying medical condition,
      all were found to have effort-related axillo-subclavian thrombosis, Paget
      Schroetter syndrome. Urokinase was used for thrombolysis in 17 of the 18
      patients, (94.4%) with complete lysis in 14 (82.4%). The remaining patient
      received anticoagulation only following a favorable response to an initial
      heparin infusion. Of the patients achieving complete thrombolysis, all but one
      received urokinase within 8 days of the onset of symptoms. Clot lysis revealed
      axillary vein compression secondary to a thoracic outlet syndrome in 11 patients,
      and these underwent staged transaxillary thoracic outlet decompression by first
      rib resection. All 17 patients have been followed for a mean of 21 months, and
      none receiving lytic therapy have reoccluded. Review of these data confirms
      earlier reports showing that with early diagnosis, thrombolysis and, if
      indicated, thoracic outlet decompression, patients with spontaneous AVT can
      expect excellent clinical results with a good long-term prognosis.

PMID- 9181771
TI  - Pulsed transthrombotic fibrinolysis: technique and results in the management of
      occluded lower limb bypass grafts.
AB  - Between March 1987 and March 1993 we used pulsed transthrombotic fibrinolysis to
      treat 58 symptomatic thrombotic occlusions of lower limb bypass grafts in 45
      patients. There were 17 suprainguinal grafts and 28 infrainguinal grafts.
      Treatment consisted of pulsed infusion of fibrinolytic agents into the thrombus
      followed by continuous infusion using an electric pump. Minor percutaneous or
      surgical procedures were often associated. The mean delay to treatment was 7
      days. The mean duration of treatment was 150 +/- 66 minutes. Immediate patency
      was achieved in 88% of cases with no significant difference between suprainguinal
      and infrainguinal grafts. The clinical success rate was 55%. Actuarial patency at
      1 year was 54% +/- 11% for suprainguinal grafts and 26% +/- 7% for infrainguinal
      grafts. The probability of patency was much lower in patients whose grafts had
      been implanted within 3 months before occlusion and in patients in whom an
      adjuvant procedure had not been performed. This study demonstrates that, in cases
      not requiring immediate surgery, pulsed transthrombotic fibrinolysis can achieve
      durable patency by treating both the bypass and distal arterial network. This
      technique allows identification of lesions causing thrombosis and adaptation of
      treatment specifically to these lesions.

PMID- 9181772
TI  - Superior patency of perforating antecubital vein arteriovenous fistulae for
      hemodialysis.
AB  - A comprehensive review of vascular access procedures at one institution over a 10
      year period was performed to assess primary hemodialysis (HD) access patency. A
      total of 427 operations were performed between January 1983 and January 1993.
      There were 147 Brescia-Cimino fistulae (B-C fistula), 111 perforating antecubital
      vein (PAV) fistulae, and 28 synthetic graft fistulae. There were 134 patients who
      were not considered candidates for arteriovenous fistula (AVF) formation and
      received only central venous HD access. Seven external fistulae in burn patients
      were deleted from the study. No patient in this study had undergone prior HD
      access. Primary failure was defined as fistula thrombosis, inadequate flow for
      hemodialysis, or a complication requiring ligation. Kaplan-Meyer life table
      analysis was used to determine primary fistula patency. The results were as
      follows: PAV fistulae had a primary patency rate of 80% at a median follow up of
      36 months (1-124 months); the B-C fistula was 66% at a median 27 months (1-120
      months), and the synthetic graft fistula was 64% at median 7 months (1-40
      months). The primary patency rate of the PAV fistula was significantly better
      than the B-C fistula (p = 0.0015) or the synthetic graft fistula (p = < 0.0001).
      In conclusion, the PAV fistula has an excellent patency rate and appears to be a
      viable option for AV access after a failed B-C fistula or when a B-C fistula is
      not technically feasible.

PMID- 9181773
TI  - Screening for patent foramen ovale and prevention of paradoxical embolus.
AB  - Paradoxic embolus is uncommon. Definite diagnosis requires demonstration of
      thrombus astride a patent foramen ovale (PFO) in a patient presenting cerebral or
      peripheral arterial embolism. With current echocardiography techniques, it is now
      possible to identify subjects with a PFO at risk for paradoxal embolism, however,
      the possibility of screening rekindles debate on prophylaxis and treatment. In
      the present report, we describe a case involving a woman who presented acute
      ischemia of the lower extremities with all the pathophysiologic features of
      paradoxical arterial embolism.

PMID- 9181774
TI  - Radiation-induced arterial disease of the lower limb.
AB  - We describe a case of radiation injury to the superficial femoral and upper
      popliteal arteries in a 39-year-old man treated 13 years earlier for an
      osteosarcoma of the right femur. Following two failed attempts at transluminal
      angioplasty, a saphenous vein femoropopliteal bypass graft was performed
      successfully. A comprehensive review of the literature on radiation-induced
      arterial injury to the limbs is presented with a discussion of the different
      management options. Percutaneous transluminal balloon angioplasty seems to have
      no place in the treatment of such lesions.

PMID- 9181775
TI  - Ehlers-Danlos syndrome type IV: a heterogeneous disease.
AB  - The Ehlers-Danlos syndrome is an inherited disorder of connective tissue,
      consisting of at least 10 different clinical subtypes. Type IV Ehlers-Danlos
      syndrome is an autosomal dominant condition characterized by the joint and dermal
      manifestations as in other forms of the syndrome but also by the proneness to
      spontaneous rupture of bowel and large arteries. The authors describe their
      experience with three patients presenting type IV Ehlers-Danlos syndrome: the
      first presented with several subsequent arterial ruptures, the second with
      multiple aneurysms, and the third with a dissection of the internal carotid
      artery. Clinical features, incidence, diagnosis, and treatment of the syndrome
      are discussed.

PMID- 9181776
TI  - Sarcoma arising from an abdominal aortic aneurysm.
AB  - A rare case of retroperitoneal sarcoma arising from an aneurysm sac is diagnosed
      in a patient following tube graft repair of the abdominal aortic aneurysm. The
      radiographic studies illustrate the characteristics of malignancy which are
      distinguishable from more common vascular complications. Malignancy should be
      considered in the differential diagnosis of retroperitoneal masses during
      radiographic follow-up of patients after aortic surgery. Sarcoma is optimally
      treated with complete excision, sometimes requiring concomitant vascular
      reconstruction. Radical en bloc resection was not attempted in this case due to
      extensive involvement of the aorta and inferior vena cava.

PMID- 9181777
TI  - Hans von Haberer: a forgotten pioneer in vascular surgery.
AB  - After carrying out the first free vein graft transplantation on an aneurysm of
      the axillary vein by Lexer in 1907, many attempts were made to reconstruct
      arterial injuries with direct vascular suture technique or vein graft transplants
      during the Balkan War (1912) and the First World War (1914-1918). Hans von
      Haberer gained wide experience in the reconstructive surgery of traumatic
      aneurysms at the Department of Surgery at the University of Innsbruck. During
      this period, he operated on a total of 201 vascular aneurysms, mainly using a
      direct circular vascular suture technique. In 1914, von Haberer described the
      first reconstruction of a carotid aneurysm. First experiences with vein bypasses
      were made, but not pursued in the following years.

PMID- 9181778
TI  - Gene therapy for vascular disease.
AB  - Atherosclerosis is a degenerative process characterized by endothelial cell
      dysfunction, inflammatory cell adhesion and infiltration, and the accumulation of
      cellular and matrix elements leading to the formation of fibrocellular plaques.
      In the end stages, advanced occlusive plaques limit blood flow and oxygen
      delivery resulting in the well-known ischemic syndromes of the coronary, skeletal
      muscle, mesenteric, and cerebrovascular circulation. Moreover, sudden critical
      ischemic events may be precipitated by plaque disturbance, rupture, hemorrhage,
      and/or thrombosis. Traditional pharmacologic approaches have been effective in
      reducing serum cholesterol and controlling thrombosis but, in the main, have had
      little impact on the treatment of advanced lesions. The purpose of this review is
      to examine the current status of gene therapy for vascular proliferation,
      aberrant endothelial function, thrombosis, peripheral ischemia, and modification
      of the blood/biomaterial interface.

PMID- 9181779
TI  - Use of endovascular grafts to treat nonaneurysmal arterial disease.

PMID- 9181780
TI  - Descending thoracic aorta to femoral artery bypass: surgical technique.

PMID- 9181781
TI  - The Role of Nitric Oxide in the Control of Cardiovascular System. Proceedings of
      a symposium at the 72nd annual meeting of Czech and Slovak Physiological
      Societies. Bratislava, February 6, 1996.

PMID- 9181782
TI  - [Dimeric and monomeric forms of dinitrosyl iron complexes with thiol-containing
      ligands: physico-chemical properties and vasodilator activity].
AB  - When studying the vasodilator activity of dinitrosyl iron complexes (DNIC) with
      thiol-containing ligands as NO donors, it should be taken into consideration that
      these complexes depending on the content of thiols in the environment can occur
      in either form that differ by their EPR, gamma-resonance and optical
      characteristics and also by their vasodilator effect on isolated blood vessels.
      The more stable diamagnetic form appears at the ratio Fe2+:RS(-)-1:2. It
      reversibly dissociates to the monomeric paramagnetic form [(RS-)2Fe+(NO+)2] on
      increasing the thiol content to the level 20 times and more exceeding the
      quantity of iron. It is suggested that stabilization of the dimeric form is
      provided by formation of RS(-)-NO+ bonds between monomeric components of the
      dimer. This process is favored by a corresponding orientation of the monomers
      relative to each other. A high stability of the DNIC dimeric form correlates with
      more prolonged vasodilator effect of this complex as an NO source. Replacement of
      cysteine by reduced glutathione in dimeric and monomeric forms of DNIC increases
      both stability of the complexes and the duration of their vasodilator effect.

PMID- 9181783
TI  - [Interaction of divalent cadmium ions with nucleotides and native DNA].
AB  - Complex formation of Cd2+ ions with 2'-deoxy-5'-phosphates of canonical bases and
      their riboanalogues in water solution is studied by the method of differential UV
      spectroscopy. It is stated that the atoms coordinating Cd2+ in complexes are N7
      of dGMP and GMP, dAMP and AMP, N1 of adenine derivatives, N3 of dCMP. No
      interaction with base heteroatoms of UMP and dTMP is found. O2' present in the
      structure of the sugar ring has a weak influence on the Cd2+ ion binding to
      purine nucleotides. It manifests itself strongly in the complexes with cytosine
      derivatives: cadmium does not interact with N3 of CMP and poly-C practically. In
      the last case O2 is a centre coordinating Cd2+ ions. The interaction with this
      atom induces the melting of polynucleotide helical parts. At the high cadmium
      concentration poly-C forms compact particles. The main centre binding Cd2+ ions
      in DNA is N7 of guanines. Noncooperative interaction with these centres results
      in the internal protonation of N3C of GC-pairs. This is not followed with the
      disordering of the DNA helical structure.

PMID- 9181784
TI  - [The role of ethanol during gamma-irradiation of water-salt DNA solutions].
AB  - In this work we had assumed to clarify the role of the water structure in the
      process of the radiation damage of DNA. It is known that the aliphatic alcohols
      stabilize the water structure until the critical concentration. In this
      connection we have analyzed the changes of the long- and short-distance
      interactions in the DNA irradiated in the water-ethanol solutions with various
      concentration of the ethanol and ions of metal. It was shown that as the water
      structure becomes more stable the conformational damages in the DNA are
      decreasing and finally at the some concentration of the alcohol in the irradiated
      solution the damages disappear. By the achieving of the alcohol concentration
      which lead to the destruction of the water structure the radiation results in the
      same changes of the considered parameters as in the case of the DNA irradiated in
      the water-salt solution with ethanol. The analyses of the experimental data allow
      us to conclude that the radiation destroys the structure of the water and thus
      helps the positive ions from the solution to come nearer to the DNA, to say, the
      radiation reduce intramolecular electrostatic interactions. This concept allows
      us to explain the observed changes of intrinsic viscosity and the difference in
      the polarizabilities of the DNA in the process of the radiation damage.

PMID- 9181785
TI  - [Effect of imidazen in combination with RNA on the structure of DNA from sarcoma
      45].

PMID- 9181786
TI  - [Redox properties of peptides potentially regulating animal hibernation].
AB  - Weak redox properties of peptides isolated from the brain of hibernating animals
      were determined in reactions with free radicals. The peptides Thr-Ser-Lys-Tyr-Arg
      (NKT) and Tyr-Arg diminished concentration of anion-radicals of dye excited by
      light, thus demonstrating electron-acceptor properties toward radicals. In
      contrast, the peptides Thr-Ser-Lys-Tyr (RZ-5) and Asp-Tyr acted as electron
      donors in the same radical reactions. The possible role of redox properties of
      these peptides in their regulation of Ca currents in excitable tissues is
      discussed.

PMID- 9181787
TI  - [The effect of synthetic polycation of the quarternary ammonium salts of
      polymetacryoil lupinin on the ionic permeability of erythrocyte membrane].
AB  - It is shown that synthetic polycation quarternary ammonium salt polymetacryloil
      lupinine (poly-MACL) effects on passive ion permeability of erythrocytes
      membranes. The amplitude of Cl-/OH- exchange decreased in the buffer with SDS
      polycation complex and simultaneously with pH elevation K+ exflux increased. On
      the contrary, in presence of heparin co-effect of poly-MACL and SDS vanished.
      Thus, synthetic polycation in the complex with long-chain anion (SDS) injure the
      membranes and effect depends on lipophilic-hydrophilic balance of polycation-SDS
      complex.

PMID- 9181788
TI  - [Formation of quasilinear domain structures in lipid membranes].
AB  - The process of domain lipid structure formation in phoshatidylcholine layer is
      studied in the context of phase separation theory for two-component mixtures.
      Computer simulation has shown that as the result of distinctions of structure of
      hydrocarbon chain-in all-trans and gauche states phase separation of different
      lipid conformers occurs and quasilinear domain structure is formed in the region
      of pretransition. The repeat distance of obtained domain structure is reasonable
      agreement with the experimental data of the ripple mode in phase P beta, of
      phoshatidylcholine bilayer. Possible role of the In-plane quasilinear lipid
      structure in biomembranes is discussed.

PMID- 9181790
TI  - [Antioxidant properties of UV-irradiated blood plasma as determined by the
      photochemiluminescence method].
AB  - UV-irradiation of human serum albumin, tryptophan, and histidine resulted in
      products formation showing antiradical activity, as detected by increased latent
      period in development of luminol photochemiluminescence. UV-irradiation of
      ascorbic acid decreased its antiradical activity. Under UV-illumination,
      antiradical activity of blood plasma decreased rapidly followed by a gradual
      increase of antiradical activity. Apparently, the former effect (decrease of
      antiradical activity) is a result of photolysis of natural blood antioxidants,
      while subsequent increase of antiradical activity is a consequence of the
      accumulation of plasma protein photolysis products.

PMID- 9181789
TI  - [Effect of Fe2+ ions on the hemolysis induced by products of psoralen photo
      oxidation].
AB  - The effects of Fe2+ ions on haemolysis induced by previously photooxidized
      psoralen (POP-haemolysis) were investigated. It was shown that POP-haemolysis was
      strongly activated by Fe2+ ions when ferrous ions were added to erythrocytes just
      after addition of POP. If POP was preincubated with Fe2+ before mixing with
      erythrocytes, then POP completely lost its ability to induce haemolysis. These
      data indicate the peroxidic nature of POP products responsible for haemolysis.

PMID- 9181791
TI  - [Death of cells from mouse peritoneal exudate induced by products of reaction of
      Fe2+ ions with previously photo-oxidized psoralen].
AB  - Toxic effect of previously photooxidized in water psoralen on survival of mouse
      peritoneal exudate cells was investigated. Cell survival was determined by trypan
      exclusion test. It was shown that photooxidized psoralen itself did not induce
      trypan-positive cells while decrease in cell survival was observed in the case of
      simultaneous addition of photooxidized psoralen and Fe2+ ions to cell suspension.
      To evaluate the quantity of psoralen photoproducts which react with Fe2+
      photooxidized psoralen Fe2+ mixtures were titrated by different cell
      concentrations. Then parameter c50 (cell concentration such that 50% trypan
      positive cells were observed) was determined. It was shown that c50 increased
      with the increase in preirradiation fluence of psoralen from 4.5 to 45 kJ/m2. But
      further increase in preirradiation fluence resulted in decrease of c50. The
      photodestruction of psoralen photoproducts which react with Fe2+ ions was
      proposed. Simultaneous addition of photooxidized psoralen, Fe2+ ions and
      antioxidant butylated hydroxytoluene significantly increased cell survival. That
      indicated free radical nature of reaction products of photooxidized psoralen with
      Fe2+ ions.

PMID- 9181792
TI  - [Dynamics of electrodermal activity during changes in the hydration of the
      epidermis: theoretical model].
AB  - The presented theoretical model explains three ways of epidermal hydration
      changes. These ways are; water movement from both dermal layer and sweat gland
      ducts to the epidermis, and then, from the epidermis to the air. Epidermal
      hydration changes influenced electrodermal activity. It was revealed, that
      epidermal hydration changes impact both amplitudes and latencies of the
      electrodermal activity.

PMID- 9181793
TI  - [Mathematical model of development of long-term synaptic plasticity].
AB  - Proposed mathematical model is described the long-term synaptic plasticity
      creation as the postsynaptic process based on the number of membrane receptor
      increase. The transmitter as the "marker" of the receptor type synthesis and the
      protein kinase as the activator of this protein synthesis are proposed.

PMID- 9181794
TI  - [Effect of inhibitory-inhibitory connections and the form of postsynaptic
      potentials on the formation of rhythmic processes in the cerebral cortex:
      analysis of the approximate equation of the electroencephalogram].
AB  - The integral equation, describing the electroencephalogram and taking into
      account the steepness of PSP fronts, delays of action potential spread, and
      neural Inhibito-inhibitory connections, is derived and analysed. The damping
      decrements and frequencies of the equation solutions in the continuum of
      parameters, associated with total numbers excitatory and inhibitory neurons in
      the cerebral cortex, density of synapses, and average level of excitation of
      cortical neurons are considered. The steepness of PSP fronts does not
      qualitatively change the solution's structure with the influences of EPSP and
      IPSP fronts being opposite. The inhibito-inhibitory connections expand the damped
      solutions regions. The delays of action potential spread between excitatory
      neurons enlarge the damped solutions region, and the delays in ones between
      inhibitory and excitatory neurons decrease it, especially for higher frequencies.

PMID- 9181795
TI  - [Potential mechanism of therapeutic effect of magnetic effect of magnetic field
      and photic stimulation on the nerve fibers in the visual tract].
AB  - Constant and alternating external magnetic fields induce a sedative effect due to
      Lorentz forces and also stimulate indirectly metabolic processes. With the
      properly chosen polarity of the inductor and its position relative to nerve
      fibers, and with asymmetric and inhomogeneous electrical conductivity in the
      vicinity of excited fibers, which can be enhanced by pattern light stimulation,
      magnetic fields produced by asymmetric impulses with one steep front (fore and
      back) can further enhance excitability and conductivity.

PMID- 9181796
TI  - [Roentgenographic study of the duodenal juice components in the dog].
AB  - It is shown that X-ray pattern rich in reflections that we have received earlier
      from concentrated canine duodenal juice is the sum of the patterns arising from
      both mucin macromolecules and from unknown component of the juice. The functional
      role of the duodenal juice regularity observed is discussed.

PMID- 9181797
TI  - [Prospects for intensification of real motor activity during bonding of humans
      with virtual computer spaces].
AB  - In this article you can familiarize yourself with big experience of using
      computer signals that are necessary in order to operate by them. These signals
      arise on the basis of values transformation and afforts directions that are
      applied to powerful connections of different training devices. Similar
      opportunities of interaction with computer games programmes were tested on the
      basis of using a plant to control the dozing projection displacements of masses
      common centre on area of support.

PMID- 9181798
TI  - [Interpretation of the resonance Raman spectrum of cytochrome P-450].
AB  - Normal coordinate analysis has been carried out for the Fe(III) protoporphyrin IX
      dimethyl ester molecule and its vinyl deuterated analogs. All atoms of
      substituents were included explicitly in the calculations. On the basis of the
      calculation results the assignment of the resonance Raman active modes of
      cytochrome P-450 is given. Attention is mainly devoted to the assignment of vinyl
      and methyl propionate ester modes. It is shown that methyl propionate ester
      coordinates take part to a certain extent in the number of modes with frequencies
      below 1300 cm-1. The frequencies have been found which depend on the angle
      between the vinyl and macrocycle planes. In passing from perpendicular to in
      plane conformation the theoretical frequencies of the delta (Cb C alpha C beta
      and delta (CCb C alpha) modes shift down by 70 and 220 cm-1 and the value of the
      last one is only about 110 cm-1.

PMID- 9181799
TI  - [Cu(II) complexes with biomacromolecules. The use of Cu(II) ions as a structural
      spin label].
AB  - Complexes of Cu(II) ions with globular proteins (human serum albumin, bovine
      serum albumin, egg albumin, lisozim and DNA) have been studied using the ESR
      method. It was shown that Cu(II) ions may be use as structural "spin-label" to
      study conformational dynamics of macromolecules, including structural transition
      in biopolymers.

PMID- 9181800
TI  - [Comparison of dynamic properties of various globular proteins and polyglutamic
      acid in alpha-helical and coil states. Rayleigh scattering of Mossbauer radiation
      data].
AB  - Classical model system: Poly-L-glutamic acid (Poly-Glu) was investigated in a
      disordered coil state (at pH-7.0) and in helix state (at pH 2.0) by Rayleigh
      scattering of Moessbauer radiation technique. Consider that the coil state of
      poly-Glu models unfolded (random coil) state and alpha-helix state models the
      fluctuating secondary structure (during consequent folding of protein)
      comparative analysis of dynamical properties of poly-Glu in different states with
      dynamical properties of different proteins in native state (alpha-helical
      myoglobin and HSA, partially beta-sheet lysozyme) and in intermediate (molten
      globule) state (alpha-lactalbumin) was performed. This comparison bring some
      surprising results: native alpha-helical proteins behave itself close to random
      coil, native partially beta-sheet protein behaves close to fluctuating secondary
      structure (alpha-helix) and the dynamic behaviour of molten globule state
      (partially beta-sheet alpha-lactalbumin) is not different from those behaviour of
      lysozyme and much more rigid than native alpha-helical proteins. As a result one
      cannot exclude the possibility that folding process and dynamical properties at
      different steps of the folding are very different for alpha-helical and beta
      sheet proteins.

PMID- 9181801
TI  - [Molecular dynamics of oligopeptides. 1. The use of long trajectory and high
      temperature data for determination of statistical weight of conformational
      substates].
AB  - The method of molecular dynamics investigations of the particularities of
      macromolecule physical-chemical properties is discussed. The results, obtained
      from the calculations of modified dipeptides in different regimes (different
      temperatures, length of trajectories and ways of thermostat simulation) are
      compared. The optimal conditions for this peptides calculations are determined:
      collisional dynamics regime, trajectories not less than 5000 ps, temperature
      about 1000 K. In this case the figurative point is able to scan the molecule
      configuration space and the statistically reliable results could be obtained.

PMID- 9181802
TI  - [Effect of the length of molecular chain on the formation of triple-helical
      collagen-like complex in solutions. The role of water in the formation of triple
      helix].
AB  - Effect of molecular chain length on the formation of the collagen-like triple
      helix in synthetic oligotripeptides Z-(Gly-Pro-Pro)n-OMe (n-1,2,3,...,8) in
      solutions has been studied, using IR- and CD-spectroscopy methods. The helix
      formation under different conditions is investigated: in the presence of a
      relatively inert solvent (chloroform), in the presence of a hydrogen bond
      acceptor (dioxan), in the presence of a hydrogen bond acceptor and donor as well
      (ethanol). Special attention is paid to the role of water in the formation of a
      stable triple-helical structure. Successive stages in the formation of a stable
      triple-helical structure in solutions during elongation of the peptide chain is
      revealed, which may be correlated with the helix nucleation process. A minimum
      peptide length, when peptide chains are still able to associate in the collagen
      like triple-helical complex, involves three triplets for oligomers in chloroform
      solution, four triplets for oligomers in dioxan and ethanol solutions, six
      triplets for oligomers in aqueous solution. The main features of the completed
      triple-helical structure in water are found already in the oligotripeptide with n
      8, where the formation one full turn of the superhelix is finished.

PMID- 9181803
TI  - [Thermal properties of collagen-water system. 1. Increments of heat capacity
      during denaturation and glass transition].
AB  - The absolute values of heat capacity of the collagen-water systems with different
      relative content of the components in both native and denatured state were
      studied by the method of differential scanning calorimetry in a wide temperature
      range (-40 +/- 140 degrees C) which includes the region of the denaturation phase
      transition as well as the region of the relaxation glass transition. From the
      experimental data the values of denaturation increment delta Cpnd-0.42 +/- 0.04
      J/(g.K) at the collagen content 10-50% and the values of glass transition
      increment delta Cpg-0.54 +/- 0.12 J/(g.K) for moist denatured protein were
      calculated. Different processes influencing the increment values are analysed.
      The nonequilbrium character of the glass-like state of moist proteins was clearly
      demonstrated in the study of glass transition.

PMID- 9181804
TI  - [Calorimetric study of thermodynamic parameters of collagen denaturation in
      diluted solutions at different rates of scanning].

PMID- 9181805
TI  - [Denaturation increment of heat capacity in diluted aqueous solutions of
      collagen].
AB  - The experimental values of the denaturation increment of collagen heat capacity
      in diluted aqueous solutions, obtained at different scanning rates, are
      presented. It is shown that the dependences of the "equilibrium" enthalpy and
      entropy of collagen denaturation on denaturation-induced variation in heat
      capacity do not obey the empiric law of the linear correlation of the
      thermodynamic parameters of denaturation at 25 degrees C for globular proteins,
      indicating that the stabilization of the triple collagen helix proceeds by a
      special mechanism with the participation of water molecules.

PMID- 9181806
TI  - [Statistical characteristics of splicing sites in vertebrates and invertebrates].
AB  - Human, rodent, Drosophila and nematode Caernorabditis elegans splicing sites have
      been analyzed. The estimated strength of the nematode donor sites positively
      correlates with the length of the adjacent exon. The Drosophila acceptor site
      strength negatively correlates with the length of the adjacent intron. GC-content
      of the polypyrimidine tract of the human and rodent acceptor sites and the G/A
      choice in the third intron position of the human donor sites correlates with the
      local GC-content of the site neighbourhood.

PMID- 9181807
TI  - [The effect of ligands undergoing temperature conformational transitions on the
      stability of DNA double helix].
AB  - The influence of ligands, which undergo conformational transition, on DNA
      molecular melting is considered theoretically. Equations for computation of
      melting curves of DNA included in such complexes are obtained, which are used for
      studies of DNA double helix stability and of the binding to helical and coil
      regions influence on ligand conformational transitions. Calculated melting curves
      and experimental data for DNA-RNAase complex are compared.

PMID- 9181808
TI  - [Effect of low temperatures on molecular parameters of DNA].
AB  - Cryoconservation effects on macromolecular parameters of DNA from reproductive
      cells of fishes are studied as well as cryodamages of DNA in solutions under
      various freezing conditions, by the viscometry method. A dependence of the low
      temperature action on DNA concentration in solution and on the action duration is
      determined. It is stated as well that the nitrogen temperature action on the
      biopolymer solution results in the formation of both double- and single-stranded
      breaks. The cryoprotector (ethylenglycol 12%) added into the solution frozen
      prevents from the formation of double-stranded breaks and decreases the number of
      single-stranded ones. The long-term (0.5 year) keeping of the biopolymer solution
      at -196 degrees C both under the cryoprotector (20% 1.2-propanediol) protection
      and without the cryoprotector induces the significant number of single-stranded
      breaks. Mechanisms of cryodamages of DNA macromolecules in cells and under the
      nitrogen temperature action are discussed.

PMID- 9181809
TI  - [Tuberculosis in the elderly patient].

PMID- 9181810
TI  - [The clinical characteristics of pulmonary tuberculosis in the elderly].
AB  - Pulmonary tuberculosis remains as a significant clinical problem in the elderly.
      To describe age-related differences in disease manifestations, a comparison was
      made taking in consideration predisposing factors, clinical features,
      radiographic findings and diagnostic approaches in cases of pulmonary
      tuberculosis between two groups: equal o higher of 60 years and lower of 60
      years. Elderly patients had a higher number of antecedents of previous
      tuberculosis and underlying diseases than younger patients. At admission,
      symptoms like fever and hemoptysis were more frequent in the younger group.
      Radiographic findings revealed that upper lung infiltrates were still common in
      both groups, and that elderly patients presented less pleural effusions and
      cavitary lesions than younger patients. Since there were differences in the
      clinical presentations of pulmonary tuberculosis in the elderly group, a high
      index of suspicion for the disease should be maintained.

PMID- 9181811
TI  - [Tuberculosis epidemiology in the Cervo (Lugo) health area].
AB  - From 1994 to 1995, 80 cases which belonged to 78 patients were diagnosed. The
      rate was 56.6 cases/100,000 inhabitants/year in 1994 and 51.2 in 1995. The ratio
      male/female was 2:1 for the two years. Diagnose in hospital was 73% and in health
      centre 27%. Acid-fast stain and/or positive culture of M. Tuberculosis (MT) and
      another mycobacteria were obtained in 82.5% cases. The MT resistances were about
      3.6. It was usually placed in lungs in 69.2%. The 5.1% patients were positive for
      HIV. Only one patient died (1.8%) who suffered from a miliary form. The favorite
      administered treatment (78.2%) was six months with three drugs. The adenosine
      deaminase (ADA) was discriminate for 80% of pleuritis. The average stay was 17.6
      days. Important differences in each town councils rates.

PMID- 9181812
TI  - [The use of cefotaxime on patients admitted to the internal medicine service of a
      general hospital. An analysis from the viewpoint of health economics].
AB  - Cefotaxime is a widely employed antibiotic in hospital practice, leading to an
      important economical cost. We analyse the adequacy of the indications of
      cefotaxime in our Internal Medicine Unit along a two month period. The records of
      the 54 patients treated with cefotaxime along a two month period were
      retrospectively reviewed to establish the adequacy of the prescriptions by
      checking them with a list of indications based on widely used bibliographical
      sources. Cefotaxime prescription was considered inadequate because of its
      inefficiency in 15 out of the 54 patients studied (28%). They were all patients
      admitted because of bronchitic relapses of chronic obstructive lung disease
      ("COLD") without radiological evidence of pneumonic consolidation. We calculate
      that using a more efficient antibiotic alternative could lead to a decrease of a
      3.6 to 7.53% in the total pharmaceutical expenses of our unit along the study
      period. We conclude that the unnecessary routine use of cefotaxime may lead to an
      avoidable important increase in sanitary costs.

PMID- 9181813
TI  - [The influence of empty-bed days on the median hospital stay in internal
      medicine].
AB  - BACKGROUND: To evaluate the epidemiology of delays in patients hospitalized in a
      department of internal medicine in a hospital of third level (high technology,
      end-stem of Spanish health system), its influences in hospital length of stay and
      the leading reasons which we named Gap Days. PATIENTS AND METHODS: We studied all
      patients admitted through emergency ward for internal medicine during Oct 93-June
      94. Gap Day was defined as the day passed as inpatient in which no intravenous
      route, isolation, artificial feeding, fever, impairing of clinic steady-state
      were needed or waited and any diagnostic tools were used. We counted Gap Day from
      the second day and from de third day for histopathology that we ordered the
      explorations. In a nonselected group days of delay to arrive written data were
      measured while the results were known for personal request. RESULTS: 144 patients
      had a mean length of stay of 9.52 (SD 5.41) days. Gap Days occurred in 97 (67%)
      patients (Mean 3.85 SD 2.80) with a mean length of stay 10.71 SD 5.09 days, while
      patients without Gap Days had a mean length of stay of 7.14 SD 5.29 days (p <
      0.001). Patients with higher Gap Days were those with symptoms related to
      hematological system (p = 0.002), nephrourological system (p = 0.011) and a
      hematological diagnostic (p = 0.003) on admission. On discharge patients with
      hematological diagnostic had also higher Gap Days (p = 0.017). They had higher
      Gap Days also patients with two symptoms or more on admission (3.63 SD 2.96, p =
      0.016), patients who lived alone (5.33 SD 3.42, p = 0.050) and patients with no
      concordance between diagnostic on admission and discharge (4.06 SD 3.41, p <
      0.01). In 37 patients written data arrived 2.14 SD 1.06 days later after to know
      the results for personal request. CONCLUSION: Gap Days are an important factor to
      prolong the length of stay in internal medicine. They are influenced by number of
      symptoms on admission, concordance between diagnostics on admission and
      discharge, hematological diagnostics and some social and functioning hospital
      factors.

PMID- 9181814
TI  - [A metastatic muscle mass as the first manifestation of renal-cell cancer. A case
      report and review of the literature].
AB  - Although metastasis is relatively frequent in renal cell carcinoma (affecting
      mainly the lungs, lymphatic glands and bones), location of metastasis in muscles
      is extremely rare as in other oncological processes. The literature only offers
      isolated cases of renal cell carcinoma with metastasis in muscles, and no
      preferred muscular site is found in these cases nor is there any clear intrinsic
      relation to prognosis, having been described both at the onset an upon relapse of
      the oncological process. The intimate mechanism behind this infrequent metastatic
      site is unknown even today but it presents a series of specific and peculiar
      factors such as vascular flow, metabolism and oxygen tissue pressure which can
      negatively condition this process. We present the case of a 60-year-old patient
      who began with a mass in the triceps muscle. A biopsy confirmed its metastatic
      nature and indicated an asymptomatic renal cell carcinoma. Further complementary
      examinations showed metastasis in other muscle groups.

PMID- 9181815
TI  - [Eosinophilic gastroenteritis, apropos a new case].
AB  - Eosinophilic gastroenteritis is an uncommon disorder, characterised by
      eosinophilic infiltration of gut wall, with variable clinical features, depending
      affected layer of the wall and digestive area, but usually consisting in
      abdominal pain, diarrhoea, and vomiting. Etiopathogenesis is unknown, with a
      frequent allergic condition and good response to corticosteroids therapy.
      Although the existence of eosinophilic gastroenteritis may be suggested by
      abdominal manifestations, an allergic history with laboratory date and ESR
      normal, only the antral or intestinal biopsy might to confirm the diagnostic. We
      report a case of a patient with eosinophilic gastroenteritis and history of
      bronchial asthma, without evidence of intestinal parasitosis, and a spectacular
      response to corticosteroids therapy.

PMID- 9181816
TI  - [An adrenal carcinoma producing androgens, estrogens and cortisol].
AB  - Carcinoma of the adrenal cortex is a fairly rare entity, usually with a somber
      prognosis. The efficacy of treatment depends on early prognosis. We are reporting
      here a case of carcinoma of the adrenal cortex producing androgens, estrogens and
      cortisol, in which diagnosis was not achieved until two years after the onset of
      symptoms. Morphologic studies by CT showed local extension and metastases. After
      mass-reduction surgery, the patient died due to respiratory failure. This case
      remarks the importance of early diagnosis in this syndrome.

PMID- 9181817
TI  - [Heterotopia in a 45-year-old man].
AB  - Heterotopia is a neuronal migration disturbance, which clinical picture is
      characterized by mental retardation and seizures in childhood. We present a new
      case, a 45 year old man without any previous clinical manifestation, and two
      years follow-up with neuroimagen and electroencephalographic studies.

PMID- 9181818
TI  - [Anticentromere antibodies and lung disease without skin involvement].
AB  - Anticentromere antibodies are closely related to systemic sclerosis and basically
      to limited cutaneous form. Two patients with different forms of lung disease,
      positive anticentromere antibodies and absence of the characteristic skin
      involvement of the systemic sclerosis are presented.

PMID- 9181819
TI  - [Neutropenia in HIV infection].
AB  - The infection by human immunodeficiency virus (HIV) are commonly associated with
      haematologic abnormalities (anemia, leucopenia and thrombocytopenia). We review
      the neutropenia. In patients infected with HIV neutropenia is seen in the 8-50%
      of them, and also have abnormalities in the neutrophil function. ETIOLOGY: Direct
      injury of HIV on de bone marrow, anti-neutrophil antibodies, drugs, opportunistic
      infections of bone marrow, vitamin B12 and folate deficiency, radiations therapy,
      and hemophagocytic syndrome. CONSEQUENCES: These patients have a increased risk
      of infections, since the neutrophils play an important role in the defense
      against bacterial and certain fungal infections. TREATMENT: It must to treat the
      causes. When it is not possible, Colony-Stimulating Factor can be use to
      stimulate the bone marrow granulopoiesis.

PMID- 9181820
TI  - [Pulmonary hemorrhage after thrombolysis in acute myocardial infarct].

PMID- 9181821
TI  - [Isolated general malaise of unknown origin. A new syndrome].

PMID- 9181822
TI  - [The SAPHO syndrome and ulcerative colitis].

PMID- 9181823
TI  - [Fat necrosis and pleural effusion, an unusual presentation of pancreatic
      pseudocyst].

PMID- 9181824
TI  - [The Stevens-Johnson syndrome and Lyme disease].

PMID- 9181825
TI  - [A new case of myxedematous coma with a fatal evolution].

PMID- 9181826
TI  - [A delay in the care for HIV patients in an area with a low rate of AIDS].

PMID- 9181827
TI  - [How relevant are calculations of mean intracompartmental pressure in functional
      compartment syndrome?].
AB  - The intracompartmental pressure in the anterior tibial compartment was documented
      under standardized conditions in 29 patients walking at a speed of 4.5 km/h, as
      well as heel-and-toe running at a speed of 8 km/h. All pressure curves were
      integrated and the resulting mean pressure was compared with the arithmetic mean
      pressure indicated in the literature. During walking, the difference between
      calculated and integrated pressures was between 80 and 140%. In the case of heel
      and-toe running, the difference was between 80 and 165%. On the basis of these
      results, the calculation of the mean intracompartmental pressure recommended in
      the literature does not appear to be of any clinical relevance.

PMID- 9181828
TI  - [Electromyograms in erectile dysfunction and computer-assisted interpretation].
AB  - The electromyogram of the corpora cavernosa (CC-EMG) provides information on the
      autonomic innervation and/or smooth musculature. The interpretation of the CC
      EMG, usually by evaluating signal patterns of higher activity, is time-consuming.
      To improve this situation, a computer-aided diagnosis employing a Microsoft
      Windows user interface was developed. The computer-aided interpretation is based
      on digital measurement data obtained using a 170.6 Hz sampling frequency and
      quantization of 10 V/12 bits of the signal. The first task of the program is to
      extract signal patterns of higher activity from stored data. To describe these
      patterns in mathematical terms, the features "relative time position", "relative
      reproducibility", "portion of normal phases", and "portion of whip phases" are
      calculated. Characteristic signal forms (normal and whip phases) are identified
      by means of syntactic pattern recognition. Using fuzzy logic, the features are
      used to effect pattern evaluation. To summarize the evaluated patterns, the
      variable "global normality" has been established, and linked to the "global
      synchronicity" at a second fuzzy logic level, to produce the final diagnosis.
      Finally, 30 records were evaluated independently by a team of experts and by the
      computer program. In relation to four established diagnostic classes, a
      correspondence of 70% was found. Furthermore, the accuracy achieved in each of
      the individual classes was better than 50%. Discrimination between normal and
      abnormal evaluation, which is of particular interest, reached 80%.

PMID- 9181829
TI  - [Computer-based assessment of visual acuity--technical realization].
AB  - Testing of visual acuity for distant vision can be computerized by using monitor
      screens to present optotypes. Because of the limited spatial resolution of
      conventional monitors, measurement of visual acuity for near vision is not
      possible. This paper describes a new computer-aided method for the measurement of
      both near and distant visual acuity. Our approach to the assessment of visual
      acuity for near vision is based on a recently developed liquid crystal display (a
      screen, LCD) measuring 10.5 mm x 15 mm. The LCD permits the presentation of
      optotypes for the measurement of visual acuity between 0.063 and 1.25 at a
      viewing distance of 40 cm (near/distant). The presentation of optotypes for the
      assessment of the acuity of distant vision uses a standard 17" monitor that
      permits visual acuity figures of between 0.032 and 1.6 to be assessed.

PMID- 9181831
TI  - Anorexia during acute and chronic disease: relevance of neurotransmitter-peptide
      cytokine interactions.

PMID- 9181830
TI  - [A new method of ex vivo whole blood perfusion of isolated mammalian organs,
      exemplified by the kidney of swine].
AB  - A new method for the ex vivo perfusion of organs from large mammals is described.
      Gas exchange and dialysis are carried out simultaneously with a low-flux
      polysulfon dialysis module. The dialysate (e.g. Tyrode solution) is aerated with
      a mixture of oxygen and carbon dioxide to ensure gas exchange with the blood.
      Dialysis is carried out in a closed thermostatically controlled system.
      Monitoring of ultrafiltration is maintained by continuously weighing the blood
      reservoir and adjusting an afferent and efferent blood pump. Initial results
      obtained with isolated pig kidneys demonstrate the suitability of the new method
      for use as a model for the replacement of animal experiments. Theoretically,
      clinical application in the area of in vivo regional organ perfusion may also be
      possible.

PMID- 9181832
TI  - ["From tradition into the future"].

PMID- 9181833
TI  - [Staphylococcus-associated blepharokeratoconjunctivitis. Clinical findings,
      pathogenesis and therapy].
AB  - BACKGROUND: Staphylococci represent an important source of external infections of
      the eye. In addition to acute staphylococcal conjunctivitis a spectrum of
      subacute or chronic disease may be found. According to Valenton und Okumoto, with
      this staphylococci-associated blepharo-kerato-conjunctivitis in culture-positive
      cases S. aureus is found in 31% and S. epidermidis in 69% of smears.
      Microbiallergic and toxic mechanisms are the underlying etiology. PATIENTS: We
      report on a series of 38 patients with "red eye" that were seen between 1992 and
      1994 in the external disease clinic at the Department of Ophthalmology,
      University of Heidelberg. RESULTS: There were 17 female and 21 male patients. The
      mean age was 53 +/- 20 years. The patient's complaints included recurrent red
      eyes with discomfort and pain. Clinically, a squamous blepharitis (63%) and
      conjunctivitis (87%) were present. Upon biomicroscopic evaluation, a corneal
      involvement could be found in 80% of cases. In 66% of cases conjunctival swabs
      were positive for staphylococci. DISCUSSION: The blepharitis may be squamous or
      ulcerative. The underlying cause is a dermal irritation by staphylococcal toxins.
      As early as 1937, Thygeson and Allan postulated a toxin-induced skin irritation
      by a "dermonecrotic factor." In chronic cases a papillary conjunctivitis caused
      by a toxin reaction can be observed. Histologically, no lymph follicles or
      eosinophils are present. Several types of keratitis and corneal involvement are
      found. An epithelial keratitis is caused by toxic mechanisms. Marginal
      infiltrates and ulcers indicate an antigen-antibody reaction. Phlyctenulae
      indicate a delayed immune reaction (Gell and Coombs type IV). Complications
      include vascular pannus, corneal scarring, and rarely corneal melting and ulcers.
      Therapy depends on the severity of the inflammation and the underlying
      pathomechanism. This includes reduction of toxin-producing organisms by hygiene
      of the lid margins and application of topical disinfectants and antibiotics. With
      immunological phenomena topical steroids are required.

PMID- 9181834
TI  - [Blepharitis. Demodex folliculorum, associated pathogen spectrum and specific
      therapy].
AB  - Demodex folliculorum has been demonstrated with an elevated frequency in patients
      with blepharitis, and is thought to cause therapy-resistant blepharitis. This
      paper presents the germ spectrum of patients with blepharitis and demodex and
      discusses the efficiency of a specific therapy. METHODS: In all, 3152 cilia from
      139 patients with blepharitis (38% blepharitis, 44% blepharoconjunctivitis,
      others) and 108 persons with quiet eyes were examined for demodex. Smears n =
      125, from the conjunctive of symptomatic patients were investigated for bacteria,
      3 weeks of therapy with mercury ointment, 2%: Lindan, cortisone (prednisolone,
      dexamethasone, hydrocortisone, fluorometholone) or antibiotics after antibiogram
      (gentamicin, kanamicin, neomicin, erythromicin, ofloxacin, polymyxin-B, colistin)
      followed in all Demodex-positive blepharitis patients (n = 41). RESULTS: Demodex
      was found in 52% (62/139) of patients with chronic blepharitis, as against 20%
      (3/15) of those with acute blepharitis (statistically significant difference, chi
      2-test, alpha = 2.5%) and in 29% of quiet eyes (statistically significantly less,
      alpha = 2.5%, chi 2-test). Gram-positive cocci were isolated from 79% of 57
      Demodex-positive patients with blepharitis and 72% of 68 Demodex-negative
      patients anaerobes in 39% and 37%, gram-negative rods in 11% and 3%
      (statistically significant difference for gram-negative rods, alpha = 5%, chi 2
      test). Of the patients with Demodex, 25% apparently had no more parasites after
      mercury ointment, 2% (n = 8) and lindan (n = 5) and 15% after cortisone and
      antibiotics (n = 13). (The best and statistically very significant results (alpha
      = 1%) were those obtained with mercury ointment, 2%, and lindan: t-test for
      connected spot checks). CONCLUSIONS: Gram-positive and gram-negative bacteria
      grew more often in patients with Demodex. Demodex seems to be a mediator of
      chronic blepharitis; we recommend that mites be sought in cilia of chronic
      blepharitis patients. Mercury ointment, 2% and lindan proved efficient for
      specific therapy, the main problem being the laborious application and toxicity.

PMID- 9181835
TI  - [Alpha/beta and gamma/delta T-cell receptors--analysis of conjunctival tissue of
      patients with ocular pemphigoid].
AB  - BACKGROUND: In the conjunctiva of asymptomatic persons and patients with ocular
      cicatricial pemphigoid the existence and distribution of alpha/beta- and
      gamma/delta-T cell receptor (TCR)-positive cells has not previously been
      investigated. PATIENTS AND METHODS: Biopsy specimens from 20 patients with
      clinically diagnosed ocular cicatricial pemphigoid (OCP) were compared with 20
      specimens from asymptomatic persons. Additionally, 3 specimens from patients with
      OCP treated with cytotoxic drugs and 8 specimens from patients who had undergone
      mucosal transplantation were studied. Antigen retrieval was done in
      deparaffinized specimens for immunohistochemical identification of alpha/beta-
      and gamma/delta-TCR-positive cells by monoclonal antibodies and an appropriate
      detection system. All steps were performed in triplicate, and negative control
      sera were applied. RESULTS: alpha/beta-TCR-positive cells were observed in the
      conjunctival epithelium and stroma of all the asymptomatic persons and in all
      patients with OCP. gamma/delta-TCR-positive cells were found in 4 out of 20
      patients with OCP in epithelial sites, but not in asymptomatic persons. Patients
      with OCP who had received cytotoxic treatment exhibited neither alpha/beta- nor
      gamma/delta-TCR-positive cells. Staining sites of alpha/beta-TCR-positive cells
      changed from membrane-bound to nuclear in patients who had undergone mucosal
      transplantation, and were cytoplasmic rather than membrane-bound in gamma/delta
      TCR positive cells. CONCLUSIONS: This study presents preliminary evidence for the
      existence of distinct T-cell subsets in the conjunctiva of healthy persons and of
      patients with OCP. Further functional studies in fresh tissue material may
      provide better insights into the role of defined T-cell subsets in the
      immunopathogenesis of autoimmune diseases of the outer eye such as OCP.

PMID- 9181836
TI  - [New clinical and epidemiologic aspects of episcleritis and scleritis].
AB  - Numerous systemic diseases can cause scleritis or episcleritis. Frequently,
      symptoms and complications compromising vision can only be managed with systemic
      immunosuppressants. There are no clear guidelines on the indications for systemic
      immunosuppressants in patients with episcleritis and scleritis. PATIENTS AND
      METHODS: The aim of the present retrospective study was to investigate how many
      patients with episcleritis or scleritis have an associated systemic disease and
      at what stage it is diagnosed. Secondly, the proportion of patients who present
      with episcleritis or scleritis in the first instance and then change into the
      other category during the course of the disease was analyzed. Finally, we checked
      whether the presence of an associated systemic disease indicates the necessity to
      treat the patient with nonsteroidal systemic immunosuppressive drugs. RESULTS:
      Sixty-eight patients with inflammatory scleral diseases were treated at the
      University Eye Clinic between 1991 and 1995. In 13 patients an associated
      systemic disease was diagnosed before the appearance of ocular symptoms, and in 8
      patients such an illness was diagnosed at a later stage. In 2 cases (3%) the
      ocular disease category changed during the course of the disease. Neither in the
      episcleritis nor in the scleritis population was a statistically significant
      correlation established between the diagnosis of an associated systemic disease
      and the necessity to treat the patient with nonsteroidal systemic
      immunosuppressive drugs. CONCLUSION: The small number of patients who changed the
      ocular disease category may indicate that episcleritis and scleritis are two
      independent entities, which might even be caused by different mechanisms. The
      indications for the management of episcleritis and scleritis with
      immunosuppressive drugs should not only depend on the diagnosis of an associated
      systemic disease, but also and mainly on the severity of the ocular
      manifestation.

PMID- 9181837
TI  - [Intraocular involvement of Chagas disease (American trypanosomiasis). Studies in
      Paraguay/South America].
AB  - BACKGROUND: In Central and South America, Chagas' disease is of great
      epidemiologic importance. The epidemiologic agent is represented by Trypanosoma
      cruzi, a monocellular parasite, instrumental in human infection is the presence
      of vectors, which are various species of hematophagous bugs. The eye is one of
      the most important entrance sites of the parasite, and relatively little
      information about the relationship between Chagas' disease and eye complications
      is available. PATIENTS AND METHODS: We examined 79 chagasic patients in order to
      detect changes in the retina. As a control group, we examined 48 patients with
      negative serology within the same age range and from the same regions. For every
      patient we completed a routine ophthalmologic examination, with inspection of the
      retina using direct and indirect ophthalmoscopy. RESULTS: In most of the chagasic
      patients, the ocular fundus was unobtrusive; in only 6 out of 79 cases (7.6%) we
      did observe small parafoveolar retinal pigment epithelium defects and in 1 case
      (1.3%) distinct pigment epithelium atrophy of the posterior pole. No comparable
      findings were observed in the control group. CONCLUSION: Compared with the
      examination results of the control group, in the patients with intermediate and
      chronic Chagas' disease we observed an accumulation of retinal pigment epithelium
      defects, which, however, did not cause a significant loss of vision.

PMID- 9181838
TI  - [Measuring saccades in endocrine orbitopathy].
AB  - Thyroid-associated ophthalmopathy (TAO) is evaluated mainly by orthoptic
      examination and morphometric parameters such as ultrasound, CT scanning or
      magnetic resonance imaging. Inflammatory changes of the extraocular muscles lead
      to an impairment of eye movement. Recent evidence suggests that saccades are
      altered by changes to the extraocular muscles. Although of potential interest,
      this phenomenon has so far received little attention. To determine the role of
      saccades as a potential diagnostic tool for assessing the function of the
      affected muscles, we have begun to analyze saccadic parameters in patients with
      TAO. Preliminary results of this study are reported in the present paper. For
      registration of both horizontal and vertical eye movements, we used the "Ober-2
      Apparatus," which uses the infrared technique. Horizontal and vertical saccades
      with an amplitude of 10 degrees were analyzed in 20 healthy persons and 30
      patients suffering from TAO. Patients showed changes in the quality of saccades,
      such as the appearance of glissades and additional correctional saccades as well
      as quantitative changes, such as an increase in the maximum speed and latency.
      Our current data suggest the presence of saccadic alterations in TAO. Our ongoing
      studies are designed to evaluate whether characteristic changes can be assigned
      to certain stages of the disease and whether assessment of saccadic changes in a
      promising tool for early detection and functional follow-up in patients with TAO.

PMID- 9181839
TI  - [Reproducibility of the pattern electroretinogram].
AB  - The pattern ERG (PERG) is used as an indicator of retinal ganglion cell function.
      Up to now, reports on the reproducibility of the PERG have been contradictory. We
      investigated the reproducibility under the conditions of the forthcoming ISCEV
      guidelines for the PERG. We simultaneously recorded the PERG and VEP in 42 eyes
      of 21 subjects to phase-reversing checkerboard stimuli with DTL electrodes. Both
      transient (2 rps) and steady-state (16 rps) stimulation was employed. The check
      sizes were 0.4 degree, 0.8 degree and 16 degrees, the mean luminance 45 cd/m2,
      the contrast 98%, and the field size 32 degrees x 27 degrees. Measurements were
      repeated at the same time of day after 1 week. In addition, we compared two
      different electrode positions in 16 eyes: (1) across the cornea along the lower
      lid; and deep in the conjunctival sac. With position (1) the amplitudes were
      found to be higher by 20% than (2). We calculated the coefficient of variation
      (CV) of amplitude as a measure of reproducibility. CV was 7 +/- 1% for the steady
      state PERG, 9 +/- 1% for the transient PERG, 12 +/- 2% for the steady-state VEP
      and 14 +/- 3% for the transient VEP. For the latency of the PERG, the
      intersession CV was found to be 1.5%. Amplitude reproducibility was somewhat
      higher under steady-state as compared to transient stimulation; we attribute this
      to the high noise rejection of the Fourier analysis. Altogether, the amplitude
      reproducibility of the PERG is somewhat higher than that of the VEP.

PMID- 9181840
TI  - [Foveal deuteranoptic opposing color vision].
AB  - By means of a visual tristimulus colorimeter according to Guild-Bechstein, the
      following items were determined for a male deuteranopic observer on a foveal,
      i.e. 2 degrees diameter visual field: (1) the deuteranopic missing color, by
      means of the perceptual criterion "indistinguishably equal", (2) the neutral
      zone, by means of the perceptual criterion "neither blue nor yellow," (3) the
      alychne trace, by means of the perceptual criterion "heterochromatically equally
      bright." The evaluation in the chromaticity chart resulted in two straight lines
      forming a dichromatic pencil, the deuteranopic missing color providing the
      carrier point (vertex). These two straight lines represent the referential
      chromaticities of a deuteranopic opponent color system.

PMID- 9181841
TI  - [EOG in adult vitelliform macular degeneration, butterfly-shaped pattern
      dystrophy and Best disease].
AB  - OBJECTIVES: We evaluated the EOG in the various stages of foveomacular dystrophy
      (also called adult-onset vitelliform macular dystrophy) and compared these
      findings to those in Best's disease and butterfly-shaped dystrophy. PATIENTS AND
      METHODS: The records of 49 patients (98 eyes) in whom foveomacular dystrophy had
      been diagnosed by ophthalmoscopy or by fundus photographs and fluorescein
      angiography were retrospectively reviewed. Fifty-seven eyes were followed up
      (range 1.1-20 years, mean 10.4 years). EOG was elicited according to the method
      of Rohde and Taumer. The results were compared to those in Best's disease and
      butterfly-shaped dystrophy. RESULTS: In foveomacular dystrophy all mean EOG
      values were within normal ranges. There was no difference between the various
      stages of the disease. In Best's disease only the dark-adapted steady-state
      potential was in the normal range. The amplitude and the implicit time of the
      light peak were significantly different from those in patients with foveomacular
      dystrophy (P < 0.05 ANOVA). In butterfly-shaped dystrophy all the EOG parameters
      were normal. The ratio of the light peak to steady-state potential was
      significantly lower in foveomacular dystrophy than in butterfly-shaped dystrophy.
      CONCLUSION: In foveomacular dystrophy the mean values of the EOG were normal.
      Despite the morphological similarity we found more pronounced
      electrophysiological differences from Best's disease than from butterfly-shaped
      dystrophy.

PMID- 9181842
TI  - [New blindness incidents in Wurttemberg-Hohenzollern].
AB  - Blindness causes human suffering and high social costs. Preventive measures are
      necessary. Virtually all blind people are registered with the social services.
      Data from these institutions may help in (long-term) planning for blindness
      prevention. MATERIAL AND METHODS: The present investigation analysed data from
      the social services of the region Wurttemberg-Hohenzollern. The files contained
      information on ocular status, year of birth, district, and sex of newly blind
      subjects of the year 1994. RESULTS: Two thirds (66.8%) of newly blind subjects
      are women. About half (47.8%) of all subjects are over 80 years of age. The most
      frequent causes of blindness are: macular degeneration, 33.7%; diabetic
      retinopathy, 17.3%; glaucoma, 13.8%; and high myopia, 6.6%. CONCLUSIONS:
      Blindness is increasingly a problem of high age. Diabetic retinopathy and
      glaucoma are still major causes of blindness. For these diseases blindness
      prevention is conceivable. Thus co-ordinated blindness prevention activities
      should focus on diabetic retinopathy and glaucoma.

PMID- 9181843
TI  - [Scanning electron microscopy studies of human lenses].
AB  - BACKGROUND: In order to better understand the mechanism of tearing of the human
      lens capsule during circular capsulorhexis, scanning electron microscopic (SEM)
      examinations were made particularly of the rhexis edge. MATERIALS AND METHODS:
      Anterior segments from cornea donor eyes, as well as capsular pieces extracted
      during cataract surgery, were studied after fixation in glutaraldehyde, critical
      point drying, and sputtering with gold. RESULTS: The edges of the capsulorhexis
      were found to be very regular even in the area of zonular attachment. Neither the
      surface of the lens capsule nor the edge of the rhexis itself indicated any
      morphological influence on the direction of tearing. CONCLUSION: From the results
      we conclude that the rhexis of the lens capsule is only directed by the forces
      applied and not by particular morphological structures. To avoid radial tears, a
      deep anterior chamber, resulting in a relief of the anterior zonular portion
      seems most important. This minimizes radial forces on the anterior lens capsule,
      which provides the best condition for a safe rhexis.

PMID- 9181844
TI  - [Therapy refractory marginal keratoconjunctivitis in a child. Wegener's
      granulomatosis in a child with initial manifestation in the eye].

PMID- 9181846
TI  - [Computer applications in ophthalmology].

PMID- 9181845
TI  - [Filtering glaucoma operations. Can growth factor blockers replace
      antimetabolites?].

PMID- 9181847
TI  - [Gram-negative virulent bacterial lipopolysaccharide: role in infection and
      immunity].
AB  - The paper discusses the data available in the literature on the studies on
      lipopolysaccharides (LPS) of bacteria which show their different virulence. A
      comparative study of the chemical composition and structure of LPS of the
      bacteria fails to detect any great difference, but they differ in their
      biological, especially immunobiological properties. It is suggested that the
      differences are associated with LPS conformation, chiefly its lipid moiety and
      ion-coordinating processes and free radical reactions are involved in the
      conformation. Examining just these phenomena may made advances in further studies
      of virulent bacterial LPS and possibilities of its use while designing new
      generation vaccines.

PMID- 9181848
TI  - [Improvement of microbiological diagnosis of dysbacteriosis].
AB  - The study was undertaken to improve transport and selective culture media and a
      testing scheme for dysbacteriosis. Great emphasis is laid on methods for
      isolating and identifying the nonclostridial anaerobes which are the major
      component of the normal human intestinal microflora. The following media were
      proposed: a) a sterility-checking-up medium, hemin, vitamin K1, cysteine, and
      twin 80 was for transportation of samples to a laboratory; b) anaerobic blood
      containing agar with selective additives (kanamycin and bile) for isolation of
      bacteroids; c) a propionic acid-containing medium for isolation of
      bifidobacteria; d) a acetic acid-containing medium for isolation of
      lactobacteria. The use of the above culture media, microanaerostats, and three
      component gas mixture substantially enhanced the efficiency of microbiological
      diagnosis for intestinal dysbacteriosis.

PMID- 9181849
TI  - [Role of dysbacteriosis in the development of surgical infection].
AB  - The intestinal microflora was examined in 230 patients operated on for abdominal
      abnormalities and injuries. There were profound intestinal microbiocenotic
      impairments as appeared as lower bifidobacteria, intensive growth of
      opportunistic (coccal) microorganisms. A direct relationship was established
      between the severity of dysbacteriosis and the incidence of pyoinflammatory
      complications in the postoperative period. The use of live bacterial preparations
      in the complex therapy of patients with expected and emergency abdominal diseases
      or injuries reduced the number of pyoinflammatory complications and improved the
      therapeutic outcomes of patients with peritonitis.

PMID- 9181850
TI  - [Factors of intestinal microflora persistence in dysbacteriosis].
AB  - The persistent properties of the intestinal microflora as a mechanism of
      adaptation to the host's antimicrobial factors are substantiated. The results of
      determination of antilysozyme and anticomplementary activities and the
      inactivating abilities of the bactericidal component of interferon in enteric
      bacteria isolated in intestinal dysbacteriosis are outlined. Changes were found
      in the population structure of the Escherichia flora in relation to the severity
      of dysbacteriosis and a high prevalence of persistent signs were revealed in
      enteric bacteria. There was a correlation between the persistent signs of
      bacteria and the severity of intestinal microbiocenotic abnormalities. The
      factors of microbial persistence are proposed to be used as markers of a
      dysbiotic process.

PMID- 9181851
TI  - [Analysis of ordinary microbial relationships in human colonic dysbacteriosis].
AB  - A relationship between the qualitative and quantitative characteristics of
      representatives of the normal microflora in biocenosis of the colonic lumen (CL)
      was studied in 18 patients with subacute bacterial endocarditis, 18 patients with
      rheumatic heart disease, 13 with chronic renal failure and 50 healthy individuals
      without clinical signs of dysbacteriosis. The number of intermicrobial
      relationships was found to be rather small both in health and in disease.
      However, a disease shows a considerably greater number of different relations,
      synergic ones in particular. Analysis indicated that in the conditions under
      study 72 to 93% of relations that were realized in the healthy human CL biotope
      disappeared and the established intermicrobial relationships were found 86-97%
      quite new. Summing up, the authors have concluded that, first, the CL microflora
      exists under the conditions of excess nutrient substrate and is not a factor of
      self-regulation, second, changes in the body's metabolic systems are primary in
      the diseases examined, which the normal lumenal microflora is responsive to.

PMID- 9181853
TI  - [Immunomodulating action of eubiotics].
AB  - The study was undertaken to study the immunomodulating action of 3 bacterial
      agents: bifidumbacterin, acylact, and biosporine used in various abnormalities
      accompanied by intestinal dysbacteriosis. Surveys were made of children
      permanently residing in the radionuclide-contaminated areas of the Bryansk
      Region, those from northern areas of the Russian Federation, those who suffered
      from atopic dermatitis; adult patients with severe systemic disease (chronic
      postinfection polyarthritis); chronic adult patients with spinal injury due to
      compression fractures of the spinal cord. The immunological parameters in all the
      above patient groups were shown to differ in the lower absolute or relative
      counts of most lymphocytic populations. The addition of bacterial drugs into
      their therapy promoted normalization of the intestinal microflora and led to
      improvement or complete normalization of immunological parameters. With this,
      bifidumbacterin and acylact were demonstrated to be potent, but mild
      immunomodulators as they significantly improved or normalized the status of the
      baseline suppressed immune system and virtually failed to affect normal
      immunological parameters. The earlier data obtained with biosporine provide
      evidence for that this bacterial agent has immunomodulating activity; however, it
      is necessary to comprehensively study its effects on the immune system in health
      and in disorders typical of various abnormalities.

PMID- 9181852
TI  - [Problems in drug prevention and treatment of endogenous infection and
      dysbacteriosis].
AB  - Dysbacteriosis is an important pathogenetic condition in the development of
      endogenous infection whose treatment and prevention are among the most topical
      and challenging problems. The common cause of dysbacteriosis is antibiotic
      therapy and prevention of surgical infection. Antibiotic therapy should be
      performed in accordance to strict indications, with compliance of rational
      regimens and methods for using drugs. Adequate local and parenteral drugs should
      be given in wound infection. To prevent endogenous infection, selective
      gastrointestinal decontamination (SD) that requires bacteriological surveillance
      of the patient's intestinal microflora and the environment, as well as the use of
      eubiotics. In critically ill patients with multiple injuries, in patients on
      artificial pulmonary ventilation, other individuals at risk SD is highly
      effective, in which oral of intragastric antibiotics which are intestinally
      unabsorbable and active against only anaerobic opportunistic microbes were added
      by the same agents for the oral cavity and by lactic acid bifidumbacterin. The
      new biological drug Bifilys that contains the optimum balanced ratio of
      bifidobacteria and lysozyme and provides a prompt correction of microbiocenosis,
      local immunity, and intestinal function is highly effective in the treatment and
      prevention of dysbacteriosis. Electrochemically activated solutions are also
      promising in treating dysbacteriosis and digestive infections. There are
      available original Russian antiviral synthetic and natural agents to make drug
      therapy and prevention of viral infections frequently complicating the status of
      weak patients.

PMID- 9181854
TI  - [Role of intraspecific phenotypic diversity in the ecology of escherichia coli
      and staphylococcus aureus].
AB  - Investigating a complex of biological characteristics, including the inactivating
      ability of some antiinfectious resistance agents (lysozyme, complement,
      immunoglobulins, the bactericide component of interferon) in 229 and 257 E. coli
      and S. aureus strains, respectively, isolated from various sources has revealed
      the phenotypical polymorphism in the populations of these microorganisms, whose
      degree and specific features may be characterized by the indices of biological
      diversity and by the spectra of dominant biological profiles. Interpopulational
      variability in the bacteria was found to be determined by the specific features
      of their colonized ecotopes and to reflect the level of their adaptation to their
      inhabitance. There is a view of the organizational structure of the bacterial
      species as a whole complex of discrete populations of microorganisms, which
      include representatives of phenotypically different clone lines that occupy the
      optimum and some marginal econiches whose relation is supported by migration
      processes.

PMID- 9181855
TI  - [Dysbacteriosis: topical medical problem].

PMID- 9181856
TI  - [The nature of hematopoiesis in animals with experimentally depressed immune
      system: natural and bifidumbacterin-induced recovery].
AB  - An attempt was made to examine the regulatory effect of bifidumbacterin on the
      recovery of immunological and hemopoietic homeostasis in mice. Bifidumbacterin
      feeding to healthy animals had no effect, except for the below-normal values
      reaching the statistically mean characteristic of mice of this strain.
      Bifidumbacterin stimulated lymphoiesis in animals immunocompromized by the
      administration of antilymphocytic antibodies or radiation, but the values being
      no higher than the normal ones. The same action was seen with erythropoiesis
      during postradiation loss of red blood cells. The activation or suppression of
      erythro- or myelopoiesis, which was not caused by direct damage to these cellular
      populations, but which occurred with the activation of nonspecific T helpers or T
      suppressors in impairments or recovery of the count of circulating mature
      lymphocytes under the action of bifidumbacterin, was blocked.

PMID- 9181857
TI  - [Use of Salmonellas as a vector in the designing of recombinant vaccines].

PMID- 9181858
TI  - [Recombinant probiotics: problems and prospects of their use for medicine and
      veterinary practice].
AB  - Approaches to designing a new probiotic class based on recombinant strains of
      bacteria that produce the predetermined therapeutic proteins are dealt with. The
      prospects of the approach are shown via studies of the biological properties of
      Bacillus subtilis 2335 strain transformed by the plasmid encoding the synthesis
      of human interferon alpha-2. The recombinant strain was demonstrated to preserve
      the high antagonistic activity of the parent culture (the bases of the probiotic
      biosporine) and to acquire marked antiviral properties due to interferon
      synthesis. The antiviral activity of the designed strain was shown by in vitro
      and in vivo experiments on experimental viral infections. By using this strain,
      the authors designed the new probiotic subaline, a promising biological agent for
      medicine and veterinary practice. Subalin has a number of advantages: it combines
      antibacterial and antiviral properties, is easy to use and prepare.

PMID- 9181859
TI  - [Morphology of myocardial adaptive responses to extreme environmental factors].
AB  - The paper deals with myocardial spatial reorganization under the influence of
      emergency environmental factors: low systemic temperature (-7 degrees C), single
      overheating (at 43 degrees C), long-term stay in the high mountains (3200 m above
      sea level) and after transportation to high latitudes (at 69 of the North). Among
      the changes in the ratio of major myocardial tissue components, 2 stages are
      identified: 1) that is characterized by profound changes in the volume and
      surface-to-volume ratios of major tissue components (capillaries and
      cardiomyocytes in particular); 2) that shows a tendency to normalization of
      tissue architectonics. These changes in tissue reorganization is likely to be
      caused by stress responses and to reflect some structural mechanisms of a
      nonspecific response to emergency. In contrast, the intracellular spatial
      reorganization of cardiomyocytes is characterized by persistently recorded
      disproportional changes in the volume ratios of bulk organelles (mitochondrias
      and myofibrills in particular). The differences found in the changes of tissue
      and intracellular spatial reorganization reflect the basic features of spatial
      and-temporal organization of regenerative processes in the parenchymal cells
      (cardiomyocytes) and stromal components.

PMID- 9181860
TI  - [Experience with integration of research institutes if the Russian Academy of
      Medical Sciences with the departments if higher educational establishments of the
      IM Sechenov is an effective type of teaching and research intensification].

PMID- 9181861
TI  - [Early stages of development of infectious process and two-faced role of normal
      microflora].

PMID- 9181862
TI  - [The effect of affinity on the type of action of ammonium compounds on skeletal
      muscle cholinoreceptors].
AB  - The dependence of the mode of action (agonist or antagonist) of ammonium
      compounds on the acetylcholine receptors (AcR) of frog skeletal muscles on their
      affinity for AcR was studied in experiments on musculus rectus abdominis of Rana
      temporaria frogs. The mode of action of the compounds proved to be dependent on
      the degree of the affinity and on the character of their intermolecular
      interactions with the receptors. The affinity of compounds of the polymethylene
      bis-trimethylammonium series is determined by electrostatic and hydrophobic
      interaction with the AcR. In this case compounds with a low affinity constant
      (Ka) are poor antagonists, compounds with high Ka are strong antagonists, and
      compounds with intermediate Ka are partly agonists. Compounds whose affinity is
      determined not only by the electrostatic and hydrophobic but also by the dipole
      dipole interaction (series D compounds) are pure and strong agonists.

PMID- 9181863
TI  - [Nimodipine, nifedipine and the cerebrovascular effects of serotonin].
AB  - Experiments on rats with the use of ultrasonic techniques demonstrated that
      serotonin causes an initial significant decrease in the blood flow in the channel
      of the middle cerebral artery followed by a mild increase in the blood supply to
      the brain. It was shown in in vivo experiments that nimodipine and nifedipine do
      not prevent the development of serotonin-induced constriction of the vessels of
      the middle cerebral artery channel. At the same time, the cerebrovascular effects
      of nimodipine and nifedipine are significantly weakened under the action of
      serotonin.

PMID- 9181864
TI  - [The mechanisms of the effect of a high extracellular sodium concentration on the
      contractile activity of the isolated rat heart].
AB  - Increase in the extracellular concentration of sodium (from 140 mM to 200 mM)
      causes an initial increase in the developing left-ventricular pressure which is
      replaced by increase of the amplitude of contractions by 40-50% in comparison
      with the initial condition. Lithium chloride (60 mM) did not cause similar
      changes. The initial diminution of myocardial contractility under the effect of a
      hypersodium medium was not sensitive to verapamil, ethmosin, lidocaine, caffeine
      or the Na-H exchange blocker hexamethylenamyloride (HMA). Verapamil (0.1 microM)
      or HMA (1 microM) did not influence the increase in the developing pressure
      induced by the hypersodium medium. The favorable inotropic effect of the
      hypersodium medium was manifested after arrest of the heart with verapamil (2
      microM). Caffeine (2 microM), ethmosin (1 microM) or lidocaine (100 microM)
      weakened the favorable effect of the hypernatrium medium.

PMID- 9181865
TI  - [The participation of the central and peripheral kappa-opiate receptors in the
      mechanism of the anti-arrhythmia action of benzeneacetamide derivatives].
AB  - When injected intraperitoneally in a dose of 8 mg/kg, U-62066, the selective
      agonist of kappa-opioid receptors, exhibits antiarrhythmic properties in
      epinephrine-induced arrhythmias in rats. In cerebroventricular injection, the
      kappa-agonists U-50,488 and [D-ala2]-dynorphin A(1-13) manifest proarrhythmic
      properties. Preliminary administration of the kappa-antagonist nor
      binaltorphimine completely removes the proarrhythmic and antiarrhythmic effect of
      kappa-agonists. The antiarrhythmic effect of U-62006 is believed to be associated
      with activation of peripheral kappa-receptors.

PMID- 9181867
TI  - [The anti-ulcer action of zinc sulfate in models of acute and chronic
      ulcerogenesis in the rat duodenum].
AB  - The 5-day pretreatment of rats with zinc sulfate (50 or 150 mg/kg/day per os)
      significantly reduce the rate, the number, and area of cystamine-induced duodenal
      lesions in rats. Pretreatment with zinc sulfate in a dose of 15 mg/kg/day over a
      5-day period or single administration of zinc sulfate (50 mg/kg) did not markedly
      reduce the above-mentioned lesion parameters. The administration of zinc sulfate
      (50 or 150 mg/kg/day per os) during 7 days results in a dose-dependent,
      significant decrease in the area of chronic acetate-induced gastric and duodenal
      lesions in rats. The results of clinical and experimental study indicate that
      zinc-containing compounds can be successfully used both for prophylaxis and
      treatment of duodenal ulcer.

PMID- 9181866
TI  - [The pharmacological effect of betapressin in hypertension].
AB  - The work analyses the results of treating 20 hypertensive patients with (stage I
      II) with betapressin. The drug is shown to be active in causing a significant
      decrease of systolic and mean arterial pressure. Its hypotensive effect is
      associated with essential decrease of peripheral vascular resistance. This
      circumstance, as well as acceleration of the heart rhythm, leads to increase of
      the cardiac output. Betapressin is recommended for monotherapy of patients
      suffering from stages I-II hypertension with eu- and hypokinetic types of
      hemodynamics.

PMID- 9181868
TI  - [An experimental study of the pharmacokinetics of a new pediatric drug form-
      Paravit tablets].
AB  - A comparative study of Paravit and paracetamol pharmacokinetics is carried out on
      impuberal rabbits. It has been shown that ascortic acid present in Paravit
      enhances the bioavailability of paracetamol. The relative bioequivalence of
      Paravit is found to be 136.7%.

PMID- 9181869
TI  - [Differences in the effects of piracetam and fenazepam in emotional stress caused
      by the spatial reversal of a habit].
AB  - Emotional stress was caused in rats by changing the location of the gate in the
      shuttle chamber through which training had been accomplished in the previous
      experiments. The procedure led to disorder of the avoidance response (AR) and
      increase of intertrial responses (ITR). Phenazepam (0.1 mg/kg) prevented increase
      in the number of ITS. Piracetam (300 mg/kg) reduced the sharp growth of ISR but,
      in contrast to phenazepam, it provided a higher level of AR reproduction. The ISR
      were greater in piracetam than in phenazepam administration. The obtained results
      show that the suggested model allows the difference in the effects of piracetam
      and phenazepam to be disclosed.

PMID- 9181870
TI  - [The toxicity and biological effects of organophosphorus epoxides].
AB  - In the series of glycidylic ethers of alkylophosphoric and methylphosphoric acids
      three types of compounds have been identified: those possessing
      anticholinesterase, narcotic, and antineoplastic activity. Monoglycidylic ethers
      of diethyl- and diisopropylphosphoric acids and diglycidylic ether of
      ethylphosphoric acid caused intoxication of animals with the cholinergic
      excitation syndrome, and in vitro in a concentration of 1 mmol/liter strongly
      inhibited cholinesterase, stimulated the motor activity of an intestinal segment,
      but did not demonstrate cytotoxic activity in relation to NK/Ly strain tumor
      cells. Monoglycidylic ethers of di-n-propyl-, di-iso-butyl, and di-n-butyl
      phosphoric acids as well as diglycidylic ethers of n-butyl- and iso
      amylphosphoric acids caused a "hypnotic state" in the animals, suppressed the
      motor activity of an isolated intestinal segment, considerably increased the
      number of diffusely stained by Aizenman's [correction of Aisenmanns'] method
      cells of ascitic NK/Ly tumor in vitro, but poorly inhibited the growth of this
      tumor in chemotherapeutic experiments. Diglycidylic ethers of methyl-, n-propyl-,
      iso-butylphosphoric, and methylphosphonic acids caused poisoning of the type of
      intoxication by alkylating agents, weakly influenced cholinesterase activity, did
      not change the character of contractions of the intestinal segment. In vitro they
      caused a strong cytotoxic effect, but delayed the growth of the NK/Ly tumor
      treated animals by 84-100%. The possibility of the phosphororganic epoxides under
      study taking part in the reactions of alkylation and phosphorylation is
      suggested.

PMID- 9181872
TI  - [The phospholipid composition of the liver and the glycolipid spectrum of the
      brain in rats administered cyanamide].
AB  - The effect of cyanamide on the liver phospholipids and brain glycolipids was
      studied (on rats). It was found that cyanamide (60 mg/kg, intraperitoneally)
      increased the amount of liver lysophosphatidylcholine, sphingomyelin, cardiolipin
      and decreased phosphatidylcholine and phosphatidylethanolamine. Similar but more
      pronounced alterations of liver phospholipids were found after ethanol
      administration 91 g/kg, 20% solution intraperitoneally) under the influence of
      cyanamide. After cyanamide and its combination with alcohol brain concentrations
      of sulfatides I, II as well as cerebrosides l, II and III decreased.

PMID- 9181871
TI  - [The effect of perftoran on the resistance of mice to GABA receptor antagonists
      and on the antidote activity of anticonvulsant agents].
AB  - Perfluorane (a phenobarbital-type inducer of the microsomal enzyme system) raised
      the resistance of mice to the toxic effect of picrotoxin and bicucullin in 7 days
      after injection. The antidote effect of diazepam and phenobarbital increased
      under such conditions. In experiments in vitro a modulatory effect of perftorane
      on the central muscarine and benzodiazepine receptors was demonstrated.

PMID- 9181873
TI  - [The corrective action of limontar in metabolic disorders in the mother-fetus
      system caused by ethanol exposure during pregnancy].
AB  - It was established in experiments on nonbred albino rats that injection of
      limontar (1 mg/kg) in the fetal period of pregnancy in alcoholic intoxication (6
      g/kg) leads to weight loss by the female, normalization of the character of
      behavior and metabolic shifts in the organism, and removal of the symptoms of
      excitation of the sympathetic link of cardiovascular system regulation. No
      harmful effect of limontar on the mother-fetus biosystem was detected.

PMID- 9181874
TI  - [The effect of cholecystokinin octapeptide on ethanol-induced changes in motor
      activity and in dopamine metabolism in the nucleus accumbens of the rat brain].
AB  - The effect of intraventricular injection of cholecystokinin-octapeptide (CCK-8)
      in doses of 0.1875; 0.375; 0.75 and 1.5 micrograms/rat on the extracellular level
      of dopamine (DA) and its metabolites (DOPAC and HVA) after intraperitoneal
      injection of 1.5 g/kg ethanol was studied by microdialysis in n. accumbens of the
      brain of freely moving rats. CCK in a dose of 0.75 mg had no effect on the DA
      level, but significantly reduced the ethanol-induced increased DOPAC and HVA
      level. The effect of intraventricular injection of 0.75 microgram/rat CCK-8 on
      the motor activity of rats after intraperitoneal injection of ethanol (1.5 g/kg)
      was studied by the open field method. CCK-8 blocked the ethanol-induced
      inhibition of rat motor activity.

PMID- 9181876
TI  - [The protective action of ethomersol in acute hypobaric hypoxia and during the
      recovery after it].

PMID- 9181875
TI  - [The effect of lithium oxybutyrate on the development of the fetus and progeny in
      alcoholic intoxication of male rats].
AB  - The effect of lithium hydroxybutyrate on the development of the fetus and
      offsprings was studied on a model of alcohol intoxication of male rats. Under
      such conditions lithium hydroxybutyrate relieved completely the negative action
      of alcohol on the reproductive function, according to all parameters. The
      learning ability of the offsprings and their behavioral disorders in a stress
      situation caused by alcohol were normalized. Two-week administration of 100 mg/kg
      lithium hydroxybutyrate had no negative effect on the embryonal and postnatal
      development of the offsprings.

PMID- 9181877
TI  - [A method for selecting drugs that affect the rheological properties of the blood
      in vitro].
AB  - For the selection of compounds affecting the hemorrheologic status a method for
      reproducing disorders of blood rheologic properties in vitro was developed. It
      consists in 60-min incubation of blood at 42 degrees C. The hemorrheologic effect
      of quercetin under such conditions was studied and a dependence of the effect of
      quercetin on blood viscosity and red cell aggregation on the drug concentration
      was revealed.

PMID- 9181878
TI  - [The mechanisms of action of ketamine].
AB  - The review systematizes the latest data on the main mechanisms of realization of
      some pharmacological properties of ketamine which are particularly valuable in
      the treatment of many diseases and conditions. The authors present the main
      aspects of the ketamine effect on the central mechanisms of anesthesia and
      hemodynamics and give the characteristics of its neuroprotective action. It is
      shown that these effects are realized also at the cost of the non-competitive
      blockade of the NMDA receptors in the central nervous system.

PMID- 9181880
TI  - [The vascular effects of estrogens and the hormonal replacement therapy of
      climacteric disorders].

PMID- 9181881
TI  - Vth High Pressure Biology Meeting. St Petersburg, Russia, 7-9 July 1997.
      Abstracts.

PMID- 9181879
TI  - [The effect of lamotrigine and carbamazepine on the development of the audiogenic
      seizure reaction in rats of the Krushinskii-Molodkina strain].
AB  - The effect of Lamotrigine and carbamazepine on the development and character of
      the epileptiform seizures after strong sonic stimulation were studied on
      Krushinskii-Molodkina line of rats. Both drugs manifested a dose-dependent
      increase in the latency of motor reaction Lamotrigine administration in the dose
      range of 5-40 mg/kg, i.p., resulted in a moderate decrease in the seizure
      intensity preventing predominantly the tonic component of the seizure and failed
      to modify the character of convulsive reaction. Carbamazepine administered in
      doses of 7.5-30 mg/kg effectively prevented the epileptiform seizures. The "two
      wave" motor reaction was observed in 15% of carbamazepine-treated rats.

PMID- 9181882
TI  - [LGM inferior vena cava filters--follow up 50 patients].
AB  - In the Department of Medicine at the Institute of Tuberculosis and Lung Diseases
      50 LGM inferior vena cava filters have been inserted since 1993. Indications for
      filters placement were as follows: recurrent pulmonary embolism (PE) despite
      anticoagulation-16 patients (pts), severe bleeding complications of thrombolytic
      or anticoagulant therapy-9 pts, contraindications for thrombolytic and/or
      anticoagulant treatment-3 pts, massive PE-6 pts, chronic thromboembolic-major
      vessel pulmonary hypertension (CTEPH)-18 pts, extensive deep vein thrombosis of
      lower limbs or vena cava inferior in patients with urgent indications for surgery
      10 pts. In every patient diagnostic procedures were performed after 1, 3, 6, 12,
      24 and 36 months of follow-up period. Only one non-fatal episode of recurrent PE
      was documented. Other complications were rare and insignificant. The LGM inferior
      vena cava filters are effective and safe in such selectively chosen group of
      patients.

PMID- 9181883
TI  - [Implantation of LGM inferior vena cava filters in patients with chronic
      pulmonary hypertension during a course of major vessel thromboembolism-
      observation of 18 patients].
AB  - CTEPH have not been widely recognised until recently. Introduction of the new,
      sophisticated, non-invasive diagnostic tools accounts for rapid progress in that
      field. Patients with high pulmonary hypertension have a very poor prognosis.
      Medical treatment (vasodilators, anticoagulants) does not change outcome.
      Pulmonary thromboendarterectomy is the only therapeutic option for the patients.
      It is essential to prevent further episodes of pulmonary embolism both over the
      long term and during the high risk perioperative period by means of inferior vena
      cava filters. In the Department of Medicine, Institute of Tuberculosis and Lung
      Diseases 18 LGM ivc filters have been inserted in patients with CTEPH since 1994.
      In 7 patients PTE was performed-in 5 cases good result was achieved, 2 patients
      died after surgery. In the latter group 5 patients died mainly because of severe
      heart failure. Only one non-fatal episode of pulmonary embolism was observed. It
      should be concluded that the LGM ivc filters are safe and effective in preventing
      episodes of pulmonary embolism in patients with CTEPH.

PMID- 9181884
TI  - [Low doses of rtPA administered as a bolus in treatment of clinically acute
      massive pulmonary embolism].
AB  - 12 patients (7 male and 5 female) with confirmed pulmonary embolism (PE) with:
      angiography-5 cases, conventional contrast-enhanced CT-2 cases, echocardiography
      2 cases, autopsy-3 cases were diagnosed as clinically acute PE. Criteria of
      clinically acute PE were: cardiac arrest-1 case-2 cases, shock-1 case, acute cor
      pulmonale-9 cases and acute cor pulmonale with shock. All patients were treated
      with heparin, administered with therapeutic prolongation of aPTT. Clinically
      acute PE (if possible confirmed with angiography, TC and/or echocardiography) was
      treated with rtPA administered in 10 minutes lasting bolus in doses 0.6-0.8 mg
      per kg of body weight (50 mg of rtPA during 10 minutes administered into
      peripheral veins). In 9 patients with pulmonary hypertension, significant
      decrease of tricuspidal gradient (measured echocardiographically during several
      hours after administration of rtPA) was documented. Improvement in PaO2, SaO2 and
      decrease of heart rate and respiratory rate were also achieved. No serious
      bleeding complications were observed after mentioned treatment. Control
      investigations (conventional contrast-enhanced CT and spiral CT) performed
      several days after rtPA administration revealed thrombus in pulmonary artery. We
      conclude: I rtPA administered in bolus simultaneously with heparin significantly
      decreased pulmonaryhypertension; rtPA administered simultaneously with heparin is
      safe method of treatment of PE; hemodynamic improvement after administration of
      rtPA is not univocal with full fibrynolitic effect.

PMID- 9181886
TI  - [Pericardial syndrome in the course of pulmonary embolism in personal material].
AB  - Dressler-like syndrome has been described in about 3-4% of patients after
      pulmonary embolism (PE). Out of 207 patients admitted to our hospital in whom the
      clinical diagnosis of PE was confirmed by scintigraphy, spiral computer
      tomography and angiography, in 19 patients (9.2%) pericardial fluid was detected
      and pericardial syndrome (PS) after PE was diagnosed. Other causes of
      pericarditis were excluded. Mean value of pericardial fluid in echocardiographic
      examination-behind left ventricular posterior wall was 3.84 mm (range 2-10 mm).
      No clinical or echocardiographic symptoms of cardiac tamponade were observed. In
      6 patients PS complicated clinically massive PE, in 3 patients-non-massive PE, in
      10 patients recurrent PE. In 6 patients fibrinolytic and in 13 patients heparin
      therapy was instituted. In 3 cases corticosteroids were given. No increase of
      pericardial fluid during fibrinolytic or heparin therapy was observed.
      CONCLUSIONS: 1. PS after PE is more frequent, than it was estimated previously 2.
      During therapy of PE the echocardiographic monitoring of the amount of
      pericardial fluid is mandatory 3. The clinician considering in similar situations
      the risk-benefit ratio of fibrinolytics and anticoagulants should not abstain
      from the use of these drugs in the presence of PS after PE, in cases with high
      probability of cardiac tamponade-pericardial catheter should be used.

PMID- 9181885
TI  - [Clinically silent pulmonary embolism in patients with proximal deep venous
      thrombosis].
AB  - In 18 patients with proximal deep venous thrombosis (PDVT) confirmed by
      phlebography, no symptoms and signs of pulmonary embolism (PE) were observed. All
      patients were treated with nadroparin. During first 6 days of treatment in all
      patients perfusion lung scans were performed. 8 patients (44.4%) of all group
      developed lung scans positive for PE (silent PE). Period of successful treatment
      of PDVT was 10 days. No evidence of recurrent PE were observed during the period
      of treatment. We conclude that: 1. Frequency of silent PE in patients with PDVT
      is very high-lack of symptoms and signs of PE does not exclude the presence of PE
      in this group of patients. 2. In all patients with PDVT perfusion lung scan
      should be performed even in cases with no symptoms and signs of PE. 3. Low
      molecular weight heparins administered subcutaneously are effective in treatment
      either silent PE or PDVT.

PMID- 9181887
TI  - [The value of measuring adenosine deaminase activity in pericardial effusion
      fluid for diagnosing the etiology of pericardial effusion].
AB  - The diagnosis of tuberculous pericarditis is difficult. The cultures of the
      pericardial fluid for M.tuberculosis are often negative. The determination of ADA
      activity in pleural fluid in TB patients /PTS/ is very useful. It seemed
      reasonable to measure ADA activity in pericardial effusion. ADA activity in
      pericardial fluid of 40PTS/19 women and 21 men/with large pericardial effusion of
      different etiologies who were treated in our institute in years 1988-1995 was
      investigated. The median age was 44 years. In each case the pericardiocentesis
      was performed. PTS were grouped as follows: group I-4 PTS with strongly suspected
      TB pericarditis, group II-32 PTS with malignancy and group III-4 PTS with
      miscellaneous diseases. In group I the mean ADA activity was 24U/I(3-60), in
      group II 18U/I (3-60) and in group III 18U/I (0-37) (with a cutoff value for ADA
      activity of 40U/I). It was definitive bacteriologic diagnosis of TB pericarditis
      in PTS of group I. Our observation does not confirm the earlier data about the
      high ADA activity in clinically suspected TB pericarditis without bacteriologic
      diagnosis. The value of ADA determination in pericardial fluid is its high
      specificity (97%) in excluding of TB etiology of pericardial effusion.

PMID- 9181888
TI  - [Evaluation of intrapericardial cisplatin administration in cases of recurrent
      malignant pericardial effusion and cardiac tamponade].
AB  - 30 consecutive patients with large malignant pericardial effusion (MPE) entered
      this prospective study. After pericardiocentesis and insertion of a polyurethane
      catheter, pericardial fluid was drained. Malignant etiology of pericardial fluid
      was confirmed by cytological examination. After confirmation of MPE cisplatin (10
      mg in 20 ml normal saline) was instilled over 5 minutes during 5 consecutive days
      directly into pericardial space. If fluid reaccumulation occurred the courses
      were repeated every 3 weeks. Treatment was considered successful if the patient
      with malignant effusion survived 30 days without recurrence of symptoms of large
      pericardial effusion and other interventions directed to the pericardium were
      required. Positive effect of intrapericardial treatment with cisplatin was
      achieved in 18 cases (60%). Mean period of response was 3, 7 months (+/-6).
      Cisplatin administered directly into pericardial space is effective and safe
      method of treatment of recurrent MPE. Sclerosis of the pericardial space is rare
      complication connected with CP. Positive effect of CP can depend on improvement
      of lymphatic drainage from heart. CP seems to be method of choice in intal
      intrapericardial treatment in patients with malignant cardiac tamponade and
      recurrent MPE in course of lung cancer.

PMID- 9181889
TI  - [Echocardiographic analysis of cardiac size and function in patients with severe
      obstructive sleep apnea].
AB  - The purpose of this study was to determine usefulness of non invasive
      echocardiographic measurements in patients with severe obstructive sleep apnea
      (OSA). Diagnosis of OSA was established by polysomnography. We investigated 18
      patients (16M, 2F), mean age 45 +/- 10 years, mean weight 114 +/- 16 kg and mean
      apnea/hypopnea index 69 +/- 23. Two-dimensional (2D) and Doppler echocardiography
      (DOP) was used to assess: 1. Systolic function of left ventricle by determination
      of cardiac output (CO), ejection fraction (EF), 2. Diastolic function of left
      ventricle by calculation of mitral early diastolic velocity to arterial velocity
      ratio (Ev/Av) and atrial flow to total mitral flow ratio (AF/Tf), 3. Right
      ventricle thickness in systole (RVWS) and diastole (RVWD), and its diastolic
      diameter (RVD), 4. Pulmonary arterial pressure (PAP) by evaluation of
      acceleration time in the pulmonary artery (ACT) and tricuspid regurgitation jet
      velocity (TR). Results (mean +/- SD): Co 6.67 +/- 2.0 L/min, EF 44 +/- 5.6%, RVWS
      10.9 +/- 1.3 mm, RVWD 6.7 +/- 1.1 mm, RVD 30.3 +/- 2.8 mm, Ev/Av 1.22 +/- 0.39,
      Af/Tf 0.38 +/- 0.11, AcT 121.4 +/- 20.3 ms. These data confirm that intermittent
      hypoxia and increased ventricular afterload cause both systolic and diastolic
      left ventricular dysfunction. Right ventricular hypertrophy found despite normal
      resting, wake, PAP could be probably attributed to transient pulmonary
      hypertension during repeatable nocturnal hypoxic episodes.

PMID- 9181890
TI  - [Euthyroid sick syndrome in patients with respiratory failure].
AB  - There have been report concerning decrease of thyroid gland hormones
      concentrations in respiratory diseases. The aim of this study was to estimate the
      influence of severe respiratory failure (RF) of Intensive Care Unit (ICU)
      patients on blood serum thyroid hormone concentration. The tests were carried out
      in 22 ICU- patients with partial or total RF in whom the relationship between
      PO2, pH, PCO2 and TT3, TT4, FT3, rT3, FT4 was tested. The obtained data indicate
      that: 1. In patients with RF ESS takes place, 2. ESS seems to be related to the
      decrease of PO2; statistically significant correlation between TT3, FT3, rT3, and
      PO2 exist, 3. The increase of TT3 serum concentration directly correlates with
      the improvement of clinical state of patients. The lowest TT3 concentrations were
      observed in "ante mortem" patients. This fact suggest the prognostic value of
      TT3, TT4 concentration measurements in patients with RF.

PMID- 9181891
TI  - [Examination of thyroxine conversion to triiodothyronine in the lungs
      (preliminary report)].
AB  - Presence of triiodothyronine's receptors has been confirmed in majority of cells
      constituting lung architecture. The purpose of the investigation is the
      estimation of the conversion of the thyroxine through examination the activity of
      deiodinase I in the lung. The material in the form of 2.0-3.0 g lung pieces was
      taken in therapeutic thoracotomy from patients with emphysema, and in non-small
      cell lung cancer (n.s.c.l.c.). The examination of the activity of deiodinase I in
      chronic pulmonary diseases can help to show one of the elements of euthyroid sick
      syndrome (e.s.s.). The correlation between the deiodinase I activity in
      neoplastic tissue and the extent of the process of n.s.c.l.c. may provide the
      necessary data about the behaviour of triiodothyronine receptors which are
      closely related to oncogenes. The deiodinase I activity may be considered as a
      marker of lung cancer.

PMID- 9181893
TI  - [Massive pulmonary artery embolism complicated by acute pulmonary heart disease].
AB  - 43-year old woman, with considerable overweight had been admitted to Intensive
      Medical Care Unit with suspicion of pulmonary embolism (PE). The patient had the
      limb immobilized in gypsum for last several weeks. This episode was tangled with
      recurrent thrombosis of deep veins in the left limb, treated with heparin and
      oral anticoagulants irregularly without sufficient control. Taking into
      consideration the data of anamnesis, clinical picture and the results of ECG,
      chest X-ray, gasometric and echocardiographic examination we got much closer to
      the recognition of PE. Our suspicion of PE was confirmed by the result of
      pulmonary angiography. Indications for thrombolytic treatment (r-tPA) had been
      established. During the following hours considerable improvement of general state
      was observed. The therapy was continued with constant drip infusion of heparin.
      No prolongation of therapeutic PTT was observed. The deficit of AT III was
      diagnosed. In this situation the patient was given AT III to obtain normalization
      of its level and therapeutic extension of PTT. Therefore there were settled
      indications for the operation of uterus with myoma changes. As the rich
      thrombolytic material in the leg's vein was found the patient was implanted LGM
      Filter, with excellent prophylactic effect (no PE in perioperative period). The
      clinical course of our case enabled to present most of diagnostic, therapeutic
      and preventive methods applied in venous thromboembolism.

PMID- 9181892
TI  - [Very low doses of tissue plasminogen activator in treatment of acute massive
      pulmonary embolism].
AB  - 57 years old woman with clinically acute massive pulmonary embolism confirmed by
      CT enhanced by contrast administration was treated with very low dose of rtPA
      (0.33 mg/kg) simultaneously with constant infusion of heparin (with therapeutic
      prolongation of aPTT). Excellent clinical effect and decrease of SPAP were
      achieved.

PMID- 9181894
TI  - [Severe pulmonary hypertension as a result of chronic pulmonary embolism to large
      vessels in a patient with recurrent multiple deep venous thrombosis].

PMID- 9181895
TI  - ["Pseudo-infarction pattern" in the course of pulmonary embolism].

PMID- 9181896
TI  - [Coronary artery vasospasm as a cause of chest pain in a patient with small cell
      lung cancer].
AB  - Case of 67 years old man with small cell lung cancer and coronary artery spasm
      has been presented. After administration calcium channel blockers and
      nitroglycerin very good therapeutical effect was achieved.

PMID- 9181897
TI  - Marrow transplantation in children: current results and controversies. Meeting
      #2. Hilton Head Island, South Carolina, USA, June 1-3, 1995. Proceedings and
      abstracts.

PMID- 9181898
TI  - Blood progenitor cell (BPC) mobilization studied in multiple myeloma, solid tumor
      and non-Hodgkin's lymphoma patients after combination chemotherapy and G-CSF.
AB  - For blood progenitor cell (BPC) mobilization, standard-dose VIP chemotherapy
      consisting of etoposide, ifosfamide and cisplatin has previously shown effective
      tumor reduction in solid tumor patients and sufficient progenitor cell
      mobilization for autologous blood cell transplantation. Mobilization chemotherapy
      regimens in multiple myeloma (MM) predominantly consist of melphalan or
      cyclophosphamide that induce marked cytopenia and considerable variability of
      progenitor cell collection. We studied whether in MM (n = 13), BPCs were
      efficiently and reproducibly mobilized with etoposide (500 mg/m2) and ifosfamide
      (1500 mg/m2), followed by daily s.c. G-CSF (5 micrograms/kg). In parallel,
      patients with solid tumors or non-Hodgkin's lymphomas (n = 28) treated with
      etoposide (500 mg/m2), ifosfamide (1500 mg/m2) and cisplatin (150 mg/m2) and
      identical dosing of G-CSF were analyzed. Before chemotherapy (day 0), on day 7
      after chemotherapy and on days of leukapheresis (day 9-14), leukocyte numbers,
      mononuclear cells (MNCs), CD34+ cells and coexpression of lineage markers were
      analyzed. Median blood leukocyte numbers were 28,100/microliters (range, 19,600
      40,400) on day 10 in myeloma patients and progressively declined over the next 4
      days. In contrast, in solid tumor and lymphoma patients leukocyte numbers
      constantly increased from a median of 12,400/microliters (range, 6000-22,000) to
      30,000/microliters (range, 16,300-63,300) between day 10 and day 13 after
      chemotherapy. Similar to leukocyte counts, median MNC numbers decreased in
      myeloma patients with successive leukaphereses, but steadily increased in solid
      tumor and lymphoma patients over the same period. CD34+ cell numbers in the blood
      peaked between day 9 and 11 (median: 40/microliters) in myeloma patients and then
      declined. In the solid tumor and lymphoma group, median CD34+ counts in the blood
      peaked on day 12 after mobilization chemotherapy (median: 100/microliters). The
      median CD34+ yield per leukapheresis in the myeloma group was 2.2 x 10(6)/kg
      (range, 1.5-4.7) on day 10, and fell steadily to 0.95 x 10(6)/kg on day 12,
      whereas in solid tumor/NHL patients median CD34+ cell yields remained between 3.5
      and 3.7 x 10(6)/kg from day 10 to day 12 after mobilization chemotherapy (P <
      0.001). To obtain sufficient cell numbers for engraftment a median of 2 (range, 1
      3) mobilization chemotherapy cycles were needed in MM compared to 1 (range, 1-10)
      in solid tumor or lymphoma patients, with a median of 5 (range, 2-8)
      leukaphereses in MM compared to 1 (range, 1-10) (P < 0.05). Taken together, we
      found that for patients with MM, VP16 and ifosfamide efficiently and predictably
      mobilizes progenitor cells into the PB with > or = 3 x 10(6)/kg CD34+ cells
      collected after one to two mobilization chemotherapy cycles.

PMID- 9181899
TI  - Physical properties of casts prepared from disinfected alginate.
AB  - The dimensional accuracy, surface hardness and reproduction of surface detail of
      stone casts produced from alginate impressions treated with 4.65% sodium
      hypochlorite, were investigated. To test dimensional accuracy, a Reflex
      Microscope was used to compare casts from 10 untreated impressions with casts
      from 10 impressions immersed in the solution for 30 mins. Surface detail and
      hardness were investigated on casts produced from impressions of a master
      stainless steel plate with 10 micro-indentations of increasing size. Surface
      detail of the casts were assessed by observation and surface hardness by a
      Vickers Hardness Machine. The dimensional accuracy test showed no significant
      differences between the experimental and control groups. Surface detail was
      unaffected after immersion of up to 10 mins. Surface hardness decreased linearly
      with respect to immersion time, when this was greater than 5 mins.

PMID- 9181900
TI  - [Paroxetine in the treatment of premature ejaculation].
AB  - This study evaluated paroxetine as a possible treatment for premature
      ejaculation. Sixty two patients affected by primary premature ejaculation were
      randomly assigned to two groups. A and B, and treated with two different
      treatment schedules. Patients assigned to group A were treated with paroxetine 20
      mg p.o. daily for six months; patients assigned to group B were treated with
      paroxetine 20 mg p.o. daily for fourteen days, and than dose was reduced to 10 mg
      for a total treatment period of six months. Only one patient reported
      significative side effects (weakness). Positive clinical results were obtained,
      at the end of the treatment, in 89 per cent of group A and 88 per cent of group
      B. In patients with primary premature ejaculation, paroxetine represents, in our
      opinion, the best therapeutic option for its efficacy and lack of significant
      side effects.

PMID- 9181901
TI  - [Laser-assisted endoscopic resection: a new surgical technique for the treatment
      of benign prostatic hypertrophy. Preliminary results of a study involving 100
      patients].
AB  - This study was designed to assess the efficiency of 2 kind of laser prostatectomy
      devices in the treatment of Benign Prostatic Hyperplasia: a non contact technique
      versus a contact technique versus a contact one. From January 1994 to September
      1994, 100 patients were included in a randomized comparison of 2 laser
      prostatectomy devices with right angle firing laser fibers: a non contact
      technique with Urolase fiber (Bard) (50 patients) versus a contact technique with
      Fibertom fiber (Dornier) (50 patients). The Urolase fiber was used at 60 Watts
      power setting for 60 seconds and administered to each lobe at 2, 4, 8 and 10
      o'clock positions. The Fibertom fiber was used by dragging or the so called
      "painting" technique at 3 and 6 months with 3 parameters: Madsen symptom scores,
      peak urinary flow rates and post-void residual urine volumes. Operative morbidity
      rate was 9%. No difference in morbidity between both fibers. No blood transfusion
      was required in any case. Statistical analysis of the aforementioned parameters
      shows a p-value of < 0.001 for all parameters. Comparing the 2 different fibers,
      there was no statistical difference in outcome for any of these parameters. From
      this study we conclude that the preliminary results achieved, using the Urolase
      and the Fibertom fiber, are equivocal and interesting. However, a long term
      follow-up is necessary to evaluate the definitive efficiency of laser
      prostatectomy and to determine the optimal procedure.

PMID- 9181902
TI  - [Our experience with prostatic incision (TUIP) with local anesthesia].
AB  - The Authors present their experience in the treatment of prostatic obstruction
      with bladder neck incision (TUIP) performed under local anesthesia. An Hulbert 6
      Fr endoscopic needle is used to infiltrate the prostatic area submitted to TUIP
      with 200 mg of Lidocaine 2%. The TUIP was done with a single deep incision at 7
      hours using a 24 Fr Iglesias resector with Collins device. 28 patients with an
      age range from 69 to 85 years (mean 74) affected by IPB in an obstructed fase
      were submitted to this procedure. Various parameters were achieved for the
      selection of the patients: urodynamic diagnosis of low urinary tract obstruction,
      prostatic volume less than 50 ml without important prostatic median lobe, high
      anesthesiological risk, absence of correlated vesical complications. A clinical
      follow up was done at 1-6 and 12 months. The results obtained showed a good
      compliance of the patients treated with satisfactory urodynamic patterns. The
      Authors conclude that this less invasive approach, in selected cases, is the
      treatment of choice not only for low invasivity and morbidity rate but also for
      the reduced time of catheterization, hospitalization and costs.

PMID- 9181903
TI  - [Stress urinary incontinence in women. Our experience with 218 cases].
AB  - From November 1992 to March 1994, in the Gynaecological ward of the Obstetrical
      and Gynaecological section of Cannizzaro Hospital, 218 patients suffering from
      urinary stress incontinence (U.S.I.) were observed. Using computerized clinical
      cards, U.S.I. was found in the 71.79% cases. From the clinical evaluation 38.39%
      of patients were found to be suffering from 1st degree bladder prolapse, 34.82%
      from 2nd degree bladder prolapse and 16.97% from, 3rd degree. 9.82% of the
      patients did not manifest signs of bladder prolapse. Therapy was mainly surgical.
      Burch colposuspension was carried out on 65 patients. When necessary a total
      hysterectomy and perineal plastic surgery was carried out. A Perrin-Leger bladder
      neck suspension was carried out on 10 patients and a Pereyra-Raz on 5. Given the
      varied aspects of U.S.I., the Authors would conclude that the best results are
      obtained by combining medical, surgical and rehabilitative treatment.

PMID- 9181904
TI  - [Clinico-experimental study of low-mineral "Monteferrante" water: monitoring the
      recurrences in patients with calculi].
AB  - This study presents the use and effects of a low mineral content water called
      "Monteferrante" on patients with urinary stone disease. We evaluated the blood
      and urine sample of twenty stone formers and ten healthy volunteers at three and
      six months after "Monferrante" water intake. Besides a benefic increasing of
      diuresis, the results show: an increase of: urinary magnesium (p < 0.001),
      urinary calcium (p < 0.01), uricosuria (p < 0.01), and reduction of: blood uric
      acid (p < 0.01), blood sodium (p < 0.05), azotemia (p < 0.05) and cholesteremia
      (p < 0.01). The "Monferrante" oligomineral water can be considered as an efficacy
      presidium in the prevention of stone disease.

PMID- 9181905
TI  - [Clinical response and survival in metastatic renal carcinoma during subcutaneous
      administration of interleukin-2 alone. Subcutaneous Il-2 in renal carcinoma].
AB  - Several clinical studies have demonstrated the efficacy of subcutaneous
      immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an
      attempt to better define the clinical parameters which may predict the efficacy
      of treatment, the present study shows the results obtained with subcutaneous Il-2
      alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously
      at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one
      immunotherapeutic cycle. In nonprogressing patients, a second cycle was given
      after 28-day rest period. A complete response (CR) was achieved in 2/91 patients.
      Moreover, 19/91 patients had a partial response (PR). Therefore, objective
      response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in
      41 patients, while the remaining 29 patients had a progressive disease (PD). OR
      rate was significantly higher in patients with a long disease-free survival than
      in patients with synchronous metastases, in nephrectomized patients than in the
      non-nephrectomized ones, and in patients with high than in those with low PS. The
      survival obtained in patients with CR or PA was significantly longer with respect
      to that found in patients with SD or PD. The toxicity was substantially low in
      all patients. This study confirms that the subcutaneous immunotherapy with IL-2
      alone is an effective and well tolerated therapy of metastatic RCC.

PMID- 9181906
TI  - [Preoperative subcutaneous immunotherapy with interleukin-2 in renal carcinoma
      with synchronous metastasis: randomized clinico-biological study. Preoperative
      use of Il-2 in renal carcinoma].
AB  - Despite the efficacy of IL-2 in the treatment of metastatic renal cell carcinoma
      (RCC), the prognosis of patients with synchronous metastases still remains poor.
      Nephrectomy itself, as well as other surgical operations, may further suppress
      the antitumor immune response. Previous studies suggested that the preoperative
      injection of IL-2 may neutralize surgery-induced lymphocytopenia in advanced
      colon cancer. On this basis, a pilot randomized study was performed in an attempt
      to evaluate the effects of a preoperative administration of IL-2 on postoperative
      lymphocyte numbers and on the survival in advanced RVV patients with more than 3
      synchronous metastases. The study included 20 consecutive patients, who were
      randomized to receive nephrectomy alone or nephrectomy plus preoperative
      subcutaneous immunotherapy with IL-2 (18 million IU/day for 3 days). Then, all
      patients underwent postoperative immunotherapy with IL-2 (6 million IU/day for 5
      days/week for 6 weeks). Surgery-induced lymphocytopenia was completely abolished
      by IL-2 preoperative injection. The frequency of postoperative complications was
      significantly higher in controls than in patients preoperatively treated with IL
      2. On the contrary, significant differences between control and patients
      preoperatively treated with IL-2 were observed neither in the clinical response
      to IL-2 immunotherapy, nor in the percent of 1-year survival. The results of this
      preliminary pilot study would suggest that IL-2 preoperative immunotherapy may
      neutralize surgery-induced lymphocytopenia and reduce the postoperative
      complications in RCC patients with synchronous metastases, without, however,
      influencing their prognosis in terms of survival time.

PMID- 9181907
TI  - [Seminal and biochemical features in a subject with male phenotype and 46, XX
      genotype].
AB  - Semen parameters and biochemical seminal markers in a 46,XX male subject were
      evaluated; Southern blot analysis with Y-DNA probes showed the absence of the SRY
      (Sex-determining Region of Y). The semen analysis, carried out three times,
      showed azoospermia, reduced volume (< 0.5 ml) and reduced pH value. Assays of the
      biochemical markers of the genital tract gave a profile very similar to that seen
      in cases of blockage of the ejaculatory ducts. This is probably due to inadequate
      differentiation of the genital tract adnexal glands leading to aplasia of the
      seminal vesicles. As a consequence, the ejaculate is formed of prostatic fluid
      only. The authors would underline the difficulties of counselling these subjects.
      This is particularly difficult where, as in this case, the genetic diagnosis is
      carried out in adulthood. In addition to the psychological stress of confirmed
      sterility, the patient must inevitably undergo the trauma of questioning his
      sexual identity.

PMID- 9181909
TI  - [Conservative surgery of epidermoid cyst of the testis].
AB  - Epidermoid cyst of the testis is a rare, benign testicular tumor. It is estimated
      that epidermoid cyst of the testis represent less than 1% of all testicular
      tumors. Opinion is divided as to the best treatment for this condition. The
      majority opinion favours excision of the tumour and preservation of the testis,
      although some recommend radical inguinal orchiectomy. We present a case of a 26
      years old man with an epidermoid cyst of the testis and submitted to organ
      preserving surgery. Organ preserving surgery with the excision or enucleation of
      the epidermoid cyst suffices, having not been reported relapse or metastasis
      after such treatment. The longest reported follow up time is 37 years. The
      conservative management of epidermoid cyst is an alternative with important
      psycho logical benefits and without jeopardizing life.

PMID- 9181908
TI  - [Therapeutic considerations on a case of mixed teratoma of the testis with
      seminomatous component].
AB  - The Authors present a case of mixed teratoma of the testis with seminomatous
      cells, occurred in a teenager. Performed the preoperative oncological staging,
      the patient was submitted to trans-inguinal left orchifunicolectomy. The presence
      of cells originated by the three embryonal layers, of stroma distributed in a
      periepithelial fashion and big cells with clear cytoplasm, permitted to formulate
      the hystological diagnosis of mixed teratoma, mature and immature, associated
      with seminomatous cells. The observation of this case offer the opportunity for
      prognostic and therapeutic considerations.

PMID- 9181910
TI  - [Metastatic linitis plastica of the bladder].
AB  - The adenocarcinoma is a rare istologic type of bladder cancer. A particular
      subset, the "signet ring cell carcinoma", can have the clinical expression of
      bladder linitis plastica. In the metastatic form this evenience is very rare and
      only two cases are reported in the literature. The Authors describe third case.

PMID- 9181912
TI  - [Comparison of free/total PSA (F/T PSA) ratio and PSA density (PSAD) in the early
      diagnosis of cancer of the prostate].
AB  - The identification of the immuno reactive molecular forms of PSA has permitted
      the identification of a correlation between Free PSA and Total PSA as the most
      important factor in the early diagnosis of prostate cancer. Cut-off of 0.15 ng/ml
      seems to be the most appropriate. The Authors consider that the use of this limit
      is important in the decision to carry out a prostate biopsy on the patients with
      PSA in the range of 4-10 ng/ml who have neither any clinical symptoms nor an
      abnormal transrectal ultrasound. In particular the sensitivity and the
      specificity of F/T PSA and the density of PSA (PSAD) have been compared at his
      limit of 0.15. In our study of 60 patients (of whom 22 were affected by cancer
      and 38 by BPH) we have noticed that 27/60 patients had a value of PSA between 4
      and 10 ng/ml and negative DRE and TRUS. On the whole the F/T PSA report showed a
      slightly higher specificity than PSAD; in contrast PSAD showed a slightly higher
      sensitivity. In conclusion, to identify the early detection of this cancer both
      tests are required as well as a biopsy.

PMID- 9181911
TI  - [ESWL for urolithiasis in a patient with transileal ureterocutaneostomy].
AB  - We present a case of urinary stone originated in the upper urinary tract and
      impacted within the ureteroileal anastomosis, in a patient with ileal conduit
      urinary diversion. Extracorporeal shock wave lithotripsy (ESWL) showed itself
      resolutive. Patients with urinary diversion have multiple risk factor for calculi
      formation (acidosis with concomitant hypercalciuria, upper urinary tract
      infections with urease producing bacteria, urostasis due to ureterointestinal
      anastomosis or ureteral narrowing), as well as predisposing conditions for stones
      to impact along the ureter or within the ureterointestinal anastomosis. Follow-up
      of these patients has to be very careful in order to avoid obliterative
      pyeloureteritis, the major complication of stone disease in patients with urinary
      conduit diversion.

PMID- 9181913
TI  - [Urinary PSA (uPSA) in the monitoring of local recurrence following radical
      prostatectomy].
AB  - The level of urinary PSA (PSAu) was measured for use as a marker in some clinical
      situations involving prostate cancer patients. Limits of physiological and
      pathological values, a quantity of which comes from the urethral glands and the
      umbilical median ligament (urachus), are still unknown. To establish the quantity
      of PSA secretion in the urethra, female PSAu was measured and found to be
      significantly low (< 0.1 ng/ml). The Authors report on 25 PR patients with
      negative margins and who had not received hormonal therapy for 30 months. The
      PSAu and the PSAs were measured on the 30th and the 60th day, and every 3 months
      thereafter in the first year and every 6 months in the second year. In 5 cases we
      observed an increase of PSAu between the 5th and 18th months. In 3 cases the PSAs
      increased 2 to 6 months later compared to the PSAu. In these 3 cases the biopsy
      indicated the presence of a localized relapse. Therefore the Authors recommend
      measuring the PSAu (cut-off 0.1 ng/ml) in the follow-up of the PR patients
      because the measurement may both identify a localized relapse earlier than the
      PSAs and indicate the localized response to hormonal or radiotherapy.

PMID- 9181914
TI  - [Surgical approach in Peyronie's disease].
AB  - The goal of surgical treatment of Induratio Penis Plastica should be the
      achievement of the best aesthetic and functional result with the lowest side
      effects. During the last two years different techniques have been proposed for
      the cases with conserved erectile function, such as Nesbit's technique, excision
      or incision of the plaque followed by implants of autologous (dermal, saphena
      vein) or heterologous (dura madre, gore-tex) patches. The criteria for the choice
      of the most appropriated surgical technique include the curvature degree, the
      plaque dimension and the penis length. In our experience 6 months after the
      surgical correction a remaining curvature was observed in 4/38 patients (10%),
      only 1 of whom needed a new surgical treatment. One case of erectile disfunction
      occurred, treated by intra-cavernous injection of PgE1.

PMID- 9181915
TI  - [Rationale for the treatment of pyelo-ureteral obstruction].
AB  - On account of the reported better results of open surgical dismembered
      pyeloplasty over the new techniques of endopyelotomy (95-100% versus 70-80%), the
      Author takes into consideration the factors which might contribute to this
      difference in results. Among these factors, the etiology of the obstruction seems
      to be of importance. In fact, while dismembered pyeloplasty involve the complete
      removal of both the anatomical and functional causes of obstruction (stenosis,
      adynamic junction), endopyelotomy should only overcome the anatomic causes of
      obstruction, most likely being inadequate in the functional causes of obstruction
      due to aperistalism of the junction. Another factor involved in the lower success
      rate of endopyelotomy is the absence of ampullar resection which may interfere
      with the recovery of a normal peristalsis. A careful and updated evaluation of
      the etiology and pathophysiology of pyeloureteral junction is therefore mandatory
      for a meaningful choice of the appropriate management and for the screening of
      patients who will benefit the most from each type of treatment.

PMID- 9181916
TI  - [Long-term follow up of patients surgically treated for pyelo-ureteral disease by
      the Anderson-Hynes technique].
AB  - A series of 48 patients with hydronephrosis (mean age 31 yrs.) underwent on
      Anderson-Hynes pyeloplasty. Assessment was carried out in 30 pts. after a mean
      observation time of 90 months, with a minimum 5 years follow-up. Clinical
      examination, laboratory investigations, renal ultrasonography, urography and
      renal scan were performed pre-operatively and at follow-up. There was one patient
      with evidence of stenosis in the ureteropelvic junction; one patient developed
      urinary leakage post-operatively and required surgical correction. All patients
      had symptoms pre-operatively and no one had symptoms post-operatively. Four
      patients had calcolosis associated, postoperatively all pts. were stone free;
      four years later one patient developed litiasis. We observed that the results of
      surgical intervention in hydronephrosis are excellent especially in patients aged
      less than 30 years.

PMID- 9181917
TI  - [Endopyelotomy: mid- and long-term follow up].
AB  - We report our experience on 24 UPJ obstruction, that underwent endopyelotomy. The
      follow-up on these patients range from 12 to 72 months. The success rate, based
      on patient symptomatology as well as urographical and scintigraphical parameters,
      was 83.3%. An adequate selection of cases, with grade of hydronephrosis and
      crossing vessels pre-operatorial detection, would possibly show a further
      improvement of success rate. The antegrade transpelvic endopyelotomy adopted in
      the most recent cases, allows the identification of crossing vessels and the
      performance of a safer endopyelotomy. The average operating time was very short,
      while morbidity was limited to 3 cases (2 of gross haematuria and 1 urosepsis).
      All this shows that endopyelotomy is the first choice treatment of UPJ
      obstruction.

PMID- 9181918
TI  - [Treatment of unusual testicular tumors].
AB  - In this work the authors make a description of the rare testis tumors. They
      underline the several histologic features and the difficulty of early diagnosis
      due to the absence of reliable markers, and as for the malignancies the unclear
      role of the radio and chemotherapy. The difference in terms of classification and
      of lack in the therapeutic standards is clear if compared with the germ cell
      tumors. These pathologies require an early surgical approach by using the
      available diagnostic imaging tools and bioptic examination.

PMID- 9181919
TI  - [Several anatomo-clinical considerations on a case of renal schwannoma].
AB  - A case of schwannoma of the parenchyma of the kidney is described. It is a
      particular case (12 cases in the literature). The nephrectomy was the therapy.

PMID- 9181921
TI  - [Post-voiding contraction: evidence and characterization in other 250 urodynamic
      studies].
AB  - We report our experience on PVC detection in 250 consecutive urodynamic
      evaluations in female patients. We emphasize the absence of evident correlations
      between the post-voiding contractions (PVCs) and their amplitude and the
      urodynamic features. We suggest a possible relation between the PVCs and two
      clinical features: enuresis (80% of cases associated with PVC) and mixed urinary
      incontinence (61.5%). Defining PVC as an improper form of detrusor instability,
      probably generated by a reduction of pelvic muscle tone, we underline the role
      performed by an urodynamic investigation defining urethral sphincter as well
      pelvic floor activity, this procedure being justified by the notorious
      interdependence between perineal and detrusorial activity.

PMID- 9181920
TI  - [Comparison of flow-cytometry and immunohistochemistry with proliferating
      monoclonal antibody. Cell nuclear antigen (PCNA) in the study of proliferative
      kinetics of renal carcinoma].
AB  - Tumor Proliferative Fraction (TPF) has been shown to correlate with prognosis in
      some malignancies. A reliable, accurate method for application in a clinical
      practice is still being sought. The aim of this study is to compare TPF as
      determined by Proliferating Cell Nuclear Antigen (PCNA) and Flow Cytometry (FC)
      in 36 consecutive patients affected by Renal Cell Carcinoma (RCC). Proliferating
      cells were identified in paraffined sections using a anti-PCNA monoclonal
      antibody (PC 10 Dako). Cell suspension for FC were prepared from fresh/frozen
      samples DNA index and S phase were evaluated using a computerized program
      (Multicycle, Phoenix). 16 samples (47.1%) were found to be aneuploid by FC (DI
      range 0.72-2.40). Aneuploid vs diploid tumors had significantly higher mean FC-S
      phase (p = 0.049) and PCNA LI (p = 0.034). Weak correlation (r-Spearman 0.416 p =
      0.01) was found between PCNA LI and grading and near to significativity between
      PCNA LI and tumor size (r = 0.335 p = 0.0061). When patients are classified
      according to nuclear grading, is evident that all PCNA G4 are aneuploid and that
      62.5% of PCNA G1 are diploid. A week correlation near to significativity is found
      between PCNA LI and S phase only in the aneuploid tumors. A more reliable
      measurement of TPF in RCC could be provided by combining the two methods. Further
      research on larger series is needed.

PMID- 9181922
TI  - [Role of alfuzosin in the treatment of functional voiding disorders in women].
AB  - Voiding dysfunction of the lower urinary tract represent a diagnostic and
      therapeutic challenge being the symptoms and urodynamic finding not strictly
      related. 34 women with urgency-frequency symptoms and post voiding residual urine
      were treated with alfuzosin 2.5 mg. twice daily alone or associated to
      oxibutinine 25 mg twice daily in patients with destrusor instability. After 30
      days from therapy 69% presented a post void residual urine less than 40 ml, while
      76% presented a flw max more than 15 ml/sec. At follow up 12 months the results
      remained unchanged. Alfuzosin alone or in association with oxibutinin can lower
      the urinary resistance to flow without modifying the maximum urethral pressure
      (MUP).

PMID- 9181923
TI  - [Endoscopic treatment of vesico-renal reflux with teflon: personal experience
      among adults and neurologic patients].
AB  - Endoscopic injection of polytetrafluoroethilene (teflon) in the vesicorenal
      reflux correction was performed for the first time in 1981 by Matouschek. Since
      1948 this method was widely employed in the clinical practices by O'Donnel and
      Puri. We present a review of our experience from march 1985 to february 1996 in
      62 normal adult and 5 neurological patients (46 female and 21 male) with
      vesicorenal reflux and who were treated by means of endoscopic correction. In
      particular, in two patients who underwent radical cystectomy for bladder tumor,
      an anatomopathological study on the tissue, were teflon was previously injected,
      was performed. In this specimens no neoplastic area was found.

PMID- 9181924
TI  - [Endoscopic treatment of vesicoureteral reflux in adults with bovine collagen].
AB  - Endoscopic subureteral collagen injection has become widely accepted a practiced
      method for the treatment of vesico-ureteral reflux in children. The aim of this
      study was to evaluate the efficacy of the treatment in adult patients affected by
      vesico-ureteral reflux. We have selected 45 patients with primary e 10 patients
      with secondary reflux (tot. 76 ureters) treated by endoscopic subureteric
      injection of collagen. The success rate after one injection in primary reflux was
      74%. 13 ureters required a 2nd or 3rd injection to achieves success. The minimum
      follow-up time for the successfully treated patients was 12 months; we did not
      observe no reflux in 92% of ureters. Endoscopic injection of collagen is a
      reliable alternative to open surgery.

PMID- 9181926
TI  - [Gene p53 mutation and prognosis in bladder tumors].
AB  - The choice of treatment for bladder tumors is based on pathological criteria,
      i.e. staging and grading mainly. It has recently been observed that genetic
      alterations that involve activation of oncogenes and inactivation of suppressor
      genes can occur during tumorigenesis. p53 protein is coded for by a genes on
      chromosome 17, and is able to suppress malignant transformation and
      proliferation; it can be important in maintaining the integrity of DNA, when
      damaged during neoplastic disease. We have analyzed samples of transitional cell
      carcinoma of the bladder of 60 patients managed by conservative treatment; all
      the specimens have been stained for p53 protein. We could observe that the
      presence of the protein p53 is correlated with staging and grading and is
      associated with an increased risk of relapse and progression. Patients with
      transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53
      reactivity should be considered for protocols of adjuvant treatment.

PMID- 9181925
TI  - [The use of type A botulin toxin in the treatment of detrusor-sphincter
      dyssynergia].
AB  - The detrusor-sphincter dyssynergia (DSD) is a common and significant problem for
      patients with spinal cord lesions. If not treated, DSD can lead to severe and
      potentially lethal complications (urinary tract infections and renal damage). BTX
      inhibits acetylcholine release at the neuromuscular junction, producing muscle
      chemical denervation in the site of injection. The aim of this preliminary study
      was to test the safety and the effects of BTX injection in the spastic urethral
      rhabdosphincter in patients with DSD. Five patients (3 M, 2 F; mean age 43 years,
      range 22-56) with DSD entered the study. Videourodynamic parameters were
      controlled before BTX injection at 10 days, at 3 and 6 months after infiltration.
      The aim of this preliminary study was to test the safety and the effects of BTX
      injection in the spastic urethral rhabdosphincter in patients with DSD. The post
      void residual urine volume, the maximum pressure of emptying and the maximum
      pressure of urethral closure are reported in Tab. II-III-IV. Patients reported
      subjective improvement of bladder emptying and improved quality of life. No
      adverse effects related to pharmacological activity of BTX or to infiltration
      procedures were observed.

PMID- 9181927
TI  - [Levels of monokines in peripheral monocytes in patients with superficial tumors
      of the bladder treated with BCG. Results after 1- and 3-year follow-up].
AB  - BCG has been shown in prospective randomized clinical trials to provide superior
      therapeutic results when composed to transurethral resection alone, or to
      adjuvant therapy with Thiotepa or Adriamicin. Even if the mechanism by which BCG
      mediate antitumor activity are not clearly established, an association between
      the immunological response and antitumoral activity is known IL-1 and TNF alfa
      are the monokines that have multiple biological effects, including linfocyte
      proliferation, production of fever, augmentation of cytotoxicity and production
      of cytokines. The goal of this study is show the response from LPS induced and
      not peripheral monocytes of superficial bladder cancer patients BCG treated and
      not, i.e. the levels of TNF alfa, IL-1 and not IL-6.

PMID- 9181928
TI  - [Role of MCP-1 chemokine in the response of monocytes of patients with
      superficial tumors of the bladder treated with BCG immunotherapy].
AB  - Mechanism by which intravesical BCG treatment mediates antitumor activity are
      currently poorly understood. We initiated studies to determine the sequence and
      the factors that produce the immunological events. During the inflammatory answer
      a lot of molecules are produced. Chemokines MCP-1 and RANTES induces the mast
      cell recruitment, that begins the "immunological fall". In our study 5 patients
      with superficial bladder cancer treated with BCG present an improvement of this
      cytokines correlated with a tumor-free status.

PMID- 9181929
TI  - [Transurethral incision of the prostate].
AB  - In this paper the Authors present the preliminary results of an investigation of
      a series of a patients with BPH who have undergone TUIP by modified monolateral
      incision. Post-operative complications, hospital stay and short-term urine flow
      values have been assessed. From June '94 to April '96 at the Department of
      Urology of the Hospital of Matera, 56 patients with BPH-induced cervico-urethral
      obstruction undergone TUIP. Their average age was 66; the average follow up was
      9.5 months. Thirty-one of them ha bladder catheters. The patients were selected
      by ultrasonographically measured prostatic volume (< or = 30 gr). The operation
      was almost in all cases conducted under spinal anaesthesia. A 5-10 mm-long
      monolateral incision was made medial to the right urinary meatus, starting just
      behind the trigonal bar and going up to the pre-spyncteric region, laterally to
      the veru montanum. The incision was made up to the section of the muscle fibres
      of the trigone and those of the prostate capsule, exposing the fat. Post
      operative assessment included a urine culture after 15 days as well as a urine
      flow measurement every three months. The operative took an average of 10.3
      minutes. The catheter was removed on average after 2 days. Post-operative
      hospitalization lasted on average 3.9 days. No post-operative complications were
      encountered. Only in 3 cases in which a catheter with no Coude tip was used, was
      it difficult to insert. In no case was a blood transfusion necessary. Six
      patients with normal pre-operative sexual activity maintained their normal
      ejaculation. Of the 29 patients that had got through the 3-months' follow-up,
      seven who had been catheterized before the operation, showed, along with an
      average volume of urine of 236.7 cc, a maximum flow value of 10.8 ml/sec., an
      average flow of 6.8 ml/sec. and a bladder emptying time of 36.8 sec. The other 22
      patients had an average maximum flow speed of 20.5 ml/sec. (+121.5%), an average
      flow of 10.3 (123.9%), an emptying time of 33 sec. (-8.8%) with an average volume
      of urine of approximately 300 cc (+58.9%). Thus, in view of the noteworthy post
      operative improvement in the symptomatology, both in subjective and objective
      terms, as well as the low rate of complications and the considerably reduced
      costs, TUIP may be considered a valid surgical alternative for treatment of BPH
      with adenomas weighing < or = 30 gramis in selected patients.

PMID- 9181930
TI  - [Proposal of a new transurethral method for repeated prostatic biopsy].
AB  - In many clinical situations a patient affected by pre-cancerous prostatic
      lesions, suspected cancer or true cancer (assessed through biopsies or
      incidentally) must undergo iterative bioptic examinations. Three groups can be
      sub-divided: A) Patients with no previous endoscopic resection. B) Patients with
      previous endoscopic resection for BPH. C) Patients with previous RP for cancer. A
      persistent clinical suspicion for high PSA, a bioptic assessment for Ca T1c or
      PIN belong to the first group. A suspected cancer in a patient who had already
      undergone TUR, or a T1a neoplasia assessed incidentally, or PIN found in the
      resected fragments constitute the second group. A suspected local relapse after a
      RP characterizes the third group. In 28 cases of these clinical diagnoses, we
      have applied a new method of bioptic trans-urethral sampling. We used an eco
      reflectant, flexible needle and applied it under endoscopic vision to the
      transitional zone or to tissues of the already resected prostatic fossa. In the
      first case these biopsies were integrative of the usual randomized biopsies. If
      transrectal ultrasound had given evidence of altered structures, biopsy was
      carried out with selective ultrasound guided technique. This procedure has proved
      to be minimally invasive, easy to carry out and particularly adapted to bioptise
      zones that are easier to reach transurethrally or tissues with low thickness.

PMID- 9181931
TI  - [Radiologic staging after surgical, chemical, and radiation treatment of non
      seminomatous tumors of the testis].
AB  - The aim of this work was to evaluate the clinic usefulness of Computed Tomography
      (CT) and Magnetic Resonance (RM) in the staging after surgery, radiotherapy and
      chemotherapy of the nonseminomatous germ cells tumours of the testis. The Authors
      discussed the CT and MR dimensional criteria for the diagnosis of retroperitoneal
      metastases of the nonseminomatous germ cells tumours and delineated their CT and
      MR morphologic appearances in detail. The density of the residual mass on CT was
      classified as solid, cystic and half-cystic. The retroperitoneal hematoma and
      lymphocele formed as a complication respectively of orchiectomy and
      retroperitoneal lymphadenectomy can be misinterpreted to represent metastatic
      disease on post operative staging CT scans. Early recognition of this
      complication are crucial if unnecessary treatment is to be avoided. Finally the
      Authors evaluated, in patients affected from nonseminomatous germ cells tumours
      of the testis, the possibility to characterize with CT and MR imaging the
      retroperitoneal mass. The density and character of the residual mass on CT scan
      did not reliably predict the histology. On the basis of tumor consistency and
      signal intensity in T1 and T2 weighted images, MR cannot yet warrant any
      conclusion about the ultimate effect of chemotherapy.

PMID- 9181932
TI  - [Diagnostic efficacy of free SPA/total PSA ratio in the diagnosis of prostatic
      carcinoma].
AB  - Prostate specific antigen, specific organ and tissue marker, is a glycoprotein
      present in serum in different molecular forms, i.e. not protein bound and bound
      to proteins (PSA-ACT and PSA-AMG). The total PSA is expressed by the sum of the
      non protein bound value (free-PSA) and PSA-ACT. The aim of our study was to
      evaluate the hypothesis that measurement of free/total PSA ratio may be helpful
      in the differential diagnosis of prostatic pathology. Our study was conducted on
      350 patients, to whom the total-PSA, free-PSA and f/t PSA had been performed; 250
      patients showed a total PSA between 2.5 and 10 ng/ml and 185 of them had symptoms
      of bladder out-flow obstruction. In all of the 250 patients digital rectal
      examination, transrectal ultrasound and prostatic biopsy were performed. 100
      patients were controls. The cut-off to differentiate between benign and malignant
      prostatic disease was 16%. The pathologic diagnosis was related to the f/t PSA
      ratio, and in particular those patients with a f/t PSA lower than 16% were
      expected to be prostatic carcinoma, while those with a f/t PSA higher than 16%
      were expected to be benign prostatic hypertrophy. The diagnostic accuracy of the
      ratio was calculated, and it was observed that it was 88.65% in the diagnosis of
      benign prostatic hypertrophy, while in the diagnosis of prostatic carcinoma it
      was 84.5%. We can therefore assume that f/t PSA can add useful information on
      prostatic pathology, eventually sparing unnecessary prostatic biopsies.

PMID- 9181933
TI  - [Half-life of blood PSA after radical prostatectomy. Correlations with
      pathological stage and clinical course of the disease].
AB  - PSA half-life was calculated in 37 patients after radical prostatectomy to
      identify earlier patients with residual disease. The half-life calculated in
      patients potentially "cured" with absolute PSA values inferior to 0.5 ng/ml after
      28 days, was significantly different (P = 0.0008) from the group of patients
      "uncured" (PSA > 1.0 ng/ml) and from those ones that, despite of detectable PSA
      level, had evidence of recurrence in the following follow-up. In comparison with
      the absolute value, the PSA half-life is able to define in the group of patients
      potentially "cured" those who could have a recurrence in the future.

PMID- 9181934
TI  - [The effect of electrostimulation of the hypothalamic mamillary nuclei on the
      vascular permeability of the skin in intact and capsaicin-pretreated rats].
AB  - Electrical stimulation of the hypothalamic mamillary nuclei increased the
      permeability of the skin blood vessels in rats. Pretreatment of the animals with
      capsaicin prevented the effect. The mamillary nuclei seem to take part in the
      central mechanisms of efferent function of the capsaicin-sensitive neurons.

PMID- 9181935
TI  - [Hydrolases of the digestive and nondigestive organs in rhesus macaque monkeys].
AB  - Distribution of activity of a wide range of hydrolases was characterised in the
      duodenum, ileum, jejunum, and colon, as well as in the liver, kidney and spleen
      in Macaca rhesus. The findings suggest presence of a complex enzyme system
      performing the membrane and intracellular hydrolysis of nutritional substances,
      in the small intestine of the primates as well as other mammals. This system,
      along with the hydrolases of the colon and non-digestive organs, seems to
      function as an enzymatic barrier.

PMID- 9181936
TI  - [At the head of 2 Russian university physiology departments (Filipp Vasil'evich
      Ovsiannikov)].

PMID- 9181938
TI  - [The effect of naloxone and leu-enkephalin on the atretic changes in the ovarian
      follicles of hypophysectomized rats].
AB  - In 21--23-day-old female Wistar rats with atresia of the ovarian follicles,
      naloxone administration increased the number of 100-200 mcm follicles with
      atresia-induced changes, whereas enkephaline prevented the effect. Role of the
      brain opioid system in the above phenomenon, is discussed.

PMID- 9181937
TI  - [The effect of chronic social conflicts on the indices of nonspecific resistance
      in mice].
AB  - Male mice C57BL/6J were divided into victors and losers in daily confrontations.
      After 10 confrontations, the losers developed a leukopenia, a decrease in the
      Thymus index, protein concentration and immunoglobulins class G, as well as a
      decrease in the agglutinins titres to the ram erythrocytes in the blood plasma.
      The same changes occurred to a minimal extent in the victors. The changes seem to
      reflect a stress sensitivity degree.

PMID- 9181939
TI  - [The asymmetry of the intrinsic connections of the cat striate cortex in the
      projection zone of the central visual field].
AB  - Spatial distribution of intrinsic connections in the visual field centre
      projection zone of the cat striate cortex, was investigated. Retrogradely
      labelled cells formed an oblong area and were found in superficial as well as
      deep cortical layers. The labelled cells were located mostly medially to the
      column under study. The revealed asymmetry shows that the orientation column
      cells have more extended connections with cells representing the visual field
      periphery. We suppose that the "silent" regions are asymmetrically located in
      respect to the orientation column cells' receptive fields. This can account for
      the influence of the visual field periphery.

PMID- 9181940
TI  - [The morphophysiological restructuring of the sensory bushy receptor of the frog
      bladder under the influence of colchicine].
AB  - Colchicine was shown to decrease the afferent spontaneous unit activity frequency
      as well as the number of small terminal receptor plates (< 5 mu) increasing,
      however, the number of large ones (10-25 mu) in frogs. Colchicine seems to act on
      neurolemma rather than on cytoplasmic microtubules.

PMID- 9181941
TI  - [The significance of motor activity in regulating the cholinergic sensitivity of
      cat muscle spindles].
AB  - Following a complete transection of the spinal cord at the Th12-L1, an augmented
      chemosensitivity of the nuclear bag and nuclear chain fibres was observed. The
      supersensitivity of the intrafusal fibres to subecholine was higher than to
      acetylcholine. The supersensitivity of the intrafusal muscle fibres against the
      background of intact anatomical projections suggests that the motor activity
      rather than axonal transport plays the leading role in regulation of the
      cholinergic sensitivity of intrafusal muscle fibres.

PMID- 9181942
TI  - [Disturbances of the normal structuring of the blood flow in the microvessels as
      the cause of hemorheological disorders].

PMID- 9181943
TI  - [The possible mechanism of the noradrenaline enhancement of the arterial
      baroreceptor reflex].
AB  - In anaesthetized cats intravenous infusion of norepinephrine induced the increase
      in arterial pressure and suppression of renal nerve electrical activity. The
      latter followed the infusion was stopped and arterial pressure returned toward
      control. The baroreflex suppression of sympathetic activity associated with
      norepinephrine increased in the case of preliminary mechanical damage to blood
      brain barrier. Duration and intensity of the sympathetic activity suppression
      following norepinephrine infusion depended on the magnitude of hypertensive
      reaction and the rate of elevating in arterial pressure under the action of
      norepinephrine. Norepinephrine at the similar concentrations did not depress
      sympathetic activity if the arterial pressure was stabilized on the resting
      level. These data support the supposition that the elevation of arterial pressure
      due to norepinephrine infusion increases the ability of catecholamine to enter
      brain and in this way activates the central limb of arterial baroreceptor reflex.

PMID- 9181944
TI  - [The limitation of acute hypotension and hyperactivation of the vascular
      endothelium in rats with an experimental myocardial infarct by using preliminary
      adaptation to physical load].
AB  - Adaptation to swimming exercise was shown to increase the endothelium-dependent
      relaxation of the rat aorta, leaving the BP unaffected. In experimental
      myocardial infarction, the adaptation limited the BP fall and completely
      prevented an excessive suppression of norepinephrine-induced contractions of the
      aorta. An adaptation to exercise seems to be an efficient protective factor in
      pathological conditions involving the NO overproduction and endothelial
      hyperactivation.

PMID- 9181945
TI  - [Agonistic behavior during stress inhibits the development of learned
      helplessness in rats].
AB  - Male Wistar rats were exposed to inescapable shock in individual chambers (IS),
      or shocked in pairs (PIS). The latter rats were fighting during the shock
      administration. In 48 hrs, all the rats were subjected to escape/avoidance task
      in a shuttle-box. Failures increased significantly in the IS rats as compared
      with the PIS and intact rats. Dexamethasone administration decreased the plasma
      corticosterone level in the latter groups, but not in the IS rats. The findings
      suggest that an inescapable shock induces no learned helplessness in rats having
      an opportunity of agonistic interaction during the shock. The findings suggest
      also a stress-protective effect of agonistic contacts under averse conditions.

PMID- 9181946
TI  - [The distribution of cardiac output in waking rats with a decrease in body
      temperature to 2.3 degrees C through cooling or hypoxia].
AB  - Heart output distribution (HO) was characterised by incorporation of 15-micron
      131-I [correction of 15- 131J]-albumin microspheres after cooling and altitude
      hypoxia in alert rats. There was no significant change in the HO distribution in
      experimental rats except a 1.5-fold increase of the skin HO portion and a 1.5
      fold decrease of the bone marrow HO portion in hypothermic rats. The latter
      developed an increase in the blood flow in skeletal muscles and different skin
      parts as compared with the hypoxic rats.

PMID- 9181947
TI  - [To what extent is cardiac work capacity preserved after long periods of clinical
      death under hypothermia?].
AB  - After the heart arrest during 1-4 hrs in immersion hypothermia (water temperature
      9 degrees C), heart beats were restored. The mechanical power of the heart,
      however; was reduced to 64-73% of the initial level in 1-3 hrs and to 39% in 4
      hrs after the cardiac arrest.

PMID- 9181948
TI  - [A physiological analysis of kidney ion-regulating function in children with
      enuresis].
AB  - Peculiarities of the excretion of ions (Na, K, Ca, Mg) and water were studied in
      healthy children and children with the nocturnal enuresis, aged 6-15 years. A
      greater diuresis in the enuretic children is due to an increased excretion of the
      osmotically active substances including Na and Mg; excretion of K and Ca does nor
      differ from the control. A new formula is proposed for the quantitative
      evaluation of the role of different substances in the osmolar clearance. A high
      correlation is found between the sodium and magnesium excretion and the osmotic
      free water reabsorption. A single intranasal administration of 1-deamino-8-D
      arginine-vasopressin (DDAVP) to the children before their going to bed returned
      to the norm the sodium and magnesium excretion in the enuretic children. It is
      suggested that the defect peculiar to this particular pathology is associated
      with a decrease in the ion reabsorption in the thick ascending Henle loop. The
      normal level of the ion transport is restored after stimulation of V2-receptors
      by DDAVP. An explanation is suggested of the mechanism of the increase of
      diuresis with a simultaneous rise in the osmotically free water reabsorption in
      children with enuresis.

PMID- 9181949
TI  - [Conflict of motivations and the reaction of neutrophilic granulocytes in rats].
AB  - A motivational conflict induced a decrease in the cation proteins content in
      neutrophils within 12 hrs after the stress in make rats. Activity of enzymes
      taking part in the respiration did not change. A cyclic variation of the cation
      proteins content was found during the oestrus cycle in neutrophils of female
      rats.

PMID- 9181950
TI  - [The effect of preliminary acute hypothermia on the temperature-regulating
      activity of the motor units in rat skeletal muscle].

PMID- 9181951
TI  - [The effect of gamma radiation at low doses on the receptor binding of
      triiodothyronine in the nuclei of rat liver cells].

PMID- 9181952
TI  - [Ornithine decarboxylase in the organs of rats under chronic exposure to gamma
      radiation at a low dosage rate].
AB  - Chronic exposure of rats to gamma-irradiation at the dose rates of 1.1, 2.1, and
      12.9 cGy/d in the dose ranges of 9-165, 17-315, and 100-2000 cGy, respectively,
      modified the ornithine decarboxylase (ODC) activity in the radiosensitive
      (thymus, spleen) and radioresistant (lung) organs. A nonmonotonic dependence of
      the ODC activity on the cumulative radiation doses was observed: a decrease in
      the ODC activity caused by low cumulative radiation doses (after 8 days of
      exposure) gave way to the level that was close to the control (after 45 and 90
      days); after 150 days of exposure, the activity of ODC increased in some organs
      (spleen and lung). It was suggested that this nonmonotonicity has its origins in
      the radiation triggering the regulatory systems of the cell homeostasis.

PMID- 9181953
TI  - [Changes in the intensity of lipid peroxidation in the blood plasma of sheep
      under repeat gamma irradiation after chronic gamma exposure].
AB  - The indices of lipid peroxidation and the contents of alpha-tocopherol and
      retinol in the blood plasma of sheep exposed to repeated gamma irradiations were
      studied. It was shown that a repeated acute gamma irradiation of sheep with
      sublethal and lethal doses after 9 months of chronic low-dose gamma irradiation
      adversely affected the activity of the lipid free-radical oxidation. A radiologic
      pathology in the repeatedly irradiated animals developed as a decrease in the
      intensity of spontaneous chemiluminescence. Also, a tendency to an increase in
      the concentration of malonic dialdehyde was observed along with weak changes in
      the contents of triene and diene conjugates and the levels of alpha-tocopherol
      and retinol.

PMID- 9181954
TI  - [Changes in the content of ribonucleic acid in the blood cells and plasma
      compared to the hematological indicators of a radiation-induced lesion in rats].
AB  - A whole-body gamma irradiation of rats with a dose of 8.5 Gy caused a significant
      decrease in the RNA concentration in the blood. The original level of
      concentration was restored within 3 weeks after irradiation and exceeded by the
      21st day after irradiation. The changes were studied in terms of the
      haematological indices of a radiation-induced damage.

PMID- 9181955
TI  - [Gutron studied as an agent for preventing radiation lesions].
AB  - Experimentally, with the use of mathematical modeling, a radioprotective effect
      and optimum usage of alpha-adrenomimetic Gutron was shown on CBA male-mice
      exposed to radiation. Injections of 1 to 5 mg/kg Gutron to the mice 10 to 40 min
      and 1 to 4 h before the irradiation with the doses of 6 to 7.5 Gy ensured the
      survival rates of the exposed animals with the protection coefficient s of 0.6 to
      0.7 and 0.4, respectively.

PMID- 9181956
TI  - [The characteristics of the development of endogenous intoxication after chronic
      radiation exposure and thermal trauma].
AB  - Chronic whole-body gamma irradiation of rats at the cumulative doses of 0.25 or 1
      Gy results in a significant increase in the bacterial toxemia. A thermal injury
      suffered 3 months after the irradiation aggravates the bacterial toxemia and
      increases a number of medium-mass molecules. A thermal injury alone causes less
      pronounced changes in the toxemia indices as compared to the above combined
      damage.

PMID- 9181957
TI  - [Indometofen causes biochemical changes in the blood cells characteristic for a
      radioresistant state of the body].
AB  - The DNA and RNA contents, RNA/DNA ratio, and spontaneous and latex-induced
      oxidant activity indices of the whole blood were studied in the nitroblue
      tetrazolium test of mono- and polymorphonuclear blood leucocytes of intact dogs
      after injection of lipopolysaccharide pyrogenal. Significant changes in the above
      parameters were revealed for radioresistant (survived) and radiosensitive (lost)
      animals exposed to a subsequent prolonged gamma irradiation with a lethal dose of
      7.64 Gy (LD75/45). Peroral introduction of 30 mg/kg indometofen (an indole analog
      of tamoxifen), which is a potential radioprotector, to dogs increased the
      survival rates of the irradiated dogs up to 93% and aided in the adaptive
      biochemical changes in the nuclear cell compartment of blood to induce a
      radioresistant status of the organism.

PMID- 9181958
TI  - [An interleukin-1 beta efficacy study in the treatment of combined radiation
      thermal lesions].
AB  - The experiments were carried out on F1 (CBA x C57B16) male-mice. It was shown
      that, in contrast to a therapeutic effect of IL-1 for the solely irradiated mice,
      a single subcutaneous injection of 100 micrograms/kg recombinant human IL-1 beta
      in 4 h after a combined radiation-thermal injury (CRTI) increased significantly
      the death rate of the animals within the first 2-4 days. Administration of 150 ng
      IL-1 per mouse in 4, 24, or 48 h after the CRTI decreased an average life-span of
      mice. A single injection of cytokine in 5 days after the CRTI increased the
      survival rate by 45%. Repeated injections IL-1 with a dose of 100 pg per mouse in
      2, 4, and 6 days after the CRTI did not aid in the haematological indices and did
      not affect the survival rate of the animals.

PMID- 9181959
TI  - [Changes in the hematopoietic system and in the concentrations of blood
      regulatory cytokines after acute irradiation and a combined radiation-thermal
      lesion].
AB  - Acute radiation and combined radiation-thermal injuries (CRTIs) were modelled in
      the experiments on CBA x C57B16 mice. Changes in the concentrations of endogenic
      and lipopolysaccharide-induced TNF-alpha in the blood serum were measured in 3 to
      24 h after gamma-irradiation at a dose of 7 Gy and a combined radiation-thermal
      injury. The status of mature and reserve pools of the bone marrow granulocytes
      was determined from the reaction of leukocytes mobilization to blood in response
      to the administration of interleukin-1 beta (IL-1 beta) in 48 h after Irradiation
      and CRTI. The contents of IL-3 and IL-6 in the blood serum, the level of cytokine
      secretion by the bone marrow cells were determined in vitro in the peak phases of
      acute radiation and combined injuries. No significant changes in the reaction of
      the bone marrow cells and in the level of pancytopenia were revealed after acute
      radiation and CRTIs, which could help in understanding an increase in the death
      rates after CRTIs. Also, quantitative changes in the TNF and IL-6 concentrations
      in the blood serum were estimated along with those in the level of secretion of
      IL-3 by the bone marrow cells of mice exposed to radiation and CRTIs.

PMID- 9181960
TI  - [The behavior of inulin in aqueous solutions under exposure to gamma radiation].
AB  - Radiochemical transformations of inulin in aqueous solutions, in air, in the
      presence of inert gases, helium, nitrogen, and in nitrous oxide exposed to
      various doses of 60Co gamma irradiation were investigated. It was shown that
      interactions of inulin with OH radicals are principally responsible for
      radiolytic decomposition of inulin. The data on radiolysis of more simple model
      systems were used to make available decomposition of absorption spectra of gamma
      irradiated aerated aqueous solution of inulin.

PMID- 9181961
TI  - [The diverse effects of the combined action of cadmium chloride and ionizing
      radiation on the content of metallothioneins in mouse bone marrow and liver].
AB  - It was shown that introduction of cadmium chloride (0.75 mg/kg Cd2+) in
      combination with gamma irradiation (8.5 Gy) of mice increases the level of
      metallothioneines (MTs) in the bone marrow and liver of mice. The maximum effect
      was observed in 24-30 h after the performance. Similarly, irradiation with the
      doses of 3 to 10 Gy resulted in an increase in the contents of both MT isoforms
      (MT1 and MT2) in the bone marrow in 24 h. A combined action of gamma irradiation
      and a heavy metal caused an additive effect on the MT content in the bone marrow,
      whereas the MT content in liver was 2 times lower than that predicted
      theoretically. A possible mechanism of the discovered phenomenon was discussed.
      Supposedly, it is associated with different degrees of the radiation-induced
      inhibition of the MT1 and MT2 expression by cadmium ions.

PMID- 9181962
TI  - [The effect of multiple combined external exposure to gamma radiation and the
      administration of 241Am on the body of the rat].
AB  - Biological effects of multiple gamma irradiation combined with incorporated 241Am
      were studied. A cumulative effect provided by each agent was estimated. The
      radiation disease development was more serious than that caused by a separate
      action of each radiation agents in the same doses.

PMID- 9181963
TI  - [The appearance of a fracture of radioresistant cells in a fibroblast population
      irradiated at high doses].
AB  - Two sublines of Djungarian DEF 4/21 hamster cells survived after gamma
      irradiation with the doses of 10 and 20 Gy were obtained. The survived cell
      posterity (SCP) of both cell lines are considerably more clonogenic. They show a
      higher proliferative activity and a shorter period of generation than the control
      cells. The sublines are several times more radioresistant as compared to the
      original cells. After exposure to high doses of radiation, the cell culture of
      the SCP exhibits a 17 to 20% high-resistant fraction. Supposedly, the cells of
      this fraction are responsible for repopulation after exposure to lethal doses of
      gamma irradiation.

PMID- 9181964
TI  - [The lethal and mutagenic actions of radiations with different LETs on mammalian
      cells].
AB  - Inactivation and induction of mutations in the HGPRT locus in Chinese hamster
      cells after irradiation with accelerated heavy ions in the LET range of 20 to 367
      keV/micron were studied. In both cases, inactivation and induction of mutations,
      the LET dependence of RBE is described by a curve with a local maximum in the
      range of 80 to 100 keV/micron. The maximum RBE value for the mutagenic action is
      almost twice as high as that for inactivation. However, the RBE coefficients of
      the mutation induction criterion for a certain level of cell-survival is lower
      significantly and tend to decrease with an increase in inactivation. The obtained
      data show that the mutagenic effects, induction of chromosome aberrations, and
      deaths have their origins in the same kind of primary damages, i.e., double
      strand breaks of DNA.

PMID- 9181965
TI  - [Increased plasma membrane permeability for Ca2+ in radiation-induced thymocyte
      apoptosis].
AB  - Parameters of the Ca2+ permeability (the 45Ca influx rate in the presence of
      orthovanadate blocking the Ca(2+)-ATPhase, and the initial rate of the 45Ca
      uptake) and the DNA fragmentation were determined in rat thymocytes after gamma
      irradiation-induced (with a dose of 5 Gy) apoptosis. Within the first 30-90 min
      after irradiation, the 45Ca influx rate that is characteristic of the membrane
      passive permeability remained unchanged. The initial rate of the 45Ca uptake that
      is characteristic of the Ca2+ exchange almost doubled. In 90-180 min, the rate of
      the 45Ca influx in the irradiated cells increased 1.5 to 2.0 times. An increase
      in the DNA fragmentation was observed in 90-120 min after irradiation of
      thymocytes; in 3 h, it developed up to 50%. Thus, modification of the membrane
      Ca2+ permeability in the irradiated thymocytes precedes a stage of initiation of
      the DNA degradation. A degree of disturbance of the membrane passive permeability
      increases as the thymocyte apoptosis progresses. The obtained data suggest that
      disturbance of the passive Ca2+ permeability and the intracellular Ca2+
      homeostasis are responsible for the apoptosis of lethally irradiated thymocytes.

PMID- 9181966
TI  - [The immunocorrection with Aerosil-350 of the natural resistance of mice found
      under conditions of an elevated radiation background].
AB  - Experiments on the CBA mice that had been within 30 km of the Chernobyl NPP
      accident for 3 months revealed a decrease in the phagocytic and bactericidal
      properties of peritoneal macrophages accompanied with a disturbance in the
      production of interleukin-1 and a tumor necrosis factor responsible for the cell
      immunity. A single administration of a silicon-containing enterosorbent Aerosil
      350 expedient to remove radionuclides and ensure the organism detoxication made
      it possible to correct and restore the affected cell and organism immunity for 7
      days.

PMID- 9181967
TI  - [The dependence of the frequency of stable and unstable chromosome aberrations on
      the dose of the irradiation of human lymphocytes in vitro].
AB  - Two methods (FISH and Giemsa) were used to estimate the frequency of stable and
      unstable chromosome aberrations in human lymphocytes exposed to gamma-irradiation
      in vitro in the dose range of 0.1 to 1.5 Gy. The DNA-probes specific to the
      chromosomes 1, 4, and 12 were used in combination with a pancentromeric probe. It
      was revealed that the dose-effect dependences for translocations (FISH) and
      dicentrics (FISH and Giemsa) were similar and could be adequately described by a
      linear-quadratic function.

PMID- 9181968
TI  - [The approximation of cell distribution by the number of aberrations in the
      fractionated gamma-neutron irradiation of a human lymphocyte culture at the
      presynthesis stage (the G0 and G1 stages of the cycle) based on a theoretical
      model].
AB  - A theoretical model is suggested that allows calculating a yield of cells with a
      number of aberrations caused by fractionated gamma irradiation using the
      corresponding data for a separate irradiation. The value of a cytogenetic
      interaction of damages induced by two fractions of irradiation doses was used as
      a free parameter of the model. In terms of the model, approximation of
      experimental functions of the cell distribution in a number of exchange
      aberrations caused by gamma and/or neutron irradiation was made. At a stage G0,
      with the 1 h interval between the dose fractions, approximation was successful
      only for irradiation with equal or isoeffective dose fractions; with the interval
      of 5 h, it was successful for all types of irradiation except for two highest
      doses of fractionated neutron and gamma/neutron irradiation. At a stage G1,
      approximation was satisfactory almost for all types of fractionated gamma/neutron
      irradiation irrespective of the interval between the dose fractions and of a dose
      of fractionated gamma irradiation with the interval 1 h. For the fractionated
      neutron and neutron/gamma irradiation at a stage G1, approximation of
      experimental distributions was unsatisfactory in all the cases.

PMID- 9181969
TI  - [Quantitative patterns in the yield of chromosome aberrations in a human
      lymphocyte culture with fractionated gamma-neutron irradiation at different
      stages of the mitotic cycle. The cytogenetic effects at stage G1].
AB  - Quantitative regularities of the chromosome aberrations yield in the human
      lymphocyte culture affected by fractionated gamma/neutron irradiation (in the
      direct and inverse sequences) at a stage of the presynthesis (G1), with the 1 to
      5 h intervals between the dose fractions, were studied. The obtained results were
      compared with those for the stage G0 described in the previous paper. The
      cytogenetic effect, with doses and intervals between the dose fractions being
      equal, depended significantly on a stage of the mitotic cycle of the cells. The
      effect was opposite for the stages G0 and G1: super- and subadditive,
      respectively.

PMID- 9181970
TI  - [Quantitative patterns in the yield of chromosome aberrations in a human
      lymphocyte culture with fractionated gamma-neutron irradiation at different
      stages of the mitotic cycle. The cytogenetic effects at stage S].
AB  - Quantitative regularities of the chromosome aberrations yield in the human
      lymphocyte culture affected by fractionated gamma/neutron irradiation (in the
      direct and inverse sequences) at a stage of the replicative DNA synthesis (S),
      with the 1 to 5 h intervals between the dose fractions, were studied. The
      obtained results on the cytogenetic effect of interaction of damages were
      compared with those for the stages G0 and G1. In contrast to the latter cases,
      where occurrence of superadditive effects was high, only subadditive effects were
      observed for the stage S.

PMID- 9181971
TI  - [An estimation of the half-life periods of 137Cs content in the root-inhabited
      soil layer of meadow ecosystems].
AB  - A model of vertical migration of 137Cs was developed with taking into account the
      sorption of this radionuclide by soil. The parameters of the model and prediction
      of vertical distribution of radionuclides in soils are estimated for a wide range
      of meadows and soils, typical of various regions of Russia contaminated after the
      accident at the Chernobyl NPP. Ecological half-lives of the 137Cs content in the
      root-containing zone of soil were calculated. It was shown that a contribution of
      self-purification of soils into an overall decrease in the 137Cs content in the
      root-containing zone (0-10 cm) varies from 2.2% for sandy loam soils (dry
      meadows) to 99% for peaty soils (peat-bog meadows).

PMID- 9181972
TI  - Novel methods for identification and quantification of the mushroom nephrotoxin
      orellanine. Thin-layer chromatography and electrophoresis screening of mushrooms
      with electron spin resonance determination of the toxin.
AB  - Orellanine, (2,2'-bipyridine)-3,3',4,4'-tetrol-1,1'-dioxide, the toxin from
      several Cortinariace species, induces an acute renal failure which can be very
      severe or even irreversible and fatal. It is therefore important to be able to
      quickly and simply identify orellanine in mushroom samples with classical
      methods, readily available in any laboratory, such as anti-poison centers. This
      article reports the results of three analytical methods: classical TLC on
      cellulose plates in n-butanol--acetic acid--water and two original methods,
      electrophoresis on agarose gel and direct electron spin resonance (ESR) after
      enzymatic oxidation. They were applied to detect orellanine in 34 Cortinariaceae
      and 4 other species of toadstools. Our three sets of results are convergent. TLC
      (detection limit: 15 ng with fluorescence densitometry), electrophoresis (25 ng)
      and even ESR (5 micrograms), are sensitive enough for our purpose, and a
      sophisticated method like HPLC (detection limit: 50 pg) is not required. As the
      ESR spectrum of the toxin semiquinone is highly specific, TLC or electrophoresis
      coupled with ESR are a convenient alternative to liquid chromatography coupled
      with mass spectrometry, with the same specificity, for a confirmation or with
      samples such as ours with high toxin contents. ESR unambiguously confirms the
      relatively high contents of orellanine, from 0.45% (C. henrici) to 1.1-1.4% (C.
      orellanus), found in five Cortinarius from the subgenus Leprocybe, section
      Orellani. The five species, though they are from different geographic origins,
      have a more or less common pattern of fluorescent compounds, among which
      orellinine and orelline beside orellanine. It can be useful to note that
      orellanine semiquinone can be easily detected by ESR directly in the fresh
      mushroom. The toxin is absent in the other mushrooms we tested, especially in D.
      cinnamomea and C. splendens, which have been claimed as toxic and suspected to
      contain orellanine.

PMID- 9181973
TI  - Modification of polystyrenic matrices for the purification of proteins. Effect of
      the adsorption of poly(vinyl alcohol) on the characteristics of poly(styrene
      divinylbenzene) beads for use in affinity chromatography.
AB  - A poly(styrene-divinylbenzene) (PSDVB) chromatography matrix, CG1000-sd
      (TosoHaas), has been modified using poly(vinyl alcohol) (PVA) to create a matrix
      suitable for the attachment of functional groups for the selective purification
      of proteins. The characteristics of the modified matrix have been studied using a
      BET nitrogen adsorption/desorption technique and it has been found that the
      adsorption of PVA results in the bead micropores being filled whilst the bead
      macropores are left essentially unaltered. There was no protein adsorption onto
      the modified matrices. A dye ligand (Procion Blue MX-R) has been covalently
      attached to PVA-PSDVB matrix and the lysozyme capacities of the PVA-PSDVB matrix
      have been determined. The matrix compares well with commercial Blue Sepharose
      Fast Flow, an affinity matrix on cross-linked agarose. The dye-PVA-PSDVB matrix
      is stable when subjected to sanitisation with sodium hydroxide.

PMID- 9181975
TI  - Proceedings of the 20th International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. Part I. San Francisco, California, 16-21 June
      1996.

PMID- 9181974
TI  - Rapid separation of soybean globulins by reversed-phase high-performance liquid
      chromatography.
AB  - A rapid separation of the main soybean proteins (7S and 11S globulins) was
      carried out by reversed-phase high-performance liquid chromatography. For this
      purpose, a linear binary gradient acetonitrile--water--0.1% trifluoroacetic acid,
      at a flow-rate of 1 ml/min and 50 degrees C temperature was designed. Under the
      experimental conditions of this work, it was possible to separate five peaks
      corresponding to the globulins from a soybean protein isolate in 9 min. The
      characterization of soybean proteins was accomplished by analyzing the 7S and 11S
      purified fractions obtained from a soybean protein isolate. The method was
      applied to the separation of soybean proteins from commercial foodstuffs: soybean
      flour, textured soybean and soybean milks.

PMID- 9181976
TI  - [The synergistic action of quaternary ammonium derivatives and inhibitors of
      nitrate reduction in respect to Pseudomonas aeruginosa].
AB  - It was revealed that ability of zink chloride, copper sulphate, aluminium nitrate
      and sodium chloride to inhibit the nitrate reduction of Pseudomonas correlated
      with their potentiating influence on the antimicrobial activity of decamethoxin,
      a quaternary ammonium derivative. So, doses of zink chloride (0.01-0.04%), copper
      sulphate (0.04%), aluminium nitrate (0.04%), sodium fluoride (0.05-0.1%) able to
      inhibit effectively the reduction of anions of nitric acid decreased the minimal
      inhibitory concentration of decamethoxin against Pseudomonas strain ATCC 27853 to
      0.15-10 mg/ml and minimal bactericidal concentration to 0.20-10 mg/ml in
      comparison with 15.6 and 60.4 mg/ml in the control without potentiators.
      Providing the use of respiration chain's inhibiting doses of sodium fluoride
      (0.1%) and zink chloride (0.01%), it became possible to decrease the resistance
      of 54 clinical samples of Pseudomonas aeruginosa to decamethoxin.

PMID- 9181977
TI  - [The content of mimicry antigens in bacteria of the genus Klebsiella when they
      are cultured in plant tissue].
AB  - Bacteria of genus Klebsiella were found to possess group-specific antigens of ABO
      system. Representatives of conditionally pathogenic species, K. rhinoscleromatis,
      K. pneumoniae, K. ozaenae, K. oxytoca, contain 9.4 to 38% of the antigens. In the
      process of interaction of plant organisms and Klebsiella, which passed three
      times in green tomato fruits, the latter have been found to influence some
      biological features of the bacteria which is manifested in the loss of the
      mimicry antigens by a considerable part of the strains as well as in developing
      capsules by some capsule-free variants of klebsiellae.

PMID- 9181978
TI  - [The effect of a vaccinal strain of the plague microbe on C3-receptor expression
      on the surfaces of peritoneal and alveolar macrophages].
AB  - The work is devoted to the effect of vaccine strain of the plague microbe on the
      expression of C3-receptors (C3R) in interaction with macrophages in vitro and in
      vivo. It is established that the activation of macrophages accompanied by the
      increase of C3R expression on the external surface of the membrane of both
      peritoneal and alveolar macrophages occurs in the process of formation of
      antiplague immunity. Maximum activity of C3R in the both populations of
      macrophages is observed on the 7th day after vaccination. Immunization of the
      plague microbe by the vaccine strain does not change the character of response of
      peritoneal and alveolar macrophages to their interaction with this microorganism
      in vitro: a decrease of C3R expression on the surface of the both populations of
      cells obtained from both intact and immunized animals is observed. Heterogeneity
      of the studied populations as to C3R expression both in the intact and immune
      organism is detected.

PMID- 9181979
TI  - [The biological properties of Aerococcus antagonists, representatives of human
      microbiocenoses].
AB  - The paper deals with the data on biology of Aerococcus, a slightly studied group
      of microorganisms. Physiological-biochemical properties of Aerococcus are
      described, data of their distribution in nature are given. Peculiar attention is
      paid to the estimate of the role of Aerococcus in human microbiocenoses. As a
      result of the profound and all-round study of this group of microorganisms the
      authors have developed new bacterial drug "A-bakterin" based on the aerococcus
      strain. Data presented about the results of clinical tests of "A-bakterin" are
      presented, a possibility to use Aerococcus lysate in the elaboration of new drugs
      is discussed.

PMID- 9181981
TI  - [Old and new antibiotics in pneumology].

PMID- 9181980
TI  - [The history of one scientific discussion (strokes in the portrait of Dr. G. S.
      Mosing)].

PMID- 9181982
TI  - [Health workers' knowledge and skills regarding the use of the Turbuhaler
      inhaler].
AB  - The aim of this study was to evaluate health care workers' theoretical knowledge
      and skill in managing the dry powder Turbuhaler. We studied 118 individuals in
      three groups: 50 nurses, 34 medical residents and 34 staff physicians.
      Theoretical knowledge was evaluated by a questionnaire specifically designed for
      the purpose. Skill in managing the device was analyzed by evaluating a practical
      demonstration of the inhaling technique generally recommended, using a placebo
      inhaler. Six percent of staff physicians, 3% of the residents and 2% of the
      nurses answered the theoretical questionnaire correctly. Twenty-one percent of
      the staff physicians, 15% of the residents and 6% of the nurses inhaled
      correctly. However, when skill in managing the inhaler was evaluated against the
      maneuvers recommended by the manufacturer (which do not oblige exhaling before
      inhaling through the device and then holding the breath), there was significant
      improvement: 41% of the staff physicians, 23% of the residents, and 20% of the
      nurses inhaled correctly. We can conclude by saying that: a) our health care
      workers' general knowledge about how to handle the Turbuhaler device is
      deficient; b) the proportion of correct inhalation maneuvers observed doubles
      when these are assessed according to the manufacturer's recommendations, and c)
      health care workers should receive specific training in the inhalation techniques
      required for using the various devices usually prescribed.

PMID- 9181984
TI  - [Surgical treatment of adenotonsillar hypertrophy in children with sleep
      respiratory disorders: changes in polysomnographic patterns].
AB  - Adenotonsillar enlargement (ATE) can cause respiratory disorders during sleep in
      children. The treatment of choice for ATE is adenotonsillectomy and its efficacy
      must be assessed based on improvement in symptoms and polysomnographic patterns.
      We studied 11 children (7 boys and 4 girls, age 5.5 years) whose ATE symptoms
      were corrected by adenotonsillectomy. Two nighttime polysomnograms (SleepLab)
      were recorded, one at baseline and one 6 months after adenotonsillectomy.
      Polysomnographic recordings were analyzed by quantifying 1) only apneic or
      hypopneic events lasting > or = 10 sec and 2) all respiratory events > or = 5
      sec. The most common symptoms were snoring, nocturnal dyspnea and sleep apnea.
      Symptoms resolved after adenotonsillectomy for most patients. Obstructive events,
      in particular shorter apneic events (> or = 5 sec) and instances of hypopnea,
      decreased after surgery. We found no changes in baseline SaO2, although the
      minimum SaO2 improved and the number of desaturations decreased, above all those
      stemming from respiratory events.

PMID- 9181983
TI  - [Clinical assessment systems in the diagnosis of pulmonary thromboembolism].
AB  - We proposed developing two symptom-based systems for assessing the presence of
      pulmonary thromboembolism (TEP) in our practice, using a standardized
      questionnaire and multivariate models. Data were collected from September 1993
      through November 1994 (case reports, physical examination findings and
      complementary test results) of patients admitted to our ward with a suspicion of
      TEP. The calculated odds ratio for each of the variables recorded were used as
      weights to determine their relevance or not for the group at risk for TEP. The
      yield of the two systems developed (a weights system and a logistical model) were
      studied by plotting ROC curves. Eighty-two patients (40 women and 42 men, mean
      age 60.94 +/- 14.39 years) were admitted. The questionnaire had a sensitivity of
      88% and a specificity of 75%, a positive predictive value of 94% and a negative
      predictive value of 60%. The logistical regression model had a sensitivity of
      96.3% for a diagnosis of TEP with inclusion of the following variables: female
      sex, disease-related immobility, presence of deep venous thrombosis (DVT) in the
      lower extremities and the appearance of unexplained dyspnea. Neither system was
      clearly superior to the other for arriving at a clinical diagnosis of TEP.

PMID- 9181985
TI  - [Evolution of pulmonary scintigraphy in the follow-up of pulmonary embolism.
      Effect of anticoagulant treatment and other associated factors].
AB  - We performed a prospective study to determine the evolution of perfusion defects
      6 months after pulmonary thromboembolism (PTE), to identify associated factors
      and to evaluate the incidence of subclinical recurrence. Seventy patients
      diagnosed of PTE were enrolled. Perfusion pulmonary scintiscans were performed 6
      months after the acute PTE episode and the results were compared with initial
      defects. We looked for significant relations between several course profiles and
      factors such as age, sex, anticoagulation therapy and patient history. Defects
      revealed by the initial scintiscan remained the same 6 months later in 15 (21%),
      decreased in 35 (53%) and disappeared in 16 (23%) of the 70 patients. New defects
      were identified in 2 patients. A significant relation was found between a
      favorable outcome as shown by follow-up scintiscans and compliance with
      anticoagulation therapy (p = 0.0024). Other statistically significant relations
      were observed between favorable outcome and a history of surgical intervention
      during the acute episode (p = 0.004) and between unfavorable outcome and a
      history of venous thromboembolic disease (p = 0.004).

PMID- 9181986
TI  - [Peracetic acid: alternative to the sterilization of bronchofibroscopes].
AB  - The Steris system for cold sterilization with peracetic acid was evaluated by
      effecting a series of contaminations of a fiberoptic bronchoscope (FB) with
      specimens of Pseudomonas aeruginosa, Acinetobacter baumanii and Mycobacterium
      kansasi. The FB was contaminated 24 times, 8 times by each microorganism, using
      specimens containing more than 10(8) cfu/ml. After fixing the secretions on the
      FB and washing it with enzyme soap, the BF was sterilized. Specimens were taken
      for culturing after contamination of the FB, after washing, immediately after
      sterilization and 1 hour after sterilization. No microorganism growth of any of
      the samples was detected either immediately after sterilization or one hour
      later. Microbiological data confirmed contamination of the FB after aspiration
      and fixation of the inoculate. Chemical and biological tests with B.
      stearothermophilus spores as specified by the manufacturer were correct in all
      cases: 24 contaminations and 52 processes of prior training. The efficacy of
      washing with enzyme soap before sterilization stands out. In 14 of the 24
      samples, culture was negative after washing and in 7 the concentration of
      microorganisms was less than 500 cfu/ml, which confirms the need for appropriate
      washing before any disinfection or sterilization process is begun. In conclusion,
      the Steris system based on peracetic acid is an alternative to other systems for
      cold sterilization or high level disinfection.

PMID- 9181987
TI  - [Adrenergic beta-2 agonists and their impact on physical performance].
AB  - That asthmatics benefit not only from physical exercise but that they can even
      reach performance levels comparable to that of non asthmatics is becoming
      increasingly clear. To reach such a level, asthmatics need to use drugs to
      prevent effort-related asthma attacks in addition to taking appropriate
      therapeutic measures. beta 2 agonists are drugs that potentially produce a
      certain amount of "anabolic" effect, depending on the dose and permanence in
      tissues, in laboratory and farm animals as well as in humans. We must conclude
      that the dose needed to obtain this effect is higher than that used for
      therapeutic purposes in asthma or respiratory diseases. Bearing in mind that oral
      treatments are considerably less effective than inhaled drugs in exercise-related
      asthma attacks, that the doses of the latter are lower and that the ergogenic
      effects of the substances studied are nil or below detection levels, it seems
      logical to allow individuals with asthma who use such substances to engage in
      physical exercise. Moreover, the asthmatic whose disease is so severe as to
      require the use of orally administered beta 2 agonists will in all likelihood be
      too ill to participate in a sport while that status persists.

PMID- 9181988
TI  - [Sleep respiratory disorders in fibromyalgia syndrome].

PMID- 9181989
TI  - [Primary pulmonary hypertension: treatment with prostacyclin before lung
      transplantation].
AB  - We report our experience with two patients diagnosed of primary pulmonary
      hypertension who later received lung transplants, with treatment with short
      acting pulmonary vasodilators (epoprostenol) provided as a bridge to
      transplantation. Continuous intravenous perfusion at a dose of 6 ng/kg/min was
      provided to the first patient, a 19-year-old man, for 26 days. An initial dose of
      4 ng/kg/min followed by 6 ng/kg/min was given to the second patient, a 49-year
      old woman, for 6 months. Symptoms were drastically reduced in both patients,
      significantly improving their quality of life.

PMID- 9181990
TI  - [Conservative treatment of 2 tracheal lesions secondary to anesthetic
      intubation].
AB  - This case report describes two patients admitted to our hospital for elective
      surgery, one for biliary disease and the other for vascular disease. Shortly
      after surgery each presented a clinical picture attributable to membranous
      tracheal pars rupture caused by anesthetic intubation. Airway lesions were
      diagnosed and, after patient status was evaluated, conservative medical treatment
      was prescribed in both cases. Outcome was excellent, with no complications,
      within a few days. These cases demonstrate the efficacy of this way of managing
      this potentially serious complication.

PMID- 9181992
TI  - [Upper airway obstruction in patients with chronic obstructive pulmonary
      disease].

PMID- 9181991
TI  - [Mediastinal non-Hodgkin's lymphoma: atypical presentation diagnosed with
      bronchoscopy].
AB  - Primary mediastinal non-Hodgkin lymphoma is a rare entity that can manifests with
      secondary pulmonary involvement. The case of a 37 years-old man patient with non
      Hodgkin lymphoma mixed B-cell, which was diagnosed by means of bronchoscopic
      biopsy, is presented. His characteristics clinical and radiologic presentation,
      and diagnostic usefulness of fiberoptic bronchoscopy, is remarked. We revised
      clinical and pathologic features of interests for this lymphoproliferative
      disorders with thoracic involvement.

PMID- 9181993
TI  - [Epidermoid carcinoma with extensive bone metastasis and normal scintigraphy].

PMID- 9181994
TI  - [Home oxygen therapy: is it time to review its indications?].

PMID- 9181995
TI  - Chlorinated Dioxins, PCB and Related Compounds 1995. Proceedings of the 15th
      International Symposium. Edmonton, Canada, 21-25 August 1995.

PMID- 9181996
TI  - [Cardiac sudden death in adults].
AB  - Sudden death is becoming a matter for concern as this type of accident represents
      an increasing proportion of deaths from cardio-vascular causes. A campaign is
      being launched aimed at promoting early diagnosis and appropriate action at the
      time of the event itself. At the same time it is necessary to get to know the
      target population better, especially with regard to the specific anatomical
      conditions which are the cause of death. For the last seven years we have been
      carrying out a descriptive pathological research study. The first stage took form
      of a three year retrospective study (1989-1991) involving 365 subjects victims of
      sudden death. The second part was a prospective study carried out in 1994. Heart
      disease emerged as the principal cause of death, something which is already well
      known. More interesting was the discovery that 72.3% of the subjects were
      completely asymptomatic despite the fact that in 85% of cases they had bi-truncal
      or tri-truncal lesions. The same findings emerged from the study of a subgroup of
      persons who had died suddenly as a result of acute stress. The data obtained are
      extremely homogeneous. When compared to the findings obtained from a control
      group of the same age who had died as the result of violence, the difference
      between the two populations is highly significant. Finally we should like to draw
      attention to the lack of epidemiological data on sudden death available in France
      at the present time, and this despite the fact that it is undoubtedly a public
      health priority. There is a need to promote both education and action in relation
      to this somewhat disturbing subject.

PMID- 9181998
TI  - [Good fortune and misfortune of the medical economy].

PMID- 9181997
TI  - [First experience in treatment of terminal cardiac insufficiency using multisite
      stimulation].
AB  - We hypothesized that the presence of an abnormal ventricular mechanical
      activation sequence and/or a delayed left ventricular (LV) contraction may have
      adverse hemodynamic effects in congestive heart failure (CHF) and could be
      improved by synchronous RV-LV pacing in a multisite (MS) configuration. 8 NYHA IV
      CHF patients were included with a LV delay due to 1/ preexistent pacemaker in 4
      pts (2 VVI and 2 DDD); 2/ left bundle branch block in 2 pts; 3/ intraventricular
      conduction delays in 2 pts. An acute hemodynamic evaluation was performed.
      Hemodynamics were optimized in standard RV pacing by modifying RV lead position
      from apex to outflow tract (RVOT) in VVI for AF patients and in VDD for sinus
      rhythm patients at different AV delays. RV pacing did not change hemodynamics
      whatever the lead position. BV pacing improved CI by 25% (p < 0.006), V wave by
      26% (p < 0.004) and PCWP by 17% (p < 0.01). Chronic implantation was performed in
      7pts. LV lead was implanted via the coronary sinus in 2 cases and epicardial via
      a thoracoscopic approach in the remaining ones. 1 pt died during LV lead
      implantation. Hemodynamics were tested at 2 months followup (FU). Switching BV
      pacing off was associated with immediate deterioration. At 6 +/- 6 months
      Followup 4 pts are stable in Class II. 1 pt died of cardiac cause. 1 pt could be
      transplanted at 17 months FU. In conclusion, BV pacing through a multisite
      configuration is feasible and can help in CHF patients managing.

PMID- 9181999
TI  - [Contemporary trends of the law of responsibility].

PMID- 9182000
TI  - [Human and animal spongiform encephalopathy. Update on December 17, 1996].
AB  - Recent papers about bovine spongiform encephalopathy (BSE) and new variant of
      Creutzfeldt-Jakob disease (nvCJD) are reviewed: new data, maternal transmission
      of BSE, epidemiology of BSE in British cattle, structure of the PrP(res),
      biochemical signature of PrP(res), chronic pesticide-initiated modification of
      the prion protein, protein markers in cerebrospinal fluid.

PMID- 9182001
TI  - [Hysteroscopic resection of the endometrium: an alternative to hysterectomy?].
AB  - A study carried out on 342 cases of endometrial resection, with a follow up of 3
      to 36 months, has allowed us to precise: 1. The indications of this technique:
      patients more than 40 years, suffering of abnormal uterine bleeding. 2. The
      endometrial ablation was performed by electrosurgery through an operating channel
      of the hysteroscopic sheet (9 mm) and with a glycocol distended media (1.5%). The
      mean time to complete the operation was 35 +/- 10 minutes, the mean length of the
      hospital stay was 1 day. We had no serious complications. 3. And the rate of
      success (amenorrhea or hypomenorrhea) was 95% at 3 months but decreased at 90% at
      36 months. The rate of secondary hysterectomy was 10%, due to the associated
      lesions: myoma with adenomyosis in 50% of the cases. There was some evidence of
      superior health related quality of life among hysterectomy patients. It's the
      reason why it is necessary to make a serious selection of the patients who are to
      be treated by this method in order to avoid complications and secondary
      hysterectomy.

PMID- 9182002
TI  - [The surgeon, the expert, the judge].
AB  - A study of 125 medico-legal opinions and evaluation of the literature allows for:
      an appreciation of the evolution in the concept in the jurisprudence pertaining
      to the responsibility of the surgeon in France in present practice conditions, a
      definition of the role of the legal expert, an explanation of the development of
      paths outside the procedural setting. In the present state of our knowledge the
      responsibility related to a prejudicial error has a frequency of 25-30% all
      jurisdictions and disciplines considered together. In 66% of cases the error is
      the absence of a timely treatment decision or a defective postoperative follow
      up. A mishap without proven error is present 50% of the cases which justifies a
      decision of coverage outside the civil responsibility of the surgeon. The modern
      conditions of surgical practice, the implications of the new technologies, the
      evolution of economic and socio-cultural ideas must lead the political decision
      makers and health-professionals to rapidly define a clear line of conduct. In the
      absence of comprehensive statistics from the courts, the qualitative and
      quantitative information contained in the national database "Remedhos France",
      now available, will be useful to inform the surgical community on the risk and
      its prevention, as well as to orient a homogenous doctrine and its applications
      in view of a common European approach.

PMID- 9182003
TI  - [The use of the low-energy helium-neon laser in the surgical treatment of acute
      complicated cholecystitis].

PMID- 9182004
TI  - [The interrelation of bile micellization and lithogenicity].

PMID- 9182005
TI  - [The blood circulation of the liver in cirrhosis with the portal hypertension
      syndrome].

PMID- 9182006
TI  - [Clinico-diagnostic parallels of lung hypoplasia in children].

PMID- 9182008
TI  - [The comparative evaluation of the data from ultrasonic study of the thyroid
      gland and of the results of surgical treatment with subsequent histological study
      of the removed tissues].

PMID- 9182007
TI  - [The clinical efficacy of the preparation Oframax in patients with a suppurative
      surgical infection].

PMID- 9182009
TI  - [Soft-tissue contour plastic repair using the hydrophilic polyacrylamide gel PAAG
      Interfall].

PMID- 9182010
TI  - [Laparoscopic cholecystectomy. The initial results and the outlook].

PMID- 9182011
TI  - [The potentials of ultrasonic duplex dopplerography in the early diagnosis of the
      dysfunction of a kidney allograft].

PMID- 9182012
TI  - [The initial status of patients with insulinoma as a factor in selecting the
      method of anesthesia].

PMID- 9182013
TI  - [The importance of the morphometric analysis of peripheral blood lymphocytes in
      the diagnosis of thyroid diseases].

PMID- 9182014
TI  - [An improvement in the methods of surgical intervention for cancer of the
      oropharynx].

PMID- 9182015
TI  - [The use of endoprosthesis in treating tracheal and bronchial stenosis].

PMID- 9182016
TI  - [Thermal diagnostic methods in medicine].

PMID- 9182017
TI  - [Laser correlation spectroscopy--a biophysical method for the differential
      diagnosis of jaundice of different origins].

PMID- 9182018
TI  - [The choice of the bile-diverting operation for unresectable cancer of the
      pancreas and periampullary area].

PMID- 9182019
TI  - [Ectodermal dysplasia: multiple manifestations of a hereditary disease].
AB  - Ectodermal dysplasia is a hereditary disease that can manifest itself in many
      ways. Four cases, including two cases involving heterozygote twins, are
      presented. The clinical signs of the disease, as observed are compared to the
      knowledge offered in the classic and modern literature. Special attention is
      given to the intraoral manifestations of the disease, and to the solutions that a
      multidisciplinary dental team could consider to improve the masticatory function
      and the facial esthetics of patients affected by this disease.

PMID- 9182020
TI  - Forewarned is forearmed, but forestalled?

PMID- 9182021
TI  - Providing cost-effective therapy using pharmacoeconomic evaluations: the public
      sector approach.
AB  - Four years ago it became obvious within the US Department of Defense (DOD) that
      expenditures for pharmaceuticals and health care were escalating beyond control.
      Realizing this upward pressure on costs was one of the major trends jeopardizing
      the military health care system, which cares for 8 million-plus beneficiaries,
      the DOD began using pharmacoeconomics to manage pharmacy expenditures. The DOD
      has several competing goals: to reduce pharmaceutical expenditures within the
      context of an open formulary while maintaining optimum patient care; provide
      practitioners, pharmacists, and administrators with the information they need to
      make cost-effective choices in pharmacotherapy; and provide for a consistent and
      equitable pharmacy benefit throughout the DOD based on cost-effective
      recommendations. Currently used methods for pharmacoeconomics did not meet the
      DOD's needs, so it turned to applied pharmacoeconomics. This paper discusses the
      use of applied pharmacoeconomics as it pertains to the DOD.

PMID- 9182023
TI  - The clinical usefulness of measurement of the reticulocyte count and its
      maturation parameters. Proceedings of a symposium. Nice, France, June 1994.

PMID- 9182024
TI  - [Percutaneous dilatative tracheostomy as a new method in intensive medicine.
      Procedure, advantages and risks].
AB  - BACKGROUND AND OBJECTIVE: Percutaneous dilatational tracheostomy (PDT) is a
      recently developed method to obtain endotracheal access, also at the bed-side, in
      ventilated patients. The procedure is described and results are presented.
      PATIENTS AND METHODS: PDT was performed in 112 patients (82 men, 30 women,
      average age 50.7 years) between 1.5. 1994 and 31.5. 1996, in all cases expected
      to require more than 10 days of assisted ventilation. All complications, late
      sequelae and cosmetic results after decannulation were analysed. RESULTS: No
      serious complications were noted during the procedure. Erroneous puncture
      occurred in nine patients, but were corrected without problem. Complications
      necessitating temporary interruption of the tracheostomy consisted of accidental
      extubation and ventilatory problems (two patients each). There were no late
      sequelae and the cosmetic results were judged to be very good. CONCLUSION: PDT is
      a simple and relatively easily learned procedure. It has a low complication rate,
      late sequelae are very rare and cosmetic results after closure of the
      tracheostomy are excellent.

PMID- 9182022
TI  - A pharmacoeconomic evaluation of the use of dexrazoxane in preventing
      anthracycline-induced cardiotoxicity in patients with stage IIIB or IV metastatic
      breast cancer.
AB  - A Markov model was developed to determine the cost of treating patients with
      stage IIIB or IV metastatic breast cancer with 5-fluorouracil, doxorubicin, and
      cyclophosphamide (FAC) and dexrazoxane (administered after six courses of FAC)
      versus FAC alone. The primary end point in our economic study was cost per
      cardiac event avoided. Cost per life-year saved was also calculated, even though
      the survival advantage needs to be confirmed in follow-up studies. The model
      incorporated the direct medical costs of treating patients with chemotherapy, as
      well as the costs associated with treatment of any cardiac events that occurred.
      Data were collected for this analysis from several sources, including completed
      clinical trials on FAC plus dexrazoxane versus FAC plus placebo (obtained from
      two patient groups randomized at different time points), a panel of three
      oncologists, and a panel of three cardiologists. Analyses showed that therapy
      with dexrazoxane costs $5661.77 per cardiac event prevented. Sensitivity analyses
      on model variables were performed and showed that the basic results of the model
      did not change when parameters were varied. The clinical efficacy and cost
      effectiveness of dexrazoxane as shown by the results of the current study
      encourage further investigation of the uses of dexrazoxane in other populations
      and against other comparators.

PMID- 9182025
TI  - [Complete gastric wall necrosis after endoscopic sclerotherapy for a gastric
      ulcer with visible arterial stump].
AB  - HISTORY AND CLINICAL FINDINGS: A 43-year-old man with a gastric ulcer was
      admitted because of sudden onset of epigastric pain, cold sweats and dizziness.
      He had tachycardia (100/min); his blood pressure was 120/80 mm Hg: his
      epigastrium was tender to palpation. There were no tarry stools. INVESTIGATIONS:
      Haemoglobin concentration was 12.7 g/dl. WBC count 17,900/microliter. Gastroscopy
      revealed residual haematin and an ulcer with an arterial stump at the angular
      fold. TREATMENT AND COURSE: 3 ml epinephrine, diluted 1:20,000, and 13 ml of 1%
      polidocanol were injected around the arterial stump, most of the latter solution
      flowing back into the gastric lumen from the rather hard ulcer base. Haematemesis
      four days later necessitated laparotomy followed by gastrectomy with
      reconstruction and a Roux-Y anastomosis because of complete necrosis of the
      gastric wall. Histological examination of the surgical specimen showed chronic
      scarred gastric ulcer and ulcerating pangastritis with haemorrhagic necrosis of
      the wall and associated peritonitis, caused by accidental injection of
      polidocanol into the artery. CONCLUSION: Since the tissue-sparing injection of
      epinephrine, fibrin glue or salt solution is alone effective in the endoscopic
      treatment of bleeding gastroduodenal ulcers, polidocanol should not be injected
      as well.

PMID- 9182027
TI  - [Therapy of primary hepatocellular carcinoma].

PMID- 9182026
TI  - [Costosternal swelling and diffuse bone pain in tubercular osteomyelitis].
AB  - HISTORY AND CLINICAL FINDINGS: For about a year a 28-year-old Nigerian had been
      suffering from diffuse bone pain, intermittent fever, weight loss and weakness.
      Physical examination was unremarkable except for a swelling at the sternal angle.
      INVESTIGATIONS: The tuberculin test was clearly positive and tests for
      inflammatory disease were elevated, but the chest radiograph was normal. Bone
      scintigraphy demonstrated multiple sites of increased storage in the ribs and
      vertebral column. Magnetic resonance imaging revealed a large paravertebral
      abscess, which was needled under computed tomography monitoring. Polymerase chain
      reaction of the aspirate demonstrated Mycobacterium tuberculosis. TREATMENT AND
      COURSE: While initial treatment with combined isoniazid, streptomycin, rifampicin
      and pyrazinamide, the first two drugs had to be discontinued, the microorganism
      not being sensitive to them, and were replaced by ethambutol and amikacin. The
      abscess was drained and the vertebral fracture surgically stabilised. There were
      no neurological abnormalities and the lesions largely healed. CONCLUSION: Even
      without pulmonary involvement tuberculosis must be included in the differential
      diagnosis of rheumatic diseases with joint and vertebral column involvement, such
      as the SAPHO syndrome and other inflammatory bone diseases.

PMID- 9182028
TI  - [Endocrine disorders and hormonal therapy in HIV infections].

PMID- 9182029
TI  - [Prohibition of competition for practice assistants in promotion. Verdict of the
      Federal Court on June 13, 1996].

PMID- 9182030
TI  - [Sudden cardiac death in young men].

PMID- 9182031
TI  - Role of the neurologist in hazard identification and risk assessment.
AB  - This review describes strategies used by a clinical neurologist in the
      investigation of neurotoxic disease. It emphasizes the need for a high level of
      suspicion that environmental substances are capable of producing impairments in
      neurologic and neurobehavioral functions. Because of the difficulties in
      differentiating neurotoxic from nonneurotoxic disease when presented with common
      neurological symptoms, it is necessary to rely upon corroborative evidence from
      past medical records, work and environmental histories, and exposure data, as
      well as detailed neurological examinations, to reach a conclusion about
      causation. Sensitive electrophysiologic and neuropsychologic test batteries are
      useful in identifying subclinical impairments and in providing objective
      confirmation of abnormalities in the central and peripheral nervous systems.
      Combining scientific and epidemiologic information with experience and clinical
      judgment, these sources of information are used in the formulation of a clinical
      diagnosis. When many patients among a group of people are exposed to
      neurotoxicants, the effects of the exposure may vary from one to another because
      of differences in susceptibility, duration of exposure and dosage of
      neurotoxicant, and other possible risk factors. Group statistics may obscure a
      significant effect for the larger group, despite clinically obvious effects in an
      individual. The neurologist applies clinical skills and refers to the accumulated
      neurotoxicologic literature as a frame of reference to make a diagnosis about an
      individual patient or a group of patients who have been exposed to particular
      neurotoxicants. The Boston University Environmental Neurology Assessment (BUENA)
      is a scheme that attempts to combine epidemiologic methodology and clinical
      approaches to detect effects of neurotoxic exposure. The advantages and
      limitations of such a strategy are discussed.

PMID- 9182032
TI  - Neuropsychological approaches for the detection and evaluation of toxic symptoms.
AB  - The purpose of this paper is 3-fold: a) to review briefly the neuropsychological
      tests that have been used to evaluate the effects of neurotoxicants; b) to
      identify individual factors that may create heightened sensitivity to
      neurotoxicants; and c) to discuss test parameters that will increase the
      sensitivity of neuropsychological tests for detecting symptoms in low-level
      exposure situations. While the body of literature on neurobehavioral toxicology
      has increased dramatically during the past 10 years, it remains difficult to
      discern which tests are most effective in detecting behavioral effects even among
      workers with significant exposures. Few investigators have evaluated the
      interactions between individual differences, such as gender and psychiatric
      function, and exposure to neurotoxicants. Detection of behavioral performance
      decrements among uniquely susceptible populations such as those with
      sensitivities to low-level exposures (e.g., multiple chemical sensitivities) will
      require more difficult tests than are frequently used in current
      neuropsychological test batteries.

PMID- 9182034
TI  - Prospective, longitudinal assessment of developmental neurotoxicity.
AB  - Methodological issues in the design of prospective, longitudinal studies of
      developmental neurotoxicity in humans are reviewed. A comprehensive assessment of
      potential confounding influences is important in these studies because inadequate
      assessment of confounders can threaten the validity of causal inferences drawn
      from the data. Potential confounders typically include demographic background
      variables, alcohol and smoking during pregnancy, the quality of parental
      stimulation, the child's age at test, and the examiner. Exposure to other
      substances is assessed where significant exposure is expected in the target
      population. In most studies, control variables even weakly related to outcome are
      included in all multivariate statistical analyses, and a toxic effect is inferred
      only if the effect of exposure is significant after controlling for the potential
      confounders. Once a neurotoxic effect has been identified, suspected mediating
      variables may be added to the analysis to examine underlying processes or
      mechanisms through which the exposure may impact on developmental outcome.
      Individual differences in vulnerability may be examined in terms of either an
      additive compensatory model or a synergistic "risk and resilience" approach.
      Failure to detect real effects (Type II error) is of particular concern in these
      studies because public policy considerations make it likely that negative
      findings will be interpreted to mean that the exposure is safe. Important sources
      of Type II error include inadequate representation of highly exposed individuals,
      overcontrol for confounders, and inappropriate correction for multiple
      comparisons. Given the high cost and complexity of prospective, longitudinal
      investigations, cross-sectional pilot studies focusing on highly exposed
      individuals can be valuable for the initial identification of salient domains of
      impairment.

PMID- 9182033
TI  - Performance tests.
AB  - This paper discusses the use of psychological performance tests to assess the
      effects of environmental stressors. The large number and the variety of
      performance tests are illustrated, and the differences between performance tests
      and other psychological tests are described in terms of their design,
      construction, use, and purpose. The stressor emphasis is on the effects of drugs
      since that is where most performance tests have found their main application,
      although other stressors, e.g., fatigue, toxic chemicals, are mentioned where
      appropriate. Diazepam is used as an example. There is no particular performance
      emphasis since the tests are intended to have wide applicability. However,
      vehicle-driving performance is discussed because it has been the subject of a
      great deal of research and is probably one of the most important areas of
      application. Performance tests are discussed in terms of the four main underlying
      models--factor analysis, general information processing, multiple resource and
      strategy models, and processing-stage models--and in terms of their psychometric
      properties--sensitivity, reliability, and content, criterion, construct, and face
      validity. Some test taxonomies are presented. Standardization is also discussed
      with reference to the reaction time, mathematical processing, memory search,
      spatial processing, unstable tracking, verbal processing, and dual task tests
      used in the AGARD STRES battery. Some comments on measurement strengths and
      appropriate study designs and methods are included.

PMID- 9182036
TI  - Ethological and experimental approaches to behavior analysis: implications for
      ecotoxicology.
AB  - Laboratory research in toxicology has progressed far beyond reliance on measures
      of mortality to make use of sophisticated behavioral preparations that can
      evaluate the consequences of sublethal toxicant exposure. In contrast, field
      studies have not evolved as rapidly. Approaches developed by experimental
      psychologists and ethologists provide powerful and complementary methodologies to
      the study of environmental pollutants and behavior. Observational data collection
      techniques can easily be used to broaden the number of questions addressed
      regarding sublethal exposure to toxic agents in both field and laboratory
      environments. This paper provides a background in such techniques, including
      construction of ethograms and observational methodologies, and the use of
      laboratory analogues to naturally occurring activities such as social behavior,
      predation, and foraging. Combining ethological and experimental approaches in
      behavior analysis can result in a more comprehensive evaluation of the effects of
      environmental contaminants on behavior.

PMID- 9182035
TI  - Economical test methods for developmental neurobehavioral toxicity.
AB  - The assessment of behavioral changes produced by prenatal or early postnatal
      exposure to potentially noxious agents requires both the designing of ad hoc
      tests and the adaptation of tests for adult animals to the characteristics of
      successive developmental stages. The experience in designing tests is still more
      limited than in the adaptation of tests, but several tests have already proven
      their usefulness; some examples are the suckling test, the homing test, and
      evaluations of dam-pup and pup-pup interactions. Functional observational
      batteries can exploit the development at specified postnatal ages of several
      reflexes and responses that are absent at birth in altricial rodent species with
      a short pregnancy such as the rat and the mouse. In neonates, the assessment of
      early treatment effects can rely not only on deviations from normal responding
      but also on changes in the time of appearance of otherwise normal response
      patterns. The same applies to other end points such as responses to pain and
      various types of spontaneous motor/exploratory activities, including reactivity
      to a variety of drug challenges that can provide information on the regulatory
      systems whose development may be affected by early treatments. In particular, the
      analysis of ontogenetic dissociations (i.e., differential early treatment effects
      depending jointly on developmental stage at the time of exposure, age of testing,
      and response end point) can be of considerable value in the study of treatments'
      mechanisms of action. Overall, it appears that behavioral teratological
      assessments can be effectively used both proactively, i.e., in risk assessment
      prior to any human exposure, and reactively. In the latter case, these
      assessments could have special value in the face of agents suspected to produce
      borderline changes in developing humans, whose innocuousness or noxiousness can
      be difficult to establish in the absence of hard evidence of teratogenicity.

PMID- 9182037
TI  - Appropriate end points for the characterization of behavioral changes in
      developmental toxicology.
AB  - The present paper is devoted to second- and higher-tier test methods for the
      characterization of behavioral changes produced in rodents by exposure to noxious
      agents during development. The paper analyzes a series of end points that are
      informative about specific processes and underlying regulatory mechanisms but
      require greater technical sophistication and larger investments than first-tier
      end points. This applies to ultrasonic emissions in successive postnatal periods;
      to mother-pup interactions, including appropriate cross-fostering controls; to
      social (including sexual) interaction tests from the infantile to the young adult
      stage; and to a variety of conditioning and learning tests using both positive
      and negative reinforcement.

PMID- 9182038
TI  - Comprehensive neurotoxicity assessment.
AB  - Significant progress has been made in recent years in terms of both the
      conceptualization of neurotoxicity assessment strategies as well as in the
      development of behavioral techniques for evaluating neurotoxic exposures. A
      tiered approach, for example, has been advocated as an assessment strategy in
      which testing would proceed in a stepwise fashion from general screening using
      simple behavioral methods and neuropathology (tier 1) to the characterization of
      effects (tier 2) using more specific testing techniques. With respect to tier-1
      testing, behavioral observational methods have been standardized for screening
      purposes, and these technically simple techniques, together with automated
      methods for motor activity assessment, are being increasingly incorporated into
      chemical and drug safety evaluations for regulatory purposes. With respect to
      tier-2 testing, more technically sophisticated techniques and behavioral
      paradigms are available for characterizing the behavioral effects of chemical
      exposures on motor, sensory, and cognitive processes. Paradigms involving learned
      and unlearned behavior, for example, have been described for quantifying a
      variety of clinical signs of motor impairment including paretic gait disorders,
      tremor, and coordination deficits. Likewise, robust noninvasive behavioral
      methods capable of tracking changes in visual, auditory, and somatosensory
      thresholds during the course of exposure are also available. With respect to
      cognitive testing, numerous maze and operant techniques and paradigms measuring
      different aspects of performance, learning, and memory have been elaborated. This
      paper presents an overview of behavioral techniques currently used to assess
      neurotoxicity in adult laboratory animals and discusses their application to
      hazard identification and other areas of risk assessment.

PMID- 9182039
TI  - Clinical neurologic indices of toxicity in animals.
AB  - The fundamental structures and functions of the nervous systems of animals and
      humans are conserved in many ways across species. These similarities provide a
      basis for developing common neurologic examinations for a number of species of
      animals and also provide a basis for developing risk assessments across species
      for neurologic end points. The neurologic examination requires no expensive
      equipment and can be conducted in the field or wherever impaired animals are
      identified. The proper conduct of neurologic examinations in animals assumes that
      the examiner has a fundamental understanding of the normal structure and function
      of the nervous system as well as knowledge about the spontaneous disease
      background of the species being studied.

PMID- 9182040
TI  - Disrupted patterns of behavior in natural populations as an index of ecotoxicity.
AB  - This paper examines behavioral changes in natural populations of wildlife
      associated with pollution. Although some changes such as lack of nest
      attentiveness and decreased nest defense have been noted, the results have not
      been consistent and have been difficult to relate to specific pollutants.
      Experimental studies involving lead, mercury, and organochlorine and
      organophosphate insecticides are described. Although changes in behavior have
      been observed, they are generally more difficult to quantify and are less
      reproducible than biochemical changes. To date, there is no clear evidence in
      wildlife that behavioral changes caused by pollutants are a serious threat to
      populations.

PMID- 9182041
TI  - Behavioral effects of lead: commonalities between experimental and epidemiologic
      data.
AB  - Enormous effort has been focused over the last decade and a half on
      characterizing the behavioral effects of lead in the developing organism. While
      age-appropriate standardized measures of intelligence (IQ) have been the
      dependent variable most often used to assess lead-induced cognitive impairment in
      epidemiologic studies, researchers have also used a variety of other methods
      designed to assess specific behavioral processes sensitive to lead. Increased
      reaction time and poorer performance on vigilance tasks associated with increased
      lead body burden suggest increased distractibility and short attention span.
      Assessment of behavior on teachers' rating scales identified increased
      distractibility, impulsivity, nonpersistence, inability to follow sequences of
      directions, and inappropriate approach to problems as hallmarks of lead exposure.
      Robust deficits in learned skills such as reading, spelling, math, and word
      recognition have also been found. Spatial organizational perception and abilities
      seem particularly sensitive to lead-induced impairment. Assessment of complex
      tasks of learning and memory in both rats and monkeys has revealed overall
      deficits in function over a variety of behavioral tasks. Exploration of
      behavioral mechanisms responsible for these deficits identified increased
      distractibility perseveration, inability to inhibit inappropriate responding, and
      inability to change response strategy as underlying deficits. Thus, there is
      remarkable congruence between the epidemiologic and experimental literatures with
      regard to the behavioral processes identified as underlying the deficits
      inflicted by developmental lead exposure. However, careful behavioral analysis
      was required from researchers in both fields for such understanding to emerge.

PMID- 9182042
TI  - Behavioral toxicology, risk assessment, and chlorinated hydrocarbons.
AB  - Behavioral end points are being used with greater frequency in neurotoxicology to
      detect and characterize the adverse effects of chemicals on the nervous system.
      Behavioral measures are particularly important for neurotoxicity risk assessment
      since many known neurotoxicants do not result in neuropathology. The chlorinated
      hydrocarbon class consists of a wide variety of chemicals including
      polychlorinated biphenyls, clioquinol, trichloroethylene, hexachlorophene,
      organochlorine insecticides (DDT, dicofol, chlordecone,dieldrin, and lindane),
      and phenoxyherbicides. Each of these chemicals has effects on motor, sensory, or
      cognitive function that are detectable using functional measures such as
      behavior. Furthermore, there is evidence that if exposure occurs during critical
      periods of development, many of the chlorinated hydrocarbons are developmental
      neurotoxicants. Developmental neurotoxicity is frequently expressed as
      alterations in motor function or cognitive abilities or changes in the ontogeny
      of sensorimotor reflexes. Neurotoxicity risk assessment should include
      assessments of the full range of possible neurotoxicological effects, including
      both structural and functional indicators of neurotoxicity.

PMID- 9182043
TI  - Behavioral methods and organic solvents: questions and consequences.
AB  - This paper reviews some illustrative examples of studies of human neurobehavioral
      effects from experimental as well as long-term occupational organic-solvent
      exposure. My objective is to present a selection of neurobehavioral solvent
      studies with the educational aim that we may hopefully learn from the early
      experiences of others. Some of the methodological problems encountered in these
      studies are discussed, as well as some reasons for the relative success of the
      work performed by certain Scandinavian research teams.

PMID- 9182045
TI  - The challenge of mechanism-based modeling in risk assessment for neurobehavioral
      end points.
AB  - The mathematical form for a dose-time-response model is ideally not just a
      convenience for summarizing or fitting a particular data set--it represents a
      hypothesis. The more this hypothesis reflects a mechanistically sophisticated
      view of the likely reality, the more it can lead to potentially informative
      validating or invalidating types of predictions about the results of real
      experiments and (in the long run) reasonably credible predictions outside the
      range of direct observations. This paper first reviews some distinctive features
      of the nervous system and neurotoxic responses and theoretically explores some
      basic quantitative implications of these features. Relationships are derived for
      how dose-response relationships for the inhibition of function should depend on
      the numbers of neurons in series or redundant parallel arrangements that are
      required or capable of performing the function. Previous work is reviewed in
      which some less nervous-system-specific features were the foci of quantitative
      risk-assessment modeling for specific neurotoxic end points. These include a)
      rates of repair of putatively reversible damage in the case of acrylamide; b)
      human interindividual variability in susceptibility to fetal/developmental
      effects in the case of methylmercury; and c) opportunities to use intermediate
      biomarkers to assist in integrated animal toxicological and epidemiologic
      investigations of the chronic cumulative risks posed by agents that contribute to
      neuronal loss with increasing age and pathology.

PMID- 9182044
TI  - Evolution of our understanding of methylmercury as a health threat.
AB  - Methylmercury (MeHg) is recognized as one of the most hazardous environmental
      pollutants, primarily due to endemic disasters that have occurred repeatedly. A
      review of the earlier literature on the Minamata outbreak shows how large-scale
      poisoning occurred and why it could not be prevented. With the repeated
      occurrences of MeHg poisoning, it gradually became clear that the fetus is much
      more susceptible to the toxicity of this compound than the adult. Thus, recent
      epidemiologic studies in several fish-eating populations have focused on the
      effects of in utero exposure to MeHg. Also, there have been many studies on
      neurobehavioral effects of in utero exposure to methylmercury in rodents and
      nonhuman primates. The results of these studies revealed that the effects
      encompass a wide range of behavioral categories without clear identification of
      the functional categories distinctively susceptible to MeHg. The overall
      neurotoxicity of MeHg in humans, nonhuman primates, and rodents appears to have
      similarities. However, several gaps exist between the human and animal studies.
      By using the large body of neurotoxicologic data obtained in human populations
      and filling in such gaps, we can use MeHg as a model agent for developing a
      specific battery of tests of animal behavior to predict human risks resulting
      from in utero exposure to other chemicals with unknown neurotoxicity. Approaches
      developing such a battery are also discussed.

PMID- 9182046
TI  - Dose-response analysis in risk assessment: evaluation of behavioral specificity.
AB  - Several methods of quantitative risk assessment that have been described recently
      are particularly applicable to neurotoxic end points. These methods can be
      broadly divided into two types of approaches based on their treatment of dose
      response data to estimate risks. Benchmark approaches estimate risks using
      variability in response to a fixed dose level in comparison with background
      control variability. Probabilistic approaches estimate risks using the
      variability in the dose to produce a small effect in the sample population. The
      current report seeks to extend the development of probabilistic approaches for
      neurotoxic end points. Because behavioral data are often used to assess
      therapeutic efficacy as well as toxicity (unwanted effects), this analysis
      focused on the relative risks of producing these effects with the same agent. The
      therapeutic potential of GBR 12909 was determined by its ability to decrease
      cocaine-maintained responding in monkeys. The effects of this agent were also
      assessed in the same monkeys using food-maintained responding to provide an
      indication of behavioral toxicity. GBR 12909 decreased both behaviors, with
      complete decreases on drug-seeking behavior occurring at doses that had minimal
      effects on food-maintained responding. The difference in the estimates of doses
      to decrease drug-seeking and food-maintained behavior suggested that specific
      therapeutic effects could be obtained in the absence of unwanted side effects for
      a definable proportion of the population. These results also suggest that
      multiple behavioral end points can be useful for identifying specific effects of
      chemicals for the purposes' of risk assessment.

PMID- 9182047
TI  - Neurobehavioral epidemiology: application in risk assessment.
AB  - Neurobehavioral epidemiology may contribute information to risk assessment in
      relation to a) characterization of neurotoxicity and its time course; b) the dose
      effect relationship; c) the dose-response relationship; and d) predisposing
      factors. The quality of this information relies on the validity of the exposure
      data, the validity and sensitivity of neurobehavioral function tests, and the
      degree to which sources of bias are controlled. With epidemiologic studies of
      methylmercury-associated neurotoxicity as an example, the field of research
      involves numerous uncertainties that should be taken into account in the risk
      assessment process.

PMID- 9182048
TI  - Setting exposure standards: a decision process.
AB  - Increased emphasis on routine screening of chemicals for potential neurotoxicity
      has resulted in the development of testing guidelines and standardized
      procedures. A multiphased, tiered-testing strategy has been proposed by numerous
      expert panels to evaluate large numbers of chemicals. In a regulatory context,
      however, a formal tiered-testing approach is not used, mostly because of the
      constraints of differing regulatory authorities and the potential cost of such a
      testing strategy. Instead, current regulatory decision making utilizes all
      available animal and human data to identify a critical adverse effect which is
      then used for setting standards. Although the current decision-making process
      does not use a formal tiered-testing approach, it appears to identify chemicals
      with neurotoxic effects. An analysis of U.S. Environmental Protection Agency
      integrated risk information system (IRIS) indicates that about 20% of the
      chemicals having standards or health advisories are based on neurotoxicity.

PMID- 9182050
TI  - Equine epidemiology: Horserace Betting Levy Board workshop. London, 24 October
      1996.

PMID- 9182049
TI  - Neurobehavioral aspects of developmental toxicity testing.
AB  - Tests for detection of neurobehavioral changes in the offspring have been a
      regulatory requirement in developmental toxicity testing of drugs for almost 20
      years. Keeping their purpose of hazard identification and risk assessment for
      humans in mind, investigators and agency reviewers have become deeply ingrained
      with some stereotyped behaviors with respect to such relevant issues as choice of
      animal species and data evaluation. Other problematic areas of study design and
      conduct, selection of litter representatives for testing, what methods to combine
      in a testing battery, and statistical treatment of results and their
      interpretation, will need more research and discussion in the future.

PMID- 9182051
TI  - [Physiologic features of the cardiovascular and respiratory systems in patients
      undergoing heart surgery under artificial circulation].

PMID- 9182052
TI  - [Maximal functional capacity of human respiratory muscles during additional
      respiratory resistance in the context of altered chemoreceptor stimulus].

PMID- 9182053
TI  - [Osmoregulatory function of the kidny under natural conditions: relationship
      between the index of osmotic concentration and reabsorption of osmotically free
      water].

PMID- 9182054
TI  - [Role of various cortical areas and their connections in the formation of spatial
      ordering in the field of brain biopotentials during postnatal ontogenesis].

PMID- 9182055
TI  - [Physiologic principles of correction of immune system function during
      inflammatory processes].

PMID- 9182056
TI  - [Sex differences in the structure of the laterality distribution in
      schoolchildren from Tuva].

PMID- 9182057
TI  - [Physiologic effects of weightlessness on man under spaceflight conditions].

PMID- 9182058
TI  - [Role of the processes of disinhibition of pacemakers in reflex activity of
      neural centers].

PMID- 9182059
TI  - [Formalized R. Rosenzweig frustration test in occupational selection of
      personnel].

PMID- 9182060
TI  - [A method for studying intellect].

PMID- 9182061
TI  - [Hormonal profile and arterial pressure in health children during puberty].

PMID- 9182062
TI  - [Cerebral organization of cognitive processes at preschool age].

PMID- 9182063
TI  - [Risky social-psychological situations as a manifestation of population psycho
      emotional stress].

PMID- 9182064
TI  - [Cross-correlations of electrical processes in the human brain during involvement
      in pathological processes in the limbic structures].

PMID- 9182065
TI  - [The regulatory role of set in the perception of verbal information].

PMID- 9182066
TI  - [Effect of the leading eye factor on EEG spectrum parameters and psychological
      indices in right-handed subjects].

PMID- 9182067
TI  - [Discrimination of spatial intervals between two lines: neurophysiologic
      substantiation of a psychophysical experiment].

PMID- 9182068
TI  - [Temporal signal processing in the visual cortex].

PMID- 9182069
TI  - [Psychophysiological features of the effect of lateralization during perception
      of a moving sound source].

PMID- 9182070
TI  - [Stress: cardiologic aspects].

PMID- 9182071
TI  - Heart rate and blood pressure variability in cardiac diseases: pharmacological
      implications.
AB  - Even at rest, blood pressure and heart fluctuate continuously around their mean
      values. Considerable interest has recently focused on the assessment of
      spontaneous in fluctuations in heart rate and blood pressure, i.e., heart rate
      and blood pressure variability, using time or frequency domain indexes. Heart
      rate variability has been extensively studied in cardiovascular disease and has
      emerged as a valuable parameter for detecting abnormalities in autonomic
      cardiovascular control, evaluating the prognosis and assessing the impact of drug
      therapy on the autonomic nervous system in patients with myocardial infarction,
      congestive heart failure or a heart transplant. In contrast, until the recent
      development of noninvasive methods for continuous blood pressure recording, blood
      pressure variability received little attention, and this parameter remains to be
      evaluated in cardiovascular disease.

PMID- 9182073
TI  - Pharmacological manipulation of human gastrointestinal blood flow.
AB  - The splanchnic circulation is one of the largest vascular regions in man. In the
      past, this has been difficult to study because of methodological problems. The
      adapting of noninvasive Doppler techniques has made it possible to develop
      reproducible measurements of coeliac and superior mesenteric artery blood flow,
      which are the main contributors to the gastrointestinal vasculature. This has
      resulted in the further understanding of neurogenic and humoral control of this
      region in a number of physiological and pathophysiological states, and has
      contributed towards the knowledge of its pharmacological control. These studies
      are of relevance to cardiovascular homeostasis and, in particular, systemic blood
      pressure control which depends upon various factors including responses in
      different vascular regions. In this review the key physiological factors which
      influence pharmacological studies on this circulation will be discussed. Examples
      will be provided, in subjects with cardiovascular and neurological disorders, of
      how administration of endogenous and exogenous substances, including drugs with
      specific pharmacological effects, alter human gastrointestinal blood flow. These
      will include insulin, alcohol, the somatostatin analogue octreotide, the central
      acting sympatholytic clonidine and the angiotensin II-converting inhibitor
      captopril. The relevance of these studies to subjects with postural hypotension
      due to sympathetic denervation and to primary hypertension, in particular, will
      be discussed.

PMID- 9182072
TI  - Thromboxane A2 and related prostaglandins in airways.
AB  - Asthma is now thought to be a chronic inflammatory disease of the airways. The
      roles of prostanoids, thromboxane A2 (TXA2) and the prostaglandins (PGs) in the
      pathogenesis and pathophysiology of asthma have fostered a wealth of studies but
      remain controversial. TXA2 and the bronchoconstrictor PGs, PGD2 and PGF2 alpha,
      are generated in greater amounts in asthmatic than in normal subjects. TXA2 is a
      potent constrictor of airway smooth muscle, an inducer of acetylcholine release
      and of airway microvascular leakage. It may participate in the thickening and the
      remodeling of the airway wall which may contribute to the airway
      hyperresponsiveness, a typical feature of asthma. Strategies for inhibition of
      TXA2 effects include antagonism of the TXA2 receptor (TP receptor) and inhibition
      of the thromboxane synthase. TP receptor antagonists could block the effects of
      all the bronchoconstrictor prostanoids because TXA2 as well as the
      bronchoconstrictor PGs act through activation of lung TP receptor. The recent
      development of specific and potent TP receptor antagonists and inhibitors of
      thromboxane synthase has provided tools to assess the role of TXA2 and broncho
      constrictor PGs in the pathophysiology of asthma.

PMID- 9182074
TI  - Antioxidant action of Vaccinium myrtillus extract on human low density
      lipoproteins in vitro: initial observations.
AB  - Oxidative modifications of low density lipoproteins (LDL) are now recognised as
      one of the major processes in atherogenesis. Various drugs, as well as a number
      of natural products, have been proposed to inhibit such processes. Among the
      naturally-occurring constituents of plants which appear to possess antioxidant
      activity are polyphenolic compounds such as flavonoids. The aqueous extract of
      Vaccinium myrtillus is rich in such molecules. In this report, we describe the in
      vitro antioxidative potential of this extract on human LDL. The copper-induced
      oxidative modification of these lipoproteins was assessed using 1) measurement of
      oxidative resistance as determined by the lag-phase preceding conjugated diene
      formation; 2) quantification of the amount of lipoperoxides and thiobarbituric
      acid-reactive substances generated, and measurement of the modification in the
      net negative electrical charge of the lipoproteins, over a 7-hour time course
      experiment. Trace amounts of V myrtillus extract (15 to 20 micrograms/mL) induce
      statistically significant changes in the oxidation behaviour of LDL, which
      include 1) prolongation of the lag-phase of conjugated diene production (P <
      0.01); 2) reduction in the formation of lipoperoxides and of thiobarbituric acid
      reactive substances up to 7 hours and especially between 1 and 5 hours (P <
      0.01); and 3) inhibition of modification in the net negative charge of LDL. These
      results demonstrate that V myrtillus extract exerts potent protective action on
      LDL particles during in vitro copper-mediated oxidation. Calculation of IC50
      values indicates that, on a molar basis, this extract may indeed be more potent
      than either ascorbic acid or butylated hydroxytoluene in the protection of LDL
      particles from oxidative stress.

PMID- 9182075
TI  - The direct effects of thyroid hormones on rat mesenteric resistance arteries.
AB  - The direct relaxant effects of thyroid hormones on mesenteric resistance vessels
      were investigated using an isometric wire myograph. Both the L- and the D-isomers
      of thyroxine (T4) and triiodothyronine (T3) were studied. In contrast with the
      long-term effects of thyroid hormones, both T4 enantiomers proved more potent in
      inducing vascular relaxation than the two T3 enantiomers. The interaction between
      thyroid hormones and calcium-induced contractions was studied. T4 concentration
      dependently inhibited the Ca2+ induced contractions, showing noncompetitive
      interaction. Furthermore, we investigated whether the endothelium was involved in
      the relaxant effect to L-T4. The T4 induced relaxation proved impaired by prior
      incubation with the nitric oxide (NO) inhibitor N-omega-nitro-L-arginine
      methylester HCl (L-NAME, 0.1 microM), indicating that T4 is able to stimulate the
      production of endothelium-derived NO. L-T4-induced relaxation was enhanced by
      prior incubation with indomethacin (10 microM), whereas in endothelium-denuded
      preparations an unaltered response was found. The present results indicate that L
      T4-induced relaxation is established by an indirect effect via the endothelium
      and by a direct effect on vascular smooth muscle cells, possibly by influencing
      calcium fluxes. Because vascular relaxation is established at supraphysiologic
      concentrations (approximately 100 times the basal level) of thyroid hormone, it
      is concluded that the direct effect of thyroid hormone on mesenteric vascular
      smooth muscle cells are not relevant for the in vivo situation.

PMID- 9182076
TI  - Inhibitory effects of okadaic acid on rat uterine contractile responses to
      different spasmogens.
AB  - In the present study, we examined the effects of okadaic acid, a selective
      inhibitor of type 1 and 2A protein phosphatases, on the mechanical responses
      evoked by oxytocin, K(+)- and Na(+)-modified solutions and ouabain in estrogen
      primed rat myometrium. Oxytocin elicited a rapid, phasic contraction followed by
      rhythmic oscillations. The phasic response was partially resistant to the absence
      of external Ca2+. Okadaic acid (1 microM) and the L-type calcium channel blocker
      nifedipine (1 microM) abolished the oscillatory component and reduced the
      initial, phasic response to about 80% of the control response. High K+ (60 mM)
      solution, ouabain (1 mM), K(+)-free medium and low Na+ (25 mM) solution induced
      extracellular Ca(2+)-dependent biphasic responses composed by an early rapid
      (KCl, ouabain and K(+)-free solution) or slower developed (25 mM Na+ solution)
      phasic contraction followed by a sustained increase in tension. Okadaic acid and
      nifedipine, alone or in combination, abolished or decreased similarly the
      contractile response evoked by these stimulants. The okadaic acid- and nifedipine
      insensitive responses to ouabain, K(+)-free and low Na+ solution were enhanced by
      increasing the extracellular concentration of Ca2+ in the medium and were
      inhibited in a dose-dependent manner by amiloride (0.05-0.5 mM). These data
      suggest that, in estrogen-primed rat uterus, dephosphorylating mechanisms by OA
      sensitive protein phosphatases play an important role in regulating myometrial
      contractions elicited by Ca2+ entry through voltage-sensitive Ca2+ channels.

PMID- 9182077
TI  - Combination of aspirin and metoclopramide produces a synergistic antithrombotic
      effect in a canine model of coronary artery thrombosis.
AB  - We compared the antithrombotic properties of low doses of aspirin (0.03, 0.1 mg
      kg-1 intravenously [iv]) and metoclopramide (0.1, 0.3 mg kg-1 iv) alone or in
      combination. The animal model chosen for this study involved the generation of
      cyclic flow variations (CFV) in the circumflex coronary artery of anaesthetized
      dogs as a result of a critical coronary stenosis associated with a controlled
      arterial lesion at the site of stenosis. Subsequent regular CFV represent
      sequential thrombus formation and embolization in the damaged vessel. Neither
      aspirin nor metoclopramide alone demonstrated antithrombotic properties at the
      doses tested. However, the combination of aspirin 0.1 mg kg-1 i.v. and
      metoclopramide 0.3 mg kg-1 i.v. produced a significant antithrombotic effect,
      reducing the frequency of large CFV from 6.7 +/- 0.5 to 0.8 +/- 0.4 cycles h-1 (P
      < 0.01) and increasing minimum mean coronary blood flow from 5.0 +/- 1.1 to 23.7
      +/- 2.6 mL min-1 (P < 0.01). This result apparently reflects an antithrombotic
      synergism between aspirin and metoclopramide since the effects of the combination
      were greater than the combined effects of the individual treatments. The
      antithrombotic influence of metoclopramide could be due to its 5HT2-antagonist or
      alpha 2-antagonist properties, both of which would inhibit platelet aggregation.
      This demonstration of a synergistic antithrombotic action of the combination of
      aspirin and metoclopramide is of interest since these two agents are often
      combined in clinical use. Its therapeutic relevance, however, remains to be
      established.

PMID- 9182078
TI  - Further biochemical characterization of imidazoline binding sites from the human
      brainstem.
AB  - Biochemical characteristics of imidazoline specific binding sites from the human
      brainstem were further investigated using [3H]idazoxan as radiolabeled ligand.
      The study of the interaction of [3H]idazoxan binding sites with heparin and
      lectins (soybean and lentil lectin) confirm the heterogeneity of these sites in
      the human brain. In fact, about 10-15% of [3H]idazoxan binding sites were
      retained by each of the three supports used, leading to the hypothesis that two
      populations of sites, with different biochemical characteristics, coexist in this
      tissue. A small proportion of [3H]idazoxan binding sites was retained on an
      affinity chromatography support consisting of a clonidine-derived Pharmalink
      column. The binding activity of these clonidine-eluted sites was markedly and
      dose-dependently improved by the addition of 'treated fall-through' fraction from
      the same column. On the other hand, this 'treated fall-through' fraction
      inhibited the binding activity detected in the solubilized human brainstem
      membranes. These results also suggest the existence of heterogeneous imidazoline
      specific binding sites in the human brainstem and the existence of endogenous
      factors able to discriminate between them.

PMID- 9182079
TI  - Oxidative degradation of cholesteryl esters in low-density lipoproteins: analysis
      by liquid chromatography-light scattering and protection by a new synthetic
      antioxidant, S20478.
AB  - Cholesteryl esters in the hydrophobic core of low-density lipoprotein (LDL)
      particles constitute a major molecular target during copper-mediated oxidation.
      To facilitate the rapid analysis and quantitation of the oxidative degradation of
      LDL cholesteryl esters, we describe a new approach based on light scattering
      detection following separation by HPLC. We have applied this approach to the
      evaluation of the protective capacity of a new synthetic antioxidant, S20478,
      during oxidation of LDL in the presence of copper ions. HPLC separation of
      cholesterol and the four major molecular species of cholesteryl esters (C16:0,
      C18:1, C18:2 and C20:4) of LDL was achieved in a single run of 20 min with high
      sensitivity (50 ng) and low background. Time course studies of the oxidative
      modification of LDL (ratio LDL protein: copper, 100 micrograms/mL: 1 microM)
      revealed that the content of unsaturated cholesteryl esters (C20:4 and C18:2)
      decreased (-30% and -15%, respectively) within 90 min of copper-mediated
      oxidation, while only minor degradation (up to 15%) of monounsaturated (C18:1)
      and saturated (C16:0) esters occurred. At 24 hours of oxidation, only traces (<
      5%) of the C20:4 and C18:2 esters were detectable; whereas 52% of the C18:1 ester
      remained (P < 0.01). Of the saturated esters, only minor proportions (35% or
      less) underwent oxidative modification. In addition, some 81% of free cholesterol
      was conserved as the native sterol. The synthetic antioxidant, S20478 (50 microM)
      was capable of inhibiting the initiation and the propagation of copper-mediated
      LDL oxidation as determined by the time- and dose-dependent inhibition of the
      formation of conjugated dienes and thiobarbituric acid-reactive substances, as
      well as the conservation of the net electrical charge of LDL; indeed S20478
      conserved cholesteryl esters in their native form up to 24 hours. However, after
      prolonged exposure to copper ions (48 hours), only 47% of the unsaturated esters
      remained (C18:2, P < 0.05). Nonetheless, S20478 (10 microM) was more efficient in
      inhibiting copper-mediated LDL oxidation as compared to probucol at the same
      concentration. These findings suggest that S20478 may be of potential interest in
      a new antioxidant approach to therapeutic stabilisation and regression of
      atherosclerotic plaques. Moreover, this method should prove useful in the
      assessment of the integrity of native LDL, and provides a new chemical marker of
      the degree of LDL oxidation.

PMID- 9182080
TI  - Effects of K+ channel inhibitors and antagonists on NS-004 evoked relaxations in
      guinea-pig isolated trachea.
AB  - The smooth muscle relaxant responses to NS-004, an activator of charybdotoxin
      sensitive, large conductance Ca(2+)-dependent K+ channels (BKCa) were studied on
      the basal spontaneous tone in guinea-pig trachea in vitro. The sensitivity of
      these responses to a range of K+ channel inhibitors and antagonists were also
      evaluated. NS-004 (0.1-30 microM) evoked concentration-related relaxations (pIC50
      5.48 +/- 0.13) on the spontaneous tone in guinea-pig tracheal rings, suspended in
      Krebs bicarbonate solution, with a maximum response not different to that to
      aminophylline (1 microM). Charybdotoxin (0.03 and 0.1 microM) or iberiotoxin (0.1
      microM) significantly displaced the NS-004 concentration-response curve to the
      right of control with no change in maximum response. In contrast, glibenclamide
      (1.0 microM) apamin (0.1 microM) and dofetilide (1.0 microM) each failed to
      modify the responses to NS-004 on spontaneous tone in guinea-pig trachea. These
      results suggest that relaxations in guinea-pig tracheal smooth muscle to the
      substituted benzimidazolone, NS-004, involve the activation of BKCa channels.

PMID- 9182081
TI  - Hemodynamic and neurohormonal effects of flosequinan in patients with heart
      failure.
AB  - In a double-blind, placebo-controlled study, the central and peripheral
      hemodynamic effects of 100 mg oral flosequinan and the impact of this drug on
      neurohormonal activation were noninvasively evaluated in 18 patients with
      congestive heart failure, after the first administration and after 10 days of
      treatment. No significant hemodynamic and neurohormonal changes were observed
      after acute administration. After 10 days, flosequinan produced central and
      peripheral hemodynamic improvement characterized by an increase in left
      ventricular circumferential fiber shortening velocity (+12%), a decrease in total
      systemic resistance (-36%), and an increase in leg blood flow (+37%). No
      significant changes were observed in heart rate and arterial pressure in patients
      receiving flosequinan, though a slight increase in heart rate (+17%) was
      recorded. Despite these favorable hemodynamic effects, flosequinan significantly
      increased plasma norepinephrine (+38%) and plasma renin activity (+13%) after 10
      days of treatment. Thus, the beneficial central and peripheral hemodynamic
      effects of flosequinan are accompanied by activation of the sympathetic and
      reninangiotensin systems. This might be related to the unfavorable effects of the
      drug on survival in patients with heart failure.

PMID- 9182083
TI  - Exercise and Immunology: Practical Applications. 2nd Symposium of the
      International Society of Exercise and Immunology. Brussels, November 17-18, 1995.
      Proceedings and abstracts.

PMID- 9182082
TI  - Pharmacokinetics and pharmacodynamics of two oral forms of cefuroxime axetil.
AB  - Cefuroxime axetil is a cefuroxime ester that can be administered by mouth. Two
      dosage forms (tablets and granules) have been developed for oral administration.
      We evaluated the pharmacokinetics and pharmacodynamics of these forms in an open
      cross-over study involving 12 healthy volunteers receiving single doses of 250
      mg. The bioavailability of the two forms was different, the observed peak
      concentration and time-concentration curve values of the tablet form being,
      respectively, 39 and 27% higher than those of the granule form. However, ex vivo
      studies of serum bactericidal activity against Streptococcus pneumoniae showed no
      significant differences between the two formulations. This is in keeping with the
      fact that the bactericidal activity of samples from only six subjects gave
      evaluable data for Haemophilus influenzae; although small differences were found
      between the two formulations, further investigations are required. The
      pharmacodynamic approach is becoming an essential element in determining the
      equivalence of antibiotic dosage forms.

PMID- 9182084
TI  - [Idiopathic eosinophilia].
AB  - Peripheral and tissue eosinophilia are associated with a wide variety of
      inflammatory syndromes. These include both multisystem and limited diseases with
      vasculitis or non-vasculitic tissue damage and variable expression of end-stage
      fibrosis. The idiopathic hypereosinophilic syndrome (IHS) represents a
      multisystem disorder defined by sustained eosinophilia of an undetectable cause
      with significant organ system dysfunction. Although not specified as such in the
      criteria for the diagnosis of IHS, there are idiopathic eosinophilic syndromes
      that are clinically distinct from IHS by virtue of the fact that the eosinophilic
      inflammation is limited to specific tissues (such as the skin) with an overall
      good prognosis. The pathogenic role of the eosinophilic granulocyte in these
      conditions is attested by evidence of eosinophil activation and degranulation at
      sites of tissue injury. The recruitment and localization of eosinophils to
      specific sites of tissue inflammation involves cytokines with haematopoietic
      growth factor activity, adhesion molecules expressed both by the vascular
      endothelium and eosinophils, and chemoattractants that stimulate eosinophil
      migration. Recently, overexpression of IL-5 in transgenic mice was shown to lead
      to both peripheral blood eosinophilia and tissue eosinophilia. With the advances
      in our understanding of cytokine-dependent regulatory mechanisms that control the
      peripheral eosinophil number as well as the recruitment and survivability of
      eosinophils at sites of inflammation, more targeted ways of manipulating the
      eosinophil reaction can be expected in the future.

PMID- 9182085
TI  - [Cell cycle control, genetic instability and cancer].
AB  - During the past years the elucidation of cell cycle regulation has revolutionized
      our understanding of cancer development. Many new genes have been identified
      which promote genetic instability when mutated. They encode cyclins, inhibitors
      of cyclin-dependent kinases (CDKs) or other cell cycle regulators. The regulation
      of the CDK activities in different phases of the cell cycle controls the correct
      process of DNA synthesis and replication. Complex signal transduction systems, so
      called checkpoints, regulate growth arrest, DNA repair and programmed cell death
      (apoptosis) and thereby prevent the formation of tumour cells. An overview is
      presented on the molecular mechanisms of cell cycle control and their
      significance for genetic stability. The functions of proto-oncogenes (e.g., c
      myc) and tumour-suppressor genes (e.g., p53) in this context is described. In
      particular, recent advances in the understanding of skin carcinogenesis, the role
      of UV radiation and cancer therapy are discussed.

PMID- 9182086
TI  - [Health consciousness and risk behavior of prostitutes].
AB  - Regular examinations of prostitutes may reduce the incidence of sexually
      transmitted diseases in this high risk group. Therefore since April 1988 regular
      mandatory examinations have been offered by the regional health office in
      cooperation with the Department of Dermatology of the Ruhr-University of Bochum.
      The aim of this study was to evaluate the acceptance and efficiency of such an
      examination. The study was based on anonymous questionnaires. Mean age of the 80
      prostitutes was 31.4; 67 of then were born in Germany. 78 of the women always
      used condoms, while 71 thought that condoms prevent STDs. Three women suffered
      from a STD in the last 12 months. The majority the women (75 from this 80
      prostitutes) did not perceive the examination as discrimination, while 71 felt
      the examinations were of high quality. These results indicate that regular
      mandatory examinations should be part of health prevention care of prostitutes
      and that they are well accepted and tolerated by these women.

PMID- 9182087
TI  - [Metastatic melanoma of low Breslow thickness].
AB  - We treated 8123 patients with invasive malignant melanoma were treated up to
      1995. 2200 had invasive melanomas with less than 0.75 mm Breslow thickness; of
      these, 45 developed metastases. Three had second primary tumors with greater
      thickness. One case showed metastasis from another tumor. In two cases the
      metastases were not ascertained histologically. The remaining 39 cases showed
      some peculiarities: a greater proportion of late and of internal (as contrasted
      to regional) metastases. Most of these primary tumors had a Breslow thickness of
      more than 0.5 mm and were Clark level III or even IV. Male patients and primary
      tumor sites in the area of head and neck were significantly over-represented.

PMID- 9182088
TI  - [Diagnosis of dermatomycoses with polymerase chain reaction].
AB  - A polymerase chain reaction (PCR) assay for the detection of dermatophytes was
      established. The primers "TR1" and "TR2" amplify a 581 bp fragment within the
      gene coding for the small ribosomal subunit (185 rRNA) of fungi. PCR allowed the
      detection of isolates of 7 common dermatophytes and in addition several yeasts
      and moulds. Hybridisation with specific oligonucleotides results in the
      identification of dermatophytes and Candida albicans. Restriction analysis of the
      PCR product allowed us to distinguish between dermatophytes and yeasts or moulds.
      The specificity of the PCR with respect to fungi was assessed by testing human
      DNA collected from 42 dermis and epidermis specimens as well as DNA from selected
      plants and animals. To evaluate the clinical relevance of the PCR assay, 69
      routinely collected skin and nail specimens were examined by PCR and culture. PCR
      detected dermatophytes in 35 and culture in 28 of 38 specimens that were
      classified as positive. Sensitivity of PCR (92%) was higher than that of culture
      (73%). These results show that PCR has advantages over culture for the detection
      of dermatophytes.

PMID- 9182089
TI  - [Reticular lentigo].
AB  - We studied the clinical and histopathologic features in five patients with
      reticulated lentigo. This peculiar pigmented skin lesions has previously been
      described under the designations "acquired reticulated lentigo", ink spot
      lentigo, "reticulated melanotic macule" or "reticulated lentigo". Each of the 4
      males and 1 females in our study (age range: 16 to 57 years; mean age: 34 years)
      had a single, 4-6 mm large, black macule with irregular, fingerlike extensions at
      the periphery. All lesions were situated on the upper back and surrounded by
      numerous sun-induced freckles. Dermatoscopic examination revealed irregularly
      formed "meshes" and confirmed the reticulated pattern seen clinically.
      Reticulated lentigo presented mostly in individuals with skin type 1, red to
      blond hair, and blue eyes. The clinical diagnosis in 4 out of 5 cases was
      melanoma in situ. Histopathologically, reticulated lentigo was mainly
      characterized by a sharply circumscribed hyperpigmentation of the lower epidermis
      with accentuation at the tips of elongated and clubbed rete ridges. In addition,
      a normal or slightly increased melanocyte number in the basal layer and an
      infiltrate of melanophages in the upper dermis was noted. Reticulated lentigo
      shows histopathologic features similar to those of melanotic macules on volar
      skin and mucous membranes. Because of its characteristic clinical, dermatoscopic
      and histopathologic features reticulated lentigo can be regarded as a distinctive
      clinicopathologic entity.

PMID- 9182090
TI  - [SAPHO syndrome. Case description of 3 patients with acne conglobata and
      osteoarticular symptoms].
AB  - We report three new cases of the SAPHO syndrome. This acronyme consists of
      synovitis, acne, pustulosis, hyperostosis and osteitis. Symptoms of this
      syndrome, which may not all be present, are pustulotic skin diseases (pustulosis
      palmoplantaris or severe acne) associated with osteoarticular lesions (mainly
      sternoclavicular hyperostosis, spondylarthropathies or chronic recurrent
      multifocal osteomyelitis). The dermatological aspects of this syndrome are
      discussed in detail.

PMID- 9182091
TI  - [Pseudoxanthoma elasticum. Skin changes as a marker of systemic illness].
AB  - Angioid streaks were diagnosed in a 42-year-old woman. Since age 20 she had
      developed circumscribed atrophic yellow-grey lesions on her neck, axillae and
      other flexural sites. In spite of highly characteristic skin changes, the
      diagnosis of pseudoxanthoma elasticum was first confirmed by a biopsy from
      lesional skin 22 years after the disease onset. Based on the present case and an
      analysis of the recent literature, the findings characteristic for pseudoxanthoma
      elasticum in the skin, eyes and cardiovascular system are delineated, the
      differential diagnosis of the skin lesions, as well as the pathogenesis and the
      prognosis are discussed, and the new classification of pseudoxanthoma elasticum,
      based on major and minor criteria, is described.

PMID- 9182092
TI  - [Lung edema and erosive gastroduodenitis as a sequela of inappropriate use of an
      adrenaline dose aerosol after wasp sting].
AB  - Epinephrine (adrenaline) is an important drug in the treatment of severe
      anaphylactic reactions. Along with other drugs such as H1-antihistamines and
      glucocorticosteroids, it is found in every first aid kit for at-risk individuals,
      such as those who are allergic to insect stings. Subcutaneous or intramuscular
      injections if carried out by an untrained individual or the patient himself might
      give rise to potential problems. Therefore, it is common to prescribe epinephrine
      pressure aerosol as a safer alternative. If epinephrine aerosol is overused, it
      can cause serious problems. A patient developed by self-medication following a
      wasp sting lung edema as well as an erosive gastroduodenitis. She consumed two
      aerosol vials each of which contained about 73 mg of adrenaline. In order to
      avoid such incidents it is crucial that every doctor provides his or her patient
      with sufficient oral and written information regarding the correct use fo
      epinephrine inhalers.

PMID- 9182093
TI  - [Perianal ergotismus gangraenosus].
AB  - Ergotamine-containing drugs are widely used in the treatment of acute migraine
      attacks. Among others, spastic vasoconstrictions are one of the possible side
      effects usually affecting the lower extremities and sometimes leading to
      gangrene. The case of a 75 year old woman is presented who was suffering from
      migraine-attacks since adolescence. Due to longterm use of ergotamine containing
      suppositories she developed perianal ulcers. After withdrawal of the drug the
      ulcers healed up entirely. The spectrum of ergotamine-induced side-effects and
      possible intervention strategies are discussed.

PMID- 9182094
TI  - [Allergy-inducing potency of tea tree oil].

PMID- 9182095
TI  - [Sexually transmitted diseases in HIV infection].

PMID- 9182096
TI  - The best studies do one thing well.

PMID- 9182097
TI  - Clinical rationale for topical antimicrobial preparations.

PMID- 9182098
TI  - Antiviral resistance: mechanisms, clinical significance, and future implications.
AB  - The increased awareness of antiviral resistance over the past decade has
      paralleled the development of new antiviral agents. While such resistant viral
      isolates are of clinical significance primarily in immunocompromised individuals,
      the development and transmission of such mutants have been reported in
      immunocompetent persons as well. As antiviral agents are increasingly utilised by
      the clinician, the incidence of such occurrences is likely to increase. Issues
      relating to mechanisms of antiviral resistance, clinical manifestations and
      significance of resistance, and implications for future antiviral development and
      utilisation are reviewed in this article. Viruses that are discussed include
      herpes simplex virus, varicella-zoster virus, cytomegalovirus, influenza A virus,
      and human immunodeficiency virus.

PMID- 9182099
TI  - Enzyme kinetics and biochemical analysis of ImiS, the metallo-beta-lactamase from
      Aeromonas sobria 163a.
AB  - The metallo-beta-lactamase from Aeromonas sobria 163a, ImiS, was isolated in a
      two stage purification procedure using protein affinity columns. Enzyme kinetics
      show that ImiS hydrolyses the carbapenems but displays poor activity against
      other beta-lactams. ImiS possesses the narrowest spectrum of activity of the
      Group 3 enzymes that have been analysed. Sequencing of the 40 N-terminal amino
      acids show this region to be identical to that of the CphA metallo-beta-lactamase
      from Aeromonas hydrophila (Massidda, Rossolini & Satta, 1991). Light scattering
      analysis indicates that ImiS is functionally active as a monomer.

PMID- 9182100
TI  - Imipenem and cephem resistant Pseudomonas aeruginosa carrying plasmids coding for
      class B beta-lactamase.
AB  - From October 1988 to January 1992, nine isolates of Pseudomonas aeruginosa
      carrying transferable plasmids encoding imipenem-hydrolyzing beta-lactamase (pI =
      c. 9.5) were recovered from nine different patients in a neurosurgical ward of a
      hospital in Japan. The beta-lactamase activities of the sonicated extracts from
      the transconjugants were inhibited by EDTA and this was partially reversible by
      the addition of zinc cation. The substrate specificity and pI of the beta
      lactamase were similar to those of the metallo beta-lactamases from P. aeruginosa
      and Serratia marcescens TN9106. All strains were resistant to imipenem,
      carbenicillin and antipseudomonal cephems including ceftazidime, cefsulodin,
      cefpirome, while four and five strains were susceptible to piperacillin and
      aztreonam, respectively. Both low level imipenem resistance and high level cephem
      resistance were co-transferred with the production of metallo beta-lactamase,
      while resistance to piperacillin, aztreonam, and high level imipenem-resistance
      were not selected. Production of chromosomal cephalosporinase in piperacillin
      resistant strains was derepressed, and production of outer membrane protein of D2
      was diminished in highly imipenem resistant strains. Six strains were isolated in
      1991, and the amounts of antipseudomonal agents, especially imipenem, used in the
      neurosurgical ward increased markedly in this year. Only three of the nine
      isolates had the same serotype, pyocin type and phage type. Our results suggest
      that the repeated isolation of imipenem and cephem-resistant P. aeruginosa
      producing metallo beta-lactamase was related to the high usage of antipseudomonal
      beta-lactam antibiotics such as imipenem, and was exacerbated by the
      dissemination of a plasmid.

PMID- 9182101
TI  - Identification of mecA-related oxacillin resistance in staphylococci by the E
      test and the broth microdilution method.
AB  - A set of 165 strains of different staphylococcal species, 67 Staphylococcus
      aureus, 71 novobiocin-sensitive coagulase-negative staphylococci (CNS) and 27
      novobiocin-resistant CNS was used. The oxacillin and methicillin MICs were
      recorded after 24 and 42 h of incubation at 35 degrees C and at 30 degrees C.
      Significantly higher MICs were recorded at 30 degrees C compared with 35 degrees
      C. While a poor discrimination between mecA-positive and mecA-negative strains
      was obtained with methicillin, the oxacillin MICs enabled identification of
      resistant strains under certain conditions. The distribution of MICs differed
      between the three groups of species. Separation of uninduced mecA-positive (> or
      = 4.0 mg oxacillin/L) and mecA-negative (< or = 2.0 mg oxacillin/L) strains of S.
      aureus was only achieved with the E test and after 42 h of incubation. Oxacillin
      induction yielded higher MICs for mecA-positive strains of S. aureus, and a
      separation from mecA-negative strains was achieved with the E test after 24 h and
      with the broth microdilution method after 42 h. Separation of mecA-positive and
      mecA-negative strains of novobiocin-sensitive CNS required agar supplemented with
      5% blood, incubation of MIC trays and E test for 42 h, and species-specific
      oxacillin MIC breakpoints (S < or = 0.5 mg/L and R > or = 1.0 mg/L). The mecA
      positive and mecA-negative strains of novobiocin-resistant CNS were clearly
      separated after 24 h of incubation by either method.

PMID- 9182102
TI  - Mobile rRNA methylase genes coding for erythromycin resistance in Actinobacillus
      actinomycetemcomitans.
AB  - We found that 17 (68%) of 25 Actinobacillus actinomycetemcomitans isolated from
      periodontally diseased sites had MICs of erythromycin > or = 8 mg/L. The isolates
      were hybridized with five rRNA methylase genes and gene mobility was determined.
      Twenty-four (96%) of 25 isolates hybridized with one or more rRNA methylase
      genes. Representative isolates were able to transfer erythromycin resistance to
      Haemophilus influenzae and Enterococcus faecalis recipients. The transconjugants
      were shown to carry rRNA methylase genes by DNA probe hybridization and had MICs
      of erythromycin 32 to 256 mg/L.

PMID- 9182103
TI  - Rapid high performance liquid chromatographic assay for antifungal agents in
      human sera.
AB  - Serum concentration of seven antifungal agents, amphotericin B, 5-flucytosine,
      ketoconazole, fluconazole, itraconazole, miconazole and econazole were assayed
      using a single step sample preparation and an isocratic High Performance Liquid
      Chromatography (HPLC) procedure based on three mobile phases of similar
      components. Our method was simple, flexible and rapid, the assays being completed
      within half an hour. The method showed high reproducibility, good sensitivity
      with detection limits of 0.078 to 0.625 mg/L except for miconazole and econazole,
      and high recovery rates of 86-l05%. Out of 24 therapeutic agents tested only
      aztreonam and trimethoprim were found to interfere with the assay of 5
      flucytosine and fluconazole respectively, using this protocol. HPLC assay should
      be useful in the clinical laboratory for monitoring patients on antifungal
      therapy.

PMID- 9182104
TI  - Clarithromycin resistance in Helicobacter pylori: prevalence in untreated
      dyspeptic patients and stability in vitro.
AB  - Susceptibilities to clarithromycin and metronidazole of 444 Helicobacter pylori
      isolates cultured from antral biopsies of 444 dyspeptic patients were determined
      by disc diffusion tests (15 mu g disc for clarithromycin, 5 mu g disc for
      metronidazole). Susceptibility of 46 of these isolates to erythromycin (5 mu g
      disc) was also tested. Minimal inhibitory concentrations (MICs) of clarithromycin
      for 42 selected isolates were determined by a plate dilution method. A zone
      diameter of 30 mm was defined as a 'cut-off' size differentiating susceptibility
      and resistance of the organism to clarithromycin, by comparing results obtained
      with the two methods. Of the 444 isolates, 424 (95.5%) were highly sensitive to
      clarithromycin, with zone diameters ranging from 30 to 98 mm. Twenty isolates
      (4.5%) were defined as resistant to clarithromycin, with zone diameters ranging
      between 6 and 28 mm. The incidence of clarithromycin resistance was similar in
      men and women and in different age groups, and was not significantly different
      between patients with peptic ulcer and non-ulcer dyspepsia. Among the 444
      isolates, 168 (37.8%) were metronidazole resistant. There was cross resistance
      between clarithromycin and erythromycin, but not between clarithromycin and
      metronidazole. Stability of clarithromycin resistance was evaluated by the disc
      diffusion test and confirmed by the plate dilution method. Among the 20
      clarithromycin-resistant isolates, nine (45%) reverted to be sensitive after 25
      subcultures on drug-free agar. The findings in this study indicate that the
      incidence of clarithromycin-resistant H. pylori in untreated dyspeptic patients
      is low. Cross-resistance occurs between macrolides and resistance to
      clarithromycin in some strains is reversible.

PMID- 9182105
TI  - In-vitro activity of azithromycin in against intracellular Helicobacter pylori.
AB  - We studied the effect in vitro of azithromycin on the clinical strain
      Helicobacter pylori H:72 growing intracellularly in monolayers of HEp-2
      epithelial cells. After using gentamicin to eradicate extracellular bacteria,
      different concentrations of azithromycin were added to the infected cells and
      samples were taken after 0, 4, 8 and 24 h. Infected cells not exposed to
      antibiotic were included as controls. The MIC of azithromycin to the H. pylori
      was 0.25 mg/L and the MBC 0.5 mg/L in a broth dilution plate count method. A
      bactericidal effect was observed on intracellular H. pylori, with inhibition
      increasing with increasing azithromycin concentrations. However, extracellular
      concentrations of 200 x MBC were necessary to achieve intracellular killing. Our
      results show that azithromycin is active against intracellular H. pylori
      suggesting that it might be possible to exploit this activity when treating
      infections due to the organism.

PMID- 9182106
TI  - Comparison of the activity of fluoroquinolones against Mycobacterium avium in
      cell-free systems and a human monocyte in-vitro infection model.
AB  - Mycobacterium avium frequently causes disseminated infection in advanced AIDS.
      Some quinolones including ciprofloxacin and sparfloxacin have anti-M. avium
      activity in cell-free systems in vitro. Acidic conditions within macrophages and
      variable intracellular drug penetration and compartmentalization may, however,
      alter the susceptibility of M. avium to these antimicrobial agents in human
      tissues. We, therefore, tested the activities of 47 quinolones against M. avium
      in a human monocyte infection model using ciprofloxacin susceptible (MIC = 0.25
      mg/L) and resistant (MIC = 4 mg/L) patient isolates. Monocytes from healthy
      subjects were infected with M. avium and cultured with or without antimicrobials
      for 8 days. Some quinolones had poor activity against M. avium in the monocyte
      culture system despite low MICs (< or = 0.25 mg/L); in contrast, some quinolones
      with MICs > 32 mg/L showed some inhibition of M. avium growth within monocytes at
      4 mg/L. Six quinolones synthesized based on structure-activity analysis were more
      active than ciprofloxacin. These data underscore the importance of evaluating
      drug activity of new antimicrobial agents against intracellular pathogens in a
      macrophage model as well as in cell-free systems.

PMID- 9182107
TI  - Activity of rifabutin, clarithromycin, ethambutol, sparfloxacin and amikacin,
      alone and in combination, against Mycobacterium avium complex in human
      macrophages.
AB  - Disseminated infection with Microbacterium avium complex (MAC) in patients with
      AIDS is currently treated with a combination of antimycobacterial agents in order
      to prevent the selection of resistant mutant strains. Although clinical and
      microbiological responses can generally be achieved within a few weeks, relapses
      are common and require modification of the combination regimen or identification
      of effective alternate therapies. In this study we investigated the activities of
      rifabutin 0.5 mg/L, sparfloxacin 1 mg/L, clarithromycin 4 mg/L, amikacin 16 mg/L
      and ethambutol 2 mg/L, alone and in combination, against nine strains of M. avium
      isolated from the blood of patients with AIDS in order to identify regimens with
      the greatest therapeutic potential. Macrophages derived from human monocytes were
      infected with M. avium and inoculated with a single drug or a combination of
      drugs; cfu counts were performed at 0, 4 and 7 days after infection. At day 4 and
      at day 7, the combination of rifabutin, clarithromycin, amikacin and sparfloxacin
      displayed the highest degree of activity. However, the activity did not differ
      significantly from that of the combination of rifabutin, clarithromycin and
      ethambutol. The results of this study confirm the activity of combinations
      including rifabutin and clarithromycin (+/- ethambutol) in human monocyte-derived
      macrophages and suggest potentially useful associations in incorporating
      sparfloxacin and amikacin.

PMID- 9182108
TI  - Activity of pyronaridine and mepacrine against twelve strains of Plasmodium
      falciparum in vitro.
AB  - Pyronaridine, an acridine derivative, has been found effective in China for the
      treatment of drug-resistant falciparum malaria. The activities of pyronaridine
      and mepacrine were compared with those of standard antimalarial drugs in vitro
      against chloroquine-sensitive (CS) and chloroquine-resistant (CR) Plasmodium
      falciparum isolates to investigate cross resistance. The 50% inhibitory
      concentrations (IC(50)) against the resistant isolates were 2.8-fold higher than
      the sensitive isolates for pyronaridine (CS = 7.3 nM; CR = 20.5 nM) and 3.2-fold
      higher for mepacrine (CS = 13.3 nM; CR = 42.6 nM). These same isolates showed an
      11-fold difference in sensitivity to chloroquine with mean IC(50) values of 21 nM
      for sensitive and 239 nM for resistant parasites. A significant correlation was
      observed between parasite sensitivity (IC(50)) to pyronaridine and the drugs,
      mepacrine, amodiaquine and chloroquine. However, the high level of activity seen
      with pyronaridine, even against the CR isolates, should encourage further field
      trials with this drug.

PMID- 9182109
TI  - Comparative internalization and recycling of different amphotericin B
      formulations by a macrophage-like cell line.
AB  - The amount of amphotericin B (AmB) associated with cultured murine macrophage
      like J774 cells, after incubation with various AmB lipid formulations, was
      determined by absorption spectroscopy. Large, negatively charged, AmB-containing,
      multilamellar vesicles and small cholesteryl sulphate-AmB complexes both enhanced
      the amount of AmB associated with J774 cells at 37 degrees C (up to 500-fold the
      extracellular concentration). In contrast, AmB-containing, small, negatively
      charged vesicles (AmBisome), positively charged, oligolamellar vesicles and mixed
      micelles showed a lower association of the antibiotic with cells, compared with
      AmB added from a solution in dimethylsulphoxide or Fungizone. Experiments
      performed at 40 degrees C showed a large reduction of AmB uptake for AmB
      preparations and AmB added from a solution in dimethysulphoxide or Fungizone,
      suggesting a high percentage of internalization of the antibiotic. Experiments in
      the presence of cytochalasin B resulted in a decrease of AmB uptake mainly for
      the preparations of large diameter, suggesting that these formulations were taken
      up by phagocytosis. A comparative study with Chinese hamster ovary cells, a model
      of non-phagocytic cells, showed a reduction in the take up of AmB. This reduction
      was always more marked when AmB was incorporated in lipid formulations. On the
      other hand, accumulation of the antibiotic in J774 cells was shown to be followed
      by its release from the cells in an unbound form, the extent of release depending
      on the type of vector used. The results suggest that in some cases macrophages
      can be considered as reservoirs of antibiotic, releasing free AmB in the medium.

PMID- 9182110
TI  - HIV-induced cytopathology and viral load in a pentamidine-treated lymphocytic
      cell line.
AB  - Preincubation of CD4 lymphocytes with pentamidine isethionate at a concentration
      of 1.5 mg/L then removal from incubation medium prior to addition of HIV-1, or
      incubation of cells with the drug and virus simultaneously, increased HIV-1 DNA
      load but reduced p24 antigen release. The number of syncytia generated was not
      affected by the presence of pentamidine. The extent of balloon degeneration of
      cells was greater, however, although this was not associated with a discernable
      increase in cellular necrosis or reduction in cell viability. This suggests that
      drug-treatment resulted in an increased load of intracytoplasmic (but not
      necessarily integrated) forms of HIV- 1; this may explain the lower levels of
      antigen produced and also the balloon degeneration of treated cells, a phenomenon
      previously observed with other retroviruses.

PMID- 9182111
TI  - Pharmacokinetics of a single dose of teicoplanin in burn patients.
AB  - Patients with severe burns are susceptible to infection with Gram-positive
      organisms including methicillin-resistant Staphylococcus aureus, and often
      require higher antibiotic dosages compared with other patients. This study
      examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15
      adults and five children with severe burns. Adults were aged 21-82 years with a
      median total body surface area (TBSA) burn of 30% (range 15-60%). Children were
      aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the
      median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and
      7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding
      values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three
      compartment model, the median terminal half life in adults was 114 h (47-278 h).
      Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41
      h). The median concentration of teicoplanin in fluid from the burn wound was 60%
      of the serum antibiotic concentration. A single iv dose of 12 mg/kg of
      teicoplanin was sufficient to produce therapeutic serum concentrations in burn
      patients for 24 h, but monitoring of antibiotic levels in serum may be advisable
      in those with high total clearance, especially children.

PMID- 9182112
TI  - Comparison of oral cefuroxime axetil and oral amoxycillin/clavulanate in the
      treatment of community-acquired pneumonia.
AB  - Cefuroxime axetil has been evaluated previously in the treatment of lower
      respiratory tract infections, but not specifically in the treatment of community
      acquired pneumonia. In a multicentre, investigator-blinded clinical trial, 162
      patients with community-acquired pneumonia were randomly assigned to receive
      orally either cefuroxime axetil 500 mg bid (n = 84) or amoxycillin/clavulanate
      500 mg/125 mg tid (n = 78) for 10 days. Organisms were isolated from the
      pretreatment sputum specimens of 97 of 162 (60%) patients, the commonest isolates
      being Streptococcus pneumoniae (38%) and Haemophilus influenzae (18%). A
      satisfactory clinical outcome (cure or improvement) was achieved in 100% (55 of
      55) and 96% (49 of 51) of the clinically evaluable patients treated with
      cefuroxime axetil or amoxycillin/clavulanate, respectively (P = 0.23). With
      respect to eradication of bacterial pathogens, a satisfactory outcome (cure,
      presumed cure or cure with colonization) was obtained in 94% (32 of 34) and 93%
      (37 of 40) of bacteriologically evaluable patients treated with cefuroxime axetil
      or amoxycillin/clavulanate, respectively (P = 1.00). Both treatment regimens used
      in this study were well tolerated. The most common drug-related adverse
      experiences were gastrointestinal events, reported by 8% and 4%, respectively, of
      the patients in the amoxycillin/clavulanate and cefuroxime axetil groups, a
      difference which was not statistically significant (P = 0.32). These results
      indicate that cefuroxime axetil twice a day is as effective as
      amoxycillin/clavulanate three times a day in the treatment of outpatients with
      mild to moderate community-acquired pneumonia.

PMID- 9182113
TI  - Cefpodoxime proxetil suspension compared with cefaclor suspension for treatment
      of acute otitis media in paediatric patients.
AB  - A multicentre open-label, randomised trial was performed to compare the efficacy
      and safety of cefpodoxime proxetil bd and cefaclor tds in the treatment of acute
      otitis media in children. A total of 167 children aged from 1 month to 11 years
      were enrolled in five centres: 78 treated with cefpodoxime and 83 treated with
      cefaclor, were evaluated in the ITT analysis. After tympanocentesis and culture
      of middle ear fluid, a pathogen was isolated from 85 (53%) of the 161 evaluable
      patients for the ITT analysis. The organisms isolated were as follows:
      Streptococcus pneumoniae: (n = 33, 37.5%); Haemophilus influenzae: (n = 22, 25%);
      Staphylococcus aureus: (n = 15, 17.1%); Streptococcus pyogenes: (n = 8, 9.1%);
      Moraxella catarrhalis: (n = 2, 2.3%); others (n = 6, 6.8%). Success (defined as a
      satisfactory clinical outcome, either cure or improvement) was achieved at the
      end of treatment, in 93.6% of ther patients in the cefpodoxime group and 91.6% of
      the patients in the cefaclor group (P> 0.05). Clinical recurrence was identified
      at the follow-up visit (30 days after inclusion), in 6.4% of the cefpodoxime
      treated patients and 7.2% of the cefaclor-treated patients (P> 0.05). The drugs
      were well tolerated by 78/79 (99%) of patients in the cefpodoxime-treated group
      and 80/85 (94%) in the cefaclor-treated group. The incidence of adverse effects
      was higher in the cefaclor group than in the cefpodoxime group, but this was not
      statistically significant (P > 0.05). IN conclusion, cefpodaxime proxetil
      administered bd is as effective as cefaclor administered tds in the treatment of
      acute otitis media in children. The less frequent dosing schedule of cefpodoxime
      (bd) compared with cefaclor (tds) appears to be more convenient for the treatment
      of the infections in children.

PMID- 9182114
TI  - Efficacy of norfloxacin and doxycycline for treatment of vibrio cholerae 0139
      infection.
AB  - An open randomised controlled clinical trial with 160 adults with acute watery
      diarrhoea and severe dehydration compared the efficacy of varying regimens of
      norfloxacin and doxycycline for the treatment of cholera caused by Vibrio
      cholerae 0139 Bengal. Data were analysed for the 111 patients who were faeces
      culture positive for V. cholerae 0139. In addition to rehydration therapy, 28
      patients received 300 mg of doxycycline as a single dose on admission, 26
      patients received norfloxacin 400 mg bd for three days, 28 patients received a
      single dose of 800 mg of norfloxacin and 29 patients received no antibiotic
      (control group). Patients in the three treatment groups and control group had
      comparable characteristics on admission. All three treatment groups had reduced
      stool output, duration of diarrhoea and fluid intake compared with the control
      group. Multidose norfloxacin treatment significantly reduced stool output,
      duration of diarrhoea and fluid requirement compared with the other regimens.

PMID- 9182115
TI  - Multiple dose netivudine, a potent anti-varicella zoster virus agent, in healthy
      elderly volunteers and patients with shingles.
AB  - Netivudine is a nucleoside analogue with potent anti-varicella zoster virus
      activity. We now report two open studies of the pharmacokinetics and tolerability
      of netivudine in doses of 50, 100 and 200 mg twice daily. In one study, healthy
      volunteers received an initial, single dose followed, a week later, by repeat
      dosing for 9 1/2 days; in the other, patients with shingles were treated for 8
      days and data were also recorded for rash resolution and pain duration and
      intensity. Netivudine was well tolerated in both studies. Plasma concentrations
      were similar in patients and healthy volunteers and increased in proportion to
      dose. Steady state concentrations were 15-25% lower than expected from single
      dose data, probably because of slightly decreased netivudine absorption after
      food. Elimination half-life was l4-20 h. Plasma concentrations of 5
      propynyluracil (5-PU), the main metabolite of netivudine, did not increase in
      proportion to the netivudine dose and tended to be higher in patients than
      volunteers. 5-PU concentrations remained elevated for up to 72 h after the last
      netivudine dose, suggesting continued but slow release from unabsorbed netivudine
      in the gut lumen. New lesion formation ceased and vesicles crusted most quickly
      in the 200 mg group; zoster-associated pain intensity, was reduced in a dose
      related manner.

PMID- 9182116
TI  - Effects of synthetic form of tracheal antimicrobial peptide on respiratory
      pathogens.
AB  - We have synthesized a C-terminal portion of tracheal antimicrobial peptide (TAP)
      with 38 amino acids and tested it for efficacy on various clinical isolates of
      Pseudomonas aeruginosa strains from patients with cystic fibrosis and also on
      Aspergillus fumigatus. Our results indicate that the synthetic TAP has both
      potent bactericidal and fungicidal activities and that a combination of TAP and
      amphotericin B showed strong additive effects of growth inhibition on A
      fumigatus. These results suggest that TAP is potentially an effective therapy for
      Aspergillus and multi-drug-resistant Pseudomonas, pathogens that are often a
      serious threat to patients with cystic fibrosis.

PMID- 9182117
TI  - Penicillin-binding protein 5 as an inhibitory target of cefozopran in
      Enterococcus faecalis.
AB  - The concentration of cefozopran which inhibits binding of [14C]benzylpenicillin
      to penicillin-binding protein (PBP) 5 of Enterococcus faecalis TN2OO5 by 50% was
      11 mg/L, and its MIC was 12.5 mg/L. Ceftazidime and cefmenoxime, which were
      inactive at 100 mg/L, showed no affinity for PBP 5 at this concentration.
      Ampicillin, benzylpenicillin and imipenem showed higher affinity for PBPs 3/4 and
      PBP 5 than cefozopran, and their MICs were lower than that of cefozopran. No
      correlation between MICs of the test compounds and the affinity for PBP 1, 2 or 6
      was found. These results suggest that cefozopran exhibits antimicrobial activity
      against E. faecalis TN2OO5 by binding to PBP 5.

PMID- 9182118
TI  - In-vitro activity of carbapenem antibiotics against beta-lactam susceptible and
      resistant strains of Burkholderia pseudomallei.
AB  - Four carbapenem antibiotics were tested for their in-vitro activities (MICs, MBCs
      and time-kill studies) against Burkholderia pseudomallei. The carbapenems were
      all more active than either ceftazidime or co-amoxiclav against strains of B.
      pseudomallei with a normal susceptibility pattern. Biapenem was the most active
      antibiotic tested. All four carbapenems retained bactericidal activity against 24
      strains of B. pseudomallei with reduced susceptibility to ceftazidime and/or co
      amoxiclav.

PMID- 9182119
TI  - Combination of 5-flucytosine and capsule-binding monoclonal antibody in the
      treatment of murine Cryptococcus neoformans infections and in vitro.
AB  - The efficacy of combination therapy with 5-flucytosine and an IgG1 monoclonal
      antibody to Cryptococcus neoformans capsular glucuronoxylomannan was studied in
      vitro with J774. 16 murine macrophage-like cells and in vivo in murine
      cryptococcal infection. The combination of 5-flucytosine and IgG1 was more
      effective in reducing the numbers of C. neoformans colony-forming units in vitro
      and in vivo than either agent alone.

PMID- 9182120
TI  - Impact of glycopeptide therapy after hospital discharge on inpatient costs: a
      comparison of teicoplanin and vancomycin.
AB  - Data were collected prospectively from 59 patients receiving vancomycin and 20
      patients receiving teicoplanin. The mean daily drug cost was 52.40 pounds for
      teicoplanin and 31.13 pounds for vancomycin; the 95% Confidence Intervals (CI)
      for the difference in mean drug costs varied between 14.40 pounds and 28.10
      pounds in favour of vancomycin. Use of a loading dose of teicoplanin
      significantly increased mean daily drug costs if the duration of treatment was
      less than 10 days. Costs of preparation, administration and monitoring were
      consistently higher for vancomycin than for teicoplanin and inclusion of these
      costs reduced the difference in mean daily costs to 13.01 pounds (95% CI 6.10 to
      19.90 pounds). In Dundee 11 of 20 patients who received teicoplanin had received
      some of their treatment after discharge from the hospital and a survey of UK
      hospitals confirmed that teicoplanin treatment after discharge is being used in a
      wide range of conditions. The median proportion of teicoplanin treatment in
      Dundee given after discharge was 28.4% for each patient who received the drug:
      the median proportion of non-inpatient therapy was 50% per patient of those who
      received any teicoplanin treatment after discharge. Assuming that teicoplanin
      costs 20 pounds per day more than vancomycin, use of teicoplanin implies an
      investment of 70.42 pounds to gain one hospital day through earlier discharge of
      patients receiving teicoplanin.

PMID- 9182121
TI  - Antiviral activity of local anaesthetic agents.

PMID- 9182122
TI  - Over-the-counter availability of antibiotics.

PMID- 9182123
TI  - Changes in beta-lactam antibiotic susceptibility and beta-lactamase production of
      clinical isolates of Bacteroides and Prevotella species over a 9 year period.

PMID- 9182124
TI  - Characterization of flavonoids in extracts from four species of Epimedium by
      micellar electrokinetic capillary chromatography with diode-array detection.
AB  - A micellar electrokinetic capillary chromatographic (MEKC) method with diode
      array detection is developed for the characterization of pharmacologically active
      flavonoids in extracts prepared from Epimedium brevicornum, E. humanense, E.
      coactum, and E. truncatum. The pK(a) values of icarin, epimedin B, and epimedin C
      are determined by spectrophotometry. Optimal separation of icarin, epimedin B and
      C, and eight other compounds is achieved by determining pK(a) values and by
      systematically optimizing electrolytic and instrumental parameters. The
      repeatability of analyses and the reliability of identification are evaluated by
      the marker technique. Calculated for relative migration times of flavonoids in
      the extracts, the repeatability of the analyses varies from 0.7 to 6.4% (nine
      replicates). For migration indices calculated with two markers, however, the
      repeatability almost falls below 0.5%. The distribution of the flavonoids is
      found to differ both qualitatively and quantitatively among the four species. The
      MEKC technique appears to provide a powerful tool for the identification and
      quality control of plant drugs and for phytotaxonomic investigations.

PMID- 9182125
TI  - Assuring college student health.

PMID- 9182126
TI  - Spinonin, a novel glycoside from Ononis spinosa subsp. leiosperma.
AB  - The roots of Ononis spinosa subsp. leiosperma (Leguminosae) afforded a new
      glycoside, spinonin (1), possessing a novel skeleton, in addition to the known
      isoflavonoid glycoside, ononin [7beta-(glucosyloxy)formononetin] (2) and the
      known pterocarpan, 7-demethoxy-7-D-(glucosyloxy)homopterocarpin (3). The
      structure of the new isolate was elucidated by spectral methods including 1H and
      13C NMR, COSY, APT, HETCOR, HMBC, NOESY, CD, FABMS, HRMS, EIMS, CIMS, and some
      chemical reactions. Spinonin was inactive against a number of human cancer cell
      lines and HIV-1 reverse transcriptase. The compounds 1 and 3 showed weak activity
      against Pseudomonas aeruginosa, whereas 2 was active against beta-hemolytic
      Streptococcus.

PMID- 9182127
TI  - Perhydrogenation of tabersonine, ans Aspidiosperma indole alkaloid.
AB  - The natural indole alkaloid (-)-tabersonine (1) easily provided (-)
      decahydrotabersonine (4a), isolated as dihydrochloride (4b), by catalytic
      hydrogenation. Saponification of 4a led to the beta-amino acid 5. A binding study
      of 1, 4b, and 5 on various receptors and ionic channels showed that none of the
      compounds had a strong affinity for the receptors tested.

PMID- 9182128
TI  - 10-Epi-olguine from Rabdosia ternifolia.
AB  - An unsaturated lactone, 10-epi-olguine (1), has been isolated from Rabdosia
      ternifolia (D. Don) Hara. The structure was established by spectroscopic and X
      ray crystallographic analyses. The compound displayed modest cytotoxicity in
      several human cancer cell lines.

PMID- 9182129
TI  - Proceedings of the International Symposium of the 50th Anniversary of Water
      Fluoridation. Grand Rapids, Michigan, September 1995.

PMID- 9182130
TI  - Proceedings of the 1st International Conference on Immunology and Aging.
      Bethesda, Maryland, June 16-19, 1996.

PMID- 9182131
TI  - [Coagulase-negative staphylococci isolated from cases of infective endocarditis].
AB  - In this study we investigated the properties of 47 strains of coagulase-negative
      staphylococci (CNS) isolated from patients with infective endocarditis (IE) and
      61 strains of CNS isolated from the skin flora of healthy people. Significant
      differences between the properties of CNS from IE and from the skin flora were
      seen in the production of protease, lipase, fibrinolysin, siderophore and the
      ability of hydrophobic CNS strains to adhere to buccal epithelial cells. CNS from
      IE and from the skin flora did not differ in the production of glycocalyx,
      capsule, hemolysin and fibronectin and collagen binding. Multiple resistant
      strains were present among CNS isolated from patients with IE.

PMID- 9182132
TI  - [Some factors influencing the number of staphylococci in the mouth and throat of
      children].
AB  - The relationship between the count of polymorphonuclear granulocytes in blood and
      also between the percentage of oral and pharyngeal streptococci showing
      antagonistic activity on the indicator strain Staphylococcus aureus 209P and the
      number of staphylococci in the oral cavity and pharynx were investigated. The
      study comprised 92 children, of both sexes, aged 4-15; among them there were 48
      children with the decreased number of circulating polymorphonuclear granulocytes
      due to the treatment of acute lymphoblastic leukaemia (ALL). A statistically
      significant negative correlation between the number of polymorphonuclear
      granulocytes in blood and the count of oral and pharyngeal staphylococci (both
      coagulase-negative and coagulase-positive) in children with ALL as well as in
      healthy children was revealed. The Pearsons linear correlation coefficients
      between these parameters were r = -0.364 (p < 0.001) and r = -0.313 (p = 0.019)
      for the oral cavity and for the pharynx, respectively. The streptococci showing
      antagonistic activity had only some influence on the count of staphylococci in
      the oral cavity. The Pearson's linear correlation coefficient between this number
      and the count of staphylococci in 1 ml of saliva was r = -0.382 (p < 0.001).

PMID- 9182133
TI  - [Antagonistic properties of bacterial flora in the mouth and throat of children].
AB  - The research concerned the antagonistic activity of oral and pharyngeal bacterial
      flora in 44 children, of both sexes, aged 4-15. These properties were estimated
      basing upon in vitro inhibition of the growth of the standard indicator strains
      Staphylococcus aureus 209P and Escherichia coli K-12. Bacteria, both aerobic as
      well as anaerobic, inhibiting the growth of S. aureus 209P were found in every
      sample. The median percentages of bacteria showing these properties were not
      significantly different in both environments and they ranged from 25% to 33%. The
      antagonistic activity of oral and pharyngeal bacterial flora against the
      indicator strain E. coli K-12 was significantly lower when compared with the
      activity against the staphylococcal strain.

PMID- 9182134
TI  - [Staphylococcal utilization of siderophores produced by bacilli of the genus
      Bacillus].
AB  - The ability of utilization by 24 staphylococcal strains of the siderophores of B.
      megaterium PCM 2010 and B. subtilis S was investigated. B. megaterium PCM 2010
      produced hydroxamate class siderophores and B. subtilis S-catecholate class. The
      majority of staphylococcal strains--thirteen--could utilize these siderophores:
      eight strains from both these species and three strains did not possess any
      receptors for these chelators. The staphylococcal strains producing catecholate
      siderophores utilized catecholate chelators from B. subtilis S.

PMID- 9182135
TI  - [Evaluation of external laboratory test results for the correct identification
      and determination of chemotherapeutic sensitivity of staphylococci in
      bacteriologic provincial laboratories of sanitary-epidemiologic stations in
      1995].
AB  - In the tests bacteriological laboratories participated in 45 sanitary
      epidemiological stations. Each station was given two strains of staphylococci: S.
      epidermidis and S. aureus homogeneously resistant to methicillin (MRSA) or S.
      aureus sensitive to methicillin (MSSA), and S. aureus coagulase-negative and
      clumping-factor-positive strain. The analysis was carried out of the results of
      control identifications of strains of the determinations of the sensitivity of
      the identified strains to antibiotics. Among the studied strains the greatest
      difficulty in identification were caused by the coagulase-negative strain of S.
      aureus. In the determination of the sensitivity of the control strains to
      chemotherapeutic agents abnormalities were found in the technique of antibiogram
      performing and incorrect selection of discs for antibiograms as well as erroneous
      interpretation of the results.

PMID- 9182136
TI  - [Occurrence of virulent plasmids in strains of Yersinia obtained from various
      sources].
AB  - By the method of alkaline lysis the occurrence was studied of plasmid DNA in 122
      strains of Yersinia. In 29 strains a single plasmid was found with characteristic
      growth of the organism on CRMOX (CRMOX+) medium. These features are encoded by
      genes located on the pYV virulence plasmid. The group of Yersinia strains
      possessing the virulence plasmid included 27 strains of Y. enterocolitica 0:3
      isolated from clinical materials, among them 21 strains isolated from patients
      between January and September 1996, while the remaining two strains with the
      virulence plasmid belonged to Y. pseudotuberculosis antigenic group I. Following
      restriction analysis with the EcoRI enzyme of the virulence plasmids isolated
      from 27 strains of Y. enterocolitica 0:3 occurrence of only one restriction
      endonuclease pattern agreeing with the virulence plasmid pattern of Y.
      enterocolitica 0:3 strains reported in the literature was found in all strains.
      On the other hand, the restriction analysis of the virulence plasmids obtained
      from Y. enterocolitica 0:3 and Y. pseudotuberculosis I strains showed evident
      differences between these plasmids in the size of the particle and the
      restriction pattern. The plasmid size calculated on the basis of the analysis of
      the restriction endonuclease patterns for virulence plasmids isolated from the
      strains of Y. enterocolitica 0:3 and Y. pseudotuberculosis I was 71.5 thousands
      and 62.7 thousands of base pairs respectively, and was in the range 60-75
      thousands bp (40-50 Mda) reported in the literature for virulence plasmids of
      Yersinia. The study showed that finding of characteristic growth of Yersinia
      organisms on the CRMOX medium can be useful for the detection of strains
      containing the pYV virulence plasmid and for the determination of their potential
      pathogenicity.

PMID- 9182137
TI  - [Evaluation of results for controlling the variability of diagnostic tests for
      intestinal bacteria introduced to the laboratories of sanitary-epidemiologic
      stations in 1995].
AB  - In this testing bacteriological laboratories of 49 epidemiological stations were
      participating. Eleven control tests were prepared in form of lyophilize faecal
      samples containing three different organisms in each sample with pathogenic
      organisms present in each of 10 tests (a different species in each test) along
      with a non-pathogenic Enterobacteriaceae strain, while the 11th test contained
      only organisms belonging to physiological intestinal flora. Each laboratory
      received two different tests for doing them. The following bacterial strains were
      used S. oranienburg var, lac+ S. muenster, S. infantis, S. sonnei, S. flexneri,
      A. hydrophila, Y. enterocolitica, E. coli 018, E. coli 026, E. coli 0124, and as
      accompanying organisms: C. freundii var lac+ and lac-, P. mirabilis and H. alvei.
      Among 49 participating laboratories 31 (63.3%) detected the etiological
      infectious agent in both samples, or its absence was shown in the 11th test. In
      23 laboratories (46.9%) the cultured organisms were species-grouped or their
      serological type was established, in the remaining 8 laboratories (16.3%) the
      identification was incomplete or serological type was not correctly recognized.
      In 15 laboratories (30.6%) the infectious agent was found in only one test, and
      in 12 of these laboratories (25.5%) the cultured organism were identified
      correctly completely, and in 3 (6.1%) identification was incomplete or
      serological type was not correctly recognized. In 3 (6.1%) among 49 laboratories
      the infectious agent was not found in any test. The study made possible an
      insight into the reliability of the diagnostic tests for Enterobacteriaceae
      carried out in the sanitary-epidemiological stations. The use of faeces
      simulating samples made possible to assess not only the correct identification of
      the isolated organisms, but also to trace the course of the diagnostic management
      used in each laboratory for testing of faeces samples.

PMID- 9182138
TI  - [Microbiological evaluation of ciprofloxacin efficacy for treatment of urinary
      tract infections].
AB  - An attempt has been undertaken to evaluate the aetiology of urinary tract
      infections in a large group of patients and to determine the resistance to
      ciprofloxacin during therapy, and the efficacy of the drug in treating of urinary
      tract infections. 52 patients with urinary tract infections were treated with
      ciprofloxacin. Ciprobay by BAYER was used in coated 500 mg tablets twice a day
      and intravenous solutions in 200 mg dosages every 12 hours for 10-14 days
      depending on the clinical condition. Microbiological tests were made according to
      general methods. Sensitivity evaluation to ciprofloxacin was done using E-tests
      by AB Biodisk and dilution tests. The most common a etiology of urinary tract
      infections were Gram-negative Enterobacteriaceae rods, mainly E. coli.
      Ciprofloxacin gave the best results against Enterobacteriaceae rods (100%
      eradications). In other infections, effective therapy was possible after
      determining of the sensitivity in vitro. S. haemolyticus bacteria tended
      significantly towards resistance to ciprofloxacin during therapy.

PMID- 9182139
TI  - [Occurrence of rota-I adenoviruses in diarrhea states of children].
AB  - 98 children aged 6 weeks to 5 years with diarrhoea were examined. Rotaviruses and
      adenoviruses were detected by latex tests Rotalex and Adenolex produced by Orion
      Diagnostica. Rotaviruses were found in 20.4% of cases, most frequently in
      children of the age from 6 to 18 months. Adenoviruses were found in 11.2% of
      cases, most frequently in children of the age from 18 months to 5 years, mainly
      in mixed infection by- and adenoviruses. Viruses infection were most rare in
      infants aged from 6 weeks to 6 months. In 4.1% studied cases the coexisting of
      viral and bacterial infection was observed (K. pneumoniae, E. coli).

PMID- 9182140
TI  - [Frequency of HPV infection and the level of ascorbic acid in serum of women with
      cervix dysplasia].
AB  - The effect of HPV infection on cervix dysplasia development and ascorbic acid
      level in 528 women was studied. HPV-DNA was estimated using Digene Hybride
      Capture System and ascorbic acid by color metric method with 2,4
      dinitrophenylhydrazine at 520 nm. HPV infection can be connected with the risk of
      cervical pathology and cervical cancer. Besides, we observed lower level of
      ascorbic acid in groups of women with CIN, Ca in situ and HPV infected.

PMID- 9182141
TI  - [Use of polymerase chain reaction (PCR) for diagnosis of toxoplasmosis].
AB  - The aim of the study was to assess the value of PCR method in laboratory
      diagnosis of T. gondii infections. The study was based on the identification of a
      fragment of B1 gene of Toxoplasma gondii 461 base pairs in length in 124 samples
      of blood, CSF, amniotic fluid and aqueous fluid obtained form humans and
      experimentally infected animals. Positive PCR results were found with CSF samples
      and blood sample from men. Moreover, the results were positive with blood samples
      from mice and rabbits bled on 5, 6, 11 and 12 days after infection. The obtained
      results showed that PCR is very useful in the laboratory diagnosis of
      toxoplasmosis, especially in cases suspected of cerebral toxoplasmosis.
      Furthermore, the results demonstrated that neurotoxoplasmosis occurs in Poland,
      more frequently that it is realized at present, however, the cases are not
      recognized because toxoplasmosis is not taken into account in differential
      diagnosis. Because of short and irregular parasitaemia, PCR is of limited value
      in the diagnosis of blood samples.

PMID- 9182142
TI  - [Detection of specific toxoplasma class A antibodies: a comparison of diagnostic
      usefulness of commercially available diagnostic kits].
AB  - Diagnostic significance of the presence of specific anti-Toxoplasma gondii IgA
      antibodies was discussed with particular reference to the cases of congenital
      toxoplasmosis and infections in pregnant women. Furthermore, the possibilities of
      testing for anti-Toxoplasma IgA antibodies with commercially available diagnostic
      kits were presented. From amongst the examined 5 diagnostic kits, Platelia Toxo
      IgA and ISAGA Plus IgA/IgM showed the highest sensitivity and specificity.

PMID- 9182143
TI  - [Synergistic action of penicillin and immunoglobulin for intravenous (IVIG) use].
AB  - Combined effects of intravenous immunoglobulin and antibiotic in killing bacteria
      are of interest with extending clinical use of IGIV. Since the agents differ in
      antibacterial activity exerted by each of them, and their influence on the other,
      it is difficult to evaluate the combined effect in vitro. In our experiments the
      titer of antibody, and the killing of B Streptococcus type 090R, phagocytosis by
      chemiluminescence were examined in opsonic mixture. This mixture consist of IVIG,
      fresh serum, and neutrophils plus penicillin or without. The effect of combined
      IVIG and penicillin was higher than the effects of separate activities on
      bacteria. This observations suggest that the combination of IVIG and penicillin
      potentially useful in the treatment of GBS infection in some cases.

PMID- 9182144
TI  - [Evaluation of the usefulness of the peripheral test for determination of rabies
      vaccine potency].
AB  - The results of CDC peripheral test for potency of rabies vaccines were compared
      to the results obtained in the NIH intracerebral test recommended by the WHO. We
      did not find statistically significant differences in the potency of tested
      rabies vaccines by CDC and NIH tests.

PMID- 9182145
TI  - [LAL test used for detection of undesirable biologically active substances in
      biopreparations].
AB  - Detection of bacterial endotoxin was performed in four groups of biopreparations:
      IVIG, virus and bacterial vaccines and antibiotics. The 44 samples of
      biopreparations were tested by the qualitative LAL-test (gel-clot) and some of
      them (22 samples) by the quantitative, LAL-test (chromogenic end-point). The
      concentration of endotoxin in 10 samples of IVIG was in the range from 0.457
      EU/ml to 19.46 EU/ml. Only 4 of them did not exceed the limit recommended by FDA
      for human globulins (5 EU/ml). In the 9 samples out of 10 samples of virus
      vaccines the presence of endotoxin was in the range from 0.06 to 0.15 EU/ml. The
      concentration of endotoxin in 10 samples of bacterial vaccines determined by gel-
      clot method was below sensitivity of test (2 EU/ml). In antibiotics we did not
      find the presence of endotoxin in the range recommended by Ph. Eur. 1995 limits
      (0.1-0.2 EU/ml). The presented data show the necessity for requirements
      elaboration for each type of biopreparations.

PMID- 9182146
TI  - [Pathological gambling].

PMID- 9182147
TI  - [Professor Conny Nordin: pathological gambling--a challenging phenomenon!].

PMID- 9182148
TI  - [How does Bosse Ringholm calculate? The county council saves billions with the
      new tariffs].

PMID- 9182149
TI  - [For better and cheaper health care. Health care based on primary health care
      services is good for Sweden].

PMID- 9182151
TI  - [The difference between SEM and SD].

PMID- 9182150
TI  - [Persons with vision disorders must be dexterous].

PMID- 9182152
TI  - [How to guarantee the quality of drug prescriptions].

PMID- 9182153
TI  - [The National Board of Health and Welfare is assisted by medical societies when
      planning educational courses].

PMID- 9182154
TI  - [The right of licensed physicians to prescribe drugs].

PMID- 9182155
TI  - [The Department of Justice is insufficiently informed about the mental health of
      prisoners].

PMID- 9182156
TI  - [Mosquito net against malaria is recommended].

PMID- 9182157
TI  - [Why are the interns declared incompetent by the National Board of Health and
      Welfare?].

PMID- 9182158
TI  - [Measurement of HIV-RNA in blood is of great predictive value].

PMID- 9182159
TI  - [A scientist's day-dream or future reality? Specific immunotherapy against
      cancer].

PMID- 9182160
TI  - [Picture of poisoning in citalopram overdose. Convulsions and ECG symptoms can
      occur].

PMID- 9182161
TI  - [The Balint groups for future physicians. A way of contribution to professional
      maturity].

PMID- 9182162
TI  - [Hydatidiform mole may cause symptoms in many organs].

PMID- 9182163
TI  - [Watch out for the false low levels of hCG!].

PMID- 9182164
TI  - [New techniques for retinal surgery. Cell transplantation, a future therapeutic
      method?].

PMID- 9182165
TI  - [Laser in eye surgery. New techniques refine diagnosis and therapy].

PMID- 9182166
TI  - [Research on emotions is advancing. Psychotherapists are leaving the trenches].

PMID- 9182167
TI  - [Swedish psychiatrists are teaching in the Baltic countries. A developmental
      project in cooperation with friendship-clinics].

PMID- 9182168
TI  - [An interview study of close relatives of pathological gamblers: the worst is to
      feel deceived and cheated].

PMID- 9182169
TI  - [Substance abuse testing at the workplace. When is it justified?].

PMID- 9182170
TI  - [Ethics and drugs. Black Jack is creeping to physicians' prescription pads].

PMID- 9182171
TI  - [Prima--25 years of waiting for general practitioners!].

PMID- 9182172
TI  - [A uniform description of endovascular surgery].

PMID- 9182173
TI  - [A follow-up of resources used in medical education is required].

PMID- 9182174
TI  - [Medical education needs restructuring].

PMID- 9182175
TI  - [Same conditions for both private and public health care services].

PMID- 9182176
TI  - [Great progress in geriatric medicine. But still balancing between over-and under
      diagnosing].

PMID- 9182177
TI  - [Diagnosis is urgent when malaria is suspected!].

PMID- 9182178
TI  - [Effects, possibilities and limits. Cytostatic therapy of small cell and non
      small cell lung cancer].

PMID- 9182179
TI  - [Severe falciparum malaria among travellers to Thailand. Blood exchange and
      artemisinine treatment are therapeutic alternatives].

PMID- 9182181
TI  - [Complex memory function for mental trauma. Memory and forgetting ae necessary
      for the emotional adaptation process].

PMID- 9182180
TI  - [Carcinoembryonic antigen, CEA, in colorectal cancer. An insensitive marker which
      may be excluded from follow-ups].

PMID- 9182182
TI  - [Hospital infections make health services more expensive. Hygienic measures in
      hospitals are economically beneficial].

PMID- 9182183
TI  - [A national document on clinical nutrition. Developmental work for improvement of
      medical education].

PMID- 9182184
TI  - Evaluating lung volume reduction surgery.

PMID- 9182185
TI  - [A comparative study of the somatic, excretory-secretory and egg antigens of
      Opisthorchis felineus].
AB  - Electrophoretic analysis showed that the somatic, excretory and secretory, and
      egg antigens of O. felineus have a complex protein composition. They were found
      to have 20, 11, and 25 proteins, respectively. On titration of the antigens, by
      using a constant dose of immune sera, the excretory and secretory antigen was
      detected in concentrations 50-100 less than the somatic and egg antigens. Rabbit
      immune sera effectively interacted with the proteins 116, 105, 80, 70, 60, 50,
      44, 40 kD as part of the excretory and secretory antigen, with the proteins 105,
      80, 70, 60, 50, 44, 40 and 32 kD as part of the somatic antigen, with the
      proteins p70, p60, p50, p28, p25 and p24 kD as part of the egg one. The limited
      human immune responses revealed by the author on O. felineus invasion, which was
      associated with the excretory and secretory and somatic p105 and three egg
      antigen proteins, such as p74, p70, p64 clearly indicate further ways of
      improving the immune diagnosis of opisthorchiasis.

PMID- 9182186
TI  - [The use of immunoblotting for studying Opisthorchis felineus (Rivolta, 1884)
      antigens].
AB  - Opisthorchis somatic, metabolic, and tegumental antigens were studied by using
      immunoblotting. It was shown that among several antigenic components, only the
      somatic protein with a molecular weight of about 100 kD failed to react with
      noninvased human sera.

PMID- 9182187
TI  - [The susceptibility of different animal species to synanthropic and natural
      populations of Trichinella].
AB  - Pigs have been found to be highly susceptible to the synanthropic (domestic)
      population of Trichinella [correction of Trachina] and weakly susceptible to the
      natural (native) one. Fur-bearing animals (polar foxes and foxes) are more
      susceptible to the natural population of Trichinella [correction of Trachina],
      but minks are equally sensible to the two variants of T. spiralis. In the host's
      body, synanthropic Trichinella [correction of Trachinas] form capsules of lemon
      like, less frequently, oval shape, but the native population do round capsules.
      There is larval adaptation when Trichinella [correction of Trachina] larvae enter
      the nonspecific host's body after their prepassage through the organism of
      domestic carnivorous animals (cats, dogs). The pig is successfully infected with
      T. spiralis nativa via the cat or dog; the infection rate is approximately close
      to that observed during control infection of pigs with synanthropic Trichinella
      [correction of Trachina].

PMID- 9182188
TI  - [The comparative morphology of Trichinella spiralis and Trichinella
      pseudospiralis].
AB  - The comparative study of the morphology of invasive larvae and mature males and
      females T. spiralis and T. pseudospiralis at the head end of the parasites has
      revealed 14 papillae which are located in 3 circles and 2 which are placed
      bilaterally, 2 amphidae, and a lanceolar stiletto with a spicular cutting edge.
      There are no differences in the structure of the heads of these two Trichinella
      species. The larval cuticle is decorated only with cross folds while longitudinal
      small-sized folds which are arranged in regular rows appeared in mature species.
      The vulva in females is located at the levels of a fifth of the body from the
      head, it is slit-like and oval, that in T. pseudospiralis is situated at the
      cuticular projection. The anus in T. pseudospiralis larvae is as a cross oval
      slit, that in adult females is as a hemisphere, and in adult males it is
      coincident with the copulation pore. As for the structure of the pseudobursa,
      differences are found in the size and shape of copulation processes, in the
      arrangement of pre- and postanal papillae against the cloaca, in the size of the
      formed cuticular projections in T. spiralis, in the shape of the cloacal hole. In
      the unscrewed copulatory bell, it opens transversely in T. spiralis and
      vertically in T. pseudospiralis.

PMID- 9182189
TI  - [An analysis of malaria morbidity in the Republic of Tajikistan].

PMID- 9182190
TI  - [The technology for manufacturing antiparasitic preparations. 8. The preparation
      rilanid and its use for treating fascioliasis and intestinal nematodiases].
AB  - A procedure has been developed to prepare the anthelminthic Rilanide as a fine
      dispersed formulation. The therapeutical dose of the agent in fascioliasis and
      intestinal nematodiasis is 60 mg/kg (for sheep), if given alone, and 100 mg/kg,
      if added to feed.

PMID- 9182191
TI  - [New approaches to the eradication of enterobiasis in children].
AB  - The paper outlines the results of studies dealt with the detection of risk
      factors and groups for enterobiasis, the efficiency of the treatment of children
      suffering from the disease with medamine, biologicals, and Normase. It is shown
      that risk factors may include an abnormal course of antenatality, minor
      developmental malformations (diastema, dystrophy, abnormalities of the eye, hand,
      foot, etc.), as well as early artificial feeding of babies (before they reach 3
      months of life). Enterobiasis is found to have a negative influence on the
      physical, nervous, and mental development and suppression of non-specific
      immunity in children, which is suggested by the reduction in salivary lysozyme
      activity, which is lower than the normal level and on blood alpha-interferon
      production. There is strong evidence for the considerable immunosuppressive
      effects of enterobiasis on the formation of a postvaccinal immunity against
      measles. When given in a single course dose, medamine shows a 100% efficiency in
      the treatment of enterobiasis. Moreover, bificol, bifidumbacterin, and Normase
      may be useful to enhance the treatment efficiency and children's recovery from
      enterobiasis.

PMID- 9182192
TI  - [An immunoenzyme test system for the identification of typical and atypical
      strains of the plague microbe].
AB  - The authors have developed the optimal variant of the enzyme immunoassay system
      that contains plague murine monoclonal and equine polyclonal immunoglobulins and
      identified all plague microbe strains at a high sensitivity (3.84 m.cl/ml). The
      cross reactivity of monoclonal antibodies with some pseudotuberculosis agent
      strains does not prevent from using the developed test system for laboratory
      diagnosis of plague, particularly while isolating atypical (capsule- or plasmid
      free) variants of Y. pestis, taking into account parallel special diagnostic
      tests for pseudotuberculosis.

PMID- 9182193
TI  - [Asymmetry of the chaetae in fleas (Citellophilus tesquorum) as a possible marker
      of their capacity for blocking].
AB  - The fluctuating asymmetry was studied according to two bilateral numeric features
      of chaetaxy in groups of female Citellophilus tesquorum fleas. One group included
      insects with the recorded gizzard block during infection with the virulent plague
      agent strain. The fleas with the block were characterized by considerably higher
      levels of fluctuating asymmetry as compared with those without fleas.

PMID- 9182194
TI  - [Experience in using regression analysis for assessing the quality of the
      diagnosis of hemorrhagic fever with renal syndrome].
AB  - A new approach has been developed to evaluate the adequacy of HFRS clinical
      diagnosis, by using regression analysis of large selections. The HFRS morbidity
      rate and the antibody prevalence rate in man were viewed as a function and an
      argument of the function, respectively. An empiric model for one of the active
      HFRS endemic area (Saratov Province), characterizing the correlation between the
      immunity and morbidity rates has been elaborated. It calculates the theoretical
      morbidity level that corresponds to determine an immune portion of the population
      in each administrative area. The theoretical (counted) values were compared to
      the annually registered morbidity rates; their similarity has been estimated.
      Estimation of the adequacy of HFRS diagnosis in the examined region could have
      been admitted as satisfactory. However, various faults in the clinical
      identification of HFRS cases were found to occur in 14 of 44 districts of this
      region. Hyperdiagnosis was made in the most active HFRS natural foci (broad
      leaved forests), but in the endemic areas being characterizes by moderate or low
      activity (forest-steppe and steppe districts). The results of the authors'
      calculations were shown to be generally in agreement with the data from the
      Regional Epidemiological Service reports which confirmed the adequacy of the
      proposed material.

PMID- 9182195
TI  - [The reaction of taiga ticks to an attractant. II. The rates of removing ticks
      from a population].
AB  - Catching ticks on the attractant-moistened napkins and on the flag (control)
      under field conditions during 5 days has demonstrated that a population of taiga
      ticks on the treated areas can be killed within 1-2 weeks when attractive
      acaricidal granules are applied.

PMID- 9182196
TI  - [Comparative data on the tick-borne encephalitis virus infectiousness of hungry
      and satiated taiga ticks (based on the results of an immunoenzyme analysis)].
AB  - The results of individual investigation of 25,500 Ixodes persulcatus ticks from
      east Siberia are presented. The ticks were collected from grass, men, and animals
      before their sticking and after feeding at different intervals. The quantity of
      positive specimens was 6-11 times higher among the fed ticks hungry ones and
      averaged 10.36 and 1.85%, respectively, at the first stage due to the higher
      aggression of the infected females at the first stage and due to viral
      replication when the tick had feed and its better recognition as the titers
      increased. The proportion of ticks having high levels of tick-borne encephalitis
      virus antigen among the fed ticks was also considerably higher. The content of
      virus antigen increased in proportion with the duration of feeding. There is a
      moderate correlation (r = 0.59) of the infection index of hungry and fed ticks in
      different years and in various areas. The findings suggest that the fed ticks
      should be used as an additional marker for the features of tick-borne
      encephalitis virus circulation.

PMID- 9182197
TI  - [Spontaneous tick infection with Borrelia and the degree of their individual
      infectiousness in different landscape subzones of Tyumen Province].

PMID- 9182198
TI  - [A circulation study of California serogroup and Batai viruses (fam.
      Bunyaviridae, genus Bunyavirus) on the territory of Saratov Province].
AB  - Examining 337 sera from Saratov healthy residents in the neutralization test with
      Tyaginya and Inco viruses has revealed 56 positive results (16.6%), of which 19
      (5.6%) reacted only with Tyaginya virus, 13 (3.9%) did only with Inco virus, and
      24 (7.1%) simultaneously with these two viruses. Batai virus antibodies were not
      detected in the population. Among 80 bovine serum samples collected in the
      Saratov district of the region, type-specific antibodies to Tyaginya virus were
      found in 10 (12.5%) and a serum (1.2%) reacted with Tyaginya and Inco viruses; 49
      sera (61.2%) contained Batai virus antibodies.

PMID- 9182199
TI  - [A method for testing new film-forming larvicides as regulators of the population
      count of blood-sucking mosquitoes].
AB  - To enhance requirements for environmental protection and the emergence of
      mosquito populations resistant to insecticides demands that new methods and means
      of controlling the insects should be developed. To test surfactants having
      insecticidal effects was a trend of these studies. No mention of the above group
      of insecticides in the well-known "Methods for Testing New Chemicals for the
      Control of Blood-Sucking Diptera" (1970) made it necessary to work out "Methods
      of Testing New Film-Forming Larvicides as Regulators of the Population of Blood
      Sucking Mosquitos" which may be used by the workers of the centers of state
      sanitary and epidemiological surveillance and research institutes.

PMID- 9182200
TI  - [Test results on the insecticidal activity of Oradelt and Omait against rodent
      fleas].
AB  - The paper presents the results of trials of the commercial agents oraldelt and
      omaita as an insecticide against rodent fleas. The agents were found to produce
      highly toxic effects on fleas. The field trials established the high poolecidal
      effectivity of oraldelt in the mountain suslik habitats. The commercial agent
      oraldelt containing 0.05% of decamethrin may be recommended for the control of
      fleas in the foci of suslik-type plague.

PMID- 9182201
TI  - [Structural changes in the genital system of nematodes of the suborder
      Strongylata after exposure to anthelmintics].

PMID- 9182202
TI  - [New cases of human dirofilariasis].

PMID- 9182203
TI  - [The disinfection of fish in the family Cyprinidae of Opisthorchis felineus Riv.
      metacercariae by the combined use of acetic acid and table salt].
AB  - The studies were aimed at optimizing the procedure for disinfection of carps from
      the larvae of a pathogen of opisthorchiasis. The effects of different
      concentrations of acetic acid solutions on the viability of encysted O. felineus
      metacercariae isolated from ide (Leuciscus idus L.) tissue, as well as on that of
      larvae located in the fish muscles were examined by consequently using the
      solutions of acetic acid and salt. Acetic acid solutions (3 and 6%) are minimally
      effective in suppressing the viability of encysted O. felineus metacercariae
      isolated from fish tissues, 6% acetic solution being approximately 6 times
      higher. Acetic acid pretreatment of fish led to the higher salt penetration rate
      into the muscles of fish when it was salted thereafter and accelerated the death
      of O. felineus metacercariae. To correct the way of salting the fish invaded by
      Opisthorchis metacercariae, 4-hour fish presoaking in 6% acetic acid solution is
      most promising, which promotes the acceleration of the death of metacercariae and
      exerts no noticeable effect on the marketable state and taste of fish.

PMID- 9182204
TI  - Cigar smoking among teenagers--United States, Massachusetts, and New York, 1996.
AB  - Cigar smoking can cause cancers of the oral cavity, larynx, esophagus, and lung
      and chronic obstructive pulmonary disease. In addition, cigars contain
      substantial levels of nicotine, an addictive drug. Despite these health risks,
      total cigar consumption in the United States was approximately 4.5 billion cigars
      in 1996, and consumption of larger cigars increased by 44.5% from 1993 through
      1996 (from 2,138 million cigars to 3,090 million cigars, respectively. This
      report presents estimates of the prevalence of cigar smoking among youth based on
      analyses of data from the Robert Wood Johnson Foundation's (RWJF) 1996 National
      Study of Tobacco Price Sensitivity, Behavior, and Attitudes Among Teenagers and
      Young Adults; a 1996 survey by the Massachusetts Department of Public Health
      (MDPH) of high school and junior high school students; and the Roswell Park
      Cancer Institute's 1996 Survey of Alcohol, Tobacco, and Drug Use in two New York
      counties. The analyses indicate that, during the year before being surveyed,
      26.7% of U.S. and 28.1% of Massachusetts high school students reported having
      smoked at least one cigar and that 13%-15% of ninth grade students in two New
      York counties reported having smoked cigars during the previous 30 days.

PMID- 9182205
TI  - Illegal sales of cigarettes to minors--Mexico City, Mexico, 1997.
AB  - Because of the increasing prevalence of tobacco use among youth in the United
      States and Mexico, in 1996 the United States-Mexico Binational Commission (US
      MBC) Health Working Group identified prevention of tobacco use, with an emphasis
      on adolescents, as one of its four priority health concerns. From 1970 to 1990,
      annual death rates for the leading causes of smoking-related deaths in Mexico
      nearly tripled and, in 1992, an estimated 10,253 persons in Mexico died as a
      result of smoking-related diseases, 9% of all deaths that year. In addition, from
      1988 to 1993, the prevalence of current smoking among minors aged 12-17 years
      increased from 6.6% to 9.6%, respectively (in Mexico City, the 1993 prevalence
      was 12.8%), and in 1993, 72% of adult smokers in Mexico reported becoming regular
      smokers before age 18 years. Although since 1984 the General Health Law of Mexico
      has prohibited the sale of tobacco products to minors aged < 18 years, compliance
      with this law has not been assessed. As part of the Mexican national program to
      reduce the prevalence of cigarette smoking among children and adolescents and in
      support of the goals of the US-MBC, during 1997 the General Directorate of
      Epidemiology (GDE) in the Secretariat of Health (SOH) conducted a survey of
      tobacco outlets in Mexico City to assess the percentage of retailers willing to
      sell cigarettes to minors. This report summarizes the results of the survey,
      which indicate that virtually no surveyed retailers asked minors attempting to
      purchase cigarettes about their age and that most retailers sold cigarettes to
      minors.

PMID- 9182206
TI  - Smoking-attributable mortality and years of potential life lost--United States,
      1984.
AB  - Cigarette smoking has been identified as the chief avoidable cause of death in
      the United States. Several estimates of mortality attributable to cigarette
      smoking have been reported, including 270,000 deaths for 1980 and 314,000 deaths
      for 1982. Published estimates vary considerably because of changing mortality
      rates, decreasing smoking rates, and differences in methods used. Smoking
      attributable mortality and years of potential life lost (YPLL) for 1984 are
      analyzed in this report.

PMID- 9182207
TI  - Outbreaks of cyclosporiasis--United States, 1997.
AB  - In April and May 1997, CDC received reports of seven event-associated clusters of
      cases of cyclosporiasis from five states (California, Florida, Nevada, New York,
      and Texas). Approximately 80 cases of infection with human-associated Cyclospora,
      a recently characterized coccidian parasite have been laboratory-confirmed. State
      and local health departments, CDC, and the Food and Drug Administration are
      conducting investigations to identify the vehicles of infection.

PMID- 9182208
TI  - Update: outbreaks of cyclosporiasis--United States, 1997.
AB  - During April and May 1997, CDC received reports of clusters of cases of
      cyclosporiasis in the United States. This report describes the preliminary
      findings of an investigation of an outbreak in New York and summarizes the
      findings from on-going investigations in other states.

PMID- 9182209
TI  - Dog-bite-related fatalities--United States, 1995-1996.
AB  - From 1979 through 1994, attacks by dogs resulted in 279 deaths of humans in the
      United States. Such attacks have prompted widespread review of existing local and
      state dangerous-dog laws, including proposals for adoption of breed-specific
      restrictions to prevent such episodes. To further characterize this problem and
      the involvement of specific breeds, CDC analyzed data from the Humane Society of
      the United States (HSUS) and media accounts in the NEXIS database. This report
      presents three recent cases of dog-bite-related fatalities (DBRFs), summarizes
      characteristics of such deaths during 1995-1996, and provides breed-specific data
      for DBRFs during 1979-1996. The findings in this report indicate that most DBRFs
      occurred among children and suggest approaches for prevention.

PMID- 9182210
TI  - Update: progress toward poliomyelitis eradication--South East Asia Region, 1995
      1997.
AB  - In 1988, the World Health Assembly established the goal of global poliomyelitis
      eradication by the year 2000. Since then, substantial progress has been reported
      from all World Health Organization (WHO) regions by implementing strategies to
      prevent, detect, and interrupt transmission of poliovirus. In WHO's South-East
      Asia Region (SEAR), the successful application of these strategies has resulted
      in a 96% decrease in the number of annually reported polio cases during 1989-1996
      (from 25,711 cases to 1116 cases). Acceleration of intensified surveillance
      continues to be critically important for identifying the remaining reservoirs of
      poliovirus circulation for targeted mass vaccination campaigns. This report
      summarizes data on progress in SEAR toward polio eradication as of April 1, 1997,
      and updates previous reports.

PMID- 9182211
TI  - Decreasing incidence of perinatal Group B streptococcal disease--United States,
      1993-1995.
AB  - Group B streptococcal (GBS) infections are the leading cause of bacterial disease
      and death among newborns in the United States and an important cause of morbidity
      among peripartum women and nonpregnant adults with chronic medical conditions.
      Disease in infants usually presents as sepsis, pneumonia or meningitis but also
      may include cellulitis or osteomyelitis. In 1990, GBS infections caused an
      estimated 7600 serious illnesses and 310 deaths among U.S. infants aged < or = 90
      days; infections among infants aged < 7 days (i.e., early-onset disease)
      accounted for approximately 80% of these illnesses. To determine the incidence of
      GBS disease during 1993-1995, CDC conducted surveillance for this disease in an
      aggregate population of 12.5 million persons with 190,000 annual live-born
      infants. This report summarizes the findings of surveillance in this population,
      which indicate that a statistically significant decline in the incidence of early
      onset GBS disease occurred in some surveillance areas.

PMID- 9182212
TI  - Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during
      percutaneous coronary revascularization.
AB  - BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with
      abciximab (a monoclonal-antibody Fab fragment directed against the receptor) has
      been shown to diminish ischemic complications among patients undergoing high-risk
      coronary angioplasty or directional atherectomy but increases bleeding
      complications. The widespread applicability of this treatment is unknown,
      particularly in view of the observed risk of hemorrhage. METHODS: In a
      prospective, double-blind trial, we randomly assigned patients undergoing urgent
      or elective percutaneous coronary revascularization at 69 centers to receive
      abciximab with standard-dose, weight-adjusted heparin (initial bolus of 100 U per
      kilogram of body weight); abciximab with low-dose, weight-adjusted heparin
      (initial bolus of 70 U per kilogram); or placebo with standard-dose, weight
      adjusted heparin. The primary efficacy end point was death from any cause,
      myocardial infarction, or urgent revascularization within 30 days of
      randomization. RESULTS: The trial was terminated at the first interim analysis,
      with 2792 of the planned 4800 patients enrolled. At 30 days, the composite event
      rate was 11.7 percent in the group assigned to placebo with standard-dose
      heparin; 5.2 percent in the group assigned to abciximab with low-dose heparin
      (hazard ratio, 0.43; 95 percent confidence interval, 0.30 to 0.60; P<0.001); and
      5.4 percent in the group assigned to abciximab with standard-dose heparin (hazard
      ratio, 0.45; 95 percent confidence interval, 0.32 to 0.63; P<0.001). There were
      no significant differences among the groups in the risk of major bleeding,
      although minor bleeding was more frequent among patients receiving abciximab with
      standard-dose heparin. CONCLUSIONS: Inhibition of the platelet glycoprotein
      IIb/IIIa receptor with abciximab, together with low-dose, weight-adjusted
      heparin, markedly reduces the risk of acute ischemic complications in patients
      undergoing percutaneous coronary revascularization, without increasing the risk
      of hemorrhage.

PMID- 9182213
TI  - Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV
      infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team.
AB  - BACKGROUND: Zidovudine has been the drug of choice for the initial treatment of
      symptomatic children infected with the human immunodeficiency virus (HIV). This
      trial was designed to assess the efficacy and safety of treatment with zidovudine
      alone as compared with either didanosine alone or combination therapy with
      zidovudine plus didanosine. METHODS: In this multicenter, double-blind study,
      symptomatic HIV-infected children 3 months through 18 years of age were
      stratified according to age (<30 months or > or =30 months) and randomly assigned
      to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end
      point was length of time to death or to progression of HIV disease. RESULTS: Of
      the 831 children who could be evaluated, 92 percent had never received
      antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim
      analysis (median follow-up, 23 months) showed a significantly higher risk of HIV
      disease progression or death in patients receiving zidovudine alone than in those
      receiving combination therapy (relative risk, 0.61; 95 percent confidence
      interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped
      and unblinded; the other two treatment arms were continued. At the end of the
      study, didanosine alone had an efficacy similar to that of zidovudine plus
      didanosine (median follow-up, 32 months) (relative risk of disease progression or
      death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A
      significantly lower risk of anemia or neutropenia was seen in patients receiving
      didanosine alone (P=0.036). CONCLUSIONS: In symptomatic HIV-infected children,
      treatment with either didanosine alone or zidovudine plus didanosine was more
      effective than treatment with zidovudine alone. The efficacy of didanosine alone
      was similar to that of the combination therapy and was associated with less
      hematologic toxicity.

PMID- 9182214
TI  - Infrarenal aortic aneurysms.

PMID- 9182215
TI  - Infrarenal aortic aneurysms.

PMID- 9182216
TI  - Infrarenal aortic aneurysms.

PMID- 9182217
TI  - Intracranial aneurysms.

PMID- 9182219
TI  - Intracranial aneurysms.

PMID- 9182218
TI  - Intracranial aneurysms.

PMID- 9182220
TI  - Intracranial aneurysms.

PMID- 9182221
TI  - A recombinant circumsporozoite protein vaccine against malaria.

PMID- 9182222
TI  - A recombinant circumsporozoite protein vaccine against malaria.

PMID- 9182223
TI  - A recombinant circumsporozoite protein vaccine against malaria.

PMID- 9182224
TI  - Kaposi's sarcoma after renal transplantation.

PMID- 9182225
TI  - Importance of colonic adenomas 5 mm or less in diameter.

PMID- 9182226
TI  - The folly of teaching-hospital mergers.

PMID- 9182227
TI  - The folly of teaching-hospital mergers.

PMID- 9182228
TI  - A gastric "bee-zoar".

PMID- 9182229
TI  - Meta-Analysis of Drug Abuse Prevention Programs. Proceedings of a meeting. July
      26-27, 1993.

PMID- 9182230
TI  - Comorbid Mental and Addictive Disorders: Treatment and HIV-Related Issues.
      Proceedings of a meeting. September 27-28, 1994.

PMID- 9182231
TI  - [Hepatitis c virus infection in dialysis: necessity of prevention and screening].

PMID- 9182232
TI  - [Kidney and nitric oxide].
AB  - Nitric oxide (NO) pathway is involved in various physiological and
      pathophysiological processes. NO is synthesised by NO synthase. Three isoforms,
      ecNOS, nNOS, iNOS have been identified to date, that are encoded by 3 distinct
      genes on chromosome 7, 12 and 17 respectively. L-arginine is likely involved in
      the control of NO synthesis. In the kidney, NO regulates glomerular hemodynamics
      by modulating the ultrafiltration coefficient and afferent and efferent renal
      arteriolar resistance. NO is further involved in the pressure-natriuresis
      mechanism and in the tubuloglomerular feedback. Several physiopathological models
      have underlined the importance of the NO in arterial hypertension and in
      glomerular inflammation.

PMID- 9182233
TI  - [Relative depletion in native vitamin D: a potential risk factor in Algerian
      hemodialysis patients with radiological evidence of hyperparathyroidism and
      osteomalacia independent of calcitriolemia].
AB  - Looser striae on the ischio-pubian branches and subperiosteal resorption of the
      phalanges were looked for in 113 chronic hemodialysis patients at the University
      Hospital of Annaba (Algeria) and were found in respectively 14 and 48 patients.
      Comparison of patients with and without radiological complications showed no
      significant difference in their age, sex ratio, nature of initial kidney disease
      and duration on dialysis. The patients with Looser striae had lower plasma levels
      of 25OHD3 than those without striae, whereas all other plasma parameters were
      similar. The plasma concentrations of intact PTH were higher in patients with
      resorption; these patients had lower plasma concentrations of calcium,
      bicarbonate, aluminum and 25OHD3 but similar plasma concentrations of phosphate
      and 1,25(OH)2D3. Multivariate analysis showed that PTH concentrations were
      independently linked only to plasma 25OHD3 (negatively) and duration on dialysis
      (positively). The results of this transversal study are in agreement with the
      well established pathophysiological roles of PTH hypersecretion, hypocalcemia and
      acidosis in the appearance of radiological hyperparathyroidism in hemodialysis
      patients. Furthermore they suggest that a relative native vitamin D deficiency
      may have a calcitriol independent role in favoring the occurrence of both
      osteitis fibrosa and osteomalacia.

PMID- 9182234
TI  - [Clinical significance of detection and quantification of hepatitis C virus RNA
      in hemodialysis: proposal for a rational diagnostic strategy].
AB  - Viral infections due to hepatitis C virus in hemodialysis patients are frequent
      and have a potential risk of progression towards chronicity. Biochemical and
      viral markers of infection, are transaminases level, anti-HCV serology and the
      detection of HCV RNA, respectively. A rational strategy based on routine use of
      these three diagnostic tools is proposed in order to avoid unnecessary assays and
      to increase in the case of health cost control, the cost/efficacy ratio. The
      latter is set up, in the sero-negative hemodialysed, on the early detection of
      infection by the hepatitis C virus in order to consider of a therapeutic which is
      able to cure patients and to avoid the ineluctable passage towards chronicity; in
      hemodialysed with positive HCV serology, the detection of HCV RNA allows to
      establish the infectiosity status of these hemodialysis patients. It is therefore
      very important to evaluate prospectively this diagnosis approach in hemodialysis
      patients.

PMID- 9182236
TI  - [Imaging of the renal parenchyma (apropos of the centenary of the discovery by
      Rontgen)].

PMID- 9182235
TI  - [Primary hyperoxaluria: Tunisian experience apropos of 24 pediatric cases].
AB  - We report on 24 children (10 girls) presenting with primary hyperoxaluria. The
      mean age at diagnosis was 6.3 years (range: 3 months-14.8 years). The mean
      interval between initial symptom and diagnosis was 1.3 year. The average follow
      up period was 22 months (range: 1-60 months). At the time of diagnosis the renal
      function was normal in 6 children, moderately altered in 1 and severely in 17.
      During the follow-up the renal function remained stable in 6 patients, improved
      in 2, deteriorated in 4. The 12 patients with end-stage renal disease at
      diagnosis remained unchanged. Urolithiasis were present in all patients older
      than 2 years, and in 1 among the 5 infants. Medullary nephrocalcinosis was
      observed in 3 patients in whom the renal function was preserved. Diffuse
      nephrocalcinosis was present in all patients with end-stage renal failure.
      Improvement of renal function was secondary to stone removal in 2 patients.
      Extracorporeal shock wave lithotripsy performed in 7 patients was efficient only
      in 3. In 10 patients oxalate bone disease was correlated with both renal function
      and dialysis duration, whereas retinal involvement noted in 6 patients was not.

PMID- 9182237
TI  - Special issue dedicated to Dr. Kinya Kuriyama.

PMID- 9182238
TI  - Comparative effects of the GABA uptake inhibitors, tiagabine and NNC-711, on
      extracellular GABA levels in the rat ventrolateral thalamus.
AB  - The primary mechanism by which the action of synaptically released GABA is
      thought to be terminated is by re-uptake into neurones and glial cells, and the
      pharmacological inhibition of this uptake may be beneficial in conditions where
      decreased GABAergic transmission has been implicated, such as epilepsy. We have
      compared the effects of two of these uptake inhibitors, tiagabine and NNC-711, on
      extracellular GABA levels in the thalamus of the rat, after both systemic and
      local administration. Both compounds produced dose-dependent increases in GABA
      concentration irrespective of the route of administration, but the concentrations
      required to produce increased extracellular GABA levels were considerably higher
      than those known to be effective for anticonvulsant purposes. These data suggest
      that, initially at least, alternative GABA transporters, not susceptible to
      inhibition by the compounds used, may still be able to remove synaptically
      released GABA from the extracellular space.

PMID- 9182239
TI  - Physicochemical and metabolic basis for the differing neurotoxicity of the
      pyrrolizidine alkaloids, trichodesmine and monocrotaline.
AB  - Monocrotaline and trichodesmine are structurally closely related pyrrolizidine
      alkaloids (PAs) exhibiting different extrahepatic toxicities, trichodesmine being
      neurotoxic (LD(50) 57 mu mol/kg) and monocrotaline pneumotoxic (LD(50) 335 mu
      mol/kg). We have compared certain physicochemical properties and metabolic
      activities of these two PAs in order to understand the quantitative and
      qualitative differences in toxicity. Both PAs were metabolized in the isolated,
      perfused rat liver to highly reactive pyrrolic dehydroalkaloids that appear to be
      responsible for the toxicity of PAs. More dehydrotrichodesmine (468 nmol/g liver)
      than dehydromonocrotaline (116 nmol/g liver) was released from liver into
      perfusate on perfusion for 1 hr with 0.5 mM of the parent PA.
      Dehydrotrichodesmine had a significantly longer aqueous half-life (5.4 sec) than
      that of dehydromonocrotaline (3.4 sec). In vivo, significantly higher levels of
      bound pyrroles were found in the brain 18 hr after injection of trichodesmine (25
      mg/kg; i.p.) than were seen following either an equal dose (25 mg/kg; i.p.) or an
      equitoxic dose (90 mg/kg; i.p.) of monocrotaline. Trichodesmine had a higher
      partition coefficient than monocrotaline for both chloroform and heptane,
      indicating its greater lipophilicity. The pK(a) of trichodesmine (7.07) was only
      slightly higher than that of monocrotaline (pK(a? 6.83), suggesting that a
      difference in degree of ionization was not a major factor affecting the relative
      ability of the dehydroalkaloids to cross the blood-brain barrier. We conclude
      that the greater lethality and neurotoxicity of trichodesmine compared to
      monocrotaline is due to two structural characteristics: (i) steric hindrance at
      position 14 of dehydrotrichodesmine results in greater resistance to hydrolysis,
      allowing more to be released from the liver and to be delivered to the brain;
      (ii) the larger isopropyl substituent at position 14 of dehydrotrichodesmine
      renders the molecule more lipophilic, leading to greater penetration of the
      brain.

PMID- 9182240
TI  - The gamma subunits of the native GABAA/benzodiazepine receptors.
AB  - Subunit-specific antibodies to all the gamma subunit isoforms described in
      mammalian brain (gamma(1), gamma(2S), gamma(2L), and gamma(3) have been made. The
      proportion of GABA(A) receptors containing each gamma subunit isoform in various
      brain regions has been determined by quantitative immunoprecipitation. In all
      tested regions of the rat brain, the gamma(1) and gamma(3) subunits are present
      in considerable smaller proportion of GABA(A) receptor than the gamma(2) subunit.
      Immunocytochemistry shows that gamma(1) immunoreactivity concentrates in the
      stratum oriens and stratum radiatum of the CA1 region of the hippocampus. In the
      dentate gyrus, gamma(1) immunoreactivity concentrates on the outer 2/3 of the
      molecular layer coinciding with the localization of the axospinous synapses of
      the perforant pathway. In contrast, gamma(3) immunoreactivity concentrates on the
      basket cells and other GABAergic local circuit neurons of the hilus. These cells
      are also rich in gamma(2S). In the cerebellum, gamma(1)++ immunolabeling was
      localized on the Bergmann glia. The gamma(2S) and gamma(2L) subunits are
      differentially expressed in various brain regions. Thus the gamma(2S) is highly
      expressed in the olfactory bulb and hippocampus whereas the gamma(2L) is very
      abundant in inferior colliculus and cerebellum, particularly in Purkinje cells,
      as immunocytochemistry, in situ hybridization and immunoprecipitation techniques
      have revealed. The gamma(2S) and gamma(2L) coexist in some brain areas and cell
      types. Moreover, the gamma(2S) and gamma(2L) subunits can coexist in the same
      GABA(A) receptor pentamer. We have shown that this is the case in some GABA(A)
      receptors expressed in cerebellar granule cells. These GABA(A) receptors also
      have alpha and beta subunits forming the pentamer. Immunoblots have shown that
      the rat gamma(1), gamma(2S), gamma(2L) and gamma(3) subunits are peptides of 47,
      45, 47 and 44 kDa respectively. Results also indicate that there are aging
      related changes in the expression of the gamma(2S) and gamma(2L) subunits in
      various brain regions which suggest the existence of aging-related changes in the
      subunit composition of the GABA(A) receptors which in turn might lead to changes
      in receptor pharmacology. The results obtained with the various gamma subunit
      isoforms are discussed in terms of the high molecular and binding heterogeneity
      of the native GABA(A) receptors in brain.

PMID- 9182241
TI  - Kinetic analysis of taurine influx into cerebral cortical slices from adult and
      developing mice in different incubation conditions.
AB  - The influx of taurine into cerebral cortical slices was studied with 3-day-old
      and 3-month-old mice in different ionic environments in incubation medium. In
      standard Krebs-Ringer medium the influx comprised two saturable uptake
      components, high- and low-affinity, and non-saturable penetration. In isoosmotic
      medium potassium stimulation abolished the high-affinity uptake in both age
      groups. In hyperosmotic medium the high-affinity uptake disappeared totally in 3
      day-old mice and partially in 3-month-old mice. The high-affinity uptake was also
      obliterated in hypoosmotic medium and in the absence of chloride ions in both age
      groups. The low-affinity uptake was abolished by potassium stimulation in 3-month
      olds and strongly inhibited in 3-day-olds. Hypoosmotic and chloride-free media
      also inhibited the low-affinity uptake at both ages. Non-saturable influx was
      greatly diminished in chloride-free media. The taurine uptake systems are thus
      strongly inhibited in incubation conditions which simultaneously evoke apparent
      release of taurine from cerebral cortical slices. This inhibition contributes to
      the magnitude of the estimated release, which in vitro represents overflow of
      released taurine molecules which escape recapture by the membrane carriers. In
      vivo the same mechanism may underlie the delayed and spreading neuromodulatory
      actions of taurine.

PMID- 9182242
TI  - Alkylation of [3H]8-OH-DPAT binding sites in rat cerebral cortex and hippocampus.
AB  - The binding of tritiated 8-hydroxy-2-(di-n-propyl-amino)tetralin, or [3H]8-OH
      DPAT, to membranes from rat cerebral cortex and hippocampus could be inhibited by
      serotonin (5-HT) and buspirone, and by the 5-HT antagonists propranolol, NAN-190,
      pindolol, pindobind-5-HT(1A), WAY1OO135, spiperone and ritanserin. All
      competition curves, except for ritanserin, best fitted a two-site model. In vitro
      treatment of the membranes with N-ethylmaleimide (NEM), to alkylate sulfhydryl
      groups, caused dose-dependent decreases of binding; the inhibition curves were
      biphasic, and the effects irreversible. Reduction of disulfide bonds with L
      dithiothreitol (L-DTT) also decreased binding, but in a monophasic way; these
      effects were fully reversible in cortex, but only partially reversible in
      hippocampus. In the latter region, but not in cerebral cortex, previous occupancy
      by [(3)H]8-OH-DPAT partially protected binding from the effects of both L-DTT and
      NEM, suggesting that the thiol groups in the receptor recognition site(s) of this
      brain region are readily accessible. The binding characteristics were examined
      with the aid of saturation curves, carried out with increasing concentrations, up
      to 140 nM, of [(3)H]8-OH-DPAT. The saturation data were suggestive of a two-site
      receptor model incorporating a high-affinity site (K(H) of 0.3-0.5 nM)
      corresponding to the 5-HT(1A) receptor, and a low-affinity site (KL of ca 25 nM).
      After in vivo alkylations, carried out by treating rats with N-ethoxycarbonyl-2
      ethoxy-1,2-dihydro-quinoline (EEDQ), the saturation curves from both control and
      EEDQ-treated rats were again best fitted to a two-site model. For EEDQ-treated
      animals, a drastic decrease of 5-HT(1A) receptor binding activity was noted; this
      loss was greater in hippocampus than in cerebral cortex. Since the decrease in 5
      HT(1A) receptors was not associated with changes in low-affinity binding, the
      results suggest independent regulations of the two [(3)H]8-OH-DPAT binding
      proteins. Altogether, the present data further supports the notion that [(3)H]8
      OH-DPAT, besides labelling 5-HT(1A) receptors, also binds to other structures in
      rat cerebral cortex and hippocampus.

PMID- 9182243
TI  - Dynamic modelling of the binding of substances to the conserved membrane-adjacent
      heptapeptide of the 15-residue C-terminal cytoplasmic fragment of mammalian
      dopamine D2 receptors.
AB  - Dynamic modelling was carried out on the binding in water of several substances
      to the conserved membrane-adjacent heptapeptide of the 15-residue C-terminal
      cytoplasmic fragment (C-tail) of mammalian dopamine D2 receptors,
      PheAsnIleGluPheArgLys. Particularly important in the establishment of binding
      pockets for ligands were the carboxyl, phenyl, guanidino, and epsilon-amino
      groups of the last 4 residues. A broad array of chemical structures was found to
      be potentially capable of binding to this site, among which were dopamine,
      dopamine D2 receptor agonists and antagonists, GABA, muscimol, GABA(B) receptor
      agonists and antagonists, homocamosine, and carnosine. Since the C-tail is
      critical for G protein binding, it is suggested that many naturally-occurring and
      synthetic substances may be modulators of activation of G proteins by G-coupled
      receptors.

PMID- 9182245
TI  - Immunohistochemical demonstration of GABAB receptors in the rat gastrointestinal
      tract.
AB  - Immunohistochemical localization of GABA(B)-receptors was demonstrated in the rat
      gastrointestinal tract using a monoclonal antibody (GB-1) raised against the
      purified GABA(B)-receptor. Immunoreactive staining for GABA(B)-receptors was
      found in some populations of endocrine, muscular and neuronal components in the
      stomach and gut wall. Positive mucosal epithelial, probably endocrine, cells were
      distributed throughout the stomach and intestine. Double immunostaining indicated
      that such positive cells for GABA(B)-receptors often co-possessed serotonin in
      the small intestine but not in the gastric body. In the muscular layer of the
      digestive canal, positive staining was seen as dotty granules punctuated on the
      surface of muscle fibers. In the enteric nervous system, positive neuronal somata
      were found in both submucosal and myenteric ganglia throughout the entire canal
      extending from the stomach to the rectum. This is the first report to visualize
      the cellular localization of GABA(B)-receptors in the gastrointestinal system of
      the rat, and should provide a fundamental basis for future studies on
      gastrointestinal functions regulated by GABA(B)-receptors.

PMID- 9182244
TI  - Differentiation by magnesium ions of affinities of nuclear proteins for consensus
      core nucleotide element of the transcription factor c-Myc in murine brain.
AB  - The addition of divalent cations such as Mg(2+) and Ca(2+) ions markedly reduced
      binding of a radiolabeled double stranded oligonucleotide probe for the
      transcription factor c-Myc in the presence of 100 mM KCl in nuclear extracts of
      the mouse whole brain. Irrespective of the addition of MgCl(2), binding was
      selectively competed with the unlabeled probe for c-Myc having a double stranded
      conformation. Treatment with V8 protease differentially modulated binding of the
      probe for c-Myc determined in the presence and absence of added MgCl(2).
      Introduction of irreversible covalent bonding between the radiolabeled probe and
      nuclear proteins led to retarded mobility of the radioactive probe/protein
      complex in the presence of MgCl(2) on sodium dodecyl sulfate electrophoresis
      regardless of treatment with DNase. However, an antibody against the c-Myc
      protein affected neither mobility nor intensity of the radioactive band on gel
      retardation electrophoresis. Moreover, regional distribution was different from
      each other in mouse brain when determined in the presence and absence of added
      MgCl(2). These results suggest that magnesium ions may have an ability to
      differentiate between nuclear c-Myc family proteins with different affinities for
      the consensus core nucleotide element CACGTG in murine brain.

PMID- 9182246
TI  - Cardiac alpha(1)-adrenoceptors that regulate contractile function: subtypes and
      subcellular signal transduction mechanisms.
AB  - Activation of alpha(1)-adrenoceptors as well as endothelin (ET) and angiotensin
      II (Ang II) receptors in cardiac muscle is coupled to acceleration of the
      hydrolysis of phosphoinositide (PI), with resultant production of inositol 1,4,5
      trisphosphate (IP(3)) and diacylglycerol. There is an excellent correlation
      between the extent of acceleration of the PI hydrolysis and the positive
      inotropic effect (PIE) under most experimental conditions after the
      administration of a-adrenoceptor agonists, ET and Ang II in the rabbit
      ventricular muscle. The PIE of the alpha-adrenoceptor agonists, ET and Ang II is
      associated with a negative lusitropic effect and an increase in the sensitivity
      of myofilaments to Ca(2)+ ions. The PIE can be selectively inhibited by
      inhibitors of protein kinase C (PKC) such as staurosporine, NA 0345 and H-7, with
      little effect on the PI hydrolysis and the PIE of isoproterenol and Bay k 8644.
      Surprisingly, an activator of PKC, phorbol 12,13-dibutyrate (PDBu), selectively
      and more completely inhibited the PIE and acceleration of PI hydrolysis induced
      by the alpha-adrenoceptor agonists as well as by ET and Ang II in the rabbit.
      These receptor agonists consistently cause intracellular alkalinization by
      activation of Na+-H+ exchange, while the effects on membrane ion channel
      activities are divergent. For example, alpha-adrenoceptor agonists cause
      monophasic prolongation of the action potential, the time course of which
      coincides well with that of the PIE, while ET and Ang II produce a biphasic
      change in action potential duration, i.e., the long-lasting prolongation preceded
      by a transient abbreviation. Alpha-adrenoceptor agonists scarcely affect I(ca),
      whereas ET elicits a biphasic alteration of the current. In addition, the
      potassium current, I(K1), is markedly suppressed by alpha-adrenoceptor agonists,
      but this effect is not revealed with Ang II under the same experimental
      condition. These results indicate that the effects of alpha(1)-adrenoceptor
      stimulation are partially shared by those of FT and Ang II receptor activation in
      the heart. Approximately 60% of the total population of alpha(1)-adrenoceptors in
      the rabbit ventricle are composed of alpha(1A) subtype, which is susceptible to
      chlorethylclonidine (CEC) and is predominantly responsible for the alpha(1)
      mediated PIE and PI hydrolysis. The remaining fraction that belongs to alpha(1A)
      subtype is further subclassified into the WB 4101-sensitive (partly coupled to PI
      hydrolysis) and the niguldipine-sensitive (PI hydrolysis-unrelated) subtypes.

PMID- 9182248
TI  - Reserpine-induced immunocytochemical change of neuropeptide Y in the hypothalamic
      arcuate nucleus.
AB  - The effect of reserpine on neuropeptide Y immunoreactive (NPY-IR) neurons in the
      rat hypothalamic arcuate nucleus was examined by immunocytochemical techniques.
      Although only NPY-IR fibers and terminals were distributed in this nucleus in
      untreated and saline treated rats, single treatment of reserpine (10 mg/kg, i.p.)
      visualized abundant NPY-IR neuronal cell bodies: the increase began at 12 h of
      postinjection, reached its maximal level at 48 h, and returned to its normal
      level at 96 h. Pretreatment of nialamide, a monoamine oxidase inhibitor,
      prevented these acute reserpine-induced changes, suggesting reserpine acts on NPY
      neurons through monoaminergic mechanism. Chronic treatment of haloperidol (5
      mg/kg, once daily for 5 days) a dopamine receptor antagonist, could induce the
      similar increase of NPY immunoreactivity. However, interruption of adrenergic and
      serotonergic neurotransmissions by chronic treatment of propranorol and
      methysergide, or chemical lesions of ascending noradrenergic and serotonergic
      pathways by 6-hydroxydopamine and 5,6-dihydroxytryptamine, could not induce any
      immunoreactive increase of NPY in arcuate neurons. These findings strongly
      suggest that reserpine-induced NPY increase occurs through dopaminergic afferents
      in hypothalamic arcuate neurons.

PMID- 9182247
TI  - Neuron-specific expression of a chicken gicerin cDNA in transient transgenic
      zebrafish.
AB  - Gicerin, a novel cell adhesion molecule which belongs to the immunoglobulin
      superfamily, is expressed temporally and spatially in the developing chick brain
      and retina. The previous in vitro experiments using transfected cells showed that
      gicerin can function as a cell adhesion molecule which has both homophilic and
      heterophilic binding activities. For the in vivo analyses of gicerin in neural
      development, we tried to utilize a zebrafish system, a vertebrate suitable for
      studying early development. We generated transient transgenic animals by
      microinjecting DNA constructs into zebrafish embryos. Chicken gicerin, under
      control of the neurofilament gene promoter, was preferentially expressed in
      neuronal cells and gicerin-expressing neurons exhibited a fasciculation formation
      with neighboring gicerin-positive axons, which may be partly due to homophilic
      cell adhesion activity of gicerin. These experimental results suggest that this
      fast and efficient transgenic animal system is useful for studying the functional
      roles of neuron-specific genes during the development.

PMID- 9182249
TI  - GTP cyclohydrolase I gene, tetrahydrobiopterin, and tyrosine hydroxylase gene:
      their relations to dystonia and parkinsonism.
AB  - Catecholamine biosynthesis is regulated by tyrosine hydroxylase (TH) requiring
      tetrahydrobiopterin (BH4) as the cofactor. We found four (human TH type 1-4) and
      two isoforms (TH type 1 and 2) in humans and monkeys, while non-primate animals
      have a single TH corresponding to human TH type 1. BH4 is synthesized from GTP,
      and GTP cyclohydrolase I (GCH) is the first and regulatory enzyme. Mutations in
      GCH gene were found to cause both GCH deficiency with autosomal recessive trait
      and hereditary progressive dystonia with marked diurnal fluctuation (HPD)
      (Segawa's disease)/or DOPA-responsive dystonia (DRD) with autosomal dominant
      trait. When GCH activity is decreased to less than 20% of the normal value, the
      activity of TH in the nigrostriatal dopaminergic neurons may be first decreased
      resulting in decreases in TH activity and dopamine level, and in the symptoms of
      HPD/DRD. In contrast to HPD/DRD, juvenile parkinsonism (JP) have normal GCH
      activity. In Parkinson's disease (PD), GCH, TH, and dopamine in the striatum may
      decrease in parallel, as the secondary effects caused by cell death.

PMID- 9182250
TI  - Amine precursor amino acid therapy: from neurochemical basis to clinical aspects.
AB  - The particulars regarding the amine precursor therapy for treatment of
      neuropsychiatric disorders and their neurochemical background are described
      historically. Furthermore, peculiar or artificial amino acids which are
      metabolized into the brain amine or their derivatives and promised their clinical
      application are also introduced.

PMID- 9182251
TI  - The occurrence of protein kinase C theta and lambda isoforms in retina of
      different species.
AB  - The localization and immunochemical identification of the novel protein kinase C
      theta (nPKC theta) and the atypical protein kinase C lambda (aPKC lambda)
      isoforms in retinas of different species were analyzed by immunohistochemistry
      and SDS-PAGE/Western blotting. nPKC theta immunoreactivity is associated with
      bipolar cells of mammalian (rabbit, rat and guinea pig) retinas but not the non
      mammalian goldfish retina which has a lower concentration of nPKC theta. However,
      SDS-PAGE and Western blotting data indicate the antigen recognized by the nPKC
      theta monoclonal antibody in the retina is of a lower molecular weight than that
      expected for nPKC theta. This would suggest nPKC theta is more susceptible to
      degradation/breakdown than other PKC isoforms found in the retina or that the
      nPKC theta antibody may be recognizing an unknown retinal antigen. A comparison
      of nPKC theta and cPKC alpha immunoreactivities in bipolar cells shows unique
      distributions exist for the two isoforms. nPKC theta is present in the developing
      retina at an earlier stage than cPKC alpha. The typical 'transport' of cPKC alpha
      toward axonal terminals by phorbol-12,13-dibutyrate does not occur for nPKC theta
      yet both are translocated from the cytosolic to membrane compartments. The inner
      plexiform layer and the inner nuclear layer (putative horizontal cells) of all
      species examined (rabbit, rat, guinea pig and goldfish) exhibited positive
      immunoreactivity for aPKC lambda as confirmed by SDS-PAGE/Western blotting.

PMID- 9182252
TI  - Effect of K+- and kainate-mediated depolarization on survival and functional
      maturation of GABAergic and glutamatergic neurons in cultures of dissociated
      mouse cerebellum.
AB  - The effect of the depolarizing agents, an elevated potassium concentration (25
      mM) or kainic acid (50 microM) on neuronal survival and differentiation was
      investigated in cultures of dissociated neurons from cerebella of 7-day-old mice.
      When maintained in the presence of an antimitotic agent such cultures consist
      primarily of glutamatergic and GABAergic neurons. Cell survival was monitored by
      measurement of DNA, and differentiation by determining uptake and depolarization
      coupled release of glutamate (D-aspartate as label) and GABA. The depolarizing
      agents were added separately or together either from the start of the culture
      period (7-8 days) or at day 5 in culture. The main findings are that K+
      depolarization is important for differentiation of glutamatergic neurons but not
      for GABAergic neurons. This depolarizing signal is important during the early
      phase of development in culture. For glutamatergic neurons, kainate may replace
      K+ as a depolarizing signal whereas in case of the GABAergic neurons, kainate was
      toxic particularly during the late phase of development. It was further observed
      that the glutamatergic neurons when maintained in a medium with 5 mM K+ during
      the first 5 days in culture became sensitive to kainate toxicity when this amino
      acid was added at day 5. This was not the case when the medium contained 25 mM K+
      from the start of the culture period.

PMID- 9182253
TI  - Heterogeneity of tachykinin receptors in the rabbit lung.
AB  - The tachykinins, substance P (SP) and neurokinin A (NKA), are agonists for the
      NK(1) and NK(2) receptors, respectively. Tachykinins have various respiratory
      effects, including bronchoconstriction. This study characterizes tachykinin
      binding sites in the rabbit lung. We hypothesize that (2
      [(125)I]iodohistidyl(1))Neurokinin A ([(125)I]NKA) interacts with NK1 and NK2
      binding sites in the rabbit lung. The K d determined from saturation isotherms
      was 0.69 times/divided by 1.14 nM (geometric mean times/divided by SEM) and the B
      max was 4.15 + or - 0.22 femtomole/mg protein (arithmetic mean + or - SEM).
      Competitive inhibition studies with NKA, SP and various selective tachykinin
      agonists showed the rank order of potency; [beta-Ala(8)]-Neurokinin A 4-10 = SP
      >> NKA >> [Sar(9),Met(02)11]-Substance P. [beta-Ala(8)]-Neurokinin A 4-10, a
      selective NK(2) agonist, and SP inhibition of [(125)I]NKA binding were best
      described using a two-site model. Competitive inhibition studies using the
      selective nonpeptide NK(2) antagonist (SR 48968) and the selective nonpeptide
      NK(1) antagonist (CP 96,345) revealed Ki's of 5.5 nM and 8.1 nM, respectively.
      Our data therefore suggest that [(125)I]NKA binds to both the NK(1) and NK(2)
      receptors in the lung.

PMID- 9182254
TI  - High levels of extracellular glutamate are present in retina during neonatal
      development.
AB  - The three major classes of neurons which comprise the primary visual pathway in
      retina are glutamatergic. These cells are generated in two separate developmental
      stages, with one subclass of photoreceptors (cones) and ganglion cells generated
      before birth; and the other subclass of photoreceptors (rods) and bipolar cells
      generated during the first week after birth. Gas chromatography/mass spectroscopy
      analysis coupled with a new method for collecting small samples of extracellular
      fluids from retina were used to determine the levels of endogenous glutamate
      present during differentiation and synaptogenesis of these different cell types.
      As expected the total retinal content of glutamate increased during the postnatal
      period in synchrony with the generation and maturation of glutamatergic cells.
      However, a significant proportion of the endogenous pool was found
      extracellularly at birth. Intracellular glutamate is localized within cell bodies
      and growing processes of cones and ganglion cells at this time but few
      glutamatergic synapses are present. The extracellular concentration of glutamate
      actually declined during the most active period of synaptogenesis, reaching very
      low levels in the adult. The high concentrations of extracellular glutamate in
      neonatal retina could play an important role in a variety of developmental events
      such as dendritic pruning, programmed cell death and neurite sprouting.

PMID- 9182255
TI  - [Increase of oxygen free radicals and their derivatives in chemo- and radiation
      treated neoplasm patients].
AB  - BACKGROUND: Radical oxygen species (ROS) are known to mediate cytotoxic
      anticancer activity by modifying the cellular homeostatic redox balance. The aim
      of the study is to evaluate whether cancer patients show more ROS after
      radio/chemotherapy. METHODS: ROS were evaluated in 32 oncologic untreated
      patients. Blood samples were collected both before and after the end of
      radio/chemotherapy. Spectrophotometric detection of ROS was performed by using d
      ROMs test (Diacron). RESULTS: After therapy all patients showed a marked increase
      in ROS (378 +/- 35 U Carr) compared to values measured before therapy (269 +/- 62
      U Carr, p < 0.0001). This result was more evident during the first course of
      therapy. No significant differences were observed between patients who received
      radio or chemotherapy. CONCLUSIONS: In conclusion both radio and chemotherapy
      induce oxidative stress by increasing radical oxygen species, exceeding the
      antioxidative capacities of cancer patients. This is useful for therapeutic
      purposes but may enhance the cytotoxicity induced by therapy.

PMID- 9182256
TI  - [The "rapidity" factor in the specific immunity response after oral vaccination].
AB  - The vaccination per os induces early, specific immunoglobulinic responses in
      intestine, saliva, bile and urine, as well as in the respiratory apparatus,
      involving above all sIgA, but also IgG and IgM. The notion of the rapidity of the
      specific immunitary responses constitutes an important acquisition at
      immunological level (mechanisms of the antibody-poiesis) and, also, from the
      therapeutic and analytical point of view. The use of oral vaccines is fully
      justified by the rapidity of the immune reactions not only at enteric level, but
      also in the different districts of the animal organisms (gingives, saliva,
      biliary, urinary and respiratory tract). The availability of immunizing agents is
      a remarkable occurrence from the clinical point of view, in that the non rare
      failure of the chemo-antibiotic-therapy are a common knowledge. Its far
      prophylaxis, also, the rapidity of action of the oral vaccines is very important;
      in the case of parenteral vaccination, instead, a latency time of about a week is
      necessary. The rapidity of the immune responses after oral immunization give an
      evaluation of the immunizing activity of antigenic formulations in a short time,
      with evident advantages in the point both of a scientific and economic view.
      Moreover, it is possible to perform the quali-quantitative analysis of vaccinal
      preparations in a few of days.

PMID- 9182257
TI  - [Vascular "remodeling"].
AB  - Vascular remodeling means a specific organization of the vascular wall around a
      diminished lumen as to the before existing conditions, with consequent vascular
      geometry modification. This organization comes from the response of all vascular
      components (endothelium, muscular cells, connective component, etc.) to physical
      and chemical stimuli. Particular behaviour of the vascular wall has lately been
      pointed out, both in long known pathologies (arteriosclerosis, arterial
      hypertension, diabetes mellitus, arteriosclerotic aneurysms) and in situations
      involving both physiopathology (ischaemia-reperfusion, angiogenesis) as therapy
      (angioplasty).

PMID- 9182258
TI  - [The concept of quality of life in cardiac failure].
AB  - Chronic congestive heart failure is a common yet devastating syndrome and is a
      leading cause of morbidity and mortality in the industrialised countries. The
      incidence and prevalence of chronic congestive heart failure is increasing,
      placing a growing burden on the health care system. Despite many advances in
      treatment for heart disease, chronic heart failure is a terminal condition with a
      death rate as high as that for many malignant tumours. Patients suffering from
      chronic congestive heart failure report a poor quality of life because of
      physical symptoms, functional disability, emotional and economic burdens,
      frequent hospitalisations, and poor prognosis. In the context of heart failure,
      mortality risk (prognosis quoad vitam) can be measured using a variety of
      physiological variables; left ventricular (LV) dysfunction plays a primary role
      in the pathogenesis of congestive heart failure and correlates with prognosis,
      but a strong quantitative relation between exercise performance and indexes of LV
      function has not been demonstrated. This finding underscores the importance of
      psychosocial interventions in improving the quality of life and care outcomes for
      patients with heart failure. For this reason, questionnaires of quality of life,
      assessed by direct patient self-reports, have recently been imposed in
      cardiology, they have been used specially for evaluating most treatment of
      cardiac failure. The refinement of a definition of quality of life improved
      methods to study quality of life will contribute to a better understanding of
      this complex concept in heart failure patients.

PMID- 9182259
TI  - [Melkersson-Rosenthal syndrome. Presentation of a clinical case and review of the
      literature].
AB  - Melkersson-Rosenthal syndrome is a rare form of hereditary angioedema
      characterised by a triad of symptoms of which incomplete (oligo- or
      monosymptomatic) forms have been described, frequently associated with
      dysreactive diseases or neoplasia. The authors describe the case of a 48-year-old
      man with an incomplete form which was successfully treated with steroids and,
      after a careful and detailed revision of the literature on the subject, they make
      a number of etiopathogenetic, histopathological, clinical and therapeutic
      comments.

PMID- 9182260
TI  - [Amyotrophic lateral sclerosis in a patient with Waldenstrom's
      macroglobulinemia].
AB  - Although a peripheral neuropathy is the best known neurological complication of
      Waldenstrom's Macroglobulinemia (WM), the association of Amyotrophic Lateral
      Sclerosis (ALS), or other Motor Neuron Diseases (MND) with monoclonal
      gammopathies is described. We report the case of a male patient (41 years old)
      with WM and ALS. Whether monoclonal gammopathies play a role in the pathogenesis
      of MND is unclear but is la possible that patients might have antibodies against
      motor neurons. In our reported case neurologic symptoms were the first and the
      most important manifestations of the underlying hemopathy and despite
      plasmapheresis and immunosuppressive treatment ALS syndrome progressed. The
      neurologic disease worsened despite the improvement of WM.

PMID- 9182261
TI  - Junctional tachycardia.

PMID- 9182262
TI  - Stroke rehabilitation. Salvaging ability after the storm.

PMID- 9182263
TI  - Anatomy of a dental malpractice case: the trial.

PMID- 9182264
TI  - There is reason to hope... and organized dentistry provides it.

PMID- 9182265
TI  - [Mesangiocapillary glomerulonephritis].
AB  - Mesangiocapillary glomerulonephritis (MCGN) accounting for 15 percent of adult
      glomerulopathy has not received proper attention in the Hungarian medical
      literature. The present study offers a detailed description of the procedures to
      be used for distinguishing its three types, which is only possible by
      histological, mainly electron microscopic examination of kidney biopsy samples.
      Type I represents subendothelial deposits; Type II is the "sausage-like" dense
      deposits localised on the lamina densa of the glomerular basal basement membrane;
      Type III is the mixed type. There is no significant difference in their clinical
      appearance. They occur most frequently as "coloured nephrosis" (the syndrome of
      nephrosis is associated with haematuria and/or hypertension). The course of the
      disease is characterised by periodicity, and in 50 percent of the cases kidney
      failure may develop. The therapy for MCGN has not been established. The
      administration of steroid, cyclophosphamide and anticoagulant can have a
      favourable effect.

PMID- 9182266
TI  - [Significance of ST segment and R wave changes in exercise-induced
      supraventricular extrasystole].
AB  - In a retrospective study the importance of ST segment and R wave changes in sinus
      beats and in supraventricular extrasystoles was examined in 23 patients who had
      exhibited supraventricular extrasystoles during exercise testing and who had
      undergone coronary arteriography in 1993 and 1994. Significant coronary artery
      disease was detected in 18 patients (group A), whereas 5 subjects (group B) had
      no demonstrable obstructive lesions. In every patient the authors measured the ST
      depression and R wave amplitude of the supraventricular extrasystole (STe and Re,
      respectively), and of the preceding sinus beat (STs and Rs, respectively), and
      than they calculated the difference between the two [ST(e-s) and R(e-s),
      respectively]. The ST(e-s) + R(e-s) value was higher than zero mV in 13 patients
      in group A, and in neither case in group B. Among the 4 patients in group A with
      false negative results of exercise tests, 3 had a positive ST(e-s) + R(e-s)
      value, whereas the only patient in group B with false positive exercise test
      result had a negative ST(e-s) + R(e-s) value. In patients with exercise induced
      supraventricular extrasystoles, the changes of ST depression and R wave amplitude
      in the extrasystoles and in the preceding sinus beats, may supplement the
      criterions of a positive examination.

PMID- 9182267
TI  - [Resuscitation of neonates in the delivery room. Recommendations by the American
      Heart Association and American Academy of Pediatrics].
AB  - According to the recommendation of the American Heart Association and the
      American Academy of Pediatrics 43 newborn babies with mean birth weight 3300 g
      (range 610-5100 g) were resuscitated. One-minute Apgar score was 0:1, 1:22, 2:11,
      3:7, 4:2 cases. Mask and bag ventilation were needed in 43, heart compression in
      7, tracheal intubation in 2, drugs in 2 cases. Five-minute Apgar values were
      8:39, 5:1, 7:1 case. All resuscitations were successful. The resuscitation
      program is a great advance in the field of neonatology. Nationwide application of
      it might be helpful to decrease neonatal mortality in Hungary.

PMID- 9182268
TI  - [Certain specific aspects of fear of death].
AB  - The question of death is a taboo all over the world. Issues related to it (fear
      of death, mourning-reactions etc.) are rarely discussed even between medical
      doctors. The fact that the majority of the authors doesn't differentiate between
      the problems when dealing with them (e.g. fear of own, or other person's death)
      plays an important role in the theoretical and empirical contradictions of death
      topic. The special literature give particularly little attention to fear of death
      concerning suicide what makes the judgement of the problem of fear of death even
      harder in the contradictory attitudes of medical doctors towards death.

PMID- 9182269
TI  - [Isolated metastasis in the gallbladder from malignant cutaneous melanoma
      discovered by ultrasound].
AB  - The authors describe the metastasis in gallbladder of the malignant melanoma
      removed from dorsal skin. Due to the increasing incidence of dermal melanomas,
      they emphasize the occurrence of unexpected and unpredictable metastases and the
      need for a close, life-long follow-up of patients. The prognosis of visceral
      metastases is affected to a great extent by their early detection.

PMID- 9182270
TI  - [Earliest Hungarian reaction to X-rays].

PMID- 9182271
TI  - [Fossils of auditory ossicles from the distance of one and a half millenia].

PMID- 9182272
TI  - [Change of trend in the treatment of type 2 non-insulin-dependent diabetics].
AB  - Medical opinion about the significance of non-insulin-dependent diabetes has been
      recently changed for three reasons: epidemiological evidence about the
      continuously increasing disease-prevalence, accumulation of new intriguing
      details on the pathophysiology of the disease, and the growing clinical evidence
      about the importance of accelerated atheromatosis related to any stage of the
      disease. The new theoretical approach resulted in some new aspects of
      therapeutical management as well. There is an emphasis on the early recognition,
      the very strict metabolic control and the individualized form of the therapy.
      Well organized regular medical care for the diabetics, recognition and effective
      treatment of comorbidities (dyslipidemia, high blood pressure), self-involvement
      of the patients in the management (ie. patient education) are the corner stones
      of this approach. The authors give a short review about the armamentura of the
      therapy available nowadays, including rules of indication for different
      sulfonylurea drugs, combined sulfonylurea-insulin treatment and single insulin
      regimes as well.

PMID- 9182274
TI  - [Management of postoperative ischemic jejunal stenosis using balloon dilatation
      and/or Wallstent implant].
AB  - Ischaemic stenosis of the jejunum is rare. For technical, anatomical, and
      pathological reasons ischemic stenosis of the jejunal segment used for the
      replacement of the stomach and oesophagus requires a special approach. The
      present study reports two cases of dilation of ischaemic strictures of the
      jejunal loop by balloon catheter, used for replacement after oesophagogastrectomy
      and gastrectomy. In the later case, in which the occlusion of the blood vessels
      supplying the affected segment was observed right at the level of the aorta,
      Wallstent was implanted. The advantages and disadvantages of metal stents are
      discussed and oesophaogoaortic fistula, a rare complication, which appeared a
      year after Wallstent placement, is described. The two cases presented in this
      study give evidence that using balloon catheters and implanting Wallstent-in
      selected cases-may give good results in the management of postoperative ischaemic
      strictures of the jejunum. The minimally invasive technique with the special
      indications described here is not known to have been used so far. The rare
      complication mentioned, however, requires special attention.

PMID- 9182273
TI  - [Hematologic abnormalities in pulmonary tuberculosiss].
AB  - This study surveys the extent and severity of haematological abnormalities which
      occurred in 380 patients with pulmonary tuberculosis. Full blood count, bone
      marrow aspiration smears, and bone marrow trephine biopsy was analyzed by
      authors. Anaemia was present in 32 percent of patients. Leucocytosis with
      neutrophilia occurred in 18 percent. Leucopenia with neutropenia, and lymphopenia
      was observed in 16 percent in patients with very severe clinical tuberculosis.
      Elevated platelet count occurred in 8 percent with deep vein thrombosis in legs
      in 50 percent. Dysmyelopoietic syndrome was diagnosed in one case by bone marrow
      trephine biopsy. There was a close correlation between the haematological
      abnormalities and the severity of clinical findings of pulmonary tuberculosis.
      This survey has revealed that haematological abnormalities are relatively common
      in severe pulmonary tuberculosis. It seems that body weight loss, white blood
      cell count, haemoglobin level and erythrocyte sedimentation rate are useful
      indices of severity of the tuberculosis. The return of these indices to a normal
      level is a good indication of disease control in that they correlate with sputum
      conversion to acid-fast bacilli negative.

PMID- 9182275
TI  - [Prenatal diagnosis of hemophilia B].
AB  - The authors are reporting on the prenatal diagnosis of the X-linked haemophilia B
      for the first time in Hungary applying the polymerase chain reaction. DNA
      sequence containing a HhaI restriction endonuclease site close to the factor IX
      gene was amplified using polymerase chain reaction. The products from polymerase
      chain reaction were detected on polyacrylamide gel with ethidium bromide staining
      after the digestion with HhaI restriction enzyme. In the first step of the
      diagnosis DNA specimen was prepared from chorion derived from a 11th week
      gestation of haemophilia B carrier mother. The investigation of fetal DNA proved
      a male fetus. The detection of HhaI polymorphism of the fetus demonstrated the
      inheritance of the disease causing allele. The parents asked for the termination
      of pregnancy based on the result.

PMID- 9182276
TI  - [Surgical management of masculine trassexualism].
AB  - The authors report on the first Hungarian case of sex-transforming operation.
      They present details of the social history and management of their case leading
      up the decision for surgery. Preoperative assessment and medication, operation
      technique and postoperative care are also described in detail. The case report
      highlights the difficult ethical and legal issues which have to be considered
      when such surgery is requested. Following a series of in-depth psychological,
      gynaecological, urological and forensic consultations that had been carried out
      in order to be convinced about the patients's determination for undergoing sex
      transforming operation, the authors were granted legal and professional license
      by the Hungarian Medical Research Council to carry out the procedure. Two years
      after the operation, the patient commented on her full satisfaction with the care
      he had received.

PMID- 9182277
TI  - [Interaction between prajmaline and metoprotol: a possible pharmacogenetic
      explanation].

PMID- 9182278
TI  - [Can we talk about overconsumption of vitamins, minerals and trace elements?].

PMID- 9182279
TI  - [Alternatives to heart transplantation].
AB  - This paper is about the alternatives of curing the drug-refractory heart failure
      with the exception of cardiac transplantation. It includes even the newest
      methods mostly being in the phase of animal experiment in the meantime. The
      authors give a review on the different possibilities of skeletal muscle
      autotransplantation for cardiac support, such as cardiomyoplasty which has
      already been done in Hungary too, externally powered mechanical devices for long
      term support, molecular and cellular cardiomyoplasty. The partial ventriculectomy
      and transmyocardial laser revascularization are mentioned as well. Although, most
      part of the enumerated procedures is not available in Hungary at this time, they
      are expected to enter the arsenal of medicine in the future.

PMID- 9182280
TI  - [Risk factors of infected pancreatic necrosis, its microbiology and antibiotic
      treatment].
AB  - Acute pancreatitis is associated with greater and smaller necrosis in 20% of the
      cases. The lethality rate of sterile and infected necrosis is 10 and 15-40%,
      respectively. The results of a retrospective and a prospective study in acute
      pancreatitis have been analyzed in this study. Twenty patients suffering from
      infected necrosis due to acute necrotising pancreatitis were selected into the
      retrospective study. They were divided into two groups: Group 1 (N = 10)
      survivors, Group 2 (N = 10) those who died. The fate of patients was determined
      by their age, the severity of pancreatitis, and the effectiveness of the
      operation. In a prospective study 63 patients were operated due to benign
      pancreatic disease with fluid collection. Microbiological samples were taken
      during surgery in every case. It could be stated that the Enterobacteriaceae spp.
      play the principal role in the infection, and the anaerobic bacteria occur
      sporadically. The omission of bacteriological sample taking during surgery
      frustrates the targeted antibiotic treatment. The blood culturing may have useful
      contribution. The targeted antibiotic therapy based on relevant microbiological
      sample taking is substantial complementary of the surgical intervention in the
      treatment of the inflammatory pancreatic diseases.

PMID- 9182281
TI  - [Treatment of atopic dermatitis].
AB  - The authors give a survey of the treatment of atopic dermatitis with respect to
      its extent and severity. Our knowledge about the immunopathology of the disease
      altered during the past years and thus it was possible to use new medicines. The
      most important one among them is Cyclosporin A, which is a selective
      immunosuppressive drug. It effectively decreases the symptoms of atopic
      dermatitis by blocking T cells which were already activated. Because of the
      serious side-effects of Cyclosporin A (nephrotoxicity, hypertension) it can only
      be applied when no other local or systemic treatment proves to be effective. Even
      a short application of the medicine improves not only the quality of patient's
      life but also the long-term outcome of the disease.

PMID- 9182282
TI  - [Detection of t(14;18) chromosome translocation in follicular lymphoma by
      polymerase chain reaction].
AB  - In most cases of centroblastic/centrocytic follicular lymphomas the bcl-2 proto
      oncogene (18q21) is translocated to the immunoglobulin JH region of chromosome 14
      (14q32). About three quarters of the translocations are concentrated on the 3'
      nontranslated, a few hundred basepare-long region of bcl-2, the so called major
      breakpoint region (mbr), the remaining 20-25% is located about 30 kilobases
      downstream of bcl-2 coding sequences in the minor cluster region (mcr). The
      majority of the immunoglobulin breakpoints can be found in JH6-4 genes. The
      polymerase chain reaction method can detect the translocation already in a very
      few number of cells (> 10(3)). This very sensitive technique makes it possible to
      detect the translocation in lymphoid/lymphoma of peripheral blood and bone marrow
      that are missed by other diagnostic methods. This way one can perform a quick,
      early diagnosis, examine the result of treatments as well as detect the
      remissions and the possible relapses right at the beginning. All the advantages
      of this method contribute to a more successful treatment of follicular lymphoma.
      This present work describes a polymerase chain reaction technique which is
      capable of a detection of the t(14;18) translocation in a patient of
      centroblastic/centrocytic lymphoma, moreover shows how this translocation
      disappears after 4 week of radiotherapy of the patient.

PMID- 9182283
TI  - [Postoperative percutaneous endoscopic gastrostomy/jejunostomy].
AB  - In order to cure complications appeared in the postoperative period two patients
      were treated with percutaneous endoscopic gastrostomy/jejunostomy (PEG, PEGJ)
      with the purpose of long-lasting enteral feeding and decompression. The
      indications of PEG/PEGJ were the following: external gastric fistula in one case
      and anastomotic leakage in one case. In the patients the PEG was located by
      intraoperative X-ray examination, this method was not published earlier.
      Regarding complications of the early postoperative period the PEG and the PEGJ
      are considered useful and expedient procedures with the aim of lasting enteral
      feeding and decompression.

PMID- 9182284
TI  - [Basis of health culture in Hungary].

PMID- 9182285
TI  - Conduct you own American Board of Pediatric Dentistry site visit!

PMID- 9182286
TI  - Expression of sialyl-Tn in breast cancer. Correlation with prognostic parameters.
AB  - To investigate the expression of a simple mucin-type carbohydrate antigen (Sialyl
      Tn/STn) and its putative relationship with established or potentially useful
      clinico-pathologic prognostic parameters in breast cancer, we studied forty-six
      cases of invasive breast carcinoma in formalin-fixed, paraffin-embedded tissue
      sections. STn antigen was detected by the HB-STn antibody using an avidin-biotin
      peroxidase method. The parameters studied were tumour size, histologic grade,
      nodal status, proliferative index (with MIB-1), ER expression, ploidy, c-erbB-2
      and p53 expression. STn expression was observed in 18 cases (39%) of breast
      cancer. The expression of STn was associated with axillary node metastasis, ER
      negativity and c-erbB-2 expression. A tendency towards an association between STn
      immunoreactivity and high histologic grade was also found. No correlation was
      observed between STn immunoreactivity and age, tumour size, proliferative index,
      ploidy and p53 expression. We conclude that the detection of STn immunoreactivity
      may be useful for predicting the likelihood of lymph node metastasis and that the
      outcome of patients with breast cancer should be further investigated in order to
      find whether or not the data of the present study are confirmed in larger series.

PMID- 9182287
TI  - Breast hamartoma with invasive ductal carcinoma. Report of two cases and review
      of the literature.
AB  - Two cases of well-defined masses also containing clinical and radiographical
      abnormalities suggestive of malignancy, subsequently found to be invasive ductal
      carcinomas in breast hamartomas are described. The patients were 53 and 78 years
      old. Both presented with a generally soft palpable breast lump, containing a firm
      area which in one case invaded and ulcerated the skin. Mammography demonstrated
      two typical hamartomas: one containing a spiculated opacity, the other irregular
      opacities with suspicious calcifications, suggesting the presence of carcinomas
      in these benign lesions. The cut surface of these well-circumscribed masses
      measured 5 cm and 7 cm. The microscopic appearance was characteristic of breast
      hamartoma (sharp circumscribed "pseudocapsule" surrounding breast fibrocystic
      changes with variable amounts of adipose tissue) with the firm area in each case
      corresponding to invasive ductal carcinoma. In one case the invasive ductal
      carcinoma was confined to the hamartoma, whereas in the other malignant tumor,
      cells extended beyond the surrounding breast tissue and infiltrated the skin.
      These findings raise the question of secondary involvement of a hamartoma by
      invasive carcinoma. Breast hamartomas are probably underrecognized lesions. In
      our view, these findings do not justify a more aggressive approach towards the
      management of breast hamartomas.

PMID- 9182288
TI  - Overexpression of the 67 kD laminin receptor correlates with the progression of
      gastric carcinoma.
AB  - This retrospective study was designed to investigate the relationship between
      overexpression of the 67 kD laminin receptor (67LR) using immunohistochemistry,
      and several clinicopathological parameters including overall survival in human
      gastric adenocarcinoma. We stained paraffin-embedded sections of 93 resected
      primary gastric adenocarcinomas using a polyclonal antibody specific for the 67LR
      as well as monoclonal antibodies for p53 protein, epidermal growth factor
      receptor, proliferating cell nuclear antigen, carcinoembryonic antigen and
      chromagranin. The results showed statistically significant correlations between
      overexpression of the 67LR and types of early or advanced gastric carcinoma (p <
      0.001), depth of invasion (p < 0.001), WHO histopathologic classification (p <
      0.001), stage (p = 0.001), expression of p53 protein (p = 0.019), expression of
      epidermal growth factor receptor (p < 0.001) and proliferating cell nuclear
      antigen labeling index (p = 0.002). A lower proportion of signet ring cells
      revealed a higher percentage of overexpression of 67LR in both early (p < 0.002)
      and advanced (p < 0.001) gastric carcinomas. Intestinal type adenocarcinoma
      (according to Lauren's classification) revealed a higher percentage of
      overexpression of the 67LR than the diffuse type in both early (p = 0.057) and
      advanced (p < 0.001) gastric carcinomas. The correlations between overexpression
      of the 67LR and lymph node metastasis were statistically significant (p < 0.07).
      Although the overexpression of the 67LR tended to correlate with lower survival
      rates, the correlation was not statistically significant due to the limited
      sample size. Our data revealed that overexpression of the 67LR is correlated with
      the progression of gastric carcinoma. The expression of the 67LR may be important
      as one of the steps which determines invasiveness during the progression of
      cancer.

PMID- 9182289
TI  - A flow cytometric study of early gastric cancer. The detection of high
      proliferative activity adds important information to the prognosis.
AB  - The prognostic value of DNA ploidy and proliferative activity has been rarely
      investigated in early gastric carcinoma (EGC). In the present study the ploidy
      pattern and cell cycle related parameters were evaluated in formalin-fixed
      paraffin-embedded specimens of 71 followed-up EGCs and compared with that of 20
      advanced gastric carcinomas (AGC) using flow cytometry. The results showed that
      ploidy pattern did not affect patient outcome. On the contrary, EGC with a high S
      phase had a worse prognosis. No significant differences in proliferative activity
      were detected between EGC and AGC. Fatal EGC had an S-phase higher than AGC. In
      conclusion, proliferative activity seems to affect the prognosis of EGC
      independent of the stage and could contribute to the identification of aggressive
      types of EGC.

PMID- 9182290
TI  - LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions.
      Prognostic implications.
AB  - The APC/MCC gene (Familial Adenomatous Polyposis) at 5q21 plays a role in colon
      cancer carcinogenesis. LOH at this locus has also been described in gastric
      cancer and preneoplastic lesions. The APC locus has been recently related to a
      cell surface adhesion molecule and its alteration may favour metastatic
      dissemination. LOH at 5q21 has been associated with poor prognosis in other
      tumors such as lung cancer. Thirty-six gastric cancers were evaluated for LOH at
      5q21 with 2 polymorphic markers from microdissected paraffin-embedded material.
      All tumors were classified by stage, histologic type, degree of differentiation
      and survival rates. In 4 cases, intestinal metaplasia cells in the adjacent
      mucosae were also microdissected. Six cases of moderate-severe gastric dysplasia
      were also added to the study. LOH was determined in 84% of the informative cases
      of GC, affecting both early and advanced stages of disease. Genomic instability
      was assessed in 5 cases, 3 of them associated with LOH. The only case of gastric
      cancer that did not show LOH or instability at 5q21 was a stage II, poorly
      differentiated intestinal carcinoma without evidence of recurrence after a 36
      month follow-up period (the mean survival rate in our series was 28.3% at 36
      months). We also found LOH in 2/6 dysplastic lesions and 1/4 intestinal
      metaplasias. Our data show that LOH at 5q21 is frequent in gastric cancer and is
      also present in intestinal metaplasia and dysplastic lesions. LOH at this locus
      is not a prognostic factor in GC in our study, due to the high incidence of LOH
      that we found.

PMID- 9182291
TI  - Mucoepidermoid carcinoma in a salivary duct cyst of the parotid gland.
      Contribution to the development of tumours in salivary gland cysts.
AB  - Concerning the hypothesis that distinct types of salivary gland cysts may be the
      starting point of a salivary gland tumour, a histological examination of 1,661
      salivary gland cysts was performed in order to analyse the cell types and their
      proliferative activity. Epithelial alterations were found especially in salivary
      duct cysts of parotid gland and in mucous retention cysts of minor salivary
      glands. Characteristic cellular changes were epithelial metaplasias (goblet
      cells, clear cells, squamous cells) and focal epithelial proliferations with
      plump or papillary plaques projecting into the cyst lumen. Only in one case had a
      mucoepidermoid carcinoma developed in the wall of a parotid duct cyst. The
      epithelial metaplasia and focal proliferative activity in salivary duct cysts is
      comparable to similar alterations in odontogenic cysts as possible early
      manifestation of a tumour, especially of an ameloblastoma or mucoepidermoid
      carcinoma. The differential diagnosis of salivary duct cysts must take primarily
      cystadenomas and cystic mucoepidermoid carcinomas of well-differentiated type
      into account.

PMID- 9182293
TI  - The standard isoform of CD44 is preferentially expressed in atypical papillomas
      and carcinomas of the choroid plexus.
AB  - Isoforms of the CD44 adhesion molecule have been assigned a pivotal role in tumor
      invasion and metastasis. CD44 splice variants may be selectively expressed in
      various normal and neoplastic tissues. We investigated immunohistochemically the
      presence of the standard (H) and two variant (v3, v6) isoforms of the CD44
      molecule in a series comprising 13 choroid plexus papillomas (WHO grade I) and 8
      carcinomas (WHO grade III). In the papilloma group, 5 tumors showed variable
      cellular pleomorphism and foci of infiltrative growth, and were tentatively
      classified as atypical papillomas. Autopsy specimens of normal pediatric and
      adult choroid plexus were used as control. Western-blot analysis of CD44H was
      carried out on 4 carcinomas, 1 papilloma and on normal choroid plexus. The
      proliferation rate was assessed by MIB-1 immunoreactivity. The normal choroid
      plexuses and 9 papillomas were negative for the standard as well as the variant
      CD44 molecules investigated. Four atypical papillomas and 5 carcinomas expressed
      CD44H. CD44v3 and CD44v6 were only detected in one of the atypical papillomas
      also positive for CD44H. These data indicate that CD44H is preferentially
      expressed on atypical papillomas and carcinomas and may correlate with the
      infiltrative growth of these tumors.

PMID- 9182292
TI  - Sarcomatoid transitional cell carcinoma of the renal pelvis. A report of five
      cases with clinical, pathological, immunohistochemical and DNA ploidy analysis.
AB  - Sarcomatoid transitional cell carcinoma of the renal pelvis is a rare neoplasm
      with only 7 well illustrated examples reported. These tumours can assume a
      partial or complete spindle cell pattern of growth, leading to the erroneous
      classification as sarcomas. We describe the clinic-pathologic features of five
      additional examples of sarcomatoid carcinoma of the renal pelvis observed in
      three males and two females. The age ranged from 65-to-82 years-old (mean 71.6).
      All these patients were treated by nephrectomy and died of disease between 6 and
      20 months (mean 11.2) after the onset of symptoms. An immunohistochemical study
      demonstrated coexpression of keratins, epithelial membrane antigen and vimentin.
      The image DNA ploidy of all the tumours showed an aneuploid pattern.

PMID- 9182294
TI  - Signet-ring carcinoma of the prostate.
AB  - A case of prostatic signet-ring adenocarcinoma is described in a man with a
      history of open prostatectomy for prostate carcinoma (18 years previously).
      Immunostaining confirmed the prostatic origin of the signet-ring tumor which
      stained for prostatic acid phosphatase (PSAP) and prostate specific antigen
      (PSA). Cytokeratin immunostaining showed the vacuoles to be true lamina with
      clear and distinct outlines, the feature confirmed by ultrastructural
      examination. This aggressive tumor is an uncommon but distinct variant of primary
      prostatic carcinoma which should be distinguished from artefactual vacuolation of
      tumor, inflammatory and stromal cells, and metastatic disease.

PMID- 9182295
TI  - p53 in a thyroid follicular carcinoma with foci of poorly differentiated and
      anaplastic carcinoma.
AB  - The clinical and pathologic features of a rare case of follicular carcinoma with
      small foci of poorly differentiated and anaplastic carcinoma are presented. Eight
      years after the removal of the primary neoplasm, the patient developed pulmonary
      and brain metastases that were predominantly composed of the poorly
      differentiated and anaplastic components. A comparative immunohistochemical and
      molecular analysis of p53 status in the follicular, poorly differentiated and
      anaplastic components of the tumor was performed. p53 immunostaining was
      restricted to the poorly differentiated and anaplastic areas. Single strand
      conformation polymorphism analysis (SSCP-PCR) from DNA obtained by
      microdissection demonstrated the presence of a mutation (TAT-->TGT; Tyr-->Cys) in
      codon 220, exon six of the p53 gene in the anaplastic component, that was absent
      in the well-differentiated follicular areas. The results of that study in this
      rare tumor support that p53 has a tumor progression role in thyroid
      tumorigenesis.

PMID- 9182296
TI  - Lipoblastic differentiation in a primary localized fibrous mesothelioma of the
      peritoneum.
AB  - Lipoblastic differentiation in fibrous mesotheliomas is an extremely rare
      occurrence. We present the histological and immunohistochemical features of a
      case of localized peritoneal mesothelioma with lipoblastic differentiation in an
      80-year old man and discuss the differential diagnosis with liposarcoma.

PMID- 9182297
TI  - Retroperitoneal liposarcoma in two siblings.
AB  - We report here on two cases of retroperitoneal liposarcoma which heterochronously
      occurred in two siblings. A huge myxoid liposarcoma, 20 x 14 cm size, was noticed
      in a 33-year-old female, who died with multiple liver metastasis in about half a
      year. Two years later after the death of the younger sister, pleomorphic
      liposarcoma, 8 x 8 cm in size, was noticed in a 39-year-old male who died with
      local recurrence and multiple metastasis one year after the operation. Their
      mother (69 years old) had had an operation for malignant fibrous histiocytoma of
      the right thigh at age 66. There was no evidence of multiple lipomatosis, an
      autosomal dominant trait, in the siblings or their family. Diverse soft-tissue
      sarcomas, but not liposarcoma, occur excessively in siblings with the syndrome of
      Li-Fraumeni. To our knowledge this is the first such report of its sibship
      occurrence.

PMID- 9182298
TI  - A case report of Down syndrome and centroblastic lymphoma.
AB  - We describe a case of left cervical stage I centroblastic lymphoma in a 29-year
      old male patient with Down's syndrome due to a (14; 21) Robertsonian
      translocation. The disease presented as extensive lymph node necrosis leaving
      rare areas of tumor cells, accounting for the diagnostic difficulties. According
      to our review of the literature, lymphoma is one of the most common neoplasms in
      DS patients and may represent the second most common malignancy in this
      condition, far behind leukemia.

PMID- 9182299
TI  - Simulation of right atrial cardiac myxoma by silent hepatocellular carcinoma.
AB  - A clinically silent hepatocellular carcinoma presenting as a mixoma of the right
      atrium is described. Intra-atrial growth has been reported in advanced,
      clinically manifested cases of liver carcinomas in African and Japanese subjects,
      but very occasionally in Caucasian people. Our case further suggests that this
      occurrence should also be considered in Western Countries.

PMID- 9182300
TI  - Chromophobe renal cell carcinoma. Pathologic, ultrastructural,
      immunohistochemical, cytofluorometric and cytogenetic findings.
AB  - A case of chromophobe renal cell carcinoma is reported in a 73 year-old man.
      Light microscopically, the tumor was composed of polygonal cells with a slightly
      eosinophilic and a fine reticular pattern, and a reaction of the cytoplasm with
      Hale's acid iron colloid. Ultrastructural analysis showed membranous
      microvesicles within the tumor cells, with degenerated mitochondria.
      Immunohistochemical profile against intermediate filaments was positive to
      cytokeratin 18 and negative against vimentin. Flow cytometry and cytogenetics
      revealed a predominant hypertriploid population. Few cases have been published
      with flow cytometry and cytogenetic findings. We report a new case.

PMID- 9182302
TI  - Adrenal cortical adenoma with extensive fat cell metaplasia.

PMID- 9182301
TI  - Multilocular thymic cysts associated with thymoma. A case report.
AB  - The association of multilocular thymic cysts (MTC) with thymoma is exceedingly
      rare, and the pathogenesis of this combination is controversial. We describe the
      case of a 42-year-old man with an anterior mediastinal mass found to contain MTC
      and thymoma. A multilocular cystic mass, measuring 13 x 6.5 x 2 cm, was found in
      the right lobe of the thymus, and contained a 4.7 x 2 cm thymoma in its center.
      Microscopic thymomas, lipomatously involuted remaining thymic tissue, and
      lymphoid follicles with germinal centers were found in the walls of MTC as well
      as in the left thymic lobe. Non-specific chronic inflammation was also present in
      the walls. In addition, microcysts, which were only found at the periphery of the
      thymoma and covered with epithelium, might have been formed secondarily by
      dilatation of the perivascular spaces and of Hassall's corpuscles. These findings
      suggest that a chronic inflammatory process was responsible for the early
      formation and enlargement of this patient's MTC, and that while the cavities of
      the MTC expanded to various degrees, the thymoma, which originated from one of
      the microscopic thymomas in the walls of MTC, increased in size, and grew to
      involve the remaining thymic tissue.

PMID- 9182303
TI  - Protection by taurine against adriamycin-induced proteinuria and hyperlipidemia
      in rats.
AB  - Taurine was used in the present study to evaluate its beneficial effects against
      proteinuria and hyperlipidemia associated with nephrotic syndrome. Rats made
      nephrotic with adriamycin had a high excretion of protein, albumin, and N-acetyl
      beta-D-glucosaminidase compared with nonnephrotic rats. Nephrotic rats manifested
      hyperlipidemia with significant elevation in all major lipoprotein fractions.
      Treatment with taurine significantly suppressed adriamycin-induced proteinuria,
      albuminuria, and urinary excretion of N-acetyl-beta-D-glucosaminidase. Treatment
      of rats wit taurine for 7 days before adriamycin, and daily thereafter,
      significantly lowered plasma cholesterol, triglycerides, phospholipids, lipid
      peroxides, and malondialdehyde associated with lipoprotein fractions. Similarly,
      total lipids, cholesterol, triglycerides, lipid peroxides, hydroperoxides, and
      hydroxyl radicals in the liver and kidneys of taurine-treated adriamycin rats
      were decreased significantly compared with adriamycin alone. Lecithin cholesterol
      acyl transferase activity and free fatty acid levels in plasma, lipoprotein
      lipase activity, glutathione, total thiol, and ascorbic acid in the liver and the
      kidneys of taurine-treated adriamycin groups were significantly elevated compared
      with adriamycin alone. These results suggest that taurine might be applicable as
      a protective agent for proteinuria and hyperlipidemia associated with nephrotic
      syndrome.

PMID- 9182304
TI  - [Simulation study of the influence of collimator defects on the uniformity of
      scintigraphic images].
AB  - The mechanical tolerances in building collimators for scintillation cameras are
      studied. A simulation method has been used to quantify the effects of defects in
      hole inclination and hole diameter on the uniformity of planar and tomographic
      images. The calculation takes into account the geometry of the hexagonal hole
      collimator, the camera intrinsic resolution, the object size, the pixel size, the
      effect of low-pass filtering, as well as the type, size and position of the
      defect. For instance, a 0.03 mm diameter defect on several holes located in the
      central region of a very high resolution collimator can result in a 12%
      uniformity artefact in tomographic imaging of an 18 cm diameter cylinder, using a
      3.45 mm resolution camera, 4.5 mm pixel size, and Hamming filtering with a
      Nyquist frequency cut-off. A 0.17 degree inclination defect of a few holes can
      result in the same uniformity artefact. These results show that the building of a
      collimator has to be very precise.

PMID- 9182305
TI  - Edible vaccines.
AB  - Vaccines were the result of trial and error research until molecular biology and
      genetic engineering made possible the creation of of many new and improved
      vaccines. New vaccines need to be inexpensive, easily administered, and capable
      of being stored and transported without refrigeration; without these
      characteristics, developing countries find it difficult to adopt vaccination as
      the central strategy for preventing their most devastating diseases. The authors
      describe a promising approach to inexpensive and effective vaccines: producing
      them in plants we commonly consume.

PMID- 9182306
TI  - The False Claims Act: litigating scientific misconduct II.

PMID- 9182307
TI  - [Transplantation today].
AB  - Purpose of this review is, to highlight key issues in transplantation medicine
      today and to summarise basic information on current state of perfused organ
      transplantation. There is special emphasis on ethical and legal considerations
      with regard to living donor transplantation, brain death concept, donor consent
      and organ allocation. Transplantation frequencies and the impact of whole organ
      transplantation on the treatment concept for patients with end stage organ
      disease is heavily dependent on donor and organ availability. Organ donor rate of
      25 to 30 donors per million inhabitants per year seems to yield sufficient organ
      supply for patients on renal replacement therapy. 15 to 20 liver transplantations
      per million inhabitants per year, my be sufficient, to cover the need of organs
      for non malignant end stage liver diseases. This frequency may be achieved by
      increasing donor rates and employing "split techniques", where one liver is used
      for two recipients. One year graft survival in kidney transplantation can be
      expected to be between 85 and 90%, one year patient survival in heart and liver
      transplantation can be expected to be beyond 80%. The risk of organ failure is
      highest in the first year, long term results are dependent on incidence of
      chronic rejection, comorbidity of the patient and original disease. Patient-
      and/or graft loss after the first year is in the order of 1 to 5%. Whole organ
      transplantation for kidneys, hearts and livers are considered routine procedures,
      lung transplantation is reaching standard phase, pancreas and combined pancreas
      kidney transplantation is well established technically, but its indication is
      still controversial.

PMID- 9182308
TI  - [Diagnostic imaging after liver transplantation].
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) has become an accepted
      treatment for end-stage liver disease. However, postoperative complications
      result in significant patient morbidity and mortality. Early detection and
      treatment of these complications is therefore of utmost importance. MATERIALS AND
      METHODS: We retrospectively reviewed the postoperative complications of the
      patients who underwent OLT at our institution. Duplex Doppler sonography and
      cholangiography were the primary imaging modalities in postoperative evaluation
      of the transplanted liver. Other important techniques were CT, MRI and
      angiography, which may contribute to a reliable diagnosis of vascular or biliary
      complications. RESULTS: Second to primary organ dysfunction, vascular
      complications are the most frequent cause of graft loss. Thrombosis of the
      hepatic artery is the most common and most serious vascular complication, with a
      reported incidence from 4 to 42%. Bile duct sludge, leaks and strictures are
      frequent complications after liver transplantation, which can contribute to graft
      dysfunction. Biliary tract complications usually occur within the first 3 months
      and require interventional radiological or surgical therapy. Since liver
      transplant recipients undergo immunosuppressive therapy, they are at increased
      risk of developing late post-transplant malignancies, which are best depicted by
      US, CT or MRI. However, radiological diagnosis of lympho-proliferative disorder
      has to be confirmed by liver biopsy. CONCLUSION: Cholangiography and Duplex
      sonography are routinely used in the postoperative evaluation of patients with
      OLT. CT, MRI, and angiography are problem-solving tools in equivocal cases.

PMID- 9182309
TI  - [Interventional radiologic procedures in postoperative complications after liver
      transplantation].
AB  - PURPOSE: Postoperative complications contribute significantly to the morbidity
      and mortality of liver transplant patients. The management of these complications
      requires a multidisciplinary approach in which interventional radiology plays an
      integral role. Indications, techniques, and results of radiological interventions
      in the management of the liver transplant patient are presented. MATERIAL AND
      METHODS: During a 10-year period, 52 out of 420 liver transplant recipients
      underwent radiological interventions, including angioplasty (n = 20),
      embolization (n = 2), percutaneous drainage (n = 11), and biliary interventions
      (n = 19). RESULTS: Nine out of ten arterial stenoses located at the anastomoses
      (n = 8), within the liver (n = 1) and in the coeliac trunk (n = 1) were
      successfully treated by balloon dilatation. Angioplasty of supra- or infrahepatic
      anastomotic stenoses of the i.c.v. (n = 5) provided long-term success only in
      combination with stent implantation. Portal vein stenoses and chronic thrombosis
      were treated by balloon dilatation and stent insertion via transhepatic
      catheterization of the portal vein. Late strictures of bile-duct anastomoses can
      be managed by ante- or retrograde interventions. If biliary complications are
      related to inflammatory or septic problems, the prognosis of graft survival is
      poor. CONCLUSION: Interventional radiological procedures are very useful in the
      management of vascular and biliary complications after liver transplantation.
      These techniques provide a cure in many situations, and thus, surgical
      interventions may be avoided in selected cases.

PMID- 9182310
TI  - [Diagnostic imaging within the scope of lung transplantation].
AB  - PURPOSE: Recent progress in both surgical techniques and therapeutic medication
      of immunosupression have made lung transplantation a promising option for
      patients with untreatable diseases of the lung parenchyma. Because preoperatively
      and postoperatively diagnostic imaging has crucial importance for patient
      management and clinical decision making we aim to describe imaging features of
      frequent pathologies in patients after lung transplantation. MATERIALS AND
      METHODS: We reviewed radiological examinations of patients after lung
      transplantation performed at our institution over a period of four years, and
      exemplary cases were selected for presentation. Our interest was focussed on both
      conventional and CT-imaging of postoperative alterations, infections, organ
      rejection, and pathologies of the airways. Moreover, post-biopsy alterations and
      lymphoproliferative disorders were documented. Together with clinical information
      we aimed to give a concise description of specific pathologic entities. Also, the
      diagnostic impact of more recent techniques such as spiral-CT and thin-section CT
      should be discussed. RESULTS: In cases of early postoperative pathologies and in
      infections conventional radiography is diagnostically reliable when interpreted
      together with clinical information. In cases of acute or chronic organ rejection,
      of lymphoproliferative disorders, of diseases of central or small airways, and
      for the choice of an appropriate biopsy site, CT has proved to be a valuable
      imaging modality. Spiral-CT allows airway volumetry in cases of strictures or
      dehiscence, thin-section CT enables assessment of subtle parenchymal pathologies,
      notably in cases of chronic organ rejection. DISCUSSION: The radiographic
      findings described below represent specific pathogenetic entities in lung
      transplant patients (postoperative alterations, infections, posttransplant
      lymphoproliferative disorders). Their accurate recognition will have a positive
      impact on the further clinical history. In the near future, more sophisticated CT
      techniques should widen our pathogenetic knowledge of alterations in transplanted
      lungs.

PMID- 9182311
TI  - [Radiologic interventions in anastomosis complications after lung
      transplantation].
AB  - PURPOSE: Bronchial and arterial anastomotic stenoses are major complications
      after lung transplantation. Interventional techniques provide a definitive cure
      in certain cases. MATERIAL AND METHODS: Three out of four patients had ischemia
      related stenoses of the bronchial anastomoses postoperatively; one patient
      developed malacia of the bronchus main stem 1 year after transplantation. Four
      patients has stenoses of the arterial anastomoses, which resulted in hemodynamic
      instability and reduced perfusion of the graft. RESULTS: Stent implantation in
      the bronchial anastomoses (n = 3) and in the main stem (n = 1) improved
      ventilation and oxygen saturation in all patients. The stents were incorporated
      by mucosal overgrowth, as demonstrated by endoscopy, as early as 6 weeks after
      implantation. Balloon dilatation (n = 3) and stent implantation (n = 1) were
      successfully performed in 4 patients with stenoses of the arterial anastomoses.
      The mean transstenotic pressure gradient of 9.5 mm Hg was reduced to 2.2 mm Hg
      after angioplasty. Lung perfusion shifted towards the grafts, as shown by 99mTc
      perfusion scans. CONCLUSION: The minimally invasive techniques of interventional
      radiology are very effective in the treatment of anastomotic complications after
      lung transplantation and may avoid surgery in certain cases.

PMID- 9182312
TI  - [Magnetic resonance tomography without and with gadolinium-DTPA for evaluating
      kidney transplants].
AB  - PURPOSE: To determine the value of MR imaging in differentiating the various
      causes of human renal allograft dysfunction. METHODS: A total of 123 human renal
      allografts (normal n = 20, acute rejection n = 57, acute tubular necrosis n = 14,
      interstitial fibrosis n = 11, chromic allograft glomerulopathy n = 11,
      cyclosporine nephrotoxicity n = 3, cortical necrosis n = 7) were investigated by
      means of MR imaging. Axial T1-weighted spin-echo images and coronal T1-weighted
      gradient-echo images were obtained before and after Gd-DTPA injection. Diagnostic
      parameters included corticomedullary contrast and allograft size and shape on the
      pre-contrast sequences. RESULTS: None of the diagnostic parameters used could
      differentiate among the various diagnostic groups. Diagnostic of cortical
      necrosis could be made only on post-contrast scans. Contrast-enhanced scans were
      superior to pre-contrast images in detection of focal allograft lesions.
      Otherwise, contrast-enhanced scans did not provide any more information than pre
      contrast studies. Spin-echo and gradient-echo sequences displayed the same
      diagnostic value. CONCLUSIONS: MR imaging has a limited value in differentiating
      the various causes of renal allograft dysfunction.

PMID- 9182313
TI  - [Functional MR urography in patients with kidney transplantation].
AB  - PURPOSE: To assess the value of functional magnetic resonance urology for the
      noninvasive postoperative evaluation of renal transplants. METHODS: A saturation
      inversion projection sequence allows the selective imaging of strongly T1
      weighted signal from the MR contrast agent. A control slab leads to images
      comparable to conventional urography which can be acquired as a sequence with
      four images per minute. RESULTS: 15 patients with urologic questionable findings
      after renal transplantation were studied. FMRU revealed in 6 patients normal
      findings, in 6 moderate dilatation of the renal pelvis without any urodynamic
      relevant obstruction. 3 pathologic findings, ureteral leak, ureteropelvic
      junction obstruction and ureteral stenosis were diagnosed and consequently
      surgically treated. The imaging quality in all studies was diagnostic and
      urologically relevant. CONCLUSION: FMRU can be used as a noninvasive technique
      for the assessment of renal transplant in cases with suspicion of complication in
      the excretory system.

PMID- 9182314
TI  - [Initial experiences with contrast enhanced MR angiography after kidney and
      pancreas transplantation].
AB  - PURPOSE: The assessment of vascular complications by DSA in patients who have
      undergone kidney and pancreas transplantation is an invasive investigation and
      has the risk of nephrotoxicity caused by the iodinated contrast agent. The aim of
      this study was to compare the diagnostic value of noninvasive gadolinium-
      enhanced MRA with intraoperative and DSA results. PATIENTS AND METHODS: Eleven
      MRA investigations were performed in eight patients after kidney and pancreas
      transplantation. A fast T1-weighted 3D-gradient-echo sequence with short TR and
      TE was used in a dynamic technique including the three consecutive data
      acquisitions after a Gd-DTPA (Magnevist) injection. MRA was compared with
      intraoperative findings in all patients and with DSA in three patients. RESULTS:
      In the distal abdominal aorta, the internal and external iliac arteries, the main
      transplanted arterial vessels, and the arteries after first branching, high
      signal intensity was found. Assessment of renal and pancreatic parenchyma
      perfusion was possible in all patients. Venous transplant vessels could be
      depicted in four patients. CONCLUSION: Our initial experience with the MRA
      sequence used shows that this technique may be promising in the assessment of
      larger arterial transplanted vessels and kidney/pancreas parenchyma perfusion.
      Improvement of the MRA technique is necessary for transplanted venous vessels.

PMID- 9182316
TI  - [Acute abdomen with left-sided lower abdominal pain. Acute mesenterial ischemia
      with infarct of the small intestine in mesenteric vein s thrombosis and hepatic
      vein thrombosis].

PMID- 9182315
TI  - [Morphologic MR imaging with T1-weighted sequences for radiotherapy goal volume
      definition of intracranial tumors. Comparison with FLASH-Turbo-FLASH and SE
      sequences].
AB  - INTRODUCTION: The goal of this study was to compare contrast-enhanced T1-weighted
      Flash and Turbo-Flash sequences with conventional spin-echo sequences as a basis
      for planning high-precision radiotherapy. METHODS: A total of 25 consecutive
      patients with different intracranial tumors and a disrupted blood-brain barrier
      were studied. T1-weighted Flash, Turbo-Flash and conventional spin-echo images
      were evaluated after controlled 30-s infusion of 0.1 mmol/kg body weight of Gd
      DTPA. The evaluation of the three sequences included the measurement of the
      spinal- and contrast-to-noise ratios, the visual inspection of the tumors and
      artifacts, and the measurement of tumor size. RESULTS: The signal- and contrast
      to-noise ratios were significantly (P < 0.05-0.01) lower for Flash and Turbo
      Flash than for conventional spin-echo sequences. However, visual inspection of
      the contrast-enhancing tumors revealed in 23 and 24 of 25 lesions on Flash and
      Turbo-Flash images, respectively, good or very good tumor visibility when
      compared with conventional spin-echo images with a reduction of imaging time by a
      factor of 7-8. Flash and Turbo-Flash sequences were more prone to susceptibility
      artifacts, conventional spin-echo sequences more to pulsation artifacts in the
      posterior fossa. Tumor sizes were comparable in all three techniques. CONCLUSION:
      At present, conventional spin-echo images are superior to fast Flash and
      ultrafast Turbo-Flash sequences as a basis for accurate target volume definition
      in high-precision radiotherapy. However, fast Flash and Turbo-Flash images may be
      a practicable alternative to conventional spin-echo images for tumors in the
      posterior fossa or in patients unable to tolerate a stereotactic fixation device.
      Despite some limitations, Turbo-Flash sequences enable fast dynamic MR imaging
      combined with an acceptable morphology, which may be sufficient to target volume
      planning in high-precision radiotherapy.

PMID- 9182317
TI  - [Pathologic liver findings? Hilar cholangiocarcinoma (Klatskin tumor) with
      central calcinosis].

PMID- 9182318
TI  - Proceedings from the 4th International Conference on Fertility Control for
      Wildlife Management. Great Keppel Island, Queensland, 8-11 July 1996.

PMID- 9182319
TI  - Acquiring language.

PMID- 9182320
TI  - Acquiring language.

PMID- 9182321
TI  - Acquiring language.

PMID- 9182323
TI  - A deadline for an AIDS vaccine.

PMID- 9182322
TI  - Acquiring language.

PMID- 9182324
TI  - Panel weighs a law against cloning.

PMID- 9182325
TI  - Hughes network expands by a big leap.

PMID- 9182326
TI  - Sequencers call for faster data release.

PMID- 9182327
TI  - Antisense aims for a renaissance.

PMID- 9182328
TI  - Nonlinear molecules trip the light.

PMID- 9182329
TI  - Looking for leads in HIV's battle with immune system.

PMID- 9182330
TI  - Planned tests in Thailand spark debate.

PMID- 9182331
TI  - Throttles and dampers: controlling the engine of membrane fusion.

PMID- 9182332
TI  - Sticky endings: separating telomeres.

PMID- 9182333
TI  - [Cystic nephroma].

PMID- 9182334
TI  - [Comparison of different contrast medium boluses in rapid dynamic CT studies].

PMID- 9182335
TI  - [Value of magnetic resonance tomography in diagnosis of drug-resistant epilepsy].

PMID- 9182336
TI  - [Diagnostic value of late CT images of liver metastases in comparison with spiral
      CT].

PMID- 9182337
TI  - [PML: progressive multifocal leukoencephalopathy].

PMID- 9182339
TI  - [Congenital diaphragmatic cyst in a child].
AB  - The case of 8-year-old boy with congenital diaphragmatic cyst is presented. The
      aspects of the origin of this anomalies, the surgical finding and the method of
      the reconstruction of diaphragma are described.

PMID- 9182338
TI  - [An artificial urinary bladder sphincter for men].
AB  - Urinary incontinence is a condition with involuntary escape of urine and causes
      not only medical but also social and hygienic problems. One of the causes of
      incontinence is insufficiency of the urethral closure mechanism which in men is
      usually caused by previous prostatectomy or neurogenic dysfunction of the lower
      urinary pathways. The method of choice is the application of an artificial
      sphincter (model AMS 800) to the bulbar urethra or cervix. The authors applied an
      artificial sphincter in 1993-1996 to one boy and 14 men aged 11-72 years. The
      basic components of the artificial sphincter of the urethra-AMS 800 is a cuff,
      balloon and pump. The whole system is filled with isotonic solution Omnipaque
      300, the cuff which is 45-80 mm long is placed either round the bulbar urethra
      from a perineal approach or round the cervix by a retropubic approach. The pump
      is placed beneath the skin of the scrotum and the balloon is in a perivesical
      position. All parts of the AMS are connected by tubes. Because of infectious
      complications the authors had to explant the sphincter in two patients. In one
      patient it was necessary to add another cuff. The perineal approach is simpler,
      but is associated with a higher risk of erosion of the urethra. Patients with a
      neurogenic bladder had more complications than those after prostatectomy. Despite
      the fact that the method and aid is expensive, the treatment is very effective
      and makes the patients independent on other aids for incontinent patients.

PMID- 9182340
TI  - [Initial experience with percutaneous endoscopic gastrostomy in a surgery
      department].
AB  - The authors present their initial experience with percutaneous endoscopic
      gastrostomy and draw attention to its advantages and risks. As a basis they use
      their own group of patients, most of them in a very poor condition where it
      proved possible to ensure by this method enteral nutrition on a long-term basis.

PMID- 9182341
TI  - [The importance of tapering the intestines in congenital intestinal atresia].
AB  - Extensive intestinal resections in inborn intestinal atresias are the second most
      frequent cause of the short gut syndrome. Because treatment of this condition is
      so far minimal, prevention is of fundamental importance. One possible approach is
      tapering of the gut, i.e. longitudinal antimesenterial resection of the gut. At
      the Clinic of Paediatric Surgery in 1991-1995 30 patients with inborn atresias of
      the gut were operated (17 atresias of the duodenum, 11 atresias of the small
      intestine, 2 atresias of the large intestine). Six patients (20%) died. In 2
      patients (one girl with atresia of the colon and one boy with atresia of the
      jejunum) developed dilatation of the gut orally from the site of resection of the
      atresia and a chronic subileous condition. Instead of resection of the dilated
      portion the gut was modelled by tapering. In both children the passage improved
      and the children thrive. Based on data in the literature and their own experience
      the authors assume that tapering of the gut should supplement primarily high
      jejunal atresia, apple peel syndrome and extensive dilatation of the jejunum.
      Tapering cannot be used above the aganglionic portion of the intestine.

PMID- 9182342
TI  - [Pitfalls in intravesical immunotherapy of superficial carcinoma of the
      gallbladder with BCG vaccine].
AB  - The authors present their experience with the use of BCG immunotherapy in the
      treatment of superficial carcinoma of the urinary bladder in 30 patients as
      regards side-effects and tolerance of preparations. In the discussion they deal
      in particular with the classification and therapy of side-effects.

PMID- 9182343
TI  - [Surgery of gastroduodenal ulcers in the Czech Republic].
AB  - OBJECTIVE: Evaluation of surgical treatment of gastroduodenal ulcers during the
      past 20 years and its importance at the present time. METHOD: During the past 20
      years three questionnaire surveys were implemented in surgical departments in the
      Czechoslovak Republic (1975-57 departments, 1989-80 departments) and in the Czech
      Republic (1994-80 departments) focused on surgery of gastroduodenal ulcers. The
      authors analysed also a group of patients from their own department covering a
      five-year period (1990-89 operations and 1995-27 operations). RESULTS: In
      surgical departments of the Czechoslovak and Czech Republic the ratios of
      different operations during the mentioned years were as follows: 1975: resections
      85%, vagotomy 9%, suture of perforation 6%. 1989: 71%, 10%, 19% and 1995: 48%,
      8%, 31% and other operations 13%. In the authors department the ratio of these
      operations in 1990 was as follows: 23%, 23%, 10% and in 1995: 59%, 7%, 23%, 11%.
      The surgical approach declined in the course of five years by 70%. During the
      last two years in the Czech Republic and in the authors department first
      experience was assembled with laparoscopic suture of perforated ulcers and with
      superselective vagotomy. The initial results are very encouraging. CONCLUSION:
      The basis of treatment of gastroduodenal ulcers is modern medicamentous
      treatment, surgery is indicated most frequently if conservative treatment fails
      or in case of haemorrhage (78% of haemorrhages are controlled endoscopically). In
      gastric ulcers resection is indicated most frequently, similarly as in
      complications of duodenal ulcers. In non-complicated duodenal ulcers
      superselective vagotomy is an equivalent alternative of long-term conservative
      treatment.

PMID- 9182344
TI  - [Bilateral nephrectomy--a life-saving procedure].
AB  - Authors report a rare case of complications that occurred after an invasive
      urodynamic examination. In order to save the life of a patient with a bilateral
      acute abscessing pyelonefritidis due to pseudomonad uroseption and accompanied by
      a shock status with multi-organ failure it was necessary to perform the complete
      bilateral nefrectomy. After removing of the infection zone, i.e. -both kidneys, 
      the status of the patient dramatically improved. The patient survived and is
      taking part in dialysis-transplantation programme.

PMID- 9182345
TI  - [Prenatal use of a vesico-amniotic shunt in obstructive uropathy].
AB  - Obstructive uropathy was diagnosed in a fetus in the 31st week of gestation. Good
      renal functioning and a low L/S index (lecithin/sphingomyelin) in amniotic fluid
      having been found, a vesocoamniotic shunt was inserted percutaneously. Draining
      through the shunt lasted for three weeks; then the gravidity was terminated due
      to stent dislocation while the lung maturity was good. After delivery, right
      kidney afunction, 4th-5th degree reflux and left-sided hydroureter were
      diagnosed. At the age of one year, nephrectomy on the right, left-sided
      hydroureter resection and plastic correction of the megaloureter on the right
      were performed. The child's condition is satisfactory.

PMID- 9182346
TI  - [Histologic findings in kidney tumors].
AB  - The authors present a group of 304 adult patients (with the exception of one
      child with a Wilms tumour) from 1988-95 with the diagnosis of a primary renal
      tumour treated by surgery and subsequently subjected to histological examination.
      The tumours were in 83.9% clear renal cell tumours (Grawitz carcinoma), 4.3% were
      papillary carcinomas, 3.3% renal cortical adenomas, 3.9% oncocytomas and 2.0% non
      differentiated carcinomas, 0.7% angiomyolipomas, 0.7% chromophobe cell renal
      carcinomas, 0.7% secondaries (carcinoma of the breast and testis), 0.7%
      multilocular cysts, one case each (0.3%) Wilms tumour, malignant lymphoma,
      necrotic histologically not classifiable tumour. The authors give a more detailed
      account of multilocular cystic RCC (which accounts for 5.9% Grawitz tumours),
      papillary tumours, chromophobe cell renal carcinoma, oncoytoma and
      angiomyolipoma. The authors correlate briefly the histological findings with
      preoperative graphic examinations. They are very sceptical as regards assessment
      of the histological type of tumour from preoperative graphic examination (with
      the exception of angiomyolipoma). Finally the authors suggest classification of
      renal expansions from the urologists aspect-in the first place from preoperative
      graphic examinations for non-neoplastic lesions (in particular cysts and
      hypertrophy of the columna Bertini), parenchymatous tumours and tumours of the
      renal pelvis and secondly (mainly in parenchymatous tumours) histological
      classification is taken into account.

PMID- 9182347
TI  - Ocular effects of prostaglandins and other eicosanoids. Symposium proceedings.
      Fort Lauderdale, Florida, USA, May 12-13, 1995.

PMID- 9182348
TI  - [Regulation of working hours sold for money?].

PMID- 9182349
TI  - [To be discharged?].

PMID- 9182350
TI  - [Implantable pacemaker-cardioverter-defibrillator. A cost-effective and life
      prolonging treatment].

PMID- 9182351
TI  - [Spinal anesthesia in ambulatory surgery?].

PMID- 9182352
TI  - [Spinal anesthesia in ambulatory surgery. Extent, routines and patient
      satisfaction].
AB  - Spinal anaesthesia has been used in day-care surgery for a long time, but the
      fear of past dural puncture headache has limited its use in younger patients. A
      survey was conducted in order to assess the extent to which spinal anaesthesia is
      used for day-care surgery, and the routines governing the present practice in
      Norwegian anaesthetic departments. Information was obtained on the use of spinal
      anaesthesia for day-care surgery. In half of the anaesthetic departments spinal
      anaesthesia was used regularly. A large proportion of the departments worked with
      a lower age limit over 30 years of age for use of spinal anaesthesia. This does
      not seem to be justified on the basis of the scientific evidence. A prospective
      patient study revealed that out of 120 day-care patients aged 15 to 45 years who
      were given spinal anaesthesia, 93% would accept the same kind of anaesthetic
      again. Based on recent studies, the fear of post dural puncture headache should
      not preclude the use of spinal anaesthesia as a good alternative to general
      anaesthesia in day-care surgery.

PMID- 9182353
TI  - [Pulmonary changes as primary manifestations in Waldenstrom macroglobulinemia].
AB  - We describe a patient with a 19-year history of lymphocytic lung infiltrations. A
      diagnosis of lymphocytic interstitial pneumonitis was made in 1982 after an open
      lung biopsy, but in 1995 a comprehensive re-evaluation led to the diagnosis of
      Waldenstrom's macroglobulinaemia with primary bronchopulmonary involvement. It
      could also be demonstrated by polymerase chain reaction and immunological
      techniques that this disease had been present since before 1982. In 1995 it was
      still difficult to demonstrate bone marrow involvement, even with new and
      sensitive methods. We discuss some diagnostic problems of organ manifestations of
      uncommon systemic diseases. Pulmonary manifestations of Waldenstrom's
      macroglobulinaemia or other diseases of the immune system should be considered in
      patients with atypical lung disorders.

PMID- 9182354
TI  - [Hepatic vein thrombosis. Diagnostic and therapeutic difficulties].
AB  - Budd Chiari syndrome (liver vein thrombosis) may be a diagnostic and therapeutic
      problem. On the basis of four different cases we review the major diagnostic and
      therapeutic principles involved. Imaging techniques are necessary in order to
      establish the diagnosis. Ultrasound examination with Duplex doppler is usually
      sufficient, but MR angiography is also useful. Treatment options are
      thrombolysis, surgery or liver transplantation. What treatment is selected will
      depend on the clinical situation and the prognosis.

PMID- 9182355
TI  - [Recurrent spontaneous abortions].
AB  - The publications on recurrent abortion are abundant and confusing. Not
      surprisingly, the reason is insufficient knowledge about the physiology of normal
      pregnancy. It is an almost impossible task to investigate abnormality in
      pregnancy when the normal conditions are unknown. In addition, most of the
      reports on miscarriages are based on unsatisfactory scientific methods. We have
      carried out a critical review of the literature. We discuss the aetiology of the
      condition, and describe the practice in our department for investigating and
      treating women who experience recurrent abortion.

PMID- 9182356
TI  - [Occurrence of bacterial vaginosis among abortion seekers].
AB  - Bacterial vaginosis is the most common vaginal infection during the fertile
      period. The clinical diagnosis is based on three of Amsel's four criteria: thin,
      grey-white discharge, vaginal fluid pH above 4.5, a fishy odour on addition of
      10% potassium hydroxide solution to the vaginal fluid, and the presence of clue
      cells on a saline wet mount. A probably more sensitive indicator of the diagnosis
      is based on Gram-stain, where the normal lactobacillus-dominated vaginal flora is
      changed to the lactobacillus deficient flora of bacterial vaginosis. The
      condition is probably associated with higher risk of complications in connection
      with pregnancy and gynaecological surgery. A prospective study of bacterial
      vaginosis based on microscopy of Gram-stained smears was conducted among 168
      women applying for first trimester abortion. The prevalence of bacterial
      vaginosis was 24% and of Chlamydia trachomatis 8.4%. Four patients (10.3%) in the
      vaginosis group were treated with antibiotics for certain or suspected
      postabortal endometritis, as against six patients (5.4%) in the group without
      bacterial vaginosis.

PMID- 9182357
TI  - [When physicians become ill. Difficult choices].
AB  - 39 Norwegian physicians have been interviewed and another 49 have either written
      down or dictated the history of their illness. In this article we focus on the
      doctors' dilemmas during the various stages of their illness. The general trend
      is to postpone seeking help, and to try to deny or hide, from themselves and
      others, the fact that they are seriously ill. The reasons for this are discussed.
      Some have difficulty in abandoning the role of doctor for that of patient; while
      others, who would prefer to be just a patient, are often not allowed this. Often,
      the doctor's doctor also experiences a conflict of roles. These dilemmas can tell
      us something of general interest about the role of the patient, the role of the
      doctor, and the patient/doctor relationship in society.

PMID- 9182358
TI  - [Disability pension after a factory close-down--eight years after].
AB  - A follow-up study of 97 persons who were granted a disability pension in 1987 or
      1988 after closure of a shipyard showed 82 alive in 1995. The predominant
      diagnoses were musculoskeletal complaints, heart disease and psychiatric
      disorders. The 82 who were still alive were in good health and satisfied with
      their pension. However, if the factory had not been closed down, many of them
      could probably have continued in work. For many of them, and especially the
      youngest, the first year on disability pension was difficult. Based on today's
      more restricted rules, we have estimated that 25% of the applications for
      disablement benefit would have been refused.

PMID- 9182359
TI  - [Doppler ultrasound of blood flow in the hepatic veins].
AB  - The blood flow in the hepatic veins can normally be studied easily by Doppler
      ultrasound. The pattern of blood flow in normal individuals is described, and its
      relation to the cardiac cycle and changing pressure in the right atrium. The
      blood flow shows variations in healthy persons, and may change in cases of heart
      disease and hepatic disease. Conditions such as atrial fibrillation, tricuspid
      regurgitation, abnormal relaxation, restrictive cardiomyopathy, constrictive
      pericarditis and cardiac tamponade are reflected in the hepatic veins, and the
      pattern of blood flow may help in diagnosis, and in grading the pathology. In
      cirrhosis and portal hypertension the heart-synchronous variation in velocity is
      reduced. This is due to increased resistance to blood flow across the liver and
      the pressure gradient becoming larger than the variations in pressure in the
      right atrium.

PMID- 9182360
TI  - [Symphysiotomy. A thought-provoking example of appropriate technique in the Third
      World].
AB  - Cutting through the symphysis pubis cartilage as a means of widening the birth
      canal during long, drawn-out deliveries was probably common in Europe at the turn
      of the century and presumably occurred even later. As a result of progress in
      hygiene and clinical practice, Caesarean section has become much more common in
      such situations. In developing countries, where supervision of pregnant women is
      non-existent or extremely poor, Caesarean section can be a dangerous operation.
      Mortality figures around 1-3% are common, and the women are left with the
      unfavourable prognosis of a uterine scar. Therefore, symphysiotomy is still
      practised in settings where neither hygiene nor material resources permit.
      Caesarean section, because it is simple to perform and makes a negligible demand
      on resources.

PMID- 9182361
TI  - [Current management of uncomplicated acute cystitis in general practice].
AB  - Uncomplicated acute cystitis, defined as acute lower urinary tract infection in
      an otherwise healthy, non-pregnant, adult woman, is the most frequent form of
      urinary tract infection managed in general practice. The current views on
      diagnosis and treatment are reviewed. Using clinical epidemiological concepts we
      focus on the importance of the medical history, but urinalysis can be regarded as
      an aid in the process of differential diagnosis. Most patients will be cured by a
      three-day oral course of antibiotic treatment. Longer duration of treatment gives
      no increase in the rate of cure, and a higher rate of side-effects. Several
      antibiotics may be used, and from an ecological point of view we encourage a
      varied prescription policy. No follow-up is needed unless the symptoms persist or
      reappear soon after treatment.

PMID- 9182362
TI  - [Ambulatory surgery and patients' experiences].
AB  - 76 patients were interviewed by telephone 7-10 days after ambulant surgery for
      varicose veins, hernia inguinalis or sterilization (women). Of those who received
      spinal anaesthesia 24% developed headache and another 8% back-pain. Half of those
      who received general anaesthesia were too sleepy to recall the information they
      were given when they left the hospital. 22% of the patients reported that if they
      had to undergo the same operation again they would prefer to be admitted to
      hospital as inpatients. The interviews revealed many "minor" problems that could
      have been solved by a phone call on the first day after operation.

PMID- 9182363
TI  - [Norwegian Society of Gynecology and Obstetrics--guidelines in obstetrics.
      Structure, process, results and evaluation].
AB  - This paper describes structure, process, results, and evaluation of the Norwegian
      Society of Gynaecology and Obstetrics' Guidelines in obstetrics. This work, which
      lasted for 2 1/2 years, involved almost all obstetrical departments in Norway and
      1/4 of all members of the Norwegian Society of Gynaecology and Obstetrics. All
      members of the Norwegian Society of Gynaecology and Obstetrics were invited to
      answer 24 questions. Of the 63% who replied to the questionnaire, 44% and 48%
      respectively stated that the Guidelines in obstetrics were very good or good. The
      introduction of the Guidelines in obstetrics led to changes in routines in more
      than 70% of the hospitals, and the different categories of hospital physicians
      changed their routines as well (55-65%). 83% of the heads of the departments
      stated that the Guidelines in obstetrics served partly or totally as the model
      for the obstetrical management guidelines. The evaluation and the experience of
      this quality assessment handbook serve as perspectives for future work.

PMID- 9182364
TI  - [Combination of several psychotherapeutic methods including
      psychopharmaceuticals. A case of obsessive-compulsive disorder].
AB  - The author describes the treatment of a patient with obsessive compulsive
      disorder and depression. The case shows that it may be fruitful to combine two
      different methods of psychotherapy with psychotropic medication. It is pointed
      out that in normal clinical psychiatric practice it may be better to use a
      combination of treatments rather than only one specific form of psychotherapy.

PMID- 9182365
TI  - [Expectations from a system of personal general practitioners. A questionnaire
      study among general practitioners in the municipality of Bergen].
AB  - Four municipalities in Norway have tested out a system of personal general
      practitioners, where all inhabitants aged 12 or more could choose their personal
      doctor. The doctor's responsibility, work-load and economy were determined by
      his/her specified list of patients. Doctors employed in primary health care
      showed a significant interest in the subject, and the ongoing personal doctor
      trial. To prepare for possible reorganization to this new system in the
      municipality of Bergen, a survey was carried out in January 1995 among all 145
      general practitioners in Bergen, of whom 70% responded. Data from the survey
      indicated that a larger share of women than men had low expectations concerning a
      system of personal general practitioners. Only 19 out of 101 general
      practitioners were positive to introducing such a system.

PMID- 9182366
TI  - [Physicians and social security].

PMID- 9182367
TI  - [Physicians and security--synergism or polarity?].

PMID- 9182368
TI  - [Calcium antagonists and safety].

PMID- 9182369
TI  - [Drug therapy of hyperlipidemia--unanswered questions].

PMID- 9182370
TI  - [Illegal sale of new antidepressive agents].

PMID- 9182372
TI  - [Palliative medicine].

PMID- 9182371
TI  - [Thought about an "expensive treatment"].

PMID- 9182373
TI  - [Waiting list guarantee and denial of this guarantee].

PMID- 9182374
TI  - [I give my patients a suicide weapon].

PMID- 9182375
TI  - [The role of pharmacists in hospitals].

PMID- 9182376
TI  - [Untenable conditions for research scientists at the medical faculty in Oslo].

PMID- 9182377
TI  - [Prostatic cancer].

PMID- 9182378
TI  - [Treatment of obesity of physiological basis].

PMID- 9182379
TI  - [Molecular biology and cardiology. Molecular mechanisms in heart failure].

PMID- 9182380
TI  - [Exposure to endotoxins in the environment. Occurrence and health hazards].
AB  - Endotoxins are lipopolysaccharides from the outer cell wall of Gram-negative
      bacteria. Exposure to endotoxins can take place in industries where organic
      material is handled, in agriculture, in garbage handling, and sewage treatment.
      Byssinosis defined as Monday chest tightness and slight dyspnoea in the work
      place has been related to endotoxin exposure in cotton mills, but studies
      indicate that similar symptoms may be found in other work places. Other symptoms
      are: Headache, nausea, gastrointestinal symptoms and influenza-like symptoms.
      Several studies have shown a decrease in FEV1 following exposure to endotoxins.
      The relationship between exposure to organic dust, microorganisms, endotoxins and
      other chemicals in the work place and disease needs further research.

PMID- 9182381
TI  - [Prostatic cancer: an expensive dilemma].
AB  - The aim of this retrospective study is to describe the increasing human suffering
      as well as the Health-Service costs in Denmark due to palliative treatment of
      prostate cancer, at a time characterized by a still more aggressive therapeutic
      approach to prostate cancer but without effective prognostic factors. All 719
      prostate cancer patients with residence in Aarhus County diagnosed over a five
      year period (01.01.79-31.12.83) identified by the Danish Cancer Registry were
      registered. The data originates from hospital case records and Death
      Certificates. The national incidence of prostate cancer has increased
      dramatically even without screening programs. These patients have a considerable
      need for hospital care and palliative treatment of their cancer disease from the
      time of diagnosis until death. Based on these data the Danish hospital expenses
      in 1995 due to palliative treatment of prostate cancer were calculated to amount
      0.72% of the total National Health Budget.

PMID- 9182382
TI  - [Prostate-specific antigen, acid phosphatases and rectal exploration in the
      diagnosis of prostatic cancer].
AB  - Eleven hundred and seven patients referred for urological evaluation including
      measurement of serumprostate specific antigen (PSA) measurement are reviewed.
      Prostate cancer was diagnosed in 105 patients. PSA was found to be superior to
      prostatic acid phosphatase in the discrimination between prostate cancer and
      benign prostatic conditions. In 105 patients with newly diagnosed prostate
      cancer, scintigraphic evidence of osseous metastases was found in thirty-seven.
      No patients with a serum PSA value less than three times the upper normal limit
      of the assay had a positive bone scan. Isotope bone scan can be omitted in these
      patients, if they are not considered candidates for curative treatment.

PMID- 9182383
TI  - [Prostatic cancer men under age 65. Occurrence and need for study].
AB  - Based on information from the nationwide Danish Cancer Registry, the development
      in prostate cancer incidence among Danish men under 65 years is reviewed. Changes
      in incidence rate, clinical stage and the number of possible candidates for
      radical treatment are discussed.

PMID- 9182384
TI  - [Physician time and the direct contact with patients at Roskilde County Hospital
      Fjorden].
AB  - Over a two week period (1994) the 27 physicians at Fjorden registered the time
      they used on direct and indirect treatment of in- and out-patients,
      administration, further training, supervision and research. Standardized criteria
      for the time spent on patient treatment were set up. Thirty-two percent of the
      total work time was used for direct treatment and a further 32% for indirect
      treatment (conferences, etc.) while the rest was used for other purposes. In
      relation to standardized 60 minutes or more treatment sessions, the survey
      revealed an average of 32-60% insufficient time spent on each patient per
      session. Fifty percent more physician time for direct treatment would be
      necessary to reach the standardized criteria for the total number of patients. We
      conclude that using 2/3 of the total work time available on treatment is
      acceptable. The great discrepancy between real and ideal use of physician time
      makes it important to further examine how to acknowledge dialogue as a
      psychiatric tool.

PMID- 9182385
TI  - [Physician time spent on indirect treatment and administration at Roskilde county
      hospital Fjorden].
AB  - Over a two week period (1994) the 27 physicians at a psychiatric hospital
      registered the time used on indirect treatment (conferences, rounds, etc.). This
      amounted to 21-37% of total time, while time spent on administration amounted to
      7-46% of total time depending on the seniority of the doctor involved. An
      estimated one hour per week per patient was used for indirect treatment. An
      insignificant amount of time was spent on interviews with relatives. We conclude
      that although it would be desirable to reduce the time spent on indirect
      treatment, the new demands made on community psychiatry with involvement of
      relatives, etc., would rather tend to give rise to more obligations in this area.

PMID- 9182386
TI  - [Physician time spent on training, supervision and research at the Roskilde
      county hospital Fjorden].
AB  - Postgraduate training for young doctors is an obligation for clinical
      departments. However there is a general impression that it has been difficult to
      acknowledge training as an activity in importance to patient treatment, and thus
      to give it the necessary priority. For a period of two weeks in 1994, all
      activities performed by doctors at a psychiatric hospital during working hours
      were registered. Special attention was given to activities concerning training
      and educational issues. These consisted of element such as theoretical courses,
      tutoring in daily clinical work and supervision of psychotherapy giving sessions.
      Furthermore it was registered whether the doctor had been receiving or giving the
      training. Junior registrars, senior registrars and consultants used 15, 13 and 5%
      of their time on training activities, however, during the period concerned the
      activities mainly consisted of attending external courses. Tutoring in the daily
      clinical work was non-existent. It is proposed that clinical positions that have
      training as a described part of their function should be secured.

PMID- 9182387
TI  - [Budesonide and beclamethasone dipropionate inhalation powders. The effect on
      bone and collagen turnover in children].
AB  - The objective of the study was to assess bone and collagen turnover in asthmatic
      children treated with dry powder budesonide from the Turbohaler and dry powder
      beclomethasone dipropionate from the Diskhaler in a dose of 800 micrograms/day.
      Thirteen prepubertal children with asthma were studied. The study was conducted
      as an open crossover study with two treatment periods and treatment free run-in
      and wash-out periods. All periods were of two weeks' duration. At day 14 in each
      period blood samples were taken for assessment of serum osteocalcin, the
      carboxyterminal propeptide of type I collagen (PICP), and the aminoterminal
      propeptide of type III collagen (PIIINP). At the same time urine was collected
      for assessment of creatinine corrected pyridinoline (uPYR/cr) and
      deoxypyridinoline (udPYR/cr) crosslinks. RESULTS: Osteocalcin concentrations were
      not influenced by any of the treatments. During budesonide treatment PICP was
      reduced by 18% (p = 0.03), PIIINP by 24% (p = 0.0002), uPYR/cr by 16% (p = 0.03)
      and udPYR/cr by 21% (p = 0.12). During treatment with beclomethasone dipropionate
      PICP was reduced by 20% (p = 0.01), PIIINP by 36% (p = 0.0002), uPYR/cr by 18% (p
      = 0.004) and udPYR/cr by 13% (p = 0.02). The suppressive effect of beclomethasone
      dipropionate on PIIINP was more marked than that of budesonide (p = 0.001). It is
      concluded that treatment with dry powder budesonide and beclomethasone
      dipropionate 800 micrograms/day is associated with suppression of bone and
      collagen turnover. The suppression seems to be more marked during treatment with
      beclomethasone dipropionate. Long term effects and effects of lower doses of
      budesonide and beclomethasone dipropionate on bone and collagen markers needs
      further study.

PMID- 9182388
TI  - [Segmental "portal hypertension". A rare cause of severe tractable variceal
      bleeding].
AB  - We present a 33 year-old man with massive upper gastrointestinal bleeding caused
      by a rare form of segmental portal hypertension. The patient developed a
      pancreatic abscess, which caused an isolated thrombosis in the splenic vein and
      the development of pronounced collaterals and bleeding fundus varices. The
      patient underwent splenectomy and recovered quickly hereafter. The literature is
      sparse on severe bleeding complications due to acute pancreatitis. The present
      case emphasizes the importance of recognition of unusual manifestations of common
      clinical conditions.

PMID- 9182389
TI  - ["The psychiatric law and schizophrenia"].

PMID- 9182390
TI  - [Apoplexy unit--not a must?].

PMID- 9182391
TI  - [How to examine your breast].

PMID- 9182392
TI  - [Uptake of amino acids in the rumen epithelium in sheep].
AB  - By the modification of the methods which are used for determination of amino acid
      uptake in the mammary gland and in the small intestine the uptake of 14C-lysine
      was measured in two parts of the sheep rumen epithelium in vitro. Three various
      lysine concentrations were used (0.95; 4.95 and 9.95 mM/l). Duration of the
      incubation was 15, 30 or 60 minutes. Comparison of the lysine distribution ratios
      as depending upon the duration of incubation period in the dorsal rumen sac at
      9.95 mM/l concentration revealed significant differences between at the 15 min
      and 60 min incubation (0.952 +/- 0.089 vs 1.931 +/- 0.108; P < 0.05,
      respectively) and between 30 min and 60 min incubation (1.165 +/- 0.138 vs 1.931
      +/- 0.108, P < 0.05, respectively)-Fig. 1. Comparison of the lysine distribution
      ratios as depending upon the duration of incubation period in the ventral rumen
      sac at 4.95 mM/l concentration revealed significant differences between the
      incubations of 15 and 30 min (1.182 +/- 0.131 vs 1.742 +/- 0.113; P < 0.05,
      respectively) and between the incubations of 15 and 60 min (1.182 +/- 0.131 vs
      2.10 +/- 0.204; P < 0.05, respectively)-Fig. 2. Comparison of the lysine
      distribution ratios in both the dorsal and ventral sac as depending upon the
      duration of incubation period after 15 min incubation revealed a significant
      difference at the 4.95 mM/l concentration 1.619 +/- 0.078 vs 1.182 +/- 0.131; P <
      0.05, respectively)-Fig. 3. Our results showed that the lysine uptake in the
      dorsal and ventral sheep rumen epithelium is dependent on the incubation duration
      only under certain concentrations of lysine. Differences in absorption of lysine
      between dorsal and ventral rumen epithelium are not mostly significant.

PMID- 9182393
TI  - [Control of gastrointestinal helminthiasis in pasture-reared lambs].
AB  - Two sheep herds kept in different geographic conditions with spring lambing by
      the end of March and April (herd No. 1: 400 ewes, 600 metres above sea level;
      herd No. 2: 450 ewes, 300 metres above sea level) were examined. The dynamics of
      gastrointestinal nematode and Moniezia spp. cestode egg counts in samples taken
      regularly every 4 to 5 weeks was studied during the year 1995 with the intention
      to verify the system of effective control of these helminth infections under
      pasture conditions of lamb rearing. In ewes a significant rise in
      gastrointestinal nematode egg counts was proved during the lambing season,
      "spring rise phenomenon", and during the summer pasture until autumn months with
      maximum EPG values reaching 150 (Figs. 1 and 2). In lambs that started grazing at
      1 to 4 weeks of age, the excretion steeply rose to maximum EPG values 350 and
      290, respectively, after 4 to 5 weeks of grazing (Figs. 1 and 2). In order to
      control these rising infections, ewes were treated with antihelmintic albendazol
      by the end of February (herd No. 1) and in March (herd No. 2) and lambs during
      the first or third decade of July. This anthelmintic treatment significantly
      lowered egg excretion to EPG values lower than 30 in ewes and 50 or 60,
      respectively, in lambs. Later, during the summer and autumn months, a mild rise
      of egg counts was found in lambs. These maxima were liquidated anthelmintis
      treatment in both herds in late autumn months and it also lowered helminth
      infections to minimum during winter months (EPG values lower than 50). The
      excretion of Moniezia spp. eggs had the same dynamics as that gastrointestinal
      nematodes. Values of lamb infection prevalence reached 21% in herd No. 1 and 29%
      in herd No. 2. Anthelmintic treatment during July controlled cestode findings in
      lambs. Albendazol (Vermitan susp. 2.5%), dosed 5 mg/kg of body weight, proved
      highly effective in the control of gastrointestinal nematodes and Moniezia spp.
      cestodes.

PMID- 9182394
TI  - [Validation of TKT medium for detection of Streptococcus agalactiae in bulk milk
      samples].
AB  - A selective medium for quantitative determination of Streptococcus agalactiae in
      bulk milk samples was tested. Among the medium bases, Edwards medium (EW)
      supplemented with 6 to 9% (v/v) of carefully washed sheep erythrocytes was proved
      to be best (Tab. V). The production of sphingomyelinasis C (BHE, Tab. II) or D
      (COREX, Tab. I) as a supplement supporting the formation of specific hemolytic
      zones in the medium, was tested in four strains of Staphylococcus aureus and
      seven strains of Corynebacterium pseudotuberculosis. Submersion aerated
      cultivation was used for enzyme production; optimum cultivation time is about 100
      hours (Figs. 1, 2). To determine the activity of the enzymes produced a screening
      method was developed applying hemolytic interactions with CAMP factor of Str.
      agalactiae. Method sensitivity and reproducibility are sufficiently high for the
      purposes of observation (Tab. III). The produced enzymes did not show any changes
      in their activity over the whole period of storage under all conditions of
      storage (32 days/7 degrees C, 48 weeks/-18 degrees C, lyophilizate 48 weeks/20
      degrees C). Sphingomyelinasis C is more resistant to heat denaturation, not
      losing its activity even after being warmed to 85 degrees C for 5 min;
      sphingomyelinasis D is sensitive to temperatures higher than 50 degrees C (Fig.
      3). COREX was selected (sphingomyelinasis D), produced by the strain CNTCC 18/62
      of C. pseudotuberculosis. The enzyme was applied either in raw filtrate of the
      medium (sterilization by repeated membrane filtration) or in prepurified form
      obtained by cold acetone precipitation, providing the same results. The medium is
      highly specific and likely enough selective for Str. agalactiae, unlike BHE it
      does not provide any positive results with UBERIS-factor+strains of Str. uberis
      (Tab. V). Optimum cultivation time is 18 hours; prolongation of cultivation for
      more than 24 hours brings about the risk of falsely positive readings (Tab. VI)
      in the strains of accompanying microflora (Morganella morganii ssp. morganii,
      delta-hemolytic staphylococci).

PMID- 9182395
TI  - [Changes in the microbial picture during the production of poultry salami].
AB  - Changes in microbiological parameters during the production of fine poultry
      salami was monitored in a private poultry-processing plant in Kosice within a
      period of six months. This product consists of meat paste or mechanically deboned
      poultry meat (MDPM), which is produced with the help of a Protecon MPB 30 E
      deboning machine, pork trimmings, water (in the form of crushed ice), salt,
      spices, and garlic paste. The main raw food material (hand-boned meat and skin
      from poultry carcasses intended for mechanical deboning), MDPM immediately after
      production, salted MDPM after its 24-hour-storage and ripening in the chiller,
      pork trimmings added to MDPM at an amount of 25%, prepared salami emulsion, and
      the final product (fine poultry salami) were examined for the presence of
      pathogenic and potentially pathogenic microorganisms. The total plate count, the
      counts of indicatory microorganisms (Coliforms and Enterococci), Staphylococci,
      psychrotrophic, proteolytic and lipolytic bacteria were also determined according
      to the Slovak government regulations. The results of the quantitative
      microbiological examination are shown in Figs. 1 and 2. It follows from them that
      the microbial load of poultry skin is considerably higher than that of hand-boned
      meat. During the deboning process an increase in all microbial parameters (on
      average by 1-3 radices) was noticed as compared with the raw food material
      (defrosted poultry carcasses before the mechanical deboning). MDPM contained
      10(4)-10(7) CFU/g; the count of coliforms ranged between 10(3) and 10(6)/g; the
      count of proteolytic and lipolytic bacteria between 10(4) and 10(6)/g; the count
      of Staphylococci and Enterococci between 10(2) and 10(4)/g. Staphylococcus aureus
      was discovered in about 50% samples of MDPM in an average concentration of
      10(2)/g. In addition to the groups of bacteria listed above, a wide range of
      potentially pathogenic microorganisms belonging to the family Enterobacteriaceae,
      especially those of the genus Proteus, Escherichia coli, Citrobacter and
      Providencia, was also found in MDPM. In four cases Salmonella enteritidis was
      also detected in the samples of both the skin of chicken carcasses and the MDPM.
      The nitrate salting mixture added at a concentration of 2% did not significantly
      reduce the counts of bacteria present in the MDPM. The prepared salami emulsion
      was very high in all groups of microorganisms, which was also caused by the
      addition of pork trimmings. This component seems to be a very important source of
      microbial contamination, showing the following average bacterial counts: total
      plate count 4.8 x 10(6)/g, the count of psychrotrophic bacteria 1.0 x 10(6)/g,
      the count of coliforms 7.0 x 10(5)/g, the count of Enterococci 9.2 x 10(3)/g, the
      count of Staphylococci 3.0 x 10(4)/g, the count of proteolytic microorganisms 2.7
      x 10(5)/g, and the count of lipolytic microorganisms 4.2 x 10(5)/g. However, heat
      treatment of the final product reliably and almost completely devitalized all the
      bacteria found in the salami emulsion before heat processing. No pathogenic or
      potentially pathogenic bacteria were detected in any sample of fine poultry
      salami. Quite a high number of bacteria in the salami emulsion was reduced by
      heat treatment to a final average value of 10(2)/g.

PMID- 9182396
TI  - [Identification of Citrobacter species and their occurrence in raw products and
      foods].
AB  - Fifty-nine strains of bacteria were tested in study that were isolated from raw
      materials and foods (raw milk, farm milking parlors, sausage meat, raw potatoes,
      cheese, frozen oven-ready foods, confectionery products, cold dishes), and they
      were included in the genus Citrobacter using a commercial diagnostic kit
      ENTEROtest 16 (Lachema a.s., Brno), numeric identification program TNW (Czech
      Collection of Microorganisms, Faculty of Science of Masaryk University at Brno)
      and identification key (O'Hara et al., 1995). The results of the ENTEROtest
      itself, including OXI and ONPtests, did not provide satisfactory discrimination
      of detected strains to the level of species since 64.4% were identified by the
      genus by TNW program or designated as intermediary strains. Correct species
      identification was obtained in 33.9% only (Tab. I). Five next conventional tests
      (dulcitol, alpha-methyl-glucoside, raffinose, melibiose, arginine dihydrolase)
      were used and their results successfully specified 94.9% tested strains to the
      species level (Tab. I). A dichotomic identification key (O'Hara et al., 1995)
      enabled to classify the strains on the basis of the results of ENTEROtest 16 and
      two conventional tests (dulcitol, melibiosis) relatively easily, and it can be
      recommended for routine identification of typical Citrobacters from foods. Only
      ten strains were classified in a wrong way (16.9%) due to false results in
      ENTEROtest (Tab. II). Tab. III shows the strains classified wrongly by both
      identifications systems. The tested set contained Citrobacter braakii in a
      majority of cases (30 strains), followed by C. freundii (17 strains), C. youngae
      (6 strains), 2 strains of genomospecies 10 and one strain of C. koseri, C.
      amalonaticus and C farmeri. Tab. IV shows the presence of Citrobacter species in
      the particular raw materials and foods. The most frequently present species in
      raw materials: C. braakii (26 strains, 68.4%), C. freundii (3 strains, 7.9%) and
      C. youngae (3 strains, 7.9%). Foods contained these three species only: C.
      freundii (14 strains, 66.7%), C. braakii (4 strains, 19.0%) and C. youngae (3
      strains, 14.3%). The percentage of the three most frequently present species in
      raw materials is substantially different from their percentage in foods (Fig. 1).
      The higher percentage of C. freundii presence in foods can be ascribed to
      secondary contamination.

PMID- 9182397
TI  - [A modern approach to developing anti-HIV vaccines].

PMID- 9182398
TI  - [A comparative analysis of proteins from persistent and antigen-defective strains
      of tick-borne encephalitis virus].
AB  - Structural (E) and three nonstructural (NS1, NS3, and NS5) proteins of persistent
      and antigen-defective strains of tick-borne encephalitis virus are compared by
      immunoblotting with monoclonal antibodies to the corresponding proteins of strain
      Sofyin. Appreciable phenotypical differences were revealed between antigen
      defective strains, but no immunological modifications as concerns the studied
      antigenic structures. The size of the reference NS3 protein differed from that of
      the persistent virus strains. Similar proteins detected in the antigenic
      preparations of strain Zausaev may have notable modifications.

PMID- 9182399
TI  - [Study of the phagocytic ability of blood polymorphonuclear leukocytes from
      rabbits and guinea pigs upon administering Ebola virus].
AB  - Study of the phagocytic activity of polymorphonuclear leukocytes (PMNL) of
      rabbits resistant to Ebola virus and guinea pigs susceptible to it, repeatedly
      challenged with live or inactivated Ebola virus in accordance with the
      immunization protocols, showed a much higher phagocytic activity in animals
      resistant to the virus than in those susceptible to it. Such behavior of PMNL in
      guinea pigs may be explained by the absence of the necessary cytokine background
      activating the neutrophils.

PMID- 9182400
TI  - [Preparation and characteristics of cultured strains of hepatitis A virus from
      humans and monkeys].
AB  - Cultural strains of hepatitis A virus (HAV) have been isolated from spontaneously
      infected Macaca mulatta (HAV-MM), Papio hamadryas (HAV-PH), African green monkeys
      Cercopithecus aethiops (HAV-CA), and patients (HAV-H). The strains replicate in
      continuous cells lines AGMK, 4647, Vero, and FRhk-4. AGMK and 4647 cells are the
      most permissive at 32 degrees C. Virus propagation was not associated with the
      cytopathic effect and could be detected by enzyme immunoassay (EIA), immune
      electron microscopy (IEM), and molecular hybridization method (MHM). The
      morphological and antigenic properties of the above monkey and human strains did
      not differ in EIA and IEM with polyclonal antibodies and for one most
      conservative genome sites in the VP1 domain. Cultural strains retained their
      pathogenicity for monkeys. HAV strains are proposed to be used as HAV antigen in
      immunological tests and for hepatitis A induction in monkeys.

PMID- 9182401
TI  - [Study of hepatitis E virus replication in FRhK-4 cell culture].
AB  - The cytolytic form of hepatitis E virus reproduction in FRhk-4 cells is
      described. The cytopathic effect was observed by days 6-7 of the 25th passage in
      this cell culture. Reverse transcription with polymerase chain reaction were used
      to study virus reproduction daily for 10 days postinfection. The virus
      replication starts on day 4 after inoculation. The development of the cytopathic
      effect depended on the serum concentration in culture medium, whereas the virus
      replication did not depend on this factor. The replicative form (-RNA) of viral
      RNA appeared on day 4 postinoculation, as did the new genomic one (+RNA).

PMID- 9182402
TI  - [False-positive reactions in laboratory diagnosis of Lassa, Marburg, and Ebola
      viral hemorrhagic fevers and AIDS].
AB  - Sera of normal subjects and AIDS patients living in Minsk and Odessa were tested
      for antibodies to hazardous viral infections Lassa, Marburg, and Ebola. Four to
      16% of examinees were seropositive to Ebola virus, 0.8 to 2.3% to Lassa, and up
      to 0.8% to Marburg virus. Common B-epitopes were found in viruses belonging to
      different families: Lassa, Ebola, and HIV. Antibodies specific to these viruses
      antigens were found in the reference sera to influenza A and B, respiratory
      syncytial virus, and adenovirus. Sera of convalescents after malaria and of AIDS
      patients contained antibodies to Lassa virus.

PMID- 9182403
TI  - [Development and study of immunoglobulins against Lassa fever].
AB  - The authors validate the use of horses as producers of immune antiserum to Lassa
      virus. Specific immunoglobulin with at least 1:512 titer of virus neutralizing
      antibodies to Lassa virus was obtained from the serum of immunized horses by
      Kohn's alcohol method. The resultant preparation does not differ from the
      heterologous commercial immunoglobulins. Preclinical studies of immunoglobulin
      against Lassa virus demonstrated its safety and high specific activity. The
      strategy of treating with the immunoglobulin alone and in combination with
      virasol has been experimentally validated.

PMID- 9182405
TI  - [Features of adult T-cell leukemia virus reproduction in B-cell lines and it's
      interaction with the Epstein-Barr herpesvirus].
AB  - Interaction between human T-cell leukemia virus (HTLV) with B cells and Epstein
      Barr virus (EBV) was studied by immunoblotting, immunofluorescence, virus
      isolation in permissive T-cell cultures, and polymerase chain reaction (PCR).
      HTLV-1 in vitro infects the B-cell cultures containing EBV but not EBV-negative
      cell lines. Productive infection of EBV+ B cells was associated with syncytium
      formation which led to the elimination of HTLV-1 producing cells. However, the
      remaining B-cell population contained gag, pol, and pX--the "silent" provirus
      sequences. HTLV-1 infection of B cells altered the expression of some latent
      proteins of EBV (EBNA-1, EBNA-2, EBNA-5, and LMP). The changes were represented
      by increase of molecular weight and/or appearance of additional proteins and were
      individual for each cell line. Alteration of EBV protein expression may change
      the functional activity of these proteins, but this hypothesis is to be tested.

PMID- 9182404
TI  - [Further study of hantavirus circulation in the Russian Federation].
AB  - Lung specimens of 1514 small mammals of 35 species captured in 1991-1995 at 9
      territories of Russia were tested in ELISA for virus antigens of hemorrhagic
      fever with the renal syndrome (HFRS). The antigens were detected in lung
      specimens of Clethrionomys glareolus, Microtus arvalis, Microtus gregalis,
      Microtus fortis, Arvicola terrestris, Apodemus agrarius, Micromys minutus, and
      Sorex sp., well known as Hantavirus reservoirs, captured in the Vologda,
      Yaroslavl, Saratov, Astrakhan, and Chita regions. Infection of Microtus
      maximoviczii revealed in the Chita region was first found in China. Previously
      there were no reports about the circulation of hantaviruses in this region. Our
      study added one more host to the list of HFRS virus hosts: Meliones tamariscinus.

PMID- 9182406
TI  - [Use of catalytic properties of iron-containing salts in immunoanalysis].
AB  - The possibility of using inorganic catalysts as markers for solid-phase
      immunoassay on the plates is shown with iron-containing hydrosols: ferrum
      hydroxide, ammonium ferriglycerate, and ferrum hydroxide modified with potassium
      ferrocyanide. Diagnostic agents based on iron-containing sols with dispersion of
      0.5 to 0.8 mm bound to immunoglobulins or staphylococcal protein A are no less
      sensitive than the immunoperoxidase agents, provided the same developing system
      is used (o-phenylenediamine + hydrogen peroxide). The sensitivity of solid-phase
      immunocatalytical assay of purified vaccinia and Venezuelan equine
      encephalomyelitis virus antigens was about 2 and 10 ng/ml, respectively. Hence,
      inorganic catalysts are prospective markers for immunoassay.

PMID- 9182407
TI  - [Isolation and characteristics of regional cytomegalovirus strains].
AB  - Two strains of cytomegalovirus were isolated from seropositive patients. The
      strains were identified and characterized by virological and immunological
      methods and may be used for research and practical studies.

PMID- 9182408
TI  - [Transgenerational transfer of gypsy moth (Ocneria dispar L.) nuclear
      polyhedrosis virus].
AB  - Gypsy moth nuclear polyhedrosis virus infects egg laying under natural
      conditions. The virus was identified by restriction endonucleases Pst1, BamH1,
      and Sal1.

PMID- 9182409
TI  - [Effect of inactivated Ebola virus on colony forming activity of human
      hematopoietic stem cells].
AB  - The effect of Ebola virus antigen on the growth of hemopoietic precursors was
      studied. Incubation of mononuclear cells with the viral antigen led to a dose
      dependent decrease of erythroid colony formation but did not alter the growth of
      the granulocyto-macrophagal precursors. Hence, Ebola virus antigen is capable of
      directly affecting the hemopoietic activity of precursors in man by inhibiting
      the growth of erythroid colonies.

PMID- 9182410
TI  - [The effect of "animal hypnosis" on the motor dominant created by the action of
      direct current on the cortex of the left hemisphere].
AB  - The state of "animal hypnosis" in rabbits was created by the DC current anode
      applied to the sensorimotor cortical area of the left hemisphere. It was
      impossible to elicit the "animal hypnosis" during the optimum of the dominant.
      The state of "animal hypnosis" could be easily elicited against the background of
      weak motor dominant on the next day after its creation. The "animal hypnosis"
      restored the "left" motor dominant after its extinction.

PMID- 9182411
TI  - [The EEG rhythms and psychological indices of emotions in reactive depression].
AB  - Power and topographic distribution of the EEG rhythms (delta, theta 1, theta 2,
      alpha, beta 1, and beta 2) were compared with the reactive and personal anxiety
      levels (by Spilberger) and parameters of subjective emotional semantic space
      (obtained by the method of subjective scaling). A general decrease in the EEG
      power was observed in reactive depression, with the exception of the theta
      rhythm, the power of which was higher than that in healthy persons. The increase
      in the theta 2 power in depression was correlated with activation of the right
      frontal area ("the zone of negative emotions"), and its decrease was associated
      with activation of the left frontal area ("responsible" for positive emotions),
      enhancement of positive emotions in semantic emotional space, and with a decrease
      in personal anxiety. High alpha activity in healthy persons was negatively
      correlated with the activation of the "zone of negative emotions" while a
      decrease in the alpha-rhythm power was associated with anxiety enhancement and
      decrease in contribution of positive emotions in the semantic space.

PMID- 9182412
TI  - [The contribution of presynaptic dopaminergic receptors to the mechanism of the
      reactivating influences of blockade of the GABA-benzodiazepine-ionophor complex].
AB  - The changes in reactivating efficiency of the GABA-benzodiazepine-ionophore
      complex blockade were examined in mice after preliminary activation or inhibition
      of dopamine autoreceptors by (+)3PPP (2 mg/kg) and haloperidol (0.01 mg/kg). The
      passive avoidance learning task and amnesia produced by detention of a mouse in
      the dangerous compartment were used. The pretest injections of bicuculline (1
      mg/kg), picrotoxin (1 mg/kg), and flumazenil (10 mg/kg) recovered the passive
      avoidance response in mice injected with saline before training. Pretreatment
      with the dopamine autoreceptor agonist and antagonist prevented from the recovery
      of amnestic memory trace induced by blockade of GABA-benzodiazepine-ionophore
      complex components. The results imply the involvement of dopamine/GABA-dependent
      mechanism in the modulation of memory trace retrieval.

PMID- 9182414
TI  - [Modification of the behavioral effects of corticoliberin by the early postnatal
      administration of corticosteroid hormones].
AB  - The action of intrastriatal administration of corticotropin-releasing hormone
      (CRH) on behaviour of male rats with early postnatal hydrocortisone injections
      was studied in open field experiments. Bilateral CRH administration into
      neostriatum significantly decreased the locomotor and exploratory activity. Rats
      which had been injected with hydrocortisone within the first 5 days of life were
      characterized by increased locomotion, but the anxiogenic action of CRH in these
      animals was not observed.

PMID- 9182413
TI  - [A comparative study of the taste sensitivity to phenylthiocarbamide in rats
      differing by the threshold of nervous system excitability].
AB  - Taste sensitivity to a bitter substance, phenylthiocarbamide (PTC) was studied in
      rat strains selected for the threshold of excitability of the nervous system. In
      the period of 17 days the drinking behaviour of the rats was estimated after
      giving them a series of PTC solutions with increasing concentrations and water as
      a control. The interstrain differences were found in the mean level of this index
      and its dynamics during the experimental period. Rats of the strain with high
      excitability showed the rhythmical changes of taste sensitivity to PTC related to
      the phases of moon rhythm. The obtained evidence points to relation between the
      sign under study and individual characteristics of the nervous system, namely,
      its excitability, and suggests the differences in activity of the second
      messenger system (Ca++, c-AMP and others) in the studied rat strains.

PMID- 9182415
TI  - [Ribonuclease improves the function of hippocampal slices in the postischemic
      period].
AB  - Population spike amplitude was measured in hippocampal slices under conditions of
      20-min glucose and oxygen deficit ("in vitro ischemia") with or without
      ribonuclease A. In control slices the response was gradually decreased within 3
      +/- 2 min after the onset of hypoxia/hypoglycemia. This process continued during
      13 +/- 6 min of reperfusion. The reperfusion restored the amplitude up to 70 +/-
      17% of its initial level within 1.5 h after the onset of this procedure. Addition
      of ribonuclease delayed the beginning of the response decrease (by 8 +/- 2 min)
      and increased the level of its restoration (up to 113 +/- 23%) after the
      reperfusion. It is suggested that ribonuclease prevents from the energy
      exhaustion by preserving the cellular energy stores.

PMID- 9182416
TI  - [The adaptive regulation of the nonlinear dynamics of brain electrical activity].
AB  - The reinforcing automated stimulation of the emotional positive hypothalamic
      areas which was contingent upon the multiperiodical events in the EEG structure
      increased the number of episodes with non-linear dynamics. It resulted in an
      increase in the frequency of the intracranial self-stimulation. Under conditions
      of controlled experiment a possibility was shown of the intentional experimental
      formation of the EEG episodes with different types of non-linear dynamics. At the
      stages preceding the associative learning, the application of fractal analysis
      enabled revealing a complex character of non-linearity in the bands of the EEG
      dominant frequencies with a slight tendency to a dominant process. The
      associative learning produced one dominant non-linear process which determined
      the dynamics of the whole system. The neurophysiological characteristics of the
      given adaptive process were determined as well as the difference between this
      process and the response to control stimulation.

PMID- 9182417
TI  - [The sensorimotor reaction time of preschool and young school-age children].

PMID- 9182418
TI  - [The forward formation of feedback conditioned connections during the development
      of a food-acquisition reflex].

PMID- 9182419
TI  - [The pain sensitivity thresholds of rats genetically selected for their rate of
      active avoidance acquisition].

PMID- 9182420
TI  - [The "pro" and "con" of the hypothesis of interimpulse intervalic information
      coding in the nervous system].
AB  - The present views are outlined on the principles of information code in the
      nervous system. It is shown that the frequency modulation of the rhythmical
      neuronal activity alone is unable to provide the processing and coding of the
      information necessary for cognitive activity. The fluctuation of the between
      impulse intervals which has been revealed by many authors is a treated as novel
      acquisition in the process of progressive evolution. The intervals and their
      various combinations as code signals can ensure the information processes
      simultaneously in a great number of neurons and synapses. The present state of
      neurophysiology and information theory don't enable an alternative hypothesis to
      be advanced.

PMID- 9182421
TI  - [Activation of the brain and consciousness].
AB  - At least 3 levels of consciousness were identified within the stage B of sleep.
      Against the background of the increase in the alpha-rhythm amplitude, we observed
      an enhancement of voluntary and involuntary associations and increase in the flow
      of thoughts. The stage of "thought wandering" was accompanied by a considerable
      decrease in the alpha-rhythm regularity, a decrease in its frequency, and
      decrease in EEG coherence in all brain areas under study. At the stage of the
      "flat" EEG, the subjects experienced inhibition of mental processes ("empty
      heady"), their consciousness as if "falling down" to the lowest Ego level. The
      subjects were aware of the transition from one stage to another and could fix the
      stages. Thus, the results showed that subjective changes of levels of
      consciousness corresponded to different stages of transition from wakefulness to
      sleep which was objectively determined by the EEG.

PMID- 9182422
TI  - [The characteristics of the reproduction of time intervals and the individual
      structure of the EEG in man].
AB  - The perception of time by humans was studied by the method of time reproduction.
      The EEG was recorded in Os, Od, Cs, Cd, Fs and Fd derivations. The relative EEG
      spectral power was determined in the delta-1, delta-2, theta, alpha, beta-1, and
      beta-2 ranges. All the subjects were divided in two groups: I--those who
      reproduced time-intervals with a delay, and II--those who were ahead in their
      reproduction. The spectral power of the delta-rhythm was significantly lower and
      that of the beta-rhythm higher in the subjects of the I than of the II group. In
      subjects of the II group total power of the beta range (beta-1 + beta-2) was
      significantly less than that in the delta-range (delta-1 + delta-2). This ratio
      was inverse in subjects of the I group. The described relationships were
      expressed both in the background EEG and during functional loads in all the
      studied derivations.

PMID- 9182424
TI  - [The perception of targeted signals in the auditory and somatosensory systems
      with a lesion of the brain stem].
AB  - Auditory and somatosensory evoked potentials (AEPs and SEPs) were recorded in 8
      patients with malignant processes in the brainstem region and 14 healthy persons
      under conditions of relevant and deviant stimulation. The spatial-temporal EP
      characteristics were evaluated and mapped. The low-voltage AEPs to simple
      rhythmical stimulation were recorded in patients over the whole cortical surface.
      During attention activation (solving selective attention tasks) there was an
      increase in the amplitude of the AEPs, mainly, of their mid-latency components.
      Under such conditions the N200 SEP components were well expressed in both
      hemispheres with the maximal amplitude in the medial and anterior derivations.
      The spatial distribution of N350 resembled that of the N200. There was an
      increase in N30 amplitude in both occipital derivations and its expressed
      reduction in the frontal areas as compared to the situation with the simple
      rhythmical stimulation. In patients with the brainstem pathology the increased
      amplitude of these components was observed mainly in the parietal and occipital
      cortical areas.

PMID- 9182423
TI  - [Topographic mapping of the process of synchronizing moments of sharp changes in
      the human multichannel EEG].
AB  - Techniques of evaluation were studied of the EEG synchronization between
      different EEG derivations in humans. It was shown that the pattern of cortical
      cooperativity constructed on the basis of classical EEG crosscorrelation and
      coherence could be substantially supplemented with estimations of coincidences of
      the moments of sharp changes (MSC) in multichannel EEG recording (the so called
      "operational synchronization"). The multichannel EEG was recorded in humans
      during memory task performance. A non-parametric technique was developed on the
      basis of the family of Kolmogorov-Smirnov's statistics for revealing the MSC in
      separate EEG realizations and subsequent spatial-temporal mapping of the MSC
      coincidences in different derivations of the multichannel EEG. It was shown that
      such maps markedly change depending on the current cognitive activity of the
      subjects. An attempt was made to interpret the estimations of the frequency and
      operational synchronization of multichannel human EEG.

PMID- 9182425
TI  - [The temporal correlations of the VEP of the visual and motor cortices during the
      perception and mental reproduction of an image in normal children and in those
      with intellectual disorders].
AB  - Temporal relations were analyzed between the VEP components in the occipital and
      central cortical areas in 7 and 10-year-old boys with normal intelligence, with
      mental retardation, and with debile oligophrenia in three experimental sessions
      with different instructions. It was found out that the intrahemispheric relations
      of the isopolar VEP components to a flash and patterned stimulus similar to those
      in adult persons developed in healthy children only to the age of 10 years. In
      children with intellectual deficiency such relations were distorted both in
      perception of the flash and patterned visual stimuli and during mental
      representation of the latter.

PMID- 9182426
TI  - [An evaluation of the high-frequency components of the brain's electrical
      activity by using inhomogeneity indices].
AB  - The qualitative techniques are considered of mathematical description of curve
      inhomogeneity which adequately reveal non-stationary fragments in EEG samples
      with a pseudorandom process. The introduced inhomogeneity coefficient turned to
      be a sufficiently adequate indicator of the presence of short-term high-frequency
      bursts in the electrical activity of dog's brain and a sensitive index for
      discrimination of quasihomogeneous fragments by the level of "general
      activation". It is shown that the values of this coefficient reflect the
      individual features of the brain electrical activity of the animals and its
      dynamics in the process of alimentary motor conditioning. At the same time, this
      index is ineffective in revealing the regional differences. A novel approach is
      developed for signal inhomogeneity description which is based on the traditional
      harmonic analysis (Fourier transform).

PMID- 9182427
TI  - [The effect of sodium nitrite on the realization of defensive and inhibitory
      conditioned reflexes].
AB  - After the administration of 11 mg/kg of sodium nitrite (NO of the generating
      drug) the motor disinhibition and increase in the myogram amplitude were observed
      in reaction of rabbits to non-reinforced flashes at the background of continuous
      light which served as a conditioned inhibitory signal (CIS). The disinhibition
      appeared within 1-1.5 h from he moment of NO administration and continued during
      the whole recording period (4 h). Under the NO dose of 5.5 mg/kg only the
      tendency was observed to motor disinhibition after the CIS presentation. The
      results obtained can be possibly explained by the NO ability to inhibit the
      functions of the GABA-ergic receptors, since it is known that elaboration of the
      internal inhibition is accompanied by an enhancement of the inhibitory
      hyperpolarizing processes realized with participation of the GABA-ergic
      transmitter system. Under the action on NO both in the small and doubled doses
      the myogram amplitude did not increase in response to combined presentation of
      the light flashes with pain reinforcement, in contrast to the repeated
      presentations of these paired stimuli in the control experiments. This phenomenon
      is probably determined by the inhibitory influence of NO on the NMDA receptors.

PMID- 9182428
TI  - [The effects of proactive interference in the task of spatial choice in a Y maze
      by rats].
AB  - The influence of the preceding conditioned reaction on the current conditioned
      performance was studied. Rats were trained to perform delayed and non-delayed
      spatial tasks in Y-maze. Two types of errors were analyzed: 1) the rats ran to
      the same maze arm as in the previous trial (errors of repetition), 2) the animals
      ran to the other arm (errors of alternation). It was shown that the alternation
      errors were more frequent under conditions of short intertrial interval and non
      delayed choice. The repetition errors occurred more frequently under conditions
      of long intertrial interval and delayed choice. The obtained evidence supports
      the idea that not only cue presentation and delay periods are important for
      successful performance but the whole structure of the task influences the complex
      organization of the behavioural acts.

PMID- 9182429
TI  - [The effect of the repeated experience of aggression in daily confrontations on
      the individual and social behavior of male mice].
AB  - The influence of repeated experience of aggression in daily intermale
      confrontations on individual and social behaviour was studied in male mice of
      C57BL/6J (C57) and CBA/Lac (CBA) strains. Repeated experience of aggression led
      to a decrease of emotionality in males of highly emotional CBA strain and
      increase in exploratory activity in the open field and exploratory activity
      tests, decrease of immobility time in Porsolt's test and pain sensitivity
      estimated by the "hot plate" test. Low emotional C57 males did not change their
      individual behaviour in different situations under the influence of repeated
      experience of aggression. However, aggressive C57 mice demonstrated anxiety-like
      behaviour estimated in the plus-maze test. In the partition test aggressive mice
      of both strains showed an increase in communicative level (as a reaction to a
      familiar male) in comparison with their behaviour before aggressive
      confrontations. Behavioural reaction to a receptive female under unfamiliar
      conditions decreased which testified to a decrease in sexual motivation. It is
      concluded that formation of the aggressive type of social behaviour is
      accompanied by changes in the individual and social behaviour of male mice.
      Characteristics of these changes are genetically determined and depend on the
      duration of confrontations.

PMID- 9182430
TI  - [The perceptual space of brightness in the monkey (the rhesus macaque)].
AB  - Brightness discrimination of black-white stimuli (1-37 Cd/m; CIE-31 chromatic
      coordinate X = 0.340, Y = 0.304) were studied using choice conditioning paradigm
      in two monkey (Macaque Rhesus). Confusion matrices were composed of probabilities
      of instrument responses to conditioned and differential stimuli in ten series in
      which one of the ten intensities was employed as a conditioned one. Confusion
      matrices were transformed into the correlation matrices between the vectors
      corresponding to the stimuli. Factor analysis of correlation matrices revealed
      two-dimensional circular structure of monkey's brightness perceptual space. This
      space was principally similar with that in humans, fishes, and rabbits. Two
      eigenvectors which constituted two-dimensional Euclidean space of brightness can
      be interpreted as bright and dark neuronal channels.

PMID- 9182431
TI  - [Aleksandr Grigor'evich Ginetsinskii (a biographical essay)].

PMID- 9182432
TI  - [The evolution of functions and functional evolution. 1961].

PMID- 9182433
TI  - [The contribution of A. G. Ginetsinskii to the theory of the chemical
      transmission of synaptic signals].

PMID- 9182434
TI  - [A. G. Ginetsinskii's hypothesis on the role of hyaluronidase in realizing the
      effect of the antidiuretic hormone].

PMID- 9182435
TI  - [A. G. Ginetsinskii and the development of the theory of osmoregulation].

PMID- 9182436
TI  - [The discovery by A. G. Ginetsinskii of the anticholinesterase mechanism of
      action of organophosphorus poisons].

PMID- 9182437
TI  - [The works of A. G. Ginetsinskii on the physiology of respiration].

PMID- 9182438
TI  - [A comparative study of the phospholipids and their fatty acid composition in
      different organs of mammals and fishes. The role of stereometry of the
      phospholipid molecules during the extraction of oxygen from the environment in
      these animal groups].

PMID- 9182439
TI  - [Evolution and consequences of changes in the interpretation of cancer].

PMID- 9182440
TI  - [Complications of radical nephrectomy in the treatment of kidney adenocarcinoma].
AB  - PURPOSE: To evaluate the peri- and post-surgical complications in Renal
      Adenocarcinoma (RAC) treated with Radical Nephrectomy (RN). MATERIAL AND METHOD:
      Revision of 109 patients with RAC who underwent transperitoneal anterior
      abdominal RN. Patients were locally staged post-surgically as: T1 + T2 61.5%, T3a
      22.9%, T3ab 11% and T3b 4.6%. Approach and conservation of homolateral suprarenal
      gland were decided based on the preferences of the performing urologist. Hilar
      lymphadenectomy was performed in all cases. RN was done by a staff member in 77%
      cases and by a training resident assisted by a staff member in the remaining 23%.
      RESULTS: Peri-operative complications occurred in 10% patients, most commonly
      with left RN (13% vs. 7%) (p = 0.1), and further within this group the most
      frequent ones occurred in those using midpoint laparotomy (17.8% vs. 4%) (p =
      0.1). Blood transfusion during surgery was required in 23% patients, this being
      more frequent when tumours had extended into the venous system (47%) and in left
      RN by midpoint laparotomy (39% vs. 12.5%) (p = 0.02). There were 32 post-surgical
      complications in 27 (24.8%) patients, the most common being sepsis of the
      surgical wound (6.4%); complications were more usual in patients undergoing right
      RN (31% vs. 20%) (p = 0.08) and in patients with blood transfusions (40% vs. 20%)
      (p = 0.4). There were no deaths. CONCLUSIONS: In our series, RN showed low
      intraoperative morbidity (10%), non-insignificant post-operative morbidity
      (24.8%) and no mortality. We consider subcostal laparotomy to be the best
      surgical approach in left RAC, with low morbidity and low peri-operative blood
      requirements.

PMID- 9182441
TI  - [Renal adenocarcinoma in young patients].
AB  - OBJECTIVE: To discover potential differences in known prognostic factors of renal
      adenocarcinoma in patients under 40 years of age. PATIENTS AND METHODS: A series
      of 246 patients with renal adenocarcinoma included 17 patients 40 years. Both
      groups were analyzed for sex, tumour size, histological characteristics and
      stage, examining the relative proportions within each group and looking for an
      association between those sets of data and age. RESULTS: No statistically
      significant associations were found, although it should be noted that in some
      cases data is incomplete. A larger proportion of low stages at least locally and
      a greater proportion of granule cell tumours was found in patients 40 years-old
      compared to those over 40. CONCLUSIONS: Existence of differences in the
      biological and histological characteristics of renal adenocarcinomas that develop
      at a younger age is not unlikely. The analysis of each factor and the survival
      rates in larger series should elucidate these questions, which will also be of
      interest to improve our understanding of the histogenesis of this type of
      tumours.

PMID- 9182442
TI  - [Systemic chemotherapy with cisplatin, methotrexate, and vinblastine, and bladder
      preservation in T2/T3a bladder cancer].
AB  - We are currently witnessing a lively controversy over which should be the optimal
      treatment for patients with infiltrant urothelial carcinoma with muscle location
      (stage B Jewett's Grading or T2-T3 on the TNM Rating Scale, UICC 1992). This
      paper reports a randomized, prospective study in 37 patients with T2-T3a tumours.
      Arm A (n = 20) received systemic chemotherapy with cisplatin, methotrexate and
      vinblastine (CMV) after TUR, and was carefully followed aiming for vesical
      preservation. Arm B (n = 17) was given chemotherapy with CMV after TUR and then
      underwent cystectomy. Disease-free survival at 5 years for the overall series is
      69%, 47% for group A and 88% for group B (log-rank, p = 0.14). No statistically
      significant differences in survival were detected relative to age (under or over
      65 years), growth patterns (papillary or plain), histological grade (G2 or G3),
      and size (smaller or greater than 5 cm). Survival was different depending on the
      clinical suspicion of nodular involvement (log-rank, p < 0.001). In summary,
      although the number of patients in the series does not allow to draw conclusions
      in terms of statistical significance, there is enough evidence to consider that
      vesical preservation based on TUR and systemic chemotherapy as definitive
      treatment is a dangerous option without the good survival rates achieved by
      T2/T3a patients undergoing cystectomy.

PMID- 9182443
TI  - [Limitations of ultrasonography in the clinical course monitoring of bladder
      tumors].
AB  - Ultrasonography is a fairly innocuous test in the follow-up of bladder tumours.
      Its results, however, can not be superposed to those of cystoscopy. This study
      aims to identify the risk factors for failure of transabdominal ultrasonography
      in the FU of bladder tumors. The influence of the primary tumour, sex and age of
      patients on the ability of ultrasonography to detect relapses was analyzed. Chi
      square and Student's t tests were used to associate the characteristics of
      primary tumours and patients to the results of ultrasonography. Student's t test
      was used to estimate the effect of diagnostic oversight in terms of annual
      recurrence rate and progression. The characteristics of primary tumours where
      relapse was detected or overlooked had no influence on the results of ultrasound
      follow-up as neither did age and sex. No differences were detected in recurrence
      rate of patients with anticipated (0.57) or overlooked (0.58) tumours. Although
      differences in progression rates (4.76% and 9% for overlooked and identified
      tumours, respectively) were substantial, they did not reach statistical
      significance. There are no features in the original tumour or the patient to
      anticipate the failure of ultrasound monitoring. Multiple and/or small relapses
      are overlooked more frequently that single and/or large ones, and tumours located
      in lateral walls, base and dome may be unnoticed. In spite of oversights,
      alternate ultrasound/cystoscopic monitoring does not compromise the outcome of
      the disease.

PMID- 9182444
TI  - [Relationship of prostatic carcinoma of the peripheral zone with glandular
      atrophy and prostatic intraepithelial neoplasia].
AB  - The study of the prostate's peripheral area in 32 patients, with age ranging
      between 48 to 75 years (mean, 61.4 +/- 6.7), demonstrates the frequency of
      certain morphological changes such as glandular atrophy (46.8%), which are
      neither related to age (p = 0.8) or the carcinoma (p = 0.8). A very different
      issue is the prostatic intraepithelial neoplasia, which although not
      statistically related to age in this series (p = 0.3) (probably due to the
      absence of young adults), appears to develop in earlier stages than cancer, is
      associated in 88.8% carcinomas (p = 0.03) and has a close topographic correlation
      to latent microscopic foci of adenocarcinoma of the prostate's peripheral area,
      anatomic proximity of both lesions occurring in 55.5% cases.

PMID- 9182445
TI  - [Suburethral sling in the treatment of urinary incontinence: our experience].
AB  - Review of 17 female patients who underwent placing of Suburethral Sling as anti
      incontinence procedure with the purpose of assessing the results obtained. The
      most frequent complications were urinary retention and post-surgical urgency. A
      larger proportion of patients with Stress Urinary Incontinence had retention and
      during more days than those with Mixed Urinary Incontinence. In most cases of
      mixed urinary incontinence, asymptomatic prior to surgery, the placing of a
      suburethral sling provokes signs and symptoms of urgency, and even of post
      surgical urgency-incontinence. Both complications were attenuated in all cases
      using measures such as conservation of urinary by-pass or administration of anti
      cholinergics. Results at 2 years have been successful in 68.75% cases, thus
      encouraging us to reduce the number of indications for this technique.

PMID- 9182447
TI  - [Bladder paraganglioma. Report of a case and review of the Spanish literature].
AB  - Paragangliomas are rare tumours of the bladder accounting for 0.06% of all
      vesical tumours. This paper reports one case of vesical paraganglioma in a young
      female patient that has the singularity of being associated to melanin
      pigmentation. A review is made of cases treated in Spain, adding some comments on
      the signs and symptoms presented, as well as the diagnostic and therapeutical
      methods used in this unusual condition.

PMID- 9182446
TI  - [Transitional tumor of the bladder in an teenager. Preliminary note].
AB  - Brief report on the case report of a young female diagnosed and treated (TUR) of
      a low grade transitional vesical tumour. The reason behind this paper is the
      early presentation of this tumoral species. Although this neoplasia used to be
      practically anecdotal, this is no longer the case. This fact prompted our concern
      and urged us to continue to investigate the reasons for vesical tumours having an
      increasingly higher incidence in our environment. In order to manage these
      neoplasias will shall merge data from ultrasonography with that obtained from
      urinary cytology. Cystoscopies shall be avoided as far as possible. References
      used to prepare this paper come from a brief review of the relevant Spanish
      urological literature. We believe this to be sufficient to prepare a "Clinical
      report" type original.

PMID- 9182448
TI  - [Bladder urothelial carcinoma in patients under 10 years of age: report of 2 new
      cases].
AB  - Contribution of two cases of vesical tumours in patients under 10 years. Up to
      date, some 25 cases have been described in the international literature; and some
      in the national literature. Due to their exceptional nature, we believe the
      contribution of these two new cases to be of interest.

PMID- 9182450
TI  - [Unusual association of transitional cell carcinoma in the upper urinary tract,
      with contralateral renal metastasis and renal lithiasis of long clinical course].
AB  - Presentation of a case reporting an infrequent association of transitional cell
      carcinoma of the upper urinary tract (UUT) with a long-standing renal
      polylithiasis and multifocal metastasis in contralateral kidney. A description is
      made of the incidence, etiology, prognostic factors as well as diagnosis and
      therapeutical approach.

PMID- 9182449
TI  - [Study of DNA content and its association with staging, tumor size, architecture,
      cell type, and nuclear grade in renal adenocarcinoma].
AB  - OBJECTIVE: To present the results of the analysis of DNA content in renal
      adenocarcinoma and its correlation with histopathological findings as a first
      step to conduct predictive studies. MATERIAL AND METHOD: DNA analysis was carried
      out by flow cytometry in deparaffined and fresh samples (1-4 per tumour) from 192
      tumours. Correlation to stage, size, growth pattern and grade was studied using
      the squared chi test. RESULTS: The percentage of non-diploid tumours increased
      with the number of samples analyzed. Use of multiple sampling allowed to classify
      as non-diploid an additional 19% tumours. 57% tumours were homogeneously diploid,
      while the rest were non-diploid showing a wide variety of patterns: homogeneous,
      heterogeneous, and even tumours with more than one different non-diploid
      population. A positive correlation was seen between DNA content pattern,
      pathological stage and grade. CONCLUSIONS: Multiple sampling is essential to
      obtain representative information on DNA content. Prior to conduct predictive
      studies, the correlation between DNA content, stage and grade should be studied
      to preclude addition of non-independent information.

PMID- 9182451
TI  - [Bladder pseudotumor in childhood].
AB  - Case report of a 10 year-old male with vesical mass suggestive of a
      rabdomiosarcoma based on the radiologic studies performed. The existence of an
      inflammatory process with no signs of malignancy was confirmed by transurethral
      resection. The serological studies were negative and the absence of malignant
      disease in further substantiated by immunohistochemistry. We want to emphasize
      that certain vesical masses. which appear to be malignant on the radiological
      study (Pseudotumours), may be just inflammatory processes.

PMID- 9182452
TI  - [Dermatomyositis and small cell tumor of the kidney].
AB  - Dermatomyositis is an inflammation of the striated muscle with an important
      leukocyte infiltrate which is accompanied by a characteristic cutaneous
      exanthema. In the international classification we find DM associated with
      neoplasm in 10% of cases. It is accepted that neoplasms are related to DM if it
      does not exceed it in two years (prior o after the onset of the disease. The most
      commonly associated are lung, ovary and breast cancers. In the pas ten years only
      two cases of DM associated to renal cancer (both in renal cell cancers) have been
      published. In this article we present a case history of a woman with a DM
      associated to a renal oat-cell carcinoma. Also, we will review the literature on
      this theme and will evaluate the predictive parameters of the presence of
      malignancies in this pathology.

PMID- 9182453
TI  - [Extraction of yuxtaureteral suture, with ureteroscopy. A clinical case].
AB  - Presentation of one case of ureteroscopical removal of a yuxtaureterateral suture
      which was causing ureterohydronephrosis. Following that procedure both the
      morphology and the function of the renoureteral unit involved returned to normal.
      In ureteral lesions of late discovery, ureteroscopy may be in specific cases a
      resolutive therapeutical option.

PMID- 9182454
TI  - [Bilateral abscess of cavernous bodies].
AB  - Report of a rare case of abscess in both cavernous bodies. Its peculiarity is
      based on the location, the bilateral nature and the absence of a clear causative
      factor, although it was probably related of a local septic focus (rectal or
      prostatic). Diagnosis was established with CAT because of the primarily posterior
      location and the significant peripheral inflammatory reaction. The patient was
      treated successful with a vigorous antibiotic therapy and open drainage from both
      cavernous bodies with no development of sequelae such as fibrosis and penial
      incurvation or impotence.

PMID- 9182455
TI  - [Acute scrotum: unusual presentation of Schonlein-Henoch purpura].
AB  - Being a systemic vasculitis, Schoenlein-Henoch purpura may affect the scrotum and
      its content. According to the series studied, this occurs in about 10% patients
      (2-38%) and sometimes requires a differential diagnosis with the spermatic cord
      torsion. An isotopic study with 99Tc may avoid a surgical procedure quite often
      unnecessary. In the case reported here, vasculitis presented as an acute scrotum,
      which is highly infrequent in the literature and makes a correct presumption
      diagnosis extraordinary difficult.

PMID- 9182456
TI  - [Value of Doppler ultrasonography in the diagnosis of venogenic erectile
      dysfunction].

PMID- 9182457
TI  - Genetics, alcohol, and cirrhosis.

PMID- 9182458
TI  - Control of vancomycin-resistant enterococcus.

PMID- 9182459
TI  - Antibiotic prophylaxis before endoscopic retrograde cholangiopancreatography.

PMID- 9182460
TI  - Hepatitis G and mixed cryoglobulinemia.

PMID- 9182461
TI  - Hepatitis C and cancer.

PMID- 9182462
TI  - Anticardiolipin antibodies and physical disability in the elderly.

PMID- 9182463
TI  - Bedside prediction of Clostridium difficile colitis.

PMID- 9182464
TI  - Update in critical care medicine.

PMID- 9182465
TI  - Lymphocyte subsets in severe atherosclerosis before revascularization.

PMID- 9182466
TI  - Smoking and autoimmune thyroid disease.

PMID- 9182467
TI  - Postoperative hyponatremia.

PMID- 9182468
TI  - Over-the-counter naproxen sodium and esophageal injury.

PMID- 9182469
TI  - Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves
      assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology
      Substudy Team.
AB  - BACKGROUND: CD4+ lymphocyte counts and plasma HIV-1 RNA levels predict
      progression of HIV-related disease, but the relative importance of these and
      other virological factors in defining response to antiretroviral therapy is not
      yet clear. OBJECTIVE: To determine the short-term variability of plasma HIV-1 RNA
      level during stable therapy; the relative importance of pretreatment values and
      early changes in CD4+ count, HIV-1 RNA levels, and infectious HIV-1 titers in
      mononuclear cells of peripheral blood and pretreatment syncytium-inducing
      phenotype of an HIV-1 isolate for prediction of disease progression and decline
      in CD4+ counts during therapy. DESIGN: Data were collected prospectively in a
      randomized, clinical trial comparing two combination regimens (ACTG [AIDS
      Clinical Trials Group] Protocol 241) and pooled across treatments. SETTING: 8
      AIDS Clinical Trials Units. PATIENTS: 198 adults with HIV-1 infection and no more
      than 350 CD4+ lymphocytes/mm3 who had received at least 6 months of nucleoside
      therapy. INTERVENTIONS: All patients received zidovudine and didanosine; 100
      received nevirapine and 98 received placebo. MEASUREMENTS: CD4+ lymphocyte
      counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were
      measured before and 8 and 48 weeks after study treatment. Assay for the syncytium
      inducing viral phenotype was done at baseline. Progression was defined as
      occurrence of opportunistic infection, malignancy, or death during the 48 weeks
      after treatment began. RESULTS: The difference between two measurements of HIV-1
      RNA levels at baseline was within +/-0.39 log10 copies/mL (2.5-fold) for 90% of
      167 patients receiving stable therapy. In a multivariate model, risk for disease
      progression was reduced by 56% (95% CI, 8% to 79% [P = 0.028]) for every 10-fold
      lower HIV-1 RNA level at baseline, by 52% (CI, 6% increase to 79% reduction [P =
      0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after treatment
      initiation, and by 67% (CI, 42% to 81% [P < 0.001]) for every 2-fold higher CD4+
      count at baseline. These risk factors and syncytium-inducing viral phenotype at
      baseline, but not infectious HIV-1 titers in circulating cells, were associated
      with change in CD4+ counts over 48 weeks. CONCLUSIONS: For an individual patient,
      a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true
      biological change. Monitoring HIV-1 RNA levels and CD4+ lymphocytes before a
      change in antiretroviral treatment and monitoring HIV-1 RNA levels shortly
      thereafter improves prediction of disease progression and decline in CD4+ counts
      for 1 year compared with monitoring CD4+ counts of HIV-1 RNA levels alone.
      Additional monitoring of infectious HIV-1 titers in mononuclear cells of
      peripheral blood is not useful.

PMID- 9182471
TI  - Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection.
AB  - BACKGROUND: The rate of disease progression among persons infected with human
      immunodeficiency virus type 1 (HIV-1) varies widely, and the relative prognostic
      value of markers of disease activity has not been defined. OBJECTIVE: To compare
      clinical, serologic, cellular, and virologic markers for their ability to predict
      progression to the acquired immunodeficiency syndrome (AIDS) and death during a
      10-year period. DESIGN: Prospective, multicenter cohort study. SETTING: Four
      university-based clinical centers participating in the Multicenter AIDS Cohort
      Study. PATIENTS: 1604 men infected with HIV-1. MEASUREMENTS: The markers compared
      were oral candidiasis (thrush) or fever; serum neopterin levels; serum beta 2
      microglobulin levels; number and percentage of CD3+, CD4+, and CD8+ lymphocytes;
      and plasma viral load, which was measured as the concentration of HIV-1 RNA found
      using a sensitive branched-DNA signal-amplification assay. RESULTS: Plasma viral
      load was the single best predictor of progression to AIDS and death, followed (in
      order of predictive strength) by CD4+ lymphocyte count and serum neopterin
      levels, serum beta 2-microglobulin levels, and thrush or fever. Plasma viral load
      discriminated risk at all levels of CD4+ lymphocyte counts and predicted their
      subsequent rate of decline. Five risk categories were defined by plasma HIV-1 RNA
      concentrations: 500 copies/mL or less, 501 to 3000 copies/mL, 3001 to 10000
      copies/mL, 10001 to 30000 copies/mL, and more than 30000 copies/mL. Highly
      significant (P < 0.001) differences in the percentages of participants who
      progressed to AIDS within 6 years were seen in the five risk categories: 5.4%,
      16.6%, 31.7%, 55.2%, and 80.0%, respectively. Highly significant (P < 0.001)
      differences in the percentages of participants who died of AIDS within 6 years
      were also seen in the five risk categories: 0.9%, 6.3%, 18.1%, 34.9%, and 69.5%,
      respectively. A regression tree incorporating both HIV-1 RNA measurements and
      CD4+ lymphocyte counts provided better discrimination of outcome than did either
      marker alone; use of both variables defined categories of risk for AIDS within 6
      years that ranged from less than 2% to 98%. CONCLUSIONS: Plasma viral load
      strongly predicts the rate of decrease in CD4+ lymphocyte count and progression
      to AIDS and death, but the prognosis of HIV-infected persons is more accurately
      defined by combined measurement of plasma HIV-1 RNA and CD4+ lymphocytes.

PMID- 9182470
TI  - Changes in plasma HIV RNA levels and CD4+ lymphocyte counts predict both response
      to antiretroviral therapy and therapeutic failure. VA Cooperative Study Group on
      AIDS.
AB  - BACKGROUND: Markers are needed for assessing response to antiretroviral therapy
      over time. The CD4+ lymphocyte count is one such surrogate, but it is relatively
      weak. OBJECTIVE: To assess the association of changes in plasma human
      immunodeficiency virus (HIV) RNA level and CD4+ lymphocyte count with progression
      to the acquired immunodeficiency syndrome (AIDS). DESIGN: Analysis of data from a
      subset of patients in a multicenter, randomized, clinical trial. SETTING: Six
      Veterans Affairs medical centers and one U.S. Army medical center. PATIENTS: 270
      symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on
      AIDS. INTERVENTION: Patients were randomly assigned to receive zidovudine or
      placebo initially; a cross-over protocol was established for patients receiving
      placebo who had disease progression. MEASUREMENTS: Reverse transcriptase
      polymerase chain reaction on cryopreserved plasma samples, previously obtained
      CD4+ lymphocyte counts, and clinical events. RESULTS: For each decrease of 0.5
      log10 copies/mL in plasma HIV RNA level, averaged over the 6 months after
      randomization, the relative risk (RR) for progression to AIDS was 0.67 (P <
      0.001). In a subset of 70 treated patients with long-term follow-up, a return to
      baseline plasma HIV RNA levels within 6 months of randomization was associated
      with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4+
      lymphocyte counts over time were more strongly associated with progression to
      AIDS than were baseline levels or counts. CONCLUSIONS: An adequate virologic
      response after initiation of antiretroviral therapy seems to require a decrease
      in plasma HIV RNA level of at least 0.5 log10 copies/mL that is sustained for at
      least 6 months. The independent relation between plasma HIV RNA level and CD4+
      lymphocyte count over time and clinical outcome suggests that the measurement of
      plasma HIV RNA level, in addition to the CD4+ lymphocyte count, has a role in
      guiding the management of antiretroviral therapy.

PMID- 9182472
TI  - Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin
      dependent diabetes mellitus and hypertension. A randomized, controlled trial.
AB  - BACKGROUND: Diabetic patients are considered less suitable than nondiabetic
      patients for beta-blocker therapy because of the risk for worsened glucose and
      lipid metabolism and more severe hypoglycemic attacks. OBJECTIVE: To compare the
      metabolic and cardiovascular effects of carvedilol with those of atenolol in
      diabetic patients with hypertension. DESIGN: Randomized, double-blind, 24-week
      trial. SETTING: University hospital clinic. PATIENTS: 45 patients with non
      insulin-dependent diabetes mellitus and hypertension. INTERVENTION: After a 4- to
      6-week run-in period during which placebo was given in a single-blind manner,
      patients were randomly assigned to carvedilol or atenolol. MEASUREMENTS: An oral
      glucose tolerance test; assessment of insulin sensitivity and hormonal responses
      to insulin hypoglycemia; and assessment of lipid levels, blood pressure, left
      ventricular mass, and lipid peroxidation. RESULTS: Changes in systolic and
      diastolic blood pressure and left ventricular mass index were similar with
      carvedilol and atenolol (P > 0.2). Fasting plasma glucose and insulin levels
      decreased with carvedilol and increased with atenolol. Responses to carvedilol
      were greater than those to atenolol, as follows: increase in total glucose
      disposal, 9.54 mumol/kg of body weight per minute (95% CI, 7 to 11.9 mumol/kg per
      minute); decrease in plasma glucose response to oral glucose, 61 mmol/L x 180
      minutes (CI, -101 to -21 mmol/L x 180 minutes); decrease in insulin response to
      oral glucose, 6.2 nmol/L x 180 minutes (CI, -9.8 to -2.6 nmol/L x 180 minutes);
      decrease in triglyceride level, 0.56 mmol/L (CI, -0.75 to -0.37 mmol/L; P <
      0.001); increase in high-density lipoprotein cholesterol level, 0.13 mmol/L (CI,
      0.09 to 0.17 mmol/L; P < 0.001); and decrease in lipid peroxidation, 0.25 mumol/L
      (CI, -0.34 to -0.16 mumol/L). CONCLUSIONS: By improving glucose and lipid
      metabolism and reducing lipid peroxidation, carvedilol may offer advantages in
      patients with diabetes and hypertension.

PMID- 9182473
TI  - Correction of excessive anticoagulation with low-dose oral vitamin K1.
AB  - BACKGROUND: Despite earlier acceptance of oral vitamin K1 (phytonadione) for the
      treatment of excessive anticoagulation, some recent guidelines do not recommend
      its use. OBJECTIVE: To reevaluate the efficacy of oral vitamin K1 in correcting
      excessive anticoagulation. DESIGN: Case series. SETTING: Anticoagulation clinics
      at two university medical centers. PATIENTS: 81 outpatients who had an
      international normalized ratio (INR) greater than 5.0 but did not have
      significant bleeding. INTERVENTIONS: Withholding 1 or 2 doses of warfarin,
      administering 2.5 mg of oral vitamin K1, measuring the INR after 24 to 48 hours,
      and adjusting the warfarin dose. MEASUREMENTS: INRs were obtained from a portable
      capillary fingerstick monitor or from an automated photooptical coagulometer.
      RESULTS: In 68 of 71 patients (96%), oral vitamin K1 lowered the INR from between
      5.0 and 10.0 to less than 5.0 without inducing resistance to further
      anticoagulation. CONCLUSIONS: Withholding 1 or 2 doses of warfarin and
      administering 2.5 mg of oral vitamin K1 is a reliable, safe, and inexpensive way
      to rapidly correct excessive anticoagulation (INR > 5.0) in patients who do not
      have serious bleeding episodes and have an INR of less than 10.0.

PMID- 9182474
TI  - Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian
      soldiers. A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Mefloquine and doxycycline are the two drugs recommended for
      prophylaxis of malaria for visitors to areas where Plasmodium falciparum is
      resistant to chloroquine. OBJECTIVE: To compare the efficacy and tolerability of
      mefloquine with those of doxycycline as prophylaxis for malaria. DESIGN:
      Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of
      malaria. SETTING: Northeastern Irian Jaya, Indonesia. PARTICIPANTS: 204
      Indonesian soldiers. INTERVENTION: After radical curative treatment, participants
      were randomly assigned to receive 100 mg of doxycycline per day and mefloquine
      placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d
      for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis
      lasted approximately 13 weeks. MEASUREMENTS: The primary end point for efficacy
      was the first occurrence of malaria, as documented by a positive malaria smear.
      Malaria smears were obtained weekly and when patients had symptoms suggesting
      malaria. Reported symptoms were recorded daily, and an exit study questionnaire
      was conducted. RESULTS: In the placebo group, 53 of 69 soldiers developed malaria
      (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95%
      CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of
      cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68
      soldiers (16.9 person-years) in the mefloquine group; thus, the protective
      efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P.
      falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a
      protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well
      tolerated. CONCLUSIONS: Mefloquine and doxycycline were both highly efficacious
      and well tolerated as prophylaxis of malaria in Indonesian soldiers.

PMID- 9182475
TI  - Homelessness: care, prevention, and public policy.
AB  - Homeless men, women, and children make up a growing population that is vulnerable
      to preventable disease, progressive morbidity, and premature death. Homelessness
      and poverty are inextricably linked, and subgroups of persons who live in poverty
      have a particularly high risk for becoming homeless. Providing effective primary
      care for homeless persons is a formidable task because of many internal and
      external barriers to care. Targeted care strategies and new approaches to primary
      care are required to lower these barriers. Effective disease prevention in the
      homeless requires effective programs and policies to prevent homelessness. It is
      imperative that health professionals, the societies to which they belong, and
      academic health systems reaffirm their social responsibility, commit to changing
      public policies that perpetuate homelessness, and assist in the development and
      provision of primary health care services for persons who are homeless or on the
      brink of homelessness.

PMID- 9182476
TI  - Medical scientists and health news reporting: a case of miscommunication.
AB  - The public is poorly served by the coverage of medical science in the general
      press. Scientists and physicians blame the press, claiming that journalists are
      careless in their reporting, subject to competitive pressures, and ignorant of
      the scientific process. Journalists accuse the medical community of limiting
      access to information and erecting barriers to the public dissemination of
      medical research. In many areas of health news reporting, the underlying problem
      is an interactive dynamic that involves scientists and journalists. Both parties
      share the responsibility for accurate communication to the public. This report
      suggests ways to improve health news reporting, focusing on four problem areas:
      sensationalism, biases and conflicts of interest, lack of follow-up, and stories
      that are not covered.

PMID- 9182477
TI  - Use of HIV viral load in clinical practice: back to the future.

PMID- 9182478
TI  - Where's the bias?

PMID- 9182480
TI  - What's wrong with this picture?

PMID- 9182479
TI  - Diagnosing syncope. Part 1: Value of history, physical examination, and
      electrocardiography. Clinical Efficacy Assessment Project of the American College
      of Physicians.
AB  - PURPOSE: To review the literature on diagnostic testing in syncope and provide
      recommendations for a comprehensive, cost-effective approach to establishing its
      cause. DATA SOURCES: Studies were identified through a MEDLINE search (1980 to
      present) and a manual review of bibliographies of identified articles. STUDY
      SELECTION: Papers were eligible if they addressed diagnostic testing in syncope
      or near syncope and reported results for at least 10 patients. DATA EXTRACTION:
      The usefulness of tests was assessed by calculating diagnostic yield: the number
      of patients with diagnostically positive test results divided by the number of
      patients tested or, in the case of monitoring studies, the sum of true-positive
      and true-negative test results divided by the number of patients tested. DATA
      SYNTHESIS: Despite the absence of a diagnostic gold standard and the paucity of
      data from randomized trials, several points emerge. First, history, physical
      examination, and electrocardiography are the core of the syncope workup (combined
      diagnostic yield, 50%). Second, neurologic testing is rarely helpful unless
      additional neurologic signs or symptoms are present (diagnostic yield of
      electroencephalography, computed tomography, and Doppler ultrasonography, 2% to
      6%). Third, patients in whom heart disease is known or suspected or those with
      exertional syncope are at higher risk for adverse outcomes and should have
      cardiac testing, including echocardiography, stress testing. Holter monitoring,
      or intracardiac electrophysiologic studies, alone or in combination (diagnostic
      yields, 5% to 35%). Fourth, syncope in the elderly often results from
      polypharmacy and abnormal physiologic responses to daily events. Fifth, long-term
      loop electrocardiography (diagnostic yield, 25% to 35%) and tilt testing
      (diagnostic yield < or = 60%) are most useful in patients with recurrent syncope
      in whom heart disease is not suspected. Sixth, psychiatric evaluation can detect
      mental disorders associated with syncope in up to 25% of cases. Seventh,
      hospitalization may be indicated for patients at high risk for cardiac syncope
      (those with an abnormal electrocardiogram, organic heart disease, chest pain,
      history of arrhythmia, age > 70 years) or with acute neurologic signs.
      CONCLUSIONS: Many tests for syncope have a low diagnostic yield. A careful
      history, physical examination, and electrocardiography will provide a diagnosis
      or determine whether diagnostic testing is necessary in most patients.

PMID- 9182481
TI  - Value of technetium-99m pertechnetate imaging in the differential of salivary
      gland lesions.

PMID- 9182482
TI  - Surgery on the Internet. Part 1: The origins of the Internet.
AB  - The last few years have seen a dramatic increase in the size and use of the
      Internet; indeed recent figures estimate that the number of people with Internet
      access is increasing by up to 20 per cent monthly with over 30 million people now
      connected world wide. Many organisations, including The Royal College of Surgeons
      of England, now offer their own world wide web (WWW) sites. There are a number of
      areas and facilities on the Internet which are of particular interest to the
      surgeon; these include access to journals and textbooks, information of surgical
      units world-wide, e-mail and newsgroups discussing various surgical topics. The
      aim of this article, together with the two others in the series is to explain the
      steps necessary to get connected to the Internet and to illustrate some of the
      main areas of interest to the surgeon. This, the first of the articles will
      describe the origins of the Internet and the equipment and process required to
      get connected.

PMID- 9182483
TI  - [Internet for urologists].

PMID- 9182484
TI  - [Survival in stage T2-T3A bladder cancer treated with radical cystectomy].
AB  - OBJECTIVE: The optimal treatment for patients with localized muscle-infiltrating
      urothelial carcinoma (Jewett stage B or T2-T3a of the TNM classification, UICC
      1992) continues to be a controversy. The present study analyzed the survival rate
      in patients with stage T2-T3a bladder cancer who had been treated by radical
      cystectomy. METHODS: The records of 50 patients with T2-T3a NO tumor, submitted
      to pelvic lymphadenectomy and radical cystoprostatectomy, were reviewed to
      determine the prognosis in this group of patients. Seventeen patients (34%)
      received three courses of systemic chemotherapy (CMV) prior to cystectomy.
      RESULTS: The overall 5-year survival rate was 73%; 76% for those with T2 (n = 30)
      and 67% for those with T3a (n = 20) (log-rank, p = 0.27). No statistically
      significant differences were observed for age (less than or over 65 years), tumor
      growth pattern (papillary or flat), tumor size (less or greater than 5 cms) or
      treatment (with or without induction CMV). However, patients with G1-2 tumor had
      a better survival rate (94% at 5 years) than those with G3 tumor (51%), a
      difference with statistical significance (log-rank, p = 0.047). The Cox
      regression analysis showed no independent variable of prognostic significance.
      CONCLUSION: Muscle-infiltrating urothelial carcinoma is highly curable by radical
      surgery. Some authors believe it is unnecessary to distinguish T2-T3a lesions;
      therefore a critical review of the TNM classification appears to be warranted. We
      are unable to distinguish patients with a better prognosis that might benefit
      from less aggressive therapeutic options. Similarly, the therapeutic benefits of
      induction chemotherapy prior to cystectomy in patients with stage T2-T3a tumor
      could not be demonstrated.

PMID- 9182485
TI  - [Renal tumors smaller that 3 cm].
AB  - OBJECTIVES: To analyze the characteristics of renal adenocarcinoma less than 3 cm
      in size and to determine the therapeutic approach in these tumors. METHODS: 286
      cases with a histological diagnosis of renal adenocarcinoma that had undergone
      surgery at our hospital over the last 25 years were reviewed. RESULTS: The study
      showed 11 cases had renal tumors less than 3 cm in size. Six had been
      incidentally diagnosed. Two patients presented metastasis during the course of
      the disease and one patient had massive lymph node invasion (N3) at the time of
      diagnosis. Seven patients had a low tumor stage and grade. CONCLUSION: Renal
      tumors less than 3 cm in size have been considered to have a low potential for
      malignancy. However, the availability of more sophisticated diagnostic imaging
      techniques have led to earlier detection of renal masses, when the tumor is of a
      smaller size. Therefore determining whether the tumor is benign or malignant
      should be based exclusively on the histopathological findings. Treatment of this
      type of lesions is by surgery and performing a partial nephrectomy should be
      considered.

PMID- 9182486
TI  - [Value of PSA and (pre- postoperative) Gleason in predicting the potential
      lymphatic involvement in patients with prostatic cancer].
AB  - OBJECTIVE: To determine the possibility of selecting patients at risk for lymph
      node involvement prior to radical prostatectomy utilizing PSA concentration
      and/or the Gleason score. METHODS: We reviewed the records of 52 patients with
      tumor stage T1 to T3, who had undergone lymphadenectomy; of these, 50 patients
      underwent radical prostatectomy. The predictive values for PSA and the Gleason
      score and their utility in predicting risk of lymph node involvement were
      analyzed. RESULTS: Of the 52 patients, 10 (19%) had lymph node involvement. Nine
      of 26 patients (35%) with PSA > 20 and 9 of 21 patients (42%) with a Gleason
      score > 7 had lymph node involvement. No patient with PSA < 15 or Gleason score <
      5 and none of the 24 patients (57%) with PSA < 20 and Gleason score < 7 had lymph
      node involvement. The preoperative biopsy was understaged in 21 patients (41%);
      of these, 16% had a Gleason score of 5-6. Two of these patients with PSA > 20
      micrograms/ml had lymph node involvement. CONCLUSION: PSA concentration and the
      Gleason score are useful in predicting the risk of lymph node involvement.
      Patients with PSA < 20 and a Gleason score of < 7 can be considered to be at no
      risk and staging lymphadenectomy could be unnecessary. Although the preoperative
      Gleason score appears to have a predictive value, the possibility of understaging
      should be taken into account. In this regard PSA can be useful in identifying
      those patients at risk.

PMID- 9182487
TI  - [Correlation between prostate specific antigen and histopathologic findings in
      ileum-obturator node dissection].
AB  - OBJECTIVE: To determine the correlation between PSA values and the
      histopathological findings of ileo-obturator node dissection in prostatic cancer.
      METHODS: We reviewed the data of 51 patients with clinically localized prostatic
      carcinoma, submitted to ileo-obturator node dissection before definitive
      treatment of the tumor. The patients were classified into 4 groups according to
      their previous PSA values: A < 10 ng/ml, B > 10 and < 20 ng/ml, C > 20 and < 50
      ng/ml and D < 50 ng/ml. RESULTS: Overall 17.6% of the patients had positive lymph
      nodes; 9.9% of the patients in group A, 15.4% of the patients in group B, 11.1%
      of those in group C and 41.7% of those in group D had positive nodes. Using 50
      ng/ml as the cut-off point, 10% of those with PSA < 50 ng/ml had positive nodes
      vs 42.3% of those with PSA > 50 ng/ml, which was statistically significant with
      the Fischer test. CONCLUSION: Preoperative PSA has a statistically significant
      correlation with positive nodes, considering 50 ng/ml as the cut-off point. PSA
      determination in patients that have received no treatment is essential in the
      diagnosis and evaluation of therapy in prostate cancer.

PMID- 9182488
TI  - [Usefulness of ultrasonography in the assessment of acute pyelonephritis].
AB  - OBJECTIVE: The diagnosis of acute pyelonephritis (APN) is based fundamentally on
      the clinical and bacteriological findings. Radiology is useful in ruling out
      obstructive causes that often require surgical management. The present study
      analyzed the role of renal ultrasonography (US) in patients with clinical
      symptoms, signs and history compatible with APN that have normal plain abdominal
      x-rays. METHODS: 87 patients who consulted our emergency services with symptoms
      and signs compatible with APN were reviewed. Patients who referred renal colic
      and those with a previous history of urological disease other than uncomplicated
      recurrent urinary tract infection were excluded. Patients with a plain abdominal
      x-ray compatible with lithiasis were excluded. Renal US evaluation was performed
      by the urologist to rule out hydronephrosis. RESULTS: 37 (42.5%) of the 87
      patients had an abnormal US scan. These patients were evaluated again by US or
      IVP, or both (one case). Obstructive uropathy was demonstrated in only 5 cases
      (5.8%). These foregoing 5 patients were treated by surgery. CONCLUSIONS: In our
      series, renal US evaluation indicated surgical treatment in 5.8% of patients with
      clinical features of APN and a plain abdominal x-ray with no evidence of
      lithiasis. This incidence is likely to be lower in the outpatient setting. It is
      difficult to propose a standard approach in the management of these patients. It
      may therefore be more reasonable to utilize US and IVP in those patients who do
      not respond to antibiotic therapy.

PMID- 9182489
TI  - [Scrotal granuloma caused by oil migrating from the hip in 2 transsexual males
      (scrotal sclerosing lipogranuloma)].
AB  - OBJECTIVE: To describe two patients with scrotal granuloma due to silicone oil
      migrated from the hip. METHODS/RESULTS: Two male transsexuals without
      genitoplasty developed scrotal inflammatory masses after subcutaneous injection
      of silicone oil to remodel the hip contour. Imaging studies and pathologic
      examination disclosed lesions similar to those encountered in ruptured silicone
      breast implants. CONCLUSIONS: Silicone migration to the scrotum through subdermal
      fascial planes can cause a granulomatous lesion similar to that of ruptured
      breast implants. The migratory pathway is similar to that of scrotal emphysema
      and, inversely, the dissemination of necrotizing fasciitis of the genitalia.

PMID- 9182490
TI  - [Surgical repair of vesico-vaginal fistulae with abdominal-transvesical approach.
      Comments on this technique and long-term results].
AB  - OBJECTIVES: We reviewed our series of vesicovaginal fistula that had been treated
      by the abdominal-transvesical approach, which we have also utilized in complex
      relapsed fistulas of the posterior aspect of the bladder in all but one case of
      triple fistula associated with lithiasis of the bladder. METHODS: 6 patients with
      vesicovaginal fistula secondary to pelviogynecological surgery were treated by
      the abdominal-transvesical approach. One patient had been referred to our
      hospital for a triple fistula that had relapsed for the fifth time. This patient
      was submitted to cystolithotomy during the same session. Another patient with
      urinary incontinence and cystocele prior to the fistula underwent
      unrethrocervicopexy following the Marshall-Marchetti-Krantz technique after
      fistula repair. All the cases were treated by the same surgeon without omental
      interposition. RESULTS: Excellent results were achieved in all 6 cases, with no
      fistula relapse. The urinary infection disappeared in those patients with this
      complication prior to fistula repair. Patient control evaluation was performed 6
      12 months postoperatively and at 4 years. All 6 patients are currently
      urologically asymptomatic and continent. CONCLUSIONS: In our view, vesicovaginal
      fistula repair can be done via the vaginal, abdominal or combined approach. We do
      not believe that one technique is superior over the other. Although the 6 cases
      described herein are not significant statistically, the abdominal-transvecial
      approach has been successful in these 6 cases, despite the difficulty that is
      always encountered in some cases of vesicovaginal fistula, regardless of the
      technique utilized. Omental interposition may be useful in those cases with a
      large fistulous defect. Some advocate fistulectomy in all cases. The time to
      surgical correction following diagnosis was always more than three months. The
      crossed or x-shaped suture achieves minimal superpositioning. Postoperative
      bladder drainage should not lie on the suture of the bladder mucosa to prevent
      decubitus through placement of a cystostomy tube. The foregoing points are
      essential in this procedure.

PMID- 9182491
TI  - [Inferior vena cava obstruction syndrome caused by urinary retention].
AB  - OBJECTIVE: To report an unusual case of inferior vena cava obstruction secondary
      to urinary retention. METHODS/RESULTS: A 72-year-old male patient with a history
      of bilateral inguinal hernia and a recent hip surgery, presented with deep venous
      thrombosis in the left leg. A CT scan disclosed significant thickening of the
      bladder wall and grade III-IV hypertrophy of the prostate. Abdominal ultrasound
      disclosed a cystic mass compressing the vena cava and moderate
      ureterohydronephrosis. Edema spontaneously resolved following insertion of a
      urethral catheter and renal function returned to normal. CONCLUSION: Obstruction
      of the inferior vena cava secondary to an enlarged bladder is rare. To our
      knowledge only two such cases have been reported in the literature. In the case
      described herein, urinary retention may have been exacerbated by prostatic
      hypertrophy, anesthesia and bed confinement due to hip surgery.

PMID- 9182492
TI  - [Triple ureter with inverted ureteral branch in "y" with ectopic ending and
      calculi inside].
AB  - OBJECTIVE: To report an uncommon case of ureteral duplication with a single
      intramural trajectory and a third ureter arising from the medial ureter,
      corresponding to the inferior pyelon, opening at the level of the bladder neck
      and containing a calculus measuring 10 mm along its longest axis, lodged in a
      saccular dilatation. The etiopathogenesis of this rare anomaly is briefly
      reviewed and discussed. METHODS/RESULTS: Diagnosis was established endoscopically
      and pyelographically. Endoscopic resolution was not possible, but stone removal
      was successfully achieved by conventional surgery using the least invasive
      approach possible. The patient is asymptomatic 24 months postoperatively.
      CONCLUSION: Although infrequent, this condition should be suspected in those
      "unclear' cases seen in day-to-day urological practice. Symptoms of the
      associated pathology are more common than those arising from the anomaly.
      Treatment should be specific to each case, as least invasive as possible and
      should aim at symptomatic resolution.

PMID- 9182493
TI  - [Cystic adenoid carcinoma of the prostate. Report of a case].
AB  - OBJECTIVES: To describe a 41-year-old, white, male patient with a previous
      history of rectal pain. He was diagnosed as having a prostatic tumor and was
      treated with antiandrogens and irradiation, which temporarily achieved temporary
      symptomatic relief. When the symptoms reappeared, the patient consulted at our
      hospital. A multinodular tumor was detected in the rectum. Transrectal ultrasound
      guided biopsy disclosed adenoid cystic carcinoma of the prostate or adjacent
      structures. METHODS/RESULTS: The characteristics of the lesion prompted tumor
      excision alone. Since the integrity of the rectal and prostatic urethra could not
      be preserved, a recto-urethral fistula was done, which was subsequently closed
      via the transrectal approach. The clinical characteristics of the tumor and the
      surgical procedure performed required treatment with an antitumoral
      immunomodulator (recombinant a-interferon) for one year. CONCLUSIONS: One and a
      half years postoperatively, no signs of tumor recurrence or distant metastasis
      have been observed. To our knowledge, this is the seventh case reported in the
      world literature and the first in the Spanish literature.

PMID- 9182494
TI  - [Epidemiologic study of renal parenchymal trauma. 22-year experience].
AB  - OBJECTIVE: The results of an epidemiological study on kidney trauma are
      presented. METHODS: We reviewed the epidemiological factors in patients that had
      been admitted to hospital for kidney trauma from 1971 to 1992. RESULTS: Blunt
      trauma (96.3%) was found to be more frequent than penetrating injuries (3.7%).
      Road traffic accidents were the main cause of kidney trauma (50.53%), which was
      more prevalent in the male (male to female ratio 3.75:1) and in the younger
      population (76% were aged 11 to 30 years). Associated extrarenal lesions were
      more commonly found in patients with severe renal trauma. CONCLUSION: Renal
      trauma is relatively uncommon and is more prevalent in males in the second and
      third decades of life. The outcome depends on the degree of severity of the
      injury and the presence of associated extrarenal lesions.

PMID- 9182495
TI  - [Testicular microlithiasis associated with infertility].
AB  - OBJECTIVE: A case of testicular microlithiasis that had been incidentally
      diagnosed by ultrasound in a patient undergoing evaluation for infertility is
      described and the literature briefly reviewed. METHODS: The clinical, laboratory
      (routine blood and urine tests, hormone studies, spermiogram) and testicular
      ultrasound findings in a 28-year-old male who consulted for infertility are
      presented. RESULTS: Serum FSH and LH were raised and testosterone fell within the
      lower ranges. The spermiogram revealed azoospermia. US evaluation showed
      bilateral small hyperechoic foci without posterior acoustic shadowing, dispersed
      within a normal testicular parenchyma. CONCLUSIONS: Testicular microlithiasis is
      a rare entity which is usually discovered incidentally during testicular
      ultrasound evaluation for other conditions such as infertility. The underlying
      condition (calcium in the seminiferous duct lumen) has a specific
      ultrasonographic appearance and further studies are not required to make the
      diagnosis. The patho-genesis and the clinical implications of microlithiasis
      remain unclear, therefore any associated pathology, such as tumor, infertility,
      systemic diseases, or chromosomal disorders, must be ruled out. Regular US follow
      up is advocated.

PMID- 9182496
TI  - [Vesical endometriosis. Report of a case with immunohistochemical study].
AB  - OBJECTIVE: To analyze the hormonal dependence of estrogen and progesterone
      receptors in endometriosis of the bladder. METHODS: A case of endometriosis of
      the bladder that had presented as a tumor in a 30-year-old female is described.
      Immunohistochemical studies were performed using estrogen and progesterone
      antireceptor antibodies. RESULTS: A strong positivity for progesterone in the
      endometriotic stromal cells was demonstrated. A mild positivity for estrogen in
      the glandular epithelial and stromal cells was observed. CONCLUSIONS: The present
      case demonstrates the hormonal dependence of endometriosis of the bladder and
      raises the possibility of utilizing hormone therapy in specific patients.

PMID- 9182497
TI  - [Pseudosarcomatous lesions of the urinary bladder. Report of a case].
AB  - OBJECTIVE: The present study describes a case of pseudosarcomatous lesion of the
      urinary bladder, a rare disease entity that may occasionally be clinically
      mistaken for malignant neoplasms. METHODS/RESULTS: A 79-year-old male with
      hematuria who had previously undergone surgery is described. Cystoscopic
      examination revealed a tumor which was resected by TUR. The histological analysis
      disclosed a benign proliferative mesenchymal lesion comprised of spindle cells.
      CONCLUSIONS: Pseudosarcomatous lesions of the urinary bladder are benign lesions
      of fibroblastic or myofibroblastic origin that are more frequent in young adults
      and prevalent in females. Clinically they present with hematuria and treatment is
      by surgical excision (partial cystectomy or TUR). The prognosis is excellent.

PMID- 9182498
TI  - [Eosinophilic cystitis. Report of 4 cases].
AB  - OBJECTIVE: The etiopathogenesis, clinical features, diagnosis and treatment of
      eosinophilic cystitis are discussed. METHODS/RESULTS: 4 cases of eosinophilic
      cystitis are described. Patient follow-up ranged from 4 to 6.5 years. All
      patients are currently asymptomatic. Except for one patient who required
      hospitalization on several occasions due to hematuria secondary to cystitis, the
      remaining patients had an exceptional episode. CONCLUSIONS: Eosinophilic cystitis
      is an inflammatory condition whose etiopathogenesis remains to be elucidated. Its
      natural history is usually unpredictable and treatment is rarely effective.
      Eosinophilic cystitis has been associated with other allergic disorders and has
      been reported in patients with BPH and carcinoma of the bladder.

PMID- 9182499
TI  - [Ureteral stenosis secondary to Churg-Strauss allergic granulomatous vasculitis].
AB  - OBJECTIVE: Ureteral stenosis secondary to vasculitis is a rare disease. The
      etiology and treatment of this unusual cause of ureteral obstruction are
      discussed. METHODS/RESULTS: We report a case of ureteral obstruction secondary to
      Churg-Strauss vasculitis in a 45-year-old man. The patient was treated with
      prednisone and cyclophosphamide. Subsequently ureteral resection and
      reanastomosis were performed. CONCLUSIONS: Vasculitis of the ureter should be
      considered in patients with connective tissue disorders who present with ureteral
      dilatation. In some cases ureteral stenosis may require surgery in combination
      with steroid and/or immunosuppressive therapy.

PMID- 9182500
TI  - [Calcium ions in the life cycle of Streptomyces albogriseolus 444].
AB  - The influence of Ca2+ on the growth, antibiotic production and differentiation of
      Streptomyces albogriseolus 444 was studied. Consumption of the calcium ions by
      the strain was followed up. It was shown that Ca2+ changed the dynamics of the
      biomass accumulation and had no significant effect on the antibiotic production.
      Calcium present in the medium was assimilated more intensively during the first
      24 hours of the strain growth. The own antibiotic nigericin exogenously added to
      the medium increased the calcium assimilation. In the presence of Ca2+ the
      nigericin stimulation of the strain differentiation was higher.

PMID- 9182501
TI  - [Cytotoxic properties of the complex of the antineoplastic antibiotic bleomycetin
      and Bacillus intermedius ribonuclease].
AB  - It was shown possible to change the cytotoxic properties of the antitumor
      antibiotic bleomycetin by its binding to Bacillus intermedius RNAse. The
      complexing lowered the antibiotic effect on DNA in the cells of the human amnion.
      At the same time the experiments with human red blood cells indicated that RNAse
      of B. intermedius in complex with bleomycetin-Fe(II) increased the antibiotic
      capacity for the cell membrane break down.

PMID- 9182502
TI  - [Effect of medium temperature and pH on the sensitivity of pathogenic
      pseudomonads to chemotherapeutic agents].
AB  - Antibiotic susceptibility of four Pseudomonas species i.e. P.aeruginosa,
      P.cepacia, P.mallei and P.pseudomallei was studied under conditions of different
      temperature and pH of the medium (within the physiologically possible
      deviations). It was shown that along with the general tendencies (lowered MICs at
      the medium alkalization) there were obvious species differences in the effect of
      the physicochemical factors on the Pseudomonas antibiotic resistance. The results
      of the study may to a certain extent serve as an explanation of the lack of
      coincidence of the chemotherapy efficacy with the data on the drug in vitro
      estimation.

PMID- 9182503
TI  - [Toxic properties of recombinant tumor necrosis factor].
AB  - Toxic properties of recombinant human tumor necrosis factor (TNF-beta) were
      studied on noninbred albino mice. In the maximum tolerable doses the preparation
      induced a decrease in the body weight and temperature of the animals as well as
      development of glyco- and leukopenic reactions and damage of the internal organ
      structures. The preparation effects were observed early after the exposure and
      were mainly reversible. The most TNF-beta sensitive organs were the liver, lungs,
      adrenal gland, thymus and spleen. The major link in the pathological process
      development under the effect of the TNF-beta toxic doses was likely increased
      intravascular blood coagulability evident from a marked procoagulant activity of
      the preparation.

PMID- 9182504
TI  - [Aspects of solution of the postoperative infection problem in heart surgery].
AB  - The study of the incidence and etiological pattern of infectious complications
      included 376 patients operated for acquired valvular disease. 40,280
      bacteriological tests of the materials from the patients obtained during the
      operations and during the postoperative period as well as 30,113 sanitary
      bacteriological tests of the specimens from the cardiological operation unit were
      conducted. The possible use of the results of bacteriological monitoring for
      prediction of septic complications and optimization of antibiotic prophylaxis and
      therapy as well as for development and operation of a system of sanitary and
      hygienic measures for infection prevention was shown and statistically confirmed.

PMID- 9182505
TI  - [Effect of Ca2+ ions on biosynthesis and component composition of tylosin in
      Streptomyces fradiae].
AB  - The influence of Ca2+ ions on biosynthesis of tylosin complex by Streptomyces
      fradiae in an enriched medium under submerged conditions was studied. It was
      shown that Ca2+ (at the concentration of 20 to 30 mM CaCl2) stimulated the
      tylosin biosynthesis by eliminating the limit of incorporation of the precursors
      such as macrocin and desmycosin to the process and by inhibiting catabolism of
      tylosin to relomycin. No potentiation of the Ca2+ influence by effectors of cAMP
      metabolism i.e. sodium fluoride and papaverin was observed.

PMID- 9182506
TI  - [Amphotericin B: properties, chemical structure, screening of derivatives].

PMID- 9182507
TI  - [Metabolites produced by Streptomyces kanamyceticus mutants with impaired
      biosynthesis of kanamycin].
AB  - Metabolites produced by Streptomyces kanamyceticus mutants with impaired
      kanamycin biosynthesis (kan mutants) were investigated by thin layer
      chromatography. With spectrophotometric scanning of the chromatograms the
      quantitative content of kanamycin A and 2-desoxystreptamine (2-DOS) in the
      culture fluid was determined. Five groups of the S.kanamyceticus mutants with
      impaired kanamycin biosynthesis at various stages were identified: kanA produced
      no D-glucosamine, kanB and kanC produced no 2-DOS, kanD was not able to transfer
      2-DOS to the metabolites with the antibiotic activity, kanG synthesized no
      kanosamine.

PMID- 9182508
TI  - Applied toxicology: approaches through basic science. Proceedings of the 1996
      EUROTOX Congress Meeting. Alicante, Spain, September 22-25, 1996.

PMID- 9182509
TI  - Magnetic resonance imaging of traumatic transection of the optic chiasm.

PMID- 9182510
TI  - [Verotoxin-producing E. coli (VTEC) in feces from cattle slaughtered in Germany].
AB  - In man, EHEC infections may result in severe disease. Cattle and foods derived
      from this animal species are considered as a source of infection. The presence of
      VTEC being potential EHEC was studied. For analysis, feces samples were examined
      which had been taken from 204 heads of cattle slaughtered in various regions of
      Germany. VTEC could be isolated from 97 animals (47.6%). This indicates a
      presence of VTEC in slaughtered cattle being 5 times higher than known for
      Germany so far. The aeaA gene could be demonstrated in a mere 23 out of 667 VTEC
      isolates. The CVD 419 sequence was present in 55.3% of the VTEC isolates. Ehly
      was found in 61% of them. Consequently, both markers were unsuitable for the
      detection of VTEC in faeces samples from cattle and in foods with faecal
      contamination. The VTEC isolates belonged to 54 different serotypes of E. coli,
      VTEC 0157 have not been found so far. Some of the VTEC serovars found in this
      study have already been described as associated with human disease following EHEC
      infection. The presently available laboratory methods do not permit to exclude a
      risk for humans from bovine VTEC reliably. For this reason, bovine VTEC should be
      further on considered as potential EHEC and an infection of humans by such agents
      be avoided.

PMID- 9182511
TI  - [Allergenicity and specific protein profiles of mange mites Chorioptes bovis,
      Psoroptes ovis (Acari: Psoroptidae), Saroptes suis and Notoedres cati (Acari:
      Sarcoptidae) using SDS-PAGE and immunoblotting].
AB  - A main point of immunoparasitological research in regard to pest arthropod
      infestation is biochemical and immunological characterization of antigens.
      Precondition of own examinations to the specific protein pattern of mange mites
      were in quality and amount sufficient antigen preparations in mite extract
      solutions. For mite separation and antigen refinement field strains of Chorioptes
      bovis, Psoroptes ovis, Sarcoptes suis and Notoedres cati from definitive host
      animals cattle, sheep, pig and cat have been used. Parasites were isolated in a
      migration procedure. After having applicated subepidermally a low dose of mite
      extract solutions in sensitized animals allergic skin changes (Immediate reaction
      type 1) became apparent. SDS-PAGE exhibited specific protein patterns of 4
      pathogen mite species. For Chorioptes bovis 16, Psoroptes ovis 15, Sarcoptes suis
      27, and Notoedres cati 36 fractions have been detected. Proteins are antigens or
      allergen structures to be found in saliva, faecal output or moulting products of
      developmental stages and other metabolites of the parasites. Protein components
      were transferred onto nitrocellulosis. Immunoblotting made fractions with antigen
      activity visible.

PMID- 9182512
TI  - [Nursing and suckling behavior and mother-child contacts in domestic rabbits].
AB  - Investigations with 34 litters of rabbits breed White New Zealands by the help of
      infrared videotechnique over 242 day-night-periods (24 hr per period) showed a
      frequency of 15.1 mother-child-contacts on average of 24 hr (Min: 6, Max: 48
      contacts a day). In 38% of all 24-hr-cycles observed one suckling event was found
      and in 56.6% of all cases two up to five suckling periods were seen (5.4% of all
      24-hr-periods were without suckling). Mean suckling frequency per 24 hr was 1.83
      with maximum in second suckling week (2.31). Highly significant positive
      coefficients of correlation (r = 0.33 up to r = 0.89) were found between birth
      weight, daily gain, milk intake and weaning weight. Mother-child-relations in
      rabbits (breed White New Zealands) are more intensive as thought up to now so
      that the separation of mother from her litter represents an intervention into
      species-specific behaviour.

PMID- 9182513
TI  - [Detection of dermonecrotic toxin genes in Pasteurella multocida strains using
      the polymerase chain reaction (PCR)].
AB  - A PCR method was developed which allows to distinguish between Pasteurella
      multocida strains carrying or lacking the dermonecrotic toxin gene. Specific
      primers were used to amplify a 1501-bp DNA fragment from the genomic
      dermonecrotic toxin gene region. Isolated DNA, broth cultures and swabs were used
      as samples. Detection of the toxin gene directly from swab samples accelerates
      considerably the diagnosis since cultivation steps can be omitted. The results of
      PCR corresponded to findings obtained by ELISA.

PMID- 9182514
TI  - [Sex steroid profiles and ovarian activities of the female panda Yan Yan in the
      Berlin Zoo].
AB  - The nine years old giant panda YAN YAN was received in April 1995 on loan for 5
      years to the Berlin Zoo. Urine samples were collected daily or every second day
      from April 1995 to June 1996 in order to follow up sex hormone secretions and
      ovarian activities. Conjugated steroids were hydrolysed, extracted and measured
      with two enzyme immuno assays (EIA) being specific for either total oestrogenes
      or pregnandiol. The evaluation of the hormone secretion pattern yielded the
      following results: There is a significant synchronous cross correlation between
      estrogen and progestin metabolites secretion indicating its simultaneous
      synthesis. In addition, we found a regular increase and decrease of both hormones
      with a 13 days interval. This secretory pattern indicates repeating development
      and atresia of follicle cohorts with a cycle length of about 13 days. Only a
      single period of slightly elevated oestrogen synthesis was monitored in Feb. 96
      without any signs of oestrus. Obviously the stimulation of ovarian function was
      insufficient for complete ovulation and corpus luteum formation.

PMID- 9182515
TI  - [Occurrence of helminths in slaughtered sheep in Upper Bavaria. 2. Relationship
      between fecal egg count and worm burden].
AB  - The relationship between the faecal egg count and the worm burden of the
      gastrointestinal tract of sheep was examined. Close relationships were found in
      strongyles, Trichostrongylidae (other than Nematodirus spp.), Nematodirus spp.,
      Strongyloides papillosus, Chabertiidae and Trichuris spp.. Due to high percentage
      of false negative diagnosis from faecal examination, this relationship was in
      Nematodirus spp. and Trichuris spp. not as close as in the other nematodes.
      However, the results support the high diagnostic value of quantitative faecal
      examinations in sheep.

PMID- 9182516
TI  - What is the time scale of magnetic field interaction in biological systems?
AB  - An experimental test constraining the intrinsic time scale of a primary physical
      mechanism that detects extremely-low-frequency (ELF) magnetic fields in
      biological systems is proposed. The suggested test postulates that a transductive
      mechanism operating on time scales much shorter than the period of an applied
      magnetic field cannot obtain any information about the exposure conditions other
      than the absolute magnitude of the field. By generating field exposure that
      differ in their vector properties but are equivalent in their time-varying
      absolute amplitude, it is possible to differentiate between two broad classes of
      mechanisms: 1) those with intrinsic time scales comparable with or longer than
      those of the external influence, and 2) those that are much faster than the
      period of the applied field. The hypothesis assumes an experimental model proven
      to respond to magnetic fields and sensitive to a change of about a factor of two
      in one of the field parameters (AC, DC amplitude or frequency). The case of
      general linearly polarized fields is discussed, and an analytical solution for
      the case of perpendicular AC/DC fields is given.

PMID- 9182518
TI  - A thematic series on phospholipases.

PMID- 9182519
TI  - Regulation of phosphoinositide-specific phospholipase C isozymes.

PMID- 9182520
TI  - Identification of the MDM2 oncoprotein as a substrate for CPP32-like apoptotic
      proteases.
AB  - Programmed cell death is mediated by members of the interleukin 1-beta convertase
      family of proteases, which are activated in response to diverse cell death
      stimuli. However, the key substrates of these proteases that are responsible for
      apoptotic cell death have not been identified. Here we report that the MDM2
      oncoprotein is cleaved by members of the CPP32 subfamily of interleukin 1-beta
      convertase proteases both in vitro and in vivo, resulting in the disappearance of
      MDM2 from apoptotic cells. Because MDM2 functions as a negative regulator of the
      p53 tumor suppressor and because p53 induces apoptosis in response to a variety
      of stimuli, this cleavage of MDM2 by CPP32-like proteases may result in
      deregulation of p53 and contribute directly to the process of apoptotic cell
      death.

PMID- 9182521
TI  - Mutation of Cys672 allows recombinant expression of activatible macrophage
      stimulating protein.
AB  - We readily produced recombinant pro-macrophage stimulating protein in a mammalian
      expression system, but it was only weakly active after proteolytic activation.
      Active macrophage stimulating protein is a disulfide-bonded heterodimer, but in
      our hands, the subunits of recombinant macrophage stimulating protein were mostly
      not disulfide bonded. Molecular modeling of the serine proteinase domain of
      macrophage stimulating protein based on homology to human trypsin suggested that
      macrophage stimulating protein, but not plasminogen or hepatocyte growth factor,
      has a Cys residue (672) in close proximity to the Cys residue (578) that forms
      the intersubunit disulfide link with the other subunit. We hypothesized that
      Cys672 might interfere with intersubunit disulfide formation by forming an
      intrasubunit disulfide with Cys578 and therefore mutated Cys672 to Ala. After
      kallikrein activation, the subunits of Cys672 --> Ala macrophage stimulating
      protein were fully disulfide linked, and the mutant macrophage stimulating
      protein had 10-20-fold higher specific activity than the wild type recombinant
      macrophage stimulating protein.

PMID- 9182522
TI  - Corticotropin-releasing factor and adrenocorticotrophic hormone as potential
      central mediators of OB effects.
AB  - OB (leptin) has been identified as a factor that suppresses appetite and
      stimulates metabolism. Attention has focused on the hypothalamus as its potential
      site of action, but OB could also act on other brain regions. In addition, the
      paradox of high OB levels in obese humans remains unresolved. Here we show in
      mice that both the long and short form of the OB receptor are expressed not only
      in the hypothalamus but also in the amygdala and pituitary. Recombinant murine OB
      elicited the release of corticotropin-releasing factor from superfused brain
      slice preparations containing hypothalamus or amygdala. Because corticotropin
      releasing factor inhibits appetite and stimulates metabolism, it may be a key
      mediator of central OB effects. Recombinant OB also induced pituitary release of
      adrenocorticotrophic hormone. Because adrenocorticotrophic hormone-induced
      elevation of plasma glucocorticoid levels can inhibit corticotropin-releasing
      factor release via negative feedback, the OB effects on pituitary
      adrenocorticotrophic hormone release may be pertinent to human obesity, which
      combines increased plasma glucocorticoid levels with elevated levels of OB. An
      imbalance between the effects of OB on corticotropin-releasing factor release
      from the hypothalamus and on adrenocorticotrophic hormone release from the
      pituitary could contribute to obesity.

PMID- 9182523
TI  - Phospholamban inhibitory function is activated by depolymerization.
AB  - Phospholamban (PLN), a homopentameric, integral membrane protein, reversibly
      inhibits cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity through
      intramembrane interactions. Here, alanine-scanning mutagenesis of the PLN
      transmembrane sequence was used to identify two functional domains on opposite
      faces of the transmembrane helix. Mutations in one face diminish inhibitory
      interactions with transmembrane sequences of SERCA2a, but have relatively little
      effect on the pentameric state, while mutations in the other face activate
      inhibitory interactions and enhance monomer formation. Double mutants are
      monomeric, but loss of inhibitory function is dominant over activation of
      inhibitory function. These observations support the proposal that the SERCA2a
      interaction site lies on the helical face which is not involved in pentamer
      formation. Four highly inhibitory mutants are effectively devoid of pentamer,
      suggesting that pentameric PLN represents a less active or inactive reservoir
      that dissociates to provide inhibitory monomeric PLN subunits. A model is
      presented in which the degree of PLN inhibition of SERCA2a activity is ultimately
      determined by the concentration of the inhibited PLN monomer.SERCA2a
      heterodimeric complex. The concentration of this inhibited complex is determined
      by the dissociation constant for the PLN pentamer (which is mutation-sensitive)
      and by the dissociation constant for the PLN/SERCA2a heterodimer (which is likely
      to be mutation-sensitive).

PMID- 9182524
TI  - Interactions between the F1 and F0 parts in the Escherichia coli ATP synthase.
      Associations involving the loop region of C subunits.
AB  - The N-ethylmaleimide reactivity of c subunits in Escherichia coli F1F0 ATP
      synthase (ECF1F0) isolated from five mutants, each with a cysteine at a different
      position in the polar loop region (positions 39, 40, 42, 43, and 44), has been
      investigated. The maleimide was found to react with Cys placed at positions 42,
      43, and 44 but not at 39 or 40. All copies of the c subunit reacted similarly
      when the Cys was at position 43 or 44. In contrast, the Cys in the mutant cQ42C
      reacted as two classes, with 60% reacting relatively rapidly and 40% reacting at
      a rate 40-fold slower. After removing F1, all copies of the c subunit in this
      mutant reacted equally fast. Therefore, the slow class in the cQ42C mutant
      represents c subunits shielded by, and probably involved directly in, the
      interaction of the F0 with gamma and epsilon subunits of the F1 part. Based on
      the estimated stoichiometry of c subunits in the ECF1F0 complex, 4 or 5 c
      subunits are involved in this F1 interaction. N-Ethylmaleimide modification of
      all of the c subunits reduced ATPase activity by only 30% in ECF1F0 from mutant
      cQ42C. Modification of the more rapidly reacting class had little effect on ATP
      hydrolysis-driven proton translocation, and did not alter the DCCD inhibition of
      ATPase activity. However, as those c subunits involved in the F1 interaction
      became modified, DCCD inhibition was progressively lost, as was coupling between
      ATP hydrolysis and proton translocation.

PMID- 9182525
TI  - Activation of the avian erythrocyte Na-K-Cl cotransport protein by cell
      shrinkage, cAMP, fluoride, and calyculin-A involves phosphorylation at common
      sites.
AB  - Na-K-Cl cotransport activity in duck erythrocytes increases approximately 10-fold
      in response to osmotic cell shrinkage, norepinephrine, fluoride, or calyculin-A
      (an inhibitor of type-1 and -2a phosphatases). To assess whether all four stimuli
      promote phosphorylation of the cotransport protein and whether this
      phosphorylation is catalyzed by the same kinase, the cotransporter was isolated
      from erythrocytes by immunoprecipitation and its pattern of phosphorylation was
      evaluated. Each stimulus evoked proportionate increases in cotransporter activity
      and phosphorylation. No two stimuli in combination evoked greater activation and
      phosphorylation than did the more potent of the two stimuli acting alone.
      Phosphoamino acid analysis of the cotransport protein indicated that
      phosphorylation occurs at serine and threonine residues. Phosphopeptide mapping
      revealed a distinctive pattern of 8 major tryptic phosphopeptides, none of which
      were significantly phosphorylated in the unstimulated state. Maps of
      cotransporters activated by the four different stimuli were indistinguishable.
      Measurements of phosphorylation stoichiometry indicated that each cotransporter
      acquires approximately 5 phosphates on going from an inactive state in swollen
      cells to an active state in shrunken cells. Staurosporine, a kinase inhibitor
      with broad selectivity, inhibited each stimulus equipotently (IC50 approximately
      0.7 microM). Staurosporine promptly reversed cotransporter activity and
      phosphorylation when added to shrinkage-stimulated but not to calyculin
      stimulated cells, indicating that it enters the cell rapidly and blocks
      phosphorylation. These results suggest that cell shrinkage, cAMP, fluoride, and
      calyculin-A promote the phosphorylation of the Na-K-Cl cotransport protein at a
      similar constellation of serine and threonine residues. It is proposed that all
      modes of stimulation ultimately involve the same protein kinase.

PMID- 9182526
TI  - Beta3A-adaptin, a subunit of the adaptor-like complex AP-3.
AB  - Recent studies have described a widely expressed adaptor-like complex, named AP
      3, which is likely involved in protein sorting in exocytic/endocytic pathways.
      The AP-3 complex is composed of four distinct subunits. Here, we report the
      identification of one of the subunits of this complex, which we call beta3A
      adaptin. The predicted amino acid sequence of beta3A-adaptin reveals that the
      protein is closely related to the neuron-specific protein beta-NAP (61% overall
      identity) and more distantly related to the beta1- and beta2-adaptin subunits of
      the clathrin-associated adaptor complexes AP-1 and AP-2, respectively. Sequence
      comparisons also suggest that beta3A-adaptin has a domain organization similar to
      beta-NAP and to beta1- and beta2-adaptins. beta3A-adaptin is expressed in all
      tissues and cells examined. Co-purification and co-precipitation analyses
      demonstrate that beta3A-adaptin corresponds to the approximately 140-kDa subunit
      of the ubiquitous AP-3 complex, the other subunits being delta-adaptin, p47A (now
      called mu3A) and sigma3 (A or B). beta3A-adaptin is phosphorylated on serine
      residues in vivo while the other subunits of the complex are not detectably
      phosphorylated. beta3A-adaptin is not present in significant amounts in clathrin
      coated vesicles. The characteristics of beta3A-adaptin reported here lend support
      to the idea that AP-3 is a structural and functional homolog of the clathrin
      associated adaptors AP-1 and AP-2.

PMID- 9182527
TI  - Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of
      mammalian HECT family ubiquitin protein ligases.
AB  - In most instances, the transfer of ubiquitin to target proteins is catalyzed by
      the action of ubiquitin protein ligases (E3s). Full-length cDNAs encoding murine
      E6-associated protein (mE6-AP) as well as Nedd-4, a protein that is homologous to
      E6-AP in its C terminus, were cloned. Nedd-4 and mouse E6-AP are both
      enzymatically active E3s and function with members of the UbcH5 family of E2s.
      Mouse E6-AP, like its human counterpart, ubiquitinates p53 in the presence of
      human papilloma virus E6 protein, while Nedd-4 does not. Consistent with its role
      in p53 ubiquitination, mE6-AP was found both in the nucleus and cytosol, while
      Nedd-4 was found only in the cytosol. Binding studies implicate a 150-amino acid
      region that is 40% identical between mE6-AP and Nedd-4 as a binding site for the
      C-terminal portion of an E2 enzyme (UbcH5B). Nedd-4 was determined to have a
      second nonoverlapping E2 binding site that recognizes the first 67 amino acids of
      UbcH5B but not the more C-terminal portion of this E2. These findings provide the
      first demonstration of physical interactions between mammalian E2s and E3s and
      establish that these interactions occur independently of ubiquitin and an intact
      E3 catalytic domain. Furthermore, the presence of two E2 binding sites within
      Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes
      associated with E3s.

PMID- 9182528
TI  - Characterization of the heparin binding properties of annexin II tetramer.
AB  - In this report, we have characterized the interaction of heparin with the Ca2+-
      and phospholipid-binding protein annexin II tetramer (AIIt). Analysis of the
      circular dichroism spectra demonstrated that the Ca2+-dependent binding of AIIt
      to heparin caused a large decrease in the alpha-helical content of AIIt from
      approximately 44 to 31%, a small decrease in the beta-sheet content from
      approximately 27 to 24%, and an increase in the unordered structure from 20 to
      29%. The binding of heparin also decreased the Ca2+ concentration required for a
      half-maximal conformational change in AIIt from 360 to 84 microM. AIIt bound to
      heparin with an apparent Kd of 32 +/- 6 nM (mean +/- S.D., n = 3) and a
      stoichiometry of 11 +/- 0.9 mol of AIIt/mol of heparin (mean +/- S.D., n = 3).
      The binding of heparin to AIIt was specific as other sulfated polysaccharides did
      not elicit a conformational change in AIIt. A region of the p36 subunit of AIIt
      (Phe306-Ser313) was found to contain a Cardin-Weintraub consensus sequence for
      glycosaminoglycan recognition. A peptide to this region underwent a
      conformational change upon heparin binding. Other annexins contained the Cardin
      Weintraub consensus sequence, but did not undergo a substantial conformational
      change upon heparin binding.

PMID- 9182529
TI  - A new member of the amphiphysin family connecting endocytosis and signal
      transduction pathways.
AB  - Src homology 3 (SH3) domains are conserved modules which participate in protein
      interaction by recognizing proline-rich motifs on target molecules. To identify
      new SH3-containing proteins, we performed a two-hybrid screen with a proline-rich
      region of human SOS-1. One of the specific SOS-1 interacting clones that were
      isolated from a mouse brain cDNA library defines a new protein that was named
      amphiphysin 2 because of its homology to the previously reported amphiphysin.
      Amphiphysin 2 is expressed in a number of mouse tissues through multiple RNA
      transcripts. Here, we report the amino acid sequence of a brain form of
      amphiphysin 2 (BRAMP2) encoded by a 2. 5-kilobase mRNA. BRAMP2 associates in
      vitro with elements of the endocytosis machinery such as alpha-adaptin and
      dynamin. On a biosensor surface, the BRAMP2/dynamin interaction appeared to be
      direct and partly dependent on a proline-rich sequence of dynamin. Association
      with dynamin was also observed in PC12 cells after cell stimulation with nerve
      growth factor, suggesting that amphiphysin 2 may be connected to receptor
      dependent signaling pathways. This hypothesis is strengthened by the ability of
      BRAMP2 to interact with the p21(ras) exchange factor SOS, in vitro, as a possible
      point of interconnection between the endocytic and signaling pathways.

PMID- 9182530
TI  - Comparative enzymatic properties of GapB-encoded erythrose-4-phosphate
      dehydrogenase of Escherichia coli and phosphorylating glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - GapB-encoded protein of Escherichia coli and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) share more than 40% amino acid identity. Most of the amino
      acids involved in the binding of cofactor and substrates to GAPDH are conserved
      in GapB-encoded protein. This enzyme shows an efficient non-phosphorylating
      erythrose-4-phosphate dehydrogenase activity (Zhao, G., Pease, A. J., Bharani,
      N., and Winkler, M. E. (1995) J. Bacteriol. 177, 2804-2812) but a low
      phosphorylating glyceraldehyde-3-phosphate dehydrogenase activity, whereas GAPDH
      shows a high efficient phosphorylating glyceraldehyde-3-phosphate dehydrogenase
      activity and a low phosphorylating erythrose-4-phosphate dehydrogenase activity.
      To identify the structural factors responsible for these differences, comparative
      kinetic and binding studies have been carried out on both GapB-encoded protein of
      Escherichia coli and GAPDH of Bacillus stearothermophilus. The KD constant of
      GapB-encoded protein for NAD is 800-fold higher than that of GAPDH. The chemical
      mechanism of erythrose 4-phosphate oxidation by GapB-encoded protein is shown to
      proceed through a two-step mechanism involving covalent intermediates with Cys
      149, with rates associated to the acylation and deacylation processes of 280 s-1
      and 20 s-1, respectively. No isotopic solvent effect is observed suggesting that
      the rate-limiting step is not hydrolysis. The rate of oxidation of glyceraldehyde
      3-phosphate is 0.12 s-1 and is hydride transfer limiting, at least 2000-fold less
      efficient compared with that of erythrose 4-phosphate. Thus, it can be concluded
      that it is only the structure of the substrates that prevails in forming a
      ternary complex enzyme-NAD-thiohemiacetal productive (or not) for hydride
      transfer in the acylation step. This conclusion is reinforced by the fact that
      the rate of oxidation for erythrose 4-phosphate by GAPDH is 0.1 s-1 and is
      limited by the acylation step, whereas glyceraldehyde 3-phosphate acylation is
      efficient and is not rate-determining (>/=800 s-1). Substituting Asn for His-176
      on GapB-encoded protein, a residue postulated to facilitate hydride transfer as a
      base catalyst, decreases 40-fold the kcat of glyceraldehyde 3-phosphate
      oxidation. This suggests that the non-efficient positioning of the C-1 atom of
      glyceraldehyde 3-phosphate relative to the pyridinium of the cofactor within the
      ternary complex is responsible for the low catalytic efficiency. No
      phosphorylating activity on erythrose 4-phosphate with GapB-encoded protein is
      observed although the Pi site is operative as proven by the oxidative
      phosphorylation of glyceraldehyde 3-phosphate. Thus the binding of inorganic
      phosphate to the Pi site likely is not productive for attacking efficiently the
      thioacyl intermediate formed with erythrose 4-phosphate, whereas a water molecule
      is an efficient nucleophile for the hydrolysis of the thioacyl intermediate.
      Compared with glyceraldehyde-3-phosphate dehydrogenase activity, this corresponds
      to an activation of the deacylation step by >/=4.5 kcal.mol-1. Altogether these
      results suggest subtle structural differences between the active sites of GAPDH
      and GapB-encoded protein that could be revealed and/or modulated by the structure
      of the substrate bound. This also indicates that a protein engineering approach
      could be used to convert a phosphorylating aldehyde dehydrogenase into an
      efficient non-phosphorylating one and vice versa.

PMID- 9182531
TI  - Regulation of platelet plasma membrane Ca2+-ATPase by cAMP-dependent and tyrosine
      phosphorylation.
AB  - As a consequence of its central role in the regulation of calcium metabolism in
      the platelet, the plasma membrane Ca2+-ATPase (PMCA) was assessed for cAMP
      dependent and tyrosine phosphorylation. Addition of forskolin or prostaglandin
      E1, agents known to elevate platelet cAMP and calcium efflux, to platelets pre
      labeled with [32P]PO4 resulted in the direct phosphorylation of platelet PMCA.
      Similarly, addition of the catalytic subunit of protein kinase A to platelet
      plasma membranes resulted in a 1.4-fold stimulation of activity. Thus, the
      previously reported inhibition of platelet activation by elevated intracellular
      cAMP may be accomplished in part by stimulation of PMCA, likely resulting in a
      decrease in intracellular calcium. Treatment with thrombin evoked tyrosine
      phosphorylation of platelet PMCA, while PMCA from resting platelets exhibited
      little tyrosine phosphorylation. Phosphorylation of platelet plasma membranes by
      pp60(src) resulted in 75% inhibition of PMCA activity within 15 min. Similarly,
      membranes isolated from thrombin-treated platelets exhibited 40% lower PMCA
      activity than those from resting platelets. Phosphorylation of erythrocyte ghosts
      and purified PMCA by pp60(src) also resulted in up to 75% inhibition of Ca2+
      ATPase activity, and inhibition was correlated with tyrosine phosphorylation.
      Sequencing of a peptide obtained after 32P labeling of purified erythrocyte PMCA
      in vitro showed that tyrosine 1176 of PMCA4b is phosphorylated by pp60(src).
      These results indicate that tyrosine phosphorylation of platelet PMCA may serve
      as positive feedback to inhibit PMCA and increase intracellular calcium during
      platelet activation.

PMID- 9182532
TI  - A mouse histone H1 variant, H1b, binds preferentially to a regulatory sequence
      within a mouse H3.2 replication-dependent histone gene.
AB  - H1 histones, found in all multicellular eukaryotes, associate with linker DNA
      between adjacent nucleosomes, presumably to keep the chromatin in a compact,
      helical state. The identification of multiple histone H1 subtypes in vertebrates
      suggests these proteins have specialized roles in chromatin organization and thus
      influence the regulation of gene expression in the multicellular organism. The
      mechanism by which the association of H1 with nucleosomal DNA is regulated is not
      completely understood, but affinity for different DNA sequences may play a role.
      Here we report that a specific H1 subtype in the mouse, namely H1b, selectively
      binds to a regulatory element within the protein-encoding sequence of a
      replication-dependent mouse H3.2 gene. We have previously shown that this coding
      region element, Omega, is the target of very specific interactions in vitro with
      another nuclear factor called the Omega factor. This element is required for
      normal gene expression in stably transfected rodent cells. The mouse H1b protein
      interacts poorly (100-fold lower affinity) with the comparable "Omega" sequence
      of a replication-independent mouse H3.3 gene. This H3.3 sequence differs at only
      4 out of 22 nucleotide positions from the H3.2 sequence. Our findings raise the
      possibility that this H1b protein plays a specific role in regulation of
      expression of the replication-dependent histone gene family.

PMID- 9182533
TI  - A single mutation in the heme 4 environment of Desulfovibrio desulfuricans Norway
      cytochrome c3 (Mr 26,000) greatly affects the molecule reactivity.
AB  - The gene encoding Desulfovibrio desulfuricans Norway cytochrome c3 (Mr 26,000), a
      dimeric octaheme cytochrome belonging to the polyheme cytochrome c3 superfamily,
      has been cloned and successfully expressed in another sulfate reducing bacteria,
      D. desulfuricans G201. The gene, named cycD, is monocistronic and encodes a
      cytochrome precursor of 135 amino acids with an extension at the NH2 terminus of
      24 amino acids. This extension acts as a signal sequence which allows export
      across the cytoplasmic membrane into the periplasmic space. Tyrosine 73, which is
      in a close contact with the histidine sixth axial ligand to the heme 4 iron atom,
      has been replaced by a glutamate residue using site-directed mutagenesis. The
      cytochrome mutant when expressed in D. desulfuricans G201, is correctly folded
      and matured. A global increase of the oxidoreduction potentials of about 50 mV is
      measured for the Y73E cytochrome. The mutation also has a strong influence on the
      interaction of the cytochrome with its redox partner, the hydrogenase. This
      suggests, like the tetraheme cytochrome c3 (Mr 13, 000), heme 4 is the
      interactive heme in the cytochrome-hydrogenase complex and that alteration of the
      heme 4 environment can greatly affect the electron transfer reaction with its
      redox partner.

PMID- 9182535
TI  - Ortho-substituted polychlorinated biphenyls alter microsomal calcium transport by
      direct interaction with ryanodine receptors of mammalian brain.
AB  - A stringent structure-activity relationship among polychlorinated biphenyls
      (PCBs) possessing two or more ortho-chlorine substituents is observed for
      activation of ryanodine receptors in mammalian brain, revealing an
      arylhydrocarbon receptor-independent mechanism through which non-coplanar PCBs
      disrupt neuronal Ca2+ signaling. Of the congeners assayed, non-coplanar PCB 95
      exhibits the highest potency (EC50 = 12-24 microM) toward activating high
      affinity [3H]ryanodine-binding in rat hippocampus, cerebellum, and cerebral
      cortex. Coplanar PCB 66 and PCB 126 have no ryanodine receptor activity in all
      brain regions examined. PCB 95 enhances [3H]ryanodine-binding affinity and
      capacity by significantly altering modulation by Ca2+ and Mg2+, thereby
      stabilizing a high affinity conformation of the ryanodine receptor. Ca2+
      transport measurements using cortical microsomes reveal that PCB 95 discriminates
      between inositol 1,4,5-trisphosphate- and ryanodine-sensitive stores. PCB 95
      selectively mobilizes Ca2+ from ryanodine-sensitive stores in a dose-dependent
      manner (EC50 = 3.5 microM) and is completely inhibited by ryanodine receptor
      blockers, whereas coplanar PCBs are inactive. These data demonstrate that ortho
      substituted PCBs disrupt Ca2+ transport in central neurons by direct interaction
      with ryanodine receptors, showing high selectivity and specificity. Alteration of
      Ca2+ signaling mediated by ryanodine receptors in specific regions of the central
      nervous system may account, at least in part, for the significant impact of these
      agents toward neurodevelopment and neuroplasticity in mammals.

PMID- 9182534
TI  - Influence of subunit combinations on signaling by receptors for oncostatin M,
      leukemia inhibitory factor, and interleukin-6.
AB  - Oncostatin M (OSM), leukemia inhibitory factor (LIF), and interleukin-6 (IL-6)
      induce expression of a similar set of acute phase plasma protein genes in hepatic
      cells. The redundant action of these cytokines has been ascribed to the
      involvement of the common signal-transducing receptor subunit, gp130, in
      combination with cytokine-specific, ligand-binding subunits. To define the
      specificity of the signal transduction by the LIF/OSM receptor (a heterodimer of
      gp130 and LIF receptor (LIFR)) and the OSM-specific receptor (a heterodimer of
      gp130 and OSM receptor (OSMR)), we reconstituted the receptor function by
      transfection into receptor-negative Hep3B hepatoma cells. Both receptors activate
      DNA binding activity of STAT1, -3, and -5B and induce gene transcription through
      IL-6-responsive elements. The signaling-competent cytoplasmic domain regions of
      OSMR and LIFR were defined by the analysis of progressive carboxyl-terminal
      deletion constructs. The 36 residue carboxyl-terminal region containing the
      distal box 3 sequence motif of OSMR is required for signal transduction by the
      OSM-specific receptor. In contrast, signaling by LIFR did not display the same
      requirement for receptor domains and was not strictly dependent on the box 3
      elements. The signaling by endogenous LIF and OSM receptors differed from that by
      IL-6R by the prominent activation of STAT5 as shown in the mouse hepatoma cell
      line, Hepa-1. The data suggest that the signaling specificity of the receptors
      for the three cytokines is determined by the composition of the cytoplasmic
      domains associated in the signal-competent receptor complex and that the
      signaling is not identical among these cytokine receptors.

PMID- 9182536
TI  - Identification of domains conferring ligand binding specificity to the prostanoid
      receptor. Studies on chimeric prostacyclin/prostaglandin D receptors.
AB  - To identify domains conferring ligand binding specificity to prostanoid
      receptors, we constructed a series of chimeric receptors by successively
      replacing the regions from the carboxyl-terminal tail of mouse prostacyclin
      (prostaglandin I (PGI)) receptor (mIP) with the corresponding regions of the
      mouse PGD receptor (mDP). The mIP receptor expressed in COS 7 cells bound
      [3H]iloprost, a PGI2 analog, and [3H]PGE1 with Kd values of 13 and 27 nM,
      respectively. This receptor did not bind [3H]PGD2, [3H]PGE2, and [3H]PGF2alpha.
      The mDP receptor bound only [3H]PGD2 with a Kd value of 43 nM. The chimeric IPN
      VII/DPC receptor with replacement of the carboxyl tail of the mIP receptor with
      that of the mDP receptor showed 12-16-fold higher affinities for [3H]iloprost and
      [3H]PGE1 than the mIP receptor. The region extending from the sixth transmembrane
      domain to the carboxyl terminus of the mIP receptor was next replaced with the
      corresponding region of the mDP receptor. This chimeric IPN-V/DPVI-C receptor
      acquired the ability to bind [3H]PGD2 and [3H]PGE2 without decreasing the
      affinities of the mIP receptor to [3H]iloprost and [3H]PGE1. These binding
      characteristics did not change when the fourth and fifth transmembrane domains of
      the mIP receptor were further replaced with the corresponding regions of the mDP
      receptor. However, when the first extracellular to second intracellular loop of
      the mIP receptor containing the third transmembrane domain was further replaced
      with those of the mDP receptor, the affinities for [3H]PGE1, [3H]PGE2, and
      [3H]iloprost were markedly decreased, whereas that for [3H]PGD2 was increased by
      about 2-fold. [3H]PGF2alpha showed no affinity for the mIP, mDP, and all the
      chimeric receptors. These results suggest that the sixth to seventh transmembrane
      domain of the mIP receptor confers the specificity of this receptor to bind
      selectively to PGE1 and not to PGE2 and that the third transmembrane domain of
      the mDP receptor confers the selective binding of PGD2 to this receptor.

PMID- 9182537
TI  - Identification of functional conserved residues of CTP:glycerol-3-phosphate
      cytidylyltransferase. Role of histidines in the conserved HXGH in catalysis.
AB  - The CTP:glycerol-3-phosphate cytidylyltransferase (GCT) of Bacillus subtilis has
      been shown to be similar in primary structure to the CTP:phosphocholine
      cytidylyltransferases of several organisms. To identify the residues of this
      cytidylyltransferase family that function in catalysis, the conserved hydrophilic
      amino acid residues plus a conserved tryptophan of the GCT were mutated to
      alanine. The most dramatic losses in activity occurred with H14A and H17A; these
      histidine residues are part of an HXGH sequence similar to that found in class I
      aminoacyl-tRNA synthetases. The kcat values for H14A and H17A were decreased by
      factors of 5 x 10(-5) and 4 x 10(-4), respectively, with no significant change in
      Km values. Asp-11, which is found near the HXGH sequence in the
      cytidylyltransferases but not aminoacyl-tRNA synthetases, was also important for
      activity, with the D11A mutation decreasing activity by a factor of 2 x 10(-3).
      Several residues found in the sequence RTEGISTT, a signature sequence for this
      cytidylyltransferase family, as well as other isolated residues were also shown
      to be important for activity, with kcat values decreasing by factors of 0.14-4 x
      10(-4). The Km values of three mutant enzymes, D38A, W74A, and D94A, for both CTP
      and glycerol-3-phosphate were 6-130-fold higher than that of the wild-type
      enzyme. Mutant enzymes were analyzed by two-dimensional NMR to determine if the
      overall structures of the enzymes were intact. One of the mutant enzymes, D66A,
      was defective in overall structure, but several of the others, including H14A and
      H17A, were not. These results indicate that His-14 and His-17 play a role in
      catalysis and suggest that their role is similar to the role of the His residues
      in the HXGH sequence in class I aminoacyl-tRNA synthetases, i.e. to stabilize a
      pentacoordinate transition state.

PMID- 9182538
TI  - MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates
      and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated
      protein kinase.
AB  - c-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) are
      mitogen-activated protein kinase (MAPK)-related protein kinases that are involved
      in several cellular events, including growth, differentiation, and apoptosis.
      Mixed lineage kinases (MLKs) form a family of protein kinases sharing two leucine
      zipper-like motifs and a kinase domain whose primary structure is similar to both
      the tyrosine-specific and the serine/threonine-specific kinase classes. We have
      reported that a member of the MLK family, MUK/DLK/ZPK, can activate JNK/SAPK in
      vivo, and here we show that another member of the MLK family, MST/MLK2, activates
      JNK/SAPK. Both MUK/DLK/ZPK and MST/MLK2 cause a slight activation of p38/Mpk2
      when overexpressed in COS-1 cells, whereas MST/MLK2, but not MUK/DLK/ZPK,
      activates extracellular response kinase (ERK) to a certain degree. The activity
      of SEK1/MKK4/JNKK, a MAPK kinase class protein kinase designated as a direct
      activator of JNK/SAPK, is also induced by MUK/DLK/ZPK or MST/MLK2 overexpression.
      Furthermore, recombinant MST/MLK2 produced in bacteria directly phosphorylates
      and activates SEK1/MKK4/JNKK in vitro, showing that MST/MLK2 acts like a MAPK
      kinase kinase. Taken together, these results suggest that MLK family members are
      MAPK kinase kinases preferentially acting on the JNK/SAPK pathway.

PMID- 9182539
TI  - NF-kappaB-mediated induction of mdr1b expression by insulin in rat hepatoma
      cells.
AB  - The expression of P-glycoproteins encoded by the mdr gene family is associated
      with the emergence of multidrug resistance phenotype in animal cells. However,
      the mechanisms controlling the expression of these genes have not been well
      elucidated. Here, we report that the expression of rat mdr1b gene in cultured H-4
      II-E hepatoma cells can be induced by insulin. Transient transfection assays
      using reporter gene constructs containing various 5' mdr1b sequences showed that
      the sequence located between base pairs -243 and -163 is important for insulin's
      induction of mdr1b promoter activity. Further analyses revealed that a NF-kappaB
      binding site (located between base pairs -167 and -158) is required for insulin
      induced promoter activity. Gel mobility shift assay demonstrated that insulin
      stimulates the binding of nuclear p50/p65 subunits to the mdr1b NF-kappaB
      sequence. Cotransfection of plasmids expressing either the p50/p65 NF-kappaB
      subunits or Raf-1 kinase or both resulted in increased expression of the gene
      containing wild-type but not NF-kappaB site-mutated mdr1b promoter. Finally,
      expression of either the antisense p65 subunit of NF-kappaB or dominant negative
      Raf-1 kinase blocked insulin's induction of the mdr1b promoter activity. Taken
      together, our results suggest that the insulin-induced mdr1b expression is
      mediated by transcription factor NF-kappaB via the Raf-1 kinase signaling
      pathway.

PMID- 9182540
TI  - Two activation states of the prohormone convertase PC1 in the secretory pathway.
AB  - PC1, a neuroendocrine member of the prohormone convertase family of serine
      proteinases, is implicated in the processing of proproteins in the secretory
      pathway. PC1 is synthesized as a zymogen and cleaves not only its own profragment
      in the endoplasmic reticulum, but a subset of protein substrates in the Golgi
      apparatus and in the Golgi-distal compartments of the regulated secretory
      pathway. Likewise, mouse PC1 (mPC1) has previously been shown to cleave human
      prorenin in GH4 cells (that contain secretory granules) while being unable to
      cleave prorenin in cells, such as Chinese hamster ovary (CHO) or BSC-40, which
      are devoid of secretory granules. In the current study, we show that removal of a
      C-terminal tail of mPC1 allows the efficient cleavage of prorenin in the
      constitutive secretory pathway of CHO cells. The C-terminal tail thus appears to
      act as an inhibitor of PC1 activity against certain substrates in the endoplasmic
      reticulum and Golgi apparatus, and its removal, which occurs naturally in
      secretory granules, may explain the observed granule-specific processing of
      certain proproteins. These results also demonstrate that PC1 is present in a
      partially active state prior to the secretory granules where it is processed to a
      maximally active state.

PMID- 9182541
TI  - Asparagine 394 in putative helix 11 of the galactose-H+ symport protein (GalP)
      from Escherichia coli is associated with the internal binding site for
      cytochalasin B and sugar.
AB  - The galactose-H+ symport protein (GalP) of Escherichia coli is very similar to
      the human glucose transport protein, GLUT1, and both contain a highly conserved
      Asn residue in predicted helix 11 that is different in a cytochalasin B-resistant
      member of this sugar transport family (XylE). The role of the Asn394 residue
      (which is predicted to be in putative trans-membrane alpha-helix 11) in the
      structure/activity relationship of the D-galactose-H+ symporter (GalP) was
      therefore assessed by measuring the interaction of sugar substrates and the
      inhibitory antibiotics, cytochalasin B, and forskolin with the wild-type and
      Asn394 --> Gln mutant proteins. Steady-state fluorescence quenching experiments
      show that the mutant protein binds cytochalasin B with a Kd 37-53-fold higher
      than the wild type. This low affinity binding was not detected with equilibrium
      binding or photolabeling experiments. In contrast, the mutant protein binds
      forskolin with a Kd similar to that of the wild type and is photolabeled by 3
      125I-4-azido-phenethylamido-7-O-succinyl-desacetyl-forskolin. The mutant protein
      displays an increased amount of steady-state fluorescence quenching with the
      binding of forskolin, suggesting that the substitution of the Asn residue has
      altered the environment of a tryptophan, probably Trp395, in a conformationally
      active region of the protein. Time-resolved fluorescence measurements on the
      mutant protein provided association and dissociation rate constants (k2 and k-2),
      describing the initial interaction of cytochalasin B to the inward-facing binding
      site (Ti), that are decreased (9-fold) and increased (4.9-fold) compared with the
      wild type. This yielded a dissociation constant (K2) for cytochalasin B to the
      inward-facing binding site 44-fold higher than that of the wild type. The binding
      of forskolin gave values for k2 and k-2 3.9- and 3.6-fold lower, respectively,
      yielding a K2 value for Ti similar to that of the wild type. The low overall
      affinity (high Kd) of the mutant protein for cytochalasin B is due mainly to a
      disruption in binding to the Ti conformation. It is proposed that Asn394 forms
      either a direct binding interaction with cytochalasin B or is part of the
      immediate environment of the binding site and that Asn394 is in the immediate
      environment, but not part, of the forskolin binding site. The ability of the
      mutant protein to catalyze energized transport is only mildly impaired with 4.8-
      and 2.1-fold reduction in Vmax/Km values for D-galactose and D-glucose,
      respectively. In stark contrast, the overall Kd describing binding of D-galactose
      and D-glucose to the inward-facing conformation of the mutant and their
      subsequent translocation across the membrane is substantially increased (64-fold
      for D-galactose and 163.3-fold for D-glucose). These data indicate that Asn394 is
      associated with both the cytochalasin B and internal sugar binding sites. This
      conclusion is also supported by data showing that the sugar specificity of the
      mutant protein has been altered for D-xylose. This work powerfully illustrates
      how comparisons of the aligned amino acid sequences of homologous membrane
      proteins of unknown structure and characterization of their phenotypes can be
      used to map substrate and ligand binding sites.

PMID- 9182542
TI  - Entrapment of 6-thiophosphoryl-IMP in the active site of crystalline
      adenylosuccinate synthetase from Escherichia coli.
AB  - Crystal structures of adenylosuccinate synthetase from Escherichia coli complexed
      with Mg2+, 6-thiophosphoryl-IMP, GDP, and hadacidin at 298 and 100 K have been
      refined to R-factors of 0.171 and 0.206 against data to 2.8 and 2.5 A resolution,
      respectively. Interactions of GDP, Mg2+ and hadacidin are similar to those
      observed for the same ligands in the complex of IMP, GDP, NO3-, Mg2+ and
      hadacidin (Poland, B. W., Fromm, H. J. & Honzatko, R. B. (1996). J. Mol. Biol.
      264, 1013-1027). Although crystals were grown from solutions containing 6
      mercapto-IMP and GTP, the electron density at the active site is consistent with
      6-thiophosphoryl-IMP and GDP. Asp-13 and Gln-224 probably work in concert to
      stabilize the 6-thioanion of 6-mercapto-IMP, which in turn is the nucleophile in
      the displacement of GDP from the gamma-phosphate of GTP. Once formed, 6
      thiophosphoryl-IMP is stable in the active site of the enzyme under the
      conditions of the structural investigation. The direct observation of 6
      thiophosphoryl-IMP in the active site is consistent with the putative generation
      of 6-phosphoryl-IMP along the reaction pathway of the synthetase.

PMID- 9182543
TI  - Ribosomal 5 S rRNA maturation in Saccharomyces cerevisiae.
AB  - The maturation of the ribosomal 5 S RNA in Saccharomyces cerevisiae is examined
      based on the expression of mutant 5 S rRNA genes, in vivo, and a parallel
      analysis of RNA processing, in vitro. Both types of analysis indicate that 5 S
      rRNA processing is not dependent on the nucleotide sequence of either the
      external transcribed spacer or the mature 5 S rRNA. The results further indicate
      the RNA is processed by an exonuclease activity which is limited primarily or
      entirely by helix I, the secondary structure formed between the mature and
      interacting termini. The 5 S RNA binding protein (YL3) also appears not to
      influence directly the maturation process, but rather to play a role in
      protecting the rRNA from further degradation by "housekeeping" nucleases. Taken
      together, the results continue to support a "quality control" function which
      helps to ensure that during maturation only normal precursors are processed and
      assembled into active ribosomes.

PMID- 9182544
TI  - Desensitization of N-formylpeptide receptor-mediated activation is dependent upon
      receptor phosphorylation.
AB  - The human N-formylpeptide receptor (FPR) represents one of the most thoroughly
      studied leukocyte chemoattractant receptors. Despite this, little is known about
      the molecular mechanisms involved in the activation and desensitization of this
      receptor. To assess the role of phosphorylation in receptor function, U937
      promonocytic cells were stably transfected to express the recombinant human FPR.
      Three mutant forms of the FPR lacking specific serine and threonine residues in
      the receptor C terminus were studied with respect to activation and
      desensitization. Replacement of all 11 serine and threonine residues within the C
      terminus by alanine and glycine residues (DeltaST) resulted in a receptor capable
      of ligand binding and G protein activation similar to the wild-type receptor.
      However, whereas the wild-type FPR was phosphorylated on both serine and
      threonine residues upon exposure to agonist and displayed a significantly reduced
      ability to stimulate G protein-mediated GTP hydrolysis upon subsequent exposure
      to agonist, DeltaST demonstrated a complete lack of phosphorylation and displayed
      little alteration in its ability to stimulate G protein-mediated GTP hydrolysis
      upon a subsequent exposure to agonist. In addition to desensitization of G
      protein-mediated GTP hydrolysis, calcium mobilization was assayed to test whether
      desensitization occurred at a site distal to G protein activation. However, as
      observed with G protein activation, DeltaST underwent no desensitization of the
      calcium mobilization response upon a second exposure to agonist. To define more
      precisely the role of specific serine and threonine residues, two additional
      mutants were analyzed. Replacement either of Ser328, Thr329, Thr331, and Ser332
      (mutant A) or of Thr334, Thr336, Ser338, and Thr339 (mutant B) resulted in
      functional receptors that exhibited approximately 50% the level of
      phosphorylation following stimulation. Whereas mutant A, like DeltaST, could not
      be significantly desensitized by exposure to agonist, mutant B exhibited partial
      desensitization. These results indicate that phosphorylation of the FPR is a
      necessary and sufficient step in cellular desensitization, that multiple
      phosphorylation sites are involved, and that redundant desensitization does not
      occur downstream of G protein activation in the signaling cascade.

PMID- 9182545
TI  - Inhibition of protein phosphatase activity induces p53-dependent apoptosis in the
      absence of p53 transactivation.
AB  - Inhibitors of type 1 and type 2A protein phosphatases were used to examine the
      involvement of protein phosphorylation in regulating the functions of endogenous
      p53. Exposure of Balb/c 3T3 cells to okadaic acid, an inhibitor of protein
      phosphatases 1 and 2A, increased the phosphorylation of p53 without changing p53
      levels. Okadaic acid treatment enhanced the binding of p53 to a consensus DNA
      target sequence and caused a 5-8-fold increase in p53 transcriptional activity.
      Transient expression of SV40 small tumor antigen, a specific inhibitor of protein
      phosphatase 2A, caused a 4-fold increase in p53 transcriptional activity.
      Incubation of Balb/c 3T3 cells with okadaic acid also induced programmed cell
      death in a dose- and time-dependent manner. Decreases in viability, morphological
      changes, and the appearance of DNA fragmentation were dependent on p53 since
      cells lacking functional p53 were resistant to okadaic acid-induced apoptosis.
      The p53-dependent apoptosis induced by okadaic acid was rapid and did not require
      p53 transcriptional activity. The fact that SV40 small tumor antigen did not
      induce apoptosis provides additional evidence that p53 transcriptional activity
      is not sufficient for p53-mediated apoptosis. These results indicate that
      signaling pathways involving protein phosphorylation play critical roles in
      controlling the apoptotic activity of p53. Furthermore, a basal level of protein
      phosphatase 1 or 2A activity is necessary to prevent p53-dependent apoptosis.

PMID- 9182546
TI  - In situ formation of protease-resistant prion protein in transmissible spongiform
      encephalopathy-infected brain slices.
AB  - The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal
      neurodegenerative diseases that are characterized by the conversion of the normal
      host cellular prion protein (PrPC), to the abnormal protease-resistant prion
      protein isoform (PrP-res). It has been proposed, though not proven, that the
      infectious TSE agent consists solely of PrP-res and that PrP-res-induced
      conformational conversion of PrPC to additional PrP-res represents agent
      replication. In this study we demonstrate in situ conversion of protease
      sensitive PrPC to PrP-res in TSE-infected brain slices. One step in this process
      is the binding of soluble PrPC to endogenous PrP-res deposits. The newly formed
      PrP-res associated with the slices in a pattern that correlated with the pre
      existing brain distribution of PrP-res. Punctate in situ PrP conversion was
      observed in brain regions containing PrP-res amyloid plaques, and a more
      dispersed conversion product was detected in areas containing diffuse PrP-res
      deposits. These studies provide direct evidence that PrP-res formation involves
      the incorporation of soluble PrPC into both nonfibrillar and fibrillar PrP-res
      deposits in TSE-infected brain. Our findings suggest that the in situ PrP
      conversion reaction leads to additional polymerization of endogenous PrP-res
      aggregates and is analogous to the process of PrP-res fibril and subfibril growth
      in vivo.

PMID- 9182548
TI  - Influence of the A helix structure on the polymerization of hemoglobin S.
AB  - Hb S variants containing Lys-beta132 --> Ala or Asn substitutions were engineered
      to evaluate the consequences of the A helix destabilization in the polymerization
      process. Previous studies suggested that the loss of the Glu-beta7-Lys-beta132
      salt bridge in the recombinant Hb betaE6V/E7A could be responsible for the
      destabilization of the A helix. The recombinant Hb (rHb) S/beta132 variants
      polymerized with an increased delay time as well as decreased maximum absorbance
      and Hb solubility values similar to that of Hb S. These data indicate that the
      strength of the donor-acceptor site interaction may be reduced due to an altered
      conformation of the A helix. The question arises whether this alteration leads to
      a true inhibition of the polymerization process or to qualitatively different
      polymers. The oxygen affinity of the beta132 mutated rHbs was similar to that of
      Hb A and S, whereas the cooperativity and effects of organic phosphates were
      reduced. This could be attributed to modifications in the central cavity due to
      loss of the positively charged lysine. Since Lys-beta132 is involved in the
      stabilization of the alpha1-beta1 interface, the loss of the beta132(H10)
      beta128(H6) salt bridge may be responsible for the marked thermal instability of
      the beta132 mutated rHbs.

PMID- 9182547
TI  - Human IgGFc binding protein (FcgammaBP) in colonic epithelial cells exhibits
      mucin-like structure.
AB  - Cloning a cDNA for human IgGFc binding protein (FcgammaBP) from human colonic
      epithelial cells reveals an mRNA and coding region of 17 and 16.2 kilobases,
      respectively. The predicted amino acid sequence contains 12 occurrences of a 400
      amino acid cysteine-rich unit resembling that found in mucin. A motif (CGLCGN) in
      FcgammaBP is conserved in MUC2 and prepro-von Willebrand factor. The N-terminal
      450-amino acid sequences are necessary and sufficient to confer IgG Fc binding
      activity. FcgammaBP mRNA is expressed only in placenta and colonic epithelial
      cells. These results suggest that FcgammaBP may play an important role in immune
      protection and inflammation in the intestines of primates.

PMID- 9182549
TI  - Organelle-specific targeting of protein kinase AII (PKAII). Molecular and in situ
      characterization of murine A kinase anchor proteins that recruit regulatory
      subunits of PKAII to the cytoplasmic surface of mitochondria.
AB  - Experiments were designed to test the idea that A kinase anchor proteins (AKAPs)
      tether regulatory subunits (RII) of protein kinase AII (PKAII) isoforms to
      surfaces of organelles that are bounded by phospholipid bilayers. S-AKAP84, one
      of three RII-binding proteins encoded by a single-copy murine gene, was studied
      as a prototypic organelle-associated AKAP. When S-AKAP84 was expressed in HEK293
      cells, the anchor protein was targeted to mitochondria and excluded from other
      cell compartments. The RII tethering site is located in the cytoplasm adjacent to
      the mitochondrial surface. Endogenous RII subunits are not associated with
      mitochondria isolated from control cells. Expression of S-AKAP84 in transfected
      HEK293 cells triggered a redistribution of 15% of total RII to mitochondria.
      Thus, the tethering region of the organelle-inserted anchor protein is properly
      oriented and avidly binds RII (PKAII) isoforms in intact cells. Two critical
      domains in S-AKAP84 were mapped. Residues 1 to 30 govern insertion of the
      polypeptide into the outer mitochondrial membrane; amino acids 306-325 constitute
      the RII-binding site. Properties established for S-AKAP84 in vitro and in situ
      strongly suggest that a physiological function of this protein is to concentrate
      and immobilize RII (PKAII) isoforms at the cytoplasmic face of a phospholipid
      bilayer.

PMID- 9182550
TI  - The expression of the gene coding for the antibacterial peptide LL-37 is induced
      in human keratinocytes during inflammatory disorders.
AB  - The epithelia constitute a major barrier to the environment and provide the first
      line of defense against invading microbes. Antimicrobial peptides are emerging as
      participants in the defense system of epithelial barriers in general. Originally
      we isolated the human antimicrobial peptide LL-37 from granulocytes. The gene
      (CAMP or cathelicidin antimicrobial peptide) coding for this peptide belongs to
      the cathelicidin family, whose members contain a conserved pro-part of the
      cathelin type. The human genome seems to have only one gene of this family,
      whereas some mammalian species have several cathelicidin genes. In the present
      work we demonstrate up-regulation of this human cathelicidin gene in inflammatory
      skin disorders, whereas in normal skin no induction was found. By in situ
      hybridization and immunohistochemistry the transcript and the peptide were
      located in keratinocytes throughout the epidermis of the inflammatory regions. In
      addition, the peptide was detected in partially pure fractions derived from
      psoriatic scales by immunoblotting. These fractions also exhibited antibacterial
      activity. We propose a protective role for LL-37, when the integrity of the skin
      barrier is damaged, participating in the first line of defense, and preventing
      local infection and systemic invasion of microbes.

PMID- 9182551
TI  - Different in vitro and in vivo targeting properties of the transit peptide of a
      chloroplast envelope inner membrane protein.
AB  - The triose phosphate 3-phosphoglycerate phosphate translocator (TPT) is a
      chloroplast envelope inner membrane protein whose transit peptide has structural
      properties typical of a mitochondrial presequence. To study the TPT transit
      peptide in more detail, we constructed two chimeric genes encompassing the TPT
      transit peptide and either 5 or 23 amino-terminal residues of the mature TPT,
      both linked to the reporter chloramphenicol acetyltransferase (cat) gene. The
      precursors were synthesized in vitro and translocated to and processed in
      purified plant mitochondria. However, this import was not specific since both
      precursors were also imported into isolated chloroplasts. To extend this analysis
      in vivo, the chimeric genes were introduced into tobacco by genetic
      transformation. Analysis of CAT distribution in subcellular fractions of
      transgenic plants did not confirm the data obtained in vitro. With the construct
      retaining only 5 residues of the mature TPT, CAT was found in the cytosolic
      fraction. Extension of the TPT transit peptide to 23 residues of the mature TPT
      allowed specific import and processing of CAT into chloroplasts. These results
      indicate that, despite its unusual structure, the TPT transit peptide is able to
      target a passenger protein specifically into chloroplasts, provided that NH2
      terminal residues of the mature TPT are still present. The discrepancy between
      the in vitro and in vivo data suggests that the translocation machinery is more
      stringent in the latter case and that sorting of proteins might not be addressed
      adequately by in vitro experiments.

PMID- 9182552
TI  - Secretion of human furin into mouse milk.
AB  - We have previously described the expression of the human proprotein convertase
      furin or paired basic amino acid-cleaving enzyme, in mice transgenic for paired
      basic amino acid-cleaving enzyme and human Protein C (HPC). Here we show 100-fold
      or higher expression of furin in the mammary gland, compared with endogenous
      furin. Furin and recombinant HPC were detected in the same regions of the mammary
      gland and regulated similar to the endogenous whey acidic protein. In addition to
      the expected intracellular localization, furin was secreted into the milk as an
      80-kDa form lacking the transmembrane and cytoplasmic domains. Furin present at
      levels of up to 40,000 units/ml milk cleaved the t-butoxycarbonyl-RVRR-AMC
      substrate with a Km of 32 microM, and processed the recombinant HPC precursor at
      the appropriate sites. Surprisingly, the expression of an active protease was not
      toxic to the mammary gland. This is a rare example of an animal model secreting
      active truncated forms of a processing endoprotease into a bodily fluid.

PMID- 9182553
TI  - In vivo determination of replication origins of human mitochondrial DNA by
      ligation-mediated polymerase chain reaction.
AB  - A large part of replication is aborted in human mitochondria, the result being a
      D-loop. As few attempts have been made to distinguish free 5' ends of true
      replicate from those of abortive ones, we examined the 5' ends of true replicate
      of human mitochondrial DNA at one nucleotide resolution in vivo by making use of
      ligation-mediated polymerase chain reaction. The distribution and relative
      amounts of origins of the true replicate are exactly the same as those of total
      newly synthesized heavy strands, which means that the abortion of replication is
      independent of 5' ends. Treatment of DNA with RNase H frees 5' ends on both heavy
      and light strands. This is the first in vivo evidence for covalently attached
      primer RNA to nascent strand in human mitochondrial DNA.

PMID- 9182554
TI  - Cloning and molecular characterization of plant aldehyde oxidase.
AB  - Primary structural information of a plant aldehyde oxidase (AO), which was
      purified from maize coleoptiles using indole-3-acetaldehyde as a substrate, was
      obtained by sequencing a series of cleavage peptides, permitting the cloning of
      the corresponding cDNA (zmAO-1). The complete nucleotide sequence was determined;
      the deduced amino acid sequence encodes a protein of 1358 amino acid residues of
      Mr 146,681, which is consistent with the size of the AO monomeric subunit. There
      is a significant similarity with AO from mammals and xanthine dehydrogenases from
      various sources. The maize AO polypeptide contains consensus sequences for iron
      sulfur centers and a putative molybdopterin cofactor-binding domain. In addition,
      another cDNA (zmAO-2), highly homologous to zmAO-1 at both the nucleotide and
      amino acid sequence levels, was cloned. zmAO-2 would encode a protein of 1349
      amino acid residues of Mr 145,173 and has molecular characteristics similar to
      those of zmAO-1. zmAO-1 was expressed at a high level in roots, which was closely
      correlated with immunoblotting results using antiserum raised against the
      purified maize AO protein, whereas zmAO-2 was expressed at a higher level in
      coleoptiles than in roots. We propose each zmAO may have a unique function during
      plant development.

PMID- 9182555
TI  - Modulation of the P1 plasmid partition protein ParA by ATP, ADP, and P1 ParB.
AB  - ParA is an essential P1 plasmid partition protein. It represses transcription of
      the par genes (parA and parB) and is also required for a second, as yet undefined
      step in partition. ParA is a ParB-stimulated ATPase that binds to a specific DNA
      site in the par promoter region. ATP binding and hydrolysis by ParA affect ParA
      activities in vitro. ATP and ADP binding stimulate ParA DNA binding and
      dimerization; however, ATP hydrolysis has a negative effect on DNA binding. Our
      current experiments reveal that ATP binding and hydrolysis affect ParA
      conformation and ParA sensitivity to ParB. Nucleotide binding assays show that
      ParA binds ATP better than ADP (Kd values of 33 and 50 microM, respectively).
      Interaction with these nucleotides as well as ATP hydrolysis by ParA alter ParA
      conformation as established by CD and ParA sensitivity to heat denaturation.
      Finally, we show that ParB stimulates ParA DNA binding. This stimulation requires
      ATP hydrolysis in vitro, suggesting that one role for ATP hydrolysis in vivo is
      to make ParA repressor sensitive to ParB. Our observations lead to the suggestion
      that ATP binding and hydrolysis have separable roles in ParA repressor function
      and perhaps in ParA partition functions as well.

PMID- 9182556
TI  - Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and
      erythroid differentiation in K562 cells.
AB  - Acquisition of heat shock factor 2 (HSF2) DNA binding activity is accompanied by
      induced transcription of heat shock genes in hemin-treated K562 cells undergoing
      erythroid differentiation. Previous studies revealed that HSF2 consists of two
      alternatively spliced isoforms, HSF2-alpha and HSF2-beta, whose relative
      abundance is developmentally regulated and varies between different tissues. To
      investigate whether the molar ratio of HSF2-alpha and HSF2-beta isoforms is
      crucial for the activation of HSF2 and whether the HSF2 isoforms play
      functionally distinct roles during the hemin-mediated erythroid differentiation,
      we generated cell clones expressing different levels of HSF2-alpha and HSF2-beta.
      We show that in parental K562 cells, the HSF2-alpha isoform is predominantly
      expressed and HSF2 can be activated upon hemin treatment. In contrast, when HSF2
      beta is expressed at levels exceeding those of endogenous HSF2-alpha, the hemin
      induced DNA binding activity and transcription of heat shock genes are repressed,
      whereas overexpression of HSF2-alpha results in an enhanced hemin response.
      Furthermore, the hemin-induced accumulation of globin, known as a marker of
      erythroid differentiation, is decreased in cells overexpressing HSF2-beta. We
      suggest that HSF2-beta acts as a negative regulator of HSF2 activity during hemin
      mediated erythroid differentiation of K562 cells.

PMID- 9182557
TI  - Defining the minimal domain of the Plasmodium falciparum protein MESA involved in
      the interaction with the red cell membrane skeletal protein 4.1.
AB  - During part of its life cycle, the protozoan parasite Plasmodium falciparum lives
      within the human red blood cell and modifies both the structural and functional
      properties of the red cell. It does this by synthesizing a number of polypeptides
      that it transports into the red cell cytoplasm and to the red cell membrane. One
      of these transported proteins, MESA (mature parasite-infected erythrocyte surface
      antigen), is anchored to the red cell membrane by noncovalent interaction with
      erythrocyte protein 4.1. We have utilized a combination of in vitro transcription
      and translation and a membrane binding assay to identify the protein sequence
      involved in anchoring MESA to the membrane. Labeled fragments of different
      regions of the MESA protein were evaluated for their ability to bind to inside
      out vesicle membrane preparations of human red cells. Binding was dependent on
      the presence of red cell membrane proteins and was abolished either by trypsin
      treatment or by selective depletion of membrane proteins. Binding was specific
      and could be inhibited by the addition of competing protein, with an IC50 of (6.3
      +/- 1.2) x 10(-7) M, indicative of a moderate affinity interaction. Fractionation
      studies demonstrated that binding fragments interacted most efficiently with
      membrane protein fractions that had been enriched in protein 4.1. Binding
      inhibition experiments using synthetic peptides identified the binding domain of
      MESA for protein 4.1 as a 19-residue sequence near the amino terminus of MESA, a
      region capable of forming an amphipathic helix.

PMID- 9182558
TI  - Binding of cationic alpha-helical peptides to plasmid DNA and their gene transfer
      abilities into cells.
AB  - Polycationic reagents such as cationic lipids and poly-L-lysine are widely used
      for gene transfer into cells in vitro and show promise as vectors for in vivo
      gene therapy applications as nonviral gene transfer techniques. We have developed
      a novel transfection method using cationic amphiphilic alpha-helical
      oligopeptides with repeated sequences. Oligopeptide has the advantages of being
      easily designed and modified because of its simple structure. In this study, we
      synthesized five kinds of peptides of which the total chain length and the width
      of the hydrophobic region were changed. The binding of the peptides to plasmid
      DNA was evaluated by agarose gel electrophoresis. It was found that the long
      and/or hydrophobic peptides can strongly bind to the DNA. The formation of large
      aggregates with a 0.5-5-microm diameter, which consisted of the long peptides and
      the DNA, was observed by electron microscopy. The transfection abilities of the
      peptides were determined by the expression of luciferase from its cDNA in COS-7
      cells. The long peptides showed high transfection abilities. As a result, it
      could be said that the transfection ability of these peptides was parallel to
      their ability to form aggregates with DNA. Furthermore, the transfection ability
      was increased by the addition of chloroquine in the transfection procedure. This
      result indicated that the internalization of the peptide-DNA aggregates would be
      mediated by the endocytosis pathway.

PMID- 9182559
TI  - Targeting of endopeptidase 24.16 to different subcellular compartments by
      alternative promoter usage.
AB  - Endopeptidase 24.16 or mitochondrial oligopeptidase, abbreviated here as EP 24.16
      (MOP), is a thiol- and metal-dependent oligopeptidase that is found in multiple
      intracellular compartments in mammalian cells. From an analysis of the
      corresponding gene, we found that the distribution of the enzyme to appropriate
      subcellular locations is achieved by the use of alternative sites for the
      initiation of transcription. The pig EP 24.16 (MOP) gene spans over 100 kilobases
      and is organized into 16 exons. The core protein sequence is encoded by exons 5
      16 which match perfectly with exons 2-13 of the gene for endopeptidase 24.15,
      another member of the thimet oligopeptidase family. These two sets of 11 exons
      share the same splice sites, suggesting a common ancestor. Multiple species of
      mRNA for EP 24.16 (MOP) were detected by the 5'-rapid amplification of cDNA ends
      and they were shown to have been generated from a single gene by alternative
      choices of sites for the initiation of transcription and splicing. Two types of
      transcript were prepared, corresponding to transcription from distal and proximal
      sites. Their expression in vitro in COS-1 cells indicated that they encoded two
      isoforms (long and short) which differed only at their amino termini: the long
      form contained a cleavable mitochondrial targeting sequence and was directed to
      mitochondria; the short form, lacking such a signal sequence, remained in the
      cytosol. The complex structure of the EP 24.16 (MOP) gene thus allows, by
      alternative promoter usage, a fine transcriptional regulation of coordinate
      expression, in the different subcellular compartments, of the two isoforms
      arising from a single gene.

PMID- 9182560
TI  - Purification, cloning, and functional expression of dihydroneopterin triphosphate
      2'-epimerase from Escherichia coli.
AB  - Dihydroneopterin triphosphate (H2NTP) 2'-epimerase from Escherichia coli
      catalyzes the epimerization of H2NTP to dihydromonapterin triphosphate (H2MTP).
      The enzyme was purified 954-fold to apparent homogeneity by a combination of
      ammonium sulfate fractionation and column chromatography of Cibacron blue 3GA dye
      ligand, phenyl-Sepharose CL-4B, methotrexate-agarose, and Superdex 200 HR 10/30
      FPLC column. The molecular mass of the epimerase determined on a Superdex column
      was 82.6 kDa, while the subunit molecular mass determined on SDS-polyacrylamide
      gel electrophoresis was 13.7 kDa. This implies that the epimerase most probably
      exists as homohexamer. The 20-amino acid sequence from the N terminus was
      determined (AQPAAIIRIKNLRLRTFIGI). Based on this sequence, the gene encoding the
      epimerase was cloned using a simple polymerase chain reaction approach.
      Translation of the nucleotide sequence of the cloned gene revealed the presence
      of an open reading frame containing 120 amino acids with a predicted molecular
      mass of 13,993 Da. The epimerase gene located in a 2.3-kilobase BamHI-EcoRI
      fragment from Kohara's clone 406 was overexpressed 300-fold, which was confirmed
      by the prominent increase in the 14-kDa protein band on SDS-polyacrylamide
      electrophoresis gels. It showed no homology with the sequences of isomerases or
      other enzymes in GenBank/EMBL data bases.

PMID- 9182561
TI  - RNA polymerase switches between inactivated and activated states By translocating
      back and forth along the DNA and the RNA.
AB  - Important regulatory events in both prokaryotic and eukaryotic transcription are
      currently explained in terms of an inchworming model of elongation. In this
      model, RNA extension is carried out by a mobile catalytic center that, at certain
      DNA sites, advances within stationary RNA polymerase. This idea emerged from the
      observation that footprints of individual elongation complexes, halted in vitro
      at consecutive DNA positions, can remain fixed on the template for several
      contiguous nucleotide additions. Here, we examine in detail the structural
      transitions that occur immediately after the enzyme stops at sites where
      discontinuous advancement of RNA polymerase is observed. We demonstrate that
      halting at such special sites does not "freeze" RNA polymerase at one location
      but induces it to leave its initial position and to slide backward along the DNA
      and the RNA without degrading the transcript. The resulting loss of contact
      between the RNA 3'-hydroxyl and the enzyme's catalytic center leads to temporary
      loss of the catalytic activity. This process is equilibrated with enzyme return
      to the original location, so that RNA polymerase is envisaged as an oscillating
      object switching between catalytically active and inactive states. The retreated
      isoform constitutes a principal intermediate in factor-induced endonucleolytic
      RNA cleavage. These oscillations of RNA polymerase can explain its apparent
      discontinuous advancement, which had been interpreted as indicating flexibility
      within the enzyme.

PMID- 9182562
TI  - Deletion analysis of Qbeta replicase. Participation of the carboxyl-terminal
      region of the beta-subunit protein in template recognition.
AB  - We have analyzed one of the functional domains of Qbeta replicase, an RNA
      dependent RNA polymerase of RNA coliphage Qbeta. Deletion mapping analysis of the
      carboxyl-terminal region of the beta-subunit protein revealed that the terminal
      18 amino acid residues (positions 571-588) are dispensable for the replicase
      reaction. Subsequent deletions up to the Ala-565 residue reduced the RNA
      polymerizing activity of the replicase in vivo but increased it in vitro. The
      mutant replicases with enhanced in vitro RNA polymerizing activity were found to
      have relaxed template specificity for ribosomal RNAs and cellular RNAs as well as
      Qbeta RNA. Deletions beyond the Ile-564 residue abolished both the RNA
      polymerizing activity and the binding ability to midivariant (MDV)-poly(+) RNA, a
      derivative of a natural template for Qbeta replicase, MDV-1 RNA. These results
      suggest that the carboxyl-terminal part of the beta-subunit participates in RNA
      recognition of Qbeta replicase.

PMID- 9182563
TI  - A novel class of GABAA receptor subunit in tissues of the reproductive system.
AB  - A novel subunit of the gamma-aminobutyrate, type A (GABAA) receptor family has
      been identified in human and rat tissues. The subunit displays 30-40% amino acid
      identity with known family members and represents a distinct subunit class
      (termed pi). Transcripts of the pi subunit were detected in several human tissues
      and were particularly abundant in the uterus. The pi subunit protein can assemble
      with known GABAA receptor subunits and confer unique ligand binding properties to
      the recombinant receptors in which it combines. Most notably, the presence of the
      pi subunit alters the sensitivity of recombinant receptors to the endogenous
      steroid, pregnanolone. Identification of the pi subunit indicates a new target
      for pharmacological manipulation of GABAA receptors that are located outside of
      the central nervous system.

PMID- 9182564
TI  - Differential replication of a single N-2-acetylaminofluorene lesion in the
      leading or lagging strand DNA in a human cell extract.
AB  - DNA replication in eucaryotic cells is a complex process involving a variety of
      proteins that synthesize the leading and lagging strand in an asymmetric,
      coordinated manner. To investigate the effect of this asymmetry on the
      translesion synthesis of bulky lesions, we have constructed SV40 origin
      containing plasmids with site-specific N-2-acetylaminofluorene adduct on either
      leading or lagging strand templates. These plasmids have been incubated with DNA
      replication-competent extracts made from human HeLa cells. Two-dimensional
      agarose gel electrophoresis analyses reveal a strong blockage of fork progression
      only when the N-2-acetylaminofluorene adduct is located on the leading strand
      template. Morever, the analysis revealed that replication with HeLa cell extracts
      of SV40 origin-dependent plasmids functions in both directions from the origin
      with equal efficiency but, probably due to an important asynchrony at the
      formation of the two forks, proceeds unidirectionally for a large number of
      individual molecules. The validity of the in vitro replication approach to study
      the fidelity of both leading- and lagging strand synthesis is discussed with
      regard to these new data.

PMID- 9182565
TI  - A yeast ATP-binding cassette-type protein mediating ATP-dependent bile acid
      transport.
AB  - ATP-dependent transport of bile acids is a key determinant of bile flow in
      mammalian liver and is associated with cholesterol excretion, gallstone
      formation, and numerous inherited and acquired hepatobiliary diseases. Secretory
      vesicles and a vacuole enriched fraction purified from Saccharomyces cerevisiae
      also exhibit ATP-dependent bile acid transport. ATP-dependent transport of bile
      acids by the vacuolar fraction was independent of the vacuolar proton ATPase,
      responded to changes in the osmotically sensitive intravesicular space, and was
      saturable, exhibiting a Km of 63 microM for taurocholate. The BAT1 (bile acid
      transporter) gene was isolated from yeast DNA by polymerase chain reaction
      amplification using degenerate oligonucleotides hybridizing to conserved regions
      of ABC-type proteins. ATP-dependent bile acid transport was abolished when the
      BAT1 coding region was deleted from the genome and restored upon reintroduction
      of the gene. The deduced amino acid sequence predicts that Bat1p is an ABC-type
      protein 1661 amino acids in length, similar to mammalian cMOAT/cMRP1 and MRP1
      transporters, yeast Ycf1p, and two yeast proteins of unknown function.
      Information obtained from the yeast BAT1 gene may aid identification of the gene
      encoding the mammalian bile acid transporter.

PMID- 9182566
TI  - Stimulation of interleukin-8 production by okadaic acid and vanadate in a human
      promyelocyte cell line, an HL-60 subline. Possible role of mitogen-activated
      protein kinase on the okadaic acid-induced NF-kappaB activation.
AB  - Most types of cells can produce interleukin (IL)-8 in response to various
      inflammatory stimuli. To study the role of protein phosphatases in the signal
      transduction leading to IL-8 production, a subline of HL-60 (C-15) was treated
      with okadaic acid (OA) and sodium orthovanadate (VA), inhibitors of
      phosphoserine/phosphothreonine phosphatase and phosphotyrosine phosphatase,
      respectively. Both OA and VA dramatically increased IL-8 secretion up to 200-fold
      in the HL-60 cells. OA and VA stimulation was accompanied by a marked increase in
      IL-8 mRNA expression and also by activation of a transcription factor, NF-kappaB.
      In addition, an essential role of the NF-kappaB site in the IL-8 gene activation
      was confirmed by the chloramphenicol acetyltransferase assay. IL-8 production by
      OA or VA was inhibited by protein kinase inhibitors, including staurosporine, H
      7, K252a, herbimycin A, and genistein. Both OA and VA induced significant
      tyrosine phosphorylation of p44, which was presumed to be Erk1, a member of the
      mitogen-activated protein kinase family, with concomitant activation of the
      mitogen-activated protein kinase activity. In parallel, rapid degradation of
      IkappaB-alpha, an inhibitory component of NF-kappaB, was observed. Since OA
      activated Erk1 phosphorylated recombinant IkappaB-alpha in vitro, we assumed that
      Erk1 is involved in the phosphorylation and subsequent degradation of IkappaB
      alpha, thus leading to the activation of IL-8 gene transcription.

PMID- 9182567
TI  - Purification, cDNA cloning, and characterization of a new serpin with
      megakaryocyte maturation activity.
AB  - A new member of the serine protease inhibitor (serpin) superfamily with
      megakaryocyte maturation activity was purified, and its cDNA was cloned and
      characterized. The predicted amino acid sequence consisting of 380 residues was
      unique and was 38% identical to the serpin plasminogen activator inhibitor type 2
      (PAI-2). The recombinant factor expressed in Chinese hamster ovary cells showed
      species-specific activity on the induction of megakaryocyte maturation in vitro.
      When injected into mice, the factor indeed elicited an increase in the number of
      platelets in plasma. The sequence alignment indicated that the factor possessed a
      lysine residue at the P1 position, suggesting that it might function as an
      inhibitor of Lys-specific proteases. Although we could not show any inhibitory
      activities toward several known Lys-specific proteases, we detected the activity
      toward protease activity present in the culture supernatant of COLO 201 cells.
      These results suggested that the protein might influence the maturation of
      megakaryocytes via action as a serpin.

PMID- 9182568
TI  - The Arabidopsis thaliana FPS1 gene generates a novel mRNA that encodes a
      mitochondrial farnesyl-diphosphate synthase isoform.
AB  - The enzyme farnesyl-diphosphate synthase (FPS; EC 2.5.1.1./EC 2.5.1. 10)
      catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and
      dimethylallyl diphosphate. FPS is considered to play a key role in isoprenoid
      biosynthesis. We have reported previously that Arabidopsis thaliana contains two
      differentially expressed genes, FPS1 and FPS2, encoding two highly similar FPS
      isoforms, FPS1 and FPS2, (Cunillera, N., Arro, M., Delourme, D., Karst, F.,
      Boronat, A., and Ferrer, A. (1996) J. Biol. Chem. 271, 7774-7780). In this paper
      we report the characterization of a novel Arabidopsis FPS mRNA (FPS1L mRNA)
      derived from the FPS1 gene. A cDNA corresponding to the FPS1L mRNA was cloned
      using a reverse transcription-polymerase chain reaction strategy. Northern blot
      analysis showed that the two FPS1-derived mRNAs are differentially expressed. The
      FPS1L mRNA accumulates preferentially in inflorescences, whereas the previously
      reported FPS1 mRNA (FPS1S mRNA) is predominantly expressed in roots and
      inflorescences. FPS1L mRNA contains an in-frame AUG start codon located 123
      nucleotides upstream of the AUG codon used in the translation of the FPS1S
      isoform. Translation of the FPS1L mRNA from the upstream AUG codon generates a
      novel FPS1 isoform (FPS1L) with an NH2-terminal extension of 41 amino acid
      residues, which has all the characteristics of a mitochondrial transit peptide.
      The functionality of the FPS1L NH2-terminal extension as a mitochondrial transit
      peptide was demonstrated by its ability to direct a passenger protein to yeast
      mitochondria in vivo and by in vitro import experiments using purified plant
      mitochondria. The Arabidopsis FPS1L isoform is the first FPS reported to contain
      a mitochondrial transit peptide.

PMID- 9182569
TI  - Different thresholds in the responses of two heat shock transcription factors,
      HSF1 and HSF3.
AB  - Avian cells express three HSF genes encoding a unique factor, HSF3, as well as
      homologues of mammalian HSF1 and HSF2. HSF1 is the major factor that mediates the
      heat shock signal in mammalian cells. We reported previously that cHSF3, as well
      as cHSF1, is activated by heat shock in chicken cells. In this study, we examined
      the functional differences between cHSF1 and cHSF3. Comparison of the heat
      inducible DNA binding activity of cHSF1 with cHSF3 at various temperatures
      revealed that the latter was activated at higher temperatures than the former. At
      a mild heat shock, such as 41 degrees C, only cHSF1 was activated, whereas both
      cHSF1 and cHSF3 were activated following a severe heat shock at 45 degrees C.
      Heat-inducible nuclear translocation and trimerization were accompanied by DNA
      binding activity. We also observed that cHSF3 was activated by treating cells
      with higher concentrations of sodium arsenite compared to cHSF1. The DNA binding
      activity of cHSF3 by severe heat shock lasted for a longer period than that of
      cHSF1. Interestingly, the total amount of cHSF3 increased only upon severe heat
      shock, whereas that of HSF1 decreased. Substantial amounts of cHSF3 remained in
      the soluble fraction under severe heat shock, whereas cHSF1 rapidly moved to the
      insoluble fractions in that conditions. Comparison of transcriptional activity of
      the activation domains of cHSF1 and cHSF3 revealed that the activity of cHSF3 was
      as strong as that of cHSF1. These findings indicate that there are different
      thresholds for cHSF1 and cHSF3 and that cHSF3 is involved in the persistent and
      burst activation of stress genes upon severe stress in chicken cells.
      Pretreatment of cycloheximide elevated the threshold concentrations of arsenite
      of both factors. This suggests that denaturation of nascent polypeptides could be
      the first trigger for the activation of both factors, and the pathways for
      activation of cHSF1 and cHSF3 may be identical, or at least share some common
      mechanisms.

PMID- 9182570
TI  - Coordinate expression of alpha-tropomyosin and caldesmon isoforms in association
      with phenotypic modulation of smooth muscle cells.
AB  - Isoform diversity of tropomyosin is generated from the limited genes by a
      combination of differential transcription and alternative splicing. In the case
      of the alpha-tropomyosin (alpha-TM) gene, exon 2a rather than exon 2b is
      specifically spliced in alpha-TM-SM mRNA, which is one of the major tropomyosin
      isoforms in smooth muscle cells. Here we demonstrate that expressions of alpha
      tropomyosin and caldesmon isoforms are coordinately regulated in association with
      phenotypic modulation of smooth muscle cells. Molecular cloning and Western and
      Northern blottings have revealed that in addition to the down-regulation of beta
      TM-SM, alpha-TM-SM converted to alpha-TM-F1 and alpha-TM-F2 by a selectional
      change from exon 2a to exon 2b during dedifferentiation of smooth muscle cells in
      culture. Simultaneously, a change of caldesmon isoforms from high Mr type to low
      Mr type was also observed by alternative selection between exons 3b and 4 in the
      caldesmon gene during this process. In contrast, cultured smooth muscle cells
      maintaining a differentiated phenotype continued to express alpha-TM-SM, beta-TM
      SM, and high Mr caldesmon. In situ hybridization revealed specific coexpression
      of alpha-TM-SM and high Mr caldesmon in smooth muscle in developing embryos.
      These results suggest a common splicing mechanism for phenotype-dependent
      expression of tropomyosin and caldesmon isoforms in both visceral and vascular
      smooth muscle cells.

PMID- 9182571
TI  - Regulation of the human chorionic gonadotropin alpha- and beta-subunit promoters
      by AP-2.
AB  - Production of the placental hormone, chorionic gonadotropin (CG), increases
      dramatically as cytotrophoblasts fuse to form syncytiotrophoblasts. The CG alpha-
      and beta-promoters are both responsive to cAMP, although the kinetics of cAMP
      stimulation are different. In an effort to understand the mechanisms of
      coordinate induction of these genes, AP-2 binding sites were identified in the
      promoter regions of the alpha and CGbeta genes. AP-2 bound to the upstream
      regulatory element (-186 to -156 base pairs (bp)) in the alpha-promoter and to
      several different regions of the CGbeta promoter, including footprints 2 and 4B
      (FP2, -311 to -279 bp; FP4B, 221 to -200 bp). AP-2 antibodies induced supershifts
      of these complexes, confirming the identity of the protein-DNA complex. In JEG-3
      cells, which contain abundant AP-2, mutations in these CGbeta AP-2 sites reduced
      basal activity and decreased cAMP stimulation. In AP-2-deficient Hep-G2 cells, co
      transfection of AP-2 stimulated expression of the CGbeta promoter 10-20-fold, and
      the alpha-promoter was induced by 3-6-fold. Mutations that eliminate AP-2 binding
      to CGbeta FP4B reduced AP-2 stimulation by more than 80%, whereas mutations in
      FP2 reduced AP-2 stimulation by less than 50%. Analyses of AP-2 mutants revealed
      a requirement for the DNA binding/dimerization domain and the amino-terminal
      proline-rich and acid-rich transactivation domains for stimulation of the CGbeta
      promoter. Primary cultures of placental cytotrophoblasts were differentiated into
      syncytiotrophoblasts in vitro to examine AP-2 expression by reverse transcriptase
      polymerase chain reaction. AP-2 mRNA levels increased by day 2 and continued to
      rise in parallel with a marked increase in alpha and CGbeta gene expression. We
      conclude that both the alpha and CGbeta promoters contain binding sites for AP-2
      and suggest that this transcription factor provides a mechanism for coordinating
      the induction of these genes during placental cell differentiation.

PMID- 9182572
TI  - Eps15 is constitutively oligomerized due to homophilic interaction of its coiled
      coil region.
AB  - Eps15 is a member of an emerging family of proteins containing a novel
      protein/protein interaction domain, the EH domain, of as yet unknown function.
      Recent findings of Eps15 association with clathrin adaptor complex AP-2 and its
      localization in clathrin-coated pits have implicated Eps15 in the regulation of
      vesicle trafficking. Here we show that Eps15 exists in several multimeric states
      in vivo. When purified recombinant Eps15 or lysates of NIH 3T3 cells were treated
      with cross-linking reagents, covalent dimers of Eps15 and larger covalent
      multimers were detected in high yield. Large Eps15 oligomers co
      immunoprecipitated with AP-2 at an efficiency higher than that of Eps15 dimers.
      Furthermore, cross-linking of the membrane-bound fraction of Eps15 in mildly
      permeabilized cells was as efficient as that of the cytosolic fraction. Size
      exclusion column chromatography of recombinantly produced Eps15 and of total cell
      lysates was performed to examine the equilibrium ratio of the monomers versus the
      aggregated forms of Eps15. These experiments showed that essentially all the
      Eps15 was aggregated, whereas monomers of Eps15 could be obtained only under
      strong denaturing conditions. To map the region of Eps15 responsible for
      dimerization, fusion proteins corresponding to the three structural domains of
      Eps15 were prepared. Cross-linking analysis revealed that the central portion of
      Eps15, which possesses a coiled-coil region (residues 321-520), serves as the
      interacting interface. The possibility that hetero-oligomeric complexes of Eps15
      dimers and AP-2 function during the recruitment of proteins into coated pits is
      discussed.

PMID- 9182573
TI  - Calmodulin modulates the interaction between IQGAP1 and Cdc42. Identification of
      IQGAP1 by nanoelectrospray tandem mass spectrometry.
AB  - Calmodulin regulates numerous fundamental metabolic pathways by binding to and
      modulating diverse target proteins. In this study, calmodulin-binding proteins
      were isolated from normal (Hs578Bst) and malignant (MCF-7) human breast cell
      lines with calmodulin-Sepharose and analyzed by SDS-polyacrylamide gel
      electrophoresis. A protein that migrated at approximately 190 kDa bound to
      calmodulin in the presence of Ca2+ and was the only calmodulin-binding protein
      detected in the absence of Ca2+. This 190-kDa protein was identified as IQGAP1 by
      nanoelectrospray mass spectrometry and collision-induced dissociation tandem mass
      spectrometry. IQGAP1 coimmunoprecipitated with calmodulin from lysates of MCF-7
      cells. Moreover, overlay with 125I-calmodulin confirmed that IQGAP1 binds
      directly to calmodulin. Analysis of the functional effects of the interaction
      revealed that Ca2+/calmodulin disrupted the binding of purified IQGAP1 to the Ras
      related protein Cdc42 in a concentration-dependent manner. These data clearly
      identify IQGAP1 as the predominant calmodulin-binding protein in Ca2+-free breast
      cell lysates and reveal that calmodulin modulates the interaction between IQGAP1
      and Cdc42.

PMID- 9182574
TI  - A role for protein kinase CbetaI in the regulation of Ca2+ entry in Jurkat T
      cells.
AB  - T cell activation leading to cytokine production and cellular proliferation
      involves a regulated increase and subsequent decrease in the intracellular
      concentration of Ca2+ ([Ca2+]i). While much is understood about agonist-induced
      increases in [Ca2+]i, less is known about down-regulation of this pathway.
      Understanding the mechanism of this down-regulation is critical to the prevention
      of cell death that can be the consequence of a sustained elevation in [Ca2+]i.
      Protein kinase C (PKC), activated by the diacylglycerol produced as a consequence
      of T cell receptor engagement, has long been presumed to be involved in this down
      regulation, although the precise mechanism is not wholly clear. In this report we
      demonstrate that activation of PKC by phorbol esters slightly decreases the rate
      of Ca2+ efflux from the cytosol of Jurkat T cells following stimulation through
      the T cell receptor or stimulation in a receptor-independent manner by
      thapsigargin. On the other hand, phorbol ester treatment dramatically reduces the
      rate of Ca2+ influx following stimulation. Phorbol ester treatment is without an
      effect on Ca2+ influx in a different T cell line, HSB. Down-regulation of
      PKCbetaI expression by 18-h phorbol ester treatment is associated with a loss of
      the response to acute phorbol ester treatment in Jurkat cells, suggesting that
      PKCbetaI may be the isozyme responsible for the effects on Ca2+ influx.
      Electroporation of an anti-PKCbetaI antibody, but not antibodies against PKCalpha
      or PKCgamma, led to an increase in the rate of Ca2+ influx following stimulation.
      Taken together, these data suggest that PKCbetaI may be a component of the down
      regulation of increases in [Ca2+]i associated with Jurkat T cell activation.

PMID- 9182575
TI  - A new family of 10 murine ovalbumin serpins includes two homologs of proteinase
      inhibitor 8 and two homologs of the granzyme B inhibitor (proteinase inhibitor
      9).
AB  - Serine proteinase inhibitors (serpins) are classically regulators of
      extracellular proteolysis, however, recent evidence suggests that some function
      intracellularly. Such "ovalbumin" serpins include the human proteinase inhibitors
      6 (PI-6), 8 (PI-8), and 9 (PI-9), plasminogen activator inhibitor 2, and the
      monocyte/neutrophil elastase inhibitor. PI-9 is a potent granzyme B (graB)
      inhibitor that has an unusual P1 Glu and is present primarily in lymphocytes. In
      a search for the murine equivalent of PI-9 we screened cDNA libraries, and
      performed reverse transcriptase-polymerase chain reaction on RNA isolated from
      leukocyte cell lines and from lymph nodes and spleens of allo-immunized mice. We
      identified 10 new ovalbumin serpin sequences: two resemble PI-8, two resemble PI
      9, and the remaining six have no obvious human counterparts. By RNA analysis only
      one of the two sequences resembling PI-9 (designated SPI6) is present in mouse
      lymphocytes while the other (a partial clone designated mBM2A) is predominantly
      in testis. SPI6 comprises a 1.8-kilobase cDNA encoding a 374-amino acid
      polypeptide that is 68% identical to PI-9. mBM2A is 65% identical to PI-9 and
      over 80% identical to SPI6. Although the reactive loops of SPI6 and mBM2A differ
      from PI-9, both contain a Glu in a region likely to contain the P1-P1' bond. SPI6
      produced in vitro using a coupled transcription/translation system formed an SDS
      stable complex with human graB and did not interact with trypsin, chymotrypsin,
      leukocyte elastase, pancreatic elastase, thrombin, or cathepsin G. Recombinant
      SPI6 produced in a yeast expression system was used to examine the interaction
      with human graB in more detail. The second-order rate constant for the
      interaction was estimated as 8 x 10(4) M-1 s-1, and inhibition depended on the
      Glu in the SPI6 reactive center. The SPI6 gene was mapped to the same region on
      mouse chromosome 13 as Spi3, which encodes the murine homolog of PI-6. We
      conclude that even though their reactive centers are not highly conserved, SPI6
      is a functional homolog of PI-9, and that the regulation of graB in the mouse may
      involve a second serpin encoded by mBM2A. Our identification of multiple sequence
      homologs of PI-8 and PI-9, and six new ovalbumin serpins, is consonant with the
      idea that the larger set of granule and other proteinases known to exist in the
      mouse (compared with human) is balanced by a larger array of serpins.

PMID- 9182576
TI  - Vascular endothelial growth factor stimulates tyrosine phosphorylation and
      recruitment to new focal adhesions of focal adhesion kinase and paxillin in
      endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) stimulated the tyrosine phosphorylation
      of multiple components in confluent human umbilical vein endothelial cells
      (HUVECs) including bands of Mr 205,000, corresponding to the VEGF receptors Flt-1
      and KDR, and Mr 145,000, 120,000, 97,000, and 65,000-70,000. VEGF caused a
      striking and transient increase in mitogen-activated protein (MAP) kinase
      activity and stimulated phospholipase C-gamma tyrosine phosphorylation, but it
      had no effect on phosphatidylinositol 3'-kinase activity. VEGF caused a marked
      increase in tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK)),
      which was both rapid and concentration-dependent. VEGF produced similar effects
      on p125(FAK) in the endothelial cell line ECV.304. VEGF stimulated tyrosine
      phosphorylation of the 68-kDa focal adhesion-associated component, paxillin, with
      similar kinetics and concentration dependence to that for p125(FAK). Thrombin and
      the phorbol ester, phorbol 12-myristate 13-acetate, also increased p125(FAK)
      tyrosine phosphorylation in HUVECs. The effect of VEGF on p125(FAK) tyrosine
      phosphorylation was completely inhibited by the actin filament-disrupting agent
      cytochalasin D and was partially inhibited by the protein kinase C inhibitor
      GF109203X. Inhibition of the MAP kinase pathway using a specific inhibitor of MAP
      kinase kinase had no effect on p125(FAK) tyrosine phosphorylation. VEGF
      stimulated migration and actin stress fiber formation in confluent HUVEC, and
      VEGF-induced p125(FAK)/paxillin tyrosine phosphorylation was accompanied by
      increased immunofluorescent staining of p125(FAK), paxillin, and phosphotyrosine
      in focal adhesions in confluent cultures of HUVECs. These findings identify
      p125(FAK) and paxillin as components in a VEGF-stimulated signaling pathway and
      suggest a novel mechanism for VEGF regulation of endothelial cell functions.

PMID- 9182577
TI  - Effects of mutating specific residues present near the amino terminus of 2'-5'
      oligoadenylate synthetase.
AB  - In this study, we investigated the role of specific amino acid residues present
      near the amino terminus of the 9-2 isozyme of 2'-5'-oligoadenylate synthetase. In
      vitro expression of deletion mutants showed that residues 1-9 are required for
      enzyme activity. Within this region, residues 3, 7, and 8 were found to be
      conserved among all known isozymes of 2'-5'-oligoadenylate synthetase. Mutation
      of these residues singly or in combination resulted in partial or total loss of
      enzyme activity. Substitution of the proline residue at position 7 by different
      residues caused a partial or complete loss of activity. The properties of the
      inactive P7Q mutant were further explored by expressing the protein in bacteria.
      The bacterially expressed protein was also enzymatically inactive. The mutant
      protein could bind the substrate ATP and the activator double-stranded RNA
      normally. Oligomerization properties of the protein were examined by an affinity
      based interaction assay and by glycerol gradient centrifugation; there was no
      detectable difference between the wild type and the P7Q mutant. These results
      demonstrated the importance of the proline residue at position 7 in conferring
      enzyme activity to the protein without affecting its other properties.

PMID- 9182578
TI  - Two discrete regions of interleukin-2 (IL2) receptor beta independently mediate
      IL2 activation of a PD98059/rapamycin/wortmannin-insensitive Stat5a/b serine
      kinase.
AB  - Many cytokines, hormones, and growth factors activate Janus kinases to tyrosine
      phosphorylate select members of the Stat transcription factors. For full
      transcriptional activation, Stat1 and Stat3 also require phosphorylation of a
      conserved serine residue within a mitogen-activated protein kinase
      phosphorylation consensus site. On the other hand, two recently identified and
      highly homologous Stat5a and Stat5b proteins lack this putative mitogen-activated
      protein kinase phosphorylation site. The present study set out to establish
      whether Stat5a and Stat5b are under the control of an interleukin-2 (IL2)
      activated Stat5 serine kinase. We now report that IL2 stimulated marked
      phosphorylation of serine and tyrosine residues of both Stat5a and Stat5b in
      human T lymphocytes and in several IL2-responsive lymphocytic cell lines. No
      Stat5a/b phosphothreonine was detected. Phosphoamino acid analysis also revealed
      that Stat5a/b phosphotyrosine levels were maximized within 1-5 min of IL2
      stimulation, whereas serine phosphorylation kinetics were slower. Interestingly,
      IL2-induced serine phosphorylation of Stat5a differed quantitatively and
      temporally from that of Stat5b with Stat5a serine phosphorylation leveling off
      after 10 min and the more pronounced Stat5b response continuing to rise for at
      least 60 min of IL2 stimulation. Furthermore, we identified two discrete domains
      of IL2 receptor beta (IL2Rbeta) that could independently restore the ability of a
      truncated IL2Rbeta mutant to mediate Stat5a/b phosphorylation and DNA binding to
      the gamma-activated site of the beta-casein gene promoter. These observations
      demonstrated that there is no strict requirement for one particular IL2Rbeta
      region for Stat5 phosphorylation. Finally, we established that the IL2-activated
      Stat5a/b serine kinase is insensitive to several selective inhibitors of known
      IL2-stimulated kinases including MEK1/MEK2 (PD98059), mTOR (rapamycin), and
      phosphatidylinositol 3-kinase (wortmannin) as determined by phosphoamino acid and
      DNA binding analysis, thus suggesting that a yet-to-be-identified serine kinase
      mediates Stat5a/b activation.

PMID- 9182579
TI  - The 3'-untranslated region of the alpha2C-adrenergic receptor mRNA impedes
      translation of the receptor message.
AB  - We report that two subtypes of alpha2-adrenergic receptors (alpha2A/D- and
      alpha2C-AR) are ectopically expressed with dramatically different efficiencies
      and that this difference is due to a 288-nucleotide (nt) segment in the 3'
      untranslated region (3'-UTR) of the alpha2C-AR mRNA that impairs translational
      processing. NIH-3T3 fibroblasts were transfected with receptor constructs (coding
      region plus 552 nt, alpha2C-AR; coding region plus 1140 nt, alpha2A/D-AR) and a
      vector conferring G418 resistance. Transcription was driven by the murine sarcoma
      virus promoter element, and the receptor gene segment was upstream of an SV40
      polyadenylation cassette. Drug-resistant transfectants were evaluated for
      expression of receptor mRNA and protein. 90% of the NIH-3T3 alpha2C-AR
      transfectants expressed receptor mRNA, but only 14% of the clonal cell lines
      expressed receptor protein. In contrast, 90% of the NIH-3T3 alpha2A/D-AR
      transfectants expressed receptor protein (200-5000 fmol/mg). Similar results were
      obtained following transfection of DDT1MF-2 cells with the two receptor
      constructs. The role of the 3'-UTR of the alpha2C-AR in mRNA processing was
      determined by generating new constructs in which the 3'-UTR was progressively
      truncated from 552 to 470, 182, 143, or 74 nt 3' to the stop codon. Truncation of
      the 3'-UTR resulted in the expression of receptor protein in the G418-resistant
      transfectants (nt 74, 100%; nt 143, 80%; nt 182, 50%). The level of mRNA in the
      transfectants expressing the receptor protein was not greater than that in
      nonexpressing clones, and the differences in protein expression did not reflect
      altered mRNA stability in the truncated construct. The alpha2C-AR mRNA with the
      longer 3'-UTR underwent translational initiation as it was found in the polysome
      fraction, indicating that the lack of receptor protein was due to impaired
      translational elongation or termination. These data suggest that translational
      efficiency is a key mechanism for regulating alpha2C-AR expression and associated
      signaling events.

PMID- 9182580
TI  - A mitogenic action for fibrinogen mediated through intercellular adhesion
      molecule-1.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a cell surface ligand for
      alphaLbeta2 and alphaMbeta2 integrins and has a key role in leukocyte adhesion to
      the vascular endothelium. The plasma protein fibrinogen has also been shown to
      interact with ICAM-1. We have investigated the effect of fibrinogen binding to
      ICAM-1-expressing cells on cell proliferation. The inclusion of 200-800 nM
      fibrinogen but not fibronectin to the culture medium of Raji induced a 2-4-fold
      increase in [3H]thymidine incorporation after 8 h. Cell proliferation in cultures
      containing fibrinogen was also confirmed by direct cell counting. The
      proliferative response in Raji was abrogated by an anti-ICAM-1 mAb 84H10 which
      maps to the first Ig domain of ICAM-1. A purified truncated form of ICAM-1
      containing the first two Ig-like domains and a peptide with amino acid sequence
      corresponding to ICAM-1 (8-22) was also able to block the proliferative action of
      fibrinogen on Raji. 200 nM fibrinogen induced a 3-fold increase in [3H]thymidine
      incorporation by 293 cells transfected with ICAM-1 cDNA but not control non
      transfected 293 cells. Comparable mitogenic effects were achieved with fibrinogen
      fragments X and D100, and with a synthetic peptide with an amino acid sequence
      matching fibrinogen gamma chain (117-133). These results indicate that
      interaction between discrete sequences within ICAM-1 and fibrinogen result in
      cellular proliferation.

PMID- 9182581
TI  - A truncated form of RGS3 negatively regulates G protein-coupled receptor
      stimulation of adenylyl cyclase and phosphoinositide phospholipase C.
AB  - Identification of a new family of proteins (RGS proteins) that function as
      negative regulators of G protein signaling has sparked new understanding of
      desensitization of this signaling process. Recent studies with several mammalian
      RGS proteins has delineated their ability to interact with and function as GTPase
      activating proteins specifically for G proteins in the Gi family. Here, we
      investigated the functional activity of RGS3 and a truncated form of RGS3 on G
      protein-coupled receptor-mediated activation of adenylyl cyclase,
      phosphoinositide phospholipase C, and mitogen-activated protein kinase in intact
      cells. Polymerase chain reaction and 5'-rapid amplification of cDNA ends analyses
      revealed the tissue-specific expression of a short form of the RGS3 transcript
      that encodes the approximate carboxyl-terminal half of RGS3. This truncated form
      of RGS3 (RGS3T) was shown recently to function as a negative regulator of
      pheromone signaling in yeast (Druey, K. M., Blumer, K. J., Kang, V. R., and
      Kehrl, J. H. (1996) Nature 379, 742-746). Baby hamster kidney cells transiently
      transfected with RGS3T cDNA exhibited a pronounced impairment in platelet
      activating factor receptor-stimulated inositol phosphate production, a pertussis
      toxin-insensitive response. Similarly, calcitonin gene-related peptide receptor
      stimulated increases in intracellular cAMP and pituitary adenylate-cyclase
      activating polypeptide receptor-stimulated increases in both cAMP and inositol
      phosphates were reduced significantly in RGS3T transfectants compared with vector
      transfected control cells. In contrast, baby hamster kidney cells transfected
      with the full-length RGS3 cDNA showed no impairment in cAMP and inositol
      phosphate production mediated by these G protein-coupled receptors. However,
      lysophosphatidic acid receptor-stimulated phosphorylation of endogenous ERK1 and
      ERK2 was impaired markedly in both RGS3 and RGS3T transfectants, demonstrating
      the functional ability of both RGS forms to modulate Gi-mediated signaling. These
      results provide the first evidence for regulatory effects of an RGS protein on Gs
      and Gq-mediated signaling in intact cells and document that the carboxyl
      terminal region of RGS3 comprises the structural domain for this activity.

PMID- 9182582
TI  - A recombinant protein of two high molecular weight glutenins alters gluten
      polymer formation in transgenic wheat.
AB  - Wheat high molecular weight glutenin subunits (HMW-GS) are the most important
      determinants of its superiority for making leavened bread. Following synthesis,
      these proteins are sequestered into the endoplasmic reticulum and assemble into
      extremely large elastic polymers, linked by noncovalent and intermolecular
      disulfide bonds. To study the structural requirements for the assembly of HMW-GS,
      we have expressed in transgenic wheat a recombinant protein between two cognate x
      and y-type subunits. In contrast to the natural polymerized x- and y-type HMW
      GS, a significant amount of the recombinant subunit remained monomeric.
      Nonreducing SDS-polyacrylamide gel electrophoresis, coupled with limited
      proteolysis, showed that the monomeric form of the recombinant subunit contained
      an unusual intramolecular disulfide bond, linking an N-terminal cysteine to the
      single C-terminal cysteine residue. In addition, sucrose gradient analysis
      revealed that this intramolecular disulfide bond impeded the ability of the
      recombinant subunit to assemble into polymers. Despite of its altered assembly, a
      notable amount of the overexpressed recombinant subunit was also present in
      glutenin polymers. Moreover, its presence significantly altered the subunit
      composition of the polymer. Our results show that it is possible to modify gluten
      assembly and properties by expressing recombinant HMW-GS in transgenic wheat, and
      have a major implication for the improvement of wheat bread-making quality.

PMID- 9182583
TI  - Specific, high affinity binding of tissue inhibitor of metalloproteinases-4 (TIMP
      4) to the COOH-terminal hemopexin-like domain of human gelatinase A. TIMP-4 binds
      progelatinase A and the COOH-terminal domain in a similar manner to TIMP-2.
AB  - The binding properties of the newly described tissue inhibitor of
      metalloproteinases-4 (TIMP-4) to progelatinase A and to the COOH-terminal
      hemopexin-like domain (C domain) of the enzyme were examined. We present evidence
      for the first time of a specific, high affinity interaction between TIMP-4 and
      the C domain of human gelatinase A and show that TIMP-4 binds both progelatinase
      A and the C domain in a similar manner to that of TIMP-2. Saturable binding of
      recombinant C domain to TIMP-4 and to TIMP-2 but not to TIMP-1 was demonstrated
      using a microwell protein binding assay. The recombinant collagen binding domain
      of gelatinase A, comprised of the three fibronectin type II-like repeats, did not
      bind to TIMP-4, indicating that binding is mediated selectively by the C domain.
      Binding to TIMP-4 was of high affinity with an apparent Kd of 1.7 x 10(-7) M but
      slightly weaker than that to TIMP-2 (apparent Kd of 0.66 x 10(-7) M). Affinity
      chromatography confirmed the TIMP-4-C domain interaction and also showed that the
      complex could not be disrupted by 1 M NaCl or 10% dimethyl sulfoxide, thereby
      further demonstrating the tight binding. To verify the biological significance of
      this interaction, binding of full-length progelatinase A to TIMP-4 was
      investigated. TIMP-4 and TIMP-2 but not TIMP-1 bound specifically to purified
      TIMP-2-free human recombinant full-length progelatinase A and to full-length rat
      proenzyme from the conditioned culture medium of ROS 17/2.8 cells. Preincubation
      of the C domain with TIMP-2 was found to reduce subsequent binding to TIMP-4 in a
      concentration-dependent manner. Competition between TIMP-2 and TIMP-4 for a
      common or overlapping binding sites on the gelatinase A C domain may occur;
      alternatively TIMP-2 may prevent the binding of TIMP-4 by steric hindrance or
      induction of a conformational change in the C domain. We propose that the binding
      of progelatinase A to TIMP-4 represents a third TIMP-progelatinase interaction in
      addition to that of progelatinase A with TIMP-2 and progelatinase B with TIMP-1
      described previously. This new phenomenon may be of important physiological
      significance in modulating the cell surface activation of progelatinase A.

PMID- 9182584
TI  - The fibrinogen-like globe of tenascin-C mediates its interactions with neurocan
      and phosphacan/protein-tyrosine phosphatase-zeta/beta.
AB  - Two nervous tissue-specific chondroitin sulfate proteoglycans, neurocan and
      phosphacan (the extracellular domain of protein-tyrosine phosphatase-zeta/beta),
      are high-affinity ligands of tenascin-C. Using portions of tenascin-C expressed
      as recombinant proteins in human fibrosarcoma cells, we have demonstrated both by
      direct radioligand binding assays and inhibition studies that phosphacan binding
      is retained in all deletion variants except those lacking the fibrinogen-like
      globe and that phosphacan binds to this single domain with nearly the same
      affinity (Kd approximately 12 nM) as to native or recombinant tenascin-C.
      However, maximum binding of neurocan requires both the fibrinogen globe and some
      of the adjacent fibronectin type III repeats. Binding of phosphacan and neurocan
      to intact tenascin-C, and of phosphacan to the fibrinogen globe, is significantly
      increased in the presence of calcium. Chondroitinase treatment of the
      proteoglycans did not affect their binding to either native tenascin-C or to any
      of the recombinant proteins, demonstrating that these interactions are mediated
      by the proteoglycan core proteins rather than through the glycosaminoglycan
      chains. These results are also consistent with rotary shadowing electron
      micrographs that show phosphacan as a rod terminated at one end by a globular
      domain that is frequently seen apposed to the fibrinogen globe in mixtures of
      phosphacan and tenascin-C. C6 glioma cells adhere to and spread on deletion
      variants of tenascin-C containing only the epidermal growth factor-like domains
      or the fibronectin type III repeats and the fibrinogen globe. In both cases cell
      adhesion was inhibited by similar concentrations of phosphacan, demonstrating
      that the fibrinogen globe is not necessary for this effect, which is apparently
      mediated by a direct action of phosphacan on the cells rather than by its
      interaction with the proteoglycan binding site on tenascin-C.

PMID- 9182585
TI  - Isolation of mitochondrial DNA-less mouse cell lines and their application for
      trapping mouse synaptosomal mitochondrial DNA with deletion mutations.
AB  - For isolation of mouse mtDNA-less (rho0) cell lines, we searched for various
      antimitochondrial drugs that were expected to decrease the mtDNA content and
      found that treatment with ditercalinium, an antitumor bis-intercalating agent,
      was extremely effective for completely excluding mtDNA in all the mouse cell
      lines we tested. The resulting rho0 mouse cells were successfully used for
      trapping the mtDNA of living nerve cells into dividing cultured cells by fusion
      of the rho0 cells with mouse brain synaptosomes, which represent synaptic endings
      isolated from nerve cells. With neuronal mtDNA obtained, all of the cybrid clones
      restored mitochondrial translation activity similarly regardless of whether the
      mtDNA was derived from young or aged mice, thus at least suggesting that defects
      in mitochondrial genomes are not involved in the age-associated mitochondrial
      dysfunction observed in the brain of aged mice. Furthermore, we could trap a very
      small amount of a common 5823-base pair deletion mutant mtDNA (DeltamtDNA5823)
      that was detectable by polymerase chain reaction in the cybrid clones. As the
      amount of mutant mtDNA with large scale deletions was expected to increase during
      prolonged cultivation of the cybrids, these cells should be available for
      establishment of mice containing the deletion mutant mtDNA.

PMID- 9182586
TI  - Processing of the rne transcript by an RNase E-independent amino acid-dependent
      mechanism.
AB  - RNase E is encoded by the rne (also known as ams or hmp) gene and is the
      principal enzyme that controls the chemical decay of bulk mRNA in Escherichia
      coli. Earlier work has shown that RNase E degrades its own mRNA, autoregulating
      production of the RNase E protein. Here we show that in cells lacking RNase E
      activity, the 3.6-kilobase rne gene transcript is cleaved site specifically at
      two locations near its center by a novel endonuclease whose activity is modulated
      by the presence or absence of amino acids in the culture medium. These cleavages
      produce a 2-kilobase RNase E-sensitive RNA fragment corresponding to the 3' half
      of the transcript. Using primer extension and RNase protection analysis, we
      mapped RNase E-independent cleavages to sites 1558 and 1576 nucleotides from the
      5' end of the rne transcript (coordinates 1738 and 1747 of the rne gene). Our
      results indicate the existence of a previously unknown RNase E-independent
      mechanism for degradation of rne transcripts and further demonstrate that this
      mechanism responds to changes in cell growth conditions.

PMID- 9182587
TI  - In vitro recognition of specific DNA targets by AlcR, a zinc binuclear cluster
      activator different from the other proteins of this class.
AB  - AlcR is the transactivator mediating transcriptional induction of the alc gene
      cluster in Aspergillus nidulans. The AlcR DNA-binding domain consists of a zinc
      binuclear cluster different from the other members of the Zn2Cys6 family by
      several features. In particular, it is able to bind to symmetric and asymmetric
      sites with the same affinity, with both sites being functional in A. nidulans.
      Here, we show that unlike the other proteins of the Zn2Cys6 binuclear cluster
      family, AlcR binds most probably as a monomer to its cognate targets. Two
      molecules of the AlcR protein can simultaneously bind in a noncooperative manner
      to inverted repeats. The consensus core has been determined precisely (5'-CCGCN
      3'), and the AlcR-binding site in the aldA promoter has been localized. The
      sequence downstream of the zinc cluster is necessary for high affinity binding.
      Furthermore, our data show that the use of the carrier protein glutathione S
      transferase in AlcR binding experiments introduces an important bias in the
      recognition of DNA sites due to its tertiary dimeric structure.

PMID- 9182588
TI  - The Ktr1p, Ktr3p, and Kre2p/Mnt1p mannosyltransferases participate in the
      elaboration of yeast O- and N-linked carbohydrate chains.
AB  - We have determined a role for Ktr1p and Ktr3p as mannosyltransferases in the
      synthesis of the carbohydrate chains attached to Saccharomyces cerevisiae O- and
      N-modified proteins. KTR1 and KTR3 encode related proteins that are highly
      similar to the Kre2p/Mnt1p Golgi alpha1,2-mannosyltransferase (Lussier, M.,
      Camirand, A., Sdicu, A.-M., and Bussey, H. (1993) Yeast 9, 1057-1063; Mallet, L.,
      Bussereau, F., and Jacquet, M. (1994) Yeast 10, 819-831). Examination of the
      electrophoretic mobility of a specifically O-linked protein from mutants and an
      analysis of their total O-linked mannosyl chains demonstrates that Ktr1p, Ktr3p,
      and Kre2p/Mnt1p have overlapping roles and collectively add most of the second
      and the third alpha1,2-linked mannose residues on O-linked oligosaccharides.
      Determination of the mobility of the specifically N-linked glycoprotein invertase
      in different null strains indicates that Ktr1p, Ktr3p, and Kre2p are also jointly
      involved in N-linked glycosylation, possibly in establishing some of the outer
      chain alpha1,2-linkages.

PMID- 9182589
TI  - Substitution of the seat-belt region of the thyroid-stimulating hormone (TSH)
      beta-subunit with the corresponding regions of choriogonadotropin or follitropin
      confers luteotropic but not follitropic activity to chimeric TSH.
AB  - The region between the 10th and 12th cysteine (Cys88-Cys105 in human thyroid
      stimulating hormone beta-subunit (hTSHbeta)) of the glycoprotein hormone beta
      subunits corresponds to the disulfide-linked seat-belt region. It wraps around
      the common alpha-subunit and has been implicated in regulating specificity
      between human choriogonadotropin (hCG) and human follicle-stimulating hormone
      (hFSH), but determinants of hTSH specificity are unknown. To characterize the
      role of this region for hTSH, we constructed hTSH chimeras in which the entire
      seat-belt region Cys88-Cys105 or individual intercysteine segments Cys88-Cys95
      and Cys95-Cys105 were replaced with the corresponding sequences of hCG and hFSH
      or alanine cassettes. Alanine cassette mutagenesis of hTSH showed that the Cys95
      Cys105 segment of the seat-belt was more important for TSH receptor binding and
      signal transduction than the Cys88-Cys95 determinant loop region. Replacing the
      entire seat-belt of hTSHbeta with the hCG sequence conferred full hCG receptor
      binding and activation to the hTSH chimera, whereas TSH receptor binding and
      activation were abolished. Conversely, introduction of the hTSHbeta seat-belt
      sequence into hCGbeta generated an hCG chimera that bound to and activated the
      TSH receptor but not the CG/lutropin (LH) receptor. In contrast, an hTSH chimera
      bearing hFSH seat-belt residues did not possess any follitropic activity, and its
      thyrotropic activity was only slightly reduced. This may in part be due to the
      fact that the net charge of the seat-belt is similar in hTSH and hFSH but
      different from hCG. However, exchanging other regions of charge heterogeneity
      between hTSHbeta and hFSHbeta did not confer follitropic activity to hTSH. Thus,
      exchanging the seat-belt region between hTSH and hCG switches hormonal
      specificity in a mutually exclusive fashion. In contrast, the seat-belt appears
      not to discriminate between the TSH and the FSH receptors, indicating for the
      first time that domains outside the seat-belt region contribute to glycoprotein
      hormone specificity.

PMID- 9182590
TI  - Protein kinase C-mediated phosphorylation and functional regulation of dopamine
      transporters in striatal synaptosomes.
AB  - Dopamine transporters (DATs) are members of a family of Na+- and Cl--dependent
      neurotransmitter transporters responsible for the rapid clearance of dopamine
      from synaptic clefts. The predicted primary sequence of DAT contains numerous
      consensus phosphorylation sites. In this report we demonstrate that DATs undergo
      endogenous phosphorylation in striatal synaptosomes that is regulated by
      activators of protein kinase C. Rat striatal synaptosomes were metabolically
      labeled with [32P]orthophosphate, and solubilized homogenates were subjected to
      immunoprecipitation with an antiserum specific for DAT. Basal phosphorylation
      occurred in the absence of exogenous treatments, and the phosphorylation level
      was rapidly increased when synaptosomes were treated with the phosphatase
      inhibitors okadaic acid or calyculin. Treatment of synaptosomes with the protein
      kinase C activator phorbol 12-myristate 13-acetate (PMA) also increased the level
      of phosphate incorporation. This occurred within 10 min and was dosedependent
      between 0.1 and 1 microM PMA. DAT phosphorylation was also significantly
      increased by two other protein kinase C activators, (-)-indolactam V and 1-oleoyl
      2-acetyl-sn-glycerol. The inactive phorbol ester 4alpha-phorbol 12,13-didecanoate
      at 10 microM was without effect, and PMA-induced phosphorylation was blocked by
      treatment of synaptosomes with the protein kinase C inhibitors staurosporine and
      bisindoylmaleimide. These results indicate that DATs undergo rapid in vivo
      phosphorylation in response to protein kinase C activation and that a robust
      mechanism exists in synaptosomes for DAT dephosphorylation. Dopamine transport
      activity in synaptosomes was reduced by all treatments that promoted DAT
      phosphorylation, with comparable dose, time, and inhibitor characteristics. The
      change in transport activity was produced by a reduction in Vmax with no
      significant effect on the Km for dopamine. These results suggest that
      synaptosomal dopamine transport activity is regulated by phosphorylation of DAT
      and present a potential mechanism for local neuronal control of synaptic
      neurotransmitter levels and consequent downstream neural activity.

PMID- 9182591
TI  - Modulation of cell death in yeast by the Bcl-2 family of proteins.
AB  - Bcl-2 family members are regulators of cell death. The precise biochemical
      properties of these proteins are unclear although intrafamily protein-protein
      association is thought to be involved. To elucidate structure-activity
      relationships among Bcl-2 proteins and identify the pathways in which they act,
      an inducible death suppressor assay was developed in yeast. Only Bax and Bak
      killed yeast via a process that did not require interleukin-1beta-converting
      enzyme-like proteases. Bax/Bak lethality was suppressed by coexpression of Bcl-2
      family members that are anti-apoptotic in vertebrates, namely Bcl-xL, Bcl-2, Mcl
      1, and A1. Furthermore, Bcl-xL and Bcl-2 suppressed Bax toxicity by distinct
      mechanisms in yeast. Bad, Bcl-xS, and Ced-9 lacked suppressor activity. These
      inactive proteins bound to anti-apoptotic members of the Bcl-2 family but not to
      Bax or Bak. In contrast, most Bcl-2 family proteins that attenuated death bound
      to Bax and Bak. However, two mutants of Bcl-xL suppressed Bax-induced cell death
      while having no Bax binding activity. Therefore, Bcl-xL functions independently
      of Bax binding, perhaps by interacting with a common target or promoting a
      pathway that antagonizes Bax. Thus, the pathways downstream of Bax and Bcl-xL may
      be conserved between vertebrates and yeast. This suppressor assay could be used
      to isolate components of these pathways.

PMID- 9182592
TI  - Expression and purification of the Saccharomyces cerevisiae alpha-factor receptor
      (Ste2p), a 7-transmembrane-segment G protein-coupled receptor.
AB  - A plasmid vector was developed that permitted high-level expression of a
      functional form of the Saccharomyces cerevisiae alpha-factor receptor (the STE2
      gene product) tagged at its C-terminal end with an epitope (FLAG) and a His6
      tract. When expressed in yeast from this plasmid, Ste2p was produced at a level
      at least 3-fold higher than that reported previously for any other 7
      transmembrane-segment receptor expressed in the same cells. For purification,
      isolated cell membranes containing the overexpressed receptor were solubilized
      with detergent under specific conditions and subjected to immobilized metal
      affinity chromatography. Yields as high as 1 mg of nearly homogeneous (95%)
      receptor were routinely obtained even from relatively small scale preparations
      (60 g of frozen cell paste). The purified receptor was reconstituted into
      artificial phospholipid vesicles. Radioligand binding studies demonstrated that
      the purified receptor, in the reconstituted vesicles, bound its tridecapeptide
      ligand (alpha-factor) with a KD (155 nM) consistent with the affinity expected
      for this receptor in the absence of its associated G protein. Efficient
      restoration of ligand binding activity upon reconstitution required the addition
      of solubilized membranes prepared from a yeast strain lacking the receptor.
      Sufficient amounts of active material can be obtained by this procedure to allow
      physical studies of this receptor and other 7-transmembrane-segment receptors
      expressed in this system.

PMID- 9182593
TI  - Proteolytic activation of cholera toxin and Escherichia coli labile toxin by
      entry into host epithelial cells. Signal transduction by a protease-resistant
      toxin variant.
AB  - Cholera and Escherichia coli heat-labile toxins (CT and LT) require proteolysis
      of a peptide loop connecting two major domains of their enzymatic A subunits for
      maximal activity (termed "nicking"). To test whether host intestinal epithelial
      cells may supply the necessary protease, recombinant rCT and rLT and a protease
      resistant mutant CTR192H were prepared. Toxin action was assessed as a Cl-
      secretory response (Isc) elicited from monolayers of polarized human epithelial
      T84 cells. When applied to apical cell surfaces, wild type toxins elicited a
      brisk increase in Isc (80 microA/cm2). Isc was reduced 2-fold, however, when
      toxins were applied to basolateral membranes. Pretreatment of wild type toxins
      with trypsin in vitro restored the "basolateral" secretory responses to "apical"
      levels. Toxin entry into T84 cells via apical but not basolateral membranes led
      to nicking of the A subunit by a serine-type protease. T84 cells, however, did
      not nick CTR192H, and the secretory response elicited by CTR192H remained
      attenuated even when applied to apical membranes. Thus, T84 cells express a
      serine-type protease(s) fully sufficient for activating the A subunits of CT and
      LT. The protease, however, is only accessible for activation when the toxin
      enters the cell via the apical membrane.

PMID- 9182594
TI  - Phosphatidic acid-mediated phosphorylation of the NADPH oxidase component p47
      phox. Evidence that phosphatidic acid may activate a novel protein kinase.
AB  - Phosphatidic acid (PA), generated by phospholipase D activation, has been linked
      to the activation of the neutrophil respiratory burst enzyme, NADPH oxidase;
      however, the intracellular enzyme targets for PA remain unclear. We have recently
      shown (McPhail, L. C., Qualliotine-Mann, D., and Waite, K. A. (1995) Proc. Natl.
      Acad. Sci. U. S. A. 92, 7931-7935) that a PA-activated protein kinase is involved
      in the activation of NADPH oxidase in a cell-free system. This protein kinase
      phosphorylates numerous endogenous proteins, including p47-phox, a component of
      the NADPH oxidase complex. Phospholipids other than PA were less effective at
      inducing endogenous protein phosphorylation. Several of these endogenous
      substrates were also phosphorylated during stimulation of intact cells by
      opsonized zymosan, an agonist that induces phospholipase D activation. We sought
      to identify the PA-activated protein kinase that phosphorylates p47-phox. The PA
      dependent protein kinase was shown to be cytosolic. cis-Unsaturated fatty acids
      were poor inducers of protein kinase activity, suggesting that the PA-activated
      protein kinase is not a fatty acid-regulated protein kinase (e.g. protein kinase
      N). Chromatographic techniques separated the PA-activated protein kinase from a
      number of other protein kinases known to be activated by PA or to phosphorylate
      p47-phox. These included isoforms of protein kinase C, p21 (Cdc42/Rac)-activated
      protein kinase, and mitogen-activated protein kinase. Gel filtration
      chromatography indicated that the protein kinase has an apparent molecular size
      of 125 kDa. Screening of cytosolic fractions from several cell types and rat
      brain suggested the enzyme has widespread cell and tissue distribution. The
      partially purified protein kinase was sensitive to the same protein kinase
      inhibitors that diminished NADPH oxidase activation and was independent of
      guanosine 5'-3-O-(thio)triphosphate and Ca2+. Phosphoamino acid analysis showed
      that serine and tyrosine residues were phosphorylated on p47-phox by this
      kinase(s). These data indicate that one or more potentially novel protein kinases
      are targets for PA in neutrophils and other cell types. Furthermore, a PA
      activated protein kinase is likely to be an important regulator of the neutrophil
      respiratory burst by phosphorylation of the NADPH oxidase component p47-phox.

PMID- 9182595
TI  - Localisation of neurokinin 3 (NK3) receptor immunoreactivity in the rat
      gastrointestinal tract.
AB  - The localisation of the neurokinin 3 receptor (NK3r) in the rat gastrointestinal
      tract has been studied by using a polyclonal antiserum against the C-terminal
      portion (amino acids 388-452) of the rat NK3r. In the oesophagus,
      immunoreactivity for the NK3r was found on smooth muscle cells of the muscularis
      mucosae. NK3r immunoreactivity was not present on muscle cells of other regions.
      Nerve cell bodies immunoreactive for NK3r were seen in the myenteric and
      submucous plexuses of the small and large intestine, but not in the stomach or
      oesophagus. Immunoreactivity was largely confined to nerve cell surfaces. The
      reaction product was on the cell soma and initial parts of axons. Reactivity was
      not seen on nerve terminals. Immunoreactive nerve cells had Dogiel Type II
      morphology. Patterns of co-localisation of NK3r and immunoreactivity for other
      markers were examined in the ileum, to provide a basis from which to deduce the
      functional identity of NK3r-immunoreactive nerve cells. Most of the NK3r
      immunoreactive nerve cells were also immunoreactive for the calcium-binding
      proteins, calretinin and calbindin, and all were immunoreactive for the NK1
      receptor (NK1r). Nerve cells that were immunoreactive for nitric oxide synthase
      were not immunoreactive for either NK3r or NK1r. The projections of the calbindin
      and calretinin neurons were determined by nerve lesion studies. Their morphology,
      projections to the mucosa and other ganglia and immunoreactivity for the calcium
      binding proteins suggest that the NK3r-immunoreactive neurons are intrinsic
      sensory neurons.

PMID- 9182596
TI  - A morphological anomaly of the dorsal lateral geniculate nucleus in Macaca
      fascicularis.
AB  - In the present report we describe a morphological anomaly of the thalamus. In
      three macaque monkeys (Macaca fascicularis), we observed up to five finger-like
      protrusions that emanated from the posterior pole of the dorsal lateral
      geniculate nucleus (LGN) and extended posteriorly between the lateral pulvinar
      and reticular nucleus of the thalamus. These anomalous fingers measured up to 1.7
      mm in length and contained dense accumulations of neurons and glia. The fingers
      received a direct retinal input from the contralateral eye indicating that they
      were part of the LGN rather than of other adjacent thalamic nuclei. In order to
      determine with which subcompartment(s) of the LGN the fingers were associated
      (parvocellular, magnocellular, or intercalated layers), we examined the
      immunochemical properties and size of neurons in the fingers and LGN
      subcompartments. We concluded that the fingers were not associated with the
      intercalated layers, since neurons in the fingers did not stain with an antibody
      to calbindin-D28k, whereas intercalated neurons stained intensely with this
      antibody. In addition, neurons located in the fingers were significantly smaller
      than those found in the magnocellular layers but were not significantly different
      in size from neurons in the parvocellular layers. We therefore consider that the
      fingers are an anomaly of the parvocellular subcompartment of the LGN.
      Interestingly, in two of the three cases with anomalous fingers, we also observed
      subsidiary parvocellular laminae, suggesting that these two anomalies were
      related. In five additional animals, however, we observed subsidiary
      parvocellular laminae without anomalous fingers. Thus, if there are common
      mechanisms underlying the development of both anomalous fingers and subsidiary
      layers, our data indicate that they do not always result in the concomitant
      expression of both anomalies.

PMID- 9182597
TI  - Developmental expression of the CD15 epitope in the hippocampus of the mouse.
AB  - The developmental expression of the 3-fucosyl-N-acetyl-lactosamine (CD15, Lex,
      SSEA-1) epitope has been examined immunohistochemically in paraffin sections of
      the mouse hippocampus. Labelling appeared initially at E10, with immunostaining
      of the ventricular surface of the hippocampal primordium and in the early
      hippocampal marginal zone. At E12 and E13, a group of cells in the marginal zone
      of the hippocampus was labelled. From E14 to E15, CD15 immunoreactivity
      delineated several boundaries in the developing hippocampal formation. A band of
      labelling was seen at these ages separating the fimbrioglial proliferative
      compartment from the primary dentate neuroepithelium. During late fetal and early
      postnatal life (E19-P5. 5), two strong bands of labelling were visible in the
      stratum lacunosum moleculare and stratum oriens of CA3, and in the marginal zone
      and deeper layers of the subiculum. The bands in CA3 corresponded in position to
      the earliest afferents to the hippocampus from the entorhinal cortex. In later
      postnatal life (from P5.5), astrocytic CD15 labelling predominated in a mosaic
      camouflage pattern, as seen in the adult.

PMID- 9182598
TI  - Apoptosis induced by methylazoxymethanol in developing rat cerebellum:
      organization of the cell nucleus and its relationship to DNA and rRNA
      degradation.
AB  - We present a cytological and biochemical study of the cell death of granule cell
      precursors in developing rat cerebellum following treatment with the cytotoxic
      agent methylazoxymethanol (MAM) during the first postnatal week. The density of
      apoptotic figures per square millimeter progressively increases after 6, 12, 24
      and 44 h of treatment, whereas cells immunoreactive for proliferating cell
      nuclear antigen tend to disappear in the external granular layer (EGL). DNA
      migration on gel electrophoresis reveals a typical ladder pattern of
      internucleosomal cleavage following MAM treatment, whereas gel electrophoresis of
      rRNA shows a conspicuous degradation of both 28S and 18S rRNAs. Ultrastructural
      analysis has revealed the alterations of structures containing chromatin and
      ribonucleoprotein (RNP) in dying cells of the EGL. The typical granular beaded
      configuration of the condensed chromatin changes to a denser, more homogeneous
      texture suggesting nucleosomal disruption. The reorganization of RNP nuclear
      domains is reflected by the appearance of dispersed nucleoplasmic RNP particles
      and the formation of a coiled-body-like structure. However, typical nuclear
      domains involved in the splicing of RNAs, namely interchromatin granule clusters
      and typical "coiled bodies", are not found in apoptotic cells. Intranuclear
      bundles of filaments have also been detected. In the cytoplasm, the presence of
      dispersed single ribosomes is an initial sign of apoptosis. The massive
      dispersion and disruption of ribosomes detected after 24 h and 44 h of MAM
      treatment is reflected by the degradation of both 28S and 18s rRNAs. These
      results show that MAM treatment provides a useful experimental model for the
      study of apoptosis in the developing central nervous system. The organization of
      the cell nucleus in cells undergoing apoptosis clearly reflects a disruption of
      the nuclear compartments involved in transcription and the processing and
      transport of RNA and is related to the patterns of DNA and rRNA degradation.

PMID- 9182599
TI  - Neuropeptide Y, somatostatin, and cholecystokinin of the anterior piriform
      cortex.
AB  - In addition to its role in olfaction and as a primary epileptogenic site, the
      anterior piriform cortex has been suggested to play a role in neuroperception of
      deficiencies or imbalances in physiologically essential amino acids. In recent
      studies, amino acid deficient diets were shown to induce expression of c-fos in
      the anterior piriform cortex within the rapid time frame associated with the
      normal anorectic response to such diets. It became important to examine the
      neurocytochemical architecture of this region for clues as to how and more
      precisely where dietary amino acid deficiency or imbalance might be monitored.
      The relationships of neuropeptide Y-, somatostatin-, and cholecystokinin
      containing neurons were of particular interest because ongoing studies indicate
      that those peptides administered to the anterior piriform cortex alter intake of
      diets deficient in essential amino acids. The neuropeptides were endogenous to
      intrinsic neurons only; none resembled pyramidal projection neurons. Peptidergic
      neurons and fibers were concentrated most heavily in layer III of the
      paleocortex. The cytoarchitecture suggests that neuropeptide Y-, somatostatin-,
      and cholecystokin-containing neurons of the anterior piriform cortex may relate
      synaptically or multisynaptically to local circuit neurons during electrical
      activity, modulation of olfactory information, and neuroperception of essential
      amino acids.

PMID- 9182601
TI  - Prolactin-like immunoreactivity in the granules of neural complex cells in the
      ascidian Halocynthia roretzi.
AB  - Electron-microscopic studies of the neural complex (neural gland, dorsal strand,
      and cerebral ganglion) of an ascidian, Halocynthia roretzi, were performed,
      paying particular attention to the secretory systems. We found that cells
      scattered along the dorsal strand and neural cells in the cerebral ganglion
      contained electron-dense secretory granules of variable size. Immunoelectron
      microscopic studies with an antiserum to bullfrog prolactin revealed that the
      secretory granules (100-250 nm in diameter) of some granulated cells contained a
      prolactin-like substance. Cells belonging to the neural gland and dorsal strand
      neither contained electron-dense granules nor showed immunoreactivity. The
      possibility that cells in the cerebral ganglion and those along the dorsal strand
      are phylogenetic progenitors of vertebrate adenohypophyseal cells is discussed.

PMID- 9182600
TI  - Distribution of ionocytes in the saccular epithelium of the inner ear of two
      teleosts (Oncorhynchus mykiss and Scophthalmus maximus).
AB  - The saccular membranes of trout (Oncorhynchus mykiss) and turbot (Scophthalmus
      maximus) were examined to characterize specialized epithelial cells that might be
      responsible for ion exchange. The approach for localizing cell types was new for
      this tissue, as observations were made with a stereomicroscope and a light
      microscope in order to have a general view of the epithelium. No important
      differences between the two species were seen. The saccular tissue is a monolayer
      epithelium (except for the macula neural zone) surrounded by a layer of
      connective tissue invaded by many blood vessels. The use of the fluorescent probe
      DAPSMI and zinc iodide/osmium fixation-coloration defined two areas in which
      ionocytes were present. In the first, large ionocytes were grouped into a nearly
      complete, crowned meshwork around, but separated from, the macula. In the second
      area, opposite the macula, the ionocytes were smaller, cubical, and grouped in
      patches. Cells rich in Na+, K+-ATPase and carbonic anhydrase II were present in
      both areas. Contrary to previous studies in mammals and fish, ionocytes were also
      found in the epithelium of the saccule.

PMID- 9182602
TI  - Identification, tissue localisation and physiological effect in vitro of a
      neuroendocrine peptide identical to a dipteran Leu-callatostatin in the codling
      moth Cydia pomonella (Tortricidae: Lepidoptera).
AB  - A neuroendocrine peptide of the Leu-callatostatin family, LPVYNFGL-NH2, has been
      isolated from tissue extracts of 5th instar larvae of the codling moth, Cydia
      pomonella (Lepidoptera). It is identical to a peptide previously isolated from
      the blowfly, Calliphora vomitoria (Diptera). The distribution of this peptide
      within the tissues of C. pomonella has been mapped by immunocytochemistry using
      antisera raised against LPVYNFGL-NH2. Midgut endocrine cells contain Leu
      callatostatin immunoreactivity, as do several paired Leu-callatostatin neurones
      in the brain and ventral nerve cord. Within the visceral nervous system, the
      frontal ganglion contains four Leu-callatostatin neurones. Axons from these cells
      combine with others originating from neurones in the brain and project within the
      nervi cardiostomatogastrici to innervate the tissues of the foregut. In
      particular, the oesophageal valve has a prominent ring of Leu-callatostatin
      immunoreactive fibres. The synthetic peptide, LPVYNFGL-NH2, has a potent
      reversible inhibitory effect in vitro on all visible forms of spontaneous
      contractile activity of the foregut, including closure of the oesophageal valve.
      Complete myoinhibition is observed at peptide concentrations from 10(-10 )to 10(
      16) M. These results, in conjunction with the results of similar studies on
      cockroaches, crickets and flies, suggest that the Leu-callatostatins are a
      ubiquitous family of insect neuroendocrine peptides with an important role in the
      control of gut motility.

PMID- 9182603
TI  - Horseradish peroxidase: a reliable or a misleading tool for the investigations on
      the origin of the proteins of the aqueous humor?
AB  - The concept of the blood-aqueous barrier is largely based on the use of
      horseradish peroxidase (HRP). The present investigation was designed to check its
      reliability as a macromolecular tracer, especially with regard to the transport
      of plasma proteins. Rabbits were killed 5 min to 24 h after being intravenously
      injected with HRP. The tracer diffused rapidly, reaching the aqueous humor of the
      eye in 3 min or less and was detected at high concentration in the narrow space
      between the outer epithelial layer of the ciliary epithelium and the wall of the
      pervious capillaries in the stroma of the processes. HRP appeared to migrate from
      the blood to the posterior chamber, permeating the tight junctions, viz., the
      anatomical basis of the blood-aqueous barrier. It was detected at higher
      concentration at the anterior surface of the iris, at short time intervals; this
      was interpreted as penetration of the tracer from the aqueous humor of the
      anterior chamber. The choroid was also labeled in continuation with the reaction
      in the stroma of the pars plana of the ciliary body which, in turn, sometimes
      reached the iris root. Therefore, the pervious blood vessels of the choroid could
      be a source of macromolecules for the iris root. HRP also induced the formation
      of lysosomes in the ciliary epithelium. This can hardly be accepted as the way in
      which plasma proteins are physiologically transported to the aqueous humor.
      However, the pathway of HRP migration over short time intervals seems to be in
      agreement with previous research indicating that the entrance of serum albumin
      into the posterior chamber is the first step of its incorporation into the
      aqueous humor.

PMID- 9182604
TI  - Ductin, a component of the V-ATPase, is developmentally regulated in Heliothis
      virescens midgut, and anti-ductin antibodies label lateral membranes.
AB  - We previously cloned from Heliothis virescens a 16-kDa protein that is homologous
      to other ductin sequences. We also reported its immunolocalization with a
      specific affinity-purified anti-peptide antibody in the midgut and Malpighian
      tubule of feeding larvae, and concluded that the cloned proteolipid encodes the V
      ATPase proton-transporting subunit c from the V0 sector. We now present the
      immunolocalization of this protein in the midgut during the L4-L5 larval molt and
      early post-ecdysis into the fifth instar in H. virescens. The results show that
      the spatial expression of the 16-kDa protein is developmentally regulated.
      Labeling by anti-peptide antibody varies during the molt in the midgut goblet
      cell apical plasma membrane and the goblet cell apical valve. Epifluorescence and
      confocal microscopy revealed strong anti-ductin labeling in areas of cell-to-cell
      contact during the molt, and during early post-ecdysis into the fifth larval
      instar. The characteristic labeling pattern observed in areas of cell-to-cell
      contact is consistent with the claimed involvement of ductins in gap junctions.
      Conclusive evidence for the presence of the 16-kDa protein in areas of cell-to
      cell contact in the midgut of feeding larvae is, however, lacking. V-ATPase
      regulation during the molt was also investigated by simultaneous
      immunohistochemistry with an anti-B subunit antiserum, a probe for the V1 sector.

PMID- 9182606
TI  - Type II collagen and TGF-betas in developing and aging porcine mandibular
      condylar cartilage: immunohistochemical studies.
AB  - Transforming growth factor-betas (TGF-betas) have been associated with the
      development and maintenance of articular cartilage. However, no studies have
      addressed their role in the postnatal development of mandibular condylar
      cartilage. This investigation represents the first immunohistochemical
      characterization of TGF-beta isoforms and type II collagen in porcine mandibular
      condylar cartilage from various age groups. Furthermore, it is the first
      description of possible age-related changes in the expression of these proteins
      during postnatal development of this tissue. Condylar cartilage was dissected
      from freshly harvested temporomandibular joints of newborn, 6-, 12-, 24-, and 36
      month-old farm swine. TGF-beta1, TGF-beta2, TGF-beta3, and type II collagen were
      localized via standard immunohistochemical procedures. An immunoblot technique
      was employed to compare the relative amount of each protein present in the
      various age groups. Immunoreactivity was detected in mandibular condylar
      cartilage for all three isoforms of TGF-beta and for Type II collagen. All age
      groups demonstrated some evidence of immunostaining, primarily in the cytoplasm
      of cells from most zones of the cartilage. Immunoblot results indicated that TGF
      beta isoforms had individualized patterns of expression. When newborn protein
      levels were taken as the baseline, TGF-beta1 demonstrated a significant increase
      at ages 24 and 36 months. TGF-beta2 significantly increased at 6, 12, 24, and 36
      months (peak levels at 24 months; similar levels at 6, 12, and 36 months),
      whereas TGF-beta3 remained stable at all ages. Type II collagen demonstrated
      increases that paralleled the increased levels of TGF-beta1 and TGF-beta2 at 24
      and 36 months.

PMID- 9182605
TI  - Differentiation-induced changes in the content, secretion, and subcellular
      distribution of lysosomal cathepsins in the human colon cancer HT-29 cell line.
AB  - Enterocyte-like differentiated HT-29 colon carcinoma cells were shown to contain
      far higher intracellular levels of activity of lysosomal cathepsins B, D, and L
      than their undifferentiated counterparts. In the latter, inhibition of lysosomal
      functions by leupeptin or ammonium chloride led to a marked increase in the cell
      associated activity of the three cathepsins. High levels of pro-cathepsins B, D,
      and L were found in the culture media of both HT-29 cell populations. Ammonium
      chloride and chloroquine, which are known to impair the mannose-6-phosphate
      dependent trafficking of lysosomal-targeted proteins, did not increase the
      secretion of the three cathepsins in either undifferentiated or differentiated
      cultures of HT-29 cells. Analyses by cell fractionation revealed heterogeneities
      with regard to the density and the content of lysosomal cathepsins between the
      two cell populations. Leupeptin induced the accumulation of mature lysosomal
      cathepsins B and L in light density organelles in undifferentiated HT-29 cells.
      Altogether, these data demonstrate that (1) the expression and subcellular
      distribution of cathepsins B, D, and L in HT-29 cells are influenced by their
      state of enterocytic differentiation, (2) the segregation of lysosomal cathepsins
      is largely inefficient in this tumor cell line and does not increase upon
      differentiation, and (3) the mannose-6-phosphate-receptor-dependent pathway plays
      a minor role in the sorting of the three cathepsins, both in undifferentiated and
      enterocytic-differentiated HT-29 cells.

PMID- 9182607
TI  - Disturbances of the secretory stage of amelogenesis in fluorosed deer teeth: a
      scanning electron-microscopic study.
AB  - Structural changes resulting from fluoride-induced disturbances of the secretory
      stage of amelogenesis were studied in fluorosed dental enamel of ten permanent
      premolars and molars from roe deer (Capreolus capreolus) and red deer (Cervus
      elaphus). The fluorosed enamel exhibited surface hypoplasias of different depths
      and extents and an associated loss of its normal prism/interprism structure. The
      occurrence of such aprismatic enamel either was restricted to grossly accentuated
      and hypomineralized incremental (calciotraumatic) bands or affected more extended
      areas to the bottom of the hypoplastic lesions. The fluoride-induced disturbance
      of the secretory functions of the cells had thus been either temporary or
      permanent. Layers of aprismatic enamel were regarded as denoting periods of
      reduced enamel matrix formation by secretory ameloblasts lacking the distal,
      i.e., the prism-forming, portions of their Tomes processes. Our observations also
      indicated that the transition from the presecretory to the secretory stage of
      amelogenesis could be affected by fluoride, thereby preventing the ameloblasts
      from achieving their normal secretory function and from establishing fully formed
      Tomes processes. Aprismatic enamel was formed throughout the secretory stage of
      amelogenesis at these locations. The most severe ameloblast reaction that could
      be deduced from our findings was an abrupt cessation of enamel matrix secretion.
      Some of the pathological changes observed in fluorosed deer enamel showed
      striking similarities to those reported in rodents after acute parenteral
      fluoride dosing. Thus, periods of especially elevated plasma-fluoride levels in
      chronically fluoride-stressed deer can cause a disruption in the function of
      secretory ameloblasts similar to that following acute fluoride dosing in rodents.

PMID- 9182608
TI  - Ultrastructural identification of the c-kit-expressing interstitial cells in the
      rat stomach: a comparison of control and Ws/Ws mutant rats.
AB  - Interstitial cells in the circular muscle layer of the stomach of the Ws/Ws
      mutant rat, which lacks c-kit-expressing cells, and its siblings have been
      studied by electron microscopy. In the sibling control rats, two types of
      interstitial cells are found lying in close association with nerve bundles. Cells
      of the first type are characterized by electron-dense cytoplasm containing
      abundant mitochondria, granular endoplasmic reticulum, and Golgi apparatus.
      Intermediate filaments are richly distributed throughout the perinuclear region
      and the cell processes. Caveolae, subsurface cisterns, and indistinct basal
      lamina are observed along the cell membrane. The most conspicuous feature of this
      cell type is the existence of many large gap junctions that interconnect with the
      same type of cell, smooth muscle cells, or cells of the second type. Cells of the
      second type show an ultrastructure similar to fibroblasts, viz., a well-developed
      Golgi apparatus and granular endoplasmic reticulum whose cisterns often show a
      dilated form and contain flocculent material. Unlike typical fibroblasts,
      however, cells of this type also form many gap junctions with cells of the first
      type and smooth muscle cells. Both types of cells are observed in close
      apposition to nerve varicosities. Since cells of the first type are absent in the
      Ws/Ws mutant rat, we concluded that they correspond to c-kit-expressing cells and
      to interstitial cells of Cajal.

PMID- 9182609
TI  - Light-microscopical investigation of the distribution of extracellular matrix
      molecules and calcifications in human dental pulps of various ages.
AB  - The distribution of extracellular matrix molecules, especially collagen types I,
      III, V, and VI, in the extracellular matrix of the connective tissue of human
      dental pulp of various ages was studied by polarization and indirect
      immunofluorescence microscopy by using a conventional fluorescence microscope and
      a confocal laser scanning microscope. Polarization and immunofluorescence
      microscopy of paraffin sections showed thick fibers of collagen type I, which
      represented the main component of the connective tissue matrix of the dental
      pulp. By indirect immunofluorescence, thin fibers and small bundles of collagen
      type III were determined to be one of the main fibrillar elements present in the
      dental pulp matrix. Collagen type IV was detected by a clear intense staining of
      the basement membrane of blood vessels at all ages examined. Collagens type V and
      VI formed a dense meshwork of thin microfibrils throughout the stroma of the
      connective tissue of the dental pulp. These fibers were localized around blood
      vessels and appeared to be enriched in the subodontoblastic layer. Investigations
      by means of confocal laser scanning microscopy revealed fibers of collagen type
      VI spiralling between fully differentiated odontoblasts toward the predentin
      layer. With advancing age, the connective tissue matrix appeared to be condensed
      and aggregates of thick fiber bundles could be observed. Furthermore, the
      participation of various collagen types in the composition of pulp stones was
      shown. These calcifications and diffuse calcifications increased in frequency
      with advancing age in a statistically significant manner.

PMID- 9182610
TI  - Thrombin regulates nerve growth factor secretion from vascular, but not bladder
      smooth muscle cells.
AB  - The production of nerve growth factor (NGF) in peripheral organs may play a role
      in the pathophysiology of hypertension and in obstructive disorders of the
      bladder outlet. We have been examining the cellular processes of NGF delivery and
      secretion in smooth muscle. NGF secretion from vascular smooth muscle cells
      (VSMCs) cultured from genetically hypertensive (WKHT), hyperactive (WKHA), and a
      control Wistar rat strain were assayed using a two-site ELISA of the culture
      media. Bladder smooth muscle cells (BSMCs) from the Wistar strain were also
      studied. The serine protease, thrombin, increased NGF secretion from all types of
      VSMCs but had no effect on Wistar BSMCs. The thrombin-mediated increase in NGF
      secretion was prevented by actinomycin D and cycloheximide, suggesting that RNA
      transcription and protein synthesis are required. The effect of thrombin was
      additive with a phorbol ester-induced elevation in NGF secretion rates from 4 to
      6 h and was attenuated by a 24-h downregulation of protein kinase C. These
      results suggest that extracellular protease activity may regulate NGF secretion
      in smooth muscle. Thrombin may act in response to vascular injury, increasing NGF
      secretion from VSMCs, initiating VSMC migration, and preparing the VSMCs for
      reinnervation following an insult.

PMID- 9182611
TI  - Immunocytochemical detection and cytomorphology of lymphocyte subpopulations in a
      teleost fish Dicentrarchus labrax.
AB  - The monoclonal antibodies DLT15 and DLIg3 directed against thymocytes and serum
      immunoglobulins of the sea bass (Dicentrarchus labrax, L.) were used to study
      cells from the thymus, head kidney, spleen, gut-associated lymphoid tissue and
      peripheral blood leukocytes of this fish by immunofluorescence and pre-embedding
      immunoelectron microscopy. Immunofluorescence and flow cytometry of leukocyte
      fractions revealed a large number of DLT15-positive cells in the thymus
      (approximately 80%) and intestine (approximately 55%) and fewer cells in the
      spleen (approximately 7%), head kidney (approximately 6%) and peripheral blood
      (approximately 3%). DLT15-positive cells had two main morphologies, both
      detectable among thymocytes: a large round heterochromatic nucleus with light
      sparse cytoplasm (type a) and an irregular and heterocromatic nucleus with
      cytoplasm rich in polysomes and mitochondria (type b). Type b was most
      represented in spleen, head kidney, intestine and blood. We suggest that the type
      b morphology represents more differentiated lymphocytes. Flow cytometry revealed
      numerous DLIg3-positive cells in the head kidney (approximately 33%), spleen
      (approximately 30%) and peripheral blood leukocytes (approximately 21%) and fewer
      positive cells in the intestine (approximately 3%) and thymus (approximately 2%).
      DLIg3-positive cells had the morphology of lymphocytes (with a large round
      nucleus) or macrophages in all tissues. Plasma cells lacked membrane
      immunoreactivity. This is the first ultrastructural characterisation of putative
      T- and B-lymphocyte subpopulations in a fish species; these subpopulations are
      differentially distributed in teleost lymphoid organs.

PMID- 9182613
TI  - Immunohistochemical localization of the small proteoglycans decorin and biglycan
      in human intervertebral discs.
AB  - Immunohistochemistry was used to study the presence and distribution of the core
      proteins of the small proteoglycans decorin and biglycan in the various
      compartments of human intervertebral discs. Both proteoglycans could be found in
      the outer tendon-like parts of the annulus fibrosus, indicating their potential
      role in collagen network formation and biomechanical stress resistance. The loss
      of both proteoglycans in the annulus of individuals older than 50 years reflects
      a normal age-related change. In the nucleus pulposus, decorin could be found in
      fibrillar areas of the interterritorial matrix, thereby indicating co
      localization of decorin with fibrils containing type II collagen. Biglycan was
      present in the extracellular matrix of the nucleus pulposus of adults. The
      pericellular immunoreactive rims observed around nucleus pulposus cells and giant
      chondrones indicated local biosynthetic activity for these small proteoglycans.
      The staining patterns in cartilage endplates resembled those found in human
      hyaline articular cartilage.

PMID- 9182612
TI  - Differential distribution of five members of the matrix metalloproteinase family
      and one inhibitor (TIMP-1) in human liver and skin.
AB  - Matrix metalloproteinases represent a family of zinc-dependent proteolytic
      enzymes thought to be involved in normal and disease-related tissue remodeling
      processes. Increasing information about these enzymes is becoming available
      concerning their primary sequences, regulation at the mRNA level, activation of
      proenzymes, and modulation of enzyme activity by tissue inhibitors. In contrast,
      their morphological distribution and biological functions in normal tissues are
      poorly understood. In the present report, the comparative distribution of five
      members (gelatinase-A, gelatinase-B, matrilysin, stromelysin-1, and stromelysin
      3) of the matrix metalloproteinase family and of one inhibitor (TIMP-1) has been
      morphologically analyzed in human liver and skin with the aid of new monospecific
      antibodies. Because of their common designation as matrix proteinases, these
      enzymes might have been expected to be distributed throughout these tissues, or
      at least in the connective tissue. However, each member of the family produces a
      highly specific pattern, staining structures such as arteriolar smooth muscle
      cells, myoepithelial cells in secretory portions or the luminal lining in
      excretory ducts of dermal sweat glands, liver bile canaliculi, or structures
      surrounding peripheral nerve axons. No reactivity is detected in rat tissues.

PMID- 9182614
TI  - Spontaneous formation of intercellular bile canaliculi and hybrid biliary
      pancreatic canaliculi in co-culture of hepatocytes and exocrine pancreas cells
      from carp.
AB  - When cultured together in a primary serum-free hormone-free system, hepatocytes
      and exocrine pancreas cells from the carp, Cyprinus carpio, spontaneously
      establish unique morphological structures that do not occur in vivo. These
      structures include intercellular bile canaliculi between neighbouring hepatocytes
      and hybrid canaliculi between hepatocytes and pancreas cells. In vivo, carp
      hepatocytes form only unicellular bile canaliculi; hybrid canaliculi between
      hepatocytes and exocrine pancreas cells do not exist at all in nature. This study
      shows that, in an artificial environment, cells are able spontaneously to
      establish novel morphological structures that are absent in the animal from which
      the cells have been obtained.

PMID- 9182650
TI  - Arteriosclerosis.
AB  - The history and todays knowledge on the pathogenesis of arteriosclerosis
      emphasizing the importance of cholesterol concentration in plasma for the
      development of atherosclerosis is summarized. For proving the lipid hypothesis
      careful patient observation and new findings of molecular biology have added
      important information. More and more details on the complex interaction between
      risk factors, endothelial cells, smooth muscle cells, growth factors and the
      coagulation system are clarified. The increasing knowledge on the
      arteriosclerotic process has led to the fascinating situation, that for the first
      time in arteriosclerosis research causal approaches for therapy are under
      investigation.

PMID- 9182651
TI  - New and classical risk factors--the Munster heart study (PROCAM).
AB  - A total of 4,849 male participants of the prospective cardiovascular Munster
      Study (PROCAM), aged 40 - 65 years underwent extensive screening for
      cardiovascular risk factors before 1986 and were subsequently followed up for at
      least 8 years. During this time 189 non-fatal and 49 fatal myocardial infarctions
      occurred, 28 men suffered a sudden cardiac death and 169 persons died of other
      causes. Using multivariate statistical methods we confirmed that age, increased
      LDL cholesterol levels, decreased HDL cholesterol levels, high blood pressure,
      cigarette smoking, diabetes mellitus, angina pectoris and a positive family
      history are important risk factors for a myocardial infarction or cardiac death.
      The results of the PROCAM Study demonstrate that elevated triglycerides are an
      independent risk factor for an early myocardial infarction or cardiac death.
      Using a multiple logistic function analysis an algorithm for the assessment of
      the global risk was derived from the data. The observed incidence of coronary
      heart disease rises sharply as the global risk increases, thus permitting the use
      of this algorithm in clinical practice for the assessment of the individual risk
      of myocardial infarction. Risk factors such as lipoprotein(a) and coagulation
      factors may improve the predictive value of this algorithm. Furthermore it is
      expected that the exploration of genetic defects will strongly increase the
      predictive value and precise determination of individual risk.

PMID- 9182652
TI  - Nutrition and cardiovascular disease.
AB  - The association between nutrition and coronary heart disease is mainly due to the
      effect of nutrients on serum lipids and lipoproteins. Cholesterol intake does not
      play a very important role for plasma cholesterol although there is a strong
      interindividual difference in response. The intake of saturated fatty acids
      strongly negatively affects plasma low-density lipoprotein cholesterol
      concentration while mono- and polyunsaturated fatty acids are generally regarded
      as beneficial. Omega-3 fatty acids mainly decrease triglyceride concentration
      while omega-6 polyunsaturated fatty acids mainly affect low-density lipoprotein
      cholesterol. Other nutrients which affect risk for coronary heart disease are
      dietary fiber, calcium, magnesium, iron, antioxidants as well as vitamins.
      Dietary fiber decrease intake of calories and fat, while iron and antioxidants
      play a role in oxidative modification of low-density lipoproteins. A low intake
      would lead to an accelerated uptake of low-density lipoprotein into the
      macrophage. Yet, intervention studies have not shown conclusively the benefit of
      a high-dose supplementation of the antioxidants vitamin E or beta-carotene on
      coronary heart disease. Homocysteine plasma concentration is influenced by folate
      as well as vitamin B6 and B12. Whether a high-dose supplementation with these
      substances does not only decrease plasma concentrations of homocysteine but also
      positively influence the course of coronary heart disease remains to be
      established.

PMID- 9182653
TI  - Physical activity and lipoprotein metabolism: epidemiological evidence and
      clinical trials.
AB  - Prospective epidemiological studies have proven a close link between the
      lipoprotein profile and cardiovascular morbidity and mortality. As physical
      activity is accepted as a significant factor improving physical fitness and
      lipoprotein metabolism, there is evidence that physically active men have a lower
      cardiovascular risk due to their higher metabolic fitness. Physical activity and
      physical fitness are generally linked to higher HDL cholesterol and lower LDL
      cholesterol as well as lower triglyceride and insulin levels. However, in cross
      sectional studies the differences in lipoprotein cholesterol evaluated by routine
      measures in healthy physically active individuals and sedentary controls are only
      minor compared to therapeutical aims. The impact of exercise and training is
      often more significant when the effect of exercise on lipoprotein subfractions
      and apolipoprotein levels are taken into account. Dramatic differences can be
      documented in concentrations of cardioprotective HDL subset2 and atherogenic
      small, dense LDL subset6 levels in relation to the individual status of aerobic
      fitness and body composition in adults. These observations indicate that the
      preventive and therapeutical use of physical activity is of particular
      significance in a population of cardiovascular risk or patients with reduced
      daily activity. Our own experience in clinical trials shows that even in short
      term programs (4 weeks to 6 months) changes in activity and eating behavior may
      lead to important improvements of the metabolic risk and lipid profile.
      Understanding the complex interaction between exercise and metabolic control of
      the lipid profile as well as the correlation with other risk parameters will
      improve the knowledge of prescribing exercise programs in patients at risk.

PMID- 9182654
TI  - Drug therapy of severe hypercholesterolemia.
AB  - Lowering of plasma cholesterol and particularly of LDL cholesterol has been shown
      to be an effective way of primary and secondary prophylaxis of coronary heart
      disease. A broad range of drugs is available (bile acid binding resins, HMG CoA
      reductase inhibitors, fibrates, nicotinic acid, probucol, beta-sitosterol) for
      therapy. The choice of the drug is based on the efficacy, possible side effects
      and proven effects on coronary heart disease.

PMID- 9182655
TI  - Long term effect of LDL apheresis on coronary heart disease.
AB  - LDL-apheresis is a treatment option for patients with coronary heart disease and
      severe hypercholesterolemia not adequately responding to drug treatment. 34
      patients (21 men, 13 women), aged 47 +/- 9 years, with coronary heart disease and
      heterozygous familial hypercholesterolemia not adequately responsive to lipid
      lowering drugs received weekly (4 patients biweekly) LDL apheresis for 3.5 +/-
      2.5 years, after 0.5 - 3.0 years simvastatin in the maximally tolerable dose was
      added. Baseline LDL cholesterol concentration under diet and lipid lowering drugs
      in the patients receiving immunoadsorption, dextran sulfate adsorption and HELP
      apheresis was 265.4 +/- 54.9, 230.8 +/- 75.8 and 253.7 +/- 55.7 mg/dl,
      respectively. The calculated mean LDL cholesterol concentration of the last 5
      treatments of the observation period was 123.7 +/- 22.8, 126.8 +/- 26.7 and 138.8
      +/- 19.7 mg/dl, respectively. The evaluation of coronary angiographies revealed a
      definite regression of coronary lesions in 3 patients (8.8%), in all other
      patients there was a stop in progression. 3 patients died of cardiac
      complications during the observation period. We conclude that aggressive lipid
      lowering with combined LDL-apheresis and drugs can stabilize coronary
      atherosclerosis in most patients with refractory hypercholesterolemia.

PMID- 9182656
TI  - Integral membrane proteins of the nuclear envelope are dispersed throughout the
      endoplasmic reticulum during mitosis.
AB  - We have analyzed the fate of several integral membrane proteins of the nuclear
      envelope during mitosis in cultured mammalian cells to determine whether nuclear
      membrane proteins are present in a vesicle population distinct from bulk ER
      membranes after mitotic nuclear envelope disassembly or are dispersed throughout
      the ER. Using immunofluorescence staining and confocal microscopy, we compared
      the localization of two inner nuclear membrane proteins (laminaassociated
      polypeptides 1 and 2 [LAP1 and LAP2]) and a nuclear pore membrane protein (gp210)
      to the distribution of bulk ER membranes, which was determined with lipid dyes
      (DiOC6 and R6) and polyclonal antibodies. We found that at the resolution of this
      technique, the three nuclear envelope markers become completely dispersed
      throughout ER membranes during mitosis. In agreement with these results, we
      detected LAP1 in most membranes containing ER markers by immunogold electron
      microscopy of metaphase cells. Together, these findings indicate that nuclear
      membranes lose their identity as a subcompartment of the ER during mitosis. We
      found that nuclear lamins begin to reassemble around chromosomes at the end of
      mitosis at the same time as LAP1 and LAP2 and propose that reassembly of the
      nuclear envelope at the end of mitosis involves sorting of integral membrane
      proteins to chromosome surfaces by binding interactions with lamins and
      chromatin.

PMID- 9182658
TI  - A transfected sialyltransferase that is elevated in breast cancer and localizes
      to the medial/trans-Golgi apparatus inhibits the development of core-2-based O
      glycans.
AB  - The alpha2,3 sialyltransferase, alpha2,3 SAT (O), catalyzes the transfer of
      sialic acid to Galbeta1,3 N-acetyl-D-galactosamine (GalNAc) (core-1) in mucin
      type O-glycosylation, and thus terminates chain extension. A Core-2 branch can
      also be formed from core-1 by the core-2 beta1,6 N-acetyl-d-glucosamine
      transferase (beta1,6 GlcNAc T) that leads to chain extension. Increased levels of
      the alpha2,3 SAT (O) and decreased levels of the core-2 beta1,6 GlcNAc T are seen
      in breast cancer cells and correlate with differences in the structure of the O
      glycans synthesized (Brockhausen et al., 1995; Lloyd et al., 1996). Since in
      mucin type O-glycosylation sugars are added individually and sequentially in the
      Golgi apparatus, the position of the transferases, as well as their activity, can
      determine the final structure of the O-glycans synthesized. A cDNA coding for the
      human alpha2,3 SAT (O) tagged with an immunoreactive epitope from the myc gene
      has been used to map the position of the glycosyltransferase in nontumorigenic
      (MTSV1-7) and malignant (T47D) breast epithelial cell lines. Transfectants were
      analyzed for expression of the enzyme at the level of message and protein, as
      well as for enzymic activity. In T47D cells, which do not express core-2 beta1,6
      GlcNAc T, the increased activity of the sialyltransferase correlated with
      increased sialylation of core-1 O-glycans on the epithelial mucin MUC1.
      Furthermore, in MTSV1-7 cells, which do express core-2 beta1,6 GlcNAc T, an
      increase in sialylated core-1 structures is accompanied by a reduction in the
      ratio of GlcNAc: GalNAc in the O-glycans attached to MUC1, implying a decrease in
      branching. Using quantitative immunoelectron microscopy, the sialyltransferase
      was mapped to the medial- and trans-Golgi cisternae, with some being present in
      the TGN. The data represent the first fine mapping of a sialyltransferase
      specifically active in O-glycosylation and demonstrate that the structure of O
      glycans synthesized by a cell can be manipulated by transfecting with recombinant
      glycosyltransferases.

PMID- 9182657
TI  - Partitioning of the Golgi apparatus during mitosis in living HeLa cells.
AB  - The Golgi apparatus of HeLa cells was fluorescently tagged with a green
      fluorescent protein (GFP), localized by attachment to the NH2-terminal retention
      signal of N-acetylglucosaminyltransferase I (NAGT I). The location was confirmed
      by immunogold and immunofluorescence microscopy using a variety of Golgi markers.
      The behavior of the fluorescent Golgi marker was observed in fixed and living
      mitotic cells using confocal microscopy. By metaphase, cells contained a constant
      number of Golgi fragments dispersed throughout the cytoplasm. Conventional and
      cryoimmunoelectron microscopy showed that the NAGT I-GFP chimera (NAGFP)-positive
      fragments were tubulo-vesicular mitotic Golgi clusters. Mitotic conversion of
      Golgi stacks into mitotic clusters had surprisingly little effect on the polarity
      of Golgi membrane markers at the level of fluorescence microscopy. In living
      cells, there was little self-directed movement of the clusters in the period from
      metaphase to early telophase. In late telophase, the Golgi ribbon began to be
      reformed by a dynamic process of congregation and tubulation of the newly
      inherited Golgi fragments. The accuracy of partitioning the NAGFP-tagged Golgi
      was found to exceed that expected for a stochastic partitioning process. The
      results provide direct evidence for mitotic clusters as the unit of partitioning
      and suggest that precise regulation of the number, position, and compartmentation
      of mitotic membranes is a critical feature for the ordered inheritance of the
      Golgi apparatus.

PMID- 9182659
TI  - Glucose transporter (GLUT-4) is targeted to secretory granules in rat atrial
      cardiomyocytes.
AB  - The insulin-responsive glucose transporter GLUT-4 is found in muscle and fat
      cells in the trans-Golgi reticulum (TGR) and in an intracellular tubulovesicular
      compartment, from where it undergoes insulin-dependent movement to the cell
      surface. To examine the relationship between these GLUT-4-containing compartments
      and the regulated secretory pathway we have localized GLUT-4 in atrial
      cardiomyocytes. This cell type secretes an antihypertensive hormone, referred to
      as the atrial natriuretic factor (ANF), in response to elevated blood pressure.
      We show that GLUT-4 is targeted in the atrial cell to the TGR and a tubulo
      vesicular compartment, which is morphologically and functionally
      indistinguishable from the intracellular GLUT-4 compartment found in other types
      of myocytes and in fat cells, and in addition to the ANF secretory granules.
      Forming ANF granules are present throughout all Golgi cisternae but only become
      GLUT4 positive in the TGR. The inability of cyclohexamide treatment to effect the
      TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory
      granules at the TGR via the recycling pathway and not via the biosynthetic
      pathway. These data suggest that a large proportion of GLUT-4 must recycle via
      the TGR in insulin-sensitive cells. It will be important to determine if this is
      the pathway by which the insulin-regulatable tubulo-vesicular compartment is
      formed.

PMID- 9182660
TI  - Structural requirements for basolateral sorting of the human transferrin receptor
      in the biosynthetic and endocytic pathways of Madin-Darby canine kidney cells.
AB  - In polarized Madin-Darby canine kidney (MDCK) cells, the transferrin receptor
      (TR) is selectively delivered to the basolateral surface, where it internalizes
      transferrin via clathrin-coated pits and recycles back to the basolateral border.
      Mutant tailless receptors are sorted randomly in both the biosynthetic and
      endocytic pathways, indicating that the basolateral sorting of TR is dependent
      upon a signal located within the 61-amino acid cytoplasmic domain. To identify
      the basolateral sorting signal of TR, we have analyzed a series of mutant human
      TR expressed in MDCK cells. We find that residues 19-41 are sufficient for
      basolateral sorting from both the biosynthetic and endocytic pathways and that
      this is the only region of the TR cytoplasmic tail containing basolateral sorting
      information. The basolateral sorting signal is distinct from the YTRF
      internalization signal contained within this region and is not tyrosine based.
      Detailed functional analyses of the mutant TR indicate that residues 29-35 are
      the most important for basolateral sorting from the biosynthetic pathway. The
      structural requirements for basolateral sorting of internalized receptors from
      the endocytic pathway are not identical. The most striking difference is that
      alteration of G31DNS34 to YTRF impairs basolateral sorting of newly synthesized
      receptors from the biosynthetic pathway but not internalized receptors from the
      endocytic pathway. Also, mutations have been identified that selectively impair
      basolateral sorting of internalized TRs from the endocytic pathway without
      affecting basolateral sorting of newly synthesized receptors. These results imply
      that there are subtle differences in the recognition of the TR basolateral
      sorting signal by separate sorting machinery located within the biosynthetic and
      endocytic pathways.

PMID- 9182661
TI  - Enlarged peroxisomes are present in oleic acid-grown Yarrowia lipolytica
      overexpressing the PEX16 gene encoding an intraperoxisomal peripheral membrane
      peroxin.
AB  - Pex mutants of the yeast Yarrowia lipolytica are defective in peroxisome
      assembly. The mutant strain pex16-1 lacks morphologically recognizable
      peroxisomes. Most peroxisomal proteins are mislocalized to a subcellular fraction
      enriched for cytosol in pex16 strains, but a subset of peroxisomal proteins is
      localized at, or near, wild-type levels to a fraction typically enriched for
      peroxisomes. The PEX16 gene was isolated by functional complementation of the
      pex16-1 strain and encodes a protein, Pex16p, of 391 amino acids (44,479 D).
      Pex16p has no known homologues. Pex16p is a peripheral protein located at the
      matrix face of the peroxisomal membrane. Substitution of the carboxylterminal
      tripeptide Ser-Thr-Leu, which is similar to the consensus sequence of peroxisomal
      targeting signal 1, does not affect targeting of Pex16p to peroxisomes. Pex16p is
      synthesized in wild-type cells grown in glucose-containing media, and its levels
      are modestly increased by growth of cells in oleic acid-containing medium.
      Overexpression of the PEX16 gene in oleic acid- grown Y. lipolytica leads to the
      appearance of a small number of enlarged peroxisomes, which contain the normal
      complement of peroxisomal proteins at levels approaching those of wild-type
      peroxisomes.

PMID- 9182662
TI  - A nuclear-coded chloroplastic inner envelope membrane protein uses a soluble
      sorting intermediate upon import into the organelle.
AB  - The chloroplastic inner envelope protein of 110 kD (IEP110) is part of the
      protein import machinery in the pea. Different hybrid proteins were constructed
      to assess the import and sorting pathway of IEP110. The IEP110 precursor
      (pIEP110) uses the general import pathway into chloroplasts, as shown by the
      mutual exchange of presequences with the precursor of the small subunit of
      ribulose-1,5-bisphosphate carboxylase (pSSU). Sorting information to the
      chloroplastic inner envelope is contained in an NH2-proximal part of mature
      IEP110 (110N). The NH2-terminus serves to anchor the protein into the membrane.
      Large COOH-terminal portions of this protein (80-90 kD) are exposed to the
      intermembrane space in situ. Successful sorting and integration of IEP110 and the
      derived constructs into the inner envelope are demonstrated by the
      inaccessability of processed mature protein to the protease thermolysin but
      accessibility to trypsin, i.e., the imported protein is exposed to the
      intermembrane space. A hybrid protein consisting of the transit sequence of SSU,
      the NH2-proximal part of mature IEP110, and mature SSU (tpSSU-110N-mSSU) is
      completely imported into the chloroplast stroma, from which it can be recovered
      as soluble, terminally processed 110NmSSU. The soluble 110N-mSSU then enters a
      reexport pathway, which results not only in the insertion of 110N-mSSU into the
      inner envelope membrane, but also in the extrusion of large portions of the
      protein into the intermembrane space. We conclude that chloroplasts possess a
      protein reexport machinery for IEPs in which soluble stromal components interact
      with a membrane-localized translocation machinery.

PMID- 9182664
TI  - Type II myosin heavy chain encoded by the myo2 gene composes the contractile ring
      during cytokinesis in Schizosaccharomyces pombe.
AB  - We cloned the myo2 gene of Schizosaccharomyces pombe, which encodes a type II
      myosin heavy chain, by virtue of its ability to promote diploidization in fission
      yeast cells. The myo2 gene encodes 1,526 amino acids in a single open reading
      frame. Myo2p shows homology to the head domains and the coiledcoil tail of the
      conventional type II myosin heavy chain and carries putative binding sites for
      ATP and actin. It also carries the IQ motif, which is a presumed binding site for
      the myosin light chain. However, Myo2p apparently carries only one IQ motif,
      while its counterparts in other species have two. There are nine proline
      residues, which should break alpha-helix, in the COOH-terminal coiled-coil region
      of Myo2p. Thus, Myo2p is rather unusual as a type II myosin heavy chain.
      Disruption of myo2 inhibited cell proliferation. myo2Delta cells showed normal
      punctate distribution of interphase actin, but they produced irregular actin
      rings and septa and were impaired in cell separation. Overproduction of Myo2p was
      also lethal, apparently blocking actin relocation. Nuclear division proceeded
      without actin ring formation and cytokinesis in cells overexpressing Myo2p,
      giving rise to multinucleated cells with dumbbell morphology. Analysis using
      tagged Myo2p revealed that Myo2p colocalizes with actin in the contractile ring,
      suggesting that Myo2p is a component of the ring and responsible for its
      contraction. Furthermore, genetic evidence suggested that the acto-myosin system
      may interact with the Ras pathway, which regulates mating and the maintenance of
      cell morphology in S. pombe.

PMID- 9182663
TI  - Unconventional myosins in inner-ear sensory epithelia.
AB  - To understand how cells differentially use the dozens of myosin isozymes present
      in each genome, we examined the distribution of four unconventional myosin
      isozymes in the inner ear, a tissue that is particularly reliant on actin-rich
      structures and unconventional myosin isozymes. Of the four isozymes, each from a
      different class, three are expressed in the hair cells of amphibia and mammals.
      In stereocilia, constructed of cross-linked F-actin filaments, myosin-Ibeta is
      found mostly near stereociliary tips, myosin-VI is largely absent, and myosin
      VIIa colocalizes with crosslinks that connect adjacent stereocilia. In the
      cuticular plate, a meshwork of actin filaments, myosin-Ibeta is excluded, myosin
      VI is concentrated, and modest amounts of myosin-VIIa are present. These three
      myosin isozymes are excluded from other actin-rich domains, including the
      circumferential actin belt and the cortical actin network. A member of a fourth
      class, myosin-V, is not expressed in hair cells but is present at high levels in
      afferent nerve cells that innervate hair cells. Substantial amounts of myosins
      Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely
      free of F-actin, squeezed between (but not associated with) actin of the
      cuticular plate and the circumferential belt. Our localization results suggest
      specific functions for three hair-cell myosin isozymes. As suggested previously,
      myosin-Ibeta probably plays a role in adaptation; concentration of myosin-VI in
      cuticular plates and association with stereociliary rootlets suggest that this
      isozyme participates in rigidly anchoring stereocilia; and finally,
      colocalization with cross-links between adjacent stereocilia indicates that
      myosin-VIIa is required for the structural integrity of hair bundles.

PMID- 9182665
TI  - Spindle dynamics during meiosis in Drosophila oocytes.
AB  - Mature oocytes of Drosophila are arrested in metaphase of meiosis I. Upon
      activation by ovulation or fertilization, oocytes undergo a series of rapid
      changes that have not been directly visualized previously. We report here the use
      of the Nonclaret disjunctional (Ncd) microtubule motor protein fused to the green
      fluorescent protein (GFP) to monitor changes in the meiotic spindle of live
      oocytes after activation in vitro. Meiotic spindles of metaphase-arrested oocytes
      are relatively stable, however, meiotic spindles of in vitro-activated oocytes
      are highly dynamic: the spindles elongate, rotate around their long axis, and
      undergo an acute pivoting movement to reorient perpendicular to the oocyte
      surface. Many oocytes spontaneously complete the meiotic divisions, permitting
      visualization of progression from meiosis I to II. The movements of the spindle
      after oocyte activation provide new information about the dynamic changes in the
      spindle that occur upon re-entry into meiosis and completion of the meiotic
      divisions. Spindles in live oocytes mutant for a loss-of-function ncd allele
      fused to gfp were also imaged. The genesis of spindle defects in the live mutant
      oocytes provides new insights into the mechanism of Ncd function in the spindle
      during the meiotic divisions.

PMID- 9182667
TI  - Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is
      concentrated in the cortical cytomatrix of axon initial segments and nodes of
      ranvier in brain and around T tubules in skeletal muscle.
AB  - Amphiphysin (amphiphysin I), a dominant autoantigen in paraneoplastic Stiff-man
      syndrome, is a neuronal protein highly concentrated in nerve terminals, where it
      has a putative role in endocytosis. The yeast homologue of amphiphysin, Rvs167,
      has pleiotropic functions, including a role in endocytosis and in actin dynamics,
      suggesting that amphiphysin may also be implicated in the function of the
      presynaptic actin cytoskeleton. We report here the characterization of a second
      mammalian amphiphysin gene, amphiphysin II (SH3P9; BIN1), which encodes products
      primarily expressed in skeletal muscle and brain, as differentially spliced
      isoforms. In skeletal muscle, amphiphysin II is concentrated around T tubules,
      while in brain it is concentrated in the cytomatrix beneath the plasmamembrane of
      axon initial segments and nodes of Ranvier. In both these locations, amphiphysin
      II is colocalized with splice variants of ankyrin3 (ankyrinG), a component of the
      actin cytomatrix. In the same regions, the presence of clathrin has been
      reported. These findings support the hypothesis that, even in mammalian cells,
      amphiphysin/Rvs family members have a role both in endocytosis and in actin
      function and suggest that distinct amphiphysin isoforms contribute to define
      distinct domains of the cortical cytoplasm. Since amphiphysin II (BIN1) was
      reported to interact with Myc, it may also be implicated in a signaling pathway
      linking the cortical cytoplasm to nuclear function.

PMID- 9182666
TI  - Fission yeast dim1(+) encodes a functionally conserved polypeptide essential for
      mitosis.
AB  - In a screen for second site mutations capable of reducing the restrictive
      temperature of the fission yeast mutant cdc2-D217N, we have isolated a novel
      temperature-sensitive mutant, dim1-35. When shifted to restrictive temperature,
      dim1-35 mutant cells arrest before entry into mitosis or proceed through mitosis
      in the absence of nuclear division, demonstrating an uncoupling of proper DNA
      segregation from other cell cycle events. Deletion of dim1 from the
      Schizosaccharomyces pombe genome produces a lethal G2 arrest phenotype. Lethality
      is rescued by overexpression of the mouse dim1 homolog, mdim1. Likewise, deletion
      of the Saccharomyces cerevisiae dim1 homolog, CDH1, is lethal. Both mdim1 and
      dim1(+) are capable of rescuing lethality in the cdh1::HIS3 mutant. Although dim1
      35 displays no striking genetic interactions with various other G2/M or mitotic
      mutants, dim1-35 cells incubated at restrictive temperature arrest with low
      histone H1 kinase activity. Morevoer, dim1-35 displays sensitivity to the
      microtubule destabilizing drug, thiabendazole (TBZ). We conclude that Dim1p plays
      a fundamental, evolutionarily conserved role as a protein essential for entry
      into mitosis as well as for chromosome segregation during mitosis. Based on TBZ
      sensitivity and failed chromosome segregation in dim1-35, we further speculate
      that Dim1p may play a role in mitotic spindle formation and/or function.

PMID- 9182668
TI  - Survival of Trypanosoma brucei in the tsetse fly is enhanced by the expression of
      specific forms of procyclin.
AB  - African trypanosomes are not passively transmitted, but they undergo several
      rounds of differentiation and proliferation within their intermediate host, the
      tsetse fly. At each stage, the survival and successful replication of the
      parasites improve their chances of continuing the life cycle, but little is known
      about specific molecules that contribute to these processes. Procyclins are the
      major surface glycoproteins of the insect forms of Trypanosoma brucei. Six genes
      encode proteins with extensive glutamic acid-proline dipeptide repeats (EP in the
      single-letter amino acid code), and two genes encode proteins with an internal
      pentapeptide repeat (GPEET). To study the function of procyclins, we have
      generated mutants that have no EP genes and only one copy of GPEET. This last
      gene could not be replaced by EP procyclins, and could only be deleted once a
      second GPEET copy was introduced into another locus. The EP knockouts are
      morphologically indistinguishable from the parental strain, but their ability to
      establish a heavy infection in the insect midgut is severely compromised; this
      phenotype can be reversed by the reintroduction of a single, highly expressed EP
      gene. These results suggest that the two types of procyclin have different roles,
      and that the EP form, while not required in culture, is important for survival in
      the fly.

PMID- 9182669
TI  - Proteolytic pathways of activation and degradation of a bacterial phospholipase C
      during intracellular infection by Listeria monocytogenes.
AB  - Listeria monocytogenes is a facultative intracellular bacterial pathogen that
      spreads cell to cell without exposure to the extracellular environment. Bacterial
      cell-to-cell spread is mediated in part by two secreted bacterial phospholipases
      C (PLC), a broad spectrum PLC (PC-PLC) and a phosphatidylinositolspecific PLC (PI
      PLC). PI-PLC is secreted in an active state, whereas PC-PLC is secreted as an
      inactive proenzyme (proPC-PLC) whose activation is mediated in vitro by an L.
      monocytogenes metalloprotease (Mpl). Analysis of PI-PLC, PC-PLC, and Mpl single
      and double mutants revealed that Mpl also plays a role in the spread of an
      infection, but suggested that proPC-PLC has an Mpl-independent activation
      pathway. Using biochemical and microscopic approaches, we describe three
      intracellular proteolytic pathways regulating PCPLC activity. Initially, proPC
      PLC secreted in the cytosol of infected cells was rapidly degraded in a
      proteasome-dependent manner. Later during infection, PCPLC colocalized with
      bacteria in lysosome-associated membrane protein 1-positive vacuoles. Activation
      of proPC-PLC in vacuoles was mediated by Mpl and an Mpl-independent pathway, the
      latter being sensitive to inhibitors of cysteine proteases. Lastly, proPC-PLC
      activation by either pathway was sensitive to bafilomycin A1, a specific
      inhibitor of vacuolar ATPase, suggesting that activation was dependent on
      acidification of the vacuolar compartment. These results are consistent with a
      model in which proPC-PLC activation is compartment specific and controlled by a
      combination of bacterial and host factors.

PMID- 9182670
TI  - Possible involvement of phosphorylation of occludin in tight junction formation.
AB  - Occludin is an integral membrane protein localizing at tight junctions in
      epithelial and endothelial cells. Occludin from confluent culture MDCK I cells
      resolved as several (>10) bands between 62 and 82 kD in SDS-PAGE, of which two or
      three bands of the lowest Mr were predominant. Among these bands, the lower
      predominant bands were essentially extracted with 1% NP-40, whereas the other
      higher Mr bands were selectively recovered in the NP-40-insoluble fraction.
      Alkaline phosphatase treatment converged these bands of occludin both in NP-40
      soluble and -insoluble fractions into the lowest Mr band, and phosphoamino acid
      analyses identified phosphoserine (and phosphothreonine weakly) in the higher Mr
      bands of occludin. These findings indicated that phosphorylation causes an upward
      shift of occludin bands and that highly phosphorylated occludin resists NP-40
      extraction. When cells were grown in low Ca medium, almost all occludin was NP-40
      soluble. Switching from low to normal Ca medium increased the amount of NP-40
      insoluble occludin within 10 min, followed by gradual upward shift of bands. This
      insolubilization and the band shift correlated temporally with tight junction
      formation detected by immunofluorescence microscopy. Furthermore, we found that
      the anti-chicken occludin mAb, Oc-3, did not recognize the predominant lower Mr
      bands of occludin (non- or less phosphorylated form) but was specific to the
      higher Mr bands (phosphorylated form) on immunoblotting. Immunofluorescence
      microscopy revealed that this mAb mainly stained the tight junction proper of
      intestinal epithelial cells, whereas other anti-occludin mAbs, which can
      recognize the predominant lower Mr bands, labeled their basolateral membranes
      (and the cytoplasm) as well as tight junctions. Therefore, we conclude that non-
      or less phosphorylated occludin is distributed on the basolateral membranes and
      that highly phosphorylated occludin is selectively concentrated at tight juctions
      as the NP-40-insoluble form. These findings suggest that the phosphorylation of
      occludin is a key step in tight junction assembly.

PMID- 9182671
TI  - The zinc-finger protein slug causes desmosome dissociation, an initial and
      necessary step for growth factor-induced epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is an essential morphogenetic process
      during embryonic development. It can be induced in vitro by hepatocyte growth
      factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We
      tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA
      and protein levels were increased transiently in FGF-1-treated NBT-II cells.
      Transient or stable transfection of Slug cDNA in NBT-II cells resulted in a
      striking disappearance of the desmosomal markers desmoplakin and desmoglein from
      cell-cell contact areas, mimicking the initial steps of FGF-1 or HGF/SF- induced
      EMT. Stable transfectant cells expressed Slug protein and were less epithelial,
      with increased cell spreading and cell-cell separation in subconfluent cultures.
      Interestingly, NBT-II cells transfected with antisense Slug cDNA were able to
      resist EMT induction by FGF-1 or even HGF/SF. This antisense effect was
      suppressed by retransfection with Slug sense cDNA. Our results indicate that Slug
      induces the first phase of growth factor-induced EMT, including desmosome
      dissociation, cell spreading, and initiation of cell separation. Moreover, the
      antisense inhibition experiments suggest that Slug is also necessary for EMT.

PMID- 9182672
TI  - The small GTPases Rho and Rac are required for the establishment of cadherin
      dependent cell-cell contacts.
AB  - Cadherins are calcium-dependent cell-cell adhesion molecules that require the
      interaction of the cytoplasmic tail with the actin cytoskeleton for adhesive
      activity. Because of the functional relationship between cadherin receptors and
      actin filament organization, we investigated whether members of the Rho family of
      small GTPases are necessary for cadherin adhesion. In fibroblasts, the Rho family
      members Rho and Rac regulate actin polymerization to produce stress fibers and
      lamellipodia, respectively. In epithelial cells, we demonstrate that Rho and Rac
      are required for the establishment of cadherin-mediated cell-cell adhesion and
      the actin reorganization necessary to stabilize the receptors at sites of
      intercellular junctions. Blocking endogenous Rho or Rac selectively removed
      cadherin complexes from junctions induced for up to 3 h, while desmosomes were
      not perturbed. In addition, withdrawal of cadherins from intercellular junctions
      temporally precedes the removal of CD44 and integrins, other microfilament
      associated receptors. Our data showed that the concerted action of Rho and Rac
      modulate the establishment of cadherin adhesion: a constitutively active form of
      Rac was not sufficient to stabilize cadherindependent cell-cell contacts when
      endogenous Rho was inhibited. Upon induction of calcium-dependent intercellular
      adhesion, there was a rapid accumulation of actin at sites of cell-cell contacts,
      which was prevented by blocking cadherin function, Rho or Rac activity. However,
      if cadherin complexes are clustered by specific antibodies attached to beads,
      actin recruitment to the receptors was perturbed by inhibiting Rac but not Rho.
      Our results provide new insights into the role of the small GTPases in the
      cadherin-dependent cell- cell contact formation and the remodelling of actin
      filaments in epithelial cells.

PMID- 9182673
TI  - Affinity modulation of platelet integrin alphaIIbbeta3 by beta3-endonexin, a
      selective binding partner of the beta3 integrin cytoplasmic tail.
AB  - Platelet agonists increase the affinity state of integrin alphaIIbbeta3, a
      prerequisite for fibrinogen binding and platelet aggregation. This process may be
      triggered by a regulatory molecule(s) that binds to the integrin cytoplasmic
      tails, causing a structural change in the receptor. beta3-Endonexin is a novel
      111-amino acid protein that binds selectively to the beta3 tail. Since beta3
      endonexin is present in platelets, we asked whether it can affect alphaIIbbeta3
      function. When beta3-endonexin was fused to green fluorescent protein (GFP) and
      transfected into CHO cells, it was found in both the cytoplasm and the nucleus
      and could be detected on Western blots of cell lysates. PAC1, a fibrinogen
      mimetic mAb, was used to monitor alphaIIbbeta3 affinity state in transfected
      cells by flow cytometry. Cells transfected with GFP and alphaIIbbeta3 bound
      little or no PAC1. However, those transfected with GFP/beta3-endonexin and
      alphaIIbbeta3 bound PAC1 specifically in an energy-dependent fashion, and they
      underwent fibrinogen-dependent aggregation. GFP/beta3-endonexin did not affect
      levels of surface expression of alphaIIbbeta3 nor did it modulate the affinity of
      an alphaIIbbeta3 mutant that is defective in binding to beta3-endonexin. Affinity
      modulation of alphaIIbbeta3 by GFP/beta3-endonexin was inhibited by coexpression
      of either a monomeric beta3 cytoplasmic tail chimera or an activated form of H
      Ras. These results demonstrate that beta3-endonexin can modulate the affinity
      state of alphaIIbbeta3 in a manner that is structurally specific and subject to
      metabolic regulation. By analogy, the adhesive function of platelets may be
      regulated by such protein-protein interactions at the level of the cytoplasmic
      tails of alphaIIbbeta3.

PMID- 9182674
TI  - The activity of collagenase-1 is required for keratinocyte migration on a type I
      collagen matrix.
AB  - We have shown in a variety of human wounds that collagenase-1 (MMP-1), a matrix
      metalloproteinase that cleaves fibrillar type I collagen, is invariably expressed
      by basal keratinocytes migrating across the dermal matrix. Furthermore, we have
      demonstrated that MMP-1 expression is induced in primary keratinocytes by contact
      with native type I collagen and not by basement membrane proteins or by other
      components of the dermal or provisional (wound) matrix. Based on these
      observations, we hypothesized that the catalytic activity of MMP-1 is necessary
      for keratinocyte migration on type I collagen. To test this idea, we assessed
      keratinocyte motility on type I collagen using colony dispersion and colloidal
      gold migration assays. In both assays, primary human keratinocytes migrated
      efficiently on collagen. The specificity of MMP-1 in promoting cell movement was
      demonstrated in four distinct experiments. One, keratinocyte migration was
      completely blocked by peptide hydroxymates, which are potent inhibitors of the
      catalytic activity of MMPs. Two, HaCaTs, a line of human keratinocytes that do
      not express MMP-1 in response to collagen, did not migrate on a type I collagen
      matrix but moved efficiently on denatured type I collagen (gelatin). EGF, which
      induces MMP-I production by HaCaT cells, resulted in the ability of these cells
      to migrate across a type I collagen matrix. Three, keratinocytes did not migrate
      on mutant type I collagen lacking the collagenase cleavage site, even though this
      substrate induced MMP-1 expression. Four, cell migration on collagen was
      completely blocked by recombinant tissue inhibitor of metalloproteinase-1 (TIMP
      1) and by affinity-purified anti-MMP-1 antiserum. In addition, the collagen
      mediated induction of collagenase-1 and migration of primary keratinocytes on
      collagen was blocked by antibodies against the alpha2 integrin subunit but not by
      antibodies against the alpha1 or alpha3 subunits. We propose that interaction of
      the alpha2beta1 integrin with dermal collagen mediates induction of collagenase-1
      in keratinocytes at the onset of healing and that the activity of collagenase-1
      is needed to initiate cell movement. Furthermore, we propose that cleavage of
      dermal collagen provides keratinocytes with a mechanism to maintain their
      directionality during reepithelialization.

PMID- 9182675
TI  - HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from
      beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double
      knockout mice.
AB  - Three different HLA-A2.1 monochains were engineered in which either the human or
      mouse beta2-microglobulin (beta2m) is covalently linked to the NH2 terminus of
      the heavy chain by a 15- amino acid long peptide: HHH, entirely human, HHD, with
      the mouse H-2Db alpha3, transmembrane, and cytoplasmic domains, and MHD,
      homologous to HHD but linked to the mouse beta2mb. The cell surface expression
      and immunological capacities of the three monochains were compared with
      transfected cells, and the selected HHD construct was introduced by transgenesis
      in H-2Db-/- beta2m-/- double knockout mice. Expression of this monochain restores
      a sizable peripheral CD8(+) T cell repertoire essentially educated on the
      transgenic human molecule. Consequently, infected HHD, H-2Db-/- beta2m-/- mice
      generate only HLA-A2.1-restricted CD8(+) CTL responses against influenza A and
      vaccinia viruses. Interestingly, the CTL response to influenza A virus is mostly,
      if not exclusively, directed to the 58-66 matrix peptide which is the HLA-A2.1
      restricted immunodominant epitope in humans. Such mice might constitute a
      versatile animal model for the study of HLA-A2.1-restricted CTL responses of
      vaccine interest.

PMID- 9182677
TI  - Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan.
AB  - Whereas amastigotes of the protozoan parasite Leishmania proliferate inside
      acidic phagolysosomal vacuoles of the macrophage, vacuoles induced by Leishmania
      donovani promastigotes during initiation of infection are poorly characterized.
      Here, evidence is presented that interaction of these parasitophorous vacuoles
      with endocytic organelles is very limited. In contrast, vacuoles formed around L.
      donovani mutants lacking the cell surface lipophosphoglycan (LPG) fuse
      extensively with endosomes and lysosomes. The role of LPG repeating units in the
      inhibition of phagosome-endosome fusion was demonstrated using two different
      approaches. First, genetic complementation of the LPG-defective C3PO mutant
      restored its ability to inhibit phagosome-endosome fusion to a degree similar to
      that of wild-type promastigotes. Second, opsonization of C3PO mutant cells with
      purified L. donovani LPG also conferred to this mutant the ability to inhibit
      phagosome-endosome fusion. Inasmuch as LPG is essential for infecting
      macrophages, these results suggest that inhibition of phagolysosomal biogenesis
      by LPG repeating units represents an intramacrophage survival strategy used by
      promastigotes to establish infection.

PMID- 9182676
TI  - A new mechanism of NK cell cytotoxicity activation: the CD40-CD40 ligand
      interaction.
AB  - NK recognition is regulated by a delicate balance between positive signals
      initiating their effector functions, and inhibitory signals preventing them from
      proceeding to cytolysis. Knowledge of the molecules responsible for positive
      signaling in NK cells is currently limited. We demonstrate that IL-2-activated
      human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on
      target cells can provide an activation pathway for such human NK cells. CD40
      transfected P815 cells were killed by NK cell lines expressing CD40L, clones and
      PBL-derived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L
      negative fresh NK cells. Cross-linking of CD40L on IL-2-activated NK cells
      induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815
      cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti
      CD40 antibodies as well as by reconstitution of TAP/MHC class I expression,
      indicating that the CD40-dependent pathway for NK activation can be
      downregulated, at least in part, by MHC class I molecules on the target cells. NK
      cell recognition of CD40 may be important in immunoregulation as well as in
      immune responses against B cell malignancies.

PMID- 9182678
TI  - Novel vascular molecule involved in monocyte adhesion to aortic endothelium in
      models of atherogenesis.
AB  - Adhesion of monocytes to the endothelium in lesion-prone areas is one of the
      earliest events in fatty streak formation leading to atherogenesis. The molecular
      basis of increased monocyte adhesion is not fully characterized. We have
      identified a novel vascular monocyte adhesion-associated protein, VMAP-1, that
      plays a role in adhesion of monocytes to activated endothelium. Originally
      selected for its ability to block binding of a mouse monocyte-like cell line
      (WEHI78/24) to cytokine- or LPS-stimulated cultured mouse endothelial cells in
      vitro, antiVMAP-1 mAb LM151 cross-reacts with rabbit endothelium and blocks
      binding of human monocytes to cultured rabbit aortic endothelial cells stimulated
      with minimally modified low density lipoprotein, thought to be a physiologically
      relevant atherogenic stimulus. Most importantly, LM151 prevents adhesion of
      normal monocytes and monocytoid cells to intact aortic endothelium from
      cholesterol-fed rabbits in an ex vivo assay. VMAP-1 is a 50-kD protein.
      Immunohistology of vessels reveals focal constitutive expression in aorta and
      other large vessels. VMAP-1 is thus a novel vascular adhesion-associated protein
      that appears to play a critical role in monocyte adhesion to aortic endothelial
      cells in atherogenesis in vivo.

PMID- 9182679
TI  - Ly49A transgenic mice provide evidence for a major histocompatibility complex
      dependent education process in natural killer cell development.
AB  - The Ly49 natural killer (NK) cell receptors are class I MHC-specific inhibitory
      receptors that are distributed to overlapping NK cell subsets. The formation of
      the Ly49 receptor repertoire was examined with transgenic mice that express Ly49A
      in all NK cells. In MHC class I-deficient mice, the Ly49A transgene did not
      prevent expression of endogenous Ly49 genes. However, in H-2(d) mice that express
      a Ly49A ligand, the transgene caused clear alterations in the endogenous Ly49
      repertoire. The frequency of NK cells expressing another H-2(d)-specific
      receptor, Ly49G2(+), was substantially reduced. Reduced numbers of cells
      expressing endogenous Ly49A was suggested by reduced endogenous Ly49A mRNA
      levels. These results support the existence of an MHC-dependent education process
      that limits the number of NK cells that coexpress multiple self-specific Ly49
      receptors. Ligand-dependent downregulation of Ly49 cell surface levels was also
      examined. Cell-surface downregulation occurred even when the transgene was
      expressed at low levels. The results demonstrate that downregulation of Ly49A
      cell surface levels is a posttranscriptional event, and argue against a model in
      which Ly49 receptors are calibrated to specific cell surface levels depending on
      the available class I ligands.

PMID- 9182681
TI  - Mice genetically hyporesponsive to lipopolysaccharide (LPS) exhibit a defect in
      endocytic uptake of LPS and ceramide.
AB  - We have recently shown that monomeric bacterial LPS is rapidly delivered from the
      plasma membrane to an intracellular site and that agents that block vesicular
      transport block responses of neutrophils to lipopolysaccharide (LPS) (Detmers,
      P.A., N. Thieblemont, T. Vasselon, R. Pironkova, D.S. Miller, and S.D. Wright.
      1996. J. Immunol. 157:5589-5596). To examine further the connection between
      intracellular transport of LPS and signaling, we observed internalization of
      fluorescently labeled LPS in cells from LPS-hyporesponsive (Lpsd) mice. Binding
      of fluorescent LPS from LPS-soluble CD14 (sCD14) complexes by peritoneal
      macrophages from Lpsd and control (Lpsn) mice was quantitatively similar, and
      confocal images obtained from these cells exhibited an identical appearance
      immediately after labeling. Incubation of labeled Lpsn macrophages at 37 degrees
      C caused movement of the fluorescence from the cell perimeter in one or two spots
      in the perinuclear region. However, in Lpsd cells the fluorescence remained
      dispersed, suggesting a defect in vesicular transport. LPS resembles ceramide,
      and Lpsd mice fail to respond to ceramide. As with LPS, we found that binding of
      fluorescent ceramide by Lpsd and Lpsn macrophages was quantitatively similar, and
      the label moved rapidly to one to two spots in the perinuclear region in Lpsn
      mice. However, in Lpsd macrophages the fluorescence remained dispersed. These
      results show that cells deficient in responses to LPS exhibit defective vesicular
      transport of LPS and ceramide and point to a role for vesicular transport in
      responses to these mediators.

PMID- 9182680
TI  - T cell stimulation in vivo by lipopolysaccharide (LPS).
AB  - Lipopolysaccharide (LPS) from gram-negative bacteria causes polyclonal activation
      of B cells and stimulation of macrophages and other APC. We show here that, under
      in vivo conditions, LPS also induces strong stimulation of T cells. As manifested
      by CD69 upregulation, LPS injection stimulates both CD4 and CD8(+) T cells, and,
      at high doses, stimulates naive (CD44(lo)) cells as well as memory (CD44(hi))
      cells. However, in terms of cell division, the response of T cells after LPS
      injection is limited to the CD44(hi) subset of CD8(+) cells. In contrast with B
      cells, proliferative responses of CD44(hi) CD8(+) cells require only very low
      doses of LPS (10 ng). Based on studies with LPS-nonresponder and gene-knockout
      mice, LPS-induced proliferation of CD44(hi) CD8(+) cells appears to operate via
      an indirect pathway involving LPS stimulation of APC and release of type I
      (alpha, beta) interferon (IFN-I). Similar selective stimulation of CD44(hi)
      CD8(+) cells occurs in viral infections and after injection of IFN-I, implying a
      common mechanism. Hence, intermittent exposure to pathogens (gram-negative
      bacteria and viruses) could contribute to the high background proliferation of
      memory-phenotype CD8(+) cells found in normal animals.

PMID- 9182682
TI  - Altered immune responses in interleukin 10 transgenic mice.
AB  - Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of
      immune parameters including T helper cell type 1 (Th1) cytokine production,
      antigen presentation, and antigen-specific T cell proliferation. To understand
      the consequences of altered expression of IL-10 in immune models of autoimmune
      disease, the response to infectious agents, and the response to tumors, we
      developed transgenic mice expressing IL-10 under the control of the IL-2
      promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic
      mice secrete higher levels of IL-10 and lower amounts of IFN-gamma than do
      controls, although no gross abnormalities were detected in lymphocyte populations
      or serum Ig levels. Transfer of normally pathogenic CD4(+) CD45RBhigh splenic T
      cells from IL-10 transgenic mice did not cause colitis in recipient severe
      combined immunodeficiency mice. Furthermore, co-transfer of these transgenic
      cells with CD4(+) CD45RBhigh T cells from control mice prevented disease.
      Transgenic mice retained their resistance to Leishmania major infection,
      indicating that their cell-mediated immune responses were not globally
      suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable
      to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs
      restored in vivo antitumor responses in the transgenic mice. These results
      demonstrate that a single alteration in the T cell cytokine profile can lead to
      dramatic changes in immune responses in a manner that is stimulus dependent.
      These mice will be useful in defining differences in inflammatory conditions and
      cellular immunity mediated by IL-10.

PMID- 9182683
TI  - Lymphotoxin-alpha (LTalpha) supports development of splenic follicular structure
      that is required for IgG responses.
AB  - LTalpha-deficient (LTalpha-/-) mice show altered splenic microarchitecture. This
      includes loss of normal B cell-T cell compartmentalization, of follicular
      dendritic cell (FDC) clusters, and of ability to form germinal centers (GC).
      LTalpha-/- mice immunized with sheep red blood cells (SRBC) produced high levels
      of antigen-specific IgM but no IgG in either primary or secondary responses,
      demonstrating failure of Ig class switching. This inability to switch to IgG
      could have been due to the altered splenic microarchitecture in these mice.
      Alternatively, it could have been due directly to a requirement for LTalpha
      expression by lymphocytes cooperating in the antibody response. To investigate
      this, we performed reciprocal spleen cell transfers. When irradiated LTalpha-/-
      mice were reconstituted with wild-type splenocytes and immunized immediately with
      SRBC, splenic microarchitecture remained disturbed and there was no IgG response.
      In contrast, when irradiated wild-type animals received splenocytes from LTalpha
      /- mice, follicle structure and a strong IgG response were retained. These data
      indicate that LTalpha-deficient B cells and T cells have no intrinsic defect in
      ability to generate an IgG response. Rather, the altered microenvironment
      characteristic of LTalpha-/- mice appears to result in impaired ability to switch
      to a productive IgG response. To investigate whether prolonged expression of
      LTalpha could alter the structure and function of spleen follicles, reciprocal
      bone marrow (BM) transplantation was performed. Six weeks after reconstitution of
      LTalpha-/- mice with wild-type BM, spleen follicle structure was partially
      restored, with return of FDC clusters and GC. B cell/T cell compartmentalization
      remained abnormal and white pulp zones were small. This was accompanied by
      restoration of IgG response to SRBC. Reconstitution of wild-type mice with
      LTalpha-/- BM resulted in loss of FDC clusters and GC, and loss of the IgG
      response, although compartmentalized B cell and T cell zones were largely
      retained. Thus, defective IgG production is not absolutely associated with
      abnormal B cell and T cell compartmentalization. Rather, expression of LTalpha
      supports the maturation of spleen follicle structure, including the development
      and maintenance of FDC clusters, which supports Ig class switching and an
      effective IgG response.

PMID- 9182684
TI  - Paracrine regulation of germinal center B cell adhesion through the c-met
      hepatocyte growth factor/scatter factor pathway.
AB  - T cell-dependent humoral immune responses are initiated by the activation of
      naive B cells in the T cell areas of the secondary lymphoid tissues. This primary
      B cell activation leads to migration of germinal center (GC) cell precursors into
      B cell follicles where they engage follicular dendritic cells (FDC) and T cells,
      and differentiate into memory B cells or plasma cells. Both B cell migration and
      interaction with FDC critically depend on integrin-mediated adhesion. To date,
      the physiological regulators of this adhesion were unkown. In the present report,
      we have identified the c-met-encoded receptor tyrosine kinase and its ligand, the
      growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF), as a
      novel paracrine signaling pathway regulating B cell adhesion. We observed that c
      Met is predominantly expressed on CD38(+)CD77(+) tonsillar B cells localized in
      the dark zone of the GC (centroblasts). On tonsil B cells, ligation of CD40 by
      CD40-ligand, induces a transient strong upregulation of expression of the c-Met
      tyrosine kinase. Stimulation of c-Met with HGF/SF leads to receptor
      phosphorylation and, in addition, to enhanced integrin-mediated adhesion of B
      cells to both VCAM-1 and fibronectin. Importantly, the c-Met ligand HGF/SF is
      produced at high levels by tonsillar stromal cells thus providing signals for the
      regulation of adhesion and migration within the lymphoid microenvironment.

PMID- 9182685
TI  - In vivo detection of dendritic cell antigen presentation to CD4(+) T cells.
AB  - Although lymphoid dendritic cells (DC) are thought to play an essential role in T
      cell activation, the initial physical interaction between antigen-bearing DC and
      antigen-specific T cells has never been directly observed in vivo under
      conditions where the specificity of the responding T cells for the relevant
      antigen could be unambiguously assessed. We used confocal microscopy to track the
      in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4(+) T
      cells specific for an OVA peptide-I-Ad complex after adoptive transfer into
      syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the
      paracortical regions of the lymph nodes but did not interact with the OVA peptide
      specific T cells. In contrast, the OVA peptide-specific T cells formed large
      clusters around paracortical DC that were pulsed in vitro with the OVA peptide
      before injection. Interactions were also observed between paracortical DC of the
      recipient and OVA peptide-specific T cells after administration of intact OVA.
      Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in
      vivo, proliferate, and differentiate into effector cells capable of causing a
      delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection,
      OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice
      that contained the transferred TCR transgenic population. These results
      demonstrate that antigen-bearing DC directly interact with naive antigen-specific
      T cells within the T cell-rich regions of lymph nodes. This interaction results
      in T cell activation and disappearance of the DC.

PMID- 9182686
TI  - Interleukin-5 expression in the lung epithelium of transgenic mice leads to
      pulmonary changes pathognomonic of asthma.
AB  - We have generated transgenic mice that constitutively express murine interleukin
      (IL)-5 in the lung epithelium. Airway expression of this cytokine resulted in a
      dramatic accumulation of peribronchial eosinophils and striking pathologic
      changes including the expansion of bronchus-associated lymphoid tissue (BALT),
      goblet cell hyperplasia, epithelial hypertrophy, and focal collagen deposition.
      These changes were also accompanied by eosinophil infiltration of the airway
      lumen. In addition, transgenic animals displayed airway hyperresponsiveness to
      methacholine in the absence of aerosolized antigen challenge. These findings
      demonstrate that lung-specific IL-5 expression can induce pathologic changes
      characteristic of asthma and may provide useful models to evaluate the efficacy
      of potential respiratory disease therapies or pharmaceuticals.

PMID- 9182687
TI  - On the key role of secondary lymphoid organs in antiviral immune responses
      studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice.
AB  - The role of the spleen and of other organized secondary lymphoid organs for the
      induction of protective antiviral immune responses was evaluated in orphan
      homeobox gene 11 knockout mice (Hox11(-/-)) lacking the spleen, and in homozygous
      alymphoplastic mutant mice (aly/aly) possessing a structurally altered spleen but
      lacking lymph nodes and Peyer's patches. Absence of the spleen had no major
      effects on the immune response, other than delaying the antibody response by 1-2
      d. In aly/aly mice, the thymus-independent IgM response against vesicular
      stomatitis virus (VSV) was delayed and reduced, whereas the T-dependent switch to
      the protective IgG was absent. Therefore, aly/aly mice were highly susceptible to
      VSV infection. Since aly/aly spleen cells yielded neutralizing IgM and IgG after
      adoptive transfer into recipients with normally structured secondary lymphoid
      organs, these data suggest that the structural defect was mainly responsible for
      inefficient T-B cooperation. Although aly/aly mice generated detectable, but
      reduced, CTL responses after infection with vaccinia virus (VV) and lymphocytic
      choriomeningitis virus (LCMV), the elimination of these viruses was either
      delayed (VV) or virtually impossible (LCMV); irrespective of the dose or the
      route of infection, aly/aly mice developed life-long LCMV persistence. These
      results document the critical role of organized secondary lymphoid organs in the
      induction of naive T and B cells. These structures also provide the basis for
      cooperative interactions between antigen-presenting cells, T cells, and B cells,
      which are a prerequisite for recovery from primary virus infections via skin or
      via blood.

PMID- 9182688
TI  - Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor
      CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes.
AB  - A novel human CC chemokine consisting of 78 amino acids and having a molecular
      mass of 8,778.3 daltons (VVIPSPCCMF FVSKRIPENR VVSYQLSSRS TCLKAGVIFT TKKGQQ SCGD
      PKQEWVQRYM KNLDAKQKKA SPRARAVA) was isolated together with three minor COOH
      terminally truncated variants with 73, 75, and 76 residues. The new chemokine was
      termed eotaxin-2 because it is functionally very similar to eotaxin. In terms of
      structure, however, eotaxin and eotaxin-2 are rather distant, they share only 39%
      identical amino acids and differ almost completely in the NH2-terminal region.
      Eotaxin-2 induced chemotaxis of eosinophils as well as basophils, with a
      typically bimodal concentration dependence, and the release of histamine and
      leukotriene C4 from basophils that had been primed with IL-3. In all assays,
      eotaxin-2 had the same efficacy as eotaxin, but was somewhat less potent. The
      migration and the release responses were abrogated in the presence of a
      monoclonal antibody that selectively blocks the eotaxin receptor, CCR3,
      indicating that eotaxin-2, like eotaxin, acts exclusively via CCR3. Receptor
      usage was also studied in desensitization experiments by measuring [Ca2+]i
      changes in eosinophils. Complete cross-desensitization was observed between
      eotaxin-2, eotaxin and MCP-4 confirming activation via CCR3. No Ca2+ mobilization
      was obtained in neutrophils, monocytes and lymphocytes, in agreement with the
      lack of chemotactic responsiveness. Intradermal injection of eotaxin-2 in a
      rhesus monkey (100 or 1,000 pmol per site) induced a marked local infiltration of
      eosinophils, which was most pronounced in the vicinity of postcapillary venules
      and was comparable to the effect of eotaxin.

PMID- 9182689
TI  - Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction
      of acute experimental autoimmune encephalomyelitis.
AB  - Immunization of mice with myelin components results in experimental autoimmune
      encephalomyelitis (EAE), which is mediated by myelin-specific CD4(+) T cells and
      anti-myelin antibodies. Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin
      alpha (LT-alpha) are thought to be involved in the events leading to inflammatory
      demyelination in the central nervous system. To ascertain this hypothesis 129 x
      C57BL/6 mice with an inactivation of the tnf and lta genes (129 x C57BL/6(-/-))
      and SJL/J mice derived from backcrosses of the above mentioned mutant mice (SJL-/
      ) were immunized with mouse spinal cord homogenate (MSCH) or proteolipid protein.
      Both 129 x C57BL/6(-/-) mice and SJL-/- mice developed EAE. In SJL-/- mice
      immunized with MSCH, a very severe form of EAE with weight loss, paralysis of all
      four limbs, and lethal outcome was observed. The histologic hallmark was an
      intense perivascular and parenchymal infiltration with predominantly CD4(+) T
      cells and some CD8(+) T cells associated with demyelination in both brain and
      spinal cord. These results indicate that TNF-alpha and LT-alpha are not essential
      for the development of EAE.

PMID- 9182691
TI  - Activation of pro-caspase-7 by serine proteases includes a non-canonical
      specificity.
AB  - As a model to investigate the mechanism of caspase activation we have analysed
      the processing of pro-caspase-7 by serine proteases with varied specificities.
      The caspase-7 zymogen was rapidly activated by granzyme B and more slowly by
      subtilisin and cathepsin G, generating active enzymes with similar kinetic
      properties. Significantly, cathepsin G activated the zymogen by cleaving at a Gln
      Ala bond, indicating that the canonical cleavage specificity at aspartic acid is
      not required for activation.

PMID- 9182690
TI  - Phospholipid transfer proteins revisited.
AB  - Phosphatidylinositol transfer protein (PI-TP) and the non-specific lipid transfer
      protein (nsL-TP) (identical with sterol carrier protein 2) belong to the large
      and diverse family of intracellular lipid-binding proteins. Although these two
      proteins may express a comparable phospholipid transfer activity in vitro, recent
      studies in yeast and mammalian cells have indicated that they serve completely
      different functions. PI-TP (identical with yeast SEC14p) plays an important role
      in vesicle flow both in the budding reaction from the trans-Golgi network and in
      the fusion reaction with the plasma membrane. In yeast, vesicle budding is linked
      to PI-TP regulating Golgi phosphatidylcholine (PC) biosynthesis with the apparent
      purpose of maintaining an optimal PI/PC ratio of the Golgi complex. In mammalian
      cells, vesicle flow appears to be dependent on PI-TP stimulating
      phosphatidylinositol 4,5-bisphosphate (PIP2) synthesis. This latter process may
      also be linked to the ability of PI-TP to reconstitute the receptor-controlled
      PIP2-specific phospholipase C activity. The nsL-TP is a peroxisomal protein
      which, by its ability to bind fatty acyl-CoAs, is most likely involved in the
      beta-oxidation of fatty acids in this organelle. This protein constitutes the N
      terminus of the 58 kDa protein which is one of the peroxisomal 3-oxo-acyl-CoA
      thiolases. Further studies on these and other known phospholipid transfer
      proteins are bound to reveal new insights in their important role as mediators
      between lipid metabolism and cell functions.

PMID- 9182692
TI  - Activation of mitogen-activated protein kinase and p70S6 kinase is not correlated
      with cerebellar granule cell survival.
AB  - We have investigated the role of mitogen-activated protein (MAP) kinase in the
      survival of cerebellar granule cells in primary culture. Brain-derived
      neurotrophic factor (BDNF) and insulin, but not epidermal growth factor (EGF),
      promoted the survival of P6 cerebellar granule neurons. BDNF promoted a sustained
      activation of MAP kinase, whereas that induced by EGF was only transient. Insulin
      promoted a small but transient activation of MAP kinase that was completely
      blocked by PD98059, an inhibitor of MAP kinase kinase activation. PD98059 had no
      effect on the insulin- or BDNF-induced survival of cerebellar granule cells. We
      also investigated the role of p70S6 kinase in survival. The activation of p70S6
      kinase by EGF was transient, whereas BDNF and insulin promoted a sustained
      activation of p70S6 kinase. Rapamycin, which blocked p70S6 kinase activation, had
      no effect on the BDNF- or insulin-induced survival of cerebellar granule cells.
      We conclude that sustained activation of MAP kinase is not correlated with the
      survival response of cerebellar granule cells; indeed insulin-mediated survival
      is independent of MAP kinase. Survival of cerebellar granule cells is also
      independent of the activation of p70S6 kinase.

PMID- 9182693
TI  - Synthesis and properties of the very-low-density-lipoprotein receptor and a
      comparison with the low-density-lipoprotein receptor.
AB  - The properties of the very-low-density lipoprotein (VLDL) receptor have been
      studied in Chinese hamster ovary (CHO) cells stably transfected with human VLDL
      receptor cDNA and compared with those of the low-density lipoprotein (LDL)
      receptor expressed under the same conditions. Immunoblotting showed that the
      cells produced a mature VLDL receptor protein, of apparent Mr 123000 on non
      reduced and 158000 on reduced gels, that was less extensively glycosylated than
      the LDL receptor. The VLDL receptor was more slowly processed than the LDL
      receptor, with only approx. 70% of the precursor being converted into the mature
      protein. Nevertheless, the majority of the receptor in the cells was in the
      mature form, and most of this was present on the cell surface. The human VLDL
      receptor bound rabbit very-low-density lipoprotein with beta electrophoretic
      mobility (betaVLDL), but not human LDL, and uptake through the receptor led to
      stimulation of oleate incorporation into cholesteryl esters. At 37 degrees C, the
      characteristics of VLDL-receptor-mediated uptake and degradation of betaVLDL were
      essentially the same as those mediated by the LDL receptor. However, the VLDL
      receptor apparently did not show the increase in affinity and decrease in binding
      of betaVLDL on cooling to 4 degrees C that was exhibited by the LDL receptor.
      Thus the overexpressed VLDL receptor in CHO cells appears to behave as a
      lipoprotein receptor with similar, but not identical, properties to the LDL
      receptor.

PMID- 9182694
TI  - Interaction between cAMP-dependent and insulin-dependent signal pathways in
      tyrosine phosphorylation in primary cultures of rat hepatocytes.
AB  - The present studies were undertaken to determine whether the interaction between
      cAMP-dependent and insulin-dependent pathways in primary cultures of rat
      hepatocytes affects biological functions and tyrosine phosphorylation. Quiescent
      hepatocytes were pretreated with dibutyryl cAMP or cAMP-generating agents such as
      glucagon, and then treated or not with insulin. Preincubation for 6 h with
      dibutyryl cAMP or glucagon enhanced the effect of insulin on DNA synthesis, but
      not the effect of insulin on amino acid transport or glycogen and protein
      synthesis. Tyrosine phosphorylation of intracellular proteins was determined by
      immunoblot analysis using an anti-phosphotyrosine antibody. Maximum tyrosine
      phosphorylation of a 195 kDa protein, which may be a substrate of insulin
      receptor kinase, of 175-180 kDa proteins, including insulin receptor substrate
      (IRS)-1, and of 90-95 kDa proteins, including the insulin receptor beta-subunit,
      was reached within 30 s of incubation with insulin. Pretreatment for about 3 h
      with dibutyryl cAMP or cAMP-generating agents clearly increased insulin-dependent
      tyrosine phosphorylation of the 195 kDa protein, but not IRS-1, IRS-2 or the
      insulin receptor beta-subunit. Because dibutyryl cAMP and cAMP-generating agents
      did not increase insulin receptor number or its kinase activity, the effect of
      cAMP on this potentiation of tyrosine phosphorylation is assumed to be exerted at
      a step distal to insulin receptor kinase activation. The potentiation by cAMP
      pretreatment of insulin-stimulated tyrosine phosphorylation may in part be
      secondary to inhibition of phosphotyrosine phosphatase activity, because cAMP
      pretreatment blunted the effect of Na3VO4 on the net tyrosine phosphorylation of
      the 195 kDa protein as compared with cells pretreated with no additive. In
      summary, the interactions between cAMP-dependent and insulin-dependent pathways
      that lead to augmentation of DNA synthesis appear to parallel the changes in
      tyrosine phosphorylation. Further studies will be required to determine whether
      there is a causal relationship between these phenomena.

PMID- 9182696
TI  - Inactivation kinetics of dihydrofolate reductase from Chinese hamster during urea
      denaturation.
AB  - The kinetic theory of substrate reaction during modification of enzyme activity
      has been applied to the study of inactivation kinetics of Chinese hamster
      dihydrofolate reductase by urea [Tsou (1988) Adv. Enzymol. Relat. Areas Mol.
      Biol. 61, 381-436]. On the basis of the kinetic equation of substrate reaction in
      the presence of urea, all microscopic kinetic constants for the free enzyme and
      enzyme-substrate binary and ternary complexes have been determined. The results
      of the present study indicate that the denaturation of dihydrofolate reductase by
      urea follows single-phase kinetics, and changes in enzyme activity and tertiary
      structure proceed simultaneously in the unfolding process. Both substrates, NADPH
      and 7,8-dihydrofolate, protect dihydrofolate reductase against inactivation, and
      enzyme-substrate complexes lose their activity less rapidly than the free enzyme.

PMID- 9182695
TI  - Existence of two translation initiation sites leading to the expression of two
      proteins from the rat high-affinity neurotensin-receptor cDNA: possible
      regulation by the 5' end non-coding region.
AB  - This work demonstrates the expression of two different proteins (47 and 44 kDa)
      from the rat high-affinity neurotensin receptor cDNA, observed after both
      translation in vitro and transient transfection into eukaryotic COS-7 cells.
      These two proteins are the consequence of two initiation sites of translation
      present in the corresponding mRNA. Site-directed mutagenesis indicated that the
      47 kDa protein was generated from the first AUG codon (Met1). In contrast,
      suppression of the second AUG codon found in the sequence (Met27) did not modify
      the expression of the two proteins previously observed with the wild-type
      neurotensin receptor. Therefore this second translation site could correspond to
      a non-AUG codon. Moreover, when the 5' end untranslated region of the neurotensin
      receptor mRNA is deleted, the expression of the higher-molecular-mass protein is
      enhanced, indicating that this region could be involved in the regulation of
      expression of these two proteins.

PMID- 9182697
TI  - Two genes encoding an endoglucanase and a cellulose-binding protein are clustered
      and co-regulated by a TTA codon in Streptomyces halstedii JM8.
AB  - Streptomyces halstedii JM8 Cel2 is an endoglucanase of 28 kDa that is first
      produced as a protein of 42 kDa (p42) and is later processed at its C-terminus.
      Cel2 displays optimal activity towards CM-cellulose at pH6 and 50 degrees C and
      shows no activity against crystalline cellulose or xylan. The N-terminus of p42
      shares similarity with cellulases included in family 12 of the beta-glycanases
      and the C-terminus shares similarity with bacterial cellulose-binding domains
      included in family II. This latter domain enables the precursor to bind so
      tightly to Avicel that it can only be eluted by boiling in 10% (w/v) SDS. Another
      open reading frame (ORF) situated 216 bp downstream from the p42 ORF encodes a
      protein of 40 kDa (p40) that does not have any clear hydrolytic activity against
      cellulosic or xylanosic compounds, but shows high affinity for Avicel
      (crystalline cellulose). The p40 protein is processed in old cultures to give a
      protein of 35 kDa that does not bind to Avicel. Translation of both ORFs is
      impaired in Streptomyces coelicolor bldA mutants, suggesting that a TTA codon
      situated at the fourth position of the first ORF is responsible for this
      regulation. S1 nuclease protection experiments demonstrate that both ORFs are co
      transcribed.

PMID- 9182698
TI  - Resolution of two ADP-ribosylation factor 1 GTPase-activating proteins from rat
      liver.
AB  - ADP-ribosylation factor 1 (ARF1) is a 21 kDa GTP-binding protein that regulates
      multiple steps in membrane traffic. Here, two ARF1 GTPase-activating proteins
      (GAPs) from rat liver were resolved. The GAPs were antigenically distinct. One
      reacted with a polyclonal antibody raised against the GAP catalytic peptide
      previously purified by Makler et al. [Makler, Cukierman, Rotman, Admon and Cassel
      (1995) J. Biol. Chem. 270, 5232-5237], and here is referred to as GAP1. The other
      GAP (GAP2) did not react with the antibody. These GAPs differed in phospholipid
      dependencies. GAP1 was activated 3-7-fold by the acid phospholipids
      phosphatidylinositol 4, 5-bisphosphate (PIP2), phosphatidic acid (PA) and
      phosphatidylserine (PS). In contrast, GAP2 was stimulated 20-40-fold by PIP2. PA
      and PS had no effect by themselves but PA increased GAP2 activity in the presence
      of PIP2. The GAPs were otherwise similar in activity. In the presence of
      phosphoinositides, the Km of GAP1 for ARF1-GTP was estimated to be 8.1+/-1.6
      microM and the dissociation constant for ARF1-guanosine 5',3-O-(thio)triphosphate
      (GTP[S]) was 7.4+/-2.2 microM. GAP2 was similar with a Km for ARF1-GTP of 5.4+/
      1.2 microM and a dissociation constant for ARF1-GTP[S] of 4.8+/-0.3 microM.
      Similarly, no differences were found in substrate preferences. Both GAP1 and GAP2
      used ARF1 and ARF5 as substrates but not ARF6 or ARF-like protein-2. The
      potential role of multiple ARF GAPs in the independent regulation of ARF at
      specific steps in membrane traffic is discussed.

PMID- 9182699
TI  - Expression of an exogenous isopentenyl diphosphate isomerase gene enhances
      isoprenoid biosynthesis in Escherichia coli.
AB  - Escherichia coli expressing the Erwinia carotenoid biosynthesis genes, crtE,
      crtB, crtI and crtY, form yellow-coloured colonies due to the presence of beta
      carotene. This host was used as a visible marker for evaluating regulatory
      systems operating in isoprenoid biosynthesis of E. coli. cDNAs enhancing
      carotenoid levels were isolated from the yeast Phaffia rhodozyma and the green
      alga Haematococcus pluvialis. Nucleotide sequence analysis indicated that they
      coded for proteins similar to isopentenyl diphosphate (IPP) isomerase of the
      yeast Saccharomyces cerevisiae. Determination of enzymic activity confirmed the
      identity of the gene products as IPP isomerases. The corresponding gene was
      isolated from the genomic library of S. cerevisiae based on its nucleotide
      sequence, and was confirmed to have the same effect as the above two IPP
      isomerase genes when introduced into the E. coli transformant accumulating beta
      carotene. In the three E. coli strains carrying the individual exogenous IPP
      isomerase genes, the increases in carotenoid levels are comparable to the
      increases in IPP isomerase enzyme activity with reference to control strains
      possessing the endogenous gene alone. These results imply that IPP isomerase
      forms an influential step in isoprenoid biosynthesis of the prokaryote E. coli,
      with potential for the efficient production of industrially useful isoprenoids by
      metabolic engineering.

PMID- 9182700
TI  - Latent transforming growth factor-beta complex in Chinese hamster ovary cells
      contains the multifunctional cysteine-rich fibroblast growth factor receptor,
      also termed E-selectin-ligand or MG-160.
AB  - Transforming growth factor-beta (TGF-beta) is secreted as latent high molecular
      mass complexes from producer cells. The N-terminal precursor remnant, also called
      latency-associated peptide (LAP), forms a non-covalently linked complex with TGF
      beta and confers the latency to TGF-beta. In human platelets and certain other
      cell types, latent TGF-beta binding protein-1 (LTBP-1) is disulphide-linked to
      LAP, and forms complexes of more than 230 kDa. In addition, LTBP-2 and -3, which
      are structurally similar to LTBP-1, can be part of latent TGF-beta complexes. In
      Chinese hamster ovary (CHO) cells transfected with the TGF-beta1 cDNA, a major
      part of the latent TGF-beta secreted into the medium is a 100-kDa small latent
      complex containing TGF-beta and LAP. In addition, we found two other forms of
      latent TGF-beta complexes, i.e. a 220-kDa complex containing LTBP-1, and a 220
      kDa complex containing a 140-kDa protein. Purification of the 140-kDa component,
      termed latent TGF-beta complexed protein-1 (LTCP-1), followed by amino acid
      sequencing and cDNA cloning from a CHO cell cDNA library, revealed that it is a
      hamster counterpart of a previously identified, multifunctional protein known as
      chicken cysteine-rich fibroblast growth factor (FGF) receptor, mouse E-selectin
      ligand and rat MG-160 (a 160-kDa membrane sialoglycoprotein of the Golgi
      apparatus). Immunoprecipitation of LTCP-1 and TGF-beta1 from CHO cells stably
      transfected with TGF-beta1 precursor cDNA revealed that the expressed protein
      forms a complex with LAP, and that a major part of the complex is secreted.
      Northern blot analysis showed that mRNA for LTCP-1 was expressed in large amounts
      in testis, ovary and placenta, but less abundantly in other tissues. These
      results suggest that TGF-beta, produced in certain cell types, may form a complex
      with LTCP-1, which may have different properties compared with other latent TGF
      beta complexes. It remains to be investigated whether the complex formation
      between LTCP-1 and TGF-beta1 also occurs in other cells, whether the association
      between them occurs in the Golgi complex, and whether it affects the interaction
      of LTCP-1 with FGF or E-selectin.

PMID- 9182702
TI  - Cloning of the monocarboxylate transporter isoform MCT2 from rat testis provides
      evidence that expression in tissues is species-specific and may involve post
      transcriptional regulation.
AB  - The cDNA for the monocarboxylate transporter MCT2 from rat testis has been cloned
      and sequenced. The derived protein sequence shows 82% identity with that from
      hamster. Rat MCT2 has a relative insertion of five amino acids in the N-terminal
      sequence preceding the first predicted transmembrane segment. MCT2 appears to be
      less highly conserved between species than MCT1. Using Northern blotting of RNA
      from rat and mouse tissues, MCT2 message was demonstrated to be abundant in the
      testis where a smaller, less abundant MCT2 transcript was also present. Low
      levels of a slightly different-sized transcript were found in rat and mouse
      liver, and mouse kidney. In hamster, only one-size transcript was detected at
      relatively high abundance in all the tissues examined. Antibodies were raised
      against a peptide derived from the extreme C-terminus of rat MCT2, and Western
      blotting with these detected MCT2 in membrane fractions prepared from rat testis,
      liver and brain but not those from heart or skeletal muscle. In hamster, MCT2 was
      detected in liver, heart and testis but not in brain [Garcia, Brown, Pathak, and
      Goldstein (1995) J. Biol. Chem. 270, 1843-1849]. For both rat MCT1 and MCT2 there
      were marked differences between the relative abundance of their respective
      messages and the amount of protein in membrane fractions from different tissues.
      This suggests that expression of both of these transporters in different tissues
      may be species-specific and regulated post-transcriptionally. The different-sized
      MCT2 transcripts may arise from alternative splicing. Starvation of rats for up
      to 48 h did not lead to any change in MCT1 or MCT2 expression in the liver, as
      determined by either Northern or Western blotting.

PMID- 9182701
TI  - Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves
      phosphatidylserine and direct serine decarboxylation.
AB  - Erythrocytes infected with Plasmodium falciparum or Plasmodium knowlesi
      efficiently incorporated radioactive serine into phosphatidylserine (PtdSer),
      phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho). Serine was
      also metabolized into ethanolamine (Etn) and phosphorylethanolamine (P-Etn) via
      direct serine decarboxylation; this is a major phenomenon since together these
      metabolites represent 60% of total radioactive water-soluble metabolites. They
      were identified by reverse-phase HPLC and two TLC-type analyses and confirmed by
      alkaline phosphatase treatment, which depleted the radioactive P-Etn peak
      completely with a concomitant increase in that of Etn. In the presence of 5
      microM labelled serine, radioactivity appeared in Etn and P-Etn after a 25 min
      lag period, and isotopic equilibrium was reached at 40 and 95 min respectively.
      There was a similar lag period for PtdEtn formation, which accumulated steadily
      for at least 180 min. Incorporation of serine into phospholipids and water
      soluble metabolites increased in the presence of up to 500 microM external
      serine. An apparent plateau was then reached for all metabolites except
      intracellular serine and Etn. Exogenous Etn (at 20 microM) induced a concomitant
      dramatic decrease in serine incorporation into P-Etn and all phospholipids, but
      not into Etn. Increasing exogenous serine to 100 microM decreased the
      incorporation of radioactive Etn into PtdEtn by only 30%, and the PtdCho level
      was not affected. 2-Hydroxyethylhydrazine significantly decreased serine
      incorporation into P-Etn and PtdEtn, whereas Etn was accumulated. No concomitant
      inhibition of PtdSer or PtdCho labelling from serine occurred, even when PtdEtn
      formation was decreased by 95%. This indicates that the PtdEtn pool derived from
      direct serine decarboxylation differed from that derived from PtdSer
      decarboxylation, and the latter appeared to be preferentially used for PtdCho
      biosynthesis. Hydroxylamine also inhibited phosphorylation of serine-derived Etn
      but not that of exogenous Etn. The rate of PtdSer synthesis from 10 microM L
      serine was 3.1+/-0.5 and 2.95+/-1.3 nmol/5 h per 10(10) infected cells, whereas L
      serine decarboxylation accounted for 7.1+/-1.5 and 9.9+/-3 nmol/5 h per 10(10)
      infected cells for P. falciparum and P. knowlesi respectively (means+/-S.E.M.).
      The serine decarboxylating reaction was not detected in other higher eukaryotic
      cells such as mouse fibroblasts and human lymphocytes. Finally, these results
      also indicate compartmentalization of phospholipid metabolism in Plasmodium
      infected erythrocytes.

PMID- 9182703
TI  - Heterologous expression of rab4 reduces glucose transport and GLUT4 abundance at
      the cell surface in oocytes.
AB  - To evaluate the role of the small rab GTP-binding proteins in glucose transporter
      trafficking, we have heterologously co-expressed rab4 or rab5 and GLUT4 or GLUT1
      glucose transporters in Xenopus oocytes. Co-injection of rab4 and GLUT4 cRNAs
      resulted in a dose-dependent decrease in glucose transport; this effect was
      specific for rab4, since co-injection of an inactive rab4 mutant or rab5 cRNA did
      not have any effect on glucose transport. The effect of rab4 was selective for
      GLUT4, since no effect was detected in GLUT1-expressing oocytes. The inhibitory
      effect of rab4 on GLUT4-induced glucose transport was not the result of a change
      in overall cellular levels of GLUT4 glucose transporters. However, rab4
      expression caused a marked decrease in the abundance of GLUT4 transporters
      present at the cell surface. Finally, rab4 and inhibitors of PtdIns 3-kinase
      showed additive effects in decreasing glucose transport in GLUT4-expressing
      oocytes. We conclude that rab4 plays an important role in the regulation of the
      intracellular GLUT4 trafficking pathway, by contributing to the intracellular
      retention of GLUT4 through a PtdIns 3-kinase-independent mechanism.

PMID- 9182704
TI  - Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein: implications
      for a role in axonal guidance.
AB  - Neurotrophin-6 (NT-6) was identified in the teleost fish Xiphophorus as a new
      member of the neurotrophin gene family. NT-6 binds specifically the
      glycosaminoglycan heparin. In this study NT-6 was expressed in a stably
      transfected mammalian cell line, and in insect cells via a recombinant
      baculovirus. It was purified to homogeneity and characterized by MS and N
      terminal sequencing. NT-6 from both expression systems was proteolytically
      processed at one of two protease cleavage motifs and was found to be
      glycosylated. It supported the survival of embryonic chick sensory neurons; half
      maximal survival was observed at 100 ng/ml. Furthermore, NT-6 elicited neurite
      outgrowth in explanted embryonic dorsal root ganglia. Addition of heparin into
      the medium did not potentiate the activity of NT-6 in survival assays. However,
      when a sensory ganglion explant was cultured in a collagen gel matrix assay
      adjacent to a heparin bead coated with NT-6, neurite outgrowth directed towards
      the bead was observed. This indicated that NT-6 was slowly released from the
      heparin bead generating a concentration gradient of NT-6 instrumental for axonal
      guidance in vitro. Thus the interaction of NT-6 with heparin might not be
      required for the activation of the cellular receptor for NT-6 on responsive cells
      but rather may serve to control, in vivo, the distribution of NT-6.

PMID- 9182705
TI  - Tight links between adenine and guanine nucleotide pools in mouse pancreatic
      islets: a study with mycophenolic acid.
AB  - Glucose metabolism in pancreatic B-cells leads to an increase in the ATP/ADP
      ratio that might participate in the regulation of insulin secretion. Good
      correlations have also been observed between guanine nucleotide levels in
      isolated pancreatic islets and insulin secretion. To assess whether guanine
      nucleotides have a specific role in stimulus-secretion coupling, their
      concentration should be modified selectively. This was attempted by culturing
      mouse islets overnight in the presence of mycophenolic acid (MPA), an inhibitor
      of GMP synthesis at the level of IMP dehydrogenase. The drug (25-50 microg/ml)
      did not affect the insulin content but decreased the GTP content of the islets
      and inhibited insulin secretion during subsequent incubation in the presence of
      15 mM glucose. However, MPA also decreased the ATP/ADP ratio in the islets. The
      addition of guanine to the culture medium (to stimulate the salvage pathway of
      GTP synthesis) restored normal GTP levels, corrected the ATP/ADP ratio and partly
      prevented the inhibition of insulin release. In contrast, attempts to stimulate
      ATP synthesis specifically (by provision of adenine or adenosine) failed to
      reverse any of the effects of MPA. It is concluded that guanine and adenine
      nucleotide pools are tightly linked and cannot be specifically affected by MPA in
      pancreatic islet cells, probably because of the activity of nucleoside
      diphosphate kinase and because of the role of GTP in several reactions leading to
      adenine nucleotide generation. Contrary to previous claims, MPA is not an
      adequate tool for evaluating a specific role of guanine nucleotides in the
      control of insulin secretion.

PMID- 9182706
TI  - Nitric oxide degradation of heparin and heparan sulphate.
AB  - NO is a bioactive free radical produced by NO synthase in various tissues
      including vascular endothelium. One of the degradation products of NO is HNO2, an
      agent known to degrade heparin and heparan sulphate. This report documents
      degradation of heparin by cultured endothelial-cell-derived as well as exogenous
      NO. An exogenous narrow molecular-mass preparation of heparin was recovered from
      the medium of cultured endothelial cells using strong-anion exchange. In
      addition, another narrow molecular-mass preparation of heparin was gassed with
      exogenous NO under argon. Degradation was evaluated by gel-filtration
      chromatography. Since HNO2 degrades heparin under acidic conditions, the reaction
      with NO gas was studied under various pH conditions. The results show that the
      degradation of exogenous heparin by endothelial cells is inhibited by NO synthase
      inhibitors. Exogenous NO gas at concentrations as low as 400 p.p.m. degrades
      heparin and heparan sulphate. Exogenous NO degrades heparin at neutral as well as
      acidic pH. Endothelial-cell-derived NO, as well as exogenous NO gas, did not
      degrade hyaluronan, an unrelated glycosaminoglycan that resists HNO2 degradation.
      Peroxynitrite, a metabolic product of the reaction of NO with superoxide, is an
      agent that degrades hyaluronan; however, peroxynitrite did not degrade heparin.
      Thus endothelial-cell-derived NO is capable of degrading heparin and heparan
      sulphate via HNO2 rather than peroxynitrite. These observations may be relevant
      to various pathophysiological processes in which extracellular matrix is
      degraded, such as bone development, apoptosis, tissue damage from inflammatory
      responses and possible release of growth factors and cytokines.

PMID- 9182707
TI  - Sphingosine 1-phosphate stimulates rho-mediated tyrosine phosphorylation of focal
      adhesion kinase and paxillin in Swiss 3T3 fibroblasts.
AB  - Sphingosine 1-phosphate (SPP), a sphingolipid second messenger implicated in the
      mitogenic action of platelet-derived growth factor [Olivera, A. and Spiegel, S.
      (1993) Nature (London) 365, 557-560], induced rapid reorganization of the actin
      cytoskeleton resulting in stress-fibre formation. SPP also induced transient
      tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), a cytosolic
      tyrosine kinase that localizes in focal adhesions, and of the cytoskeleton
      associated protein paxillin. Exoenzyme C3 transferase, which ADP-ribosylates Rho
      (a Ras-related small GTP binding protein) on asparagine-41 and renders it
      biologically inactive, inhibited both stress-fibre formation and protein tyrosine
      phosphorylation induced by SPP. Thus Rho may be an upstream regulator of both
      stress-fibre formation and tyrosine phosphorylation of p125(FAK) and paxillin.
      Pretreatment with PMA, an activator of protein kinase C (PKC), inhibited the
      stimulation of stress-fibre formation induced by 1-oleoyl-lysophosphatidic acid
      (LPA) but not that by SPP. Similarly, PMA also decreased LPA-induced tyrosine
      phosphorylation of p125(FAK) and paxillin without abrogating the response to SPP.
      Thus PKC is involved in LPA- but not SPP-dependent signalling. The polyanionic
      drug suramin, a broad-specificity inhibitor of ligand-receptor interactions, did
      not inhibit either the mitogenic effect of SPP or its stimulation of tyrosine
      phosphorylation of p125(FAK). However, suramin markedly inhibited these responses
      induced by LPA. These results suggest that in contrast with LPA, SPP may be
      acting intracellularly in Swiss 3T3 fibroblasts to stimulate tyrosine
      phosphorylation of p125(FAK) and paxillin and cell growth.

PMID- 9182709
TI  - Reactions of the oxidized organic cofactor in copper-depleted bovine serum amine
      oxidase.
AB  - A novel copper-depleted bovine serum amine oxidase (BSAO), in which about half
      the molecules contained the organic cofactor in the oxidized form, was prepared
      by adding a reductant in anaerobic conditions to the cyanide-reacted protein. The
      CuI-semiquinone formed in these conditions reoxidizes after the removal of
      copper. The inactive derivative was reduced by benzylamine at approx. 1/1000 the
      rate of BSAO. The pseudo-first-order reaction was preceded by the formation of a
      protein-benzylamine complex with dissociation constant, Kd, of 4.9+/-0.5 mM,
      similar to the Km of BSAO (2.2 mM). Also the reactions with phenylhydrazine and
      benzohydrazide were considerably slower than in holo-BSAO, whereas the reactions
      with p-pyridine-2-ylphenylacetohydrazide, containing a longer aromatic tail, and
      semicarbazide, lacking an aromatic moiety, were less severely affected. Removal
      of copper had no effect on the optical spectra of BSAO and of most adducts,
      containing the cofactor in quinol form, showing that copper is bound to neither
      the oxidized nor the reduced cofactor. Benzylhydrazine did not produce optical
      effects but was tightly bound, as inferred from its inhibitory effect on reaction
      with other molecules. Substrate and inhibitors might bind a hydrophobic pocket at
      some distance from the quinone, probably near the protein surface, with their
      affinity depending on the hydrophobic character and pKa. The binding, which is
      not greatly influenced by copper removal, probably induces a copper-dependent
      change of conformation, 'opening' a pathway to the active site buried in the
      protein interior.

PMID- 9182708
TI  - Lipid kinase and protein kinase activities of G-protein-coupled phosphoinositide
      3-kinase gamma: structure-activity analysis and interactions with wortmannin.
AB  - Signalling via seven transmembrane helix receptors can lead to a massive increase
      in cellular PtdIns(3,4,5)P3, which is critical for the induction of various cell
      responses and is likely to be produced by a trimeric G-protein-sensitive
      phosphoinositide 3-kinase (PI3Kgamma). We show here that PI3Kgamma is a
      bifunctional lipid kinase and protein kinase, and that both activities are
      inhibited by wortmannin at concentrations equal to those affecting the
      p85/p110alpha heterodimeric PI3K (IC50 approx. 2 nM). The binding of wortmannin
      to PI3Kgamma, as detected by anti-wortmannin antisera, closely followed the
      inhibition of the kinase activities. Truncation of more than the 98 N-terminal
      amino acid residues from PI3Kgamma produced proteins that were inactive in
      wortmannin binding and kinase assays. This suggests that regions apart from the
      core catalytic domain are important in catalysis and inhibitor interaction. The
      covalent reaction of wortmannin with PI3Kgamma was prevented by preincubation
      with phosphoinositides, ATP and its analogues adenine and 5'-(4
      fluorosulphonylbenzoyl)adenine. Proteolytic analysis of wortmannin-prelabelled
      PI3Kgamma revealed candidate wortmannin-binding peptides around Lys-799.
      Replacement of Lys-799 by Arg through site-directed mutagenesis aborted the
      covalent reaction with wortmannin and the lipid kinase and protein kinase
      activities completely. The above illustrates that Lys-799 is crucial to the
      phosphate transfer reaction and wortmannin reactivity. Parallel inhibition of the
      PI3Kgamma-associated protein kinase and lipid kinase by wortmannin and by the Lys
      799-->Arg mutation reveals that both activities are inherent in the PI3Kgamma
      polypeptide.

PMID- 9182710
TI  - ADP-glucose drives starch synthesis in isolated maize endosperm amyloplasts:
      characterization of starch synthesis and transport properties across the
      amyloplast envelope.
AB  - We recently developed a method of purifying amyloplasts from developing maize
      (Zea mays L.) endosperm tissue [Neuhaus, Thom, Batz and Scheibe (1993) Biochem.
      J. 296, 395-401]. In the present paper we analyse how glucose 6-phosphate (Glc6P)
      and other phosphorylated compounds enter the plastid compartment. Using a
      proteoliposome system in which the plastid envelope membrane proteins are
      functionally reconstituted, we demonstrate that this type of plastid is able to
      transport [14C]Glc6P or [32P]Pi in counter exchange with Pi, Glc6P,
      dihydroxyacetone phosphate and phosphoenolpyruvate. Glucose 1-phosphate, fructose
      6-phosphate and ribose 5-phosphate do not act as substrates for counter exchange.
      Besides hexose phosphates, ADP-glucose (ADPGlc) also acts as a substrate for
      starch synthesis in isolated maize endosperm amyloplasts. This process exhibits
      saturation kinetics with increasing concentrations of exogenously supplied
      [14C]ADPGlc, reaching a maximum at 2mM. Ultrasonication of isolated amyloplasts
      greatly reduces the rate of ADPGlc-dependent starch synthesis, indicating that
      the process is dependent on the intactness of the organelles. The plastid ATP/ADP
      transporter is not responsible for ADPGlc uptake. Data are presented that
      indicate that ADPGlc is transported by another translocator in counter exchange
      with AMP. To analyse the physiology of starch synthesis in more detail, we
      examined how Glc6P- and ADPGlc-dependent starch synthesis in isolated maize
      endosperm amyloplasts interact. Glc6P-dependent starch synthesis is not inhibited
      by increasing concentrations of ADPGlc. In contrast, the rate of ADPGlc-dependent
      starch synthesis is reduced by increasing concentrations of ATP necessary for
      Glc6P-dependent starch synthesis. The possible modes of inhibition of ADPGlc
      dependent starch synthesis by ATP are discussed with respect to the stromal
      generation of AMP required for ADPGlc uptake.

PMID- 9182711
TI  - pH-dependence for binding a single nitrite ion to each type-2 copper centre in
      the copper-containing nitrite reductase of Alcaligenes xylosoxidans.
AB  - The first quantitative characterization of the interaction of NO2(-) with the Cu
      containing dissimilatory nitrite reductase (NiR) of Alcaligenes xylosoxidans
      using steady-state kinetics, equilibrium gel filtration and EPR spectroscopy is
      described. Each molecule of this protein consists of three equivalent subunits,
      each containing a type-1 Cu atom and also a type-2 Cu atom at each subunit
      interface. Enzyme activity increased in a biphasic manner with decreasing pH,
      having an optimum at pH 5.2 and a plateau between pH 6.1 and 5.8. Equilibrium gel
      filtration showed that binding of NO2(-) to the oxidized NiR was also pH
      dependent. At pH 7.5, no binding was detectable, but binding was detectable at
      lower pH values. At pH 5.2, the concentration-dependence for binding of NO2(-) to
      the enzyme showed that approx. 4.1 NO2(-) ions bound per trimeric NiR molecule.
      Unexpectedly, NiR deficient in type-2 Cu centres bound 1.3 NO2(-) ions per
      trimer. When corrected for this binding, a value of 3 NO2(-) ions bound per
      trimer of NiR, equivalent to the type-2 Cu content. The NO2(-)-induced changes in
      the EPR parameters of the type-2 Cu centre of the oxidized enzyme showed a
      similar pH-dependence to that of the activity. Binding constants for NO2(-) at a
      single type of site, after allowing for the non-specifically bound NO2(-), were
      350+/-35 microM (mean+/-S.E.M.) at pH 7.5 and <30 microM at pH 5.2. The apparent
      Km for NO2(-) with saturating concentrations of dithionite as reductant was 35
      microM at pH 7.5, which is 10-fold tighter than for the oxidized enzyme, and is
      compatible with an ordered mechanism in which the enzyme is reduced before NO2(-)
      binds.

PMID- 9182712
TI  - Structural features that make oligopeptides susceptible substrates for hydrolysis
      by recombinant thimet oligopeptidase.
AB  - A systematic analysis of the peptide sequences and lengths of several homologues
      of bioactive peptides and of a number of quenched-fluorescence (qf) opioid- and
      bradykinin-related peptides was performed to determine the main features leading
      the oligopeptides to hydrolysis by the recombinant rat testis thimet
      oligopeptidase (EC 3.4.24.15). The results indicate that a minimum substrate
      length of six amino acids is required and that among the oligopeptides six to
      thirteen amino acid residues long, their susceptibility as substrates is highly
      variable. Thimet oligopeptidase was able to hydrolyse, with similar catalytic
      efficiency, peptide bonds having hydrophobic or hydrophilic amino acids as well
      as proline in the P1 position of peptides, ranging from a minimum of six to a
      maximum of approximately thirteen amino acid residues. An intriguing observation
      was the shift of the cleavage site, at a Leu-Arg bond in qf dynorphin-(2-8) [qf
      Dyn2-8; Abz-GGFLRRV-EDDnp, where Abz stands for o-aminobenzoyl and EDDnp for N
      (2,4-dinitrophenyl)ethylenediamine], to Arg-Arg in qf-Dyn2-8Q, in which Gln was
      substituted for Val at its C-terminus. Similarly, a cleavage site displacement
      was also observed with the hydrolysis of the internally quenched-fluorescence
      bradykinin analogues containing Gln at the C-terminal position, namely Abz
      RPPGFSPFR-EDDnp and Abz-GFSPFR-EDDnp are cleaved at the Phe-Ser bond, but Abz
      RPPGFSPFRQ-EDDnp and Abz-GFSPFRQ-EDDnp are cleaved at the Pro-Phe bond.

PMID- 9182713
TI  - Isolation of peptides from phage-displayed random peptide libraries that interact
      with the talin-binding domain of vinculin.
AB  - Peptides isolated from combinatorial libraries typically interact with, and thus
      help to characterize, biologically relevant binding domains of target proteins.
      To characterize the binding domains of the focal adhesion protein vinculin,
      vinculin-binding peptides were isolated from two phage-displayed random peptide
      libraries. Altogether, five non-similar vinculin-binding peptides were
      identified. Despite the lack of obvious sequence similarity between the peptides,
      binding and competition studies indicated that all five interact with the talin
      binding domain of vinculin and do not disrupt the binding of alpha-actinin or
      paxillin to vinculin. The identified peptides and talin bind to vinculin in a
      comparable manner; both bind to immobilized vinculin, but neither binds to
      soluble vinculin unless the C-terminus of vinculin has been deleted. An analysis
      of amino acid variants of one of the peptides has revealed three non-contiguous
      motifs that also occur in the region of talin previously demonstrated to bind
      vinculin. Amino acid substitutions within a 127-residue segment of talin capable
      of binding vinculin confirmed the importance of two of the motifs and suggest
      that residues critical for binding are within a 16-residue region. This study
      demonstrates that the vinculin-binding peptides interact with vinculin in a
      biologically relevant manner and represent an excellent tool for further study of
      the biochemistry of vinculin.

PMID- 9182714
TI  - Triacsin C blocks de novo synthesis of glycerolipids and cholesterol esters but
      not recycling of fatty acid into phospholipid: evidence for functionally separate
      pools of acyl-CoA.
AB  - The trafficking of acyl-CoAs within cells is poorly understood. In order to
      determine whether newly synthesized acyl-CoAs are equally available for the
      synthesis of all glycerolipids and cholesterol esters, we incubated human
      fibroblasts with [14C]oleate, [3H]arachidonate or [3H]glycerol in the presence or
      absence of triacsin C, a fungal metabolite that is a competitive inhibitor of
      acyl-CoA synthetase. Triacsin C inhibited de novo synthesis from glycerol of
      triacylglycerol, diacylglycerol and cholesterol esters by more than 93%, and the
      synthesis of phospholipid by 83%. However, the incorporation of oleate or
      arachidonate into phospholipids appeared to be relatively unimpaired when
      triacsin was present. Diacylglycerol acyltransferase and lysophosphatidylcholine
      acyltransferase had similar dependences on palmitoyl-CoA in both liver and
      fibroblasts; thus it did not appear that acyl-CoAs, when present at low
      concentrations, would be preferentially used to acylate lysophospholipids. We
      interpret these data to mean that, when fatty acid is not limiting, triacsin
      blocks the acylation of glycerol 3-phosphate and diacylglycerol, but not the
      reacylation of lysophospholipids. Two explanations are possible: (1) different
      acyl-CoA synthetases exist that vary in their sensitivity to triacsin; (2) an
      independent mechanism channels acyl-CoA towards phospholipid synthesis when
      little acyl-CoA is available. In either case, the acyl-CoAs available to acylate
      cholesterol, glycerol 3-phosphate, lysophosphatidic acid and diacylglycerol and
      those acyl-CoAs that are used by lysophospholipid acyltransferases and by
      ceramide N-acyltransferase must reside in two non-mixing acyl-CoA pools or, when
      acyl-CoAs are limiting, they must be selectively channelled towards specific
      acyltransferase reactions.

PMID- 9182716
TI  - Effects of epidermal growth factor and insulin on the activity of N
      acetylglucosaminyltransferase V.
AB  - When quiescent rat hepatocellular carcinoma 7919 cells were treated with
      epidermal growth factor (EGF) or insulin (stimulators of receptor tyrosine kinase
      activity), the activity of N-acetylglucosaminyltransferase V was increased. The
      effect of EGF reached a maximum after 10 min and remained high for 30 min, while
      the effect of insulin reached a maximum after 5 min and decreased after 15 min.
      Preincubation of the cells with 1-O-octadecyl-2-O-methylglycerophosphocholine
      (Et18-OH3), which blocked the activation of mitogen-activated protein kinase by
      EGF, also blocked the activation of N-acetylglucosamyltransferase V by this
      hormone, whereas the activation of N-acetylglucosamyltransferase V by insulin
      could not be blocked by Et18-OH3. Our results suggest that N
      acetylglucosamyltransferase V may be regulated by different receptor protein
      tyrosine kinase pathways.

PMID- 9182715
TI  - Expression of the surface antigen 4F2hc affects system-L-like neutral-amino-acid
      transport activity in mammalian cells.
AB  - Mammalian cells possess a variety of amino acid-transport systems with
      overlapping substrate specificity. System L is one of the major amino acid
      transport systems of non-epithelial cells. By expression cloning we have recently
      demonstrated that the surface antigen 4F2hc (CD98) is a necessary component for
      expression of system-L-like amino acid-transport activity in C6-BU-1 rat glioma
      cells [Broer, Broer and Hamprecht (1995) Biochem. J. 312, 863-870]. 4F2hc mRNA
      was detected in CHO cells, COS cells, activated lymphocytes isolated from mouse
      spleen and primary cultures of astrocytes. In all these cell types, Na+
      independent isoleucine transport was mediated by system L. No contribution of
      system y+L to isoleucine or arginine transport was detected in C6-BU-1 cells. In
      lymphocytes, both system-L-like amino acid-transport activity and 4F2hc mRNA
      levels increased after treatment with phorbol ester plus ionomycin. Antisense
      oligonucleotides caused modest inhibition of Na+-independent isoleucine transport
      in C6-BU-1 cells and primary cultures of astroglial cells, whereas arginine
      transport was unaffected. Overexpression of 4F2hc cDNA in CHO cells resulted in
      an increase in Na+-independent isoleucine transport.

PMID- 9182717
TI  - Differential functional significance of AP-1 binding sites in the promoter of the
      gene encoding mouse tissue inhibitor of metalloproteinases-3.
AB  - Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular-matrix
      associated protein that suppresses tumorigenicity or invasion in several model
      systems. We have identified, by in vitro footprinting, six AP-1 (activator
      protein-1) or AP-1-like binding sites in the mouse TIMP-3 promoter that bind
      purified c-Jun homodimers. Electrophoretic mobility shift assays revealed that
      the non-consensus fifth AP-1 binding site (AP-720; nt -720 to -714) had the
      strongest binding activity for recombinant c-Jun protein, and that the fourth
      binding site (AP-763; nt -763 to -754) and AP-720 showed strong binding activity
      for cellular nuclear proteins. Antibody supershift and blocking experiments
      suggest that AP-720, but not AP-763, binds authentic AP-1 components. Transient
      transfection reporter assays of deletion constructs showed that the region
      spanning AP-720 has the highest transcriptional activity, and that sequences 5'
      to this region (nt -2846 to -747) may contain negative regulatory elements. The
      deletion construct containing about 500 nt 5' to the transcriptional start, but
      no AP-1 sites, showed lower but significant activity, suggesting both AP-1
      dependent and -independent regulation of the mouse TIMP-3 promoter. Mutational
      inactivation of AP-720 abolished the activity increment that distinguished the
      reporter construct containing both AP-720 and sixth AP-1 binding site (AP-617; nt
      -617 to -611) from that containing only AP-617. In summary, we report here that
      both AP-1 and non-AP-1 elements contribute to activity, with the non-consensus AP
      1 site at -720 showing the greatest functional significance among the AP-1 sites.

PMID- 9182719
TI  - N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of
      proteins by methylglyoxal, increases with age in human lens proteins.
AB  - Advanced glycation end-products and glycoxidation products, such as Nepsilon
      (carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue
      proteins with age and are implicated in the aging of tissue proteins and in the
      development of pathology in diabetes, atherosclerosis and other diseases. In this
      paper we describe a new advanced glycation end-product, Nepsilon
      (carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal
      with lysine residues in model compounds and in the proteins RNase and collagen.
      CEL was also detected in human lens proteins at a concentration similar to that
      of CML, and increased with age in parallel with the concentration of CML.
      Although CEL was formed in highest yields during the reaction of methylglyoxal
      and triose phosphates with lysine and protein, it was also formed in reactions of
      pentoses, ascorbate and other sugars with lysine and RNase. We propose that
      levels of CML and CEL and their ratio to one another in tissue proteins and in
      urine will provide an index of glyoxal and methylglyoxal concentrations in
      tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in
      disease, and sources of advanced glycation end-products in tissue proteins in
      aging and disease.

PMID- 9182718
TI  - Purification of a dichlorophenol-indophenol oxidoreductase from rat and bovine
      synaptic membranes: tight complex association of a glyceraldehyde-3-phosphate
      dehydrogenase isoform, TOAD64, enolase-gamma and aldolase C.
AB  - NADH-dichlorophenol-indophenol oxidoreductases (PMOs) were purified from synaptic
      plasma membranes or synaptic vesicles (small recycling vesicles) from both bovine
      and rat brains and from a neuroblastoma cell line, NB41A3. Several isoforms could
      be identified in purified plasma membranes and vesicles. Purification of the
      enzyme activity involved protein extraction with detergents, (NH4)2SO4
      precipitation, chromatography under stringent conditions and native PAGE. PMO
      activity could be attributed to a very tight complex of several proteins that
      could not be separated except by SDS/PAGE. SDS/PAGE resolved the purified complex
      into at least five proteins, which could be micro-sequenced and identified
      unambiguously as hsc70, TOAD64 and glyceraldehyde-3-phosphate dehydrogenase
      tightly associated with the brain-specific proteins aldolase C and enolase-gamma.
      Enzyme activity could be purified from both synaptic plasma membranes and
      recycling vesicles, yields being much greater from the latter source. Highly
      purified plasma membranes (prepared from a neuroblastoma cell line NB41A3 by
      iminobiotinylation of intact cells and affinity purification with avidin and anti
      avidin antibodies under very stringent conditions) also displayed PMO activity
      tightly associated with TOAD64. The association of PMO in a tight complex was
      confirmed by its immunoprecipitation from cellular and membrane extracts of
      NB41A3 using antibodies directed against any component protein of the complex
      followed by immunodetection with antibodies directed against the other members.
      Antibodies also inhibited the enzyme activity synergistically. In addition,
      induction of the different components of the complex during dichlorophenol
      indophenol stress was demonstrated by the S1 RNase-protection assay in
      synchronized NB41A3 cells. The role of the complex in membrane fusion and
      cellular response to extracellular oxidative stress during growth and development
      is discussed.

PMID- 9182720
TI  - Influence of the conserved disulphide bond, exposed to the putative binding
      pocket, on the structure and function of the immunoglobulin-like molecular
      chaperone Caf1M of Yersinia pestis.
AB  - The Yersinia pestis protein Caf1M is a typical representative of a subfamily of
      periplasmic molecular chaperones with characteristic structural and functional
      features, one of which is the location of two conserved cysteine residues close
      to the putative binding pocket. We show that these residues form a disulphide
      bond, the reduction and alkylation of which significantly increases the
      dissociation constant of the Caf1M-Caf1 (where Caf 1 is a polypeptide subunit of
      the capsule) complex [from a Kd of (4.77+/-0.50)x10(-9) M for the intact protein
      to one of (3.68+/-0.68)x10(-8) M for the modified protein]. The importance of the
      disulphide bond for the formation of functional Caf1M in vivo was demonstrated
      using an Escherichia coli dsbA mutant carrying the Y. pestis f1 operon. In
      accordance with the CD and fluorescence measurements, the disulphide bond is not
      important for maintenance of the overall structure of the Caf1M molecule, but
      would appear to affect the fine structural properties of the subunit binding
      site. A three-dimensional model of the Caf1M-Caf1 complex was designed based on
      the published crystal structure of PapD (a chaperone required for Pap pili
      assembly) complexed with a peptide corresponding to the C-terminus of the papG
      subunit. In the model the disulphide bond is in close proximity to the invariant
      Caf1M Arg-23 and Lys-142 residues that are assumed to anchor the C-terminal group
      of the subunit. The importance of this characteristic disulphide bond for the
      orchestration of the binding site and subunit binding, as well as for the folding
      of the protein in vivo, is likely to be a common feature of this subfamily of
      Caf1M-like chaperones. A possible model for the role of the disulphide bond in
      Caf1 assembly is discussed.

PMID- 9182721
TI  - Membrane association, localization and topology of rat inositol 1,4,5
      trisphosphate 3-kinase B: implications for membrane traffic and Ca2+
      homoeostasis.
AB  - We previously reported the isolation of a rat cDNA clone encoding a protein with
      significant sequence homology to the B isoform of human myo-inositol 1,4,5
      trisphosphate 3-kinase (IP3 3-kinase B); this protein was thus designated rat IP3
      3-kinase B [Thomas, Brake, Luzio, Stanley and Banting (1994) Biochim. Biophys.
      Acta 1220, 219-222]. However, no IP3 kinase isoform had been shown to generate
      the physiologically important isoform of inositol tetrakisphosphate, i.e.
      inositol 1,3,4,5-tetrakisphosphate. We now present direct evidence that the
      putative rat IP3 3-kinase B is genuinely an IP3 3-kinase. We also show that the
      enzyme exists both as a peripheral membrane protein tightly associated with the
      cytosolic face of the extended endoplasmic reticulum network, and as a cytosolic
      protein. Association of the IP3 3-kinase with membranes is not affected by
      treatment with brefeldin A, Na2CO3 (pH 11.5), 2 M NaCl, or alteration of [Ca2+].
      However, treatment of isolated membranes with 4 M urea leads to dissociation of
      the kinase from the membrane, implying that membrane association involves
      specific, conformation-dependent protein-protein interactions. The fact that IP3
      3-kinase B is localized exclusively to membranes of Ca2+ stores, is consistent
      with a model where this kinase plays a role in IP3-dependent Ca2+ release.

PMID- 9182722
TI  - Interaction of truncated human interferon gamma variants with the interferon
      gamma receptor: crucial importance of Arg-129.
AB  - Recombinant human interferon gamma (IFN-gamma), produced in Escherichia coli, was
      selectively truncated at its C-terminus with chymotrypsin, clostripain or
      plasmin. The C-terminal amino acid residues of the three truncated IFN-gamma
      variants were identified as Phe136, Arg129 and Lys128, indicating the removal of
      7, 14 and 15 amino acid residues from the full-length molecule. The absence of
      seven C-terminal residues did not influence the binding of IFN-gamma to its
      receptor. In contrast, the truncation of 14 residues resulted in a decrease in
      the Ka value to 1/24, as determined by surface plasmon resonance analysis. The
      removal of one additional amino acid residue from the C-terminal region of IFN
      gamma led to a marked loss of receptor-binding capacity and biological activity.
      These observations demonstrate that Arg129 is an essential part of a functionally
      important C-terminal IFN-gamma sequence that is involved in receptor interaction.

PMID- 9182723
TI  - Dynamic equilibrium between calcineurin and kinase activities regulates the
      phosphorylation state and localization of the nuclear factor of activated T
      cells.
AB  - The nuclear factor of activated T-cells (NFATp) is a phosphorylated transcription
      factor that resides in the cytoplasm of unactivated T-cells. T-cell activation
      results in the activation of the phosphatase calcineurin (CaN), which leads to
      the dephosphorylation and subsequent nuclear localization of NFATp. We have
      investigated the role of kinases in the phosphorylation state and subcellular
      localization of NFATp. The phosphorylation state and nuclear/cytoplasmic location
      of NFATp were determined in unstimulated murine HT-2 cells treated with a panel
      of kinase inhibitors. Two of the seven kinase inhibitors, staurosporine (St) and
      bisindolylmaleimide I (BI), resulted in the dephosphorylation and nuclear
      localization of NFATp. These St-induced effects were inhibited by pretreatment
      with FK506, indicating that CaN activity was required for the observed effects on
      NFATp. Treatment of cells with ionomycin resulted in NFATp dephosphorylation and
      nuclear localization. Removal of ionomycin from the cells resulted in the
      reappearance of phosphorylated NFATp in the cytosol. St and BI also inhibited the
      re-accumulation of NFATp in the cytoplasm and its re-phosphorylation after
      ionomycin removal. The re-accumulation of NFATp in the cytosol after ionomycin
      withdrawal was shown to be energy- and temperature-dependent. Taken together,
      these results suggest that in unstimulated cells NFATp is actively maintained in
      the cytoplasm by kinases acting in opposition to basal CaN activity.

PMID- 9182724
TI  - Insulin and insulin-like growth factor 1 antagonize the stimulation of ob gene
      expression by dexamethasone in cultured rat adipose tissue.
AB  - The ob gene, specifically expressed in fat cells, encodes leptin, a hormone that
      induces satiety and increases energy expenditure. In this study, we investigated
      the interactions between glucocorticoids and insulin on ob gene expression in
      cultured explants of rat adipose tissue. Only low levels of ob mRNA were detected
      when adipose tissue from fasted rats was cultured for 12-24 h in minimal
      essential medium. However, the addition of dexamethasone to the medium increased
      ob gene expression in a concentration-dependent manner (EC50 10 nM). With 1
      microM dexamethasone, ob mRNA levels were similar to those in fresh fat pads from
      fed rats, reaching a maximum after 12 h. The effect of dexamethasone was blocked
      by actinomycin D, which indicates an action on transcription. This effect was
      increased when a minimum amount of fuel (glucose or a mixture of lactate and
      pyruvate) was supplied in the medium. Unlike dexamethasone, insulin, even when
      combined with high glucose concentrations, did not induce ob expression, although
      it strongly increased the accumulation of mRNA species for fatty acid synthase
      (FAS), the insulin-sensitive glucose transporter GLUT4 and the gamma isoform of
      peroxisome proliferator-activated receptor (PPARgamma). Unexpectedly, insulin
      dose-dependently inhibited dexamethasone-induced ob mRNA accumulation. This
      effect was observed at low concentrations of insulin (IC50 1 nM) and was delayed
      in onset, beginning after 6-9 h of culture. It was mimicked by insulin-like
      growth factor 1 (IGF-1) (100 nM). The inhibition by insulin was only detectable
      when fuels were present and/or when a critical level of ob expression was
      reached. As this inhibitory effect was reversed by cycloheximide, this suggests
      that it required ongoing protein synthesis. In conclusion, unlike dexamethasone,
      insulin had no direct stimulatory effect on ob gene expression. On the other
      hand, insulin (and IGF-1) even inhibited the dexamethasone-induced accumulation
      of ob mRNA. The underlying mechanism involved ongoing synthesis of an inhibitory
      protein by insulin, which is in keeping with its delayed effect. Moreover, the
      expression of genes for FAS, GLUT4 and PPARgamma may be inversely related to that
      of ob.

PMID- 9182725
TI  - Transcriptional activity of the human tissue inhibitor of metalloproteinases 1
      (TIMP-1) gene in fibroblasts involves elements in the promoter, exon 1 and intron
      1.
AB  - The active forms of all of the matrix metalloproteinases (MMPs) are inhibited by
      a family of specific inhibitors, the tissue inhibitors of metalloproteinases
      (TIMPs). Inhibition represents a major level of control of MMP activity. A
      detailed knowledge of the mechanisms controlling TIMP gene expression is
      therefore important. We have isolated a genomic clone of the human TIMP-1 gene. A
      3 kbp XbaI fragment has been sequenced; this fragment contains 1718 bp 5'
      flanking sequences, exon 1, a 929 bp intron 1 and part of exon 2. Computer
      analysis reveals 10 consensus sequences for Sp1, six for activating protein 1 (AP
      1), six for polyoma enhancer A3 (PEA3), 12 for AP-2 and five CCAAT boxes. The
      region hybridizing with a murine TIMP-1 promoter fragment has been subcloned and
      analysed further. RNase protection identifies six transcription start points,
      making exon 1 up to 48 bp in length. Transient transfection of promoter
      chloramphenicol O-acetyltransferase reporter constructs into primary human
      connective tissue fibroblasts shows that a 904 bp fragment that hybridizes to a
      murine TIMP-1 promoter fragment contains a functional promoter. Constructs of 
      738/+95 to -194/+21 are inducible with serum or phorbol ester to a similar extent
      to the endogenous TIMP-1 gene. These results and further mapping with 5' deletion
      mutants from the -738/+95 region have demonstrated that an AP-1 site at -92/-86
      is essential for basal expression of the gene. Point mutations within this region
      have further confirmed the role of this site, along with a more minor role for a
      neighbouring PEA3 site, in basal expression. Deletions from the 3' end also
      implicate a region across the exon 1/intron 1 boundary and especially +21 to +58
      in basal expression. The +21/+58 region contains a putative binding site for the
      transcription factor leader-binding protein 1 (LBP-1). Gel-shift analysis shows
      that protein binds specifically to this region, but competition studies suggest
      that it is unlikely to be LBP-1.

PMID- 9182726
TI  - A soluble 3-hydroxy-3-methylglutaryl-CoA reductase in the protozoan Trypanosoma
      cruzi.
AB  - We report the isolation and characterization of a genomic clone containing the
      open reading frame sequence for 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA)
      reductase from Trypanosoma cruzi, the causative agent of Chagas' disease. The
      protozoan gene encoded for a smaller polypeptide than the rest of the genes
      described from eukaryotic organisms and the deduced amino acid sequence could be
      aligned with the C-terminal half of animal and plant reductases exhibiting
      pronounced similarity to other eukaryotic counterparts. Further examination of
      the 5' flanking region by cDNA analysis and establishment of the splice acceptor
      sites clearly indicated that the corresponding mRNA apparently lacks sequences
      encoding a membrane N-terminal domain. The reductase gene is a single copy and is
      located on a chromosome of 1.36 Mb as determined by contour-clamped homogeneous
      electric field electrophoresis. The overall cellular distribution of enzymic
      activity was investigated after differential centrifugation of Trypanosoma cell
      extracts. Reductase activity was primarily associated with the cellular soluble
      fraction because 95% of the total cellular activity was recovered in the
      supernatant and was particularly sensitive to proteolytic inactivation.
      Furthermore the enzyme can be efficiently overexpressed in a highly active form
      by using the expression vector pET-11c. Thus Trypanosoma cruzi HMG-CoA reductase
      is unique in the sense that it totally lacks the membrane-spanning sequences
      present in all eukaryotic HMG-CoA reductases so far characterized.

PMID- 9182727
TI  - Asymmetrical distribution of cardiolipin in yeast inner mitochondrial membrane
      triggered by carbon catabolite repression.
AB  - Transmembrane asymmetry of cardiolipin in yeast was monitored during the switch
      from fermentative to gluconeogenic growth and the reverse. As soon as cells used
      ethanol as an electron donor to produce ATP by oxidative phosphorylation, rapid
      and abundant cardiolipin synthesis was observed on the matrix side of the inner
      mitochondrial membrane followed by a transverse rearrangement between the two
      leaflets. The cardiolipin distribution changed from about 20:80 (in/out) to 70:30
      (in/out), and after translocation towards the outer leaflet it finally became
      37:63 (in/out). At the same time, cytochrome c oxidase activity remained stable,
      then increased as a possible result of the topographical rearrangement. During
      the reverse process from gluconeogenic to fermentative growth, the amount of
      cardiolipin rapidly decreased by half, its bilayer distribution apparently
      changing to a monolayer organization before the 20:80 (in/out) asymmetry of
      repressed cells was re-established. Experimental impairment of cardiolipin
      topography by antibiotic inhibition of gene expression or in situ dissipation of
      mitochondrial membrane potential produced data that prove that the amount and
      transmembrane distribution of the phospholipid are two specific parameters of the
      mitochondrial inner membrane organization in both fermentative (2.2 fmol/cell and
      20:80, in/out) and gluconeogenic (4.2 fmol/cell and 37:63, in/out) growing yeast
      cells. Finally, the inner mitochondrial membrane topography of cardiolipin
      appeared to be closely associated with the transmembrane redox potential.

PMID- 9182728
TI  - Subcellular structure containing mRNA for beta subunit of mitochondrial H+-ATP
      synthase in rat hepatocytes is translationally active.
AB  - We have recently reported that the nuclear-encoded mRNA for the beta subunit of
      mitochondrial H+-ATP synthase (beta-mRNA) is localized in rounded, electron-dense
      clusters in the cytoplasm of rat hepatocytes. Clusters of beta-mRNA are often
      found in close proximity to mitochondria. These findings suggested a role for
      these structures in controlling the cytoplasmic expression and sorting of the
      encoded mitochondrial precursor. Here we have addressed the question of whether
      the structures containing beta-mRNA are translationally active. For this purpose
      a combination of high-resolution in situ hybridization and immunocytochemical
      procedures was used. Three different co-localization criteria showed that beta
      mRNA-containing structures always revealed positive immunoreactive signals for
      mitochondrial H+-ATP synthase (F1-ATPase), ribosomal and hsc70 proteins.
      Furthermore, clusters show evidence in situ of developmental changes in the
      translational efficiency of the beta-mRNA. These findings suggest that structures
      containing beta-mRNA are translationally active irrespective of their cytoplasmic
      location. The immunocytochemical quantification of the cytoplasmic presentation
      of hsc70 in the hepatocyte reveals that approx. 86% of the protein has a
      dispersed distribution pattern. However, the remaining hsc70 is presented in
      clusters of which only half reveal positive hybridization for beta-mRNA. The
      interaction of hsc70 with the beta-F1-ATPase precursor protein is documented by
      the co-localization of F1-ATPase immunoreactive material within cytoplasmic
      clusters of hsc70 and by the co-immunoprecipitation of hsc70 with the beta
      subunit precursor from liver post-mitochondrial supernatants. Taken together,
      these results suggest a role for hsc70 in the translation/sorting pathway of the
      mammalian precursor of the beta-F1-ATPase protein.

PMID- 9182729
TI  - Phospholipase C inhibitor, U73122, releases intracellular Ca2+, potentiates
      Ins(1,4,5)P3-mediated Ca2+ release and directly activates ion channels in mouse
      pancreatic acinar cells.
AB  - It is recognized in many cellular systems that the receptor/G-protein activation
      of phospholipase C and Ins(1,4,5)P3 production is the transduction pathway
      regulating the release of Ca2+ from internal stores. Ca2+ signals can now be
      monitored at the level of single cells but the biochemical detection of
      Ins(1,4,5)P3 cannot match this resolution. It is often difficult or impossible to
      directly attribute responses evoked in single cells by putative phospholipase C
      coupled agonists to changes in Ins(1,4,5)P3 levels. U73122 is an aminosteroid
      that is reported to act as a specific inhibitor of phospholipase C and it has
      become an important tool in establishing the link between phospholipase C
      activation and cellular Ca2+ signalling. In the present study we use both patch
      clamp electrophysiology and the imaging of fluorescent Ca2+ indicators to
      investigate the effect of U73122 in mouse pancreatic acinar cells. The study
      reveals that U73122 has effects other than the inhibition of phospholipase C.
      U73122 can directly activate ion channels. It can itself promote the release of
      Ca2+ from intracellular stores in permeabilized cells and in intact cells it
      triggers a release of Ca2+ that is initiated specifically at the secretory pole
      of these morphologically and functionally polarized cells. We also present
      evidence that U73122 can potentiate the response to Ins(1,4,5)P3; this is seen
      both in permeabilized cells and in patch-clamp protocols in which cells are
      internally dialysed with submaximal concentrations of Ins(1,4,5)P3. The effects
      of U73122 are therefore multiple and not specific for the inhibition of
      phospholipase C. Importantly, all the effects described influence Ca2+ signalling
      yet in many experimental protocols some of these effects can go unnoticed and
      might in error be attributed simply to the inhibition of Ins(1,4,5)P3 production.

PMID- 9182730
TI  - Interleukin 1-induced calcium signalling in chondrocytes requires focal
      adhesions.
AB  - The cytokine interleukin 1 (IL-1) is an important mediator of connective-tissue
      destruction in arthritic joints but the mechanisms by which IL-1 mediates signal
      transduction in chondrocytes is poorly understood. Previous results have
      indicated that IL-1 receptors co-localize with focal adhesions [Qwarnstrom, Page,
      Gillis and Dower (1988) J. Biol. Chem. 263, 8261-8269], discrete adhesive domains
      of cells that function in cell attachment and possibly in signal transduction. We
      have determined whether focal adhesions restrict IL-1-induced Ca2+ signalling in
      primary cultures of bovine chondrocytes. In cells grown for 24 h on fibronectin,
      the basal intracellular Ca2+ ion concentration ([Ca2+]i) was 100+/-3 nM. Optimal
      increases of [Ca2+]i above baseline were induced by 10 nM IL-1 (183+/-30 nM above
      baseline). There was no significant difference between cells plated on
      fibronectin or type II collagen (P>0.2; 233+/-90 nM above baseline). Ca2+
      transients were significantly decreased by the inclusion of 0.5 mM EGTA in the
      bathing buffer (74+/-11 nM above baseline), and 1 microM thapsigargin completely
      blocked Ca2+ transients. Cells plated on poly-(l-lysine) or suspended cells
      showed no Ca2+ increases, whereas cells grown on fibronectin exhibited IL-1
      induced Ca2+ responses that corresponded temporally to the time-dependent cell
      spreading after plating on fibronectin. Cells plated on poly-(l-lysine) and
      incubated with fibronectin-coated beads exhibited vinculin staining in
      association with the beads. In identical cell preparations, IL-1 induced a 136+/
      39 nM increase of [Ca2+]i above baseline in response to 10 nM IL-1beta. There
      were no IL-1-induced Ca2+ increases when cells on poly-(l-lysine) were incubated
      with fibronectin-coated beads for only 15 min at 37 degrees C, in cells
      maintained for 3 h at 4 degrees C, in cells incubated with BSA beads for 3 h at
      37 degrees C, or in cells pretreated with cytochalasin D. Labelling of IL-1
      receptors with 125I-IL-1beta showed 3-fold more specific labelling of focal
      adhesion complexes in cells incubated with fibronectin-coated beads compared with
      cells incubated with BSA-coated beads, indicating that IL-1 receptor binding or
      the number of IL-1 receptors was increased in focal adhesions. These results
      indicate that, in chondrocytes, IL-1-induced Ca2+ signalling is dependent on
      focal adhesion formation and that focal adhesions recruit IL-1 receptors by
      redistribution in the cell membrane.

PMID- 9182731
TI  - Structural and functional analysis of a glutathione S-transferase from Ascaris
      suum.
AB  - A recombinant glutathione S-transferase (GST) (EC 2.5.1.18) from the parasitic
      nematode Ascaris suum (AsGST1) displays specific activity with a variety of model
      substrates and secondary products of lipid peroxidation. The AsGST1 interacts
      with a range of model inhibitors, haematin-related compounds, bile acids and
      anthelminthics. The reported variations in biochemical activity correlate with
      structural differences observed by homology modelling. Here, differences in the
      topography of the proposed substrate binding site between the AsGST1 and the host
      GSTs were identified. A rabbit polyclonal antiserum was raised against the
      glutathione-binding proteins of A. suum and specific antibodies against AsGST1
      were affinity-purified using the recombinant protein. These antibodies were used
      to localize the AsGST1 in adult worms by immunohistochemical staining. The
      strongest immunostaining for AsGST1 was localized in the intestine in all worms
      examined. This suggests that the enzyme may be responsible for the metabolism of
      materials that are incorporated from the environment, as well as for molecules
      that are excreted or secreted from the parasite to the environment. It also
      demonstrates the accessibility of the enzyme to an inhibitor or blocking
      antibody. In addition, the structure and sequence of the gene encoding AsGST1
      have been determined. Southern-blot analyses of the AsGST1 gene suggests that it
      is a single-copy gene. The nucleotide sequence analysis revealed that the gene is
      composed of four exons and three introns, and potential regulatory elements were
      identified in the 5' flanking sequence.

PMID- 9182732
TI  - Genetic information 'created' by archaebacterial DNA polymerase.
AB  - DNA polymerase catalyses replication of cellular DNA. The reaction requires a
      primer-template complex, and a new DNA chain grows from the 3' end of the primer
      along the template; no genetic information is created in this reaction. We
      demonstrate that DNA polymerase from Thermococcus litoralis, a hyperthermophilic
      marine Archaea, can synthesize up to 50000 bp of linear double-stranded DNA in
      the complete absence of a primer-template complex, indicating that genetic
      information is 'created.' The possibility of DNA contamination in the reaction
      mixture, which may serve as a primer and/or template, was vigorously excluded;
      for example, pretreatment of DNA polymerase with DNase I or extensive
      chromatographic purification of the substrate, deoxyribonucleoside 5'
      triphosphates, did not abolish the primer-template-independent DNA synthesis. The
      DNA synthesized was (CTAGATAT)n, (TAGATATCTATC)n or a related sequence. Similar
      repetitive sequences are found in centromeric satellite DNA of many organisms.
      The significance of this ab initio DNA synthesis is that genetic information can
      flow from protein to DNA.

PMID- 9182733
TI  - Selective binding of N-acetylglucosamine to the chicken hepatic lectin.
AB  - Among Ca2+-dependent (C-type) animal lectins, the chicken hepatic lectin (CHL) is
      unique in displaying almost complete selectivity for N-acetylglucosamine over
      other monosaccharide ligands. The crystal structures of the carbohydrate
      recognition domain (CRD) from serum mannose-binding protein (MBP) and of a
      complex between the CRD from liver MBP and the methyl glycoside of N
      acetylglucosamine were used to model the binding site in CHL. Substitution of
      portions of CHL into the MBP framework did not substantially increase
      selectivity. A bacterial expression system for the CRD of CHL was developed so
      that specific residues predicted to be near the 2-acetamido substituent of N
      acetylglucosamine could be altered by site-directed mutagenesis. The results
      indicate that the ligand is bound to CHL in the same orientation as it binds to
      liver MBP. A tyrosine and a valine residue that probably contact the the N-acetyl
      group have been identified. These results, together with studies of ligand
      binding selectivity, suggest that these residues form part of a binding pocket
      for the N-acetyl group, which confers selective binding of N-acetylglucosamine.

PMID- 9182735
TI  - Cross-linking analysis of the ryanodine receptor and alpha1-dihydropyridine
      receptor in rabbit skeletal muscle triads.
AB  - In mature skeletal muscle, excitation-contraction (EC) coupling is thought to be
      mediated by direct physical interactions between the transverse tubular, voltage
      sensing dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR) Ca2+
      release channel of the sarcoplasmic reticulum (SR). Although previous attempts at
      demonstrating interactions between purified RyR and alpha1-DHPR have failed, the
      cross-linking analysis shown here indicates low-level complex formation between
      the SR RyR and the junctional alpha1-DHPR. After cross-linking of membranes
      highly enriched in triads with dithiobis-succinimidyl propionate, distinct
      complexes of more than 3000 kDa were detected. This agrees with numerous
      physiological and electron-microscopic findings, as well as co
      immunoprecipitation experiments with triad receptors and receptor domain-binding
      studies. However, a distinct overlap of immunoreactivity between receptors was
      not observed in crude microsomal preparations, indicating that the triad complex
      is probably of low abundance. Disulphide-bonded, high-molecular-mass clusters of
      triadin, the junctional protein proposed to mediate interactions in triads, were
      confirmed to be linked to the RyR. Calsequestrin and the SR Ca2+-ATPase were not
      found in cross-linked complexes of the RyR and alpha1-DHPR. Thus, whereas recent
      studies indicate that the two receptors exhibit temporal differences in their
      developmental inductions and that receptor interactions are not essential for the
      formation and maintenance of triads, this study supports the signal transduction
      hypothesis of direct physical interactions between triad receptors in adult
      skeletal muscle.

PMID- 9182736
TI  - Bacterial transmission in periodontal diseases: a critical review.
AB  - This review paper addresses intra- and extra-familial transfer of bacteria
      associated with periodontal diseases. Recent advances in molecular biology
      provide sensitive methods to differentiate organisms within the same species,
      thereby facilitating tracking routes of their transmission. Evidence for the
      passing of microorganisms between parents and children is particularly strong. In
      this regard, molecular genetic techniques have demonstrated that if a child is
      colonized by a potentially pathogenic species, then one of the parents will
      usually harbor genotypically identical bacteria. The data also indicate that
      transfer of bacteria between spouses occur, but it appears to happen
      infrequently. Saliva appears to be a major vector for bacterial transmission.
      However, the transfer of organisms does not necessarily result in colonization or
      infection of the host. Furthermore, individuals who harbor putative pathogens
      frequently do not manifest any signs of periodontal disease. This is attributed
      to host defenses, bacterial antagonism, and possibly lack of pathogenicity of
      infecting organisms. It is concluded, based upon current evidence, that
      periodontal pathogens are communicable; however, they are not readily
      transmissible.

PMID- 9182734
TI  - Properties of a cysteine-free proton-pumping nicotinamide nucleotide
      transhydrogenase.
AB  - Nicotinamide nucleotide transhydrogenase from Escherichia coli was investigated
      with respect to the roles of its cysteine residues. This enzyme contains seven
      cysteines, of which five are located in the alpha subunit and two are in the beta
      subunit. All cysteines were replaced by site-directed mutagenesis. The final
      construct (alphaC292T, alphaC339T, alphaC395S, alphaC397T, alphaC435S, betaC147S,
      betaC260S) was inserted normally in the membrane and underwent the normal NADPH
      dependent conformational change of the beta subunit to a trypsin-sensitive state.
      Reduction of NADP+ by NADH driven by ATP hydrolysis or respiration was between
      32% and 65% of the corresponding wild-type activities. Likewise, the catalytic
      and proton pumping activities of the purified cysteine-free enzyme were at least
      30% of the purified wild-type enzyme activities. The H+/H- ratio for both enzymes
      was 0.5, although the cysteine-free enzyme appeared to be more stable than the
      wild-type enzyme in proteoliposomes. No bound NADP(H) was detected in the
      enzymes. Modification of transhydrogenase by diethyl pyrocarbonate and the
      subsequent inhibition of the enzyme were unaffected by removal of the cysteines,
      indicating a lack of involvement of cysteines in this process. Replacement of
      cysteine residues in the alpha subunit resulted in no or little change in
      activity, suggesting that the basis for the decreased activity was probably the
      modification of the conserved beta-subunit residue Cys-260 or (less likely) the
      non-conserved beta-subunit residue Cys-147. It is concluded that the cysteine
      free transhydrogenase is structurally and mechanistically very similar to the
      wild-type enzyme, with minor modifications of the properties of the NADP(H) site,
      possibly mediated by the betaC260S mutation. The cysteine-free construct will be
      a valuable tool for studying structure-function relationships of
      transhydrogenases.

PMID- 9182737
TI  - Progressive cervical root resorption related to tetracycline root conditioning.
AB  - Root resorption is reported as a microscopic finding in trials attempting to
      regenerate the periodontium using tetracycline or citric acid root conditioning.
      This report deals with a case of progressive cervical root resorption in a female
      patient who had been successfully treated by tetracycline root conditioning. The
      article emphasizes the possibility of this adverse effect, and discusses a
      possible mechanism inducing this phenomenon.

PMID- 9182738
TI  - Clinical evaluation of the speed and effectiveness of subgingival calculus
      removal on single-rooted teeth with diamond-coated ultrasonic tips.
AB  - Several studies have found incomplete calculus removal during periodontal
      treatment with traditional hand curets, sonic, and ultrasonic instruments. This
      study evaluated the speed and effectiveness of subgingival calculus removal with
      new diamond-coated ultrasonic tips on single-rooted teeth. Single session
      subgingival scaling and root planing was performed on 80 teeth with 5 to 12 mm
      probing depths in 15 patients. Each patient provided groups of 4 teeth that were
      randomly treated with either hand curets (HAND); standard smooth ultrasonic tip
      (US); or fine grit (FINDIAM) or medium grit (MEDDIAM) diamond-coated ultrasonic
      tips. The time taken to reach the therapeutic endpoint of a clean, smooth root
      surface in a defined region on each tooth with each instrument by the 3
      therapists with differing experience levels was recorded. The teeth were then
      atraumatically extracted, stored in a surfactant, photographed at 10X, and the
      percent of calculus present in the area of the pocket or on a comparable control
      surface calculated by histometric point counting. ANOVA and paired t tests showed
      that mean percent remaining calculus on treated versus control surfaces was HAND
      4.6 +/- 5.3 versus 57.5 +/- 28.2, US 4.7 +/- 6.4 versus 54.4 +/- 25.9, FINDIAM
      4.3 +/- 5.2 versus 37.5 +/- 22.1, and MEDDIAM 3.4 +/- 4.2 versus 50.7 +/- 20.1,
      respectively (all P < 0.01). The mean time in seconds to reach the clinical
      endpoint ranged from HAND 289 +/- 193, US 194 +/- 67, FINDIAM 167 +/- 71, to
      MEDDIAM 147 +/- 92. All powered instruments were significantly faster than HAND
      (P < 0.05), but did not differ from each other. On a 0 = "smooth" to 3 = "rough"
      scale, most often HAND resulted in "smooth" surfaces (10/20), the powered tips of
      all types "slight" surface roughness (10/20 each), and US the most "moderate"
      roughness (7/20). There were no differences in percent calculus remaining,
      surface roughness, or time spent among the 3 treating clinicians despite their
      varying experience levels. The results of this study showed that percent calculus
      remaining was <5% with all the instruments given time ad libitum on a given root
      surface. Root roughness was generally slightly greater with all 3 powered tips.
      All of the powered instruments took significantly less time than the HAND. Both
      DIAM tips took less time than US. Diamond-coated ultrasonic tips appeared to be
      much more efficient than HAND or US in removing calculus in moderate-deep probing
      depths on single-rooted teeth in vivo.

PMID- 9182739
TI  - Comparative effects of cyclosporin on glycosaminoglycan synthesis by gingival
      fibroblasts.
AB  - Histological studies show that drug-induced gingival overgrowth results from an
      accumulation of the connective tissue component. Despite comprising a major part
      of gingival connective tissue, a role for glycosaminoglycans (GAGs) in the
      pathogenesis of gingival overgrowth has received scant attention. By analyzing
      the metabolism of 3H-glucosamine, we have compared GAG and hyaluronan synthesis
      by fibroblasts derived from normal and overgrown gingival tissue, and the effects
      of cyclosporin on GAG output. GAG production was cell density-dependent,
      fibroblasts cultured at low density synthesizing significantly increased
      quantities in comparison to confluent cultures. The effects of cyclosporin on GAG
      synthesis was also found to be both cell density- and cell strain-dependent.
      However, cyclosporin-stimulated GAG synthesis by 2/3 overgrown cell strains and
      1/3 normal strains. These results suggest that a direct promotion of GAG
      synthesis by gingival fibroblasts in response to cyclosporin may play a role in
      the pathogenesis of gingival overgrowth.

PMID- 9182740
TI  - A short-term study of the effects of SBHAN, a novel compound, on gingival
      inflammation in the beagle dog.
AB  - Unique hydroxyl ion-modulating compounds based on the amino acid glycine have
      been developed that possess both antimicrobial and pro-healing properties. The
      purpose of the present study was to determine the effects of one of these
      compounds, 8.5% (w/v) sodium N, N-bis-2 (hydroxylethyl) aminoacetate (SBHA) with
      0.3% (w/v) NaOH (SBHAN) on ligature-induced gingival inflammation in the beagle
      dog. Fifteen purebred beagle dogs were subjected to a 14-day oral hygiene
      regimen, consisting of manual scaling and daily toothbrushing with plain pumice.
      Gingival inflammation was then initiated by tying ligatures around 12 study teeth
      per dog and by placing the dogs on water-softened dog chow. After 30 days,
      ligatures were removed, dogs were placed on a hard diet and randomly assigned to
      five treatment groups by the flip of two coins. The five treatments included: 1)
      distilled, pyrogen-free water; 2) 8.5% (w/v) SBHAN; 3) 4.3% (w/v) SBHAN; 4) 0.12%
      chlorhexidine; and 5) 8.5% SBHA (w/v) (SBHAN without added NaOH). Solutions were
      placed in opaque spray bottles to shield their identity from the examiner.
      Treatment consisted of a daily aerosol application of 2 ml of each solution in a
      calibrated spray bottle to the affected teeth. The following measures were taken
      from the dogs at baseline (after hygienic phase), 30 days after initiation of
      gingival inflammation (before ligature removal), and 2 weeks and 4 weeks after
      ligature removal: 1) plaque index (PI); 2) gingival index (GI); 3) probing depths
      (PD); 4) relative attachment levels (RAL); and 5) gingival crevicular fluid
      volume (GCF). Analysis of subgingival plaque for anaerobic and aerobic colony
      forming units/ml was also performed at each time point. Gingival biopsies were
      performed, sectioned and stained with hematoxylin and eosin to quantify the
      inflammatory cell infiltrate (ICI). After ligature placement, increases were
      observed in PI, GI, PD, RAL, GCF, aerobic and anaerobic subgingival microbial
      counts, and ICI. After ligature removal, spontaneous resolution of gingival
      inflammation and plaque accumulation around the teeth of all dogs was observed
      with any treatment. Statistical analysis (Tukey's pairwise comparisons) of the
      mean PI, GI, PD, RAL, ICI, and GCF after 4 weeks of treatment with each agent,
      however, revealed that 8.5% SBHAN was significantly (P < 0.05) more effective
      than water, 4.3% SBHAN, or 8.5% SBHA in reducing PI, GI, PD, and GCF, but not RAL
      or ICI. Moreover, 0.12% chlorhexidine was more effective than water, 4.3% SBHAN,
      or 8.5% SBHA at reducing GI, PD, and GCF, but not PI, RAL, or ICI. No adverse
      reactions to the SBHAN were observed visually or histologically in any of the
      dogs during the course of the investigation. These data suggest that further
      investigation in a larger study population of the potential of SBHAN as an anti
      gingivitis compound is warranted.

PMID- 9182741
TI  - Option-4 algorithm for automated disc probe: reduction in the variance of site
      specific relative attachment level measurements.
AB  - Physical periodontal measurement is plagued by many confounders which result in
      aberrant values. Replicate measurements can reduce the number of aberrant values,
      the measurement error, and the variance of site-specific measurements. This study
      aimed to reduce the variance of site-specific measurements by using a new
      clinical algorithm (the Option-4 algorithm) for an automated disk probe. A single
      clinician recorded full-mouth relative attachment levels (RAL) at one visit in 32
      patients (mean age 45.5 years) with moderately advanced chronic adult
      periodontitis. RAL was recorded over two passes at six sites per tooth (4,675
      sites). The algorithm accepted the first and second pass RALs (RAL1 and RAL2) if
      their difference was < or = 1 mm, otherwise a maximum of two further RALs (RAL3
      and RAL4) were recorded until the difference between any two RALs was < or = 1 mm
      (SAL1 and SAL2): 4,048 sites (86.6%) required two recordings, 580 sites (12.4%)
      required three recordings and 47 sites (1%) required four recordings. Correlation
      coefficients for RAL1 and RAL2 and SAL1 and SAL2 (4,675 sites) were both > or =
      0.91 (P = 0.00). Site-specific variances were calculated for RAL1 and RAL2 and
      SAL1 and SAL2. The mean of the RAL1/RAL2 site-specific variances (A) was 0.45 mm2
      (range 0.00 mm2 to 35.28 mm2) whilst the mean of the SAL1/SAL2 variances (B) was
      0.09 mm2 (range 0.00 mm2 to 0.5 mm2): the respective medians were 0.08 mm2 and
      0.02 mm2. The study demonstrated high intra-examiner RAL reproducibility. The
      Option-4 algorithm produced an 80% reduction in the mean site-specific variance
      of RAL1/RAL2 (Y) and a 75% reduction in the median site-specific variance of
      RAL1/RAL2 (y = [(A - B)/A] x 100).

PMID- 9182742
TI  - The effect of smoking on mechanical and antimicrobial periodontal therapy.
AB  - The aim of this investigation was to evaluate the effect of smoking on the
      outcome of periodontal therapy. The study consisted of 54 patients who
      participated in a 4-group parallel-arm clinical trial on the efficacy of three
      locally delivered antimicrobial systems as adjuncts to scaling and root planing
      in the treatment of sites with persistent pocketing after a course of scaling and
      root planing. These groups included scaling and root planing either alone (S) (n
      = 3), or in conjunction with the application of 25% tetracycline fibers (S&T) (n
      = 13), 2% minocycline gel (S&Mi) (n = 14), or 25% metronidazole gel (S&Me) (n =
      14). In each patient four pockets > 5 mm with bleeding on probing (BOP) and/or
      suppuration were studied. The number of subjects who smoked was: 8 (61.5%) in the
      S&T group, 8 (57.1%) in the S&Mi group, 6 (42.9%) in the S&Me group, and 6
      (46.2%) in the S group. The probing depth, attachment level and other clinical
      parameters were assessed at baseline and 6 weeks after treatments. The clinical
      results of this comparative study have been previously reported. Regardless of
      the type of treatment, the change in the probing depth (delta PD) and attachment
      gain (delta AL) were greater in non-smoker subjects than smoker subjects. delta
      PD was 1.14 mm versus 0.76 mm (P = 0.019), and delta AL was 0.52 mm versus 0.50
      mm at (P = 0.845) for non-smokers and smokers respectively. The analysis of
      variance using the general linear model (GLM) was used for delta PD and delta AL
      and took into account the variations in the treatments, number of smoker subjects
      per group, and baseline probing depth. There was a significant interaction
      between the "smoking" and the "baseline PD." Further analysis using linear
      regression indicated that, while there was a significant relationship between the
      baseline PD and the delta PD or delta AL among the non-smokers, weak and
      insignificant relationship existed among the smoker subjects. Thus, smoking may
      have an important role in determining the prognosis of periodontal treatment,
      particularly in persistent and deep pockets.

PMID- 9182743
TI  - Periodontal findings in Cohen syndrome with chronic neutropenia.
AB  - Radiographic periodontal status and microbiological findings of periodontal
      pockets in subjects with Cohen syndrome are presented in this report. This
      hereditary disorder causes mental retardation, and neutropenia is one feature of
      the syndrome. Fifteen patients with Cohen syndrome and 15 controls matched for
      age and sex and, as far as possible, according to the degree of mental
      retardation were examined. Alveolar bone loss was evaluated from the panoramic
      radiographs. Two subgingival samples were obtained from the most affected
      anterior and posterior periodontal sites in each dentate subject and examined for
      the occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia/nigrescens, Peptostreptococcus micros, Bacteroides
      forsythus, and Campylobacter rectus. Subjects with Cohen syndrome had alveolar
      bone loss more frequently and the bone loss was more extensive (Mann-Whitney U
      test: P < 0.05) than in the controls. They also harbored one or several of the
      putative periodontal pathogens (Mann-Whitney U-test: P < 0.001) more often than
      the controls. We conclude that subjects with Cohen syndrome have increased
      susceptibility to early periodontal breakdown which is likely to be associated
      with neutropenia.

PMID- 9182744
TI  - Odontogenic myxofibroma arising from the periodontal ligament in the maxillary
      molar region.
AB  - A rare case of odontogenic myxofibroma, which arose from the periodontal ligament
      and expanded into the oral cavity resulting in an epulis-like lesion in a 52-year
      old man, is reported including details of studies using lectin histochemistry,
      transmission electron microscopy (TEM), and immunohistochemistry. Most of the
      tumor cells, which appeared spindle-like with abundant rough endoplasmic
      reticulum and some microfilaments by TEM, showed immunoreactivity for mesenchymal
      markers. Some tumor cells, which were polygonal and contained many microfilaments
      and some filament bundles, were immunoreactive for muscle markers. The present
      case was considered to consist of many fibroblasts and some myofibroblasts.

PMID- 9182745
TI  - Cocaine-associated rapid gingival recession and dental erosion. A case report.
AB  - This case report chronicles the clinical presentation and unusual response to
      treatment of a patient with rapid gingival recession and dental erosion secondary
      to local cocaine application. The initial clinical diagnosis was necrotizing
      ulcerative periodontitis; only after several years of therapy did the patient
      voluntarily inform one of the therapists that cocaine had been regularly applied
      to the affected gingival sites. This case illustrates the importance of including
      cocaine application to gingival tissues in a differential diagnosis in cases of
      rapid gingival recession and dental erosion of unknown etiology.

PMID- 9182746
TI  - Guided periodontal tissue regeneration in interproximal intrabony defects
      following treatment with a synthetic bioabsorbable barrier.
AB  - This study evaluated guided periodontal tissue regeneration (GPTR) wound healing
      in interproximal intrabony periodontal defects following surgical treatment with
      a synthetic bioabsorbable barrier made from a copolymer of glycolide and lactide.
      Periodontal lesions were induced around the mandibular central incisor teeth of
      10 adult male rhesus monkeys using orthodontic elastics. Once similar
      contralateral interproximal defects had been created, the elastics were removed
      and an oral hygiene program was initiated and maintained until completion of the
      study. Three weeks after commencing oral hygiene, flap surgery was performed in
      the mandibular incisor region and the root surfaces were thoroughly scaled and
      root planed to the apical portion of the defects. On the test sites, a
      bioabsorbable barrier was placed over the entire interproximal periodontal
      defect. Control sites did not receive a barrier. Five months after surgery, the
      animals were sacrificed and the teeth with their supporting periodontium were
      processed for light microscopic evaluation. Postoperative clinical healing
      progressed uneventfully and was similar in both control and test sites.
      Histologic observations from control specimens indicated reparative healing
      characterized by a long junctional epithelium with limited cementum and bone
      formation. Test specimens exhibited significantly more new connective tissue
      attachment, cementum deposition, and bone formation than the control sites (P <
      0.001). The barriers had been completely resorbed with no apparent adverse effect
      on periodontal wound healing. It was concluded that this bioabsorbable barrier
      facilitated GPTR wound healing in interproximal intrabony periodontal defects.

PMID- 9182747
TI  - Guided periodontal tissue regeneration in Class II furcation defects following
      treatment with a synthetic bioabsorbable barrier.
AB  - The purpose of this study was to evaluate guided periodontal tissue regeneration
      (GPTR) wound healing in Class II furcation defects following surgical treatment
      with a synthetic bioabsorbable barrier manufactured from a copolymer of glycolide
      and lactide. Periodonal lesions were induced in four adult male rhesus monkeys
      around the mandibular first, second, and third molar teeth using orthodontic
      elastics. After obtaining approximately 30% bone loss, the elastics were replaced
      by a stainless steel wire which had a projection extending into the furcation.
      Once similar contralateral Class II furcation defects had been created, the wires
      were removed, and an oral hygiene program was initiated and maintained until
      completion of the study. Three weeks after commencing oral hygiene, flap surgery
      was performed in the mandibular molar region and the root surfaces were
      thoroughly scaled and root planed to the apical portion of the defects. A
      bioabsorbable barrier was then placed to cover the furcation defects on one side
      of the jaw (i.e., test sites). No barriers were placed on the contralateral
      molars (i.e., control sites). Five months after surgery, the animals were
      sacrificed and the teeth with their supporting periodontium were processed for
      light microscopic evaluation. Clinical healing progressed normally and was
      similar in both groups. Histologic observations from control specimens indicated
      repair with epithelium and connective tissue occupying the majority of the
      furcation defects. Test specimens exhibited definitive evidence of regeneration
      with significantly greater new connective tissue attachment, cementum deposition,
      and bone formation than the control sites (P < 0.001). It was concluded that this
      bioabsorbable barrier facilitated GPTR wound healing in Class II furcation
      defects.

PMID- 9182748
TI  - On the status of object concepts in aphasia.
AB  - While verbal comprehension is often impaired in aphasia due to left hemispheric
      damage, the status of nonverbal conceptual knowledge of objects remains
      controversial. We tested 16 aphasic subjects for their comprehension of concrete
      single words. Eight showed significant impairment on word-to-picture matching,
      when distractors were semantically and not just perceptually confusable. These 8
      also made errors in answering verbal probe questions concerning the same items.
      When tested on a nonverbal pictorial version of the same probe questions,
      however, 3 of these 8 improved their performance to the level of normal controls.
      The other 5 showed continuing impairment in indicating responses to pictorial
      probes. These 5 showed no evidence of generalized intellectual impairment, and it
      is concluded that they demonstrated a comprehension deficit not limited to the
      verbal domain. Unlike the other aphasic patients, these latter 5 also had CT scan
      lesions extending into the posterior left temporal lobe (involving Brodmann's
      areas 22, 21, and 37). They were also more impaired in terms of general aphasia
      severity. It is suggested that a nonverbal (as well as verbal) semantic memory
      deficit occurs in a subgroup of patients with single word comprehension
      disturbance due to aphasia, and this may reflect general severity of language
      impairment as well as damage to certain localized brain regions.

PMID- 9182750
TI  - A theory of neurolinguistic development.
AB  - This article offers a developmental theory of language and the neural systems
      that lead to and subserve linguistic capabilities. Early perceptual experience
      and discontinuities in linguistic development suggest that language develops in
      four phases that occur in a fixed, interdependent sequence. In each phase of
      language, a unique ontogenetic function is accomplished. These functions have
      proprietary neural systems that vary in their degree of specialization. Of
      particular interest is an analytical mechanism that is responsible for linguistic
      grammar. This mechanism is time-locked and can only be turned on in the third
      phase. Confirming evidence is provided by children who are delayed in the second
      phase of the language learning process. These children store insufficient lexical
      material to activate their analytic mechanism. Inactivation behaves like damage,
      shifting language functions to homologous mechanisms in the nondominant
      hemisphere, thereby increasing functional and anatomical symmetry across the
      hemispheres. This atypical assembly of neurolinguistic resources produces
      functional but imperfect command of spoken language and may complicate learning
      of written language. The theory thus offers a different role for genetics and
      early experience, and a different interpretation of neuroanatomic findings, from
      those entertained in most other proposals on developmental language disorders.

PMID- 9182749
TI  - Categorical and dimensional decoding of emotional intonations in patients with
      focal brain lesions.
AB  - The present study attempts to elucidate whether cerebral brain lesions
      differentially affect the crossmodal decoding of emotional intonations in
      semantically meaningless sentences. Forty patients with well-documented lesions
      and 12 matched hospital controls participated in the study. Twenty-one had left
      brain damage (LBD: 12 with anterorolandic (anterior) and 9 with retrorolandic
      infrasylvian (posterior) lesions); 19 had right brain damage (RBD: 12 anterior, 7
      posterior lesions). The decoding of emotion categories was measured using (a)
      multiple choice of verbal labels and (b) matching one emotional vocalization
      (joy, fear, sadness, or anger) with two choice facial expressions. Crossmodal
      dimensional decoding was assessed by matching vocalizations with two facial
      expressions with regard to emotional valence or arousal. Results indicate that
      labeling was reduced in all lesion groups as compared to that in controls.
      Crossmodal categorical recognition was impaired in RBD, whereas LBD performance
      was comparable to controls. However, in the dimensional decoding task, a reduced
      recognition of valence in LBD and arousal in RBD was observed. An analysis of
      localizational subgroups revealed that subjects with left ventral frontal
      lesions, which in part extended into the adjacent right hemisphere, were
      predominantly impaired in the crossmodal identification of valence, whereas right
      temporoparietal lesions affected arousal decoding. Our results suggest that
      lateralized lesions may differentially affect the crossmodal recognition of
      dimensional concepts such as valence and arousal.

PMID- 9182751
TI  - Generalization from single sentence to multisentence production in severely
      aphasic patients.
AB  - Multisentence production was examined in three nonfluent aphasic patients who had
      undergone a single sentence production training program using a computerized
      visual communication system (C-VIC). Patients were required to describe
      videotaped vignettes in English and using C-VIC. C-VIC allowed for an
      investigation of production abilities previously impossible to measure in
      severely aphasic patients, since C-VIC does not require internal generation of
      appropriate lexical items or phonological and articulatory realization. Results
      are discussed in the context of language production models in an attempt to
      determine the breakdown(s) in the production system that result in difficulty in
      trying to produce multiple sentences.

PMID- 9182752
TI  - Sno storm in the nucleolus: new roles for myriad small RNPs.

PMID- 9182753
TI  - Switching the model: a concerted mechanism for GTPases in protein targeting.

PMID- 9182754
TI  - The missing bone.

PMID- 9182755
TI  - Anti-neural-inhibition: a conserved mechanism for neural induction.

PMID- 9182756
TI  - Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its
      membrane form.
AB  - The mechanisms by which proteins gain entry into membranes is a fundamental
      problem in biology. Here, we present the first crystal structure of a thiol
      activated cytolysin, perfringolysin O, a member of a large family of toxins that
      kill eukaryotic cells by punching holes in their membranes. The molecule adopts
      an unusually elongated shape rich in beta sheet. We have used electron microscopy
      data to construct a detailed model of the membrane channel form of the toxin. The
      structures reveal a novel mechanism for membrane insertion. Surprisingly, the
      toxin receptor, cholesterol, appears to play multiple roles: targeting, promotion
      of oligomerization, triggering a membrane insertion competent form, and
      stabilizing the membrane pore.

PMID- 9182757
TI  - A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the
      Ras/MAPK signaling pathway.
AB  - Activation of the Ras/MAPK signaling cascade is essential for growth factor
      induced cell proliferation and differentiation. In this report, we describe the
      purification, cloning, and characterization of a novel protein, designated FRS2,
      that is tyrosine phosphorylated and binds to Grb2/Sos in response to FGF or NGF
      stimulation. We find that FRS2 is myristylated and that this modification is
      essential for membrane localization, tyrosine phosphorylation, Grb2/Sos
      recruitment, and MAPK activation. FRS2 functions as a lipid-anchored docking
      protein that targets signaling molecules to the plasma membrane in response to
      FGF stimulation to link receptor activation with the MAPK and other signaling
      pathways essential for cell growth and differentiation. Finally, we demonstrate
      that FRS2 is closely related and probably indentical to SNT, the long-sought
      target of FGF and NGF receptors.

PMID- 9182758
TI  - Empty site forms of the SRP54 and SR alpha GTPases mediate targeting of ribosome
      nascent chain complexes to the endoplasmic reticulum.
AB  - The SRP54 and SR alpha subunits of the signal recognition particle (SRP) and the
      SRP receptor (SR) undergo a tightly coupled GTPase cycle that mediates the signal
      sequence-dependent attachment of ribosomes to the Sec61 complex. Here, we show
      that SRP54 and SR alpha are in the empty site conformation prior to contact
      between the SRP-ribosome complex and the membrane-bound SR. Cooperative binding
      of GTP to SRP54 and SR alpha stabilizes the SRP-SR complex and initiates signal
      sequence transfer from SRP54 to Sec61 alpha. The GTP-bound conformations of SR
      alpha and SRP54 perform distinct roles, with SR alpha performing a predominant
      role in complex stabilization. Hydrolysis by both SRP54 and SR alpha is a
      prerequisite for dissociation of the SRP-SR complex.

PMID- 9182759
TI  - A distinct nuclear import pathway used by ribosomal proteins.
AB  - Protein transport into the nucleus is governed by the interaction of soluble
      transport factors with their import substrates and nuclear pore complexes. Here,
      we identify a major distinct nuclear import pathway, mediated by a previously
      uncharacterized yeast beta karyopherin Kap123p. The predominant substrates for
      this pathway are ribosomal proteins, which must be imported into the nucleus
      prior to assembly into pre-ribosomes. Kap123p binds directly to its transport
      substrates, repeat motif-containing nucleoporins, and Ran-GTP. We show that the
      related protein Pse1p is also a karyopherin and can functionally substitute for
      Kap123p; both are capable of specifically directing a ribosomal nuclear
      localization signal reporter to the nucleus in vivo.

PMID- 9182760
TI  - Kinetochore localization of murine Bub1 is required for normal mitotic timing and
      checkpoint response to spindle damage.
AB  - The mitotic checkpoint ensures proper chromosome segregation by delaying anaphase
      until chromosomes are aligned on the spindle. Following prolonged spindle damage,
      however, cells eventually exit mitosis and undergo apoptosis. We show here that a
      murine homolog of the yeast mitotic checkpoint gene BUB1 localizes to the
      kinetochore during mitosis. By expressing a dominant-negative mutant, we show
      that mBub1 is not only required for the checkpoint response to spindle damage,
      but acts in the timing of a normal mitosis. In addition, when mBub1 function is
      compromised, cells escape apoptosis and continue cell cycle progression, despite
      leaving mitosis with a disrupted spindle. These data demonstrate a role for
      kinetochore-associated mBub1 in regulating exit from mitosis, and suggest
      functional links between the mitotic checkpoint and subsequent apoptotic events
      in G1.

PMID- 9182761
TI  - FCA, a gene controlling flowering time in Arabidopsis, encodes a protein
      containing RNA-binding domains.
AB  - A strong promoter of the transition to flowering in Arabidopsis is encoded by
      FCA. FCA has been cloned and shown to encode a protein containing two RNA-binding
      domains and a WW protein interaction domain. This suggests that FCA functions in
      the posttranscriptional regulation of transcripts involved in the flowering
      process. The FCA transcript is alternatively spliced with only one form encoding
      the entire FCA protein. Plants carrying the FCA gene fused to the strong
      constitutive 35S promoter flowered earlier, and the ratio and abundance of the
      different FCA transcripts were altered. Thus, FCA appears to be a component of a
      posttranscriptional cascade involved in the control of flowering time.

PMID- 9182762
TI  - Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation.
AB  - The osteoblast is the bone-forming cell. The molecular basis of osteoblast
      specific gene expression and differentiation is unknown. We previously identified
      an osteoblast-specific cis-acting element, termed OSE2, in the Osteocalcin
      promoter. We have now cloned the cDNA encoding Osf2/Cbfa1, the protein that binds
      to OSE2. Osf2/Cbfa1 expression is initiated in the mesenchymal condensations of
      the developing skeleton, is strictly restricted to cells of the osteoblast
      lineage thereafter, and is regulated by BMP7 and vitamin D3. Osf2/Cbfa1 binds to
      and regulates the expression of multiple genes expressed in osteoblasts. Finally,
      forced expression of Osf2/Cbfa1 in nonosteoblastic cells induces the expression
      of the principal osteoblast-specific genes. This study identifies Osf2/Cbfa1 as
      an osteoblast-specific transcription factor and as a regulator of osteoblast
      differentiation.

PMID- 9182763
TI  - Targeted disruption of Cbfa1 results in a complete lack of bone formation owing
      to maturational arrest of osteoblasts.
AB  - A transcription factor, Cbfa1, which belongs to the runt-domain gene family, is
      expressed restrictively in fetal development. To elucidate the function of Cbfa1,
      we generated mice with a mutated Cbfa1 locus. Mice with a homozygous mutation in
      Cbfa1 died just after birth without breathing. Examination of their skeletal
      systems showed a complete lack of ossification. Although immature osteoblasts,
      which expressed alkaline phophatase weakly but not Osteopontin and Osteocalcin,
      and a few immature osteoclasts appeared at the perichondrial region, neither
      vascular nor mesenchymal cell invasion was observed in the cartilage. Therefore,
      our data suggest that both intramembranous and endochondral ossification were
      completely blocked, owing to the maturational arrest of osteoblasts in the mutant
      mice, and demonstrate that Cbfa1 plays an essential role in osteogenesis.

PMID- 9182764
TI  - Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for
      osteoblast differentiation and bone development.
AB  - We have generated Cbfa1-deficient mice. Homozygous mutants die of respiratory
      failure shortly after birth. Analysis of their skeletons revealed an absence of
      osteoblasts and bone. Heterozygous mice showed specific skeletal abnormalities
      that are characteristic of the human heritable skeletal disorder, cleidocranial
      dysplasia (CCD). These defects are also observed in a mouse Ccd mutant for this
      disease. The Cbfa1 gene was shown to be deleted in the Ccd mutation. Analysis of
      embryonic Cbfa1 expression using a lacZ reporter gene revealed strong expression
      at sites of bone formation prior to the earliest stages of ossification. Thus,
      the Cbfa1 gene is essential for osteoblast differentiation and bone formation,
      and the Cbfa1 heterozygous mouse is a paradigm for a human skeletal disorder.

PMID- 9182766
TI  - The splicing factor BBP interacts specifically with the pre-mRNA branchpoint
      sequence UACUAAC.
AB  - The yeast splicing factor BBP (branchpoint bridging protein) interacts directly
      with pre-mRNA at or very near the highly conserved branchpoint sequence UACUAAC
      within the commitment complex. We also show that the recombinant protein
      recognizes the UACUAAC sequence. Therefore, BBP is also an acronym for
      branchpoint binding protein. The mammalian splicing factor SF1 is a BBP ortholog
      (mBBP) and an E complex component, and also has branchpoint sequence specificity.
      The relative conservation of this region in yeast and mammals correlates well
      with the RNA-binding differences between BBP and mBBP, suggesting that BBP
      contributes to branchpoint sequence definition in both systems.

PMID- 9182765
TI  - Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by
      hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short
      stature, and other changes in skeletal patterning and growth. In some families,
      the phenotype segregates with deletions resulting in heterozygous loss of CBFA1,
      a member of the runt family of transcription factors. In other families,
      insertion, deletion, and missense mutations lead to translational stop codons in
      the DNA binding domain or in the C-terminal transactivating region. In-frame
      expansion of a polyalanine stretch segregates in an affected family with
      brachydactyly and minor clinical findings of CCD. We conclude that CBFA1
      mutations cause CCD and that heterozygous loss of function is sufficient to
      produce the disorder.

PMID- 9182767
TI  - The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in
      translational control.
AB  - In Drosophila, dosage compensation occurs by increasing the transcription of the
      single male X chromosome. Four trans-acting factors encoded by the male-specific
      lethal genes are required for this process. Dosage compensation is restricted to
      males by the splicing regulator Sex-lethal, which functions to prevent the
      production of the MSL-2 protein in females by an unknown mechanism. In this
      report, we provide evidence that Sex-lethal acts synergistically through
      sequences in both the 5' and 3' untranslated regions of MSL-2 to mediate
      repression. We also provide evidence that the repression of MSL-2 is directly
      regulated by Sex-lethal at the level of translation.

PMID- 9182768
TI  - Site-specific pseudouridine formation in preribosomal RNA is guided by small
      nucleolar RNAs.
AB  - During the nucleolar maturation of eukaryotic ribosomal RNAs, many selected
      uridines are converted into pseudouridine by a thus far undefined mechanism. The
      nucleolus contains a large number of small RNAs (snoRNAs) that share two
      conserved sequence elements, box H and ACA. In this study, we demonstrate that
      site-specific pseudouridylation of rRNAs relies on short ribosomal signal
      sequences that are complementary to sequences in box H/ACA snoRNAs. Genetic
      depletion and reconstitution studies on yeast snR5 and snR36 snoRNAs demonstrate
      that box H/ACA snoRNAs function as guide RNAs in rRNA pseudouridylation. These
      results define a novel function for snoRNAs and further reinforce the idea that
      base pairing is the most common way to obtain specific substrate-"enzyme"
      interactions during rRNA maturation.

PMID- 9182769
TI  - Self-seeded fibers formed by Sup35, the protein determinant of [PSI+], a
      heritable prion-like factor of S. cerevisiae.
AB  - The [PSI+] factor of S. cerevisiae represents a new form of inheritance:
      cytosolic transmission of an altered phenotype is apparently based upon
      inheritance of an altered protein structure rather than an altered nucleic acid.
      The molecular basis of its propagation is unknown. We report that purified Sup35
      and subdomains that induce [PSI+] elements in vivo form highly ordered fibers in
      vitro. Fibers bind Congo red and are rich in beta sheet, characteristics of
      amyloids found in certain human diseases, including the prion diseases. Some
      fibers have distinct structures and these, once initiated, are self-perpetuating.
      Preformed fibers greatly accelerate fiber formation by unpolymerized protein.
      These data support a "protein-only" seeded polymerization model for the
      inheritance of [PSI+].

PMID- 9182770
TI  - Dermatoglyphics in patients with Cenani-Lenz type syndactyly: studies in a new
      case.
AB  - We describe an additional case of Cenani-Lenz syndactylism in a 4 1/2-year-old
      boy from a consanguineous Turkish family. The digital anomalies consisted partly
      of synostosis and partly of malformations of the phalanges. Although there was no
      radio-ulnar synostosis or abnormality of the bones of the feet, the findings are
      comparable to those described in the Cenani-Lenz type of syndactyly. We analysed
      the dermatoglyphics of our patient and compared them with those previously
      reported. We also investigated the relationship between the bony malformations
      and the dermatoglyphic patterns in our patient and in the literature.

PMID- 9182771
TI  - Consanguinity and common adult diseases in Israeli Arab communities.
AB  - Consanguinity has a deleterious effect with regard to congenital malformation and
      rare autosomal recessive diseases; however, little information exists on its role
      in multifactorial common adult morbidity. We investigated the effects of
      consanguinity on the prevalence of common diseases in adulthood, including
      diabetes mellitus, myocardial infarction, bronchial asthma, and duodenal ulcer.
      As part of a larger study investigating the inbreeding coefficient in the Israeli
      Arab community, we distributed questionnaires to parents of 4,100 second-grade
      students in 158 randomly chosen schools. Among the 3,772 responders (92%), 34.8%
      of the students' fathers and 31% of their mothers were found to be born to
      consanguineous matings. There was no difference in the prevalence (males,
      females) between the offspring of consanguineous versus non-consanguineous
      matings for diabetes mellitus (consanguinity: 4.3%, 1.5% vs. non-consanguinity:
      2.9%, 1.6%) myocardial infarction (2.7%, 0.03% vs. 2.3%, 0.03%), bronchial asthma
      (2.4%, 2.0% vs. 3.7%, 2.3%), or duodenal ulcer (7.0%, 3.0% vs. 7.8%, 2.9%),
      respectively. The study suggests that even in a population with a high rate of
      consanguinity, there is no significant increase in the prevalence of these common
      adult diseases.

PMID- 9182772
TI  - Expanded phenotype of cranioectodermal dysplasia (Sensenbrenner syndrome)
AB  - Cranioectodermal dysplasia (CED) is an autosomal recessive condition
      characterized by defects of ectoderm-derived structures and characteristic bone
      anomalies. We report on a 27-month-old Caucasian girl with CED, pre- and
      postnatal growth retardation, microcephaly, hypoplasia of the posterior corpus
      callosum, photophobia, and aberrant calcium homeostasis. Since new traits were
      encountered, we reviewed all reported patients and one unpublished case and
      compared the frequency rates of the individual manifestations. The findings
      present in all patients are dolichocephaly and rhizomelia. Ectodermal dysplasia
      manifestations are variable. Short thorax and heart defect are inconsistent.
      Previously unreported anomalies include growth deficiency, delayed psychomotor
      development, microcephaly, photophobia, and abnormal calcium homeostasis. These
      clinical manifestations may facilitate the diagnosis of this condition.

PMID- 9182773
TI  - Say syndrome: a new case with cystic renal dysplasia in discordant monozygotic
      twins.
AB  - Say syndrome is a rare condition characterized by cleft palate, short stature,
      and microcephaly. Abu-Libdeh et al. [1993: Am J Med Genet 45:358-360] described a
      case with cystic renal dysplasia. We describe monozygotic twins discordant for
      the syndrome with kidney dysplasia. A postzygotic mutation is proposed as the
      cause of this autosomal dominant syndrome in this case.

PMID- 9182774
TI  - Unbalanced t(4;11)(q32;q23) in a 34-year-old man with manifestations of distal
      monosomy 11q and trisomy 4q syndromes.
AB  - We present a 34-year-old man with an unbalanced translocation between the long
      arms of chromosome 4 and chromosome 11. He had manifestations of monosomy 11(q23)
      -minor facial anomalies, abnormal head shape, cryptorchidism; trisomy 4(q32)-
      hirsutism, renal disease; and manifestations attributable to both imbalances-
      heart disease, musculoskeletal anomalies, and mental retardation. FISH studies
      showed that the chromosome 11q23.3 translocation breakpoint was distal to the
      rare folate sensitive fragile site (FRA11B). The patient is the oldest reported
      with both imbalance of 4q+ and 11q-.

PMID- 9182775
TI  - Del(10)(q22.3q24.1) associated with juvenile polyposis.
AB  - Juvenile polyps are the most frequent gastrointestinal polyps with a malignant
      potential for which the genetic basis is unknown. Juvenile polyps, with a normal
      epithelium but hypertrophic lamina propria, are histologically quite distinct
      from adenomatous polyps which have dysplastic changes in epithelial nuclei.
      Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated
      somatically in adenomatous polyps and mutated in the germline of patients with
      familial adenomatous polyposis, is not linked to hereditary juvenile polyposis.
      We provide the first report indicating that a tumor suppressor gene associated
      with juvenile polyposis may be located at 10q22.3q24.1. Cytogenetic studies of a
      patient with juvenile polyposis and multiple congenital abnormalities of the
      head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10
      as the only defect, del(10)(10q22.3q24.1).

PMID- 9182776
TI  - Long-term impact of Huntington disease linkage testing.
AB  - We performed a long-term follow-up of Huntington disease (HD) predictive testing
      (an average of 6 years post-test) for 16 of 20 people who received informative
      linkage test results. Although no pre-test or baseline psychological differences
      were noted between those with an increased versus a decreased risk of HD, the
      long-term impact was dramatically different in these two groups. The low-risk
      group reported less uncertainty, anxiety or worry, fear, and worry about
      children's risk, whereas the high-risk group reported either the same or
      increased concern in these areas. Those at low risk also acknowledged an
      increased sense of control and self-esteem, whereas those at high risk reported
      decreases or no changes. One high-risk individual reported chronic depression
      that had occurred since the testing. Additionally, those at low risk reported
      greater reliance and faith in spiritual or religious beliefs than those at high
      risk. The emotional impact of HD genetic testing justifies the continued
      utilization of pre- and post-test counseling protocols. Pre-test counseling
      should include discussion of the known risks and benefits of predictive testing,
      with special emphasis on the participant's expectations for future change and
      improvement. Although the psychological impact appears mostly favorable for those
      with decreased risk, there is risk for a decline in psychological well-being over
      time for those with an increased risk for HD.

PMID- 9182777
TI  - A small deletion of 16q23.1-->16q24.2 [del(16)(q23.1q24.2).ish
      del(16)(q23.1q24.2)(D16S395+, D16S348-, P5432+)] in a boy with iris coloboma and
      minor anomalies.
AB  - We report on a 5-year-old boy with bilateral coloboma of iris, short stature,
      moderate developmental delay, and a few minor craniofacial anomalies. High
      resolution GTG banding showed a small distal deletion of one chromosome 16
      [del(16)(q23.1q24.2)]. Molecular refinement of the deletion breakpoints yielded
      that the proximal breakpoint at 16q23.1 is located between loci D16S395 (present)
      and D16S348 (absent). Comparison with previously published cases of deletion 16q
      demonstrated that the clinical phenotype is not a recognizable 16q- syndrome and
      different from the two cases of deletions of 16(q22.1 to q24.1) described by
      Callen et al. [1993]. Evidently, deletion 16(q23.1q24.2) has a milder phenotypic
      effect than other interstitial and distal 16q deletions.

PMID- 9182778
TI  - New insights into the phenotypes of 6q deletions.
AB  - Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions.
      Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia,
      speech delays, and minor anomalies. Case 2 is a male with an interstitial
      deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus
      and bilateral oligodactyly. Case 3 is a male with a terminal deletion
      [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and
      hydronephrosis. The findings in our patients and those from 57 previously
      reported cases demonstrated 3 phenotypic groups associated with 6q deletions.
      Group A [del(6)(q11-q16)] had a high incidence of hernias, upslanting palpebral
      fissures, and thin lips with lower frequency of microcephaly, micrognathia, and
      heart malformations. Group B [del(6)(q15-q25)] was associated with increased
      intrauterine growth retardation, abnormal respiration, hypertelorism, and upper
      limb malformations. Group C [del(6)(q25-qter)] was associated with retinal
      abnormalities, cleft palate, and genital hypoplasia. The only universal finding
      among all patients with 6q deletions was mental retardation. Other findings
      common to all 3 groups included ear anomalies (90%), hypotonia (82%), and
      postnatal growth retardation (68%).

PMID- 9182779
TI  - Maternal uniparental heterodisomy for chromosome 16: case report.
AB  - A patient with uniparental heterodisomy for chromosome 16 presented initially at
      prenatal diagnosis with a karyotype of 47, XX + 16 on chorionic villus sampling
      at 11 weeks gestation. The pregnancy was proceeding normally and follow up
      amniocentesis showed a normal female karyotype. At birth, the child was healthy,
      but had intrauterine growth retardation. She had unilateral talipes equinovarus
      and unilateral renal agenesis. Her growth had improved to within the normal range
      by age three years. On examination, she has epicanthic folds, a flat midface and
      almond shaped eyes. While these characteristics are not frankly abnormal, they
      are significantly different from other relatives in her family.

PMID- 9182780
TI  - Pulmonary agenesis: a predictor of ipsilateral malformations.
AB  - Pulmonary agenesis is a rare malformation that can be isolated or associated with
      other anomalies. We became interested in pulmonary agenesis after evaluation of a
      child with right pulmonary agenesis, an unlobed left lung, bilateral cleft lip
      and palate, maxillary and mandibular hypoplasia, bilateral microtia, bilateral
      radial ray hypoplasia, horseshoe kidney, and complex congenital heart disease. A
      review of the occurrence of pulmonary agenesis with other congenital anomalies
      uncovered a striking association with ipsilateral radial ray defects and/or
      hemifacial microsomia. The presence of bilateral facial or radial ray anomalies
      was indicative of bilateral pulmonary involvement. A review of the cases of
      pulmonary agenesis and associated anomalies at the Children's Hospital and
      Medical Center confirmed the association of pulmonary agenesis and ipsilateral
      involvement of face and/or radial ray. The association of pulmonary agenesis and
      ipsilateral malformations may shed light on its pathogenesis. Although the cause
      of these associated anomalies remains unclear, abnormalities in the development
      of the aortic arches during embryogenesis is an attractive hypothesis.

PMID- 9182781
TI  - Familial transmission of a deletion of chromosome 21 derived from a translocation
      between chromosome 21 and an inverted chromosome 22.
AB  - Chromosome analysis of a newborn boy with Down syndrome resulted in the
      identification of a family with an unusual derivative chromosome 22. The child
      has 46 chromosomes, including two chromosomes 21, one normal chromosome 22, and a
      derivative chromosome 22. Giemsa banding and fluorescent in situ hybridization
      (FISH) studies show that the derivative chromosome is chromosome 22 with evidence
      of both paracentric and pericentric inversions, joined to the long arm of
      chromosome 21 from 21q21.2 to qter. The rearrangement results in partial trisomy
      21 extending from 21q21.2 to 21q terminus in the patient. The child's mother,
      brother, maternal aunt, and maternal grandmother are all carriers of the
      derivative chromosome. All have 45 chromosomes, with one normal chromosome 21,
      one normal chromosome 22, and the derivative chromosome 22. The rearrangement
      results in the absence of the short arm, the centromere, and the proximal long
      arm of chromosome 21 (del 21pter-21q21.2) in carriers. Carriers of the derivative
      chromosome in this family have normal physical appearance, mild learning
      disabilities and poor social adjustment.

PMID- 9182782
TI  - "De novo" duplication Xq23-->Xq26 of paternal origin in a girl with a mildly
      affected phenotype.
AB  - We report a de novo dup(X)(q23-->q26) in a 3-year-old girl with growth
      retardation, developmental delay, and minor anomalies. X-inactivation in
      lymphocytes by BRDU labeling showed the abnormal X was late replicating. The
      androgen receptor assay (HAR) demonstrated a skewed methylation (88.8%) of the
      paternal allele and a 11.2% methylation of the maternal allele. These data, which
      suggest the duplication was paternally inherited, are the first parental-origin
      identification of a duplication Xq. The mild phenotype of the patient may be
      related to the size and region of the duplication, the low percentage of a dup(X)
      active detected by the HAR assay, or a combination of these mechanisms.

PMID- 9182783
TI  - Mosaicism for deletion 1p36.33 in a patient with obesity and hyperphagia.
AB  - We report on a 4-year-old girl with obesity and hyperphagia whose peripheral
      blood cytogenetic analysis showed mosaicism for a deletion of band 1p36.33.
      Terminal 1p deletions are rarely reported and this patient represents the first
      identified case of mosaicism. Given the subtlety of the cytogenetic abnormality
      and the possibility of mosaicism, the incidence of such deletions has probably
      been underestimated. While a characteristic phenotype associated with this
      karyotypic abnormality was described recently, the present report highlights the
      additional clinical findings of obesity and hyperphagia and the overlap of
      manifestations with Prader-Willi syndrome.

PMID- 9182784
TI  - XX-agonadism in a fetus with multiple dysraphic lesions: a new syndrome.
AB  - We report on a 19-week-old fetus with a 46,XX karyotype, normal female external
      genitalia, complete gonadal agenesis, large encephalocele, spina bifida, and
      omphalocele. We postulate a new syndrome. Hitherto no consistent malformation
      patterns have been observed in agonadism patients. True agonadism, including even
      the unusual finding of an XX gonosomal status, is obviously not as rare as
      suggested.

PMID- 9182785
TI  - Manifestations in institutionalised adults with Angelman syndrome due to
      deletion.
AB  - Undiagnosed institutionalised patients were reviewed in an attempt to identify
      those with Angelman syndrome (AS). The aim was to test these patients for
      deletion of chromosome 15(q11-13) and to describe the adult phenotype. The
      selection criteria included severe intellectual disability, ataxic or
      hypermotoric limb movements, lack of speech, a "happy" demeanour, epilepsy, and
      facial appearance consistent with the diagnosis. Patients were examined, medical
      records perused, and patients' doctors contacted as required. Genetic tests
      performed included routine cytogenetics, DNA methylation analysis (with probe
      PW71B), and fluorescence in situ hybridisation (with probes D15S10, GABRbeta3, or
      SNRPN). A deletion in the AS region was detected in 11 patients (9 males and 2
      females) of 22 tested. The mean age at last review (March 1996) was 31.5 years
      (range 24 to 36 years). Clinical assessment documented findings of large mouth
      and jaw with deep set eyes, and microcephaly in nine patients (two having a large
      head size for height). No patient was hypopigmented; 1/11 patients was fair.
      Outbursts of laughter occurred in all patients but infrequently in 7/11 (64%) and
      a constant happy demeanour was present in 5/11 (46%). All had epilepsy, with
      improvement in 5/11 (46%), no change in 4 (36%), and deterioration in 2 (18%).
      The EEG was abnormal in 10/10 patients. Ocular abnormalities were reported in 3/8
      patients (37.5%) and 4/11 (36%) had developed kyphosis. Two had never walked. All
      nine who walked were ataxic with an awkward, clumsy, heavy, and/or lilting gait.
      No patient had a single word of speech but one patient could use sign language
      for two needs (food and drink). Our data support the concept that AS resulting
      from deletion is a severe neurological syndrome in adulthood. The diagnosis in
      adults may not be straightforward as some manifestations change with age.
      Kyphosis and keratoconus are two problems of older patients.

PMID- 9182786
TI  - Pattern of malformations in the axial skeleton in human trisomy 13 fetuses.
AB  - The purpose of this study was to analyse the development of the axial skeleton in
      human trisomy 13 fetuses and to define which fields in the axial skeleton are
      affected in this condition. We investigated nine human fetuses with trisomy 13
      and gestational ages of 14-19 weeks. Whole body radiographs and radiographs of
      midsagittal tissue blocks of the cranial base and the spine were studied. In the
      youngest fetus, 14 w GA, no malformations were observed. In eight fetuses, 17-19
      weeks GA, malformations occurred in the lumbosacral spine. In four fetuses
      additional malformations were observed in the thoracic spine. The study showed
      that there was a correspondence between the extent of malformation in the
      lumbosacral spine and the thoracic spine. When mild malformation occurred in the
      lumbosacral region, no malformation was observed in the thoracic region, whereas
      malformation was observed in the thoracic region when there was extensive
      malformation in the lumbosacral region. Malformations did not occur in the
      cervical spine or the basilar part of the occipital bone, but the postsphenoidal
      part of the sphenoid bone was small and irregular in the six cases where it could
      be examined. In seven fetuses there was malformation or agenesis of the nasal
      bone. This pattern of axial skeletal malformations in trisomy 13 fetuses was not
      described previously. Comparisons are made with previous studies of the fetal
      axial skeleton in trisomy 18 and trisomy 21, where the pattern of malformations
      was different. We reiterate our recommendation that axial skeletal radiography
      should be part of the postmortem examination of fetuses with suspected or
      verified chromosome abnormalities.

PMID- 9182787
TI  - Long-term survival in typical thanatophoric dysplasia type 1.
AB  - Thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always
      lethal neonatally, although a few previous reports have documented survival up to
      4.75 years. We present a patient with survival beyond age 9 years and summarize
      his growth, development and medical history. The common Arg248Cys mutation in the
      extracellular region of fibroblast growth factor receptor 3 (FGFR3) was
      identified, eliminating the possibility that his long-term survival is
      attributable to an atypical mutation. This patient (and at least one other TD
      long-term survivor) have a rare skin disorder, acanthosis nigricans, which also
      occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any
      molecular model of the origin of acanthosis nigricans secondary to FGFR3
      mutations must account for the association of diverse mutations and these
      cutaneous effects.

PMID- 9182789
TI  - The Dutch Uniform Multicenter Registration system for genetic disorders and
      malformation syndromes.
AB  - In medical genetics, several systems are used to classify and code genetic
      disorders for the purpose of automated registration. In the Netherlands, a
      genetic diagnosis code system has been developed that links a unique four-digit
      code to a principal description and all current synonyms. The main goal of this
      coding system is to enable nationwide uniformity of coding, without losing access
      to information stored in the past, identified by the ICD/BPA code (the
      International Classification of Diseases as adapted by the British Paediatric
      Association) and/or the MIM code (McKusick's classification in Mendelian
      Inheritance in Man). To this effect, the Dutch diagnosis code is cross-referenced
      with the 2 pre-existing classification systems. Developments in medical genetics
      make regular updates of all coding systems necessary. In the Netherlands, new
      diagnosis codes are assigned centrally to preserve uniformity and distributed
      periodically to all 8 clinical genetic centers. Diagnosis codes are assigned in
      numerical order of inclusion, enabling quick and easy updates. It is possible to
      include subclassifications of disorders according to pattern of inheritance, gene
      location, and gene mutations and to cover all disorders and disorder subtypes
      which are not clearly distinguished by the 2 pre-existing classification systems.
      The architecture of the coding system is suitable for international use. It
      offers a practical solution for clinical geneticists in need of a coding system
      suitable for clinical use. The use of the diagnosis code will also facilitate
      reliable comparison of data and nationwide genetic epidemiological studies.

PMID- 9182788
TI  - Two new mild homozygous mutations in Gaucher disease patients: clinical signs and
      biochemical analyses.
AB  - Gaucher disease (GD) is a lysosomal storage disorder resulting from impaired
      activity of lysosomal beta-glucocerebrosidase. More than 60 mutations have been
      described in the GBA gene. They have been classified as lethal, severe, and mild
      on the basis of the corresponding phenotype. The fact that most GD patients are
      compound heterozygous and that most type 1 patients bear the N370S allele, which
      by itself causes a mild phenotype, make it difficult to correlate the clinical
      signs with the mutations. Besides N370S, about 10 mild mutations have been
      described, but only one undoubtedly classified as mild was found at homozygosity.
      Here we report 2 novel mutations, I402T and V375L, at homozygosity in 2 adult
      Italian type 1 GD patients. Some properties of the I402T fibroblast enzyme have
      been compared to those of the enzyme from cells of several N370S/N370S patients.
      Analysis of the catalytic properties and heat stability as well as the response
      to phosphatidylserine and sphingolipid activator protein indicate a marked
      similarity between the 2 enzymes. The finding of another, unrelated patient
      bearing the I402T mutation (in this case as a compound heterozygote with mutation
      N370S) suggests that this allele might be quite frequent in the area of Sicily
      from where both patients originated. In conclusion, the phenotypic expression in
      the 2 homozygous patients presented here and the biochemical data for one of them
      allowed the classification of these mutations as mild thus extending the group of
      mild mutations found at homozygosity.

PMID- 9182790
TI  - Detection of CAG repeats using silver staining in patients with Huntington
      disease in Hungary.

PMID- 9182791
TI  - Shprintzen-Goldberg syndrome with osteopenia and progressive hydrocephalus.

PMID- 9182793
TI  - How does a vesicle know it is full?

PMID- 9182792
TI  - Not a new Seckel-like syndrome but ear-patella-short stature syndrome.

PMID- 9182794
TI  - Presenilins: genes for life and death.

PMID- 9182796
TI  - Vertebrate neural induction: inducers, inhibitors, and a new synthesis.

PMID- 9182795
TI  - (S)NO signals: translocation, regulation, and a consensus motif.

PMID- 9182797
TI  - The vibrator mutation causes neurodegeneration via reduced expression of PITP
      alpha: positional complementation cloning and extragenic suppression.
AB  - The mouse vibrator mutation causes an early-onset progressive action tremor,
      degeneration of brain stem and spinal cord neurons, and juvenile death. We cloned
      the vibrator mutation using an in vivo positional complementation approach and
      complete resequencing of the resulting 76 kb critical region from vibrator and
      its parental chromosome. The mutation is an intracisternal A particle retroposon
      insertion in intron 4 of the phosphatidylinositol transfer protein alpha gene,
      causing a 5-fold reduction in RNA and protein levels. Expression of neurofilament
      light chain is also reduced in vibrator, suggesting one signaling pathway that
      may underlie vibrator pathology. The vibrator phenotype is suppressed in one
      intercross. We performed a complete genome scan and mapped a major suppressor
      locus (Mvb-1) to proximal chromosome 19.

PMID- 9182799
TI  - Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb
      visualized by optical imaging.
AB  - Odors are thought to be represented by a distributed code across the glomerular
      modules in the olfactory bulb (OB). Here, we optically imaged presynaptic
      activity in glomerular modules of the zebrafish OB induced by a class of natural
      odorants (amino acids [AAs]) after labeling of primary afferents with a calcium
      sensitive dye. AAs induce complex combinatorial patterns of active glomerular
      modules that are unique for different stimuli and concentrations. Quantitative
      analysis shows that defined molecular features of stimuli are correlated with
      activity in spatially confined groups of glomerular modules. These results
      provide direct evidence that identity and concentration of odorants are encoded
      by glomerular activity patterns and reveal a coarse chemotopic organization of
      the array of glomerular modules.

PMID- 9182798
TI  - Control of dopamine release in the retina: a transgenic approach to neural
      networks.
AB  - Dopaminergic, interplexiform amacrines (DA cells) were labeled in transgenic mice
      with human placental alkaline phosphatase, an enzyme that resides on the outer
      surface of the cell membrane. It was therefore possible to investigate their
      activity in vitro after dissociation of the retina with whole-cell current and
      voltage clamp, as well as their connections in the intact retina with the
      electron microscope. DA cells generate action potentials even in the absence of
      synaptic inputs. This activity is abolished by the amacrine cell transmitters
      GABA and glycine, which induce an inward current carried by chloride ions, and is
      stimulated by kainate, an agonist at the receptor for the bipolar cell
      transmitter glutamate, which opens nonselective cation channels. Since DA cells
      are postsynaptic to amacrine and bipolar cells, we suggest that the spontaneous
      discharge of DA cells is inhibited in the dark by GABAergic amacrines that
      receive their input from off-bipolars. Upon illumination, the GABA-inhibition is
      removed, DA cells generate action potentials, and their firing is modulated by
      the excitation received from on-bipolars.

PMID- 9182800
TI  - Single neuron activity in human hippocampus and amygdala during recognition of
      faces and objects.
AB  - The hippocampus and its associated structures play a key role in human memory,
      yet the underlying neuronal mechanisms remain unknown. Here, we report that
      during encoding and recognition, single neurons in the medial temporal lobe
      discriminated faces from inanimate objects. Some units responded selectively to
      specific emotional expressions or to conjunctions of facial expression and
      gender. Such units were especially prevalent during recognition, and the
      responses depended on stimulus novelty or familiarity. Traces of exposure to
      faces or objects were found a few seconds after stimulus removal as well as 10 hr
      later. Some neurons maintained a record of previous stimulus presentation that
      was more accurate than the person's conscious recollection. We propose that the
      human medial temporal lobe constructs a "cognitive map" of stimulus attributes
      comparable to the map of the spatial environment described in the rodent
      hippocampus.

PMID- 9182801
TI  - Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic
      growth.
AB  - Neurons within each layer of cerebral cortex express multiple members of the
      neurotrophin family and their corresponding receptors. This multiplicity could
      provide functional redundancy; alternatively, different neurotrophins may direct
      distinct aspects of cortical neuronal growth and differentiation. By neutralizing
      endogenous neurotrophins in organotypic slices of developing cortex with Trk
      receptor bodies (Trk-IgGs), we found that BDNF and NT-3 oppose one another in
      regulating the dendritic growth of pyramidal neurons. In layer 4, both endogenous
      and exogenous NT-3 inhibited the dendritic growth stimulated by BDNF. In
      contrast, in layer 6 both endogenous and exogenous BDNF inhibited dendritic
      growth stimulated by NT-3. These antagonistic actions of endogenous BDNF and NT-3
      provide a mechanism by which dendritic growth and retraction can be dynamically
      regulated during cortical development, and suggest that the multiple
      neurotrophins expressed in developing cortex represent distinct components of an
      extracellular signaling system for regulating dendritic growth.

PMID- 9182802
TI  - Direct evidence for homotypic, glia-independent neuronal migration.
AB  - Neuronal precursors born in the subventricular zone (SVZ) of the neonatal and
      adult rodent brain migrate 3-8 mm from the walls of the lateral ventricle into
      the olfactory bulb. This tangentially oriented migration occurs without the
      guidance of radial glia or axonal processes. The cells move closely associated,
      forming elongated aggregates called chains, which are ensheathed by astrocytes.
      We have developed a culture system in which postnatal mouse SVZ neuronal
      precursors assemble into chains with ultrastructural and immunocytochemical
      characteristics equivalent to those in vivo but without the astrocytic sheath.
      Time-lapse videomicrography revealed that individual cells migrate along the
      chains very rapidly (approximately 122 microm/hr) in both directions. Periods of
      cell body translocation were interspersed with stationary periods. This saltatory
      behavior was similar to radial glia-guided migration but approximately 4 times
      faster. Neuronal precursors isolated from embryonic cortical ventricular zone or
      cerebellar external granule layer did not form chains under these conditions,
      suggesting that chain migration is characteristic of SVZ precursors. This study
      directly demonstrates that SVZ neuronal precursors migrate along each other
      without the assistance of astrocytes or other cell types. (Additional data are
      presented in www.cell.com).

PMID- 9182803
TI  - TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret.
AB  - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a
      family of TGF-beta-related neurotrophic factors (TRNs), which have trophic
      influences on a variety of neuronal populations. A receptor complex comprised of
      TrnR1 (GDNFR alpha) and Ret was recently identified and found to be capable of
      mediating both GDNF and NTN signaling. We have identified a novel receptor based
      on homology to TrnR1, called TrnR2, that is 48% identical to TrnR1, and is
      located on the short arm of chromosome 8. TrnR2 is attached to the cell surface
      via a GPI-linkage, and can mediate both NTN and GDNF signaling through Ret in
      vitro. Fibroblasts expressing TrnR2 and Ret are approximately 30-fold more
      sensitive to NTN than to GDNF treatment, whereas those expressing TrnR1 and Ret
      respond equivalently to both factors, suggesting the TrnR2-Ret complex acts
      preferentially as a receptor for NTN. TrnR2 and Ret are expressed in neurons of
      the superior cervical and dorsal root ganglia, and in the adult brain.
      Comparative analysis of TrnR1, TrnR2, and Ret expression indicates that multiple
      receptor complexes, capable of mediating GDNF and NTN signaling, exist in vivo.

PMID- 9182804
TI  - Disulfide-linked head-to-head multimerization in the mechanism of ion channel
      clustering by PSD-95.
AB  - The PSD-95/SAP90 family of PDZ-containing proteins is directly involved in the
      clustering of specific ion channels at synapses. We report that channel
      clustering depends on a conserved N-terminal domain of PSD-95 that mediates
      multimerization and disulfide linkage of PSD-95 protomers. This N-terminal
      multimerization domain confers channel clustering activity on a single PDZ
      domain. Thus, channel clustering depends on aggregation of PDZ domains achieved
      by head-to-head multimerization of PSD-95, rather than by concatenation of PDZ
      domains in PSD-95 monomers. This mechanism predicts that PSD-95 can organize
      heterogeneous membrane protein clusters via differential binding specificities of
      its three PDZ domains. PSD-95 and its relative chapsyn-110 exist as disulfide
      linked complexes in rat brain, consistent with head-to-head multimerization of
      these proteins in vivo.

PMID- 9182805
TI  - Expression of a putative vesicular acetylcholine transporter facilitates quantal
      transmitter packaging.
AB  - A putative vesicular acetylcholine transporter (VAChT) was overexpressed in
      developing Xenopus spinal neurons by injection of rat VAChT cDNA or synthetic
      mRNA into Xenopus embryos. This resulted in a marked increase in the amplitude
      and frequency of miniature excitatory postsynaptic currents at neuromuscular
      synapses, reflecting an over 10-fold increase in the vesicular packaging of
      acetylcholine (ACh). The effect appeared in developing neurons even before
      synaptogenesis and was blocked by L-vesamicol, a specific blocker of ACh uptake
      into synaptic vesicles. Mutational studies showed that two highly conserved
      aspartate residues within putative transmembrane domains 4 and 10 are essential
      for the transport activity. These results provide direct evidence for the
      physiological function of a putative VAChT and demonstrate that quantal size can
      be regulated by changes in vesicular transporter activity.

PMID- 9182806
TI  - Association and stoichiometry of K(ATP) channel subunits.
AB  - ATP-sensitive potassium channels (K(ATP) channels) are heteromultimers of
      sulfonylurea receptors (SUR) and inwardly rectifying potassium channel subunits
      (K(IR)6.x) with a (SUR-K(IR)6.x)4 stoichiometry. Association is specific for
      K(IR)6.x and affects receptor glycosylation and cophotolabeling of K(IR)6.x by
      125I-azidoglibenclamide. Association produces digitonin stable complexes with an
      estimated mass of 950 kDa. These complexes can be purified by lectin
      chromatography or by using Ni2(+)-agarose and a his-tagged SUR1. Expression of
      SUR1 approximately (K(IR)6.2)i fusion constructs shows that a 1:1 SUR1:K(IR)6.2
      stoichiometry is both necessary and sufficient for assembly of active K(ATP)
      channels. Coexpression of a mixture of strongly and weakly rectifying triple
      fusion proteins, rescued by SUR1, produced the three channel types expected of a
      tetrameric pore.

PMID- 9182807
TI  - Agouti signaling protein inhibits melanogenesis and the response of human
      melanocytes to alpha-melanotropin.
AB  - In mouse follicular melanocytes, the switch between eumelanin and pheomelanin
      synthesis is regulated by the extension locus, which encodes the melanocortin-1
      receptor (MC1R) and the agouti locus, which encodes a novel paracrine-signaling
      molecule that inhibits binding of melanocortins to the MC1R. Human melanocytes
      express the MC1R and respond to melanotropins with increased proliferation and
      eumelanogenesis, but a potential role for the human homolog of agouti-signaling
      protein, ASIP, in human pigmentation has not been investigated. Here we report
      that ASIP blocked the binding of alpha-melanocyte-stimulating hormone (alpha-MSH)
      to the MC1R and inhibited the effects of alpha-MSH on human melanocytes.
      Treatment of human melanocytes with 1 nM-10 nM recombinant mouse or human ASIP
      blocked the stimulatory effects of alpha-MSH on cAMP accumulation, tyrosinase
      activity, and cell proliferation. In the absence of exogenous alpha-MSH, ASIP
      inhibited basal levels of tyrosinase activity and cell proliferation and reduced
      the level of immunoreactive tyrosinase-related protein-1 (TRP-1) without
      significantly altering the level of immunoreactive tyrosinase. In addition, ASIP
      blocked the stimulatory effects of forskolin or dibutyryl cAMP, agents that act
      downstream from the MC1R, on tyrosinase activity and cell proliferation. These
      results demonstrate that the functional relationship between the agouti and MC1R
      gene products is similar in mice and humans and suggest a potential physiologic
      role for ASIP in regulation of human pigmentation.

PMID- 9182808
TI  - Cloning of human keratolinin cDNA: keratolinin is identical with a cysteine
      proteinase inhibitor, cystatin A, and is regulated by Ca2+, TPA, and cAMP.
AB  - Keratolinin has been described as one of the precursor proteins of cornified cell
      envelope of keratinocytes. Using rabbit polyclonal anti-human keratolinin
      antibody, we isolated a cDNA clone of human keratolinin gene from a human Agt11
      cDNA expression library that was constructed by random priming from poly(A)+RNA
      extracted from cultured normal human keratinocytes. Screening by rabbit anti
      human keratolinin antibody detected one positive clone (HKL-1). The recombinant
      12.5-kDa protein constructed from the clone reacted specifically with the anti
      human keratolinin antibody. DNA sequence analysis revealed that HKL-1 clone was
      448 bp long, and its putative amino acid sequence was identical with that of a
      human cysteine proteinase inhibitor, cystatin A. Western blot analysis showed
      that the commercially available recombinant cystatin A also reacted specifically
      with the anti-human keratolinin antibody. Northern blot analysis indicated that
      HKL-1 clone hybridizes with mRNA of about 0.5 kb, consistent with the size of the
      HKL-1 clone. The keratolinin mRNA was highly expressed in cultured human
      keratinocytes in high Ca2+ (1 mM); in low Ca2+ (0.05 mM), the keratolinin mRNA
      expression was significantly lower. Using SV40-transformed human keratinocytes
      (SVHK cells), we further analyzed the regulation of keratolinin mRNA. In low Ca2+
      (0.05 mM), keratolinin mRNA in SVHK cells was marginally detectable. Upon shift
      to 1 mM calcium, keratolinin mRNA was markedly increased. The upregulation of
      keratolinin mRNA was also observed by the treatment of SVHK cells with 10 ng TPA
      per ml or 100 microM forskolin under low calcium conditions (0.05 mM). Our
      results indicate that keratolinin is identical with cystatin A, a cysteine
      proteinase inhibitor, and its expression is positively regulated by Ca2+, TPA,
      and forskolin.

PMID- 9182809
TI  - Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of
      cicatricial pemphigoid.
AB  - We characterized basement membrane zone (BMZ) autoantigens targeted by
      autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a
      patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The
      AAb labeled a lower BMZ component on salt-split skin and localized to the lower
      lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (IEM)
      but did not label blood vessels. The AAb did not react with EHS laminin-1 and
      type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1
      domain of type VII collagen by dot blotting and western blotting. We focused our
      studies on the laminin family, as laminin-5 was identified as an autoantigen in
      cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes
      (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6
      but not laminin-5) were studied by western blotting. Under nonreducing
      conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely
      and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even
      though abundant laminin-5 was present. InJEB keratinocyte medium, however, the
      600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb
      also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this
      patient and two other patients with anti-laminin-5 cicatricial pemphigoid
      immunoprecipitated both laminin-6 and laminin-5. Taken together, the results of
      IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ
      immunolabeling indicate that laminin-6, as well as laminin-5, is identified by
      the AAb from a subset of cicatricial pemphigoid patients. We propose the name
      "anti-laminin cicatricial pemphigoid" for this subset.

PMID- 9182810
TI  - Linear IgA bullous dermatosis with IgA antibodies exclusively directed against
      the 180- or 230-kDa epidermal antigens.
AB  - This study describes the presence in sera from patients with linear IgA bullous
      dermatosis (LABD) of IgA antibodies specific for 230- or 180-kDa epidermal
      antigens. Of 11 patients' sera with IgA antibodies reactive with the epidermal
      antigens obtained from cultured keratinocytes, 6 sera recognized the 230-kDa
      antigen and co-migrated with the polypeptide recognized by a human monoclonal
      antibody against the 230-kDa bullous pemphigoid antigen (BPAgl). Five sera
      recognized the 180-kDa antigen and co-migrated with the polypeptide stained by a
      polyclonal antibody to the 180-kDa bullous pemphigoid antigen (BPAg2). None of
      these LABD sera contained IgG antibodies reactive with the basement membrane zone
      antigens and none labeled a 97-kDa epidermal antigen or a 290-kDa dermal antigen.
      Immunoaffinity-purified IgA antibodies from the 230 kDa band further reacted with
      the epidermal side of the skin basement membrane zone. Epitope mapping with
      rBP55, a fusion protein containing the C-terminal end of BPAg1, suggested that
      the major antigenic epitopes for LABD and BP antibodies on the 230-kDa antigen
      are different. Only one serum with IgA antibodies was found to label rBP55,
      contrasting with nine of ten BP sera reacting with this protein. Our study
      demonstrates the presence of an exclusive IgA response against the 230- or 180
      kDa antigens in a subset of patients with LABD.

PMID- 9182811
TI  - Immunologic protection afforded by sunscreens in vitro.
AB  - Several studies have suggested a lack of correlation between sunscreen sun
      protection factor and protection of the skin immune system, potentially allowing
      greater damage to the skin by removing the natural protective erythemal response
      to sun exposure. Despite this, routine testing of immune protection afforded by
      sunscreens is not performed by industry. Current laboratory methods for
      investigating the efficacy of sunscreen protection of epidermal immune function
      use the induction of contact hypersensitivity or epidermal cell alloantigen
      presentation. Animal models, cell culture systems, and in vivo human studies are
      commonly employed, but all these systems have significant drawbacks for use in
      routine testing. The purpose of this study was to develop an in vitro system for
      testing the immunologic protection afforded by sunscreens in human skin. Five
      test sunscreens plus a vehicle control were tested in a "blind" fashion for their
      in vitro level of immune protection. Creams were applied in a standard manner to
      human whole skin explants and were irradiated over a range of physiologic doses
      using an Oriel solar simulator. A mixed epidermal lymphocyte reaction was used to
      quantify epidermal alloantigen-presenting capacity, in the presence or absence of
      test cream, for five explants. Results consistently demonstrated that all the
      test sunscreens protected beyond their designated sun protection factors, whereas
      the vehicle conferred no protection. The explant-mixed epidermal lymphocyte
      reaction system gave consistent, reproducible results and may prove useful for
      the allocation of an immune protection factor to all sunscreens.

PMID- 9182812
TI  - Keratinocyte K+ channels mediate Ca2+-induced differentiation.
AB  - K+ channel activation has been associated with growth or differentiation in many
      cells. We have previously identified a 70-pS K+ channel that was found only in
      differentiated involucrin-positive cells. In this study we examined the role of
      K+ channels in Ca2+-induced keratinocyte differentiation. Consistent with our
      previous report, we found that a K+ conductance developed only in cells cultured
      in high extracellular Ca2+. Addition of charybdotoxin or verapamil blocked these
      K+ channels and inhibited Ca2+-induced differentiation, as assessed by cornified
      envelope formation or transglutaminase activity. These results suggest that K+
      channel activation is necessary for Ca2+-induced differentiation. Finally, we
      used (125)I-labeled charybdotoxin to demonstrate the presence of K+ channels in
      intact human and mouse epidermis, hair follicles, and eccrine glands, indicating
      that these channels are found in keratinocytes both in vitro and in vivo. Thus K+
      channels may moderate Ca2+ influx in more differentiated keratinocytes and may
      play a central role in keratinocyte differentiation.

PMID- 9182813
TI  - Epidermal steroid sulfatase and cholesterol sulfotransferase are regulated during
      late gestation in the fetal rat.
AB  - Lipids in the stratum corneum (SC) are organized into lamellar membrane unit
      structures that provide the permeability barrier. Cholesterol sulfate, a SC
      membrane lipid, is synthesized by cholesterol sulfotransferase (CSTase) in the
      lower epidermis and hydrolyzed to cholesterol by steroid sulfatase (SSase) in the
      SC. To determine whether these enzymes are induced during barrier ontogenesis, we
      examined their activity in epidermis of fetal rats before (gestational day 17),
      during (day 19), and after (day 21) barrier formation. CSTase activity increased
      approximately 10-fold between day 17 and day 19, then declined between day 19 and
      day 21. In contrast, SSase activity reached its peak activity on day 21,
      increasing >5-fold. Fetal rat skin explants develop a SC and barrier over the
      same time course in vitro as in utero. Likewise, CSTase and SSase activities
      during in vitro ontogenesis precisely mirrored those obtained in utero. Moreover,
      hormones that accelerate barrier ontogenesis (e.g. glucocorticoids, thyroid
      hormone, and estrogen) accelerated the increase in CSTase and SSase activities
      during in vitro ontogenesis. mRNA levels of SSase increased in parallel with
      enzymatic activity, suggesting that these developmental changes are regulated at
      the genomic level. Finally, addition of exogenous cholesterol sulfate to explants
      in vitro did not accelerate either SC development or barrier formation. These
      studies suggest that induction of the cholesterol sulfate cycle enzymes during SC
      ontogenesis is a component of the fetal epidermal differentiation program and
      that the synthetic and degradative enzymes of this pathway are differentially
      regulated.

PMID- 9182814
TI  - Evidence that beta1 integrins in keratinocyte cell-cell junctions are not in the
      ligand-occupied conformation.
AB  - Integrins are a family of heterodimeric cell surface molecules that function as
      adhesion receptors in cell-cell and cell-extracellular matrix contact. Integrins
      of the beta1 family are found on keratinocytes clustered at sites of cell-cell
      junctions both in culture and in normal skin. The possibility that these
      integrins function in cell-cell adhesion has been both supported and refuted in
      recent conflicting publications. Rather than testing further for the presence or
      absence of an interaction, we present evidence to show that beta1 integrins in
      keratinocyte cell-cell junctions are in the non-ligand-occupied conformation. We
      transfected keratinocytes with a construct that expresses a chimeric cell surface
      molecule containing the integrin beta1 cytoplasmic tail. This chimera is thought
      to mimic the ligand-occupied receptor and has previously been shown to be
      actively localized to focal adhesions in fibroblasts. We find that keratinocytes
      are also able to localize this chimera in focal adhesions but do not localize it
      to areas of cell-cell junctions. A monoclonal anti-beta1 antibody that has been
      previously shown to preferentially recognize ligand-occupied beta1 receptors was
      used to stain keratinocytes. This antibody showed staining of focal adhesions,
      with little or no staining of cell-cell junctions. In contrast, four other anti
      beta1 antibodies showed strong, preferential staining at cell-celljunctions.
      Double staining confirmed that both the conformation-specific monoclonal antibody
      and a pan-beta1 antibody were capable of recognizing the same focal adhesions.
      Taken together, these data indicate that integrins in cell- cell junctions of
      keratinocytes are in the non-ligand-occupied conformation. Although we do not
      directly prove the absence of an integrin-integrin interaction at this site, we
      show that any such interaction does not induce the ligand-occupied conformation
      and, therefore, is less likely to play a major role in cytoskeletal re
      organization or signal transduction.

PMID- 9182815
TI  - Neonatal lupus erythematosus: HLA-DR and -DQ distributions are different among
      the groups of anti-Ro/SSA-positive mothers with different neonatal outcomes.
AB  - Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder of infants
      characterized by two major clinical manifestations; cutaneous lupus lesions and
      congenital heart block (CHB). The disease is associated with placentally
      transferred maternal anti-Ro/SSA and/or La/SSB antibodies. There is a tendency
      for the same disease expression to occur within a sibship. To reveal a possible
      association of class II MHC genes with maternal anti-Ro/SSA autoimmune responses
      and neonatal outcomes in NLE with a relatively homogeneous ethnic background,
      haplotype, and allele distributions were analyzed based on the PCR-RFLP results
      in 26 Japanese anti-Ro/SSA-positive mothers from three groups defined by neonatal
      outcomes. The results were as follows: (i) maternal HLA-DR5 haplotype DRB1*1101
      DQA1*0501-DQB1*0301 and individual class II alleles making up this haplotype were
      significantly associated with neonatal cutaneous lupus but not CHB. Conversely,
      maternal HLA-DQB1*0602 carried on HLA-DR2 haplotypes was associated with CHB but
      not cutaneous NLE; (ii) HLA-DQA1 alleles with glutamine at position 34 of the
      first domain, which have reportedly been associated with the autoimmune responses
      to Ro/SSA antigens in other ethnic groups, were increased in the mothers of
      infants with cutaneous involvement; and (iii) there was no particular class II
      HLA profile that distinguished the disease manifestations in infants. These
      findings suggest that specific maternal MHC class II genes might correlate with
      specific neonatal outcomes in NLE.

PMID- 9182816
TI  - Differential stimulation of ERK and JNK activities by ultraviolet B irradiation
      and epidermal growth factor in human keratinocytes.
AB  - Exposure of mammalian cells to solar ultraviolet (UV) radiation leads to the
      expression of several genes, and UV has been recognized as a major initiator and
      promoter of skin cancer. The component of the solar radiation that contributes
      most to human skin malignancy is UVB (280-320 nm) and, to a lesser extent, UVA
      (320-400 nm), whereas the high-energy UVC (100-280 nm) is absorbed by the earth's
      upper atmosphere. Sublethal doses of UVB produce strong induction of c-jun and c
      fos transcripts in several cells including human primary keratinocytes. The
      present report confirms that this is also the case in the HaCaT cell line and
      shows that similar UVB doses are potent inducers of the JNK/SAPK family of
      mitogen-activated protein kinases but only weak activators of ERKs. Epidermal
      growth factor (EGF) caused rapid induction of both JNK- and ERK-signaling
      pathways, and the downmodulation of the EGF-signaling pathway by EGF pre
      treatment inhibited the UVB-induced JNK1 activation. Prior UVB irradiation of the
      cells decreased the level of the ERK2 activation by a subsequent EGF treatment,
      but this sensitized the cells and allowed for the super-activation of JNK1 after
      a rechallenge with either UVB or EGF. The antioxidant N-acetylcysteine impaired
      the UVB- and EGF-induced activation of JNK1. Our data suggest the presence of
      shared signaling component(s) in the UVB- and EGF-induced cellular response
      pathways and imply that oxidative stress plays a significant role in the
      activation of JNK1 by UVB and EGF.

PMID- 9182817
TI  - Induction of tumor necrosis factor-alpha in vivo by a skin irritant, tributyltin,
      through activation of transcription factors: its pharmacological modulation by
      anti-inflammatory drugs.
AB  - Skin irritant reactions are under the control of a network of cytokines and lipid
      mediators. This study characterized the production of tumor necrosis factor-alpha
      (TNF) induced by a skin irritant treatment, tributyltin (TBT), in mice through
      transcription factor activation and its pharmacologic modulation by anti
      inflammatory agents. The ears of BALB/c mice were painted with different amounts
      of TBT (67-536 nmol in acetone) or with acetone alone. At different times
      thereafter, TNF production was analyzed both at the mRNA and protein level, by
      semiquantitative RT-PCR and L929 cytotoxicity assay, respectively. TBT induced
      rapid (1 h) TNF gene expression and protein synthesis. Maximal TNF production was
      observed 2 h after treatment. The production of TNF was paralleled by
      accumulation of skin water; this was partially prevented by intraperitoneal
      injection of antibody against murine TNF. These data indicate that skin
      irritation induced by TBT is attributable, in addition to the actions of other
      inflammatory mediators, to the action of keratinocyte-derived TNF. TNF production
      was preceded by a rapid (5 min) activation of nuclear factor-kappaB (NF-kappaB),
      which was also maximal 30 min after treatment. TBT-induced accumulation of skin
      water and TNF production were significantly reduced by topical treatment with
      dexamethasone and pentamidine, two anti-inflammatory agents. Interestingly,
      dexamethasone, but not pentamidine, decreased TBT-induced NF-kappaB activation,
      confirming in vivo that the glucocorticoid receptor interacts functionally within
      the nucleus with other transcription factors opposing one another's activity.

PMID- 9182818
TI  - Noncutaneous malignant tumors in the PUVA follow-up study: 1975-1996.
AB  - There is concern about possible association between PUVA treatment and an
      increased risk of noncutaneous cancer. An alteration in the risk of cancer among
      persons with psoriasis has also been postulated. To test this hypothesis, for
      nearly two decades we have prospectively followed 1380 patients who first began
      PUVA treatment for psoriasis in 1975-1976. We compare the risk of noncutaneous
      cancer in our cohort with that expected based on general population incidence
      rates. The overall risk of noncutaneous cancer was nearly identical to that
      expected in general population. For three separate sites, we noted significant
      increases: thyroid cancer (RR = 3.57, 95% CI = 1.16-8.34), breast cancer (RR =
      1.81, 95% CI = 1.19-2.64), and central nervous system neoplasms (RR = 2.80, 95%
      CI = 1.13-5.57). Since 1987, however, the risk of central nervous system
      neoplasms has not been elevated (RR = 0.00, 95% CI = 0.00-3.35) and the relative
      risk of breast cancer was lower than in the prior decade and not statistically
      significant. There was no association between higher levels of exposure to PUVA
      and the risk of any of these cancers. We did not detect any significant increase
      in the risk of lymphoma or leukemia. Our study does not support the hypothesis
      that long-term PUVA treatment increases the risk of noncutaneous cancer.

PMID- 9182819
TI  - Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with
      ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180
      spans the lamina lucida.
AB  - The BP180 antigen is a hemidesmosomal glycoprotein that is recognized by
      autoantibodies associated with three autoimmune disorders, bullous pemphigoid
      (BP), herpes gestationis (HG), and cicatricial pemphigoid (CP). BP and HG sera
      have been shown to recognize a common extracellular site located near the
      membrane-spanning domain of this protein, whereas CP sera react predominantly
      with a distinct site near the C terminus. In the current study, the main
      immunogenic sites on the BP180 ectodomain were ultrastructurally localized using
      six BP sera, four CP sera, and two rabbit antisera. The immunolocalization
      pattern of BP sera was largely restricted to the upper lamina lucida region
      immediately subjacent to the epidermal hemidesmosome and closely resembled that
      of a rabbit antiserum directed against the NC16A (membrane-proximal) domain of
      BP180. CP sera, on the other hand, exhibited a lower lamina lucida/lamina densa
      labeling pattern that was strikingly similar to that of rabbit antibodies to the
      BP180 C-terminal region. Finally, antibodies to the BP180 C-terminal region co
      localized with an anti-laminin-5 antibody in the anchoring filament zone. These
      findings strongly suggest that the BP180 extracellular domain exists in an
      extended conformation, with the C terminus of this protein projecting into the
      lamina densa. These data support the hypothesis that BP180 contributes to the
      structure and function of the anchoring filaments. Differences in the
      ultrastructural mapping of BP and CP autoantibodies appear to correlate with
      epitope mapping data, which, together, may help to explain the clinical
      heterogeneity observed in this group of bullous disorders.

PMID- 9182820
TI  - Identification of novel cadherins expressed in human melanoma cells.
AB  - Cadherin molecules are essential for tissue morphogenesis and are also related to
      cancer invasion and metastasis. Although normal melanocytes express E- and P
      cadherin, the activity and expression of E- and P-cadherin in melanoma cells are
      still unknown. We measured the homophilic adhesion activity of human normal
      epidermal melanocytes and the melanoma cell lines MeWo and A375. The melanoma
      cells showed stronger homophilic adhesion activity than did the melanocytes,
      despite the lower expression of E- and P-cadherin in the melanoma cells. This
      result suggested that melanoma cells expressed other types of homophilic adhesion
      molecules. Using degenerate primers to amplify multiple cadherin subtypes, we
      performed a polymerase chain reaction (PCR) with the first strand of cDNAs
      generated by reverse transcription of the mRNAs of the melanoma cells, and we
      isolated two known cadherin fragments, N-cadherin and PC42, and six novel
      cadherin fragments, cadherins ME1-ME6. The reverse transcriptase-PCR using
      specific primers of cadherins including E-, P-, and N-cadherins, PC42, and
      cadherins ME1-ME6 revealed that the melanoma cells expressed more kinds of
      cadherin molecules than did the melanocytes. Such cadherins may play an important
      role in melanoma cell-cell adhesion.

PMID- 9182821
TI  - T helper 1 cytokine mRNA is increased in spontaneously regressing primary
      melanomas.
AB  - Spontaneous tumor regression, which is observed clinically and histologically in
      some primary melanomas, occurs in the absence of any effective therapy. It is
      probably immunologically mediated, because regressing melanomas are infiltrated
      with larger numbers of activated T cells, primarily CD4+, than nonregressing
      melanomas. To investigate the hypothesis that spontaneous regression of melanomas
      is caused by T-cell cytokine production, cytokine mRNA expression in 20 primary
      melanomas was examined using a noncompetitive, quantitative reverse-transcriptase
      polymerase chain reaction method. DNA standards were used to generate known
      numbers of molecules in each sample. Results were standardized to the internal
      control, glyceraldehyde-3-phosphate dehydrogenase. mRNA for CD35, lymphotoxin
      (TNF-beta), and IL-2 were significantly elevated in the ten regressing melanomas
      compared to the ten nonregressing melanomas. IFN-gamma mRNA was also elevated in
      regressing melanomas but failed to reach statistical significance. The Th2
      cytokines IL-10 and IL-13 did not show differences in the regressing melanomas
      compared to nonregressing melanomas; neither did the pro-inflammatory cytokines
      IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha, nor the growth factors, bFGF and
      TGF-beta or GM-CSF. This study shows an association between Th1 cytokines and
      spontaneously regressing melanomas. Although we have not shown that these
      cytokines cause regression, these findings support our hypothesis that activated
      CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines.

PMID- 9182822
TI  - No evidence of KSHV/HHV-8 in mycosis fungoides or associated disorders.
AB  - The recently discovered human virus known as Kaposi's sarcoma-associated
      herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) has been associated with body
      cavity-based lymphomas in AIDS patients. It is most closely related to two other
      herpesviruses, the Epstein-Barr virus and herpesvirus saimiri, which are known to
      be associated with lymphomas in humans and nonhuman primates, respectively. To
      determine whether KSHV/HHV-8 is involved in the pathogenesis of mycosis fungoides
      (MF) and related disorders, we used a genomic PCR assay followed by confirmatory
      Southern blot analysis with a nested oligonucleotide probe to analyze cases for
      the presence of this virus. The specimens studied included fresh-frozen lesional
      tissues obtained from 16 patients with MF, seven with lymphomatoid papulosis,
      seven with primary cutaneous CD30+ large cell lymphoma of T-cell lineage, and
      five with Hodgkin's disease. Two T-cell tumor lines were also studied: MT4
      (derived from a patient with adult T-cell leukemia/lymphoma) and Jurkat (derived
      from a patient with T-cell acute lymphoblastic leukemia). All cases were
      uniformly negative for KSHV/HHV-8, whereas Kaposi's sarcoma-positive controls and
      human beta-globin DNA integrity controls were appropriately positive. These
      findings provide strong evidence against a role for KSHV/HHV-8 in the
      pathogenesis of MF or associated lymphoproliferative disorders.

PMID- 9182823
TI  - Organization and nucleotide sequence of the human Hermansky-Pudlak syndrome (HPS)
      gene.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized
      by oculocutaneous albinism, bleeding tendency, and lysosomal ceroid storage
      disease, associated with defects of multiple cytoplasmic organelles-melanosomes,
      platelet-dense granules, and lysosomes. HPS is frequently fatal and is the most
      common single-gene disorder in Puerto Rico. We previously characterized the human
      HPS cDNA and identified pathologic mutations in the gene in patients with HPS.
      The HPS protein is a novel apparent transmembrane polypeptide that seems to be
      crucial for normal organellar development. Here we describe the structural
      organization, nucleotide sequence, and polymorphisms of the human HPS gene. The
      gene consists of 20 exons spanning about 30.5 kb in chromosome segment 10q23.1
      q23.3. One of the intervening sequences is a member of the novel, very rare class
      of so-called "AT-AC" introns, defined by highly atypical 5' and 3' splice site
      and branch site consensus sequences that provide novel targets for possible
      pathologic gene mutations. This information provides the basis for molecular
      analyses of patients with HPS and will greatly facilitate diagnosis and carrier
      detection of this severe disorder.

PMID- 9182824
TI  - Control of hair growth with parathyroid hormone (7-34).
AB  - Parathyroid hormone (PTH) related peptide (PTHrP) is thought to influence the
      proliferation and differentiation of the epidermis and hair follicle. As a means
      of elucidating the biologic function of PTHrP on the hair follicle, a PTHrP
      analog PTH (7-34), which is a PTH/PTHrP receptor antagonist, was given
      intraperitoneally twice daily to C57 BL/6 mice at different stages of the hair
      cycle. PTH (7-34) induced 99 +/- 4.5% (mean +/- SEM) of resting telogen hair
      follicles into a proliferative (anagen) state, whereas 100% of the hair follicles
      in the control group remained in telogen. To determine whether this peptide
      influenced the progression of the hair follicles from anagen to catagen (hair
      follicle maturation and regression), groups of mice that were either
      spontaneously in or induced to anagen received either PTH (7-34) or placebo.
      Morphometric analysis of the hair follicles from the middle back region of the
      spontaneous anagen mice that received PTH (7-34) revealed that 19 +/- 4% (mean +/
      SEM) of the follicles were in anagen VI, whereas none (0%) were in anagen in the
      control group. Similarly, in induced anagen mice treated with PTH (7-34), 22.3 +/
      1.4 (mean +/- SEM) of the follicles were in anagen VI compared to only 1.3 +/-
      0.7% in the control mice. Together these observations suggest that PTHrP is a
      hair follicle morphogen that may be a major factor responsible for controlling
      the hair cycle. These studies provide a new insight for development of PTHrP
      analogs for a wide variety of disorders related to disturbances of hair cycling.

PMID- 9182825
TI  - Treatment of experimental subcutaneous human melanoma with a replication
      restricted herpes simplex virus mutant.
AB  - Modified, non-neurovirulent herpes simplex viruses (HSV) have shown promise for
      the treatment of brain tumors, including intracranial melanoma. In this report,
      we show that HSV-1716, an HSV-1 mutant lacking both copies of the gene coding
      infected cell protein 34.5 (ICP 34.5), can effectively treat experimental
      subcutaneous human melanoma in mice. In vitro, HSV-1716 replicated in all 26
      human melanoma cell lines tested, efficiently lysing the cells. Therapeutic
      infection of subcutaneous human melanoma nodules with HSV-1716 led to viral
      replication that was restricted to tumor cells by immunohistochemistry. Moreover,
      HSV-1716 treatment significantly inhibited progression of preformed subcutaneous
      human melanoma nodules in SCID mice and caused complete regression of some
      tumors. This work expands the potential scope of HSV-1-based cancer therapy.

PMID- 9182826
TI  - Identification of novel glucocorticoid-response elements in human elastin
      promoter and demonstration of nucleotide sequence specificity of the receptor
      binding.
AB  - Glucocorticoids exert their action on gene expression through activation of
      cytoplasmic glucocorticoid receptors (GRs) that bind to glucocorticoid response
      elements (GREs). The consensus GRE consists of two half sites (underlined),
      AGAACANNNTGTTCT. We have recently cloned the entire human elastin gene.
      Nucleotide sequencing of the promoter region disclosed the presence of three
      putative GREs with the downstream half-site sequence TGTTCC that has homology
      with the consensus GRE, although the upstream half site showed no homology. To
      examine the functionality of these putative GREs in binding to the GRs, we
      performed gel mobility shift and supershift assays with synthetic oligomers
      containing the putative GREs and a recombinant GR protein, expressed in a
      baculovirus system. All three GREs identified in the elastin promoter bound the
      receptor. A chimeric oligonucleotide containing the upstream consensus GRE half
      site and the downstream elastin promoter GRE half site was capable of binding the
      receptor, and this binding could be competed with the elastin promoter GRE.
      Nonconservative substitution of single nucleotides (positions 1-6) in the elastin
      GRE indicated that mutations in the positions 1-3 and 6 had relatively little
      effect, but substitutions in positions 4 and 5 rendered the oligomer less
      effective in competing for the binding. These observations suggest that the
      downstream half site of GREs in the human elastin promoter is sufficient for
      receptor binding and certain nucleotides are critical for the efficient binding.
      The results also imply that the three GREs within the human elastin promoter are
      active and mediate the glucocorticoid-induced up-regulation of human elastin
      promoter activity.

PMID- 9182827
TI  - Novel ITGB4 mutations in a patient with junctional epidermolysis bullosa-pyloric
      atresia syndrome and altered basement membrane zone immunofluorescence for the
      alpha6beta4 integrin.
AB  - Immunofluorescence studies of junctional epidermolysis bullosa with pyloric
      atresia (JEB-PA) have suggested abnormalities in the expression of the alpha6
      beta4 integrin, an integral component of hemidesmosomes. In this study, we
      examined a family with two affected individuals with JEB-PA for mutations in the
      ITGA6 and ITGB4 genes which encode the alpha6 and beta4 integrin polypeptides,
      respectively. Mutation detection strategy based on PCR amplification of genomic
      DNA, followed by heteroduplex analysis and direct nucleotide sequencing, did not
      reveal sequence variants in ITGA6. Putative pathogenic mutations, however, were
      identified in both ITGB4 alleles. Specifically, the proband was a compound
      heterozygote for a 1-bp maternal deletion, 3434delT, and an 8-bp paternal
      deletion, 4050de18. Both mutations result in a frameshift and premature
      termination codon downstream from the deletion. At the protein level,
      immunofluorescence of the skin of the proband revealed negative staining for the
      integrin alpha6 and markedly reduced staining for the beta4 subunit. Thus, the
      results support the notion of close association of the alpha6 beta4 integrin
      subunits and further attest to the critical role of this integrin in providing
      physiologic stability to the dermal-epidermal junction.

PMID- 9182829
TI  - Further evidence for ultraviolet light induction of CDKN2 (p16INK4) mutations in
      sporadic melanoma in vivo.

PMID- 9182828
TI  - A glycine-to-arginine substitution in the triple-helical domain of type VII
      collagen in a family with dominant dystrophic epidermolysis bullosa pruriginosa.
AB  - Epidermolysis bullosa pruriginosa is a recently recognized variant of dystrophic
      epidermolysis bullosa (DEB) characterized by severe pruritus and scarring, mainly
      involving the extensors of the extremities. In this study, we searched for
      mutations in the type VII collagen gene (COL7A1) using polymerase chain reaction
      amplification of exonic segments of COL7A1, followed by heteroduplex analysis, in
      a Chinese pedigree with dominant DEB displaying a striking anastomosing network
      of lichenoid papules and scarring. The study revealed a G-to-A transition at
      nucleotide 6724 within exon 85 of COL7A1, converting a glycine to an arginine
      (G2242R) within the triple-helical domain of the type VII collagen in affected
      individuals. These findings demonstrate that EB pruriginosa in this family is a
      clinical variant of dominant DEB.

PMID- 9182830
TI  - Formation, intracellular distribution and efflux of glutathione-bimane conjugates
      in drug-sensitive and -resistant MCF-7 cells.
AB  - The rate of reaction of monochlorobimane with glutathione (GSH) was measured in
      native human mammary MCF-7 adenocarcinoma cells (MCF-7wt) and sublines displaying
      resistance to 4-hydroperoxycyclophosphamide (MCF-7hc) and adriamycin (MCF-7adr)
      prior to examination by epifluorescence and confocal microscopy. After a 60-min
      incubation period at 37 degrees C, essentially all GSH was conjugated in the MCF
      7wt and MCF-7adr cell lines whereas only 80% of the GSH was conjugated in the MCF
      7hc line. All three lines displayed significant export of the conjugate from the
      cell during this period, with the MCF-7adr line displaying the most rapid efflux
      with 85% of the conjugate exported within 60 min. Epifluorescence microscopy
      detected an approximately 20% increase in integrated fluorescence intensity in
      the nuclear region in all three lines. Confocal microscopy however, indicated
      that most of the cells examined showed a homogeneous fluorescence distribution.
      The cells grown in monolayers were found to be thicker in the nuclear region
      suggesting that the observed increase in fluorescence intensity in the nuclear
      region in the images from epifluorescence microscopy was probably derived from
      fluorescence from an out-of-focus plane. Cells depleted of GSH with buthionine
      sulfoximine followed by treatment with mBCl showed significant fluorescence
      intensity resulting from nonspecific binding of this probe. These studies
      illustrate the need for measuring the rate of GSH conjugate export and for
      determining probe specificity, and emphasizes the need for using confocal
      techniques for the quantitative evaluation of the distribution of intracellular
      fluorescence.

PMID- 9182832
TI  - Inter- and intraindividual variation in dihydropyrimidine dehydrogenase activity
      in peripheral blood mononuclear cells.
AB  - PURPOSE: The activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting
      enzyme in fluorouracil catabolism, has been reported to vary according to time of
      day. We wished to determine whether peak and trough DPD activities occurred at
      uniform times in six subjects, whether individual patterns fit a discernible
      profile, and whether such patterns were consistent and reproducible over time.
      METHODS: Mononuclear cells were isolated from peripheral blood at 3-h intervals
      over a 24-h period on three different dates over a 6-month period. DPD activity
      was determined by incubating cellular lysates with [3H]FUra and measuring
      [3H]dihydrofluorouracil formation over time. RESULTS: When the data were averaged
      by study date for each subject, the median value for the average DPD activity
      (11.0 pmol/min per 10(6) cells) was significantly different from both the median
      peak (21.1 pmol/min per 10(6) cells, P = 0.004) and median trough activities (4.0
      pmol/min per 10(6) cells, P = 0.002). Within the six subjects, the average DPD
      activity for the three study dates differed by a median of 2.4-fold (range 1.2-
      to 4.8-fold). The time at which peak and trough DPD activities occurred varied
      between subjects: 8 of the 17 peaks (47%) occurred between 10:00 p.m. and 6:00
      a.m., 6 (35%) occurred between 8:00 a.m. and 3:00 p.m., and 3 (18%) occurred
      between 5:00 p.m. and 8:15 p.m. Thus, the time of day when the peak occurred was
      essentially randomly distributed over the 24-h period of observation (P = 0.68).
      Ten (59%) of the trough DPD activities occurred between 7:00 a.m. and 3:00 p.m.
      The median interval between the peak and trough was 6.5 h. The data were also
      expressed as percent of the mean for each individual's 24-h sampling period, and
      reordered as time from peak rather than as the actual time of day. When the
      combined data for all cycles was considered, the trough occurred 6-9 h after the
      peak, and the DPD levels subsequent to the peak did not display merely random
      variation (P = 0.0055). CONCLUSIONS: DPD activity levels and the times at which
      peak and trough DPD activities occurred varied both between and within subjects.
      If fluctuations in DPD activity influence the tolerability of fixed-rate
      infusions of FUra, these data suggest that a single variable-rate infusion
      regimen may not be suitable for all patients nor for a given individual treated
      over several months.

PMID- 9182831
TI  - Enhancement of therapeutic efficacy of bleomycin by incorporation into
      biodegradable poly-d,l-lactic acid.
AB  - A new system for the delivery bleomycin (BLM) to target lesions was established
      by incorporating BLM into a small cylinder of a biodegradable polylactic acid
      (PLA) of low molecular weight. Cross-sectional analysis of the system (BLM-PLA)
      showed that BLM particles were uniformly enclosed in the PLA matrix. In vitro
      studies demonstrated that BLM was released continuously for more than 3 weeks
      from BLM-PLA immersed in saline. BLM-PLA was implanted subcutaneously into the
      backs of rats. A high concentration of BLM was maintained in the connective
      tissues near the implants for 2 weeks. In contrast, the level of BLM activity was
      low when a BLM solution (BLM-SOL) was administered subcutaneously by injection.
      The concentration of BLM in the abdominal lymph nodes was significantly higher
      following BLM-PLA implantation than following subcutaneous BLM-SOL injection. The
      inhibitory effects of BLM-PLA and BLM-SOL on tumor growth were compared with no
      treatment using a subcutaneously transplanted Yoshida sarcoma. The antitumor
      effect of BLM-PLA was significantly higher than that of BLM-SOL and no treatment.
      BLM-PLA also resulted in a more favorable distribution of BLM than BLM-SOL. Thus,
      BLM-PLA proved to be effective in controlling this experimentally transplanted
      tumor.

PMID- 9182833
TI  - Disposition of leucovorin and its metabolites in dietary folic acid-deplete mice 
      comparison between tumor, liver, and plasma.
AB  - PURPOSE: A comprehensive pharmacokinetic study of leucovorin (5
      formyltetrahydrofolate, 5-HCO-FH4) and its metabolites was conducted in plasma,
      liver and implanted tumor tissue from mice maintained on a low folic acid diet.
      While it has been previously demonstrated that the antitumor activity of
      fluorouracil (FU) can be potentiated by 5-HCO-FH4, the optimum time for
      administration of FU after 5-HCO-FH4, to maximally elevate the active folate
      metabolite methylenetetrahydrofolate in tumor has not been established. Human
      plasma studies have defined the pharmacokinetics of circulating 5-HCO-FH4 and its
      metabolites, but comparison with human tumor accumulation has not been
      practicable because of sampling difficulties. As an alternative, a mouse model
      system, based on low dietary folic acid, was used to evaluate plasma, liver and
      implanted tumor reduced folates after administration of 5-HCO-FH4. METHODS:
      Plasma and tissue samples were collected from folate-deplete mice over a 12-h
      period after intraperitoneal administration of 90 mg/kg [R, S] 5-HCO-FH4. Reduced
      folates were evaluated using a ternary complex assay. RESULTS: The time at which
      maximal accumulation of parent compound and all metabolites, except 5
      methyltetrahydrofolate (5-CH3FH4), occurred in tumor was the same as in plasma.
      Alternatively, peak liver accumulation was delayed relative to plasma for all
      folates except 5-CH3FH4. CONCLUSIONS: The results suggest that mouse plasma
      accumulation of reduced folates, with the exception of 5-CH3FH4, can predict
      tumor accumulation. Hence, evaluation of human plasma folate accumulation may
      potentially provide a means to improve the timing of the administration of FU
      relative to 5-HCO-FH4 to achieve a superior therapeutic outcome.

PMID- 9182834
TI  - Chemical characterization and comparative cellular effects of meta-iodobenzyl
      guanidine and benzyl guanidine.
AB  - meta-Iodobenzyl guanidine (MIBG) combines the structural properties of the neuron
      blocking agents bretylium and guanethidine and is being used increasingly for
      various clinical applications. Different samples of MIBG were assayed for
      possible contamination with benzyl guanidine (BG). Fast-atom-bombardment mass
      spectrometry (FAB-MS) analysis showed a prominent but variable m/z 150 signal,
      corresponding to a protonated BG. The MS/MS fragmentation pattern of these [M +
      H]+ ions was similar to that obtained from FAB-MS-generated, protonated BG,
      confirming the proposed molecule and associated structures. RP-HPLC analysis of
      both guanidines, however, excluded the possibility of contamination of MIBG with
      BG. It was therefore concluded that the BG signal was an artifact of the FAB-MS
      procedure. In addition, the importance of the meta-substituted iodine for the
      biological activity of MIBG was investigated. Three different biochemical and
      cell-biological properties of MIBG were compared with those of its precursor MIBA
      and BG. The assays used were: inhibition of the catecholamine "Uptake I" system
      in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells, inhibition of
      mitochondrial respiration, and general cytotoxicity in L1210 leukemia cells. Of
      the drugs tested, MIBG was the most efficient in Uptake I inhibition and was more
      toxic in survival assays, but as compared with BG it was almost equipotent in
      inhibiting mitochondrial respiration. These findings contribute to a further
      elucidation of the mechanism by which MIBG exerts its various actions.

PMID- 9182835
TI  - Mechanism of action and spectrum of cell types susceptible to doxorubicin
      photochemotherapy.
AB  - We have shown that, whereas argon ion laser irradiation alone is not cytocidal
      for L929 cells, it greatly increases the cytotoxicity of intracellular
      doxorubicin. The present study showed that light enhancement of doxorubicin
      cytotoxicity was not restricted to stock L929 cells, but could also be
      demonstrated using L929 cells selected for doxorubicin resistance and several
      standard cell lines that are relatively resistant to doxorubicin prior to
      selection. Light-enhanced cytotoxicity resulted in extensive nuclear DNA loss and
      was strongly inhibited by anoxia. These findings suggest that the mechanism by
      which light exposure enhances doxorubicin cytotoxicity involves DNA damage by
      intranuclear generation of reactive oxygen species.

PMID- 9182836
TI  - A Bayesian dosing method for carboplatin given by continuous infusion for 120 h.
AB  - Carboplatin (CBDCA), an analogue of cisplatin, exhibits reduced toxicity but wide
      interpatient variability of its pharmacokinetic parameters. Individualization of
      the CBDCA dose is therefore necessary. Although various formulas have been
      developed for this purpose, major side effects have been reported on CBDCA
      administration by short-term infusion (0.5 or 1 h). We therefore propose a new
      schedule of CBDCA administration. Instead of a dosing method based on the
      estimation of renal function when a classic administration schedule is used, we
      propose a pharmacokinetic dosing method (Bayesian method), whereby CBDCA is given
      by continuous infusion for 120 h. First, CBDCA was given to 21 patients to
      determine the population pharmacokinetic parameters of carboplatin. Then, on the
      basis of total platinum plasma concentration measurements and Bayesian estimation
      of pharmacokinetic parameters, it was possible to individualize the CBDCA dose
      within the first 24 h of the infusion. This new protocol for CBDCA administration
      was evaluated in 36 new patients (60 courses). Three theoretical end points at
      the end of the infusion were considered. For a given theoretical end point, 20
      courses were taken into account. The theoretical end points (i.e., 1, 1.5, and
      1.8 mg/l) were compared with the concentrations measured at the end of the
      infusion, which were 0.99 +/- 0.10, 1.41 +/- 0.13, and 1.72 +/- 0.20 mg/l,
      respectively. This Bayesian dosing method can easily be used in clinical
      practice, and the determination of predictive performances has shown that the
      method is precise and unbiased. With no more toxicity or practical difficulties
      than those produced by other methods, and with acceptable tolerance, it was
      possible to reach a median dose that was 20% higher than the usual dose (484 +/-
      190 mg/m2 as compared with 400 mg/m2). In conclusion, this new schedule of CBDCA
      administration appears to be interesting in terms of tolerance. However, new
      studies are required to confirm that this new scheme leads to equal or better
      efficacy than the classic protocol.

PMID- 9182837
TI  - Probenecid reverses multidrug resistance in multidrug resistance-associated
      protein-overexpressing HL60/AR and H69/AR cells but not in P-glycoprotein
      overexpressing HL60/Tax and P388/ADR cells.
AB  - PURPOSE: To determine whether probenecid, an inhibitor of organic anion
      transport, is able to reverse multidrug resistance (MDR) through modulation of
      the drug transport function of MDR-associated protein (MRP) and P-glycoprotein (P
      gP). METHODS: Two MRP-overexpressing cell lines (HL60/AR and H69/AR) and two P-gP
      overexpressing cell lines (HL60/Tax and P388/ADR) were cultured with different
      concentrations of daunorubicin (DNR) or vincristine (VCR) in the presence or
      absence of various concentrations of probenecid (0.01-10 mM). Drug sensitivity
      was determined using an MTT assay. DNR accumulation and subcellular distribution
      were determined by flow cytometry and confocal microscopy respectively. VCR
      accumulation was determined by scintillation spectrometry. RESULTS: Probenecid,
      in a concentration-dependent manner, reversed resistance to DNR and VCR in
      HL60/AR and H69/AR tumor cell lines. This effect of probenecid on MDR was
      associated with an increased accumulation of DNR and VCR and correction of the
      altered subcellular distribution of DNR. The concentrations of probenecid that
      reversed MDR are clinically achievable in vivo. In contrast, probenecid did not
      reverse MDR in either HL60/Tax or P388/ADR tumor cell lines that overexpress P
      gP. CONCLUSION: These results suggest that probenecid is an effective
      chemosensitizer of MRP-associated MDR tumor cells and is a potential candidate
      for clinical use to reverse MDR.

PMID- 9182838
TI  - Cell cycle perturbations in cisplatin-sensitive and resistant human ovarian
      carcinoma cells following treatment with cisplatin and low dose rate irradiation.
AB  - PURPOSE: To investigate cell cycle pertubations in plateau-phase human ovarian
      carcinoma cells following treatment with cisplatin, low dose-rate irradiation
      (LDRI), or combined cisplatin and LDRI, in order to understand cell cycle
      mechanisms by which these two treatment modalities interact. METHODS: Human
      ovarian carcinoma cells sensitive (A2780) and resistant (2780CP) to cisplatin
      were grown to plateau phase and given protracted cisplatin treatments (A2780 0.7
      and 2 microg/ml; 2780CP 5 and 15 microg/ml) and/or LDRI (0.41 cGy/min). Cell
      cycle distribution following treatment was determined by two-parameter flow
      cytometry, based on bromodeoxyuridine (BrdU) uptake and DNA content using
      propidium iodide staining. RESULTS: The cisplatin-sensitive A2780 cells exposed
      to cisplatin alone for up to 28 h showed depletion of the G1 fraction and
      accumulation in S-phase, although the percentage of S-phase cells actively
      incorporating BrdU dropped to almost zero. The cisplatin-resistant 2780CP cells
      exposed to cisplatin alone showed a G1 arrest when exposed to 15 microg/ml, but
      not when exposed to 5 microg/ml. LDRI alone caused little cell cycle
      redistribution different from controls in either cell line. When LDRI was
      combined with cisplatin, no significant cell cycle redistribution was observed,
      apart from a decline in the actively incorporating S-phase fraction. CONCLUSIONS:
      Cisplatin caused A2780 cells to accumulate in nonincorporating S-phase, with no
      evidence of G1 arrest. Cisplatin-resistant 2780CP cells showed a G1 block when
      exposed to a high enough cisplatin concentration. This could indicate a mechanism
      of cisplatin resistance in these cells. LDRI alone or in combination with
      cisplatin did not result in significant cell cycle redistribution.

PMID- 9182839
TI  - In vitro studies of the hyperthermic enhancement of activated ifosfamide (4
      hydroperoxy-ifosfamide) and glucose isophosphoramide mustard.
AB  - PURPOSE: To study the effect of hyperthermia on the cytotoxicity of glucose
      isophosphoramide mustard (D-19575), a derivative of ifosfamide, which does not
      require activation and preclinically demonstrates less nephrotoxicity and
      myelosuppression than ifosfamide. METHODS: In vitro studies (using a crystal
      violet cell survival assay) of the interaction of hyperthermia with D-19575, as
      well as the activated form of ifosfamide (4-hydroperoxy-ifosfamide, D-18851),
      were performed using L929 and OVCAR-3 cell lines held at various temperatures
      (i.e. 37 degrees C (control), 40.5 degrees C, 41.8 degrees C, 42.5 degrees C, and
      43 degrees C) for 65 min. RESULTS: The following thermal enhancement ratios (TER)
      were demonstrated: D-19575 in L929 1.2, 2.0 and 2.3 at 40.5, 41.8 and 42.5
      degrees C, respectively; for D-18851 in L929 1.7 at 41.8 degrees C; for D-19575
      in OVCAR-3 2.1, 3.2 and 3.3 at 40.5, 41.8 and 42.5 degrees C, respectively; for D
      18851 in OVCAR-3 4.6 at 41.8 degrees C. CONCLUSION: The significant observed
      increase in cytotoxicity of D-19575 caused by hyperthermia taken together with
      its known preclinical toxicity profile, encourage its further preclinical and
      ultimately clinical testing, including its use with whole body and regional
      hyperthermia.

PMID- 9182840
TI  - Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the
      proliferation of three prostate cancer cell lines.
AB  - PURPOSE: Polyamines are biologic cations necessary for normal cell growth.
      Polyamine analogues have been shown to be effective inhibitors of tumor growth.
      We tested the effect of the polyamine analogues 1,1 9-bis(ethylamino)-5,10,15
      triazanonadecane (BE-4-4-4-4), N1,N11-bis(ethyl)norspermine (BE-3-3-3) and 1,15
      bis(ethylamino)-4,12-diazapentadecane (BE-3-7-3) on the growth of the prostate
      cancer cell lines DU145, LNCaP and PC-3 in vitro. We also tested the effect of BE
      4-4-4-4 on androgen-independent DU145 cells in vivo via a nude mouse xenograft
      model. METHODS: In vitro, cell proliferation was measured using a DNA assay or a
      colony-formation assay. In vivo, mice were given saline or BE-4-4-4-4 3 mg/kg or
      5 mg/kg intraperitoneally twice daily on days 7-10 and 14-17 (cycle 1), days 49
      52 and 56-59 (cycle 2) and days 91-94 and 98-101 (cycle 3). RESULTS: The
      proliferation of DU145, LNCaP and PC-3 prostate cancer cell lines was inhibited
      in a dose-dependent manner by BE-4-4-4-4. Intracellular putrescine, spermidine
      and spermine levels in all three cell lines declined after only 24 h exposure to
      BE-4-4-4-4 in vitro. Animals receiving BE-4-4-4-4 showed inhibition of tumor
      growth which continued throughout the experiment with 74% (3 mg/kg) and 81% (5
      mg/kg) growth inhibition seen on day 101. No overt toxic reactions besides weight
      loss were observed in BE-4-4-4-4-treated animals. Tumor tissue from animals
      treated with BE-4-4-4-4 showed a dose-dependent decrease in spermidine and
      spermine levels but no decline in putrescine levels as compared with control. BE
      4-4-4-4 levels were highest in tumors on day 63 with levels reaching 0.33 and
      1.45 nmol/mg protein from animals treated at the 3 mg/kg and 5 mg/kg doses,
      respectively. CONCLUSION: These results show the polyamine analogues BE-4-4-4-4,
      BE-3-3-3 and BE-3-7-3 to be effective inhibitors of prostate cancer cell growth
      in vitro and BE-4-4-4-4 to be an effective inhibitor of DU145 cells in vivo with
      minimal toxicity.

PMID- 9182841
TI  - In vitro antitumor activity of 3'-desamino-3'(2-methoxy-4-morpholinyl)
      doxorubicin on human melanoma cells sensitive or resistant to triazene compounds.
AB  - A new methoxymorpholinyl derivative of Adriamycin (ADR), FCE 23762 (MRD), has
      recently been selected for phase I clinical trials for its reduced cardiotoxicity
      and for its cytotoxic activity against a broad spectrum of solid tumors and
      leukemias that are sensitive or resistant to ADR. The purpose of the present
      study was to compare the in vitro antitumor activity of MRD and ADR on human
      melanoma lines with different chemosensitivity to triazene compounds, among which
      dacarbazine remains a reference drug in the treatment of melanoma. Both MRD and
      ADR were tested in vitro on three melanoma lines, MI13443-MEL, SK-MEL-28, and
      M14, previously screened for their chemosensitivity to the triazene compound p-(3
      methyl-1-triazeno) benzoic acid, potassium salt (MTBA). The three lines were also
      analyzed for P-170 expression, total glutathione (GSH) content, and GSH-related
      enzyme activity. All melanomas, whether sensitive or resistant to MTBA, were
      susceptible to anthracycline treatment. The cytotoxic activity of MRD was
      comparable with that of ADR, and no substantial difference was found in cell
      growth inhibition between the two drugs. When the relative chemosensitivity of
      the three lines was considered, SK-MEL-28 was found to be slightly less sensitive
      to MRD treatment than the other tumors. This finding seems to correlate with the
      higher GSH-peroxidase activity of this melanoma relative to that of the MI13443
      and M14 lines. These results show a homogeneous response of melanoma lines to MRD
      treatment in vitro, suggesting that phase I clinical trials concerning this drug,
      which in vivo appears to be activated to a more cytotoxic metabolite, could be
      extended to metastatic melanomas, including those completely resistant to
      triazene compounds.

PMID- 9182842
TI  - Influence of age on toremifene pharmacokinetics.
AB  - Toremifene pharmacokinetics were compared in ten healthy young men (< 33 years)
      and elderly women (< 65 years). A single oral 120-mg dose of toremifene was given
      after an overnight fast and blood samples were collected over 28 days. Serum
      levels of the parent drug and the metabolites were determined; appropriate
      pharmacokinetic parameters were calculated and statistically evaluated.
      Toremifene peak concentrations (average 640 ng/ml) were achieved at 3.5 h. The
      area under the curve (AUC) and the apparent oral clearance were comparable in the
      young and elderly subjects. The half-life was prolonged (4.2 versus 7.2 days) and
      the apparent volume of distribution was increased (457 versus 627 1) in the
      elderly. The peak concentration of the main metabolite N-demethyltoremifene was
      lower (159 versus 233 ng/ml) and the half-life was prolonged (8.3 versus 19.1
      days) in the elderly subjects, but the AUC values were comparable. The results
      suggest that toremifene is distributed more widely in the elderly but that its
      clearance is unaffected by age. It is concluded that the dosage requirement of
      the drug is unlikely to differ between young and elderly subjects.

PMID- 9182843
TI  - Evidence that perihypoglossal neurons involved in vestibular-auditory and gaze
      control functions respond to nerve growth factor.
AB  - Nerve growth factor (NGF), which has long been considered to be a trophic factor
      for peripheral sensory and sympathetic neurons, has been found recently to
      influence cholinergic neurons in the basal forebrain and neostriatum. In the
      present study, we provide evidence that brainstem neurons in the perihypoglossal
      area that relay information from the inner ear and vestibular apparatus to the
      cerebellum and tectum are responsive to NGF. These neurons, which are located in
      the nucleus prepositus hypoglossi (NPH), spinal vestibular nucleus, cochlear
      complex, and gigantocellular and paragigantocellular nuclei of the reticular
      formation, express functional receptors for NGF and up-regulate the expression of
      trkA receptors after injection of NGF into targets. In addition, the
      developmental up-regulation of NGF in the cerebellum coincides with the
      differentiation of the perihypoglossal nuclei. These results suggest that neurons
      representing the principal brain relays for auditory and vestibular pathways and
      perihypoglossal neurons involved in gaze coordination are a novel group of
      central neurons (besides cholinergic neurons in the basal forebrain and
      neostriatum) that respond to NGF.

PMID- 9182844
TI  - Nitric oxide synthase in learning-relevant nuclei of the chick brain: morphology,
      distribution, and relation to transmitter phenotypes.
AB  - Nitric oxide (NO) has been implicated in learning in the hatchling chicken. To
      examine morphological and neurochemical properties of neurons that contain NO
      synthase (NOS) in brain regions known to be involved in learning and memory, the
      NADPH-diaphorase technique was used in conjunction with immunocytochemistry and
      tract tracing. A distinct cell type was NOS-labeled in the lobus parolfactorius
      (LPO) in the telencephalon, and neurons were labeled in the area ventralis of
      Tsai (AVT), the substantia nigra (nucleus tegmenti pedunculo-pontinus, pars
      compacta, TPc), and the locus coeruleus in the brainstem. Thus, NO may influence
      processes of learning and memory in the forebrain after release from intrinsic
      neurons and/or from extrinsic NOS-projections originating from the brainstem. DiI
      tracing revealed that most of the NOS-positive neurons in the AVT/TPc project to
      the basal forebrain. The majority of tyrosine hydroxylase-positive (presumptive
      dopaminergic) neurons in the AVT and TPc expressed NOS. Double-labeling with
      antibodies to tyrosine hydroxylase, choline acetyltransferase, somatostatin, and
      the neurotrophin receptor as a marker for noradrenergic coeruleus neurons showed
      that NOS was not colocalized with noradrenergic or somatostatinergic neurons, and
      that less than a third of the cholinergic neurons were double-labeled for NOS.
      Injections of 6-hydroxydopamine into the brainstem did not reduce the density of
      NOS-labeled fibers in the LPO, indicating that most of the NO in the LPO
      originates from intrinsic neurons in the basal forebrain. Thus, NOS-containing
      presumptive local circuit neurons in the LPO are the most likely source of NO
      involved in learning of passive avoidance tasks in hatchling chicks.

PMID- 9182845
TI  - NK1 receptor expression in the interstitial cells of Cajal and neurons and
      tachykinins distribution in rat ileum during development.
AB  - The origin and function of the interstitial cells of Cajal (ICCs) that are
      located at the level of the deep muscular plexus (DMP) have not been completely
      identified. It has been recently reported that these cells express neurokinin-1
      (NK1) receptors to which substance P (SP) shows the highest affinity. Studies
      during pre- and postnatal life have demonstrated that ICCs are identifiable in
      the rat ileum soon after birth and already show adult features at 7 days of
      postnatal life. Several neurotransmitters have been identified at the DMP which
      appear at specific times during development. We have studied the expression of
      NK1 receptors by ICCs and enteric neurons and the timing of the appearance of SP
      in the DMP, myenteric plexus (MP) and submucous plexus (SMP) of rat ileum during
      development. Rats, aged from 18 days of fetal life to adulthood, were used. NK1
      receptors and SP were identified by using NK1 polyclonal antibodies and
      tachykinin (SP/TK) polyclonal antibodies, respectively. NK1-immunoreactivity (IR)
      was detected in the ICCs immediately after birth and reached maximal intensity at
      7 days. From birth, SP/TK-IR fibers originated from short excitatory neurons at
      the MP and reached the DMP at 1 week of postnatal life. NK1- and SP/TK-IR
      appeared in the MP neurons in the fetus and in the SMP neurons at weaning. The
      present study demonstrates that by the first days of postnatal life, the NK1-IR
      might be used as a marker of the ICCs at the DMP and suggests that these cells
      may participate in the actions exerted by tachykinins on muscle cells.

PMID- 9182846
TI  - GABAergic and other noncholinergic basal forebrain neurons, together with
      cholinergic neurons, project to the mesocortex and isocortex in the rat.
AB  - The extrathalamic relay from the brainstem reticular formation to the cerebral
      cortex in the basal forebrain has been thought to be constituted predominantly,
      if not exclusively, by cholinergic neurons. In contrast, the septohippocampal
      projection has been shown to contain an important contingent of gamma
      aminobutyric acid (GABA)ergic neurons. In the present study, we investigated
      whether GABAergic neurons also contribute to the projection from the basal
      forebrain to neocortical regions, including the mesocortex (limbic) and the
      isocortex in the rat. For this purpose, retrograde transport of cholera toxin
      (CT) was examined from the medial prefrontal cortex for the mesocortex and from
      the parietal cortex for the isocortex and was combined with dual
      immunohistochemical staining for either choline acetyltransferase (ChAT) or
      glutamic acid decarboxylase (GAD) in adjacent series of sections. Retrogradely
      labelled GAD+ neurons were codistributed with retrogradely labelled ChAT+ neurons
      through the basal forebrain from both the prefrontal and the parietal cortex,
      suggesting parallel, widespread cortical projections. The GAD+ cortically
      projecting cells were similar in size to the ChAT+ cells, thereby indicating that
      they comprise a contingent of the magnocellular basal cell complex. The
      proportions of retrogradely labelled neurons that were GAD+ (approximately one
      third) were equal to or greater than those that were ChAT+ from both the
      prefrontal cortex and the parietal cortex. In addition, the total of GAD+ and
      ChAT+ neurons did not account for the total number of cortically projecting
      cells, indicating that another equivalent proportion of chemically unidentified
      noncholinergic neurons also contributes to the basalocortical projection.
      Accordingly, as in the allocortex, GABAergic, cholinergic, and other unidentified
      noncholinergic neurons may have the capacity to modulate activity in the
      mesocortex (limbic) and the isocortex through parallel, widespread projections.

PMID- 9182848
TI  - Antennal lobe neurons of the honey bee, Apis mellifera, express a D2-like
      dopamine receptor in vitro.
AB  - We have used the D2-specific dopamine receptor ligand spiperone [N-(p
      aminophenethyl) spiperone; NAPS] coupled to the fluorophore 7-nitrobenz-2-oxa-1,3
      diazole-4-yl (NBD) to visualize dopamine receptors expressed in vitro by neurons
      of the primary antennosensory centers (antennal lobes) of the brain of the honey
      bee, Apis mellifera. Changes in the percentage of antennal lobe neurons
      exhibiting spiperone binding sites over time in culture and at different stages
      of metamorphic adult development have been investigated. Neurons obtained from
      animals at all stages of development exhibited spiperone binding sites, but only
      after 2 days or more in vitro. The percentage of antennal lobe neurons in vitro
      expressing spiperone binding sites increased significantly with the development
      of the antennal lobe neuropil. Fluorescently labelled spiperone (120 nM) could be
      displaced effectively by 1 mM dopamine but not by the same concentration of
      tyramine, octopamine, or serotonin. In addition, the D2 antagonist spiperone and
      the D2/D1 antagonist fluphenazine were more effective at displacing the
      fluorescent ligand than the D1-specific antagonist SCH23390. Our results indicate
      that Apis antennal lobe neurons in culture express a dopamine receptor and that
      this receptor is more likely to be D2-like than D1-like in nature. The receptor
      is expressed early in the metamorphic adult development of the antennal lobe
      neuropil of the brain.

PMID- 9182847
TI  - GABA immunoreactivity in hypothalamic neurons and growth cones in early
      development in vitro before synapse formation.
AB  - GABA (gamma-aminobutyrate) is the most prevalent inhibitory transmitter in the
      mature hypothalamus. In contrast, in the developing hypothalamus, GABA may exert
      depolarizing actions leading to neuronal excitation. To determine whether GABA is
      present in hypothalamic neurons early in development, and whether there is a
      preferential expression in axonal growth cones, immunogold and peroxidase studies
      were used with light and whole mount transmission electron microscopy. At
      embryonic day 15, a stage of development at the beginning of hypothalamic
      neurogenesis, histological sections showed GABA immunoreactivity in fibers and
      weakly stained perikarya. Hypothalamic neurons (13%) cultured at embryonic day 15
      were immunoreactive after 1 day in vitro. The percentage of neurons stained, and
      the intensity of staining increased during the next few days to 39% at 4 days in
      vitro. Neuritic growth cones, including lamellipodia and long filopodia, showed
      strong immunoreactivity before synaptogenesis. By using neuronal whole mounts
      studied with transmission electron microscopy and GABA silver-enhanced immunogold
      staining, a quantitative comparison of growth cones after a day and a half in
      culture revealed that the growth cone of the longest process, the putative axon,
      had a greater level of immunogold labeling than that of the shorter processes,
      the putative dendrites. This finding is one of the earliest biochemical
      differences between putative axons and dendrites. Astrocytes in the same cultures
      showed no immunolabeling. These results indicate that GABA is present very early
      in the development of hypothalamic neurons and is in a position to be released.

PMID- 9182849
TI  - Developmental expression of GABA(A) receptor subunit and GAD genes in mouse
      somatosensory barrel cortex.
AB  - In situ hybridization histochemistry with radioactive cRNA probes was used to
      study patterns of gene expression for alpha1, alpha2, alpha4, alpha5, beta1,
      beta2, and gamma2 subunit mRNAs of typeAgamma aminobutyric acid (GABA(A))
      receptors and for 67-kDa glutamic acid decarboxylase (GAD67) mRNA in mouse barrel
      cortex during the period (postnatal days 1-12; P1-P12) when thalamocortical
      innervation of layer IV barrels is occurring. The alpha1, beta2, and gamma2
      subunit mRNAs increased substantially with age, especially in layers V and VI,
      and throughout the period studied, invariably had the same laminar-specific
      patterns of expression. All three mRNAs were highly expressed in the dense
      cortical plate at P1. In layer IV after differentiation of barrels, they were
      expressed in cells of both barrel walls and hollows but especially in the walls.
      The alpha2, alpha4, alpha5, and beta1 subunit mRNAs were expressed at lower
      levels and had different laminar patterns of distribution; alpha2 and alpha4
      showed switches between layers over time; alpha5 was invariably associated with
      the subplate or its derivative, beta1 with layer IV. Levels of alpha2 mRNA did
      not change over time; alpha4 and beta1 mRNAs increased and alpha5 decreased.
      GAD67 mRNA was highest in layer I at P1 and progressively increased in other
      layers. These results suggest that postnatal development of GABA(A) receptors is
      mainly directed at the production of receptors assembled from alpha1, beta2, and
      gamma2 subunits, with beta1 contributing in layer IV. Other subunits may be
      associated with receptors involved in trophic actions of GABA during development
      and may give GABA(A) receptor-mediated responses in the developing cortex their
      particular physiological profile.

PMID- 9182850
TI  - Concurrent cellular output from two proliferative populations in the early
      embryonic mouse corpus striatum.
AB  - In mice, the striatal compartment of the forebrain is established by embryonic
      day 11 (E11, E0 = day of conception) when a lateral ganglionic eminence emerges
      surrounding the lateral and ventral margins of the forebrain ventricles. The
      inception of the striatal compartment is evidence of altered cell cycle kinetics,
      especially a rapid production of postmitotic cells, within a discrete portion of
      the telencephalic neuroepithelium. As a step toward understanding the mechanisms
      which contribute to the development of a cytokinetically distinct striatal
      compartment, we characterized the rate and pattern of cellular output in the
      lateral ganglionic neuroepithelium of mice on E11. The data show that the
      striatal compartment is distinguished by concurrent and equivalent levels of cell
      output from two proliferative populations: a dominant secondary proliferative
      population and a smaller, pseudostratified ventricular epithelium. In addition,
      although the ganglionic neuroepithelium is expanding on E11, 30-35% of the
      daughter cells produced leave the cell cycle and become postmitotic. These
      cytogenetic events, occurring in the lateral ganglionic progenitor population,
      may contribute to the development of a distinct striatal compartment within the
      telencephalon.

PMID- 9182851
TI  - Calbindin-D28k immunoreactivity in the rat amygdala.
AB  - Calbindin-D28k (CB) is a calcium-binding protein whose exact function has yet to
      be elucidated. Because CB is contained in distinct cell types in the nervous
      system, it is a valuable marker for distinguishing specific nuclear subdivisions
      and neuronal populations. In the present study, immunohistochemical methods were
      used to localize CB in the rat amygdala. A subpopulation of nonpyramidal neurons
      in all nuclei of the basolateral amygdala (ABL) exhibited intense CB
      immunoreactivity (CB-ir). CB-positive puncta resembling axon terminals were
      observed surrounding pyramidal perikarya in the ABL. Pyramidal neurons in caudal
      and lateral portions of the ABL exhibited moderate CB-ir. Intensely stained
      nonpyramidal neurons resembling those of the ABL were also seen in the cortical
      nuclei, periamygdaloid cortex, and nucleus of the lateral olfactory tract; these
      nuclei also contained variable numbers of moderately stained pyramidal cells.
      Numerous CB-positive neurons were observed in all subdivisions of the medial
      nucleus. The posterodorsal subdivision of the medial nucleus exhibited a
      centrally located island of small CB-negative neurons and three cell-dense
      clusters of CB-positive neurons. The distribution of CB-ir in the central nuclear
      complex was very heterogeneous. The intermediate subdivision of the central
      nuclear complex exhibited the most robust staining, whereas the lateral
      subdivision contained relatively few CB-positive cells. Dorsal and ventral
      portions of the lateral capsular subdivision of the central nuclear complex could
      be readily distinguished on the basis of differing levels of CB-ir. These results
      indicate that CB is localized in discrete cell types and nuclear subdivisions in
      the rat amygdala and suggest that CB immunohistochemistry is a useful technique
      for identifying specific structural components in this brain region.

PMID- 9182852
TI  - Optimal ligand binding by the recombinant human glucocorticoid receptor and
      assembly of the receptor complex with heat shock protein 90 correlate with high
      intracellular ATP levels in Spodoptera frugiperda cells.
AB  - The full-length human glucocorticoid receptor (hGR), overexpressed in Spodoptera
      frugiperda (Sf9) cells, associates with heat shock protein 90 (hsp90) and hsp70
      and binds dexamethasone with high affinity. Baculovirus infection of Sf9 cells
      grown in TNM-FH medium results in the rapid depletion of glucose from the medium
      within 24 h. Noting a discrepancy between hGR protein levels and ligand binding
      capacity in such cultures, we hypothesized that the depletion of glucose from the
      medium could result in intracellular ATP depletion and consequently affect the
      ligand binding capacity of the recombinant hGR. Supplementation of the Sf9
      culture medium with additional glucose resulted in a three-fold increase in
      intracellular ATP levels, and a three-fold increase in 3H-dexamethasone binding
      capacity, without altering the protein levels of hGR, hsp90 or hsp70. However,
      more hsp90 co-immunoprecipitated with hGR from cells grown in glucose
      supplemented medium. Our data support the hypothesis that high-affinity ligand
      binding by hGR requires the ATP-dependent formation of the hGR:hsp90
      heterocomplex. Besides having practical consequences for the production of
      recombinant GR and other related proteins, our findings could ultimately have
      relevance in diseases such as diabetes mellitus.

PMID- 9182853
TI  - Characterization of mechanisms of interleukin-6 gene repression by estrogen
      receptor.
AB  - Estrogens are the most effective agents available for preventing osteoporosis,
      and their principal role in bone metabolism is the inhibition of interleukin-6
      (IL-6) production in osteoblasts and bone marrow stromal cells. We examined the
      mechanism of inhibitory effect of estrogens on the 190 bp proximal promoter of
      the IL-6 gene. Promoter activity induced by transfection of both NF-kappaB p65
      subunit and NF-IL6 was decreased by 45% by estradiol (E2)-estrogen receptor (ER)
      complexes. The inhibitory effect of E2 was also observed on a mutant IL-6
      promoter in which the NF-IL6 binding site was disrupted. E2 repressed the wild
      type promoter activity induced by NF-kappaB p65 subunit alone, but had no effect
      on that induced by NF-IL6 alone. These findings suggested that estrogens inhibit
      IL-6 production by interfering with the function of NF-kappaB rather than that of
      NF-IL6. The ER mutant, HE19, which does not contain the A/B domain, repressed the
      induction by NF-kappaB to the same extent as wild-type ER HE0, whereas the effect
      of C-terminal deletion mutant, HE21, was only marginal. The antiestrogen, 4
      hydroxytamoxifen (OHT), had no effect on IL-6 promoter activity, suggesting that
      E2-induced conformational change of the hormone binding domain plays an important
      role in protein-protein interaction between ER and NF-kappaB. E2 had no effect on
      the nuclear translocation of NF-kappaB, and electrophoretic mobility shift assay
      showed that the presence of E2-ER complexes did not affect the ability of NF
      kappaB to bind to specific DNA sequences.

PMID- 9182854
TI  - Sequence of mouse 17beta-hydroxysteroid dehydrogenase type 3 cDNA and tissue
      distribution of the type 1 and type 3 isoform mRNAs.
AB  - The enzyme 17beta-hydroxysteroid dehydrogenase (17betaHSD) interconverts 17
      ketosteroids and 17beta-hydroxysteroids. Five isoforms of the enzyme have been
      identified in the human, two of which (types 1 and 3) have been shown to catalyse
      the reduction reaction preferentially. The cDNA encoding mouse 17betaHSD type 3
      was isolated from testis cDNA using the RACE technique and primers based on the
      human sequence. The mouse protein is 305 amino acids in length which is five
      short of the human protein with four of these amino acids missing at the N
      terminus. The predicted amino acid sequence is 72.5% identical and 94.8% similar
      to the human sequence. Tissue distribution of mRNA encoding both types 1 and 3
      17betaHSD was studied using reverse transcription and the polymerase chain
      reaction (RT-PCR). Highest levels of type 1 mRNA were found in the ovary whereas
      highest levels of type 3 were in the testis. All other tissues tested contained
      mRNA encoding both isoforms of the enzyme although levels were markedly lower
      than in the gonads.

PMID- 9182855
TI  - Expression of estrogen receptor exon 5 splicing variant (ER E5SV) mRNA in
      gynaecological cancers.
AB  - Estrogen receptor exon 5 splicing variant (ER E5SV) mRNA has been found in
      tumours and the corresponding normal tissues, being transcriptionally active
      without ligand binding. Therefore, the expression of ER E5SV mRNA in
      gynaecological cancers was studied. The presence of ER E5SV mRNA was demonstrated
      in the normal ovary, uterine endometrium and cervix and their corresponding
      cancers. The ratio of ER E5SV/ER WT mRNA expression increased in some cases of
      metastatic tumour, but did not decrease in any case. Relative overexpression of
      ER E5SV mRNA might contribute to dominant positive properties and metastatic
      potential. Therefore, detection of ER E5SV mRNA abundance might be a useful
      indicator of metastatic potency in gynaecological cancers.

PMID- 9182856
TI  - DNA bending is induced by binding of the glucocorticoid receptor DNA binding
      domain and progesterone receptors to their response element.
AB  - Circular permutation analysis was used to determine the degree of DNA bending
      induced by binding of the glucocorticoid receptor (GR) DNA binding domain (DBD),
      the human progesterone receptor (PR) DBD, PR-A:A and PR-B:B homodimers, and PR
      A:B heterodimers to the glucocorticoid response element/progesterone response
      element (GRE/PRE). The bending angles induced by the GR DBD and the PR DBD were
      approximately 28 degrees and 25 degrees, respectively. The PR-B:B and PR-A:A
      homodimers and the PR-A:B heterodimers all induced similar DNA bending angles of
      72-77 degrees. The substantially greater DNA bend induced by full-length PR
      compared to the PR DBD indicates that sequences outside the classic zinc finger
      DNA binding domain may play an important role in the interaction of PR with the
      GRE/PRE. Because PR-A:A and PR-B:B homodimers and the PR-A:B heterodimers induce
      similar DNA bends, the different abilities of the PR-A and PR-B isoforms to
      activate transcription are not due to differences in their abilities to distort
      DNA structure.

PMID- 9182857
TI  - Inhibition of mineralocorticoid activity by the beta-isoform of the human
      glucocorticoid receptor.
AB  - Mineralocorticoids and glucocorticoids are important regulators of electrolyte
      homeostasis and arterial blood pressure. Their effects are mediated by the
      mineralocorticoid (MR) and the glucocorticoid receptor (GR), respectively. The
      present study was designed to determine how the two isoforms of the human GR, the
      "classic" GR alpha and the non-hormone-binding GR beta, interfere with the
      transcriptional effects of the hormone-activated human MR. COS-7 monkey kidney
      cells were transfected with different mineralocorticoid-responsive reporter
      plasmids and a vector expressing the human MR protein. Different amounts of
      either control, GR alpha, or GR beta plasmid were co-transfected, and luciferase
      activity was measured after stimulation with aldosterone and/or dexamethasone. MR
      mediated stimulation of transcription was enhanced by co-transfection of the GR
      alpha expression vector. In contrast, MR-mediated stimulation of transcription
      was strongly inhibited by co-transfection of equal amounts of the GR beta
      expression vector. Reverse transcription-polymerase chain reaction (RT-PCR)
      showed expression of both GR isoforms as well as of MR in the human kidney. These
      data indicate that the two isoforms of the human GR exert opposite effects on
      mineralocorticoid activity. We conclude that the ratio between GR alpha and GR
      beta can define the sensitivity of mineralocorticoid target tissues to
      aldosterone. Imbalances of this ratio may participate in clinical syndromes of
      impaired or augmented mineralocorticoid sensitivity, such as certain cases of
      pseudohypoaldosteronism or, possibly, primary arterial hypertension.

PMID- 9182859
TI  - The hydrocortisone-induced transcriptional down-regulation of beta-galactoside
      alpha2,6-sialyltransferase in the small intestine of suckling rats is suppressed
      by mifepristone (RU-38.486).
AB  - The progressive loss of sialic acids of the brush-border membrane glycoproteins
      is one of the major biochemical changes which occur in the rat small intestine
      during the transition from suckling to weaning, and this process is speeded up by
      an injection of glucocorticoids to the suckling animals. We used the rat liver
      beta-galactoside alpha2,6-sialyltransferase (ST6(N), EC 2.4.99.1) cDNA as a probe
      to examine the mRNA level of this enzyme in the small intestine of both suckling
      (13-day-old) and weaned (25-day-old) rats. In the ileum of suckling rats, the
      ST6(N) mRNA level was about four times higher than in the jejunum, whereas the
      membrane-bound enzyme activity was less than two times higher. In comparison with
      the controls, hydrocortisone treatment significantly decreased the level of this
      transcript and of the corresponding enzyme activity in both segments of the small
      intestine of suckling rats. Additionally, the antiglucocorticoid mifepristone (RU
      38.486) suppressed the effect of hydrocortisone. The expression of ST6(N) mRNA in
      the small intestine of weaned (25-day-old) rats was several times lower than that
      in suckling (13-day-old) rats, and was unresponsive to hydrocortisone as well as
      to mifepristone. These results indicate that the glucocorticoid-induced
      transcriptional down-regulation of ST6(N) expression in the small intestine of
      suckling rats is mediated via the glucocorticoid receptor pathway, and support
      the notion that alterations in sialylation of brush-border membrane
      glycoconjugates occurring upon weaning are the result of a lower expression of
      ST6(N).

PMID- 9182858
TI  - Functional dissociation between glucocorticoid-induced decrease in arachidonic
      acid release and inhibition of adrenocorticotropic hormone secretion in AtT-20
      corticotrophs.
AB  - The biochemical basis of the short-term inhibitory effects of glucocorticoids on
      corticotropin release from pituitary corticotrophs is still obscure. A well
      characterized effect of glucocorticoids in several cell types is the inhibition
      of arachidonic acid (AA) generation by phospholipase A2 (PLA2). Arachidonic acid
      and its metabolites have been implicated in the secretory process from a number
      of pituitary cells, such as the corticotrophs. We have thus examined the role of
      AA in the anti-secretagogue effects of glucocorticoids in a corticotropin
      secreting clonal corticotroph line (AtT-20 D16/16). Glucocorticoids decreased AA
      release induced by melittin, a bee venom protein related to extracellular PLA2.
      When a possible role of AA in corticotropin release was studied, the following
      results were obtained: (a) all corticotropin secretagogues tested, including
      corticotropin-releasing factor (CRF), did not alter AA generation; (b) calcium
      and guanine nucleotides, which stimulate corticotropin release in permeabilized
      cells, inhibited the release of AA under the same conditions; (c) administration
      of melittin or of exogenous AA had no effect on basal and CRF-stimulated
      corticotropin release; (d) administration of large amounts of exogenous AA was
      unable to restore the ability to secrete corticotropin under suppression by
      glucocorticoids. Altogether, the data suggest that whereas glucocorticoids can
      inhibit both AA generation and corticotropin release, these two effects appear to
      be causally unrelated.

PMID- 9182860
TI  - Spermatogenesis in the vitamin A-deficient rat: possible interplay between
      retinoic acid receptors, androgen receptor and inhibin alpha-subunit.
AB  - In order to understand the mechanisms of retinol action on the testis, testicular
      retinoic acid receptor alpha, beta(RAR alpha and beta), androgen receptor (AR)
      and inhibin alpha-subunit were studied in normal, vitamin A-deficient (VAD) and
      vitamin A-supplemented rats by immunohistochemistry and immunoblotting. Compared
      to the normal testis, expression of 110 K AR was up-regulated by vitamin A
      withdrawal, whereas 51 K RAR alpha remained unchanged. An additional 55 K RAR
      alpha signal was observed. Readministration of retinol caused a marked decrease
      of AR in the VAD testis. By 24 h, AR declined to below the normal level. Although
      the 51 K RAR alpha signal remained unchanged, the 55 K band was slightly up
      regulated at 6 h after retinol administration. A 51 K RAR beta protein was seen
      in the VAD but in not the normal testis. The intensity of the 51 K RAR beta band
      remained constant before and after the administration of retinol, but it had a
      slight up-shift at 6 h after retinol injection, suggesting post-translational
      modification of the receptor. The inhibin alpha-subunit of 18 K protein was
      undetectable in the VAD testis and increased to above normal level at 24 h after
      retinol administration. Immunohistochemically, nuclear AR immunostaining was more
      intense in the VAD testis than in the normal testis. The intensity of
      immunostaining declined in all AR-positive cells after the injection of retinol,
      but the decrease was more evident in Sertoli than in other cells. At 24 h after
      retinol the immunostaining was undetectable in most Sertoli cells. The regulation
      of the inhibin alpha-subunit by retinol in the cytoplasm of Sertoli cells
      detected by immunohistochemistry was correlated to the results in immunoblotting.
      These results suggest a possible interplay between retinoids, androgen and
      inhibin signalling systems in Sertoli cells in the regulation of spermatogenesis
      during retinol action.

PMID- 9182861
TI  - Direct inhibitions of the activities of steroidogenic cytochrome P-450 mono
      oxygenase systems by anticonvulsants.
AB  - The effects of anticonvulsants on the activities of cytochromes P
      450(17alpha,lyase) (CYP17), P-450arom (CYP19), P-450C21 (CYP21), P-450SCC
      (CYP11A1), and P-450(11beta) (CYP11B1) mono-oxygenase systems were studied using
      rat testicular microsomes, human placental microsomes, bovine adrenocortical
      microsomes, bovine adrenocortical mitochondria and purified cytochrome P
      450(11beta). Phenytoin, clonazepam and carbamazepine inhibited the
      steroidogenesis catalysed by these cytochrome P-450 mono-oxygenase systems and
      the Ki values for each anticonvulsant were determined. Neither hydantoin nor
      sodium valproate inhibited the activities of steroidogenic cytochromes P-450.
      When the activities of cytochromes P-450arom and P-450C21 were measured in the
      presence of anticonvulsants, the Ki values (0.15 mM) for phenytoin were close to
      the plasma concentration of phenytoin under therapeutic conditions. Phenytoin,
      clonazepam and carbamazepine directly inhibited the monooxygenase activities of
      cytochromes P-450, because they did not affect the activities of NADPH-cytochrome
      P-450 reductase, NADPH-adrenoferredoxin reductase and adrenoferredoxin.

PMID- 9182862
TI  - Differentiation induction of HL60 cells by 1,25(OH)2D3, all trans retinoic acid,
      rTGF-beta2 and their combinations.
AB  - 1,25 Dihydroxyvitamin D3 (D3), all trans retinoic acid (atRA) and the cytokine
      rTGF-beta2 are growth and differentiation modulators of promyelocytic leukemia.
      D3 gives rise to a functional monocytic cell population whereas single atRA
      therapy induces granulocytic cell features. rTGF-beta2 reduces HL60 cell
      proliferation but has no differentiating capacity. Combination treatment
      demonstrates additive effects between either D3 and atRA or D3 and rTGF-beta2,
      resulting in a cell population with mixed characteristics since individual cells
      exhibit both monocytic as granulocytic cell features. The capacity of single and
      combined treatments to induce a permanent differentiation was investigated.
      Therefore, cells were preincubated with the drugs during six days, test drugs
      were removed and cell number was monitored. The total cell count of populations
      treated with single agents remains constant for only a few days and then
      increases rapidly. rTGF-beta2 cooperated with D3 in inducing a long-lasting
      differentiation state (3 weeks). Addition of atRA to this combination did not
      significantly alter proliferation or differentiation, but some cells underwent
      apoptosis. Therefore, a total and permanent differentiation of leukemic cells may
      be achieved by repeated exposure to a combination of differentiation inducing
      agents.

PMID- 9182863
TI  - Immunocytochemical localization of C-myc and C-jun oncoproteins in hamster kidney
      and estrogen-induced kidney tumors.
AB  - The chronic administration of 17beta-estradiol to male Syrian hamsters for 6-7
      months induces kidney tumors which express high levels of c-fos, c-myc and c-jun
      mRNA compared to surrounding tissue or untreated controls. In this study, we have
      investigated, by immunocytochemical methods, the cellular localization of c-myc
      and c-jun oncoproteins in estrogen-dependent kidney tumors, in kidney tissue of
      hamsters treated with 17beta-estradiol for 6 months and in the kidneys of age
      matched controls. The c-myc oncoprotein was strongly expressed in tumors, in
      smooth muscle layers of arteries and in parietal epithelial cells of the
      glomerulus. In age-matched untreated kidneys, there was little or no staining in
      the glomerulus, arteries or kidney tubular cells. The c-jun oncoprotein was
      detected in kidney tumors and in the tubular epithelium of surrounding tissue.
      The immunoreactivity for c-jun oncoprotein was highest in the tumor, intermediate
      in estrogen-treated kidney tissue and lowest in kidney tubular cells of controls.
      It is concluded that the high expression of c-myc in estrogen-induced kidney
      tumors, in the smooth muscle layer of arteries, and in glomerular parietal
      epithelial cells in the kidneys of 17beta-estradiol-treated hamsters, but poor
      expression in control kidneys indicate an involvement of this oncoprotein in the
      tumorigenic process. In contrast, c-jun is expressed in untreated, in 17beta
      estradiol-treated kidneys and in tumors, and may not serve as a prognostic marker
      in the transformation of these cells to the malignant phenotype.

PMID- 9182864
TI  - Pseudohypoaldosteronism due to renal and multisystem resistance to
      mineralocorticoids respond differently to carbenoxolone.
AB  - Type I pseudohypoaldosteronism (PHA) is a hereditary syndrome of salt wasting
      resulting from unresponsiveness to mineralocorticoids. PHA is manifested in two
      clinically and genetically distinct forms, affecting either only the kidney or
      multiple target organs of aldosterone. We examined the mineralocorticoid effect
      of carbenoxolone (CBX) in young PHA patients with either renal or multisystem
      resistance to aldosterone to find out whether CBX may help reduce the requirement
      for a high-salt diet. CBX did not show any significant salt-retaining effect in
      two patients with multiple PHA, and did not affect the renin-aldosterone system.
      In contrast, CBX significantly suppressed the renin-aldosterone system in a renal
      PHA patient for the whole duration of treatment, but without a long-term salt
      retaining effect. On CBX treatment, urinary cortisone levels decreased and the
      cortisol:cortisone ratio increased, indicating that CBX inhibited 11beta-HSD
      activity that metabolizes cortisol to cortisone. The complete lack of effect of
      CBX on the renin-aldosterone system in multisystem PHA patients indicates that
      CBX does not exert an effect via mineralocorticoid (MR) or glucocorticoid
      receptors. Examination of the structure and expression of the MR gene by Southern
      blot analysis and polymerase chain reaction (PCR) showed no abnormality. Whereas
      multiple PHA results from a spectrum of mutations in the mineralocorticoid
      activated epithelial sodium channel subunits, the genetic basis of renal PHA is
      still unknown. The response to CBX suggests that there is at least a partly
      functional MR in renal PHA patients.

PMID- 9182865
TI  - The ovarian progestogen receptor in the spotted seatrout, Cynoscion nebulosus,
      demonstrates steroid specificity different from progesterone receptors in other
      vertebrates.
AB  - A nuclear progestogen receptor has previously been characterized in the ovary of
      the spotted seatrout. The steroid specificity of this receptor was further
      defined in the present study by determining the binding affinity of a wide
      variety of progestin and corticosteroid agonists and antagonists. The addition of
      a hydroxyl or keto group to the 11 position resulted in a 10-100-fold decrease in
      relative binding affinity (RBA). The significance of the 17, 20, and 21 positions
      in determining the RBA of closely related steroids was investigated in detail.
      Modification of the 17alpha-hydroxyl to an acetyl or carbyne group resulted in a
      10-fold decrease in RBA. The substitution of a ketone group with a hydroxyl group
      at the 20 position increased binding, whereas the addition of a 21-hydroxyl group
      consistently decreased RBA by 40-60%. The effect of the 17alpha-hydroxyl group on
      RBA was dependent on what functional group was present at the 20 position. The
      addition of a 17alpha-hydroxyl decreased affinity by one- to 10-fold if a ketone
      group was present at position 20. However, the RBA increased five- to 10-fold
      upon addition of the 17alpha-hydroxyl group if a hydroxyl was present at the 20
      position. The effects of the different substitutions at the 17, 20 and 21
      positions explain why the two teleost maturation-inducing steroids 17alpha,20beta
      dihydroxy-4-pregnen-3-one (17alpha,20beta-P) and 17alpha,20beta,21-trihydroxy-4
      pregnen-3-one (20beta-S) have higher affinities than progesterone for this
      receptor. It is concluded that the seatrout progestogen receptor demonstrates
      steroid specificity different from progesterone receptors in other vertebrates.

PMID- 9182866
TI  - 5alpha-reduction of norethisterone enhances its binding affinity for androgen
      receptors but diminishes its androgenic potency.
AB  - Norethisterone (NET), a 19-nor synthetic progestin, undergoes enzyme-mediated
      5alpha-reduction and exerts potent androgenic effects in target organs. To
      investigate its mode of androgenic action we examined, in a comparative manner,
      the in vitro metabolism of NET and testosterone (T), as well as the binding
      affinities to androgen receptors (AR) and the androgenic potency of NET, T, and
      their 5alpha-reduced derivatives. Bioconversion of [3H]-NET and [3H]-T was
      studied in rat prostate homogenates, AR binding affinity was assessed in rat
      ventral prostates using [3H]-mibolerone as the radioligand, and the androgenic
      potency was evaluated by the increase of beta-glucuronidase activity in the mouse
      kidney, and by the growth of accessory sex organs in castrated male rats. The
      results demonstrated that 5alpha-NET displayed a higher AR binding affinity but a
      significantly lower androgenic potency than unchanged NET. The bioconversion
      studies indicated that the metabolism of NET was similar to that of T, although
      to a lesser extent, thus ruling out the possibility that the synthetic progestin
      metabolizes rapidly into less active derivatives. To investigate the nature of
      the paradoxical effect of 5alpha-reduction upon the NET molecule, the interaction
      with AR and the androgenic potency of T, 19-nortestosterone (19norT), 17alpha
      ethynyl testosterone (ET) and their 5alpha-reduced derivatives were examined. The
      results of AR binding studies revealed that 5alpha-reduction of T and ET
      significantly enhanced their affinities, and that the 5alpha-derivative of 19norT
      displayed a similar binding affinity to that exhibited by 19norT. In terms of
      biological activity, the results showed that 5alpha-reduction of T and 19norT
      significantly increased their androgenic potency, whereas 5alpha-reduction of ET
      resulted in a significant diminution of its androgenicity in a manner similar to
      that observed with the 5alpha-reduction of NET. When NET and 19norT were
      simultaneously administered with 5alpha-dihydrotestosterone they exhibited a
      potent synandrogenic activity, an effect that was cancelled by their 5alpha
      reduction. Interestingly, ET displayed an antiandrogenic activity, an effect that
      was also suppressed by its 5alpha-reduction. The overall results demonstrated a
      distinctive, paradoxical effect of 5alpha-reduction upon the NET molecule, which
      was different from that seen in naturally occurring androgens, and which suggests
      that the presence of the 17alpha-ethynyl group plays a key role in this
      phenomenon. The data provided further evidence that the metabolism of synthetic
      contraceptive progestins modulates the expression of their hormone-like actions.

PMID- 9182867
TI  - Non-steroidal L-245,976 acts as a classical antiandrogen in vitro.
AB  - Non-steroidal antiandrogens have been employed in the management of prostate
      cancer, but the mechanism of action is unclear due to a lack of good tissue
      culture models. The growth of a hamster ductus deferens cell line (DDT1) is
      highly dependent upon the addition of 10 nM testosterone to synthetic serum-free
      media. We describe a non-steroidal compound N-(4-chlorophenyl)-(Z,Z)-2,3-bis(
      cyclopropylmethylene) cyclopentanecarboxamide (L-245976) which antagonizes the
      action of testosterone on DDT1 cells at 10 microM but exhibits little or no
      effect on cell growth by itself. This compound also blocks the binding of 3H
      dihydrotestosterone (DHT) to the human androgen receptor (AR) with an IC50 of
      approximately 28 microM. In addition, L-245976 was found to antagonize DHT
      dependent transactivation of the AR via the probasin gene promoter at comparable
      doses with no agonist activity.

PMID- 9182869
TI  - Pregnenolone-7beta-hydroxylating activity of human cytochrome P450-1A1.
AB  - In many human and murine tissues, both pregnenolone and dehydroepiandrosterone
      are hydroxylated at the 7alpha and 7beta positions by a cytochrome P450
      containing microsomal complex. The 7alpha- and 7beta-hydroxysteroids produced
      were shown to activate an immune response in mice. Based upon identification by
      crystallization to constant specific activity and gas chromatography-mass
      spectrometry analysis, we ascertained that a yeast-expressed human cytochrome
      P450-1A1 was able to 7beta-hydroxylate pregnenolone (K(M) from 3.2 +/- 0.5 to 4.1
      +/- 0.4 microM, turnover number from 117 +/- 15 to 135 +/- 13 pmol/min/nmol of
      cytochrome P450-1A1). The other human cytochromes P450 tested did not produce
      identifiable quantities of 7alpha- or 7beta-hydroxylated derivatives of
      pregnenolone or dehydroepiandrosterone. These findings indicate that cytochrome
      P450-1A1 involvement in the 7beta-hydroxylation of pregnenolone may contribute to
      the production of the 7-hydroxylated steroids necessary for activation of the
      immune defences.

PMID- 9182868
TI  - Use of gas chromatographic-mass spectrometric techniques in studies of androst-16
      ene and androgen biosynthesis in human testis; cytosolic specific binding of
      5alpha-androst-16-en-3-one.
AB  - Homogenates of histologically normal human testis from three men were incubated
      separately with pregnenolone, 16-dehydropregnenolone, 5alpha-pregnane-3,20-dione,
      3beta-hydroxy-5alpha-pregnan-20-one and androsta-5,16-dien-3beta-ol
      (androstadienol) in the presence of NADPH in a study of androst-16-ene and
      androgen biosynthesis. After the addition of internal standards and initial
      extraction and purification, metabolites were identified using gas chromatography
      mass spectrometry (GC-MS) and monitoring selectively for three principal ions in
      each case at the appropriate GC retention time. Quantification was achieved by
      comparison with calibration lines for authentic steroids, together with the
      appropriate internal standards, prepared by monitoring three ion fragments for
      each analyte. In all experiments, androstadienol was found to be the major
      androst-16-ene metabolite of pregnenolone (seven times the control, i.e.
      endogenous, quantity; 19.8 +/- 3 ng/100 mg homogenate protein, mean +/- SEM, n =
      9). Pregnenolone was also converted to androsta-4,16-dien-3-one (androstadienone)
      with three times the endogenous quantity (44 +/- 10 ng/100 mg homogenate protein,
      mean +/- SEM, n = 9) being formed. The formation of testosterone occurred only in
      trace amounts in the incubations of testis taken from one man (a 69-yr-old) but
      appreciable yields (six times endogenous levels 90 +/- 7 ng/100 mg homogenate
      protein, mean +/- SEM, n = 9) were found with testes from two younger men. Only
      traces of 5alpha-dihydrotestosterone were detected. Using androstadienol as the
      substrate, androstadienone was shown to be the major metabolite (approximately 10
      times greater than control incubations) together with 5alpha-androst-16-en-3alpha
      and 3beta-ols at approximately twice the endogenous quantities (5 ng/100 mg
      homogenate protein). In some incubations with androstadienol, 5alpha-androst-16
      en-3-one (5alpha-androstenone) was formed (32 +/- 1 ng/100 mg homogenate
      protein/h; mean +/- SEM, n = 3); surprisingly, no endogenous 5alpha-androstenone
      could be detected. No evidence was obtained for the production of testosterone or
      5alpha-DHT from androstadienol. Using cytosolic fractions of human testis,
      specific (displaceable) binding of 5alpha-androstenone was determined, with
      binding sites of approximately 200 fmol/mg tissue and a Ka of approximately 8
      nmol/l.

PMID- 9182870
TI  - Profound effects of the weak environmental estrogen-like chemical bisphenol A on
      the growth of the mammary gland of Noble rats.
AB  - In the present study we have examined the effects of the environmental estrogenic
      chemical bisphenol A on proliferative activity, cell cycle kinetics and
      differentiation of the mammary gland of female Noble rats. Differentiation
      measured by the degree of lobular maturation revealed that the conversion of
      immature structures to mature structures was significantly increased in response
      to exposure to both low (0.1 mg/kg/day) and high (54 mg/kg/day) doses of
      bisphenol A compared to controls. The proliferative activity of epithelial cells
      was increased by 143% over controls by the exposure of animals to the low dose of
      bisphenol A, whereas a 220% increase over controls was observed for the high dose
      of bisphenol A. The labelling index and growth fraction were 19% and 27%,
      respectively, for a low dose of bisphenol A; and 27% and 45%, respectively, for a
      high dose of bisphenol A, compared to 18% and 31%, respectively, in controls. A
      significant increase in the conversion of mammary epithelial cells from G0, to
      G1, and S-phase cells by 1.8 and 4.5-fold, respectively, was observed in animals
      exposed to the high dose of bisphenol A compared to that of controls. Based on
      the previously reported estrogenic activity of an equivalent dose of bisphenol A
      to that of diethylstilbestrol (DES) (0.1 mg/kg/day), a calculated theoretical
      dose of the order of 10(6)-fold higher of bisphenol A will be required to produce
      the same biological effects as DES. A comparison of the proliferative activity of
      DES and that of an equivalent dose of bisphenol A observed in this study,
      however, revealed that its influence on proliferative activity in the epithelial
      cells of the mammary gland was profound. The weak estrogenic activity of
      bisphenol A does not explain its profound effect on cell proliferation observed
      in this study. Perturbation of the cell cycle is considered a risk factor for the
      development of cancer. Bisphenol-mediated perturbation of the cell cycle in
      epithelial cells may produce adverse effects in the mammary glands of Noble rats.

PMID- 9182871
TI  - Sequencing and immunochemical characterization of the American cockroach per a 3
      (Cr-PI) isoallergenic variants.
AB  - Two additional members of the American cockroach (Periplaneta americana) Per a 3
      (Cr-PI) allergen, C13 and C28, were isolated and sequenced. They encoded proteins
      of 470 and 393 amino acids with two and no potential N-glycosylation sites,
      respectively. The molecular weights for C13 and C28 cloned proteins are 56,200
      and 46,7000, with PI values of 7.06 and 6.54. C13 and C28 display 95.4% identity
      with several overlapping predicted central antigenic determinants. Both allergens
      were also found to have a 95% sequence homology with previously cloned C20 and
      share similar antigenic determinants, as defined by the structural prediction and
      ELISA analysis. However, the recombinant C13 and C28 allergens showed 26.3 and
      94.7% skin reactivities on asthmatic patients while C20 elicited 47.4%. While no
      sequence similarity was found to other known allergens, these two aromatic amino
      acid-rich allergens were highly related to insect hemolymph proteins (28.7
      36.5%), as with C20 cloned protein. Results suggest that these two are
      isoallergenic variants of C20. Sequence variations among isoforms, resulting a
      significant difference in skin reactivities, will be useful in elucidating the
      allergenic determinants.

PMID- 9182872
TI  - Isolation of anti-mesothelin antibodies from a phage display library.
AB  - Phage display has been used to select single-chain Fvs (scFvs) against
      mesothelin, a surface antigen present on mesothelial cells as well as
      mesotheliomas and non-mucinous ovarian cancers. Several attempts to produce anti
      mesothelin hybridomas from spleen cells of mice immunized with recombinant
      mesothelin were unsuccessful. This report describes the isolation of anti
      mesothelin scFvs from a phage display library made from the mRNA of the same
      spleens. Panning on recombinant antigen produced in E. coli or on antigen
      positive cells was employed. Several scFvs which bind specifically to mesothelin
      were isolated. Panning on recombinant antigen yielded five different scFvs.
      Panning on cells selected two different scFvs which also differ from the scFvs
      selected by recombinant antigen. The heavy chains of the scFvs selected on
      recombinant antigen are derived from four different heavy chain gene families and
      the scFvs selected on cells are derived from two of these families. In contrast,
      the light chains of all of these scFvs are derived from family XI. Moreover, the
      light chains of the two scFvs selected on cells are very similar to the light
      chains of two of the scFvs selected by panning on recombinant mesothelin except
      for a few point mutations. One of these scFvs which have been studied in detail
      has been shown to bind specifically to mesothelin positive transfected cells.

PMID- 9182873
TI  - Evidence for hapten recognition in receptor-mediated intracellular uptake of a
      hapten-protein conjugate by murine macrophage.
AB  - Fluorescein-derivatized bovine serum albumin (FITC-BSA) was used as an exogenous
      antigen and fluorescent probe to measure the kinetics of antigen uptake into the
      endocytic pathway of murine macrophage, J774, using flow cytometry. Results
      revealed dependency of the rate of antigen uptake on epitope density (moles
      FITC/mole BSA) implicating a role for FITC in the endocytosis of the derivatized
      antigen. In addition, inhibition of clathrin-coated pit formation in macrophage
      resulted in significantly reduced uptake of differentially labeled FITC BSA
      probes indicating receptor-mediated endocytosis via clathrin-coated pits.
      Fluoresceinamine (I) was found to inhibit the endocytic uptake of FITC-BSA at 10(
      6) M. Determination of fractional receptor occupancies in macrophage upon binding
      different FITC BSA probes and calculation of the corresponding association rates
      (k(on)) for these binding events yielded values of 4.2+/-0.2 x 10(6)/M/min for
      FITC5BSA and 1.9+/-0.1 x 10(7)/M/min for FITC22BSA, respectively, at 37 degrees
      C. The five-fold difference in the rates of binding and endocytosis between the
      two probes was discussed on the basis of receptor cross-linking by a multivalent
      ligand (FITC22BSA), in contrast to monovalent ligand binding, on the cell surface
      that would lead to more rapid and efficient internalization of the FITC22BSA
      antigen.

PMID- 9182874
TI  - Binding of complement component Clq to myelin oligodendrocyte glycoprotein: a
      novel mechanism for regulating CNS inflammation.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is a myelin-specific protein restricted
      to the central nervous system (CNS). While MOG is considered a putative
      autoantigen in MS, its function(s) in myelin is unknown. As CNS myelin is able to
      activate the classical complement pathway, it must contain a Clq
      binding/activating protein but the identity of this protein has not been
      reported. The data in this paper clearly demonstrate that MOG specifically binds
      Clq in a dose-dependent and saturating manner. This calcium-dependent interaction
      is mediated by the extracellular immunoglobulin-like domain of MOG. This MOG
      domain contains an amino acid motif similar to the core Clq-binding sequence
      previously identified in IgG antibodies. Purified MOG also inhibited the antibody
      dependent lysis of RBC by complement. Taken together, these results demonstrate
      that MOG binds Clq near the IgG binding site and may be the protein responsible
      for complement activation in myelin. This direct interaction between a myelin
      specific protein and Clq has significant implications for CNS inflammation and
      could be particularly important in demyelinating diseases such as multiple
      sclerosis.

PMID- 9182875
TI  - Induction of anti-polycation antibodies in H-2s mice by immunization with nuclear
      antigens.
AB  - Following administration of certain chemicals (heavy metals or lupus-inducing
      drugs), H-2s mice produce autoantibodies reacting with various nuclear antigens
      such as fibrillarin in the nucleolus and histones in chromatin. In the present
      study, we have immunized A.SW (H-2s) mice and their congenic counterparts A.BY (H
      2b) mice with bovine thymus nuclei in Freund's adjuvant. As was previously
      observed with lupus-prone mice, such active immunization did not elicit
      antinuclear antibodies in any of the experimental groups. Surprisingly, the A.SW
      immunized with nuclei in adjuvant developed high titers of IgG antibodies that
      reacted exclusively with synthetic polycations. We obtained several monoclonal
      IgG antibodies from these mice and verified that these polycation-reactive
      antibodies were not directed against a specific nuclear antigen. The genetic
      analysis of the monoclonal antibodies further confirmed their clonal diversity.
      The mechanisms leading to the appearance of antibodies reactive with highly basic
      molecules in A.SW mice may be related to their predisposition to produce
      autoantibodies to cationic nuclear antigens (fibrillarin, histones) during
      chemically-induced autoimmunity.

PMID- 9182876
TI  - Specific demethylation of the CD4 gene during CD4 T lymphocyte differentiation.
AB  - The expression of CD4 during T cell development is a highly regulated process.
      Numerous regulatory elements have been identified including a promoter, two
      distinct enhancers and a silencer. Here we report a methylation site in the first
      intron of the CD4 gene that is specifically demethylated in cells which have
      previously, or are currently expressing CD4. In addition, this site becomes
      progressively demethylated as T lymphocytes differentiate from double-negative to
      double-positive to CD4 single-positive thymocytes, and finally to CD4 single
      positive peripheral T lymphocytes. This specific and progressive demethylation
      suggests that this site represents another potential control region for the
      regulation of CD4.

PMID- 9182877
TI  - Immunons revisited: binding of multivalent antigens to B cells.
AB  - The T-independent B cell response induced by highly multivalent hapten polymer
      preparations has been studied extensively. The in vitro measured dose-response
      curve tends to be roughly bell-shaped with the peak response occurring at very
      low ligand concentrations, between 0.1-1 ng/ml for a variety of different
      ligands. Furthermore, polymers with more than approximately 10 haptens tend to be
      stimulatory, whereas polymers with fewer than 10 haptens conjugated, tend to be
      inhibitory. These observations have been perplexing when viewed within the
      context of standard theories of receptor ligation by multivalent ligands. We
      present a new analysis of these previous experiments that reconciles the
      differences between theory and experiment. From this theory it is concluded that
      the peak in the observed dose response curve only weakly reflects properties of
      the ligand and the affinity of surface immunoglobulin for the hapten, but depends
      strongly on the density of antigen-specific B cells in the culture. The number of
      responding cells decreases at low ligand concentrations, because cells have to
      share limiting amounts of ligand and not because of the decreasing probability of
      receptors and ligands meeting each other. Our theory leads to the same conclusion
      as made by previous researchers, namely that a minimum number of receptor sites,
      of the order of 10, need to be bound to a single ligand in order to stimulate a B
      cell. While this conclusion was based on the lack of immunogenicity of antigens
      carrying less than a minimum number of haptens, the quantitative results of this
      study, derived from fitting experimental dose response curves obtained with
      highly multivalent antigens, provide evidence for the immunon hypothesis that is
      based upon the degree of receptor aggregation. Our theory also provides
      quantitative agreement with experimental observations on systems, in which both
      stimulatory and non-stimulatory polymers are mixed in the same system.

PMID- 9182879
TI  - Cytochrome P4502D6: understanding an autoantigen.

PMID- 9182878
TI  - Transcriptional regulation of the human polymeric immunoglobulin receptor gene by
      interferon-gamma.
AB  - IgA is transported into external secretions by the polymeric Ig receptor (pIgR).
      Interferon-gamma (IFN-gamma), a major regulator of pIgR expression, has been
      shown to increase pIgR mRNA levels in HT-29 human colon carcinoma cells. To
      determine the molecular mechanisms of pIgR regulation, genomic DNA containing the
      5'-flanking region of the human pIgR gene was isolated and a single start site of
      transcription in human intestinal epithelial cells was identified. Using chimeric
      reporter plasmids containing flanking regions of the pIgR gene, a segment of the
      pIgR promoter which is necessary and sufficient for induction of transcription by
      IFN-gamma in HT-29 cells was identified. Significantly, the pIgR promoter
      contains three motifs homologous to the interferon-stimulated response element
      (ISRE), two in the 5'-flanking region and one in exon 1 of the pIgR gene. The
      upstream ISREs bind nuclear protein(s) which are constitutively expressed by HT
      29 cells, while the exon 1 ISRE binds interferon regulatory factor-1 (IRF-1),
      following stimulation with IFN-gamma. Furthermore, induction of the IRF-1
      promoter by IFN-gamma correlates with induction of the pIgR promoter by IFN
      gamma. It has previously been demonstrated that induction of pIgR mRNA by IFN
      gamma, requires de novo protein synthesis. It is now shown that IRF-1 is not
      detected in nuclear extracts from HT-29 cells stimulated with IFN-gamma in the
      presence of cycloheximide, suggesting that de novo synthesis of IRF-1 is required
      for induction of pIgR transcription by IFN-gamma.

PMID- 9182880
TI  - Accessory cell function of a human colonic epithelial cell line HT-29 for
      bacterial superantigens.
AB  - The expression and up-regulation of cell adhesion molecules on a human colonic
      epithelial cell line HT-29, and the peripheral blood T lymphocyte proliferation
      responses to bacterial superantigens presented by this cell line were
      investigated, compared with peripheral blood monocytes. In HT-29 cells, there was
      constitutive expression of intercellular adhesion molecule-1 (ICAM-1) and
      lymphocyte function-associated antigen-3 (LFA-3) at a low level, but no
      constitutive expression of HLA-DR, LFA-1, B7-1 and B7-2 molecules. After
      stimulation with the supernatants of staphylococcal enterotoxin B (SEB)
      stimulated peripheral blood mononuclear cells for 48 h, there was significant up
      regulation of HLA-DR and ICAM-1 molecules (both > 90% positive). However, this
      stimulation had no effect on the expression of LFA-1, B7-1, B7-2 and LFA-3
      molecules. In the presence of all tested superantigens SEB, toxic shock syndrome
      toxin-1, and streptococcal pyogenic exotoxin A, stimulated HT-29 cells caused
      significant T cell proliferation. When monocytes were used as antigen-presenting
      cells (APC), the MoAbs against HLA-DR, B7-2 and LFA-3 showed a significant
      inhibition of SEB-induced T cell proliferation. Anti-ICAM-1 MoAb had no effect on
      this response. On the other hand, when stimulated HT-29 cells were used as APC,
      the MoAbs against HLA-DR and ICAM-1 significantly inhibited SEB-induced T cell
      proliferation. In contrast to monocytes, anti-B7-2 and anti-LFA-3 had no effect
      on this response. SEB could not induce HT-29 cells to produce IL-8 directly;
      however, SEB significantly induced the stimulated HT-29 cells to produce IL-8 in
      the presence of T cells. Thus these data demonstrate that the products of
      superantigen-stimulated T cell activation can increase the expression of HLA-DR
      and ICAM-1 molecules on HT-29 cells significantly. Stimulated HT-29 cells can
      serve as APC to bacterial superantigens. This response is an HLA-DR- and ICAM-1
      dependent, but B7-2- and LFA-3-independent process, which was different from
      professional APC monocytes.

PMID- 9182881
TI  - Positive and negative associations of distinct HLA-DR2 subtypes with ulcerative
      colitis (UC).
AB  - In UC, as in many other diseases with a suspected autoimmune etiology or
      pathogenesis, an association with certain HLA class II specificities has been
      investigated. In the Japanese, several studies have shown a positive association
      with DR2, but in Caucasian populations the results are conflicting. Therefore we
      undertook a study of HLA class II gene association with UC in a large group of
      white Madrid patients and ethnically matched controls, using molecular biology
      techniques to investigate whether any allelic subspecificity within the HLA-DR2
      group is associated with susceptibility to or protection against UC. Patients
      with ulcerative colitis (n = 107) and 200 controls were typed using molecular,
      DNA-based techniques for HLA-DRB1, DQA1 and DQB1 alleles. Those HLA-DR2+ were
      then specifically typed for the individual alleles within the HLA-DR2 group. We
      observed a positive association with HLA-DR15 (P=0.021) and its subtype DRB1*1501
      (P=0.018). HLA-DRB1*1502 was also increased, although its frequency both in
      patients and controls was very low. When the HLA-DR2+ population was studied, HLA
      DRB1*1601 was significantly decreased in patients (P=0.026). Both HLA-DR3
      (P=0.002) and HLA-DQB1*02 (P=0.001) were also negatively associated with the
      disease, the latter especially with pancolitis. Therefore, HLA class II
      association with UC is complex, and separate alleles confer either susceptibility
      or resistance. Conflicting results with HLA-DR2 appear to be due to the presence
      in this group of both positively associated (HLA-DRB1*1501 and DRB1*1502) and
      negatively associated (HLA-DRB1*1601) subspecificities. Moreover, HLA-DR3 and HLA
      DQB1*02 are associated negatively.

PMID- 9182882
TI  - A new approach to cytochrome CYP2D6 antibody detection in autoimmune hepatitis
      type-2 (AIH-2) and chronic hepatitis C virus (HCV) infection: a sensitive and
      quantitative radioligand assay.
AB  - Antibodies specific for cytochrome CYP2D6, formally known as liver-kidney
      microsome type-1 antibodies (LKM-1), are characteristically found in a subgroup
      of patients presenting autoimmune hepatitis. They are also found in some patients
      with chronic HCV infection. These autoantibodies are usually detected by indirect
      immunofluorescence, immunoblotting and ELISA tests. In an attempt to set up a
      more sensitive detection assay we developed a quantitative immunoprecipitation
      radioligand assay using a 35S-methionine-labelled CYP2D6 antigen obtained by in
      vitro transcription and translation synthesis. All 16 sera from AIH-2 patients
      strongly bound to this CYP2D6 antigen. Two of the nine sera (22%) from AIH-2
      patients that presented only liver cytosol-1 antibodies also bound to CYP2D6. All
      24 sera from HCV patients that were positive for LKM-1 antibodies by indirect
      immunofluorescence were also positive using this CYP2D6 radioligand assay.
      Lastly, all 15 sera from HCV patients negative for LKM-1 antibodies were negative
      by this test. The present results support the view that this quantitative
      radioligand assay is more sensitive than immunoblotting and ELISA CYP2D6 assays,
      and that it could be used in combination with indirect immunofluorescence assay.

PMID- 9182883
TI  - Restricted expression of Fc gammaRIII (CD16) in synovium and dermis: implications
      for tissue targeting in rheumatoid arthritis (RA).
AB  - Interactions between immune complexes and immunoglobulin Fc receptors may
      contribute to inflammation in RA. Previous studies suggested that Fc gammaRIII
      (CD16) may be preferentially expressed in diseased synovial intima. The
      distribution of immunoreactive Fc gammaRIII was examined in normal fetal limb
      tissues, and both normal and selected abnormal samples of adult synovium and
      skin. In fetal limbs at 10-14 weeks gestation Fc gammaRIII was restricted to
      synovial intima. In normal adult synovium Fc gammaRIII was restricted to intimal
      cells. In inflamed synovia differential expression of Fc gammaRIII in the intima
      was less consistent. In both fetal and adult synovium Fc gammaRIII was largely
      restricted to cells expressing CD45 (leucocyte common antigen). Staining for Fc
      gammaRIII was, however, occasionally associated with CD45 intimal cells in fetal
      synovium. In both fetal and adult tissues cell membrane Fc gammaRIII was
      frequently closely associated with complement decay-accelerating factor (DAF),
      which is present on intimal fibroblasts and extracellular matrix. Fc gammaRIII
      expression was minimal in normal forearm dermis, but widespread on CD45+ cells in
      skin exposed to mechanical stress. In skin containing rheumatoid nodules, Fc
      gammaRIII was preferentially expressed on palisading macrophages. These
      observations indicate that expression of Fc gammaRIII on macrophages may be
      involved in the susceptibility of connective tissues to immune complex-induced
      damage in RA. Colocalization of Fc gammaRIII and DAF in synovium may indicate an
      unrecognized functional interrelationship.

PMID- 9182884
TI  - Expression of molecules involved in B lymphocyte survival and differentiation by
      synovial fibroblasts.
AB  - The synovitis of rheumatoid arthritis (RA) is one of few pathological lesions in
      which B lymphocyte accumulation progresses to the extent of germinal centre
      formation. The present study was designed to assess the ability of synovial
      fibroblasts to express molecules implicated in B lymphocyte survival and
      differentiation, both in vivo, and in response to cytokines in vitro. Normal and
      diseased synovia were examined by indirect immunofluorescence. In all tissues
      synovial intimal fibroblasts showed co-expression of vascular cell adhesion
      molecule-1 (VCAM-1) and complement decay-accelerating factor (DAF) comparable to
      that of follicular dendritic cells (FDC), but not complement receptor 2 (CR2). In
      rheumatoid synovia, subintimal cells showed variable expression of VCAM-1 and
      DAF, with bright co-expression of VCAM-1, DAF and CR2 in lymphoid follicle
      centres. B lymphocytes, some of which were proliferating cell nuclear antigen
      positive, were present in contact with subintimal cells expressing VCAM-1 with or
      without DAF or CR2. B lymphocytes were rarely present in the intimal layer, and,
      where present, showed fragmentation. In vitro, synovial fibroblasts exposed to
      tumour necrosis factor-alpha (TNF-alpha) in combination with interferon-gamma
      (IFN-gamma) showed enhanced expression of VCAM-1, in comparison with fibroblasts
      from skin and lung and, unlike skin and lung fibroblasts, also expressed DAF and
      CR2. These findings support the hypothesis that synovial targeting in RA involves
      an enhanced ability of synovial fibroblasts to support B lymphocyte survival.
      This appears to be dependent, not on the constitutive expression of VCAM-1 and
      DAF on intimal cells, but on the increased ability of subintimal cells to respond
      to proinflammatory cytokines, perhaps critically in the expression of VCAM-1.

PMID- 9182885
TI  - Amelioration of collagen II-induced arthritis in rats by the type IV
      phosphodiesterase inhibitor Rolipram.
AB  - The effect of Rolipram, a selective inhibitor of the cyclic AMP specific
      phosphodiesterase (PDE IV) was evaluated in the rat collagen type II (RCII)
      induced arthritis model in the DA rat. Rolipram was given either shortly before
      expected onset of disease (days 10-14) or shortly after the onset of clinically
      evident arthritis (days 15-19 after immunization). Administration at days 10-14
      delayed the onset of arthritis for approximately 5 days, but the severity of
      arthritis was thereafter comparable to that seen in a non-treated control group.
      Rolipram treatment of animals with manifest arthritis inhibited further arthritis
      development and also tended to diminish its severity at a phase of disease where
      non-treated control animals showed a rapidly progressing disease development.
      Serum levels of antibodies to RCII were in all experiments similar between
      Rolipram-treated and control animals. An in situ hybridization method for
      determining cytokine mRNA synthesis in regional lymph nodes, after administration
      of Rolipram (at days 2-7), demonstrated a strong inhibitory effect on tumour
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNA
      expression, whereas no effects were seen on IL-2 mRNA synthesis after in vivo
      challenge with native RCII emulsified in Freund's incomplete adjuvant. The
      results thus demonstrate strong preventive as well as therapeutic effects of
      Rolipram in a model for arthritis that is very similar to human rheumatoid
      arthritis with respect to cytokine regulation, and suggest that Rolipram has its
      major effects in the effector stage of the arthritogenic immune response.

PMID- 9182886
TI  - A cross-reactive idiotype in scleroderma.
AB  - Autoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are
      highly specific for scleroderma. Unlike most autoantibodies in other diseases,
      these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids)
      expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma
      patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two
      scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids
      were used to study the purified autoantibodies from 20 scleroderma patients: four
      antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma
      patients who were negative for both autoantibodies. In addition, we studied sera
      from 40 normal autoantibody-negative controls, and sera and purified
      immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing
      high titres of anti-double-stranded DNA, and/or autoantibodies to extractable
      nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs
      and immunoblots, we identified an Id present in the heavy chains of all the
      affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id
      was also present in the immunoglobulins of the scleroderma patients who had
      neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not
      found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40
      normal subjects. Several samples from two patients showed that this cross
      reactive Id-EM was stable over time. The scleroderma disease-specific
      autoantibodies may be identified through a common structural feature at the
      variable region of the heavy chain: cross-reactive Id-EM.

PMID- 9182887
TI  - Thalidomide therapy of established collagen-induced arthritis (CIA) not
      accompanied by an evident Th2 shift.
AB  - Thalidomide, a drug likely to affect the cytokine pattern, was administered
      orally to mice at various stages of CIA. Treatment (150 mg/kg per day by gavage,
      5 days/week), started 6 weeks post-immunization, i.e. at the height of the
      disease, significantly reduced arthritis, and appeared also to reduce the level
      of inflammation as judged by neutrophil chemiluminescence. With treatment started
      9 weeks post-immunization the effect on arthritis was no longer statistically
      significant, and when started at 14 weeks was lost. Over a dose range of up to
      150 mg/kg per day the treatment had no effect on either interferon-gamma (IFN
      gamma) or IL-4 mRNA levels. The treatment is therefore not likely to have
      operated via a shift in the Th1/Th2 balance.

PMID- 9182888
TI  - The priming action of tumour necrosis factor-alpha (TNF-alpha) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) on neutrophils activated by
      inflammatory microcrystals.
AB  - We studied the effects of TNF-alpha or GM-CSF on the production of reactive
      oxygen species (as measured by chemiluminescence) and degranulation responses of
      neutrophils to opsonized inflammatory microcrystals. TNF-alpha in the 10-2000 pM
      or GM-CSF in the 2-200 pM concentration range caused the concentration-dependent
      amplification of neutrophil chemiluminescence responses to both calcium
      pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate (MSUM) crystals.
      Degranulation responses, as measured by the extracellular release of the granule
      enzymes myeloperoxidase or lysozyme, were amplified by approximately 50-100% for
      both MSUM or CPPD crystal-induced neutrophil activation when cells were
      pretreated with TNF-alpha at 2000 pM or GM-CSF at 75 pM.

PMID- 9182889
TI  - Gold and D-penicillamine induce vasculitis and up-regulate mRNA for IL-4 in the
      Brown Norway rat: support for a role for Th2 cell activity.
AB  - D-penicillamine (DP) and gold salts which are used as immune-modulating agents in
      the treatment of rheumatoid arthritis are known to be capable of causing
      autoimmune manifestations. Most autoimmune diseases in man are dominated by Th1
      type responses, and one might presume that effective immunotherapy counteracts Th
      activity, perhaps by causing a shift to a Th2 response. The mechanism of action
      of gold and DP is not clear, but some clues may be obtained from their effects in
      animal models. DP, gold salts and mercuric chloride (HgCl2) are known to induce
      Th2-dominated autoimmune syndromes in genetically susceptible rodent strains, and
      we have demonstrated recently that HgCl2 up-regulates messenger RNA (mRNA) for IL
      4 in the Brown Norway (BN) rat. In the BN rat HgCl2 treatment is also associated
      with the development of vasculitis, and anti-myeloperoxidase (MPO) antibodies are
      found in the serum. The present study examined and confirmed the hypothesis that,
      since gold and DP induce an autoimmune syndrome similar to HgCl2 in the BN rat,
      they may also induce vasculitis and an up-regulation in mRNA for IL-4. Tissue
      injury was assessed macroscopically and histologically on day 5 and day 15 after
      the start of injections with gold, DP or HgCl2, serum titres of IgE and presence
      of anti-MPO antibodies were determined using ELISA, and a semi-quantitative assay
      using reverse transcription-polymerase chain reaction was used to assay the level
      of mRNA for IL-4 in spleen and caecum. The relative degree of tissue injury
      reflected the potency of induction of IgE by the three agents (HgCl2 being most
      potent and DP least potent). The lesions were identical histologically,
      supporting the premise that the vasculitis is a manifestation of the autoimmune
      syndrome rather than non-specific HgCl2 toxicity. Both gold and DP induced less
      up-regulation of mRNA for IL-4 than HgCl2. HgCl2 (but not gold or DP) induced
      anti-MPO antibodies. It would be interesting to examine patients treated with
      gold and DP to see if there is evidence of a Th2-type response in those
      developing autoimmune complications, and whether or not the bias to a Th2
      environment contributes to efficacy of treatment of the underlying disease.

PMID- 9182890
TI  - Circulating soluble selectins in Kawasaki disease.
AB  - To investigate the significance of circulating adhesion molecules associated with
      leucocyte-endothelial cell interaction in Kawasaki disease (KD), serum levels of
      soluble E-, P-, L-selectin (sE-, sP-, sL-selectin), and vascular cell adhesion
      molecule-1 (VCAM-1) were measured in 16 patients with KD, eight with other
      febrile diseases, six with Henoch-Schonlein purpura (HSP), and 10 healthy
      children using an ELISA. Serum sE-selectin levels from patients in the acute
      phase of KD were significantly higher than from those in other groups (P < 0.01).
      The levels of sP-selectin in the subacute phase of KD were significantly higher
      than in other groups (P < 0.01). Serum sL-selectin levels tended to rise in the
      convalescent phase of KD. There were also significant correlations between sE
      selectin levels and C-reactive protein (r = 0.80, P < 0.0001), and between sP
      selectin levels and platelet counts (r = 0.57, P < 0.0001) in KD patients. These
      data indicate that circulating soluble forms of three selectins may have
      different kinetics during the clinical course of KD, suggesting that they may
      reflect its inflammatory process.

PMID- 9182891
TI  - Oral administration of antibodies as prophylaxis and therapy in Campylobacter
      jejuni-infected chickens.
AB  - Passive immunity against gastrointestinal infections has recently been
      successfully applied as prophylaxis and therapy in patients in a variety of
      virally and bacterially induced infections. Campylobacter jejuni is frequently
      associated with acute diarrhoea in humans, and several species of animals have
      been shown to transmit the disease, although birds have been implicated as the
      main source of infection. We used bovine and chicken immunoglobulin preparations
      from the milk and eggs, respectively, of immunized animals for prophylactic and
      therapeutic treatment of chickens infected with C. jejuni. A marked prophylactic
      effect (a >99% decrease in the number of bacteria) was noted using either
      antibody preparation, whereas the therapeutic efficacy, i.e. when antibodies were
      given after the infection was established, was distinctly lower (80-95%) as
      judged by faecal bacterial counts. These observations may serve as a starting
      point for experiments aimed at elimination of the infection in an industrial or
      farm setting. It may also encourage future attempts to treat, prophylactically or
      therapeutically, patients with Campylobacter-induced diarrhoea.

PMID- 9182892
TI  - Persistent production of interferon-gamma (IFN-gamma) and IL-12 is essential for
      the generation of protective immunity against Listeria monocytogenes.
AB  - IFN-gamma and IL-12 are believed to be important in the host defence against
      Listeria infection in mice. However, the relationship between these two cytokines
      and generation of protective immunity remains poorly understood. In the present
      study, it was found that at least 4 days of immunizing infection were required
      for the generation of protective immunity against L. monocytogenes. Protective
      immunity was generated only by immunizing infection with virulent strain. Even
      repeated injections of avirulent strain failed to induce protective immunity.
      When the immunizing infection was terminated with antibiotics, generation of
      protective immunity and IFN-gamma-producing ability was impaired, while
      expression of IFN-gamma and IL-12 was also impaired. The mutual relationship
      between IFN-gamma and IL-12 in L. monocytogenes infection was analysed in vitro.
      After neutralization of IL-12, IFN-gamma production was completely blocked and
      IFN-gamma expression was also inhibited. In contrast, there was no change of IL
      12 expression after neutralization of IFN-gamma. Taking all facts into
      consideration, it may be concluded that persistent production of IFN-gamma
      induced by persistent production of IL-12 during immunizing infection is
      essential for the generation of protective immunity against L. monocytogenes.

PMID- 9182894
TI  - Premature removal of uninfected erythrocytes during malarial infection of normal
      and immunodeficient mice.
AB  - Anaemia during blood-stage plasmodial infections is known to be due to at least
      three mechanisms: direct destruction of erythrocytes by the intra-erythrocytic
      parasite, inhibition of erythropoiesis, and premature removal of uninfected
      erythrocytes. The removal of the uninfected erythrocytes is considered by many to
      be dependent on an antibody-mediated mechanism. Our investigations involving
      normal, severe combined immunodeficient (SCID) and nude BALB/c mice and the
      murine malaria parasite Plasmodium yoelii, indicate that this mechanism is
      unlikely. The process of removal of uninfected erythrocytes was reduced in SCID
      mice but could not be enhanced by the passive transfer of serum from infected
      immunocompetent mice. Macrophage activation, as judged by the removal of
      xenogeneic erythrocytes, did not differ in the three strains of mice. Changes in
      the erythrocytes themselves may be responsible for their shortened lifespan.

PMID- 9182893
TI  - A non-protective T helper 1 response against the intra-macrophage protozoan
      Theileria annulata.
AB  - Theileria annulata is a protozoan parasite which infects and transforms bovine
      macrophages. Infected macrophages possess augmented antigen presentation
      capabilities, as they are able to activate the majority of T cells from unexposed
      animals. In vivo, T cells in the draining lymph node (principal site of parasite
      development) are activated 'non-specifically' by the parasite. This event is
      followed by failure of the immune response to control the infection. Protective
      immune responses against intra-macrophage protozoa are usually mediated by T
      helper 1 (Th1) T cell responses. Here we examine the cytokine responses made by
      T. annulata-activated T cells. We show that the outcome of in vitro activation of
      T cells by parasitized macrophages is a skewing of their cytokine responses
      towards preferential expression of interferon-gamma (IFN-gamma) mRNA. The in
      vitro response is mirrored during in vivo infection, as greatly elevated amounts
      of IFN-gamma protein are found in lymph efferent from infected lymph nodes, while
      expression of IL-4 mRNA within the node stops. IFN-gamma production does not
      correlate with protection against the parasite, as infected cells flourish during
      peak IFN-gamma production, and only very small amounts of IFN-gamma are produced
      during the effective immune response of an immunized animal. Overproduction of
      IFN-gamma and loss of IL-4 expression are also likely to account for the failure
      of B cells to reach the light zone of germinal centres, a developmental step
      which is tightly regulated by cytokines.

PMID- 9182895
TI  - Age-related changes in serum immunoglobulins in patients with familial IgA
      deficiency and common variable immunodeficiency (CVID).
AB  - The concentration of serum immunoglobulins in individuals with IgA deficiency
      (IgAD) and CVID can vary with age to have practical implications for evaluation,
      therapy, and genetic analysis. Most IgAD and CVID patients in our clinic
      population in the Southeastern United States have inherited part or all of two
      extended MHC haplotypes, referred to as haplotype 1 (HLA-DQB1 0201, HLA-DR3, C4B
      Sf, C4A-0, G1-15, Bf-0.4, C2-a, HSP-7.5, TNF alpha-5, HLA-B8, HLA-A1) and
      haplotype 2 (HLA-DQB1 0201, HLA-DR-7, C4B-S, C4A-L, G11-4.5, Bf-0.6, C2-b, HSP-9,
      TNF alpha-9, HLA-B44, HLA-A29). In the present study, the clinic records of 68
      CVID patients and 73 IgAD patients were reviewed to determine whether patients
      with familial or MHC-associated IgAD or CVID experience changes in serum
      immunoglobulin concentrations. An increase in serum immunoglobulin to the normal
      range was associated with clinical improvement in one patient with CVID and
      haplotype 2, two patients with IgAD and haplotype 2, and one IgAD patient whose
      haplotype was not determined. Two patients with haplotype 1 and one with
      haplotype 2 had a significant decline in serum immunoglobulin: one progressed
      from normal to IgAD associated with IgG subclass deficiencies, and two progressed
      from IgAD to CVID. Five of the seven patients with notable changing serum
      immunoglobulin levels have a family member with either IgAD or CVID. The findings
      suggest that familial, MHC-associated IgAD and CVID may be either progressive or
      reversible disorders, and emphasize the value of monitoring immunoglobulin levels
      in affected individuals and their family members.

PMID- 9182896
TI  - Combined immunodeficiency phenotype associated with inappropriate spontaneous and
      activation-induced apoptosis.
AB  - Programmed death of T cells has been proposed as one of the mechanisms by which
      HIV induces a decline in the number and functions of T cells in advanced AIDS. In
      this study we report on a patient affected by a congenital form of combined
      immunodeficiency presenting as a profound T cell activation deficiency.
      Subsequently, a gradual loss of T cells occurred, eventually resulting in a
      classical form of severe combined immunodeficiency (SCID). In this patient a
      sizeable fraction of apoptotic cells was documented in the first phase of the
      disease by either propidium iodide staining or DNA fragmentation analysis. The
      presence of anergic T cells of maternal origin and engrafted in the child was
      excluded by analysis of DNA polymorphic regions. At 4 years of age the patient
      died of disseminated interstitial pneumopathy, while still awaiting an HLA
      matched bone marrow transplantation. On the occasion of a new pregnancy in the
      mother, the prenatal immunological evaluation of the female fetus revealed a T B+
      SCID phenotype. This is the first observation of a primary immunodeficiency
      associated with inappropriate apoptosis.

PMID- 9182898
TI  - Heterozygous C8beta complement deficiency does not predispose to meningococcal
      disease.
AB  - We have identified 42 Russian patients with homozygous C8beta complement
      component deficiency, all of whom had experienced at least one episode of
      systemic meningococcal disease. About 90% of these individuals have a C --> T
      exchange in exon 9, leading to a premature stop codon. If, like the homozygous
      deficient state, heterozygous C8beta deficiency constitutes a risk factor for
      meningococcal disease, it would be expected to be detected with increased
      frequency among individuals suffering from this disease. Using allele-specific
      polymerase chain reaction (PCR), we studied 153 consecutive patients with
      meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to
      determine the frequency of C8 null allele. No individuals with heterozygous C -->
      T exchange were identified among these 153 patients, despite the fact that seven
      persons were detected who had homozygous C8beta deficiency, caused by the same C 
      -> T exchange in exon 9, and one patient who had C7 component deficiency. Thus,
      heterozygous deficiency, although more frequent than homozygous deficiency in the
      general population, does not result in a substantial increase in susceptibility
      to meningococcal disease.

PMID- 9182897
TI  - Differential susceptibility to Mycoplasma pulmonis intranasal infection in X
      linked immunodeficient (xid), severe combined immunodeficient (scid), and
      immunocompetent mice.
AB  - Mice with the scid mutation are highly susceptible to Mycoplasma pulmonis
      infection and develop a disseminated disease. In order to study the contribution
      of humoral immunity to the immune response, M. pulmonis was inoculated
      intranasally to X-linked immunodeficient (xid) mice. Severe combined
      immunodeficient (scid) and immunocompetent CBA mice were used as controls. The
      mice were killed and necropsied at day 30 or 37 post-infection. Samples from the
      nose, lungs and joints were taken for bacteriological and histological
      examination. Rhinitis was observed in all mouse strains. Chronic purulent
      bronchopneumonia was diagnosed in some of the CBA mice. Xid mice did not show
      severe lung lesions, despite the presence of numerous mycoplasma organisms in the
      lungs, in contrast to immunocompetent mice, which developed lung pathology. Scid
      mice showed less signs of pneumonia, but unlike in xid and CBA mice, there was
      spread of mycoplasmas from the respiratory tract and severe pathological changes
      in the joints. Our results indicate that B and/or T lymphocytes protect against
      dissemination of M. pulmonis from the airways. Innate immune reactions and/or
      bacterial virulence factors seem to contribute to the development of joint
      lesions, whereas IgG3 and IgM antibodies might be involved in lung pathology.

PMID- 9182899
TI  - Difficulties in the ascertainment of C9 deficiency: lessons to be drawn from a
      compound heterozygote C9-deficient subject.
AB  - A group of patients with long-surviving mismatched kidney allografts were
      investigated for complement function using haemolytic assays in agarose gels. One
      patient was found to have no alternative pathway activity but a low normal
      classical pathway. Surprisingly, investigation revealed that the patient's
      complement was normal for all components except C9, which was functionally
      absent. The patient was shown to be heterozygous for DNA markers in the C6, C7
      and C9 region of chromosome 5 and therefore appears to be a compound heterozygote
      for two uncharacterized C9 deficiency genes. Serological analysis by ELISA
      revealed that he has trace concentrations of a non-functional C9 molecule.
      Western blot analysis was not sufficiently sensitive to permit detection of this
      molecule. We hypothesize that the patient is heterozygous for a complete
      deficiency of C9 and for a gene directing hyposynthesis of a defective C9. We
      also suggest that C9 deficiency may be more common among Caucasians than has been
      reported.

PMID- 9182900
TI  - Effect of body weight and caloric restriction on serum complement proteins,
      including Factor D/adipsin: studies in anorexia nervosa and obesity.
AB  - Complement plays important roles in host immune defences, and recent studies
      suggest that adipose tissue is an important site of production for some
      complement proteins. Starvation has been associated with low complement levels,
      but studied populations have usually had concomitant opportunistic infections or
      other conditions which might affect complement levels. To determine the impact of
      body weight and changes in body weight on serum complement, we investigated
      levels of complement proteins in otherwise healthy patients with a wide range of
      body weights, including patients with anorexia nervosa before and after
      treatment, obese dieters before and after weight loss, and normal weight
      controls. We found that complement proteins of the alternative pathway (C3, B,
      and D), alternative pathway haemolytic activity (AP50) and the inhibitors H and I
      were low in starving anorectics and normalized with weight gain. C3a levels were
      comparable in anorectics at low weight and after weight gain, indicating that low
      serum complement levels were attributable to hypoproduction and not complement
      cascade activation with consumption. Further, levels of C3, B, AP50, H and I, but
      not D, were higher than controls in obese patients and decreased toward normal
      after weight loss. Overall, percentage of ideal body weight, changes in body
      weight, and serum transferrin were each highly correlated with serum levels of
      complement proteins. We conclude that levels of alternative pathway complement
      components are determined in part by factors that influence body weight and by
      weight changes, possibly due to changes in production in adipose tissue or at
      other sites.

PMID- 9182901
TI  - Th1-like responses to peptides from peripheral nerve myelin proteins in patients
      with polyneuropathy associated with monoclonal gammopathy.
AB  - Polyneuropathy associated with monoclonal gammopathy is usually regarded as an
      immune-mediated disorder with autoantibody activity against myelin glycoproteins.
      The pathogenic mechanisms are, however, not fully understood. Several reports
      have indicated an additional involvement of T cells. We investigated the
      occurrence of myelin-specific T cells as well as their functional
      characteristics. Cytokine responses generated after stimulation of peripheral
      blood mononuclear cells with selected peptides of myelin proteins P0 and P2 were
      investigated with an ELISPOT method. Three P0 peptides caused significantly
      elevated levels of interferon-gamma (IFN-gamma)-secreting cells in patients with
      polyneuropathy associated with monoclonal gammopathy (n = 8) compared with
      controls (n = 8), whereas none of the peptides caused elevated levels of IL-4
      secreting cells. Patients with non-immunological types of neuropathy (n = 4) did
      not reveal any cytokine responses to myelin peptides. Our results indicate that a
      Th1-like response against myelin proteins occurs in polyneuropathy associated
      with monoclonal gammopathy.

PMID- 9182902
TI  - Cellular mRNA expression of interferon-gamma (IFN-gamma), IL-4 and IL-10 relates
      to resistance to experimental autoimmune myasthenia gravis (EAMG) in young Lewis
      rats.
AB  - Age-related alterations in the immune system, including changes in lymphocyte
      subset composition, result in changes of cytokine patterns and might thereby
      influence the incidence and severity of autoimmune diseases. To investigate the
      age-related resistance to EAMG, an animal model for human MG, young (4-week-old)
      and adult (8-10-week-old) female Lewis rats were immunized with Torpedo
      acetylcholine receptor (AChR) and Freund's complete adjuvant (FCA). Adult Lewis
      rats showed severe weight loss and progressive muscular weakness after
      immunization, while young rats developed minor clinical signs of EAMG after a
      prolonged interval post-immunization. By comparison with adult rats, the young
      had lower AChR-specific T and B cells responses, and less muscle AChR loss. In
      situ hybridization performed on mononuclear cells (MNC) from lymph nodes revealed
      that young rats had lower levels of AChR-specific IFN-gamma, IL-4 and IL-10 mRNA
      expressing cells compared with adult rats. Since IFN-gamma, IL-4 and IL-10
      promote the development of EAMG, the low expression of these cytokines might
      contribute to EAMG resistance in young Lewis rats.

PMID- 9182903
TI  - Non-restricted T cell receptor (TCR)-V alpha and -V beta gene usage in patients
      with pulmonary sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized
      by the pronounced accumulation of CD4+ T cells and macrophages in the affected
      organs. TCR variable (V) alpha and V beta gene usage in patients with sarcoidosis
      is still a matter of discussion. In this investigation, we analysed TCR-V alpha
      and -V beta gene usage in bronchoalveolar lavage fluid (BALF) and peripheral
      blood mononuclear cells (PBMC) of 30 patients with active pulmonary sarcoidosis
      using an adapter ligation method, reverse transcriptase-polymerase chain reaction
      (RT-PCR), and sequence-specific oligonucleotide probe (SSOP) analyses. There was
      no significant difference in TCR-V alpha or -V beta gene usage between BALF (n =
      12) or PBMC (n = 27) of patients and PBMC of healthy subjects (n = 10). Neither
      selective TCR-V alpha nor -V beta expansion was observed in the paired BALF and
      PBMC from seven of nine patients. However, selective expansions were observed in
      a few TCR-V alpha or -V beta subsets in the BALF or PBMC of some individuals.
      Although a modest increase in a few TCR-V alpha or -V beta subsets was observed
      in the BALF or PBMC of some individuals, the increased TCR-V alpha or -V beta
      subsets were not closely associated with the HLA-DRB1, DQA1, DQB1, and DPB1
      alleles of these patients. These results suggest that TCR-V alpha or -V beta gene
      usage is not restricted in both lung and peripheral blood in the majority of
      patients with active pulmonary sarcoidosis.

PMID- 9182904
TI  - Immunomodulatory effects of linomide in animals immunized with immunopathogenic
      retinal antigens: dissociation between different immune functions.
AB  - Linomide (LS-2616, quinoline-3-carboxamide) has been reported to exert a diverse
      range of effects on the immune system. On one hand, this drug was found to
      stimulate the immune system and to enhance activities such as DTH or allograft
      rejection. On the other hand, linomide was shown to inhibit the induction of
      experimental autoimmune encephalomyelitis and myasthenia gravis, as well as the
      development of diabetes in non-obese diabetic (NOD) mice. Here we report the
      effects of linomide in animals immunized with uveitogenic retinal antigens.
      Treatment with linomide completely inhibited the development of experimental
      autoimmune uveoretinitis (EAU) in mice immunized with interphotoreceptor retinoid
      binding protein and markedly suppressed EAU in rats immunized with S-antigen (S
      Ag). In addition, linomide-treated rats exhibited reduced antibody production and
      lymphocyte proliferative response to S-Ag. In contrast to these suppressive
      activities, linomide treatment did not affect the development of adoptively
      transferred EAU in rats and moderately enhanced the DTH reactions to S-Ag in
      immunized rats in which EAU and other immune responses to this antigen were
      suppressed.

PMID- 9182905
TI  - Different modulation by histamine of IL-4 and interferon-gamma (IFN-gamma)
      release according to the phenotype of human Th0, Th1 and Th2 clones.
AB  - Histamine, an important inflammatory mediator in allergic diseases and asthma,
      has been reported to have modulator effects on T cells, suggesting that the
      bronchial microenvironment may regulate the function of resident T cells. We
      examined the effect of histamine on the release of the Th2-associated cytokines
      IL-4 and IL-5 and the Th1-associated cytokine IFN-gamma by 30 CD4+ T cell clones
      from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL
      4/IFN-gamma ratio, the clones were ascribed to the Th2 (ratio > 1), Th0 (ratio >
      or = 0.1 and < or = 1) or Th1 (ratio < 0.1) phenotype. Histamine inhibited IFN
      gamma production by Th1-like cells (P < 0.02, Kruskall-Wallis), especially from
      bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones,
      histamine inhibited IL-4 production (P < 0.02) in a dose-dependent manner and
      slightly inhibited IFN-gamma production, but had no effect on Th2-like cells.
      Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2
      receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN
      gamma production, whereas the agonist dimaprit mimicked this effect. In contrast,
      H1- and H3-receptor agonists and antagonists had no significant effect. These
      data demonstrate that histamine has different effects on IL-4 and IFN-gamma
      release by T helper cells according to their phenotype via H2-receptors. This
      study extends the immunomodulatory effects of histamine which may contribute to
      the perpetuation of airway inflammation in asthma.

PMID- 9182906
TI  - Jak3 activation in human lymphocyte precursor cells.
AB  - Although expression of the Jak3 tyrosine kinase in T lymphocytes has been thought
      to be restricted to mature, activated cells, mutations of Jak3 can lead to the
      development of a human severe combined immunodeficiency (SCID) characterized by
      an absence of peripheral T lymphocytes. We therefore examined in detail the
      expression of Jak3 throughout human T cell differentiation and show that Jak3 is
      in fact present throughout the entire developmental process, with high levels
      expressed in thymocytes. Jak3 is highly expressed in double negative (CD4- CD8-)
      cells, one of the earliest stages of thymocyte differentiation, and can be
      activated via the IL-7 receptor. IL-7 is known to stimulate thymocyte
      proliferation and initiate re-arrangement of the T cell receptor (TCR) beta gene,
      suggesting that the failure of mutated Jak3 proteins to transduce this signal may
      be responsible for failures in T cell development. While Jak3 SCID patients
      possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase
      is also expressed in human pre-B cells and can be activated by the pre-B cell
      growth factor IL-7.

PMID- 9182907
TI  - Normal CD5+ B lymphocytes are poor stimulators in the autologous mixed lymphocyte
      reaction (AMLR).
AB  - The AMLR is decreased in chronic lymphocytic leukaemia (CLL), which is
      characterized by a monoclonal expansion of CD5+ B lymphocytes. Since B cells are
      used to stimulate the AMLR, we investigated the capacity of normal CD5+ B cells
      to function as stimulators in the AMLR. We isolated B cells from the peripheral
      blood of normal individuals and fractionated them into subpopulations enriched
      for CD5+ and CD5- cells, which were used as stimulators in the AMLR. We found
      that the CD5- B cells were excellent stimulators, whereas stimulation of AMLR by
      B cells enriched for CD5+ cells resulted in significantly reduced proliferative
      responses (P < 0.005). This suggests that the reduced AMLR in CLL is due to the
      predominance of CD5+ B lymphocytes in the stimulating cell population.

PMID- 9182908
TI  - Adhesion molecules: a rheumatologic perspective.

PMID- 9182909
TI  - Autologous hemopoietic stem cell transplantation: a possible cure for rheumatoid
      arthritis?

PMID- 9182910
TI  - In vivo suppression of early experimental osteoarthritis by interleukin-1
      receptor antagonist using gene therapy.
AB  - OBJECTIVE: This study explored the therapeutic effect of interleukin-1 receptor
      antagonist (IL-1Ra), administered by gene transfer, on the progression of
      osteoarthritic (OA) lesions in an experimental dog model. METHODS: Seventeen
      mature mongrel dogs were divided into 3 groups. Group 1 (n = 7) had an anterior
      cruciate ligament (ACL) section of the right knee through a stab wound incision.
      Groups 2 and 3 (n = 5 per group), had an ACL section of the right knee and
      partial synovectomy of the left knee. Each dog's synovium was subjected to
      enzymatic digestion, and the synovial fibroblasts were propagated in monolayer
      culture. Synovial cells from each dog were transduced in vitro using the
      retrovirus MFG with either the Escherichia coli beta-galactosidase (lac Z) gene
      (group 2) or the human IL-1Ra gene (group 3). Two days after surgery, the dogs
      received intraarticular injections as follows: group 1 phosphate buffered saline
      (PBS) (2 ml); group 2 autologous cells (60 x 10(6) cells/2 ml of PBS) transduced
      with the lac Z gene; group 3 autologous cells transduced with the IL-1Ra gene.
      Synovial fluid was aspirated at 2 weeks and 4 weeks. All dogs were euthanized at
      4 weeks postsurgery. The right knees were dissected, and lesions were scored for
      macroscopic and microscopic changes. Synovial explants were dissected and
      representative specimens were used for histology or were cultured for 48 hours.
      The levels of IL-1Ra in synovial fluid and synovial explant conditioned medium
      were measured by specific enzyme-linked immunosorbent assay. RESULTS: The level
      of IL-1Ra in synovial fluid of group 3 was 202.8 +/- 131.5 ng/ml (mean +/- SEM)
      at 2 weeks and 2.8 +/- 2.2 ng/ml at 4 weeks after surgery. Membrane explants
      isolated from dogs that received synovial cells transduced with the IL-1Ra gene
      (group 3) actively produced IL-1Ra (4.0 +/- 2.0 ng/gm of tissue wet weight). The
      severity of OA cartilage lesions was similar in groups 1 and 2. In contrast,
      group 3 dogs had a marked reduction in macroscopic lesion severity on the tibial
      plateaus (P < 0.01 for grade; P < 0.04 for size) and femoral condyles. Moreover,
      the histologic lesion severity was decreased on both plateaus (P < 0.06) and
      condyles. CONCLUSION: This study showed that a local increase in IL-1Ra
      production in OA knee joints by intraarticular injection of transduced synovial
      cells can reduce the progression of experimentally induced lesions.

PMID- 9182911
TI  - Bone morphogenetic protein 2 stimulates articular cartilage proteoglycan
      synthesis in vivo but does not counteract interleukin-1alpha effects on
      proteoglycan synthesis and content.
AB  - OBJECTIVE: To study the effect of bone morphogenetic protein 2 (BMP-2) on
      articular cartilage proteoglycan (PG) synthesis in vivo and to investigate
      whether BMP-2 is able to counteract the effects of interleukin-1 (IL-1) on
      articular cartilage PG synthesis and content. METHODS: BMP-2 alone or in
      combination with IL-1alpha was injected into murine knee joints. PG synthesis was
      measured by 35S-sulfate incorporation using an ex vivo method or autoradiography.
      Cartilage PG content was analyzed by measuring Safranin O staining intensity on
      histologic sections. RESULTS: BMP-2 appeared to be a potent stimulator of
      articular cartilage PG synthesis in vivo. However, BMP-2 was not able to
      counteract the deleterious effects of IL-1alpha on articular cartilage PG
      synthesis and content. In addition, intraarticular injections of BMP-2 induced
      chondrophytes. CONCLUSION: Although BMP-2 is a very potent stimulator of
      cartilage PG synthesis in vivo, the therapeutic applications of BMP-2 are limited
      due to the inability of BMP-2 to counteract the effects of IL-1 and the induction
      of chondrophytes.

PMID- 9182912
TI  - Enhancement of cartilage matrix protein synthesis in arthritic cartilage.
AB  - OBJECTIVE: To investigate whether the synthesis of cartilage matrix protein (CMP)
      is enhanced in arthritic cartilage. METHODS: The content of CMP in human and pig
      cartilage was determined by immunoblotting, and CMP-producing chondrocytes in
      osteoarthritic (OA) and rheumatoid arthritic (RA) joints were immunostained.
      RESULTS: CMP was undetectable in the condylar cartilage and disc of pigs, whereas
      it was abundant in the rib and tracheal cartilage of the same animals. By
      immunohistochemical analysis, CMP was localized in only a few chondrocytes (5%)
      in normal human joints, whereas numerous chondrocytes (>60%) were immunostained
      in RA joints. The number of CMP-producing cells was also increased in OA
      cartilage (>40%). Immunoblotting analyses confirmed that the CMP content in the
      cartilage from OA and RA patients was much higher than that in normal cartilage.
      CONCLUSION: These findings demonstrate that articular chondrocytes can synthesize
      CMP, although it is suppressed under physiologic conditions. The results also
      suggest that articular chondrocytes express CMP in response to arthritic stimuli.

PMID- 9182913
TI  - Changes in messenger RNA and protein levels of proteoglycans and link protein in
      human osteoarthritic cartilage samples.
AB  - OBJECTIVE: To determine the steady-state messenger RNA (mRNA) levels and
      corresponding protein contents of major matrix components in osteoarthritic (OA)
      cartilage. METHODS: Steady-state levels of gene-specific mRNA (relative to GAPDH)
      were measured by quantitative polymerase chain reaction (PCR), and the relative
      levels of the corresponding proteins were determined by Western blotting.
      RESULTS: All mRNA levels and corresponding protein contents of aggrecan and
      versican (hyaluronan-binding large proteoglycans), decorin, biglycan,
      fibromodulin, and lumican (small proteoglycans), and link protein were higher in
      OA cartilage samples than in age-matched normal samples. The ratio of increase,
      however, was different for each component. The mRNA and protein levels of
      biglycan, decorin, and fibromodulin increased synchronously, whereas message for
      link protein and lumican were several-fold higher than expected by their measured
      protein contents. Versican was also detected in OA cartilage; however, the
      versican protein content was associated with a relatively low mRNA level.
      CONCLUSION: The expression of matrix components was increased in chondrocytes of
      OA cartilage, especially the expression of small proteoglycans, most likely due
      to the repair processes. A discoordinate gene expression accompanied with
      imbalanced accumulation of noncollagenous matrix components may contribute to the
      disorganization of the cartilage and the development of OA processes.

PMID- 9182914
TI  - Major role of collagen IIB in the elevation of total type II procollagen
      messenger RNA in the hypertrophic phase of experimental osteoarthritis.
AB  - OBJECTIVE: To define the relative contributions of procollagen IIA and IIB
      messenger RNA (mRNA) in the 8-fold elevation of total (IIA + IIB) type II
      procollagen mRNA in cartilage from joints with early experimental osteoarthritis
      (OA). METHODS: Unilateral cruciate ligament transection was performed on
      skeletally mature animals. Total RNA was extracted from articular cartilage from
      control joints and from joints with experimental OA. Northern blot hybridization
      with oligoprobes was used to distinguish between types IIA and IIB mRNA. RESULTS:
      Levels of IIA mRNA were similar in control and experimental cartilage. Type IIB
      mRNA accounted for the increase in total type II mRNA expression in OA joints.
      CONCLUSION: Although OA chondrocytes adapt to making immature forms of aggrecan
      proteoglycan, they do not revert to the prechondrocyte stage characterized by IIA
      mRNA expression.

PMID- 9182915
TI  - Interleukin-17 up-regulation of nitric oxide production in human osteoarthritis
      cartilage.
AB  - OBJECTIVE: To examine the effect of human interleukin-17 (IL-17) on nitric oxide
      (NO) production in human osteoarthritis (OA) cartilage under ex vivo conditions.
      METHODS: OA cartilage from patients undergoing knee replacement surgery was used
      in explant assays to assess the effect of IL-17. NO production was measured by
      estimating the stable NO metabolite, nitrite, in conditioned medium. RESULTS: IL
      17 augmented the spontaneous production of nitric oxide. This augmentation was
      sensitive to cycloheximide and pyrrolidine dithiocarbamate, but not to
      dexamethasone or soluble IL-1 receptor. CONCLUSION: IL-17 augments nitric oxide
      production in OA cartilage via nuclear factor kappaB activation, but
      independently of IL-1beta signaling.

PMID- 9182917
TI  - The influence of silicone implantation on type II collagen-induced arthritis in
      mice.
AB  - OBJECTIVE: To determine whether silicone implantation exacerbates autoimmune
      disease in a murine experimental model of arthritis. METHODS: DBA/1 mice were
      implanted with silicone in the form of an elastomer, gel, or oil, and immunized
      with type II collagen. The influence of silicone implantation on collagen-induced
      arthritis and the immune response to type II collagen were determined by
      comparison against control mice receiving sham implantation. Adjuvant effects of
      silicone implantation were examined by measuring cytokine levels in implanted
      animals and assessing autoantibodies against proteins extracted from recovered
      silicone implants. RESULTS: No adverse influence of silicone implantation on the
      clinical aspects of collagen-induced arthritis was observed. Further,
      polydimethylsiloxane silicone oil failed to serve as an adjuvant in the immune or
      arthritogenic response to type II collagen in mice. Cytokine analysis indicated
      that tumor necrosis factor alpha levels were lower and interleukin-2 levels were
      higher in silicone-implanted mice. The development of arthritis increased protein
      binding to implanted elastomers and gel, and autoantibodies against silicone
      bound proteins were present in sera from arthritic mice and absent in sera from
      nonarthritic mice. CONCLUSION: The data suggest that silicone implantation may
      result in autoantibodies against silicone-bound proteins, and the presence of
      arthritis may either provoke or increase the level of such autoantibodies.
      However, silicone implantation did not increase the incidence or severity of
      disease compared with sham-operated controls. Thus, it appears that
      autoantibodies against silicone-bound proteins may not have pathologic
      significance in this experimental model of arthritis.

PMID- 9182916
TI  - Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas
      ligand.
AB  - OBJECTIVE: To characterize Fas antigen expression on the cell surface, and to
      determine the effect of this expression in rheumatic diseases using a newly
      established gld-congenic MRL strain of mice (MRL/gld), which is defective in its
      functional Fas ligand (Fas-L). METHODS: Flow cytometric analyses of lymphoid
      cells and macrophages were performed using anti-Fas and other cell surface
      markers. Histopathologic manifestations were examined using immunochemistry and
      light and electron microscopy. Serum levels of IgG and anti-DNA antibodies were
      measured by single radial immunodiffusion and enzyme-linked immunosorbent assay,
      respectively. RESULTS: MRL/gld mice developed systemic lymphadenopathy with an
      accumulation of Thy1.2+, B220+ and CD4-, CD8- T cells, which both express the Fas
      antigen. Splenic B cells positive for surface IgM and/or surface IgD, and
      resident peritoneal macrophages exhibited up-regulated expression of the Fas
      antigen, at much higher levels than those observed in MRL/MpJ-+/+ (MRL/+) mice.
      Forms of rheumatic disease were observed in these mice, although not in C3H/HeJ
      gld/gld mice. These forms included diffuse glomerulonephritis, granulomatous
      arteritis, and arthritis, and were associated with the infiltration of
      mononuclear cells expressing the Fas antigen. Serum levels of IgG and anti-DNA
      antibodies were significantly increased in MRL/gld mice compared with MRL/+ mice.
      CONCLUSION: Rheumatic disease was generated by the gld gene in mice with an MRL
      background, as it is by the lpr gene, which is a Fas deletion mutant, associated
      with autoimmune traits. Rheumatic disease in this MRL strain was initiated by an
      incapacity for Fas/Fas-L-induced apoptosis, resulting in the development of
      autoimmunity and allowing for a persistent immune response in the affected
      lesions.

PMID- 9182918
TI  - Paclitaxel selectively induces mitotic arrest and apoptosis in proliferating
      bovine synoviocytes.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic progressive
      destruction of joints involving several disease processes, such as villous
      hypertrophy, proliferation of synovial lining cells, and infiltration of
      inflammatory cells. Synovial cell activation and proliferation is thought to be a
      key step in the destruction of cartilaginous and bony tissues in RA joints. In
      view of the invasive properties of synoviocytes in RA, we conducted in vitro
      studies to determine the mechanism of action of paclitaxel (Taxol) on
      synoviocytes, which may account for the inhibition of joint destruction found
      when this agent is administered. METHODS: Cultured synovial cells were treated
      with various concentrations of paclitaxel and were evaluated by cell viability,
      fluorescence microscopy, flow cytometry of DAPI-stained cells, and electron
      microscopy. RESULTS: The data indicated that paclitaxel inhibited synoviocyte
      proliferation by a G2/M phase block and was toxic to synoviocytes by inducing
      apoptosis. Confluent cells such as chondroyctes and synoviocytes were not
      affected by paclitaxel. Synchronization of synovioyctes at the G1/S boundary
      effectively abolished paclitaxel-induced apoptosis. CONCLUSION: The data indicate
      that induction of apoptosis in synoviocytes might be dependent on transit through
      the cell cycle, specifically through G2 and mitosis. Further, paclitaxel was
      selectively toxic to proliferating synoviocytes but spared nonproliferating
      synoviocytes and chondrocytes. These results demonstrate that paclitaxel can
      inhibit synovial cell proliferation and pannus formation in RA joints in vivo. We
      suggest that paclitaxel be considered as a prototypical compound for a new class
      of potential chondroprotective agents.

PMID- 9182919
TI  - The transcriptional activator Sp1, a novel autoantigen.
AB  - OBJECTIVE: To identify one nuclear autoantigenic protein within a complex of DNA
      binding proteins that bind to GC-rich sequences in Epstein-Barr virus and
      cellular DNA, and to describe the clinical characteristics of patients whose sera
      contained autoantibodies to this novel autoantigen. METHODS: Antibodies to
      autoantigen Sp1 were initially measured by an electrophoretic mobility shift
      assay to detect DNA binding proteins. Nuclear extracts and purified Sp1 protein
      were used in these assays. Recognition of the autoantigen by autoimmune sera was
      confirmed by immunoprecipitation and immunoblotting. RESULTS: The autoantigen was
      identified as Sp1. Anti-Sp1 was detected in sera from 8 (3%) of 230 patients.
      These sera contained antinuclear antibodies, but lacked antibodies to double
      stranded DNA or to several extractable nuclear antigens. The patients whose sera
      contained antibodies to Sp1 were white women with fatigue, arthritis, Raynaud's
      phenomenon, malar rash, and photosensitivity. CONCLUSION: Sp1 is the first
      described example of an RNA polymerase II transcription activator as an
      autoantigen. The presence of Sp1 autoantibodies is associated with
      undifferentiated connective tissue disease.

PMID- 9182920
TI  - The synovial expression and serum levels of interleukin-6, interleukin-11,
      leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the expression of interleukin-6 (IL-6), IL-11, leukemia
      inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources
      in the joints of rheumatoid arthritis (RA) patients, as well as the correlation
      of circulating levels of these IL-6-type cytokines and C-reactive protein (CRP).
      METHODS: Messenger RNA (mRNA) and protein levels for IL-6, IL-11, LIF, and OSM
      were determined by using reverse transcription-polymerase chain reaction and
      enzyme-linked immunosorbent assay, respectively. RESULTS: Cells isolated from the
      synovium of RA patients expressed mRNA for IL-6, IL-11, LIF, and OSM at higher
      levels than did synovial cells from osteoarthritis (OA) patients, and
      spontaneously released greater quantities of these proteins in culture.
      Fibroblast cell lines derived from RA synovium were able to produce IL-6, IL-11,
      and LIF, but not OSM, when stimulated with IL-1 and tumor necrosis factor alpha.
      OSM was found to be produced spontaneously by synovial tissue macrophages. IL-6,
      IL-11, LIF, and OSM were present in synovial fluid from the RA patients; levels
      of IL-6, LIF, and OSM were present in significantly greater quantities in RA
      patients than in OA patients. However, only IL-6 was significantly elevated in
      the serum of RA patients and correlated with the serum CRP level, while other IL
      6-type cytokines were not detected. CONCLUSION: IL-6, IL-11, LIF, and OSM are all
      produced in large amounts at the site of disease activity, but IL-6 derived from
      synovial fibroblasts may be the major hormone-like mediator that induces the
      hepatic synthesis of acute-phase proteins in RA.

PMID- 9182921
TI  - Expansion of unusual CD4+ T cells in severe rheumatoid arthritis.
AB  - OBJECTIVE: The repertoire of T cells in patients with rheumatoid arthritis (RA)
      is characterized by clonal expansion of selected CD4+ T cells, which are
      autoreactive and lack the expression of the functionally important CD28 molecule.
      The goal of this study was to determine the contribution of these unusual
      lymphocytes to the disease process. METHODS: RA patients (n = 108) and normal
      controls (n = 53) were examined for the expression of CD4+ CD28- T cells by 2
      color fluorescence-activated cell sorter analysis. Clinical data were ascertained
      by retrospective chart review. RESULTS: The frequencies of CD4+ CD28- T cells
      displayed a bimodal distribution, defining carriers and noncarriers in normal
      subjects and RA patients. In longitudinal studies, the noncarrier and carrier
      phenotypes were stable over time. Carriers of CD4+ CD28- T cells accumulated in
      the RA population (64% versus 45%; P = 0.02). The expansion of CD4+ CD28- T cells
      correlated with extraarticular involvement, but not with disease duration,
      antirheumatic treatment, or severity of joint destruction. The patient subsets
      with nodular disease (P = 0.02) and rheumatoid organ disease (P = 0.04) had the
      highest proportion of CD4+ CD28- T cell carriers. The size of the CD4+ CD28-
      compartment correlated with extraarticular progression of RA (P = 0.001 in
      nodular RA, P = 0.003 in rheumatoid organ disease). CONCLUSION: The bimodality of
      distribution of CD4+ CD28- T cell frequencies is compatible with genetic control
      of the generation of these unusual T cells. In RA patients, CD4+ CD28- T cells
      are not an epiphenomenon of the disease process, but predispose patients to
      developing inflammatory lesions in extraarticular tissues.

PMID- 9182922
TI  - Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid
      arthritis.
AB  - OBJECTIVE: To identify a cartilage-derived autoantigen that is relevant to the
      rheumatoid arthritis (RA) disease process. METHODS: A DR4 (DRB1*0401) peptide
      binding motif was used for the selection of potential self reactive peptides
      within human cartilage glycoprotein-39 (HC gp-39), a protein that is
      differentially expressed at the site of chronic inflammation. Synthetic peptides
      accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401)
      molecules. High-affinity binders were then tested for their capacity to stimulate
      peripheral blood mononuclear cell responses in RA patients or healthy donors. To
      assess the arthritogenic nature of native HC gp-39, the protein was injected into
      BALB/c mice. RESULTS: HC gp-39-derived motif-based peptides were selectively
      recognized by peripheral blood T cells from RA patients. Injection of the intact
      protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be
      associated with the development of a chronic, relapsing arthritis. Moreover,
      inhalation of the protein led to tolerization of antigen-specific T cells and to
      suppression of HC gp-39-induced arthritis. CONCLUSION: These data indicate that
      HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a
      candidate for antigen-specific immunotherapy.

PMID- 9182923
TI  - Soluble Fas (APO-1, CD95) and soluble Fas ligand in rheumatic diseases.
AB  - OBJECTIVE: To assess levels of soluble Fas (sFas) and soluble Fas ligand (sFas-L)
      in sera from patients with various rheumatic diseases: systemic lupus
      erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc),
      polymyositis/dermatomyositis (PM/DM), mixed connective tissue disease (MCTD), and
      Sjogren's syndrome (SS). METHODS: Levels of sFas and sFas-L were determined by a
      sandwich enzyme-linked immunosorbent assay. RESULTS: In SLE, PM/DM, MCTD, and SS,
      sFas levels were significantly higher compared with normal controls. Levels of
      sFas in the SLE patients were significantly higher than in patients with other
      rheumatic diseases. Levels of sFas-L were significantly increased in SS patients.
      SLE and RA patients with high levels sFas-L tended to have high levels of sFas,
      while sFas and sFasL levels did not correlate in patients with other diseases. In
      some of the SLE patients, sFas and sFas-L levels decreased following steroid
      therapy. CONCLUSION: Serum sFas and sFas-L levels were significantly higher in
      some rheumatic disease patients. Since these changes are complex in these
      rheumatic diseases, it may be difficult to directly relate sFas and sFasL to
      their pathogenesis.

PMID- 9182924
TI  - Impaired nonrestricted cytolytic activity in systemic lupus erythematosus:
      involvement of a pathway independent of Fas, tumor necrosis factor, and
      extracellular ATP that is associated with little detectable perforin.
AB  - OBJECTIVE: To determine the cytolytic effector pathway involved in impaired
      generation of nonrestricted cytolytic activity in systemic lupus erythematosus
      (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) from normal subjects
      and SLE patients were stimulated in vitro with anti-CD3 monoclonal antibody (MAb)
      and interleukin-2 to promote the generation of nonrestricted cytolytic activity.
      On day 13 of culture, the PBMC were assayed for cytolytic activity against Fas
      Daudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium
      chelation, antagonist anti-Fas MAb, tumor necrosis factor (TNF) alpha and beta,
      and ATP were measured. Intracellular perforin expression was determined by
      intracellular staining, and perforin messenger RNA levels were determined by
      quantitative competitive reverse transcription-polymerase chain reaction.
      RESULTS: We demonstrated the existence of a cytolytic pathway that is independent
      of Fas, TNF alpha, TNF beta, and ATP, but is dependent upon extracellular
      calcium. Despite its calcium dependence, this pathway is associated with low-to
      undetectable levels of perforin. CONCLUSION: Impaired generation of nonrestricted
      cytolytic activity in SLE is likely due to decreased activity of this Fas-, TNF
      alpha-, TNF beta-, ATP-independent pathway associated with very low levels of
      perforin.

PMID- 9182925
TI  - Molecular analysis of major histocompatibility complex allelic associations with
      systemic lupus erythematosus in Taiwan.
AB  - OBJECTIVE: To investigate the association of HLA class II alleles/haplotypes,
      type I C2 deficiency gene, and tumor necrosis factor a gene promoter allele
      (TNF2) with systemic lupus erythematosus (SLE) in the Chinese population in
      Taiwan. METHODS: The HLA-DRB1 and DQB1 alleles were studied in 105 SLE patients
      and 115 controls by the polymerase chain reaction (PCR)/sequence-specific
      oligonucleotide probe method, the subtyping of DRB1*15/16 and DRB5 by PCR with
      sequence-specific primers, type I C2 deficiency gene by PCR, and TNF2 by PCR-Nco
      I restriction fragment length polymorphism. RESULTS: The frequencies of the HLA
      class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2
      associated haplotypes DRB1* 1501,DRB5*0101,DQB1*0602 and DRB1*1502,DRB5*
      0102,DQB1*0501 were higher among SLE patients than among controls; however, only
      DQB1*0501 was statistically significantly associated with SLE. No specific
      allele/haplotype was significantly associated with lupus nephritis. No subject
      had type I C2 deficiency. SLE patients had a marginally higher percentage of
      TNF2, which was in linkage disequilibrium with DR3. Since DR3 was not associated
      with SLE in this Taiwanese Chinese population, TNF2 might play a role in the
      immunopathogenesis of SLE. CONCLUSION: Although no HLA-DRB1 allele was found to
      be significantly associated with SLE, the associations with DQB1*0501 and TNF2
      suggest that DQB1 and tumor necrosis factor a may be important genetic factors in
      SLE susceptibility in the Chinese population in Taiwan.

PMID- 9182926
TI  - The palpable tendon friction rub: an important physical examination finding in
      patients with systemic sclerosis.
AB  - OBJECTIVE: To evaluate the clinical and prognostic significance of palpable
      tendon friction rubs in patients with systemic sclerosis (SSc). METHODS: SSc
      patients evaluated prospectively at the University of Pittsburgh were examined
      serially for the presence of tendon friction rubs on physical examination.
      Demographic, clinical, and laboratory features of disease were obtained by
      patient examination, annual patient questionnaire, and medical record review.
      Patients were classified as having limited or diffuse scleroderma according to
      standard definitions. The prognostic significance of the presence of tendon
      friction rubs was determined using this comprehensive database. RESULTS: The SSc
      patients (n = 1,305) were first evaluated during 1972 through 1991 and were
      followed up for a mean of 6.3 years. Tendon friction rubs were detected most
      frequently in patients who had or who developed diffuse cutaneous involvement.
      There were strong correlations between the presence of tendon friction rubs and
      symptoms and signs typical of diffuse scleroderma, including more severe skin
      thickening, more frequent heart and kidney involvement, and decreased survival.
      In multiple regression analyses, the presence of 1 or more tendon friction rubs
      was one of the best predictors of both evolution to diffuse scleroderma and
      reduced survival. CONCLUSION: The palpable tendon friction rub is an easily
      detected, inexpensively obtained physical examination finding which is highly
      associated with diffuse cutaneous scleroderma and decreased survival. This
      observation should lead to the early diagnosis of diffuse scleroderma and should
      identify patients at high risk for serious visceral involvement who are thus
      candidates for potential disease-modifying therapy.

PMID- 9182927
TI  - Epstein-Barr virus strain type and latent membrane protein 1 gene deletions in
      lymphomas in patients with rheumatic diseases.
AB  - OBJECTIVE: Recent studies have shown that immunomodulatory therapy for the
      treatment of rheumatic diseases can be associated with the development of Epstein
      Barr virus (EBV)-associated lymphoproliferative disorders. The present study was
      undertaken to determine the strain type of EBV in lymphoproliferative disorders
      that occur in patients with rheumatic disease and to investigate EBV latent
      membrane protein 1 (LMP-1) gene deletions that occur in these lymphoproliferative
      disorders. METHODS: Ten EBV-associated lymphoid neoplasms in patients with
      rheumatoid arthritis or dermatomyositis were analyzed by polymerase chain
      reaction to determine EBV strain type and to investigate for the presence of a
      previously characterized 30-basepair deletion in the LMP-1 gene. RESULTS: The
      results indicated that lymphoproliferative disorders in these patients can harbor
      EBV strain type A or B, with a predominance of type A infection (80%). It was
      also shown that both wild-type and mutated LMP-1 genes can be found in these
      neoplasms, with the deleted form of the LMP-1 gene occurring in one-third of
      cases in this series. CONCLUSION: LMP-1 deletions associated with certain
      aggressive lymphoid neoplasms are not required for the genesis of
      lymphoproliferative disorders in patients with rheumatic disease. The relative
      frequencies of type A and type B EBV strains in these lymphoproliferative
      disorders show similarities to the frequencies in patients with post-solid organ
      transplantation immunosuppression-associated lymphoproliferative disorders.

PMID- 9182929
TI  - Human immunodeficiency virus infection in systemic lupus erythematosus.
AB  - This report describes a female patient with systemic lupus erythematosus (SLE)
      who was infected with the human immunodeficiency virus (HIV). Using stored serum,
      the precise timing of HIV seroconversion was determined and the early effects of
      HIV infection on SLE examined. This infection resulted in clinical improvement
      and the disappearance of autoantibody production. A literature review of the
      association between HIV and SLE is provided.

PMID- 9182928
TI  - In vivo mechanisms for the inhibition of T lymphocyte activation by long-term
      therapy with tacrolimus (FK-506): experience in patients with Behcet's disease.
AB  - OBJECTIVE: To examine the in vivo mechanisms of suppression of T lymphocyte
      function in patients with Behcet's disease (BD) undergoing long-term treatment
      with tacrolimus (FK-506). METHODS: Intracellular proteins were analyzed by
      immunoprecipitation and Western blotting. Messenger RNA expression was studied by
      a polymerase chain reaction-based technique. RESULTS: Interleukin-2 production
      was suppressed in patients treated with tacrolimus. This suppression was found to
      be due to inhibition of interactions between activated calcineurin (Cn) and
      nuclear factor of activated T cells (NF-AT), inhibition of cleavage of the
      autoinhibitory domain of the CnA subunit, and inhibition of heterodimer formation
      by CnA and CnB subunits, resulting in the absence of NF-AT in nuclei of the T
      cells. We found that T lymphocytes in some BD patients treated with tacrolimus
      had reduced amounts of FK-506 binding protein (FKBP) in their cytoplasm.
      CONCLUSION: Tacrolimus reduces the Cn activity of T cells in vivo by the
      cumulative effects of several distinct mechanisms. It is plausible that reduced
      amounts of FKBP may be associated with diminished clinical efficacy in some BD
      patients receiving prolonged treatment with tacrolimus.

PMID- 9182931
TI  - Idiopathic transient osteoporosis of the hip.

PMID- 9182930
TI  - Small fiber neuropathy and vasculitis.
AB  - Vasculitis-associated neuropathy usually presents as multiple mononeuropathies or
      sensorimotor polyneuropathies that affect large nerve fibers; painful small fiber
      sensory neuropathy has not previously been described in association with
      vasculitis. This report describes 2 patients with small fiber neuropathy in whom
      vasculitis was found to be present. Patients with small fiber neuropathy for
      which no other cause has been identified should be evaluated for the presence of
      vasculitis.

PMID- 9182932
TI  - Fc gammaRIIA polymorphism as a risk factor for invasive pneumococcal infections
      in systemic lupus erythematosus.

PMID- 9182933
TI  - Pediatric rheumatology: status of the subspecialty in United States medical
      schools.

PMID- 9182935
TI  - Childhood-onset scleroderma from a dermatologist's perspective: comment on the
      article by Vancheeswaran et al.

PMID- 9182934
TI  - Effect of classification on the incidence of polyarteritis nodosa and microscopic
      polyangiitis: comment on the article by Watts et al.

PMID- 9182936
TI  - Which physicians are qualified to evaluate disability in fibromyalgia? Comment on
      the article by Bennett.

PMID- 9182937
TI  - Finger exostosis caused by drumming? Comment on the clinical image report by
      Buttgereit and Burmester.

PMID- 9182938
TI  - Relative risk and attributable risk needed to interpret "factors predictive of
      infection in cyclophosphamide-treated lupus patients": comment on the article by
      Pryor et al.

PMID- 9182939
TI  - CD70 (CD27 ligand) expression by synovial fluid CD4+ T lymphocytes in rheumatoid
      arthritis: comment on the article by Kohem et al.

PMID- 9182940
TI  - A comparative study of alpha2- and beta-adrenoceptor distribution in pigeon and
      chick brain.
AB  - The pharmacological properties and anatomical distribution of alpha2-, beta1- and
      beta2-adrenoceptors in pigeon and chick brains were studied by both homogenate
      binding and tissue section autoradiography. [3H]Bromoxidine (alpha2-adrenoceptor
      ), [3H]CGP 12177 (beta-adrenoceptor) and [125I]cyanopindolol (beta-adrenoceptor)
      were used as radioligands. In both species, [3H]bromoxidine binding to avian
      brain tissue showed a pharmacological profile similar to that previously reported
      for alpha2-adrenoceptors in mammals. Regarding the anatomical distribution, the
      areas with the highest densities of alpha2-adrenoceptors in the pigeon brain
      included the hyperstriatum, nuclei septalis, tectum opticum and some brainstem
      nuclei. Most beta-adrenoceptors found in tissue membranes and sections from chick
      and pigeon brain were of the beta2 subtype, in contrast to what has been reported
      in the mammalian brain, where the beta1 subtype is predominant. A striking
      difference was found between the two species regarding the densities of these
      receptors: while pigeon brain was extremely rich in [125I]cyanopindolol binding
      throughout the brain (mainly cerebellum) in the pigeon, the levels of labelling
      in the chick brain were much lower; the exception was the cerebellum, which
      displayed a higher density than other parts of the brain in both species.
      Overall, our results support the proposed anatomical equivalences between a
      number of structures in the avian and mammalian encephalon.

PMID- 9182941
TI  - Neonatal gamma-ray irradiation impairs learning and memory of an olfactory
      associative task in adult rats.
AB  - Adult neonatally gamma-irradiated rats were compared with control animals in a
      non-spatial olfactory associative task using two different procedures.
      Irradiation induced a clear reduction in the total mean area of the olfactory
      bulbs and hippocampus but not of the orbital prefrontal cortex, diagonal band and
      cell layers of the entorhinal and piriform cortex. The gamma-irradiation affected
      the granule cells of the olfactory bulbs and differentially altered the cell
      layers of the subfields of the ammonic fields and the dorsal and ventral blades
      of the dentate gyrus. In the CA1 ammonic field, dorsal and ventral blades of the
      dentate gyrus, the cellular loss was significant in comparison with control adult
      rats. The behavioural data indicated that irradiated rats were deeply disturbed
      in learning the odour-reward association, and substantially impaired in a
      reversal experiment, but not in the discrimination of the odours per se. The
      cellular loss in the olfactory bulbs, in the CA1 and in the ventral blade of the
      gyrus dentatus was positively correlated with the deficit in behavioural
      performance. The data support the findings that the hippocampal system
      participates in the odour-reward associations and facilitates the long-term
      storage of associations after learning is achieved in this olfactory associative
      task.

PMID- 9182942
TI  - Endothelins promote the activation of astrocytes in rat neostriatum through ET(B)
      receptors.
AB  - The effects of endothelin (ET)-3 and an ET(B) receptor agonist on astrocytic
      activation in rat caudate putamen were examined by an immunohistochemical
      staining of glial fibrillary acidic protein (GFAP), a marker of reactive
      astrocytes. A single injection of 40 pmol ET-3 into rat caudate putamen increased
      the number of GFAP positive cells compared to that in the contralateral saline
      injected side. Ala(1,3,11,15)-ET-1 (40 pmol), an ET(B) receptor agonist, also
      increased the number of striatal GFAP positive cells. The increases in GFAP
      positive cells were maximum (about 150% of the control side) in 1-2 weeks after
      injections of the ETs, and then reduced in 4 weeks. A continuous infusion of
      BQ788, an ET(B) receptor antagonist (23 nmol/day), into the lateral ventricle of
      the cerebrum antagonized the effect of Ala(1,3,11,15)-ET-1, while BQ788 also
      reduced the number of GFAP positive cells in saline-injected caudate putamen.
      Intrastriatal injection of 40 pmol Ala(1,3,11,15)-ET-1 did not affect the number
      of cells stained by B4 isolectin from Griffonia simplicifolia, which labels
      activated microglia/macrophages. Intraperitoneal administration of 5 mg/kg per
      day chloroquine and 0.2 mg/kg per day colchicine did not affect the action of
      Ala(1,3,11,15)-ET-1. These results suggest that activation of ET(B) receptors is
      involved in the induction of reactive astrocytes.

PMID- 9182943
TI  - Stimulation of the ventral subiculum of the hippocampus evokes glutamate receptor
      mediated changes in dopamine efflux in the rat nucleus accumbens.
AB  - The effects of electrical stimulation of the ventral subiculum/CA1 region of the
      hippocampus on changes in dopamine oxidation current (corresponding to dopamine
      efflux) in the nucleus accumbens were examined using in vivo chronoamperometry
      with stearate-graphite paste electrodes in urethane-anaesthetized rats. Burst
      patterned monophasic pulses (10-100 Hz/burst delivered at 0.8-4 Hz) evoked a
      three-component change in dopamine efflux in the nucleus accumbens with an
      initial transient increase in the dopamine signal above baseline, followed by an
      immediate decrease below baseline, and thereafter by a prolonged increase in the
      dopamine signal above baseline. 6-Hydroxydopamine lesions of the mesoaccumbens
      dopamine pathway or transection of the fimbria-fornix blocked all of the evoked
      changes in the dopamine signal. Both the first and third components of enhanced
      dopamine efflux were blocked by microinfusion into the nucleus accumbens of the
      ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic
      acid, 6,7-dinitroquinoxaline-2,3-dione and kynurenate. Burst stimulation-evoked
      decreases in the dopamine signal were abolished following microinfusions into the
      nucleus accumbens of the metabotropic glutamate receptor antagonist (+)-alpha
      methyl-4-carboxyphenylglycine. These results suggest that ventral subiculum/CA1
      glutamatergic inputs to the nucleus accumbens may presynaptically modulate
      dopamine efflux by synaptic activation of both ionotropic and metabotropic
      glutamate receptors in the nucleus accumbens. These glutamate-dopamine
      interactions may constitute part of the mechanisms by which hippocampal signals
      are integrated through selective modulation of dopamine release in the nucleus
      accumbens in both physiological and pathological conditions.

PMID- 9182944
TI  - Protection against oxidative stress-induced neuronal cell death--a novel role for
      RU486.
AB  - Free radicals and oxidative stress-induced neuronal cell death have been
      implicated in a variety of neurological disorders. Therefore, neuroprotection is
      of primary interest in basic and preclinical neuroscience. Here it is shown that
      RU486 (mifepristone), a potent antagonist of progesterone and glucocorticoid
      receptors, protects rat primary hippocampal neurons, clonal mouse hippocampal
      cells and organotypic hippocampal slice cultures against oxidative stress-induced
      neuronal cell death. 10(-5) M RU486 prevents intracellular peroxide accumulation
      and cell death induced by amyloid beta protein, hydrogen peroxide and glutamate,
      neurotoxins that have been implicated in certain neurodegenerative disorders,
      including Alzheimer's disease. RU486 has a significant protective effect that is
      independent of the presence and activation of glucocorticoid or progesterone
      receptors. The neuroprotective activity of this well-studied drug may have an
      impact on therapeutic interventions for neurodegenerative conditions which
      involve peroxidation processes, such as stroke and Alzheimer's disease.

PMID- 9182945
TI  - Excitatory convergence of Y and non-Y information channels on single neurons in
      the PMLS area, a motion area of the cat visual cortex.
AB  - We analysed the receptive field properties of neurons in the posteromedial
      lateral suprasylvian (PMLS) visual cortical area of anaesthetized cats in which
      there was selective conduction block of the largest (Y-type) fibres in one optic
      nerve. As in normal cats, in cats with selective block of one optic nerve the
      great majority of PMLS cells could be activated by photic stimulation through
      either eye. However, the responses evoked by stimulation via the eye with the
      selectively pressure-blocked optic nerve ('Y-blocked eye') were significantly
      weaker than those of the same cells evoked by the stimulation via the normal eye.
      Accordingly, eye dominance histograms were shifted markedly in favour of the
      normal eye. Furthermore, there was a significant shift towards lower preferred
      velocities when PMLS cells were photically stimulated via the Y-blocked eye.
      Finally, when stimulated via the Y-blocked eye, PMLS cells responded poorly or
      not at all to high stimulus velocities (> or = 100 degrees/s). On the other hand,
      a number of receptive field properties, such as the spatial organization of
      receptive fields, the size of the discharge fields, orientation tuning and
      direction selectivity indices, were not significantly affected by the removal of
      the Y input. We conclude that virtually all neurons in the PMLS area of the cat
      receive excitatory input from both Y and non-Y information channels, although the
      Y channel provides the dominant input and makes the principal contribution to the
      detection of high-velocity motion.

PMID- 9182947
TI  - Evidence for the involvement of the mammillary bodies and cingulum bundle in
      allocentric spatial processing by rats.
AB  - Comparisons were made between the behavioural effects of lesions in three inter
      related limbic structures: the mammillary bodies, the fornix and the cingulum
      bundle/cingulate cortex. Cytotoxic lesions of the mammillary nuclei produced a
      marked deficit on reinforced T-maze alternation, but performance gradually
      improved with practice. Subsequent tests in a cross-maze and a radial-arm maze
      showed that the animals with mammillary body lesions failed to use allocentric
      cues, but were able to perform normally in an egocentric discrimination. Three
      groups of rats with different patterns of either crossed or unilateral radio
      frequency lesions of the cingulate region were given the same tasks. The profile
      of results indicated that disruption of those fibres in the cingulum bundle
      connecting the anterior thalamic nuclei with the hippocampal/retrohippocampal
      region was responsible for the observed impairments to T-maze alternation and
      radial-arm maze performance. There was also evidence that disconnection of
      frontal connections in the cingulum bundle might affect perseverative behaviour,
      but not allocentric processing. The results add support to the notion of a
      functional circuit that involves projections from the hippocampus to the
      mammillary bodies and anterior thalamic nuclei, and from there back to
      hippocampal/retrohippocampal regions via the cingulum bundle. This circuit
      appears to be vital for normal allocentric processing.

PMID- 9182946
TI  - Up-regulation of cyclooxygenase-2 expression in cultured microglia by
      prostaglandin E2, cyclic AMP and non-steroidal anti-inflammatory drugs.
AB  - Cyclooxygenase-2, the inducible isoform of cyclooxygenase, is highly expressed in
      microglial cells activated by bacterial lipopolysaccharide and is a major
      regulatory factor in the synthesis of prostanoids, such as prostaglandins,
      prostacyclin and thromboxanes. Since prostanoids are potent modulators of
      inflammation, immune responses and neurotoxicity, the regulation of their
      synthesis may be crucial for balancing microglial neuroprotective and neurotoxic
      activities. The present study shows that expression of cyclooxygenase-2 and
      prostanoid production in cultured rat microglia activated by lipopolysaccharide
      is up-regulated by cyclic AMP (cAMP), as indicated by experiments performed in
      the presence of adenylyl cyclase activators, cAMP analogues and protein kinase A
      specific inhibitors. Exogenous prostaglandin E2 (PGE2), which elevates the cAMP
      level in microglial cells, also increased the lipopolysaccharide-induced
      expression of cyclooxygenase-2 and production of thromboxane in a dose- and time
      dependent manner. The observations that the lipopolysaccharide-induced prostanoid
      production was specifically increased by 11-deoxy-16,16-dm PGE2, a selective
      agonist at the PGE2 receptor EP2 coupled to the activation of adenylyl cyclase,
      and that the enhancing effect of PGE2 was partially prevented by specific
      inhibitors of adenylyl cyclase and protein kinase A, suggest that the up
      regulation of cyclooxygenase-2 expression by PGE2 is mediated by cAMP, through a
      putative microglial EP2 receptor. Unexpectedly, non-steroidal anti-inflammatory
      drugs such as indomethacin and 6-methoxy naphthalene acetic acidic, which inhibit
      cyclooxygenase enzymatic activity and abrogate prostanoid synthesis, caused a
      moderate but consistent up-regulation of cyclooxygenase-2 expression. In
      conclusion, while the strong up-regulation of cyclooxygenase-2 expression by
      exogenous PGE2 appears to be mediated by EP2 receptors and cAMP, the limited down
      regulation caused by anti-inflammatory drug treatments may be either due to
      arachidonic acid metabolites other than PGE2, or to PGE2 itself, acting through a
      distinct cAMP-independent signalling pathway.

PMID- 9182948
TI  - Selectivity of macaque MT/V5 neurons for surface orientation in depth specified
      by motion.
AB  - Area MTN5 in the macaque brain is one of the major cortical regions involved in
      the analysis of retinal image motion. The majority of the neurons in this
      cortical area have non-uniform antagonistic surrounds as components of their
      receptive field complexes. Theoretical studies indicate that such asymmetrical
      surrounds should enable neurons to extract orientation in depth from motion. Here
      we show that nearly half of the MTN5 neurons encode the tilt component of the
      orientation in depth of a plane specified by motion. Furthermore, we show that
      such selectivity for depth from motion depends on the presence of an asymmetrical
      surround and on the speed tuning of those asymmetrical surround influences.

PMID- 9182950
TI  - Neurite outgrowth inhibitor of gliotic brain tissue. Mode of action and cellular
      localization, studied with specific monoclonal antibodies.
AB  - Membranes from injured adult rat brain express a heparan/chondroitin sulphate
      proteoglycan that inhibits neurite outgrowth in vitro. We have developed
      monoclonal antibodies (Mabs) against this proteoglycan, two of which were
      characterized and used for the study of the inhibitor mode of action and
      localization in normal and injured adult brain. The antibodies recognized a
      molecule of apparent molecular weight 200 kDa in Western blots of injured brain
      membranes. One of the Mabs blocked both the inhibition of neurite outgrowth and
      the growth cone collapse activity, associated with the proteoglycan. In adult
      brain, inhibitor immunoreactivity was found predominantly in neurons but, after a
      lesion, it was associated mainly with reactive glial cells. The localization of
      neurite outgrowth inhibitors in reactive glia supports the idea that gliotic
      tissue is largely responsible for the failure of axonal regeneration in mammalian
      CNS.

PMID- 9182949
TI  - Differential expression of syntrophins and analysis of alternatively spliced
      dystrophin transcripts in the mouse brain.
AB  - Expression of syntrophin genes, encoding members of the dystrophin-associated
      protein complex, was studied in the mouse brain. In the hippocampal formation
      there is distinctive co-localization of specific syntrophins with certain
      dystrophin isoforms in neurons, e.g. alpha1-syntrophin with the C-dystrophin in
      CA regions and beta2-syntrophin with the G-dystrophin in the dentate gyrus.
      Expression of the alpha1-syntrophin is predominant in CA regions and the
      olfactory bulb and it is also present in the cerebral cortex and the dentate
      gyrus. The beta2-syntrophin mRNA is most abundant in the dentate gyrus and is
      also evident in the pituitary, the cerebral cortex and in Ammon's horn and in
      traces in the caudate putamen. The choroid plexus was labelled by both alpha1-
      and beta2-syntrophin-specific probes. The expression of syntrophins in the brain
      correlates with expression of dystrophins and dystroglycan. There are brain areas
      such as the cerebral cortex where several different syntrophins and dystrophins
      are expressed together. Syntrophin expression co-localizes with utrophin in the
      choroid plexus and caudate putamen. Finally, no syntrophin was detected in the
      cerebellar Purkinje cells where the specific dystrophin isoform (P-type) is
      present. This specific distribution of syntrophins in the brain is particularly
      interesting, as muscle syntrophin interacts with neuronal nitric oxide synthase.
      This may suggest that the dystrophin-associated protein complex may be involved
      in synaptic organisation and signal transduction machinery in both muscle and
      neurons. The dystrophin isoform, with exons 71-74 spliced out and hence lacking
      syntrophin binding sites, had been believed to be predominant in the brain, but
      our analyses using in situ hybridization, S1 nuclease protection and the semi
      quantitative polymerase chain reaction revealed that this alternatively spliced
      mRNA is a minor, low abundance form in the brain.

PMID- 9182951
TI  - Synchronization of neuronal activity promotes survival of individual rat
      neocortical neurons in early development.
AB  - Neural activity is thought to play a significant role during the development of
      the cerebral cortex. In this study, we examined the effects of global activity
      block or enhancement and the effects of patterned firing on the ability of
      cultured rat neocortical neurons to survive during the second week in vitro,
      beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding
      tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly
      reduced the survival of cortical cells. Increasing neuronal activity by raising
      the external potassium concentration significantly improved the survival of
      cortical neurons. We postulated that in a developing neuronal network the
      survival of nerve cells is regulated by synaptically mediated events that involve
      changes in the intracellular calcium concentration. To examine this question
      further, we monitored the activity of the developing network by optically
      recording the intracellular calcium signals of many neurons simultaneously. These
      recordings show that in low magnesium neocortical neurons express synchronized
      oscillation of their intracellular calcium concentration. The ability of a
      network to synchronize the changes in intracellular calcium of multiple cells
      appeared gradually during the second week in culture, paralleled by both an
      increase in the synaptic density and a decline in the number of surviving
      neurons. By examining the fate of identified cells several days after a recording
      session, we found that those nerve cells that were co-activated with other
      neurons had a significantly higher chance to survive than cells that did not
      participate in synchronized events. These experiments demonstrate that during
      early cortical network development cortical neurons show synchronized firing
      activity and that the survival of neurons is at least partially dependent on this
      pattern of neuronal activity.

PMID- 9182952
TI  - Lymphocyte recruitment following spinal cord injury in mice is altered by prior
      viral exposure.
AB  - The inflammatory response induced by mechanical lesion of the spinal cord is
      known to include the recruitment of neutrophils and macrophages, while the
      involvement of lymphocytes has been largely ignored. We have studied the pattern
      of lymphocyte recruitment following partial transection of the mouse spinal cord.
      Using immunohistochemical techniques, all three types of lymphocytes (CD4
      positive T-cells, CD8-positive T-cells and B-cells) were found in the vicinity of
      the lesion site within hours and persisted for up to 7 days. There was a
      predominance of B-lymphocytes during the first 3 days. A second, late phase of
      cell infiltration, dominated by CD8-positive T-lymphocytes, occurred in mice that
      had been raised in a conventional breeding unit and had acquired antibody titres
      to a common murine virus (mouse hepatitis virus). In contrast, mice kept in
      specific pathogen-free facilities did not show this late-phase response. These
      findings suggest a possible role for lymphocytes in secondary tissue loss, local
      demyelination, scar formation, cytokine-mediated inflammatory responses or
      trophic processes. They also provide evidence that a virus infection can
      significantly enhance the reaction of T-cells to a spinal cord lesion.

PMID- 9182953
TI  - Dopaminergic phenotype induced by oestrogens in a human neuroblastoma cell line.
AB  - Oestrogens are the key factor in the sexual differentiation of the mammalian
      brain and play an important role in the activity of selected areas of the mature
      brain. To pursue the study of oestrogen action on neural cells at the molecular
      level, we developed a human neuroblastoma cell line (SK-ER3) expressing the
      oestrogen receptor (ER). Treatment of these cells with 17beta-oestradiol causes
      growth arrest and morphological and biochemical differentiation. The aim of the
      present study was to investigate whether oestrogen-differentiated SK-ER3
      neuroblastoma cells acquire the ability to synthesize a specific neurotransmitter
      and whether the growth arrest previously reported can be ascribed to the blockage
      of the cells at a specific stage of the cell cycle. The results presented here
      indicate that oestrogens induce accumulation of SK-ER3 cells in the G0 phase of
      the cell cycle, underscoring the acquisition of a mature neural phenotype upon
      hormonal treatment. Most importantly, we show that in the differentiated cells
      the content of tyrosine hydroxylase and Na+-dependent dopamine uptake is
      significantly augmented, proving that the oestrogen-differentiated SK-ER3 cells
      can synthesize and store a specific neurotransmitter. In addition, we prove that
      the dopamine accumulated in differentiated SK-ER3 cells can be released. These
      studies therefore suggest that oestrogen treatment results in the acquisition of
      a fully functional dopaminergic phenotype of SK-ER3 cells. Ample evidence shows a
      link between dopaminergic neurons and oestrogen activity in hypothalamic and non
      hypothalamic areas of the mammalian brain. Our study indicates that oestrogens
      might play a primary role in committing undifferentiated neuroblasts towards the
      dopaminergic phenotype.

PMID- 9182954
TI  - Interaction between neurons in different laminae of the dorsal horn of the spinal
      cord. A correlation study in normal and neuropathic rats.
AB  - Simultaneous recordings of 135 pairs of units, located respectively in the
      superficial (I-IIo) and deep (V) laminae of the dorsal horn of the lumbar spinal
      cord of anaesthetized and paralysed animals, were performed both from normal (62
      pairs) and from peripherally injured (chronically constricted sciatic nerve) rats
      (73 pairs). In each pair, one neuron was classified as nociceptive, responding
      only to noxious stimuli, and the other as a wide dynamic range neuron, responding
      to both non-noxious and noxious stimuli. To understand if some interaction was
      present between diverse neurons modulated by noxious inputs, we used cross
      correlation techniques. The responses of simultaneously recorded pairs of units
      to suprathreshold (5 mA, 0.5 ms) electrical stimuli were used. A clearly delayed
      peak in the cross-correlograms of recordings from normal animals was present,
      indicating connectivity of superficial and deep-layer cells. This feature was not
      present in the cross-correlograms obtained from nerve-injured animals. Even if a
      specific pathway cannot be explicitly assigned to support these functional
      results, an overall connection between superficial and deep layers of the spinal
      cord is suggested. These connections are supposed to be either inactive or
      rearranged in the nerve-injured rats, thus suppressing a well timed coordinated
      connectivity. This anomaly could underlie a reduced degree of functional
      coherence in the modulation of nociceptive spinal inputs in cases of chronic
      pain.

PMID- 9182955
TI  - Contribution of area 17 to cell responses in the striate-recipient zone of the
      cat's lateral posterior-pulvinar complex.
AB  - The cat's lateral posterior-pulvinar complex (LP-pulvinar) contains three main
      representations of the visual field. The lateral part of the LP nucleus (LPl or
      striate-recipient zone) is the only region of these extrageniculate nuclei which
      receives afferents from the primary visual cortex. We investigated the
      contribution of area 17 to the response properties (orientation and spatial
      frequency tuning functions) of LPl neurons by cooling or lesioning the visual
      cortex. Responses of 40 LPl cells were studied before, during and after the
      reversible cooling of the striate cortex. When tested for orientation, a total of
      10 units out of 28 was affected (36%). For most of these cells (eight of 10),
      cooling the visual cortex yielded a reduction of the cells' visual responses
      without altering their orientation-selectivity (there was no significant change
      in the orientation tuning width). For only two cells, inactivation led to an
      increase in the response amplitude. Also, blocking the visual cortex never
      modified the direction-selectivity of LPl cells. When tested for spatial
      frequency, 12 neurons out of 33 were affected (36%) by the experimental protocol.
      In most cases, we observed a reduction in the responses at each spatial frequency
      tested, with no change in tuning bandwidth. For only three LPl cells, the effects
      of inactivation of the visual cortex were restricted to specific spatial
      frequencies, altering the profile of the spatial frequency tuning function. In
      five cats, removing area 17 reduced the proportion of visual neurons in LPl and
      the spared visually evoked responses were noticeably depressed. Despite the
      reduction in responsiveness, a few LPl receptive fields within the cortical
      scotoma were still sensitive to the orientation and/or direction of a moving
      stimulus. This last observation suggests that some properties in LPl could be
      generated either by circuits intrinsic to the LPl or by afferents from
      extrastriate cortical areas. Overall, these results indicate that projections
      from the visual cortex to the striate-recipient zone of the LP-pulvinar complex
      are mainly excitatory. Despite the strong impact of the area 17 projections, our
      data suggest that the extrastriate cortex could also play a role in the
      establishment of response properties in the cat's LPl.

PMID- 9182956
TI  - Tachykinin actions on deep dorsal horn neurons in vitro: an electrophysiological
      and morphological study in the immature rat.
AB  - To assess whether functional neurokinin receptors exist in the deep dorsal horn
      of the rat, the actions of the selective neurokinin-1 receptor (NK1R) agonist
      [Sar9,Met(O2)11]substance P ([Sar9,Met(O2)11]SP), the neurokinin-2 receptor
      (NK2R) agonists [beta-Ala8]NKA(4-10) and GR64349 and the neurokinin-3 receptor
      (NK3R) agonist senktide were examined intracellularly in vitro.
      [Sar9,Met(O2)11]SP (1-4 microM) and senktide (1-2 microM) elicited slow
      depolarizations (<10 mV) associated with increased synaptic activity and cell
      firing. [beta-Ala8]NKA(4-10) (10-20 microM) and GR64349 (0.25-10 microM) caused
      small depolarizations (<2.0 mV) and no firing. Neurons were categorized as either
      'tonic' or 'phasic' depending on their firing response to direct current step
      depolarizations. Tonic neurons, which, unlike phasic neurons, display no spike
      firing accommodation, generated a significantly larger depolarization to the NK1R
      and NK3R agonists. The putative contribution of these receptors to primary
      afferent-mediated synaptic transmission was assessed by testing the NK1R
      antagonist GR82334 (1 microM), the NK2R antagonist MEN10,376 (1 microM) and the
      NK3R antagonist [Trp7,beta-Ala8]NKA(4-10) (1 microM) against the dorsal root
      evoked excitatory postsynaptic potential (DR-EPSP). GR82334 and [Trp7,beta
      Ala8]NKA(4-10) significantly reduced (P < or = 0.05) the duration but not the
      amplitude of the DR-EPSP. MEN10,376 (1 microM) had no effect on DR-EPSP amplitude
      or duration. Morphological detail was obtained for seven biocytin-filled deep
      dorsal horn neurons tested with [Sar9,Met(O2)11]SP. Five neurons responded to the
      NK1R agonist, and two of these had dorsally directed dendrites into the
      substantia gelatinosa. The other three [Sar9,Met(O2)11]SP-sensitive neurons had
      dendrites within deeper laminae. These data support the existence of functional
      NK1Rs and NK3Rs in the deep dorsal horn which may be involved in mediating
      sensory afferent inputs from nociceptors.

PMID- 9182957
TI  - Selective upregulation of cytokine receptor subchain and their intracellular
      signalling molecules after peripheral nerve injury.
AB  - Numerous studies have suggested that growth factors and cytokines play an
      important role in the survival of injured neurons and in neurite elongation.
      Therefore, intracellular signalling pathways activated by growth factors and
      cytokine receptors play an important role in neuronal survival or for the re
      establishment of connection. Since the JAK (janus kinase)-STAT (signal
      transducers and activators of transcription) signal transduction pathway is known
      to play a major role in cytokine receptor signalling, we first examined
      regulation of JAK gene expression following peripheral nerve injury by in situ
      hybridization histochemistry. The rat hypoglossal nerve was axotomized
      unilaterally and the mRNA levels for JAK1, JAK2. JAK3 and TYK2 were examined in
      the hypoglossal nucleus at postoperative times ranging from 1 to 35 days. Among
      the JAK family members, JAK2 and JAK3 were substantially increased in injured
      hypoglossal motoneurons, whereas no significant increases were observed for JAK1
      and TYK2. These changes were further confirmed by immunohistochemistry using
      antibodies specific to JAK2 and JAK3. In addition, we examined the JAK2 and JAK3
      associated cytokine receptor components, IL-2R gamma and gp130, which are common
      to various cytokine receptors. Among these, gp130 immunostaining was upregulated
      after nerve injury. This was also confirmed by in situ hybridization. These
      results suggest that the injured neuron prepares the molecular machinery involved
      in certain cytokine receptor signalling pathways at an early phase of the
      regenerative process, accelerating for the neuron to respond to cytokines that
      may regulate survival and/or neurite elongation.

PMID- 9182958
TI  - Reelin mRNA expression during mouse brain development.
AB  - Using in situ hybridization, expression of the mRNA for reelin, the gene most
      probably responsible for the reeler trait, was studied during mouse brain
      development, from embryonic day 13 to maturity. The highest level of expression
      was found in Cajal-Retzius neurons, while a high signal was also seen in the
      olfactory bulb, the external granular layer of the cerebellum and, particularly
      at early developmental stages, in hypothalamic differentiation fields, tectum and
      spinal cord. A moderate to low level of expression was found in the septal area,
      striatal fields, habenular nuclei, some thalamic nuclei, particularly the lateral
      geniculate, the retina and some nuclei of the reticular formation in the central
      field of the medulla. Paradoxically, no reelin expression was detected in radial
      glial cells, the cortical plate, Purkinje cells, inferior olivary neurons and
      many other areas that are characteristically abnormal in reeler mutant mice.
      Together with other preliminary studies, the present observations suggest that
      the action of reelin is indirect, possibly mediated by the extracellular matrix.
      Most of the data can be explained by supposing that reelin is a cell-repulsive
      molecule which prevents migrating neurons from invading reelin-rich areas, and
      thus facilitates the deployment of radial glial cell processes and the formation
      of early architectonic patterns.

PMID- 9182959
TI  - Magnetoencephalography may help to improve functional MRI brain mapping.
AB  - The validity of functional magnetic resonance imaging (FMRI) brain maps with
      respect to the sites of neuronal activation is still unknown. One source of
      localization error may be pixels with large signal amplitudes, since such pixels
      may be expected to overlie large vessels, running remote from the centre of
      neuronal activation. In this study, magnetoencephalography was used to determine
      the centre of neuronal activation in a simple finger tapping task. The
      localization accuracy of conventional FMRI depending on FMRI signal enhancement
      was investigated relative to the magnetoencephalography reference. The results
      show a deterioration of FMRI localization with increasing signal amplitude
      related to increased contributions from large vessels. We conclude that FMRI data
      analysis should exclude large signal amplitudes and that magnetoencephalography
      may help to improve FMRI brain mapping results in a multimethod approach.

PMID- 9182960
TI  - Synaptic plasticity in dissociated hippocampal cultures: pre- and postsynaptic
      contributions.
AB  - The distinction between pre- or postsynaptic expression of synaptic plasticity is
      difficult to make, unless the postsynaptic receptors can be investigated in
      isolation. We have studied single synaptic contacts in dissociated cultures of
      rat hippocampus. The reaction of postsynaptic receptor assemblies to the
      induction of synaptic plasticity was measured and compared with changes in the
      rate of spontaneous miniature excitatory postsynaptic currents (mEPSCs), which
      can reflect changes in the transmitter release mechanism. The response of a
      receptor assembly to locally applied exogenous glutamate was measured before and
      after synchronized application of glutamate and a train of postsynaptic
      depolarizations ('pairing'). Pairing induced a variety of changes: (i) the
      majority of the receptor assemblies showed no change in their response to
      glutamate before and after pairing; (ii) the postsynaptic current due to
      exogenous glutamate showed a rapid increase in five out of 26 cases. This was not
      due to changes in the single channel conductance; (iii) the rate of mEPSCs
      increased, if it had previously been below 25 Hz; (iv) the rate of mEPSCs
      decreased, if it had previously been above 25 Hz. Effects 2 and 3 were blocked by
      antagonists of NMDA receptors. These findings provide direct evidence for an
      increase of the number of glutamate receptors at a subset of the investigated
      postsynaptic sites during synaptic potentiation.

PMID- 9182961
TI  - The perceptual grouping criterion of colinearity is reflected by anisotropies of
      connections in the primary visual cortex.
AB  - An important step in the processing of visual patterns is the segmentation of the
      retinal image. Neuronal responses evoked by the contours of individual objects
      need to be identified and associated for further joint processing. These grouping
      operations are based on a number of Gestalt criteria. Here we report that
      connections in the visual cortex of the cat exhibit a highly significant
      anisotropy, preferentially linking neurons activated by contours that have
      similar orientation and are aligned colinearly. These anatomical data suggest a
      close relation between the perceptual grouping criterion of colinearity and the
      topology of tangential intracortical connections. We propose that tangential
      intracortical connections support perceptual grouping by modulating the saliency
      of distributed cortical responses in a context-dependent way. The present data
      are compatible with the hypothesis that the criteria for this grouping operation
      are determined by the architecture of the tangential connections.

PMID- 9182962
TI  - Visual control of hand-reaching movement: activity in parietal area 7m.
AB  - The activity of single neurons was studied in parietal area 7m while monkeys
      performed an instructed-delay reaching task to visual targets under normal light
      conditions and in darkness. The task was aimed at assessing the influence of
      vision of hand position on the neural activity of 7m related either to static
      posture and movement of the hand or to eye position in the orbit. The results
      show the existence of preparatory, movement-related and postural activity for the
      control of reaching, all of which are strongly modulated by vision. The activity
      of many 7m neurons, otherwise insensitive to pure visual stimuli, seems to
      reflect complex interactions between gaze angle and hand position in the visual
      field.

PMID- 9182963
TI  - Dopaminergic neurons in the rat retina express dopamine D2/3 receptors.
AB  - The localization of dopamine D2 and D3 receptors in the rat retina was studied
      using a polyclonal antibody raised against a peptide sequence common to the
      dopamine D2 and D3 receptors (D2/3). The D2/3 receptor antibody labelled a small
      number of somata in the innermost part of the inner nuclear layer and in the
      ganglion cell layer and a small number of photoreceptor outer segments. Processes
      in both plexiform layers were also labelled. Double-labelling experiments with
      the antibody against the D2/3 receptor and an antibody against tyrosine
      hydroxylase to label dopaminergic neurons resulted in the co-localization of the
      two antibodies. This demonstrates directly that dopaminergic neurons in the
      retina express D2/3 receptors. As previous biochemical and physiological studies
      have demonstrated that activation of D2-like receptors inhibits the release of
      dopamine in the retina, the present results suggest that the D2/3 receptors on
      dopaminergic neurons function as autoreceptors.

PMID- 9182964
TI  - Nerve growth factor treatment increases stimulus-evoked release of sensory
      neuropeptides in the rat spinal cord.
AB  - In the adult rat, nerve growth factor (NGF) upregulates the nociceptive peptide
      substance P (SP) and calcitonin gene-related peptide (CGRP) in neuronal cell
      bodies of C fibres but the effects of NGF on release of these neuropeptides from
      the central afferent terminals have not been reported. Thus, this study compared
      rats treated with six doses of NGF over 2 weeks with controls and measured the
      release of the neuropeptides, SP and CGRP from the dorsum of the lumbar spinal
      cord in vitro. NGF (1.0 mg/kg s.c.) greatly increased basal and stimulus-evoked
      SP and CGRP release; at 0.1 mg/kg, NGF did not affect SP release but
      significantly increased CGRP basal outflow and evoked release. In a different set
      of experiments, topical application of NGF (100 ng/ml) to cords from naive rats
      did not increase stimulus-evoked release of SP or CGRP. These findings show
      marked stimulation by NGF treatment in vivo of release of sensory neuropeptides
      during stimulation of dorsal roots, albeit at relatively large doses of the
      neurotrophin.

PMID- 9182965
TI  - Tamoxifen: the herald of a new era of preventive therapeutics.

PMID- 9182966
TI  - Cytotoxic drugs, programmed cell death, and the immune system: defining new roles
      in an old play.

PMID- 9182968
TI  - HIV infection with Hodgkin's disease: the virus makes a difference.

PMID- 9182967
TI  - Human papillomavirus variants: implications for natural history studies and
      vaccine development efforts.

PMID- 9182969
TI  - Friends of Cancer Research testify at Senate: cancer funding should be doubled.

PMID- 9182970
TI  - Panel grapples with the legacy of "race medicine" in research.

PMID- 9182971
TI  - "Funding first" launched by Lasker trust.

PMID- 9182972
TI  - Ministers discuss Middle East priorities.

PMID- 9182973
TI  - Studies show prophylactic surgeries seem to reduce cancer risk.

PMID- 9182974
TI  - Breast cancer: weighing the evidence for a promoting role of dietary fat.
AB  - It has been hypothesized that a high-fat diet promotes the development of
      postmenopausal breast cancer. This contention is supported by data showing high
      international correlations between fat intake and breast cancer rates, modest
      positive associations with a high-fat diet in case-control studies, and animal
      model studies that have consistently demonstrated that dietary fat influences
      mammary cancer development at several stages in the carcinogenic process. A
      number of plausible biologic mechanisms have been suggested that may explain such
      promotional effects. In contrast, dietary fat intake is unrelated to the risk of
      breast cancer in cohort studies. The conflicting findings from cohort studies
      have created uncertainty regarding nutritional recommendations and breast cancer
      prevention. After reviewing key scientific findings that are relevant to this
      issue, the following conclusion is drawn: In the absence of data from dietary
      intervention trials, the weight of available evidence suggests that the type and
      amount of fat in the diet is related to postmenopausal breast cancer and that the
      inability to detect associations within populations (cohort studies) is because
      of measurement error and the relative homogeneity of diets measured. It is
      expected that the results from intervention trials will clarify this issue.

PMID- 9182975
TI  - Coronary heart disease mortality and adjuvant tamoxifen therapy.
AB  - BACKGROUND AND PURPOSE: Data from randomized clinical trials in Scotland and
      Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer
      have suggested that the drug may also reduce the risk of coronary heart disease.
      In view of these findings, we examined mortality from coronary heart disease
      among patients with early stage breast cancer who were enrolled in the National
      Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy.
      METHODS: Deaths occurring among women who were randomly assigned to 5 years of
      either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to
      determine the cause. Three categories of heart disease-related death were
      defined: 1) death from a definite fatal myocardial infarction, 2) death from
      definite fatal coronary heart disease/possible myocardial infarction, and 3)
      death from possible fatal coronary heart disease. Comparisons of the findings by
      treatment group were made on the basis of average annual hazard (i.e., death)
      rates and the corresponding relative hazard of death. RESULTS: The average annual
      death rate from coronary heart disease was lower for patients who received
      tamoxifen than for patients who received placebo, but the difference was not
      statistically significant. There were eight definite heart-related deaths (i.e.,
      definite fatal myocardial infarction or definite fatal coronary heart
      disease/possible myocardial infarction) among the patients who received
      tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were
      12 definite heart-related deaths among the patients who received placebo,
      yielding an average annual rate of 0.94 per 1000. The corresponding relative
      hazard of death from definite fatal heart disease (tamoxifen versus placebo) was
      0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group
      and 10 deaths in the placebo group were classified as possible cases of fatal
      coronary heart disease. When these cases and the definite cases were considered
      together, the average annual death rate for the patients who received tamoxifen
      was 1.48 per 1000, and the rate for the patients who received placebo was 1.73
      per 1000. The corresponding relative hazard of death was 0.85 (95% confidence
      interval = 0.46-1.58). CONCLUSIONS: The findings from the B-14 trial are
      consistent with the findings from the Scottish and the Swedish trials, suggesting
      that tamoxifen treatment reduces coronary heart disease among patients with
      breast cancer. Continued follow-up of the patients in these trials and in ongoing
      prevention trials is needed to accumulate enough data so that reliable
      conclusions can be drawn about the benefits of tamoxifen in preventing heart
      disease.

PMID- 9182976
TI  - Sensitization of cancer cells treated with cytotoxic drugs to fas-mediated
      cytotoxicity.
AB  - BACKGROUND: The transmembrane receptor Fas, together with its protein-binding
      partner (Fas ligand), is a key regulator of programmed cell death (i.e.,
      apoptosis). Fas and Fas ligand also influence the ability of cytotoxic T
      lymphocytes and natural killer cells to eliminate tumor cells. However, by
      inducing apoptosis in activated T cells, the Fas/Fas ligand system may protect
      some tumor cells from clearance by the immune system. Anticancer drugs enhance
      Fas ligand expression on the surface of Fas receptor-expressing leukemia cells,
      thus suggesting that apoptosis caused by these drugs may be mediated via the
      Fas/Fas ligand system. PURPOSE: This study was conducted to further investigate
      the relationship between the modulation of Fas receptor gene and protein
      expression by treatment of cells with cytotoxic drugs and the immune clearance of
      tumor cells. METHODS: Fas expression on human HT29 colon carcinoma cells treated
      with a variety of anticancer drugs (cisplatin, doxorubicin, mitomycin C,
      fluorouracil, and camptothecin) was analyzed by use of quantitative flow
      cytometry. Human HCT8R and HCT116 colon carcinoma cells and human U937 leukemia
      cells were treated with cisplatin only and analyzed in the same way. Fas ligand
      messenger RNA and protein levels were studied by use of a reverse transcription
      polymerase chain reaction assay and by flow cytometry. Fas gene expression and
      messenger RNA levels in cisplatin-treated HT29 cells were characterized by use of
      in vitro nuclear run-on and northern blot hybridization assays. The cytotoxic
      activities of agonistic anti-Fas antibodies, Fas ligand, and allogeneic
      peripheral blood leukocytes, in the absence or presence of Fas-blocking
      monoclonal antibodies, against tumor cells were assessed by methylene blue
      staining and chromium-51 release assays. RESULTS: Clinically relevant
      concentrations of cisplatin, doxorubicin, mitomycin C, fluorouracil, or
      camptothecin enhanced Fas receptor expression on the plasma membrane of HT29
      cells. Cisplatin-mediated increases in Fas expression were confirmed in HCT8R,
      HCT116, and U937 cells. The enhancement of Fas protein expression was associated
      with an increased sensitivity of cisplatin-treated tumor cells to agonistic anti
      Fas antibodies, to soluble Fas ligand, and to allogeneic peripheral blood
      leukocyte-mediated cytotoxicity. Each of these effects was blocked by co
      treatment of the cells with antagonistic anti-Fas antibody. CONCLUSION AND
      IMPLICATIONS: In addition to their direct cytotoxic effects, chemotherapeutic
      drugs sensitize tumor cells to Fas-mediated cytotoxicity and Fas-dependent immune
      clearance. On the basis of these findings, new strategies might be developed to
      improve the efficacy of these drugs.

PMID- 9182977
TI  - Economic implications of hepatic arterial infusion chemotherapy in treatment of
      nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer.
AB  - BACKGROUND: Approximately 20% of patients with colorectal cancer die of
      metastases confined to the liver. A meta-analysis recently performed by our group
      confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'
      deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or
      supportive care (including symptom palliation when necessary), improved tumor
      response. PURPOSE: Because of the high cost of hepatic arterial infusion, we
      undertook a cost-effectiveness analysis that related the cost of such therapy to
      its medical efficacy. METHODS: The patient population was drawn from the seven
      randomized clinical trials included in the meta-analysis and included individual
      data on 654 patients. Of these seven trials, five compared hepatic arterial
      infusion and intravenous chemotherapy and two compared hepatic arterial infusion
      and a control group in which some patients could be left untreated. Patients
      assigned to receive hepatic arterial infusion made up the hepatic arterial
      infusion group; the other patients constituted the control group. The measures of
      efficacy were survival and tumor response. Health-care costs (in 1995 U.S.
      dollars) were computed over the duration of patient follow-up and were derived
      from actual costs in two centers, one at Henri Mondor Hospital (Paris, France)
      and the other at Stanford University Medical Center (Palo Alto, CA). The total
      cost of treatment included the initial procedure, chemotherapy cycles, and main
      complications. RESULTS: The mean gain in life expectancy in the hepatic arterial
      infusion group compared with the control group was 3.2 months (standard error =
      1.0 month). For patients treated by hepatic arterial infusion in Paris, the
      hepatic arterial infusion pump, initial hospitalization, and the entire process
      (including follow-up and complications) cost, on average, $8400, $15172, and
      $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208,
      respectively. For patients in the control groups in Paris and Palo Alto, the
      total treatment costs were, on average, $9926 and $5928. The additional costs of
      hepatic arterial infusion over control treatment were $19636 in Paris and $19280
      in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the
      additional benefit) with respect to survival of the patients in the hepatic
      arterial infusion group compared with the patients in the control group was
      $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS
      AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal
      liver metastases is within the range of accepted treatments for serious medical
      conditions, although it might be considered borderline by policy-makers in some
      countries. Prospective clinical trials should be conducted to more definitively
      answer this question.

PMID- 9182979
TI  - Inhibition of rat prostate carcinogenesis by a 5alpha-reductase inhibitor, FK143.
AB  - BACKGROUND: Androgen levels in the prostate may influence carcinogenesis in this
      organ. Inhibitors of the enzyme 5alpha-reductase block conversion of testosterone
      to the more active androgen dihydrotestosterone. The use of a 5alpha-reductase
      inhibitor, finasteride, in the chemoprevention of prostate cancer is being
      evaluated in a clinical trial. PURPOSE: This study was conducted to determine if
      a 5alpha-reductase inhibitor, FK143, inhibits the development of prostate cancer
      in rats. METHODS: Male ACI/Seg rats, which spontaneously develop prostate cancer,
      were randomly assigned at 80 weeks of age to receive one of three diets (n =
      35/group) containing 0 (i.e., control group), 20, or 200 ppm FK143. At 140 weeks
      of age, the animals were killed, and the prostates were removed and examined for
      histopathologic features in addition to being assayed for androgen
      concentrations. Two-sided statistical tests were used to calculate all P values.
      RESULTS: The incidence of prostate carcinoma in the control group was 62.9% (22
      of 35 rats); in the group fed the 20 ppm FK143-containing diet, it was 45.7% (16
      of 35); and in the group fed the 200 ppm FK143-containing diet, it was 67.6% (23
      of 34) (overall, P = .153). The corresponding incidences of macroscopic lesions
      were 17.1% (six of 35 rats), 0% (none of 35), and 23.5% (eight of 34),
      respectively (overall, P = .004). The incidence of macroscopic lesions in the
      prostates of rats in the 20-ppm diet group was significantly lower than that in
      the control group (P = .029) or that in the 200-ppm diet group (P = .003).
      Intraprostatic dihydrotestosterone content was significantly lower in rats in the
      groups fed diets containing 20 or 200 ppm FK143 (mean values: 4.51 and 4.33 pg/mg
      wet weight of prostate tissue, respectively) than in the control group (6.10
      pg/mg) (overall, P<.001); by contrast, testosterone was higher in the 200-ppm
      diet group (2.09 pg/mg) than in the control group (1.08 pg/mg) or the 20-ppm diet
      group (1.21 pg/mg) (overall, P<.001). CONCLUSIONS: FK143, when fed to rats at 20
      or 200 ppm, significantly reduced the level of dihydrotestosterone in their
      prostate tissue. However, the incidence of macroscopic cancer in the prostate was
      suppressed in rats consuming the 20 ppm FK143-containing diet but not in those
      consuming the 200-ppm diet. The lack of dose dependence for the chemopreventive
      activity of FK143 may be explained by the reciprocal increase of tissue
      testosterone in the 200-ppm diet group. IMPLICATIONS: The 5alpha-reductase
      inhibitor FK143 may, at specific doses, reduce the incidence of spontaneously
      developing prostate cancer; however, whether these findings in rats will apply to
      humans remains to be determined.

PMID- 9182978
TI  - Genomic variation of human papillomavirus type 16 and risk for high grade
      cervical intraepithelial neoplasia.
AB  - BACKGROUND: Epidemiologic studies have demonstrated strong and consistent
      associations between the detection of human papillomavirus (HPV) type 16 DNA and
      the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer.
      However, HPV16 is also the most common type of HPV in the normal population, and
      only a minority of women with HPV16 infection develop cervical cancer. Studies of
      genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant
      forms in all human populations examined to date. It is conceivable that the
      natural variants of HPV16 in a given population may not have the same biologic
      behavior. PURPOSE: This study was designed to determine the association between
      natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most
      important precancerous lesions of the uterine cervix. METHODS: Prospective
      studies were conducted among 1) women attending a university and 2) women
      presenting to a sexually transmitted disease clinic. Subjects were eligible for
      inclusion in this investigation if the initial cytologic findings did not reveal
      CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)
      based method in one or more cervical or vulvovaginal samples. Eligible subjects
      were followed every 4 months with cervical Pap smears and colposcopic
      examinations. Women were referred for biopsy if cytology or colposcopy suggested
      CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were
      determined by means of single-strand conformation polymorphism (SSCP) analysis of
      PCR products from the noncoding region of the viral genome. Representative SSCP
      patterns from HPV16 variants were further characterized by direct DNA sequencing
      of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were
      calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted
      for 79% of the HPV16 detected in university students and 86% of the virus
      detected in patients presenting to the sexually transmitted disease clinic. CIN 2
      3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the
      university and in 10 of 66 HPV16-positive women presenting to the sexually
      transmitted disease clinic. Among university students, those with HPV16
      nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to
      develop CIN 2-3 than those with prototype-like variants. A similar association
      was observed among women presenting to the sexually transmitted disease clinic
      (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of
      developing CIN 2-3 is not the same with all variants of HPV16 and that
      nonprototype-like variants confer a greater risk compared with prototype-like
      variants. The important genomic differences underlying this increased risk of CIN
      2-3 remain to be determined.

PMID- 9182980
TI  - Tumor necrosis factor-alpha and expression of the multidrug resistance-associated
      genes LRP and MRP.
AB  - BACKGROUND AND PURPOSE: Cancer cells that express P-glycoprotein, multidrug
      resistance-associated protein (MRP), or lung resistance protein (LRP) have
      demonstrated resistance to a wide variety of chemotherapeutic drugs. Recently, we
      reported that human colon carcinoma cells that express all three proteins exhibit
      reduced P-glycoprotein gene expression and a loss of multidrug resistance after
      exposure to tumor necrosis factor-alpha, a hormone-like protein produced by cells
      of the immune system. In this study, we examined the effects of tumor necrosis
      factor-alpha on MRP and LRP gene expression in the same colon carcinoma cells.
      METHODS: HCT15 and HCT116 colon carcinoma cells were incubated with tumor
      necrosis factor-alpha at 100 U/mL for 2, 12, 24, 48, or 72 hours; alternatively,
      cells transfected with an expression vector containing a human tumor necrosis
      factor-alpha complementary DNA were studied. The effects of tumor necrosis factor
      alpha on MRP and LRP messenger RNA expression were evaluated by means of reverse
      transcription and the polymerase chain reaction; effects on MRP and LRP protein
      expression were examined by use of specific monoclonal antibodies and flow
      cytometry. The flow cytometry data were analyzed by use of the two-sided,
      nonparametric Mann-Whitney rank sum test. RESULTS: Treatment with exogenous tumor
      necrosis factor-alpha reduced the level of LRP messenger RNA in both cell types
      in an apparently time-dependent fashion; in HCT15 cells, almost no LRP messenger
      RNA was detected after 48 hours of treatment. In contrast, the level of MRP
      messenger RNA was increased in HCT116 cells by such treatment, but the level in
      HCT15 cells was unchanged. Treatment with exogenous tumor necrosis factor-alpha
      induced changes in LRP and MRP protein expression in the two cell types that
      paralleled the changes found for messenger RNA. In transfected cells, the
      endogenous production of tumor necrosis factor-alpha reduced LRP gene expression
      (both messenger RNA and protein) and increased MRP gene expression (both
      messenger RNA and protein), regardless of cell type. CONCLUSION: In human colon
      carcinoma cells, tumor necrosis factor-alpha influences MRP and LRP gene
      expression in opposite ways. The findings for LRP gene expression parallel our
      earlier findings for P-glycoprotein expression in these cells. IMPLICATION: In
      developing strategies for overcoming multidrug resistance in tumor cells, the
      possibility that an agent can suppress one or more mechanisms of drug resistance
      and enhance others should be considered.

PMID- 9182981
TI  - Medical history risk factors for non-Hodgkin's lymphoma in older women.

PMID- 9182982
TI  - Use of an NK1 receptor antagonist to prevent delayed emesis after cisplatin.

PMID- 9182983
TI  - An explanation for the increasing incidence of testis cancer: decreasing age at
      first full-term pregnancy.

PMID- 9182984
TI  - Prospective study of sex hormone levels and risk of prostate cancer.

PMID- 9182985
TI  - Involuntary smoking and lung cancer: a case-control study.

PMID- 9182986
TI  - Copper A of cytochrome c oxidase, a novel, long-embattled, biological electron
      transfer site.
AB  - This review traces the history of understanding of the CuA site in cytochrome c
      oxidase (COX) from the beginnings, when few believed that there was any
      significant Cu in COX, to the verification of three atoms Cu/monomer and to the
      final identification of the site as a dinuclear, Cys-bridged average valence
      Cu1.5+ ... Cu1.5+ structure through spectroscopy, recombinant DNA techniques, and
      crystallography. The critical steps forward in understanding the nature of the
      CuA site are recounted and the present state (as of the end of 1996) of our
      knowledge of the molecular and electronic structure is discussed in some detail.
      The contributions made through the years by the development of methodology and
      concepts for solving the enigma of CuA are emphasized and impediments, often
      rooted in contemporary preconceptions and attitudes rather than solid data, are
      mentioned, which discouraged the exploitation of early valuable clues. Finally,
      analogies in construction principles of polynuclear Cu-S and Fe-S proteins are
      pointed out.

PMID- 9182987
TI  - Identification of a short sequence highly divergent between beta-adrenergic
      receptor kinases 1 and 2 that determines the affinity of binding to betagamma
      subunits of heterotrimeric guanine-nucleotide-binding regulatory proteins.
AB  - A 28-residue peptide (peptide G), derived from the C-terminal (W643-S670) of the
      beta-adrenergic receptor kinase (betaARK), was previously identified as the
      critical domain for binding to the betagamma subunits of the heterotrimeric
      guanine-nucleotide-binding regulatory protein (G betagamma). We observed that the
      18-amino-acid core of this domain is poorly conserved between betaARK1 and
      betaARK2 and so may provide the basis for differences in G betagamma-binding
      properties. Specific antibodies raised against 18-residue peptides derived from
      the divergent sequences (peptides P1 and P2 for betaARK1 and betaARK2,
      respectively) competitively inhibited G betagamma-activation of the related
      betaARK subtype, confirming the involvement of this region in binding to G
      betagamma. Peptides P1 and P2 inhibited G betagamma-stimulated activity of both
      betaARK1 and betaARK2, with P2 being significantly more potent than P1 (IC50 of
      179+/-5 microM for P2 and >500 microM for P1). The 28-residue peptides G showed
      the same relative inhibitory activities (IC50 = 48+/-5 microM for G2 and 146+/-8
      microM for G1). This relative order of potency G2 > G1 approximately P2 > P1 was
      confirmed in a direct G betagamma-binding assay. No binding selectivity for the
      beta1, beta2, beta3 and beta4 G beta subtypes was observed. The EC50 value for G
      betagamma-activation of betaARK1 was about double of that for betaARK2,
      indicating a higher affinity between G betagamma and betaARK2, which is the
      expected result based on the findings with the peptides. These findings show that
      the 18-residue peptides P represent the shortest sequence of betaARK that can
      bind to G betagamma and provide a demonstration of a functional difference
      between the G betagamma binding domains of betaARK1 and betaARK2.

PMID- 9182988
TI  - NADH oxidase activity of human xanthine oxidoreductase--generation of superoxide
      anion.
AB  - Human xanthine oxidase was purified from breast milk. The dehydrogenase form of
      the enzyme, which predominates in most mammalian tissues, catalyses the oxidation
      of NADH by oxygen, generating superoxide anion significantly faster than does the
      oxidase form. The corresponding forms of bovine enzyme behave very similarly. The
      steady-state kinetics of NADH oxidation and superoxide production, including
      inhibition by NAD, by the dehydrogenase forms of both enzymes, are analysed in
      terms of a model involving two-stage recycling of oxidised enzyme. Established
      inhibitors of xanthine oxidoreductases (allopurinol oxypurinol, amflutizole and
      BOF 4272), which block all other reducing substrates, were ineffective in the
      case of NADH. Diphenyleneiodonium, on the other hand, was a powerful inhibitor of
      NADH oxidation. The potential involvement of reactive oxygen species arising from
      NADH oxidation by xanthine oxidoreductase in ischaemia-reperfusion injury and
      other disease states, as well as in normal signal transduction, is discusssed.

PMID- 9182989
TI  - Human ribosomal protein L7 binds RNA with an alpha-helical arginine-rich and
      lysine-rich domain.
AB  - In this study we mapped the RNA-binding domain of human ribosomal protein L7 and
      characterized its conformation-dependent RNA-binding specificity. Binding
      competition assays demonstrated preferential binding of L7 to mRNAs and rRNA, but
      not to tRNA. The ribohomopolymer poly(G) is bound with high affinity whereas
      poly(U), poly(C), or poly(A) show low affinity to L7. Furthermore, L7 binds to
      double-stranded but not to single-stranded DNA. Deletion mapping showed that the
      RNA-binding domain of L7 is represented by an arginine-rich and lysine-rich
      oligopeptide (ELKIKRLRKKFAQKMLRKARRK), which is reminiscent of the arginine-rich
      motif (ARM) found in one family of RNA-binding proteins. The isolated RNA-binding
      domain is capable of high-affinity binding to the Rev-responsive element (RRE) of
      human immunodeficiency virus type 1 in vitro. Circular dichroic studies
      demonstrated a concentration-dependent and ligand-induced alpha-helical
      transition of a synthetic peptide carrying the arginine-lysine-rich RNA-binding
      domain of protein L7. Peptides carrying a mutation that destroys the alpha
      helical conformation do not bind RNA.

PMID- 9182990
TI  - A conditional-lethal translation termination defect in a sup45 mutant of the
      yeast Saccharomyces cerevisiae.
AB  - Genetic studies have indicated that the product of the yeast SUP45 gene encodes a
      component of the translational-termination machinery. In higher eukaryotes, genes
      similar to SUP45 encode eukaryote release factor 1 (eRF1), which has a stop-codon
      dependent peptidyl-release activity. Using a conditional-lethal mutant allele of
      SUP45 (sup45-2) and a combination of in vivo and in vitro approaches, we
      demonstrate that the product of the SUP45 gene (Sup45p or eRF1) is a factor
      required for translation termination in yeast. A homologous in vitro assay based
      on suppressor-tRNA-mediated readthrough of stop codons is used to show that a
      translating lysate from a sup45-2 mutant strain exhibits a termination defect
      when heated for short periods to greater than the non-permissive temperature (37
      degrees C). This defect can be complemented with a purified preparation of Sup45p
      (eRF1) expressed in Eschericha coli. The termination defect in this strain
      appears to be due to an inability of the Sup45p protein to bind the ribosome,
      resulting in vivo in a reduced ability of Sup45p to release nascent polypeptides
      from the ribosome at the non-permissive temperature. Cell-free translation
      lysates from the sup45-2 strain do not show a defect in sense-codon translation
      at the non-permissive temperature. These data demonstrate that yeast eRF1 plays a
      role in translation termination and is functionally equivalent to its higher
      eukaryotic homologues.

PMID- 9182991
TI  - Identification of an RNA-binding-loop in the N-terminal region of signal
      recognition-particle protein SRP19.
AB  - Protein SRP19 is a 144-amino-acid polypeptide that associates intimately with the
      signal-recognition particle RNA (SRP RNA) and serves as an important structural
      and functional component of the SRP. We investigated the structure and RNA
      binding activity of the human SRP19 protein by the use of comparative sequence
      analysis, high-stringency structure prediction, proteolytic susceptibility, and
      site-directed mutagenesis. SRP19 was found to consist of two distinct regions
      (called N-terminal and C-terminal regions) that are separated by a boundary of
      approximately 12-15 amino acid residues. Both regions contain an alpha-helix and
      several beta-strands that are connected by loops or turns. In agreement with the
      hypothetical model, proteolytic susceptibility demonstrated the predominant
      accessibility of two sites: one in a surface loop of the N-terminal region
      (YLNNKKTIAEGR33), and another site in the C-terminal tail at residues L129 and
      E133. The RNA-binding activities of mutant polypeptides with changes of conserved
      lysines and arginines (mutants K27Q, R33Q and R34Q) demonstrated that the
      proteolytically accessible loop of the N-terminal region is in direct contact
      with the SRP RNA. In contrast, alteration of a certain basic amino acid residues
      in the C-terminal region (R83, K116 and R118), as well as a deletion of four
      amino acid residues located at the boundary between the two regions, had no
      effect on the RNA-binding ability. The structural model that emerges from our
      data is thematically similar to that of ribosomal protein S5, the N-domain of
      which contains a loop motif believed to interact with double-stranded RNA. The
      presence of a similar structural feature in protein SRP19 has significant
      implications for the structure and function of the SRP19-RNA complex.

PMID- 9182992
TI  - Identification of amino acids of endonuclease VII essential for binding and
      cleavage of cruciform DNA.
AB  - Endonuclease VII is a Holliday-structure-resolving enzyme of bacteriophage T4.
      The active protein is a homodimer with 157 amino acids/monomer. An amber mutation
      (amE727 in codon 151) inactivates the nuclease completely, indicating the
      importance of the seven C-terminal amino acids for nucleolytic activity. The
      influence of these amino acids on cruciform-DNA binding and cleavage was
      investigated through functional analysis of C-terminal-truncated proteins derived
      from deletion constructs. It was found that the three C-terminal amino acids are
      not necessary for binding and cleavage. A transition from active to inactive
      protein occurs gradually with truncations of the next four amino acids. Reduction
      of DNA-binding ability, as measured by electrophoretic mobility shift assays, was
      determined to be the primary defect in the cleavage-deficient proteins. This was
      further concluded by the finding that EVII-(1-150)-peptide(amber), a protein with
      fairly low affinity to cruciform DNA, contributes cleavage activity to reactions
      of wild-type EVII with cruciform DNA. [Asp62]EVII-(1-156)-peptide lacking one C
      terminal amino acid, contains a point mutation in codon 62 that eliminates the
      nucleolytic activity of the protein while retaining its DNA-binding proficiency.
      By mixing binding-deficient and cleavage-deficient mutants in the same assay,
      cleavage of cruciform DNA resumed. Evidence is presented that complementation
      occurs by heterodimer formation. Our results show that the zinc-binding motif of
      EVII is not sufficient for cruciform-DNA binding.

PMID- 9182993
TI  - Secondary structure and tertiary fold of the human immunodeficiency virus protein
      U (Vpu) cytoplasmic domain in solution.
AB  - The human immunodeficiency virus type 1 Vpu protein enhances virus particle
      release from infected cells, decreases the tendency of syncytia formation and
      induces degradation of human CD4 receptor. It is known that the cytoplasmic part
      of Vpu is responsible for direct interaction to and degradation of CD4. The
      tertiary fold of the Vpu cytoplasmic domain in aqueous solution was determined
      employing NMR spectroscopy and molecular-dynamics simulated-annealing protocols.
      We found a very well defined amphipathic alpha-helix in the membrane proximal
      part (40-50), a less well defined helix (60-68), and a short alpha-helix at the C
      terminus (75-79). We further determined the overall tertiary structure based on
      long-range nuclear Overhauser enhancement effects. Correlation of results from
      mutation experiments of Vpu and the structure data is discussed.

PMID- 9182994
TI  - Addition of acetaldehyde to the N-terminus of a recombinant Schistosoma mansoni
      glutathione S-transferase upon high-level expression in Saccharomyces cerevisiae.
AB  - Intracellular expression of recombinant Schistosoma mansoni protein p28 (Smp28)
      in soluble form to a concentration of more than 6 g/l culture in Saccharomyces
      cerevisiae was accompanied by a post-translational modification, which occurred
      during the late stage of the culture. The modified protein, which had a reduced
      isoelectric point, was isolated by anion-exchange HPLC and characterized by
      tryptic mapping by means of on-line reversed-phase HPLC/electrospray mass
      spectrometry. Comparison with non-modified recombinant Smp28 allowed us to
      localize the modification to the N-terminal hexapeptide AGEHIK, which had an
      increased mass of 26 Da. Reversed-phase HPLC of the modified peptide with a
      shallow acetonitrile gradient revealed the presence of two components of
      identical mass and amino acid composition. Both peptides were inaccessible to N
      terminal Edman sequencing, indicating that a rearrangement of the N-terminal
      region of recombinant Smp28 had taken place during tryptic digestion leading to
      two isomeric, N-terminally blocked peptides. Deuterium-exchange mass spectrometry
      showed that the modified peptides lacked two exchangeable protons, suggesting
      cyclic modifications implying the N-terminal amino group. Tandem mass
      spectrometry by means of the nano-electrospray technique and collision-induced
      dissociation allowed us to identify the modified sites as Ala1, His4 and Lys6
      based on a characteristic modified a1 ion of Ala1 (70.0 Da), a modified immonium
      ion of His4 (136.0 Da) and a modified y1" ion (173.2 Da) of Lys6. Combination of
      all the above results led to the conclusion that recombinant Smp28 was initially
      modified at its N-terminus by addition of acetaldehyde to form an aldimine which
      rearranged during tryptic digestion to two different cyclic peptides.

PMID- 9182995
TI  - Characterization of human and pig kidney long-chain-acyl-CoA dehydrogenases and
      their role in beta-oxidation.
AB  - Long-chain-acyl-CoA dehydrogenase (LCADH) has been produced by recombinant
      techniques from the human cDNA and purified after expression in Escherichia coli.
      Pig kidney LCADH was purified using an optimized method which also produces
      apparently pure short-chain-acyl-CoA dehydrogenase (SCADH) and medium-chain-acyl
      CoA dehydrogenase (MCADH) in good yields. LCADH from both sources has a maximal
      turnover rate (Vmax of 650-700 min(-1) at pH 7.6) with the best substrates, which
      is approximately fivefold higher than reported previously. The human enzyme has
      an approximately fivefold higher Km compared with the pig kidney enzyme with
      substrates of chain length from C10 to C18 and a significantly different
      dependence of Vmax on the chain length. Pig kidney LCADH has a similar Vmax/Km
      with C10 to C14 substrates as MCADH does with C6 to C10 substrates. Recombinant
      human LCADH, however, is significantly less efficient (approximately fourfold
      with C12) than purified pig kidney enzyme. We conclude that human LCADH is either
      quantitatively less important in beta-oxidation than in the pig, or that post
      translational modifications, not present in the recombinant human enzyme, are
      required to optimize human LCADH activity. Our results demonstrate that LCADH is
      as important as the other acyl-CoA dehydrogenases in fatty acid oxidation at
      physiological, mitochondrial pH with optimal substrates of chain length C10-C14.
      The extent of the LCADH-flavin cofactor reduction observed with most substrates
      and the rate of the subsequent reoxidation with oxygen are markedly different
      from those found with human medium chain acyl-CoA dehydrogenase. Both LCADH are
      inactivated by the substrate analogue 2-octynoyl-CoA, possibly via covalent
      modification of Glu261, the active-site residue involved in deprotonation of the
      substrate (alpha)C-H.

PMID- 9182996
TI  - A kinetic model for the interaction of nitric oxide with a mammalian
      lipoxygenase.
AB  - Nitric oxide (NO) has been known for a long while to act as an inactivator of the
      soybean lipoxygenase-1 and cyclooxygenase. More recently, NO was shown to
      interact also with a mammalian 15-lipoxygenase [Wiesner, R., Rathmann, J.,
      Holzhutter, H. G., Stosser, R., Mader, K., Nolting, H. & Kuhn, H. (1996) Nitric
      oxide oxidises ferrous mammalian lipoxygenases to a pre-activated ferric species,
      FEBS Lett. 389, 229-232]. In this paper we present a detailed kinetic analysis of
      the interaction of NO with the 15-lipoxygenase from reticulocytes. Time courses
      of hydroperoxide formation were monitored after an anaerobic incubation of the
      enzyme with varying concentrations of NO and for varying length of the incubation
      period. Owing to the presence of O2 during the enzymatic reaction, the inhibitory
      effect of NO declines in a time-dependent manner since NO is converted into non
      reactive NO2. This is manifested as a lag phase of the time course. The lag phase
      becomes more pronounced if the enzyme is incubated over a fixed period (15 s)
      with increasing concentrations of NO. In contrast, increasing the length of the
      incubation period at fixed concentrations of NO diminishes the duration of the
      lag phase. These experimental findings can be accounted for by a kinetic model
      which assumes (a) fast reversible binding of NO to the inactive ferrous Fe(II)
      form of the enzyme and (b) slow irreversible conversion of the Fe(II)-NO complex
      into an activated ferric form of the enzyme which is susceptible to peroxide
      activation. The rate constants for these two different kinetic modes of NO action
      were estimated by fitting the solutions of the model equations to the
      experimental time courses. The dissociation constant of the Fe(II)-NO complex
      amounts to 2.5 microM. Computer simulations performed on the basis of the model
      indicate that the response of the lipoxygenase to increasing intracellular NO
      concentrations depend upon the available peroxide tone: at low peroxide
      concentration the enzyme is initially trapped in the inactive ferrous form and
      thus may be activated by NO via the activated ferric species. On the other hand,
      at high peroxide concentrations, a partial inhibition of the initially active
      enzyme is expected.

PMID- 9182997
TI  - Structural characterization of N-linked oligosaccharides from cellobiohydrolase I
      secreted by the filamentous fungus Trichoderma reesei RUTC 30.
AB  - We have characterized the primary structures of the predominant N-linked
      oligosaccharides on cellobiohydrolase I from the filamentous fungus Trichoderma
      reesei RUTC30. Different enzymatic and chromatographic techniques were used to
      analyze six oligosaccharides. The combined data showed that the fungal
      carbohydrates have a core structure that is identical to the mammalian N-linked
      core. In the bulk of the N-glycans, the alpha-1,3 arm is extended with two
      mannoses and a glucose, suggesting incomplete processing of the oligosaccharides
      in the endoplasmic reticulum. The alpha-1,6 arm shows a remarkable heterogeneity:
      in addition to alpha-1,2-Man and alpha-1,6-Man, the presence of a terminal
      mannose alpha-1,6-phosphodiester was observed. This latter substituent has not
      been characterized before on mannosidase-processed N-glycan and its function and
      synthesis pathway are entirely unknown. The predominant N-glycans on
      cellobiohydrolase I can be represented as follows: GlcMan8GlcNAc2,
      GlcMan7GlcNAc2, Man7GlcNAc2, ManPGlcMan7GlcNAc2, GlcMan5GlcNAc2 and Man5GlcNAc2.

PMID- 9182998
TI  - The two facies of pyrrolizidine alkaloids: the role of the tertiary amine and its
      N-oxide in chemical defense of insects with acquired plant alkaloids.
AB  - Larvae of Creatonotos transiens (Lepidoptera, Arctiidae) and Zonocerus variegatus
      (Orthoptera, Pyrgomorphidae) ingest 14C-labeled senecionine and its N-oxide with
      the same efficiency but sequester the two tracers exclusively as N-oxide. Larvae
      of the non-sequestering Spodoptera littoralis eliminate efficiently the ingested
      alkaloids. During feeding on the two alkaloidal forms transient levels of
      senecionine (but not of the N-oxide) are built up in the haemolymph of S.
      littoralis larvae. Based on these results, senecionine [18O]N-oxide was fed to C.
      transiens larvae and Z. variegatus adults. The senecionine N-oxide recovered from
      the haemolymph of the two insects shows an almost complete loss of 18O label,
      indicating reduction of the orally fed N-oxide in the guts, uptake of the
      tertiary alkaloid and its re-N-oxidation in the haemolymph. The enzyme
      responsible for N-oxidation is a soluble mixed function monooxygenase. It was
      isolated from the haemolymph of the sequestering arctiid Tyria jacobaeae and
      purified to electrophoretic homogeneity. The enzyme is a flavoprotein with a
      native Mr of 200000 and a subunit Mr of 51000. It shows a pH optimum at 7.0, has
      its maximal activity at a temperature of 40-45 degrees C and an isoelectric point
      at pH 4.9. The reaction is strictly NADPH-dependent (Km 1.3 microM). From 20
      pyrrolizidine alkaloids so far tested as substrates, the enyzme N-oxidizes only
      alkaloids with structural elements which are essential for hepatotoxic and
      genotoxic pyrrolizidine alkaloids (i.e. 1,2-double bond, esterification of the
      allylic hydroxyl group, presence of a second free or esterified hydroxyl group at
      carbon 7). A great variety of related alkaloids and xenobiotics were tested as
      substrate, none was accepted. The Km values of senecionine, monocrotaline and
      heliotrine, representing the three main types of pyrrolizidine alkaloids, are 1.3
      microM, 12.5 microM and 290 microM, respectively. The novel enzyme was named
      senecionine N-oxygenase (SNO). The enzyme was partially purified from two other
      arctiids. The three SNOs show the same general substrate specificity but differ
      in their affinities towards the main structural types of pyrrolizidine alkaloids.
      The enzymes from the two generalists (Creatonotos transiens and Arctia caja)
      display a broader substrate affinity than the enzyme from the specialist (Tyria
      jacobaeae). The two molecular forms of pyrrolizidine alkaloids, the lipophilic
      protoxic tertiary amine and its hydrophilic nontoxic N-oxide are discussed in
      respect to their bioactivation and detoxification in mammals and their role as
      defensive chemicals in specialized insects. Pyrrolizidine-alkaloid-sequestering
      insects store the alkaloids as nontoxic N-oxides which are reduced in the guts of
      any potential insectivore. The lipophilic tertiary alkaloid is absorbed passively
      and then bioactivated by cytochrome P-450 oxidase.

PMID- 9182999
TI  - The O-specific polysaccharide chain of Campylobacter fetus serotype A
      lipopolysaccharide is a partially O-acetylated 1,3-linked alpha-D-mannan.
AB  - A polysaccharide fraction liberated from Campylobacter fetus subsp. fetus
      serotype A lipopolysaccharide by mild acid hydrolysis followed by gel-permeation
      chromatography contained a partially O-acetylated D-mannan chain, as an O
      specific polysaccharide, with a core oligosaccharide attached. The structure of
      the polysaccharide was studied by O-deacetylation, methylation, and 1H- and 13C
      NMR spectroscopy, including computer-assisted analysis of the 13C-NMR spectrum. A
      structure of -->3)-alpha-D-Manp2Ac-(1--> was established as the structure of the
      O-specific polysaccharide, the degree of O-acetylation of the mannose residues at
      position 2 being estimated as 80-90%. As judged by the ratio of mannose to core
      constituents, the D-mannan chain consists on average of 10-12 monosaccharide
      units.

PMID- 9183000
TI  - Role of the carboxy-terminal domain of human apolipoprotein AI in high-density
      lipoprotein metabolism--a study based on deletion and substitution variants in
      transgenic mice.
AB  - Cholesterol levels in high-density lipoprotein (HDL) of transgenic mice
      overexpressing human apolipoprotein AI (apoAI), a des-(190-243)-apoAI deletion
      mutant or an apoAI-(1-189)-apoAII-(12-77) chimera were 2.8-fold (P<0.001), 1.3
      fold (P<0.05) and 2.2-fold (P<0.001) higher than in control mice, respectively.
      Human apolipoprotein levels in apoAI and in apoAI-(1-189)-apoAII-(12-77)
      transgenic mice were 5.2-fold and 3.5-fold higher than in des-(190-243)-apoAI
      transgenic mice, whereas their HDL cholesterol levels were 2.1-fold and 1.6-fold
      higher. PAGE of HDL isolated by ultracentrifugation revealed that murine HDL
      migrated as 9.6-nm and 7.2-nm particles. Overexpression of human apoAI and apoAI
      (1-189)-apoAII-(12-77) resulted in the production of polydisperse HDL (9.6, 9.2,
      8.4 and 7.2 nm) particles, whereas overexpression of des-(190-243)-apoAI
      primarily resulted in an increase of 7.2-nm particles. The fractional catabolic
      rates of human apoAI and apoAI-(1-189)-apoAII-(12-77) were very similar, whereas
      that of des-(190-243)-apoAI was 4.9-fold higher. The endogenous production rates
      of human apoAI, des-(190-243)-apoAI and apoAI-(1-189)-apoAII-(12-77) in
      transgenic mice were very similar. It is concluded that deletion of the carboxy
      terminal domain of apoAI reduces its lipoprotein association, resulting in the
      production of small, phospholipid-rich HDL particles that are cleared more
      rapidly. Substitution of the carboxy-terminal helices of apoAI with helices of
      apoAII restores lipoprotein association, resulting in the production of HDL,
      which migrates as human HDL3 and HDL2. Although the carboxy-terminal domain of
      the chimera contained more than 80% of the amino acid sequence of apoAII, its HDL
      distribution profile in transgenic mice was very similar to that of human apoAI.
      This study demonstrates the importance of the helical structure of apoAI of the
      carboxy-terminal domain of apoAI, rather than of its exclusive amino acid
      sequence, in HDL metabolism.

PMID- 9183001
TI  - Elderberry (Sambucus nigra) bark contains two structurally different
      Neu5Ac(alpha2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins.
AB  - A second NeuAc(alpha2,6)Gal/GalNAc binding type 2 ribosome-inactivating protein
      (RIP), called SNAI' has been isolated from elderberry (Sambucus nigra) bark.
      SNAI' is a minor bark protein which closely resembles the previously described
      major Neu5Ac(alpha2,6)Gal/GalNAc binding type 2 RIP called SNAI with respect to
      its carbohydrate-binding specificity and ribosome-inactivating activity but has a
      different molecular structure. Molecular cloning revealed that the deduced amino
      acid sequence of SNAI' is highly similar to that of SNAI and that the difference
      in molecular structure between both proteins relies on a single cysteine residue
      present in the B chain of SNAI but absent from SNAI'. The isolation of SNAI' not
      only identifies a minor bark protein as a type 2 RIP but also further emphasizes
      the complexity of the type 2 RIP/lectin mixture present in the bark of
      elderberry.

PMID- 9183002
TI  - Evaluation of subunit truncation and the nature of the spacer for single chain
      human gonadotropins.
AB  - Three single chain gonadotropins were designed based on the three-dimensional
      structure of human choriogonadotropin and structure/activity relationships of the
      glycoprotein hormones. In each single chain, the C-terminal end of the human
      choriogonadotropin beta subunit is connected via Ser-Gly repeats to the N
      terminal end of the alpha subunit. In addition, two of the single chains have
      truncated subunits. The three mutants were expressed in CHO cells. In vitro
      binding of two of the three mutants to the human lutropin/choriogonadotropin
      receptor was found to be comparable to wild-type lutropin. In contrast, both the
      receptor binding and the in vitro bioactivity of the mutant with truncated alpha
      and beta subunits in which the beta:26-110 disulphide bond cannot be formed, are
      lowered relative to wild-type lutropin. The fact that this mutant still displays
      biological activity shows that the seat-belt arrangement proposed by Isaacs and
      coworkers [Lapthorn, A. J., Harris, D. C., Littlejohn, A., Lustbader, J. W.,
      Canfield, R. E., Machin, K. J.. Morgan, F. J. & Isaacs, N. W. (1994) Nature 369,
      455-461] is important but not essential for receptor binding and biological
      activity in the context of single chain gonadotropins. Single chains in which Ser
      Gly spacers are combined with truncated subunits, provide an attractive approach
      towards the design and generation of novel, biologically active gonadotropins.

PMID- 9183003
TI  - Inhibition of human placenta glutathione transferase P1-1 by the antibiotic
      calvatic acid and its diazocyanide analogue--evidence for multiple catalytic
      intermediates.
AB  - The inhibition mechanism of the dimeric human placenta glutathione transferase
      (GST) P1-1 by calvatic acid and the reaction intermediates, i.e. the diazocyanide
      analogue of calvatic acid, has been investigated at pH 7.0 and 30.0 degrees C.
      Experiments performed at different molar ratios of inhibitor/GST P1-1 indicate
      that 1 mol calvatic acid inactivates 1 mol GST P1-1, containing two catalytically
      equivalent active sites. However, 2 mol of the diazocyanide analogue of calvatic
      acid inactivate 1 mol GST P1-1. Two disulfide bridges/dimer, probably between
      Cys47 and Cys101, have been formed during the reaction of GST P1-1 with calvatic
      acid and its diazocyanide analogue. The apparent second-order rate constants for
      GST P1-1 inactivation by calvatic acid and its diazocyanide analogue are 2.4+/
      0.3 M(-1) s(-1) and (8.5+/-0.7) x 10(3) M(-1) s(-1), respectively. The reaction
      of calvatic acid with free L-cysteine can be described by a simple process with
      an apparent second-order rate constant of (5.0+/-0.4) x 10(1) M(-1) s(-1). In
      contrast, a transient species occurs during the reaction of the diazocyanide
      analogue of calvatic acid with free L-cysteine. Kinetics may be described by a
      second-order process [the rate constant being (8.0+/-0.5) x 10(3) M(-1) s(-1)]
      followed by a first-order decay [the rate constant corresponding to (1.2+/-0.1) x
      10(1) s(-1)]. Calvatic acid represents an enzyme inhibitor acting much slower
      than its reaction intermediates (i.e. its diazocyanide analogue).

PMID- 9183004
TI  - Structural studies of the O-specific chains of Hafnia alvei strains 744, PCM 1194
      and PCM 1210 lipopolysaccharides.
AB  - The structures of the O-specific chains of the Hafnia alvei strain 744 and PCM
      strains 1194 and 1210 lipopolysaccharides have been investigated. Methylation
      analysis, dephosphorylation, NMR spectroscopy, matrix-assisted laser-desorption
      ionisation time-of-flight mass spectrometry and fast-atom-bombardment mass
      spectrometry were the principal methods used. It was concluded that the
      polysaccharides of strains 744 and PCM 1194 are composed of the same
      pentasaccharide repeating unit having the following structure: [structure in
      text] and that the polysaccharide of strain PCM 1210 is composed of a
      pentasaccharide repeating unit having the following structure: [structure in
      text].

PMID- 9183005
TI  - Prothrombin, albumin and immunoglobulin A form covalent complexes with alpha1
      microglobulin in human plasma.
AB  - Molecules containing the 33-kDa plasma protein alpha1-microglobulin were isolated
      from human plasma by anti-(alpha1-microglobulin) affinity chromatography. Five
      major bands could be seen after electrophoretic separation of the alpha1
      microglobulin-containing proteins under native conditions. Immunoblotting
      demonstrated alpha1-microglobulin in all five bands. Two of these have been
      described previously: free alpha1-microglobulin and alpha1-microglobulin
      complexed with IgA (IgA x alpha1-microglobulin). The other three bands were
      identified as prothrombin alpha1-microglobulin, albumin x alpha1-microglobulin
      and dimeric alpha1-microglobulin. Prothrombin x alpha1-microglobulin were 1:2 and
      1:1 complexes which carried approximately 1% of total alpha1-microglobulin, had
      molecular masses of about 145 kDa and 110 kDa upon SDS/PAGE and dissociated
      completely to free alpha1-microglobulin and prothrombin (72 kDa) when reducing
      agents were added, suggesting that the complexes were stabilized by disulfide
      bonds. The alpha1-microglobulin molecules did not inhibit cleavage of prothrombin
      by factor Xa and were bound to the peptides which were released upon activation
      of prothrombin. Albumin x alpha1-microglobulin, corresponding to 7% of total
      plasma alpha1-microglobulin, was a mixture between 1:1 and 1:2 complexes, with
      masses upon SDS/PAGE of approximately 100 kDa and 135 kDa, respectively. Both
      these complexes dissociated only partially to free alpha1-microglobulin and
      albumin when reducing agents were added. The albumin x alpha1-microglobulin
      complexes carried a yellow-brown chromophore similar to free alpha1
      microglobulin. The complex-binding to alpha1-microglobulin did not block the
      fatty-acid-binding ability of albumin. The plasma concentrations of albumin x
      alpha1-microglobulin and prothrombin x alpha1-microglobulin were estimated to 5.2
      mg/l and 1.1 mg/l, respectively.

PMID- 9183006
TI  - The in vitro phosphorylation of p53 by calcium-dependent protein kinase C-
      characterization of a protein-kinase-C-binding site on p53.
AB  - We show that, in vitro, Ca2+-dependent protein kinase C (PKC) phosphorylates
      recombinant murine p53 protein on several residues contained within a conserved
      basic region of 25 amino acids, located in the C-terminal part of the protein.
      Accordingly, synthetic p53-(357-381)-peptide is phosphorylated by PKC at multiple
      Ser and Thr residues, including Ser360, Thr365, Ser370 and Thr377. We also
      establish that p53-(357-381)-peptide at micromolar concentrations has the ability
      to stimulate sequence-specific DNA binding by p53. That stimulation is lost upon
      phosphorylation by PKC. To further characterise the mechanisms that regulate PKC
      dependent phosphorylation of p53-(357-381)-peptide, the phosphorylation of
      recombinant p53 and p53-(357-381)-peptide by PKC were compared. The results
      suggest that phosphorylation of full-length p53 on the C-terminal PKC sites is
      highly dependent on the accessibility of the phosphorylation sites and that a
      domain on p53 distinct from p53-(357-381)-peptide is involved in binding PKC.
      Accordingly, we have identified a conserved 27-amino-acid peptide, p53-(320-346)
      peptide, within the C-terminal region of p53 and adjacent to residues 357-381
      that interacts with PKC in vitro. The interaction between p53-(320-346)-peptide
      and PKC inhibits PKC autophosphorylation and the phosphorylation of substrates,
      including p53-(357-381)-peptide, neurogranin and histone H1. Conventional Ca2+
      dependent PKC alpha, beta and gamma and the catalytic fragment of PKC (PKM) were
      nearly equally susceptible to inhibition by p53-(320-346)-peptide. The Ca2+
      independent PKC delta was much less sensitive to inhibition. The significance of
      these findings for understanding the in vivo phosphorylation of p53 by PKC are
      discussed.

PMID- 9183007
TI  - Kinetic analysis of two closely related receptor-like protein-tyrosine
      phosphatases, PTP alpha and PTP epsilon.
AB  - Among transmembrane protein-tyrosine-phosphatases, the membrane distal catalytic
      domain (D2) of protein-tyrosine-phosphatase alpha (PTP alpha) is unusual in
      having low but detectable activity in the absence of the membrane proximal
      catalytic domain (D1). To investigate the catalytic properties of PTP alpha D2 in
      association with D1, kinetic parameters of activity were established for PTP
      alpha D1D2 proteins containing an inactivating point mutation in D1 and/or D2. In
      this context, D2 activity was unchanged by the presence (N-terminal or C
      terminal) or absence of inactive D1, and the presence or absence of inactive D2
      affected the velocity but not the Km of D1 catalysis. While D1 appears to be the
      major catalytic contributor to PTP alpha activity, D2 possesses a significantly
      higher substrate-specific activity relative to wild-type D1D2 than the D2 domains
      of other protein-tyrosine-phosphatases. Also, PTP alpha D2 is an active
      phosphatase with comparable or better efficiency, on the basis of k(cat)/Km
      criteria, to some of the dual specificity phosphatases. Kinetic parameters of a
      closely related receptor-like protein-tyrosine-phosphatase, PTP epsilon, were
      determined. PTP epsilon D1 is the major, if not the only, catalytic moiety of PTP
      epsilon, and has much higher turnover numbers than D1 of PTP alpha. The PTP
      epsilon D2 activity is insignificant compared to that of PTP epsilon-D1D2, with
      lower turnover numbers than PTP alpha D2. Thus, the intrinsic activity of PTP
      alpha D2 is high compared to other D2 domains and, more outstandingly, its
      activity relative to D1 appears unique. These are also apparent upon in vitro
      assay of full-length PTP alpha catalytic mutants expressed in mammalian cells.
      Together. these results suggest potential catalytic and regulatory roles for PTP
      alpha D2, and that PTP alpha may be an optimal model transmembrane protein
      tyrosine-phosphatase for investigating the former within the cell.

PMID- 9183008
TI  - Specific stimulation of c-Fgr kinase by tyrosine-phosphorylated (poly)peptides-
      possible implication in the sequential mode of protein phosphorylation.
AB  - Hematopoietic lineage cell-specific HS1 protein is converted into a substrate for
      c-Fgr by previous Syk-mediated phosphorylation, at site(s) that bind to the SH2
      domain of c-Fgr [Ruzzene, M., Brunati, A. M., Marin, O., Donella-Deana, A. &
      Pinna, L. A. (1996) Biochemistry 35, 5327-5332]. Here we show that a
      phosphopeptide derived from one such site, HS1-(320-329)-phosphopeptide
      (PEGDYpEEVLE), enhances up to tenfold, in a dose-dependent manner, the catalytic
      activity of c-Fgr either assayed with peptide substrates or evaluated as
      intermolecular autophosphorylation of c-Fgr itself. The dephosphorylated HS1-(320
      329)-peptide is totally ineffective, while the stimulatory efficacy of other
      phosphopeptides derived from the polyoma virus middle T antigen-(393-402)
      sequence, c-Src, and c-Fgr autophosphorylation sites, and the C-terminal c-Src
      site (Tyr527) is variable and correlates reasonably well with the predicted
      affinity for the c-Fgr SH2 domain. Stimulation of c-Fgr catalytic activity is
      also promoted by the full-length HS1 protein, previously tyrosine phosphorylated
      by Syk, and is accounted for by an increased Vmax while the Km values are
      unchanged. If the normal activator of c-Fgr kinase, Mg2+, is replaced by Mn2+,
      stimulation by HS1-(320-329)-phosphopeptide is still observable with peptide
      substrates, while autophosphorylation is, in contrast, inhibited by the
      phosphopeptide. These findings, in conjunction with the ability of previously
      autophosphorylated c-Fgr to be stimulated by HS1-(320-329)-phosphopeptide,
      support the view that stimulation of c-Fgr by phosphopeptide is not or is not
      entirely a consequence of increased autophosphorylation. Interestingly, neither
      Syk and C-terminal Src kinase nor three other members of the Src family (Lyn,
      Lck, and Fyn) are susceptible to stimulation by phosphopeptide, as observed with
      c-Fgr. These data support the notion that c-Fgr undergoes a unique mechanism of
      activation promoted by tyrosine-phosphorylated polypeptide that binds to its SH2
      domain. This suggests that such a mode of regulation is peculiar of protein
      tyrosine kinases committed to the secondary phosphorylation of sequentially
      phosphorylated proteins.

PMID- 9183009
TI  - Molecular cloning and nucleotide sequence of an endo-1,5-alpha-L-arabinase gene
      from Bacillus subtilis.
AB  - The nucleotide sequence of the gene encoding an endo-1,5-alpha-L-arabinase
      (protopectinase C) of Bacillus subtilis was determined by sequencing fragments
      amplified by the cassette-ligation-mediated PCR (CLM-PCR). The gene covering the
      start and stop codon was amplified by PCR with two specific primers, which were
      designed from the sequence data determined by CLM-PCR. An approximately 1.5-kb
      amplification product was cloned into the vector pUC119, forming a plasmid termed
      pPPC. An ORF that encodes the arabinase composed of 324 amino acids including a
      33-amino-acid signal peptide was assigned. Comparison of the deduced amino acid
      sequence of the enzyme with that of an Aspergillus niger endoarabinase showed 37%
      identity in a 207-amino-acid overlap. The optimal nucleotide sequence for
      catabolite repression of B. subtilis was found upstream of the structural gene.
      In a culture of Escherichia coli DH5alpha cells harboring pPPC, no arabinase
      activity was detected, either intracellularly or extracellularly, suggesting that
      the B. subtilis promotor is not functional in this transformant. In B. subtilis
      IFO 3134 strain, production of protopectinase C was repressed by readily
      metabolizable carbohydrates. In contrast, productivity (total enzyme
      activity/bacterial growth) of the enzyme was increased about fourfold in the
      presence of 0.75 M potassium phosphate in the culture medium. The phosphate anion
      seemed to be involved in the stimulation of protopectinase C production in this
      stain.

PMID- 9183010
TI  - Thermochemical and kinetic evidence for nucleotide-sequence-dependent RecA-DNA
      interactions.
AB  - RecA catalyses homologous recombination in Escherichia coli by promoting pairing
      of homologous DNA molecules after formation of a helical nucleoprotein filament
      with single-stranded DNA. The primary reaction of RecA with DNA is generally
      assumed to be unspecific. We show here, by direct measurement of the interaction
      enthalpy by means of isothermal titration calorimetry, that the polymerisation of
      RecA on single-stranded DNA depends on the DNA sequence, with a high exothermic
      preference for thymine bases. This enthalpic sequence preference of thymines by
      RecA correlates with faster binding kinetics of RecA to thymine DNA. Furthermore,
      the enthalpy of interaction between the RecA x DNA filament and a second DNA
      strand is large only when the added DNA is complementary to the bound DNA in
      RecA. This result suggests a possibility for a rapid search mechanism by RecA x
      DNA filaments for homologous DNA molecules.

PMID- 9183011
TI  - The N-domain of the signal recognition particle 54-kDa subunit promotes efficient
      signal sequence binding.
AB  - The signal recognition particle 54-kDa subunit (SRP54) binds to the signal
      sequences of nascent presecretory and transmembrane proteins. Previous studies
      have shown that signal sequences bind to the C-terminal methionine-rich domain of
      the protein (M-domain), but have raised the possibility that either the N
      terminal domain (N-domain) or the central guanosine triphosphatase module (GTPase
      domain) also contribute to signal-sequence-binding activity. We have generated a
      series of N-domain and GTPase-domain mutants to investigate this issue further.
      Mutations in a conserved N-domain motif (ALLEADV) produced significant defects in
      signal sequence binding that correlate with the severity of the mutation. The
      magnitude of the defect was independent of the preprotein substrate, which
      suggested that the mutations do not alter the specificity of signal sequence
      recognition. The N-domain mutants also showed defects in promoting the
      translocation of presecretory proteins across the membrane of microsomal
      vesicles, but these defects appeared to be a direct consequence of the reduction
      in signal-sequence-binding activity and not separate effects of the mutations. By
      contrast, mutations in the guanosine triphosphatase consensus sequence had no
      effect on signal sequence binding, but instead severely impaired protein
      translocation activity. These results indicate that a principal function of the
      SRP54 N-domain is to promote efficient signal sequence binding. These data also
      suggest that the SRP54 GTPase regulates the cycle of signal sequence binding and
      release, perhaps by modulating the relative orientation of the N- and M-domains.

PMID- 9183012
TI  - Redox-mediated regulation of p21(waf1/cip1) expression involves a post
      transcriptional mechanism and activation of the mitogen-activated protein kinase
      pathway.
AB  - p21(waf1/cip1) gene expression is induced by DNA damage in cells with wild-type
      p53 and contributes to the arrest of cell growth. It was demonstrated that under
      many experimental conditions, including oxidative stress, p21(waf1/cip1)
      expression can be induced through p53-independent pathways. Since most of these
      experimental conditions induce the phosphorylation of mitogen-activated protein
      kinase (MAPK) and thus its activation, we evaluated p21(waf1/cip1) mRNA levels in
      cells exposed to an oxidative stress, induced by diethylmaleate (Et2Mal), and in
      which the MAPK pathway was blocked. The expression of a dominant-negative mutant
      of MEK, the MAPK kinase that phosphorylates and activates MAPK, and of a dominant
      negative [Asn17]Ras mutant prevented the Et2Mal-induced accumulation of
      p21(waf1/cip1) mRNA. Similarly, the expression of MEK- and of [Asn17]Ras mutants
      decreased the 12-O-tetradecanoyl-phorbol 13-acetate (TPA)-mediated p21(waf1/cip1)
      induction. Furthermore, TPA-induced and serum-induced p21(waf1/cip1) mRNA
      accumulation was blocked by pretreating the cells with the antioxidant compound N
      acetylcysteine, suggesting that oxidative stress is involved in these responses.
      p21(waf1/cip1) mRNA levels reached a maximum within 2 h of adding Et2Mal or TPA;
      however, the rate of transcription from a p21(waf1/cip1)-promoter construct did
      not increase during this period. In contrast, cells treated with actinomycin D
      show an increase of p21(waf1/cip1) mRNA stability after Et2Mal treatment. This
      result suggests that the increase in p21(waf1/cip1) mRNA at early times results
      from post-transcriptional regulatory events. Longer exposure to TPA may activate
      p21(waf1/cip1) gene transcription through an Sp1-dependent mechanism, while
      Et2Mal treatment gradually inhibits p21(waf1/cip1) gene transcription through
      oxidative changes that affect Sp1 binding to DNA.

PMID- 9183013
TI  - Characterization of the molecular-chaperone function of the heat-shock-cognate-70
      interacting protein.
AB  - A histidine-tagged form of the recently discovered molecular chaperone, 70-kDa
      heat-shock cognate (Hsc70)-interacting protein (Hip), has been expressed in
      Escherichia coli and purified to near homogeneity. This protein remains soluble
      when expressed in E. coli. Several important properties of this chaperone have
      been investigated. HPLC size-exclusion chromatography indicates that the
      chaperone forms a tetramer similar to what has been reported for the native
      protein from rat liver cytosol. The recombinant form of Hip did not catalyze the
      hydrolysis of ATP and ATP analogs, although fluorescence measurements indicated
      that the chaperone recognizes anthraniloyl-dATP, anthraniloyl-ADP, and 2'-O
      trinitrophenyl-ATP. The role of Hip as a molecular chaperone has been confirmed
      by its ability to strongly bind to the reduced, carboxymethylated form of alpha
      lactalbumin. This interaction is specific for non-native domains since native
      alpha-lactalbumin fails to interact with Hip. Fluorescence-anisotropy
      measurements indicate that reduced, carboxymethylated lactalbumin binds Hip with
      a Kd of 5 microM. Although Hip appears to be able to bind nucleotides and non
      native proteins, it is unable to facilitate the refolding of two denatured
      proteins, E. coli alkaline phosphatase and mitochondrial malate dehydrogenase.
      Hip inhibited the refolding of alkaline phosphatase and malic dehydrogenase.
      Inhibition occurred at near stoichiometric levels of Hip and could not be
      reversed by the addition of ATP. These results suggest that Hip may regulate the
      function of the Hsp70 molecular chaperone complex in vivo and play a critical
      role in protein folding in the eukaryotic cytoplasm.

PMID- 9183014
TI  - Drosophila laminin binds to mammalian nidogen and to heparan sulfate
      proteoglycan.
AB  - A Drosophila laminin that has the chain composition alpha5 beta1 gamma1, relative
      to mammalian laminins, bound human and mouse nidogen almost as strongly as mouse
      laminin-1 (alpha1 beta1 gamma1) in solid-phase assays, and had only a fourfold
      lower affinity in a radioligand competition test. This is due to a short, highly
      conserved sequence that occurs in both laminin gamma1 chains and which binds
      nidogen. When the single conservative amino acid difference between the two
      sequences (Tyr-->His) was introduced into the mouse laminin binding module gamma1
      III4 it failed to cause any change of binding. A high affinity between Drosophila
      laminin and mouse nidogen resulted in the formation of a stable complex in
      solution. Drosophila laminin also bound to the mouse heparan sulfate proteoglycan
      perlecan and the formation of this complex was inhibited by heparin, but not by
      chondroitin sulfate. In addition, a weaker connection between the core protein of
      mouse perlecan and Drosophila laminin can be mediated through nidogen. Elastase
      and other proteases degraded Drosophila laminin to a restricted number of larger
      fragments (40-300 kDa), almost all of which were bound to a heparin affinity
      column. Three fragments could be displaced at low salt concentration and were
      derived from the short arms of the Drosophila laminin, as shown by sequence
      analysis. A more strongly bound 50-kDa fragment apparently comprised the globular
      domains LG2 and LG3 derived from the C-terminal part of its alpha chain.
      Therefore, Drosophila laminin and mouse laminin-1 differ in certain aspects of
      protease stability and heparin-binding sites that, in part, can be attributed to
      their different alpha chains. The data suggest the existence of a nidogen analog
      and heparan sulfate proteoglycans in Drosophila, which remain to be identified.

PMID- 9183015
TI  - Phosphorylation and activation of cytosolic phospholipase A2 by 38-kDa mitogen
      activated protein kinase in collagen-stimulated human platelets.
AB  - Phosphorylation and activation of cytosolic phospholipase A2 (PLA2) can occur
      independently of the activation of 42/44-kDa mitogen-activated protein (MAP)
      kinase in human platelets. We have investigated the hypothesis that the stress
      activated p38 MAP kinase plays a role in the regulation of cytosolic PLA2. The
      specific inhibitor of p38 MAP kinase, SB 203580 [4-(4-fluorophenyl)-2-(4
      methylsulfinylphenyl)-5-(4-pyridyl) imidazole], completely blocked the collagen
      stimulated phosphorylation of cytosolic PLA2 in the presence of a cyclooxygenase
      blocker, and reduced the release of [3H]arachidonic acid by low concentrations of
      collagen. Stimulation of platelets with collagen (100 microg/ml) enhanced in
      vitro PLA2 activity of platelet lysates twofold over basal levels. In vitro PLA2
      activity was reduced to basal levels when platelets were stimulated in the
      presence of SB 203580, but not in the presence of an inhibitor of the kinase that
      activates p42/p44 MAP kinase. SB 203580 only partially inhibited phosphorylation
      of cytosolic PLA2 in platelets that had not been treated with a cyclooxygenase
      blocker indicating that secondary stimulation by thromboxane A2 induces cytosolic
      PLA2 phosphorylation, by kinase(s) other than p38 MAP kinase. Under these
      conditions, inhibition of p42/p44 MAP kinase did not result in a reduction of
      cytosolic PLA2 phosphorylation, which is in agreement with the results obtained
      in the presence of cyclooxygenase blockers. In contrast to collagen, both p38 MAP
      kinase and p42/p44 MAP kinase participated in the phosphorylation of cytosolic
      PLA2 in platelets stimulated by cross-linking of the low-affinity receptor for
      immune complexes, Fc gammaRIIA. The present results demonstrate an important role
      for p38 MAP kinase in the regulation of cytosolic PLA2 activity in collagen
      stimulated human platelets.

PMID- 9183016
TI  - Identification and characterisation of a sequence related to human sorbitol
      dehydrogenase.
AB  - The polyol pathway comprises the enzymes aldose reductase and sorbitol
      dehydrogenase which convert glucose to fructose via sorbitol. Accumulation of
      sorbitol within the cell has been suggested to contribute to the progression of
      secondary complications of diabetes. High levels of sorbitol accumulate within
      the cell due to inadequate regulation of blood glucose levels. It has also been
      suggested that polymorphism in either the aldose reductase or sorbitol
      dehydrogenase genes might contribute to sorbitol accumulation. The human sorbitol
      dehydrogenase gene (SORD) has been described previously and a range of putative
      polymorphic variants were identified. Further analysis of human SORD yeast
      artificial chromosome clones has now shown that there is a second SORD-like
      sequence in man, which is extremely similar in sequence to SORD itself and which
      also maps to chromosome 15. Detailed sequence analysis suggests that this SORD
      related gene cannot be expressed as a full-length sorbitol dehydrogenase
      isoenzyme. However, knowledge of the presence of this highly similar sequence in
      the human genome is essential to ensure that sequence variations identified
      during genetic analysis of SORD are not attributed to polymorphisms within that
      gene itself.

PMID- 9183017
TI  - Characterization of a promoter within the first intron of the human CD4 gene.
AB  - The CD4 molecule is subject to complex regulation during T cell differentiation
      and activation. The elements regulating CD4 gene expression have only partially
      been defined. In this report, we identified a promoter element located in the
      first intron of the CD4 gene. This promoter preferentially functions in T cell
      lines and is preferentially active in CD4+, CD8+ cells. These findings are
      similar to other systems in which multiple promoters define tissue- and
      developmental-specific patterns of expression. Through a series of deletions,
      electrophoretic mobility shift assays and exonuclease III protection assays, we
      localized the basal promoter element to a 32-bp fragment. This element lacks
      potential binding domains for myb and ets, both of which have previously been
      shown to be involved in the function of the 5' murine and human CD4 promoter, and
      this suggests the presence of a novel, T-cell-specific transcription factor.
      These results also suggest that the CD4 expression requires the use of multiple
      regulatory elements located throughout the CD4 gene.

PMID- 9183018
TI  - The prothoracicotropic hormone bombyxin has specific receptors on insect ovarian
      cells.
AB  - Bombyxin II, a product of the brain of the adult silkmoth, Bombyx mori, binds to
      ovarian cells of three different species of lepidoptera, i.e. B. mori (silkmoth),
      Samia cynthia ricini (ailanthus moth), and an ovarian cell line of Spodoptera
      frugiperda (Sf9) (fall armyworm). Crude Sf9 cell membrane preparations were used
      to show that the purported bombyxin receptor binds its ligand in a specific,
      saturable, and reversible manner. The dissociation constant of the bombyxin
      receptor complex is 260+/-90 pM. Quantitative binding studies and Scatchard
      analysis suggest that every Sf9 cell displays 20000 receptors on the surface. The
      cross-linked bombyxin-receptor ligand complex has an apparent molecular mass of
      about 300 kDa as determined by SDS/PAGE. Reduction causes the bombyxin receptor
      to dissociate into two subunits with molecular masses of 90 kDa and 116 kDa. The
      size and subunit structure of the putative bombyxin receptor on Sf9 cells show
      some similarities to the mammalian insulin receptor.

PMID- 9183019
TI  - Ionic-strength-dependent transition of hen egg-white lysozyme at low pH to a
      compact state and its aggregation on thermal denaturation.
AB  - Equilibrium acid-induced unfolding of hen egg-white lysozyme has been
      investigated by a combination of optical methods, size-exclusion chromatography,
      and differential scanning calorimetry. The results showed the presence of a
      partially folded state of hen egg-white lysozyme at pH 1.5, characterized by a
      substantial secondary structure, a large solvent exposure of non-polar clusters,
      and significantly disrupted tertiary structure. A large enthalpy was also
      associated with the conversion of the acid-unfolded state to a fully unfolded
      state. Size-exclusion chromatography and 8-anilino-1-naphthalenesulphonic acid
      binding studies showed an ionic-strength-induced transition of the partially
      folded state to a compact conformation. Furthermore, an ionic-strength-dependent
      aggregation on thermal unfolding of the partially folded intermediate was also
      observed. These observations provide insights into the possible features
      responsible for the stabilization of intermediates in the folding of hen egg
      white lysozyme.

PMID- 9183020
TI  - Purification and characterization of flavoproteins and cytochromes from the
      yellow bioluminescence marine bacterium Vibrio fischeri strain Y1.
AB  - Several flavoproteins and cytochromes that occur as major components in extracts
      of the yellow bioluminescence Y1 strain of the marine bacterium Vibrio fischeri
      have been purified and characterized with respect to their mass (SDS/PAGE and
      matrix-assisted laser-desorption/ionization MS), chromatographic properties, N
      terminal sequence, and spectroscopy (absorption, fluorescence emission and
      anisotropy decay). The investigated proteins were as follows: yellow fluorescence
      protein (YFP) with bound riboflavin, FMN or 6,7-dimethyl-8-ribityllumazine; a
      blue fluorescence protein (BFP) with bound 6,7-dimethyl-8-ribityllumazine,
      riboflavin, or 6-methyl-7-oxo-8-ribityllumazine; thioredoxin reductase with FAD
      as ligand; and two c-type diheme cytochromes, c551 and c554. We present evidence
      that the riboflavin-bound YFP has an N-terminal sequence corresponding to that
      published for the dimeric YFP. We show that an equilibrium replacement of the
      riboflavin can be made with excess lumazine derivative and that lumazine-bound
      YFP has different bioluminescence properties to those of the lumazine protein
      from Photobacterium leiognathi. BFP is a different protein again, and in the
      bacterial lysate it occurs in multiple forms, ligated to either riboflavin,
      lumazine, or the 7-oxolumazine derivative. The N-terminal sequence for BFP shows
      similarities to those of the YFP proteins and to lumazine protein and riboflavin
      synthase from Photobacterium. BFP in any form has no bioluminescence or
      riboflavin-synthase activity. A 70-kDa fluorescent flavoprotein with FAD as
      ligand has an N-terminal sequence highly similar to those of thioredoxin
      reductases from Haemophilus influenzae and Escherichia coli. Cytochrome
      contaminations in previous preparations of YFP have been removed and are
      identified as the two c-type cytochromes c551 and c554. Both inhibit the NADH
      induced bioluminescence in the reductase/luciferase system with the luciferases
      from P. leiognathi and V. fischeri. The N-terminal amino acid sequence of the
      cytochrome (c551) corresponds to a diheme cytochrome c4. The spectral properties
      of c554 are similar to those of other c5 cytochromes, and both c554 and c551 have
      absorption spectra similar to those of the respective cytochromes from the gram
      negative bacteria Pseudomonas and Azotobacter.

PMID- 9183021
TI  - Analysis of the large aqueous pores produced by a Bacillus thuringiensis protein
      insecticide in Manduca sexta midgut-brush-border-membrane vesicles.
AB  - An osmotic swelling assay utilising carboxyfluorescein self-quenching to measure
      intravesicular volume changes was adapted to investigate permeability changes
      induced by the Bacillus thuringiensis Cry1Ac delta-endotoxin in Manduca sexta
      midgut-brush-border-membrane vesicles (BBMV). This assay provides a more
      quantitative analysis of Cry-toxin-induced BBMV permeability changes, extending
      our previously published protocol which employed a light-scattering signal to
      monitor delta-endotoxin activity [Carroll, J. & Ellar, D. J. (1993) Eur. J.
      Biochem. 214, 771-778]. The fluorescence signal changes, supported by electron
      microscopy of the BBMV, demonstrated that Cry1Ac altered the membrane
      permeability for large non-electrolyte solutes. With this approach Cry1Ac was
      observed to induce or form pores freely permeant for raffinose (1.14 nm diameter)
      and using non-electrolytes of increasing size the pores were estimated to have a
      limiting diameter of approximately 2.4-2.6 nm under alkaline pH conditions.

PMID- 9183022
TI  - Electron transfer between spinach plastocyanin mutants and photosystem 1.
AB  - Two distinct regions of plastocyanin, one hydrophobic and one acidic, are
      generally thought to be involved in the electron-transfer reactions with its
      physiological partners, cytochrome f and photosystem 1. To probe the importance
      of the hydrophobic patch in the reaction with photosystem 1, seven mutant
      plastocyanin proteins have been constructed with the following mutations:
      Gly7Ala, Gly8Asp, Ser11Asp, Ser11Gly, Pro36Gly, Ser85Thr and Gln88Asn. The
      electron-transfer reaction was investigated by transient flash-photolysis
      absorption spectroscopy. All proteins remained active in photosystem 1 reduction,
      showing a biphasic reaction. However, the substitution in position 36 resulted in
      a drastic decrease in efficiency, suggesting that this residue is involved in a
      specific contact with photosystem 1. Measurements over a wide range of
      plastocyanin concentration, ionic strength and pH, showed different properties
      for the two kinetic phases. A mechanism involving a rate-limiting conformational
      change accounts well for the observations. Electron transfer from plastocyanin to
      photosystem 1 would thus require a conversion from an inactive to an active
      conformation of the complex. Both hydrophobic and electrostatic interactions are
      important in the dynamics. The structural integrity of a few critical residues,
      including Pro36, is essential for efficient photosystem 1 reduction.

PMID- 9183023
TI  - The absence of the mitochondrial ATP synthase delta subunit promotes a slow
      growth phenotype of rho- yeast cells by a lack of assembly of the catalytic
      sector F1.
AB  - In the yeast Saccharomyces cerevisiae, inactivation of the gene encoding the
      delta subunit of the ATP synthase led to a lack of assembly of the catalytic
      sector. In addition a slow-growth phenotype was observed on fermentable medium.
      This alteration appears in strains lacking intact mitochondrial DNA and showing a
      defect in the assembly of the catalytic sector, such as the yeast strain
      inactivated in the gene encoding the epsilon subunit. In rho mitochondria having
      an intact F1, the ion movement resulting from the exchange of ADP formed in the
      organelle and ATP entering the mitochondrial compartment led to a mitochondrial
      transmembranous potential delta psi that was sensitive to carboxyactractyloside.
      This ion movement was dramatically decreased in rho mitochondria lacking the
      delta subunit and thus the F1 sector, whereas a cell devoid of delta subunit and
      complemented with a plasmid harboring the ATPdelta gene displayed an assembled
      F1, a normal generation time and a fully restored mitochondrial potential. This
      result could be linked to the involvement of the membrane potential delta psi
      which is indispensible for mitochondrial biogenesis.

PMID- 9183025
TI  - Oral mucosal lesions and oral hygiene habits in the home-living elderly.
AB  - A large epidemiological health investigation, the Helsinki Ageing Study (HAS),
      was performed in 1989-1991 in Helsinki, Finland. We report here the prevalence of
      oral mucosal lesions in 338 76-, 81- and 86-year-old home-living elderly people,
      who completed the oral health investigation at the Institute of Dentistry,
      University of Helsinki. One or more lesions were found in 128 subjects (38%).
      Fifty-one per cent of the edentulous complete-denture wearers and 31% of the
      elderly with some natural teeth had mucosal lesions. The most common finding was
      inflammation under the denture, which occurred alone or combined with other
      lesions in 25% of the denture wearers. The three most common mucosal changes not
      related to denture wearing were coated changes of the tongue (7%), angular
      cheilitis (6%) and varicose veins under the tongue (4%). No differences were
      found in the number of mucosal lesions among the three age groups. Angular
      cheilitis and inflammation under removable dentures were more frequent in women
      than in men. However, no other differences were found in the presence of mucosal
      lesions between sexes. The total number of mucosal lesions correlated positively
      with the number of medications used daily. Ninety-six per cent of the subjects
      with complete dentures, and 98% of those with some natural teeth reported
      cleaning their dentures at least once a day. Of the denture wearers, 88% reported
      cleaning their oral mucosa also, as part of their oral hygiene routine. The
      presence of mucosal lesions was related to self-reported cleaning of the denture
      bearing mucosa. However, no association was observed between cleaning frequency
      and presence of mucosal changes.

PMID- 9183024
TI  - Release of cariostatic agents from a new buffering fluoride- and xylitol
      containing lozenge to human whole saliva in vivo.
AB  - A new buffering lozenge (sucking tablet) was developed for patients susceptible
      to dental caries and erosion, in particular for those with reduced salivary
      secretion. As active ingredients this lozenge comprises of a combination of
      xylitol, fluoride, calcium, phosphate, zinc and buffering compounds. To test the
      lozenge's activity in vivo, the release of ingredients was monitored in 19
      healthy subjects for 22 min after sucking the lozenge was completed. In subjects
      with a normal salivary secretion rate the lozenge caused only a slight
      stimulation of saliva flow, but a significant elevation both in salivary pH and
      buffer effect was observed. Furthermore, fluoride, calcium and phosphate were
      effectively released into whole saliva with peak values 2-4 min after use. The
      same salivary parameters were also quantitated after 1 month's regular use (3
      lozenges/day) but no consistent long-term changes were found. Salivary mutans
      streptococci and total anaerobic microflora did not change significantly during
      the long-term use. The results show that the buffering fluoride- and xylitol
      containing lozenge, which also releases calcium and phosphate, is active in vivo
      but its serviceability as a remineralizing agent, in particular for elderly
      patients with reduced salivary flow rate, has to be analysed separately.

PMID- 9183026
TI  - Titanium for removable dentures. I. Laboratory procedures.
AB  - To test the hypothesis that titanium (Ti) removable partial dentures (RPDs) would
      function for a period of at least 2 years without failure, 10 patients were
      selected to receive dentures made from Ti and Co-Cr. The Ti RPDs were constructed
      identically to conventional cobalt-chromium (Co-Cr) dentures. Five complete Ti
      dentures were also included and the laboratory procedures involved for making
      both complete and partial dentures were evaluated. The detection of internal
      defects by radiography made the screening of Ti castings possible and led to a
      rejection of specimens showing porosities of more than 0.5 mm in flexible
      members. Co-Cr frames on the other hand cannot be screened in this way. The
      success rate in the casting of Ti was 60% for both partial and complete dentures,
      but as casting technology has since improved, the rate is expected to be higher,
      particularly where complete denture palates have optimum thickness. The success
      rate in the casting of Co-Cr RPDs was 100% without radiographic screening. The
      weight difference between Ti and Co-Cr RPDs was in the range of 1.3 to 3.9 g at
      issue and is generally higher as the volume of denture frames increases. A large
      difference would be of clinical significance in maxillary complete dentures. The
      low density of Ti allows for the adoption of a useful pre-clinical quality
      control process using commonly available dental X-ray units.

PMID- 9183027
TI  - Reported symptoms from the masticatory system and general well-being in
      rheumatoid arthritis.
AB  - Eighty-one patients with rheumatoid arthritis (RA) and 41 patients with
      temporomandibular disorders (TMD) were evaluated with questionnaires regarding
      subjective symptoms from the masticatory system. The general well-being was
      assessed using the Mood Adjective Check List (MACL) and the Body Symptom Scale
      (BSS). Patients with rheumatoid arthritis in general had less symptoms from the
      masticatory system than TMD patients. The RA patients reported that their
      symptoms were related to acute phases of the general disease, while the TMD
      patients reported that mental stress, anxiety, bruxism and chewing aggravated
      their symptoms. The RA patients had more general physical discomfort than TMD
      patients according to the BSS. The RA patients rated their mental well-being
      (MACL) close to normal, except that they were less active than TMD patients. The
      TMD patients, on the other hand, showed higher values for mental tension. In
      conclusion, many patients with RA will develop TMD symptoms but there is a great
      variation in time relationship between the onset of RA and involvement of the
      masticatory system.

PMID- 9183029
TI  - Effects of surface properties on bond strength between layers of newly cured
      dental composites.
AB  - The shear strength was measured of a polymerizing increment to a newly cured
      composite increment of the same material with various surface properties. The
      results showed that the materials with the original surface which had been cured
      against a cover glass resulted in a significantly higher bond strength than any
      of the other preparations. It was concluded that the unreacted double bonds (due
      to the oxygen inhibition) functioned as a bonding medium between two increments
      of dental composites. The process which impaired the original cured surface
      decreased the bonding between increments.

PMID- 9183028
TI  - Antifungal effect of zeolite-incorporated tissue conditioner against Candida
      albicans growth and/or acid production.
AB  - A new antimicrobial material, Ag-zeolite (Zeomic), was combined with a commercial
      tissue conditioner (GC-Soft Liner (GC); 1-5%) and, through monitoring the pH of
      the growth medium, examined for effects on the in vitro growth and/or acid
      production of Candida albicans on protein-free and saliva-coated specimens. The
      effect of incorporation of this agent on the physical property of the lining
      material was also examined according to the ISO penetration test. Comparison
      studies were carried out using GC, Coe Comfort (CC) or undecylenate combined GC
      (1-5%) specimens. Although the pH changes in the media varied depending upon the
      materials on which the Candida was grown, reverse sigmoidal pH curves were
      observed with most samples. As compared with GC, the soft lining materials
      showed, to some extent, an inhibitory effect on the acid production and/or the
      growth of C. albicans. These inhibitory effects consisted of a delay in the onset
      of rapid pH decline, decreases in the rate of pH change and increases in minimum
      pH. In most cases, the inhibitory effects of test specimens were dose-dependent,
      and zeolite specimens showed a significantly higher antifungal effect, followed
      by CC and undecylenate-combined GC; GC showed the least antifungal effect. The
      inhibitory effects of these materials on fungal growth were decreased by the
      presence of a saliva-coat, particularly with zeolite specimens and CC. However,
      four of eight 5%-Zeomic specimens still exhibited perfect growth inhibition in
      the presence of the salivary pellicle. Furthermore, test specimens containing 2
      5% Zeomic showed a significantly greater effect on the delay in rapid decline of
      pH, as compared with the other specimens examined. In addition, the significantly
      higher minimum pH was observed where the yeasts were grown on 4%- and 5%-Zeomic
      specimens. The physical properties of all the test specimens conformed with the
      ISO standard as examined by penetration test. These results taken together
      suggest that an antimicrobial zeolite-combined tissue conditioner would be a
      potential aid in denture plaque control.

PMID- 9183030
TI  - A three-dimensional non-invasive study of head flexion and extension in young non
      patient subjects.
AB  - Head flexion and extension movements near the natural head position (NHP) were
      analysed for the location of the mean instantaneous centre of rotation (ICR).
      Forty-six healthy young adults (30 women and 16 men) with sound dentitions, free
      from cranio-cervical disorders, performed habitual movements that were
      automatically detected and measured by an infrared three-dimensional motion
      analyser. ICR and curvature radius were calculated for each movement and subject.
      In both extension and flexion, ICR position changed during the motion. The
      movement was symmetrical in all subjects. No gender or flexion/extension
      differences were found for both ICR position and relevant curvature radius. On
      average, ICR relative to NHP soft-tissue nasion was located at about 150% of the
      soft-tissue nasion-right tragus distance, with an angle of about 220 degrees
      relative to the true horizontal. Results suggest that head flexion or extension
      is always performed with a combination of rotation (atlanto-occipital joint) and
      translation (cervical spine) even in the first degrees of motion. Moreover, NHP
      at rest seems to be some degree more flexed and anterior than head position
      during movements. These relative positions and their muscular determinants could
      also influence mandibular posture at rest and during functional movements.

PMID- 9183031
TI  - Silver and fluoride ion release from metal-reinforced glass-ionomer filling
      materials.
AB  - This study was undertaken to examine whether a relationship exists between the
      composition of metal-containing glass-ionomer cements and ion release from these
      materials. Conflicting data on silver release from this type of material has been
      reported and it was felt that further investigation was desirable in view of the
      increasing use of these materials. In this study, the release of ions,
      particularly of silver and fluoride, into deionized water and artificial saliva
      was measured for up to one year. Low levels of silver and copper ions were found
      in both media. The amounts released from alloy-containing materials were
      dependent on the amount of alloy present; lesser amounts were leached from
      cermets. Fluoride ion release was less material-dependent but still lowest for
      cermets. The use of artificial saliva reduced ion release as did increasing the
      maturation time prior to immersion in either liquid.

PMID- 9183032
TI  - Studies of changes in occlusion after the insertion of complete dentures (part
      II).
AB  - The aim of this clinical experimental study was to investigate whether, and what,
      changes in occlusion occur between 3 weeks and 1 year after insertion of complete
      dentures. Twenty-six edentulous patients, who already had their jaw relation
      registered for part I of this study some 357 days before, were re-examined. The
      same special non-arcon measuring articulator was used for determination of any
      positional differences between the presently recorded central condylar position
      with inter-occlusal gap and the equilibrated intercuspal position, from
      approximately 1 year previous. Differences were recorded electronically in the
      condylar area in three dimensions. The position of the condylar balls of the
      measuring articulator in maximum intercuspation had shifted, since the previous
      recording, by about 0.62 +/- 0.04 mm (0.04-1.76 mm) in the sagittal and 0.89 +/-
      0.72 mm (0.01-3.06 mm) in the vertical direction. Whereas the differences
      measured in maximum intercuspation scattered in the sagittal plane uniformly
      around the centric condylar position, in the vertical plane they were shifted
      cranially about an average of 0.77 +/- 0.85 mm (1.06 mm caudally to 3.06 mm
      cranially). The results indicate that in half of the patients from the present
      sample the occlusion did not remain stable, which is assumed to be mainly caused
      by resorption of alveolar bone and abrasion of the acrylic teeth. Therefore, at
      each check-up visit not only the health of the denture-bearing tissues and the
      fit of the dentures, but also the mandibular posture and the occlusion should be
      examined carefully.

PMID- 9183033
TI  - Bonding of titanium with acidic primers and a tri-n-butylborane-initiated luting
      agent.
AB  - Adhesive bonding of titanium was investigated with the use of five primers and
      two luting agents. All of the primers contained acidic methacrylate monomers for
      promotion of metal bonding. Titanium metal specimens were bonded with seven
      combinations of five primers and two luting agents. Durability of the bond was
      evaluated by means of thermocycling. Although all five primers enhanced the bond
      strength to titanium, three of the primers (Super-Bond Liquid, Metal Primer and
      Tokuso Rebase MR. Bond) demonstrated more durable bonds than the other two
      primers (Acryl Bond and All-Bond 2 Primer B). The tri-n-butylborane (TBB)
      initiated luting agent exhibited better bonding ability as compared to
      conventional composite resin. The strongest and the most consistent bond was
      achieved by the combination of 4-methacryloyloxyethyl trimellitate anhydride (4
      META) primer and TBB resin.

PMID- 9183035
TI  - Failure of dental bridges. IV. Effect of supporting periodontal ligament.
AB  - The relationship between bridge failure and the periodontal ligament area of
      their abutments was studied in 156 dental bridges constructed for 132 patients.
      Of the bridges constructed at the College of Dentistry, King Saud University,
      26.9% did not meet the published criteria of Ante's Law while 50.0% of those made
      in general dental practice did not meet the same criteria. However, radiographic
      evaluation of abutment teeth in 56 failed bridges revealed that there were only
      two cases with evidence of overloading the abutments.

PMID- 9183034
TI  - Fibre type grouping in porcine masseter and soleus muscles assessed by the
      enclosed fibre type concept. A statistical and computational analysis.
AB  - Muscle function is determined not only by the frequency of slow (type I) and fast
      (type II) fibres but also the spatial fibre type organization. During ageing as
      well as in muscle disorders, divergencies from the normal pattern may occur and
      are expressed as 'fibre-type grouping'. To elucidate whether intramuscular
      differences in spatial fibre type arrangements may underlie the functional
      heterogeneity of the porcine masseter, the arrangements of intrafascicular type I
      and type II fibres were assessed in terms of the number of enclosed fibres in
      whole fascicles. The intrafascicular proportions of edge- and centrally located
      type I and type II fibres were investigated. Two hundred and forty-two porcine
      masseter fascicles (six masseters) and 63 pig soleus fascicles (five soleus
      muscles) were investigated by ATP-ase histochemistry. All fascicles were from 11
      domestic pigs (1 year, 70-90 kg body weight, all female). Sixty-nine to 90% of
      the total fibres were type II fibres in the porcine masseter (P < 0.01). In four
      of five soleus muscles the type II fibre population was dominant. No enclosed
      type I fibres could be identified in the porcine masseter muscles. This was in
      contrast to the finding of 1270 enclosed type II fibres. Five enclosed type I
      fibres (two soleus) and 361 enclosed type II fibres were identified in the pig
      soleus. The spatial analysis indicated that the fibre type arrangements in the
      porcine masseter muscles were not homogeneous. No biopsies with random type II
      fibre organization were identified. Furthermore, half the number of biopsies
      showed type I fibre segregation. These data suggest that the porcine masseter
      cannot be considered as having one homogeneous structural identity.

PMID- 9183036
TI  - Minimally invasive cardiac surgery, a fleeting fancy or a lasting prospect?

PMID- 9183037
TI  - Changing paradigms in thrombolysis in acute myocardial infarction.
AB  - Acute myocardial infarction occurs when a ruptured coronary artery plaque causes
      sudden thrombotic occlusion of a coronary artery and cessation of coronary artery
      blood flow. This paper reviews the underlying coronary pathology in progressive
      coronary atherosclerosis, mechanisms of plaque rupture and arterial occlusion and
      the time relationship between coronary occlusion and myocardial necrosis.
      Reperfusion can be achieved by chemical thrombolysis with different thrombolytic
      agents. Early lysis is achieved best by prehospital administration, a
      transtelephonic monitor, a mobile intensive care unit, active general
      practitioner treatment or by warning the emergency room of impending arrival of a
      patient. Thrombolytic therapy may be unsuccessful and not achieve Grade III TIMI
      flow in less than 4 h (or even 2 h) due to inadequate or intermittent perfusion
      or reocclusion. Adjuvant therapy includes aspirin and platelet receptor
      antagonists. Bleeding is a constant danger. Direct percutaneous transluminal
      coronary angioplasty (PTCA) may be as effective or better than chemical
      thrombolysis. Reperfusion protects the myocardium and salvages viable tissue. It
      also improves mechanical remodelling of the ventricle. Long-term follow-up has
      shown that quantum leaps of fresh coronary occlusion causes step-wise progression
      in patient disability and that further early, prompt reperfusion can salvage
      myocardium and prevent this inexorable progress of the disease.

PMID- 9183039
TI  - Coronary stenting with AVE microstents in acute myocardial infarction.
AB  - Of 36 patients with acute myocardial infarction (AMI) who were referred for
      direct or rescue coronary angioplasty, 11 (31%) needed stent implantation. In 7
      of them, the stent was implanted because of severe dissection and in 4, because
      of elastic recoil. All patients were discharged without clinical or
      electrocardiographic signs of reocclusion. No death, reinfarction or clinical
      evidence of ischemia occurred during up to 15 months of follow-up.

PMID- 9183038
TI  - Left ventricular filling and ejection fraction after successful percutaneous
      balloon mitral valvuloplasty.
AB  - The effect of percutaneous balloon mitral valvuloplasty (PBMV) on left
      ventricular (LV) filling and ejection fraction (EF) still remains controversial.
      We evaluated LV filling and EF in 23 patients (19 women and four men, mean age
      35.6+/-9.6, range 17-56 years) with mitral stenosis (MS) and sinus rhythm
      immediately before and after successful PBMV not complicated with significant
      mitral regurgitation and arrhythmia during left ventriculography. After PBMV mean
      mitral valve area increased from 1.4+/-0.2 to 2.2+/-0.3 cm2 (P<0.01), mean mitral
      valve gradient (MVG) decreased from 18.6+/-5.7 to 6.9+/-3.2 mmHg (P<0.01) and
      mean left atrial pressure (LAP) decreased from 26.0+/-8.2 to 12.3+/-5.2 mmHg
      (P<0.01). We did not determine any change in EF (before PBMV 61.8+/-9.3% and
      after PBMV 61.8+/-7.6% (P>0.05)). Heart rate did not change significantly before
      and after valvuloplasty (P>0.05). Despite the decrease in LAP and MVG, the early
      diastolic filling fraction of left ventricle did not change (before PBMV 59.5+/
      7.5%, after PBMV 57.8+/-8.9% (P>0.05)). Also, we did not determine any increase
      in LV end diastolic volume index (before PBMV 89.9+/-27.7 cm3/m2 and after PBMV
      84.6+/-20.9 cm3/m2 (P>0.05)). However, LV end diastolic pressure increased
      significantly after PBMV (from 6.6+/-3.0 to 11.3+/-4.9 mmHg (P<0.01)). We
      conclude that in patients with MS, LV diastolic performance is impaired and LV EF
      does not change acutely after PBMV.

PMID- 9183040
TI  - Systolic and diastolic function in patients with chronic heart failure at rest
      and during exercise.
AB  - In our study we tried to evaluate systolic and diastolic function in patients
      with chronic heart failure (CHF) by using some echocardiographic parameters and
      invasively measured pulmonary capillary wedge pressure (PCWP). We studied 19
      patients with CHF NYHA II-III at rest, at the end of isometric exercise
      (handgrip) and during a bicycle stress test. Right heart catheterization and
      echocardiography were simultaneously performed. We measured exchange of blood
      gases, end diastolic volume (EDV), end systolic volume (ESV), ejection fraction
      (EF), peak E velocity, peak A velocity, E/A ratio, deceleration time of E wave
      (DT), time of mitral regurgitation (MR) and effective filling period of left
      ventricle (FP). We divided patients according to the median of PCWP at rest into
      two groups: group A with PCWP< or =11 mmHg (10 pts), group B with PCWP>11 mmHg (9
      pts). In group A mean PCWP at rest was 6+/-2 mmHg, during handgrip 12+/-4 mmHg
      and during bicycle exercise 18+/-6 mmHg. In group B mean values of PCWP were 19+/
      6 mmHg, 26+/-11 mmHg and 33+/-5 mmHg, respectively. All values were significantly
      higher in group B (P<0.01). There was a significant difference in pVO2: in group
      A 18.8+/-3.5 vs. 14.7+/-3.3 ml/kg per min in group B (P<0.03). No differences
      between the groups were noticed in EDV, ESV and EF. The E/A ratio in group A was
      less than 1, in group B greater than 1 with the restrictive pattern. No
      differences between the groups were observed in MR and FP at rest. During bicycle
      exercise, MR was significantly longer (284+/-98 vs. 164+/-79 ms; P<0.05) and FP
      shorter (322+/-99 vs. 421+/-74 ms; P<0.05) in group B than in group A. The
      functional capacity of patients with CHF is influenced not only by EF and other
      systolic variables, but also by filling conditions. The duration of effective
      diastole may be one of the most important of them.

PMID- 9183041
TI  - Effects of enalapril on left ventricular function and exercise performance after
      a first acute myocardial infarction. The EDEN Study Investigators.
AB  - AIMS: To study the effects of early use of enalapril on left ventricular function
      and exercise capacity after a first acute myocardial infarction, 356 patients
      without overt signs of congestive heart failure were randomly allocated to
      receive placebo or enalapril between days 7 and 14 after a first myocardial
      infarction. The study was conducted double-blind in 40 hospitals throughout
      Spain. METHODS AND RESULTS: At baseline and after 26 weeks of follow-up exercise
      stress tests, Doppler-echocardiograms and isotopic ventriculography were
      performed in study participants. At the end of follow-up, patients in the
      enalapril group had lower end-systolic volume compared to those in the placebo
      group (55 vs. 62 ml; P=0.05). No difference in exercise capacity was evident
      between both groups. CONCLUSION: The present study shows that enalapril therapy
      administered between 7 and 14 days after a first acute myocardial infarction
      decreases end-systolic volume and may inhibit the remodeling process of the left
      ventricle.

PMID- 9183042
TI  - A fatal case of Behcet's disease associated with multiple cardiovascular lesions.
AB  - Behcet's disease is recognised as a chronic multisystem disorder with vasculitis
      as its underlying pathological process. Cardiac involvement is rare and often
      associated with poor prognosis. A large right atrial thrombus, pulmonary
      aneurysms and aortic pseudoaneurysm that developed 17 years after surgery for
      bilateral renal artery stenosis is presented in a 26-year-old Behcet's disease
      patient. He was admitted to the hospital with fever of unknown origin associated
      with chest pain, dyspnea, cough, haemoptysis and pulmonary opacity in chest X
      ray. Initial pulmonary CT demonstrated small subpleural infiltrates bilaterally,
      one of which was round and suspected as being metastatic. Examination of open
      lung biopsy demonstrated haemorrhagic infarct surrounded by some occluded
      pulmonary arteries. Subsequent CT showed pulmonary aneurysms compatible with
      Behcet's disease. Echocardiography demonstrated a large pedunculated mass in the
      right atrium. Injection of urographin showed a right atrial mass and a large
      right pulmonary artery aneurysm. The atrial mass was completely excised during
      open heart surgery and was identified as being an organising thrombus. Eight
      weeks later while taking prednisone, he was readmitted because of an infected mid
      sternal wound. CT showed slight separation of the stemum, retrosternal fluid,
      pulmonary arteries aneurysm and ascending aorta aneurysm. The next day, the
      patient died from massive bleeding from his ruptured ascending aortic
      pseudoaneurysm. Bizarre presentation of arterial and venous thromboses or
      arterial aneurysm formation, particularly in young patients, should suggest
      Behcet's disease.

PMID- 9183043
TI  - Autonomic nervous system imbalance and left ventricular systolic dysfunction as
      potential candidates for arrhythmogenesis in Becker muscular dystrophy.
AB  - We evaluated the arrhythmic profile in a population of 20 Becker muscular
      dystrophy (BMD) patients searching for possible correlations between the severity
      of the arrhythmic events, the cardiac autonomic balance (assessed by heart rate
      variability analysis in the time domain) and the degree of left ventricular
      systolic impairment. A population of 14 male healthy individuals served as the
      control group. BMD subjects exhibited lower values of SDNN (P=0.013), SDANN index
      (P=0.008) and 24-h mean heart rate (P=0.002). The total number of premature
      ventricular beats (totPVB) and the number of PVB out of 1000 heartbeats
      (PVB/1000) appeared also higher in BMD subjects (P=0.05 and P=0.046,
      respectively). No difference was found in terms of 24-h mean QTc and 24-h longest
      QT among the two groups. TotPVB and PVB/1000 were inversely related to both the
      ejection fraction (r= -0.620, P=0.004 and r= -0.517, P=0.019) and to the
      shortening fraction (r= -0.568, P=0.009 and r= -0.469, P=0.037). Twenty-four-h
      mean QTc was also inversely related to both the ejection fraction (r= -0.520,
      P=0.019) and the fractional shortening (r= -0.491, P=0.028). These data suggest
      that in BMD there is cardiac autonomic imbalance characterized by sympathetic
      predominance and an increased susceptibility to ventricular arrhythmias, even in
      the absence of overt cardiomyopathy. Furthermore, the severity of the arrhythmic
      profile in BMD appears closely related to the degree of left ventricular systolic
      dysfunction.

PMID- 9183044
TI  - Incidence and clinical significance of short-term recurrent ventricular
      tachyarrhythmias in patients with implantable cardioverter-defibrillator.
AB  - Aims of the present study were (1) to investigate the clinical significance of
      short-term recurrent tachyarrhythmias (STRTs) in ICD recipient, (2) to identify
      basic characteristics of the subgroup of patients with STRTs and (3) to compare
      the frequency and circadian pattern of single arrhythmic events and STRTs. We
      reviewed data from 119 consecutive patients with late generation ICD. All
      registered spontaneous ventricular tachyarrhythmias were divided into STRTs
      (defined as two or more consecutive episodes separated by < or =1 h of sinus
      rhythm) and single events. During a mean follow up of 36+/-18 months (range 2-67
      months) 1849 ventricular arrhythmic events were detected in 57 out of 119 ICD
      recipients (48%). 202 STRTs consisting of 1128 single detection (6+/-7/STRT,
      range 2-52) occurred in 34/57 patients (60%; 6+/-6 per patient, range 1-21).
      Recurrent ventricular tachycardias before device implantation and a high number
      of single arrhythmic events during follow-up distinguished patients with STRTs.
      Cardiac mortality was significantly higher in patients with STRTs (26 vs. 4%,
      P<0.05). The majority of both single episodes and STRTs were registered between 8
      a.m. and noon and in the evening. This study reveals a high incidence of STRTs in
      ICD recipients with spontaneous tachyarrhythmias during follow-up and identifies
      STRTs as prognostic significant events. Comparable circadian variations suggest
      that similar triggering factors may be involved in the genesis of STRTs and
      single tachyarrhythmias.

PMID- 9183045
TI  - Inhalatory pentamidine therapy and the duration of the QT interval in HIV
      infected patients.
AB  - We evaluated the effect of chronic Pneumocystis carinii pneumonia (PCP)
      prophylaxis, with a once a month dose of 300 mg of inhalatory pentamidine
      isethionate, on QT interval duration. We included 22 human immunodeficiency virus
      (HIV)-infected patients: 11 were on this medication and 11 were not. The two
      groups were matched for age, sex and HIV infection stage. No patient had any
      clinical condition or was under any medication known to affect the duration of
      the QT interval. The heart rate-corrected QT (QTc) was obtained by averaging the
      observations of three independent observers. QTc duration was similar in both
      groups. The time separating pentamidine administration and the performance of the
      ECG did not influence the results, neither did the duration of inhalatory
      pentamidine therapy. Our results suggest that inhalatory pentamidine does not
      prolong the QT interval duration and so, as opposed to what has been reported
      concerning intravenous pentamidine therapy, does not seem to induce an increased
      risk of torsades de pointes.

PMID- 9183046
TI  - Factors associated with work resumption: a 5 year follow-up with cardiac
      patients.
AB  - Physiological and psychological parameters of 41 cardiac patients who retired
      after an inpatient rehabilitation treatment in Germany were compared with those
      of 41 patients (matched exactly according to sex, age, and diagnosis) who worked
      after a 5 year follow-up. Both samples were selected from a large pool of 733
      consecutive cardiac patients participating in the rehabilitation program with
      follow-ups at 1, 3 and 5 years. The following physiological parameters were
      assessed: clinical characteristics such as biochemical variables and functional
      parameters of the left ventricle, performance and electrocardiogram during
      ergometric exercise, and medication. Psychological parameters assessed with
      questionnaires comprised: life satisfaction, physical complaints, and illness
      behavior, socioeconomic and anamnestic data. No substantial differences were
      observed for medical data, but psychological parameters showed striking
      differences. Retired patients were characterized by lower work satisfaction,
      complaints of being more handicapped by the disease, higher 'propensity for
      pension', more frequent complaints concerning their general state of health, and
      lower education level.

PMID- 9183047
TI  - Cardiac rehabilitation services in England and Wales: a national survey.
AB  - We sent a short postal questionnaire to 244 centres in England and Wales that
      admitted patients with cardiac conditions. In total, 199 (81%) of the centres
      claimed to provide a cardiac rehabilitation service. Of these, 25 were randomly
      selected as a representative sample and visited in order to obtain detailed
      information concerning the provision of services. Most (18 (72%)) of the centres
      had commenced their rehabilitation programme within the previous 5 years, usually
      at the instigation of interested staff. Patient entry to cardiac rehabilitation
      programmes was restricted; women (who represented only 15% of attenders), elderly
      people (excluded in 10 (40%) centres), and those with more complex problems, such
      as angina or heart failure, were under-represented. The central components of all
      programmes were education and exercise training but there was a wide range in the
      quantity and quality of service provision. Most (22 (88%)) programmes were
      hospital out-patient based, one (4%) was hospital in-patient based, one (4%) was
      community-based and one (4%) was home-based. The staffing and funding of
      programmes was variable, with 7 (28%) having no identified funding. There are
      wide variations in the resources currently available for the rehabilitation of
      patients with coronary heart disease. There is a need for clearer direction of
      these services, in particular to determine minimum service provision. Guidelines
      are necessary to give a framework for this relatively new and rapidly expanding
      service.

PMID- 9183048
TI  - Evaluation of signal-averaged cardiokymography for the detection of ischaemic
      left ventricular dysfunction.
AB  - Cardiokymography (CKG) is a non-invasive method for the detection of patients
      with coronary artery disease (CAD). Issues of the present study were to evaluate
      the feasibility, sensitivity and specificity of a recently developed signal
      averaged CKG system for detecting patients with pharmacologically induced
      ischaemic left ventricular wall motion abnormalities (WMA) during pharmacologic
      stress echocardiography (SE). Precordial CKG curves were recorded in 100
      consecutive patients who underwent dobutamine-SE for suspected CAD. For
      interpretation, CKG curves were classified into three different types, depending
      on the degree of systolic outward motion. CKG test results were regarded as
      positive (indicating myocardial ischaemia) if there was a change of the baseline
      CKG type at peak pharmacologic stress. The CKG test results were positive in 18
      of 27 patients with a pathologic dobutamine-SE (sensitivity 67%), but did not
      show any change of the prior CKG type in 57 of 69 patients with a normal SE
      (specificity 83%). Patients with a true positive CKG test had significantly
      (P<0.05) more echocardiographic segments with WMA than patients with a false
      negative CKG test. CONCLUSIONS: Signal-averaged CKG can detect patients with
      ischaemic ventricular dysfunction. Sensitivity of CKG in detecting patients with
      WMA depends on the extent of left ventricular ischaemia. Further studies are
      needed to define the diagnostic value of signal-averaged CKG in the non-invasive
      detection of patients with suspected CAD.

PMID- 9183049
TI  - Coronary arteriographic and pathological findings in a case of primary
      leiomyosarcoma of the heart.
AB  - A case of primary leiomyosarcoma of the heart diagnosed during life is described.
      Selective coronary arteriography and transoesophageal echocardiography (TOE)
      aided pre-operative differentiation from the more common atrial myxoma.

PMID- 9183050
TI  - Rheumatic mitral and tricuspid valve disease.

PMID- 9183051
TI  - Aortic insufficiency and stenosis in unruptured aneurysm of sinus of Valsalva.

PMID- 9183052
TI  - Evaluation of the respiratory tract after acute exposure to a pyrotechnically
      generated aerosol fire suppressant.
AB  - Fischer 344 rats (250-300 g) were exposed to the resulting aerosols from the
      pyrolysis of Spectrex Fire Extinguishant (SFE) Formulation A, a pyrotechnically
      generated aerosol fire suppressant, at a loading equivalent of 50 or 80 g m(-3)
      air for 15 or 60 min. Exposures were conducted in a 700-1 whole-body inhalation
      chamber under static conditions. The chamber atmosphere was analyzed for mass
      aerosol concentration and size distribution. Clinical observations were taken
      throughout the exposure. Animals were euthanized at 1 h, 6 h, 24 h, 7 days or 14
      days post-exposure and underwent histopathological examination, enzyme analyses
      and wet/dry lung weight determination. No deaths occurred during the study.
      Animals exhibited signs of dyspnea, coughing, lack of coordination and lethargy
      during each exposure. These signs became more pronounced as the load and exposure
      length increased. No lesions were noted in the trachea, lung, heart or abdominal
      organs upon gross examination. A reversible pulmonary edema and olfactory
      necrosis were observed only in those animals exposed to an SFE loading equivalent
      to 80 g m(-3) for 60 min. Protein concentrations increased in the bronchoalveolar
      lavage but no changes in enzyme levels were observed. There was no significant
      difference between the control groups and the exposure groups for wet/dry lung
      weight determination.

PMID- 9183053
TI  - Role of ethanol exposure on cocaine metabolism in rat hepatocytes.
AB  - Cocaine remains a widely abused illicit substance in our society. Cocaine
      hepatotoxicity has been linked to cocaine metabolism. Cocaine can undergo
      hydrolytic inactivation via plasma and hepatic esterases or it can be N-oxidized
      by cytochrome P-450 and FAD-containing monooxygenases. Ethanol is frequently used
      in combination with cocaine. The presence of ethanol can affect the metabolism of
      other agents, depending on the dose and duration of exposure. In this
      investigation, hepatocytes isolated from male Sprague-Dawley rats were utilized
      to study the effect of ethanol exposure on cocaine metabolism. Hepatocytes were
      isolated using a two-step collagenase perfusion system. Hepatocytes (2 x 10(6)
      cells ml(-1)) were exposed to cocaine, ethanol or the combination of cocaine and
      ethanol for a 2-h period in a shaking water-bath at 30 oscillations per minute
      maintained at 37 degrees C. Sodium fluoride (NaF) was added to aliquots of cells
      which were removed from the incubation following 30, 60 and 120 min. The cells
      were homogenized on ice and immediately extracted for the quantification of
      cocaine, benzoylecognine, norcocaine and ethylcocaine by HPLC. Quantitative
      analysis revealed that there was a time-dependent increase in the disappearance
      of cocaine from hepatocytes. The rate of cocaine disappearance was not changed
      when ethanol was included in incubations containing cocaine. However, in the
      presence of ethanol there was a difference in the quantities of cocaine
      metabolites produced. When ethanol was included in incubations containing
      cocaine, the formation of norcocaine and benzoylecognine was less than that
      formed in hepatocytes exposed to cocaine alone. Additionally, when hepatocytes
      were exposed to cocaine in combination with ethanol, the formation of
      ethylcocaine was linear with time. This study revealed that in the presence of
      ethanol, cocaine qualitative metabolism is altered.

PMID- 9183054
TI  - Evaluation of the dermal carcinogenic potential of re-refined base stocks using
      the modified Ames assay, PAC analysis and the 32P-postlabeling assay for DNA
      adduct induction.
AB  - The standard method for assessing the carcinogenicity of lubricating oil base
      stocks is the mouse skin-painting bioassay. This assay has the advantage of
      directly measuring the endpoint of interest, dermal carcinogenicity, but has the
      drawback of being time-consuming and expensive. For this reason, a variety of
      biological and chemical assays have been developed as predictive alternatives to
      the in vivo assay. This publication describes the application of three such
      methods to the assessment of carcinogenic potential of hydrotreated, re-refined
      oils: the modified Ames test, the analytical determination of 3-7-ring polycyclic
      aromatic compound content and the 32P-postlabeling assay for DNA adduct
      induction.

PMID- 9183056
TI  - Dual role of testosterone in fenvalerate-treated mice with respect to thyroid
      function and lipid peroxidation.
AB  - Effects of testosterone propionate (TP, 2.5 mg kg(-1) body weight) in fenvalerate
      induced (120 mg kg(-1) body weight) thyroid dysfunction and lipid peroxidation
      were investigated in male mice. Testosterone propionate aggravated in the
      inhibition of hepatic type I iodothyronine 5'-monodeiodinase (5'D-I) activity,
      coupled with a decrease in serum triiodothyronine (T3) concentration in pesticide
      treated mice. However, it could ameliorate the toxicity as indicated by decreased
      hepatic lipid peroxidation (LPO) with a marginal but significant increase in
      superoxide dismutase and catalase activities following fenvalerate treatment.
      While protective effects of testosterone on LPO indicated its antiperoxidative
      property, the decrease in 5'D-I activity could be because of the increased
      accumulation of fenvalerate in the tissues following TP administration.

PMID- 9183055
TI  - Screening toxic effects of volatile organic compounds using Drosophila
      melanogaster.
AB  - The suitability of Drosophila melanogaster for biological screening of the toxic
      effects of volatile organic compounds was investigated. Adult flies were exposed
      to vapours of some organic solvents and gasoline under saturating conditions in
      the sublethal range. In some cases the dose-response relationship was studied. As
      a measure of the overall metabolism, CO2 production was recorded before and after
      exposure, including the recovery period, and the body activity was scored and
      classified as "normal behaviour", hyperactivity or excitement or narcosis.
      Significant differences were observed for the different solvents and volatile
      mixtures (vapours of acetone, benzene, methanol, toluene, xylene, diethylether,
      leaded and unleaded gasoline and diesel fuel). The length of the narcosis induced
      by the volatile organic compounds correlated well with their octanol-water
      coefficients. After exposure to benzene, toluene and gasoline a marked increase
      in the CO2 production during narcosis was observed. Methanol exposure led to a
      long-lasting increase in CO2 production, but did not cause narcosis. There were
      also differences in the behaviour (body activities) in the recovery phase between
      the solvents tested. Thus, the results from these experiments suggest that the
      measurement of CO2 production combined with the scoring of body activities in
      Drosophila can be used as a sensitive screening procedure in inhalation
      toxicology, revealing different types of toxic reactions for different types of
      volatile compounds.

PMID- 9183057
TI  - Reactions of tannins with human serum proteoglycans.
AB  - Incubation of an isolated human serum proteoglycan fraction with a tannic acid or
      oak tannin fraction caused a dose-dependent decrease in the total glycan content
      and a special diminution of a major proteoglycan band with molecular weight 112
      kDa in samples as analyzed by polyacrylamide electrophoresis and with
      carbohydrate staining. Tannic acid was more active than oak tannins while the
      spruce tannin fraction caused almost no effects. The concentration of plant
      tannin extracts is often expressed as tannic acid equivalents, which may
      overestimate their biological activity in this model. This cell-free model may
      act as a versatile tool for studies on macromolemular interactions of plant
      polyphenols.

PMID- 9183058
TI  - In vitro and in vivo assessment of the pulmonary toxicity of cellulose.
AB  - The lung-damaging effect of intratracheally administered cellulose was studied by
      biochemical and histological methods. Cell count, protein, phospholipid, lactate
      dehydrogenase and acid phosphatase were determined in bronchoalveolar lavage
      fluid 1, 3 and 7 days after intratracheal instillation. Histological tests were
      performed after days 1, 3 and 30. In vitro, cellulose did not damage the
      macrophage cells. In vivo, interstitial oedema as well as the initial signs of
      inflammation could be detected in the lung after the first day. Inflammation
      after 1 week could be noted, partly interstitial and partly intra-alveolar and
      intrabronchial. In the bronchoalveolar lavage fluid, protein, lactate
      dehydrogenase, acid phosphatase, phospholipid and cell count were enhanced after
      days 1 and 3. After 1 month, the developing bronchioalveolitis is fibrous in
      character. Contrary to the in vivo study, cellulose did not damage rat peritoneal
      macrophages.

PMID- 9183059
TI  - Surveillance of hospital acquired infections needs change to be effective.

PMID- 9183060
TI  - Effects of dietary oil contamination and absence of prophylaxis on orthodontic
      bonding.
AB  - The effect of contamination by dietary oil on acid etching has not been reported
      in the literature. If dietary oil adversely affects acid etching, then a decrease
      in bond strength is expected. This in vitro study investigated the bond strength
      of brackets bonded to tooth surfaces that had been contaminated with dietary oil
      and on which prophylaxis was not carried out. The mean shear bond strengths for
      the control, teeth with oil contamination and teeth with oil contamination but no
      prophylaxis undertaken were 53.33 +/- 14.31 (SD), 61.76 +/- 19.32 and 64.12 +/-
      17.90 N, respectively. An analysis of variance (ANOVA) test showed that there was
      no significant difference between the three groups. The power of the ANOVA was
      calculated for the minimum clinical change that would be worth detecting and was
      found to be approximately 1.0. It can therefore be concluded that the presence of
      dietary oil on the tooth surface does not adversely affect shear bond strength,
      even if prophylaxis is not carried out. Bond failures for all three groups
      occurred mainly at the tooth-adhesive interface.

PMID- 9183061
TI  - The drum spring (DS) retractor: constant and continuous force for canine
      retraction.
AB  - Although much research has been undertaken on the rate of tooth movement, with
      different hypotheses having been put forward, the concepts of the threshold,
      light, heavy and optimal forces are not still clear. It has been stressed that an
      ideal orthodontic spring should have the ability to release a constant force
      throughout the entire range of its activation, but using traditional techniques
      applied initial force will decrease, depending on its deactivation due to the
      tooth movement and the physical properties of the force delivery system. The
      purpose of this study was to test the clinical use of a new and original spring,
      the drum spring (DS) retractor (developed in 1992), which applies a constant and
      continuous force without the need for reactivation, and to compare the effect of
      a constant and continuous force versus a continuous but diminishing force
      produced by a traditional pull coil (PC) retractor system on the rate of upper
      canine retraction. The clinical sample consisted of 15 patients with upper first
      premolar extractions. For each patient, the upper right canine was retracted by
      using a DS retractor applying a constant and continuous force of 50 g; the upper
      left canine was fitted with a conventional PC applying an initial force of 50 g,
      diminishing proportionally with the distal movement of the canine. In addition,
      each group was divided according to the age of each patient: eight patients
      (three males, five females) between 11.8 and 14.4 years of age (mean 13 +/- 1.2
      years) represented the adolescent group, and seven patients (three males, four
      females) between 18.8 and 21.6 years of age (mean 18.2 +/- 1.9 years)
      representing the adult group. The experimental period started 1 week after the
      extraction of the first premolars. During this period no archwire was used, to
      avoid friction and force level changes, and the both springs were attached to a 6
      mm hook fixed on the canine bracket to reduce tipping. The PC retractor was
      reactivated every 3 weeks whereas the DS retractor was left untouched over the
      entire experimental period. The study was continued until one of the two canines
      was completely retracted. The DS retractor was successful for space closure
      without any reactivation, and the continuous and constant force provided a more
      rapid canine movement than the continuous but diminishing force. Canine
      retraction occurred faster in adolescents than in adults. An entire field of
      clinical and research applications may be influenced by this new type of spring.

PMID- 9183062
TI  - Differential growth and maturation in idiopathic growth-hormone-deficient
      children.
AB  - This study describes and compares the growth and maturation of idiopathic growth
      hormone deficiency (IGHD) and evaluates the potential effects of growth hormone
      therapy. The sample includes 40 idiopathic growth-hormone-deficient children
      grouped according to duration of growth hormone replacement therapy. Somatic and
      craniofacial development, skeletal maturation and dental maturation were
      evaluated and compared. The results showed consistent delays in the maturity
      indices for IGHD children. Height age displayed the greatest delay (3 years)
      followed by skeletal age (2.2 years) and dental age (0.8 years). Overall
      craniofacial growth deficiencies were also demonstrated. Anterior cranial base
      and mandibular length were most affected; posterior cranial base length and
      facial heights were least affected. Analysis of covariance, controlling for the
      starting age of therapy, showed significant differences between children grouped
      according to duration of growth hormone therapy. Catch-up growth with hormonal
      therapy was established for height, facial height, skeletal age and posterior
      cranial base length. It was concluded that the various craniofacial skeletal
      components have different potentials for growth retardation with IGHD; catch-up
      growth following growth hormone replacement therapy was greatest for the
      components with the greatest initial (or baseline) growth potential.

PMID- 9183063
TI  - Catch-up growth induced by growth hormone in the craniofacial skeleton of the
      Snell strain of the hypopituitary dwarf mouse.
AB  - Immature Snell strain dwarf mice were treated with human growth hormone for 20
      and 40 days, between the ages of 22 and 41 days and 22 and 61 days, respectively.
      Mature dwarfs were similarly treated for 20 and 40 days between the ages of 62
      and 81 days and 62 and 101 days, respectively. These groups of treated mice were
      compared with untreated dwarfs and normal mice reared under the same conditions.
      The catch-up growth effected by human growth hormone on the craniofacial and
      somatic development of the Snell strain dwarf mouse at both immature and mature
      ages was considerable, overall being approximately 14 per cent. Neurocranial
      parameters tended toward the values of normal mice achieving 89-98 per cent of
      normal growth. Viscerocranial parameters showed greater catch-up, from a lower
      start point, reaching 81-93 per cent of the control. This catch-up in mature mice
      (aged 82-102 days) was at a time when any substantial growth in either dwarf or
      normal mice has usually ceased.

PMID- 9183065
TI  - Mandibular growth pattern in Turner's syndrome.
AB  - In a group of 15 women with 45,X chromosome constitution, mandibular growth type
      was investigated by using both linear and angular measurements. The sum of the
      saddle, articular and gonial angle, lower gonial angle and y-axis was
      significantly greater. In addition the posterior-anterior facial height ratio in
      women with Turner's syndrome was significantly smaller than in the controls (61
      women with 46,XX chromosome constitution), indicating a tendency to backward and
      downward growth changes in the mandible, caused by an X chromosome deficiency.

PMID- 9183064
TI  - Long-term dental development in children after treatment for malignant disease.
AB  - A radiographic dental examination was performed in 16 children conditioned with
      total body irradiation (TBI) and cyclophosphamide (CY) prior to bone marrow
      transplantation (BMT), and in 52 children treated with multiagent chemotherapy.
      For each child, three age- and sex-matched healthy controls were selected.
      Evaluation of disturbances in dental development and tooth size was based on
      planimetric measurements of mandibular teeth on panoramic radiographs. Short V
      shaped roots were diagnosed in 94 per cent of the children treated with TBI/CY
      compared with 19 per cent in the chemotherapy group (P < 0.001). Children
      receiving TBI/CY also exhibited a pronounced reduction in tooth size compared
      with the controls. Reductions varied from 19 per cent in incisors to 39 per cent
      in the second molars. In the chemotherapy group the corresponding values were 7
      and 15 per cent respectively. When comparing crown/root ratios, the indices for
      incisors, canines (P < 0.05) and molars (P < 0.01) in the BMT group were
      significantly higher than the corresponding values in the control group. This
      indicates that the reduction in root size was more pronounced than the reduction
      in crown size. The premolars in the BMT group exhibited a similar reduction in
      crown and root size. All developing teeth were affected by multiagent
      chemotherapy and radiation therapy. The most severe disturbances were found in
      children treated with TBI/CY at a young age.

PMID- 9183066
TI  - Study models of 5 year old children as predictors of surgical outcome in
      unilateral cleft lip and palate.
AB  - This study examined features of dental occlusion in patients born with a
      unilateral cleft lip and palate (UCLP). The intention was to develop a 'Goslon
      type' index for 5 year old children. The Goslon ranking system was used on
      longitudinal study models taken at 5 and 10 years of age of the same patients.
      All patients had UCLP and this had been repaired using a Millard type lip repair
      and a Veau Wardill or Von Langenbeck palatal closure. There was good intra
      examiner agreement for ascribing 5 and 10 year old models to one of five
      categories (excellent-very poor). Inter-examiner agreement on both sets of models
      was at worst moderate. Two of the examiners identified up to 93 per cent of 5
      year old models which either remained in the same category or deteriorated by 10
      years of age. At worse the results demonstrated 70 per cent of cases of 5 years
      of age remained in the same category or deteriorated by 10 years of age.
      Consensus agreement has produced five categories of outcome for these 5 year old
      models. This new index is to be subjected to further validation. This study has
      therefore provided, for the first time, a mechanism for assessing the results of
      CLP surgery earlier than indices already available.

PMID- 9183067
TI  - Normal eruption of the maxillary canine quantified in three dimensions.
AB  - The normal eruption path of maxillary canine teeth was quantified on annual
      lateral and depressed postero-anterior cephalometric radiographs of 15 females
      and 15 males aged 5-15 years. The lateral view was rotated so that the horizontal
      coincided with the Frankfort plane on the depressed views, thus orientating the
      two views in space. Successive positions of canine cusps were marked on tracings
      of both views superimposed on the anterior outline of the zygomatic process. All
      positions of the canine cusps were digitized and the horizontal, vertical and
      lateral annual differences found by subtraction, taking the first position of the
      canine as the origin. The chronological data were corrected for enlargement and
      adjusted to increments of 12 months. Adjustments were also made to take into
      account varying ages of eruption. Posterior movement occurred between 7 and 13
      years (all three years before eruption, the year of eruption and the following
      year). Vertical movement occurred between 5 and 13 years (all of the six years
      before eruption, the year of eruption and the following year). Lateral movement
      tended to be in a palatal direction up to 2 years before eruption followed by
      significant buccal movement in the year before eruption, the year of eruption and
      the following year. Data are given for eruption in three planes.

PMID- 9183068
TI  - Long-term effects of Class II correction in Herbst and Bass therapy.
AB  - This study compared the initial and long-term skeletal and dental effects of
      Herbst and Bass appliance therapy for correction of Class II malocclusion. The
      sample comprised 18 pairs of boys matched for growth period at the time of
      therapy, with similar pre-treatment sagittal and vertical jaw base relationships.
      One boy in each pair was treated with the Herbst and the other with the Bass
      appliance. At follow-up, 15 boys of the Herbst group and 17 of the Bass group
      were available. Lateral cephalograms in centric occlusion taken before treatment,
      after 6 months of treatment and at the end of growth were analysed. After 6
      months of treatment the Bass appliance seemed to have a greater effect on
      mandibular jaw base position. The correction of overjet and sagittal molar
      relationship was more complete in the Herbst patients due to dental changes. At
      follow-up varying effects both between and within pairs were observed. Overall,
      the skeletal and dental changes from start of treatment to end of growth were of
      the same magnitude. A restraining effect on the position of the maxilla was
      observed in both groups, somewhat more pronounced in the Bass sample. Both
      treatment methods are most useful in correction of severe Class II malocclusions.
      It was, however, difficult to find possible differences in treatment effects
      between the two methods due to great individual variations of growth.

PMID- 9183069
TI  - A comparative study of sagittal correction with the Herbst appliance in two
      different ethnic groups.
AB  - The dentofacial morphology of Chinese is different from Caucasians. The purpose
      of this investigation was to assess the skeletal and dental changes contributing
      to the sagittal correction in group of consecutive Chinese children who were
      treated with the Herbst appliance. A comparison was made between 14 Chinese and
      14 Swedish subjects who all had Herbst appliance treatment. All subjects were
      corrected from the Class II division 1 malocclusion to an overcorrected Class I
      or Class III dental relationship within a 6-8 month period. Lateral cephalograms
      taken before and immediately after the Herbst treatment were analysed. In
      general, the skeletal and dental changes during treatment were comparable between
      both ethnic groups. However, individual variations within the two groups were
      wide. It can be concluded that the Herbst appliance was equally successful in
      Southern Chinese children and similar treatment changes as those achieved in
      Swedish children could be found.

PMID- 9183070
TI  - Effects of experimental unilateral condylectomy followed by altered mandibular
      function on the maxilla and zygoma.
AB  - The effect of protruded mandibular function on the maxilla and zygoma was studied
      in young unilaterally condylectomized growing rats. Forty-eight-4-week-old rats
      were divided into two experimental and two control groups as follows: group A, 12
      animals unilaterally condylectomized on the right side; the mandible was allowed
      to function normally; group B, 12 animals unilaterally condylectomized on the
      right side; the mandible was protracted forwards immediately by means of an
      appliance; group C, 12 animals sham-operated on the right side; no condylectomy
      or mandibular protraction; and group d, 12 control animals not subjected to any
      operation or mandibular protraction. The mandibular protraction was achieved by
      an appliance consisting of an acrylic collar brace fitted to the animal's neck
      and supporting rubber bands pulling on an intraoral part cemented on the animal's
      lower incisors. Twenty-five grams of pulling force and protrusion to a clinically
      and radiographically testes anterior crossbite was exercised for 12 hours per
      day. The experimental period was 30 days. Lateral and dorsoventral radiographs
      were taken on days 1 and 30 following condylectomies and mandibular protraction.
      Cephalometric analysis was performed for each animal with measurements evaluating
      the maxilla and zygoma. Statistical analysis and comparison of the findings in
      the four groups of animals can be summarized as follows: (i) condylectomy and
      altered mandibular function may produce remote skeletal reactions in other parts
      of the cranial complex; and (ii) the ipsilateral maxilla is affected by
      condylectomy of the mandible, but altered mandibular function by protraction
      compensates for the results of condylectomy.

PMID- 9183071
TI  - Altered mandibular function and prevention of skeletal asymmetries after
      unilateral condylectomy in rats.
AB  - Unilateral condylar injury is known to be a frequent cause of mandibular
      asymmetry. Whether this is due to the trauma itself or to the disturbed function
      that follows the injury is a very important question with ramifications for
      clinical complications related to facial asymmetries. The aim of this study was
      to test the hypothesis that mandibular function in a protruded position can
      compensate for the absence of one condyle and prevent potential growth
      asymmetries. Forty-eight 4-week-old rats were divided into two experimental and
      two control groups consisting of 12 animals each, as follows: (A) unilateral
      condylectomy was performed on the right side and the mandible was left to
      function normally; (B) after unilateral condylectomy on the right side, the
      mandible was forced to function in a protruded position; (C) a sham operation was
      performed in the condylar area of the right side but no appliance was used; and
      (D) 12 animals were used as controls without any operation or appliance.
      Mandibular protraction was achieved by means of a specific appliance, acting via
      rubber bands, pulling the mandible in a straight, forward direction with a force
      of 25 g for 12 hours per day. The experimental period was 30 days. Dorsoventral
      radiographs were taken and vital dyes were administered at three time intervals,
      i.e. on days 1, 15 and 30, for all animals. Cephalometric analysis included 14
      measurements. Findings resulting from statistical analysis and comparisons of
      measurements obtained in the four groups can be summarized as follows: (i) when
      comparing group A with groups C and D, less growth was found in the right
      mandibular sides in group A; (ii) when comparing group B and groups C and D, less
      growth was found in the right mandibular sides in group B; (iii) when comparing
      groups A and B, more growth was found in the right mandibular sides in group B;
      (iv) when comparing the right and left mandibular sides in group A, less growth
      was found in the right side; and (v) when comparing the right and left mandibular
      sides in group B, no significant growth differences were found. These findings
      support the hypothesis that altered mandibular function in a protruded position
      can compensate for the effects of unilateral condylectomy and prevent the
      appearance of skeletal mandibular asymmetries in growing rats.

PMID- 9183072
TI  - A post-treatment evaluation of multibonded ceramic brackets in orthodontics.
AB  - The purpose of this study was to perform a clinical evaluation of ceramic
      brackets with silane-coated bases for chemical (Transcend) and microcrystalline
      bases for mechanical (Transcend 2000) retention. The sample consisted of 49
      consecutive patients; the first 30 were treated with brackets with chemical
      retention and the following 19 with brackets with mechanical retention. For each
      patient the brackets on one side of the mouth were assigned at random to be
      bonded with Concise and the other with Transbond as recommended by the
      manufacturers. Levelling and alignment of severely displaced roots was initiated
      with superelastic wires and completed with stainless steel wires. Any space
      closure or correction of interarch discrepancy was performed with rectangular
      stainless steel wires. The brackets with chemical retention were removed with a
      torsional rotation debonding wrench, and those with mechanical retention with a
      tensile debonding plier. The bond failure rate was low, with no difference
      between the two bracket types or between brackets bonded with Concise and
      Transbond. Bracket fracture was a significant clinical problem, both during
      active treatment and at the time of appliance removal. New teeth with formation
      of pronounced enamel cracks were seen in 20.6 and 10.5 per cent of the teeth
      treated with brackets with chemical and mechanical retention, respectively (P <
      0.001), with no difference between teeth bonded with Concise and Transbond.
      Enamel tear-outs were seen in 3 of the 544 and in 1 of the 344 teeth treated with
      the respective types of bracket. These teeth were bonded with Concise.

PMID- 9183073
TI  - Epidemiological features of acquired immunodeficiency syndrome in southern India.
AB  - AIDS was diagnosed in 187 men and 24 women (M:F = 8:1) from April 1987 till
      December 1994 at the Christian Medical College Hospital, Vellore. The doubling
      time of the occurrence of AIDS cases was 14 months; during 1987-90 there were an
      average of 5.7 cases per year; in 1991-93 there were 28 per year; in 1994 there
      were 104 cases. The mean age of patients was 33 yr for men and 31 for women.
      Among men, the primary mode of infection was heterosexual contact with female
      commercial sex workers. Among women, the most common source of infection was
      their husbands. There were 4 bisexuals and one homosexual subject who might have
      acquired infection by having sex with other men. There were 135 subjects from
      urban and 76 from rural communities. Most subjects belonged to the lower socio
      economic classes. These data show that HIV infection had been very widespread in
      this region, both urban and rural.

PMID- 9183074
TI  - High level aminoglycoside resistance in enterococci isolated from hospitalized
      patients.
AB  - Drug resistance in enterococci isolated from hospitalized patients is reported.
      Out of 421 strains tested, 45 (10.7%) showed high level aminoglycoside resistance
      (HLAR). At the species level, 8.2 per cent of Enterococcus faecalis and 33.3 per
      cent of E. faecium were HLAR. While all the strains of E. faecalis were sensitive
      to vancomycin, one strain of E. faecium was vancomycin resistant.

PMID- 9183075
TI  - Comparative evaluation of two indigenously developed tests for rapid detection of
      group-A streptococci directly from throat swabs.
AB  - The efficacy of two indigenously developed rapid tests, latex agglutination and
      antibody capture assay (a colour immunochromatographic assay) to detect group A
      Streptococcus pyogenes (GAS) was evaluated in comparison with the traditional
      culture method ('Gold Standard') in both asymptomatic children (1500) and
      symptomatic patients (233). Throat swabs were taken in duplicate and rapid tests
      performed on one swab and culture on the other. Both latex agglutination and
      antibody capture assays showed a sensitivity of 100 per cent and specificity of >
      98 per cent as compared to culture and isolation in symptomatic patients.
      However, among asymptomatic carriers sensitivity of 100 per cent and 87.5 per
      cent and specificity > 95 per cent were observed for latex agglutination and
      antibody capture assays respectively. Latex agglutination showed no false
      negative results and sensitivity was not affected by low beta-haemolytic counts
      in asymptomatic children. The rapid tests described here will help in the
      detection and thereby the management of GAS infection.

PMID- 9183076
TI  - Dynamics of malaria transmission near two permanent breeding sites in Baringo
      district, Kenya.
AB  - Entomological and malario-metric measurements were made near two permanent
      breeding sites in Baringo district, Kenya in order to determine the prevalence
      and seasonality of malaria and the relative importance of two local anopheline
      mosquitoes as malaria vectors. The breeding sites studied were the Perkerra
      irrigation scheme and the Loboi swamp, whereas the mosquito species involved were
      Anopheles gambiae Giles (sensu lato) and Anopheles funestus Giles. Malaria
      accounted for 54 per cent of annual clinic attendance in the district and
      transmission occurred throughout the year. Overall values of vector density, man
      biting rate and crude inoculation rates did not differ significantly between the
      two areas. However, there was a strong seasonal trend in the values of these
      parameters which varied between the two sites, resulting in peak transmission
      occurring at different times of the year, April-July in Lobio and August-October
      in Perkerra. Crude inoculation rates were about 5 times higher in An. gambiae
      than in An. funestus, indicating that the former was the more efficient and more
      important vector in the district.

PMID- 9183077
TI  - Measurement of total energy expenditure by the doubly labelled water technique in
      free living Indians in Bangalore city.
AB  - Doubly labelled (2H2(18)O) water was used to determine the daily total energy
      expenditure (TEE) in the free living state of 6 adult, healthy, weight stable,
      male volunteers over a period of 21 days. The body weights of the subjects ranged
      from 42.3-70.4 kg. Isotope pool sizes and elimination rates were calculated from
      18O and 2H enrichments in basal and daily (21 days) post dose urine samples using
      the multipoint slope intercept method after corrections for isotope
      fractionation. The physical activity level (PAL) of the subjects was also
      measured during the experiment as the ratio of measured TEE to measured basal
      metabolic rate (BMR). Simultaneous prediction of the total energy expenditure was
      also carried out by combining the measurements of BMR by indirect calorimetry,
      and daily physical activity level by 7 day recall. TEE calculated by the isotopic
      technique was 9.35 +/- 2.00 MJ/day, with an inter individual variation of 21.4
      per cent. The measured BMRs in the subjects along with PALs obtained by recall,
      gave a total daily energy expenditure of 8.66 +/- 2.20 MJ/day with an inter
      individual variation of 25.4 per cent. The average BMR was 5.59 +/- 0.99 MJ/day
      and the average PAL (by recall) was 1.54 +/- 0.12. The inter individual variation
      of the BMR was 17.7 per cent and that of the recalled PAL was 7.9 per cent; the
      latter increased to 12.2 per cent when the PAL was calculated from the ratio of
      the measured TEE to the BMR. There was no significant differences between the
      methods (isotopic and predicted by BMR), although, the TEE obtained by the
      isotopic method was higher, by about 0.7 MJ/day, or 7.9 per cent, than the TEE
      predicted by BMR.

PMID- 9183078
TI  - Colonic function in cirrhosis of liver & in healthy controls.
AB  - Total and segmental colonic transit time (radio-opaque marker method), daily
      stool weight, stool water and stool frequency were estimated in 10 decompensated
      nonalcoholic male cirrhotics and 10 male controls. Total and left colonic transit
      times were significantly shorter (P < 0.05) in cirrhotics as compared to
      controls. Stool frequency was significantly higher in cirrhosis (P < 0.01) and
      showed a significantly negative correlation (r = 0.73, P < 0.02) with total
      colonic transit time. Stool wet weight and water content were significantly
      higher in cirrhosis (P < 0.01) as compared to controls. Colonic transit was
      accelerated in cirrhosis and may be an important hitherto unrecognised factor in
      the etiopathogenesis of diarrhoea observed in patients with cirrhosis.

PMID- 9183079
TI  - Human heat tolerance in simulated environment.
AB  - The heat tolerance of 11 male volunteers were examined under seven climatic
      conditions in a climatic chamber. The conditions were 38 to 49 degrees C dry bulb
      temperature and 45 to 80 per cent relative humidity, i.e., 32.3 to 40 degrees C
      effective temperature-basic [ET(B)]. The ET(B) values were equated to other heat
      stress indices, e.g., WBGT (Wet-bulb Globe Temperature Index) and Oxford Index.
      The subjects did ergometric work at an intensity of 60 per cent VO2max. The
      exposure durations were decided by the cardiorespiratory, body temperature and
      sweating responses. Of the climatic conditions studied, at 35.4, 38, 39 and 40
      degrees C ET(B), the body core temperature (Tcr) reached over 39 degrees C and
      heart rates attained 172 to 182 beats/min, which were taken as the tolerance
      limit. The total oxygen demand significantly varied with the increase in
      environmental warmth, i.e., increase or decrease of one litre of oxygen demand
      was equivalent to one minute change in tolerance time. The volunteers were not
      susceptible to heat; only in extreme hot situations beyond 35.4 degrees C ET(B),
      were unacceptable levels of physiological and psychophysical reactions seen. The
      study suggests the acceptable and tolerable limits for human exposure in heat:
      (i) acceptable at 38 to 38.2 degrees C Tcr for a tolerance time of 80 to 85 min;
      and (ii) the tolerable limit of short duration (40-45 min) at 39 degrees C Tcr
      that corresponded to 31.5 and 36.5 degrees C ET(B).

PMID- 9183080
TI  - MIB-1 proliferative index in parathyroid adenoma & hyperplasia.
AB  - A retrospective study on 22 cases of parathyroid adenoma, 9 cases of primary
      parathyroid hyperplasia and 14 specimens of normal suppressed glandular tissue
      was undertaken to determine the usefulness of proliferative index (PI) for
      discriminating adenoma from hyperplasia, as an adjunct to the existing
      histological criteria. PI was determined by avidin-biotin-complex immunostaining
      after high temperature microwave antigen retrieval in paraffin sections, using
      monoclonal MIB-1 antibody which detects paraffin resistant analogue of cell cycle
      associated Ki-67 antigen. PI expressed as percentage positive cell nuclei, was
      1.36 +/- 0.62 (range 0.04-2.72) in adenoma, 1.17 +/- 0.83 (0.02-1.98) in
      hyperplasia and 0.03 +/- 0.02 (0.00-0.06) in normal suppressed glandular tissue.
      While the difference between normal suppressed glandular tissue and adenoma and
      hyperplasia was significant (P < 0.001), that between adenoma and hyperplasia was
      not. We conclude that although PI could distinguish between normal suppressed
      glandular tissue versus glands with primary hyperparathyroidism, it failed as an
      additional useful parameter for discriminating between adenoma and hyperplasia,
      both of which have low but similar proliferative activity.

PMID- 9183081
TI  - Pharmacologic characterization of muscarine receptor subtypes in rat gastric
      fundus mediating contractile responses.
AB  - The role of four muscarinic receptor subtypes M1, M2, M3 and M4 which have been
      characterized pharmacologically was examined in motility control of isolated rat
      gastric fundus. Acetylcholine produced concentration-dependent tonic contraction
      of isolated rat fundus (EC50 = 9.64 +/- 0.14 x 10(-8)M). These contractions were
      concentration-dependently antagonized by atropine (KB = 2.45 x 10(-11)M), M1
      selective blockers telenzepine (KB = 6.64 x 10(-11)M) and pirenzepine (KB = 2.3 x
      10(-8)M), and hexocyclium (KB = 2.82 x 10(-10)M). M3-selective blocker p-fluoro
      hexahydro-sila-difenidol (pFHHSiD) was a less potent antagonist (KB = 2.3 x 10(
      8)M), while M2 and M4-selective methoctramine produced only weak blockade of
      tonic contractions caused by acetylcholine (KB = 4.68 x 10(-6)M). These results
      suggest that only M1 and M3 muscarinic receptors have functional roles in
      motility control of rat gastric fundus, M1 receptors being more important.

PMID- 9183082
TI  - Viral transmission by blood products: a perspective of events covered by the
      recent tribunal of enquiry into the Irish Blood Transfusion Board.
AB  - The recent Tribunal of Enquiry into the Irish Blood Transfusion Board considered
      the transmission of the Hepatitis C virus (HCV) from the Irish perspective,
      considering particularly the medico-legal aspects of the specific transmission of
      HCV by anti-Rhesus D immunoglobulin (anti-D) manufactured by the Irish Blood
      Transfusion Service Board. However, there have been many other transmission
      episodes of HCV by intravenous immunoglobulin (IVIG) preparations and this brief
      review on the viral safety of immunoglobulin preparations considers the wider
      aspects of HCV transmission by immunoglobulin preparations.

PMID- 9183083
TI  - Fatalities from E. coli O157.

PMID- 9183084
TI  - Abdominal ascites.

PMID- 9183085
TI  - Stoma care management in the 1990s.

PMID- 9183087
TI  - Childhood sexuality--myths & dilemmas.

PMID- 9183086
TI  - Current management of acne.

PMID- 9183090
TI  - The impact of hospitalisation on prescribing costs for medical patients returning
      to the community.
AB  - As prescribed drugs represent an increasing expense in the health service, and
      prescribers assume more responsibility for costs, practitioners both in hospitals
      and the community are trying to define and limit this cost. We calculated drug
      costs in 107 consecutive medical admissions through the Accident and Emergency
      Department of admission and on discharge from hospital. The estimated (mean +/-
      SD) patient daily cost of drugs rose on admission from Pounds 0.90 +/- Pounds
      1.32 to Pounds 2.06 +/- Pounds 2.57 on discharge (p < 0.01) which was partly due
      to an increased number of drugs on discharge [4.6 +/- 3.0 compared with 2.8 +/-
      2.4 on admission (P < 0.01)]. However, the mean daily cost per item per patient
      also increased significantly from Pounds 0.23 +/- 0.30 to Pounds 0.38 +/- 0.39
      during hospitalisation (P < 0.002). This mean daily cost on discharge from
      hospital was not influenced by patient age or duration of hospital stay. These
      results confirm that patients on discharge from hospital are prescribed more
      drugs than on admission but each item on the prescription tends to be more
      expensive on discharge from hospital.

PMID- 9183088
TI  - Profile of patients attending a Dublin adolescent antenatal booking clinic.
AB  - A structured computer-coded questionnaire was administered to 120 consecutive
      teenage mothers attending a public adolescent antenatal clinic in order to
      examine their sociodemographic characteristics and sexual behaviour. The mean age
      of teenagers attending the clinic was 17.7 years (range: 14-19); only 5 (4.1%)
      were under 16 years. The mean gestation at booking was 16.4 weeks (range: 6.34);
      90 (75%) had unreliable menstrual dates; 29 (24.2%) were over 20 weeks, 18
      (68.9%) of these saying that they were afraid to attend hospital earlier. Ninety
      seven (80.8%) said that they had just one sexual partner to date and 105 (87.5%)
      said that they were involved in a continuing relationship with the father of the
      baby. Conception occurred within the first year of the relationship in 110
      (91.6%). One hundred and seventeen (88.2%) were from social classes III-V, 15
      (12.5%) were still at secondary school and 59 (49.2%) were unemployed. Of the 105
      (87.5%) who had left school 80% had not sat the Leaving Certificate and 10% had
      not undertaken any state examinations. Sixty seven (55.8%) continued to smoke and
      29 (24.2%) to drink alcohol during pregnancy. Sixty two mothers (51.7%) had used
      contraception in the past; only 33 (27.5%) had used it always. The age of first
      coitus, fertility awareness and the use of contraception were significantly
      influenced by social class and education. This study highlights the necessity for
      early commencement of sexual education programmes.

PMID- 9183089
TI  - Evidence for the polyp-cancer sequence in gallbladder cancer.
AB  - We report a patient with symptomatic biliary disease and who was diagnosed by
      ultrasound to have a large polypoid gallbladder lesion. Histopathology revealed
      adenoma in combination with carcinoma in situ. The evidence for the adenoma
      carcinoma sequence in gallbladder cancer and diagnostic and therapeutic
      implications are discussed.

PMID- 9183091
TI  - Can we increase breast feeding rates?
AB  - Breast feeding rates in Ireland have stagnated at around 33% over the past 10
      years. We aimed to assess the effect of a simple intervention in late pregnancy
      on breast feeding rates. The study was randomised and prospective. In the
      intervention group a sheet illustrating eight positive aspects of breast feeding
      was presented to mothers at their 36 week antenatal visit. This information was
      reinforced with a questionnaire on the topic of breast feeding. The control group
      received a routine antenatal care. There were 98 mothers in the intervention
      group and 95 controls. A similar percentage in each group had medical cards. On
      discharge from hospital 31.5% of controls and 43.9% of the test group were breast
      feeding. This difference just failed to reach statistical significance (P =
      0.07). The intervention, which took just three minutes of a medical student's
      time, appeared to result in an improved breast feeding rate. Though the
      difference did not reach statistical significance, this reflects, in part, the
      small numbers in the study. About half of the women in the study indicated that
      no doctor had offered any advice on the choice of feeding. Since this minor
      intervention produced a good response, it would seem appropriate to adopt a more
      positive attitude in the promotion of breast feeding.

PMID- 9183092
TI  - Unusual manifestations of type 1 autoimmune polyendocrinopathy.
AB  - We present a family with five members affected by Type 1 autoimmune
      polyendocrinopathy. All patients had chronic mucocutaneous candidiasis and dental
      abnormalities. Four patients had ocular abnormalities, four had
      hypoparathyroidism, and three had Addison's disease. The family was unusual in
      that all four affected females had premature ovarian failure. The ocular
      abnormalities included two patients with subcapsular lens opacities, one patient
      with asymptomatic corneal opacities, and one patient with severe bilateral
      iridocyclitis with cataract formation. One patient had pernicious anaemia and one
      had insulin dependent diabetes mellitus. All patients were negative on repeated
      occasions for organ specific and non-organ specific autoantibodies. Lymphocyte
      studies were performed in four patients. A deficiency of T suppressor cells was
      found in three and low normal levels were present in the fourth suggesting that
      the syndrome may be due to a defect in suppressor T cells.

PMID- 9183093
TI  - Use of seat belts in a Dublin area.
AB  - This study examines public compliance with seat belt regulations. Two busy
      suburbs in north Dublin were studied. Of the 2,139 vehicles surveyed 1,160
      (54.2%) drivers wore a seat belt. Young female drivers were most likely to comply
      with the regulations (70.1%). Only 344 (46.1%) front seat passengers wore their
      seat belt. 188 children who appeared to be under 10 years of age were observed in
      the front seat of vehicles and of those just 9 babies were appropriately
      restrained. Of the back seat passengers 108 (19.2%) wore seat belts; 99 (21.8%)
      children and 9 (9.8%) adults. Despite on-going publicity and progression in the
      regulations our use of seat belts is grossly disappointing. Road traffic
      accidents exert an unacceptably high toll on health in Ireland. Seat belts are
      known to be effective in preventing serious injury. A much greater emphasis on
      enforcement of legislation is now urgently needed to encourage responsible
      behaviour among vehicle users and to reduce the needless suffering due to road
      traffic accidents.

PMID- 9183094
TI  - Use of the AMS inflatable penile prosthesis in the management of erectile
      impotence.
AB  - Penile prostheses have become widely accepted in the management of erectile
      impotence. We report on 21 patients, aged from 22 and 65 years, who were
      implanted with AMS inflatable prostheses. Diabetes Mellitus, peripheral vascular
      disease, radical pelvic surgery and Peyronie's disease were among the most common
      aetiological factors in our patients. Psychogenic impotence was the indication
      for implantation in one patient. Two patients developed complications that
      required explantation of their devices. One additional patient who has a
      functioning device considers this form of assisted erection too artificial and
      has declined to use it for aesthetic reasons The AMS inflatable prosthesis
      effectively restores erectile function when initial conservative therapies have
      failed.

PMID- 9183095
TI  - Suicide in Ireland 1945-1992: social correlates.
AB  - Previous studies on suicide in Ireland have concentrated on the reliability of
      official suicide rates and there is a general consensus of opinion that there has
      been a genuine doubling of suicide in Ireland over the last two decades. The
      present study supports the view that there has been a true rise in Irish suicide
      rates and aims to examine some of the socio-demographic factors which might
      explain this rise. Indicators of anomie and lower integration in society were
      found to be associated with increased numbers of suicides. However, the
      relationship between suicide and other forms of personal violence is more
      complex.

PMID- 9183096
TI  - Hard of hearing and getting harder!

PMID- 9183097
TI  - Asthma, hay fever and eczema in Irish teenagers (ISAAC protocol).
AB  - The national prevalence of asthma, hay fever and eczema, employing the
      International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire,
      was determined during 1995 in 3148 Junior Certificate secondary school children
      aged 13-14 years throughout the Republic of Ireland. The prevalence values for
      asthma, hay fever and eczema were 15.2%, 24.8% and 9.4% respectively. Although
      5.4% reported having both asthma and hay fever, combinations of the other
      allergic conditions were less than 2%. Sex difference in prevalence rates for the
      various conditions occurred with asthma prevalence being higher for males, eczema
      in females, but hay fever was almost equally reported between males and females.
      This data documents the prevalence of teenage asthma with associated allergic
      conditions in the Republic of Ireland and will allow for present and future
      comparisons of these conditions with other countries world-wide using the ISAAC
      protocol.

PMID- 9183098
TI  - Eye injury and sport: sport-related eye injuries presenting to an eye casualty
      department throughout 1995.
AB  - A survey was undertaken of all patients attending the Eye Casualty Department at
      Waterford Regional Hospital with sports injuries in the twelve-month period 1st
      January 1995 to 31st December 1995. Ninety eight patients had problems associated
      with sport. Hurling was responsible for the largest group (30%) and football of
      different codes accounted for 29%. The next largest group was the racquet sports
      (13%). The most common injuries were to the anterior chamber (hyphaema and
      microhyphaema: 36%). There were three orbital fractures. 26 patients (27%) were
      admitted. 83 patients (85%) were male. The median age was 20 years. Sport is a
      significant cause of eye injury, which is often serious, and affects mostly young
      healthy males.

PMID- 9183099
TI  - Failed first trimester pregnancy in perspective.

PMID- 9183101
TI  - Systemic lupus erythematosus after thymectomy in a patient with myasthenia
      gravis.

PMID- 9183102
TI  - Faculty uninformed in the information age?

PMID- 9183104
TI  - Responsible education for today's professional nurses.

PMID- 9183103
TI  - International affairs. Some legal, ethical, and practical considerations for
      nurses who write.

PMID- 9183105
TI  - Doing history.

PMID- 9183106
TI  - Legal and ethical issues. Resuscitating clients against their wishes.

PMID- 9183107
TI  - Profile of administrators of schools of nursing, Part I: Resources for goal
      achievement.
AB  - Part one of a two-part study was conducted with administrators of schools of
      nursing to determine the perceived importance of various resources in their goal
      achievement. The deans and directors of the American Association of Colleges of
      Nursing member schools were mailed a questionnaire that included the scale of
      Sources of Influence and sections on personal and career characteristics. A
      response rate of 73.5 per cent was obtained. The most important resource was
      communication skills; 99.1 per cent of the subjects indicated that this resource
      was highly important. The top resources also included interpersonal skills,
      creativity in thinking, ability to mobilize groups, and intellectual ability. The
      results were remarkably similar to earlier studies that used different subject
      groups. Similarities in the rankings were noted in the top-ranked resources as
      well as the lower-ranked personal traits, work or professional organization
      positions, and mentoring. The resources that are of a supportive or prescribed
      nature appeared to be less important than the resources that can be controlled
      and developed. For nurse administrators, particular emphasis should be placed on
      the development and enhancement of communication skills and the other thinking
      and relating types of skills.

PMID- 9183108
TI  - Profile of administrators of schools of nursing, Part II: Mentoring relationships
      and influence activities.
AB  - Part two of a two-part study was conducted to obtain data on the influence
      activities and mentoring relationships of administrators of schools of nursing.
      The deans and directors of the American Association of Colleges of Nursing member
      schools were mailed a questionnaire that included sections on the above topics
      incorporated from Vance's questionnaire and a scale for rating mentoring
      functions. A response rate of 73.5 per cent was obtained. A majority of the
      subjects had entry-level preparation at the baccalaureate level and had obtained
      a doctorate. Despite a majority of the subjects reporting involvement in
      mentoring relationships, the percentage of those having a mentor while in the
      dean or director position was only 27 per cent. The positions of the mentors were
      most often supervisors from the academic area. A Student's t test determined that
      psychosocial functions of a mentoring relationship were more important than
      career functions, although both functions had a relatively high mean score. The
      subjects also reported involvement in a variety of professional activities of
      influence, such as publishing, presenting, consulting, and conducting research.
      The suggestion was made that perhaps multiple mentors and other avenues may be
      needed to prepare for the scholarly, professional, and administrative
      expectations of the role.

PMID- 9183109
TI  - Books on health policy and health reform: how is nursing represented?
AB  - The recent national debate on health care reform stimulated publication of a
      large number of books on the topic. A selected review of books published during
      the height of the health reform debate (1993 and 1994) is reported in this
      article. A total of 35 books written by authors from 13 different disciplinary
      perspectives were reviewed to determine how the nursing profession was
      represented in discussions of health system reform. The books were categorized
      according to title, author affiliation, purpose of the book, and the number and
      category of references to nursing. Seven categories of reference to nursing
      emerged from the analysis. Approximately on half of the books contained no
      references to nursing, 39 per cent had less than 10 references to nursing, and
      only four books had more than 10 references to nursing. The books with the
      greatest number of references were further analyzed and compared regarding
      thematic presentation of reform issues. A discussion of the importance of
      documentation of nursing in the health policy process, along with recommendations
      for improved dissemination of nursing perspectives for a redesigned health care
      system, is included.

PMID- 9183110
TI  - Assessing substance abuse among health care students and the efficacy of
      educational interventions.
AB  - Approximately 10 per cent of nurses are chemically dependent, and, for many,
      substance abuse begins while attending nursing school. Faculty must be able to
      assess the extent of the problem, understand the contributing factors, recognize
      signs and symptoms, and use educational interventions in identifying and
      preventing chemical dependency in nurses. Beginning in 1989, the authors sampled
      all entering students in four colleges on a health science campus using the
      Standardized Substance Abuse Attitude Survey and obtained resurvey data from two
      of the colleges' 1989 entering classes in fall 1991. Each college developed
      educational interventions. Some clear differences between nursing and pharmacy
      students emerged and indicated that a greater emphasis on drug and alcohol
      education can pay dividends. Establishing a data base over a period of more than
      2 years provides a foundation to evaluate further interventions.

PMID- 9183111
TI  - The essence of partnership in research.
AB  - The essence of working together in research was explored using a two-step
      ethnomethodological approach. First, the authors reflectively analyzed their own
      7-year partnership. This was followed by a collective interpretive process of
      interviewing other doctorally prepared health care researchers who were working
      in partnerships. Core constructs were identified in the reflective process and
      validated and expanded in the collective analysis, and variations were
      identified. Dialogue was the basis for maintaining the relationship, and all
      agreed that trustworthiness, competence, and flexibility were necessary
      requisites for individuals in a partnership. Successful relationships were
      characterized by acceptance, validation, commitment, synergy, and fun. Benefits
      of working together include increased productivity, quality, and personal growth.
      Hindrances to successfully working together were identified as problems centered
      around maturity, ownership, and control issues.

PMID- 9183112
TI  - Verbal abuse of staff nurses by physicians.
AB  - The prevalence and consequences of verbal abuse of staff nurses by physicians
      were examined in the context of Lazarus' stress-coping model. Of the 130 staff
      nurses completing a mailed Verbal Abuse Questionnaire, 90 per cent reported
      experiencing at least one episode of verbal abuse during the past year. The
      average number of reported incidents during the year was between 6 and 12. The
      most frequent and most stressful types of verbal abuse came in the forms of
      abusive anger, ignoring, and condescension. Nurses tended to interpret the abuse
      in an adaptive fashion, e.g., they viewed the abusing physician as someone with a
      problem and perceived themselves as not deserving the abuse. They used a variety
      of adaptive palliative as well as problem-focused coping skills. The most severe
      long-term effects of verbal abuse were a negative relationship with the offending
      physician and negative effects on job satisfaction. These findings show clearly
      that verbal abuse of nurses by physicians continues to exist and is associated
      with negative consequences on their personal as well as professional well-being.
      Nurse and physician educators as well as nurse administrators must address this
      problem through educational activities as well as protective hospital policies.

PMID- 9183113
TI  - Client satisfaction: traditional care versus cluster care.
AB  - The purposes of this study were to describe and compare the level of satisfaction
      of clients receiving traditional care and those receiving cluster care. None of
      the studies reviewed described client satisfaction in the traditional and cluster
      care service delivery models using a reliable and valid instrument. The study
      sample consisted of 77 Medicaid-eligible elderly clients from three different
      home care agencies in an urban city. Of the 77 subjects, 37 (48 per cent)
      received cluster care, and 40 (52 percent) received traditional care. After
      receiving approval from the home health care agencies, subjects who agreed to
      participate in the study were asked to sign a consent form and to complete a
      demographic data sheet and the Gray's Home Care Satisfaction Scale (GHCSS).
      Internal consistency reliability for the GHCSS is 0.78, with content validity
      present. An independent student's t test showed a statistically significant
      difference in the level of satisfaction of clients receiving traditional care and
      cluster care (t = -5.27, P = .0005). Clients receiving traditional care had
      higher levels of satisfaction than clients receiving cluster care. Additional
      findings showed that men in both the traditional and cluster care groups were
      more satisfied than women (t = -3.19, P = .003 and t = -2.96, P = .007,
      respectively). Analysis of variance showed that blacks in both the traditional
      and cluster care groups had lower levels of satisfaction than either whites or
      Hispanics. Implications of study findings are discussed.

PMID- 9183115
TI  - Memory deficits in schizophrenia: inadequate assimilation or true amnesia?
      Findings from the Wechsler Memory Scale--revised.
AB  - Researchers disagree about why patients with schizophrenia perform poorly on
      memory tests. Some argue the presence of a fundamental memory deficit stemming
      from dysfunction in medial temporal lobe structures, principally the hippocampus.
      Others, stressing the contributions of impaired attention or executive failings
      such as a disorganized approach to learning, implicate larger neural networks. We
      compared data from psychometrically similar procedures, the Wechsler Memory Scale
      Revised (WMS-R) and Wechsler Adult Intelligence Scale-Revised (WAIS-R), generated
      by 17 schizophrenia-spectrum patients and 33 psychiatric controls. We then
      compared our findings in detail with all published WMS-R/WAIS-R schizophrenia
      data. Our findings and the literature indicate that the acquisition of new
      information is disrupted in schizophrenia, but they provide little support for
      claims that memory deficits are especially pronounced relative to other
      weaknesses. Since schizophrenia patients exhibit reasonable retention following
      intervening activity, theories that place primary emphasis upon hippocampal
      dysfunction are not well supported.

PMID- 9183114
TI  - What we don't know about over-the-counter analgesics.

PMID- 9183116
TI  - Distractibility and symptoms in schizophrenia.
AB  - Distractibility was assessed in 59 inpatients with a relapse of schizophrenia and
      3 mo later during a period of relative remission. Distractibility was measured
      with a digit span task and symptoms with the Positive and Negative Syndrome Scale
      (PANSS). Although positive and negative symptoms improved significantly, the
      schizophrenia subjects' performance on the digit span task remained stable over
      time. There was no relationship between attention and symptoms. The possibility
      of distractibility being a vulnerability indicator for schizophrenia is
      discussed.

PMID- 9183118
TI  - Pregnancy outcome and neurodevelopment of children exposed in utero to
      psychoactive drugs: the Motherisk experience.
AB  - This paper presents an overview of the Motherisk Program data on pregnancy
      outcome and neurodevelopment of children exposed in utero to selected
      psychoactive drugs. First, the use of cocaine during pregnancy has been
      associated with increased risk of spontaneous abortions, abruptio placenta,
      premature labor, and stillbirth. Twenty-three adopted children exposed in utero
      to cocaine demonstrated an 8-fold increase in risk for microcephaly compared with
      controls. Global intelligence quotients (IQ) did not differ between the 2 groups,
      but the cocaine-exposed children achieved significantly lower scores on the
      Reynell language test. Second, the long-term neurobehavioral effects of fetal
      alcohol syndrome (FAS) were studied in 384 children to show that alcohol-induced
      brain insults, which consist of attention and memory deficits together, and poor
      adaptability and organization are not attenuated with age. Third, the rates of
      major malformations in children exposed in utero to fluoxetine, tricyclic
      antidepressants, and nonteratogenic drugs did not differ or exceed the expected
      rates in the general population. A 2nd phase of this study established the safety
      of antidepressants during pregnancy by demonstrating that the mean IQ and
      language scores are comparable in the 3 groups. A level 2 ultrasonography is
      recommended in cases of in utero exposure to lithium and carbamazepine because of
      an increased risk of cardiac malformations and spina bifida, respectively.

PMID- 9183117
TI  - Brain 5-hydroxytryptamine uptake sites labeled with [3H]paroxetine in
      antidepressant drug-treated depressed suicide victims and controls.
AB  - Saturation binding of [3H]paroxetine was performed in 10 brain regions from a
      group of suicide victims who had a firm, retrospective diagnosis of depression
      and who had been prescribed antidepressant drugs, as well as in a group of
      controls. The number of binding sites did not differ significantly between
      suicide victims and controls, apart from in putamen, where a lower number of
      sites was found in the suicide victims. Higher dissociation constant (Kd) values
      were found in suicide victims dying by antidepressant overdose and also in those
      dying by other means when compared with controls.

PMID- 9183119
TI  - Toxicity in venlafaxine overdose.

PMID- 9183120
TI  - BPD and ADHD.

PMID- 9183121
TI  - Thought disorder in BPD and ADHD.

PMID- 9183123
TI  - Obsessive difficult temperament.

PMID- 9183122
TI  - Paroxetine-induced mania.

PMID- 9183124
TI  - The swivel chair test.

PMID- 9183125
TI  - Treatment for kleptomania.

PMID- 9183126
TI  - Pharmacology of the selective serotonin reuptake inhibitors in children and
      adolescents.
AB  - OBJECTIVE: To review the pharmacology of a new class of medications, the potent
      selective serotonin reuptake inhibitors (SSRIs), what is known about their
      metabolism in children and adolescents, and the practical clinical implications
      of such. METHOD: Articles were retrieved through index Medicus searches for
      articles published during the past 10 years on the SSRIs and on pediatric
      pharmacology. RESULTS: More than 300 articles were reviewed. Pharmacological
      data, derived from relevant adult literature, were summarized and extrapolated to
      children and from the limited pediatric literature. The SSRIs represent a new
      class of antidepressants with distinct advantages in their side effect profile
      and their broad therapeutic index over that seen with the tricyclic
      antidepressants. Their advantage of few anticholinergic side effects and limited
      cardiovascular toxicities are particularly relevant for the pediatric population.
      The SSRIs are metabolized via the hepatic cytochrome isoenzyme P450 system, and
      potential drug-drug interactions are reviewed. CONCLUSIONS: The SSRIs appear to
      offer advantages over the tricyclic antidepressants. Unfortunately,
      pharmacokinetic data are lacking, and systematic studies of safety and efficacy
      in the pediatric age group are limited. Preliminary reports are encouraging, but
      further study is required.

PMID- 9183127
TI  - Attention-deficit hyperactivity disorder: a category or a continuum? Genetic
      analysis of a large-scale twin study.
AB  - OBJECTIVE: To investigate heritability and continuum versus categorical
      approaches to attention-deficit hyperactivity disorder (ADHD), using a large
      scale twin sample. METHOD: A cohort of 1,938 families with twins and siblings
      aged 4 to 12 years, recruited from the Australian National Health and Medical
      Research Council Twin Registry, was assessed for ADHD using a DSM-III-R-based
      maternal rating scale. Probandwise concordance rates and correlations in
      monozygotic and dizygotic twins and siblings were calculated, and heritability
      was examined using the De Fries and Fulker regression technique. RESULTS: There
      was a narrow (additive) heritability of 0.75 to 0.91 which was robust across
      familial relationships (twin, sibling, and twin-sibling) and across definitions
      of ADHD as part of a continuum or as a disorder with various symptom cutoffs.
      There was no evidence for nonadditive genetic variation or for shared family
      environmental effects. CONCLUSIONS: These findings suggest that ADHD is best
      viewed as the extreme of a behavior that varies genetically throughout the entire
      population rather than as a disorder with discrete determinants. This has
      implications for the classification of ADHD and for the identification of genes
      for this behavior, as well as implications for diagnosis and treatment.

PMID- 9183128
TI  - Attention-deficit hyperactivity disorder dimensions: a twin study of inattention
      and impulsivity-hyperactivity.
AB  - OBJECTIVE: This study used a model-fitting strategy to estimate genetic and
      environmental contributions to the core behavioral dimensions associated with
      attention-deficit hyperactivity disorder (ADHD) in 576 twin boys, aged 11 and 12
      years. METHOD: Teacher ratings and maternal structured interview reports composed
      of behavioral items including DSM-III and DSM-III-R criteria for ADHD were
      obtained for 194 pairs of monozygotic and 94 pairs of dizygotic twins. Factor
      analysis of these measures yielded two ADHD-related dimensions, inattention and
      impulsivity-hyperactivity. Scales representing these dimensions were used in the
      genetic analyses. RESULTS: Univariate analyses supported a substantial
      contribution of genetic factors in the expression of inattention and impulsivity
      hyperactivity and smaller contributions of shared and nonshared environmental
      factors. Results varied according to informant source, with mothers' reports
      suggestive of rater bias effects. Bivariate analyses indicated that the
      correlation between these two ADHD dimensions was also genetically mediated.
      CONCLUSIONS: Genetic factors are etiologically important in the expression of the
      separate dimensions of ADHD and in the covariation between them. However, it is
      important to obtain reports from more than one informant because rater bias
      effects may be operative, particularly in maternal reports.

PMID- 9183129
TI  - Behavioral, situational, and temporal effects of treatment of ADHD with
      methylphenidate.
AB  - OBJECTIVE: To determine the behavioral, situational, and temporal effects of 4
      months of methylphenidate (MPH) treatment for attention-deficit hyperactivity
      disorder (ADHD). METHOD: Ninety-one children with ADHD were randomly assigned to
      receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a
      placebo. Treatment effects were investigated with measures sensitive to various
      behaviors (core and associated symptoms), situations (home and school), time
      periods (morning and afternoon, after reaching the target dose, and after 4
      months of treatment), and side effects. RESULTS: MPH treatment improved symptoms
      of ADHD and oppositional behavior at school, both in the morning and afternoon,
      but not at home. Side effects (increase in physiological and effective symptoms,
      lack of weight gain) were significantly more frequent with MPH than with placebo
      treatment. Benefit was evident after titration, but the onset of some side
      effects was delayed. Side effects were reported by parents but not by teachers.
      CONCLUSIONS: Positive effects of MPH on behavior are evident in the classroom,
      but with MPH given twice daily, parents do not report that MPH improves behavior
      at home. Greater impact on home behavior may require three times daily MPH and
      combined treatments.

PMID- 9183130
TI  - Gay and lesbian issues in child and adolescent psychiatry training as reported by
      training directors.
AB  - OBJECTIVE: Although increased evidence of disproportionate psychosocial risk and
      other health problems encountered by lesbian, gay male, and bisexual (LGB) youths
      has emerged, no study has described how the topic of homosexuality is addressed
      within child and adolescent residency psychiatry training. METHOD: Residency
      training directors in U.S. child and adolescent psychiatry programs were asked
      questions about instruction on the topic of homosexuality and the care of LGB
      patients, the department's view of whether homosexuality represents a
      pathological condition, the director's awareness of LGB colleagues and residents,
      and the director's opinion of LGB residents' disclosure of their homosexuality to
      their patients and patients' families. Asking similar questions facilitated a
      comparison of survey results with those of an earlier study of general psychiatry
      training directors. RESULTS: The reported departmental attitudes about whether
      homosexuality represents a pathological condition were essentially equivalent in
      general and child programs. Child and adolescent training directors were,
      however, less likely to have a favorable view of disclosure of sexual orientation
      to patients, less likely to know LGB residents or faculty, and less likely to
      report LGB residents an asset to their departments. CONCLUSIONS: The prediction
      that the majority of child and adolescent training programs would reflect a
      heightened awareness of the vulnerability of LGB youths was not confirmed.

PMID- 9183131
TI  - Hospitalizing the suicidal adolescent: decision-making criteria of psychiatric
      residents.
AB  - OBJECTIVE: The primary purpose of this research is to investigate the criteria
      used by general psychiatric residents in determining the appropriateness of
      hospitalization. METHOD: A questionnaire containing 64 vignettes describing
      adolescent suicide attempts was completed by a sample of 33 residents from a
      general psychiatry training program. Six variables known to relate to lethality
      of attempt were systematically varied within the vignettes: gender, depression,
      conduct disorder/substance abuse, previous attempts, suicidal relative, and
      family supports. Respondents were asked to judge the appropriateness of
      hospitalization for each vignette. RESULTS: Hospitalization preference was
      significantly predicted by all risk factors except for gender, with the presence
      of depression emerging as the most important predictor of hospitalization.
      Residents recommended hospitalization more frequently than did experienced child
      and adolescent clinicians. In comparison with experienced clinicians, residents
      placed more importance on depression, and less importance on conduct
      disorder/substance abuse, in making decisions to hospitalize. CONCLUSIONS:
      Although psychiatric residents use known risk factors for adolescent suicide in
      assessing need for hospitalization, there was clear support for further training
      initiatives for psychiatric residents concerning the assessment of suicidal
      adolescents.

PMID- 9183132
TI  - First-episode major depressive and dysthymic disorder in childhood: clinical and
      sociodemographic factors in recovery.
AB  - OBJECTIVE: To characterize the temporal pattern of depressive disorder in
      childhood, the first episode of depression was examined, focusing on recovery and
      its baseline predictors. METHOD: The sample includes 112 clinically referred 8-
      to 13-year-olds with first-episode major depressive or dysthymic disorder
      participating in a naturalistic follow-up study. Psychiatric diagnoses were based
      on standardized interviews and operational criteria. Recovery was modeled by
      multivariate procedures using baseline clinical and demographic predictors.
      RESULTS: Recovery rates were 86% and 7% for major depression and dysthymia,
      respectively, 2 years after onset. Median duration of major depression was 9
      months and was predicted only by underlying dysthymia. Median duration of
      dysthymic disorder was 3.9 years and was predicted only by comorbid externalizing
      disorder. In post hoc analyses, no positive treatment effects were detected.
      CONCLUSIONS: First-episode depression in youths is persistent, it generally
      appears to run its own course, and its naturalistic treatment requires scrutiny.
      However, because comorbid externalizing disorder apparently affects duration of
      dysthymia, intervention for behavior problems may shorten this type of
      depression.

PMID- 9183133
TI  - Recurrence of major depressive disorder in hospitalized children and adolescents.
AB  - OBJECTIVE: To evaluate the outcome of a sample of children and adolescents
      hospitalized with major depressive disorder (MDD) and to assess different
      duration and severity criteria to define recovery and recurrence. METHOD: Fifty
      nine of 70 children and adolescents were reevaluated 1 to 5 years later, and the
      intervening course of depression and other disorders was assessed using the
      Kiddie-Longitudinal interval Follow-up Evaluation (K-LIFE). RESULTS: Ninety-eight
      percent of subjects had recovered from their index MDD episode within 1 year of
      their initial evaluation, but 61% had at least one recurrence during the follow
      up period. Of those with recurrences, 47.2% had a recurrence within 1 year and
      69.4% by 2 years from the offset of the index episode. Changing the criteria for
      recovery by increasing the length of time required to define recovery resulted in
      decreases in the number of episodes of recurrence reported. CONCLUSION: MDD in
      children and adolescents is often an episodic disorder. Difference in definitions
      of recovery and recurrence affect the data reported. Consistent definitions of
      remission, recovery, relapse, and recurrence are needed. These data suggest that
      recovery may be defined after two consecutive months without symptoms and that
      episodes of MDD may be briefer, but more frequent, in children and adolescents
      than in adults.

PMID- 9183134
TI  - Affect regulation and suicide attempts in adolescent inpatients.
AB  - OBJECTIVE: To examine the relationship between affect dysregulation and self
      destructive behaviors in adolescent suicide attempters. METHOD: Measures of
      affect dysregulation, number of risk-taking behaviors in past year, presence of
      self-mutilative behaviors in past year, and number of different types of self
      mutilative behaviors in past year were individually administered to adolescents
      admitted to an inpatient unit who were either suicide ideators (n = 25) or
      suicide attempters (n = 35). RESULTS: Suicide attempters reported significantly
      higher levels of affect dysregulation and a greater number of different types of
      self-mutilative behaviors in the past year than suicide ideators. In addition,
      the number of different types of self-mutilative behaviors in the past year had
      the strongest relationship to suicide attempts. CONCLUSION: Suicidal behavior
      among adolescent psychiatric patients is related to poor affect regulation. A
      risk factor for suicidal behavior in adolescents is a broad range of self
      mutilative acts in the year preceding the suicide attempt.

PMID- 9183136
TI  - An epidemiological study of the use of ECT in adolescents.
AB  - OBJECTIVE: There is little knowledge about the use of electroconvulsive therapy
      (ECT) in adolescents. Given the prevalence and severity of psychiatric disorders
      in this age group, it is important to determine the frequency, indications,
      effectiveness, and side effects of ECT. METHOD: Persons younger than 19 years who
      received ECT between 1990 and 1996 in the Australian state of New South Wales
      were identified. Detailed information about diagnosis, treatment, and outcome was
      then obtained. RESULTS: Forty-two patients aged 14 to 18 years underwent a total
      of 49 courses comprising 450 ECTs (0.93% of all treatments given to all persons).
      Marked improvement or resolution of symptoms occurred in half of the completed
      courses. Mood disorders derived most benefit from ECT. Side effects were
      transient and minor. Prolonged seizures were observed in 0.4% of treatments.
      Comorbid personality disorder predicted poorer response, and the anesthetic
      propofol was associated with shorter seizures. CONCLUSIONS: Although ECT is an
      effective treatment for some mental disorders in adolescents and has few side
      effects, it is seldom used. Indications, response, and unwanted effects were
      similar to those observed in adults. The use of propofol may reduce the risk of
      prolonged seizures.

PMID- 9183135
TI  - Adolescent physical abuse and suicide attempts.
AB  - OBJECTIVE: The rate of suicide attempts and the exposure to risk factors for
      suicide in an unselected sample of confirmed cases of physically abused
      adolescents recruited directly from the New York State Central Register for
      Nassau and Suffolk Counties was compared with those of a community sample of
      nonabused adolescents. METHOD: Semistructured and structured diagnostic
      interviews were used in the assessment of psychopathology of adolescents and
      their parents RESULTS: The proportion of adolescents attempting suicide did not
      differ for the two groups. However, the abused adolescents showed significantly
      greater exposure to risk factors for adolescent suicide, including family
      disintegration, and diagnoses of depression, disruptive behavior disorders, and
      substance abuse and dependence. Comparisons of the 8 physically abused
      adolescents who attempted suicide with the 91 who did not attempt suicide showed
      that the following factors were associated with significantly greater risk for
      suicide attempts: adolescents' perceptions of their families as lacking
      cohesiveness and maternal support, higher adolescent "hostility" ideation scores,
      adolescent diagnoses of disruptive disorders and conduct disorders, adolescent
      substance abuse/dependence, and exposure to a suicide attempt by a family member
      or a friend. CONCLUSION: A transactional model of abuse, family and personal
      stressors, and the development of adolescent vulnerability leading to
      psychopathology is offered to explain the results.

PMID- 9183137
TI  - A controlled trial of light therapy for the treatment of pediatric seasonal
      affective disorder.
AB  - OBJECTIVE: To evaluate the efficacy of light therapy for the treatment of
      pediatric seasonal affective disorder (SAD). METHOD: 28 children (aged 7 to 17
      years) at two geographically distinct sites were enrolled in a double-blind,
      placebo-controlled, crossover trial of bright-light treatment. Subjects initially
      entered a week-long baseline period during which they wore dark glasses for an
      hour a day. They were then randomly assigned to receive either active treatment
      (1 hour of bright-light therapy plus 2 hours of dawn simulation) or placebo (1
      hour of clear goggles plus 5 minutes of low-intensity dawn simulation) for 1
      week. The treatment phase was followed by a second dark-glasses phase lasting 1
      to 2 weeks. After this phase, the children received the alternate treatment.
      Response was measured using the parent and child versions of the Structured
      Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective
      Disorders version (SIGH-SAD). RESULTS: Data were analyzed as change from
      baseline. SIGH-SAD-P total depression scores were significantly decreased from
      baseline during light therapy compared with placebo (one-way analysis of
      variance, rho = .009), and no differences were found between the placebo and
      control phases. Subscores of atypical and typical depression were also
      significantly decreased during the active treatment (rho = .004 and .028,
      respectively). A similar trend was noted with the SIGH-SAD-C, but this did not
      reach significance. At the end of the study, 78% of the parents questioned and
      80% of the children questioned rated light therapy as the phase during which the
      child "felt best." CONCLUSION: Light therapy appears to be an effective treatment
      for pediatric SAD.

PMID- 9183138
TI  - Case study: the use of melatonin in a boy with refractory bipolar disorder.
AB  - The authors describe the clinical course of a 10-year-old boy with bipolar
      disorder diagnosed at age 5 years. Lithium, carbamazepine, and valproic acid were
      ineffective or caused intolerable side effects. A trial of melatonin led to rapid
      relief of insomnia and aborted a manic episode. He has continued to take
      melatonin and adjunctive alprazolam for 15 months without recurrence of insomnia
      or mania. Affective disorders involving circadian dysregulation may respond to
      interventions that restore a normal sleep-wake cycle. Literature supporting this
      hypothesis is cited.

PMID- 9183139
TI  - A pilot study of nadolol for overt aggression in developmentally delayed
      individuals.
AB  - OBJECTIVE: The aim of this preliminary pilot study was to investigate the safety
      and efficacy of open-label nadolol as an adjunctive pharmacological treatment for
      aggression and/or inattention/overactivity in a developmentally delayed child,
      adolescent, and young adult population. METHOD: Twelve subjects enrolled and
      completed (mean age 13.8 years, range 9 through 24) a 5-month, open, prospective
      protocol of nadolol (mean dose 109 mg, range 30 through 220 mg) with systematic
      baseline and outcome evaluations and weekly clinical assessment. RESULTS: All
      subjects were developmentally delayed and most were cognitively delayed. Ten
      subjects (83%) showed clinical improvement while receiving nadolol. Significant
      improvements were noted on observer-rated overt categorical aggression, severity
      of illness, and global impressions of improvement. No significant effects were
      found for inattention/overactivity. Nadolol was well tolerated, with few side
      effects. CONCLUSIONS: Overt categorical aggression presenting in developmentally
      delayed children, adolescents, and young adults may respond to nadolol treatment.

PMID- 9183140
TI  - Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal
      study.
AB  - OBJECTIVE: To report results from a long-term prospective study of safety of
      haloperidol treatment and prevalence of haloperidol-related dyskinesias. METHOD:
      Subjects were children with autism requiring pharmacotherapy for target symptoms.
      After baseline assessments, children received haloperidol treatment; responders
      requiring further treatment were considered for enrollment into the present
      study. Six-month haloperidol treatment periods were followed by a 4-week placebo
      period. The procedure was repeated if further haloperidol treatment was required.
      At specified times children were evaluated by using multiple instruments.
      RESULTS: Between 1979 and 1994, 118 children aged 2.3 to 8.2 years participated
      in the study. The mean dose of haloperidol was 1.75 mg/day. Mainly withdrawal
      dyskinesias (WD) developed in 40 (33.9%) children; 20 had more than one
      dyskinetic episode. A subgroup that remained significantly longer in the study
      and had a significantly higher cumulative dose of haloperidol evidenced a
      significantly higher incidence of WD. Occurrence rates of tardive dyskinesia (TD)
      and multiple episodes of TD/WD were higher among girls. CONCLUSION: Female gender
      and pre- and perinatal complications may be involved in susceptibility to
      dyskinesias; greater cumulative haloperidol dose and/or longer exposure to
      haloperidol may increase the risk.

PMID- 9183141
TI  - Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity.
AB  - OBJECTIVE: To evaluate the reliability and validity of a semistructured measure
      of obsessive-compulsive symptom severity in children and adolescents with
      obsessive-compulsive disorder (OCD). METHOD: Sixty-five children with OCD (25
      girls and 40 boys, aged 8 to 17 years) were assessed with the Children's Yale
      Brown Obsessive Compulsive Scale (CY-BOCS). Interrater agreement was assessed by
      four raters in a subsample (n = 24). Discriminant and convergent validity were
      assessed by comparing CY-BOCS scores to self-ratings of depression, anxiety, and
      obsessive-compulsive symptoms. RESULTS: Internal consistency was high, measuring
      .87 for the 10 items. The intraclass correlations for the CY-BOCS Total,
      Obsession, and Compulsion scores were .84, .91, and .68, suggesting good to
      excellent interrater agreement for subscale and total scores. The CY-BOCS Total
      score showed a significantly higher correlation with a self-report of obsessive
      compulsive symptoms (r = .62 for the Leyton survey) compared with the Children's
      Depression Inventory (r = .34) and the Children's Manifest Anxiety Scale (r =
      .37) (p = .02 and .05, respectively). CONCLUSIONS: The CY-BOCS yields reliable
      and valid subscale and total scores for obsessive-compulsive symptom severity in
      children and adolescents with OCD. Reliability and validity appear to be
      influenced by age of the child and the hazards associated with integrating data
      from parental and patient sources.

PMID- 9183143
TI  - On teenagers and tattoos.

PMID- 9183142
TI  - Magnetic resonance imaging of children without sedation: preparation with
      simulation.
AB  - OBJECTIVE: It was hypothesized that a scanner simulator that replicates the
      magnetic resonance imaging (MRI) environment could be used to prepare pediatric
      subjects for successful completion of a diagnostic-quality MRI examination
      without pharmacological sedation. METHOD: Sixteen healthy children, 6 to 17 years
      of age, were matched for age and sex with 16 psychotropic medication-naive
      children with obsessive-compulsive disorder. Distress was measured throughout
      simulation and scanning procedures using heart rate and a self-report distress
      scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual
      MRI scanning procedure but did not undergo the simulation scanning procedure.
      RESULTS: Significant decreases in heart rate and self-reported distress level
      were observed in all subjects during the simulator session that were maintained
      to the end of the actual scanner experience. All subjects successfully completed
      MRI examinations without chemical restraint. Subjects who were not trained in the
      simulator had higher heart rates and self-reported distress levels in the actual
      scanner than did simulation-trained subjects. CONCLUSIONS: Simulation without
      pharmacological sedation successfully prepared pediatric subjects in this pilot
      study for high-quality MRI studies. Subject preparation may be an alternative
      procedure to sedation for routine MRI examination in healthy and anxious children
      6 years of age and older.

PMID- 9183145
TI  - [Evaluation of myocardial perfusion by 99mTc-tetrofosmin SPECT before and after
      emergent percutaneous transluminal coronary angioplasty for acute myocardial
      infarction].
AB  - To assess clinical performance of coronary perfusion in patients with acute
      myocardial infarction following successful PTCA, various 99mTc-tetrofosmin (TF)
      SPECT were obtained. Twenty-eight patients with acute myocardial infarction
      underwent TF SPECT before emergent PTCA (acute phase), after 7 days (subacute
      phase) and 4 weeks (chronic phase) later. Twenty-eight patients divided into 2
      groups. Early group; time lug from onset of AMI till PTCA is 6 hours or shorter
      (n = 17), delayed group; time lug is more than 6 hrs (n = 11). The defect scores
      were graded by 4 points grading system (0 as normal to 3 as defect) in 14
      myocardial segments. In early group, the mean defect score was 13 +/- 7 at acute
      phase, 6 +/- 5 at subacute phase, and 3 +/- 4 at chronic phase. In delayed group,
      the mean value of defect score at each phases were 18 +/- 7, 14 +/- 7, and 13 +/-
      7. The improvement of defect score of early group was significantly larger than
      that of delayed group (p < 0.005). These data indicate that PTCA therapy for
      acute MI patients is useful particularly in the early stage following acute MI.

PMID- 9183144
TI  - [Usefulness of 201Tl/123I-BMIPP myocardial SPECT to evaluate myocardial viability
      and area at risk in acute myocardial infarction--comparison with 201Tl/99mTc-PYP
      dual SPECT].
AB  - To evaluate the area at risk and the myocardial viability of acute myocardial
      infarction (AMI), we compared rest 123I-beta-methyl iodophenyl pentadecanoic acid
      (123I-BMIPP) and 201Tl myocardial SPECT with 201Tl/99mTc-PYP dual SPECT (D-SPECT)
      in 65 patients (mean age 64 +/- 11 years) with AMI. D-SPECT was performed in 3 to
      5 days, 123I-BMIPP myocardial SPECT in 5 to 7 days, and left ventriculography on
      1 month after onset of AMI. Furthermore, 201Tl/123I-BMIPP myocardial SPECT and
      left ventriculography were performed on 4 months after onset of AMI. The area
      which showed the reduced 123I-BMIPP uptake was larger than that showed the
      accumulation of 99mTc-PYP. The improvement of regional wall motion on 4 months
      after onset of AMI tended to be more closely correlated with the existence of
      discrepancy zone between 201Tl and 123I-BMIPP uptake than that of overlap zone
      between 201Tl and 99mTc-PYP uptake in acute period. We conclude that 201Tl/123I
      BMIPP myocardial SPECT is more useful to evaluate the area at risk and myocardial
      viability of AMI than D-SPECT.

PMID- 9183146
TI  - [Importance of the delayed 123I-BMIPP image for detecting myocardial metabolic
      abnormality induced by transient myocardial ischemia: a case of vasospastic
      angina].
AB  - We experienced a case of 64-year-old man with stunned myocardium caused by
      vasospasm. Without enzymatic evidence of an acute myocardial infarction, the
      patient developed a prolonged chest pain with ST elevation in the
      electrocardiogram in the midnight before the day of coronary angiography.
      Coronary angiogram revealed no significant stenosis and left ventriculography
      demonstrated akinesis in the apico-anteroseptal region. Although initial images
      of 123I-BMIPP myocardium SPECT showed no significant decrease of uptake, delayed
      images revealed marked decrease of tracer uptake in the apico-anteroseptal region
      in which left ventriculography showed abnormal wall motion. After 3 months of
      medication, left ventriculography disclosed a marked improvement, and coronary
      spasm was evoked in the proximal portion of left anterior descending artery after
      intracoronary ergonovine provocations. At the same time, both initial and delayed
      images of 123I-BMIPP myocardial SPECT showed no significant decrease of tracer
      uptake. This patients was considered as a noteworthy case to understand the
      kinetics and metabolism of 123I-BMIPP in stunned myocardium.

PMID- 9183147
TI  - [Assessment of left ventricular systolic function derived from ECG-gated
      myocardial SPECT with 99mTc-tetrofosmin: automatic determination of LV epi- and
      endocardial surface].
AB  - Non-invasive assessment of ischemic heart disease requires information of both LV
      function and myocardial perfusion. Recently, ECG-gated myocardial SPECT with
      technetium-labeled radiopharma-ceuticals can provide both of them. Gated
      myocardial SPECT were performed in thirty-three patients with cardiac disease
      using a two-headed rotating gamma camera system (ADAC; VERTEX), 30-60 minutes
      after resting injection of 555-740 MBq of 99mTc-Tetrofosmin. Then, the SPECT data
      were used to determine the LV epi- and endocardial surface, and LV volume for
      measurement of LVEF was calculated automatically. This entire computational
      process required only 210 seconds per 16 frame study. Interobserver agreement of
      EF values obtained from gated SPECT was excellent (r = 0.996, n = 10, p < 0.01).
      LVEFs obtained from gated SPECT showed good correlation to those calculated from
      radionuclide ventriculography (MUGA) (r = 0.91, p < 0.01). In conclusion, this
      automatic method using gated myocardial SPECT data was considered to be useful
      for assessment of LV function with reproducibility.

PMID- 9183149
TI  - [Compton-scatter correction using the triple energy window (TEW) method in
      conventional single photon emission computed tomography without TEW acquisition
      hardware].
AB  - We devised a method which allowed the triple energy window (TEW) method to be
      applied for Compton-scatter correction in conventional single photon emission
      computed tomography (SPECT) systems without any hardware for TEW acquisition. In
      this method, the data within two subwindows located at both sides of the main
      window were acquired together. The effectiveness of this method was investigated
      by phantom experiments. The integral and differential uniformities measured using
      a flood phantom filled with 123I were minimized when the energy width of
      subwindows was 5 keV (5.8% and 4.2%, respectively). When this method was applied
      to a brain phantom filled with 123I in which the relative activities in white and
      gray matter were assigned as 1: 4.3, the ratio of SPECT values between them was
      more accurate (1:4.26) than that obtained without this method (1:208). This
      method appears to be useful for Compton-scatter correction in SPECT, because it
      can be applied to conventional SPECT systems without any hardware for TEW
      acquisition and is available for routine clinical use for its simplicity.

PMID- 9183148
TI  - [Measurement of circulating 1,25-dihydroxyvitamin D employing radioimmunoassay].
AB  - Measurement of serum 1,25-dihydroxyvitamin D levels is important for diagnosis of
      various calcium metabolism disorders. Conventional assays for 1,25
      dihydroxyvitamin D employed specific 1,25-dihydroxyvitamin D receptor as binding
      site for the ligand and thus, biologically active 1,25-dihydroxyvitamin D ligand,
      which is labeled with 3H, was required. Usage of 3H made assays cumbersome works.
      A new assay which uses specific antibody as the binding site and the radioligand
      labeled with 125I is now available as a commercial kit. Using these kits, we
      first studied basically the reproducibility, recovery, cross-reactivity and
      comparison with conventional assays. All of those results were satisfactory.
      Secondly, we measured clinically in 111 healthy adults and in patients with
      various disorders such as renal failure, primary hyperparathyroidism,
      hypoparathyroidism and sarcoidosis. This newly available kit for measurement of
      circulating 1,25-dihydroxyvitamin D is proved to be useful in clinical evaluation
      of calcium metabolic disorders.

PMID- 9183150
TI  - [Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment
      model (MPC method) to pediatric patients].
AB  - Measurement of 99mTc-MAG3 plasma clearance based on 1-compartment model (MPC
      method) were applied to 12 pediatric patients and evaluated for the factors which
      might affect the calculated results. Depth correction is a critical factor for
      the measurement of renal uptake. Three different equations for estimating renal
      depth were compared with the real depth measured by ultrasonography. The equation
      proposed by K. Itoh was suitable though the equations by T. Ito and Raynaud were
      insufficient. Estimation of distribution volume, which is regarded as circulating
      plasma volume (CPV), is also critical for the calculation of MAG3 clearance by
      MPC method. Precisely, hematocrit measured by venous sampling and circulating
      blood volume (CBV) calculated as 7.5% of body weight are used for estimation of
      CPV. However, assumed CPV as 5% of body weight was acceptable if the hematocrit
      was not severely deviated from the normal value. Simplified MPC method utilizing
      two factors mentioned above gave a positive correlation with Russell's one point
      sampling method. In conclusion, MPC method is applicable for pediatric patients.

PMID- 9183151
TI  - Long term effect of osteomyelitis.

PMID- 9183152
TI  - Simplified percent body fat predictor.

PMID- 9183153
TI  - Intravenous line diameter: is bigger really better?

PMID- 9183154
TI  - Response to doxycycline vs. mefloquine.

PMID- 9183155
TI  - Anesthesia during a mass-casualty disaster: the Army's experience at Fort Bragg,
      North Carolina, March 23, 1994.

PMID- 9183156
TI  - A survey of outpatient visits in a United States Army forward unit during
      Operation Desert Shield.
AB  - Reports suggest that deployed soldiers during Operations Desert Shield and Desert
      Storm remained healthy, but primary care data are limited. We reviewed the
      outpatient visit surveillance data from the 3d Armored Cavalry Regiment to obtain
      information regarding soldiers' health in the field. Nontraumatic orthopedic
      problems accounted for the highest incidence of primary health care visits,
      followed by unintended injuries, gastrointestinal, respiratory, and dermatologic
      conditions. Visits for heat injuries, sexually transmitted diseases, unexplained
      fever, and psychiatric problems were low, probably due to preventive measures.
      These results suggest that increased prevention to decrease orthopedic problems
      and unintended injuries may substantially reduce outpatient visits during future
      deployments. Medical surveillance during future deployments can be improved by
      taking advantage of current advances in technology to facilitate patient data
      retrieval and provide timely information to first- and second-echelon medical
      personnel.

PMID- 9183157
TI  - Prostatodynia in United Nations peacekeeping forces in Haiti.
AB  - Prostatodynia is a clinical entity associated with voiding symptoms and pelvic
      pain suggestive of prostatitis but with a normal prostate examination and without
      evidence of inflammation or infection in expressed prostatic secretions. The
      problem tends to be chronic and is vexing in its management. Although thought to
      be a common condition, prevalence data are generally lacking. From June to
      October 1995, the U.S. Army's 86th Combat Support Hospital provided medical
      support to a multinational United Nations peacekeeping force in Haiti. Patients
      diagnosed with prostatodynia were more common (13 cases) than men with other
      urologic problems (urolithiasis, 6 cases; urinary tract infection, 6 cases;
      scrotal abscess/mass, 2 cases; epididymitis, 1 case). Patients tended to be young
      (mean age 29.8), had multiple visits, failed to respond to multiple courses of
      antibiotics for presumed "prostatitis," and denied recent sexual relations. Some
      patients reported having had similar symptoms on prolonged separation from their
      spouses in the past that resolved with resumption of normal intercourse.
      Masturbation, however, had no impact on symptoms and was painful in some
      individuals. Terazosin, an alpha-antagonist, and stress-reduction therapy led to
      improvement in some patients' symptoms. A discussion of these retrospective
      findings in light of what is known about the possible etiologies and treatment of
      prostatodynia is presented. Prostatodynia appears to be a common problem in
      deployed troops and can lead to frequent use of medical services. Physicians
      supporting long deployments need to be aware of this entity.

PMID- 9183158
TI  - Military family adaptation to United Nations Operations in Somalia.
AB  - In this first known investigation of family responses to the absence of the
      active duty sponsor deployed to Somalia, 16 adults and 12 children repeatedly
      completed self-report measures of psychopathology and parenting attitudes. Stay
      home parents registered more distress than their deployed spouses. Levels of
      parental intimacy varied significantly over time, reaching its lowest point near
      the end of the mission. Future humanitarian mission deployment support programs
      may need to more effectively address issues of parenting and spousal stress if
      future research confirms our findings.

PMID- 9183159
TI  - Hospital ship doctrine in the United States Navy: the Halsey effect on scoop- and
      sail tactics.
AB  - Although hospital ships have a long history, naval strategists have paid little
      attention to their tactical employment in naval and amphibious warfare. Often
      employed as floating ambulances, operational doctrine for hospital ships did not
      permit their use as floating combat surgical hospitals until the final amphibious
      campaigns of World War II. Based on operational archives-ships' logs, war
      diaries, battle plans, and other official records-this essay traces the evolution
      of tactical doctrine on hospital ships from Guadalcanal to Inchon. Early in World
      War II, there were insufficient hospital ships to permit much flexibility in
      their employment. By the Philippine campaign in 1944, the increased availability
      of afloat medical assets prompted Third Fleet Commander Vice Admiral William F.
      Halsey to propose that the ships be used as acute surgical hospitals at the
      amphibious landing sites rather than as sea-going ambulances. Facing the prospect
      of a growing number of casualties for the major assaults being planned, Halsey
      needed to maximize medical and surgical efficacy and return-to-duty rates to
      conserve the fighting strength of his invasion forces. Admiral Chester A. Nimitz
      approved Halsey's proposal, and the battle plan at Iwo Jima combined the careful
      triage of casualties at the waterfront with early, forward employment of hospital
      ships. Despite more than 21,000 casualties at Iwo Jima, they were handled better
      than at any previous operation in the Pacific theater. The tactical doctrine for
      hospital ships suggested by Halsey has since been employed in every major
      amphibious operation, including Okinawa and Inchon, and has also been used in
      modern-era contingency and humanitarian missions.

PMID- 9183160
TI  - Enteropathogens associated with diarrhea among military personnel during
      Operation Bright Star 96, in Alexandria, Egypt.
AB  - This study investigated the microbial causes of diarrheal disease among U.S.
      troops deployed near Alexandria, Egypt, during October 1995. Bacterial causes
      associated with 19 cases of diarrhea included: enterotoxigenic Escherichia coli
      (ETEC), 42% (21% heat-stable, 11% heat-labile, and 11% heat-stable/ heat-labile
      producers); enteropathogenic E. coli (5.3%); and enteroadherent E. coli (42%).
      Four cases of diarrhea were associated with enteroaggregative E. coli based on
      probe analysis for enteroaggregative heat-stable enterotoxin 1. Protozoan causes
      included; Entamoeba histolytica (11%), E. hartmanni (5%), E. nana (5%),
      Blastocystis hominis (5%), Chilomastix mesnili (11%), Dientamoeba fragilis (5%),
      Entamoeba coli (5%), and Cryptosporidium (5%). Shigella, Aeromonas, Plesiomonas,
      Vibrio, Campylobacter, and Salmonella were not detected. Of the eight ETEC cases,
      one was colonization factor antigen (CFA)/I only, one was both CFA/I and CFA/III,
      three were CFA/II, two were CFA/IV, and two were CFA-negative. Antibiograms of
      the ETEC and enteroadherent E. coli strains showed that all isolates were
      susceptible to norfloxacin, ciprofloxacin, and nalidixic acid but resistant to
      ampicillin, tetracycline, chloramphenicol, and sulfamethoxazole.

PMID- 9183161
TI  - Prevalence of smokeless tobacco use and clinical oral leukoplakia in a military
      population.
AB  - The purpose of this study was to determine the prevalence of smokeless tobacco
      use and clinical leukoplakia in a specific military population. Two hundred
      fourteen soldiers participated in this study. Each participant completed a
      questionnaire-type survey regarding tobacco use and received an annual-type
      dental examination that included extra-oral and intra-oral examination of hard
      and soft tissues and counseling regarding the risks associated with the use of
      tobacco. More than 50% of the participants were between the ages of 18 and 24.
      Survey response indicated that 7.0% used smokeless tobacco, 29.0% smoked
      cigarettes, and 7.9% used both cigarettes and smokeless tobacco. Leukoplakia was
      seen in 4 of the current smokeless tobacco users. Difficulty in cessation was
      experienced by 10 of 32 smokeless tobacco users; 5 continue to use smokeless
      tobacco. Due to the concentration of users in the 18 to 24 age group, efforts
      toward detection and reduction of smokeless tobacco use should be focused on
      junior ranks and younger age groups.

PMID- 9183162
TI  - Sevoflurane concentration available from the universal drawover vaporizer.
AB  - Field anesthesia can have special considerations because of the possibly
      primitive conditions. The drawover vaporizer has enjoyed increased interest
      because of the ability to deliver an anesthetic without electricity or compressed
      gases. Sevoflurane is a potentially attractive field agent because of its
      relative insolubility in blood, giving more rapid control over anesthetic depth.
      We investigated the output of sevoflurane from the drawover vaporizer to
      determine if the concentration is in the necessary range for clinical use. We
      found that the output of the Ohmeda PAC drawover vaporizer delivered between 0.1
      and 3.6% (v/v) sevoflurane. Therefore, the drawover vaporizer should be able to
      deliver a sufficient concentration of sevoflurane for anesthetic maintenance;
      however, this concentration appears inadequate for routine inhalation induction.

PMID- 9183163
TI  - Application of a prognostic scoring system to critically ill patients in a small
      military facility.
AB  - Two hundred one consecutive adult admissions to a 3-bed Special Care Unit in a 25
      bed military hospital were scored using APACHE II (Acute Physiology and Chronic
      Health Evaluation). Outcome measures included APACHE II scores and mortality
      predictions; active intensive care interventions; transfers for specialized care;
      and mortality. Although higher scores generally reflected the need for intensive
      care intervention, admissions with nondiagnostic chest pain had scores that did
      not accurately predict their course. This finding could be explained by bias in
      the original APACHE case mix and by the need for further subclassification of
      cardiovascular disease. APACHE II scoring can be applied in small intensive care
      settings. Scoring criteria and logistic regression equations may need to be
      customized accordingly.

PMID- 9183165
TI  - Oral health problems and treatment needs in Danish military personnel recruited
      for United Nations service.
AB  - A group of 223 men from the Danish Army designated to serve in the United Nations
      forces in the former Yugoslavia were examined to determine their oral health
      status and estimate their needs for dental treatment and the related dental
      treatment time. The population studied consisted of privates (63%),
      noncommissioned officers (28%), and officers (9%). About 80% of the population
      was younger than 28 years. Among the persons older than 27 years, 29% had not
      consulted a dentist within the past 3 years. Subjective symptoms were recorded in
      19% of the study population. The average number of teeth per person was 29.52,
      and none had removable dentures. Only 5 had a decayed-missing and filled surfaces
      value of zero. The officers had almost twice as many untreated dental caries as
      the privates and the noncommissioned officers. The dental fitness of 52%
      permitted immediate service. Among the remaining 48% (N = 107), 2 needed
      extensive treatment and 105 needed some cardiological and/or periodontal
      treatment. The estimated dental treatment time of the population was 185 hours,
      examination time included.

PMID- 9183164
TI  - Vehicle-related fatalities among Swedish conscripts.
AB  - All traffic fatalities among conscripts in Sweden from 1979 through 1988 (N =
      106) were studied. More than half (58%) of the victims were on leave, nearly one
      third (30%) were traveling to or from the regiment, and 13 (12%) were on duty.
      Forty-one percent of the drivers on leave who were involved in crashes were
      inebriated; the mean blood alcohol concentration was 1.6 g/kg. Fifty-two percent
      of the conscripts on leave were injured in single-vehicle crashes. Fatalities
      occurring during travel to or from the regiment most often occurred in crashes
      with another vehicle (69%), and all the drivers were sober. At least one of the
      fatally injured drivers on duty was inebriated, and in another two crashes,
      safety belts were not used although this was compulsory for both passengers and
      drivers. We conclude that collective travel could reduce the danger in traveling
      to and from the regiment. In addition, identifying alcohol abusers and preventing
      them from driving is of prime importance. Increased use of safety belts and
      installation of airbags should also be beneficial as well.

PMID- 9183166
TI  - The extent of military medicine topics taught in military family practice
      residency programs: Part I. A survey of current military family practice
      residency directors.
AB  - The Military Unique Curricula (MUC) was published in 1988 as a guideline for
      instruction at military residencies in military-specific topics. To evaluate the
      degree of implementation and the perceived necessity of the MUC curricula and the
      attitudes and logistical factors relevant to military medicine instruction in
      military family practice residencies, questionnaires were sent to all 18 military
      family practice residency directors. The results reveal a wide range of opinions
      regarding the importance of military medicine and the amount of instruction of
      military medicine topics among the residency programs. The total number of topics
      taught was correlated (p < 0.05) with years as residency director, awareness of
      the MUC, and an opinion that the material would not be better taught at service
      specific schools. There appears to have been little influence of the MUC on the
      curricula of military family practice residencies since its publication.

PMID- 9183167
TI  - The extent of military medicine topics taught in military family practice
      residency programs: Part II, A survey of residency graduates from 1987-1990.
AB  - The Military Unique Curricula (MUC) was published in 1988 as a guideline for
      instruction at military residencies in military-specific topics. Questionnaires
      were sent to 464 military family practice residency graduates from 1987-1990 to
      evaluate the degree of implementation of the MUC and attitudes and logistical
      factors relevant to military medicine instruction in military family practice
      residencies. Analysis reveals a range of opinions regarding the importance of
      military medicine and the amount of instruction on military medicine topics
      offered among programs. The total number of topics offered for instruction was
      positively correlated (p < 0.05) with the time available to teach the material, a
      perception that the material would not be best learned at the Combat Casualty
      Care Course, and the presence of a specific military medicine curriculum within
      the residency. This survey provides baseline information for future evaluation of
      the influence of MUC on military medicine instruction in residency programs.
      Suggestions are offered to improve instruction on military medicine topics in
      military family practice residencies.

PMID- 9183168
TI  - Health profile of Danish army personnel.
AB  - The purpose of the present study was to delineate a health profile of
      professional Danish army personnel. Two-hundred twenty officers, noncommissioned
      officers, and gunners on active duty at Varde Barracks, housing the South Jutland
      Artillery Regiment and the Danish Army Artillery School, were asked about their
      physical and psychological health, interpersonal relations, and working
      conditions as well as their dietary, drinking, and smoking habits. Measurements
      were made of resting pulse rate, blood pressure, height, weight, waist and hip
      girth, and pulmonary function. The ratio of waist-to-hip girth and body mass
      index (BMI) were calculated. Psychological well-being was evaluated using the 12
      item version of the General Health Questionnaire (GHQ). Psychosomatic symptoms
      were frequently reported, but very few of those surveyed appeared to have
      psychiatric disorders as measured by the GHQ. Also, somatic health problems were
      frequently reported, the most frequent being lower-back pain, mild chest pain,
      and sensory disorders. Differences in interpretation and reporting of "lasting
      health problems" may explain the relatively high score for this question. The
      interpersonal relations, both upward and downward in the hierarchy rank order,
      received high scores. Compared with the general population, alcohol consumption
      was very low, whereas smoking-in particular heavy smoking-was much more frequent
      among professional Danish army personnel. Lung function testing showed
      significantly poorer mean values of forced expiratory volume in 1st second of
      expiration and mean forced expiratory flow 25 to 75% of forced vital capacity
      among smokers compared with nonsmokers, although the mean values for the whole
      group of both smokers and nonsmokers were well above reference values for all
      lung function parameters. The frequency of moderately overweight individuals (25
      < BMI < or = 30) was significantly higher among the male army personnel than in
      the general population, whereas this was not the case for obesity (BMI > 30).
      Abdominal obesity, regarded as an independent risk factor for the development of
      ischemic heart disease, stroke, diabetes, hypertension, and all-cause mortality,
      was present in 5%, and 3% belonged to the highest-risk group by having a low BMI
      as well as abdominal obesity.

PMID- 9183169
TI  - Unsuspected abdominal aortic aneurysm.
AB  - This case is an example of an unsuspected abdominal aortic aneurysm. The
      patient's symptoms and the history obtained were suggestive of osteoarthritis.
      The patient sought medical attention for low-back pain through a compensation and
      pension exam.

PMID- 9183170
TI  - Raman on the operating table.

PMID- 9183171
TI  - Linking isocyanates and asthma.

PMID- 9183172
TI  - Reversible oriented surface immobilization of functional proteins on oxide
      surfaces.
AB  - Reversible and oriented immobilization of proteins in a functionally active form
      on solid surfaces is a prerequisite for the investigation of molecular
      interactions by surface-sensitive techniques. We demonstrate a method generally
      applicable for the attachment of proteins to oxide surfaces. A nitrilotriacetic
      acid group serving as a chelator for transition metal ions was covalently bound
      to the surface via silane chemistry. Reversible binding of the green fluorescent
      protein, modified with a hexahistidine extension, was monitored in situ using
      total internal reflection fluorescence. The association constant and kinetic
      parameters of the binding process were determined. The reversible, directed
      immobilization of proteins on surfaces as described here opens new ways for
      structural investigation of proteins and receptor-ligand interactions.

PMID- 9183173
TI  - Complete determination of disulfide forms of purified recombinant human serum
      albumin, secreted by the yeast Pichia pastoris.
AB  - In the case where the supply of material is limited from natural resources and/or
      risks of infection are to be avoided, recombinant proteins are an important
      substitute. Consequently, the physicochemical characterization of the primary and
      tertiary structures of such materials that are to be used clinically is
      indispensable. In this context, disulfide linkages play a significant structural
      role and their determination is of paramount importance. As the demand for human
      serum albumin (HSA), which contains 35 cysteine residues, is continually
      increasing, its industrial-scale production from the genetically engineered yeast
      Pichia pastoris is of interest. The present paper describes a methodology that
      allows the characterization of the multi-disulfide linkages including exact
      positions in purified recombinant HSA by use of gas-phase protein sequencing.
      Mild Edman degradation followed by isocratic analysis of the phenylthiohydantoin
      amino acids in combination with multienzymatic digestions in acidic conditions
      allowed the exact positions of the 17 disulfide bridges and 1 sulfhydryl group to
      be rigorously determined. The sulfhydryl content of the present recombinant HSA
      was the same as plasma HSA.

PMID- 9183174
TI  - Determination of paclitaxel and related taxanes in bulk drug and injectable
      dosage forms by reversed phase liquid chromatography.
AB  - Baseline separation of 15 taxanes including paclitaxel (Taxol) was achieved on
      pentafluorophenyl (PFP) HPLC columns. Methods using aqueous acetonitrile
      gradients on each of two commercial PFP columns were developed that are suitable
      for the determination of potency, content uniformity, and degradation profile of
      the paclitaxel bulk drug and injectable dosage form. The elution order is
      apparently related to molecular size, the number of acetylated hydroxyl groups,
      and the substitution of a xylosyl group at the 7-position. The resolution of
      several of the taxanes is a sensitive function of the starting eluent composition
      and the programming rate, which requires optimization of the methods on both
      columns. Retention of 10 of the taxanes was studied over the temperature range
      from 30 to 70 degrees C, and enthalpies of transfer, delta H degree, were
      determined. Conversion of a hydroxy group to an acetyl group, which can interact
      more strongly with the fluorines on the PFP, has a large effect on the delta H
      degree, as does the addition of a xylosyl derivative to the 7-hydroxy. The
      methods developed for the injectable drug form allow good resolution of the
      taxanes from the excipient Cremophor EL, a polyethoxylated castor oil used with
      ethanol to solubilize the paclitaxel. The methods for the bulk drug were fully
      validated in terms of accuracy, precision, specificity including forced
      degradation, limits of detection and quantitation, and linearity and range.

PMID- 9183175
TI  - Amperometric immunosensors based on rigid conducting immunocomposites.
AB  - Novel polishable immunosensors based on rigid biocomposite materials have been
      constructed. These biocomposites contain graphite powder, rabbit IgG, and
      methacrylate or epoxy resins. This material acts as a reservoir for the
      biological molecules and as a transducer at the same time. In order to study the
      potential analytical properties of this new type of material, a competitive
      binding assay was developed to determine the RIgG present in a sample with the
      aid of goat anti-rabbit IgG labeled with alkaline phosphatase. Using phenyl
      phosphate as a substrate, the phenol produced by the enzymatic reaction was
      amperometrically detected at 800 mV (vs Ag/AgC1). The surface of the immunosensor
      can be regenerated by simply polishing, obtaining fresh immunocomposite ready to
      be used in a new competitive assay.

PMID- 9183176
TI  - Modified pulsed-field gradient NMR experiments for improved selectivity in the
      measurement of diffusion coefficients in complex mixtures: application to the
      analysis of the Suwannee River fulvic acid.
AB  - To simplify the complex 1H NMR spectrum of a fulvic acid sample and gain
      structural and molecular size information, spectral editing techniques were used
      in conjunction with a general PFG NMR pulse sequence. These editing techniques
      exploit differences in T1 and T2 relaxation times as well as differences in
      coupling constants. The experiments were initially performed on a model mixture
      of glutamic acid and ethyl acetate in order to validate the method as a technique
      for measurement of diffusion coefficients. The editing experiments were then
      applied to the International Humic Substances Society Suwannee River fulvic acid
      standard. These editing techniques allowed more selective measurement of
      diffusion coefficients for broad classes of components within regions of the 1H
      NMR spectrum of the fulvic acid solution. The average radii of gyration
      calculated for the Suwannee River fulvic acid sample from the diffusion
      coefficients are in good agreement with literature values.

PMID- 9183177
TI  - Simultaneous solid phase extraction, derivatization, and gas chromatographic mass
      spectrometric quantification of thromboxane and prostacyclin metabolites,
      prostaglandins, and isoprostanes in urine.
AB  - The current analytical methods for the various prostanoids require a separate and
      extended sample workup, derivatization, and gas chromatographic/mass
      spectrometric detection of each compound. Therefore, we developed and validated a
      rapid method for the common purification, derivatization, and GC/MS determination
      of 11-dehydrothromboxane B2, 2,3-dinor-6-keto-PGF1a, PGF2A, PGE2, PGD2, and
      isoprostanes in urine. A single reversed-phase solid-phase extraction step and
      modified reaction conditions yielded excellent sample purification at high
      recoveries and efficient derivatization for all compounds in one vial. The method
      allows, for the first time, the simultaneous quantification of these index
      metabolites of systemic thromboxane and prostacyclin synthesis, renal
      prostaglandin formation, and nonenzymatic in vivo lipid peroxidation in a single
      GC/MS run with high sensitivity and precision.

PMID- 9183178
TI  - Functional wave time-lag focusing matrix-assisted laser desorption/ionization in
      a linear time-of-flight mass spectrometer: improved mass accuracy.
AB  - A strength of matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry is its ability to analyze mixtures without separation. MALDI mass
      spectrometers capable of providing a linear mass calibration over a broad mass
      range should find wide use in these applications. This work addresses issues
      pertinent to mass measurement accuracy of a time-lag focusing MALDI time-of
      flight instrument and presents a new approach to improving mass accuracy by using
      a functional wave extraction pulse, instead of a square wave, for time-lag
      focusing. A model is described of an ideal extraction pulse shape that provides
      constant total kinetic energy for all ions. If total kinetic energy is constant,
      then there is an exact linear correlation between ion mass and flight time raised
      to the second power. Using a descending wave extraction pulse, it is demonstrated
      that mass accuracy of better than 30 ppm using two internal calibrants and better
      than 70 ppm using external calibrants can be obtained over a 25 ku mass range.
      The practical aspects of an instrument needed to obtain consistent mass accuracy
      is discussed. It is found that ion flight time shows a small dependence upon
      laser flux; flight times increase slightly as the flux increases. But this
      dependence is much smaller than is observed in continuous-extraction MALDI.

PMID- 9183179
TI  - Pulsed ultrafiltration mass spectrometry: a new method for screening
      combinatorial libraries.
AB  - In response to the need for rapid screening of combinatorial libraries to
      identify new lead compounds during drug discovery, we have developed an on-line
      combination of ultrafiltration and electrospray mass spectrometry, called pulsed
      ultrafiltration mass spectrometry, which facilitates the identification of
      solution-phase ligands in library mixtures that bind to solution-phase receptors.
      After ligands contained in a library mixture were bound to a macromolecular
      receptor, e.g., human serum albumin or calf intestine adenosine deaminase, the
      ligand-receptor complexes were purified by ultrafiltration and then dissociated
      using methanol to elute the ligands into the electrospray mass spectrometer for
      detection. Ligands with dissociation constants in the micromolar to nanomolar
      range were successfully bound, released, and detected using this method,
      including warfarin, salicylate, furosemide, and thyroxine binding to human serum
      albumin, and erythro-9-(2-hydroxy-3-nonyl)adenine binding to calf intestine
      adenosine deaminase. Repetitive bind- and-release experiments demonstrated that
      the receptor could be reused. Thus, pulsed ultrafiltration mass spectrometry was
      shown to provide a simple and powerful new method for the screening of
      combinatorial libraries in support of new drug discovery.

PMID- 9183180
TI  - Representing primary electrophoretic data in the 1/time domain: comparison to
      representations in the time domain.
AB  - A plot of absorbance vs 1/time (the "1/time domain") is a more useful
      representation of the primary data in capillary electrophoresis than traditional
      plots of absorbance vs time (the "time domain") in a wide set of circumstances,
      especially when comparing electropherograms in which the rate of electroosmotic
      flow is not precisely the same. The quantity that is of fundamental interest in
      capillary electrophoresis (CE) is the electrophoretic mobility of an analyte. The
      electrophoretic mobility of a species is nonlinearly proportional to time and,
      therefore, not linearly represented in the time domain: that is, the distance
      between two peaks along the time axis is not linearly related to the difference
      in their electrophoretic mobilities. In contrast, the electrophoretic mobility is
      linearly proportional to 1/time, and the distance between two peaks along the
      1/time axis is linearly related to the difference in electrophoretic mobilities.
      Plots in the 1/time domain are similar to the familiar plots in the time domain
      (each analyte is represented by a peak, and the order of peaks corresponds to the
      order in which these analytes reach the detector), but the spacing between the
      peaks corresponds linearly to differences in mobility. This article derives this
      useful, visually appealing, and broadly applicable plotting strategy and
      illustrates common situations in which these plots are more useful than plots in
      the time domain.

PMID- 9183181
TI  - High-speed DNA genotyping using microfabricated capillary array electrophoresis
      chips.
AB  - Capillary array electrophoresis (CAE) chips have been designed and fabricated
      with the capacity to rapidly (< 160 s) analyze 12 different samples in parallel.
      Detection of all lanes with 0.3 s temporal resolution was achieved using a laser
      excited confocal-fluorescence scanner. The operation and capabilities of these
      CAE microdevices were first determined by performing electrophoretic separations
      of pBR322 MspI DNA samples. Genotyping of HLA-H, a candidate gene for the
      diagnosis of hereditary hemochromatosis, was then performed to demonstrate the
      rapid analysis of biologically relevant samples. Two-color multiplex fluorescence
      detection of HLA-H genotypes was accomplished by prelabeling the standard pBR322
      MspI DNA ladder with a red emitting bis-intercalation dye (butyl TOTIN) and on
      column labeling of the HLA-H DNA with thiazole orange. This work establishes the
      feasibility of using CAE chips for high speed, high-throughput genotyping.

PMID- 9183182
TI  - A study of the efficiency of polybutadiene-coated zirconia as a reversed-phase
      chromatographic support.
AB  - This work describes the dynamic characteristics of columns packed with
      polybutadiene (PBD)-coated zirconia. Reduced plate height (h) vs reduced velocity
      (v) data for alkylbenzenes were acquired for three phases coated with different
      amounts of PBD. Additional data for benzene (k' = 0) on uncoated and four coated
      phases were also collected. These h vs v plots have a minimum between 4 and 5,
      indicating good but not excellent column efficiency. By fitting the Knox equation
      to these data, the A (packing quality), B (axial diffusion), and C (mass transfer
      resistance) coefficients were determined. The A coefficients were about 2 in all
      cases, and the B coefficients had values between 2 and 3. The C coefficients
      varied from 0.05 to 0.2, depending on the polymer load. The data suggest that the
      quality of packing and the efficiency of mass transfer resistance in the "film"
      of polymeric stationary phase, not the stagnant mobile phase, are key to further
      improvements in column performance. The amount of polymer loaded significantly
      affects the efficiency through the mass transfer resistance in the stationary
      phase.

PMID- 9183183
TI  - Evaluation of temperature effects on selectivity in RPLC separations using
      polybutadiene-coated zirconia.
AB  - The effect of temperature on selectivity in RPLC method development has been
      evaluated on polybutadiene-coated zirconia. We find that the influence of
      temperature on selectivity depends strongly on solute type. For solutes of
      similar structure such as polyaromatic hydrocarbons, temperature has almost no
      effect on selectivity; however, for solutes with very different functional groups
      such as chlorophenols, temperature changes did significantly affect selectivity.
      We feel that simple mixtures with one dominant retention mechanism-e.g.,
      solvophobic retention-will not be helped appreciably by adjusting temperature.
      However, in complex mixtures with polar and ionizable solutes, optimization by
      varying the temperature may well be fruitful.

PMID- 9183184
TI  - Fast temporal response fiber-optic chemical sensors based on the photodeposition
      of micrometer-scale polymer arrays.
AB  - Fiber-optic chemical sensor microarrays for the detection of pH and O2 have been
      developed with subsecond response times. Sensor microarrays are fabricated by the
      covalent immobilization (pH sensor arrays) or the physical entrapment (O2 sensor
      arrays) of fluorescent indicators in photodeposited polymer matrices on optical
      imaging fibers. Polymer microarrays are comprised of thousands of individual
      elements photodeposited as hemispheres such that each element of the sensor array
      is coupled directly to a discrete optical element of the imaging fiber and is not
      in contact with other neighboring elements. Because of the hemispherical shape
      and the individuality of the array elements, diffusion of analyte to the sensor
      elements is dominated by radial diffusion, resulting in a rapid response time. pH
      sensitive arrays based on fluorescein respond to a 1.5-unit pH change within 300
      ms, while the O2-sensitive arrays respond to O2 changes within 200 ms (90% of
      steady state response).

PMID- 9183185
TI  - Simultaneous separation of soya bean and animal whey proteins by reversed-phase
      high-performance liquid chromatography. Quantitative analysis in edible samples.
AB  - A reversed-phase high-performance liquid chromatography method was developed
      successfully for the simultaneous and rapid separation of the main soya bean
      proteins (globulins) and animal whey proteins (alpha-lactalbumin and beta
      lactoglobulin). This method consisted of a linear gradient of two mobile phases
      (0.1% trifluoroacetic acid in water and 0.1% trifluoroacetic acid in
      acetonitrile). For the first time, soya bean globulins were separated from animal
      whey proteins. The analysis time for this separation was 20 min, eluting soya
      bean globulins in the first 10 min. The method was applied to quantify soya bean
      proteins in soya bean commercial milks with the possibility of detecting the
      presence of animal whey proteins. Adulteration of a powdered soya bean milk by
      animal whey proteins was detected. The possibility of detecting the presence of
      soya bean proteins in animal milks was also studied.

PMID- 9183186
TI  - The future of healthcare systems.

PMID- 9183187
TI  - Managing diabetes after myocardial infarction.

PMID- 9183188
TI  - At last, a public health minister.

PMID- 9183189
TI  - Requesting necropsies.

PMID- 9183190
TI  - Meet Minerva in cyberspace.

PMID- 9183191
TI  - Cardiologist admits research misconduct.

PMID- 9183192
TI  - Britain declares war on smoking.

PMID- 9183193
TI  - Learning to break bad news.

PMID- 9183194
TI  - Woman dies two months after food withdrawal.

PMID- 9183195
TI  - Invasive devices increase risk of infection.

PMID- 9183196
TI  - US senate likely to ban controversial abortion procedure.

PMID- 9183198
TI  - India protects jobs of people with HIV infection.

PMID- 9183197
TI  - High amounts of chemicals found in breast milk.

PMID- 9183199
TI  - Romania plans tough antismoking laws.

PMID- 9183200
TI  - Eye disease associated with handling pet tarantulas: three case reports.

PMID- 9183201
TI  - Are antibiotics indicated as initial treatment for children with acute otitis
      media? A meta-analysis.
AB  - OBJECTIVE: To determine the effect of antibiotic treatment for acute otitis media
      in children. DESIGN: Systematic search of the medical literature to identify
      studies that used antibiotics in randomised controlled trials to treat acute
      otitis media. Studies were examined blind, and the results of those of
      satisfactory quality of methodology were pooled. SUBJECTS: Six studies of
      children aged 7 months to 15 years. MAIN OUTCOME MEASURES: Pain, deafness, and
      other symptoms related to acute otitis media or antibiotic treatment. RESULTS:
      60% of placebo treated children were pain free within 24 hours of presentation,
      and antibiotics did not influence this. However, at 2-7 days after presentation,
      by which time only 14% of children in control groups still had pain, early use of
      antibiotics reduced the risk of pain by 41% (95% confidence interval 14% to 60%).
      Antibiotics reduced contralateral acute otitis media by 43% (9% to 64%). They
      seemed to have no influence on subsequent attacks of otitis media or deafness at
      one month, although there was a trend for improvement of deafness at three
      months. Antibiotics were associated with a near doubling of the risk of vomiting,
      diarrhoea, or rashes (odds ratio 1.97 (1.19 to 3.25)). CONCLUSIONS: Early use of
      antibiotics provides only modest benefit for acute otitis media: to prevent one
      child from experiencing pain by 2-7 days after presentation, 17 children must be
      treated with antibiotics early.

PMID- 9183202
TI  - Population based study of use of anticoagulants among patients with atrial
      fibrillation in the community.

PMID- 9183204
TI  - ABC of mental health. Mental health assessment.

PMID- 9183203
TI  - Treating acute pain in hospital.

PMID- 9183205
TI  - The performance of doctors. I: Professionalism and self regulation in a changing
      world.

PMID- 9183206
TI  - Health in China. From Mao to market reform.
AB  - After the Liberation by Mao Ze Dong's Communist army in 1949, China experienced
      massive social and economic change. The dramatic reductions in mortality and
      morbidity of the next two decades were brought about through improvements in
      socioeconomic conditions, an emphasis on prevention, and almost universal access
      to basic health care. The economic mismanagement of the Great Leap Forward
      brought about a temporary reversal in these positive trends. During the Cultural
      Revolution there was a sustained attack on the privileged position of the medical
      profession. Most city doctors were sent to work in the countryside, where they
      trained over a million barefoot doctors. Deng Xiao Ping's radical economic
      reforms of the late 1970s replaced the socialist system with a market economy.
      Although average incomes have increased, the gap between rich and poor has
      widened.

PMID- 9183207
TI  - Socioeconomic determinants of health. The contribution of nutrition to
      inequalities in health.
AB  - Social class differences in health are seen at all ages, with lower socioeconomic
      groups having greater incidence of premature and low birthweight babies, heart
      disease, stroke, and some cancers in adults. Risk factors including lack of
      breast feeding, smoking, physical inactivity, obesity, hypertension, and poor
      diet are clustered in the lower socioeconomic groups. The diet of the lower
      socioeconomic groups provides cheap energy from foods such as meat products, full
      cream milk, fats, sugars, preserves, potatoes, and cereals but has little intake
      of vegetables, fruit, and wholewheat bread. This type of diet is lower in
      essential nutrients such as calcium, iron, magnesium, folate, and vitamin C than
      that of the higher socioeconomic groups. New nutritional knowledge on the
      protective role of antioxidants and other dietary factors suggests that there is
      scope for enormous health gain if a diet rich in vegetables, fruit, unrefined
      cereal, fish, and small quantities of quality vegetable oils could be more
      accessible to poor people.

PMID- 9183208
TI  - Diagnosing pulmonary embolism. Three non-invasive techniques failed to get a
      mention.

PMID- 9183209
TI  - Diagnosing pulmonary embolism. Not all procedures are invasive.

PMID- 9183210
TI  - Diagnosing pulmonary embolism. Lung perfusion scanning is a useful diagnostic
      tool.

PMID- 9183211
TI  - Diagnosing pulmonary embolism. Outcome depends on size of embolus.

PMID- 9183212
TI  - Diagnosing pulmonary embolism. Morbidity should be taken into account when
      deciding on anticoagulant treatment.

PMID- 9183213
TI  - Intravenous antibiotic treatment at home can provide higher quality care.

PMID- 9183214
TI  - Macrocytic anaemias. Three fifths of patients with Crohn's disease that has not
      been operated on have vitamin B12 malabsorption.

PMID- 9183215
TI  - Pancreatic angiography is still valuable preoperatively in insulinoma.

PMID- 9183216
TI  - Public is concerned about gene testing.

PMID- 9183217
TI  - Leukaemia near La Hague nuclear plant. Bias could have been introduced into
      study.

PMID- 9183218
TI  - Leukaemia near La Hague nuclear plant. Study design is questionable.

PMID- 9183219
TI  - Leukaemia near La Hague nuclear plant. Scientific context is needed.

PMID- 9183220
TI  - Leukaemia near La Hague nuclear plant. Case-control studies have been done in
      Britain.

PMID- 9183221
TI  - Leukaemia near La Hague nuclear plant. Deformed insects have been found near
      nuclear plants.

PMID- 9183222
TI  - Advertisements for donepezil (Aricept) in the BMJ. Advertisement suggests an
      unrealistic improvement in mental status.

PMID- 9183224
TI  - Nurses are right not to take on responsibilities for which they have not been
      properly prepared.

PMID- 9183223
TI  - Advertisements for donepezil (Aricept) in the BMJ. Local committee has declined
      to approve NHS hospital prescription of donepezil.

PMID- 9183225
TI  - Should we measure lipoprotein Lp(a)?

PMID- 9183226
TI  - Postherpetic neuralgia. Predicting and preventing risk.

PMID- 9183227
TI  - Lipoprotein Lp(a) excess and coronary heart disease.
AB  - Lipoprotein Lp(a) excess has been identified as a powerful predictor of premature
      atherosclerotic vascular disease in several large, prospective studies.
      Lipoprotein Lp(a) levels modulate the risk of coronary heart disease in patients
      with hypercholesterolemia, and lipoprotein Lp(a) excess is commonly detected in
      men and women with premature coronary atherosclerosis. Lipoprotein Lp(a)
      contributes to atherothrombotic risk by multiple mechanisms that include impaired
      fibrinolysis, increased cholesterol deposition in the arterial wall, and enhanced
      oxidation of low density lipoprotein cholesterol. Although low density
      lipoprotein cholesterol reduction is the primary intervention in patients with
      lipoprotein Lp(a) excess, specific therapy to lower lipoprotein Lp(a) may be
      indicated for patients with premature coronary atherosclerosis, a strong family
      history of premature atherosclerosis, or refractory hypercholesterolemia. In
      consideration of the high prevalence of lipoprotein Lp(a) excess in patients with
      premature coronary heart disease and the intricate role of lipoprotein Lp(a) in
      atherothrombosis, this review provides an evidence-based approach to the
      screening and treatment of patients with lipoprotein Lp(a) excess.

PMID- 9183228
TI  - Cholesterol and coronary heart disease. The 21st century.
AB  - Recent clinical trials have demonstrated that reductions of serum low-density
      lipoprotein (LDL) levels substantially decrease the risk for coronary heart
      disease. These trials confirm other lines of evidence that high levels of LDL are
      a critical atherogenic factor. Aggressive lowering of LDL levels in high-risk
      patients promises to significantly reduce morbidity and mortality from coronary
      heart disease in the first third of the 21st century. However, several additional
      measures will be required to marginalize coronary heart disease in the 21st
      century. Other lipoprotein abnormalities and other risk factors, eg, cigarette
      smoking, hypertension, and diabetes mellitus, must be controlled to obtain the
      full benefit of LDL-lowering therapy. Moreover, the health care delivery system
      must be reorganized to put more emphasis on prevention. Although much can be
      achieved through application of current knowledge in prevention efforts, further
      advances through new research will be required to remove coronary heart disease
      as a major cause of death in the United States.

PMID- 9183229
TI  - A comparison of estrogen replacement, pravastatin, and combined treatment for the
      management of hypercholesterolemia in postmenopausal women.
AB  - OBJECTIVES: To evaluate and compare the lipid-altering effects of conjugated
      estrogens and pravastatin, alone and in combination, in postmenopausal women with
      hypercholesterolemia. METHODS: This was a double-blind, randomized, placebo
      controlled clinical trial with 4 parallel groups. Participants (N = 76) were
      randomly assigned to receive conjugated estrogens, 0.625 mg/d; pravastatin
      sodium, 20 mg/d; conjugated estrogens plus pravastatin; or a placebo for 16
      weeks. RESULTS: Primary end points were changes in serum lipid parameters. Among
      participants treated with conjugated estrogens, levels of non-high density
      lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density
      lipoprotein cholesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%)
      and triglycerides (4.2%) increased. Participants in the pravastatin group
      achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels,
      respectively. Levels of HDL-C increased slightly (3.7%) and triglycerides
      decreased by 12.1%. Among participants treated with a combination of conjugated
      estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%)
      responses were similar to those of the pravastatin group, and the HDL-C response
      (21.2%) was similar to that observed in the conjugated estrogens group.
      Triglyceride levels remained similar to baseline (-0.9%) in the combined
      treatment group. CONCLUSIONS: Administration of conjugated estrogens resulted in
      potentially antiatherogenic changes in levels of non-HDL-C, HDL-C, and calculated
      LDL-C. The HDL-C response to combined treatment was similar to that observed in
      women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses
      to combined treatment were similar to those produced by pravastatin therapy
      alone. These findings support the position of the National Cholesterol Education
      Program that estrogen replacement, with a progestin where indicated, should be
      given consideration as a therapeutic option for the management of
      hypercholesterolemia in postmenopausal women.

PMID- 9183230
TI  - Guidelines and realities of asthma management. The Philadelphia story.
AB  - BACKGROUND: Guidelines from the National Heart, Lung, and Blood Institute,
      Bethesda, Md, have encouraged more frequent use of inhaled steroids in asthma
      management. OBJECTIVES: To determine (1) whether prescription rates for inhaled
      steroids have increased compared with prescriptions for bronchodilators and (2)
      significant associations of demographic factors with bronchodilator-inhaled
      steroid prescription ratios and with rates of inhaled steroid prescriptions.
      DESIGN: Cross-sectional analysis of monthly bronchodilator and inhaled steroid
      prescription rates, numbers and types of asthma care providers, and demographic
      factors. SETTING: Philadelphia, Pa. MEASUREMENTS: Using univariate and
      multivariate analyses, bronchodilator and inhaled steroid prescription rates were
      determined for 45 ZIP codes and studied for associations with race and ethnicity,
      poverty, educational attainment, marital status, gender, total numbers of asthma
      drug prescriptions, and numbers and types of asthma care providers. RESULTS:
      Monthly bronchodilator-inhaled steroid prescription ratios increased from July
      1991 to June 1993 (P < .001). Prescription rates for inhaled steroids and inhaled
      bronchodilators declined, but rates for oral bronchodilators (beta-agonists and
      theophylline) increased. By stepwise multiple regression, higher bronchodilator
      inhaled steroid prescription ratios and lower inhaled steroid prescription rates
      were each significantly associated with ZIP codes in which greater proportions of
      residents lacked a high school diploma (P < .001); associations that approached
      statistical significance were found for higher bronchodilator-inhaled steroid
      ratios and fewer asthma care providers (P = .05) and for lower inhaled steroid
      prescription rates and lower proportions of asthma specialists (P = .04).
      CONCLUSIONS: In Philadelphia, a gap exists between optimal asthma drug
      prescribing and actual prescribing patterns that has widened from July 1991 to
      June 1993. Underuse of inhaled steroids is most closely associated with lower
      educational attainment, suggesting that interventions that include addressing the
      special asthma care needs of a low-literacy population will be required to
      achieve the goals of the National Asthma Education Program.

PMID- 9183231
TI  - Specialty differences in the management of asthma. A cross-sectional assessment
      of allergists' patients and generalists' patients in a large HMO.
AB  - OBJECTIVE: To examine the differences in medical management and quality of life
      between patients with asthma who receive their primary asthma care from
      allergists and those who receive their care from generalists in a large health
      maintenance organization (HMO). METHODS: We conducted a cross-sectional study of
      patients with asthma in a large HMO (Kaiser Permanente, Northwest Region,
      Portland, Ore). Participants were 392 individuals aged 15 through 55 years with
      physician-diagnosed asthma, taking antiasthma medications, reporting current
      asthma symptoms, and receiving asthma care from an allergist or from a
      generalist. Primary outcomes include characteristics of asthma, health care
      utilization, and quality of life. RESULTS: Patients cared for by allergists
      tended to have more severe asthma than those cared for by generalists (P < .01).
      The allergists' patients tended to be older (38.6 +/- 9.6 years vs 35.7 +/- 12.6
      years, P < .01), more atopic (91% vs 78%, P < .01), and more likely to report
      perennial (rather than seasonal) asthma (26% vs 36%, P < .04) than the
      generalists' patients. Patients receiving their primary asthma care from an
      allergist were considerably more likely than generalists' patients to report
      using inhaled anti-inflammatory agents (P < .01), oral steroids (P < .01), and
      regular (daily) breathing medications to control their asthma (P < .01).
      Allergists' patients were more likely to have asthma exacerbations treated in a
      clinic setting rather than an emergency department (P < .01). Furthermore,
      allergists' patients reported significantly improved quality of life as measured
      by several dimensions of the SF-36 scale (physical functioning, role emotional,
      bodily pain, and general health; P < .05). CONCLUSIONS: These findings suggest
      that specialist care of asthma is of benefit for patients with asthma in a large
      HMO. Specifically, the allergists' patients conformed more closely to national
      asthma management guidelines and reported better quality of life than did the
      generalists' patients.

PMID- 9183232
TI  - The sequelae of herpes zoster.
AB  - BACKGROUND: The last 40 years was a period during which the incidence of herpes
      zoster appears to have increased substantially. OBJECTIVE: To determine whether
      the risk of complications of herpes zoster has changed during the last 40 years.
      METHODS: The automated medical records of a health maintenance organization were
      screened for diagnosis codes suggesting herpes zoster and potentially complicated
      cases of zoster. The predictive value of a herpes zoster diagnosis was calculated
      from sampling full-text records. Records of all patients with codes suggesting
      complications were reviewed in full. RESULTS: Of 859 individuals with herpes
      zoster who met the eligibility criteria, 101 were identified who experienced at
      least 1 complication, corresponding to a 60-day risk of 12%. Corrected for the
      sensitivity of the complication-finding strategy, the risk estimate was 14%. Risk
      increased markedly with age, with those older than 64 years having more than 6
      times the risk of complications of those younger than 25 years (odds ratio, 8.3;
      95% confidence interval, 2.5-29.3). Trigeminal distribution of rash and the
      presence of certain conditions associated with immune compromise appeared to
      increase risk. CONCLUSIONS: The apparent increase in the incidence of herpes
      zoster was not accompanied by a change in the risk of specific or overall
      complications in a population-based sample. Advanced age and other conditions
      associated with waning cellular immunity may confer an increased risk of
      experiencing a complicated course of herpes zoster.

PMID- 9183233
TI  - Risk factors for postherpetic neuralgia.
AB  - BACKGROUND: The risk factors for postherpetic neuralgia (PHN), the most common
      complication of herpes zoster, have not been well established. OBJECTIVE: To
      elucidate the risk factors for PHN. METHODS: Automated medical, claims, and
      pharmacy records of a health maintenance organization were used to identify cases
      of PHN and obtain data on risk factors. A case-base design was used to assess the
      impact of various patient, disease, and treatment factors on the prevalence of
      PHN 1 and 2 months after developing zoster. RESULTS: There were 821 cases of
      herpes zoster that met all eligibility criteria. The prevalence of PHN more than
      30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%)
      and 4.5% (95% CI, 3.2%-6.2%) after 60 days. Compared with patients younger than
      50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence
      (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4)
      60 days after developing zoster. Prodromal sensory symptoms and certain
      conditions associated with compromised immunity were also associated with PHN.
      Systemic corticosteroids before zoster and treatment of zoster with acyclovir or
      corticosteroids did not significantly affect the prevalence of PHN. CONCLUSIONS:
      Increased age and prodromal symptoms are associated with higher prevalence of PHN
      1 and 2 months after onset of zoster. Overall, systemic acyclovir appears not to
      confer any protection against PHN, although benefit among elderly patients cannot
      be excluded.

PMID- 9183234
TI  - The place of renal scintigraphy in the diagnosis of renal artery stenosis.
      Fifteen years of clinical experience.
AB  - BACKGROUND: Renal scintigraphy with radiolabeled pentetic acid
      (diethylenetriamine pentaacetic acid [DTPA]) or, more recently, mertiatide
      (mercaptoacetyltriglycine [MAG3]), with or without captopril challenge, is widely
      recommended as a diagnostic test for renal artery stenosis. OBJECTIVES: To
      address (1) whether the diagnostic accuracy has been improved by the use of
      captopril and the introduction of mertiatide and (2) whether a renal scan that
      shows abnormalities is a useful criterion to select patients for renal
      arteriography. PATIENTS AND METHODS: A standard diagnostic protocol, using both
      scintigraphy and arteriography, was followed in 505 consecutive high-risk
      hypertensive patients who were evaluated for renovascular hypertension at the
      University Hospital Dijkzigt, Rotterdam, the Netherlands, from 1978 to 1992.
      RESULTS: Renal artery stenosis (> or = 50%) was present in 263 patients. When the
      single-kidney fractional uptake was used as a diagnostic criterion, a specificity
      of 0.90 was obtained at a cutoff value of 35% for the worst kidney in
      scintigraphy using pentetic acid without captopril challenge (n = 225) and at a
      cutoff value of 37% after captopril challenge (n = 280). This was associated with
      sensitivity levels of 0.65 and 0.68, respectively. The difference between the
      uptake of pentetic acid with and without captopril challenge in the 85 patients
      who were studied under both circumstances was no more accurate as a predictor of
      renal artery stenosis. In the 93 patients who were studied with mertiatide as
      well as with pentetic acid, both after captopril challenge, the diagnostic
      accuracy was no better with mertiatide than with pentetic acid; mertiatide failed
      to offer any advantage not only when the single-kidney fractional uptake was used
      as a criterion, but also with the use of other scintigraphic parameters (eg, time
      to peak, time to pyelum, overall shape of renographic curve, and kidney size).
      CONCLUSIONS: The diagnostic accuracy of renal scintigraphy has not been improved
      by the introduction of mertiatide or by the use of captopril. The usefulness of
      scintigraphy as a diagnostic test for the presence of renal artery stenosis
      remains questionable. The physician will always confront either a substantial
      number of arteriograms that do not show abnormalities when renal scintigraphy is
      omitted as a screening step or a substantial number of missed diagnoses when a
      renal scan that shows abnormalities is used as a prerequisite for arteriography.

PMID- 9183235
TI  - The efficacy of aspirin in patients with atrial fibrillation. Analysis of pooled
      data from 3 randomized trials. The Atrial Fibrillation Investigators.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of
      stroke. Six randomized studies of the use of oral anticoagulation therapy have
      demonstrated that the relative risk of stroke is decreased by approximately 68%.
      Three of these studies also compared aspirin with placebo use in a double-blind
      design. We pooled individual patient data from these 3 studies. OBJECTIVES: To
      determine if there were subgroups of patients who were particularly responsive to
      aspirin use and to determine the efficacy of aspirin compared with placebo use in
      the broad spectrum of patients with AF. METHODS: There were 1985 patient-years
      assigned to the aspirin and 1867 patient-years assigned to the placebo groups in
      the analysis. The daily dose of aspirin was 75 mg in the Atrial Fibrillation,
      Aspirin, Anticoagulation Study, 325 mg in the Stroke Prevention in Atrial
      Fibrillation 1 Study, and 300 mg in the European Atrial Fibrillation Trial. The
      European Atrial Fibrillation Trial was a secondary prevention trial, while the
      other 2 were primary prevention studies. The primary end point in this analysis
      was ischemic stroke. RESULTS: At the time of randomization, the patients' mean
      age was 70 years and the mean blood pressure was 145/83 mm Hg. Sixty-two percent
      of patients were male, 46% had a history of hypertension, 35% had a previous
      transient ischemic attack or stroke, and 19% had intermittent AF. Although
      aspirin use seemed particularly effective in younger patients and in those with
      hypertension in the Stroke Prevention in Atrial Fibrillation 1 Study, this was
      not the case in the other studies. No other subgroups particularly responsive to
      aspirin therapy were identified. When patients from all the studies were
      combined, the relative risk reduction with aspirin therapy was 21% (95%
      confidence interval, 0%-38%; P = .05). CONCLUSIONS: A subgroup of patients with
      AF that has a particularly large reduction in stroke incidence from aspirin
      therapy was not convincingly identified. The data from the combined analysis of
      these 3 randomized trials suggest a small effect of aspirin use in preventing
      stroke in patients with AF.

PMID- 9183236
TI  - Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic
      bone mineral density.
AB  - BACKGROUND: The level of urinary, type I collagen, crosslinked N-telopeptides
      (NTX) is a new marker of bone resorption. To our knowledge, no population-based
      studies of older adults have determined whether this measure can identify
      individuals with osteoporosis. OBJECTIVES: To measure the levels of NTX in a
      cross-sectional study of ambulatory, older, white adults and to evaluate whether
      this measure of bone resorption could identify individuals with osteoporosis.
      PATIENTS AND METHODS: The subjects, aged 50 to 98 years, formed 3 groups: 374
      men, 223 women currently using estrogen, and 364 women not currently using
      estrogen. A standard medical history and validated record of medication use were
      obtained. Height and weight were measured. Bone mineral density (BMD) was
      measured at the hip and lumbar spine using dual energy x-ray absorptiometry. The
      levels of NTX were measured by enzyme-linked immunosorbent assay. RESULTS:
      Overall, the levels of NTX increased slightly with age in men and in estrogen
      users and more dramatically in nonestrogen users. In a model adjusted for all
      major risk factors for osteoporosis, there was a significant decrease in BMD
      levels by increasing quintiles of NTX levels at the hip and spine in women with
      and without estrogen use and at the hip in men. Using sex-specific, peak bone
      mass criteria and age-adjusted analyses, the levels of NTX discriminated between
      normal (< or = -1.0 SD), osteopenic (> -1.0 and < -2.5 SD), and osteoporotic (>
      or = -2.5 SD) BMD levels in all groups except the spine in men. CONCLUSIONS: The
      levels of NTX uniquely discriminated between older adults with normal,
      osteopenic, or osteoporotic BMD levels. If confirmed, these data suggest that NTX
      levels could be used to predict current osteoporosis in older men and women.

PMID- 9183237
TI  - Mealtime treatment with insulin analog improves postprandial hyperglycemia and
      hypoglycemia in patients with non-insulin-dependent diabetes mellitus.
      Multicenter Insulin Lispro Study Group.
AB  - BACKGROUND: Insulin lispro is an insulin analog that was recently developed
      particularly for a mealtime therapy. It has a fast absorption rate and short
      duration of action. The efficacy of insulin lispro in the clinical therapy of
      patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been
      tested. OBJECTIVES: To compare insulin lispro and human regular insulin in the
      mealtime treatment of patients with NIDDM. METHODS: A 6-month, randomized,
      multinational (16 countries), multicenter (80 sites) clinical trial with an open
      label, crossover design was performed in 722 patients with NIDDM. Insulin lispro
      was injected immediately before and human regular insulin 30 to 45 minutes before
      the meal. RESULTS: Throughout the study, the postprandial rise in serum glucose
      levels was significantly lower during insulin lispro than human regular insulin
      treatment. At end point the rise (mean +/- SEM) in serum glucose levels was 30%
      lower at 1 hour (2.6 +/- 0.1 mmol/L [46.8 +/- 1.8 mg/ dL] for lispro vs 3.7 +/-
      0.1 mmol/L [66.6 +/- 1.8 mg/dL] for human regular insulin) and 53% lower 2 hours
      after the test meal (1.4 +/- 0.1 mmol/L [25.2 +/- 1.8 mg/dL] for lispro vs 3.0 +/
      0.1 mmol/L [54.0 +/- 1.8 mg/dL] for human regular insulin) with insulin lispro
      compared with human regular insulin therapy (P < .001 for both intervals). During
      insulin lispro therapy the rate of hypoglycemia overall (P = .01) and overnight
      (P < .001) was lower and the number of asymptomatic hypoglycemic episodes was
      smaller (P = .03) than during human regular insulin therapy. Associated with a
      similar 13% increase (P < .001) in the total daily insulin dose, the glycosylated
      hemoglobin level decreased (P < .001) equally in both treatment groups. Serum
      lipid and lipoprotein levels remained unchanged. There were no differences in the
      adverse events between the 2 treatment groups. CONCLUSIONS: Compared with human
      regular insulin therapy, mealtime therapy with insulin lispro reduced
      postprandial hyperglycemia and may decrease the rate of mild hypoglycemic
      episodes in patients with NIDDM.

PMID- 9183239
TI  - Use of amantadine for chronic fatigue syndrome.

PMID- 9183238
TI  - Paraneoplastic cerebellar degeneration. Case report and literature review.
AB  - Paraneoplastic cerebellar degeneration (PCD) presents with acute or subacute
      onset of ataxia, dysarthria, and intention tremor. In patients older than 50
      years, acute or subacute cerebellar degeneration is paraneoplastic in origin in
      50% of cases. Paraneoplastic cerebellar degeneration most often precedes a
      potentially curable remote malignancy. Less often, PCD occurs in a patient with a
      known malignancy or heralds the onset of a recurrence. The presence of specific
      antibodies in serum samples helps to guide identification of the occult
      underlying malignancy. Physicians should entertain the diagnosis of PCD when
      older patients present with signs of cerebellar degeneration without an obvious
      cause. A systematic evaluation, including the selection of appropriate imaging
      and laboratory studies, will often enable physicians to identify the responsible
      cancer. However, because PCD can precede a cancer by months to years, periodic
      reevaluation is needed when the cancer remains occult.

PMID- 9183240
TI  - Exacerbation of atherosclerosis by hypertension: potential mechanisms and
      clinical implications.

PMID- 9183241
TI  - Analysis of ROC curves applied to the diagnosis of Lyme disease.

PMID- 9183242
TI  - Bilateral pleural effusion and mortality: how does this compare with other risk
      factors?

PMID- 9183243
TI  - Intervention after myocardial infarction.

PMID- 9183244
TI  - Relative risk of sudden cardiac death during marathon running.

PMID- 9183245
TI  - Fluoxetine is a safer alternative to fenfluramine in the medical treatment of
      obesity.

PMID- 9183246
TI  - Efficacy, stability and predictors of outcome of pallidotomy for Parkinson's
      disease. Six-month follow-up with additional 1-year observations.
AB  - We tested the efficacy, stability and predictors of outcome of unilateral
      pallidotomy used to treat patients with Parkinson's disease inadequately
      controlled with pharmacotherapy (IP). The surgical procedure was as simple as
      possible; we used CT rather than MRI, and we omitted microelectrode recording. We
      studied 24 patients with IP; 22 of these patients had drug-induced dyskinesias.
      There was a significant and stable improvement in all the major parkinsonian
      motor signs in the OFF (medication) state on the contralateral side. In the ON
      (medication) state peak-dose dyskinesias were alleviated on the contralateral
      side. The only significant and stable change on the ipsilateral side was
      improvement in dyskinesias less marked than on the contralateral side. The
      improvement in Unified Parkinson's Disease Rating Scale motor scores in the OFF
      state increased with age. The improvement in total dyskinesia scores occurred
      irrespective of age, but increased with duration of disease, duration of
      dyskinesias and baseline severity of dyskinesias. Five patients had transient
      neurological complications while facial paresis was permanent in one subject. Our
      results are similar to those obtained by others who used the time consuming
      microelectrode recording technique for localization. By simplifying the procedure
      in the way that we describe, the operation could become available to a greater
      number of patients.

PMID- 9183247
TI  - Phonological and orthographic components of word recognition. A PET-rCBF study.
AB  - Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical
      decision-making tasks were used with 15O PET to examine the neural correlates of
      phonological and orthographic processing in 14 healthy right-handed men (aged 18
      40 years). Relative to a visual-fixation control task, all four experimental
      tasks elicited a left-lateralized stream of activation involving the lingual and
      fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both
      pronunciation tasks activated the left superior temporal gyrus, with
      significantly greater activation seen there during phonological (pseudoword) than
      during orthographic (real word) pronunciation. The left inferior frontal cortex
      was activated by both decision-making tasks; more intense and widespread
      activation was seen there during phonological, than during orthographic, decision
      making, with the activation during phonological decision-making extending into
      the left insula. Correlations of reference voxels in the left superior temporal
      gyrus and left inferior frontal region with the rest of the brain were highly
      similar for the phonological and orthographic versions of each task type. These
      results are consistent with connectionist models of reading, which hypothesize
      that both real words and pseudowords are processed within a common neural
      network.

PMID- 9183248
TI  - Altered patterns of cerebral activity during speech and language production in
      developmental stuttering. An H2(15)O positron emission tomography study.
AB  - To assess dynamic brain function in adults who had stuttered since childhood,
      regional cerebral blood flow (rCBF) was measured with H2O and PET during a series
      of speech and language tasks designed to evoke or attenuate stuttering. Speech
      samples were acquired simultaneously and quantitatively compared with the PET
      images. Both hierarchical task contrasts and correlational analyses (rCBF versus
      weighted measures of dysfluency) were performed. rCBF patterns in stuttering
      subjects differed markedly during the formulation and expression of language,
      failing to demonstrate left hemispheric lateralization typically observed in
      controls; instead, regional responses were either absent, bilateral or
      lateralized to the right hemisphere. Significant differences were detected
      between groups when all subjects were fluent-during both language formulation and
      non-linguistic oral motor tasks-demonstrating that cerebral function may be
      fundamentally different in persons who stutter, even in the absence of
      stuttering. Comparison of scans acquired during fluency versus dysfluency-evoking
      tasks suggested that during the production of stuttered speech, anterior
      forebrain regions-which play an a role in the regulation of motor function-are
      disproportionately active in stuttering subjects, while post-rolandic regions
      which play a role in perception and decoding of sensory information-are
      relatively silent. Comparison of scans acquired during these conditions in
      control subjects, which provide information about the sensorimotor or cognitive
      features of the language tasks themselves, suggest a mechanism by which fluency
      evoking maneuvers might differentially affect activity in these anterior and
      posterior brain regions and may thus facilitate fluent speech production in
      individuals who stutter. Both correlational and contrast analyses suggest that
      right and left hemispheres play distinct and opposing roles in the generation of
      stuttering symptoms: activation of left hemispheric regions appears to be related
      to the production of stuttered speech, while activation of right hemispheric
      regions may represent compensatory processes associated with attenuation of
      stuttering symptoms.

PMID- 9183249
TI  - Spatial and temporal auditory processing deficits following right hemisphere
      infarction. A psychophysical study.
AB  - Higher auditory function in a patient was investigated following a right
      hemisphere infarction between the middle and posterior cerebral artery
      territories involving the insula. The patient complained of lack of musical
      appreciation and a battery of tests confirmed a dissociated receptive musical
      deficit in the presence of normal appreciation of environmental sounds and
      speech. The ability to detect continuous changes in sound frequency in the form
      of sinusoidal frequency modulation was preserved. There was, however, a deficit
      in the analysis of rapid temporal sequences of notes which could underlie his
      musical deficit. This case provides further evidence for the existence of amusia
      as a distinct form of auditory agnosia, but does not support the hypothesis that
      bilateral lesions are required to produce such a deficit. Unexpectedly, the
      patient was also found to have a deficit in the perception of apparent sound
      source movement. We suggest that this deficit is analogous to the visual
      phenomenon of akinetopsia, and is in accord with PET work suggesting involvement
      of areas outside primary auditory cortex in sound movement perception. A possible
      common deficit in auditory temporal and spatial 'scene analysis' is discussed.

PMID- 9183250
TI  - Blindsight in hemispherectomized patients as revealed by spatial summation across
      the vertical meridian.
AB  - The present study provides a demonstration of blindsight in two hemispherectomy
      patients who showed a visual spatial summation effect across the vertical
      meridian despite their lack of visual awareness in one hemifield. Such an effect
      cannot be related to light diffusion onto the sighted hemifield because it was
      not present when one of the stimuli fell into the retinal blind spot of control
      subjects. We conclude that blindsight phenomena of the simple type described in
      the present study can be subserved by sub-cortical mechanisms and do not
      necessarily require cortical processing.

PMID- 9183251
TI  - Acetazolamide-responsive episodic ataxia in an Italian family refines gene
      mapping on chromosome 19p13.
AB  - Episodic ataxia type 2 is an autosomal dominant disorder with attacks of vertigo
      and ataxia which respond to acetazolamide treatment. The gene, distinct from the
      KCNA1 responsible for episodic ataxia type 1, has been mapped on chromosome 19p13
      in a 11-12 cM region. A large Italian kindred affected with acetazolamide
      responsive episodic ataxia is reported, with onset in adulthood, a strong
      vestibular component during attacks and a high frequency of cerebellar vermis
      degeneration. The genetic analysis (i) showed strong linkage between the disease
      and the 19p13 microsatellite markers in a region which widely overlaps that
      previously reported and (ii) set a new distal boundary of the gene-containing
      region. Combining present and previous mapping data, the gene of episodic etaxia
      type 2 is most probably located in an interval approximately 1.5 Mb between
      markers D19S221 and D19S226.

PMID- 9183252
TI  - Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and
      electrophysiological phenotype study and factors influencing disease severity in
      119 cases.
AB  - A clinical and electrophysiological study was performed in 119 Type 1A Charcot
      Marie-Tooth disease (CMT1A) patients with proven 17p11.2 duplication. Onset of
      the first functional manifestations was in the first decade in 50% of cases and
      before the age of 20 years in 70% of cases. The predominant clinical signs were
      muscle weakness and wasting in the lower limbs. None of the patients was normal
      on clinical examination and all presented at least pes cavus or ankle jerk
      areflexia. Motor nerve conduction velocity (MNCV) was uniformly reduced in all
      nerves, and was < or = 33 m/s in the median nerve for all patients. Sensory
      potentials were abnormal in all cases, even where there was no clinical sensory
      loss. Needle electromyography recruitment was reduced in distal muscles for all
      patients. MNCV slowing was fully consistent with the presence of duplication even
      in clinically asymptomatic individuals or in children, confirming the complete
      electrophysiological penetrance of 17p11.2 duplication and making median nerve
      MNCV a reliable tool for screening affected at-risk individuals. Functional
      disability was mild. Ninety-six percent of patients were autonomous; 25% were
      asymptomatic and diagnosed by systematic family investigation especially on the
      basis of median nerve MNCV reduction. Early age at onset and greatly reduced
      median nerve MNCV were predictive of a more severe disease course; the earlier
      the onset the more reduced the median nerve MNCV and the higher the functional
      disability tended to be after an equivalent disease duration. Cross-sectional
      analysis of neurological deficit, functional deficit and MNCV according to
      disease duration showed that, regardless of age at onset, CMT1A disease with
      17p11.2 duplication is a clinically progressive disorder. Neurological deficit
      and functional disability increased, whereas median nerve MNCV and compound
      muscle action potential (CMAP) amplitude did not change with disease course.
      Intrafamilial phenotype variation between parents and children and between
      siblings was studied in large families. Functional disability and neurological
      deficit differed widely and the highest range of median nerve MNCV within a
      family reached 23 m/s. Clinical and electrophysiological data were compared with
      those of CMT1B patients with peripheral myelin P0 protein point mutation. CMT1A
      patients were found to be more severely affected with more prolonged distal motor
      latency and more reduced CMAP amplitude, whereas MNCV did not significantly
      differ, indicating that peripheral myelin P0 protein point mutation is not always
      associated with a severe phenotype. The same genetic defect (17p11.2 duplication)
      results in variable expression within the phenotype, even in siblings with
      variations in age at onset, clinical severity and MNCV slowing. This phenotypic
      variation could be due to additional genetic factors related to peripheral myelin
      protein 22 expression as well as to other endogenous or environmental factors.

PMID- 9183253
TI  - Muscle activity adapts to anti-gravity posture during pedalling in persons with
      post-stroke hemiplegia.
AB  - With hemiplegia following stroke, a person's movement response to anti-gravity
      posture often appears rigid and inflexible, exacerbating the motor dysfunction. A
      major determinant of pathological movement in anti-gravity postures is the
      failure to adapt muscle-activity patterns automatically to changes in posture.
      The aim of the present study was to determine whether the impaired motor
      performance observed when persons with hemiplegia pedal in a horizontal position
      is exacerbated at more vertical anti-gravity body orientations. Twelve healthy
      elderly subjects and 17 subjects with chronic (> 6 months) post-stroke hemiplegia
      participated in the study. Subjects pedalled a modified ergometer at different
      body orientations (from horizontal to vertical), maintaining the same workload,
      cadence, and hip and knee kinematics. Pedal reaction forces, and crank and pedal
      kinematics, were measured and then used to calculate the work done by each leg
      and their net positive and negative components. The EMG was recorded from four
      leg muscles (tibialis anterior, medial gastrocnemius, rectus femoris and biceps
      femoris). The main result from this study was that impaired plegic leg
      performance, as measured by net negative work done by the plegic leg and abnormal
      early rectus femoris activity, was exacerbated at the most vertical body
      orientations. However, contrary to the belief that muscle activity cannot adapt
      to anti-gravity postures, net positive work increased appropriately and EMG
      activity in all muscles showed modulated levels of activity similar to those in
      elderly control subjects. These results support the hypothesis that increased
      verticality exacerbates the already impaired movement performance. Yet, much of
      the motor response to verticality was flexible and appropriate, given the
      mechanics of the task.

PMID- 9183254
TI  - Comparison of activation of corticospinal neurons and spinal motor neurons by
      magnetic and electrical transcranial stimulation in the lumbosacral cord of the
      anaesthetized monkey.
AB  - To illuminate the action of non-invasive stimuli on the human cerebral cortex,
      responses of corticospinal axons and of plantar alpha-motor neurons following
      transcranial magnetic (TMS) and electrical stimulation (TES) were recorded in the
      lumbosacral cord in the anaesthetized macaque monkey. A round coil was used for
      TMS, and the anode was located at the vertex for TES. The responses of 175
      identified corticospinal axons (conduction velocities of 24-95 m/s) were recorded
      from the lateral corticospinal tract at the T12-L3 spinal level. A single
      magnetic or electrical stimulus could evoke an early spike corresponding to the
      direct (D) wave in surface recorded volleys and was termed a D response. In the
      same axon, up to four further spikes, termed indirect (I) responses, could also
      be evoked. At a given intensity of stimulation, D responses had clear thresholds
      and fixed latencies, whereas I responses were labile in both respects. For TMS
      and TES, the thresholds of both D and I responses were inversely correlated with
      axonal conduction velocity. For TMS, fast conducting axons (> 75 m/s) had lower
      thresholds for D responses, while more slowly conducting axons (< 55 m/s) had
      lower thresholds for I responses. Very few of the axons with a conduction
      velocity of < 40 m/s (three out of 23) gave a D response to TMS. For TES, the
      majority of axons had lower thresholds for D responses or a similar threshold for
      both D and I responses. At threshold, the latencies of D responses evoked by TMS
      and TES were consistent with activation within the cortex, while TES also excited
      some corticospinal axons deep to the cortex. At 2.5 times threshold for the D
      response, TMS still excited axons mostly within the cortex, but with TES the site
      of activation shifted by as much as 65 mm below the cortex (mode 20 mm).
      Intracellular responses were recorded in 23 plantar alpha motor neurons supplying
      intrinsic muscles of the foot. All showed monosynaptic excitatory post-synaptic
      potentials (EPSPs) to both TMS and TES with no significant differences in the
      rise times of the evoked EPSPs. At threshold for a surface corticospinal volley,
      the average EPSP to TES began 0.5 ms earlier than that to TMS, and 1.0 ms earlier
      at 2.5 times this threshold. The different sites of activation of corticospinal
      neurons by TMS and TES, as well as the different distribution of D and I
      responses that they evoke, may both contribute to the differences in the onset
      latencies of the EMG responses evoked by these methods in human subjects.

PMID- 9183256
TI  - Biotechnological agents for the immunotherapy of multiple sclerosis. Principles,
      problems and perspectives.
AB  - Based on exciting results in animal models, a number of novel immunotherapies
      employing biotechnological products, rather than conventional immunosuppressants,
      are being developed for the treatment of multiple sclerosis. The first part of
      this article is a review of some fundamental concepts of immunology and offers a
      hypothetical scenario for the immunopathogenesis of multiple sclerosis. The
      second part provides a critical overview of various immunotherapies relying on
      modern biotechnology. For each approach, the underlying immunological principles,
      experimental and clinical evidence, and foreseeable problems are separately
      addressed. Thus, it is hoped that this article serves a dual purpose, namely to
      provide an update on recent advances in immunology, and to serve as a useful
      source of reference to immunotherapies holding promise for future treatment of
      multiple sclerosis.

PMID- 9183255
TI  - Supplementary sensorimotor area epilepsy. Seizure localization, cortical
      propagation and subcortical activation pathways using ictal SPECT.
AB  - We studied clinical signs, EEGs and ictal cerebral blood flow by single-photon
      emission computed tomography (SPECT) in eight patients with intractable
      supplementary sensorimotor area (SSMA) seizures. SPECT scans were performed after
      injection of the regional cerebral blood flow tracer [99mTc]HMPAO
      (hexametylpropylene amine oxime) early in the ictal phase (2-5 s after seizure
      onset). Ictal SPECT demonstrated unilateral predominance of hyper-perfusion of
      the SSMA in all patients, concordant with either lateralizing clinical signs,
      lateralization of ictal scalp EEG or with the site of ictal onset of seizures,
      obtained from intracranial electrodes. Two distinctive cortical blood-flow
      propagation patterns were identified in SSMA seizures. The type I pattern
      consisted of primary involvement of the ipsilateral SSMA and dorsal premotor and
      motor cortex. The type II pattern consisted of bilateral but asymmetric mesial
      frontal propagation. Ictal contraversive head and eye movements were associated
      with a type I propagation pattern (P < 0.03). Activation of subcortical
      structures led to variable hyper-perfusion of the basal ganglia and thalamus.
      Contralateral cerebellar hyperperfusion was observed in all cases. We conclude
      that ictal SPECT is a useful method for seizure localization in patients with
      SSMA epilepsy. The observed heterogeneity of clinical features in SSMA epilepsy
      correlates with propagation to, and activation of, specific cortical structures,
      and is consistent with known anatomical interconnections between the SSMA,
      ipsilateral cortical and transcallosal cortical structures.

PMID- 9183257
TI  - They are improved, but are they better?

PMID- 9183258
TI  - Development and reliability of a system to classify gross motor function in
      children with cerebral palsy.
AB  - To address the need for a standardized system to classify the gross motor
      function of children with cerebral palsy, the authors developed a five-level
      classification system analogous to the staging and grading systems used in
      medicine. Nominal group process and Delphi survey consensus methods were used to
      examine content validity and revise the classification system until consensus
      among 48 experts (physical therapists, occupational therapists, and developmental
      pediatricians with expertise in cerebral palsy) was achieved. Interrater
      reliability (kappa) was 0.55 for children less than 2 years of age and 0.75 for
      children 2 to 12 years of age. The classification system has application for
      clinical practice, research, teaching, and administration.

PMID- 9183259
TI  - Bone density and other possible predictors of fracture risk in children and
      adolescents with spastic quadriplegia.
AB  - Forty-three patients with spastic quadriplegia (mean age 7.9 years, range 3.3 to
      17.2 years) underwent bone mineral density (BMD) measurement of the lumbar spine
      and were evaluated between 2.6 and 5.5 years (mean 3.8) later to determine
      whether this measurement had predicted risk of fracture over the subsequent
      period of observation. Other potential risk factors that were evaluated include
      body weight z score, serum vitamin D levels, previous fracture, and hip spica
      casting. The baseline measurements showed that BMD falls further below normal
      with increasing age and was more than one standard deviation below age-matched
      normal mean in 38 of the 43 patients. Fracture rate did not differ between those
      with low and those with very low spinal BMD. Similarly, serum vitamin D levels
      and body weight z scores were not predictive of fracture. However, fracture rate
      was over fourfold greater following spica casting and more than threefold greater
      following an initial fracture. Fracture rates in the study group were similar to
      those reported for age- and sex-matched normal children, though generally the
      location of the fractures and mechanisms of injury differed.

PMID- 9183260
TI  - Gait analysis by measuring ground reaction forces in children: changes to an
      adaptive gait pattern between the ages of one and five years.
AB  - The aim of this study was to look at the maturational profile of gait parameters
      by measuring ground reaction forces during independent walking in children. Fifty
      four normal children aged 1 to 5 years were examined. The children walked with
      eight force transducers under each sole. Gait velocity and step length increased
      with age, whereas step frequency remained relatively constant. Phases of double
      ground contact expressed as percentages of the total gait cycle decreased
      significantly from age 1 to 5 with the steepest decrease occurring in the first
      year of independent walking. No asymmetry between left and right could be
      detected for any of these parameters. The pattern of ground reaction forces with
      a significant heel strike and obvious enrollment process resembling that in
      adults was achieved between the age of 2 and 3 years. Measuring ground reaction
      forces is a fast and easily manageable method of analysing gait pattern in
      children and is also a promising tool for detection of gait abnormalities in
      children with neurological disease.

PMID- 9183261
TI  - The influence of flexed-knee gait on the energy cost of walking in children.
AB  - There is an understanding that walking with flexed knees contributes to the
      increased energy cost of walking found in children with neurological conditions.
      To determine the influence of flexed-knee gait on energy cost of walking in a
      group of children without neurological abnormality, the gait patterns of 10
      normal children were studied using a Vicon system and standard marker set. A
      telemetric system (Cosmed K2) was then used to measure the oxygen cost of walking
      of the same children. The tests were repeated restricting the subjects' knee
      extension bilaterally, using hinged braces, set to 0, 15, 30, and 45 degrees of
      flexion. Although the braces themselves caused a significant increase in O2 cost
      (mL/kg/m) (P < 0.05), due to a decrease in walking speed, no further significant
      increase in oxygen cost was demonstrated regardless of the degree of knee flexion
      imposed, despite a significant increase in measured hip flexion and ankle
      dorsiflexion at the 45 degrees of knee flexion setting (P < 0.05). We propose
      that moderate flexed-knee gait does not of itself cause an increase in the energy
      cost of walking and that other factors present in the physically disabled child
      are likely to be implicated.

PMID- 9183262
TI  - Energy consumption in children with myelomeningocele: a comparison between
      reciprocating gait orthosis and hip-knee-ankle-foot orthosis ambulators.
AB  - This study compared the differences in energy efficiency (energy cost) in
      children with myelomeningocele ambulating with either reciprocating gait orthoses
      (RGOs) or hip-knee-ankle-foot orthoses (HKAFOs). There were 15 children who
      ambulated with RGOs and 11 children braced and ambulating in HKAFOs. Velocity was
      measured in m/s, energy consumption was measured in mL/kg/min, and energy cost
      (energy consumption/velocity) was measured in mL/kg/m. Children in HKAFOs had a
      significantly higher energy consumption rate than children in RGOs. However,
      children who swing through in a HKAFO have a significantly faster velocity than
      children who ambulate with the RGO using a reciprocating pattern. The increased
      energy cost in the RGO group is influenced by their slower velocity, just as the
      decreased energy cost in the HKAFO group is influenced by their increased
      velocity. Therefore it appears that children in HKAFOs are more energy efficient
      than children in RGOs.

PMID- 9183263
TI  - A preliminary evaluation of ankle orthoses in the management of children with
      cerebral palsy.
AB  - The effectiveness of ankle-foot orthoses (AFOs) on walking pattern was studied in
      12 children with cerebral palsy between the ages of 3 and 7 years. Over a 2-year
      period two trials of fortnightly periods without AFOs were carried out. The range
      of ankle dorsiflexion, video analysis looking specifically at footfall, and rank
      scoring of the mediolateral shear force obtained using an oscilloscope printout
      from a Kistler force platform were compared with measurements obtained during
      periods when the child was wearing AFOs. The results using different outcomes
      were consistent, and indicated that the range of movement and gait deteriorated
      during the two trial periods during which the splints were not worn compared with
      periods during which the splints were worn. This finding needs to be confirmed in
      a large randomised controlled trial.

PMID- 9183264
TI  - Laterality of finger movements in preterm infants.
AB  - The laterality of head position, spontaneous finger movements, hand-face contact,
      and hand-mouth contact was studied in low-risk preterm infants of 31 to < 37
      weeks postconceptional age (intrauterine + neonatal period at time of study). The
      head was predominantly turned towards the right side during the preterm period.
      Hand-mouth contact was more frequent on the right side and coincided well with
      the side to which the head was turned. Other hand movements, too, were more
      frequent on the right side than on the left, but these were also seen in the
      fingers contralateral to the direction in which the head was turned. These
      findings suggest that even before birth a spontaneous preference for head
      position is present and is already associated with asymmetry in coordinated
      finger movements.

PMID- 9183265
TI  - The outcome of walking in stable neuromuscular deficiencies.
AB  - In some patients with stable or very gradually worsening neuromuscular disorders,
      walking performance nevertheless decreases with increasing hip flexion and spinal
      deformity as the patient grows. The relations between muscular deficiency, pelvic
      and spinal deformity, head stability, gravity parameters and walking performance
      were studied in 43 patients aged 18 months to 38 years with a view to finding out
      how these parameters are related, whether progressive spinal deformity and loss
      of walking can be avoided or delayed, and whether specific therapy for each of
      these parameters can help. Early combating of hip flexion deformity by
      physiotherapy, accompanied by limbering-up exercises of the spine to counteract
      lumbar and thoracic lordosis are useful, as are orthoses to correct pelvic tilt
      anteversion, spinal lordosis and head instability. If physiotherapy is
      ineffectual or too late, tenoctomy of the rectus femoris may help.

PMID- 9183266
TI  - Prevalence and type of cerebral palsy in a British ethnic community: the role of
      consanguinity.
AB  - Little is known about the prevalence of cerebral palsy (CP) within ethnic
      subgroups born in Britain. The Yorkshire Regional Cerebral Palsy Register has
      ascertained all cases of CP in children born within the Regional Health Authority
      boundary in 1985 to 1987 inclusive and diagnosed by 5 years of age. Birth
      registrations recorded by ethnic subgroups allowed us to determine the prevalence
      of CP within the Bradford District Health Authority (BDHA) boundaries by Asian
      and non-Asian ethnic subgroups. All the children with CP in BDHA were examined by
      one individual and careful family pedigrees recorded. We noted that BDHA had a
      high prevalence of CP; 3.87 to 4.16 per 1000. The prevalences in the non-Asian
      and Asian populations were 3.18, and between 5.48 and 6.42, per 1000,
      respectively. This difference was statistically significant (P = 0.03). First
      cousin marriages occurred in 15 of the 39 Asian families (51.7%) and nine of
      these families had another first or second degree family member with a similar
      type of CP to the index child. There was no consanguinity in the non-Asian
      families. These data highlight the increased need for services in some ethnic
      populations living in Britain and the likely genetic aetiology of a significant
      proportion of cases of CP in Asian families.

PMID- 9183267
TI  - Medical and social factors associated with cognitive outcome in individuals with
      myelomeningocele.
AB  - The interrelationship between biological and social risk factors and cognitive
      outcome in individuals with myelomeningocele was examined. The Kaufman Brief
      Intelligence Test (K-BIT) was administered to 65 children and young adults, age
      range 4 to 29 during a recent clinic visit. Unshunted individuals had scores in
      the average range and individuals with uncomplicated hydrocephalus in the low
      average range. Although the level of lesion was found to be most strongly
      associated with total K-BIT score, examination of subscores indicated that
      socioeconomic status was the factor most strongly associated with Vocabulary
      score. The importance of both social and biological factors in predicting
      cognitive outcome in this population is useful in planning intervention
      strategies.

PMID- 9183268
TI  - Resolution of subependymal cysts in neonatal holocarboxylase synthetase
      deficiency.
AB  - Holocarboxylase synthetase deficiency is typically a biotin responsive disorder
      that presents with lactic acidosis, tachypnea, temperature instability, and shock
      in neonates (Briones et al.1989 and Fuchshuber et al. 1992). The primary defect
      in cases studied to date appears to be the decreased affinity of HCS for its
      substrate, biotin (Gompertz et al. 1971). Supplemental biotin can provide
      sufficient substrate to increase HCS enzymatic function and thereby permit
      biotinylation of the four carboxylase apoenzymes (Briones et al. 1989). We report
      an infant with HCS deficiency who presented with lactic acidosis, shock, and
      hypertonia. Subependymal cysts were identified on cranial ultrasound and
      subsequently confirmed by MRI. Six months following biotin supplementation, she
      is developmentally normal and MRI of the brain shows complete resolution of the
      cysts.

PMID- 9183269
TI  - Eye movement abnormalities in a case of Tourette syndrome.
AB  - Tourette syndrome (TS) is a neuropsychiatric disorder that is characterised by
      the presence of multiple vocal, facial, and motor tics which change with time,
      and a number of other behavioural phenomena. Previous studies have not revealed
      any ocular-motor abnormalities. We report the eye movement studies of a patient
      with TS, using electrooculography and simultaneous video recording. Intrusive
      saccades occurred during smooth pursuit and optokinetic nystagmus. Reflexive and
      voluntary saccades were dysmetric and there was a complete failure of
      antisaccades. These abnormalities are characteristic of disease of the frontal
      lobes and basal ganglia. We review the literature with respect to the eye
      movement abnormalities associated with TS.

PMID- 9183270
TI  - Fetal habituation: another Pandora's box?

PMID- 9183271
TI  - 'Otitis media with effusion'.

PMID- 9183272
TI  - 'Asperger syndrome associated with Steinert's myotonic dystrophy'.

PMID- 9183273
TI  - Prehospital pearls, pitfalls, and updates.
AB  - The rapid proliferation of emergency medical services in the United States has
      led to numerous controversies concerning delivery, interventions, and efficacy.
      This article presents a brief overview of the important literature in this
      expanding field. Important clinical topics, including first-responder
      defibrillation, rapid sequence intubation, and airway management, are reviewed.
      In addition, several important medicolegal topics pertaining to pre-hospital care
      are analyzed.

PMID- 9183274
TI  - The clinical practice of emergency medicine.
AB  - This article provides brief updates, pearls, and pitfalls on aspects of emergency
      practice that are dealt with routinely, including the application of diagnostic
      testing in the emergency department, ruling out subarachnoid hemorrhage, and the
      use of tympanic temperatures. Physician-patient and physician-physician
      communication skills are addressed. Finally, medicolegal and administrative
      topics, such as EMTALA, writing admitting orders, treating minors in the
      emergency department, and blood product therapy in Jehovah's Witnesses are also
      discussed.

PMID- 9183275
TI  - Respiratory pearls, pitfalls, and updates.
AB  - The scope of respiratory and ventilatory support offered in the emergency
      department (ED) has expanded substantially in the last 10 years. Emergency
      physicians are now much more aggressive and sophisticated in their management of
      bronchospasm, pulmonary edema, and acute respiratory failure. New medications and
      new technologies that have been tested in intensive care units should also be
      considered appropriate for use in the ED; indeed, from a respiratory support
      standpoint, the ED should be viewed as an intensive care unit. In this article,
      the authors outline these new concepts and treatments that allow initiation of
      "intensive care" in the ED.

PMID- 9183276
TI  - Eye, ear, nose, and throat.
AB  - Patients present to the emergency department with a number of eye, ear, nose, and
      throat (ENT) problems. This article updates some very common problems; identifies
      a few pearls on nasal foreign body removal, ophthalmologic medication, and
      epistaxis; and reviews a few pitfalls in identifying malignancies and sore
      throats.

PMID- 9183277
TI  - Cardiology.
AB  - Emergency cardiac problems are a frequent and significant occurrence in the daily
      life of the emergency physician. The first part of this article discusses some of
      the pearls and pitfalls of caring for the cardiac patient ranging from treating
      wide-complex tachycardia and troubleshooting pacemaker malfunction to diagnosing
      acute myocardial infarction in the setting of bundle branch blocks. The second
      part of this article updates the reader on several of the newer technologies and
      treatments, such as transesophageal echocardiography and intravenous amiodarone,
      now in use in the emergency department setting.

PMID- 9183278
TI  - The extremities and spine.
AB  - A variety of pearls, pitfalls, and updates related to the extremities and spine
      are discussed. Tricks of the trade regarding shoulder dislocations, easily missed
      fractures, radial head subluxation, and the approach to deep lacerations are
      discussed. In the pitfall section, potential difficulties in the evaluation of
      suspected nonaccidental trauma, compartment syndromes, partial cord syndromes,
      and hip pain in children are discussed. Finally, new information regarding cost
      effective evaluation of knee and ankle injuries, as well as advances in
      ultrasound evaluation of shoulder and extremity injuries, is presented in the
      clinical updates section.

PMID- 9183279
TI  - Pediatrics. A potpourri of clinical pearls.
AB  - A pediatric focus in the emergency department requires an understanding of age
      specific parameters of assessment and management. Differential considerations are
      unique in the pediatric patient reflecting both congenital and acquired
      conditions. Respiratory problems, meningitis, seizures, and child abuse require
      careful assessment and aggressive intervention. When approaching the ill child,
      attention must be directed toward reducing anxiety and pain in the patient.

PMID- 9183280
TI  - Obstetric and gynecologic emergencies.
AB  - This article reviews the pearls and pitfalls of obstetric and gynecologic
      emergencies occurring in women presenting to the emergency department. Some
      pitfalls include failure to screen for ectopic pregnancy, tachycardia as an
      unreliable indicator of a ruptured ectopic pregnancy, and the use of serum hCG as
      a testing procedure during pregnancy. Updates include serologic markers of
      ectopic pregnancy, ultrasonography in the emergency department, methotrexate
      treatment of ectopic pregnancy, traumatic placental separation, and fetomaternal
      hemorrhage.

PMID- 9183282
TI  - Wound care.
AB  - Soft-tissue injuries remain one of the most common problems encountered in the
      emergency department. This article discusses techniques to minimize pain during
      the evaluation and repair process, methods to decrease healing complications, and
      repair considerations.

PMID- 9183281
TI  - Pearls, pitfalls, and updates for pain management.
AB  - Pain management is one of the most challenging areas we encounter as emergency
      physicians. However, many of us fail to adequately meet this challenge. This
      article discusses frequently encountered pain syndromes and pain management
      options.

PMID- 9183283
TI  - Pearls, pitfalls, and updates in toxicology.
AB  - Pearls and pitfalls learned from our practical experiences caring for poisoned
      patients are presented. Clinical pearls include the following: using diagnostic
      tests to detect end-organ toxicity, applying physiologic principles to the
      management of hemodynamically unstable poisoned patients, and dealing with
      psychologic injuries from hazardous materials incidents. Recognizing serious
      complications from poisoning and adverse drug effects, including the serotonin
      syndrome, are offered as pitfalls. Pharmaceutical companies are rapidly
      developing and marketing new therapies. Therefore, updates on the evolving role
      of NAC as an antidote for acetaminophen poisoning, new psychotropic medications,
      and new antidotes were included in this article. These pearls, pitfalls, and
      updates are intended to provide practical information that is readily applicable
      to the clinical practice of emergency medicine.

PMID- 9183284
TI  - Environmental emergencies.
AB  - This article reviews the pearls and pitfalls of high-altitude sickness,
      decompression sickness, and barotrauma; new findings relevant to the near
      drowning patient; continued controversies on hyperbaric oxygen for carbon
      monoxide poisoning; pitfalls in hypothermia management; and updates on the
      management of venomous snakebites.

PMID- 9183285
TI  - TNF-alpha pretreatment induces protective effects against focal cerebral ischemia
      in mice.
AB  - Cytokines are recognized to play an important role in acute stroke. Tumor
      necrosis factor-alpha (TNF) is one of the pro-inflammatory cytokines and is
      expressed in ischemic brain. We hypothesized that TNF might play a role in the
      regulation of tolerance to ischemia when administered prior to the ischemic
      episode. We studied the effects of pretreatment of TNF administered
      intravenously, intraperitoneally, or intracisternally in mice that were subjected
      to middle cerebral artery occlusion (MCAO) 48 h later. MCAO was performed in
      BALB/C mice by direct cauterization of distal MCA, which resulted in pure
      cortical infarction. A significant reduction in infarct size was noted in mice
      pretreated by TNF at the dose of 0.5 microgram/mouse (p < 0.01) intracisternally.
      At the doses used in this study, administration of TNF by intravenous or
      intraperitoneal routes was not effective. Immunohistochemical analysis of brains
      subjected to 24 h of MCAO revealed a significant decrease in CD11b
      immunoreactivity after TNF pretreatment compared with control MCAO.
      Preconditioning with TNF affects infarct size in a time- and dose-dependent
      manner. TNF induces significant protection against ischemic brain injury and is
      likely to be involved in the signaling pathways that regulate ischemic tolerance.

PMID- 9183286
TI  - Induction of tumor necrosis factor-alpha in the mouse hippocampus following
      transient forebrain ischemia.
AB  - To assess the role of tumor necrosis factor-alpha (TNF-alpha) in modulating the
      process of cerebral ischemic injury, we identified TNF-alpha-producing cells and
      studied the time course of TNF-alpha expression. Immunoreactivity for TNF-alpha
      appeared in white matter of the mouse hippocampus as early as 1.5 h following a
      30-min global ischemic insult. Double staining for TNF-alpha and glial fibrillary
      acidic protein (GFAP) suggested that the TNF-alpha-positive cells are most likely
      microglia, not astrocytes. TNF-alpha immunostaining decreased at 6 and 24 h but
      increased again at 3 days, when pyramidal neurons showed degeneration. Adjacent
      section staining for microglia and double staining with GFAP suggested that TNF
      alpha-positive cells in the pyramidal cell layer were microglia and those in the
      white matter were astrocytes. By 5 days TNF-alpha immunostaining disappeared from
      these glial cells, while a number of microglia were accumulated in the
      degenerated hippocampal pyramidal layer. Pyramidal neurons never expressed TNF
      alpha immunoreactivity. Western blotting confirmed biphasic TNF-alpha expression.
      Our findings suggest that early production of TNF-alpha by microglia may activate
      a cytokine network in post-ischemic brain resulting in TNF-alpha synthesis by
      astrocytes.

PMID- 9183287
TI  - Intraventricular brain-derived neurotrophic factor reduces infarct size after
      focal cerebral ischemia in rats.
AB  - Brain-derived neurotrophic factor (BDNF), acting through the high-affinity
      receptor tyrosine kinase (TrkB), is widely distributed throughout the central
      nervous system and displays in vitro trophic effects on a wide range of neuronal
      cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF
      rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from
      traumatic and toxic brain injury. After transient middle cerebral artery
      occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that
      BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the
      current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was
      delivered intraventricularly for 8 days, beginning 24 hours before permanent
      middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13
      per group). There were no differences in physiological variables recorded during
      surgery for the two groups. Neurological deficit (0 to 4 scale), which was
      assessed on a daily basis, improved in BDNF-treated animals compared with
      controls (P < 0.05; analysis of variance and Scheffe's test). There were no
      significant differences in weight in BDNF-treated animals and controls during the
      experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5
      triphenyltetrazolium chloride staining for calculation of the infarct volume and
      for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean
      total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/-
      56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The
      cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/-
      19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test),
      whereas ischemic lesion volume in caudoputaminal infarction was not significantly
      different. These results show that pretreatment with intraventricular BDNF
      reduces infarct size after focal cerebral ischemia in rats and support the
      hypothesis of a neuroprotective role for BDNF in stoke.

PMID- 9183288
TI  - Up-regulation of the Nedd2 gene encoding an ICE/Ced-3-like cysteine protease in
      the gerbil brain after transient global ischemia.
AB  - We assessed the expression of several genes encoding pro-apoptotic cysteine
      proteases similar to interleukin-1 beta converting enzyme (ICE) and nematode Ced
      3 in association with delayed neuronal death (DND) after transient forebrain
      ischemia in Mongolian gerbil. The levels of the two species of Nedd2 mRNA
      concomitantly increased about two-fold in the whole forebrain at 3-6 h after 10
      min ischemia and declined to the basal level by 24 h. In situ hybridization
      revealed that the Nedd2 gene was up-regulated in some neuronal populations in CA1
      and CA3 regions of the hippocampus. In contrast, expression of ICE,
      CPP32/Yama/Apopain, and TX/ICErelll did not change within 48 h. These
      observations raise the possibility that up-regulation of Nedd2 in the vulnerable
      neurons may contribute to the proteolytic processes preceding the manifestation
      of apoptosis and/or necrosis after ischemic insult.

PMID- 9183289
TI  - [3H]L-NG-nitroarginine binding after transient focal ischemia and NMDA-induced
      excitotoxicity in type I and type III nitric oxide synthase null mice.
AB  - We investigated the density and distribution of nitric oxide synthase (NOS)
      binding by quantitative autoradiography using [3H]L-NG-nitroarginine ([3H]L-NNA)
      after transient focal ischemia or intrastriatal injection of N-methyl-D-aspartate
      (NMDA) in wild-type (SV-129 and C57black/6) and type I (neuronal) and type III
      (endothelial) NOS-deficient mice. The middle cerebral artery (MCA) was occluded
      by an intraluminal filament for 3 h followed by 10 min to 7 days of reperfusion.
      Specific [3H]L-NNA binding, observed in the wild-type and type III mutant mouse
      at baseline, increased by 50-250% in the MCA territory during ischemia and the
      first 3 h of reperfusion. The density of binding sites (Bmax), but not the
      dissociation constant (Kd), increased significantly during the ischemic period as
      did type I NOS mRNA as detected by quantitative reverse transcription polymerase
      chain reaction. [3H]L-NNA binding after intrastriatal NMDA injection also
      increased by 20-230%. In the type I NOS-deficient mouse, [3H]L-NNA binding was
      low and only a very small increase was observed after ischemia or excitotoxicity.
      Under conditions of this study, [3H]L-NNA did not bind to type II NOS as there
      was no difference in the distribution or density of [3H]L-NNA binding in the rat
      spleen obtained after lipopolysaccharide treatment despite induction of NOS type
      II catalytic activity. Our data suggest that an ischemic/excitotoxic insult up
      regulates type I NOS gene expression and [3H]L-NNA binding and that this up
      regulation may play a pivotal role in the pathogenesis of ischemic/excitotoxic
      diseases.

PMID- 9183290
TI  - Delayed neuronal death after global incomplete ischemia in dogs is accompanied by
      changes in phospholipase C protein expression.
AB  - Activation of phospholipase C (PLC) increases intracellular Ca2+ and may play a
      role in delayed neuronal death after ischemia. Because changes in intracellular
      Ca2+ are believed to participate in ischemic neuronal injury, we tested the
      hypothesis that PLC beta protein levels are temporally altered in brain regions
      that undergo neurodegeneration after global incomplete ischemia. Dogs (n = 12)
      were subjected to 20 minutes of global incomplete ischemia followed by recovery
      of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as
      nonischemic controls. In hematoxylin and eosin-stained brain sections, neuronal
      density at 1 day after ischemia was unchanged relative to nonischemic controls in
      hippocampus CA1, caudate, and cerebellar cortex (anterior lobule). However, at 7
      days after ischemia, neuronal densities were decreased to 56 +/- 15% (mean +/-
      SD) and 75 +/- 17% of control in CA1 and caudate, respectively. At 1 and 7 days
      after ischemia, the percentage of neurons showing ischemic injury increased from
      13 +/- 10 to 40 +/- 35% in CA1, 24 +/- 25 to 59 +/- 16% in cerebellum, and 4 +/-
      2 to 18 +/- 12% in caudate. Densitometric analysis of immunocytochemically
      stained brain sections from controls (n = 3). 1 day after ischemia (n = 3), and 7
      days after ischemia (n = 5) revealed that PLC beta immunoreactivity was increased
      in cerebellum at 1 day (0.274 +/- 0.013 v 0.295 +/- 0.005 optical density units
      [OD] in control and 1 day, respectively) and 7 days (0.108 +/- 0.009 v 0.116 +/-
      0.005 O.D. in control and 7 days, respectively). PLC beta immunoreactivity was
      unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLC
      beta immunoreactivity in the cerebellar cortex and hippocampus in the control (n
      = 3), 1 day (n = 2), and 7 days after ischemia (n = 2) groups showed that PLC
      beta levels were increased after ischemia in cerebellum 266% and 227% above
      control at 1 and 7 days, respectively. However, in hippocampus, PLC expression
      after ischemia was unchanged at 97% and 84% of control at 1 and 7 days,
      respectively. These results show that delayed neuronal degeneration after global
      incomplete ischemia is accompanied by regional abnormalities in PLC levels.
      Elevated PLC levels early may represent an aberrant signal transduction mechanism
      resulting in delayed cell damage, whereas decreased PLC levels later after
      ischemia may reflect ongoing neurodegeneration.

PMID- 9183291
TI  - Inhibition of nonselective cation channels reduces focal ischemic injury of rat
      brain.
AB  - The effect of the novel inhibitor of receptor-activated and calcium store
      operated nonselective cation channels, (RS)-(3,4-dihydro-6,7
      dimethoxyisoquinoline-1-gamma 1)-2-phenyl-N, N-di-[2(2,3,4-trimethoxyphenyl)
      ethyl]acetamide (LOE 908 MS), on focal cerebral ischemia was studied in halothane
      anesthetized rats submitted to permanent suture occlusion of the right middle
      cerebral artery (MCA). The treated group (n = 7) received subcutaneous injections
      of 30 mg/kg LOE 908 MS (in 1 ml saline) 10 min after vascular occlusion and again
      after 3 h. The untreated group (n = 11) was injected subcutaneously with 1 ml
      saline at the same times. Evolution of infarct was monitored by
      electrophysiological recording of EEG and cortical steady potential and by
      diffusion-weighted magnetic resonance imaging during the initial 6 h of vascular
      occlusion. The hemodynamic, biochemical, and morphological changes were studied
      after 6 h by combining autoradiographic measurement of blood flow with
      histological stainings and pictorial measurements of ATP, glucose, and tissue pH.
      In the untreated animals, the ischemic lesion volume [defined as the region in
      which the apparent diffusion coefficient (ADC) of water declined to below 80% of
      control] steadily increased by approximately 50% during the initial 6 h of
      vascular occlusion relative to the first set of data 10 min postocclusion. In the
      treated animals, in contrast, the ADC lesion volume declined by approximately 20%
      during the same interval. Treatment also led to a significant reduction in the
      number of periinfarct depolarizations. After 6 h of vascular occlusion, blood
      flow was significantly higher in the treated animals, and the volume of ATP
      depleted and morphologically injured tissue representing the infarct core was 60
      70% smaller. The volume of severely acidic tissue, in contrast, did not differ,
      indicating that LOE 908 MS does not reduce the size of ischemic penumbra. These
      findings demonstrate that postocclusion treatment of permanent focal ischemia
      with LOE 908 MS delays the expansion of the infarct core into the penumbra for a
      duration of at least 6 h and therefore substantially prolongs the window of
      opportunity for the reversal of the ischemic impact in the peripheral parts of
      the evolving infarct.

PMID- 9183292
TI  - Limited but significant protective effect of hypothermia on ultra-early-type
      ischemic neuronal injury in the thalamus.
AB  - We investigated the protective effect of hypothermia on ultra-early-type ischemic
      injury in the thalamic reticular nucleus of the rat. Cerebral ischemia was
      produced by 5 min of cardiac arrest followed by resuscitation. Rectal and cranial
      temperature during and after cardiac arrest was maintained at 37-38 degrees C in
      the normothermic group and at 32-33 degrees C in the hypothermic group. In the
      postischemic hypothermic group, temperature was maintained at 32-33 degrees C
      starting 15 min after normothermic ischemia. Histological damage was evaluated
      quantitatively. While after 5 min of recirculation there was no difference in
      morphological changes in terms of neuronal halo formation, intraischemic
      hypothermia reduced the severity of the degenerative changes represented by
      vacuolated or dark neurons by 15 min. Postischemic hypothermia failed to show any
      evidence of protection by 30 min. The protective effect of intraischemic
      hypothermia remained significant when evaluated at 14 days after ischemia by
      volumetry of the lesion and neuronal density analysis, whereas postischemic
      hypothermia had no clear protective effect. These results suggest that the
      protective effect of intraischemic hypothermia applies to neurons susceptible to
      ultra-early-type injury, but the effect of postischemic hypothermia is limited
      because normothermic ischemia results in extensive degeneration in these neurons
      by 15 min.

PMID- 9183293
TI  - Perfusion deficit parallels exacerbation of cerebral ischemia/reperfusion injury
      in hyperglycemic rats.
AB  - Magnetic resonance imaging (MRI) techniques were used to determine the effect of
      preexisting hyperglycemia on the extent of cerebral ischemia/reperfusion injury
      and the level of cerebral perfusion. Middle cerebral artery occlusion (MCAO) was
      induced by a suture insertion technique. Forty one rats were divided into
      hyperglycemic and normoglycemic groups with either 4 hours of continuous MCAO or
      2 hours of MCAO followed by 2 hours of reperfusion. Diffusion-weighted imaging
      (DWI) was performed at 4 hours after MCAO to quantify the degree of injury in 6
      brain regions. Relative cerebral blood flow (CBF) and cerebral blood volume (CBV)
      were estimated using gradient echo (GE) bolus tracking and steady-state spin echo
      (SE) imaging techniques, respectively. Brain injury correlated with the perfusion
      level measured in both SE CBV and dynamic GE CBF images. In the temporary MCAO
      model, mean lesion size in DWI was 118% larger and hemispheric CBV was reduced by
      37% in hyperglycemic compared with normoglycemic rats. Hyperglycemia did not
      significantly exacerbate brain injury or CBV deficit in permanent MCAO models. We
      conclude that preexisting hyperglycemia increases acute postischemic MRI
      measurable brain cellular injury in proportion to an associated increased
      microvascular ischemia.

PMID- 9183294
TI  - The influence of age of pH regulation in hippocampal slices before, during, and
      after anoxia.
AB  - Changes in intracellular and extracellular pH may influence the vulnerability of
      brain tissue to anoxic or ischemic damage. In the present study, we investigated
      whether the increased vulnerability of aged brain tissue to anoxic damage is
      associated with age-related alterations in pH regulation. We obtained evidence
      for altered pH regulation by measuring concurrent changes in intracellular and
      extracellular pH before, during, and after anoxia in hippocampal slices from
      young adult (6-8 months old) and aged (24-27 months old) rats. We found
      indications of impaired pH regulation in aged hippocampal slices (a) before
      anoxia, as seen in a lower resting intracellular pH, (b) during anoxia, as seen
      in a slower decline in extracellular pH, and (c) during recovery after anoxia, as
      seen in a slower rate of recovery of intracellular pH. Age-related changes in pH
      regulation may contribute to the faster onset of anoxic depolarization in aged
      brain tissue during anoxia.

PMID- 9183295
TI  - L-alpha-aminoadipate reduces glutamate release from brain tissue exposed to
      combined oxygen and glucose deprivation.
AB  - The effect of the glutamate analogue L-alpha-aminoadipate (alpha AA) on the
      release of glutamate and gamma-aminobutyric acid (GABA) from rat hippocampal
      slices was investigated in vitro. Oxygen/glucose deprivation caused a large
      release of glutamate and GABA. alpha AA added during energy deprivation reduced
      the glutamate release in a dose-dependent manner (56% reduction at 5 mM), whereas
      GABA release was unchanged. We speculate that ischemic glutamate release from the
      brain is mediated by a low affinity transport mechanism that is blocked by alpha
      AA.

PMID- 9183296
TI  - Rat strain and vendor differences in collateral anastomoses.
AB  - Recently we observed inter- and intrastrain differences in cortical infarct
      volumes after middle cerebral artery (MCA) occlusion. Variations in the
      anastomoses providing collateral blood supply could account for different lesion
      sizes. Our objectives were to compare number and internal diameters of the MCA
      anterior cerebral artery (MCA-ACA) anastomoses and to determine if the lesion
      extended beyond branches of the MCA territory into the field of the ACA in the
      rat strains/lines. Sprague-Dawley rats and Wistar rats from Simonsen Laboratories
      (SLSD and SLWIS) and Sprague-Dawley rats from Taconic Laboratories (TLSD) and
      Charles River Laboratories (CRSD) were anesthetized and injected with papaverine
      and Vultex (white latex) for arterial visualization. Some rats were also
      subjected to MCA occlusion. Significantly fewer anastomoses were present in SLSD
      and SLWIS than in CRSD and TLSD (p < 0.05). The mean internal diameters of the
      anastomoses were not significantly different between the strains/lines (p <
      0.05). After MCA occlusion, significantly more (p < 0.05) TLSD and CRSD than SLSD
      had lesions extending from the MCA field beneath the anastomoses and into the
      region supplied by the ACA. Neither the number, luminal diameter, nor density of
      MCA-ACA anastomoses appears to be the limiting factor that differentiates lesion
      size following MCA occlusion in these particular rat strains/lines. Therefore,
      factors other than anatomical variations probably account for different lesion
      sizes.

PMID- 9183297
TI  - Assessment of functional hemispheric asymmetry by bilateral simultaneous cerebral
      blood flow velocity monitoring.
AB  - The aim of this study was to investigate side-to-side differences of
      simultaneously measured middle cerebral artery (MCA) blood flow velocities during
      various hemisphere-specific tasks. Using a transcranial Doppler device, flow
      velocity changes of 24 healthy, right-handed subjects were monitored
      simultaneously in the left and right MCA during different hemisphere-specific
      tasks. Mean flow velocity (MFV) curves were averaged for each individual subject
      and task. Simultaneously, heart rate, blood pressure and end-tidal carbon dioxide
      (CO2) were measured in a subgroup of six subjects. When compared with the resting
      state, all stimuli produced significant (p < 0.001) bilateral MFV increases,
      ranging from 2.5-9.2%. A lateralization of MFV increases with a significantly (p
      < 0.001) more pronounced increase in MFV in the hemisphere contralateral to the
      performing band was observed both during simple sequential finger movements and a
      complex spatial task. During the complex spatial task, consistently higher MFV
      increases were observed in the right MCA (p < 0.001), regardless of the side of
      task performance. Recognition of pictorial material presented as part of a memory
      task, also resulted in a side-to-side difference of respective MFV increases
      (right > left, p < 0.001), whereas memorization did not. Whereas bilateral MFV
      elevations observed during stimulation with white noise were only discrete and
      not lateralized, exposure to overt speech produced significantly higher (p <
      0.001) MFV increases in the left MCA. The time course of the MFV reaction showed
      a rapid increase with an initial maximum after 4-5 s. Heart rate, blood pressure,
      and end-tidal CO2 showed only subtle changes during the stimulation periods. In
      conclusion, the observed side-to-side differences of MFV reaction in the left and
      right MCA concur with current functional imaging data. Bilateral simultaneous
      repetitive transcranial Doppler monitoring is a sensitive method to detect
      cerebral perfusion asymmetries caused by hemisphere-specific activation, and thus
      may be helpful for noninvasive assessment of hemispheric dominance for language.

PMID- 9183298
TI  - In vivo uptake of [3H]nimodipine into brain during cortical spreading depression.
AB  - We report autoradiographic measurements of the in vivo uptake of [3H]nimodipine
      during the nonischemic depolarization of cortical spreading depression (CSD) in
      rat brain. [3H]Nimodipine uptake in brain was determined regionally in rats
      undergoing CSD (n = 8) and was significantly increased in cortex (14 +/- 7%) and
      hippocampus (10 +/- 6%) on the stimulated side relative to the contralateral
      hemisphere when compared with the same measurements in a control group (n = 8). A
      similar measurement using the physiologically inert radiotracer
      [14C]iodoantipyrine to control for potential effects of CSD on radioligand
      distribution showed a minimal increase (2.4 +/- 0.7%) of radiotracer uptake in
      cortex after CSD. This increase was significantly less than that observed in the
      [3H]nimodipine uptake studies. We hypothesize that increased in vivo
      [3H]nimodipine uptake in CSD identifies regions of depolarization and thus infers
      activation of the L-type voltage sensitive calcium channels.

PMID- 9183299
TI  - Hyperglycemia delays terminal depolarization and enhances repolarization after
      peri-infarct spreading depression as measured by serial diffusion MR mapping.
AB  - We investigated the effect of hyperglycemia on the initiation and propagation of
      spreading depression-like peri-infarct ischemic depolarization (SD) induced by
      focal cerebral ischemia in rats. Peri-infarct SD were monitored during the
      initial 15 minutes after remotely induced middle cerebral artery occlusion (MCAO)
      using serial diffusion weighted magnetic resonance imaging. Maps of the apparent
      diffusion coefficient (ADC) were calculated and ADC decreases were monitored over
      time. Hyperglycemic rats (n = 6) had a significant prolongation of the time from
      induction of MCAO to the start of the ADC decrease as compared with normoglycemic
      control rats. The time to the maximal ADC decrease was significantly delayed and
      recovery of transient ADC declines in the area adjacent to the ischemic core was
      significantly faster in hyperglycemic rats. We conclude that hyperglycemia delays
      the terminal depolarization in the ischemic core and supports a faster
      repolarization in severely mal-perfused penumbral tissue after SD, which reflects
      the increased availability of energy substrates in the state of hyperglycemia.

PMID- 9183300
TI  - Treatment of obsessive-compulsive disorder. The Expert Consensus Panel for
      obsessive-compulsive disorder.

PMID- 9183301
TI  - Primary biliary cirrhosis.

PMID- 9183302
TI  - Microcirculation: its significance in clinical and molecular medicine.
AB  - Microcirculation represents the smallest functional unit of the cardiovascular
      system, where the interaction between blood and tissue creates the environment
      necessary for cell function. Analysis of physiology and pathophysiology of this
      system gives a unique perspective to the disease process, and provides the link
      between clinical and molecular medicine. The present status and future directions
      of this medical and scientific frontier were assessed and projected by experts in
      the field at a meeting in Italy in 1995, and the conclusions are presented in
      this article.

PMID- 9183303
TI  - Interrelationships between weight loss, body fat distribution and sex hormones in
      pre- and postmenopausal obese women.
AB  - OBJECTIVES: Relationships between regional body fat distribution and sex hormones
      as well as changes in sex hormones after weight loss were evaluated. SETTING: All
      subjects were hospitalized in the Institute of Internal Medicine of the
      University of Verona. SUBJECTS: Twenty-six premenopausal (age 33.7 +/- 10.2
      years) and 15 postmenopausal (age 57.9 +/- 5.9 years) obese women. INTERVENTIONS:
      Body weight, body-mass index, waist and hip circumferences, visceral fat by
      computed tomography and sex hormones were evaluated before and after 4 weeks on a
      very low energy diet. RESULTS: Body-mass index was higher in pre-than in
      postmenopausal women, although the difference was not significant. Total and free
      testosterone were significantly higher in the pre- than in the postmenopausal
      group (P < 0.001). Significant negative correlations were found between age and
      total testosterone (r = -0.65; P < 0.001), free testosterone (r = -0.54; P <
      0.001), androstenedione (r = -0.46; P < 0.01) and urinary cortisol excretion (r =
      -0.50; P < 0.01). A negative correlation was found between visceral fat and total
      testosterone (r = -0.41; P < 0.01). After adjusting for age, the negative
      correlation between total testosterone and visceral fat encountered both in the
      subject group as a whole and in premenopausal women was no longer significant,
      whilst a significant negative association between visceral fat and sex hormone
      binding globulin (SHBG) (r = -0.56; P < 0.001) was always found. When step-down
      regression analysis was used to evaluate the joint effect of age, menopausal
      status, and anthropometric and metabolic variables on sex hormones, age was the
      most powerful independent variable for predicting total testosterone, free
      testosterone and androstenedione levels, whilst menopausal status was the most
      powerful predictor of FSH and LH levels. Changes in hormones after VLED were
      analysed separately in pre- and postmenopausal women. None of the hormones
      changed significantly after VLED in the postmenopausal group, except for FSH
      values. LH, free testosterone and urinary cortisol excretion values decreased
      significantly after VLED in the premenopausal group. CONCLUSIONS: Our data show
      that age, to a greater extent than visceral fat, seems to be negatively
      associated with steroid sex hormones. Weight loss seems to be associated with
      changes in sex hormones only in premenopausal women.

PMID- 9183304
TI  - Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and
      responses to dietary change in Finnish adults.
AB  - OBJECTIVES: To analyse the association between the G/A polymorphism in the
      apolipoprotein A-1 (apo A-1) promoter region and plasma lipid levels, as well as
      their responses to dietary change, in Finnish adults. SUBJECTS AND DESIGN: Blood
      samples from 86 subjects (42 men. 44 women) who attended a dietary intervention
      study carried out in North Karelia in 1993 were available for the current
      analysis. The diet study consisted of a 2-week baseline period, followed by an 8
      week intervention period, and an 8-week switchback period. INTERVENTION: Diet was
      modified to a low-fat, low-cholesterol diet during the dietary intervention. MAIN
      OUTCOME MEASURES: Fasting plasma lipid, lipoprotein and apoliprotein levels were
      determined. RESULTS: At baseline, the high-density lipoprotein (HDL) cholesterol
      and apo A-1 levels were higher (P < 0.01) and the triglyceride levels were lower
      (P < 0.05) in men, but not in women, with the A allele. The differences in HDL
      cholesterol and apo A-1 levels between genotypes remained during the lowfat, low
      cholesterol diet and switchback periods. Apart from the difference between
      responses in apo A-1 during switchback to the original diet, lipid responses to
      dietary change did not differ significantly between genotypes. CONCLUSION: Our
      findings indicate a significant association between the apo A-1 promoter
      polymorphism and plasma apo A-1 and HDL-cholesterol in men. In theory, the higher
      plasma HDL-cholesterol and apo A-1 levels in the GA/AA group may confer some
      protection against coronary artery disease. The differences in HDL-cholesterol
      and apo A-1 levels between genotypes persisted during different diets suggesting
      that the possible benefit is independent of fat and cholesterol intake.

PMID- 9183305
TI  - The factor VR506Q mutation causing APC resistance is highly prevalent amongst
      unselected outpatients with clinically suspected deep venous thrombosis.
AB  - OBJECTIVE: Resistance to activated protein C (APC resistance), caused by a single
      point mutation in the factor V gene (FV:R506Q), is a major risk factor for venous
      thrombosis. As the significance of this mutation among unselected outpatients
      with deep-vein thrombosis (DVT) is not established, we have studied its
      prevalence among consecutive outpatients attending the emergency room due to a
      clinically suspected DVT. DESIGN, SETTING AND SUBJECTS: The FV:R506Q mutation was
      determined in 223 consecutive Swedish outpatients with clinically suspected DVT,
      and in 288 healthy controls. Using phlebography, the patients were classified as
      DVT-positive or DVT-negative. MAIN OUTCOME MEASURE: The prevalence of FV:R506Q
      mutation. RESULTS: The prevalence of the FV:R506Q mutation was 28% (28/99) in the
      DVT-positive subgroup (relative risk: 3.1; 95% CI: 1.7-5.5), and 23% (28/124) in
      the DVT negative subgroup (relative risk: 2.0; 95% CI: 1.1-3.6), as compared to
      11% (32/288) in the control group. In the DVT-positive subgroup, the FV:R506Q
      mutation was most common among younger patients with primary thrombosis (47%) and
      least common among older patients with secondary thrombosis (19%). The high
      prevalence of FV:R506Q mutation among DVT-negative patients was associated with a
      high frequency of previous venous thrombosis. Thus, 46% (13/28) of the DVT
      negative FV:R506Q carriers had a history of thrombosis, compared with only 22%
      (21/96) of the DVT-negative patients lacking the mutation (P = 0.01). CONCLUSION:
      To sum up, the FV:R506Q mutation is present in more than a quarter of Swedish DVT
      positive outpatients with clinically suspected DVT, indicating that APC
      resistance is a major thrombotic risk factor contributing to the high incidence
      of venous thrombosis in Sweden.

PMID- 9183306
TI  - Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis
      in the Helsinki Ageing Study.
AB  - OBJECTIVE: To examine the prevalence, underlying diseases, abnormalities of left
      ventricular function and prognosis in congestive heart failure (CHF) of old age.
      DESIGN: A population-based clinical and echocardiographic study with a 4-year
      mortality follow-up. SETTING: University hospital. SUBJECTS: Five hundred and one
      individuals born in 1904. 1909 and 1914 (367 women). MAIN OUTCOME MEASURES:
      Presence of CHF by clinical and chest radiograph criteria: left ventricular size
      and systolic function by echocardiography; grade of aortic and mitral valve
      lesion by Doppler echocardiography; 4-year total and cardiovascular mortality.
      RESULTS: Forty-one of 501 participants (8.2%) had CHF. Ischaemic heart disease
      (54%), hypertension (54%) and moderate-to-severe mitral or aortic valve disease
      (51%) were the main underlying conditions; 90% of patients had one or more of
      these diseases. Most individuals with CHF (28 of 39 patients, 72%) had normal
      left ventricular contractions at echocardiography. 'Diastolic CHF', defined as
      CHF with normal systolic left ventricular function and no regurgitant valve
      disease, was found in 51% (20 of 39 patients). The relative 4-year risk for death
      associated with CHF, adjusted for age and sex, was 2.1 (95% confidence interval
      1.3-3.4) for all-cause mortality and 4.2 (CI 1.9-5.6) for cardiovascular
      mortality. CONCLUSIONS: The prevalence of CHF in a population aged 75-86 years is
      approximately 8%. Ischaemic or valvular heart disease and hypertension are the
      main underlying conditions. At echocardiography, about 50% of the elderly with
      CHF have normal left ventricular systolic contractions in the absence of valve
      disease and an additional 20% have normal systolic function with mitral
      regurgitation. The presence of CHF doubles the age- and sex-adjusted risk of
      death from all causes, and quadruples the risk of cardiovascular death during 4
      year follow-up.

PMID- 9183308
TI  - Predictors of weight loss during treatment with d-fenfluramine.
AB  - OBJECTIVE: To identify parameters predictive of weight loss during treatment with
      d-fenfluramine. This may provide a tool to recognize patients who are sensitive
      to the weight-reducing effect of d-fenfluramine and thus prevent unnecessary
      prescription. DESIGN: An open intervention study during which biweekly control
      visits were scheduled. The study lasted 12 weeks. SETTING: The General Internal
      Medicine outpatient clinic of the Leiden University Hospital. Patients were
      recruited through a newspaper advertisement. SUBJECTS: Forty-eight healthy, obese
      patients (36 women and 12 men), aged 39 +/- 10 years (mean +/- SD) with a body
      mass index of 34.3 +/- 4.1 kg/m2 enrolled. INTERVENTIONS: d-Fenfluramine 15 mg
      twice daily for 12 weeks. MAIN OUTCOME MEASURES: Body weight, height, waist and
      hip circumference, food intake, smoking habits, obesity history, treatment
      history, family history of obesity and compliance with the medication scheme were
      recorded as potential predictors of weight loss. RESULTS: One patient was
      withdrawn because of depressive symptoms. Thirteen patients did not lose weight.
      On average, the other 34 patients lost 5.7 +/- 2.9 kg or 18.1 +/- 9.4% of excess
      body weight. High compliance with the drug regimen was associated with a twofold
      greater weight loss (17.7 +/- 12.3 vs. 9.0 +/- 9.4% of excess weight, ANOVA, P =
      0.0088). Patients with a positive family history of obesity lost twice as much
      weight as patients without obese relatives (15.8 +/- 11.8 vs. 6.0 +/- 7.3% of
      excess weight; ANOVA, P = 0.0078). No other potential determinants were
      predictive for weight loss. CONCLUSIONS: Informing patients that compliance with
      the medication scheme improves treatment outcome will be useful. Previous
      failures to lose weight should not exclude patients from treatment. A positive
      family history of obesity needs further evaluation as a possible determinant of
      weight loss in forthcoming studies.

PMID- 9183307
TI  - Haemophilia prophylaxis in young patients--a long-term follow-up.
AB  - OBJECTIVES: To review long-term prophylactic factor treatment in young patients
      with severe haemophilia A and B, focusing on the orthopaedic and radiological
      outcome. DESIGN: We received 34 patients with severe haemophilia A (n = 29) and B
      (n = 5), aged 7-22 years. Age at start of treatment was 1-4.5 years. Dosages of
      factor concentrate (F VIII and F IX, respectively) were 25-40 IU/kg body weight,
      three times a week for haemophilia A and twice a week for haemophilia B. The
      patients had been checked annually over a 5-year period (1990-95). Orthopaedic
      and radiological joint scores were evaluated according to recommendations by the
      World Federation of Haemophilia. SETTING: All results were obtained at the
      Department for Coagulation Disorders, University of Lund, Malmo University
      Hospital, Malmo, Sweden. RESULTS: Orthopaedic and radiological joint scores were
      found to have remained unchanged during follow-up in almost all patients and to
      be still zero (i.e. no unaffected joints) in 79% (n = 27) of the patients.
      CONCLUSION: There is a growing international consensus haemophilic arthropathy
      can be prevented by administering early high-dose prophylaxis. The results of the
      present investigation strongly support this opinion.

PMID- 9183309
TI  - Identifying individuals with high fat levels and low P:S ratios, in their diets,
      for intensive dietary intervention.
AB  - OBJECTIVES: To assess whether simple scores from a dietary questionnaire could
      identify those with high dietary fat or low P:S ratio intakes, for intensive
      dietary intervention. DESIGN: Cross-sectional and longitudinal studies. SETTING:
      Community setting in the Hunter Region of New South Wales, Australia. SUBJECTS:
      Two random samples of adults 35-69 years from the electoral roll. In the cross
      sectional study 287/322 (86%) subjects completed the diet questionnaire and a
      reference standard questionnaire. In the longitudinal study 546/653 (84%) of
      subjects completed the diet questionnaire, and had blood cholesterol measured on
      two occasions, 3 months apart. MAIN OUTCOME MEASURES: In the cross-sectional
      study, the simple scores of total fat intake (Fat Intake Score) and P:S ratio
      (Unsaturated Score) were compared with the daily intakes of total fat and P:S
      ratio obtained from the standard questionnaire. In the longitudinal study,
      changes in the scores were compared with changes in blood total cholesterol.
      RESULTS: A Fat Intake Score of greater than 125 had the best receiver operator
      characteristics for identifying high total fat intake (> 100 g/day: sensitivity =
      67%, specificity = 70%). An Unsaturated Score of less than 0.3 had the best
      characteristics for identifying a low P:S ratio (< 0.5: sensitivity = 63%,
      specificity = 60%). Subjects who decreased Fat Intake Score by one category, had
      a fall in blood cholesterol of 0.14 mmol L-1 (95% confidence interval (CI) = 0.01
      0.26 mmol L-1), while those decreasing by two categories decreased their blood
      cholesterol by 0.56 mmol L-1 (95% CI = 0.30-0.86 mmol L-1). Subjects increasing
      their Unsaturated Score category had a fall in blood cholesterol of 0.17 mmol L-1
      (95% CI = 0.02-0.32 mmol L-1). CONCLUSION: Simple dietary scores can identify
      those with high fat intakes, and monitor changes related to changes in blood
      cholesterol levels.

PMID- 9183310
TI  - Do drug costs affect physicians' prescription decisions?
AB  - OBJECTIVE: To study the impact of the cost of pharmaceuticals on physicians'
      decisions about drug prescription. DESIGN: A simulation protocol for the
      treatment of two patients, one with mild and the other with a severe form of
      urinary tract infection (UTI), was designed. Thirty family physicians in
      outpatient clinics and 30 physicians in the internal medicine wards of a
      Community Hospital participated in the project. They had to prescribe treatment
      for the patients twice: at phase I, when the drug cost was unknown, and at phase
      II, after 2 months, when the price of the drugs was brought to their attention.
      The physicians selected the medication from a list of drugs commonly used for the
      treatment of UTIs. RESULTS: Analysis of the findings indicates that an awareness
      of drug costs affects prescription decisions among physicians in hospital wards,
      whereas family physicians showed a preference for less expensive drugs even
      before they were informed about drug costs. An extrapolation of the results shows
      that knowledge about the cost of the drugs usually administered for treatment of
      UTI, could save at least IS 112,883 ($34,207) a month to Kupat Holim Klalit (KHK)
      the health insurance institution to which the outpatient clinics and the hospital
      belong. CONCLUSIONS: When economic aspects of healthcare are considered,
      information on drug costs may be an important factor in physicians' decision
      making processes and for saving pharmaceutical expenses.

PMID- 9183311
TI  - Do-not-resuscitate orders--should the patient be informed?
AB  - OBJECTIVES: To analyse the ethical implications of informing patients about their
      do-not-resuscitate status (DNR). DESIGN: Questionnaire. SETTING: Nationwide, 6
      months after the publication of guidelines on DNR in 1994. SUBJECTS: A 10% random
      sample of the members of the Swedish Cardiac Society. 104 physicians and 196
      nurses. MAIN OUTCOME MEASURES: To what extent are patients, physicians and nurses
      involved in decisions about DNR, and how should the ethical conflict involved in
      informing patients about their DNR status be described and analysed? RESULTS: Of
      73% responding, 84% of the physicians and 8% of the nurses had made a DNR
      decision. The decision was regarded as ethically right and well timed and it was
      discussed with 33% of the competent patients. Half of the respondents believed
      that DNR orders should be discussed with the competent patient. but still only
      one third of the patients are involved. The ethical conflict is analysed using
      the principles of autonomy and nonmaleficence as value premises. CONCLUSIONS:
      Many physicians are still reluctant to find out what the patient wants. Being
      ignorant they risk harming the patient. It is recommended that information about
      DNR status should be given incrementally and that the attitudes of the old and
      chronically ill in-hospital patients are studied. Do they want to be informed,
      and if so, how and when do they want it to be done?

PMID- 9183312
TI  - Prevalence of activated protein C resistance and analysis of clinical profile in
      thromboembolic patients. A Belgian prospective study.
AB  - OBJECTIVES: To assess the prevalence of activated protein C resistance (APC-R)
      among healthy subjects and thromboembolic patients and to determine the clinical
      characteristics associated with APC-R. DESIGN: A prospective study. SETTING: One
      academic medical centre. SUBJECTS: 91 health controls and 126 thromboembolic
      patients. MEASUREMENTS: Patients and control were genotyped for the factor V
      Leiden (VaQ506) mutation. The anticoagulant response of the patient's plasma to
      activated protein C was also determined. RESULTS: The frequency of APC-R was 3.3%
      among healthy control subjects and 22% among thrombotic patients of whom 18% were
      heterozygous and 4% were homozygous. The mean age at the first thrombotic event
      and the severity of thrombotic disease including the proportion of proximal deep
      vein thrombosis and the frequency of lung embolism were identical among APC-R
      positive and negative patients. A family history of thromboembolic disease was
      elicited more frequently in APC-R positive than in APC-R negative patients (57%
      vs. 22%, P < 0.001). The recurrence rate was higher for APCR-R positive patients
      (57% vs. 34%, P < 0.05). The percentage of cases with a factor predisposing to
      thrombosis was very similar in APC-R positive (57%) and negative (68%) patients.
      CONCLUSIONS: A familial history of thromboembolic disease and recurrences are
      significantly more frequent among APC-R positive than APC-R negative patients.

PMID- 9183314
TI  - Severe community-acquired pneumonia, shock and multiorgan dysfunction syndrome
      caused by Chlamydia pneumoniae.
AB  - Chlamydia pneumoniae has been increasingly recognized as an important
      aetiological agent in community-acquired pneumonia. A case of severe community
      acquired pneumonia and multifunction dysfunction syndrome resulting from
      Chlamydia pneunoniae infection in a previously healthy adult is presented.

PMID- 9183313
TI  - Paracetamol-induced cholestatic and granulomatous liver injuries.
AB  - OBJECTIVE: To describe uncommon (previously unreported) types of adverse liver
      reactions to paracetamol. DESIGN: In addition to describing patients, with
      uncommon types of liver reactions to paracetamol, admitted to our hospitals, we
      surveyed all the liver reactions to paracetamol reported to the Swedish Adverse
      Drug Reactions Advisory Committee from 1973 to 1993. SETTING: The Swedish
      population of 8 million inhabitants. MEASUREMENT: Extensive medical evaluation.
      RESULTS: We found one case with a cholestatic liver reaction and one with
      granulomatous hepatitis. The reactions were probably idiosyncratic and took
      several months to disappear. CONCLUSION: In addition to the well-known dose
      related toxic liver damage paracetamol may rarely cause non-dose-related severe,
      prolonged cholestasis or granulomatous hepatitis with cirrhosis.

PMID- 9183315
TI  - Exercise vs dietary change to bring about weight loss.

PMID- 9183316
TI  - More on predicting dietary phosphorus intake.

PMID- 9183317
TI  - Lactation consulting: is it for you?

PMID- 9183318
TI  - Scientific underpinnings for the profession: dietitians in research.

PMID- 9183319
TI  - Psychosocial concerns and weight control behaviors among overweight and
      nonoverweight Native American adolescents.
AB  - OBJECTIVE: To compare the psychosocial and weight-related concerns and weight
      control, eating, and exercise behaviors of overweight and nonoverweight Native
      American adolescents living on or near reservations. STUDY DESIGN: A cross
      sectional survey assessed psychosocial, health, and weight-specific concerns;
      disordered eating; and health-promoting behaviors. STUDY POPULATION: The study
      population included 11,868 Native American youth in grades 7 through 12.
      STATISTICAL ANALYSES PERFORMED: Analyses of variance and chi 2 tests were used to
      examine associations between weight status and psychosocial and weight-related
      concerns and behaviors. Stratified analyses were done by gender and by gender and
      age. RESULTS: Self-reported weights and heights indicated that 25% of the study
      population was overweight. Overweight youth were twice as likely to report health
      concerns as nonoverweight youth. Although a high percentage of nonoverweight
      youth expressed body- or weight-related concerns and reported engaging in
      disordered eating behaviors, prevalence rates for these concerns were
      significantly higher among overweight youth. Overweight youth were also somewhat
      less likely to engage in health-promoting behaviors. In contrast, differences in
      global psychosocial concerns were minimal. APPLICATIONS: Overweight Native
      American youth were concerned about their weight, but did not appear to have
      major psychosocial concerns associated with being overweight. Interventions aimed
      at obesity prevention and overall health promotion are essential, given the high
      prevalence of obesity and of psychosocial and weight-related concerns and
      behaviors among the study population as a whole. The challenge is to develop
      culturally appropriate interventions aimed at the promotion of healthful weight
      control behaviors that will not lead to negative psychosocial consequences.

PMID- 9183320
TI  - Decreased fat and nitrogen losses in patients with AIDS receiving medium-chain
      triglyceride-enriched formula vs those receiving long-chain-triglyceride
      containing formula.
AB  - OBJECTIVE: The purpose of this study was to compare two enteral formulas,
      differing only in fat source, for product acceptance, tolerance, and effect on
      fat malabsorption and nutritional status in subjects with acquired immune
      deficiency syndrome (AIDS). DESIGN: The double-blind, randomized 15-day trial was
      divided into a 3-day period in which solid food was consumed followed by a 12-day
      experimental period in which liquid formulas were consumed. SETTING/SUBJECTS:
      Twenty-three men and one woman with AIDS and fat malabsorption completed the
      study. The study was conducted in the General Clinical Research Center,
      University of Alabama Hospital, University of Alabama at Birmingham. Laboratory
      assays were performed in the Department of Nutrition Sciences. INTERVENTIONS:
      After 3 days of consuming a controlled, solid food diet containing 100 g fat per
      day from mixed sources to document fat malabsorption, subjects were randomly
      assigned to one of two groups. Each group received a liquid formula containing
      35% of energy as fat for 12 days. One group received a formula containing 85%
      medium-chain triglycerides (MCTs) and the control group received a formula
      containing 100% long-chain triglycerides. MAIN OUTCOME MEASURES: Determinations
      included stool number, consistency, weight, and fat and nitrogen content; urine
      nitrogen and creatinine levels; and body weight. STATISTICAL ANALYSIS PERFORMED:
      Subject demographic and other baseline characteristics were compared using two
      sample t tests; stool and urine assessments were compared between groups at the
      initial experimental period using two-sample t tests; changes from initial to
      final experimental periods were assessed by means of analysis of covariance;
      changes in pooled intake, body weight, and the number and consistency of bowel
      movements were also assessed using analysis of covariance. All statistical tests
      were two-tailed and considered significant at P < .05. RESULTS: Within-group
      comparisons indicated that subjects fed the MCT formula showed significantly
      decreased stool fat and stool nitrogen content (P = .01 and P = .03,
      respectively) and increased fat absorption (P = .03), whereas those fed the
      control formula did not. Differences in stool fat between the groups were not
      statistically significant. However, the difference in fat absorption from the
      initial to final formula period was significant (P = .04). Subjects consuming the
      MCT formula also tended to have a decreased number of bowel movements and
      abdominal symptoms, whereas subjects fed the control formula showed no
      improvement. All subjects maintained their body weights. APPLICATIONS: There may
      be advantages to using an MCT-based formula in the treatment of AIDS-associated
      malabsorption.

PMID- 9183321
TI  - Wheat starch intolerance in patients with celiac disease.
AB  - OBJECTIVE: Evaluate in patients with celiac disease the tolerance of prolonged
      consumption of small amounts of gliadin contained in products containing wheat
      starch. DESIGN: Open 1-year trial of the addition of wheat starch to a gluten
      free diet in a cohort of adult patients with biopsy-proven celiac disease who had
      never consumed wheat starch. The control group consisted of patients with celiac
      disease who tolerated wheat starch. SUBJECTS: Seventeen patients with celiac
      disease and 14 control patients, all diagnosed according to criteria of the
      European Society of Pediatric Gastroenterology and Nutrition, were recruited from
      the Canadian Celiac Association and the Quebec Celiac Foundation. SETTING: The
      study was conducted in the outpatient clinic of the Gastroenterology and
      Nutrition Service of Ste Justine Hospital, Montreal, Quebec, Canada.
      INTERVENTIONS: Patients were asked to consume four to six portions daily of a
      wheat starch-containing product, mainly bread, for up to 1 year. MAIN OUTCOME
      MEASURES: The gliadin content of the wheat starch product used in this trial was
      quantified by enzyme-linked immunosorbent assay. Patient outcome measures
      included symptoms, nutritional parameters (anthropometric data, complete blood
      count, serum folate and iron levels), and immunologic parameters (antigliadin
      antibody and antiendomysium antibody titers). RESULTS: A quantifiable amount of
      immunoreactive gliadin (0.75 mg/100 g) was found in the wheat starch. The
      majority of the patients with celiac disease (11 of 17) who had never consumed
      wheat starch previously developed symptoms, which resolved within weeks of
      discontinuing the product. Relapse of skin lesions was seen in two of three
      patients with coexisting dermatitis herpetiformis. No weight loss or biochemical
      changes were observed. Despite the presence of symptoms, antigliadin antibody and
      antiendomysium antibody determinations were not useful to detect the clinical
      intolerance. APPLICATIONS: The innocuousness of the long-term ingestion of
      "gluten-free" products containing wheat starch is still unproven, and prolonged
      use of such products by patients with celiac disease cannot be recommended.

PMID- 9183322
TI  - Food safety training needs exist for staff and consumers in a variety of
      community-based homes for people with developmental disabilities.
AB  - OBJECTIVE: To determine staff and consumer-focused food safety training needs in
      community-based homes for people with developmental disabilities as well as
      dietitians' perceptions of food-handling practices in these homes. DESIGN: Direct
      care staff and dietitians were surveyed according to a modified Dillman method
      using a mailed, self-administered questionnaire. Main outcome measures included
      food-handling knowledge, attitudes, and practices of staff and consumers as
      reported by staff and dietitians; critical control points in safe food
      preparation in the homes based on the Hazard Analysis and Critical Control Point
      system; and learning preferences of staff and consumers. SUBJECTS: A 10%
      probability sample of direct-care staff in homes for people with developmental
      disabilities in western Massachusetts and a nonprobability sample of dietitians
      who work with this population were surveyed. Results are reported from 132 and 18
      respondents, respectively. STATISTICAL ANALYSES PERFORMED: Descriptive
      statistics, chi 2 statistic, and the Fisher's exact test. RESULTS: Staff
      knowledge of safe food preparation is lacking in several areas, including storage
      and handling procedures. Although staff and consumers do not always follow safe
      food-handling practices, the staff reported that they follow recommended food
      handling practices more often than the dietitians reported they do. Most staff
      and dietitians reported that staff and consumers had never attended a food safety
      training program, but that all of the critical control points surveyed would be
      somewhat helpful if they were included in a food safety workshop. APPLICATIONS: A
      food safety training program would be beneficial for staff and consumers.
      Programs should be geared to staff and include ideas and materials for consumers.
      Consumer modules could then be adapted to individual learning levels by direct
      care staff in the homes. The Safe Food at Home workshop was developed on the
      basis of the results of this study and incorporates the approaches described in
      this article.

PMID- 9183323
TI  - Practice points: translating research into practice. Attention to food safety
      should not wait for a crisis.

PMID- 9183324
TI  - Analysis of the decision to select a conventional or cook-chill system for
      hospital foodservice.
AB  - OBJECTIVE: The objectives of this study were to determine what variables hospital
      foodservice directors consider when selecting a conventional or cook-chill
      system, to determine the importance of each variable considered, and to compare
      decision variables by type of foodservice system. DESIGN: Survey questionnaire.
      SUBJECTS/SETTING: Hospital foodservice directors in general, medical-surgical
      hospitals who had been involved in the decision to select a conventional or cook
      chill system (N = 127). STATISTICAL ANALYSIS: Analysis of variance and chi 2.
      RESULTS: The decision process used by foodservice directors who selected a
      conventional system appears to differ significantly from the process used by
      directors who selected cook-chill systems. However, directors in this study who
      selected a cook-chill system were more likely than those who selected
      conventional systems to consider more issues in the decision process, visit other
      operations, place more importance on return on investment and projected labor
      costs, calculate more values, consider both conventional and cook-chill options,
      and use nonfoodservice personnel such as manufactures' representatives and
      consultants. APPLICATIONS: Results of this research suggest that the decision
      process to select a foodservice system in hospitals is complex and is one that
      foodservice directors will likely be involved in several times throughout their
      careers. Directors who have made such decisions appear to consider many issues,
      both quantitative and qualitative, when selecting either a conventional or cook
      chill system. Regardless of the system chosen, directors indicated that numerous
      issues were important in the decision.

PMID- 9183325
TI  - Nutrition, exercise, and healthy aging.
AB  - Advancing age is associated with a remarkable number of changes in body
      composition, including reduction in lean body mass and increase in body fat,
      which have been well documented. Decreased lean body mass occurs primarily as a
      result of losses in skeletal muscle mass. This age-related loss in muscle mass
      has been termed "sarcopenia". Loss in muscle mass accounts for the age-associated
      decreases in basal metabolic rate, muscle strength, and activity levels, which,
      in turn are the cause of the decreased energy requirements of the elderly. In
      sedentary persons, the main determinant of energy expenditure is fat-free mass,
      which declines by about 15% between the third and eighth decade of life. It also
      appears that declining energy needs are not matched by an appropriate decline in
      energy intake, with the ultimate result being increased body fat content.
      Increased body fatness and increased abdominal obesity are thought to be directly
      linked to the greatly increased incidence of non-insulin-dependent diabetes
      mellitus among the elderly. In this review we will discuss the extent to which
      regularly performed exercise can affect nutrition needs and functional capacity
      in the elderly. We will also discuss a variety of concerns when prescribing
      exercise in the elderly, such as planning for a wide variability in functional
      status, medical status, and training intensity and duration. Finally, we will
      attempt to provide some basic guidelines for beginning an exercise program for
      older men and women and establishing community-based programs.

PMID- 9183326
TI  - Essential nature of choline with implications for total parenteral nutrition.
AB  - Choline is known to be important in many metabolic pathways; at this time,
      however, it is not considered an essential nutrient for human beings. Current
      evidence strongly suggests that choline is "conditionally essential,"
      particularly for patients receiving total parenteral nutrition (TPN). Studies in
      patients receiving long-term TPN have shown that low levels of plasma choline are
      common and can be associated with hepatic steatosis. Treatment of these patients
      with oral administration of choline improved plasma levels and decreased hepatic
      fat content; however, oral choline supplements are associated with poor
      compliance. More recently, investigators have evaluated intravenous
      administration of choline as a treatment for TPN-associated hepatic steatosis in
      patients with documented subnormal plasma free-choline levels. Initial results
      indicate that intravenous administration of choline may be an effective treatment
      for TPN-associated hepatic dysfunction.

PMID- 9183327
TI  - Nutritional aspects of cancer-related fatigue.
AB  - Fatigue, which may well be the most common experience of patients with cancer,
      remains underappreciated by health care professionals. Perhaps one reason is that
      because of its complexity and many components, fatigue is not completely
      understood. Knowledge of fatigue models, such as the integrated Fatigue Model of
      Piper, can help dietitians identify potential causes of fatigue such as activity
      rest patterns, and identification can lead dietitians to early intervention.
      Understanding cancer treatment factors, such as nausea and decreased
      participation in activities of daily living, that are believed to play a part in
      fatigue form another level on which dietitians can provide intervention. Through
      intervention, dietitians, working with patients and other members of the
      multidisciplinary team, may increase the understanding and appreciation of
      fatigue as well as provide relief from it. Efforts to maintain nutritional status
      can decrease or prevent some of the fatigue associated with cancer and its
      treatment. Therefore, the goal of clinical dietitians who work with a fatigued
      patient with cancer is to use nutrition management to minimize therapeutic side
      effects and maximize the patient's nutritional parameters.

PMID- 9183328
TI  - Dietary intake and plasma concentrations of vitamin E, vitamin C, and beta
      carotene in patients with coronary artery disease.

PMID- 9183329
TI  - The effect of color on perceived flavor intensity and acceptance of foods by
      young adults and elderly adults.

PMID- 9183330
TI  - Increased iron content of food due to stainless steel cookware.

PMID- 9183331
TI  - Position of the American Dietetic Association: promotion of breast-feeding.

PMID- 9183332
TI  - Standards of practice criteria for clinical nutrition managers.

PMID- 9183333
TI  - Relationship between prothrombin activation fragment F1.2 and international
      normalized ratio in patients with atrial fibrillation. Stroke Prevention in
      Atrial Fibrillation Investigators.
AB  - BACKGROUND AND PURPOSE: The prothrombin time (expressed as the international
      normalized ratio [INR]) is the standard method of monitoring warfarin therapy in
      patients with atrial fibrillation. Prothrombin activation fragment F1.2 provides
      an index of in vivo thrombin generation and might provide a better index of the
      effective intensity of anticoagulation. We examined the relationship between F1.2
      and INR in patients with atrial fibrillation. METHODS: We measured INR and F1.2
      levels in 846 patients with atrial fibrillation participating in the Stroke
      Prevention in Atrial Fibrillation III study. Two hundred nineteen (26%) were
      taking aspirin alone, 326 (39%) were taking adjusted-dose warfarin, and 301 (36%)
      were taking a low fixed dose of warfarin (1 to 3 mg) plus aspirin (combination
      therapy). F1.2 levels were measured with an enzyme-linked immunosorbent assay.
      RESULTS: Patients receiving adjusted-dose warfarin or combination therapy had
      significantly higher INR and significantly lower F1.2 values than those on
      aspirin alone (P < or = .0001 for each of the four comparisons). F1.2 values
      (nanomolar) were inversely correlated with INR (F1.2 = -0.1 + 2.3[1/INR]; R2 =
      .37; P < .0001; simple linear regression). However, significant variability
      remained. Among patients receiving warfarin, older patients had higher F1.2
      values than younger patients after adjustment for INR intensity (P < .001) in the
      model. There was no difference in the relationship between F1.2 and INR between
      men and women. CONCLUSIONS: Increasing intensity of anticoagulation, as measured
      by the INR, is associated with decreasing thrombin generation as measured by the
      F1.2 level, but significant variability exists in this relationship. Older
      anticoagulated patients have higher F1.2 values than younger patients at
      equivalent INR values. The clinical significance of these differences is not
      clear. F1.2 measurement might provide information regarding anticoagulation
      intensity in addition to that reflected by the INR.

PMID- 9183334
TI  - Ischemic cerebral infarction after rt-PA and heparin therapy for acute myocardial
      infarction. The TIMI-II pilot and randomized clinical trial combined experience.
AB  - BACKGROUND AND PURPOSE: Ischemic cerebral infarction (CI) is a serious
      complication of acute myocardial infarction (MI). Little information exists on CI
      after thrombolytic therapy for MI. METHODS: Of 3924 MI patients treated with
      recombinant tissue plasminogen activator (rt-PA) and heparin, 29 (0.7%) developed
      CI after treatment. All CI patients had detailed neurological evaluations, and 27
      (93%) had CT scans centrally reviewed. RESULTS: Age range was 40 to 74 years
      (mean, 60 years); 25 patients (86%) were men, and 22 (76%) were white. The
      electrocardiographic location of MI was anterior in 22 (76%) and nonanterior in 7
      (24%). Five CIs occurred within 6 hours, 4 between 6 to 24 hours, 8 during the
      remainder of the first week, 10 during the second week, and 2 others distributed
      over the 4 weeks after study entry. Six of 29 CIs did not involve the cerebral
      cortex; 9 patients (31%) had multiple CIs. Of 28 CIs thought to be embolic in
      origin, 17 showed strong evidence for at least one cardiac abnormality (mural
      clot, wall-motion abnormality, aneurysm, or atrial fibrillation) known to be
      associated more specifically with embolism than MI. Eight of 27 CIs (30%) with CT
      scans had hemorrhagic transformation of varying degrees; 5 were symptomatic.
      CONCLUSIONS: The time of occurrence and sites of CI after rt-PA and heparin
      therapy for acute MI are similar to those reported during the prethrombolytic
      era.

PMID- 9183335
TI  - Intra-arterial nitrovasodilators do not increase cerebral blood flow in
      angiographically normal territories of arteriovenous malformation patients.
AB  - BACKGROUND AND PURPOSE: The mechanism of adaptation to chronic cerebral
      hypotension in normal brain adjacent to cerebral arteriovenous malformations
      (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow
      (CBF) studies in structurally and functionally normal vascular territories during
      53 distal cerebral angiographic procedures in 37 patients with AVMs. METHODS: CBF
      was measured using the superselective intra-arterial 133Xe method before and
      after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine
      (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n =
      16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). RESULTS: Mean +/- SD
      systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range,
      20 to 97 mm Hg) pressures were not different among groups. Verapamil increased
      CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of
      acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or
      nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside
      decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent
      change in CBF after drug administration was proportional to cerebral arterial
      pressure for verapamil only (r = .57, P = .0051). CONCLUSIONS: When infused intra
      arterially in clinically relevant doses in both hypotensive and normotensive
      normal vascular territories remote from an AVM nidus, calcium channel blockade
      caused vasodilation, but there was an absence of response to nitric oxide
      mediated vasodilators. These data suggest that (1) the nitric oxide pathway
      probably is not involved in the adaptation to chronic cerebral hypotension in AVM
      patients and (2) if our findings in vessels remote from or contralateral to the
      AVM are applicable to vessels of patients with other forms of cerebrovascular
      disease, clinically relevant doses of intra-arterial nitrovasodilators may not be
      useful in the manipulation of cerebrovascular resistance.

PMID- 9183336
TI  - Psychosocial stressors in patients with major depression and silent cerebral
      infarction.
AB  - BACKGROUND AND PURPOSE: We previously found that silent cerebral infarction (SCI)
      was present in most of the patients older than 50 years with major depression who
      were examined. The present study was designed to clarify the relationship between
      psychosocial stressors and SCI in patients with major depression. METHODS: Forty
      two patients with unipolar depression underwent MRI and were classified as SCI
      negative (n = 19) or SCI-positive (n = 23). The SCI-positive group was
      subclassified into those with moderate SCI (n = 16) and those with severe SCI (n
      = 7). The relationship between the patients' DSM-III-R axis IV scores and SCI was
      evaluated. RESULTS: The axis IV score was significantly lower in the SCI-positive
      group than in the SCI-negative group (P < .05). Within the SCI-positive group,
      the mean axis IV score was significantly lower in those with severe SCI than in
      those with moderate SCI (P < .05). CONCLUSIONS: Our findings suggest that
      depression in patients with SCI involves more neurological factors than
      psychosocial stressors.

PMID- 9183337
TI  - Poststroke depression among the Chinese elderly in a rural community.
AB  - BACKGROUND AND PURPOSE: A door-to-door survey was conducted in two townships in
      the Kinmen islets to investigate the prevalence and other characteristics related
      to depressive disorders of stroke survivors in an elderly Chinese population.
      METHODS: Our target population comprised the registered residents > or = 65 years
      old (n = 2056) of a total population of 26 105 on August 1, 1993. All
      participants answered a questionnaire, filled in a Geriatric Depression Scale
      short form (GDS-S), and received a neurological examination. Depression was
      defined as a GDS-S score > or = 5. RESULTS: Twenty-eight of 45 stroke survivors
      (62.2%) and 491 of 1471 nonstroke subjects (33.4%) were classified as depressed.
      The frequency of stroke survivors' depressive disorders was significantly higher
      that of nonstroke subjects (P < .001). Multiple regression analysis indicated
      that GDS-S scores were most related with the activities of daily living (R2 =
      .19, P = .004) in the stroke survivors. CONCLUSIONS: Depressed mood was common
      after stroke, and activities of daily living were an important factor for
      depression in stroke survivors in the community.

PMID- 9183338
TI  - Cerebral vascular malformations adjacent to sensorimotor and visual cortex.
      Functional magnetic resonance imaging studies before and after therapeutic
      intervention.
AB  - BACKGROUND AND PURPOSE: It is not known how cerebral vascular malformations
      affect the function of the surrounding brain. Functional magnetic resonance
      imaging (fMRI) can provide information about normal functional neuroanatomy and
      its alteration by vascular lesions and therapeutic intervention. METHODS: We
      performed fMRI studies in 24 patients harboring vascular malformations adjacent
      to primary somatosensory, motor, and visual cortex. The fMRI studies consisted of
      the acquisition of an image time series coupled with functional activation of
      motor, sensory, or visual cortex in both hemispheres. Activated voxels were
      identified using frequency domain analyses, and their number and anatomic
      location were compared between the affected and unaffected hemispheres. RESULTS:
      Every patient capable of performing the desired task showed functional
      activation. Eight patients without neurological deficits showed a symmetrical
      pattern of activation between the hemispheres. Each had a vascular malformation
      located one or more gyri from the functional region imaged. Three patients showed
      hemispheric symmetry in the location of activated cortex but with a marked
      asymmetry in the number of activated voxels. Each harbored vascular malformations
      located within one gyrus of the functional region and showed either subtle or no
      neurological deficit. Eleven patients showed hemispheric asymmetry in the
      location of activated cortex. In 6, the anatomic displacement appeared to be due
      to a mass effect of the lesion. In 5, the activation occurred at a different
      anatomic locale, and the patients exhibited gross neurological deficit in the
      respective function. Posttherapeutic changes in functional activation reflected
      elimination of the mass effect or recovery of clinical function. CONCLUSIONS:
      Systematic fMRI studies are possible in patients with vascular malformations in
      brain regions adjacent to primary somatosensory, motor, and visual cortex.
      Displacement of the activated region and hemispheric asymmetry in the number of
      activated voxels in the functional regions appear to reflect the anatomic and
      physiological impact of the vascular malformation. Changes in fMRI findings after
      intervention reflect the consequences of therapy and parallel clinical recovery.

PMID- 9183339
TI  - Acute stroke care and rehabilitation: an analysis of the direct cost and its
      clinical and social determinants. The Copenhagen Stroke Study.
AB  - BACKGROUND AND PURPOSE: Stroke represents a major economic challenge to society.
      The direct cost of stroke is largely determined by the duration of hospital stay,
      but internationally applicable estimates of the direct cost of acute stroke care
      and rehabilitation on cost-efficient stroke units are not available. Information
      regarding social and medical factors influencing the length of hospital stay
      (LOHS) and thereby cost is needed to direct cost-reducing efforts. METHODS: We
      determined the direct cost of stroke in the prospective, consecutive, and
      community-based stroke population of the Copenhagen Stroke Study by measuring the
      total LOHS in the 1197 acute stroke patients included in the study. All patients
      had all their acute care and rehabilitation on a dedicated stroke unit.
      Neurological impairment was measured by the Scandinavian Stroke Scale. Local
      nonmedical factors affecting the LOHS, such as waiting time for discharge to a
      nursing home after completed rehabilitation, were accounted for in the analysis.
      The influence of social and medical factors on the LOHS was analyzed in a
      multiple linear regression model. RESULTS: The average LOHS was 27.1 days (SD,
      44.1; range, 1 to 193), corresponding to a direct cost of $12.150 per patient
      including all acute care and rehabilitation. The LOHS increased with increasing
      stroke severity (6 days per 10-point increase in severity; P < .0001) and single
      marital status (3.4 days; P = .02). Death reduced LOHS (22.0 days; P < .0001).
      Age, sex, diabetes, hypertension, claudication, ischemic heart disease, atrial
      fibrillation, former stroke, other disabling comorbidity, smoking, daily alcohol
      consumption, and the type of stroke (hemorrhage/infarct) had no independent
      influence on LOHS. CONCLUSIONS: Acute care and rehabilitation of unselected
      patients on a dedicated stroke unit takes on average 4 weeks. In general,
      comorbidity such as diabetes or heart disease does not increase LOHS. Efforts to
      reduce costs should therefore aim at reducing initial stroke severity or
      improving the rate of recovery.

PMID- 9183340
TI  - Epidemiology and costs of acute hospital care for cerebrovascular disease in
      diabetic and nondiabetic populations.
AB  - BACKGROUND AND PURPOSE: Little is known about the pattern of cerebrovascular
      disease (CVD) for diabetic and nondiabetic patients or about the cost of
      treatment for CVD in the United Kingdom. The purpose of this study was to extend
      previous work to describe the epidemiology and cost of acute care of CVD as a
      frequent comorbidity of diabetes in a UK population (408 000 people). METHODS:
      Routine data describing inpatient care for a 4-year period were analyzed
      (financial years 1991/1992 to 1994/1995). These data had undergone record linkage
      to draw together records from the same patients. Cost estimates were determined
      by attributing a diagnosis-related group cost weight to each record. Mortality
      data from an overlapping period were supplied by the Office of Population
      Censuses and Surveys. RESULTS: There were 11 196 CVD admissions (3.1% of all
      admissions). Of these, 7351 (66%) were primary diagnoses. These admissions were
      generated by 5358 patients (3904 primary diagnosis). For people with diabetes,
      the incidence rate was between 23 and 32.8 per 1000 per year compared with 2.4 to
      3.3 per 1000 for the population as a whole, depending on the use of primary and
      subsidiary codes. The age-adjusted relative risk of stroke in diabetic men versus
      nondiabetic men was 3.70 (95% confidence interval, 3.53 to 3.88) and in women was
      4.35 (95% confidence interval, 4.37 to 4.76). We describe other epidemiological
      relationships. The cost of CVD is between pounds 1.1 and pounds 1.6 million per
      100 000 population-at least pounds 0.7 million per 100 000 for CVD alone.
      Approximately 15% of this value is related to diabetes, and an estimated 94% of
      this diabetes-related expenditure is potentially avoidable. CONCLUSIONS: CVD
      represents a major source of expenditure for health services, and diabetes is
      confirmed as a major risk factor within this disease group. Differences between
      diabetic and nondiabetic inpatient patterns of CVD may reflect greater incidence
      of comorbidities in the former.

PMID- 9183341
TI  - Relationship between insulin and carotid atherosclerosis in the general
      population. The Bruneck Study.
AB  - BACKGROUND AND PURPOSE: Although several studies have investigated the
      association between insulin and coronary heart disease, the relationship between
      this hormone and carotid atherosclerosis is not well established. METHODS: As a
      part of a population-based survey on atherosclerosis and its risk factors, serum
      insulin was measured at fasting (n = 888) and at 2 hours after an oral glucose
      load (n = 811; known diabetic subjects were excluded). The study population
      comprised an age- and sex-stratified random sample of men and women aged 40 to 79
      years. Atherosclerosis in the common and internal carotid arteries was assessed
      twice (in 1990 and 1995) by duplex sonography. Progression during the 5-years
      follow-up was defined by an increase in the atherosclerosis score of more than
      the doubled measurement error (> 27%) or by the occurrence of new plaques.
      Subjects were stratified in quintiles according to baseline serum insulin at
      fasting or 2 hours after glucose loading. RESULTS: Logistic regression analysis
      revealed a significant association of carotid atherosclerosis with both low and
      high insulin (U-shaped relation). This finding was found before and after
      adjustment for several covariates (sex, age, body mass index, glucose tolerance,
      triglycerides, apolipoproteins Al and B, fibrinogen, blood pressure status,
      behavioral variables, and socioeconomic status). This relation applied equally to
      fasting and postglucose insulin and was more pronounced in the prospective
      analysis than in the cross-sectional analysis. CONCLUSIONS: We conclude that both
      "hypoinsulinemia" and hyperinsulinemia are independent risk indicators of carotid
      atherosclerosis.

PMID- 9183342
TI  - Stroke recurrence in diabetics. Does control of blood glucose reduce risk?
AB  - BACKGROUND AND PURPOSE: Patients with diabetes are at increased risk of stroke.
      Risk might be reduced if blood glucose level were controlled. METHODS: In a
      population-based study, we enrolled 621 patients within a month of an initial
      ischemic stroke and followed them regularly twice annually; 198 were diabetic. We
      monitored blood glucose level in 142 (72%) using glycosylated hemoglobin (HbAlc).
      Recurrent stroke frequency was determined by history, examination, and medical
      records. Cox proportional hazards models were used to examine the relationship
      between risk of recurrent stroke and HbAlc level. The models included interaction
      with time-dependent HbAlc level and history of diabetes, selected medical
      comorbidities, age, and sex. HbAlc level was analyzed as both a continuous and a
      dichotomous variable (ie, controlled versus uncontrolled); "controlled" was
      defined with different cut points. RESULTS: All but 17 patients (12%) whose blood
      glucose was monitored were well controlled (HbAlc < 8%). HbAlc level was not
      associated with increased risk of stroke recurrence (hazard ratio [HR], 0.87 per
      1% increment in HbAlc; 95% confidence interval [CI], 0.623 to 1.219), nor was
      there a trend toward increased risk of recurrent stroke as the cut point defining
      "controlled" increased: with HbAlc at < 6%, the HR for the uncontrolled group was
      0.51 (95% CI, 0.176 to 1.503); at < 7%, it was 0.43 (95% CI, 0.089 to 1.923); and
      at < 8%, it was also 0.43 (95% CI, 0.057 to 3.317). CONCLUSIONS: Among diabetic
      patients with an initial stroke, no association between HbAlc level over time and
      risk of stroke recurrence was found. However, most patients in this cohort were
      well controlled, and any adverse effect of poor control could not be adequately
      tested.

PMID- 9183343
TI  - Silent brain infarction on magnetic resonance imaging and neurological
      abnormalities in community-dwelling older adults. The Cardiovascular Health
      Study. CHS Collaborative Research Group.
AB  - BACKGROUND AND PURPOSE: Infarctlike lesions are frequently detected in
      symptomatic and asymptomatic older persons undergoing cerebral MRI, but their
      significance in older adults has not been examined. We determined the prevalence
      of MRI infarcts in a population-based sample of men and women aged > or = 65
      years and related these findings to demographic, cognitive, and neurological
      status. METHODS: MRI scanning was performed in 3660 Cardiovascular Health Study
      (CHS) participants after brief neurological examinations and tests of cognitive
      function. MRIs were read centrally for the presence of an infarct > or = 3 mm in
      diameter or smaller infarctlike lesions. RESULTS: MRI infarcts were detected in
      1131 of 3647 participants with readable infarct information (31%) and in 961 of
      the subgroup of 3397 participants (28%) without known prior stroke ("silent" MRI
      infarcts). Smaller infarctlike lesions were found in 196 of 2516 participants who
      had no MRI infarcts > or = 3 mm. MRI infarcts were more common in participants
      who were older, had prior stroke, impaired cognition, visual field deficits,
      slowed repetitive finger tapping (all P < .0001), weakness on toe and heel
      walking, and history of memory loss, coma, or migraine headaches. Multivariate
      analysis in those without prior stroke showed strong associations of silent MRI
      infarcts with older age, history of migraines, lower digit symbol scores, and
      more abnormalities on neurological examination. CONCLUSIONS: MRI evidence of
      brain infarction is common in older men and women without a clinical history of
      stroke. Their strong associations with impaired cognition and neurological
      deficits suggest that they are neither silent nor innocuous.

PMID- 9183344
TI  - Perspectives of stroke in persons living in Seoul, South Korea. A survey of 1000
      subjects.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to investigate the
      perspectives of stroke in persons who live in Seoul, South Korea, a country which
      is unique in that the social and political status of traditional (herbal)
      medicine is equal to that of western (modern) medicine. METHODS: We randomly
      selected 1000 persons living in Seoul, South Korea, and performed open-ended
      telephone interviews regarding stroke risk factors, symptoms, and the choice of
      treatment for stroke. We also asked whether the subjects would prefer to visit
      western-medicine doctors or traditional-medicine doctors if they developed
      stroke. RESULTS: Twenty-nine percent of the interviewees responded correctly that
      the most important risk factor for stroke is hypertension. However, other major
      factors, such as cigarette smoking, diabetes mellitus, and heart disease, were
      greatly underappreciated, while less important risk factors such as
      hyperlipidemia/obesity, stress, and exposure to coldness were overappreciated.
      Also, although 65% of the subjects correctly identified paresis as the most
      important symptom of stroke, tremor was indicated incorrectly as an important
      symptom of stroke. Regarding the choice of treatment, only 46% responded that
      visiting a hospital is the most important method of treatment, whereas a
      significant percentage of the subjects responded that they would prefer herbal
      medicine and other traditional methods of treatment. Generally, the older and
      less educated the subjects, the more they prefer to depend on traditional
      medicine. CONCLUSIONS: These data show that perspectives of stroke are heavily
      influenced by the presence of traditional medicine in Korea, especially in older
      and less educated persons. This perspective significantly deviates from the
      scientific concept regarding the etiology, symptoms, and treatment of stroke.
      Current science-based health education is urgently needed in this country.

PMID- 9183345
TI  - Effects of surgical revascularization on outcome of patients with pediatric
      moyamoya disease.
AB  - BACKGROUND AND PURPOSE: We reviewed surgically treated patients with pediatric
      moyamoya disease and examined whether vasoreconstructive surgeries reduced the
      risk of recurrent ischemic attacks and changed overall outcomes in terms of the
      patients' performance and intellectual status. METHODS: Sixty-four hemispheric
      sides in 34 pediatric moyamoya disease patients who received surgical treatment
      were examined. We performed superficial temporal artery to middle cerebral artery
      (STA-MCA) bypass and encephalo-duro-arterio-myo-synangiosis (EDAMS) on 48 sides
      (combined group) and indirect bypass surgery such as EDAMS on 16 sides (indirect
      group). These 34 patients were observed postoperatively from 1 to 14 years (mean
      +/- SD, 6.6 +/- 3.8 years) and were examined for the incidence of recurrent
      ischemic attack. Of the 34 patients, 23 were followed up for > 5 postoperative
      years, and their overall outcomes in terms of their performance and intellectual
      status were determined. RESULTS: Perioperative ischemic events (< or = 2 weeks
      after surgery) occurred in 5 surgeries (31%) of the indirect group and in 6 (13%)
      of the combined group (P = NS). The incidence of postoperative ischemic events (>
      2 weeks after surgery) was significantly reduced in the combined group (10%)
      compared with the indirect group (56%; P < .01). Of the 23 patients observed > 5
      years, 7 patients (30%) were mentally retarded and regarded as having a fair
      outcome. CONCLUSIONS: Combined surgery (STA-MCA bypass with EDAMS) for pediatric
      moyamoya disease was effective in reducing the risk of postoperative ischemic
      attacks compared with indirect surgery. Surgical revascularization may be
      effective in preventing intellectual deterioration and improving overall outcome.

PMID- 9183346
TI  - Measurement properties of the NIH Stroke Scale during acute rehabilitation.
AB  - BACKGROUND AND PURPOSE: The scale of stroke impairment characteristics by Brott
      and associates, the National Institutes of Health (NIH) Stroke Scale, has been
      used widely in various studies of stroke outcome; however, the measurement
      properties of the items applied to patients during medical rehabilitation have
      not been evaluated thoroughly. This study evaluated the extent to which scale
      items cohere to define a unidimensional construct and have a useful range for
      application to patients during medical rehabilitation. METHODS: Rating scale (or
      Rasch) analysis of the 15 NIH Stroke Scale items was conducted using the BIGSTEPS
      computer program to evaluate (1) the range of impairment assessed by the items,
      (2) the items' coherence with an underlying construct of impairment, and (3)
      range of impairment measured in rehabilitation patients. We sought to maximize
      the range of impairment measured by conducting analyses recursively; at each
      subsequent step, the worst fitting item was deleted or rescored. The sample
      comprised 1291 admission and discharge records from 693 rehabilitation inpatients
      with stroke. RESULTS: Thirteen items arrayed the sample across a sufficient range
      of impairment. The limb ataxia item fit poorly and was deleted; lower ratings for
      this item were associated with higher scores on the total scale. Pupillary
      response was also deleted because ratings reflected poor congruence with the
      total score. Best language was rescored because intermediate ratings were
      inconsistently related to the total score. Patients with hemorrhagic strokes had
      poorer fitting measures than did patients with ischemic strokes. CONCLUSIONS: The
      items in a revised NIH Stroke Scale worked well together to define the severity
      of impairment resulting from stroke that is observed during medical
      rehabilitation. Directions regarding limb ataxia should be modified to indicate
      untestability due to hemiplegia.

PMID- 9183347
TI  - Retrospective assessment of initial stroke severity with the Canadian
      Neurological Scale.
AB  - BACKGROUND AND PURPOSE: The severity of the initial neurological deficit is a
      critical determinant of outcome after acute stroke. Retrospective outcome studies
      are generally limited by a lack of quantitative data relating to this initial
      stroke severity. We evaluated the validity and reliability of measuring initial
      stroke severity retrospectively with the Canadian Neurological Scale (CNS).
      METHODS: The CNS was used to prospectively score the initial neurological deficit
      in a series of patients with acute ischemic stroke (n = 24). An algorithm was
      devised for applying the CNS retrospectively on the basis of information in the
      patient's hospital discharge summary. Those dictating the discharge summaries
      were not aware of the study, and the retrospective scoring was performed without
      reference to other scores. The level of agreement between the prospective and
      retrospective scores (validity) and both intraobserver and interobserver
      reliability for the retrospective scores were determined. RESULTS: Agreement was
      high between retrospective and prospective scores (r = .84, R2 = .71, P < .0001),
      between two sets of retrospective scores obtained by one rater (r = .95, R2 =
      .91, P < .0001), and between retrospective scores obtained by different raters (r
      = .91, R2 = .82, P < .0001). Weighted kappa statistics (kappa w) for
      prospectively versus retrospectively scored items varied from almost perfect
      (kappa w > 0.81 for level of consciousness and orientation) to substantial (kappa
      w = 0.68 for speech) and moderate (kappa w = 0.41 to 0.60 for facial weakness,
      proximal arm, distal arm, proximal leg, and distal leg strength). Using the
      retrospective algorithm, there was almost perfect intraobserver and interobserver
      reliability for each of the individual CNS items (kappa w = 0.81 to 1.00).
      CONCLUSIONS: These data show that retrospective scoring of initial stroke
      severity using an algorithm based on the CNS is valid and can be reliably
      performed using information available in hospital discharge summaries.

PMID- 9183348
TI  - Prognostic value of admission blood pressure in patients with intracerebral
      hemorrhage. Keio Cooperative Stroke Study.
AB  - BACKGROUND AND PURPOSE: Patients with acute stroke on admission to the hospital
      are often found to have high blood pressure. The purpose of the present study was
      to investigate the prognostic value of admission blood pressure in patients with
      acute intracerebral hemorrhage, including putaminal, thalamic, subcortical,
      cerebellar, and pontine hemorrhage. METHODS: A total of 1701 patients with
      intracerebral hemorrhage of the putamen (n = 776; mean +/- SD age, 58 +/- 14
      years) thalamus (n = 538; 63 +/- 12 years), subcortex (n = 153; 61 +/- 16 years),
      cerebellum (n = 110; 64 +/- 11 years), and pons (n = 124; 59 +/- 13 years) were
      examined. The mean blood pressure on admission in patients with a fatal outcome
      was compared with that in patients who survived. RESULTS: The mean age in each
      patient group (putaminal, thalamic, subcortical, cerebellar, and pontine
      hemorrhage) with fatal outcome was older than that with nonfatal outcome, while
      ANCOVA indicated no correlation between age and blood pressure on admission or
      age and volume of hematoma. The mean arterial blood pressure on hospital
      admission was 126.9 +/- 25.8 mm Hg (+/-SD) in cases of putaminal. 127.4 +/- 22.6
      mm Hg in thalamic, 116.4 +/- 20.6 mm Hg in subcortical, 123.5 +/- 23.9 mm Hg in
      cerebellar, and 133.0 +/- 26.0 mm Hg in pontine hemorrhage. The mean blood
      pressure on admission in patients with a fatal outcome among those with putaminal
      (136.0 +/- 36.3 mm Hg) and thalamic (133.2 +/- 22.1 mm Hg) hemorrhage was
      significantly higher than that in those with a nonfatal outcome (123.8 +/- 20.6
      mm Hg for putaminal, 101.6 +/- 22.5 mm Hg for thalamic) (P < .01). No correlation
      between mean blood pressure and outcome was observed in the patients with
      subcortical (116.5 +/- 22.2 mm Hg for nonfatal, 114.9 +/- 22.0 mm Hg for fatal
      outcome), cerebellar (125.2 +/- 22.2 mm Hg, 116.9 +/- 28.8 mm Hg), and pontine
      (129.9 +/- 23.8 mm Hg, 136.0 +/- 27.7 mm Hg) hemorrhage. The volume of hematoma
      on admission in patients with fatal outcome with putaminal (58.2 +/- 24.4 mL),
      thalamic (27.0 +/- 13.1 mL), subcortical (32.9 +/- 14.4 mL), and cerebellar (31.4
      +/- 28.6 mL) hemorrhage was greater than that in those with nonfatal outcome
      (20.8 +/- 11.4 mL, 7.1 +/- 4.8 mL, 18.3 +/- 10.6 mL, and 8.1 +/- 4.2 mL,
      respectively; P < .01), while no correlation between volume of hematoma and
      outcome was observed in patients with pontine hemorrhage. CONCLUSIONS: The above
      data suggest that an increased mean blood pressure and volume of hematoma on
      admission in putaminal and thalamic hemorrhage were related to increased
      mortality, while in patients with subcortical, cerebellar, and pontine
      hemorrhage, the mean blood pressure was not related to the clinical outcome.

PMID- 9183349
TI  - Atherosclerotic changes in the carotid artery bulb as measured by B-mode
      ultrasound are associated with the extent of coronary atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Ultrasound is increasingly used to measure
      atherosclerotic development in carotid and femoral arteries. The aim of this
      study was to investigate the relationship between coronary atherosclerosis as
      measured by quantitative angiography and peripheral atherosclerosis as measured
      by ultrasound in three different arterial regions. METHODS: Patients (n = 32)
      with at least two coronary segments with visible signs of atherosclerosis as
      defined in a computer-assisted analysis of coronary angiograms were also examined
      with B-mode ultrasound. The extent of coronary atherosclerosis was expressed as
      the average diameter stenosis of coronary segments, and peripheral
      atherosclerosis was defined as intima-media thickness (IMT) and plaque occurrence
      in the common carotid artery, the carotid bulb, and the common femoral artery.
      RESULTS: The results showed a significant correlation between the ultrasound
      measurement of IMT of the carotid bulb and diameter stenosis of the included
      coronary segments (r = .68, P = .01) and of carotid plaques and diameter stenosis
      (P < .001). The correlation between common carotid IMT and diameter stenosis of
      included coronary segments was not statistically significant (r = .31, NS). There
      were no significant relationships between common femoral IMT or femoral plaques
      and diameter stenosis of included coronary segments. CONCLUSIONS: Although this
      study is small, it points to a very important aspect of ultrasound measurements
      of atherosclerosis: measurements performed in the common carotid artery or the
      femoral artery may not relate to coronary atherosclerosis in the same way as
      measurements performed in the carotid bulb. The findings underline the importance
      of measuring IMT not only in the common carotid artery but also in the carotid
      bulb and present data separately. These results have to be confirmed in a larger
      scale study.

PMID- 9183350
TI  - Effect of PCO2 changes induced by head-upright tilt on transcranial Doppler
      recordings.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) monitoring of mean blood flow
      velocity (mV) during head-upright tilt can allow testing of cerebral
      autoregulation. Nonetheless, head-upright tilt can induce changes in the
      ventilation-perfusion relationship and/or respiratory activity that might
      influence TCD data. METHODS: Forty-eight healthy volunteers underwent monitoring
      of mV and end-tidal CO2 in the horizontal position and during head-upright tilt.
      RESULTS: Both mV and end-tidal CO2 significantly decreased in orthostasis (P <
      .01). Linear regression analysis showed a significant linkage between end-tidal
      CO2 and mV changes (r = .83, P < .01). CONCLUSIONS: Changes in ventilation
      perfusion ratio and in the respiratory pattern induced by head-upright tilt can
      significantly influence TCD data by determining a PCO2 decrease.

PMID- 9183351
TI  - Predictors of hemorrhagic transformation occurring spontaneously and on
      anticoagulants in patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a common evolution of
      large-volume ischemic lesions, particularly of cardioembolic origin. We used
      transcranial Doppler ultrasound (TCD), single-photon emission computed tomography
      (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO), and the Toronto
      Embolic Scale (TES) to decide (1) whether TCD, HMPAO-SPECT, and TES can improve
      on clinical and CT tests to predict spontaneous HT and (2) whether SPECT can help
      to predict the outcome of symptomatic HT. METHODS: Prognostic criteria included
      Canadian Neurological Scale (CNS) scores < or = 50 on admission, early ischemic
      changes on CT, M1 middle cerebral artery occlusion on TCD, the focal absence of
      brain perfusion on SPECT, and a high risk of cardiogenic embolism on TES.
      RESULTS: In part 1, 85 consecutive patients admitted within the first 6 hours
      were studied. No patient received thrombolysis. HT was found in 11 patients (13%)
      at 3 to 5 days. Admission CNS and CT were not predictive of HT: odds ratios (95%
      confidence intervals) were 0.49 (0.18 to 1.23) (P = .1) and 0.88 (0.23 to 3.45)
      (P = .8), respectively, TCD, SPECT, and TES were significant predictors of HT (P
      < .05), as follows: TCD, 8.67 (1.42 to 70.59); SPECT, 17.40 (2.69 to 170.89); and
      TES, 18.13 (2.6 to 406.86). In part 2, 490 consecutive patients were studied and
      21 (4%) had symptomatic HT, of which 12 had focal hypoperfusion on SPECT at 4
      days after stroke onset and 9 had focal hyperperfusion. Patients with
      hypoperfusion had larger CT lesions (115 +/- 97 versus 42 +/- 29 cm3; P = .04)
      and poorer outcome at 2 weeks (CNS, 38 +/- 45 versus 96 +/- 10; P = .001),
      including death (6/12 versus 0/9; P = .04); compared with those with
      hyperperfusion on SPECT. CONCLUSIONS: High risk of cardioembolism, M1 middle
      cerebral artery occlusion, and absence of collateral flow evaluated by TES, TCD,
      and SPECT help to identify patients at risk for spontaneous HT. Although TES was
      the most powerful predictor of HT, SPECT is the best single adjunct to the triage
      of clinical and CT tests. Patients with brain hyperperfusion on HMPAO-SPECT after
      symptomatic HT have better chances for recovery.

PMID- 9183352
TI  - Intracranial microembolic signals in 500 patients with potential cardiac or
      carotid embolic source and in normal controls.
AB  - BACKGROUND AND PURPOSE: We undertook this study to evaluate the prevalence and
      clinical correlations of Doppler microembolic signals (MES) in stroke-prone
      patients. METHODS: Patients with potential cardiac (n = 300) or carotid (n = 100)
      embolic source and control subjects (n = 100) were monitored with transcranial
      Doppler sonography for MES. Transthoracic (n = 192) and/or transesophageal (n =
      134) echocardiography and carotid studies (continuous-wave Doppler, n = 181;
      color-coded duplex, n = 47) were performed in all patients with potential native
      cardioembolic source. Carotid disease was evaluated by means of continuous-wave
      Doppler (n = 87), color-coded duplex (n = 70), or intra-arterial angiography (n =
      24) in patients with potential carotid embolic source. RESULTS: Overall MES
      prevalence was 23% in patients with potential native cardioembolic source
      (infective endocarditis [n = 7] 43%, left ventricular aneurysm [n = 38] 34%,
      intracardiac thrombus [n = 23] 26%, dilative cardiomyopathy [n = 39] 26%,
      nonvalvular atrial fibrillation [n = 24] 21%, valvular disease [n = 80] 15%), 55%
      in patients with prosthetic cardiac valves (mechanical [n = 77] 58%, porcine [n =
      7] 43%, homografts [n = 5] 20%), 28% in patients with carotid disease
      (symptomatic [n = 46] 52%, asymptomatic [n = 54] 7%; P < .01), and 5% in control
      subjects. No relationship between MES counts and patients' age, sex, or actual
      medication was noted. The sensitivity and specificity of MES detection in
      identifying patients with potential embolic sources were 31% and 95%,
      respectively. CONCLUSIONS: Our study confirmed the reported clinical significance
      of MES in patients with carotid disease and the high specificity of this
      technique. The demonstrated low sensitivity of MES detection could be due to
      short monitoring duration or application of antihemostatic treatment. Prospective
      large-scale studies are needed to determine the definitive value of MES detection
      as a diagnostic method in patients with potential cardioembolic source.

PMID- 9183353
TI  - Grading carotid stenosis with ultrasound. An interlaboratory comparison.
AB  - BACKGROUND AND PURPOSE: Carotid ultrasound had modest accuracy in the North
      American Symptomatic Carotid Endarterectomy Trial (NASCET) of carotid
      endarterectomy in predicting severe carotid stenosis when a 250-cm/s peak
      systolic velocity (PSV) criterion was applied to different laboratories. We
      compared the performance of two independent laboratories using similar equipment
      (ATL-HDI Ultramark 9) but different interpretation criteria. METHODS: Consecutive
      patients who underwent both color-coded duplex ultrasound and intra-arterial
      digital subtraction angiography were studied. PSV was determined with angle
      correction at the site of the tightest arterial narrowing. Carotid stenosis was
      measured on angiograms using the North American (N) method. Sensitivity,
      specificity, and positive (PPV) and negative (NPV) predictive values with 95%
      confidence intervals were calculated for each laboratory. RESULTS: In 87
      patients, 174 bifurcations were imaged. A 250-cm/s criterion was the best single
      predictor of a > 70% N stenosis at one laboratory (sensitivity 93% [95%
      confidence interval, 85 to 101], specificity 86% [76 to 96], PPV 75% [62 to 87],
      and NPV 96% [90 to 102]) but had modest parameters at the other laboratory (50%
      [34 to 64], 87%, [77 to 97], 60 [44 to 76], and 91 [82 to 100], respectively).
      However, the diagnostic criteria routinely used in the second laboratory included
      different velocity values, which when applied decreased specificity by 17% but
      increased sensitivity by 35% (85% [74 to 96], 70% [56 to 84], 90% [81 to 99], and
      77% [64 to 90], respectively). CONCLUSIONS: Despite the use of similar equipment,
      ultrasound grading of carotid stenosis is operator dependent and relies on
      different and individually validated criteria. Greater sensitivity of ultrasound
      screening is achieved by applying diagnostic criteria specific to each
      laboratory. Multicenter studies should use laboratory-specific criteria and a
      local validation process.

PMID- 9183354
TI  - STAR MR angiography for rapid detection of vascular abnormalities in patients
      with acute cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: We undertook to investigate the usefulness of signal
      targeting with alternating radiofrequency magnetic resonance angiography (STAR
      MRA) in the diagnosis of acute cerebrovascular disease. The potential advantage
      of the technique is that angiographic images can be acquired in less than 1
      minute. METHODS: We studied 19 patients (11 men and 8 women, ranging in age from
      36 to 84 years [mean age, 66 years]) presenting with signs and symptoms of acute
      stroke. Patients underwent STAR MRA and three-dimensional fast imaging with
      steady-state precession (3D FISP) MRA. The MRAs were analyzed as to image quality
      and vascular abnormalities in the vascular territory of stroke as defined by
      diffusion-weighted imaging abnormalities and compared using a Wilcoxon signed
      rank test. RESULTS: STAR MRAs had slightly inferior image quality compared with
      3D FISP MRA (P < .05). STAR MRA and 3D FISP MRA agreed in 18 of 19 cases
      regarding vascular abnormalities in the territory of the infarct (occlusion, n =
      8; stenosis, n = 4; no abnormality, n = 6). In one patient, the techniques
      disagreed, when 3D FISP MRA was normal and STAR MRA demonstrated a vessel
      occlusion in the vascular territory of a stroke as defined by diffusion-weighted
      imaging abnormalities (P > .05). CONCLUSIONS: Despite slightly inferior image
      quality compared with 3D FISP MRA, STAR MRA is comparable with 3D FISP MRA in
      depicting abnormalities in the proximal parts of the cerebral arteries
      corresponding to ischemic regions on diffusion-weighted imaging, in a strikingly
      shorter acquisition time. Further studies are necessary to confirm that the
      smaller branches are better shown by using longer inversion times.

PMID- 9183355
TI  - In vivo angioplasty prevents the development of vasospasm in canine carotid
      arteries. Pharmacological and morphological analyses.
AB  - BACKGROUND AND PURPOSE: To study the effects of in vivo transluminal balloon
      angioplasty (TBA) on the structure and function of the arterial wall, a canine
      model of hemorrhagic cerebral vasospasm of the high cervical internal carotid
      artery (ICA) was used. This model was also used to determine whether TBA
      performed before clot placement could prevent the development of vasospasm.
      METHODS: Twelve dogs underwent surgical exposure of both distal-cervical ICAs,
      followed by baseline angiography. One randomly selected ICA in each dog was then
      subjected to in vivo TBA and repeated angiography. Both distal ICAs were then
      surrounded with blood clots held by silicone elastomer sheaths. Seven days later
      angiography was repeated, and all animals were killed. The ICAs in four animals
      were perfusion-fixed in situ for morphological analysis by electron microscopy,
      and the arteries in the remaining eight animals were removed and immediately
      immersed in oxygenated Krebs' solution. Contractile responses of isolated
      arterial rings from each ICA were recorded after treatment with KCl,
      noradrenaline, serotonin, and prostaglandin F2 alpha, while relaxations in
      response to the calcium ionophore A23187 and papaverine were recorded after tonic
      contraction to noradrenaline had been established. The morphology and
      pharmacological responses of ICAs that had been exposed to blood with or without
      prior TBA were compared with data obtained from control arterial segments of
      intact, more proximal regions of the ICAs from each animal. RESULTS: TBA resulted
      in immediate angiographic enlargement of the ICA lumen that was still evident 7
      days later despite the placement of clotted blood around the artery. Scanning and
      transmission electron microscopy demonstrated flattening of the intima and
      internal elastic lamina in these dilated arteries, associated with patchy losses
      of endothelial cells. In contrast, ICAs that had been exposed to clotted blood
      but had not undergone prior TBA developed consistent angiographic and
      morphological vasospasm. In comparison with control vessels and nondilated
      vasospastic vessels, vessels dilated with TBA and then exposed to clotted blood
      showed significantly diminished responses to all compounds tested, with the
      exception of prostaglandin F2 alpha. CONCLUSIONS: These results indicate that in
      vivo TBA results in a degree of functional impairment of vascular smooth muscle
      that persists for at least 7 days. This result is consistent with previous
      observations of the acute effects of TBA in isolated arteries. Furthermore, these
      results support the hypothesis that normal smooth muscle function is required for
      the development of vasospasm. Finally, these results indicate that TBA performed
      before the onset of vasospasm prevents its development.

PMID- 9183356
TI  - Neural grafting to experimental neocortical infarcts improves behavioral outcome
      and reduces thalamic atrophy in rats housed in enriched but not in standard
      environments.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate whether
      grafting of fetal neocortical tissue 1 week after focal brain ischemia improved
      behavioral outcome and reduced secondary thalamic atrophy. METHODS: One week
      after distal ligation of the right middle cerebral artery in spontaneously
      hypertensive male rats, blocks of fetal neocortex (embryonic day 17) were
      homografted to rats housed in standard or enriched environments. Control
      infarcted nongrafted rats were housed in the enriched environment. Behavioral
      outcome was repeatedly tested until the rats were killed 20 weeks after the
      ligation. Ten days earlier, a mixture of 2% Fluoro-Gold and 10% biotinylated
      dextran amine was injected into the transplants for retrograde and anterograde
      tracing of graft-host connections. RESULTS: Grafted and nongrafted rats with
      enriched housing performed significantly better than grafted rats with standard
      housing on a rotating pole and a prehensile traction test. Grafted "enriched"
      rats were moreover significantly better than grafted "standard" rats and
      nongrafted enriched rats in a rotation test and a postural and locomotor tail
      position test. In the latter test, nongrafted enriched rats performed
      significantly better than grafted standard rats. The lesion-induced atrophy in
      posterior thalamus with its major sensorimotor cortex relay nuclei was
      significantly reduced in grafted enriched rats compared with nongrafted enriched
      rats. Afferent and efferent graft-host connections were identified in both
      grafted groups. Graft volumes did not differ. CONCLUSIONS: Neural grafting
      enhanced functional outcome and reduced thalamic atrophy only when combined with
      housing in enriched environments.

PMID- 9183357
TI  - Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury.
AB  - BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic
      cytokine that rapidly upregulates in the brain after injury. The present study
      was designed to explore the pathophysiological significance of brain TNF-alpha in
      the ischemic brain by systematically evaluating the effects of lateral
      cerebroventricular administration of exogenous TNF-alpha and agents that block
      the effects of TNF-alpha on focal stroke and by examining the potential direct
      toxic effects of TNF-alpha on cultured neurons to better understand how TNF-alpha
      might mediate stroke injury. METHODS: TNF-alpha (2.5 or 25 pmol) was administered
      intracerebroventricularly to spontaneously hypertensive rats 24 hours before
      permanent or transient (80 minutes and 160 minutes) middle cerebral artery
      occlusion (MCAO). Animals were examined 24 hours later for neurological deficits
      and ischemic hemisphere necrosis and swelling. In some of these studies,
      neutralizing anti-TNF-alpha monoclonal antibody (mAb) (60 pmol) was injected
      intracerebroventricularly 30 minutes before exogenous TNF-alpha (25 pmol). In
      addition, the effects of blocking endogenous TNF-alpha on permanent focal
      ischemic injury were determined with the use of either mAb (60 pmol) or soluble
      TNF receptor I (sTNF-RI) (0.3 or 0.7 nmol) administered intracerebroventricularly
      30 minutes before and 3 and 6 hours after MCAO. Finally, the direct neurotoxic
      effects of TNF-alpha were studied in cultured rat cerebellar granule cells
      exposed to TNF-alpha (10 to 2000 U/mL for 6 to 24 hours), and neurotransmitter
      release, glutamate toxicity, and oxygen radical toxicity were studied. RESULTS:
      TNF-alpha increased the percent hemispheric infarct induced by permanent MCAO in
      a dose-related manner from 13.1 +/- 1.3% (vehicle) to 18.9 +/- 1.7% at 2.5 pmol
      (P < .05) and 27.1 +/- 1.3% at 25 pmol (P < .0001). The high dose of TNF-alpha
      increased ischemia-induced forelimb deficits from 1.6 +/- 0.2 to 2.3 +/- 0.2 (P <
      0.1). TNF-alpha (2.5 pmol) also increased the infarction induced by 80 or 160
      minutes of transient MCAO from 1.9 +/- 0.9% to 4.3 +/- 0.4% (P < .01) and from
      14.2 +/- 1.3% to 21.6 +/- 2.2% (P < .05), respectively. The exacerbation of
      infarct size, swelling, and neurological deficit after exogenous TNF-alpha was
      reversed by preinjection of 60 pmol mAb. Blocking endogenous TNF-alpha also
      significantly reduced focal ischemic brain injury. Treatment with 60 pmol mAb
      before and after permanent MCAO significantly reduced infarct size compared with
      control (nonimmune) antibody treatment by 20.2% (P < .05). Reduced brain
      infarction also was produced by brain administration of 0.3 nmol (decreased
      18.2%) or 0.7 nmol (decreased 26.1%, P < .05) sTNF-RI before and after focal
      stroke. The intracerebroventricular administration of TNF-alpha or sTNF-RI did
      not alter brain or body temperature, blood gases or pH, blood pressure, blood
      glucose, or general blood chemistry. In cultured cerebellar granule cells, the
      application of TNF-alpha did not directly affect neurotransmitter release or
      glutamate or oxygen free radical toxicity. CONCLUSIONS: These studies demonstrate
      that exogenous TNF-alpha exacerbates focal ischemic injury and that blocking
      endogenous TNF-alpha is neuroprotective. The specificity of the action(s) of TNF
      alpha was demonstrated by antagonism of its effects with specific anti-TNF-alpha
      tools (ie, mAb and sTNF-RI). TNF-alpha toxicity does not appear to be due to a
      direct effect on neurons or modulation of neuronal sensitivity to glutamate or
      oxygen radicals and apparently is mediated through nonneuronal cells. These data
      suggest that inhibiting TNF-alpha may represent a novel pharmacological strategy
      to treat ischemic stroke.

PMID- 9183358
TI  - DNA scission after focal brain ischemia. Temporal differences in two species.
AB  - BACKGROUND AND PURPOSE: Species- and model-dependent differences in cell response
      to focal brain ischemia may underlie differences in adhesion receptor expression.
      The aim of this study was to quantitatively evaluate the spatial and temporal
      distribution of dUTP incorporation into damaged DNA, as an indicator of ischemic
      injury, in the corpus striatum. METHODS: Cerebral ischemia was produced in 16
      nonhuman primates and 19 rats by occluding the middle cerebral artery (MCA:O)
      with reperfusion for various periods. In situ dUTP was incorporated into cells
      with DNA damage by terminal deoxynucleotidyl transferase (TdT), DNA polymerase I,
      or the Klenow fragment of DNA polymerase. Dual immunolabeling experiments with
      immunoprobes against neuronal, vascular, or glial marker proteins were performed.
      RESULTS: Significant topographical differences in dUTP between the two species
      were seen. In both models the TdT and polymerase I regions changed
      characteristically during focal ischemia. The number and density of dUTP-labeled
      cells increased with time from MCA:O and were dramatically different between the
      species (2P < .001). By 2 hours of ischemia, the density of dUTP label was 48.8
      +/- 10.3 cells/mm2 in the primate and 2.4 +/- 0.8 cells/mm2 in the rat (2P <
      .05), but these values became nearly identical by 24 hours of reperfusion. In the
      primate, 80.0 +/- 6.6% of labeled cells displayed microtubule-associated protein
      2 antigen (at 2-hour MCA:O), while 1.8 +/- 0.5% were associated with microvessels
      at 24 hours of reperfusion. CONCLUSIONS: In situ detection of DNA damage,
      accomplished by three methods, reveals distinct temporal, topographical, and
      density differences in ischemic injury to cells in the primate and the rat corpus
      striatum as a result of MCA:O.

PMID- 9183359
TI  - Glycine site antagonist attenuates infarct size in experimental focal ischemia.
      Postmortem and diffusion mapping studies.
AB  - BACKGROUND AND PURPOSE: The glycine site on the N-methyl-D-aspartate (NMDA)
      receptor complex offers a therapeutic target for acute focal ischemia,
      potentially devoid of most side effects associated with competitive and
      noncompetitive NMDA antagonists. METHODS: A novel glycine receptor antagonist,
      ZD9379, was studied in 70 Sprague-Dawley rats using the suture occlusion model of
      permanent middle cerebral artery occlusion (MCAO). In the first experiment, 20
      rats received an initial bolus of vehicle or 10 mg/kg ZD9379 (n = 10 in each
      group) 30 minutes after MCAO, followed by a continuous infusion of the same dose
      per hour for 4 hours. Diffusion-weighted MRI with echo-planar acquisition was
      used to generate maps of the apparent diffusion coefficient (ADC) of water. In a
      second experiment, 50 rats were assigned to five groups: vehicle and 10, 5, 2.5,
      and 1 mg/kg ZD9379 (n = 10 in each group) with the same dosing protocol but no
      imaging. In both experiments, infarct volume was determined by 2,3,5
      triphenyltetrazolium chloride staining. RESULTS: In the first experiment, before
      therapy was begun, there was no significant difference in ADC-derived ischemic
      lesion volume between the two groups. Over time, the 10-mg/kg ZD9379-treated rats
      had a significant delayed regional recovery of reduced ADC values in the
      peripheral parietal cortex (P = .0156). Postmortem corrected infarct volume at 24
      hours after MCAO was significantly smaller in the group treated with 10 mg/kg
      ZD9379 than in the vehicle group (119.2 +/- 52.2 versus 211.2 +/- 50.0 mm3 [mean
      +/- SD]; P = .0008; a reduction of 43.6%). In the second experiment, postmortem
      corrected infarct volumes in rats receiving 10, 5, and 2.5 mg/kg ZD9379 were
      significantly smaller than in those receiving vehicle, a reduction of 42.6%,
      51.4%, and 42.9%, respectively (P = .0001). CONCLUSIONS: This study demonstrates
      that 2.5- to 10-mg/kg doses of ZD9379 initiated 30 minutes after MCAO
      significantly reduced infarct size. Diffusion mapping disclosed a delayed
      treatment effect of this glycine antagonist in focal ischemia, confirmed by the
      postmortem study.

PMID- 9183360
TI  - Role of potassium channels in relaxations of canine middle cerebral arteries
      induced by nitric oxide donors.
AB  - BACKGROUND AND PURPOSE: The mechanisms underlying smooth muscle relaxations of
      cerebral arteries in response to nitric oxide (NO) and cyclic GMP (cGMP) are
      still not completely understood. The present study was designed to determine the
      role of potassium channels in the relaxations to NO donors 3
      morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), as well as 8-bromo
      3',5' -cGMP (a synthetic analogue of cGMP) and zaprinast (a selective cGMP
      phosphodiesterase inhibitor). METHODS: Rings of canine middle cerebral asteries
      without endothelium were suspended in Krebs-Ringer bicarbonate solution for
      isometric tension recording. The levels of cGMP were measured by
      radioimmunoassay. Relaxations to NO donors 8-bromo-cGMP and zaprinast were
      studied in the presence and in the absence of K+ channel blockers charybdotoxin
      (large-conductance Ca(2+)-activated K+ channels), glyburide (ATP-sensitive K+
      channels), 4-aminopyridine (delayed rectifier K+ channels), and BaCl2 (multiple
      types of K+ channels). RESULTS: Concentration-dependent relaxations caused by NO
      donors (SIN-1 and SNP) were significantly reduced in arteries treated with BaCl2
      (3 x 10(-4) mol/L) or charybdotoxin (3 x 10(-8) mol/L). Relaxations to 8-bromo
      cGMP were not affected by the same concentrations of BaCl2 and charybdotoxin;
      however, they were reduced by higher concentrations of BaCl2 (3 x 10(-3) mol/L)
      or charybdotoxin (10(-7) mol/L). Zaprinast-induced relaxations were significantly
      reduced by BaCl2 (3 x 10(-4) mol/L) or charybdotoxin (3 x 10(-8) mol/L).
      Glyburide (10(-5) mol/L) and 4-aminopyridine (10(-3) mol/L) did not alter the
      relaxations to SIN-1 or SNP. The production of cGMP stimulated by SIN-1 in the
      vascular smooth muscle was not affected by BaCl2 (3 x 10(-3) mol/L) or
      charybdotoxin (10(-7) mol/L). CONCLUSIONS: These results indicate that in canine
      middle cerebral arteries, a significant portion of relaxations to NO liberated
      from nitrovasodilators is mediated by large-conductance Ca(2+)-activated K+
      channels. Other K+ channels, sensitive to BaCl2, may also be involved in the
      mechanism of relaxations induced by NO.

PMID- 9183362
TI  - Ruptured dissecting aneurysm as a cause of subarachnoid hemorrhage of unverified
      etiology.
AB  - BACKGROUND AND PURPOSE: The clinical features of "aneurysmal" subarachnoid
      hemorrhage (SAH) of angiographically unverified etiology were reviewed to clarify
      the incidence and natural history of dissecting aneurysms as the hemorrhagic
      source of SAH. METHODS: We reviewed 30 patients with SAH of unverified etiology
      in whom initial CT scan showed a diffuse or anteriorly distributed subarachnoid
      blood clot. Ten of the patients had stenotic or occlusive lesions (SOCL) on
      initial angiography, and these were the main focus of this study. RESULTS: Among
      the 10 patients with SOCL on initial angiography, the lesions were located on the
      anterior circulation in 6 and on the posterior circulation in 4. Ruptured
      dissecting aneurysms were confirmed by exploratory surgery or autopsy in 6
      patients. Subsequent rupture occurred in 6 of the 10 patients (60%), and all 6 of
      these patients died as a result. CONCLUSIONS: The incidence (6/30) of dissecting
      aneurysms as the cause of SAH of unverified etiology was unexpectedly high,
      especially when initial angiography disclosed SOCL (6/10). The moribund patients
      with SOCL showed a high rate of rebleeding, and the untreated recurrent
      hemorrhages were fatal. Further MRI study is indicated for these patients to
      demonstrate the intramural hematoma. Compared with the devastating mortality
      caused by the subsequent ruptures, the extent of surgical morbidity was minor.
      Surgical intervention could therefore be justified when the following
      neuroradiological findings are present: (1) SOCL evident on angiography, (2)
      distribution of SAH on CT compatible with the location of the SOCL, and (3)
      intramural hematoma on MRI in the same region as the SOCL.

PMID- 9183361
TI  - Kainate-induced cerebrovascular dilation is resistant to ischemia in piglets.
AB  - BACKGROUND AND PURPOSE: Cerebral arteriolar dilation to N-methyl-D-aspartate
      (NMDA) is drastically reduced by anoxic stress. The effects of anoxic stress on
      cerebrovascular dilation to activation of other types of glutamate receptors are
      unknown. The purpose of this study was to examine the effects of ischemia on
      cerebral arteriolar responses to kainate in anesthetized piglets. METHODS:
      Arteriolar responses to 5 x 10(-5) mol/L and 10(-4) mol/L kainate were evaluated
      before and 10 minutes after total, global ischemia. Ischemia was induced by
      increasing intracranial pressure. We measured pial arteriolar diameters
      (approximately 100 microns) using a cranial window and intravital microscopy.
      RESULTS: Before ischemia, kainate dilated arterioles by 16 +/- 2% at 5 x 10%
      mol/L and 30 +/- 2% at 10(-4) mol/L (mean +/- SEM; n = 6). After ischemia, the
      diameter of arterioles increased by 17 +/- 3% and 26 +/- 3% to 5 x 10% and 10(-4)
      mol/L kainate, respectively (P > .05). We also investigated the mechanisms
      involved in mediating arteriolar dilation to kainate. Intravenous administration
      of N omega-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg) (n = 7) or
      indomethacin (10 mg/kg) (n = 6) individually reduced arteriolar dilation to
      kainate by approximately one half. Coadministration of L-NAME and indomethacin
      almost completely eliminated arteriolar dilation to kainate (n = 10).
      Administration of theophylline (20 mg/kg IV) did not affect dilator responses to
      kainate (n = 7). Blockade of NMDA receptors by MK801 had minimal effects on
      arteriolar dilation to kainate (n = 6). CONCLUSIONS: There are three main
      findings from this study: (1) kainate is a potent dilator agent in the neonatal
      cerebral circulation; (2) nitric oxide and prostaglandins both participate in the
      vasodilator response to kainate; and (3) in contrast to NMDA, cerebral arteriolar
      dilator responses to kainate are resistant to ischemic stress.

PMID- 9183363
TI  - Nitric oxide synthase in models of focal ischemia.
AB  - BACKGROUND AND PURPOSE: Cessation of blood flow to the brain, for even a few
      minutes, sets in motion a potential reversible cascade of events resulting in
      neuronal cell death. Oxygen free radicals and oxidants appear to play an
      important role in central nervous system injury after cerebral ischemia and
      reperfusion. Recently, divergent roles for the newly identified neuronal
      messenger molecule and oxygen radical, nitric oxide (NO), have been identified in
      various models of cerebral ischemia. Because of the chemical and physical
      properties of NO, the numerous physiological activities it mediates, and the lack
      of specific agents to modulate the activity of the different isoforms of NO
      synthase (NOS), reports regarding the role of NO in focal cerebral ischemia have
      been confounding and often conflicting. Recent advances in pharmacology and the
      development of transgenic knockout mice specific for the different isoforms of
      NOS have advanced our knowledge and clarified the role of NO in cerebral
      ischemia. METHODS: Animal models of focal ischemia employ occlusion of nutrient
      cerebral vessels, most commonly the middle cerebral artery. Primary cortical
      cultures are exposed to excitotoxic or ischemic conditions, and the activities of
      NOS isoforms or NO production are evaluated. Transgenic mice lacking expression
      of either the neuronal isoform of NOS (nNOS), the endothelial isoform of NOS
      (eNOS), or the immunologic isoform of NOS (iNOS) have been examined in models of
      excitotoxic injury and ischemia. RESULTS: Excitotoxic or ischemic conditions
      excessively activate nNOS, resulting in concentrations of NO that are toxic to
      surrounding neurons. Conversely, NO generated from eNOS is critical in
      maintaining cerebral blood flow and reducing infarct volume. iNOS, which is not
      normally present in healthy tissue, is induced shortly after ischemia and
      contributes to secondary late-phase damage. CONCLUSIONS: Pharmacological and
      genetic approaches have significantly advanced our knowledge regarding the role
      of NO and the different NOS isoforms in focal cerebral ischemia. nNOS and iNOS
      play key roles in neurodegeneration, while eNOS plays a prominent role in
      maintaining cerebral blood flow and preventing neuronal injury.

PMID- 9183364
TI  - B-waves and cerebral autoregulation.

PMID- 9183365
TI  - Is nimodipine in cardiac surgery really so bad?

PMID- 9183366
TI  - Activated protein C resistance and factor V Leiden mutation are risk factors for
      cerebral sinus thrombosis.

PMID- 9183367
TI  - [Role of endothelin in arterial hypertension. From agonists to antagonists].
AB  - Mediators synthesized or transformed in the vascular endothelium play an
      important role in modulating vessel tone and structure. The subsequent increase
      in peripheral resistance focuses attention on the hypothesis that endothelin, due
      to its vasoconstrictive effect and proliferative action, plays a role in
      hypertension. Use of converting enzyme inhibitors and endothelin receptor
      antagonists in normotensive subjects has confirmed the modulating effect of
      endothelin on vascular tone. However, these antagonists have not been found to
      have a major anti-hypertensive effect in hypertension. In animal models these
      antagonists reduce blood pressure only in case of vascular hypertrophy associated
      with over-production of endogenous endothelin. Current research suggests that
      endothelin antagonists could have a beneficial effect in certain forms of
      hypertension involving mineralocorticoids, angiotensin II or renal failure. Use
      of endothelin antagonists for hypertension will thus remain empirical until the
      stimulus for endogenous overexpression of vascular endothelin (angiotensin II
      would be a good candidate) has been identified.

PMID- 9183368
TI  - [Human immunodeficiency virus infection and AIDS in Aquitaine. 10 years'
      experience of a hospital information system, 1985-1995. Le Groupe d'Epidemiologie
      Clinique du SIDA en Aquitaine (GECSA)].
AB  - OBJECTIVES: To describe the hospital-based information system developed by the
      GESCA (Clinical epidemiology group on AIDS in Aquitaine) and evaluate the main
      results obtained over the last 10 years, specifically data related to
      epidemiological monitoring, medico-economic analysis and clinical research in HIV
      infection. METHODS: Inclusion criteria were HIV-1 seropositivity confirmed by
      Western blot, age over 13 years, consultation or hospitalization is one of the 18
      participating units. Follow-up data were collected at each hospital visit.
      RESULTS: On December 31, 1995, 4268 subjects had been registered in the GECSA
      system, including 25.7% women. Contamination categories were homosexuals 33.4%,
      intravenous drug abusers 32.8%, heterosexuals 13.9%. A clear drop in the number
      of new cases in intravenous drug abusers and an increase in the number with
      heterosexual transmission was observed after 1988. The medico-economic analysis
      showed that patients followed in the system were in a more advanced stage at
      registry since 1992. More than half of the subjects are now taking antiretroviral
      therapy and prophylaxis for opportunistic infections. Clinically, after adjusting
      data for the major known prognosis factors, the risk of progression to AIDS is
      higher in homosexuals and intravenous drug abusers than in heterosexuals.
      Transmission route does not however have any significant effect on survival after
      development of AIDS. There is no significant difference in outcome of HIV
      infection between men and women and pregnancy is not associated with poorer
      outcome. CONCLUSION: This regional registry provides valuable data for
      epidemiological monitoring, medico-economic analysis, hospital management and
      clinical research.

PMID- 9183369
TI  - [Bilateral adrenal cysts and hepatorenal polycystic disease].
AB  - BACKGROUND: Cyst formation may occur in many localization in patients with
      polycystic renal disease. Adrenal gland cysts have not previously been reported.
      CASE REPORT: Hepatorenal polycystic disease was diagnosed in a 38-year-old man
      who underwent abdominal ultrasound examination for acute back pain. Subsequent
      computed tomography evidenced several cysts in both adrenal glands. DISCUSSION:
      Incidental discovery of cysts in the adrenal glands accounts for 4 to 22% of all
      cyst formations in this organ. Four types of cysts are observed: parasite cysts,
      epithelial cysts and adenomas, pseudocysts, and endothelial cysts. Appropriate
      treatment depends on the size of the cyst, the etiology context, and clinical
      manifestations. Treatment is indicated in case of symptomatic disease or when the
      ultrasound or CT-scan aspect is atypical.

PMID- 9183370
TI  - [Gene amplification: an important tool for predicting cytomegalovirus disease].

PMID- 9183371
TI  - [Cardiorespiratory arrest following ingestion of morphine sulfate in a patient
      with chronic renal failure].

PMID- 9183372
TI  - [Is prognosis in AIDS patients different in cases of cardiac involvement?
      Prospective study of 34 patients].

PMID- 9183373
TI  - [Organization of well-informed medical societies in France].

PMID- 9183374
TI  - [Necrotizing myelopathy after intrathecal methotrexate].

PMID- 9183375
TI  - [Mucoviscidosis. Nutritional management].

PMID- 9183376
TI  - [Mucoviscidosis. Antibiotic management].

PMID- 9183377
TI  - [Mucoviscidosis. Pulmonary transplantation].

PMID- 9183378
TI  - Comparison of inducible nitric oxide synthase gene expression and lung
      inflammation following intratracheal instillation of silica, coal, carbonyl iron,
      or titanium dioxide in rats.
AB  - The pulmonary toxicity of the respirable dusts silica, coal, carbonyl iron, and
      titanium dioxide on alveolar macrophage (AM) and neutrophil (PMN) inducible
      nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production was
      investigated. Rats were intratracheally instilled with 5 mg/100 g body weight of
      silica, coal, carbonyl iron, or titanium dioxide. The dust particles averaged
      less than 5 microns in diameter. Bronchoalveolar lavage was performed 24 h later.
      Bronchoalveolar lavage cell (BALC) differentials, iNOS gene expression and NO
      production by BALC (measured indirectly as NO-dependent chemiluminescence), and
      lavageable lung protein levels were measured. Analyzed on an equal mass basis,
      silica, coal, and titanium dioxide dusts increased the production of iNOS
      dependent NO by AM. Silica and titanium dioxide both increased the levels of iNOS
      mRNA while carbonyl iron and coal did not. Each dust caused an increase in PMN,
      indicating an inflammatory response. Carbonyl iron and titanium dioxide decreased
      the numbers of AM. Levels of acellular lavageable lung protein were increased by
      silica, carbonyl iron, and titanium dioxide. When exposure was normalized for an
      equal number of particles, the pneumotoxic dusts, silica and coal, caused more
      inflammation and NO production than the nuisance dusts, carbonyl iron and
      titanium dioxide. Therefore, it appears that particle number is a more
      appropriate metric of exposure than mass when comparing the relative
      pathogenicity of dusts of different sizes. Furthermore, since the potency of
      these dusts (on a particle number basis) to increase iNOS gene expression
      reflects their inflammatory and pathogenic potential, it is proposed that NO may
      contribute to the early inflammatory damage observed in the lung following dust
      exposure.

PMID- 9183379
TI  - Chronic ultraviolet exposure-induced p53 gene alterations in Sencar mouse skin
      carcinogenesis model.
AB  - Alterations of the tumor suppresser gene p53 have been found in ultraviolet
      radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors.
      However, links between p53 gene alterations and the stages of carcinogenesis
      induced by UVR have not been clearly defined. We established a chronic UVR
      exposure-induced Sencar mouse skin carcinogenesis model to determine the
      frequency of p53 gene alterations in different stages of carcinogenesis,
      including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and
      malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were
      found in this model. Positive p53 nuclear staining was found in 10/37 (27%) of
      SCCs and 12/24 (50%) of SCTs, but was not detected in normal skin or papillomas.
      DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and
      tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by
      using nested polymerase chain reaction (PCR). Subsequent single-strand
      conformation polymorphism (SSCP) assay and sequencing analysis revealed one point
      mutation in exon 6 (coden 193, C-->A transition) from a UV-exposed skin sample,
      and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C-
      >T, two C-->A, one C-->G, and one A-->T transition, respectively) from four SCTs,
      two SCCs and one UV-exposed skin sample. These experimental results demonstrate
      that alterations in the p53 gene are frequent events in chronic UV exposure
      induced SCCs and later stage SCTs in Sencar mouse skin.

PMID- 9183380
TI  - Differential induction of polyamine oxidase activity in liver and heart of iron
      overloaded rats.
AB  - The present study was undertaken to investigate the effect of iron dextran
      treatment on polyamine oxidase (PAO) activity, iron accumulation, and lipid
      peroxidation in livers and hearts of rats. PAO catalyzes oxidative deamination of
      polyamines, the cellular aliphatic cations. This reaction produces highly toxic
      hydrogen peroxide, 3-acetamidopropanal, and precursors of higher polyamines. The
      rats were given iron dextran daily for 7 d. In iron-dextran-treated rats, a
      marked increase in the hepatic level of iron was associated with enhanced lipid
      peroxidation and increased PAO activity. Though iron accumulation and lipid
      peroxidation in the iron-treated rats increased significantly in the heart, PAO
      activity remained unchanged. The paraffin sections of livers stained with Perls
      iron stain showed the presence of iron in macrophages and hepatocytes. The
      sections of hearts showed iron deposits only in macrophages, while myocytes
      showed no iron staining. These results show that although iron dextran treatment
      results in accumulation of iron in both liver and heart, it induces PAO activity
      only in liver. The significance of increased PAO activity in lipid peroxidation
      and fibrosis in iron-mediated injury is discussed.

PMID- 9183381
TI  - Influence of different degrees of reduced renal mass on the renal and hepatic
      disposition of administered cadmium.
AB  - The present study was designed to evaluate, in rats, the effect of varying
      degrees of reduced renal mass on the disposition of administered cadmium. As part
      of this evaluation, the intrarenal, hepatic, and hematological disposition of
      cadmium and the urinary and fecal excretion of cadmium were studied and
      characterized in control, uninephrectomized (NPX), and 75% nephrectomized (75%
      NPX) rats 1 d, 2 d, and 7 d after the intravenous injection of a nonnephrotoxic
      8.9 mumol/kg dose of cadmium chloride. Renal accumulation of cadmium, especially
      in the cortex and outer stripe of the outer medulla, was reduced significantly in
      the 75% NPX rats, but not in the NPX rats, between d 2 and 7 after the injection
      of cadmium. The diminution in the renal accumulation of cadmium in the 75% NPX
      rats was most likely due to diminished glomerular filtration rate and renal
      clearance of cadmium induced by 75% nephrectomy. Despite reduced glomerular
      filtration rate, the cumulative urinary excretion of cadmium in the 75% NPX rats
      was significantly greater than that in either the NPX rats or the control rats.
      It should be mentioned, however, that very little of the administered dose of
      cadmium was excreted in the urine by any of the three groups of rats.
      Interestingly, the content of cadmium in the liver was significantly greater in
      75% NPX rats than in NPX or control rats between d 1 and 7 after the injection of
      cadmium. Moreover, the 75% NPX rats excreted significantly less cadmium in the
      feces over the 7 d of study than did the other 2 groups of rats, indicating that
      75% nephrectomy causes a significant alteration in one or more of the mechanisms
      involved in the fecal excretion of cadmium. In summary, the findings from the
      present study indicate that the renal and hepatic handling of administered
      cadmium in rats changes significantly when renal mass is reduced by 75%. Further
      studies are needed to better characterize the effects of reductions of renal
      mass, which impair renal function significantly, on both the disposition and
      toxicity of cadmium in renal and hepatic tissues.

PMID- 9183382
TI  - Subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl in rats.
AB  - The subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl (PCB 128) was
      investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for
      13 wk. The growth rate was not affected by treatment and no apparent clinical
      signs of toxicity were observed. There was a significant increase in liver weight
      in the 50 ppm females. The liver ethoxyresorufin deethylase (EROD) activity was
      increased by five- and fourfold in the highest dose males and females,
      respectively, while aminopyrine demethylase (ADPM) activity was significantly
      increased only in the highest dose females. Liver vitamin A was significantly
      reduced in the highest dose females. No other biochemical or hematological
      effects were observed. Treatment-related histopathological changes were seen in
      the thyroid and liver, and to a lesser extent in the bone marrow and thymus.
      Residue data showed a dose-dependent accumulation of PCB 128 in the following
      tissues: fat, liver, kidney, brain, spleen, and serum, with the highest
      concentration being found in fat followed by liver and kidney. Based on these
      data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm
      in diet or 42 micrograms/kg body weight.

PMID- 9183384
TI  - 68th Meeting of the European Atherosclerosis Society. Molecular Cell Biology and
      Atherogenesis. Brugge, Belgium, 7-10 May 1997. Abstracts.

PMID- 9183385
TI  - British Society of Audiology short papers meeting on experimental studies of
      hearing and deafness. Cambridge, United Kingdom, 22-23 September 1996. Abstracts.

PMID- 9183386
TI  - European Society of Gynaecological Oncology, 10th International Meeting. Coimbra,
      Portugal, 26 April-2 May 1997. Abstracts.

PMID- 9183383
TI  - Influence of dietary selenium on the disposition of arsenate in the female B6C3F1
      mouse.
AB  - Interactions between arsenic (As) and selenium (Se) at the metabolic level are
      multifaceted and complex. These interactions are of practical significance
      because populations in various parts of the world are simultaneously exposed to
      inorganic As in drinking water and Se mainly in the diet at varying levels. The
      primary goal of this study was to investigate whether differing dietary Se status
      would alter the profile of urinary metabolites or their time course for
      elimination after exposure to arsenate [As(V)]. Weanling female B6C3F1 mice were
      maintained for 28 d on either a control diet of powdered rodent meal sufficient
      in Se (A, 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se),
      sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then
      received by oral gavage 5 mg (As)/kg as sodium [73As] arsenate. The time course
      for elimination of total arsenic and metabolites in urine was measured over a 48
      h period, and total arsenic was determined in feces and tissues at 48 h. Mice on
      the Se excess diet excreted a significantly higher percentage of urinary As as
      inorganic As, with a significantly decreased ratio of organic to inorganic As
      compared to Se-sufficient mice, suggesting that As methylation was decreased.
      Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and
      dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however,
      further studies are required to confirm this finding. Mice on the Se-sufficient
      meal diet (A) excreted significantly less (by percent) arsenate-derived
      radioactivity in urine and more in feces compared to mice on the Se-sufficient
      TYB diet (C), with total elimination being similar for both groups. This
      indicates that mice on the meal diet absorbed significantly less As(V) than mice
      on the TYB diet, and this may be due to more fiber or "bulk" in the meal diet.
      This finding emphasizes the importance of considering dietary composition when
      interpreting and comparing As disposition studies. Overall this study provides
      suggestive evidence that dietary Se status alters As metabolism and disposition.
      This indicates that dietary Se status may be an issue that should be considered
      in the design and interpretation of epidemiologic studies.

PMID- 9183388
TI  - 51st Annual meeting of the Canadian Society of Otolaryngology-Head and Neck
      surgery. Whistler, British Columbia, June 22-25, 1997. Abstracts.

PMID- 9183387
TI  - Congress on In Vitro Biology. 1997 Meeting of the Society for In Vitro Biology.
      Washington, DC, June 14-18, 1997. Abstracts.

PMID- 9183389
TI  - Proceedings of the Physiological Society. Dublin, 24-26 March 1997.

PMID- 9183390
TI  - The 3rd International Congress of the Osteoarthritis Research Society.
      Osteoarthritis in focus: etiopathogenesis, assessment, and treatment. Singapore,
      7-9 June 1997. Abstracts.

PMID- 9183391
TI  - Trends in Neuroprotective Drugs: Design, Pharmacology and Clinics. International
      Conference. Riga, Latvia, May 29-June 1, 1997. Abstracts.

PMID- 9183393
TI  - [Determinants of malignant vasovagal syncopes with asystole disclosed by the
      tilting test and therapeutic implications].
AB  - In order to evaluate the determinants of malignant vasovagal syncope with
      asystole revealed by the tilting test and to determine the possible therapeutic
      implications, 179 patients (91 women and 88 men, mean age 36.6 +/- 20.1 years)
      referred for the assessment of unexplained a were studied. The test was performed
      with a tilt of 60 degrees for 45 minutes. A bolus of isoprenaline (0.02 to 0.08
      microgram/kg.min) was injected in the case of a negative passive test. Asystole
      was defined as a ventricular pause lasting > or = 5 seconds. RESULTS: Ten (13%)
      of the 77 patients with a positive tilting test experienced a cardio-inhibitory
      reaction with prolonged asystole lasting an average of 11.9 +/- 4.9 seconds.
      Compared to the other 67 patients with a positive test, those with asystole were
      younger (23/9 +/- 14.8 years vs 32.9 +/- 18.5 years, NS) and had a more frequent
      history of convulsions (6/10 vs 9/67, p = 0.05) during spontaneous episodes and
      trauma (9/10 vs 27/67, p = 0.005). Implantation of a pacemaker was chosen first
      line treatment for the first 6 patients. Their follow-up tilting tests remained
      positive (pre S = 4, S = 1) despite DDD stimulation of 45 bpm. Five of these
      patients and the following 4 patients were retested under beta-blockers. In six
      patients treated with beta-blockers, the clinical symptoms resolved completely (n
      = 3) or improved (n = 3), in contrast with 3 other patients in whom the tilting
      test remained positive with recurrence of asystole. The mean follow-up for the
      169 patients is 22.7 +/- 11 months and the ten patients with asystole remained
      totally asymptomatic. CONCLUSION: An asystolic response during the tilting test
      is characteristic of vasovagal syncope described as malignant. The syndrome
      essentially affects young patients, with a more frequent history of trauma and
      convulsions. Beta-blockers appear to be at least as effective as permanent
      pacemaker to prevent symptoms in this specific subgroup.

PMID- 9183392
TI  - [Influence of anti-arrhythmia agents on heart rate variability].
AB  - Since analysis of heart rate variability (HRV) is able to identify subjects at
      risk of sudden death and as antiarrhythmics can interfere with this prognosis,
      the objective of this study was to determine whether antiarrhythmics (AA)
      modified the HRV measured on a 24-hour Holter recording and after rapid
      ventricular stimulation and whether the initial HRV and its possible modification
      during treatment with AA were correlated with the results of AA treatment in
      patients with ventricular tachycardia (sustained VT). The HRV was studied in 50
      patients with heart disease and spontaneous sustained VT, reproduced by
      programmed ventricular stimulation. This analysis was performed at baseline with
      antiarrhythmic treatment consisting of low-dose beta-blocker and quinidines in 26
      patients (group I) or amiodarone in 24 patients (group II). Treatment was
      effective (i.e. prevented induction of VT) in 9 patients in group I (group la)
      and 5 patients in group II (group IIa). Treatment was ineffective in the other 17
      patients of group I (group Ib) and 19 patients of group II (group IIb). The
      initial HRV was similar in the patients of groups Ia and Ib or groups IIa and
      IIb. Temporal analysis did not reveal any significant variation of HRV during AA
      treatment. In contrast, spectral analysis of HRV and the HRV observed during
      ventricular stimulation demonstrated a significant reduction of this parameter (p
      < 0.05 for groups I and II combined). IN CONCLUSION: the initial HRV is not
      predictive of the results of treatment. Quinidines and amiodarone tend to
      decrease HRV regardless of the effect of the AA on the prevention of VT.

PMID- 9183395
TI  - [Transesophageal echographic demonstration of ulcerated atheromatous plaques of
      the thoracic aorta responsible for cholesterol emboli].
AB  - The authors present of case of a 61-year-old man suffering from cholesterol
      emboli, in whom transoesophageal echocardiography revealed complex atheromatous
      lesions of the thoracic aorta. There is growing emphasis, at the present time, on
      the concept of triggering factors with the multiplication of endovascular
      radiological investigations, the more widespread availability of cardiac surgery
      and the use of anticoagulants and fibrinolytics. The prognosis is poor, treatment
      is only palliative and preventive measures are therefore essential.

PMID- 9183394
TI  - [Deep venous thromboses and occult cancers].
AB  - The association between venous thrombosis and cancer has been known for a long
      time. Thrombophlebitis often occurs during the course of a known cancer, but
      sometimes constitutes the presenting sign. Based on a series of 10 cases of deep
      venous thrombosis (DVT) revealing an underlying cancer, the authors analyse the
      various aspects of this association and the elements which help to guide the
      diagnosis towards a cancer. A simple assessment comprising clinical examination,
      full blood count and differential white cell count, erythrocyte sedimentation
      rate, protein electrophoresis, chest x-ray and abdomino-pelvic ultrasonography
      was performed on admission in 75 cases of presumably idiopathic DVT and revealed
      a cancer in 10 cases: 6 women and 4 men with a mean age of 53 years. Cancers were
      located in the urogenital tract in 5 cases, in the bronchi in 2 cases, in the
      stomach in one case, and there was one case of acute myeloblastic leukaemia (AML)
      and another case of liposarcoma of the left iliac fossa. The histological type
      most frequently encountered was adenocarcinoma in 6 cases. In 9 out of 10 cases,
      the cancer was discovered at the stage of metastases. However, a localized cancer
      was detected in one case, in which surgical treatment allowed cure of the
      patient. Comparison of the various characteristics of DVT between the group of
      DVT revealing a cancer and the group of DVT which remained idiopathic did not
      reveal any statistically significant difference. A simple, inexpensive assessment
      looking for a cancer must be systematically performed in all cases of idiopathic
      DVT in patients between the ages of 50 and 85 years. Other more elaborate
      examinations may be requested on the basis of the results of the preliminary
      assessment.

PMID- 9183396
TI  - [Angiographic course over 10 years of giant aneurysm of the circumflex artery].
AB  - Pathological dilatations of the coronary arteries are not exceptional and are
      called megadolichoartery, aneurysm or ectasia. Cases of marked arterial
      dilatation, although much rarer, are regularly reported following their discovery
      due to the impressive angiographic, echocardiographic or autopsy findings.
      However, their course, particularly in the long term, remains unclear. The
      authors report the case of a patient with a very large spindle-shaped aneurysm of
      the circumflex artery whose course was able to be followed over a period of ten
      years on three successive angiographic assessments performed for clinical
      coronary events. This follow-up was dominated by thrombosis of the aneurysm,
      extension of the aneurysmal disease and severe deterioration of left ventricular
      function.

PMID- 9183397
TI  - [Complicated hydatid cyst of the right atrium simulating myxoma of the tricuspid
      valve].
AB  - The authors report the case of a 6-year-old girl with multi-organ hydatid
      disease, revealed by a complication: hydatid cyst of the right atrium. They
      emphasize the latency and clinical polymorphism of right cardiac sites of hydatid
      cyst and the severity of its prognosis. The particular site of this right atrial
      tumour and its relations with the septal leaflet of the tricuspid valve could be
      confused, on echocardiography, with myxoma of the tricuspid valve. The aetiology
      in this case was confirmed at surgery.

PMID- 9183398
TI  - [Quantification of mitral insufficiency in color Doppler by studying the
      convergence zone].
AB  - Many in vitro and in vivo studies have recently emphasized the value of analysis
      of the colour Doppler convergence zone for quantification of mitra insufficiency.
      This approach provides an estimation of the maximal instantaneous regurgitation
      flow rate, the area of the regurgitating orifice, the volume regurgitated with
      each beat and the regurgitation fraction. After a brief review of fluid
      mechanics, this review of the literature with be focus on the principle, results,
      advantages and limitations of this method.

PMID- 9183399
TI  - [Are small and thin people condemned to an early death? Scotland Yard inquiry].

PMID- 9183400
TI  - [Intestinal stenosis during ulceronecrotizing enterocolitis].
AB  - BACKGROUND: Intestinal stenosis following necrotizing enterocolitis (NE) occurred
      both in surgically-treated neonates after perforation, distal to an enterostomy
      and in medically-treated patients developing symptoms of obstruction. It has been
      proposed to detect stenosis by contrast enema before refeeding in those medically
      treated patients. The aim of this study was to compare delay, clinical and
      pathological characteristics of surgical and medical patients, both after
      occlusion and prospective contrast studies. PATIENTS AND METHODS: Fifteen
      patients out of 50 with NE observed from 1984 to 1994 developed one or several
      intestinal stenosis. Diagnosis of NE was based on usual clinical signs, X-ray
      pneumatosis (43 to 50) and/or perforation in 16 cases. Among these 16 surgical
      patients, 12 survived the initial perforation. Among the 34 medical patients, 11
      were seen before 1989 and did not have contrast studies before refeeding; 23 seen
      after 1989 had a contrast enema before. RESULTS: One or several stenosis occurred
      in four out of 12 surgical patients, four out of 11 medical patients without
      prospective contrast studies (one of them died from sepsis) and seven out of the
      23 of the prospective group. On the whole, 26 stenosis occurred in 15 neonates:
      ten to the right colon, five to the transverse and 11 to the left colon. One
      ileal stenosis followed enterostomy. Delay of stenosis development was comparable
      in the three groups (between 3 weeks and 3 months). Pathologic examination showed
      similar lesions in the three groups (fibrosis 15, edema nine to 15 and chronic
      inflammation 12 to 15). CONCLUSION: Among 46 neonates who survived the initial
      period, 15 developed stenosis, a 30% proportion similar in patients operated on
      for perforation or in medically-treated patients whose diagnosis was made after
      occlusion or after contrast enema as well. These results suggest that systematic
      stenosis detection by contrast enema may avoid complications and permit
      programmed one-stage surgery.

PMID- 9183401
TI  - [Type of birth center and conditions of transfer of neonates under 1500 g or
      gestational age under 33 weeks].
AB  - BACKGROUND: Perinatal care's organization has been widely discussed in France
      during this last decade. Until now, transfer of high-risk neonates from their
      birth maternity to a pediatric unit using mobile vehicles led by specialized
      teams is encouraged in this country. POPULATION AND METHODS: Retrospective
      analysis of the type of maternities of birth for a population of 717 newborns,
      weighing less than 1,500 g and/or of gestational age under 33 weeks, extracted
      from a sample of 84,279 births in 1991. RESULTS: Only 15.6% of studied births
      took place in a maternity including a special intensive care pediatric unit
      (international level 3); 58.7% of those newborns where transferred outborn. There
      was a significant difference between the immediate access of newborns to a level
      3 pediatric unit according to the location-of birth: significantly fewer newborns
      were directly transferred to a level 3 unit when born in a facility that included
      a level 2 pediatric unit, compared with those born in facilities that included a
      level 1 or 3 pediatric unit. CONCLUSION: Strong efforts should be made to
      identify mothers at high risk of giving birth to extremely prematured babies or
      babies with a very low birthweight so that births could take place in maternities
      properly equipped for their care. Perinatal care's organization should be built
      on a hierarchical network of maternities and pediatric services related to the
      risk of the population. Accreditation of maternities and pediatric services could
      help moving towards this kind of organization.

PMID- 9183402
TI  - [Neonatal esophago-gastro-duodenoscopy. Apropos of 123 examinations performed on
      107 newborn infants].
AB  - Upper gastrointestinal endoscopy is frequently used in the neonatal period. The
      aim of this study was to assess the frequency of the different lesions occurring
      as well as to precise indications of upper gastrointestinal endoscopy in
      neonates. POPULATION AND METHODS: A retrospective study including 107 neonates
      referred between October 1986 and April 1995 has been achieved in the pediatric
      gastroenterology unit of the Lille University Hospital. Various factors were
      analysed: gestational age, sex, reasons for endoscopy and macroscopic lesions
      observed. Three groups were constituted according to macroscopic findings; group
      I: normal aspect (n = 22); group II: isolated esophagitis (n = 27); group III:
      esogastritis or gastroduodenitis or esogastroduodenitis (n = 38). Chi 2 test was
      performed for statistical analysis. RESULTS: Signs recalling esophagitis (cry
      during feeding) were more frequent in group II than in group III: 37% vs 13% (P <
      0.03). The neonates undergoing endoscopy for life-threatening events were more
      frequent in group I than in group II or III, respectively: 59% vs 15% (P < 0.01)
      and 59% vs 8% (P < 10(-4). Upper gastrointestinal endoscopy led to a precise
      diagnosis in 80% of the neonates. However 95% of those examined for hematemesis
      presented macroscopic lesions. CONCLUSIONS: Hematemesis and suspicion of
      esophagitis are good indications for upper gastrointestinal endoscopy in neonatal
      period. In life-threatening events and suspicion of pyloric stenosis, upper
      gastrointestinal endoscopy is only complementary of more contributive other
      examinations.

PMID- 9183403
TI  - [Otorrhea on transtympanic aerator].
AB  - BACKGROUND: Purulent otorrhea is the most common complication of tympanostomy
      tubes. POPULATION AND METHODS: Results of culture of otorrhea in 33 consecutive
      cases were compared to two similar studies performed 4 and 8 years ago in the
      same institution. RESULTS: The most frequent organisms were Pseudomonas
      aeruginosa, Haemophilus influenzae, Staphylococcus aureus and Streptococcus
      pneumoniae (45, 24, 21 and 15% of the cases, respectively). Such flora resembles
      that of external otitis and chronic otitis media (P aeruginosa and S pneumoniae).
      CONCLUSION: Sensitivity of the organisms encountered in these otorrheas favors
      the use of topical drops rather than oral antibiotics as the first choice of
      treatment.

PMID- 9183405
TI  - [Value of in vitro study of osteoclast precursors in the case of severe infantile
      osteopetrosis treated by bone marrow graft].
AB  - BACKGROUND: Pathogenesis of osteopetrosis is still debated. Testing the ability
      of osteoclastic progenitors to support the proliferation of functional cells may
      be useful in understanding pathogenesis. CASE REPORT AND METHODS: A diagnosis of
      osteopetrosis was made in a girl 1 month-old, born to consanguuineous parents.
      Bone marrow transplantation was uneffective at the age of 3 months but a second
      engraftment was successful at 5 months. Unfortunately, the patient died from
      severe thrombocytopenia at the age of 8 months. Long-term cultures of
      mononucleated cells from the patient's blood were performed before and after the
      bone marrow transplantation, with or without growth factors such as vitamin D3,
      IL-6 and IL-1. Similar studies were made from the patient's marrow obtained after
      transplantation; all results were compared with those obtained after culturing
      control cells from cord blood umbilical. RESULTS: Production of osteoclastic
      cells was mild in peripheral blood cultures; it was important in bone marrow
      cultures in presence of growth factors. CONCLUSION: These results suggest that
      osteopetrosis in our patient resulted from an intrinsic defect in progenitors of
      osteoclasts.

PMID- 9183404
TI  - [Maternofetal disseminated candidiasis and high-grade prematurity].
AB  - BACKGROUND: Despite the frequency of vaginal yeast colonization, serious
      candidiasis infections in pregnant patients or neonates remain rare. Four cases
      of disseminated congenital candidiasis in very preterm infants are reported. CASE
      REPORTS: Congenital Candida albicans infection has been diagnosed in four very
      preterm infants. In three cases, the mothers had intrauterine devices in place
      throughout pregnancy. A careful macroscopic examination of the umbilical cord and
      placenta after birth has allowed an early management strategy in three cases. In
      all cases, a serious infectious alveolitis occurred. A pronounced increase in
      white blood cells (> 50,000/mm3) and high levels of both segmented neutrophil and
      band cells, despite the frequent normality of the CRP, constituted other
      features. Infection was controlled by parenteral amphotericin B or fluconazole.
      In one case, serious thrombocytopenia occurred after the first amphotericin B
      injection requiring substitution for fluconazole. The outcome was unfavourable in
      two cases with an extensive periventricular leukomalacia. CONCLUSION: Congenital
      candidiasis in these four very preterm neonates has several features in common:
      intrauterine contraceptive device during pregnancy, characteristic
      chorioamnionitis and funisitis, high WBC count, infectious alveolitis.
      Fluconazole as alternative to amphotericine B therapy is proposed.

PMID- 9183406
TI  - [Neonatal alloimmune thrombopenia in anti-HPA-3a (Baka) immunization].
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) in the HPA-3a system is
      responsible for less than 5% of all cases of NAIT. CASE REPORT: Thomas, a male
      infant, was born at 39 weeks of gestation after an uncomplicated pregnancy.
      Delivery was normal. The Apgar score was 9 at 1 minute, and 10 at 5 and 10
      minutes. At 1 hour of age, he displayed extensive petechiae and purpura over the
      back. The platelet count was 8,000/mm3. Hematesis and extensive petechiae were
      noted, leading to an exchange transfusion followed by a transfusion of 0.5 U/kg
      of random donor platelets, 0.4 g/kg/d of intravenous immunoglobulin (IVIg) and 10
      mg/kg/d of corticosteroids. IVIg were discontinued on d5 and corticosteroids on
      d10. There was no relapse of thrombocytopenia. A neonatal alloimmune
      thrombocytopenia with an HPA-3a (Baka) incompatibility was confirmed. CONCLUSION:
      HPA-3a incompatibility is certainly more frequent than the rare cases reported
      and must be searched for in all cases of neonatal thrombocytopenia.

PMID- 9183407
TI  - [Spontaneous neonatal arterial thrombosis treated with tissue plasminogen
      activator].
AB  - BACKGROUND: Spontaneous neonatal arterial thrombosis is a rare entity with
      serious and potentially fatal complications. A wide spectrum of management has
      been proposed. CASE REPORT: Ophelie was born after premature delivery at 33
      weeks. She was referred soon after birth in the neonatal intensive care unit for
      respiratory distress syndrome. Spontaneous acute ischemia of the right lower limb
      was noted soon after admission. Iliac thrombosis was confirmed by ultrasonography
      and colour coded doppler. Thrombolysis was achieved with systemic infusion of
      recombinant tissue plasminogen activator (rtPA). Full recovery was obtained
      within 12 hours of treatment without any complication. No rethrombosis occurred
      with heparin prophylaxis. No predisposing disorder to thrombosis was found.
      CONCLUSION: Systemic rtPA is an alternative to thrombectomy and urokinase in
      critically ill neonates. This treatment should be considered if no major risk of
      bleeding is found during the pretherapeutic screening.

PMID- 9183408
TI  - [Clostridium perfringens meningitis with fatal outcome in a 3-week old infant].
AB  - BACKGROUND: Clostridium perfringens meningitis is a rare condition usually
      associated to skull injuries, surgery or gastro-intestinal disorders. CASE
      REPORT: A 21 day-old infant was admitted for the sudden worsening of a neonatal
      post-hemorrhagic hydrocephalus. Eighteen hours after admission, she developed a
      septic status with acute meningitis. A CT scan revealed the presence of
      intracerebral gas suggesting the responsibility of an anaerobic bacterium. The
      infant died within 24 hours from multiorgan failure, hemodynamic disorders, acute
      anemia with red urines. Clostridium perfringens was isolated both from the blood
      and CSF. CONCLUSIONS: The tissue alterations following meningeal hemorrhage may
      favor anaerobic growth. The presence of intracerebral gas is highly suggestive of
      the diagnosis. The prognosis is very poor.

PMID- 9183409
TI  - [Hypercalciuria: etiologies and treatment].
AB  - Hypercalciuria is a rare biological symptom with multiple possible etiologies in
      children. Normal calcium excretion rate in children is defined as lower than 4
      mg/kg per day, significantly higher values being observed in infants. When using
      urinary calcium: creatinine ratio, normal values are below 0.22 mg/mg in
      children, and below 0.6 to 0.8 mg/mg in infants. In our experience half patients
      with hypercalciuria have idiopathic hypercalciuria. Idiopathic hypercalciuria can
      be hereditary with a dominant autosomal mode of inheritance. Its pathophysiology
      is unclear, increased calcium intestinal absorption and impaired renal tubular
      calcium reabsorption being the two main underlying anomalies. Patients with
      hypercalciuria should be informed about the risk of urolithiasis and its possible
      prevention by a high water intake. In those patients with nephrocalcinosis or
      recurrent episodes of lithiasis, hydrochlorothiazide can be effective in reducing
      hypercalciuria. However, adverse effects of hydrochlorothiazide on serum lipids
      have been recently reported and make this treatment questionable in the long
      term.

PMID- 9183410
TI  - [Long-term consequences of fetal nutrition].
AB  - A large number of animal experimental data indicate that pre- or early postnatal
      malnutrition can have long-term negative consequences on weight and height, with
      smaller weight and height in adulthood than predicted on genetics basis.
      Furthermore, according to the Barker's hypothesis, based on data available from
      British cohort studies, in utero malnutrition could also result in an increased
      risk of cardiovascular, endocrine and metabolic diseases in adulthood. There are
      however discordant data in the literature which invite to be cautious about on
      this hypothesis, mainly because the role of the socio-economic factors during
      childhood and adulthood have not been taken into account.

PMID- 9183411
TI  - [Radiological case of the month. Neonatal hepatic hemangioendothelioma].

PMID- 9183412
TI  - [Radiological case of the month. Gaucher's disease: ischemic necrosis of the
      femoral head].

PMID- 9183413
TI  - [Protein requirements of healthy infants and children. Comite de nutrition de la
      Societe francaise de Pediatrie].
AB  - The protein requirements during infancy and childhood are the sum of both
      maintenance nitrogen needs and the amount of nitrogen required for growth.
      Exclusive breast feeding entirely meets these requirements, at least until 6
      months of age, and the different approaches for estimating protein needs provide
      consistent values, which are strikingly steady for the first 12 months. From the
      mean protein requirement, it is possible to calculate the safe protein intake,
      eg, the amount of protein which should meet the requirements of every infant and
      child from 4 months to 3 years of age. Several expert committees concluded that
      the safe intake amounts to 15 g/d, a figure which now seems overestimated. In any
      case, the average intake of infants and toddlers is two to three fold higher than
      the safe protein intake in most developed countries. This holds true during later
      childhood and adolescence, the intakes exceeding the needs so much as to render
      pointless any discussion about amino acid requirements. Although the information
      about the long term effects of protein intakes in excess of the needs is scanty,
      the tight relationship between protein and fat intakes, particularly saturated
      ones, should not be overlooked and should prompt some caution when providing
      mothers with recommendations about feeding their infant.

PMID- 9183414
TI  - [Atypical clinical manifestation in a child with parvovirus B19 infection].

PMID- 9183415
TI  - [Cytomegalovirus infection and pregnancy].

PMID- 9183416
TI  - [Application of EMLA cream without an adhesive film].

PMID- 9183417
TI  - [Serological study of the incidence of Helicobacter pylori infection in
      institutionalized children with brain diseases].

PMID- 9183418
TI  - [The 150th anniversary of of he birth of anesthesia].

PMID- 9183419
TI  - [Epidural anesthesia in children under 3 months of age. Apropos of 49 cases].
AB  - This retrospective study includes 45 patients (age: 32 +/- 28 days; weight: 4,077
      +/- 988 g) who underwent epidural analgesia with a catheter for various surgical
      operations. Epidural space was detected by the loss of resistance to air
      technique. The anaesthetic solution administered was bupivacaine 0.25% with
      1/200,000 epinephrine. Four technical failures were recorded; intraoperative
      analgesia was adequate for all other patients. In 17 patients, postoperative
      analgesia was maintained by continuous infusion (0.125% bupivacaine or 0.25%
      lidocaine: 0.2 mL.kg -1.h-1). In 18 patients, it was managed by iterative
      injections (0.25% bupivacaine with epinephrine: 0.25 mL.kg -1.h-1). In 10
      patients, a single shot was sufficient. Postoperative analgesia was found to be
      inadequate in four patients. No incidents or accidents were recorded. A benefit
      risk analysis with the support of the literature attempts to define the main
      indications of this method.

PMID- 9183420
TI  - [Is early extubation after surgery for esophageal cancer possible?].
AB  - In a series of 50 patients undergoing elective oesogastrectomy through a
      laparotomy and a right thoracotomy, the avoidance of overnight ventilatory
      support was made possible by the agreement of anaesthetists and surgeons on
      suitable policies. The attempt to extubate the patients immediately
      postoperatively differentiated two groups. For the first group (32 patients;
      64%), early extubation could be performed and only one patient was reintubated
      and required prolonged ventilation. A second group comprised 18 patients who
      could not be extubated early (36%). For most of the patients in this second group
      extubation was only delayed until the next day, and recovery was otherwise
      uneventful. In three cases, however, pulmonary atelectasis with infection was a
      major problem, and these patients required broncho-endoscopies, and prolonged
      ventilatory support. Nevertheless, morbidity and mortality after oesophagectomy
      were significantly reduced in this series, compared with a previous study in the
      same hospital. Careful postoperative assessment of the patient is essential. The
      main factors leading to the decision for early extubation appeared to be: absence
      of serious cardiovascular history, absence of peroperative surgical
      complications, adequate rewarming, normal chest X-ray, and the presence of
      clinical criteria for extubation along with adequate arterial blood gases. If the
      above criteria can be achieved, then early extubation should be routine and can
      be safely performed in the majority of cases.

PMID- 9183421
TI  - [Intra-articular analgesia after arthroscopy of the knee].
AB  - In 33 patients the authors compared two protocols for postoperative analgesia
      after elective arthroscopy of the knee. One group (n = 11) received plain
      bupivacaine 0.25% by intra-articular administration. Another group (n = 11)
      received by the same route a mixture of bupivacaine 0.25% with fentanyl 50
      micrograms. The last group (placebo group: n = 11) received the same volume of
      saline. The combination of bupivacaine with fentanyl reduced postoperative pain
      more effectively than plain bupivacaine and the analgesic effect was still
      present 9 hours after the arthroscopy.

PMID- 9183422
TI  - [Evaluation of 2 dosages of fentanyl in caudal anesthesia. A prospective
      randomized double-blind study].
AB  - A caudal block is currently performed in children. A randomized and double blind
      study including two dosages of fentanyl: 0.5 microgram.kg-1 (group I) and 1
      micrograms.kg-1 (group II) in association with bupivacaine 0.25% at a dosage of 1
      mL.kg-1 was carried out. Two groups of 25 children undergoing urogenital or
      orthopaedic surgery participated in this study. Analgesia and side effects were
      evaluated 24 hours postoperatively. Quality and duration of analgesia were
      similar in the two groups. Furthermore, recovery of anaesthesia was rapid and
      calm. The frequency of nausea and vomiting was respectively 24% and 20% in groups
      I and II and did not require any specific therapy. Therefore it appears that
      caudal block with bupivacaine 0.25% and fentanyl 0.5 microgram.kg-1 is a very
      satisfactory technique in children when indicated.

PMID- 9183423
TI  - [Clinical, therapeutic and developmental aspects of acute bronchiolitis in
      Tunisia].
AB  - Fourteen infants with severe acute bronchiolitis were admitted to the Intensive
      Care Unit (ICU) of Tunis. This pathology represents 36% of severe
      bronchopulmonary infections admitted to this ICU. Their age ranged between 2 and
      48 weeks (mean: 15 weeks). Eight infants had hypotrophy. Two infants had
      congenital heart disease and one infant had tracheo-bronchomalacia. Viruses were
      found in 6/11 patients. Respiratory syncytial virus (RSV) was identified in five
      patients and an adenovirus in one patient. Five patients had respiratory arrest
      at ICU admission. Ten infants had evidence of atelectasis on chest X-ray films.
      Thirteen patients required mechanical ventilation. One infant had inappropriate
      antidiuretic hormone secretion resulting in convulsions. One infant had
      supraventricular tachycardia. Both had RSV infection. One patient who had
      congenital heart disease and RSV infection died. In the other 12 patients
      receiving mechanical ventilation, the mean duration of ventilation was 9 days
      (range: 2-30 days). The second patient who had congenital heart disease and RSV
      infection had severe respiratory sequelae at discharge.

PMID- 9183424
TI  - [Prolonged curarization after administration of mivacurium].

PMID- 9183425
TI  - [Chatergee syndrome and anesthesia. Apropos of a case].
AB  - A combination of complete left bundle branch block (LBBB) and symmetrical
      negative T waves on the ECG characterizes the Chattergee syndrome. This pattern
      is infrequently and fortuitously detected in the absence of clinical symptoms.
      However, when appearing during general anaesthesia, it may lead to diagnostic
      difficulties to rule out a myocardial ischaemia. One case of this pattern was
      observed near the end of an otherwise non-complicated cholecystectomy in a ASA II
      45 year old man, ECG abnormalities lasted for only a short time. Recovery and
      outcome were uneventful. Investigations were negative except for an early LBBB
      during the exercise test. Echocardiography and coronarography were normal. No
      therapy was given. In such perioperative cases, it is recommended to keep a very
      cautious attitude and to search for an incipient coronary disease which cannot be
      completely excluded in some cases.

PMID- 9183426
TI  - [Should we give up combining spinal anesthesia and anticoagulants?].
AB  - The risk of lumbar haematoma potentially increased by the association of regional
      anaesthesia and anticoagulant treatment has been widely debated. Few data are
      available in order to estimate the level of this risk, which is probably very
      low. However, even if it is now clear that regional anaesthesia is not potent
      enough to prevent postoperative deep vein thrombosis (DVT), a partial decrease in
      the DVT rate between 30 and 40% has been observed. Furthermore, no randomized
      double blind study has established the usefulness of the preoperative injection
      of heparin. Accordingly, when it is possible, it is best to avoid the
      preoperative injection and to start heparin treatment postoperatively. This
      solution is safe and effective.

PMID- 9183427
TI  - [Venous surgery of the lower limb: value of nerve blocks].
AB  - The author describes his experience of 152 cases of saphenous veins surgery
      performed under sciatic and femoral blocks. These nerves were located by a
      nervestimulation. Femoral nerve was blocked under the inguinal ligament; the
      sciatic nerve is blocked by the posterior approach, at the buttocks. 152
      patients, 136 cases were considered satisfactory: patients felt comfortable
      during and after the surgery; the stripper got up the vein more easily because of
      the vasoplegia; very good haemodynamic stability during changes in positioning;
      excellent nociceptive protection during the surgery. Sixteen cases were not
      satisfactory: the patient couldn't overcome his anxiety; the anaesthesiologist
      made technical mistakes; unbearable pain at the infero-internal face of the knee
      during the stripping. Considering these results, the blocks of the lower
      extremity could be an alternative to other anaesthetic techniques.

PMID- 9183428
TI  - [Combination of propofol-ketamine-vecuronium for total intravenous anesthesia
      under hazardous conditions].
AB  - A total intravenous technique using propofol, ketamine and vecuronium was
      successfully used on 29 patients treated for elective surgery at the UNPROFOR
      French Medical Group (Sarajevo, Bosnia Herzegovina). Operative conditions were
      satisfactory for the surgeons. Recovery was fast and emergence reactions very
      limited. No hypoxaemia was observed during the immediate postoperative period.
      The use of a propofol/ketamine/vecuronium combination is possible in field
      anaesthesia especially when opiates and inhalational agents are not available.

PMID- 9183429
TI  - [Evaluation of the cost of autologous erythrocyte concentrates in a hospital].
AB  - This study evaluated the cost of autologous and homologous blood products. The
      cost effectiveness of the transfusion therapy was not evaluated. To compare the
      different products, the cost of one gram of transfused haemoglobin was
      calculated. Acute normovolaemic haemodilution is the most economical technique.
      Intraoperative autologous transfusion without washing is the most expensive. All
      blood products from the autologous techniques, except the latter, were less
      expensive than homologous red cells.

PMID- 9183431
TI  - [Comparison of the efficacy of 2 antiseptic solutions in the prevention of
      infection from peridural catheters].
AB  - Two antiseptic solutions (iodine polyvidone and chlorhexidine) were compared-in a
      prospective non-randomized study including 294 parturient women. This study aimed
      to assess their efficacy against infections through epidural catheters. All
      catheters were subsequently cultivated. Cultures were significantly positive in
      3% of cases after iodine polyvidone and 1% after chlorhexidine decontamination
      (not significant). No clinical or biological infections were detected.
      Notwithstanding some apparently unavoidable but moderate contaminations,
      prevention of infections post epidural analgesia depends principally on a
      complete adherence to asepsia rules.

PMID- 9183432
TI  - [The Ombredanne equipment].

PMID- 9183430
TI  - [Caudal and spinal anesthesia in sub-umbilical surgery in children. Apropos of
      1875 cases].
AB  - Caudal and spinal anaesthesia are two techniques widely used in European
      children. The aim of this retrospective study was to evaluate the applicability
      of this practice in developing countries. The study concerned 1875 children, 1
      day to 17 years old. isobaric 0.5% bupivacaine was used for spinal anaesthesia (n
      = 730) and mixture a of 1% lidocaine-0.25% bupivacaine with epinephrine 1/200,000
      for caudal anaesthesia (n = 1,145). Spinal anaesthesia was performed in neonates
      and infants (< 3 years) and caudal anaesthesia in children (aged 14 days to 17
      years) undergoing urological and lower extremity surgery. No variation of heart
      rate, blood pressure or blood oxygen saturation (SpO2) were observed during
      surgery. Failure of the technique was less than 1%. These two regional
      anaesthesia techniques are easy to perform and are inexpensive. This is
      advantageous for developing countries.

PMID- 9183433
TI  - [New strategy for RNA vectorization in mammalian cells. Use of a peptide vector].
AB  - A major barrier for gene delivery is the low permeability of nucleic acids to
      cellular membranes. The development of antisenses and gene therapy has focused
      mainly on improving methods of oligonucleotide or gene delivery to the cell. In
      this report we described a new strategy for RNA cell delivery, based on a short
      single peptide. This peptide vector is derived from both the fusion domain of the
      gp41 protein of HIV and the nuclear localization sequence of the SV40 large T
      antigen. This peptide vector localizes rapidly to the cytoplasm then to the
      nucleus of human fibroblasts (HS-68) within a few minutes and exhibits a high
      affinity for a single-stranded mRNA encoding the p66 subunit of the HIV-1 reverse
      transcriptase (in a 100 nM range). The peptide/RNA complex formation involves
      mainly electrostatic interactions between the basic residues of the peptide and
      the charges on the phosphate group of the RNA. In the presence of the peptide
      vector fluorescently-labelled mRNA is delivered into the cytoplasm of mammalian
      cells (HS68 human fibroblasts) in less than 1 h with a relatively high efficiency
      (80%). This new concept based on a peptide-derived vector offers several
      advantages compared to other compounds commonly used in gene delivery. This
      vector is highly soluble and exhibits no cytotoxicity at the concentrations used
      for optimal gene delivery. This result clearly supports the fact that this
      peptide vector is a powerful tool and that it can be used widely, as much for
      laboratory research as for new applications and development in gene and/or
      antisense therapy.

PMID- 9183435
TI  - A second DNA polymerase activity in yeast mitochondria.
AB  - In eukaryotic cells, there is much evidence to indicate that the replication of
      the mitochondrial genome is carried out by a specific DNA polymerase named DNA
      polymerase gamma. In the yeast S. cerevisiae, a DNA polymerase gamma has been
      partially purified and the gene encoding the catalytic subunit identified. The
      characteristics of this enzyme are the same as those found in higher eukaryotes,
      except for the requirement for a higher magnesium concentration. During a
      purification procedure of yeast mitochondrial DNA polymerase, we have isolated a
      second DNA polymerase activity. Using different approaches ive have ruled out the
      possibility of nuclear contamination or a product of proteolysis. From its
      properties, this new DNA polymerase activity seems to be different from any yeast
      DNA polymerase. This new mitochondrial DNA polymerase activity provides evidence
      that the animal model of mitochondrial DNA replication cannot be generalized. The
      presence of two DNA polymerases in yeast mitochondria could reflect a different
      replication or repair mechanism.

PMID- 9183434
TI  - [Strong differences of mitochondrial DNA between Mediterranean sea and Eastern
      Atlantic populations of Sardinella aurita].
AB  - Digestion by restriction enzymes has been carried out on polymerase chain
      reaction products of the mitochondrial DNA control region of round sardine
      (Sardinella aurita) samples coming from the Eastern Atlantic and the
      Mediterranean Sea. The results show i) that, though the habitat is continuous,
      there is no gene flow between the two basins where two genetically differentiated
      groups can be recognized, ii) that each basin is genetically homogeneous and,
      iii) that the haplotypic diversity in the Mediterranean is between two and three
      times smaller than that observed in the Atlantic. These results can hardly be
      explained by a recent colonization from the Eastern Atlantic. This suggests that,
      for S. aurita and some other species, the Mediterranean Sea is genetically little
      influenced by the Eastern Atlantic.

PMID- 9183436
TI  - [Inotropic effect of isoprenaline and noradrenaline on chick embryo heart].
AB  - Isolated ventricles of developing chick embryo heart, paced at 1 Hz, were used to
      assess the positive inotropic responses to isoprenaline and noradrenaline in
      order to characterize the adrenergic receptors involved in these effects. In 7
      day-old-chick embryo heart ventricle, isoprenaline and noradrenaline exhibited
      similar potencies and efficacies. Moreover, propranolol (1 microM) inhibited the
      positive inotropic effect of isoprenaline and noradrenaline, while pentholamine
      (3 microM) failed to affect the latter response; in addition, phenylephrine (1
      microM-1 mM) had no positive inotropic effect. It was therefore concluded that
      isoprenaline and noradrenaline induce their effect via stimulation of beta
      adrenergic receptors. The efficacy of isoprenaline and noradrenaline and the
      potency of isoprenaline increased from the 7th to 10th day while the potency of
      noradrenaline decreased. The decrease in noradrenaline potency with age was
      attributed to its uptake, while the increase in isoprenaline potency was
      attributed to the increase in beta-adrenergic receptors. However, the increase in
      efficacy of both isoprenaline and noradrenaline with age might be due to the
      higher density and/or higher maturity of contractile proteins.

PMID- 9183437
TI  - Putative neurosurgical transmission of Creutzfeldt-Jakob disease with analysis of
      donor and recipient: agent strains.
AB  - A woman, aged 59 years, underwent a cortical biopsy that led to the diagnosis of
      Creutzfeldt-Jakob disease (CJD). A man, aged 46 years, underwent cranial surgery
      in the same department 3 days later for brain contusion, with an uneventful
      recovery. Twenty six months later, he developed clinical signs of CJD with a
      typical EEG pattern. Both cases exhibited features of the 'ataxic' form of the
      disease with depletion of cerebellar granule cells, without kuru plaques or PrP
      deposits. PrP deposits were immuno-histochemically observed in the cerebrum,
      spinal cord and peripheral nerve. Molecular genetic analysis performed on brain
      tissue revealed the codon 129 polymorphism to be Met129Met in the donor and
      Met129Val in the recipient. The shared 'cerebellar' phenotype and the genotypic
      discrepancy between the two patients lead us to postulate that the 'cerebellar'
      agent strain plays a major role in CJD phenotype and transmission.

PMID- 9183438
TI  - [The operon after 25 years].

PMID- 9183439
TI  - Human deoxycytidine kinase as a conditional mutator in Escherichia coli.
AB  - The chemical diversification of DNA precursors was undertaken in Escherichia coli
      by expressing the human gene for deoxycytidine kinase, and supplying such
      recombinant strains with nucleoside analogues bearing an altered base or sugar.
      Arabinocytidine and dideoxycytidine thus became highly toxic to E. coli in the
      sub-millimolar range. Deoxynucleosides bearing isoadenine (2-aminopurine) and
      isoguanine (2-hydroxy-6-aminopurine) showed a high mutagenic potency towards the
      recombinant strains, to an extent comparable to that of the most efficient
      mutator alleles (dnaQ). These findings open the way to the propagation of
      chemically remodelled nucleic acids and to the controlled hypermutagenesis of
      plasmids in vivo.

PMID- 9183440
TI  - Increased longevity and resistance to heat shock in Drosophila melanogaster flies
      exposed to hypergravity.
AB  - In recent years, attempts have been made to increase longevity in animal models
      (caloric restriction in rodents or overexpression of catalase and superoxide
      dismutase in transgenic flies, for instance). We report here that flies submitted
      to hypergravity (3 or 5 g), for 1 or 4 weeks starting from the second day of
      imaginal life and transferred after that time to 1 g, have a higher resistance to
      heat shock than flies living continuously at 1 g. Furthermore, male flies that
      had lived for 2 weeks from the second day of life at 3 or 5 g, lived longer than
      those living all the time at 1 g; no longevity increase was observed in females.
      As far as we know, this is the first example in flies showing that a mild stress
      at a young age not only increases resistance to an acute stress but also
      increases longevity. A hypothesis to explain these results could be that heat
      shock proteins, which are induced by various stress factors, are synthesized in
      conditions of hypergravity.

PMID- 9183441
TI  - Simultaneous functional expression of swelling and forskolin-activated chloride
      currents in primary cultures of rabbit distal convoluted tubule.
AB  - Ionic Cl- currents induced by cell swelling and forskolin were studied in primary
      cultures of rabbit distal convoluted tubule (DCTb) by the whole-cell patch clamp
      technique. We identified a Cl- conductance activated by cell swelling with an
      hyperosmotic pipette solution. The initial current exhibited an outwardly
      rectifying 1-V relationship, whereas steady state current showed strong decay at
      depolarized membrane potentials. The ion selectivity was I- > Br- > Cl- > >
      glutamate. The forskolin-activated Cl- conductance demonstrated a linear I-V
      relationship and its ion selectivity was Br- > Cl- > I- > glutamate. This last
      conductance could be related to the CFTR (cystic fibrosis transmembrane
      conductance regulator) previously identified in these cells. NPPB inhibited both
      Cl- currents, and DIDS inhibited only the swelling-activated Cl- current.
      Forskolin had no effect on the activation of the swelling-activated Cl- current.
      In DCTb cells which exhibited swelling-activated Cl- currents subsequently
      inhibited by DIDS, forskolin could activate CFTR related Cl- currents. In the
      continuous presence of I- which inhibited CFTR conductance, forskolin did not
      modify the swelling-activated current. The results suggest that both Cl-
      conductances could be co-expressed in the same DCTb cell and that CFTR did not
      modulate the swelling-activated conductance.

PMID- 9183442
TI  - [Vagal sensory reinnervation and composition of the sterno-cephalic muscle in
      rabbits].
AB  - The crossed nerve anastomosis between the peripheral end of the vagus nerve, cut
      above the nodose ganglion, and the peripheral end of the accessory nerve has
      demonstrated the capacity of some vagal afferents to reinnervate, via the
      accessory nerve stump, certain sternocephalicus muscle fibers in the rabbit.
      These results add to our understanding of the capacity of these afferents to
      counter the past-denervational atrophying process that occurs in the reinnervated
      muscles and to evaluate the changes induced in these muscles during
      reinnervation. Our work shows that within 3 months, the vagal sensory
      reinnervation of previously denervated sternocephalicus muscles induces their
      total weight recovery. This recovery is concomitant on the one hand with the
      hypertrophy of the four muscle fiber types (I, IIBD, IIC and IIA) identified
      histochemically in the normal muscles and, on the other, with the appearance of
      small newly formed myofibers, which are often underlined by characteristic
      central nuclei. The vagal sensory neurones induce important changes in the
      percentages and the muscle cross-sectional distribution of the fibers in
      reinnervated muscles. In these muscles we see also the disappearance of the fast
      myosin heavy chains MHCIIB and MHCIID, the upholding of the fast MHCIIA
      percentage and an increase in the slow MHCI isoform.

PMID- 9183443
TI  - Reconstruction of human maxillary defects with nacre powder: histological
      evidence for bone regeneration.
AB  - The defective areas in the premolar-molar region of maxillary alveolar bone of
      eight patients were reconstructed using powdered nacre from the giant oyster
      Pinctada maxima. Histological, microradiographic and polarized light studies of
      drill biopsies taken 6 months postoperatively showed that nacre was tightly bound
      to newly-formed bone. The nacre was gradually and centripetally biodissolved and
      replaced with immature and then mature lamellar bone. These results are in
      agreement with our previous experimental in vitro data indicating that nacre has
      good osteogenic properties.

PMID- 9183444
TI  - [Value of the protein profile in unexplained inflammatory syndromes].
AB  - The diagnosis of unexplained inflammatory syndromes requires many investigations
      which are commonly expensive, often invasive and must be repeated several times.
      A means for physicians to improve the diagnosis procedure would be to have new
      tests available to select the best diagnosis procedures. In order to test the
      value of the protein profile (PP) in the case of unexplained inflammatory
      syndromes, we prospectively studied 95 among 650 patients admitted in our unit
      for an inflammatory syndrome defined by a C Reactive Protein level > 2 mg/dL and
      a sedimentation rate > 30 mm, which remained unexplained after a 5 day
      hospitalization (49 men, 46 women; mean age: 62.9 +/- 12.3 years). PP has been
      considered as a useful test for the diagnosis in 21 cases (22%) having been
      definitively established by pathologic examination (42%), radiologic procedures
      (24%), endoscopy (19%), immunological tests (19%), and serological test (9.5%).
      The definitive diagnosis was a systemic disease in 12 cases, infection (four
      cases), malignancy (three cases), amyloidosis (one case) and occult intestinal
      bleeding (one case). CONCLUSION: Our data indicate that PP is a useful test for
      the diagnosis of unexplained inflammatory syndromes; its main utility is the
      disclosure of some specific biochemical syndromes available for better selecting
      the definitive diagnosis procedures.

PMID- 9183445
TI  - [Limitations of the protein profile for diagnostic orientation in initial
      internal medicine consultation. Prospective study on 76 patients].
AB  - Determination of the protein profile of orientation (PPO) is now considered by
      some authors as a means of improving the diagnosis in internal medicine. The
      feasibility of systematizing this practice was investigated in 76 outpatients (79
      included, three excluded secondarily) seen for pathology of undetermined
      diagnosis. The 79 patients (mean age: 52 years) underwent the classical
      biological explorations plus PPO. The physicians were divided into two groups
      (seniors and assistants). Two complete clinical files were established for each
      patient, with one difference concerning inflammatory and immunologic data: one
      file included the minimum number of tests considered necessary by the physician
      and the other the complete PPO (nine proteins). Each file (with or without PPO)
      was randomly distributed to one of two physicians in the same group. Each
      physician filled in a diagnostic evaluation sheet indicating whether there was
      organic pathology or not, the main diagnosis (inflammatory, neoplastic,
      infectious or other), the secondary diagnosis and the hypothesis of probability.
      The relevance of the clinical opinion was analyzed by an internal medicine
      specialist from outside the department with 40 years of clinical experience. The
      duration of symptoms before the medical visit was from 3 weeks to 5 years (mean 6
      months). A diagnosis of organic pathology was reached for three out of four
      patients. Sixty-seven patients were seen again after a minimum of 6 months, and
      nine were lost to follow-up. Diagnostic efficiency was no greater for cases with
      PPO, which appears to be a biological examination of second intention. We suggest
      that the term "protein profile of orientation" be replaced by "broad protein
      profile."

PMID- 9183446
TI  - [Serotonin syndrome: critical review of the literature].
AB  - Since Sternbach's first review, serotonin syndrome has been reported many times.
      Our purpose was to examine this concept's pertinence, utility and meaning. Its
      physiopathology remains unclear: 5-HT1A receptors activation is certain, but
      others mechanisms and individual or family factors could be also involved.
      Appearance circumstances are more various than first expected. The concept of
      serotonin syndrome seems to bring together entities that differ in
      physiopathology and seriousness, and we propose to distinguish between serotonin
      syndrome and other types of syndromes. Knowing serotonin syndrome is useful both
      for prevention and for recognizing it as a potentially lethal emergency.

PMID- 9183447
TI  - [Edema caused by retroperitoneal and tricuspid fibrosis with sclerodermatous
      cutaneous involvement disclosing carcinoid tumor. Apropos of a case and review of
      the literature].
AB  - A 65-year-old female was admitted with leg edema by retroperitoneal fibrosis and
      tricuspid valve incompetence by fibrosis, cutaneous fibrosis, moderate flushing
      over the upper body without diarrhea. It revealed an ileal carcinoid tumor with
      hepatic metastases. Octreotide (Sandostatine), tumor excision and interferon
      alpha 2b treatment led to a regression of flushing and edema, a reduction of
      fibrosis and a stabilization of the metastatic carcinoid, with normal serotonin
      levels.

PMID- 9183448
TI  - [Lipomatosis induced by corticosteroid therapy].
AB  - Steroid-induced lipomatosis usually presents as a localized hypertrophy of the
      adipose tissue and seems more common than previously thought. Most patients
      develop this phenomenon after prolonged administration of moderate to high doses
      of oral corticosteroids. The localizations are numerous and determine the
      clinical presentation. Often asymptomatic, they can also be revealed by worrying
      symptoms usually due to a compressive syndrome. The most frequently reported
      localizations (spinal epidural, retro-orbital, mediastinal) are also the most
      clinically apparent. The cessation or reduction of steroid therapy, when
      medically possible, inconsistently results in the decrease or disappearance of
      the lipomatosis deposits. Computerized tomography or magnetic resonance imaging
      are the most helpful diagnostic means. Interestingly, these lipomatoses have
      rarely been reported in patients with Cushing disease. Their pathophysiology
      remains poorly elucidated and may imply an inhibition of the brown adipose tissue
      lipolysis.

PMID- 9183449
TI  - [Carcinomatous meningitis: rare complication of bladder cancer].
AB  - The sites of metastases of transitional cell carcinoma of the bladder are nodes,
      liver, lung and bone, but the meningeal infiltration is rare. Therefore, one case
      of meningeal carcinomatosis is reported. After cystectomy for an undifferentiated
      carcinoma of the bladder, the patient received adjuvant chemotherapy. Three
      months after treatment completion, symptoms of cerebellar ataxia occurred and
      gradually confusion appeared. The initial cerebra spinal fluid showed clumps of
      malignant cells. The patient died 15 days after the neurological symptoms
      occurred. The clinical diagnosis of meningeal carcinomatosis is based on
      neurological manifestations at more than one level of the neuraxis. Symptoms may
      present simply as headache or confusion. Meningeal carcinomatosis from urothelial
      cancer seems to show some specific features: poorly differentiated tumour and
      high frequency of cerebellar symptoms. Intrathecal treatment essentially has a
      pain-effect. Mean survival time is as short as 20 weeks. The increasing incidence
      of this neurological complication in urothelial cancer does not only result from
      an increase in patient longevity but also from possible side-effects of
      chemotherapy, so as localized changes in blood-brain barrier permeability induced
      by antineoplastic drugs. Therefore, we may wonder whether meningeal
      carcinomatosis might not be regarded as an iatrogenic effect.

PMID- 9183450
TI  - [Surgical pulmonary biopsies in patients with HIV infection: results apropos of a
      series of 21 cases].
AB  - This retrospective study reports the results of surgical lung biopsies in 21
      patients infected by HIV. Diagnostic was assessed by surgical lung biopsies in
      66% of cases with a 5% immediate post-operative mortality and a 80% survival rate
      after one month. Therapeutic management was modified in 38% of cases. These
      results are in concordance with previously published literature and emphasize
      that such a procedure should only be performed after other diagnostic procedures,
      including at least a bronchial endoscopy associated to a BAL and/or
      transbronchial biopsies.

PMID- 9183451
TI  - [Severe hemorrhagic complications during treatment with low molecular weight
      heparin. Apropos of 2 cases].
AB  - Two cases of fatal bleeding in patients treated with low molecular weight heparin
      for deep vein thrombosis are reported. Risk factors for bleeding were: severe
      underlying disease (cancer in one case, morbid obesity and cardiac failure in the
      other), age over 80 years and worsening of renal insufficiency in both cases,
      recent surgical procedure in one case. Anti-Xa activity was beyond the
      therapeutic range at the time of bleeding in both cases. The usefulness of
      biologically monitoring the treatment of deep vein thrombosis with low molecular
      weight heparin is discussed.

PMID- 9183452
TI  - [Vanishing aneurysm].

PMID- 9183453
TI  - [Immune and non-immune intestinal villous atrophies].

PMID- 9183454
TI  - [Physiology of erection].
AB  - The peripheral pharmacology of local mechanisms of penile erection is known today
      thanks to recent advance in the study of the regulation of erectile tissue smooth
      muscle tone. Smooth muscle fibers present in the corpus cavernosum and arteries
      destined to the penis relax in response to the release of non adrenergic non
      cholinergic neuromediators synthetized by postganglionic parasympathetic nerve
      fibers present in the cavernous nerves. Nitric oxide is the main proerectile
      neuromediator. Noradrenaline, released by sympathetic fibers, contracts penile
      smooth muscle fibers and is antierectile. Recent progress in the peripheral
      pharmacology of penile erection allows new perspectives in the treatment of
      erectile dysfunction. The spinal cord represents a major site for the neural
      regulation of penile erection. The latter occurs in response to stimuli from
      peripheral or supraspinal origin. Different neural structures in the brainstem
      (nucleus paragigantocellularis), pons and hypothalamus (nucleus
      paraventricularis) send projections to the thoracolumbar sympathetic and
      lumbosacral parasympathetic nuclei at the origin of proerectile peripheral
      pathways. Serotonin and oxytocin are candidates as neuromediators involved in the
      supraspinal control of penile erection. Studying the central command of penile
      erection allows an approach to the pathophysiology of psychogenic erectile
      dysfunction.

PMID- 9183455
TI  - [Nosology, epidemiology, clinical quantification of erectile dysfunctions].
AB  - After a review of the literature and of our own data base this article specifies:
      the nosology of erectile dysfunction (ED) defined as an inability to achieve
      enough rigidity for a satisfactory intercourse. This lack of firmness is
      frequently associated with a loss of libido (37%), performance anxiety (37%), and
      premature ejaculation (40%). The prevalence of ED in the overall French
      population, age 18 to 70 years is 39% (11% presenting permanent ED defined as a
      rate of failure to perform of 50%). This rate increases with age to 52 and 25%
      respectively. A quantification of the symptomatology is proposed scoring three
      different aspects of sexual activity during intercourse, erectile activity in
      absence of intercourse, patient's satisfaction, and partner satisfaction. Figures
      of normal subjects and patients with ED are presented.

PMID- 9183457
TI  - [Vascular and functional evaluation of erectile dysfunctions using erection
      provocation tests].
AB  - The provoked erection test (TEP) consists in exploring successively, the sexual
      arteries, the penile volume and rigidity charges after pharmacological and sexual
      visual stimulation. Quantified arteria were proposed to evaluate the arterial
      flow and the caverno venous component obtained though a global appraisal of the
      erectile function. From these, TEP allows a quick approach to the diagnosis of
      erectile dysfunction for an early therapeutic decision.

PMID- 9183456
TI  - [Hormones and male sexuality].
AB  - In the review of the physiological, pathological and therapeutical aspects of the
      role of hormones in the erectile process four main topics are discussed:
      gonadotrop axis dysfunction, hyperprolactinemia, impotence and the potential
      climacteric male deficit. The conclusion for therapy is that only organic
      lowering of testosterone should be treated with a dosage adapted to the level of
      the decrease.

PMID- 9183458
TI  - [The psychiatrist and the impotent patient].
AB  - Psychiatrists may face impotence in two circumstances: the patient complains of
      his impotence, or suffers from depression or another psychiatric condition. It is
      in the way in which the patient and the symptom are approached by the
      psychiatrist that a confident and beneficial relation may be established.

PMID- 9183460
TI  - [Intracavernous injections and new medical treatments of impotence].
AB  - Intracavernous injections (IIC) of vasoactives drugs is the most frequent
      treatment of erectile dysfunction (ED). Indications, technique and immediate as
      well as long term results are presented here. A retrospective quantified study of
      the follow up at 5 years of use shows that 94% of the patients who still use the
      treatment are satisfied, comparing with 48% who have stopped, and 21% who have
      never taken it. The overall rate of patients cured (i.e.; having a normal sexual
      life, without using the treatment) is 26.6%. The drop out rate linked to the
      treatment itself is 25%. Complications are seldom and benign: 7% of prolonged
      erection episodes, all solved by a medical regimen, mostly administered by the
      patient itself; nodules are present in 3% of the patients or do not interfere
      with the efficacy of the treatment; they are 1.6% Peyronie's like plaques.
      Perspectives opened by new treatments such as the Muse system and oral therapy by
      sildenafil or apomorphine are discussed.

PMID- 9183459
TI  - [Clinical models and decisional algorithm in the management of erectile
      disorders].
AB  - The diagnosis of erectile dysfunction (ED) needs an appropriate evaluation of
      global function and specific component of the erection. We have used a quantified
      methodology to grade each of the specific factors: arterial, venous, neurologic,
      endocrine, psychological and anxiety, in four groups of increasing severity. With
      this information each patient is them classified organic, psychological or mixed.
      The prevalence of "mixed" aetiology appears in the statistical objective offered
      by two different retrospective studies with a 76% rate of psychological
      prevalence and a 85% of organic prevalence. In two out of three of the patients
      both factors are present.

PMID- 9183461
TI  - [Surgical treatments of erectile impotence].
AB  - Impotence affects 10 to 15% of the male population. Organic factors are
      recognized in 80% of cases. Intracavernosal injections of vasoactive agents
      (Virag) have provided advances in the physiopathologic understanding of impotence
      and provide new ways of treating this incapacity. However this option is
      inaffective in most organic cases: arteriogenic, venogenic or disorders of smooth
      cavernous muscle. Vasoactive injections for many reasons are abandoned in about
      40% of the cases. Two kinds of surgical management can be performed:
      microrevascularization in order to restore the arterial penile flow or to reduce
      penile venous flow during erection; implantation of penile prosthesis when other
      therapeutic possibilities are exhausted. Arterialization of the deep dorsal vein
      (DDV) appears to be the best procedure in arteriogenic and principally venous
      impotence. Erectile function in theses case is restored in 60% of our patients.
      Two types of prostheses can be implanted: semi-rigid with an axial permanent
      rigidity and inflatable or hydraulic devices with a flaccid aspect after
      intercourse. These prostheses are technically successful in 75 to 90% of cases,
      but partner satisfaction does not match surgical success rates.

PMID- 9183462
TI  - [La Peyronie disease. Historical, epidemiological, physiopathological data.
      Diagnostic and therapeutic approaches].
AB  - The origin of Peyronie's disease remains obscure although the first description
      dates back to 1743. The prevalence of the disease is 388.6 per 100,000
      population. Little physiopathologic data is available. Repeated microtrauma to
      the tunica albuginea appears to favor the onset of inflammatory phenomena, in
      turn the source of fibrosis. Clinical examination remains the ideal method for
      diagnosis and follow-up: it can be completed by ultrasonography of the corpora
      cavernosa. Magnetic resonance imaging does not appear to provide any significant
      benefits. The inflammation and pain encountered in early stages of the disease
      can be managed medically. Numerous treatments have been tested (oral route or
      local injections); results are in the course of evaluation. In the absence of
      well-controlled clinical trials, there is no standard medical therapy.
      Radiotherapy today appears inadvisable. The sequels of Peyronie's disease can be
      treated surgically, especially in patients who can maintain and adequate erection
      but suffer from a deformation incompatible with sexual activity. Numerous
      technical artifices have been proposed; correction of deformations is generally
      satisfactory but perfections need to be made concerning the quality of erection.
      Patients with advanced disease and severe erectile insufficiency can be offered
      reconstructive surgery using penile implants: results of the various procedures
      are analyzed.

PMID- 9183463
TI  - [Prevention and treatment of erectile disorders in sickle cell disease].
AB  - Priapism is a frequent and serious cause of morbidity in males with sickle cell
      disease. Acute priapism (AP) is preceeded in two-thirds of the cases by repeated
      minor events called stuttering priapism (SP). Since 1994, we have used a specific
      approach to prevent the commonly devastating effects of AP, using the alpha
      adrenergic agent etilefrine. Treatment of AP has been simplified (drainage
      without aspiration followed by one or two intracavernous injections (ICI) of 10
      mg of etilefrine, until detumescence). For SP lasting more than one hour or
      causing pain, we use oral etilefrine and/or self ICI. This strategy was effective
      in five patients seen having AP, 21 patients with SP; it is simple, cheap, and
      avoids surgical procedure and transfusion. Moreover, erectile dysfunction,
      present in three patients, has been treated safely by ICI of protaglandins.

PMID- 9183464
TI  - Exposure and risk factors among elderly drivers: a case-control study.
AB  - To study the risk factors associated with exposure, aging, and other
      characteristics of elderly drivers, a case-control survey of 557 licensed drivers
      was conducted among residents of medium-sized, small towns and rural areas in
      Quebec, Canada. The subjects, aged 68 and over, were selected from the database
      of the provincial Automobile Insurance Board. The case group was chosen on the
      basis of performance, either accidents or violations, during the preceding three
      years. Cases were matched to a control group (blank file for the last three
      years) on a stratification basis (age, gender, region) in the proportion of two
      controls for one case. The survey which was conducted through a mail
      questionnaire achieved a participation rate of nearly 60%. The logistic
      regression method was used to assess the risk (odds ratios). The results of this
      study reveal that risk is proportional to the frequency of daily vehicle use or
      annual kilometrage. The hypothesis that elderly drivers who rarely expose
      themselves are at more risk is thus rejected. Vulnerable subgroups were the most
      elderly (> 77), city or suburban residents, the unmarried, and white collars
      (during active life).

PMID- 9183465
TI  - What surviving drivers learn from a fatal road accident.
AB  - The effects of involvement in a fatal accident on surviving drivers' subsequent
      driving behavior were studied. The quantity (mileage) and quality of driving
      (offences in driver records) of 245 surviving drivers were compared in three-year
      periods before and after the accident. A random sample of 253 drivers from the
      driver register were additionally used as controls. The data showed that about
      half of the car drivers decreased their driving, with greater reductions being
      associated with more serious injuries. However, the total number of convictions
      did not reduce but even showed a tendency to increase in proportion to the amount
      of driving. The proportion of car drivers with post-crash offences was
      approximately constant (27-32%) independent of any change in mileage. The data
      suggest that professional heavy-vehicle drivers incurred fewer convictions during
      the post-crash period in comparison to car drivers. Thirty-seven surviving
      drivers were further interviewed on the duration and specificity of the effects.
      With the exception of three drivers, all said that the fatal accident had
      affected their driving behavior, but only for a relatively short time. Most
      commonly, the drivers reported that the effect was limited to those circumstances
      and situations which led to the accident and did not generalize to safer driving
      practices. This study suggests that car drivers, if not seriously injured,
      typically return to their 'normal' driving within a few months, while heavy
      vehicle drivers show a tendency towards more cautious behavior after a fatal
      crash in terms of violations, presumably due to the continuous reinforcement
      which the latter receive in their work community.

PMID- 9183466
TI  - Methodological issues in testing the hypothesis of risk compensation.
AB  - The hypothesis of risk compensation implies that persons experiencing a real or
      perceived change in the riskiness of an activity will alter their consumption of
      that activity to obtain a preferred combination of risk and reward. In evaluating
      whether individuals display compensating behavior in response to safety
      interventions, not all persons subject to the intervention will necessarily
      display compensating behavior, even if the hypothesis is correct: the hypothesis
      has testable implications only for the subset of persons subject to the
      intervention who perceive that their risk has changed. This paper argues that
      methodologies that include persons for whom the hypothesis has no testable
      implications (against a null hypothesis of no compensation effect) result in
      estimates of the compensation effect and test statistics which are biased towards
      zero. Previously published data on motor-vehicle-related injuries to cyclists and
      pedestrians in Britain before and after a mandatory safety-belt-use law went into
      effect were used to infer the size of this bias. In these data, the inclusion of
      persons for whom the hypothesis of risk compensation has no testable implications
      appears to have resulted in estimates of a risk-compensation effect which are too
      small by about half. This work suggests that the British data are consistent with
      a risk-compensation effect of 7-13 percent, and raises important methodological
      issues in testing the hypothesis of risk compensation.

PMID- 9183467
TI  - An investigation of behavioural adaptation to airbags and antilock brakes among
      taxi drivers.
AB  - Previous research has indicated that safety measures may lead to behavioural
      adaptation (also termed risk compensation) among road users, partly or completely
      offsetting the intended safety effects. There is, however, limited knowledge
      about characteristics of safety measures possibly determining the occurrence of
      behavioural adaptation. The present study addresses the relationship of driving
      behaviour to two different kinds of in-car safety equipment, airbags and antilock
      braking systems (ABS). It is hypothesized that accident-reducing measures like
      ABS are compensated for to a larger extent than injury-reducing measures like an
      airbag. On-road unobtrusive measurements of speed, headway, lane occupancy, lane
      changes, and variability of lateral position were performed on 213 taxis, on the
      basis of video recordings of traffic travelling to Oslo airport. The behavioural
      data were matched to questionnaire information collected when the taxis arrived
      at the airport. In addition to information regarding ABS and airbags, the drivers
      reported personal background information and answered questions about driving
      behaviour. Taxis with ABS had significantly shorter time headways than taxis
      without ABS. There were no relationships with speed, possibly because dense
      traffic during the observation period may have prevented the drivers from driving
      at their preferred speed. Simple comparisons also showed fewer lane changes and a
      lower rate of seat-belt use among drivers of taxis with ABS. However, multiple
      regression analyses indicated that the latter effects might be explained by
      driver background factors or by car characteristics other than ABS or airbag. The
      headway results support the hypothesis of larger compensation for accident
      reducing than for injury-reducing measures.

PMID- 9183468
TI  - Fatal pedestrian accidents in France: a typological analysis.
AB  - This study examines reports on fatal pedestrian accidents which occurred in
      France between March 1990 and February 1991. 1289 pedestrians were killed in
      these accidents. The main characteristics of pedestrians were analyzed: age and
      sex, movements, change of transport mode and alcohol impairment. In order to
      describe the relationships between the different criteria, a typology of
      pedestrian accidents is proposed. It is based on a correspondence analysis,
      followed by a classification. This classification clearly identifies four groups:
      elderly pedestrians who were crossing a road in an urban area; children involved
      in daytime accidents in urban areas whilst playing or running; intoxicated
      pedestrians involved in night-time accidents in the country whilst walking on the
      carriageway: pedestrians involved in secondary accidents and changes of transport
      mode. It is recommended to adapt information campaigns or education programs to
      the pedestrian group they address.

PMID- 9183469
TI  - Motor-vehicle crash-injury risk factors among American Indians.
AB  - The rates of motor-vehicle crash mortality are highest among American Indians and
      Alaska Natives, compared to other ethnic groups. The aim of this study was to
      compare risk factors for motor-vehicle crashes and occupant injuries between
      rural and urban American-Indian (AI) drivers, and between rural AI and non-AI
      rural drivers. A statewide traffic-accident database was linked to the Indian
      Health Service patient-registration database to identify crashes that involved
      American-Indian drivers. Using a cross-sectional design, crashes occurring in a
      two-county region during 1989 and 1990 were studied. A total of 9329 motor
      vehicle crashes involving 16,234 drivers and 6431 passengers were studied. Two
      percent of drivers were American Indian. Compared to American-Indian drivers in
      urban crashes, rural crashes involving American-Indian drivers were more likely
      to result in injury or death (38% vs 64% p < 0.001). The difference in risk for
      crashes between urban and rural non-AI drivers was not as high (42% vs 33%). Only
      44 percent of rural American-Indian motor-vehicle occupants reported wearing seat
      belts, compared to 70 percent of urban American-Indian occupants (p < 0.05).
      Rates of driver alcohol impairment, as assessed by the police, were much higher
      among AI drivers and highest among rural AI drivers. We conclude that, compared
      to non-American-Indian drivers, AI drivers are less likely to be restrained and
      more likely to be alcohol-impaired at the time of the crash. These risks are
      higher among rural AI drivers than urban AI drivers.

PMID- 9183470
TI  - Can a combination of local, regional and national information substantially
      increase bicycle-helmet wearing and reduce injuries? Experiences from Sweden.
AB  - Is it possible to substantially reduce the incidence of injuries related to
      cycling through the provision of information on helmet wearing? This issue has
      been investigated in Skaraborg County, Sweden, where 90 percent of all pre-school
      children now use bicycle helmets. For children under 15, there was an average
      annual decrease in all bicycle-related injuries of 3.1 percent, equivalent to a
      decrease of 48 percent over the study period, 1978-93 (for head injuries, 59%).
      Sweden as a whole showed a reduction of 32 percent in bicycle-related injuries
      (head injuries, 43%). In Skaraborg, children have been the target of helmet
      wearing programs at local and regional levels since 1982, and at national level
      since 1987. The elderly have not been targeted in helmet-wearing programs;
      currently, they scarcely wear helmets at all, and showed a significant increase
      in their injury rate over the period (4.7% annually). The number of concussions
      sustained by helmet-wearers is estimated to be one-third fewer than that of non
      wearers. Comparisons with Australia and some parts of the U.S.A. indicate that,
      despite the significant decrease in Skaraborg, greater effects might be
      achievable if information is supplemented by compulsory-helmet-wearing
      legislation.

PMID- 9183471
TI  - Costs of gunshot and cut/stab wounds in the United States, with some Canadian
      comparisons.
AB  - This article estimates the costs of U.S. gunshot and cut/stab wound by intent. It
      also compares U.S. to Canadian gunshot experience. Incidence data are from
      published sources, the National Hospital Ambulatory Medical Care Survey (NHAMCS),
      and cause-coded emergency department discharge and hospital discharge data
      systems. Medical care payments and lost earnings per case come from National
      Crime Survey data, a literature review, and weighting of costs by diagnosis from
      Databook on Nonfatal Injury-Incidence. Costs, and Consequences by Miller et al.
      (The Urban Institute Press, Washington, DC. 1995) with the diagnosis distribution
      of penetrating injuries from the discharge data systems. Quality of life losses
      are estimated primarily from jury awards to penetrating injury victims. In 1992,
      gunshots killed 37,776 Americans; cut/stab wounds killed 4095. Another 134,000
      gunshot survivors and 3,100,000 cut/stab wound survivors received medical
      treatment. Annually, gunshot wounds cost an estimated U.S. $126 billion. Cut/stab
      wounds cost another U.S. $51 billion. The gunshot and cut/stab totals include
      U.S. $40 billion and U.S. $13 billion respectively in medical, public services,
      and work-loss costs. Across medically treated cases, costs average U.S. $154,000
      per gunshot survivor and U.S. $12,000 per cut/stab survivor. Gunshot wounds are
      more than three times as common in the U.S. than in Canada, which has strict
      handgun control. With the same quality of life loss per victim, gunshot costs per
      capita are an estimated U.S. $495 in the U.S. vs U.S. $180 in Canada. Per gun,
      however, the costs are higher in Canada, Gunshot wound rates rise linearly with
      gun ownership.

PMID- 9183472
TI  - United States passenger-vehicle crashes by crash geometry: direct costs and other
      losses.
AB  - The personal and societal losses caused by motor-vehicle crashes are significant.
      This paper provides tools that describe these losses for 30 different crash
      geometries. Persons involved with the development and implementation of crash
      countermeasures can use these tools to prioritize their countermeasure approach.
      Multiple vehicle crashes currently account for much larger direct costs but only
      slightly more years lost than single vehicle crashes. Direct expenditures on
      multiple vehicle crashes exceed $41 billion per year; they claim 974,000 years of
      life and functioning. Direct expenditures on single vehicle crashes exceed $18
      billion per year; they claim 937,000 years of life and functioning.

PMID- 9183473
TI  - The effects of paved shoulders on accidents on rural highways.
AB  - This paper presents the results of a project that sought to determine the safety
      effect of paving shoulders in rural roads Victoria, Australia. Data were obtained
      on the location, condition and cost of recent shoulder-paving projects on two
      lane two-way roads (i.e. one lane in each direction). Accident data were obtained
      for these sites, and a before-and-after comparison, using control sites, was
      undertaken. Most shoulder-paving programs examined involved a low-cost paving of
      an existing shoulder, typically involving an interim bituminous sealing
      treatment, followed a year or so later with a reseal in conjunction with a
      pavement reseal. The shoulder width is typically between 600 and 1200 mm, with
      600 or 800 mm being the most common. The results for this type of treatment
      indicate that shoulder paving was associated with a statistically-significant
      reduction in casualty accident frequencies at sites where it was installed on two
      lane two-way rural highways in Victoria. Overall, casualty accidents were reduced
      by 41 per cent on a per vehicle kilometre basis at such sites, which is
      equivalent to a reduction of 0.071 casualty accidents per million vehicle
      kilometres. The break-even point (the point at which it is economically
      worthwhile to pave shoulders) is at a traffic flow of about 360 vehicles per day.
      The main accident reductions are for accidents involving rear end, overtaking-
      out of control, off carriageway to left, and off carriageway to right into fixed
      object. A relationship between measures of economic worth (net present value and
      benefit/cost ratio) and traffic flow is developed.

PMID- 9183474
TI  - An epidemiological study of bicycle-related injuries.
AB  - The objectives of this study were to describe bicycle-related injuries in
      relation to injury patterns, age, gender and medical treatment in a defined
      Swedish population and to identify factors contributing to injury. The study
      group comprised all patients living in the county of Vastmanland, Sweden,
      visiting a physician or dentist because of bicycle-related injury during one year
      (November 1989-October 1990). Cyclists were mostly injured on pavements,
      pedestrian malls and cycle tracks. Twenty percent of the events occurred on
      public roads in urban areas; most frequently, the injured were in the age range 0
      24. The most common bicycle injury event involved no other party. The events were
      often caused by environmental factors, in combination with behaviour such as
      excessive speed, lack of attention, breach of traffic regulations or a co
      ordination problem. Head injuries, including oral injuries, were the most common,
      in particular among children and adolescents. One in four children in the age
      range 0-9 sustained an oral injury.

PMID- 9183475
TI  - Increased police enforcement: effects on speed.
AB  - Results of a field experiment in which a 35-km long stretch of road was subjected
      to an increase in police enforcement--mostly as stationary speed controls--are
      presented. A group of police officers was invited to plan and perform the
      enforcement based on their own experience and ideas. The level of enforcement
      reached a daily average of nine hours throughout an enforcement period of six
      weeks. Speed measurements were done in 60 and 80 km/h speed-limit zones before,
      during and after enforcement withdrawal, and were compared to another stretch of
      road. Average speeds were reduced by 0.9-4.8 km/h in both speed-limit zones and
      for all times of day. For some time intervals, the average speed and the
      percentage of speeding drivers were reduced for several weeks of the after
      period, demonstrating a time-halo effect of eight weeks at most. The percentage
      of speeding drivers was reduced in both speed-limit zones for all hours of the
      day except the morning rush hours 6.00-9.00 A.M. It is suggested that commuting
      drivers in the morning rush hours are most resistant to speed reduction. These
      results were statistically significant at alpha = 0.01.

PMID- 9183477
TI  - Two-vehicle side impact crashes: the relationship of vehicle and crash
      characteristics to injury severity.
AB  - Injury type and severity among front outboard occupants of passenger vehicles
      struck in the side by another passenger vehicle and recorded in the United States
      National Accident Sampling System Crashworthiness Data System were examined in
      relation to the location of impact, the angle of impact, occupant gender and age,
      seat belt use, the weight and body style of the side-impacted vehicle, and the
      weight and body style of the striking vehicle. Elderly occupants were three times
      as likely as younger occupants in similar crashes to be seriously injured.
      Serious injuries were also more likely for occupants seated on the struck side
      and occupants of lightweight passenger vehicles. After accounting for vehicle
      weight differences, struck-side occupants of cars were still much more likely to
      be seriously injured than struck-side occupants of light trucks. However, among
      occupants seated on the side of the vehicle opposite the impact, the likelihood
      of serious injury was higher for those seated in light trucks.

PMID- 9183476
TI  - The effect of time headway feedback on following behaviour.
AB  - A field study was conducted to assess the impact of continuous time headway
      feedback on following behaviour. An equipped vehicle was fitted with a microwave
      radar connected to a head-down display. The display was supplemented by an
      auditory tone which sounded if headway decreased below 1 second. Sixteen subjects
      participated in five consecutive sessions conducted on a U.K. motorway. The
      presence of the system and the time of the journey (i.e. rush hour vs off-peak)
      was manipulated across the experimental sessions. Results revealed that the
      presence of the system reduced the proportion of time the subjects spent at low
      headways (e.g. < 1 second). This effect was accentuated for: (a) subjects who
      habitually follow at shorter headways and (b) those scenarios characterised as
      following a lead vehicle at a constant velocity. The presence of the system
      increased time headway to a lead vehicle when an overtaking manoeuvre was
      initiated, but only in off-peak traffic. The system had no significant effect on
      speed-keeping behaviour or driver's mental workload.

PMID- 9183478
TI  - 150th anniversary of the creation of the first Chair of Paediatrics in the world.
      FT Berg appointed as Professor at Karolinska Institute in 1846.

PMID- 9183479
TI  - Evaluation of full-term infants fed an evaporated milk formula.
AB  - The objective of this prospective, cohort study was to compare the nutritional
      status of full-term infants who were fed human milk (BF, n = 29), formula (FF, n
      = 30) or evaporated milk formulae (EM, n = 30) for at least 3 months. Infants
      were seen at enrollment, 3 and 6 months, at which times a blood sample, diet
      record and anthropometric data were collected. Infants in the EM group received
      solids earlier (12 +/- 5 weeks) than did FF infants (15 +/- 4 weeks), and both
      were earlier than BF infants (19 +/- 4 weeks). Only 26% of the EM fed group
      received iron supplements as ferrous sulphate drops. Seven BF, 12 FF and 20 EM
      had abnormal ferritin values (< 10 ng ml-1) at 6 months. Copper intake was lower
      in the EM infants at 3 and 6 months. However, plasma copper and erythrocyte
      copper zinc superoxide dismutase (ZnCuSOD) levels did not differ between groups.
      Selenium intake was lower in the EM group (5 +/- 1 and 10 +/- 5 micrograms d-1; 3
      and 6 months) than in the FF infants (13 +/- 4 and 19 +/- 7 micrograms d-1; 3 and
      6 months). Erythrocyte SeGHSPx levels in EM infants were lower at 6 months (EM,
      33.2 +/- 3.4; FF. 35.2 +/- 3.9: BF, 36.1 +/- 3.8 mU mg Hb-1). Thiamin intake
      (0.99 +/- 0.08 and 1.24 +/- 0.32; 3 and 6 months, mg 1000 kcal-1) was higher in
      the FF group than in EM infants (0.38 +/- 0.39 and 0.66 +/- 0.38; 3 and 6
      months). There were more (13%) abnormal thiamin assays in the EM group at 6
      months than in the BF and FF infants (0%). In conclusion, infants fed evaporated
      milk formula receive adequate copper but may not receive enough thiamin or
      selenium. Unless supplemented from birth with medicinal iron, intakes of iron
      will be inadequate.

PMID- 9183480
TI  - Peak expiratory flow in healthy Turkish children.
AB  - This study was conducted on 1359 healthy, non-smoking Turkish children (727M,
      632F) with a mean age of 11.7 +/- 3.4 (6-17) years, in order to determine the
      normal values of peak expiratory flow (PEF) in Turkish children and to compare
      various peak-flow meters (PEFMs). PEF values increased with age and height in
      boys and girls. The relative increase in boys was significantly higher at puberty
      (p < 0.01). The values of Turkish children were found to be similar to those of
      Europeans. The results obtained from the three PEFMs were closely correlated.

PMID- 9183481
TI  - Effect of training on the aerobic power and anaerobic performance of prepubertal
      girls.
AB  - The purpose of this study was to investigate the effects of two, three times a
      week, 8-week training programmes on the aerobic power and anaerobic performance
      of 30 prepubescent girls, with a mean age of 9.6 y. Peak oxygen uptake assessed
      by an incremental discontinuous treadmill test, and peak power in 5 s and mean
      power over 30 s estimated from a Wingate anaerobic test were used as the
      criterion measures. Twelve girls trained using a continuous cycle ergometer
      programme, 11 girls followed a sprint running programme and the control group
      consisted of 7 girls. Both training groups significantly (p < 0.05) increased
      their peak oxygen uptake and peak power in 5 s. However, the increase reported
      here are lower than those generally observed in adolescents following training.
      The control group demonstrated no significant (p > 0.05) change in either
      variable. No significant (p > 0.05) changes in mean power over 30 s were observed
      in any group.

PMID- 9183482
TI  - A trial in the Karelian Republic of oral rehydration and Lactobacillus GG for
      treatment of acute diarrhoea.
AB  - In a controlled trial in Petrozavodsk, Karelia, the effects of oral rehydration
      and Lactobacillus strain GG (LGG) on recovery from acute diarrhoea (27%
      rotavirus, 21% bacterial aetiology) were studied in 123 children aged between 1
      and 36 months of age. On admission to hospital, the patients were first
      randomized to receive either isotonic oral rehydration solution (ORS) with
      osmolarity 311 mosmol/l and sodium 90 mmol/l (WHO-ORS), or a hypotonic ORS with
      osmolarity 224 mosmol/l and sodium 60 mmol/l (Light-ORS), and thereafter
      randomized to receive either 5 x 10(9) colony forming units of LGG or a matching
      placebo. The two ORS performed equally for acute rehydration, and oral
      rehydration with either ORS was associated with a shorter duration of diarrhoea
      than intravenous rehydration (p = 0.036). Patients receiving LGG had a
      significantly shorter duration of watery diarrhoea [mean (SD) 2.7 (2.2) days]
      than those receiving the placebo [3.7 (2.8) days, p = 0.03]. LGG significantly
      shortened the duration of rotavirus diarrhoea but not diarrhoea with confirmed
      bacterial aetiology.

PMID- 9183483
TI  - Clinical use of acid steatocrit.
AB  - Malabsorption of fat is an important gastrointestinal cause of malnutrition and
      growth retardation in childhood. The gold standard for the evaluation of fat
      malabsorption is the faecal fat balance method. The acid steatocrit method has
      recently been introduced as a simple method to evaluate faecal fat. The present
      study was aimed at evaluating the acid steatocrit in clinical practice. Faecal
      fat excretion and acid steatocrit results were determined in 42 children, half
      with and half without fat malabsorption. Acid steatocrit results correlated
      significantly with both faecal fat excretion (p < 0.01) and faecal fat
      concentration (p < 0.001). Sensitivity and specificity of the acid steatocrit for
      the diagnosis of malabsorption were 90% and 100%, respectively. We consider the
      acid steatocrit method useful for the screening and monitoring of patients with
      steatorrhoea.

PMID- 9183484
TI  - Nitric oxide and aneurysm formation in Kawasaki disease.
AB  - The objective of this study is to show that nitric oxide plays a role in the
      development of coronary artery abnormalities in Kawasaki disease. We examined
      nitrite+nitrate, biopterin and neopterin in 316 urine samples of 34 patients with
      Kawasaki disease, those of 24 patients with other diseases, and those of 25
      healthy children acting as a control group, because urinary nitrite + nitrate are
      reportedly useful as markers of nitric oxide generation in vivo, and pathways for
      neopterin-biopterin synthesis and nitric oxide generation are tightly coupled. In
      our study, the children with Kawasaki disease excreted more urinary nitrite +
      nitrate and neopterin than did the healthy control group children and excreted
      abnormally high quantities more often than did the patients with other diseases.
      Good relationships were found between the urinary nitrite + nitrate levels and
      the urinary biopterin levels, and between these biopterin levels and the urinary
      neopterin levels. Nitric oxide is therefore thought to be generated in abnormally
      high quantities, and to be closely related to the pathology of Kawasaki disease
      and to the development of coronary artery abnormalities. The role of nitric oxide
      in Kawasaki disease should be further studied to elucidate the pathophysiology of
      the disease and to aid in the development of new treatments.

PMID- 9183485
TI  - Diagnosis of hypoglycaemia: effects of blood sample handling and evaluation of a
      glucose photometer in the low glucose range.
AB  - Hypoglycaemia is a dangerous condition. Rapid and reliable blood glucose
      measurements are necessary for the initiation of treatment to reduce the risk of
      neurological sequelae. The aim of this study was to compare a bedside glucose
      photometer (HemoCue) with three methods of handling blood glucose measurements in
      a routine chemistry laboratory and to estimate the reliability of glucose
      measurements in the low glucose range during controlled hypoglycaemia. Nine
      children underwent an arginine-insulin tolerance test as part of a growth hormone
      deficiency investigation. Only blood samples below 4.0 mmol l-1 were included (n
      = 35). Significant (0.3-1.0 mmol l-1) differences in blood glucose measurements
      were found, depending on the handling of the blood sample. The differences seem
      primarily to be due to glycolysis which occurred in spite of the addition of the
      glycolysis inhibitor NaF to the blood samples. Immediate centrifugation and
      analysis of the supernatant or immediate analysis with the HemoCue results in
      higher, and presumably more correct, values than routine procedures and permits a
      more accurate diagnosis of hypoglycaemia.

PMID- 9183486
TI  - Linear growth in early treated children with congenital hypothyroidism.
AB  - Length/height was studied from birth to 6 years of age in 103 children with
      congenital hypothyroidism identified by the Norwegian or Swedish screening
      programs. We used the "infancy-childhood-puberty (ICP) growth model". This model
      describes normal linear growth during the first 3 years of life by an infancy
      component with the addition of a childhood component, the latter acting from the
      second half of the first year. In comparison with reference children, children
      with hypothyroidism had reduced growth from 6 to 12 months, and increased growth
      after 12 months of age. Mean onset of the childhood component of growth was
      delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9
      months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood
      component was correlated with age at start of treatment (r = 0.24), and in
      children with more severe hypothyroidism (pretreatment serum thyroxine < 40
      nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r =
      -0.40). Change in height standard deviation score from 1 to 3 years of age was
      correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The
      delay in the onset of the childhood component of growth and the association with
      age at start of treatment and initial L-thyroxine dose indicate that thyroid
      hormones during the first months of life are essential for normal onset of the
      childhood component of growth, which otherwise is assumed to be growth hormone
      dependent.

PMID- 9183487
TI  - Treatment of adrenoleukodystrophy with bone marrow transplantation.
AB  - Three children with adrenoleukodystrophy (ALD) underwent allogeneic bone marrow
      transplantation (BMT) between 1992 and 1993. The first boy had attention
      deficits, marked neuropsychological deficits and widespread demyelination in the
      frontal lobes on MRI before transplantation. Four years later he has mentally
      deteriorated and the demyelination on MRI has progressed. The second boy had no
      symptoms but had white matter lesions on MRI when diagnosed. He was regularly
      followed with MRI and neuropsychological investigations until BMT 18 months
      later. A progress of the lesions was noted on the initial MRI investigations, and
      4 months before BMT a worsening of deficits in attention and kinaesthetic praxis
      could be observed. He rapidly deteriorated after the transplantation and died 18
      months later. Both PCR and in situ hybridization confirmed the presence of donor
      cells in the brain. The third boy had no symptoms but white matter lesions on MRI
      when diagnosed. The neuropsychological tests remained normal but a slight
      progress was observed on MRI just before transplantation. This boy is still
      healthy 3.5 years after BMT. BMT as treatment for ALD has to be considered very
      early, even if a child without symptoms but signs of demyelination on MRI, if a
      suitable donor is available.

PMID- 9183488
TI  - Thalamic lesions revealed by MR associated with periventricular leukomalacia and
      clinical profiles of subjects.
AB  - Magnetic resonance (MR) findings at the cerebral white matter and the thalamus in
      44 children with spastic cerebral palsy born at preterm were analysed.
      Periventricular leukomalacia (PVL) was found in all of the children. Lesions of
      the thalamus were revealed in 22 children, 19 of which were in the anterior part
      of the pulvinar and 3 of which were in other areas. Gestational ages and
      birthweights of the children with a lesion of the pulvinar were significantly
      greater than those without lesions of the thalamus. Mental retardation and
      paroxysmal ocular downward deviation were more frequently seen in the children
      with a lesion of the pulvinar than in those without lesions of the thalamus. The
      children with thalamic lesions in areas other than the pulvinar showed the most
      severe motor and mental disabilities.

PMID- 9183489
TI  - Newborn screening strategy for cystic fibrosis: a field study in an area with
      high allelic heterogeneity.
AB  - To verify to what extent mutation analysis on blood spot could improve cystic
      fibrosis neonatal screening in an area with high allelic heterogeneity, we
      designed a special protocol. Spot trypsin estimation at birth, trypsin re-testing
      after 1 month, meconium lactase testing and mutation analysis of delta F508,
      R1162X and N1303K, were retrospectively clustered according to different patterns
      (trypsin/lactase/mutation; trypsin/lactase/re-testing; trypsin/mutation) and
      compared. The programme, which lasted 2 years (1993-94) and covered most of North
      eastern Italy, included 95,553 screened newborns. Thirty-four affected babies
      were detected by screening and one by meconium ileus (incidence 1/2730). The
      combined use of trypsin, lactase and mutation analysis in cystic fibrosis
      neonatal screening permits a better sensitivity compared to the two other
      combinations (34 diagnoses vs 32 in both cases). Moreover, the higher specificity
      of the former method (false positives 42 vs 148) allows a reduction of recalls,
      which cause considerable anxiety. We confirm in trypsin-positive newborns an
      increased frequency of cystic fibrosis heterozygotes (1/17).

PMID- 9183490
TI  - The Swedish national prospective study on extremely low birthweight (ELBW)
      infants. Incidence, mortality, morbidity and survival in relation to level of
      care.
AB  - In a 2-year (1990-92) prospective national investigation, comprising all
      stillborn and live-born ELBW infants with a birthweight of < or = 1000 g born at
      23 completed weeks of gestation or more, we examined the incidence, neonatal
      mortality, major morbidity and infant survival in relation to level of care and
      place of residence. A total of 633 ELBW infants were live-born, i.e. 0.26% of all
      live-born infants, and 298 were stillborn. The average neonatal mortality was 37%
      and 91% at 23 weeks, 70% at 24 weeks, and 40% at 25 weeks of gestation. Of
      neonatal survivors, 8% had intraventricular haemorrhage grade 3, 10% retinopathy
      of prematurity of stage > or = 3, 2% necrotizing enterocolitis, and 28% were
      oxygen-dependent at a time corresponding to 36 weeks of gestation. In all, 77%
      were treated with mechanical ventilation, whereas 19% survived without, almost
      all of them being CPAP treated. Infant mortality among infants born at level III
      (tertiary centres) was 30%, at level IIa (with full perinatal service) 46% and at
      level IIb (with basic neonatal service) 55%. Only 1% was born at hospital level
      I. Regarding the relation to place of residence, the mortality rates among
      infants residing in the areas served by levels III, IIa and IIb hospitals were
      36%, 45% and 41%, respectively. The referral system thus functioned well, but can
      be improved, and increased perinatal referral, at borderline perinatal viability,
      might provide a better quality of care and a better chance of survival.

PMID- 9183491
TI  - The measurement of knee-heel length in newborn infants using a simple vernier
      calipers.
AB  - OBJECTIVE: To assess the usefulness of a simple vernier calipers for measuring
      knee-heel length in neonates. SUBJECTS AND METHODS: Using a simple vernier
      calipers, knee-heel length was measured five times by 2 observers in 50 babies
      (29M, 21F; mean birthweight 1597 g; median gestational age at birth 29 weeks) at
      a median postnatal age of 11 days. A subgroup of 20 babies had knee-heel length
      measured similarly at weekly intervals for 3 weeks. Corrected gestational age and
      weight were simultaneously recorded. One observer was experienced in using the
      vernier calipers. The precision of the calipers was established using 4 steel
      gauge blocks of varying length (7.62-10.17 cm). RESULTS: The calipers were very
      precise when measuring steel gauge blocks. In babies, there was a downward trend
      across the first 2 measurements for both observers, the measurements stabilizing
      over the last three. Using the final three measurements per baby (n = 50), the
      experienced observer had a mean standard deviation of 0.023 cm and mean
      coefficient of variation 0.23% when measuring an average knee-heel length of 9.99
      cm. The inexperienced observer had a mean standard deviation of 0.057 cm and a
      mean coefficient of variation of 0.56%, when measuring an average knee-heel
      length of 10.14 cm. The inter-observer reliability, measured by the intra-class
      correlation coefficient, was 0.99. The agreement between observers was such that
      one observer measured knee-heel length consistently less (0.15 cm, SD 0.18 cm)
      than the other. The reliability for knee-heel length velocity was lower (R =
      0.85), but agreement between observers was high with an average difference of
      0.016 cm/week. Knee-heel length was significantly correlated (p < 0.001) with
      corrected gestational age (r = 0.85) and with weight (r = 0.96). There was a
      weaker but significant correlation (r = 0.47, p < 0.001) between knee-heel length
      velocity and rate of weight gain (g/day), indicating that weight gain may not
      always be accompanied by an increase in linear growth. CONCLUSION: The
      measurement of knee-heel length by a simple vernier calipers is an accurate,
      reproducible and non-invasive method of assessing short-term linear growth in
      neonates. However, it is recommended that measurements of knee-heel length in a
      individual baby should be made by a single experienced observer.

PMID- 9183493
TI  - The development of the complement system after 28 weeks' gestation.
AB  - OBJECTIVE: To assess the levels and development of the various complement
      components in preterm infants, particularly among those born before 34 weeks'
      gestation. SUBJECTS AND METHODS: We measured the complement system's activities
      (CH50 and AP50) as well as its various components (C1q,r,s, C2-C9, Factor B, and
      properdin) in 25 preterm infants [gestational age (GA) 28-33 weeks], 35 preterm
      infants (GA 34-36 weeks), 50 full-term newborn infants (GA 37-42 weeks), and 49
      healthy adults as control subjects. RESULTS AND CONCLUSIONS: The results of these
      studies are: (i) complement levels and activity were significantly reduced in
      preterm and full-term neonates when compared with adult levels, with the
      exception of C7 which was within the normal range in most infants. C8 and C9 were
      the most markedly reduced at all gestational ages. (ii) Complement levels
      correlated significantly with gestational age, but not with birth-weight, type of
      delivery, or gender. (iii) Between 28 and 33 weeks' gestation, there appeared to
      be almost no development of the complement system.

PMID- 9183492
TI  - Measurement of albumin and low molecular weight proteins in the urine of newborn
      infants using a cotton wool ball collection method.
AB  - OBJECTIVE: The aim of this study was to investigate the inter-relationship
      between urinary excretion of alpha-1-microglobulin (A1M), retinol-binding protein
      (RBP) and albumin in term and premature neonates, with urine collected into
      cotton wool balls and extracted by a novel method. SUBJECTS AND METHODS: Sixty
      four infants were studied on the first day of life; 26 had been born at term (37
      42 weeks gestation) and 38 prematurely (24-28 weeks n = 16, 29-36 weeks n = 22).
      Urine collected into cotton wool balls was analysed following a new detergent
      extraction method, which resulted in a recovery rate of 94-107% for albumin. A1M,
      RBP and creatinine. RESULTS: Urinary protein excretion, expressed as a ratio to
      urinary creatinine, decreased significantly with increasing gestational age (24
      28 weeks, 29-36 weeks, 37-42 weeks: albumin:creatinine ratio mg/mmol mean 96.9,
      31.7, 19.3; A1M:creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP:creatinine
      ratio mg/mmol mean 16.2, 3.8, and < 0.01, below the limit of detection,
      respectively). When results were corrected for birthweight, this gestation
      associated effect was still present for A1M and RBP, but not for albumin. In
      premature infants there was a significant positive correlation between
      A1M:creatinine ratio and RBP:creatinine ratio (r = 0.85), and also between
      albumin and both A1M and RBP (r = 0.82 and 0.77). CONCLUSION: Increased excretion
      of A1M, RBP and albumin at earlier gestational ages is probably due to proximal
      tubular immaturity, although tubular damage and also glomerular dysfunction
      cannot be excluded as possible explanations.

PMID- 9183495
TI  - Increase of staphylococci in neonatal septicaemia: a fourteen-year study.
AB  - All cases of neonatal septicaemia during 1981-94 were studied at Orebro Medical
      Centre Hospital, Sweden. One hundred and thirty-two children fulfilled laboratory
      and clinical criteria for neonatal septicaemia and were included. Staphylococcus
      aureus (n = 41), Group B streptococcus (GBS) (n = 32) and coagulase-negative
      staphylococci (CoNS) (n = 27) were the dominating aetiologies. The annual
      incidence of septicaemia increased significantly, from 2.3 cases during the first
      7-year period to 3.3 per 1000 live births during 1988-94. This increase was
      caused by S. aureus and CoNS, which mainly affected premature children and had an
      onset more than 48 h after delivery. GBS, on the other hand, slightly decreased
      and affected full-term children within 48 h. The overall mortality was 11%. CoNS
      isolated during the latter 7-year period were more resistant to antibiotics than
      those isolated during 1981-87; resistance to methicillin increased from 14 to 45%
      and to gentamicin from 0 to 20%. These changes in aetiology and antibiotic
      susceptibility should be considered when selecting antibiotic treatment in
      neonatal septicaemia.

PMID- 9183494
TI  - Serum lecithin: cholesterol acyltransferase activity and HDL2 and HDL3
      composition in small for gestational age newborns.
AB  - The aim of this study was to determine serum lecithin: cholesterol
      acyltransferase (LCAT) activity in parallel with HDL2 and HDL3 composition in
      cord sera of small for gestational age (SGA) newborns, and to compare them with
      those obtained from appropriate for gestational age (AGA) newborns. LCAT activity
      was assayed by conversion of [3H]cholesterol to labelled cholesteryl ester. HDL2
      and HDL3 were separated by ultracentrifugation. Serum cholesteryl ester,
      apolipoprotein (apo) A-I concentrations and LCAT activity were significantly
      lower (-47%, -18% and -56%, respectively), whereas serum triglyceride amounts
      were twofold higher in SGA newborns than in AGA newborns. In SGA newborns, HDL2
      and HDL3 levels were low, and HDL3 and HDL2 phospholipid and HDL2-cholesteryl
      ester contents were diminished. HDL3-apo A-I, A-II, C-III and E values were lower
      in SGA newborns. In HDL2, apo A-I, A-II and E concentrations were decreased.
      Therefore, in SGA newborns, the reduced LCAT activity was associated with
      quantitative and qualitative changes in HDL2 and HDL3 particles.

PMID- 9183496
TI  - The influence of dietary nucleotides on erythrocyte membrane fatty acids and
      plasma lipids in preterm infants.
AB  - OBJECTIVE: The objective of this study was to evaluate whether a regular formula
      for premature infants supplemented with nucleotides has any influence on plasma
      lipids and erythrocyte membrane fatty acids. METHODS: Preterm infants fed either
      human milk supplemented with human milk protein (HM, n = 14), nucleotide
      supplemented preterm formula (NF, n = 13), or a regular preterm formula (F, n =
      13) were included in the study. The NF was supplemented with 18.2 mg cytidine
      monophosphate/l (CMP), 7.0 mg uridine monophosphate/l (UMP), 6.4 mg adenosine
      monophosphate/l (AMP), 3.0 mg inosine monophosphate/l (IMP) and 3.0 mg guanosine
      monophosphate/l (GMP). RESULTS: There were significantly higher concentrations of
      triglycerides (TG) in infants fed NF compared to those fed F (191.42 +/- 79.58 vs
      108.21 +/- 43.73, p < 0.001, mean +/- SD lipid concentrations, mg/100 ml plasma).
      Infants fed F had significantly lower concentrations of total cholesterol (94.34
      +/- 11.71 vs 115.69 +/- 39.29, p < 0.01) and TG in plasma (108.21 +/- 43.73 vs
      172.27 +/- 68.19, p < 0.001, mean +/- SD lipid concentrations, mg/100 ml plasma)
      when compared to HM-fed infants. There were no significant differences in any of
      the erythrocyte membrane fatty acids and total long-chain polyunsaturated fatty
      acids (LC-PUFA) between NF and F during the study period (6 weeks). Furthermore,
      total LC-PUFA and docosahexaenoic acid (DHA) concentrations in red blood cell
      were not significantly different when infants fed NF were compared to those fed
      HM. In contrast, however, infants fed F had significantly lower concentrations of
      total n-3 LC-PUFA (p < 0.01) and DHA (p < 0.01) than those found in HM-fed
      infants. CONCLUSIONS: These results do not suggest an effect of nucleotides on
      the red blood cell LC-PUFA profile in preterm infants. However, the nucleotides
      may increase the concentrations of triglycerides in plasma.

PMID- 9183497
TI  - Incidence of recurrent intussusception following barium versus air enema.
AB  - The aim of this study was to determine whether using air enema for acute
      intussusception is related to a higher rate of recurrence than other methods of
      treatment. A 10-y (1986-95) retrospective study was performed in a university
      affiliated paediatric division. The overall recurrence rate for 97 patients with
      acute intussusception was 7.8% (10% of whom were treated non-surgically). There
      were no recurrences following the surgical treatment. In matched groups of
      patients, no risk factors were found for recurrence following air vs barium
      enema.

PMID- 9183498
TI  - A relapse of paratyphoid fever after treatment with ciprofloxacin in a child with
      congenital biliary atresia.
AB  - This report describes a relapse of Salmonella paratyphi B infection in a child
      with biliary atresia, following 2 weeks of treatment with ciprofloxacin. The
      recrudescence was complicated by the development of osteomyelitis and was treated
      with chloramphenicol, trimethoprim, ceftriaxone and ampicillin in succession.

PMID- 9183499
TI  - Influence of BCG vaccination on tuberculin reactivity in healthy Turkish school
      children.

PMID- 9183500
TI  - Factors associated with weight change among clients of a residential weight
      control program indicating binge and nonbinge traits.
AB  - The long-term effects of a 12- and 26-day residential weight control program on
      weight change were determined in 187 men and women, 1 to 5 years after treatment.
      Subjects completed a paper/pencil questionnaire assessing current diet, weight
      control techniques, exercise behaviors, behavior modification techniques, binge
      eating, and dieting behavior. General linear modeling was used to investigate the
      association between behaviors maintained posttreatment and current weight among
      subjects who demonstrated behaviors indicative of binge traits (BT) and nonbinge
      traits (NBT). Results indicate that dissimilar variables are predictive of weight
      change in the BT and NBT groups. Engaging in exercise behaviors and reduced
      attempts at dieting lead to greater weight loss in NBT individuals. The use of
      preplaning techniques was found to be indicative of greater weight loss in BT
      individuals. These findings suggest the importance of identifying individuals who
      indulge in binge-eating behaviors prior to intervention in order to deliver the
      appropriate treatment methods.

PMID- 9183501
TI  - Effects of alcohol and expectancy on self-disclosure and anxiety in male and
      female social drinkers.
AB  - To study the effects of alcohol consumption and expectancy on self-disclosure and
      self-reported anxiety during a social interaction, 32 male and 32 female social
      drinkers were assigned to one of four groups comprising a 2 x 2 factorial
      balanced-placebo design. Alcohol expectancy reduced the intimacy level of self
      disclosure but not the amount of self-disclosure. Alcohol consumption had no
      effect. Thus, in contrast to the common view that alcohol functions as a "social
      lubricant," it served to inhibit social interaction. There was a three-way
      interaction among alcohol consumption, expectancy, and gender of subjects, such
      that the largest increase in anxiety was reported by male subjects who expected
      but did not receive alcohol. Thus, the previously reported inverse relationship
      between anxiety and self-disclosure was not confirmed, and alcohol's effect on
      anxiety seems unrelated to its effect on self-disclosure.

PMID- 9183503
TI  - Subtypes within a sample of precontemplating smokers: a preliminary extension of
      the stages of change.
AB  - Precontemplating smokers are not planning to quit within the next 6 months. There
      are indications that this group is not homogeneous. The present investigation
      aimed at identifying relevant subgroups within this large group of smokers in
      order to refine stage-matched interventions. Precontemplators were asked whether
      they were planning to quit (1) within the next year. (2) within the next 5 years,
      (3) not within the next 5 years but sometime, (4) never, or (5) none of the
      above. Smokers who were planning to quit within 5 years (redefined
      precontemplators) differed from smokers who were not planning to quit within the
      next 5 years (immotives) on the pros of quitting but not on self-efficacy scores.
      Compared to smokers in the other groups, immotives scored significantly lower on
      specific factors within the pros of quitting.

PMID- 9183502
TI  - The prevalence and frequency of drug use among Western Australian metropolitan
      high school students.
AB  - Data pertaining to prevalence and frequency of drug use were obtained from 1,394
      Western Australian metropolitan high school students using a self-report
      questionnaire. Alcohol, marijuana, tobacco, hallucinogens, and amphetamines were
      reported as the most prevalent substances, with over 50% of "current drug users"
      using alcohol and marijuana on a frequent basis (i.e., weekly to more than once
      per day). Significant interactions existed between Gender and prevalence of
      tobacco and hallucinogens; and School Year Level and prevalence of tobacco,
      alcohol, hallucinogens and amphetamines. In terms of the frequency of use,
      significant interactions were found between Gender and marijuana; and between
      School Year Level and tobacco. Approximately 40% of substance-using participants
      used one single substance, 40% used two or three substances, and 20% used four or
      more substances. The results suggest there is a need for educators to have a
      greater understanding of the patterns of substance use in order for them to more
      aptly shape drug education programs.

PMID- 9183504
TI  - Decisional balance and stage of change for adolescent drinking.
AB  - The Transtheoretical Model of Change has been proven very effective in explaining
      both the acquisition and cessation of many health related behaviors. In this
      study, this model was applied to the domain of immoderate alcohol use among
      adolescents (usually drinking three or more drinks per occasion). Measures for
      two constructs of the model were developed: Stage of Change and Decisional
      Balance. A total of 853 tenth and eleventh graders who attend vocational training
      programs were administered a 37-item decisional balance questionnaire and a 5
      item staging measure. A short (16-item) psychometrically sound Decisional Balance
      Inventory was developed based on an exploratory factor analysis that identified
      two factors, the Pros and Cons of Alcohol Use. The factor structure was confirmed
      using structural modeling techniques on a hold-out sample. Based on a combination
      of model fit and parsimony considerations, an uncorrelated model was selected
      (IFI2 = .909). Students were classified into one of nine stages of acquisition or
      cessation. External validity was established by the significant and meaningful
      differences between the stages of change on the pros and cons of alcohol use.
      Implications of this research are discussed.

PMID- 9183505
TI  - Multiple predictors of illicit drug use in methadone maintenance clients.
AB  - Many drug users in methadone maintenance treatment continue to use a variety of
      illicit drugs. The present study tested a hierarchical, multidimensional model to
      predict concurrent substance use in methadone maintenance clients. The model
      incorporated measures of demographics, personality, coping, motivation, and
      methadone beliefs. Subjects were 94 male and female injecting drug users in
      methadone treatment. Using multiple regression, results showed that a model
      incorporating all the predictors accounted for 51% of the variance in self
      reported drug use. The study highlights the importance of using multidimensional
      models to study the complex factors involved in drug use.

PMID- 9183506
TI  - Self-directed hostility and family functioning in normal-weight bulimics and
      overweight binge eaters.
AB  - The aim of this study was to examine whether overweight binge eaters demonstrate
      similar perceptions of family interactions and views of the self as do normal
      weight bulimics. We compared 37 obese binge eaters and 37 normal-weight bulimics
      to 38 normal-weight non-bulimic controls, and 10 overweight nonbulimic controls
      on the Bulimia Test (BULIT). Profile of Mood States (POMS), Structural Analysis
      of Social Behavior (SASB) Short Form, which includes measure of hostility of
      family interactions and self-directed hostility; the Family Interaction Survey
      (FIS), and a measure of history of physical and sexual abuse and familial
      psychopathology. Both normal-weight bulimics and overweight binge eaters differed
      from nonbulimic controls across all measures of symptomatology, family
      functioning, history of abuse, familial psychopathology, and self-directed
      hostility. Normal-weight bulimics demonstrated significantly higher BULIT scores
      and self-directed hostility than did overweight binge eaters. Post hoc analysis
      showed that among binge eaters and bulimics, self-directed hostility accounted
      for a significant percentage of the variance of BULIT scores when controlling for
      the effects of age, BMI, family hostility, and mood. The possible role of self
      directed hostility in the maintenance of bulimic symptomatology is discussed.

PMID- 9183507
TI  - Motivation for smoking cessation among the Norwegian public.
AB  - A questionnaire survey among a representative sample of Norwegians (N = 5,014)
      showed that 33% (n = 1,639) smoked. About one-third of the cigarette smokers were
      motivated to quit, and they most frequently wished to be informed about smoking
      cessation methods. Participation in a smoking-cessation group was the variable
      most significantly associated with a general motivation to quit. The Smoking
      Effects Questionnaire (SEQ) tested smokers' perception of smoking consequences.
      Two SEQ dimensions significantly affected general motivation. Women tended to
      emphasize the effect of smoking on physical appearance, whereas men were more
      concerned about their health.

PMID- 9183508
TI  - Drinking location and risk of alcohol-impaired driving among high school seniors.
AB  - This study investigated environmental predictors of teenagers' alcohol-impaired
      driving, such as drinking location and alcohol source. Data for this study were
      part of the 15 Communities Mobilizing for Change on Alcohol Project.
      Relationships between drinking-driver status, alcohol source, drinking location,
      alcohol consumption, and individual demographics were determined for the full
      sample as well as for males and females separately, using mixed-model, logistic
      regression. Analyses were restricted to high school seniors who were drivers and
      who consumed alcohol within the last 30 days (N = 1,914). For males and females,
      the risk of alcohol-impaired driving rose significantly with increases in both
      the number of binge-drinking events and estimates of the number of drinks
      required to impair their driving. Drinking location was important in that
      students who drank outdoors or in a moving car or truck were at significant risk
      for drinking-driving. Drinking-driving risks specific to females were number of
      drinking occasions and drinking at someone else's house. Strategies to prevent
      drinking-driving among teenagers need to consider drinking patterns as well as
      drinking locations for both males and females.

PMID- 9183509
TI  - Cue reactivity to food- and body-related stimuli in restrained and unrestrained
      eaters.
AB  - In the present study, psychophysiological cue reactivity was monitored in 11
      restrained (nonclinical but disinhibitive) and 13 unrestrained (control)
      subjects. The cues consisted of slides depicting either personally "favourite"
      binge food items or the subject's own body. The parameters monitored included
      skin conductance, heart rate, startle eyeblink EMG, and facial (corrugator and
      zygomatic) EMG. Although for several parameters the expected main effect of slide
      type was found, no between-group differences in cue reactivity could be
      demonstrated. Several explanations of the present finding, as well as possible
      future directions for cue reactivity research, are discussed, with emphasis
      placed upon the role of classical conditioning in eating disorders.

PMID- 9183510
TI  - Relapse prevention treatment for cocaine dependence: group vs. individual format.
AB  - To investigate the role of treatment modality in relapse prevention treatment, 32
      cocaine-dependent subjects were randomly assigned by cohorts to group-based
      relapse prevention (G-RP) or individually based RP (I-RP). The two RP formats
      were identical in content, consisting of 12 outpatient treatment sessions over a
      2-month period immediately following hospitalization. The proportion of subjects
      providing cocaine-free urines at the end of RP treatment did not differ between
      formats; however, G-RP subjects reported using cocaine on significantly fewer
      days during treatment, and experiencing fewer cocaine-related problems than did I
      RP subjects. Follow-up data collected at 12 and 24 weeks' posttreatment revealed
      no significant differences between RP formats on any cocaine-use outcome
      measures. Regardless of therapy format. RP treatment was related to statistically
      significant and sustained improvements in other areas of psychosocial
      functioning, including addiction severity, coping, and craving for cocaine. The
      overall findings suggest that the efficacy of relapse prevention training is not
      limited by therapy format.

PMID- 9183511
TI  - Social competence in opiate-addicted individuals: gender differences,
      relationship to psychiatric diagnoses, and treatment response.
AB  - Only one prior study has examined social competence (SC) in drug addicted
      individuals. That study of cocaine-addicted individuals found gender differences
      in SC as well as differences based on the type of comorbid psychiatric diagnoses
      given. This study attempts to replicate findings from that cocaine study in a
      sample of opiate-addicted individuals and explores the relationship of SC to
      short-term treatment response. Gender differences in SC were examined in 28 women
      and 44 men attending a community methadone maintenance program. The question of
      differences in SC based on comorbid psychiatric diagnoses and treatment response
      were examined in a sample of 198 men attending a Veterans Administration
      methadone program. Women were found to have significantly lower SC than men. No
      significant differences in SC were revealed based on the presence of specific
      psychiatric diagnoses. SC was not related to short-term treatment response.

PMID- 9183512
TI  - Long-term trends in cigarette smoking among young U.S. adults.
AB  - Retrospective examination of a national probability sample revealed that young
      women, particularly those who dropped out of high school, have reached smoking
      rates as high or higher than subgroups of young men. These results suggest that
      surveillance, research, and public health programs are needed to address the
      rapid increase in smoking among young women.

PMID- 9183513
TI  - Targeted naltrexone treatment of early problem drinkers.
AB  - Naltrexone is approved for daily use in the treatment of alcohol dependence. We
      evaluated the feasibility of using targeted naltrexone (i.e., on an "as-needed"
      basis) to treat early problem drinkers. Twenty-one subjects (52% male) received
      brief coping skills training weekly for 4 weeks, along with naltrexone (50 mg),
      which they were instructed to use 2 to 5 times per week in anticipation of high
      risk drinking situations. During treatment, statistically and clinically
      significant declines were observed across a variety of drinking-related outcomes,
      including the intensity of drinking, the decline in which was correlated with
      medication use. Beneficial effects of the intervention were still evident during
      the 3-month posttreatment period. Further research, including a placebo
      controlled evaluation of targeted naltrexone, is needed to determine the optimal
      treatment strategy for early problem drinkers, many of whom are seen in the
      primary-care medical setting.

PMID- 9183514
TI  - Interdependence of the endocrine and immune systems.
AB  - The cross-talk involving the endocrine and immune systems is now largely
      established. These systems actually use similar ligands and receptors to
      establish a physiological intra- and inter-system communication circuitry, which
      apparently plays a relevant role in homeostasis (reviewed in Blalock, 1992).
      Accordingly, classical hormones such as prolactin (PRL), growth hormone (GH) and
      even glucocorticoids (GC) can be produced by cells of the immune system, whereas
      a variety of cytokines, originally described as being produced by cells of the
      immune system, are synthesized and released by a variety of endocrine glands and
      nervous tissue. Moreover, specific receptors for such distinct molecular families
      can be detected in both the immune and endocrine systems.

PMID- 9183515
TI  - Biology of the congenitally hypothyroid hyt/hyt mouse.
AB  - The hyt/hyt mouse has an autosomal recessive, fetal onset, characterized by
      severe hypothyroidism that persists throughout life and is a reliable model of
      human sporadic congenital hypothyroidism. The hypothyroidism in the hyt/hyt mouse
      reflects the hyporesponsiveness of the thyroid gland to thyrotropin (TSH). This
      is attributable to a point mutation of C to T at nucleotide position 1666,
      resulting in the replacement of a Pro with Leu at position 556 in transmembrane
      domain IV of the G protein-linked TSH receptor. This mutation leads to a
      reduction in all cAMP-regulated events, including thyroid hormone synthesis. The
      diminution in T3/T4 in serum and other organs, including the brain, also leads to
      alterations in the level and timing of expression of critical brain molecules,
      i.e. selected tubulin isoforms (M beta 5, M beta 2, and M alpha 1), microtubule
      associated proteins (MAPs), and myelin basic protein, as well as to changes in
      important neuronal cytoskeletal events, i.e. microtubule assembly and SCa and SCb
      axonal transport. In the hyt/hyt mouse, fetal hypothyroidism leads to reductions
      in M beta 5, M beta 2, and M alpha 1 mRNAs, important tubulin isoforms, and M
      beta 5 and M beta 2 proteins, which comprise the microtubules. These molecules
      are localized to layer V pyramidal neurons in the sensorimotor cortex, a site of
      differentiating neurons, as well as a site for localization of specific thyroid
      hormone receptors. These molecular abnormalities in specific cells and at
      specific times of development or maturation may contribute to the observed
      neuroanatomical abnormalities, i.e. altered neuronal process growth and
      maintenance, synaptogenesis, and myelination, in hypothyroid brain. Abnormal
      neuroanatomical development in selected brain regions may be the factor
      underlying the abnormalities in reflexive, locomotor, and adaptive behavior seen
      in the hyt/hyt mouse and other hypothyroid animals.

PMID- 9183516
TI  - Autoimmunity to the thyroid stimulating hormone receptor.
AB  - Thyroid disorders are the most common endocrine diseases and affect a large
      segment of the population. Most of the thyroid diseases are autoimmune in nature
      and can be broadly grouped into two categories; one mediated by autoimmune
      responses to the thyroglobulin (i.e. Hashimoto's thyroiditis), and the other
      mediated by autoimmunity to the thyrotropin receptor (primarily Graves' disease).
      Although patients with autoimmune thyroid diseases exhibit immune responses
      against a number of thyroid antigens, such as thyroglobulin, thyrotropin receptor
      and thyroid peroxidase, responses directed against a specific antigen appear to
      play an important role in the disease pathogenesis. For example, Hashimoto's
      thyroiditis is primarily mediated by T cell responses directed toward the
      thyroglobulin receptor, whereas Graves' disease is mediated by antibodies
      directed against the thyrotropin receptor. In this review we will focus on
      thyroid diseases mediated by autoimmune responses to the thyrotropin receptor.

PMID- 9183517
TI  - Cytokines and thyroid function.
AB  - Cytokines play a crucial role in autoimmune thyroid disease (ATD) through various
      mechanisms. They are produced in the thyroid by intrathyroidal inflammatory
      cells, in particular lymphocytes, as well as by the thyroid follicular cells
      (TFC) themselves and may thus act in a cascade to enhance the autoimmune process
      (Fig. 1). Cytokines upregulate the inflammatory reaction through stimulation of
      both T and B cells, resulting in antibody production and tissue injury. In
      addition, intrathyroidal cytokines induce immunological changes in TFC including
      enhancement of both major histocompatibility complex (MHC) class I and class II
      molecule expression, and upregulation of adhesion and complement regulatory
      molecule expression. Cytokines can also modulate both growth and function of TFC
      and have a role in extrathyroidal complications of ATD, most importantly thyroid
      associated ophthalmopathy (TAO), where they induce fibroblast proliferation and
      enhance the production of glycosaminoglycans (GAG), resulting in proptosis and
      the other clinical features of the disease. In addition to these effects,
      exogenous administration of cytokines has been associated with impairment of
      thyroid function ranging from the appearance of autoantibodies alone to the
      development of frank thyroid dysfunction. Cytokines have also been implicated in
      subacute thyroiditis (SAT) and amiodarone-induced thyroid dysfunction, as well as
      in thyroid function abnormalities occurring in patients with non-thyroidal
      illnesses (NTI). Genetic variations in cytokine genes represent potential risk
      factors for ATD, and disease associations have been described for polymorphisms
      in IL-1ra and TNF beta genes. Recent experimental evidence suggests the
      possibility of novel cytokine-based therapeutic approaches for ATD and its
      complications, in particular TAO.

PMID- 9183518
TI  - Immunomodulation of peripheral lymphocytes by hormones of the hypothalamus
      pituitary-thyroid axis.
AB  - The aim of this review is to provide a comprehensive examination of the current
      literature describing the immunoregulatory effects on the peripheral immune
      system by the hormones that comprise the hypothalamic-pituitary-thyroid (HPT)
      axis. This article discusses the effects of the HPT axis hormones on the
      peripheral lymphoid tissues and the immune responses mediated by the cells that
      comprise these lymphoid tissues. Neuroendocrine dysfunction in the HPT axis,
      either naturally or experimentally induced, and the resulting immune dysfunction
      are also discussed. Emphasis in this article is placed on the most recent study
      findings and those that provide a unique or novel way of evaluating HPT hormone
      effects on the immune system. Our knowledge of the immunoregulatory effects of
      the hormones that comprise the HPT axis has grown tremendously in the last 10
      years. As can be seen in this review, the immunoregulatory effects of the HPT
      axis hormones are quite diverse and influence most, if not all, aspects of immune
      system physiology. The continued exploration of the bidirectional circuitry
      between the immune and neuroendocrine systems may allow for development of
      appropriate prophylactic procedures that prevent dysfunction in both systems.

PMID- 9183519
TI  - T cell development within the intestinal mucosa: clues to a novel immune
      endocrine network?
AB  - Small intestine intraepithelial lymphocytes (IELs) comprise a heterogeneous and
      phenotypically complex population of T cells that are part of the gut-associated
      lymphoid tissues (GALTs). Recent studies from a number of laboratories indicate
      that murine IELs are greatly enriched for extrathymic T cells, although many
      aspects of the IEL extrathymic developmental pathway remain controversial, and
      there is currently no consensus of opinion as to which IELs are extrathymic and
      which are thymus-derived. Those differences reflect variations in the IEL
      repertoire in athymic animals depending upon the specific model used to study
      IELs, and they correlate with the age at which mice became or were rendered
      athymic, implying that the thymus participates either directly or indirectly in
      the local extrathymic IEL developmental process. In this article, the basic
      findings regarding intestinal T cell development are discussed, and a hypothesis
      is provided which links neuroendocrine interactions targeted to the intestine
      epithelium to the striking relationship between animal developmental age and the
      thymopoietic potential of the intestine.

PMID- 9183520
TI  - Dynamic regulation of intestinal immunity by hormones of the hypothalamus
      pituitary-thyroid axis.
AB  - The role of the thymus in the development of murine small intestinal
      intraepithelial lymphocytes (IELs) has been a controversial topic for decades.
      This controversy has been further propagated by observations that differences in
      IEL repertoires vary according to the particular athymic animal model system used
      to study IELs. In an attempt to understand the bases for these differences, we
      have undertaken a series of experiments designed to explore the extent to which
      extraimmunologic events, in particular neuroendocrine factors, play a role in the
      development of extrathymic IELs. As discussed here, these studies indicate that
      hormones of the hypothalamus-pituitary-thyroid (HPT) axis exert either positive
      or negative regulatory effects on intestinal IELs, depending upon the particular
      hormone. Although the mechanisms by which HPT hormones influence IEL development
      and immune regulation have yet to be fully delineated, it appears that thyroid
      stimulating hormone is a key mediator in this process, and that this may occur
      via local autocrine/paracrine responses within the intestine itself. The
      implications of these findings in the context of immunity and disease at the
      level of the gastrointestinal tract are discussed.

PMID- 9183521
TI  - Aging, immunity and neuroendocrine hormones.
AB  - Recent evidence indicates that the neuroendocrine and immune systems are
      intimately integrated into one system that provides a complex homeostatic
      network. Disruption of one system by extrinsic factors such as stress or
      antigenic exposure usually has consequences on the other. With advancing age, a
      progressive disruption can be observed in both systems which may have profound
      implications with respect to age-associated pathologies, including autoimmunity.
      In this review evidence is summarized which supports the hypothesis that
      neuroendocrine factors influence the age-associated decline of the immune system.

PMID- 9183522
TI  - An iterative algorithm for converting a class II MHC binding motif into a
      quantitative predictive model.
AB  - Biochemists and molecular biologists have suggested motifs for characterizing the
      binding of peptide fragments and class II major histocompatibility complex (MHC)
      molecules based on laboratory results and crystal structures. The iterative
      algorithm presented here converts a suggested motif into a quantitative data
      based model. The database accessed consists of peptide fragments known to bind or
      not bind to class II MHC molecules of particular haplotypes. Stepwise
      discriminant analysis is utilized to increase or decrease motif coefficients
      until the resulting motif classifies all binders and non-binders correctly.
      Stepwise discriminant analysis is a standard multivariate statistical procedure
      and is available in comprehensive commercial statistical packages. Program 7M of
      BMDP Statistical Software was used in this study.

PMID- 9183523
TI  - Mapdiff: determining differences between two genomic maps.
AB  - MOTIVATION: When inspecting two maps of a chromosome or chromosomal region
      derived by similar or different methodologies, a computer-generated description
      of their differences is valuable, both to guide laboratory research as well as to
      assist version control. Our program, Mapdiff, can be used to compare two
      independently derived maps, or two revisions of the same map. Its usefulness
      increases in proportion to the percentage of shared objects between the two maps.
      Mapdiff uses a greedy algorithm to determine differences between shared objects.
      RESULTS: We illustrate Mapdiff's use in comparing the publicly available STS
      content and radiation hybrid maps of human chromosome 12. AVAILABILITY: Freely
      available, (source, executables for Windows/DOS and Sun Solaris, documentation)
      on request from the author.

PMID- 9183524
TI  - Construction of evolutionary distance trees with TREECON for Windows: accounting
      for variation in nucleotide substitution rate among sites.
AB  - MOTIVATION: To improve the estimation of evolutionary distances between
      nucleotide sequences by considering the differences in substitution rates among
      sites. RESULTS: TREECON for Windows (Van de Peer,Y. and De Wachter,R. Comput.
      Applic. Biosci., 9, 569-570, 1994) is a software package for the construction and
      drawing of phylogenetic trees based on distance data computed from nucleic acid
      and amino acid sequences. For nucleic acids, we here describe the implementation
      of a recently developed method for estimating evolutionary distances taking into
      account the substitution rate of individual sites in a sequence alignment.
      AVAILABILITY: TREECON for Windows is available on request from the authors. A
      small fee is asked in order to support the work and to reinvest in new computer
      hard- and software. More information about the program and substitution rate
      calibration can be found at URL http:/(/)bioc-www.uia.ac.be/u/
      yvdp/treeconw.html.

PMID- 9183526
TI  - Seq-Gen: an application for the Monte Carlo simulation of DNA sequence evolution
      along phylogenetic trees.
AB  - MOTIVATION: Seq-Gen is a program that will simulate the evolution of nucleotide
      sequences along a phylogeny, using common models of the substitution process. A
      range of models of molecular evolution are implemented, including the general
      reversible model. Nucleotide frequencies and other parameters of the model may be
      given and site-specific rate heterogeneity can also be incorporated in a number
      of ways. Any number of trees may be read in and the program will produce any
      number of data sets for each tree. Thus, large sets of replicate simulations can
      be easily created. This can be used to test phylogenetic hypotheses using the
      parametric bootstrap. AVAILABILITY: Seq-Gen can be obtained by WWW from
      http:/(/)evolve.zoo.ox.ac.uk/Seq-Gen/seq-gen.html++ + or by FTP from
      ftp:/(/)evolve.zoo.ox.ac.uk/packages/Seq-Gen/. The package includes the source
      code, manual and example files. An Apple Macintosh version is available from the
      same sites.

PMID- 9183525
TI  - 'TransMem': a neural network implemented in Excel spreadsheets for predicting
      transmembrane domains of proteins.
AB  - MOTIVATION: Genomic sequences from different organisms, even prokaryotic, have
      plenty of orphan ORFs, making necessary methods for the prediction of protein
      structure and function. The prediction of the presence of hydrophobic
      transmembrane (HTM) stretches is a valuable clue for this. RESULTS: The program.
      TransMem, based on a neural network and running on personal computers (either
      Apple Macintosh or PC, using Excel worksheets), for the prediction and
      distribution of amino acid residues in transmembrane segments of integral
      membrane proteins is reported. The percentage of residue predictive accuracy
      obtained for the set of proteins tested is 93%, ranging from 99.9% for the best
      to 71.7% for the worst prediction. The segment-based accuracy is 93.6%; 63.6% of
      the protein set match any of the predicted and observed segment locations.
      AVAILABILITY: TransMem is available upon request or by anonymous up: IP address:
      luz.uab.es, directory/pub/ TransMem. It is also placed on the EMBL file server
      (ftp:/(/)ftp.ebi.ac.uk/pub/software/mac/TransMem ).

PMID- 9183527
TI  - Grouper--creation of marker sets for multiplexed genotyping.
AB  - MOTIVATION: Efficient high-throughput genotyping experiments require the
      multiplexing of polymorphic markers, i.e. the use of multiple markers with non
      overlapping allele size ranges in a single lane of a genotyping gel. The
      arrangement of such markers into sets can be facilitated by the availability of
      appropriate computer software. RESULTS: This article describes a program,
      Grouper, that automates the generation of marker sets for multiplexed genotyping
      experiments. AVAILABILITY: The software described in this article is available
      free of charge from the EBI software archive at
      (ftp://ftp.ebi.ac.uk/pub/software/unix).

PMID- 9183528
TI  - ProMSED: protein multiple sequence editor for Windows 3.11/95.
AB  - MOTIVATION: Most protein sequence alignment algorithms give similar results on
      closely related proteins, while manual intervention may be needed for distantly
      related molecules. To correct the alignment, it is often necessary to repeat
      calculations on selected parts of the alignments and edit the alignment manually.
      Software implementing such interactive alignment procedures is of significance.
      RESULTS: This paper presents a new MS Windows application called ProMSED for both
      automatic and manual protein sequence alignment. The program reads main sequence
      formats and has a user-friendly interface. ProMSED performs automatic (ClustalV
      algorithm) alignments, alignment visualization and editing, and it allows
      sequences to be aligned interactively leaving previously aligned regions
      unchanged. Manual alignment and sequence analysis are facilitated by colouring
      schemes reflecting amino acid similarity of mutational and physicochemical
      properties. The interactive alignment of a diverged set of reverse transcriptases
      has located four out of six known conserved motifs. AVAILABILITY: ProMSED is
      available on request from the authors. DEMO is available from
      ftp://ftp.ebi.ac.uk/pub/ software/dos/promsed/ or
      ftp://iubio.bio.indiana.edu/molbio/ ibmpc/.

PMID- 9183529
TI  - Match-Box_server: a multiple sequence alignment tool placing emphasis on
      reliability.
AB  - MOTIVATION: The Match-Box software comprises protein sequence alignment tools
      based on strict statistical thresholds of similarity between protein segments.
      The method circumvents the gap penalty requirement: gaps being the result of the
      alignment and not a governing parameter of the procedure. The reliable conserved
      regions outlined by Match-Box are particularly relevant for homology modelling of
      protein structures, prediction of essential residues for site-directed
      mutagenesis and oligonucleotide design for cloning homologous genes by polymerase
      chain reaction (PCR). RESULTS: The method produces reliable results, as assessed
      by tests performed on protein families of known structures and of low sequence
      similarity. A reliability score is computed in relation to a threshold of
      similarity progressively raised to extend the aligned regions to their maximal
      length, up to the significance limit of matching segments. The score obtained at
      each position is printed below the sequences and allows a discriminant reading of
      each aligned region. AVAILABILITY: Sequences may be submitted to a Web server at
      http://www.fundp.ac.be/sciences/biologie/bms/+ ++matchbox_submit.html or sent by
      e-mail to matchbox/biq.fundp.ac.be (help available by just mailing help).

PMID- 9183530
TI  - Object-oriented developmental environment for image-analysis applications:
      implementation for 2D gel electrophoretogram analysis.
AB  - MOTIVATION: The principal motivation was to design an environment for the
      development of image-analysis applications which would allow the integration of
      independent modules into one frame and make available tools for their build-up,
      running, management and mutual communication. RESULTS: The system was designed as
      modular, consisting of the core and work modules. The system core focuses on
      overall management and provides a library of classes for build-up of the work
      modules, their user interface and data communication. The work modules carry
      practical implementation of algorithms and data structures for the solution of a
      particular problem, and were implemented as dynamic-link libraries. They are
      mutually independent and run as individual threads, communicating with each other
      via a unified mechanism. The environment was designed to simplify the development
      and testing of new algorithms or applications. An example of implementation for
      the particular problem of the analysis of two-dimensional (2D) gel
      electrophoretograms is presented. The environment was designed for the Windows NT
      operating system with the use of Microsoft Foundation Class Library employing the
      possibilities of C++ programming language. AVAILABILITY: Available on request
      from the authors.

PMID- 9183531
TI  - Prediction of probable genes by Fourier analysis of genomic sequences.
AB  - MOTIVATION: The major signal in coding regions of genomic sequences is a three
      base periodicity. Our aim is to use Fourier techniques to analyse this
      periodicity, and thereby to develop a tool to recognize coding regions in genomic
      DNA. RESULT: The three-base periodicity in the nucleotide arrangement is
      evidenced as a sharp peak at frequency f = 1/3 in the Fourier (or power)
      spectrum. From extensive spectral analysis of DNA sequences of total length over
      5.5 million base pairs from a wide variety or organisms (including the human
      genome), and by separately examining coding and non-coding sequences, we find
      that the relative-height of the peak at f = 1/3 in the Fourier spectrum is a good
      discriminator of coding potential. This feature is utilized by us to detect
      probable coding regions in DNA sequences, by examining the local signal-to-noise
      ratio of the peak within a sliding window. While the overall accuracy is
      comparable to that of other techniques currently in use, the measure that is
      presently proposed is independent of training sets or existing database
      information, and can thus find general application. AVAILABILITY: A computer
      program GeneScan which locates coding open reading frames and exonic regions in
      genomic sequences has been developed, and is available on request.

PMID- 9183532
TI  - A Brownian dynamics model for the chromatin fiber.
AB  - MOTIVATION: We describe a Brownian dynamics model for the folding of the
      chromatin fiber based on the model of Woodcock et al. (Proc Natl Acad Sci USA,
      90, 9021-9025, 1993). The model takes into account the elastic properties of the
      DNA as well as the electrostatic interaction and nucleosomal excluded-volume
      interaction. The solvent is described as a viscous medium, the electrostatic
      interactions by a screened Coulomb potential. RESULTS: The hydrodynamic
      properties and their dependence on the solvent's ionic strength are accurately
      reproduced by the model for nucleosome di- and tetramers. Ionic strength
      dependent changes in mobility can be attributed to partial screening of the
      electrostatic repulsion between different segments of linker DNA. Formation of
      fiber-like structures occurs on time scales of several hundred microseconds for a
      linear configuration of 25 nucleosomes. The model was implemented by creating
      user-defined data types. Use of this so-called object-oriented paradigm allowed
      for a high degree of component reuse in simulation, analysis and visualization
      contexts. AVAILABILITY: The described software is available on request from the
      authors. Additional information can be found on the WWW at http:/(/)www.dkfz
      heidelberg.de/Macromol/ehrlich /chromatin.htm/.

PMID- 9183533
TI  - Using explicitly represented biological relationships for database navigation and
      searching via the World-Wide Web.
AB  - MOTIVATION: The increasing availability of biological databases on the World-Wide
      Web and hypertext links between them has made a wealth of information easily
      accessible to biologists. Additional retrieval capabilities can be achieved by
      storing explicitly specified biological relationships between different entities
      as discrete database entries. RESULTS: We have built CySPID, a prototype database
      about the cytoskeleton that explores the approach of explicitly representing
      biological relationships. The stored relationships are displayed along with other
      retrieved information, can be used to make hyperlinks to related entities, and
      can be used to search for entities with specified properties. CySPID is
      extensible in that new types of relationships may be created without altering the
      database schema. AVAILABILITY: CySPID is available for public use
      (http://ycmi.med.yale.edu/cyspid/). The CGI scripts used by CySPID are available
      upon request.

PMID- 9183534
TI  - P-SEA: a new efficient assignment of secondary structure from C alpha trace of
      proteins.
AB  - MOTIVATION: The secondary structure is a key element of architectural
      organization in proteins. Accurate assignment of the secondary structure elements
      (SSE) (helix, strand, coil) is an essential step for the analysis and modelling
      of protein structure. Various methods have been proposed to assign secondary
      structure. Comparative studies of their results have shown some of their
      drawbacks, pointing out the difficulties in the task of SSE assignment. RESULTS:
      We have designed a new automatic method, named P-SEA, to assign efficiently
      secondary structure from the sole C alpha position. Some advantages of the new
      algorithm are discussed. AVAILABILITY: The program P-SEA is available by
      anonymous ftp: ftp.lmcp.jussieu.fr directory: pub/.

PMID- 9183535
TI  - The role of long-range interactions in defining the secondary structure of
      proteins is overestimated.
AB  - MOTIVATION: Secondary structure predictions based on the properties of individual
      residues, and sometimes on local interactions, usually fail to exceed 65%
      efficiency. Therefore, non-local, long-range interactions seem to be a
      significant cause of this limitation. RESULTS: In this paper, we apply approaches
      to localize highly interacting residues and clusters of residues involved in
      multiple non-local interactions, and test various secondary structure predictions
      on this separate subset to assess the effect of long-range interactions on the
      prediction efficiencies. It was found that only a marginal part of the failure of
      secondary structure predictions results from the presence of long-range
      interactions. Alternative possibilities are also discussed.

PMID- 9183536
TI  - End-Epi: an application for inferring phylogenetic and population dynamical
      processes from molecular sequences.
AB  - MOTIVATION: Phylogenetic trees constructed from molecular sequences contain
      information about the evolutionary or population dynamical processes that created
      them. Here we describe a computer package (End-Epi) that uses graphical methods
      to allow researchers to make inferences about these processes from their data.
      Statistical analyses can be performed to test the consistency of the data with
      various competing hypotheses. AVAILABILITY: End-Epi can be obtained by WWW from
      http://evolve.zoo.ox.ac.uk/ and by anonymous FTP from
      ftp://evolve.zoo.ox.ac.uk/packages/End-Epi10.hqx. This file contains the compiled
      application, the manual and a test tree.

PMID- 9183537
TI  - DnaSP version 2.0: a novel software package for extensive molecular population
      genetics analysis.
AB  - MOTIVATION: Several methods in molecular population genetics have recently been
      described to estimate the amount and pattern of the DNA polymorphism in natural
      populations, and also to test the neutral theory of molecular evolution. These
      methods are essential for understanding the molecular evolutionary process.
      However, a comprehensive computer program for the analysis is not currently
      available. RESULTS: Here we present DnaSP (DNA Sequence Polymorphism) version
      2.0, a software package for Windows that performs extensive population genetics
      analyses on DNA sequence data. DnaSP estimates several measures of DNA sequence
      variation within and between populations, linkage disequilibrium, recombination,
      gene flow and gene conversion (a new algorithm to detect gene conversion tracts
      has been included). DnaSP can also carry out several tests of neutrality: those
      of Fu and Li; Hudson, Kreitman and Aguade; and Tajima. The results of the
      analyses are displayed in tabular and graphic form. AVAILABILITY: For academic
      uses, DnaSP is available via anonymous ftp: ftp.ebi.ac.uk in the
      directory/pub/software/dos.

PMID- 9183538
TI  - A new index to find regions showing an unexpected variability or conservation in
      sequence alignments.
AB  - Present-day sequences are the result of long and complex pathways of evolution.
      Many of the features encoded in them are the result of a series of evolutionary
      processes, including selection, genetic drift, etc. Following this, protein
      families have a great amount of unexplored information that can be useful for
      many purposes beyond simple evolutionary studies. An index is presented here
      which permits the localization of regions showing an unexpected degree of
      variability or conservation. This index uses the information contained in
      sequence alignments and compares the observed over expected level of variability
      using tables for the relative likelihood of amino acid change.

PMID- 9183539
TI  - A graphical interface for correlated mutations and other protein structure
      prediction methods.

PMID- 9183541
TI  - Genetics and molecular biology.

PMID- 9183540
TI  - Software tool for gene mapping: gRanch.

PMID- 9183542
TI  - Molecular mechanisms of intracellular cholesterol transport.
AB  - Several examples in recent literature show that the molecular principles
      governing intracellular cholesterol transport are starting to emerge. Two
      previously cloned proteins were discovered to play a role in sterol transport of
      steroidogenic cells: the scavenger receptor BI as an HDL receptor and
      steroidogenic acute regulatory protein in the transport of cholesterol to
      mitochondria. Increasing evidence suggests the involvement of multidrug
      resistance proteins in sterol trafficking from the cell surface to the
      endoplasmic reticulum or across the plasma membrane. Specialized plasma membrane
      invaginations, caveolae, were implicated in cholesterol efflux, and the abundant
      caveolar protein, caveolin-1 which belongs to a newly discovered caveolin family
      of proteins, was shown to be a cholesterol-binding membrane protein.

PMID- 9183544
TI  - Vascular gene transfer.
AB  - Vascular gene transfer may be useful for the treatment of several cardiovascular
      diseases. It can also be used as an experimental tool to test the effects of
      various genes in a local vascular compartment. Promising therapeutic effects have
      been obtained in animal models of restenosis with the transfer of vascular
      endothelial growth factor, nitric oxide synthase, thymidine kinase,
      retinoblastoma, growth arrest homeobox gene, cyclin/cyclin-dependent kinase
      inhibitor (p21), and hirudin genes, and antisense oligonucleotides against
      transcription factors or cell cycle regulatory proteins. Vascular endothelial
      growth factor and fibroblast growth factor gene transfers have improved blood
      flow and capillary development in models of ischaemic limb and myocardium. First
      experiences of vascular endothelial growth factor gene transfer to human
      peripheral arteries have also been reported. However, further developments in
      gene delivery techniques and gene transfer vectors will be required before a full
      therapeutic potential of gene therapy in cardiovascular diseases can be
      evaluated.

PMID- 9183543
TI  - Chinese hamster ovary cell mutants affecting cholesterol metabolism.
AB  - The approach of somatic cell and molecular genetics for the study of
      intracellular regulation of cholesterol metabolism has blossomed in recent years.
      This review lists all the Chinese hamster ovary cell mutants involved in
      cholesterol metabolism. In addition, it summarizes the characteristics of mutants
      involved in three different processes: (1) sequential cleavage of the membrane
      bound sterol regulatory element-binding proteins; (2) cholesterol esterification;
      and (3) intracellular cholesterol transport from the lysosome/endosome.

PMID- 9183545
TI  - The tissue-specific expression of lipoprotein lipase: implications for energy and
      lipoprotein metabolism.
AB  - The dual function of lipoprotein lipase as a triglyceride hydrolase and a
      ligand/bridging factor for receptor-mediated lipoprotein uptake implies an
      important role of the enzyme in the distribution of fatty acids and lipoproteins
      among extrahepatic tissues. Observations in humans and, more recently, in several
      induced mutant mouse strains have provided important insights on how fat calories
      and lipids are partitioned to storage or energy production through the tissue
      specific regulation of lipoprotein lipase in adipose tissue and muscle.
      Imbalances of the tissue-specific expression of lipoprotein lipase were
      recognized as potentially important effectors of lipoprotein metabolism, energy
      homeostasis and body weight regulation.

PMID- 9183546
TI  - Is familial combined hyperlipidaemia a genetic disorder of adipose tissue?
AB  - Familial combined hyperlipidaemia is a common cause of coronary heart disease.
      Its aetiology is heterogeneous. The genetic and metabolic basis of the disorder
      has not yet been defined. This review discusses the putative role of adipose
      tissue in the pathogenesis of familial combined hyperlipidaemia. It is possible
      that mutations in genes regulating the turnover of lipids in fat cells are
      involved in the aetiology.

PMID- 9183547
TI  - How to tackle genetic loci predisposing to atherosclerosis?
AB  - To identify major genes influencing the complex disease process of
      atherosclerosis, the strategy for collection of study materials should be
      designed with care to enrich the genetic factors. The tools for an efficient gene
      search are provided by the Human Genome Program; current genetic maps with dense
      marker sets provide a basis for genome-wide scans, and close to complete physical
      maps and identification of coding regions of all human genes within next few
      years offer the scaffolding for the final recognition of genes predisposing to
      atherosclerosis. The statistical methods applicable in the initial gene search of
      complex diseases have developed during recent years including now exact
      modifications of association analysis, also advanced multipoint analyses
      applicable in both parametric (linkage analysis) and nonparametric (affected sib
      pair) methods and maximizing the information extractable from individual
      genotypes. Genome scans in the relevant animal models will often guide to
      important genomic regions, and genetically modified animals will be of essential
      importance for final understanding of the molecular pathogenesis of
      atherosclerosis.

PMID- 9183548
TI  - Molecular genetics of plasma cholesteryl ester transfer protein.
AB  - Plasma cholesteryl ester transfer protein facilitates the transfer of cholesteryl
      ester from HDL to apolipoprotein B-containing lipoproteins, and is a key protein
      in the reverse cholesterol transport system. The importance of plasma cholesteryl
      ester transfer protein in lipoprotein metabolism was highlighted by the discovery
      of deficient individuals with a marked hyper-HDL-cholesterolemia. Cholesteryl
      ester transfer protein deficiency causes various abnormalities in the
      concentration, composition, and functions of both HDL and LDL. Its significance
      in atherosclerosis is still controversial. However, in-vitro evidence shows large
      cholesteryl ester-rich HDL particles in cholesteryl ester transfer protein
      deficiency are defective in cholesterol efflux. Recent epidemiological studies
      have demonstrated an increased incidence of coronary atherosclerosis in deficient
      patients. The current review will also focus on the molecular genetics of the
      protein.

PMID- 9183549
TI  - The role of 15-lipoxygenase in atherogenesis: pro- and antiatherogenic actions.
AB  - Oxidative modification converts LDL to an atherogenic form and 15-lipoxygenase
      has been implicated in this process. Several lines of experimental evidence
      support such a proatherogenic action of the enzyme. However, recent data obtained
      with transgenic rabbits overexpressing 15-lipoxygenase suggest also an
      antiatherogenic effect. In this paper the pathophysiological relevance of 15
      lipoxygenase in atherogenesis is critically reviewed.

PMID- 9183551
TI  - Genetics and molecular biology.

PMID- 9183550
TI  - Molecular genetics of the fibrinolytic and coagulation systems in haemostasis,
      thrombogenesis, restenosis and atherosclerosis.
AB  - The plasminogen and coagulation systems have been extensively characterized at
      the biochemical level. Recent gene targeting and gene transfer studies have
      provided novel insights into their role in the formation of blood vessels and in
      the pathogenesis of blood vessel disorders including thrombosis, restenosis and
      atherosclerosis.

PMID- 9183553
TI  - Genetics and molecular biology.

PMID- 9183554
TI  - Lipid metabolism.

PMID- 9183552
TI  - Nutrition and therapeutics.

PMID- 9183555
TI  - Hyperlipidemia and cardiovascular disease.

PMID- 9183556
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 9183557
TI  - Therapy and clinical trials: ancillary effects of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors.

PMID- 9183558
TI  - Induction of coagulation effects by Wyeth-14,643 in Crl:CD BR rats.
AB  - A two-year mechanistic bioassay in male Crl:CD BR rats was initiated with 50 ppm
      Wyeth-14,643 (WY) to investigate the relationship between peroxisome
      proliferating compounds and Leydig cell adenoma formation. After 154 days, the
      survival rate in the WY group decreased below control levels. After 300 days, the
      dose was lowered to 25 ppm for the remainder of the study. Gross examination of
      WY-treated rats either found dead or euthanized in extremis revealed hemorrhages
      at several sites. To investigate this observation, blood was then collected on
      test day 281 from 10 randomly selected control and WY-treated rats and a clinical
      pathological examination was performed. The WY-treated rats had significantly
      decreased red blood cell count, hemoglobin, and hematocrit, and elevated platelet
      counts. In the WY-treated rats, prothrombin times in undiluted plasma were
      similar to the controls, but were markedly prolonged in 2 of 10 rats when the
      plasma samples were diluted to 25%. Subsequently, blood was collected prior to
      sacrificing WY-treated rats which were exhibiting clinical signs of anemia. These
      rats had prolonged prothrombin times, activated partial thromboplastin time, and
      thrombin clot time when compared to laboratory historical control data (116.7 vs
      13.3, 116.4 vs 13.7, and 42.4 vs 25.7 seconds, respectively). In a subsequent,
      ongoing study, Vitamin K was added to control and WY-treated diets (100 ppm). No
      survival differences between control and WY-treated rats occurred through 260
      days in this second study. These new data suggest that deaths in the WY-treated
      group in our initial study were due to a vitamin K deficiency. The role of
      increased serum estradiol, its effects on blood coagulation, and enhanced hepatic
      cell proliferation in the vitamin K-dependent coagulation processes warrant
      further investigation.

PMID- 9183559
TI  - Purification and characterization of dexamethasone inducible hepatic cytochrome
      P450 isozymes from rhesus monkey.
AB  - Two isozymes of hepatic cytochrome P450 named DEX M-1 and M-2 have been purified
      and characterized from dexamethasone (DEX) pretreated (150 mg Kg-1 body wt x 4
      days) rhesus monkeys by various chromatographic procedures. These isozymes
      demonstrated similar peptide maps. Their absolute and CO-dithionite reduced
      difference spectra demonstrated maximum absorbance at 417 and 449.4 nm,
      respectively. DEX M-1 and M-2 demonstrated polypeptide molecular wt of 50 and
      52.5 KDa, specific content of 16.35 and 11.39 nmol mg-1 protein and 11 and 8 fold
      purification, respectively. The antibodies against these isozymes cross reacted
      with each other and also demonstrated slight differences in the immunoinhibition
      of erythromycin N-demethylase. These results demonstrated that DEX induced two
      different isozymes of hepatic cytochrome P450 in rhesus monkeys.

PMID- 9183560
TI  - In vitro metal inhibition of N-methyl-D-aspartate specific glutamate receptor
      binding in neonatal and adult rat brain.
AB  - The in vitro effect of methyl mercury (MM) and lead (Pb) on N-methyl-D-aspartate
      (NMDA)-specific glutamate receptor binding in neonatal (10 days old) and adult
      rat brain was investigated. The cerebral cortex was isolated from the neonatal
      and adult male Sprague-Dawley rats and the synaptic plasma membranes were
      prepared to study the NMDA-specific glutamate receptor binding by using (3H)
      glutamic acid. The metal salts such as methyl mercury chloride and lead acetate
      were used to study the effect of MM and Pb. Both MM and Pb significantly
      inhibited the receptor binding in neonatal and adult rat brain in a concentration
      dependent manner. MM (IC50:0.95 +/- 0.08 microM) was more potent in inhibiting
      the receptor binding than Pb (IC50:60 +/- 7 microM) in neonatal rat brain. A
      similar high potency was observed for MM than Pb in adult rat brain but the IC50
      values are very high (70 +/- 6 microM and 300 +/- 24 microM respectively)
      indicating less effect compared to neonatal brain. The data suggest that NMDA
      receptor binding was more sensitive to MM and Pb in neonatal brain than in adult.
      MM was more effective than Pb because of its more lipophilicity.

PMID- 9183561
TI  - Acute toxicity of stevioside, a natural sweetener, and its metabolite, steviol,
      in several animal species.
AB  - The acute toxicity of stevioside and steviol (a product of enzymatic hydrolysis
      of stevioside) was investigated in three animal species including rat, mouse and
      hamster. The susceptibility to stevioside and steviol acute toxicity in both
      sexes of these animal species was compared. The animals were treated
      intragastrically with stevioside or steviol and general signs and symptoms were
      observed. The numbers of dead animals were recorded within a period of 14 days
      after administration for estimation of LD50. Stevioside at a dose as high as 15
      g/kg BW was not lethal to either mice, rats or hamsters. Hamsters were found to
      be more susceptible to steviol than rats or mice. LD50 values of steviol in
      hamsters were 5.20 and 6.10 g/kg BW for males and females, respectively. In rats
      and mice, LD50 values of steviol were higher than 15 g/kg BW in both sexes.
      Histopathological examination in the kidney of hamsters induced by steviol
      revealed severe degeneration of the proximal tubular cells. These structural
      alterations were correlated with the increases in serum blood urea nitrogen (BUN)
      and creatinine. Therefore, the possible cause of death induced by steviol might
      be due to acute renal failure.

PMID- 9183562
TI  - Evaluation of the developmental toxicity of benzo[a]pyrene and 2
      acetylaminofluorene using Xenopus: modes of biotransformation. Stover Group.
AB  - The developmental toxicities of benzo[a]pyrene (BAP) and 2-acetylaminofluorene
      (AAF) were evaluated using FETAX (Frog Embryo Teratogenesis Assay-Xenopus). Young
      X. laevis embryos were exposed to these two compounds in each of two separate
      concentration-response experiments with and without an exogenous metabolic
      activation system (MAS) and/or inhibited MAS. The MAS was treated with cimetidine
      (CIM), ellipticine (ELL), or alpha-napthoflavone (alpha-N) to selectively
      modulate cytochrome P-450 activity. Bioactivation of both of these compounds was
      indicated by increased developmental toxicity observed in MAS tests. Results
      obtained in treated MAS tests indicated that BAP was predominantly activated by
      Cytochrome P-450 isozyme CYP1A1. AAF bioactivation was shown to be only partly
      mediated by CYP1A1/2. Detoxification pathways for these two compounds were
      investigated by treatment of the MAS with cyclohexene oxide (CHO) and diethyl
      maleate (DM) to inhibit the epoxide hydroxylase and glutathione conjugation
      pathways, respectively. Results indicated that epoxide hydroxylase was primarily
      responsible for the detoxification of BAP, with glutathione conjugation playing a
      secondary role. Detoxification of AAF by these two pathways was not indicated.

PMID- 9183563
TI  - Repeated dose toxicity study (28 days) in rats and mice with N-methylpyrrolidone
      (NMP).
AB  - Twenty-eight day feeding studies were conducted to evaluate the repeated dose
      toxicity of NMP, a widely used industrial solvent, in Crl:CD BR rats and B6C3F1
      mice. Groups of 5 male and 5 female rats each were fed either 0, 2,000, 6,000,
      18,000, or 30,000 ppm NMP; similar groups of mice were fed either 0, 500, 2,500,
      7,500, or 10,000 ppm. In vivo parameters, hematology and clinical chemistry
      parameters, and complete pathology evaluations were conducted after approximately
      28 days. Decrements in mean body weight gains, reflecting decreases in food
      consumption and efficiency, were seen in male rats fed 18,000 ppm and in both
      sexes fed 30,000 ppm. In rats, clinical chemical changes, indicating possible
      compound-related alterations in lipid, protein, and carbohydrate metabolism,
      occurred at 18,000 ppm in males and 30,000 ppm in both sexes. No
      histopathological changes in rats were judged to be directly related to NMP
      exposure. Hematological (mild to moderate leukopenia) and histopathological
      alterations (hypocellular bone marrow, testicular degeneration and atrophy, and
      thymic atrophy) were judged to be secondary to nutritional and body weight
      effects in male and/or female rats at 30,000 ppm. In mice, cloudy swelling of the
      epithelia of the distal parts of the renal tubuli was observed in 4 males and 3
      females at 10,000 ppm and in 2 male mice at 7,500 ppm. For both rats and mice,
      abnormal urine coloration was observed (in mice at 2,500 ppm and above, and in
      rats at 18,000 ppm and above). The discoloration was interpreted as a sign of
      systemic availability of the test substance, but not as an adverse effect. The
      NOAEL was 6,000 ppm for male rats and 18,000 ppm for female rats. In mice, the
      NOAEL was 2,500 ppm based on the kidney histopathology.

PMID- 9183564
TI  - Inhibition of lipid peroxidation by selenium in chick embryos.
AB  - Toxic doses of Selenium (Se) (12.5 and 37.5 micro moles/Kg egg wt.) administered
      to 14 day old chick embryos reduced the level of lipid peroxides (LPO)
      significantly both in hepatic and brain tissues. However, the LPO formation was
      inhibited maximally at early hours after exposure (3 h and 6 h) and it was
      gradually increased thereafter to normal levels by 48 h. Further, the effect of
      Se on some of the antioxidant enzymes like glutathione peroxidase (GPx),
      glutathione transferase (GST), glutathione reductase (GR), superoxide dismutase
      (SOD) and catalase were studied. In hepatic tissues GPx, GST and SOD activities
      were increased at 6 h post treatment with no change in the activities of GR and
      catalase. However, at 48 h GST and catalase activities were found to be
      increased, while GPx, GR and SOD activities were not affected. In brain at 6 h
      increase in the activities of GPx, GST, GR and SOD and no change of catalase were
      observed. At 6 h glutathione (GSH) levels were reduced in both hepatic and brain
      tissues. Our results suggest that the elevated levels of antioxidant enzymes at
      early hours were successful in bringing LPO levels back to normal.

PMID- 9183565
TI  - Developmental toxicity of dimethyl sulfate by inhalation in the rat.
AB  - Dimethyl sulfate (DMS; CAS No. 77-78) is a colorless, oily liquid which is used
      as a chemical intermediate and as a reactant in producing polyurethane resins. In
      this study, groups of pregnant Crl:CD BR rats were exposed, nose-only, to either
      0.1, 0.7 or 1.5 ppm DMS by inhalation for 6 hr/day from Days 7 through 16 of
      gestation (day in which copulation plug was detected was designated Day 1G). A
      control group of pregnant rats was exposed simultaneously to air only. All female
      rats were euthanized on Day 22G and the fetuses were examined. A suppression of
      both food consumption and the rate of body weight gain was seen in the 0.7 and
      1.5 ppm groups. No unusual clinical signs were seen in rats exposed to DMS. None
      of the reproductive parameters was altered in any of the groups and no
      statistically significant fetal effects were detected. DMS is not a developmental
      toxin in the rat following inhalation exposures up to 1.5 ppm during the period
      of major organogenesis.

PMID- 9183566
TI  - Molecular endocrinology of hydroxysteroid dehydrogenases.

PMID- 9183567
TI  - Steroid receptor interactions with heat shock protein and immunophilin
      chaperones.
AB  - We have provided a historical perspective on a body of steroid receptor research
      dealing with the structure and physiological significance of the untransformed 9S
      receptor that has often confused both novice and expert investigators. The
      frequent controversies and equivocations of earlier studies were due to the fact
      that the native, hormone-free state of these receptors is a large multiprotein
      complex that resisted description for many years because of its unstable and
      dynamic nature. The untransformed 9S state of the steroid and dioxin receptors
      has provided a unique system for studying the function of the ubiquitous,
      abundant, and conserved heat shock protein, hsp90. The hormonal control of
      receptor association with hsp90 provided a method of manipulating the receptor
      heterocomplex in a manner that was physiologically meaningful. For several
      steroid receptors, binding to hsp90 was required for the receptor to be in a
      native hormone-binding state, and for all of the receptors, hormone binding
      promoted dissociation of the receptor from hsp90 and conversion of the receptor
      to the DNA-binding state. Although the complexes between tyrosine kinases and
      hsp90 were discovered earlier, the hormonal regulation or steroid receptor
      association with hsp90 permitted much more rapid and facile study of hsp90
      function. The observations that hsp90 binds to the receptors through their HBDs
      and that these domains can be fused to structurally different proteins bringing
      their function under hormonal control provided a powerful linkage between the
      hormonal regulation of receptor binding to hsp90 and the initial step in steroid
      hormone action. Because the 9S receptor hsp90 heterocomplexes could be physically
      stabilized by molybdate, their protein composition could be readily studied, and
      it became clear that these complexes are multiprotein structures containing a
      number of unique proteins, such as FKBP51, FKBP52, CyP-40, and p23, that were
      discovered because of their presence in these structures. Further analysis showed
      that hsp90 itself exists in a variety of native multiprotein heterocomplexes
      independent of steroid receptors and other 'substrate' proteins. Cell-free
      systems can now be used to study the formation of receptor heterocomplexes. As we
      outlined in the scheme of Fig. 1, the multicomponent receptor-hsp90 heterocomplex
      assembly system is being reconstituted, and the importance of individual
      proteins, such as hsp70, p60, and p23, in the assembly process is becoming
      recognized. It should be noted that our understanding of the mechanism and
      purpose of steroid receptor heterocomplex assembly is still at an early stage. We
      can now speculate on the roles of receptor-associated proteins in receptor
      action, both as individuals and as a group, but their actual functions are still
      vague or unknown. We can make realistic models about the chaperoning and
      trafficking of steroid receptors, but we don't yet know how these processes
      occur, we don't know where chaperoning occurs in the cell (e.g. Is it limited to
      the cytoplasm? Is it a diffuse process or does chaperoning occur in association
      with structural elements?), and, with the exception of the requirement for
      hormone binding, we don't know the extent to which the hsp90-based chaperone
      system impacts on steroid hormone action. It is not yet clear how far the
      discovery of this hsp90 heterocomplex assembly system will be extended to the
      development of a general understanding of protein processing in the cell. Because
      this assembly system is apparently present in all eukaryotic cells, it probably
      performs an essential function for many proteins. The bacterial homolog of hsp90
      is not an essential protein, but hsp90 is essential in eukaryotes, and recent
      studies indicate that the development of the cell nucleus from prokaryotic
      progenitors was accompanied by the duplication of genes for hsp90 and hsp70
      (698). (ABSTRACT TRUNCATED)

PMID- 9183568
TI  - Steroidogenic factor 1: a key determinant of endocrine development and function.

PMID- 9183569
TI  - Developmental and functional biology of the primate fetal adrenal cortex.
AB  - The unique characteristics of the primate (particularly human) fetal adrenal were
      first realized in the early 1900s when its morphology was examined in detail and
      compared with that of other species. The unusual architecture of the human fetal
      adrenal cortex, with its unique and disproportionately enlarged fetal zone, its
      compact definitive zone, and its dramatic remodeling soon after birth captured
      the interest of developmental anatomists. Many detailed anatomical studies
      describing the morphology of the developing human fetal adrenal were reported
      between 1920 and 1960, and these morphological descriptions have not changed
      significantly. More recently, it has become clear that fetal adrenal cortical
      growth involves cellular hypertrophy, hyperplasia, apoptosis, and migration and
      is best described by the migration theory, i.e. cells proliferate in the
      periphery, migrate centripetally, differentiate during their migration to form
      the functional cortical zones, and then likely undergo apoptosis in the center of
      the cortex. Consistent with this model, cells of intermediate phenotype, arranged
      in columnar cords typical of migration, have been identified between the
      definitive and fetal zones. This cortical area has been referred to as the
      transitional zone and, based on the expression of steroidogenic enzymes, we
      consider it to be a functionally distinct cortical zone. Elegant experiments
      during the 1950s and 1960s demonstrated the central role of the primate fetal
      adrenal cortex in establishing the estrogenic milieu of pregnancy. Those findings
      were among the first indications of the function and physiological role of the
      human fetal adrenal cortex and led Diczfalusy and co-workers to propose the
      concept of the feto-placental unit, in which DHEA-S produced by the fetal adrenal
      cortex is used by the placenta for estrogen synthesis. Tissue and cell culture
      techniques, together with improved steroid assays, revealed that the fetal zone
      is the primary source of DHEA-S, and that its steroidogenic activity is regulated
      by ACTH. In recent years, function of the human and rhesus monkey fetal adrenal
      cortical zones has been reexamined by assessing the localization and ontogeny of
      steroidogenic enzyme expression. The primate fetal adrenal cortex is composed of
      three functionally distinct zones: 1) the fetal zone, which throughout gestation
      does not express 3 beta HSD but does express P450scc and P450c17 required for
      DHEA-S synthesis; 2) the transitional zone, which early in gestation is
      functionally identical to the fetal zone but late in gestation (after 25-30
      weeks) expresses 3 beta HSD, P450scc, and P450c17, and therefore is the likely
      site of glucocorticoid synthesis, and 3) the definitive zone, which lacks P450c17
      throughout gestation but late in gestation (after 22-24 weeks) expresses 3 beta
      HSD and P450scc, and therefore is the likely site of mineralocorticoid synthesis.
      Indirect evidence, based on effects of P450c21 deficiency and maternal estriol
      concentrations, indicate that the fetal adrenal cortex produces cortisol and DHEA
      S early in gestation (6-12 weeks). However, controversy exists as to whether
      cortisol is produced de novo or derived from the metabolism of progesterone, as
      data regarding the expression of 3 beta HSD in the fetal adrenal cortex early in
      gestation are conflicting. During the 1960s, Liggins and colleagues demonstrated
      that in the sheep, cortisol secreted by the fetal adrenal cortex late in
      gestation regulates maturation of the fetus and initiates the cascade of events
      leading to parturition. Those pioneering discoveries provided insight into the
      mechanism underlying the timing of parturition and therefore were of particular
      interest to obstetricians and perinatologists confronted with the problems of
      preterm labor. However, although cortisol emanating from the fetal adrenal cortex
      promotes fetal maturation in primates as it does in sheep, its role in the
      regulation of primate parturition, unlike that in sheep

PMID- 9183570
TI  - The regulation of thyroid function in pregnancy: pathways of endocrine adaptation
      from physiology to pathology.

PMID- 9183571
TI  - The fetal origins of coronary heart disease.

PMID- 9183572
TI  - Detection of acute rejection: validation of non-invasive diagnostic tests.

PMID- 9183573
TI  - Risk stratification after acute myocardial infarction in the thrombolytic era.

PMID- 9183574
TI  - Blood pressure, ageing and mortality.

PMID- 9183575
TI  - Primary ventricular fibrillation: a reason to be cautious.

PMID- 9183576
TI  - Angina pectoris and the personality factor: the relevance of psychosocial factors
      in myocardial ischaemia.

PMID- 9183577
TI  - Abnormal dynamics of ventricular repolarization--a new insight into the
      mechanisms of life-threatening ventricular arrhythmias.

PMID- 9183578
TI  - Management of myocardial infarction: the proper priorities.

PMID- 9183579
TI  - Should patients with suspected acute myocardial infarction without ST elevation
      be given thrombolytic treatment?

PMID- 9183580
TI  - The Denolin Lecture 1996. Mechanical heart valves. Conclusions from long-term
      follow-up.

PMID- 9183581
TI  - Psychosocial variables in female vs male patients with stable angina pectoris and
      matched healthy controls.
AB  - AIM: This study was set up to evaluate psychosocial risk factors in patients with
      stable angina pectoris, with particular attention to gender differences, as this
      has previously been studied mainly in relation to myocardial infarction in males.
      MATERIAL: Seven hundred and sixty-seven patients (236 women) were studied. They
      were selected from the 809 patients included in the Angina Prognosis Study in
      Stockholm (APSIS), and 50 matched healthy subjects. METHOD: Data were gathered by
      structured psychosocial interviews on inclusion into the APSIS study. RESULTS:
      Patients with stable angina pectoris experienced significantly more stressful
      events, and suffered more frequently from disturbed and psychosomatic symptoms
      than healthy controls. At work they experienced less skill discretion and less
      control. The patients had higher rating scores for hostility and lower levels of
      self-rated overall well-being. With regard to gender differences, women were more
      likely to suffer from the strain of work, psychosomatic symptoms, disturbed sleep
      and stressful events than male patients. Females rated less type A-behaviour and
      hostility than males. CONCLUSIONS: These findings suggest that previously known
      psychosocial risk factors for acute myocardial infarction are more common in
      patients with stable angina pectoris than in controls, and differ between female
      and male patients.

PMID- 9183582
TI  - Does in-hospital ventricular fibrillation affect prognosis after myocardial
      infarction?
AB  - AIM: The aim of this study was to estimate the prognostic information to be
      gained from ventricular fibrillation in patients with myocardial infarction.
      METHODS AND RESULTS: We studied 4259 consecutive patients with myocardial
      infarction admitted to one centre in 1977-1988. Five hundred and twenty-eight
      (12.4%) of the patients had ventricular fibrillation in hospital. The following
      risk factors were included in multivariate models to estimate their importance
      for 30-day and long-term (median 7 year) prognosis: age, gender, ventricular
      fibrillation, congestive heart failure, pulmonary oedema, cardiogenic shock,
      other cardiac arrest and atrial fibrillation. We found that the odds ratio for
      death on days 6.30 was 6.34 (3.55-11.30, 95% confidence limits, P < 0.001) for
      patients with primary ventricular fibrillation (without heart failure) and 4.06
      (2.68-6.14, P < 0.001) for patients with ventricular fibrillation secondary to
      heart failure compared to patients without ventricular fibrillation. For patients
      surviving more than 30 days, relative risk of death in those with ventricular
      fibrillation was 1.11 (95% confidence interval 0.93-1.34, P = 0.26). Logistic
      regression analysis of relative risk associated with ventricular fibrillation in
      time intervals, indicated that the importance of ventricular fibrillation for
      risk of death was exhausted during the initial 60 days after infarction.
      CONCLUSION: Ventricular fibrillation is associated with an independent increased
      risk of death within 0-60 days after infarction. After this period, the prognosis
      in survivors of ventricular fibrillation does not differ significantly from
      patients without ventricular fibrillation.

PMID- 9183583
TI  - Dipyridamole thallium-201 imaging very early after uncomplicated acute myocardial
      infarction in patients treated with thrombolytic therapy.
AB  - The aim of this study was to assess the safety and prognostic value of
      dipyridamole 201T1 imaging very early after acute myocardial infarction in
      patients treated with thrombolytic therapy. Fifty-two consecutive patients with
      an uncomplicated clinical course underwent quantitative planar dipyridamole 201T1
      imaging 2 5 days after acute myocardial infarction. The patients were followed
      for 14 +/- 7 months after discharge. No major complications occurred during the
      test. Of the 30 patients with redistribution, five (16.6%) developed in-hospital
      unstable angina as against none of the 22 patients without redistribution. During
      follow-up, a total of live late cardiac events were observed: two deaths and two
      cases of unstable angina in the group with reversible defects and one
      reinfarction in the group with fixed defects. The 1-year actuarial probability of
      being free of cardiac events was, respectively, 66 +/- 10% and 94 +/- 5% in the
      patients with and without redistribution (P < 0.01). In conclusion, in patients
      treated with thrombolysis, dipyridamole-201T1 imaging very early after
      uncomplicated acute myocardial infarction is a feasible and safe test. Patients
      with fixed defects appear to be at low risk and may be candidates for early
      discharge; the presence of redistribution identifies a subgroup of patients who
      may benefit from further careful clinical evaluation.

PMID- 9183584
TI  - Comparison of usefulness of computer assisted continuous 48-h 3-lead with 12-lead
      ECG ischaemia monitoring for detection and quantitation of ischaemia in patients
      with unstable angina.
AB  - AIMS: The selection of ECG leads used for ST monitoring may influence detection
      and quantitation of ischaemia. METHODS: We compared on-line continuous 48-h 12
      lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI
      100). Onset and offset of ST episodes were defined by the lead with the first >
      or = 100 microV ST change relative to baseline and the lead with the latest
      return to baseline ST level, respectively. ST episodes were calculated for 12
      leads and 3 leads (V2, V5, III) separately. RESULTS: ST episodes were detected in
      88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P
      < 0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead
      and 2 (1.6) for 12-lead (P < 0.0001). The total duration of ischaemia detected
      during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3)
      min respectively (P < 0.0001). The probability of recurrent ischaemia declined
      most during the first 24 h of monitoring. After a period without ST changes of 1,
      12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%,
      respectively. CONCLUSIONS: Continuous 12-lead ST monitoring increases detection
      rate and duration of ST episodes compared to 3-lead ST monitoring. The use of
      continuous 12-lead ECG monitoring devices on emergency wards and coronary care
      units is recommended.

PMID- 9183585
TI  - Prediction of improvement of ventricular function after revascularization. 18F
      fluorodeoxyglucose single-photon emission computed tomography vs low-dose
      dobutamine echocardiography.
AB  - AIMS: To compare assessment of myocardial flow and glucose metabolism by single
      photon emission computed tomography (SPECT) with low-dose dobutamine
      echocardiography in predicting improvement in regional and global left
      ventricular function after coronary artery bypass grafting. METHODS AND RESULTS:
      Thirty patients with regional wall motion abnormalities (mean ejection fraction
      32 +/- 19%) were studied with low-dose dobutamine echocardiography (5 and 10
      micrograms. kg-1 min-1) and thallium-201/ 18F-fluorodeoxyglucose(FDG) SPECT prior
      to surgery. For comparative analysis, a 13-segment model was used. Postoperative
      improvement was predicted if the echocardiogram showed that wall motion
      abnormalities were reversible during the dobutamine infusion and there was normal
      perfusion or relatively increased FDG uptake in perfusion defects (mismatch) in
      dyssynergic segments on SPECT. After surgery, ventricular function was
      reassessed. An echocardiogram was taken at the 3 month follow-up with the patient
      at rest. Regional wall motion had improved in 62/168 (37%) revascularized
      segments. In predicting functional outcome, low-dose dobutamine echocardiography
      reached a sensitivity of 89% and a specificity of 82%, with a positive predictive
      value of 74% and a negative predictive value of 93%, whereas for thallium-201/FDG
      SPECT these values were 84%, 86%, 78% and 90%, respectively. In patients with
      more than two viable segments on either technique, the wall motion score index, a
      surrogate of global ventricular function, improved significantly. CONCLUSION: For
      the optimal prediction of functional outcome, combined assessment of flow and FDG
      imaging is needed. Both thallium-201/FDG SPECT and low-dose dobutamine
      echocardiography appear comparable and similarly accurate in predicting
      improvement of left ventricular function after surgical revascularization.

PMID- 9183586
TI  - Intravascular ultrasonic evidence by constant cross-sectional area of
      atherosclerotic plaques during coronary vasomotion in humans.
AB  - AIMS: This study aims to visualize ultrasonically deformation of atherosclerotic
      plaques in human coronary arteries during vasoconstriction and vasodilatation.
      METHODS AND RESULTS: Intravascular ultrasound detected occult atherosclerosis in
      angiographically normal coronary arteries of eight patients with chest pain at
      rest. During the acetylcholine provocative test, intravascular ultrasound
      monitored deformation of the atherosclerotic plaques. At the last step of the
      test, intracoronary injection of isosorbide dinitrate caused vasodilation. Under
      control, acetylcholine-treated, and isosorbide dinitrate-treated conditions,
      cross-sectional areas of sonolucent circle and vessel lumen were measured.
      Subtraction of the latter from the former gave the area of atherosclerotic
      plaque. In the process of vasoconstriction and vasodilation, the plaque area did
      not change significantly. CONCLUSION: The cross-sectional area of the
      atherosclerotic plaque appeared to be constant during vasomotion of human
      coronary arteries.

PMID- 9183587
TI  - Importance of flow/metabolism studies in predicting late recovery of function
      following reperfusion in patients with acute myocardial infarction.
AB  - AIMS: Positron emission tomographic imaging is known to be a reliable indicator
      of viable myocardium in chronic heart disease. Its value in acute myocardial
      infarction has not been studied extensively. METHODS AND RESULTS: Sixty-two
      patients receiving thrombolytic therapy were studied. Myocardial tissue flow and
      metabolism were measured at 5 days and 3 months. Recovery of left ventricular
      function was investigated with echocardiography or radionuclide ventriculography.
      In eight patients, normal flow was found in the infarct area at 5 days with no
      significant changes in flow, metabolism or function over the next 3 months. In 54
      patients, impaired regional myocardial blood flow in the infarct zone was
      observed at 5 days. In 39 patients, there was a matching positron emission
      tomographic pattern, while in 15 the pattern was mismatched. None of the patients
      with a TIMI flow grade < 3 revealed recovery of left ventricular function. In
      seven out of 11 patients with TIMI 3 flow and a mismatching pattern, additional
      angioplasty was performed with functional improvement in six. CONCLUSIONS:
      Recovery of ventricular function is exclusively found in patients with a TIMI
      flow grade 3. Patients with a positron emission tomographic mismatching pattern
      reveal functional recovery only after subsequent angioplasty.

PMID- 9183588
TI  - A sex difference in short-term survival after initial acute myocardial
      infarction. The MONICA-Bremen Acute Myocardial Infarction Register, 1985-1990.
AB  - AIMS: To assess the difference between men and women as regards fatality shortly
      after acute myocardial infarction, and the relationship of patient
      characteristics. METHODS AND RESULTS: One thousand seven hundred and ten male and
      563 female patients, 25-69 years of age and hospitalized with a first acute
      myocardial infarction occurring from 1985 to 1990, were included in the
      population-based World Health Organization MONICA-Bremen Acute Myocardial
      Infarction Register. Patient information, including short-term survival status,
      was obtained from the medical records of the seven Bremen hospitals with internal
      medicine departments and municipal death certificate files. The unadjusted 28-day
      fatality rate after acute myocardial infarction was higher among women than among
      men (23.1% vs 16.1% respectively: P < 0.001). Adjusting for the older age of
      women did not eliminate the difference completely (females; 20.9%, males: 16.8%;
      P = 0.041). Controlling for previous use of inotropic medicine and diuretics,
      during-the-event receipt of thrombolysis and platelet inhibitors, and age in
      logistic regression analyses resulted in a similar 28-day mortality risk after
      acute myocardial infarction for both sexes (female/male odds ratio = 1.13, 95%
      confidence interval = 0.86 1.50; P = 0.389). CONCLUSIONS: Sex was not an
      independent predictor of early acute myocardial infarction fatality. Our data
      suggest that the excess mortality risk in women can be explained by sex
      differences in age, pre-infarction cardiac impairment, and treatment during the
      coronary event.

PMID- 9183589
TI  - Skeletal muscle alterations in patients with chronic heart failure.
AB  - AIMS: To investigate skeletal muscle in patients with chronic heart failure and
      controls, and relate skeletal muscle variables to functional class, exercise
      capacity, central haemodynamics, muscle strength and medical treatment. METHODS:
      Biopsy from the lateral vastus muscle was obtained in 43 patients and 20
      controls. Right sided heart catheterization was performed in 19 patients and
      maximal exercise testing in 26 patients. In nine patients muscle strength was
      measured. Patients had higher lactate levels, higher lactate dehydrogenase
      activity, and lower oxidative enzymes activity than controls. In patients, the
      percentage of type I fibres and capillarization were decreased while the
      percentage of type II B fibres were increased. Lactate dehydrogenase activity
      correlated with exercise capacity, muscle strength and right atrial pressure.
      Digoxin-treated patients had significantly lower oxidative enzyme activity than
      patients without digoxin treatment. CONCLUSION: Patients with chronic heart
      failure have several skeletal muscle abnormalities. Central haemodynamics and
      medical treatment may, in addition to inactivity, be important in skeletal muscle
      changes.

PMID- 9183590
TI  - The prevalence of left ventricular diastolic filling abnormalities in patients
      with suspected heart failure.
AB  - AIMS: It is reported that one third of patients with heart failure have normal
      left ventricular systolic function, and may or may not have left ventricular
      diastolic dysfunction. We sought to define the prevalence of left ventricular
      diastolic filling abnormalities in a large unselected group of patients, unlike
      the diagnosis by exclusion in the small highly selected groups of patients
      studied previously. METHODS AND RESULTS: Patients were referred by general
      practitioners to an open-access echocardiography service for assessment of
      possible heart failure. Echocardiography included a Doppler study of transmitral
      flow at the tips of the mitral leaflets and calculation of an E/A ratio. Of 534
      patients referred and assessed, 371 patients had normal systolic function and a
      measurable E/A ratio. These were compared with age-adjusted reference ranges to
      give 9 above the reference range and 19 below. This is only 10 more than would be
      expected if our patients were normal. In the same group of patients we found 96
      cases of left ventricular systolic dysfunction, or 52 amongst the 423 with a
      measurable E/A ratio. CONCLUSION: Either left ventricular diastolic filling
      abnormalities are very much less common than previously supposed or the E/A ratio
      is almost useless for their detection.

PMID- 9183591
TI  - Multiple mechanisms of successful slow-pathway catheter ablation of common
      atrioventricular nodal re-entrant tachycardia.
AB  - BACKGROUND: In patients with atrioventricular nodal re-entrant tachycardia,
      modifications of the antegrade atrioventricular nodal function curve caused by
      catheter ablation of the so-called slow pathway are heterogeneous, but have not
      yet been systematically evaluated. AIM: To test the hypothesis that successful
      treatment is independent of specific electrophysiological modifications of
      atrioventricular nodal conducting properties. METHOD: Standard
      electrophysiological parameters and comparable antegrade atrioventricular nodal
      function curves were obtained, before and after successful ablation, in 104
      patients (mean age 52 +/- 16 years: 69 women) affected by the common form of
      atrioventricular nodal re-entrant tachycardia. RESULTS: Three different major
      patterns of antegrade atrioventricular nodal function curve were caused by
      ablation: downward shift of the curve with disappearance of atrioventricular
      nodal duality, suggesting the elimination of the slow pathway in 54 (52%)
      patients (type 1): absence of clear modifications of the curve (and of slow
      pathway ablation) in 33 (32%) patients (type 2); upward shift of the curve,
      suggesting a further slowing of conduction velocity through the slow pathway in
      17 (16%) patients (type 3). Type-1 pattern was more frequent in patients < or =
      45 years, whereas type-2 pattern was more frequent in those > 45 years.
      CONCLUSION: Successful ablation of atrioventricular nodal re-entrant tachycardia
      is independent of specific modifications of antegrade atrioventricular conduction
      and probably depends on critical nodal and perinodal tissue damage at different
      sites on the re-entrant circuit. The effects of ablation are influenced by
      patient age.

PMID- 9183592
TI  - Changes in the QT interval and its adaptation to rate, assessed with continuous
      electrocardiographic recordings in patients with ventricular fibrillation, as
      compared to normal individuals without arrhythmias.
AB  - Various QT interval variables and heart rate variability parameters were studied
      in six patients with ventricular fibrillation but without heart disease and
      compared with findings in 21 normal persons. QT and QT dispersion (QTd) were
      measured from conventional 12 lead ECGs: for dynamic QT analysis, QT intervals
      were automatically measured to the end of the T wave (QTe) on a 24 h ECG
      recording. The adaptation of the QT interval to changes in heart rate was
      expressed as the slope of the linear regression lines relating QTc to the RR
      interval (Sc). The complete 24 h ECG recording and four 6 h segments were studied
      (morning, day, evening, and night). Ventricular fibrillation patients had
      slightly prolonged QTmax intervals on the 12 lead ECG, QT dispersion was longer
      in ventricular fibrillation patients than in normal persons (88 +/- 29 ms vs 59
      +/- 26 ms. P < 0.05), and on the 24 h ECG recording, normal persons and
      ventricular fibrillation patients had a comparable RR. In addition, parameters
      for long-term (SD, standard deviation of normal RR intervals) and short-term
      (RMSSD, the root-mean-square successive differences of normal RR intervals heart
      rate variability were not different. Automatic measurement of the QT interval and
      the QTc/RR slopes was possible over 24 h and in the 6 h intervals in a large
      majority of patients (25/27 and 88/108 readings). The mean 24 h QT and the mean 6
      h QT interval were comparable in normal subjects and ventricular fibrillation
      patients except for the day segment. The 24 h Se was significantly lower in
      ventricular fibrillation patients, compared to normal individuals. Furthermore,
      Se in the morning and night segment was also significantly lower in ventricular
      fibrillation patients (both P < 0.05). In conclusion, patients with ventricular
      fibrillation but without underlying structural heart disease have normal heart
      rate variability parameters. However, abnormal repolarization behaviour,
      characterized by an increased QTd and a depressed adaptation of QT to variations
      in RR (especially during the night and the morning), is present. These findings
      may help to understand and treat arrhythmias in this patient group.

PMID- 9183593
TI  - Gender and the relationship between ventricular repolarization and cardiac cycle
      length during 24-h Holter recordings.
AB  - AIMS: There are gender-related differences in the QT interval measured from
      standard ECG tracings. However, these observations are based on a limited number
      of beats recorded in resting conditions. Computerized Holter techniques enable
      ventricular repolarization and its relationship with cardiac cycle length to be
      analysed long term. Previous studies used only the initial portion of the QT
      interval to the T wave apex (QTa) to measure ventricular repolarization; however,
      QTa may underestimate the total QT duration (QTe). The aims of this study were to
      verify whether QTa and QTe had similar rate-dependence in normal subjects and
      whether gender-related QTe differences observed in the resting ECG were also
      present in the long-term QT intervalcycle length relationship. METHODS AND
      RESULTS: Twenty-four hour Holter recordings were obtained in 40 healthy young
      subjects. 20 females and 20 males (mean age 28 +/- 9 and 26 +/- 5 years,
      respectively ns). Two-channel ECG digitized signals were processed using new
      automatic QT analysis software (Ela Medical), which converted the 24-h recordings
      into 2880 30-s templates. It also measured the QT apex (QTa) QT end (QTe) and the
      RR interval (ms) of each template, and computed the slopes of the linear
      regressions of QTe and QTa values plotted against the corresponding RR interval
      (QTe/RR and QTa/RR). Females had a shorter RR interval than males (803 +/- 129 vs
      877 +/- 86 ms. P = 0.037), with longer mean QTc (420 +/- 17 vs 400 +/- 200 ms. P
      = 0.0005). In both genders. QTa/RR slopes were steeper than QTe/RR slopes (P =
      0.0001). Both QTa/RR and QTe/RR slopes were steeper in females than in males
      (QTa/RR 0.20 +/- 0.04 vs 0.16 +/- 0.03, P = 0.001; QTe/RR 0.16 +/- 0.04 vs 0.13
      +/- 0.03, P = 0.027). Of note, QTa and QTe at fixed long cycle lengths (1000 ms)
      were longer in women than in men (QTa1000 330 +/- 20 vs 309 +/- 18 ms: P = 0.002;
      QTe1000 410 +/- 17 vs 389 +/- 19 ms: P = 0.002), while they did not differ at
      fixed short cycle lengths (600 ms). CONCLUSIONS: This study demonstrates that
      both the initial portion of the QT interval (QTa) and the entire QT interval
      (QTe) are useful since QTa is more prolonged than QTe at increasing cycle
      lengths, and thus includes most of the heart rate dependency of ventricular
      repolarization. In normal subjects, both the QTc and the long-term relationship
      between ventricular repolarization and heart rate are affected by gender. The
      differences in QTa and QTe duration between males and females are more marked at
      long cycle lengths and disappear at short cycle lengths. Finally, this study also
      proves the clinical feasibility of assessing the long-term relationship between
      ventricular repolarization and heart rate by utilizing the automatic measurement
      of the QT interval from 24-h Holter recordings.

PMID- 9183594
TI  - Use of troponin-T concentration and kinase isoforms for quantitation of
      myocardial injury induced by radiofrequency catheter ablation.
AB  - BACKGROUND: Although there remains particular concern about late malignant
      ventricular arrhythmias arising from myocardial damage induced by catheter
      ablation, the extent of myocardial injury resulting from clinical ablation
      procedures has not been fully studied. We conducted a prospective, controlled
      study to investigate the use of two newer markers of myocardial integrity,
      troponin-T concentration and creatine kinase isoforms, and a traditional marker,
      creatine kinase-MB concentration, in the assessment of myocardial injury
      following radiofrequency catheter ablation. METHODS AND RESULTS: The study
      population consisted of 28 consecutive patients subjected to radiofrequency
      catheter ablation, and the control group comprised eight subjects undergoing
      diagnostic electrophysiology study. Prior to ablation and at 30 min, 1, 2, 6, and
      12 h following the procedure, blood samples were taken to measure troponin-T and
      creatine kinase-MB concentrations, and the separation of creatine kinase isoforms
      (MM3/MM1 and MB2/MB1 ratios). The troponin-T concentration was above normal in
      all but two patients following radiofrequency ablation, and the MB2/MB1 ratio was
      raised in all but one patient following ablation, but was also abnormal in the
      pre-ablation samples in seven patients. The MM3/MM1 ratio failed to detect
      myocardial injury in 75% of patients. Of patients subjected to ablation, in only
      36% was the creatine kinase-MB concentration raised at least once post-ablation.
      Thirty minutes post-ablation, there was a statistically significant difference
      between the control and patient groups only as regards troponin-T concentration.
      There was a significant association between troponin-T concentration immediately
      post-procedure, the number of discharges delivered (r = 0.52, P = 0.006) and
      maximum power used (r = 0.48, P = 0.009). CONCLUSION: Our results indicate that
      catheter ablation inflicts a cumulative, detectable injury upon the myocardium.
      This injury can be quantitated by using newer analytical techniques, such as
      serial, post-ablation measurements of troponin-T concentration.

PMID- 9183595
TI  - Transcatheter closure of patent ductus arteriosus with the Rashkind occluder.
      Acute results and angiographic follow-up in adults.
AB  - We performed catheter closure of a patent ductus arteriosus with a Rashkind
      occluder in 51 adult patients (aged 14 to 76 years). The diameter of the ductus
      ranged from 2 to 13 mm (mean 4.5 +/- 2.0 mm), QP:QS from 1.0 to 2.6 (mean 1.6 +/-
      0.3). The procedure was successful in 50/51 patients, in one of them at a second
      attempt. In one patient, the ductus could not be closed even with additional
      occluders. This patient was sent for surgery. In two patients with a large
      ductus, two Rashkind umbrellas were implanted simultaneously. Immediately after
      ductus closure, there was a residual shunt in 40/50 patients decreasing to 26/50
      after 20 min. Two of the patients with a residual shunt suffered from haemolysis.
      In 16 patients, the residual shunt disappeared spontaneously within some months.
      In 15 patients, additional occluders (a second occluder in 12, a third occluder
      in one, and a fourth and fifth occluder in another) were implanted during the
      initial procedure or during follow-up. All patients were followed until
      angiography proved complete closure of the ductus. At the time of the last follow
      up angiogram, the ductus was occluded in 49/50 patients; one patient refused a
      follow-up angiogram. Ductus occlusion with the Rashkind umbrella can be
      considered a technique with a high success rate and low rate of complications in
      adults. However, a residual shunt is not uncommon. Additional occluders have to
      be implanted in many patients.

PMID- 9183596
TI  - Blood pressure and mortality in an older population. A 5-year follow-up of the
      Helsinki Ageing Study.
AB  - OBJECTIVE: Hypertension is an established risk factor of cardiovascular diseases,
      and in clinical studies its treatment has reduced cardiovascular complications in
      subjects up to 80 years of age. In the older age groups, prognostic data on blood
      pressure is sparse. We evaluated the prognostic significance of different blood
      pressure levels and the history of elevated blood pressure in an older
      population. DESIGN: In the Helsinki Ageing Study random individuals 75, 80, and
      85 years of age (n = 521) were evaluated at baseline using postal questionnaires,
      structured interviews, clinical examinations, laboratory investigations, and
      blood pressure measurements (supine, seated, standing). Date of death during a 5
      year follow-up was verified using computerized registers, and thus the follow-up
      was 100% complete. The data were analysed using life-table analyses and Cox
      proportional hazards models. RESULTS: At 5 years, 240 subjects (40%) had died,
      50% of them of cardiovascular disease. In crude analyses, an inverse relationship
      between both systolic and diastolic blood pressure and mortality was observed in
      all groups combined (P < 0.01), and separately in the 80 and 85-year-old groups.
      However, a J-shaped link between diastolic blood pressure and mortality was found
      in the 75-year-old group. After controlling for age, gender and the presence of
      clinically significant diseases (in 72% of subjects) baseline blood pressure was
      associated with favourable 5-year survival. The risk ratios of systolic (per 10
      mmHg) and diastolic blood pressure (per 5 mmHg) were 0.90 (95% CI 0.85-0.96) and
      0.92 (95% CI 0.86-0.99), respectively. Neither isolated systolic hypertension nor
      a history of hypertension treatment were associated with 5-year survival.
      CONCLUSION: At the population level, among subjects aged 75 years and over,
      favourable 5-year survival is indicated by a high, but not a low, blood pressure.

PMID- 9183597
TI  - Evaluation of plasma levels of tumour necrosis factor alpha and interleukin-6 as
      rejection markers in a cohort of 142 heart-grafted patients followed by
      endomyocardial biopsy.
AB  - The rejection reaction after cell or organ transplantation has to be detected as
      early as possible in order to conduct optimal immunosuppressive treatment. Among
      the numerous events leading to rejection, cytokine production, especially of
      tumour necrosis factor alpha, is particularly important. Interleukin-6 and tumour
      necrosis factor alpha were investigated in 142 heart-grafted patients in order to
      define an early peripheral non-invasive marker of an acute rejection that could
      fit well with myocardial biopsy results. Cytokines were immunoenzymatically
      measured in blood specimens collected on the day of the endomyocardial biopsy.
      The values were compared to the grade of heart graft rejection established
      according to pathological criteria. Plasma interleukin-6 and especially tumour
      necrosis factor alpha determined on the day of the rejection diagnosis were
      significantly increased in the patient sample with moderate or severe rejection
      when compared with mean values of interleukin-6 and tumour necrosis factor alpha
      in the patient sample without rejection or with mild rejection (P = 0.04 and
      0.001 respectively). Because high levels of tumour necrosis factor alpha may
      appear before histological signs, this biological marker could be useful in the
      follow-up of heart-grafted patients.

PMID- 9183598
TI  - Successful treatment of coronary artery perforation during angioplasty using
      autologous vein graft-coated stent.
AB  - We report a case of successful treatment of coronary artery perforation and
      cardiac tamponade with an autologous vein graft-coated stent, which were
      developed during percutaneous transluminal coronary angioplasty. The method
      reported here may be an effective alternative to emergency surgery and should be
      considered when coronary artery perforation does not respond to conventional
      prolonged inflation with perfusion catheter.

PMID- 9183599
TI  - A case of effort angina pectoris with total obstruction of the left main coronary
      artery and extracardiac anastomose detected by angiography.

PMID- 9183600
TI  - An ARG403GLN beta-myosin heavy chain gene mutation identified in an Italian
      family with hypertrophic cardiomyopathy; description of clinical features of the
      family members.

PMID- 9183601
TI  - Congenital giant left atrial aneurysm in an infant.

PMID- 9183602
TI  - A case of infective endocarditis complicated with anterior mitral valve leaflet
      abscess.

PMID- 9183603
TI  - Pulmonary hypertension associated with thrombotic thrombocytopaenic purpura in
      AIDS patients.

PMID- 9183604
TI  - Treadmill exercise echocardiography: methodology and clinical role.
AB  - Exercise echocardiography using treadmill exercise and immediate post-exercise
      imaging is an accurate means for detecting and stratifying coronary artery
      disease. It is applicable to patients with chest pain syndromes in whom the
      initial diagnosis is being contemplated and also in follow-up of patients after
      myocardial infarction or interventional procedures. Numerous studies have
      demonstrated that its accuracy is equivalent to that of competing radionuclide
      imaging techniques and that it has particular relevance in patients with non
      diagnostic electrocardiograms. In addition to evaluating patients for the
      presence of coronary artery disease, because of the highly versatile nature of
      the imaging modality utilized (two-dimensional echocardiography), stress
      echocardiography is an excellent tool for evaluating atypical symptoms such as
      dyspnoea and fatigue.

PMID- 9183605
TI  - Dobutamine stress echocardiography.
AB  - Dobutamine is a synthetic catecholamine with predominant beta-stimulation. Its
      half-life is approximately 2 min. The positive chronotropic and inotropic effects
      of dobutamine induce myocardial ischaemia if significant coronary artery
      obstruction is present. Regional ischaemia produces regional wall motion
      abnormalities which can be detected by echocardiography. Most dobutamine stress
      protocols start at an infusion rate of 5 micrograms.kg-1.min-1 and increase to a
      peak dose of 40 or 50 micrograms.kg-1.min-1; to further increase heart rate, a
      bolus injection of 0.25-1.0 mg atropine is added. Test endpoints are the
      detection of new wall motion abnormalities, the occurrence of severe
      complications or achievement of the target heart rate. Viable myocardial regions
      have a positive inotropic reserve, which can be stimulated by dobutamine and
      detected by echocardiography. Indications for the use of dobutamine stress
      echocardiography are to prove stress-inducible myocardial ischaemia and to detect
      myocardial viability. The test should only be performed for the detection of
      stress-induced myocardial ischaemia if patients are unable to undergo exercise
      echocardiography, or if patients fail to reach their required test level in
      exercise echocardiography.

PMID- 9183606
TI  - Dipyridamole stress echocardiography: state of the art 1996. EPIC (Echo Persantin
      International Cooperative) Study Group.
AB  - Dipyridamole stress is the forerunner and prototype of pharmacological stress
      echo tests in the diagnosis of coronary artery disease. Among the various stress
      echo tests, it is probably the least technically demanding to perform and the
      easiest to interpret. Its accuracy is similar to dobutamine stress
      echocardiography but its feasibility is higher. The prognostic impact of
      dipyridamole stress echo has also been proven for presentation of hard end-points
      such as cardiac death. The safety and prognostic value of this test has been
      conclusively demonstrated as a result of extensive experience in large scale
      multicentre projects. Dipyridamole stress is many different tests in one:
      dipyridamole atropine is best for diagnosis; dipyridamole dobutamine or
      dipyridamole-exercise is highly sensitive for the detection of minor forms of
      coronary artery disease; low and high dose dipyridamole is best suited for
      prognostic stratification; infra-low dipyridamole with low dose dobutamine
      administration is probably best suited for selective myocardial viability
      identification. Each patient should have their own test, tailored on the basis of
      the clinical picture and the diagnostic issue.

PMID- 9183608
TI  - Adenosine echocardiography in the diagnosis of coronary artery disease.
AB  - Adenosine is a naturally occurring vasodilator which has been used for the
      induction of maximal coronary hyperaemia in the cardiac catheterization
      laboratory and in conjunction with myocardial perfusion scintigraphy. Its use as
      a stress agent with echocardiography is dependent upon the development of
      coronary steal. The sensitivity of adenosine stress echocardiography has been
      reported to be quite variable, depending on the nature of the population studied.
      However, in individuals without previous myocardial infarction, the test has a
      poor sensitivity, particularly in patients with single vessel coronary disease.
      Moreover, although the agent is safe, troublesome side effects are frequent. The
      combination of lower sensitivity than competing techniques, side effects, and
      cost do not favour the combination of adenosine stress with echocardiography.

PMID- 9183607
TI  - Arbutamine stress echocardiography.
AB  - Arbutamine, a new potent non-selective beta-adrenoceptor agonist with mild alpha
      1-sympathomimetic activity, has been developed specifically for pharmacological
      stress testing. The drug acts like physical exercise, increasing both heart rate
      and myocardial contractility. Sensitivity, specificity and accuracy in detecting
      significant stenotic coronary artery disease are 76%, 96%, and 82%, respectively,
      again similar to those of exercise echocardiography. The drug is delivered by a
      computerized drug delivery and monitoring device (GenESA) which adjusts the
      infusion rate according to the patient's heart rate data feedback. The drug is
      generally well tolerated and has an acceptable safety profile. This article
      describes recent clinical experience with arbutamine and presents preliminary
      results of a multicentre multinational study which evaluates the clinical utility
      and safety of the GenESA system in diagnosing coronary artery disease.

PMID- 9183609
TI  - Transoesophageal stress echocardiography.
AB  - Transoesophageal echocardiography has been performed in conjunction with pacing,
      dobutamine, or dipyridamole stress to detect stress-inducible ischaemia, and has
      proved to be a highly accurate diagnostic tool. Its advantages of improved image
      quality and high diagnostic accuracy have to be weighed against the disadvantages
      of semi-invasiveness and patient discomfort. The existing data on this stress
      echo modality and on special applications (diastolic dysfunction, ischaemic
      mitral regurgitation, hibernating myocardium, peri-operative risk assessment) are
      reviewed.

PMID- 9183610
TI  - Stress echocardiography: personnel and technical equipment.
AB  - In recent years, stress echocardiography has gained broad acceptance as a non
      invasive method for the diagnosis of coronary artery disease. Facing different
      protocols, dosages and instrumentation, official guidelines for the performance,
      standardization and quality control of stress echocardiograms are needed;
      however, so far they are not available. This paper recommends the type of
      personnel and technical equipment needed for stress echocardiography
      laboratories, based on experience gained during more than 2000 stress
      echocardiographic procedures. To perform stress echocardiography, a cardiologist
      and a technical assistant--both well trained over a large number of tests--should
      be involved. The laboratory must have basic equipment such as a 12-lead ECG,
      blood pressure monitoring capacity, a treadmill or bicycle for ergometry, a
      precision intravenous delivery system for pharmacological stress testing as well
      as an adequate echo table; additionally, emergency equipment is mandatory. The
      ultrasound machine should contain transducers with high 2-D resolution; most
      important is a digital image acquisition system which facilitates performance and
      interpretation through side-by-side display of synchronized rest and stress
      images. Finally, there is a need for proper patient preparation and the obtaining
      of informed consent.

PMID- 9183611
TI  - Stress echocardiography: new techniques.
AB  - Stress echocardiography is frequently used to evaluate coronary artery disease,
      and also in quantitative assessment of right and left ventricular function or
      cardiac valve integrity in patients with cardiomyopathy or during chemotherapy.
      Various new ultrasound techniques in stress echocardiography are now playing a
      significant role in this important area of cardiological diagnostics. New methods
      of echocardiographic signal processing have been developed to provide more
      quantitative and reproducible information on cardiac function during stress. The
      most important are: (1) raw data analysis techniques for endocardial border
      detection (acoustic quantification, CK = colour kinesis), (2) tissue Doppler
      imaging for myocardial velocity analysis and (3) transpulmonary contrast agents
      (Albunex, Laevovist, BY 963) for improving endocardial border delineation and for
      future analysis of myocardial perfusion. Like all new techniques, they must first
      be subjected to comprehensive scientific assessment, and appropriate training
      should be given, taking into account physical and physiological limits. These
      limits will constantly be redefined as echocardiographic techniques continue to
      change presenting new challenges for the further development of ultrasound
      technology. In this review, the improved new techniques will be discussed in
      detail.

PMID- 9183612
TI  - Coronary artery disease--diagnosis of ischaemia: general considerations.
AB  - Stress echocardiography is a well established tool for the diagnosis of coronary
      artery disease. It combines the provocation of myocardial ischaemia (either
      dynamic or nondynamic) with images of the left ventricle obtained by two
      dimensional echocardiography. Different modalities can be used to unmask coronary
      artery disease: increase of myocardial oxygen demand (exercise, pacing, or
      dobutamine) or reduction in oxygen supply (dipyridamole). Each form of stress has
      its distinct characteristics such as haemodynamic changes, accuracy, feasibility,
      and adverse effect, which specifically influence the decision ?which test for
      which patient'. Before engaging in the task of performing stress
      echocardiography, the cardiologist must have undergone special training under the
      supervision of an experienced stress echocardiographer, followed by an individual
      learning curve of ?try out' studies without any diagnostic impact. While
      performing a stress echocardiographic examination one must always keep the
      history and risk profile of the individual patient in mind. These factors
      influence the pre-test likelihood of a patient having coronary artery disease,
      and therefore also the diagnostic merit of a stress test. While stress
      echocardiography is not the first test to be employed in patients with suspected
      coronary artery disease, it represents a diagnostic tool which, if used
      correctly, is likely to become the most important non-invasive technique in
      modern cardiology.

PMID- 9183613
TI  - Stress echocardiography in special groups: in women, in left bundle branch block,
      in hypertension and after heart transplantation.
AB  - The non-invasive diagnosis of coronary artery disease by exercise
      electrocardiography is less accurate in women than in men, with a high rate of
      false-positive results in women. In contrast, recent studies have demonstrated
      that stress echocardiography in women is more accurate than exercise
      echocardiography and that the significantly higher specificity of stress
      electrocardiography may have the benefit of avoiding unnecessary angiography in
      women. Exercise-induced changes in the electrocardiogram are non-diagnostic in
      the presence of left bundle branch block or basal ST changes. In these patients,
      stress echocardiography can be used instead of conventional scintigraphy for the
      detection of coronary artery disease, but further echocardiographic studies are
      needed to confirm the promising results. Exercise electrocardiography and
      exercise echocardiography have been reported to be disappointing in the early
      detection of cardiac allograft vasculopathy after heart transplantation, and
      dobutamine stress echocardiography overestimates the incidence of angiographic
      evidence of cardiac allograft vasculopathy. However, compared to intravascular
      ultrasound imaging, dobutamine stress echocardiography seems to be a suitable non
      invasive method for detecting cardiac allograft vasculopathy.

PMID- 9183614
TI  - Should the diagnosis of coronary artery disease be based on the evaluation of
      myocardial function or perfusion?
AB  - The aim of this review was to define the place of stress (exercise, dobutamine,
      and vasodilator) echocardiography in the context of perfusion scintigraphic
      techniques for the detection of coronary artery disease. Echocardiography and
      nuclear imaging have their strong and weak points. Echocardiography has the
      benefit of widespread availability, relatively low cost, portability, absence of
      radiation, safety, and determination of ischaemic threshold. However,
      echocardiographic imaging cannot be performed during treadmill exercise, the
      echocardiographic windows are variable with sometimes poor echogenicity, and
      interpretation is subjective and requires an important learning curve. Diagnostic
      comparisons were focused on studies involving echocardiographic and nuclear
      imaging in the same patients. These direct comparisons show that exercise or
      dobutamine echocardiography and perfusion imaging have similar accuracies for the
      detection and localization of coronary artery disease. Perfusion imaging may be
      more sensitive in the detection of mild coronary artery disease;
      echocardiography, however, has a better specificity. Vasodilator perfusion
      imaging is superior to vasodilator echocardiography, although the new
      dipyridamole-atropine echocardiography test will make future reassessment
      necessary. Once the condition of adequate echocardiographic training is
      fulfilled, we believe that the selection of one or other test should be tailored
      to clinical circumstances rather than be a uniform decision.

PMID- 9183615
TI  - Role of stress echocardiography in risk stratification early after an acute
      myocardial infarction. EPIC (Echo Persantin International Cooperative) and EDIC
      (Echo Dobutamine International Cooperative) Study Groups.
AB  - Resting and stress echocardiography is a 'one-stop shop', which enables a wide
      range of information to be collected on resting function, myocardial viability,
      and induced ischaemia, all of which are useful for prognostic stratification.
      Large scale, multicentre, prospectively collected data show the prognostic
      failure of resting function and inducible ischaemia, both independently and
      combined, which are especially effective in predicting cardiac death. The GISSI
      data show that the increment of risk as a result of reduction in ventricular
      function has a hyperbolic trend, with a relatively moderate increase in mortality
      for ejection fraction values between 50 and 30%, but with marked increases below
      30%. The EPIC data show that the 1-year risk of cardiac death is as low as 2% in
      patients with negative dipyridamole stress echocardiography: it doubles if the
      test is positive at a high dose, and is almost four times higher if it is
      positive at a low dose. In the field of prognostic stratification, in the absence
      of carefully controlled studies, the choice between coronary angiography as the
      only essential study, or use of a non-invasive test to discriminate access to
      catheterization currently reflect alternate philosophical approaches rather than
      scientifically based decisions. In the invasive approach, stress echocardiography
      offers relief from the vicious circle of chest pain-coronary angiography
      revascularization. In the non-invasive and physiological approach, stress echo is
      capable of offering, in one sitting, an insight into the main determinants of
      survival: function, viability, and ischaemia.

PMID- 9183616
TI  - Prognostic value of dobutamine-atropine stress echocardiography for peri
      operative and late cardiac events in patients scheduled for vascular surgery.
AB  - Cardiac events in the peri-operative phase and late after non-cardiac vascular
      surgery are a major cause of morbidity and mortality. Numerous tests and
      diagnostic strategies--usually consisting of a combination of analysis of
      clinical risk factors and additional non-exercise dependent stress testing, such
      as thallium scintigraphy, or stress echocardiography--have been developed to
      preoperatively identify patients with increased risk. The tests ideally should
      identify three subpopulations in a group with a high prevalence of coronary
      artery disease; (1) low-risk patients who can be referred for surgery without
      extra cardiac intervention. (2) patients whose peri-operative cardiac risk
      outweighs the potential benefits of vascular surgery, (3) patients whose risk may
      be reduced by peri-operative therapeutic interventions. This review will discuss
      the prognostic value of dobutamine stress echocardiography for risk
      stratification in patients scheduled for non-cardiac vascular surgery and discuss
      guidelines for future management.

PMID- 9183617
TI  - Use of stress echocardiography for the prognostic assessment of patients with
      stable chronic coronary artery disease.
AB  - Stress echocardiography has become an established tool for the diagnosis of
      coronary artery disease. However, in the current era of attention to cost
      effectiveness, the ability of a non-invasive test to predict outcomes, and
      therefore assist in clinical decision making, is paramount. As a reflection of
      the relative youth of this technique, there are fewer data using stress
      echocardiography to assess prognosis than there are using nuclear imaging.
      However, using both exercise and pharmacological stress echocardiography, the
      presence of ischaemia is strongly predictive of the recurrence of a subsequent
      cardiac event. Moreover, during pharmacological stress testing, the ischaemic
      threshold may be used to further stratify the risk of a positive test. More
      studies are needed in large populations to establish the prognostic role of
      stress echocardiography, as in independent predictor of outcome, incremental to
      clinical and stress testing data.

PMID- 9183618
TI  - Characterization of hibernating and stunned myocardium.
AB  - Both the hibernating and the stunned myocardium are characterized by reversible
      contractile dysfunction. In hibernating myocardium ischaemia is still ongoing,
      whereas in stunned myocardium blood flow is fully or almost fully restored. Both
      the hibernating and the stunned myocardium retain an inotropic reserve. In
      hibernating myocardium the increase in contractile function is at the expense of
      metabolic recovery whereas in stunned myocardium no metabolic deterioration
      occurs during inotropic stimulation. Therefore, inotropic stimulation in
      combination with metabolic imaging may help not only to identify viable,
      dysfunctional myocardium but also to distinguish between hibernating and stunned
      myocardium. The therapy of hibernating myocardium is to restore blood flow to the
      hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since
      by definition blood flow is normal and contractile function will recover
      spontaneously. If, however, myocardial stunning is severe, involves large parts
      of the left ventricle and thus impairs global left ventricular function, it can
      be reversed with inotropic agents and procedures. In the experimental setting,
      anti-oxidant agents, calcium antagonists and ACE inhibitors attenuate stunning,
      most effectively when administered before ischaemia.

PMID- 9183619
TI  - Detection of myocardial viability using stress echocardiography.
AB  - Asynergic myocardial regions in patients with coronary artery disease can be
      viable. They may have the ability to improve their function after restoring
      coronary blood flow. Asynergic but viable myocardial regions have a positive
      inotropic reserve which can be stimulated by catecholamines. Because
      echocardiography is an established method for evaluating regional left
      ventricular function, it has the potential to detect the inotropic response of
      asynergic myocardial regions. In the clinical setting, prediction of left
      ventricular functional improvement after revascularization is particularly
      important. Dobutamine stress echocardiography is the most frequently used stress
      echocardiographic test for detection of myocardial viability. Dobutamine is
      infused at low rates of 2.5 to 20 micrograms.kg-1.min-1 to detect myocardial
      viability. This paper reports on the sensitivity and specificity of the method
      for the detection of viability and its usefulness for prediction of left
      ventricular functional improvement after revascularization.

PMID- 9183620
TI  - Myocardial viability. Stress echocardiography vs nuclear medicine.
AB  - Myocardial dyssynergy does not necessarily indicate myocardial necrosis in
      patients with coronary artery disease. The differentiation between viable and non
      viable tissue is of great clinical importance in order to make the most
      appropriate clinical decision in the individual patient. Several techniques are
      used to assess myocardial viability. Nuclear medicine gives reliable information
      on regional perfusion, metabolism and cell membrane integrity, while
      echocardiography provides real time visualization of myocardial thickening in
      basal conditions and continuously during pharmacological interventions. The
      presence or absence of contractile reserve in akinetic regions can be evaluated
      by pharmacological stress echocardiography. This article presents the semiology
      of myocardial viability as characterized by these different methods and reviews
      their relative value in different clinical settings.

PMID- 9183621
TI  - FDG SPECT in the assessment of myocardial viability. Comparison with dobutamine
      echo.
AB  - The use of 18F-fluorodeoxyglucose (FDG) imaging with single photon emission
      computed tomography (SPECT) has been introduced recently to assess myocardial
      viability. Several centres have now gained experience with cardiac FDG SPECT
      imaging, and this report is a summary of the currently available FDG SPECT data.
      Three studies have compared FDG SPECT with FDG positron emission tomography and
      demonstrated good agreement between them. Initial results in patients undergoing
      revascularization suggest that FDG SPECT can predict improvement in contractile
      function after revascularization. Although the initial results are promising,
      larger studies are needed to determine the precise role of FDG SPECT in the
      assessment of myocardial viability.

PMID- 9183622
TI  - Stress echocardiography beyond coronary artery disease.
AB  - Doppler echocardiography has become the major diagnostic tool of evaluation of
      valvular heart disease and the cardiomyopathies because of its ability to provide
      valuable haemodynamic information accurately and non-invasively. It is therefore
      ideally suited for haemodynamic stress testing in these patients. In aortic
      stenosis, dobutamine echocardiography can distinguish severe from non-severe
      stenosis in patients with depressed left ventricular function, low transvalvular
      gradients, and a relatively small (flow-related) valve area at baseline. Patients
      with non-severe aortic stenosis increase cardiac output and valve area with
      dobutamine infusion while the transvalvular gradient does not change
      significantly. In severe aortic stenosis, the pressure gradient increases
      significantly with stroke volume, but valve area does not. In patients who fail
      to increase stroke volume (absent contractile reserve) and therefore do not show
      a change in haemodynamics, the severity of the lesion is 'indeterminate'; these
      patients are characterized by a very poor prognosis. In mitral stenosis, patients
      can be identified who increase valve area during exercise, which is the
      fundamental mechanism by which stroke volume can be increased in mitral stenosis.
      The increase in pulmonary artery pressure during exercise (assessed from
      tricuspid regurgitant signal) can be dramatically different in patients with
      comparable resting haemodynamics; therefore exercise echocardiography provides
      information which cannot be obtained from resting measurements alone and can help
      to guide medical and surgical therapy. Whether stress echocardiography may be
      similarly helpful in patients with regurgitant lesions is still a subject of
      investigation. Exercise Doppler echocardiographic studies following aortic valve
      replacement (small valves) can identify impairment of systolic and diastolic
      function indicative of 'valve prosthesis-patient mismatch'. In hypertrophic
      cardiomyopathy the dynamics of outflow obstruction can be assessed following
      exercise or pharmacological intervention. In dilative cardiomyopathy, contractile
      reserve can be assessed by dobutamine echocardiography which may help in
      evaluating prognosis, guiding heart failure therapy, and monitoring therapy with
      cardiotoxic chemotherapeutic agents.

PMID- 9183623
TI  - [A new look at the history of tumor immunotherapy--for its fruitful future
      through overcoming the widespread cynicism].
AB  - This review deals with a new look at the history of tumor immunotherapy by
      dividing that into four generations in the context of its recent scientific
      advance which gives a birth of a new paradigm to immunology and immunotherapy of
      human cancer. Tumor immunology was born in 1953 when the presence of tumor
      specific transplantation antigens was demonstrated in the animal models. All
      trials were nonsense in the 0 generation before its birth except for Coley's
      vaccine. The 1st generation (1953-1983) of immunotherapy after its birth was the
      period in which the nonspecific immunotherapy was enthusiastically attempted too
      much without knowledge of specific tumor immunity, only to result in the cynicism
      of tumor immunology and immunotherapy. After this, new important discoveries in
      tumor immunology have been followed successively in animal models, giving a
      scientific basis to immunotherapy of human cancer. The key discoveries in human
      tumor immunology, however, have been done since 1986 when first adoptive
      immunotherapy with autologous CTL from patient's tumor was attempted. Thus,
      immunotherapy from 1983 to 1986 and that from 1986 to present are separately
      reviewed in this paper as the 2nd generation and the 3rd generation,
      respectively.

PMID- 9183625
TI  - [Prospects for antisense therapy of human leukemias].
AB  - Recent progress in cloning of pathogenic genes and technical advance in the
      synthesis of antisense oligodeoxynucleotides (AS ODN) analogues have spurred a
      research effort dedicated to the development of antisense therapy for cancer and
      viral diseases. We have reported that phosphorothioate AS ODN could effectively
      inhibit the abnormal expression of activated or rearranged oncogenes and lead to
      the growth suppression of leukemic cells in vitro by the induction of apoptosis.
      In this article, the state of art in antisense research and the feasibility of
      antisense therapy for leukemia are also discussed.

PMID- 9183624
TI  - [Regulatory mechanisms of lymphocyte proliferation: roles of Spa-1 gene].
AB  - Spa-1 genes is one of the secondary response genes specifically induced to
      express in the lymphoid cells following the mitogenic stimulations by antigens or
      mitogenic cytokines. Gene transfection experiments indicate that Spa-1 protein
      exhibits negative effect on cell growth and induces cell death when ectopically
      overexpressed. Spa-1 protein is a nuclear protein and suggested to function
      through the interaction with Ran, so far the only small G protein present in the
      nuclei, While Spa-1 mRNA is expressed in normal proliferating lymphocytes as well
      as factor-dependent cell lines, little mRNA is expressed in autonomously growing
      leukemic lines, suggesting the active repression of Spa-1 transcription in
      transformed cells. Analysis of this mechanism may provide a new insight into the
      transformation processes in lymphoid cells.

PMID- 9183626
TI  - [Recombinant virus-mediated transfer of the wild-type p53 gene is a potent
      therapeutic strategy for human cancer].
AB  - Tumor suppressor p53 gene, which is most commonly mutated in human cancers, plays
      an important role in the control of cell cycle and the induction of apoptosis
      (programmed cell death). Transfection of the wild-type p53 gene into tumor cells
      induced either growth suppression or apoptosis. We have examined the effect of
      the recombinant retroviral or adenoviral vector expressing the wild-type p53 gene
      on the tumor cell proliferation as well as on the sensitivity of infected-tumor
      cells to various anticancer agents. The possible application of recombinant virus
      mediated direct in vivo transfer of the wild-type p53 gene to human cancer
      therapy will be discussed.

PMID- 9183627
TI  - [Mechanism of the lymph node metastasis in human esophageal cancer (epidermal
      growth factor causes the dysfunction of cadherin-mediated cell-cell adhesion)].
AB  - Previous studies reported that the overexpression of the epidermal growth factor
      receptor (EGF-R) and reduced expression of E-cadherin and alpha-catein were
      associated with lymph node metastasis of the esophageal cancer. In the present
      study, we examined that epidermal growth factor (EGF) caused in part the
      dysfunction of cadherin-mediated cell-cell adhesion using the human esophageal
      cancer cell line (TE-2R), which expressed E-cadherin and EGF-R. In the presence
      of EGF, TE-2R changed its colony formation from compact to sparse. In the cell
      dissociation assay, EGF strongly facilitated the dissociation of TE-2R cells in a
      dose-dependent manner. Moreover, EGF enabled the cells to invade in organotypic
      raft culture. These phenomena were accompanied not by decreased expression of the
      E-cadherin molecule but by a change in its localisation from the lateral adhesion
      site to the whole cell surface. Finally, we observed tyrosine phosphorylation of
      beta-catenin induced by EGF. These results might suggest that EGF counteracts E
      cadherin mediated cell-cell adhesion through phosphorylation of beta-catenin and
      modulates tumor cell behaviour to a more aggressive phenotype for lymph node
      metastasis of the esophageal cancer.

PMID- 9183628
TI  - [Disruption of genomic imprinting in human carcinogenesis].
AB  - Several lines of evidence have suggested that the accumulation of specific gene
      alterations such as the activation of proto-oncogenes and the silencing of
      suppressor genes is indispensable for tumorigenesis. In addition, recent
      molecular studies demonstrated that epigenetic alteration also have an important
      role in the initiation and progression of human cancers. In particular, the
      parent-of-origin specific gene modification, named genomic imprinting, has been
      demonstrated to play a causative roles in several human cancers including renal
      tumors of childhood. Although the precise mechanisms of genomic imprinting have
      not been clarified yet, it is obvious that the DNA methylation could be one of
      the key machinery to regulate differential expression of genes. In near future,
      the rapid advance in molecular genetics of human cancer will be expected in terms
      of epigenetic modification of cancer-associated genes.

PMID- 9183629
TI  - Effect of cadmium injury on growth and migration of cultured human vascular
      endothelial cells.
AB  - The effect of cadmium chloride (CdCl2) on the cell proliferation and migration of
      cultured human umbilical vein endothelial cells (HUVECs) was quantitatively
      analyzed. The HUVEC viable cell count decreased dose-dependently after exposure
      to Cd (cadmium chloride, 10 nM-1 mM). Morphologic examination by phase-contrast
      microscopy revealed severe damaging effects of Cd at higher concentrations. The
      cytotoxic effect of Cd (10 microM-1 mM) on DNA synthesis was also concentration
      dependent. When the distance endothelial cells grew out from the scraped edge of
      a monolayer was measured, HUVEC outgrowth was found to be inhibited by Cd (1.0
      microM-1.0 mM) in a dose-dependent manner. These findings suggest that HUVEC cell
      proliferation and migration are susceptible to Cd cytotoxicity, and that this may
      be involved in the pathogenesis of atherosclerosis.

PMID- 9183630
TI  - Establishment and characterization of two human bladder cancer cell lines.
AB  - Two cell lines, SNK57 and NKB1, were established from human bladder cancer: SNK57
      from a transitional cell carcinoma (TCC) in a 73-year-old female and NKB1 from a
      residual TCC following MEC (methotrexate, farmorubicin and cisplatin)
      chemotherapy in a 64-year-old female. Doubling time of SNK57 and NKB1 cells was
      24 hours and 45 hours, respectively. The chromosome number of both cell lines was
      100 percent anueploid with a mode of 43 chromosomes for SNK57 and 107 for NKK1.
      Both SNK57 and NKK1 induced tumors at the site of subcutaneous injection of nude
      mice. Histology of the tumors closely resembled that of the original ones from
      which they were derived. Although NKB1 was 4 times more resistant to doxorubicin
      (ADM) as compared to SNK57, overexpression of MDR1 gene product, P-glycoprotein
      was not evident in NKB1 as well as SNK57. These two new cell lines with different
      chemosensitivity to ADM may be a useful model for developing new chemotherapeutic
      strategies for human bladder cancer.

PMID- 9183631
TI  - Establishment and characterization of human acute lymphoblastic leukemia cell
      lines, BALM-13 and BALM-14, with intraclonal phenotypic heterogeneity.
AB  - Two new B-cell lines, BALM-13 and BALM-14, were established from the bone marrow
      aspirate of a 13-year-old male patient with acute leukemia. These cell lines are
      unique in their expression of CD antigens. BALM-13 was characterized as belonging
      to the Burkitt lymphoma group III cell type (CD10-, CD20+, CD23+, D39+, CD77-),
      and BALM-14 to the Burkitt lymphoma group I cell type (CD10+, CD20+, CD23-, CD39
      , CD77+). The expression of immunoglobulin chains of BALM-13 (lambda delta mu)
      differed from those of BALM-14 (lambda mu). Furthermore, BALM-13 was positive for
      Epstein-Barr virus nuclear antigen but BALM-14 was negative. This is a unique
      pair of cell lines having intraclonal phenotypic heterogeneity.

PMID- 9183632
TI  - Effect of hyperthermia on proliferation and deviation of carcinoembryonic antigen
      and squamous cell carcinoma-related antigen of human esophageal carcinoma cells
      in culture.
AB  - As a basic study of hyperthermia on malignant tumors, we investigated the
      kinetics of proliferative activity and the values of tumor markers
      carcinoembryonic antigen (CEA) and squamous cell carcinoma-related antigen (SCC)
      in a human esophageal carcinoma cell line, SGF-4, following a change of culture
      temperature. The temperature range allowing cultured SGF-4 cells to proliferate
      was from 37 degrees C to 40 degrees C. In an experiment examining the recovery of
      proliferative activity, no proliferative activity was observed after the cultured
      cells were exposed to 42 degrees C for 72 hours. The values of CEA and SCC as
      tumor markers were found to be increased in association with the cell damage due
      to the change of temperature. These markers could thus be useful as indicators
      for evaluations of hyperthermia therapy effectiveness.

PMID- 9183633
TI  - [Mechanism of cisplatin and peplomycin therapy on head and neck carcinoma].
AB  - Results of chemotherapy for head and neck cancer are now improving owing to the
      development of concomitant use of chemotherapeutic agents such as cisplatin or
      peplomycin. Concomitant use of the two agents has been favored clinically.
      However, fundamental study on the combination therapy has not been carried out
      sufficiently. In the present study we studied the cell kinetics of tumor cells by
      the combination of cisplatin and peplomycin using flowcytometric analysis and
      electron microscopy. Survival of tumor cells was lowest, when peplomycin was
      administrated 3 days after cisplatin. Cell kinetics showed an accumulation at the
      S and G2M stage in this situation, By the electron microscopic study, microvilli
      of tumor cells disappeared and the blebbing of tumor cells was observed, when
      cisplatin alone was administrated. However, when the combination of cisplatin and
      peplomycin was administrated to the tumor cells, tumor cells enlarged. The
      results suggest that the mechanism of combination therapy differed from the
      mechanism of cisplatin alone.

PMID- 9183634
TI  - [A PTHrP-producing cell line derived from human small cell lung carcinoma].
AB  - We established a cell line, designated MS-1, from pleural effusion of a 54-yrs
      old male patient with small cell lung carcinoma. MS-1 cells grew as a floating in
      RPMI-1640 medium supplemented with 10% FBS and the population doubling time was
      45 hours. The chromosome number ranged from 49 to 52 and structural abnormalities
      of 1p+, 3q-, 6p-, 14p+ and 17p+ were observed in all the cells examined. MS-1
      cells released PTHrP into the conditioned medium and heterogeneity of the PTHrP
      molecule produced in the cells was found in the gel permeation chromatography.
      Expression of the PTHrP gene as well as presence of the PTHrP protein in the
      cells were confirmed by reverse-transcriptase PCR(RT-PCR) and immunohistochemical
      staining. These findings indicate that MS-1 cells are derived from human small
      cell lung carcinoma, which produce PTHrP.

PMID- 9183635
TI  - [Proliferation and differentiation of human salivary gland adenocarcinoma cell
      line HSG].
AB  - The adenocarcinoma cell line derived from an intercalated ductal epithelium of a
      human salivary gland (HSG) proliferates autonomously mediated by an epidermal
      growth factor-(EGF)-like molecule with a molecular weight of 46 kDa and an EGF
      receptor (EGFR). The c-erbB2 protein, a member of EGFR family was also expressed
      in HSG cells and was involved in the growth signal pathway of HSG cells as well
      as EGFR. The autocrine growth is regulated by glucocorticoid and retinoic acid
      (RA) via their receptors. Retinoic acid receptor (RAR) of HSG cells revealed a
      transcriptional activity in vivo, and the heterodimerization between RAR and 9
      cis retinoic acid receptor (RXR) is requisite for the binding with a specific DNA
      element termed RA response element in vitro. RXR alpha and RXR beta were cloned
      from HSG cells, and these RXRs, together with RAR, seemed to play a physiological
      role in RA signaling in vivo.

PMID- 9183636
TI  - Fabrication of cultured epithelium using oral mucosal cells and its clinical
      applications.
AB  - A cultured mucosal epithelium can be formed with living mucosal cells in vitro
      and used as a graft material. In this article, we described our culture methods
      for preparation of cultured mucosal epithelium as well as its biological
      characteristics compared with cultured skin epithelium. According to our results,
      cultured mucosal epithelium was formed earlier than cultured skin epithelium.
      Furthermore, the structure of cultured mucosal epithelium was maintained longer
      than that of cultured skin epithelium. Based on our findings from an in vitro
      study, we applied this cultured mucosal epithelium to the reconstruction of human
      skin and mucosal defects and succeeded in repairing the defects. We also present
      an overview of the problem relevant to the use of such methods.

PMID- 9183637
TI  - Establishment of two human renal cell carcinoma cell lines with different
      chemosensitivity.
AB  - Two cell lines, SKR1 and NKK1, were established from renal cell carcinomas (RCC)
      with different histopathologic characteristics: SKR1 from grade 3, solid type,
      pleomorphic cell type carcinoma in a 66-year-old male and NKK1 from grade 2,
      alveolar type, clear cell carcinoma in a 49-year-old female. Electron microscopic
      study showed the presence of microvilli on cell surface and desmosome-like
      structures between cells in both lines. Doubling time and plating efficiency of
      SKR1 were 28 h and 37%, respectively, whereas those of NKK1 were 45 h and 22%,
      respectively. The chromosome number of both cell lines was 100% aneuploid with a
      mode of 74 chromosomes for SKR1 and 84 for NKK1. Both SKR1 and NKK1 induced
      tumors at the site of subcutaneous injection of nude mice. The morphologic
      characteristics of the tumor were similar to those of each original tumor. NKK1
      was about 20 times more resistant to doxorubicin and vinblastine as compared to
      SKR1. Expression of P-glycoprotein was considered to be one of the factors
      responsible for such multidrug resistant phenotype of NKK1 cells. These two lines
      with different chemosensitivity may be a useful model for developing new
      therapeutic strategies for RCC.

PMID- 9183639
TI  - Copper enhances EDNO (endothelium-derived nitric oxide) activity by cultured
      human vascular endothelial cells.
AB  - The effect of copper sulfate (Cu) on viable cell number, endothelium-derived
      nitric oxide (EDNO), and nitric oxide synthase (NOS) in cultured human umbilical
      vascular endothelial cells (HUVEC) was investigated. The viable cell number was
      not affected by the addition of Cu (1.0-500.0 microM). To assess the effect of
      EDNO by HUVEC, platelet aggregation experiments were performed, using cuvettes
      lined with HUVEC. Thrombin (0.05 units/ml)-induced platelet aggregation was
      markedly inhibited in the presence of HUVEC compared with aggregation in the
      absence of HUVEC. The HUVEC-dependent anti-platelet aggregatory effect was
      slightly reduced when HUVEC were pretreated with indomethacin (IND; 1.0 micro M),
      an inhibitor of the cyclo-oxygenase pathway. However, the thrombin-induced
      platelet aggregation in the presence of HUVEC pretreated with IND was smaller
      than that in the absence of HUVEC, which is dependent on EDNO. The anti-platelet
      aggregatory effect of HUVEC pretreated with IND was increased dose-dependently by
      48-hour pretreatment of HUVEC with Cu (1.0-100.0 microM). To assess the effect of
      Cu on NOS, HUVEC were stained with NOS/NADPH diaphorase. However, there were no
      significant differences in the NOS-positive HUVEC cell count between cells
      without Cu and those with various concentrations of Cu. These findings suggest
      that Cu stimulates the activity of EDNO, which action may be dependent on Cu
      decreasing EDNO-oxidative damage.

PMID- 9183638
TI  - Establishment of eighteen clones of Ishikawa cells.
AB  - Ishikawa cells, which derive from a well differentiated human endometrial
      adenocarcinoma, were cloned using the limiting dilution method in an attempt to
      preserve well differentiated cells. Eighteen clones were obtained. According to
      their morphologic characteristics, there were six well differentiated, seven
      moderately differentiated, three poorly differentiated and two adenosquamous
      carcinoma clones. All of them were transplantable into node mice. Fifteen of the
      17 clones were positive for estrogen receptors and all of the clones examined
      were positive for progesterone receptors. There were no significant differences
      in terms of population doubling time, plating efficiency or saturation density
      among these clones. On the basis of these results, we concluded that Ishikawa
      cells are not as homogeneous morphologically as we thought, since cells with
      varying degrees of differentiation have already mingled with the parent cell
      line. It is verified that the adenosquamous cell carcinoma of the endometrium can
      arise from one stem cell. It would be impossible to revive the cultured cells
      after having undergone their changes to the original conditions. Therefore, to
      preserve the characteristics of an established cell line, the cells should be
      frozen at a very early stage. It is also important to avoid frequent passages
      when special characters of the cells are necessary for a given investigation.

PMID- 9183640
TI  - [Establishment of human glioblastoma cell line "TK-1"].

PMID- 9183641
TI  - [Effect of recombinant human basic fibroblast growth factor (bFGF) on the growth
      of human tumor cell lines].
AB  - Effect of bFGF on the growth of 24 human tumor cells (established cell lines of
      epithelium series, mesenchymal series, muscle cell series, and nervous system
      series) was investigated in vitro. Of 24 cell lines examined, bFGF accelerated
      the growth of 6 cell lines including[A431(epidermoid carcinoma), KB (epidermoid
      carcinoma), HuH28 (bile duct carcinoma), YMB-1 (breast carcinoma), SW1353
      (chondrosarcoma) and SKN(leiomyosarcoma)]. Epidermal growth factor (EGF) and
      transforming growth factor alpha (TGF alpha), utilized as control growth factors,
      also accelerated the growth of HuH28, SW1353 and SKN, and HuH28 and SKN,
      respectively. On the other hand, transforming growth factor beta 1(TGF beta 1),
      inhibited the growth of variety of cell lines and acceleration on cell growth was
      not recognized. These findings demonstrate the bFGF, as well as other growth
      factors, was found to promote the growth of a few cell lines investigated and
      that further experiments including in vivo studies will be needed. In conclusion,
      majority of the cell lines examined in this study seem to proliferate by their
      own endogenous growth factor(s) but not by exogenous bFGF.

PMID- 9183642
TI  - Human cells and cell cultures: availability, authentication and future prospects.
AB  - The availability of well characterized, viable human cells, tissues and cell
      lines along with pertinent data on the specific patient donors is a prerequisite
      for much current transplantation and biomedical research. In the USA,
      institutional and multi-center networks have been established for provision of
      primary human cells and tissues to qualified clinicians and research scientists.
      Monetary support derives from government, university, institutional and fee
      sources. Problems involved include concern for the rights and privacy of tissue
      donors, cultural reservations relating to tissue provision, the need for safe and
      expeditious transport, short term survival and limited supply, adequate
      correlation of patient data with samples provided, presence of infectious viruses
      and microorganisms, as well as state or government regulations regarding national
      or international shipping. The use of human cell lines with continuous or even
      somewhat limited doubling potentials overcomes many of the above difficulties.
      National cell banks have been established to provide reference lines for use by
      multiple investigators. Use of such cell lines assures improved research
      comparability both geographically and with time. Authentication procedures are
      critically important for all of these programs. Verification of tissue types and
      conditions is required through histological, biochemical and immunological
      assays. Tests for microbial and viral contaminants must be applied. In addition
      to such procedures utilized for tissues, with cell lines the banking agency must
      also verify species and where possible identity, properties and functions. The
      literature is replete with descriptions documenting incorrect identifications and
      infections of proliferating cell strains used for research. The availability of
      viable tissue through local sources and distribution agencies in the USA is
      becoming more commonplace even including full family participation and collection
      of related, detailed histories. Increased support for this developmental activity
      is needed, coupled with provision of blood and normal cells and cell lines from
      family members in many disease categories. Modern techniques, new and improved
      culture ware, serum-free media, reagents such as growth, adherence and transfer
      factors will permit isolation, propagation and wide spread distribution not only
      of human tumor cells but also normal and functional human cells of most renewing
      and expanding tissue types. Hybridization and immortalization techniques are
      enhancing this capability such that virtually all human cell types should be
      available for short or longer-term propagation and study in the foreseeable
      future.

PMID- 9183643
TI  - Role of CD26 for CD4 memory T cell function and activation.
AB  - CD26 is a 110 kDa T cell activation antigen and has been shown to have DPPIV
      enzyme activity which cleaves amino-terminal dipeptides with either L-proline or
      L-alanine at the penultimate position. Recent studies showed that CD26 plays an
      integral role in T cell activation. A partial explanation of the mechanism of
      CD26 mediated T cell signaling appears to be its association with CD45 tyrosine
      phosphatase, which may be importance in T cell activation and signal
      transduction. In addition, we showed that CD26 is a receptor for adenosine
      deaminase (ADA). Moreover, ADA on the cell surface is involved in an important
      immunoregulatory mechanism by which released ADA binds to cell surface CD26 and
      this complex is capable of reducing the local concentration of adenosine. Thus,
      CD26 is a multifunctional molecule controlling many key aspects of lymphocyte
      function.

PMID- 9183644
TI  - Beta 1 integrin-mediated signaling in human T cells.
AB  - Beta 1 integrin/ligand binding evokes tyrosine phosphorylation of various
      proteins. In our previous studies, we have shown that the engagement of beta
      integrin molecules induced tyrosine phosphorylation of 140, 120, 110-105, 80-70,
      60-55 and 45 KD proteins in peripheral T lymphocytes. Several tyrosine
      phosphorylated proteins have been identified such as PLC gamma (pp140),
      pp125FAK(pp120), Paxillin(pp70), p59fyn/p56lck(pp60-55) and MAPkinase (pp45).
      However, a 105 KD tyrosine-phosphorylated protein(pp105) has not been identified.
      Recently, we demonstrated that pp105 is identified as a novel p130Cas related
      protein. pp105 is preferentially expressed in lymphoid cells, while p130Cas is
      expressed in adherent cells. With these findings, we designated pp105 as Cas-L,
      "lymphocyte type Cas." Cas-L is directly associated with FAk-C-terminal region in
      an integrin stimulation-dependent manner, and tyrosine phosphorylated Cas-L binds
      to the SH2 domains of Crk, Nck and SHPTP2. These findings reveal a novel
      architecture of beta 1 integrin-mediated protein tyrosine phosphorylation and
      further suggest the involvement of Crk, Nck and SHPTP2 in the downstream of beta
      1 integrin-mediated signaling pathway.

PMID- 9183646
TI  - Intracellular signaling pathways and the regulation of cell adhesion.
AB  - Adhesion molecules play an essential role in the host immune response by
      mediating the adhesive interactions that are essential for immune cell
      trafficking and activation. Integrins are one family of adhesion receptors that
      leukocytes utilize to interact with other cells and with components of the
      extracellular matrix. Since leukocytes rapidly alternate between adhesive and
      nonadhesive states, the functional activity of integrins expressed on leukocytes
      is carefully and precisely regulated. Resting T lymphocytes express integrin
      receptors, but they mediate minimal cell adhesion. However, activation of the T
      cell results within minutes in increased integrin functional activity that occurs
      without a change in the level of integrin expression on the cell surface.
      Increased integrin-mediated adhesion appears to be a general response of T cells
      to activation, since a diverse array of activation stimuli are capable of
      inducing this rapid increase in integrin functional activity. We have used DNA
      mediated gene transfer and site-directed mutagenesis to elucidate the
      intracellular signaling pathways that regulate integrin-mediated cell adhesion.
      Our studies have revealed two important general themes. First, the lipid kinase
      phosphatidylinositol 3-kinase (PI 3-K) plays a role in integrin regulation
      mediated by many regulators of integrin function. Second, there are cell-specific
      differences in the signaling pathways that regulate integrin function. These
      studies illustrate the complex nature of the signaling pathways that regulate
      lymphocyte adhesion.

PMID- 9183645
TI  - Tyrosine phosphorylation of p130Cas in cell adhesion and transformation.
AB  - Integrins comprise the major class of receptors used by cells to interact with
      the extracellular matrix. Integrin/matrix interactions play a critical role in a
      variety of biological processes, including embryonic development, wound healing,
      tumor metastasis, cell growth and differentiation. It is now evident that
      integrins can transduce biochemical signals across the plasma membrane to the
      cell interior. Protein tyrosine phosphorylation has attracted much attention as
      an important regulator for integrin-mediated signal transduction. Recently, we
      have identified a novel signaling molecule, p130Cas, which participates in
      integrin-mediated signal transduction. p130Cas was originally identified as a
      protein hyperphosphorylated in cells expressing transforming gene products p47v
      crk (v-Crk) and p60v-crk (v-Src). In this brief review, we will discuss about a
      role of p130Cas in signal transduction triggered by cell adhesion and
      transformation.

PMID- 9183647
TI  - Integrins in cell adhesion and signaling.
AB  - Cell adhesive interactions play important roles during many normal physiological
      processes such as embryonic development and wound repair, and also during the
      progression of diseases such as cancer. Cell adhesion is mediated by the specific
      interactions of cell surface receptors with extracellular glycoproteins. The best
      characterized cell adhesion receptors are the integrins. Integrins comprise a
      family of more than 23 noncovalent, heterodimeric complexes consisting of an
      alpha and a beta subunit. Each subunit is a glycoprotein with a large, globular
      extracellular domain and a transmembrane domain. Most integrins have relatively
      small cytoplasmic domains consisting of fewer than 60 amino acids. Although many
      integrins can bind fibronectin, the alpha 5, beta 1, integrin is the major
      fibronectin receptor on most cells. This integrin mediates such cellular
      responses to fibronectin substrates as adhesion, migration, assembly of
      extracellular matrix, and signal transduction. Integrin ligands, such as
      fibronectin, are not passive adhesive molecules but are active participants in
      the cell adhesive process that leads to signal transduction. The best
      characterized integrin ligand is fibronectin. Fibronectin is a multifunctional
      glycoprotein comprised of three different types of homologous repeating units
      (termed type I, type II, and type III). Fibronectin has at least two independent
      cell adhesive regions: one located near the center of the polypeptide chain in
      the ninth and tenth type III modules binds to the alpha 5 beta 1 integrin. The
      biological function of the central cell adhesive region requires two critical
      amino acid sequences--an Arg-Gly-Asp (RGD) sequence and a Pro-His-Ser-Arg-Asn
      (PHSRN) sequence, which function in synergy--for optimal binding to the alpha 5
      beta 1 integrin. Furthermore, the spacing between the crucial RGD and PHSRN
      sequences is also important for activity, suggesting the sequences themselves are
      necessary, but not sufficient, to account for the cell adhesive activity of
      fibronectin. One of the manifestations of integrin-mediated signal transduction
      including protein tyrosine phosphorylation. One cytoplasmic protein that is
      phosphorylated in response to cell adhesion is the focal adhesion kinase known as
      pp125FAK or FAK. The beta 1, beta 3, and beta 5 integrin intracellular domains
      are sufficient to initiate signal transduction pathways. Furthermore, alternative
      splicing can regulate the ability of beta integrin intracellular domains to
      participate in signal transduction. Other intracellular responses to cell
      adhesion include stimulation of migration, the assembly of an F-actin
      cytoskeleton and specialized structures called focal contacts, changes of
      cytoplasmic pH and calcium ion concentration, and modulation of proliferation and
      gene expression. Such varied modes of signal transduction are probably
      differentially controlled by a mechanism that requires either integrin receptor
      clustering alone, ligand occupancy in addition to clustering, or clustering
      and/or ligand occupancy plus tyrosine kinase activity for different responses.
      The examination of the fundamental mechanisms important for adhesion of cultured
      human cells and the resultant signaling processes has the potential of providing
      an understanding of molecular mechanisms involved in complex physiological
      processes and serving the basis for the development of novel therapeutic agents
      for the treatment of human disease.

PMID- 9183648
TI  - The role of VCAM-1 molecule in the pathogenesis of rheumatoid synovitis.
AB  - The present review focuses on the possible role of VCAM-1 expression on synovial
      fibroblast-like cells in the synovial lesion of rheumatoid arthritis (RA). The
      VCAM-1 expressing cells were mainly present in the synovial lining layer. The
      VCAM-1 expressing fibroblast-like cells also showed activity of uridine
      diphosphoglucose dehydrogenase, indicating that they are activated fibroblasts.
      VCAM-1 expressing T cells were also found in RA synovial fluids, where T
      lymphocytes show upregulation of alpha 4 beta 1 expression, and these T
      lymphocytes are able to bind to VCAM-1 in solid phase. Further experiments
      excluded the production of VCAM-1 protein in synovial fluid T lymphocytes and
      supported the idea that the soluble VCAM-1 was bound to the surface of synovial
      fluid T lymphocytes. We next planned to examine the effect of soluble VCAM-1 on T
      cell functions, by using recombinant soluble VCAM-1. The recombinant soluble VCAM
      1 rendered synovial or peripheral T cells anergic to various stimuli. These
      findings imply that recombinant soluble VCAM-1 might be useful as a therapeutic
      tool to prevent abnormal immune response, since it binds to activated T
      lymphocytes with upregulation of alpha 4 beta 1, but not to resting T
      lymphocytes, and soluble VCAM-1 bound T lymphocytes become anergic.

PMID- 9183649
TI  - A brief overview of apoptosis.
AB  - Apoptosis, a characteristic type of cell death, plays important roles in tissue
      and organ development in ontogeny. It also relates to the occurrence of serious
      diseases such as virus infection, autoimmune disease and cancer. Furthermore many
      drugs such as anticancer agents express their cytotoxicity via induction of
      apoptosis in the target cells. This article summarize the recent studies on
      apoptosis in view of its molecular mechanism and the relation to diseases.

PMID- 9183650
TI  - Apoptotic human SH-SY5Y neuroblastoma cells have regularly spaced single strand
      DNA breaks and increased DNA-dependent protein kinase activity.
AB  - SH-SY5Y human neuroblastoma cells died by apoptosis when treated with
      staurosporine or ceramide. The treated cells had both the nuclear morphology and
      patterns of DNA fragmentation which are characteristic of apoptosis. Higher order
      DNA fragments separable by pulse field gel electrophoresis were shown to contain
      regularly spaced single-strand nicks by producing a laddered pattern upon alkali
      treatment. Further evidence of DNA damage in treated cells was shown by increased
      activity of DNA-dependent protein kinase. This human cell model may prove useful
      in delineating the role of a cellular repair response to DNA damage prior to the
      irreversible steps of the cell death program.

PMID- 9183651
TI  - Neuronal apoptosis by glial NO: involvement of inhibition of glyceraldehyde-3
      phosphate dehydrogenase.
AB  - In primary cocultures of neurons and glial cells prepared from the neonatal rat
      brain, lipopolysaccharide (LPS) reduced the numbers of neuronal cells but the
      effects were markedly inhibited by NG-monomethyl-L-arginine, indicating the
      involvement of NO and LPS-induced NO synthase in neuronal death. LPS stimulated
      the expression of inducible NOS (iNOS) in preparations of primary cultured
      microglias/astrocytes, but not in primary cultured neurons. In addition, LPS
      caused DNA fragmentation only in NG108-15 cells but not in primary cultured
      astrocytes as well as astrocytes in cocultures of the two cell types, suggesting
      that NOS induces the apoptosis of neurons but not glial cells. We then examined
      the NO-induced neuronal death in NG108-15 cells using NO donors. SNP, and NO
      donor, caused NO-2 accumulation in the reaction medium and lactate dehydrogenase
      (LDH) leakage from NG108-15 cells. Although SNP stimulated guanylyl cyclase and
      accumulated cGMP, cGMP analogs did not affect LDH leakage. In addition, SNP
      induced chromosomal condensation and fragmentation of nuclei in NG108-15 cells.
      Gel electrophoretic analysis of cellular DNA extracted from SNP-treated cells,
      confirmed the internucleosomal DNA fragmentation typical of apoptosis in this
      culture. SNP increased the amount of radioisotopic labeled glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) in the presence of [32P]NAD and inhibited the
      enzyme activity. The results suggested that SNP-induced cell death is partly due
      to the NO-induced inhibition of GAPDH, perhaps by stimulating the binding of NAD
      to GAPDH.

PMID- 9183652
TI  - Regulation of neutrophil apoptosis--its biological significance in inflammation
      and the immune response.
AB  - Neutrophils play a pivotal role in host defence against bacterial infection.
      Their life span is short compared with that of leukocytes of other lineages.
      Neutrophils are programmed to die by apoptosis at the time of differentiation.
      However, recent studies have demonstrated that environment also has a great
      influence on apoptosis of these cells. Based on our recent experimental results,
      we present here a review of studies on the regulation of neutrophil apoptosis and
      discuss its biological significance in inflammation and the immune response.

PMID- 9183653
TI  - Apoptosis in cancer.
AB  - Apoptosis is a genetically encoded cell death program and plays an important role
      in the regulation of both normal and malignant processes. Recently, many factors
      involved in the control of apoptosis have been isolated and characterized, and
      thereby studies on the molecular mechanism of the signaling pathway of apoptosis
      have made rapid progress. In this article, we discuss the role of apoptosis in
      carcinogenesis and the possible ways to apply apoptosis to cancer therapy.

PMID- 9183655
TI  - Cadmium injures tube formation by cultured human vascular endothelial cells.
AB  - The effect of cadmium chloride (Cd; CdCl2) on the tube formation by cultured
      human umbilical vascular endothelial cells (HUVEC) was examined. HUVEC were
      collected by enzymatic digestion with collagenase. Tube formation was studied by
      culturing the cells on a gelled basement membrane matrix (Matrigel). Treatment of
      HUVEC with 0.1 microM-1.0 mM Cd for 24 hours inhibited tube formation dose
      dependently. The cadmium concentration inhibiting tube formation by 50% relative
      to untreated cells was about 150 microM. The length of tube formation decreased
      time-dependently with 150 microM Cd. The treatment of HUVEC by 50 nM of beta
      phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C,
      increased tube formation. However, the inhibitory effect of Cd on tube formation
      was not affected by the addition of PMA. The pretreatment of the Matrigel by Cd
      inhibited tube formation similarly to the results of Cd treatment. These findings
      suggest that Cd inhibits the formation of a capillary network by HUVEC, and that
      the Cd-inhibitory effect on tube formation may have been dependent in this study
      on the degeneration of Matrigel by Cd.

PMID- 9183654
TI  - Alterations of transforming growth factor-beta 1 receptor type II occur in
      ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and
      esophageal carcinomas, but not in gastric neoplasms.
AB  - BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative
      colitis (UC)-associated colorectal carcinomas and dysplasias manifest
      microsatellite instability (MI); however, esophageal carcinomas rarely exhibit
      MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta
      1RII) mutation in a coding microsatellite was described in primary colorectal
      carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed
      mechanisms of inactivation other than MI in human tumors; furthermore, MI
      negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated
      138 primary human neoplasms for mutation in the poly-A microsatellite tract of
      TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the
      expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined
      whether MI was present at other chromosomal loci in these lesions. The poly
      deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region
      was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was
      performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17
      MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2
      cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1
      dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers,
      contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors
      contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6
      cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT
      PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta
      1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal
      cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta
      1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this
      gene other than MI play a role in esophageal carcinogenesis.

PMID- 9183656
TI  - Induction and reversal of cell adhesion-dependent multicellular drug resistance
      in solid breast tumors.
AB  - Although there are a number of chemotherapeutic drugs available for the treatment
      of breast cancer, eg. adriamycin, cyclophosphamide and taxol, their effectiveness
      is severely limited by expression of intrinsic resistance in some patients and by
      acquired resistance in others. There is thus an urgent need to develop innovative
      methods to try and make these drugs more effective than is currently the case.
      One such method is to combine them with novel "chemosensitizers", i.e., drugs
      which themselves lack anti-tumor cytotoxic properties but which will increase the
      efficacy of those which do. In this regard we hae been studying the hypothesis
      that the resistance of solid tumors, including breast cancer, can be expressed at
      the prototissue/multicellular level, and that this "multicellular resistance" can
      be minimized or reversed by the appropriate use of so-called "anti-adhesive"
      agents. RESULTS/BACKGROUND: It is well known that monolayer cultures of tumor
      cells-including murine breast cancer-are generally much more intrinsically
      chemosensitive than the same cells grown as solid tumors in vivo. However, the
      relative resistance of solid tumors can often be recapitulated in tissue culture
      simply by growth of the tumor cells as three dimensional multicellular spheroids.
      There are cases where this is also true with respect to acquired drug resistance.
      This "multicellular resistance" could be due to such factors as insufficient drug
      penetration, a reduced growth fraction, or a decreased sensitivity to drug
      induced apoptosis mediated by cell-cell interaction survival signals. Can such
      multicellular resistance mechanisms in solid tumors be reversed? With respect to
      this question, we have recently found that the relative intrinsic resistance of
      intact murine EMT-6 mouse mammary carcinoma spheroids can be significantly
      reversed by the anti-adhesive (disaggregating) effects of hyaluronidase.
      Moreover, this novel method of chemosensitization appears to depend on increased
      recruitment of disaggregated cells into the cycling pool, thus rendering them
      more sensitive to a cell cycle dependent drug such as cyclophosphamide. The
      reduced growth fraction observed in spheroids appears to be due to a marked cell
      contact-dependent upregulation of the cyclin dependent kinase inhibitor, p27Kipl.
      FUTURE OBJECTIVE: The overall goal of our current and future research is to
      determine whether solid tumors, including human breast cancer, express intrinsic
      or acquired resistance at the multicellular level to such drugs as taxol or
      cyclophosphamide, and if so, determine whether it can be reversed by the
      chemosensitizing effect of anti-adhesive agents. This will require a search for
      effective anti-adhesive agents for human cancers as hyaluronidase has not been
      found to possess anti-adhesive function against such tumors to date. In addition,
      the counter-intuitive and innovative idea of downregulating p27kipl in human
      breast cancers as a means of cytotoxic drug chemosensitization is also being
      evaluated.

PMID- 9183657
TI  - Gene therapy: targeting tumor cells for destruction.
AB  - Human gene therapy involves the transfer of genetic material into cells of a
      patient, either in vitro or in situ, for the therapeutic purpose of correcting or
      ameliorating genetic defects, alleviating disease, inhibiting infectious agents
      or destroying cancer cells. After identification of an appropriate disease target
      (inherited or acquired) for treatment, a number of basic technical issues
      underlie any gene therapy strategy. These include the choice of genetic material
      to be transferred, target cell or organ for gene modification, delivery systems
      and representative animal models of the targeted human disease. Tumor gene
      therapy represents a somewhat special category for gene therapy because its
      intended goal is the destruction of tissue rather than its correction or
      preservation. For an experimental therapeutic, cancer represents a useful target
      due to the paucity of effective treatments and the terminal nature of the
      disease. Viral vectors, currently the most widely used agents for gene delivery,
      generally fall into two classes; defective, which are unable to replicate; and
      replication-competent, which are able to replicate and spread within defined cell
      types. The strategies employed for cancer gene therapy range from cytotoxicity,
      either direct or through a 'suicide' gene-producing, to induction of a host
      antitumor immune response. Gene therapy is rapidly moving into the clinic, yet
      its efficacy remains to be demonstrated. Research into the underlying
      fundamentals of gene therapy discussed in this review will be critical to the
      ultimate success of this therapeutic modality.

PMID- 9183658
TI  - [Embryonic induction and role of activins during early amphibian development].
AB  - Growth factors are known to act for the formation of the animal tissues and
      organs. We showed that activins, members of the TGF-beta family growth factors,
      exist in early amphibian embryos and induce mesoderm tissues and organs in
      undifferentiated blastomeres (animal cap). Activins are characteristic in that
      they can establish embryonic body axis, by inducing different mesoderm and
      endoderm organs depending on their dose. The action of activin seems to be a
      primary important phenomenon which commonly create the body pattern of vertebrate
      embryos.

PMID- 9183659
TI  - Telomerase in hepatocellular carcinogenesis.
AB  - Despite the recent advances in diagnostic techniques of HCC, diagnosis of HCC is
      still difficult and ambiguous when HCC is small and of the well differentiated
      type. The results presented here demonstrated that strong telomerase activity was
      frequently detected in HCC irrespective of the stage or size of the nodules but
      neither in non-tumor diseased liver nor in normal liver. Telomerase activity
      determination can be a useful additional tool for the diagnosis of early well
      differentiated HCC.

PMID- 9183660
TI  - [Telomere and telomerase].
AB  - Telomeres are the functional domains positioned at the ends of chromosomes. It is
      essential for the stable maintenance of chromosomes. Telomerase is an enzyme that
      has an important role in the DNA replicator at telomeres. Its activity is
      specifically activated in cancer cells. We have reported a novel specific and
      sensitive assay (stretch RCR assay) for the detection of telomerase activity. We
      analyzed the telomerase activity in leukemias using this method. The results
      showed that telomerase is specifically activated during the progression stages of
      leukemia. The "telomere crisis model" has been proposed for explaining the role
      of the telomere dynamics in malignancies.

PMID- 9183661
TI  - Technical improvement in determining telomerase activity in hematologic
      neoplasias: a possibility of single cell determination of telomerase activity.
AB  - Chromosome termini, telomeres, provide important protective structure to avoid
      loss of master gene(s) that may present at subtelomeric regions. Since the
      telomere length might reflect the cell division, some biological aspects,
      including cellular senescence and cancer biology, of telomere length have been
      reported. To maintain a telomere length related to cell immortality, reactivation
      of telomerase in cancer cells is observed in approximately 85% of more than 1500
      samples obtained from primary cancer tissues. Thus, telomerase is considered to
      be a new marker of neoplasias. In this paper, we present new techniques,
      including fluorescent TRAP that makes it possible to detect telomerase activity
      semi-quantitatively and in situ TRAP assay that allows us to determine the exact
      telomerase-positive cells.

PMID- 9183662
TI  - Genetic regulation of telomerase in a multiple pathways model to cellular
      senescence.
AB  - Hybrids between immortal cells and normal cells senesce, indicating that immortal
      cells have lost, mutated or inactivated genes that are required for the program
      of senescence in normal cells. Genes involved in the senescence program have been
      mapped to over 10 different genetic loci by introduction of normal human
      chromosomes via microcell fusion. Multiple pathways of cellular senescence have
      also been demonstrated by chromosome transfer, indicating that the functions of
      the mapped senescence genes are probably different. One possibility is that one
      or more of these senescence genes may suppress telomerase activity in immortal
      cells, resulting in telomere shortening and cellular senescence. To test this
      hypothesis, telomerase activity and the length of terminal restriction fragments
      (TRFs) have been examined in microcell hybrids. The loss of indefinite growth
      potential was either with or without the loss of telomerase activity activity and
      shortening of telomeres in the microcell hybrids containing the introduced
      chromosome. The findings suggest that telomerase regulation is one of multiple
      pathways to cellular senescence.

PMID- 9183663
TI  - Use of human leukemia-lymphoma cell lines in hematological research: effects of
      thrombopoietin on human leukemia cell lines.
AB  - Normal and malignant hematopoiesis (including megakaryocytopoiesis and
      thrombopoiesis) is regulated by a family of glycoproteins, the hematopoietic
      growth factors (cytokines). The identification of the orphan cytokine receptor
      MPL led to the cloning of the primary regulator of platelet production, termed
      thrombopoietin (TPO). TPO promotes both the proliferation of megakaryocytic
      progenitor cells and their differentiation into platelet-producing
      megakaryocytes. Expression and function of this new cytokine ligand-receptor pair
      were also examined in primary and cultured leukemia cells. Among the large panel
      of human leukemia cell lines studied, MPL expression occurred predominantly in
      lines with erythro-megakaryocytic phenotypes. The MPL receptor was also found in
      a large percentage of primary acute myeloid leukemia (AML) cases. MPL expression
      was not limited to certain morphological subtypes, although the highest
      percentages were seen in the erythroid and megakaryocytic subclasses. A
      significant portion of AML cases and of erythroid, megakaryocytic and myeloid
      leukemia cell lines co-expressed TPO and MPL and mRNA transcripts, although no
      biologically active TPO appeared to be secreted by these cells. Recombinant TPO
      induced clearly in vitro proliferation of a significant percentage of primary AML
      cases, predominantly of the megakaryocytic subtype. TPO significantly enhanced
      the cytokine-induced growth of AML cells in a substantial fraction of cases
      responsive to GM-CSF, IL-3, or SCF. While none of 30 growth factor-independent
      erythro-megakaryocytic leukemia cell lines responded to TPO with increased
      proliferation, TPO strongly augmented the growth of several constitutively
      cytokine-dependent cell lines (HU-3, M-07e, M-MOK, OCI-AML-1, TF-1) which can be
      made TPO-dependent and used as bioassays. Neither in primary cells nor in cell
      lines did TPO appear to induce morphological, functional or immunological
      differentiation. Expression of the MPL receptor is not correlated with a
      proliferative response to TPO. The data reviewed here document the wide
      expression of the MPL receptor on myeloid leukemia cells and also suggest some
      proliferative effects on certain leukemia cells, apparently on non-megakaryocytic
      leukemia cells as well TPO-responsive cell lines represent powerful tools for
      further (patho-)physiological analyses.

PMID- 9183664
TI  - Human B-cell progenitors and bone marrow microenvironment.
AB  - Apoptosis of normal and leukemic immature B-cells in vitro is suppressed by
      contact with bone marrow-derived stromal layers. In stroma-supported cultures of
      immature B-cells, we found that ligation of CD38, a type II transmembrane
      protein, inhibited the cell growth and induced apoptosis. CD38 ligation also
      induced tyrosine phosphorylation and activation of intracellular substrates,
      including syk, phospholipase C-gamma, c-cbl, and phosphatidylinositol 3-kinase
      (PI 3-K). Wortmannin and LY294002, two potent inhibitors of PI 3K, rescued
      immature B cells from CD38-mediated growth suppression. In vitro culture of
      leukemic lymphoblasts may have potentially important clinical application. First,
      stroma-supported cultures of acute lymphoblastic leukemia (ALL) cells can
      determine the growth potential of leukemic cells. In a series of 70 children
      enrolled in a single program of chemotherapy, cell growth on stroma was a
      powerful and independent prognostic indicator. Second, a culture system capable
      of maintaining the majority of ALL blast cells at high levels of viability is
      also ideally suited for testing antileukemic drugs. Promising results were
      obtained with 2-chloro-deoxyadenosine and interleukin-4, leading to clinical
      trials of these two compounds in children with refractory ALL. In addition, we
      compared the direct antileukemic activities of dexamethasone and prednisolone and
      found that dexamethasone is five to six times more cytotoxic (on a molar basis)
      than prednisolone, in agreement with the anti-inflammatory activities of these
      drugs. This finding may serve to guide the selection of dexamethasone dosage in
      the treatment of ALL.

PMID- 9183665
TI  - Abnormal expression of Evi-1 gene in human leukemias.
AB  - The human Evi-1 gene located on chromosome 3q26, encodes a zinc finger protein
      that functions as a transcription factor. It was frequently overexpressed in
      leukemias having 3q26 abnormalities such as t(3;3)(q21;q26) and inv(3)(q21 q26),
      and subjected to structural alteration in t(3;21)(q26;q22). In addition, recent
      studies indicated that several cases of leukemias without 3q26 abnormalities also
      expressed Evi-1 gene. In this study we present another case of structural
      alteration of Evi-1 gene in a case of inv(3)(q21 q26), in which Evi-1 was
      truncated and a shorter form of Evi-1 protein was expressed upon rearrangement of
      the gene. We also studied expression of the Evi-1 gene in a variety of leukemias
      by northern blot analysis. Evi-1 was overexpressed not only in leukemias with
      3q26 abnormalities, but, in those without 3q26 abnormalities, especially in blast
      crisis of CML. Our result also supports an idea that Evi-1 is a relevant oncogene
      whose overexpression or structural changes might play a crucial role in
      development of human leukemias.

PMID- 9183666
TI  - A coiled-coil tetramerization domain of BCR-ABL is essential for the interactions
      of SH2-containing signal transduction molecules.
AB  - BCR-ABL is a chimeric oncoprotein that exhibits deregulated tyrosine kinase
      activity and is implicated in the pathogenesis of Philadelphia chromosome (ph1)
      positive leukemia. We have previously shown SH2-containing phosphotyrosine
      phosphatase SHP-2 forms stable complexes with BCR-ABL and Grb2 in BCR-ABL
      transformed cells (T., Tauchi, et al. J. Biol. Chem. 269, 15381, 1994). To
      elucidate the structural requirement of BCR-ABL for the interactions with SH2
      containing signaling molecules, we examined a series of BCR-ABL mutants which
      include the Grb2 binding site deleted BCR-ABL (1-63 BCR/ABL), the tetramerization
      domain deleted BCR-ABL (64-509 BCR/ABL), and the SH2 domain deleted BCR-ABL
      (BCR/ABL delta SH2). These BCR-ABL mutants were previously shown to reduce the
      transforming activity in fibroblasts. We found that the tetramerization domain
      deleted BCR-ABL did not induce the tyrosine phosphorylation of SHP-2 and the
      interactions of BCR-ABL, SHP-2, and Grb2. In vitro kinase assays have also shown
      the tetramerization domain deleted BCR-ABL mutant did not phosphorylate GST-SHP-2
      in vitro. SHP-2 was co-immunoprecipitated with P13Kinase in BCR/ABL p210
      transformed cells, however this interaction was not observed in the
      tetramerization domain deleted BCR-ABL mutant. Therefore the tetramerization
      domain of BCR-ABL is essential for interactions of these downstream molecules.

PMID- 9183667
TI  - Diverse properties of human t(8;14) neoplasms: [1] ATLS and absence of BCL-2 [2]
      modulation of RAG-1 expression with S-Ig ligation.
AB  - An EBV(-) BL (Burkitt lymphoma) line (Black93), established from a patient
      exhibiting glucocorticoid-induced ATLS (acute tumor lysis syndrome), was highly
      sensitive to dexamethazone (DX) in vitro in the studies including 18 lymphoid
      cell lines (10 BL lines). In the BL lines, the highly sensitive ones always
      lacked Bcl-2(bcl-2 protein), while the DX resistant ones expressed Bcl-2. Black93
      is the first BL cell-line derived from a ATLS patient, proving that cell lines
      can be established in vitro from ATLS patients. Since some pre-B ALL lines
      expressing Bcl-2 were DX-sensitive, the relationship between Bcl-2 and DX
      sensitivity is not straight-forward. In the BL cells, however, the absence of Bcl
      2 appears to be responsible for the DX-sensitivity. The DX-sensitivity and the
      absence of Bcl-2 is a major characteristic carried by t(8;14) neoplasms. In
      addition, there may be a stage of B-lineage differentiation without Bcl-2. While
      rare BL cases have been reported to express TdT (terminal desoxynucleotidyl
      transferase), Tree92 is the first such line, expressing S-Ig(mu, lambda), TdT and
      RAG (recombination activating gene)-1. When surface mu is ligated with antibody,
      RAG-1 was suppressed in expression, indicating that the signal through S-Ig can
      modulate the expression of RAG-1 in the Tree92 cells. Chromosome translocation is
      known to be associated with a specific stage of differentiation. Such specific
      stage for t(8;14), however, is broad enough to cover S-Ig(+), TdT(+) and RAG-1(+)
      stage, too. The phenotypic classification of leukemia/lymphoma and the
      delineation of differentiation scheme of normal hematopoietic cells, are
      dependent on each other. The documentation of the properties such as DX
      sensitivity, the absence of Bcl-2, the expression of RAG-1 and its modulation by
      the signal through S-Ig is an example in which the diverse properties of human
      t(8;14) neoplasms can contribute for delineating the differentiation scheme of
      normal hematopoietic cells more precisely.

PMID- 9183668
TI  - [Establishment of a new human ovarian serous cystadenocarcinoma cell line (IM),
      and influence on cell proliferations by cisplatin with or without hyperthermia].
AB  - A new cell line, designated IM has been established from operation material
      derived from a woman with ovarian serous cystadenocarcinoma. The population
      doubling time of the 35th passage IM cell was 28.8 hours. And it was successively
      subcultured 165 times in over 7 years, moreover still kept CA125 production. The
      nuclear DNA and cell surface CA125 antigen were double stained by propidium
      iodide and anti CA125 monoclonal antibody-FITC. Then the two color cytogram
      obtained by flow cytometry was drawn up. For the most part of CA125 positive cell
      retained G0 + G1 of cell cycle, the lesser part was in G2 + M phase. The S phase
      rate of IM cell incubated with cisplatin at 37 degrees C or 41 degrees C for 1
      hour that estimated by BrdU-propidium iodide double stain method of flow
      cytometry, it was suggested that the inhibition of DNA synthesis by cisplatin was
      increased with 41 degrees C low hyperthermia.

PMID- 9183670
TI  - A possibility of all mRNA expression in a human single lymphocyte.
AB  - Expression of gene transcripts for 16 proteins was investigated in a human single
      lymphocyte using RT-nested PCR method. Examined mRNAs were for IL-2, CD8,
      progesterone receptor, parathyroid hormone, gastrin, glucagon,
      cholecystokinin/pancreozymin, insulin, enkephalin, thyroid stimulating hormone,
      MUC1, MAGE1, pregnancy-specific beta-1 glycoprotein 4, phenylethanolamine-N
      methyltransferase, beta B3-crystallin and HOX4A. Most of the proteins were
      thought to be functionally irrelevant to a lymphocyte. All of them were detected
      in a lymphocyte without exception. The result suggests that there is a
      possibility of all mRNA expression in a human single cell.

PMID- 9183669
TI  - Changes in the ultrastructure of human cells related to certain biological
      responses under hyperthermic culture conditions.
AB  - It has been reported that human cancer cells are more sensitive to high
      temperatures than normal human cells, and that cell proliferation and viability
      are affected by the temperature environment. In this study, we proceeded further,
      and turning our attention to the close relationship between cell morphology and
      temperature, used two human cancer cell lines and two normal cell strains to
      investigate how intracellular fine structure changes in a high temperature
      environment. The results showed that 1) both of the human cancer cell lines were
      more sensitive to high temperature than the normal human cell strains, and a
      difference between the temperature sensitivity of the human cancer cell lines was
      also confirmed. 2) There is no clear difference between the manner in which
      normal human cells and malignant human cells are affected by hyperthermia. 3)
      Among other cell structures, effects on the membrane system were observed as
      early changes in cell structure. The mitochondria were particularly affected,
      followed by the rER. 4) Changes in the nucleoplasm, as well as the nuclear
      membrane (inner membrane), and then the intranuclear chromatin, etc., were
      observed as late changes. 5) Changes in mitochondria were observed in the early
      stage, but temporarily tended to recover, and were then fatally affected again in
      the late stage. We discuss the relationship between cell proliferation, cell
      viability, and cell ultrastructure based on the above results.

PMID- 9183671
TI  - Methylmercury modulation of monocyte chemotactic protein-1 mRNA expression in
      human peripheral blood mononuclear cells.
AB  - The effect of methylmercury (MeHg; CH3HgCl) on the gene expression of monocyte
      chemotactic protein-1 (MCP-1) by human peripheral blood mononuclear cells (PBMC)
      was examined. PBMC were exposed with or without thrombin (1 U/ml) or MeHg (0.3 or
      3.0 microM) for 24 hours. The total RNA was reverse transcribed and then
      amplified by the method of reverse transcriptase-polymerase chain reaction (RT
      PCR). Thrombin enhanced MCP-1 mRNA expression in PBMC. MeHg inhibited thrombin
      stimulated MCP-1 mRNA expression in a dose dependent manner. These findings
      suggest that MeHg affects the atherosclerotic process by changing MCP-1 mRNA
      expression in PBMC.

PMID- 9183672
TI  - Unilateral eye enucleation in adult rats causes neuronal loss in the
      contralateral superior colliculus.
AB  - Several studies have reported the morphological changes induced by unilateral
      enucleation during early neonatal life on the developing visual system. This
      study has examined cellular changes in the superior colliculi by removal of a
      single eye in adult rats. Anaesthetised male hooded rats aged 90 d had their
      right eyes removed. Groups of nonenucleated control and enucleated rats were
      killed when aged either 150 or 390 d. The brains were removed and both the right
      and left superior colliculi dissected out. The volume of the stratum griseum
      superficiale (SGS) within these colliculi was estimated stereologically by light
      microscopy, as well as the numerical density and total number of neurons within
      this cell layer. The volume of the cell layer was reduced by about 40% on the
      side contralateral to the enucleated eye but not on the ipsilateral side at both
      survival periods examined. The numerical density of neurons within the SGS was
      unaffected by the enucleation so that the colliculi contralateral to the
      enucleated eye showed a substantial loss of neurons within this cells layer. This
      study demonstrates the importance of the retinal ganglion cell input, even in
      adult animals, for maintaining the viability of neurons in the SGS layer of the
      superior colliculus.

PMID- 9183673
TI  - The role of maternally derived epidermal growth factor and the epidermal growth
      factor receptor during organogenesis in the rat embryo.
AB  - Epidermal growth factor (EGF) has been implicated in the control of embryonic
      development, but although the receptor is expressed from an early stage, there is
      little evidence of embryonic expression of EGF. In order to investigate the role
      of maternally derived EGF during organogenesis, rat embryos were explanted at d
      9.5 and cultured in serum depleted of low molecular weight molecules (retenate)
      which was then supplemented with EGF. Serum depleted of low molecular weight
      molecules by prolonged filtration loses its capacity to support normal embryonic
      development, possibly due to the loss of growth promoting factors. The addition
      of EGF to retenate significantly improved embryonic development with a maximal
      effect at 8 ng/ml. The addition of an analogue of EGF, long EGF, to retenate also
      caused a significant increase in development, although at higher concentrations a
      decrease in its effect was observed, possibly due to down regulation of the EGF
      receptor. Therefore, embryos may be able to utilise maternally derived EGF during
      organogenesis. To test the effects of inhibiting the EGF receptor during
      organogenesis, d 9.5 embryos were cultured in the presence of tyrphostin 47, a
      specific EGF receptor inhibitor. Tyrphostin 47 caused a significant dose
      dependent decrease in the development of embryos which was also observed when
      tyrphostin 47 was injected into the vitelline circulation at d 11.5 to bypass the
      effects of the yolk sac. These findings suggest that the EGF receptor is
      essential for normal organogenesis and may play a role in the control of
      proliferation and differentiation. Although EGF is not expressed in the rat
      embryo at this stage, maternally derived EGF may be the ligand for the embryonic
      EGF receptor.

PMID- 9183674
TI  - Muscle fibre size and type distribution in thoracic and lumbar regions of erector
      spinae in healthy subjects without low back pain: normal values and sex
      differences.
AB  - This study sought to investigate the normal muscle fibre size and type
      distribution of the human erector spinae, both in thoracic and lumbar regions, in
      a group of 31 young healthy male (n = 17) and female (n = 14) volunteers. Two
      percutaneous muscle biopsy samples were obtained under local anaesthesia, from
      the belly of the left erector spinae, at the levels of the 10th thoracic and 3rd
      lumbar vertebrae. Samples were prepared for routine histochemistry for the
      identification of fibre types. Fibre size (cross-sectional area (CSA) and narrow
      diameter (ND)) was quantified using computerised image analysis. The mean CSA/ND
      for each fibre type was greater in the thoracic than the lumbar region, but there
      was no difference between the 2 regions either for percentage type I (i.e.
      percentage distribution by number), percentage type I area (i.e. relative area of
      the muscle occupied by type I fibres) or the ratio describing the size of the
      type I fibre relative to that of the type II. Men had larger fibres than women,
      for each fibre type and at both sampling sites. In the men, each fibre type was
      of a similar mean size, whereas in the women the type I fibres were considerably
      larger than both the type IIA and type IIB fibres, with no difference between the
      latter two. In both regions of the erector spinae there was no difference between
      men and women for the proportion (%) of a given fibre type, but the percentage
      type I fibre area was significantly higher in the women. The erector spinae
      display muscle fibre characteristics which are clearly very different from those
      of other skeletal muscles, and which, with their predominance of relatively large
      type I (slow twitch) fibres, befit their function as postural muscles.
      Differences between thoracic and lumbar fascicles of the muscle, and between the
      muscles of men and women, may reflect adaptive responses to differences in
      function. In assessing the degree of any pathological change in the muscle of
      patients with low back pain, it seems clear that (1) sex cannot be disregarded
      and (2) 'atrophied' (using the criteria from other muscles) type II fibres are
      not necessarily abnormal for the erector spinae, particularly in women.

PMID- 9183675
TI  - Number, distribution and neuropeptide content of rat knee joint afferents.
AB  - Retrograde tracing with Fluoro-Gold was used to identify the complete population
      of knee joint afferents in the lumbar dorsal root ganglia of adult female Wistar
      rats. There was an average of 581 +/- 31 (mean +/- S.D.) afferents supplying each
      joint. These were found distributed from L1 to L5 with the great majority
      localised in the L3 and L4 ganglia. Electron microscopy of the posterior
      articular nerve of the knee revealed an average of 103 +/- 15 (mean +/- S.D.)
      myelinated and 513 +/- 39 unmyelinated axonal profiles. Since about 50-60% of the
      unmyelinated profiles would be expected to be sympathetic efferents, these
      numbers are consistent with the numbers of afferents found by Fluoro-Gold
      retrograde tracing and suggest that the posterior articular nerve contains about
      50% of the total number of knee joint afferents in the rat. Immunohistochemistry
      revealed that an average of 10% of identified joint afferents expressed substance
      P-like immunoreactivity and that 33% expressed calcitonin gene-related peptide
      like immunoreactivity.

PMID- 9183676
TI  - Structural colocalisation of type VI collagen and fibronectin in agarose cultured
      chondrocytes and isolated chondrons extracted from adult canine tibial cartilage.
AB  - Cell-matrix and matrix-matrix interactions are of critical importance in
      regulating the development, maintenance and repair of articular cartilage. In
      this study, we examined the structural colocalisation of type VI collagen and
      fibronectin in isolated chondrons and long-term agarose cultured chondrocytes
      extracted from normal adult canine articular cartilage. Using double labelling
      immunohistochemistry in conjunction with dual channel confocal microscopy and
      digital image processing we demonstrate that type VI collagen and fibronectin are
      distributed in a similar staining pattern and are colocalised at the surface of
      cultured chondrocytes and isolated chondrons. The results suggest that type VI
      collagen and fibronectin may play a role in both cell-matrix adhesion and matrix
      matrix cohesion in the pericellular microenvironment surrounding articular
      cartilage chondrocytes.

PMID- 9183677
TI  - Growth pattern of the maxillary sinus in the Japanese macaque (Macaca fuscata):
      reflections on the structural role of the paranasal sinuses.
AB  - To investigate the claim that the primate paranasal sinuses possess not a
      functional but a structural role associated with the skull architecture (Blaney,
      1990), the relationship between the maxillary sinus and the skull architecture
      was studied ontogenetically in 30 skulls of male and female Japanese macaques
      (Macaca fuscata). Coronal CT scan series and computerised 3-dimensional images
      served to evaluate the maxillary sinus. The definitive hemispherical shape of the
      sinus was already achieved after the completion of the primary dentition. Sinus
      volume increased with a trend indicating positive allometry. When compared with
      an ontogenetic data set of orang-utan (Koppe et al. 1995), however, the growth
      rate of the maxillary sinus of M. fuscata was significantly less. The maxillary
      sinus both of male and female macaques enlarged according to a common growth
      pattern. However, no sexual dimorphism could be established for the maxillary
      sinus size. Although the volume of the right maxillary sinus was normally bigger
      than that of the left side, the results suggested that asymmetry in maxillary
      sinus volume is related neither to skull size nor sex. Whereas a correlation
      analysis showed close relationships between the maxillary sinus volume and
      external cranial dimensions, the partial correlation coefficients revealed that
      these relationships were highly influenced by skull size. Although it cannot be
      ruled out that the paranasal sinuses are to some extent linked to the skull
      architecture, this study does not support a solely structural role for these air
      cavities.

PMID- 9183678
TI  - Scale development in zebrafish (Danio rerio).
AB  - In the course of an extensive comparative, structural and developmental study of
      the cranial and postcranial dermal skeleton (teeth and scales) in osteichthyan
      fishes, we have undertaken investigations on scale development in zebrafish
      (Danio (Brachydanio) rerio) using alizarin red staining, and light and
      transmission electron microscopy. The main goal was to know whether zebrafish
      scales can be used as a model for further research on the processes controlling
      the development of the dermal skeleton in general, especially epithelial
      mesenchymal interactions. Growth series of laboratory bred specimens were used to
      study in detail: (1) the relationship of scale appearance with size and age; (2)
      the squamation pattern; and (3) the events taking place in the epidermis and in
      the dermis, before and during scale initiation and formation, with the aim of
      searching for morphological indications of epithelial-mesenchymal interactions.
      Scales form late in ontogeny, generally when zebrafish are more than 8.0 mm in
      standard length. Within a population of zebrafish of the same age scale
      appearance is related to standard length, but when comparing populations of
      different age the size of the fish at scale appearance is also related to age.
      Scales always appear first in the posterior region of the body and the squamation
      then extends anteriorly. Scales develop in the dermis but closely apposed to the
      epidermal-dermal boundary. Cellular modifications occurring in the basal layer of
      the epidermis and in the dermis before scale formation clearly indicate that the
      basal epidermal cells differentiate first, before any evidence of differentiation
      of the progenitors of the scale-forming cells in the dermis. This strongly
      suggests that scale differentiation could be initiated by the epidermal basal
      layer cells which probably produce a molecular signal towards the dermis below.
      Subsequently dermal cells accumulate close to the epidermis, and differentiate to
      form scale papillae. The late formation of the scales during ontogeny is due to a
      late colonisation of the dermis by the progenitors of the scale-forming cells.
      Because of their late formation during ontogeny and of their regular pattern of
      development, scales in zebrafish represent a good model for further
      investigations on the general mechanisms of epithelial-mesenchymal interactions
      during dermal skeleton development, and in particular for the study of the gene
      expression patterns.

PMID- 9183679
TI  - Nuclear morphogenesis and the role of the manchette during spermiogenesis in the
      ostrich (Struthio camelus).
AB  - Nuclear condensation during spermiogenesis in the ostrich follows the basic
      pattern established in other vertebrates. The fine granular nuclear substance of
      early spermatids is gradually replaced by numbers of coarse dense granules which
      appear to arise by aggregation of smaller dispersed elements of the chromatin.
      The granules increase in size and eventually coalesce to form the compact
      homogenous mass of chromatin typical of the mature sperm. In ostrich spermatids,
      however, the aggregation of the nuclear material produces large numbers of
      longitudinally oriented rod-shaped structures in addition to some granular
      material. Although fibrillar chromatin has been observed during spermiogenesis in
      a number of vertebrate species, the hollow nature of the rod-shaped chromatin
      granules in ostrich spermatids is a unique phenomenon. The spiralisation of the
      chromatin material observed in ostrich spermatids and in some other nonpasserine
      birds is possibly related to the reduction in nuclear length demonstrated during
      spermiogenesis in these species. In common with other nonpasserine birds,
      spermiogenesis in the ostrich is characterised by the appearance both of a
      circular and a longitudinal manchette. The circular manchette consists of a
      single row of microtubules reinforced by additional peripherally arranged
      microtubules. Links between adjacent microtubules, and between the nucleolemma
      and some of the microtubules, are evident. The longitudinal manchette consists of
      arrays of interconnected microtubules arranged in approximately 4-6 staggered,
      ill defined rows. This structure seems to originate as a result of the
      rearrangement of the microtubules of the circular manchette and is only formed
      once the process of chromatin condensation is well advanced. Based on the
      sequence of morphological events observed during spermiogenesis in the ostrich,
      it is concluded that the circular manchette is responsible for the initial
      transformation in shape of the spermatid nucleus. Thereafter, the chromatin
      condenses independently within the confines of the nucleolemma with the circular
      manchette merely acting to maintain the shape of the nucleus while this process
      is underway, to compress the nuclear membrane, and possibly to orientate the
      subunits of the condensing chromatin. The longitudinal manchette appears to
      assist in the translocation of material during spermatid elongation. There are
      indications that the developing acrosome is instrumental in effecting nuclear
      shaping of the apical (subacrosomal) head region of the ostrich spermatid.

PMID- 9183680
TI  - The effects of pre- and postnatal exposure to the nonsteroidal antiandrogen
      flutamide on testis descent and morphology in the Albino Swiss rat.
AB  - Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide
      during the period from gestational day (d) 10 to birth resulted in feminisation
      of the external genitalia and the suppression of growth of the male reproductive
      tract. In adulthood, testes were found to be located in diverse positions. True
      cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the
      scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees
      of tubule abnormality were seen in the testes of flutamide-treated animals,
      ranging from completely normal tubules with full spermatogenesis (and the
      expected frequency of the stages of spermatogenesis) to severely abnormal tubules
      lined with Sertoli cells only. For each individual testis, the overall severity
      of tubule damage was strongly correlated with its adult location, with intra
      abdominal testes worst affected and scrotally-located testes least; only the
      latter contained normal tubules. Similarly, intra-abdominal testes were the
      smallest in weight and contained the least testosterone. By contrast, postnatal
      treatment of male rats with flutamide from birth to postnatal d 14 did not impair
      development of the external genitalia, the process of testicular descent or adult
      spermatogenesis. These findings confirm that androgen blockade during embryonic
      development interferes with testicular descent but also demonstrate that (1)
      prenatal flutamide treatment per se has a detrimental effect on adult testis
      morphology but (2) the degree of abnormality of the testes is strongly influenced
      by location.

PMID- 9183681
TI  - Fine structure of the cap enameloid and of the dental epithelial cells during
      enameloid mineralisation and early maturation stages in the tilapia, a teleost.
AB  - Morphological features of the cap enameloid and dental epithelial cells were
      investigated by light and transmission electron microscopy during the various
      stages of enameloid mineralisation and early maturation in the tilapia. The
      pattern of mineralisation along collagen fibrils in the enameloid differed from
      that in the dentine. Many matrix vesicles were found in the predentine and in the
      enameloid, suggesting that they may be involved in the initial mineralisation in
      both regions. Most of the organic matrix disappeared from the cap enameloid
      during mineralisation and maturation. The disappearance of the organic matrix
      could be divided into 2 stages. Initially a fine network-like matrix, which
      probably consisted of glycosaminoglycans and extended between collagen fibrils,
      began to disappear. At the same time, fine crystallites and electron-dense, fine
      granular material covered the collagen fibrils as mineralisation of the enameloid
      began. In the second stage, the maturation of the enameloid, the collagen fibrils
      degenerated completely and disappeared from the cap enameloid, being replaced by
      large numbers of large crystals. At the mineralisation stage, the numbers of
      lysosomal bodies tended to increase in the inner dental epithelial (IDE) cells,
      which contained a well developed Golgi apparatus and rough endoplasmic reticulum
      (rER). At the early stage of maturation, a ruffled border was noted at the distal
      ends of the IDE cells, which contained many mitochondria and lysosomal bodies,
      but less rER. These features suggest that the cells actively absorb the organic
      matrix, which includes collagen fibrils, in the cap enameloid. The outer dental
      epithelial (ODE) cells were translucent cells that contained well developed
      labyrinthine canalicular spaces from the onset of the mineralisation stage to the
      middle stage of maturation. The IDE and ODE cells were clearly involved in the
      mineralisation of the cap enameloid at the mineralisation and maturation stages.

PMID- 9183682
TI  - Confocal laser scanning microscopy of porcine skin: implications for human wound
      healing studies.
AB  - The structure of porcine skin as examined by light microscopy is reviewed and its
      similarities to and differences from human skin are highlighted. Special imaging
      techniques and staining procedures are described and their use in gathering
      morphological information in porcine skin is discussed. Confocal laser scanning
      microscopy (CLSM) was employed to examine the structure of porcine skin and the
      findings are presented as an adjunct to the information already available in the
      literature. It is concluded that CLSM provides valuable additional morphological
      information to material examined by conventional microscopy and is useful for
      wound healing studies in the porcine model.

PMID- 9183684
TI  - Possums, articular cartilage and oxygen. A comment on the papers by Archer et al.
      (1996) and Morrison et al. (1996)

PMID- 9183683
TI  - Changes in muscle fibre type, muscle mass and IGF-I gene expression in rabbit
      skeletal muscle subjected to stretch.
AB  - The relationship between IGF-1 and changes in muscle fibre phenotype in response
      to 6 d of stretch or disuse of the lower limb muscles of the rabbit was studied
      by combining in situ hybridisation and immunohistochemistry procedures. Passive
      stretch by plaster cast immobilisation of the muscle in its lengthened position
      not only induced an increase in IGF-I mRNA expression within the individual
      muscle fibres but also an increase in the percentage of fibres expressing
      neonatal and slow myosin. This change in phenotype was also found to be
      accompanied by a rapid and marked increase of muscle mass, total RNA content as
      well as IGF-I gene expression. In contrast, IGF-I appears not to be involved in
      muscle atrophy induced by immobilisation in the shortened position and the
      inactivity which results from this procedure. The level of increase in expression
      of IGF-I mRNA varied from fibre to fibre. By using adjacent serial sections, the
      fibres which expressed IGF-I mRNA at the highest levels were identified as
      expressing neonatal and the slow type 1 myosin. These data suggest that the
      expression of IGF-I within individual muscle fibres is correlated not only with
      hypertrophy but also with the muscle phenotypic adaptation that results from
      stretch and overload.

PMID- 9183685
TI  - Immunohistochemical localization of neurocan and L1 in the formation of
      thalamocortical pathway of developing rats.
AB  - We used immunohistochemistry to examine possible molecular interactions between
      the subplate and growing thalamocortical axons in rat fetuses. In the cortical
      anlage of embryonic day 16 (E16), the subplate first appeared below the cortical
      plate. Among chondroitin sulfate proteoglycans, phosphacan was uniformly
      distributed throughout the cortical wall, whereas neurocan was localized only in
      the subplate at E16. Neural cell adhesion molecules, NCAM-H, TAG-1, and L1, were
      detected in the cortical anlage. Both cortical neurons and growing axons were
      diffusely immunopositive for NCAM-H, and TAG-1 immunoreactivity was found on
      immature neurons and cortical efferent axons but not on thalamocortical axons. L1
      immunoreactivity was specifically localized on the growing thalamocortical axons.
      When the locations of neurocan and L1 were compared in the developing cortex, L1
      bearing axons were found to extend to neurocan-immunopositive regions; neurocan
      immunoreactivity was intense in the subplate at E16, when small numbers of L1
      immunoreactive thalamocortical axons began to invade the cortex. At E17, many L1
      positive axons were observed in the subplate that expressed neurocan
      specifically. Double immunostaining showed that L1-positive axons and neurocan
      immunoreactivity overlapped in the subplate at E17. After E18, neurocan
      expression gradually extended to the lower part of the cortical plate; it
      extended to the entire cortex by E21, 1 day before birth. By E21, L1-bearing
      axons had invaded the lower part of the cortical plate. The present study
      demonstrated that the neurocan expression precedes growth of L1-bearing
      thalamocortical afferent fibers. Because neurocan can bind to L1 molecule in
      vitro, these results suggest that neurocan and L1 play some important roles in
      pathfinding of the thalamocortical afferent fibers during rat corticogenesis.

PMID- 9183686
TI  - Cortical, thalamic, and amygdaloid projections of rat temporal cortex.
AB  - The cortical, thalamic, and amygdaloid connections of the rodent temporal
      cortices were investigated by using the anterograde transport of
      iontophoretically injected biocytin. Injections into area Te1 labeled axons and
      terminals in the ventral regions of the dorsal and ventral subnuclei of the
      medial geniculate complex, area Te3, the rostrodorsal part of area Te2, and the
      ventrocaudal caudate putamen. No amygdaloid labeling was observed. Thalamic
      projections from Te2 targeted the lateral posterior nucleus, the dorsal part of
      the dorsal subnucleus of the medial geniculate complex, and the peripeduncular
      nucleus. Corticocortical projections mainly terminated in the dorsal perirhinal
      cortex, but moderately dense projections were observed in medial and lateral
      peristriate cortex, and only light projections were observed to Te1 and Te3.
      Projections to these isocortical regions terminated in layers I and VI.
      Amygdaloid projections targeted the ventromedial subdivision of the lateral
      nucleus and the adjacent part of the anterior basolateral nucleus. Area Te3 was
      observed to project to the ventrolateral parts of the dorsal and ventral
      subnuclei of the medial geniculate complex, the dorsal perirhinal cortex, rostral
      Te2, and Te1. In the amygdala, labeled fibers and terminals were concentrated in
      the dorsolateral subdivision of the lateral nucleus. These data confirm that
      areas Te1 and Te3 are hierarchically organized cortical areas connected with
      auditory relay nuclei in the thalamus. Area Te2, in contrast, appears to be
      weakly connected with Te1 and Te3 but is heavily connected with the peristriate
      cortex and tectorecipient thalamic nuclei. Te2 appears to be a visually related
      cortical area. The data also indicate that projections from Te2 and Te3 target
      different subregions of the lateral nucleus and that Te2, but not Te3, projects
      to the basolateral nucleus.

PMID- 9183687
TI  - Serotonin-immunoreactivity in peripheral tissues of the opisthobranch molluscs
      Pleurobranchaea californica and Tritonia diomedea.
AB  - The distribution of serotonin (5-HT)-immunoreactive elements in peripheral organs
      of the sea-slugs Pleurobranchaea californica and Tritonia diomedea was studied in
      cryostat sections. For Pleurobranchaea, 5-HT-immunoreactive (5-HT-IR) neuron cell
      bodies were found only in the central nervous system (CNS); 5-HT-IR cell bodies
      were not observed in foot, tentacles, rhinophores, oral veil, mouth, buccal mass,
      esophagus, gills, salivary glands, skin, reproductive system, and acidic glands,
      nor in peripheral tentacle and rhinophore ganglia. However, 5-HT-IR neuronal
      processes were widely distributed in these structures and the patterns of 5-HT-IR
      elements were characteristic for each particular peripheral tissue. 5-HT-IR
      elements were most dense in the sole of the foot and the reproductive system,
      followed by rhinophores, tentacles, oral veil, mouth, buccal mass, and esophagus.
      The sensory epithelium of rhinophores, tentacles, and mouth showed a highly
      structured glomerular organization of 5-HT-IR fibers, suggesting a role for 5-HT
      in sensory signaling. A much lower density of 5-HT-IR innervation was observed in
      gills, skin, salivary, and acidic glands. 5-HT-IR was observed in neuropil of
      tentacle and rhinophore ganglia with many transverse 5-HT-IR axons running to
      peripheral sensory areas. The distribution of 5-HT-IR elements in Tritonia was
      similar to that of Pleurobranchaea. A significant suggestion of the data is that
      central serotonergic neurons may modulate afferent pathways from sensory
      epithelia at the periphery.

PMID- 9183688
TI  - Expression of fibroblast growth factor-2 in hypoglossal motoneurons is stimulated
      by peripheral nerve injury.
AB  - We have studied the expression of basic fibroblast growth factor 2 (FGF-2) and
      FGF receptor 1 (FGFR1) in the hypoglossal motor system during degeneration and
      regeneration by using an RNase protection assay, in situ hybridization, and
      Western blot analysis. The FGF-2 transcript was found to be weakly expressed in
      the hypoglossal motoneurons of the adult rat. Both peripheral transection and
      crush injury of the hypoglossal nerve resulted in a marked up-regulation of the
      FGF-2 mRNA in motoneurons of the hypoglossal nucleus (with a peak at 10 and 11
      days postlesion) as well as in the proximal and distal nerve stumps. The FGFR1
      transcript was strongly expressed by hypoglossal motoneurons of unlesioned rats.
      Neither axotomy nor crush lesion of the hypoglossal nerve revealed any alteration
      of the expression level and cellular localization in the hypoglossal nucleus, but
      they did result in a significant increase of the FGFR1 mRNA level in the proximal
      and distal nerve stump. Western blot analysis of the hypoglossal nucleus revealed
      the presence of the 21 kD and 23 kD isoforms and of a weak expression of the 18
      kD isoform. Hypoglossal nerve transection resulted in a complete down-regulation
      of the FGF-2 protein 3 days after lesion. After 14 days, however, the level of
      the three isoforms was increased above the control level. The regulation of FGF-2
      in hypoglossal motoneurons after experimental nerve injury is in agreement with
      the idea of a lesion-related function of FGF-2. Together with previously reported
      neurotrophic effects, these results suggest that FGF-2 provides trophic support
      for lesioned motoneurons. At the injury site, FGF-2 could be involved in the
      regulation of the myelination.

PMID- 9183689
TI  - Connexin43 and astrocytic gap junctions in the rat spinal cord after acute
      compression injury.
AB  - To examine the possible role of interastrocytic gap junctions in the maintenance
      of tissue homeostasis after spinal cord damage, we initiated studies of the
      astrocytic gap junctional protein connexin43 (Cx43) in relation to temporal and
      spatial parameters of neuronal loss, reactive gliosis, and white matter survival
      in a rat model of traumatic spinal cord injury (SCI). Cx43 immunolocalization in
      normal and compression-injured spinal cord was compared by using two different
      sequence-specific anti-Cx43 antibodies that have previously exhibited different
      immunorecognition properties at lesion sites in brain. At 1- and 3-day survival
      times, gray matter areas with mild to moderate neuronal depletion exhibited a
      loss of immunolabeling with one of the two antibodies. At the lesion epicenter,
      these areas consisted of a zone that separated normal staining distal to the
      lesion from intensified labeling seen with both antibodies immediately adjacent
      to the lesion. Loss of immunoreactivity with only one of the two antibodies
      suggested masking of the corresponding Cx43 epitope. By 7 days post-SCI, Cx43
      labeling was absent with both antibodies in all regions extending up to 1 mm from
      the lesion site. Reactive astrocytes displaying glial fibrillary acidic protein
      (GFAP) appeared by 1 day and were prominent by 3 days post-SCI. Their
      distribution in white and gray matter corresponded closely to that of Cx43
      staining at 1 day, but less so at 3 days when GFAP-positive profiles were present
      at sites where Cx43 labeling was absent. By 7 days post-SCI, Cx43 again co
      localized with GFAP-positive cells in the surviving subpial rim, and with
      astrocytic processes on radially oriented vascular profiles investing the central
      borders of the lesion. The results indicate that alterations in Cx43 cellular
      localization and Cx43 molecular modifications reflected by epitope masking, which
      were previously correlated with gap junction remodeling following excitotoxin
      induced lesions in brain, are not responses limited to exogenously applied
      excitotoxins; they also occur in damaged spinal cord and are evoked by endogenous
      mechanisms after traumatic SCI. The GFAP/Cx43 co-localization results suggest
      that during their transformation to a reactive state, spinal cord astrocytes
      undergo a transitional phase marked by altered Cx43 localization or expression.

PMID- 9183690
TI  - Simultaneous anterograde labeling of axonal layers from lateral superior olive
      and dorsal cochlear nucleus in the inferior colliculus of cat.
AB  - The laminar organization of the central nucleus of inferior colliculus includes
      layers of axons that may be important in shaping the responses of neurons.
      Depending on their source, some layered axons are afferents that are superimposed
      and terminate on the same postsynaptic neurons, while other layered afferents,
      such as those from the ipsilateral and contralateral lateral superior olive,
      terminate side-by-side. The specific pattern of convergence may dictate which
      populations of axons are presynaptic to layered disc-shaped neurons in the
      central nucleus. We compared the distribution of afferent axons from the dorsal
      cochlear nucleus and the lateral superior olive to the contralateral inferior
      colliculus in the cat. Injection sites in cochlear nucleus and superior olive
      were physiologically characterized by extracellular recordings of single and
      multiple units in response to monaural and binaural acoustic stimulation. Two
      separate injections were made in each case, and both injection sites contained
      units with overlapping best frequencies. Biotinylated dextran, fluorescent
      dextran, 3H-leucine, and wheat germ agglutinin conjugated to horseradish
      peroxidase were used as anterograde tracers. The present results show that
      layered axons from the dorsal cochlear nucleus and lateral superior olive are
      superimposed in part of the contralateral central nucleus. Both projections were
      arranged in rostro-caudally oriented axonal layers that converged in the ventral
      part of the central nucleus. However, in the dorsal part of the central nucleus,
      the same layer of axons from the dorsal cochlear nucleus did not terminate with
      afferents from the lateral superior olive. Within the overlapping layers in the
      ventral central nucleus, the overlap of axons from the dorsal cochlear nucleus
      and the lateral superior olive was uniform except for small patches that were
      usually smaller than the dendritic fields of disc-shaped neurons. These data
      suggest that the layers may create specific functional zones in the central
      nucleus of the inferior colliculus. One zone may contain neurons with binaural
      responses that combine the properties of the inputs from the contralateral
      lateral superior olive and the dorsal cochlear nucleus. A second zone may contain
      inputs from the cochlear nucleus but lack those of the lateral superior olive.

PMID- 9183691
TI  - Neuritic differentiation and synaptogenesis in serum-free neuronal cultures of
      the rat cerebral cortex.
AB  - To better understand the dynamics of the cellular processes involved in early
      neocortical development, we studied the neuritic differentiation and
      synaptogenesis of dispersed neurons grown in serum-free cultures under a wide
      variety of culture conditions. Microtubule-associated protein (MAP2),
      phosphorylated neurofilament (SMI 31) and synaptophysin immunocytochemistry was
      complemented with time-lapse studies. During the first week in vitro dissociated
      cortical neurons developed from roundish cells without processes to neurons with
      axons and differentiated dendrites, going through five distinct phases. The
      sequence of these phases was unaltered in a wide range of culturing methods, but
      the timing of the steps varied among cultures started with different cell
      densities. Synaptic terminals were first observed after 3-4 days in vitro,
      coincident with the beginning of dendritic differentiation. Synaptogenesis
      progressed at least until the end of the third week in vitro, despite a decline
      in cell density during the second week in vitro. The process of cellular
      differentiation of cerebral cortical neurons in vitro resembled the development
      of these cells in the intact tissue, suggesting that organized cell migration is
      not a prerequisite for the differentiation of single cortical neurons.

PMID- 9183692
TI  - Distribution of neuronal apoptosis inhibitory protein-like immunoreactivity in
      the rat central nervous system.
AB  - We have recently shown that spinal muscular atrophy (SMA), an autosomal recessive
      disorder characterized by motor neuron loss, is associated with deletion of a
      gene that encodes the neuronal apoptosis inhibitory protein (NAIP). In the
      present study, we have examined the distribution of NAIP-like immunoreactivity
      (NAIP-LI) in the rat central nervous system (CNS) by using an affinity-purified
      polyclonal antibody against NAIP. In the forebrain, immunoreactive neurons were
      detected in the cortex, the hippocampus (pyramidal cells, dentate granule cells,
      and interneurons), the striatum (cholinergic interneurons), the basal forebrain
      (ventral pallidum, medial septal nucleus, and diagonal band), the thalamus
      (lateral and ventral nuclei), the habenula, the globus pallidus, and the
      entopenduncular nucleus. In the midbrain, NAIP-LI was located primarily within
      neurons of the red nucleus, the substantia nigra pars compacta, the oculomotor
      nucleus, and the trochlear nucleus. In the brainstem, neurons containing NAIP-LI
      were observed in cranial nerve nuclei (trigeminal, facial, vestibular, cochlear,
      vagus, and hypoglossal nerves) and in relay nuclei (pontine, olivary, lateral
      reticular, cuneate, gracile nucleus, and locus coeruleus). In the cerebellum,
      NAIP-LI was found within both Purkinje and nuclear cells (interposed and lateral
      nuclei). Finally, within the spinal cord, NAIP-LI was detected in Clarke's column
      and in motor neurons. Taken together, these results indicate that NAIP-LI is
      distributed broadly in the CNS. However, high levels of NAIP-LI were restricted
      to those neuronal populations that have been reported to degenerate in SMA. This
      anatomical correspondence provides additional evidence for NAIP involvement in
      the neurodegeneration observed in acute SMA.

PMID- 9183693
TI  - Distribution of transferrin binding protein immunoreactivity in the chicken
      central and peripheral nervous systems.
AB  - Transferrin binding protein (TfBP) is a glycoprotein originally purified from
      chicken oviduct that exhibits transferrin binding activity. Recent work has shown
      that TfBP is a post-translationally modified form of the heat shock protein
      (HSP108), the avian homologue of a glucose regulated protein, GRP94. The function
      of this protein, however, has not yet been clearly defined. Antiserum to TfBP was
      found to selectively stain oligodendrocytes of the avian brain. In this study, we
      further describe these oligodendrocytes and other cell types positive to anti
      TfBP in the chick nervous system. In accordance with previous studies, the most
      prominent cell type that labels with antiserum to TfBP is the oligodendrocyte. At
      the electron microscopic level, the immunoreactive product is confined to the
      perinuclear cytoplasm and fine processes of the oligodendrocytes, whereas myelin
      and axoplasm are devoid of staining. The immunoreactive product is found both in
      the cytoplasmic matrix and bound to the endoplasmic reticulum and plasma
      membrane, suggesting that TfBP may have properties of both a soluble and an
      integral membrane protein. There is great variability in the number of TfBP
      oligodendrocytes in different areas of the central nervous system (CNS); large
      numbers of cells are associated with the white matter regions and are found in
      the myelinated tracts, whereas few cells are present in the gray matter regions.
      In the retina, TfBP is localized specifically in the cells, that are
      morphologically oligodendrocytic and is present in the optic nerve fiber layer
      and the ganglion cell layer. Obvious staining is also seen in the Bergmann glial
      cells of the cerebellum and in the Schwann cells of the sciatic nerve.
      Furthermore, the choroid plexus cells similarly exhibit a strong reaction. The
      association of TfBP in these specific cell types responsible for myelination and
      sequestering iron and transferrin implies that TfBP may be involved in
      myelination and iron metabolism of the chick nervous system, perhaps through a
      role in transferrin concentration in these cells. A putative role of TfBP, as
      HSP108, is considered.

PMID- 9183694
TI  - Spatiotemporal coordination of rod and cone photoreceptor differentiation in
      goldfish retina.
AB  - In this study, we have compared spatial and temporal aspects of development of
      new rods and cones in the adult goldfish by using a combination of
      bromodeoxyuridine immunocytochemistry and opsin in situ hybridization to
      determine the intervals between terminal mitosis (cell "birth") and expression of
      opsin mRNA for each photoreceptor cell type. The goldfish opsins include rod
      opsin and four different cone opsins: red, green, blue, and ultraviolet. In a
      cohort of photoreceptors born at the same time, rods expressed opsin mRNA within
      3 days of cell birth, while expression of cone opsin mRNA required at least 7
      days. This temporal discrepancy in differentiation, coupled with a discordance in
      the site of cell genesis of rods and cones, allowed opsin expression to commence
      in both cell types in approximately the same retinal location. Commitment to the
      generic cone phenotype occurred within approximately 6 days throughout the cone
      cohort, as indicated by expression of interphotoreceptor retinoid-binding protein
      (IRBP) mRNA, but expression of a specific spectral phenotype was delayed until
      rods differentiated nearby. Onset of expression of cone opsin mRNA followed a
      phenotype-specific sequence: red, then green, then blue, and finally ultraviolet;
      in situ hybridization with two opsin probes confirmed that individual
      photoreceptors expressed only one type of opsin as they differentiated. This
      stepwise process of cone differentiation is consistent with the hypothesis that
      cell-cell interactions among developing photoreceptors may coordinate selection
      of specific photoreceptor phenotypes.

PMID- 9183695
TI  - Ultrastructural study of cholinergic and noncholinergic neurons in the pars
      compacta of the rat pedunculopontine tegmental nucleus.
AB  - A group of medium-to-large cholinergic neurons situated in the dorsolateral
      mesopontine tegmentum comprises the pedunculopontine tegmental nucleus (PPT). The
      PPT pars compacta (PPT-pc), which occupies the lateral part of the caudal two
      thirds of the nucleus, contains a dense aggregation of cholinergic neurons. In
      the present study, we have employed immunohistochemistry for choline
      acetyltransferase (ChAT) and electron microscopy to investigate the
      ultrastructure and synaptic organization of neuronal elements in the PPT-pc. Our
      results demonstrate that: (1) ChAT-immunoreactive (i.e., cholinergic) PPT-pc
      neurons are characterized by abundant cytoplasm and organelles, and have few
      axosomatic synapses (both asymmetric and symmetric); (2) ChAT-immunoreactive
      dendrites comprise 6-15% of total dendritic elements in the neuropil; the mean
      percentage of dendritic membrane covered by synaptic terminals is approximately
      15%, and nearly all synapses with ChAT-immunoreactive dendrites are asymmetric;
      (3) within the boundaries described by cholinergic PPT-pc, there are
      noncholinergic neurons which, in contrast, exhibit a lucent cytoplasm and a
      higher frequency of axosomatic synapses (10.5% versus 3.7% for cholinergic
      neurons); and (4) noncholinergic neurons are morphologically heterogeneous with
      one subpopulation exhibiting a mean diameter that approximates that of
      cholinergic cells (i.e., > 15 microns and < 20 microns) and a very high frequency
      of axosomatic synapses (> 20%). Only 0.2-0.7% of terminal elements in the
      neuropil were ChAT-immunoreactive and these were not observed to synapse with
      cholinergic dendrites or somata. This relative paucity of terminal labeling and
      lack of cholinergic-cholinergic interactions seems inconsistent with the
      recognized and prominent physiological actions of acetylcholine on cholinergic
      PPT-pc neurons, and suggests a methodological limitation and/or a potential
      paracrine-like action of nonsynaptically released acetylcholine in the PPT
      region.

PMID- 9183696
TI  - Serotonergic dorsal raphe nucleus projections to the cholinergic and
      noncholinergic neurons of the pedunculopontine tegmental region: a light and
      electron microscopic anterograde tracing and immunohistochemical study.
AB  - The serotonergic dorsal raphe nucleus is considered an important modulator of
      state-dependent neural activity via projections to cholinergic neurons of the
      pedunculopontine tegmental nucleus (PPT). Light and electron microscopic analysis
      of anterogradely transported biotinylated dextran, combined with choline
      acetyltransferase (ChAT) immunohistochemistry, were employed to describe the
      synaptic organization of mesopontine projections from the dorsal raphe to the
      PPT. In a separate set of experiments, we utilized immunohistochemistry for the
      serotonin transporter (SERT), combined with ChAT immunohistochemistry at the
      light and electron microscopic levels, to determine whether PPT neurons receive
      serotonergic innervation. The results of these studies indicate that: (1)
      anterogradely labeled and SERT-immunoreactive axons and presumptive boutons
      invest the PPT at the light microscopic level; (2) at the ultrastructural level,
      dorsal raphe terminals in the PPT pars compacta synapse mainly with dendrites and
      axosomatic contacts were not observed; (3) approximately 12% of dorsal raphe
      terminals synapse with ChAT-immunoreactive dendrites; and (4) at least 2-4% of
      the total synaptic input to ChAT-immunoreactive dendrites is of dorsal raphe
      and/or serotonergic origin. This serotonergic dorsal raphe innervation may
      modulate cholinergic PPT neurons during alterations in behavioral state. The role
      of these projections in the initiation of rapid eye movement (REM) sleep and the
      ponto-geniculo-occipital waves that precede and accompany REM sleep is discussed.

PMID- 9183697
TI  - Efferent connections of the internal globus pallidus in the squirrel monkey: I.
      Topography and synaptic organization of the pallidothalamic projection.
AB  - The objectives of this study were, on one hand, to better understand how the
      segregated functional pathways from the cerebral cortex through the
      striatopallidal complex emerged in the projections to the thalamus and, on the
      other hand, to compare the ultrastructure and synaptic organization of the
      pallidal efferents to the ventrolateral (VL) and centromedian (CM) thalamic
      nuclei in primates. These aims were achieved by injections of the retrograde
      anterograde tracer, biotinylated dextran amine (BDA), in different functional
      regions of the internal pallidum (GPi) in squirrel monkeys. The location of
      retrogradely labelled cells in the striatum was determined to ascertain the
      functional specificity of the injection sites. Injections in the ventrolateral
      two-thirds of the GPi (group 1) led to retrograde labelling in the
      postcommissural region of the putamen ("sensorimotor striatum") and plexuses of
      labelled fibers in the rostral one-third of the principal ventrolateral nucleus
      (VLp) and the central part of the CM. On the other hand, injections in the dorsal
      one-third (group 3) and the rostromedial pole (group 4) of the GPi led to
      retrogradely labelled cells in the body of the caudate nucleus ("associative
      striatum") and the ventral striatum ("limbic striatum"), respectively. After
      those injections, dense plexuses of anterogradely labelled varicosities were
      found in common thalamic nuclei, including the parvocellular ventral anterior
      nucleus (VApc), the dorsal VL (VLd), and the rostrodorsal part of the
      parafascicular nucleus (PF). In the caudal two-thirds of the CM/PF, the labelled
      fibers formed a band that lay along the dorsal border of the complex in a region
      called the dorsolateral PF (PFdl) in this study. The ventromedial nucleus (VM)
      was densely labelled only after injections in the rostromedial GPi, whereas the
      dorsal part of the zona incerta was labelled in both groups. At the electron
      microscopic level, the BDA-positive terminals in the VLp were larger and more
      elongated than those in the CM but, overall, displayed the same pattern of
      synaptic organization. Our findings indicate 1) that some associative and limbic
      cortical information, which is largely processed in segregated
      corticostriatopallidal channels, converges to common thalamic nuclei and 2) that
      the PF is a major target of associative and limbic GPi efferents in monkeys.

PMID- 9183698
TI  - Efferent connections of the internal globus pallidus in the squirrel monkey: II.
      Topography and synaptic organization of pallidal efferents to the
      pedunculopontine nucleus.
AB  - The first objective of the present study was to verify whether projections from
      regions of the internal pallidum (GPi) that receive inputs from different
      functional areas of the striatum remain segregated at the level of the
      pedunculopontine nucleus (PPN) in squirrel monkeys. Second, we analyzed the
      ultrastructural features and synaptic organization of pallidal terminals in
      contact with PPN neurons. This was achieved by performing iontophoretic
      injections of biotinylated dextran amine (BDA) in different regions of the GPi.
      The animals were pooled into three groups on the basis of the location of the
      injection sites and the resulting distribution of retrogradely labelled striatal
      neurons. The experimental groups were divided as follows: group 1: injections in
      the dorsal one-third of the GPi, retrograde labelling in the head and body of the
      caudate nucleus ("associative striatum"); group 2: injections in the
      ventrolateral two-thirds of the GPi, retrograde labelling in the postcommissural
      region of the putamen ("sensorimotor striatum"); and group 3: injections in the
      rostromedial pole of the GPi, retrograde labelling in the ventral striatum
      ("limbic striatum"). These injections led to the anterograde labelling of
      varicose fibers that arborized profusely in common regions of the PPN dorsal to
      the brachium conjunctivum. The fields of fibers that arose from the dorsal one
      third and the rostromedial pole of the GPi were more widely spread than the
      afferents from the ventrolateral two-thirds of the GPi. Small numbers of
      retrogradely labelled cells were encountered in the PPN after each injection in
      the GPi. Some of them were tightly surrounded by large, BDA-containing
      varicosities, which implies that the connections between the GPi and the PPN are
      partly reciprocal. In sections processed for the simultaneous localization of
      beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (a marker of
      cholinergic cells in the PPN) and BDA, the anterogradely labelled fibers largely
      avoided the dense aggregate of NADPH-diaphorase-containing neurons in the PPN
      pars compacta (PPNc) but, rather, established contacts with unlabelled neurons in
      the pars dissipata (PPNd). In the electron microscope, the GPi terminals were
      large (1.0-5.0 microns in diameter), contained many mitochondria and pleomorphic
      vesicles, and formed symmetric synapses predominantly with proximal dendrites of
      PPN cells. In conclusion, our data suggest that the noncholinergic neurons of the
      PPNd are potential targets for the integration of information arising from
      different functional territories of the GPi in primates. The PPNd is thus in a
      position to act as an interface between motivational, cognitive, and motor
      information transmitted along the pallidotegmental projection in primates.

PMID- 9183699
TI  - Axonal connections of the medial magnocellular nucleus of the anterior
      neostriatum in zebra finches.
AB  - The medial magnocellular nucleus of the anterior neostriatum (mMAN) is a small
      cortical nucleus which was previously identified as a component of the neural
      circuitry controlling vocal behavior in songbirds based on its efferent
      connection to the High Vocal Center (HVC), a major song control nucleus
      (Nottebohm et al. [1982] J. Comp. Neurol. 207:344-357; Bottjer et al. [1989] J.
      Comp. Neurol. 279:312-326). We have conducted tract tracing experiments (using
      wheat-germ agglutinin-horseradish peroxidase (WGA-HRP), the carbocyanine dye DiI,
      and biocytin) to determine the complete pattern of afferent and efferent
      connections of mMAN in adult male zebra finches. We confirmed the existence of an
      efferent projection from mMAN to HVC and discovered a novel projection to the
      region medial to caudal HVC called paraHVC (pHVC). Injections of retrograde
      tracers into mMAN showed that afferent input to mMAN originates from the
      dorsomedial nucleus of the posterior thalamus (DMP). Injections of DiI into DMP
      produced anterograde label over mMAN, thus confirming the DMP-to-mMAN projection.
      Interestingly, this anterograde label extended beyond the region of mMAN defined
      by HVC-projecting neurons into the immediately surrounding cortex. This extended
      terminal field of DMP efferents indicates that mMAN encompasses a core population
      of projection neurons surrounded by a shell of non-HVC-projecting neurons, both
      of which receive input from the dorsal thalamus. Analysis of retrograde DiI label
      resulting from DMP injections revealed two major sources of afferent input to DMP
      originating in regions of the archistriatum and hypothalamus. Inputs to DMP were
      distributed throughout the dorsal archistriatum and included the area that
      receives a projection from the parvicellular shell region of the lateral
      magnocellular nucleus of the anterior neostriatum, a song control nucleus, as
      well as the dorsal portion of the robust nucleus of the archistriatum, the motor
      cortical output of the song control system. The projections from song control
      regions of the archistriatum to DMP may feed information back into telencephalic
      song control circuitry via the DMP-->mMAN-->HVC/pHVC pathway. The other source of
      afferent input to DMP is located in the external cellular stratum of the lateral
      hypothalamus (SCE). This newly delineated SCE-->DMP-->mMAN-->HVC/pHVC pathway is
      the first report of a hypothalamic brain region neuroanatomically integrated with
      song control circuitry. Because hypothalamic brain regions are important for
      homeostasis and regulating behavior, the trans-synaptic circuitry of mMAN may
      help to integrate information about the bird's internal state, such as sexual
      maturation, with song learning and production.

PMID- 9183700
TI  - Calretinin immunoreactivity in the cerebral cortex of the lizard Psammodromus
      algirus: a light and electron microscopic study.
AB  - The present study describes the distribution and structural features of
      calretinin-immunoreactive neurons and fiber plexuses in the cerebral cortex of a
      lacertid lizard, at the light and electron microscopic levels, and also examines
      the colocalization of calretinin with parvalbumin and gamma-aminobutyric acid
      (GABA) in certain cortical regions. Calretinin-immunoreactive neurons are present
      throughout the cerebral cortex of Psammodromus and can be classified according to
      morphological and neurochemical criteria. Neurons in the medial cortex are small,
      spine-free and lack parvalbumin, whereas in the lateral cortex, calretinin
      immunoreactive neurons display sparsely spiny dendrites and also lack
      parvalbumin. The dorsomedial and dorsal cortices contain most of the calretinin
      cortical neurons, which were located almost exclusively in the deep plexiform
      layer. These neurons are large, with an extensive spine-free dendritic tree. Most
      of the calretinin-immunoreactive neurons of dorsomedial and dorsal cortices are
      GABAergic and contain parvalbumin. Calretinin-immunoreactive fibers form two main
      afferent systems in the cortical areas. One probably intrinsic inhibitory system,
      arising from the calretinin and parvalbumin GABAergic neurons in the dorsomedial
      and dorsal cortices, makes symmetrical synapses on the soma and proximal
      dendrites of neurons located in the cell layers of the same cortical areas. The
      other system is formed by extremely thin axons running within the superficial
      plexiform layers of the medial, dorsomedial and dorsal cortices. These axons make
      asymmetrical synapses on dendrites or dendritic spines. We suggest that this
      system, probably extrinsic excitatory, arises from neurons located in the basal
      forebrain.

PMID- 9183701
TI  - Neurokinin receptor mRNA localization in human midbrain dopamine neurons.
AB  - The structurally related neurokinin peptides, substance P and neurokinin A, are
      found in abundance within the substantia nigra of a variety of mammalian species.
      Although it has been established recently that the neurokinin-3 (NK3) receptor is
      the predominant neurokinin receptor found in rat substantia nigra and adjacent
      midbrain nuclei, the nature of the neurokinin receptor expressed in human
      midbrain has not been elucidated. In the present study, neurokinin receptor
      messenger RNA (mRNA) content within rat and human midbrain were directly compared
      by using quantitative in situ hybridization histochemistry. In contrast to the
      high abundance of NK3 receptor mRNA within dopamine (DA) cells of the rat
      midbrain, neurokinin-1 (NK1), but not NK3, receptor mRNA was localized to human
      midbrain DA cells. Within the human midbrain, the abundance of NK1 receptor mRNA
      differed significantly among the distinct DA cell-containing nuclei, with the
      highest level of expression seen in several subdivisions of the substantia nigra.
      Thus different neurokinin receptor subtypes apparently mediate the effects of
      substance P and neurokinin A on human versus rat DA neurons.

PMID- 9183702
TI  - Identification of catecholaminergic inputs to and outputs from aromatase
      containing brain areas of the Japanese quail by tract tracing combined with
      tyrosine hydroxylase immunocytochemistry.
AB  - In the quail brain, aromatase-immunoreactive (ARO-ir) neurons located in the
      medial preoptic nucleus (POM) and caudal paleostriatum ventrale/nucleus
      accumbens/nucleus striae terminalis complex (PVT/nAc/nST) receive
      catecholaminergic inputs identified by the presence of tyrosine hydroxylase
      immunoreactive (TH-ir) fibers and punctate structures. The origin of these inputs
      was analyzed by retrograde tracing with cholera toxin B subunit (CTB) or red
      latex fluospheres (RLF) combined with TH immunocytochemistry. CTB and RLF
      injected in the POM or PVT/nAc/nST were found in cells located in anatomically
      discrete areas in the telencephalon (hippocampus, septum, archistriatum),
      hypothalamus (many areas in periventricular position), thalamus, mesencephalon,
      and pons. In these last two regions, many retrogradely labeled cells were located
      in dopaminergic areas such as the retroruberal field (RRF), substantia nigra
      (SN), and area ventralis of Tsai (AVT) but also in noradrenergic cell groups such
      as the locus ceruleus and subceruleus. CTB tracing showed that most of these
      connections are bidirectional. Many retrogradely labeled cells contained TH-ir
      material. As a mean, 10-20% and 40-60% of the RLF-containing cells in the
      dopaminergic areas were TH-ir when RLF had been injected in the POM or
      PVT/nAc/nST, respectively. TH-ir cells projecting to the POM appeared to be
      mostly located in the periventricular hypothalamus and in AVT, whereas
      projections to the PVT/nAc/nST originated mainly in the SN (with significant
      contributions from the RRF and AVT). These data support the existence of
      functional relationships between aromatase and catecholamines.

PMID- 9183706
TI  - Trophic controls on stage transformations of a toxic ambush-predator
      dinoflagellate.
AB  - The toxic dinoflagellate, Pfiesteria piscicida, was recently implicated as the
      causative agent for about 50% of the major fish kills occurring over a three-year
      period in the Albemarle-Pamlico Estuarine System of the southeastern USA.
      Transformations between life-history stages of this dinoflagellate are controlled
      by the availability of fresh fish secretions or fish tissues, and secondarily
      influenced by the availability of alternate prey including bacteria, algae,
      microtauna, and mammalian tissues. Toxic zoospores of P. piscicida subdue fish by
      excreting lethal neurotoxins that narcotize the prey, disrupt its osmoregulatory
      system, and attack its nervous system. While prey are dying, the zoospores feed
      upon bits of fish tissue and complete the sexual phase of the dinoflagellate life
      cycle. Other stages in the complex life cycle of P. piscicida include cryptic
      forms of filose, rhizopodial, and lobose amoebae that can form within minutes
      from toxic zoospores, gametes, or planozygotes. These cryptic amoebae feed upon
      fish carcasses and other prey and, thus far, have proven less vulnerable to
      microbial predators than flagellated life-history stages. Lobose amoebae that
      develop from toxic zoospores and planozygotes during colder periods have also
      shown ambush behavior toward live fish. In the presence of abundant flagellated
      algal prey, amoeboid stages produce nontoxic zoospores that can become toxic and
      form gametes when they detect what is presumed to be a threshold level of a
      stimulatory substance(s) derived from live fish. The diverse amoeboid stages of
      this fish "ambush-predator" and at least one other Pfiesteria-like species are
      ubiquitous and abundant in brackish waters along the western Atlantic and Gulf
      Coasts, indicating a need to re-evaluate the role of dinoflagellates in the
      microbial food webs of turbid nutrient-enriched estuaries.

PMID- 9183707
TI  - Effect of osmotic stress on the rate of release of acid phosphatase by Leishmania
      donovani promastigotes.

PMID- 9183708
TI  - Small subunit ribosomal RNA sequences unite alternate actinosporean and
      myxosporean stages of Myxobolus cerebralis the causative agent of whirling
      disease in salmonid fish.
AB  - The alternating myxosporean and actinosporean stages of the myxozoan parasite
      Myxobolus cerebralis (Hofer 1903) from its salmonid fish and aquatic oligochaete
      hosts, respectively, were compared for sequence homology of the small subunit
      (18S) ribosomal RNA genes. A 99.8% similarity between the sequences of these two
      stages was substantially greater than that of M. cerebralis compared to two other
      Myxobolus sp. from salmonid fish. Our results are the first molecular evidence
      confirming the alternating stages, initially described by Wolf and Markiw [25]
      for the life cycle of M. cerebralis but found in two different taxonomic classes
      (Myxosporea and Actinosporea) are indeed forms of the same organism. Sequencing
      of rRNA genes of the actinosporean stage followed by development of specific
      primers for DNA amplification of the myxosporean stage, as in our study, should
      be applied to solve other myxozoan life cycles. Additionally, these approaches
      will in the future provide useful diagnostic reagents for the detection and study
      of this important group of fish pathogens.

PMID- 9183710
TI  - Phylogenetic position of Amblyospora Hazard & Oldacre (Microspora:Amblyosporidae)
      based on small subunit rRNA data and its implication for the evolution of the
      microsporidia.
AB  - Sequences of the small subunit rRNA genes of Amblvospora california and an
      Amblyospora sp. from Culex salinarius were determined. These sequences were
      compared phylogenetically with 16 other microsporidia. The results suggest
      Amblyospora forms a sister taxon to the rest of the microsporidia examined. The
      basal position of Amblyospora is discussed with respect to the evolution of
      microsporidian life cycles. These sequences represent the longest microsporidian
      small subunit rRNA genes sequenced to date, 1,359 and 1,358 bp. respectively.
      Structural features and GC content (49% for both) are comparable to those of
      other microsporidia which have been sequenced.

PMID- 9183713
TI  - Activities of enzymes of carbohydrate and energy metabolism of the spores of the
      microsporidian, Nosema grylli.
AB  - The presence of 14 enzymes was investigated using purified spores of the
      microsporidian Nosema grylli from fat body of the crickets Gryllus bimaculatus.
      Glucose 6-phosphate dehydrogenase (EC 1.1.1.49), phosphoglucomutase (EC 5.4.2.2),
      phosphoglucose isomerase (EC 5.3.1.9), fructose 6-phosphate kinase (EC 2.7.1.11),
      aldolase (EC 4.1.2.13), 3-phosophoglycerate kinase (EC 2.7.2.3), pyruvate kinase
      (EC 2.7.1.40) and glycerol 3-phosphate dehydrogenase (EC 1.1.1.8) were detected
      with activities of 15 +/- 1, 7 +/- 1, 1,549 +/- 255, 10 +/- 1, 5 +/- 1, 16 +/- 4,
      6 +/- 1 and 16 +/- 2 nmol/min mg protein, respectively. Hexokinase (EC 2.7.1.1),
      NAD-dependent malate dehydrogenase (EC 1.1.1.37), malic enzyme (EC 1.1.1.40),
      lactate dehydrogenase (EC 1.1.1.27), alcohol dehydrogenase (EC 1.1.1.1) and
      succinate dehydrogenase (EC 1.3.99.1) were not detectable. These results suggest
      the catabolism of carbohydrates in microsporidia occurs via the Embden-Meyerhof
      pathway. Glycerol 3-phosphate dehydrogenase may reoxidize NADH which is produced
      by glyceraldehyde 3-phosphate dehydrogenase in glycolysis.

PMID- 9183709
TI  - Cellulase activity of Leishmania major in the sandfly vector and in culture.
AB  - The secretion of cellulose-degrading enzymes by Leishmania promastigotes in
      culture and in the sandfly vector was demonstrated. Two types of activity of
      cellulase enzyme-complexes were measured: endoglucanases, which randomly cleave
      cellulose chains and cellobioydrolases, which remove cellobiose from the
      nonreducing end of the molecule. The assays demonstrated that enzymes with these
      activities were secreted into the culture medium by Leishmania major, L.
      donovani, and L. braziliensis. These activities were also found in cultures of
      Sauroleishmania agamae, Leptomonas seymouri, Herpetomonas muscarum, Crithidia
      fasciculata and Trypanosoma brucei brucei that had a relatively low endoglucanase
      activity. Both endoglucanase and cellobiohydrolase activities were found in the
      gut of L. major-infected Phlebotomus papatasi, while gut preparations of
      uninfected sandflies had only cellobiohydrolase activity. The similar growth of
      L. major parasites in medium supplemented with either cellulose or glucose
      suggests these parasites can utilize cellulose.

PMID- 9183714
TI  - Cloning and molecular analysis of the plasma membrane Ca(2+)-ATPase gene in
      Paramecium tetraurelia.
AB  - We have determined the DNA sequence of the gene encoding the protein of the
      plasma membrane Ca(2+)-ATPase in Paramecium tetraurelia. The predicted amino acid
      sequence of the plasma membrane Ca(2+)-ATPase shows homology to conserved regions
      of known plasma membrane Ca(2+)-ATPases and contains the known binding sites for
      ATP (FITC), acylphosphate formation, and calmodulin, as well as the "hinge"
      region: all characteristics common to plasma membrane Ca(2+)-ATPases. The deduced
      molecular weight for this sequence is 131 kDa. The elucidation of this gene will
      assist in the studies of the mechanisms by which this excitable cell removes
      calcium entering through voltage gated calcium channels and the pump functions in
      chemosensory signal transduction.

PMID- 9183715
TI  - Opportunistic properties of Nosema algerae (Microspora), a mosquito parasite, in
      immunocompromised mice.
AB  - In the last ten years microsporidia have been recognized as opportunistic
      pathogens in AIDS patients. The sources of infection and the mechanisms of
      transmission of these organisms in humans are mostly uncertain. Transmission of
      invertebrate microsporidia to mammals is normally considered impossible,
      temperature being a limiting factor for development. Mice treated with cortisone
      acetate and with cyclosporin A, respectively, as well as athymic nice were
      injected intravenously, intranasally, perorally and subcutaneously with spores of
      Nosema algerae, a microsporidian species of culicine mosquitoes. No infection
      could be detected in tissue samples of cortisone acetate and cyclosporin A
      treated mice. However, the experimental inoculation of spores into the tail and
      foot of athymic mice caused severe infection in skeletal muscles and the
      connective tissue. In some tails, nerve tissue and bone marrow were also
      infected. Vegetative stages and spores were seen in direct contact to host cell
      cytoplasma. For the first time the prolonged and progressive development of an
      invertebrate microsporidium in a mammalian host is shown. The possibility of
      invertebrate microsporidia as a source of human microsporidiosis should now be
      taken into consideration.

PMID- 9183718
TI  - Determination of left ventricular mass in clinical practice.
AB  - Left ventricular (LV) mass is affected by cardiovascular diseases and disorders.
      An increase in LV mass during a disease process may suggest disease progression,
      while a decrease in mass may suggest disease regression. Thus, LV mass can be
      used to follow the natural history of a disease or disorder and to evaluate the
      effect of therapeutic interventions. Although several methods have been used to
      determine LV mass in clinical practice, their application requires knowledge of
      their limitations and advantages. Most such techniques are insufficiently
      sensitive or specific to define LV mass changes in individual patients.
      Consequently, it may be more beneficial to evaluate therapy-related changes in LV
      mass in large patient groups.

PMID- 9183719
TI  - Echocardiography in mitral valve repair for mitral regurgitation: the surgeon's
      needs.
AB  - Mitral valve repair has become the operation of choice for mitral regurgitation.
      It is often technically more demanding than valve replacement. The role of
      echocardiography has now extended beyond the identification of severe mitral
      regurgitation that would benefit from surgical correction. It helps the surgeon
      to assess valve reparability preoperatively, to assess the need for valve surgery
      in equivocal cases of ischemic mitral regurgitation, to plan the operation, and
      to assess valve function after repair. This article aims to discuss the role of
      echocardiography in providing the information needed by the surgeon for
      successful mitral valve repair. The echocardiographer must understand the
      surgeon's needs, while surgeons should understand both the benefits and
      limitations of echocardiography.

PMID- 9183720
TI  - Early diagnosis of obstructed aortic valve prostheses: a clinical challenge.

PMID- 9183721
TI  - Doppler echocardiographic study of three different mechanical valves in the
      aortic position: the use of external nominal diameter indexed to body surface
      area.
AB  - BACKGROUND AND AIMS OF THE STUDY: Previous studies have demonstrated the benefit
      of indexing body surface area (BSA) with ventriculo-arterial orifice diameters
      (or calculated effective surface dynamics) and with nominal external diameters of
      valves in order to study hemodynamic profiles in vivo or determine the clinical
      influence of this parameter. This study analyzes the relationship between BSA and
      nominal external diameter of mechanical valves implanted in the aortic position.
      It also evaluates the potential interest of using these diameters indexed to BSA
      in an echo-Doppler study of valves. METHODS: During 1994, a prospective echo
      Doppler study of three models of mechanical valves in the aortic position was
      carried out. RESULTS: The echo-Doppler parameters of the aortic St. Jude Medical,
      Sorin Bicarbon and Dideco Monostrut prostheses have been studied with regard to
      nominal external diameters and were found identical to published data. There were
      no significant differences in these parameters between the three valves. In 128
      patients, prosthetic external diameters were evenly distributed heterogeneously
      with regard to BSA. Indexing of nominal external diameter with BSA appeared a
      more reliable reference to study different echo-Doppler parameters, minimizing
      the effect of cardiac output. CONCLUSION: The in vivo echo-Doppler determination
      at rest of valve hemodynamic profiles should be carried out with reference to the
      nominal external diameter indexed to the BSA.

PMID- 9183722
TI  - The role of transesophageal echocardiography in patients with chronic renal
      failure at low and high risk of endocarditis.
AB  - BACKGROUND AND AIMS OF THE STUDY: The benefits of transesophageal
      echocardiography (TEE) may depend on the clinical likelihood of infective
      endocarditis, but little data exist on patients at low risk. METHODS AND RESULTS:
      We studied 32 patients with renal failure with either a low (n = 21) or high (n =
      11) level of clinical suspicion for infective endocarditis. In the low-risk
      cases, TEE provided no new information whether the transthoracic echo was normal
      or abnormal, although it did confirm that an echogenic mass was more likely to be
      a calcific deposit than a vegetation. In the high-risk cases, transthoracic
      echocardiography was always abnormal but TEE added new information in seven out
      of 11 cases-positively in six, and by exclusion in one. TEE detected signs of
      complications of infective endocarditis in one case. CONCLUSIONS: We conclude
      that, when the clinical suspicion of endocarditis is low, TEE is rarely
      necessary.

PMID- 9183723
TI  - Use of dobutamine stress echocardiography in assessing mechanical aortic
      prostheses: comparison with exercise echocardiography.
AB  - BACKGROUND AND AIMS OF THE STUDY: Relatively high resting flow velocities are
      occasionally seen in asymptomatic patients with apparently normal mechanical
      aortic prostheses. Doppler echocardiography in conjunction with bicycle exercise
      or dobutamine have been used to 'unmask' symptoms or abnormal hemodynamics in
      these patients. The aim of this study was to compare the Doppler-derived
      hemodynamic response to exercise and to dobutamine in patients with normally
      functioning mechanical aortic prostheses. METHODS: Bicycle ergometry (from 200
      400 kg x m/min) and dobutamine (from 5-40 micrograms/kg/min) in conjunction with
      Doppler echocardiography were performed in 25 asymptomatic patients (21 men, four
      women; mean age 61 years) with mechanical aortic prostheses (range: 19 mm to 27
      mm) who had normal resting hemodynamics and normal left ventricular function.
      Aortic valve area (continuity equation) and maximal instantaneous and mean
      gradients were estimated at rest and at peak stress. RESULTS: Target heart rate
      was achieved in 10/25 (40%) patients with exercise, and in 21/25 (84%) with
      dobutamine (p < 0.005). At peak stress, exercise induced a 25% increase in peak
      flow velocity, a 55% increase in valve gradients, and no significant change in
      valve area. In comparison, dobutamine induced a 48% increase in peak flow
      velocity, a 105% increase in valve gradients, and also no significant change in
      valve area. The flow velocity and pressure gradients at peak stress were
      significantly higher with dobutamine than with exercise. CONCLUSIONS: In normally
      functioning aortic valve prostheses, the target heart rate can be reached more
      often with dobutamine than with supine bicycle exercise. Despite significant
      increase in the transvalvular gradients, the valve area remained unchanged. The
      clinical significance of exercise or dobutamine in symptomatic patients with
      mechanical prostheses is yet to be proven.

PMID- 9183724
TI  - Cineradiographic evaluation of ATS open pivot bileaflet valves.
AB  - BACKGROUND AND AIMS OF THE STUDY: Echocardiography and cineradiography are both
      valuable for the evaluation of prosthetic valve function, especially of
      mechanical valves. Although Doppler echocardiography data are available for the
      recently developed ATS valve, cineradiographic evaluation of leaflet movement of
      the valve has not been performed. MATERIALS AND METHODS: Five patients received
      aortic and another five mitral valve replacement with the open pivot ATS
      bileaflet prosthetic valve. There were three men and seven women; mean patient
      age was 58.8 years. Cineradiographic and Doppler echocardiographic evaluations of
      the ATS valve were performed early after surgery in all 10 patients. RESULTS:
      There were no early deaths after surgery or after discharge from the hospital. No
      valve-related complications were seen, and no clinical symptoms or signs of
      prosthetic malfunction were observed during the follow up period. Doppler-derived
      values of the ATS valve were comparable with those previously reported; however,
      cineradiography of the valve demonstrated that the mean angle enclosed by the two
      open leaflets was 37.6 degrees (range: 34 degrees to 44 degrees) in the aortic
      position and 29.7 degrees (range: 20 degrees to 35 degrees) in the mitral
      position. Mean leaflet mobility was 93.0 degrees (range: 86 degrees to 96
      degrees) in the aortic position and 100.0 degrees (range: 92 degrees to 110
      degrees) in the mitral position. Thus, the opening of the normally functioning
      ATS valves in vivo was less than that observed in vitro and reported by the
      manufacturer. CONCLUSIONS: These results suggest that unevenly distributed blood
      flows with different velocities through the two side orifices and the central
      orifice may result in incomplete opening of the ATS leaflets, which respond with
      great sensitivity to localized blood flow. Our findings appear to be important to
      avoid the removal of a normally functioning ATS valve only because the leaflet
      opening appears to be 'restricted'.

PMID- 9183725
TI  - Shop order fracture rate as a risk factor for strut fracture in Bjork-Shiley CC60
      degrees heart valves.
AB  - BACKGROUND AND AIMS OF THE STUDY: Previous studies have implicated a number of
      characteristics that predict strut fracture in Bjork-Shiley convexo-concave heart
      valves, including valve size and position, opening angle, and weld date. This
      study examines whether the specific batch (shop order) with which a valve is
      associated during manufacture is related to the risk of fracture. MATERIAL AND
      METHODS: Our case-control study of CC60 degrees valves obtained detailed
      information on the manufacturing characteristics of 147 case and 1094 control
      valves used. Shop order fracture rate for each valve (percentage of other valves
      in the same shop order with a fracture) was obtained from the research database
      maintained by the valve manufacturer. RESULTS: Shop order was associated with
      fracture risk. Valves originating from shop orders with the highest two
      categories of fracture rate were at approximately twice the risk of fracture as
      other valves, after accounting for the effect of known risk factors. CONCLUSIONS:
      Shop order information may provide additional data for assessing the likelihood
      of valve fracture in individuals being considered for prophylactic explant of
      heart valves.

PMID- 9183726
TI  - Postoperative hemodynamics of two bileaflet heart valves in the aortic position.
AB  - BACKGROUND AND AIMS OF THE STUDY: In vivo hemodynamic assessment of bileaflet
      aortic valve prostheses using standardized echocardiography is still uncommon;
      hence, adequate comparison of valve types can rarely be made. We compared the
      postoperative hemodynamics of St. Jude Standard valves (SJS) with those of Sorin
      Bicarbon valves (BC) implanted in the aortic position, using pulsed, continuous
      and color Doppler echocardiography. METHODS: The examination was performed four
      months after aortic valve prosthesis implantation in 76 patients (39 SJS valves,
      37 BC valves). Valve sizes varied from 19 mm to 25 mm. Maximal and mean
      instantaneous pressure gradients were measured by Doppler echocardiography.
      Effective valve orifice area (EOA) was calculated and prosthetic valve
      regurgitation was assessed by color Doppler flow imaging. RESULTS: At valve sizes
      of 21 mm, 23 mm and 25 mm, SJS valves had a significantly lower EOAs than BC
      valves (p < 0.05). However, for a given nominal size, BC valves are larger, i.e.
      they have a larger anatomic (AOA) and geometric orifice area (GOA) than SJS
      valves. Consequently, BC valves were implanted in patients with a larger left
      ventricular outflow tract (p < 0.05). When EOA is related to the corresponding
      AOA, BC valves still show a larger EOA than SJS valves (p < 0.05). Prosthetic
      valve regurgitation is low in both valve types. CONCLUSIONS: (a) Nominal valve
      size is not always a good basis for comparison of hemodynamic profiles between
      valve types. (b) Using the relationship between EOA and AOA, the hemodynamic
      profile of BC valves in the aortic position is shown to be superior to that of
      SJS valves.

PMID- 9183727
TI  - Mitral valve replacement with total preservation of native valve and subvalvular
      apparatus.
AB  - BACKGROUND AND AIMS OF THE STUDY: Preservation of the mitral valve and
      subvalvular apparatus was introduced clinically in the early 1960s, but for two
      decades the technique for mitral valve replacement included excision of both
      leaflets and their attached chordae tendineae. Lately, emphasis has been replaced
      on retaining the mitral subvalvular apparatus during valve replacement because of
      its role in left ventricular function. Hence, during the past six years, when
      performing mitral valve replacement we have, when possible, preserved the
      valvular and sub-valvular mitral apparatus. METHODS: Between January 1990 and
      November 1996, complete retention of all mitral tissue in connection with mitral
      valve replacement was performed in 58 patients (23 women and 35 men). Mean age
      was 63 years (range: 23 years to 77 years). Coronary bypass was a concomitant
      procedure in 19 patients; both the mitral and aortic valve was replaced in four
      cases. Calcified and/or stenotic valves were not a contraindication for the
      procedure; calcified plaques were removed. Adhesion between anterior and
      posterior leaflets was treated with sharp dissection. Valve and subvalvular
      tissue were preserved. The leaflets were reefed within the valve-sutures and
      compressed between the sewing ring and the native annulus when implanting the
      valve prosthesis. Chordal tension on the ventricle is thus maintained and the
      chordae pulled away from the valve effluent. RESULTS: Six patients died in the
      postoperative period and three had transient neurological symptoms. In no patient
      was death or transient neurological symptoms a consequence of the retention of
      mitral leaflets with subvalvular apparatus. CONCLUSIONS: We find the described
      technique to be useful not only in valve insufficiency but also in valve stenosis
      when preserving the mitral leaflets with sub-valvular apparatus during valve
      replacement. The technique is without procedure-related complications and
      prevents obstruction of left ventricular outflow tract.

PMID- 9183728
TI  - Periprosthetic leaks and valve dehiscence: alternative methods of repair.
AB  - BACKGROUND AND AIMS OF THE STUDY: Reoperations for periprosthetic leaks (PL) and
      valve dehiscence (VD) are associated with high mortality and substantial
      recurrence rate. Standard methods of repair are often not feasible due to
      friability of the annulus tissue or lack of space to locate the sutures. We have
      therefore used a variety of unconventional methods to close the leaks securely.
      CLINICAL MATERIAL AND METHODS: The clinical records of 25 patients reoperated for
      PL and VD between 1989 and 1995 were reviewed. Eighteen patients had aortic and
      seven mitral PL. Patients with mechanical heart valves were more frequently
      reoperated than those with bioprostheses (2.1% versus 0.7%). The PL was repaired
      in 16 cases, and the prosthesis was exchanged in nine cases with VD or large
      leaks. Six of the latter nine patients had active prosthetic endocarditis. A
      variety of surgical techniques was used to repair the leaks, including placing
      sutures from outside the aortic wall, through the atrial and ventricular septum,
      through the free left atrial wall and closure by single or double patch
      technique. RESULTS: Hospital mortality was 4% (1/25 patients) and one-year
      mortality 12.5%. None of the patients except one with active prosthetic
      endocarditis needed a second reoperation. CONCLUSIONS: If PLs are difficult to
      close with standard surgical technique, the alternative methods described might
      be useful. These methods can also be used during primary valve replacements where
      leaks remain.

PMID- 9183729
TI  - The hybrid autograft/xenograft aortic valve.

PMID- 9183730
TI  - Repopulation of freeze-dried porcine valves with human fibroblasts and
      endothelial cells.
AB  - BACKGROUND AND AIMS OF THE STUDY: There is a need for a replacement cardiac valve
      constructed from non-immunogenic materials but incorporating living, and
      preferably autologous, cells. The object of this study was to colonize freeze
      dried porcine valve leaflets with human fibroblasts and vascular endothelial
      cells. METHODS: Porcine pulmonary valve leaflets were freeze-dried to produce a
      porous matrix having communicating cavities of appropriate dimensions for
      fibroblast repopulation. Cultured human fibroblasts and vascular endothelial
      cells that had been cryopreserved by standard methods were added to freeze-dried
      leaflets. Following culture at 37 degrees C, the leaflets were examined by
      confocal scanning microscopy and transmission electron microscopy. RESULTS:
      Mechanical perforation of the leaflet surface permitted colonization of the
      freeze-dried matrix by fibroblasts; under the conditions we studied, the cell
      density did not reach physiologic levels but those cells that were present were
      well attached and metabolically active. Gentle cotton abrasion of the surface of
      the freeze-dried leaflets provided a suitable substrate for endothelial cell
      attachment and confluence was achieved in 10 days. Leaflets were perforated,
      cultured with human fibroblasts for 10 days, then gently rubbed with a cotton bud
      and cultured for a further 10 days with human endothelial cells. The endothelial
      cells formed a confluent layer on the surface and viable fibroblasts were present
      within the substance of the leaflet. CONCLUSION: Although these results are
      preliminary, they demonstrate the basic feasibility of this approach to the
      production of xenogeneic valves that contain the patient's own cells.

PMID- 9183732
TI  - In vivo and in vitro models of calcification in porcine aortic valve cusps.
AB  - Both in vivo and in vitro models have been developed to study the initiation and
      progression of dystrophic calcification of bioprosthetic heart valves.
      Circulatory in vivo models have proven to be the most predictive of the success
      of a new valve designs or anticalcification schemes; however, these experiments
      are time consuming and expensive. An appealing alternative to circulatory
      implantation is the sub-cutaneous rat implantation model. This model is
      inexpensive and calcification occurs rapidly. Recent studies have shown, however,
      that some anticalcification methods work well in the subcutaneous model but are
      ineffective in the circulatory model. In vitro models would provide the most
      convenient method for testing new anticalcification strategies but, to date, no
      in vitro test system has been developed which produces calcification of rates and
      with morphology comparable with that in vivo models. We have also studied the
      effects of collagen damage and cell extraction on the calcification of porcine
      aortic valve cusps both in vitro and in the subcutaneous rat model, and found
      significant differences in the patterns of mineralization. The objectives of this
      paper therefore are to compare and contrast the different experimental protocols
      and procedures reported in the literature to better define the effects of
      different model systems on the calcification process.

PMID- 9183731
TI  - Biocompatibility and immunologic properties of pericardial tissue stabilized by
      dye-mediated photooxidation.
AB  - BACKGROUND AND AIMS OF THE STUDY: Bovine and porcine pericardial tissues
      stabilized by dye-mediated photooxidation have found application as bioprosthetic
      heart valve material. METHODS: To help predict clinical performance, a series of
      tests were performed to assess the biocompatibility and immunologic properties of
      these materials. RESULTS AND CONCLUSIONS: Photooxidized bovine or porcine
      pericardium sterilized with an iodine-based solution were found to be non
      cytotoxic, non-hemolytic, and non-mutagenic. Oil or saline extracts of these
      tissues passed tests for intracutaneous toxicity (irritation), acute systemic
      toxicity, and subchronic toxicity. Histopathology of 90-day implants of these
      tissues in the rabbit model demonstrated no significant macroscopic reaction and
      only slight microscopic response. Using a rabbit model to assess immune response,
      both bovine and porcine pericardial tissues elicited low levels of antibody.
      Furthermore, tissue photooxidation or iodine sterilization did not increase the
      overall level of antibodies. Glutaraldehyde-treated tissue also elicited low
      antibody levels which were higher than photooxidized tissue-induced levels.
      Absorption studies indicated that the photooxidation process may generate new
      epitopes, possibly collagen cross-links. Using the juvenile sheep model to assess
      in vivo performance, bioprosthetic valves made with photooxidized tissue were
      implanted and allowed to serve as functional implants for up to two years. Upon
      explant, the photooxidized pericardial leaflets were found to be non-calcific and
      partially covered with a layer of host cells. Histological cross-sections stained
      with von Willebrand's factor confirmed this layer as endothelial cells.

PMID- 9183733
TI  - Reoperation for prosthetic thrombosis and acute neurologic injury.
AB  - Open-heart surgery in patients with recent cardiogenic embolic stroke represents
      a difficult management problem. We present a patient who developed thrombosis of
      a mitral tilting-disc prosthesis complicated by repeat cerebral embolic episodes
      that resulted in acute neurologic injury. We believe that in such patients the
      indication for reoperation must be individually evaluated but it is justified in
      young subjects, even in the presence of severe neurologic damage.

PMID- 9183734
TI  - In response to "Formaldehyde Replaces Glutaraldehyde in Porcine Bioprosthetic
      Heart Valves".

PMID- 9183735
TI  - Stentless fresh pulmonary homograft for recurrent mitral prosthetic valve
      endocarditis.

PMID- 9183736
TI  - Accumulation and proliferation of adult leg muscle precursors in Manduca are
      dependent on innervation.
AB  - During metamorphosis, the larval thoracic legs of the moth Manduca sexta are
      replaced by new adult legs. The leg motoneurons do not die after the loss of the
      larval muscles, but persist to innervate the new adult leg muscles (Kent and
      Levine, 1988). The adult muscles form from myoblasts that originate in specific
      production sites within the legs and migrate to the sites of muscle formation,
      where they accumulate, proliferate, and fuse to form myofibers (Consoulas et al.,
      1996b). Throughout adult leg muscle development, there is a close association
      between nerves and the developing muscles, suggesting a role for the nervous
      system in myogenesis (Consoulas et al., 1996a). This prediction was confirmed and
      the role of the nervous system clarified in the present study by cutting the
      larval leg nerves prior to metamorphosis. Although myoblasts were generated and
      migrated normally in the operated leg, they failed to accumulate in the
      appropriate regions. The myoblasts did not die, but failed to proliferate and
      remained in the denervated legs as dispersed cells or as aggregates in
      inappropriate regions. In about 26% of cases, this resulted in the formation of
      adult legs that lacked muscles. In the remaining cases, however, delayed
      regeneration of the leg nerve occurred and small muscles appeared in the more
      proximal segments of the denervated legs. Each muscle fiber in these operated
      legs bore motor terminals belonging to axons of the leg nerves which had grown
      out from the proximal nerve stump and invaded the leg. Following the delayed
      appearance of motor axons, myoblasts aggregated and underwent proliferation and
      differentiation into muscle fibers. In a second set of experiments, denervation
      was performed later, after myoblasts had aggregated to establish anlagen.
      Myoblast proliferation was reduced but differentiation continued. These
      observations suggest that motor nerves are essential for both the accumulation of
      myoblasts into the correct areas of muscle development and the appropriate level
      of proliferation.

PMID- 9183737
TI  - Neuronal precursors of the adult rat subependymal zone persist into senescence,
      with no decline in spatial extent or response to BDNF.
AB  - The adult mammalian brain continues to harbor ependymal/subependymal zone (SZ)
      precursor cells, which can give rise to neurons in vitro. In adult rats, explants
      of the rostral 6-7 mm of the SZ give rise to neurons in vitro, and over this
      entire expanse, neuronal survival is supported specifically by brain-derived
      neurotrophic factor (BDNF). We asked whether either the (a) spatial distribution,
      (b) abundance, or (c) BDNF responsiveness of the neuronal precursor population
      was affected by age. Explants of three rostrocaudally defined regions were taken
      from both young and old rats (3 and 20 months old, respectively), and cultured in
      2% fetal bovine serum-containing media with or without added BDNF (20 ng/ml). The
      extent of neuronal production by these explants varied only minimally with their
      level of derivation, such that substantial outgrowth was observed at each level
      tested. Neuronal outgrowth was marginally higher and more rapid in achieving its
      maximal extent in the 3-month-old rats compared with their aged counterparts, but
      neuronal outgrowth was robust at each age tested. The duration of survival of SZ
      derived neurons did not differ between the young and old rats. At both ages, BDNF
      supported the survival of these new adult neurons. The extent of BDNF's influence
      was independent of both the age of the donor rat and the rostrocaudal level at
      which the parent SZ explant was taken. Thus, the neuronal precursors of the rat
      brain persist into senescence; the size of the precursor pool attenuates
      minimally with age, and its spatial extent remains constant. The neurons
      generated from these precursors can respond to BDNF throughout life.

PMID- 9183738
TI  - Myosin functions in Xenopus retinal ganglion cell growth cone motility in vivo.
AB  - The role of myosins in Xenopus retinal ganglion cell growth cone motility in the
      optic tract was studied using two pharmacologic inhibitors with different
      specificities. 2,3-Butanedione monoxime (BDM) disrupts myosin-actin interactions
      of all myosins, and ML-7 specifically inhibits activation of myosin II. Both
      inhibitors caused growth cones to assume a collapsed morphology and decreased
      growth cone speed. Similar effects were observed in vitro. Interestingly, the
      effects of the two inhibitors, while similar, were clearly distinguishable,
      raising the possibility that different myosins may have different functional
      roles in growth cone motility. BDM caused growth cones to withdraw lamellipodia
      and some filopodia and eventually to freeze, whereas ML-7 caused total collapse
      and retraction. Concentrations of BDM and ML-7 that had no effect when applied
      independently stopped growth cones when applied simultaneously, suggesting that
      these inhibitors act synergistically on myosin function, thus providing evidence
      of specificity. These results imply that normal growth cone motility in the
      molecularly and spatially complex environment of the living brain requires myosin
      function.

PMID- 9183739
TI  - Embryonic rat spinal cord neurons change expression of glycine receptor subtypes
      during development in vitro.
AB  - The expression of functional glycine receptors (GlyRs) by embryonic rat spinal
      cord neurons during development in vitro was investigated using whole-cell patch
      clamp recordings. Functional GlyRs were expressed by most neurons within 1 day in
      vitro, and by all neurons from 4 days onward. However, the extent to which
      responses to glycine were blocked by the antagonist strychnine differed
      significantly between the first few days and 8 days in culture. Responses to
      glycine by neurons during the first few days in culture exhibited significantly
      less blockade by strychnine than those in neurons after 1 week in culture.
      Responses to glycine at both ages reflected an increased conductance to chloride
      ions, ruling out involvement of N-methyl-D-aspartate type glutamate receptors,
      and were not due to cross activation of gamma-aminobutyric acid receptors.
      Monoclonal antibody 4a, which recognizes multiple subtypes of rat GlyR alpha
      subunits, labeled most neurons as early as 1 day in vitro, confirming that
      neurons express some form of GlyR alpha subunits by the first day in culture.
      These results show that rat spinal cord neurons express GlyRs early in their
      differentiation in vitro, and they suggest that individual neurons express as
      functional, cell-surface GlyRs a strychnine-insensitive isoform of the GlyR,
      possibly the previously described alpha 2* subunit. In addition, these results
      indicate that the expression of GlyR isoforms changes from predominantly a
      strychnine-insensitive isoform to other, strychnine-sensitive isoform(s) GlyR
      during development in vitro.

PMID- 9183740
TI  - Aberrant expression of c-Fos accompanies photoreceptor cell death in the rd
      mouse.
AB  - Selective degeneration of rod photoreceptor cells in the retinal degenerative
      (rd) mouse prior to their complete maturation is thought to result from elevated
      cyclic guanosine monophosphate (cGMP) levels owing to the inherited defect in
      cGMP-phosphodiesterase. To investigate potential signaling pathways which might
      lead to apoptotic death of photoreceptors in the rd retina, the expression of
      immediate-early genes (IEG) of the activating protein-1 transcription factor (AP
      1) family was examined. Increasing numbers of apoptotic photoreceptor nuclei were
      observed in the outer nuclear layer of the rd mouse beginning at postnatal day
      (P) 10. The peak incidence of apoptotic cells was observed at P13; by P16, almost
      the entire population of photoreceptors had been lost. Although c-Fos-like
      immunoreactivity was absent in photoreceptors of normal retinas, we observed that
      commencing at around P10, increasing numbers of rod photoreceptors in the rd
      retina exhibited nuclear staining for c-Fos protein. While no change in the
      distribution patterns of other members of the AP-1 family (c-Jun, JunB, and JunD)
      was observed in photoreceptors, Muller cell nuclei were transiently
      immunoreactive for c-Jun on P11. The incidence of c-Fos-positive photoreceptors
      peaked sharply at P12, 1 day earlier than the peak in apoptosis. Furthermore, the
      population of c-Fos-positive photoreceptors was distinct from apoptotic
      photoreceptors exhibiting chromatin condensation. The aberrant expression of c
      Fos protein in rod photoreceptors immediately prior to their death in the rd
      mouse raises the possibility that c-Fos may be directly or indirectly involved in
      triggering the apoptotic cascade. Furthermore, the additional finding of c-Jun
      induction in Muller glia suggests that the IEG response to photoreceptor
      degeneration involves both intra- and intercellular signal transduction pathways.

PMID- 9183741
TI  - Structural organization of developing acetylcholine receptor aggregates.
AB  - We report the first quantitative ultrastructural analysis of newly formed
      acetylcholine receptor aggregates. Aggregates were induced in Xenopus muscle cell
      cultures with agrin, labeled with gold particles, and detected using high
      resolution scanning electron microscopy. Aggregates are readily discernible at
      the ultrastructural level within 2 h of stimulation by agrin. The size and
      density profiles of the developing aggregates show that receptors reach maximal
      density very quickly in small "nano-aggregates" and that the aggregation process
      is not limited by the diffusion rate of the receptor. Quantitative analysis of
      label locations indicates that the receptor distribution within aggregates is
      nonrandom. Instead, the newly aggregated receptors appear to be bound to a
      localized scaffold conforming to a hexagonal (close-packed) geometry with a
      spacing of approximately 9.9 nm.

PMID- 9183742
TI  - Dynamics of process formation during differentiation of tectal neurons in
      embryonic zebrafish.
AB  - Neurons acquire their distinct shapes after passing through many transitional
      stages in early development. To reveal the dynamics and spatiotemporal sequence
      of process formation in situ, the growth of neurons in the optic tectum of live
      zebrafish embryos (54 to > 100 h old) was monitored using time-lapse
      videorecordings. Neurons were labeled by injecting the fluorescent vital dye DiO
      into the cell-rich layer of the developing tectum in 50- to 70-h-old embryos. In
      phase 1, tectal neurons possess an apical "primary process" which reaches to the
      ventral aspect of the tectal neuropil. The primary process produces at its tip
      short transitory branches, some with growth cones, over a period of roughly 6 h.
      One of the growth cones then elongates rapidly and grows toward the caudal tectum
      via a route characteristic of efferent axons. After retraction of excess branches
      and growth cones, branching activity resumes at the tip of the primary process to
      form the dendritic tree (phase 2). The dendritic tree develops in the tectal
      neuropil through emission and retraction of many branches during a period of > 20
      h (our longest continuous time-lapse movie). The tectal territory "explored" in
      this way is larger than the area finally covered by the tree resulting from
      growth and loss of branches. The dynamics observed here directly are probably
      characteristic for dendrite formation in vertebrates. Moreover, consistent with
      the sequence of neuronal differentiation observed in vitro, the growth of the
      axon precedes that of the dendrites, although both emerge from a common primary
      process in this type of tectal neuron.

PMID- 9183743
TI  - The central pathway of primary olfactory axons is abnormal in mice lacking the N
      CAM-180 isoform.
AB  - Although N-CAM has previously been implicated in the growth and fasciculation of
      axons, the development of axon tracts in transgenic mice with a targeted deletion
      of the 180-kD isoform of the neural cell adhesion molecule (N-CAM-180) appears
      grossly normal in comparison to wild-type mice. We examined the organization of
      the olfactory nerve projection from the olfactory neuroepithelium to glomeruli in
      the olfactory bulb of postnatal N-CAM-180 null mutant mice. Immunostaining for
      olfactory marker protein revealed the normal presence of fully mature primary
      olfactory neurons within the olfactory neuroepithelium of mutant mice. The axons
      of these neurons form an olfactory nerve, enter the nerve fiber layer of the
      olfactory bulb, and terminate in olfactory glomeruli as in wild-type control
      animals. The olfactory bulb is smaller and the nerve fiber layer is relatively
      thicker in mutants than in wild-type mice. Previous studies have revealed that
      the plant lectin Dolichos biflorus agglutinin (DBA) clearly stains the perikarya
      and axons of a subpopulation of primary olfactory neurons. Thus, DBA staining
      enabled the morphology of the olfactory nerve pathway to be examined at higher
      resolution in both control and mutant animals. Despite a normal spatial pattern
      of DBA-stained neurons within the nasal cavity, there was a distorted axonal
      projection of these neurons onto the surface of the olfactory bulb in N-CAM-180
      null mutants. In particular, DBA-stained axons formed fewer and smaller glomeruli
      in the olfactory bulbs of mutants in comparison to wild-type mice. Many primary
      olfactory axons failed to exit the nerve fiber layer and contribute to glomerular
      formation. These results indicate that N-CAM-180 plays an important role in the
      growth and fasciculation of primary olfactory axons and is essential for normal
      development of olfactory glomeruli.

PMID- 9183744
TI  - Presence of novel N-CAM glycoforms in the rat olfactory system.
AB  - The functional activity of the neural cell adhesion molecule N-CAM can be
      modulated by posttranslational modifications such as glycosylation. For instance,
      the long polysialic acid side chains of N-CAM alter the adhesion properties of
      the protein backbone. In the present study, we identified two novel carbohydrates
      present on N-CAM, NOC-3 and NOC-4. Both carbohydrates were detected on N-CAM
      glycoforms expressed by subpopulations of primary sensory olfactory neurons in
      the rat olfactory system. Based on the expression of NOC-3 and NOC-4 and the
      olfactory marker protein (OMP), four independent subpopulations of primary
      sensory olfactory neurons were characterized. These neurons expressed: both NOC-3
      and NOC-4 but not OMP; both NOC-4 and OMP but not NOC-3; NOC-3, NOC-4, and OMP
      together; and OMP alone. The NOC-3- and NOC-4-expressing neurons were widely
      dispersed in the olfactory neuroepithelium lining the nasal cavity. The axons of
      NOC-4 expressing neurons innervated all glomeruli in the olfactory bulb, whereas
      the NOC-3 expressing axons terminated in a discrete subset of glomeruli scattered
      throughout the whole olfactory bulb. We propose that both NOC-3 and NOC-4 are
      part of a chemical code of olfactory neurons which is used in establishing the
      topography of connections between the olfactory neuroepithelium and the olfactory
      bulb.

PMID- 9183745
TI  - Neurite growth-inhibitory activity in the adult rat cerebral cortical gray
      matter.
AB  - Axon growth-promoting and -inhibitory molecules are likely to work in concert to
      promote and guide axons in vivo. In adult mammals, inhibitory molecules
      associated with myelin in the white matter of the central nervous system (CNS)
      play an important role in the failure of long-distance axon regeneration. The
      presence of neurite growth-inhibitory molecules in the adult rat gray matter has
      not been extensively studied. In this article we describe work on the
      characterization of neurite growth-inhibitory activity in the adult rat cerebral
      cortical gray matter using various biochemical and cell culture approaches. We
      show using a neuronal cell line (NG108-15 cells) that neurite growth-inhibitory
      activity is present in membrane preparations of the cortical gray matter.
      Purified gray matter membranes also induce growth cone collapse of cultured
      embryonic rat dorsal root ganglion neurons. The inhibitory activity in the
      membrane preparations is extractable with 3-[(3-cholamidoprophyl)
      dimethylammonio]-1-propane-sulfonate, but does not appear to be depleted by
      various lectins. Western blots and enzyme treatments showed that the inhibitory
      effect of the gray-matter preparations is not likely to be mediated by myelin
      associated inhibitors or chondroitin sulfate proteoglycans. However, tenascin was
      detected in these samples and may contribute to some of the inhibitory activity.
      Selective separation of the inhibitory molecules can be achieved by ion-exchange
      chromatography, which also suggests the presence of multiple inhibitors in
      cortical gray matter membranes.

PMID- 9183746
TI  - Ethanol influences on the chick embryo spinal cord motor system. II. Effects of
      neuromuscular blockade and period of exposure.
AB  - The study described below was performed as a continuation of a previous study in
      which we found reduced motoneuron number in lumbar spinal cord of the chick
      embryo following chronic ethanol administration from embryonic day 4 (E4) to E11.
      We sought to determine whether this reduction was due to primary ethanol toxicity
      or to enhancement of naturally occurring cell death (NOCD) and to determine
      whether administration of ethanol at a later period of development could also
      reduce motoneuron number. Earlier studies have shown that curare suspends NOCD in
      the chick embryo. By administering both ethanol and curare to these embryos from
      E4 to E11 and examining the lumbar spinal cord on E12, we determined that ethanol
      was directly toxic to motoneurons and reduced motoneuron number in the absence of
      NOCD. By administering ethanol from E10 to E15 and examining the lumbar spinal
      cord on E16, we determined that ethanol can reduce motoneuron number without
      altering spinal cord length during more than one stage of chick embryo
      development, and that ethanol toxicity is not dependent on NOCD. In addition, we
      demonstrated that ethanol does not affect the neurotrophic content of chick
      muscle when it is administered from E10 to E15.

PMID- 9183747
TI  - Immunolocalization of Drosophila eye-specific diacylgylcerol kinase, rdgA, which
      is essential for the maintenance of the photoreceptor.
AB  - The Drosophila retinal degeneration A (rdgA) mutant has photoreceptor cells that
      degenerate within a week after eclosion. The degeneration starts with the
      disruption of the subrhabdomeric cisternae (SRC), which are the organelles
      essential for the transport of phospholipids to the photoreceptive membranes. Our
      previous biochemical and molecular studies suggested that the rdgA gene encodes
      an eye-specific diacylglycerol kinase (DGK). In this study, we show that retinal
      degeneration is prevented by the introduction of the eye-DGK gene in the rdgA
      mutant genome, suggesting that the DGK activity is crucial for the maintenance of
      the photoreceptor. Furthermore, by immunohistochemical analysis, we have
      demonstrated that the rdgA protein is predominantly associated with the SRC,
      suggesting that the conversion from diacylglycerol (DG) to phosphatidic acid (PA)
      most actively occurs in SRC. The analysis of the eyes of mutants homozygous for
      rdgA and eye-protein kinase C mutations indicates that retinal degeneration is
      caused by the deficiency of PA rather than excessive accumulation of DG. From
      these data, we conclude that the production of PA in the SRC membranes is
      essential for the maintenance of the photoreceptor.

PMID- 9183748
TI  - pox-neuro is required for development of chemosensory bristles in Drosophila.
AB  - The gene pox-neuro (poxn), which encodes a possible transcriptional regulator
      including a paired domain, specifies the differences between monoinnervated and
      polyinnervated sensory organs in the embryo. A detailed analysis of this gene,
      and in particular, an analysis of its function in the adult sensory organs, has
      so far been hampered by the unavailability of loss-of-function mutations. Here,
      we report the isolation of loss-of-function mutations of poxn and show that the
      chemosensory bristles are transformed into mechanosensory bristles in mutant
      flies. The external morphology of putative chemosensory bristles, number of
      innervating neurons, and cell division pattern are all affected in the mutants,
      showing that poxn is strictly required for development of the adult chemosensory
      bristles. In addition, the formation of some precursor cells is suppressed in the
      mutants, suggesting that poxn is also required for formation of the precursors of
      chemosensory bristles.

PMID- 9183749
TI  - Immortalization and controlled in vitro differentiation of murine multipotent
      neural crest stem cells.
AB  - To isolate mouse neural crest stem cells, we have generated a rat monoclonal
      antibody to murine neurotrophin receptor (p75). We have immortalized p75+ murine
      neural crest cells by expression of v-myc, and have isolated several clonal cell
      lines. These lines can be maintained in an undifferentiated state, or induced to
      differentiate by changing the culture conditions. One of these cell lines, MONC
      1, is capable of generating peripheral neurons, glia, and melanocytic cells.
      Importantly, most individual MONC-1 cells are multipotent when analyzed at clonal
      density. The neurons that differentiate under standard conditions have an
      autonomic-like phenotype, but under different conditions can express markers of
      other peripheral neuronal lineages. These lines therefore exhibit a similar
      differentiation potential as their normal counterparts. Furthermore, they can be
      genetically modified or generated from mice of different genetic backgrounds,
      providing a useful tool for molecular studies of neural crest development.

PMID- 9183750
TI  - Quality of vision and freedom from optical correction after refractive surgery.

PMID- 9183751
TI  - Steep central islands: have we finally figured them out?

PMID- 9183752
TI  - Posterior chamber silicone phakic intraocular lens.
AB  - BACKGROUND: We investigated the efficacy, safety, and stability of correction
      achieved with a silicone posterior chamber intraocular lens used to correct high
      myopia in phakic eyes. PATIENTS AND METHODS: A silicone posterior chamber plate
      style intraocular lens (Chiron, Adatomed) was implanted in 38 consecutive phakic
      eyes with high myopia (-7.00 to -28.00 diopters (D) over a period of 21 months.
      Follow-up ranged from 3 to 24 months. RESULTS: Three months after surgery,
      refractions in 27 eyes (71%) ranged from -1.00 to +1.00 D and remained stable
      thereafter. Spectacle-corrected visual acuity improved at least two lines in 24
      eyes (63%), and none was lost in any eye. Patient satisfaction was high (92%).
      The few complications that occurred were mostly related to imperfections in the
      surgical technique rather than lack of biocompatibility of the lens. No cataract
      or other vision-threatening complication was present at the end of the study.
      CONCLUSION: This silicone posterior chamber plate-style intraocular lens provides
      a reasonably predictable, safe, and stable means of correcting high myopia.

PMID- 9183753
TI  - Age-related refractive shifts in simple myopia.
AB  - BACKGROUND: An understanding of physiologic age-related shifts in myopic
      refractive errors is important to the refractive surgeon for the interpretation
      of long-term results, surgical planning, and patient counseling. This study
      characterizes the refractive stability of adult simple myopia with a
      retrospective study of 413 eyes. METHODS: Approximately 74,000 patient records
      were analyzed to identify 208 adults with -1.00 to -6.00 diopters (D) of myopia
      who were followed for more than 20 years at the Spokane Eye Clinic. Amounts of
      myopic shift (increase in myopia) and hyperopic shift (decrease in myopia) were
      identified and analyzed within the population. The results were compared to long
      term studies of radial keratotomy. RESULTS: The mean changes per patient age
      decade were: 20s, -0.60 D; 30s, -0.39 D; 40s, -0.29 D; 50s, +0.28 D; 60s, +0.41
      D. Reanalyzed Prospective Evaluation of Radial Keratotomy (PERK) study 10-year
      postoperative data demonstrated progressively increasing hyperopic shifts per
      decade, at least to age 50. CONCLUSION: The normal adult population with simple
      myopia differs from the general population and consists of a population subgroup
      that is relatively stable and other subgroups that experience significant
      refractive shift. The hyperopic shift after radial keratotomy appears to be
      surgically induced and may be larger than previously thought.

PMID- 9183754
TI  - Prevalence of myopia in adults: implications for refractive surgeons.
AB  - BACKGROUND: We reviewed the research on the prevalence of myopia in the adult
      population to compare the refractive distribution of patients being treated with
      excimer laser photorefractive keratectomy to correct myopia, and assess the
      potential market for excimer laser surgery. METHODS: All published reports of
      myopia prevalence in adults were reviewed, as well as the prevalence in the
      Melbourne Visual Impairment Project and the distribution of refractive errors
      treated by the Melbourne Excimer Laser Group in 1994. RESULTS: A large population
      based study of people aged 4 to 74 years in the U.S. showed that 43% had low
      myopia (less than -5.00 diopters (D)), 3.2% had high myopia (-5.01 to -10.00 D),
      and 0.2% had extreme myopia (more than -10.00 D). In Asian populations these
      proportions may be much higher and in African and Pacific island groups, much
      lower. In the Melbourne Visual Impairment Project, we found the prevalence of low
      myopia was 21%, high myopia 2%, and extreme myopia 0.3%. A single excimer laser
      has operated for 3 years in Melbourne. Of those treated, 45% had low myopia, 42%
      high myopia, and 13% extreme myopia. Compared to low myopes, high myopes were ten
      times (OR: 9.8; Confidence interval: 6.69 to 12.91) more likely to have excimer
      laser treatment and extreme myopes were 16 times (OR: 16.40; Confidence interval:
      12.53 to 20.27) more likely. CONCLUSIONS: Although there are many more people
      with lower amounts of myopia in the population and the clinical results have been
      more predictable after one procedure in this group, the perceived benefits of
      excimer laser treatment may be greater for those with higher amounts of myopia,
      thus influencing their decision to undergo excimer laser surgery to correct their
      myopia. There is clearly a large market potential for excimer laser surgery in
      people with low myopia.

PMID- 9183755
TI  - Corneal ablation profilometry and steep central islands.
AB  - BACKGROUND: Photorefractive keratectomy with large diameter ablations using a
      uniform laser beam has produced central undercorrections, or "steep central
      islands" in patients, as seen with videokeratography. METHODS: Using a custom
      optical profilometer to measure corneal ablation profiles and a VISX excimer
      laser system, we measured the effect of ablation algorithms, diameter, depth, and
      dioptric correction on enucleated porcine eyes and living rabbit eyes. Our
      profilometer was verified using a 43.00 diopter (D) spherical surface and a 35.00
      and 43.00 D bicurve test surface as a model for the ablated cornea. RESULTS: The
      profilometer measured the test surfaces to within 3 microns of predicted values.
      Photorefractive keratectomies showed over-ablation peripherally and under
      ablation centrally which increased with ablation diameter and dioptric
      correction. Fixed diameter ablations 2 to 6 mm in diameter and 10 to 80 microns
      deep showed stromal ablation rates vary spatially but not with ablation depth.
      These spatially variant ablation profiles were used to re-engineer the ablation
      algorithm and to produce photorefractive keratectomies with improved sphericity.
      CONCLUSIONS: Steep central islands are caused by the spatial variance of tissue
      ablated with a uniform laser beam irradiance. This aberration can be corrected by
      modifying the laser ablation algorithm to correct for the spatial variance of
      stromal ablation.

PMID- 9183756
TI  - Corneal optical aberrations induced by photorefractive keratectomy.
AB  - BACKGROUND: Photorefractive keratectomy causes marked alteration to anterior
      corneal topography, and is likely to induce major changes to the optical
      aberrations of the eye. METHODS: Six diopters (D) of myopia correction was
      attempted on one eye of 50 patients, randomly allocated to one of three different
      treatments: 5-mm or 6-mm single ablation zone, or a double ablation (multizone; 
      5.00 D correction over 4.6 mm and -1.00 D over 6 mm). Topographic data was used
      to estimate corneal aberration coefficients. These were compared for effect of
      ablation zone, before and 1 year after photorefractive keratectomy. The
      coefficients were used to derive modulation transfer functions for the anterior
      corneal surface. RESULTS: Corneal spherical aberrations and coma-like aberrations
      both increased significantly following photorefractive keratectomy (p < 0.001).
      The mean spherical aberration coefficient increased from 0.36 +/- 0.11 before, to
      0.91 +/- 0.37 after treatment, while the mean coma-like aberration coefficient
      changed from 0.28 +/- 0.16 before, to 0.60 +/- 0.31 after treatment. Ablation
      zone form had a significant effect on spherical aberration (p = 0.030), but not
      for coma (p = 0.96). The spherical aberration coefficient increased least for the
      6-mm ablation (by 0.38 +/- 0.17), compared with the 5-mm ablation (0.69 +/- 0.45)
      and the multizone (0.62 +/- 0.38). Corneal modulation transfer functions were
      reduced significantly following the photorefractive procedure. The effect was
      greatest for large pupil diameters and for spatial frequencies between 2 and 15
      cycles per degree. CONCLUSIONS: Corneal modulation transfer function calculations
      suggest that a significant loss of visual performance should be anticipated
      following photorefractive keratectomy, the effect being greatest for large pupil
      diameters. Results for three ablation zones show that induced aberrations are
      least for the largest (6 mm) ablation zone.

PMID- 9183757
TI  - Improved technique of circular keratotomy for the correction of corneal
      astigmatism.
AB  - BACKGROUND: Based on Gauss' law governing the comparison of hyperbaric pressure
      in the eye and atmospheric pressure, the authors present a procedure to correct
      astigmatism. The present paper describes an improvement of a technique for
      circular keratotomy that was published previously. METHODS: We present data on a
      consecutive series of 32 eyes with a mean corneal astigmatism of 4.66 diopters
      (D) (range -2.25 to -6.00 D) with a variety of clinical diagnoses. The astigmatic
      cornea was trephined with a diameter of 7 mm and a depth of 300 microns. After
      deepening of the trephination with a diamond knife to 550 microns over the
      steeper semimeridians, the intraocular pressure created a rounding of the cornea.
      The amount of astigmatic correction and extent of deepening were controlled
      intraoperatively with a keratoscope. No sutures were placed. RESULTS: In 32
      consecutive eyes, corrections were between 50 and 90% of the initial cylindrical
      values after 1 week to 1 month. In 29 eyes (91%), the results obtained remained
      stable during a 1-year follow-up; in two eyes (6%), the 1-month results worsened
      by more than 1.00 D and in one eye (3%), results improved by more than 1.00 D.
      There were no complications during or after surgery. Wound gaping resulting in
      epithelial plugs did not occur. No patient lost one or more lines of spectacle
      corrected visual acuity, but 13 eyes (40%) gained one or more lines. CONCLUSION:
      The technique of correcting corneal astigmatism by trephining to a depth of 300
      microns, with deepening of the wound to 550 microns along the steep meridian and
      using no sutures can correct up to 10.00 D of astigmatism with reasonable
      stability.

PMID- 9183758
TI  - Comparison of corneal epithelial wound healing after photorefractive keratectomy
      in the rabbit with two types of excimer lasers.
AB  - PURPOSE: To evaluate the differences in epithelial wound healing following
      photorefractive keratectomy when performed with the Summit UV 200 LA and the VISX
      20/20 excimer lasers. METHODS: Sixteen New Zealand rabbits were divided into two
      groups. One group was treated with the Summit laser and the other group treated
      with the VISX 20/20 laser. The treatment consisted of a -6.00 diopter
      photorefractive keratectomy with a 5-mm diameter treatment zone. Epithelial wound
      healing was followed by photography at 4 hour intervals for 64 hours. The length
      of the wound edge and the size, shape, and closure time of the wound were
      measured. RESULTS: The median wound edge length at 4 hours was 18.3 mm for the
      Summit laser and 16.7 mm for the VISX laser. The median wound size at 4 hours was
      22.0 mm2 for the Summit and 21.2 mm2 for the VISX. The median wound closure time
      was 53.4 hours for the Summit laser and 54.0 hours for the VISX laser.
      CONCLUSION: There was no statistically significant difference in the epithelial
      healing of rabbit corneal wounds created by photorefractive keratectomy when
      performed with two current ophthalmic excimer lasers, the Summit UV 200 LA and
      the VISX 20/20.

PMID- 9183759
TI  - Surgical correction of high myopia in phakic eyes with Worst-Fechner myopia
      intraocular lenses.
AB  - BACKGROUND: Implanting an anterior chamber intraocular lens in a phakic eye is an
      effective surgical procedure for the correction of high myopia. However, the
      potential risks on the anterior segment structures are not well-known. We
      conducted a prospective study to evaluate the effectiveness, predictability, and
      safety after Worst-Fechner lenses were implanted to correct high myopia. METHODS:
      We studied 32 eyes with preoperative myopia from -9.50 to -27.00 diopters (D) (
      16.60 +/- 6.29 D). All 32 eyes were studied by clinical specular microscopy, and
      the endothelium was analyzed for cell density. Twenty eyes were additionally
      examined by fluorophotometry for lens transmittance changes. Thirty eyes were
      additionally examined using the flare mode of a laser flare cell photometer for
      anterior chamber inflammation; the patients were divided into three subgroups of
      ten eyes each according to when the postoperative flare measurements were done:
      12 months, 18 months, and 24 months. Thirteen phakic eyes with myopia greater
      than -6.00 D were used as a control group for the flare study. The mean follow-up
      was 18.3 +/- 8 months (range 6 to 24 mo). RESULTS: Fifty-seven per cent of eyes
      (16 of 28) had an uncorrected visual acuity of 20/40 or better 12 months after
      surgery, and 58% (10 of 17 eyes) at 24 months. Spectacle-corrected visual acuity
      improved: 0.15 at 12 months and 0.16 at 24 months (0.1 = one line) from
      preoperative values. Visual acuity was stable after 3 months. Eighty per cent of
      eyes (25 of 31) at 6 months, 75% (21 of 28) at 12 months, and 76.5% (13 of 17) at
      24 months had been correctly planned to within +/-1.00 D of emmetropia. The
      refractive results were stable 3 months after surgery. The mean endothelial cell
      loss was 7.2% at 3 months, 10.6% at 6 months, 13% at 12 months, and 17.6% at 24
      months after surgery. The mean lens transmittance loss was 0.62% at 3 months,
      0.72% at 6 months, 0.82% at 12 months, and 1.03% at 18 months after surgery.
      Flare values were significantly higher for eyes implanted with Worst-Fechner
      lenses than were those of the control group in all periods under consideration
      (Mann-Whitney test, p < 0.05). A decentration greater than 0.5 mm was present in
      43% of eyes (14 of 32), and halos in 56% (18 of 32). In three eyes (9.3%),
      fixation of the lens to the iris was not stable. CONCLUSIONS: Our results for the
      Worst-Fechner myopia lens confirm earlier findings on the effectiveness of the
      refractive results. However, our study showed a continual decrease in endothelial
      cell density, a decrease in lens transmittance, and a chronic subclinical
      inflammation after the implantation of these lenses. Moreover, decentration was
      common, and the fixation of the IOL to the iris was not stable in some eyes.

PMID- 9183760
TI  - The Barraquer Lecture: surgical management of myopia--a clinician's perspective.

PMID- 9183761
TI  - Refractive surgery, optical aberrations, and visual performance.
AB  - Visual optics is taking on new clinical significance. Given that current
      refractive procedures can and do induce large amounts of higher order ocular
      aberration that often affects the patient's daily visual function and quality of
      life, we can no longer relegate the considerations of ocular aberrations to
      academic discussions. Instead, we need to move toward minimizing (not increasing)
      the eye's aberrations at the same time we are correcting the eye's spherical and
      cylindrical refractive error. These are exciting times in refractive surgery,
      which need to be tempered by the fact that after all the research, clinical, and
      marketing dust settles, the level to which we improve the quality of the retinal
      image will be guided by the trade-off between cost and the improvement in the
      quality of life that refractive surgery offers.

PMID- 9183762
TI  - 20/20--how close must we get?

PMID- 9183763
TI  - Asymmetric radial keratotomy for the correction of keratoconus.

PMID- 9183764
TI  - Increased corneal scarring after phototherapeutic keratectomy in Fuchs' corneal
      dystrophy.
AB  - PURPOSE: A 63-year-old female with Fuchs' endothelial corneal dystrophy, stromal
      edema and subepithelial scarring was inappropriately treated with
      phototherapeutic keratectomy, leading to a central focal circular corneal scar
      and decreased visual acuity that required penetrating keratoplasty. METHOD: The
      host corneal button was bisected and fixed in 10% formaldehyde and in
      glutaraldehyde immediately after its removal. RESULTS: Light microscopy
      demonstrated a central area of absent Bowman's layer with a thin layer of
      subepithelial fibrosis, stromal corneal edema, and thickened Descemet's membrane.
      CONCLUSION: Correct estimation of differential ablation rates of tissue and
      shallow, repeated ablations followed by slit-lamp microscopy and/or
      videokeratography help prevent over-treatment.

PMID- 9183766
TI  - Nocardial keratitis after laser in situ keratomileusis.
AB  - PURPOSE AND METHODS: Corneal interface central nodules appeared in a patient who
      underwent uncomplicated laser in situ keratomileusis (LASIK) retreatment for
      residual myopia. RESULTS/CONCLUSIONS: Nocardia asteroides keratitis was confirmed
      by microbiologic studies, which guided treatment. Six months after the appearance
      of the keratitis, the patient's uncorrected visual acuity was 20/45, and
      spectacle-corrected visual acuity was 20/40. The postoperative refraction was
      +0.75 -0.75 X 95 degrees, and slit-lamp examination revealed a clear cornea with
      a mild rounded scar in the central area. Night halos and starbursts were the main
      complaints in this patient. The immediate management of lifting the corneal flap
      for stromal bed scraping, fast microbial identification, and proper treatment was
      the key for the results in this patient.

PMID- 9183765
TI  - Topical diclofenac sodium after excimer laser phototherapeutic keratectomy.
AB  - BACKGROUND: Both the potential analgesic effects and side-effects of topical
      diclofenac sodium 0.1% are points of interest after excimer laser
      phototherapeutic keratectomy. METHODS: Excimer laser phototherapeutic keratectomy
      was performed in 134 eyes of 134 patients. In 65 eyes (65 patients), the effects
      of topical diclofenac given three times a day for 3 to 4 days were compared to a
      control group of 69 eyes (69 patients). All patients received paracetamol for
      systemic analgesia and were patched after surgery until reepithelialization.
      RESULTS: Twenty-eight patients (43%) of the diclofenac group needed additional
      systemic analgesics compared to 67 patients (95%) in the control group. Seventy
      two hours after surgery we found no significant differences in corneal epithelial
      wound healing and no severe complications. CONCLUSION: Topical diclofenac sodium
      reduces postoperative pain in patients after phototherapeutic keratectomy.

PMID- 9183767
TI  - Glycosylated hemoglobin concentration for assessment of glycemic control in
      diabetic cats.
AB  - Blood glycosylated hemoglobin (GHb) concentration was quantified in 84 healthy
      cats, 9 cats with stress-induced hyperglycemia, 37 cats with newly diagnosed
      diabetes mellitus, and 122 diabetic cats treated with insulin or glipizide.
      Diabetic control was classified as good or poor in insulin-treated or glipizide
      treated cats based on review of history, physical examination findings, changes
      in body weight, and measurement of blood glucose concentrations. Blood GHb
      concentration was determined using an affinity chromatography assay. Mean blood
      GHb concentration was similar for healthy normoglycemic cats and cats with
      transient, stress-induced hyperglycemia, but was significantly (P < .001) higher
      in untreated diabetic cats when compared with healthy normoglycemic cats. Mean
      blood GHb concentration was significantly (P < .001) higher in 84 cats with
      poorly controlled diabetes mellitus when compared with 38 cats in which the
      disease was well controlled. Mean blood GHb concentration decreased significantly
      (P < .01) in 6 cats with untreated diabetes mellitus after insulin and dietary
      treatment. A similar significant (P < .01) decrease in mean blood GHb
      concentration occurred in 7 cats with poorly controlled diabetes mellitus after
      diabetic control was improved by an increase in insulin dosage from 1.1 +/- 0.9
      to 1.4 +/- 0.6 U/kg/ 24 h and by feeding a diet containing increased fiber
      content and in 6 cats with transient diabetes mellitus 8.2 +/- 0.6 weeks after
      discontinuing insulin treatment. There was a significant (P < .01) stress-induced
      increase in mean fasting blood glucose concentration and mean blood glucose
      concentration for 12 hours after administration of insulin or glipizide but no
      change in mean blood GHb concentration in 5 docile diabetic cats 12.2 +/- 0.4
      weeks after the cats became fractious as a result of frequent hospitalizations
      and blood samplings. Results of this study suggest that evaluation of blood GHb
      concentration may be a clinically useful tool for monitoring glycemic control of
      diabetes in cats.

PMID- 9183768
TI  - Pathologic factors affecting postsplenectomy survival in dogs.
AB  - The apparently high prevalence of splenomegaly in dogs, along with the surgical
      accessibility of the spleen, results in a relatively large number of
      splenectomies in dogs in clinical veterinary practice. Splenic nodular lesions
      are widely considered to be indicative of hemangiosarcoma and thus a disease that
      is ultimately fatal. This study correlates the results of complete pathologic
      evaluation and classification of 500 spleens obtained by splenectomy with
      survival information for each dog. Among the spleens examined, 257 of 500 (51.4%)
      were classified nonneoplastic and 241 (48.2%) were neoplastic; 2 (0.4%) were
      unclassified. Miscellaneous non-nodular splenomegaly accounted for 46 of 257
      (18%) of the nonneoplastic lesions; nodular splenomegaly accounted for 206 of 257
      (79%) of nonneoplastic splenic lesions and was composed of lymphoid hyperplastic
      nodules and associated hematomas, hyperplastic lymphoid nodules alone, or
      hematomas with no apparent underlying cause. Nodular neoplastic diseases of the
      spleen were divided among benign tumors (11.5%) and a variety of primary
      sarcomas. Hemangiosarcoma made up 51% of splenic malignancies but accounted for
      less than 25% of the spleens evaluated. Survival of dogs with hematomas
      associated with nonneoplastic conditions of the spleen was markedly different
      from that in dogs with hemangiosarcoma-associated hematomas, even though most
      could not be effectively differentiated on gross inspection. Two month
      postoperative survival was 83% for dogs with nonneoplastic-related hematomas,
      whereas only 31% of dogs with hemangiosarcoma, with or without associated
      hematomas, were alive after 2 months. Twelve-month survival times were 64% and
      7%, respectively. An overall postsplenectomy survival rate of 52% was based on
      the number of dogs surviving for a minimum of 6 months postoperatively.

PMID- 9183769
TI  - Effects of glucocorticoid therapy on urine protein-to-creatinine ratios and renal
      morphology in dogs.
AB  - Glomerulonephritis has been associated with exogenous glucocorticoid
      administration and spontaneous hyperadrenocorticism in the dog. The purpose of
      this study was to determine the effects of long-term glucocorticoid therapy on
      urine protein:creatinine ratios (UP/Cs) and renal morphology. Nine young-adult
      male dogs were determined to be healthy and have normal renal function as
      assessed by physical examination, CBC, serum biochemistry analysis, Knott's test
      for Dirofilaria immitis, urinalysis, urine culture, urine protein
      electrophoresis, endogenous creatinine clearance, 24-hour urinary protein
      excretion, and UP/C. Prednisone was administered to each dog at a dosage of 2.2
      mg/kg PO bid for 42 days. Urinalysis and UP/C were performed on days 0, 7, 14,
      21, 28, and 42 of treatment. Mean UP/C on day 0 was 0.29 +/- 0.10. Mean UP/C
      increased progressively to a maximum of 1.27 +/- 1.02 on day 28. Mean UP/C on day
      42 decreased slightly (0.92 +/- 0.56) but remained significantly increased above
      baseline. The most consistent renal light microscopic finding on necropsy
      examination was generalized hypercellular glomerular tufts, suggestive of
      mesangial cell proliferation. Four dogs also had occasional adhesions of
      glomerular tufts to Bowman's capsule, accompanied by thickening of the capsule.
      Direct immunofluorescence for immunoglobulin deposition was negative in all dogs.
      Electron microscopy, evaluated in 7 dogs, was characterized by occasional mild
      segmental thickening of basement membranes, fusion of visceral cell foot
      processes, and glomerular adhesions. The results of this study indicate that long
      term administration of glucocorticoids results in significant proteinuria and
      glomerular changes in the dog.

PMID- 9183771
TI  - Prognosis for neonatal foals in an intensive care unit.
AB  - This study was conducted to develop an equation for the prediction of outcome in
      neonatal foals undergoing treatment in an intensive care unit (ICU). Fifty-three
      physical examination, historical, and clinicopathologic variables were analyzed
      from the records of 99 neonatal foals (< 14 days of age) treated in the neonatal
      ICU of the Equine Medical Center. The outcome was recorded and the results were
      categorized into either surviving or nonsurviving groups. The mean values for the
      2 groups were compared, and variables that differed significantly between the two
      groups were retained and used to construct a logistic regression equation.
      Retained variables were heart rate, temperature, and neutrophil count. The
      predictive equation then was tested prospectively in 2 additional groups of foals
      from 2 separate ICUs. The predicted outcome was compared to the actual outcome,
      and performance variables were calculated. Sensitivity (.83), specificity (.87),
      negative predictive value (.72), and positive predictive value (.93) were
      determined for foals from one neonatal ICU; the sensitivity (.83), specificity
      (.44), negative predictive value (.44), and positive predictive value (.83) were
      lower for foals at a second, separate ICU.

PMID- 9183770
TI  - Platelet hyperfunction in dogs with malignancies.
AB  - In vitro platelet aggregometry was performed on whole blood samples from 59 dogs
      with malignancies and 24 control dogs. Three reagents were used for the
      aggregation studies: collagen, arachidonic acid, and adenosine diphosphate (ADP).
      The parameters measured to evaluate response to collagen included delay in the
      aggregation response, slope of the aggregation curve, maximum aggregation, and
      adenosine triphosphate (ATP) secretion. The platelets of dogs with malignancies
      exhibited significantly (P < .05) shorter delays in the aggregation response,
      higher maximum aggregation, and higher ATP secretion when compared to control
      dogs. For the weaker reagents, ADP and arachidonic acid, the lowest concentration
      resulting in aggregation was determined. Platelets of dogs with malignancies
      tended to aggregate in response to lower concentrations of ADP than did those of
      controls (P < .05). The response of platelets to the concentrations of
      arachidonic acid employed in this study was poor, with few samples achieving
      measurable aggregation. The findings of this study suggest that dogs with
      malignancies have hyperaggregable platelets.

PMID- 9183772
TI  - Systemic arterial dirofilariasis in five dogs.
AB  - Systemic arterial dirofilariasis is an unusual manifestation of heartworm disease
      of dogs that results from aberrant migration of Dirofilaria immitis into the
      peripheral arterial circulation. To expand the clinical characterization of
      systemic arterial dirofilariasis, 5 dogs evaluated at the North Carolina State
      University's College of Veterinary Medicine were reviewed. Common clinical
      presentations included hindlimb lameness, paresthesia of hindlimbs, and
      interdigital ischemic necrosis resulting from thromboembolic disease.
      Visualization of heartworms with angiography or ultrasonography confirmed the
      diagnosis in all cases. All 5 dogs were treated with an adulticide; 3 dogs were
      treated with thiacetasamide sodium and 2 with melarsomine dihydrochloride. Four
      of the 5 dogs survived the initial treatment period; 1 dog died of severe
      thromboembolic complications after thiacatarsamide sodium therapy. The treatment
      of systemic arterial dirofilariasis creates a therapeutic challenge because of
      multiple potential complications resulting from thromboembolic disease.

PMID- 9183773
TI  - Use of ursodeoxycholic acids in a dog with chronic hepatitis: effects on serum
      hepatic tests and endogenous bile acid composition.
AB  - A dog with severe cholestasis secondary to chronic hepatitis was treated with
      ursodeoxycholic acid (UDCA) PO. After 2 weeks of daily treatment, the dog was
      more active and had an improved appetite. Monthly serum biochemical
      determinations and analysis of individual bile acid profiles documented
      improvement in hepatobiliary tests and a marked reduction in the concentrations
      of potentially hepatotoxic endogenous bile acids. These effects were maintained
      for approximately 6 months. The findings in this dog are similar to those
      reported for human patients treated with UDCA and provide preliminary evidence in
      support of its continued evaluation in the treatment of cholestatic liver disease
      in the dog.

PMID- 9183775
TI  - A Turner-like phenotype in a girl with an isodicentric fluorescent Y chromosome
      mosaicism.
AB  - BACKGROUND: The Ullrich-Turner syndrome (UTS) demonstrates a great clinical
      variability according to the cytogenetic and molecular genetic findings in
      various tissues. In few cases the karyotype reveals the presence of an additional
      Y-bearing cell line which is referred to as a borderline case of mixed gonadal
      dysgenesis. In this condition, Turner specific stigmata occur in about half of
      the cases. PATIENT: A 10 year-old girl with short stature and only a few other
      signs of Turner syndrome and hypertrophic clitoris revealed 45,X/46,X,idic(Yq)
      mosaicism with 41% 46,X,idic(Yq) cells in a blood lymphocyte culture. METHODS AND
      RESULTS: Fluorescence in situ hybridisation (FISH) technique, using alpha
      satellite Y-chromosome specific probe for locus DYZ3, confirmed the isodicentric
      character of this structurally abnormal Y chromosome. Polymerase chain reaction
      (PCR) analysis using primers for eight loci along the Y chromosome including SRY
      (Sex determining Region, Y gene) were positive for all loci tested, indicating
      that sequences from the long arm, centromere and most of the short arm of the Y
      chromosome are present. CONCLUSIONS: As patients with normal or rearranged Y
      chromosome have an increased risk of developing gonadal neoplasia prophylactic
      gonadectomy was performed in our patient. No evidence for gonadoblastoma was
      found on her streak-like gonads, but they showed some evidence of tubular
      formation. This paper points out the impact of cytogenetic and molecular genetic
      investigations in the definition of mosaicism in Turner's syndrome.

PMID- 9183774
TI  - Facial palsy and Lyme borreliosis: long-term follow-up of children with
      antibiotically untreated "idiopathic" facial palsy.
AB  - We report on the follow-up of 28 patients, who were admitted to our hospitals
      between 1968 and 1984, and who, at that time, were diagnosed as having idiopathic
      facial palsy. These children were neither tested for Lyme borreliosis (LB) nor
      did they receive antibiotic treatment. In those days LB was an unfamiliar
      infection. Today we can assume that approximately 30%-50% of the patients we
      studied represent actual cases of neuroborreliosis. We, therefore, considered
      them an appropriate model in studying the spontaneous course of LB in children.
      the analysis of the questionnaire designed for our study as well as the
      supplementary clinical and serological reexaminations in some cases provided no
      evidence that neuroborreliosis led to relevant health disorders in any of the
      children (follow-up 10 to 26 years, mean 17). The results of our retrospective
      study led us to conclude that tick-borne facial palsy is relatively benign in
      children and that neuroborreliosis is insignificantly related to late
      complications.

PMID- 9183776
TI  - Application of information technology in clinical diabetes care--a special issue.
      Part 2. Models and education.

PMID- 9183777
TI  - Controlling blood glucose: insights from an engineering control systems
      perspective.
AB  - In order to discern areas of potential improvement in various aspects of
      glycaemic control for patients with insulin dependent (type 1) diabetes mellitus,
      blood glucose control is analysed in the light of general engineering feedback
      control systems theory. This approach is based on models of the system being
      controlled, using appropriate control strategies. The models presently used for
      glycaemic control are analysed from this perspective, revealing certain
      limitations that they impose on the control strategies that use them. Current
      type 1 diabetes regimens are evaluated for the ease with which they may be
      analysed mathematically, suggesting areas where improvements in control may be
      effected by simplifying calculation of appropriate insulin quantities. A new
      model of undergraded insulin action, derived from established insulin action
      profiles, along with a control strategy which flexibly extends the basal/bolus
      regimen using patient-specific parameters, is proposed. This may provide the
      information needed to enable prediction of expected glycaemia several hours into
      the future, thereby enabling earlier corrective action to be taken should it fail
      outside the target range, and in turn potentially reduce the degree and frequency
      of both hyperglycaemia and hypoglycaemia.

PMID- 9183778
TI  - Comparison of parametrized models for computer-based estimation of diabetic
      patient glucose response.
AB  - Two mathematical models for the description of diabetic patient glucose behaviour
      are proposed. Unlike high order differential-equation based compartmental models,
      these models employ only the data typically available to a diabetic patient: the
      history of measured blood glucose concentrations and of insulin injections. The
      model structures are compared with a native benchmark (zero-order hold) model in
      a computer simulation. It is demonstrated that, given four daily blood glucose
      measurements and two daily insulin injections, a parametrized model of patient
      blood glucose response to insulin can provide relevant data in the estimation of
      a patient's future blood glucose response in terms of past blood glucose
      measurements and insulin injections. Parametrized model root means squared errors
      of glycaemic predictions for 18 simulated patients ranged from 7-22 mg dl-1, as
      compared with 19-42 mg dl-1 for the benchmark model.

PMID- 9183779
TI  - Minimal model of food absorption in the gut.
AB  - Of the physiological subsystems involved in glucose metabolism, all have now been
      modelled with continuous-time compartmental models except the gut. To address
      this omission, three progressively more complex models of the conversion of food
      by the gut into the rate of appearance of glucose in plasma were identified,
      using two different sample input foods which were tested on a type 1 diabetic
      patient. The minimal model that achieved a reasonable match with measured values
      had one compartment. Two model parameters specific to the food modelled were
      glycaemic value (grams of glucose per gram of food), and the fractional turnover
      rate, corresponding to a combination of the gastric emptying time constant and
      other rate limiting metabolic processes. Parameters specific to the individual
      were compartmental volumes, specifically for the glucose distribution space. It
      was only possible to achieve an adequate model prediction with a one
      compartmental model by explicitly incorporating transport delay into the model.
      By combining this model with models of insulin production and glucose disposal,
      the glycaemic response of an identified food may also be predicted for patients
      with type 2 diabetes mellitus. This predicted responses, along with the predicted
      response for bread or glucose, enables calculation of the Glycaemic Index for the
      food from its glycaemic value, time constant, and transport delay, along with the
      insulin production and glucose disposal model parameters for the individual
      patient. These three minimal model parameters therefore embody all the
      information of the Glycaemic Index, and more, allowing a continuous prediction of
      the effect of eating a given food over time. Together with a means of combining
      the parameters of individual foods into a combination set for a composite meal,
      this minimal model could enable diabetic patients to predict the time course of
      glycaemic action for a meal and to adjust treatment accordingly.

PMID- 9183780
TI  - Interactive educational simulators in diabetes care.
AB  - Since the Diabetes Control and Complications Trial demonstrated the substantial
      benefits of tight glycaemic control there has been renewed interest in the
      application of information technology (IT) based techniques for improving the day
      to-day care of patients with diabetes mellitus. Computer-based educational
      approaches have a great deal of potential for patients use, and may offer a means
      of training more health-care professionals to deliver such improved care. In this
      article the potential role of IT in diabetes education is reviewed, focusing in
      particular on the application of compartmental models in both computer-based
      interactive simulators and educational video games. Close attention is devoted to
      practical applications-available today-for use by patients, their relatives,
      students and health-care professionals. The novel features and potential benefits
      of such methodologies are highlighted and some of the limitations of currently
      available software are discussed. The need for improved graphical user
      interfaces, and for further efforts to evaluate such programs and demonstrate an
      educational benefit from their use are identified as hurdles to their more
      widespread application. The review concludes with a look to the future and the
      type of modelling features which should be provided in the next generation of
      interactive diabetes simulators and educational video games.

PMID- 9183781
TI  - Educational video game for juvenile diabetes: results of a controlled trial.
AB  - Packy & Marlon, an interactive video game designed to improve self-care among
      children and adolescents with diabetes, was evaluated in a six-month randomized
      controlled trial. In the game, players take the role of animated characters who
      manage their diabetes by monitoring blood glucose, taking insulin injections, and
      choosing foods, while setting out to save a diabetes summer camp from marauding
      rats and mice who have stolen the diabetes supplies. Study participants were
      patients aged 8 to 16 from two separate diabetes clinics. Each participant
      received a Super Nintendo video game system at an initial clinic visit and was
      randomly assigned to receive either Packy & Marlon (treatment group, N = 31) or
      an entertainment video game containing no diabetes-related content (control
      group, N = 28). Participants were interviewed and a parent filled out a
      questionnaire at baseline, three months, and six months. The findings in this
      study indicate that well-designed, educational video games can be effective
      interventions. There was improvement in the treatment group relative to the
      control group in terms of diabetes-related self-efficacy (p = 0.07),
      communication with parents about diabetes (p = 0.025), and self-care behaviours
      (p = 0.003), and a decrease in unscheduled urgent doctor visits (p = 0.08). There
      were no significant differences between the groups in knowledge about diabetes or
      in glycated haemoglobin (HbA1c) levels. Since participants in the study were in
      general well-controlled patients who were receiving excellent medical care,
      future research is contemplated involving youngsters who are not under good
      glycaemic control.

PMID- 9183782
TI  - 'Learning Diabetes'--a multi-media learning package for patients, carers and
      professionals to improve chronic disease management.
AB  - A multi-media program for those with insulin and non-insulin dependent diabetes,
      and for their carers, has been produced. It is delivered on CDROM and contains an
      extensive amount of very high quality generated video of patients using short
      clips (maximum 2 min) totalling 2.5 h in 240 files using MPEG compression. The
      video is combined with a wide range of graphic based activities engaging the user
      in fully interactive processes and allowing them to obtain extensive
      understanding of the disease and to relate to attitudes and perceptions about it
      from those with the same condition. The program is robust and appears to meet the
      educational needs for its extent of interactivity, degree of choice for the user
      and provision of information based on real patient experience. It is easily used
      and modified to meet users of different socio-cultural needs and can be
      translated into different languages. It offers the opportunity not only for
      increased learning and improved self-management of those with diabetes, but also
      greater understanding by those who care for them, both professional and non
      professional. Using the same framework, programs are being developed for other
      chronic diseases including asthma and hypertension.

PMID- 9183783
TI  - Computers in diabetes '96.

PMID- 9183784
TI  - Some approaches to improve bioavailability of peptides and proteins through oral
      and other mucosal routes.
AB  - In this article, an attempt is made to review methods of protein and peptidal
      delivery through oral and non-oral mucosal routes. Strategies that have been or
      are being employed to improve the bioavailability of peptides and proteins
      include alteration of physiological factors by absorption enhancers and enzyme
      inhibitors, modification of native proteins by chemical synthesis of prodrugs and
      analogues and dosage form modifications, e.g. lipid vesicles and emulsions,
      particulate carriers or mucoadhesive polymer systems.

PMID- 9183785
TI  - Synthesis and biological investigations of some novel thiazolylbenzimidazoles,
      and benzimidazolyl-thiazolo[4,5-d]pyrimidines.
AB  - Several thiazolyl-benzimidazoles 2, 4a-c were synthesized through the reaction of
      2-cyanomethyl-1 H-benzimidazole with isothiocyanates followed by cyclization of
      the produced intermediates 1a-b with either ethyl bormocetate or phenacyl
      bromides. When the cyclization was performed in alkaline medium, thiophenyl
      benzimidazoles 5, 6a, b were produced. Another series of thiazolyl-benzimidazoles
      8 a-d was obtained from 2,3-dihydrothiazole-2-(3 H)-thiones 7a-d and 2
      cyanomethyl-1 H-benzimidazole, then cyclized to the corresponding thiazolo[4,5
      d]pyrimidine 10a-d. Most of the prepared compounds were evaluated for their in
      vitro antibacterial, antifungal, anti-HIV and anti-cancer activities. They showed
      promising antifungal activity.

PMID- 9183786
TI  - Synthesis of acyclo-C-nucleosides: 2-(alditol-1-yl)-5-methylthio- and -5
      benzylthio-1,3,4-thiadiazoles.
AB  - Condensation of S-methylhydrazinecarbodithioate or S
      benzylhydrazinecarbodithioate with aldopentoses or aldohexoses gave the
      corresponding aldehydo-sugar S-methylhydrazonecarbodithioates of S
      benzylhydrazonecarbodithioates. Oxidative cyclization of these hydrazones with
      bromine in acetic acid gave the corresponding 2-(alditol-1-yl)-5-alkylthio-1,3,4
      thiadiazoles. Acetylation of the latter gave the corresponding per-O-acetyl
      derivatives which were also obtained by one-pot preparation by treatment of the
      hydrazones with bromine and sodium acetate in acetic acid followed by acetic
      anhydride. Some of the prepared compounds were tested for antimicrobial activity
      against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Candida
      albicans. While hydrazones showed significant activity against these organisms,
      the thiadiazoles were devoid of antimicrobial activity.

PMID- 9183787
TI  - In vitro evaluation of flutamide-carrier systems. Part 1: Preparation and
      evaluation of flutamide systems with polyvinyl pyrrolidone and polyethylene
      glycol 4000 and 6000.
AB  - Coprecipitates were prepared using different ratios of flutamide with polyvinyl
      pyrrolidine (PVP), polyethylene glycol (PEG) 4000 and 6000. Drug solubility in
      carrier solutions, thin layer chromatography (TLC), differential scanning
      calorimetry (DSC), infra-red spectroscopy (IR), uniformity of drug content, drug
      dissolution from its respective systems and effect of aging on the physico
      chemical parameters of stored flutamide-polymer system were studied. PEG 6000 was
      found to be the most efficient polymer in increasing both the solubility and the
      release rate of flutamide. Interaction was found to be complete in certain ratios
      of drug/polymer systems. The dissolution pattern of flutamide from all the
      prepared systems appeared to fit a first order mechanism. Physico-chemical
      parameters of flutamide/carrier systems were not influenced by storage.

PMID- 9183789
TI  - Antiinflammatory activities of procyanidin-containing extracts from Pinus
      pinaster Ait. after oral and cutaneous application.
AB  - Orally in liquid diet administered procyanidin-containing extracts from Pinus
      pinaster Ait. decreased the croton oil-induced ear edema in mice or the compound
      48/80-induced hind paw edema in rats to a statistically significant extent. Most
      effective were the extracts containing mainly oligomeric procyanidins with chain
      lengths greater then 4 units (extracts A or B). Further, the different extracts
      incorporated in various concentrations (1.0, 3.0 or 0.1%) in 5%
      hydroxyethylcellulose gel and applied topically on the shaved back of rats,
      inhibited significantly the ultraviolet radiation-induced increased capillary
      permeability. In these experiments, normalisation of capillary permeability was
      not correlated with the content of the extracts on higher oligomeric
      procyanidins.

PMID- 9183792
TI  - Differential pulse polarographic determination of prazosin hydrochloride in
      tablets.

PMID- 9183793
TI  - HPLC separation of enantiomers of carbisocaine. Study of local anaesthetics, part
      138.

PMID- 9183794
TI  - Development and characterization of nifedipine lipospheres.

PMID- 9183795
TI  - New general formulas for estimation of mean residence time and its variance.

PMID- 9183798
TI  - Protective effect of stobadine on isoproterenol premedicated rabbits.

PMID- 9183797
TI  - Embryotoxicity of 20-hydroxyecdysone and polypodine B from Leuzea carthamoides
      DC.

PMID- 9183799
TI  - Antimicrobial activity of pseudohalogeno(N-salicylidene-alpha-alaninato)cupr
      ates(II).

PMID- 9183800
TI  - Effect of Oxadin on phagocytosis and hydrogen peroxide production.

PMID- 9183801
TI  - Effects of aloin and some structure-related anthracene, anthracenone, and
      anthraquinone derivatives on lipid peroxidation in rat brain cortex homogenates.

PMID- 9183803
TI  - A comparison of fertility control and lethal control of bovine tuberculosis in
      badgers: the impact of perturbation induced transmission.
AB  - In this paper we use mathematical modelling to consider the broad advantages and
      disadvantages of fertility control over lethal control for bovine tuberculosis in
      badger populations. We use a deliberately simple model, attempting to capture
      only the key transmission processes. The model is parametrized with reference to
      the long-term Woodchester Park study. Estimates of mortality rate from this study
      suggest no significant extra mortality risk for animals with evidence of
      infection as indicated by the presence of anti-Mycobacterium bovis antibodies or
      M. bovis isolation. We find that large reductions in prevalence are sometimes the
      consequence of only moderate reductions in population numbers. If we assume that
      the act of control does not in itself affect transmission rates, then as far as
      eradication is concerned, both fertility control and mortality control operate
      through the same epidemiological mechanism, the removal of susceptibles: if one
      is in principle capable of keeping a population low enough to be infection free
      then so is the other. It is necessary to continue either form of control at
      regular intervals to maintain a constant level of infection in the long term. If
      control were to be stopped, return to precontrol levels of badger population and
      infection prevalence would be expected within a few years. Fertility control is
      less effective in reducing population density than lethal control since it can
      only act, at maximum, to remove one age cohort per year. It is also less
      effective in reducing transmission as it can only ever remove susceptibles, while
      lethal control also removes infectious badgers. However, if the social
      disturbance caused by lethal control does in fact increase contact rates for the
      remaining infectious badgers, the relative efficacies of the two strategies
      become a great deal less clear. While we have no quantitative data on the extent
      to which social perturbation does act to promote transmission, model simulations
      show that it is possible to develop plausible scenarios in which the lethal
      control may actually act to increase the absolute numbers of animals infected,
      while reducing the number of uninfected animals to very low numbers.

PMID- 9183804
TI  - Assessment of the haemodynamic response to exercise by means of electrical
      impedance cardiography: method, validation and clinical applications.
AB  - Over the past three decades, the technique of electrical impedance cardiography
      (EIC) has developed into a valid and reliable instrument for the assessment of
      stroke volume. Recent developments have made EIC suitable for routine use during
      exercise testing, too. However, standardization of electrode positioning, stroke
      volume calculation, and data processing is lacking. In our opinion the most
      reliable options are, respectively, a modified semicircular electrode array, the
      Kubicek equation including a haematocrit-based resistivity value, and
      computerized signal averaging. Although EIC derived stroke volume calculation is
      based on several debated assumptions, numerous validation studies have shown good
      accuracy and reproducibility, also during exercise. Addition of EIC measurements
      during standard clinical exercise testing might be of benefit in occupational
      medicine, cardiology and pulmonary medicine. Although in the latter setting no
      validation studies have been performed, major methodological problems are not
      expected.

PMID- 9183805
TI  - Extraction of electrical characteristics from pixels of multifrequency EIT
      images.
AB  - Computer modelling has shown that electrical characteristics of individual pixels
      may be extracted from within multiple-frequency electrical impedance tomography
      (MFEIT) images formed using a reference data set obtained from a purely
      resistive, homogeneous medium. In some applications it is desirable to extract
      the electrical characteristics of individual pixels from images where a purely
      resistive, homogeneous reference data set is not available. One such application
      of the technique of MFEIT is to allow the acquisition of in vivo images using
      reference data sets obtained from a non-homogeneous medium with a reactive
      component. However, the reactive component of the reference data set introduces
      difficulties with the extraction of the true electrical characteristics from the
      image pixels. This study was a preliminary investigation of a technique to
      extract electrical parameters from multifrequency images when the reference data
      set has a reactive component. Unlike the situation in which a homogeneous,
      resistive data set is available, it is not possible to obtain the impedance and
      phase information directly from the image pixel values of the MFEIT images data
      set, as the phase of the reactive reference is not known. The method reported
      here to extract the electrical characteristics (the Cole-Cole plot) initially
      assumes that this phase angle is zero. With this assumption, an impedance
      spectrum can be directly extracted from the image set. To obtain the true Cole
      Cole plot a correction must be applied to account for the inherent rotation of
      the extracted impedance spectrum about the origin, which is a result of the
      assumption. This work shows that the angle of rotation associated with the
      reactive component of the reference data set may be determined using a priori
      knowledge of the distribution of frequencies of the Cole-Cole plot. Using this
      angle of rotation, the true Cole-Cole plot can be obtained from the impedance
      spectrum extracted from the MFEIT image data set. The method was investigated
      using simulated data, both with and without noise, and also for image data
      obtained in vitro. The in vitro studies involved 32 logarithmically spaced
      frequencies from 4 kHz up to 1 MHz and demonstrated that differences between the
      true characteristics and those of the impedance spectrum were reduced
      significantly after application of the correction technique. The differences
      between the extracted parameters and the true values prior to correction were in
      the range from 16% to 70%. Following application of the correction technique the
      differences were reduced to less than 5%. The parameters obtained from the Cole
      Cole plot may be useful as a characterization of the nature and health of the
      imaged tissues.

PMID- 9183806
TI  - Low-frequency ultrasonic velocity measurements in human calcaneal trabecular
      bone.
AB  - Ultrasonic velocities were measured in three orthogonal directions for 17 cubes
      (2 x 2 x 2 cm approximately) of defatted calcaneal trabecular bone using a novel
      pulse transmission method with 37 kHz transducers. Since the wavelength was
      greater than the cross-sectional dimensions of the specimens, it was assumed that
      bar wave propagation was occurring and this allowed Young's modulus to be derived
      from velocity and apparent density. Velocity varied from 1585 +/- 104 m s-1 in
      axis 1 (proximo-distal) to 947 +/- 131 m s-1 in axis 3 (medio-lateral). Thus, the
      velocities measured in axis 3 were considerably lower than those typically seen
      in clinical measurements of the calcaneus. The derived Young's moduli ranged from
      834 +/- 248 MPa (axis 1) to 299 +/- 98 MPa (axis 3), and were comparable in
      magnitude to some previously published data from mechanical testing. The results
      suggest that velocities measured with this technique do indeed correspond to bar
      velocities, and consequently that low-frequency ultrasound can be used to
      directly predict the mechanical properties of trabecular bone specimens in vitro.
      On the other hand, given the marked differences in geometry, wavelengths used and
      the presence of fat, it raises questions about the validity of applying the bar
      wave equation in the context of higher-frequency velocity measurements in the
      intact calcaneus in vivo, despite the fact that this has been found to be useful
      by a number of previous workers. This may require a review of the clinical
      implications of high-frequency ultrasound data.

PMID- 9183807
TI  - Evaluation of an ultrasonic method applied to the measurement of blood
      coagulation time.
AB  - Clinical assessment of the blood clotting mechanism is usually made by measuring
      the time necessary for a sample of plasma to clot. In this work a semi-automatic
      method for measuring coagulation time is evaluated. It employs ultrasound, at 2.7
      MHz, for monitoring variations of the viscosity in a plasma sample undergoing
      coagulation. The evaluation is performed by comparing measurements obtained by
      two well-known methods, the manual tilt tube and the fibrometer, with those
      obtained using the ultrasonic method. A total of 330 plasma samples from
      individuals with normal and altered homeostatic process were analysed. The
      experimental protocol follows two standard tests: the prothrombin time (141
      samples) and the activated partial thromboplastin time (189 samples). The
      agreement between the three different methods is estimated statistically and it
      is shown that all the three can be used interchangeably for clinical purposes.

PMID- 9183808
TI  - Reliability of using the D-max method to define physiological responses to
      incremental exercise testing.
AB  - The purpose of this study was to examine the reliability of using a mathematical
      method, D-max, to define blood lactate kinetics in response to an incremental
      exercise test, and to compare the physiological responses corresponding to the
      workload at D-max with those at the traditional 4 mmol l-1 lactate threshold and
      ventilatory thresholds. Ten male endurance trained athletes, with an average (+/-
      SD) age of 25.6 +/- 8.2 years and maximal oxygen consumption of 64.0 +/- 1.7 ml
      kg-1 min-1, performed an incremental cycling test on two occasions separated by
      four weeks. The expired gas was analysed on-line and plasma lactate concentration
      was analysed for each workload and at exhaustion. The lactate response to
      exercise was represented by a third-order polynomial regression curve. The D-max
      was defined as the point on the regression curve that yields the maximal distance
      to the straight line formed by the two end points of the curve. The results
      demonstrated a high test-retest reliability (intraclass correlation coefficients
      0.77-0.93, p < 0.01) in oxygen consumption, heart rate and exercise intensity at
      both D-max point and exhaustion. No significant differences were found in the
      mean values of the variables between the two tests. It is concluded that the D
      max appears to be a reliable method for defining the individual physiological
      responses to exercise tests, with the advantage of objectivity. However, there is
      no evidence to support the theory that the exercise intensity defined by the D
      max method is superior to that defined by other methods to prescribe training
      intensity or predict aerobic performance for athletes. Further investigations are
      warranted to examine the validity of using this method in exercise prescription.

PMID- 9183809
TI  - Effects of intrastriatal infusion of D2 receptor antisense oligonucleotide on
      apomorphine-induced behaviors in the rat.
AB  - An antisense oligonucleotide strategy was employed to specifically deplete
      postsynaptic striatal D2 receptors in order to determine the possible role of
      presynaptic D2 autoreceptors in mediating behavioral responses induced by low
      doses of apomorphine. A phosphorothioate-modified antisense oligonucleotide
      complementary to the first 19 bases of the coding region of D2 receptor mRNA, a
      scrambled sequence comprising the same bases, or saline was infused bilaterally
      into the striatum of adult rats, twice daily for 2 days via indwelling cannulae.
      After an interval of 8-12 h, rats were habituated and challenged with high (300
      micrograms/kg; subcutaneous) or low (50 micrograms/kg; s.c.) doses of apomorphine
      or its vehicle (0.1% ascorbic acid). Yawning, vacuous chewing mouth movements,
      hypoexploration, and penile grooming induced by low-dose apomorphine were
      unaffected by antisense infusion into the striatum, whereas stereotypic sniffing
      following high-dose apomorphine was markedly suppressed. Intrastriatal infusion
      of antisense resulted in significantly diminished [3H]-raclopride binding, while
      binding of [3H]-SCH 23390 (D1 receptors) and [3H]-WIN 35428 (dopamine
      transporter) was unchanged. D2 mRNA levels determined by quantitative in situ
      hybridization were normal in the striatum and the substantia nigra. Our results
      confirm that stereotypic sniffing is mediated via postsynaptic D2 receptors in
      the striatum, and favor the notion that behavioral responses induced by low doses
      of apomorphine are mediated by presynaptic D2 autoreceptors.

PMID- 9183810
TI  - Transient and persistent consequences of acute stress on long-term potentiation
      (LTP), synaptic efficacy, theta rhythms and bursts in area CA1 of the
      hippocampus.
AB  - Previous studies reported that exposure to an acute stressor of restraint and
      intermittent tailshock impairs long-term potentiation (LTP) in area CA1 of the
      rat hippocampus. In the first experiment, the longevity of the stress-induced
      impairment of LTP was determined. LTP of the excitatory postsynaptic potential
      (EPSP) was impaired 2 but not 4 days after stressor cessation. Exposure to the
      stressor also persistently enhanced the synaptic response to the tetanic
      stimulation patterned after theta rhythm activity (10, 100 Hz bursts delivered at
      5 Hz). In a second experiment, we tested the hypothesis that exposure to the
      stressor enhanced synaptic efficacy itself. EPSPs were recorded from freely
      moving rats before, during and after stressor exposure. The synaptic response was
      not enhanced during stressor exposure. Instead, cessation of the stressor (and
      perhaps movement associated with release from restraint) induced a transient (< 2
      min) decrease in synaptic efficacy. To determine whether exposure to the stressor
      enhances endogenous theta rhythms in area CA1, electroencephalographic (EEG)
      recordings were obtained from freely moving rats before, during and after
      exposure to the stressor. The power of theta (4-8 Hz) and low frequency (0.1-3.9
      Hz) activity was enhanced in response to the tailshock aspect of the stressor.
      Together, the results indicate that exposure to an acute stressful event
      increases theta activity and its cessation transiently decreases synaptic
      efficacy. These transient effects are succeeded by a persistently sensitized
      response to theta burst stimulation and impaired LTP.

PMID- 9183811
TI  - Alterations in striatal dopamine overflow during rotational behavior induced by
      amphetamine, phencyclidine, and MK-801.
AB  - Rats lesioned unilaterally in the medial forebrain bundle with 6-OHDA rotated
      ipsilateral to the lesion following injections of amphetamine, phencyclidine
      (PCP), and MK-801. Concurrent measurement of striatal dopamine (DA) in the intact
      striatum with in vivo microdialysis revealed a dissociation between rotational
      behavior and alterations in DA overflow induced by the three drugs. Amphetamine
      produced robust ipsilateral rotational behavior and a substantial elevation in
      striatal DA (approximately 130% increase at asymptote). PCP produced comparable
      increases in rotational behavior, but only approximately 30% increase in striatal
      DA. MK-801 also had a comparable behavioral effect but failed to alter DA
      overflow in the intact striatum. Since MK-801, a noncompetitive NMDA antagonist
      which does not enhance extracellular dopamine in the striatum, is able to produce
      ipsilateral rotational behavior in rats with unilateral nigrostriatal lesions, it
      is likely that the effects of PCP may also be determined predominantly through
      NMDA blockade in this model.

PMID- 9183812
TI  - NMDA receptors in nucleus accumbens modulate stress-induced dopamine release in
      nucleus accumbens and ventral tegmental area.
AB  - Converging evidence suggests that dopamine (DA) transmission in nucleus accumbens
      (NAcc) is modulated locally by an excitatory amino acid (EAA)-containing input
      possibly originating in medial prefrontal cortex (PFC). In the present study, we
      examined the effects of intra-NAcc administration of EAA receptor antagonists on
      stress-induced increases of NAcc DA levels and of dendritically released DA in
      the ventral tegmental area (VTA). Local injection of the NMDA receptor antagonist
      AP-5 (0.05, 0.5, and 5.0 nmoles)-dose-dependently potentiated increases in NAcc
      DA levels elicited by 15 min of restraint stress. In contrast, local application
      of equivalent doses of the kainate/AMPA receptor antagonist-DNQX-failed to alter
      the NAcc DA stress response reliably. In a separate experiment, we found that
      intra-NAcc injection of AP-5 also potentiated stress-induced increases in VTA DA
      levels. These results indicate that EAAs acting at NMDA receptors in NAcc can
      modulate stress-induced DA release in this region. Our data indicate, however,
      that this action exerts an inhibitory influence on the NAcc DA stress response,
      suggesting that the relevant population of NMDA receptors are not located on NAcc
      DA terminals. The fact that intra-NAcc AP-5 injections also potentiated the DA
      stress response in VTA suggests instead an action mediated by NMDA receptors
      located on NAcc neurons that feedback, directly or indirectly, to cell bodies of
      the mesocorticolimbic DA system.

PMID- 9183813
TI  - Calcitonin gene-related peptide induces the formation of second messengers in
      primary cultures of neonatal rat spinal cord.
AB  - This study investigated second messengers formed in response to calcitonin gene
      related peptide (CGRP) in primary cultures of neonatal rat spinal cord. CGRP
      increased the level of cAMP above basal levels (50 pmol/mg protein) over a large
      range of concentrations. The concentration-response curve had an intermediate
      plateau at 180 pmol cAMP/mg protein in response to 0.01-0.1 nM CGRP and a maximal
      plateau of 850 pmol cAMP/mg protein at 300 nM CGRP. The biphasic concentration
      response curve (EC50S of 0.7 pM and 22 nM) suggests activation of high- and low
      affinity receptors for CGRP. Both neurons and nonneuronal cells contributed to
      the increase in cAMP formation in response to CGRP. The CGRP receptor blocker,
      CGRP8-37, inhibited the response to both 1 and 100 nM CGRP, providing additional
      support for the hypothesis that both high- and low-affinity receptors mediate the
      formation of cAMP. Only a high concentration of CGRP (1 microM) increased the
      formation of cGMP, and CGRP had no effect on the formation of inositol phosphates
      at any of the concentrations tested (0.1-1 microM). These results suggest that
      CGRP-induced responses in the spinal cord are mediated predominately via the
      formation of cAMP. The observation that both neurons and nonneuronal cells
      responded to CGRP indicate that this peptide may have multiple actions in the
      spinal cord.

PMID- 9183814
TI  - Ultrastructural localization of delta-1 opioid receptor in the dorsal raphe
      nucleus of the rat.
AB  - The ultrastructural localization of delta-1 opioid receptor in the rat dorsal
      raphe nucleus was studied by the preembedding avidin-biotin-peroxidase complex
      technique. With application of a low concentration of the first antiserum in
      incubation and control of short-time reaction to 3,3'-diaminobenzidine, the
      immunoreaction seemed to be faint at the light microscopic level. At the electron
      microscopic level, however, delta-1 opioid receptor immunoreaction products were
      found to be localized specifically on the postsynaptic membrane of dendrites,
      dense-cored vesicles, and the surface of the small, clear vesicles in axon
      terminals with strong immunoreactivity. Of the total 659 immunopositive profiles
      observed, up to 62.4% (411/659) were dendrites, whereas 33.8% (223/659) were axon
      terminals. The immunostained myelinated axons and perikarya were relatively rare,
      with the frequencies 0.8% (5/659) and 3.0% (20/659), respectively. Most of the
      immunopositive dendrites (338/411, 82.2%) were immunostained only at the
      postsynaptic membranes. Other immunoreactive dendrites showed their
      immunoreaction products also in some other contents besides the postsynaptic
      membranes (44/411, 10.7%) or only in those contents but not the postsynaptic
      membranes (25/411, 6.1%). Only four dendrites showed their immunoreactive results
      only at the membrane not related to synapse (4/267, 1.0%). No dendrite was found
      immunostained in all the contents. About half of the immunopositive axon
      terminals (125/223, 56.1%) were found to make synapse with nonimmunoreactive
      dendrites (76/223, 34.1%) or immunoreactive dendrites (49/223, 22.0%), while only
      one was found to make contact with immunoreactive perikarya. The present study
      showed that delta-1 opioid receptor in the dorsal raphe nucleus is mostly
      localized on postsynaptic membrane; the main function of the delta-1 receptor in
      the dorsal raphe nucleus is to receive signals from the opioid-containing axon
      terminals through synapses.

PMID- 9183815
TI  - Effects of AMPA and D1 receptor activation on striatal and nigral GABA efflux.
AB  - The ability of locally-administered AMPA and D1 receptor ligands to modulate in
      vivo striatal and nigral GABA efflux was determined in awake, intact male rats
      using a dual-probe microdialysis technique. Intrastriatal perfusion of AMPA (100
      microM) produced a 50-100% increase in striatal GABA efflux that was totally
      blocked by co-perfusion with TTX (10.0 microM). This AMPA-stimulated, TTX
      sensitive GABA efflux was similar across repeated dialsysis perfusions. The
      effects of intrastriatal perfusion of the full D1-like agonist SKF 81297 were
      complex. Perfusion of the higher dose (100 microM) of SKF 81297 enhanced GABA
      efflux, whereas perfusion of the lower dose (10 microM) decreased GABA efflux.
      Both of these effects were blocked by co-perfusion with the D1-like antagonist
      SCH 23390 (10 microM). Intrastriatal perfusion of AMPA (100 microM), SKF 81297
      (100 microM), or AMPA + SKF 81297 did not stimulate GABA efflux in the substantia
      nigra. These bidirectional effects of D1 agonists and the apparent dissociation,
      under certain conditions, between striatal and nigral GABA efflux highlight the
      complexities of DA- and Glu-modulated striatonigral activity in situ.

PMID- 9183816
TI  - Repeated amphetamine administration alters the expression of mRNA for AMPA
      receptor subunits in rat nucleus accumbens and prefrontal cortex.
AB  - Recent evidence suggests that behavioral sensitization to amphetamine is
      associated with alterations in excitatory amino acid (EAA) transmission in
      perikarya (ventral tegmental area) and terminal regions (nucleus accumbens [NAc])
      of the mesoaccumbens dopamine system. The present study determined whether
      repeated amphetamine administration alters expression of mRNAs for AMPA receptor
      subunits. We studied the NAc, because it is the site of expression of amphetamine
      sensitization, and the prefrontal cortex (PFC), because it is the origin of EAA
      projections that regulate the mesoaccumbens dopamine system. Rats were treated
      for 5 days with 5 mg/kg/day amphetamine sulfate or vehicle (controls) and
      perfused 3 or 14 days after the last injection. We used a novel in situ
      hybridization method that allows quantification of mRNA levels [Lu et al. (1996)
      J. Neurosci. Methods, 65:69-76]. Repeated amphetamine administration decreased
      levels of GluR1 and GluR2 but not GluR3 mRNAs in both core and shell subregions
      of the NAc at the 14 day withdrawal time; no changes were observed after 3 days
      of withdrawal. In contrast, levels of GluR1 mRNA in the PFC were increased at 3
      but not 14 days of withdrawal, while GluR2 and 3 mRNAs were unchanged. Levels of
      GluR4 mRNA were very low in both NAc and PFC. Functional properties of
      heteromeric AMPA receptors are determined by subunit composition. Thus, the
      observed changes in mRNAs for AMPA receptor subunits may result in altered AMPA
      transmission in NAc and PFC. This, in turn, may influence the responsiveness of
      the mesoaccumbens DA system to psychomotor stimulants and potentially contribute
      to behavioral sensitization.

PMID- 9183817
TI  - Amphetamine increases the phosphorylation of neuromodulin and synapsin I in rat
      striatal synaptosomes.
AB  - Amphetamine is taken up through the dopamine transporter in nerve terminals and
      enhances the release of dopamine. We previously found that incubation of rat
      striatal synaptosomes increases phosphorylation of the presynaptic neural
      specific protein, neuromodulin (Gnegy et al., Mol. Brain Res. 20:289-293, 1993).
      Using a state-specific antibody, we now demonstrate that incubation of rat
      striatal synaptosomes with amphetamine increases levels of neuromodulin
      phosphorylated at ser41, the protein kinase C substrate site. Phosphorylation was
      maximal at 5 min at 37 degrees C at concentrations from 100 nM to 10 microM
      amphetamine. The effect of amphetamine on the phosphorylation of synapsin I at a
      site specifically phosphorylated by Ca2+/calmodulin-dependent protein kinase II
      (site 3), was examined using a state-specific antibody for site 3-phosphosynapsin
      I. Incubation with concentrations of amphetamine from 1 to 100 nM increased the
      level of site 3-phospho-synapsin I at times from 30 sec to 2 min. The effect of
      amphetamine on synapsin I phosphorylation was blocked by nomifensine. The
      presence of calcium in the incubating buffer was required for amphetamine to
      increase the level of site 3-phospho-synapsin I. The amphetamine-mediated
      increase in the content of phosphoser41-neuromodulin was less sensitive to
      extrasynaptosomal calcium. The amphetamine-mediated increase in the content of
      site 3-phospho-synapsin I persisted in the presence of 10 microM okadaic acid and
      was not significantly altered by D1 or D2 dopamine receptor antagonists.
      Preincubation of striatal synaptosomes with 10 microM of the protein kinase C
      inhibitor, Ro-31-8220, blocked the amphetamine-mediated increases in the levels
      of both phosphoser41-neuromodulin and site 3-phospho-synapsin I. Our results
      demonstrate that amphetamine can alter phosphorylation-related second messenger
      activities in the synaptosome.

PMID- 9183818
TI  - Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after
      selective cholinergic denervation by 192 IgG-saporin.
AB  - A complete and selective destruction of the basal forebrain cholinergic neurons
      projecting to the cerebral cortex and the hippocampus was induced in the rat by
      the toxin 192 IgG-saporin. Using electrophysiologic techniques, we have
      investigated the consequences of this cholinergic denervation on inhibitory and
      excitatory synaptic responses of CA1 pyramidal cells in rat hippocampal slices ex
      vivo. Histochemical experiments were performed in slices from control and 192 IgG
      saporin-treated rats to check the efficacy of the intracerebroventricular
      injection of the immunotoxin. Stimulation of stratum radiatum elicits a
      glutamatergic excitatory postsynaptic potentials followed by a biphasic GABAergic
      inhibitory postsynaptic potential (IPSP). No significant change in IPSP was
      observed in 192 IgG-saporin-treated rats. By contrast, the N-methyl-D-aspartate
      (NMDA) and to a lesser extent the non-NMDA components of the glutamatergic
      response were potentiated in these animals. The possible pre- and postsynaptic
      mechanisms of this potentiation were discussed.

PMID- 9183819
TI  - Nitric oxide synthase inhibition and MPTP-induced toxicity in the common
      marmoset.
AB  - Nitric oxide, produced following activation of N-methyl-D-aspartate (NMDA)
      receptors, may be involved in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      toxicity since NMDA receptor antagonists have been shown to prevent MPTP induced
      nigral cell loss in primates. Common marmosets were treated with either saline or
      MPTP or L-NGnitro arginine methyl ester (L-NAME) or MPTP and L-NAME. MPTP-treated
      common marmosets showed motor deficits including bradykinesia, rigidity, and
      tremor accompanied by a marked loss of tyrosine hydroxylase-immunoreactive
      neurones in the substantia nigra pars compacta and of [3H]-mazindol binding in
      the caudate-putamen. MPTP treatment also caused an increase in glial fibrillary
      acidic protein (GFAP) staining in the substantia nigra compared to controls.
      However, MPTP treatment did not alter the number of constitutive nitric oxide
      synthase-immunoreactive neurones in the caudate-putamen. Furthermore, neurones or
      glial cells immunoreactive for inducible nitric oxide synthase were not observed
      in the substantia nigra pars compacta following MPTP treatment. L-NAME treatment
      alone did not produce any behavioural changes in marmosets and did not alter the
      number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars
      compacta, the number of constitutive nitric oxide synthase-immunoreactive
      neurones or [3H]-mazindol binding in the caudate-putamen compared to saline
      treated control animals. Furthermore, L-NAME did not affect the motor deficits,
      loss of tyrosine hydroxylase-immunoreactive neurones in the substantia nigra pars
      compacta, loss of [3H]-mazindol binding in the caudate-putamen, or the increase
      in GFAP staining in the substantia nigra induced by MPTP treatment of common
      marmosets. The failure of L-NAME to protect against MPTP-induced toxicity in the
      marmoset suggests that nitric oxide does not play a major role in such toxicity
      and casts doubt over the involvement of the NMDA:nitric oxide system in
      neurodegeneration in MPTP-treated primates.

PMID- 9183820
TI  - Atypical location of cannabinoid receptors in white matter areas during rat brain
      development.
AB  - Previous evidence suggests that the endogenous cannabinoid system could emerge
      and be operative early during brain development. In the present study, we have
      explored the distribution of specific binding for cannabinoid receptors in rat
      brain at gestational day 21 (GD21), postnatal days 5 (PND5) and 30 (PND30), and
      at adult age (> 70 days after birth) by using autoradiography with [3H]CP-55,940.
      Our results indicated that specific binding for cannabinoid receptors can be
      detected in the brain of rat fetuses at GD21 in the classic areas that contain
      these receptors in adulthood-in particular, in the cerebellum and the hippocampus
      and, to a lesser extent, in the basal ganglia, several limbic structures, and
      cerebral cortex. The density of cannabinoid receptors in all these structures
      increased progressively at all postnatal ages studied until reaching the
      classical adult values in 70-day-old animals. Interestingly, cannabinoid receptor
      binding can also be detected at GD21 in regions, in which they are scarcely
      distributed or not located in the adult brain and that have the particularity of
      all being enriched in neuronal fibers. Among these were the corpus callosum,
      anterior commissure, stria terminalis, fornix, white matter areas of brainstem,
      and others. This atypical location was quantitatively high at GD21, tended to
      wane at PND5, and practically disappeared at PND30 and in adulthood, with the
      only exception being the anterior commissure, which exhibited a moderate density
      for cannabinoid receptors. Moreover, the binding of [3H]CP-55,940 to cannabinoid
      receptors in the white matter regions at GD21 seems to be functional and involves
      a GTP-binding protein-mediated mechanism. Thus, the activation of these receptors
      with an agonist such as WIN-55,212-2 increased the binding of [35S]-guanylyl-5'-O
      (gamma-thio)-triphosphate, measured by autoradiography, in the corpus callosum
      and white matter areas of brainstem of fetuses at GD21. This increase was
      reversed by coincubation of WIN-55,212-2 with SR141716, a cannabinoid receptor
      antagonist. As this antagonist is specific for the cerebral cannabinoid receptor
      subtype, called CB1, we can assert that the signal found for cannabinoid receptor
      binding in the fetal and early postnatal brain likely corresponds to this
      receptor subtype. Collectively, all these data suggest the existence of a
      transient period of the brain development in the rat, around the last days of the
      fetal period and the first days of postnatal life, in which CB1 receptors appear
      located in neuronal fiber-enriched areas. During this period, CB1 receptors would
      be already functional acting through a GTP-binding protein-mediated mechanism.
      After this transient period, they progressively acquire the pattern of adult
      distribution. All this accounts for a specific role of the endogenous cannabinoid
      system in brain development.

PMID- 9183821
TI  - Nature of the 5' residue in the M2 domain affects function of the human alpha 1
      beta 1 GABAA receptor.
AB  - The effects on the functional properties of the alpha 1 beta 1 GABAA receptor
      when the 5' (alpha 1 Val260; beta 1 Ile255) hydrophobic amino acids in the second
      transmembrane (M2) region were changed to threonine were examined. In response to
      a saturating concentration of GABA, the current evoked in mutant receptors showed
      a decreased rate of desensitization and at equilibrium was a greater fraction of
      the peak current than in wild-type receptors. The half-saturation concentration
      of the peak current response to GABA in mutant receptors was comparable to that
      in wild-type receptors, but the Hill coefficient was reduced to less than one. It
      was concluded that the 5' amino acids in the M2 region have a role in the
      conformational changes that occur within the alpha 1 beta 1 GABAA receptor in
      response to GABA.

PMID- 9183822
TI  - As you like it.
AB  - I have developed something of a reputation for criticizing freely and frequently
      at our meetings and in my writings. You say you like this and find it useful and
      entertaining. As you like it, you are welcome to more of it. My comments and
      criticisms are presented under the following headings: (1) criticize at your
      peril; (2) how it all started (unjustly accused!); (3) abbreviations (a source of
      perennial aggravation, confusion, and waste of time); (4) mysterious bodies in
      mesotheliomas; (5) call a crystal a "crystal," not a "crystalloid"; (6) electron
      microscopy-a study of osmium artifacts; (7) length-to-diameter ratio of
      microvilli (mission impossible); (8) lamellar bodies (a popular but debased
      term); (9) amyloid filaments, not fibers; (10) filaments and microtubules do not
      branch; (11) there is no such thing as pseudomelanosis; (12) botched
      histochemistry (just about every gastrointestinal tract pigment was misdiagnosed
      by histochemistry); (13) intranuclear Russell bodies, not "Dutcher bodies"; and
      (14) nuclear pores and virus-like particles (a new development in an old farce).

PMID- 9183823
TI  - Specificity of intertubular capillary changes: comparative ultrastructural
      studies in renal allografts and native kidneys.
AB  - The pathophysiology of chronic rejection of renal allografts is poorly understood
      and specific morphologic markers are being sought for its diagnosis.
      Ultrastructural splitting and reduplication of the basal lamina of the
      intertubular capillaries (ITCs) have been shown to be consistently associated
      with transplant glomerulopathy (TG) in renal allografts and have been used as a
      marker of chronic allograft rejection. Although the presence of ITC abnormalities
      is extremely helpful diagnostically and has been considered a surrogate for the
      diagnosis of TG when glomeruli are not available for examination, their
      specificity has not been tested. This study examined 135 biopsy specimens from
      renal allografts and native kidneys and categorized the ITC basal lamina
      alterations into 5 patterns. The results showed that although marked ITC basal
      lamina abnormalities are characteristically seen in association with TG, lesser
      degrees of these changes may also be found in native kidneys and in transplants
      with other types of glomerulopathies. In native kidneys, splitting and
      reduplication of the ITC basal lamina were observed in cases of active lupus
      nephritis, membranoproliferative glomerulonephritis type I, crescentic
      glomerulonephritis, cryoglobulinemia, and hypertension. In allografts, ITC
      changes were seen in postinfectious proliferative glomerulonephritis, acute
      cyclosporin toxicity, and hemolytic uremic syndrome, in addition to cases with
      TG. The histopathologic diagnosis in renal diseases relies heavily on clinical,
      immunofluorescence, and ultrastructural findings. Therefore, in the
      transplantation setting, with other less common pathological processes ruled out,
      the presence of abnormalities of the ITC basal lamina is highly indicative of TG.
      This association is particularly true for cases with severe ITC abnormalities.

PMID- 9183824
TI  - Antibody-mediated rejection of human renal allografts: an electron microscopic
      study of peritubular capillaries.
AB  - The role of humoral rejection in acute and chronic rejection of human renal
      allografts other than in hyperacute rejection has not been well established, and
      its importance may be underestimated. Recently, a specific histological pattern
      of antibody-mediated rejection of renal allografts has been recognized. The
      antigens targeted by this mode of rejection are not well defined but are likely
      located on the endothelium of small vessels (arterioles and glomerular and
      peritubular capillaries). In both cellular and humoral rejection, the
      microvasculature of transplanted organs appears to be a main target of injury.
      This study describes the ultrastructural changes of peritubular capillaries, over
      a period of up to 8 months, in 14 biopsy specimens obtained from 5 renal
      allograft recipients diagnosed with "pure" antibody-mediated rejection. In
      peritubular capillaries, there is progression of injury from necrosis of
      endothelial cells with lifting and denudation of basement membrane to complete
      disappearance of capillaries. Acutely, acute tubular necrosis is a constant
      finding. At 2 to 3 months post-transplantation, the remaining capillaries are
      dilated, misshapen, and distorted, and are surrounded by a reduplicated and
      thickened basement membrane. These changes are associated with increased
      interstitial fibrosis and tubular atrophy, comparable to a sort of renal
      "asphyxial" death. The author concludes that in "pure" antibody-mediated
      rejection, the endothelium of peritubular capillaries is a main target of injury.
      The potential role of antibody-mediated rejection in acute and chronic rejection
      of renal allografts needs to be explored further.

PMID- 9183825
TI  - The role of electron microscopy in the diagnosis of nonneoplastic muscle
      diseases.
AB  - Accurate diagnosis of muscle disease is dependent on a careful clinical
      examination followed by the appropriate laboratory investigations, which in a
      contemporary diagnostic center should also include ultrastructural
      investigations. As is the case in other tissues, the interpretation of the
      ultrastructural abnormalities observed in muscle must take into consideration
      several factors, in particular the small sample size, possible artifacts, and the
      nonspecificity of changes. Despite the fact that the majority of ultrastructural
      changes seen in muscle are not specific, electron microscopic examination still
      provides important and unique clues regarding patterns of change that
      characterize certain disease entities. Since this detailed ultrastructural
      information cannot at present be obtained by any other means, it is anticipated
      that electron microscopy will still play a vital role in the diagnosis of the
      nonneoplastic muscle diseases, well into the twenty-first century.

PMID- 9183826
TI  - Reversible ultrastructural alterations in the myocytic mitochondria of isolated
      rat hearts induced by oxygen radicals.
AB  - The present study focuses on reversible mitochondrial ultrastructural alterations
      in myocardial myocytes that correspond or accompany reversible metabolic
      depression observed after oxygen radical exposure. The myocytic mitochondrial
      membranes and matrix of isolated Langendorff-perfused rat hearts were examined by
      semiquantitative morphometry using the electron micrograph as unit. The hearts
      were exposed to either standard perfusion (group A), 10 min of oxygen radicals
      together with superoxide dismutase and catalase followed by 35 min of recovery
      (group B), 10 min of oxygen radicals alone (group C), or 10 min of oxygen
      radicals followed by 35 min of recovery (group D). Mitochondrial ultrastructural
      alterations were detected in only a few micrographs in groups A and B. The
      frequency of micrographs with mitochondrial ultrastructural alterations was 69%
      in group C and 62% in group D. In the group exposed to 10 min of oxygen radicals
      without recovery (group C) condensed pentalaminar membranous profiles arranged in
      parallel, interpreted to be closely adhering cristae, were detected in the
      intracristal compartment of myocytic mitochondria in 50% of the micrographs. The
      cristal adhesions were associated with other mitochondrial ultrastructural
      changes. Cristal adhesions were not present in group A or B, and were rarely
      found in the group exposed to 10 min of oxygen radicals followed by 35 min of
      recovery (group D). Thus, the cristal adhesions appear to be reversible
      alterations caused by exposure to oxygen radicals.

PMID- 9183827
TI  - Silicone breast implants: pathology.
AB  - Questions as to the bioreactivity of silicone breast implants (SBIs) have
      recently been intensely scrutinized, most notably by the media and legal system.
      Pathologists must be aware of the controversy and treat each SBI and associated
      tissue as a potential lawsuit. Grossly, silicone is a clear, viscous substance
      that may be observed either within or extruding from a silastic bag. By light
      microscopy, silicone is a nonstainable, nonpolarizable, refractile substance.
      Thicker sections, especially when viewed by non-Kohler illumination, phase
      contrast, and darkfield microscopy will enhance visualization. Ultrastructurally,
      silicone is an electron-dense, amorphous substance often located within
      phagocytic vacuoles or extracellularly within the stroma. Correlating electron
      probe microanalysis allows for reliable identification. In most cases, a fibrous
      capsule surrounds the SBI, with the interface lining varying from a virtually
      acellular to a synovial-like lining composed of phagocytic and secretory cells.
      Silicone can often be identified within the fibrous capsule and also in distant
      tissues biopsied for suspected autoimmune disorders, such as synovium, skin, and
      lymph nodes, often without ultrastructural evidence of cytologic effects. This
      study has demonstrated that silicone accumulates at distant tissue sites due to
      preexisting inflammation acting as a stimulus. Thus, silicone is not a primary
      inducer of inflammatory disease processes. These findings are supported by
      various large epidemiologic studies.

PMID- 9183828
TI  - The lipofuscin-iron association in pigmentosis tubae.
AB  - Pigmentosis tubae (PT) is a rare condition characterized by the presence of
      numerous lipofuscin-laden macrophages in the lamina propria of the fallopian
      tube. Two women, who also had endometriotic ovarian cysts, showed polypoid
      pigmented tubal mucosae. In addition to lipofuscin, occasional cells showed
      spotty positivity for iron. Ultrastructural examination of the tubal mucosa
      showed the lipofuscin-containing bodies, which were similar to lipofuscin
      containing lysosomes found in other pigmented conditions. Cytoplasmatic ferritin
      and hemosiderin in siderosomes were observed in macrophages and endothelial cells
      of the lamina propria. The present study is the first to demonstrate the presence
      of iron-containing particles and lipofuscin in the residual bodies of PT. The
      origin of the excess iron is not clear, but erythrophagocytosis and an abnormal
      tubal environment could play a role. Iron-promoted lipid peroxidation may alter
      the lysosomal membranes and contribute to the excessive accumulation of
      lipofuscin in these cells.

PMID- 9183829
TI  - Transmission electron microscopic study of the hemorrhagic spots in patients with
      epidemic hemorrhagic fever in the early stage.
AB  - Epidemic hemorrhagic fever (EHF) virus particles were found in the squamous
      epithelial cells and the capillary endothelial cells of the petechial spots
      located on the mucous membrane of the soft palate in 3 patients with severe early
      stage EHF with transmission electron microscopy. The virus particles were round
      or oval in shape, about 100 nm in diameter, with a two-layer lipid envelope from
      which spikes were protruding. The nucleocapsid of the virus appeared to be hollow
      microfilamentoid or dense granules. Meanwhile, budding virus particles with a
      diameter of 80 nm were found in the enlarged Golgi apparatus. The infected cells
      displayed an enlarged and proliferating Golgi apparatus. The morphological
      characteristics of the viron mentioned above coincided with those of the virus
      particles of the family Bunyaviridae. This study is the first to demonstrate that
      the squamous epithelial cells on the mucous membrane of the soft palate are the
      target cells of EHF infection and to provide subcellular morphological evidence
      of petechial hemorrhage at the soft palate.

PMID- 9183830
TI  - Endothelial injury of capillaries in the stria vascularis of guinea pigs treated
      with cisplatin and gentamicin.
AB  - The drugs cisplatin and gentamicin are used for treatment of various cancer
      patients suffering from infection. The authors report a detailed electron
      microscopic study of blood vessels in stria vascularis of guinea pigs after
      treatment with cisplatin alone and in combination with gentamicin. The most
      distinctive features expressing endothelial cellular injury were mitochondrial,
      including occasional paracrystalline inclusions; electron-lucent foci with
      depleted organelles; intracytoplasmic vacuole formations; lipid bodies;
      cytoplasmic extrusions located on the luminal surface; and severe luminal
      constriction of part of the vessels from animals treated with the combined drugs.
      The study suggests that the damage to strial capillaries due to treatment with
      cisplatin alone and in combination with gentamicin may contribute to the
      injurious effects of these drugs on the strial tissue. Furthermore, the results
      of this study may enlarge the awareness of the potential vascular damage and
      vascular complications in additional body systems after medical use of cisplatin
      alone or in combination with gentamicin.

PMID- 9183831
TI  - Primary leiomyosarcoma of brain in an adolescent with common variable
      immunodeficiency syndrome.
AB  - A 14-year-old girl with common variable immunodeficiency syndrome was found to
      have a low-grade malignant neoplasm arising in the left temporal lobe of the
      brain. Ultrastructural and immunohistochemical studies established a diagnosis of
      leiomyosarcoma, despite the rarity of this tumor in children. In situ
      hybridization with the EBER probe revealed essentially all of the neoplastic
      cells to be infected with Epstein-Barr virus (EBV). Children with the acquired
      immunodeficiency syndrome (AIDS) are known to exhibit an increased incidence of
      smooth muscle tumors associated with EBV. Similar tumors have been reported in
      EBV-infected patients undergoing therapeutic immunosuppression. This appears to
      be the first reported case of childhood leiomyosarcoma where the cause of the
      underlying immunodeficiency was a genetic rather than acquired disorder. The
      authors conclude that electron microscopy, immunohistochemistry, and other
      ancillary techniques are essential in the evaluation of unusual tumors in
      immunocompromised children, whether the cause is hereditary or acquired.

PMID- 9183832
TI  - Endocrine carcinoma of the kidney.
AB  - A 4-cm mass in the right kidney of a 43-year-old female had an endocrine
      appearance by light microscopy and electron microscopy confirmed this impression,
      demonstrating the presence of numerous cytoplasmic granules of endocrine caliber.
      Unusual features were patchy immunoreactivity for chromogranin, and polarity of
      the granules within the neoplastic cells. Extrarenal extension and liver
      metastasis were documented.

PMID- 9183833
TI  - Dual differentiation in gastrointestinal stromal tumors.

PMID- 9183834
TI  - Lead sampling.

PMID- 9183835
TI  - Effect of leak location on measured respirator fit.
AB  - A significant difference in leak detection as a function of leak location was
      observed during a study assessing how well current models of quantitative fit
      test systems detect leakage. Known sources of leakage (matched hypodermic
      needles) were introduced at three fixed locations into factory-probed half-mask
      and full-face respirators mounted on a headform-breathing machine system. The
      leak locations were the bridge of the nose, the cheek, and the chin. Baseline
      leakage into each respirator was determined by conducting a fit-test with all
      fixed leak sources capped. Fit tests were repeated with each individual source
      uncapped. Study objectives included determining (1) how well each system measured
      the leakage, and (2) whether leak location had any effect on leak measurement. An
      ambient aerosol fit-test system (Portacount Plus) and a controlled negative
      pressure (CNP) fit-test system (FitTester 3000) were used. The ambient aerosol
      system detected an overall average of 37.2% of the known leakage, with a
      coefficient of variation of 44.7%. An analysis of variance showed significant
      differences in aerosol system measurements of leakage as a function of leak
      location and mask type (p < 0.001). A different pattern of aerosol leak detection
      as a function of leak location was observed between half-mask and full-face
      respirators, which appears to be related to differences in in-mask airflow
      dynamics. The CNP system detected an overall average of 97.9% of the known
      leakage through the same hypodermic needles, with a coefficient of variation of
      4.3%. CNP system results were not affected by leak location (p > 0.43) or mask
      type (p > 0.32).

PMID- 9183836
TI  - Monte Carlo uncertainty analysis of a diffusion model for the assessment of
      halogen gas exposure during dosing of brominators.
AB  - Monte Carlo simulation was incorporated into a diffusion-based exposure
      assessment model for the estimation of worker exposure to halogen gases during
      dosing of 500-lb sacks of a bromine-based biocide (BCDMH) into brominators.
      Indoor and outdoor dosing scenarios were modeled for small and large brominators.
      The diffusion model used describes a concentration gradient of halogen as a
      function of distance and time from the source instead of ascribing worst-case
      single point value estimates to the variables used in the diffusion model. Monte
      Carlo simulation was used to describe a distribution of values for each
      appropriate model variable. Using a personal computer and Monte Carlo simulation
      software, 10,000 iterations of the diffusion model were performed for four
      different dosing scenarios using random and independent samples from the
      distributions entered. The corresponding output distributions of predicted
      exposures were then calculated and displayed graphically for each scenario. The
      results of the Monte Carlo simulation predict that outdoor dosing of either small
      or large brominators with BCDMH is highly unlikely to result in an exceedance of
      the working occupational exposure limit for total halogen. In most ambient wind
      speed conditions, diffusion prevents appreciable airborne exposure to workers in
      the immediate vicinity of the brominator. Although relatively uncommon, dosing of
      brominators indoors in the assumed absence of local exhaust ventilation may
      generate airborne concentrations of total halogen that exceed the working short
      term occupational exposure limit. Although very limited and inconclusive, field
      trial monitoring of BCDMH transfer operations indoors resulted in halogen
      concentrations well within the distribution of concentrations predicted by the
      Monte Carlo simulation of the diffusion model.

PMID- 9183837
TI  - Lactational transfer of volatile chemicals in breast milk.
AB  - Lactational transfer of chemicals to nursing infants is a concern for
      occupational physicians when women who are breast-feeding return to the
      workplace. Some work environments, such as paint shops, have atmospheric
      contamination from volatile organic chemicals (VOCs). Very little is known about
      the extent of exposure a nursing infant may receive from the mother's
      occupational exposure. A physiologically based pharmacokinetic model was
      developed for a lactating woman to estimate the amount of chemical that a nursing
      infant ingests for a given nursing schedule and maternal occupational exposure.
      Human blood/air and milk/air partition coefficients (PCs) were determined for 19
      VOCs. Milk/blood PC values were above 3 for carbon tetrachloride,
      methylchloroform, perchloroethylene, and 1,4-dioxane, while the remaining 16
      chemicals had milk/blood PC values of less than 3. Other model parameters, such
      as solid tissue PC values, metabolic rate constants, blood flow rates, and tissue
      volumes were taken from the literature and incorporated into the lactation model.
      In a simulated exposure of a lactating woman to a threshold limit value
      concentration of an individual chemical, only perchloroethylene,
      bromochloroethane, and 1,4-dioxane exceeded the U.S. Environmental Protection
      Agency non-cancer drinking water ingestion rates for children. Very little data
      exists on the pharmacokinetics of lactational transfer of volatile organics. More
      data are needed before the significance of the nursing exposure pathway can be
      adequately ascertained. Physiologically based pharmacokinetic models can play an
      important role in assessing lactational transfer of chemicals.

PMID- 9183838
TI  - Laboratory comparison of vacuum, OSHA, and HUD sampling methods for lead in
      household dust.
AB  - The goals of this project were to evaluate and compare the efficiency and
      reproducibility of three methods for sampling lead-containing dust in homes. Lead
      containing dust was generated in a 1-m3 chamber and uniformly deposited onto
      surfaces typically found in the home (painted wood, unpainted wood, varnished
      wood, linoleum, and carpet). Trials with three levels of lead concentrations were
      performed for each surface. Replicate, side-by-side, surface samples were
      collected using the Occupational Safety and Health Administration (OSHA) wipe
      method, the Department of Housing and Urban Development (HUD) wipe method, and a
      vacuum-filter method. Samples were digested with nitric acid and analyzed using
      graphite furnace atomic absorption spectroscopy per National Institute of
      Occupational Safety and Health Method 7105. Recovery for the HUD method was
      consistently the highest on most surfaces (linoleum, 89.9 to 108.9%; painted
      wood, 71.2 to 153.7%; unpainted wood, 25.3 to 76.0%; varnished wood, 8.7 to
      165.6%). On carpet the vacuum method had a significantly higher recovery (26.2 to
      47.8%). For all sampling methods the percent recovery depended on type of surface
      and lead concentration. The reproducibility of percent recovery for the HUD
      (pooled coefficient of variation [CV] = 0.22) and OSHA (pooled CV = 0.27) methods
      was lower than that of the vacuum method (pooled CV = 0.46), though not
      statistically significant. Reproducibility for all methods did not vary
      significantly over surface type or lead concentration. Overall, the HUD method
      yielded the most accurate measurements, with recoveries closest to 100%. It was
      also more durable than the OSHA method, where Whatman filters were observed to
      tear.

PMID- 9183839
TI  - Elevated lead contamination in homes of construction workers.
AB  - National Institute for Occupational Safety and Health investigators studied lead
      exposures among 37 families of construction workers; 22 neighborhood families
      with no known lead exposures were included for comparison. Workers were
      identified as having blood lead levels at or above 25 micrograms/dL. This article
      reports the levels of lead contamination on hands and interior surfaces of homes
      and automobiles of study participants. Results indicate that the hands of lead
      exposed workers were seven times more contaminated with lead compared with
      control workers; no difference was found between exposed and control family
      members' hands. Surface lead contamination was significantly higher in
      automobiles driven by the lead-exposed workers; some locations, such as armrests,
      were 10 times more contaminated for the exposed group. High lead loadings in lead
      workers' automobiles were found on the driver's floor (geometric mean [GM] = 1100
      micrograms/m2), driver's armrest (2000 micrograms/m2), and passenger's armrest
      (1200 micrograms/m2). Surface lead concentrations were significantly higher for
      exposed homes compared with control homes in rooms where work clothing was
      changed (GM = 370 versus 120 ppm; p = 0.005). While environmental sources of lead
      were also evaluated, study results strongly suggest that construction workers'
      occupational exposures together with poor hygiene practices were the primary
      causes of lead contamination. Requirements intended to prevent "take-home" lead
      exposures were reported by workers in this study to be infrequently followed by
      employers. These findings may be limited in representativeness since only highly
      exposed workers were selected from a specific geographic area. Regardless,
      targeted education and enforcement efforts are necessary to help ensure that
      preventive measures are adequately practiced throughout the construction
      industry.

PMID- 9183840
TI  - Coping style and situational appraisals as predictors of coping strategies
      following stressful events in sport as a function of gender and skill level.
AB  - The purpose of this study was to examine links between coping style, situational
      appraisals and the subsequent use of coping strategies in response to acute
      stress among competitive Australian basketball players (N = 190, 93 men and 97
      women, ranging in age from 18 to 44 years). Regression analyses indicated that
      participants' approach and avoidance coping responses varied across four sport
      related stressful situations. In addition, both personal and situational factors
      accounted for significant variation in players' approach coping responses, with
      situational factors better predictors of approach coping than personal
      dispositions. For avoidance coping, situational appraisals (i.e. perceived stress
      and controllability) were again better predictors than personal dispositions. The
      results lend credence to the interactional (contextual) model of coping in which
      participants' use of coping strategies is at least a partial function of
      situational demands.

PMID- 9183841
TI  - Stress and blood donation: effects of music and previous donation experience.
AB  - Making a blood donation, especially for first-time donors, can be a stressful
      experience. These feelings of stress may inhibit donors from returning. This
      paper applies stress theory to this particular problem. The effects of a stress
      management intervention (the provision of music) and previous donor experience
      were examined in relation to pre- and post-donation mood, environmental
      appraisals and coping behaviour. Results indicated that the provision of music
      had detrimental effects on environmental appraisals for those who have donated up
      to two times previously, but beneficial effects for those who had donated three
      times before. These effects were, to an extent, moderated by coping processes but
      not perceived control. It is recommended that the provision of music is not used
      as a stress management technique in the context of blood donation.

PMID- 9183842
TI  - Dynamics of behaviour in the Strange Situation: a structural equation approach.
AB  - In this paper, we present a structural equation approach to modelling infant
      behaviour in the Strange Situation. A model was developed on a Dutch data set,
      and was subsequently cross-validated for an American data set containing the
      original Ainsworth data. Model building is reported in some detail as no previous
      similar analyses of the Strange Situation exist in the literature. The latent
      variables in the preferred model are stranger wariness, minimization or
      deactivation of attachment concerns, and maximization or hyperactivation of
      attachment concerns. Stranger wariness influences only the subsequent behaviour
      towards the mother, and behaviour in the second reunion episode is dependent on
      the same mother behaviour in the first reunion episode, and not on other mother
      behaviours. Structural equation modelling behaviour in the Strange Situation is
      shown to provide further insight into the dynamics of the procedure.

PMID- 9183843
TI  - A simple and rapid technique for the immunofluorescence confocal microscopy of
      intact Arabidopsis root tips.
AB  - Visualisation of immunofluorescence labelling of Arabidopsis roots has previously
      been limited to single cell layers. A simple, rapid method has been devised in
      which the whole root can be processed to allow antibody penetration into several
      cell layers. When optically sectioned using confocal microscopy, cellular
      arrangements of microtubules, callose, calmodulin and a phosphoprotein epitope
      have been visualised using this technique. As the root is not physically
      sectioned, information regarding the three-dimensional position of individual
      cells in relation to each other and the tissue as a whole is retained. Using this
      technique, we have assessed the effect of brefeldin A on the frequency of mitotic
      arrays in root tip cortical and epidermal cells, and found that the occurrence of
      phragmoplasts increases significantly with brefeldin A treatment. This study
      demonstrates the possible future use of the whole root technique to assess
      rapidly the developmental, mutational and inhibitor-induced changes in the
      organisation of cellular components in Arabidopsis.

PMID- 9183845
TI  - Ancestral inbreeding only minimally affects inbreeding depression in mammalian
      populations.
AB  - Inbreeding depression can be reduced, or purged, by selection against deleterious
      alleles. This prediction is the basis of the recommendation that captive wildlife
      populations suffering from inbreeding depression be intentionally bred from
      healthy inbred animals. Yet data on the effectiveness of purging inbreeding
      depression are few. In this study I present and use two different regression
      models (an ancestral inbreeding model and a lethal recessive model) to test for
      the presence of purging effects in 25 captive mammalian populations. Fitness
      components examined were neonatal survival, survival from neonate to weaning, and
      litter size. In only one species was purging statistically significant. However,
      15 of 17 species that showed inbreeding depression exhibited a slight decline in
      inbreeding depression in neonatal survival among descendants of inbred animals.
      These results show a small but highly significant trend of purging on neonatal
      survival. No trends in purging effects were observed in weaning survival or
      litter size. The effects were not likely to be strong enough to be of practical
      use in eliminating inbreeding depression.

PMID- 9183844
TI  - Fluorescent in situ hybridization assessment of chromosome copy number in buccal
      mucosal cells.
AB  - Sex chromatin (Barr body) analysis of buccal mucosal cells has been recognized
      for many years as an inexpensive, noninvasive and rapid means of sex
      determination. The conventional Barr body analysis using Papanicolaou stain was
      discontinued as a routine test because of its lack of reliability and its
      inability to detect mosaicism and other chromosomal abnormalities. With the
      advent of recombinant DNA technology and the availability of molecular probes,
      however, the value of this simple albeit obsolete test should be re-evaluated.
      The results of the authors' experience in optimizing a fluorescent in situ
      hybridization (FISH) assay on buccal mucosal cells are described. The utility and
      potential of this assay are explored and discussed.

PMID- 9183846
TI  - Comparisons of genetic variability and genome structure among mosquito strains
      selected for refractoriness to a malaria parasite.
AB  - Restriction fragment length polymorphism (RFLP) markers were used to evaluate
      Aedes aegypti genome structure and genetic variability within and between
      substrains selected for different levels of refractoriness to the malaria
      parasite, Plasmodium gallinaceum. The MOYO-R substrain was previously selected
      for complete refractoriness and the MOYO-IS substrain for intermediate
      susceptibility from the Moyo-In-Dry (MOYO) strain by selective inbreeding (F =
      0.5). Eighteen mapped RFLP markers were used to provide coverage of the mosquito
      genome. The two substrains showed reduced genetic diversity compared with the
      MOYO strain, including significant reductions in mean heterozygosity, number of
      alleles per locus, and proportion of polymorphic loci. Genetic differentiation
      between the two substrains was statistically significant, as reflected by
      differences in allele frequencies. Significant pairwise linkage disequillbrium
      among the RFLP loci was detected in all three strains, most evidently in the MOYO
      strain. This is surprising because the RFLP loci examined are separated by large
      map distances, and therefore linkage disequilibrium should decay to zero after
      many generations of laboratory culture. Our hypothesis to explain this phenomena
      is that lack of recombination, or low recombination rates in some regions of the
      A. aegypti genome, is a result of chromosome inversions. Finally, we used
      graphical genotyping, wherein whole genome genotypic information for individual
      mosquitoes is represented in a simple graphic format, to illustrate genome
      structure and allelic variation within and among the mosquito strains. Our
      analysis revealed an apparent chromosomal deletion on chromosome 3 for some
      individuals in the MOYO strain and MOYO-IS substrain.

PMID- 9183847
TI  - Multiple Mariner transposons in flatworms and hydras are related to those of
      insects.
AB  - Three flatworm species, the freshwater Dugesia tigrina and the marine Stylochus
      zebra and Bdelloura candida, and two freshwater hydra species, Hydra littoralis
      and H. vulgaris, were found to have many distinct representatives of the mariner
      family of transposable elements in their genomes. In several cases the closest
      relatives of these mariners are ones known previously from insect genomes,
      supporting the view that transposons of this family are capable of horizontal
      transfer across phyla, and hence must be capable of functioning in such diverse
      host environments. Twenty other invertebrates representing the major phyla did
      not appear to have mariners of these kinds in their genomes.

PMID- 9183848
TI  - Genetic variation of southern hemisphere fur seals (Arctocephalus spp.):
      investigation of population structure and species identity.
AB  - We have examined phylogenetic and geographic patterns of variation in the
      mitochondrial cytochrome b gene of Southern Hemisphere fur seals (Arctocephalus
      spp.). Our survey of 106 individuals from four putative species reveals three
      distinct patterns of variation reflecting ancient, recent historic, and
      contemporary gene flow. For the combined samples of Subantarctic (Arctocephalus
      tropicalis) and Antarctic (Arctocephalus gazella) fur seals, we find low levels
      of sequence diversity and reciprocal paraphyly of hapiotypes (where
      representative haplotypes of a species are found to occur infrequently in another
      species and vice versa). For the Australian and Cape fur seal subspecies
      (Arctocephalus pusillus doriferus and A. p. pusillus, respectively), we find low
      levels of sequence diversity but significant differences in the regional
      distribution of haplotypes that are consistent with, but not conclusive of, the
      current subspecies definition based on nonmolecular data. For the New Zealand fur
      seal (Arctocephalus forsteri), we find high levels of average sequence diversity
      because of the survival of two divergent lineages of mitochondrial hapiotypes
      with differences approaching that found in interspecific comparisons of other
      mammals. The two divergent clades are distributed sympatrically in some regions,
      but the overall geographic structure of the variation is significant across the
      range of this species. These new molecular data are inconsistent with current
      taxonomic definitions of species within the Southern Hemisphere fur seals and
      argue for reevaluation of these "species" definitions. For management purposes,
      the definition of evolutionarily significant units (Ryder 1986) and genetic
      management units (Moritz 1994) in relation to these species may also be evaluated
      in light of this molecular genetic information.

PMID- 9183849
TI  - Development of a chicken Z-chromosome-specific DNA library.
AB  - We have developed a chicken (Gallus domesticus) Z-chromosome-specific DNA library
      in a phage vector by means of chromosome microisolation and microcloning. The
      chromosomal origin, specificity, and purity was evaluated by fluorescent in situ
      hybridization (FISH) on chicken metaphases. Heterologous chromosome painting
      using this Z-chromosome-specific probe on turkey (Meleagris gallopavo) metaphases
      identified its homologous Z-chromosome, under the same stringent conditions as
      that used in the chicken, indicating a high degree of Z-chromosome sequence
      homology among these two species. This chicken Z-chromosome library will
      facilitate the development of Z-chromosome-specific DNA markers that will be
      useful for genetic mapping in the domestic chicken and related avian species. The
      Z-chromosome-specific DNA probe will also be useful for studies pertaining to the
      sex chromosome evolution in avian species.

PMID- 9183850
TI  - The optical rotator.
AB  - The optical rotator is an unbiased, local stereological principle for estimation
      of cell volume and cell surface area in thick, transparent slabs. The underlying
      principle was first described in 1993 by Kieu & Jensen (J. Microsc. 170, 45-51)
      who also derived an estimator of length. In this study we further discuss the
      methods derived from this principle and present two new local volume estimators.
      The optical rotator benefits from information obtained in all three dimensions in
      thick sections but avoids over-/ underprojection problems at the extremes of the
      cell. Using computer-assisted microscopes the extra measurements demand minimal
      extra effort and make this estimator even more efficient when it comes to
      estimation of individual cell size than many of the previous local estimators. We
      demonstrate the principle of the optical rotator in an example (the cells in the
      dorsal root ganglion of the rat), evaluate its efficiency and compare it with
      other unbiased, local stereological principles available for estimation of cell
      volume and surface area.

PMID- 9183851
TI  - Unbiased stereological estimation of the number and volume of nuclei and nuclear
      size variability in invasive ductal breast carcinomas.
AB  - The application of design-based stereological methods for estimating nuclear
      features quantitatively in invasive ductal breast cancer is described. Nuclear
      number, size and size variability are explored in relation to the tumour grade
      and patient prognosis. The study includes an examination of the efficiency in
      estimating different nuclear volumes, and two different estimators of the nuclear
      size variability are contrasted. Forty-two invasive ductal breast carcinomas
      diagnosed and graded by two pathologists were used. Both 5-microns and 25-microns
      thick sections were obtained from paraffin blocks for stereological study. More
      undifferentiated tumours show significantly larger nuclei than low-grade tumours.
      The estimates based on the disector method demonstrate a decrease in the number
      of tumour cell nuclei per unit volume of tissue from grades 1 to 2 and especially
      from grades 2 to 3. The univariate survival analysis shows a high prognostic
      value of the nuclear volume estimates. The study shows that an efficient sampling
      procedure was performed, particularly when estimating volume-weighted mean
      nuclear volume using the point-sampled intercepts method. This method is more
      efficient than estimation of the number-weighted mean nuclear volume using the
      selector method; however, the latter provides paired estimates of volume- and
      number-weighted mean nuclear volume, as well as an estimate of the coefficient of
      variation of nuclear volume in the number distribution of the same cells.

PMID- 9183852
TI  - Recent applications of the new stereology have thrown fresh light on how the
      human placenta grows and develops its form.
AB  - The availability of design-based stereological methods has made it possible to
      readdress certain key and contentious issues in placental growth and
      morphogenesis. Three particular questions are: (i) does the population of
      cytotrophoblast cells decline during gestation?, (ii) is placental growth
      biphasic or monophasic? and (iii) what are the consequences for intervillous
      porosity of the elaboration of terminal villi? These questions cannot be answered
      definitively without recourse to the new stereology. Applying the disector to
      estimate nuclear number and star volume to assess pore size, recent studies have
      helped to resolve these issues. Their findings are reviewed. Nuclei were counted
      in the trophoblastic epithelium, stroma and vascular endothelium of placental
      villi. It was found that growth is monophasic and proliferative. All types of
      nuclei increased in number throughout gestation and this included
      cytotrophoblast. Trophoblast grows by the continuous recruitment of new
      proliferative units of uniform mean volume. The so-called 'loss' of
      cytotrophoblast cells is a misinterpretation of what is seen on microscopical
      sections and is attributable to disproportionate growth in villous surface area.
      Cells simply become more widely dispersed. Elaboration of finer terminal branches
      on villous trees leads to a decline in the star volumes of villi and intervillous
      pores. Some of the functional implications of these findings are discussed.

PMID- 9183853
TI  - Measuring fractal dimension and complexity--an alternative approach with an
      application.
AB  - Fractal dimension has often been applied as a parameter of complexity, related
      to, for example, surface roughness, or for classifying textures or line patterns.
      Fractal dimension can be estimated statistically, if the pattern is known to be
      self-similar. However, the fractal dimension of more general patterns cannot be
      estimated, even though the concept may be retained to characterize complexity. We
      here show that the usual statistical methods, e.g. the box counting method, are
      not appropriate to measure complexity. A recently developed approach, the
      extended counting method, whose properties are closer to what fractal dimension
      means, is considered here in more detail. The methods are applied to geometric
      and to blood vessel patterns. The weak assumptions about the structure, and the
      lower variance of the estimate, suggest that the extended counting method has
      beneficial properties for comparing complexity of naturally occurring patterns.

PMID- 9183854
TI  - Adaptive differentiations of the skin of the head in a subterranean rodent,
      Spalax ehrenbergi.
AB  - The skin of macroscopically distinct regions (hairy skin, vibrissal fields,
      buccal ridge, and rhinarium) of the head of the blind mole-rat, Spalax
      ehrenbergi, was studied by routine histological methods. Few guard and several
      soft vellus hairs are organized into tufts that grow from a group of hair
      follicles localized in an invaginated compound cavity. We suggest that this hair
      arrangement may be a burrowing adaptation to match frictional resistance. The
      follicles and the compound cavity possess either well developed complex striated
      musculature or errector pili muscles. There are no structural specializations
      (sweat glands, glomus bodies) to enhance thermoregulatory (heat dissipative)
      capacities in the hairy skin of the head. Vibrissae penetrate the epidermal
      surface as single hairs. They are microscopically normally developed and arranged
      in vibrissal fields according to a basal mammalian pattern. Most of them are,
      however, relatively short and inconspicuous. The mystacial vibrissal field is
      horizontally divided by a prominent buccal ridge which is probably involved in
      bulldozing. The hairs in the ridge leave the compound cavity singularly. The
      follicles of guard hairs and bristles are equipped with well developed pilo
      Ruffini complexes indicating that the buccal ridge may serve also as a tactile
      organ. The glabrous skin of the rhinarium has a highly interdigitated dermal
      epidermal interface. The dermal papillae possess simple lamellated and/or simple
      Meissner's corpuscles and few Merkel cell-axon-complexes indicating that the skin
      of the rhinarium may be particularly sensitive to perception of vibrations.

PMID- 9183855
TI  - Detection of corticosteroids in the presence of organic acids in a liquid
      chromatography eluent using the negative-ion mode of thermospray mass
      spectrometry.
AB  - The pKa values of organic acids (HCOOH, CH3CH2COOH, HOCH2COOH, HSCH2COOH and
      FCH2COOH) in a liquid chromatography (LC) eluent mainly influenced the generation
      of adduct ions with corticosteroids. The relative abundance of [M + R] adduct
      ions increased as the pKa value of the organic acid decreased. An interaction
      between the functional groups of the organic acids in the LC eluent and those of
      the corticosteroid affected the generation of fragment ions. When HCOOH was
      present in the mobile phase, the sensitivity to endogenous hydrocortisone and
      cortisone in human urine was maximized.

PMID- 9183856
TI  - Charge reduction of oligonucleotide anions via gas-phase electron transfer to
      xenon cations.
AB  - Multiply-charged anions derived from electrospray (ES) ionization of the
      oligonucleotide 5'-d(GTCTTAGCGCTAAGAC)-3' have been subjected to electron
      transfer reactions with ionized xenon in a quadrupole ion trap and found to
      undergo minimal fragmentation. This observation stands in contrast with electron
      transfer to rare gases from anions of smaller oligonucleotides which have been
      shown to undergo extensive fragmentation. The present results are attributed to
      longer anion lifetimes for the larger oligonucleotide anions (following highly
      exothermic electron transfer) which then allow for collisional cooling by the
      helium bath gas. Reduction to singly charged anions with minimal fragmentation is
      noted, indicating that xenon cations can be considered as a reagent for
      simplifying ES mass spectra of moderately sized oligonucleotides. The relative
      merits of the use of xenon cations in the quadropole ion trap for this purpose is
      discussed.

PMID- 9183857
TI  - Matrix performance in matrix-assisted laser desorption/ionization for molecular
      weight determination in sialyl and non-sialyl oligosaccharide proteins.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry relies on
      the formation of intact molecular ions to determine molecular weight. In
      biochemical research, conventional methods of protein analysis at picomol to
      fentomol sensitivity, such as sodium dodecyl sulphate polyacrylamide gel
      electrophoresis, have been replaced by this new ionization method. Unfortunately,
      problems caused by the mass accuracy and low resolution restrict the use of this
      ionization technique, particularly when a high mass accuracy in a high mass range
      is required. In this paper it is shown that the appropriate choice of parameters
      which determine the desorption/ionization of glycoproteins can improve the
      quality of MALDI mass spectra as well as mass reproducibility and resolution. The
      study of sample-matrix solution composition, pH and instrumental conditions allow
      the molecular weight determination of highly glycosylated proteins with a high
      percentage of sialic acid, e.g. erythropoietin. The glycosylation of this
      molecule which interferes with the production of multiply charged ions in
      electrospray ionization does not affect the desorption/ionization in MALDI
      analysis. We report the best operating conditions used to establish the degree of
      heterogeneity of erythropoietin.

PMID- 9183858
TI  - Microheterogeneity characterization of a paracelsin mixture from Trichoderma
      reesei using high-energy collision-induced dissociation tandem mass spectrometry.
AB  - The microheterogeneity of the paracelsin mixture broth of Trichoderma reesei was
      analysed using mass spectrometric methods, in particular high-energy collision
      induced dissociation (CID) tandem mass spectrometry (MS/MS). Based on the liquid
      secondary ion mass spectrum of the mixture, there are three main components, with
      molecular masses M and (M +/- 14), together with two minor components of
      molecular weight (M +/- 28). The high-energy CID tandem mass spectra of both the
      protonated and sodiated molecules yielded abundant and characteristic fragment
      ions, but of very different types. It was found that a paracelsin peptaibol in a
      mixture could be successfully sequenced based on the tandem mass spectra of its
      protonated and sodiated molecules or, alternatively, on the tandem mass spectra
      of its y7 and b13 fragment ions. A terminology for indicating these sequential
      peptide fragments is proposed. To determine the sequence of new analogues, tandem
      mass spectra of the y7, (y7 +/- 14), b13, (b13 +/- 14) and (MH +/- 14) positive
      ions were also taken. Based on these experiments, four new paracelsin components
      (PA-F, PA-G, PA-H and PA-I) were sequenced successfully. The microheterogeneity
      of the mixture was found to be more pronounced than had been assumed previously.
      In these new analogues, besides positions 6 and 9, position 17 is also involved
      in the exchange. MS/MS studies on minor fragment ions, such as (b13-28) and (b8
      14) show further microheterogeneity at positions 3, 5, 10 and 12, which increase
      the number of possible minor components.

PMID- 9183861
TI  - The dawn of the post-genome era, seen from the ocean front.

PMID- 9183862
TI  - Marine microbial diversity: the tip of the iceberg.
AB  - New techniques for evaluating the biological diversity of naturally occurring
      microbial assemblages combine nucleic-acid-sequencing techniques with molecular
      phylogenetic analysis. These molecular techniques avoid many of the selective
      biases inherent in traditional cultivation-based surveys and provide a universal
      criterion for identifying and relating diverse microbial species. Application of
      the molecular approach in marine environments has revealed the existence of
      unique and previously unrecognized microorganisms. These are providing fresh
      insight into the ecology, evolution and biotechnological potential of the largely
      untapped resource represented by the marine microbial world.

PMID- 9183863
TI  - Crystallinity in starch plastics: consequences for material properties.
AB  - The processing of starches with biodegradable additives has made biodegradable
      plastics suitable for a number of applications. Starch plastics are partially
      crystalline as a result of residual crystallinity and the recrystallization of
      amylose and amylopectin. Such crystallinity is a key determinant of the product's
      properties. This article describes the influence of processing and storage
      conditions on starch crystallinity and offers possible explanations for the
      various properties of starch plastics, in particular for the problems associated
      with ageing, in terms of the different crystalline structures.

PMID- 9183864
TI  - Biomedical applications of nanotechnology--implications for drug targeting and
      gene therapy.
AB  - Colloidal particles in the nanometre size range (less than 1 micron in diameter)
      can be engineered to provide opportunities for the site-specific delivery of
      drugs after injection into the general circulation or lymphatic systems. Targets
      include the liver (both Kupffer cells and hepatocytes), endothelial cells, sites
      of inflammation and lymph nodes. The size and surface of the particle are crucial
      factors in targeting, and the attachment of cell-specific ligands can lead to
      increased selectivity. The applications of such particle engineering are
      discussed in relation to conventional drugs as well as the emerging area of gene
      therapy.

PMID- 9183865
TI  - Peptide nucleic acids: expanding the scope of nucleic acid recognition.
AB  - Peptide nucleic acids (PNAs) are DNA analogs containing neutral amide backbone
      linkages. PNAs are stable to degradation by enzymes and hybridize to
      complementary sequences with higher affinity than analogous DNA oligomers. PNA
      synthesis employs protocols derived from solid-phase peptide synthesis, making
      the methodology straightforward and flexible. PNAs are being incorporated into an
      expanding set of applications, including genome mapping, the identification of
      mutations and measurement of telomere length. The growth in the popularity of
      PNAs as a tool for nucleic acid recognition should accelerate as the properties
      of PNAs become more familiar.

PMID- 9183867
TI  - [National days of laboratory medicine in Russia. Workshop Laboratory medicine:
      Trends and prospects. Moscow, 3-6 June 1997. Abstracts].

PMID- 9183868
TI  - [National days of laboratory medicine in Russia. Workshop: Laboratory medicine:
      Trends and prospects. Moscow, 3-6 June 1997. Abstracts].

PMID- 9183866
TI  - Expanded-bed adsorption in industrial bioprocessing: recent developments.
AB  - Expanded-bed adsorption allows the capture of proteins from particle-containing
      feedstocks without prior removal of particulates, thus enabling clarification of
      a cell suspension or cell homogenate and the concentration of the desired product
      in a single operation. This usually results in higher product recovery in a
      shorter time period. Process development and scale-up of an expanded-bed
      operation is convenient because both the adsorbent and the equipment are similar
      to those in conventional packed-bed chromatography. This article reviews the
      recent developments in expanded-bed adsorption technology and the range of
      applications that are now being achieved.

PMID- 9183869
TI  - [The second breath of transplantation].

PMID- 9183870
TI  - [Surgical treatment of chronic pancreatitis with predominant cephalic involvement
      by double Wirsung duct diversion and restoration of permeability of the cephalic
      duct].
AB  - The aim of this study is to assess the long-term results of an original surgical
      technique for the treatment of patients suffering from painful chronic
      pancreatitis. From 1981 to 1994, 54 patients with chronic painful pancreatitis
      were operated, by means of an original duct drainage procedure, named by the
      authors "double drainage" because it consists of a large transduodenal
      sphincterotomy and a long pancreatic duct, accompanied by repermeabilization of
      the cephalic pancreatic duct. This procedure was used exclusively for type I
      pancreatitis with major lesions in the head of the gland (calcified stones,
      narrowing of the ducts, inflammatory process). There were 40 men and 14 females
      in this series. No perioperative mortality and a low morbidity (22%) were
      observed. Mean follow-up in 52 patients was 56 months (median: 59.5 months). The
      5- year actuarial survival was 85.2% and 81% were free of pain (91% when the
      pancreatic duct was dilated to > 6 mm) versus 63% when the pancreatic duct was (6
      mm) (p < 0.01). These excellent results should serve as a baseline for any
      alternative treatment of this category of painful chronic pancreatitis patients.

PMID- 9183872
TI  - [Contribution of laparoscopic echography in the staging of curative resection of
      cancer of the pancreatic head (26 cases)].
AB  - In a prospective study, 26 patients with pancreatic and peri-ampullary cancer
      were evaluated with ultrasound (US), computerized tomography (CT Scan),
      endoscopic ultra sonography (EUS) and laparoscopic ultrasound (LUS). Sensitivity
      of US and CT scan were comparable, although CT scan seems better to evaluate the
      size of the tumor and for lymph node detection. 50 per cent of patients had a
      criterion for noncurative resection. EUS (16 cases) had the best sensitivity (100
      per cent) for the staging of small tumors (less than 20 millimeters), detection
      of adjacent nodes and the relation between tumor and mesenteric and portal veins.
      EUS was not able to detect peritoneal and/or liver micro-metastases (44 per cent
      of them would be missed by this examination alone). The criterion for noncurative
      resection was 56.6 per cent. LUS exactly assessed all tumors larger than 3
      centimeters (100 per cent). The accuracy compared with endoscopic ultra
      sonography was not as good for small tumors and adjacent nodes, was equal for the
      venous relations with tumors, but better concerning micro-peritoneal or hepatic
      metastasis. The criterion for noncurative resection was 80 per cent. These
      results suggest to use of US and CT as first-line procedures in the pre-operative
      staging and assessment of resectability of pancreatic cancers. When the patient
      does not appear to have disseminated lesions (50 per cent), endoscopic ultra
      sonography gives a good estimation of the size of the tumor, node assessment and
      vascular relations. LES could be the first step for a curative surgical treatment
      LES revealed to discover 15 to 30 per cent of unknown micrometastases and avoided
      useless laparotomy in these patients.

PMID- 9183871
TI  - [Contribution of cancer registries to the evaluation of cancer treatment: on the
      example of rectal cancer].
AB  - Improvement of health care policy requires an assessment of health care
      practices. In France, morbidity registries might be the best tool for such an
      assessment. This study shows how the treatment of rectal cancer can be assessed
      by French cancer registries. Two studies were conducted: a cross-sectional study
      on data from 7 cancer registries in 1990 and a longitudinal study on data from 2
      digestive cancer registries (departments of Calvados and Cote d'Or) between 1978
      and 1990. Finally, we conducted a regional audit concerning quality control in
      rectal resection for cancer in Lower Normandy between 1988 and 1993. In 1990 the
      mean resection rate was 77.8%. The sphincter preservation rate was also
      significantly increased to 53.9% in 1990. The use of adjuvant radiotherapy
      significantly increased between 1978 and 1990, more rapidly in university
      centres. In more recent years, the use of radiotherapy concerned 50% of resected
      rectal cancers with no differences between the various types of health care
      centres. However, in 1990, major geographical variations were observed for the
      use of adjuvant radiotherapy. Similar geographical variations were observed for
      the use of chemotherapy which did not increase with time. Rectal cancers were not
      diagnosed earlier from 1978 to 1990 in the two departments of Calvados and Cote
      d'Or. The use of reproducible quality criteria (length of distal excision, number
      of nodes examined and histological status of lateral margins) showed a global
      deficiency and marked variations between the various types of health care centres
      and levels of surgical training. The french network of French cancer registries
      (FRANCIM) provides accurate and reliable knowledge on medical practices,
      geographical variations, trends and quality control. The potential of cancer
      registries has not been clearly determined, although such information is required
      to plan health care policy.

PMID- 9183873
TI  - [Total pancreatectomy for diffuse and malignant mucinous ductal ectasia of the
      pancreas. Apropos of 2 cases].
AB  - Two cases of mucinous duct ectasia are reported. Epithelial changes were spread
      along the pancreatic duct and ductal ectasia was diffuse. Multi focal
      infiltrating carcinoma was observed in one case, microinvasive carcinoma located
      in the head of the pancreas was observed. Morphologic features by computed
      tomography, endoscopic ultrasonography pancreatography were useful for
      preoperative diagnosis of mucinous pancreatic duct ectasia. In one case,
      malignancy was suggested by measurement of tumor markers in cystic fluid
      aspirated during percutaneous pancreatography. Total duodenopancreatectomy was
      performed in both cases. The two patients were alive and disease-free with a
      follow-up in both cases of 18 and 36 months.

PMID- 9183874
TI  - [Laparoscopic treatment of appendiceal peritonitis in adults].
AB  - The aim of this study was to evaluate the results of laparoscopic treatment of
      appendicular peritonitis. PATIENTS AND METHODS: From January 1991 to December
      1994, 32 patients (16 men and 16 women with a mean age of 43 years) underwent
      emergency laparoscopy for a clinical diagnosis of localized or generalized
      appendicular peritonitis. All patients had double antibiotic therapy for at least
      7 days. The laparoscopic appendectomy technique consisted of:insufflation to 12
      mmHg, introduction of 3 trocars, first peritoneal lavage, coagulation of the
      mesoappendix, ligature of the base of the appendix, no drainage. RESULTS: There
      were 4 conversions (12.5%). Nine of the 28 cases treated completely by
      laparoscopy, presented generalized peritonitis and 19 presented localized
      peritonitis (including 8 abscesses). The operations were performed by 7 surgeons
      and the mean operating time was 86 minutes. There were no deaths. The
      postoperative morbidity was 10.7%. The mean duration of postoperative ileus was
      2.8 days. The mean hospital stay was 6.8 days. Histological examination concluded
      on acute suppurative appendicitis 96.4% of cases. There were no bowel
      obstructions or incisional hernias with a mean followup of 28.5 months.
      CONCLUSIONS: The laparoscopic treatment of appendicular peritonitis is possible,
      simple and reproducible, effective, without any specific complications. The
      advantages of laparoscopic techniques over the traditional large incisions are
      the absence of parietal complications, the quality of exploration and peritoneal
      lavage, and improvement of postoperative comfort.

PMID- 9183875
TI  - [Role of endoscopy in surgery for urinary incontinence].
AB  - In France, approximately 2 or 3 million women suffer from urinary incontinence. A
      consensus has been reached about the safety of treatment of genuine urinary
      stress incontinence by retropubic colposuspension (Burch procedure). The cure
      rate for the abdominal Burch procedure is 85% after 5 years. Since 1991,
      laparoscopic retropubic colposuspension has been advocated for the treatment
      urinary stress incontinence. The procedure can be performed either by
      laparoscopic intraperitoneal or extraperitoneal approaches or by associated
      laparoscopic and vaginal routes. The feasibility of laparoscopic colposuspension
      has been proved. Indeed, a series including 578 patients, showed a
      laparoconversion rate of 3.6%. The most frequent complication of colposuspension
      is bladder injury. The majority of cystotomics were treated laparoscopically. The
      follow-up in this series is relatively short. After one year, the success rate
      was 96%. However, these results must be confirmed by other series with longer
      follow-up and by prospective randomized studies.

PMID- 9183876
TI  - [Vestigial retrorectal cystic formations in adults. Apropos of 3 cases].
AB  - Primary retro-rectal cystic lesions of the adult are malignant or benign
      congenital lesions, with a female predominance. In this report, we present 3
      cases and try to specify the embryologic origin of these lesions and propose an
      anatomopathological classification. The various diagnostic methods are studied.
      Because of infection and risk of malignancy, early complete excision is
      recommended. We suggest the use of a perineal retro-anorectal approach for low
      situated, small cysts.

PMID- 9183877
TI  - [Specific morbidity of substernal goiters. A comparative study with a matched
      series of cervical goiters].
AB  - The operative morbidity rates in patients operated for substernal goiter (SG)
      vary from one series to another. The aim of this study was to reevaluate the
      morbidity using a matched technique. Each SG was matched to a cervical goiter for
      surgical technique, histology and thyroid function. There were 97 SG (75% of
      women), 43% with normal thyroid function, 28% with mild hyperthyroidism, 29% with
      hyperthyroidism. 87% of thyroidectomies were bilateral. Mean age was 66.5 +/-
      11.5 years versus 55.8 +/- 11.9 years for cervical goiters (p < 0.001). The
      percentage of men was higher for SG than for cervical goiter (25% versus 10%, p <
      0.01). Specimen weighed 166 +/- 109g versus 76 +/- 95g (p < 0.0001). Total volume
      of drainage was 164.0 +/- 68 ml versus 123.2 +/- 68 ml (p = 0.003). No operative
      death occurred. Early hypoparathyroidism rate was 3% versus 2% (p = 0.5), and
      late hypoparathyroidism was 1% versus 0% (p = 0.5). There was a 10 mg/l in serum
      calcium post-operative drop in both groups but no change in serum phosphate was
      noted (bilateral thyroidectomies). The early recurrent laryngeal nerve palsy rate
      was 4% versus 0% (p = 0.06) and 3% versus 0% one year later (p = 0.12). Early
      postoperative reoperation rate for hemostasis was 2% versus 1% respectively (p =
      0.25). We conclude that there is no significant difference in surgical morbidity
      between thyroidectomies for SG and cervical goiters when patients are operated in
      specialized centers. Operative fears are not justified.

PMID- 9183878
TI  - [Gastroduodenal arterial aneurysm and chronic pancreatitis. A case and review of
      the literature].
AB  - A case of pseudoaneurysm of the gastroduodenal artery due to chronic pancreatitis
      is reported. Pancreatitis causing splanchnic arterial aneurysm is more likely to
      affect the splenic artery than the gastroduodenal artery. Ten percent of cases of
      chronic pancreatitis are associated with splanchnic aneurysm. Hemorrhage occurs
      in 50% of cases. Color Doppler ultrasound is the best diagnostic tool, indicating
      the need for coeliac arteriography. In our case report, transcatheter
      embolization was performed with stainless steel coils and the pseudoaneurysm was
      successfully occluded.

PMID- 9183879
TI  - [Chronic duodenal obstruction in children. Apropos of a case].

PMID- 9183880
TI  - [Transposition of a skin flap from the nasal dorsum for repair of skin loss on
      the nasal wing. Apropos of 9 clinical cases].
AB  - The authors use a transposition island skin flap from the nasal dorsum for repair
      of the ala nasi. It is a modification of the stalk-flap advocated by Edgerton in
      1967 to augment the columella. The flap is vascularized by branches of the
      anterior ethmoidal artery. The main modifications are;-the size of the flap which
      is 50 mm long and 15 mm wide;-the vascular pedicle is not dissected; this makes
      the flap very reliable;-the outstanding vascularization of this flap is
      corroborated by the fact that, in the same stage, it may be lined with a
      partially composite chondrocutaneous graft. The composite graft is taken from the
      concha and repaired with the Masson procedure. This flap is a very easy procedure
      for alar cutaneous repair for partial alar reconstruction, it is possible to fold
      the flap onto itself after resecting a 2 mm transverse skin strip, making the
      distal extremity a secondary skin island flap which ensures the lining of the
      proximal part. For total alar reconstruction and hemi-rhinoplasty; the flap is
      lined with a composite graft, which allows a one-stage thin reconstruction. The
      flap was used in 9 patients. In one case, there was a total skin necrosis, while
      half of the fasciomuscle layer survived.

PMID- 9183881
TI  - [External canthopexy using the Edgerton-Montandon procedure in lagophthalmos of
      leprosy patients. Technique and indications. Apropos of 30 cases].
AB  - This paper deals with the results observed in 21 ancient leprosy patients
      suffering from lagophthalmos (13 of whom suffered from bilateral lagophthalmos)
      and treated by the Edgerton-Montandon surgical procedure which associates lateral
      canthopexy and tarsorraphy. Eighteen of the 21 treated patients were reviewed at
      one month after the procedure and, overall, results could be evaluated for 30
      eyes. Improvement was noted in all of the 30 eyes and, globally, the residual
      palpebral fissure (during voluntary closing of the eyes by the patient) decreased
      from 6.7 mm before the procedure to 1.8 after the procedure. The following
      recommendations may be proposed. For young patients with intact corneal
      sensation, the Gillies procedure remains the procedure of choice to correct
      lagophthalmos. For older patients with corneal anesthesia, at high risk of
      blindness, the Edgerton-Montandon procedure should be recommended.

PMID- 9183882
TI  - [Natural skin expansion. Applications to the surgery of nevus of the head and
      neck in children].
AB  - The surgical treatment of congenital naevi of the head and neck often require the
      use of expansion prostheses. The high risk of complications in children such as
      infection, necrosis, prosthetic exposure, has led the authors to propose a new
      therapeutic approach, consisting of deferred cutaneous expansion, which uses the
      skin tension as an expansion motor. This allows repair in one or several surgical
      phases, of large defect using the skin of the same anatomical unit, with good
      esthetic results. The authors describe the three main techniques applied to
      surgery of naevi of the head and neck: simple excision-suture, excision-unfolding
      and deforming excision.

PMID- 9183883
TI  - [Value of reduction mammoplasty in the conservative treatment of breast
      neoplasms. Apropos of 70 cases].
AB  - Breast cancer surgery is on the increase. Until now conservative treatment has
      been limited to tumors less than 3 cm; it is now extending to surgery on reduced
      tumors after chemotherapy or radiotherapy. Some cancers still require mastectomy
      because a carcinologic satisfactory tumorectomy would create a major deformity
      not compatible with conservative treatment. It is technically possible to perform
      major tumor resection with good cosmetic results using the reduction mammoplasty
      technique well known in plastic surgery. Between 1983 and 1991, 70 patients were
      treated at Henri Mondor Hospital for breast cancer with breast reduction
      mammoplasty and irradiation. We present the result with an average five years
      follow-up in terms of the cosmetic results relapses and survival rate. The
      actuarial local relapse was less than 10%, the survival with local relapse was
      86% after 5 years, cosmetic results were good in 81% of cases. The association of
      reduction mammoplasty and radiotherapy seems to be a good extension of
      conservative treatment in some large breast tumors.

PMID- 9183884
TI  - [Surgical cover of dorsolumbar radionecrosis. Apropos of 6 cases].
AB  - Thoracolumbar radionecrosis may be difficult to cover. We often use muscular or
      myocutaneus flaps available in this location, mainly the latissimus dorsi flap.
      It can be used as a pedicle, free, or especially a "reversed" flap with lumbar
      pedicles. However in our experience and in the literature this reversed flap is
      difficult to use because of the morbidity of the flap, transposed without its
      main pedicle. The authors consider the current methods of cover by flaps in six
      cases and in the literature. Surgical possibilities are now more numerous. First,
      a latissimus dorsi muscular flap autonomized by vascular delay, half-free flap,
      or a flap with the lengthening of its pedicle is possible. Second, we can also
      use an intercostal island flap for the back and a gluteal thigh flap in the
      lumbar region.

PMID- 9183885
TI  - [Liposuction using a rotary cannula. Technical note].
AB  - The liposuction with a rotary cannula combines suction under traditional
      depression with rotation of the cannula mounted on a hand-piece, connected to a
      motor. This rotation, which can be has high as 400 r.p.m., allows 360 degrees
      treatment of lipodystrophy in a single procedure. Safety is ensured by an
      adjustable couple limiter, which prevents any risk of accidental movements when
      the cannula meets resistance. The authors conducted a study on 2 cases, which
      demonstrated a definite advantage of this technique in marked to severe
      lipodystrophy (1.5 to 7 litres of suction) and in high-density zones which are
      difficult to treat (epigastrium, knees, dorsal folds). This technique does not
      provide any decisive advantages in cases of minor lipodystrophy, which could
      justify its routine use in this context.

PMID- 9183886
TI  - [In situ thrombolysis. Correlation between creatine phosphokinase increase and
      local thrombolysis. An experimental study in the rat].
AB  - This study proposes intraarterial in situ thrombolysis for the treatment of
      microthrombi occurring after tissue crushing. In order to assess the efficacy of
      the thrombolytic, the authors assayed the serum creatine phosphokinase (CPK)
      level in the crushed muscle capillary bed. The action of thrombolytics has now
      been clearly established. In contrast, the correlation between local thrombolysis
      and the serum CPK variation in crush injuries of striated muscle constitutes the
      originality of this paper. This experiment was conducted in twenty Wistar rats in
      which striated muscle crushing was performed. The serum CPK level assayed in
      venous blood, obtained from the capillary bed concerned, before and after local
      thrombolysis. The increased CPK level provided an objective indication of the
      efficacy of intra-arterial thrombolysis after crush injury. The authors now apply
      local thrombolysis according to a prospective clinical protocol for hand
      emergencies associated with a crush mechanism.

PMID- 9183887
TI  - [Microsurgical sutures with non-transfixing staples. An experimental study of 15
      rat aortas].
AB  - This study, conducted in rats, studied a new system of anastomosis, by
      nontransfixing clips, pinching each edge of the artery with minimal trauma.
      Histological examinations were performed at one week and one month in order to
      investigate the vascular wall in the line of anastomosis. Clinical application of
      this procedure was undertaken in view of the encouraging and satisfactory results
      obtained.

PMID- 9183888
TI  - [Internal hemorrhage in abdominal dermolipectomy. 2 reported cases, one of which
      needing emergency surgical repair of aortic fissure].
AB  - The authors report two very exceptional and similar cases. In the first case,
      during abdominal lipectomy, the surgical team was confronted suddenly with an
      internal hemorrhage requiring prompt resuscitation by the anesthetist. Laparatomy
      revealed an aortic fissure, one centimeter above the iliac bifurcation. Bleeding
      was controlled by clamping the aorta, followed by suturing of the fissure.
      Surgery was then completed uneventfully. The second patient developed a
      retroperitoneal hematoma confirmed by postoperative CT scan during lipectomy and
      liposuction. No further treatment was required after control of the hemorrhage.
      No such cases have been reported in the literature and the etiology of these
      cases remains unclear.

PMID- 9183889
TI  - [Functional problems before and after rhinoplasty].
AB  - Rhinoplasties raise relatively specific esthetic problems, but less clearly
      defined functional problems, particularly in the presence of respiratory
      obstructive disorders. Nasal mucosal obstructions are essentially due to
      vasomotor rhinitis (allergic or nonallergic) which becomes chronic. They must be
      controlled medically as they often induce postoperative respiratory distress.
      Structural nasal obstructions (septal, turbinates, valves) essentially raise
      problems of operative indications, particularly for deviated septa. Various
      clinical, radiological, and rhinomanometric criteria allow evaluation of the
      structures involved in the increased nasal resistance, definition of the
      operative indication, selection of the most appropriate surgical technique and
      quantification of the preoperative and postoperative results.

PMID- 9183890
TI  - [Ethics and appearance. Apropos of a most common scheme: plastic surgery, private
      practice, problems and solutions].

PMID- 9183891
TI  - [Current status of the regulation of tissue allografts, role of the French Graft
      Commission].

PMID- 9183892
TI  - [Value of cutaneous allografts in the treatment of severe burns].
AB  - Skin allografts are essential for survival in patients who have suffered major
      third degree burns over more than 50% of the body surface in order to maintain
      covering until autografts from less severely wounded areas can be performed or
      until keratinocyte cultures have grown. Allografts have thus been increasingly
      used for severe burn patients. It has been estimated that 150 m2 are grafted per
      year in France. Both fresh and frozen tissue can be used thanks to the
      organization of graft banks and safe storage.

PMID- 9183893
TI  - [Corneal transplantation].

PMID- 9183894
TI  - [Vascular allografts. Application to the treatment of aorto-iliac prosthetic
      infections with in situ revascularization].

PMID- 9183895
TI  - [Valvular homografts].
AB  - Renewed interest in heart valve homografts is related to recent advances in
      viability. Increased viability is achieved by collecting explanted hearts from
      multi-organ donors and cryopreservation. Right access is usually used in case of
      hereditary cardiopathy to resect or repair the aortic, mitral and tricuspid
      valves. Life-long anticoagulant treatment can thus be avoided. Current mid-term
      and long-term results are very promising.

PMID- 9183896
TI  - [Tissue banks].

PMID- 9183897
TI  - [Retroperitoneal tumors and surgery of the great vessels].
AB  - The great vessels have long been considered as the limiting point for exeresis of
      abdominal tumors. We report eleven retroperitoneal tumors which led to more or
      less extensive vascular involvement. There were two benign tumors (neurofibroma,
      angiolymphoid tumor), 6 primary malignant tumors (liposarcoma, schwannosarcoma,
      corticoadrenal carcinoma, leiomyosarcoma of the inferior vena cava,
      leiomyosarcoma of the aorta, hemangiopericytoma) and 3 secondary malignant tumors
      (melanosarcoma, papillary cystadenocarcinoma, malignant germ cell tumor).
      Vascular surgery included mobilisation of the aorta or vena cava or total
      replacement with a prosthesis. There were no major complications and organ
      resection was limited to that required by tumor invasion. Despite a
      macroscopically satisfactory resection slice in all cases, local recurrence of
      malignant tumors was the rule leading to short term mortality (mean survival 30
      months for primary sarcomas and 35 days for secondary forms). The therapeutic
      decision after careful CT and MRI word-up requires a discussion between the
      radiology, surgery and oncology teams. When the great vessels are involved,
      advice from a vascular surgeon should be acquired.

PMID- 9183898
TI  - [Cystic and papillary tumor of the pancreas: diagnostic and developmental
      uncertainties. Apropos of a case].
AB  - We reported a case of papillary and cystic tumor (Frantz's Tumor) associated with
      familial adenomatous polyposis in a young man, 29 years old. This case emphasized
      the interest of fine needle biopsy and the difficulties for determination of the
      final pathology. Close long term follow up is essential as local recurrencies and
      metastasis in the long term had been recorded, undergoing resection with curative
      intent. Papillary and cystic tumors should be resected.

PMID- 9183899
TI  - [Ambulatory surgery. Organization and results. Apropos of a 5-year experience].
AB  - Ambulatory surgery has been organized and regulated in France since 1991. We
      report the organisation of this activity in our unit and the results in 22,476
      patients. Endoscopies, not specifically surgical, were 25.7% of procedures. Over
      night hospitalization was needed in 3.1% of patients, including about 40% of them
      for social and familial conditions or follow up of diagnosis or therapeutic
      sequences. This rate is growing, because we developed diagnosis or therapeutic
      sequences for interest of the patient. Since 1994, we operated more patients in
      ambulatory surgery than in classical hospitalization.

PMID- 9183900
TI  - [Locoregional anesthesia in children: benefit/risk ratio].
AB  - Efficient and prolonged postoperative analgesia is obtained with regional
      anesthesia in pediatrics. Its wide use has been due to an easy performance in
      pediatrics with a success rate near 100% for the peripheral blocks, and to a
      minimal deleterious hemodynamic effect of the sympathetic block following an
      epidural anesthesia. Regional anesthesia in pediatrics have many indications and
      few contra-indications. In addition the risk of accidents is low and was observed
      mainly with perimedullar blocks.

PMID- 9183901
TI  - [Locoregional anesthesia in obstetrics: benefits and risks].

PMID- 9183902
TI  - [Locoregional anesthesia in digestive surgery].
AB  - Many regional anesthetic techniques can be used in the setting of abdominal
      surgery. Spinal anesthesia has limited indications for lower abdominal surgery
      (below T10), especially abdominal wall surgery and anal surgery. Indications of
      epidural anesthesia are quite similar, while epidural analgesia can be
      extensively used for postoperative analgesia, provided great attention is paid to
      strict monitoring and safety rules. Finally, peripheral regional anesthetic
      techniques are discussed, highlighting their advantages in this particular
      setting.

PMID- 9183903
TI  - [Long-term results of Beger's operation in chronic pancreatitis of cephalic
      predominance].
AB  - Long-term survival (2 to 11 years) in 5 patients who underwent the Beger
      operation for severe, predominantly cephalic chronic pancreatitis showed that
      total pain relief has been achieved in all cases, together with weight gain (2 to
      18 kg) and return to former occupation. In 3 of the 4 patients who did not have a
      concomitant biliary derivation, jaundice (2 cases treated by bile duct-duodenum
      anastomosis) or angiocholitis (1 case) was observed 7, 2 and 3 years after the
      initial operation. These results are better than with classical exeresis or
      derivation. The disadvantage of the procedure is that it is technically
      difficult. In case of a voluminous cystic cavity, the Frey operation should be
      preferred.

PMID- 9183904
TI  - [Neuro-vascular decompression in hemifacial spasm: anatomical,
      electrophysiological and therapeutic results apropos of 100 cases].
AB  - Hemifacial spasm is a neurological disorder due to abnormal hyperactivity of the
      facial nerve. The most common cause of hemifacial spasm is a neuro-vascular
      conflict in the cerebellopontine angle between a vascular loop and the root of
      the facial nerve (96% of cases). Tumors are the cause of hemifacial spasm in only
      1% of cases). The authors present their results in 100 patients who underwent
      microvascular decompression for essential hemifacial spasm between 1990 and 1995.
      They used microsurgical and endoscopic procedures by a minimal retrosigmoid
      approach in all cases. The most common offending vessels were the posterior
      inferior cerebellar artery (70%), the vertebral artery (41%) and the anterior
      inferior cerebellar artery (28%). An aberrant vein was found in 2 cases. There
      were 38% of multiple artery-nerve conflicts. Physiopathology of hemifacial spasm
      is explained by two principal theories: in the ephaptic theory, hyperactivity and
      an abnormal nervous impulse pathway are due to a short demyelinated area on the
      nerve trunk caused by the offending vessel, inducing short circuiting between
      adjacent nerve fibers. In the nuclear theory, hyperactivity of the facial nerve
      is due to an abnormal and automatic activity of the facial nerve nucleus itself,
      induced by the vessel. The authors used pre and postoperative electromyographic
      tests and intraoperative electromyographic tests. Their results tend to prove the
      nuclear theory. Ninety per cent of the patients had a good result, with a mean
      follow-up time of 30 months in 60 cases. In 82% of the cases, there was a total
      recovery after a single procedure. There was no mortality and no facial palsy.
      Hearing loss occurred in less than 5%.

PMID- 9183905
TI  - [Prognostic value of electroneuronography and trigemino-facial reflex in Bell's
      palsy].
AB  - 56 patients with Bell's palsy were tested with electroneuronography (ENoG and
      Blink reflex (BR) within the 5th and 15th day of onset of facial paralysis. The
      recovery at the end of evolution was evaluated with the study of facial function.
      This retrospective study showed that ENoG is able to predict with a very low risk
      of error a good prognosis when more than 10 percent (strictly, of fibers (non
      degenerated and blocked) are active. On the other hand only persistence or early
      recovery of BR can assure a good prognosis whereas the absence do not permit to
      conclude.

PMID- 9183906
TI  - [Failures after tympanoplasty].
AB  - Failures and pitfalls in chronic ear surgery have been studied. The material
      consists of a retrospective study of 616 cases of tympanoplasty. The results were
      mainly analysed into cases of iatrogenic cholesteatoma (23), labyrinthine
      fistulae (25) and disruption of ossicular chain (46). The incidence of fistula
      into the semi-circular canal is high with cholesteatoma, and careful removal of
      the matrix is recommended to prevent sensorineural hearing loss. Disarticulation
      of the incudo-stapedial joint is performed to eradicate attic cholesteatoma and
      protect the cochlea. However, this procedure gives a risk of damage to the inner
      ear. The frequency and nature of sensorineural losses following chronic ear
      surgery have been discussed. Surgical precautions are advocated to prevent inner
      ear damage or other iatrogenic complications.

PMID- 9183907
TI  - [Role of super selective arteriography with embolization in the treatment of
      severe epistaxis: our experience apropos of 16 cases].
AB  - Diagnostic angiography and super selective embolization of the internal maxillary
      artery were performed on 16 cases between 1990 and 1995. The patients (mean age,
      49 years) were treated for severe posterior epistaxis, refractory to local
      haemostatic therapy (nasal packing alone for the most of them), hypertension was
      found to be the most frequent predisposing factor, 13 patients had their nose
      bleeding stopped. Among the 3 failures, were 2 cases of Osler-Weber-Rendu
      disease, which were subsequently significatively improved by this method. We
      conclude that angiography with super selective embolization is considered as a
      valuable diagnostic and therapeutic option in the management of patients with
      severe epistaxis.

PMID- 9183908
TI  - [Our experience on Rendu-Osler disease. Apropos of 19 cases].
AB  - We report a synthesis of our experience about the Osler-Weber-Rendu disease,
      based on a retrospective study of 19 cases collected from 1978 to 1995. Except
      the almost systematic recourse to anterior or posterior packings in 31% of cases,
      management of epistaxis in urgency has consisted of arteriography with
      embolization of the maxillary arteries. In this way, in two third of cases, the
      control of the epistaxis was obtained. In the other third, it was necessary to
      associate arteriography to a ligature of the ethmoidal arteries. As part of a
      preventive treatment of epistaxis we prefer, presently, to inject in situ a
      fibrin glue, which can be reviewed at the demand. These injections bring only
      exceptionally complications. The quality and duration of remission is judged
      satisfactory by the patients in 80% of the cases. Although no physio-pathological
      explanation can be brought, the intramuscular injections of fibrin glue could
      increase the duration of remission, which in this way, could diminish the
      frequency of injections in situ.

PMID- 9183909
TI  - [Dacryocystorhinostomy using Nd YAG laser by the intracanicular approach].
AB  - Endocanalicular dacryocystorhinostomy is a recent surgical procedure for stenosis
      of the naso-lacrymal duct, thanks to a laser filter fitted into the heart of 800
      mu diameter metallic pin constituting a rigid armed laser probe. We create a
      lacrymo-nasal orifice from inside the lacrymal bag towards the nose, using the
      laser fiber. The Nd YAG used is the solid state mobilisable Ophtalas sp 32 giving
      out infrareds at 1064 nm or green at 532 nm. The indications are the stenosis of
      the naso-lacrymal duct, the failed classical dacryocystorhinostomy, the
      conjunctivodacryocystorhinostomy and the stenosis of the common canaliculus. This
      surgical procedure compared to the classical surgical technics appears to the
      very promising due to its simplicity, innocuousness, time saving. Our results,
      still inferior to the classical technique for all indications (success rate: 70%)
      are very good for the idiopathic stenosis of the naso-lacrymal duct (success
      rate: 87.5%).

PMID- 9183910
TI  - [Acute cervical necrotizing fasciitis of pharyngeal origin: possible role of
      steroidal and non-steroidal anti-inflammatory agents. Apropos of 5 cases].
AB  - Within 20 cases of cervical acute necrotizing fasciitis treated in the intensive
      care unit and hyperbaric oxygen therapy department between 1986 and 1995, the
      authors report five cases of pharyngeal origin. 4 have been initially treated
      with anti-inflammatory drugs: non steroidal (1 case), steroidal (2 cases), non
      steroidal and steroidal (1 case). The five patients have been operated. They
      needed at least 30 days of endotracheal intubation and hyperbaric oxygen therapy.
      No death outcome but a important morbidity is reported. The immunosuppressive
      features of the two type of anti inflammatory drugs are exposed. Different
      publications suggesting the possible association between non steroidal anti
      inflammatory drugs and non cervical necrotizing fasciitis are reported. It is not
      possible to prove a direct link because of the number of our cases, because of
      the wide number of pharyngitis treated in the area, and because the absence of
      precise data about the use of anti inflammatory drugs in the initial treatment of
      this pharyngitis. Existence of other type of antalgic and non immunosuppressive
      drugs make the use of anti inflammatory drugs not justify.

PMID- 9183911
TI  - [Hemangiopericytoma of the infratemporal fossa of nasopharyngeal manifestation.
      Value of the cervico-transoral approach].
AB  - Authors present one case of hemangiopericytoma of the infra-temporal fossa and
      the lateral wall of the nasopharynx. They describe the characteristics of this
      rare, recurrent and sometime malignant vascular tumor. The selected therapy is an
      aggressive and wide exeresis. The antero-inferior approach via the cervico-trans
      oral route would seem to be of particular interest, offering good exposure of the
      anatomical features of the region avoiding the parotid bed ans dissection of the
      facial nerve.

PMID- 9183913
TI  - [Submental myocutaneous island flaps: anatomical study and prospective use].
AB  - The authors describe a myocutaneous cervical island flap based on the submental
      vessels. The anatomy based on 12 fresh cadaver dissection is outlined the
      submental arteries were injected with methylene blue, and the flap design and
      technique were studied. The flap has a long, reliable pedicle and cutaneous
      dimension measured 10 x 5 cm. The flap has an excellent skin color match and wide
      are of rotation and can extend to the whole homolateral face, the whole oral
      cavity, the whole homolateral oropharyngeal. The donor site scare dissimulated
      under the mandible is perfectly acceptable.

PMID- 9183912
TI  - [Cavernous hemangioma of the geniculate ganglion. Value of otoneurosurgical
      collaboration].
AB  - A patient with a progressive peripheral facial paralyses should be considered to
      have a tumor involved the facial nerve until proved otherwise. Haemangiomas of
      the temporal bone are uncommon and the present study discusses pathology,
      clinical presentation and therapeutic management of a tumor located at the
      geniculate ganglion. Complete surgical removal by the middle fossa approach is
      the treatment of choice with adequate margins and preservation of adjacent
      structures when it is oncologically possible. The surgeon must be familiar with
      all aspects of facial nerve repair.

PMID- 9183914
TI  - [Products of acoustic distortion in the examination of deafness in an infant].
AB  - Distortion-product otoacoustic emissions (DPOAEs) are otoacoustic emissions
      evoked by two pure tones. The greatest advantage of DPOAEs is their frequency
      specificity with respect to the eliciting bitonal stimuli. The purpose of this
      study was to compare DPOAEs in two populations. This paper reports input/output
      DPOAEs functions and DPOAE-audiograms for audiometric frequencies of f2 between
      696 and 6006 Hz in a normal neonate population and in an adult control group.
      Fifteen healthy fullterm newborns (29 ears) and 8 normal-hearing adults (16 ears)
      participated as subjects. Results at medium frequencies indicate that the maximum
      amplitudes of the DPOAEs were generated by neonates, the detection threshold was
      better and the dynamic range was greater than in adults, making them potentially
      valid for studying cochlear functioning in infants.

PMID- 9183915
TI  - [Multifrequency impedance audiometry and study of occupational deafness:
      "Teflag", a new test].
AB  - The mechanical acoustic theory compares the annular ligament of the stapes to an
      elastic plot; plot # 2. The coupled stapedial muscle and annular ligament partly
      ensure the dampening of acoustic impulses (low frequencies in particular) and
      helped by the stapes footplate, their transmission, by hydraulic pressure to the
      liquids of the cochlea. This muscle ligament couple represents the true impedance
      adaptor for the middle ear region. So as to study plot # 2 we have set up a test,
      called Teflag, using the otoadmittancemetre produced by Grason Stadler. This
      apparatus enables us to measure the functional state of the ligament (by the
      study of susceptance, representing the inverse of the reactive forces linked to
      the inertial mass of the system and to its compliance; in fact that of the
      ligament. We can also measure the level of the resistive intra-cochlear forces
      and those of the annular ligament (the study of conductance). Our study compares
      25 normal hearing patients and 64 ears with professional deafness. The Teflag
      gives us an evaluation of the functional state of the annular ligament, from
      morphological abnormalities of susceptance. Age induced hearing loss differs from
      professional deafness. A classification into 5 stages has been established
      following evaluation of functional annular ligament pathology. There is no
      hearing without oscillation (of a molecular order) of this ligament, which
      clearly seems to be the key point of the receptor organ, and ensures the
      detection of sound.

PMID- 9183916
TI  - Surgery under oto-endoscopic control.

PMID- 9183917
TI  - [Importance of meta-analysis in cardiology].

PMID- 9183918
TI  - [Effect models and meta-analysis].
AB  - The effect models are defined as the simple or complex relation that the risk in
      the treatment group follows when the risk in the control group varies. The
      standard statistical methods of meta-analysis are based on simple effect models.
      The use of these methods could induce inaccurate or erroneous results in more
      complex situations. In this case, it is necessary to adopt a more appropriate
      effect model, such as the linear effect model. The properties of this kind of
      model allow the possibility that a treatment can be beneficial and harmful at the
      same time, in function of the risk without treatment. From this observation, it
      is advisable to be careful with the use of simple effect models in meta-analysis
      which can submerge interesting information in the synthesis.

PMID- 9183919
TI  - [Role of meta-analysis in the definition of target population in therapy].
AB  - The efficacy of a drug is a quantitative concept rather than a qualitative one.
      This quantity is expressed by several efficacy indices. None of them meet all the
      requirements. However, that of absolute benefit is especially suitable for the
      patients because it tells them the exact gain they can expect from taking the
      treatment. The absolute benefit varies according to patients' profiles because it
      interacts with some components of these profiles. In theory, such interactions
      can be used to predict the size of the absolute benefit for each patient, as well
      to describe better than with the current tools the therapy target population. We
      explain why meta-analysis and effect models are means of improving the prediction
      of the size of the effect and the definition of the therapy target population.

PMID- 9183920
TI  - [Critical analysis of individual data in meta-analysis. Apropos of an experience
      in the domain of drug treatment in arterial hypertension].
AB  - Reliable syntheses are more and more needed by physicians. In the therapeutic
      field, this need is illustrated by the growing number of syntheses using meta
      analysis tools. Some of these syntheses are based on individual patient data, and
      this offers three kinds of advantages: the favourable consequences of a
      collaborative approach, the enhancement of data reliability, and a more complete
      extraction of useful information thanks to wider analysis potential. Most often,
      achieving the first two advantages does not require the individual patient data
      to be available, and a wider analysis potential seems to be the major rationale
      of such an approach. For instance, the assessment of the variation of treatment
      effect with along time is more accurate, but may also raise doubts about the
      validity of some hypotheses, for example, those underlying classical analysis
      techniques, or at the basis of even acknowledged pathophysiological theory.
      Ultimately, the concepts of identifying responders (here defined in terms of
      quantity or quality of life) and identifying the therapy target population are
      concretely applied in a way that will affect classical medical practice.
      Tomorrow, drugs will not be prescribed to a hypertensive individual because of
      the blood pressure level, but considering the size of the predicted therapeutic
      benefit.

PMID- 9183922
TI  - [Heparins and curative treatment of venous thromboembolic disease: meta
      analysis].
AB  - Heparin treatment of venous thromboembolic disease has been validated since 1960.
      Nevertheless no study was sufficient to determine an optimal therapeutic schedule
      between sub-cutaneous (SC) unfractionated heparin (UFH), intravenous (IV) UFH and
      low molecular weight heparin (LMWH). One meta-analysis showed a significant risk
      reduction of recurrent thromboembolic events (OR = 0.58, CI 95 per cent [0.34
      0.99]) and a non-significant risk reduction of haemorrhagic events (OR = 0.78
      [0.40-1.52]) with UFH SC compared to UFH IV, but homogeneity testing was
      significant (p < 0.001). Some discrepancy was shown between the results of the
      three metaanalyses which compared LMWH to UFH according to the selection criteria
      of clinical trials used. With an exhaustive selection, LMWH involved a non
      significant risk reduction of recurrent thromboembolic events (OR = 0.66 [0.41
      1.07], p = 0.09), and a non-significant risk reduction of haemorrhagic events (OR
      = 0.65 [0.36-1.16], p = 0.15). So no definitive conclusion could be drawn but it
      seems that UFH can be recommended whatever the administration route or LMWH for
      deep vein thrombosis treatment.

PMID- 9183921
TI  - [Nifedipine and coronary insufficiency: reasons for controversy].
AB  - Meta-analyses of Furberg's original data (after correction of two minor errors)
      were performed using six different methods. Only three of them gave significant
      results at p < 0.05. The sensitivity analysis showed that taking into account
      some of the criticisms applied to the original meta-analysis did not change the
      results. When all the criticisms were considered together, the 95 per cent
      confidence interval of the odds ratio for mortality was [0.96; 1.31] instead of
      [1.06; 1.37] originally (p = 0.14 and p = 0.03 respectively), and the dose excess
      mortality relationship stressed by Furberg disappeared. When the selection of the
      studies to be entered in a meta-analysis is not straightforward, a sensitivity
      analysis should be performed.

PMID- 9183923
TI  - [Antiplatelet agents and cardiovascular prevention].
AB  - The main contributions of meta-analysis methodology to antiplatelet therapy in
      the field of cardiovascular prevention are presented with regard to the different
      sectors of the health system: help with therapeutic information, help in the
      planning of clinical trials for the pharmaceutical industry and help in decision
      making for Health Authorities. The results of meta-analysis of available data
      concerning aspirin in cardio-vascular prevention are discussed, in an attempt to
      define optimal daily dose and duration of aspirin treatment.

PMID- 9183924
TI  - [Evaluation of drug iatrogeny by medico-economic modelling techniques].
AB  - Decision-making methods can be extremely useful in managing the large amount of
      information available on the complex effects of medication over various time
      spans. Event trees help to formulate data and visualise the medical strategies
      with the highest performance in regard to clinical benefits, adverse side
      effects, cost and cost-benefit ratios. However when the quantity of phenomena
      becomes too diversified (i.e. multiplicity of events, long observation periods,
      changing variables, etc.) we can use one of the more sophisticated modelling
      techniques available with today's more powerful computers.

PMID- 9183925
TI  - [Mycobacterium avium complex infections: the point on the treatments].
AB  - Mycobacterium avium complex (MAC) infections are the most frequent opportunistic
      infections in AIDS. Since progress in antiretroviral drugs enables AIDS patients
      to survive longer, these infections involve an increasing number of sick people.
      Few controlled assays have evaluated the efficiency of several antibiotics. When
      used in monotherapy, clarithromycin (one gram twice a day) appeared as the most
      efficient drug while the effectiveness of azithromycin, clofazimine, rifampin and
      liposomal encapsulated gentamicin have not been truly proved. Due to its
      bacteriologic and clinical effects, the most interesting polytherapeutic scheme
      is the association of clarithromycin (1 g twice a day), ethambutol (15 mg per kg
      and per day) and rifabutin (600 mg per day).

PMID- 9183926
TI  - Gingival hyperplasia: a new side effect associated with trimethoprim
      sulfamethoxazole (TML-SMX) treatment in pulmonary nocardiosis.

PMID- 9183928
TI  - Galactorrhoea induced by a pharmacodynamic interaction between citalopram,
      alprazolam and tramadol: a case report.

PMID- 9183927
TI  - Observations of the interaction between tricyclic antidepressants and fluvoxamine
      in poor metabolizers of dextromethorphan and mephenytoin.

PMID- 9183929
TI  - [Recurrent liver involvement induced by alverine].

PMID- 9183930
TI  - [Acute depressive syndrome possibly due to nilutamide (Anandron) treatment].

PMID- 9183931
TI  - [Paradoxal insomnia induced by flunarizine].

PMID- 9183932
TI  - [Severe hyponatremia induced by moclobemide].

PMID- 9183933
TI  - [What is a virus?].
AB  - Viruses are simple biological particles, consisting of a genome, a protein capsid
      and, in the case of enveloped viruses, an external lipidic envelope. Owing to the
      presence of envelope, most enveloped viruses are fragile although some exceptions
      may be observed. Viruses behave as complete intracellular parasites. Their
      multiplication results from the replication and self-assembly of viral
      components, this process being directed by the viral genome after it has been
      released within an infected cell. Virus classification is now essentially based
      on molecular properties, concerning both the structure and replication strategy
      of viruses. In virus taxonomy, serial hierarchical levels are family, subfamily,
      genus and species. Within species, lower hierarchical levels are type, subtype,
      variant and strain. Knowledge of virus structure and classification is essential
      for considering the physiopathology, diagnosis and therapy of viral infections.

PMID- 9183934
TI  - [Viral replication].
AB  - The multiplication of viruses depends on the virus and the infected cell. Viruses
      seem to have evolved by several routes and no single pattern of replication has
      prevailed. The cells can be permissive with productive infection or not. The
      productive cycle of viruses infecting eukaryotic cells exhibit several common
      steps. The initiation of infection--attachment, penetration and uncoating--sets
      up the viral gene for its replication and expression. These steps need specific
      viral enzymes, because the pathway required for the multiplication of the virus
      is not known by the cell. The last steps are assembly, maturation of the
      structural proteins, and finally the egress of viruses from the infected cells.

PMID- 9183935
TI  - [Mechanisms of viral diseases and means of natural defense].
AB  - This article concentrates on the mechanisms by which viruses cause disease.
      Although the emphasis is on mechanisms rather than on a description of individual
      viral infections, selected viruses that best exemplify important or novel virus
      host interactions are singled out. Twenty years ago, some viruses have helped
      understanding cell differentiation, and at present molecular and cellular biology
      are necessary to explain in depth the mechanisms of viral illnesses.
      Understanding and control of viral diseases are not mutually exclusive but rather
      simultaneous processes with multidisciplinary approaches. Like some bacterial
      toxins, virus may be deleterious without infecting cells. To use the cell
      machinery efficiently, viruses must be able to escape the immune system.

PMID- 9183936
TI  - [Drugs active against herpesviruses].
AB  - Drugs active against herpesvirus are undergoing rapid development. Acyclovir is
      the antiviral drug of choice for treatment of herpes simplex virus (HSV)
      infections and the varicella and zona virus (VZV) because of its efficacy and
      lack of toxicity. Valaciclovir, precursor of acyclovir, allows reducing the daily
      intake to 2 doses for HSV infections and to 3 doses for VZV. For cytomegalovirus
      infections and HSV that are resistant to acyclovir in immunodepressed patients,
      ganciclovir and foscarnet are available and effective but can involve
      respectively haematologic and renal toxicity. Penciclovir, the active form of
      famciclovir, is a new antiviral drug indicated in the treatment of zona.

PMID- 9183937
TI  - [Drugs active against retroviruses].
AB  - Major advances in understanding the pathogenesis and treatment of human
      immunodeficiency virus (HIV) infection have been made recently. The reverse
      transcriptase and protease enzymes of HIV are currently the targets of
      antiretroviral therapy. Nucleoside analogues were the first class of
      antiretroviral drugs which demonstrated antiviral activity in treating patients.
      More recently protease inhibitors have provided new approaches in the treatment
      of HIV infection, with encouraging trial results in patients receiving combined
      therapy. This review presents their mechanisms of activity and patterns of
      resistance. Apart from these main drug groups many new compounds are under
      development.

PMID- 9183938
TI  - [Drugs active against hepatitis viruses].
AB  - Chronic viral hepatitides B, C and D and their long-term consequences--cirrhosis,
      primary hepatic cancer--have become a worrisome public health problem. Although
      results with interferon alpha have been encouraging they remain modest. Many
      uncertainties remain concerning optimal dosage, length of treatment, the interest
      of repeated treatment and what might be gained by association with other
      antiviral molecules, particularly nucleoside analogues. These uncertainties
      explain the abundance of clinical studies, sometimes yielding contradictory
      results. Thus, further multicentric trials are required, and further fundamental
      research which may lead to new classes of molecules needs to be supported.

PMID- 9183939
TI  - [Drugs active against respiratory viruses].
AB  - Few molecules are active against respiratory viruses. In upper respiratory tract
      infections, which are frequent and fortunately not severe, their deficiency is
      not a problem. However some molecules are able to block in vitro the interaction
      between a rhinovirus and its receptor: anti-receptor antibodies, soluble ICAM-1,
      capsid-binding agents. The lower respiratory tract infections (bronchiolitis,
      pneumonia...), mainly due to respiratory syncytial virus and influenza viruses
      are potentially more severe, and 2 groups of compounds are or have been used in
      these infections: amantadine and ribavirin. Ribavirin is effective in respiratory
      infections due to respiratory syncytial, influenza and parainfluenza viruses, and
      on many other viruses. Its toxicity needs to administrate it as an aerosol, and
      in France, ribavirin is used as compassional treatment in severe forms of
      bronchiolitis or pneumonia due to respiratory syncytial virus, and in high-risk
      children. Anti-parkinsonian drugs, related to amantadine (Mantadix, Roflual) are
      no longer on sale. Therefore there is no active molecule yet available against
      these viruses.

PMID- 9183940
TI  - [The future of antiviral drugs].
AB  - Despite much recent progress, antiviral chemotherapy has still to meet some major
      challenges: residual cytotoxicity of much antiviral drugs; emergence of viral
      strains resisting to the most specific antiviral drugs; inability of the most
      active antiviral drugs to suppress latent viral infections. Several approaches
      using gene therapy (e.g. hybridons, ribozymes, or dominant negative mutants)
      might theoretically provide efficient solutions against viral latency.

PMID- 9183941
TI  - [Myogenous syndrome. Diagnostic orientation].

PMID- 9183942
TI  - [Normal and pathological cicatrization. Physiopathology and anatomopathology].

PMID- 9183943
TI  - [Prematurity and hypotrophy at birth. Epidemiology, causes and prevention].

PMID- 9183944
TI  - [Obesity. Epidemiology, diagnosis and complications].

PMID- 9183945
TI  - [Urinary incontinence in adults. Diagnostic orientation].

PMID- 9183946
TI  - [Morbidity and mortality from acute drug poisoning in France].
AB  - In France, drugs are responsible for 40% of accidental poisonings in children and
      80% of voluntary poisonings in adults. The annual incidence voluntary drug
      poisonings is evaluated at 4 per 1000 individuals. Their morbidity and severity
      have decreased considerably during the past 25 years. A toxic symptom is found in
      less of 50% of the cases. The fraction of patients hospitalized for drug
      poisoning mortality is low (0.1%), principally in adult voluntary poisoning. The
      benzodiazepins are responsible for 80% of the poisonings but they are much less
      toxic than barbiturates. The development of preventive actions and pharmacologic
      and toxicologic vigilance allowed to limit use of the most dangerous psychotropic
      drugs or to remove them from the market.

PMID- 9183947
TI  - [Determination of drugs for the diagnosis and the surveillance of acute
      poisoning].
AB  - Acute drug poisonings are the first cause of hospital admission among in
      individuals less than 30 years of age in developed countries. In order to face
      this problem, an analytic process, including two steps, is proposed; first, a
      qualitative step leads quite quickly to a medical diagnosis; second, a
      quantitative step, in close collaboration with the clinician, allows a well
      adapted reanimation. The result is that the patient receive a quicker and more
      efficient treatment. Both the analyst and the clinician must know the limits and
      the requirements of such techniques.

PMID- 9183948
TI  - [New acute poisoning syndromes of drug origin].
AB  - The slow but constant modifications of the pharmacopeia and prescribing habits
      are at the origin of changes in the causes of intoxications by medications, which
      are reflected in the syndromes observed in daily practice. New syndromes have
      appeared: serotoninergic syndrome, adrenergic syndromes, toxic malignant
      hyperthermia, opioid toxic syndrome, intoxication by drugs with membrane
      stabilizing effect. Recognizing these syndromes is not only useful to determine
      the possible causes of on intoxication, but also to direct appropriate, specific
      therapeutic interventions.

PMID- 9183949
TI  - [Acute poisoning by new psychotropic drugs].
AB  - New tricyclic antidepressants such as amineptine and tianeptine have mild toxic
      effects while amoxapine is very toxic. Poisoning with new selective serotonin
      reuptake inhibitor antidepressants or monoamine-oxidase inhibitors type A
      (toloxatone, moclobemide) is usually not severe, but life-threatening serotonin
      syndromes may appear in case of drug combination with antidepressants. Loxapine
      and clozapine poisoning may lead to death while risperidone intoxication has
      usually a rather benign course. Substituted benzamide neuroleptics (amisulpride,
      sultopride) may induce seizures, QT prolongation and torsades de pointes. New
      hypnotics such as zolpidem and zopiclone have a mild toxicity similar to that of
      benzodiazepines, but coma and respiratory depression are observed if other drugs
      or ethanol are ingested or in case of chronic hepatic or respiratory
      insufficiency.

PMID- 9183950
TI  - [Acute paracetamol and aspirin poisoning].
AB  - Liver injury is the main feature of paracetamol poisoning. Early administration
      of N-acetylcysteine is an effective antidotal treatment. There are also effective
      treatments for salicylate poisoning and severe cases are always due to delayed
      diagnosis. Salicylate poisoning should be systematically suspected when several
      of the following features are observed in a poisoned patient: tinnitus, deafness,
      hyperventilation, respiratory alkalosis, metabolic acidosis. Diagnosis is readily
      confirmed by measuring plasma salicylate concentration.

PMID- 9183951
TI  - [Acute poisoning by beta-blockers and by calcium inhibitors].
AB  - beta-blockers and calcium-channel inhibitors are frequently used for self
      poisoning. Propranolol and verapamil, the leading drugs in each pharmacological
      class, are the most toxic. They interfere with intracellular calcium
      concentration in muscles. Circulatory insufficiency may be due to vasodilatation,
      myocardial depression or severe bradycardia. If one respects a specific sequence
      for administration, the usual antidotes (glucagon, calcium salts, isoprenaline,
      epinephrine) are usually efficient. One must not underestimate the risk of
      worsening of an intoxication that is seen at the early stage, that occur in an
      old person or in a patient with heart disease, or that depress ventilation.
      Hence, it is important to monitor and treat these intoxications in an intensive
      care unit.

PMID- 9183952
TI  - [Acute poisoning by class I anti-arrhythmia agents and by chloroquine].
AB  - Poisonings with class I antiarrhythmic drugs and chloroquine are characterized by
      their severity, related to their membrane-stabilizing effect. Because of the
      rapid onset of severe cardiovascular disturbances with circulatory arrest,
      cardiogenic shock, conduction abnormalities, ventricular dysrhythmia, rapid
      hospitalisation in an intensive care unit is mandatory with continuous monitoring
      of electrocardiogram, blood pressure and biological variables. Treatment includes
      mechanical ventilation, inotropic agents, especially epinephrine, hypertonic
      sodium salts, and diazepam in case of chloroquine poisoning.

PMID- 9183953
TI  - [Immunotoxicotherapy].
AB  - Immunotoxicotherapy has been used against animal venoms for almost a century. The
      last several years have brought major innovations in its safety and efficacy, the
      processes of fragmentation permitting a greater volume of distribution,
      diminished risk of sensitization and renal elimination. This progress is clearly
      illustrated in the case of digitalis and colchicine. Hope exists for tricyclic
      antidepressants and cocaine. The efficacy of immunotoxicotherapy does not
      eliminate the necessity of aggressive symptomatic therapy in the course of life
      threatening intoxications. Untoward effects appear rare and minor, mainly due to
      the heterogeneity of active binding sites and to immunogenicity (with risks of
      hypersensitivity and serum sickness). The elevated cost of immunotoxicotherapy
      and its restriction to drugs toxic at low doses (on the order of a few mg) limit
      its application at present.

PMID- 9183954
TI  - [Cellular and extracellular dehydration and hyperhydration. Etiology,
      physiopathology, diagnosis, treatment].

PMID- 9183955
TI  - [Obliterative arteriopathy of the aorta and lower limbs of atheromatous origin.
      Diagnosis, course, complications, treatment].

PMID- 9183956
TI  - [Chronic hepatitis B and C. Epidemiology, diagnosis, course, prevention].

PMID- 9183957
TI  - [Sudden-onset deafness. Diagnostic orientation].

PMID- 9183958
TI  - [Peripheral neuropathies. Etiology, diagnosis].

PMID- 9183959
TI  - [Epidemiology and etiology of malignant gastric tumors].
AB  - Stomach cancer remains a common type of cancer, though its incidence has been
      halved in the last forty years. It is unevenly distributed throughout the world.
      In France, it holds fifth place among cancers and there are 8700 new cases each
      year. Helicobacter pylori infection, a high salt intake as well as an inadequate
      diet take part in the first stages of carcinogenesis. Later on, nitrates and
      nitrites, polycyclic hydrocarbons, alcohol, tobacco and bilc acids are
      incriminated. The protective role of vegetables and fruit has been well
      established. The protective role of vitamin C and beta-carotene is currently
      undergoing evaluation in subjects suffering from precancerous conditions such as
      dysplasia and incomplete intestinal metaplasia. The development of a vaccine
      against Helicobacter pylori induced infection also represents an important goal.

PMID- 9183960
TI  - [Diagnosis of gastric tumors].
AB  - Gastric adenocarcinomas are currently diagnosed at an advanced stage, related to
      non specific and late symptoms. Gastroscopy is the first examination to perform
      in case of recurrent epigastric pain, nausea, loss of weight, anorexia.
      Endoscopic diagnosis is usually easy in case of polypoid and ulcerative mass,
      sometimes more difficult in case of linitis plastica or tiny mucosa lesion.
      Biopsies are mandatory and allow to type cancer in intestinal and diffuse forms.
      Imaging techniques by X-ray series, sonography, scanner or echo endoscopy are
      useful to select patients for surgical procedure.

PMID- 9183961
TI  - [Contribution of imaging of gastric cancers].
AB  - Medical imaging techniques have gradually lost their place in the diagnosis of
      gastric neoplastic tumors since endoscopic ultrasonography appears. Today,
      classical esophageal gastric duodenum barium examination is only practiced in
      preoperative staging. Anyway, endoscopic ultrasonography and transabdominal
      sonography have a great part in the staging of locoregional and general
      extension, as well as in patients observation.

PMID- 9183962
TI  - [Gastric lymphoma].
AB  - The stomach is the most common site involved in primary gastrointestinal
      lymphoma. Gastric lymphoma originates from the mucosa-associated lymphoid tissue
      so called MALT. It comprises a group of distinctive clinicopathological entities
      which are important to take in account for clinical behavior. In recent years,
      new diagnostic tools and modern modes of treatment have improved their overall
      prognosis. One of the most exciting recent discoveries is the hypothesis that an
      infection by a bacterium. Helicobacter pylori has a decisive role in gastric
      lymphoma.

PMID- 9183963
TI  - [Surgical treatment of cancers of the stomach].
AB  - Gastric cancer remains a serious health problem 5 years survival remains low and
      early diagnosis anecdotical in France. Gastrectomy is the only curative treatment
      and the extent of surgery depends upon the tumor location. The extent of the node
      dissection is under discussion, Japanese surgeons recommend extensive dissection
      and publish better results in term of survival than Europeans groups. Two
      randomized prospectives trials comparing limited and extensive dissection have
      not shown any difference but an increased morbidity in the group with extensive
      dissection. Adjuvant treatments radiation or chemotherapy should be given
      therapeutic trials because they have not been proved as efficient.

PMID- 9183964
TI  - [Non-surgical treatment of cancers of the stomach].
AB  - In western countries, most gastric cancers are diagnosed at locally advanced
      stages. Surgery is the only curative treatment, but the risk of locoregional
      relapses and of distant metastases is very high. This is the rationale for
      adjuvant treatments. However, currently available data do not allow a definitive
      conclusion as to whether chemotherapy or radiation therapy are of value as
      adjuvant treatments for poor-prognosis gastric cancers. Further randomized
      clinical trials are still needed. By contrast, it is admitted that these
      treatments have a palliative role in the management of patients with metastases.

PMID- 9183965
TI  - [Gastric carcinoid tumors].
AB  - Gastric carcinoid tumors are divided up into three groups of various presentation
      and prognosis. Carcinoids tumors on fundic atrophic gastritis with achlorhydria
      resistant to pentagastrine stimulation, the most numerous, and those observed in
      patients with Zollinger-Ellison syndrome, are fundic, readily small and numerous,
      of slow evolution with rare metastasis and without carcinoid syndrome. They are
      associated with an hypergastrinemia of antral or tumoral origin, responsible for
      a diffuse endocrin hyperplasia upon which they rest. The other carcinoid tumors,
      called sporadic, are usually unique and more voluminous, much more aggressive.
      They are accompanied by a carcinoid syndrome in one third of the cases. They
      occur without any hypergastrinemia and rest on a entirely normal gastric mucosa.
      The diagnosis of gastric carcinoid tumor imperatively requires an assessment
      intended to classify the tumors and to set up therapeutic indications.

PMID- 9183967
TI  - [Prolonged activated partial thromboplastic time, Quick's time, bleeding time.
      Diagnostic orientation].

PMID- 9183966
TI  - [Benign tumors of the stomach].
AB  - The term "benign gastric tumours" comprises three distinct entities: submucosal
      tumours, polyps and carcinoid tumours. Submucosal tumours are rare and most often
      conjunctive (leiomyoma, schwannoma, lipoma, etc.), but may also be heterotopic or
      congenital. Because of their subepithelial location, samples taken during
      endoscopic examination are rarely contributory. Endoscopic ultrasonography is the
      examination of reference for characterisation of these tumours. Polyps of
      epithelial origin, are common, most often small and without degenerative
      potential. They can be histologically diagnosed during endoscopic
      ultrasonography. Carcinoid tumours, which are very rare, are discussed elsewhere
      in this issue.

PMID- 9183968
TI  - [Erythema. Diagnostic orientation].

PMID- 9183969
TI  - [Drugs and the eye. Secondary ocular effects of local and general corticoids,
      synthetic antimalarials and parasympatholytics; extra-ocular secondary effects of
      beta-blocker eyedrops and sympathomimetic eyedrops].

PMID- 9183970
TI  - [Pyramidal syndrome. Diagnostic orientation].

PMID- 9183971
TI  - [Acute hypertensive crisis. Diagnosis and management in emergency situation].

PMID- 9183972
TI  - [Osteoporosis. Epidemiology, etiology, diagnosis, prevention].

PMID- 9183973
TI  - [The self-perception of their professional role of the primary care physicians of
      Estonia and Finland].
AB  - OBJECTIVE: To find out how experienced primary care physicians working in
      different societies see themselves as doctors. DESIGN: A cross-sectional study.
      SETTING: Primary health care in Estonia and Finland. PARTICIPANTS: Estonian
      district doctors (n = 110) and Finnish specialists of general practice (n = 211).
      METHODS: In a postal questionnaire the respondents were asked to evaluate how
      well 18 different expressions described them as doctors on a 5-step scale from "1
      = very poorly" to "5 = very well". RESULTS: Four of the five expressions that
      were thought most accurate and telling--"Listener", "Vocational doctor",
      "Helper", and "Family physician"--were the same in Estonia and Finland.
      CONCLUSIONS: Even though there are differences in health care systems, the self
      images of primary care doctors in both countries were more or less consistent
      with the international definitions of the general practitioner's job and role.

PMID- 9183974
TI  - Rotated object identification with and without orientation cues.
AB  - The time to name two-dimensional line drawings of objects increases linearly for
      object rotations between 0 degrees and 120 degrees from the upright. Several
      theories attribute these effects of orientation to finding the top or the top
      bottom axis of objects. By this account, prior knowledge of the location of the
      top or the top-bottom axis of objects should diminish effects of object
      orientation when they are named. When this hypothesis was tested by cuing the top
      or the top-bottom axis, no reduction in the effects of orientation on object
      naming was found. This result is inconsistent with effects of orientation on
      object naming being due to finding the top or the top-bottom axis. Instead, the
      top may be found prior to rotational normalization of the object image.

PMID- 9183975
TI  - Word frequency effects and eye movements during two readings of a text.
AB  - The present study examined the influence of word frequency on rereading
      performance. Subjects read short passages, each twice in succession, while their
      eye movements were monitored. During first presentations, each passage contained
      a target word of low or high frequency; during second presentations, the targets
      were either repeated or replaced by synonyms. In general, during the second
      readings readers made shorter duration fixations, fewer fixations, and longer
      saccades. When fixation times on the target words were examined, results showed
      that fixation durations were shorter for high frequency words during both
      readings and that the decrease in fixation duration was similar in magnitude for
      low and high frequency words. This suggests that word frequency and repetition
      independently influenced reading time. In addition, replacing a target with a
      synonym did not increase processing time for the replacement word. This suggests
      that conceptual repetition was sufficient for obtaining repetition effects when
      reading text.

PMID- 9183976
TI  - Perceiving the tonal ending of tune excerpts: the roles of pre-existing
      representation and musical expertise.
AB  - In this study, sensitivity to tonal relations was assessed by using real melodies
      instead of traditional scales or chords. Two groups of listeners-one trained, one
      untrained-rated the goodness of fit of each of the 12 tones of the chromatic
      scale as the final note of familiar and unfamiliar tune excerpts. The unfamiliar
      excerpts were the mirror forms in pitch and time of the familiar tunes. The
      results showed that musicians and nonmusicians exhibited responses that were
      governed by tonal relations with both familiar and unfamiliar tunes. These
      findings were corroborated by multiple-regression analysis, which revealed that
      the pattern of ratings reflected knowledge of the musical structure, beyond the
      contribution of surface features such as note frequency or pitch proximity
      between the two last tones.

PMID- 9183977
TI  - Orthographic effects on phoneme monitoring.
AB  - A widely used task in the research on spoken word recognition is phoneme
      monitoring, in which subjects have to detect phonemes in spoken words. It is
      generally assumed that this task is performed using phonetic or phonological
      representations of words only. To test whether an orthographic representation of
      the words is employed as well, an experiment was conducted in which Dutch
      subjects monitored for phonemes with either a primary or secondary spelling in
      phonologically matched spoken words and nonwords. Phoneme monitoring times were
      slower when the phoneme had a secondary spelling than when it had a primary
      spelling. The effect was greater after than before the uniqueness point of the
      word, and monitoring times were faster for words than for nonwords. These
      findings indicate that an orthographic representation of words is engaged in
      phoneme monitoring.

PMID- 9183978
TI  - Unattended words need to be primed to be recognized.
AB  - The categorical relation between a target word and a flanking, to-be-ignored,
      nontarget word can influence target response. Although usually taken as evidence
      of a full and automatic analysis of stimuli whether or not they have been
      attended, this flanker effect may only point to the failure of focused attention
      when nontarget stimuli have been primed and made task-relevant. The present study
      examined the role of priming in the flanker task. In one condition, schematic and
      semantic priming of nontargets was potentiated by having subjects categorize the
      target as an instance of a living or nonliving thing. In a second condition,
      priming was minimized by requiring only a shallow analysis of the target for a
      response; subjects searched the target for the presence of the letter R. A
      flanker effect was found only in the categorization condition, and then only when
      the target was the name of an animal. There was no evidence that unattended
      nontargets had been fully and automatically encoded to a semantic level.

PMID- 9183979
TI  - Does irrelevant stimulus location affect response selection?
AB  - Reaction time (RT) is shorter when the irrelevant location of the stimulus
      corresponds to the relevant location of the response: When a subject is to
      perform a left or right keypress according to the colour of a stimulus delivered
      either to the left or to the right of a fixation, RT is typically shorter when
      the location of the stimulus corresponds to the location of the response (e.g.,
      left stimulus/left response) than when it does not (e.g., left stimulus/right
      response). Umilta and Nicoletti (1990) have suggested that this effect, known as
      the ?Simon effect' in the literature, occurred at the response selection stage, a
      stage whose duration depends on the effectors used to perform the task. In the
      present study, this effect and that of the finger response repertoire (within-
      versus between-hand composition) were found to be additive, which does not
      support the response selection hypothesis of the Simon effect.

PMID- 9183981
TI  - Lateralization of high frequency sounds as a function of interaural amplitude
      disparity.
AB  - Twenty-five subjects made graphic ratings of the perceived lateral position
      within the head of sounds presented through headphones. The stimuli were high
      frequency, pure tones and amplitude modulated sounds. For the amplitude modulated
      sounds, a 200 HZ modulation frequency was combined with carrier frequencies of
      2200 HZ, 3200 HZ, 4200 HZ, and 5200 HZ, which were also the pure tone
      frequencies. Interaural level differences in the signals ranged from zero to 12
      dB. The rate of lateralization was defined as the slope of the linear trend
      relating laterality ratings to interaural level differences. The rate of
      lateralization was found to be a decreasing function of frequency. The laterality
      ratings of amplitude modulated signals were nearly identical to those for pure
      tones. This result suggests that, for high frequency signals, conflicting
      temporal information that a source is centered is suppressed in favor of
      information from level differences that the source is off-center.

PMID- 9183980
TI  - Search for letter identity and location by disabled readers.
AB  - Reading-disabled boys, reading- and age-matched controls, and adults searched
      letter arrays for the identity or location of a probe letter. Response time (RT)
      and accuracy were examined as a function of the temporal relation between probe
      and array letters (probe first, simultaneous, array first), and array size (1-5
      letters). Although disabled readers closely resembled age controls in RT, their
      accuracy differed significantly when large letter arrays were tested. In the
      letter identification task, this was only evident when the array letters preceded
      the probe; in the letter location task, it occurred in all three probe
      conditions. Correlational analyses showed that all subjects were influenced by
      the visual, but not the phonological, similarity between letters. Thus, a reading
      related impairment is evident in both letter identification and letter location
      processes, even when the phonological coding of letters has been minimized.

PMID- 9183982
TI  - Age and handedness: patterns of change in the population and sex differences
      become visible with increased statistical power.
AB  - In a sample of 12,030 subjects, ranging in age from 8 to 99 years, significant
      decreases in both mixed and consistent left-handedness were found as age
      increased. There were also significant sex differences, with males more likely to
      be left- or mixed-handed. These age and sex differences were reported as non
      significant in Porac's (1993) smaller sample of 654. Methodological issues
      associated with asserting the null hypothesis in handedness studies when
      statistical power is low are also discussed.

PMID- 9183983
TI  - Pupillometric assessment of compensatory effort in a memory search task under
      physical and pharmacologically-induced suboptimal states.
AB  - Extensive research has shown that the phasic pupil size (peak level on each
      trial) is a sensitive measure of the degree of mental effort demanded by a task.
      In the present study, the validity of the pupil response as an index of mental
      effort in suboptimal conditions was investigated. Thirteen males (19-29 years)
      performed a memory and display-search task in a practice session, followed in
      random order by an oxazepam session, a placebo session, a physical exercise
      session, and a control session. After both oxazepam and physical exercise,
      decision times increased, but pupil response increased only after physical
      exercise. This result was explained by the possibility that under physical
      fatigue, compensatory effort was exerted, whereas under drug-induced fatigue,
      subjects seemed unable to compensate for the performance decrement. The pupil
      response appears to be a valuable tool for gaining more insight into different
      effects of suboptimal states.

PMID- 9183984
TI  - On the calibration of knowledge and perception.
AB  - This study examined confidence judgements (i.e., calibration, resolution, and
      over/underconfidence) and response times in an intellectual knowledge task and a
      perceptual task requiring location comparisons. At each of four levels of
      judgement difficulty (i.e., Easy, Hard, Impossible and Misleading/Illusory), very
      similar properties were evident in the two tasks. The results are inconsistent
      with theories that assume a fundamentally different basis for confidence in human
      knowledge and perception.

PMID- 9183985
TI  - Indirect learning of event sequences: the effects of divided attention and
      stimulus continuity.
AB  - In a serial reaction time (SRT) task, the learning curve is sleeper when the
      stimuli are presented in a repeating sequential manner rather than in random
      order (Nissen & Bullemer, 1987). This is true even when subjects report being
      unaware of the presence of the repeating sequence. The present study examines the
      nature of this learning under conditions designed to reduce attentional resources
      and to disrupt the continuity of stimuli. In the first three experiments,
      subjects were trained in the SRT task, with or without the addition of a
      secondary tone counting task, and with repeating or non-repeating sequences. The
      results suggest that some sequence learning occurred despite the presence of a
      secondary task. Experiment 4 examined the extent of sequence learning when the
      inter-stimulus interval was varied between trials. The overall results suggest
      that despite reduced attentional allocation and discontinuous stimulus
      presentation, some sequence learning occurs. This result supports other work
      suggesting a dissociation between learning when measured explicitly, and when
      assessed through performance indicators.

PMID- 9183986
TI  - Encoding operations and recognition memory for faces.
AB  - Two experiments examined the effects of encoding operations on forced-choice
      recognition memory for upright and inverted photographs of faces. In Experiment
      1, with distractors closely matched to targets, performance was better on upright
      than on inverted faces, but was unaffected by whether subjects judged faces for
      distinctive features, distinctive traits or distinctive expressions. In
      Experiment 2, where distractors were either absent or weakly matched to
      distractors, accuracy was again higher on upright than on inverted faces, and was
      similar for the three encoding operations on upright faces. In contrast, it was
      poorer for distinctive expression judgments than for distinctive feature or for
      distinctive trait judgments on inverted faces. These results support Winograd's
      (1981) claim that distinctive feature and distinctive trait judgments both lead
      to the isolation of distinctive features. However, it was argued that distinctive
      expression judgments led to configural processing that was disrupted by
      inversion.

PMID- 9183987
TI  - Letter localization, not discrimination, is constrained by attention.
AB  - Shaw (1984; Shaw, Mulligan & Stone, 1983) measured the probability of detecting a
      target letter in displays containing different numbers of items. The set size
      effect was significantly larger than the effect predicted by unlimited-capacity
      models of visual processing, and Shaw concluded that attention constrains the
      discrimination of complex, but not simple, patterns. We re-examined the role of
      attention in letter discrimination by measuring the effect of set size on the
      contrast needed to identify a target embedded among distractors. The results of 5
      experiments show that set size effects are small for letter discrimination, but
      large for letter localization. The findings suggest that the large set size
      effect reported by Shaw (1984) was a result of asking subjects to localize the
      target. In addition, the results are consistent with the hypothesis that limited
      processing capacity constrains the perceptual processes involved in letter
      localization, but not discrimination.

PMID- 9183988
TI  - Patterns of handedness in modern Japanese: a cohort effect shown by re
      administration of the H.N. Handedness Inventory after 20 years.
AB  - The H.N. Handedness Inventory, originally administered to a sample of 1199
      Japanese students in 1973, was administered to a new sample of 1700 Japanese
      students 20 years later. It was found that the population of left-handed and
      ambidextrous females had increased. The incidence of inverted left-hand writers
      was very small. Comparison of the two sets of data demonstrates the effects of
      non-biological factors upon lateral preference.

PMID- 9183989
TI  - A strategic account of the cue-depreciation effect.
AB  - A word fragment is less likely to be completed if it is presented incrementally
      (R______P, R____R _ P, R_I__R_P, R_I__R O P) than if it is presented all at once
      (e.g., R_I__R O P). This phenomenon is known as the cue-depreciation effect. The
      present study examined the role of strategies in this phenomenon. The magnitude
      of the cue-depreciation effect was increased when subjects were asked to adopt a
      passive generation approach to word fragment completion. The current study
      investigated an extension of Bruner and Potter's (1964) early hypothesis
      generation account of the cue-depreciation effect. Findings demonstrated the
      influence of completion strategies for a general theory of fragment completion.

PMID- 9183990
TI  - Sex differences in visuo-spatial ability: task difficulty, speed-accuracy
      tradeoff, and other performance factors.
AB  - Males have consistently been found to perform better than females on a task that
      requires the subject to mentally rotate a figure. Recently, Goldstein. Haldane,
      and Mitchell (1990) suggested that performance factors are operative in
      explaining sex differences in spatial ability. However, Stumpf (1993) was unable
      to replicate all of Goldstein et al.'s (1990) findings and to generalize them to
      other measures of spatial ability. In this study, it was hypothesized (1) that
      females would take longer to respond and would get fewer correct items than males
      on a spatial rotation task, and (2) that only females would show a speed-accuracy
      tradeoff as the difficulty of the spatial task increased from the 90 degrees to
      180 degrees rotated conditions. The results confirmed each of these hypotheses.
      Furthermore, as Stumpf (1993) found, when ratio scores from the number of items
      correct to number attempted were computed for both males and females, differences
      in spatial ability were reduced, though still evident.

PMID- 9183991
TI  - Neutral location cues and cost/benefit analysis of visual attention shifts.
AB  - The effects of location cuing on target responses can be examined by comparing
      informative and neutral cuing conditions. In particular, the magnitudes of costs
      of invalid location cuing and of benefits of valid location cuing can be
      determined by comparing invalid and valid cue responses to location-nonspecific
      neutral cue responses. Cost/benefit analysis is based on the assumption that
      neutral baseline measures reflect a general warning effect about the impending
      target's onset but no other specific target information. The experiments we
      report were carried out to determine the appropriateness of two baseline measures
      for cost/benefit analyses of direct (nonsymbolic) location cuing effects. We
      found that a multiple-cue baseline attenuated the benefits of valid cuing, and
      that a background-flash baseline arbitrarily attenuated costs or benefits
      depending on flash intensity. It is proposed that a background flash is the more
      suitable neutral cue because it is target-location-nonspecific, but that its
      intensity should be adjusted to elicit a target-onset warning signal of the same
      magnitude as the location cues with which it will be compared.

PMID- 9183992
TI  - On knowing which way to trace: direction errors during visual curve tracing.
AB  - McCormick and Jolicoeur's (1991; 1994) zoom lens model of visual curve tracing
      proposes that curve tracing involves tracking a curve with a variable size local
      operator. Unspecified in their model is how the executive function guiding the
      processing field of this operator initially knows which direction to trace. An
      experiment was conducted to determine whether observers occasionally curve trace
      in the wrong direction. A typical curve tracing task involving the determination
      of whether two dots occur on the same line in a display consisting of two dots
      and two intertwining lines was used. Lengthening the curve segment at the
      beginning of a to-be-traced curve resulted in a slowing of response times only to
      dot locations close to the end of the to-be-traced line. Apparently, observers
      calculate curve tracing direction based on the spatial location of the second
      (i.e., target) dot, which can result in erroneously tracing in the wrong
      direction at dot locations farther along the line.

PMID- 9183993
TI  - Brain size matters: a reply to Peters.
AB  - Peters (1993) claimed that published research on brain size and IQ is flawed
      because it did not meet his list of "minimum conditions" that (a) subjects should
      be matched for height, weight and age, (b) analyses should be conducted
      separately within sex, (c) subjects should not vary in prenatal and nutritional
      history, (d) people with IQS appreciably below the population mean of 100 should
      not be studied, and (e) brain size measures should be done "blind". However,
      these "conditions" have either been met or are unnecessary and/or inappropriate.
      We show, contrary to Peters' claims, that (a) brain size is related to mental
      abilities, (b) brain size varies by sex and race, and (c) mental abilities vary
      by sex and race. Finally, we suggest that brain size constraints on behavioural
      complexity may be best understood from an evolutionary perspective.

PMID- 9183994
TI  - Molecular basis of Zellweger syndrome, beta-ketothiolase deficiency and
      mucopolysaccharidoses.
AB  - 1. A human peroxisome assembly factor-1 (PAF-1) complementary DNA has been cloned
      that restores the morphological and biochemical abnormalities (including
      defective peroxisome assembly) in fibroblasts from a patient with group F
      Zellweger syndrome. The cause of the syndrome in this patient was a point
      mutation that resulted in the premature termination of PAF-1. The homozygous
      patient apparently inherited the mutation from her parents, each of whom was
      heterozygous for that mutation. Furthermore, we cloned and characterized the rat
      and human cDNAs for peroxisome-assembly factor-2 (PAF-2), which restores
      peroxisomes of the complementary group C Zellweger cells, by functional
      complementation, and identified two pathogenic mutations in the PAF-2 gene in two
      patients. 2. Seventeen mutations have been identified in 13 mitochondrial
      acetoacetyl-CoA thiolase-deficient patients. 3. We purified N-acetylgalactosamine
      6-sulfate (GalNAc6S) sulfatase and cloned the full-length cDNA of human N
      acetylgalactosamine-6-sulfate sulfatase (GALNS). The gene encoding GalNAc6S
      sulfatase has been localized by fluorescence in situ hybridization to chromosome
      16q24, and the entire genomic gene structure has been characterized. About 40
      different GALNS gene mutations have been identified in the patients with
      mucopolysaccharidosis IV A.

PMID- 9183995
TI  - Nonketotic hyperglycinemia: biochemical, molecular, and neurological aspects.
AB  - Nonketotic hyperglycinemia (NKH) is a metabolic disorder with autosomal recessive
      inheritance, causing severe, frequently lethal, neurological symptoms in the
      neonatal period. The metabolic lesion of NKH is in the glycine cleavage system
      (GCS), a complex enzyme system with four enzyme components; P-, T-, H-, and L
      protein. The enzymatic analysis revealed that 86% of the patients with NKH are
      deficient of P-protein activity. The cDNA clones encoding all four components
      were isolated and their primary structures were determined. Several mutations
      have been identified in P- and T-protein genes: One missense mutation, S564I, in
      P-protein gene accounts for 70% of the mutant alleles in Finland where the
      incidence of NKH is unusually high. The immunochemical and in situ hybridization
      analyses revealed that the strong GCS expression was observed in rat hippocampus,
      olfactory bulbus, and cerebellum. The distribution resembled that of N-methyl-D
      aspartic acid (NMDA) receptor which has binding site for glycine. It is,
      therefore, suggested that the neurological disturbance in NKH may be caused by
      excitoneurotoxicity through the NMDA receptor allosterically activated by high
      concentration of glycine. Based on the hypothesis the NMDA antagonists such as
      ketamine and dextromethorphan were administered to the patients. We treated three
      neonatal case with dextromethorphan and it ameliorated their findings on
      electroencephalogram and behavior in two out of three patients. Thus the GCS is
      suggested to play a role in regulation of glycine level around the NMDA receptor.

PMID- 9183996
TI  - Detection of the CTG repeat expansion in congenital myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is caused by an abnormal expansion of an unstable CTG
      trinucleotide repeat in the 3' untranslated region of mRNA encoding a putative
      serine/threonine protein kinase. We analyzed 59 patients with DM (28 congenital
      DM families: 27 families with maternal transmission and 1 paternal transmission)
      and 27 normal control subjects to evaluate their CTG repeat size between DM
      patients and the normal controls, and to search for a correlation between the
      clinical characteristics of congenital DM (CDM) and CTG repeat expansions.
      Analysis was on the basis of the Southern blot and polymerase chain reaction
      (PCR) methods, and by direct sequencing of PCR amplified CTG repeats. Analysis of
      intergenerational differences in the CTG repeat size for mother-child pairs
      showed a positive correlation (y = 1.0384x + 1265.2, r2 = 0.311). In addition to
      the strong parental bias, this group showed genetic anticipation. There was a
      significant correlation of the CTG repeat expansion with disease severity. The
      largest CTG repeat expansion (2,293 CTG repeats) on average belonged to the
      severe CDM group, and the smallest (129 CTG repeats) to the subclinical DM group.
      The mutant allele of an asymptomatic father in the paternally transmitted
      pedigree revealed 75 CTG repeats, demonstrating that he was a DM protomutation
      carrier.

PMID- 9183997
TI  - Biparental alleles of HLA-G are co-dominantly expressed in the placenta.
AB  - HLA-G is the only major histocompatibility complex molecule expressed in the
      human placenta and thus has been considered to be necessary for maintenance of
      pregnancy. We investigated whether HLA-G expression is regulated in a parent-of
      origin allele-specific manner. Of six first trimester and three third trimester
      placentas, three first trimester and two third trimester placentas showed
      heterozygosity at the PstI polymorphic site in the 3'-untraslated region. Reverse
      transcription-polymerase chain reaction (RT-PCR) analysis revealed biallelic
      expression of HLA-G in all the informative cases, indicating that HLA-G is not
      imprinted during the gestational period, at least at the transcriptional level.
      As HLA-G has been postulated to be polymorphic not only at the DNA sequence level
      but also at the peptide level, co-dominant expression of the gene suggests that
      each parental allele is involved in the allogenic response during pregnancy.

PMID- 9183998
TI  - Genotypes of aldehyde dehydrogenase and alcohol dehydrogenase polymorphisms in
      patients with Leber's hereditary optic neuropathy.
AB  - To define whether alcohol drinking provides a risk for Leber's hereditary optic
      neuropathy (LHON), the genotypes of low K(m) aldehyde dehydrogenase (ALDH2) and
      alcohol dehydrogenase type 2 (ADH2), major enzymes involving the alcohol
      metabolism, were examined in 29 unrelated Japanese patients with LHON associated
      with mitochondrial DNA 11778 mutation, 24 unrelated asymptomatic carriers with
      the mutation and 57 normal controls without the mutation. PCR-restriction
      detection revealed three genotypes of ALDH2 and ADH2. The allele frequencies of
      either enzyme in LHON patients, asymptomatic carriers, or both, did not differ
      from those in normal controls. There is no association between LHON and genotypes
      of alcohol-metabolizing enzymes. However, six of the LHON patients had frequent
      alcohol consumption, while none of the asymptomatic carriers claimed frequent
      drinking habit. Thus, we could not make a denial of drinking effects on optic
      nerve damage in LHON.

PMID- 9183999
TI  - GM and KM allotypes in eight tribal populations of Madyha Pradesh and Orissa,
      India.
AB  - Serum samples from eight endogamous Indian tribal populations of Madhya Pradesh
      (Dhurwa, Halba, Bhatra, Muria, Maria) and Orissa (Deshia Khond, Binjhal, Kisan)
      with a total of n = 731 unrelated individuals were typed for G1M (1,2,3,17), G3M
      (5,10,11,13,14,15,16,21, 26), and KM (1). In seven of these populations five
      different GM haplotypes were found: GM* 1,17;21,26; GM* 1,17;10,11,13,15,16; GM*
      1,2, 17;21,26; GM* 1,3;5,10,11,13,14,26; and GM* 3;5,10,11,13,14,26. In the Kisan
      sample the haplotype GM* 1,2,17;21,26 is absent. The intergroup variability in
      the distribution of these haplotypes is considerable and statistically highly
      significant. The reasons for that can be attributed to the ethnohistory and to
      the genetic isolation of these eight endogamous tribal populations. The GM
      haplotype distribution pattern of all these groups is quite different from that
      of the non-tribal populations of India, whereas it is in good agreement with that
      of the so far tested other tribal populations from India. This can be explained
      by different origin and history of the Indian tribal and non-tribal populations.
      In the KM system, too, remarkable variability is seen in the distribution of
      phenotype and allele frequencies among the eight tribal populations under study.

PMID- 9184000
TI  - Polymorphic and tissue-specific imprinting of the human Wilms tumor gene, WT1.
AB  - We previously demonstrated maternal monoallelic expression of the Wilms tumor
      suppressor gene, WT1, in about half of pre-term placental villus and fetal brain
      tissues examined. There were two alternative explanations for this pattern of the
      WT1 expression, i.e., an imprinting polymorphism vs. a developmental stage
      dependent switching from monoallelic to biallelic expression of the gene. To
      investigate these possibilities, we examined WT1 expression in a larger number of
      villus samples (46 samples) with gestational ages ranging from 4 to 21 weeks,
      using reverse transcriptase-based polymerase chain reaction (RT-PCR) to amplify
      the sequences for polymorphic sites in the 3'-untranslated region (UTR) of WT1.
      Maternal monoallelic expression was observed in 7 (39%) of 18 samples informative
      for the polymorphism, while the expression of the remaining 11 samples was
      biallelic. In addition, there was no correlation between expression patterns and
      gestational ages of the samples. The results indicate that the pattern of
      expression (monoallelic vs. biallelic) is polymorphic. The expression patterns
      were also studied in five different organs from a 21-week-old fetus, showing
      monoallelic expression only in the placenta and biallelic expression in other
      organs (heart, lung, liver and intestine). The finding supports the tissue
      specificity of the WT1 monoallelic expression.

PMID- 9184001
TI  - Assignment of the human connexin43 gene, GJA1, to chromosome 6q22.3.
AB  - Connexin43 is one of connexin proteins which make up the intercellular gap
      junctions. Targeted null mutation of the mouse connexin43 gene has been reported
      to result in a cardiac malformation. Moreover, single-base mutations of the human
      homolog (GJA1) were identified in patients with laterality defects of the chest
      and abdominal organs, suggesting that connexin43 contributes to the determination
      of laterality during organogenesis. We mapped GJA1 to 6q22.3 by fluorescence in
      situ hybridization, using a bacterial artificial chromosome (BAC) clone that
      covered almost the entire GJA1-cDNA, as a probe.

PMID- 9184002
TI  - A keratin K10 gene mutation in a Japanese patient with epidermolytic
      hyperkeratosis.
AB  - Epidermolytic hyperkeratosis (EHK), or bullous congenital ichthyosiform
      erythroderma, is characterized by generalized erythroderma, ichthyosiform skin
      and blistering, and is caused by an aberration of the keratin intermediate
      filaments. In this study, we examined keratin K10 and 1 gene mutations in a
      Japanese EHK patient who had severe ichthyosiform erythroderma at birth and
      developed subsequent blistering. The patient had a G to A transition at codon 156
      of the keratin K10 gene, which resulted in an arginine (Arg)-->histidine (His)
      substitution in the helix initiation peptide of the highly-conserved 1A domain in
      keratin K10. This is the first mutation report of a Japanese patient with EHK,
      although the position and mode of the mutation identified here did not differ
      from those in reported Western cases.

PMID- 9184003
TI  - Identification of an HLA-DQ6-derived peptide recognized by mouse MHC class I H
      2Db-restricted CD8+ T cells in HLA-DQ6 transgenic mice.
AB  - CD8+ T cells from C57BL/6(B6) mice show cytotoxicity to B cell blasts prepared
      from syngeneic transgenic mice expressing HLA-DQ6 molecules in a mouse MHC class
      I H-2Db restricted manner. Although these results suggest that CD8+ T cells
      recognize peptides derived from DQ6 molecule bound to H-2Db on target cells, no
      direct evidence so far has been obtained. To clarify this, we synthesized 23
      peptides corresponding to DQ6 alpha or beta chain and carrying the motifs of Db
      binding peptides, and examined their capacity to induce cytotoxicity in the CD8+
      T cell line. We show here that DQA1-2, one of these peptides, induced
      cytotoxicity of the CD8+ T cells when this peptide was pulsed to H-2Db expressing
      target cells, as efficiently as HLA-DQ6 expressing target cells did. Thus, our
      results suggest that DQA1-2 can be naturally processed from DQ6 molecules and
      recognized by the CD8+ T cells in the context of H-2Db molecules. These results
      suggest that allogeneic HLA class II molecules are involved in the rejection not
      only as the ligand for T cell receptor of alloreactive CD4+ T cells but also as
      self-peptides bound to HLA class I molecules recognized by CD8+ T cells.

PMID- 9184004
TI  - Deletion of twenty seven nucleotides within exon 11 of the band 3 gene identified
      in ovalocytosis in Lombok Island, Indonesia.
AB  - This study reports the molecular characterization of ovalocytosis in Lombok
      Island, Indonesia. The analysis of genomic DNA by polymerase chain reaction shows
      that all 21 ovalocytotic individuals have two amplified products of different
      size from a region encompassing exon 11 of the band 3 gene. The sequence of the
      larger product matched perfectly with that of normal individuals. In the sequence
      of the smaller product, 27 nucleotides within exon 11 were deleted. The
      heterozygous presence of the deletion identified in other parts of Southeast Asia
      was confirmed in patients with ovalocytosis in an isolated island of eastern
      Indonesia.

PMID- 9184005
TI  - Assignment of the human UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase
      type-2 gene to chromosomal region 1q42 by fluorescence in situ hybridization.

PMID- 9184006
TI  - NcoI restriction fragment length polymorphism at -308 of the tumor necrosis
      factor alpha (TNFA) promoter region in Korean.
AB  - Tumor necrosis factor alpha (TNFA) is a cytokine, which is secreted from
      activated macrophage, with a broad range of biological activities. The gene
      encoding TNFA is located in tandem with the TNFB gene within the HLA complex on
      chromosome 6p21.3. We detected a single base polymorphism in the human TNFA gene
      promoter region in 300 unrelated Korean individuals. The TNFA promoter region
      which showed a G to A transition at position of -308 was investigated by NcoI
      restriction fragment length polymorphism analysis. A biallelic polymorphism of
      TNFA gene showed fragments of 87/20 bp and 107 bp acting as TNFA*1 allele and
      TNFA*2 allele, respectively. The allele frequencies of TNFA*1 and TNFA*2 were
      0.8783 and 0.1217, respectively. The 21.7% of heterozygosity was observed. No
      association between promoter region phenotypes of TNFA and the first intron
      phenotypes of TNFB was observed in Korean. Allele frequencies of Koreans were
      compared with that of Europeans.

PMID- 9184007
TI  - Fate and activity of microorganisms introduced into soil.
AB  - Introduced microorganisms are potentially powerful agents for manipulation of
      processes and/or components in soil. Fields of application include enhancement of
      crop growth, protection of crops against plant-pathogenic organisms, stimulation
      of biodegradation of xenobiotic compounds (bioaugmentation), and improvement of
      soil structure. Inoculation of soils has already been applied for decades, but it
      has often yielded inconsistent or disappointing results. This is caused mainly by
      a commonly observed rapid decline in inoculant population activity following
      introduction into soil, i.e., a decline of the numbers of inoculant cells and/or
      a decline of the (average) activity per cell. In this review, we discuss the
      available information on the effects of key factors that determine the fate and
      activity of microorganisms introduced into soil, with emphasis on bacteria. The
      factors addressed include the physiological status of the inoculant cells, the
      biotic and abiotic interactions in soil, soil properties, and substrate
      availability. Finally, we address the possibilities available to effectively
      manipulate the fate and activity of introduced microorganisms in relation to the
      main areas of their application.

PMID- 9184008
TI  - Common themes in microbial pathogenicity revisited.
AB  - Bacterial pathogens employ a number of genetic strategies to cause infection and,
      occasionally, disease in their hosts. Many of these virulence factors and their
      regulatory elements can be divided into a smaller number of groups based on the
      conservation of similar mechanisms. These common themes are found throughout
      bacterial virulence factors. For example, there are only a few general types of
      toxins, despite a large number of host targets. Similarly, there are only a few
      conserved ways to build the bacterial pilus and nonpilus adhesins used by
      pathogens to adhere to host substrates. Bacterial entry into host cells
      (invasion) is a complex mechanism. However, several common invasion themes exist
      in diverse microorganisms. Similarly, once inside a host cell, pathogens have a
      limited number of ways to ensure their survival, whether remaining within a host
      vacuole or by escaping into the cytoplasm. Avoidance of the host immune defenses
      is key to the success of a pathogen. Several common themes again are employed,
      including antigenic variation, camouflage by binding host molecules, and
      enzymatic degradation of host immune components. Most virulence factors are found
      on the bacterial surface or secreted into their immediate environment, yet
      virulence factors operate through a relatively small number of microbial
      secretion systems. The expression of bacterial pathogenicity is dependent upon
      complex regulatory circuits. However, pathogens use only a small number of
      biochemical families to express distinct functional factors at the appropriate
      time that causes infection. Finally, virulence factors maintained on mobile
      genetic elements and pathogenicity islands ensure that new strains of pathogens
      evolve constantly. Comprehension of these common themes in microbial
      pathogenicity is critical to the understanding and study of bacterial virulence
      mechanisms and to the development of new "anti-virulence" agents, which are so
      desperately needed to replace antibiotics.

PMID- 9184014
TI  - Prevalence of stroke in two samples (rural and urban) of old people in Spain. A
      pilot door-to-door study carried out by health professionals.
AB  - The aim of this study was to present the prevalence of stroke from a pilot study
      in old people. The urban site sample (Madrid) was made up of 397 subjects and the
      rural site sample (Arevalo, Avila) of 862 subjects. The study was performed with
      a door-to-door methodology. In the urban sample, the prevalence of stroke was
      8.5% (CI 95% = 5.5-11.5%) and that of TIA was 2.1% (CI 95% = 0.6-3.6%). In the
      rural location the prevalence of stroke was 7.1% (CI 95% = 5.4-8.8%). This
      prevalence of stroke is higher than in other Spanish studies. These results need
      to be confirmed in a wider investigation.

PMID- 9184009
TI  - Macrophages in resistance to candidiasis.
AB  - Candida albicans, an increasingly common opportunistic pathogenic fungus,
      frequently causes disease in immunodeficient but not immunocompetent hosts.
      Clarifying the role of the phagocytic cells that participate in resistance to
      candidiasis not only is basic to understanding how the host copes with this
      dimorphic pathogen but also will expedite the development of innovative
      prophylactic and therapeutic approaches for treating the multiple clinical
      presentations that candidiasis encompasses. In this review, we present evidence
      that a diverse population of mononuclear phagocytes, in different states of
      activation and differentiation and from a variety of host species, can
      phagocytize C. albicans blastoconidia via an array of opsonic and nonopsonic
      mechanisms and can kill C. albicans blastoconidia and hyphae by means of oxygen
      dependent and -independent mechanisms. Reactive nitrogen intermediates should now
      be added to the well-established candidacidal reactive oxygen intermediates of
      macrophages. Furthermore, what were thought to be two independent pathways, i.e.,
      nitric oxide and superoxide anion, have now been shown to combine to form a
      potent macrophage candidacidal molecule, peroxynitrite. In contrast to monocytes
      and neutrophils, which are important in resistance to early stages of C. albicans
      infections, more differentiated macrophages activated by cytokines such as gamma
      interferon participate in the acquired resistance of hosts with C. albicans
      specific, cell-mediated immunity. Evidence presented in this review demonstrates
      that mononuclear phagocytes, in some instances in the absence of other
      professional phagocytes such as neutrophils, play an import role in resistance to
      systemic and mucosal candidiasis.

PMID- 9184012
TI  - The first living systems: a bioenergetic perspective.
AB  - The first systems of molecules having the properties of the living state
      presumably self-assembled from a mixture of organic compounds available on the
      prebiotic Earth. To carry out the polymer synthesis characteristic of all forms
      of life, such systems would require one or more sources of energy to activate
      monomers to be incorporated into polymers. Possible sources of energy for this
      process include heat, light energy, chemical energy, and ionic potentials across
      membranes. These energy sources are explored here, with a particular focus on
      mechanisms by which self-assembled molecular aggregates could capture the energy
      and use it to form chemical bonds in polymers. Based on available evidence, a
      reasonable conjecture is that membranous vesicles were present on the prebiotic
      Earth and that systems of replicating and catalytic macromolecules could become
      encapsulated in the vesicles. In the laboratory, this can be modeled by
      encapsulated polymerases prepared as liposomes. By an appropriate choice of
      lipids, the permeability properties of the liposomes can be adjusted so that
      ionic substrates permeate at a sufficient rate to provide a source of monomers
      for the enzymes, with the result that nucleic acids accumulate in the vesicles.
      Despite this progress, there is still no clear mechanism by which the free energy
      of light, ion gradients, or redox potential can be coupled to polymer bond
      formation in a protocellular structure.

PMID- 9184010
TI  - Nucleocytoplasmic transport of macromolecules.
AB  - Nucleocytoplasmic transport is a complex process that consists of the movement of
      numerous macromolecules back and forth across the nuclear envelope. All
      macromolecules that move in and out of the nucleus do so via nuclear pore
      complexes that form large proteinaceous channels in the nuclear envelope. In
      addition to nuclear pores, nuclear transport of macromolecules requires a number
      of soluble factors that are found both in the cytoplasm and in the nucleus. A
      combination of biochemical, genetic, and cell biological approaches have been
      used to identify and characterize the various components of the nuclear transport
      machinery. Recent studies have shown that both import to and export from the
      nucleus are mediated by signals found within the transport substrates. Several
      studies have demonstrated that these signals are recognized by soluble factors
      that target these substrates to the nuclear pore. Once substrates have been
      directed to the pore, most transport events depend on a cycle of GTP hydrolysis
      mediated by the small Ras-like GTPase, Ran, as well as other proteins that
      regulate the guanine nucleotide-bound state of Ran. Many of the essential factors
      have been identified, and the challenge that remains is to determine the exact
      mechanism by which transport occurs. This review attempts to present an
      integrated view of our current understanding of nuclear transport while
      highlighting the contributions that have been made through studies with genetic
      organisms such as the budding yeast, Saccharomyces cerevisiae.

PMID- 9184013
TI  - Energetics of syntrophic cooperation in methanogenic degradation.
AB  - Fatty acids and alcohols are key intermediates in the methanogenic degradation of
      organic matter, e.g., in anaerobic sewage sludge digestors or freshwater lake
      sediments. They are produced by classical fermenting bacteria for disposal of
      electrons derived in simultaneous substrate oxidations. Methanogenic bacteria can
      degrade primarily only one-carbon compounds. Therefore, acetate, propionate,
      ethanol, and their higher homologs have to be fermented further to one-carbon
      compounds. These fermentations are called secondary or syntrophic fermentations.
      They are endergonic processes under standard conditions and depend on intimate
      coupling with methanogenesis. The energetic situation of the prokaryotes
      cooperating in these processes is problematic: the free energy available in the
      reactions for total conversion of substrate to methane attributes to each partner
      amounts of energy in the range of the minimum biochemically convertible energy,
      i.e., 20 to 25 kJ per mol per reaction. This amount corresponds to one-third of
      an ATP unit and is equivalent to the energy required for a monovalent ion to
      cross the charged cytoplasmic membrane. Recent studies have revealed that
      syntrophically fermenting bacteria synthesize ATP by substrate-level
      phosphorylation and reinvest part of the ATP-bound energy into reversed electron
      transport processes, to release the electrons at a redox level accessible by the
      partner bacteria and to balance their energy budget. These findings allow us to
      understand the energy economy of these bacteria on the basis of concepts derived
      from the bioenergetics of other microorganisms.

PMID- 9184015
TI  - Duplex PCR of the Y-27H39 and HPRT loci with reference to Japanese population
      data on the HPRT locus.
AB  - Using a duplex polymerase chain reaction (PCR) system, we successfully amplified
      GATA microsatellite loci Y-27H39 and HPRT on the Y and X chromosomes,
      respectively, and detected their alleles with a digoxigenin-labeled (GATA)6
      probe. Among 450 unrelated Japanese including 225 females, we found 6 HPRT
      alleles ranging from 155 to 175 nucleotides with a simple repeat structure
      comprising 11 to 16 repeats. The duplex PCR is highly informative in Japanese.

PMID- 9184011
TI  - Stable DNA replication: interplay between DNA replication, homologous
      recombination, and transcription.
AB  - Chromosome replication in Escherichia coli is normally initiated at oriC, the
      origin of chromosome replication. E. coli cells possess at least three additional
      initiation systems for chromosome replication that are normally repressed but can
      be activated under certain specific conditions. These are termed the stable DNA
      replication systems. Inducible stable DNA replication (iSDR), which is activated
      by SOS induction, is proposed to be initiated from a D-loop, an early
      intermediate in homologous recombination. Thus, iSDR is a form of recombination
      dependent DNA replication (RDR). Analysis of iSDR and RDR has led to the proposal
      that homologous recombination and double-strand break repair involve extensive
      semiconservative DNA replication. RDR is proposed to play crucial roles in
      homologous recombination, double-strand break repair, restoration of collapsed
      replication forks, and adaptive mutation. Constitutive stable DNA replication
      (cSDR) is activated in mhA mutants deficient in RNase HI or in recG mutants
      deficient in RecG helicase. cSDR is proposed to be initiated from an R-loop that
      can be formed by the invasion of duplex DNA by an RNA transcript, which most
      probably is catalyzed by RecA protein. The third form of SDR is nSDR, which can
      be transiently activated in wild-type cells when rapidly growing cells enter the
      stationary phase. This article describes the characteristics of these alternative
      DNA replication forms and reviews evidence that has led to the formulation of the
      proposed models for SDR initiation mechanisms. The possible interplay between DNA
      replication, homologous recombination, DNA repair, and transcription is explored.

PMID- 9184016
TI  - [Demonstration of heat shock protein, ubiquitin, in fire death autopsy cases by
      immunohistochemical study].
AB  - The expression of ubiquitin in heart, lung, liver, kidney and adrenal gland, was
      immunohistochemically studied in 23 autopsy cases died by fire accident. There
      were no correlations between the localization of ubiquitin in each organ, and
      burn extent, and burn degree, and carboxyhemoglobin (COHb) saturation. In serious
      tracheal burn cases, strong immunoreactivities of ubiquitin were observed in the
      lung. On the other hand, in cases of high concentration of cyanide, the ubiquitin
      immunostaining in the lungs was weak. These results indicate that in fire death
      cases, the expression of ubiquitin is affected by cyanide. In many cases strong
      immunoreactivities of ubiquitin were found in the adrenal glands, suggesting that
      the adrenal gland reacts strongly to the heat shock. Only three out of 23 autopsy
      cases showed the negative staining of ubiquitin immunoreactivity. Probably this
      is resulted from the early death prior to the expression of ubiquitin.

PMID- 9184017
TI  - Astrocytic reaction in long-term resuscitation.
AB  - The brain of 34 subjects who died after prolonged resuscitation (more than 20
      days) were studied in order to evaluate the possibility of discriminating
      original cerebral injuries from changes caused by prolonged resuscitation. We
      focused our attention on the astrocytic reaction and its relationship to the
      associated lesions. Twelve of the 34 cases showed astrocytosis picture. Of these
      5 were anisomorphic and 7 isomorphic. From the analysis of the various
      morphological findings, taking into account an individual's clinical history, we
      can conclude that isomorphic astrocytosis is a typical morphological reaction
      related to resuscitation duration and it is the result of a slow, gradual
      neuronal degeneration induced by chronic hypoxia. Anisomorphic astrocytosis, on
      the other hand, can be an indicator of acute and focal cerebral lesion.

PMID- 9184018
TI  - Detection of drugs and poisons in postmortem tissues--determination of paraquat
      in tissues of rabbits buried underground.
AB  - The possibility of detecting paraquat in tissues of rabbits buried underground
      over a 2-year period was examined. Paraquat (1.2 g) was given orally to rabbits,
      which were sacrificed 1 h after administration. The animals were buried
      underground, and the skeletal muscles and the bones were collected 3 and 6 months
      after death, and 3, 6, 12, and 24 months after death, respectively. Paraquat was
      present in all bone marrow samples, showing a slight decrease in concentration
      until 12 months. Paraquat was also detected in all skeletal muscle samples,
      showing almost no change in concentration until 6 months. These results indicate
      that intoxication with paraquat as well as the degree of poisoning can both be
      determined from the skeletal muscles and bone marrow of cadavers which have been
      buried underground for a long period of time even in human cases.

PMID- 9184019
TI  - Estimation of sex and age by calcification pattern of costal cartilage in
      Japanese.
AB  - The right 4th costal cartilages of 110 Japanese cadavers (55 males and 55
      females) were radiographically examined to elucidate the sex differences in the
      pattern of calcification. Calcification was observed in the cartilages of both
      sexes aged over 20 years. Twenty out of 98 subjects showed no calcification
      despite being over 20 years old; so calcification at this site did not occur with
      aging in all adults, but was seen in approximately 80%. Calcification showed 3
      patterns, which were marginal, central, and granular calcification pattern. The
      marginal pattern was observed in 39 subjects (33 males and 6 females), the
      central pattern in 15 (all female) and the granular pattern in 20 (1 male and 19
      females). Detailed investigation of the internal structure at the distal ends of
      the ribs and the shape of the costochondral junction revealed better estimates of
      age compared with the degree of calcification alone, which showed wide individual
      variation. Radiographic examination of the costal cartilages is useful and
      conveniet for estimating the sex and age, not only of fragmentary and partial
      remains, but also of skeletons or badly decomposed bodies. Moreover, it may be
      effective as a screening test for identification after large-scale disasters.

PMID- 9184020
TI  - [A suicidal case of electrocution with hypnotic drug poisoning: an autopsy
      report].
AB  - A 28-year-old male was found dead on a bed in a hotel. He had two electric wires,
      the ends of which were fastened to each coin (50 and 100 yen); the coins were
      attached to a left hypochondrial region and a left side of the chest. The other
      ends of the wires were connected to a time switch, which had been connected to a
      plug top (100 V, 60 Hz alternating current). An empty box of a commercially
      available hypnotic (bromvalerylurea), a suicide note and a manual book for
      suicide were found at the spot. As autopsy findings, both burns on the left
      hypochondrial region and on the left side of the chest were carbonized at their
      central parts and erythemas were also noted around them. Histological findings
      were consistent with electric marks and the burns showed vital reactions. Copper
      stain was slightly positive; iron stain was negative. Bromvalerylurea
      concentrations in blood, urine, brain, liver and kidney samples were 14.5, 37.7,
      5.8, 5.2 and 6.2 micrograms/ml or g, respectively. The blood level showed that he
      had been moderately intoxicated by the drug, but not fatal. The cause of death
      was thus judged to be suicidal electrocution. It seems that suicide was
      influenced by a "Manual Book of Suicide", which was found in his bag.

PMID- 9184021
TI  - Sudden death due to diabetic coma in insulin-department diabetes mellitus: an
      autopsy report.
AB  - Sudden death caused by the acute onset of diabetic coma is reported. A 15-year
      old female had been suffering from insulin-dependent diabetes mellitus for the
      prior 8 years and had a fever and vomiting for the past few days. On the 4th day,
      after the onset of fever and vomiting, she died suddenly, and was autopsied to
      clarify the cause of death. Macroscopic examination revealed that the pancreas
      was atrophic (40 g) whereas the liver was markedly enlarged (2,740 g).
      Histological findings were: 1) The islets of Langerhans were decreased in size
      and number. They were not positive for aldehyde-fuchsin staining, 2) There were
      severe fatty changes in the liver cells. The retained blood in the left ventricle
      was analyzed: glucose, 1,016 mg/dl; acetone, 345 mg/l; acetoacetate, 5.91 mmol/l:
      D-3-hydroxybutyrate, 4.17 mmol/l; hemoglobin A1c, 10.2%; fructosamine, 416
      mumol/l; total serum cholesterol, 220 mg/dl; triglycerides, 205 mg/dl; free fatty
      acid, 8.0 mEq/l; urea nitrogen, 40 mg/dl. Although the biochemical estimation of
      the glucose and ketone levels in post-mortem body fluids was recognized as being
      unreliable, many of these values were far elevated in comparison with those of
      normal individuals. Thus, we concluded that the cause of death was diabetic
      ketoacidosis. We also discuss the diagnostic problems of postmortem blood
      chemistry.

PMID- 9184022
TI  - A fatal case of drinking and cyanamide intake.
AB  - A 34-year-old housewife with alcohol dependence vomited severely, lost
      consciousness, and died after she took more than 20 ml of 1% calcium cyanamide,
      and alcoholic beverage containing about 129 g of ethyl alcohol. An autopsy was
      performed around 16 h after death. The body weighed 55.5 kg, and moderate lung
      edema was found. Ethanol concentrations were 4.24 mg/g in the left heart blood,
      4.39 mg/g in the right heart blood, and 21.55 mg/g in the stomach contents.
      Cyanamide concentrations were 0.63 microgram/g in the left heart blood, 0.20
      microgram/g in the right heart blood, and 0.22 microgram/g in the stomach
      contents. The cause of death was determined to be acute ethanol intoxication with
      alcohol-cyanamide reaction.

PMID- 9184023
TI  - [Report on medico-legal data from the mass-investigation performed by the Medico
      Legal Society of Japan (XIV). Autopsy cases of traffic accidents in Japan (1990
      1994). Planning and Development Committee of The Medico-Legal Society of Japan].
AB  - Autopsy findings in 3, 185 cases of death due to traffic accidents obtained from
      all institutions belong to the Medico-Legal Society of Japan between 1990 and
      1994 were analyzed statistically. The results are summarized as follows: 1) The
      annual number of autopsy cases related to traffic accidents was stable and
      accounted for 10% of all autopsy cases examined. The autopsy cases also accounted
      for only 6% of all deaths due to traffic accidents. Cases requiring judicial
      autopsy are few despite the fact that deaths due to traffic accidents are
      considered deaths resulting from professional negligence. 2) The purposes of
      autopsy were, in a decreasing order of frequency, (1) to examine whether the
      accident was a hit-and-run case, (2) to examine whether the case was multiple
      accidents, and (3) to clarify the relationship of death with the accident. 3)
      According to the age, those who were involved in accidents while they were on
      foot overwhelmingly aged 70 years or above, and those who were involved in
      accidents while they were riding motorcycles were predominantly in their teens to
      the 20's. Concerning the situation of the accident, run-over cases, were
      frequently those in their 40's, and collision cases were predominantly those in
      their 70's. Among those who died in cars, the drivers were most frequently those
      in their 50's, followed by those in their 20's. 4) The degree of external and
      internal injuries was compared. About half the victims sustained severe injuries
      both internally and externally, and the remaining half sustained mild external
      injuries and severe internal injuries. Run-over cases generally had severe
      injuries both internally and externally, but collision cases tended to have mild
      external injuries and severe internal injuries. 5) The most frequent cause of
      death was brain injury, followed by loss of blood and traumatic shock. 6) Tire
      marks were observed in 23% of the run-over cases, and they were observed in the
      head, face, neck, and thoracoabdominal region in most cases. 7) Of the collision
      cases, collision injuries were observed in 55.6%, and the sites of collision
      injuries were the crural and femoral regions. 8) Of those who died in the car,
      about 46% were the drivers. 9) Deaths while driving due to internal causes
      accounted for 3% of all autopsy cases who died in traffic accidents, and ischemic
      heart disease was the most frequent of the internal causes. 10) Concerning
      injuries caused by safety devices, 3.5% of the drivers and 4.4% of non-driver
      passengers were injured by the seat belts, and 3.9% of those who were riding
      motorcycles were injured by the helmets. 11) Alcohol was detected from 47.7% of
      the cadavers examined, and the alcohol level was 0.5 mg/ml or above in 19% of
      those driving and 50.2% of those on foot. 12) Stimulants were detected in 5
      (3.8%) of 132 cases examined, and thinner was detected in 17 (13.0%) of 131 cases
      examined.

PMID- 9184024
TI  - [Report on medico-legal data from the mass-investigation performed by The Medico
      Legal Society of Japan (XV). Autopsy cases of therapeutic complications and other
      medical misadventures in Japan (1981-1991). Planning and Development Committee of
      The Medico-Legal Society of Japan].
AB  - As the continuation of the previous report covering the period of 5 years (1976
      1980) from the Medico-Legal Society of Japan, a statistical study was made of
      therapeutic fatal complications examined by forensic pathologists in Japan in the
      11 year period between 1981 and 1991. The total number of the cases obtained was
      315, composed of 179 male and 136 female cases. Eighty cases (male 33, female 47)
      were associated with anesthesia, 74 (53, 21) with injections except anesthetics,
      31 (13, 18) with operations, labor and clinical examinations, and 14 (9, 5) with
      drug administration or inhalation of drugs, respectively. Three cases were
      associated with blood transfusion and other 3 cases with hemodialysis. Fifteen
      patients died owing to erroneous diagnosis at the first medical examination.
      There were 9 cases of drug misuse, of which 7 cases were administered drugs
      through a wrong route and 2 were carelessly given a drug different from
      prescription. Miscellaneous cases where autopsy revealed diseases, nursing
      mishaps, etc. to account for death were 86 (51, 35) in number. Except for the
      miscellaneous cases, the number of therapeutic fatal complications tends to
      decrease gradually in comparison with that of the preceding 5 years (1976-1980).
      Medical practitioners should especially be aware of a slightly large number of
      the deaths associated with wrong diagnosis as well as those with anesthesia,
      injections and operations, labor and clinical examinations.

PMID- 9184025
TI  - [Ultrastructure of the mucous membrane of the human newborn vocal folds].
AB  - This study was carried out to determine the ultrastructure of the mucous membrane
      of vocal folds of human newborns. Excised larynges of newborns were observed with
      a transmission electron microscope. The results obtained are summarized as
      follows: 1) The epithelium of the edge of the vocal folds consisted of stratified
      squamous epithelium. It was thin but numerous desmosomes showed firm attachment
      between cells. 2) The basement membrane zone had the same structure as that of
      adults. 3) The lamina propria of the vocal fold mucosa was loose in structure and
      there was no vocal ligament. 4) Fibroblasts were sparse and in the resting phase.
      5) Collagenous and elastic fibers were sparse in the lamina propria. Structures
      of the the collagenous fibers wee mature but those of elastic fibers, were
      immature morphologically. 6) Ground substance was abundant in the lamina propria.
      7) The newborn vocal fold mucosa lacked not only a vocal ligament but also
      adequate viscoelasticity for vibration.

PMID- 9184026
TI  - [Clinical and histopathological studies of granular cell tumor of the tongue].
AB  - We studied the clinical and histopathological characteristics of granular cell
      tumor (GCT) of the tongue in 5 cases (2 males and 3 females) over a period of 25
      years. The patients ranged in age from 8 to 44 years old. In 4 cases, the site of
      origin in the tongue was the anterior two thirds of the lateral border (UICC). In
      the remaining case, the tumor originated on the dorsal surface of the tongue
      (UICC). The tumor was 3-10 mm long and had an average diameter of 6mm. The
      lesions were painless. The cellular granules in all the tumors reacted positively
      to PAS regent and S-100 protein using immunohistological methods. Other
      immunohistological staining using anti-actin antibody showed cellular granules
      beneath the epithelium. In one case, these findings were especially marked in the
      portion that exhibited pseudo-epitheliomatous hyperplasia. There was a mixture of
      both positive and negative cells in the deep layer of the epithelium. Not all
      tumor cells stained with anti-desmin antibody, however, there appeared to be a
      direct transitions from stained striated muscle fibers to the tumor cells.
      Staining with anti-vimentin antibody was positive at the boundaries between cells
      and the positive granules in cells appeared in the dots. Two of the five, tumors
      were unencapsulated, and the other 3 were partially encapsulated. The constituent
      fibers of the capsule consisted of collagen fibers alone. Thus, the former 2
      cases should be regarded as proliferative in nature, and the latter 3 as benign.
      These tumor cells were potentially very active beneath the epithelium. From the
      results of our immunohistological stainings, we concluded that myoepithelial
      cells might also be the source of GCT cells, although GCT cells have generally
      been reported to originate from muscle and nerve cells. We maintain that care
      must be taken when removing GCTs because there may be proliferative growth along
      the epithelium.

PMID- 9184027
TI  - [Clinical study in vertiginuous patients suspected of having neurovascular
      compression syndrome of the eighth cranial nerve].
AB  - Neurovascular compression syndrome of the 5th and 7th cranial nerves has been
      recognized as the cause of trigeminal neuralgia and hemifacial spasm. On the
      other hand, it is still difficult to diagnose vertigo as neurovascular
      compression syndrome of the 8th cranial nerve. To detect some specific finding in
      this syndrome of the 8th cranial nerve, 5 patients with vertigo with hemifacial
      spasm were examined for the clinical course and neuro-otological features. In all
      patients MRI and/or angiography suggested vascular compression against the 8th
      cranial nerve. The clinical courses of these patients revealed various symptoms
      resembling benign paroxysmal positional vertigo, vestibular neuronitis and
      Meniere's disease. Audiograms showed two normal hearing patterns, bilateral high
      frequency hearing loss probably due to aging in one case, bilateral C5-dip in one
      and fluctuating unilateral hearing loss like Meniere's disease in one. The
      prolongation of IPL I-III on auditory brainstem response proposed as a criterion
      by Moller was detected in one case. No response in the caloric test was found in
      two cases. These abnormalities in the auditory brainstem response and caloric
      test appeared to be useful for diagnosis but were uncommon findings in all cases.
      Electronystagmographic examinations including the eye tracking test, optokinetic
      nystagmus and optokinetic pattern were all normal. We could not find any specific
      clinical findings valuable for diagnosis of neurovascular compression syndrome of
      the 8th cranial nerve. It is proposed that the indication of microvascular
      decompression should be decided carefully.

PMID- 9184028
TI  - [Age-related development of the arrangement of connective tissue fibers in the
      lamina propria of the human vocal folds--scanning electron microscopic
      examination with digestion method].
AB  - The lamina propria of the human vocal fold consists of a superficial,
      intermediate, and deep layer. This stratified structure is thought to facilitate
      phonation. Each layer has different physical properties based on different
      alignment and distribution of collagen and elastic fibers. In the present study,
      developmental changes in vocal fold structure were studied in human fetuses,
      infants, and children, with special reference to the pattern of distribution of
      collagen and elastic fibers. Vocal fold specimens were obtained at autopsy from 5
      fetuses, 7 neonates, 3 infants, 3 children at the age of 1 year, 3 children at 3
      years, 3 children at 5 years, 3 children at 12 years, and 5 subjects at ages
      ranging from 15 to 22 years. Prior to the examination of collagen fibers, elastic
      fibers and cells were dissolved with 10% sodium hydroxide treatment. Prior to the
      examination of elastic fibers, collagen fibers and cells were dissolved by
      treatment with 90% formic acid. The specimens were then dehydrated, dried, ion
      coated with platinum, and examined with a scanning electron microscope. In
      fetuses and infants, thin, coiled fibers were found distributed densely in the
      anterior, posterior, and deep parts of the lamina propria, while irregular thick
      fibers were sparsely seen in the superficial layer of the vocal fold. In children
      aged 1 to 3 years, the dense fibers in the deep part decreased, and the
      longitudinal fibers in the superficial layer increased. In children at 5 years of
      age, longitudinal collagen and elastic fibers were noted in all of the layers of
      the vocal fold. The distribution of fibers was uniform irrespective of the depth.
      At 12 years of age, thin, coiled fibers were noted in the superficial layer,
      while thin, irregular fibers were found in the deep layer. At 17 years,
      differentiation of the superficial and deep layers was more evident. In male
      subjects after adolescence the curvature of curly collagen fibers decreased, and
      the diameter of fibers increased. The present findings suggest that the
      development of the vocal fold in childhood occurs in two steps. In the first
      step, dense fibers in the anterior, posterior, and deep parts of the lamina
      propria found in fetuses and infants shift to the anterior and posterior ends of
      the vocal fold, between which longitudinal fibers appear. During this step only
      simple phonation is possible. In the second step, differentiation of the
      superficial and deep layers occurs, and the stratified structure of the vocal
      fold appears in the teens. This step is probably related to the complicated
      modality of phonation in this age group. In males, the development of the vocal
      fold is completed after changes in collagen fibers during the mutation.

PMID- 9184029
TI  - [Immunohistological study of the nasal mucosa with reference to gamma delta-T
      cells].
AB  - The distribution of gamma delta-T cells (gamma delta-TCR positive cells) in nasal
      mucosa and polyps was studied in patients with nasal allergy and non-allergic
      patients. The biopsy specimens from the inferior turbinate and resected polyps
      were frozen at -70 degrees C and sliced at a thickness of 4 microns with a
      cryostat. Monoclonal antibodies (CD3 and TCR-gamma delta-1) and the Labelled
      Streptavidin Biotin method were used to detect T lymphocytes and gamma delta-T
      cells. The results were as follows: 1) The rate of gamma delta-T cells in the
      epithelium is higher than that in the lamina propria in patients with nasal
      allergy. 2) In non-allergic patients, on the other hand, the rate of gamma delta
      T cells was almost the same in these layers. 3) The distribution of gamma delta-T
      cells in nasal polyps was uniform and their rate was relatively high. It has been
      reported that gamma delta-T cells can recognize a stress antigen such as heat
      shock protein. These cells are thought to play an important role in non-specific
      immunoreactions. This study suggests that gamma delta-T cells in the nasal mucosa
      play an important role also in specific immunoreactions.

PMID- 9184030
TI  - [Clinical study of acute supraglottitis as a disease entity].
AB  - Adult supraglottitis is an acute inflammation of the supraglottic structures
      first reported by Shapiro et al. While multiple anatomical sites in the larynx
      and oropharynx are inflamed, the epiglottis is not always the most involved area.
      In this paper, we refer to "adult supraglottitis" as "acute supraglottitis"
      because pediatric supraglottitis is rare in Japan. There have been no reports of
      acute supraglottitis in Japan to date. We report a clinical study of 15 cases of
      acute supraglottitis. In addition, we investigated whether acute supraglottitis
      can be recognized as a special form of acute laryngitis, the same as
      epiglottitis. Thirteen of 15 patients had severe sore throat or pain on
      swallowing. Oropharyngeal and laryngeal examinations revealed that the most
      involved area in the oropharynx and larynx was the aryepiglottic folds and the
      arytenoids. Five patients with edema extending from the aryepiglottic folds to
      the arytenoids complained of referred otalgia on swallowing. Strep. Pyogenes,
      Strep, pneumoniae, alpha-strep., and Staph aureus were isolated from the
      oropharynx. All patients were hospitalized because of severe presenting symptoms.
      Treatment consisted of intravenous antibiotics, including piperacillin,
      clindamycin, flomoxef, aspoxicillin, and cefotiam. Nine patients also received
      intravenous steroids. Signs and symptoms of supraglottitis resolved within 10
      days in every case. No patient required airway intervention. Acute supraglottitis
      manifested more severe clinical symptoms than acute laryngitis. the local
      inflammatory findings of this disease were different from those of acute
      laryngitis and epiglottitis. therefore, we propose that acute supraglottitis is a
      special form of acute laryngitis.

PMID- 9184031
TI  - [Detection of human papilloma virus DNA and expression of p53 protein in patients
      with head and neck cancer].
AB  - We investigated the p53 expression and the presence of HPV DNA in 90 patients
      with squamous cell carcinomas (SCCs) of the head and neck and the relation to
      clinicopathological parameters and patients' prognosis. Immunohistochemical
      analysis of p53 protein was conducted by using monoclonal anti-p53 antibody,
      clone 1801 and clone 240. The relationship between the overexpression of p53 and
      the duration of survival of patients was analyzed. The polymerase chain reaction
      (PCR) was carried out with consensus primers capable of detecting HPV16, 18, 31,
      33, 52b and 58. In situ hybridization was performed in the mesopharyngeal
      carcinoma to confirm the presence of HPV genomes in cancer cells with a wide
      spectrum cDNA probe capable of detecting HPV6, 11, 16, 18, 30, 31, 33, 35, 45,
      51, 52. Forty-five tissue samples (50%) were immunohistochemically positive for
      p53. T-category, N-category, primary site of tumor, clinical stage and tumor
      differentiation did not correlate with p53 expression. Our finding that p53
      overexpression occurred in 50% of head and neck tumor samples is similar to the
      frequency of p53 overexpression reported for both lung and esophageal cancer. The
      common risk factor is the same in these neoplasms, and therefore it is not
      surprising to find a similar percentage of p53 overexpression. The prevalence of
      metastasis was higher in the patients with p53-positive staining than in those
      with p53-negative staining (p < 0.10). Analysis of cumulative survival rates of
      patients by the Kaplan-Meier method showed a close correlation between p53
      expression and survival time. The survival differences according to p53
      immunostaining were significant (p 0.05). Our results indicate that p53
      immunohistochemical evaluation may be useful as one of the new prognostic
      parameters in head and neck cancer patients. The HPV genomes were detected in 9
      of 90 patients (10.0%); 8 of 9 patients with mesopharyngeal cancer and one with
      maxillary cancer, namely, 29.6% of mesopharyngeal cancers and 6.7% of maxillary
      cancer contained HPV DNA sequences. Seven of 8 patients had SCCs of tonsil
      origin. Almost all of the HPV infections in our study occurred in patients with
      mesopharyngeal cancer, and it has been suggested that this anatomic subsite may
      be more frequently infected by HPV than other sites within the head and neck
      region. Among the 27 patients with mesopharyngeal cancer, HPV DNA-positive
      patients experienced a higher incidence of complete remission than HPV DNA
      negative patients (87.5% vs. 26.3%, p < 0.05).

PMID- 9184033
TI  - UVb-induced toxicity of PAHs: effects of substituents and heteroatom
      substitution.

PMID- 9184032
TI  - Migration and health-the international perspective.
AB  - Mass movement of people is not a new phenomenon. There are significant
      differences, however, between contemporary migration and that of yesterday.
      Modern communication and transportation makes it possible for people and their
      health problems to travel further and more quickly than ever before. The Plan of
      Action produced by the 1994 International Conference on Population in Cairo
      estimates that there are 125 million migrants world-wide. The cause of concern is
      not only linked to the numbers, but also to the new patterns and categories of
      migrants that give the strong feeling that the problem is getting out of control.
      This presents a challenge which urgently asks for response and action on various
      levels including health and social services. European states started to develop
      policies that would link immigration to health care policies. "Health for All"
      strategies, only towards the end of the 1980s, if at all. There are six areas,
      where health policies and programmes explicitly should take the needs of the
      immigrants into consideration: (1) communication and understanding, (2) control
      of infectious diseases, (3) mother and child care, (4) occupational health, (5)
      violence and (6) health indicators among migrants. To improve the health status
      of migrant families immigrant receiving countries need to put ethnic policies
      high on the public health agenda, they need to provide adequate health services
      to immigrants and there is a crucial need for training and preparing health
      professionals to understanding perspectives that differ from their own ethnic
      orientation, and to provide adequate and effective responses.

PMID- 9184035
TI  - Intestinal fish parasites as heavy metal bioindicators: a comparison between
      Acanthocephalus lucii (Palaeacanthocephala) and the zebra mussel, Dreissena
      polymorpha.

PMID- 9184036
TI  - Coelomic fluid lysozyme activity induction in the polychaete Eurythoe complanata
      as a biomarker of heavy metal toxicity.

PMID- 9184037
TI  - Closed-ampule digestion procedure for the determination of mercury in soil and
      tissue using cold vapor atomic fluorescence spectrometry.

PMID- 9184038
TI  - Blue-green alga Microcystis aeruginosa Kutz. in natural medium.

PMID- 9184039
TI  - Combined non-invasive cell isolation and neutral-red retention assay for
      measuring the effects of copper on the lumbricid Aporrectodea rosea (Savigny).

PMID- 9184040
TI  - Factors affecting the fate of urea peroxide added to soil.

PMID- 9184041
TI  - 14C-Residues of trifluralin in a soil and their uptake by carrots.

PMID- 9184042
TI  - Sorption of carbaryl (1-napthyl N-methyl carbamate) by soil.

PMID- 9184044
TI  - Elevated PCB contamination of coastal plants near Polynyas in the High Arctic.

PMID- 9184043
TI  - Studies on degradation of 14C-nitrofen in soils under moist and flooded
      conditions using a continuous flow system in the laboratory.

PMID- 9184045
TI  - Formation of polychlorinated biphenyls from the pyrolysis of
      hexachlorocyclohexane in the presence of Fe2O3.

PMID- 9184046
TI  - Levels of PCDDs and PCDFs in the bleached pulp from Chinese pulp and paper
      industry.

PMID- 9184047
TI  - Determination of lead and cadmium content in the rice consumed in Maracaibo,
      Venezuela.

PMID- 9184048
TI  - Occurrence of methylmercury in Lake Valencia, Venezuela.

PMID- 9184049
TI  - Polychlorinated biphenyls and organochlorine pesticides in the freshwater mussel
      Hyridella menziesi from the Waikato River, New Zealand.

PMID- 9184050
TI  - Heavy metals and acid-volatile sulfides in sediments of the Tijuana Estuary.

PMID- 9184051
TI  - Effects of chelation on the bioconcentraton of cadmium and copper by carp
      (Cyprinus carpio L.).

PMID- 9184052
TI  - Aluminum toxicity and nutrient utilization in the mycorrhizal fungus Hebeloma
      mesophacus.

PMID- 9184053
TI  - Effect of cadmium on antioxidant enzyme activities and lipid peroxidation in a
      freshwater field crab, Barytelphusa guerini.

PMID- 9184054
TI  - Effect of sediment from two sulphite-bleaching paper mills on winter flounder
      (Pleuronectes americanus) following chronic exposure.

PMID- 9184055
TI  - Effect of a polychlorinated biphenyl metabolite on early life stage survival of
      two species of trout.

PMID- 9184056
TI  - Protective effects of GSH, alpha-tocopherol, and selenium on lipid-peroxidation
      in liver and kidney of copper fed rats.

PMID- 9184057
TI  - Chemotaxis of mouse peritoneal macrophages following exposure to lead.

PMID- 9184058
TI  - Cadmium inhibits the in vitro conversion of thyroxine to triiodothyronine in rat
      brown adipose tissue.

PMID- 9184069
TI  - Direct role of the carboxy-terminal cell-binding domain of fibronectin in neural
      crest cell motility.
AB  - We have analyzed the interaction of neural crest cells with fragments of
      fibronectin corresponding to the different spliced variants of the COOH-terminal
      cell-binding domain (COOH-ter CBD). We have shown that this domain can support
      cell adhesion and migration and that both the IIICS and HepII regions are
      involved in these events. The rate of locomotion is high, although undirectional,
      compared to that of whole fibronectin. Interactions with the COOH-ter CBD are
      controlled by alpha4beta1 and maybe other beta1 integrins and cell-surface
      proteoglycans. These receptors act cooperatively to mediate attachment,
      spreading, and migration on fibronectin.

PMID- 9184070
TI  - Isolation and characterization of peroxisome-deficient Chinese hamster ovary cell
      mutants representing human complementation group III.
AB  - We made use of the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/UV) method and isolated
      peroxisome-deficient mutant cells. TKa cells, the wild-type Chinese hamster ovary
      (CHO) cells, CHO-K1, that had been stably transfected with cDNA encoding Pex2p
      (formerly peroxisome assembly factor-1, PAF-1) were used to avoid frequent
      isolation of the Z65-type, PEX2-defective mutants. P9OH/UV-resistant cell
      colonies were examined for the intracellular location of catalase, a peroxisomal
      matrix enzyme, by immunofluorescence microscopy and using anti-catalase antibody.
      As six mutant cell clones showed cytosolic catalase, there was likely to be a
      deficiency in peroxisome assembly. These mutants also showed the typical
      peroxisome assembly-defective phenotype, including significant decrease of
      dihydroxyacetonephosphate acyltransferase, the first step key enzyme in
      plasmalogen synthesis, and loss of resistance to 12-(1'-pyrene)dodecanoic acid/UV
      treatment. By transfection of Pex2p and Pex6p (formerly PAF-2) cDNAs and cell
      fusion analysis between the CHO cell mutants, two mutants, ZP104 and ZP109, were
      found to belong to a novel complementation group. Further complementation
      analysis using fibroblasts from patients with peroxisome biogenesis disorders
      revealed that the mutants belonged to human complementation group III. Taken
      together, ZP104 and ZP109 are in a newly identified fifth complementation group
      in CHO mutants reported to date and represent the human complementation group
      III.

PMID- 9184071
TI  - Cleavage of the nuclear matrix protein NuMA during apoptosis.
AB  - NuMA is a component of the nuclear matrix which may play a structural role in the
      architecture of the interphase nucleus. During apoptosis NuMA is redistributed
      within the nucleus and is proteolysed from a 238-kDa form to a 180- to 200-kDa
      form. Here we show that the cleavage site leading to the stable fragment occurs
      between residues 1701 and 1725. Both the changes in morphology associated with
      apoptosis and the cleavage of NuMA were retarded by treatment with TPCK but not
      by treatment by other protease inhibitors including ICE inhibitor II.

PMID- 9184072
TI  - Endogenous fibronectin of blood polymorphonuclear leukocytes: immunochemical
      characterization and subcellular localization.
AB  - Fibronectin, a large dimeric glycoprotein synthesized and secreted by several
      cell types, mediates cell adherence to surfaces. In infections and inflammatory
      responses, blood polymorphonuclear leukocytes (PMNs) adhere to cells and matrix
      proteins during extravasation and accumulation at inflammatory sites. The
      presence of fibronectin in blood PMNs has been poorly studied, and the
      characteristics and subcellular localization of this endogenous adhesive molecule
      are practically unknown. By immunofluorescence flow cytometry, purified rabbit
      antibodies and a monoclonal antibody to plasma fibronectin reacted with isolated
      blood PMNs, only after permeabilization of the cells. By Western blot analysis,
      the antibodies recognized, under reducing conditions, a protein with an apparent
      molecular mass of 230 kDa in the cell lysate. Eleven monoclonal antibodies to
      common frame fibronectin epitopes, including the RGD-containing cell-binding
      domain, also reacted with PMN fibronectin by Western blotting. In contrast, two
      antibodies to ED-A, the alternatively spliced region characteristic of "cellular"
      fibronectin, were unreactive, but recognized platelet fibronectin. On average, 1
      million PMNs contained 6.8 ng +/- 1.4 (SD) of fibronectin, as measured by
      sandwich ELISA. Immunogold labeling and electron microscopy studies indicated
      localization of most fibronectin in PMN granules. Moreover, double
      immunofluorescence and digital image analysis demonstrated colocalization of
      fibronectin with lactoferrin, a marker of specific (secondary) granules. The
      results indicate that blood PMNs contain approximately 8000 molecules per cell of
      intact ED-A-negative fibronectin localized mainly in their specific granules.

PMID- 9184073
TI  - Endogenous fibronectin of blood polymorphonuclear leukocytes: stimulus-induced
      secretion and proteolysis by cell surface-bound elastase.
AB  - In an accompanying study, we described the presence of intact fibronectin, a
      large adhesive molecule, in the specific granules of blood PMNs. Secretion of
      fibronectin by blood PMNs is poorly understood, and the fate of this fibronectin
      is practically unknown. In the present study we demonstrate that nanomolar
      concentrations of phorbol ester or the chemoattractants fMLP, PAF, and LTB4
      induce fibronectin secretion from blood PMNs. Phorbol ester induced secretion of
      approximately 85% of the total fibronectin content, as well as expression of
      small amounts on the cell surface of the activated PMNs. Secreted fibronectin was
      proteolytically cleaved and, after 20 min, four major fragments of 150, 120, 90,
      and 80 kDa containing a midchain epitope were identified by Western blot
      analysis. Kinetic studies indicated that fibronectin was rapidly secreted as an
      intact molecule and that proteolysis started within minutes and proceeded for at
      least 1 h. If cells were removed after 5 min TPA treatment, no further
      proteolysis of the secreted fibronectin was observed, indicating participation of
      cell-bound proteinases. From a cocktail of proteinase inhibitors, PMSF was the
      most active in suppressing fibronectin proteolysis. Studies with specific
      peptidyl inhibitors of human leukocyte elastase and cathepsin G, major serine
      proteinases of PMNs, demonstrated some inhibition with the cathepsin G inhibitor,
      while the human leukocyte elastase inhibitor almost completely abolished
      fibronectin proteolysis. A monoclonal antibody to the elastase had a similar
      effect. The results indicate that intact fibronectin is a secretory product of
      blood PMNs and that this endogenous adhesive molecule is within minutes
      extracellularly processed by cell surface-bound elastase.

PMID- 9184074
TI  - Sequential operation of ceramide synthesis and ICE cascade in CPT-11-initiated
      apoptotic death signaling.
AB  - The chemotherapeutic agent CPT-11 induced apoptotic cell death in mouse
      fibroblast 4B1 cells. To examine the intracellular apoptotic death signal
      initiated by CPT-11, ceramide synthesis and the ICE cascade were analyzed. CPT-11
      initiated cytolytic activity was prevented by both caspase inhibitors YVAD-CHO
      and DEVD-CHO, or ceramide synthesis inhibitor fumonisin B1, and accelerated by
      sphingomyelin, suggesting the direct involvement of ceramide synthesis and the
      interleukin 1-beta converting enzyme (ICE) cascade. In addition, apoptosis was
      induced by both native and synthesized ceramide and prevented by YVAD-CHO and
      DEVD-CHO, suggesting the possible involvement of ceramide in ICE cascade
      operation. To directly demonstrate whether ceramide synthesis operates the ICE
      cascade, proteolytic activity of ICE- or CPP32-like proteinase was analyzed. ICE
      like proteinase activity was prevented by fumonisin B1 and YVAD-CHO, but not by
      DEVD-CHO. In contrast, fumonisin B1, YVAD-CHO, and DEVD-CHO all prevented CPP32
      like proteinase activity. These results suggest that ceramide synthesis acts as a
      dominant regulator in CPT-11-initiated death signaling and sequentially operates
      the ICE cascade.

PMID- 9184075
TI  - Involvement of cytoplasmic serine proteinase and CPP32 subfamily in the molecular
      machinery of caspase 3 activation during Fas-mediated apoptosis.
AB  - On stimulation by the Fas ligand, the death receptor, Fas, initiates a signal
      leading to apoptotic cell death. Fas plays an important role in physiological
      cell death and is closely involved in various disease states. Recent
      investigations have shown that caspase 3 plays a dominant role in the process of
      Fas-mediated apoptosis. In the present study, we investigated the molecular
      machinery of caspase 3 activation in Fas-mediated apoptosis. The results showed
      that Fas-mediated apoptosis was accompanied by caspase 3 activation, and both Fas
      mediated apoptosis and caspase 3 activation were prevented by a serine proteinase
      inhibitor. In addition, the serine proteinase inhibitor also prevented the
      caspase 3 activation in cytoplasts, and the specific activation of
      serineproteinase was encountered in only cytoplasmic proteins. These results
      suggest that cytoplasmic serineproteinase plays an important role in caspase 3
      activation. Interestingly, caspase 3 was cleaved at p3 site immediately after Fas
      Ab stimulation, and the cleavage at p17 site became detectable later. We also
      found that among tested proteinases only Staphylococcus aureus V8
      serineproteinase initiated caspase 3 activation and specifically cleaved at p3
      site. These results strongly suggest that a cytoplasmic S. aureus V8-like serine
      proteinase is closely involved in caspase 3 activation.

PMID- 9184076
TI  - The interaction of sperm cells with exogenous DNA: a role of CD4 and major
      histocompatibility complex class II molecules.
AB  - Mouse epidydimal sperm cells have the spontaneous ability to take up exogenous
      DNA, a part of which is further internalized into nuclei. We report here that
      sperm cells from MHC class II knockout mice have a reduced ability to bind DNA
      compared to sperm cells from wild-type animals. Spermatozoa from CD4 knockout
      mice are instead fully capable of binding exogenous DNA, yet lose the ability to
      further internalize it. MHC class II expression was not detected on sperm heads
      using monoclonal antibodies. In contrast, CD4 molecules were found on sperm heads
      by both immunofluorescence and Western blot analysis. Moreover, we show that
      nuclear internalization of exogenous DNA was prevented in wild-type sperm cells
      preincubated with anti-CD4 mAbs. These results support the conclusion that CD4
      and MHC class II molecules play distinct roles in the process of sperm/DNA
      interaction: though not present in mature sperm cells, MHC class II expression
      appears to be required during spermatogenesis to produce sperm cells capable of
      taking up foreign DNA, while CD4 molecules present on sperm cells mediate the
      nuclear internalization of sperm-bound DNA.

PMID- 9184078
TI  - The role of LFA-1 (CD11a/CD18) cytoplasmic domains in binding to intercellular
      adhesion molecule-1 (CD54) and in postreceptor cell spreading.
AB  - We have investigated the role of the cytoplasmic domains of LFA-1 in binding to
      ICAM-1 and in postadhesion events. Various truncated and chimeric forms of LFA-1
      alpha (CD11a) and beta (CD18) chains were generated and transfected into murine
      fibroblast TNR-2 cells. Transfected fibroblasts expressing wild-type LFA-1
      adhered only weakly to ICAM-1 immobilized on plastic, and phorbol ester
      pretreatment enhanced this adhesion significantly. In contrast, transfected cells
      expressing LFA-1 lacking both the alpha and the beta cytoplasmic domains, the
      beta cytoplasmic domain alone, or GPI-anchored LFA-1 adhered to immobilized ICAM
      1 without prior activation. Truncation of the alpha cytoplasmic domain alone
      resulted in much reduced cell adhesion which could be only weakly upregulated by
      PMA. The presence of manganese dramatically enhanced the binding to ICAM-1 of LFA
      1 lacking the alpha cytoplasmic domain or both cytoplasmic domains, whereas it
      had relatively little effect on wild-type LFA-1 or the mutant lacking the beta
      cytoplasmic domain. Soluble LFA-1, generated by phosphatidylinositol-specific
      phospholipase-C treatment of GPI-anchored LFA-1, was capable of binding ICAM-1+
      cells. Although doubly truncated or GPI-anchored LFA-1 mediated cell adhesion to
      immobilized ICAM-1, cells expressing these mutants, as well as those expressing
      individual alpha and beta chain truncations, failed to spread out following this
      adhesion, whereas the wild-type transfectants did so readily. Manganese had no
      effect on cell spreading. Fluorescent staining of these cells indicated no
      significant variation in the distribution of LFA-1 on the cell surface. From
      these results we conclude that (1) cells expressing LFA-1 lacking both the alpha
      and the beta cytoplasmic domains adhere to ICAM-1 without prior stimulation,
      indicating the importance of LFA-1 cytoplasmic domains in inside-out signaling,
      (2) truncation of the alpha cytoplasmic domain alone inhibits cell adhesion by
      making LFA-1 nonresponsive to inside-out signaling, and (3) both cytoplasmic
      domains are required for cell spreading following adhesion to immobilized ICAM-1.

PMID- 9184077
TI  - Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities,
      metabolism, and localization during development.
AB  - cyr61 and fisp12 are homologous immediate-early genes that are transcriptionally
      activated upon growth factor stimulation in fibroblasts. Their gene products
      belong to an emerging family of secreted proteins with a high degree of sequence
      homology, including conservation of all 38 cysteine residues in their secreted
      portions. We have recently shown that Cyr61 is an extracellular matrix (ECM)
      signaling molecule that promotes cell proliferation, migration, and adhesion. We
      describe herein the first purification of the Fisp12 protein and we compare the
      activities of purified Cyr61 and Fisp12, their metabolism, targeting, and their
      localization during development. Although Fisp12 is the mouse homolog of the
      human connective tissue growth factor (CTGF), it has no detectable mitogenic
      activity by itself. Rather, Fisp12 enhances fibroblast growth factor-induced DNA
      synthesis. The activities of Fisp12 and Cyr61 are nearly indistinguishable in
      three cell types tested: fibroblasts, endothelial, and epithelial cells. Both
      proteins are found in the ECM, although Cyr61 associates with the ECM more
      strongly and binds heparin with higher affinity. Fisp12, but not Cyr61, is also
      found in the culture medium, suggesting that Fisp12 might be able to act at a
      distance from its site of secretion, whereas Cyr61 might act more locally. Both
      secreted proteins are internalized and degraded through the lysosomal pathway,
      suggesting interaction with cell surface receptors. Both Cyr61 and Fisp12 are
      found in the placenta and the circulatory system as detected by
      immunohistochemistry, whereas Cyr61, but not Fisp12, is found in the skeletal and
      nervous systems. Fisp12, but not Cyr61, is found in secretory organs. Taken
      together, we propose that Cyr61 and Fisp12 are both signaling cell adhesion
      molecules that have similar or overlapping activities, and their differential
      sites of localization and targeting may dictate specificity in their biological
      roles.

PMID- 9184079
TI  - Multiple attachment mechanisms of corneal epithelial cells to a polymer--cells
      can attach in the absence of exogenous adhesion proteins through a mechanism that
      requires microtubules.
AB  - The initial adhesion of epithelial cells is recognized as a critical determinant
      in the epithelialization of a polymer. Previously, the attachment of a variety of
      cell types to a polymer has been shown to be mediated by fibronectin and/or
      vitronectin that adsorb onto the polymer surface from the serum used to
      supplement the culture medium. Such an attachment reaction, dependent upon
      exogenous cell-adhesive proteins, is likely to involve the actin cytoskeleton and
      integrin receptors on the cell surface. In the current study, we have examined
      the attachment of recently isolated corneal epithelial cells to tissue culture
      polystyrene in the absence of such exogenous cell-adhesive proteins. Under these
      circumstances, there is an alternative mechanism of attachment operative between
      corneal epithelial cells and the polymer surface which is essentially independent
      of the adsorption of serum-derived fibronectin and vitronectin. This is an
      unusual phenomenon not previously observed with other normal cell types. The
      presence of cycloheximide inhibited this alternative attachment mechanism in
      corneal epithelial cells, indicating the role of newly synthesized proteins in
      this reaction. Additionally, we found that cell attachment to the polymer surface
      in the absence of cell-adhesive proteins was substantially inhibited by the
      presence of demecolcine, but not by cytochalasin B, thereby demonstrating the
      involvement of microtubules rather than actin microfilaments in this reaction. In
      the presence of serum-derived fibronectin and vitronectin, the attachment of
      corneal epithelial cells to a polymer may involve dual attachment mechanisms.

PMID- 9184080
TI  - Prosome cytodistribution relative to desmin and actin filaments in dividing C2.7
      myoblasts and during myotube formation in vitro.
AB  - Prosomes constitute the multicatalytic proteinase (MCP) core of the 26S
      proteasomes, but were first observed as subcomplexes of untranslated mRNP; this
      suggests that they play a putative role in the control of protein biosynthesis in
      addition to their catabolic enzymatic function. In previous investigations it was
      shown that some prosomes colocalize with the intermediate filaments (IF) of the
      cytoskeleton, of the cytokeratin type in epithelial cells, and of the vimentin
      type in fibroblasts. Studies on adult rat muscle carried out with prosome
      specific monoclonal antibodies (p-mAbs) have shown, surprisingly, that specific
      types of prosomes predominantly occupy a particular zone in between the M and the
      Z lines of the sarcomeric structure. The data presented here show that the
      subunit composition of prosomes changes when the dividing C2.7 myoblasts fuse
      into myotubes. We show furthermore that, in dividing C2.7 myoblasts, prosomes
      colocalize with the desmin network as well as with that of actin, in a
      distribution that changes with the subunit pattern of the prosomes investigated
      by individual p-mAbs. Surprisingly, when myogenic fusion is induced, specific
      types of prosomes move first to the nuclei; later on, they reappear in the
      cytoplasm. There, superimposing initially onto the reorganizing desmin filaments
      that run from one pole of the prefusion myoblast to the other, prosomes gradually
      colocalize with the actin fibers in the fusing myotubes, finally forming a "pearl
      on a string" pattern. These results are discussed in relation to parallel
      observations of prosome distribution between the actin and IF networks not only
      in epithelial cells but also in fusing muscle satellite cells, which made it
      possible to monitor the complete buildup of the sarcomeric structure.

PMID- 9184081
TI  - Modulation in cell cycle and cyclin B1 expression in irradiated HeLa cells and
      normal human skin fibroblasts treated with staurosporine and caffeine.
AB  - The comparative effects of staurosporine or caffeine on G2-phase arrest and
      cyclin B1 expression in human skin fibroblasts (HSF) and transformed HeLa cells
      following gamma-irradiation were examined by flow cytometry. Contrary to some
      earlier reports with HeLa cells, the arrest in G2 after irradiation was
      accompanied by an increase in cyclin B1 levels in both asynchronous and
      synchronized HeLa cells irradiated in early S phase. Caffeine and staurosporine
      were equally effective in attenuating both the radiation-induced increase in
      cyclin B1 expression and the prolongation of G2 in synchronous and asynchronous
      HeLa cell populations. Staurosporine treatment was less effective in down
      regulating cyclin B1 expression in asynchronous HeLa cells at earlier time points
      following irradiation when compared to caffeine-treated cells. In synchronized
      HeLa cells, down-regulation of an irradiation-induced increase in cyclin B1
      expression was similar to either staurosporine or caffeine treatments, with
      caffeine being more effective at later time points. An increase in cyclin B1
      expression was also observed in irradiated HSF cells (synchronous and
      asynchronous), which decreased when the cells were treated with staurosporine or
      caffeine. However, staurosporine was ineffective in attenuating the radiation
      induced prolongation of G2 in synchronous and asynchronous HSF cells, whereas
      treatment of irradiated synchronous or asynchronous HSF cells with caffeine
      significantly reduced the prolongation of G2. These results suggest that both
      staurosporine and caffeine treatments act on different pathways of cell cycle
      control in normal and transformed cells, in terms of attenuation of G2 block and
      diminution of elevated levels of cyclin B1 expression, in response to radiation.

PMID- 9184083
TI  - Early ultraviolet B-induced G1 arrest and suppression of the malignant phenotype
      by wild-type p53 in human squamous cell carcinoma cells.
AB  - Wild-type p53 (wt-p53) negatively controls cell cycle progression after cellular
      stress mediating either a temporary growth arrest or apoptosis, depending on the
      cell type and nature of the cellular stress. The aberrant proliferation which is
      characteristic of tumor cells may be suppressed by exogenous wt-p53 and appears
      to depend strongly on the level of reexpression. We performed retroviral-mediated
      gene transfer of wt-p53 into a human squamous cell carcinoma cell line from the
      head and neck region (A253 cell line) lacking endogenous p53. This allowed us to
      study the effect of wt-p53 on the malignant phenotype and on the response to the
      DNA damaging agent ultraviolet B (UVB). Restoration of wt-p53 in malignant
      keratinocytes suppressed tumorigenicity in nude mice although p53-reconstituted
      cells eventually formed small tumors with long latency. Cells derived from these
      tumors showed reduced expression of wt-p53. Exogenous wt-p53 increased baseline
      mRNA expression of the small proline rich proteins 1 and 2, consistent with a
      prodifferentiating effect. After exposure to a biological UVB dose, only p53
      positive A253 cells underwent an early and transient G1 arrest. Both p53-positive
      and -negative A253 cells displayed a late G2 delay/arrest. We conclude that
      reexpression of wt-p53 in squamous cell carcinoma A253 cells decreases their
      malignant phenotype and reestablishes a G1 checkpoint after UVB.

PMID- 9184082
TI  - Fatty acid alteration and the lateral diffusion of lipids in the plasma membrane
      of keratinocytes.
AB  - The fluorescent probe diI was used to study the lateral mobility of lipids in in
      vitro strains of living adult human keratinocytes grown in four different media.
      One medium was essential fatty acid deficient (EFAD) and low in calcium ion, a
      medium known to yield cells that proliferate rapidly and contain lipid with
      extremely low levels of essential fatty acids. Two other media were supplemented
      with essential fatty acids (FAS), media that are known to result in cells that
      grow more slowly and have normalized fatty acid proportions. A fourth medium
      consisted of 1 microM all-trans-retinoic acid added to the fatty acid
      supplemented medium (FAS-RA), a medium known to produce cells that are highly
      proliferative, with a growth rate greater than that of the FAS strains and
      similar to that of the EFAD strains. The keratinocytes grown in these four media
      were studied using the fluorescence recovery after photobleaching (FRAP)
      technique to determine the lateral diffusion rate of diI in the plasma membranes.
      Our results showed a positive correlation between growth rate and diffusion
      coefficient (D): the diffusion coefficient of diI was higher in the EFAD or FAS
      RA cells than in the FAS cells. The measurement of D among the FAS cells fell
      into two groups. One group was similar to the single group seen in the EFAD
      cells, but the other group was composed of much lower D values. The other FRAP
      parameters (mobile fraction and bleach depth) were larger in the "slow" group
      than in the "fast" group. This trend of negative correlation between these
      parameters and D was also found within the fast group. These results are
      interpreted in terms of possible changes in membrane structure or morphology that
      might be indirectly associated with the fatty acid alterations, including the
      possible presence of areas in senescing keratinocytes where plasma membranes
      collapse to form an interacting system of lipid bilayers.

PMID- 9184084
TI  - Cell density regulates crypticity of GM3 ganglioside on human glioma cells.
AB  - Human glioma cell line KG-1C contains GM3 ganglioside as its sole glycolipid. The
      degree of M2590 antibody binding to GM3 was found to be regulated by the cell
      density; the percentage of positive cells in FACS analysis decreased from
      approximately 20% to close to none as the cells increased their density from
      sparse to confluent. The contents of GM3 with different cell densities were
      consistent, being more than 0.4 micromol/g of the cellular weight, which was high
      enough to be recognized by the antibody. Trypsin treatment of the cells did not
      increase antibody reactivity. The extracted GM3 retained its antigenicity, being
      intensely stained with M2590 on a TLC plate; there was no change in
      chromatographic mobility either, indicating no modification of its chemical
      structure. The fluorescent microscope disclosed scattered dot-like staining of
      GM3, particularly at the periphery of the cells. We were able to expose cryptic
      GM3 fully within 12 h by dispersion of the cells to a sparse density. Surface
      labeling of GM3 with the use of limited sodium periodate oxidation of sialylated
      residue equally labeled GM3 either from the confluent cells or the sparse cells.
      Disassembly of actin filaments with cytochalasin B (10 microM) partially exposed
      cryptic GM3 of confluent cells, indicating reversibility of the crypticity. All
      together, the results indicate that cryptic GM3 actually exists on the cell
      surface, hidden from the surface not by other molecules but by other mechanisms
      associated with the cellular architecture. We are beginning to explore the
      possibility of selective localization of GM3 in small caves or folds of the cell
      membrane produced upon cell-to-cell contact.

PMID- 9184085
TI  - Reassembly of functional nucleoli following in situ unraveling by low-ionic
      strength treatment of cultured mammalian cells.
AB  - In order to determine the most persistent components of the nucleolus that might
      serve as "core" nucleolar elements, we studied the reactivity of nucleoli in
      living mammalian cells subjected to hypotonic buffer saline followed by the
      incubation of the cells in an isotonic medium. To document as precisely as
      possible the fine structural changes which occurred, the cells were examined by
      video-enhanced optical microscopy, fluorescence confocal laser scanning
      microscopy, and electron microscopy combined with cytochemistry. Light
      microscopic autoradiography was used to demonstrate the transcriptional
      characteristics of the reassembled nucleoli. It was shown that all the major
      compartments of the intact nucleolus could be substantially affected by reduction
      of the osmolarity of the environmental media. The dynamic events of the nucleolar
      unraveling in low-salt buffers occurred in the following order: dispersion of the
      nucleolar pars granulosa, disassociation of the fibrillar complexes into discrete
      fibrillar centers (FCs) and the dense fibrillar component (DFC), and the almost
      complete unraveling of the DFC and FCs. At the terminal stages of nucleolar
      dispersion, the nuclear interior was mainly composed of a loose filamentous
      meshwork, and none of the typically discerned nucleolar constituents was
      recognized. Nevertheless, when hypotonically treated cells were returned to
      isotonic conditions, the nucleolar bodies rapidly began to reassemble. Within 1-2
      h of cell incubation under isotonicity, the nucleoli not only became clearly
      visible, but also reconstituted to their initial size, shape, and position within
      the nucleus. The ultrastructure and functional activity of the reassembled
      nucleoli were also found to be fully comparable to those of the untreated
      controls. These data indicate that the architectural composition of the
      interphase nucleolus is strictly controlled by the cell. As far as could be
      determined, none of the usual substructures of the intact nucleolus that could be
      substituted by complete reassembly of the nucleolar bodies in normotonic
      conditions, including FCs and the DFC, remained clearly preserved in the terminal
      stage of nucleolar unraveling. We concluded that the integrity of the nucleolus
      was mainly preserved by the nuclear or nucleolar matrix system rather than by any
      other nucleolar structural domains.

PMID- 9184086
TI  - Binding of fluorescence- and gold-labeled oligodeoxyribonucleotides to
      cytoplasmic intermediate filaments in epithelial and fibroblast cells.
AB  - Previously, in vitro experiments have demonstrated the capacity of intermediate
      filaments (IFs) to associate with polyanionic compounds, including nucleic acids.
      To prove that this activity is also shown by IFs in quasi-intact cells, digitonin
      permeabilized epithelial PtK2 and mouse fibroblast cells were treated with FITC
      labeled, single-stranded oligodeoxyribonucleotides and analyzed, after indirect
      decoration of their IF systems with TRITC-conjugated antibodies, by fluorescence
      microscopy. While cytokeratin IFs exhibited a strong affinity for and exact
      codistribution with oligo(dG)25, vimentin IFs were less active in binding this
      oligonucleotide. Other oligonucleotides, like oligo(dT)25, oligo[d(GT)12G] and
      oligo[d(G3T2A)4G], were bound to IFs with lower efficiency. In general, the
      introduction of dA residues into oligo(dG)n or oligo(dGT)n tracts reduced the IF
      binding potential of the nucleic acids. This, however, increased significantly
      upon reduction of the ionic strength to half physiological, indicating a strong
      electrostatic binding component. The binding reaction was often obscured by
      simultaneous association of the oligonucleotides with cellular membranes mostly
      in the perinuclear region, an activity that was largely abolished by prior cell
      extraction with nonionic detergent. Strongly IF-binding oligonucleotides also
      disassembled microtubules, presumably via their interaction with microtubule
      associated proteins, but left microfilaments intact. In PtK2 cells, oligo(dG)25
      loaded IFs were frequently seen coaligned with microfilaments and to cross-bridge
      stress fibers with the formation of rope ladder-like configurations. Employing
      microinjection and confocal laser scanning microscopy, association of IFs with
      oligonucleotides could also be visualized in intact cells. In accord with these
      fluorescence microscopic data, transmission electron microscopy of permeabilized
      cells treated with gold-conjugated oligonucleotides revealed decoration of IFs
      and membrane systems with gold particles, whereby in PtK2 cells these structures
      showed a distinctly heavier labeling than in fibroblasts. These results
      demonstrate that in animal cells IFs are able to bind nucleic acids and, very
      likely, also nucleoprotein particles and suggest that this capacity is exploited
      by the cells for transient storage and, in cooperation with microtubules and
      microfilaments, controlled transport of such material in the cytoplasm.

PMID- 9184087
TI  - 2-chloroadenosine stimulates granule exocytosis from mouse natural killer cells:
      evidence for signal transduction through a novel extracellular receptor.
AB  - The effect of 2-chloroadenosine (2CA), an adenosine receptor agonist, on the
      activation status of mouse natural killer (NK) cells was determined. Splenic
      lymphocytes incubated with 2CA exocytosed an NK cell-associated granzyme with N
      alpha-CBZ-L-lysine thiobenzyl ester (BLT) esterase activity in a dose- and time
      dependent manner. Selective depletion of NK cells by anti-asialoGM1 antibody plus
      complement pretreatment confirmed that NK cells were the source of the BLT
      esterase activity. 2CA-induced granule exocytosis was not reduced in the presence
      of the nucleoside uptake blockers NBTI, dilazep, or dipyridamole, indicating the
      involvement of an extracellular receptor. However, adenosine or other A1, A2, or
      A3 cell-surface adenosine receptor agonists failed to trigger the exocytotic
      process. Furthermore, the nonselective adenosine receptor antagonist
      theophylline, as well as the selective A1 receptor antagonist DPCPX and the
      selective A2 receptor antagonist DMPX, did not interfere with 2CA-induced BLT
      esterase secretion. These data suggest that 2CA acts on NK cells via a novel (non
      A1/A2/A3) cell-surface receptor. Genistein, a protein tyrosine kinase inhibitor,
      and calphostin C, a protein kinase C inhibitor, both interfered with 2CA-induced
      granule exocytosis. Pertussis toxin, an ADP-ribosylating toxin to which certain
      GTP-binding proteins are sensitive, also inhibited 2CA-stimulated BLT esterase
      release. In addition, 2CA-induced granule exocytosis was reduced in the presence
      of cyclosporin A, an inhibitor of Ca(2+)-dependent signaling pathways, and the
      Ca(2+)-chelating agent EGTA. We conclude that 2CA, acting through a novel
      extracellular receptor on mouse NK cells, triggers granule exocytosis via a
      Ca(2+)-dependent signal transduction pathway that is coupled to GTP-binding
      proteins and involves protein tyrosine kinase and protein kinase C activation.

PMID- 9184088
TI  - FGF2-stimulated release of endogenous FGF1 is associated with reduced apoptosis
      in retinal pigmented epithelial cells.
AB  - Both inhibition of endogenous fibroblast growth factor (FGF) synthesis on
      nondividing lens epithelial cells and inhibition of secreted FGF1 in confluent
      quiescent retinal pigmented epithelial (RPE) cells induce rapid cell apoptosis
      (Renaud et al., 1996, J. Biol. Chem., 271, 2801-2811). In addition several
      studies demonstrate that exogenous FGF2 can promote retinal cell survival in
      vitro and in vivo. To determine the possible relationship between exogenous FGF2,
      endogenous FGF1, and cell survival, we examined the protective effect of a single
      dose of exogenous FGF2 on long-term culture of quiescent RPE cells after serum
      withdrawal. After 4 days of culture, a dramatic and sustained upregulation of
      FGF1 protein expression occurs specifically in response to exogenous FGF2. After
      addition of FGF2 (20 ng/ml), RPE cells express fourfold more FGF1 after Day 7
      than after Day 1 of culture. This phenomenon is FGF2 dose-dependent. In contrast,
      neither serum nor FGF2 have an effect on total endogenous FGF2 expression. In
      addition, in response to exogenous FGF2, FGF1 is secreted in significant amounts
      into the extracellular medium at a rate comparable to FGF1 accumulation within
      the cell. Furthermore, in the absence of serum, significant increase in cell
      death occurs on Day 6 of culture, whereas addition of exogenous FGF2 induces a
      twofold decrease of RPE cell apoptosis. In the presence of exogenous FGF2,
      addition of a specific anti-FGF1 neutralizing antibody induces a rapid apoptosis
      of RPE cell cultures. Thus, we speculate that exogenous FGF2 may indirectly
      prolong cell survival by increasing synthesis and secretion of endogenous FGF1
      and that endogenous FGF1, directly in response to exogenous FGF2, may function as
      an autocrine trophic factor in RPE cells.

PMID- 9184089
TI  - Differential expression pattern of Rab-GDI isoforms during the parotid gland
      secretion cycle.
AB  - Rab GDP dissociation inhibitor (GDI) plays an important role in regulating the
      GDP/GTP cycle of small GTP binding proteins of the Rab family. It also regulates
      their association to membranes. The small family of Rab-GDI consists of several
      closely related isoforms, the functional differences between which are still
      unknown. Here we show that multiple GDI isoforms are expressed in rat parotid
      gland and that the individual GDI isoforms have a characteristic expression both
      at the RNA and at the protein level, during the parotid secretory cycle.
      GDIalpha, the major isoform in brain, is expressed throughout the secretory
      process and is equally distributed between cytoplasmic and membranous fractions.
      In contrast, an isoform related to, but different from GDIbeta is found
      predominantly in the cytoplasmic fraction and its expression is detected only
      after beta-adrenergic stimulation of the gland, at the end of the secretion
      phase, when exocytosis is already completed. The induction of such a GDI isoform
      at the beginning of the recovery stage correlates with the expression pattern of
      Rab1 and Rab5, but not Rab2 and Rab4. Our results suggest different functional
      roles for multiple GDI isoforms along the secretion and recovery phases in rat
      parotid gland.

PMID- 9184090
TI  - CP beta3, a novel isoform of an actin-binding protein, is a component of the
      cytoskeletal calyx of the mammalian sperm head.
AB  - In the mammalian sperm head, the nucleus is tightly associated with the calyx, a
      cell type-specific cytoskeletal structure. Previously, we have identified and
      characterized some basic proteins such as calicin and cylicins I and II as major
      calyx components of bovine and human spermatids and spermatozoa. Surprisingly we
      have now discovered another calyx constituent which by amino acid sequencing and
      cDNA cloning was recognized as a novel isoform of the widespread beta subunit of
      the heterodimeric actin-binding "capping protein" (CP). This polypeptide, CP
      beta3, of sperm calices, is identical with the beta2 subunit present in diverse
      somatic cell types, except that it shows an amino-terminal extension of 29 amino
      acids and its mRNA is detected only in testis and, albeit in trace amounts,
      brain. This CP beta3 mRNA contains the additional sequence, encoded by exon 1 of
      the gene, which is missing in beta2 mRNAs. Antibodies specific for the beta3
      amino-terminal addition have been used to identify the protein by immunoblotting
      and to localize it to the calyx structure by immunofluorescence microscopy. We
      conclude that in spermiogenesis the transcription of the gene encoding the beta1,
      beta2, and beta3 CP subunits is regulated specifically to include exon 1 and to
      give rise to the testis isoform CP beta3, which is integrated into the calyx
      structure of the forming sperm head. This surprising finding of an actin-binding
      protein isoform in an insoluble cytoskeletal structure is discussed in relation
      to the demonstrated roles of actin and certain actin-binding proteins, such as
      Limulus alpha-scruin, in spermiogenesis and spermatozoa.

PMID- 9184091
TI  - Inhibition of expression of PKC-alpha by antisense mRNA is associated with
      diminished cell growth and inhibition of amylase secretion by AR4-2J cells.
AB  - AR4-2J pancreatoma cells were stably transfected with an expression vector
      containing the cDNA for PKC-alpha in the antisense orientation. Transfectants
      designated antisense-alpha AA1, AA2, and AA3 exhibited marked reductions in PKC
      alpha expression and decrements in cell growth. The magnitude of the decrement in
      cell growth paralleled the reduction in PKC-alpha expression, i.e., AA3 > AA1 >
      AA2. The ability of dexamethasone to induce cell differentiation as assessed by a
      rise in cellular amylase levels was not markedly affected by the reduction in PKC
      alpha expression. Unstimulated amylase release was attenuated in AA1 cells and
      almost completely blocked in AA2 transfectants. The AA2 transfectant cell line
      failed to elicit a secretory response to caerulein, and the AA1 transfectant
      exhibited a lack of the secondary phase of stimulated amylase secretion. These
      findings demonstrate that PKC-alpha is involved in the mechanisms regulating
      growth and secretion in AR4-2J cells, but is not necessary for the induction of
      amylase stores following differentiation.

PMID- 9184092
TI  - Early sign language acquisition and the development of hand preference in young
      children.
AB  - Hand preference for signing and for nonsign actions was examined longitudinally
      in 24 young children (3 deaf, 21 hearing) with deaf parents. Most of these
      children showed a strong preference for their right hands in their sign
      production. This preference emerged early in their development, was relatively
      consistent over time, and predicted mature hand preference. Although most of the
      children also preferred to use their right hands in nonsign actions, their right
      hand preference for signing was much stronger. Hand preference scores for two
      types of nonsign actions, communicative gestures and object actions, were
      significantly correlated with those for signing. Hand preference also was linked
      to rate of motor development but not to sign language acquisition. These findings
      are discussed with regard to current conceptualizations about the
      interrelationships among language, motor processes, and laterality.

PMID- 9184093
TI  - Remediating production of tense morphology improves verb retrieval in chronic
      aphasia.
AB  - Production of tense markers in C-VIC, a computerized visual communication system,
      was utilized as a treatment for three patients with severe expressive aphasia.
      Patients practiced constructing C-VIC tense marked sentences and then producing
      English equivalents. After training, all patients demonstrated significant
      improvements in English verb retrieval and production of correct tense
      morphology. Generalization of morphological rules for past tense production was
      seen for regular, but not irregular verbs. These results support the LaPointe and
      Dell (1989) extension of the Garrett (1975, 1992) model specifying a search
      through so-called verb phrase notion stores as a process mediating transition
      from functional to positional levels, but also suggest an additional constraint
      on the output of the verb notion store search.

PMID- 9184094
TI  - Activation of the phonological lexicon for reading and object naming in deep
      dyslexia.
AB  - Poor oral reading in some cases of deep dyslexia could be due to difficulty in
      inhibiting the phonological lexical entries of words semantically related to the
      correct reading responses. If this is the case, then additional activation of the
      correct phonological entries should improve reading performance, whereas
      additional activation of competing entries should lead to errors. This should
      hold true for object naming as well as for reading, since both depend on a
      semantically mediated lexical route. These predictions were borne out with an
      "output" deep dyslexic patient, who made many semantic errors in both reading and
      naming. Providing phonetic cues (the initial portions of the correct responses)
      increased his reading and naming accuracy, and providing miscues (the initial
      portions of words related semantically to the correct responses) led to errors.
      Furthermore, when the patient was shown a printed word or pictured object and the
      examiner spoke a correct reading or naming response in isolation, the patient
      almost always accepted the response as correct, but he also judged that many
      semantically related foils were correct. Finally, a comparison of reading and
      naming errors suggested that "visual" errors may sometimes have a phonological
      basis.

PMID- 9184095
TI  - Are subjects' perceptual asymmetries on auditory and visual language tasks
      correlated?: a meta-analysis.
AB  - A number of studies have investigated the correlation between subjects'
      perceptual asymmetries on auditory and visual language tasks. With few
      exceptions, these studies have found low, nonsignificant correlations between the
      two types of perceptual asymmetries. However, variations in subjects' perceptual
      asymmetries on these tasks reflect not only individual differences in language
      lateralization but also several extraneous variables (e.g., random errors,
      individual differences in left-right attentional biases). Thus, low correlations
      between the two types of asymmetries may reflect "masking" by these extraneous
      variables rather than a "true" cross-modal dissociation. Consistent with this
      view, a meta-analysis of prior studies revealed a small, but significant
      correlation between the two types of asymmetries for left-handers. The
      correlation was nonsignificant for right-handers, presumably reflecting stronger
      attenuation caused by limited variability in language lateralization in this
      group. Possible factors mediating significant correlations between the two types
      of perceptual asymmetries include certain language processes shared by the two
      types of tasks, cross-modal consistency in individual differences in
      lateralization of certain modality-specific language processes, and cross-modal
      consistency in individual differences in left-right attentional biases.

PMID- 9184096
TI  - Reading errors following right hemisphere injection of sodium amobarbital.
AB  - The role of the nondominant hemisphere in reading is controversial. We
      characterized the reading errors made by 64 right-handed adults with complex
      partial seizures (half with seizure foci on the right and half on the left),
      after right hemisphere injection of sodium amobarbital. Subjects were presented
      with 20 six-word sentences and all were found to have speech associated with the
      left hemisphere only. A variety of reading errors occurred, most of which fell
      under the syndrome of "neglect dyslexia" including deletions and substitutions of
      whole words on the left side of a line of text as well as within-word neglect
      errors. The nature of these errors indicated that they may have been caused by an
      interaction between a peripheral processing deficit and more centrally located
      conceptual knowledge of linguistic structure. Other errors could be attributed to
      a general decrease in attentional mechanisms. Neglect errors at the level of the
      sentence occurred in the absence of neglect errors at the level of the word
      although the converse was not true. This suggests that the latter may represent a
      more severe deficit in the mechanism that causes the former. A double
      dissociation existed between single word neglect dyslexia errors and "visual"
      errors, indicating separate processing mechanisms.

PMID- 9184097
TI  - Analysis of conversational topic shifts: a multiple case study.
AB  - Investigation into the natural conversational discourse of patients with Dementia
      of the Alzheimer Type has received minimal attention, in part due to the inherent
      methodological problems. There are no satisfactory theoretical models of
      conversation; existing global checklists give minimal information on meaning
      relationships and analysis of conversation does not lend itself to group studies.
      The present study offered an initial example of how meaning relationships,
      expressed through topic shifting behavior, can be described in DAT and normal
      elderly subjects in natural conversational discourse. Categorization of topic
      units was done in an attempt to describe general phenomena, type of shift, reason
      for shift, and contextual relationship. Although very little differences were
      visually observed in the general categories, some convergence of data were
      observed in other topic shift categories. Discussion of the results in relation
      to a discourse processing model is presented.

PMID- 9184098
TI  - Hemispheric asymmetries in reading Korean: task matters.
AB  - Native Korean readers were studied in a visual half-field paradigm. Subjects were
      to make speeded judgments on Hangul (syllabic) and Hanzza (logographic) scripts
      based on phonetic or visual properties of the stimuli. A task by visual field
      interaction was obtained indicating that, for both scripts, responses on the
      phonetic task were faster in the right visual field, whereas no visual field
      differences were found on the visual task. Script type did not interact with
      visual field. The results support a task-based account of hemispheric differences
      in verbal processing.

PMID- 9184099
TI  - Ideomotor apraxia: behavioral dimensions and neuroanatomical basis.
AB  - Ideomotor apraxia, disordered movement execution to command, commonly follows
      left-hemisphere damage, implying left-hemisphere dominance for certain kinds of
      movements. To delineate this dominance we used different command modalities to
      elicit meaningful movements and tested imitation of nonsense movements. Twenty
      seven patients with unilateral hemispheric stroke and 10 age-matched controls
      were evaluated. Patients with left-hemisphere damage performed both meaningful
      and nonsense movements poorer than the other study groups; thus, the
      meaningfulness of the movements is irrelevant for the left-hemisphere motor
      dominance. The performance varied, however, with the command modality and
      movement type. Based on this and earlier studies we posit that the left
      hemisphere motor dominance is determined by the artificiality of the test
      situation (it concerns movements performed to command and out of the natural
      context) and increased spatial and temporal complexity of the demanded movements.
      No association between the lesion locus within the left hemisphere and the
      severity of the ideomotor apraxia was found.

PMID- 9184100
TI  - Cognitive neuropsychological analysis and neuroanatomic correlates in a case of
      acute anomia.
AB  - We describe an analysis of lexical processing performed in a patient with the
      acute onset of an isolated anomia. Based on a model of lexical processing, we
      evaluated hypotheses as to the source of the naming deficit. We observed
      impairments in oral and written picture naming and oral naming to definition with
      relatively intact semantic processing across input modalities, suggesting that
      output from the semantic system was impaired. In contrast to previous reports, we
      propose that this pattern represents an impairment that arises late in semantic
      processing prior to accessing mode-specific verbal and graphemic output lexicons.
      These deficits were associated with a lesion in the posterior portion of the
      middle temporal gyrus or area 37, an area of supramodal association cortex that
      is uniquely suited as a substrate for the multimodal deficit in naming.

PMID- 9184101
TI  - Language experience and right hemisphere tasks: the effects of scanning habits
      and multilingualism.
AB  - This study explores the effects of multilingualism and reading scanning habits on
      right hemisphere (RH) abilities. Native Hebrew speakers and Arabic-Hebrew
      bilinguals performed three tasks. Experiment 1 employed an odd/even decision
      paradigm on lateralized displays of bar graphs. Both groups of subjects displayed
      the expected LVFA within the range previously reported for readers of English.
      Experiment 2 consisted of a chair identification task designed to tap asymmetry
      of hemispheric arousal and a chimeric face task designed to tap RH specialization
      for facial emotion. Neither scanning habits nor language experience affected
      performance on the chair task. Scanning habits seem to have affected performance
      on the chimeric faces task: there was no preference for the left smile in these
      right-to-left readers, as opposed to previous results in the literature using
      left-to-right readers. Correlations between measures from the three tasks and all
      the subject's scores on an English proficiency test and on a Hebrew test for the
      bilinguals reveal tentative relationships between proficiency in a second
      language and RH abilities. The results do not support the hypothesis that
      multilingualism can affect the manner in which these nonlanguage tasks are
      subserved by the RH. They do support the hypothesis that scanning habits
      particular to specific languages can affect performance asymmetries on some
      nonlanguage tasks that have been posited to reflect RH specialization.

PMID- 9184102
TI  - Interaction between tone and intonation in Thai after unilateral brain damage.
AB  - Intonational characteristics of Thai sentences were used to evaluate fundamental
      frequency (F(0)) control in brain-damaged patients with unilateral left and right
      hemisphere lesions. Subjects (n = 41) included 9 young and 10 old normal adults,
      12 right hemisphere patients, and 10 left hemisphere aphasic patients (7 fluent
      and 3 nonfluent). Sentences were comprised of six words, three of which were
      keywords occurring in sentence-initial, -medial, and -final positions. All 125
      possible sequences of three of the five Thai tones (mid, low, falling, high,
      rising) were superimposed on monosyllabic keywords. Utterances were produced at a
      conversational speaking rate. Average F(0) of keywords was analyzed as a function
      of sentence position, tone, and group. For both normal and brain-damaged
      speakers, results indicated that tones in sentence-final position were
      significantly lower in F(0) than in either sentence-initial or -medial position;
      falling and high tones were significantly higher in F(0) than mid, low, and
      rising tones. Findings are discussed in relation to issues pertaining to
      hemispheric specialization and the nature of F(0) deficits in nonfluent and
      fluent aphasic patients.

PMID- 9184103
TI  - Functional MR imaging during auditory word perception: a single-trial
      presentation paradigm.

PMID- 9184105
TI  - Effects of tectal grafts on sound localization deficits induced by inferior
      colliculus lesions in hooded rats.
AB  - The goals of this research were to examine the role of the inferior colliculus
      (IC) in mediating sound localization behavior and the ability of tectal grafts to
      restore function after IC ablation in the Long-Evans rat. Previous work has
      suggested that the IC is a major center for processing of information used in
      localizing sound sources in space. Adult rats were trained on a lick suppression
      paradigm to discriminate the location of the second pulse in a noise burst pair
      presented in the horizontal interaural plane. Following baseline testing, rats
      received bilateral IC lesions, bilateral lesions followed in 1 week by bilateral
      tectal grafts, or were sham operated. Sound localization ability was then tested
      15 to 30 days and 40 to 50 days following surgical procedures. Performance across
      experimental groups was statistically the same during baseline testing. During
      the first operative test period lesion-only and grafted animals showed deficits
      in sound localization ability relative to controls. By the second postoperative
      test period control and grafted animals did not differ statistically in sound
      localization ability and performance of both groups was superior to that of
      lesion-only animals. Histology revealed a similar extent of IC damage in lesion
      only and lesion-graft animals and revealed the presence of implanted tectal
      tissue in all grafted animals. There was significant neuron loss in the dorsal
      nucleus of lateral lemniscus (DNLL) in lesion-only animals relative to grafted
      rats and sham controls. Behavioral results suggest that the IC of pigmented rat
      is important for sound localization ability. The sparing of DNLL neurons in
      grafted animals suggests that the tectal grafts may directly integrate into or
      aid intrinsic recovery of the host auditory pathway.

PMID- 9184104
TI  - Quantitative analysis of long-term survival and neuritogenesis in vitro:
      cochleovestibular ganglion of the chick embryo in BDNF, NT-3, NT-4/5, and
      insulin.
AB  - The dynamics of survival and growth were examined for cochleovestibular ganglion
      (CVG) cells maintained in long-term cultures. CVG cells were explanted from chick
      embryos after 90 h of incubation into a defined-medium containing BDNF, NT-3, or
      NT-4/5 and an insulin, transferrin, selenium, and progesterone supplement.
      Explant survival and neuritogenesis was measured for 23 to 24 days in vitro. All
      three neurotrophins prolonged CVG survival in a dose-dependent manner although
      insulin acted as a cofactor. In 0.872 microM insulin-containing medium the ED50
      for BDNF and NT-3 was 100 pg/ml, whereas the ED50 for NT-4/5 was 600-1200 pg/ml.
      However, at later ages in vitro, survival decreased with concentrations of BDNF
      greater than 2 ng/ml. In insulin-free medium, concentrations of 5-200 ng/ml of
      BDNF or 30-200 ng/ml of NT-4/5 maintained the survival of explants at a rate that
      was equivalent to or less than the survival rate of cultures treated with insulin
      but not with neurotrophin. In contrast, NT-3-treated explants in insulin-free
      medium did not survive the duration of the experiment. Dose-dependent effects of
      BDNF and NT-3 on explant neuritogenesis were reflected as an initial delay in
      outgrowth, whereas NT-4/5 had no effect. Insulin regulation of neuritogenesis was
      suggested when outgrowth decreased in the presence of an antibody to the insulin
      receptor. These data suggest that while all three of these neurotrophins protect
      the CVG from death the long-term consequences of cofactors and certain dose
      levels should be considered when treating CVG cells in vivo.

PMID- 9184106
TI  - Hyperplastic changes within the leptomeninges of the rat and monkey in response
      to chronic intracerebroventricular infusion of nerve growth factor.
AB  - Recombinant human nerve growth factor (rhNGF) was delivered for up to 6 months by
      continuous intracerebroventricular (i.c.v.) infusion to CD (Sprague-Dawley
      derived) rats and cynomolgus monkeys. Rats (n = 15/sex/group) received doses of 0
      (vehicle), 6, 60, or 300 ng/day; monkeys (n = 5/sex/group) received 0, 0.6, 6, or
      60 microg/day of rhNGF. Animals tolerated i.c.v. infusion with no behavioral
      signs attributable to rhNGF. Body weight was transiently decreased in female rats
      at the highest dose. At the completion of dosing, histological examination in
      both species revealed an increase in the thickness of the leptomeninges along the
      ventral and lateral surfaces of the hindbrain and extending over the dorsal
      aspect of the spinal cord. The change was present to varying degrees at all doses
      of rhNGF and tended to be more severe at higher doses. At the light microscopic
      level, the leptomeninges contained layers of well-differentiated, spindle-shaped
      cells and a plexus of axonal fibers. Cells were immunoreactive for S-100 protein
      and were associated with an accumulation of Type IV collagen, suggesting Schwann
      cell origin. Electron microscopy revealed numerous fine caliber axons ensheathed
      by the presumptive Schwann cells, with myelination of individual axonal segments.
      These findings suggest that chronic i.c.v. delivery of rhNGF has stimulated
      axonal sprouting and secondary hyperplasia of Schwann or Schwann-like support
      cells within the pia-arachnoid.

PMID- 9184107
TI  - 3-Nitropropionic acid increases the intracellular Ca2+ in cultured astrocytes by
      reverse operation of the Na+-Ca2+ exchanger.
AB  - The effect of 3-nitropropionic acid (3-NPA) on intracellular calcium ([Ca2+]i) in
      cultured cortical and striatal astrocytes was examined using a calcium imaging
      technique with fura-2. 3-NPA (1.7 mM) increased the [Ca2+]i in cortical and
      striatal astrocytes. The latency for the onset of the rise in [Ca2+]i in cortical
      astrocytes was 22.7 +/- 0.8 min and was significantly longer in striatal
      astrocytes (39.2 +/- 2.4 min; P < 0.001). The maximal increase in [Ca2+]i for
      both astrocytes was seen after 50 min and remained at that level even after
      extensive washing. The maximal responses were about 125 and 140% of the initial
      values for striatal and cortical cells, respectively. Pretreatment (2-3 h) with
      creatine (25 mM) significantly delayed the onset of increase in [Ca2+]i by 3-NPA
      in cortical (39.8 +/- 3.7 min) and in striatal (57.8 +/- 2.5 min) astrocytes from
      the respective untreated cells (P < 0.05). However, the [Ca2+]i increase was
      similar to that of the untreated cells at 60 or 90 min. The increase in [Ca2+]i
      by 3-NPA was not observed in Ca2+-free or low-Na+ medium, but there was rather a
      10-15% decrease under the Ca2+-free condition (P < 0.05). Superfusion of normal
      Ca2+ (2 mM) medium after exposure of the cells to 3-NPA in Ca2+-free medium
      increased the [Ca2+]i dramatically and reversibly. This increase was
      significantly attenuated in the presence of 2',4'-dichlorobenzamil (100 microM),
      nifedipine (10 microM), or Ni2+ (2 mM) or after exposure to amiloride (1 mM). The
      blockade was total in the case of 2',4'-dichlorobenzamil. The results indicate
      that the 3-NPA-induced increase in [Ca2+]i in astrocytes was due to an influx of
      Ca2+ by the reverse operation of the Na+-Ca2+ exchanger system, which may be
      responsible for the gliotoxic action of 3-NPA.

PMID- 9184108
TI  - Widespread neuronal ectopia associated with secondary defects in cerebrocortical
      chondroitin sulfate proteoglycans and basal lamina in MARCKS-deficient mice.
AB  - Mice deficient in MARCKS, a prominent neural substrate for protein kinase C
      (PKC), die before or shortly after birth. They exhibit high frequencies of
      exencephaly, universal agenesis of forebrain commissures, and abnormalities of
      cerebral cortical and retinal lamination. We show here that these mice have wide
      spread and severe neuronal ectopia in the outer layers of the developing
      forebrain, manifested by the migration of clusters of developing neuroblasts
      through the basal lamina and often through the pial membrane and into the
      subarachnoid space. This abnormality became apparent by Embryonic Day (E) 13 or
      14, shortly after the formation of the early marginal zone. MARCKS deficiency was
      associated with decreased staining for marginal zone chondroitin sulfate
      proteoglycans; this decrease was detectable earlier in development than the
      neuronal ectopia. Later in development, there was also marked disruption of the
      basal lamina at the pial-glial interface, as evidenced by gross abnormalities in
      laminin and reticulin staining; however, the basal lamina appeared normal at
      E9.5. These data indicate that MARCKS is required for the prevention of neuronal
      ectopia during development. Potential mechanisms responsible for the neuronal
      ectopia in the MARCKS-deficient mice include decreased expression or increased
      proteolytic destruction of basal lamina proteins and marginal zone chondroitin
      sulfate proteoglycans in the developing brain.

PMID- 9184109
TI  - Effects of BDNF infusion on the regulation of TrkB protein and message in adult
      rat brain.
AB  - Exposure of embryonic CNS neurons to BDNF in vitro causes down-regulation of TrkB
      protein and mRNA, and an attenuation of functional responses to acute
      neurotrophin stimulation. In order to investigate ligand-mediated regulation of
      TrkB in vivo, we infused BDNF into the midbrain, near the periaquaductal grey
      dorsal raphe (PAG-DR), or into the olfactory bulb of adult rats. Midbrain
      infusion of BDNF produced analgesia that was sustained for the duration of BDNF
      delivery. Analysis of TrkB receptor levels revealed that at the point when the
      maximal analgesic effect of BDNF was obtained, there was a concommitant 75%
      decrease in full-length TrkB protein at the infusion site. After discontinuation
      of infusion, levels of TrkB recovered toward base line. Interestingly, TrkB
      protein levels were not accompanied by decreased trkB mRNA levels. To determine
      if BDNF infusion decreased TrkB protein levels in other brain areas and whether
      trkB mRNA might be down-regulated in the cell bodies of neurons projecting to the
      infusion site, we infused BDNF into the olfactory bulb. Following a 12-day
      infusion of BDNF, TrkB protein levels decreased within the bulb to a similar
      extent as in the PAG-DR. This decrease in receptor protein, however, was not
      accompanied by decreased trkB mRNA levels in the olfactory cortex, which is
      afferent to the bulb. Taken together, our data suggest that decreases in TrkB
      receptor protein at the site of BDNF infusions in the adult brain represent
      receptor turnover, but this is not associated with altered expression of trkB
      mRNA or attenuation of the pharmacological effects of BDNF.

PMID- 9184110
TI  - Calcium-binding protein phenotype defines metabolically distinct groups of
      neurons in barrel cortex of behaving hamsters.
AB  - Physiological/anatomical studies of rat frontal cortex in vitro have
      distinguished subpopulations of gamma-aminobutyric acid (GABA)-expressing
      inhibitory interneurons defined by expression of the calcium-binding proteins,
      parvalbumin (PV) and calbindin (CA). Using a novel 2DG/immunostaining technique
      to double-label hamster barrel cortex for metabolism and phenotype, we have
      recently shown that while many GABAergic neurons are heavily 2DG labeled during
      normal exploratory behavior, a subset of GABAergic cells shows relatively sparse
      2DG labeling. For this study we used the 2DG/immunostaining technique to test
      whether, in awake behaving animals, calcium-binding protein expression in a given
      cell in barrel cortex (as indicated by immunohistochemistry for PV or CA) was
      related to the degree of 2DG labeling. We found that most PV+ cells were
      moderately to heavily 2DG labeled, while most CA+ cells were lightly 2DG labeled.
      Our data indicate that the PV+ and CA+ cells represent metabolically distinct
      subpopulations of GABAergic neurons in barrel cortex. This distinction
      corresponds well with the in vitro physiological and anatomical data from frontal
      cortex and suggests functional implications for the expression of PV and CA, or
      other colocalized factors, in normally functioning cortical circuitry.

PMID- 9184111
TI  - Induction of tumor suppressor p53 and DNA fragmentation in organotypic
      hippocampal cultures following excitotoxin treatment.
AB  - The p53 tumor suppressor gene encodes a cell cycle regulatory protein that is
      induced by DNA damage and has been implicated in apoptosis. To investigate
      whether excitotoxic cell death due to kainic acid (KA) and cell death due to N
      methyl-D-aspartate (NMDA) share similar molecular mechanisms, we studied p53
      expression and DNA fragmentation in organotypic hippocampal slice cultures
      following excitotoxin treatment. Cellular analyses showed that both p53 induction
      and DNA fragmentation occurred only in injured neurons following exposure to
      either excitotoxin. The temporal profiles of these changes demonstrated that p53
      induction preceded DNA fragmentation. The extent of regional alterations in p53
      expression and DNA fragmentation correlated with drug-related toxicity (i.e.,
      NMDA > KA). These results support the hypothesis that p53 is a marker of neuronal
      death in the CNS and suggest the possibility that excitotoxin-mediated neuronal
      death may occur through a p53-dependent pathway.

PMID- 9184112
TI  - Evidence that a positive modulator of AMPA-type glutamate receptors improves
      delayed recall in aged humans.
AB  - Elderly subjects (65-76 years) were tested for recall of nonsense syllables prior
      to and after oral administration of 1-(quinoxalin-6 ylcarbonyl)piperidine
      (CX516), a centrally active drug that enhances currents mediated by AMPA-type
      glutamate receptors. A significant and positive drug effect was found for delayed
      (5 min) recall at 75 min posttreatment; average scores for the highest dose group
      were more than twofold greater than for the placebo group. The drug had no
      evident influence on heart rate or self-assessment of several psychological
      variables.

PMID- 9184113
TI  - Suppressed kindling epileptogenesis and perturbed BDNF and TrkB gene regulation
      in NT-3 mutant mice.
AB  - In the kindling model of epilepsy, repeated electrical stimulations lead to
      progressive and permanent intensification of seizure activity. We find that the
      development of amygdala kindling is markedly retarded in mice heterozygous for a
      deletion of the neurotrophin-3 (NT-3) gene (NT-3+/- mice). These mice did not
      reach the fully kindled state (3rd grade 5 seizure) until after 28 +/- 4 days of
      stimulation compared to 17 +/- 2 days in the wild-type animals. The deficit in
      the NT-3+/- mice reflected dampening of the progression from focal to generalized
      seizures. The number of stimulations required to evoke focal (grade 1 and 2)
      seizures did not differ between the groups, but the NT-3 mutants spent a
      considerably longer period of time (13 +/- 3 days) than wild-type mice (2 +/- 1
      days) in grade 2 seizures. As assessed by test stimulation 4-12 weeks after the
      10th grade 5 seizure, kindling was maintained in the NT-3 mutants. In situ
      hybridization showed 30% reduction of basal NT-3 mRNA levels and lack of
      upregulation of TrkC mRNA expression at 2 h after a generalized seizure in
      dentate granule cells of the NT-3+/- mice, whereas the seizure-evoked increase in
      brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels was enhanced. These
      results indicate that endogenous NT-3 levels can influence the rate of
      epileptogenesis, and suggest a link between NT-3 and BDNF gene regulation in
      dentate granule cells.

PMID- 9184114
TI  - Intracerebroventricular glial cell line-derived neurotrophic factor improves
      motor function and supports nigrostriatal dopamine neurons in bilaterally 6
      hydroxydopamine lesioned rats.
AB  - In order to evaluate the efficacy of glial cell line-derived neurotrophic factor
      (GDNF) in a model of advanced Parkinson's disease, we studied rats with extensive
      bilateral lesions of the nigrostriatal pathway. Adult male F344 rats were
      injected bilaterally into the medial forebrain bundle with the neurotoxin 6
      hydroxydopamine. Locomotor ability as measured by total distance traveled in an
      open field over 20 min, as well as von Frey hair testing of sensorimotor neglect,
      was monitored weekly. Rats demonstrating severe motor impairment and sensorimotor
      neglect were used for this study and were sorted to achieve similar average
      behavioral scores between the two treatment groups. After 2 weeks of pretesting,
      the rats received 250 microg GDNF or vehicle injected into the right lateral
      cerebral ventricle. Three weeks later, an additional 500 microg GDNF or vehicle
      was injected into the contralateral ventricle. The rats were monitored for
      another 2 weeks prior to sacrifice. Behavioral results indicated that von Frey
      hair scores were inconsistent between tests for each rat and were unchanged
      following GDNF treatment. However, GDNF recipients demonstrated significant
      improvement in locomotor ability compared to vehicle recipients. High-pressure
      liquid chromatography-electrochemical detection analysis of neurotransmitter
      levels revealed a significant increase in dopamine content within the substantia
      nigra and ventral tegmenta, but not the striata, of GDNF-treated rats. Further,
      immunohistochemical staining of tissues from matched pairs of rats revealed
      increased numbers of tyrosine hydroxylase-positive ventral mesencephalic neurons
      in one of the two pairs of rats examined. These results suggest that
      intracerebroventricular GDNF administration improves motor ability and supports
      nigrostriatal dopaminergic neurons in a model of severe Parkinson's disease.

PMID- 9184116
TI  - Somatic delivery of catecholamines in the striatum attenuate parkinsonian
      symptoms and widen the therapeutic window of oral sinemet in rats.
AB  - Guidelines for clinical transplantation studies for Parkinson's disease emphasize
      that transplants should be considered as an adjunct to systemic L-DOPA, yet few
      preclinical studies have specifically assessed the potential of transplants as an
      adjunct to the clinical gold standard treatment. The objectives of the present
      study were to determine if encapsulated PC12 cells implanted in rats with severe
      unilateral dopamine depletions: (i) have a direct therapeutic effect on measures
      of parkinsonian symptoms; and/or (ii) increase the therapeutic window of oral
      sinemet in this model. Rats with severe unilateral dopamine depletions received
      striatal implants of encapsulated PC12 cells producing dopamine and L-DOPA. These
      rats were tested on a battery of behavioral measures of parkinsonian symptoms, at
      a range of doses of oral sinemet (0, 12, 24, and 36 mg/kg).
      Stereotypies/dyskinesias were also quantified after high doses of oral sinemet
      (36 and 50 mg/kg). The results confirm that parkinsonian symptoms can be
      quantified in rats with severe dopamine depletions, and the validity and clinical
      relevance of these measures are supported by the fact that the clinical gold
      standard treatment, oral sinemet, attenuates these parkinsonian symptoms. Somatic
      delivery of dopamine and L-DOPA, directly to the dopamine-depleted striatum, also
      attenuates parkinsonian symptoms. In fact, the magnitude of the therapeutic
      effect produced by continuous, site-specific, somatic delivery of dopamine and L
      DOPA was larger than the effect produced by acute, systemic, oral sinemet. The
      beneficial effects of oral sinemet and striatal implants of catecholamine
      producing devices were additive, but there were no adverse effects related to
      striatal catecholamine-producing devices, and these devices did not increase the
      adverse effects related to oral sinemet. Therefore, striatal implants of
      catecholamine-producing devices have direct therapeutic effects which are fairly
      robust, and they widen the therapeutic window of oral sinemet.

PMID- 9184115
TI  - Long-term reciprocal changes in dopamine levels in prefrontal cortex versus
      nucleus accumbens in rats born by Caesarean section compared to vaginal birth.
AB  - Epidemiological evidence indicates a higher incidence of pregnancy and birth
      complications among individuals who later develop schizophrenia, a disorder
      linked to alterations in mesolimbic dopamine (DA) function. Two birth
      complications usually included in these epidemiological studies, and still
      frequently encountered in the general population, are birth by Caesarean section
      (C-section) and fetal asphyxia. To test the hypothesis that birth complications
      can produce long-lasting changes in DA systems, the present study examined the
      effects of Caesarean birth, with or without an added period of anoxia, on steady
      state monoamine levels and metabolism in various brain regions in a rat model.
      Pups born vaginally served as controls. At 2 months of age, in animals born by
      rapid C-section, steady state levels of DA were decreased by 53% in the
      prefrontal cortex and increased by 40% in both the nucleus accumbens and
      striatum, in comparison to the vaginally born group. DA turnover increased in the
      prefrontal cortex, decreased in the nucleus accumbens, and showed no significant
      change in the striatum, in the C-section group. Thus, birth by a Caesarean
      procedure produces long-term reciprocal changes in DA levels and metabolism in
      the nucleus accumbens and prefrontal cortex. This is consistent with the known
      inhibitory effect of increased prefrontal cortex DA activity on DA release in the
      nucleus accumbens. By contrast to birth by rapid C-section alone, young adult
      animals, that had been born by C-section with 15 min of added anoxia, showed no
      change in steady state DA levels in the prefrontal cortex, nucleus accumbens, or
      striatum and a significant decrease in DA turnover only in the nucleus accumbens,
      in comparison to the vaginally born group. Levels of norepinephrine, serotonin,
      and its metabolite, 5-hydroxyindole acetic acid, were unchanged in all groups,
      indicating relatively specific effects on DA systems. Although appearing robust
      at birth on gross observation, more subtle measurements revealed that rat pups
      born by C-section show altered respiratory rates and activity levels and
      increased levels of whole brain lactate, suggestive of low grade brain hypoxia,
      during the first 24 h of life, in comparison to vaginally born controls. Pups
      born by C-section with 15 min of added acute anoxia were pale, hypotonic, and
      inactive at birth and showed reduced respiration and high brain lactate levels.
      However, these alterations resolved by 1-5 h after birth and, with few
      exceptions, animals in the anoxic group remained normal with respect to these
      parameters during the remainder of the first 24 h of life. Immediately after
      birth, levels of plasma epinephrine, a hormone known to play a role in neonatal
      adaptation to extrauterine life and protection against hypoxia, were decreased in
      pups born by C-section but increased in pups born by C-section with 15 min added
      anoxia, in comparison to levels measured in vaginally born controls. These early
      developmental alterations could contribute to long-term alterations in
      dopaminergic parameters observed in rats born by C-section, with or without added
      anoxia. It is concluded that C-section birth is sufficient perturbation to
      produce long-lasting effects on DA levels and metabolism in the central nervous
      system of the rat. These findings highlight the sensitivity of DA pathways to
      variations in birth procedure and support the notion that birth complications
      might contribute to the pathophysiology of disorders involving central
      dopaminergic neurons, such as schizophrenia.

PMID- 9184117
TI  - Seizure-induced damage to somatostatin-immunoreactive neurons in the rat
      hippocampus is regulated by fimbria-fornix transection.
AB  - In both experimental and human temporal lobe epilepsy, seizures cause loss of
      hilar somatostatin-immunoreactive (SOM-ir) neurons and sprouting of mossy fibers.
      To investigate whether in rats these alterations are modulated by hippocampal
      input projections, we transected the fimbria-fornix or the perforant pathway
      bilaterally 2 days after seizures induced by systemic administration of kainic
      acid (9 mg/kg, i.p.). Two months later, the number of SOM-ir neurons in the hilus
      was counted and mossy fiber sprouting in the supragranular area and in the inner
      molecular layer was analyzed. In seizured rats with sham-operation, 50% of the
      hilar SOM-ir neurons were left in the septal end of the hippocampus and only 16%
      remained in the temporal end. In seizured rats with transection of the fimbria
      fornix, the number of hilar SOM-ir neurons in the septal end of the hippocampus
      did not differ from that in controls (98% of SOM-ir neurons left). However, the
      temporal end was severely damaged (41% of SOM-ir neurons left). In seizured rats
      with transection of the perforant pathway, 61% of the hilar SOM-ir neurons were
      left in the septal end and 51% in the temporal end of the hippocampus. Mossy
      fiber sprouting was evident throughout the septotemporal axis of the hippocampus
      in all seizured rats. Our results suggest that in the septal end of the
      hippocampus the severity of neuronal damage in the hilus is modulated by
      mechanism(s) that are dependent on the afferent pathways entering the hippocampus
      via the fimbria-fornix. Transection of the fimbria-fornix, however, does not
      significantly modulate the severity or the target regions of seizure-induced
      sprouting of mossy fibers.

PMID- 9184118
TI  - Hippocampal connexin 43 expression in human complex partial seizure disorder.
AB  - An increase in the cellular production of gap junction proteins and increased
      numbers of gap junctions in the neuronoglial syncytium of an epileptic focus have
      been proposed as a possible mechanism underlying synchronization of discharge. To
      study this issue, both Northern and Western blot analyses of the gap junction
      protein connexin 43 mRNA and protein abundance were performed on hippocampal
      tissue resected from patients presenting with a complex partial seizure disorder
      arising from the medial temporal area and the hippocampus in particular. Samples
      from 15 patients with medically intractable seizures were compared to those from
      5 nonepileptic patients requiring temporal lobectomy in life-threatening
      situations. Six of the 15 epileptic patients underwent noninvasive electrographic
      recording, whereas the remaining 9 patients required intracerebral electrodes for
      extraoperative recording and therefore showed a more discrete focality than the
      noninvasive recordings. A decline in the mean levels of connexin 43 mRNA
      expressed predominantly in astrocytes was noted in the epileptic patient groups,
      particularly for those cases requiring intracranial electrode placement where
      ictal onset was more clearly established to be intrahippocampal. Quantitation of
      connexin 43 protein in both epileptogenic and nonepileptogenic hippocampal
      tissues showed no significant differences in expression. Although mean values for
      mRNA showed a decline, clinical outcomes postoperatively showed no correlation
      with either mRNA or protein expression individually in our epileptic population.
      The findings indicate that there is effectively no upregulation of mRNA and no
      increased production of connexin 43 protein in response to the development of
      epileptogenicity. Rather it appears the influence of gap junctions as a substrate
      of epileptogenicity in any mechanism(s) underlying synchrony or electrical
      propagation may be a function of the dynamic state (open versus closed) of the
      membrane-bound gap junction.

PMID- 9184119
TI  - Spinal cord gray matter layers rich in NADPH diaphorase-positive neurons are
      refractory to ischemia-reperfusion-induced injury: a histochemical and silver
      impregnation study in rabbit.
AB  - Silver impregnation analysis of neuronal damage and concurrent histochemical
      characterization of NADPH diaphorase-positive neuronal pools in the rabbit
      lumbosacral segments was performed during and after transient spinal cord
      ischemia. Strongly enhanced staining of NADPH diaphorase-positive neurons and
      their processes appeared in the superficial dorsal horn (laminae I-III), the
      pericentral region (lamina X) of lower lumbar segments, the lateral collateral
      pathway, and mainly in neurons of the sacral parasympathetic nucleus in the S2
      segment at the end of 40 min of abdominal aorta ligation or 1 day after
      reperfusion. Despite the development of extensive neuronal degeneration in the
      central gray matter (laminae IV-VII) between 1 and 4 days after ischemia, a
      number of nonnecrotizing neurons localized in the areas corresponding with the
      distribution of NADPH diaphorase-positive neurons was detected, suggesting a
      selective resistance of these classes of neurons against transient ischemic
      insult. While the precise mechanism of the observed resistance is not known, it
      is postulated that region-specific synthesis of nitric oxide and its
      vasodilatatory effect during the period of incomplete spinal ischemia may account
      for the observed selective resistance of these spinal cord neurons to transient
      ischemia.

PMID- 9184120
TI  - Expression of endothelin-B receptors by glia in vivo is increased after CNS
      injury in rats, rabbits, and humans.
AB  - Previous studies have demonstrated that neonatal cultures of astrocytes express
      functional endothelin (ET) receptors. To determine if similar ET receptors are
      expressed by adult glia we used 125I-ET-1 to examine the expression of ET
      receptors both in vivo in the normal and transected optic nerves of the rabbit
      and rat and in vitro in cultures of astrocytes, microglia, or oligodendrocytes.
      Additionally, we examined the expression of ET receptors in the human optic
      nerve. Moderate levels of ET(B) receptors were identified in the rabbit and rat
      forebrain, whereas in the normal rabbit, rat, and human optic nerves a low
      density of ET(B) receptors was observed, mainly in association with glial
      fibrillary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve
      transection, or damage to the retina, the density of glial ET(B) receptors in the
      optic nerve is significantly increased in all species examined. Thus, at 7 days
      posttransection there is a significant increase in ET(B) receptors, and by 90
      days posttransection the density of ET(B) receptors in the rabbit or rat optic
      nerve was among the highest of any area in the central nervous system (CNS).
      Primary cultures of astrocytes or microglia, but not oligodendrocytes, express
      125I-ET-1 binding sites. These data demonstrate that in the normal CNS,
      astrocytes express low but detectable levels of ET(B) receptors, and, after CNS
      injury, both astrocytes and microglia express high levels of ET(B) receptors.
      ET(B) receptors provide a therapeutic target for regulating glial proliferation
      and the release of neurotrophic factors from glia that occur in response to
      neuronal injury.

PMID- 9184121
TI  - Growth cones turn up concentration gradients of diffusible peripheral target
      derived factors.
AB  - Severed peripheral nerve axons grow across a gap in their pathway to regenerate
      into the distal nerve stump. At the turn of the century this observation led to
      the proposal that concentration gradients of factors released from the cells of
      the distal nerve segment orient the growth of the regenerating axons. Recently,
      several central nervous system target-derived factors have been shown to direct
      process outgrowth via concentration gradients of the factors during development.
      The demonstration of target-derived tropic influences in the peripheral nervous
      system has however remained elusive. We have examined whether concentration
      gradients of diffusible factors released by the cells of a length of peripheral
      nerve influence the outgrowth of adult sensory neuron growth cones in vitro. We
      demonstrate that the growth cones turn and grow up the concentration gradients,
      providing evidence for the presence of diffusible peripheral target-derived
      neurotropic factors that can act in the peripheral nervous system.

PMID- 9184122
TI  - Correlated axonal sprouting and dendritic spine formation during kainate-induced
      neuronal morphogenesis in the dentate gyrus of adult mice.
AB  - Several examples of structural plasticity in the adult brain have been provided
      in the hippocampus, among which the most striking concerns axonal remodeling of
      the dentate gyrus granule cells. We have recently demonstrated that a single
      injection of kainic acid into the dorsal hippocampus of adult mice triggers a
      conspicuous morphogenetic response of granule cells. Cellular labeling with
      biocytin 1, 2, and 4 weeks after injection of kainate revealed a progressive
      increase in dendritic thickness and length (up to 2.5-times), combined with an
      increase in the number of dendritic spines. This correlation resulted in the
      conservation of total spine density. No modifications of the dendritic
      arborization pattern were noted. In addition to dendritic changes, the number of
      axonal profiles observed within the hypertrophied granular layer and the inner
      part of the molecular layer appeared dramatically increased. Timm staining and
      anterograde labeling of two of the main extra-hippocampal afferent systems (i.e.,
      septal, entorhinal) evidenced sprouting of mossy fibers and of septal afferents.
      Entorhinal fibers were not obviously modified. As revealed by calretinin
      immunohistochemistry, commissural afferents also responded by an extensive
      sprouting. In addition, increases of dendritic spine number and dendritic length
      were noticeably greater in portions of dendrites that receive mossy fiber
      collaterals and septal and hypothalamic afferents, than in the external portion
      which receives entorhinal afferents. Although qualitative, this correlation
      suggests a relationship between kainate-induced structural plasticity of mature
      granule cells and the specific capacities of afferent systems to elaborate axon
      collaterals.

PMID- 9184124
TI  - Postnatal ontogeny of striatal-enriched protein tyrosine phosphatase (STEP) in
      rat striatum.
AB  - The present study was undertaken to examine developmental change in expression of
      striatal-enriched protein tyrosine phosphatase (STEP) in the postnatal striatum
      of rats. For this purpose, immunohistochemical staining and transimmunoblotting
      analyses were carried out using a cDNA-generated polyclonal antibody to the STEP
      with a molecular weight of 46 kDa. Immunostaining showed that in neonatal
      striatum STEP-immunoreactivity was found in discrete patches composed of many
      immature cells, which corresponded to the tyrosine hydroxylase-immunopositive
      "dopamine islands." With development there was an increase in staining intensity
      and in the number of positively reacting cells. By 4 weeks postnatally, STEP
      immunoreactivity was almost homogeneously distributed throughout the striatum, as
      was seen at the adult stage. Immunoblotting analysis showed that STEP protein
      expression abruptly increased from 2 to 4 weeks postnatally when it reached the
      adult level. These findings suggest that STEP is involved in development and
      maturation of the striatal neurons.

PMID- 9184123
TI  - Co-transplantation of fetal lateral ganglionic eminence and ventral mesencephalon
      can augment function and development of intrastriatal transplants.
AB  - Methods to increase the development and sustained function of embryonic
      mesencephalic dopamine cells after transplantation into dopamine (DA)-depleted
      striatum are currently under investigation. Elements that are crucial for the
      maturation and connectivity of neurons during normal development of the brain may
      also play a role in the development and integration of grafted embryonic tissue.
      Based on in vitro and in vivo observations of the enhancing effects of striatal
      tissue on nigral dopaminergic cell development and survival, we demonstrate that
      inclusion of embryonic striatal cells, specifically from the lateral ganglionic
      eminence (LGE), produces dopaminergic transplants with augmented functional
      effects. Rats neonatally DA-depleted and co-transplanted with embryonic nigral
      and LGE cells developed improved functional outcome when compared with animals
      receiving only nigral cells, and they required the transplantation of fewer
      nigral cells to produce a strong behavioral effect. Anatomically, the inclusion
      of LGE cells produced increased DA cell survival, a higher density of
      reinnervation into the DA-depleted host striatum, and patches of DA fibers within
      the co-transplants. There were also an increased number of host striatal cells
      which induced the immediate-early gene c-fos in co-transplanted animals compared
      to animals receiving nigral cells alone, indicating a higher degree of host-cell
      activation. The ability to enhance function, cell survival, reinnervation, and
      host activation with nigral-striatal co-transplants in the presence of fewer
      nigral cells supports the hypothesis of a trophic influence of striatal cells on
      nigral DA cells.

PMID- 9184125
TI  - Glycine causes increased excitability and neurotoxicity by activation of NMDA
      receptors in the hippocampus.
AB  - Glycine is an inhibitory neurotransmitter in the spinal cord and also acts as a
      permissive cofactor required for activation of the N-methyl-D-aspartate (NMDA)
      receptor. We have found that high concentrations of glycine (10 mM) cause marked
      hyperexcitability and neurotoxicity in organotypic hippocampal slice cultures.
      The hyperexcitability, measured using intracellular recording in CA1 pyramidal
      neurons was completely blocked by the NMDA receptor antagonist MK-801 (10
      microM), but not by the AMPA receptor antagonist DNQX (100 microM). The
      neurotoxicity caused by glycine occurred in all regions of hippocampal cultures
      but was most marked in area CA1. There was significant CA1 neuronal damage in
      cultures exposed to 10 mM glycine for 30 min or longer (P < 0.01) or those
      exposed to 4 mM glycine for 24 h compared to control cultures (P < 0.01). The
      NMDA antagonists MK-801 (10 microM) and APV (100 microM) significantly reduced
      glycine-induced neuronal damage in all hippocampal subfields (P < 0.01). The AMPA
      antagonists CNQX, DNQX, and NBQX (100 microM) had no effect on glycine-induced
      neuronal damage. High concentrations of glycine therefore appear to enhance the
      excitability of hippocampal slices in an NMDA receptor-dependent manner. The
      neurotoxic actions of glycine are also blocked by NMDA receptor antagonists.

PMID- 9184127
TI  - Blood-brain barrier permeability during the development of experimental bacterial
      meningitis in the rat.
AB  - In an attempt to examine whether routes of bacterial entry into the central
      nervous system have any bearing on subsequent changes in blood-brain barrier
      permeability, we examined cerebrospinal fluid (CSF) penetration of circulating
      125I-albumin in two different models of experimental meningitis due to K1
      Escherichia coli, type III group B streptococcus, or Haemophilus influenzae type
      b in infant rats: hematogenous meningitis subsequent to subcutaneous inoculation
      of bacteria vs meningitis induced by direct inoculation of bacteria into the CSF
      via the cisterna magna. In the model of hematogenous meningitis, the mean CSF
      penetration was significantly greater in animals with H. influenzae type b
      meningitis than in those with meningitis due to K1 E. coli or type III group B
      streptococcus. In contrast, the mean CSF penetration was significantly enhanced
      in all animals with meningitis induced by intracisternal inoculation regardless
      of infecting pathogens. Tumor necrosis factor activity in CSF appeared to
      correlate with the functional penetration of circulating albumin across the blood
      brain barrier in both models of experimental meningitis. These findings suggest
      that the alterations of blood-brain barrier permeability during development of
      experimental meningitis may vary for different models of inducing meningitis and
      that the mechanisms responsible for these different permeability changes may be
      multifactorial.

PMID- 9184126
TI  - Decreased TrkA gene expression in cholinergic neurons of the striatum and basal
      forebrain of patients with Alzheimer's disease.
AB  - In addition to cortical pathology, Alzheimer's disease is characterized by a loss
      of cholinergic neurons in the basal forebrain and the ventral striatum. Since
      cholinergic neurons which degenerate in Alzheimer's disease are sensitive to
      nerve growth factor, a link between nerve growth factor sensitivity and the
      vulnerability of cholinergic neurons has been suspected. The purpose of this
      study was to determine, in cholinergic neurons, the level of expression of TrkA,
      the high affinity receptor for nerve growth factor, in control subjects and
      Alzheimer patients. The study was performed by in situ hybridization using a 35S
      labeled RNA probe complementary to human TrkA mRNA on immunohistochemically
      identified cholinergic neurons of the nucleus basalis of Meynert, the ventral
      striatum, and the putamen in postmortem brains of patients with clinically and
      neuropathologically confirmed Alzheimer's disease and control subjects. In
      patients with Alzheimer's disease, a decrease in TrkA mRNA expression was
      observed in the nucleus basalis of Meynert (-75%, P < 0.001) and the ventral
      striatum (-41%, P < 0.01), where the cholinergic neurons degenerate, and also in
      the anterior (-43%, P < 0.01) and posterior (-51%, P < 0.01) parts of the
      putamen, where they are spared but display precocious signs of cell alterations.
      These results, taken in conjunction with the reduced choline acetyltransferase
      activity and our previously published data showing a loss of high affinity nerve
      growth factor binding in both the dorsal and the ventral striatum of patients
      with Alzheimer's disease, indicate that receptor loss and the consequent decrease
      in trophic support may be associated with the degeneration of cholinergic neurons
      during Alzheimer's disease.

PMID- 9184128
TI  - The superimposed effects of chronic phrenicotomy and cervical spinal cord
      hemisection on synaptic cytoarchitecture in the rat phrenic nucleus.
AB  - The present study was carried out to determine the effects of a combined
      peripheral phrenicotomy and rostral spinal cord hemisection on the synaptic
      architecture in the ipsilateral rat phrenic nucleus. Young adult female Sprague
      Dawley rats were divided into a hemisection-alone and two hemisection-plus
      phrenicotomy (HPP) groups. In all animals, DiI, a fluorescent carbocyanine dye
      was injected into the left hemidiaphragm to retrogradely label the ipsilateral
      phrenic motoneurons. In the HPP groups, left intrathoracic phrenicotomies were
      carried out at 2 and 4 weeks prior to sacrificing. Hemisection-alone animals were
      not subjected to phrenicotomy. In all animals, a left C2 spinal cord hemisection
      was performed 24 h prior to death. Quantitative morphometric analysis of the
      phrenic nucleus showed that the number of synapses contacting phrenic profiles is
      significantly less in the HPP (2 week) group as compared to the hemisection-alone
      group, but this number returns to a level not significantly different from the
      hemisection-alone value in the HPP (4 week) group. The results suggest that the
      transient change in the number of synapses might contribute to the differential
      expression of the crossed phrenic phenomenon documented in another group of
      animals subjected to the same surgical procedures. Furthermore, the different
      stages of glial reaction induced by phrenicotomy/spinal cord hemisection might
      underlie the change in synaptic number.

PMID- 9184129
TI  - Functional interactions between spinal cord grafts suggest asymmetries dictated
      by graft maturity.
AB  - Fetal spinal cord tissue grafts have been advocated as a possible repair strategy
      for spinal cord injury. In the present study, we used intraocular spinal cord
      grafts to model the interactions which may occur between fetal and adult spinal
      cord after making such a graft and to study to which extent functional
      connections can be expected to occur between the host and graft tissue. We first
      grafted fetal spinal cord to the anterior chamber of the eye where it was allowed
      to mature. A second piece of fetal spinal cord was then sequentially grafted in
      contact with the first graft. Electrophysiological recordings made from the older
      graft while electrically stimulating the younger graft provided evidence for an
      excitatory innervation from the younger spinal cord graft to the mature spinal
      cord which appeared to be glutamatergic. However, we only rarely found excitatory
      inputs from the first, mature spinal cord graft to the younger graft. Fiber
      connections between the two spinal cord grafts were verified by retrograde
      tracing and neurofilament immunohistochemistry. In no case was a trophic
      influence on graft volume observed between spinal cord grafts regardless of
      whether the transplantations were performed sequentially or at the same time.
      Even the introduction of a second graft to immature spinal cord tissue was
      ineffective. In contrast, we found a marked trophic, neuron-rescuing effect of
      spinal cord grafts upon cografts of fetal dorsal root ganglia. This latter
      observation is consistent with the hypothesis that spinal cord tissue can exert a
      trophic effect on developing sensory ganglia and demonstrates that many sensory
      neurons can survive in the presence of a central target and in the absence of the
      appropriate peripheral target. These intraocular experiments predict that fetal
      spinal cord grafted to the injured adult spinal cord may develop effective
      excitatory inputs with the host, while host-to-graft inputs may develop to a
      considerably smaller extent. Our results also suggest that the adult spinal cord
      does not exert marked trophic effects on growth of fetal spinal cord, while it
      does exert a trophic influence on central projections of dorsal root ganglia.

PMID- 9184130
TI  - Neurite outgrowth is enhanced by anti-idiotypic monoclonal antibodies to the
      ganglioside GM1.
AB  - Exogenously added gangliosides enhance sprouting, neurite outgrowth, and other
      neuronal activities; this effect may be initiated when a ganglioside binds to a
      membrane protein or when a ganglioside intercalates into the plasma membrane. To
      test whether binding to membrane proteins is sufficient for ganglioside-mediated
      activity, anti-idiotypic antibodies were generated that mimic the functional
      binding sites of the ganglioside GM1 as described by M. J. Riggott and W. D.
      Matthew (1996, Glycobiology, 6, 581-589). These anti-idiotypic antibodies are
      proteinaceous probes that model the biochemical and biological effects of
      gangliosides. Those anti-idiotypic ganglioside (AIG) monoclonal antibodies
      (mAb's) were selected based on their ability to bind a known GM1 binding protein,
      the beta-subunit of cholera toxin. These studies described neuronal cell surface
      proteins that were identified by immunocytochemistry and Western blotting using
      these AIG mAb's. Here we show that AIG mAb's mimic the functional properties of
      GM1 in that they facilitate neurite outgrowth from central and peripheral nervous
      system neurons in in vitro bioassays. In addition, AIG mAb binding modulates
      second messenger activity, suggesting that membrane protein binding alone is
      sufficient to invoke intracellular activation. The similarity in the pattern of
      protein tyrosine phosphorylation evoked by GM1 and the anti-idiotypic ganglioside
      antibodies suggests that the AIG mAb's modulate neurite outgrowth in a manner
      similar to that of GM1. Because antibodies cannot intercalate into the plasma
      membrane, these results suggest that the ganglioside GM1 can mediate neuronal
      cellular activity by binding to cell surface proteins.

PMID- 9184131
TI  - Haloperidol decreases hyperkinetic paw treading induced by globus pallidus
      lesions in the rat.
AB  - Systemic haloperidol injections decrease the severity of several hyperkinetic
      syndromes caused by damage to the basal ganglia in humans. A model of
      hyperkinesia in the rat, exaggerated paw treading triggered by oral sensory
      stimulation, has been reported previously to result from lesions of the globus
      pallidus or ventral pallidum/substantia innominata. This hyperkinesia appears as
      forepaw and forelimb extension and retraction, which can be emitted vigorously
      and repeatedly for up to minutes at a time. The present study aimed to discover
      whether this experimental hyperkinesia is pharmacologically similar to human
      hyperkinetic syndromes: can it be suppressed by neuroleptic administration?
      Systemic injections of haloperidol (2 mg/kg), diazepam (5 mg/kg, as a sedative
      comparison), or vehicle were given to rats that expressed the paw treading
      syndrome after pallidal lesions. Effects on hyperkinetic treading and on tests of
      sensorimotor function were compared. Results indicated that haloperidol was
      effective in ameliorating the hyperkinesia in rats with bilateral globus pallidus
      lesions but not in rats with ventral pallidum/substantia innominata lesions. By
      contrast, diazepam, which produced sedation and sensorimotor impairment, did not
      decrease the hyperkinesia induced by either lesion. Although only haloperidol
      decreased hyperkinetic treading after globus pallidus lesions, haloperidol
      produced less of a sensorimotor impairment than diazepam on climbing, hanging,
      and righting reflex tests. These results implicate a specific role for dopamine
      neurotransmission in the expression of triggered hyperkinetic treading induced by
      globus pallidus lesions.

PMID- 9184132
TI  - The cellular basis for the relative resistance of parvalbumin and calretinin
      immunoreactive neocortical neurons to the pathology of Alzheimer's disease.
AB  - The vulnerability of nerve cells to the neurofibrillary pathology of Alzheimer's
      disease (AD) may be determined by the presence within them of certain
      cytoskeletal proteins. Fluorescence multiple labeling was used to assess the
      vulnerability of two separate subpopulations of nonpyramidal neurons in the
      superior frontal gyrus, distinguished by their content of the calcium-binding
      proteins parvalbumin (PV) and calretinin (CR), to the neuropathology of AD. In
      AD, counterstaining PV- and CR-labeled sections with thioflavine S demonstrated
      that the great majority of these cells did not contain neurofibrillary tangles,
      except for the large CR-immunoreactive neurons in layer I. This latter group of
      cells was also characterized as containing neurofilament (NF) triplet proteins,
      whereas other CR-labeled cortical neurons were not immunoreactive for NF. There
      was also a small AD-related increase in the proportion of PV-labeled cells
      showing NF protein immunoreactivity (1-9% of the total population in AD cases
      compared to 0-0.4% in non-AD cases), which likewise may be linked to the
      susceptibility of a minute proportion (0-0.7%) of these neurons to form
      neurofibrillary tangles in AD. These data are further evidence that the presence
      of NF in cortical nerve cells is linked to their vulnerability to the
      pathological process underlying AD.

PMID- 9184133
TI  - Repeated cold water swim produces delayed nociceptive responses, but not
      analgesia, for tonic pain in the rat.
AB  - Earlier studies have demonstrated that cold water swim (CWS) produces stress
      induced analgesia in tests of brief, phasic pain and produces a delayed
      nociceptive response (DNR) for more prolonged tonic pain. The present study
      reports the effect of repeated CWS on tonic pain, as measured by the formalin
      test. One group of rats was exposed to a 3.5-min swim in 2 degrees C water
      immediately prior to the formalin injection, to a 1.5-min swim at 50 min, and to
      another 1.5-min swim at 100 min postformalin injection. Compared to the no-swim
      control group, subjects which received repeated CWS had dramatically altered
      formalin pain responses. Formalin responses began just over 3 h postformalin
      injection, peaked at 4 h, and were still present at 5 h. Inspection of individual
      responses revealed a substantial degree of variability in the onset of responses,
      although the magnitude and duration of the formalin pain response remained at the
      same levels as those of control subjects. The lack of a decrease in the magnitude
      and duration of the delayed formalin responses indicates that repeated CWS does
      not produce analgesia for tonic pain. The period of stress, therefore, produces
      pain suppression but not loss of the mechanisms that subsequently underlie the
      pain. Earlier controls have ruled out peripheral mechanisms (such as retention of
      the formalin in the paw tissue). Rather, a memory mechanism appears to have been
      indicated and it is not lost, but persists until it can be manifested. Further
      research is needed to study the mechanisms responsible for the DNR.

PMID- 9184134
TI  - 5'-RNA self-capping from guanosine diphosphate.
AB  - A selected RNA (isolate 6) efficiently catalyzes a self-capping reaction with
      free GDP, yielding the same 5'-capped structure as is formed by protein GTP:RNA
      guanylyltransferase. This unexplored RNA-catalyzed reaction type involving
      nucleophilic attack on phosphate by phosphate adds to the variety of possible
      postsynthetic RNA-catalyzed RNA modifications. The selected RNA requires only
      Ca2+ for activation and has a broad active pH range of 4.5-9.0. The RNA also has
      a 5'-pyrophosphatase activity.

PMID- 9184135
TI  - Association of cytosolic Rab4 with GDI isoforms in insulin-sensitive 3T3-L1
      adipocytes.
AB  - Translocation of an intracellular pool of GLUT4 glucose transporters to the fat
      and muscle cell surface is thought to involve small GTP-binding proteins such as
      the Rab4 protein. The cycling of Rab proteins between cytosol and intracellular
      membranes necessary for their function appears to be regulated by GDP
      dissociation inhibitors (GDI), three of which have been cloned thus far. Previous
      data suggest that Rab4 binds two of these isoforms of GDI (1 and 2) similarly
      when purified proteins are employed [Shisheva, A., et al. (1994) Mol. Cell. Biol.
      14, 3459-3468]. In the present study, we have analyzed the cytosolic Rab4 in
      complexes with GDI-1 or GDI-2 in intact cells using a coprecipitation technique.
      We show here that in insulin-sensitive 3T3-L1 adipocytes and other cultured
      cells, Rab4 simultaneously forms stable cytosolic complexes with both GDI-1 and
      GDI-2. Acute insulin treatment of the cultured adipocytes significantly increases
      cytosolic levels of Rab4 which can be quantitatively immunoprecipitated with anti
      Rab4 antibodies. Surprisingly, the increased cytosolic Rab4 due to insulin action
      is predominantly associated with cytosolic GDI-1. The levels of cytosolic Rab4
      GDI-2 complexes were virtually unaltered by insulin. Insulin-dependent
      alterations of Rab4 and GDI-1 phosphorylation were not detected in 32P-labeled
      3T3-L1 adipocytes, suggesting another mechanism accounts for the specificity of
      Rab4 binding to GDI-1. Taken together, these data suggest there is selective
      formation of Rab4-GDI-1 complexes in response to insulin which plays a role in
      the action of insulin on membrane trafficking.

PMID- 9184136
TI  - Influence of the local helical conformation on the guanine modifications
      generated from one-electron DNA oxidation.
AB  - Two major products, 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentafuranosyl)amino]
      5-(2H )-oxazolone and its imidazole derivative have been generated from one
      electron oxidation of the free 2'-deoxyguanosine. The formation of 7,8-dihydro-8
      oxoguanine (8-oxodG), not detected in this case, has been observed from DNA
      exposed to oxidizing agents. Since these compounds are thought to reflect,
      respectively, either deprotonation or hydration of the transient guanyl radical
      cation, these findings suggested that the helical structure could influence the
      chemical decomposition pathway of the guanine moiety. In the present study, we
      have photoionized DNA sequences by exposure to high-intensity UV (266 nm) laser
      pulses. Homo- or heteroduplexes, including guanines in various environments as
      well as Gn runs, were used as templates. Lesions were analyzed, at the nucleotide
      level, by taking advantage of the specific removal of 8-oxodG from DNA by the
      formamidopyrimidine DNA glycosylase (Fpg protein) and of the differential
      sensitivity of 8-oxodG and oxazolone to piperidine. Variations were observed in
      the relative yield of each type of lesion at individual guanines of the DNA
      sequences. We found that the Fpg lesions predominate in regions of stable double
      helix but are decreased in favor of the piperidine ones in regions of
      destabilization of the helix. Results are discussed in terms of a relationship
      between intramolecular rearrangements of the guanyl radical cation and the DNA
      helical conformation and dynamics.

PMID- 9184138
TI  - Structure-based thermodynamic analysis of HIV-1 protease inhibitors.
AB  - A structural parametrization of the binding and folding energetics previously
      developed in this laboratory accounts quantitatively for the binding of 13 HIV-1
      protease inhibitors for which high-resolution structures are available (A77003,
      A78791, A76928, A74704, A76889, VX478, SB203386, SB203238, SB206343, U100313,
      U89360, A98881, CGP53820). The binding free energies for the inhibitors are
      predicted with a standard deviation of +/- 1.1 kcal/mol or +/- 10%. Furthermore,
      the formalism correctly predicts the observed change in inhibition constant for
      the complex of A77003 and the resistant protease mutant V82A, for which the high
      resolution structure is also available. The analysis presented here provides a
      structural mapping of the different contributions to the binding energetics.
      Comparison of the binding map with the residue stability map indicates that the
      binding pocket in the protease molecule has a dual character: half of the binding
      site is defined by the most stable region of the protein, while the other half is
      unstructured prior to inhibitor or substrate binding. This characteristic of the
      binding site accentuates cooperative effects that permit mutations in distal
      residues to have a significant effect on binding affinity. These results permit
      an initial assessment of the effects of mutations on the activity of protease
      inhibitors.

PMID- 9184137
TI  - Resonance Raman examination of the wavelength regulation mechanism in human
      visual pigments.
AB  - Resonance Raman spectra of recombinant human green and red cone pigments have
      been obtained to examine the molecular mechanism of color recognition by visual
      pigments. Spectra were acquired using a 77 K resonance Raman microprobe or
      preresonance Raman spectroscopy. The vibrational bands were assigned by
      comparison to the spectra of bovine rhodopsin and model compounds. The C=NH
      stretching frequencies of rhodopsin, the green cone pigment, and the red cone
      pigment in H2O (D2O) are found at 1656 (1623), 1640 (1618), and 1644 cm(-1),
      respectively. Together with previous resonance Raman studies on iodopsin [Lin, S.
      W., Imamoto, Y., Fukada, Y., Shichida, Y., Yoshizawa, T., & Mathies, R. A. (1994)
      Biochemistry 33, 2151-2160], these values suggest that red and green pigments
      have very similar Schiff base environments, while the Schiff base group in
      rhodopsin is more strongly hydrogen-bonded to its protein environment. The
      absence of significant frequency and intensity differences of modes in the
      fingerprint and the hydrogen out-of-plane wagging regions for all these pigments
      does not support the hypothesis that local chromophore interactions with charged
      protein residues and/or chromophore planarization are crucial for the absorption
      differences among these pigments. However, our data are consistent with the idea
      that the Schiff base group in blue visual pigments is stabilized by protein and
      water dipoles and that the removal of this dipolar field shifts the absorption
      maximum from blue to green. A further red shift of the lambda(max) from the green
      to the red pigment is successfully modeled by the addition of hydroxyl-bearing
      amino acids (Ser164, Tyr261, and Thr269) close to the ionone ring that lower the
      transition energy by interacting with the change of dipole moment of the
      chromophore upon excitation. The increased hydrogen bonding of the protonated
      Schiff base group in rhodopsin is predicted to account for the 30 nm blue shift
      of its absorption maximum compared to that of the green pigment.

PMID- 9184139
TI  - The crystallographic structure of the subtilisin protease from Penicillium
      cyclopium.
AB  - The major extracellular protease from the fungus Pencillium cyclopium was
      crystallized in the presence of p-phenylmethanesulfonyl fluoride (PMSF) and
      investigated by X-ray diffraction analysis. It was subsequently cloned and the
      amino acid sequence deduced from its cDNA. Although the sequence is only 49%
      identical to that of proteinase K of Tritirachium album, the three-dimensional
      structures of the two proteases are virtually identical. The model for P.
      cyclopium protease was refined by simulated annealing to an R of 18% at 1.7 A
      resolution. The greatest variation from the proteinase K polypeptide is in loop
      114-134 and is due to the absence of a disulfide bridge in the P. cyclopium
      protease that is present in proteinase K. A difference was also observed in the
      orientation of the histidine in the catalytic triad, though this could be due to
      the presence of PMSF at the active site. The coordination geometry of the
      strongly bound calcium in the P. cyclopium protease is octahedral and uses some
      different protein ligands than does proteinase K. In the protease from P.
      cyclopium there is no cysteine near the active site, nor is there a second
      calcium binding site as is found in proteinase K, suggesting that neither is
      important to catalytic activity.

PMID- 9184140
TI  - Surface loops adjacent to the cation-binding site of the complement factor B von
      Willebrand factor type A module determine C3b binding specificity.
AB  - The interaction of factor B with C3b deposited on the surface of pathogens is the
      first step in the activation of the alternative complement pathway. The role of
      the von Willebrand factor type A (VWFA) module of factor B in this interaction
      has been investigated by generating three chimeras, Ch1-Ch3, in which surface
      loops of the VWFA module flanking the cation-binding residues were replaced by
      the corresponding sequences of C2, a factor B-like molecule which does not bind
      C3b. The location of the three loops was inferred from a homology model based on
      the structure of the integrin alphaM VWFA module [Ch1, betaA-alpha1 loop: Ch2,
      alpha3-alpha4 loop; and Ch3, betaD-alpha5 loop; Lee, J.-O., et al. (1995b) Cell
      80, 631-638]. The function of the chimeras was studied by means of hemolytic
      assays and assays of the individual steps of the alternative complement pathway,
      i.e., binding to the C3b analogue cobra venom factor and factor D cleavage. These
      experiments showed that Ch1 and Ch3 define regions that are involved in C3b
      binding whereas Ch2 does not appear to be involved in binding specificity. The
      inability of Ch1 to register the enhancement of cobra venom factor binding
      normally seen after factor D cleavage suggested that the betaA-alpha1 loop
      mediates the conformational regulation of ligand binding affinity. Homology
      modeling of the chimeras has been used to visualize the surface structures which
      potentially define the C3b binding site.

PMID- 9184141
TI  - 23S rRNA similarity from selection for peptidyl transferase mimicry.
AB  - RNAs from a randomized pool were selected by affinity elution for binding to the
      molecule CCdApPuro, a high-affinity ligand of ribosomal peptidyl transferase
      designed as a transition-state analogue of peptide formation. The selected RNAs
      show affinity for CCdApPuro comparable to that of the peptidyl transferase center
      itself (Kd approximately 10 nM). Chemical modification/protection experiments
      implicate bases completely conserved among the selected RNAs in CCdApPuro
      interaction, which appears to involve both CCdA and puromycin moieties, that is,
      both A- and P-site homologues. The apparent selected binding site shows up to 17
      nucleotides with similarity to conserved nucleotides of the peptidyl transferase
      loop domain of 23S rRNA and is conserved when reselected under mutagenesis. Thus,
      these nucleotides of 23S rRNA likely provide elements of the peptidyl transferase
      active center that bind the reactants near the site of peptide bond formation.
      Binding of CCdApPuro by a peptidyl transferase-like motif in the absence of
      protein strengthens the hypothesis that peptidyl transfer originated in an RNA
      world.

PMID- 9184142
TI  - Engineering hyperactive variants of human deoxyribonuclease I by altering its
      functional mechanism.
AB  - Human deoxyribonuclease I (DNase I), an enzyme used to treat cystic fibrosis
      patients, has been engineered to more effectively degrade double-stranded DNA to
      lower molecular weight fragments by altering its functional mechanism from the
      native single-stranded nicking pathway to a much more efficient one which results
      in increased double-stranded scission. By introducing positively charged amino
      acids at DNase I positions that can interact favorably with the proximal
      negatively charged phosphate groups of the DNA, we have created a hyperactive
      variant with approximately 35-fold higher DNA-degrading activity relative to wild
      type. This enhancement can be attributed to both a decrease in Km and an increase
      in Vmax. Furthermore, unlike wild-type DNase I, the hyperactive variants are no
      longer inhibited by physiological saline. Replacement of the same positions with
      negatively charged amino acids greatly reduced DNA cleavage activity, consistent
      with a repulsive effect with the neighboring DNA phosphates. In addition, these
      variants displayed similar activities toward a small synthetic substrate, p
      nitrophenyl phenylphosphonate, suggesting that the difference in DNA cleavage
      activity is due to the interaction of the engineered charged residues with the
      DNA phosphate backbone rather than any change in catalytic machinery. Finally,
      experiments involving the repair of DNase I digested DNA with T4 DNA ligase and
      the Klenow fragment of DNA polymerase I suggest that single-stranded gaps are
      introduced by the hyperactive variants. Thus, the increased functional activity
      of the hyperactive variants may be explained in part by a shift toward a
      processive DNA nicking mechanism, which leads to a higher frequency of double
      stranded breaks.

PMID- 9184143
TI  - Phosphatidylinositol-specific phospholipase C: kinetic and stereochemical
      evidence for an interaction between arginine-69 and the phosphate group of
      phosphatidylinositol.
AB  - A new substrate analogue, (2R)-1,2-dipalmitoyloxypropanethiophospho-1-D-myo
      inositol (DPsPI), has been used in a new, continuous assay for
      phosphatidylinositol-specific phospholipase C (PI-PLC). DPsPI is superior to
      other substrate analogs that have been used for assaying PI-PLC since it is
      synthesized as a pure diastereomer and maintains both acyl chains of the natural
      substrate, dipalmitoylphosphatidylinositol (DPPI). The assay that has been
      developed using this new analogue has allowed us to elucidate detailed kinetic
      data so far lacking in the field. In addition, several mutants of PI-PLC were
      constructed and assayed. The results show that Arg-69 is essential for catalysis,
      since mutations at this position led to a 10(3)- 10(4)-fold decrease in activity
      with respect that of to the wild-type (WT) enzyme. An alanine mutant of Asp-67, a
      residue also found at the active site, displays activity similar to that of WT.
      We have also used nuclear magnetic resonance (NMR) and circular dichroism (CD)
      spectroscopy to analyze the structural integrity and conformational stability of
      the mutants. The results show that the overall global conformation of the enzyme
      is not perturbed by the mutants. The 15N-1H HSQC NMR spectrum of WT PI-PLC is
      also reported at 600 MHz. The stereoselectivity of the reaction toward the
      stereoisomers of another analogue, 1,2-dipalmitoyl-sn-glycero-3-thiophospho-1-myo
      inositol (DPPsI), was used to probe whether Arg-69 interacts with the phosphate
      moiety of the substrate. We have calculated that the WT enzyme shows a
      stereoselectivity ratio of 160000:1 in favor of the Rp isomer versus the Sp
      isomer. The R69K mutant displayed a significant 10(4)-fold relaxation of
      stereoselectivity. Our data support the role of Arg-69 in stabilizing the
      negative charge on the pentacoordinate phosphate in the transition state during
      catalysis.

PMID- 9184144
TI  - Comparison of cholesterol and sitosterol uptake in different brush border
      membrane models.
AB  - (I) There is little discrimination between cholesterol and the plant sterol
      sitosterol in the uptake at the brush border membrane (BBM). (II) This difference
      cannot account for the marked discrimination between cholesterol and sitosterol
      observed in the absorption of these two sterols by the small-intestinal
      epithelium. (III) This discrimination occurs during intracellular processing
      involving the esterification and incorporation into lipoprotein particles of the
      two sterols. This conclusion is based on a comparative study of sterol uptake by
      brush border membrane vesicles (BBMV) and sterol absorption by Caco-2 cells. (IV)
      The uptake of sitosterol by the BBM is energy-independent and facilitated in a
      manner analogous to cholesterol uptake [Thurnhofer, H., & Hauser, H. (1990a)
      Biochemistry 29, 2142-2148]. (V) The rate of cholesterol and sitosterol uptake by
      BBMV from both mixed bile salt micelles and small unilamellar vesicles (SUV) as
      the donor is directly proportional to the sterol content of the donor. (VI) The
      pseudo-first-order rate constants k1 for sterol uptake from SUV are independent
      of the sterol content up to 10-20 mol %. Above that, competition between the two
      sterols leads to a reduction of the k1 values.

PMID- 9184145
TI  - Histidine-rich glycoprotein binds to human IgG and C1q and inhibits the formation
      of insoluble immune complexes.
AB  - Purification of the complement component C1q from human serum using an
      established method resulted in the copurification of two 30 kDa proteins with an
      N-terminal sequence identical to human histidine-rich glycoprotein (HRG).
      Therefore, to explore the possibility that HRG can interact with C1q, we examined
      the ability of 81 kDa (native) and the 30 kDa proteins (presumably proteolytic N
      terminal fragments of HRG) to bind to C1q, using both ELISA and optical biosensor
      techniques. Both forms of HRG were found to bind to the human complement
      component C1q and also to purified human and rabbit IgG by ELISA. Kinetic
      analyses of the HRG-C1q and HRG-IgG interactions using the IAsys biosensor
      indicate two distinct binding sites with affinities Kd1 0.78 x 10(-8) M and Kd2
      3.73 x 10(-8) M for C1q, and one binding site with affinity Kd 8.5 x 10(-8) M for
      IgG. Moreover, the fact that both native and 30 kDa HRG bind to C1q and to IgG
      suggests that the IgG and C1q binding regions on HRG are located in the 30 kDa N
      terminal region of the HRG molecule. The Fab region of IgG is likely to be
      involved in the HRG-IgG interaction since HRG also bound to F(ab')2 fragments
      with an affinity similar to that seen with the complete IgG molecule.
      Interestingly, the binding between HRG and IgG was significantly potentiated (Kd
      reduced from 85.0 to 18.9 nM) by the presence of physiological concentrations of
      Zn2+ (20 microM). Conversely, the presence of Zn2+ weakened the binding of HRG to
      C1q (Kd increased from 7.80 to 29.3 nM). Modulation of these interactions by
      other divalent metal cations was less effective with relative potencies being
      Zn2+ > Ni2+ > Cu2+. An examination of the effect of native and 30 kDa HRG on the
      formation of insoluble immune complexes (IIC) between ovalbumin and polyclonal
      rabbit anti-ovalbumin IgG revealed that physiological concentrations of HRG can
      markedly inhibit IIC formation in vitro. The results show that human HRG binds to
      C1q and to IgG in a Zn2+-modulated fashion, and that HRG can regulate the
      formation of IIC in vitro, thus indicating a new functional role for HRG in vivo.

PMID- 9184146
TI  - Contribution of surface histidyl residues in the alpha-chain to the Bohr effect
      of human normal adult hemoglobin: roles of global electrostatic effects.
AB  - We have applied site-directed mutagenesis to our Escherichia coli hemoglobin
      expression plasmid and constructed five recombinant mutant hemoglobins (r Hbs): r
      Hb(alpha20His-->Gln or alpha:H20Q); r Hb(alpha:H50Q); r Hb(alpha:H72Q); r
      Hb(alpha:H89Q); and r Hb(alpha:H112Q). We have constructed these r Hbs to help us
      assess the contribution of the surface histidyl residues in the alpha-chain to
      the alkaline Bohr effect of human normal adult hemoglobin (Hb A). In our
      laboratory, we have monitored the variation of proton nuclear magnetic resonances
      arising from the C2 protons of the histidyl residues of Hb A as a function of pH
      and buffer conditions. Several of these resonances have been assigned to the
      individual histidyl residues on the surface of the hemoglobin molecule using
      naturally occurring mutant hemoglobins and chemically modified hemoglobins. In
      the present work, we have identified the C2 proton resonances of five surface
      histidyl residues of the alpha-chain, alpha20, alpha50, alpha72, alpha89, and
      alpha112, in both the carbonmonoxy and deoxy forms, by comparing the proton
      nuclear magnetic resonance spectra of Hb A with those of the r Hbs. For the
      assignment of the C2 proton resonances of alpha20His and alpha112His, we have
      used combinations of mutations to compensate for the spectral perturbations
      resulting from the single mutations, which obscure the resonance assignment. On
      the basis of the new findings, in solvent containing 0.1 M chloride, the overall
      contributions from surface histidyl residues of both the alpha- and beta-chain
      and from other previously identified alkaline Bohr groups account for
      approximately 75% of the observed Bohr effect at pH 7.3 (the maximum Bohr effect
      under the prescribed solvent conditions). Our results show that some histidyl
      residues contribute to the Bohr effect and some oppose the net Bohr effect. In
      some cases, the addition of anions can diminish or reverse the contributions of
      specific histidyl residues to the overall Bohr effect. Thus, the Bohr effect, a
      heterotropic effect, depends on the intricate arrangement and interactions of all
      hydrogen and anion binding sites in the hemoglobin molecule. It is an excellent
      example of global electrostatic effects in proteins.

PMID- 9184147
TI  - Energetics of thrombin-thrombomodulin interaction.
AB  - Temperature and salt dependence studies of thrombin interaction with
      thrombomodulin, with and without chondroitin sulfate, and two fragments
      containing the EGF-like domains 4-5 and 4-5-6 reveal the energetic signatures and
      the mechanism of recognition of this physiologically important cofactor. Binding
      of thrombomodulin is affected drastically by the particular salt present in
      solution and is positively linked to Na+ binding to thrombin and the conversion
      of the enzyme from the slow to the fast form, but is opposed by Cl- binding to
      the fibrinogen recognition site and especially to the heparin binding site.
      Binding of thrombomodulin has an unusually large salt dependence (gamma(salt) = 
      4.8) contributed mostly by the polyelectrolyte-like nature of the chondroitin
      sulfate moiety that binds to the heparin binding site and increases the affinity
      of the cofactor by almost 10-fold. On the other hand, the chondroitin sulfate has
      no effect on the deltaCp of binding, which is determined predominantly by
      contacts made by the EGF-like domains 5 and 6 with the fibrinogen recognition
      site. The modest heat capacity change (-0.2 kcal mol(-1) K(-1)) observed when
      thrombomodulin binds to the fast form suggests a rigid-body association of the
      cofactor with the enzyme. In the slow form, however, the heat capacity change is
      significantly more pronounced (-0.5 kcal mol(-1) K(-1)) and signals the presence
      of a conformational transition of the enzyme linked to binding of the cofactor
      that mimics the slow-->fast conversion. These results demonstrate that
      recognition of thrombomodulin by thrombin is steered electrostatically by the
      highly charged regions of the fibrinogen recognition site and the heparin binding
      site, to which the chondroitin sulfate moiety binds and enhances the affinity of
      the interaction. The recognition event also involves conformational changes of
      the enzyme in the slow form mediated by binding of the EGF-like domains 5-6 to
      the fibrinogen recognition site. Consistent with this model, binding of
      thrombomodulin to the fast form has only a small effect on the hydrolysis of nine
      chromogenic substrates carrying substitutions at P1, P2, and P3 aimed at probing
      the environment of the specificity sites S1, S2, and S3 of the enzyme. Binding to
      the slow form, on the other hand, enhances the specificity toward all substrates
      up to 15-fold. For substrates carrying a Gly at P2, binding of thrombomodulin
      changes the relative specificity of the slow and fast forms and makes the slow
      form more specific. Interestingly, these effects are not specific of
      thrombomodulin and depend solely on binding to the fibrinogen recognition site of
      the enzyme. In fact, they are also observed with the hirudin C-terminal fragment
      55-65. The characterization of the mechanism of thrombin-thrombomodulin
      interaction and the effects of the cofactor on the hydrolysis of chromogenic
      substrates probing the interior of the catalytic pocket bear on the
      thrombomodulin-induced enhancement of protein C cleavage by thrombin. We propose
      that this enhancement is due predominantly to an effect of thrombomodulin on the
      bound protein C in the ternary complex. Therefore, thrombomodulin would carry out
      its physiological function by making protein C a better substrate for thrombin,
      rather than making thrombin a better enzyme for protein C.

PMID- 9184148
TI  - The oligosaccharide side chain on Asn-135 of alpha-antithrombin, absent in beta
      antithrombin, decreases the heparin affinity of the inhibitor by affecting the
      heparin-induced conformational change.
AB  - The beta-form of antithrombin, lacking a carbohydrate side chain on Asn-135, is
      known to bind heparin more tightly than the fully glycosylated alpha-form. The
      molecular basis for this difference in affinity was elucidated by rapid-kinetic
      studies of the binding of heparin and the antithrombin-binding heparin
      pentasaccharide to plasma and recombinant forms of alpha- and beta-antithrombin.
      The dissociation equilibrium constant for the first step of the two-step
      mechanism of binding of both heparin and pentasaccharide to alpha-antithrombin
      was only slightly higher than that for the binding to the beta-form. The
      oligosaccharide at Asn-135 thus at most moderately interferes with the initial,
      weak binding of heparin to alpha-antithrombin. In contrast, the rate constant for
      the conformational change induced by heparin and pentasaccharide in the second
      binding step was substantially lower for alpha-antithrombin than for beta
      antithrombin. Moreover, the rate constant for the reversal of this conformational
      change was appreciably higher for the alpha-form than for the beta-form. The
      carbohydrate side chain at Asn-135 thus reduces the heparin affinity of alpha
      antithrombin primarily by interfering with the heparin-induced conformational
      change. These and previous results suggest a model in which the Asn-135
      oligosaccharide of alpha-antithrombin is oriented away from the heparin binding
      site and does not interfere with the first step of heparin binding. This initial
      binding induces conformational changes involving extension of helix D into the
      adjacent region containing Asn-135, which are transmitted to the reactive-bond
      loop. The resulting decreased conformational flexibility of the Asn-135
      oligosaccharide and its close vicinity to the heparin binding site destabilize
      the activated relative to the native conformation. This effect results in a
      higher energy for inducing the activated conformation in alpha-antithrombin,
      leading to a decrease in heparin binding affinity.

PMID- 9184149
TI  - Leukocyte 12-lipoxygenase: expression, purification, and investigation of the
      role of methionine residues in turnover-dependent inactivation and 5,8,11,14
      eicosatetraynoic acid inhibition.
AB  - Porcine leukocyte 12-lipoxygenase cDNA was cloned into the expression vectors
      pSE280, pSE380, and pSE420. pSE380 yielded the highest level of 12-lipoxygenase
      activity when these vectors were tested for expression in Escherichia coli Top10
      cells. Optimal expression of the protein from this vector occurred in cells
      cultured at 30 degrees C and harvested 18 h following induction of expression by
      0.5 mM isopropyl thiogalactoside (IPTG). The enzyme was purified from the 100000
      g supernatant to 98% homogeneity by a combination of ammonium sulfate
      precipitation, anion exchange chromatography, and chromatofocusing. Addition of
      dithiothreitol and catalase to buffers at various steps in the purification
      protocol enabled the isolation of enzyme having a specific activity of 12
      micromol min(-1) mg(-1). The recovery of purified protein from this expression
      system was 56%, resulting in a 109-fold purification. On the basis of amino acid
      sequence comparisons between mammalian 15- and 12-lipoxygenases, three methionine
      residues in the porcine leukocyte 12-lipoxygenase (M338L, M367V, and M562L) were
      targeted for mutation to assess their potential role in turnover-dependent
      inactivation and inhibition by 5,8,11,14-eicosatetraynoic acid (ETYA). The
      mutants were expressed and purified by the same procedure used for the wild-type
      enzyme. These amino acid changes did not significantly alter enzyme catalysis as
      judged by the kinetic constants Km and k(cat)/Km, nor did they affect the rate of
      turnover-dependent inactivation or inhibition by ETYA. The results indicate that
      these methionine residues do not play a pivotal role in catalysis,
      autoinactivation, or sensitivity to inhibition by acetylenic compounds.

PMID- 9184150
TI  - Titration calorimetric analysis of AcylCoA recognition by myristoylCoA:protein N
      myristoyltransferase.
AB  - Saccharomyces cerevisiae myristoylCoA:protein N-myristoyltransferase (Nmt1p) is
      an essential enzyme that catalyzes the transfer of myristic acid (C14:0) from
      myristoylCoA to the N-terminus of cellular proteins with a variety of functions.
      Nmts from an assortment of species display remarkable in vivo specificity for
      this rare acyl chain. To better understand the mechanisms underlying this
      specificity, we have used isothermal titration calorimetry as well as kinetic
      measurements to study the interactions of Nmt1p with acylCoA analogs having
      variations in chain length and/or conformation, analogs with alterations in the
      thioester bond, and analogs with or without a 3'-phosphate in their CoA moiety.
      MyristoylCoA binds to Nmt1p with a Kd of 15 nM and a large exothermic deltaH (-25
      kcal/mol). CoA derivatives of C12:0-C16:0 fatty acids bind to Nmt1p with similar
      affinity, but with much smaller deltaH and a correspondingly less negative
      TdeltaS than myristoylCoA. Replacing the thioester carbonyl group with a
      methylene or removing the 3'-phosphate of CoA is each sufficient to prevent the
      low enthalpy binding observed with myristoylCoA. The carbonyl and the 3'
      phosphate have distinct and important roles in chain length recognition over the
      range C12-C16. Acyltransferase activity parallels binding enthalpy. The naturally
      occurring cis-5-tetradecenoylCoA and cis-5,8-tetradecadienoylCoA are used as
      alternative Nmt substrates in retinal photoreceptor cells, even though they do
      not exhibit in vitro kinetic or thermodynamic properties that are superior to
      those of myristoylCoA. The binding of an acylCoA is the first step in the
      enzyme's ordered reaction mechanism. Our findings suggest that within cells,
      limitation of Nmt substrate usage occurs through control of acylCoA availability.
      This indicates that full understanding of how protein acylation is controlled not
      only requires consideration of the acyltransferase and its peptide substrates but
      also consideration of the synthesis and/or presentation of its lipid substrates.

PMID- 9184151
TI  - Formyl phosphate: a proposed intermediate in the reaction catalyzed by
      Escherichia coli PurT GAR transformylase.
AB  - The Escherichia coli purT encoded glycinamide ribonucleotide transformylase (GAR
      transformylase) serves as an alternate enzyme in the production of formyl GAR for
      use in de novo purine biosynthesis. This enzyme differs from the previously known
      purN encoded enzyme in size, sequence, and substrates; ATP and formate are
      required as opposed to formyl tetrahydrofolate. Kinetic studies of the wild-type
      PurT enzyme described here demonstrate that formyl phosphate behaves as a
      chemically and kinetically competent intermediate. The requirement for ATP and
      GAR in these reactions is consistent with previous steady-state kinetic results,
      which demonstrated that all substrates must be bound before catalysis. Kinetic
      characterization of a mutant, which releases formyl phosphate into solution, and
      positional isotope exchange studies also support the assignment of formyl
      phosphate as a plausible intermediate.

PMID- 9184152
TI  - Identification of a partially rate-determining step in the catalytic mechanism of
      cAMP-dependent protein kinase: a transient kinetic study using stopped-flow
      fluorescence spectroscopy.
AB  - The kinetics of nucleotide binding and phosphoryl group transfer were measured in
      the catalytic subunit of cAMP-dependent protein kinase using stopped-flow
      fluorescence spectroscopy and an acrylodan-labeled derivative of this enzyme,
      which we have previously shown to have kinetic properties similar to those for
      the wild-type enzyme (Lew et al., 1996). The fluorescence emission spectrum of
      this enzyme is quenched differentially by ATP and ADP so that both the binding of
      ligands and phosphoryl group transfer at the active site can be monitored
      selectively. The association and dissociation rate constants for both nucleotides
      were measured using two methods: relaxation and competition binding. The ratio of
      the observed dissociation and association rate constants by both methods are
      consistent with Kd measurements (25 microM) determined by equilibrium
      fluorescence quenching. The dissociation rate constant for ADP (100 s(-1)) is
      approximately 2.5-fold larger than k(cat) (39 s(-1)). A full viscosity effect was
      measured for k(cat), suggesting that a diffusive step or steps limit maximum
      turnover. Pre-steady-state kinetic transients are biphasic and were fitted to
      observed rate constants of 500 s(-1) and 60 s(-1) at 500 microM Kemptide
      (LRRASLG). Metal substitution studies (Mg2+ vs Mn2+) indicate that this first
      phase represents the phosphoryl group transfer step. Phosphopeptide release is
      faster than this second phase since the substrate is in rapid exchange with the
      enzyme and phosphorylation reduces the affinity of the peptide. The inability to
      assign this second phase to the chemical event or to product release implies that
      it reflects a viscosity-sensitive, protein conformational change that occurs
      after phosphoryl group transfer and prior to product release. Two conformational
      steps were detected in the binding of both ATP and ADP by relaxation methods that
      may be related to this second pre-steady-state kinetic phase. We suggest that
      this additional step in the kinetic mechanism may also occur in the wild-type
      enzyme and represents a large structural change in the enzyme during normal
      catalytic cycling.

PMID- 9184153
TI  - Eucaryotic DNA primase does not prefer to synthesize primers at pyrimidine rich
      DNA sequences when nucleoside triphosphates are present at concentrations found
      in whole cells.
AB  - The critical role of NTP concentration in determining where calf thymus DNA
      primase synthesizes a primer on a DNA template was examined. Varying the
      concentration of NTPs dramatically altered the template sequences at which
      primase synthesized primers. At the low NTP concentrations typically used for in
      vitro experiments (100 microM), primase greatly preferred to synthesize primers
      at pyrimidine rich DNA sequences. However, when the concentrations of NTPs were
      increased to levels typically found in whole cells, primers were now synthesized
      in all regions of the template. Importantly, synthesis of primers in all regions
      of the DNA template, not just the pyrimidine rich sequences, is the pattern of
      primer synthesis observed during DNA replication in whole cells. With low
      concentrations of NTPs (i.e., Vmax/K(M) conditions), primers are only synthesized
      at the most preferred synthesis sites, namely, those that are pyrimidine rich. In
      contrast, under conditions of high NTP concentrations, primer synthesis will
      occur at the first potential synthesis site to which primase binds. Now, the
      primase x DNA complex will be immediately converted to a primase x DNA x NTP x
      NTP complex that is poised for primer synthesis.

PMID- 9184154
TI  - Functional domains of Escherichia coli single-stranded DNA binding protein as
      assessed by analyses of the deletion mutants.
AB  - A series of C- and N-terminal deletion mutants of Escherichia coli single
      stranded DNA binding protein (SSB) was constructed, purified, and characterized
      in terms of ability to self-multimerize and to bind to DNA. High-performance gel
      filtration chromatography revealed that the amino acids 89-105 play a key role in
      the maintenance of homotetramer for native SSB of 177 amino acids. Interestingly,
      all of the N-terminal deletion mutants studied here were eluted as octamers,
      indicating that the N-terminal 11 residues are involved in the prevention of the
      formation of octamers. The binding of SSB and its deletion mutant proteins to
      single-stranded d(T)n was examined by gel mobility shift assay and circular
      dichroism spectroscopy. C-terminal deletion mutant proteins, SSB1-135 and SSB1
      115, maintained high affinity and may be wrapped by single-stranded DNA (ssDNA)
      in the same way as in the case of native SSB. In contrast, deletion of the C
      terminal region (residues 89-115) or N-terminal region (residues 1-11) caused a
      dramatic decrease in the binding affinity. Furthermore, two different
      stoichiometries of SSB in the complexes with d(T)64, but not with d(T)32, were
      observed for native SSB, SSB1-135, SSB1-115, and SSB37-177, suggesting that the
      (SSB)65 and (SSB)35 binding modes, as previously demonstrated [Lohman, T. M., &
      Overman, L. B. (1985) J. Biol. Chem. 260, 3594-3603; Bujalowski, W., & Lohman, T.
      M. (1986) Biochemistry 25, 7799-7802], occurred at lower and higher SSB
      concentrations, respectively. A functional map for SSB molecule was presented and
      discussed.

PMID- 9184155
TI  - Zinc-dependent tRNA binding by a peptide element within a tRNA synthetase.
AB  - The class I aminoacyl-tRNA synthetases are defined by an N-terminal nucleotide
      binding fold that contains the active site for adenylate synthesis. Insertions
      and additions of idiosyncratic RNA binding elements that facilitate docking of
      the L-shaped tRNA structure are superimposed onto this basic fold. These RNA
      binding elements are imagined to have been acquired during the evolution and
      development of the modern genetic code. The monomeric Escherichia coli isoleucyl
      tRNA synthetase has a zinc-containing peptide at its C terminus. Removal of the
      zinc-containing peptide was shown previously to create a shortened enzyme with
      activity for adenylate synthesis but no detectable binding to tRNA(Ile). We show
      here that the isolated zinc-containing peptide binds to tRNA with relatively low
      affinity. This binding is not tRNA-specific but shows a strict requirement for
      zinc. In contrast, the zinc-containing peptide conferred specific and high
      affinity binding when combined with the shortened enzyme. Thus, when combined
      with another protein, a nonspecific tRNA binding peptide is essential for
      formation of a high-affinity and specific tRNA binding site. These results
      demonstrate the feasibility of the idea that noncovalent complexes of general RNA
      binding peptides with a domain for adenylate synthesis were precursors to modern
      tRNA synthetases. In addition, the results offer the first direct evidence of a
      role for zinc in the tRNA-binding activity of one of these peptide elements.

PMID- 9184156
TI  - Conformation of the N-terminal segment of a monocysteine mutant of troponin I
      from cardiac muscle.
AB  - A monocysteine mutant of cardiac muscle troponin I, cTnI(S5C/C81I/C98S), was
      generated from a mouse cTnI cDNA clone and expressed in a bacterial system. Cys-5
      was modified with the fluorescent sulfhydryl reagent IAANS to probe the
      conformation of the N-terminal extension of the mutant and the mutant complexed
      with cardiac muscle troponin C. Our emphasis was on the effect of phosphorylation
      of Ser-23 and Ser-24 by protein kinase A on the conformation of the N-terminal
      segment. Phosphorylation resulted in an 8-nm red-shift of the emission spectrum
      of the attached IAANS probe and a reduction of its quantum yield by a factor of 4
      5. The intensity decay of nonphosphorylated IAANS-labeled mutant was complex and
      had to be described by a sum of three exponential terms, with lifetimes in the
      range 0.1-5 ns. A fourth component in the range 7-9 ns was required to describe
      the intensity decay of the phosphorylated mutant. Phosphorylation also reduced
      the weighted mean lifetime, consistent with the changes observed in the steady
      state fluorescence parameters and a 33% decrease in the global rotational
      correlation time calculated from anisotropy decay data. This change in
      correlation time suggested a decrease in the axial ratio of the protein. The
      fluorescence changes of the labeled mutant induced by phosphorylation were
      carried over to its complex with troponin C. The Stern-Volmer plots of acrylamide
      quenching of the steady-state fluorescence were essentially linear for
      nonphosphorylated mutant but displayed pronounced concave downward curvatures for
      the phosphorylated protein under all conditions studied. The present results are
      interpreted in terms of a more compact hydrodynamic shape of the phosphorylated
      cTnI mutant and are consistent with a folded conformation of the N-terminal
      extension induced by phosphorylation of the two serines. These conformational
      changes may play a role in the modulation of cardiac muscle contractility by
      troponin I phosphorylation.

PMID- 9184157
TI  - Phosphorylation-induced distance change in a cardiac muscle troponin I mutant.
AB  - Phosphorylation of two adjacent serine residues in the unique N-terminal
      extension of cardiac muscle troponin I (cTnI) is known to decrease the Ca2+
      sensitivity of cardiac myofilaments. To probe the structural significance of the
      N-terminal extension, we have constructed two cTnI mutants each containing a
      single cysteine: (1) a full-length cTnI mutant (S5C/C81I/C98S) and (2) a
      truncated cTnI mutant (S9C/C50I/C67S) in which the N-terminal 32 amino acid
      residues were deleted. We determined the apparent binding constants for the
      complex formation between IAANS-labeled cardiac troponin C (cTnC) and the two
      cTnI mutants. The affinities of the cTnC for the truncated cTnI mutant were: (1)
      1.5 x 10(6) M(-1) in EGTA, (2) 28.9 x 10(6) M(-1) in Mg2+, and (3) 87.5 x 10(6)
      M(-1) in Mg2+ + Ca2+. These binding constants were approximately 1.4-fold smaller
      than the corresponding values obtained with the full-length cTnI mutant,
      suggesting a very small contribution of the N-terminal extension to the binding
      of cTnI to cTnC. Cys-5 in the full-length cTnI mutant was labeled with IAANS, and
      the distribution of the separation between this site and Trp-192 was determined
      by analysis of the efficiency of fluorescence resonance energy transfer from Trp
      192 to IAANS. The following mean distances were obtained with the
      unphosphorylated full-length mutant: 44.4 A (cTnI alone), 48.3 A (cTnI + cTnC),
      46.3 A (cTnI + cTnC in Mg2+), and 51.6 A (cTnI + cTnC in Mg2+ + Ca2+). The
      corresponding values of the mean distance determined with the phosphorylated full
      length cTnI mutant were 35.8, 36.6, 34.8, and 37.3 A. The phosphorylation of cTnI
      reduced the half-width of the distribution from 9.5 to 3.7 A. Similar but less
      pronounced decreases of the half-widths were also observed with the
      phosphorylated cTnI complexed with cTnC in different ionic conditions. Thus,
      phosphorylation of cTnI resulted in a decrease of 9-12 A in the mean distance
      between the sites located at the N- and C-terminal portion of cTnI. Our results
      indicate that phosphorylation elicits a change in the conformation of cTnI which
      underlies the basis of the phosphorylation-induced modulation of cTnI activity.

PMID- 9184158
TI  - MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable.
AB  - Muscle development is controlled by the MyoD family of basic helix-loop-helix
      (bHLH) DNA-binding proteins. These proteins dimerize with ubiquitous products of
      the E2A gene (E12 and E47) and bind in a sequence-specific manner to enhancer
      regions of muscle-specific genes activating their expression. In this study,
      fluorescence anisotropy has been utilized to characterize the interactions of
      recombinant MyoD and E12 in solution in the absence of DNA. The Gibb's free
      energies of dissociation (deltaG) and the equilibrium dissociation constants
      (K(D)) for the protein-protein interactions are reported. The deltaG for the MyoD
      homodimers in 100 mM KCl was 8.7 kcal/mol (K(D) = 340 nM), and increasing the
      salt concentration resulted in destabilization of the dimer. From titrations of
      MyoD-dansyl with E12 at 100 mM KCl, a free energy of heterodimerization of 8.7
      (+0.4/-2.4) kcal/mol was recovered using rigorous confidence limit testing. The
      titrations of E12-dansyl with MyoD yielded a free energy of 8.3 kcal/mol with
      tighter confidence limits, +0.5/-0.8 kcal/mol. Thus, in the absence of DNA, both
      MyoD homodimers and MyoD-E12 heterodimers are relatively weak complexes of
      approximately the same stability. E12 does not form stable homo-oligomeric
      complexes; remaining monomeric at concentrations as high as 20 microM. Based on
      these results and the apparent binding constants reported previously for DNA
      binding, DNA is likely to facilitate the dimerization of MyoD and E12.
      Furthermore, higher affinity interactions of MyoD-E12 heterodimers versus MyoD
      homodimers with DNA binding sites is not due to preferential heterodimerization.

PMID- 9184159
TI  - Oxidative damage does not alter membrane phospholipid asymmetry in human
      erythrocytes.
AB  - Oxidant-induced damage has been proposed to be the underlying mechanism for loss
      of membrane phospholipid asymmetry in the erythrocyte membrane. In sickle cell
      disease, thalassemia, and diabetes as well as in senescent erythrocytes, an
      apparent correlation between oxidative damage and loss of phosphatidylserine
      asymmetry has been reported. In the present study, erythrocytes were subjected to
      various levels of oxidative stress and/or sulfhydryl modifying agents. The
      transmembrane location of phosphatidylserine (PS) was assessed by FITC-conjugated
      annexin V labeling and the PS-dependent prothrombinase assay. Transbilayer
      movement of spin-labeled PS was used to determine aminophospholipid translocase
      activity. Our data show that cells did not expose PS as the result of oxidative
      stress induced by phenylhydrazine, hydrogen peroxide, tert-butyl hydroperoxide,
      cumene hydroperoxide, or sulfhydryl modification by N-ethylmaleimide (NEM) and
      diamide, even under conditions that led to severe cellular damage and impairment
      of aminophospholipid translocase activity. In contrast, the increase of
      intracellular calcium induced by treatment with calcium and ionophore A23187
      leads to a rapid scrambling of the lipid bilayer and the exposure of PS, which
      can be exacerbated by the inhibition of aminophospholipid translocase activity.
      Oxidation of the cells with hydrogen peroxide or phenylhydrazine did not affect
      A23187-induced uptake of calcium, but partly inhibited calcium-induced membrane
      scrambling. In conclusion, oxidative damage of erythrocytes does not induce
      exposure of phosphatidylserine on the membrane surface, but can interfere with
      both aminophospholipid translocase activity and calcium-induced randomization of
      membrane phospholipids.

PMID- 9184160
TI  - Membrane topology of the di- and tripeptide transport protein of Lactococcus
      lactis.
AB  - Transport of hydrophilic di- and tripeptides into Lactococcus lactis is mediated
      by a proton motive force-driven peptide transport protein (DtpT) that shares
      similarity with eukaryotic peptide transporters, e.g., from kidney and small
      intestine of rabbit, man, and rat. Hydropathy profiling in combination with the
      "positive inside rule" predicts for most of the homologous proteins an alpha
      helical bundle of 12 transmembrane segments, but the positions of these
      transmembrane segments and the location of the amino and carboxyl termini are by
      no means conclusive. The secondary structure of DtpT was investigated by
      analyzing 42 DtpT-alkaline phosphatase fusion proteins, generated by random or
      directed fusions of the corresponding genes. These studies confirm the presence
      of 12 transmembrane segments but refute several other predictions made of the
      secondary structure. Data obtained from the fusion proteins were substantiated by
      studying the accessibility of single cysteine mutants in putative cytoplasmic or
      extracellular loops by membrane (im)permeant sulfhydryl reagents. The deduced
      topology model of DtpT consists of a bundle of 12 alpha-helixes with a short
      amino and a large carboxyl terminus, both located at the cytoplasmic site of the
      membrane. On the basis of sequence comparisons with DtpT, it seems likely that
      the structure model of the amino-terminal half of DtpT also holds for the
      eukaryotic peptide transporters, whereas the carboxyl-terminal half is largely
      different.

PMID- 9184161
TI  - Chromophore formation in green fluorescent protein.
AB  - The green fluorescent protein (GFP) from the jellyfish Aequorea Victoria forms an
      intrinsic chromophore through cyclization and oxidation of an internal tripeptide
      motif [Prasher, D. C., et al. (1992) Gene 111, 229-233; Cody, C. E., et al.
      (1993) Biochemistry 32, 1212-1218]. We monitored the formation of the chromophore
      in vitro using the S65T-GFP chromophore mutant. S65T-GFP recovered from inclusion
      bodies in Escherichia coli lacks the mature chromophore, suggesting that protein
      destined for inclusion bodies aggregated prior to productive folding. This
      material was used to follow the steps leading to chromophore formation. The
      process of chromophore formation in S65T-GFP was determined to be an ordered
      reaction consisting of three distinct kinetic steps. Protein folding occurs
      fairly slowly (k(f) = 2.44 x 10(-3) s(-1)) and prior to any chromophore
      modification. Next, an intermediate step occurs that includes, but is not
      necessarily limited to, cyclization of the tripeptide chromophore motif (k(c) =
      3.8 x 10(-3) s(-1)). The final and slow step (k(ox) = 1.51 x 10(-4) s(-1)) in
      chromophore formation involves oxidation of the cyclized chromophore. Since the
      chromophore forms de novo from purified denatured protein and is a first-order
      process, we conclude that GFP chromophore formation is an autocatalytic process.

PMID- 9184162
TI  - Metal-ion-mediated allosteric triggering of yeast pyruvate kinase. 1. A
      multidimensional kinetic linked-function analysis.
AB  - Regulation of the glycolytic pathway is considered to be primarily achieved by
      the carbon metabolites resulting from glucose metabolism [e.g., fructose 1,6
      diphosphate (FDP), phosphoenolpyruvate (PEP), and citrate] and by the ATP charge
      of the cell. The divalent cations (e.g., Mg2+ and Mn2+) have not been considered
      as having regulatory roles in glycolysis, although they are involved in almost
      every enzyme-catalyzed reaction in the pathway. Using a kinetic linked-function
      analysis of steady-state kinetic data for the interactions of PEP, FDP, and Mn2+
      with yeast pyruvate kinase (YPK), we have found that the divalent metal is the
      principal trigger of the allosteric responses observed with this enzyme. The
      interaction of Mn2+ to YPK enhances the interaction of FDP by -1.6 kcal/mol and
      the interaction of PEP by -2.8 kcal/mol. The simultaneous interaction of all
      three of these ligands to YPK is favored by -4.3 kcal/mol over the sum of their
      independent binding free energies. Surprisingly, the binding of the allosteric
      activator FDP does not directly influence the binding of the substrate PEP since
      a coupling free energy near zero was calculated for these two ligands. Thus,
      communication between the PEP and FDP sites occurs structurally through the metal
      by an allosteric relay mechanism. These conclusions are supported by results of a
      thermodynamic linked-function analysis of direct binding data for the
      interactions of PEP, FDP, and Mn2+ with YPK [Mesecar, A. D., & Nowak, T. (1997)
      Biochemistry (following paper in this series)]. Our findings raise important
      questions as to the possible roles of divalent metals in modulating multiligand
      interactions with YPK and in the regulation of the glycolytic pathway.

PMID- 9184163
TI  - Metal-ion-mediated allosteric triggering of yeast pyruvate kinase. 2. A
      multidimensional thermodynamic linked-function analysis.
AB  - A role has been proposed for the free divalent metal in triggering the allosteric
      responses of yeast pyruvate kinase based upon a kinetic linked-function analysis
      [Mesecar, A. D., & Nowak, T. (1997a) (preceding paper in this series)]. The major
      conclusion from the analysis is that the allosteric activator, fructose 1,6
      diphosphate (FDP), does not directly communicate with the substrate,
      phosphoenolpyruvate (PEP), at the active site of the enzyme: it is Mn2+ that
      mediates the allosteric communication between the PEP and FDP sites in an
      allosteric relay mechanism. Assumptions were necessary to treat kinetic
      parameters as thermodynamic parameters, and the presence of the substrate ADP was
      necessary for the kinetic analysis. In this study, the influence of FDP on the
      interactions of PEP and Mn2+ and the influence of PEP and Mn2+ on the interaction
      of FDP with YPK were measured, where possible, by direct binding methods in the
      absence of ADP. Direct binding data were then subjected to a thermodynamic linked
      function analysis for a heterotropic, three ligand coupled system in order to
      ascertain the two and three ligand coupling free energies. The two ligand
      coupling free energies deltaG(Mn-PEP), deltaG(Mn-FDP), and deltaG(PEP-FDP) are 
      3.88, -1.09, and -0.22 kcal/mol, respectively. These values indicate that
      positive, heterotropic interactions exist between each of these ligand pairs. The
      three ligand coupling free energy term, deltaG(Mn-PEP-FDP), indicates that
      simultaneous binding of Mn2+, PEP, and FDP is considerably favored over the sum
      of their independent binding free energies by -6.6 kcal/mol. These results
      demonstrate the key role of the metal in the modulation of ligand binding and are
      consistent with the values and the relationships of the kinetic parameters
      obtained from the kinetic linked-function analysis.

PMID- 9184164
TI  - Kinetics of nitric oxide dissociation from five- and six-coordinate nitrosyl
      hemes and heme proteins, including soluble guanylate cyclase.
AB  - Kinetics of NO dissociation were characterized for three five-coordinate systems,
      heme-NO, HSA-heme-NO (human serum albumin), GC-NO (soluble guanylate cyclase),
      and for the six-coordinate system, Im-heme-NO. Nitrosyl myoglobin was
      redetermined for comparison. Previously known, six-coordinate R and T state
      nitrosyl hemoglobins are also included in the comparison. The data indicate that
      NO dissociates more than 1000 times faster from five-coordinate model heme than
      it does from the six-coordinate analog. Such a negative trans-effect between NO
      and a proximal base is in sharp contrast to carboxy heme derivatives, in which
      ligand dissociation rates are greatly slowed in when a trans base is present. As
      a result of opposite trans-effects, six-coordinate carboxy and nitrosyl
      derivatives have comparable dissociation rates, even though the five-coordinate
      species are very different. In proteins, five- and six-coordinate forms do not
      show a large difference in dissociation rates. Part of the reason may be due to
      different probabilities for geminate recombination in the different proteins, but
      this cannot explain all the facts. There must also be influences of the protein
      structure on bond-breaking rate constants themselves. With the exception of
      hemoglobin in the T state, nitrosyl guanylate cyclase shows the highest NO
      dissociation rate constant, k(obs) = 6 x 10(-4) s(-1). This would yield a half
      life of about 2 min at 37 degrees C for dissociation of NO from GC-NO, a number
      that has implications for the mechanism of regulation of the activity of this key
      heme enzyme.

PMID- 9184165
TI  - Refolding and reconstitution studies on the transacetylase-protein X (E2/X)
      subcomplex of the mammalian pyruvate dehydrogenase complex: evidence for specific
      binding of the dihydrolipoamide dehydrogenase component to sites on reassembled
      E2.
AB  - Reconstitution studies have been conducted on the dihydrolipoamide
      acetyltransferase-protein X core subcomplex of the mammalian pyruvate
      dehydrogenase complex. GdnHCl-induced dissociation of this core is an ordered
      cooperative event involving formation of specific lower-Mr intermediates
      corresponding to dihydrolipoamide acetyltransferase trimers and monomers.
      Recovery profiles of the dihydrolipoamide acetyltransferase-protein X core,
      unfolded in 6 M GdnHCl prior to the removal of denaturant by either (a) slow
      dialysis or (b) rapid dilution, demonstrated rapid initial reappearance of
      substantial levels of dihydrolipoamide acetyltransferase activity with complete
      recovery occurring in 4-6 h. Immunological analysis of reconstituted cores
      revealed reduced levels of protein X (approximately 30-35%) after slow dialysis
      and the total absence of this component following rapid dilution. The
      dihydrolipoamide acetyltransferase core, devoid of protein X, was unable to
      sustain overall complex activity when reconstituted with stoichiometric amounts
      of its companion pyruvate decarboxylase and dihydrolipoamide deydrogenase
      components, whereas the protein X-depleted core could sustain 30-35% of control
      activity. Further reconstitution analyses of overall complex function with these
      two types of reassembled core structures in the presence of excess
      dihydrolipoamide dehydrogenase (100-fold) demonstrated significant additional
      stimulation of pyruvate dehydrogenase complex activity (25-30%) which was
      dependent on the source of exogenous dihydrolipoamide dehydrogenase. Thus, this
      constituent enzyme can interact directly with the dihydrolipoamide
      acetyltransferase oligomer with low affinity in addition to its normal high
      affinity binding to the protein X subunit. These results provide definitive in
      vitro evidence in support of recent clinical observations reporting residual
      pyruvate dehydrogenase activity (10-20%) in cell lines derived from patients
      lacking protein X.

PMID- 9184166
TI  - Differential phosphorylation of pp120 by insulin and insulin-like growth factor-1
      receptors: role for the C-terminal domain of the beta-subunit.
AB  - pp 120, a plasma membrane glycoprotein expressed by hepatocytes, is a substrate
      of the insulin receptor tyrosine kinase. Since insulin-like growth factor-1 (IGF
      1) and insulin receptors are structurally homologous, we investigated whether
      pp120 is also a substrate of the IGF-1 receptor tyrosine kinase. IGF-1 receptor
      failed to phosphorylate pp120 in response to IGF-1 in stably transfected NIH 3T3
      fibroblasts. However, replacement of the C-terminal domain of the beta-subunit of
      the IGF-1 receptor with the corresponding fragment in the insulin receptor
      restored ligand-stimulated pp120 phosphorylation, suggesting that this domain
      plays a regulatory role in pp120 phosphorylation. Since pp120 is the first
      identified substrate specific for the insulin vis-a-vis the IGF-1 receptor
      tyrosine kinase, the pp120 signaling pathway may constitute a novel mechanism for
      the distinct cellular effects of insulin and IGF-1, the former being principally
      involved in metabolism, and the latter in mitogenesis.

PMID- 9184167
TI  - Purification and light-dependent phosphorylation of a candidate fusion protein,
      the photoreceptor cell peripherin/rds.
AB  - The proteins peripherin/rds and rom-1 form a protein complex in the rims of
      photoreceptor outer segment disk membranes. Peripherin/rds plays an essential
      role in the morphogenesis and maintenance of disk membrane structure, with
      peripherin/rds gene mutations resulting in photoreceptor cell degeneration. We
      report two different chromatographic procedures for the purification of native
      peripherin/rds from bovine photoreceptor cell outer segments and show that the
      protein is a phosphoprotein that promotes membrane fusion in vitro. During one
      procedure, peripherin/rds was copurified in association with rom-1 by
      hyroxylapatite and Mono Q FPLC. During the other, it was purified free from rom-1
      by concanavalin-A affinity chromatography and chromatofocusing. Analysis of
      homogeneous peripherin/rds from the second procedure showed that exposure of
      photoreceptor outer segments to light resulted in the incorporation of nearly 2
      mol of phosphate per mole of peripherin/rds and a concomitant shift in the
      isoelectric point of the protein. In addition, we found that recombination of
      purified peripherin/rds into lipid vesicles increased membrane fusion, with more
      rapid fusion detected with phosphorylated peripherin/rds. In conclusion, studies
      with purified peripherin/rds reveal that the protein undergoes light-dependent
      phosphorylation and that it may function in membrane fusion.

PMID- 9184168
TI  - Inhibition of P-glycoprotein ATPase activity by beryllium fluoride.
AB  - ATPase activity of P-glycoprotein (multidrug-resistance protein) was found to be
      potently inhibited by beryllium fluoride (BeFx) in combination with MgATP, MgADP,
      or corresponding Mg-8-azido-nucleotides. Inhibition was due to trapping of
      nucleoside diphosphate at catalytic sites. Full inhibition was achieved on
      trapping of 1 mol of nucleotide per mol of Pgp. Reactivation was slow (t(1/2) =
      32 min at 37 degrees C), and release of trapped nucleotide correlated with
      recovery of ATPase. Trapping of 8-azido-ADP followed by UV irradiation yielded
      permanent inactivation and specific labeling of Pgp in plasma membranes. Both N-
      and C-terminal nucleotide binding sites were labeled. These findings give strong
      confirmation of the concepts that in intact Pgp both nucleotide sites are active
      in MgATP hydrolysis, and that they interact strongly. The characteristics of
      inhibition by BeFx were similar in general to those seen with vanadate. However,
      PPi gave strong protection against BeFx inhibition, and in this respect,
      inhibition by BeFx was clearly different from vanadate inhibition.

PMID- 9184169
TI  - Inhibition of growth and induction of differentiation of metastatic melanoma
      cells in vitro by genistein: chemosensitivity is regulated by cellular p53.
AB  - We have investigated the effect of the soybean isoflavone genistein on the growth
      and differentiation of human melanoma cells. Four human melanoma cell lines,
      either completely lacking or containing different levels of wild-type p53, were
      treated with genistein in vitro in culture. It has been found that genistein
      significantly inhibited cell growth and that the chemosensitivity might depend on
      cellular p53 content. Specifically, the data suggest that high levels of wild
      type p53 expression make cells resistant to genistein's growth-inhibitory action.
      Further support for this observation came from the stable transfection studies in
      which p53 transfectants expressing high levels of wild-type p53 became resistant
      to genistein. With respect to cell differentiation, our study showed that
      genistein increased melanin content and tyrosinase activity and caused the cells
      to form dendrite-like structures. Cells lacking p53 responded more than cells
      with p53 to dendrite-like structure formation. We also observed that genistein
      induced differentiation involved an increase in tyrosinase mRNA level; the
      mechanisms by which genistein increases tyrosinase transcripts remain to be
      elucidated. Genistein treatment of the melanoma cell lines resulted in cell cycle
      arrest at G2/M check point and no significant apoptosis was observed.

PMID- 9184170
TI  - Expression of keratinocyte growth factor and its receptor in human breast cancer.
AB  - The level of expression of keratinocyte growth factor (KGF) mRNA has been
      measured in human breast cell lines, purified populations of epithelial cells,
      myoepithelial cells and fibroblasts from reduction mammoplasty tissue and a panel
      of 42 breast cancers and 30 non-malignant human breast tissues using a
      semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR)
      procedure. We found similar levels of KGF mRNA in malignant and non-malignant
      breast tissues. The study of the amount of KGF mRNA in breast cell lines and
      purified populations of cells revealed that fibroblasts are the predominant
      source of KGF with malignant and non-malignant epithelial cells containing very
      low levels of KGF mRNA. We have examined the distribution of fibroblast growth
      factor receptor (FGFR)-2-IIIb, which is a high-affinity receptor for KGF and find
      that it is present on malignant and non-malignant epithelial cells. The level of
      FGFR-2-IIIb present on breast cancer cell lines was sufficient for KGF
      stimulation of breast cancer cell proliferation. Other members of the fibroblast
      growth factor family have been either not expressed in the human breast (FGF3,
      FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and
      this is the first member of the family to potentially influence the progression
      of breast cancer through stimulation of cell division.

PMID- 9184173
TI  - Enhancement of paclitaxel activity against hormone-refractory prostate cancer
      cells in vitro and in vivo by quinacrine.
AB  - Cytoplasmic phospholipase A2 (PLA2) is known to be phosphorylated and activated
      by MAP kinase (Lin et al 1993, Cell 72: 269-278), an important downstream
      component of signal transduction, whereas paclitaxel has been shown to inhibit
      isoprenylation of ras proteins (Danesi et al 1995, Mol Pharmacol 47: 1106-1111).
      Given that quinacrine (Q), a PLA2 inhibitor, and paclitaxel (P) might act at
      different sites in the cell signalling pathway, our aim was to test whether they
      were synergistic in combination against prostate cancer cells. Cell viability of
      PC-3, PC-3M and DU145 cells in 96 - well plates was assessed 96 h after drugs
      were added concurrently. Using Chou analysis, we demonstrated synergy for the
      combination against all three cell lines. Further, synergy was present under both
      conservative (mutually non-exclusive) and non-conservative (mutually exclusive)
      models. Studies in the nude mouse xenograft model support the finding of synergy
      in vitro. In DU145-bearing mice, Q (50 mg kg(-1)) and P (0.5 mg kg(-1)) given
      daily for 12 consecutive days, either concurrently or sequentially, was more
      effective than either drug alone, at twice the dose intensity. In an enzyme
      linked immunosorbent (ELISA) apoptosis assay, arachidonic acid was able to
      partially reverse Q- and P-induced apoptosis, suggesting PLA2 pathway
      involvement. Finally, the combination of lovastatin, another inhibitor of ras
      isoprenylation, and quinacrine had synergistic inhibitory effects on the growth
      of PC-3 cells in vitro, suggesting that the combination of these two classes of
      compounds might serve as an attractive therapeutic approach for prostate cancer.

PMID- 9184172
TI  - Inhibition of in vivo proliferation of androgen-independent prostate cancers by
      an antagonist of growth hormone-releasing hormone.
AB  - Tumour-inhibitory effects of a new antagonist of growth hormone-releasing hormone
      (GH-RH), MZ-4-71, were evaluated in nude mice bearing androgen-independent human
      prostate cancer cell lines DU-145 and PC-3 and in Copenhagen rats implanted with
      Dunning R-3327 AT-1 prostatic adenocarcinoma. After 6 weeks of therapy, the
      tumour volume in nude mice with DU-145 prostate cancers treated with 40 microg
      day(-1) MZ-4-71 was significantly decreased to 37 +/- 13 mm3 (P < 0.01) compared
      with controls that measured 194 +/- 35 mm3. A similar inhibition of tumour growth
      was obtained in nude mice bearing PC-3 cancers, in which the treatment with MZ-4
      71 for 4 weeks diminished the tumour volume to 119 +/- 35 mm3 compared with 397
      +/- 115 mm3 for control animals. Therapy with MZ-4-71 also significantly
      decreased weights of PC-3 and DU-145 tumours and increased tumour doubling time.
      Serum levels of GH and IGF-I were significantly decreased in animals treated with
      GH-RH antagonist. In PC-3 tumour tissue, the levels of IGF-I and IGF-II were
      reduced to non-detectable values after therapy with MZ-4-71. The growth of
      Dunning R-3327 AT-1 tumours in rats was also significantly inhibited after 3
      weeks of treatment with 100 microg of MZ-4-71 day(-1) i.p. as shown by a
      reduction in tumour volume and weight (both P-values < 0.05). Specific high
      affinity binding sites for IGF-I were found on the membranes of DU-145, PC-3 and
      Dunning R-3327 AT-1 tumours. Our results indicate that GH-RH antagonist MZ-4-71
      suppresses growth of PC-3, DU-145 and Dunning AT-1 androgen-independent prostate
      cancers, through diminution of GH release and the resulting decrease in the
      secretion of hepatic IGF-I, or through mechanisms involving a lowering of tumour
      IGF-I levels and possibly an inhibition of tumour IGF-I and IGF-II production. GH
      RH antagonists could be considered for further development for the therapy of
      prostate cancer, especially after the relapse.

PMID- 9184171
TI  - Construction and functional characterization of scFv(14E1)-ETA - a novel, highly
      potent antibody-toxin specific for the EGF receptor.
AB  - Epidermal growth factor (EGF) receptor-overexpression is characteristic of many
      human tumours of epithelial origin and has been correlated with unfavourable
      patient prognosis. Its involvement in the malignant process, its elevated
      expression in tumours and its accessibility on the tumour cell surface make the
      EGF receptor a potential target for directed tumour therapy. We have previously
      characterized a recombinant antibody - Pseudomonas exotoxin A fusion protein,
      scFv(225)-ETA, which displayes antitumoral activity towards EGF receptor
      overexpressing tumour cells but is less potent in tumour cell killing than TGF
      alpha-ETA, a recombinant toxin using the natural EGF receptor ligand transforming
      growth factor alpha (TGF-alpha) as a targeting domain. Here, we describe the
      construction and functional characterization in vitro of a novel single-chain
      antibody-toxin, scFv(14E1)-ETA, based on the independently isolated EGF receptor
      specific monoclonal antibody 14E1. ScFv(14E1)-ETA binds to an EGF receptor
      epitope that is very similar or identical to that of scFv(225)-ETA with nine
      times higher affinity than the latter and displays more than tenfold higher
      cytotoxic activity on EGF receptor-overexpressing tumour cells. ScFv(14E1)-ETA
      cell killing activity was very similar to that of TGF-alpha-ETA on receptor
      overexpressing cells but, in contrast to the latter, scFv(14E1)-ETA was much more
      selective and did not display significant cytotoxic activity on cells expressing
      moderate EGF receptor levels.

PMID- 9184174
TI  - Dissociation of bone formation markers in bone metastasis of prostate cancer.
AB  - To clarify the meaning and clinical value of bone formation markers in bone
      metastasis from prostate cancer, we investigated the bone formation markers
      carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline
      phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43
      prostate cancer patients with and 46 patients without overt bone metastasis.
      Patients with bone metastasis were evaluated repeatedly by bone scan at intervals
      of 3-6 months. The expression patterns of bone formation markers in patients with
      progression of bone metastasis became dissociated; BA1-p and PICP were elevated
      in patients with progression of bone metastasis but BGP was not. Instead, BGP
      showed slight elevation in patients with improvement and complete remission of
      bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each
      marker appears in a different phase of bone formation: PICP appears in
      proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in
      late bone formation phase. Our findings that BGP was not elevated in progression
      of bone metastasis and that it increased slightly with improvement and complete
      remission of bone metastasis may imply that the bone formation that occurs in
      blastic bone metastasis is different from normal bone formation.

PMID- 9184176
TI  - Augmentation of production of TNF-alpha and anti-tumour activity by an
      amphotericin B preparation for clinical use in mice.
AB  - Effects of amphotericin B on production of endogenous tumour necrosis factor
      alpha (TNF-alpha) and anti-tumour activity in mice was examined. Intravenous
      administration of Fungizone, an amphotericin B preparation complexed with
      deoxycholate, augmented the induction of endogenous TNF in response to a second
      stimulus with intravenous doses of FK23 (heat-killed Enterococcus faecalis). This
      augmentation was observed when more than 1.8 microg of Fungizone was injected
      intravenously before intravenous dosing of FK23. The time interval between
      priming injection of Fungizone and secondary injection of FK23 for the maximal
      effect was 3 h. Similar augmentation of TNF production was also observed in
      amphotericin B-primed and FK23-injected mice. Correspondingly, anti-tumour
      activity of the combined, intravenous injection of Fungizone and FK23 with a 3-h
      interval was examined. Growth of Meth A fibrosarcoma was clearly inhibited by
      this combination but not by administration of either one alone. These results
      suggest that amphotericin B is able to elicit anti-tumour activity, perhaps
      through activation of the immune system, and in particular augmentation of the
      induction of endogenous TNF.

PMID- 9184175
TI  - Growth of methionine-dependent human prostate cancer (PC-3) is inhibited by
      ethionine combined with methionine starvation.
AB  - Methionine (MET) is required for cell metabolism. MET endogenously synthesized
      from homocysteine (HCY) supports the proliferation of normal cells, but not that
      of numerous malignant cells, as shown previously. MET starvation should have an
      anti-tumour effect, and its deleterious effects on the hosts might be prevented
      by HCY. Anti-tumour effects of MET starvation must be reinforced by ethionine
      (ETH), a MET analogue. MET dependency of PC-3, a human prostate cancer cell line,
      was studied in vitro. Proliferation of PC-3 cells, cultivated in MET-free medium,
      was 29% compared with growth in MET+HCY- medium. Addition of HCY to MET-free
      medium increased the proliferation rate to 56%. The concentration of ETH required
      to decrease the PC-3 cell proliferation rate to 50% (IC50) was 0.5 mg ml(-1) in
      MET-HCY- medium. ETH-induced inhibition was abolished by MET addition and was
      reinforced by HCY. PC-3 cell cycle was blocked in the S-G2-phase after 30 h
      culture in the absence of MET; this blockage was not reversed by addition of HCY.
      ETH at the IC50 in MET-HCY+ medium blocked DNA replication. Apoptotic cells
      appeared after 30 h incubation in MET-HCY+ medium only when ETH was added. ATP
      pools were decreased after 15 h of culture in MET-free medium. In vivo, MET
      starvation was obtained by feeding tumour-bearing mice a diet containing a
      synthetic amino acid mixture as the protein supply, in which HCY replaced MET.
      Given to nude mice bearing xenografted PC-3, from day 1 after grafting and for 3
      weeks, this diet inhibited tumour growth (34% on day 20, P < 0.007); this effect
      was potentiated by ETH (200 mg kg(-1) day(-1) i.p.) (56% on day 20, P < 5 x 10(
      5)). The differences between the effects of these two treatments were significant
      (P < 0.017) and optimal on day 20. These data showed that combination of ETH and
      HCY slowed the proliferation of prostate cancer cells in vitro and in vivo,
      decreased ATP synthesis and caused cell cycle arrest and apoptosis. Experimental
      therapy based on cancer cell MET metabolism deficiency could be efficient for
      treating advanced prostate cancers refractory to current therapies.

PMID- 9184177
TI  - Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric
      carcinoma.
AB  - Previous studies have shown that tumour-suppressor genes play an important role
      in the progression of solid tumours. Recently, the p21WAF1/CIP1 tumour-suppressor
      protein has been reported to work as a critical downstream effector of p53 and a
      potent inhibitor of cyclin-dependent kinases. Thus, the p21WAF1/CIP1 gene is
      thought to play a central role in tumour suppression. In this study we
      investigated p21 protein expression in gastric carcinomas. A total of 172 primary
      gastric carcinoma specimens were immunohistochemically stained for p21 protein
      expression. Correlations between p21 expression and clinicopathological features
      were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues
      (60.4%), and the frequency of p21 loss increased as the stage progressed.
      Expression of p21 in the primary tumour was frequently lost in patients with
      either lymph node, liver or peritoneal metastases as compared with patients
      without metastases. In patients with p21-negative tumours, the risk of recurrence
      following curative surgery was significantly higher, and the prognosis was
      significantly poorer than in patients with p21-positive tumours. Loss of p21
      expression in primary gastric carcinoma correlates with disease progression. The
      status of p21 gene expression may have prognostic value in this disease.

PMID- 9184178
TI  - The location of acidic fibroblast growth factor in the breast is dependent on the
      activity of proteases present in breast cancer tissue.
AB  - Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4,
      were localized in cryostat sections of normal, benign and malignant human breast
      tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly
      seen in normal epithelial cells. However, polymerase chain reaction (PCR)
      analysis and immunoblotting of isolated normal epithelial and myoepithelial cells
      showed FGF1 mRNA and protein to be present in both cell types. Following
      incubation of frozen sections at 37 degrees C in phosphate-buffered saline, FGF1
      staining was also revealed in myoepithelial cells and basement membrane adjacent
      to carcinoma cells. Treatment with protease inhibitors demonstrated that this
      effect was due to the activity of an endogenous protease. In contrast, FGF1
      staining was found to be associated with the stroma adjacent to malignant cells
      only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was
      localized to both normal and malignant epithelial cells and to a lesser extent to
      myoepithelial cells. There was no difference in the staining intensity for the
      FGF receptors between normal and cancer samples. The change in location of FGF1
      between normal and malignant tissues and the sensitivity of stored FGF1 to the
      action of endogenous proteases raises the possibility of both autocrine and
      paracrine roles for FGF1 in the normal and malignant human breast.

PMID- 9184179
TI  - Expression of insulin-like growth factors (IGFs), their receptors and IGF binding
      protein-3 in normal, benign and malignant smooth muscle tissues.
AB  - To assess the role of insulin-like growth factors (IGFs) in growth and
      transformation of normal (myometrium) and tumorous smooth muscle cell (SMC)
      tissues, in situ hybridization (ISH) analysis for insulin-like growth factor I
      and II (IGF-I and IGF-II) mRNAs was combined with detection of IGF peptides,
      their receptors and IGF binding protein-3 (IGFBP-3). mRNAs for both IGFs were
      detected in smooth muscle cells in normal, benign and malignant SMC tissues,
      together with the IGF peptides, both IGF receptors and IGFBP-3. This suggests an
      autocrine role for both IGFs. Leiomyomas had higher IGF-I peptide levels and
      higher levels of type I IGF receptors than myometrium, supporting the idea that
      IGFs play a role in the growth and transformation of these tumours. Low-grade
      leiomyosarcomas contained more IGF-II mRNAs than myometrium and leiomyoma, fewer
      type II IGF/mannose 6-phosphate receptors and less IGFBP-3 than myometrium and,
      in addition, fewer IGF-I mRNAs and type I IGF receptors than leiomyoma.
      Intermediate- and high-grade leiomyosarcomas had intermediate levels of IGF-II
      mRNAs and peptide, ranging between those in myometrium and low-grade
      leiomyosarcomas. Thus, growth and transformation of leiomyosarcomas may be
      regulated by IGF-II, although more markedly in low-grade than in high-grade
      leiomyosarcomas. In conclusion, the various categories of SMC tissues are
      associated with a distinct expression pattern of the IGF system. This suggests
      that each category of SMC tumours arises as a distinct entity and that there is
      no progression of transformation in these tissues.

PMID- 9184181
TI  - Immunohistochemical localization of prostate-specific antigen in benign and
      malignant breast tissues.
AB  - Prostate-specific antigen (PSA), a glycoprotein initially thought to be produced
      only by the epithelial cells of the prostate, has recently been found in 30% of
      female breast tumours using immunofluorometry. Our aim was to localize PSA
      immunohistochemically in a selected group of 27 paraffin-embedded breast tissues.
      A scoring system was developed for the histological assessment of PSA positivity
      within the breast tissue. One pathologist (DH) scored, classified and graded all
      tumours. Site-specific PSA staining was noted in the histology slides. Intense
      staining was identified in apocrine metaplasia and within the lining ductal
      epithelium of cystically dilated ducts. The epithelium in lesions of sclerosing
      adenosis was also frequently positive for PSA staining. Hyperplastic ductal
      epithelium (especially of mild degree) occasionally stained positive, as did
      normal breast ducts. Better differentiated tumours showed PSA staining [e.g.
      mucinous carcinoma (colloid)]. If an infiltrating duct carcinoma showed staining
      for PSA, adjacent intraductal carcinoma was also noted to stain positively, if
      present.

PMID- 9184180
TI  - BCL-6 and other genomic alterations in non-Hodgkin's lymphoma (NHL).
AB  - This study reports on the frequency and disease association pattern of a number
      of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected
      the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of
      mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearranged in
      42% of follicle centre lymphomas (FCL) and in 15% of diffuse large B-cell (DLBC)
      lymphomas. In this study, 80% of the c-MYC rearrangements were detected in
      aggressive diffuse lymphoma subsets but, interestingly, 9% of FCL showed
      involvement of t(8q24) translocation. In our study, rearrangements of the BCL-6
      gene at band 3q27 were found in 31% of DLBC lymphomas. Interestingly, 50% of the
      BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements
      involving all of the aforementioned gene loci. The molecular dissection of these
      genes will improve our understanding of the genesis of the diverse
      clinicopathological subtypes.

PMID- 9184182
TI  - Breast cancer management: is volume related to quality? Clinical Advisory Panel.
AB  - A method of carrying out region-wide audit for breast cancer was developed by
      collaboration between the cancer registry, providers and purchasers as part of
      work to fulfill the 'Calman-Hine' recommendations. In order to test the audit
      method, a retrospective audit in North Thames East compared practice in 1992
      against current guidelines. The analysis compared care in specialist and non
      specialist centres. A stratified random sample comprising 28% of all breast
      cancer patients diagnosed in 1992 was selected from the population-based Thames
      Cancer Registry. The data for 309 patients with stage I-III tumours were analysed
      by hospital type using local guidelines. No difference between specialist (high
      volume) and non-specialist centres was detected for factors important in
      survival. Pathological staging was good with over 70% reporting tumour size and
      grade. A small number of patients were undertreated; after conservative surgery,
      10% (19) of women did not receive radiotherapy, and 15% (8) of node-positive
      premenopausal women did not receive chemotherapy or ovarian ablation. In
      contrast, a significant trend with hospital volume was found for several quality
      of life factors. These included access to a specialist breast surgeon and
      specialist breast nurses, availability of fine-needle aspiration (FNA), which
      ranged from 84% in high-volume to 42% in low-volume centres, and quality of
      surgery (axillary clearance rates ranged from 51% to 8% and sampling of less than
      three nodes from 3% to 25% for high- and very low-volume centres respectively).
      Confidential feedback of results to surgeons was welcomed and initiated change.
      The summary information gave purchasers information relevant to the evaluation of
      cancer services. While the audit applied present standards to past practice, it
      provided the impetus for prospective audit of current practice (now being
      implemented in North Thames).

PMID- 9184183
TI  - Randomized comparison of etoposide pharmacokinetics after oral etoposide
      phosphate and oral etoposide.
AB  - Etoposide phosphate is a water-soluble prodrug of etoposide. The plasma
      pharmacokinetics of etoposide following oral administration of etoposide
      phosphate or oral etoposide were compared. Seventeen patients with solid tumours
      were enrolled to receive oral etoposide phosphate 125 mg m(-2) on days 1-5 every
      3 weeks, with escalation to 175 mg m(-2) from course 3 when possible. Patients
      were randomized to receive oral etoposide phosphate or oral etoposide on day 1 of
      course 1 and the alternative compound on day 1 of course 2. Fifteen patients
      received two or more courses and were evaluable for pharmacokinetic comparisons.
      The median AUC(inf) (area under the concentration vs time curve from zero to
      infinity) of etoposide was 77.7 mg l(-1) h after etoposide phosphate (95% CI 61.3
      100.5) and 62.0 mg l(-1) h after oral etoposide (95% CI 52.2-76.9). The
      difference in favour of etoposide phosphate was borderline significant: median
      9.9 mg l(-1) h (95% CI 0.1-32.8 mg l(-1) h; P = 0.05). However, the inter-patient
      variability of etoposide AUC(inf) was not improved (coefficients of variation
      42.3% and 48.4%). Etoposide phosphate was undetectable in plasma after oral
      administration. Toxicities of oral etoposide phosphate were not different from
      those known for etoposide. In conclusion, oral etoposide phosphate does not offer
      a clinically relevant benefit over oral etoposide.

PMID- 9184184
TI  - c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in
      breast carcinomas correlates with patients' overall and disease-free survival.
AB  - The prognostic significance of c-erbB-2 oncoprotein overexpression detected in
      tumours by immunocytochemical assays (ICAs) was investigated in 148 breast
      carcinomas. ICAs were performed under optimal technical conditions with frozen
      tissue sections and included automated immunoperoxidase technique and computer
      assisted analysis (densitometry) of digitized coloured microscopic images.
      Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive
      surfaces and mean optical densities) were correlated with the patients' follow-up
      in axillary lymph node-positive (N+) and node-negative (N-) subgroups of
      patients. Patients' follow-up ranged from 9 months (for the first death) to 101
      months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It
      was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off
      point 35%) significantly correlated with the patients' poor overall survival in
      N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015).
      Also, marked c-erbB-2 immunohistochemical expression correlates with short
      disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free
      survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups.
      It is concluded that in optimal conditions (automated and quantitative ICAs on
      frozen sections) c-erbB immunohistochemical expression is a significant
      prognostic indicator in terms of overall and disease-free survival. The c-erbB-2
      protein prognostic significance is independent of node status in terms of overall
      survival, but not of disease-free survival.

PMID- 9184185
TI  - Soluble ectodomain of c-erbB-2 oncoprotein in relation to tumour stage and grade
      in human renal cell carcinoma.
AB  - The soluble ectodomain of c-erbB-2 oncoprotein was measured using a sandwich
      enzyme immunoassay in sera from 184 patients with renal cell carcinoma before
      initiation of treatment. The median serum level was 2062 U ml(-1) (range 865-4905
      U ml(-1)). Levels were unaffected by sex, age and renal function. An inverse
      relation between disease stage (P = 0.0017) and tumour grade (P = 0.0009) and the
      serum level of c-erbB-2 ectodomain was observed. Survival time for patients with
      serum levels above median level was significantly longer than for patients with
      lower levels (P = 0.003). In a multivariate analysis, c-erbB-2 oncoprotein lost
      its prognostic information, while tumour stage and tumour grade were identified
      as independent prognostic factors.

PMID- 9184186
TI  - TIMP-3 mRNA expression is regionally increased in moderately and poorly
      differentiated colorectal adenocarcinoma.
AB  - In this study, we report on the distribution of tissue inhibitor of matrix
      metalloproteinase-3 (TIMP-3) mRNA expression in human normal colorectal mucosa,
      adenomas and adenocarcinomas. Northern blot analysis showed five TIMP-3 mRNA
      transcripts to be present in normal mucosal epithelium and in moderately and
      poorly differentiated carcinoma. Adenomas and well-differentiated carcinomas were
      not examined in this part of the investigation. In situ hybridization studies
      showed no detectable TIMP-3 mRNA in normal and adenomatous tissue. In contrast,
      TIMP-3 mRNA is localized to stromal fibroblast-like cells in colorectal
      carcinomas, with an increased incidence in moderately and poorly differentiated
      groups compared with well-differentiated carcinomas. Expression in both the
      moderately and the poorly differentiated tumour groups was strongest at the
      tumour invasive edge; none of the poorly differentiated carcinomas showed mRNA
      expression in regions ahead of the invasive edge, compared with 3 of 12 of the
      moderate group. To our knowledge, this is the first detailed report on the
      regional localization of TIMP-3 mRNA in colorectal tumours. We suggest that the
      lack of TIMP-3 mRNA expression in host stromal tissues ahead of poorly
      differentiated carcinomas may contribute to their increased invasiveness.

PMID- 9184187
TI  - Comparison of marrow vs blood-derived stem cells for autografting in previously
      untreated multiple myeloma.
AB  - Sixty-three new untreated patients with multiple myeloma under the age of 70
      years received C-VAMP induction treatment followed by high-dose intravenous
      melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow
      [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony
      stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood
      stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two
      groups were not significantly different for all known prognostic variables. The
      complete remission (CR) rate after high-dose treatment was the same for both
      groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to
      0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared
      with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(
      1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015),
      and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P =
      0.00001). There was no difference in the two groups with respect to starting
      interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon
      was identical. The median overall survival (OS) and progression-free survival
      (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT
      patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%)
      in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was
      53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P =
      NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared
      with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster
      engraftment and a shorter stay in hospital than ABMT; the survival outcome and
      probability of relapse was the same for both groups.

PMID- 9184188
TI  - The dose-response relationship between cigarette consumption, biochemical markers
      and risk of lung cancer.
AB  - The relationship between the number of cigarettes smoked per day and the
      incidence of lung cancer is linear but, from the multistage model of
      carcinogenesis, it should be quadratic (upwards curving). We investigated this
      anomaly in a study of 11,403 male never smokers and current smokers in whom
      carboxyhaemoglobin (COHb) was measured in all and serum cotinine in 1175. The
      relationship between the biochemical markers and the reported number of
      cigarettes per day was approximately linear up to 20 cigarettes per day as
      expected. But above 20 cigarettes per day the marker levels increased less
      steeply and were 35% lower than expected in men who smoked more than 40
      cigarettes per day. Less smoke is inhaled from each cigarette by men with high
      daily cigarette consumption than by men with lower consumption. Allowance for
      this transforms the observed linear dose-response relationship into one
      consistent with the expected quadratic relationship. The anomaly is explained by
      the observation that heavier smokers inhale less smoke from each cigarette.

PMID- 9184189
TI  - Comparison of the diagnosis of leukaemia from death certificates, cancer
      registration and histological reports - implications for occupational case
      control studies.
AB  - It is essential in occupational case-control studies of rare diseases for
      ascertainment to be as complete as possible, together with an accurately defined
      diagnosis. A nested case-control study from a large cohort of UK oil distribution
      workers followed up since 1950 was carried out to investigate the association
      between leukaemia, in particular acute myeloid leukaemia, and exposure to
      benzene. Ninety-one cases occurring before 1993 were identified from death
      certificates or cancer registrations (available from 1971). Histopathology
      departments were contacted to obtain material that might confirm the diagnosis of
      leukaemia and this was received for 39 (43%) cases. The majority of the cases
      (88) were identified primarily from death certificates, with a cancer
      registration also being received for 56 (90%) of the 62 deaths occurring after
      1971. Discrepancies in the diagnoses from these two sources were found for 12
      cases, five being acute myeloid leukaemia. For the majority, the diagnosis on the
      death certificate was more specific than that on the cancer registration.
      Histology reports were received for nine of the discrepancies, all confirming the
      death certificate diagnosis. Although leukaemia appears to be regularly
      registered as a cancer, records may not be routinely updated when new clinical
      information becomes available. It is recommended that death certificates, cancer
      registrations and histology reports are obtained routinely by cancer registries
      to maximize both numbers of cases and diagnostic accuracy for epidemiological
      studies.

PMID- 9184190
TI  - Selected medical conditions and risk of breast cancer.
AB  - Several diseases are known or suspected to be associated with altered levels of
      hormones and growth factors that may influence breast cancer risk. To elucidate
      this possibility, we studied the relationship between 23 medical conditions or
      procedures and breast cancer risk by means of data from a multicentric case
      control study conducted between 1991 and 1994 in six Italian areas. The study
      included 2569 histologically confirmed incident cases of breast cancer (median
      age 55 years, range 23-74 years) and 2588 control women (median age 56 years,
      range 20-74 years) admitted to the same hospitals as cases for a variety of acute
      conditions unrelated to known or suspected risk factors for breast cancer. After
      allowance for education, parity and body mass index, elevated odds ratios (ORs)
      emerged for history of diabetes mellitus in post-menopausal women (OR = 1.5, 95%
      CI 1.1-2.0), hypertension in pregnancy (OR = 1.8, 95% CI 1.0-3.4) and breast
      nodules (OR = 1.3, 95% CI 1.0-1.7). Risk decreases were associated with ovarian
      ablation for ovarian cysts (OR = 0.5, 95% CI 0.3-0.7) and with thyroid nodules
      (OR = 0.7, 95% CI 0.5-0.9) but not with the combination of any type of benign
      thyroid disease. While most examined conditions seemed unrelated to breast cancer
      risk, the association with late-onset diabetes is of special interest as it
      suggests a role of hyperinsulinaemia and insulin resistance in breast cancer
      promotion. It also points to preventive lifestyle modifications.

PMID- 9184191
TI  - Association between human immunodeficiency virus type 1 infection and cancer in
      the black population of Johannesburg and Soweto, South Africa.
AB  - A case-control study of 913 black cancer patients (aged 15-50 years) was
      undertaken to measure the association between human immunodeficiency (HIV)
      infection and cancers believed to have an infective aetiology. Controls were
      patients with cancers believed not to be infective in origin. The prevalence of
      HIV in the controls of 7.3% (24 of 325) was similar to the background HIV
      seropositivity in this population. Odds ratios (ORs) and 95% confidence intervals
      (CI) adjusted for age, year of diagnosis, marital status and sex were calculated.
      There was a strong association between HIV infection and Kaposi's sarcoma (KS),
      with 27 of 33 cases being HIV seropositive, OR = 61.8 (95% CI 19.7-194.2) and an
      elevated association with non-Hodgkin's lymphoma (NHL), with 27 of 40 cases being
      HIV seropositive [OR = 4.8 (95% CI 1.5-14.8)]. The elevated odds ratio for KS
      associated with HIV infection accords with the observed increases in the
      incidence of KS in several sub-Saharan African countries where the prevalence of
      HIV is high. The odds ratio for NHL associated with HIV infection was lower than
      that reported in developed countries, and the reason for this is not clear. No
      other cancers, including cervical and liver cancers, showed significantly
      elevated odds ratios associated with HIV infection.

PMID- 9184192
TI  - Clinicopathological features of bladder cancer associated with chronic exposure
      to arsenic.
AB  - A high incidence of bladder cancer has been documented in an area of chronic
      arsenic (As) exposure. This study investigates the characteristics of As
      associated (n = 49) and other (n = 64) bladder cancers. A higher histological
      grading was observed for the As-exposed tumours (P = 0.04), but no other
      difference in pathobiological features or prognosis was found between the two
      groups.

PMID- 9184194
TI  - Antimitotic intervention with colchicine alters the outcome of o-DCB-induced
      hepatotoxicity in Fischer 344 rats.
AB  - Although, hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) is greater in Fischer
      344 (F344) as compared to Sprague-Dawley (S-D) rats, this interstrain difference
      does not transcend into any difference in lethal effects of o-DCB. Interstrain
      difference in compensatory tissue repair has been suggested as the underlying
      mechanism for the lack of strain differences in lethality (S.G. Kulkarni, H.
      Duong, R. Gomila, and H.M. Mehendale, Strain differences in tissue repair
      response to 1,2-dichlorobenzene. Archives of Toxicology 1996; 70: 714-723). If
      higher tissue repair in F344 rats compensates for more severe liver injury, then
      antimitotic intervention after infliction of o-DCB-induced liver injury should
      lead to lethality in F344 rats. Colchicine (CLC, 1 mg/kg) functions as an
      effective antimitotic agent and does not cause any side effects apart from
      suppressing cellular proliferation. Two groups of male F344 rats (160-190 g)
      received a single dose of 0.6 ml o-DCB/kg: 30 h later one group of rats received
      CLC (1 mg/kg; i.p.) and the other received distilled water (1 ml/kg; i.p.). Liver
      injury was assessed by measuring plasma ALT and SDH activity, liver
      histopathology, and liver regeneration was estimated by [3H]thymidine
      incorporation into hepatonuclear DNA and proliferating cell nuclear antigen
      (PCNA) assay in both groups. Similar liver injury was noted in both the o-DCB +
      vehicle and o-DCB + CLC treated F344 rats at 36 h indicating that CLC does not
      interfere with the uptake, bioactivation and causation of injury by o-DCB. S
      phase synthesis which occurred at 36 h in the o-DCB + vehicle group was blocked
      in the o-DCB + CLC group. CLC administration 6 h prior to S-phase stimulation
      selectively abolished S-phase stimulation at 36 h, and led to 50% lethality.
      Since the effect of CLC antimitosis was transient, S-phase synthesis occurring at
      48 h was not blocked and was sustained up to 72 h thereby allowing the other 50%
      of rats to overcome liver injury induced by o-DCB and survive the lethal outcome.
      These findings suggest that a significantly higher rate of compensatory tissue
      repair in F344 rats enables them to overcome more severe liver injury inflicted
      by o-DCB.

PMID- 9184193
TI  - Seasonality in the diagnosis of acute lymphocytic leukaemia.
AB  - Literature on seasonality of leukaemia shows conflicting results. We analysed the
      month of diagnosis of acute leukaemia in East Anglia, UK, for the period 1971-94,
      which showed a significant 40% summer excess (P < 0.001) for acute lymphocytic
      leukaemia both in children (P < 0.01) and adults (P = 0.01). Methodology, results
      and possible aetiological interpretations are presented.

PMID- 9184195
TI  - Aluminum citrate is transported from brain into blood via the monocarboxylic acid
      transporter located at the blood-brain barrier.
AB  - Aluminum citrate transport across the blood-brain barrier was assessed in rats by
      in vivo microdialysis. Microdialysis probes were implanted in the jugular vein as
      well as the left and right frontal cortex. It was demonstrated previously (Allen
      et al., 1995), in this study, that the steady-state aluminum citrate brain-to
      blood-ratio (BBr) is less than 1, suggesting the presence of a process other than
      diffusion. The addition of 2,4-dinitrophenol (10 microM) to the dialysate
      perfusing a microdialysis probe in the brain increased the steady-state aluminum
      citrate brain-to-blood-ratio to a value (1.14) not significantly different from
      1, suggesting the presence of an active transporter that is blocked by the
      metabolic inhibitor. The addition of valproic and pyruvic acid, as putative and
      known substrates for the monocarboxylic acid transporter, respectively, to brain
      dialysate (10 and 100 mM) had different outcomes. Valproic acid was ineffective
      at either concentration, whereas pyruvic acid (100 mM) significantly increased
      the aluminum citrate brain-to-blood-ratio from 0.19 to 0.31. Pyruvic acid (1 M in
      the dialysate) increased the aluminum citrate brain-to-blood-ratio to a value not
      different from unity, suggesting competition between aluminum citrate and pyruvic
      acid for transport. The only energy-dependent, pyruvic acid-inhibitable
      transporter is the monocarboxylic acid transporter. Theoretical, pharmacokinetic
      modeling suggests that the transporter producing an aluminum citrate brain-to
      blood-ratio less than 1 is predominantly located at the blood-brain barrier,
      rather than at neuronal or glial cell membranes. We propose that the
      monocarboxylic acid transporter at the blood-brain barrier maintains a steady
      state aluminum citrate brain-to-blood-ratio much less than 1.

PMID- 9184196
TI  - Effects of low concentrations of 3-carene on alveolar macrophages in vitro.
AB  - Rat alveolar macrophages (AM) were incubated with the monoterpene 3-carene in
      vitro at the concentrations 0, 0.005, 0.05, 0.5 and 5.0 microM in culture medium
      for 75 min. A dose-dependent relationship was found between the cell viability
      and the 3-carene concentration. At 5.0 microM 3-carene, 98% of the AM were dead.
      The phagocytosis of heat-killed yeast particles was significantly decreased and
      the attachment of particles to the cell surface significantly increased at 0.5
      microM 3-carene. Electron microscopy showed that about 50% of the AM lacked or
      had very few surface protrusions after incubation in 0.5 microM 3-carene. Thus, 3
      carene seemed to affect mainly the engulfment of particles. Surfactant, 0.5 mg/ml
      as Curosurf, added to the incubation medium, did not affect the AM reaction to 3
      carene exposure.

PMID- 9184197
TI  - A model for quantitative measurement of sulfur mustard skin lesions in the rabbit
      ear.
AB  - The search for treatment and protection against the vesicant and inflammatory
      skin lesions induced by sulfur mustard suffers from the lack of a good in vivo
      reproducible model. We applied sulfur mustard (25-500 microg/cm2) to the outer
      surface of the ears of 10 rabbits and measured the edema formation 12, 24 and 48
      h post-application with a caliper especially designed for soft matter. There was
      a dose-dependent linear increase in edema magnitude in the range from 25 to 150
      microg/cm2. Maximal edema was observed after 12 h. There was a 12% reduction in
      edema size 24 h after application and a further decrease after 48 h. Skin
      thickness, inflammatory cell infiltrate, necrosis and vesiculation were evaluated
      in biopsies taken after 24 h. We found the same dose-related increase both in
      skin thickness and in degree of blister formation. This simple dose-response in
      vivo model can be used for evaluation of the dermal inflammation induced by
      topical application of sulfur mustard. This model has the additional advantage of
      a built-in control, namely the untreated contralateral ear. Consequently, this
      model can serve as a useful tool for future screening of potential compounds for
      prevention and treatment of sulfur mustard-induced skin lesions.

PMID- 9184198
TI  - Changes in high molecular weight DNA fragmentation following human blood exposure
      to styrene-7,8-oxide.
AB  - Styrene-7,8-oxide (S7,8O) is the major in vivo metabolite of styrene and is a
      genotoxic agent potentially carcinogenic to humans. It is known to cause DNA
      strand breaks and adducts. We studied high molecular weight DNA fragmentation in
      white blood cells following incubation of blood with S7,8O from individuals with
      no previous exposure to this compound. To better understand the effects of S7,8O,
      we also examined blood exposed to hydrogen peroxide (H2O2) a typical oxidant that
      is linked to oxidative stress. All individuals in this study showed a variable
      reduction in high molecular weight DNA fragments determined by laser densitometry
      compared to untreated controls for both S7,8O and H2O2 treated samples. This
      decrease was independent of the concentration and length of exposure of blood to
      S7,8O and H2O2. An increase in low molecular weight DNA fragments from samples
      treated with S7,8O and H2O2, compared to untreated samples was also noted.
      Similarities in the reduction of HMW-DNA fragments after S7,8O and H2O2 exposure
      suggested a similar mechanism of HMW-DNA damage. It was surmised that S7,8O
      exposure in blood may induce high molecular weight DNA fragmentation due to
      oxidative stress.

PMID- 9184199
TI  - Kupffer cells from halothane-exposed guinea pigs carry trifluoroacetylated
      protein adducts.
AB  - The anesthetic, halothane, is bioactivated by the liver cytochrome P450 system to
      trifluoroacetyl-chloride, which can readily acylate liver protein. Covalent
      binding of the trifluoroacetyl moiety may result in hapten formation leading to
      the induction of an immune response and ultimately halothane hepatitis. In this
      study the presence of trifluoroacetylated-protein adducts in Kupffer cells was
      investigated to learn how the immune system might come in contact with the
      proteins. Guinea pigs were exposed to 1.0% halothane, 40% oxygen for 4 h. Kupffer
      cells were isolated on days 1 through 9 post-exposure, by liver perfusion and
      purification by elutriation. Using gel electrophoresis and Western blotting
      techniques, it has been demonstrated that Kupffer cells obtained from halothane
      treated guinea pigs, do carry trifluoroacetyl-protein adducts as recognized by an
      anti-trifluoroacetyl-rabbit serum albumin antibody. Apparent molecular weights of
      polypeptides bound by trifluoroacetyl were of a wide range, 25-152 kDa. Bands
      were most prominent in the larger Kupffer cells with more appearing at lower
      molecular weights. Trifluoroacetyl-protein adducts were not detected in lung,
      spleen, lymph node or peripheral blood macrophages. This work suggests a role for
      Kupffer cells in the presentation of altered proteins in the liver to cells of
      the immune system.

PMID- 9184200
TI  - Comparative study of the damage produced by acute ethanol and acetaldehyde
      treatment in a human fetal hepatic cell line.
AB  - The effects of acute ethanol and acetaldehyde treatment on cell proliferation,
      cell adhesion capacity, neutral red incorporation into lysosomes, glutathione
      content, protein sulfhydryl compounds, lipid peroxidation, inner mitochondrial
      membrane integrity (MTT test), lactate dehydrogenase activity (LDH) and
      ultrastructural alterations were investigated in a human fetal hepatic cell line
      (WRL-68 cells). WRL-68 cells were used, due to the fact that, although this cell
      line expresses some hepatic characteristics, it does not express alcohol
      dehydrogenase or cytochrome P450 activity, so it could be a good model to study
      the effect of the toxic agents per se. Cells were exposed during 120 min with 200
      mM ethanol or 10 mM acetaldehyde. Under these conditions, cells presented 100%
      viability and no morphological alteration was observed by light microscopy.
      Acetaldehyde-treated cells reduced their proliferative capacity drastically while
      the ethanol-treated ones presented no difference with control cells. Cell
      adhesion to substrate, measured as time required to adhere to the substrate and
      time required to detach from the substrate, was diminished in acetaldehyde WRL-68
      treated cells. Cytotoxicity measures as neutral red and MTT test showed that
      acetaldehyde-treated cells presented more damage than ethanol-treated ones.
      Cellular respiratory capacity was compromised by acetaldehyde treatment due to
      40% less oxygen consumption than control cells. Lipid peroxidation values,
      measured as malondialdehyde production, were higher in ethanol-treated WRL-68
      cells (127%) than in acetaldehyde-treated ones (60%) to control cell values.
      Lactate dehydrogenase activity (LDH) in extracellular media of ethanol-treated
      cells presented the highest values. GSH content was reduced 95% and thiol protein
      content was diminished severely in acetaldehyde-treated cells. Transmission
      electron microscopy showed more ultrastructural alterations in cells treated with
      acetaldehyde. The results indicate that acetaldehyde, like ethanol, produced
      damage at cellular level, although more damage could be observed in acetaldehyde
      WRL-68-treated cells.

PMID- 9184201
TI  - Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a
      four-week study in cynomolgus monkeys.
AB  - The toxicity of ISIS 2302, a phosphorothioate oligonucleotide with antisense
      activity against human ICAM-1 mRNA, was investigated in cynomolgus monkeys (young
      adult). The oligonucleotide was administered by slow bolus injection every other
      day for 28 days (14 doses) at dose levels of 0, 2, 10, and 50 mg/kg/injection.
      The basic group size consisted of three male and three female monkeys which were
      sacrificed 2 days after the last dose. An additional 2 monkeys/sex in the vehicle
      control and 50 mg/kg dose groups remained on study for a 28-day treatment-free
      period. No treatment-related deaths occurred during this study, however, one
      monkey in the 10 mg/kg dose group was markedly lethargic after the first dose.
      Other clinical observations included periocular swelling (> or = 10 mg/kg) on the
      first day of the study, and bruising in all dose groups throughout the study.
      Bruising was associated with a dose-dependent prolongation of clotting times,
      particularly activated partial thromboplastin times (APTT), that was transient in
      nature. Bruises occurred around site of intravenous dosing or blood collection,
      and were manifested as subcutaneous hemorrhages upon microscopic evaluation.
      There were no corresponding alterations in hematology parameters including RBC or
      platelet counts. Other treatment-related microscopic alterations noted were
      intracytoplasmic eosinophilic granules and vacuolation in proximal tubular
      epithelial cells at 10 and 50 mg/kg, with free RBC in renal proximal tubular
      lumens at 50 mg/kg. Serum chemistry parameters including BUN and creatinine
      levels were normal in all dose groups and there were no notable alterations in
      urinalysis parameters. Granules and vacuolations in kidneys were reversed
      following a 4-week treatment free period. In general, 10 and 50 mg/kg ISIS 2302
      produced dose-dependent changes in clotting times and the kidney that were
      reversible, while 2 mg/kg ISIS 2302 produced no remarkable alterations.

PMID- 9184202
TI  - The bacteriophage phi29 head-tail connector imaged at high resolution with the
      atomic force microscope in buffer solution.
AB  - The surfaces of two- and three-dimensional phi29 connector crystals were imaged
      in buffer solution by atomic force microscopy (AFM). Both topographies show a
      rectangular unit cell with dimensions of 16.5 nm x 16.5 nm. High resolution
      images of connectors from the two-dimensional crystal surface show two connectors
      per unit cell confirming the p42(1)2 symmetry. The height of the connector was
      estimated to be at least 7.6 nm, a value close to that found in previous studies
      using different techniques. The 12 subunits of the wide connector domain were
      clearly resolved and showed a right-handed vorticity. The channel running along
      the connector had a diameter of 3.7 nm in the wide domain, while it was 1.7 nm in
      the narrow domain end, thus suggesting a tronco-conical channel shape. Moreover,
      the narrow connector end appears to be rather flexible. When the force applied to
      the stylus was between 50 and 100 pN, the connector end was fully extended. At
      forces of approximately 150 pN, these ends were pushed towards the crystal
      surface. The complementation of the AFM data with the three-dimensional
      reconstruction obtained from electron microscopy not only confirmed the model
      proposed, but also offers new insights that may help to explain the role of the
      connector in DNA packing.

PMID- 9184203
TI  - Phytochrome-regulated repression of gene expression requires calcium and cGMP.
AB  - The plant photoreceptor phytochrome A utilizes three signal transduction
      pathways, dependent upon calcium and/or cGMP, to activate genes in the light. In
      this report, we have studied the phytochrome A regulation of a gene that is down
      regulated by light, asparagine synthetase (AS1). We show that AS1 is expressed in
      the dark and repressed in the light. Repression of AS1 in the light is likely
      controlled by the same calcium/cGMP-dependent pathway that is used to activate
      other light responses. The use of the same signal transduction pathway for both
      activating and repressing different responses provides an interesting mechanism
      for phytochrome action. Using complementary loss- and gain-of-function
      experiments we have identified a 17 bp cis-element within the AS1 promoter that
      is both necessary and sufficient for this regulation. This sequence is likely to
      be the target for a highly conserved phytochrome-generated repressor whose
      activity is regulated by both calcium and cGMP.

PMID- 9184205
TI  - Calcineurin is required for virulence of Cryptococcus neoformans.
AB  - Cyclosporin A (CsA) and FK506 are antimicrobial, immunosuppressive natural
      products that inhibit signal transduction. In T cells and Saccharomyces
      cerevisiae, CsA and FK506 bind to the immunophilins cyclophilin A and FKBP12 and
      the resulting complexes inhibit the Ca2+-regulated protein phosphatase
      calcineurin. We find that growth of the opportunistic fungal pathogen
      Cryptococcus neoformans is sensitive to CsA and FK506 at 37 degrees C but not at
      24 degrees C, suggesting that CsA and FK506 inhibit a protein required for C.
      neoformans growth at elevated temperature. Genetic evidence supports a model in
      which immunophilin-drug complexes inhibit calcineurin to prevent growth at 37
      degrees C. The gene encoding the C. neoformans calcineurin A catalytic subunit
      was cloned and disrupted by homologous recombination. Calcineurin mutant strains
      are viable but do not survive in vitro conditions that mimic the host environment
      (elevated temperature, 5% CO2 or alkaline pH) and are no longer pathogenic in an
      animal model of cryptococcal meningitis. Introduction of the wild-type
      calcineurin A gene complemented these growth defects and restored virulence. Our
      findings demonstrate that calcineurin is required for C. neoformans virulence and
      may define signal transduction elements required for fungal pathogenesis that
      could be targets for therapeutic intervention.

PMID- 9184204
TI  - New structure and function in plant K+ channels: KCO1, an outward rectifier with
      a steep Ca2+ dependency.
AB  - Potassium (K+) channels mediating important physiological functions are
      characterized by a common pore-forming (P) domain. We report the cloning and
      functional analysis of the first higher plant outward rectifying K+ channel
      (KCO1) from Arabidopsis thaliana. KCO1 belongs to a new class of 'two-pore' K+
      channels recently described in human and yeast. KCO1 has four putative
      transmembrane segments and tandem calcium-binding EF-hand motifs. Heterologous
      expression of KCO1 in baculovirus-infected insect (Spodoptera frugiperda) cells
      resulted in outwardly rectifying, K+-selective currents elicited by depolarizing
      voltage pulses in whole-cell measurements. Activation of KCO1 was strongly
      dependent on the presence of nanomolar concentrations of cytosolic free Ca2+
      [Ca2+]cyt. No K+ currents were detected when [Ca2+]cyt was adjusted to <150 nM.
      However, KCO1 strongly activated at increasing [Ca2+]cyt, with a saturating
      activity observed at approximately 300 nM [Ca2+]cyt. KCO1 single channel analysis
      on excised membrane patches, resulting in a single channel conductance of 64 pS,
      confirmed outward rectification as well as Ca2+-dependent activation. These data
      suggest a direct link between calcium-mediated signaling processes and K+ ion
      transport in higher plants. The identification of KCO1 as the first plant K+
      outward channel opens a new field of structure-function studies in plant ion
      channels.

PMID- 9184206
TI  - Disruption of the trypanothione reductase gene of Leishmania decreases its
      ability to survive oxidative stress in macrophages.
AB  - Parasitic protozoa belonging to the order Kinetoplastida contain trypanothione as
      their major thiol. Trypanothione reductase (TR), the enzyme responsible for
      maintaining trypanothione in its reduced form, is thought to be central to the
      redox defence systems of trypanosomatids. To investigate further the
      physiological role of TR in Leishmania, we attempted to create TR-knockout
      mutants by gene disruption in L. donovani and L. major strains using the
      selectable markers neomycin and hygromycin phosphotransferases. TR is likely to
      be an important gene for parasite survival since all our attempts to obtain a TR
      null mutant in L. donovani failed. Instead, we obtained mutants with a partial
      trisomy for the TR locus where, despite the successful disruption of two TR
      alleles by gene targeting, a third TR copy was generated as a result of genomic
      rearrangements involving the translocation of a TR-containing region to a larger
      chromosome. Mutants of L. donovani and L. major possessing only one wild-type TR
      allele express less TR mRNA and have lower TR activity compared with wild-type
      cells carrying two copies of the TR gene. Significantly, these mutants show
      attenuated infectivity with a markedly decreased capacity to survive
      intracellularly within macrophages, provided that the latter are producing
      reactive oxygen intermediates.

PMID- 9184207
TI  - HIV-1-induced cell fusion is mediated by multiple regions within both the viral
      envelope and the CCR-5 co-receptor.
AB  - Although the human hCCR-5 chemokine receptor can serve as a co-receptor for both
      M-tropic (ADA and BaL) and dual-tropic (89.6) strains of human immunodeficiency
      virus type 1 (HIV-1), the closely related mouse mCCR-5 homolog is inactive. We
      used chimeric hCCR-5-mCCR-5 receptor molecules to examine the functional
      importance of the three extracellular domains of hCCR-5 that differ in sequence
      from their mCCR-5 equivalents. While this analysis revealed that all three of
      these extracellular domains could participate in the functional interaction with
      HIV-1 envelope, clear differences were observed when different HIV-1 strains were
      analyzed. Thus, while the ADA HIV-1 isolate could effectively utilize chimeric
      human-mouse CCR-5 chimeras containing any single human extracellular domain, the
      BaL isolate required any two human extracellular sequences while the 89.6 isolate
      would only interact effectively with chimeras containing all three human
      extracellular sequences. Further analysis using hybrid HIV-1 envelope proteins
      showed that the difference in co-receptor specificity displayed by the ADA and
      BaL isolates was due partly to a single amino acid change in the V3 loop,
      although this interaction was clearly also modulated by other envelope domains.
      Overall, these data indicate that the interaction between HIV-1 envelope and CCR
      5 is not only complex but also subject to marked, HIV-1 isolate-dependent
      variation.

PMID- 9184208
TI  - Recycling of the urokinase receptor upon internalization of the uPA:serpin
      complexes.
AB  - The GPI-anchored urokinase plasminogen activator receptor (uPAR) does not
      internalize free urokinase (uPA) but readily internalizes and degrades uPA:serpin
      complexes in a process that requires the alpha2-macroglobulin receptor/low
      density lipoprotein receptor-related protein (alpha2MR-LRP). This process is
      accompanied by the internalization of uPAR which renders it resistant to
      phosphatidylinositol-specific phospholipase C (PI-PLC). In this paper we show
      that during internalization of uPA:serpins at 37 degrees C, analysed by FACScan,
      immunofluorescence and immunoelectron microscopy, an initial decrease of cell
      surface uPAR was observed, followed by its reappearance at later times. This
      effect was not due to redistribution of previously intracellular receptors, nor
      to the surface expression of newly synthesized uPAR. Recycling was directly
      demonstrated in cell surface-biotinylated, uPA:PAI-1-exposed cells in which
      biotinylated uPAR was first internalized and subsequently recycled back to the
      surface upon incubation at 37 degrees C. In fact, uPAR was resistant to PI-PLC
      after the 4 degrees C binding of uPA:PAI-1 to biotinylated cells, but upon
      incubation at 37 degrees C PI-PLC-sensitive biotinylated uPAR reappeared at the
      cell surface. Binding of uPA:PAI-1 by uPAR, while essential to initiate the whole
      process, was, however, dispensable at later stages as both internalization and
      recycling of uPAR could be observed also after dissociation of the bound ligand
      from the cell surface.

PMID- 9184209
TI  - Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic
      mice reveals essential roles for TGF-beta in regulation of growth and
      differentiation in the exocrine pancreas.
AB  - Using a dominant-negative mutant receptor (DNR) approach in transgenic mice, we
      have functionally inactivated transforming growth factor-beta (TGF-beta)
      signaling in select epithelial cells. The dominant-negative mutant type II TGF
      beta receptor blocked signaling by all three TGF-beta isoforms in primary
      hepatocyte and pancreatic acinar cell cultures generated from transgenic mice, as
      demonstrated by the loss of growth inhibitory and gene induction responses.
      However, it had no effect on signaling by activin, the closest TGF-beta family
      member. DNR transgenic mice showed increased proliferation of pancreatic acinar
      cells and severely perturbed acinar differentiation. These results indicate that
      TGF-beta negatively controls growth of acinar cells and is essential for the
      maintenance of a differentiated acinar phenotype in the exocrine pancreas in
      vivo. In contrast, such abnormalities were not observed in the liver. Additional
      abnormalities in the pancreas included fibrosis, neoangiogenesis and mild
      macrophage infiltration, and these were associated with a marked up-regulation of
      TGF-beta expression in transgenic acinar cells. This transgenic model of targeted
      functional inactivation of TGF-beta signaling provides insights into mechanisms
      whereby loss of TGF-beta responsiveness might promote the carcinogenic process,
      both through direct effects on cell proliferation, and indirectly through up
      regulation of TGF-betas with associated paracrine effects on stromal
      compartments.

PMID- 9184211
TI  - Factors responsible for target site selection in Tn10 transposition: a role for
      the DDE motif in target DNA capture.
AB  - Tn10, like several other transposons, exhibits a marked preference for
      integration into particular target sequences. Such sequences are referred to as
      integration hotspots and have been used to define a consensus target site in Tn10
      transposition. We demonstrate that a Tn10 hotspot called HisG1, which was
      identified originally in vivo, also functions as an integration hotspot in vitro
      in a reaction where the HisG1 sequence is present on a short DNA oligomer. We use
      this in vitro system to define factors which are important for the capture of the
      HisG1 target site. We demonstrate that although divalent metal ions are not
      essential for HisG1 target capture, they greatly facilitate capture of a mutated
      HisG1 site. Analysis of catalytic transposase mutants further demonstrates that
      the DDE motif plays a critical role in 'divalent metal ion-dependent' target
      capture. Analysis of two other classes of transposase mutants, Exc+ Int- (which
      carry out transposon excision but not integration) and ATS (altered target
      specificity), demonstrates that while a particular ATS transposase binds HisG1
      mutants better than wild-type transposase, Exc+ Int- mutants are defective in
      HisG1 capture, further defining the properties of these classes of mutants.
      Possible mechanisms for the above observations are considered.

PMID- 9184210
TI  - Activation of the JNK pathway is essential for transformation by the Met
      oncogene.
AB  - The Met/Hepatocyte Growth Factor (HGF) receptor tyrosine kinase is oncogenically
      activated through a rearrangement that creates a hybrid gene Tpr-Met. The
      resultant chimeric p65(Tpr-Met) protein is constitutively phosphorylated on
      tyrosine residues in vivo and associates with a number of SH2-containing
      signaling molecules including the p85 subunit of PI-3 kinase and the Grb2 adaptor
      protein, which couples receptor tyrosine kinases to the Ras signaling pathway.
      Mutation of the binding site for Grb2 impairs the ability of Tpr-Met oncoprotein
      to transform fibroblasts, suggesting that the activation of the Ras/MAP kinase
      signaling pathway through Grb2 may be essential for cellular transformation. To
      test this hypothesis dominant-negative mutants of Grb2 with deletions of the SH3
      domains were introduced into Tpr-Met transformed fibroblasts. Cells
      overexpressing the mutants were found to be morphologically reverted and
      exhibited reduced growth in soft agar. Surprisingly, the Grb2 mutants blocked
      activation of the JNK/SAPK but not MAP kinase activity induced by the Tpr-Met
      oncoprotein. Additionally, cells expressing dominant-negative Grb2 mutants had
      reduced PI-3-kinase activity and dominant-negative mutants of Rac1 blocked both
      Tpr-Met-induced transformation and activation of JNK. These experiments reveal a
      novel link between Met and the JNK pathway, which is essential for transformation
      by this oncogene.

PMID- 9184212
TI  - Initiation of V(D)J recombination in vivo: role of recombination signal sequences
      in formation of single and paired double-strand breaks.
AB  - In V(D)J recombination, double-strand breaks (DSBs) are introduced at
      recombination signal sequences (RSSs) which consist of three distinct elements: a
      heptamer, a 12 or 23 nucleotide spacer and a nonamer. Efficient DSB formation
      requires a 12/23 RSS pair and occurs at both RSS in a temporally coupled fashion
      (coupled cleavage). It remains unknown which RSS elements are important for
      coupled cleavage. Furthermore, it has not been established whether some RSS
      components are critical only for cleavage in cis, with others mainly promoting
      cleavage in trans at the partner RSS. We investigated these questions by
      analyzing the effects of RSS mutations on the formation of DSBs in vivo. The
      abundance of DSBs in cis (at the mutant RSS) and in trans (at the consensus RSS)
      was determined using an established ligation-mediated PCR assay. We also
      developed a Southern blotting approach that allows the first direct measurement
      of dual and single RSS cleavage in vivo. Our results demonstrate that the
      heptamer, spacer and nonamer elements are all required for coupled cleavage in
      vivo. These studies also provide evidence for cleavage events involving a single
      RSS both in mutant substrates and in substrates containing a consensus 12/23 RSS
      pair.

PMID- 9184213
TI  - Stimulation of V(D)J cleavage by high mobility group proteins.
AB  - V(D)J recombination requires a pair of signal sequences with spacer lengths of 12
      and 23 bp between the conserved heptamer and nonamer elements. The RAG1 and RAG2
      proteins initiate the reaction by making double-strand DNA breaks at both
      signals, and must thus be able to operate on these two different spatial
      arrangements. We show that the DNA-bending proteins HMG1 and HMG2 stimulate
      cleavage and RAG protein binding at the 23 bp spacer signal. These findings
      suggest that DNA bending is important for bridging the longer spacer, and explain
      how a similar array of RAG proteins could accommodate a signal with either a 12
      or a 23 bp spacer. An additional effect of HMG proteins is to stimulate coupled
      cleavage greatly when both signal sequences are present, suggesting that these
      proteins also aid the formation of a synaptic complex.

PMID- 9184214
TI  - The NTPase/helicase activities of Drosophila maleless, an essential factor in
      dosage compensation.
AB  - Drosophila maleless (mle) is required for X chromosome dosage compensation and is
      essential for male viability. Maleless protein (MLE) is highly homologous to
      human RNA helicase A and the bovine counterpart of RNA helicase A, nuclear
      helicase II. In this report, we demonstrate that MLE protein, overexpressed and
      purified from Sf9 cells infected with recombinant baculovirus, possesses RNA/DNA
      helicase, adenosine triphosphatase (ATPase) and single-stranded (ss) RNA/ssDNA
      binding activities, properties identical to RNA helicase A. Using site-directed
      mutagenesis, we created a mutant of MLE (mle-GET) that contains a glutamic acid
      in place of lysine in the conserved ATP binding site A. In vitro biochemical
      analysis showed that this mutation abolished both NTPase and helicase activities
      of MLE but affected the ability of MLE to bind to ssRNA, ssDNA and guanosine
      triphosphate (GTP) less severely. In vivo, mle-GET protein could still localize
      to the male X chromosome coincidentally with the male-specific lethal-1 protein,
      MSL-1, but failed to complement mle1 mutant males. These results indicate that
      the NTPase/helicase activities are essential functions of MLE for dosage
      compensation, perhaps utilized for chromatin remodeling of X-linked genes.

PMID- 9184215
TI  - rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes,
      is required for reversible S phase arrest.
AB  - In eukaryotic cells, S phase can be reversibly arrested by drugs that inhibit DNA
      synthesis or DNA damage. Here we show that recovery from such treatments is under
      genetic control and is defective in fission yeast rqh1 mutants. rqh1+, previously
      known as hus2+, encodes a putative DNA helicase related to the Escherichia coli
      RecQ helicase, with particular homology to the gene products of the human BLM and
      WRN genes and the Saccharomyces cerevisiae SGS1 gene. BLM and WRN are mutated in
      patients with Bloom's syndrome and Werner's syndrome respectively. Both syndromes
      are associated with genomic instability and cancer susceptibility. We show that,
      like BLM and SGS1, rqh1+ is required to prevent recombination and that in fission
      yeast suppression of inappropriate recombination is essential for reversible S
      phase arrest.

PMID- 9184216
TI  - Regulation of B-type cyclin proteolysis by Cdc28-associated kinases in budding
      yeast.
AB  - In budding yeast, stability of the mitotic B-type cyclin Clb2 is tightly cell
      cycle-regulated. B-type cyclin proteolysis is initiated during anaphase and
      persists throughout the G1 phase. Cln-Cdc28 kinase activity at START is required
      to repress B-type cyclin-specific proteolysis. Here, we show that Clb-dependent
      kinases, when expressed during G1, are also capable of repressing the B-type
      cyclin proteolysis machinery. Furthermore, we find that inactivation of Cln- and
      Clb-Cdc28 kinases is sufficient to trigger Clb2 proteolysis and sister-chromatid
      separation in G2/M phase-arrested cells, where the B-type cyclin-specific
      proteolysis machinery is normally inactive. Our results suggest that Cln- and Clb
      dependent kinases are both capable of repressing B-type cyclin-specific
      proteolysis and that they are required to maintain the proteolysis machinery in
      an inactive state in S and G2/M phase-arrested cells. We propose that in yeast,
      as cells pass through START, Cln-Cdc28-dependent kinases inactivate B-type cyclin
      proteolysis. As Cln-Cdc28-dependent kinases decline during G2, Clb-Cdc28
      dependent kinases take over this role, ensuring that B-type cyclin proteolysis is
      not activated during S phase and early mitosis.

PMID- 9184217
TI  - Cell-free synthesis and assembly of connexins into functional gap junction
      membrane channels.
AB  - Several different gap junction channel subunit isotypes, known as connexins, were
      synthesized in a cell-free translation system supplemented with microsomal
      membranes to study the mechanisms involved in gap junction channel assembly.
      Previous results indicated that the connexins were synthesized as membrane
      proteins with their relevant transmembrane topology. An integrated biochemical
      and biophysical analysis indicated that the connexins assembled specifically with
      other connexin subunits. No interactions were detected between connexin subunits
      and other co-translated transmembrane proteins. The connexins that were
      integrated into microsomal vesicles assembled into homo- and hetero-oligomeric
      structures with hydrodynamic properties of a 9S particle, consistent with the
      properties reported for hexameric gap junction connexons derived from gap
      junctions in vivo. Further, cell-free assembled homo-oligomeric connexons
      composed of beta1 or beta2 connexin were reconstituted into synthetic lipid
      bilayers. Single channel conductances were recorded from these bilayers that were
      similar to those measured for these connexons produced in vivo. Thus, this is the
      first direct evidence that the synthesis and assembly of a gap junction connexon
      can take place in microsomal membranes. Finally, the cell-free system has been
      used to investigate the properties of alpha1, beta1 and beta2 connexin to
      assemble into hetero-oligomers. Evidence has been obtained for a selective
      interaction between individual connexin isotypes and that a signal determining
      the potential hetero-oligomeric combinations of connexin isotypes may be located
      in the N-terminal sequence of the connexins.

PMID- 9184218
TI  - Modulation of bacterial entry into epithelial cells by association between
      vinculin and the Shigella IpaA invasin.
AB  - Shigella flexneri is the causative agent of bacillary dysentery in humans.
      Shigella invasion of epithelial cells is characterized by cytoskeletal
      rearrangements and formation of cellular projections engulfing the bacterium in a
      macropinocytic process. We show here that vinculin, a protein involved in linking
      actin filaments to the plasma membrane, is a direct target of Shigella during
      cell invasion. IpaA, a Shigella protein secreted upon cell contact, rapidly
      associates with vinculin during bacterial invasion. Although defective for cell
      entry, an ipaA mutant is still able to induce foci of actin polymerization, but
      differs from wild-type Shigella in its ability to recruit vinculin and alpha
      actinin. Presumably, IpaA-vinculin interaction initiates the formation of focal
      adhesion-like structures required for efficient invasion.

PMID- 9184219
TI  - Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial
      protein tyrosine phosphatase that translocates into mammalian cells and targets
      focal adhesions.
AB  - A number of pathogenic bacteria utilize type III secretion pathways to
      translocate virulence proteins into host eukaryotic cells. We identified a host
      target of YopH, a protein tyrosine phosphatase that is translocated into
      mammalian cells by Yersiniae. A catalytically inactive 'substrate-trapping'
      mutant, YopHC403S, was used as a probe to determine where YopH substrates
      localize in eukaryotic cells. Immunofluorescence microscopy demonstrated that
      YopHC403S localized to focal adhesions in human epithelial cells infected with Y.
      pseudotuberculosis. YopHC403S stabilized focal adhesions, as shown by its
      dominant-negative effect on focal adhesion disassembly mediated by YopE, a
      translocated protein which disrupts actin stress fibers. Conversely, YopH
      destabilized focal adhesions, even in the absence of YopE, as shown by loss of
      phosphotyrosine staining. Immunoprecipitation revealed that YopHC403S was trapped
      in a complex with a hyperphosphorylated 125-135 kDa protein, identified by
      immunoblotting as the focal adhesion protein p130Cas. YopHC403S bound directly to
      p130Cas in a phosphotyrosine-dependent manner in vitro. Translocation of YopH
      into cells plated on fibronectin resulted in rapid and selective
      dephosphorylation of p130Cas. These results demonstrate that YopH targets focal
      adhesions in host cells and that p130Cas, a docking protein for multiple SH2
      domains, is a direct substrate of this enzyme in vivo.

PMID- 9184220
TI  - Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which
      interact with profilin and regulate actin cytoskeleton in Saccharomyces
      cerevisiae.
AB  - The RHO1 gene encodes a homologue of mammalian RhoA small G-protein in the yeast
      Saccharomyces cerevisiae. Rho1p is required for bud formation and is localized at
      a bud tip or a cytokinesis site. We have recently shown that Bni1p is a potential
      target of Rho1p. Bni1p shares the FH1 and FH2 domains with proteins involved in
      cytokinesis or establishment of cell polarity. In S. cerevisiae, there is an open
      reading frame (YIL159W) which encodes another protein having the FH1 and FH2
      domains and we have named this gene BNR1 (BNI1 Related). Bnr1p interacts with
      another Rho family member, Rho4p, but not with Rho1p. Disruption of BNI1 or BNR1
      does not show any deleterious effect on cell growth, but the bni1 bnr1 mutant
      shows a severe temperature-sensitive growth phenotype. Cells of the bni1 bnr1
      mutant arrested at the restrictive temperature are deficient in bud emergence,
      exhibit a random distribution of cortical actin patches and often become
      multinucleate. These phenotypes are similar to those of the mutant of PFY1, which
      encodes profilin, an actin-binding protein. Moreover, yeast two-hybrid and
      biochemical studies demonstrate that Bni1p and Bnr1p interact directly with
      profilin at the FH1 domains. These results indicate that Bni1p and Bnr1p are
      potential targets of the Rho family members, interact with profilin and regulate
      the reorganization of actin cytoskeleton.

PMID- 9184221
TI  - Distinct catalytic roles of the SecYE, SecG and SecDFyajC subunits of preprotein
      translocase holoenzyme.
AB  - Escherichia coli preprotein translocase contains a membrane-embedded trimeric
      complex of SecY, SecE and SecG (SecYEG) and the peripheral SecA protein. SecYE is
      the conserved functional 'core' of the SecYEG complex. Although sufficient to
      provide sites for high-affinity binding and membrane insertion of SecA, and for
      its activation as a preprotein-dependent ATPase, SecYE has only very low capacity
      to support translocation. The proteins encoded by the secD operon--SecD, SecF and
      YajC--also form an integral membrane heterotrimeric complex (SecDFyajC). Physical
      and functional studies show that these two trimeric complexes are associated to
      form SecYEGDFyajC, the hexameric integral membrane domain of the preprotein
      translocase 'holoenzyme'. Either SecG or SecDFyajC can support the translocation
      activity of SecYE by facilitating the ATP-driven cycle of SecA membrane insertion
      and de-insertion at different stages of the translocation reaction. Our findings
      show that each of the prokaryote-specific subunits (SecA, SecG and SecDFyajC)
      function together to promote preprotein movement at the SecYE core of the
      translocase.

PMID- 9184222
TI  - Novel Golgi to vacuole delivery pathway in yeast: identification of a sorting
      determinant and required transport component.
AB  - More than 40 vacuolar protein sorting (vps) mutants have been identified which
      secrete proenzyme forms of soluble vacuolar hydrolases to the cell surface. A
      subset of these mutants has been found to show selective defects in the sorting
      of two vacuolar membrane proteins. Under non-permissive conditions, vps45tsf
      (SEC1 homolog) and pep12/vps6tsf (endosomal t-SNARE) mutants efficiently sort
      alkaline phosphatase (ALP) to the vacuole while multiple soluble vacuolar
      proteins and the membrane protein carboxypeptidase yscS (CPS) are no longer
      delivered to the vacuole. Vacuolar localization of ALP in these mutants does not
      require transport to the plasma membrane followed by endocytic uptake, as double
      mutants of pep12tsf and vps45tsf with sec1 and end3 sort and mature ALP at the
      non-permissive temperature. Given the demonstrated role of t-SNAREs such as
      Pep12p in transport vesicle recognition, our results indicate that ALP and CPS
      are packaged into distinct transport intermediates. Consistent with ALP following
      an alternative route to the vacuole, isolation of a vps41tsf mutant revealed that
      at non-permissive temperature ALP is mislocalized while vacuolar delivery of CPS
      and CPY is maintained. A series of domain-swapping experiments was used to define
      the sorting signal that directs selective packaging and transport of ALP. Our
      data demonstrate that the amino-terminal 16 amino acid portion of the ALP
      cytoplasmic tail domain contains a vacuolar sorting signal which is responsible
      for the active recognition, packaging and transport of ALP from the Golgi to the
      vacuole via a novel delivery pathway.

PMID- 9184223
TI  - Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH
      kinase and protein kinase B/Akt cellular survival pathway.
AB  - Upon detachment from the extracellular matrix, epithelial cells enter into
      programmed cell death, a phenomenon known as anoikis, ensuring that they are
      unable to survive in an inappropriate location. Activated ras oncogenes protect
      cells from this form of apoptosis. The nature of the survival signals activated
      by integrin engagement and usurped by oncogenic Ras are unknown: here we show
      that in both cases phosphoinositide 3-OH kinase (PI 3-kinase), but not Raf,
      mediates this protection, acting through protein kinase B/Akt (PKB/Akt).
      Constitutively activated PI 3-kinase or PKB/Akt block anoikis, while inhibition
      of PI 3-kinase abrogates protection by Ras, but not PKB/Akt. Inhibition of either
      PI 3-kinase or PKB/Akt induces apoptosis in adherent epithelial cells. Attachment
      of cells to matrix leads to rapid elevation of the levels of PI 3-kinase lipid
      products and PKB/Akt activity, both of which remain high in Ras-transformed cells
      even in suspension. PI 3-kinase acting through PKB/Akt is therefore implicated as
      a key mediator of the aberrant survival of Ras-transformed epithelial cells in
      the absence of attachment, and mediates matrix-induced survival of normal
      epithelial cells.

PMID- 9184224
TI  - FLICE is activated by association with the CD95 death-inducing signaling complex
      (DISC).
AB  - Upon activation, the apoptosis-inducing cell membrane receptor CD95 (APO-1/Fas)
      recruits a set of intracellular signaling proteins (CAP1-4) into a death-inducing
      signaling complex (DISC). In the DISC, CAP1 and CAP2 represent FADD/MORT1. CAP4
      was identified recently as an ICE-like protease, FLICE, with two death effector
      domains (DED). Here we show that FLICE binds to FADD through its N-terminal DED.
      This is an obligatory step in CD95 signaling detected in the DISC of all CD95
      sensitive cells tested. Upon prolonged triggering of CD95 with agonistic
      antibodies all cytosolic FLICE gets proteolytically activated. Physiological
      FLICE cleavage requires association with the DISC and occurs by a two-step
      mechanism. Initial cleavage generates a p43 and a p12 fragment further processed
      to a p10 fragment. Subsequent cleavage of the receptor-bound p43 results in
      formation of the prodomain p26 and the release of the active site-containing
      fragment p18. Activation of FLICE is blocked by the peptide inhibitors zVAD-fmk,
      zDEVD-fmk and zIETD-fmk, but not by crmA or Ac-YVAD-CHO. Taken together, our data
      indicate that FLICE is the first in a cascade of ICE-like proteases activated by
      CD95 and that this activation requires a functional CD95 DISC.

PMID- 9184225
TI  - Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE.
AB  - Cysteine proteases of the ICE/CED-3 family (caspases) are required for the
      execution of programmed cell death (PCD) in a wide range of multicellular
      organisms. Caspases are implicated in the execution of apoptosis in Drosophila
      melanogaster by the observation that expression of baculovirus p35, a caspase
      inhibitor, blocks cell death in vivo in Drosophila. We report here the
      identification and characterization of drICE, a D. melanogaster caspase. We show
      that overexpression of drICE sensitizes Drosophila cells to apoptotic stimuli and
      that expression of an N-terminally truncated form of drICE rapidly induces
      apoptosis in Drosophila cells. Induction of apoptosis by rpr overexpression or by
      cycloheximide or etoposide treatment of Drosophila cells results in proteolytic
      processing of drICE. We further show that drICE is a cysteine protease that
      cleaves baculovirus p35 and Drosophila lamin DmO in vitro and that drICE is
      expressed at all the stages of Drosophila development at which PCD can be
      induced. Taken together, these results strongly argue that drICE is an apoptotic
      caspase that acts downstream of rpr. drICE is therefore the first unequivocal
      link between the molecular machinery of Drosophila cell death and the conserved
      machinery of Caenorhabditis elegans and vertebrates. Identification of drICE
      should facilitate the elucidation of upstream regulators and downstream targets
      of caspases by genetic screening.

PMID- 9184226
TI  - Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger
      protein expressed in the pituitary gland and the brain.
AB  - The proliferation rate of a cell population reflects a balance between cell
      division, cell cycle arrest, differentiation and apoptosis. The regulation of
      these processes is central to development and tissue homeostasis, whereas
      dysregulation may lead to overt pathological outcomes, notably cancer and
      neurodegenerative disorders. We report here the cloning of a novel zinc finger
      protein which regulates apoptosis and cell cycle arrest and was accordingly named
      Zac1. In vitro Zac1 inhibited proliferation of tumor cells, as evidenced by
      measuring colony formation, growth rate and cloning in soft agar. In vivo Zac1
      abrogated tumor formation in nude mice. The antiproliferative activity of Zac1
      was due to induction of extensive apoptosis and of G1 arrest, which proceeded
      independently of retinoblastoma protein and of regulation of p21(WAF1/Cip1),
      p27Kip1, p57Kip2 and p16INK4a expression. Zac1-mediated apoptosis was unrelated
      to cell cycle phase and G1 arrest was independent of apoptosis, indicating
      separate control of apoptosis and cell cycle arrest. Zac1 is thus the first gene
      besides p53 which concurrently induces apoptosis and cell cycle arrest.

PMID- 9184227
TI  - Recombination between DNA repeats in yeast hpr1delta cells is linked to
      transcription elongation.
AB  - The induction of recombination by transcription activation has been documented in
      prokaryotes and eukaryotes. Unwinding of the DNA duplex, disruption of chromatin
      structure or changes in local supercoiling associated with transcription can be
      indirectly responsible for the stimulation of recombination. Here we provide
      genetic and molecular evidence for a specific mechanism of stimulation of
      recombination by transcription. We show that the induction of deletions between
      repeats in hpr1delta cells of Saccharomyces cerevisiae is linked to transcription
      elongation. Molecular analysis of different direct repeat constructs reveals that
      deletions induced by hpr1delta are specific for repeat constructs in which
      transcription initiating at an external promoter traverses particular regions of
      the DNA flanked by the repeats. Transcription becomes HPR1 dependent when
      elongating through such regions. Both the induction of deletions and the HPR1
      dependence of transcription were abolished when a strong terminator was used to
      prevent transcription from proceeding through the DNA region flanked by the
      repeats. In contrast to previously reported cases of transcription-induced
      recombination, there was no correlation between high levels of transcripts and
      high levels of recombination. Our study provides evidence that direct repeat
      recombination can be induced by transcriptional elongation.

PMID- 9184229
TI  - Expression of MHC class II molecules in different cellular and functional
      compartments is controlled by differential usage of multiple promoters of the
      transactivator CIITA.
AB  - The highly complex pattern of expression of major histocompatibility complex
      class II (MHC-II) molecules determines both the immune repertoire during
      development and subsequently the triggering and the control of immune responses.
      These distinct functions result from cell type-restricted expression,
      developmental control and either constitutive or inducible expression of MHC-II
      genes. Yet, in these various situations, MHC-II gene expression is always under
      the control of a unique transactivator, CIITA. Here we show that the CIITA gene
      is controlled by several distinct promoters, two of which direct specific
      constitutive expression in dendritic cells and B lymphocytes respectively, while
      another mediates gamma-interferon-induced expression. Thus the cellular, temporal
      and functional diversity of MHC-II expression is ultimately controlled by
      differential activation of different promoters of a single transactivator gene.
      This provides novel experimental tools to dissect compartment-specific gain or
      loss of MHC-II function in vivo.

PMID- 9184228
TI  - Purification of a Tat-associated kinase reveals a TFIIH complex that modulates
      HIV-1 transcription.
AB  - The Tat protein is a transcriptional activator which is required for efficient
      human immunodeficiency virus 1 (HIV-1) gene expression Tat stimulates HIV-1
      transcriptional elongation by increasing the processivity of RNA polymerase II.
      To address whether Tat-mediated effects on HIV-1 gene expression are due to
      modulation in the phosphorylation of the RNA polymerase II C-terminal domain
      (CTD), we developed a purification protocol to identify cellular kinases that are
      capable of binding to Tat and hyperphosphorylating the RNA polymerase II CTD. A
      600 kDa protein complex with these properties was isolated, and specific
      components were identified using peptide microsequence analysis. This analysis
      indicated that proteins comprising the multi-subunit TFIIH complex, in addition
      to several novel factors, were associated with Tat using both in vitro and in
      vivo analysis. The Tat-associated kinase bound to the activation domain of Tat,
      and its ability to hyperphosphorylate RNA polymerase II was markedly stimulated
      by Tat. Furthermore, the addition of the Tat-associated kinase to in vitro
      transcription assays stimulated the ability of Tat to activate HIV-1
      transcription. These results define a cellular kinase complex whose activity is
      modulated by Tat to result in activation of HIV-1 trancription.

PMID- 9184230
TI  - The promoter context is a decisive factor in establishing selective
      responsiveness to nuclear class II receptors.
AB  - The vigorous retinoic acid (RA)-dependent activation of the retinoic acid
      receptor beta2 (RARbeta2) gene in embryonal carcinoma (EC) cells is mediated by
      retinoid receptor heterodimers (RXR-RAR) binding to RAREs that are closely
      positioned to the TATA box and an EC cell-specific co-factor activity termed E1A
      LA. Using a series of direct repeat (DR) elements, we now show that positioning
      RXR-RAR in close proximity to the basal transcription machinery assembled on the
      TATA box is decisive in RA responsiveness in EC cells. Notably, a DR1 element
      functions predominantly as an RAR-responsive element when placed in the context
      of the RARbeta2 promoter. Moreover, DR3 and DR4 elements which mediate vitamin D3
      and thyroid hormone responses, respectively, in other contexts, are converted to
      exclusive RAR response elements when placed in the RARbeta2 promoter and EC cell
      context. In differentiated cells, the adenovirus E1A(13S) protein is required to
      achieve high level RA activation through all of the different DR elements placed
      in the RARbeta2 context, suggesting that the molecular bridging function of E1A
      LA [E1A(13S)] is essential to redefining response element specificity. Finally,
      we show that the arrangement of cis-acting elements as present in the RARbeta2
      promoter is not crucial, but rather the close positioning of the RAREs to the
      TATA. We conclude that the identity of a given cis-acting element is defined not
      only by its affinity for the transactivator, but also by the context in which it
      is placed, as well as the cell type in which the transactivator is expressed.

PMID- 9184231
TI  - The N-terminal fingers of chicken GATA-2 and GATA-3 are independent sequence
      specific DNA binding domains.
AB  - The GATA family of vertebrate DNA binding regulatory proteins are expressed in
      diverse tissues and at different times of development. However, the DNA binding
      regions of these proteins possess considerable homology and recognize a rather
      similar range of DNA sequence motifs. DNA binding is mediated through two
      domains, each containing a zinc finger. Previous results have led to the
      conclusion that although in some cases the N-terminal finger can contribute to
      specificity and strength of binding, it does not bind independently, whereas the
      C-terminal finger is both necessary and sufficient for binding. Here we show that
      although this is true for the N-terminal finger of GATA-1, those of GATA-2 and
      GATA-3 are capable of strong independent binding with a preference for the motif
      GATC. Binding requires the presence of two basic regions located on either side
      of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal
      finger probably accounts for its inability to bind. The combination of a single
      finger and two basic regions is a new variant of a motif that has been previously
      found in the binding domains of other finger proteins. Our results suggest that
      the DNA binding properties of the N-terminal finger may help distinguish GATA-2
      and GATA-3 from GATA-1 and the other GATA family members in their selective
      regulatory roles in vivo.

PMID- 9184232
TI  - hairy mediates dominant repression in the Drosophila embryo.
AB  - hairy encodes a bHLH repressor that regulates several developmental processes in
      Drosophila, including embryonic segmentation and neurogenesis. Segmentation
      repressors such as Kruppel and knirps have been shown to function over short
      distances, less than 50-100 bp, to inhibit or quench closely linked upstream
      activators. This mode of repression permits multiple enhancers to work
      independently of one another within a modular promoter. Here, we employ a
      transgenic embryo assay to present evidence that hairy acts as a dominant
      repressor, which can function over long distances to block multiple enhancers.
      hairy is shown to repress a heterologous enhancer, the rhomboid NEE, when bound 1
      kb from the nearest upstream activator. Moreover, the binding of hairy to a
      modified NEE leads to the repression of both the NEE and a distantly linked
      mesoderm-specific enhancer within a synthetic modular promoter. Additional
      evidence that hairy is distinct from previously characterized embryonic
      repressors stems from the analysis of the gypsy insulator DNA. This insulator
      selectively blocks the hairy repressor, but not the linked activators, within a
      modified NEE. We compare hairy with previously characterized repressors and
      discuss the consequences of short-range and long-range repression in development.

PMID- 9184233
TI  - Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes
      with Max, binds a non-canonical E box and acts as a transcriptional repressor.
AB  - Proteins of the Myc and Mad family are involved in transcriptional regulation and
      mediate cell differentiation and proliferation. These molecules share a basic
      helix-loop-helix leucine zipper domain (bHLHZip) and bind DNA at the E box
      (CANNTG) consensus by forming heterodimers with Max. We report the isolation,
      characterization and mapping of a human gene and its mouse homolog encoding a new
      member of this family of proteins, named Rox. Through interaction mating and
      immunoprecipitation techniques, we demonstrate that Rox heterodimerizes with Max
      and weakly homodimerizes. Interestingly, bandshift assays demonstrate that the
      Rox-Max heterodimer shows a novel DNA binding specificity, having a higher
      affinity for the CACGCG site compared with the canonical E box CACGTG site.
      Transcriptional studies indicate that Rox represses transcription in both human
      HEK293 cells and yeast. We demonstrate that repression in yeast is through
      interaction between the N-terminus of the protein and the Sin3 co-repressor, as
      previously shown for the other Mad family members. ROX is highly expressed in
      quiescent fibroblasts and expression markedly decreases when cells enter the cell
      cycle. Moreover, ROX expression appears to be induced in U937 myeloid leukemia
      cells stimulated to differentiate with 12-O-tetradecanoylphorbol-13-acetate. The
      identification of a novel Max-interacting protein adds an important piece to the
      puzzle of Myc/Max/Mad coordinated action and function in normal and pathological
      situations. Furthermore, mapping of the human gene to chromosome 17p13.3 in a
      region that frequently undergoes loss of heterozygosity in a number of
      malignancies, together with the biochemical and expression features, suggest
      involvement of ROX in human neoplasia.

PMID- 9184234
TI  - The transcription activation domains of Fos and Jun induce DNA bending through
      electrostatic interactions.
AB  - Transcription factor-induced DNA bending is essential for the assembly of active
      transcription complexes at many promoters. However, most eukaryotic transcription
      regulatory proteins have modular DNA-binding and activation domains, which
      appeared to exclude DNA bending as a mechanism of transcription activation by
      these proteins. We show that the transcription activation domains of Fos and Jun
      induce DNA bending. In chimeric proteins, the transcription activation domains
      induce DNA bending independent of the DNA-binding domains. DNA bending by the
      chimeric proteins is directed diametrically away from the transcription
      activation domains. Therefore, the opposite directions of DNA bending by Fos and
      Jun are caused, in part, by the opposite locations of the transcription
      activation domains relative to the DNA-binding domains in these proteins. DNA
      bending is reduced in the presence of multivalent cations, indicating that
      electrostatic interactions contribute to DNA bending by Fos and Jun.
      Consequently, regions outside the minimal DNA-binding domain can influence DNA
      structure, and may thereby contribute to the architectural reorganization of the
      promoter region required for gene activation.

PMID- 9184235
TI  - DNA bending by Fos-Jun and the orientation of heterodimer binding depend on the
      sequence of the AP-1 site.
AB  - Interactions among transcription factors that bind to separate promoter elements
      depend on distortion of DNA structure and the appropriate orientation of
      transcription factor binding to allow juxtaposition of complementary structural
      motifs. We show that Fos and Jun induce distinct DNA bends at different binding
      sites, and that heterodimers bind to AP-1 sites in a preferred orientation.
      Sequences on each side of the consensus AP-1 recognition element have independent
      effects on DNA bending. A single base pair substitution outside the sequences
      contacted in the X-ray crystal structure alters DNA bending. Substitution of
      sequences flanking the AP-1 site has converse effects on DNA bending in opposite
      directions, suggesting that the extent of DNA bending by Fos and Jun is
      determined in part by the anisotropic bendability of sequences flanking the AP-1
      site. DNA bending by Fos and Jun, and the orientation of heterodimer binding are
      interrelated. Reversal of the orientation of heterodimer binding causes a shift
      in the direction of DNA bending. The preferred orientation of heterodimer binding
      is determined both by contacts between a conserved arginine in the basic region
      of Fos and the central asymmetric guanine as well as the structure of sequences
      flanking the AP-1 site. Consequently, the structural adaptability of the Fos-Jun
      AP1 complex may contribute to its functional versatility at different promoters.

PMID- 9184236
TI  - Factor requirements for transcription in the Archaeon Sulfolobus shibatae.
AB  - Archaea (archaebacteria) constitute a domain of life that is distinct from
      Bacteria (eubacteria) and Eucarya (eukaryotes). Although archaeal cells share
      many morphological features with eubacteria, their transcriptional apparatus is
      more akin to eukaryotic RNA polymerases I, II and III than it is to eubacterial
      transcription systems. Thus, in addition to possessing a 10 subunit RNA
      polymerase and a homologue of the TATA-binding protein (TBP), Archaea possess a
      polypeptide termed TFB that is homologous to eukaryotic TFIIB. Here, we
      investigate the factor requirements for transcription of several promoters of the
      archaeon Sulfolobus shibatae and its associated virus SSV. Through in vitro
      transcription and immunodepletion, we demonstrate that S. shibatae TBP, TFB and
      RNA polymerase are not complexed tightly with one another and that each is
      required for efficient transcription of all promoters tested. Furthermore, full
      transcription is restored by supplementing respective depleted extracts with
      recombinant TBP or TFB, indicating that TBP-associated factors or TFB-associated
      factors are not required. Indeed, gel-filtration suggests that Sulfolobus TBP and
      TFB are not associated stably with other proteins. Finally, all promoters
      analysed are transcribed accurately and efficiently in an in vitro system
      comprising recombinant TBP and TFB, together with essentially homogeneous
      preparation of RNA polymerase. Transcription in Archaea is therefore
      fundamentally homologous to that in eukaryotes, although factor requirements
      appear to be much less complex.

PMID- 9184237
TI  - The integration of nitrogen and carbon catabolite repression in Aspergillus
      nidulans requires the GATA factor AreA and an additional positive-acting element,
      ADA.
AB  - The expression of the structural genes of the proline utilization cluster of
      Aspergillus nidulans is repressed efficiently only when both repressing carbon
      and nitrogen sources are present. Two hypotheses can account for this fact. One
      is a direct or indirect competition mechanism between the positive-acting AreA
      GATA factor, mediating nitrogen metabolite repression, and the negative-acting
      CreA protein, mediating carbon catabolite repression. The second is to propose
      that CreA prevents the binding or activity of another, as yet unidentified,
      positive-acting factor, here called ADA. We show the second possibility to be the
      correct one, and we localize the new positive cis-acting element within 290 bp of
      the prnD-prnB divergent promoter.

PMID- 9184238
TI  - Identification of structural elements critical for inter-domain interactions in a
      group II self-splicing intron.
AB  - Thus far, conventional biophysical techniques, such as NMR spectroscopy or X-ray
      crystallography, allow the determination, at atomic resolution, of only
      structural domains of large RNA molecules such as group I introns. Determination
      of their overall spatial organization thus still relies on modeling. This
      requires that a relatively high number of tertiary interactions are defined in
      order to get sufficient topological constraints. Here, we report the use of a
      modification interference assay to identify structural elements involved in
      interdomain interactions. We used this technique, in a group II intron, to
      identify the elements involved in the interactions between domain V and the rest
      of the molecule. Domain V contains many of the active site components of these
      ribozymes. In addition to a previously identified 11 nucleotide motif involved in
      the binding of the domain V terminal GAAA tetraloop, a small number of elements
      were shown to be essential for domain V binding. In particular, we show that
      domain III is specifically required for the interaction with sequences
      encompassing the conserved 2 nucleotide bulge of domain V.

PMID- 9184239
TI  - The human RNA 3'-terminal phosphate cyclase is a member of a new family of
      proteins conserved in Eucarya, Bacteria and Archaea.
AB  - RNA 3'-terminal phosphate cyclase catalyses the ATP-dependent conversion of the
      3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA. The
      physiological function of the cyclase is not known, but the enzyme could be
      involved in the maintenance of cyclic ends in tRNA splicing intermediates or in
      the cyclization of the 3' end of U6 snRNA. In this work, we describe cloning of
      the human cyclase cDNA. The purified bacterially overexpressed protein underwent
      adenylylation in the presence of [alpha-32P]ATP and catalysed cyclization of the
      3'-terminal phosphate in different RNA substrates, consistent with previous
      findings. Comparison of oligoribonucleotides and oligodeoxyribonucleotides of
      identical sequence demonstrated that the latter are approximately 500-fold poorer
      substrates for the enzyme. In Northern analysis, the cyclase was expressed in all
      analysed mammalian tissues and cell lines. Indirect immunofluorescence, performed
      with different transfected mammalian cell lines, showed that this protein is
      nuclear, with a diffuse nucleoplasmic localization. The sequence of the human
      cyclase has no apparent motifs in common with any proteins of known function.
      However, inspection of the databases identified proteins showing strong
      similarity to the enzyme, originating from as evolutionarily distant organisms as
      yeast, plants, the bacterium Escherichia coli and the archaeon Methanococcus
      jannaschii. The overexpressed E. coli protein has cyclase activity similar to
      that of the human enzyme. The conservation of the RNA 3'-terminal phosphate
      cyclase among Eucarya, Bacteria and Archaea argues that the enzyme performs an
      important function in RNA metabolism.

PMID- 9184240
TI  - Rescuing an essential enzyme-RNA complex with a non-essential appended domain.
AB  - Certain protein-RNA complexes, such as synthetase-tRNA complexes, are essential
      for cell survival. These complexes are formed with a precise molecular fit along
      the interface of the reacting partners, and mutational analyses have shown that
      amino acid or nucleotide substitutions at the interface can be used to disrupt
      functional or repair non-functional complexes. In contrast, we demonstrate here a
      feature of a eukaryote system that rescues a disrupted complex without directly
      re-engineering the interface. The monomeric yeast Saccharomyces cerevisiae
      glutaminyl-tRNA synthetase, like several other class I eukaryote tRNA
      synthetases, has an active-site-containing 'body' that is closely homologous to
      its Escherichia coli relative, but is tagged at its N-terminus with a novel and
      dispensable appended domain whose role has been obscure. Because of differences
      between the yeast and E. coli glutamine tRNAs that presumably perturb the enzyme
      tRNA interface, E. coli glutaminyl-tRNA synthetase does not charge yeast tRNA.
      However, linking the novel appended domain of the yeast to the E. coli enzyme
      enabled the E. coli protein to function as a yeast enzyme, in vitro and in vivo.
      The appended domain appears to contribute an RNA interaction that compensates for
      weak or poor complex formation. In eukaryotes, extra appended domains occur
      frequently in these proteins. These domains may be essential when there are
      conditions that would otherwise weaken or disrupt formation of a critical RNA
      protein complex. They may also be adapted for other, specialized RNA-related
      functions in specific instances.

PMID- 9184241
TI  - Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel mutations in
      the calmodulin-like repeats of cartilage oligomeric matrix protein.
AB  - A child with a mild form of pseudoachondroplasia was heterozygous for a deletion
      of 12 nucleotides from exon 10 of the cartilage oligomeric matrix protein (COMP)
      gene. It resulted in the deletion of valine 513 to lysine 516 from the eighth
      calmodulin-like repeat of COMP monomers. A child with the Fairbank's type of
      multiple epiphyseal dysplasia was also heterozygous for a COMP mutation. It
      substituted cysteine 371 by serine in the fourth calmodulin-like repeat. Both
      mutations were likely to alter the conformation and calcium binding of the mutant
      COMP protein chains. These findings support the proposal that deletions and
      insertions within the calmodulin-like domain produce pseudoachondroplasia, while
      amino acid substitutions with this domain may produce either pseudoachondroplasia
      or multiple epiphyseal dysplasia.

PMID- 9184242
TI  - Analysis of the (CAG)n repeat causing Huntington's disease in a Mexican
      population.
AB  - We investigated the allele distribution of the polymorphic (CAG)n repeat in the
      IT15 gene in 96 normal subjects from the Mexican population and 83 unrelated
      patients with Huntington's disease. Our results show that the size distributions
      of normal and affected alleles do not overlap. Normal alleles range from 13 to 32
      triplets, with 18 being the most frequent allele, while HD alleles contain 37 to
      76 repeats with 42 being the most frequent. One allele in the range of
      intermediate alleles was found (32 repeats) in a normal subject. The juvenile
      onset cases in this study are associated with an expansion greater than 49
      repeats. In the available parent-offspring pairs, paternal alleles show
      instability with an expansion of 28 repeats in one case.

PMID- 9184243
TI  - Evaluation of an aspartame loading test for the detection of heterozygotes for
      classical phenylketonuria.
AB  - Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal
      recessive inheritance characterized by the accumulation of phenylalanine (Phe) in
      tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed
      for the detection of PKU heterozygotes based on the determination of plasma Phe
      and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe2/Tyr ratios and
      on the use of discriminant functions. The objective of the present study was to
      test the value of loading with aspartame (a sweetener consisting of Phe,
      aspartate and methanol) for the identification of PKU carriers. The study was
      conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were
      collected (under fasting conditions and 30 min after the loading) for
      fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe2/Tyr values were
      higher in heterozygotes, whereas Tyr was higher in controls in both situations
      investigated. Linear discriminant function was considered to be the best
      parameter for differentiation of the individuals in the two groups. Under the
      conditions employed in the present study, aspartame loading did not show any
      advantages in discriminating between PKU carriers and normal individuals when
      compared to the same analysis performed under fasting conditions.

PMID- 9184245
TI  - The cholesteryl ester transfer protein (CETP) locus as a candidate gene in
      abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a relatively common disease of the elderly
      presenting as progressive dilatation of the abdominal aorta. The condition shows
      a pronounced tendency to cluster in families, indicating a genetic component in
      the disease aetiology. We have screened the cholesteryl ester transfer protein
      (CETP) gene, which has been proposed as a candidate gene in AAA, by means of
      SSCP, DNA sequencing and restriction analysis in a cohort of patients with AAA
      and a matching control group drawn from the Irish population. The analysis has
      demonstrated sequence variation at four sites in the CETP gene: an A-T
      transversion in exon 9 (producing a Lys309-Stop codon substitution), a G-A
      transition in exon 14 (producing a conservative Val421-Ile substitution), a C-T
      transition in intron 12 and a G-A transition in intron 15. None of the last three
      sites corresponded with sites of functional significance in the protein,
      suggesting that this reflects neutral polymorphism at the CETP locus.
      Furthermore, the frequencies of these four polymorphisms in the AAA patient and
      control groups were not significantly different. These data therefore suggest
      that CETP may be excluded as a candidate gene in abdominal aortic aneurysm.

PMID- 9184244
TI  - The atherogenic lipoprotein phenotype is not caused by a mutation in the coding
      region of the low density lipoprotein receptor gene.
AB  - The atherogenic lipoprotein phenotype (ALP) is a common heritable trait
      characterized by a predominance of small, dense low density lipoprotein particles
      (subclass pattern B), increased levels of triglyceride-rich lipoproteins,
      reductions in high density lipoproteins, and an increased risk for myocardial
      infarction. In a previous linkage study of 11 families, evidence for tight
      linkage of subclass pattern B with the LDL receptor (LDLR) locus on chromosome
      19p13.2 was obtained. To test whether a mutation in the structural portion of the
      LDLR gene could be responsible for the phenotype, we first sequenced the exons of
      the receptor binding domain for each pair of parents in these 11 pedigrees. For
      the remaining portion of the LDLR coding region, exons as well as cloned LDLR
      cDNAs were sequenced for selected members of the pedigrees. No mutations that
      changed the amino acid sequence of the LDLR were found. We conclude that it is
      unlikely that a mutant allele of the LDLR protein is responsible for ALP.

PMID- 9184246
TI  - Submicroscopic deletion in chromosome 22q11 in trizygous triplet siblings and
      their father. Clinical variability of 22q11 deletion.
AB  - A submicroscopic deletion of chromosome 22q11 was demonstrated in three triplets
      and in their father. Two children had the typical DiGeorge sequence with at least
      three of the four cardinal features: conotruncal heart disease, hypoplastic
      thymus and typical facial features. Hypoparathyroidism was present in one of
      them. The third child had features of both DiGeorge and velo-cardio-facial
      syndrome (VCFS). The father presented with features compatible with VCFS. This
      observation further illustrates the wide variability in expression of a
      submicroscopic deletion of 22q11, even within one family.

PMID- 9184247
TI  - Reciprocal translocation 4;11 with both adjacent-1 segregants viable within a
      family.
AB  - We describe a family carrying a balanced 4;11 translocation in which both
      adjacent-1 segregants are viable. The proband had an unbalanced karyotype:
      46,XY,der(11)t(4;11)(q34.3;q23.1)mat. At 8.5 years of age he showed
      trigonocephaly, hypertelorism, epicanthal folds, down-slanting palpebral
      fissures, low-set ears, anteverted nares, down-turned carp-shaped mouth, and
      bilateral fifth finger clinodactyly. His maternal aunt was also dysmorphic with
      high-arched palate, short philtrum and mild developmental delay. Her karyotype
      was 46,XX,der(4)t(4;11)(q34.3;q23.1)pat. Other relatives who likely carried a
      chromosomally unbalanced segregant were identified from photographs and medical
      records. We compare the clinical findings in our family with descriptions of
      other similar karyotypic abnormalities from previous case reports.

PMID- 9184248
TI  - Corroboration of the lower extremity counterpart of the Poland sequence.
AB  - Gluteal and lower extremity hypoplasia with ipsilateral toe brachysyndactyly were
      noted in a 23-year-old woman similarly affected to the only previously reported
      case of the lower extremity counterpart of Poland sequence. Since no neurological
      deficit was found, and electromyographic and nerve conduction studies in the
      affected limb were normal, we propose a vascular origin which would involve the
      external iliac artery supply analogous to the subclavian artery supply disruption
      in the upper extremity Poland sequence.

PMID- 9184249
TI  - Prenatal diagnosis of mosaic tetrasomy 21q confirmed by fluorescence in situ
      hybridization.
AB  - We describe the first case of a live-born neonate with mosaic tetrasomy 21q
      confirmed by fluorescence in situ hybridization (FISH). A 38-year-old Caucasian
      female presented for amniocentesis for maternal age. Initial chromosome analysis
      of the amniocytes using GTG-banding showed a mos47,XY, +?i(12p)/46,XY karyotype.
      Follow-up studies with FISH identified the isochromosome as an i(21q); mos47,XY,
      +i(21q)/46,XY. The patient was delivered at 38+ weeks gestation and umbilical
      cord blood samples were obtained. Chromosome analysis of 43 cord blood
      lymphocytes demonstrated a 46,XY karyotype in all cells. However, peripheral
      lymphocytes taken 1 day after birth showed 1 out of 120 lymphocytes to have an
      extra chromosome determined to be an i(21q). While initial clinical exam of the
      neonate revealed similarities to Down syndrome, long-term follow up of our
      patient will be required to provide the first definitive description of the
      mosaic tetrasomy 21 syndrome.

PMID- 9184250
TI  - Two newborns with chromosome 4 imbalances: deletion 4q33-->q35 and ring
      r(4)(pterq35.2-qter).
AB  - Two patients are reported who presented with 4q deletion and r(4), respectively.
      Cytogenetic and FISH analysis defined the breakpoints respectively at bands 4q33-
      >q35 proximal to the telomere, and 4pter and 4q35.2 qter. Moreover in both cases
      rearranged chromosomes maintained telomeric sequences. The first patient showed
      some clinical features of deletion 4q and a pointed 5th finger, a characteristic
      finding in deletion 4q31-->qter. The second patient had mild dysmorphism
      associated with growth retardation.

PMID- 9184251
TI  - Ohdo syndrome: report on a Brazilian girl with additional findings.
AB  - We describe a Brazilian girl presenting Ohdo syndrome with cleft palate and
      diverticula of the bladder. Gestational history revealed the occurrence of fever
      for 12 days in the second month of gestation. To our knowledge, cleft palate and
      urinary abnormalites are hitherto undescribed features of this syndrome.
      Additional case reports could elucidate the fortuitous or causal association of
      these signs, the full phenotypic spectrum, as well as the pattern of transmission
      of the Ohdo syndrome.

PMID- 9184252
TI  - Vocal cord paralysis and cystic kidney disease in Hajdu-Cheney syndrome.
AB  - In this report we describe the clinical history and symptoms in a 36-year-old
      male with Hajdu-Cheney syndrome, an autosomal dominant condition with dissolution
      of the terminal phalanges (acro-osteolysis), characteristic craniofacial
      dysmorphism, and musculoskeletal alterations. He was admitted at that age because
      of progressive respiratory problems, with Cheyne-Stokes respiration and bilateral
      vocal cord paralysis. Terminal renal failure with cystic renal disease was
      diagnosed at the age of 14 years. The findings in the present patient illustrate
      the risk of progressive neurologic degeneration with involvement of the cranial
      nerves in patients with Hajdu-Cheney syndrome. Moreover, we confirm that cystic
      renal changes are an integral part of Hajdu-Cheney syndrome, and agree that Hajdu
      Cheney syndrome and Serpentine fibula syndrome are probably variant examples of
      the same disease.

PMID- 9184253
TI  - Prenatal detection of double aneuploidy trisomy 10/monosomy X in a liveborn twin
      with exclusively monosomy X in blood.
AB  - Both double aneuploidy and trisomy 10 are rare chromosome findings. All five
      published cases of trisomy 10 in liveborns were found to be mosaic with an
      euploid cell line. In a liveborn female twin, double aneuploidy mosaicism 47,XX,
      + 10/45,X was detected prenatally by amniocentesis performed because of severe
      intrauterine growth retardation and malformations. Chromosome analysis from
      neonatal lymphocyte cultures revealed exclusively the 45,X cell line. Double
      aneuploidy mosaicism trisomy 10/monosomy X was confirmed from skin fibroblasts.
      The child died at the age of 7 weeks. This is the first reported case of double
      aneuploidy involving trisomy 10, and the first case of trisomy 10 without a
      normal cell line in a liveborn. Prenatal diagnosis of trisomy 10 in a liveborn
      has not been published so far. The case illustrates that in specific cases
      amniotic fluid cells may reflect the karyotype of the fetus better than blood.

PMID- 9184254
TI  - Marinesco-Sjogren syndrome associated with acute myeloblastic leukemia.
AB  - Marinesco-Sjogren syndrome is a rare autosomal recessive disorder characterized
      by cerebellar atrophy, ataxia, cataracts, short stature and varying degrees of
      mental retardation. A high incidence of malignant disease associated with this
      syndrome has not so far been reported. We report the case of a 6-year-old girl
      affected with Marinesco-Sjogren syndrome, who developed acute myeloblastic
      leukemia (AML, M2), and whose karyotype was 46,XX,t(8;21),(q22;q22) in bone
      marrow blasts. This is the first report of Marinesco-Sjogren syndrome associated
      with malignant disorders.

PMID- 9184255
TI  - Complex chromosome rearrangement involving chromosomes 1, 4 and 16 revealed by
      fluorescence in situ hybridization.
AB  - A 7-year-old boy with mental retardation had apparently balanced reciprocal
      translocations, involving the telomeric regions of chromosomes 1p and 4q, which
      was detected by routine chromosome analysis. Fluorescence in situ hybridization
      (FISH) was used and also revealed the telomeric region of chromosome 16p to be
      involved in a still apparently balanced translocation-complex, impossible to
      discover with classical cytogenetic analysis. We want to emphasize the importance
      of FISH in detecting small chromosomal aberrations. We discuss whether the
      abnormal phenotype is caused by unbalanced karyotype with cryptic undetected
      translocations or small deletions or mutations in the translocation-breakpoints.

PMID- 9184256
TI  - A novel V415A mutation in exon 9 of the low density lipoprotein receptor gene
      causing familial hypercholesterolemia.

PMID- 9184257
TI  - Detection of an EcoRI restriction fragment length polymorphism in the gene
      encoding the human TBP associated factor II 30 (TAF(II)30).

PMID- 9184258
TI  - Terminal 2q deletion--a recognizable syndrome.

PMID- 9184259
TI  - Simple trapezectomy for treatment of trapeziometacarpal osteoarthritis of the
      thumb.
AB  - This is a review of 20 patients (22 operations) with symptomatic osteoarthritis
      of the first carpometacarpal joint who were treated by simple trapezectomy
      without interposition material. They were all women with a mean age of 60 years
      (46-77). The average follow-up was 2 years, ranging from 8 months to 3 years.
      Pain relief is the main contributor to the good clinical results of this
      procedure. Sixteen patients professed to be very satisfied, two had a fair result
      and four cases claimed to be unsatisfied. Range of motion (opposition and counter
      opposition) and first web space were very well preserved. Mean values of grip
      strength showed reduction of grip power on the operated side though not
      statistically. However, we did find a statistically significant difference in
      pinch strength between operated and non-operated side. In general, simple
      trapezectomy is our preferred surgical therapy in the treatment of
      carpometacarpal osteoarthritis in the elderly population.

PMID- 9184260
TI  - Macrophage-colony stimulating factor (M-CSF) is increased in the synovial-like
      membrane of the periprosthetic tissues in the aseptic loosening of total hip
      replacement (THR).
AB  - The aim of the study was to assess the eventual presence, cellular localization
      and extent of expression of the osteoclast activating cytokine M-CSF (CSF-1) in
      the periprosthetic tissues around loose total hip replacement (THR). Synovial
      like membrane was obtained from the implant-to-bone interface and pseudocapsule
      from ten total hip revisions performed for aseptic loosening and compared to ten
      hip synovial tissue samples obtained from ten patients who had primary THR for
      osteoarthritis. Avidin-biotinperoxidase complex (ABC) and alkaline phosphatase
      anti-alkaline phosphatase (APAAP) methods were used for staining and VIDAS image
      analysis for quantification. M-CSF was mainly produced by macrophages, which
      often contained wear particles, but also by some fibroblasts and vascular
      endothelial cells. The number of cells containing (per one mm2 tissue) clearly
      increased in the interface (1585 +/- 212; p < 0.01) and pseudocapsular (1456 +/-
      248; p < 0.01) tissue compared to synovial tissue (543 +/- 118). The present
      findings suggest, that inflammatory foreign-body type of response enhances
      expression of M-CSF in cases of aseptic loosening of THR. M-CSF produced in the
      synovial-like membrane in the implant-bone interface may contribute to activation
      of osteoclasts in periprosthetic bone and thus to loosening.

PMID- 9184261
TI  - Acute changes in serum calcium and parathyroid hormone circulating levels induced
      by the oral intake of five currently available calcium salts in healthy male
      volunteers.
AB  - Several calcium supplements are currently available and many of them are marketed
      without proper comparison of the bioavailability of the actual preparations. The
      aim of the present trial was to evaluate and compare the acute changes in serum
      calcium (Ca) and parathyroid hormone (PTH) levels following the oral
      administration of a vehicle and of five calcium salts currently prescribed in
      Western Europe. No significant changes in serum Ca or PTH levels were observed
      after administration of the vehicle. All calcium salts induced significant
      increases in serum Ca and decreases in serum PTH compared to baseline values.
      Comparison of the six response curves revealed a significantly greater increase
      in serum Ca and a greater decrease in serum PTH after each of the calcium salts
      than observed after the vehicle. However, no statistically significant
      differences were observed between the different calcium salts for serum Ca
      increments. The decrease in serum PTH observed after administration of an ossein
      hydroxyapatite complex was significantly less important than after the four other
      calcium salts, even if statistically different than after vehicle. When assessing
      the area under the curve (AUC) of PTH values, we observed that calcium carbonate
      and citrate induce a significantly greater decrease in serum PTH than the other
      calcium salts which are, however, statistically more active than the vehicle.
      Serum PTH is decreased under the lower limit of the normal range (10 pg/ml),
      between t60 and t120 for calcium carbonate and citrate and between t60 and t90
      for calcium gluconolactate while the mean PTH values remain within the normal
      range throughout the study with calcium pidolate, the ossein-hydroxyapatite
      complex and the vehicle. In conclusion, all calcium preparations significantly
      increase serum calcium and decrease serum parathormone, compared to what is
      observed after oral intake of a vehicle. However, significant differences in
      suppression of parathormone are observed between the different calcium
      preparations and might be of importance for their clinical use.

PMID- 9184262
TI  - Imbalance of tissue-type plasminogen activator (t-PA) and its specific inhibitor
      (PAI-1) in patients with rheumatoid arthritis associated with disease activity.
AB  - The relationship between plasma fibrinogen, D-dimer (DD), t-PA and PAI-1 and
      their correlation with disease activity (DA) were studied in 45 patients with
      rheumatoid arthritis (RA) (group B) to further understand the implication of
      fibrinolysis in the pathophysiology of RA. The control group constituted 24
      healthy subjects (group A). A Stoke index (SI) of DA was assigned to each
      patient. Patients were divided into two groups: C, minimal-mild DA (SI 1-7); D,
      moderate-severe DA (SI 8-17). Fibrinogen was elevated in RA correlating
      positively with SI and CRP. Hypercoagulability counteracted by reactive
      fibrinolysis was inferred from a 10-fold increase of DD in group B as compared to
      group A. The relatively lower levels of DD in group D compared to group C and
      their negative correlation with SI (r(s) = -0.49, p = 0.0006) indicate the
      tendency of fibrinolysis to decrease with the increase of DA. Significant
      elevation of t-PA and PAI-1 were found in group B compared to group A. While t-PA
      progressively decreased with the increase of DA (r(s) = -0.45, p = 0.0019), a
      positive relation of PAI-1 to DA was observed (r = 0.42, p = 0.0042). A 2-fold
      increase of PAI-1/t-PA molar ratio in group D compared to groups A and C as well
      as its positive correlation with SI (r(s) = 0.63, p = 0.0001) indicate the
      displacement of balance between t-PA and PAI-1 in favour of the inhibitor with
      the increase of DA in RA. The involvement of inflammatory mediators in PAI-1/t-PA
      imbalance was proposed from the relation of fibrinolytic abnormalities with the
      activity of systemic inflammatory process.

PMID- 9184263
TI  - Rheumatoid arthritis: a commonly misused diagnosis by the general population.
AB  - The purpose of this study was to explore what a young general population include
      when they answer questions concerning the diagnosis rheumatoid arthritis (RA).
      Altogether 14,420 subjects answered questionnaires concerning disease history,
      living habits and musculoskeletal pain. They were also asked specifically if
      they, or any close relative, had RA. One hundred and sixteen (1.6%) men and 115
      (1.6%) women reported that they had the disease. Altogether 14 (12%) men and 23
      (20%) women of those answering "yes" to the RA question, were found to have the
      disease verified according to their hospital records. Fifty-five (25%) of the
      subjects who reported to have RA, were classified in their hospital records as
      having other defined rheumatic diseases. Our study indicates that when the
      general population refers to the diagnosis of RA, they include most defined
      rheumatic diseases as well as unspecified arthralgia. We find it interesting that
      such a substantial number of young people report they have this serious disease.
      We therefore recommend that other measures should be used or used in addition to
      mailed questionnaires when exploring the prevalence of RA.

PMID- 9184264
TI  - Chronic calcifying tendinitis of the shoulder-therapy by percutaneous needle
      aspiration and lavage: a prospective open study of 62 shoulders.
AB  - In an open study the therapeutic value of percutaneous needle aspiration and
      lavage performed in local anaesthesia under image intensifier control in patients
      with chronic calcifying shoulder tendinitis was investigated. 60 patients (62
      shoulders) were included in the study. The average age was 48 years, and the
      median duration of shoulder pain and calcification was 24 months and 7 months
      respectively. The right shoulder was affected in 34 and the left in 24 patients;
      two patients had painful calcifications in both shoulders. In 47% X-ray showed
      calcium deposits in the contralateral shoulder. 77% of the painful deposits
      projected on the supraspinatus tendon and in most cases image intensifier
      examination showed multiple calcifications. Calcareous material could be removed
      by needle aspiration and lavage in 76% of all cases. There was no correlation
      regarding the preferred working hand and the side of calcifying tendinitis. X-ray
      controls performed after 2 months revealed a significant reduction of the size of
      calcifications. The clinical follow-up 2 and 6 months after needling showed a
      significant reduction of global pain intensity. There were also significant
      improvements in the areas of pain on movement, pain at night and impairment of
      sleep. Clinical success was independent of the radiological aspect of the
      calcifications.

PMID- 9184265
TI  - Interleukin-10 and interleukin-6 in lupus erythematosus and rheumatoid arthritis,
      correlations with acute phase proteins.
AB  - We sought to investigate the influence of interleukin-10 (IL-10) and IL-6 on the
      acute phase proteins (APP) in systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA). IL-10, IL-6, Creactive protein (CRP), alpha-1-acid glycoprotein
      (AGP), and alpha1 antichymotrypsin (ACT) serum levels were determined in one
      hundred-eight patients (71 with SLE, 37 with RA). Quantification of the serum IL
      10 level showed increased levels in SLE and RA patients as compared to healthy
      controls. Serum IL-6 level was found to be elevated in SLE and RA patients. A
      correlation between IL-10 and IL-6 serum level was found only in SLE. CRP and AGP
      serum levels were increased in RA as compared to controls, whereas in SLE only
      AGP was found elevated. A statistically significant correlation between IL-6
      serum level and CRP, AGP and ACT was found only in RA. No correlation between IL
      10 and serum level of CRP, AGP and ACT was established. Since IL-10 has a potent
      immunosuppressive activity, we expected it to be negatively correlated with APP
      levels. Surprisingly, IL-10 did not correlate with APP either in SLE or RA
      patients. However, the elevation of IL-10 serum levels in SLE and RA and the
      correlation between IL-10 and IL-6 in SLE may suggest that IL-10 may play a
      central role in inflammatory connective tissue diseases.

PMID- 9184267
TI  - The long-term results of ankle joint synovectomy for rheumatoid arthritis.
AB  - The clinical and radiological results of synovectomy for rheumatoid arthritis in
      the ankle joint were investigated in 20 ankles of 15 patients. The average follow
      up period after synovectomy was 15 years, ranging from 10 to 25 years. The
      clinical evaluation at the time of follow-up, found that only two ankles showed
      recurrence of synovitis, and no patient complained of severe ankle pain
      disturbing the activities of daily life. During the period between the
      synovectomy and our investigation, no patients required further surgical
      procedures for their ankle joints. The radiological evaluation found that in
      approximately two-thirds of the cases, deterioration of the radiological grade,
      evaluated with Larsen's criteria, had continued after synovectomy. There was no
      considerable radiological deterioration in the less-erosive subset patients,
      classified according to Ochi's criteria (1). In the unilateral synovectomized
      cases, using the non-operated ankles as the natural-course control,
      osteoarthritic changes were predominant in the operated ankle joint, and the non
      operated ankle demonstrated inflammatory disease changes. These results indicate
      that: (1) synovectomy for a rheumatoid ankle is still a preferred treatment,
      lessening the clinical symptom of persistent, marked synovial proliferation
      resistant to medical treatment. (2) Radiological deterioration continues after
      synovectomy in many cases. However, a radiogram demonstrates predominant
      osteoarthritic destruction, which indicates the natural course of rheumatoid
      destruction in the operated site could be altered by synovectomy.

PMID- 9184266
TI  - Vertebral and metacarpal morphometry as indicators of nutritional improvement.
AB  - Because of the importance of nutrition in the development of bone mass, we
      studied the nutritional state, and bone state by means of metacarpal
      radiogrammetric measurements and vertebral morphometry in a group of 40
      premenopausal women born between 1960 and 1970, mean age 29 +/- 5 years, and in
      another group of 40 postmenopausal women born between 1934 and 1944, mean age 55
      +/- 4 years. Both groups were considered normal, the main characteristic
      distinguishing them being that the women born between 1934 and 1944 grew up in a
      period of widespread malnutrition in Spain and the women born between 1960 and
      1970 grew up in a period of normal nutrition. Protein, carbohydrate and fat
      intake in these two periods differed significantly (p < 0.0001 in the three cases
      by Fischer's exact test). The values of the metacarpal measurements, anterior
      height of the dorsal vertebrae from T-4 to T-12, and posterior height from L-1 to
      L-4 between the premenopausal and postmenopausal groups of women were
      significantly different (p < 0.001) (Anova test). These findings show the
      importance of nutrition in the development of bone mass during childhood.

PMID- 9184268
TI  - Adverse drug reactions and debrisoquine/sparteine (P450IID6) polymorphism in
      patients with fibromyalgia.
AB  - OBJECTIVE: To assess the frequency of adverse drug reaction in patients with
      fibromyalgia in relation to medications prescribed for this condition. To
      evaluate the potential role of the P450IID6 phenotype in the pathogenesis of
      these adverse drug reactions. METHODS: Thirty-five patients with fibromyalgia
      were assessed using a structured questionnaire with demographic and clinical data
      and perceived adverse drug reactions. A sample of 60 patients with rheumatoid
      arthritis and 62 patients with localized back pain served as controls. The
      P450IID6 phenotype was determined for each of the fibromyalgia patients. RESULTS:
      Overall, 141 patients had used NSAID and 79 (56%) of them reported adverse
      effects. Antidepressant drugs were used by 68 patients and 35 (51%) patients had
      adverse effects. Muscle relaxant drugs were used by 48 patients and 15 (31%) of
      them reported side effects. Analgesics were used by 122 patients and 22 (18%) had
      experienced adverse effects. Statistical differences in the frequency of adverse
      effects were found with antidepressant drugs in the fibromyalgia group, compared
      with rheumatoid arthritis (p=0.01) and back pain (p=0.02). Four of the 35
      patients (11.4%) had a metabolic ratio (M.R.) greater than 0.30 (log M.R.= -0.52)
      indicative of the poor metabolizers (PM) phenotype. M.R. varied from 0.005 (log
      M.R. = -2.30) to 4.99 (log M.R. = 0.70). CONCLUSIONS: The problem of adverse drug
      reactions in fibromyalgia patients does not appear to correlate with the PM
      phenotype of the P450IID6 oxidative enzyme. It also is unlikely that altered
      xenobiotic detoxification attributable to this PM phenotype would have a
      significant role in the development of fibromyalgia.

PMID- 9184270
TI  - Systemic lupus erythmatosus associated with autoimmune hepatitis two cases with
      novel autoantibodies to transfer RNA-related antigens.
AB  - Two cases of systemic lupus erythematosus (SLE) with autoimmune hepatitis are
      reported. Both patients had a mild form of SLE without central nervous system or
      renal involvement and showed a rapid response to corticosteroid therapy. Neither
      of them had antibodies to mitochondria, smooth muscle, and liver/kidney microsome
      1 related to autoimmune hepatitis. Instead, novel autoantibodies which react with
      transfer RNA-related antigen were detected. These autoantibodies could be a
      useful marker for classification of SLE associated with autoimmune hepatitis.

PMID- 9184269
TI  - Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and
      psoriatic arthritis: report of five cases and review of the literature.
AB  - Pneumonitis is emerging as one of the most unpredictable and potentially serious,
      adverse effects of treatment with MTX. Its prevalence in rheumatoid arthritis
      (RA) has been estimated from several retrospective and prospective studies to
      range from 0.3% to 18%. On the other hand, MTX-induced pneumonitis seems to be
      very rare in psoriatic arthritis (PsA). Our review of 194 RA patients and 38 PsA
      patients receiving MTX has identified four RA patients and one PsA patient with
      MTX-induced pneumonitis, giving a prevalence of 2.1% and 0.03%, respectively.
      Diagnosis was suggested by clinical history and radiographic findings, but the
      bronchoalveolar lavage plays an important role both in excluding infectious
      agents and in providing information for understanding the pathogenesis of lung
      injury. The presence of a lymphocyte alveolitis with a predominance of CD4+ T
      cells in 3 RA patients and CD8+ T cells with a concomitant increase in
      neutrophils in another case suggests that immunologically mediated reactions may
      be one damage mechanism in MTX-induced pneumonitis. Although risk factors for MTX
      induced pulmonary toxicity are poorly understood, the presence in 3 out of 5 of
      our patients of pre-existing lung disease, represented by diffuse interstitial
      changes on chest X-ray, and mild bronchial asthma in two RA patients and by
      pulmonary silicosis in the patient with PsA may account for a predisposition to
      the development of MTX pneumonitis.

PMID- 9184271
TI  - Arthritis as the presenting symptom of diverticulitis.
AB  - We describe a patient in whom peripheral arthritis was the presenting symptom of
      diverticulitis. The joint inflammation resolved only after treatment for the
      gastrointestinal disease. The pathogenesis, clinical aspects and management of
      this condition are discussed.

PMID- 9184272
TI  - Pyogenic arthritis caused by streptococcus equisimilis (group-C streptococcus) in
      a patient with AIDS.
AB  - A patient with the Acquired ImmunoDeficiency Syndrome (AIDS) treated with a daily
      low dose of corticosteroids for chronic atopic dermatitis experienced a sudden
      episode of unilateral knee arthritis. Culture of the purulent synovial liquid
      yielded a pure culture of Streptococcus Equisimilis. A four week period of
      intravenous antibiotherapy combined with repeated drainages allowed a complete
      recovery of articular function.

PMID- 9184273
TI  - Psoriatic arthritis and minocycline induced autoantibodies.
AB  - A case of psoriatic arthritis where diagnosis was originally complicated by the
      presence of minocycline-induced auto-antibodies and hepatic dysfunction. The
      range of auto-antibodies associated with minocycline includes ds DNA and SCL 70.

PMID- 9184274
TI  - Salmonella osteomyelitis in a patient with human immunodeficiency virus
      infection.

PMID- 9184275
TI  - Diastolic impairment in asymptomatic systemic lupus erythematosus patients.

PMID- 9184276
TI  - Clinical characteristics related to methotrexate-induced pancytopenia.

PMID- 9184278
TI  - Creatine kinase release after catheter-based coronary intervention.

PMID- 9184277
TI  - von Willebrand factor antigen and adhesive molecules in Wegener's granulomatosis
      and microscopic polyangiitis.

PMID- 9184279
TI  - Who is an interventional cardiologist?

PMID- 9184280
TI  - Brachial, radial, or femoral approach for elective Palmaz-Schatz stent
      implantation: a randomized comparison.
AB  - From October 1994 to November 1995, 150 male eligible patients were randomly
      assigned to Palmaz-Schatz stent implantation through 6 French catheters using the
      femoral (puncture) (n = 56), radial (puncture) (n = 56), or brachial (cutdown) (n
      = 38) approach at 6 participating Belgian centers. Acenocoumarol was given for 1
      month after stenting. END POINTS: Primary-entry site complications (bleeding,
      haematoma, transfusion, occlusion, surgery) poststent implantation. Secondary
      success rate, stent thrombosis, Q or non Q wave MI, repeat PTCA, CABG, CVA,
      haemorrage, death. There were no statistically significant differences between
      the three groups for base line and angiographic patient characteristics,
      procedural characteristics, in hospital outcome, average hospitalisation time
      after stenting, events during the month after stenting, or local complications at
      1 month follow-up. The only statistically significant difference was the arterial
      time of the procedure: mean +/- SD (minutes) brachial 31.0 +/- 10.02 *P < 0.001,
      femoral 42.2 +/- 21.8, radial 55.8 +/- 31.3 **P < 0.0001 (*brachial vs. femoral,
      **brachial vs. radial). There was a clear trend toward more technical
      difficulties and more problems with the radial approach. In each group: vascular
      surgery at entry site: 0%, blood transfusion: 0%. In our study, local
      complications and length of hospital stay were similar with the three possible
      approaches, and brachial approach was associated with a shorter arterial time.

PMID- 9184281
TI  - Ulnar and radial coronary interventions: distal reaches of arterial access.

PMID- 9184282
TI  - Evaluation of the cathetron system for recycling angioplasty catheters.
AB  - The Cathetron (Minntech Corporation, Minneapolis, MN) peracetic acid-based
      reprocessing method for percutaneous transluminal coronary angioplasty (PTCA)
      catheters was evaluated for ability to sterilize and maintain catheter integrity.
      The balloons and lumens of 42 catheters (140 reprocessing cycles) were inoculated
      with suspensions of Staphylococcus epidermidis, S. aureus, Pseudomonas
      aeruginosa, and Bacillus circulans. Five catheters failed the initial evaluation
      of mechanical integrity and were discarded. Cultures from 37 catheter lumens,
      balloons, and hubs (n = 349) were negative following reprocessing. The Cathetron
      system reliably sterilized PTCA catheter, however, further studies using
      different brands of catheters and evaluating catheter sterility over time under
      storage conditions are required.

PMID- 9184283
TI  - A disposable society: is it time for a change?

PMID- 9184284
TI  - Palmaz stent compression in patients following carotid artery stenting.
AB  - Carotid artery stenting is being investigated as a therapeutic strategy for the
      management of bifurcation stenosis. Palmaz stents were deployed successfully in
      the carotid arteries of 112 patients using high-pressure balloon inflations. In
      11 out of 70 patients who came for 6-mo follow-up angiography, a stent collapse
      was noted. Carotid ultrasound was able to detect stent collapse in only two
      patients at follow-up. Only one patient who had collapse of stent along its
      entire length was symptomatic at follow-up. Repeat balloon angioplasty was
      performed in 5 patients, 3 of whom had a Wallstents deployed within the Palmaz
      stent. CONCLUSION: Stent collapse was observed in a significant number of Palmaz
      stents within 6 mo of placement in the carotid arteries. These observations
      should influence the choice of stents for the treatment of extracranial carotid
      disease.

PMID- 9184285
TI  - Progression of atherosclerosis after venous coronary artery bypass graft surgery:
      a 15-year follow-up study.
AB  - We investigated the influence of progression of atherosclerosis on clinical
      outcome in a cohort of 428 consecutive patients with isolated venous coronary
      artery bypass graft surgery followed prospectively for 15 years. In 189 patients
      307 repeat coronary angiograms were performed because of recurrent signs of
      ischemia. Progression in the native coronary circulation only was found in 38
      angiograms (12%), in both the native circulation and in venous grafts in 66
      angiograms (21%), in venous grafts only in 135 angiograms (44%), and no
      progression was found in 68 angiograms (22%). In all the angiographies with a
      proven progression in the native coronary arteries, 40% was found to be distal to
      a vein graft insertion. In multivariate analysis the number of distal anastomoses
      predicts progression in both the native circulation and in venous grafts. Thus,
      progression is determined by the extensiveness of coronary artery disease at
      operation. Also, the interval between operation and repeat angiography predicts
      progression in the native circulation. We conclude that clinical outcome is also
      determined by progression in the native coronary circulation. Secondary
      prevention may, therefore, benefit not only the long-term result in patients with
      venous bypass grafts but probably also in patients with any type of coronary
      bypass surgery.

PMID- 9184286
TI  - Long-term evaluation of vein bypass grafts: lessons to be learned.

PMID- 9184287
TI  - Coronary blood flow velocities during rotational atherectomy.
AB  - This study was designed to evaluate the alterations in doppler derived coronary
      blood flow velocities and flow reserve following rotational ablation. Changes in
      doppler derived coronary blood flow velocity variables have been valuable in
      assessing the physiological outcome following coronary balloon angioplasty.
      Rotational ablation's mechanism of plaque removal could alter distal vascular bed
      characteristics, and, as a result, intracoronary blood flow velocities and the
      coronary flow reserve. A 12-MHz doppler guidewire recorded intracoronary phasic
      velocities and coronary flow reserve (as assessed by the hyperemic response to
      adenosine [12-18 mcg intracoronary]) in 28 patients, before and after rotational
      ablation of 30 lesions. Adjunctive balloon angioplasty was performed in 27 of 28
      patients (96%). Rotational ablation and adjunctive balloon angioplasty
      successfully reduced the lesion diameter (87 +/- 9% to 14 +/- 11%; P < 0.001). A
      significant increase in the mean distal average peak velocity (25 +/- 13 cm/sec,
      before; 47 +/- 22 cm/sec, after; P < 0.001), and decrease in the proximal to
      distal average peak velocity ratio, (2.1 +/- 1.3; to 1.2 +/- 0.4; P = 0.002) was
      recorded. The mean distal diastolic to systolic velocity ratio (before, 1.4 +/-
      0.7; after, 1.6 +/- 0.8; P = 0.44) and the coronary flow reserve (before, 1.6 +/-
      0.6; after, 1.5 +/- 0.5; P = 0.34) did not increase despite increases in distal
      velocities, following successful intervention. Doppler derived distal coronary
      blood flow velocities increased following rotational ablation and adjunctive
      balloon angioplasty, with resolution of transstenotic velocity gradient. Changes
      in distal phasic velocity pattern and coronary flow reserve, immediately after
      the intervention, were not useful in the assessment of the functional outcome and
      may be related to abnormalities in distal vascular bed vasoreactivity produced by
      rotational ablation.

PMID- 9184288
TI  - Comparative effects of dobutamine and amrinone on coronary blood flow in patients
      with idiopathic dilated cardiomyopathy.
AB  - Although amrinone has favorable hemodynamic effects in patients with congestive
      heart failure, little is known about its effects on coronary blood flow (CBF). We
      compared the effects of intravenous low-dose dobutamine and amrinone on CBF in 10
      patients with dilated cardiomyopathy using a Doppler guidewire. We infused
      dobutamine at a dose of 5 and 10 microg/kg/min for 5 min. After the end of each
      stage, coronary flow velocity (CFV) and coronary arterial diameter (CAD) in the
      proximal left anterior descending coronary artery, and hemodynamic variables were
      obtained. After the CFV and hemodynamics returned to baseline, we infused 1 mg/kg
      of amrinone over 5 min, and obtained these variables at 5 and 10 min after the
      cessation of the infusion. CAD did not increase with dobutamine, but
      significantly increased after amrinone (% increase: 10 +/- 7%; P < 0.001 vs.
      baseline). CFV progressively increased with dobutamine (5 microg/kg/min: 21 +/-
      26%; P < 0.05 vs. baseline; 10 microg/kg/min: 53 +/- 42%; P < 0.005 vs. baseline
      and 5 microg/kg/min), but slightly decreased after amrinone (-4 +/- 17%; P = not
      significant vs. baseline). CBF increased during dobutamine (5 microg/kg/min: 25
      +/- 29%; P < 0.05; 10 microg/kg/min: 66 +/- 55%; P < 0.005) and after amrinone
      (19 +/- 22%; P < 0.05) compared to that at baseline. Although there was a
      significant correlation between the percent increase in CFV and that in dP/dt
      during dobutamine infusion (r = 0.82, P < 0.001), this correlation was not
      observed after amrinone (r = 0.23). In conclusion, although both agents
      significantly increased CBF in patients with dilated cardiomyopathy, they do so
      by different mechanisms. Amrinone mainly increases CBF by causing dilatation of
      epicardial coronary arteries. These results suggest that amrinone has beneficial
      effects on coronary flow dynamics in dilated cardiomyopathy.

PMID- 9184289
TI  - Coronary blood flow in patients with idiopathic dilated cardiomyopathy.

PMID- 9184290
TI  - Acute occlusion of a left internal mammary artery graft immediately after redo
      coronary artery bypass surgery: successful rescue PTCA.
AB  - A patient with a patent left internal mammary artery (LIMA) to the left anterior
      descending (LAD) artery required repeat bypass grafting to the distal right
      coronary artery (RCA). Intraoperative injury to the LIMA resulted in acute
      anterior myocardial infarction, which was managed by successful rescue
      percutaneous transluminal coronary angioplasty (PTCA).

PMID- 9184291
TI  - Prolonged catheter-induced coronary artery spasm mimicking fixed stenosis.
AB  - Two cases of prolonged catheter-induced right coronary artery spasm, mimicking
      fixed stenoses, are presented. In one case, the spasm appeared at the same place
      in sequential catheterizations. This angiographic finding may be easily
      misinterpreted as a fixed lesion, leading to unnecessary attempts at angioplasty.

PMID- 9184292
TI  - Angioplasty and stenting of an unprotected left main bifurcation lesion.
AB  - A case of unprotected bifurcation left main disease treated on 2 occasions by
      angioplasty and stenting is presented. This case demonstrates the 2 main features
      of salvage angioplasty, namely medically refractory rest angina and refused
      bypass surgery. In addition, it presents short inflation time angioplasty for
      sole or main conduits and treating the left main as a bifurcation lesion.

PMID- 9184293
TI  - Management of resistant coronary lesions by the cutting balloon catheter: initial
      experience.
AB  - Resistant coronary lesions remain a challenge for modern angioplasty. Classical
      approaches include high-pressure inflations, prolonged inflations, or balloon
      oversizing. More recently, new technologies like rotablator, atherectomy, or
      laser have been proposed as adjunct to balloon angioplasty for the treatment of
      these specific lesions. However, all these technologies remain more difficult to
      handle, costly, and they do not offer long-term benefit over conventional
      methods. Therefore, a simple device such as the cutting balloon catheter which
      has been developed from a standard over the wire balloon catheter, may prove to
      be useful in resistant coronary lesions. We present our single center experience
      using the new cutting balloon catheter in six resistant lesions.

PMID- 9184294
TI  - Treatment of coronary artery disease in an anomalous coronary artery by placement
      of an intracoronary stent.
AB  - We report the use of coronary stenting to treat disease in an anomalous coronary
      artery. The patient had a single coronary artery with anomalous left anterior
      descending artery arising from the right sinus of Valsalva and coursing between
      the aorta and pulmonary artery. Although balloon angioplasty has been used in
      patients with anomalous coronary arteries, this is the first report of stent
      placement in this circumstance.

PMID- 9184295
TI  - Placement of peripherally inserted central catheters in the cardiac
      catheterization laboratory.
AB  - This report describes our experiences with three patients requiring several weeks
      of central venous access for various intravenous therapies. These particular
      patients posed a considerable challenge for bedside placement of a peripherally
      inserted central catheter, so the catheters were placed in the cardiac
      catheterization laboratory by the cardiology team involved using a different
      technique for each patient.

PMID- 9184296
TI  - Trouser-like stenting: a new technique for bifurcation lesions.
AB  - We report on a new technique of stenting a bifurcation lesion. A manually bent
      180 degrees hinged slotted tube stent was implanted using the kissing balloon
      technique (resembling two trouser legs). In addition, the proximal part of the
      main vessel was covered with a stent mounted on two balloons corresponding to the
      trousers' waist. This "trousers-like stent technique" ensures open accesses to
      both vessels not obstructed by stent struts and could be a promising solution for
      main bifurcation lesions.

PMID- 9184297
TI  - Evaluation of a pressure-recording guidewire in patients with coronary arterial
      disease.
AB  - The accuracy and feasibility of coronary arterial pressure measurements with a
      0.018-in. pressure-recording guidewire (PRGW) was evaluated in patients.
      Transstenotic pressure gradients were measured with the PRGW and a guiding
      catheter, at baseline and during coronary vasodilatation. Proximal intracoronary
      pressure was measured with both systems before and after gradient measurements.
      Zero pressure was measured with the PRGW before and after intracoronary use. The
      average of all proximal intracoronary PRGW readings were close to guiding
      catheter values, but there were substantial individual deviations. Average change
      in proximal deviation before and after gradient measurements was -1 mm Hg,
      standard deviation (S.D.) 7.6, range -16 to 15. Errors in zero pressure
      measurements after intracoronary use (average 2.8 mm Hg, S.D. 8.8, range -9 to
      35) were much greater than before use (average 0.1 mm Hg, S.D. 1.4, range -4 to
      3, P < 0.001). The PRGW was successfully introduced through an 8F guiding
      catheter and positioned across the stenosis in 21 of 26 attempts (81%).
      Intracoronary advancement of the PRGW through a double-lumen multifunctional
      probing catheter was successful in all nine attempts. In conclusion, errors in
      PRGW-measurements caused uncertainty in gradient interpretation. However, we
      found the wire useful in several cases, particularly for exclusion of
      hemodynamically significant lesions. The steerability of the wire is inferior to
      ordinary guidewires, but it can be advanced to a distal intracoronary position
      through an over-the-wire catheter.

PMID- 9184298
TI  - Characterization of intra-arterial flow velocity within left coronary to
      pulmonary artery fistula.
AB  - The physiology of a coronary to pulmonary artery fistula has not been well
      characterized. This case report demonstrates the flow velocity pattern of a
      coronary fistula to the pulmonary artery which supports the hypothesized
      physiology that flow is predominantly continuous without a phasic pattern. The
      flow velocity within a coronary fistula has not been previously demonstrated.

PMID- 9184299
TI  - Coronary AVE micro stents: serial quantitative angiography and histology in a
      canine model.
AB  - The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3
      mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5
      to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and
      chronic implantation were obtained in 52 stented coronary segments of 18 dogs.
      Three hearts with 8 stented coronary segments were harvested after 24 hr, 3
      hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15
      stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments
      were harvested at 24 weeks post-deployment. There were no procedural
      complications, deaths, or acute vessel closures. The average lumen diameter of
      the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average
      diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P <
      0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent
      of stenosis was <30% in all animals. Histologically, a peak of inflammation was
      visible at 2 weeks; however, the extent of luminal narrowing reached its peak at
      8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of
      intimal thickening remained relatively constant throughout the different time
      points (<200 microm). Overall, these data suggest that constrictive remodeling
      within the stented segment occurs at 8 weeks in this animal model. The later
      increase of the stented segment dimensions as well as higher net gain at 24 weeks
      compared to 8 weeks after deployment suggests that this constriction is a
      transitory phenomenon.

PMID- 9184300
TI  - Coronary AVE micro stents: do we need another stent?

PMID- 9184301
TI  - Balloon valvuloplasty: confusing assessment.

PMID- 9184302
TI  - If youth but knew, if age but could...

PMID- 9184303
TI  - Emergent mitral percutaneous valvuloplasty before emergent liver transplantation.

PMID- 9184304
TI  - Genomic survey of bipolar illness in the NIMH genetics initiative pedigrees: a
      preliminary report.
AB  - Four sites collaborated with the NIMH to develop a resource for the genetic study
      of bipolar (BP) illness. Common methods of ascertainment and assessment were
      developed in 1989. A series of families with a bipolar I (BPI) proband and at
      least one BPI or schizoaffective, bipolar type (SA/BP) first-degree relative has
      been studied. We now report initial data from a genomic survey with an average
      intermarker interval of 10 cM on 540 subjects from 97 families. This is the
      largest commonly ascertained and assessed linkage sample for bipolar illness
      reported to date; it includes 232 subjects with BPI, 32 SA/BP, 72 bipolar II
      (BPII), and 88 unipolar, recurrent (UPR). Nonparametric methods of analysis were
      employed, with all sites using affected sib pair analysis. The strongest findings
      thus far appear to be on chromosomes 1, 6, 7, 10, 16, and 22. Support has also
      been found for some previously reported linkages, including 21q and possibly
      Xq26. All these areas (as well as others) will be followed up with additional
      markers and further analyses. No locus tested thus far meets stringent criteria
      for an initial finding of significant linkage.

PMID- 9184305
TI  - Initial genomic scan of the NIMH genetics initiative bipolar pedigrees:
      chromosomes 3, 5, 15, 16, 17, and 22.
AB  - As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we
      carried out a genomic scan of chromosomes 3, 5, 15, 16,17, and 22. Genotyping was
      performed on a set of 540 DNAs from 97 families, enriched for affected relative
      pairs and parents where available. We report here the results of the initial 74
      markers that have been typed on this set of DNAs. The average distance between
      markers (theta) was 12.3 cM. Nonparametric analysis of excess allele sharing
      among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to
      test three hierarchical models of affected status. D16S2619 gave some evidence of
      linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1,
      bipolar 2 and schizoaffective-bipolar type individuals are considered affected).
      Nearby markers also showed increased allele sharing. A second interesting region
      was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed
      increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of
      affected status become more broad. MOD score analysis also supported the possible
      presence of a susceptibility locus in this region of chromosome 5. A pair of
      adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased
      allele sharing in the broad model. Several isolated markers had excess allele
      sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of
      2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around
      D22S533 as the most interesting. Thus, several regions showed modest evidence for
      linkage to bipolar disorder in this initial genomic scan of these chromosomes,
      including broad regions near previous reports of possible linkage.

PMID- 9184306
TI  - Initial genome scan of the NIMH genetics initiative bipolar pedigrees:
      chromosomes 1, 6, 8, 10, and 12.
AB  - A report on an initial genome screen on 540 individuals in 97 families was
      collected as part of the NIMH Genetics Initiative on Bipolar Disorder. Families
      were ascertained to be informative for genetic linkage and underwent a common
      ascertainment and assessment protocol at four clinical sites. The sample was
      genotyped for 65 highly polymorphic markers from chromosomes 1, 6, 8, 10, and 12.
      The average intermarker interval was 16 cM. Genotypic data was analyzed using
      affected sib pair, multipoint affected sib pair, and pedigree analysis methods.
      Multipoint methods gave lod scores of approximately two on chromosomes 1, 6, and
      10. The peak lod score on chromosome 6 occurred at the end of the q-arm, at some
      distance from the 6p24-22 area previously implicated for schizophrenia. We are
      currently genotyping additional markers to reduce the intermarker interval around
      the signals. The interpretation of results from a genome screen of a complex
      disorder and the problem of achieving a balance between detecting false positive
      results and the ability to detect genes of modest effect are discussed.

PMID- 9184308
TI  - Initial genome screen for bipolar disorder in the NIMH genetics initiative
      pedigrees: chromosomes 2, 11, 13, 14, and X.
AB  - We report on an initial genome screen of 540 individuals from 97 families
      collected as part of the NIMH Genetics Initiative Bipolar Group. Among the
      individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88
      with major depressive disorder-recurrent type (UPR), and 32 with schizoaffective
      disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13,
      14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University.
      Tests for linkage were performed using nonparametric affected sib-pair and whole
      pedigree methods with three definitions of affected status. Three regions of
      interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and
      14, a disease locus with relative risk lambda(i) = 1.5 could be excluded in <10%
      of the genetic distance studied, while a locus conferring lambda(i) = 3 or
      greater could be excluded across at least 96%. The autosomal region that could
      not be excluded even with lambda(i) = 5 was near 13q14-32. In this region, two
      point affected sib-pair analyses revealed a pair of consecutive loci with excess
      sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X
      chromosome, nonparametric multipoint affected sib-pair analyses revealed peak
      total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the
      markers in Xp22 would have lambda(i) = 3.6 in affected brother-brother pairs,
      while a locus linked to the markers in Xq26-28 would have lambda(i) > 1.9 in
      affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest
      areas of interest for further studies.

PMID- 9184307
TI  - Initial genome scan of the NIMH genetics initiative bipolar pedigrees:
      chromosomes 4, 7, 9, 18, 19, 20, and 21q.
AB  - An initial genome scan was performed on 540 individuals from 97 families
      segregating bipolar disorder, collected through the National Institutes of Mental
      Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126
      marker loci (approximately 68,000 genotypes) mapping to chromosomes 4, 7, 9, 18,
      19, 20, and 21q, under three affection status models. Modest increases in
      identical-by-descent (IBD) allele sharing were found at the following loci:
      D4S2397 and D4S391 (P < 0.05) on 4p, D4S1647 (P < 0.05) on 4q, D7S1802 and
      D7S1869 (low P = 0.01) on 7p, D9S302 (P = 0.004) on 9q, and D20S604 on 20p and
      D20S173 on 20q (P < 0.05). In addition, five markers on 7q displayed increased
      IBD sharing (P = 0.046-0.002). Additional ASP analyses on chromosomes 18 and 21q
      marker data were performed using disease phenotype models defined previously. On
      chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in
      allele sharing (P = 0.02), implying that the reported linkages in these regions
      were not confirmed. On chromosome 21q, a cluster of markers within an
      approximately 9 cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited
      excess allele sharing (P = 0.041-0.008). Multilocus data on overlapping marker
      quartets, from D21S1265 to D21S1255, which were consistent with increased IBD
      sharing (P < 0.01, with a low of 0.0009), overlapped a broad interval of excess
      allele sharing reported previously, increasing support for a susceptibility locus
      for bipolar disorder on 21q.

PMID- 9184309
TI  - The sword of Damocles: the psychosocial impact of familial spinocerebellar ataxia
      in South Africa.
AB  - A survey was conducted on 30 unaffected individuals from a family with autosomal
      dominant late onset spinocerebellar ataxia in South Africa. The psychological
      impact of the disorder on individual lives, risk awareness, attitudes towards
      affected kin and reproduction were evaluated. Respondents employed various
      psychological strategies to deal with the threat of developing the disorder. In a
      comparison of "assigned" risk with "perceived" risk, 80% of unaffected persons
      reported incorrect perceptions of personal risk status. The disorder had little
      impact on attitudes concerning reproduction; the majority of individuals at risk
      wanted more children. These issues need to be addressed in the genetic and
      predictive testing service for familial ataxia in South Africa.

PMID- 9184310
TI  - Anticipation in schizophrenia: biology or bias?
AB  - Anticipation is a genetic phenomenon wherein age of disease onset decreases and/
      or severity increases in successive generations. Anticipation has been
      demonstrated for several neuropsychiatric disorders with expanding trinucleotide
      repeats recently identified as the underlying molecular mechanism. We report here
      the results of an analysis of anticipation performed with multiplex families
      segregating schizophrenia. Thirty-three families were identified through the NIMH
      Genetics Initiative that met the following criteria: had at least two affected
      members in successive generations and were not bilineal. Affectation diagnoses
      included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS.
      Additional analyses included the Cluster A personality disorders. Three indices
      of age of onset were used. Disease severity was measured by several different
      indices. Four sampling schemes as suggested by McInnis et al. were tested, as
      well as additional analysis using pairs ascertained through the parental
      generation. Anticipation was demonstrated for age of onset, regardless of the
      index or sampling scheme used (P<0.05). Anticipation was not supported for
      disease severity. Analyses that took into account drug use and diminished
      fecundity did not affect the results. While the data strongly support
      intergenerational differences in disease onset consistent with anticipation, they
      must be viewed cautiously given unavoidable biases attending these analyses.

PMID- 9184311
TI  - No association between polymorphisms in the human dopamine D3 and D4 receptors
      genes and alcoholism.
AB  - The human dopamine D2 receptor gene (DRD2) has received considerable attention
      for the past several years as a potential candidate that may affect
      susceptibility to alcoholism. The association studies that compared the
      frequencies of alleles of DRD2 gene between alcoholics and control groups have
      produced equivocal results. Dopamine D3 and D4 receptor genes (DRD3 and DRD4) are
      in the same class as DRD2 but with different pharmacological properties. We have
      used relative risk and haplotype relative risk approaches to test associations
      between alleles of DRD3 and DRD4 genes and alcoholism. For relative risk studies
      162 probands from multiple incidence alcoholic families have been compared to 89
      psychiatrically normal controls. Haplotype relative risk approaches have used 29
      alcoholic probands in which both parents were available for genotyping. The Bal I
      restriction enzyme site in DRD3 and tandem repeat (VNTR) in DRD4 genes
      polymorphisms were used to genotype the above samples. The results of relative
      risk approaches for both DRD3 and DRD4 genes were negative for comparisons of
      alcoholics and subtypes of alcoholics with normal controls. Haplotype relative
      risk approaches also were negative for both genes. These results suggest that any
      role played by these receptors may account for only part of the variation in
      susceptibility to alcoholism.

PMID- 9184312
TI  - Selection of homogeneous populations for genetic study: the Portugal genetics of
      psychosis project.
AB  - Molecular genetic studies of psychiatric disorders must face the possibility that
      despite the significant contribution of genetic factors to the expression of
      syndromes like schizophrenia, these syndromes may be a heterogeneous collection
      of genetic and non-genetic illnesses. These illnesses may be etiologically
      distinct from each other and still share many clinical features in common.
      Linkage studies of families with multiple affected members tend to favor the
      selection of genetic forms of a syndrome but can still represent a heterogeneous
      set of different genetic illnesses. To limit the potential genetic heterogeneity
      of a study sample, we selected a population that was geographically isolated and
      was historically relatively genetically homogeneous. We then assessed the
      relative level of homogeneity utilizing a surname analysis of the population of
      the Azores, mainland Portugal, rural USA, and urban USA. The average number of
      families with the same last name corrected for population size in the Azores is
      30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population
      and 0.38 in an urban American population. The results of this analysis indicate
      that the Azores have the highest degree of homogeneity, and mainland Portugal has
      a high degree of homogeneity.

PMID- 9184313
TI  - Cladistic analysis of disease association with tyrosine hydroxylase: application
      to manic-depressive disease and alcoholism.
AB  - We evaluated the involvement of tyrosine hydroxylase (TH) mutations in
      susceptibility to manic-depressive disease (MDD) and alcoholism (ALC) with a
      cladistics-based association analysis. Eighty-one probands with MDD, 113 probands
      with alcoholism, and 80 normal controls were tested for differences in frequency
      of nine haplotypes at the TH locus. The haplotypes were comprised of four
      restriction fragment length polymorphisms spanning the TH gene. A cladogram
      constructed from the haplotypes provided the evolutionary context for a nested
      statistical analysis. Statistically significant evidence was found for
      association of a subgroup of the sample for each of the disorders with different
      branches of the gene tree, but the findings were sensitive to minor changes in
      estimated haplotype frequencies.

PMID- 9184314
TI  - Selecting a control group in studies of the familial coaggregation of two
      disorders: a quantitative genetics perspective.
AB  - We sought to compare four different definitions of control groups in studies of
      the coaggregation between two disorders (A and B) on: 1) their ability to detect
      valid familial coaggregation; 2) their liability to artifactual evidence for
      familial coaggregation; and 3) their robustness to the overselection of comorbid
      cases. Using a quantitative genetic model of transmission, we simulated sibling
      pairs with familial and nonfamilial sources of comorbidity. Four different
      definitions of controls were tested to predict disorder B in siblings of cases
      vs. controls: 1) unscreened controls included subjects with A or B as well as
      subjects with either A or B; 2) in the symmetrical selection method, controls
      included only subjects without A; 3) supernormal controls included only subjects
      without A or B; and 4) in the pure proband method, cases included subjects with A
      only, and controls included only subjects without A or B. In the absence of
      selection bias, 1) the unscreened control and the symmetrical selection methods
      did not yield spurious evidence for familial coaggregation and could detect
      familial coaggregation; 2) the supernormal controls yielded spurious evidence of
      familial coaggregation; and 3) the pure proband method sometimes yielded spurious
      evidence for negative familial coaggregation, and had limited power to detect
      familial coaggregation. However, the pure proband method was the only one
      unaffected by overselection of comorbid cases. In the absence of selection bias,
      both the unscreened control and the symmetrical selection methods are
      appropriate, and the robustness of the pure proband method to overselection of
      comorbid cases may be an interesting feature in studies using clinical samples.
      Moreover, quantitative genetics methods may offer important advantages in the
      study of familial coaggregation.

PMID- 9184315
TI  - Exclusion of linkage between bipolar affective disorder and chromosome 16 in 12
      Australian pedigrees.
AB  - Several recent reports of possible susceptibility loci for bipolar affective
      disorder (BAD) have identified sites on a number of chromosomes. Specifically,
      two Danish studies have suggested the presence of a susceptibility locus for BAD
      on chromosome 16p13. As the first step of a whole genome scan, we screened 12
      Australian families with markers at 16p13 and also a number of markers spanning
      the entirety of chromosome 16. Linkage analysis was undertaken using both the
      parametric lod score method (two- and multipoint) with different models and
      diagnostic thresholds, and the nonparametric affected pedigree member (APM)
      method. Results of lod score analysis convincingly excluded the 16p13 region from
      linkage to BAD in these families, while APM provided no support for linkage.
      Furthermore, using the broad definition of BAD, with individuals affected by
      bipolar I and II and recurrent unipolar disorders included, the entire chromosome
      was excluded from linkage to BAD with autosomal-dominant transmission at a
      maximum age-specific penetrance of 60%, and with autosomal-dominant and recessive
      modes of transmission at a maximum age-specific penetrance level of 90%.
      Diagnostic thresholds which did not include unipolar affected individuals were
      somewhat less informative. However, a majority (between 63-96%, depending upon
      the model) of the chromosome was clearly excluded using narrow diagnostic
      thresholds. Moreover, no positive lod scores were obtained at theta = 0.00 for
      any tested model or diagnostic threshold. Our results indicate that no linkage
      exists between BAD and chromosome 16 markers in this group of Australian
      families.

PMID- 9184316
TI  - 6p24-22 region and major psychoses in the Eastern Quebec population. Le Groupe
      IREP.
AB  - Recent reports of a linkage trend in 6p24-22 for schizophrenia (SZ), in different
      samples, were tempered by the concurrent evidence of negative reports in other
      samples. In the studies showing positive results, different definitions of
      affection and a wide spectrum of diagnoses were used. Our objectives were not
      only to test for linkage at 6p24-22 in the Eastern Quebec population, but also to
      test whether this putative vulnerability locus was either selectively linked to
      schizophrenia (SZ), or to bipolar disorder (BP), or to both major psychoses.
      Parametric and nonparametric linkage analyses with 12 microsatellite markers in
      6p24-p22 were performed on a sample of 18 large multigenerational pedigrees (N =
      354) either affected by SZ, or by BP, or equally affected by both major psychoses
      (i.e., mixed pedigrees). Three affection definitions were usually tested in our
      program: one on schizophrenia (SZ), one on bipolar disorder (BP), and one that
      comprised SZ and BP under the hypothesis of a susceptibility locus common to both
      in major psychoses (common locus, CL). The results of parametric analyses did not
      support a major gene hypothesis. However, in one large mixed pedigree (#151), we
      observed with the common locus phenotype (CL) lod scores of 2.49 and 2.15,
      respectively, at the D6S296 and D6S277 loci under a dominant model. Our data
      suggest the presence of a potential vulnerability locus at 6p24-22 that could be
      related to both schizophrenia and bipolar affective disorder. These results may
      be seen as congruent with former studies that used schizoaffective as well as
      schizophrenia diagnoses as entry criteria for the affected families, and used an
      affection definition that comprised affective psychoses as well as schizophrenia.

PMID- 9184317
TI  - Linkage study of chromosome 6p in sib-pairs with schizophrenia.
AB  - Following reports of linkage between schizophrenia and markers in the chromosomal
      region 6p24-22 we have studied nine microsatellite markers spanning 40 cM of this
      region in our sample of 102 affected sibling pairs from 86 families. Allele
      sharing identity by descent was examined using likelihood based sib-pair analysis
      as implemented by the program SPLINK. No evidence for linkage was obtained and
      the highest lod score was only 0.192 for D6S309. We conclude that if there is a
      susceptibility locus for schizophrenia in this region then its effect size is so
      small as to render our study insufficiently powerful to detect it.

PMID- 9184318
TI  - Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and
      bipolar I disorder patients: tentative association between B37 and schizophrenia.
AB  - We have genotyped unrelated French Alsatian schizophrenic and bipolar I disorder
      (BPD) patients and matched controls for the polymorphic CAG repeats within the
      genes for spinocerebellar ataxia type 1 (SCA1) and dentatorubral-pallidoluysian
      atrophy (B37), in order to test their possible involvement in these disorders. No
      alleles with abnormally expanded repeats were found in either gene in patients
      and controls. Differences in allele and genotype frequencies for the SCA1 CAG
      repeat between patients and controls were not significant, thus providing no
      support for its role as a possible positional candidate gene for schizophrenia
      and BPD in our patients. Chi square testing revealed a significant result (P =
      0.019) for an association between the B37 CAG repeat on chromosome 12p and
      schizophrenia. This result was more significant when only schizophrenics with a
      positive family history were compared with controls (P = 0.0001). The frequencies
      of alleles with 14, 12, and 15 CAG repeats differed the most, respectively,
      between schizophrenics and controls. When choosing the median of the B37 allele
      distribution (15 CAG repeats) as a threshold, there were significantly more
      controls than schizophrenics in the group with longer alleles (15 or more
      repeats) and more schizophrenics with shorter alleles (P = 0.002 by Fisher exact
      test). No particular genotype was associated with schizophrenia. This result
      possibly indicates linkage disequilibrium with another locus on chromosome 12p
      and therefore deserves further attention. No association was found between the
      B37 CAG repeat and patients with BPD.

PMID- 9184319
TI  - Additional clinical and cytogenetic findings associated with Rett syndrome.
AB  - An analysis of all aphidicolin-inducible breakpoints has been carried out in PHA
      stimulated T-lymphocytes of five patients with classical Rett syndrome, their
      mothers and a group of age matched controls. Observed breakpoints were divided
      into two groups: common, rare, and those recorded by others but not assigned as
      fragile sites by CCM92 and a group of non-specified breakpoints recurrently found
      in our ongoing study of fragile sites. In addition cooccurrence of trisomy X in
      one patient and de novo pericentromeric inversion on chromosome 2 in another Rett
      syndrome patient are reported. The co-occurrence with the Tourette syndrome in
      two of our families, and the fact that both Rett and Tourette syndrome are
      associated with movement disorders, possible dopaminergic hypersensitivity and
      increased chromosomal fragility in subsets of fragile sites, may suggest a
      possible avenue for further research. The cytogenetic findings indicate that both
      X-linked and autosomal regulatory region(s) may be part of a complex genetic
      alteration in association with Rett syndrome.

PMID- 9184320
TI  - Genes for interleukin-2 receptor beta chain, interleukin-1 beta, and
      schizophrenia: no evidence for the association or linkage.
AB  - We studied a CA repeat polymorphism of the interleukin-2 receptor beta chain (IL
      2RB) gene and a C/-514/T variation of the interleukin-1 beta (IL-1B) gene in
      Japanese schizophrenia patients. Both a case-control association study (54
      patients and 54 controls) and a linkage study using six multiplex families (the
      number of the affected > or =4 in each family) were employed. No evidence for the
      association or the linkage was obtained either for the IL-2RB or IL-1B gene.

PMID- 9184321
TI  - A study of genetic association between manic-depressive illness and a highly
      polymorphic marker from the GABRbeta-1 gene.
AB  - We report on an association study between a tetranucleotide repeat polymorphism
      in the GABR beta1 gene and manic-depressive illness in a Spanish population. This
      gene may be an important candidate for bipolar affective disorders since severe
      GABergic alterations have been described in patients. Although our results do not
      reveal a clear evidence for association between manic-depressive illness and GABR
      beta1, we have found significant differences between patients and controls in the
      female subpopulation.

PMID- 9184322
TI  - A comparative and historical review of culture methods for vertebrates.

PMID- 9184323
TI  - Technique as the basis of experiment in developmental biology. An interview with
      Denis A.T. New. Interview by Juan Arechaga.

PMID- 9184324
TI  - Development of sidedness of asymmetric body structures in vertebrates.

PMID- 9184325
TI  - Mammalian craniofacial embryology in vitro.
AB  - Our review demonstrates that the whole embryo culture system established by New
      and his colleagues, in combination with beneficial fluorescent dye cell-tracing
      techniques, has greatly contributed to many advancements in the field of
      mammalian craniofacial embryology, especially with regard to elucidating the
      developmental behavior of cephalic crest cells. In addition, based on recent
      results, further combining whole embryo culture with mandibular organ culture
      methods has allowed us to trace cranial crest cells for a much longer
      developmental period, i.e., presently up to the cap stage in odontogenesis.

PMID- 9184326
TI  - Surgical manipulation of mammalian embryos in vitro.
AB  - Whole-embryo culture systems are useful in the fields of not only embryology but
      also teratology, toxicology, pharmacology, and physiology. Of the many advantages
      of whole-embryo culture, we focus here on the surgical manipulation of mammalian
      embryos. Whole-embryo culture allows us to manipulate mammalian embryos,
      similarly to fish, amphibian and avian embryos. Many surgical experiments have
      been performed in mammalian embryos in vitro. Such surgical manipulation alters
      the destiny of morphogenesis of the embryos and can answer many questions
      concerning developmental issues. As an example of surgical manipulation using
      whole-embryo culture systems, one of our experiments is described. Microsurgical
      electrocauterization of the deep preaxial mesodermal programmed cell death zone
      (fpp) in the footplate prevented the manifestation of polydactyly in genetic
      polydactyly mouse embryos (Pdn/Pdn), in which fpp was abolished.

PMID- 9184327
TI  - Mechanisms of normal and abnormal neurulation: evidence from embryo culture
      studies.
AB  - The method of whole embryo culture has been used extensively in analyzing the
      mechanisms underlying formation of the mammalian neural tube. These studies have
      provided insight into the cell lineage of the various tissues that comprise the
      neurulation stage embryo, the role of microfilaments, extracellular matrix and
      cell proliferation in the morphogenetic events of neural tube closure and the
      action of specific genes and gene products in establishment of the nervous
      system. This information is of considerable importance not only as a means of
      elucidating the processes of normal embryogenesis but also to shed light on the
      pathogenesis of important human birth defects.

PMID- 9184328
TI  - Prorhombomeric subdivision of the mammalian embryonic hindbrain: is it
      functionally meaningful?
AB  - The technique of whole embryo culture has made significant contributions to
      understanding the mechanisms of morphogenesis in mammalian embryos, especially
      with respect to cranial neurulation and neural crest cell migration. This study
      traces the fate of two specifically mammalian structures, the preotic and otic
      sulci. Their formation at the 1/2- and 3-somite stages respectively, divides the
      hindbrain neuroepithelium into prorhombomeres A, B and C. The preotic sulcus is a
      deeply recessed structure that forms the rostral boundary of expression of both
      Hoxb-2 and the first domain of Krox-20. The otic sulcus is a shallow concavity in
      which the second Krox-20 domain is expressed. DiI labeling followed by whole
      embryo culture confirmed that the later fate of the preotic sulcus is the
      rhombomere 2/3 boundary, and the fate of the otic sulcus is the cranial part of
      rhombomere 5. Structurally, the preotic and otic sulci show no specialization
      with respect to actin, tubulin or proteoglycans, but their maintenance depends on
      contact with the subjacent mesenchyme. Their formation is inhibited by exposure
      of embryos to retinoic acid prior to the onset of somitic segmentation,
      indicating that the molecular events governing prorhombomeric subdivision of the
      hindbrain are retinoic acid-sensitive. The preotic sulcus may be essential for
      neuroepithelial cell movement towards and into the rapidly enlarging forebrain;
      the otic sulcus may simply delineate the caudal boundary of prorhombomere B, an
      area with a discrete neural crest cell population discontinuous with those
      rostral and caudal to it. Understanding the positional relationships of the
      preotic and otic sulci to later rhombomeric segments makes them useful landmarks
      for experimental purposes, but there is no evidence that prorhombomeres are
      functionally significant as the precursors of rhombomeric segments.

PMID- 9184329
TI  - Computer-aided 3-D reconstruction of serially sectioned mouse embryos: its use in
      integrating anatomical organization.
AB  - This paper reviews recent work on a project that uses a computer-aided approach
      for making 3-D reconstructions of serially sectioned mouse embryos (the digital
      mouse). The captured images are aligned using a warping program so that almost
      perfect alignment of adjacent sections is achieved with minimal deformation. The
      sections that are viewed on the computer screen are in fact computer-generated
      grey-level images with a resolution of about 10 microm. The reconstructed embryo
      may then be resectioned in any plane to simulate as near as possible an exact
      match on the computer screen to the viewer's own material. Individual anatomical
      domains may then be painted in different colors, and these domains may be
      selected by querying the textual database containing anatomical and other
      information. Further, it is now possible to generate 3-D images of individual
      anatomically-discrete components or related sets of components of a particular
      system in isolation from the rest of the embryo, or, if required, against a
      'ghost-like' image of the intact embryo, or specific parts of an embryo. In the
      article, examples are given of the use of the system in interpreting the
      vascular, gut and paraxial mesoderm systems, while both the advantages and
      disadvantages of this approach are also discussed. The eventual aim will be to
      provide 3-D reconstructions of mouse embryos from fertilization up to 14 days
      postcoitum of development. When completed, this project will allow the accurate
      spatial mapping of gene-expression and cell lineage data onto the digital Atlas
      of normal mouse embryonic development.

PMID- 9184330
TI  - Reflections on the biology of embryonic stem (ES) cells.
AB  - Remarkably little is known about mammalian embryonic stem (ES) cells despite
      their very widespread use in studies on gene disruption and transgenesis. As yet,
      it is only in the mouse that lines of ES cells which retain the ability to form
      gametes following reintroduction into the early conceptus have been obtained.
      Even in this species, most strains have so far proved refractory to the
      derivation of such cell lines. Apart from persisting ignorance as to how the
      various procedures that have been claimed to improve success actually do so, even
      the tissue of origin of ES remains uncertain. Furthermore, it is doubtful whether
      retention of pluripotency or expression of so-called "stem cell" marker molecules
      provide an adequate basis for classifying cells as genuine ES cells. This is
      because epiblast cells, their presumed precursors, lose the capacity to colonize
      the preimplantation conceptus well before they become restricted in the types of
      cell they can form or cease to express such marker molecules. In addition, it has
      yet to be established whether heterogeneity of cells within individual ES cell
      lines arises entirely during culture or is at least partly attributable to lack
      of homogeneity among their precursors. Finally, it has yet to be explained why ES
      chimeras evidently differ from those obtained by combining cells from different
      conceptuses in showing greater variation between tissues in the level of
      chimerism.

PMID- 9184331
TI  - Comparative stem cell biology.
AB  - This review collates data from a range of stem cells studies in an attempt to
      bring together an overall view of stem cell biology. Data from hemopoietic,
      keratopoietic, hepatopoietic and neuropoietic stem cells are presented. The
      developmental and cell biology of each system is discussed in an attempt to
      develop a comparative view of stem cell biology. Comparisons are drawn in the
      areas of clonal analysis, surface antigen expression, adhesion molecules and
      cytokine interactions. Where appropriate the role of embryonic stem (ES) cells is
      also considered in the developmental biology of the cells in question.

PMID- 9184332
TI  - Recent scientific and medical advances in assisted human conception.

PMID- 9184333
TI  - Legal, ethical and historical aspects of assisted human reproduction.

PMID- 9184334
TI  - The use of whole rat embryo cultures to identify and characterize causes of
      reproductive failure.
AB  - The most important problem facing human teratology today is to identify the
      actual causes of this health problem. We have used cultures of whole rat embryos
      to address this problem using blood sera from individuals at risk as embryo
      culture media for this purpose. Through serum fractionations and nutrient
      supplementations to the serum we have studied drugs (dilantin, valproic acid),
      nutrient deficiencies (methionine) and an embryotoxic autoantibody to the protein
      laminin. In addition to identifying these factors it has been possible to address
      their mechanisms of action and to provide recommendations for treatment.

PMID- 9184336
TI  - Carbon monoxide and the embryo.
AB  - Mammals are homeotherms and expend considerable energy maintaining their body
      temperatures. The temperature of a mammalian embryo on the other hand is
      maintained by the mother and the embryo can devote its metabolic energy to growth
      and development. The mammalian embryo is acting as a poikilotherm and its energy
      needs are thus considerably less than if it were a comparably sized homeotherm.
      The energy requirements of the preimplantation rat embryo are generated by
      anaerobic metabolism. As it grows, aerobic metabolism develops. In culture, the
      addition of carbon monoxide to the perfusing gas for early rat embryos has a much
      smaller effect than decreasing the oxygen concentration. Carbon monoxide appears
      to be a relatively mild toxicant until the embryo is much larger, is depending
      much more on transport of oxygen by red blood cells, and the fraction of required
      metabolic energy produced by anaerobic metabolism has become quite small. The
      effect from smoking during gestation may be either by the concomitant reduction
      in food intake or a more direct toxic effect from some components in the smoke.
      Carbon monoxide does not seem to be the culprit. The possible mitigating effect
      of a compensatory increase in fetal hematocrit in response to any hypoxia must
      also be considered. Humans have no yolk sac placenta as rodents do, but if the
      switch from anaerobic to aerobic metabolism is correlated with the stage of
      development, then carbon monoxide exposure should not represent any significant
      risk to the human embryo until later in gestation.

PMID- 9184335
TI  - The evaluation of developmental toxicity of chemicals exposed occupationally
      using whole embryo culture.
AB  - The purpose of this study was to employ the whole embryo culture (WEC) system to
      evaluate the developmental toxicity of industrial chemicals. Five chemicals
      including lead, cadmium, vinyl chloride, 1,2-dichloroethan, and carbon disulphide
      were tested in our laboratory both in vitro and in vivo (except lead). In vitro
      studies showed that cadmium and lead were teratogenic in the rat; whilst carbon
      disulphide, 1,2-dichloroethan and vinyl chloride mainly induced embryo growth
      retardation. The in vitro effects on development of the five industrial chemicals
      were similar to the effects in vivo. The in vitro effects were studied by three
      different exposure routes, direct exposure--chemicals added to the culture
      medium; indirect exposure--serum prepared from treated rats then used as culture
      medium, and pre-exposure--embryos treated maternally then explanted into control
      (untreated) culture medium. Comparing these three different exposure routes
      suggests that the last exposure route is the most effective when using WEC to
      evaluate developmental toxicity of industrial chemicals. The effects on embryo
      development of culturing in sera prepared from subjects occupationally exposed to
      antineoplastic drugs (ADs) was also tested by the WEC system. Embryos were
      cultured with human serum that was thought to contain ADs or ADs' metabolic
      materials (serum taken from nurses routinely handling ADs), to evaluate the
      effects of ADs on embryo development. Embryos (9.5-day) cultured with serum from
      11 female nurses who had been handling ADs for 2-17 years in the oncology
      department all survived, but showed slight growth retardation. Embryos cultured
      with serum from 30 healthy and unexposed people served as controls and embryo
      development in their serum was normal.

PMID- 9184337
TI  - Mouse embryos in culture: models for understanding diabetes-induced embryopathies
      and gene function.
AB  - Both the metabolic studies on diabetes and the genetic studies using antisense
      oligodeoxynucleotides clearly demonstrate the importance and usefulness of rodent
      whole embryo culture. Without this technique, these studies would be impossible
      and, consequently, our knowledge of both normal and abnormal development would
      not be as advanced as it is today. The culture system fills a unique niche in
      studies in the fields of developmental biology and teratology and these sciences
      would have been less well served without Dr. New's contribution.

PMID- 9184338
TI  - Effects of excess glucose on mammalian post-implantation embryos.
AB  - Studies on the effects of excess glucose on mammalian post-implantation embryos
      grown in culture are reviewed and selected examples of these studies are
      discussed to demonstrate the value, and the limitations, of the embryo-culture
      system. By use of culture techniques the precise concentrations of exogenous
      glucose causing morphological and biochemical changes are defined for a range of
      developmental stages in both rat and mouse embryos. The critical window of
      exposure is known and the morphological, cellular and biochemical changes
      associated with hyperglycemic culture are described. The effects of hyperglycemic
      serum are briefly compared with those of serum prepared from diabetic rats and
      the contribution of the high glucose concentrations to the embryopathic effects
      of the "diabetic" serum is assessed. The advantages and the limitations of the
      culture system are discussed.

PMID- 9184339
TI  - Glucose absorption and utilization by rat embryos.
AB  - There is little doubt that glucose plays a significant nutritional role in early
      somite embryos. The high glucose utilization of anaerobic glycolysis drops as the
      activity of the Kreb's cycle and terminal electron transport increase.
      Concurrently, maturation of mitochondrial cristae and dependence on oxygen supply
      are taking place. The neuroepithelium of the early somite rat embryo responds in
      vitro during culture by microvilliar lengthening when exposed to glucose levels
      of 50 mg/dl or more. At lower glucose concentrations both in whole embryo culture
      and inside the closed neural tube the microvilli are shorter. Lengthening of the
      microvilli at room temperature is produced only by d-glucose and 2-deoxyglucose,
      two hexoses that are absorbed and phosphorylated. Cytochalasin D which disrupts
      actin polymerization causes ballooning of the microvilli. A role of this
      microvillar elongation in degenerative changes seen in uncontrolled diabetes and
      on function of the immune system is proposed. The amniotic cavity is one major
      portal of entry for glucose during the early somite embryo stage. The 7-fold
      increase in volume of the amniotic cavity after day 10 allows the rat embryo to
      convert its axis from dorsal to ventral flexion.

PMID- 9184340
TI  - Investigations into mechanisms of amino acid supply to the rat embryo using whole
      embryo culture.
AB  - The technique pioneered by D.A.T. New for the in vitro culture of early post
      implantation rat embryos has been used to study nutritional mechanisms during
      early organogenesis. The results indicate that the principal route for amino acid
      supply to the 8.5- to 11.5-day embryo involves the endocytosis of proteins into
      cells of the visceral yolk sac endoderm, their digestion in lysosomes, and
      transmission of the amino acids to the growing embryo. Free amino acids
      constitute a comparatively unimportant source. Inhibition of either endocytosis
      or intralysosomal proteolysis diminishes amino acid supply to the embryo, and
      this can result in embryonic death or maldevelopment during organogenesis.

PMID- 9184341
TI  - The role of exogenous growth-promoting factors and their receptors in
      organogenesis.
AB  - The mechanisms involved in the regulation of early embryonic development are
      poorly understood. Certain growth promoting molecules are known to be produced
      within the embryo itself. It is clear, however, that at the early stages of
      embryonic development, many additional growth promoting factors have to be
      provided by the maternal system. Since the levels of factors such as epidermal
      growth factor and insulin in the maternal circulation are not linked with
      gestational age of the offspring, it is likely that regulation of receptors in
      the embryonic tissues may provide the key to the regulation of development. The
      expression of any receptor may depend on its synthetic rate, turnover or its
      distribution between the cell surface and intracellular pools. The study of the
      role of exogenous growth promoting molecules and receptor distribution and
      regulation for such growth factors, in particular insulin, insulin-like growth
      factor-I and epidermal growth factor, in embryos has been addressed using whole
      embryo culture, supported by anembryonic yolk sac culture and intravitelline
      injection of rat embryos.

PMID- 9184342
TI  - A review of the contribution of whole embryo culture to the determination of
      hazard and risk in teratogenicity testing.
AB  - Whole embryo culture appears to be an excellent method to screen chemicals for
      teratogenic hazard. Compared to in vivo testing it is cheap and rapid and does
      not involve experimentation on live adult animals. Also in the important area of
      risk estimation whole embryo culture offers distinct advantages over in vivo
      teratogenicity testing. Adverse embryonic outcomes (malformations or
      embryotoxicity) are directly related to the serum concentration of the compound
      being tested and can be compared to the serum concentration in the human. A
      similar comparison is not possible after in vivo testing because for most
      compounds there are major pharmacokinetic differences between humans and
      experimental animals. In vivo testing is also limited by the possibility that
      metabolites that occur in the human do not occur in the test animal. This problem
      can be overcome in the in vitro system by adding the metabolite directly at the
      desired concentration either with or without the parent compound. There is only
      one major disadvantage to in vitro testing and that is the limited period of
      embryogenesis that is undertaken in the commonly used culture system. This
      restricts the range of malformations that can be induced and may render the
      testing system unsuitable for compounds that are likely to exert their major
      toxicological effect late in gestation. Any evaluation of whole embryo culture
      for hazard and risk assessment in teratology must take into account the limited
      value of currently used in vivo methods. Over 2000 chemicals have been reported
      to be teratogenic in experimental animals exposed in vivo (Shepard, Catalog of
      Teratogenic Agents, 1989). In comparison only about 20 chemicals are known to
      cause birth defects in the human. This large number of in vivo false-positive
      cannot easily be distinguished from true-positives. In this respect in vivo
      testing is severely deficient. The embryo culture testing system would also be
      expected to produce many false-positives; but by comparing effective drug
      concentrations with human therapeutic concentrations they can be differentiated
      from true-positives. The most serious deficiency for an in vivo or in vitro
      teratogenicity testing system would be false-negatives. This has not been a
      problem in the validation of in vitro testing so far (except perhaps
      procarbazine), but difficult drugs such as thalidomide were not included.
      Thalidomide remains an important index chemical because it is not teratogenic in
      rats or mice but is teratogenic in the rabbit and human. It is likely that these
      species differences are due to metabolic differences between species and it is
      possible that if the proximate teratogen/s of thalidomide were identified they
      would be teratogenic in rat embryo culture. Whole embryo culture remains a very
      powerful technique that should continue to contribute to the determination of the
      safety of drugs and other chemicals during pregnancy.

PMID- 9184343
TI  - Genetic determinants of teratogen-induced abnormal development in mouse and rat
      embryos in vitro.
AB  - The response of an embryo to a teratogenic treatment is often critically
      dependent on its genetic makeup. However, in conventional in vivo studies of gene
      teratogen interactions it may be difficult to distinguish between the effects of
      genes that are carried by the embryo and those that are carried by the mother. It
      is likewise not easy to determine whether an observed interaction is between a
      particular gene and the parent compound administered, or whether it is with a
      metabolite that has been generated by the maternal system. The use of whole
      rodent embryo culture offers certain advantages in the study of gene-teratogen
      interactions. Not only can the effects of metabolism and the maternal genotype be
      more carefully controlled, but the stage of development at which embryos of
      different genotypes are exposed can be matched. Rodent whole embryo culture has
      been used to a limited extent to study interactions between single gene mutations
      and teratogenic treatments, variations in responses of different strains to
      teratogens, as well as species differences in response to teratogens. These
      studies point to the need to precisely control the stage of development at the
      time of treatment in order to be able to make valid comparisons. But, even more
      important, they highlight the versatility of the whole embryo culture technique,
      and underscore the need for its wider use in evaluating the relative contribution
      of genes and environment to abnormal embryonic development.

PMID- 9184344
TI  - Hyperthermia, teratogenesis and the heat shock response in mammalian embryos in
      culture.
AB  - Hyperthermia is a recognized teratogen in animals and there is strong evidence
      that it also causes significant damage to human embryos. Studies with induced
      hyperthermia in pregnant animals defined the defects which are produced, the
      susceptible stages of development, and threshold doses of heat required to cause
      defects. The in vivo experiments lacked precision because of variability of
      embryonic development at a given conceptual age, varying maternal responses to
      agents causing temperature elevations, the difficulty in measuring embryonic
      temperature and the possibility that defects were caused by toxic changes in
      maternal metabolism. These variables were eliminated by the use of
      postimplantation whole rat and mouse embryo cultures, which were exposed to
      various doses of heat at closely defined stages of development. The studies
      showed that heat acts directly on embryos and that elevations of 2 degrees C and
      greater sustained over early rat organogenesis cause defects mainly by causing
      apoptotic cell death especially in the developing central nervous system. A
      moderate, non damaging exposure is followed within 15 min by protection for up to
      8 h against a more severe and otherwise teratogenic exposure. The protective heat
      shock response is accompanied by a reduction of normal protein synthesis and
      concurrent synthesis of heat shock proteins (HSP90, 71, 47, 27). Most HSP in
      these families are also present constitutively in embryos, probably having
      important roles in protecting newly synthesized proteins from aggregation and
      facilitating folding into their normal functional configurations. The appearance
      of induced HSP and hsp mRNA at known sites of thermal damage suggests a
      protective role. Heat induced cell death by apoptosis is a feature of teratogenic
      damage to the developing brain. Apoptosis could be a by-product of a damaging
      heat exposure because of a priority favoring induction of the heat shock response
      over the normal gene program for organogenesis, survival being achieved at the
      expense of normal development.

PMID- 9184345
TI  - Gene expression domains as markers in developmental toxicity studies using
      mammalian embryo culture.
AB  - We are examining the hypothesis that expression domains of developmental control
      genes may be informative markers in mammalian embryo culture studies of
      developmental toxicity. Expression domains might be altered directly by chemical
      exposure, or might reflect developmental abnormality prior to any overt
      morphological defect. Whole-mount in situ hybridization using digoxygenin-labeled
      RNA probes was used to monitor the regions of expression of Hoxb-4, Pax-3 and Emx
      2. These genes were selected because of their different restrictions within the
      developing CNS; Hoxb-4 for its anterior margin in the hindbrain, Pax-3 for its
      dorso-ventral pattern in the spinal cord, and Emx-2 for being restricted to a
      portion of the forebrain. Valproic acid was used as a prototype developmental
      toxicant because of its known actions on neural tube closure and on segmentation.
      For patterns of expression, we made three comparisons, between: rat in vivo
      developed embryos and published descriptions for mouse; rat cultured and in vivo;
      control and valproate exposed. For these genes, there were no differences between
      domains of expression in rat and mouse, nor between rat cultured and in vivo
      embryos. In valproate-exposed embryos, some domains were spatially abnormal, for
      example Pax-3 in the neural crest, but this was coincident with structural
      defects induced by the treatment. There was no indication, for these three genes,
      and this teratogen, that treatment caused any shifts in boundaries of expression,
      nor induced any ectopic domains, even though exposures induced overt
      malformation.

PMID- 9184346
TI  - Postimplantation mouse embryos cultured in vitro. Assessment with whole-mount
      immunostaining and in situ hybridization.
AB  - The postimplantation embryos of rodents have been particularly convenient to
      study in culture using the whole embryo culture (WEC) system developed by New.
      Two serious limitations of the method will be illustrated in the present paper
      and proposals will be made to improve the quality of the information. The first
      limitation is that the developmental period amenable to culture has not been
      significantly extended in recent years. In the present paper, we show that the
      culture of mouse presomitic stages for 48 h leads to poorly reproducible results
      and frequent dysmorphogenic embryos. We also show that early somite stages
      cultured for 54 h or less have a normal growth and differentiation. In contrast,
      the culture of these embryos for 72 h results in subtle abnormalities of the head
      and the first branchial arch. The second limitation is that the gross morphology
      and histology are often not informative enough to distinguish between overall
      toxicity and developmental toxicity. We suggest some improvements by the
      association of WEC with two specific techniques: 1) whole-mount immunostaining of
      sensory ganglia and nerves and 2) in situ hybridization on histological sections
      using molecular probes for some developmental genes. Embryos reaching about the
      30 somite stage at the end of the culture were processed for whole-mount
      immunostaining of sensory ganglia and nerves. We show that these structures are
      very sensitive to the noxious effects of HgCl2 and valproate. Both developmental
      retardations and dysmorphogeneses of the cervical ganglia and nerves were
      observed. Embryos were also exposed in vitro to low concentrations of all-trans
      retinoic acid (AT-RA) and processed for in situ hybridization with radiolabeled
      anti-sense RNA probes for the Hoxb-1 and Hoxb-2 developmental genes. Three
      dimensional reconstructions of the expression domains were performed. The data
      show that AT-RA induces ectopic expression domains of Hoxb-1. Our experiments
      demonstrate that techniques such as immunostaining and in situ hybridization can
      significantly expand the information obtained from whole postimplantation embryo
      culture.

PMID- 9184347
TI  - The effect of antisense oligonucleotides to Cdx2 on the development of mouse
      embryos in vitro.
AB  - The Drosophila homeobox gene caudal is thought to play a role in segmentation and
      the formation of posterior structures in the fly. One of the mouse homologs,
      Cdx2, is first expressed in embryonic tissue at 8.5 days, being detected in the
      tail bud, neural tube and hindgut. To gain insight into the role of Cdx2 in mouse
      development, we have applied antisense technology to the mouse embryo culture
      system. Two antisense and two mismatch (control) oligonucleotides were injected
      into the amniotic cavity of 5-7 somite embryos, thus coming into direct contact
      with the dorsal surface of the embryo. The results showed that all constructs
      were biologically active, the nature of the abnormalities produced probably
      reflecting the developmental stage at which the embryo was exposed. However, the
      antisense constructs were clearly more potent than their mismatch controls and we
      conclude that some specificity of action is responsible for this effect. In our
      view, this does not necessarily imply that Cdx2 has a direct role in brain
      morphogenesis.

PMID- 9184348
TI  - Early chick embryos in vitro.
AB  - In 1955, Denis New described a technique for the in vitro culture of early avian
      embryos that has formed the basis for nearly all of the experimental
      embryological studies performed on these species since that day. Many
      modifications to this technique have also been described in these four decades
      for specific experimental purposes. Here, we review the effects of some
      parameters that appear to be important for different aspects of the growth of
      embryos in this type of culture, and conduct a small experimental comparison
      between different modifications of the technique as described by various authors.
      We conclude that the original technique still compares favorably with its
      alternatives.

PMID- 9184349
TI  - Chick noggin is expressed in the organizer and neural plate during axial
      development, but offers no evidence of involvement in primary axis formation.
AB  - We have cloned and examined the early developmental expression of the chick
      homolog of noggin, a gene originally isolated in Xenopus that can dorsalize
      gastrular mesoderm and induce anterior neural tissue from gastrular ectoderm when
      expressed experimentally. Chick noggin is expressed at relatively low levels, but
      at sites equivalent to those seen in amphibian development, namely Hensen's node
      and the endo- and mesodermal head process. There is also diffuse expression in
      the early CNS, centered on the ventral midline, and later hindbrain-associated
      expression. Since the earlier of these expression sites are consistent with
      endogenous organizer functions suggested by the properties of the protein in
      Xenopus experiments, we have used recombinant mammalian Noggin protein secreted
      by CHO cells in tests for developmental disturbance on the early gastrula-staged
      chick blastoderm. Comparable tests sensitively detect effects, on chick, of
      various other secreted proteins that simulate or replicate early developmental
      signals in Xenopus. We have been unable to observe such effects with a range of
      Noggin concentrations including those that dramatically dorsalize Xenopus ventral
      marginal zones. To illustrate effects observed in such tests with secreted
      proteins active on early stages, we show results with the known Xenopus
      ventralizer Bone Morphogenetic Protein 4 (BMP-4).

PMID- 9184350
TI  - Development in vitro of Marsupials: a comparative review of species and a
      timetable of cleavage and early blastocyst stages of development in Monodelphis
      domestica.
AB  - The development of marsupial oocytes and embryos in vitro is reviewed. Most
      stages of development have been cultured successfully, usually in a complex
      medium with added fetal calf serum. Simpler media without added serum have been
      developed for fertilization and cleavage in vitro. Culture systems have been
      established for oocyte maturation and fertilization in the grey short-tailed
      opossum and for cleavage from the zygote to the early expanding unilaminar
      blastocyst in a number of other marsupials. Survival in vitro of the unilaminar
      and early bilaminar blastocyst stages is limited in all species examined. In
      contrast, late bilaminar, trilaminar, embryonic and fetal stages develop at rates
      approximating those in vivo. More stages have been cultured successfully in
      Sminthopsis macroura than in any other species. It has been cultured from the
      late bilaminar blastocyst to within 18 h of birth. Stages of cleavage and
      unilaminar blastocyst formation of Monodelphis domestica timed by videotaping
      mating animals, proceeded at similar rates in vivo and in vitro. As in other
      marsupials, cleavage in this opossum is characterized by a polarized conceptus.
      This polarity is expressed in the distribution of organelles in the zygote and
      the localization of secretion of the extracellular matrix material into the
      cleavage cavity and of the initial cell-zona attachment. Because cell-cell
      adhesion follows cell-zona adhesion, a unilaminar blastocyst forms without the
      development of an intervening morula stage.

PMID- 9184352
TI  - Chronic hepatitis B: the therapeutic challenge.

PMID- 9184351
TI  - The aquatic vertebrate embryo as a sentinel for toxins: zebrafish embryo
      dechorionation and perivitelline space microinjection.
AB  - Pollution of aquatic ecosystems poses a serious threat to aquatic organisms and
      ultimately the entire ecosystem. Understanding how a toxin affects embryonic
      development is key to determining the risk a pollutant represents to the
      environment. Extraembryonic membranes, such as the chorion of fish eggs, provide
      a protective barrier between the embryo and the environment. Although the fish
      chorion excludes many chemical pollutants, some noxious agents can still gain
      access to the aquatic embryo. Therefore a monitoring system that tests the
      effects directly upon the embryo must be established. Although exposure to a
      single toxin in the laboratory can determine the concentration at which a
      pollutant becomes a health or environmental hazard, embryos and adults in nature
      are not merely affected by a single chemical, but are exposed to mixtures of
      different pollutants. Zebrafish (Danio rerio) and medaka (Oryzias latipes)
      embryos were employed for the rapid observation of the effects of single
      chemicals and chemical mixtures on development. Using dechorionation and a
      perivitelline space microinjection system, the embryos were effective sentinels
      for low concentrations of aquatic pollutants. The developmental effects of small
      quantities of toxins were observed. Embryos treated during the late gastrula
      stage of development with hexachlorobenzene (HCB); 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD); toluene; benzene; or mixtures of these chemicals developed
      cardiovascular abnormalities. The zebrafish dechorionation exposure technique,
      Micro Intrachorionic Zebrafish Embryo Live Laboratory test, was especially
      effective in testing the pollutant mixtures. Combinations of both TCDD and
      benzene (as well as the toluene and benzene combinations) were tested and the
      mixtures acted synergistically; the combinations were more toxic than either
      chemical by itself. Hexachlorobenzene- and TCDD-treated embryos tested positively
      for expression of cytochrome P450 1A indicating that the cytochrome metabolic
      pathways were already functional in these early embryos, and suggested that a
      product of the cytochrome system may be involved in HCB and TCDD pollution
      associated cardiovascular defects.

PMID- 9184353
TI  - The role of macrolides in Streptococcus pyogenes pharyngitis.

PMID- 9184354
TI  - In-vitro sensitivities and treatment of less common mycobacteria.
AB  - There are very few new agents available for the treatment of infections due to
      the less common mycobacteria. There have been very few systematic studies of in
      vitro activity and fewer clinical trials. Yet such mycobacteria are an important
      cause of serious disease and often conventional antimycobacterial agents are
      unsuitable either because of in-vitro resistance of the pathogen concerned, or
      toxicity of one of the components of drug regimens. At present, newer macrolides
      and quinolones offer promise, but there is a need to extend the in-vitro studies
      already under way of newer agents against Mycobacterium avium and/or
      Mycobacterium tuberculosis, to the other, less common mycobacteria. The
      benzoxazinorifampicins, the oxazolidinones and the acridinones may prove to be of
      clinical value. In addition to more information on the in-vitro activity of newer
      agents, alone and in combination, based on systematic studies involving larger
      numbers of mycobacterial strains, we need clearer clinical information to enable
      therapeutic regimens to be formulated and validated. The British Thoracic Society
      study is but a first step. There need to be more.

PMID- 9184355
TI  - In-vitro microbiological assessment of a new penem, Men 10700.
AB  - The in-vitro antibacterial activity of Men 10700, a novel penem, has been
      compared with that of ritipenem, ciprofloxacin, amikacin, cefotaxime and co
      amoxiclav against 539 strains taken from 17 genera. Men 10700 was most active
      against staphylococci and streptococci (MIC90 < 0.5 mg/L), slightly less active
      against Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Citrobacter
      spp., Moraxella catarrhalis and peptostreptococci (MIC90 0.5-2 mg/L), moderately
      active against Enterococcus faecalis, members of the tribe Proteae, Serratia
      marcescens, Acinetobacter spp., clostridia and Bacteroides spp. (MIC90 4-16
      mg/L), and inactive against Pseudomonas aeruginosa, Stenotrophomonas maltophilia
      and Enterococcus faecium. Its antibacterial spectrum is thus slightly less broad
      than that of imipenem, but it compares favourably with an oral third-generation
      cephalosporin. Men 10700 was more active than ritipenem against many species,
      especially Enterobacter spp. and Citrobacter spp.

PMID- 9184356
TI  - In-vitro activity of lansoprazole against Helicobacter pylori.
AB  - Lansoprazole is a gastric parietal cell proton pump inhibitor that is also active
      against Helicobacter pylori in vitro. We aimed to investigate further the
      mechanism of its antimicrobial effect. The antimicrobial activity of lansoprazole
      and of its sulfenamide, a rearrangement product occurring spontaneously in acid
      environments, was studied by determining the MICs and MBCs for 11 cytotoxic and
      eight non-cytotoxic H. pylori strains and by measuring the rapidity of bacterial
      killing. The MIC90 and MBC90 were 2.5 mg/L and 10 mg/L, respectively, both for
      lansoprazole and for its sulfenamide. Cytotoxic strains were as susceptible as
      non-cytotoxic strains. The sulfenamide exhibited faster bactericidal activity.
      Lansoprazole did not inhibit the toxin-induced vacuolization of HeLa cells by a
      cytotoxic strain, hence its anti-H. pylori activity does not depend on inhibition
      of a v-ATPase-mediated, toxin-induced activity. Sulfenamide formation is likely
      to occur in vivo in the gastric environment, thus enhancing the bactericidal
      activity of the drug. Lansoprazole is likely to be useful, in association with
      antibiotics, in the treatment of H. pylori infection regardless of the
      cytotoxicity of the infecting strain.

PMID- 9184357
TI  - In-vitro susceptibility pattern of Candida lusitaniae and evaluation of the Etest
      method.
AB  - The antifungal susceptibility of 35 Candida lusitaniae isolates was determined in
      vitro by the National Committee for Clinical Laboratory Standards (NCCLS) M27-P
      macrodilution methodology. All the isolates were susceptible to ketoconazole,
      itraconazole and fluconazole. Of the 35 isolates, eight (23%) were resistant to
      flucytosine. For amphotericin B, M27-P yielded a narrow range of MICs (0.06-0.5
      mg/L). We therefore investigated the activity of this drug by reading MICs at 72
      h and by using alternative media, namely casitone complex medium (CCM) and
      antibiotic medium 3 (M-3). Reading at 72 h did not generate reproducible results.
      CCM and M-3 provided better discrimination between the isolates but did not
      change the rank order of the MICs. We thus concluded that all the isolates were
      susceptible to amphotericin B. We also conducted an evaluation with the Etest
      method according to the manufacturer's instructions with RPMI 1640 agar, CCM and
      the alternative semi-synthetic medium (SSM). For RPMI 1640, agreements +/-2
      dilutions were 58% for amphotericin B, 92% for flucytosine, 57% for ketoconazole,
      92% for fluconazole and 74% for itraconazole. CCM did not improve the agreement
      rates between the two methods but it led to better growth of all the isolates.
      The suitability of SSM was pointed out with itraconazole. The poor agreement
      rates for amphotericin B and ketoconazole call for further evaluation of the
      Etest method to assess several drug-organism combinations.

PMID- 9184358
TI  - Stereoselective interaction of SCH 39304, a triazole, with sterol 14alpha
      demethylase of Aspergillus fumigatus.
AB  - The inhibitory activity of SCH 39304 and its enantiomers on radial growth and on
      the target enzyme, sterol 14alpha-demethylase, in Aspergillus fumigatus was
      studied to assess the role of stereochemistry in the efficacy of the drug. SCH
      39304 and the RR(+) enantiomer were active in inhibiting the growth while no
      inhibition in the growth was observed with the SS(-) enantiomer. The MIC of SCH
      39304 for the growth was about twice that of the RR(+) enantiomer. The
      differences in IC50s of SCH 39304 and its enantiomers for cell-free ergosterol
      biosynthesis correlated with their variations in MICs and type II binding spectra
      indicated the SS(-) enantiomer failed to bind to microsomal P450. These results
      show that the difference between SS(-) and RR(+) enantiomers in interacting with
      the target enzyme is the cause for significant difference in the potency between
      these two forms.

PMID- 9184359
TI  - Decreased susceptibility to antibiotic killing of a stable small colony variant
      of Staphylococcus aureus in fluid phase and on fibronectin-coated surfaces.
AB  - The frequency of small colony variants of staphylococci associated with
      persistent, antibiotic resistant and relapsing infections is probably
      underestimated. These variants demonstrate decreased metabolism, leading to slow
      growth, increased resistance to cell-wall-active antibiotics, and decreased
      uptake of aminoglycoside antibiotics. This altered phenotype arises from defects
      in menadione and haemin biosynthesis resulting in impaired electron transport and
      decreased ATP concentrations. The recent acquisition of a stable small colony
      variant (SCV strain JB1), generated from strain 6850 of Staphylococcus aureus,
      allowed us to study the susceptibilities to antibiotic killing of parent and
      variant strains. Because differences in susceptibilities have been found between
      unattached and surface-adherent organisms, we tested both strains in solid and
      fluid-phase assays. Suspensions of SCV strain JB1 exposed to 8 x MIC of either
      oxacillin, vancomycin or fleroxacin, exhibited lower reductions in viable counts
      than the parent strain 6850, especially when high bacterial concentrations (1-2 x
      10(7) cfu/mL) of either strain were tested. Susceptibility to antibiotic killing
      of bacteria attached to fibronectin-coated coverslips was markedly influenced by
      their growing or nongrowing state on the surface. In the latter condition,
      surface-bound SCV organisms were highly resistant to the bactericidal action of
      oxacillin or vancomycin in contrast to the parental strain which was normally
      eliminated by each antimicrobial agent. In conclusion, the decreased
      susceptibility of the stable SCV strain of S. aureus to bactericidal
      concentrations of antibiotics may help to explain the persistence of such
      organisms in chronic infections.

PMID- 9184360
TI  - Non-gyrA-mediated ciprofloxacin resistance in laboratory mutants of Streptococcus
      pneumoniae.
AB  - Two strains of Streptococcus pneumoniae, M4 (NCTC 7465, type strain) and M5
      (clinical isolate), and their respective ciprofloxacin-resistant mutants, M4/C1,
      M5/C1 and M5/C3, were evaluated. All mutants were stable after one year's storage
      and all grew more slowly in Brain Heart Infusion broth than the parent. The MICs
      of ciprofloxacin, sparfloxacin and tosufloxacin were increased for the mutants of
      M4, whereas the mutants of M5 were less susceptible to ciprofloxacin only. The
      optimal bactericidal concentration (OBC) of each quinolone for all the strains
      was approximately ten-fold greater than the MIC. The OBCs for the mutants were
      increased for ciprofloxacin, but not for the other two quinolones. The DNA
      synthesis IC50 values of all quinolones correlated well with the MIC of each
      drug. All quinolones accumulated rapidly within all five strains; 10 mM magnesium
      chloride decreased the concentration of quinolone accumulated, but carbonyl
      cyanide m-chlorophenyl hydrazone had no effect. Mutant strains M4/C1, M5/C1 and
      M5/C3 accumulated less quinolone than their respective parent strains. DNA
      sequencing of those regions of gyrA and gyrB corresponding to the quinolone
      resistance-determining region in other bacteria did not reveal any differences
      between the parent and mutant strains.

PMID- 9184361
TI  - The effect of quinolones on the intracellular killing of Staphylococcus aureus in
      neutrophil granulocytes.
AB  - The effect of ciprofloxacin, lomefloxacin, fleroxacin and ofloxacin on the
      intracellular killing of Staphylococcus aureus in human neutrophil granulocytes
      was studied. Each drug was tested in concentrations of 0.25, 1, 4, 16 and 64
      times the MIC and the intracellular killing was measured for up to 5 h of
      incubation. All four quinolones increased the intracellular killing in a
      concentration- and time-dependent manner. When compared at concentrations of 4 x
      MIC, ofloxacin increased the killing significantly more than the other
      quinolones. All four quinolones increased the killing significantly more than the
      beta-lactam dicloxacillin. All five antibiotics increased the killing
      significantly relative to the control without antibiotics. None of the
      antibiotics affected the viability of the granulocytes or their ability to
      generate superoxide anion. In conclusion, the quinolones increased the
      intracellular killing of S. aureus in neutrophil granulocytes.

PMID- 9184362
TI  - Delivery of azithromycin to Chlamydia trachomatis-infected polarized human
      endometrial epithelial cells by polymorphonuclear leucocytes.
AB  - An in-vitro model was designed to evaluate whether polymorphonuclear leucocytes
      (PMN) loaded with azithromycin could migrate and deliver the antibiotic in a
      bioactive form to chlamydia inclusions in polarized human endometrial epithelial
      (HEC-1B) cells infected with Chlamydia trachomatis. PMN chemotaxis through the
      extracellular matrix and between infected epithelial cells was readily observed
      if the HEC-1B cells had been infected with chlamydiae for 36 or 48 h. Inclusions
      in infected epithelial cells exposed to PMN loaded with azithromycin were
      initially distinguished by deformed reticulate bodies and an excessive amount of
      chlamydial outer membrane vesicles. As the amount of PMN-delivered antibiotic
      increased, chlamydial inclusions were filled with large cell envelope 'ghosts'
      which were the remnants of lysed reticulate bodies. The lethal effect of
      azithromycin was confirmed by a reduction in the viability of infectious progeny.
      Our results demonstrate that the damage to chlamydiae was due to transport and
      delivery of azithromycin by PMN to infected genital epithelial cells. When
      infected HEC-1B cells were exposed to PMN not loaded with the antibiotic,
      chlamydial morphology was not obviously affected yet few viable progeny could be
      recovered. In this case, PMN-induced damage to host epithelial cells probably
      interrupted chlamydial nutrient acquisition and subsequent maturation and
      formation of infectious progeny.

PMID- 9184363
TI  - A multi-centre study to compare meropenem and cefotaxime and metronidazole in the
      treatment of hospitalized patients with serious infections.
AB  - We conducted a prospective, multi-centre, open, randomized study in 11 UK
      hospitals to compare iv meropenem 1 g tds with the combination of iv cefotaxime 1
      g tds and iv metronidazole 500 mg tds in patients with serious infections. One
      hundred and sixty-one patients were enrolled, of whom 131 were clinically
      evaluable (meropenem, n = 68; cefotaxime/metronidazole, n = 63). The most common
      infections were subsequent to intra-abdominal pathology (meropenem, n = 77%;
      cefotaxime/metronidazole, n = 75%), and were usually accompanied by septicaemia
      (meropenem, n = 61%; cefotaxime/metronidazole, n = 53%). The incidence of a
      satisfactory clinical response was similar in the two groups at the end of
      treatment (93% for meropenem; 92% for cefotaxime/metronidazole) and up to 8 weeks
      later (96% for meropenem; 93% for cefotaxime/metronidazole). Satisfactory
      bacteriological response (success or presumed success) was recorded at the end of
      therapy in 86% of meropenem and 88% of cefotaxime/metronidazole patients. Adverse
      events were reported in 32% of meropenem and 25% of cefotaxime/metronidazole
      patients, and most were mild or moderate and did not require discontinuation of
      therapy. Twenty-one patients (ten meropenem and 11 cefotaxime/metronidazole) died
      during the trial, underlining the severity of the infections being treated in
      this group of patients. None of the deaths was thought to be related to study
      therapy.

PMID- 9184364
TI  - Colorimetric determination of the fluoroquinolones.
AB  - Ciprofloxacin, ofloxacin and norfloxacin formed an amber coloured complex with
      iron(III) nitrate nonahydrate. The complex, which formed instantaneously at room
      temperature, was stable. The solutions of the complex obeyed Beer's law at 370
      nm, the wavelength of maximum absorption of radiation (lambda[max]). The A(1%)
      for norfloxacin, ofloxacin and ciprofloxacin was 202, 207 and 235 respectively.
      The formation of the complex was the basis for the quantitative and qualitative
      determination of the drugs. There was statistically no significant difference (P
      < 0.05) between the results obtained quantitatively by this colorimetric method
      and those obtained by the microbiological assay method.

PMID- 9184365
TI  - Influence of N-acetylcysteine on the formation of biofilm by Staphylococcus
      epidermidis.
AB  - The influence of various concentrations (0.003-8 mg/mL) of N-acetylcysteine on
      the formation of biofilms by 15 strains of Staphylococcus epidermidis has been
      studied. A dose-related decrease in biofilm formation was observed, except with
      the lowest concentrations. The 'slime' index relative to the control was 63%,
      55%, 46%, 34%, 26% and 26% in the presence of 0.25, 0.5, 1, 2, 4, and 8 mg/mL of
      N-acetylcysteine, respectively. These data are statistically significant. The
      inhibitory effect of 2 mg/mL of N-acetylcysteine on slime formation was also
      verified by electron microscopy.

PMID- 9184366
TI  - In-vitro activity of dirithromycin against Chlamydia pneumoniae.
AB  - The in-vitro susceptibilities of 12 strains of Chlamydia pneumoniae were
      determined for dirithromycin, a new macrolide antibiotic, erythromycyclamine, its
      active metabolite, and erythromycin. Both dirithromycin and erythromycyclamine
      had an MIC90 of 2 mg/L, as compared with 0.062 mg/L for erythromycin. The
      combination of dirithromycin and erythromycyclamine appeared to be additive.
      Determination of the role of dirithromycin for the treatment of C. pneumoniae
      infection will depend on the results of prospective, controlled studies utilizing
      culture.

PMID- 9184367
TI  - In-vitro activity of a new oral streptogramin, RPR 106972, alone and in
      combination with rifampicin or ciprofloxacin against Legionella spp.
AB  - The in-vitro activity of RPR 106972, a new oral streptogramin, was compared with
      that of erythromycin, ciprofloxacin, and rifampicin against 45 Legionella spp.
      While rifampicin was the most active of all agents tested, RPR 106972
      demonstrated activity comparable to that of erythromycin and ciprofloxacin.
      Usually, indifference was seen when RPR 106972 was tested in combination with
      rifampicin or ciprofloxacin.

PMID- 9184368
TI  - The use of commercially available lipid emulsions for the preparation of
      amphotericin B-lipid admixtures.
AB  - The use of Intralipid as a dilution medium for Fungizone, previously proposed by
      several groups to reduce the toxicity of amphotericin B, is limited by the
      instability of amphotericin B-lipid admixtures. We have shown that Fungizone
      lipid admixtures with three different lipid emulsions can be stabilized by
      vigorous agitation. Unlike in preparations made by gentle shaking, in stable
      emulsions made by agitation for 18 h, most of the amphotericin B remains
      associated with the lipid phase for at least 1 month at 4 degrees C. The MICs of
      all the admixtures against various Candida spp. were similar to that of Fungizone
      and did not change following storage for at least 2 weeks at 4 degrees C.
      Furthermore, the toxicity of the admixtures, as evaluated by their haemolytic
      activity and amphotericin B-induced K+-leakage from human red blood cells, was
      much lower than that of Fungizone. Hence, amphotericin B-containing lipid
      emulsions made by extended agitation may be advantageous in clinical practice as
      they are efficient, stable, non-toxic and can be easily produced at low cost from
      commercially available ingredients approved for clinical use.

PMID- 9184369
TI  - The effect of ramoplanin coating on colonization by Staphylococcus aureus of
      catheter segments implanted subcutaneously in mice.
AB  - We investigated the effect of ramoplanin coating on Staphylococcus aureus
      colonization of catheter segments in mice. Segments (1 cm in length) were
      inserted subcutaneously, 10(7) cfu of S. aureus were inoculated nearby at
      different times and segments were removed 24 or 48 h later. Uncoated segments
      were colonized with 10(4) to >10(5) cfu, whereas ramoplanin-coated segments had
      mean counts of <10 to approximately 100 cfu. Ramoplanin coating may prevent
      colonization of catheters during the first few days after insertion.

PMID- 9184370
TI  - Accelerated bacteriological evaluation in the management of lower respiratory
      tract infection in general practice.
AB  - This paper examines the use of overnight accelerated bacteriological evaluation
      (ABLE) in the treatment of lower respiratory tract infection in general practice.
      The use of ABLE is compared with the empirical prescribing of antibiotics. The
      results indicate that ABLE leads to a saving in resource use without a
      deterioration in clinical outcome. In view of there being additional benefits,
      such as reduced antibiotic exposure and repeat visits, it is concluded that the
      use of ABLE in the way described would improve the management of lower
      respiratory tract infection in general practice.

PMID- 9184371
TI  - Carbapenems in febrile neutropenic patients.

PMID- 9184372
TI  - Are TEM beta-lactamases encoded by pBR322 and Bluescript plasmids enzymatically
      indistinguishable?

PMID- 9184373
TI  - In-vitro activity of ketolides against mycoplasmas.

PMID- 9184374
TI  - Susceptibility of multi-resistant Streptococcus pneumoniae to ciprofloxacin,
      ofloxacin and levofloxacin.

PMID- 9184375
TI  - Cancer immunology.

PMID- 9184376
TI  - Identification of a Kb-restricted CTL epitope of beta-galactosidase: potential
      use in development of immunization protocols for "self" antigens.
AB  - The use of recombinant and synthetic vaccines in the treatment of cancer has
      recently been explored using model tumor associated antigens (TAA), many of which
      do not model the immunological state of affairs in which the TAA is expressed by
      normal tissues. One potentially useful model Ag is beta-galactosidase (beta-gal).
      Because the activity of this enzyme is so easily detectable, this gene has been
      inserted into a large number of recombinant viruses and tumors useful to the
      cancer vaccinologist. In addition, numerous transgenic mouse colonies that have
      tissue-specific expression of beta-gal have been developed, enabling the modeling
      of tolerance to "self" Ags. Since most of these mice have an H-2b background, we
      generated cytotoxic T lymphocytes (CTL) capable of recognizing beta-gal
      expressing tumor cells of C57BL?6 origin and have determined that their
      restriction element is the K(b) molecule. Using an allele-specific epitope
      forecast to generate a panel of candidate peptides, we have determined that the
      K(b)-restricted sequence is DAPIYTNV and corresponds to amino acids 96-103 of the
      intact beta-gal molecule. A recombinant vaccinia virus (rVV-ES beta-gal96-103)
      was constructed that encoded the peptide epitope preceded by an endoplasmic
      reticulum insertion signal sequence. Tumor cells infected with this rVV were
      recognized by the original CTL that had been used to identify the epitope.
      Furthermore, splenocytes of mice immunized with a rVV encoding the full-length
      beta-gal molecule and restimulated with the DAPIYTNV peptide specifically
      recognized tumor cells expressing beta-gal. The identification of this
      immunogenic beta-gal sequence enables the modeling of immunization strategies in
      animal models of malignant disease in which the target antigen is a "self"
      protein.

PMID- 9184377
TI  - Identification of genes coding for tumor antigens recognized by cytolytic T
      lymphocytes.
AB  - Strategies have been developed to characterize tumor antigens recognized by
      cytolytic T lymphocytes (CTL). We use a genetic approach based on the
      transfection of HLA genes and cDNA libraries in COS cells to isolate the gene
      producing the antigenic peptide. The tumor-specific expression of this gene can
      be evaluated by cDNA synthesis and quantitative PCR amplification. Transfection
      of fragments of the isolated gene allows the identification of the region
      encoding the antigenic peptide. Peptides are synthesized and tested for their
      ability to sensitize target cells to lysis by the CTL.

PMID- 9184378
TI  - Considerations for the clinical development of cytokine gene-transduced tumor
      cell vaccines.
AB  - In preclinical models, tumor cells genetically altered to secrete cytokines or
      express costimulatory molecules can generate systemic antitumor immunity. In some
      studies, these tumor vaccines have been shown to eradicate micrometastases. These
      results have led to the initiation of numerous phase I clinical trials employing
      either genetically modified or allogenic tumor vaccines. This article addresses a
      number of issues related to the clinical development of cytokine gene-transduced
      tumor cell vaccines including: (1) the production of cytokine-secreting tumor
      vaccines; and (2) the preclinical feasibility and toxicity studies required for
      testing these vaccines in patients with cancer.

PMID- 9184379
TI  - Stimulation of tumor-specific immunity using tumor cell plasma membrane antigen.
AB  - Plasma membranes isolated from tumor cells retain biologically active class I MHC
      proteins on their surfaces. CD8+ T-cell activation by membrane antigen is much
      more effective when the small membrane vesicles (<1-microm diameter) are
      displayed on a surface with dimensions approaching those of a cell (5-microm
      diameter). Previous work had shown that tumor membrane antigen incorporated onto
      silica microspheres could augment tumor-specific CTL responses in vivo and
      significantly reduce syngeneic tumor growth. Antigen on cell-sized solid supports
      has been termed large multivalent immunogen (LMI). Methods are described for
      preparing LMI using either silica or latex microspheres. LMI made using either
      are active in vivo in reducing tumor growth, suggesting that the nature of the
      support is not critical as long as it is of the appropriate dimensions and has a
      surface that allows adsorption of the membrane vesicles. Latex microspheres
      provide some advantages over the previously described silica microspheres with
      respect to handling and characterization. The effects of LMI on in vivo CTL
      activation and tumor growth suggest that this approach may have potential for
      application to clinical immunotherapy of cancers.

PMID- 9184380
TI  - Purification of heat shock protein-peptide complexes for use in vaccination
      against cancers and intracellular pathogens.
AB  - This article describes the methods used for the purification of heat shock
      proteins gp96, hsp90, and hsp70 from murine and human tissues and cell lines. The
      heat shock proteins purified by the methods described are associated
      noncovalently with an array of cellular peptides. The use of heat shock protein
      peptide complexes for eliciting prophylactic and therapeutic immunity to cancers
      and infectious diseases is discussed.

PMID- 9184381
TI  - Study of immune response to tumors in the rat.
AB  - Use of the rat as host for the study of cancer has become popular for several
      reasons. The larger body size compared to mice is especially convenient for lines
      of experiments involving surgical manipulation, transplantation, or biochemical
      purification of molecules of interest. Immune response to cancer is also studied
      in rat models, and this article focuses on the methodological aspects of in vivo
      and in vitro protocols related to rat tumor immunology.

PMID- 9184383
TI  - Comparative effects of recombinant staphylokinase and streptokinase on platelet
      aggregation.
AB  - Recombinant staphylokinase (RSTA) has been shown to offer promise as a
      thrombolytic agent. In contrast to streptokinase (SK), few studies have been
      devoted to possible effects of RSTA on platelets. We have compared the capacity
      of RSTA and SK to trigger platelet aggregation and to modify ADP (2.5 microM)
      response in platelet-rich plasma (PRP) of 125 healthy subjects. Thus, exposure of
      PRP to SK (40 to 50 micrograms/ml) induced platelet aggregation in 6 out of 25
      subjects. However, under the same conditions, RSTA failed to induce platelet
      aggregation in all cases (25 out of 25 subjects). In contrast to RSTA, SK (0.4 to
      50 micrograms/ml) greatly reduced ADP-induced platelet aggregation in 12 out of
      25 subjects. Preincubation of plasma with SK is associated with a decrease in the
      fibrinogen concentration. Furthermore, there was a good correlation between SK
      induced fibrinogenolysis and SK-induced platelet aggregation defect (r2 = 0.9; p
      = 0.001). No fibrinogenolysis was observed when different amounts of RSTA (0.4 to
      50 micrograms/ml) were incubated in plasma for one min. However, there was a
      marked decrease in fibrinogen level (about 50%) when the plasma was incubated for
      five min with a very high concentration of RSTA. SK markedly enhanced the
      platelet response to ADP in 13 out of 25 subjects. In PRP of 6 out of 25
      subjects, SK induces platelet aggregation and potentiates platelet response to
      ADP, however in PRP of 7 out of 25 subjects, SK caused only the increase of
      platelet response to ADP. The monoclonal antibody anti-Fc gamma RIIa1, I-3 (2
      micrograms/ml), abolished SK-induced platelet aggregation and SK-enhanced ADP
      induced platelet aggregation. In all cases (25 out of 25 subjects), RSTA failed
      to potentiate platelet response to ADP. These findings confirm that RSTA has a
      lesser fibrinogenolytic ability than SK and suggest its negligible effect on
      platelet function.

PMID- 9184382
TI  - Serum thrombopoietin level is not regulated by transcription but by the total
      counts of both megakaryocytes and platelets during thrombocytopenia and
      thrombocytosis.
AB  - Thrombopoietin (Tpo) regulates platelet production, but the mechanisms regulating
      the serum Tpo level and platelet count in circulation have been a subject of
      debate. Tpo was reported to be expressed mainly in liver and kidney, but we found
      that Tpo is expressed in all tissues examined: abundantly in liver, kidney,
      muscle, colon, brain and intestine, and moderately in bone marrow, spleen, lung,
      stomach, heart, thymus, ovary, and endothelial and leukemic cell lines. The
      levels of Tpo transcripts in major Tpo producing organs, liver and kidney, and in
      the platelet production sites bone marrow and spleen, were constant during acute
      thrombocytopenia induced by anti-platelet monoclonal antibody administration in
      mice, and during thrombocytosis induced by Tpo injection. Furthermore, we noticed
      that platelet count is not exactly inversely proportional to serum Tpo level.
      During acute thrombocytopenia, serum Tpo level transiently increased a few hours
      after antibody injection, and returned to the basal level just when matured
      megakaryocytes accumulated in bone marrow and spleen but the platelet count was
      still low. Matured megakaryocytes in bone marrow and spleen increased when the
      serum Tpo level decreased, and decreased when platelet count rebounded. Taken
      together with other observations, we propose here a modified version of Kuter and
      Rosenberg's theory, that is, Tpo is constitutively expressed in a variety of
      organs throughout the body, even in acute thrombocytopenia and thrombocytosis,
      and that the serum Tpo level is not regulated by Tpo gene expression nor only by
      platelet counts in circulation, but by the total counts of both megakaryocytes in
      bone marrow and spleen and of platelets in circulation.

PMID- 9184384
TI  - The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a
      risk factor for arterial disease and venous thrombosis.
AB  - Mild hyperhomocysteinemia has been identified as a risk factor for arterial
      disease and for venous thrombosis. Individuals homozygous for the thermolabile
      variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results
      from a common mutation Ala677-->Val and is found in 5-15% of the general
      population, have significantly elevated plasma homocysteine levels and may
      account for one of the genetic risk factors in vascular disease. We have analyzed
      the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous
      thrombosis. We studied 191 patients with arterial disease and 127 individuals
      with venous thrombosis and compared with 296 unmatched controls. The results
      showed that there was a high prevalence of homozygotes for the mutated MTHFR-T
      allele among a group of patients with arterial disease (19%) in the absence of
      hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to
      controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of
      homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93
      (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio
      of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g.
      factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S,
      antithrombin III, or factor XII) from the 127 overall cases with venous
      thrombosis. These data support the hypothesis that being a homozygote for the
      MTHFR-T is a risk factor for the development of arterial disease and also for
      venous thrombosis.

PMID- 9184385
TI  - Factor V Leiden is associated with repeated and recurrent unexplained fetal
      losses.
AB  - Activated protein C resistance (APCR) is responsible for most cases of familial
      thrombosis. The factor V missense mutation Arg506 > Gln (FV Leiden) has been
      recognized as the commonest cause of this condition. Recently, it has been
      suggested that APCR is associated with second trimester fetal loss. We
      investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian
      women with a history of two or more unexplained fetal losses. A group (n = 118)
      of parous women with uneventful pregnancies from the same ethnical background
      served as control. We found the mutation in 7 cases (16.28%) and 5 controls
      (4.24%; p = 0.011). A statistically significant difference between women with
      only early fetal loss vs those with late events (p = 0.04) was observed. Our data
      demonstrate a strong association between FV Leiden and fetal loss. Furthermore,
      they indicate that late events are more common in these patients.

PMID- 9184386
TI  - High prevalence of elevated factor VIII levels in patients referred for
      thrombophilia screening: role of increased synthesis and relationship to the
      acute phase reaction.
AB  - A recent report from the Leiden Thrombophilia Survey identified high factor VIII
      activity levels as an independent risk factor for venous thromboembolism in a
      population survey. As the study measure for factor VIII was a one-stage
      coagulation assay, and since markers for the acute phase reaction were not
      assessed, it remained uncertain whether the increase was due to a constitutional
      increased rate of synthesis, to circulating activated factor VIII, or to an acute
      phase response. We added factor VIII activity assay (FVIII:C), factor VIII
      antigen (FVIII:Ag), vWF antigen (vWF:Ag), ABO blood group, fibrinogen and C
      reactive protein to our routine thrombophilia screen of patients referred because
      of unexplained thromboembolism. Elevated FVIII:C (> 1.5 iu/ml) emerged as the
      single commonest abnormality detected in 25.4% of a group of 260 such patients.
      FVIII:C and FVIII:Ag were highly correlated (p = 0.003), showing that this
      represented a true increase in FVIII. In 4 of 46 patients this was clearly
      attributable to an acute phase reaction. Eleven others showed minor elevation of
      ESR and one of CRP. Neither FVIII:C or FVIII:Ag showed significant correlation
      with fibrinogen, ESR or C-reactive protein by non parametric analysis. Although
      there was an excess of patients with B blood group (known to be associated with
      FVIII:C levels which are approximately 15% higher than those in blood group O),
      this could not account for the marked elevation of factor VIII observed in these
      patients. We conclude that factor VIII activity assay should be a routine part of
      thrombophilia screening. We are investigating the cause of the increased
      synthesis, initially by means of family studies and linkage analysis with
      polymorphic markers of the FVIII locus. We postulate that it may be constitutive
      in some cases and in others an abnormal or exaggerated response to inflammatory
      stimuli.

PMID- 9184387
TI  - Prothrombin fragment F1+2 is not predictive for recurrent venous thromboembolism.
AB  - It would be important to estimate in advance the risk of recurrent thrombosis.
      Deficiencies of antithrombin, protein C or protein S, or resistance to activated
      protein C are associated with a biochemically detectable prethrombotic state. It
      is thus far unknown whether in patients with a history of thromboembolism but
      without a defined clotting abnormality a heightened coagulation activation is
      detectable. We investigated the value of prothrombin fragment F1+2 (F1+2) as a
      predictor of recurrent venous thromboembolism. Furthermore, we compared the F1+2
      levels of thrombosis patients without a defined clotting defect to those of
      Factor V Leiden patients with a history of venous thrombosis and to those of
      healthy controls. 180 patients without a defined clotting abnormality and 73
      patients with Factor V Leiden were prospectively followed after discontinuation
      of oral anticoagulants for venous thrombosis and F1+2 was measured at regular
      intervals. Recurrent venous thromboembolism occurred in 23 (9%) of the 253
      patients. Before or at several time points after oral anticoagulants, no
      significant difference in F1+2 levels was found in patients with and without
      recurrent thrombosis. F1+2 levels at 3 weeks and prior to recurrence were not
      significantly different in both patient groups. Over a one-year observation
      period, F1+2 levels of both patients with and without Factor V Leiden were higher
      than those of the controls. No difference in F1+2 was seen between patients with
      and without Factor V Leiden. We conclude that monitoring of F1+2 is not suitable
      for identification of individuals at risk of recurrent venous thrombosis.
      Permanent hemostatic system activation is detectable both in patients with a
      defined abnormality of the clotting system and in patients in whom a particular
      defect has not (yet) been identified.

PMID- 9184388
TI  - Subcutaneous recombinant hirudin (HBW 023) versus intravenous sodium heparin in
      treatment of established acute deep vein thrombosis of the legs: a multicentre
      prospective dose-ranging randomized trial. International Multicentre Hirudin
      Study Group.
AB  - The aim of this multicentre, prospective, randomised, dose-ranging study was to
      compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023)
      against intravenous sodium heparin in acute lower limb deep venous thrombosis
      (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5
      +/- 1 days. HBW 023 was given according to body-weight in three dose groups.
      Thromboembolic disease was assessed by phlebography and ventilation/perfusion
      (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were
      enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer
      patients on HBW 023 developed new V/Q abnormalities during the treatment period,
      (p = 0.006). There was no difference between the groups in thrombus extension or
      regression, major bleeding complications or serious adverse events. There were
      significantly fewer findings of new V/Q mismatch after treatment with HBW 023,
      and anticoagulant control was superior in these patients.

PMID- 9184389
TI  - A comparison of a moderate with moderate-high intensity oral anticoagulant
      treatment in patients with mechanical heart valve prostheses.
AB  - BACKGROUND: The long-term administration of oral anticoagulants to patients with
      mechanical heart valve prostheses is generally accepted. However, the appropriate
      intensity of oral anticoagulant treatment in these patients is still
      controversial. METHODS AND RESULTS: From March 1991 to March 1994, patients
      referred to the Padova Thrombosis Center who had undergone mechanical heart valve
      substitution at least 6 months earlier were randomly assigned to receive oral
      anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity
      (target INR = 4). Principal end points were major bleeding, thromboembolism and
      vascular death. Minor bleeding was a secondary end-point. A total of 104 patients
      were assigned to the target 3 group and 101 to the target 4 group; they were
      followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points
      occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20
      patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic
      events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient
      years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The
      12 recorded episodes of thromboembolism, 4 of which consisted of a visual
      deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per
      100 patient-years) and 6 in the target 4 group (2.1 per 100 patient-years). There
      were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target
      3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times
      (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100
      patient-years) in the target 4 group (p = 0.001). CONCLUSIONS: Mechanical heart
      valve patients on anticoagulant treatment who had been operated on at least 6
      months earlier experienced fewer bleeding complications when maintained on a
      moderate intensity regimen (target INR = 3) than those on a moderate-high
      intensity regimen (target INR = 4). The number of thromboembolic events and
      vascular deaths did not differ between the two groups.

PMID- 9184390
TI  - Effect of fixed minidose warfarin, conventional dose warfarin and aspirin on INR
      and prothrombin fragment 1 + 2 in patients with atrial fibrillation.
AB  - The efficacy of conventional dose adjusted oral anticoagulation for stroke
      prevention in patients with non-valvular atrial fibrillation is well-documented
      but not considered ideal as primary antithrombotic treatment in elderly patients.
      The antithrombotic effect of fixed minidose warfarin 1.25 mg/day alone or in
      combination with aspirin 300 mg/day, of conventional dose adjusted warfarin (INR
      2.0-3.0), and of aspirin 300 mg/day have been investigated in outpatients with
      chronic nonvalvular atrial fibrillation in the second Copenhagen Atrial
      Fibrillation, Aspirin and Anticoagulant Therapy Study (AFASAK 2). In order to
      investigate the effect on the coagulation system of the treatments, the
      International Normalized Ratio of the prothrombin time (INR) and prothrombin
      fragment 1 + 2 (F1 + 2) were monitored at baseline and after three months of
      treatment in 100 patients consecutively included in the trial. At baseline no
      differences in INR and F1 + 2 between the four treatment groups were present.
      After three months of therapy the level of INR increased significantly from
      baseline in patients receiving warfarin in any dose and the level of F1 + 2
      decreased significantly by combined minidose warfarin-aspirin and by dose
      adjusted warfarin. When comparing the changes over time in F1 + 2 (three-month
      value minus baseline value) during therapy with fixed minidose warfarin, combined
      minidose warfarin-aspirin and aspirin alone no significant difference between the
      groups was found. In conclusion, INR was changed by all three warfarin regimens
      but only dose adjusted warfarin (INR 2.0-3.0) had a marked effect on F1 + 2.

PMID- 9184391
TI  - Defective interaction between von Willebrand factor and platelet glycoprotein Ib-
      a familial study of peripheral arterial occlusive disease.
AB  - Hemostatic variables and platelet function were assessed as a part of a genetic
      study in 15 patients with symptomatic peripheral arterial occlusive disease
      (PAOD) and 15 healthy siblings from ten families. D-dimer, a degradation product
      of cross-linked fibrin, was increased in the PAOD group (mean +/- SD) (448 +/-
      177 vs. 333 +/- 121 ng/ml, p < 0.05). Ristocetin-induced maximal platelet
      aggregation (RIPA) was reduced in the PAOD group in response to both a higher
      (0.75 mg/ml) (67 +/- 28 vs. 87 +/- 14%, p = 0.02) and a lower (0.55 or 0.60
      mg/ml) (33 +/- 21 vs. 59 +/- 32%, p = 0.02) concentration of ristocetin.
      Accordingly, the rate of primary aggregation was smaller, and a larger threshold
      concentration of ristocetin was needed to cause aggregation. However, ristocetin
      cofactor activity, von Willebrand factor (vWF) antigen and its multimer
      distribution, plasma glycocalicin, platelet glycoprotein Ib content and the
      binding of vWF to frozen and thawed washed platelets were equal in both groups.
      Thus, the observed reduced RIPA in patients with PAOD is less likely to reflect a
      down-regulation or blunted binding affinity in the platelet surface glycoprotein
      Ib.

PMID- 9184393
TI  - Factor VIII Ise (R2159C) in a patient with mild hemophilia A, an abnormal factor
      VIII with retention of function but modification of C2 epitopes.
AB  - We found a patient with mild hemophilia A who had no detectable factor VIII
      antigen (FVIII:Ag), as shown by two-site ELISA using inhibitor alloantibodies
      (TK). We then analyzed A2, A2/B, and C2 antigen of the patient's DDAVP-induced
      FVIII using several anti-FVIII monoclonal antibodies. Factor VIII activity
      (FVIII:C) was increased from 12 to 42 U/dl by the administration of DDAVP. The
      DDAVP-induced increases in the A2 and A2/B antigens were 40 and 36 U/dl,
      respectively. However, the increase in the C2 antigen was only 7.5 U/dl. SSCP
      analysis and subsequent sequencing demonstrated an Arg to Cys transition at codon
      2159. The anti-FVIII:C titer of monoclonal antibody, NMC-VIII/5 which recognized
      the C2 domain, against normal plasma was 450 Bethesda U/mg of IgG. However, the
      titer against DDAVP-treated patient's plasma was only 15 Bethesda U/mg. We also
      tested DDAVP-induced increase in the FVIII:Ag in another mild hemophilia A
      patient with the same mutation at Arg2159. Increase in his C2 antigen levels was
      only 19% of those in the A2 and A2/B antigen. We designate this abnormal FVIII as
      FVIII Ise. Our results show that a missense mutation at Arg2159 to Cys modifies
      the antigenicity of the C2 domain.

PMID- 9184392
TI  - Autoantibodies to phospholipids and to the coagulation proteins in AIDS.
AB  - In HIV-1 infection, an increased prevalence of anticardiolipin autoantibodies
      (aCL) and lupus anticoagulant (LA) has been described. In order to see if these
      antibodies are isolated or, like in autoimmune diseases, associated with
      hematological disorders and with antibodies to other phospholipids and to
      proteins of coagulation, we investigated 3 groups of patients: 1. 342 HIV-1
      infected patients, 2. 145 control patients including 61 systemic lupus
      erythematosus (SLE) patients, 58 patients with a connective tissue disease, 15
      patients with stroke, 11 patients with syphilis and 3. 100 blood donors. In HIV-1
      infection antiprothrombin (aPrT) antibodies were present in 2% of patients, the
      prevalence of antiphosphatidylcholine antibodies (aPC) (50%) was almost as high
      as aCL (64%), and 39% had both antibodies. Absorption on liposomes of the latter
      revealed an heterogeneous mixture of aCL and aPC or cross-reacting antibodies. In
      contrast with SLE, anti-beta 2-glycoprotein I (4%), LA (1%), biological false
      positive test for syphilis (0.3%), thrombosis (p < 0.001) were uncommon. In HIV-1
      infection, antiphospholipid antibodies do not associated with features linked to
      them in SLE or syphilis.

PMID- 9184394
TI  - Hepatitis G viral RNA in serum and in peripheral blood mononuclear cells and its
      relation to HCV-RNA in patients with clotting disorders.
AB  - The hepatitis G virus (HGV) has recently been identified as a new member of the
      Flaviviridae family. Infection by this virus is thought to be associated with
      blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum
      or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133
      patients) was investigated in patients with clotting disorders using a sensitive
      reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in
      serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA
      was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of
      the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus
      (HCV), especially with HCV genotype 1b, the most common genotype in Belgium. Of
      these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two
      patients who were solely infected with HGV had normal serum ALT.HGV-RNA in PBMC
      was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case
      of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment.
      Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation
      of treatment. In one patient, persistent serum ALT elevation seems to be
      associated with continued HGV viremia, despite the disappearance of serum HCV
      RNA.

PMID- 9184395
TI  - Location on the human genetic linkage map of 26 genes involved in blood
      coagulation.
AB  - Several human genetic linkage maps have been constructed as part of the Human
      Genome Project. These maps show the positional order of closely linked, highly
      informative AC-repeat polymorphisms on each human chromosome, and are extremely
      useful in genetic linkage analysis of inheritable diseases. For a candidate gene
      approach the current linkage maps are less useful, since they consist mainly of
      anonymous markers rather than of specific genes. This situation also applies for
      inheritable disorders of blood coagulation. Numerous genes are involved in the
      blood coagulation cascade and its regulation, and can be considered as candidate
      genes for unexplained haemophilia and thrombophilia. We have selected 29
      candidate genes that seem to be the ones most likely to be involved in
      thrombophilia. For 19 genes genotype data were already present in the CEPH
      database (version 7.0). We typed 7 additional genes in the CEPH reference
      families, i.e. the factor V, factor XII, protein C, protein S, prothrombin,
      thrombomodulin, and heparin cofactor II gene. The genotype data were used to
      integrate these 26 genes in the current genetic linkage map, and to identify
      closely linked AC-repeat polymorphisms. This information will benefit the
      investigation of inheritable disorders of blood coagulation, especially
      thrombophilia.

PMID- 9184396
TI  - Fibrinogen heterogeneity in homozygous plasminogen deficiency type I: further
      evidence that plasmin is not involved in formation of LMW- and LMW'-fibrinogen.
AB  - Human plasma fibrinogen is heterogeneous in SDS-polyacrylamide gel
      electrophoresis and other methods for separation of proteins by molecular size. A
      high molecular weight fraction (HMW-fibrinogen, 340 kD) contributes approximately
      50% of total fibrinogen antigen. Low molecular weight fibrinogen (LMW-fibrinogen,
      300 kD) adds another 40%. The residual amount is LMW'-fibrinogen with a molecular
      weight of 280 kD, and a small amount of very high molecular weight fibrinogen
      (Fib420), the product of alternative splicing of the A alpha-chain genetic
      information, resulting in an extended A alpha-chain C-terminus. Fibrinogen was
      detected by specific immunostaining of nonreduced SDS-PAGE gel immunoblots with
      antibodies against fibrinopeptide A. Using densitometric scans of the immunoblots
      we found a ratio of HMW-, LMW- and LMW'-fibrinogen in a patient with homozygous
      plasminogen deficiency that was similar to the ratio found in immunoblots of
      plasma from healthy blood donors. Treatment with plasminogen concentrate resulted
      in a slight decrease of the proportion of HMW-fibrinogen, followed by an increase
      to 78%. The LMW'-fibrinogen band gained intensity initially, increasing to 11.9%
      of fibrinogen antigen 6 h after starting plasminogen infusion, but then dropped
      to levels below detection limit of the immunoblotting assay. LMW-fibrinogen
      remained constant during the initial 72 h of plasminogen treatment, then dropping
      to values in the range of 22-25% afterwards. The proportion of HMW-, LMW-, and
      LMW'-fibrinogen again reached the initial levels two weeks after starting
      treatment with plasminogen concentrate. We conclude that plasminogen is not
      involved in the limited proteolysis leading to formation of LMW-fibrinogen and
      LMW'-fibrinogen in the absence of a generalized fibrinolytic condition.
      Fibrinolytic activation may lead to the formation of fibrinogen degradation
      product X, which appears in a similar position as LMW'-fibrinogen in SDS-PAGE.

PMID- 9184397
TI  - Variation in plasma fibrinogen over one year: relationships with genetic
      polymorphisms and non-genetic factors.
AB  - We analyzed plasma fibrinogen level in relation to genetic polymorphisms in the
      alpha- and beta-fibrinogen gene loci. Furthermore, the association of other CVD
      risk markers with fibrinogen was studied twice, with a time interval of one year
      in 50 to 60 year old men (n = 183). DNA polymorphisms were detected by PCR and
      digestion with Taq I (alpha-fibrinogen), Hind III and Bcl I (beta-fibrinogen)
      restriction enzymes. The correlation coefficient between fibrinogen measurements
      was 0.48 (p < 0.001). Blood leucocytes and waist-to-hip circumference ratio were
      the strongest correlates of fibrinogen level in both examinations, and the
      changes in leucocyte count and plasma fibrinogen correlated positively (r = 0.40,
      p < 0.001). In Eastern Finnish men, the Taq I, Hind III or Bcl I restriction
      fragment length polymorphisms of the alpha- or beta-fibrinogen gene loci did not
      associate with fibrinogen level, either cross-sectionally or longitudinally.

PMID- 9184398
TI  - Factor VII and fibrinogen levels examined by age, sex, and other atherosclerotic
      risk factors in a Japanese population. The Jichi Medical School Cohort Study.
AB  - Factor VII coagulant activity (FVIIc) and fibrinogen (Fbg) levels have been
      investigated as cardiovascular risk factors. We studied these two factors with
      stratification for age, sex and blood pressure, and the relation with other
      atherosclerotic risk factors in a Japanese general population. The subjects were
      3,139 Japanese (1,315 males and 1,824 females) aged 30 to 89 in 1992 and 1993. A
      linear increase with age was observed in the levels of Fbg in both men and women,
      but no differences were observed between men and women in each age group. A
      linear increase with age was also seen in the levels of FVIIc in women, but the
      levels of FVIIc in men were significantly higher for the age group 40-49 years
      than for any other age group. The levels of FVIIc in women were significantly
      higher than in men at age > or = 60 years. As concerning the effect of alcohol
      intake status, Fbg had a tendency to decrease with alcohol intake. Fbg and FVIIc
      levels were associated with an increase in smoking status in men, but no
      association was seen in women in either Fbg or FVIIc. FVIIc was positively
      correlated with age, body mass index, total cholesterol, triglycerides and
      fasting insulin level. Fbg was positively correlated with age, systolic blood
      pressure, diastolic blood pressure, total cholesterol, LDL-cholesterol and
      triglycerides in women, but Fbg had few positive correlations with risk factors
      in men. A comparison with previous Western studies showed that the Fbg levels of
      our Japanese population were lower than those of the Caucasians studied, but the
      present FVIIc levels were nearly the same level or slightly higher than theirs.
      The association of Fbg and FVIIc and with other cardiovascular risk factors in
      Japanese was similar to those observed in Caucasians.

PMID- 9184399
TI  - CD11b/CD18 mediates the neutrophil chemotactic activity of fibrin degradation
      product D domain.
AB  - Coagulation and fibrinolysis universally accompany tissue injury and repair. The
      accumulation of regionally generated fibrin degradation products (FDP) may modify
      the local inflammatory response. We have found FDP to be potent neutrophil
      chemotaxins. We separated plasmin FDP by chromatofocusing and found chemotactic
      activity limited to fractions containing the fibrinogen D domain (D-D dimer and D
      monomer). The bioactivity of the D-D dimer did not require an intact cross link
      site as removal of this sequence with puff adder venom or hypocalcemic plasmic
      digestion did not decrease chemotaxis. Peptide inhibition studies confirmed that
      the chemotactic region did not involve terminal gamma chain sequences or alpha
      chain RGD motifs. The internal gamma chain peptide KYGWTVFQKRLDGSV (P1), known to
      bind CD11b/CD18, exhibited concentration dependent chemotactic activity.
      Similarly, monoclonal antibodies directed against CD11b/CD18 blocked PMN
      migration to FDP without similar inhibition of chemotaxis to IL-8 or LTB4. Thus,
      neutrophil chemotaxis to FDP is mediated by interactions between the fibrinogen D
      domain and CD11b/CD18.

PMID- 9184400
TI  - Prediction of changes in levels of haemostatic variables during natural menstrual
      cycle and ovarian hyperstimulation.
AB  - To find if there is a relation between levels of haemostatic variables at low and
      high hormonal levels (oestradiol and progesterone) in an individual, blood
      samples were drawn from 12 women repeatedly during one menstrual cycle (Study I)
      and from 14 women undergoing in vitro fertilization, before hormonal stimulation
      and daily during the periovulatory period (Study II). Regression coefficients
      were calculated between minimum (independent) and maximum (dependent) values in
      both studies. In Study II highly significant regression coefficients were found
      between oestradiol minimum (pretreatment) and maximum (median 105 and 4730
      pmol/l, respectively) for coagulation factors FVIII, von Willebrand Factor
      (antigen), FVII (activity and antigen), fibrinogen, protein C, protein S (free),
      antithrombin, plasminogen and plasminogen activator inhibitor-1; furthermore,
      between progesterone-minimum at day -3 or -2 (related to ovum pick up) and
      maximum (median 4.7 and 98 nmol/l, respectively) for FVIII, von Willebrand
      Factor, FVII (activity and antigen), protein C, protein S (free), and
      plasminogen. In Study I, where much lower hormonal levels were obtained at
      maximum (oestradiol median 297 pmol/l and progesterone 47 nmol/l), the same
      pattern was observed especially for FVII, FX, fibrinogen, plasminogen and plasmin
      inhibitor. Thus, the concentration of a haemostatic variable at a low oestradiol
      or progesterone level can predict the level at a high hormonal level.

PMID- 9184401
TI  - The coagulation and fibrinolytic responses of baboons after in vivo thrombin
      generation--effect of interleukin 6.
AB  - Disseminated intravascular coagulation (DIC) may lead to severe thrombotic or
      hemorrhagic complications. The present work was undertaken to study the effect of
      interleukin 6 (IL-6) on variations of key coagulation and fibrinolytic parameters
      in plasma in a baboon model of experimental DIC induced by injection of factor Xa
      and phospholipids at dosages leading to partial (48%) or complete fibrinogen
      depletion. Transient increases of D-dimer, fibrinopeptide A, thrombin
      antithrombin and the activated partial thromboplastin time were observed. Each
      parameter had a particular (time and Xa/phospholipid dose dependent) pattern of
      changes. The principal effect of IL-6 was a more rapid restoration of fibrinogen
      concentrations and of overall coagulation tests. Injection of factor
      Xa/phospholipids led also to a rapid increase of tissue-type plasminogen
      activator (t-PA) the extent of which was dependent on Xa/phospholipid dose.
      Pretreatment with IL-6 induced a threefold increase of basal t-PA and a
      corresponding increase of the t-PA response. Plasminogen activator inhibitor type
      1 (PAI-1) concentrations did not change after low dose Xa/phospholipids, but
      increased eightfold after high dose Xa/phospholipids, IL-6 pretreatment induced
      within 8 h a twentyfold increase of PAI-1 but no further increase was observed
      after injection of factor Xa/phospholipids. Thus, in vivo thrombin generation
      leads to dynamic modifications of the coagulation and fibrinolytic systems. The
      principal effect of IL-6 is a more rapid normalization of overall coagulation
      tests, due to normalization of fibrinogen, and an increased t-PA release response
      which is partially counteracted by increased PAI-1 concentrations.

PMID- 9184402
TI  - Pharmacodynamic and safety results of PEG-Hirudin in healthy volunteers.
AB  - PEG-Hirudin, a chemically defined conjugate of recombinant hirudin and two
      molecules of polyethylene glycol (PEG)-5000 is a highly selective direct thrombin
      inhibitor with a significantly longer duration of action than non-conjugated
      recombinant hirudin permitting once daily subcutaneous administration. A series
      of placebo-controlled, randomized, Phase I clinical trials were conducted in 75
      healthy volunteers to investigate the anticoagulant effects, safety and
      pharmacodynamics of PEG-Hirudin when administered intravenously as a bolus
      injection, infusion, and subcutaneously. After single i.v. injections of various
      doses of PEG-Hirudin (0.03-0.3 mg/kg) dose-dependent increases in anti-IIa
      activity and APTT were observed. Four hours after injection of 0.3 mg/kg, mean
      plasma concentration expressed in terms of anti-IIa activity was still 0.89
      micrograms/ml, corresponding to a 1.8-fold prolongation of APTT. Continuous
      intravenous infusions of 0.01 and 0.02 mg/kg/h PEG-Hirudin resulted in maximum
      anti-IIa activities of 0.42 micrograms/ml and 0.77 micrograms/ml, respectively,
      at the end of a six-hour infusion period without having reached steady state at
      this time. After termination of the infusion, anticoagulant activity displayed an
      immediate exponential decrease. The anticoagulant activities of single
      subcutaneous doses of 0.05 to 0.6 mg/kg were studied in a further series of
      investigations and slow increases and prolonged durations of anti-IIa activity
      and APTT prolongation were found. Repeated, once daily subcutaneous
      administrations of 0.2 to 0.4 mg/kg for five days resulted in dose-dependent
      prolongations of APTT and increases in anti-IIa activity without completely
      reaching steady state conditions. In a further study, 0.3 mg/kg of PEG-Hirudin
      was given as an i.v. bolus injection followed by three repeated single daily s.c.
      injections. In this trial, the APTT was shorter than expected from previous
      studies; therefore, a direct comparison of various APTT reagents was made in the
      intravenous infusion trial. Of the APTT reagents tested, BioMerieux Silimat and
      IL-ellagic acid proved to be the most sensitive to PEG-Hirudin. The hirudin
      derivative PEG-Hirudin was tolerated very well without immuno-allergic side
      effects. In view of the significantly prolonged anticoagulant efficacy in
      comparison to non-conjugated r-hirudin, PEG-Hirudin is a promising compound
      especially for repeated once daily subcutaneous administration.

PMID- 9184403
TI  - Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass--assessment
      of the whole blood ecarin clotting time.
AB  - The use of recombinant (r) hirudin as an anticoagulant in performing
      extracorporeal circulation systems including cardiopulmonary bypass (CPB) devices
      requires a specific and easy to handle monitoring system. The usefulness of the
      celite-induced activated clotting time (ACT) and the activated partial
      thromboplastin time (APTT) for r-hirudin monitoring has been tested on ex vivo
      blood samples obtained from eight patients treated with r-hirudin during open
      heart surgery. The very poor relationship between the prolongation of the ACT and
      APTT values and the concentration of r-hirudin as measured using a chromogenic
      factor IIa assay indicates that both assays are not suitable to monitor r-hirudin
      anticoagulation. As an alternative approach a whole blood clotting assay based on
      the prothrombin-activating snake venom ecarin has been tested. In vitro
      experiments using r-hirudin-spiked whole blood samples showed a linear
      relationship between the concentration of hirudin added and the prolongation of
      the clotting times up to a concentration of r-hirudin of 4.0 micrograms/ml.
      Interassay coefficients (CV) of variation between 2.1% and 5.4% demonstrate the
      accuracy of the ecarin clotting time (ECT) assay. Differences in the
      interindividual responsiveness to r-hirudin were analyzed on r-hirudin-spiked
      blood samples obtained from 50 healthy blood donors. CV-values between 1.8% and
      6% measured at r-hirudin concentrations between 0.5 and 4 micrograms/ml indicate
      remarkably slight differences in r-hirudin responsiveness. ECT assay results of
      the ex vivo blood samples linearily correlate (r = 0.79) to the concentration of
      r-hirudin. Moreover, assay results were not influenced by treatment with
      aprotinin or heparin. These findings together with the short measuring time with
      less than 120 seconds warrant the whole blood ECT to be a suitable assay for
      monitoring of r-hirudin anticoagulation in cardiac surgery.

PMID- 9184404
TI  - Properties of a recombinant chimeric protein in which the gamma-carboxyglutamic
      acid and helical stack domains of human anticoagulant protein C are replaced by
      those of human coagulation factor VII.
AB  - A chimeric cDNA, encoding residues 1-46 (the gamma-carboxyglutamic acid module
      and its trailing helical stack) of human coagulant factor (f) VII, bound to
      residues 47-419 of human anticoagulant protein C (PC), was constructed and
      expressed. The resulting protein, r-[delta GD-HSPC/[symbol: see text] GD
      HSfVII]PC, was properly processed with regard to signal/propeptide release,
      cleavage of the K156R dipeptide, Gla and Hya contents, and the presence of
      glycosylation. The mutant protein displayed normal dependencies on Ca2+ for
      adoption of its metal ion-dependent conformation and for binding to acidic
      phospholipid vesicles. The chimera failed to recognize a monoclonal antibody
      (MAb) specific for the Ca(2+)-induced conformation of the Gla domain (GD) of PC,
      but did react with another MAb directed in part to the Ca(2+)-dependent
      conformation of the GD of fVII. Further, this chimeric protein possessed similar
      steady state constants as wild-type r-PC toward activation by thrombin and
      thrombin/thrombomodulin. The activated form of the chimera was very similar to
      that of its wild-type counterpart in its whole plasma anticoagulant activity, as
      well as its activity toward inactivation of coagulation factor VIII. The chimeric
      protein did not bind to the fVII cofactor, tissue factor, showing that the GD/HS
      domain region of fVII is insufficient for that particular interaction. The
      results demonstrate that the GD/HS of fVII, when present in the PC and APC
      background, serves to maintain the Ca2+/PL-related functions of these latter
      proteins, and suggest that the Ca2+ and PL-dependent interactions of the GD-HS of
      PC are sufficiently general in nature such that the GD-HS regions of other
      proteins of this type can satisfy most of the requirements of PC and APC. The
      data presented also offer support for the independent nature of the domain unit
      consisting of the GD/HS module.

PMID- 9184405
TI  - Potentially clinically important inaccuracies in testing for the lupus
      anticoagulant: an analysis of results from three surveys of the UK National
      External Quality Assessment Scheme (NEQAS) for Blood Coagulation.
AB  - The identification of the presence of antiphospholipid in plasma is recognised to
      be of diagnostic and prognostic importance in subjects with thrombotic disease,
      recurrent miscarriage or collagen vascular disorders. A number of coagulation
      assays are currently employed for the detection of lupus anticoagulant (LA), many
      of which are influenced by reagent dependent and methodological variables. In the
      present study lyophilised plasma samples from three subjects with "strong",
      "weak" and "absent" LA were tested in 220 centres. The most commonly used tests
      for LA were Activated Partial Thromboplastin Time (APTT), Dilute Russell Viper
      Venom Time (DRVVT) and Kaolin CLotting Time (KCT). Median DRVVT ratios were 1.75,
      1.17 and 1.10 for the three samples. The presence of a strong LA was not detected
      by 4% of laboratories. The correct diagnosis was made by 94% of users of DRVVT
      and 85% of users of KCT. A weak LA was not detected by over half of centres.
      Correction was observed on addition of plasma and also in platelet
      neutralisation. The correct diagnosis was made by 37% of users of DRVVT and 27%
      of users of KCT. Lupus Anticoagulant was falsely considered to be present in a
      Factor IX deficient plasma by approximately one quarter of laboratories. Amongst
      users of DRVVT and KCT absence of LA in this sample was correctly reported by 73%
      and 69% of centres respectively. The accuracy of testing for LA in the present
      study is suboptimal and this is likely to have important clinical consequences.
      There is clearly a need for greater conformity in the selection and performance
      of LA tests to facilitate accurate diagnosis of this important group of
      disorders.

PMID- 9184406
TI  - Restricted epitope specificity of anti-FVIII antibodies that appeared during a
      recent outbreak of inhibitors.
AB  - We recently described an outbreak of anti-factor VIII (FVIII) antibodies in a
      population of haemophilia A patients non-responsive to FVIII (1). To find out
      what part of the FVIII molecule had been altered, we purified specific anti-FVIII
      antibodies from the plasma of the five patients showing high titres of
      inhibitors. An average of 100 micrograms antibodies per ml of initial plasma was
      recovered by immunoadsorption on insolubilised FVIII. The antibodies followed the
      normal isotypic distribution, including the presence of specific IgG2 antibodies;
      the relative increase in IgG4 that is usually observed in patients with long
      standing inhibitors, was not present. The regions of FVIII to which human
      antibodies bound were determined by a competition assay using a panel of murine
      monoclonal antibodies: two major regions were identified, one located in the A2
      heavy chain domain, and the other made of determinants of both the A3 and C2
      light chain domains. Affinity-purified antibodies inhibited the function of FVIII
      as determined in a chromogenic assay. However, variations existed in the
      affinities with which antibodies bound to soluble FVIII. This study shows that
      the immunogenicity of two particular regions of FVIII has been altered. A
      screening for alterations located in these two regions should possibly be
      included in the preclinical evaluation of FVIII concentrates.

PMID- 9184407
TI  - Extravascular administration of factor IX: potential for replacement therapy of
      canine and human hemophilia B.
AB  - Current therapy for hemophilia B requires large intravenous doses of factor IX
      (F.IX) given in the clinic or at home. Although home therapy is possible for many
      patients, it is often complicated by factors such as the lack of good venous
      access. Very little is known about extravascular routes for administering
      proteins like F.IX (57 kD) or other vitamin K-dependent procoagulant factors into
      the circulation. Questions about the absorption rate from extravascular
      administration as well as plasma recovery and bioavailability have arisen
      recently with the growing availability of highly purified procoagulant proteins
      and increased interest in gene therapy of hemophilia B. Therefore, a group of
      studies were undertaken to determine the absorption rate, plasma recovery, and
      bioavailability of high purity, human plasma-derived F.IX concentrates
      administered via extravascular routes in hemophilia B dogs and in one human
      hemophilia B subject. Five hemophilia B dogs were given human F.IX via either a
      subcutaneous (s.c.), intramuscular (i.m.), intraperitoneal (i.p.) or intravenous
      (i.v.) route. In a subsequent study, a single SC administration of human F.IX was
      compared to an identical i.v. dose of F.IX in the human hemophilia B subject. All
      extravascular routes of F.IX administration in both the canine and human gave
      lower levels of circulating plasma F.IX than the i.v. route, however all routes
      resulted in measurable F.IX activity. Of the extravascular routes, the i.m.
      injection in the canine resulted in a bioavailability of 82.8%, while the s.c.
      injection resulted in a bioavailability of 63.5%. F.IX reached the plasma
      compartment by all extravascular routes used, confirming that F.IX can be
      absorbed extravascularly. The duration of measurable F.IX activity following
      extravascular administration is prolonged beyond that typically seen with i.v.
      administration. These data show that significant levels of F.IX may be obtained
      via s.c. injection in canine and human hemophilia B subjects and further
      highlight the potential of extravascular routes of administration for future
      experimental and clinical uses of F.IX and other procoagulant proteins.

PMID- 9184408
TI  - The identification and significance of a Thr-->Pro polymorphism in kringle IV
      type 8 of apolipoprotein(a).
AB  - Elevated plasma levels of lipoprotein(a) [Lp(a)] represent a significant
      independent risk factor for the development of atherosclerosis. Interindividual
      levels of apo(a) vary over 1000-fold and are mainly due to inheritance that is
      linked to the locus of the apolipoprotein(a) [apo(a)] gene. The apo(a) gene
      encodes multiple repeats of a sequence exhibiting up to 85% DNA sequence homology
      with plasminogen kringle IV (K.IV), a lysine binding domain. In our search for
      sequence polymorphisms in the K.IV coding domain, we identified a polymorphism
      predicting a Thr-->Pro substitution located at amino acid position 12 of kringle
      IV type 8 of apo(a). The functional and clinical significance of this
      polymorphism was analysed in a case-control study and by comparing the in vitro
      lysine binding characteristics of the two Lp(a) subtypes. The case-control study
      (involving 153 subjects having symptomatic atherosclerosis and 153 age and gender
      matched normolipidemic controls) revealed a overall allele frequency for the
      Thr12-->Pro substitution in kringle IV type 8 of 14% and a negative association
      between presence of the Pro12-subtype and symptomatic atherosclerosis (p < 0.03).
      The in vitro lysine binding studies, using Lp(a) isolated from subjects
      homozygous for either Thr12 or Pro12 in K.IV type 8, revealed comparable lysine
      Sepharose binding fractions for the two subtypes. The binding affinity (Kd) for
      immobilised plasmin degraded des-AA-fibrin (Desafib-X) was also comparable for
      the two subtypes, however a decreased maximal attainable binding (Bmax) for
      immobilised desafib-X was observed for the Pro12-subtype Lp(a).

PMID- 9184409
TI  - PCR-RFLP detection of PAI-2 gene variants: prevalence in ethnic groups and
      disease relationship in patients undergoing coronary angiography.
AB  - PAI-2 is a fibrinolytic inhibitor produced predominantly by monocytes. Most PAI-2
      is intracellular making study in clinical conditions difficult. Abnormalities in
      production may be associated with inflammation and fibrinolysis at sites of
      tissue damage such as the atherosclerotic plaque. PAI-2 gene variants have been
      described: variant A consists of Asn120, Asn404 and Ser413 and variant B consists
      of Asp120, Lys404 and Cys413. We designed a PCR-RFLP assay using primers spanning
      the region containing Asn/Lys404 and Ser/Cys413. Variant B contains an MwoI
      restriction site. We analysed 302 Pima Indians and 286 healthy Caucasian
      volunteers. To investigate relationships between genotype and vascular disease we
      analysed 333 Caucasian patients undergoing coronary angiography. Gene variant B
      was more common in the Pimas than in Caucasians (p < 0.0001). There was no
      significant difference in genotype distribution between the volunteers and
      patients. In the patients there was no association between genotype and either a
      history of MI or extent of coronary atheroma.

PMID- 9184410
TI  - Tridegin, a novel peptidic inhibitor of factor XIIIa from the leech, Haementeria
      ghilianii, enhances fibrinolysis in vitro.
AB  - Tridegin is a potent inhibitor of factor XIIIa from the leech, Haementeria
      ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated
      fibrin degradation as shown by the absence of D-dimer and approximately halves
      the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse
      more rapidly when either streptokinase, tissue plasminogen activator or hementin
      is added 2 h after clot formation. The effect of Tridegin is markedly increased
      if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are
      lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is
      present, the rate of lysis returns almost to that of platelet-free clots. These
      studies indicate the important role of platelets in conferring resistance to
      commonly used fibrinolytic enzymes and suggest that protein cross-linking is an
      important step in this effect. Moreover they indicate that Tridegin, a small
      polypeptide, may have potential as an adjunct to thrombolytic therapy.

PMID- 9184411
TI  - The Fab-fragment of a PAI-1 inhibiting antibody reduces thrombus size and
      restores blood flow in a rat model of arterial thrombosis.
AB  - The effect of PRAP-1, a Fab-fragment of a PAI-1-inhibiting polyclonal antibody,
      on thrombus size and arterial blood flow was studied in a rat model of arterial
      thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the
      rapid formation of an occlusive thrombus with a morphology similar to that of
      arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of
      fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.)
      prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did
      not affect the thrombus size per se, but caused a reduction in the
      interindividual variation of the size of the thrombus (p < 0.05). Thus, heparin
      was included in all the subsequent experiments. An i.v. infusion of t-PA (1
      mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the
      perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (P < 0.001).
      PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by
      an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the
      administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower
      PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold
      increase in the time to occlusion (p = 0.034), and the thrombus size was
      decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose
      were a 6.5 fold increase in perfusion rate (p < 0.001), a 1.6 fold increase in
      time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016).
      It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate
      decrease in thrombus size and partly restores blood flow in a rat model of
      arterial thrombus. This finding suggests a potential role for an inhibitor of PAI
      1 in the treatment of arterial thrombosis.

PMID- 9184412
TI  - Activation of the fibrinolytic system in patients with coronary artery disease
      and hyperfibrinogenemia.
AB  - Elevated fibrinogen levels as well as an impaired activity of the fibrinolytic
      system are regarded as important cardiovascular risk factors. To elucidate a
      potential interrelation between fibrinogen as an indicator of a hypercoagulable
      state and the endogenous fibrinolytic function hemostatic and rheological as well
      as lipid parameters were determined in 224 consecutive patients, who underwent
      elective coronary angiography. In the selected study population of 81 men and 19
      women with fibrinogen concentration either > or = 3.5 g/l (n = 70) or < or = 2.5
      g/l (n = 30) hyperfibrinogenemia was found to be significantly associated with
      increased concentrations of plasmin-alpha 2-antiplasmin complex [PAP [median (25.
      75. percentile)], 534 (361-680) micrograms/l vs. 289 (243-440) micrograms/l; p <
      0.001] and tissue plasminogen activator (t-PA) antigen [9 (6-11) micrograms/l vs
      8 (5-9) micrograms/l; p < 0.05] while this association was lost in the subgroup
      of patients with angiographically normal coronary arteries (n = 26). In addition
      to these findings fibrinogen was significantly correlated with PAP (r = 0.40, p <
      0.001; n = 224) and t-PA antigen (r = 0.2, p < 0.01; n = 224) after adjustment
      for age, diabetes mellitus, lipid parameters and leucocyte counts. It can be
      argued that elevated fibrinogen levels in patients with coronary artery disease
      are concomitant with an activation of the fibrinolytic system.

PMID- 9184413
TI  - Desmopressin (DDAVP) enhances platelet adhesion to the extracellular matrix of
      cultured human endothelial cells through increased expression of tissue factor.
AB  - The effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue
      factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by
      human umbilical vein endothelial cells cultures (HUVEC), was studied under
      different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30
      ng/ml) and then detached from their ECM. The reactivity towards platelets of this
      ECM was tested in a perfusion system. Coverslips covered with DDAVP-treated ECMS
      were inserted in a parallel-plate chamber and exposed to normal blood
      anticoagulated with low molecular weight heparin (Fragmin, 20 U/ml). Perfusions
      with run for 5 min at a shear rate of 800 s-1. Deposition of platelets on ECMs
      was significantly increased with respect to control ECMs when DDAVP was used at 5
      and 30 ng/ml (p < 0.05 and p. < 0.01 respectively). The increase in platelet
      deposition was prevented by incubation of ECMs with an antibody against human
      tissue factor prior to perfusion. Immunofluorescence studies positively detected
      tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under
      standardized conditions revealed a statistically significant increase in the
      procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP
      (p < 0.01 vs. control samples). Northern blot analysis revealed increased levels
      of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate
      that DDAVP in vitro enhances platelet adhesion to the ECMs through increased
      expression of tissue factor. A similar increase in the expression of tissue
      factor might contribute to the in vivo hemostatic effect of DDAVP.

PMID- 9184414
TI  - The integrin alpha 2 beta 1 (GPIa/IIa)-I-domain inhibits platelet-collagen
      interaction.
AB  - The integrin alpha 2 beta 1 is a major cellular receptor for collagen. The alpha
      2 subunit contains an +/- 200 amino acids inserted domain (I-domain) in the N
      terminal region. A certain degree of homology exists between the I-domains found
      in integrins, collagen and the A-domains of vWF. The alpha 2-I-domain encoding
      region (aa residues D145 to S334) was obtained by RT-PCR from mRNA of non
      stimulated human PBL's. The primers were designed to introduce the necessary
      restriction sites for cloning of the DNA fragment in frame downstream of the malE
      gene, as well as a stop codon after the last triplet. The resulting construct
      pMAL-c2-alpha 2-I allows the expression of the I-domain, fused to the C-terminus
      of maltose binding protein (mal). The alpha 2-I-mal is purified from the
      bacterial extract by affinity chromatography on an amylose column. The purified
      alpha 2-I-mal has been characterized by ELISA's. The alpha 2-I-mal bound to
      immobilised collagen type I in a concentration dependent manner and could be
      blocked by the functional monoclonal anti-alpha 2 beta 1 antibody 6F1. The
      interaction of alpha 2-I-mal with collagen furthermore is Mg(2+)-dependent since
      the binding was inhibited in the presence of 10 mM EDTA or 10 mM Ca2+ but
      sustained in the presence of 10 mM Mg2+. Finally, alpha 2-I-mal itself was able
      to inhibit adhesion of washed platelets to collagen immobilised on a
      microtiterplate in a dose-dependent manner (alpha 2-I-mal IC50:0.7 microM) as
      well as platelet aggregation induced by collagen type I (alpha 2-I-mal IC50:0.7
      microM). With these results we could confirm that the alpha 2-I-domain represents
      the collagen-binding site of alpha 2 beta 1 and we furthermore could indicate
      that this domain is able to prevent platelet adhesion to collagen and collagen
      induced platelet aggregation, pointing to the primordial role of alpha 2-I-mal
      and hence of alpha 2 beta 1 in platelet-collagen interaction.

PMID- 9184416
TI  - Defective signal transduction through the thromboxane A2 receptor in a patient
      with a mild bleeding disorder: deficiency of the inositol 1,4,5-triphosphate
      formation despite normal G-protein activation.
AB  - We describe an 11-year-old girl with a mild bleeding disorder since early
      childhood. The disorder was characterized by a prolonged bleeding time, and the
      patient's platelets showed defective aggregation responses to thromboxane A2
      (TXA2) mimetic U46619 and arachidonic acid. In contrast, the platelets showed
      normal responses to thrombin and Ca ionophore A23187. When the platelet TXA2
      receptor was examined with the [3H]-labeled TXA2 agonist U46619, the equilibrium
      dissociation rate constants (kd) and the maximal concentration of binding sites
      (Bmax) of the patient's platelets were within normal ranges. Normal GTPase
      activity was also induced in the patient's platelets by stimulation with U46619,
      however, inositol 1,4,5-triphosphate (IP3) formation was not induced by U46619.
      These results suggests that the patient's platelets had a defect in phospholipase
      C activation beyond TXA2 receptors.

PMID- 9184415
TI  - Deficiency of (33P)2MeS-ADP binding sites on platelets with secretion defect,
      normal granule stores and normal thromboxane A2 production. Evidence that ADP
      potentiates platelet secretion independently of the formation of large platelet
      aggregates and thromboxane A2 production.
AB  - By the term "Primary Secretion Defect" (PSD), we mean a common heterogeneous
      group of congenital defects of platelet secretion, characterized by a normal
      primary wave of platelet aggregation induced by ADP and other agonists, a normal
      concentration of platelet granule contents, and normal production of thromboxane
      A2. The biochemical abnormalities responsible for PSD are not well known. Since a
      secretion defect similar to PSD is found in platelets that are severely deficient
      of binding sites for the ADP analogue 2MeS-ADP and do not aggregate in response
      to ADP, we tested the hypothesis that PSD platelets have moderately decreased
      2MeS-ADP binding sites, which may be sufficient for normal ADP-induced
      aggregation but not for potentiating platelet secretion. The specific binding of
      [33P]2MeS-ADP to platelets from 3 PSD patients (347, 443 and 490 sites/platelet;
      KD 2.8-3.9 nM) was lower than to platelets from 24 normal subjects (647 [530
      1102]; KD = 3.8 [2.3-7.3]) (median [range]). Normal values were found in a fourth
      PSD patient (710; KD 3.7). The degree of inhibition of PGE1-induced cAMP increase
      by 0.1 microM ADP was lower in patients than in controls. The secretion induced
      by the endoperoxide analogue U46619 from normal, acetylsalicylic acid-treated
      platelets under conditions that prevented the formation of large aggregates was
      potentiated by 1 mumol/l ADP and inhibited by apyrase. These findings indicate
      that a partial deficiency of the platelet ADP receptor(s) might be responsible
      for the defect of platelet secretion in some PSD patients and that ADP
      potentiates platelet secretion independently of the formation of large aggregates
      and thromboxane A2 production.

PMID- 9184417
TI  - Aggregation of human blood platelets by remnant like lipoprotein particles of
      plasma chylomicrons and very low density lipoproteins.
AB  - Remnant like lipoprotein particles (RLP) of partially catabolised human plasma
      chylomicrons (CM) and very low density lipoproteins (VLDL) were separated from CM
      and VLDL using two monoclonal antibodies, anti apo B-100 (JI-H) and anti apo A-I
      (H-12) coupled to Sepharose 4B gel to form an immunoaffinity column. Lipoproteins
      containing apo B-100 or apo E, including VLDL and LDL adsorb to (JI-H)-gel, while
      CM and HDL with apo A-I adsorb to (H-12)-gel. The unbound fraction (RLP) is rich
      in apo B-48, apo E and apo E rich apo B-100 which has not been recognized by JI
      H. The RLP fraction with a total triglyceride of 12.35 +/- 6.22 mg/ml; total
      cholesterol, 0.32 +/- 0.08 mg/ml and total protein, 0.72 +/- 0.12 mg/ml (mean +/-
      S.E.M, n = 9) was added to blood from healthy persons at 2.5-200 microliters/ml
      and agitated gently at 37 degrees C for 40 s. Platelet aggregation was assessed
      by measuring the loss of single platelets. At 2.5-10 microliters, RLP induced
      platelet aggregation increased with the dose of RLP, but decreased at 25-200
      microliters. Scanning electron microscopy revealed that within 20 s of agitation
      in the presence of RLP, activated platelets had appeared on the red cell membrane
      and within 40 s of agitation, platelet aggregates had formed on the red cells.
      The platelet responses were unaffected by aspirin (10 or 20 micrograms/ml) but
      were inhibited by cilostazol, a phosphodiesterase type III inhibitor (0.4 to 1.6
      micrograms/ml). It is likely that the platelet effect of RLP is a consequence of
      RLP dependent red cell-platelet interaction. This is the first report of platelet
      aggregation induced by RLP without an added platelet agonist.

PMID- 9184418
TI  - Platelet hyporeactivity in very low birth weight neonates.
AB  - Very few studies have examined platelet function in very low birth weight (VLBW)
      preterm neonates, because of the relatively large volumes of blood required. In
      this study, platelet function in clinically stable VLBW neonates was examined by
      whole blood flow cytometry, which requires only 5 microliters of whole blood per
      assay. The following monoclonal antibodies were used: S12 (P-selectin-specific,
      reflecting alpha granule secretion), PAC1 (directed against the fibrinogen
      binding site exposed on the GPIIb-IIIa complex of activated platelets), F26
      (directed against a conformational change in fibrinogen bound to the GPIIb-IIIa
      complex), and 6D1 (directed against the von Willebrand factor binding site on the
      GPIb-IX-V complex). VLBW neonates, like normal adults, did not have circulating
      activated platelets, as determined by the lack of binding of S12, PAC1, and F26
      in the absence of an added agonist. VLBW neonatal platelets were markedly less
      reactive than adult platelets to thrombin, ADP/epinephrine, and U46619 (a stable
      thromboxane A2 analogue), as determined by the extent of increase in the platelet
      binding of S12, PAC1, and F26, and the extent of decrease in the platelet binding
      of 6D1. In summary, compared to adults, the platelets of VLBW neonates are
      markedly hyporeactive to thrombin, ADP/epinephrine and a thromboxane A2 analogue
      in the physiologic milieu of whole blood, as determined by: 1) the increase in
      platelet surface P-selectin; 2) the exposure of the fibrinogen binding site on
      the GPIIb-IIIa complex; 3) fibrinogen binding; and 4) the decrease in platelet
      surface GPIb. This platelet hyporeactivity may be a factor in the propensity of
      VLBW neonates to intraventricular hemorrhage. In addition to its previously
      defined use as a test of platelet hyperreactivity, the present study suggests
      that whole blood flow cytometry may be useful in the clinical assessment of
      platelet hyporeactivity.

PMID- 9184419
TI  - von Willebrand factor without the A2 domain is resistant to proteolysis.
AB  - von Willebrand factor (vWF) is a complex multimeric plasma glycoprotein, that
      plays a critical role in the mediation of platelet adhesion to the damaged
      vascular wall, and functions as a carrier protein for factor VIII. vWF has a
      domain structure consisting of repeated A, B, C, and D domains. The A1 domain is
      involved in binding to the platelet receptor glycoprotein (GP) Ib, and the A3
      domain has a binding site for collagen. A function of the A2 domain has not been
      described, although point mutations identified in von Willebrand disease (vWD)
      type 2A patients are localized in this domain. To study the role of the A2 domain
      a deletion mutant was constructed which lacked the A2 domain, delta A2-vWF.
      Previous studies have shown that this approach is a powerful tool to study the
      function of a domain in a protein since it does not affect the activity of other
      domains. After expression in baby hamster kidney (BHK) cells, delta A2-vWF was
      compared to wild-type (WT) vWF, and to delta A1-vWF (Lankhof et al., Blood 86:
      1035, 1995). Ristocetin induced platelet binding was slightly increased but
      botrocetin induced platelet binding was normal as was binding to heparin and
      collagen type III. Adhesion studies to surface coated purified delta A2-vWF or to
      delta A2-vWF preincubated on collagen under flow conditions showed no
      abnormalities. Incubation with normal human plasma showed that delta A2-vWF like
      WT-vWF was not sensitive to proteolysis. After addition of urea, WT-vWF becomes
      sensitive to the protease, indicating that unfolding of the molecule is necessary
      for exposure of the cleavage site. delta A2-vWF tested under the same conditions
      was resistant, indicating that the protease sensitive site is located in the A2
      domain.

PMID- 9184421
TI  - Erythropoietin potentiates thrombus development in a canine arterio-venous shunt
      model.
AB  - Erythropoietin (EPO) has been previously shown to affect platelet as well as red
      cell production. In addition, recent studies demonstrated that platelets from EPO
      treated dogs are hyperreactive towards thrombin when compared to age-matched,
      control platelets. This report extends these observations by quantitating the
      thrombogenic potential of EPO in dogs. Dogs with arterio-venous (A-V) shunts
      received 100 U EPO/kg/day for 6 days, and thrombogenicity was serially monitored
      by insertion of a thrombotic surface into the A-V shunt. The resulting
      experimental thrombi were analyzed for platelet and erythrocyte content after
      formalin-fixation and chymotrypsin digestion, a technique which allows non
      isotopic quantitation of cellular components. By day 5 of EPO-administration all
      animals demonstrated a significant increase in platelet and red cell content of
      the experimental thrombi; the average increase in platelet number was 2.94 +/-
      0.12 fold (mean +/- 1 SE; n = 3; p = 0.006) above baseline while that for red
      cells was 2.46 +/- 0.18 fold above baseline (p = 0.023). After cessation of EPO,
      thrombogenicity returned to normal. During EPO-treatment, the percentage of
      thiazole orange-positive (TO+) platelets increased significantly to 17.2 +/- 1.6%
      (mean +/- 1 SE; n = 3) on day 5 compared to a pre-treatment level of 8.5 +/- 0.9%
      (p = 0.029). Although the percentage of TO+ erythrocytes also increased during
      the short course of EPO administration, the change was not significant. Despite
      the increases in TO+ cells, total platelet and erythrocyte counts did not change
      significantly within the time frame of these experiments. Fibrin/fibrinogen
      content of the experimental thrombi was unaltered with EPO-treatment. These data
      demonstrate that human EPO is pro-thrombotic in dogs and, in conjunction with
      earlier studies, suggest that hyperreactive platelets may be responsible for the
      potentiated thrombogenicity.

PMID- 9184420
TI  - Endothelial cell protein S synthesis is upregulated by the complex of IL-6 and
      soluble IL-6 receptor.
AB  - We have recently demonstrated that the proinflammatory cytokine, interleukin-6
      (IL-6), could upregulate the production of protein S in the human hepatoma cell
      line, HepG-2, but not in endothelial cells. In this study, we have demonstrated
      that the combination of exogenous IL-6 and soluble IL-6 receptor (sIL-6R) could
      significantly upregulate protein S production in both primary human umbilical
      vein endothelial cells (HUVEC) and in the immortalized human microvascular
      endothelial cell line, HMEC-1. The IL-6/sIL-6R complex was also able to rapidly
      induce tyrosine phosphorylation of the IL-6 transducer, gp130. Neutralizing
      antibodies directed against either IL-6 or gp130 blocked protein S upregulation
      by the IL-6/sIL-6R complex. It was also observed that exogenous sIL-6R could also
      upregulate protein S by forming a complex with IL-6 constitutively produced by
      the endothelial cell. Two other cytokines which also utilize the gp130 receptor,
      oncostatin M (OSM) and leukemia inhibitory factor (LIF), were also able to
      upregulate endothelial cell protein S. This study demonstrates a mechanism that
      allows endothelial cells to respond to IL-6 and also illustrates the potential
      importance of circulating soluble receptors in the regulation of the
      anticoagulation pathway.

PMID- 9184423
TI  - A reference material for harmonisation of D-dimer assays. Fibrinogen Subcommittee
      of the Scientific and Standardization Committee of the International Society of
      Thrombosis and Haemostasis.
AB  - The term "D-dimer assay" suggests, that these assays report the concentrations of
      the end-stage degradation product of crosslinked fibrin. This hardly occurs in
      patients. Degradation products of cross-linked fibrin rather occur with a wide
      range of molecular weights, and comprise various numbers of the D-dimer motif.
      Moreover, the numerical values obtained with different "D-dimer" assays vary
      widely. The variations are probably due to differences in reactivity of the
      various monoclonal antibodies used with the various D-dimer containing
      degradation products as they occur in patients; and to the various calibrators
      with a value assigned by the manufacturers. For the reasons indicated above a
      calibrator in the strict sense (e.g., pure D-dimer) is not feasible. This study
      shows that: it appears feasible to generate a conversion factor for each of the
      "D-dimer" assays studied, which will make the widely varying results obtained
      with these kits comparable; that the conversion factors can be based on a pool of
      real patient samples; and that the conversion factors are pool-independent. The
      next and final step in this study is to prepare and make available an
      international reference material for use by manufacturers and others facing a
      comparison problem. This is being carried out, in collaboration with the NIBSC
      (Dr. P. Gaffney), and the material is expected to be available in early 1997.

PMID- 9184422
TI  - Comparison of dose regimens for the administration of recombinant pro-urokinase
      in a canine thrombosis model.
AB  - Pro-urokinase represents an important addition to the array of thrombolytic drugs
      currently available for clinical use because of its high clot specificity but
      distinctly different mechanism compared with that of t-PA. Recombinant pro
      urokinase (r-proUK) is a single-chain precursor of high molecular weight
      urokinase which has been expressed in a mouse myeloma cell line. The present
      study was conducted to determine the dosing regimen which would produce optimal
      clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using
      a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radio
      labelled clot which was formed in the heat-damaged femoral arteries of 39 male
      beagle dogs. The animals were divided into six heparinized treatment groups, each
      receiving one of five dosing regimens or the vehicle for r-proUK. The total dose
      (80,000 U/kg) was divided into an initial loading bolus, followed by either a
      second bolus or by infusions for various time periods, as shown below: Group
      Treatment Regimen % Lysis 1 r-proUK Bolus/bolus, 50%/50% at 0 and 15 min 52 +/- 7
      2 r-proUK Bolus/bolus, 50%/50% at 0 and 30 min 62 +/- 7 3 r-proUK Bolus/infusion,
      20%/80% infused to 30 min 41 +/- 8 4 r-proUK Bolus/infusion, 20%/80% infused to
      60 min 66 +/- 5 5 r-proUK Bolus/infusion, 50%/50% infused to 30 min 73 +/- 4 6
      Vehicle Bolus/infusion, 50%/50% infused to 30 min 12 +/- 6 It was concluded that
      optimal clot lysis and restoration of femoral flow was accomplished using a
      regimen in which 50% of the dose was given as a bolus, followed immediately by
      the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose
      used in this study, r-proUK did not produce degradation of fibrinolytic or
      hemostatic plasma proteins.

PMID- 9184424
TI  - Corrected DNA sequence of the platelet glycoprotein IX gene.

PMID- 9184425
TI  - Inadequate quality of a blood collection tube containing an
      anticoagulant/platelet inhibitor mixture.

PMID- 9184426
TI  - Presence of FV Leiden and MTHFR mutation in a patient with complicated
      pregnancies.

PMID- 9184427
TI  - Antiphospholipid syndromes with anti-human beta 2-glycoprotein I antibodies
      despite negative reactivity in conventional aPL and LA assays.

PMID- 9184428
TI  - A brief review of studies evaluating the adverse effects of aprotinin therapy in
      aortocoronary bypass surgery.

PMID- 9184429
TI  - Characterisation of Fibrinogen Oslo IV by electrospray mass spectrometry.

PMID- 9184430
TI  - Kinetic parameters for plasminogen activation by tissue type plasminogen
      activator.

PMID- 9184431
TI  - Rapid blood test for the exclusion of venous thromboembolism in symptomatic
      outpatients.

PMID- 9184432
TI  - Coronary stenting in a hemophilic patient.

PMID- 9184434
TI  - Experimental vasospasm produced without blood cell components--hypothesis for the
      development of cerebral vasospasm.
AB  - A canine model of cerebral vasospasm using noncellular blood material (fibrin
      glue) was designed to investigate the effect of cerebrospinal fluid obstruction.
      The arachnoid membrane covering the cerebral arteries in the basal cistern was
      dissected and fibrin glue was applied to the adventitial surface of the arteries
      in three groups of animals. In Group 1, the arachnoid membrane was extensively
      dissected and fibrin glue was widely applied to the cerebral arteries. In Group
      2, the dissection and coating was less extensive. Group 3 was a control group in
      which the arachnoid membrane was dissected but fibrin glue was not applied.
      Cerebral angiography 1 week later clearly demonstrated vasospasm in all six dogs
      in Group 1 and in four of six dogs in Group 2. Vasospasm did not occur in Group
      3. The dogs were sacrificed and the arteries in the basal cistern were removed.
      Histological investigation showed typical findings of vasospasm and inertness of
      fibrin glue to the tissue. Cerebral vasospasm can be induced by a noncellular
      material from the blood densely applied to the arterial surface suggesting that
      obstruction of cerebrospinal fluid circulation around the artery may be important
      in the development of cerebral vasospasm.

PMID- 9184435
TI  - Clinical analysis of recurrent subarachnoid hemorrhage after neck clipping
      surgery.
AB  - The clinical features of recurrent subarachnoid hemorrhage (SAH) after neck
      clipping surgery were investigated in a series of 1,436 consecutive patients
      treated between 1980 and 1994, and seven patients treated prior to 1980.
      Recurrent SAH occurred within 1 month in seven patients and between 1.5 and 20
      years in 20 patients (mean interval 9.2 years) from the first surgery. The
      patients were aged from 31 to 76 years (mean 49.8 years) at the first SAH. There
      were 19 females and eight males. Recurrent SAH occurred at the same site as the
      prior aneurysms in 12 cases, at an infundibular dilatation in three cases, de
      novo aneurysms in nine cases, untreated multiple aneurysms in two cases, and
      unknown in one case. The main causes for early recurrent SAH were incomplete
      clipping or untreated multiple aneurysms, whereas late recurrent SAH was due to
      de novo aneurysms, untreated multiple aneurysms, or regrowth aneurysm at the
      prior site. The outcomes of late recurrent SAH were good in eight cases, moderate
      disability in two, severe disability in three, and dead in seven, whereas most
      cases of early recurrent SAH resulted in poor outcome. Immediate postoperative
      angiography is desirable in cases with incomplete clipping, because early
      recurrent SAH resulted in poor outcomes. De novo or regrowth aneurysms caused
      late recurrent SAH, so follow-up angiography is strongly recommended for young
      patients, even if complete clipping was achieved.

PMID- 9184436
TI  - Aneurysms located at the horizontal segment of the anterior cerebral artery or
      the middle cerebral artery.
AB  - Aneurysms at the horizontal segment of the middle cerebral artery or anterior
      cerebral artery are relatively rare. The characteristics of 13 cases were
      analyzed retrospectively. Six of the 13 cases had multiple aneurysms, nine had
      aneurysmal rupture, and three of these nine were complicated by intracerebral
      hematoma. Neck clipping of the aneurysm was performed in 11 cases and four
      developed new cerebral infarction in the territory of the perforating arteries.
      Overall mortality and morbidity was 15% and 38%, respectively. The outcome for
      patients with aneurysms at these sites was evidently poorer than for those with
      aneurysms at other sites.

PMID- 9184437
TI  - Enzyme immunoassay of glioma cell tenascin secretion and augmentation by tumor
      necrosis factor-alpha.
AB  - Expression of tenascin, an extracellular matrix glycoprotein, was measured in
      glioma cell lines using a newly established enzyme immunoassay. Secreted tenascin
      was found at concentrations greater than 800 ng/ml in eight of 14 glioma, three
      small cell lung carcinoma, two melanoma, and one sarcoma cell lines. The
      remaining six glioma and other carcinoma cell lines, and cell lines originating
      from normal tissues demonstrated low levels or no secretion into the supernatant.
      The glioma cell line, U-251-MG nu/nu, which has almost 100% transplantability in
      nude mice, had the highest expression level of tenascin among the glioma cell
      lines examined. Even low secretor glioma cell lines released high concentrations
      of tenascin, detectable by assaying the NP-40 solubilized cell lysates. Flow
      cytometric analysis revealed that tenascin was located on both the cell surface
      and primarily in the cytoplasm of glioma cells. When the glioma cell lines were
      exposed to tumor necrosis factor-alpha (TNF-alpha), levels of secreted tenascin
      increased between 36% and 380%, whereas transforming growth factor-beta induced
      only minimal changes. These results suggest that glioma cell lines may be
      classified according to the degree of tenascin secretion/expression: high
      secretor type, low secretor type, and non-expressing type. The increase in
      tenascin secretion by TNF-alpha suggests that the expression of tenascin in
      glioma growth and development may be mediated through a cytokine network.

PMID- 9184438
TI  - Rapidly-growing ectopic pituitary adenoma within the sphenoid sinus--case report.
AB  - A 75-year-old male with left abducens nerve paresis presented with an ectopic
      pituitary adenoma invading the posterior wall of the sphenoid sinus. The
      sphenoidal mass grew rapidly for 6 months with left ophthalmoplegia and was
      partially removed via the transsphenoidal approach. The histological examination
      showed a benign pituitary adenoma, but the MIB-1 proliferating cell index was
      6.8%, reflecting the clinically malignant behavior. The symptom gradually
      improved without tumor regrowth over 1.5 years after conventional irradiation.

PMID- 9184439
TI  - Hypervascularity in Lhermitte-Duclos disease--case report.
AB  - A 61-year-old male presented with a hypervascular variant of dysplastic
      gangliocytoma (Lhermitte-Duclos disease) manifesting as gait disorder. Computed
      tomography and magnetic resonance imaging both showed enhancement of the tumor
      after injection of contrast medium. Angiography demonstrated a tumor stain.
      Histological examination showed a double-layered structure comprising an outer
      layer of myelinated axons and an inner layer of dysplastic granular cells, and
      numerous dilated thin-walled blood vessels. Partial resection of the tumor
      resulted in resolution of the neurological deficit.

PMID- 9184440
TI  - Microcystic meningioma without enhancement on neuroimaging--case report.
AB  - A 63-year-old female presented with an unusual case of microcystic meningioma
      manifesting as a 4-year history of unsteady gait, dysarthria, and hearing loss.
      Computed tomography disclosed a large hypodense mass in the right
      cerebellopontine angle, clivus, and middle fossa, with slight contrast
      enhancement. T1-weighted magnetic resonance images demonstrated the lesion as a
      hypointense mass, which was little enhanced gadolinium-diethylenetriaminepenta
      acetic acid. Right carotid angiography revealed blood supply from the external
      carotid artery, but no tumor staining. The extracerebral tumor was subtotally
      removed. The histological diagnosis was microcystic meningioma. Light microscopy
      revealed abundant microcystic throughout the tumor tissue, and electron
      microscopy disclosed that the microcysts were mostly located in the extracellular
      spaces and only a few in the cytoplasm. Microcystic meningioma without
      enhancement is rare and should be differentiated from low-grade astrocytoma,
      epidermoid, or other non-enhanced tumor.

PMID- 9184441
TI  - Cerebellar gliomas with exophytic growth--three case reports.
AB  - Three patients presented with cerebellar hemispheric astrocytic tumors which
      showed an exophytic growth pattern. The neuroimaging appearances of these cases
      mimicked a cerebellopontine angle tumor in two cases, and a posterior fossa extra
      axial tumor in the other, which arose from the left cerebellar hemisphere with
      exophytic extension into the left crural and quadrigeminal cisterns and
      compressed the midbrain directly. All patients underwent surgical resection, and
      two patients also received adjuvant radiation therapy and chemotherapy.
      Intraoperative findings confirmed that the tumors had intramedullary origins from
      the cerebellar hemisphere, and extended exophytically into the subarachnoid space
      forming an extra-axial mass lesion. The histological diagnoses were mixed
      malignant oligo-astrocytoma (grade III), astrocytoma (grade II), and glioblastoma
      (grade IV). Cerebellar gliomas with exophytic growth to the cerebellopontine
      angle cistern should be considered in the differential diagnosis of
      cerebellopontine angle tumors.

PMID- 9184442
TI  - Trochlear and abducens nerve neurinomas accompanied by a cerebellopontine angle
      meningioma--case report.
AB  - A 66-year-old male presented with cerebellovestibular symptoms and hypesthesia of
      the V2 area of his face. Neuroimaging only detected a cerebellopontine angle
      (CPA) meningioma. The CPA meningioma was removed using the lateral suboccipital
      approach, which exposed small neurinomas arising from the trochlear and abducens
      nerves. Both neurinomas were removed intracapsularly. Postoperatively hypesthesia
      resolved, but other symptoms were unchanged. A karyotypic analysis of chromosome
      22 and estrogen receptor analysis suggested absence of neurofibromatosis II, but
      the cause(s) of the genesis of the multiple diverse tumors was not determined.
      This extremely rare combination of neurinomas and meningioma was probably
      incidental, as there are no reports of any case which a combination of the
      trochlear and the abducens nerve neurinomas, much less one accompanied by a
      meningioma.

PMID- 9184443
TI  - Supratentorial glioma manifesting as acute onset of pure motor hemiparesis--case
      report.
AB  - A 68-year-old male presented with an anaplastic astrocytoma deep in the
      sensorimotor cortex manifesting as acute pure motor hemiparesis suggestive of a
      vascular mechanism rather than tumor mass effect. Perfusion-weighted magnetic
      resonance (MR) imaging showed a significant decrease of blood flow in the
      sensorimotor area, where fluid-attenuated inversion recovery imaging demonstrated
      a prominently edematous area. Angiography also suggested ischemia with poor
      visualization of the precentral and central arteries. Diffusion-weighted MR
      imaging failed to identify the edema as cytotoxic or vasogenic due to technical
      problems. Brain tumors may manifest through impairment of peritumoral blood
      supply, which can be clarified by recent MR methods.

PMID- 9184444
TI  - [Autonomic nerves controlling ejaculation--base of nerve sparing operation for
      ejaculation].

PMID- 9184445
TI  - [Long-term results of short-course preoperative radiotherapy and radical
      cystectomy for bladder cancer].
AB  - BACKGROUND: The long-term effects of preoperative high-dose short-course
      radiotherapy for bladder cancer are controversial. METHODS: We reviewed 144
      patients with an invasive or grade 3 bladder cancer who underwent radical
      cystectomy with or without preoperative radiotherapy between 1978 and 1990.
      Preoperatively, short-curse radiation (16 Gy) was given to 100 patients,
      conventional pelvic radiation (median 31 Gy) to 12 patients and no radiation of
      32 patients. The median follow-up period was 7 years 11 months. One patient was
      lost to follow-up. RESULTS: The overall survival rates did not differ among the
      short-course, conventional and no-radiation groups. However, if limited to the
      patients with stage pT2 or higher, or with grade 2 or 3, the survival rates were
      significantly higher in the short-course radiation group than in the other
      groups. Although preoperative short-course radiation tended to lower the
      pathological stage, the presence or absence of down-staging did not influence the
      survival rates. CONCLUSION: Preoperative short-course radiotherapy may possibly
      improve the prognosis of cystectomized patients with clinical stage T2 or T3, or
      squamous cell cancer.

PMID- 9184446
TI  - [The concentration of Tamsulosin hydrochloride in the blood and prostatic tissue
      of the patients in benign prostatic hyperplasia].
AB  - BACKGROUND: The penetration of Tamsulosin hydrochloride into the blood and the
      prostatic tissue was examined. METHODS: Fifty-two patients with benign prostatic
      hyperplasia treated with transurethral resection of the prostate were entered in
      this study. This drug was administered orally in a dose of 2.0 mg once a day for
      7 to 179 days preoperatively. The blood samples were taken simultaneously at the
      time of the prostatic tissue sampling. RESULTS: 1. The correlation coefficient
      was hardly significant between aging and concentration of the drug in the blood
      or in the prostatic tissue. 2. The correlation coefficient was hardly significant
      between the duration of the drug administration and concentration of the drug in
      the blood or the prostatic tissue. 3. The correlation coefficient was significant
      between the concentration of the drug in the blood and the prostatic tissue. 4.
      The fifty-two patients showed no significant adverse reactions during
      administration of the drug. CONCLUSION: These results suggest that the drug can
      be administered safely to the aged even in a long-term and can be penetrated into
      the blood and the prostatic tissue with a positive correlation.

PMID- 9184447
TI  - [Estimation of renal transplant dysfunction by color Doppler sonography].
AB  - BACKGROUND: To clarify various conditions in the transplanted kidney, invasive
      biopsy must be performed in most cases. In this study, we measured blood flow in
      the transplanted kidney by color Doppler tomography to examine the usefulness of
      measuring renal blood flow in clarifying various conditions. METHOD: Blood flow
      in the transplanted kidney was measured using peak flow velocity (PFV) and an
      index of resistance, the pulsatility index (PI), as parameters. RESULT: In acute
      cellular rejection, there were no changes in blood flow in the segmental
      arteries, while there was a significant decrease in the blood flow in the
      interlobar artery. In acute vascular rejection, it was difficult to measure blood
      flow in the interlobar artery. The values of parameters were low even in the
      segmental arteries, suggesting markedly decreased blood flow. In chronic
      rejection, the values of the parameters were low in proportion to transplanted
      kidney function. In addition, parameters were examined with respect to vascular
      stenosis, fibrous stroma and edema in the histopathology of the transplanted
      kidney. As a result, vascular stenosis and fibrous stroma affected the segmental
      and interlobar arteries, severely reducing blood flow. It was also shown that
      interstitial edema reduced blood flow in the interlobar artery. CONCLUSION: Color
      Doppler tomography may facilitate diagnosis of certain conditions in the
      transplanted kidney biopsy.

PMID- 9184448
TI  - [Androgen receptor gene mutations in prostate cancer].
AB  - PURPOSE: Androgens are required for the development of normal prostate and
      prostate cancer, through their action via the androgen receptor (AR). Although
      prostate cancer is potentially curable in the early stages by radical
      prostatectomy, androgen ablation is standard treatment for metastatic prostate
      cancer. Metastatic prostate cancer is incurable despite temporary remission
      commonly achieved by androgen ablation therapy. To investigate the mechanism for
      the development of human prostate cancer, examination was made of AR gene
      mutations. MATERIALS AND METHODS: Thirty-two samples including 29 primary
      prostate cancers and 3 metastatic lymph nodes were examined from exons B to H of
      the AR gene by polymerase chain reaction of single-strand conformation
      polymorphism (PCR-SSCP) and direct-sequencing analysis. Three metastatic lymph
      nodes were removed from non-hormone treated stage D1 patients by radical
      prostatectomy. Six of 11 stage D2 patients were hormone-independent stage
      following androgen ablation therapy. RESULTS: One of 29 (3.4%) primary prostate
      cancers and 1 of 6 (16.7%) hormone-independent stage D2 patients showed the AR
      mutation. This AR mutation is a G to A transition at nucleotide 2677 that leads
      to substitution of glutamine (CAG) for the wild type arginine (CGG) at codon 629.
      The serum prostate specific antigen level of the patients increased to 480 ng/ml.
      Drugs for hormone therapy and duration of treatment had the same effects on the
      remaining 5 hormone-independent patients. No mutation was found in the other 28
      primary prostate cancer or 3 metastatic lymph node samples. CONCLUSIONS: The AR
      mutation may possibly be involved in the development of prostate cancer from the
      androgen-dependent to -independent stage during androgen ablation therapy.

PMID- 9184449
TI  - [Progression of renal disease in patients with reflux nephropathy. Follow-up
      study].
AB  - BACKGROUND: We previously estimated the turning point of reflux nephropathy
      irreversibly deteriorating to end stage renal disease, mainly based on findings
      in renal biopsy (Eur. Urol., 26: 153-159, 1994). In this study, we aim to
      evaluate clinical parameters which may be closely associated with progression of
      reflux nephropathy to end stage renal disease. SUBJECTS AND METHODS: Ninety five
      patients (84 children and 11 adults; 41 men and 54 women) with renal scar and/or
      reflux (>/ = grade 3), mean aged 9.4 +/- 9.1 years (3 months-53 years) were
      followed up for 3.7 years +/- 2.7 (6 months-18 years). Vesicoureteral reflux was
      bilateral in 64 and unilateral in 31; primary in 85 and secondary in 10 patients.
      Clinical parameters including body weight, height, blood pressure, 24 hour
      urinary protein excretion, serum creatinine, 99m Tc-DTPA GFR and 99 m Tc-DMSA
      uptake were monitored over time. All patients underwent antireflux surgery (with
      or without other reconstructive surgery) and open renal biopsy. Three patients
      progressing to end stage renal disease underwent subsequent biopsy. RESULTS: Over
      5 year observation period, the prevalence of new scare formation and further
      extension in scar was significantly higher in the group of renal functional
      deterioration (35%) than in the group of stable renal function (6.0%). Over the
      same period DMSA uptake decreased significantly (< 0.05) in the group of scar b
      (Smellie's classification), suggesting most kidneys of scar b eventually
      resulting in atrophic kidney (scar c). Proteinuria more than 100 mg/day appeared
      to be a critical level for predicting irreversible deterioration in renal
      function. Glomerular hypertrophy was closely related to the increase in urinary
      protein excretion and serum creatinine, contrary to the decrease in DTPA-GFR. In
      addition, bilateral renal scar b, glomerular hypertrophy (> 2 SD), proteinuria (>
      300 mg/day), low GFR (mean: 49 ml/min), and diastolic hypertension seemed to be
      implicated in the genesis of ESRD. CONCLUSION: Glomerular damage due to either
      reflux nephropathy or dysplasia may cause proteinuria. Proteinuria of 100 mg/day
      was significantly (p < 0.01) associated with 2 SD of glomerular hypertrophy on
      histology and clinical observation (suggesting hyperfiltration). Thereafter, a
      rapid increase in proteinuria followed by diastolic hypertension appears be
      significant for predicting ESRD.

PMID- 9184451
TI  - [Long-term clinical course of Peyronie's disease treated conservatively].
AB  - BACKGROUND: To evaluate the natural history of Peyronie's disease and to
      determine the suitable time for surgical treatment, we investigated changes of
      clinical findings of the disease over time. PATIENTS AND METHODS: We evaluated
      changes of plaque size, penile curvature and erectile dysfunction in 10 patients
      with Peyronie's disease. The mean follow-up period was 36.8 months. RESULTS: At
      the first examination, the mean plaque size of patients with erectile dysfunction
      was larger than that of those without erectile dysfunction, suggesting a positive
      association between size and erectile function. There was no significant
      relationship between plaque size and penile pain or penile curvature. The mean
      size of plaques decreased significantly compared with that at the first
      examination (p < 0.05). However, penile curvature, pain and erectile dysfunction
      persisted during the follow-up period in all but one patient, who showed
      improvement of penile curvature. CONCLUSION: These results suggest that we may
      recommend a shorter observation period until surgery that we have done for some
      patients who want to be surgically treated.

PMID- 9184450
TI  - [Clinical evaluation of donor renal artery reconstruction in kidney
      transplantation].
AB  - This retrospective study describes the experience of arterial reconstruction of
      donor kidney in our institute since 1982. MATERIALS AND METHODS: Of total 56
      living related kidney transplantations 15 required renal arterial reconstruction
      or ligation of donor kidneys. Renal arterial reconstruction was employed for 11
      cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric
      artery graft interposition [3], other [1], while simple ligation was employed for
      4. Bench surgery with microsurgical techniques was employed for the repair.
      Elective surgery was done for preoperatively defined multiple renal arteries [10]
      and aneurysm [1], while imperative surgery for intraoperatively detected
      accessory arteries [2] and surgical injuries [2]. Postoperative patency of
      arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy.
      RESULTS: The mean total ischemic time of reconstructed cases was 135 min., while
      that of ligated ones was 67 min. None of them required hemodialysis due to acute
      tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11
      reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%).
      Two failure attempts of arterial reconstruction cases were all imperative ones.
      Postoperative GFR of the graft was well preserved in all cases. CONCLUSION: We
      conclude that (1) Ligation and imperative surgery tend to be associated with
      renal infarction, although it does not affect GFR. (2) Renal artery
      reconstruction was highly successful in preserving renal mass (or normal cortical
      image), albeit longer ischemic time than simple ligation. (3) Considering
      importance of preserved nephron mass in clinical renal transplantation every
      attempt should be made to repair the donor arterial anomalies when expected
      (elective) or found (imperative). (4) Thorough preoperative evaluation of donor
      renal arteries is mandatory.

PMID- 9184452
TI  - [A case of porocarcinoma arising on the penile shaft].
AB  - BACKGROUND: Porocarcinoma is a rare eccrine sweat gland tumor, and a varied
      treatment is not yet determined for metastatic disease because of the chemo
      resistant and radio-resistant nature of this tumor. CASE: This report describes a
      case of porocarcinoma arising on the penile shaft of 83-year-old man with
      extensive lymph node metastases. He was treated with emasculation and bilateral
      ilio-inguinal lymph node dissection. Histological examination of the resected
      tumor showed a homogeneous round cells with duct-like formation in some part and
      Pagetoid infiltration was also noted in the dermis. Immunohistochemical
      examination demonstrated a positive CEA and negative S-100 staining and this
      result was consistent with the pathological diagnosis of porocarcinoma. One
      course of chemotherapy which consisted of methotrexate, cisplatin, adriamycin,
      and bleomycin was given to the patient following surgery for the treatment of
      residual lymph nodes in the paraaortic area. Abdominal CT scan revealed partial
      response, about -94% shrinkage, after one course of chemotherapy. The duration of
      the response lasted four 4 months. He died of pneumonia caused by MRSA after 4
      months and the autopsy revealed multiple liver metastases and a massive
      infiltration of tumor cells in the bone marrow of lumbar vertebra. CONCLUSIONS:
      There is no definite treatment modality available for metastatic porocarcinoma.
      Because of the patient's age, only one course of chemotherapy was given, however,
      a fairly good response against this rare tumor suggested that this new regimen
      might be effective against porocarcinoma.

PMID- 9184453
TI  - [Postprostatectomy dysuria: restored voiding function by perineal hot water spray
      in an old male with a contractile bladder].
AB  - The hot water spray on perineum restored voiding function in a 77-year-old male
      patient with the poorly contractile bladder. He noticed the gradual decrease of
      bladder sensation and voiding stream, and needed clean intermittent
      catheterization to empty bladder even after TUR-P. Neurological examination
      revealed only weakened anal and bulbocavernosus reflex and impaired skin
      sensation of foot plate and perineum. Simple cystometry showed impaired
      perception of bladder filling and underactive bladder. Electromyography of the
      pelvic floor displayed decreased responses to bladder filling and voluntary
      sphincter contraction. Spine-X-ray examination and computed tomography of brain
      and spinal cord did not reveal any neurological lesions except for the silent
      small infarction of subcortex. Trial of drug therapy with Distigmine bromide,
      Cernilton and Prazosin did not restore voiding function. By accident, however,
      patient himself found spontaneous voiding could be induced by hot water spray on
      perineum and/or scrotum during bidet using. Since then, he has been continuing
      this stimulation daily for 4 years, with which almost complete voiding is
      possible without catheterization, though bladder sensation remains impaired. The
      pathophysiology and affecting factors on micturition reflex in this case were
      discussed.

PMID- 9184454
TI  - Technological aspects of minimal access surgery.
AB  - Minimal access surgery (MAS) is bringing about a revolution in surgical practice
      with certain operations being almost wholly carried out using MAS techniques in
      some countries. This paper describes the development, current status and future
      prospects of MAS from a technological perspective.

PMID- 9184455
TI  - An automated method for assessing routine radiographs of patients with total hip
      replacements.
AB  - This paper describes a new, fully automated method of locating objects on
      radiographs of patients with total joint replacements (TJRs). A statistical
      computer model, known as an active shape model, was trained to identify the
      position of the femur, pelvis, stem and cup marker wire on radiographs of
      patients with Charnley total hip prostheses. Once trained, the model was able to
      locate these objects through a process of automatic image searching, despite
      their appearance depending on the orientation and anatomy of the patient.
      Experiments were carried out to test the accuracy with which the model was able
      to fit to previously unseen data and with which reference points could be
      calculated from the model points. The model was able to locate the femur and stem
      with a mean error of approximately 0.8 mm and a 95 per cent confidence limit of
      1.7 mm. Once the model had successfully located these objects, the midpoint of
      the stem head could be calculated with a mean error of approximately 0.2 mm.
      Although the model has been trained on Charnley total hip replacements, the
      method is generic and so can be applied to radiographs of patients with any TJR.
      This paper shows that computer models can form the basis of a quick, automatic
      method of taking measurements from standard clinical radiographs.

PMID- 9184456
TI  - A technique for measuring the compressive modulus of articular cartilage under
      physiological loading rates with preliminary results.
AB  - This paper describes a technique and apparatus for measuring the compressive
      modulus of articular cartilage under physiological loading rates. The compressive
      modulus is the most relevant property to the primary function of articular
      cartilage i.e., load carriage. It has been determined previously from measurement
      of cartilage deformation under slow or almost static loading conditions. The
      modulus was based on deformations occurring 2 s after the initial application of
      load which greatly reduces its relevance since in physiological conditions joint
      loading occurs within 10-150 ms. Five human knee joints have been used to test
      the apparatus before a major study is undertaken. The preliminary results from
      these joints show that the compressive modulus of articular cartilage measured
      within physiological loading time intervals was much greater than previously
      reported. The compressive modulus at 20 ms was in the range 4.4-27 MPa and was
      between 32 and 75 per cent greater than its value obtained at 2 s after loading.

PMID- 9184457
TI  - Stump-socket interface pressure as an aid to socket design in prostheses for
      trans-femoral amputees--a preliminary study.
AB  - A system for measuring the stump-socket interface pressure was designed and built
      using a strain gauged type load cell. The system was utilized to study the
      pressure distribution in the quadrilateral and ischial containment type sockets.
      Two volunteer trans-femoral amputees fitted with both types of socket
      participated in the experiments. Pressures were measured while the subjects were
      standing and during walking. The maximum pressure recorded for standing was 34
      kPa and for walking 95 kPa. Comparison made between the two sockets indicated
      that higher pressures were recorded at the proximal brim of the quadrilateral
      socket whereas the ischial containment socket produces a more evenly distributed
      pressure profile. The pressure distribution on the medial and lateral walls of
      both types of socket were similar but in the anterior and posterior walls,
      significant differences were noted. The results obtained from this study were
      compared with those found in published literature and the biomechanics of the two
      types of socket is discussed.

PMID- 9184458
TI  - The influence of the stem-cement interface in total hip replacement--a comparison
      of experimental and finite element approaches.
AB  - Experimental and finite element investigations were carried out on axisymmetric
      models of the femoral component of a total hip replacement. In one instance, the
      interface between the stem and the surrounding bone cement was assumed to be
      rigidly bonded; in a second, it was allowed to slip. For the latter case, a
      friction coefficient of 0.2 was determined experimentally. The predictions of the
      finite element models demonstrated excellent agreement with the results from the
      experimental tests at all sites where comparisons were made, thus validating
      these models. The effect of stem-cement slip was shown to reduce the maximum
      shear stress in the cement mantle by approximately 30 per cent.

PMID- 9184459
TI  - Biological reaction to debris in relation to joint prostheses.
AB  - Bone loss induced by the inflammatory response to wear particles is a major cause
      of long-term failure of total joint replacement. This review describes the
      cellular reaction occurring in response to these particles and what is currently
      known about the inflammatory mechanisms contributing to bone resorption.

PMID- 9184460
TI  - On an ambulance stretcher suspension concerned with the reduction of patient's
      blood pressure variation.
AB  - The design process and control of an ambulance stretcher suspension to reduce
      patient's blood pressure variation (BPV) is discussed. The BPV caused by applying
      the vehicle brakes may lead to deterioration of a patient's condition. The
      proposed method can reduce BPV by tilting the stretcher and counterbalancing back
      to-front acceleration of the ambulance with gravity. The experimental results
      obtained when using a manually controlled stretcher confirm that BPV is reduced
      by tilting the stretcher. A continuous control method that varies the tilting
      angle is investigated through simulation analysis. The results show that this
      control method reduces the BPV effectively and achieves safe transport of the
      patient.

PMID- 9184461
TI  - A comparison of finite element codes for the solution of biphasic poroelastic
      problems.

PMID- 9184462
TI  - Current approaches to identifying the severely mentally ill.
AB  - Mental health care is expensive to provide and resources should be targeted.
      Possible approaches to such a prioritization are outlined. In the United Kingdom,
      care is to be provided on the basis of need. The key issue is then identifying
      the severely mentally ill, who are most in need of mental health care.
      Definitions of severe mental illness used in research studies are reviewed,
      indicating a lack of consensus about identifying this group. Current practice in
      England was surveyed, by obtaining written documentation from 20 agencies on the
      eligibility criteria they use for deciding whether someone should receive mental
      health care. Government departments, user groups and professional bodies were
      also surveyed. The findings indicate that definitions of severe mental illness
      use the five dimensions of safety, informal and formal support, diagnosis,
      disability and duration--the SIDDD dimensions. These dimensions offer a framework
      for developing definitions of severe mental illness at the local level, thereby
      identifying the priority group for mental health care.

PMID- 9184463
TI  - Behaviors as risk factors for rehospitalization: implications for predicting and
      preventing admissions among the seriously mentally ill.
AB  - This case-control study investigated the extent to which aberrant behaviors, in
      contrast to more traditional clinical factors (such as symptoms and alcohol
      abuse), place individuals with schizophrenia at increased risk for
      rehospitalization. One hundred and one recidivists (cases) were matched to 101
      non-recidivists (controls) on gender, race, and time since index hospitalization.
      Key informants, usually family members, were interviewed to assess behaviors
      during a 2-week period. After controlling for possible confounding variables, we
      found that each aberrant behavior increased the risk for rehospitalization, but
      highly disruptive or dangerous behaviors (such as threatening others, acting very
      bizarrely, or attempting suicide) conveyed a markedly high degree of risk
      (adjusted odds ratio = 83.9). It is possible that service providers may be able
      to avert the fiscal and emotional cost of hospitalization by collaborating more
      closely with family members to identify these behaviors and intervene before
      hospitalization becomes unavoidable.

PMID- 9184465
TI  - The costs and benefits of boundary maintenance: stress, religion and culture
      among Jews in Britain.
AB  - This paper examines stress among two groups of orthodox Jews suggested to differ
      in the strength of the boundary of their religious group. Comparisons were made
      between the two groups, and with urban and rural groups studied by other
      researchers. Proportions of boundary-maintenance events (events whose threat had
      been caused or exacerbated by Jewishness) and of severe events, and proportions
      and rates of regular, irregular and disruptive events were examined. Boundary
      maintenance events were higher among the more religiously orthodox affiliated
      group, and among whom religious observance was indeed reported to be higher. It
      was suggested that conditions of higher boundary maintenance would be associated
      with higher rates and proportions of regular events and with lower rates and
      proportions of irregular and disruptive events. Generally, the analyses supported
      this expectation. Boundary-maintenance events themselves were somewhat less
      severe, though not less likely to be irregular or disruptive than other events.
      Depression was shown to be unrelated to boundary-maintenance events and
      (surprisingly) unrelated to contextual threat when the effects of irregularity
      disruption were controlled. Depression was, however, strongly related to
      irregular and disruptive events. The results are compared with those of related
      work, and suggest that the general lowering effect of affiliation to a religious
      group may be partly explained by the effects of boundary maintenance, which
      involves stress, but of a less depressogenic kind than the disruptive stress
      associated with conditions of low/no boundary maintenance. The findings have
      implications for understanding the relations between culture and mental disorder.

PMID- 9184464
TI  - Reliability of the recording of schizophrenia and depressive disorder in the
      Saskatchewan health care datafiles.
AB  - Administrative data have long been used in psychiatric epidemiology and outcomes
      evaluation. This article examines the reliability of the recording of
      schizophrenia and depressive disorder in three Saskatchewan administrative health
      care utilization datafiles. Due to their comprehensive nature, these datafiles
      have been used in a wide range of epidemiologic studies. Close agreement was
      found between hospital computer data and patients' charts for personal and
      demographic factors (> or = 94.7%). Diagnostic concordance between computerized
      hospital data and medical charts was very good for schizophrenia (94%) but poor
      for depressive disorder (58%). Appropriate physician services were identified for
      60% and 72% of hospital discharges for schizophrenia and depressive disorder,
      respectively, and exact diagnostic agreement between hospital and physician
      datafiles was 62% for schizophrenia and 66% for depressive disorder. Appropriate
      provincial mental health branch services were found for 83% and 38% of hospital
      discharges for schizophrenia and depressive disorder, respectively; exact
      diagnostic concordance between these datafiles was 75% for schizophrenia and 0%
      for depressive disorder. A significant number of patients with major or neurotic
      depression appeared to be wrongly coded as having depressive disorder in the
      hospital file. The differences in diagnostic agreement may also be partly a
      function of how the two conditions are differentially treated in the health
      system. These findings suggest that more specific and severe psychiatric
      diagnoses are likely to be recorded accurately and consistently in the
      Saskatchewan datafiles. However, disorders with multiple manifestations or those
      for which there are several possible codes should be examined with caution and
      ways sought to validate them. Attention should also be paid to which service
      sectors are involved in the treatment of specific disorders.

PMID- 9184466
TI  - The Mannheim interview on social support psychometric characteristics of a
      Spanish version.
AB  - This study analysed the psychometric characteristics of a Spanish version of the
      Mannheim Interview on Social Support (MISS) with 82 mental health care centre
      outpatients. Moderate and high correlation coefficients were obtained on test
      retest reliability for a 6 week interval. In addition, correlations with the
      Revised UCLA Loneliness Scale and the Perceived Social Support scale confirmed an
      acceptable concurrent validity.

PMID- 9184467
TI  - Experiences of religious healing in psychiatric patients in south India.
AB  - A survey was carried out over a 3-month period to determine experiences of
      religious healing in a group of 198 consecutive psychiatric patients attending a
      hospital in Tamil Nadu, South India. Of these, 89 (45%) had sought between 1 and
      15 sessions from either Hindu, Muslim of Christian healers. The number of
      patients visiting healers was linked significantly with their income, while a
      significantly higher number under the age of 17 years had received such help
      compared with older age groups. A significantly higher consultation rate was
      observed in those patients with schizophrenia and delusional disorders when
      compared with other mental illness. An average of 30% of patients claimed some
      benefit from healer consultation, although the majority (91%) had discontinued
      such treatment at the time of the hospital attendance. The role of social
      support, methods of traditional healing and the underlying implications for
      service delivery are discussed. The implications for service providers to ethnic
      minorities need to be taken into account while planning services.

PMID- 9184468
TI  - Mental disorders and health care seeking in Bandiagara: a community survey in the
      Dogon Plateau.
AB  - A two-level community study was carried out among the Peul and Dogon populations
      of the Bandiagara plateau (Mali). For the purpose of the study the Questionnaire
      pour le depistage en sante mentale (QDSM), a 23-item screening questionnaire
      derived from the Self-Reporting Questionnaire (SRQ), was adapted and validated;
      internal consistency and accuracy were evaluated. In the first phase of the
      study, 466 subjects randomly selected on a residential basis were evaluated by
      means of the QDSM. In the second phase all subjects who were "positive" at the
      screening, as well as a sample who were "negative", were examined by means of a
      semistructured interview. When necessary, clinical and laboratory investigations
      were performed. The estimated prevalence of psychiatric cases was 6.4%. A
      significant risk was associated with age and education. Somatic diseases
      frequently associated with psychiatric disorders were genitourinary tract
      disorders, tuberculosis and disabling cardiopathies. The main factor determining
      the seeking of medical help either through traditional of conventional health
      systems was the presence of a somatic disorder. The presence of a true minor
      psychiatric disorder, however, was often associated with divining practices.

PMID- 9184469
TI  - Assessing rearing behaviour from the perspectives of the parents: a new form of
      the EMBU.
AB  - The EMBU (Egna Minnen Betraffande Uppfostran) is a self-reporting questionnaire
      developed to assess memories of adults about their parents' rearing practices. In
      the present study, an exploratory factor analysis was carried out on items of the
      EMBU-P, a new version of the EMBU especially designed to obtain ratings from
      parents about their own rearing behaviour with their children. The factor
      analysis yielded a structure similar to that obtained with the original EMBU
      (Rejection, Emotional Warmth, Control Attempts and Favouring Subject), but
      composed of fewer items. The internal consistency was adequate for the three
      major scales. Some significant correlations emerged between the EMBU-P scales.
      The Rejection scale correlated negatively with the Emotional Warmth scale and
      positively with the Control Attempts scale. The latter also correlated positively
      with Emotional Warmth. There were no significant correlations between the scales
      and the age of the parents. The sex of the parents was significantly associated
      with the EMBU-P scores.

PMID- 9184470
TI  - A diagnostic comparison of homeless and nonhomeless patients in an urban mental
      health clinic.
AB  - This study compared demographic and diagnostic characteristics of a sample of
      homeless outpatient mental health clinic attenders with a domiciled comparison
      group from the same clinic. Data on demographic variables and DSM-III-R
      psychiatric diagnoses were collected over a two-year period on a consecutive
      sample of 166 homeless and 117 nonhomeless clinic attenders. Data on demographics
      and psychiatric diagnoses of the homeless clinic attenders were further compared
      with data collected systematically from 900 homeless individuals in the same
      city. In the clinic, homeless subjects were more often members of ethnic
      minorities, and homeless women were significantly younger and better educated
      than their nonhomeless counterparts. Rates of schizophrenia, bipolar disorder,
      and somatization disorder were not significantly different between homeless and
      nonhomeless groups. Major depression was about four times as prevalent in
      nonhomeless men as in homeless men. Homeless men were significantly more likely
      than nonhomeless men to qualify for a diagnosis of alcohol use disorder, and
      homeless women were more likely than other women to qualify for a diagnosis of
      drug use disorder. Both homeless men and women were significantly more likely
      than their domiciled counterparts to meet criteria for antisocial personality
      disorder. Personality disorder other than antisocial was more prevalent in
      nonhomeless men than in homeless men. Combined rates of personality disorder were
      significantly higher among homeless than nonhomeless women, but not men. Homeless
      clinic attenders were demographically and diagnostically very similar to a
      general homeless population in the same city. The only diagnosis that was more
      prevalent in the homeless clinic than in the homeless community was antisocial
      personality disorder. We concluded that because of difference in diagnostic
      prevalence, homeless and nonhomeless individuals in mental health clinics need to
      be considered independently. Clinicians treating homeless outpatients may benefit
      from having special facility in diagnosis and management of antisocial
      personality disorder and substance abuse, along with expertise in other
      psychiatric disorders in this population.

PMID- 9184471
TI  - Ionotropic glutamate receptors: new types and new concepts.

PMID- 9184472
TI  - More on the classification of cysteinyl leukotriene receptors.

PMID- 9184474
TI  - Bristol-Myers Squibb Unrestricted Biomedical Research Grants Programme.

PMID- 9184473
TI  - The interaction between salmeterol and the beta 2-adrenoceptor protein.

PMID- 9184475
TI  - What is pharmacology? A discussion.

PMID- 9184476
TI  - Parkinson's disease: prospects for improved drug therapy.
AB  - L-Dopa has long been the mainstay of therapy for Parkinson's disease but its long
      term shortcomings, principally uncoordinated, spasmodic or irregular movements
      (dyskinesias) and fluctuating control of motor symptoms (on/off fluctuations),
      are well documented. The postulated neuroprotective properties of L-deprenyl,
      often used as an adjunct to L-dopa, are under scrutiny and doubts have also been
      raised regarding its safety. Alternative therapeutic approaches are clearly
      needed. In this review, Jim Hagan, Derek Middlemiss, Paul Sharpe and George Poste
      outline some new approaches to treatment, with an emphasis on novel, selective
      dopamine receptor agonists. In addition, Parkinson's disease is commonly thought
      to be caused by the neurotoxic effects of an unidentified agent but recent data
      indicate a greater genetic component than previously recognized. Developments in
      the genetics of Parkinson's disease may provide the key to the next generation of
      therapeutics.

PMID- 9184477
TI  - Phosphodiesterase (PDE)4 inhibitors: anti-inflammatory drugs of the future?
AB  - Phosphodiesterase type 4 (PDE4) plays a major role in modulating the activity of
      virtually all cells involved in the inflammatory process. Inhibitors of this
      enzyme family display impressive anti-inflammatory and disease-modifying effects
      in a variety of experimental models. In this review, Mauro Teixeira, Robert
      Gristwood, Nicola Cooper and Paul Hellewell examine the capacity of PDE4
      inhibitors to exert anti-inflammatory actions in vivo and discuss the potential
      of this class of drugs to take their place as novel therapeutic agents for a
      variety of inflammatory diseases.

PMID- 9184478
TI  - Inducible receptors.
AB  - While regulation of receptor function is known to occur at many levels (e.g.
      transcriptional, post-translational), it is generally perceived that a tissue
      either expresses or does not express a particular receptor in an all-or-none
      fashion. Many pathological (e.g. tissue injury) and physiological (e.g.
      angiogenesis) processes have, however, been shown to be associated with the
      transcriptional induction of specific receptors. Induced receptors are not
      confined to any particular class, but range from G protein-coupled receptors to
      receptor tyrosine kinases. The potential implications of de novo receptor
      expression are profound with respect to potential novel therapeutic targets in
      specific disease states. Further, this observation may explain unexpected side
      effects in the pharmacotherapy of existing disease states. In this article Lucy
      Donaldson, Michael Hanley and Amparo Villablanca discuss circumstances under
      which de novo receptor induction has been described, potential mechanisms of
      induction and the implications for pharmacology.

PMID- 9184479
TI  - Brain potentials reflect violations of gender stereotypes.
AB  - Event-related brain potentials (ERPs) were recorded while 14 males and 14 females
      read sentences containing a reflexive pronoun that referred to a definitionally
      or stereotypically male or female antecedent noun. Pronouns that disagreed with
      the gender definition or gender stereotype of the antecedent elicited a large
      amplitude positive wave. Violations of gender definitions elicited a larger
      positive wave than did violations of gender stereotypes. Furthermore, the
      positive wave elicited by stereotype violations persisted even when subjects
      judged these sentences to be acceptable. Finally, female subjects exhibited
      larger positivities than did male subjects, regardless of whether the gender
      mismatch involved a definitional or stereotypical antecedent. These results are
      taken to indicate that ERPs are sensitive to violations of gender-based
      occupational stereotypes and that the ERP response to stereotype violations is
      similar to the P600 effect elicited by a variety of syntactic anomalies.

PMID- 9184480
TI  - Inhibitory control over no-longer-relevant information: adult age differences.
AB  - Hartmann and Hasher (1991) used a garden-path task in which younger and older
      adults generated the final word for each of a series of high-cloze sentences.
      Under instructions to remember the final word, the experiment included critical
      sentences for which the generated word was replaced by a new, to-be-remembered
      target. Using an implicit priming task, the first experiment replicated a basic
      finding: Younger adults showed priming only for the target words, whereas older
      adults showed priming for both the generated and target words. Two experiments
      explored the boundary conditions. One showed that an additional sentence that
      interpreted the new target word enabled older adults to narrow access to only the
      target word. The provision of additional time following the introduction of the
      new target word did not. Specific information, not more time, is required for
      inefficient inhibitory mechanisms to clear the recent past from memory.

PMID- 9184481
TI  - First categorization of stimuli with multivalued dimensions.
AB  - The extended generalized context model's (EGCM's) ability to account for the time
      course of categorization of stimuli with multivalued dimensions was tested in two
      experiments. In each experiment, the participants were first trained to classify
      stimuli (semicircles of variable size with a radial line of variable orientation)
      into two categories. In the subsequent transfer stage, they categorized a set of
      transfer stimuli. The time available on each transfer trial was manipulated.
      Response had to be given within 400 msec, within 700 msec, or without time
      pressure. Different category structures were used in Experiments 1 and 2. The
      results of both experiments showed reliable effects of response deadline. The
      EGCM accounted for the data and performed consistently better than an alternative
      model.

PMID- 9184482
TI  - The effect of presemantic acoustic adaptation on semantic "satiation".
AB  - A decrement in the strength of the meaning of a word after rapid repetition of
      that word has been called "semantic satiation." This study asked whether this
      "satiation" might be produced by presemantic acoustic adaptation. Category words
      were utilized to prime the meaning of target words. The adaptation or "satiation"
      procedure, 30 rapid repetitions of the primes, was compared with a control
      condition of 3 repetitions. Participants listened to a series of prime words,
      each repeated by either the same speaker or many speakers, and then made semantic
      decisions on target words. When all the repetitions of a prime word are produced
      by the same speaker, presemantic and semantic repetitions are confounded. When
      the repetitions are produced by different speakers, presemantic acoustic
      repetition is abolished. A semantic decrement was detected with single-speaker,
      but not with multiple-speaker, repetitions of prime words. This study concluded
      that the semantic "satiation" observed here was a decrement in the activation
      level of semantic representations induced by presemantic acoustic adaptation.

PMID- 9184483
TI  - A visuospatial "phonological loop" in working memory: evidence from American Sign
      Language.
AB  - In two experiments, the question of whether working memory could support an
      articulatory rehearsal loop in the visuospatial domain was investigated. Deaf
      subjects fluent in American Sign Language (ASL) were tested on immediate serial
      recall. In Experiment 1, with ASL stimuli, evidence was found for manual motoric
      coding (worse recall under articulatory suppression) and previous findings of ASL
      based phonological coding (worse recall for phonologically similar lists) were
      replicated [corrected]. The two effects did not interact, suggesting separate
      components which both contribute to performance. Stimuli in Experiment 2 were
      namable pictures, which had to be recoded for ASL-based rehearsal to occur. Under
      these conditions, articulatory suppression eliminated the phonological similarity
      effect. Thus, an articulatory process seems to be used in translating pictures
      into a phonological code for memory maintenance. These results indicate a
      configuration of components similar to the phonological loop for speech,
      suggesting that working memory can develop a language-based rehearsal loop in the
      visuospatial modality.

PMID- 9184484
TI  - Mental animation in the visuospatial sketchpad: evidence from dual-task studies.
AB  - We used the dual-task paradigm to provide evidence that inferring the motion of a
      component of a mechanical system (mental animation) is a spatial visualization
      process. In two experiments, participants were asked to solve mental animation
      problems while simultaneously retaining either a visuospatial working memory load
      (a configuration of dots in a grid) or a verbal memory load (a list of letters).
      Both experiments showed that mental animation interferes more with memory for a
      concurrent visuospatial load than with memory for a verbal load. Experiment 1
      also showed that a visuospatial working memory load interferes more with mental
      animation than does a verbal memory load. Furthermore, Experiment 2 showed that
      mental animation interferes more with a visuospatial memory load than does a
      verbal reasoning task that takes approximately the same amount of time.

PMID- 9184485
TI  - Strategic reliance on phonological mediation in lexical access.
AB  - The present study investigated strategic variation in reliance on phonological
      mediation in visual word recognition. In Experiment 1, semantically related or
      unrelated word primes preceded word, pseudohomophone (e.g., trane), or
      nonpseudohomophone (e.g., trank) targets in a lexical decision task. Semantic
      priming effects were found for words, and response latencies to pseudohomophones
      were longer in related than in unrelated prime conditions. In Experiment 2,
      related or unrelated word primes preceded word or pseudohomophone targets. A
      relatedness effect was found for words, although it was significant at a 600-msec
      prime-target stimulus onset asynchrony (SOA) and not at a 200-msec SOA. There was
      no relatedness effect for pseudohomophones. Experiment 3 was a replication of
      Experiment 2, except that pseudohomophones were replaced by nonpseudohomophonic
      orthographic controls. Facilitation effects for related target words were greater
      in Experiment 3 than in Experiment 2. The results reflect apparent variations in
      the expectation that a related prime reliably indicates that a target is a word.
      Although reliance on phonological mediation might be strategically contingent,
      there could be a brief time period in which phonologically mediated lexical
      access occurs automatically. Whether phonological information is maintained or
      suppressed subsequently depends on its overall usefulness for the task.

PMID- 9184486
TI  - Modeling the conscious correlates of recognition memory: reflections on the
      remember-know paradigm.
AB  - Understanding how memory processes contribute to the conscious experience of
      memory is central to contemporary cognitive psychology. Recently, many
      investigators (e.g., Gardiner, 1988) have examined the remember-know paradigm to
      understand the conscious correlates of recognition memory. A variety of studies
      have demonstrated that variables have different effects on remember and know
      responses, and these findings have been interpreted in the context of dual
      process models of recognition memory. This paper presents a single-process model
      of the remember-know paradigm, emphasizing the dependence of remember and know
      judgments on a set of common underlying processes (e.g., criterion setting). We
      use this model to demonstrate how a single-process model can give rise to the
      functional dissociations presented in the remember-know literature. We close by
      detailing procedures for testing our model and describing how those tests may
      facilitate the development of dual-process models.

PMID- 9184487
TI  - Explicit contamination in "implicit" memory for new associations.
AB  - In one view of implicit memory, priming arises from modification of preexisting
      representations; however, the role of such representations is currently in doubt
      following findings of implicit memory for newly formed associations. Closer
      consideration of studies reporting this effect, and of others that have failed to
      obtain it, suggests that such priming might results from the employment of
      explicit memory strategies. With measures designed to permit exclusion of such
      strategies, three experiments using lexical decision and stem-completion tasks
      found no evidence of truly implicit memory for unrelated pairs. Instead, priming
      was found only in those subjects (50% of the total in one experiment) who
      reported using explicit memory in stem completion. Contrary to previous
      conclusions, the results indicate a role for established representations in
      explaining implicit memory.

PMID- 9184488
TI  - A mere exposure effect for transformed three-dimensional objects: effects of
      reflection, size, or color changes on affect and recognition.
AB  - If the mere exposure effect is based on implicit memory, recognition and affect
      judgments should be dissociated by experimental variables in the same manner as
      other explicit and implicit measures. Consistent with results from recognition
      and picture naming or object decision priming tasks (e.g., Biederman & E.E.
      Cooper, 1991, 1992; L.A. Cooper, Schacter, Ballesteros, & Moore, 1992), the
      present research showed that recognition memory but not affective preference was
      impaired by reflection or size transformations of three-dimensional objects
      between study and test. Stimulus color transformations had no effect on either
      measure. These results indicate that representations that support recognition
      memory code spatial information about an object's left-right orientation and
      size, whereas representations that underlie affective preference do not.
      Insensitivity to surface feature changes that do not alter object form appears to
      be a general characteristic of implicit memory measures, including the affective
      preference task.

PMID- 9184489
TI  - The effects of cue distinctiveness on odor-based context-dependent memory.
AB  - The distinctiveness of an ambient odor was examined in relation to its success as
      a cue in context-dependent memory. Distinctiveness was examined in terms of both
      cue novelty and contextual appropriateness. Two experiments were conducted in
      which three different ambient odors that varied in familiarity and contextual
      appropriateness were manipulated at an incidental word learning encoding session
      and at a free recall retrieval session 48 h later. Experiment 1 revealed that
      when a novel ambient odor (osmanthus) was the available context cue, word recall
      was better than in any other condition. Further, among familiar odor cues, recall
      was better with a contextually inappropriate odor (peppermint) than with a
      contextually appropriate odor (clean fresh pine). Experiment 2 confirmed that
      superior word recall with osmanthus and peppermint depended on the odor cue's
      being available at both encoding and retrieval, and that the relation of an odor
      to the situational context is a key factor for predicting its effectiveness as a
      retrieval cue.

PMID- 9184490
TI  - Prior experience and complex procedures.
AB  - The role of prior knowledge in learning complex procedures was investigated in a
      transfer task in which subjects learned two related procedures in sequence. In
      Experiment 1, we manipulated the conceptual and structural similarity between the
      two procedures; in Experiment 2, we manipulated whether the order of the steps
      within subprocedures was the same or different during training and transfer, or
      whether the order of the subprocedures was the same or different. The results
      lead us to hypothesize that transfer in complex procedures is mediated primarily
      by a memory for specific steps rather than by conceptual understanding or problem
      solving. In particular, we were able to model the results precisely on the
      assumption that subjects use superficial similarity to retrieve the sequences of
      steps needed to perform segments of the procedure.

PMID- 9184491
TI  - Characterizing the intuitive representation in problem solving: evidence from
      evaluating mathematical strategies.
AB  - Two experiments were conducted to investigate the nature of the intuitive problem
      representation used in evaluating mathematical strategies. The first experiment
      tested between two representations: a representation composed of principles and
      an integrated representation. Subjects judged the correctness of unseen math
      strategies based only on the answers they produced for a set of temperature
      mixture problems. The distance of the given answers from the correct answers and
      whether the answers violated one of the principles of temperature mixture were
      manipulated. The results supported the principle representation hypothesis. In
      the second experiment we manipulated subjects' understanding of an acid mixture
      task with a brief paragraph of instruction on one of the principles. Subjects
      then completed an estimation task intended to measure their understanding of the
      problem domain. The evaluation task from the first experiment was then presented,
      but with acid mixture instead of temperature mixture. The results showed that
      intuitive understanding of the domain mediates the effect of instruction on
      evaluating problems. Additionally, the results supported the hypothesis that
      subjects perform a mapping process between their intuitive understanding and math
      strategies.

PMID- 9184492
TI  - Causal and conditional inferences: a comment on Cummins (1995)
AB  - Cummins (1995) offers an analysis of causal and truth-functional sufficiency and
      necessity to predict and explain the effects on conditional inferences of two
      pragmatic factors: alternative causes and disabling conditions. However, the
      justification of these predictions is inconsistent. This note offers a modified
      analysis which puts her predictions on a sounder base: it is proposed that
      alternative causes and disabling conditions affect judgments of argument validity
      under three different models for the causal conditional.

PMID- 9184493
TI  - Region of birth and mortality among black Americans.

PMID- 9184494
TI  - The uses of psychosocial epidemiology in promoting refugee health.

PMID- 9184495
TI  - Race, ethnicity, and health outcomes--unraveling the mediating role of
      socioeconomic status.

PMID- 9184496
TI  - Environmental racism and public health.

PMID- 9184497
TI  - Topics for our times: affirmative action and women's health.

PMID- 9184498
TI  - Policy research for disease prevention: challenges and practical recommendations.
AB  - Policy approaches to health promotion and disease prevention hold great
      potential, as several community-based projects have illustrated. Policy
      interventions, despite their wide-spread use, frequently lack a systematic
      framework for implementation and evaluation. The authors propose a four-stage
      framework for the formation and evaluation of public health policy. The stages
      are identification of health risks and preventive options; intervention
      development; policy development; and policy enactment and assurance. A strong
      focus on evaluation is included within the framework. In addition, a series of
      practical implications and recommendations are given under the broad headings of
      evaluation issues and linkages. It is hoped that the issues described will lead
      to more systematic implementation and evaluation of public health policy
      measures.

PMID- 9184499
TI  - US trends in nutrient intake: the 1987 and 1992 National Health Interview
      Surveys.
AB  - OBJECTIVES: This study examined US trends in nutrient intake, using almost
      identical methods and nutrient databases in two time periods. METHODS: An
      extensive dietary intake questionnaire was included in supplements to the 1987
      and 1992 National Health Interview Surveys. Dietary data from approximately
      11,000 persons in each of those years were analyzed. RESULTS: The total and
      saturated fat intake and the percentage of energy from fat declined among Whites
      and Hispanics, but only minimal changes were seen in Black Americans. The changes
      in fat intake were attributable principally to behavioral changes in frequency
      and type of fat-containing foods consumed rather than to the increased
      availability of leaner cuts of meat. Dietary cholesterol showed one of the
      largest declines of the nutrients examined. Less desirable changes were also
      seen. Cereal fortification played an important role in the observed changes in
      several micronutrients. CONCLUSIONS: Educational campaigns on dietary fat and
      cholesterol have been moderately effective, but not in all racial/ethnic groups.
      Future campaigns should emphasize maintaining or increasing micronutrient intake.

PMID- 9184500
TI  - Stable behaviors associated with adults' 10-year change in body mass index and
      likelihood of gain at the waist.
AB  - OBJECTIVES: The purpose of this study was to identify behaviors associated with
      change in body mass index or with weight gain at the waist. METHODS: A cohort of
      79236 White, non-Hispanic, healthy adults was questioned in 1982 and 1992 about
      diet and 10 physical activities. Estimates were made of the mean effects of
      stable behaviors on 10-year change in body mass index and on odds ratios for gain
      at the waist. RESULTS: Ten-year changes in body mass index was associated
      positively with meat consumption and smoking cessation and inversely with
      vegetable consumption, vitamin E supplementation, continued smoking, and some
      vigorous activities (e.g., jogging/running). Women's body mass index decreased
      with walking 4 or more hours per week and with regular alcohol intake, but these
      behaviors had a smaller effect on men's body mass index. weight gain was
      inversely associated with high vegetable consumption, walking 4 or more hours per
      week, and jogging/running 1 to 3 hours per week but not with less demanding
      physical activities. CONCLUSIONS: Simple derivation of behaviors associated with
      weight loss or reduced abdominal obesity may enhance programs designed to prevent
      obesity and chronic diseases.

PMID- 9184501
TI  - Do smokers understand the mortality effects of smoking? Evidence from the Health
      and Retirement Survey.
AB  - OBJECTIVES: This study examined whether smokers recognize that smoking is likely
      to shorten their lives and, if so, whether they understand the magnitude of this
      effect. METHODS: People's expectations about their chances of reaching age 75
      were compared with epidemiological predictions from life tables for never,
      former, current light, and current heavy smokers. Data on expectations of
      reaching age 75 came from the Health and Retirement Survey, a national
      probability sample of adults aged 50 through 62 years. Predictions came from
      smoking-specific life tables constituted from the 1986 National Mortality
      Followback Survey and the 1985 and 1987 National Health Interview Surveys.
      RESULTS: Among men and women, the survival expectations of never, former, and
      current light smokers were close to actual predictions. However, among current
      heavy smokers, expectations of reaching age 75 were nearly twice as high as
      actuarial predictions. CONCLUSIONS: These findings suggest that at least heavy
      smokers significantly underestimate their risk of premature mortality.

PMID- 9184502
TI  - Alcohol, tobacco, and other drug use among rural/small town and urban youth: a
      secondary analysis of the monitoring the future data set.
AB  - OBJECTIVES: This study compared prevalence of substance use among high school
      seniors in rural and urban areas from 1976 through 1992. METHODS: We used data
      collected for these years from urban (n = 75,916) and rural (n = 51,182) high
      school seniors. Thirty-day prevalence for alcohol, cigarettes, marijuana,
      cocaine, LSD, and inhalant use, binge drinking, smoking a pack or more of
      cigarettes a day, and daily alcohol and marijuana use were evaluated. RESULTS:
      Substance use declined from 1976 through 1992. In 1976, urban students had
      greater prevalence for most substances, but by 1992, rural and urban students
      were similar, with rural students having higher prevalence for alcohol and
      cigarette use (particularly excessive use). Trends were similar for both sexes,
      though rural girls showed a later catch-up to use levels of urban girls.
      CONCLUSIONS: Rural students are currently at risk approximately equal to that of
      urban students. Other studies have demonstrated the association of substance use
      with increased morbidity and mortality. Policy alterations and health education
      programs should address this pattern in the nation's rural areas.

PMID- 9184503
TI  - Childhood abuse and the use of inhalants: differences by degree of use.
AB  - OBJECTIVES: Using two existing ethnographic studies of drug-involved adults, this
      study evaluates the association between child-abuse victimization and levels of
      involvement in inhalant use. METHODS: Historical accounts of childhood exposure
      to physical or sexual abuse were compared among nonusers of inhalants (n = 197),
      light inhalant users (n = 64), and heavy inhalant users (n = 24). Crude and
      adjusted odds ratios were used to compare informants with no history of inhalant
      use with those having a history of light inhalant use and those having a history
      of heavy inhalant use. RESULTS: Heavy inhalant use was associated with history of
      any child abuse (adjusted odds ratio [OR] = 4.6) and physical abuse (adjusted OR
      = 3.8). Light inhalant use showed no association with child-abuse history.
      CONCLUSIONS: Child abuse may be an important correlate of extensive involvement
      in inhalant use. The findings invite speculation with respect to a hypothetical
      causal role for child abuse in the etiology of inhalant use. The lack of support
      for causality in this study underscores the need for replication and more
      carefully designed longitudinal research.

PMID- 9184504
TI  - The AIDS epidemic among Spanish drug users: a birth cohort-associated phenomenon.
AB  - OBJECTIVES: In Spain the number of new acquired immunodeficiency syndrome (AIDS)
      cases among injection drug users continues to rise. The time trend up to 1994 has
      been analyzed, with special attention paid to the different generations. METHODS:
      The source for injection drug use-related cases was the Spanish AIDS Register.
      Independent analyses of annual specific rates were run for each sex with the use
      of an age-period-cohort log-linear model. RESULTS: After adjustment for age and
      year of diagnosis, AIDS incidence related to injection drug use is associated
      with specific birth cohorts. Rising values are observed in the successive
      generations born during the 1950s, peaking in men born in 1962 and women born in
      1964. In subsequent cohorts, there is a marked falloff in incidence for both
      sexes, but this decline is seen to halt in men from the 1972 birth cohort
      onwards. The overall period effect is upward, yet the trend flattens in the last
      years. There is a pronounced age effect with maximum values in men and women at
      ages 29 and 27, respectively. CONCLUSIONS: It is essential to urge avoidance of
      risk behaviors in new generations.

PMID- 9184505
TI  - Recent trends in breast cancer mortality among white and black US women.
AB  - OBJECTIVES: Time trends in breast cancer mortality were analyzed from 1970 to
      1992 among White and Black US women aged 25 and over. METHODS: Mortality data
      from the National Center for Health Statistics were summarized within three
      periods 1970 to 1979, 1980 to 1988, and 1989 to 1992. The annual change was
      calculated as the average yearly percentage of change based on the logistic
      model. RESULTS: For White women of all ages, breast cancer mortality decreased by
      1.6% (95% confidence interval = -2.0%, -1.1%) per year on average during 1989 to
      1992, in contrast to the flat mortality rates observed during the 1970s and a
      0.5% average annual increase during 1980 to 1988. The decline was observed for
      White women under age 60, among whom breast cancer mortality had been decreasing,
      and for White women aged 60 to 79, among whom breast cancer mortality had been
      increasing, but it was not observed among Black women. CONCLUSIONS: The long
      awaited decline in US breast cancer mortality has finally appeared, although only
      among White women. The possible contributions are changes in inherent risk of
      disease, changes in treatment effectiveness, and increased use of screening
      mammography.

PMID- 9184506
TI  - Race and mammography use in two North Carolina counties.
AB  - OBJECTIVES: This study investigated racial differences in mammography use and
      their association with physicians' recommendations and other factors. METHODS:
      The study used 1988 survey data for 948 women 50 years of age and older from the
      New Hanover Breast Cancer Screening Program. Racial differences in terms of
      physician recommendation, personal characteristics, health characteristics, and
      attitudes toward breast cancer and mammography were examined. Factors at least
      minimally associated with race and use were included in multivariate logistic
      regression analyses to examine the effect of race while controlling for other
      factors. RESULTS: In comparison with White women. Black women were half as likely
      to report ever having had a mammogram (27% vs 52%) and having a mammogram in the
      past year (17% vs 36%). Black women also significantly less often reported
      physician recommendation (25% vs 52%). Although Black and White women differed
      significantly in other characteristics, multivariate logistic regression analyses
      indicated that physician recommendation accounted for 60% to 75% of the initial
      racial differences in mammography use. CONCLUSIONS: Understanding physicians'
      recommendations for breast cancer screening is a critical first step to
      increasing mammography use in disadvantaged populations.

PMID- 9184507
TI  - Ethnic differences in birthweight: the role of lifestyle and other factors.
AB  - OBJECTIVES: The purpose of this study was to expand the search for risk factors
      for low birthweight and to find new explanations for the ethnic-group disparities
      in birth outcomes. METHODS: The subjects were 1150 pregnant women from six ethnic
      groups (African American, Chinese, Dominican, Puerto Rican, Mexican, and White)
      who received prenatal care at clinics in New York and Chicago between December
      1987 and December 1989. Two interviews were conducted during the second and third
      trimesters of pregnancy. RESULTS: The study, after controlling for poverty and
      other birthweight correlates, showed that living in public housing and believing
      that chance plays a major role in determining one's health status were negatively
      associated with birthweight. Having a stable residence was positively related to
      birthweight. Material hardship, social adversity, perceived racial
      discrimination, physical abuse, anxiety, and depression were not associated with
      birthweight. CONCLUSIONS: The negative role of an impoverished living environment
      and feelings of helplessness, as well as the positive role of having a stable
      form of social support, suggest new directions for research on the causes of low
      birthweight and the ethnic disparities in US birth outcomes.

PMID- 9184508
TI  - Cross-cultural measurements of psychological well-being: the psychometric
      equivalence of Cantonese, Vietnamese, and Laotian translations of the Affect
      Balance Scale.
AB  - OBJECTIVES: This paper evaluates the cultural equivalence of Cantonese,
      Vietnamese, and Laotian translations of the Affect Balance Scale. METHODS: The
      scale was completed by 399 Vietnamese, 193 Laotian, 756 Cantonese, and 319
      English speakers who were participants in the Clarke Institute-University of
      Toronto Refugee Resettlement Project (n = 1667). RESULTS: Confirmatory factor
      analyses indicated a good fit between the hypothesized two-factor model (separate
      factors for positive and negative affect) across the original English-language
      version and each of the Asian-language translations. Factorial invariance
      (numbers and patterns of factor loadings) was evident across all versions of the
      scale. No evidence of item bias was detected by mixed Language x Item analyses of
      variance. Acceptable reliability was observed; coefficient alphas ranged from .62
      to .72 for positive affect and from .62 to .70 for negative affect items.
      CONCLUSIONS: These findings substantiate the cultural equivalence of the three
      translations of the scale for population health research. Important future
      research directions made possible by the availability of culturally equivalent
      instruments are discussed.

PMID- 9184510
TI  - Socioeconomic status and racial and ethnic differences in functional status
      associated with chronic diseases.
AB  - OBJECTIVES: This study examined the relationships between wealth and income and
      selected racial and ethnic differences in health. METHODS: Cross-sectional data
      on a national sample of 9744 men and women aged 51 through 61 from the 1992
      Health and Retirement Survey were analyzed to examine the association between
      socioeconomic status and racial and ethnic differences in functional status among
      those with hypertension, diabetes, a heart condition, and arthritis. RESULTS:
      Compared with Whites, African Americans report higher rates of hypertension,
      diabetes, and arthritis, while Hispanics report higher rates of hypertension and
      diabetes and a lower rate of heart conditions. Accounting for differences in
      education, income, and wealth had little effect on these prevalence differences.
      In general, among those with chronic diseases, African Americans and Hispanics
      reported worse function than Whites. This disadvantage was eliminated in every
      case by controlling for socioeconomic status. CONCLUSIONS: While socioeconomic
      status, including wealth, accounts for much of the difference in functional
      status associated with these chronic diseases. It plays a relatively small role
      in explaining differences in the prevalence of chronic disease, possibly
      reflecting different causal pathways.

PMID- 9184509
TI  - Region of birth and mortality from circulatory diseases among black Americans.
AB  - OBJECTIVES: This study examines the relationship between birth-place and
      mortality from circulatory diseases among American Blacks. METHODS: All Black
      deaths from circulatory diseases (International Classification of Diseases, 9th
      Revision. codes 390 through 459) were extracted from the National Center for
      Health Statistics mortality detail files for 1979 through 1991. Age-specific and
      age-adjusted mortality rates with 95% confidence intervals were calculated for
      males and females for combinations of five regions of residence at birth and four
      regions of residence at death. RESULTS: Males had higher mortality rates from
      circulatory diseases than females in every regional combination of birthplace and
      residence at death. For both genders, the highest rates were for those who were
      born in the South but died in the Midwest; the lowest rates were for those who
      were born in the West but died in the South. Excess mortality for both Southern
      born males and females begins at ages 25 through 44. CONCLUSIONS: There is a
      region-of-birth component that affects mortality risk from circulatory diseases
      regardless of gender or residence at time of death. We must examine how early
      life experiences affect the development of circulatory disorders.

PMID- 9184511
TI  - Potentially avoidable hospitalizations: inequalities in rates between US
      socioeconomic groups.
AB  - OBJECTIVES: The National Hospital Discharge Survey (NHDS) was used to evaluate
      potentially avoidable hospital conditions as an indicator of equity and
      efficiency in the US health care system. METHODS: With the use of 1990 data from
      the NHDS, the National Health Interview Survey, and the census, national rates of
      hospitalization were calculated for avoidable conditions by age, race, median
      income of zip code, and insurance status. RESULTS: An estimated 3.1 million
      hospitalizations were for potentially avoidable conditions. This was 12% of all
      hospitalizations in 1990 (excluding psychiatric admissions, women with
      deliveries, and newborns). Rates of potentially avoidable hospitalizations were
      higher for persons living in middle- and low-income areas than for persons living
      in high-income areas, and were higher among Blacks than among Whites. These class
      and racial differences were also found among the privately insured. Differences
      among income and racial groups for persons aged 65 and over were not significant.
      CONCLUSIONS: Inequalities in potentially avoidable hospitalizations suggest
      inequity and inefficiency in the health care delivery system. Avoidable hospital
      conditions are a useful national indicator to monitor access to care.

PMID- 9184512
TI  - The relationship between the race/ethnicity of generalist physicians and their
      care for underserved populations.
AB  - OBJECTIVES: The purpose of this study was to examine empirically the relationship
      between physicians' race or ethnicity and their care for medically underserved
      populations. METHODS: Generalist physicians who received the MD degree in 1983 or
      1984 (n = 1581) were surveyed. The personal and background characteristics of
      four racial/ethnic groups of physicians were compared with the characteristics of
      their patients. RESULTS: When the potentially confounding variables of gender,
      childhood family income, childhood residence, and National Health Services Corps
      financial aid obligations were controlled, generalist physicians from
      underrepresented minorities were more likely than their nonminority counterparts
      to care for medically underserved populations. CONCLUSIONS: Physicians from
      underrepresented minorities are more likely than others to care for medically
      underserved populations.

PMID- 9184513
TI  - An experimental analysis of sociocultural variables in sales of cigarettes to
      minors.
AB  - OBJECTIVES: This study assessed the role of age, racial/ethnic group, and gender,
      as well as that of other sociocultural variables, in minors' access to tobacco.
      METHODS: Thirty-six minors attempted to purchase cigarettes once in each of 72
      stores (2592 purchase attempts). The minors represented equal numbers of girls
      and boys; 10-year-olds, 14-year-olds, and 16-year-olds; and Whites, Blacks, and
      Latinos. Equal numbers of stores were in Black, White, and Latino neighborhoods.
      RESULTS: Older children were more likely than younger ones to be sold cigarettes,
      and Latino children were more likely than Whites to be sold cigarettes. Older
      Black children (irrespective of gender) were the single most likely group to be
      sold cigarettes. Cigarettes were significantly more likely to be sold to children
      by male than female clerks and in specific sociocultural contexts. CONCLUSIONS:
      Interventions with retailers must address sociocultural variables to improve
      effectiveness in reducing minors' access to tobacco.

PMID- 9184514
TI  - Psychiatric disorders among American Indian and white youth in Appalachia: the
      Great Smoky Mountains Study.
AB  - OBJECTIVES: This study examined prevalence of psychiatric disorders, social and
      family risk factors for disorders, and met and unmet needs for mental health care
      among Appalachian youth. METHODS: All 9-, 11-, and 13-year-old American Indian
      children in an 11-county area of the southern Appalachians were recruited,
      together with a representative sample of the surrounding population of White
      children. RESULTS: Three-month prevalences of psychiatric disorders were similar
      (American Indian, 16.7%; White, 19.2%). Substance use was more common in American
      Indian children (9.0% vs 3.8% in White children), as was comorbidity of substance
      use and psychiatric disorder (2.5% vs 0.9%). American Indian poverty, family
      adversity (e.g., parental unemployment, welfare dependency), and family deviance
      (parental violence, substance abuse, and crime) rates were higher, but the rate
      of family mental illness, excluding substance abuse, was lower. Child psychiatric
      disorder and mental health service use were associated with family mental illness
      in both ethnic groups but were associated with poverty and family deviance only
      in White children. Despite lower financial barriers, American Indian children
      used fewer mental health services. CONCLUSIONS: This study suggests that poverty
      and crime play different roles in different communities in the etiology of child
      psychiatric disorder.

PMID- 9184515
TI  - Ethnic differences in the prevalence of nonmalignant respiratory disease among
      uranium miners.
AB  - OBJECTIVES: This study (1) investigates the relationship of nonmalignant
      respiratory disease to underground uranium mining and to cigarette smoking in
      Native American, Hispanic, and non-Hispanic White miners in the Southwest and (2)
      evaluates the criteria for compensation of ethnic minorities. METHODS: Risk for
      mining-related lung disease was analyzed by stratified analysis, multiple linear
      regression, and logistic regression with data on 1359 miners. RESULTS: Uranium
      mining is more strongly associated with obstructive lung disease and radiographic
      pnuemoconiosis in Native Americans than in Hispanics and non-Hispanic Whites.
      Obstructive lung disease in Hispanic and non-Hispanic White miners is mostly
      related to cigarette smoking. Current compensation criteria excluded 24% of
      Native Americans who, by ethnic-specific standards, had restrictive lung disease
      and 4.8% who had obstructive lung disease. Native Americans have the highest
      prevalence of radiographic pneumoconiosis, but are less likely to meet spirometry
      criteria for compensation. CONCLUSIONS: Native American miners have more
      nonmalignant respiratory disease from underground uranium mining, and less
      disease from smoking, than the other groups, but are less likely to receive
      compensation for mining-related disease.

PMID- 9184516
TI  - Motor vehicle rollover and static stability: an exposure study.
AB  - OBJECTIVES: This study examined vehicle rollovers in terms of site-specific
      exposure and speeds of vehicles of varying stability. METHODS: Fifty-one rollover
      sites in two states were visited at the same time of day and day of week as the
      rollover. A sample of vehicles moving in the same direction as the rollover were
      observed, and vehicle-specific data were obtained from identification numbers.
      RESULTS: Low stability, exacerbated by the addition of passengers, increased the
      risk of rollover. Speed was not correlated with stability and is not a
      confounder. CONCLUSIONS: Rollovers could be substantially reduced if motor
      vehicles were manufactured with a static stability of 1.2 or greater.

PMID- 9184517
TI  - Relative risk in the news media: a quantification of misrepresentation.
AB  - OBJECTIVES: This study quantifies the representativeness with which the print
      news media depict mortality. METHODS: The proportion of mortality-related copy in
      samples of national print media was compared with the proportion of actual deaths
      attributable to the leading causes of US mortality over a 1-year period. RESULTS:
      For every tested cause of death, a significant disproportion was found between
      amount of text devoted to the cause and the actual number of attributable deaths.
      Underrepresented causes included tobacco use (23% of expected copy) and heart
      disease (33%); overrepresented causes included illicit use of drugs (1740%),
      motor vehicles (1280%), and toxic agents (1070%). CONCLUSIONS: The news media
      significantly misrepresent the prevalence of leading causes of death and their
      risk factors. This misrepresentation may contribute to the public's distorted
      perceptions of health threats.

PMID- 9184518
TI  - The impact of public assistance factors on the immunization levels of children
      younger than 2 years.
AB  - OBJECTIVES: This study examined how children's immunization status varied with
      enrollment in the Women, Infants, and Children (WIC); Aid to Families with
      Dependent Children (AFDC); food stamp; and Medicaid programs. METHODS: A
      statewide survey was used to determine the percentage of children less than 2
      years of age who were up to date for diphtheria, tetanus, and pertussis; polio;
      and measles, mumps, and rubella vaccines. RESULTS: WIC and uninsured children
      were more likely and AFDC and Medicaid children less likely to be up to date than
      others. CONCLUSIONS: The higher immunization status of WIC and uninsured children
      suggests that integrating immunization practices with government programs may be
      effective.

PMID- 9184519
TI  - A pricing strategy to promote low-fat snack choices through vending machines.
AB  - OBJECTIVES: This study examined the role of price on purchases of low-fat snacks
      from vending machines. METHODS: Sales of low-fat and regular snacks were
      monitored in nine vending machines during a 4-week baseline, a 3-week
      intervention in which prices of low-fat snacks were reduced 50%, and 3 weeks
      postintervention. RESULTS: The proportion of low-fat snacks purchased was 25.7%,
      45.8%, and 22.8% in the three periods, respectively. Total snack purchases did
      not vary by period. CONCLUSIONS: Reducing relative prices may be effective in
      promoting lower-fat food choices in the population. Vending machines may be a
      feasible method for implementing such nutrition interventions.

PMID- 9184520
TI  - A persistent rise in mortality among injection drug users in Rome, 1980 through
      1992.
AB  - OBJECTIVES: The purpose of the study was to analyze overall and cause-specific
      mortality among injection drug users in Rome. METHODS: A cohort of 4200 injection
      drug users was enrolled in drug treatment centers from 1980 through 1988 and
      followed up until December 1992. RESULTS: The age-adjusted mortality rate from
      all causes increased from 7.8/1000 person-years in 1985/86 to 27.7/1000 in
      1991/92. The rise was mainly attributable to acquired immunodeficiency syndrome
      (AIDS), but mortality from overdose and other causes increased as well. The
      cumulative risk of death by the age of 40 was 29.3%. CONCLUSIONS: The impact of
      AIDS deaths appears to be additional to a persistent increase of mortality for
      all other causes.

PMID- 9184521
TI  - Injection drug use among homeless adults with severe mental illness.
AB  - OBJECTIVES: This study examined injection drug use among homeless men and women
      with severe mental illness in two sites. METHODS: The data were drawn from
      related clinical trials conducted in Baltimore (101 men, 49 women) and Boston (85
      men, 33 women). RESULTS: The percentages of homeless men with a history of
      injection drug use were 26% in Baltimore and 16% in Boston; the corresponding
      rates among homeless women were 8% and 6%. CONCLUSIONS: Taken together, these and
      previous results suggest high lifetime prevalences of injection drug use-and
      associated risks of HIV transmission-in this elusive population.

PMID- 9184523
TI  - No butts about it: public smoking ends in Vermont.

PMID- 9184522
TI  - Antibody testing and condom use among heterosexual African Americans at risk for
      HIV infection: the National AIDS Behavioral Surveys.
AB  - OBJECTIVES: This study describes predictions of condom use and human
      immunodeficiency virus (HIV) antibody testing in a population-based sample of
      African-American heterosexuals who reported HIV risk behavior. METHODS: Data were
      taken from the National AIDS Behavioral Surveys. RESULTS: Of the African-American
      respondents, 22% reported some risk for HIV infection; of those, 24% had been
      tested for HIV. CONCLUSIONS: Prevention messages encouraging HIV testing and
      condom use have not resulted in high rates of self-protective behavior among
      African Americans. Future prevention interventions must focus on specific
      motivations and barriers with regard to engaging in preventive behavior among
      specific age, gender, and educational-level groups within the population of
      African Americans at risk for HIV infection.

PMID- 9184524
TI  - Operation Tot Shots: an awareness campaign for parents during kindergarten
      registration.

PMID- 9184525
TI  - Tuberculosis screening at a syringe exchange program.

PMID- 9184526
TI  - Interpreting HIV prevalence and incidence among Americans: bridging data and
      public policy.

PMID- 9184528
TI  - Liver transplants and the decline in deaths from liver disease.

PMID- 9184527
TI  - Quantifying the expected vs potential impact of a risk-factor intervention
      program.

PMID- 9184529
TI  - Alternative models for controlling smoking among adolescents.

PMID- 9184530
TI  - The driver's role in automobile safety.

PMID- 9184531
TI  - The end of the chronic disease era.

PMID- 9184532
TI  - US HIV prevalence estimates: why the delay in publication?

PMID- 9184534
TI  - HLA-DPB1 and TAP1 polymorphisms in sarcoidosis.

PMID- 9184533
TI  - Finding disease genes. From cystic fibrosis to sarcoidosis. Thomas A. Neff
      Lecture.

PMID- 9184535
TI  - Elevated levels of extracellular superoxide dismutase in chronic lung disease and
      characterization of genetic variants.

PMID- 9184536
TI  - Genetics of atopy and asthma. The rationale behind promoter-based candidate gene
      studies.

PMID- 9184537
TI  - Susceptibility loci regulating total serum IgE levels, bronchial
      hyperresponsiveness, and clinical asthma map to chromosome 5q.

PMID- 9184538
TI  - Association of the Gln 27 beta 2-adrenoceptor polymorphism and IgE variability in
      asthmatic families.

PMID- 9184539
TI  - The molecular genetics of hereditary hemorrhagic telangiectasia.

PMID- 9184540
TI  - The presence of genetic anticipation suggests that the molecular basis of
      familial primary pulmonary hypertension may be trinucleotide repeat expansion.

PMID- 9184541
TI  - Patterns of gene expression in human airway epithelial cells.

PMID- 9184542
TI  - Transcriptional control in the developing lung. The Parker B. Francis
      lectureship.

PMID- 9184543
TI  - Human thyroid transcription factor-1. Functional characterization of the protein
      and analysis of protein/DNA interactions on the minimal promoter region.

PMID- 9184544
TI  - Identification of a cDNA for Ca++-independent phospholipase A2 of lung lamellar
      bodies/lysosomes.

PMID- 9184546
TI  - Transfer and expression of neutrophil inhibitory factor gene in endothelial and
      epithelial cells prevent neutrophil adhesion.

PMID- 9184545
TI  - Transient gene transfer and expression in the lung.

PMID- 9184547
TI  - Glycosylated polylysines. Nonviral vectors for gene transfer into cystic fibrosis
      airway epithelial cells.

PMID- 9184548
TI  - Genetic determinants of pulmonary hypertension in fawn-hooded rats.

PMID- 9184550
TI  - Pulmonary cytokine gene therapy. Adenoviral-mediated murine interferon gene
      transfer compartmentally activates alveolar macrophages and enhances bacterial
      clearance.

PMID- 9184549
TI  - Transcriptional regulation of the surfactant protein-A gene in fetal lung.

PMID- 9184551
TI  - Suppressive effect of antisense DNA of platelet-derived growth factor on murine
      pulmonary fibrosis with silica particles.

PMID- 9184552
TI  - Genes that control lung liquid. Giles F. Filley Lecture.

PMID- 9184553
TI  - Differential effects of adenoviral-mediated transfer of Na+/K(+)-ATPase subunit
      genes in lung epithelial cells.

PMID- 9184554
TI  - Genomic organization and developmental expression of aquaporin-5 in lung.

PMID- 9184555
TI  - Role of the epithelial sodium channel in lung liquid clearance.

PMID- 9184556
TI  - The structure and function of surfactant protein-A.

PMID- 9184557
TI  - Coordination of genetic, epigenetic, and environmental factors in lung
      development, injury, and repair.

PMID- 9184558
TI  - Polycationic lipid-mediated gene transfer to the abnormal pulmonary circulation.

PMID- 9184559
TI  - Clinical features and natural history of severe alpha 1-antitrypsin deficiency.
      Roger S. Mitchell Lecture.

PMID- 9184560
TI  - In vivo adenovirus-mediated expression of human pre-elafin, a potent neutrophil
      elastase inhibitor.

PMID- 9184561
TI  - Rat prostacyclin synthase. Cloning and regulation of gene expression in the lung.

PMID- 9184562
TI  - Surfactant protein-B deficiency.

PMID- 9184563
TI  - TTF-1 is an epithelial morphoregulatory transcriptional factor.

PMID- 9184564
TI  - Adenovirus-mediated gene transfer of the proteoglycan biglycan induces
      fibroblastic responses in the lung.

PMID- 9184565
TI  - Surfactant protein and CC-10 expression in acute lung injury and in response to
      keratinocyte growth factor.

PMID- 9184566
TI  - Adenoviral vectors for hepatic gene transfer in animals.

PMID- 9184567
TI  - The effects of sialoglycoconjugates on adenovirus-mediated gene transfer to
      epithelial cells in vitro and in human airway xenografts.

PMID- 9184568
TI  - Gene therapy for lung cancer and mesothelioma.

PMID- 9184569
TI  - Carboxypeptidase M. Variable expression in normal human lung and inactivation in
      lung cancer.

PMID- 9184570
TI  - Conference summary. Gene-based therapies for inherited and acquired disorders of
      the lung.

PMID- 9184571
TI  - Paul Dudley White International Lecture. Our future society. A global challenge.

PMID- 9184572
TI  - NHLBI stops arrhythmia study: implantable cardiac defibrillators reduce deaths.

PMID- 9184573
TI  - Credentialing for coronary interventions. Practice makes perfect.

PMID- 9184574
TI  - Is hepatocyte growth factor a protein with cardioprotective activity in the
      ischemic heart?

PMID- 9184575
TI  - Cardiac risk stratification for high-risk vascular surgery.
AB  - BACKGROUND: The best strategy for cardiac risk assessment before high-risk
      vascular surgery remains controversial. A cardiac risk stratification protocol
      was evaluated in patients undergoing high-risk vascular surgery. Our
      investigation paralleled the elaboration of the American College of Cardiology/
      American Heart Association (ACC/AHA) Guidelines for Perioperative Cardiovascular
      Evaluation for Noncardiac Surgery and is highly comparable to the proposed
      guidelines. METHODS AND RESULTS: A cardiac risk stratification protocol was
      evaluated prospectively in 203 patients scheduled for aortic surgery. Key points
      of the study were cardiac mortality/morbidity and cost-effectiveness. Patients
      were stratified into low (n = 101), intermediate (n = 79), and high (n = 23)
      cardiac risk after clinical predictors. After stratification, the degree of
      estimated functional capacity assessed by treadmill exercise and daily living
      activities and expressed by metabolic equivalents (METs) was critical for further
      cardiac evaluation. In intermediate-risk patients with an estimated functional
      capacity < 5 METs and in all high-risk patients, noninvasive cardiac testing
      and/or subsequent medical care were performed. Noninvasive testing was considered
      necessary in 41 patients, coronary angiography in 7, and myocardial
      revascularization in 1. Overall hospital mortality was 3.5%. Cardiac mortality
      and morbidity were 1% and 12.4%, respectively. CONCLUSIONS: Cardiac risk
      stratification for high-risk vascular surgery patients, according to a protocol
      similar to the ACC/AHA Guidelines for Cardiovascular Evaluation for Noncardiac
      Surgery, demonstrated excellent clinical outcome. This approach appears to be a
      safe and economical strategy for preoperative cardiac evaluation.

PMID- 9184576
TI  - Intravenous immune globulin in the therapy of myocarditis and acute
      cardiomyopathy.
AB  - BACKGROUND: Although an autoimmune pathogenesis has been postulated for dilated
      cardiomyopathy, immunosuppressive therapy has not been shown to be effective in
      clinical trials. Immune modulatory therapy with immune globulin is an effective
      therapy for Kawasaki disease in children, and recent data suggest that it
      improves ventricular function in children with new-onset dilated
      cardiomyopathies. The role of immune globulin therapy in adults with this
      disorder has not previously been evaluated. METHODS AND RESULTS: Ten patients
      were treated with high-dose intravenous immune globulin infusions (2 g/kg). All
      were hospitalized with NYHA class III to IV heart failure, left ventricular
      ejection fraction (LVEF) < 0.40, and symptoms for < 6 months at the time of
      presentation. One patient died before the completion of therapy. The remaining 9
      were discharged, and LVEF was reassessed 12 months after therapy. LVEF improved
      from 0.24 +/- 0.02 (mean +/- SEM) at baseline to 0.41 +/- 0.04 at follow-up (P =
      .003). All 9 patients improved functionally to NYHA class I to II, and there have
      been no subsequent hospitalizations for heart failure during the course of follow
      up. CONCLUSIONS: In this series of patients with new-onset dilated cardiomyopathy
      treated with high-dose immune globulin, LVEF improved 17 EF units. The
      effectiveness of intravenous immune globulin therapy in this disorder should be
      evaluated in a randomized, multicenter trial.

PMID- 9184577
TI  - Relation of operator volume and experience to procedural outcome of percutaneous
      coronary revascularization at hospitals with high interventional volumes.
AB  - BACKGROUND: Although an inverse relation between physician caseload and
      complications has been conclusively demonstrated for several surgical procedures,
      such data are lacking for percutaneous coronary intervention, and the ACC/AHA
      guidelines requiring > or = 75 cases per year for operator "competency" are
      considered by some physicians to be arbitrary. METHODS AND RESULTS: From quality
      controlled databases at five high-volume centers, models predictive of death and
      the composite outcome of death, Q-wave infarction, or emergency bypass surgery
      were developed from 12,985 consecutively treated patients during 1993 through
      1994. Models had moderate to high discriminative capacity (area under ROC curves,
      0.65 to 0.85), were well calibrated, and were not overfitted by standard tests.
      These models were used for risk adjustment, and the relations between both yearly
      caseload and years of interventional experience and the two adverse outcome
      measures were explored for all 38 physicians with > or = 30 cases per year. The
      average physician performed a mean +/- SD of 163 +/- 24 cases per year and had
      been practicing angioplasty for 8 +/- 5 years. Risk-adjusted measures of both
      death and the composite adverse outcome were inversely related to the number of
      cases each operator performed annually but bore no relation to total years of
      experience. Both adverse outcomes were more closely related to the logarithm of
      caseload (for death, r = .37, P = .01; for death, Q-wave infarction, or bypass
      surgery, r = .58, P < .001) than to linear caseload. CONCLUSIONS: In this
      analysis, high-volume operators had a lower incidence of major complications than
      did lower-volume operators, but the difference was not consistent for all
      operators. If these data are validated, their implications for hospital,
      physician, and payer policy will require exploration.

PMID- 9184578
TI  - Relationship between physician and hospital coronary angioplasty volume and
      outcome in elderly patients.
AB  - BACKGROUND: With the expectation that physicians who perform larger numbers of
      coronary angioplasty procedures will have better outcomes, the American College
      of Cardiology/ American Heart Association guidelines recommend minimum physician
      volumes of 75 procedures per year. However, there is little empirical data to
      support this recommendation. METHODS AND RESULTS: We examined in-hospital bypass
      surgery and death after angioplasty according to 1992 physician and hospital
      Medicare procedure volume. In 1992, 6115 physicians performed angioplasty on
      97,478 Medicare patients at 984 hospitals. The median numbers of procedures
      performed per physician and per hospital were 13 (interquartile range, 5 to 25)
      and 98 (interquartile range, 40 to 181), respectively. With the assumption that
      Medicare patients composed one half to one third of all patients undergoing
      angioplasty, these median values are consistent with an overall physician volume
      of 26 to 39 cases per year and an overall hospital volume of 196 to 294 cases per
      year. After adjusting for age, sex, race, acute myocardial infarction, and
      comorbidity, low-volume physicians were associated with higher rates of bypass
      surgery (P < .001) and low-volume hospitals were associated with higher rates of
      bypass surgery and death (P < .001). Improving outcomes were seen up to threshold
      values of 75 Medicare cases per physician and 200 Medicare cases per hospital.
      CONCLUSIONS: More than 50% of physicians and 25% of hospitals performing coronary
      angioplasty in 1992 were unlikely to have met the minimum volume guidelines first
      published in 1988, and these patients had worse outcomes. While more recent data
      are required to determine whether the same relationships persist after the
      introduction of newer technologies, this study suggests that adherence to minimum
      volume standards by physicians and hospitals will lead to better outcomes for
      elderly patients undergoing coronary angioplasty.

PMID- 9184579
TI  - 8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative
      marker of oxidant stress in vivo.
AB  - BACKGROUND: Myocardial reperfusion is believed to be associated with free radical
      injury. However, indexes of oxidative stress in vivo have been limited by their
      poor specificity and sensitivity. Isoprostanes are stable products of arachidonic
      acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a
      sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG)
      F2 alpha. METHODS AND RESULTS: To address its utility as an index of oxidative
      stress during coronary reperfusion, we measured urinary levels by gas
      chromatography/mass spectrometry in a canine model of coronary thrombolysis, in
      patients with acute myocardial infarction treated with thrombolytic therapy, and
      in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2
      alpha was unchanged after circumflex artery occlusion in a canine model of
      coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol
      creatinine) but increased significantly (P < .05) immediately after reperfusion
      (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients
      (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8
      pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8
      pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3
      pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3
      pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15
      minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/-
      50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass
      surgery (n = 5). Corresponding changes in spin adduct formation, found with
      electron paramagnetic resonance, were noted in 2 patients. CONCLUSIONS: These
      data support the hypothesis that free radical generation occurs during myocardial
      reperfusion. Measurement of isoprostane production may serve as a noninvasive
      index of oxidative stress.

PMID- 9184580
TI  - Preconditioning of human myocardium with adenosine during coronary angioplasty.
AB  - BACKGROUND: It is unknown whether adenosine can precondition human myocardium
      against ischemia in vivo. METHODS AND RESULTS: Thirty patients were randomized to
      receive a 10-minute intracoronary infusion of adenosine (2 mg/min) or normal
      saline; 10 minutes later, they underwent percutaneous transluminal coronary
      angioplasty (PTCA; three 2-minute balloon inflations 5 minutes apart). In control
      patients, the ST-segment shift on the intracoronary ECG was significantly greater
      during the first inflation than during the second and third inflations,
      consistent with ischemic preconditioning. In contrast, in adenosine-treated
      patients, there were no differences in ST-segment shift during the three
      inflations. The ST-segment shift was significantly smaller in the adenosine
      treated group compared with the control group during all three inflations. The
      reduction in ST-segment shift afforded by adenosine during the first inflation (
      72% versus first inflation in control subjects) was greater than that afforded by
      ischemic preconditioning in control subjects (-52% during the third versus first
      inflation). Measurements of chest pain score paralleled those of ST-segment
      shift. Adenosine had no effect on baseline regional wall motion as determined by
      quantitative two-dimensional echocardiography. Thus, intracoronary infusion of
      adenosine before PTCA rendered the myocardium remarkably resistant to subsequent
      ischemia. Judging from the intracoronary ECG, the protection provided by
      adenosine was even superior to that provided in control subjects by the ischemia
      associated with the first two balloon inflations. Infusion of adenosine had no
      major adverse effects in patients undergoing PTCA of the left anterior descending
      or circumflex arteries. CONCLUSIONS: Adenosine preconditions human myocardium
      against ischemia in vivo. Pretreatment with adenosine is remarkably effective
      (even more effective than ischemic preconditioning) and could be used
      prophylactically to attenuate ischemia in selected patients undergoing PTCA of
      the left anterior descending coronary artery. Whether adenosine can be safely
      infused into the right or the circumflex coronary artery in the presence of a
      temporary pacemaker remains to be established.

PMID- 9184581
TI  - Incidence and predictors of bleeding after contemporary thrombolytic therapy for
      myocardial infarction. The Global Utilization of Streptokinase and Tissue
      Plasminogen activator for Occluded coronary arteries (GUSTO) I Investigators.
AB  - BACKGROUND: Although the benefit of thrombolytic therapy in reducing mortality in
      acute myocardial infarction is well established, the types of bleeding and risk
      factors for bleeding are less well described in large trials. METHODS AND
      RESULTS: We analyzed the baseline characteristics, outcomes, and incidence of
      bleeding by location, severity, and treatment assignment among 41,021 patients in
      the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903
      patients for whom there were complete data, 1.2% suffered severe bleeding and
      11.4% experienced moderate hemorrhage at a variety of sites. The most common
      sources of bleeding were procedure related. The thrombolytic regimen was strongly
      related to the incidence of bleeding; comparatively more bleeding was seen with
      the therapies of streptokinase plus intravenous heparin and the streptokinase and
      tissue plasminogen activator plus intravenous heparin combination. In
      multivariate analysis, the four most powerful independent predictors of
      hemorrhage were older age, lighter body weight, female sex, and African ancestry;
      they remained the most important predictors of bleeding when multivariate
      analysis was performed on patients who did not undergo invasive procedures. The
      presence of serious hemorrhage was associated with other undesirable outcomes
      (recurrent events, left ventricular dysfunction, arrhythmia, or stroke).
      CONCLUSIONS: Important predictors of bleeding in this population are increased
      age, lighter weight, female sex, African ancestry, and experiencing invasive
      procedures. Other nonhemorrhagic adverse clinical outcomes were associated with
      moderate and severe bleeding, which was in turn associated with increased length
      of hospital stay and mortality at 30 days.

PMID- 9184582
TI  - Three-dimensional mapping of the initiation of nonsustained ventricular
      tachycardia in the human heart.
AB  - BACKGROUND: Elucidation of the electrophysiological mechanisms of nonsustained
      ventricular tachycardia (VT) in humans is required to define the relationship
      between nonsustained VT and sustained VT. This goal requires, at least in part,
      analysis of transmural ventricular activation in patients with both sustained and
      nonsustained VTs. METHODS AND RESULTS: We analyzed three-dimensional
      intraoperative cardiac maps of extrastimuli and beats during 44 nonsustained VTs
      and the initiating beats of 6 sustained VTs from six patients with healed
      myocardial infarcts who were undergoing arrhythmia surgery. The coupling
      interval, total activation time, and diastolic interval of each extrastimulus and
      beat of nonsustained VT were compared with counterparts during sustained VT.
      Sites activated last during extrastimuli initiating nonsustained or sustained VTs
      occurred in the same region, and activation times were comparable. However, the
      site of earliest activation during the initial or subsequent beats of
      nonsustained VT was discordant from the site activated earliest during the first
      and subsequent beats of sustained VT in 74% of cases. The mean variance in
      coupling interval, but not total activation time or diastolic interval, was
      significantly greater for VT that terminated before the 10th cycle than for VT
      that sustained. When analyzed from the last extrastimulus up to the fifth VT
      cycle, the standard deviation of the coupling interval, but not of the total
      activation time, was greater for nonsustained than for sustained VTs. Electrode
      density was sufficient to define an arrhythmia mechanism for 36 beats of
      nonsustained VT. Twenty-one (58%) initiated in the subendocardium, midmyocardium,
      or epicardium by a macroreentrant mechanism, and 15 (42%) initiated in the
      subendocardium by a focal mechanism. CONCLUSIONS: Compared with sustained VT,
      nonsustained VT initiates at discordant sites, is characterized by oscillations
      in coupling interval but not in total activation time, and initiates by either a
      macroreentrant or a focal mechanism.

PMID- 9184583
TI  - Termination of ventricular tachycardia in the human heart. Insights from three
      dimensional mapping of nonsustained and sustained ventricular tachycardias.
AB  - BACKGROUND: To define the electrophysiological basis for the termination of
      ventricular tachycardia (VT), three-dimensional cardiac mapping and analysis of
      the terminal beats of nonsustained VT and beats of sustained VT were performed in
      six patients with healed myocardial infarcts. METHODS AND RESULTS: Termination of
      VT was due to activation from multiple initiation sites that were discordant from
      those responsible for the maintenance of sustained VT in 45% of cases, to
      repetitive activation from single sites that were discordant from those
      responsible for the maintenance of sustained VT in 24% of cases, or to activation
      from sites concordant with the sites of repetitive activation during sustained VT
      in 31% of cases. Sustained VT was characterized by occasional shifting of
      initiation sites, even after the tachycardia entered the stable monomorphic
      phase. Mapping was of sufficient density to define the mechanisms for 21
      terminating beats of VT. In 5 cases, termination was due to intramural reentry,
      which initiated with the total activation time of the preceding beat of 204 +/-
      11 milliseconds (ms) but terminated primarily because of a decrease in total
      activation time (144 +/- 23 ms, P = .03) that was associated with the development
      of intramural conduction block or with significant changes in the activation
      sequence along the reentrant circuit. In 16 cases, terminal beats were initiated
      by a focal mechanism on the basis of the absence of intervening electrical
      activity from the termination of the preceding beat to the initiation of the
      terminating beat (172 +/- 9 ms). Focal activation was associated with less
      conduction delay of the preceding beat (115 +/- 6 ms) than terminating reentrant
      beats (P < .001) and usually terminated suddenly without oscillations in cycle
      length or total activation time. CONCLUSIONS: Termination of VT is associated
      with alterations in initiation sites that are most often discordant from those
      maintaining sustained VT and is due to either reentrant or focal mechanisms.

PMID- 9184584
TI  - Complex electrophysiological characteristics in atrioventricular nodal reentrant
      tachycardia with continuous atrioventricular node function curves.
AB  - BACKGROUND: Although typical atrioventricular nodal reentrant tachycardia (AVNRT)
      with discontinuous AV node function curves has been well studied, there has been
      a lack of any significant information about AVNRT without evidence of dual AV
      nodal pathway physiology during atrial extrastimulus testing or atrial pacing.
      METHODS AND RESULTS: Group 1 included 9 patients with continuous curves during
      atrial extrastimulus testing but without a jump (> or = 50 ms) of the atrial-His
      bundle (AH) interval during incremental atrial pacing. The maximal AH interval
      during atrial pacing (266 +/- 61 versus 168 +/- 27 ms, P = .007) or extrastimulus
      testing (290 +/- 60 versus 176 +/- 18 ms, P = .005) shortened significantly after
      ablation. Antegrade and retrograde AV node properties were similar before and
      after ablation. Group 2 included 14 patients with continuous curves and a jump of
      the AH interval during incremental atrial pacing. The atrial pacing cycle length
      with 1:1 AV conduction and effective refractory period (ERP) of the antegrade AV
      node increased significantly, whereas the maximal AH interval during atrial
      pacing (358 +/- 70 versus 203 +/- 28 ms, P = .001) or extrastimulus testing (338
      +/- 75 versus 196 +/- 34 ms, P = .002) shortened significantly after ablation.
      Group 3 included 24 patients with discontinuous curves. The maximal AH interval
      during atrial pacing or extrastimulus testing and the ERP of the antegrade fast
      AV node shortened, whereas the ERP of the antegrade AV node increased
      significantly after ablation. The maximal AH interval before ablation, extent of
      decrease in maximal AH interval after ablation, ERP of the retrograde AV node
      before ablation, and tachycardia cycle length were significantly shorter in group
      1 than groups 2 and 3. CONCLUSIONS: In AVNRT with continuous AV node function
      curves, dual AV nodal pathway physiology may or may not be demonstrated during
      atrial pacing. Significant shortening of the maximal AH interval during atrial
      pacing after radiofrequency ablation suggests successful elimination of AVNRT.

PMID- 9184585
TI  - Assessment of a newly recognized association. Carotid sinus hypersensitivity and
      denervation of sternocleidomastoid muscles.
AB  - BACKGROUND: Carotid sinus syndrome has been reported recently to be associated
      with chronic denervation of the sternocleidomastoid muscles. To further
      understand the relationship between carotid mechanoreceptors and
      sternocleidomastoid denervation, the present study investigated the relation
      between the results of carotid sinus massage and electromyographic activity of
      the sternocleidomastoid muscles in patients without syncope. METHODS AND RESULTS:
      Patients were selected prospectively if they fulfilled strict exclusion criteria,
      particularly the absence of a history of syncope, pacemaker implantation, or
      drugs known to modify the behavior of the autonomic nervous system. A right and
      left carotid massage was performed for 10 seconds in 30 patients (22 men; mean
      age, 67.3 +/- 6.5 years). The results (monitoring for heart rate and blood
      pressure) were classified as normal, doubtful, or hypersensitive carotid sinus.
      Sternocleidomastoid electromyography activity was recorded from the right and
      left sides, and the results were classified as normal, moderate denervation, and
      severe denervation. Carotid sinus massage was normal in 13 patients (43%),
      doubtful in 9 (30%), and abnormal in 8 (27%). Electromyographic activity of the
      sternocleidomastoids was normal in 13 patients (43%) and revealed moderate
      denervation in 7 (24%) and severe chronic denervation in 10 (33%). The results of
      carotid sinus massage and sternocleidomastoid electromyography were highly
      concordant in each patient (kappa = .592, P < .00001) and in each side (right,
      kappa = .381, P < .03; left, kappa = .390, P < .01). CONCLUSIONS: Carotid sinus
      hypersensitivity and chronic denervation is a common finding in individuals older
      than 50 years of age. These two entities are significantly related, suggesting a
      pathophysiological relation of one to the other.

PMID- 9184586
TI  - Enhanced expression of hepatocyte growth factor/c-Met by myocardial ischemia and
      reperfusion in a rat model.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a multifunctional factor implicated
      in tissue regeneration, wound healing, and angiogenesis. Circulating HGF is
      reportedly elevated during the early stage of myocardial infarction. However, its
      precise effect on the heart is unknown. To evaluate the regulation of HGF in
      ischemically damaged myocardium, the production of HGF and its high-affinity
      receptor, c-Met, was studied in a rat model of myocardial ischemia and
      reperfusion. METHODS AND RESULTS: The plasma concentration of HGF began to
      increase within 1 hour of reperfusion after 1 hour of ischemia. The peak level
      was reached at 3 hours after reperfusion. Northern blotting revealed that HGF
      mRNA expression in the heart was augmented threefold at 24 and 48 hours and
      remained elevated by twofold at 120 hours after the myocardium was reperfused.
      The signal for c-met, high-affinity HGF receptor mRNA, was also upregulated
      parallel to upregulation for HGF. In the kidney, liver, lung, and spleen, HGF
      mRNA was also maximally increased at 12 hours after reperfusion. However, c-met
      was not upregulated in these organs. Immunohistochemical studies disclosed that
      capillary endothelial and interstitial cells, including infiltrating macrophages,
      were intensely stained for HGF, whereas capillary endothelial cells in the
      reperfused myocardium were positive for c-Met. CONCLUSIONS: This study is the
      first to show that myocardial ischemia and reperfusion induced HGF expression in
      various organs in vivo. These results indicate that HGF/c-Met plays a role in
      capillary endothelial cell regeneration in the ischemically injured heart.

PMID- 9184587
TI  - Changes in ischemic tolerance and effects of ischemic preconditioning in middle
      aged rat hearts.
AB  - BACKGROUND: Although both clinical and animal studies have shown that ischemic
      tolerance is reduced in the senescent myocardium, it has not been clarified when
      myocardium becomes more vulnerable to ischemia. Preconditioning protects the
      hearts of young adult animals of various species, but its effects are not
      identical in human studies. We investigated whether ischemic tolerance and the
      effect of preconditioning decreased in isolated hearts of middle-aged rats.
      METHODS AND RESULTS: The hearts of young adult rats (12 weeks old: group Y, n =
      44) and middle-aged rats (50 weeks old: group M, n = 44) were subjected to global
      ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also
      subjected to preconditioning and then to 20 (group Y, n = 22) or 15 (group M, n =
      22) minutes of ischemia followed by reperfusion. Left ventricular developed
      pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased
      by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (%
      LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1;
      creatine phosphate, 17.0 to 23.1 mumol/g dry wt) and reduced left ventricular end
      diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to
      132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release
      after ischemia in group Y. Preconditioning exerted opposite effects in group M (%
      LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 mumol/g dry wt;
      and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with
      increases in the incidence of reperfusion-induced ventricular fibrillation (0% to
      62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M.
      CONCLUSIONS: These results indicate that hearts became more vulnerable to
      ischemia with age and that the beneficial effects of preconditioning were
      reversed in middle-aged rat hearts.

PMID- 9184588
TI  - Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle
      cells.
AB  - BACKGROUND: Agonist-induced Ca2+ entry is thought to be mediated by capacitative
      Ca2+ entry other than L-type Ca2+ channels in vascular smooth muscle cells
      (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated.
      Our objective was to examine the effect of external Mg2+ on capacitative Ca2+
      entry in cultured rat aortic VSMCs. METHODS AND RESULTS: Three doses of external
      Mg2+ concentration (nominally 0, 1, and 5 mmol/L) were used. After exposure to 1
      mumol/L, angiotensin II (Ang II) in Ca(2+)-free medium, addition of Ca2+ to the
      medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i),
      indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells
      preincubated with high external Mg2+ concentrations or with 1 mumol/L nifedipine.
      After VSMCs in Ca(2+)-free medium were exposed to 1 mumol/L thapsigargin, which
      inhibits the sarcoplasmic reticulum Ca(2+)-ATPase and depletes Ca2+ stores,
      addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating
      capacitative Ca2+ entry. This entry pathway was found to be independent of
      dihydropyridine-sensitive Ca2+ channels and inhibited by increased external Mg2+
      concentration. External Mg2+ concentration did not influence Ca2+ efflux across
      the plasma membrane after stimulation with Ang II plus thapsigargin. CONCLUSIONS:
      Results suggest that in VSMCs, capacitative Ca2+ entry is reduced by external
      Mg2+. This mechanism may explain in part the inhibitory effect of external Mg2+
      on Ca2+ handling.

PMID- 9184589
TI  - Efferent vagal innervation of the canine atria and sinus and atrioventricular
      nodes. The third fat pad.
AB  - BACKGROUND: The purpose of this study was to investigate the functional pathways
      of efferent vagal innervation to the atrial myocardium and sinus and
      atrioventricular (AV) nodes. METHODS AND RESULTS: Using vagally induced atrial
      effective refractory period shortening, slowing of spontaneous sinus rate, and
      prolongation of AV nodal conduction time as end points of vagal effects, we
      determined the actions of phenol and epicardial radiofrequency catheter ablation
      (RFCA) applied to different sites at or near the atrial myocardium to inhibit
      these responses. We found that efferent vagal fibers to the atria are located
      both subepicardially and intramurally or subendocardially. Most efferent vagal
      fibers to the atria appear to travel through a newly described fat pad located
      between the medial superior vena cava and aortic root (SVC-Ao fat pad), superior
      to the right pulmonary artery, and then project onto two previously noted fat
      pads at the inferior vena cava-left atrial junction (IVC-LA fat pad) and the
      right pulmonary vein-atrial junction (RPV fat pad) and to both atria. A few vagal
      fibers may bypass the SVC-Ao fat pad and go directly to the IVC-LA or RPV fat pad
      and then innervate the atrial myocardium. Vagal fibers to the sinus and AV nodes
      also converge at the SVC-Ao fat pad (a few fibers to the sinus node go directly
      to the RPV fat pad) before projecting to the RPV and IVC-LA fat pads. Long-term
      vagal denervation of the atria and sinus and AV nodes can be produced by RFCA of
      these fat pads and results in vagal denervation supersensitivity. Vagal
      denervation prevents induction of atrial fibrillation in this model. CONCLUSIONS:
      The newly described SVC-Ao fat pad receives most of the vagal fibers to the atria
      and sinus and AV nodes. Elimination of the fat pads with RFCA selectively vagally
      denervated the atria and sinus and AV nodes.

PMID- 9184590
TI  - Images in cardiovascular medicine. Cardiovascular disease in ankylosing (Marie
      Strumpell) spondylitis.

PMID- 9184591
TI  - Images in cardiovascular medicine. Extraction of an Accufix atrial J-shaped
      support wire.

PMID- 9184592
TI  - Trans fatty acids, plasma lipid levels, and risk of developing cardiovascular
      disease. A statement for healthcare professionals from the American Heart
      Association.

PMID- 9184593
TI  - Phytochemicals and cardiovascular disease. A statement for healthcare
      professionals from the American Heart Association.

PMID- 9184594
TI  - Involvement of proprioceptive feedback in brainstem-triggered convulsions.
AB  - PURPOSE: In rodents, specific motor components of generalized convulsive seizures
      depend on two distinct anatomic substrates: (a) forebrain networks are
      responsible for facial and forelimb clonus with or without rearing and falling;
      and (b) brainstem networks are responsible for running-bouncing fits and tonic
      convulsions. To investigate the requirement of proprioceptive inputs in the
      generation of these two different types of seizures, we compared the effects of
      neuromuscular blockade by D-tubocurarine on the EEG expression of brainstem- and
      forebrain-triggered seizures. METHODS: Unilateral electrical stimulations were
      applied for 50 consecutive days in freely moving male adult rats through a
      bipolar electrode aimed at the dorsal hippocampus (n = 5), the occipital cortex
      (n = 4), the inferior colliculus (n = 6), or the midbrain reticular formation (n
      = 6). Two days after the last stimulation, rats were paralyzed with d
      tubocurarine and stimulated in the same way. RESULTS: In brainstem structures,
      the first electrical stimulation induced tonic seizures concomitant with low
      voltage cortical activity; repetition of daily stimulations progressively induced
      tonic-clonic seizures associated with high-amplitude cortical spike-wave
      discharges. After immobilization by d-tubocurarine, brainstem stimulations failed
      to induce any EEG paroxysm. In forebrain structures, repeated electrical
      stimulations produced a classic kindling with progressive occurrence of clonic
      seizures associated with large cortical discharges; d-tubocurarine left unchanged
      the EEG pattern of these latter seizures. CONCLUSIONS: These data suggest that
      proprioceptive reafferentation resulting from movement is necessary for the
      generation of self-sustained brainstem seizures but is not implicated in the
      elaboration of forebrain seizures.

PMID- 9184595
TI  - Local perfusion of diazepam attenuates interictal and ictal events in the
      bicuculline model of epilepsy in rats.
AB  - PURPOSE: We evaluated the efficacy of local perfusion of diazepam (DZP) in
      suppression of EEG spikes and behavioral seizures produced by bicuculline
      methiodide (BMI) applied to rat sensory motor cortex and hippocampus. METHODS:
      Data were obtained from 37 rats implanted with EEG head plugs and perfusion
      cannulas. BMI 4 mM, 5 microliters was infused on neocortex through the epidural
      space in 23 rats. BMI 0.1 mM, 2 microliters was infused into the left hippocampus
      in 14 rats. RESULTS: DZP 0.75-1.0 mg markedly reduced the spiking to a level of
      9.9 +/- 15.8% of baseline for DZP as compared with 90.2 +/- 57.9% of baseline for
      vehicle-treated rats. DZP reduced spiking in a hippocampal BMI focus to 1.9 +/-
      2.4% of baseline spiking, as compared with 98.0 +/- 95.6% of that in vehicle
      treated animals. The amount of spread of solution was estimated with methylene
      blue (MB) injections. Ictal events also were attenuated. In most of the animals,
      systemic levels of DZP were unmeasurable and injection on the contralateral side
      did not reduce spiking. CONCLUSIONS: These findings suggest that focal
      application of antiepileptic drugs (AEDs) in brain may be a useful new avenue for
      therapy of intractable partial seizures.

PMID- 9184596
TI  - Lamotrigine reduces voltage-gated sodium currents in rat central neurons in
      culture.
AB  - PURPOSE: To study the mechanism or mechanisms of action of lamotrigine (LTG) and,
      in particular, to establish its effects on the function of NA+ channels in
      mammalian central neurons. METHODS: Rat cerebellar granule cells in culture were
      subjected to the whole-cell mode of voltage clamping under experimental
      conditions designed to study voltage-gated Na+ currents. RESULTS: Extracellular
      application of LTG (10-500 microM, n = 21) decreased in a dose-related manner a
      tetrodotoxin-sensitive inward current that was elicited by depolarizing commands
      (from -80 to +20 mV). The peak amplitude of this Na(+)-mediated current was
      diminished by 38.8 +/- 12.2% (mean +/- SD, n = 6) during application of 100
      microM LTG, and the dose-response curve of this effect indicated an IC50 of 145
      microM. The reduction in the inward currents produced by LTG was not associate
      with any significant change in the current decay, whereas the voltage dependency
      of the steady-state inactivation shifted toward more negative values (midpoint of
      the inactivation curve: -47.5 and -59.0 mV under control conditions and during
      application of 100 microM LTG, respectively, n = 4). CONCLUSIONS: Our findings
      indicate that LTG reduces the amplitude of voltage-gated Na+ inward current in
      rat cerebellar granule cells and induces a negative shift of the steady-state
      inactivation curve. Both mechanisms may be instrumental in controlling the
      repetitive firing of action potentials (AP) that occurs in neuronal networks
      during seizure activity.

PMID- 9184597
TI  - Community-based study of Lennox-Gastaut syndrome.
AB  - PURPOSE: Before 1986, the spectrum of childhood epilepsies, including Lennox
      Gastaut syndrome (LGS) and Doose syndrome (DS), known collectively as "epilepsia
      myoclonica astatica," was believed to represent a single disease. More recently,
      some investigators have considered these syndromes to be parts of a continuum. To
      clarify these theories, neurobiologic factors of the syndromes were studied to
      determine which qualities were shared and which were unique. METHODS: A
      retrospective (1975-1985), community-based (Helsinki metropolitan area and the
      province of Uusimaa) study was designed to seek children with features of LGS and
      DS. It was assumed that recall bias and the selection of documented history would
      be similar throughout the group. Ranks of increasing pathology were assigned to
      different seizure types, EEG results, and drug treatments. A similar procedure
      was applied to epidemiologic data. Spearman rank-order correlations were
      calculated to determine which features correlated with LGS and which correlated
      with less severe epilepsy. RESULTS: The survey comprised 75 patients with broadly
      defined LGS. The annual incidence was 2 in 100,000 children aged 0 to 14 years.
      Prenatal or perinatal abnormalities did not correlate with severity of epilepsy.
      As compared with the relatively favorable ranks, the severe epilepsy ranks were
      more often associated with an early onset of epilepsy, an infectious disease at
      the onset, delayed development before epilepsy, abnormalities in neurologic or
      neuroradiologic examinations, and a deteriorating course of the condition.
      CONCLUSIONS: Patients with LGS are more likely than patients with less severe
      epilepsy to have a younger age at onset of epilepsy, an infection or both, and a
      deteriorating course of the condition.

PMID- 9184599
TI  - Incidence of epilepsy in rural central Ethiopia.
AB  - PURPOSE: To study the incidence of epilepsy in a rural area of Ethiopia. METHODS:
      A community-based study was performed in a random sample of villages with 61,686
      inhabitants in a rural area of central Ethiopia. In a door-to-door survey, all
      inhabitants in the study area were interviewed about seizures. A standardized
      protocol was used. All new cases with epilepsy that had occurred since a previous
      study was made 3.5 years earlier were included. Fifty-three of the subjects were
      investigated with EEG. RESULTS: One-hundred thirty-nine incident cases were
      identified, corresponding to an annual incidence of 64 in 100,000 inhabitants
      [95% confidence interval (CI) 44-84]. The corresponding rate for males was 72 (CI
      42-102); for females, it was 57 (CI 31-84). The highest age-specific incidence
      occurred in the youngest age groups (0-9 years); the next highest was in the
      group aged 10-19 years. Generalized convulsive seizures occurred in 69%, partial
      seizures occurred in 20%, and unclassifiable seizures occurred in 11%. Seizures
      occurred daily in 10% and weekly in another 14%; 33% had monthly seizures. Twenty
      two percent had a family history of epilepsy. A history of head trauma was
      ascertained in 5.7% and was the most common possible etiologic factor identified.
      Thirteen percent were treated with antiepileptic drugs (AEDs). CONCLUSIONS: The
      incidence of epilepsy in Ethiopia is high. A high incidence in combination with a
      prevalence of epilepsy in the study area comparable to that in the rest of the
      world may be explained by a high degree of spontaneous remission of epilepsy
      and/or a high mortality due to epilepsy. Despite health education on epilepsy
      given to the community, a minority of subjects were treated with AEDs, which may
      reflect the inadequacies of the health services and transportation difficulties
      faced by the patients.

PMID- 9184598
TI  - Reproductive activity and offspring health of young adults with childhood-onset
      epilepsy: a controlled study.
AB  - PURPOSE: To study reproductive activity and offspring health in a prospective
      follow-up setting. METHODS: After a 35-year follow-up of a population-based
      patient cohort with childhood-onset "epilepsy only," 100 (56.8%) of 176 surviving
      patients were shown to have "epilepsy only", i.e., recurrent unprovoked seizures
      with no associated neuroimpairment. Their reproductivity and offspring health
      were compared with those of matched controls. RESULTS: The marriage rate and
      fertility of patients with "epilepsy only" were significantly reduced as compared
      with those of matched controls. Continuation of antiepileptic drug (AED)
      treatment was significantly associated with reduced reproduction, whereas
      occurrence of seizures during the previous 5 years was not. The incidence of
      epilepsy was nine times greater among the children of patients than among those
      of controls. No higher risks were observed in pregnancy or delivery in patients,
      nor were increased rates of birth defects in their offspring than in those of
      controls. Exposure to AEDs during pregnancy did not increase these risks.
      CONCLUSIONS: Patients with "epilepsy only" since childhood have fewer marriages
      and fewer children than expected. However, when they marry, their pregnancies and
      deliveries are unremarkable and their children do not have increased congenital
      health problems. Obviously, etiologies causative of both epilepsy and associated
      neurological impairments are more harmful to the course of pregnancy and delivery
      and offspring health than are those resulting in "epilepsy only".

PMID- 9184600
TI  - Incidence of first epileptic seizures in the canton of Geneva, Switzerland.
AB  - PURPOSE: We wished to determine the incidence of first provoked and nonprovoked
      epileptic seizures in the canton of Geneva, Switzerland. METHODS: Between June 1,
      1990 and May 31, 1991, we collected all cases of suspected epileptic seizures
      referred to the two hospitals of the county of Geneva, Switzerland and to the
      private neurologists of the town. The diagnosis probability was based on clinical
      data from the patient chart and the EEG data. The classification of risk factors
      proposed by the International League Against Epilepsy (ILAE) Commission on
      Epidemiology and Prognosis was used. RESULTS: In all, 273 cases were collected.
      The age-adjusted incidence rate (U.S. population as standard) is 69.4 in 100,000.
      We observed a bimodal distribution of the cases with age (71 in the group aged 0
      10 years and 107.5 in those aged > 60 years). Ninety-seven cases were classified
      as having provoked seizures (incidence: 25.2 in 100,000). Alcohol consumption
      (29.8%) and cerebrovascular diseases were the most frequent causes (16.4%). One
      hundred seventy-six cases were classified as having unprovoked seizures
      (incidence: 45.6 in 100,000) with the following distribution: seizures in
      relation with a stable cerebral condition, 69 cases (incidence: 17.9); seizures
      in relation with an evolutive cerebral condition, 27 cases (incidence: 7); and
      seizures of unknown etiology, 80 cases (incidence: 20.8). CONCLUSIONS: The
      incidence rate of first epileptic seizures in the canton of Geneva is quite
      similar to that reported in a French study (Epilepsia (1990;31:391-394) in which
      the same methodology for case ascertainment was used. Our data clearly
      demonstrate that the classification of risk factors proposed by the ILAE
      Commission on Epidemiology and Prognosis is useful and particularly easy to use
      in epidemiological surveys.

PMID- 9184601
TI  - Recognition and classification of seizures in infants.
AB  - PURPOSE: We wished to assess the reliability of the International League Against
      Epilepsy (ILAE) seizure classification system applied to infantile seizures and
      to test a proposed new classification. METHODS: We first analyzed 39 seizures in
      20 infants (aged 1-26 months) recorded with simultaneous closed-circuit
      television and EEG (CCTV/EEG). EEGs and videotapes of all seizures were
      independently analyzed by two epileptologists blinded to clinical histories.
      Videotapes of each seizure were reviewed without simultaneous EEG (phase 1), and
      printouts of ictal EEGs were assessed without behavioral correlates (phase II).
      The observers classified seizures according to ILAE criteria. Interrater
      agreement was assessed by the kappa statistic. RESULTS: Agreement on EEG features
      (phase II) was moderate (= 0.54) in identifying focal ictal onsets and
      substantial (= 0.79) in identifying generalized onsets. In contrast, analysis of
      videotapes showed substantial disagreement between observers in terms of
      classifying seizures as partial or generalized. Therefore, agreement between
      observers for partial was slight (= 0.14) and fair for generalized seizures (=
      0.26). Similarly, conclusions of the observers as compared with those of a
      consensus panel were divergent for both partial (= 0.18) and generalized seizures
      (= 0.30). We therefore developed an alternative classification scheme and
      retested interrater agreement in a review of 50 seizures in 25 other infants.
      With this classification scheme, there was substantial agreement between
      observers (= 0.72). CONCLUSIONS: With clinical observations and interictal EEGs,
      seizures in infants cannot be reliably classified by current ILAE criteria. In
      contrast, a proposed new classification scheme based solely on semiology showed
      substantial reliability.

PMID- 9184602
TI  - Early discontinuation of treatment in children with uncomplicated epilepsy: a
      prospective study with a model for prediction of outcome.
AB  - PURPOSE: The main purpose of the present study was to identify predictor
      variables with significant influence on seizure outcome after discontinuation of
      treatment in children with uncomplicated epilepsy and to analyze whether these
      variables, included in a prognostic model could identify children in whom 1-year
      treatment would be sufficient. METHODS: Before initiation of treatment in
      children aged 2-16 years with uncomplicated epilepsy, the duration of treatment
      was randomized to 1 year (group I) or 3 years (group II). At the end of the
      allotted period, treatment was discontinued in 161 children who had been seizure
      fre during the previous 6 months. The mean follow-up period after treatment was
      5.8 years. Twenty-three predictor variables were analyzed by survival methods
      regarding their influences on the outcome. RESULTS: At the latest follow-up
      check, 60 children (37%) had relapsed. The following predictor variables were
      selected by multiple regression analysis and constituted a model with a simple
      scoring system: age at seizure onset; seizure type; generalized, irregular spike
      wave activity on EEG after 1 year of treatment; and persistent 3-Hz spike-wave
      activity after 6 months of treatment in children with absence epilepsy. In group
      I, the remission rate was 73% in children with high prognostic scores, 10% in
      children with low scores, and 40% in those with intermediate scores (log-rank
      test, p = 0.0001). CONCLUSIONS: After 1 year of treatment, our prognostic model
      identified children in whom treatment could be withdrawn at that time. Our model
      should be easily applicable in clinical practices and may be of clinical
      importance in determining the duration of treatment in children with
      uncomplicated epilepsy.

PMID- 9184603
TI  - Reappraisal of polytherapy in epilepsy: a critical review of drug load and
      adverse effects.
AB  - PURPOSE: We reviewed the literature to determine whether an analysis of published
      data could clarify the relationship between antiepileptic drug (AED) polytherapy
      and adverse affects (AE). We highlight the problems encountered. METHODS: We made
      a Medline-search for articles published between 1974 and 1994 reporting the
      number of AE and doses or serum levels of every AED, per patient or treatment
      group, and used the PDD/DDD ratio to calculate AED load per patient from doses or
      the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/DDD
      is the sum of ratios of the actual prescribed daily doses divided by the
      published average therapeutic dose of each drug. The OSL/AToxL is the sum of each
      observed serum level divided by its average toxic level. RESULTS: We retrieved
      118 trial reports. Most had to be excluded because of incomplete reporting of
      concomitant medication or AE. The data of the 15 articles selected for further
      analysis indicate a relationship between drug load and number of AE. We noted no
      relationship between the number of AEDs administered and AE. In add-on studies,
      the difference in neurotoxicity between the active and placebo arm may be
      obscured if the relative increase in drug load is small, as exemplified by the
      study of McGuire et al.. CONCLUSIONS: Articles reporting add-on trials of new
      AEDs generally do not provide detailed information about the basic medication to
      which the new AED is added, which makes calculation of total drug load
      impossible. Furthermore, often only frequency of AE is reported, not severity or
      development of tolerance, making it difficult to judge the impact of AE. However,
      despite the paucity of available information, we present some evidence that
      toxicity in AED polytherapy may be related to total drug load, rather than to the
      number of drugs administered. Therefore, the present trend to reject polytherapy
      for fear of increased toxicity is not warranted, which removes one of the
      objections to initiating specific research to prove or disprove the value of AED
      combinations as long as the drug load is appropriate.

PMID- 9184604
TI  - Cortical and hippocampal volume deficits in temporal lobe epilepsy.
AB  - PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine
      the extent of volume abnormalities in the hippocampus and in extrahippocampal
      brain regions in localization-related epilepsy of temporal lobe origin (TLE).
      METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined
      with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were
      candidates for temporal lobe resection. Measures were adjusted for normal
      variation due to intracranial volume and age based on 72 healthy male controls.
      Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)]
      patients and a subset of 49 age range-matched controls were examined with
      analysis of variance (ANOVA). RESULTS: As compared with controls, patients with
      TLE had smaller temporal lobe and frontoparietal region gray matter volumes,
      bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger
      ventricular volumes. In contrast to these bilateral tissue volume deficits,
      hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal
      lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and
      occurred in both temporal and extra-temporal cortical regions in TLE, whereas
      hippocampal deficits were related to the side of the epileptogenic focus. These
      data suggest that brain abnormalities in TLE are not limited to the epileptogenic
      region.

PMID- 9184605
TI  - Volumetric magnetic resonance imaging evidence of bilateral hippocampal atrophy
      in mesial temporal lobe epilepsy.
AB  - PURPOSE: We measured absolute volumes and volume differences of hippocampi in
      patients with mesial temporal lobe epilepsy (MTLE) using volumetric magnetic
      resonance imaging (MRI) to determine the extent of bilateral atrophy in MTLE and
      to relate hippocampal volumes (HV) to outcome of temporal lobectomy. METHODS: HV
      and hippocampal differences (HD) were measured in 40 patients with MTLE
      determined by pathology of hippocampal sclerosis (HS) and compared with those of
      age-matched controls. Results were matched with surgical outcome. RESULTS:
      Hippocampi contralateral to lobectomy (right hippocampi 2.96 +/- 0.49 cm3, left
      3.14 +/- 0.51 cm3) were significantly smaller than those of controls (right
      hippocampi 3.73 +/- 0.52 cm3, left 3.60 +/- 0.51 cm3) but were significantly
      larger than hippocampi ipsilateral to lobectomy (right hippocampi 2.63 +/- 0.61
      cm3, 2.18 cm3) as compared across groups by analysis of variance (ANOVA: F =
      27.2, p < 0.0001). The smaller hippocampus was ipsilateral to lobectomy in 39 of
      40 cases. Seven of 40 MTLE patients (18%) had bilateral atrophy, defined by
      volumes of each hippocampi 2 SD lower than control means. Surgical outcome was
      independent of hippocampal asymmetry and bilateral atrophy measured by chi-square
      and Fisher's exact tests. CONCLUSIONS: We determined that most patients with MTLE
      have some degree of bilateral, asymmetric hippocampal pathology. However,
      asymmetry and bilateral atrophy have no clear relation to surgical outcome.

PMID- 9184606
TI  - The diagnostic yield of a second EEG after partial sleep deprivation: a
      prospective study in children with newly diagnosed seizures.
AB  - PURPOSE: To assess the diagnostic yield of a repeated EEG (REPEEG) after partial
      sleep deprivation (SD) in children and adolescents with one or more seizures who
      previously had had a standard EEG (STDEEG) without epileptiform abnormalities
      (EAs). In the literature, 32-75% of such REPEEGs after SD were reported to show
      EA. METHODS: In a prospective, multicentred study, we selected children aged 1
      month to 16 years with one or more idiopathic or remote symptomatic newly
      diagnosed seizures. A REPEEG was recorded in children without EAs in their
      STDEEG. RESULTS: Of 552 children and adolescents who entered the study, 243 (44%)
      had a STDEEG without EAs. In 177 (73% of eligible children), REPEEGs were
      recorded after SD. We found EAs in 61 (34.5%) REPEEGs and new nonepileptiform
      abnormalities in five (1%). In 552 children in the total cohort, the REPEEG thus
      added 11% with EAs to the 56% with EAs in the STDEEG. Of REPEEGs, 81% included
      sleep compared with 20% of STDEEGs. In about half the REPEEGs, EAs occurred
      during sleep only. One child had tonic-clonic seizures probably related to the
      SD. CONCLUSIONS: One third of REPEEGs yielded new diagnostic information.
      Partial, age-dependent SD was highly effective in inducing sleep, which is
      important because in many cases EAs were found only during EEG recording in
      sleep. The procedure was safe and convenient.

PMID- 9184607
TI  - Neuronal generators of visual evoked potentials in humans: visual processing in
      the human cortex.
AB  - PURPOSE: We wished to define the localization of cortical generators of visual
      (pattern) evoked potentials (VEP) and the temporal sequence of activation in the
      occipital region. METHODS: In 4 candidates for epilepsy surgery, a large array of
      subdural electrodes was placed over occipital areas. Checkerboard pattern
      reversal stimuli were generated and the epileptogenic focus was localized and
      functionally mapped. Magnetic resonance imaging did not show any occipital
      lesions in any of the 4 patients. RESULTS: The area first activated was the
      lingual gyrus in the mesial occipital lobe (negative potential peaks at
      approximately 70 ms), followed by an area superior to the calcarine fissure
      (negative peaks at approximately 80 ms). Later (starting at approximately 90 ms),
      there were positive potentials over the occipital pole and lingual gyrus,
      followed by potentials at the lateral occipital lobe. CONCLUSIONS: These data
      support the idea that VEP are generated in the mesial and lateral occipital
      cortex by different circumscribed neuronal generators with different latencies of
      activation. The scalp-recorded N1 and P1 potential peaks most likely derive from
      the progressive activation of neuronal masses in different regions of the
      occipital lobe.

PMID- 9184609
TI  - ILAE Commission Report. The epidemiology of the epilepsies: future directions.
      International League Against Epilepsy.

PMID- 9184608
TI  - IgA and IgG2 deficiency associated with zonisamide therapy: a case report.
AB  - PURPOSE: To report a previously undescribed adverse effect, IgA/IgG subclass
      deficiency associated with zonisamide (ZNS) therapy. METHODS: Serum IgA and IgG
      subclass levels were determined by the turbidimetric immunoassay and enzyme
      linked immunosorbent assay, respectively, in a 2-year-old boy with postmeningitis
      sequelae who was treated by ZNS. RESULTS: Four months after initiation of ZNS,
      combined deficiency of IgA and IgG2 was noted. After cessation of ZNS, serum IgA
      level was promptly increased. IgG2 level was gradually increased, but remained
      subnormal after 7 months. CONCLUSIONS: This case documents, for the first time,
      the action of ZNS on IgG immune system as well as IgA system. If patients with
      ZNS therapy showed IgA deficiency and recurrent infections, it is preferable to
      check serum IgG subclass concentrations as well.

PMID- 9184610
TI  - Apoptosis: neuronal death by design.

PMID- 9184612
TI  - Chronic neuroleptic exposure in bipolar outpatients.
AB  - BACKGROUND: Although the chronic use of neuroleptic medications is generally
      discouraged in patients with bipolar disorder, data on the actual extent of this
      practice are relatively scarce. METHOD: All bipolar patients receiving treatment
      at the Connecticut Mental Health Center on September 1, 1994, were identified
      through a computerized administrative database; the medical record was then
      examined. Patients were included in the study if (1) the last two recorded
      diagnoses in the chart were concordant for bipolar disorder and (2) the patient
      had not been hospitalized in the past year. RESULTS: Of 49 patients meeting
      review criteria, 33 (67%) met criteria for chronic neuroleptic exposure. The mean
      +/- SD continuous neuroleptic dosage for these 33 outpatients was 416 +/- 527
      mg/day chlorpromazine (CPZ) equivalents. The dosage distribution was skewed, with
      17 (52%) receiving < or = 200 mg/day CPZ [corrected] equivalents. CONCLUSION:
      Chronic neuroleptic administration occurred frequently in our sample of
      nonhospitalized bipolar outpatients.

PMID- 9184611
TI  - A comparison of nefazodone and fluoxetine on mood and on objective, subjective,
      and clinician-rated measures of sleep in depressed patients: a double-blind, 8
      week clinical trial.
AB  - BACKGROUND: Previous small trials have suggested that nefazodone does not
      suppress rapid-eye-movement (REM) sleep or increase REM latency in depressed
      patients, in contrast to fluoxetine. The effects of nefazodone and fluoxetine on
      sleep architecture and on clinician- and patient-rated sleep measures were
      directly compared in this 8-week, multicenter, double-blind, randomized, parallel
      group study. METHOD: Forty-four outpatients with moderate to severe, nonpsychotic
      major depressive disorder (DSM-III-R) and insomnia were randomly assigned to
      receive nefazodone (Days 1-7, 200 mg/day; Days 8-56, 400 mg/day) or fluoxetine
      (Days 1-56, 20 mg/day). Sleep measures were obtained at baseline, while patients
      were unmedicated, and at Weeks 2, 4, and 8 of treatment. RESULTS: In 43 evaluable
      patients (23 nefazodone, 20 fluoxetine), nefazodone and fluoxetine demonstrated
      similar antidepressant efficacy. All significant values were p < .05. Fluoxetine
      significantly decreased sleep efficiency and REM sleep and increased number of
      awakenings, Stage 1 sleep, and REM latency compared with baseline. In contrast,
      nefazodone significantly decreased percentage of awake and movement time and did
      not alter sleep efficiency or number of awakenings, Stage 1 or REM sleep, or REM
      latency compared with baseline. Nefazodone was associated with significantly less
      change from baseline for sleep efficiency, number of awakenings, percentage of
      awake and movement time, percentage of REM and Stage 1 sleep, and REM latency
      compared with fluoxetine. Both fluoxetine- and nefazodone-treated patients also
      showed significant improvement in some clinician- and patient-rated sleep
      disturbance scores, but nefazodone-treated patients improved to a significantly
      greater extent than fluoxetine-treated patients in most measures. CONCLUSION:
      While nefazodone and fluoxetine showed equivalent antidepressant efficacy, more
      objective, subjective, and clinician-rated measures of sleep disturbance were
      improved during treatment with nefazodone than with fluoxetine. These results
      suggest that antidepressant effects of medications can occur independently of
      drug-induced changes in objective, subjective, and clinician-rated measures of
      sleep. Further studies, including parallel placebo-controlled comparisons with
      nefazodone, are needed to further test this hypothesis.

PMID- 9184613
TI  - The role of the alliance in the pharmacologic treatment of depression.
AB  - BACKGROUND: The purpose of this study was to determine the influence of the
      therapeutic alliance on the efficacy of pharmacotherapy for depression. METHOD:
      The sample consisted of 31 depressed outpatients treated with antidepressants.
      The alliance was measured by the patient and therapist versions of the California
      Pharmacotherapy Alliance Scale. Treatment outcome was measured by the Hamilton
      Rating Scale for Depression and the Beck Depression Inventory, and the Symptom,
      Sign, Side-Effect Checklist was also completed. RESULTS: The alliance measures
      accounted for between 21% and 56% of the variance in the three outcome measures.
      By averaging across outcome measures, therapist perceptions of the alliance
      predicted 41% of the variance in improvement in depressive symptoms, where
      patient perceptions predicted 25%. Scores on both alliance measures were lower
      than those reported in studies of psychotherapy. Patient attitude toward
      medication was correlated with somatic complaints, but not with depression
      scores. Therapist perception of patient hostility correlated with patient
      depression. Patients differed in the way their alliance and outcome interacted,
      so that the association might be positive or negative. CONCLUSION: Alliance is
      correlated with outcome in pharmacotherapy management of depression, although
      there may be interindividual variability across patients. In the pharmacotherapy
      of depression, therapist perception of alliance is a better predictor of symptom
      outcome than patient perception, while the reverse is usually found in
      psychotherapy.

PMID- 9184614
TI  - Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the
      acute treatment of schizophrenia.
AB  - BACKGROUND: A relative lack of extrapyramidal symptoms (EPS, i.e., the syndromes
      of dystonia, parkinsonism, akathisia, dyskinesia) is one criterion used to
      determine whether an antipsychotic is "atypical." The extrapyramidal symptom
      profiles of the novel antipsychotic olanzapine and the conventional antipsychotic
      haloperidol were compared in a population of 2606 patients from three well
      controlled prospective clinical trials. METHOD: Extrapyramidal symptom data were
      analyzed for 1796 patients treated with olanzapine (5 to 20 mg/day) and 810
      patients treated with haloperidol (5 to 20 mg/day) for up to 6 weeks of therapy.
      Patients were monitored weekly by three methods of extrapyramidal symptom
      assessment: (1) detection of extrapyramidal adverse events (signs and symptoms)
      by casual observation, nonprobing inquiry, and spontaneous report; (2) objective
      rating scale scores: and (3) use of concomitant anticholinergic medications.
      Emergence of EPS was assessed by (1) analysis of the incidence of extrapyramidal
      syndrome categories based on adverse events, (2) the incidence of extrapyramidal
      syndromes based on categorical analysis of rating scale scores, (3) analysis of
      mean maximum change in rating scale scores, and (4) categorical analysis of
      anticholinergic medication use. Outcome of EPS was assessed by (1) analysis of
      mean change in rating scale scores at endpoint and (2) mean anticholinergic use
      at endpoint. RESULTS: Olanzapine was statistically significantly (p = .014, p <
      .001) superior to haloperidol in all four analyses related to emergence of EPS
      and in the two analyses related to outcome. Furthermore, during acute treatment,
      statistically significantly fewer patients treated with olanzapine (0.3%)
      discontinued the study because of any extrapyramidal adverse event than patients
      treated with haloperidol (2.7%, p < .001). CONCLUSION: Olanzapine exhibited a
      statistically significantly lower extrapyramidal symptom profile than the
      conventional antipsychotic haloperidol at comparably effective antipsychotic
      doses. The lower extrapyramidal symptom profile with olanzapine was evident
      despite statistically significantly more frequent use of anticholinergic drugs
      among haloperidol-treated patients. Fewer olanzapine-treated than haloperidol
      treated patients discontinued because of EPS, suggesting that olanzapine should
      contribute to better compliance with longer term maintenance treatment, with
      minimal anticholinergic-associated events.

PMID- 9184616
TI  - Reversible dyskinesia during bupropion therapy.

PMID- 9184615
TI  - Frontotemporal dementia: treatment response to serotonin selective reuptake
      inhibitors.
AB  - BACKGROUND: Patients with frontotemporal dementia (FTD) present initially with
      primarily behavioral rather than cognitive symptoms. Decreased serotonin receptor
      binding has been reported in the frontal lobes, temporal lobes, and hypothalamus
      in autopsy-proven FTD cases. This study tests the hypothesis that many of the
      behavioral symptoms of FTD (including disinhibition, depressive symptoms,
      carbohydrate craving, and compulsions) will respond to serotonin selective
      reuptake inhibitors (SSRIs). METHOD: Eleven subjects meeting the Lund-Manchester
      clinical, neuropsychological, and neuroimaging criteria for FTD were treated with
      SSRIs (fluoxetine, sertraline, or paroxetine). After 3 months, treatment
      responses for disinhibition, depressive symptoms, carbohydrate craving, and
      compulsions were evaluated prospectively without placebo control. RESULTS: After
      treatment, disinhibition, depressive symptoms, carbohydrate craving, and
      compulsions all showed improvement in at least half the subjects in which they
      had been present. One subject stopped sertraline treatment because of diarrhea,
      while another stopped paroxetine treatment due to increased anxiety. The presence
      of individual behavioral symptoms and also the response of each symptom to SSRIs
      were unrelated to cognitive impairment as measured by baseline Mini-Mental Status
      Examination (.07 < or = p < or = 1.00) [corrected]. CONCLUSION: The behavioral
      symptoms of FTD may improve after treatment with SSRIs. Future neurochemical
      studies and controlled pharmacologic trials may improve available treatments.

PMID- 9184617
TI  - A case of seasonal trichotillomania.

PMID- 9184618
TI  - Clozapine-related speech disturbance.

PMID- 9184619
TI  - Paroxetine-induced anorexia in a patient with bulimia nervosa.

PMID- 9184620
TI  - Novel alternatives and supplements to lithium and anticonvulsants for bipolar
      affective disorder.
AB  - BACKGROUND: Most clinicians are familiar with the traditional anticonvulsants as
      alternatives to lithium in the treatment of bipolar mood disorders. METHOD: This
      review of the English, French, German, and Italian language literature on novel
      treatments, including electroconvulsive therapy, calcium channel blocking agents,
      antipsychotic drugs, benzodiazepines, thyroid hormone, psychosurgery, and two new
      antiepileptic drugs, that have not been studied as extensively as lithium,
      carbamazepine, and valproate but that may have promise as alternatives or
      supplements to traditional thymoleptics when the standard treatments are not
      effective or are poorly tolerated. We searched MEDLINE and PSYCHINFO data bases
      using the keywords bipolar, mood, and/or treatment. We then searched
      bibliographies of articles retrieved by the first strategy. RESULTS: The
      theoretical rationale for each treatment is discussed, followed by a critical
      discussion of the evidence supporting its efficacy. CONCLUSION: The potential
      risks and benefits of each treatment in actual clinical practice are placed in
      perspective.

PMID- 9184622
TI  - Clinical pharmacokinetics of fluvoxamine: applications to dosage regimen design.
AB  - BACKGROUND: The disposition characteristics and pharmacokinetic parameters of
      drugs provide fundamental data for designing safe and effective dosage regimens.
      A drug's volume of distribution, clearance, and the derived parameter, half-life,
      are particularly important, as they determine the degree of fluctuation between a
      maximum and minimum plasma concentration during a dosage interval, the magnitude
      of the steady-state concentration, and the time to reach a steady-state plasma
      concentration upon chronic dosing. Potential drug-drug interactions can be
      predicted with knowledge of affinities for various cytochrome P450 (CYP)
      isozymes. METHOD: The literature was searched for information related to the
      pharmacokinetic properties of fluvoxamine and reports of its involvement in drug
      interactions. RESULTS: The primary pharmacokinetic variables for fluvoxamine have
      been estimated in single and multiple dose studies in animals, health volunteers,
      and patients. Fluvoxamine is well absorbed after oral administration, widely
      distributed in the body, and eliminated with a mean half-life of 15 hours and a
      range from 9 hours to 28 hours. Its disposition is altered in hepatic, but not
      renal, disease. Data from elderly subjects reflect a modest need for dosage
      adjustment in this population. Fluvoxamine produces no active metabolites. The
      specific cytochrome isozymes involved in the hepatic elimination of the drug are
      undefined. Data from studies relating the plasma concentration of fluvoxamine to
      its clinical effects do not support routine plasma concentration monitoring in
      depression or anxiety disorders. Fluvoxamine has prominent affinity for the CYP12
      isozyme, lesser affinity for the CYP3A4 and CYP2C isozymes, and minimal affinity
      for CYP2D6. This profile suggests the need for careful dosage adjustment when
      used together with some drugs that have a narrow therapeutic range in order to
      minimize inhibiting their metabolism. CONCLUSION: Overall, the pharmacokinetic
      profile of fluvoxamine is adequately defined to provide guidelines for developing
      safe and effective dosage regimens for most types of patients.

PMID- 9184623
TI  - Fluvoxamine: a review of the controlled trials in depression.
AB  - Fluvoxamine, a serotonin selective reuptake inhibitor, has been available as an
      antiobsessional agent in the United States since 1995. However, it has been
      utilized as an effective antidepressant for many years in various European
      countries. The controlled trials of fluvoxamine in the pharmacotherapy of
      depression are reviewed. The drug compares well with a variety of other
      antidepressants. It appears safe and well tolerated in daily doses of 50 to 300
      mg. The most common adverse events are gastrointestinal complaints, particularly
      nausea. Initiating pharmacotherapy at lower doses and increasing over the period
      of 1 to 2 weeks minimizes this discomfort.

PMID- 9184621
TI  - Recent advances in depression research: from stress to molecular biology and
      brain imaging.
AB  - This article will heuristically overview some of the more recent
      conceptualizations of the pathogenesis and pathophysiology of major depression as
      well as the functional changes in the central nervous system accompanying its
      successful pharmacotherapy. The neuropharmacology of affective disorders is a
      rapidly advancing field of scientific interest with significant complexity and
      numerous apparently contradictory findings. Within the space limitations of this
      article, some of the relevant newer conceptualizations of the pathophysiology and
      treatment of affective disorders will be summarized. Major concepts to be
      presented include the following: (1) the pathogenesis of affective illness may be
      conceptualized as an interaction between early and current life stressors and
      genetic vulnerability; (2) affective illness has been increasingly conceptualized
      as a potentially chronic progressive illness rather than an intermittent illness
      with full recovery between episodes; (3) affective illness, including its various
      stages, may be readily documented and monitored through changes in functional
      brain imaging; and (4) due to advances in molecular biology technology, there has
      been increasing evidence documenting changes in genetic activity involved in the
      pathogenesis of affective disorders from environmental stressors and/or from
      inherited genetic alterations and of the reversal of these changes accompanying
      successful pharmacotherapy.

PMID- 9184624
TI  - Issues in the assessment of treatment response in panic disorder with special
      reference to fluvoxamine.
AB  - Assessment of treatment response in panic disorder is complicated by the
      multidimensional aspects of panic disorder and agoraphobia, the short-term
      benefits from nonspecific aspects of treatment, and placebo response. Response to
      treatment with psychological and pharmacologic treatments of panic disorder is
      reviewed in this context. The experience of several Phase III studies of
      fluvoxamine in the treatment of panic disorder is examined as an illustrative
      example. When the response to placebo or comparison treatment in a study is high,
      no conclusion can be drawn about the true efficacy of the active treatment.

PMID- 9184625
TI  - Fluvoxamine in the treatment of obsessive-compulsive disorder and related
      conditions.
AB  - The mainstay of the pharmacologic treatment of obsessive-compulsive disorder
      (OCD) is a 10- to 12-week trial of a potent serotonin reuptake inhibitor (SRI) at
      an adequate dose. Double-blind, placebo-controlled trials have established the
      anti-obsessive-compulsive (OC) efficacy of five different SRIs. One of the most
      thoroughly studied of these SRIs is fluvoxamine, the focus of this article.
      Fluvoxamine's pharmacologic and pharmacokinetic properties, its efficacy, and
      guidelines for its clinical use in OCD and related disorders are briefly
      reviewed. Potential drug-drug interactions are discussed and placed in clinical
      perspective. The management of common SRI-induced side effects is also addressed.
      Recent comparative studies suggest that fluvoxamine may be equivalent in efficacy
      to clomipramine, yet better tolerated. Fluvoxamine shows promise in the treatment
      of several so-called OC-spectrum disorders, but additional controlled trials are
      needed.

PMID- 9184626
TI  - Role of serotonin drugs in the treatment of social phobia.
AB  - Social phobia is a common anxiety disorder that is underdiagnosed and
      undertreated. To date, three classes of serotonin drugs have been used to treat
      patients suffering from social phobia. These include the serotonin selective
      reuptake inhibitors (SSRIs), the partial 5-HT1A agonist buspirone, and the 5-HT3
      antagonist ondansetron. Although none of the serotonin agents have yet been
      directly compared with the gold standard monoamine oxidase inhibitor phenelzine
      or the high potency triazolobenzo-diazepines alprazolam or clonazepam, the SSRIs,
      as a class, appear to be clinically useful agents. Further studies using larger
      sample sizes and double-blind methodology are needed to clarify the role of
      serotonin drugs in the treatment of social phobia.

PMID- 9184627
TI  - A monoclonal antibody to the ligand-binding domain of the neurokinin 1 receptor
      (NK1-R) for the neuropeptide substance P.
AB  - Monoclonal antibodies to the binding site of the NK1 receptor for the
      neuropeptide substance P were produced in mice using the complementary or
      antisense peptide methodology. Among several anti-peptide monoclonal antibodies,
      we selected the mAb12 antibody which specifically crossreacted, through its
      paratope, with a binding site present on membranes from rat parotid gland cells,
      with an affinity close to 2 x 10(-7) M and with membranes from CHO cells
      expressing human brain NK1 receptors. Immunocytochemical investigations using
      mAb12 revealed immunostaining whose distribution in the dorsal horns of rat
      spinal cord fits well with the known location of NK1 receptors. In both
      biochemical and immunocytochemical experiments, the competition occurring between
      the antibody and substance P, or a substance P-protein conjugate, indicates that
      mAb12 recognizes a membrane epitope located at or near the substance P binding
      domain on the NK1 receptor. Immunization of mice with mAb12 led to the production
      of specific anti-substance P antibodies, again suggesting that mAb12 shares
      common structural features with the neuropeptide. This monoclonal antibody can
      now be used in further biochemical or cytochemical characterizations of NK1
      receptors. Owing to its fine specificity, mAb12 could also serve as a molecular
      model for designing peptides, possibly displaying pharmacological properties in
      the various processes in which substance P is involved, e.g. immunomodulation,
      inflammation or chronic pain.

PMID- 9184628
TI  - Inhibition of gamma interferon synthesis by catecholamines.
AB  - In vitro incubation of Listeria monocytogenes immune spleen cells in the presence
      of the catecholamines epinephrine or norepinephrine inhibited the gamma
      interferon (IFN-gamma) synthesis induced by the mitogen PHA, in a manner that
      appeared to be concentration dependent. Moreover, the inhibitory effect of both
      catecholamines epinephrine and norepinephrine on the synthesis of IFN-gamma was
      prevented by incubating immune spleen cells in the presence of propranolol, a
      beta adrenergic antagonist agent.

PMID- 9184629
TI  - Results of a phase I clinical trial of a T-cell receptor peptide vaccine in
      patients with multiple sclerosis. I. Analysis of T-cell receptor utilization in
      CSF cell populations.
AB  - To identify a panel of multiple sclerosis patients (MS) for a phase I clinical
      trial of a T-cell receptor (TCR) peptide vaccine we characterized the T-cell
      populations present in the cerebrospinal fluids (CSF) of a large group of
      patients with respect to surface phenotype and state of activation, TCR beta
      chain utilization, features of the CDR3 junctional region, the extent of
      clonality and persistence of selected clonotypes over time. These CSF cell
      populations consist of approximately 60% CD4+ T-cells, half of which bear IL-2
      receptors, indicating these activated T-cells may be part of the pathogenic
      process in MS. When these activated CD4+ T-cells were selectively expanded in IL
      2/IL-4 supplemented cultures, an over-representation of several TCRV beta
      families was noted in 39/47 patients, the most frequent being V beta 6.5, V beta
      6.7, V beta 2, V beta 5 and V beta 4. Biased expression of various members of the
      V beta 6 family was seen in 21 of this group of 39 patients. Clonal analysis of
      TCR beta 6 CDR3 sequences, revealed two notable features: clonal dominance and
      clonal persistence. CSF cells from two-thirds of MS patients contained a dominant
      clone comprising 50% or more of sequences and the same patient-specific clone
      could be shown to persist for up to 18 months. This clonal prevalence and over
      representation of V beta 6+TCR raises the possibility that immunization with a V
      beta 6 peptide vaccine may produce a regulatory immune response leading to a
      clinical benefit.

PMID- 9184630
TI  - Results of a phase I clinical trial of a T-cell receptor vaccine in patients with
      multiple sclerosis. II. Comparative analysis of TCR utilization in CSF T-cell
      populations before and after vaccination with a TCRV beta 6 CDR2 peptide.
AB  - We report here the results of a phase I trial of a T-cell receptor (TCR) V beta 6
      CDR2 region peptide vaccine in 10 patients with multiple sclerosis who showed
      biased over-representations of V beta 6 mRNA among T-cells in their cerebrospinal
      fluids (CSF). One group of 5 patients was immunized twice during a four week
      period with 100 micrograms of the TCRV beta 6 peptide 39-LGQGPEF LTYFQNEAQLEKS-58
      emulsified in incomplete Freund's adjuvant (IFA); the second group of 5 MS
      patients received 300 micrograms of the same peptide in IFA over a similar time
      period. Patients were monitored for adverse events, immunogenicity of the peptide
      and changes in their CSF T-cell populations. The results indicate that this
      peptide was immunogenic (T-cell proliferation assays and recall DTH responses) in
      some of the patients, although none of the immunized patients produced detectable
      anti-peptide antibodies. More importantly, we show that the 5 patients treated
      with higher doses of the vaccine displayed a slight decrease in CSF cellularity,
      a lack of growth of CSF cells in cytokine supplemented expansion cultures that
      implies a significant absence of a subset of activated CD4 T-cells and a marked
      diminution in V beta 6 mRNA levels among T-cells in these cultures. By
      comparison, in 5 patients receiving the lower dosage of the vaccine, CSF
      cellularity was the same or slightly increased over pre-vaccination levels, CSF
      cells from 1 patient failed to grow in expansion cultures and cultured CSF cells
      from 2 patients underwent a change from an oligoclonal V beta 6 pattern to one
      that was more polyclonal. These results justify a more through exploration of the
      use of TCR peptide vaccines as a possible therapeutic treatment for MS.

PMID- 9184631
TI  - Pituitary hormones modulate cell-cell interactions between thymocytes and thymic
      epithelial cells.
AB  - The thymic microenvironment plays a key role in the intrathymic T-cell
      differentiation. It is composed of a tridimensional network of epithelial cells
      whose physiology is controlled by extrinsic circuits such as neuroendocrine axes.
      Herein we show that the expression of extracellular matrix ligands and receptor
      by cultured thymic epithelial cells is upregulated by prolactin (PRL) and growth
      hormone (GH), the latter apparently occurring via insulin-like growth factor I
      (IGF-I). Thymocyte release from the lymphoepithelial complexes, thymic nurse
      cells, as well as the reconstitution of these complexes are enhanced by PRL, GH
      or IGF-I. Treatment of a mouse thymic epithelial cell line with these hormones
      induced an increase in thymocyte adhesion, an effect significantly prevented in
      the presence of antibodies to fibronectin, laminin or respective receptors VLA-5
      and VLA-6. Our data suggest that the in vitro changes in thymocyte/thymic
      epithelial cell interactions induced by pituitary hormones are partially mediated
      by the enhancement of extracellular matrix ligands and receptors.

PMID- 9184632
TI  - Preferential recognition of synthetic peptides from HTLV-I gp21 envelope protein
      by HLA-DRB1 alleles associated with HAM/TSP (HTLV-I-associated
      myelopathy/tropical spastic paraparesis).
AB  - To determine CD4+ T-cell epitopes of HTLV-I-envelope protein recognized by the
      HLA alleles associated with HAM/TSP, we established 20 CD4+ T-cell lines from
      peripheral blood mononuclear cells (PBMCs) of naive healthy donors using a panel
      of synthetic peptides spanning the entire length of HTLV-I-envelope proteins,
      gp46 and gp21. We quantitated the precursor frequencies of HTLV-1-envelope
      specific CD4+ T-cells and analyzed epitope specificity in the context of HLA
      alleles. The precursor frequencies ranged from 3.0 to 10.6 per 10(7) PBMCs in the
      naive healthy donors. The CD4+ T-cell epitopes of HTLV-I-envelope protein were
      clustered in amino acids 76 to 90, 136 to 160, 171 to 185 and 196 to 210 of gp46,
      and in amino acids 366 to 400 and 436 to 485 of gp21. The CD4+ T-cell epitopes of
      gp21 were preferentially recognized by HLA-DRB1 0101 and 1502 which were known to
      be associated with HAM/TSP. Thus, it was suggested that HTLV-I gp21 might contain
      the major CD4+ T-cell epitopes recognized by HLA-DRB1 alleles of HAM/TSP.

PMID- 9184633
TI  - Expression of CD23 in the germinal center of thymus from myasthenia gravis
      patients.
AB  - In order to investigate a pathogenic role of germinal centers which appear in the
      hyperplastic thymus of myasthenia gravis (MG) patients, we performed an
      immunohistochemical study using various monoclonal antibodies including CD23. In
      contrast with tonsilar germinal centers from non-MG individuals, CD23 was
      strongly and diffusely expressed in the whole area of germinal centers of MG
      thymi, including the outer zone. In addition, we measured the serum level of
      soluble CD23 (sCD23) in MG patients at various clinical stages. The high serum
      sCD23 levels, which were noted in the unthymectomized patients, fell to within
      normal range over 5 years after thymectomy, and the decline of serum sCD23
      correlated well with clinical improvement. CD23 is thought to be responsible for
      preventing unselected germinal center B cells from entering apoptosis and, in
      turn, leads to the survival of auto-reactive B cell clones.

PMID- 9184634
TI  - Apolipoprotein E suppresses glial cell secretion of TNF alpha.
AB  - Apolipoprotein E (apoE) is a 299 amino acid protein with multiple biological
      functions. Initially described in the context of cholesterol metabolism, apoE
      also has immunomodulatory properties and recent evidence has implicated a role
      for apoE in neurological disease. One possibility is that apoE, which is the
      predominant apolipoprotein produced intra-axially, may modify the CNS response to
      acute and chronic injury. We prepared mixed neuronal-glial cultures from apoE
      deficient mouse pups and measured secretion of TNF alpha after stimulation with
      lipopolysaccharide (LPS) in the presence and absence of human recombinant apoE3
      and E4. We demonstrate that preincubation with apoE blocks glial secretion of TNF
      alpha in a dose-dependent manner. This effect is independent of any direct effect
      of apoE on cell viability and is greatest when apoE is preincubated with the cell
      culture for 24 h.

PMID- 9184635
TI  - Pulsed intravenous methylprednisolone therapy for inflammatory myopathies:
      evaluation of the effect by comparing two consecutive biopsies from the same
      muscle.
AB  - To examine the effect of pulsed intravenous methylprednisolone (IVMP) on
      polymositis (PM) and dermatomyositis (DM), two biopsies were taken from the same
      muscle before and after IVMP in one case each of PM and DM. After IVMP, numerous
      muscle fibers were seen undergoing regeneration. Among all subsets of
      infiltrating cells that decreased in number, macrophages in the perivascular area
      decreased markedly. Also conspicuous was decrease of CD8+ cells in the endomysium
      in PM and that of B-cells in the perivascular area in DM. Among infiltrating
      cells, frequency of those which expressed the signal transducers and activators
      of transcription 1 (STAT-1) fell considerably, but remained still abnormally
      high. Regions on the endothelial cells of blood vessels that expressed MHC
      antigens and intercellular adhesion molecules 1 (ICAM-1) also decreased but
      remained more widespread than normal. These results agreed with the favorable
      clinical effect of IVMP, but showed that many of the immunological parameters
      remained abnormal.

PMID- 9184637
TI  - In vitro modulation of human, autoreactive MBP-specific CD4 + T-cell clones by
      cyclosporin A.
AB  - Cyclosporin A (CsA) is a potent immunosuppressant affecting many components of
      cellular and humoral immunity. Its main action probably results from inhibition
      of T-lymphocyte activation and interference with secretion of cytokines like IL
      2, IL-4, IFN-gamma and TNF-alpha. Correspondingly, CsA has beneficial effects on
      the course of several autoimmune diseases thought to be mediated by T
      lymphocytes, including a mild effect on multiple sclerosis. We exposed CD4 +
      cytotoxic T-lymphocytes specific for myelin basic protein, a putative target
      autoantigen in MS, to CsA in vitro, and determined the drug's effects on
      proliferation, expression of high affinity IL-2R, secretion of the
      proinflammatory cytokines IFN-gamma and TNF-alpha as well as on the secretion of
      the chemokines MIP-1 alpha and MIP-1 beta. In all instances, we observed a
      partial to complete inhibition. In contrast, the response of activated cells to
      IL-2 was resistant to CsA. Our observations are in line with results obtained in
      different experimental systems. The discrepancy between the profound inhibition
      of T-cells and the modest therapeutic effects on MS is discussed.

PMID- 9184636
TI  - Selective expression of adhesion molecules on human brain microvascular
      endothelial cells.
AB  - Human microvascular endothelial cells were isolated from children's brain and
      examined for their morphological characteristics and upregulation of cell
      adhesion molecules in response to TNF alpha. Our human brain microvascular
      endothelial cells (HBMEC) were positive for factor VIII-Rag, carbonic anhydrase
      IV, Ulex Europeus Agglutinin I, took up fluorescently labeled acetylated low
      density lipoprotein and expressed gamma glutamyl transpeptidase, demonstrating
      their brain endothelial cell characteristics. Upon treatment with TNF alpha. VCAM
      and ICAM but little ELAM was expressed on HBMEC, while VCAM, ICAM and ELAM were
      clearly evident on HUVEC. This selective expression of cell adhesion molecules
      was also demonstrated by in situ stimulation of brain tissues. In conclusion,
      microvascular endothelial cells from childrens brains display selective
      expression of cell adhesion molecules, which differ from macrovascular
      endothelial cells. This may have consequences for leukocyte trafficking into the
      central nervous system.

PMID- 9184638
TI  - Detection of CSF-specific oligoclonal antibodies to recombinant JC virus VP1 in
      patients with progressive multifocal leukoencephalopathy.
AB  - The intrathecal synthesis of antibodies against recombinant VP1, the major
      structural protein of JC virus (JCV), was studied in 18 patients with progressive
      multifocal leukoencephalopathy (PML) and in 31 patients with various neurological
      disorders. Two methods were used, the calculation of an antibody specific index
      (ASI) on one hand and an antigen-driven immunoblotting for the detection of
      oligoclonal antibodies on the other. Most PML patients displayed an elevated (>
      1.5) ASI (78%) and anti-VP1 oligoclonal antibodies restricted to the
      cerebrospinal fluid (55%). Only two other patients (one case each of multiple
      sclerosis and of neuroborreliosis) also showed an intrathecal synthesis of anti
      VP1 oligoclonal antibodies, likely as a result of a 'polyspecific' reaction
      within the central nervous system.

PMID- 9184639
TI  - Permeability of the blood-brain and blood-spinal cord barriers to interferons.
AB  - Interferons (IFNs) are cytokines that produce effects in the CNS even though
      their production occurs mainly in the periphery. Direct passage of IFNs from
      blood to CNS could be an important route by which circulating IFNs exert their
      central effects. In this report, we characterize the pharmacokinetics of the
      passage of IFNs through the blood-brain and blood-spinal cord barriers in four
      separate regions: whole brain and the cervical, thoracic and lumbosacral segments
      of the spinal cord. We found that the spinal cord had greater permeability to
      IFNs than did the brain. For each corresponding region, the permeability to IFN
      alpha was higher than that to IFN gamma. Capillary depletion after cardiac
      perfusion showed that most of the injected IFN was not entrapped by the
      vasculature but entered the parenchyma of the brain. HPLC showed that most of the
      IFN gamma entered in intact form. The passage of radioactively labeled IFN gamma
      into the brain and cervical spinal cord was saturated by a low dose of unlabeled
      IFN gamma, while passage into the thoracic and lumbosacral spinal cord was not
      saturated. In contrast, for another cytokine, tumor necrosis factor alpha (TNF
      alpha), a saturable transport system was present in distal spinal cord as well as
      the brain. The results show that IFNs and TNF alpha can enter the CNS from the
      periphery but with regional differences.

PMID- 9184640
TI  - Failure of intravenous immunoglobulin (IVIg) therapy in experimental autoimmune
      neuritis (EAN) of the Lewis rat.
AB  - Experimental autoimmune neuritis (EAN) is an animal model for Guillain-Barre
      syndrome (GBS). Intravenous immunoglobulins (IVIg) are an effective treatment for
      GBS, but their mechanism of action is not well understood. Here we tested whether
      IVIg treatment, a potent modulator of proinflammatory assaults, reduces
      inflammation in EAN. The evaluation of IVIg treatment failed to demonstrate a
      salutary effect in different models of EAN. IVIg appears not to suppress the
      acute inflammatory insult on the peripheral nerve, but may have beneficial long
      term effects not looked for in the present investigation.

PMID- 9184641
TI  - Enriched immune-environment of blood-brain barrier deficient areas of normal
      adult rats.
AB  - The circumventricular organs (CVOs) in the brain are without a blood-brain
      barrier (BBB) and as such directly exposed to blood plasma constituents and blood
      borne pathogens. In light of previous studies showing discrepancies regarding the
      immunocompetence of these organs, we initiated the present study to provide a
      comprehensive immunohistochemical analysis of the cellular expression of immune
      associated antigens within the pineal gland, area postrema and the subfornical
      organ. In all CVOs, subpopulations of cells morphologically similar to complement
      receptor type 3 immunoreactive microglial/macrophage cells expressed major
      histocompatibility complex (MHC) class II antigen, leucocyte common antigen
      (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the
      MHC class II antigen expressing cells could be grouped into a major population of
      classical parenchymal and perivascular ramified microglial cells and a minor
      population presenting itself as scattered or small groups of rounded macrophage
      like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was
      preferentially expressed by macrophage-like cells. MHC class I antigen was
      expressed by the vascular endothelium in both BBB-protected and BBB-deficient
      areas and was additionally present as a lattice-like network throughout the BBB
      deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of
      the brain besides being constantly surveyed by blood-borne macrophages, possess
      an intrinsic immune surveillance system based on resting and activated microglial
      cells, which may function as a non-endothelial, cellular barrier against blood
      borne pathogens.

PMID- 9184642
TI  - Constitutive expression of costimulatory molecules by human microglia and its
      relevance to CNS autoimmunity.
AB  - Human microglia constitute the primary residential antigen presenting cells
      (APCs) in the central nervous system (CNS) and have the capacity of activating
      myelin reactive T-cells. T-cell activation requires two signals: first is the
      interaction of the T-cell receptor with the MHC-antigen complex and, secondly,
      contact of the CD28/CTLA4 T-cell surface molecules with the B7 family of
      costimulatory molecules on the APCs. We have previously shown high expression of
      B7.1 in early multiple sclerosis (MS) plaques, suggesting that acute T-cell
      mediated CNS inflammation may require local B7.1 upregulation. We have now
      examined the expression of B7.1 and B7.2 costimulatory molecules on resting ex
      vivo human microglia isolated directly from biopsy specimens. We found
      constitutive expression of B7.2 but not B7.1 on resting microglia, suggesting
      that B7.2 expression may lead to downregulation of pro-inflammatory Th1 T-cell
      responses in the normal brain.

PMID- 9184643
TI  - Protein kinase A-dependent IL-6 production induced by calcitonin in human
      glioblastoma A172 cells.
AB  - In human glioblastoma A172 cells, interleukin-6 (IL-6) production was induced by
      interleukin-1 beta (IL-1 beta) and dibutyryl cyclic AMP. These cells have been
      shown to induce IL-6 production via a cAMP-protein kinase A system. Since
      calcitonin (CT) and calcitonin gene-related peptide (CGRP) are known to increase
      cAMP accumulation in murine and rat astrocytes, we examined whether these
      neuropeptides induced IL-6 production in A172 cells. Human CT and human CGRP
      increased IL-6 production and cAMP accumulation in a dose-dependent manner. A
      specific protein kinase A inhibitor, H-89, inhibited both CT- and CGRP-induced IL
      6 production. CT and CGRP have been shown to cross-react with each other. To
      exclude the possibility of this cross-reactivity, we studied the additive effects
      of CT and CGRP and the inhibitory effects of specific inhibitors. When 100 nM CT
      was added, cAMP accumulation stimulated by 10 nM CGRP (the maximal dose) was
      increased. CGRP (8-37), a specific CGRP receptor inhibitor, inhibited cAMP
      accumulation and IL-6 production induced by CGRP, but did not inhibit these
      effects when they were induced by CT. Salmon CT (8-32), a specific inhibitor of
      the CT receptor, inhibited cAMP accumulation induced by CT, but did not inhibit
      the effect induced by CGRP. These results demonstrated that CT can induce IL-6
      production via cAMP accumulation and the effects of CT are mediated via its own
      receptors.

PMID- 9184644
TI  - Long-term regulation of opioid receptors in neuroblastoma and lymphoma cell
      lines.
AB  - Long-term regulation of opioid binding was studied in the human neuroblastoma NMB
      and in the murine lymphoma R1.1 and R1.EGO cell lines. Binding was down-regulated
      following prolonged exposure to opioid agonists and up-regulated following
      exposure to antagonist. Down-regulation was inhibited by the metabolic blocker
      sodium-azide and by the protein kinase H-7. Up-regulation was blocked by the
      protein and mRNA synthesis blockers cycloheximide, alpha-amanitin and actinomycin
      D. A significant difference was found between the response of neuronal and immune
      cells to ethanol exposure: while opioid binding in neuroblastoma culture
      underwent a pronounced (75%) up-regulation, no effect of ethanol on opioid
      receptors in lymphoma cultures was detected. The described cell lines present an
      excellent experimental model to study long-term regulation of opioid receptors in
      the nervous and immune systems and to elucidate the biological effects of chronic
      use of opiates and alcohol.

PMID- 9184645
TI  - The apoptotic death of neuroblastoma cells caused by serum from patients with
      insulin-dependent diabetes and neuropathy may be Fas-mediated.
AB  - Immunoglobulins from patients with diabetic neuropathy are toxic to neuroblastoma
      cells. The cell death has characteristics of apoptosis: condensed chromatin,
      shrunken cytoplasm, elevation of [Ca2+]i and DNA fragmentation. N1E-115 cell
      membranes contain Fas, a regulator of apoptosis that recently has been shown to
      be involved in pancreatic beta-cell destruction leading to diabetes. Fas-specific
      antibodies bind to the surface of N1E-115 cells and induce apoptosis. Serum from
      patients with diabetic neuropathy block Fas-antibody binding. We conclude that
      sera from patients with diabetic neuropathy contain an activator of Fas-regulated
      apoptosis that may contribute to the pathogenesis of diabetic neuropathy.

PMID- 9184646
TI  - Identification of neurotensin-related peptides in human thymic epithelial cell
      membranes and relationship with major histocompatibility complex class I
      molecules.
AB  - This study shows the expression at the cell surface of human thymic epithelial
      cells (TEC) of a neurotensin (NT)-like immunoreactivity. NT radio-immunoassay
      (RIA) revealed that cultured human TEC contain +/-5 ng immunoreactive (ir)
      NT/10(6) cells, of which 5% is associated with plasma cell membranes. HPLC
      analysis of NT-ir present in human TEC showed a major peak of NT-ir corresponding
      to NT1-13. NT-ir was not detected in the supernatant of human TEC cultures. Using
      an affinity column prepared with a anti-MHC class I monoclonal antibody, NT-ir
      related peptides were retained on the column and eluted together with MHC class I
      related proteins. According to the elution time on HPLC of these peptides, they
      correspond to intact NT1-13, as well as to smaller fragments of NT1-13.

PMID- 9184647
TI  - Interleukin-10 downregulates the intracerebral immune response in chronic
      Toxoplasma encephalitis.
AB  - The expression of the immunosuppressive cytokine interleukin (IL)-10 in the
      normal and Toxoplasma gondii-infected murine brain was analysed.
      Microglia/macrophages expressed IL-10 at the mRNA and protein level in the normal
      brain. In Toxoplasma encephalitis (TE), CD4+ and CD8+ T-cells also contributed to
      the upregulated IL-10 production. Neutralization of endogenous IL-10 in chronic
      TE reduced the intracerebral parasitic load and increased the number of immune
      cells and the production of protective cytokines. These findings indicate that
      intracerebral expression of IL-10 interferes with the immune response in TE and
      may contribute to parasite persistence in the brain.

PMID- 9184649
TI  - TNF alpha in cerebrospinal fluid of meningitis patients reduces astrocytes
      membrane potential.
AB  - During inflammatory CNS diseases cytokines are released into the cerebrospinal
      fluid (CSF). Astrocytes which are target cells for cytokines also contribute
      importantly to undisturbed neuronal function e.g. by maintaining local ion
      homeostasis. The effects of CSF from patients with septic (CSF-SM) and aseptic
      (CSF-ASM) meningitis on electrophysiological membrane properties of cultured rat
      cortical astrocytes were investigated. Astrocytes significantly depolarized from
      a membrane potential of -75.6 +/- 2.3 to -47.4 +/- 6.2 mV in CSF-SM (n = 8). 12
      of 18 CSF-ASM also induced a depolarization. The depolarization of astrocytes was
      inhibited by a neutralizing anti-TNF alpha antibody, indicating that the cytokine
      TNF alpha initiates the depolarization.

PMID- 9184648
TI  - Linomide-induced suppression of experimental autoimmune neuritis is associated
      with down-regulated macrophage functions.
AB  - Experimental autoimmune neuritis (EAN) is a T-cell mediated autoimmune disease of
      the peripheral nervous system, in which macrophages and T-cells feature
      prominently in nerve lesions. EAN represents a counterpart to Guillain-Barre
      syndrome in humans. In the present study, we investigated the in vitro and in
      vivo effects of Linomide (LS-2616, quinoline-3-carboxamide), a synthetic
      immunomodulatory compound, on macrophages in relation to EAN. Linomide strongly
      suppressed IFN-gamma and lipopolysaccharide (LPS)-induced IL-1 beta, TNF-alpha
      and IL-6 mRNA expression in macrophages in vitro as demonstrated by in situ
      hybridisation. Linomide administered daily subcutaneously from the day of
      inoculation completely prevented the development of clinical symptoms of EAN.
      Linomide administered from day 9 post immunisation (p.i.) significantly
      suppressed clinical EAN. Macrophages from Linomide-treated EAN rats showed
      decreased IL-1 beta, TNF-alpha and IL-6 mRNA expression in response to IFN-gamma
      and LPS. LPS-induced nitric oxide production by macrophages was also suppressed
      by Linomide in vitro. Linomide, however, does not affect macrophage death and
      release of lactate dehydrogenase. We conclude that Linomide may exert its actions
      in EAN and perhaps also in other autoimmune disease models, by suppressing
      macrophage functions.

PMID- 9184651
TI  - The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by
      ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion.
AB  - Ischemic brain injury is exacerbated by leukocyte infiltration and formation of
      vasogenic edema. In this study we demonstrate that intercellular adhesion
      molecule-1 (ICAM-1) is dramatically (3 to 15-fold) up-regulated in human
      cerebromicrovascular endothelial cells (HCEC) by a 16 h exposure to the cytokine,
      IL-1 beta (50-200 u/ml), the phorbol ester, TPA (1-100 nM), or by simulated in
      vitro ischemia/reperfusion. These treatments also significantly increased the
      adhesion of allogeneic neutrophils to HCEC monolayers. Both IL-1 beta- and TPA
      induced expression of ICAM-1 and increased neutrophil adhesion to HCEC were
      inhibited by the transcriptional inhibitor, actinomycin D (AcD; 1-10
      micrograms/ml), and by an anti-ICAM-1 antibody (ICAM-1 Ab). By contrast, ischemia
      induced neutrophil adhesion was only slightly affected by AcD and ICAM-1 Ab
      alone, but it was abolished by the combination of anti-ICAM-1 and anti-CD18
      antibodies. The increase in surface expression of ICAM-1 and neutrophil adhesion
      by IL-1 beta, TPA and ischemia were significantly reduced by the cyclo-oxygenase
      (COX) inhibitors, indomethacin (100-300 microM) and dexamethasone (10-50 microM).
      These results indicate that ICAM-1 expression in HCEC can lead to enhanced
      neutrophil adhesion and that COX activation in HCEC likely plays a role in the
      processes by which leukocyte adhesion and recruitment take place in the brain
      during inflammation and ischemia in vivo.

PMID- 9184650
TI  - Occurrence and clinical relevance of an interleukin-4 gene polymorphism in
      patients with multiple sclerosis.
AB  - An epistatic gene interaction has been advocated to explain disease
      susceptibility in multiple sclerosis (MS). Cytokine genes are possible candidates
      due to the central role played by cytokines in the regulation of the immune
      mediated pathogenetic process leading to central nervous system demyelination in
      these patients. Since interleukin (IL)-4 gene polymorphisms have been associated
      with immune-mediated diseases, we have analysed the relationship between a
      variable number of tandem repeat polymorphism of the IL-4 gene and clinical and
      physiological features of 256 sporadic MS patients and 146 healthy controls.
      Genotype frequencies were similar between the MS group and healthy controls.
      However, in MS patients a positive and significant correlation (r = 0.91; p <
      0.001) was found between the carriage rate of the IL-4 B1 allele (from 0.21 to
      0.36) and age of disease onset. No association was found between IL-4 alleles and
      disease progression, sex or ethnic background of the patients. Our results show
      that the IL-4 B1 allele is associated with late onset of MS and therefore might
      represent a modifier of age of onset rather than a susceptibility factor for
      patients with MS.

PMID- 9184652
TI  - Establishment of an efficient enzyme-linked immunosorbent assay for the
      determination of human choline acetyltransferase.
AB  - A specific and sensitive two-side enzyme-linked immunosorbent assay (sandwich
      ELISA) was established for the reliable quantification of human brain and
      placental choline acetyltransferase (ChAT). In contrast to the radiometric assay
      developed by Fonnum, which is widely used for the measurement of enzyme activity,
      the sandwich-ELISA particularly recognized inactivated forms of the antigen. In
      the assay, affinity-purified polyclonal synthetic peptide antibodies adsorbed to
      the polystyrene surface of the microtiter plate were employed as capture reagent.
      Based on standard peroxidase protocols, immobilized ChAT was detected using
      monoclonal antibodies raised against human placental ChAT. By use of this ELISA,
      ChAT was determined at various purification stages of the enzyme, in body fluids,
      during recovery experiments and in sera of patients with severe brain damage.

PMID- 9184653
TI  - Central nervous system cytokine mRNA expression following Theiler's murine
      encephalomyelitis virus infection.
AB  - DA strain of Theiler's murine encephalomyelitis virus (TMEV) produces a biphasic
      disease with an initial self-limited acute gray matter polioencephalomyelitis in
      all strains of mice followed by, in the case of certain susceptible strains of
      mice, a chronic inflammatory demyelination of the spinal cord with a persistent
      virus infection. A pathogenic role for T-helper 1 (Th1) cells during the
      demyelinating phase of disease has been proposed. We characterized the cytokine
      mRNA expression in the brain and spinal cord of susceptible and resistant strains
      of mice during the early encephalomyelitic disease and the late demyelination,
      using a semi-quantitative reverse transcription-polymerase chain reaction (RT
      PCR) assay. At the time of the encephalomyelitis, both resistant and susceptible
      mice expressed proinflammatory cytokine mRNAs followed by T-cell derived mRNAs;
      susceptible mice expressed more IL-12 p40 mRNA than resistant mice. During this
      early disease, there was no significant difference in Th1 cytokine mRNA
      expression in the brain and spinal cord among the four strains and relatively
      little Th2 type cytokine upregulation above levels seen in mock-infected
      controls. During the late demyelinating disease, susceptible but not resistant
      mice had evidence of viral genome and a continuous expression of Th1 type
      cytokine mRNAs. The expression of Th2 cytokine mRNAs varied among the different
      strains and did not correlate with susceptibility or resistance. The results
      indicate the complexity of cytokine mRNA expression following TMEV infection and
      the dependence of the expression on disease pathology, the time following
      infection and the genetics of the host.

PMID- 9184654
TI  - Mast cell interactions with the nervous system: relationship to mechanisms of
      disease.
AB  - In summary, mast cell interactions in the nervous system are relevant to both
      physiological processes (i.e. reproduction) and pathologic states (i.e.
      inflammatory demyelination, painful disorders, toxic and metabolic disease, and
      tumor angiogenesis). Their physiologic roles may contribute to gender-related
      vulnerability to inflammatory disease and may modulate sensitivity to pain. Mast
      cells are universally involved in tissue repair and they release and respond to
      trophic factors such as NGF. These cells also produce and react to cytokines, and
      thus appear to play a role in tissue degeneration as well as repair. In certain
      neurological diseases, i.e. multiple sclerosis and Guillain-Barre syndrome, the
      ability of mast cell proteases to degrade specific myelin proteins suggests that
      these cells are agents, rather than bystanders, in the demyelinative process.
      Even more intriguing is their recently identified capacity to process bacterial
      antigen as efficiently as activated macrophages, suggesting that a more critical
      role than previously suspected might be considered for mast cells in CNS and PNS
      demyelination. In experimental metabolic disorders such as galactose intoxication
      and thiamine deficiency, mast cells appear to play a pathogenic role. Thus, in
      galactose intoxication, altered BNB vascular permeability occurs in conjunction
      with mast cell proliferation and degranulation, while in thiamine deficiency,
      increased histamine levels have been reported in the rat thalamus (79) and are
      associated with cell death and proliferation as well as mast cell degranulation
      (Powell and Langlais, unpublished observations). Structural interactions between
      mast cells and a variety of other cells have been observed, as well as close
      approximation of mast cells to nerve endings in tissues in which mast cells are
      especially active. Due to their paracrine nature, mast cells can modulate events
      in their microenvironment through explosive degranulation, piecemeal
      degranulation, or "transgranulation" as they insert granules into neighboring
      cells. Lastly, these cells play specific roles in reparative processes, e.g.
      angiogenesis, and are active in neoplastic states, including von Recklinghausen's
      disease (neurofibromatosis). Their involvement may have been underestimated in
      neuropathological studies, to date, by a reliance on staining techniques that are
      inadequate for identifying degranulated and therefore activated mast cells (4).
      More exacting histochemical and immunostaining procedures will help to fully
      realize the extent of their participation in physiological and pathological
      processes.

PMID- 9184655
TI  - High IL-6 and low IL-10 in the central nervous system are associated with
      protracted relapsing EAE in DA rats.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated,
      inflammatory demyelinating disease of the central nervous system (CNS) that
      serves as a model for multiple sclerosis (MS). The mechanisms behind differences
      in clinical course of EAE in different rat strains have not been defined. We
      induced acute EAE in Lewis rats and protracted relapsing EAE (PR-EAE) in DA rats
      and examined mRNA expression of IL-1 beta, IL-6, IL-10, IL-12, and TNF-beta in
      brain tissue sections, cerebrospinal fluid (CSF) cells, and lymph node cells. IL
      1 beta, IL-12 and TNF-beta mRNA expression in brain tissue sections appeared
      early and peaked at the height of clinical signs in both acute and PR-EAE,
      consistent with a disease-promoting role for these cytokines. High levels of IL-6
      mRNA-expressing cells were present in CNS and lymph node cells in PR-EAE, while
      almost absent in acute EAE. In contrast, IL-10 was very low in PR-EAE but
      strongly expressed in acute EAE, in particular during clinical recovery.
      Regulatory changes of IL-6 and IL-10 both systemically and within the CNS, but
      with temporal differences between compartments, seem pivotal for development of
      PR-EAE in DA rats. These findings could have relevance for pathogenesis and
      treatment of MS.

PMID- 9184656
TI  - Interleukin (IL)-1 beta and IL-1 beta mRNA expression in normal and diseased
      skeletal muscle assessed by immunocytochemistry, immunoblotting and reverse
      transcriptase-nested polymerase chain reaction.
AB  - To confirm the production of IL-1 beta and to optimize detection and
      semiquantitation of IL-1 beta mRNA by polymerase chain reaction (PCR) techniques
      in skeletal muscle tissue, immunocytochemistry, immunoblotting and several
      procedures of RNA extraction and reverse transcription (RT)-PCR amplification
      were used on muscle samples from 12 patients with conditions associated with
      local production of IL-1 beta (AZT myopathy: 6 patients; sarcoid myopathy: 6
      patients) and from 9 patients with normal muscle used as controls. Abundant IL-1
      beta immunoreactivities, corresponding to both pro IL-1 beta and mature IL-1 beta
      as assessed by immunoblotting, were observed in all diseased muscles, either in
      inflammatory cells (sarcoid myopathy) or in atrophic muscle fibers (AZT
      myopathy). Acid guanidinium isothiocyanate phenol-chloroform extraction of RNA
      appeared less efficient for IL-1 beta mRNA detection by RT-PCR than proteinase K
      digestion followed by phenol-chloroform extraction. Even using the latter
      procedure, RT-single PCR for IL-1 beta mRNA was puzzlingly negative in all cases
      but one; in contrast, RT-nested PCR specified by DNA enzyme immunoassay yielded
      detection of IL-1 beta mRNA in all diseased muscles and in occasional controls,
      including the expected PCR product of 391 bp, but also another product of 935 bp,
      corresponding to IL-1 beta mRNA with unsplicing of the fourth intron. Semi
      quantitative PCR showed that production of IL-1 beta mRNA was higher in sarcoid
      myopathy than in AZT myopathy, and in AZT myopathy than in controls. In
      conclusion, IL-1 beta expression can be reliably studied using
      immunocytochemistry, but assessment of IL-1 beta mRNA production in muscle tissue
      requires optimized extraction and RT-PCR procedures.

PMID- 9184657
TI  - Multiple sclerosis: altered expression of 70- and 27-kDa heat shock proteins in
      lesions and myelin.
AB  - Recent studies have implicated heat shock proteins (HSP) in the pathogenesis of
      the multiple sclerosis (MS) lesion. Expression of the 73 kDa constitutive HSP
      (HSC70), the 72 kDa stress-inducible HSP (HSP70), and the 27 kDa small HSP
      (HSP27) was analyzed in white matter and myelin from central nervous system (CNS)
      tissue of MS and normal subjects using a combination of immunocytochemistry and
      quantitative immunoblotting. Plaques of all types were sharply defined by reduced
      immunostaining for HSC70, and shown by immunoblotting to contain 30 to 50% less
      HSC70 than surrounding white matter or normal tissue. In contrast, HSP27 was
      markedly enhanced 2.5- to 4-fold in plaque regions, especially in fibrous
      astrocytes and in hyperplastic interfascicular oligodendrocytes at the lesion
      edge. HSP70 was less abundant than HSC70, and no significant differences in HSP70
      levels were noted between MS and normal white matter. Myelin isolated from active
      plaques contained 3- to 4-fold more HSC70 than normal myelin. Pronounced
      expression of HSP70 and HSP27 was also found in MS myelin, although neither
      protein was detected in normal myelin. Thus, white matter undergoing immune
      mediated destruction in MS was associated with altered distribution and
      expression of HSC70 and HSP27. These changes may initially serve to protect
      myelin from further destruction and facilitate repair; however, enhanced
      expression of HSC70, HSP70, and HSP27 in myelin may subsequently present as
      additional immune targets involved in the progression of disease.

PMID- 9184658
TI  - Inhibition of tyrosine hydroxylase expression within the substantia nigra of mice
      infected with canine distemper virus.
AB  - Experimental infection of mouse brain with a neuroadapted strain of canine
      distemper virus (CDV) leads to early acute encephalitis, followed by late
      neurological diseases such as motor pathologies (paralysis and turning behavior)
      or obesity syndrome. We have previously shown that, during the early stage of
      infection, CDV replicates transiently in selective structures of the brain
      including the substantia nigra, a structure known to play a critical role in
      motor control. In this study we demonstrate that CDV replication in the
      substantia nigra induces an early decrease in transcript level of tyrosine
      hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. The CDV
      infection of neuroblastoma cell culture, constitutively expressing TH, results in
      downregulation of TH transcription in the absence of cell death. In the few
      surviving mice with motor deficiencies, a pronounced decrease in TH expression is
      associated with a loss of dopaminergic cell bodies in the absence of any viral
      transcripts and proteins, suggesting that the initial CDV infection was
      sufficient to trigger irreversible neurodegenerative processes.

PMID- 9184659
TI  - The neuropathology of HIV-infected African children in Abidjan, Cote d'Ivoire.
AB  - In an autopsy study of HIV-infected children in Abidjan, Cote d'Ivoire, the
      neuropathology of 76 HIV-1- and 2 HIV-2-positive children was compared with that
      of 77 frequency-matched HIV-negative children, in whom the systemic pathology was
      also known. Seventy of the 78 HIV-seropositive children were confirmed as HIV
      infected, as determined by combined serology, IgA Western blots and
      clinicopathological criteria. The HIV-negative children showed a high background
      level (n = 49, 64%) of neuropathological abnormalities, including nonspecific
      inflammatory infiltrates, micromineralization, and bacterial and lymphocytic
      meningitis. In the HIV-positive children, HIV encephalitis was found in 4 (6%),
      cytomegalovirus in 2 (3%), toxoplasmosis in 3 (4%) and measles encephalitis in
      one (1%). Bacterial meningitis was equally common in both groups, but cerebral
      malaria was less common (n = 2, 3%) in HIV-positive than in HIV-negative children
      (n = 11, 14%). The low prevalence of HIV encephalitis may reflect comparatively
      early death in HIV infection in Africa as compared with our experience in Europe
      and the US.

PMID- 9184660
TI  - Mice deficient in all forms of lysosomal beta-hexosaminidase show
      mucopolysaccharidosis-like pathology.
AB  - Lysosomal beta-hexosaminidase consists of 2 subunits, alpha and beta. Mutations
      in the alpha-subunit gene cause Tay-Sachs disease, while mutations in the beta
      subunit gene cause Sandhoff disease. Mice generated by targeted disruption of
      either the alpha- or beta-subunit genes displayed the pathological features of
      Tay-Sachs disease or Sandhoff disease, respectively. In this report we describe
      the pathologic features of mice that carry both disrupted genes and that are
      deficient in all forms of beta-hexosaminidase activity. These mice displayed
      physical dysmorphia and extensive neuro-visceral storage. Neurons in the CNS and
      PNS contained pleomorphic inclusions in addition to membranous cytoplasmic bodies
      characteristic of gangliosidosis. Diffuse hypomyelination was also apparent in
      the CNS. Vacuolated cytoplasm was a conspicuous feature of chondrocytes,
      osteocytes and renal tubular epithelium on routine hematoxylin and eosin (H&E) 
      stained sections. Numerous vacuolated cells were also noted in the connective
      tissue, cornea, heart valves, arterial walls, liver, spleen, skin and throughout
      other visceral organs. These vacuolated cells stained positive with PAS,
      colloidal iron and alcian blue, indicating an accumulation of glycosaminoglycans.
      Furthermore, cultured fibroblasts showed a defect in the degradation of
      glycosaminoglycans, and glycosaminoglycans were excreted in the urine of these
      mice (1). Thus, morphological and biochemical features in these mice are
      consistent with those of mucopolysaccharidosis and demonstrate an essential role
      of beta-hexosaminidase in the degradation of glycosaminoglycans.

PMID- 9184661
TI  - The interaction of growth rates and diffusion coefficients in a three-dimensional
      mathematical model of gliomas.
AB  - This paper is a natural three-dimensional extension of a simple two-dimensional
      mathematical model of glioma growth and diffusion. The model was originally
      constructed to simulate a case of recurrent anaplastic astrocytoma treated with
      chemotherapy, and then modified to allow estimation of the effects of the extent
      of surgical resection and of variations in growth and diffusion to cover the
      whole range of glioma behavior. Growth is considered to be constant and
      exponential (analogous to continuously compounding interest) and is expressed as
      a decimal fraction per day; the diffusion coefficient is expressed as cm2 per
      day. Model predictions suggest that diffusion, practically ignored until the
      present, is a more important component of glioma growth than the growth rate.
      Even with very early diagnosis, only those tumors with a low diffusion
      coefficient and a rapid growth rate benefit from a wide resection. Surgical
      resections generally fail, just as dropping fire-fighters into the burned out
      center of a forest fire fails, the action being on the periphery as the tumor
      cells or fires spread out from the center.

PMID- 9184662
TI  - Laterality in the histological effects of injections of amyloid-beta 25-35 into
      the amygdala of young Fischer rats.
AB  - We have observed that single amyloid-beta 25-35 (A beta) injections (5.0 nmol)
      into the right amygdala of rats produce progressive cytoskeletal and astrogliotic
      reactions not only within the amygdala, but also in distal brain regions that
      project to the amygdala. To determine if these effects are potentiated by
      bilateral injections, we injected A beta (5.0 nmol) into the left and right
      amygdala of young male Fischer rats. Animals were sacrificed 32 days
      postoperatively. Bilateral infusions of A beta induced significant neuronal
      shrinkage, tau-2 neuronal staining, and reactive astrocytosis within the right
      amygdala and/or hippocampus, compared with vehicle-treated rats. Surprisingly,
      the same brain regions within the left hemisphere were significantly less
      affected even though no differences were observed between the left and right
      amygdala in the size of Congored-positive A beta deposits. Unilateral injections
      of A beta into the left amygdala led to significant histological changes in the
      right amygdala and hippocampus, but not in the same brain regions within the left
      hemisphere. These results suggest a laterality in the histopathological effects
      of A beta in male Fischer rats. Identification of the cause for the lateralized
      effect of A beta may prove valuable for understanding the etiology of Alzheimer
      disease and provide possible therapeutic strategies designed to slow the
      progression of the disease.

PMID- 9184663
TI  - Cortical degeneration in progressive supranuclear palsy. A comparison with
      cortical-basal ganglionic degeneration.
AB  - We report 3 patients with progressive supranuclear palsy (PSP) who developed limb
      apraxia, focal dystonia, and arm levitation late in the course of the disease.
      Neuropathological examination revealed cortical degeneration in addition to the
      characteristic pathological findings of PSP. Semiquantitative comparative
      histological and immunohistological studies of the neocortex of these patients as
      well as 5 cases of classical PSP and 4 cases of cortical-basal ganglionic
      degeneration (CBGD) revealed a distinctive form of cortical degeneration in PSP.
      The cortical degeneration was often circumscribed and confined to premotor and
      motor cortex. It was characterized by neuronal loss and gliosis. Swollen neurons
      were only rarely observed in neocortex of PSP cases in contrast with CBGD, where
      they were abundant. Neuronal and glial tau as well as tau immunoreactive threads
      were seen in both PSP and CBGD, but were more abundant in CBGD. The appearance of
      tau reactive astrocytes also differed in both disorders; tufted astrocytes were
      seen exclusively in PSP, while typical annular astrocytic plaques were confined
      to CBGD. These observations indicate that cortical degeneration occurs in PSP and
      may be associated with atypical clinical manifestations that lead to diagnostic
      difficulties.

PMID- 9184664
TI  - Expression of NF2-encoded merlin and related ERM family proteins in the human
      central nervous system.
AB  - Germline mutations of the neurofibromatosis 2 (NF2) gene are associated with an
      increased incidence of gliomas and glial harmartomas, suggesting a role for the
      NF2-encoded protein, merlin, in glial growth control. Using monoclonal and
      polyclonal anti-merlin antibodies for Western blotting and immunohistochemistry,
      we evaluated the cellular pattern of merlin expression in the normal human
      central nervous system (CNS), reactive gliosis; and NF2-associated glial
      hamartomas. In the normal CNS, merlin is widely expressed in coarse cytoplasmic
      granules in both glia and neurons, with less pronounced expression in other
      cells. Merlin is also expressed in reactive astrocytes and in the astrocytes of
      NF2-associated glial hamartomas. In reactive astrocytes, however, merlin is also
      present at the cell membrane and in cellular processes, suggesting redistribution
      of the protein in activated cells. Merlin is structurally related to ezrin,
      radixin and moesin, which are also expressed in the CNS, as demonstrated by
      Western blotting. The pattern of merlin expression, however, is distinct from
      that of ezrin, which has been previously described, and that of moesin, in which
      immunohistochemistry with an anti-moesin antibody showed expression in
      endothelial cells, glia and neurons in a membranous or diffuse cytoplasmic
      pattern. These findings imply that merlin has widespread and specific functions
      in the human central nervous system.

PMID- 9184665
TI  - Detection of malignant cells in cerebrospinal fluid using fluorescence in situ
      hybridization.
AB  - Cytologic examination of cerebrospinal fluid (CSF) is the diagnostic gold
      standard for leptomeningeal metastasis (LMM). However, this technique is only
      moderately sensitive when routine staining procedures are applied. The use of
      fluorescence in situ hybridization (FISH) to identify malignant cells may have an
      additional value in diagnosing LMM, since numerical chromosomal aberrations (NCA)
      can be detected at the single cell level. We tested the feasibility of FISH to
      detect tumor cells in CSF by analyzing 22 samples with proven LMM with a probe
      for chromosome 1 (1q12) to detect NCA in the cells. A control group consisted of
      samples from 10 patients with inflammatory neurologic disease. In 7 LMM samples
      no cells or only lysed cells were found, due to time delay before fixation. Of
      the other 15 LMM samples analyzed, 13 showed NCA (87%), while no NCA were found
      in the control group. Our results indicate that FISH may be a useful additional
      diagnostic tool to the cytodiagnosis of CSF in cases of LMM. We expect that FISH
      can become an additional marker for malignancy at the single cell level in
      patients with LMM, which may also be of use to determine the effect of therapy
      for LMM.

PMID- 9184666
TI  - Cholesterol and bile acid metabolism after selective portal vein ligation.
AB  - AIM: To examine the regulatory effect of bile acid level on bile acid synthesis
      in the liver. METHODS: The portal branch perfusing left lateral and median lobes
      of the liver was ligated in rats and the activities of hepatic microsomal
      cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile acid synthesis,
      3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and intrahepatic
      concentrations of cholesterol and bile acids were determined in the liver lobes
      deprived of and supplied with portal blood on Days 0, 1, 2, 4, and 7 after
      selective portal vein ligation (SPVL). RESULTS: In the portal vein (PV)-ligated
      lobes, liver weight decreased, hepatic cholesterol concentration was unchanged,
      and microsomal cholesterol concentration increased after SPVL. In the PV
      nonligated lobes, liver weight increased, hepatic cholesterol concentration
      increased, and microsomal cholesterol concentration was unchanged. There were no
      significant differences in the activities of HMG-CoA reductase and cholesterol 7
      alpha-hydroxylase among the PV-ligated and PV-nonligated lobes and the sham
      operated controls. Intrahepatic bile acid level increased significantly in the PV
      nonligated lobes for 4 days after SPVL, whereas those were essentially constant
      in the PV-ligated and the sham-operated control liver. Despite significant
      changes in the concentrations of intrahepatic cholesterol and bile acid, no
      significant correlations were observed between these concentrations and the
      activities of cholesterol 7 alpha-hydroxylase. CONCLUSIONS: SPVL causes atrophy
      and hypertrophy of the PV-ligated and nonligated liver lobes, respectively,
      without any significant changes in cholesterol and bile acid synthesis.
      Intrahepatic concentrations of bile acids and cholesterol have no regulatory
      effect on cholesterol 7 alpha-hydroxylase activity in the SPVL rat model.

PMID- 9184667
TI  - Role of complement in rats injected with liposome-encapsulated hemoglobin.
AB  - Previous studies have documented that liposome-encapsulated hemoglobin (LEH) can
      cause a rapid and transient thrombocytopenia following intravenous injection into
      small animals. The present study evaluated the role of complement during the LEH
      induced thrombocytopenia in rats. We have compared changes in platelet levels in
      the blood, platelet organ distribution, and total hemolytic complement levels
      following intravenous administration of LEH in control and complement-depleted
      rats. Changes in platelet organ distribution at various times after LEH
      administration were monitored by labeling autologous platelets with indium-111
      (111In)-oxine and imaging the 111In-platelets with a gamma camera after
      reinjection. Platelet counts were determined by light-scattering methods and by
      following 111In radioactivity at various times after LEH administration. Platelet
      levels did not significantly change for the complement-depleted rats during the
      60 min following an injection of LEH, whereas thrombocytopenia (40% decrease) was
      noted within 4 min post-LEH-injection for control rats with a gradual return to
      baseline circulating platelet levels within 60 min. This drop in circulating
      platelets was correlated with a rapid redistribution of 111In-platelets from the
      circulation to the lungs and liver, whereas complement-depleted rats showed no
      transient movement of the 111In-platelets from the circulation. Baseline
      complement levels of 21.6 +/- 2.2 CH50/ml for control rats and 0.2 +/- 0.1
      CH50/ml for complement-depleted rats did not significantly change during the 60
      min following LEH administration. This study suggests that complement must be
      present during LEH-induced transient thrombocytopenia, as complement-depleted
      rats underwent no thrombocytopenia, and that the transient LEH-induced
      thrombocytopenia may be associated with complement activation.

PMID- 9184668
TI  - Functional and morphological evaluation of canine veins following preservation in
      different storage media.
AB  - Injuries of endothelial and smooth muscle cells of autologous vein due to
      preservation in standard storage media may be responsible for graft failure. The
      effects of vein preservation with University of Wisconsin solution (UWs) on
      endothelial and smooth muscle cell function and morphology were compared to the
      effects of preservation with autologous whole blood (AWB) and normal saline (NS),
      which are frequently used in cardiovascular surgery. Canine external jugular and
      common femoral vein segments were preserved in the different solutions at 4
      degrees C for 45 min and 24 hr. Rings (4-5 mm in length) from control and
      preserved veins were evaluated by isometric tension studies at 37 degrees C and
      by scanning and transmission electron microscopy. Differences between groups were
      evaluated by Student's t test or Mann-Whitney U test and by analysis of the
      variance, and considered to be significant at P < 0.05. Sensitivities to
      norepinephrine (NE) showed that a 45-min vein storage in AWB (5.7 +/- 0.2
      mumol/L) but not in NS (5.8 +/- 0.2 mumol/L) or UWs (6.5 +/- 0.2 mumol/L) had a
      deleterious effect on function of smooth muscle (P < 0.05) when compared to
      control veins (6.6 +/- 0.2 mumol/L). Maximum contractile responses and
      sensitivities to NE were significantly altered (P < 0.05) after 24-hr vein
      storage in AWB (0.09 +/- 0.02 g/mm2 and 5.4 +/- 0.07 mumol/L) and NS (0.12 +/-
      0.03 g/mm2 and 5.6 +/- 0.08 mumol/L) but not in UWs (0.36 +/- 0.06 g/mm2 and 6.4
      +/- 0.07 mumol/L). With both storage times, acetylcholine-induced endothelium
      dependent maximum relaxations and sensitivities were significantly reduced (P <
      0.05) in veins stored in AWB and NS, but not in UWs, compared with controls.
      Similarly, transmission electron microscopy revealed marked neutrophil migration
      beneath the intimal surface of vessels and extensive separation and desquamation
      of endothelial cells with exposure of subendothelial structures in veins stored
      in AWB and NS. The results suggest that UWs is a suitable storage medium when
      compared to AWB and NS.

PMID- 9184669
TI  - Evaluation of normothermic ischemia and simple cold preservation injury in pig
      kidney by proton nuclear magnetic resonance spectroscopy.
AB  - The isolated perfused pig kidney (IPK) model was used to mimic the non-heart
      beating donor situation. This model was performed to assess initial renal
      functions after normothermic ischemia, cold flush, and 24 hr cold-storage
      preservation (CSP) with Euro-Collins and to determine normothermic ischemia and
      reperfusion impairment by biochemical, histological, and proton nuclear magnetic
      resonance (NMR) spectroscopy analysis. Twenty-four pig kidneys were used. There
      were three experimental groups: Group 1 (G1), control kidneys flushed with cold
      heparinized saline and immediately perfused; Group 2 (G2), cold flush followed by
      24 hr CSP and reperfusion; and Group 3 (G3), 30 min of normothermic ischemia
      followed by cold flush and 24 hr CSP and reperfusion. Kidneys were perfused for 2
      hr at 37.5 degrees C for functional evaluation. Perfusate flow rate is
      significantly different for G3 (P < 0.01). Glomerular filtration rate is less in
      G3 (P < 0.05). Fractional reabsorptions of sodium (FRNa+) and glucose (Glc)
      excretion in urine are different in G3 (P < 0.01 and P < 0.05, respectively).
      Amino acid excretion in NMR spectroscopy was higher in G3 (P < 0.05). Elevated
      levels of trimethylamine-N-oxide (TMAO) and lactate (Lac) were detected by proton
      NMR spectroscopy in G2 and particularly G3. A peak is present in G3 and related
      with poor glomerular and tubular functions and worse histological data.
      Malondialdehyde tissue level was higher in G3. This study shows that the IPK with
      proton NMR spectroscopy may be a useful method in the evaluation of kidneys after
      cold ischemia and transplantation. This model might be suitable for a variety of
      experimental protocols, particularly to improve functional performance after
      ischemia and reperfusion.

PMID- 9184670
TI  - Effects of physical barriers in prevention of adhesions: an incisional hernia
      model in rats.
AB  - BACKGROUND: Adhesion formation between viscera and mesh is almost inevitable
      following incisional hernia repair with prosthetic mesh. Such adhesions may lead
      to intestinal obstruction and enterocutaneous fistulae formation and make further
      laparotomies extremely difficult. Sodium carboxymethylcellulose (SCMC) and
      Interceed TC7 (oxidized regenerated cellulose) as physical barriers have been
      shown to be effective in reducing postoperative adhesions. MATERIALS AND METHODS:
      To evaluate the effects of SCMC and Interceed TC7, we used an incisional hernia
      model in rats. A ventral abdominal defect (15 x 25 mm) was created in each of 36
      male rats which were then divided into three equal groups. In Group I (control)
      the defect was repaired with polypropylene mesh (PPM) only; in Group II the
      defect was repaired after a layer of Interceed TC7 was laid over the viscera with
      Interceed TC7-covered PPM; in Group III the defect was repaired after a layer of
      SCMC was laid over the viscera with SCMC-coated PPM. Six of the animals from each
      group were sacrificed at Postoperative Day 7 and the adhesions were scored. The
      remaining 6 were sacrificed at Day 30 and histological evaluation was made in
      addition to the adhesion score. RESULTS: Animals in the SCMC-treated group
      developed significantly less adhesions (P = 0.0002) compared with control and
      Interceed TC7-treated groups. However, histological analysis revealed poor
      fibroblast proliferation with impaired wound healing in the SCMC group.
      CONCLUSION: SCMC prevented adhesion formation but seriously impaired wound
      healing, and Interceed TC7 was ineffective in preventing adhesion in this model.

PMID- 9184671
TI  - Altered ionic calcium and cell motion in ventricular myocytes after cutaneous
      thermal injury.
AB  - Cutaneous thermal injury resulting in burns covering approximately 45% of the
      total body surface area initiates metabolic alterations which contribute to
      subsequent myocardial dysfunction. Alterations in calcium homeostasis have been
      proposed as one mechanism by which burn injury alters organ function. This study
      used fura-2 and time-resolved single cell fluorescence microscopy to examine
      stress-related alterations in intracellular calcium in isolated adult rat cardiac
      myocytes. Ventricular myocytes were isolated from rats given a full-thickness
      scald burn comprising 43% of the total body surface area and fluid resuscitated
      with lactated Ringer's by the Parkland formula; control animals were included for
      comparison. Burn trauma caused a significant increase in cardiac myocyte maximal
      (peak systolic) and minimal (diastolic) mean cytosolic free calcium concentration
      ([Ca2+]i) transient ratios when compared to [Ca2+]i transient ratios measured in
      control rats. Isoproterenol application altered the time course of the [Ca2+]i
      transients of normal myocytes but this response was not observed in myocytes from
      the thermally injured rats. In addition, isoproterenol application to normal
      myocytes produced a significant increase in the amplitude of cell edge motion
      (+50%) compared to the cell edge motion measured in myocytes without
      isoproterenol stimulation; however, this cell motion response did not occur after
      isoproterenol application to myocytes from thermally injured rats. Caffeine
      application increased the maximal and minimal [Ca2+]i transient ratios of all
      myocytes, regardless of a burn injury, and the time course of the [Ca2+]i
      transients from the two groups appeared similar in the presence of caffeine as
      the myocytes progressed to contracture. Our data suggest that burn-mediated
      alterations in calcium homeostasis contribute, in part, to the cardiac
      contractile dysfunction which occurs after burn injury.

PMID- 9184672
TI  - Endothelial cells exhibit differential chemokinetic and mitogenic responsiveness
      to alpha-thrombin.
AB  - Rapid regeneration of the endothelium is a critical component of vascular wall
      repair because limitations of this process enhance early thrombotic and
      vasospastic complications, as well as late sequelae of recurrent lesion
      formation. We have postulated that direct activation of the thrombin receptor
      initiates both mitogenic and chemokinetic endothelial behavior which facilitates
      intimal repair. To characterize the role of the thrombin receptor in human
      endothelial cell (EC) proliferation and migration, we investigated the effects of
      both alpha-thrombin (0.5-10 U/ml) and its receptor-activating peptide (TRAP; 1
      100 microM). Responses of human aortic (HAEC) and umbilical vein (HUVEC) were
      characterized using [3H]thymidine and 61Cr microcarrier bead assays of
      proliferation and migration, respectively. Expression of motility-related genes
      was evaluated using a ribonuclease protection assay. Thrombin exerts both of its
      chemokinetic and mitogenic effects differentially in human endothelial cells.
      Following 2 or 4 days in culture, HUVEC proliferation increased two- to threefold
      after exposure to thrombin, primarily in the low concentration range (P < 0.05).
      However, HACE proliferation was inhibited up to 50% after a 4-day incubation
      period (P < 0.005). These mitogenic effects, including the inhibition of aortic
      endothelial cell proliferation, were reproduced, in part, by thrombin receptor
      activation with TRAP. In contrast, thrombin stimulates migratory responses in
      HAEC, but not HUVEC. However, this behavior was not reproduced by TRAP. It is
      noteworthy that urokinase-plasminogen activator (u-PA) expression was much more
      strongly expressed in migrating HAEC than in the HUVEC population. Moreover, when
      stimulated with thrombin, u-PA gene expression was significantly augmented in
      HAEC. It has been speculated that an effective human thrombin receptor (HTR)
      antagonist may reduce the proliferation of vascular smooth muscle cells and the
      development of a restenotic lesion following arterial wall injury. Our data
      suggest that such an inhibitor will likely also accelerate intimal regeneration
      through a dominant effect on limiting the HTR inhibitory effect on endothelial
      proliferation.

PMID- 9184673
TI  - Graft persistence effectively induces and maintains donor-specific
      unresponsiveness.
AB  - BACKGROUND: In the present study we attempted to evaluate the role of the graft
      as an alloantigen in induction and maintenance of donor-specific prolongation of
      allograft survival by short course(s) of FK506 treatment in rat heart
      transplantation. Materials and methods. In the WKA/Qdj-to-LEW combination group,
      FK506 (3 mg/kg/day, 7 days, s.c.) was administered from Day 0 after cardiac
      transplantation. A second WKA/ Qdj cardiac graft was transplanted on Day 14 into
      the LEW recipient after removal of the first graft on Day 3 or Day 7. In other
      groups an additional course of FK506 (3 mg/kg/day, 7 days, s.c.) was given from
      Day 35. A second WKA/Qdj cardiac graft was transplanted on Day 49 into the LEW
      recipient after removal of the first graft on Day 7 or Day 28. RESULTS: A short
      course of FK506 treatment allowed for survival prolongation of a cardiac
      allograft [mean survival time (MST) = 42.8 days]. Removal of the first graft on
      Day 7 (MST = 16.4 days) but not on Day 3 (MST = 10.2 days) caused donor-specific
      prolongation of the second allograft survival, which was significantly shorter
      than that in the recipient without the graftectomy (MST = 32.8 days). When
      graftectomy was performed on Day 3, there were immunohistochemically detectable
      levels of donor class II expressing cells in the recipient spleen on Day 7,
      indicating that the presence of the graft more effectively induced
      unresponsiveness than microchimerism alone. The additional course of FK506
      treatment on Day 35 maintained graft survival (MST > 90.6 days). Removal of the
      first graft on Day 7 (MST = 13.5 days) or Day 28 (MST = 24.7 days) did not show
      significant prolongation of the second allograft survival, whereas significant
      survival prolongation of the second graft was observed in the recipient without
      the graftectomy (MST = 38.8 days). However, marked survival prolongation of the
      second donor-specific allograft in half of the recipients that had received the
      second course of FK506 treatment after graftectomy on Day 28 indicates that
      residual donor antigen can function as tolerizing antigen with an FK506
      supplement. CONCLUSIONS: We concluded that the persistence of a graft more
      effectively induces and maintains donor-specific unresponsiveness than does the
      chimeric state of graft-derived cells alone under immunosuppression by FK506 in
      the rat heart transplantation model.

PMID- 9184674
TI  - Retroperitoneal and intraperitoneal CO2 insufflation have markedly different
      cardiovascular effects.
AB  - Both retroperitoneoscopic and laparoscopic surgical approaches to kidney and
      adrenal gland have been reported but their cardiopulmonary pathophysiology has
      been incompletely characterized. To test the hypothesis that these approaches
      have markedly different impact on the circulatory and respiratory systems, we
      assessed at similar insufflation pressures alterations in cardiovascular and
      respiratory variables during retroperitoneal and intraperitoneal CO2
      insufflation. Eighteen healthy, anesthetized (propofol, alfentanil, vecuronium),
      mechanically ventilated pigs were randomly instrumented for either
      retroperitoneoscopic (n = 9) or laparoscopic (n = 9) surgery. After CO2
      insufflation cardiovascular and respiratory variables were measured at four
      cavity pressures (baseline, 10, 15, and 20 mmHg), while end-expiratory CO2
      tension was maintained by adjusting tidal volume. Data were analyzed for both
      insufflation-pressure-dependent and group effects by one-way and two-way ANOVA
      for repeated measurements, respectively, followed by Newman-Keuls post hoc test
      (P < 0.05). Cardiac output, mean arterial, pulmonary artery, central venous, and
      femoral venous pressures increased significantly in both groups in an
      insufflation-pressure-dependent fashion. However, changes in cardiac output (P <
      0.001), pulmonary artery (P < 0.007), central venous (P < 0.001), and iliac
      venous pressures (P < 0.001) for the same insufflation pressure were markedly and
      significantly greater with intraperitoneal than retroperitoneal CO2 insufflation.
      Most important, intraperitoneal unlike retroperitoneal insufflation induced a
      marked inferior vena caval pressure gradient (8.9 +/- 1.1 mmHg vs 1.0 +/- 0.5
      mmHg, P < 0.00001). While both retroperitoneal and intraperitoneal CO2
      insufflation required increased tidal volumes to adjust endtidal CO2 tension to
      baseline, intraperitoneal CO2 insufflation resulted in a significantly greater
      increase of mixed venous and arterial carbon dioxide tensions (P < 0.007) even at
      similar insufflation pressures. Furthermore, significantly greater peak airway
      pressures (P = 0.018) were required with intraperitoneal than with
      retroperitoneal insufflation to administer the same tidal volume, indicating a
      greater decrease in quasi-static compliance with intraperitoneal insufflation (P
      = 0.0436). Thus, (i) cardiovascular and respiratory changes are much less during
      retroperitoneal than intraperitoneal CO2 insufflation, even at the same
      insufflation pressures, and (ii) retroperitoneal CO2 insufflation unlike
      intraabdominal CO2 insufflation does not induce an inferior vena caval pressure
      gradient and hence does not appear to impair systemic lower body venous return up
      to insufflation pressures of 20 mmHg.

PMID- 9184675
TI  - Effects of cytokine antagonists on the hepatic acute-phase response.
AB  - Endotoxin-induced hepatic acute-phase protein synthesis has been thought to be
      primarily regulated through cytokines such as interleukin-1 (IL-1) and
      interleukin-6 (IL-6). Previously, it was found that a 23-kDa murine acute-phase
      protein, the lipopolysaccharide (LPS)-induced protein (LIP), was synthesized
      following treatment of hepatocytes in vitro with LPS. Since this protein was also
      induced by IL-1 and IL-6, the present studies were undertaken to determine if the
      effect of endotoxin was mediated through these cytokines. Primary cultures of
      murine hepatocytes were treated with LPS, IL-1, IL-6, or an LPS-stimulated
      macrophage supernatant in the presence or absence of the IL-1 receptor antagonist
      (IL-1 RA) and/or an anti-IL-6 antibody. The cells were then radiolabeled with
      [35S]methionine. LIP was detected by electrophoresis and autoradiography of the
      secreted proteins. In vitro, IL-1 RA completely inhibited the stimulation of LIP
      synthesis elicited by IL-1 and the macrophage supernatant, but did not affect LPS
      stimulated synthesis of this protein. The anti-IL-6 antibody inhibited IL-6
      triggered synthesis of LIP, but had no effect on LPS-stimulated synthesis.
      Hepatocytes isolated from mice treated in vivo with both IL-1 RA and LPS
      synthesized LIP to the same degree as hepatocytes isolated from mice treated with
      LPS alone. LPS-stimulated synthesis of LIP in vitro does not require IL-1 or IL-6
      as an obligatory intermediate. These results are consistent with the hypothesis
      that endotoxin can directly stimulate hepatocyte acute-phase protein synthesis in
      the absence of cytokines.

PMID- 9184676
TI  - The role of platelet-activating factor in conscious, normotensive endotoxemia.
AB  - The effects of endotoxin have been postulated to be mediated in large part by
      release of endogenous platelet-activating factor (PAF) due to the similarity of
      their hemodynamic and gastric effects in anesthetized animals, and to the ability
      of PAF inhibitors to ameliorate endotoxin's effects. We chose to examine the
      relationship with doses that would not produce circulatory shock, in unrestrained
      conscious animals, in order to mimic clinical situations. Adult male rats were
      prepared with vascular access, hemodynamic and temperature monitors, and gastric
      strain gauge transducers. After an overnight fast, rats received a 4-hr infusion
      of saline (0.5 ml/hr), endotoxin (12.5 mg/kg/hr), PAF (36 micrograms/kg/hr, or
      600 ng/kg/min), or endotoxin plus the PAF inhibitor CV 3988 (1 mg/kg/hr, after an
      initial pretreatment of 1 mg/kg). Rats were killed, stomachs were harvested, and
      contents were analyzed at the end of the infusions. Blood pressure was not
      affected by any treatment, but all treated groups developed diarrhea and
      vasodilatation. Endotoxin and PAF infusions decreased heart rate and body
      temperature to a similar extent, although the PAF effect on temperature was
      delayed. The PAF inhibitor did not prevent the body temperature effect, but did
      reverse it. Gastric secretions were affected by PAF to a lesser extent than by
      endotoxin, and the PAF inhibitor did not decrease endotoxin's gastric secretory
      effects. PAF has similar systemic and gastric effects to endotoxin in conscious,
      unrestrained, normotensive animals. The systemic effects of endotoxin at 12.5
      mg/kg/hr were prevented or reversed by the PAF inhibitor CV-3988 at 1 mg/kg/hr,
      but not the gastric secretory effects.

PMID- 9184677
TI  - Xanthine oxidase inhibition prevents mesenteric blood flow deficits after
      resuscitated hemorrhagic shock by preserving endothelial function.
AB  - To determine the contribution of xanthine oxidase-mediated endothelial
      dysfunction to the blood flow deficits seen in the mesenteric circulation after
      resuscitated hemorrhagic shock, rats were prepared for intravital microscopic
      study then bled to 50% of baseline blood pressure for 60 min. Treatment animals
      received a 50 mg/kg bolus and a 25 mg/kg/hr infusion of the xanthine oxidase
      inhibitor allopurinol (allo) after shock but before resuscitation with shed blood
      and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res)
      and a nonhemorrhage group served as controls. Endothelial function was quantified
      at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a change in
      mesenteric vessel diameter after topical application of acetylcholine (Ach), an
      endothelial-dependent vasodilator. Resuscitation restored cardiac output and
      blood pressure in both groups. First-order arteriolar blood flow (A1) remained
      depressed in the Std Res group but was restored to baseline in the group treated
      with allo. A1 arterioles demonstrated a 22 and a 27% reduction in ability to
      dilate to Ach at R30 and R90 after Std Res. V1 venules demonstrated a 39 and a
      36% reduction in ability to dilate to Ach at R30 and R90 after Std Res.
      Endothelial-dependent vasodilation and blood flow were preserved in the group
      receiving Std Res plus allo. The preservation of endothelial function correlated
      with the restoration of microvascular blood flow postresuscitation. These data
      suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to
      endothelial dysfunction and blood flow deficits in the mesenteric
      microcirculation after resuscitated hemorrhagic shock, the effect of which can be
      attenuated by the addition of the xanthine oxidase inhibitor allopurinol to
      standard resuscitation.

PMID- 9184678
TI  - Hemodialysis access graft stenosis: percutaneous transluminal angioplasty.
AB  - Maintenance of dialysis access continues to plague care of the patient with ESRD.
      Because of the poor outcomes from surgical revision, there is increasing interest
      in balloon angioplasty as a technique for dilating stenoses in the functioning,
      but compromised graft. Forty patients treated with percutaneous transluminal
      angioplasty (PTA), without subsequent intervention, for graft dysfunction were
      retrospectively studied. Time to thrombosis of the graft was noted. Patency was
      determined using the Kaplan-Meier technique. Patency following PTA at 1, 6, and
      12 months was 76, 27, and 10%. Patency following PTA of arteriovenous graft
      stenoses results in disappointing medium and long-term patency. Alternate
      strategies for improving patency of these conduits should be explored.

PMID- 9184679
TI  - Re: Nashville experience with liver transplantation in U.S. Veterans.

PMID- 9184680
TI  - Cancer incidence and mortality: the priority of screening frequency and
      population coverage.
AB  - In addition to the usual measures of screening-test performance, it is important
      to consider testing frequency when evaluating a screening program. Data on which
      to base recommendations for the timing of screening tests are urgently needed.
      For example, in the cases of cervical and colon cancer, when the target is a
      precursor lesion, research indicates that less frequent screening may be
      appropriate. This finding may not apply, however, to screening for breast cancer
      by mammography, which requires currently recommended intervals for the early
      detection of malignancies. Resources now allocated to breast cancer might more
      effectively be applied to the construction of tests that would permit longer
      intervals between screenings. To achieve the National Cancer Institute's goal of
      reducing cancer mortality in the United States by the year 2000, it will be
      important to review the balance between population coverage and individual
      screening for each cancer and to emphasize prevention strategies that maximize
      population coverage while minimizing expenditures.

PMID- 9184681
TI  - The politics of "Drive-through deliveries": putting early postpartum discharge on
      the legislative agenda.
AB  - Since May 25, 1995, twenty-nine states have adopted "early discharge" legislation
      or comparable regulations, mandating insurers to cover minimum postpartum
      hospital stays. The topic of early discharge moved onto the agenda with notable
      speed, despite a lack of empirical evidence to support either those insurers who
      reduced the postpartum length of stay for mothers and babies or the new statutes
      that protected their right to longer stays. The new laws' simplicity and low cost
      as unfunded mandates accounted for much of their appeal, as did the symbolic
      power of the issue to doctors and patients, frustrated by managed care. Emotional
      constituent anecdotes, unsupported by definitive research findings, also
      influenced legislators.

PMID- 9184682
TI  - Impact of the Medicare Catastrophic Coverage Act on nursing homes.
AB  - The Medicare Catastrophic Coverage Act (MCCA) of 1988 altered eligibility and
      coverage for skilled nursing facility (SNF) care and changed Medicaid eligibility
      rules for nursing-home residents. Detailed data on the residents of a for-profit
      nursing-home chain and Medicare claims for a 1 percent sample of beneficiaries
      were used to examine the impact of the MCCA on nursing homes. The case mix of
      nursing-home admissions was scrutinized, specifically for length of stay,
      discharge disposition, rate of hospitalization, and changes in payer source.
      Findings revealed that, although the proportion of Medicare-financed nursing-home
      care increased, as did the case-mix severity of residents during the MCCA period,
      there was no corollary reduction in hospital use by nursing-home residents.

PMID- 9184683
TI  - Ambulatory mental health treatment under universal coverage: policy insights from
      Israel.
AB  - Untested assumptions concerning ambulatory treatment have shaped mental health
      policies for decades. Three opinions prevail: (1) all use is alike; (2) any use
      leads to high use; and (3) all high use is discretionary and therefore excessive.
      These assumptions were tested, using data from a nationwide survey of ambulatory
      utilizers in Israel, a country that has universal coverage. The findings, based
      on detailed clinical and treatment records, challenge all three assumptions.
      Moreover, they document a diversity of clinical needs while also verifying
      substantial variations in the type, frequency, and duration of treatment provided
      to meet those needs. In brief, Israeli data do not confirm continuing concerns by
      policy makers about uncontrollable use of services with expanded mental health
      coverage. Special policy limitations on mental health treatment should be
      reconsidered in light of empirical evidence from a system without the
      restrictions that exist in the United States.

PMID- 9184684
TI  - Developing tomorrow's integrated community health systems: a leadership challenge
      for public health and primary care.
AB  - As the nation's health system moves away from earlier models to one grounded in
      population health and market-based systems of care, new challenges arise for
      public health professionals, primary care practitioners, health plan and
      institutional managers, and community leaders. Among the challenges are the need
      to develop creative concepts of organization and accountability and to assure
      that dynamic, system-oriented structures support the new kind of leadership that
      is required. Developing tomorrow's integrated community health systems will
      challenge the leadership skills and integrative abilities of public health
      professionals, primary care practitioners, and managers. These leaders and their
      new organizations must, in turn, assume increased accountability for improving
      community health.

PMID- 9184685
TI  - In the soul.

PMID- 9184686
TI  - Advances in the treatment of vestibular disorders.
AB  - This article discusses the pathophysiology, evidence of treatment efficacy, and
      factors that contribute to improved treatment outcome in three different
      vestibular disorders. In patients with unilateral and bilateral vestibular loss,
      recent research suggests that customized, supervised exercises facilitate
      recovery of postural stability. These exercises are based on knowledge of normal
      vestibular function as well as on our understanding of the various compensatory
      mechanisms that can contribute to recovery. Recognizing the limitations of these
      compensatory mechanisms as substitutes for lost vestibular function is important
      in establishing treatment goals. Treatment of patients with benign paroxysmal
      positional vertigo (BPPV) is based on the identification of the specific canal
      involved and the anatomy of the labyrinth. Although patients with BPPV primarily
      experience brief episodes of vertigo, this disorder is also associated with
      postural instability, which may not resolve with remission of the positional
      vertigo.

PMID- 9184687
TI  - The role of vision and spatial orientation in the maintenance of posture.
AB  - This article reviews and analyzes the role of vision and spatial orientation in
      maintaining posture and balance. The key issues that relate to the development of
      postural control across the life span are discussed. Use of vision as a critical
      source of information that specifies spatial orientation in the environment is
      considered. We argue that the visual system functions as part of the perception
      action cycle as promoted in ecological psychology by James Gibson. We compare and
      contrast theory and evidence of both standard and ecological accounts of how the
      visual system perceives the information and the findings relative to the role of
      the retinal vision in processing and acting on information related to motion.
      Changes in the ambient optical array (optical flow) as a non-force field are
      compared with gravity-based perturbations relative to the possible influence of
      the non-force field to changes in the motor system. Finally, a summary of some of
      our own work is presented, with comments about implications for further research
      and possible applications to clinical practice.

PMID- 9184688
TI  - Evaluation of postural stability in children: current theories and assessment
      tools.
AB  - Children with many types of motor dysfunction have problems maintaining postural
      stability. Because maintenance of postural stability is an integral part of all
      movements, therapists evaluate and treat to improve postural stability in these
      children. This article reviews current pediatric assessment tools for postural
      stability and issues affecting testing this construct in children. The tests and
      measurements are classified according to their testing purpose and the National
      Center for Medical Rehabilitation Research disablement framework, focusing on the
      impairment and functional limitation dimensions. Postural stability is defined
      from a systems perspective with tests related to the sensory, motor, and
      biomechanical systems described. Reliability and validity information on the
      measurements is discussed. Relatively few measurements of postural stability in
      children are available that have acceptable reliability and validity
      documentation. Suggestions for research on test development in this area are
      discussed.

PMID- 9184689
TI  - Balance control during walking in the older adult: research and its implications.
AB  - In this article, we highlight the unique nature of balance control during walking
      in humans. A control framework, including proactive and reactive balance control,
      is introduced to lay out age-related changes in different balance control
      mechanisms during walking. Clinical implications that may be useful for
      clinicians for assessment and treatment of balance problems that occur during
      walking are also discussed.

PMID- 9184690
TI  - Use of neuromuscular electrical stimulation and [corrected] dorsal wrist splint
      to improve the hand function of a child with spastic hemiparesis.
AB  - This case report describes a program for a child with spastic hemiparesis who had
      previously received physical therapy with neuromuscular electrical stimulation
      (NMES). After a year without physical therapy, he returned to continue to receive
      NMES to strengthen muscles, increase sensory awareness, and improve hand
      function. The child quickly regained his previous level of functioning and made
      additional progress. After 38 sessions, he still lacked adequate wrist stability
      for independent hand function. A dorsal wrist splint was used to stabilize the
      wrist while NMES facilitated muscle activity of the hand and wrist. While wearing
      the splint, the child could use his hand independently without adult interference
      or "assistance," thus allowing motor learning to occur. After 24 additional
      sessions (i.e., 9 months of using the splint), the child could use the hand for
      activities such as tying his shoelaces without the splint. No increase in
      spasticity was seen in spite of strengthening the spastic finger flexors.

PMID- 9184691
TI  - Mechanisms of ataxia.
AB  - Ataxia, or incoordination of movement, is a disorder that can be caused by damage
      to several different nervous system structures. Common causes of ataxia include
      damage of the cerebellum and damage of sensory structures. Sensory ataxia is
      distinguishable from cerebellar ataxia, because the sensory ataxia causes
      symptoms to worsen when movements are made with the eyes closed. The basic
      mechanism underlying ataxia is not yet understood, although studies indicate that
      ataxia may be due in part to an inability to coordinate the relative activity of
      multiple muscles and adjust movements at a given joint for the effects of other
      moving joints (interaction torques). Based on these findings, it could be
      reasoned that treatments focusing on strategies to reduce the complexity of a
      movement by minimizing the number of moving joints or by stabilizing against the
      inertial effects of limb movement will improve function. 2,12-14,21-23 Further
      testing of treatments for ataxia, however, is needed. Ataxia may be best treated
      by teaching people to avoid rapid multijoint movements and instead make slower
      movements limited to single joints.

PMID- 9184692
TI  - Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen
      intermediates in vitro.
AB  - Apoptosis is a major mechanism of T cell elimination during ontogeny and
      tolerance induction as well as in autoimmunity. To assess the possible
      involvement of reactive oxygen and nitrogen intermediates (ROI and NO.) in T-cell
      apoptosis during autoimmune demyelination we investigated the effects of H2O2 and
      NO. in vitro on activated autoreactive CD4+ T cell lines capable of transferring
      experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune
      neuritis (EAN). For detection and quantitation of apoptotic cells, DNA
      fragmentation was assessed by in situ tailing with fluorescein-ddUTP and
      subsequent flow cytometric analysis. H2O2 applied directly to the cell cultures
      for 6 to 18 hr at concentrations of 10 to 300 microM and ROI released by
      combination of hypoxanthine and xanthine oxidase (HX/XO) caused apoptosis in a
      dose-dependent manner in 13-33% of T cells of neuritogenic and encephalitogenic T
      cell lines. Apoptosis induction could be suppressed by the H2O2-neutralizing
      enzyme catalase. NO. released by the penicillamine derivative SNAP induced
      apoptosis to a similar extent as ROI. Maximum values were 38% in an
      encephalitogenic V beta 8.2-T cell receptor-bearing T cell line and 26% in a
      neuritogenic T cell line. T cell lines with specificity to ovalbumin revealed
      slightly lower susceptibility to apoptosis induction by all three kinds of
      trigger, which is, however, most probably not due to the different antigen
      specificity, but rather a result of fewer in vitro restimulation cycles of these
      cells. In neuritogenic cells high-dose (100 units/ml) exogenous interleukin-2 (IL
      2) prevents H2O2-induced apoptosis. In conclusion, macrophage-derived reactive
      oxygen and nitrogen intermediates have the potency to limit inflammatory
      demyelination by elimination of autoreactive and bystander T cells via apoptotic
      cell death, and IL-2 is a rescue factor.

PMID- 9184693
TI  - Beta 2-integrin-mediated signal up-regulates counterreceptor ICAM-1 expression on
      human monocytic cell line THP-1 through tyrosine phosphorylation.
AB  - Intracellular cross-talk between LFA-1 and its counter receptor, intercellular
      adhesion molecule-1 (ICAM-1), on human monocytic cell line THP-1 was analyzed.
      Stimulation with mAb YH384 specific for LFA-1 alpha (CD11a) up-regulated ICAM-1
      expression on THP-1 cells. Cell surface expression of ICAM-1 on THP-1 cells was
      dose-dependently up-regulated and reached the maximal level 24 hr after
      stimulation with mAb YH384. Up-regulation of ICAM-1 by mAb YH384 was further
      confirmed by Northern blotting analysis at the mRNA level, and the maximal
      message of ICAM-1 was observed 4 hr after stimulation. mAb YH384-induced
      upregulation of cell surface expression was ICAM-1-specific, and the expression
      of the other nine molecules tested was not augmented. Up-regulation of ICAM-1 was
      also observed following stimulation with other mAb specific for CD11a (S6F1),
      CD11b (JML-H11), and CD18 (IB4); all of these mAb recognized members of the beta
      2-integrin family, but not with isotype-matched control mAb. The mAb 4B4
      (specific for beta 1-integrin) similarly, but more weakly, augmented ICAM-1
      expression. The effect of mAb YH384 on expression of ICAM-1 was dose-dependently
      suppressed by treatment with herbimycin A or genistein, both inhibitors of
      tyrosine kinase. These results suggest that beta 2-integrin-mediated up
      regulation of ICAM-1 is mediated via a tyrosine phosphorylation pathway.

PMID- 9184694
TI  - Failure of carcinogen-altered dendritic cells to initiate T cell proliferation is
      associated with reduced IL-1 beta secretion.
AB  - The activation of T cells through presentation of antigen by dendritic cells (DC)
      relies on many factors, including the correct balance of cytokines in the
      immediate microenvironment. Antigen presentation by DC migrating from carcinogen
      treated skin is impaired as evidenced by the failure of antigen-pulsed DC to
      initiate specific T cell proliferation. To elucidate mechanism(s) of DC
      dysfunction, DC migrating from carcinogen-treated skin were collected, pulsed
      with OVA, and cultured with antigen-specific autologous lymphocytes. Supernatants
      were assayed for the costimulatory cytokine IL-1 beta which influences the
      outcome of DC:T cell interactions. The dendritic cells migrating from carcinogen
      treated skin that failed to induce T cell proliferation were unable to produce IL
      1 beta. This may account for the abrogation of DC function following exposure to
      chemical carcinogens and provides an explanation for the inability of DC to
      induce a protective immune response to carcinogen-induced tumours.

PMID- 9184695
TI  - Treatment of subcutaneous tumor with adoptively transferred T cells.
AB  - Adoptive immunotherapy with T cells directed at tumor antigens has been
      demonstrated to result in the regression of malignant tumors in humans. These
      encouraging results have prompted the further exploration of parameters necessary
      to treat tumor in various locations in animal models. We have demonstrated that T
      cells that are sensitized to tumor antigens and then ex vivo cultured are capable
      of eradicating pulmonary metastases. In this report, we demonstrate that these T
      cells are capable of eliminating subcutaneous tumor deposits. Critical to the
      successful treatment of subcutaneous tumor was treatment with a large number of
      adoptively transferred T cells and pretreatment of the mice with irradiation. The
      transfer of T cells from tumor-bearing mice into irradiated mice failed to
      inhibit the therapeutic effect of ex vivo cultured T cells, suggesting that
      irradiation was not acting only as an immunosuppressant. Irradiation resulted in
      increased expression of the F4/80 and 33D1 epitopes on antigen-presenting cells
      within the tumor. The therapeutic effect of the adoptively transferred T cells
      was eliminated if either CD4 cells or CD8 cells were depleted. Naive T cells
      subjected to the same culture conditions were completely ineffective at
      eliminating tumor. These results demonstrate that adoptively transferred T cells
      derived from tumor-bearing hosts can treat subcutaneous tumor deposits, and they
      define the conditions necessary for the elimination of tumor in this location.

PMID- 9184696
TI  - The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated
      with changes in Bcl-2, Bcl-xL, and Mcl-1 expression.
AB  - Interleukin-10 (IL-10), a cytokine from mouse Th2 cells and macrophage that
      inhibits IL-2 and IFN-gamma production by Th1 cells, has been reported to
      stimulate growth and differentiation of B cells activated by CD40 or antigen
      receptor crosslinking. Our early observation revealed that IL-10 had B cell
      growth factor (BCGF) activity in human B cells preactivated with SAC or anti-Ig.
      The responsiveness of the preactivated B cells to IL-10 greatly increased when B
      cells were activated in the presence of IL-2, whereas IL-10 has no BCGF activity
      when added at the initiation of activation by SAC. To investigate the dual
      effects (proliferation and apoptosis) of IL-10 on B cells, the expression of a
      panel of bcl-2 protoncogene family members, bcl-2, bcl-x, mcl-1, and bax, was
      analyzed when B cells were activated by SAC. Bcl-xL protein was not expressed in
      the small resting B cells but was induced by SAC stimulation, reaching its peak
      at 48 hr. The addition of IL-2 further augmented the Bcl-xL expression with the
      same kinetics, whereas Bcl-2 and Mcl-1 were expressed by resting B cells and
      enhanced by SAC stimulation. However, the addition of IL-10 at the initiation of
      activation down-regulated Bcl-xL, Bcl-2, and Mcl-1 expression. At the same time,
      B cell proliferation was inhibited and apoptotic cell number increased,
      suggesting the growth arrest and/or apoptosis of B cells. The apoptosis of SAC
      activated B cells by IL-10 was further confirmed by propidium iodide-staining and
      Annexin V-FITC-staining methods. In contrast, IL-10 failed to down-regulate the
      Bcl-xL and Bcl-2 expression but rather augmented the expression of Mcl-1 of B
      cells after preactivation for 48 hr with SAC and IL-2. Under this culture
      condition, B cells responded to IL-10 to proliferate and differentiate, while IL
      2 and IL-10 had an additive or synergistic effect. Taken together, our data
      suggest that IL-10 acts on the induction stage of Bcl-xL expression and regulates
      the apoptosis and proliferation of SAC-activated B cells through their bcl-2
      family gene expression.

PMID- 9184697
TI  - Modeling the proliferative response of T cells to IL-2 and IL-4.
AB  - Interleukin (IL) -2 and IL-4 are growth factors for both T and B cells. When both
      cytokines are present, synergy is observed in some cases and antagonism in
      others. The studies presented here describe the use of a detailed mathematical
      model for the proliferative response of the T cell line, HT-2. This cell line
      responds to IL-2 and to IL-4 and shows a synergistic response when both cytokines
      are present. This model incorporates the observed synergy between these two
      cytokines while at the same time incorporating the known down-regulatory effect
      of IL-4 on the number of IL-2 receptors (IL-2R) at the cell surface, and it is
      able to reproduce a variety of experimental data. The major results from these
      studies include the following: the observation that the binding of IL-4 to its
      receptor is 1/10 as effective in delivering a proliferative signal as IL-2
      binding to its receptor, the determination of the threshold number of bindings
      required to signal proliferation stimulated by IL-2 and IL-4, the demonstration
      that many different sets of experimental data can be accurately modeled, and the
      use of simple parameter terms to model the synergy between IL-2 and IL-4.

PMID- 9184698
TI  - Altered kinetics of Tap-1 gene expression in macrophages following stimulation
      with both IFN-gamma and LPS.
AB  - With recent studies suggesting a key role for professional antigen presenting
      cells in the induction of major histocompatibility class I cellular immune
      responses, we initiated studies on the regulation of Tap-1 and Tap-2 gene
      expression in macrophages. Stimulation of the human macrophage cell line THP-1
      with interferon-gamma (IFN-gamma) resulted in maximal induction of both Tap-1 and
      Tap-2 mRNA within 24 hr. Nuclear run-on analyses showed that the increased
      expression of Tap-1 and Tap-2 was controlled at the level of transcription. Half
      life studies demonstrated that mRNAs for both genes became destabilized after
      stimulation of THP-1 cells with IFN-gamma for 24 hr, suggesting that a
      posttranscriptional mechanism down-regulates TAP gene expression following
      activation. Treatment of cells with both IFN-gamma and lipopolysaccharide (LPS)
      altered the kinetics and amount of Tap-1 mRNA and protein expression, compared to
      those with stimulation with IFN-gamma alone. These data suggest that LPS enhances
      the ability of macrophages stimulated with IFN-gamma to initiate a cellular
      immune response by altering the kinetics of TAP gene expression.

PMID- 9184699
TI  - Inductive events in oral tolerance in the TCR transgenic adoptive transfer model.
AB  - Oral administration of antigen induces a systemic hyporesponsiveness termed oral
      tolerance. High doses of oral antigen lead to deletion or anergy of T-cells
      whereas low doses induce regulatory T-cells that secrete Th2 cytokines (IL-4/IL
      10) and TGF-beta. The initiating events associated with oral tolerance have not
      been well characterized. We investigated the induction phase of oral tolerance by
      adoptively transferring ovalbulumin (OVA) p (323-339) TcR specific transgenic
      (Tg+) T-cells into BALB/c recipients that were then fed either a high (5 mg x 5)
      or a low (0.1 mg x 5) dose of OVA 323-329 peptide. The frequency of Tg+ T-cells
      in lymphoid tissues was determined by flow cytometry using an anti-clonotypic
      monoclonal antibody. In high-dose-fed animals, Tg+ cells increased six- to
      eightfold in Peyer's patches after one feeding and then progressively decreased
      to 44% of those in the control by Day 20. In contrast, a biphasic-type response
      was observed in lymph node and spleen where Tg+ cells decreased after the first
      feeding, returned to the control level, and then decreased to 36-63% of the
      control level by Day 20. In low-dose-fed animals, changes in Tg+ T cells were
      only observed in Peyer's patches after five feedings, where cells increased
      approximately twofold. T-cell activation as measured by proliferation and IFN
      gamma secretion occurred in both low- and high-dose-fed animals after only one
      feeding and then declined whereas secretion of Th2 cytokines and TGF-beta
      remained high even 10 days after the last feeding in low-dose-fed animals.
      Immunization with OVA/CFA demonstrated peripheral tolerance as measured by
      decreased proliferation and IFN-gamma secretion and was associated with increased
      production of TGF-beta and IL-10. These results suggest that the inductive phase
      of oral tolerance is characterized by an activation of antigen-specific T-cells
      that involves the initial secretion of IFN-gamma followed by prolonged secretion
      of Th2 cytokines and TGF-beta.

PMID- 9184700
TI  - Uveitogenicity is associated with a Th1-like lymphokine profile: cytokine
      dependent modulation of early and committed effector T cells in experimental
      autoimmune uveitis.
AB  - This study addresses the nature of the pathogenic effector T cell in experimental
      autoimmune uveoretinitis and the effect of different cytokines on these cells in
      vitro. Lymph node cells of B10.RIII mice immunized with the uveitogenic peptide
      161-180 of interphotoreceptor retinoid binding protein were cultured with the
      peptide with or without IL-12, IL-4, or anti-IL-4. An antigen-specific T cell
      line was subsequently derived from these cells. Primary cultures of immune lymph
      node cells stimulated with the peptide proliferated and produced IL-2 and some IL
      4, but no IFN-gamma. The addition of recombinant IL-12 resulted in abundant
      production of IFN-gamma, which was blocked by the addition of IL-4 and was
      enhanced by anti-IL-4. Only those cultures that produced IFN-gamma in vitro were
      uveitogenic in vivo. A long-term uveitogenic T cell line, initially derived in
      the presence of IL-12, produced IFN-gamma and IL-2, but not IL-4, and was CD4+
      (Th1-like). Antigen-specific proliferation and IFN-gamma production of the line
      were enhanced by exogenous IL-4, TGF-beta, IL-2, IL-6, IL-7, and IL-9 and were
      inhibited by IL-10 and TNF-alpha. Our results provide support for the hypothesis
      that the uveitogenic effector T cell has a Th1-like phenotype. Furthermore, the
      data suggest that the effects of the cytokine milieu on fully differentiated Th1
      effectors may differ considerably from their effects on less mature stages of
      antigen-specific T cells.

PMID- 9184701
TI  - Killing of rat adenocarcinoma 13762 in situ by adoptive transfer of CD4+ anti
      tumor T cells requires tumor expression of cell surface MHC class II molecules.
AB  - CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in
      vitro and cause regression of tumor in vivo. The role of various host immune
      cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by
      adoptive transfer of anti-tumor T cell clones to recipients that were selectively
      depleted of individual immune cell types. By these means, macrophages and NK
      cells were found to be required for tumor killing. Depletion of host CD4+ T
      cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by
      anti-tumor T cells. An essential role for antigen receptor-negative NK cells is
      likely dependent upon secretion of IFN-gamma from NK cells since treatment of
      tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and
      tumor challenge abrogated T cell killing, resulting in progressive tumor growth.
      Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by
      treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell
      surface MHC class II expression was induced in tumor cells by exposure to IFN
      gamma. In addition, tumor cells were isolated from tumor-bearing animals by
      absorption using anti-MHC class II antibody, demonstrating that 13762 tumor
      expresses cell surface MHC class II antigens in situ. However, if hosts were
      depleted of NK cells before tumor challenge, MHC class II+ tumor was not
      recovered. Collectively these results suggest that adenocarcinoma 13762 is
      eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

PMID- 9184702
TI  - Circulating CD8 T cells show increased interferon-gamma mRNA expression in HIV
      infection.
AB  - IFN-gamma mRNA levels were measured in unstimulated PBMC and purified cell
      subpopulations, utilizing branched DNA assays, to characterize the cell type(s)
      that contribute to the in vivo increase in IFN-gamma gene expression seen in HIV
      infection. PBMC and CD8 T cells from HIV-seropositive subjects (HIV+) showed 2.5
      fold increases in mean IFN-gamma mRNA levels compared to HIV-uninfected subjects
      (HIV-). Within individuals, CD8 T cells showed the highest IFN-gamma expression
      regardless of HIV status, which suggests that HIV infection enhances the IFN
      gamma gene expression in CD8 T cells rather than inducing a shift to and/or
      increasing expression of IFN-gamma mRNA in other cell types. HIV+ subjects with
      increased PBMC IFN-gamma mRNA had elevated plasma levels of HIV RNA, neopterin,
      and beta 2-microglobulin. No differences in IFN-gamma mRNA levels were seen among
      HIV+ stratified by CD4 T cell number. Increased IFN-gamma may result from or be a
      contributing factor to increased viral load.

PMID- 9184703
TI  - Short-term comparison of once- versus twice-daily administration of glimepiride
      in patients with non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To investigate the metabolic effects and frequency of adverse events
      with 6 mg of glimepiride, a new oral sulfonylurea, given both in once- and twice
      daily dosages to patients with non-insulin-dependent diabetes mellitus (NIDDM).
      RESEARCH DESIGN AND METHODS: This 15-week study involved 161 subjects with NIDDM.
      Subjects were randomized into two groups. For 4 weeks, group 1 received
      glimepiride 3 mg twice daily, and group 2 received glimepiride 6 mg once daily.
      After a 3-week placebo-washout period, twice- and once-daily regimens were
      crossed over for a second 4-week treatment period. Subjects were hospitalized at
      the end of each placebo or active-treatment phase. Their glucose concentrations
      were recorded at 20 time points over a 24-hour period, and their insulin and C
      peptide concentrations were recorded at 16 time points over the same period.
      Parameters that were calculated included fasting, 24-hour, and postprandial
      concentrations of glucose, insulin, and C-peptide. RESULTS: One hundred six
      patients were randomized to receive treatment; 94 completed the entire study.
      Existing physiologic mechanisms of glucose control were apparently unimpaired by
      glimepiride treatment. Insulin concentrations increased more during the
      postprandial glucose peaks than when subjects were fasting. Both twice- and once
      daily regimens proved equally effective in reducing concentrations of fasting,
      postbreakfast, postlunch, and postdinner plasma glucose. Twenty-four-hour mean
      glucose concentrations showed a slightly greater decrease from baseline for the
      twice-daily regimen; the difference between the regimens was statistically
      significant but not clinically meaningful. The incidence of adverse events with
      glimepiride approximated that obtained with placebo, with both groups reporting
      only one adverse event, headache, in more than 5% of the subjects. CONCLUSIONS:
      Glimepiride is equally effective whether administered once or twice daily.
      Glimepiride seems to stimulate insulin production primarily after meals, when
      plasma glucose concentrations are highest, but controls blood glucose throughout
      the day.

PMID- 9184704
TI  - Combination of low-dose niacin and pravastatin improves the lipid profile in
      diabetic patients without compromising glycemic control.
AB  - OBJECTIVE: To determine the efficacy and tolerability of the addition of low-dose
      niacin (1.5 g/d) in a diabetic hypercholesterolemic population who were unable to
      attain desired lipid control with low-dose (20 mg) pravastatin monotherapy.
      RESEARCH DESIGN AND METHODS: This was a prospective, open-label study conducted
      over a 14-week period. Twenty-three diabetic patients with low-density
      lipoprotein (LDL) cholesterol concentrations of at least 150 mg/dL after dietary
      therapy were recruited from the outpatient diabetes clinic of a university
      teaching hospital. After 4 weeks of dietary stabilization and baseline
      determination of the lipid profile and glycemic control, patients received
      pravastatin 20 mg once daily for 4 weeks. Laboratory parameters were reassessed
      and niacin was added to the regimen in qualifying patients. Over 2 weeks,
      patients' regimens were titrated to a maximal dosage of 500 mg tid. Patients
      continued to receive the combination regimen for 4 weeks and were reassessed.
      MEASUREMENTS AND MAIN RESULTS: Sixteen patients (14 non-insulin-dependent
      diabetes mellitus, 2 insulin-dependent diabetes mellitus) completed the study.
      Mean fasting blood sugar and fructosamine concentrations were unchanged
      throughout the study. Five patients required minor alterations (3 increased, 2
      decreased) in their hypoglycemic regimens during the study. The addition of low
      dose niacin to pravastatin therapy resulted in a significant lowering of LDL
      cholesterol compared with pravastatin monotherapy. CONCLUSIONS: Low-dose niacin
      is a promising addition to hydroxymethylglutaryl-coenzyme A reductase inhibitor
      therapy in the treatment of hypercholesterolemia in patients with diabetes
      mellitus.

PMID- 9184705
TI  - Efficacy and safety of intravenous phosphate replacement in critically ill
      patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous potassium phosphate
      administered in a fixed-dose regimen in critically ill patients. DESIGN:
      Prospective, unblind study. SETTING: Surgical-medical intensive care unit (ICU).
      PARTICIPANTS: Patients who developed hypophosphatemia during their ICU admission.
      INTERVENTIONS: Patients with a serum phosphate concentration between 1.27 and
      2.48 mg/dL (group 1) and those with a concentration of 1.24 mg/dL or less (group
      2) received 15 and 30 mmol, respectively, of phosphate as a potassium salt via a
      central line over 3 hours. MAIN OUTCOME MEASURES: Normalization of serum
      phosphate within 6 hours of infusion, the development of arrhythmias during the
      infusion, and the development of hypocalcemia and hyperkalemia after the infusion
      were evaluated. Redevelopment of hypophosphatemia and the need for further
      therapy were also assessed. RESULTS: Thirty-seven episodes of hypophosphatemia
      were entered in this study: 27 in group 1 (17 patients) and 10 in group 2 (10
      patients). The mean serum phosphate concentration increased significantly from
      2.02 to 2.82 mg/dL in group 1 and from 0.83 to 2.17 mg/dL in group 2, with no
      change in calcium or potassium. Normalization of serum phosphate with this
      initial dose occurred in 81.5% of the episodes in group 1 and 30% in group 2.
      However, over the following 2 days, 45% of the patients in group 1 and 60% in
      group 2 required further phosphate supplementation. No arrhythmias occurred
      during the 3-hour infusion that were related to the potassium phosphate. A
      significant drop in total serum calcium concentrations occurred in 2 patients who
      were slightly hypercalcemic prior to the infusion. Serum calcium concentrations
      remained above normal, but this was not associated with any adverse effects.
      CONCLUSIONS: The administration of potassium phosphate 15 mmol to critically ill
      patients with mild-to-moderate hypophosphatemia over 3 hours is both effective
      and safe. The administration of potassium phosphate 30 mmol to severely
      hypophosphatemic patients was safe but achieved normalization of serum phosphate
      in a minority of patients. Either a higher dose or the subsequent administration
      of more potassium phosphate may be required to normalize serum phosphate
      concentrations. Once normalization has occurred, there is a high likelihood of
      redevelopment of hypophosphatemia over the following 2 days and supplementation
      should be given accordingly.

PMID- 9184706
TI  - The effect of ICU sedation guidelines and pharmacist interventions on clinical
      outcomes and drug cost.
AB  - OBJECTIVE: To measure the effect of evidence-based intensive care unit (ICU)
      sedation guidelines and interventions by a pharmacist to promote these guidelines
      on the weaning time from mechanical ventilation and sedation drug cost. DESIGN:
      Before-after study. SETTING: A 15-bed medical-surgical ICU at a tertiary-care
      teaching hospital. PATIENTS: 100 patients (2 groups of 50 consecutive patients)
      on mechanical ventilation (assist or pressure control mode for > or = 6 h) who
      were successfully discharged from the ICU. METHODS: ICU sedation guidelines were
      developed through physician, nursing, and pharmacy consensus using a physician
      survey and literature overview as points of reference and were implemented into
      practice. Prospectively, data on the time required to wean patients from
      mechanical ventilation (successful trial of T-piece, pressure support, or
      intermittent mandatory ventilation leading to extubation) and total drug costs
      for sedation were measured and compared between groups. All prospective ICU
      pharmacist interventions pertaining to sedation were documented. RESULTS: New
      sedation guidelines promoted lorazepam use in preference to midazolam and
      suggested propofol for patients not successfully sedated with high-dose
      lorazepam, haloperidol, or morphine. Over the 2-month collection periods, there
      was no difference in the median weaning time between the pre- (16 h, range 2-607)
      and post- (18 h, range 1-284) guideline groups. Total sedation drug costs
      decreased from $4515 to $1152 ($US) (p = 0.081). Median sedation drug costs
      decreased from $11.27 (range $0-1340) to $3.55 (range $0-250), with the amount
      (mg) of midazolam and propofol used decreasing by 86% and 100%, respectively. The
      ICU pharmacist successfully recommended a change from midazolam to lorazepam in
      12 of 50 patients, 5 of whom had received midazolam for more than 24 hours.
      CONCLUSIONS: High compliance with ICU sedation guidelines promoting lorazepam
      rather than midazolam or propofol in mechanically ventilated patients led to a
      75% decrease in sedation drug costs and did not adversely affect the clinicians'
      ability to wean patients from mechanical ventilation.

PMID- 9184707
TI  - Assessment of the enzymuria resulting from gentamicin alone and combinations of
      gentamicin with various beta-lactam antibiotics.
AB  - OBJECTIVE: To determine the propensity of beta-lactam antimicrobials to
      ameliorate or potentiate aminoglycoside-induced renal enzymuria. DESIGN: Two
      open, randomized, double-blind, parallel-group studies were conducted in young,
      healthy, male volunteer subjects. Using a common protocol, 24-hour urine
      collections were analyzed for the renal tubular enzymes alanine aminopeptidase
      (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as for creatinine.
      Antimicrobial combinations studied included gentamicin plus placebo and
      gentamicin plus ticarcillin/clavulanate (protocol 1); and gentamicin plus
      placebo, gentamicin plus piperacillin, and gentamicin plus ceftazidime (protocol
      2). The antimicrobial regimens were administered for 7 days. Eight subjects
      completed each treatment group. RESULTS: There were no significant differences
      between treatment groups with regard to urine creatinine excretion or serum
      gentamicin concentrations in either protocol. Enzymuria (AAP [p = 0.039] and NAG
      [p = 0.337]) was decreased in the gentamicin plus ticarcillin/clavulanate
      treatment compared with that in the gentamicin plus placebo treatment. Increased
      enzymuria, as indicated by increased urine concentrations of AAP and NAG, was
      observed in the gentamicin plus ceftazidime treatment (p < 0.05) compared with
      the other two treatments. CONCLUSIONS: Based on relative enzymuria,
      ticarcillin/clavulanate may be renal protective. Piperacillin neither potentiated
      nor ameliorated aminoglycoside-induced enzymuria. Since acute elevations in AAP
      and NAG reflect insults to the kidney, these studies suggest that ceftazidime may
      enhance aminoglycoside-induced renal injury. Piperacillin had no effect on
      enzymuria and would appear not to enhance or protect against aminoglycoside
      induced renal injury.

PMID- 9184708
TI  - Isradipine therapy in hypertensive pediatric patients.
AB  - OBJECTIVE: To evaluate the dosage and effectiveness of isradipine to control
      acute or chronic hypertension in pediatric patients. DESIGN: Retrospective
      medical record review. SETTING: University teaching hospital. PARTICIPANTS:
      Hospitalized pediatric patients aged 1 day to 16 years with hypertension treated
      with isradipine between January 1994 and March 1996. MEASURES: Patient age,
      gender, weight, disease states, current medications, isradipine dosage and
      formulation, pre- and postsystolic, and pre- and postdiastolic blood pressure
      measurements with each dose of isradipine. RESULTS: Fifty-three patients with a
      mean age of 5.8 +/- 4.0 years were evaluated. A mean change in the blood pressure
      measurements taken before the first dose of isradipine compared with the values
      recorded after the last dose or at discharge for all patients was -11.8% +/-
      12.5% and -17.4% +/- 19.6%, respectively, for systolic and diastolic pressure.
      The mean dosage of isradipine in 46 patients who received regularly scheduled
      doses was 0.38 +/- 0.22 mg/kg/d. Patients who demonstrated a response received a
      mean dosage of 0.40 +/- 0.20 mg/kg/d. The total daily dosage was administered in
      one dose for 1 patient, two doses for 15 patients, three doses for 27 patients,
      and four doses for 3 patients. CONCLUSIONS: Isradipine was an effective
      antihypertensive agent to reduce the systolic and/or diastolic blood pressure 10%
      or more compared with pretreatment measurements in 43 (81%) of 53 pediatric
      patients. The mean dosage was 0.38 +/- 0.22 mg/kg/d, most frequently administered
      in two or three equally divided doses, which is higher than the normal
      recommended dosage for adults.

PMID- 9184709
TI  - The use of alternate-day lovastatin in hypercholesterolemic men.
AB  - OBJECTIVE: To quantitate the therapeutic effects of alternate-day lovastatin on
      serum lipoprotein values in a small group of men with primary
      hypercholesterolemia. DESIGN: Retrospective review of medical, pharmacy, and
      laboratory records. A paired Student's t-test was performed on absolute changes
      in lipoprotein values with an a priori p value less than or equal to 0.05 being
      statistically significant. SETTING: A lipid clinic within a tertiary care
      Department of Veterans Affairs Medical Center. PATIENTS: Twenty men (mean age
      62.5 +/- 8.3 y) with mean +/- SD baseline low-density lipoprotein cholesterol
      (LDL-C) concentration of 161.3 +/- 21.9 mg/dL and triglyceride concentrations
      below 400 mg/dL. INTERVENTION: All patients had been prescribed lovastatin 20 mg
      every other day. MAIN OUTCOME MEASURES: The mean absolute and percent changes in
      lipoprotein values from baseline for patients receiving lovastatin 20 mg every
      other day and the percentage of patients attaining a target mean LDL-C
      concentration as defined by the National Cholesterol Education Panel Adult
      Treatment Panel II guidelines. RESULTS: Mean +/- SD total cholesterol and LDL-C
      were significantly reduced by 32.4 +/- 17.8 (14.0% +/- 7.8%) and 34.1 +/- 14.6
      mg/dL (21.5% +/- 9.7%), respectively. No significant changes were seen in high-
      density lipoprotein cholesterol or triglycerides. Four of 20 patients (20%)
      attained a goal LDL-C concentration. CONCLUSIONS: Lovastatin 20 mg every other
      day may effectively lower LDL-C in some elderly men, and target LDL-C
      concentrations may be obtained in some patients.

PMID- 9184710
TI  - Implementation of pharmaceutical care services for patients with hyperlipidemias
      by independent community pharmacy practitioners.
AB  - OBJECTIVE: To implement and evaluate pharmaceutical care services for patients
      with hyperlipidemias in the community pharmacy setting, to evaluate the results
      of a pharmaceutical care training process for pharmacists by using an assessment
      quiz, and to measure patient outcomes resulting from provision of pharmaceutical
      care to patients with hyperlipidemia. DESIGN: A prospective study was conducted
      over a 1-year period. Patients served as their own controls. SETTING: Two
      independent community pharmacies in Richmond, Virginia. PARTICIPANTS: Twenty-five
      adult patients with confirmed dyslipidemias completed the study. INTERVENTIONS:
      Study pharmacists assessed each patient and assisted in setting therapeutic
      goals; patients also completed a visit with a registered dietitian. Drug therapy
      recommendations were made to physicians by the pharmacist when appropriate.
      Follow-up was scheduled with the pharmacist to ensure positive outcomes and
      reduce adverse effects. MAIN OUTCOME MEASURES: Fasting lipoprotein profiles were
      measured initially and at 6 and 12 months. The SF-36 survey, the MacKeigan-Larson
      satisfaction survey, and a patient opinion survey were administered initially and
      at the conclusion of the study. RESULTS: Total cholesterol and low-density
      lipoprotein cholesterol values were significantly decreased at 12 months compared
      with either the baseline or 6-month values (p < 0.02). Significant improvement
      was found in several domains of the surveys; quality of life, patient
      satisfaction with pharmacy services, and patient opinions on the role of the
      pharmacist improved after the intervention. CONCLUSIONS: Pharmaceutical care may
      positively affect lipid values, quality of life, and patient satisfaction.

PMID- 9184711
TI  - Suspected lamotrigine-induced toxic epidermal necrolysis.
AB  - OBJECTIVE: To describe a patient who developed toxic epidermal necrolysis (TEN)
      possibly secondary to lamotrigine use. CASE SUMMARY: A 74-year-old white man with
      a history of probable complex partial seizures was admitted to the neurology
      service for a prolonged postictal state. His antiepileptic regimen was changed
      while he was in the hospital to include lamotrigine. After 19 days of
      hospitalization and 14 days of lamotrigine therapy, the patient became febrile.
      The next day he developed a rash which progressed within 4 days to TEN, diagnosed
      by skin biopsy. All suspected drugs were discontinued, including lamotrigine. The
      patient was treated with hydrotherapy in the burn unit. His symptoms improved and
      he was discharged from the hospital 26 days after the rash developed. DISCUSSION:
      During lamotrigine's premarketing clinical trials, the manufacturer reported
      several cases of Stevens-Johnson syndrome and TEN. There are several published
      case reports of lamotrigine-induced severe skin reactions. All of these reports
      included patients being treated with both valproic acid and lamotrigine. Our
      patient was exposed to phenytoin, carbamazepine, clindamycin, and lamotrigine,
      but not valproic acid. The patient reported prior use of phenytoin with no skin
      rash. Carbamazepine was the antiepileptic drug the patient was maintained on
      prior to his hospital admission, and the symptoms of TEN resolved while he was
      still receiving carbamazepine. The patient received only two doses of
      clindamycin, which makes this agent an unlikely cause of TEN. CONCLUSIONS:
      Because of the temporal relationship of the onset of the patient's rash and
      several drugs that are known to cause severe rashes, it is not certain which drug
      was the definite culprit. However, based on the evidence from the literature,
      lamotrigine appears to be the causative agent.

PMID- 9184712
TI  - Pancreatic insufficiency due to antituberculous therapy.
AB  - OBJECTIVE: To describe a case of chronic pancreatic insufficiency related to
      antituberculous therapy. CASE SUMMARY: A 57-year-old man developed rash, fever,
      and hepatitis (aspartate aminotransferase 369 IU/L, alanine aminotransferase 506
      IU/L), 6 weeks after starting isoniazid, rifampin, ethambutol, and pyrazinamide.
      He also developed severe metabolic acidosis secondary to diabetic ketoacidosis
      and lactic acidosis (serum bicarbonate 7 mEq/L, glucose 1778 mg/dL, and lactate
      4.0 mEq/L). Acute pancreatitis was diagnosed on the basis of a mildly elevated
      amylase concentration (392 U/L) and radiologic evidence of pancreatic
      inflammation. He developed pancreatic insufficiency with steatorrhea and an
      abnormal secretin test. He continues to require pancreatic enzyme replacement and
      insulin therapy. Rechallenge was not performed. DISCUSSION: Hypersensitivity
      syndromes have been reported for various drug therapies, including
      antituberculous agents. Hypersensitivity syndrome reactions are characterized by
      fever, rash, and internal organ involvement. Rifampin has been reported to cause
      acute pancreatitis in up to 2.7% of patients. Drug-induced chronic pancreatitis,
      however, is reported to be extremely rare. This is the first reported case of
      chronic pancreatic insufficiency occurring in the setting of a hypersensitivity
      syndrome reaction to antituberculous drugs. CONCLUSIONS: Chronic pancreatic
      insufficiency should be considered as a possible long-term sequelae of a
      hypersensitivity syndrome reaction to antituberculous therapy.

PMID- 9184713
TI  - Trimethoprim/sulfamethoxazole-induced hypoglycemia in a patient with acute renal
      failure.
AB  - OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced
      hypoglycemia in a patient with acute renal failure. DATA SOURCES: English
      language references identified via a MEDLINE search from January 1966 to August
      1996 and a bibliographic review of pertinent articles. DATA SYNTHESIS: Similar to
      sulfonylureas, sulfonamides are thought to cause hypoglycemia by increasing
      pancreatic secretion of insulin. To date, nine cases of TMP/SMX-induced
      hypoglycemia have been reported in the literature. This case represents the
      second report in which a patient experienced TMP/SMX-induced hypoglycemia that
      resolved after the dosage was adjusted for the patient's decreased renal
      function. This case involved a 73-year-old comatose white man initiated on high
      dose TMP/SMX for nosocomial pneumonia caused by Stenotrophomonas maltophilia.
      After 5 days of therapy, the patient presented with severe hypoglycemia that
      persisted over 8 hours despite multiple intravenous bolus doses and infusions of
      dextrose. The patient had several risk factors that may have compounded his risk
      for hypoglycemia, including food deprivation and acute renal failure. After
      management with dextrose and dose adjustment of the patient's TMP/SMX regimen
      according to renal function, the hypoglycemia resolved. CONCLUSIONS: TMP/SMX may
      cause reversible hypoglycemia that may be prolonged (approximately 12 h),
      particularly in patients with risk factors for hypoglycemia. Common risk factors
      include compromised renal function, prolonged fasting conditions, malnutrition,
      and the use of excessive doses. Patients with these risk factors should be
      monitored closely and, more importantly, initiated on a dosing regimen adjusted
      for renal impairment.

PMID- 9184714
TI  - Severe minocycline-induced eosinophilic pneumonia: extrapulmonary manifestations
      and the use of in vitro immunoassays.
AB  - OBJECTIVE: To report a severe and unusual reaction to minocycline and the use of
      in vitro immunologic assays. CASE SUMMARY: A 46-year-old white man developed
      severe respiratory distress with pulmonary infiltrates on chest X-ray and
      eosinophilia in blood, bronchoalveolar lavage fluid, and biopsied lung tissue
      during exposure to minocycline. Additional manifestations included
      pleuropericardial effusion, liver function abnormality, and bone marrow
      eosinophilia. Macrophage inhibition factor and mast cell degranulation assays
      were positive to minocycline. DISCUSSION: The patient's manifestations were
      compatible with the diagnosis of eosinophilic pneumonia. After excluding other
      possible etiologies, minocycline was identified as the offending agent.
      Generalized damage was suggested by the presence of a combination of
      extrapulmonary manifestations previously not reported. Results of the in vitro
      immunologic assays supported the hypersensitivity nature of the disease and
      confirmed the diagnosis. CONCLUSIONS: Minocycline-induced eosinophilic pneumonia
      may involve extrapulmonary sites. It is suggested that in vitro immunoassays be
      used for confirmation of the diagnosis rather than rechallenge or invasive
      procedures.

PMID- 9184715
TI  - Possible toxic encephalopathy following high-dose intravenous haloperidol.
AB  - OBJECTIVE: To describe a case of possible toxic encephalopathy in a surgical
      patient receiving high-dose intravenous haloperidol. CASE SUMMARY: A 54-year-old
      African-American man was admitted for spinal fusion. His medical history included
      bipolar disorder and a cerebrovascular accident. His recovery from surgery was
      complicated by the development of agitation, which was treated with increasing
      doses of intravenous haloperidol. An electroencephalogram was consistent with
      toxic encephalopathy. The patient's mental status returned to normal 8 days after
      discontinuation of haloperidol. DISCUSSION: High-dose intravenous haloperidol for
      severe agitation has been reported as an effective and safe treatment option for
      the hospitalized patient. We report the occurrence of toxic encephalopathy in a
      patient who received high-dose intravenous haloperidol. CONCLUSIONS: Caution
      should be used when high-dose intravenous haloperidol is used in an agitated
      patient. If the patient's clinical response is paradoxical to what is anticipated
      and the resulting agitation is mistakenly attributed to inadequate treatment,
      increasingly higher doses may only aid in the development of toxic
      encephalopathy.

PMID- 9184716
TI  - Riluzole: a new agent for amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To provide a comprehensive review of riluzole, including its mechanism
      of action, pharmacokinetics, adverse drug reactions, drug interactions, efficacy,
      and administration. A brief review of amyotrophic lateral sclerosis (ALS) is also
      included. DATA SOURCES: A computerized search of the MEDLINE database in May 1996
      was used to identify publications regarding ALS, riluzole, and metabolism by
      CYP1A2. Manufacturer's information on riluzole was used when there was no primary
      literature. DATA SYNTHESIS: Riluzole is approximately 90% absorbed following an
      oral dose. Its bioavailability is 60%. Peak concentrations occur within 1-1.5
      hours of administration. Riluzole extensively binds to lipoproteins and albumin.
      This agent primarily undergoes CYP1A2 hydroxylation and glucuronidation, after
      which it is eliminated by the kidneys. Clearance is reduced in native Japanese
      healthy subjects and may be reduced in patients with hepatic impairment. Two
      trials with a total of 1114 patients addressed the efficacy of riluzole in ALS.
      Riluzole extended the time to tracheostomy or death, and the effect was greatest
      with dosages of 100 mg/d or greater. No effect on patients' symptoms or global
      assessment was detected at 18 or 21 months. Several flaws in these trials have
      led to questions concerning the validity of these results. The most commonly
      reported adverse effects of riluzole have been transient elevation of liver
      enzyme concentrations (2-5 times the upper limit of normal), worsening of
      asthenia, nausea, vomiting, diarrhea, anorexia, dizziness, vertigo, somnolence,
      and mouth paresthesia. Not as commonly reported, but still very serious, is
      neutropenia, which occurred in 3 of 4000 patients. CONCLUSIONS: Although the
      benefits of riluzole are questionable and it is expensive, this agent may extend
      the time to tracheostomy or death in patients with ALS. At present, this is the
      only agent approved for the treatment of ALS and should be made available for
      these patients.

PMID- 9184717
TI  - Controversies surrounding estrogen use in postmenopausal women.
AB  - OBJECTIVE: To provide an overview of controversies regarding the use of estrogen
      in postmenopausal women. DATA SOURCES: A MEDLINE search was conducted to identify
      pertinent literature published since 1990. Recently published textbooks devoted
      to the subjects of menopause and women's health were also reviewed, particularly
      their bibliographies. The bibliographies of selected review articles were also
      reviewed. STUDY SELECTION: Due to the vast amount of literature, only the most
      relevant published studies were reviewed. Review articles and book chapters
      authored by researchers of international reputation were also reviewed. DATA
      EXTRACTION: Identified studies from the primary literature and selected reviews
      were carefully reviewed. Information regarding the use of estrogen in
      postmenopausal women was extracted. Particular attention was given to areas of
      controversy commonly dealt with in the lay media. DATA SYNTHESIS: The number of
      postmenopausal women in the US will approach 60 million in the next decade.
      Despite numerous potential benefits, many women elect to not take estrogen due to
      fear of cancer or poor understanding of the long-term consequences of menopause
      and the beneficial effects of estrogen replacement therapy. Many women rely on
      the news media for information about hormone therapy and subsequently become
      confused regarding the benefits and risks. Estrogen relieves climacteric symptoms
      such as hot flushes and symptoms related to genitourinary tissue atrophy.
      Outcomes from controlled clinical trials are lacking, but numerous epidemiologic
      studies document clinically significant decreases in cardiovascular disease and
      osteoporotic morbidity and mortality. Unopposed estrogen increases the risk for
      endometrial cancer, but addition of a progestin for at least 10 days per cycle
      effectively reduces this risk to that of women who do not take estrogen. The
      association between postmenopausal estrogen use and breast cancer remains
      controversial, despite the results of numerous observational studies. This
      uncertainty regarding estrogen replacement and breast cancer risk can actually be
      reassuring when placed in proper perspective. CONCLUSIONS: Until some of the
      controversies surrounding postmenopausal hormone use are resolved, an objective
      discussion with a knowledgeable healthcare professional regarding the potential
      benefits and risks will help women make informed decisions regarding estrogen
      replacement therapy in the postmenopausal years.

PMID- 9184718
TI  - Automated peritoneal dialysis: new implications for pharmacists.
AB  - OBJECTIVE: To review the new automated peritoneal dialysis (APD) modalities that
      are available to patients with end-stage renal disease (ESRD), and to examine
      their potential pharmacokinetic and drug dosing consequences. DATA SOURCES: A
      MEDLINE search (from January 1966 to June 1996) of English-language literature
      pertaining to peritoneal dialysis was performed. Additional references were
      obtained by reviewing the references of pertinent articles identified through the
      search. Tertiary sources were also used. DATA EXTRACTION: Data regarding
      peritoneal dialysis techniques and pharmacokinetics were extracted from the
      literature. Data were evaluated according to the study design, population,
      results, and conclusions. DATA SYNTHESIS: ESRD is the result of progressive
      chronic renal insufficiency and requires renal replacement therapy. APD is the
      fastest growing renal replacement therapy by percentage in the US and provides
      dialysis exchanges via a machine while the patient sleeps, thereby improving
      patient convenience, peritoneal dialysis compliance rates, and decreasing
      peritonitis rates. Well-designed pharmacokinetic studies involving APD have not
      been conducted. Consequently, no formal drug dosing recommendations are available
      for APD, and pharmacists must rely on established dosing guidelines for
      continuous ambulatory peritoneal dialysis (CAPD) when recommending dosing
      regimens. This article describes the new APD treatment modalities available and
      the potential pharmacokinetic differences between CAPD and APD. CONCLUSIONS: Well
      designed studies are needed to fully characterize the pharmacokinetic parameters
      of drugs in APD. Until then, pharmacists should recommend that intraperitoneally
      administered drugs be given during the longest peritoneal dialysate dwell of the
      day and that serum concentrations of drugs with narrow therapeutic indices be
      monitored closely.

PMID- 9184720
TI  - Ticlopidine and aspirin therapy following implantation of coronary artery stents.
AB  - A number of studies evaluated the pharmacologic management of patients with
      coronary artery stents. Four studies demonstrated a low subacute thrombosis rate
      with antiplatelet therapy without implementation of anticoagulant therapy.
      However, in three of these trials conflicting results were reported regarding the
      relative efficacy of various antiplatelet therapies. Given the limitations of
      these studies, well-designed, randomized studies are necessary to assess the
      relative superiority of antiplatelet regimens to determine the safest and most
      effective treatment. Two clinical studies evaluated antiplatelet therapy compared
      with anticoagulant therapy in patients receiving coronary artery stents. Compared
      with conventional anticoagulant therapy, combined antiplatelet therapy with
      ticlopidine and aspirin appears to reduce clinical cardiovascular events, stent
      thrombosis, and hemorrhagic complications. Despite the potential benefits of
      therapy with ticlopidine observed in these studies, hematologic monitoring is
      required to detect neutropenia that may occur during ticlopidine therapy. In
      addition, the potential benefits of combination therapy with ticlopidine and
      aspirin apply only to patients at low risk as defined by the ACCP and ACC expert
      panels. Until further data become available, high-risk patients should be managed
      with conventional anticoagulation regimens. Studies are needed to determine
      whether antiplatelet therapy is effective in high-risk patients and the optimal
      antiplatelet therapy (ticlopidine, aspirin, or ticlopidine/aspirin) for the
      management of patients with coronary artery stents.

PMID- 9184719
TI  - Pharmaceutical education: roots and branches. Rho Chi Lecture Award.

PMID- 9184721
TI  - Cromolyn sodium for ACE inhibitor-induced cough.
AB  - There are several theories on the cause of ACE inhibitor-induced cough, but the
      exact mechanism is not known. In many patients, if cough develops, the ACE
      inhibitor can be discontinued and a drug in another therapeutic class used in its
      place. However, in patients with CHF, diabetic nephropathy, and patients who have
      experienced a myocardial infarction, discontinuing the ACE inhibitor may not be
      in the best interest of the patient. In this patient population it would be
      reasonable to try cromolyn sodium to treat cough, while continuing the ACE
      inhibitor. Data are not available to support the efficacy of cromolyn sodium to
      treat cough in patients with diabetic nephropathy, but these patients clearly
      benefit from the use of an ACE inhibitor. Other factors not addressed in the case
      reports and the clinical trial such as patient adherence, cost, and quality of
      life should also play a role in the decision to use cromolyn sodium. Cromolyn
      sodium has been effective for the treatment of ACE inhibitor-induced cough in
      many case reports and has had mild success in one small clinical trial. Although
      none of the reports adequately assessed adverse effects, studies examining
      cromolyn for other indications have demonstrated a relatively benign adverse
      effect profile. It is difficult to recommend an exact dose to use because of the
      dosing variability in the case reports. The majority of the case reports and the
      one clinical trial used dosages similar to recommendations for bronchial asthma
      (i.e., 2 puffs [1.6 mg] 4 times daily via MDI or 20-mg capsules 4 times daily via
      breath-activated inhalation). At this time, the use of cromolyn sodium is a
      viable option, but more controlled studies are needed to fully elucidate its role
      in the treatment of ACE inhibitor-induced cough.

PMID- 9184722
TI  - Risks of infection or reactivation of tuberculosis associated with chronic
      corticosteroid therapy.
AB  - Although corticosteroids are known to be immunosuppressive, there have been no
      studies to show that use of corticosteroids increases the risk of developing new
      tuberculosis or reactivating old tuberculosis. In fact, corticosteroids are
      recommended for the treatment of several forms of tuberculosis, such as pleural
      tuberculosis, genitourinary tuberculosis, and tuberculous meningitis. Clinicians
      should still be alert for tuberculosis appearing in immunocompromised patients as
      a disseminated infection or for tuberculosis that is atypical in appearance.

PMID- 9184723
TI  - Medroxyprogesterone acetate in the treatment of obstructive sleep apnea.
AB  - The use of MPA in patients with OSA is limited. Instead, patients with OSA should
      be encouraged to abstain from alcohol and respiratory depressive agents, and
      avoid sleeping in the supine position. In general, patients with OSA are most
      effectively treated with CPAP and/or surgery. Patients need to be encouraged to
      maintain ideal body weight, since this has been associated with a marked
      reduction in symptoms. For patients who are not surgical candidates or refuse to
      use CPAP, drug therapy may be beneficial. Fluoxetine has been shown to be as
      effective as protriptyline, and is better tolerated. However, further study is
      needed to determine whether selective serotonin-reuptake inhibitors are
      beneficial in treating OSA. Therefore, MPA therapy should be reserved for
      hypercapnic patients who refuse other modalities of treatment. The potential long
      term adverse effects of MPA must be addressed before initiating therapy in men
      with OSA.

PMID- 9184724
TI  - Riluzole--what is its impact in our treatment and understanding of amyotrophic
      lateral sclerosis?
AB  - Riluzole marks the beginning of pharmacotherapy for patients with ALS. Our task
      is to fully identify the impact of riluzole in ALS treatment. The ALS Clinical
      Assessment Research and Education (ALS CARE) is an ambitious database in North
      America created to establish the benchmarks for patient care and management. Such
      a program may allow us to analyze the use and impact of riluzole in the treatment
      of ALS. In the spring of 1997, just 1 year since the approval of riluzole,
      several more potential drugs for ALS are on the horizon. If a single medication
      is not sufficient to alter the disease course significantly, we must investigate
      drug combinations to determine potential additive or synergistic benefits.
      Although far from ideal, riluzole is allowing clinicians and researchers to lift
      a corner of the veil surrounding ALS to glimpse the possibility of effective
      treatment.

PMID- 9184725
TI  - Depression in primary care: review of AHCPR guidelines.
AB  - OBJECTIVE: To present an overview and evaluation of the Agency for Health Care
      Policy and Research (AHCPR) clinical practice guidelines for the treatment of
      depression. INTRODUCTION: One responsibility of the AHCPR is the development and
      periodic review and update of clinical practice guidelines. This process is
      undertaken by an independent panel composed of groups of clinicians and other
      experts from the private sector. Their findings are published in a four-volume,
      softcover set of booklets. DATA SOURCE AND EVALUATION: Volume 2 in the four
      volume set includes a comprehensive complication, synthesis, and critical
      evaluation of the studies of different treatments for depression. Studies
      included for evaluation were randomized, prospective clinical trials that were
      pertinent to all topics concerning the treatment of depression. In some areas,
      the opinions of the panel were included due to a paucity of data from well
      controlled clinical trials. Each AHCPR guideline was followed by a code that
      indicated whether the strength of evidence supporting that guideline was based on
      good or fair research-based evidence, or whether it was based primarily on panel
      members' opinions. CONCLUSIONS: With regard to drug treatment, the guidelines are
      good. However, since these guidelines were published in 1993 they might be
      considered somewhat dated because more antidepressants have become available in
      the interim. Overall, the AHCPR guidelines reflect an extensive review of the
      literature provided by the panel, as well as input from a highly respected group
      of reviewers. The panel included physicians, a nurse, a social worker, a
      psychologist, and a consumer representative. Unfortunately, a pharmacist was not
      included on the panel. Input from pharmacy practitioners would have been
      valuable.

PMID- 9184727
TI  - Clarithromycin-induced fever in a patient with Helicobacter pylori gastritis.

PMID- 9184726
TI  - Costs and outcomes associated with colfosceril versus beractant for the treatment
      of neonatal respiratory distress syndrome.

PMID- 9184728
TI  - The road to academic success is paved with blood, sweat, and tears.

PMID- 9184729
TI  - Compatibility of hydromorphone and prochlorperazine, and irritation due to
      subcutaneous prochlorperazine infusion.

PMID- 9184730
TI  - Potential warfarin-fluvastatin interaction.

PMID- 9184731
TI  - Comment: seizure resulting from venlafaxine overdose.

PMID- 9184732
TI  - Aviation spatial orientation in relationship to head position and attitude
      interpretation.
AB  - BACKGROUND: Conventional wisdom describing aviation spatial awareness assumes
      that pilots view a moving horizon through the windscreen. This assumption
      presupposes head alignment with the cockpit "Z" axis during both visual (VMC) and
      instrument (IMC) maneuvers. Even though this visual paradigm is widely accepted,
      its accuracy has not been verified. The purpose of this research was to determine
      if a visually induced neck reflex causes pilots to align their heads toward the
      horizon, rather than the cockpit vertical axis. HYPOTHESIS: Based on literature
      describing reflexive head orientation in terrestrial environments it was
      hypothesized that during simulated VMC aircraft maneuvers, pilots would align
      their heads toward the horizon. METHODS: Some 14 military pilots completed two
      simulated flights in a stationary dome simulator. The flight profile consisted of
      five separate tasks, four of which evaluated head tilt during exposure to unique
      visual conditions and one examined occurrences of disorientation during unusual
      attitude recovery. RESULTS: During simulated visual flight maneuvers, pilots
      tilted their heads toward the horizon (p < 0.0001). Under IMC, pilots maintained
      head alignment with the vertical axis of the aircraft. CONCLUSION: During VMC
      maneuvers pilots reflexively tilt their heads toward the horizon, away from the
      Gz axis of the cockpit. Presumably, this behavior stabilizes the retinal image of
      the horizon (1 degree visual-spatial cue), against which peripheral images of the
      cockpit (2 degrees visual-spatial cue) appear to move. Spatial disorientation,
      airsickness, and control reversal error may be related to shifts in visual
      vestibular sensory alignment during visual transitions between VMC (head tilt)
      and IMC (Gz head stabilized) conditions.

PMID- 9184733
TI  - Aviation spatial orientation in relationship to head position, altitude
      interpretation, and control.
AB  - INTRODUCTION: Recently, a visually driven neck reflex was identified as causing
      head tilt toward the horizon during VMC flight. If this is the case, then pilots
      orient about a fixed rather than moving horizon, implying current attitude
      instruments inaccurately present spatial information. The purpose of this study
      was to determine if the opto-kinetic cervical neck reflex has an effect dependent
      on passive (autopilot) or active control of the aircraft. Further, findings could
      help determine if the opto-kinetic cervical reflex is characteristic of other
      flight crewmembers. METHODS: There were 16 military pilots who flew two 13-min
      VMC low-level routes in a large dome flight simulator. Head position in relation
      to aircraft bank angle was recorded by a head tracker device. During one low
      level route, the pilot had a supervisory role as the autopilot flew the aircraft
      (passive). The other route was flow manually by the pilot (active). RESULTS:
      Pilots consistently tilted the head to maintain alignment with the horizon.
      Similar head tilt angles were found in both the active and passive flight phases.
      However, head tilt had a faster onset rate in the passive condition. CONCLUSION:
      Results indicate the opto-kinetic cervical reflex affects pilots while actively
      flying or in a supervisory role as the autopilot flies. The consistent head tilt
      angles in both conditions should be considered in attitude indicator, HUD, and
      HMD designs. Further, results seem to indicate that non-pilot flight crewmembers
      are affected by the opto-kinetic cervical reflex which should be considered in
      spatial disorientation and airsickness discussions.

PMID- 9184735
TI  - Ventilatory capacities at sea level and high altitude.
AB  - Because air is less dense at high altitude (HA), airway resistance is reduced and
      maximum inspiratory and expiratory flows are greater than at sea level (SL).
      Despite the reduction in airway resistance, ventilatory muscle endurance may be
      decreased by hypobaric hypoxia and, thus, may be a factor in limiting exercise at
      HA. To explore the effects of HA on ventilatory capacities and their relation to
      ventilatory demands of exercise, we measured 15-s maximum voluntary ventilation
      (MVV), 15-min maximum sustainable ventilation (MSV), and maximum airway pressures
      (Plmax and PEmax) in 18 healthy young men at SL and HA (Pikes Peak, 4300 m, or
      hypobaric chamber, PB approximately 460 mmHg). In eight of these subjects
      ventilatory capacities were compared with exercise ventilations. We also measured
      the effects of 36% O2 on the MSV in 12 of the subjects exposed to simulated
      altitude. Similar results were obtained at either simulated or actual HA. We
      found that MVV increased (p < 0.001) by 20% and the MSV (p < 0.001) by 15% at HA.
      Administration of 36% O2 at HA increased MSV further by 5% with no effect on MVV.
      No effect of HA on maximum inspiratory and expiratory pressures was found. We
      confirmed previous findings of modest increases in forced 1-s expired volume
      (FEV1) and slight decreases in forced vital capacity (FVC) at HA. At both SL and
      HA, the MSV exceeded the ventilatory demands of submaximal cycle exercise that
      could be sustained for about 30 min. During progressive cycle exercise to
      exhaustion, however, peak VE was not different from MVV, either at SL or HA. We
      conclude that the small, but significant, increase in MSV with 36% O2
      administration at HA suggests that hypoxia decreases ventilatory endurance for
      flow loads as determined by the MSV. Thus, the possibility that ventilatory
      limits have a role in cessation of exercise at high altitude cannot be ruled out.

PMID- 9184734
TI  - The optokinetic cervical reflex in pilots of high-performance aircraft.
AB  - BACKGROUND: For over 60 yr, researchers and engineers have based investigations
      and the design of cockpit displays and structures upon the presupposition that
      during flight the pilot maintains a head alignment coincident with the aircraft's
      vertical axis (z-axis). Recent simulator studies have verified the existence of a
      pilot neck reflex which refutes this long-standing assumption. This reflex, named
      the opto-kinetic cervical reflex (OKCR), occurs during visual flight and is
      theorized to be an attempt by the pilot to stabilize a retinal image of the
      horizon to maintain spatial orientation. As a result, during initial banking
      maneuvers, pilots view a fixed-horizon image and not a moving-horizon. The
      research objectives were to determine if the OKCR occurs during actual flight of
      high performance jet aircraft and to model the response. HYPOTHESIS: Pilots of
      high performance aircraft will exhibit the OKCR. Additionally, the OKCR is
      dependent on the phase of banking (entering into or exiting from a banked
      position). METHODS: This was an observational study in which the head positions
      of nine pilots were recorded during actual F-15 aircraft flight and subsequently
      analyzed. RESULTS: Objective data indicate the OKCR caused pilots to tilt their
      heads during aircraft bank (p < 0.0001). Also, the reflex was found to be
      independent of the bank phase. CONCLUSION: The OKCR was shown to be a strong,
      natural response and the flight results correlated closely with simulator
      results. The effect of these results on pilot training, spatial disorientation,
      physiological injury and safety, and the redesign of displays for aircraft
      attitude and virtual reality are discussed.

PMID- 9184736
TI  - Effects of positive and negative pressure breathing on muscle sympathetic nerve
      activity in humans.
AB  - To clarify the dynamic effects of short-term continuous positive-pressure
      breathing (CPPB) and continuous negative-pressure breathing (CNPB) on sympathetic
      nerve activity, we measured muscle sympathetic nerve activity (MSNA) in the
      tibial nerve together with blood pressure, heart rate, and central venous
      pressure (CVP) during spontaneous breathing: 5, 10, and 15 mm Hg (CPPB), and -5, 
      10, and -15 mm Hg (CNPB) for 5 min, respectively, in six healthy male volunteers.
      Increasing levels of CPPB at 5, 10, and 15 mm Hg produced increasing levels of
      MSNA, however, during CNPB, MSNA was virtually constant. Mean blood pressure
      decreased and heart rate increased during CNPB, while neither factor changed
      significantly during CPPB. CVP increased during CPPB and decreased during CNPB.
      These results suggest that CPPB and CNPB do not have the inverse effects on MSNA.

PMID- 9184737
TI  - Acute mountain sickness is not altered by a high carbohydrate diet nor associated
      with elevated circulating cytokines.
AB  - We investigated whether a diet of increased carbohydrate content reduces the
      symptoms of acute mountain sickness (AMS) and whether concentrations of
      circulating cytokines rise and correlate with hypoxia and AMS. There were 19
      healthy volunteers who ingested in randomized order both a high carbohydrate (68%
      CHO) or normal carbohydrate (45% CHO) diet for 4 d. On the 4th d, subjects were
      exposed to 8 h of 10% normobaric oxygen. Each subject completed the Lake Louise
      Consensus Questionnaire (LLCQ: a questionnaire developed to quantify the common
      symptoms and consequences of AMS) at the beginning and end of each hypoxic
      session, at which times venous blood was obtained for the following cytokines:
      interleukins 1 beta, 6 and 8 (IL-1 beta, IL-6, IL-8) and tumor necrosis factor
      alpha (TNF-alpha). AMS symptoms did not differ significantly between the diets
      (LLCQ scores: 68% CHO = 10.1 +/- 3.8 vs. 45% CHO = 10.3 +/- 4.1). Cytokine
      concentrations did not change with hypoxia on either diet, nor did individual
      changes correlate with AMS symptoms. We conclude that a high carbohydrate diet
      for 4 d does not reduce the symptoms of AMS; and plasma cytokine concentrations
      do not change with hypoxia and the development of AMS and, thus, are not likely
      mediators of this syndrome.

PMID- 9184738
TI  - Anti-emetic drug effects on cognitive and psychomotor performance: granisetron
      vs. ondansetron.
AB  - The central objectives of this study were to evaluate the cognitive, psychomotor
      and subjective effects of two anti-emetic drugs of established value in the
      prophylaxis of radiation induced nausea and vomiting. The drugs of interest were
      granisetron (Kytril, SmithKline Beecham Pharmaceuticals, Philadelphia, PA; 1 mg
      tablets/2 mg dose) and ondansetron (Zofran, Glaxo Welcome, Inc., Research
      Triangle Park, NC; 8 mg tablets/8 mg dose). The experimental approach, involving
      24 active-duty military subjects, was a placebo controlled, double blind,
      crossover design with a positive control (prochlorperazine, 10 mg tablets/10 mg
      dose) condition. Testing was accomplished during the evening and early morning
      hours, between 1630 hours and 0230 hours. Therefore, fatigue stemming from an
      extended work period and a disrupted work/rest cycle was also part of the study
      design. Data were collected on the following: cognitive and psychomotor effects,
      affective state changes, temperature, serum drug levels, and side effects. The
      drugs of interest, granisetron and ondansetron, were extremely well tolerated,
      with no obvious side effects when compared to the placebo condition. Two of five
      cognitive tests detected a positive control effect and nearly all of the
      measurement instruments demonstrated a general fatigue effect, independent of the
      drug. There was no evidence of any cognitive, psychomotor or subjective state
      changes caused by either granisetron or ondansetron. It was concluded the anti
      emetic drugs, granisetron or ondansetron, would not interfere with performance
      when given prophylactically to personnel at risk of exposure to radiation.

PMID- 9184740
TI  - +GZ-induced neck injuries in Royal Australian Air Force fighter pilots.
AB  - +GZ-induced neck injuries are a relatively common occurrence in pilots of high
      performance fighter aircraft. We surveyed 52 fighter pilots from the Royal
      Australian Air Force Base at Williamtown via an anonymous questionnaire in order
      to determine the prevalence and operational significance of these injuries. The
      pilots flew either the F/A-18 Hornet or the MB326H Macchi. Of the respondents, 44
      reported having had a neck injury under +GZ. A higher rate was reported in pilots
      of the F/A-18. Most of these injuries were simple muscle sprains. There were 20
      pilots who reported their neck injury as having interfered with mission
      completion. Only 12 pilots reported doing any regular neck strengthening
      exercises, while 33 pilots reported doing preflight neck stretches immediately
      prior to high +GZ exposure. There were 14 pilots who sought medical attention for
      their injury, with 9 being taken off flight status for an average of 2 weeks. Air
      combat maneuvering sorties and the "check six" head position were identified as
      causal factors by most pilots. This study demonstrates the operational
      significance of these injuries, and highlights the need for more research into
      this important aerospace medicine issue.

PMID- 9184739
TI  - Estimation of spine forces under whole-body vibration by means of a biomechanical
      model and transfer functions.
AB  - BACKGROUND: Several investigations reveal that long-term exposure to whole-body
      vibrations can induce degenerative changes in the lumbar spine. In analogy to the
      activities of lifting or carrying loads, an assessment of the health risk should
      be possible if the forces transmitted in the spine during vibration stress are
      known. METHODS: To estimate the spine forces a biomechanical model was developed.
      In the model the human trunk, neck, and head were represented by 10 rigid bodies
      connected by visco-elastic elements. Some 56 force elements imitated the muscles
      of the body. The motion equations of the model were derived by means of the
      dynamics of systems of rigid bodies. RESULTS: The transfer functions of the model
      accelerations in x- and z-direction satisfactorily corresponded to data reported
      in the literature. Transfer functions were computed between the forces
      transmitted from the seat to the pelvis and in the lumbar spine, respectively.
      CONCLUSION: The forces between seat and pelvis were measured, then the spine
      forces were computed by means of the transfer functions. To assess the health
      risk the computed forces must be compared with the strength of the spine because
      the strength is dependent on the age and gender of the worker and decreases with
      the number of load cycles.

PMID- 9184741
TI  - Female acceleration tolerance: effects of menstrual state and physical condition.
AB  - INTRODUCTION: The literature contains a paucity of information on female
      tolerance to high sustained acceleration. With women now flying high-performance
      aircraft, gender-specific factors that may affect female acceleration tolerance
      have become increasingly important. The purpose of this investigation was to
      determine how menstrual state and physical condition affect acceleration
      tolerance. We hypothesized the menstrual cycle would have no effect on
      acceleration tolerance and that a positive correlation would exist between
      physical fitness level and tolerance to high sustained acceleration. METHODS:
      Centrifuge exposures on 8 female subjects consisted of a relaxed gradual-onset
      run (0.1 G.s-1) to the visual endpoint, a rapid-onset run (6 G.s-1) to +5 GZ for
      15 s, and a +4.5 to +7 GZ simulated aerial combat maneuver (SACM) to physical
      exhaustion. Acceleration tolerance data were collected at onset of menstruation
      and 1, 2 and 3 weeks following the onset for two complete menstrual cycles. On
      separate days, body composition, anaerobic power output and peak oxygen uptake
      were determined. Retrospective data from 10 male subjects who had performed the
      +4.5 to +7 GZ SACM were analyzed and compared to these data. RESULTS: Analysis of
      variance revealed no significant difference in relaxed tolerance or SACM duration
      between the four selected menstrual cycle time points. Time-to-fatigue on the
      +4.5 to +7 GZ SACM was positively (p < or = 0.05) correlated with absolute fat
      free mass (r = 0.87) and anaerobic power production (r = 0.76) in female
      subjects. However, when these variables were adjusted for total body mass, the
      significant correlations no longer existed. No correlation was found between SACM
      duration and absolute (L min-1) nor relative (ml.kg-1.min-1) aerobic fitness.
      Time-to-fatigue during the SACM was not significantly different between male and
      female subjects (250 +/- 97 and 246 +/- 149 s, respectively).

PMID- 9184742
TI  - Pilots' knowledge of the relationship between alcohol consumption and levels of
      blood alcohol concentration.
AB  - The U.K. Civil Aviation Authority is currently proposing that a maximum BAC
      (Blood Alcohol Concentration) limit of just 0.02% should be imposed on United
      Kingdom pilots. In this survey of 477 pilots, it was found that a large
      proportion could not determine when their BAC was likely to fall below this level
      after drinking alcohol and could, therefore, potentially inadvertently infringe
      the proposed regulation. Another large proportion of pilots felt that they were
      safe to fly before their BAC had dropped below 0.02%, which may be indicative of
      a willingness to infringe the regulations. Estimates of when it was safe to fly
      also became more inaccurate as the amount drunk increased and varied with the
      type of alcoholic beverage consumed. It was also found that the conclusions drawn
      were heavily dependent upon the formula used to estimate BAC. This methodological
      problem identified has considerable implications for the study of alcohol
      consumption when flying.

PMID- 9184743
TI  - Theoretical considerations concerning the effect of relativistic velocities on
      the rate of biological processes.
AB  - Theoretical considerations were advanced on the reaction rate of biological
      systems in a rocket accelerated at fractional levels of the velocity of light.
      The values of mass increase in reacting molecules and length contraction of space
      under these relativistic velocities attained by the hypothetical rocket were
      inserted in equations of the absolute reaction rate theory. The equations
      employed were for the frequency of collisions, and for the internal kinetic
      energy of molecular reactions. Results of both sets of equations indicated that
      reduction of reaction rates were correlated to the mass increase. This would
      imply a general slowing of all chemical, biochemical and biological processes
      taking place. A human would suffer a related decrease in metabolic rate. Contrary
      to what is generally accepted, the biological aging of the space traveler under
      velocities bearable by humans, namely under 0.50c, would follow a pace very
      similar to that of an observer remaining in the resting frame of reference. With
      increased increments of the velocity, the space traveler would display a more
      intense lowering of the metabolic rate, with signs and symptoms comparable to
      body core hypothermia. Metabolic rates at insufficient levels to maintain the
      vital functions would be attained at 0.70c and higher, leading swiftly to coma
      and death. The presence of an endocrine dysfunction such as hypothyroidism or
      obesity in the space traveler would aggravate the signs and symptoms. Space
      travel at efficient velocities would be unbearable for a warm-blooded animal.

PMID- 9184744
TI  - Forum for leadership in preventive medicine: impact on the specialty of aerospace
      medicine.
AB  - BACKGROUND: The American College of Preventive Medicine (ACPM) has just
      published. The Specialty of Preventive Medicine: Leadership in Medicine for the
      21st Century (Forum Report). The Forum Report summarizes a 3-yr effort by leaders
      of the ACPM, American Board of Preventive Medicine (ABPM), professional
      organizations, residency training programs, and residents-in-training to examine
      the critical issues facing the specialty of Preventive Medicine (PM) and to
      develop a vision and strategies for the future. The Forum Report could have
      profound repercussions on the specialty of Aerospace Medicine (ASM). METHODS: The
      author reviewed the history behind the development of the Forum Report and
      assessed the Report's recommendations with respect to their possible
      ramifications on the specialty of ASM. RESULTS: The Forum Report includes 34
      recommendations to enhance the specialty of PM. Of most interest to the ASM
      community is the Forum's conclusion that the most critical issue facing PM is
      unification of the specialty. It recommends, therefore, that the ABPM establish
      PM certification for all individuals at the end of the practicum year, with area
      certification [Occupational Medicine (OM), General Preventive Medicine/Public
      Health (GPM/PH), and ASM) occurring only after more specialized training and
      practice. DISCUSSION: The ASM community needs to be aware of the Forum Report's
      recommendations and enter the debate on the viability of the specialty of ASM.
      The Aerospace Medical Association should take the lead in this effort.

PMID- 9184745
TI  - Investigations of immune parameters in a cosmonaut after a long-duration flight.

PMID- 9184746
TI  - Physical property analysis and bacterial adhesion on a series of phosphonated
      polyurethanes.
AB  - Glycerophosphorylcholine (GPC) was incorporated as the chain extender in a series
      of poly(tetramethylene oxide)-based polyurethane block copolymers. In order to
      determine the feasibility of use of these polyurethanes in biomedical devices,
      the effects of GPC incorporation on physical properties were studied. The effect
      of soft-segment molecular weight was also investigated. Biocompatibility of these
      materials was studied with regard to bacterial adhesion and protein deposition.
      Tensile testing showed that as GPC content increased, elongation at break
      decreased, while Young's modulus increased. Differential scanning calorimetry
      (DSC) results showed slightly decreased glass transition temperatures (Tgs) with
      increasing GPC content, indicating increased phase separation. Dynamic mechanical
      analysis (DMA) confirmed the decrease in Tg and the increase in rubbery plateau
      modulus with increasing GPC content. Water absorption was also increased with GPC
      content. Decreased bacterial adhesion was found on the GPC-containing materials
      compared to other functionalized polyurethanes. These experiments were carried
      out in a radial flow chamber utilizing automated video microscopy. Bacterial
      attachment was found to be lower on the GPC-containing polyurethanes both in the
      absence of and after pre-adsorption with plasma proteins.

PMID- 9184747
TI  - Controlled release of antibiotics from biomedical polyurethanes: morphological
      and structural features.
AB  - Polymer-associated infections are of increasing importance. Antistaphylococcal
      antimicrobial substances (ciprofloxacin, gentamycin, fosfomycin, flucloxacillin)
      were incorporated into polyurethanes by the solvent casting technique. Drug
      release rates, bacterial colonization and morphological features were evaluated
      to predict and understand the antimicrobial activity of these delivery systems.
      Drug release characteristics were investigated by standard bioassay and high
      performance liquid chromatography (HPLC), and the physico-chemical mechanisms of
      the delivery were discussed. Ciprofloxacin hydrochloride showed a fast initial
      release rate, whereas gentamicin-base was characterized by a more continuous
      release type of behaviour. Bacterial colonization to the antibiotic-loaded
      polyurethanes was inhibited effectively by preparations showing a slower but more
      sustained antimicrobial delivery. Polyurethane-antibiotic combinations were most
      homogeneous for gentamicin-base and flucloxacillin as shown by scanning electron
      microscopy (SEM). In polymers loaded with fosfomycin and ciprofloxacin a granular
      structure of the crystallized drug embedded in the polyurethane matrix could be
      demonstrated. Physico-chemical similarity of the polymeric material and the
      antibiotics is important for the homogeneity of polymer-antibiotic combinations.
      High homogeneity is required for a sustained and prolonged release over time and
      effective inhibition of bacterial colonization.

PMID- 9184748
TI  - Heparinization of gas plasma-modified polystyrene surfaces and the interactions
      of these surfaces with proteins studied with surface plasmon resonance.
AB  - Polystyrene surfaces obtained by spin-coating a solution of polystyrene in
      toluene on a gold layer were functionalized with carboxylic acid groups by
      preadsorption of the sodium salt of undecylenic acid, followed by an argon plasma
      treatment. A conjugate of albumin and heparin (alb-hep) was covalently
      immobilized onto the functionalized surface via preactivation of carboxylic acid
      groups with a water-soluble carbodiimide. The immobilization of alb-hep conjugate
      and the subsequent interactions of the heparinized surface with antithrombin III
      (ATIII, a heparin cofactor) and thrombin were monitored with surface plasmon
      resonance (SPR). The surface concentration of conjugate as determined with SPR
      deviated quantitatively from the results obtained with radiolabelled conjugate.
      The difference in surface concentrations of conjugate obtained with the two
      methods probably originates from the uncertainty of the refractive index of the
      alb-hep conjugate in the SPR technique. ATIII could be bound to the surface
      modified with alb-hep conjugate but not to a polystyrene surface modified with
      albumin. Rabbit anti-human ATIII did bind to the alb-hep surface previously
      exposed to ATIII, confirming the presence of surface bound ATIII. The alb-hep
      immobilized surface was able to bind much more thrombin than ATIII, which is
      probably due to the less specific heparin-thrombin interaction as compared to the
      heparin-ATIII interaction. This study shows that SPR is a technique that can be
      used to study, in real time, both the modification of polymer surfaces and the
      subsequent interactions of the modified surfaces with proteins.

PMID- 9184749
TI  - In vitro release kinetics of biologically active transforming growth factor-beta
      1 from a novel porous glass carrier.
AB  - Sol-gel silica-based porous glass (xerogel) was used as a novel carrier material
      for recombinant human transforming growth factor-beta 1 (TGF-beta 1). Room
      temperature synthesis procedures included sol preparation, the addition of TGF
      beta 1 solution to the sol, subsequent gelation and drying. After determination
      of optimal synthesis parameters, the material was assayed in vitro for its
      ability to release biologically active TGF-beta 1 in a controlled manner.
      Sustained release of TGF-beta 1 over a 7-day period was demonstrated. On the
      basis of published TGF-beta 1 potency, the amount released is capable of
      eliciting bone tissue reactivity. These findings suggest that this novel glass
      growth factor composite may serve as an effective bone graft material for the
      repair of osseous defects.

PMID- 9184750
TI  - In vitro degradation of pH-sensitive hydrogels containing aromatic azo bonds.
AB  - Biodegradable and pH-sensitive hydrogels containing azoaromatic moieties were
      synthesized from the same polymeric precursors by two synthetic methods, namely a
      polymer-polymer reaction and cross-linking of polymeric precursors. The effect of
      the synthetic route employed and the detailed network structure on in vitro
      degradation of hydrogels was studied. Regardless of the synthetic method used,
      two patterns of degradation were observed. Hydrogels with lower cross-linking
      density underwent a surface erosion process and degraded at a faster rate.
      Hydrogels with higher cross-linking densities degraded at a slower rate by a
      process where a colourless degradation front moved inward to the yellow core. It
      appears that hydrogels synthesized by a polymer-polymer reaction degraded at a
      slightly faster rate than their analogues synthesized by cross-linking of
      polymeric precursors. The degradation rate of a hydrogel was compared with those
      of a linear azopolymer and a low-molecular-weight azosubstrate (methyl orange)
      respectively. The degradation rates were in the order of hydrogel < linear
      azopolymer < low-molecular-weight azosubstrate.

PMID- 9184751
TI  - Wear characteristics of ceramic-on-ceramic for hip endoprostheses.
AB  - Femoral ball heads of aluminium oxide or zirconium oxide ceramics are used for
      total hip replacement. This application is based on their attractive tribological
      properties. Standard and state-of-the-art are femoral ball heads made of alumina
      (Al2O3) articulating against acetabular cups of polyethylene (PE-UHMW) and
      zirconia (Y-TZP) heads articulating against polyethylene cups. A very attractive
      wear couple is ceramic-on-ceramic. Some of the various ceramic combinations have
      been tested using the ring-on-disc method according to ISO 6474. The combination
      alumina/alumina was found to produce extremely low wear; catastrophic wear was
      found for the combinations alumina/Y-TZP and Y-TZP/Y-TZP.

PMID- 9184752
TI  - Mechanical model for critical strain in mineralizing biological tissues:
      application to bone formation in biomaterials.
AB  - A simple theoretical model for the role of strain energy density in the initial
      mineralization of soft tissues is presented and used to derive a limit of the
      allowable strain in tissue engineered biomaterials. The model incorporates the
      mechanical energy in calcified tissue due to time-varying loads into the more
      commonly used energetic arguments for mineralization. By using the Voight (equal
      strain) and Reuss (equal-stress) composite material models to relate the
      volumetric density of calcified tissue to overall material modules, two models
      were developed to assess the effect of an imposed overall material strain on
      mineralization. A rate equation based on strain energy was used to model the
      kinetics of mineralization, and the stability of the rate equation was assessed,
      leading to a limit on overall material strain based on the specific energy for
      mineralization of soft tissues. The result depended on the stiffness of the
      material in series with the mineralizing tissue. Taking the stiffness of the
      material in series with the tissue as infinite lead to a prediction of critical
      strain for mineralization in the calcifying biological tissue which was the same
      on the Reuss and Voight models. The interaction of this theoretical model with
      biological factors and some clinical implications of the model are discussed.

PMID- 9184754
TI  - Emerging concepts of self-organization and the living state. Introduction.

PMID- 9184753
TI  - Covalent bonding of heparin to a vinyl copolymer for biomedical applications.
AB  - In order to prepare polymer surfaces of vinyl type, provided with long-term
      haemocompatibility, a commercial ethylene-vinyl alcohol copolymer (EVAL) was
      covalently heparinized, employing two different bifunctional reagents (adipoil
      chloride and hexamethylene diisocyanate). The amount and activity of the heparin
      bonded to the polymer films were evaluated as a function of the concentration of
      the heparin solutions employed. Also, the influence exerted by the presence of
      various hydrophilic 'spacing arms' of different molecular weights, either neutral
      or provided with electrical charge, was investigated. By in vitro measurements of
      activated partial thromboplastin time it was seen that all the heparinized
      samples possessed a high degree of haemocompatibility. For the sake of
      comparison, heparin was also bonded ionically to EVAL functionalized by
      introduction of quaternary ammonium groups bonded covalently (by adipoil
      chloride) to the hydroxyl groups of the polymer. It was seen that the covalent
      immobilization system provides the polymer surfaces with a superior
      haemocompatibility.

PMID- 9184755
TI  - A criterion of relative degree of chaos or order for open systems.
AB  - The main concepts of the new interdisciplinary branch of science known as
      'physics of open systems' are discussed and a possible criterion of relative
      degree of order in nonequilibrium states of open systems is especially
      considered. On that basis the concept of 'norms of chaos' (or 'norms of order')
      is set forth and the definition of processes of degradation and self-organization
      is given a physical meaning. Some cases in which use can be made of the methods
      of physics of open systems even in economics, sociology and physiology are
      briefly discussed.

PMID- 9184756
TI  - Origin of biochemical organization.
AB  - The problems of the origin of life and biochemical evolution are analyzed in the
      context of the biochemical organization concept proposed earlier by the authors.
      The traditional view according to which the evolution of biological systems
      occurred from lower levels to systems of higher levels is criticized. It is
      suggested that the formation of the cell and biological systems of lower levels
      (subcellular structures, supramolecular structures, biomacromolecules) occurred
      in a coordinated manner. The liposome and inorganic hypotheses of the origin of
      life are discussed. Regosome model based on ideas of Nussinov and Mekler which
      combines advantages of the liposome and inorganic hypotheses has been adopted and
      modernized. It is suggested that the initial metabolism of protocells based
      itself on C2-C3-compounds. Autodevelopment of catalytic systems of protocells is
      discussed.

PMID- 9184757
TI  - The emergence of the non-cellular phase of life on the fine-grained clayish
      particles of the early Earth's regolith.
AB  - A scenario of the origin of the very first ribonucleoproteinoid virus-like
      complexes, which is based on their synthesis in the interlaminar spaces of
      clayish grain regolith of the primitive Earth, about 4 billion years ago when
      water in the form of liquid drops first appeared. The proposed model explains the
      origin of chirality of modern biopolymers as a result of preferential adsorption
      of biomonomers on such grains.

PMID- 9184758
TI  - Biodynamics for the emergence of energy consumers.
AB  - What is unique to biodynamics in vivo or dynamics leading to the emergence of
      biological organizations is a frozen aggregate of degrees of freedom in motion
      that can change its constituent members in time. Association and dissociation of
      degrees of freedom in the frozen aggregate is information-generative, in the
      sense that their realization proceeds in a contingent manner, with no unique
      pattern being predetermined. In particular, dissociation of some of the degrees
      of freedom from the parental aggregate becomes information-generative when the
      dissociative interaction initiated by thermal agitation originating in the
      ambient takes significantly longer time than the interval of the inverse thermal
      frequency. For instance, ATP hydrolysis with the help of myosin following the
      preceding association of an ATP molecule with the myosin happens to be a case of
      such a dissociative interaction, in which the duration of the interaction is far
      greater than the inverse of thermal frequency. One dominant mode of biodynamics
      in vivo is to effectively materialize a heat engine by preparing a local region
      with a temperature lower than that of the surroundings, thereby letting the
      duration time of the dissociative interaction be far greater than the inverse of
      thermal frequency. Evolutionary emergence of most primitive biological
      organizations would coincide with a de novo appearance of a heat engine that
      could hold thermal agitations from the surroundings locally there and could act
      upon the latter accordingly.

PMID- 9184759
TI  - Molecular semantics and the origin of life.
AB  - The physical origin of life addresses itself to a semantic process on material
      grounds, in which causation toward contextualization is at work. Physically
      semantic process of whatever kind is specific in that every material participant
      is searching and modifying the material context to be fitted in. Fundamental to
      the physical semantics is the process of measurement proceeding internally among
      the constituent material participants, whereas the molecular syntax alone as
      embodied in the form of the quantum-mechanical equation of motion supplemented
      independently by exogenous boundary conditions cannot cope with the material
      process underlying the origin. A basic physical attribute of the phenomenon
      called life is variable duration, in contrast to invariant duration of Galilean
      inertia. In fact, moleculars replication thought as a harbinger of the phenomenon
      of life is a concrete form of variable duration and could be established unless
      internal measurement being instrumental to physically semantic process is
      forcibly eliminated by some external means. Physical experiments on the onset of
      molecular replication could become feasible only when external controllability
      over the intended experiments even at nano-meter scales is abandoned so as to
      save the room of internal measurement on the part of participating molecules.

PMID- 9184760
TI  - Determination of the relative degree of order in a chain of diffusion-linked self
      oscillators simulating peristalsis of thin tubules according to the S-theorem
      criterion.
AB  - The criterion of the relative degree of order (RDO) on the basis of the S-theorem
      for a non-equilibrium system is applied to the analysis of the state of a chain
      of diffusion-linked self-oscillators, a system which models the peristalsis of
      thin tubules, e.g. in a biological tissue, as well as a number of physicochemical
      systems. It is shown that the calculation of the RDO and of the effects of
      various actions on a non-equilibrium system can be carried out efficiently
      without any knowledge of the details of the local kinetics of the diffusion-link
      chain, said calculation being exploited for evaluating such effects just on the
      basis of experimental data.

PMID- 9184761
TI  - Self-organization in semiconductor physics.
AB  - Non-equilibrium dissipative systems from semiconductor physics have prevailed as
      a paradigmatic testing field for complex non-linear dynamics during the last
      decade. Especially, low-temperature impact ionization breakdown in extrinsic
      germanium crystals displays a variety of interesting nonlinear phenomena, such as
      spontaneous oscillations and filamentary patterns of the current flow. We report
      on recent experimental results concerning the interplay between spatial and
      temporal degrees of freedom during the onset of semiconductor breakdown.
      Quantitative evaluation of characteristic scaling properties supports the
      applicability of the model of self-organized criticality.

PMID- 9184762
TI  - The enigma of microtubules and their self-organizing behavior in the
      cytoskeleton.
AB  - The cytoskeleton of eukaryotic cells contains networks of protein polymers called
      microtubules which structurally and functionally organize their interiors. Both
      in vivo and in vitro microtubules exhibit a fascinating and yet poorly understood
      array of important functions involving complex self-organization phenomena which
      are very sensitive to physiological and laboratory conditions, respectively. In
      this paper we discuss the main physical characteristics of microtubules focusing
      our attention on four particular aspects: (a) the dynamics of their assembly and
      disassembly processes (b) the types and the range of existence of ordered dipolar
      phases and (c) modes of energy transfer and (d) information processing
      capabilities.

PMID- 9184763
TI  - Origin of life and the underlying physics of the universe.
AB  - The thesis is put forward that the non-linear self-organizing dynamics of
      biological systems are inherent in any physical theory that satisfies the
      requirements of both quantum mechanics and general relativity. Biological life is
      viewed as an extension of these underlying dynamics rather than as an emergent
      property of systems that reached a requisite threshold of complexity at a
      definite point in time. The underlying dynamics are based on interactions between
      manifest material organizations and an unmanifest vacuum sea whose density
      structure is isomorphic to the metric structure of space-time. These interactions
      possess an intrinsic self-corrective character, due to the fact that quantum
      processes lead to changes in particle states that have a random aspect, while
      general relativity requires that the distribution of manifest and unmanifest
      particles be self-consistent. The model implies vacuum hysteretic effects that
      would bear on nanobiological phenomena and that might be detected through
      nanobiological techniques.

PMID- 9184764
TI  - The topology of perceptive functions as a corollary of the theorem of existence
      in closed spaces.
AB  - The capability for a system of perceiving both outer objects and an inner self
      are two fundamental features of abstract mathematical objects endowed with the
      properties of topologically closed sets. Such structures exist upon intersection
      of topological spaces owning different dimensions. Then, the theorem of Jordan
      Veblen provides their capability of being observable, while the theorems of
      Brouwer and of Banach-Caccioppoli provide two kinds of fixed points which account
      for the properties of so-called right and left brain functions. Fixed points
      account for the biological 'self', and the system provides theoretical
      justification for the existence of brain structure/function relationships,
      including memory, emotion, and respective characteristics of right and left
      hemispheres. Hence, an abstract topological reasoning based on set properties,
      provides evidence that the observer's function directly infers from the
      phenomenon of existence and that it belongs to the same mathematical system as
      the property of being observable. Order relations are raised from equivalence
      relations by Poincare groups, upon mappings on the sets of functions and related
      homotopic transformations in sequences of intersections. Therefore, time is a
      construction of abstract brain functions, and a living organism just fills the
      system with appropriate molecular structures.

PMID- 9184765
TI  - Some remarks on the experimental realization of a mind machine.
AB  - The brain not only makes use of measuring apparatuses, but perhaps has the
      potential to serve as one itself. Since Einstein-Podolsky-Rosen correlations must
      be absent between observer and object in order for a quantum state to become
      reducible, it is tempting to perturb measurements by changing the quantum state
      of the brain. The latter would then be part of the measurement. What kind of
      effects would one expect? It appears that a new psychophysical problem has been
      opened up, since any observable consequences would be confined to the
      subjectivity of the observer.

PMID- 9184771
TI  - Cancer and infection: estimates of the attributable fraction in 1990.
AB  - Various estimates of the proportion of all cancers attributable to infections
      have been proposed but none have been numerically justified. We have reviewed the
      evidence for "causality" with respect to infectious agents linked with cancer and
      estimated the fraction of all cancer cases concerned that are attributable to it.
      The etiological fraction was applied to the estimated annual incidence of cancer
      at each specific site in 1990, and the number of attributable cases was obtained.
      We estimate that 15.6% (1,450,000 cases) of the worldwide incidence of cancer in
      1990 can be attributed to infection with either the hepatitis B and C viruses,
      the human papillomaviruses, EBV, human T-cell lymphotrophic virus I, HIV, the
      bacterium Helicobacter pylori, schistosomes, or liver flukes. There would be 21%
      fewer cases of cancer in developing countries (1,000,000 fewer cases per year)
      and 9% fewer cases in developed countries (375,000 fewer cases per year) if these
      infectious diseases were prevented. The attributable fraction at the specific
      sites varies from 89% of cervix cancers attributable to the papillomaviruses to
      1% of all leukemias attributable to human T-cell lymphotrophic virus I.

PMID- 9184772
TI  - Association of family history of cervical, ovarian, and uterine cancer with
      histological categories of lung cancer: the Iowa Women's Health Study.
AB  - A family history of cervical, ovarian, or uterine cancer has been shown to be
      associated with increased lung cancer risk among postmenopausal women. The
      present report examines the hypotheses that a family history of cervical cancer
      is positively associated with histological subtypes of lung cancer most strongly
      associated with smoking and that a family history of ovarian or uterine cancer
      are positively associated with risk of adenocarcinoma of the lung. Data are from
      the Iowa Women's Health Study, a prospective cohort study of 34,480 women ages 55
      69 in 1986. Personal smoking histories, use of alcohol, and family history of
      selected cancers in first- and second-degree relatives were collected at
      baseline. Follow-up for cancer occurrence was achieved through the State Health
      Registry of Iowa. After baseline exclusions, a total of 343 incident lung cancers
      were identified in the cohort at risk through 1994. Women with a family history
      of cervical cancer in a first-degree relative had a multivariate-adjusted
      relative risk of lung cancer of 1.6 [95% confidence interval (CI): 0.98-2.6]
      compared to women without a family history. The risk was particularly high for
      malignancies most strongly associated with smoking (squamous, small cell, and
      large cell tumors; relative risk, 2.0; 95% CI, 1.1-3.7). Consistent with our
      hypotheses, a family history of ovarian cancer was associated with an
      approximately 2-fold increased risk (multivariate adjusted) of adenocarcinoma of
      the lung; the association with malignancies more strongly associated with smoking
      was inverse (relative risk, 0.6; 95% CI, 0.2-2.4). A family history of uterine
      cancer was not associated with adenocarcinoma, but there was a positive
      association observed for the most strongly smoking-associated histological types.
      These results suggest that a family history of cervical cancer is a modest
      independent risk factor for lung cancers most strongly associated with smoking,
      and a family history of ovarian cancer is a risk factor for adenocarcinoma of the
      lung.

PMID- 9184773
TI  - Serum micronutrients and upper aerodigestive tract cancer.
AB  - Numerous dietary studies have found that vegetables and fruits protect against
      upper aerodigestive tract cancer. To evaluate the role of beta-carotene and other
      specific carotenoids, a nested case-control study using prediagnostic serum was
      conducted among 6832 American men of Japanese ancestry examined from 1971 to
      1975. During a surveillance period of 20 years, the study identified 28
      esophageal, 23 laryngeal, and 16 oral-pharyngeal cancer cases in this cohort. The
      69 cases were matched to 138 controls. A liquid chromatography technique,
      designed to optimize recovery and separation of the individual carotenoids, was
      used to measure serum levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene,
      alpha-carotene, beta-carotene, retinol, retinyl palmitate, and alpha-, delta-,
      and gamma-tocopherol. With adjustment for cigarette smoking and alcohol intake,
      we found that alpha-carotene, beta-carotene, beta-cryptoxanthin, total
      carotenoids and gamma-tocopherol levels were significantly lower in the 69 upper
      aerodigestive tract cancer patients than in their controls. Trends in risk by
      tertile of serum level were significant for these five micronutrients. These
      significant trends persisted in cases diagnosed 10 or more years after phlebotomy
      for the three individual carotenoids and total carotenoid measurements. The odds
      ratios for the highest tertile were 0.19 (95% confidence interval, 0.05-0.75) for
      alpha-carotene, 0.10 (0.02-0.46) for beta-carotene, 0.25 (0.06-1.04) for beta
      cryptoxanthin, and 0.22 (0.05-0.88) for total carotenoids. When the cases were
      separated into esophageal, laryngeal, and oral-pharyngeal cancer, both alpha
      carotene and beta-carotene were consistently and strongly associated with reduced
      risk at each site. The findings suggest that alpha-carotene and other
      carotenoids, as well as beta-carotene, may be involved in the etiology of upper
      aerodigestive tract cancer.

PMID- 9184774
TI  - Telomerase activity in premalignant and malignant lesions of human oral mucosa.
AB  - Recent studies have demonstrated a strong association between carcinogenesis and
      re-activation of telomerase in various human tumors. In the present study, we
      have analyzed the telomerase activity in 105 oral mucosal samples, including
      normal mucosa and premalignant and malignant lesions, by using the telomeric
      repeat amplification protocol assay. The telomerase activity was detected in
      normal oral squamous epithelium and in 75% of the oral leukoplakias and oral
      carcinomas. Although the telomerase activity was observed in normal and
      hyperplastic squamous epithelium, it showed some relationship with certain
      clinico-pathological factors in malignant lesions. Telomerase activity was found
      to have a relationship with the grade of tumor differentiation. Of 34 well
      differentiated squamous cell carcinomas, only 10 (30%) exhibited high telomerase
      activity, whereas in moderately or poorly differentiated squamous cell
      carcinomas, all seven (100%) tumors displayed high activity. In addition, the
      level of telomerase activity had an inverse correlation with the treatment
      response in the early-stage tumors, and the activity differed significantly
      between the tumors in the following intraoral sites: nonkeratinizing mucosa
      (buccal mucosa, alveolus, and floor of mouth) and tongue. This preliminary result
      shows that telomerase activity is present in normal oral squamous epithelium, as
      it is in normal hematopoietic cells and in carcinomas, and that telomerase
      activity has a relationship with degree of tumor differentiation and treatment
      response. Thus, assessing the telomerase activity may be a useful prognostic
      marker in oral squamous cell carcinomas.

PMID- 9184776
TI  - Assay reproducibility of hormone measurements in postmenopausal women.
AB  - As part of a breast cancer case-control study of serum hormones conducted in
      Columbia, MO, we included several replicate quality control samples to monitor
      the consistency of laboratory assays. Sera were obtained from three
      postmenopausal women; from each woman, three samples were placed randomly in each
      of nine batches with the laboratory unaware of which sample corresponded to whom.
      Laboratory assays for estrone (E1), estradiol (E2), testosterone, androstenedione
      (Adione), E1SO4, dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating
      hormone (FSH), sex hormone binding globulin (SHBG), and percentages of free and
      albumin-bound E2 were done at a single academic facility. ANOVA results showed
      that hormone values varied considerably from one batch to the next. The overall
      coefficients of variation (CVs) estimated for E2, percentage of unbound E2, and
      percentage of albumin-bound E2 were higher than 15%, but of these, only
      percentage of unbound E2 had both inter- and intra-assay CVs greater than 10%.
      Intraclass correlations (ICC) for FSH, SHBG, and DHEAS were high, suggesting that
      these assays are suitable for population-based studies attempting to link hormone
      levels to disease risk. The ICC estimated for E1SO4 was quite low due to aberrant
      values reported in a single batch. For the remaining hormones, the ICCs were fair
      (ranging from 47% for albumin-bound E2 to 67% for Adione), and studies using
      these assays would require a substantial increase in the sample size to detect
      small case-control differences.

PMID- 9184775
TI  - Mitogenic growth factors in breast fluid obtained from healthy women: evaluation
      of biological and extraneous sources of variability.
AB  - Peptide growth factors (GFs), including epidermal GF (EGF) and transforming GF
      alpha (TGF-alpha), are presumed to play an important role in the local regulation
      of breast cell proliferation. Breast fluid collected by nipple aspiration
      provides a potential means to assess the concentration of these factors in
      contact with the ductal epithelium. Although identification of immunoreactive EGF
      like GFs in breast fluid has been reported previously, we performed this study to
      evaluate the sensitivity and reliability of newer RIA methods and to characterize
      the sources and amounts of both intra- and intersubject variability. We also
      evaluated the relationship of breast fluid EGF and TGF-alpha levels to each other
      and to plasma levels of estradiol and progesterone. Breast fluid and plasma
      samples were obtained two to four times at weekly intervals from 18 healthy,
      premenopausal women. EGF and TGF-alpha were measured by competitive binding RIA.
      Both GFs were detected with good precision in all breast fluid samples analyzed,
      using dilutions as low as 1:100 for EGF (1 microliter) and 1:25 for TGF-alpha (4
      microliters). The correlations between the right and left breasts, sampled
      concurrently, were r = 0.78 (P = 0.003) for EGF and r = 0.89 (P = 0.0001) for TGF
      alpha. For both GFs, the variation between women was substantially greater than
      the variation between breasts or over time in an individual woman, particularly
      for EGF, for which there were 100-fold differences between women in mean levels.
      When samples from multiple women were analyzed together, we found no apparent
      relationships between EGF and TGF-alpha levels or between either GF level and
      menstrual cycle phase or plasma hormone concentrations. However, in random
      effects analyses, EGF levels within an individual were significantly associated
      overall with both TGF-alpha (P = 0.02) and plasma estradiol levels (P = 0.01).
      These data, which are the first comprehensive results on the feasibility of
      measuring mitogenic GFs in breast fluid, support the conclusion that women
      secrete consistent and individually distinct levels of EGF and TGF-alpha and
      that, in at least some women, EGF secretion in vivo covaries with both TGF-alpha
      in breast fluid and circulating estradiol.

PMID- 9184777
TI  - Quantitative detection of ultraviolet-specific p53 mutations in normal skin from
      Japanese patients.
AB  - We have previously developed sensitive methods to detect UV-specific p53
      mutations (CC to TT tandem mutations) and have reported that such mutations could
      be found in the normal skin cell populations of sun-exposed body sites, but not
      in those of covered sites, in Australian cancer patients. We have now further
      refined our allele-specific PCR method for detecting CC to TT mutations at codons
      247/248 of the p53 gene to allow quantitative measurements. Using DNA containing
      this mutation from a tumor as a standard for calibration and 5 micrograms of
      genomic DNA/PCR reaction, we could detect 1 mutant allele in about 10(6) wild
      type alleles. It is essential to use purified primers and 64 degrees C as the
      annealing temperature for PCR. Our method has been applied in a study of the
      correlation of sun exposure and accumulation of CC to TT mutations in normal skin
      biopsies from Japanese patients. There were more p53 mutations in samples taken
      from sites that were chronically exposed to the sun than in those from covered
      sites. A significant trend of increased p53 mutation frequency with increase in
      age of subjects was found, suggesting the cumulative nature of the mutation. On
      the other hand, the p53 mutation frequency was higher in patients with
      premalignant tumors or nonmelanocytic skin cancer than in patients with only
      benign tumors. These results confirm the utility of PCR-based p53 gene mutation
      assays for the measurement of exposure to UV as well as for predicting the risk
      of UV-associated skin cancer.

PMID- 9184778
TI  - Development of a urinary riboflavin adherence marker for a wheat bran fiber
      community intervention trial.
AB  - Development of a reliable marker of adherence to high-fiber diets is essential
      for accurately assessing dietary fiber intake in community interventions and
      clinical trials. The objective of this study was to evaluate the feasibility of
      using a riboflavin tracer incorporated into wheat bran cereal to determine fiber
      intake and compare results to the more traditional methodology of measuring stool
      weight. The inpatient phase of the study established that the excretion of
      urinary riboflavin was highly correlated with the dose of the riboflavin-spiked
      wheat bran cereal (r = 0.95, P < 0.005) and could be used as a biomarker to
      validate fiber supplement intake. The outpatient clinical intervention included a
      group of seven African-American men and women, who were asked to incorporate 1/2
      cup of wheat bran cereal (11.6 g of dietary fiber) into their daily diet for a 6
      week period. The cereal was spiked with a 28-mg dose of riboflavin. Baseline
      measurements of urinary riboflavin and stool weight were compared to
      postintervention levels. Comparison of pre- and postintervention measures of
      riboflavin excretion showed a significant increase (0.8 +/- 0.1 versus 6.0 +/-
      0.6 mg/day, P < 0.02), which confirmed a high level of adherence to the dietary
      intervention. Although wet stool weights at baseline were significantly lower
      than postintervention (106 +/- 20 versus 146 +/- 23 g/day; P < 0.03), differences
      in dry stool weights did not reach significant levels (28 +/- 4 versus 33 +/- 5
      g/day, P < 0.30). Furthermore, pre- and poststool measurements overlapped and
      could not provide definitive data on participant adherence. These results
      indicate that the riboflavin tracer was a more sensitive biomarker of wheat bran
      fiber supplementation than stool weight and provided an accurate method for
      validating adherence to the dietary intervention. A riboflavin marker provides a
      valid technique for adherence assessment in large-scale community trials, in
      which collection of 3-day fecal samples is not a manageable option.

PMID- 9184779
TI  - CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells
      detected using the polymerase chain reaction: a new prostate cancer biomarker.
AB  - Cancer-associated somatic genome alterations offer great promise as cancer
      biomarkers. Here we describe a new biomarker for human prostate cancer: extensive
      methylation of deoxycytidine nucleotides distributed throughout a 5' "CG island"
      region of the pi-class glutathione S-transferase gene (GSTP1). Using the PCR to
      amplify a GSTP1 promoter sequence fragment containing 12 recognition sites for
      HpaII and MspI, 52 of 57 (91%) prostatic carcinoma DNA specimens demonstrated
      extensive somatic increases in deoxycytidine methylation, detected as
      amplification of target GSTP1 promoter sequences following HpaII digestion, but
      not following MspI treatment. Using nested primer sets, a sensitive PCR assay for
      extensive GSTP1 CG island methylation changes was developed that was capable of
      detecting 200 pg of prostate cancer cell DNA among 1 microgram of normal
      leukocyte DNA. This GSTP1 CG island DNA methylation assay, which targets a
      somatic genome change present in most prostate cancer cells but not in normal
      cells, may serve as a new molecular diagnosis and staging tool to aid in prostate
      cancer detection and treatment.

PMID- 9184780
TI  - Why do women's attitudes toward mammography change over time? Implications for
      physician-patient communication.
AB  - The present study examines women's decision making about mammography over a 1
      year period, using "decisional balance," a summary of women's positive and
      negative perceptions about mammography derived from the Transtheoretical Model
      (TTM). Data were from a survey of women ages 50-74 years who completed both the
      baseline and 1-year follow-up telephone surveys (n = 1144) for an intervention
      study to increase the use of mammography screening. A shift toward less favorable
      perceptions about mammography was related to being a smoker and not having a
      recent clinical breast examination and Pap test. Change in women's attitudes
      toward mammography was also related to four dimensions of a woman's information
      environment. Women who rated the opinions of a physician as somewhat or not
      important, those who reported that at least one family member or friend
      discouraged them from having a mammogram, and women who felt they lacked enough
      people in their social network with whom they could discuss health concerns were
      less likely to express favorable attitudes about mammography over 1 year. In
      contrast, women who consistently communicated the value of mammography to others
      expressed more favorable views of screening over the study period. Interventions
      designed to promote breast cancer screening must recognize that a woman not only
      reacts to mammography information provided by significant others in her social
      network but may proactively reach out to others as an advocate of breast cancer
      screening, thus reinforcing or changing others' opinions or behavior as well as
      her own.

PMID- 9184781
TI  - Feasibility of using volunteer research staff to deliver and evaluate a low-fat
      dietary intervention: the American Cancer Society Breast Cancer Dietary
      Intervention Project.
AB  - This report presents the results of a study to examine the feasibility of using
      volunteers as research staff for a randomized trial of whether reduction in
      dietary fat intake could prevent or delay breast cancer recurrence. We examined
      whether volunteers could be trained to recruit study participants, deliver a
      complex and intensive dietary intervention, and monitor intervention
      effectiveness. Volunteers, who were mostly employed nurses and dietitians,
      screened 521 women, of whom 293 were eligible and 144 were randomized.
      Participants were postmenopausal women under age 75, who had recently been
      diagnosed with breast cancer and treated with either mastectomy or lumpectomy. At
      1 year postrandomization, 77% of intervention and 75% of control participants
      remained active in the study. Intervention effects (change in intervention group
      minus change in control group) at 3, 6, and 12 months postrandomization were 5.9,
      8.4, and 7.2% energy from fat and 1.7, 3.0, and 3.5 kg body weight (all P <
      0.001). These results were similar to those from other studies that used paid,
      professional staff to deliver and monitor interventions. Results from this
      feasibility study suggest that volunteer-based health organizations can provide
      research opportunities for health practitioners and can conduct high-quality
      research at lower costs.

PMID- 9184782
TI  - Folic acid supplementation and cell kinetics of rectal mucosa in patients with
      ulcerative colitis.
AB  - It has been suggested that colon cancer risk in ulcerative colitis (UC) is
      correlated to a reduced bioavailability of folate. We studied the effects of
      folate supplementation on the pattern of rectal cell proliferation in patients
      affected by long-standing UC. In the rectal mucosa of these patients, an
      expansion of proliferating cells to the crypt surface is found frequently. This
      abnormality is considered an intermediate biomarker in chemoprevention trials.
      Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with
      UC in remission for 1 month at least were assigned randomly to one of the
      following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell
      proliferation was analyzed through immunohistochemistry on sections of rectal
      biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine.
      Fragments were taken at admission to the study and after 3 months of treatment.
      As compared to the baseline values, after 3 months of therapy in patients treated
      with folinic acid, a significant reduction of the frequency of occurrence of
      labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836
      +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant
      proliferative changes were observed in the placebo group. These results suggest
      that folate supplementation contributes to regulating rectal cell proliferation
      in patients with long-standing UC. These findings may be significant for
      chemoprevention of colon cancer in these patients.

PMID- 9184783
TI  - Disability and cognitive impairment in the elderly.
AB  - Disability and cognitive impairment show similar patterns of increasing frequency
      with ageing. A review of the published literature shows that there is a cross
      sectional relationship between cognitive impairment and disability, independent
      of demographic, medical, and lifestyle factors. Some instrumental activities of
      daily living (IADL) items appear more specifically related to cognitive
      impairment, but cognition and functional impairment are distinct concepts
      requiring separate assessments. Subjects with low cognitive performances are at
      higher risk of functional impairment in the following years. Cognitive impairment
      as well as disability increase the risk of death and institutionalization.
      Preventive strategies could be directed against the risk factors of cognitive
      impairment and disability, and would aim to delay the onset of dementia.
      Prevention of disability associated with cognitive impairment needs further
      assessment in elderly community-dwellers. Further research is needed to better
      identify the specific areas cognition involved in the disablement process.

PMID- 9184784
TI  - Quantitative analysis of gait in the visually impaired.
AB  - In this comparative study concerning characteristics of independent walking by
      visually impaired persons, we used a motion analyser system to perform gait
      analysis of 15 late blind (age 36-54, mean 44.3 years), 15 congenitally blind
      (age 39-48, mean 43.8 years) and 15 sighted persons (age 40-50, mean 44.4 years)
      while walking a 10-m walkway. All subjects were male. Compared to the sighted,
      late blind and congenitally blind persons had a significantly slower walking
      speed, shorter stride length and longer time in the stance phase of gait.
      However, the relationships between gait parameters in the late and congenitally
      blind groups were maintained, as in the sighted group. In addition, the gait of
      the late blind showed a tendency to approximate the gait patterns of the
      congenitally blind as the duration of visual loss progressed. Based on these
      results we concluded that the gait of visually impaired persons, through its
      active use of non-visual sensory input, represents an attempt to adapt to various
      environmental conditions in order to maintain a more stable posture and to effect
      safe walking.

PMID- 9184785
TI  - Occupational therapy for patients with chronic diseases: CVA, rheumatoid
      arthritis and progressive diseases of the central nervous system.
AB  - A substantial proportion of the patients treated by occupational therapists have
      a chronic disease. The aim of this study was to describe the outlines of
      occupational therapy treatment for three specific groups of chronic diseases:
      progressive neurological diseases, cerebrovascular accident and rheumatoid
      arthritis. A total of 143 therapists, working in 49 occupational therapy
      departments in The Netherlands, were asked to complete a standard registration
      from based on the ICIDH. This form consisted of three sections: (a) patient
      characteristics, (b) occupational therapy diagnosis and treatment goals in terms
      of ICIDH and (c) treatment characteristics. The present study concerns 507
      patients: 102 had progressive neurological diseases (PND), 338 had a CVA and 67
      had rheumatoid arthritis (RA). Our results showed that each patient group was
      characterized by a specific treatment approach. Especially at the level of
      treatment programmes substantial differences between groups were observed.
      Besides the clear differences, similarities in approaches were found between the
      PND and RA group, e.g. total time spent on therapy differed largely between the
      PND and RA patients (both averages 6 h) and the CVA patients (average 14 h).

PMID- 9184786
TI  - Determinants of handicap 1 and 3 years after a stroke.
AB  - A total of 361 consecutive admissions to hospital with acute stroke were followed
      up to examine the determinants of handicap 1 year and 2-3 years later. Handicap
      was measured using the London Handicap Scale, and data were collected on initial
      stroke severity, disability, mood and sociodemographic variables. Ninety-five of
      170 survivors returned handicap questionnaires at 1 year, 102 of 149 survivors at
      2-3 years, and 58 on both occasions. Mean handicap score decreased slightly
      between 1 and 2-3 years (45-48 on a 0-100 scale, 95% confidence interval for
      difference -1 to +7, p = 0.09). At both 1 and 2-3 years handicap was associated
      with pre-stroke disability, 1-year score disability, initial stroke severity and
      mood. Age and sex were associated at 1 year but not at 2-3 years. In multivariate
      analyses disability, stroke severity and mood were independently associated with
      handicap. None of the variables examined predicted change in handicap score. The
      study demonstrates the overriding importance of stroke severity (impairment) and
      disability in determining handicap. In comparison, social variables were less
      important.

PMID- 9184787
TI  - Mechanisms of surfactant dysfunction in early acute lung injury.
AB  - Surfactant dysfunction that occurs during acute lung injury is associated with
      alterations in phospholipid, total protein, and surfactant apoprotein content.
      The functional importance of these changes was examined by characterizing the
      biophysical properties and biochemical composition of lung surfactant from
      endotoxin-treated guinea pigs (LPS) with acute lung injury. Static and dynamic
      lung compliance significantly decreased following endotoxin exposure. Lavage
      fluid demonstrated a neutrophil predominance, and tissue histopathology revealed
      inflammation consistent with acute lung injury. LPS surfactant isolated by
      ultracentrifugation had minimum surface tensions of 21 dynes/cm compared to 2
      dynes/cm among control samples. Biochemical abnormalities in LPS surfactant
      included increased total protein, decreased phosphatidylcholine, and increased
      sphingomyelin, phosphatidylethanolamine, and lysophosphatidylcholine. The
      addition to normal guinea pig surfactant of butanol extracts precipitated from
      lavage fluid of LPS animals and containing known amounts of protein caused
      elevations in minimum surface tensions to > or = 20 dynes/cm at protein to
      phospholipid ratios equivalent to those observed in LPS surfactant pellets.
      Addition of equal amounts of precipitate isolated from control animals had no
      effect on interfacial properties. Furthermore, addition of
      lysophosphatidylcholine and sphingomyelin to normal surfactant to simulate
      composition changes observed in LPS surfactant had minimal effect on surface film
      behavior. The results support the hypothesis that aqueous soluble inhibitors of
      surfactant are generated within the alveolar compartment during acute
      inflammation, and that surfactant dysfunction cannot be accounted for on the
      basis of phospholipid composition changes.

PMID- 9184788
TI  - Subthreshold hyperoxia potentiates TNF-alpha-induced ICAM-1 expression on
      cultured pulmonary microvascular endothelial cells.
AB  - The effects of combined exposure to subthreshold hyperoxia and the inflammatory
      cytokine tumor necrosis factor alpha (TNF-alpha) on the expression of
      intercellular adhesion molecule-1 (ICAM-1) were examined in bovine lung
      microvascular endothelial cells (BLuEC). The expression of total ICAM-1 was not
      affected by 50% hyperoxia conditions alone, indicating that this level is
      subthreshold for BLuEC. In the presence of 5 ng/mL TNF-alpha, which has minimal
      influence on BLuEC alone, the amount of total ICAM-1 expression under 50%
      hyperoxia was higher than that in normoxic conditions (approximately 30%)
      throughout the culture period. The amount of soluble ICAM-1 that has been
      released into the culture medium increased after joint exposure to hyperoxia and
      TNF-alpha. These results suggest that exposure to subthreshold hyperoxia, which
      does not by itself cause damage to the endothelial cells or induce ICAM-1
      expression, potentiates the effects of low-level TNF-alpha exposure.

PMID- 9184789
TI  - Responses to welding fumes: lung injury, inflammation, and the release of tumor
      necrosis factor-alpha and interleukin-1 beta.
AB  - Possible mechanisms were examined whereby welding fumes may elicit injury and
      inflammation in the lungs. The effects of different welding fumes on lung
      macrophages and on the in vivo production of two inflammatory cytokines, tumor
      necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), were
      assessed. Fume was collected during flux-covered manual metal are welding using a
      stainless steel consumable electrode (MMA-SS) and gas metal are welding using a
      mild steel electrode (GMA-MS). For the in vitro study, bronchoalveolar lavage was
      performed on untreated rats to recover lung macrophages, and the effects of the
      welding fumes on macrophage viability and respiratory burst were examined. In
      vivo, additional rats were intratracheally instilled with the welding fumes at a
      dose of 1 mg/100 g body weight. These rats were lavaged 1, 14, and 35 days
      postinstillation, and indicators of lung damage (cellular differential, albumin.
      TNF-alpha and IL-1 beta release, and lactate dehydrogenase and beta-n-acetyl
      glucosaminidase activities) were measured. In vitro, the MMA-SS fume was more
      cytotoxic to the macrophages and induced a greater release of reactive oxygen
      species as measured by the respiratory burst compared to the GMA-MS fume. In
      vivo, evidence of lung damage was observed for both fumes 1 day postinstillation.
      By 14 days, lung responses to the GMA-MS fume had subsided and were not different
      from the saline vehicle control group. Significant lung damage was still observed
      for the MMA-SS group at 14 days, but by 35 days, the responses had returned to
      control values. One day after the instillations, both welding fumes had
      detectable levels of TNF-alpha and IL 1 beta within the lavage fluid. However,
      the MMA-SS particles caused a significantly greater release of both cytokines in
      the lavage fluid than did the GMA-MS group. The results demonstrate that MMA-SS
      fume caused more pneumoloxicity than GMA-MS. This increased response may reflect
      enhanced macrophage activation, the increased production of reactive oxygen
      species, as well as secretion of TNF-alpha and IL-1 beta.

PMID- 9184790
TI  - Further investigation of the use of intratracheally administered hyaluronic acid
      to ameliorate elastase-induced emphysema.
AB  - Previously, this laboratory has shown that intratracheally administered
      hyaluronic acid (HA) significantly reduces air-space enlargement in a hamster
      model of emphysema induced with pancreatic elastase. Whereas HA was given
      immediately following elastase in those initial studies, the current
      investigation determined the effect of instilling HA up to 2 h before or after
      intratracheal administration of elastase to hamsters. Both 1 and 2 mg HA, given 2
      h before pancreatic elastase, significantly decreased (p < .05) air-space
      enlargement compared to controls (as measured by the mean linear intercept).
      Instillment of 2 mg HA, 1 h after pancreatic elastase, had a similar effect (p <
      .05). In contrast, 1 mg HA, given 1 or 2 h after pancreatic elastase, did not
      significantly affect the mean linear intercept. Against human neutrophil
      elastase, HA exhibited the same protective effect. While neutrophil elastase
      induced less air-space enlargement than pancreatic elastase, both 1 and 4 mg of
      HA, given 2 h prior to the enzyme, still produced a significant reduction (p <
      .05) in the mean linear intercept. HA exerted this effect despite the fact that
      it initiates a transient influx of neutrophils into the lung. Since HA does not
      slow the clearance of intratracheally instilled [14C] albumin from the lung, its
      mechanism of action may not involve physical interference with the movement of
      elastase through the lung, but may instead depend on interaction with elastic
      fibers. Evidence for an association between these two matrix constituents was
      provided by studies using fluorescein-labeled HA. Overall, these results further
      suggest that HA may be useful in preventing lung injury by elastases.

PMID- 9184791
TI  - Surfactant secretion by type II pneumocytes is inhibited by high glucose
      concentrations.
AB  - Delayed fetal lung maturation is observed in poorly controlled diabetic
      pregnancies. To investigate whether elevated glucose levels inhibit basal
      surfactant secretion and synthesis in type II cells and whether inhibitory
      effects on secretion can be reversed by secretagogues, type II cells isolated
      from 20-day fetal rat lung explants were initially cultured in [H3] choline
      containing media with glucose concentrations of 5.5, 10, 25, 50, and 100 mM, or
      in equiosmolar mannitol controls. Further incubation in nonradioactive media
      containing matched glucose levels with and without 1 x 10(-5) M terbutaline 1 x
      10(-6) M and 1 x 10(-8) M 12-O-tetradecanoylphorbol 13-acetate (TPA) allowed
      assessment of incorporation of choline into phosphatidylcholine (PC) and its
      subsequent secretion. PC secretion was inhibited by culture in high glucose
      conditions, resulting in an approximately 30% reduction in secretion under 50 and
      100 mM glucose conditions compared to culture at 5.5 or 10 mM glucose (p < .01);
      this decrease could not be explained by changes in osmolarity or in all viability
      after culture in high glucose. Insulin (1 unit/mL) had no significant impact on
      secretion (92 +/- 7% of control). Terbutaline-stimulated cells grown under 50 and
      100 mM glucose conditions had significantly lower secretion rates than did
      terbutaline-stimulated cells cultured in 5.3 mM glucose (p < .05). Exposure to
      TPA resulted in significant increase in surfactant secretion by cells grown in
      both 5.5 and 100 mM glucose; however, the percentage increase (39.5 +/- 6.8% and
      94.8 +/- 8.0% with 10(-8) M and 10(-6) MTPA, respectively) was significantly
      lower than in controls (87.8 +/- 8.0% and 152.1 +/- 18.8%, respectively) (p <
      .001). Choline incorporation into PG was also decreased by 100 mM glucose to 77
      +/- 9% of control (p < .01). These data indicate that high glucose levels inhibit
      both surfactant synthesis and baseline and secretagogue-stimulated surfactant
      secretion by type II cells. This inhibitory effect on surfactant secretion may
      further exacerbate the decrease in surfactant synthesis and the pulmonary
      maturational delay seen in infants of diabetic pregnancies.

PMID- 9184792
TI  - Effects of hydrostatic pressure on permeability of airway epithelium.
AB  - The presence of blood proteins and excess liquid in the airway lumen during
      airway inflammation may be secondary to extravasation and elevation of
      subepithelial hydrostatic pressure. This study examines how hydrostatic pressures
      of 5-20 cm H2O affect hydraulic conductivity and macromolecular permeability of
      primary cultures of bovine tracheal epithelium. Hydraulic conductivity was not
      altered by transepithelial pressure gradients of up to 20 cm H2O directed from
      the mucosal to serosal side of the tissue (m-s). By contrast, a 20-cm H2O s-m
      pressure resulted in a marked increase in hydraulic conductivity with the
      critical pressure lying between 10 and 20 cm H2O. Electrical conductance (i.e.,
      permeability to ions) was not altered by m-s pressure gradients, or by a 5-cm H2O
      s-m gradient, but was increased by s-m pressures > or = 10 cm. Fluxes (s-m and m
      s) of fluorescein and fluorescent dextrans (70 and 2000 kDa) were not altered by
      pressures of up to 20 cm H2O m-s. By contrast s-m pressure gradients of 20 cm H2O
      dramatically increased the s-m fluxes of these probes. The increases in flux were
      completely reversible. The results indicate that s-m pressure gradients greatly
      increase the hydraulic conductivity of airway epithelium by creating pores with
      an effective diameter greater than 54 nm.

PMID- 9184793
TI  - Effects of diesel exhaust particles on the release of interleukin-1 and tumor
      necrosis factor-alpha from rat alveolar macrophages.
AB  - The effects of diesel exhaust particles (DEP) and their components (washed dust
      and methanol extracts) on the release of proinflammatory cytokines, interleukin-I
      (IL-1), and tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages (AM)
      were investigated. Rat AM were incubated with 0, 5, 10, 20, 50, or 100
      micrograms/10(6) AM/mL of DEP, methanol-washed DEP, or equivalent concentrations
      of DEP methanol extracts at 37 degrees C for 24 h. AM-conditioned supernatants
      were collected and assayed for the activities of IL-1 and TNF-alpha. At high
      concentrations both DEP and DEP methanol extracts were shown to increase IL-I
      like activity secreted by AM, whereas methanol-washed DEP had no effect. Neither
      DEP, methanol-washed DEP, nor DEP methanol extracts was found to stimulate the
      secretion of TNF-alpha. The effects of DEP on the release of IL-I and TNF-alpha
      by lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-primed AM were also
      studied. AM were preincubated with various concentrations of DEP for 2 h, then
      challenged with either 0.1 microgram/mL of LPS or 5 units/mL of IFN-gamma. DEP
      inhibited LPS-stimulated production of H-I and TNF-alpha. These inhibitory
      effects were attributed to the organic extracts of DEP. In contrast, stimulation
      of AM production of TNF-alpha by IFN-gamma was not affected by DEP exposure. In
      summary, evidence that DEP enhanced the production of IL-1 by AM in vitro
      suggests that this proinflammatory cytokine may play a role in the pulmonary
      response to DEP inhalation. The suppressive response of DEP-pretreated AM to LPS
      stimulation may be a contributing factor to the impairment of pulmonary defense
      system after prolonged DEP exposure.

PMID- 9184794
TI  - The pharmacology of excitatory and inhibitory amino acid-mediated events in the
      transmission and modulation of pain in the spinal cord.
AB  - 1. The aim of this review is to consider the relative roles of inhibitory and
      excitatory amino acid receptor-mediated events in the processes leading to pain
      transmission in the spinal cord. 2. Emphasis will be on the roles of the
      inhibitory and excitatory amino acids, GABA and glutamate, and how the relative
      balance between activity in these systems appears to determine the level of pain
      transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been
      implicated in the generation and maintenance of central (spinal) states of
      hypersensitivity. It has been shown that activation of this receptor underlies
      wind-up, whereby the level of transmission of noxious messages is potentiated.
      Antagonists at this receptor-channel complex prevent or block enhanced
      (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage
      and ischemia. 4. Information concerning amplification systems in the spinal cord,
      such as the NMDA receptor, is a step toward understanding why and how a painful
      response is not always matched to the stimulus. Such events have parallels with
      other plastic events such as long-term potentiation (LTP) in the hippocampus. 5.
      However, the roles of inhibitory transmitter systems can also change insofar as
      opioid, adenosine and GABA transmission in the spinal cord can vary in different
      pain states. 6. Changes in GABA systems have been well-documented and discussion
      will center on whether this has clinical implications. 7. In addition to
      behavioral and electrophysiological approaches to the pharmacology of pain the
      current status of the use of markers of early onset genes such as c-fos, as
      monitors of activity, will be discussed. 8. Hyperalgesia would appear to be
      balanced by inhibitions during inflammatory conditions but not in neuropathic
      states, pains due to nerve damage. In the latter case, events reminiscent of LTP
      may predominate, whereas they are held in check by inhibitions under conditions
      of inflammation.

PMID- 9184795
TI  - Multidrug resistance-associated protein: a protein distinct from P-glycoprotein
      involved in cytotoxic drug expulsion.
AB  - 1. Multidrug resistance (MDR) is a phenomenon originally seen in cultured tumor
      cells that, following selection for resistance to a single anticancer agent,
      become resistant to a range of chemically diverse anticancer agents. These MDR
      cells show a decrease in intracellular drug accumulation due to active efflux by
      transporter proteins. The transporter best characterized is P-glycoprotein (Pgp).
      This protein has been identified in many cancers and has been the target for
      agents able to inhibit its action, thereby reversing resistance. 2. More
      recently, another transporter, multidrug resistance-associated protein (MRP) has
      been identified in a number of MDR human tumor cell lines that do not apparently
      express Pgp. The presence of MRP at the cell surface of these cells is associated
      with alterations in drug accumulation and distribution. 3. The gene-encoding MRP
      has been cloned and sequenced and shown by transfection studies to be able to
      confer resistance and changes in drug accumulation in sensitive tumor cells. The
      profile of anticancer drugs expelled in the presence of MRP is similar, but not
      identical, to that of Pgp. 4. MRP has been identified in a number of different
      types of cancers, but it is not yet clear to what extent it is involved with
      clinical resistance. Furthermore, resistance modulators useful against Pgp are
      less effective in reversing MRP-mediated resistance. 5. It is not fully
      understood how MRP brings about drug efflux, but it is clear that the underlying
      mechanisms are different from those responsible for Pgp-mediated drug efflux. In
      particular, glutathione (GSH) is required for the effective expulsion of the
      anticancer agents. 6. Unlike Pgp, MRP is able to transport metallic oxyanions and
      glutathione and other conjugates, including peptidyl leukotrienes. Agents that
      inhibit organic anion transport, such as probenecid, can block MRP activity. 7.
      Like Pgp, MRP is expressed not only in resistant tumor cells, but also in normal
      human tissues. These include the epithelial cells lining the airways and the
      gastrointestinal tract. In cells in normal tissues, MRP appears to be located
      within the cytoplasm, which may mean that it functions here in a manner slightly
      different to that in malignant cells. It is now also recognized in cells and
      tissues from other species, such as the rat and mouse.

PMID- 9184796
TI  - Recent progress in understanding aldosterone secretion.
AB  - 1. The synthesis and secretion of aldosterone in the adrenal zona glomerulosa in
      physiologic conditions is controlled by adrenocorticotropin (ACTH), angiotensin
      II (AII), and extracellular (K+). 2. ACTH effects on aldosterone output are
      explained by cyclic AMP-(cAMP)- and Ca(2+)-dependent mechanisms. 3. All effects
      on aldosterone secretion are initiated by an increase in Ca2+ influx through
      hormone-operated Ca2+ channels and G-protein- and phospholipase C-(PLC) dependent
      hydrolysis of phosphoinositides leading to the generation of inositol 1,4,5
      trisphosphate (IP3) and DAG that induce intracellular Ca2+ release and PKC
      activation, respectively. 4. ACTH increases DAG formation with marginal or
      undetectable IP3 generation. The effect of ACTH on DAG levels is discussed. 5.
      The requirement of external Ca2+ in PLC activation and aldosterone secretion also
      is discussed.

PMID- 9184797
TI  - Effect of nicotine on the intimal hyperplasia after endothelial removal of the
      rabbit carotid artery.
AB  - 1. The present experiments were designed to investigate the effect of long-term
      oral nicotine (10 mg/200 ml/kg/day for 7 weeks) on the intimal hyperplasia after
      endothelial removal of the rabbit carotid artery. 2. The plasma concentrations of
      nicotine were determined to be 11.7-12.5 ng/ml during the term of administration
      and corresponded to the plasma levels in human smokers. 3. Six weeks after the
      endothelial removal, light microscopy revealed a marked intimal hyperplasia.
      Administration of nicotine tended to accelerate the intimal hyperplasia, which
      was estimated by comparing the histological findings, DNA content and wet weight
      of the vessel wall. 4. Acetylcholine- and A23187-induced endothelium-dependent
      relaxations were greatly impaired in the hyperplastic artery strips. The
      impairment of relaxations tended to be accelerated in the nicotine group. Sodium
      nitroprusside-induced relaxation was not different between the control and the
      hyperplastic artery strips and remained unaffected in the nicotine group. 5. The
      concentrations of endogenous nitric oxide (NO) synthesis inhibitors, NG
      monomethyl-L-arginine (L-NMMA) and asymmetrical NG,NG-dimethyl-L-arginine (ADMA)
      were significantly more increased in the regenerated endothelial cells compared
      with those in the control endothelial cells. The concentrations of L-NMMA and
      ADMA in the regenerated endothelial cells were significantly increased by as much
      as 1.3 x 10(-6) and 5.6 x 10(-7) M, respectively, in the nicotine group. 6.
      Immunoreactive endothelin-1 was significantly increased in the hyperplastic
      vessel wall (2.4 times that of the control) in 6 weeks. Administration of
      nicotine tended to increase the level. 7. It seems possible to assume from these
      results that, although, under the present experimental conditions, nicotine
      exhibited a tendency to accelerate the intimal hyperplasia after endothelial
      removal, the longer exposure to nicotine or a higher dose of the agent or both
      would significantly accelerate the intimal hyperplasia through the enhanced
      impairment of endothelium-derived relaxing factor/ NO production, which might be
      brought about by the enhanced increases in L-NMMA and ADMA concentrations, and
      the enhanced increase in endothelin-1 in the vessel wall.

PMID- 9184798
TI  - Opposite effects of sex steroids on 11 beta-hydroxysteroid dehydrogenase activity
      in the normal and adrenalectomized rat testis.
AB  - 1. Sex steroids have been shown to regulate the biosynthesis of 11 beta
      hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that
      oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme
      activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11
      beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar
      rats was determined following a daily IM injection of sex steroids for 7 days. 4.
      The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T
      in normal and ADX rats. The enzyme activity in normal rats given both T and E2
      was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal
      and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The
      presence of corticosteroids influenced the effects of E2, but not of T and P4, on
      11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4
      increased it. E2 did not act through lowering T level.

PMID- 9184799
TI  - Sematilide blocks the inward rectifier potassium channel in isolated guinea pig
      ventricular myocytes.
AB  - 1. In whole-cell patch recording, the relative potency of the blocking action of
      sematilide on IK1 was found to be constant at each potential level of IK1
      activation. Under more acidic condition, the degree of block was decreased. These
      results strongly suggested that the neutral form of sematilide may penetrate the
      cardiac cell membrane via hydrophobic pathway. 2. In cell-attached patches,
      sematilide prolonged the interburst interval and reduced the opening
      probabilities of the IK1 channel without affecting either the mean open time or
      the mean closed time within a burst.

PMID- 9184800
TI  - Different roles of endothelium-derived substances on inhibiting platelet
      aggregation in whole blood.
AB  - 1. The inhibitory effects of adenosine, nitroprusside (a nitric oxide donor) and
      prostacyclin on collagen-induced rabbit platelet aggregation were studied under
      two different conditions: in whole blood with an impedance method and in platelet
      rich plasma (PRP) with a turbidimetric method. 2. All substances tested were less
      potent in whole blood than in PRP, and the differences in IC50 value between
      whole blood and PRP were not of the same order of magnitude; adenosine (669
      fold), nitroprusside (54-fold) and prostacyclin (2-fold). 3. These results imply
      that (a) some other, as yet unknown, factors in blood modulate the platelet
      aggregation; (b) adenosine and nitric oxide act close to the endothelium, and (c)
      prostacyclin acts as a relatively long lasting circulating hormone.

PMID- 9184801
TI  - Inhibition of a Porphyromonas gingivalis colonizing factor between Actinomyces
      viscosus ATCC 19246 by monoclonal antibodies against recombinant 40-kDa outer
      membrane protein.
AB  - 1. Porphyromonas gingivalis, an important pathogen in human periodontal disease,
      aggregates with Actinomyces viscosus ATCC 19246. 2. Monoclonal antibodies (mAbs)
      against purified recombinant 40-kDa outer-membrane protein (r40-kDa, OMP) of P.
      gingivalis 381 inhibited its coaggregation with A. viscosus ATCC 19246 in a dose
      dependent manner. 3. Five mAb clones against r40-kDa OMP were selected. The
      isotype of the five was IgG1. 4. Pg-ompA2 inhibited the coaggregation of several
      strains of P. gingivalis with A. viscosus ATCC 19246 cells.

PMID- 9184802
TI  - Differential modulation by the endothelium of contractile responses to 5
      hydroxytryptamine, noradrenaline, and histamine in the rabbit isolated basilar
      artery.
AB  - 1. To assess modification by endothelium, we determined the contractile responses
      of intact rings from rabbit basilar artery to histamine, noradrenaline and 5
      hydroxytryptamine (5-HT) and compared them with Triton X-100-treated and NG-nitro
      L-arginine (L-NNA)-treated preparations. 2. Among the agonists examined histamine
      caused the strongest contraction of vascular smooth muscles and noradrenaline the
      weakest one. The present results are consistent with the basal release of
      endothelial-derived relaxing factor (EDRF). 3. 5-HT caused a much greater
      modification than the one expected from basal release of EDRF, suggesting that
      the release is induced by 5-HT, in contrast to the previous results. Our findings
      also indicate that 5-HT could induce the release of both contracting factor
      (EDCF) and EDRF from the endothelium.

PMID- 9184803
TI  - Inhibition of voltage-dependent Ca2+ channels of porcine tracheal smooth muscle
      by the novel Ca2+ channel antagonist RWJ-22108.
AB  - 1. We compared electrophysiological effects of the bronchoselective Ca2+ channel
      antagonist RWJ-22108 on voltage-dependent Ca2+ channels (VDCs) of porcine
      tracheal smooth muscle cells to the effects of nicardipine and verapamil. 2. Each
      of the three Ca2+ channel antagonists tested inhibited inward Ca2+ currents (ICa)
      measured by whole-cell patch clamp techniques. Inhibition was dose-dependent with
      approximately 50% inhibition of peak ICa at +20 mV obtained with 3 x 10(-6) M RWJ
      22108, 3 x 10(-7) M nicardipine, or 10(-5) M verapamil. 3. Both RWJ-22108 (3 x
      10(-6) M) and nicardipine (3 x 10(-7) M) shifted the voltage dependence of steady
      state inactivation to more negative potentials; however, the change in the
      potential of half-maximal inactivation induced by RWJ-22108 (-18 mV) was
      significantly greater than that induced by nicardipine (-12 mV). Verapamil did
      not alter the voltage dependence of inactivation. 4. We conclude that inhibition
      of VDCs by RWJ-22108 is qualitatively similar to that by nicardipine but with a
      greater stabilizing effect on the inactivated channel state.

PMID- 9184804
TI  - Pharmacokinetic profile of piroxicam beta-cyclodextrin, in rat plasma and lymph.
AB  - 1. The absorption of piroxicam into the blood of rats is significantly slower
      after oral administration of piroxicam beta-cyclodextrin than of free piroxicam.
      2. The pharmacokinetic profiles of piroxicam in rat lymph were very similar in
      both groups. 3. Bioavailability of piroxicam in plasma is higher after treatment
      with the inclusion product than with free piroxicam. On the other hand,
      bioavailability in lymph is higher when free piroxicam is administered.

PMID- 9184805
TI  - Action of the extract of Drymis winteri on contraction induced by inflammatory
      mediators, compound 48/80 and ovalbumin of the guinea-pig trachea in vitro.
AB  - 1. We examined the effect of hydroalcoholic extract (HE), obtained from the barks
      of Drymis winteri J.R. et Forster (Winteraceae), against contraction caused by
      several mediators involved in asthma and allergy, and also that caused by
      ovalbumin and compound 48/80 in guinea-pig trachea. 2. HE (0.5-2 mg/ml) added to
      the bath 20 min earlier antagonized the contractions elicited by bradykinin,
      prostaglandin E2 and capsaicin in a concentration-dependent and noncompetitive
      manner. 3. HE antagonized, in a graded but apparently competitive fashion,
      contractions induced by substance P, [beta-ala8]neurokinin A-(4-10), a selective
      NK2 agonist, and the stable analog of thromboxane A2 (U 46619). However, HE had
      only a slight effect against contractions induced by histamine and had no effect
      against responses induced by acetylcholine and the selective NK1 agonist,
      substance P-methylester. 4. In guinea-pig trachea (GPT) from animals that had
      been previously sensitized actively to ovalbumin, HE antagonized ovalbumin
      mediated contraction in a time- and concentration-dependent manner. In addition,
      HE caused graded displacement to the right of contraction evoked by compound 48/
      80 in GPT from nonsensitized animals. 5. It is concluded that HE contains active
      principle(s) which interact via distinct mechanisms with several mediators known
      to participate in asthma and allergy. Furthermore, HE concentration dependently
      attenuated ovalbumin and compound 48/80-mediated contractions in GPT from
      sensitized and nonsensitized animals, respectively.

PMID- 9184806
TI  - Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori
      lipopolysaccharide with ebrotidine and sulglycotide.
AB  - 1. Among the consequences of H. pylori infection is an increase in gastric acid
      secretion due to the impairement in feedback inhibition by somatostatin. Here, we
      show that lipopolysaccharide from H. pylori inhibits the binding of somatostatin
      to gastric mucosal receptor, and that antiulcer agents, ebrotidine and
      sulglycotide, are capable of countering this effect. 2. The somatostatin receptor
      was prepared from the solubilized gastric mucosal epithelial cell membranes by
      affinity chromatography on Affi-Gel-bound [D-Tryp8] SRIF-14 and used in the
      binding assays for 125I-labeled somatostatin in the presence of H. pylori
      lipopolysaccharide and antiulcer agents. 3. The assays revealed a dose-dependent
      inhibition in the receptor-somatostatin binding by the lipopolysaccharide which
      reached a maximum of 94.1%. The effect of H. pylori lipopolysaccharide was
      countered by ebrotidine and sulglycotide, which at their optimal doses produced
      94.9% and 84% restoration in somatostatin-receptor binding, respectively. 4. The
      results demonstrate that the antiulcer agents, ebrotidine and sulglycotide,
      possess the ability to counteract the H. pylori interference with somatostatin
      regulatory effect on gastric acid secretion.

PMID- 9184807
TI  - Studies investigating the possible involvement of adenosine in the antisecretory
      action of morphine.
AB  - 1. Fluid secretion was induced in the jejunum of anesthetised rats using
      vasoactive intestinal peptide. 2. The adenosine antagonist, DPCPX (0.1 mg/kg),
      suppressed the antisecretory action of morphine (10 mg/kg), but naloxone (80
      micrograms/kg) did not inhibit the antisecretory response of the adenosine
      agonist, NECA (40 micrograms/kg), at a dose previously shown to antagonize the
      antisecretory response of morphine. 3. NECA (40 (micrograms/kg) reversed
      secretion in pithed and reserpine-pretreated (5 mg/kg subcutaneously) rats. 4. It
      is proposed that adenosine acts as a mediator of the morphine antisecretory
      effect at a site distal to the noradrenergic neurons involved in the action of
      morphine.

PMID- 9184808
TI  - Neurochemical actions of vigabatrin and tiagabine alone and in combination in
      mouse cortex.
AB  - 1. The effects of repeated administration of the anticonvulsant compounds,
      vigabatrin (VGB) and tiagabine (TGB), on gamma-aminobutyric acid (GABA)
      concentration and the activities of GABA-transaminase (GABA-T) and glutamic acid
      decarboxylase (GAD) were investigated in mouse cortex. 2. VGB alone increased
      GABA levels and decreased GABA-T and GAD activities. 3. TGB alone was essentially
      without effect. 4. Low doses of VGB and TGB in combination increased GABA levels
      when neither drug had such an effect alone. 5. Despite this observation, this
      study failed to establish any conclusive evidence for an interaction between VGB
      and TGB that might help to explain their reported clinical synergism.

PMID- 9184809
TI  - Alpha 1-adrenoceptor subtype involved in the positive and negative inotropic
      responses to phenylephrine in rat papillary muscle.
AB  - 1. In rat papillary muscle, stimulation of alpha 1-adrenoceptors results in a
      biphasic inotropic response: a transient negative inotropic phase and a
      subsequent sustained positive inotropic phase. This study was designed to
      determine whether the positive and negative inotropic effects in this tissue are
      mediated by different alpha 1-adrenoceptor subtypes. 2. After treatment with the
      tumor-promoting compound, phorbol 12, 13-dibutyrate, phenylephrine (in the
      presence of propranolol) produced only a positive inotropic effect. The selective
      alpha 1A-adrenoceptor antagonist, WB4101, significantly inhibited the positive
      inotropic effect. In contrast, inactivation of alpha 1B-adrenoceptors with
      chloroethylclonidine (CEC) did not alter the positive effect. 3. In the presence
      of the Ca2+ channel antagonist, nifedipine, phenylephrine induced only a
      sustained negative inotropic effect. The negative inotropic effect was
      significantly attenuated by WB4101, but was not affected by CEC. 4. We conclude
      that both the positive and negative inotropic responses of rat papillary muscle
      to phenylephrine are mediated exclusively by the WB4101-sensitive but CEC
      resistant alpha 1-adrenoceptor subtype. The alpha 1-adrenoceptor subtype with
      such a property may correspond to the alpha 1A-subtype.

PMID- 9184810
TI  - Increased toxicity of methamphetamine in morphine-dependent mice.
AB  - 1. The effect of methamphetamine on morphine-dependent mice was investigated by
      calculating the LD50 (i.p.), measuring motor activity, anorectic actions, and
      body temperature. 2. Methamphetamine was more toxic in morphine-dependent mice
      (LD50 = 20.6 mg/kg) than in normal mice (LD50 = 43.2 mg/kg). 3. Methamphetamine
      induced locomotor activity was greater in morphinized than in nonmorphinized mice
      at doses of 2.5 and 5 mg/kg i.p. 4. Methamphetamine also increased the body
      temperature of morphinized mice more than that of normal mice (P < 0.05). 5.
      These findings suggest that methamphetamine is more toxic in morphine-dependent
      than in nondependent mice.

PMID- 9184811
TI  - Defibrotide augments the anticandidial activity of NK cells.
AB  - 1. The mechanism of action of Defibrotide, a fibrinolytic agent on Natural Killer
      (NK) cell cytotoxicity, was investigated through verapamil, TMB-8 cells and
      pertussis toxin. 2. Defibrotide increased the activity against Candida albicans
      cells (anticandidial activity), and it is determined that the calcium channels
      have a role in this effect. 3. Blockage of calcium channels reduced the
      anticandidial effect by 39.2%. Pertussis toxin led to a 10.7% inhibition, whereas
      the application of TMB-8 resulted in the stimulation of anticandidial activity.
      4. It is concluded that defibrotide is a potent activator of NK cells.

PMID- 9184812
TI  - Multiple vasoactive factors in epidermal secretions of the Arabian Gulf catfish,
      Arius bilineatus (Valenciennes).
AB  - 1. The Arabian Gulf catfish produces proteinaceous epidermal secretions when
      threatened or injured. 2. The soluble fraction of the catfish epidermal
      secretions (SES) has vasoconstrictor activities on sheep renal arteries, which
      can be inhibited by several antagonists, including atropine, indomethacin,
      prazosin, and verapamil. 3. Mepyramine, yohimbine, and ketanserin have negligible
      effects on SES-induced contraction. 4. SES exhibits a significant tachyphylaxis
      upon addition of a second (8.4% reduction) and third (47% reduction) dose of SES
      to the organ bath, which can be partially prevented by addition of a fresh
      arterial section prior to each addition. 5. A vasoconstricting activity has been
      partially purified from SES by gel filtration on Fractogel HW-65(F) and appears
      to be a protein with a pI near 7.3. This activity is affected only by verapamil
      and prazosin.

PMID- 9184813
TI  - The role of endothelium in the calcium-induced reduction of the contractile
      response of the rabbit aorta.
AB  - 1. Increase of Ca2+ concentration in the bath solution diminishes the contractile
      response of isolated rabbit aorta rings to alpha 1-adrenoceptor agonists and KCl.
      2. In intact preparations the contractions of methoxamine and phenylephrine were
      maximal when a 0.3- to 0.6-mM Ca2+ bath solution was used, and those of KCl were
      maximal with a 2.5-mM Ca2+ concentration. 3. The contractions of methoxamine and
      phenylephrine also were decreased by increasing the Ca2+ concentration above 1.25
      mM in disrupted endothelium preparations and in those incubated in indomethacin
      (10(-5) M), N omega-nitro-L-arginine methyl ester (10(-4) M), or methylene blue
      (10(-6) M). 4. High organ bath Ca2+ concentrations also caused a decrease in KCl
      contractions using endothelium-denuded and the treated preparations, the
      responses being similar with 1.25 mM and 2.5-mM Ca2+ in the methylene blue
      treated preparations, whereas they were greater with 1.25 mM Ca2+ in the others.

PMID- 9184814
TI  - Potentiation of the relaxing action of isoproterenol by forskolin in rabbit
      aortic rings: the involvement of beta 2-adrenoceptors.
AB  - 1. Forskolin, an activator of adenylate cyclase, potentiated the relaxing
      response to isoproterenol in rabbit aortic rings precontracted by phenylephrine
      (PE). 2. The potentiating effect of forskolin was inhibited by propranolol, a
      beta-adrenoceptor inhibitor, but not by methylene blue, a guanylate cyclase
      inhibitor. 3. The relaxing response to terbutaline, a beta 2-adrenoceptor
      agonist, but not lower concentrations of dobutamine, a beta 1-adrenoceptor
      agonist, also was potentiated by forskolin. Forskolin, however, potentiated the
      relaxing response to high concentrations of dobutamine, which activates both beta
      1- and beta 2-adrenoceptors. 4. Yohimbine, an alpha 2-adrenoceptor inhibitor,
      glyburide, an ATP-sensitive K+ channel inhibitor, iberiotoxin, a Ca(2+)-activated
      K+ channel inhibitor, or endothelium-removal failed to affect the potentiating
      effect of forskolin. 5. Dibutyryl cyclic AMP (cAmp) also potentiated the relaxing
      response to terbutaline. 6. These results suggest that in rabbit aortic rings
      forskolin causes the apparent potentiation of isoproterenol-induced relaxation by
      mainly affecting the relaxing response due to the activation of beta 2
      adrenoceptors by the forskolin-induced increase in the level of cAMP.

PMID- 9184815
TI  - The mechanism of the relaxing effect of ascorbic acid in guinea pig isolated
      tracheal muscle.
AB  - 1. The effect of ascorbic acid was studied in the guinea pig isolated tracheal
      muscle. 2. Ascorbic acid with relatively higher concentrations produced a dose
      dependent relaxation in tracheal muscle submaximally precontracted with KCl,
      histamine, and carbachol. 3. Removing the epithelium did not significantly alter
      the relaxing effect of ascorbic acid in histamine- and KCl-precontracted strips.
      4. The relaxing effect of ascorbic acid is stronger in carbachol-precontracted
      epithelium-denuded strips than in epithelium-intact strips. 5. Indomethacin, but
      not L-NAME, partially inhibited the relaxing effect of ascorbic acid. 6. These
      results indicate that the relaxation induced by ascorbic acid in guinea pig
      isolated tracheal muscle does not fully depend on the presence of epithelium but
      is partially mediated by the production of prostanoids from smooth muscle.

PMID- 9184816
TI  - Effects of 9-amino-1,2,3,4-tetrahydroacridine (THA) on ATP diphosphohydrolase (EC
      3.6.1.5) and 5'-nucleotidase (EC 3.1.3.5) from rat brain synaptosomes.
AB  - 1. 9-Amino-1,2,3,4-tetrahydroacridine (THA), an acetylcholinesterase inhibitor,
      significantly inhibited in vitro the ATP diphosphohydrolase activity of
      synaptosomes from the cerebral cortex and hippocampus of adult rats. 2. THA did
      not inhibit in vitro the 5'-nucleotidase activity of synaptosomes from cerebral
      cortex and hippocampus of rats. 3. THA exerted an uncompetitive inhibition on ATP
      diphosphohydrolase activity. This mechanism of inhibition was the same in the 2
      different synaptosomal fractions (cerebral cortex and hippocampus) studied. 4.
      THA, proposed as a drug for the treatment of Alzheimer's disease, can alter in
      vitro ATP degradation in synaptosomes from the central nervous system.

PMID- 9184817
TI  - Pharmacological effects of selected flavonoids on rat isolated ileum: structure
      activity relationship.
AB  - 1. Eleven selected flavonoids were studied to evaluate their effects on the rat
      isolated ileum and to determine their structure-activity relationships. 2. The
      flavonoids rutin and 3',5,7-trihydroxy-4' methoxyflavone-7-rutinoside, which have
      a sugar moiety (O-rha-glu), had no significant effect on the ileum, indicating
      that the presence of sugar substitution reduces the biological activity of the
      flavonoids. 3. Nine other flavonoids caused inhibition of tonic and phasic
      contractions of the ileum with the following order of potency from highest to
      lowest: galangin, quercetin, chrysin, xanthomicrol, flavone, naringenin, fisetin,
      morin, and flavanone. 4. Flavones were more potent than flavanones, indicating
      that the double bond at carbon 2-3 increases the potency of the flavonoid. 5.
      Galangin, quercetin, chrysin, and xanthomicrol, which have hydroxyl substituents
      on carbon 3 and/or 5, showed higher potency than flavone, indicating that such
      hydroxyl groups are essential for the activity. 6. Galangin was more potent than
      quercetin, morin, and fisetin, suggesting that the hydroxyl substituents on ring
      B attenuate the potency. 7. Quercetin caused more potent relaxation of the ileum
      than morin, suggesting that the presence of a hydroxyl group at C-2' of ring B
      attenuates the myolytic activity.

PMID- 9184818
TI  - The effects of amrinone and glucagon on verapamil-induced myocardial depression
      in a rat isolated heart model.
AB  - 1. We measured the ability of glucagon and amrinone, used alone and in
      combination, to improve the myocardial function in a rat isolated heart model of
      calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol
      consistently decreased heart rate and cardiac contractile force in our
      Langendorff rat isolated heart preparations. Glucagon increased the heart rate in
      a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(
      1) mol concentration, and had no significant effect on cardiac contractility. 3.
      A positive linear correlation was found between the glucagon concentration and
      the percent recovery of baseline contractile force. 4. Although complete reversal
      of verapamil-induced myocardial depression occurred at glucagon concentrations of
      > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at
      its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were
      administered together, there was no additional increase over glucagon alone in
      the increase in contractile force. 6. Glucagon, and not amrinone, is an
      appropriate agent, capable of reversing verapamil-induced myocardial toxicity in
      this rat isolated heart model. In vivo studies should be performed to assess
      whether this may be a reliable therapy in clinical cases.

PMID- 9184819
TI  - The effects of lithium, indomethacin, and neomycin on vasopressin-induced
      contractions in rat urinary bladder.
AB  - 1. [Arg8]Vasopressin (AVP) induced a contraction response in rat urinary bladder
      smooth muscle in a dose-dependent manner. 2. Indomethacin in a 10-microM
      concentration cannot change the effects of AVP on urinary bladder smooth muscle,
      which seem to be mediated by a direct action on the muscle rather than indirectly
      through prostanoid release. 3. Lithium (0.5, 1, and 10 mM) made the muscle more
      sensitive to AVP action. 4. Neomycin (1.25, 2.5, and 5 mM) had an inhibitory
      effect on AVP-induced contraction. 5. It seems that in rat urinary bladder
      vasopressin-induced contraction is mediated through phosphoinositide metabolism.

PMID- 9184820
TI  - New inotropic agents: milrinone analogs.
AB  - 1. Two new milrinone analogs, 3-acetyl-6-phenyl-2(1H)-pyridone (SF 348) and 3
      acetyl-7-methyl-7,8-dihydro-2,5(1H, 6H) quinolinone (SF 349), increase the
      contractile activity of spontaneously beating and electrically driven atria
      isolated from reserpine-treated guinea-pigs. 2. Propranolol 0.1 microM
      drastically inhibits the contractile effect of SF 348, whereas that of SF 349 is
      unaffected. Preincubation of the atria with adenosine-deaminase suppresses the
      cardiac activity of SF 349, but does not affect that of SF 348. 3. SF 349
      competitively antagonizes the negative inotropic effect induced by N6-(R
      phenylisopropyl)-adenosine (R-PIA) and displaces N6-cyclohexyl[3H]-adenosine (3H
      CHA) from its binding sites to A1 receptors in the guinea-pig heart. 4. The
      positive inotropic effect of SF 348 is largely sustained by activation of beta
      adrenoceptors, whereas SF 349 acts by displacing endogenous adenosine from its
      inhibitory (A1) receptors in the atria.

PMID- 9184821
TI  - Neuromuscular facilitation and blockade induced by L-arginine and nitric oxide in
      the rat isolated diaphragm.
AB  - 1. L-Arginine (4.7-9.5 mM) induced an increase in the amplitude of muscular
      contraction (AMC) evoked by nerve stimulation of rat diaphragm preparations, but
      produced a reduction of the AMC evoked by direct stimulation of muscles
      previously treated with d-tubocurarine. The facilitatory dose of L-arginine was
      ineffective in changing the twitch tension evoked by retrograde injection of
      acetylcholine. 2. N omega-nitro-L-arginine (18 mM) antagonized the increase in
      AMC induced by L-arginine in preparations indirectly stimulated, and a similar
      effect was obtained against the depression induced by L-arginine in directly
      stimulated muscle preparations. D-Arginine (4.5-9.5 mM) was ineffective in
      changing the AMC evoked by direct or indirect stimulation of the diaphragm. 3. NO
      (8.6 mM) induced an increase of the AMC evoked by indirect stimulation of the
      muscle and was ineffective in changing the twitch tension evoked by retrograde
      injection of acetylcholine. NO (8.6 mM) produced an increase followed by a
      reduction of the AMC evoked by direct stimulation of muscles, but the muscular
      facilitatory effect induced by NO was smaller than the neuromuscular facilitatory
      effect. 4. These results indicate that NO increases the AMC when it interacts at
      the presynaptic level and decreases the AMC when it interacts at the postsynaptic
      level.

PMID- 9184822
TI  - Effect of the sulfonylurea glyburide on superoxide dismutase in streptozotocin
      induced diabetic rat muscle.
AB  - 1. The effect of glyburide (glibenclamide) treatment on the muscle superoxide
      dismutase (SOD) activity of diabetic rats has been studied. 2. Four weeks of
      treatment with glyburide (5 mg/kg, orally) increased muscle SOD activity and
      decreased blood glucose levels. 3. The results of this study demonstrate that the
      sulfonylurea, glyburide, is capable of exerting direct insulin-like effects on
      muscle SOD activity in vivo.

PMID- 9184823
TI  - A new substance (Yoshixol) with an interesting antibiotic mechanism from wood oil
      of Japanese traditional tree (Kiso-Hinoki), Chamaecyparis obtusa.
AB  - 1. A neutral wood oil was extracted from Chamaecyparis obtusa (Kiso-Hinoki),
      which has been trusted nationally and preserved historically in the central part
      of Japan (Kiso, Nagano). 2. Hinokitiol, or thujaplicin (C10H12O2), which has been
      believed to exist in Cupressaceae, was not found in this neutral wood oil. Some
      differences between the extracting processes of the natural products are
      discussed. 3. A new chemical substance (Yoshixol, 4,4-dimethyl-6-methylene-2
      cyclohexen-1-one) was simulated by several criteria (details in the text) as a
      major candidate of the neutral wood oil from Chamaecyparis obtusa. Thus, Yoshixol
      was newly synthesized. 4. The antibiotic effects of hinokitiol, the neutral wood
      oil and Yoshixol on methicillin-resistant Staphylococcus aureus (MRSA) were
      examined bacteriologically and morphologically. 5. All of the aforementioned
      three test materials showed complete antibiotic effects on MRSA by the
      bacteriological examination. However, the morphological findings showed entirely
      different aspects of cell death. 6. Hinokitiol caused an aggregative,
      degenerative and/or necrotic aspect, but the neutral wood oil and Yoshixol
      produced characteristic aspects: separation of contacted cells, blebbing, bugging
      like eruption, formation of granules and an extensive reduction of individual
      cell size of MRSA. 7. Yoshixol was able to enhance those antibiotic effects on
      MRSA distinctly more than the neutral wood oil. 8. Yoshixol also showed a strong
      antibiotic effect on Escherichia coli, Mycobacterium chelonei, Pseudomonas
      aureginosa and Candida albicans. Morphological observations of those bacilli
      after Yoshixol revealed characteristic aspects of separation of contacted cells,
      bugging-like swelling, granulation, ballooning and reduction of cell size. 9. A
      possible mechanism of Yoshixol is discussed in regard to a molecular orbital
      theory on the basis of its electron orbits and to a thermodynamic interaction
      with the prokaryotic cell membrane. On the basis of the molecular properties of
      Yoshixol, future biological interests and possible biological effects of Yoshixol
      are suggested.

PMID- 9184824
TI  - Apoptosis-like (possible quantum thermodynamic) cell death induced by Yoshixol
      and wood oil of Chamaecyparis obtusa (Kiso-Hinoki) on HeLa cell.
AB  - 1. We report on the cytotoxic effects of neutral wood oil extracted from
      Chamaecyparis obtusa (Kiso-Hinoki) and of the newly synthetized substance
      Yoshixol (4,4-dimethyl-6-methylene-2-cyclohexen-1-one) on cultured HeLa cells. 2.
      The neutral wood oil produced cell death, led to the formation of granules, which
      were connected with fibrous networks, and reduced cell size. 3. Yoshixol caused a
      separation of cells, granulation, formation of high-density materials (probably
      apoptotic body), and reduction of cell size. 4. DNA fragmentation on the
      electrophoresis was observed with Yoshixol. A low-molecular-weight smear band
      appeared in the supernatant after treatment with the neutral wood oil. Neither
      treatment showed higher lactate dehydrogenase (LDH) activity in the culture
      medium than seen with ethanol as a control. 5. These findings suggest that both
      the neutral wood oil and Yoshixol have a similar cytotoxic mechanism, reducing
      cell size and producing a granulation (fragmentation) of eukaryotic cells. 6.
      Yoshixol may be a potent antitumor agent that induces apoptotic-like cell death.
      This possible mechanism is discussed.

PMID- 9184825
TI  - Synthesis of a new nanomolar saccharide inhibitor of lymphocyte adhesion:
      different polylactosamine backbones present multiple sialyl Lewis x determinants
      to L-selectin in high-affinity mode.
AB  - Lymphocyte infiltration is a hallmark of acute rejections in solid organ
      transplants, such as cardiac allograft. We have previously shown that lymphocyte
      extravasation to cardiac grafts undergoing rejection is largely due to
      interactions between lymphocyte L-selectin and its sialyl Lewis x (sLex)
      decorated ligands. Our previous work demonstrated further that an enzymatically
      synthetized tetravalent sLex glycan of a branched polylactosamine backbone is a
      highly efficient inhibitor of L-selectin-dependent lymphocyte adhesion to graft
      endothelium. To improve the availability of multivalent sLex glycans for anti
      inflammatory indications, we now report enzymatic synthesis of another
      tetravalent sLex glycan that can be potentially produced on a large scale, and
      show that even the new saccharide is a nanomolar inhibitor of L-selectin
      dependent lymphocyte adhesion. The novel antagonist is sLex beta 1-3' (sLex beta
      1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc beta 1-3' (sLex beta 1-6') LacNAc
      (8) (where LacNAc is the disaccharide Gal beta 1-4GlcNac and sLex is the
      tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-4 (Fuc alpha 1-3) GlcNAc). Its five
      step synthesis was started from the octameric polylactosamine LacNAc beta 1-3'
      (GlcNAc beta 1-6') LacNAc beta 1-3' (GlcNAc beta 1-6') LacNAc (3), which in turn
      is accessible in one step from the hexasaccharide LacNAc beta 1-3'LacNAc beta 1
      3'LacNAc. Importantly, the hexasaccharide primer has been synthesized chemically
      (Alais and Veyrieres, Tetrahedron Lett., 24, 5223, 1983). Hence, our data outline
      a route to glycan 8, consisting of a combination of chemical and enzymatic
      methods of oligosaccharide synthesis. In addition, our data show that
      polylactosamine backbones are able to present multiple sialyl Lewis x
      determinants to L-selectin in high-affinity mode, without a requirement for
      uniqueness in the backbone structure.

PMID- 9184826
TI  - A monoclonal antibody directed to terminal residue of beta-galactofuranose of a
      glycolipid antigen isolated from Paracoccidioides brasiliensis: cross-reactivity
      with Leishmania major and Trypanosoma cruzi.
AB  - A mouse monoclonal antibody, MEST-1, was produced against Band 1 glycolipid
      antigen of Paracoccidioides brasiliensis. The glycan structure of Band 1 antigen
      was recently elucidated and the monosaccharides sequence was defined as: Galf
      beta 1-->6(Manp alpha 1-->3)Manp beta 1-->2Ins. The reactivity of MEST-1 MAb was
      determined by solid-phase radioimmunoassay and high performance thin layer
      chromatography immunostaining. Selective oxidation of galactofuranose residues
      and inhibition assays with different methyl-glycosides, revealed that MAb MEST-1
      is directed against the terminal residue of beta-D-galactofuranose of Band 1, a
      phosphoglyceroglycolipid antigen of P. brasiliensis. By indirect
      immunofluorescence, it was observed that the epitope recognized by MEST-1 is
      accessible to the antibody in yeast forms of this fungus. Reactivity of MEST-1
      with parasites known to express galactofuranose containing glycoconjugates was
      also analyzed by indirect immunofluorescence. A positive fluorescence was
      observed with promastigotes of Leishmania major and epimastigotes of Trypanosoma
      cruzi. GIPL-1 was identified as the antigen recognized by MEST-1 in Leishmania
      major, indicating that the MAb MEST-1 recognizes terminal galactofuranose residue
      in either beta 1-->6 or beta 1-->3 linkage to the mannose.

PMID- 9184827
TI  - Mouse beta-galactoside alpha 2,3-sialyltransferases: comparison of in vitro
      substrate specificities and tissue specific expression.
AB  - Four types of beta-galactoside alpha 2,3-sialyltransferase (ST3Gal I-IV) have
      been cloned from several animals, but some contradictory observations regarding
      their substrate specificities and expression have been reported. Therefore, it is
      necessary to concurrently analyze the substrate specificities of the four
      enzymes, of which the source should be one animal. Accordingly, the acceptor
      substrate specificities and gene expression of mST3Gal I-IV were analyzed. Since
      we had already cloned ST3Gal I and II, as previously reported (Lee, Y.-C. et al.,
      Eur. J. Biochem., 216, 377-385 (1993); J. Biol. Chem., 269, 10028-10033 (1994)),
      the cDNAs of ST3Gal III and IV were cloned from mouse cDNA libraries. Each of the
      four enzymes was expressed in COS-7 cells as a recombinant enzyme fused with
      protein A, and applied on an IgG-Sepharose gel to eliminate endogenous
      sialyltransferase activity. ST3Gal I and II showed the highest activity toward
      Gal beta 1, 3 GalNAc (type III), very low activity toward Gal beta 1,3GlcNAc
      (type I), but none toward Gal beta 1,4GlcNAc (type II). ST3Gal III and IV
      exhibited high activity toward the type I and II disaccharides, but very low
      activity toward the type III one. On the other hand, asialo-GM1 (Gg4Cer) was as
      good a substrate for ST3Gal I and II as the type III disaccharide, though ST3Gal
      III and IV hardly utilized glycolipids as substrates, as indicated by in vitro
      experiments. Northern blot analysis revealed that enzymes of the ST3Gal-family
      are expressed mainly in a tissue-specific manner. The ST3Gal I gene was strongly
      expressed in spleen and salivary gland, and weakly in brain, liver, heart,
      kidney, and thymus. The ST3Gal II gene was strongly expressed in brain, and
      weakly in colon, thymus, salivary gland, and testis, and developmentally
      expressed in liver, heart, kidney, and spleen. The ST3Gal III and IV genes were
      expressed in a wide variety of tissues. These differences in tissue specific
      expression suggest the expression of each ST3Gal influences the distribution of
      sialyl-glycoconjugates in vivo.

PMID- 9184828
TI  - Protein-O-glycosylation in yeast: protein-specific mannosyltransferases.
AB  - S. cerevisiae contains at least six genes (PMT1-6) for dolicholphosphate-D
      mannose: protein-O-D-mannosyltransferases. The in vivo mannosylation of seven O
      mannosylated yeast proteins has been analyzed in a number of pmt mutants. The
      results clearly indicate that the various protein O-mannosyltransferases have
      different specificities for protein substrates. Five of the proteins tested
      (chitinase, a-agglutinin, Kre9p, Bar1p, Pir2p/hsp 150) are mainly
      underglycosylated in pmt1 and pmt2 mutants, whereby qualitative differences exist
      among the various proteins. Two of the O-mannosylated proteins (Ggp1p and Kex2p)
      are not at all affected in pmt1 and pmt2 mutants but are clearly
      underglycosylated when PMT4 is mutated. Although the PMT4 gene product is shown
      to be responsible for O-mannosylating a Ser-rich region of Ggp1p in vivo, a penta
      seryl-peptide is not an in vitro substrate for this transferase. A PMT3 mutation
      does affect O-mannosylation of chitinase only in the genetic background of a
      pmt1pmt2 double mutation, indicating that PMT1 and PMT2 can compensate for a
      deleted PMT3 gene.

PMID- 9184829
TI  - Isolation of new nonconditional Saccharomyces cerevisiae mutants defective in
      asparagine-linked glycosylation.
AB  - We describe the isolation and partial characterization of Saccharomyces
      cerevisiae nonconditional mutants that show defects in N-glycosylation of
      proteins. The selection method is based on the reduction of affinity for the ion
      exchanger QAE-Sephadex as a consequence of the decrease in the negative charge of
      the cell surface. This characteristic reflects a decrease in the incorporation of
      mannosylphosphate units into the N-linked oligosaccharides of the mannoproteins.
      The mutants exhibit low affinity for the basic dye alcian blue and for that
      reason we have called them Idb (low dye binding) mutants. Eight of the
      complementation groups seem to be new as shown by complementation studies with
      previously isolated mutants of similar phenotype. Four of the groups showed a
      significant reduction in the number and/or size of the N-linked oligosaccharides
      attached to secreted invertase. We have analyzed the N-linked oligosaccharides of
      Idb1 and Idb2, the mutants that show the most drastic reduction in the affinity
      for the alcian blue dye. In both cases, the purified endo H-released
      oligosaccharides from the mannoproteins lacked detectable amounts of phosphate
      groups as shown by ion exchange chromatography and the 1H NMR spectra. In
      addition, Ibd1 synthesizes a truncated and unbranched outer chain lacking any
      alpha (1,2) linked mannoses attached to the alpha (1,6) linear backbone.

PMID- 9184830
TI  - Molecular characterization of beta-trace protein in human serum and urine: a
      potential diagnostic marker for renal diseases.
AB  - We have isolated beta-trace protein from cerebrospinal fluid, serum, plasma, and
      urine samples of normal volunteers and sera and hemofiltrate of patients with
      chronic renal failure. Blood-derived and urinary beta-trace have significantly
      higher molecular weights than their cerebrospinal fluid counterpart, the amino
      acid sequences being identical. Oligosaccharide structural analysis revealed
      these molecular weight differences to be due to different N-glycosylation. beta
      Trace from hemofiltrate and urine has larger sugar chains and concurrently
      significantly higher sialylation than cerebrospinal fluid-beta-trace which bears
      truncated "brain-type" oligosaccharide chains (published previously). beta-Trace
      concentrations were about 40 ng/ml for normal sera and plasma. 2000-6000 ng/ml
      were measured in sera of dialysis patients whereas in normal human cerebrospinal
      fluid, beta-trace concentration was about 8000 ng/ml. A reduced amount of 900
      ng/ml was found in a single case of hydrocephalus cerebri. The sialylated
      glycoforms of beta-trace detected in the blood are presumably derived from
      resorbed cerebrospinal fluid protein whereas beta-TP-molecules bearing asialo
      oligosaccharides are absent due to their hepatic clearance. The residual,
      sialylated beta-TP-species are probably eliminated from the blood via the kidney.
      This physiological clearance mechanism for the sialylated glycoforms is disturbed
      in hemodialysis patients resulting in about 100-fold elevated serum
      concentrations. These results let us suggest beta-trace may become a useful novel
      diagnostic protein in renal diseases.

PMID- 9184831
TI  - Expression of beta-galactoside alpha 2,6-sialyltransferase does not alter the
      susceptibility of human colon cancer cells to NK-mediated cell lysis.
AB  - The extent of processing of N-linked oligosaccharides and the sialylation of the
      target cell membranes has been positively correlated with resistance to lysis
      mediated by NK cells, but a conclusive evidence has never been reached. Colon
      cancer tissues express an increased activity of beta-galactoside alpha 2,6
      sialyltransferase (EC 2.4.99.1, alpha 2,6ST), which catalyzed the addition of
      sialic acid in alpha 2,6-linkage to Gal beta 1,4GlcNAc (N-acetyllactosamine)
      sequences of glycoprotein N-linked chains. The resulting increased level of
      membrane alpha 2,6-sialylation appears to be related with a more invasive
      behavior of cancer cells. This phenomenon may depend on a decreased sensitivity
      of colon cancer cells to NK cells. To obtain conclusive evidence on the role
      played by sialylation of N-linked chains in determining the target cell
      susceptibility to NK-mediated lysis, human colon cancer cell lines not expressing
      sialyltransferases acting on N-linked chains were transfected with a rat alpha
      2,6ST cDNA. Stable transfectants expressed different levels of alpha 2,6ST
      activity, were reactive with the Sambucus nigra lectin, specific for alpha 2,6
      linked sialic acid, and compared with control transfectants, showed a remarkable
      decrease in the number of unsubstituted Gal beta 1,4GlcNAc terminal sequences.
      The NK susceptibility of these clones was found to be identical to that of
      control transfectants, either when unstimulated- or IL-2-stimulated lymphocytes
      were used as effectors. Neuraminidase treatment of target cells does not result
      in significant changes to NK susceptibility. Our data demonstrate that sialic
      acid alpha 2,6-linked to N-linked chains of target cell glycoproteins does not
      play a major role in recognition of the target by human NK cells.

PMID- 9184832
TI  - A mathematical model of sialylation of N-linked oligosaccharides in the trans
      Golgi network.
AB  - A mathematical model is developed of the compartmentalized sialylation of N
      linked oligosaccharides in order to understand and predict the outcome of
      sialylation reactions. A set of assumptions are presented, including Michaelis
      Menten-type dependency of reaction rate on the concentration of the glycoprotein
      substrate. The resulting model predicts the heterogeneous outcome of a
      posttranslational oligosaccharide biosynthesis step, a critical aspect that is
      not accounted for in the modeling of the cotranslational attachment of
      oligosaccharides to glycosylation sites (Shelikoff et al., Biotech. Bioeng., 50,
      73-90, 1996) or general models of the secretion process (Noe and Delenick, J.
      Cell Sci., 92, 449-459, 1989). In the steady-state for the likely case where the
      concentration of substrate is much less than the Km of the sialyltransferase, the
      model predicts that the extent of sialylation, x, will depend upon the enzyme
      concentration, enzyme kinetic parameters and substrate residence time in the
      reaction compartment. The value of x predicted by the model using available
      literature data is consistent with the values of x that have been recently
      determined for the glycoproteins CD4 (Spellman et al., Biochemistry, 30, 2395
      2406, 1991) and t-PA (Spellman et al., J. Biol. Chem., 264, 14100-14111, 1989)
      secreted by Chinese hamster ovary cells. For the unsaturated case, the model also
      predicts that x is independent of the concentration of secreted glycoprotein in
      the Golgi. The general modeling approach outlined in this article may be
      applicable to other glycosylation reactions and posttranslational modifications.

PMID- 9184833
TI  - Human medulloblastoma gangliosides.
AB  - To establish a model system for the study of ganglioside metabolism of the human
      brain tumor, medulloblastoma, we have chemically characterized the gangliosides
      of the Daoy cell line. These cells contain a high concentration of gangliosides
      (143 +/- 13 nmol LBSA/10(8) cells). The major species have been structurally
      confirmed to be GM2 (65.9%), GM3 (13.0%), and GD1a (10.3%). Isolation of
      individual gangliosides homogeneous in both carbohydrate and ceramide moieties by
      reversed-phase HPLC and analysis by negative-ion fast atom bombardment
      collisionally activated dissociation tandem mass spectrometry have allowed us to
      unequivocally characterize ceramide structures. In the case of GM2, 10 major
      ceramide subspecies were identified: d18:1-hC16:0, d18:1-C16:0, d18:0-C16:0,
      d18:1-C18:0, d18:1-C20:0, d18:1-C22:0, d18:2-C24:1, d18:1-C23:1, d18:1-C24:1, and
      d18:1-C24:0. Taken together with previous studies, these findings in buman
      medulloblastoma cells support the view that high expression and marked
      heterogeneity of ceramide structure are general characteristics of tumor
      gangliosides, molecules which are shed by the tumor cells and which are
      biologically active in vivo.

PMID- 9184834
TI  - Regulation of chondroitin sulfate biosynthesis by specific sulfation: acceptor
      specificity of serum beta-GalNAc transferase revealed by structurally defined
      oligosaccharides.
AB  - The relationship between sulfation and polymerization in chondroitin sulfate (CS)
      biosynthesis has been poorly understood. In this study, we investigated the
      specificity of bovine serum UDP-GalNAc: CS beta-GalNAc transferase responsible
      for chain elongation using structurally defined acceptor substrates. They
      consisted of tetra- and hexasaccharide-serines that were chemically synthesized
      and various regular oligosaccharides with a GlcA residue at the nonreducing
      terminus, prepared from chondroitin and CS using testicular hyaluronidase. The
      enzyme preparation was obtained from fetal bovine serum by means of heparin
      Sepharose affinity chromatography. The preparation did not contain the alpha
      GalNAc transferase recently demonstrated in fetal bovine serum (Kitagawa et al.,
      J. Biol. Chem., 270, 22190-22195, 1995), that utilizes common acceptor
      substrates. The beta-GalNAc transferase used as acceptors, two hexasaccharide
      serines GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta
      1-O-Ser and GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal (4-sulfate)
      beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, but neither the monosulfated hexasaccharide
      serine GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1
      4Xyl beta 1-O-Ser nor tetrasaccharide-serines with or without a sulfate group at
      C-4 of the third sugar residue Gal-3 from the reducing end. The results indicated
      that the sulfate group at the Gal-3 C-4 markedly affected the transfer of GalNAc
      to the terminal GlcA. In addition, a sulfate group at C-4 of the reducing
      terminal GalNAc of regular tetrasaccharides remarkably enhanced the GalNAc
      transfer, suggesting that the enzyme recognizes up to the fourth saccharide
      residue from the nonreducing end. The level of incorporation into a tetra- or
      hexasaccharide containing a terminal 2-O-sulfated GlcA residue was significant,
      whereas there was no apparent incorporation into tetra- or hexasaccharides
      containing a terminal 3-O-sulfated GlcA or penultimate 4,6-O-disulfated GalNAc
      residue. These results indicated that sulfation reactions play important roles in
      chain elongation and termination.

PMID- 9184835
TI  - The substrate specificity of the snail Lymnaea stagnalis UDP-GlcNAc:GlcNAc beta-R
      beta 4-N-acetylglucosaminyltransferase reveals a novel variant pathway of complex
      type oligosaccharide synthesis.
AB  - UDP-GlcNAc:GlcNAc beta-R beta 1-->4-N-acetylglucosaminyltransferase (beta 4
      GlcNAcT) of the snail Lymnaea stagnalis is an enzyme with structural resemblance
      to mammalian beta 4-galactosyltransferases (beta 4-GalT). The enzyme, which is
      present in the prostate gland of the snail, was expressed in a recombinant form
      in insect cells using the baculovirus technology. This form was used to determine
      the enzyme's in vitro substrate specificity in order to assess its possible role
      in vivo. The enzyme appeared to be a genuine GlcNAcT as no UDP-sugar other than
      UDP-GlcNAc could serve as an efficient donor substrate. Acceptor specificity
      studies showed that the enzyme is far more restricted in acceptor usage than beta
      4-GalT. Oligomers of beta 4-GlcNAc were relatively poor acceptors, indicating
      that this enzyme is not involved in the synthesis of chitin-like molecules. Both
      its polypeptide structure and acceptor specificity suggest that it neither is
      implicated in the synthesis of the chitobiose core of N-linked glycans. Preferred
      substrates are those that contain a beta-GlcNAc residue attached to the carbon-6
      of Gal or GalNAc residues, as found in vertebrate blood-group I-active and O
      linked core 2- and 4-based oligosaccharides, respectively. By contrast, compounds
      in which GlcNAc is beta 6-linked to Man (as in N-linked glycans) are poor
      acceptors. Analysis of the products formed in vitro by 1H-NMR spectroscopy and
      acetolysis showed that the enzyme establishes a GlcNAc beta 1-->4GlcNAc linkage
      and shows branch specificity with a blood-group I-active trisaccharide substrate.
      Furthermore, the enzyme differs from beta 4-GalT in that it is not responsive to
      alpha-lactalbumin. It is proposed that the enzyme functions in a novel, variant
      pathway of complex-type oligosaccharide synthesis in the snail.

PMID- 9184836
TI  - Hydrophobic mannosides act as acceptors for trypanosome alpha
      mannosyltransferases.
AB  - A series of hydrophobic mannosides were synthesized and tested for their ability
      to act as acceptor substrates for mannosyltransferases in a Trypanosoma brucei
      cell-free system. The thiooctyl alpha-mannosides and octyl alpha-mannosides all
      accepted single mannose residues in alpha-linkage, as judged by thin layer
      chromatography of the products before and after jack bean alpha-mannosidase
      digestion. The mannosylation reactions were inhibited by amphomycin, suggesting
      that the immediate donor was dolichol-phosphate-mannose (Dol-P-Man) in all cases.
      The transferred alpha-mannose residues were shown to be both alpha 1-2 and alpha
      1-6 linked by Aspergillus phoenicis alpha-mannosidase and acetolysis treatments,
      respectively. These data suggest that the compounds can act as acceptor
      substrates for the Dol-P-Man dependent alpha 1-2 and alpha 1-6
      mannosyltransferases of the GPI biosynthetic pathway and/or the dolichol-cycle of
      protein N-glycosylation. One of the compounds, Man alpha 1-6 Man alpha 1-O
      (CH2)7CH3, inhibited endogenous GPI biosynthesis in the cell-free system,
      suggesting that it could be a substrate for the trypanosome Dol-P-Man:Man2GlcN-Pl
      alpha 1-2 mannosyltransferase.

PMID- 9184837
TI  - Stereoselectivity of the Chinese hamster ovary cell sialidase: sialoside
      hydrolysis with overall retention of configuration.
AB  - The stereochemical course of enzymatic hydrolysis by the soluble sialidase from
      Chinese hamster ovary cells, expressed as a recombinant protein in insect Sf9
      cells, was determined using proton nuclear magnetic resonance spectroscopy. 4
      Methyl umbelliferyl-N-acetyl neuraminic acid was employed as substrate, and the
      stereoselectivity of the enzyme catalysis was ascertained by monitoring the H3
      axial and equatorial protons of the sialic acid product over the reaction course.
      At both high (3 U) and low concentrations (1 U) of the enzyme, the alpha anomer
      of the sialic acid was clearly observed as the initial reaction product. The
      corresponding beta anomer of sialic acid appeared much later in the reaction,
      arising from mutarotation of the alpha anomer. Similar studies were also carried
      out using the Salmonella typhimurium LT 2 sialidase, a protein of similar size
      and substrate specificity. Both enzymes apparently cleave the alpha linked
      sialoside substrate with retention of configuration. Based on the observations of
      a wide variety of other glycohydrolytic enzymes that have shown a strong
      correlation of the stereoselectivity of catalysis with active site topology
      (Gebler et al., J. Biol. Chem. 267, 12559-12561, 1992), the results obtained here
      suggest that the microbial and mammalian sialidases have a homologous active site
      architecture even though the molecules do not share significant primary sequence
      similarities.

PMID- 9184838
TI  - Structural and biological roles of glycosylations in pulmonary angiotensin I
      converting enzyme.
AB  - We enzymatically deglycosylated pig lung angiotensin I-converting enzyme (ACE) to
      study the involvement of its glycanic chains in its physicochemical and catalytic
      properties. The effects of endoglycosidases F2 and H, and of N-glycanase were
      assessed by ACE mobility in SDS-PAGE. N-Glycanase only was completely effective
      with or without previous denaturation, leading to a shift in ACE M(r) from 172 to
      135 kDa; endoglycosidase F2 produced the same shift but only without previous
      denaturation. Deglycosylated ACE had the same kcat as native ACE for the
      substrate hippuryl-histidyl-leucine, and an identical Stokes radius as measured
      by size-exclusion high performance liquid chromatography. Neuraminidase had no
      effect on ACE Stokes radius but slightly decreased its kcat which could be
      related to variations in ionization of the active site. The isoelectric point of
      ACE, as, determined by isoelectric focusing, increased from 4.5-4.8 to 5.0-5.3
      after either endoglycosidase F2 or neuraminidase digestion, but still with
      microheterogeneities which thus did not seem to be related to ACE glycans.
      Deglycosylated ACE did not bind onto agaroselectins in contrast to native ACE
      which bound strongly to concanavalin A showing interactions involving
      oligomannosidic or biantennary and sialylated N-acetyl-lactosaminic isoglycans.
      Finally, tunicamycin, an inhibitor of N-glycosylation, did not modify ACE
      secretion by endothelial cells. Thus, ACE glycans have no drastic effects on
      structural and biological properties of the protein, but they may have a
      functional role on intracellular targeting of both secreted and membrane-bound
      ACE isoforms, also for the protection of the soluble plasma form against hepatic
      lectins and the maintenance of its hydrosolubility.

PMID- 9184839
TI  - Purification of rabbit skeletal muscle proteoglycogen: studies on the
      glucosyltransferase activity of polysaccharide-free and -bound glycogenin.
AB  - Proteoglycogen is the end product in the process of glycogen biogenesis. We have
      purified rabbit muscle proteoglycogen and studied the glucosyltransferase
      reactions catalyzed by its protein moiety, glycogenin, free or bound to the
      polysaccharide. The purification strategy involved dissolution of proteoglycogen
      and cosedimenting membrane vesicles in a Triton X-114/Triton X-45 mixture
      followed by partition in the aqueous phase, potassium iodide precipitation of
      accompanying proteins, and washing by high-speed centrifugation. Glycogenin or a
      proteoglycogen species of an average molecular mass of 200 kDa was isolated by
      ion-exchange chromatography after the purified proteoglycogen had been subjected
      to long or short amylolytic digestion, respectively. Besides autoglucosylation
      from UDP-glucose, glycogenin was capable of autogalactosylation from UDP
      galactose. The autoglucosylation reaction was not inhibited by the simultaneous
      glucosylation of the exogenous acceptors N-(maltosyl-alpha-1-4-(1-deoxiglucitol))
      peptide or n-dodecyl-beta-D-maltoside. The polysaccharide-bound glycogenin
      species of 200 kDa showed to be active for the glucosylation of exogenous
      acceptor and represented the isolated proteoglycogen of higher size having
      glucosyl transferase activity. This is the first description of the isolation of
      native proteoglycogen and a proteoglycogen species having glucosyltransferase
      activity.

PMID- 9184840
TI  - Phylogenetic survey of endomannosidase indicates late evolutionary appearance of
      this N-linked oligosaccharide processing enzyme.
AB  - Endo-alpha-D-mannosidase is a processing enzyme which in contrast to other
      glycosidases involved in the trimming of N-linked oligosaccharides of
      glycoproteins acts at an internal position by cleaving the linkage between the
      glucose-substituted mannose and the internal portion of the polymannose unit and
      thereby provides an alternate deglucosylating pathway. In order to evaluate at
      what stage in evolution this unusual enzyme first emerged, we have carried out a
      phylogenetic survey of its distribution among a broad group of eukaryotes ranging
      from unicellular organisms to highly developed animals and plants, all of which
      are known to have the capacity to N-glycosylate proteins and subsequently trim
      the nascent glucosylated polymannose oligosaccharides. It became evident from
      enzyme assays and in vivo studies that endomannosidase is limited in its
      distribution to members of the chordate phylum, including placental and marsupial
      mammals, birds, reptiles, amphibians, and fish, with the single except of the
      Mollusca in which it was detected in three distinct classes. The enzyme's absence
      in all other invertebrates examined as well as in yeast, various protozoa and
      higher plants, stands in contrast to glucosidase II and alpha 1,2-mannosidase
      which were found to be present in all eukaryotes studied. The observation that
      endomannosidase activity was not present in insects was confirmed by
      radiolabeling experiments with Sf9 cells in culture. These cells, which are
      widely employed for the expression of mammalian genes, were in distinction to
      mouse cells unable to circumvent a castanospermine (CST)-induced glucosidase
      blockade. Moreover we observed that Tetrahymenae, which synthesize glycoproteins
      with truncated N-linked oligosaccharides, could not process these beyond the
      Glc3Man5GlcNAc2 stage in the presence of CST. The late appearance of
      endomannosidase during evolution suggests a need for an alternate deglucosylation
      route in higher animals which parallels the development of elaborate complex N
      linked oligosaccharides. Such carbohydrate units are believed to carry out vital
      biological functions and deglucosylation is a prerequisite to the further
      processing steps required for their formation.

PMID- 9184841
TI  - Immunohistochemical expression of glucose transporter-1 in human penile
      proliferative lesions.
AB  - Glucose transporters (GLUTs) are a family of membrane proteins responsible for
      the transport of glucose across cellular membranes. In terms of their mRNA
      levels, they have been reported to be expressed in some human tumours. However,
      the immunohistochemical localization of GLUTs in human urogenital lesions has
      rarely been studied. This study was performed to evaluate the expression of GLUT1
      in penile proliferative lesions (18 cases of penile carcinoma and 13 cases of
      condyloma acuminatum). Using an isoform-specific anti-GLUT1 antibody, formalin
      fixed paraffin-embedded sections were stained by the avidin-biotin complex
      method. In all cases of penile carcinoma, GLUT1 staining was diffusely recognized
      on the cell membrane of the carcinoma cells in the mainly infiltrating areas.
      However, the inner areas of the tumour were more weakly and focally stained. The
      intensity of staining for the penile carcinoma (staining score = 2.8 +/- 0.6) was
      stronger than that for condyloma acuminatum and that for adjacent non
      proliferative areas. All cases of condyloma acuminatum showed a diffuse staining
      on the cell membrane in the basal and intermediate layers (staining score = 2.4
      +/- 0.5). Non-proliferative (histologically normal) glans areas adjacent to the
      above lesions expressed the weakest GLUT1 staining only in the stratum basale
      (staining score = 1.8 +/- 0.5). These three areas showed significantly different
      staining scores from each other (p < 0.01). In conclusion, GLUT1 is expressed
      dominantly in penile proliferative lesions, especially in infiltrating areas of
      penile carcinoma.

PMID- 9184842
TI  - Effect of sympathectomy on the phenotype of smooth muscle cells of middle
      cerebral and ear arteries of hyperlipidaemic rabbits.
AB  - This study was carried out to determine whether sympathectomy influences the
      phenotypic modulation of smooth muscle cells in the peripheral and cerebral
      arteries of heritable hyperlipidaemic rabbits. Unilateral superior cervical
      ganglionectomy (common origin of innervation to the middle cerebral artery and
      the central ear artery) was performed on four Watanabe heritable hyperlipidaemic
      rabbits. Cross-sections of the ipsi- (sympathectomized) and the contralateral
      (intact) cerebral and ear arteries were prepared 2 months later and labelled with
      monoclonal antibodies against vimentin and desmin, two markers of the
      differentiation of smooth muscle cells, and alpha-smooth muscle actin, a marker
      of these cells. Sections from control and sympathectomized arteries were analysed
      with a confocal laser scanning microscope. Compared with contralateral intact ear
      arteries, the sympathectomized ear artery developed a thickened intima with
      dedifferentiated smooth muscle cells, expressing alpha-smooth muscle actin but no
      desmin, whereas the middle cerebral artery remained unchanged. These results
      suggest that sympathectomy may favour the progression of atherosclerosis in
      peripheral but not in cerebral arteries of Watanabe heritable hyperlipidaemic
      rabbits.

PMID- 9184843
TI  - In situ detection of constitutive superoxide anion production in granules of mast
      cells.
AB  - 3,3'-Diaminobenzidine, in the presence of manganese and cobalt ions, was applied
      for the detection of superoxide anions in unfixed cryostat sections of rat
      oesophagus, trachea, skin and intact mesenterium. In all connective tissues, a
      blue final reaction product was found in a granular form in mast cells. The
      amount of final reaction product formed after incubation with diaminobenzidine
      and cobalt ions was increased by the addition of manganese ions. Electron
      microscopical analysis revealed that the electron-dense final reaction product
      was exclusively present in the granules of mast cells and on elastin fibres. It
      was found that the constitutive spontaneous formation of final reaction product
      in mast cells was enzymatic and dependent on the presence of oxygen in the
      medium. Of all the enzyme inhibitors and free radical scavengers tested, only
      azide strongly reduced the amount of final reaction product. It was concluded
      that the reaction was partly caused by peroxidase activity, but that superoxide
      anions are also constitutively and spontaneously produced in mast cell granules.
      The exact enzymatic source could not be established. Whether this property of
      mast cell granules plays an antimicrobial role in connective tissues can only be
      speculated.

PMID- 9184844
TI  - Immunohistochemical identification and comparison of glial cell lineage in
      foetal, neonatal, adult and neoplastic human adrenal medulla.
AB  - The differentiation of glial cells in developing, neonatal, adult and neoplastic
      human adrenal medulla has studied immunohistochemically. From 8 to 28 weeks'
      gestational age, S-100 protein and its beta-subunit revealed two different glial
      cell populations in adrenal glands, namely Schwann-like and sustentacular cells.
      Schwann-like cells were spindle-shaped cells forming a continuous layer around
      groups of sympathetic neuroblasts, often in contact with Schwann cells of nerve
      fibres entering neuroblastic groups. Sustentacular cells were round or oval cells
      with dendritic cytoplasmic processes; they were not associated with nerve fibres
      and mingled both with sympathetic neuroblasts and differentiating chromaffin
      cells. The developmental fate of Schwann-like cells was different from that of
      sustentacular cells. Schwann-like cells disappeared from the 28th week of
      gestational age, in association with the disappearance of sympathetic
      neuroblastic groups, and they were rarely found in neonatal and adult adrenal
      medulla. In contrast, sustentacular cells persisted between medullary chromaffin
      cells, and their number and dendritic cytoplasmic processes progressively
      increased from foetus to adult. In eight cases of primitive adrenal neuroblastic
      tumours of neonatal age (five undifferentiated neuroblastomas and three
      ganglioneuroblastomas), Schwann-like cells were found at the periphery of tumoral
      nests with a lobular growth pattern, while rare sustentacular cells were
      associated with neuroblasts. In two cases of adult phaeochromocytomas, only
      sustentacular cells were detected between chromaffin tumoral cells. Our findings
      suggest that the glial cell types and their distribution in primitive adrenal
      medulla tumours closely resemble those observed during development in the groups
      of adrenal sympathetic neuroblasts and in the clusters of chromaffin cells.

PMID- 9184845
TI  - Immunocytochemical identification of metallothionein-positive cells in rheumatoid
      synovium and analysis of their cell lineage.
AB  - Metallothionein is a ubiquitous low molecular weight metalloprotein with powerful
      protective properties against oxygen radical-mediated cytotoxicity associated
      with inflammatory processes. In rheumatoid arthritis, the inflammatory damage to
      the synovium appears to be mediated by free radicals released by the high
      concentration of neutrophils found in the synovial fluid of the inflamed joint.
      Synovial tissue obtained during routine surgery on rheumatoid and non-rheumatoid
      joints was subjected to an indirect immunoperoxidase protocol for the
      immunolocalization of metallothionein using mouse monoclonal anti-metallothionein
      antibody E9, reactive against the two major isoforms of mammalian
      metallothionein. A layer of large dendritic-like cells situated subsynovially in
      the rheumatoid synovium stained very positively for the metalloprotein, both
      cytoplasmically and in their nuclei. These cells were not found in non-rheumatoid
      osteoarthritic or in undamaged synovial tissue associated with traumatic joint
      injury. An attempt was made to investigate their lineage using a series of
      antibody markers against epithelial cells, endothelial cells, smooth muscle,
      mesothelial cells, fibroblasts, neutrophils, dermal dendrocytes, macrophages, low
      and high molecular weight cytokeratin as well as a cell proliferation marker.
      From our results, it is suggested that these metallothionein-positive cells are
      probably myofibroblasts similar to the highly motile cells present in granulation
      tissue. They may originate from perivascular areas of synovium and their movement
      into the inflamed synovium may reflect the cytoprotective role of metallothionein
      acting as a free radical scavenger against oxidative damage.

PMID- 9184846
TI  - The effect of verapamil on mitochondrial calcium content in normoxic, hypoxic and
      reoxygenated rat liver.
AB  - Calcium channel blockers protect cells against ischaemia-reperfusion injury. In
      the present study, the effect of verapamil on mitochondrial calcium content was
      investigated in situ in normoxic, hypoxic and reoxygenated rat liver. Subcellular
      distribution of exchangeable calcium ions, which form an electron-dense
      precipitate with antimonate, was demonstrated with the glutaraldehyde-osmium
      antimonate technique. Calcium precipitates were quantified morphometrically using
      automatic image analysis. In normoxic liver, the mitochondrial calcium content
      formed a gradient decreasing from the periportal to perivenous regions. The low
      mitochondrial calcium content in perivenous regions remained unaffected in all
      experimental conditions. In hypoxic and reoxygenated liver, the calcium content
      in mitochondria of the periportal areas was significantly reduced. Verapamil
      pretreatment levelled the calcium gradient in normoxic liver by reducing the
      periportal calcium content. Verapamil had no effect on the mitochondrial calcium
      content in hypoxic liver. In contrast, in verapamil-pretreated reoxygenated
      liver, the mitochondrial calcium content in periportal mitochondria increased
      significantly, thus restoring the zonal calcium gradient. In conclusion, these
      data suggest that modulations of mitochondrial calcium content in the periportal
      region of the liver lobule may play an important role in the protective effects
      of verapamil against ischaemia-reperfusion injury.

PMID- 9184847
TI  - Specimen preparation and quantification of collagen birefringence in unstained
      sections of articular cartilage using image analysis and polarizing light
      microscopy.
AB  - To establish an optimal method for analysis of the collagen structures from
      unstained tissue sections, a computerized image analysis system using a charge
      coupled device camera coupled to a polarizing light microscope was used.
      Retardation values of birefringence, which are proportional to the content and
      fibril orientation of collagen in the extracellular matrix of articular
      cartilage, were determined from sections prepared in different ways. In the
      superficial zone of articular cartilage, the highest retardation values were
      recorded from sections cut parallel to the so-called split lines indicating the
      anisotropic arrangement of collagen. Complete digestion of glycosaminoglycans
      reduced the retardation value by approximately 6.0%, suggesting a minor, but not
      insignificant, contribution of glycosaminoglycans to the birefringence of the
      matrix. The use of a mounting medium with a refractive index close to that of the
      collagen (e.g. DPX) increased the specificity of the method, since the optical
      anisotropy of collagen derives predominantly from the intrinsic (structural)
      birefringence. In conclusion, analysis of unstained sections after careful
      removal of paraffin and glycosaminoglycans from the tissues provides a sensitive
      and rapid quantitative assessment of oriented collagen structures in articular
      cartilage.

PMID- 9184848
TI  - Natriuretic peptide immunoreactivity in nerve structures and Purkinje fibres of
      human, pig and sheep hearts.
AB  - Atrial natriuretic peptide is a well-described peptide in cardiac Purkinje fibres
      and has been shown to interfere with the autonomic regulation in the heart of
      various species, including man. Recently, we detected immunoreactivity for the
      peptide in intracardial ganglionic cells and nerve fibre varicosities of bovine
      hearts, by the use of a modified immunostaining technique that induced an
      improved detection of natriuretic peptides. These findings raised the question as
      to whether natriuretic peptides are detectable in these tissues in man and other
      species. The conduction system from human, pig and sheep hearts was dissected
      processed with antisera against atrial natriuretic peptide and the closely
      related brain natriuretic peptide. Immunostaining for the brain natriuretic
      peptide was detected in some Purkinje fibres in all of these species.
      Interestingly, in pig, sheep and human hearts, some ganglionic cells and nerve
      fibres showed atrial natriuretic peptide immunoreactivity, particularly in the
      soma of human ganglionic cells. This is the first study showing immunoreactivity
      for the atrial natriuretic peptide in nerve structures and for the brain
      natriuretic peptide in Purkinje fibres of the human heart. The results give a
      morphological correlate for the documented effects of atrial natriuretic peptide
      on the heart autonomic nervous system and for the presumable effects of brain
      natriuretic peptide in the conduction system of man.

PMID- 9184849
TI  - Changes in the distribution of integrins and their basement membrane ligands
      during development of human thyroid follicular epithelium.
AB  - Interactions between cells and basement membrane components are crucial for the
      regulation of epithelial cell differentiation and polarization. We have studied
      by immunohistochemical methods the distribution of integrin adhesion proteins and
      some of their basement membrane ligands in foetal (16-19 weeks) and adult thyroid
      follicular epithelia. A diffuse immunoreactivity for only alpha 3, alpha v and
      beta 1 integrins was found in foetal follicular epithelium, whereas in adult
      follicular epithelium these integrins were expressed basally in a polarized
      manner. Additionally, beta 3 integrin was seen in a more basolaterally confined
      manner in adult follicular epithelium. Among basement membrane components,
      laminin alpha 1, beta 1, gamma 1 and beta 2 chains were found in epithelial
      basement membranes of the foetal thyroid gland, suggestive of the presence of
      laminins-1 and -3. In contrast, the basement membranes of adult follicular
      epithelium presented a much weaker immunoreactivity for the laminin beta 2 chain.
      Furthermore, immunoreactivity for the laminin alpha 2 chain was occasionally seen
      in adult thyroid glands, apparently confined to myofibroblasts. Immunoreactivity
      for type IV collagen alpha 1 and alpha 2 (IV) chains was found in follicular
      basement membranes of foetal as well as adult thyroid gland. The results suggest
      that during maturation of foetal thyroid follicular epithelium a distinct
      polarization of integrins takes place. In mature thyroid follicular epithelium,
      the presumable adhesion-mediating integrin complexes are alpha 3 beta 1, alpha v
      beta 1 and/or alpha v beta 3 mediating adhesion to laminin-1 (alpha 1-beta 1
      gamma 1) and type IV collagen trimer alpha 1(2) alpha 2 (IV).

PMID- 9184850
TI  - Basic strategies for valid cytometry using image analysis.
AB  - The present review provides a starting point for setting up an image analysis
      system for quantitative densitometry and absorbance or fluorescence measurements
      in cell preparations, tissue sections or gels. Guidelines for instrumental
      settings that are essential for the valid application of image analysis in
      cytophotometry and cytofluorometry are described. The general principles of the
      working mechanism of CCD cameras in combination with general methods to improve
      the behaviour of the cameras are presented. Optimization of illumination of
      microscopical and macroscopical objects receives special attention because of its
      importance for valid cytometry. Sources of errors in quantitative measurements
      are listed and step-by-step charts for tuning the CCD camera, frame grabber and
      illumination for the optimal use of the systems are described. Suggestions are
      given for improvement of image arithmetic in difficult imaging situations, such
      as low fluorescence signals and high absorbance signals.

PMID- 9184851
TI  - Autophagic proteolysis: control and specificity.
AB  - The rate of proteolysis is an important determinant of the intracellular protein
      content. Part of the degradation of intracellular proteins occurs in the
      lysosomes and is mediated by macroautophagy. In liver, macroautophagy is very
      active and almost completely accounts for starvation-induced proteolysis. Factors
      inhibiting this process include amino acids, cell swelling and insulin. In the
      mechanisms controlling macroautophagy, protein phosphorylation plays an important
      role. Activation of a signal transduction pathway, ultimately leading to
      phosphorylation of ribosomal protein S6, accompanies inhibition of
      macroautophagy. Components of this pathway may include a heterotrimeric Gi3
      protein, phosphatidylinositol 3-kinase and p70S6 kinase. Recent evidence
      indicates that lysosomal protein degradation can be selective and occurs via
      ubiquitin-dependent and -independent pathways.

PMID- 9184852
TI  - Microwave incubation improves lipolytic enzyme preservation for ultrastructural
      cytochemistry.
AB  - Standard methods for the ultrastructural detection of lipase and sphingomyelinase
      activities in the skin result in considerable loss of structural preservation,
      often interfering with accurate delineation of enzyme localization in association
      with specific organelles. Moreover, poor preservation occurs, even after
      extensive aldehyde prefixation, owing to the prolonged incubation times needed to
      detect residual enzyme activity, which often require non-physiological
      conditions. A modified incubation protocol is described here, which uses
      microwave irradiation in conjunction with drastically shortened incubation times,
      resulting in both superior ultrastructural preservation and excellent
      localization in mammalian epidermis. This method should be useful generally not
      only for the study of lipase localization in skin, but also in conjunction with
      the cytochemical detection of a variety of enzymes in various types of tissue.

PMID- 9184853
TI  - Immunophenotyping of human HT29 colon cancer cell primary tumours and their
      metastases in severe combined immunodeficient mice.
AB  - The immunophenotype of HT29 human colon cancer cells implanted into severe
      combined immunodeficient mice was assessed in primary tumours and their
      metastases in the lungs using an indirect immunohistochemical method. After
      primary tumours were surgically removed, the metastases were given time to
      develop, thus paralleling the clinical situation. While vimentin was negative in
      both primary and secondary tumours, E-cadherin was present as membrane-bound
      labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and
      CEA were consistently positive in both primary and metastatic tumours, CD44
      variant 6 and CA125 were negative in metastases but positive in the primary
      tumours. There was a significant increase in the percentage of cells labelled for
      p53 in the primary tumours compared with the metastases. For the proliferation
      markers, there was no significant difference in labelling between primary tumours
      and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest
      and most consistent reaction in both primary and secondary tumours. The results
      indicate that, for certain immunohistochemical markers, results are the same in
      both primary tumours and metastases. Hence, in these cases, antigens that are
      expressed on the primary tumour as well as on the metastases can serve as target
      molecules for immunologically based forms of treatment of metastases.

PMID- 9184854
TI  - Gene expression of matrix metalloproteinase-1 (interstitial collagenase) and
      matrix metalloproteinase-3 (stromelysin-1) in basal cell carcinoma by in situ
      hybridization using chondroitin ABC lyase.
AB  - The gene expression of matrix metalloproteinase-1 and -3 was examined in basal
      cell carcinomas by in situ hybridization using digoxigenin-labelled riboprobes.
      Nodulo-ulcerative basal cell carcinomas demonstrated the gene expression for both
      metalloproteinases but superficial basal cell carcinomas did not present any
      transcripts for them. Transcripts for matrix metalloproteinase-1 (interstitial
      collagenase) were demonstrated densely in stromal cells among tumour masses, and
      those for matrix metalloproteinase-3 (stromelysin-1) were detected only in more
      advanced cases. Neither were expressed in tumour cells. The two
      metalloproteinases were produced by stromal cells according to the tumour
      invasion process, in which various growth factors, cytokines and inflammatory
      factors, which could regulate gene expressions of matrix metalloproteinases, were
      involved. It was also found that hybridization signals were enhanced by treatment
      with chondroitin ABC lyase, which digested abundant glycosaminoglycans in basal
      cell carcinoma. The procedure for the digestion is simple, and appears to be of
      value for in situ hybridization studies on tissues containing large amounts of
      glycosaminoglycans.

PMID- 9184855
TI  - Cytokeratin demonstration in thick breast tissue slices.
AB  - Tissue slices (500 to 1000 microns thick) of archival formalin-fixed, paraffin
      embedded breast tissue were immunostained by a cytokeratin antibody (MNF116)
      using a streptavidin-biotin complex procedure. The technique requires prolonged
      exposure of tissue slices to the reagents. Use of the detergent Triton X-100
      facilitated penetration of high molecular weight reagents through the tissue
      slices. Fifty of 58 slices 500 microns thick (86%) showed good to excellent
      immunostaining, and 13 of 20 slices 1000 microns thick (65%) showed similar
      staining. Omission of the primary antibody eliminated any immunostaining.
      Comparison with corresponding Haematoxylin staining of the thick slices (the
      conventional procedure for such breast tissue slices) showed that thick-slice
      cytokeratin immunostaining markedly improved visualization of the epithelial
      structure in normal lobules and invasive carcinomas. Although the
      immunohistochemical technique takes 33 days for completion, the quality of the
      epithelial images outweighs this disadvantage.

PMID- 9184856
TI  - Simultaneous in situ hybridization and TUNEL to identify cells undergoing
      apoptosis.
AB  - Apoptotic cells in tissue sections can be localized by in situ labelling of
      partly degraded DNA. In a heterogeneous population of cells, however, the
      specific identity of cell types undergoing apoptosis often cannot be reliably
      achieved at the light microscope level because of the marked alterations in
      cellular morphology that characterize apoptosis. In order to clearly specify cell
      types undergoing apoptosis, in situ end labelling has been coupled to
      immunohistochemistry. This method is limited by the availability of antibodies
      that bind to cell-specific protein markers in tissue sections. In contrast, we
      describe a method that combines in situ end labellin with in situ hybridization,
      a technique that specifies cell types based on mRNA expression. Taking advantage
      of the specific expression of surfactant protein C mRNA in type II alveolar
      epithelial cells, we demonstrate that this technique has the ability to localize
      alveolar type II cells undergoing apoptosis in vivo after the intratracheal
      instillation of an antibody that activates the cell surface Fas protein. The wide
      availability of cell-specific gene markers suggests that this method can be
      adapted to define cell types that undergo apoptosis during various physiological
      and pathological states in vivo.

PMID- 9184857
TI  - Binding of antibodies against high and low molecular weight cytokeratin proteins
      in the human placenta with special reference to infarcts, proliferation and
      differentiation processes.
AB  - Recent immunocytochemical studies have shown that placental villous trophoblasts
      contain the high molecular weight cytokeratin (CK) proteins 5/6 and 17. In the
      case of CK 17, trophoblastic immunostaining was positive in villi covered by
      fibrinoid. CKs 5/6 and 17 are expressed by hyperproliferative cells. The aim of
      this investigation was to examine the location of these CKs in placental
      infarcts, known to be demarcated by fibrinoid and hyperproliferative
      trophoblasts. The results were compared with those obtained by immunostaining
      against Ki-67, tenascin and alpha 1-, alpha 6- and beta 1-integrins, which are
      involved in cell proliferation, differentiation and regenerative processes.
      Furthermore, the expression of the single CKs 7, 8, 10, 13, 14, 18 and 19 was
      investigated by immunocytochemistry and immunoblotting. While low and high
      molecular weight CKs were present in villous and extravillous trophoblasts, only
      low molecular weight CKs were detected in vascular and extravascular placental
      smooth muscle cells. Placental infarcts revealed different immunoreactivities in
      the infarct margin and centre: high molecular CKs, tenascin, Ki-67 and oncofoetal
      fibronectin predominated in the infarct margin, low molecular CKs, fibrin and
      integrins in the centre. The expression of tenascin and a defined change in the
      expression of CK 17 indicates villous repair and hyperproliferative mechanisms in
      placental infarcts.

PMID- 9184858
TI  - Efficacy of intra-arterial norcantharidin in suppressing tumour 14C-labelled
      glucose oxidative metabolism in rat Morris hepatoma.
AB  - Norcantharidin is the demethylated form of Cantharidin, which is the active
      ingredient of the blister beetle, Mylabris, a long used Chinese traditional
      medicine. Though not well publicized outside China, Norcantharidin is known to
      possess significant anti-hepatoma activity, and is relatively free from side
      effects. In the present study, glucose oxidation in tumour and liver tissue
      slices harvested from hepatoma-bearing animals was quantified by measuring the
      radioactivity of 14C-labelled CO2 released from 14C-glucose in oxygen-enriched
      incubation medium. Results were expressed as a tumour/liver ratio. For
      comparison, treatments with Norcantharidin, Adriamycin and with hepatic artery
      ligation were studied. The mean tumour/liver ratio was 4.2 +/- 2.2 in untreated
      controls, but dropped significantly to 2.3 +/- 0.5 (p < 0.05) with intra-arterial
      Norcantharidin (0.5 mg/kg) and to 2.3 +/- 0.7 (p < 0.05) with intra-arterial
      Adriamycin (2.4 mg/kg), and to 2.2 +/- 0.7 (p < 0.05) with hepatic artery
      ligation. However, with intravenous Adriamycin at 2.4 mg/kg, the mean
      tumour/liver ratio was reduced to only 3.5 +/- 2.0 and was not significantly
      different from untreated controls. It is concluded that intra-arterial
      Norcantharidin is as effective as intraarterial Adriamycin and hepatic artery
      ligation in suppressing tumour glucose oxidative metabolism. These result simply
      that Norcantharidin may have a role to play in the chemotherapy of primary liver
      cancer.

PMID- 9184859
TI  - The ability of bile to scavenge superoxide radicals and pigment gallstone
      formation in guinea pigs.
AB  - After partial ligation of the common bile duct (CBD) of guinea pigs, 14 of 16
      animals developed pigment gallstones within one week (S group). Intraperitoneal
      injection of Vit. E and C, each 10 mg/kg daily from 3 days before CBD ligation to
      one week after the operation (S+V group), decreased the gallstone incidence to
      5/14 (exact probability < 0.01). The gallstone incidence in the control group,
      that only received laparotomy without ligation of the CBD, was 0/15. Biochemical
      analysis of the gallbladder bile showed that stricture of the CBD was associated
      with a significant increase in levels of unconjugated bilirubin (UCB) and Ca2+ (p
      < 0.05 and < 0.01). Simultaneously the scavenging rate (SR) of superoxide radical
      in bile significantly decreased (p < 0.05). Comparing S+V group with S group, the
      effect of Vit. E and C on the concentrations of UCB and Ca2+ in bile was not
      significant (both p > 0.05), but Vit. E and C normalized the SR, and the
      difference between S group and S+V group was significant (p < 0.05). These
      results suggested that Vit. E and C, known as antioxidants, enhanced the ability
      to scavenge oxygen radical in S+V group; and that in addition to the increases of
      UCB and Ca2+ concentrations, the participation of oxygen radicals might be of
      importance for pigment gallstone formation induced by bile duct obstruction.

PMID- 9184860
TI  - Laparoscopic cholecystectomy in cirrhotic patient.
AB  - Cholecystectomy is associated with increased risk in patients with liver
      cirrhosis. Moreover, cirrhosis and portal hypertension have been considered
      relative or absolute contraindication to laparoscopic cholecystectomy. As
      experience with laparoscopic cholecystectomy increased, we decided to treat
      cirrhotic patients via this approach. Between January 1994 and April 1995, nine
      patients with a Child-Pugh's stage A cirrhosis underwent elective laparoscopic
      cholecystectomy with intraoperative cholangiography. There was no significant per
      or post-operative bleeding and no blood transfusion was necessary. There was no
      mortality and very low morbidity. Median hospital stay was 3 days. This series
      suggests that well-compensated cirrhosis can not be considered a contraindication
      to laparoscopic cholecystectomy.

PMID- 9184861
TI  - Long-term results of longitudinal pancreatico-jejunostomy for chronic pancreatic
      pain.

PMID- 9184862
TI  - Laparoscopic vs open ultrasound of the liver: an in vitro study.
AB  - Intra-operative contact ultrasound is a sensitive method of detecting liver
      tumours. The aim of this study was to compare the sensitivity of open contact
      ultrasound (OUS) of the liver with laparoscopic contact ultrasound (LUS).
      Hypoechoic "lesions" were created in 5 fresh pig livers by inserting 28 grapes
      via small incisions in the inferior surface. The size (range 8-25 mm) and
      location of each grape was recorded. Scanning was undertaken in random order by
      two experienced independent observers with no knowledge of the size, number or
      position of the lesions, using an Aloka 650 series scanner and 7.5 MHz probes.
      The crude sensitivity with OUS was 96% and 100% respectively for the two
      observers, and 92% for each with LUS. One grape was interpreted as 2 separate
      grapes on LUS by one observer. Absolute sensitivity (grapes identified in the
      correct location) was 86% and 93% respectively with OUS and 79% for each observer
      with LUS. LUS was almost as sensitive as OUS in this model of hepatic metastases.

PMID- 9184863
TI  - Cystic dilatations of the common bile duct in adults.
AB  - Cystic dilatations of the common bile duct are believed to be of congenital
      etiology with most cases presenting in childhood. During the last 20 years, 10
      patients with cystic dilatations of the bile duct were treated in our Department.
      There were 5 men and 5 women with an age range of 35-81 years. Clinical
      presentation consisted of right hypohondrial pain, nausea, vomiting and a history
      of obstructive jaundice. Diagnosis was established by ultrasound, cholangiography
      and ERCP in most cases. According to the Todani classification system, 5 patients
      had type I cysts, 4 had type II and one had type III. At the time of surgery,
      main associated diseases were choledocholithiasis in 3 cases and cholangitis in 2
      cases. One patient (type III) underwent endoscopic sphincterotomy; 4 patients
      underwent internal drainage and 2 of them developed mild cholangitis
      postoperatively; 5 patients underwent excision of the cyst and a biliary-enteric
      bypass and developed no main complications. Patients remained in good health
      during long-term follow-up. We conclude that cyst excision is the treatment of
      choice for adults in order to reduce postoperative morbidity and the potential
      risk of malignancy.

PMID- 9184864
TI  - Pathologic and radiographic studies of intrahepatic metastasis in hepatocellular
      carcinoma; the role of efferent vessels.
AB  - The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and
      pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet
      been clarified. Three hundred ninety-three resected specimens of HCC were
      examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors
      < or = 5 cm in diameter were examined for the relationship between mode of tumor
      spread and tumor size. Efferent vessels in HCC were identified by direct
      injection of radiopaque material into the tumor in 23 resected liver specimens
      and by percutaneous infusion of radiopaque media into tumor nodules in 8
      patients. The mode of tumor spread in HCC progressed from capsular invasion to
      extracapsular invasion, then to vascular invasion, and finally to intrahepatic
      metastasis. There was a strong statistical correlation between the presence of
      intrahepatic metastasis and portal vein thrombosis (p < 0.05, R = 0.998).
      Radiopaque material injected directly into 23 resected tumors entered only the
      portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors.
      In all 8 patients with unresectable lesions, radiopaque media injected
      percutaneously into tumor nodules flowed only into the portal vein. These
      findings suggest that intrahepatic invasion by HCC may occur through the portal
      vein as an efferent tumor vessel.

PMID- 9184866
TI  - A different method of hepaticojejunostomy for proximal biliary injuries.
AB  - The management of proximal biliary injuries presents a surgical challenge.
      Anastomoses can be difficult to perform and can have poor results. We describe a
      method of hepaticojejunostomy done from within the Roux-en-Y loop, which can be
      utilized in this situation.

PMID- 9184865
TI  - Villous adenocarcinoma of the duodenum invading the ampulla of Vater case report
      and review of literature.
AB  - We report a case of villous adenocarcinoma of duodenum arising from the ampulla
      of Vater with a review of the literature. Although preoperative endoscopic
      biopsies were performed, no malignancy was identified. Because of the
      pathological uncertainty we decided to perform a pylorus-preserving
      pancreatoduodenectomy. Microscopic examination demonstrated glandular dysplasia
      with aspects of villous adenoma and well differentiated adenocarcinoma. We
      conclude that both in malignant cases and in cases with uncertain diagnosis a
      pylorus-preserving pancreatoduodenectomy is the best surgical treatment because
      it results in better 5 year survival.

PMID- 9184867
TI  - The management of extrahepatic portal vein aneurysms: observe or treat?
AB  - A case of a 70 year old man who was found to have an extrahepatic portal vein
      aneurysm during an evaluation for hematuria is reported. Extrahepatic portal vein
      aneurysms are rare with only twenty cases reported in the literature. Typically,
      patients present with hemorrhage requiring surgical exploration or the aneurysm
      is discovered during evaluation of another abdominal process. Management includes
      careful follow-up in the asymptomatic patient without underlying liver disease or
      portal hypertension.

PMID- 9184868
TI  - Obstructive jaundice associated with polycystic liver disease.
AB  - A 65 year old patient with polycystic liver disease presented with obstructive
      jaundice thought to be a cholangiocarcinoma. Subsequent investigations
      demonstrated a large cyst compressing the confluence of the hepatic ducts.
      Percutaneous decompression of the biliary tree led to a complication
      necessitating surgery. Treatment options for symptomatic polycystic liver disease
      are reviewed.

PMID- 9184869
TI  - Isolated resection of segment I (caudate lobe): is it justified?

PMID- 9184870
TI  - Liver resection: prolonged inflow occlusion in human cirrhotic livers.

PMID- 9184871
TI  - Improved results for resection of periampullary adenocarcinoma.

PMID- 9184872
TI  - Significance of liver size in hepatic surgery.
AB  - The purpose of this study was to evaluate the significance of liver volumetry as
      a parameter for hepatic functional reserve in cirrhotic patients with
      hepatocellular carcinoma. Liver volume was calculated from preoperative computed
      tomograms of 44 cirrhotic patients who underwent elective hepatic resections for
      hepatocellular carcinoma. The liver volume per body weight of non-alcoholic
      cirrhotics was significantly smaller than that of alcoholic cirrhotics (20.9 vs.
      26.7 cc/kg; p = 0.03). The values for alcoholic cirrhotics was comparable with
      normal values. The liver volume per body weight of the cirrhotic patients
      demonstrated correlation with the preoperative serum albumin (p < 0.01) and
      indocyanine green clearance (p = 0.02). We conclude that the determination of
      hepatic atrophy by volumetry can serve as a parameter for the assessment of
      hepatic reserve but not as a predictor of postoperative complications in elective
      liver surgery for cirrhotic patients.

PMID- 9184873
TI  - Nesidioblastosis in the adult surgical management.
AB  - Nesidioblastosis is an exceedingly rare occurrence in the adult and, when it
      appears, it is usually part of a MEA1 syndrome. We present a case of
      nesidioblastosis in a young woman, with no concurrent endocrine pathology, while
      we discuss in detail the diagnostic and therapeutic problems posed by this
      condition. The selected treatment was sub-total pancreatectomy (70-80%) and the
      histopathologic and immunohistochemical tests of the surgical specimen showed:
      "Diffuse Nesidioblastosis". The histopathologic and immuno-histochemical features
      of the resected pancreas are analysed in detail.

PMID- 9184874
TI  - Endoscopic retrograde cholangiopancreatography in the diagnosis and management of
      choledochal cysts.
AB  - Choledochal cysts are an uncommon anomaly of the biliary system manifested by
      cystic dilatation of the extra or intrahepatic biliary tree or both. It is most
      frequently found in Orientals and in females. Endoscopic retrograde
      cholangiopancreatography is a valuable imaging technique in the diagnosis of
      choledochal cysts in adults. Additionally, in selected cases, a choledochocele
      may be effectively managed by endoscopic sphincterotomy. We present clinical and
      endoscopic findings of six adult patients with choledochal cysts. Clinical
      symptoms were characterized by abdominal pain, jaundice and cholangitis.
      Associated hepatobiliary pathologic findings included cholelithiasis, recurrent
      acute pancreatitis, gallbladder carcinoma, Cystolithiasis, choledocholithiasis,
      biliary stricture and hepatic abscess.

PMID- 9184875
TI  - Iatrogenic biliary strictures: surgical experience with 39 patients.
AB  - The authors report their experience with surgical treatment of 39 patients with
      biliary strictures of iatrogenic origin. Patients were grouped according to the
      level of obstruction as described by Bismuth, and the type of repair was based on
      this classification. A total of 45 operations were performed, including those for
      recurrent strictures: 22 hepaticojejunostomies, 10 Hepp and Couinad's operations,
      6 choledochojejunostomies, 3 separate right and left hepaticojejunostomies, 1
      hepaticojejunostomy with mucosal graft (Smith's technique), 1 intrahepatic
      cholangiojejunostomy (Longmire's technique), 1 choledochoduodenostomy and 1
      choledochoplasty. Results were considered good if the patient was free of
      symptoms, jaundice or episodes of cholangitis, with serum alkaline phosphatase
      less than two-times the normal value. Minimum follow-up period of two years
      (obtained in 35 patients) was required to evaluate the results. Good results were
      obtained in 26 of those 30 patients (87%) who underwent only one biliary
      reconstruction, and in 3 of those 5 (60%) with more than one repair. Overall, 29
      patients (83% of those 35) presented good results. The complexity of the surgical
      treatment of biliary strictures imposes the adoption of measures to prevent
      lesions to the bile duct. Factors related to the prognosis that must be
      emphasized are surgeons' individual experience and skills, location of the
      stricture and diameter of the anastomosis.

PMID- 9184876
TI  - Multidisciplinary conservative treatment of difficult bile duct stones: a real
      alternative to surgery.
AB  - 56 patients with large CBD or intrahepatic stones underwent endoscopic and/or
      percutaneous treatment followed by extracorporeal shock wave lithotripsy.
      Percutaneous access to the biliary tract was chosen when an endoscopic approach
      was not possible (hepaticojejunostomy in 5 patients, 1 juxtapapillary
      diverticulum and 1 inflammatory bile duct stricture). Visualization of stones was
      achieved radiologically in 32 patients and by ultrasound in 24. The procedure was
      successful in 47 of 56 treated patients (83.9%). Clearance of the biliary tract
      was obtained in 25 cases (53%), whereas in 22 cases (47%) complete clearing of
      biliary tract was obtained only after endoscopic extraction of fragments (17
      cases) or percutaneous (5 cases). The median number of shock waves in each
      session was 1725 (range 300-3166), which were applied during one (n = 30), two (n
      = 22) or three sessions (n = 4). The only complications were 1 case of
      symptomatic hyperamylasemia and 3 cases of macrohematuria. In conclusion,
      extracorporeal lithotripsy combined with endoscopic and/or percutaneous treatment
      is a real alternative to surgery for difficult stones.

PMID- 9184877
TI  - Chronic pancreatitis and neoplasia: correlation or coincidence.
AB  - Any link between pancreatic carcinoma and chronic pancreatitis could reflect the
      malignant potential of a chronic inflammatory process. Four patients with ductal
      adenocarcinomas had a long history of pancreatic pain (median duration 5 years)
      and showed clear-cut evidence of chronic pancreatitis "downstream" of the tumour.
      Four were alcoholics and two heavy smokers. These four cases arose within a
      surgical series of approximately 250 patients with chronic pancreatitis, giving
      an incidence of 1.6 per cent. The incidence and anatomical distribution of
      carcinoma and chronic pancreatitis could possibly be consistent with a casual
      relationship.

PMID- 9184878
TI  - Collision tumour of the ampulla of Vater: carcinoid and adenocarcinoma.
AB  - Obstructive jaundice is most commonly due to luminal stones or lesions of the
      head of the pancreas and more rarely ampullary and primary common bile duct
      lesions. Obstruction due to lesions of the ampulla of Vater may be due to
      adenocarcinoma which has a significantly better long term prognosis than
      carcinomas located in the head of the pancreas. A case is presented where two
      tumours were identified at the ampulla of Vater of the resected specimen one an
      adenocarcinoma and the other a carcinoid tumour representing a collision tumour.

PMID- 9184879
TI  - Endoscopic management of perforation of right hepatic duct following non-surgical
      abdominal trauma.
AB  - Isolated bile duct injuries after blunt abdominal trauma are rare. Surgery is the
      usual mode of treatment. We report a patient with a right hepatic duct injury
      following blunt abdominal trauma who was managed successfully by endoscopic
      papillotomy.

PMID- 9184880
TI  - Delayed presentation of porta hepatis injury following blunt abdominal trauma.
AB  - A 73 year old lady developed abdominal pain, anaemia and obstructive jaundice 18
      days after a road traffic accident. The jaundice was due to compression of the
      biliary confluence by a haematoma which was caused by a laceration of the left
      portal vein. The portal vein was repaired (lateral venorrhaphy) and post
      operative recovery was uncomplicated. Porta hepatis injuries are difficult to
      diagnose and delayed presentation is not uncommon. Significant morbidity and
      mortality may ensue if aggressive management is not adopted.

PMID- 9184881
TI  - Emergency portacaval shunts: is Orloff correct?

PMID- 9184882
TI  - Prediction of the first variceal haemorrhage.

PMID- 9184883
TI  - Liver and pancreatic resection in the elderly.

PMID- 9184884
TI  - Pre-liver transplant: TIPS versus distal splenorenal shunt.

PMID- 9184885
TI  - Is hepatectomy necessary in dealing with left hepatolithiasis with intrahepatic
      duct stricture?

PMID- 9184886
TI  - Estimating the bias field of MR images.
AB  - We propose a modification of Wells et al. technique for bias field estimation and
      segmentation of magnetic resonance (MR) images. We show that replacing the class
      other, which includes all tissue not modeled explicitly by Gaussians with small
      variance, by a uniform probability density, and amending the expectation
      maximization (EM) algorithm appropriately, gives significantly better results. We
      next consider the estimation and filtering of high-frequency information in MR
      images, comprising noise, intertissue boundaries, and within tissue
      microstructures. We conclude that post-filtering is preferable to the
      prefiltering that has been proposed previously. We observe that the performance
      of any segmentation algorithm, in particular that of Wells et al. (and our
      refinements of it) is affected substantially by the number and selection of the
      tissue classes that are modeled explicitly, the corresponding defining parameters
      and, critically, the spatial distribution of tissues in the image. We present an
      initial exploration to choose automatically the number of classes and the
      associated parameters that give the best output. This requires us to define what
      is meant by "best output" and for this we propose the application of minimum
      entropy. The methods developed have been implemented and are illustrated
      throughout on simulated and real data (brain and breast MR).

PMID- 9184887
TI  - Mapping visual field with positron emission tomography by mathematical modeling
      of the retinotopic organization in the calcarine cortex.
AB  - We developed an objective and quantitative method of mapping the human visual
      field with positron emission tomography (PET) and magnetic resonance image (MRI).
      The regional cerebral blood flow (rCBF) images were acquired with H2(15)O-PET
      under visual fixation as well as under visual stimulation with flickering diodes
      arranged along the ring at 0 degree, 3 degrees, 7 degrees, 14 degrees, 21
      degrees, or 29 degrees from the fixation point. After coregistration of PET and
      MR images, we extracted the surface of the calcarine cortex from the MR images
      and unfolded it to a two-dimensional (2-D) elliptic plane, on which the activated
      PET images were superimposed. Then we transformed the unfolded calcarine cortex
      into the visual field coordinates using the complex logarithmic function proposed
      by Schwartz. A large individual variation was observed in the retinotopical
      organization as well as in the morphology of the calcarine cortex. The formula
      was valid only within 15 degrees from the center of the visual field. The
      constant parameter in the formula was estimated to be 1.5. The cortical linear
      magnification factor was 12.1, 2.8, and 1.6 at 0, 5, and 10 degrees,
      respectively. The areas of the central 10 degrees and 40 degrees in the visual
      field correspond to 50% and 81% of the calcarine surface, respectively.

PMID- 9184888
TI  - Characterization of dynamic 3-D PET imaging for functional brain mapping.
AB  - Methods for optimizing the acquisition, reconstruction and analysis of positron
      emission tomography (PET) images for functional brain mapping have been
      investigated. The scatter fraction and noise-equivalent count rate
      characteristics were measured for the ECAT 951/31R PET scanner operating in septa
      extended two-dimensional (2-D) and septa-retracted three-dimensional (3-D) modes.
      The 3-D mode is shown to provide higher signal-to-noise images than the 2-D mode
      at specific activities less than 30 kBq/ml. To enable increased temporal
      resolution in dynamic 3-D PET activation studies, a parallel version of the 3-D
      reconstruction algorithm was developed. Implementation of the reprojection
      algorithm on an 88 processor 1860 supercomputer resulted in a more than tenfold
      increase in reconstruction speed compared to a single 1860 processor system. An
      investigation of the optimal duration for imaging brain activations was
      undertaken in 12 normal subjects using repeated H2(15)O slow infusions and a
      visually presented lexical decision task. The significance of change in regional
      cerebral blood flow (CBF) was determined using statistical parametric maps for
      images acquired during stimulation, immediately after stimulation, and commencing
      1 min after cessation of the stimulus. Regions of CBF change were detected in all
      three images. Dynamic 3-D, or four-dimensional (4-D), PET activation scanning is
      shown to be practical and likely to further improve the sensitivity of PET for
      detection of subtle regional CBF changes in functional brain mapping research.

PMID- 9184889
TI  - Shape-based tracking of left ventricular wall motion.
AB  - An approach for tracking and quantifying the nonrigid, nonuniform motion of the
      left ventricular (LV) endocardial wall from two-dimensional (2-D) cardiac image
      sequences, on a point-by-point basis over the entire cardiac cycle, is presented.
      Given a set of boundaries, motion computation involves first matching local
      segments on one contour to segments on the next contour in the sequence using a
      shape-based strategy. Results from the match process are incorporated with a
      smoothness term into an optimization functional. The global minimum of this
      functional is found, resulting in a smooth flow field that is consistent with the
      match data. The computation is performed for all pairs of frames in the temporal
      sequence and equally sampled points on one contour are tracked throughout the
      sequence, resulting in a composite flow field over the entire sequence. Two
      perspectives on characterizing the optimization functional are presented which
      result in a tradeoff resolved by the confidence in the initial boundary
      segmentation. Experimental results for contours derived from diagnostic image
      sequences of three different imaging modalities are presented. A comparison of
      trajectory estimates with trajectories of gold-standard markers implanted in the
      LV wall are presented for validation. The results of this comparison confirm that
      although cardiac motion is a three-dimensional (3-D) problem, two-dimensional (2
      D) analysis provides a rich testing ground for algorithm development.

PMID- 9184890
TI  - Application of active contours for photochromic tracer flow extraction.
AB  - This paper addresses the implementation of image processing and computer vision
      techniques to automate tracer flow extraction in images obtained by the
      photochromic dye technique. This task is important in modeled arterial blood flow
      studies. Currently, it is performed via manual application of B-spline curve
      fitting. However, this is a tedious and error-prone procedure and its results are
      nonreproducible. In the proposed approach, active contours, snakes, are employed
      in a new curve-fitting method for tracer flow extraction in photochromic images.
      An algorithm implementing snakes is introduced to automate extraction. Utilizing
      correlation matching, the algorithm quickly locates and localizes all flow traces
      in the images. The feasibility of the method for tracer flow extraction is
      demonstrated. Moreover, results regarding the automation algorithm are presented
      showing its accuracy and effectiveness. The proposed approach for tracer flow
      extraction has potential for real-system application.

PMID- 9184891
TI  - Effects of time delay in cardiac blood flow measurements by bolus H2(15)O.
AB  - Myocardial blood flow (rMBF) can be measured using dynamic positron emission
      tomography (PET) and bolus injection of H2(15)O. Recent studies indicate that
      large errors in the estimates of flow (f) can be produced by time shifts between
      the true arterial input function and the measured input function [A(t)]. We have
      investigated this phenomenon further using A(t) derived from patient data, and
      using simulated myocardial time activity curves [M(t)]. We found that with
      judicious choice of scan parameters and region of interest (ROI) placement, these
      errors can be greatly reduced. In particular, when A(t) is measured from the left
      ventricular (LV) cavity, the bias in f is negligible over a wide range of
      circumstances. However, when A(t) is not measured from the LV cavity, the bias in
      flow can be large for short scans (< 2 min) or low flow values (f < 0.4
      ml/g/min). We show that the bias is primarily due to the spill-over term in the
      model that is most commonly used to compute rMBF and suggest some correction
      methods. We conclude that it is possible to avoid errors in estimates of flow due
      to time delay.

PMID- 9184892
TI  - A segmentation-based lossless image coding method for high-resolution medical
      image compression.
AB  - Lossless compression techniques are essential in archival and communication of
      medical images. In this paper, a new segmentation-based lossless image coding
      (SLIC) method is proposed, which is based on a simple but efficient region
      growing procedure. The embedded region growing procedure produces an adaptive
      scanning pattern for the image with the help of a very-few-bits-needed
      discontinuity index map. Along with this scanning pattern, an error image data
      part with a very small dynamic range is generated. Both the error image data and
      the discontinuity index map data parts are then encoded by the Joint Bi-level
      Image experts Group (JBIG) method. The SLIC method resulted in, on the average,
      lossless compression to about 1.6 h/pixel from 8 b, and to about 2.9 h/pixel from
      10 b with a database of ten high-resolution digitized chest and breast images. In
      comparison with direct coding by JBIG, Joint Photographic Experts Group (JPEG),
      hierarchical interpolation (HINT), and two-dimensional Burg Prediction plus
      Huffman error coding methods, the SLIC method performed better by 4% to 28% on
      the database used.

PMID- 9184893
TI  - A rapid and automatic image registration algorithm with subpixel accuracy.
AB  - A number of digital imaging techniques in medicine require the combination of
      multiple images. Using these techniques, it is essential that the images be
      adequately aligned and registered prior to addition, subtraction, or any other
      combination of the images. This paper describes an alignment routine developed to
      register an image of a fixed object containing a global offset error, rotation
      error, and magnification error relative to a second image. The described routine
      uses sparsely sampled regional correlation in a novel way to reduce computation
      time and avoid the use of markers and human interaction. The result is a fast,
      robust, and automatic alignment algorithm, with accuracy better than about 0.2
      pixel in a test with clinical computed radiography images.

PMID- 9184894
TI  - A physics-based coordinate transformation for 3-D image matching.
AB  - Many image matching schemes are based on mapping coordinate locations, such as
      the locations of landmarks, in one image to corresponding locations in a second
      image. A new approach to this mapping (coordinate transformation), called the
      elastic body spline (EBS), is described. The spline is based on a physical model
      of a homogeneous, isotropic three-dimensional (3-D) elastic body. The model can
      approximate the way that some physical objects deform. The EBS as well as the
      affine transformation, the thin plate spline [1], [2] and the volume spline [3]
      are used to match 3-D magnetic resonance images (MRI's) of the breast that are
      used in the diagnosis and evaluation of breast cancer. These coordinate
      transformations are evaluated with different types of deformations and different
      numbers of corresponding (paired) coordinate locations. In all but one of the
      cases considered, using the EBS yields more similar images than the other
      methods.

PMID- 9184895
TI  - Generating ROC curves for artificial neural networks.
AB  - Receiver operating characteristic (ROC) analysis is an established method of
      measuring diagnostic performance in medical imaging studies. Traditionally,
      artificial neural networks (ANN's) have been applied as a classifier to find one
      "best" detection rate. Recently researchers have begun to report ROC curve
      results for ANN classifiers. The current standard method of generating ROC curves
      for an ANN is to vary the output node threshold for classification. In this work,
      we propose a different technique for generating ROC curves for a two-class ANN
      classifier. We show that this new technique generates better ROC curves in the
      sense of having greater area under the ROC curve (AUC), and in the sense of being
      composed of a better distribution of operating points.

PMID- 9184896
TI  - MEG-based imaging of focal neuronal current sources.
AB  - We describe a new approach to imaging neural current sources from measurements of
      the magnetoencephalogram (MEG) associated with sensory, motor, or cognitive brain
      activation. Many previous approaches to this problem have concentrated on the use
      of weighted minimum norm (WMN) inverse methods. While these methods ensure a
      unique solution, they do not introduce information specific to the MEG inverse
      problem, often producing overly smoothed solutions and exhibiting severe
      sensitivity to noise. We describe a Bayesian formulation of the inverse problem
      in which a Gibbs prior is constructed to reflect the sparse focal nature of
      neural current sources associated with evoked response data. We demonstrate the
      method with simulated and experimental phantom data, comparing its performance
      with several WMN methods.

PMID- 9184897
TI  - Sampling concerns in scanline algorithms.
AB  - This paper investigates the problem of providing suitable interpolation for
      scanline algorithms. These algorithms are of interest, as they are
      parallelizable. A structure for analyzing the problem is given. The theory in
      regard to resampling is developed in the context of a scanline algorithm for
      image rotation. The theory is compared to results arrived at in practice.
      Alternative interpolation schemes are discussed, including the use of a cubic
      Hermite interpolator. The paper points to theoretical limitations of scanline
      algorithms.

PMID- 9184898
TI  - A system for converting print into braille.
AB  - This paper describes a method for converting text into braille, in the form in
      which it is stored as in a computer. The system has been designed to be
      configurable for a wide range of languages and character sets, and uses a
      predominantly table driven method to achieve this. The algorithm is explained in
      the context of the conversion of text into Standard English Braille (British),
      and the tables for this transformation are given. Particular importance has been
      attached to enabling braille specialists, who are not experts in computer
      algorithms, to be able to modify the system for either slight modifications to an
      existing braille code translator, or for producing a braille code translator for
      a new language.

PMID- 9184899
TI  - Uncertainty analysis for wheelchair propulsion dynamics.
AB  - Wheelchair propulsion kinetic measurements require the use of custom pushrim
      force/moment measuring instruments which are not currently commercially
      available. With the ability to measure pushrim forces and moments has come the
      development of several dynamic metrics derived for analyzing key aspects of
      wheelchair propulsion. This paper presents several of the equations used to
      calculate or derive the primary variables used in the study of wheelchair
      propulsion biomechanics. The uncertainties for these variables were derived, and
      then numerically calculated for a current version of the SMARTWheel. The
      uncertainty results indicate that the SMARTWheel provides data which has better
      than 5 to 10% uncertainty, depending upon the variable concerned, at the maximum,
      and during most of the propulsion phase the uncertainty is considerably smaller
      (i.e., approximately 1%). The uncertainty analysis provides a more complete
      picture of the attainable accuracy of the SMARTWheel and of the degree of
      confidence with which the data can be recorded. The derivations and results
      indicate where improvements in measurement of wheelchair propulsion biomechanical
      variables are likely to originate. The most efficient approach is to address
      those variables in the design of the system which make the greatest contribution
      to the uncertainty. Future research will focus on the point of force application
      and examination of nonlinear effects.

PMID- 9184900
TI  - A low-cost instrumented glove for monitoring forces during object manipulation.
AB  - A rehabilitation program toward restoring upper limb movements based on
      neuromuscular electrical stimulation (NMES) depends on closed-loop control
      performance, which has been limited by the development of sensors for practical
      daily use. This work proposes a system to obtain force feedback. The system is
      comprised of a Lycra commercial glove with force sensing resistors (FSR's)
      attached to the distal phalanxes of the thumb, index and long fingers. After
      amplification and filtering, the signal is digitized through an analog-to-digital
      (A/D) converter. The polynomial fitting coefficients for the characteristic
      curves, obtained during the sensor calibration process, were inserted in the
      software thus enabling the reading of forces exerted during object manipulation.
      The system was applied to 30 normal subjects in order to verify its feasibility
      and to acquire knowledge of the normal hand function. Different ways of grasping
      have been detected according to the Force versus Time curve pattern and to the
      fingers predominantly used in grasping. Results have also shown the influence of
      parameters such as gender, age, hand size, and object weight in the normal
      function. The system did show efficacy. It was able to determine grasp forces
      during object manipulation for up to 73% of the studied sample. This is
      significant since a single glove was used in a wide range of subjects. For best
      results in medical applications, the glove should be tailored to the particular
      characteristics of an individual user.

PMID- 9184901
TI  - Application of hydrogen absorbing alloys to medical and rehabilitation equipment.
AB  - As power sources for rehabilitation equipment, electric, hydraulic, and pneumatic
      actuators have been used. However a more human-sized and higher powered actuator
      that can reduce the equipment size is desired. A new metal hydride (MH) actuator
      that uses the reversible reaction between the heat energy and mechanical energy
      of a hydrogen absorbing alloy has recently attracted much attention. The MH
      actuator is characterized by its small size, low weight, noiseless operation and
      a compliance similar to that of the human elbow joint. Therefore, the MH actuator
      has the characteristic of being light and easy to use and so is suitable for use
      in medical and rehabilitation applications. Some lifting devices using this
      actuator have already been developed and are being used for the care of the aged
      and disabled. The characteristics of the MH actuator are presented and then some
      applications are introduced in this paper. It is our opinion that in our aging
      society the MH actuator will play an important role in the development of medical
      and rehabilitation equipment.

PMID- 9184902
TI  - Applying fuzzy logic to control cycling movement induced by functional electrical
      stimulation.
AB  - This study examines the design of a rational stimulation pattern for electrical
      stimulation and a robust closed-loop control scheme to improve cycling system
      efficacy for subjects with paraplegia. The stimulation patterns were designed by
      analyzing gravitation potential needed for the cycling movement of the lower
      limbs against a frictionless cycling ergometer and the response delay of
      electrically stimulated muscles. To simplify the cycling control system, the
      stimulation patterns were fixed and only the single gain of the stimulation
      patterns was adjusted via a feedback control algorithm. To circumvent the
      complexity involved with exactly modeling a stimulated muscle and cycling
      ergometer, a model-free fuzzy logic controller (FLC) was adopted herein for our
      control scheme. Comparison between FLC and conventional proportional-derivative
      (PD) controllers demonstrated that the FLC with asymmetrical membership function
      enabled the subject with paraplegia to maintain varied desired cycling speeds,
      particularly at lower cycling speed. By incorporating the rational stimulation
      patterns, the FLC can produce a smooth and prolonged cycling movement deemed
      necessary for designing various training protocols.

PMID- 9184903
TI  - The validity of stimulus-evoked EMG for studying muscle fatigue characteristics
      of paraplegic subjects during dynamic cycling movement.
AB  - The fatigue characteristics of paralyzed muscles were investigated during dynamic
      cycling movement induced by functional electrical stimulation (FES). The peak-to
      peak (PTP) amplitude of stimulus-evoked electromyogram (EMG), after suppression
      of stimulus artifact, was adopted as fatigue indicator. Compared to static
      contraction, the effects of dynamic movement factors on the stimulus-evoked EMG,
      such as the intermittent stimulation, joint angle, and contraction speed, were
      first evaluated in separate experiments. The results of isolated tests laid the
      foundation for interpreting the data obtained in two FES-cycling experiments,
      performed under maximum stimulation or in controlled cycling speeds. The effects
      of intermittent stimulation and joint angle caused periodic changes in PTP
      amplitude which can be alleviated by averaging the PTP amplitude of one cycle.
      Under the same stimulation intensity, our results indicated that slower muscle
      contraction speed would have larger PTP amplitude and vice versa. For the limited
      number of subjects with paraplegia studied, our results showed that the use of
      EMG PTP as reliable muscle fatigue indicator during dynamic movement is only
      valid at the same cycling speed or corresponding contraction speed. The decline
      of the PTP amplitude decreased with the decay of muscle force can be observed
      during cycling movement; however, reduction of cycling speed had the opposite
      effect on PTP amplitude. Observations from the hyperbolic modeling of fatigue
      process demonstrated that the EMG PTP of a fatigued muscle under dynamic movement
      decreased at a slower rate.

PMID- 9184904
TI  - A nonlinear mathematical model of electrically stimulated skeletal muscle.
AB  - A new biophysically based mathematical model for a human musculotendon system is
      presented. This model is developed specifically for skeletal muscle activated by
      functional electrical stimulation (FES). The reverse-order recruitment dynamics
      of FES activated systems are modeled, as are the underlying processes of force
      generation in mammalian muscle. The resulting system model is both nonlinear and
      highly coupled, reflecting the fundamental structure and behavior of skeletal
      muscle. A new heterogeneous model structure for a contractile element is also
      presented that overcomes many of the problems which arise when attempting to
      describe all possible contraction modes. It is found that the new model is
      robust, numerically stable, and easily implemented. Simulation results are
      presented that demonstrate the model's ability to capture a variety of nonlinear
      behaviors observed in skeletal muscle activated by FES. Significant insight into
      the internal dynamics of force development in FES muscle may also be gained from
      the model. This model is intended as a possible alternative to those currently
      available in the literature. It may be of use to those conducting research into
      the modeling, control and optimization of FES generated motion, and neural
      feedback systems.

PMID- 9184905
TI  - Functional neuromuscular stimulation controlled by surface electromyographic
      signals produced by volitional activation of the same muscle: adaptive removal of
      the muscle response from the recorded EMG-signal.
AB  - In order to use the volitional electromyography (EMG) as a control signal for the
      stimulation of the same muscle, it is necessary to eliminate the stimulation
      artifacts and the muscle responses caused by the stimulation. The stimulation
      artifacts, caused by the electric field in skin and tissue generated by the
      stimulation current, are relatively easy to eliminate by shutting down the EMG
      amplifier at the onset of the stimulation pulses. The muscle response is a
      nonstationary signal, therefore, an adaptive linear prediction filter is
      proposed. The filter is implemented and for three filter lengths tested on both
      simulated and real data. The filter performance is compared with a conventional
      fixed comb filter. The simulations indicate that the adaptive filter is
      relatively insensitive to variations in amplitude of the muscle responses, and
      for all filter lengths produces a good filtering. For variations in shape of the
      muscle responses and for real data, an increased filter performance can be
      achieved by increasing the filter length. Using a filter length of up to seven
      stimulation periods, it is possible to reduce real muscle responses to a level
      comparable with the background noise. Using the shut-down circuit and the
      adaptive filter both the stimulation artifacts and the muscle responses can be
      effectively eliminated from the EMG signal from a stimulated muscle. It is
      therefore possible to extract the volitional EMG from a partly paralyzed muscle
      and use it for controlling the stimulation of the same muscle.

PMID- 9184906
TI  - Tissue response to chronically stimulated implanted epimysial and intramuscular
      electrodes.
AB  - Twenty-four epimysial and 16 intramuscular electrodes were implanted in five
      adult dogs for periods ranging from 11 to 50 months. Chronic stimulation was
      applied to half of the electrodes for eight weeks near the end of the
      implantation period. The tissue response was rated by the amount and appearance
      of the fibrous tissue and inflammatory cells seen in the capsule lining the
      region of the electrode. The encapsulation tissues were composed primarily of
      collagen and fibroblasts and some macrophages and few other inflammatory cells.
      The epimysial electrodes exhibited more variation between and within electrodes,
      but had more of the better scores than the intramuscular electrodes. No
      difference in the distribution of scores was measured between the control and
      stimulated groups for the epimysial electrodes. While the scores for the intra
      muscular electrodes varied very little, variance was sufficient to indicate a
      trend for poorer ratings with the application of chronic stimulation. Fibrous
      capsules were generally thinner under the epimysial electrodes than around the
      intramuscular electrodes. For both electrode types, the thickness was not
      correlated with the application or level of chronic stimulation. Thickness was
      shown to be positively correlated to the degree of loss of the sutures used to
      anchor the epimysial electrodes.

PMID- 9184907
TI  - Enhanced rehabilitation of gait after stroke: a case report of a therapeutic
      approach using multichannel functional electrical stimulation.
AB  - The beneficial effects of using multichannel functional electrical stimulation
      (MFES) for gait rehabilitation in nonambulatory hemiplegic patients have already
      been shown. The methodology of application and the results presented were pooled
      for the whole group of participants, which blurs the exact picture of each
      particular subject and many vital details are not presented. The purpose of this
      article is to focus on a single subject from the study and to present all the
      details of the treatment. The presented subject participated six weeks in the
      study, first three weeks in MFES therapy and second three weeks in conventional
      therapy. The effects of each therapy were evaluated by the following measures:
      temporal-distance parameters of gait, ground reaction forces, goniograms in hip
      knee and ankle, and assessment of the physical status of the patient according to
      the Fugl-Meyer evaluation scale. An analysis of the measured parameters showed
      improved performance of the patient during MFES therapy and stagnation or even
      slight recession during conventional therapy. The patient achieved independent
      gait during the three weeks of MFES therapy. At 30 months after the beginning of
      therapy, the patient was still able to ambulate independently without any
      significant changes in his gait pattern. The accomplishment was mainly attributed
      to the avoidance of pathological gait pattern development by using MFES assisted
      gait training and to the high motivation of the patient to walk and exercise
      during therapy as well as after he was released to go home.

PMID- 9184908
TI  - The monitoring of tendon tension with an implantable intratendon probe and its
      use in the control of neuroprostheses.
AB  - The use of a probe measuring tendon tension for the purpose of controlling a
      neuroprosthesis suited to spinal cord injured persons is investigated. The
      implanted probe detected inwardly directed radial force exerted by the tendon as
      the result of longitudinal tension. Varying types of load were applied to the
      tendon in order to measure static and dynamic parameters of the probe within the
      tendon. The results are discussed with respect to the potential use of the probe,
      within an active muscle's tendon, as a hand grasp neuroprosthesis controller. In
      addition, use of the probe to monitor electrically stimulated paralyzed muscle
      for the augmentation of closed loop control schemes is discussed.

PMID- 9184909
TI  - Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed
      T helper type 2 and B cells.
AB  - The interaction between CD28 and its ligands, CD80 and CD86, is crucial for an
      optimal activation of antigen-specific T cells. However, the requirement of CD80
      or CD86 co-stimulation in Th2 cell differentiation and activation is
      controversial. Freshly isolated murine CD4+ and CD8+ T cells were incubated with
      P815 transfectants expressing a similar level of either CD80 or CD86 in the
      presence of anti-CD3 mAb. Both CD80 and CD86 co-stimulated the proliferation of
      CD4+ and CD8+ T cells at comparable time-kinetics and magnitude, but CD86 alone
      was able to co-stimulate IL-4 and especially IL-10 production in CD4+ T cells. In
      typical Th2-dependent immune responses elicited by Nippostrongylus brasillensis
      infection, the anti-CD86 mAb treatment but not the anti-CD80 mAb treatment
      efficiently inhibited antigen-specific IgE and IgG1 production, which was
      accompanied with the reduced IL-4 production. Our results suggest that CD86 co
      stimulation plays a dominant role not only in the primary activation of Th2 cells
      but also in the secondary interaction between antigen-primed Th2 cells and B
      cells.

PMID- 9184910
TI  - HLA-G functions as a restriction element and a transplantation antigen in mice.
AB  - HLA-G, a human MHC class I molecule expressed on the trophoblast during
      pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a
      transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA
      G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves
      as a xenotransplantation antigen in mice. Further investigation revealed that
      murine T cells recognize native HLA-G directly as a xenoantigen or they recognize
      processed peptides derived from HLA-G presented in the context of murine MHC
      molecules. HLA-G molecules also function as restriction elements capable of
      presenting peptides to murine T cells since immunization of HLA-G transgenic mice
      with peptide that binds specifically to HLA-G molecules elicited HLA-G
      restricted, cytotoxic T cell responses. In addition, murine T cell responses to
      human xenoantigens are enhanced when responder cells originated from HLA-G
      transgenic mice. Based on these observations, we conclude that expression of HLA
      G molecules influences selection of the murine T cell repertoire and that HLA-G
      exhibits immunological properties that are indistinguishable from classical HLA
      class I molecules when expressed in transgenic mice. Thus, any unique
      immunological functions mediated by HLA-G must arise from the distinctive,
      trophoblast-specific pattern of HLA-G expression in humans and not from
      structural peculiarities of HLA-G molecules.

PMID- 9184911
TI  - Restricted CDR3 length of the heavy chain is characteristic of six randomly
      isolated disease-associated VH J558+ IgM autoantibodies in lupus prone motheaten
      mice.
AB  - To investigate the origin of disease-associated IgM autoantibodies (AAb), we
      compared the genetic and structural characteristics of IgM AAb from autoimmune
      prone motheaten (mev) mice with natural autoantibodies (NAAb) from normal
      background C57/BL6 strain. Six hybridoma-derived IgM molecules each were obtained
      both from mev mice, at the terminal stage of systemic autoimmune disease, and
      from mitogen-stimulated C57/BL6 mice. These were randomly selected for VH J558
      gene expression (aberrantly expressed in mev mice). The variable regions of the
      IgM molecules, both from autoimmune and normal mice, were encoded by unmutated
      germline VH genes. Disease-associated AAb from mev mice were predominantly
      encoded by the J558 subfamily 186.2, whereas five J558 subfamilies were utilized
      in NAAb originating from normal mice. Junctional diversity as a result of N or P
      nucleotide insertions and D-D fusions was noted among IgMs originating from both
      mev (mostly B-1 lymphocytes) and C57BL/6 (mostly B-2 lymphocytes) mice.
      Interestingly, all six J558+ IgMs from mev mice showed a restricted CDR3 length
      of 10 amino acids, with similar hydrophobicity indices. Four unique V-D-J
      rearrangements were observed among these IgMs. None of the IgMs were polyreactive
      and three of the six were subsequently observed to express monospecific
      autoreactivity with synthetic peptides (residues 81-92 and 37-53) representing
      segments of the T cell CD4-accessory molecule. Three IgM antibodies had
      hydrophilic arginine residues in their CDR3 heavy chain region. By contrast, all
      six J558+ IgMs from C57/BL6 mice had variable CDR3 length, distinct VDJ
      rearrangements and a local negative charge in the CDR3 region. Four of these IgMs
      demonstrated polyreactivity with multiple conserved autoantigens and, hence, were
      classified as NAAb. These findings provide evidence for either positive or
      impaired negative selection of B-1 lymphocytes secreting disease-associated IgM
      AAb in mev mice. This likely results from a reduced threshold of responsiveness
      to autoantigens due to PTP1C deficiency, which is targeted at the CDR3 length of
      the variable region of the heavy chain. In addition, characteristic differences
      in the size and hydrophobicity pattern of the CDR3 of the heavy chain allow
      structural distinction between monospecific disease-associated IgM AAb and the
      polyreactive IgM NAAb.

PMID- 9184912
TI  - Sequence changes at the V-D junction of the VH1 heavy chain of anti
      phosphocholine antibodies alter binding to and protection against Streptococcus
      pneumoniae.
AB  - X-linked immune deficient (Xid) mice fail to produce anti-phosphocholine (PC)
      antibodies even after immunization with Streptococcus pneumoniae. Consequently,
      Xid mice are extremely susceptible to infection with S. pneumoniae, PC-specific B
      cells appear to undergo clonal deletion in Xid mice; however, a new thymus
      dependent form of PC, 6-(O-phosphocholine)hydroxyhexanoate (EPC), can rescue PC
      specific B cells from the bone marrow presumably by providing T cell help before
      clonal deletion. Analysis of PC-specific IgG hybridomas from Xid mice revealed
      utilization of several V-D junctional variants of the VH1 gene segment rearranged
      to different D and JH gene segments. The majority of Xid anti-PC antibodies
      exhibit an Asp-->Gly95H replacement at the V-D junction. These Gly95H VH1
      variants associate with kappa 1C L chains to produce anti-PC antibodies that: (1)
      have low relative affinity for PC, (ii) are heteroclitic for
      nitrophenylphosphocholine and (iii) fall to bind to or provide protection against
      S. pneumoniae. Single prototypic V-D variants of the T15 idiotype (Asp95H), M603
      idiotype (Asn95H) and M167 idiotype (Asp95H-Ala96H) were also induced in Xid
      mice. The M603-like and M167-like antibodies bound to and protected against S.
      pneumoniae even though they exhibited Kas for PC which were lower than T15
      idiotype+ antibodies. These data demonstrate that small changes in the V-D
      junctional sequence of the T15 (VH1) heavy chain alter L chain usage and the
      structure of the PC binding site so that the PC expressed on S. pneumoniae is no
      longer recognized.

PMID- 9184913
TI  - Intravenous administration of deaggregated mouse thyroglobulin suppresses
      induction of experimental autoimmune thyroiditis and expression of both Th1 and
      Th2 cytokines.
AB  - Experimental autoimmune thyroiditis (EAT) can be induced by transfer of mouse
      thyroglobulin (MTg) and lipopolysaccharide (LPS)-immunized, MTg-activated spleen
      cells into syngeneic recipients. Recipients of MTg-activated T cells develop
      lymphocytic EAT, whereas recipients of cells activated by MTg and anti-IL-2R
      antibody develop a more severe and histologically distinct granulomatous form of
      EAT. Intravenous administration of deaggregated MTg (dMTg) 7 days before and 5
      days after the first immunization of donor mice with MTg/LPS suppresses the
      induction of both forms of EAT. Thyroid infiltration is significantly decreased
      in recipients of effector cells from tolerant donors. MTg-specific T cell
      proliferation is partially suppressed in tolerant mice. Both IgG1 and IgG2a
      subclasses of anti-MTg autoantibodies are markedly inhibited in both tolerant
      donor mice and in recipients of tolerant spleen cells. Expression of T cell
      cytokine gene transcripts (IL-2, IFN gamma, IL-4, IL-10, tumor necrosis factor
      alpha and transforming growth factor-beta) are all decreased in spleen cells of
      donor mice given dMTg. CD8+ T cells were not required for expression of tolerance
      since depletion of CD8+ T cells in vivo before tolerance induction or in vitro
      before MTg re-stimulation did not abrogate tolerance induction. Taken together,
      these results suggest that i.v. administration of dMTg can induce MTg-specific
      tolerance in both Th1- and Th2-like EAT effector cell precursors, and therefore
      prevent induction of adoptively transferred EAT.

PMID- 9184915
TI  - Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV
      infections.
AB  - Decline in blood CD4+ lymphocytes during primary symptomatic infections with HIV
      is usually attributed to viral killing, and has not been considered in terms of
      altered lymphocyte migration and sequestration. We therefore sought to examine
      whether CD4+ cell loss from blood of macaques undergoing an acute primary SIV
      infection might be due to increased synthesis of cytokines, known to profoundly
      affect lymphocyte trafficking, rather than to direct lymphocyte destruction by
      virus. The findings indicate that rapid lymphocyte depletion following acute
      infection is not selective for CD4+ cells, correlates precisely with increased
      plasma IFN-gamma and tumor necrosis factor-alpha levels, and is reversible.
      CD4/CD8 ratios in lymph nodes with high viral burdens remain relatively unchanged
      despite lymphocyte loss from blood. Levels of cytokine mRNA measured in lymphoid
      organs reflect neither cytokine plasma levels nor their potential to induce
      sequestration. These results support a model of cytokine-induced lymphocyte
      extravasation to account for the acute HIV/SIV-induced CD4+ cell lymphopenia and
      raise questions regarding the extent to which altered lymphocyte migration plays
      a role in the gradual CD4+ cell depletion throughout infection.

PMID- 9184914
TI  - Frequent occurrence of identical heavy and light chain Ig rearrangements.
AB  - Single-cell PCR analyses of expressed Ig H and L chain sequences presented here
      show that certain rearrangements occur repeatedly and account for a major segment
      of the well-studied repertoire of B-1 cell autoantibodies that mediate the lysis
      of bromelain-treated mouse erythrocytes, i.e. antibodies reactive with
      phosphatldyicholine (PtC). We repeatedly isolated at least 10 different types of
      VH region rearrangements, involving three distinct germline genes, among FACS
      sorted PtC-binding B-1 cells from three strains of mice (C57BL/6J, BALB/c and C.B
      17). The predominant rearrangement, VH11-DSP-JH1 (VH11 type 1), has been
      previously found in anti-PtC hybridomas in several studies. We show that within
      each of six mice from two strains (C57BL/6J and BALB/c), unique instances of
      IgH/IgL pairing arose either from different B cell progenitors prior to IgH
      rearrangement or from pre-B cells which expanded after IgH rearrangement but
      prior to IgL rearrangement. Together with other recurrent rearrangements
      described here, our findings demonstrate that clonal expansion of mature B cells
      cannot account for all repeated rearrangements. As suggested by initial studies
      of dominant idiotype expression, these findings confirm that clonal expansion is
      only one of the mechanisms contributing to the establishment of recurrent
      rearrangements.

PMID- 9184916
TI  - Human CD30+ cells are induced by Mycobacterium tuberculosis and present in
      tuberculosis lesions.
AB  - CD30 is a member of the tumor necrosis factor/nerve growth factor receptor family
      and evidence has been presented that activated CD4+ CD45Ro+ T cells of Th2 type
      selectively express CD30. Mycobacterium tuberculosis, a facultative intracellular
      bacterium capable of replicating in resting macrophages, is a potent inducer of
      IFN-gamma secretion by Th1 cells. We find increased CD30 expression by M.
      tuberculosis-stimulated alpha beta and gamma delta T cells, and elevated numbers
      of CD30+ alpha beta T cells in tuberculosis pleuritis and affected lung tissue.
      Furthermore, surface CD30 was associated with intracytoplasmic IFN-gamma
      expression and IFN-gamma production by M. tuberculosis-stimulated alpha beta and
      gamma delta T cells. Thus, our results indicate that M. tuberculosis is a potent
      inducer of CD30 expression in Th1 cells and argue against exclusive correlation
      of CD30 expression with Th2 cell responses.

PMID- 9184917
TI  - Production of both IFN-gamma and IL-5 by Onchocerca volvulus S1 antigen-specific
      CD4+ T cells from putatively immune individuals.
AB  - Protective immunity to the parasitic nematode Onchocerca volvulus (Ov) appears to
      be directed against molecules of invading L3 larvae. In this study, the cellular
      immune reaction to such an Ov L3 protein (S1) which is protective in an animal
      model was analyzed using peripheral blood mononuclear cells (PBMC) of individuals
      from a hyperendemic area in West Africa who were exposed to Ov but remained free
      from disease ('putatively immune individuals'). Despite seronegativity of these
      individuals against S1, proliferation of PBMC was inducible, allowing generation
      of an S1-specific T cell line which produced IFN-gamma upon stimulation with both
      Ov lysate and S1. However, S1 induced significantly more IL-5 than Ov lysate. S1
      specific, DQ6 (DQA1*0103/DQB1*0603)-restricted T cell clones were generated which
      reacted against synthetic peptides comprising amino acids 99-111 of S1. These
      clones, which are the first generated against a recombinant fllarial antigen,
      produced both IFN-gamma and IL-5 as well as little IL-4, suggestive of a Th0-like
      phenotype. In conclusion, in putative immunity, reactivity against a particular
      parasite protein can be detectable on the level of T but not B cells. Induction
      of both IFN-gamma and IL-5 by S1 suggests that it may trigger macrophage plus
      eosinophil dependent killing of L3 in vivo. The identification of a likely DQ6
      (DQA1*0103/DQB1*0603)-restricted T cell epitope may be of more general relevance,
      given that allele combinations of DQ6, including DQA1*0103/DQB1*0603, are
      negatively associated with diabetes mellitus.

PMID- 9184918
TI  - Recombinant vaccinia viruses for the characterization of Plasmodium falciparum
      specific cytotoxic T lymphocytes: recognition of processed antigen despite
      limited re-stimulation efficacy.
AB  - Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium
      falciparum infection and disease. We have previously described the use of
      peptides to define malaria-specific CTL epitopes. To determine whether these
      peptide epitopes are processed intracellularly from the whole antigen we have
      developed recombinant vaccinia viruses (rVV) expressing three malaria antigens:
      thrombospondin-related adhesive protein (TRAP), Pfs16 and the C-terminal half of
      liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were
      lysed by malaria-specific CTL from semi-immune African donors. We also tested the
      ability of cells infected with these recombinant vaccinia viruses to re-stimulate
      malaria-specific CTL in peripheral blood lymphocytes from malaria immune adults.
      Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC,
      a canarypox virus, both expressing malaria antigens were also evaluated for their
      ability to stimulate malaria-specific CTL in contrast to peptide, none of these
      viruses successfully re-stimulated CTL from the peripheral blood lymphocytes of
      semi-immune donors. The ability of human CTL from naturally exposed individuals
      to recognize processed antigen supports the relevance of these cells in
      protective immunity to malaria.

PMID- 9184919
TI  - Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1
      in synovial lining cells from rheumatoid arthritis patients.
AB  - Several investigators have demonstrated an association between Epstein-Barr virus
      (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no
      direct evidence that this virus exists in the synovial cells of patients with RA.
      We attempted to detect EBV in synovial cells from RA patients. Specimens of
      synovial tissues from 34 patients with RA and from 20 patients with
      osteoarthritis (OA), and from one patient with psoriatic arthritis as controls,
      were examined for evidence of the EBV by in situ hybridization. The specimens
      were also tested by immunoperoxidase staining for expression of the CD21 molecule
      (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1.
      EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from
      eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor
      in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial
      lining cells that were located at the apex of villus proliferating lesions.
      Furthermore, LMP-1 was also detected in synovial lining cells at the top of
      villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not
      demonstrated in such lesions. The incidence of EBV-positive in synovial lining
      cells with severely infiltrated lymphocytes tended to be higher than that in
      moderately infiltrated ones. This is the first evidence that EBV exists in
      chronically inflamed synovial lining cells of human joints in RA.

PMID- 9184920
TI  - IL-12 directly stimulates expression of IL-10 by CD5+ B cells and IL-6 by both
      CD5+ and CD5- B cells: possible involvement in age-associated cytokine
      dysregulation.
AB  - Constitutive expression of p35 and p40 IL-12 mRNA was detected in splenic
      macrophages isolated from aged mice. Macrophages were also implicated as the cell
      type responsible for the dysregulated IL-6 and tumor necrosis factor (TNF)-alpha
      commonly observed to be constitutively produced by lymphoid cells from aged
      donors. A role for IL-12 in the aging process was suggested when it was found
      that recombinant IL-12 (rIL-12) directly stimulated splenic CD5+ B cells to
      secrete IL-10, and both CD5+ and CD5- B cells could be directly induced to
      produce IL-6 in response to rIL-12. Furthermore, splenocytes from aged animals
      cultured in the presence of anti-IL-12 antibodies demonstrated a significant
      reduction in spontaneous IL-6, IL-10 and IFN-gamma production. Based on these
      observations it was concluded that IL-12 might be responsible for the
      dysregulated production of IL-10 and IFN-gamma known to occur in aged animals.
      Treatment of aged animals with low doses of dehydroepiandrosterone sulfate,
      previously established to be immunocorrective in immunosenescent animals, reduced
      the age-associated alterations in IL-12 mRNA and protein expression. The
      mechanisms responsible for the abnormal constitutive expression of inflammatory
      cytokines by the macrophages of aged animals may play an important afferent role
      in establishing the immunosenescent phenotype.

PMID- 9184922
TI  - External calcium-dependent, F-actin-independent and pertussis toxin-insensitive
      novel neutrophil locomotion induced by a mAb.
AB  - We previously demonstrated that a mAb to human neutrophils, designated 3H9, which
      was established by screening for inhibition of neutrophil adherence to plastic
      plates containing fetal bovine serum, enhanced both n-formyl-methionyl-leucyl
      phenylalanine (FMLP)-induced chemotaxis and random migration of neutrophils. In
      the present study, we examined the mechanisms of 3H9-induced enhancement of
      neutrophil locomotion in the phagokinetic track assay. 3H9-induced neutrophil
      locomotion maintained a straight path which was different from the track
      resulting from FMLP-stimulated locomotion. This 3H9-induced migration required
      extracellular Ca2+. beta 2-Integrin activation was a prerequisite for the
      increase in cytosolic free calcium induced by 3H9 treatment. However, stimulation
      by 3H9 did not induce an increase in F-actin, even after CD18 activation. Signal
      transduction after molecular recognition by 3H9 was not mediated by pertussis
      toxin-sensitive, heterotrimeric G proteins. These results suggest that 3H9
      enhances neutrophil migration by mechanisms which are different from those
      involved in usual chemoattractant-induced migration. Neutrophil surface molecules
      recognized by 3H9 may play a crucial role in the regulation of transendothelial
      migration of leukocytes.

PMID- 9184921
TI  - Differential sensitivity of B lymphocyte populations to IgM receptor ligation is
      determined by local factors.
AB  - Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS)
      suppresses terminal differentiation and high-rate Ig secretion with no effect on
      proliferation. As shown here, different B cell populations show characteristic
      mean values of ligand concentration required for 50% inhibition, with Gaussian
      distributions of sensitivity to IgM receptor ligation that reflect cellular
      heterogeneity of 'al-or-none' inhibitions in single cells. Differential
      sensitivity of B cell populations to IgM ligation seems to be locally determined
      by the cellular environment and unrelated to the 'maturity' of the responding
      cells. Thus, while long-lived peritoneal B cells are 3- to 5-fold more resistant
      than splenic B cells, there is no difference in sensitivity between short- and
      long-lived B cells in the spleen. Furthermore, while B cells in bone marrow and
      spleen differ in sensitivity by two orders of magnitude, B cells differentiated
      in vitro from bone marrow pre-B cells are as resistant as splenic B cells.
      Moreover, bone marrow cell culture supernatants restore a high level of
      sensitivity in such cell populations. Differential sensitivity to IgM receptor
      ligation is reproduced by multivalent nominal antigen, in cell populations that
      show identical dose-response inhibition curves to direct activation of protein
      kinase C by phorbol esters. We conclude that the level of sensitivity to IgM
      ligation is independent of the life span or maturity of the B cell, but
      differentially regulated in vivo by putative tissue factors.

PMID- 9184923
TI  - Is structural flexibility of antigen-binding loops involved in the affinity
      maturation of anti-DNA antibodies?
AB  - Effects of somatic mutations in Ig variable region genes on the affinity
      maturation of autoantibodies were investigated using single precursor B cell
      derived anti-double-stranded DNA mAb generated from an autoimmune disease-prone
      (NZB x NZW)F1 mouse. Analyses of DNA sequences, homology modeling on a graphic
      computer and molecular dynamics simulation of antigen-binding sites showed that
      any single site of mutation and changes in the electrostatic or hydrogen-bonding
      potential of the residues and in the three-dimensional structure could not solely
      explain the difference in DNA-binding activities. However, a significant increase
      in the flexibility of antigen-binding Fv loops, particularly VL CDR1 and VH CDR3,
      was associated with affinity-maturated anti-DNA antibodies. Such high flexibility
      of the FV loops may provide the environment where the antibodies could
      effectively interact with antigen DNA, a model consistent with the 'induced-fit'
      hypothesis of antigen-antibody interactions.

PMID- 9184924
TI  - Competitive control of the self-renewing T cell repertoire.
AB  - We develop a mathematical model for the self-renewing part of the T cell
      repertoire. Assuming that self-renewing T cells have to be stimulated by
      immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting
      cells, we derive a model of T cell growth in which competition for MHC-peptide
      complexes limits T cell clone sizes and regulates the total number of self
      renewing T cells in the animal. We show that for a sufficient diversity and/or
      degree of cross-reactivity, the total T cell number hardly depends upon the
      diversity of the T cell repertoire or the diversity of the set of presented
      peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity,
      steady-state total T cell numbers may be limited by the diversity of the T cells.
      This provides a possible explanation for the limited repertoire expansion in
      some, but not all, mouse T cell re-constitution experiments. We suggest that the
      competitive interactions described by our model underlie the normal T cells
      numbers observed in transgenic mice, germ-free mice and various knockout mice.

PMID- 9184926
TI  - Experimental autoimmune encephalomyelitis in IL-4-deficient mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) in an inflammatory demyelinating
      disease which usually follows a monophasic course. Autoreactive Th1 CD4+ T cells
      are responsible for the lesions, whereas autoreactive Th2 CD4+ T cells can, upon
      adoptive transfer, suppress the disease process. However, the role of IL-4 and
      Th2 cells in the spontaneous remission of EAE and in the prevention of relapses
      is not known. We have addressed these issues using IL-4-deficient mice in which
      the differentiation of Th2 CD4+ T cells is severely compromised. The clinical
      course of actively induced EAE was compared in IL-4+/+, IL-4+ /- and IL-4-/- mice
      on the PL/J genetic background. No significant differences were noted between
      groups for the frequency, severity and duration of EAE, and the frequency of
      relapses. Our results indicate that IL-4, despite its well-documented regulatory
      role in EAE, is not necessary for the spontaneous remission of disease or for the
      prevention of relapses. Therefore, in the absence of IL-4, overlapping or
      compensatory immunoregulatory mechanisms can restrict an inflammatory response
      within the central nervous system.

PMID- 9184925
TI  - Cytotoxic T lymphocytes derived from bone marrow mononuclear cells of multiple
      myeloma patients recognize an underglycosylated form of MUC1 mucin.
AB  - MUC1 is a highly immunogenic epithelial mucin and serves as a tumor-associated
      antigen in breast, pancreatic and ovarian carcinomas. We previously reported the
      expression of MUC1 on myeloma cells and the establishment of an HLA-unrestricted
      cytotoxic T lymphocyte (CTL) line TN that recognized MUC1 from peripheral blood
      mononuclear cells in a multiple myeloma patient. In this study, we attempted to
      induce such CTL from six other multiple myeloma patients consecutively in order
      to show that the induction of the CTL line TN had not resulted from some
      idiosyncrasy of the first patient. Bone marrow mononuclear cells were used to
      induce CTL, because they contain myeloma cells that might stimulate the
      autologous lymphocytes. Bulk CTL lines were induced from two out of six patients.
      The CTL line TS was CD8+ cell dominant and KY was CD4+ cell dominant. Both CTL
      lines lysed MUC1+ myeloma and breast carcinoma cell lines. The cytotoxicity of
      the CTL lines was inhibited by anti-CD3, anti-alpha beta TCR and anti-MUC1 mAb.
      It was also inhibited by a MUC1 transfectant, but not by a mock transfectant in
      cold target inhibition assays. MUC1 was transfected into a human colonic
      carcinoma cell line. The reactivity of anti-MUC1 core protein mAb and the
      cytotoxicity of the CTL against the transfectant was enhanced by the treatment of
      the cells with an O-glycosylation inhibitor. Thus it is generally accepted that
      the HLA-unrestricted CTL which directly recognize the underglycosylated from of
      MUC1 using their TCR could be induced from a certain proportion (approximately
      30%) of untreated multiple myeloma patients.

PMID- 9184927
TI  - Rational design of nematode vaccines: hidden antigens.
AB  - Hidden antigens are defined and the general validity of the hidden antigen
      approach is considered. Approaches to the problem of identifying hidden antigens
      are offered. The nature of the immune responses induced by injection of hidden
      antigens and their value in giving protection is considered in the light of the
      site of the hidden antigen in vivo. Particular attention is given to the value of
      integral membrane ectoenzymes as protective hidden antigens. The need to generate
      hidden antigens as recombinant proteins and the possibilities and problems
      associated with linear, conformational and carbohydrate epitopes are outlined.
      Finally, concerns about the lack of stimulation of induced immune responses and
      the risks of resistance developing are addressed.

PMID- 9184928
TI  - Excretory/secretory products of plerocercoids of Spirometra erinaceieuropaei
      induce the expression of inducible nitric oxide synthase mRNA in murine
      hepatocytes.
AB  - In this study, we observed the level of normal murine hepatocyte inducible NOS
      (iNOS) mRNA by semi-quantitative polymerase chain reaction (SQ-PCR) analysis
      after stimulation with ES products (ESP) and/or ESP fractions from the
      plerocercoids. We found that ESP are able to induce the expression of iNOS gene
      in a dose-dependent fashion. Treatment of ESP with polymyxin B did not affect
      their ability to induce the expression of iNOS gene, suggesting that bacterial
      lipopolysaccharide (LPS) is not involved. The iNOS-inducing factor (a) is
      soluble, and may be a component whose molecular mass exceeds 94 kDa as analyzed
      by a combination of SDS-PAGE and SQ-PCR. The peak of iNOS mRNA level was detected
      3 h after stimulation with ESP; the mRNA level decreased sharply from 9 h.
      Dexamethasone inhibited the induction of mRNA for hepatocyte iNOS. In contrast,
      cycloheximide stimulated the induction; this suggests that de nova protein
      synthesis is important in the regulation of the ESP-induced expression of iNOS
      mRNA. Actinomycin D blocked the induction. In addition, the results of Northern
      blot analysis showed that ESP suppressed the LPS (10 micrograms/ml) and
      interferon-gamma (IFN-gamma, 100 U/ml)-induced hepatocyte iNOS mRNA expression in
      a dose-dependent fashion and the suppressing effect was more marked when
      hepatocytes were exposed to ESP 3 h prior to LPS and IFN-gamma. These results
      demonstrate that the soluble factor(s) of ESP is capable of inducing murine iNOS
      gene expression in hepatocytes in the absence of added cytokines.

PMID- 9184929
TI  - Accumulation of Diplostomum spp. (Digenea: Diplostomatidae) metacercariae in the
      eyes of 0+ and 1+ roach (Rutilus rutilus).
AB  - Unlike other long-term studies of Diplostomum spp. metacercariae in fish eyes,
      this study investigated accumulation of the parasites in the eyes of very young
      roach for 3 consecutive years. Fish were caught by electro-fishing in the summers
      of 1990, 1991 and 1992 and the numbers of parasites located in the hosts eyes
      were recorded. Two distinct peaks of parasite abundance were observed, 1 in late
      June and the other in mid-September each year. Significantly, parasite abundance
      decreased after each of the peaks. Results obtained in a parallel investigation
      of the accumulation of the same parasites in rainbow trout in an adjacent fish
      farm showed the same 2 periods of accumulation each year. However, in the fish
      farm, no decrease in parasite abundance was observed at any time. The decreases
      in parasite abundance in the wild population can be attributed to mortality of
      the most heavily parasitized fish. As this did not occur in the farmed fish, in
      which similar levels of parasitism existed, it is likely that mortality in the
      wild population was an indirect result of the parasites.

PMID- 9184930
TI  - Schistosoma mansoni oviposition in vitro reflects worm fecundity in vivo:
      individual-, parasite age- and host-dependent variations.
AB  - In an attempt to determine whether in vitro oviposition of adult S. mansoni
      reflects the fecundity status of worms in vivo, Mongolian gerbils and ICR, BALB/c
      and SCID mice were infected with about 100 cercariae and examined on an
      individual basis, 5-12 weeks later, for worm burden, counts of eggs in liver and
      small intestine, and for the rate of egg deposition of ex-vivo female worms
      cultured in vitro, singly or in pairs, over a 3-5 day incubation period. The
      percentage of egg-laying female worms and the number of eggs laid/female after 3
      days in culture showed, like worm fecundity in vivo, wide inter-worm variability,
      especially in 5-, 6- and 12-week-old worms; varied significantly with the age of
      the parasite with a maximum level attained by worms of approximately 8 weeks of
      age; and differed in worms recovered from different host species and strains. The
      data taken together indicate that measuring the egg-producing ability of S.
      mansoni in vitro reflects the fecundity status of worms in vivo and additionally
      provides likely explanations for hitherto poorly understood findings on
      schistosome fecundity.

PMID- 9184931
TI  - Spermiogenesis and sperm ultrastructure in Troglocephalus rhinobatidis,
      Neoheterocotyle rhinobatidis and Merizocotyle australensis (Platyhelminthes,
      Monogenea, Monopisthocotylea, Monocotylidae).
AB  - The ultrastructural events of spermiogenesis and the ultrastructure of nature
      sperm of 3 species of monocotylid monogeneans are described. Two of these
      species, Troglocephalus rhinobatidis and Neoheterocotyle rhinobatidis are
      extremely similar in all the aspects studied, and their placement in separate
      subfamilies is questioned. Evidence is presented in both species for extensive
      distalward movement during spermiogenesis of an ornamented region associated with
      cortical microtubules, originally located in the zone of differentiation.
      Spermatids of Merizocotyle australis lack this ornamentation and the mature sperm
      also lacks cortical microtubules. Troglocephalus rhinobatidis exhibits the
      highest number (128) of spermatids in an isogenic group recorded for a flatworm
      to date. Sperm of all 3 species have 2 normal axonemes, shifted slightly relative
      to one another. Comparative data are presented on sperm and spermiogenesis of all
      monocotylids examined to date and the phylogenetic implications are discussed.

PMID- 9184932
TI  - An in vivo dose-response study of fenbendazole against Oesophagostomum dentatum
      and Oesophagostomum quadrispinulatum in pigs.
AB  - A dose-response study using fenbendazole (FBZ) was carried out in pigs infected
      with O. dentatum and O. quadrispinulatum to determine the minimum effective dose
      rate of the drug. Thirty pigs were randomly divided into 6 groups of 5 pigs and
      infected with 5000 infective larvae each. The animals were re-infected 5 days
      before treatment (Day 30 after the first infection) with the same number of
      larvae. On Day 35 the pigs in groups 1-5 were treated with FBZ at the following
      dose rates: 2.5 mg kg-1 (i.e. 50% of the registered dose level), 1.0 mg kg-1
      (20%), 0.25 mg kg-1 (5%), 0.1 mg kg-1 (2%) and 0.05 mg kg-1 (1%), respectively.
      Pigs in group 6 served as non-treated controls. Seven days after treatment (Day
      42 after infection) the pigs were slaughtered, worms recovered from the large
      intestine and counted. The species and sex of adult worms was determined. A high
      faecal egg count reduction (FECR) after treatment was observed in groups 1, 2 and
      3 (98%, 88% and 91%, respectively), while in groups 4 and 5 the egg counts were
      not affected by treatment. The mean worm count reduction was high in groups 1, 2
      and 3 (100%, 99.9% and 98.6%, respectively), but declined in groups 4 and 5 (77%
      and 40%, respectively). FBZ showed a high efficacy against immature worms in
      groups 1 and 2, while in groups 3, 4 and 5 counts were not reduced. Species
      differentiation revealed a higher effect of FBZ against O. dentatum than against
      O. quadrispinulatum. Sex differentiation indicated a slightly higher (not
      significant) efficacy against females than males in both species. This study
      demonstrated a high efficacy of FBZ against the nodular worms in pigs, even at 5%
      of the currently registered dose level.

PMID- 9184933
TI  - The death rate of Ostertagia circumcincta and Trichostrongylus colubriformis in
      lactating ewes: implications for anthelmintic resistance.
AB  - Lactating adult Romney ewes were infected, 4 weeks post-lambing, with
      benzimidazole (bz) resistant strains of Ostertagia circumcincta and
      Trichostrongylus colubriformis. Commencing 4 weeks after the initial infection
      the ewes were subjected to challenge 3 times weekly with 5000 L3 of bz
      susceptible strains of both parasite species. At weekly intervals over the
      following 6 weeks, groups of ewes were drenched with a bz anthelmintic
      (oxfendazole) to remove bz-susceptible parasites and slaughtered to determine
      adult worm burdens of the bz-resistant parasites. The O. circumcincta infection
      declined exponentially with a mean daily death rate of 10.6% day-1 and no worms
      were recovered after 4 weeks or more of challenge. The T. colubriformis infection
      did not decline significantly over the 6 weeks of continuous challenge,
      indicating that the death rate could not be distinguished from zero. The upper
      95% confidence limit for the death rate of T. colubriformis was 4.9%. The
      implications of these death rates on selection for drug resistance following ewe
      drenching during the post-partum period are discussed with selection pressure
      likely to be greater for T. colubriformis than for O. circumcincta.

PMID- 9184934
TI  - Characterization of secretory IgA responses in mice infected with Cryptosporidium
      parvum.
AB  - Mice inoculated at 5, 21 and 28 days of age with 10(6) or 10(7) Cryptosporidium
      parvum oocysts became infected but did not exhibit any clinical signs of disease.
      Specific IgA antibodies were detected in faecal extracts from all infected mice
      by an indirect immunofluorescent assay. These antibodies first appeared between
      11 and 37 days post-infection (dpi) and persisted until the end of the experiment
      at 55 dpl. They appeared earlier in older mice than in newborn mice. Reduction
      and resolution of oocyst shedding was not directly related, however, to IgA
      antibody levels in infected mice. Reactive C. parvum antigens were identified by
      immunoblotting techniques using faecal and serum samples from infected mice. IgA
      copro-antibodies reacted specifically with two antigens of 26 and 33 kDa, which
      were also identified by IgG antibodies in mouse serum. The role of these
      antibodies in the resolution of infections and the subsequent protection against
      challenge is unknown.

PMID- 9184935
TI  - A complementary DNA encoding an antigen from Trichinella spiralis muscle larvae
      and its analog from Trichinella T5 of bobcat origin: sequence, cloning and
      expressions.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR) was employed to amplify
      a cDNA encoding an excretory-secretory (ES) antigen with mol. wt 45-50 kDa by SDS
      PAGE from T. spiralis muscle larvae. The PCR product was purified by
      electrophoresis and sequenced by thermal cycle sequencing with primer walking.
      The cDNA is 890 bp long and encodes a polypeptide of 255 amino acid (AA)
      residues. Using the same methods, we also recovered a corresponding cDNA from
      Trichinella T5, which is 891 bp long and encodes 255 AAs. Comparison of the 2
      Trichinella species indicates approximately 2.6% and 2.4% differences between the
      2 cDNA sequences and between the 2 deduced AA sequences, respectively.

PMID- 9184936
TI  - The effect of fasting on Ascaris suum and Oesophagostomum spp. in growing pigs.
AB  - Experiments were conducted to study the possible influence of fasting on Ascaris
      suum and Oesophagostomum spp. In growing pigs. Forty young crossbred pigs
      naturally infected with A. suum and Oesophagostomum spp. were used. In one
      experiment 10 pigs were fasted and offered water ad libitum for 6 days, in
      another experiment for 10 days. Subsequently, these pigs, together with 10 non
      fasted control pigs per experiment were slaughtered, and worm numbers, worm
      location, sex, developmental stage and female worm fecundity were determined.
      Pigs fasted for 10 but not for 6 days had decreased numbers of A. suum and
      Oesophagostomum spp. at slaughter vs controls, and worms were found in more
      distal locations in the gastrointestinal tract. Fasting for both 6 and 10 days
      significantly lowered the fecundity of both worm species.

PMID- 9184937
TI  - The efficacy of ivermectin against laboratory strains of Heligmosomoides
      polygyrus (Nematoda).
AB  - A susceptible strain of Heligmosomoides polygyrus was selected for 15 generations
      with increasing doses of ivermectin (0-6 mg/kg). A passage strain was developed,
      parallel with the ivermectin-selected strain, to control for changes due to rapid
      passage from mouse to mouse. The LD50s of the 8th and 15th generations of the
      ivermectin-selected strain were 1.5 times that of the susceptible strain. The
      LD50 of the passage strain at generations 8 and 15 remained similar to that of
      the susceptible strain. Ivermectin efficacy was lower against the LA stage than
      against the adult stage in the susceptible strain, the Ivermectin-selected strain
      and the passage strain at generation 8.

PMID- 9184939
TI  - How safe are asexual blood-stage malaria vaccines?

PMID- 9184938
TI  - Lymphotropic antifilarial agents derived from closantel and chlorambucil.
AB  - New closantel and chlorambucil prodrugs expected to accumulate in the lymphatic
      system were evaluated on the filaria Molinema dessetae. The prodrugs of closantel
      had a delayed effect in vitro on the infective larvae compared to the free drug.
      The closantel prodrugs were less toxic in vivo than closantel itself. The most
      active prodrug after treatment at 200 mumol/kg by the oral route was the 1,3
      dipalmitoyl-2-succinyl-glycerol-closantel. The macrofilaricidal delayed effect of
      closantel prodrugs was of interest to prevent anaphylactic shock. In vitro,
      chlorambucil was active on M. dessetae infective larvae with an IC50 of 26
      microM. 1,3-Dipalmitoyl-2-chlorambucil-glycerol was slightly active while the
      addition of a thioether function between the drug and the lymphotropic ligand
      canceled the activity. However, no activity with chlorambucil and its prodrugs
      was observed in vivo. The lymphotropism of these prodrugs has now to be verified
      using comparative pharmacokinetics in serum and lymph to quantify the increase in
      drug concentration in lymph.

PMID- 9184940
TI  - Modelling of the 3-D structure of IFN-alpha-k and characterization of its surface
      molecular properties.
AB  - The 3-D structure of IFN-alpha-k (one of the alpha-interferon family) was
      constructed and optimized by molecular modelling starting from the X-ray
      structure of IFN-beta. The molecular surface of the optimized 3-D structure of
      IFN-alpha-k was then evaluated and characterized for its
      hydrophobicity/hydrophilicity. The structure of IFN-alpha-k was completed with
      its first segment (23 amino acid residues) called signal peptide. The 3-D
      structure of this segment was predicted to be in helical form bonded to the core
      by one loop. It was found that the complete structure of IFN-alpha-k can exist in
      at least two main conformations as far as the orientation of the signal peptide
      is concerned, i.e. in the open form (in which the signal peptide is directed
      outward of the 'body' of the molecule) and the closed form (where the signal
      peptide is aligned with the body). The relative stability of these forms strongly
      depends on the stabilization by the environment (e.g. by solvation) due to the
      prevailing hydrophilicity of the body and hydrophobic character of the signal
      peptide.

PMID- 9184941
TI  - Antiherpetic and anticoagulant properties of carrageenans from the red seaweed
      Gigartina skottsbergii and their cyclized derivatives: correlation between
      structure and biological activity.
AB  - The antiviral activity against herpes simplex virus types 1 and 2 of kappa/l-,
      partially cyclized mu/v-, and lambda-carrageenans isolated from the red seaweed
      Gigartina skottsbergii and their cyclized derivatives was analyzed. lambda
      Carrageenans and the partially cyclized mu/v-carrageenan were the most potent
      inhibitors of herpes viruses (including acyclovir-resistant variants and clinical
      isolates), with IC50 values lower than 1 microgram ml-1 against both serotypes
      and selectivity indices higher than 10(3). kappa/l-Carrageenans were slightly
      less effective than the other two types with IC50 values in the range 1.6-4.1
      micrograms ml-1. Antiherpetic activity was directly correlated to the amount of
      alpha-D-galactose 2,6-disulfate residues in the natural carrageenans. The
      cyclization of the alpha-D-galactose 6-sulfate and 2,6-disulfate units into 3,6
      anhydro-alpha-D-galactose and 3,6-anhydro-alpha-D-galactose 2-sulfate residues in
      these polysaccharides, in general, lowers the antiherpetic activity of the
      derivatives with respect to the natural carrageenans. Some carrageenans showed a
      very reduced anticoagulant activity only at concentrations that were considerably
      higher than the IC50, whereas others were totally devoid of anticoagulant
      properties. Among natural carrageenans, the mu/v-type IC3 shows the best
      relationship between antiviral efficacy and lack of anticoagulant action,
      resulting a very promising compound.

PMID- 9184942
TI  - FT-Raman studies on the transformation of G-actin to F-actin, the binding of
      cisplatin and transplatin to F-actin and the effects of the conformation of F
      actin.
AB  - The conformation change of G-actin of F-actin and the binding modes of cisplatin
      and transplatin to F-actin have been studied by FT-Raman spectroscopy. The
      studies show that the process of polymerization is related to the vibration of C
      S Gauche mode (approximately 650 cm-1), which indicates that the methionine (Met)
      contributes to the polymerization of actin. The relative intensity of
      I(925)/I(803), reflecting the conformation of actin secondary structure, does not
      change during the polymerization process. The effect of cisplatin and transplatin
      on F-actin is dependent on the species and their concentrations. Cisplatin, at
      high concentrations, affects the conformation of F-actin mainly by binding with
      the sulphur of methionine. Transplatin, even at low concentrations, obviously
      affects the F-actin's conformation due to it's multiple binding sites, on N
      containing sites in addition to S-methionine sites. These results relate to the
      differences in pharmacology and toxicology effects of the complexes.

PMID- 9184943
TI  - Secondary structure of T4 gene 33 protein. Fourier transform infrared and
      circular dichroic spectroscopic studies.
AB  - The secondary structure of bacteriophage T4 gene 33 protein (gp33) has been
      quantitatively examined by using Fourier transform infrared (FT-IR) and circular
      dichroism (CD) spectroscopy. Resolution enhancement techniques, including Fourier
      deconvolution and derivative spectroscopy were used to quantitate the spectral
      information from the amide I bands. The relative areas of these component bands
      indicate 21% alpha-helix, 25% beta-sheet, 34% turn, 12% random coil and 8% other
      undefined structures in gp33. An analysis of the CD spectrum of gp33 at the same
      pH and temperature revealed 19% alpha-helix, 25% beta-sheet, 13% turn and 43%
      random coil structures. The possible reasons for the discrepancies in estimates
      of the contributions to the secondary structure from turns and random coils are
      discussed.

PMID- 9184944
TI  - The role of the electrostatic coat in the formation of cholesteric liquid crystal
      spherulites from alpha-chitin.
AB  - The alpha-chitin used in the experiments came from crab shell waste. This was
      boiled in 3M HC1 to form a colloidal suspension of chitin crystallites. The
      electrostatic 'cost' surrounding the chitin was then manipulated in two ways. The
      first was the alteration of the pH of the chitin colloid (Chitin pKa = 6.1). This
      allowed the charge density on the crystalline rod of chitin to be altered. The
      second way was to alter the background charge in the environment by adding salt
      solutions to the colloid. The effect of the treatments was ascertained by
      measuring the diameter of the spherulites formed in vitro. These spherulites
      formed via self assembly through a liquid crystalline cholesteric phase. Raising
      the pH (within limits), resulted in larger spherulites. Raising the background
      charge also gave larger spherulites (within limits). As such both background
      charge and charge on the rod can be used to control the self assembly of the
      cholesteric spherulites. Manipulation of the electrostatic coat of the chitin
      could be a method of cellular remote control for formation of the helicoid in
      arthropod cuticle. This would allow the arthropods to set up conditions that aid
      the self assembly process.

PMID- 9184945
TI  - Solution conformation of alpha, beta or gamma-methylglutamyl-containing
      derivatives as probes of vitamin K-dependent carboxylase using molecular
      modelling and nuclear magnetic resonance.
AB  - In the present study, the conformational behaviour of methyl substituted N-BOC
      glutamic acid methyl esters (2M, 3T, 3E, 4T, 4E) has been completely
      characterized through combined NMR and molecular modeling studies. Hetero- and
      homonuclear coupling constants were measured in order to assign the remaining
      diastereotopic methylene protons at C(3) and/or C(4), and used for comparison
      with theoretical data. In parallel, the complete conformational analysis of these
      analogues has been achieved using molecular mechanics and molecular dynamics (MD)
      methods. The conformation of the glutamyl residue is established by the excellent
      agreement between the experimental and calculated side chain scalar coupling
      constants. The theoretical NMR data were calculated taking into account all the
      accessible conformations and using the averaging methods appropriate for internal
      motions. There is a significant influence of the methyl group on the
      conformational behaviour and on the biological relevance of these structures.
      Steric effect or electrostatic interaction may also have a considerable influence
      in stabilizing a conformational population in D2O solution. The conformational
      preferences of those different analogues in aqueous and methanol solution are
      discussed in the light of biological results obtained on the vitamin K-dependent
      carboxylase system.

PMID- 9184946
TI  - Dielectric relaxation of air-dried horn keratin.
AB  - Dielectric measurements as a function of temperature and frequency are reported
      for horn keratin. The measurements of dielectric constant epsilon' and loss
      factor epsilon", in keratin, were made in an electric field. This was done in the
      frequency range 10(1)-10(5) Hz and at temperatures from 22 to 220 degrees C. The
      samples contained 8% water by mass at room temperature at a relative humidity of
      40%. A remarkable dispersion observed in the range of lower frequencies was
      attributed to interfacial polarization. The temperature dependences of the
      dielectric constants of horn keratin revealed the occurrence of two main
      molecular processes. The first process corresponded to the removal of water in
      the temperature range 22-170 degrees C. The activation energy associated with the
      release of loosely and strongly bound water, was about 35 and 7 kcal/mol,
      respectively. The second process, above 170 degrees C, was related to the
      denaturation of the alpha-helical phase in keratin.

PMID- 9184947
TI  - Obstetrician-gynecologists and the public health.

PMID- 9184948
TI  - Motor vehicle crashes, pregnancy loss and preterm labor.
AB  - Trauma during pregnancy is remarkably common, and is greatly underestimated in
      terms of its contribution to both maternal and perinatal morbidity and mortality.
      Motor vehicle crashes, falls, assaults, including domestic violence, are all
      important mechanisms of injury, and clinical algorithms have been developed to
      manage the injured pregnant women. Focus on recognition and management of the
      most common injuries seen in pregnant women, namely abruptio placentae and
      uterine rupture are addressed through hemodynamic stabilization and continuous
      fetal and uterine contraction monitoring in the women injured beyond 24 weeks'
      gestation.

PMID- 9184949
TI  - The effect of grandmultiparity on chronic pelvic pain and sexual discomfort.
AB  - OBJECTIVES: To investigate the effect of grandmultiparity on chronic pelvic pain
      and sexual complaints. METHODS: 71 grandmultiparas and 65 non-grandmultiparas
      were interviewed. RESULTS: Pelvic pain, chronic pelvic pain and other pain
      compliants were significantly more frequent in grandmultiparas than non
      grandmultiparas (P < 0.001). Of the grandmultiparas, 94.4% had pelvic pain and
      81.7% had chronic pelvic pain. Coital complaints were observed in nearly half of
      both groups. CONCLUSION: Grandmultiparity has lasting reproductive health
      consequences in addition to its affect on obstetrical outcome and pelvic support.

PMID- 9184950
TI  - A comparative trial of labor induction with misoprostol versus oxytocin.
AB  - OBJECTIVE: To determine the efficacy and safety of intravaginal misoprostol
      compared with intravenous oxytocin in cervical ripening and labor induction.
      METHOD: The study was carried out at the Department of Obstetrics and Gynecology
      at the Hospital Loayza, Lima, Peru. The sample included 123 pregnant women with
      any indication for labor induction. The study was prospective and randomized. We
      compared the effect of 50 micrograms of intravaginal misoprostol administered
      every 4 h up to 600 micrograms with that observed using the standard protocol of
      oxytocin by continuous infusion. RESULTS: 57 patients with misoprostol (group 1)
      and 63 with oxytocin (group 2) were enrolled. Delivery occurred in 45 patients
      (78.9%) in group 1 and in 37 (58.7%) in group 2 (P < 0.017). Complications
      including tachysystole, uterine hypertony and hyperstimulation were higher in
      group 1, 21.1% than in group 2, 7.9% (P < 0.04). The incidence of cesarean
      section in both groups was similar to the overall incidence in our center. No
      differences were observed between groups in perinatal and postpartum adverse
      outcomes. The interval from start of induction to vaginal delivery was
      significantly shorter in the oxytocin group (8.4 +/- 4.1 vs. 11.3 +/- 6.9 h, P <
      0.005). CONCLUSION: Intravaginal administration of misoprostol is a safe and
      effective alternative for cervical ripening and labor induction. Maternal and
      neonatal complications did not increase significantly.

PMID- 9184951
TI  - Micronized flavonoid therapy in internal hemorrhoids of pregnancy.
AB  - OBJECTIVE: To assess the safety, efficacy and acceptability of a micronized
      flavonoid formulation in the treatment of internal hemorrhoids of pregnancy.
      METHODS: In an open study on hospital outpatients, we studied therapy with
      micronized diosmin 90% and hesperidin 10% for a median of 8 weeks before delivery
      and 4 weeks after delivery, in 50 women with acute hemorrhoids. The outcome
      measures were symptoms and signs of hemorrhoids; adverse effects; and
      acceptability of treatment. RESULT: On intention to treat analysis, 66% (95%
      confidence interval, range 79.1-52.9) had relief from acute symptoms by the 4th
      day; 53.6% (95% confidence interval, range 70-37.1, P < 0.001) fewer patients had
      relapse in the antenatal period. Treatment was well accepted, and did not affect
      pregnancy, fetal development, birth weight, infant growth and feeding.
      CONCLUSION: In the short term, micronized diosmin 90% and hesperidin 10% is safe,
      acceptable, and effective in the treatment of hemorrhoids of pregnancy.

PMID- 9184952
TI  - Interleukin-8 level in maternal serum as a marker for screening of histological
      chorioamnionitis at term.
AB  - OBJECTIVE: To establish a clinical method for immediate diagnosis of histological
      chorioamnionitis, by maternal blood sampling at term. METHOD: The sera of 22
      mothers with chorioamnionitis and 81 mothers without chorioamnionitis at term
      delivery were collected. The serum levels of cytokines including interleukin-1
      alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were titered and other
      conventional markers such as white blood cell and CRP were measured
      simultaneously. Chorioamnionitis was histopathologically confirmed after
      delivery. RESULT: The sera of mothers with histological chorioamnionitis showed a
      significant increase in IL-8 titer, but not in those of other cytokines or
      conventional markers, compared with those without chorioamnionitis. A positive
      correlation was observed between maternal and cord serum IL-8 levels. Maternal IL
      8 showed the highest predictive value for diagnosis of histological
      chorioamnionitis. CONCLUSION: Measurement of maternal IL-8 is useful for rapid
      prenatal screening of histological chorioamnionitis at term.

PMID- 9184953
TI  - Prediction of fetal lung maturity from near-infrared spectra of amniotic fluid.
AB  - OBJECTIVE: The aim of this study was to attempt to correlate the quantitative
      data obtained from the near-infrared (near-IR) spectra of amniotic fluid with the
      lecithin/sphingomyelin (L/S) ratio determined from thin layer chromatographic
      analysis on the same samples, in order to establish the feasibility of near-IR
      spectroscopy as an alternate method for the prediction of fetal lung development.
      METHODS: Samples of amniotic fluid were obtained by amniocentesis from 52
      patients between the 26th and 41st week of pregnancy. About 350 microliters of
      amniotic fluid was required to record the near-IR spectrum over the entire
      spectral range between 400 and 2500 nm using a commercial spectrometer. The L/S
      ratio was determined independently by thin layer chromatography (TLC) for each
      sample. For correlating the infrared spectra with the TLC-based L/S ratios, a
      partial least squares analysis was used. RESULTS: The L/S ratios predicted from
      the near-IR spectra of amniotic fluid were highly correlated and in excellent
      agreement with those determined by TLC (r = 0.91). CONCLUSION: Near-IR
      spectroscopy has the potential to become an alternate method to TLC for
      prediction of fetal pulmonary maturity.

PMID- 9184954
TI  - Vesicouterine fistula--an analysis of 24 cases from Poland.
AB  - OBJECTIVE: This study was undertaken to evaluate what clinical events or
      situations are currently associated with the occurrence of vesicouterine fistula.
      METHOD: A retrospective investigation was carried out on 24 patients treated in a
      tertiary referral center during a 12-year period. Clinical data were collected
      from the patients directly, the medical records, urographic and/or cystoscopic
      findings before repair and intraoperative findings at repair. RESULTS: All
      fistulas were iatrogenic, and 21 (87.5%) occurred following cesarean section or
      cesarean hysterectomy. Bladder injury occurred two times more often after repeat
      operations than after the primary. The proportion of repeat cesarean section
      resulting in a fistula was significantly increased (58.3% vs. 29.6%, P < 0.013)
      when compared to that previously reported. CONCLUSIONS: Cesarean sections are
      currently the single major risk factor associated with the occurrence of
      vesicouterine fistulas. Repeat procedures increase the risk of bladder injury and
      resultant fistulas.

PMID- 9184955
TI  - Ovarian metastasis from cervical carcinoma.
AB  - OBJECTIVE: To study the prognosis and metastatic route of cervical carcinoma with
      ovarian metastasis. METHOD: From 1980 to 1993, 10 of the 1507 patients with
      cervical carcinoma operated and who had ovarian metastasis were analyzed.
      RESULTS: Six patients had squamous cell carcinomas and 4 patients had
      adenocarcinomas. Their mean age was 45 years. Six of 9 patients undergoing pelvic
      lymphadenectomy had nodal metastasis. One patient did not have nodal dissection
      in the treatment course. Five of 10 patients had involvement of corpus: 3 were
      accompanied with nodal metastasis, 1 was not and 1 other was unknown. None of our
      cases survived more than 5 years. Their mean survival time was 20.8 months for
      squamous cell carcinomas and 29 months for adenocarcinomas. CONCLUSIONS: (1)
      Ovarian metastasis is histologically one of the ominous signs of cervical
      carcinomas regardless of stage. The prognosis of patients with ovarian metastasis
      from cervical squamous cell carcinoma from our data is not different from those
      from cervical adenocarcinoma. (2) Lymphatic spread and transtubal implantation
      are possible pathways of cervical cancer metastasizing to ovary, and involvement
      of the corpus may potentiate this mechanism.

PMID- 9184956
TI  - Significance and treatment of asymptomatic bacteriuria during pregnancy.

PMID- 9184957
TI  - Umbilical cord blood zinc levels in normal and pathological pregnancies.

PMID- 9184959
TI  - Recurrent molar pregnancy.

PMID- 9184958
TI  - Interval female sterilization of HIV-1 positive women: laparoscopy versus
      minilaparotomy.

PMID- 9184960
TI  - Ruptured isthmal pregnancy following laparoscopic salpingostomy in the
      ipsilateral tube.

PMID- 9184961
TI  - Genital tract tuberculosis with myometrial involvement.

PMID- 9184962
TI  - Expectations and fears of women regarding two methods of prenatal screening.

PMID- 9184963
TI  - Anterior uterine incarceration.

PMID- 9184964
TI  - Placenta accreta associated with rupture of a rudimentary horn pregnancy.

PMID- 9184965
TI  - Severe fetal thrombocytopenia diagnosed during labor.

PMID- 9184966
TI  - Role of ELISA (enzyme-linked immunosorbent assay) in genital tuberculosis.

PMID- 9184967
TI  - Transvaginal uterine morcellation with unsuspected adenocarcinoma of the
      endometrium.

PMID- 9184968
TI  - ACOG educational bulletin. Thromboembolism in pregnancy. Number 234, March 1997.
      American College of Obstetricians and Gynecologists.

PMID- 9184969
TI  - ACOG educational bulletin. Hemorrhagic shock. Number 235, April 1997 (replaces
      no. 82, December 1984). American College of Obstetricians and Gynecologists.

PMID- 9184970
TI  - ACOG committee opinion. New ultrasound output display standard. Number 180,
      November 1996. Committee on Obstetric Practice. American College of Obstetricians
      and Gynecologists.

PMID- 9184971
TI  - ACOG criteria set. Ambulatory care sensitive indicator: ectopic pregnancy,
      ruptured. Number 21, December 1996. Committee on Quality Assessment. American
      College of Obstetricians and Gynecologists.

PMID- 9184972
TI  - ACOG criteria set. Ambulatory care criteria set: hypoestrogenism. Number 22,
      April 1997. Committee on Quality Assessment. American College of Obstetricians
      and Gynecologists.

PMID- 9184974
TI  - Transnasal endoscopic management of choanal atresia.
AB  - Since 1755, when Roederer first described choanal atresia, more than 350 papers
      have been published dealing with the various aspects of this entity. Many
      surgical techniques have been used to treat the malformation, each with its
      advantages and disadvantages. Endoscopic transnasal repair of choanal atresia
      provides excellent visualization and enables accurate surgery to be performed on
      patients of all ages and even on newborn infants. Described are two newborn
      infants, one with bilateral choanal atresia and the other with bilateral choanal
      stenosis, successfully treated by endoscopic transnasal repair, with a 12 month
      follow-up. The technique of endoscopic choanal repair is described, emphasizing
      it as a highly successful, short and safe procedure with swift recovery and short
      hospitalization.

PMID- 9184975
TI  - Nasal mucociliary transport and ciliary ultrastructure in cystic fibrosis. A
      comparative study with healthy volunteers.
AB  - Cystic fibrosis (CF) is a deadly hereditary disease that produces an abnormally
      thick, viscous and abundant secretion in the respiratory tract. This secretion in
      turn leads to the development of recurrent respiratory infections and
      irreversible lung damage. We have studied nasal mucociliary transport by means of
      an isotopic technique in 12 patients with CF and in 12 healthy volunteers. Nasal
      mucociliary transport was repeated at 12-18 months in the patients. In five
      randomly selected patients ciliary ultrastructure was studied. The velocity of
      nasal mucociliary transport was significantly slower than in healthy persons (P <
      0.001) and no significant differences were observed in both studies (P < 0.05).
      No significant differences were either observed in the CF group between the homo-
      and heterozygotes (P < 0.5), or in those six patients infected by Pseudomonas
      aeruginosa (P < 0.05). Ciliary ultrastructure was normal in one patient. In
      another patient the sample showed no cilia, while the remaining three exhibited
      changes similar to those observed in chronic respiratory infections:
      supernumerary peripheral tubules, ciliary disorientation and ciliary complexes.

PMID- 9184973
TI  - Childhood hearing loss in sub-Saharan Africa: a review and recommendations.
AB  - Nearly 10% of the world's population lives in sub-Saharan Africa, a region
      comprised of many countries with least developed nation status. The region has a
      predominantly young population and many children in the region are at risk of
      pathologies associated with hearing loss. Despite the constraints associated with
      low socioeconomic levels, a number of valuable studies have been carried out into
      the prevalence and etiology of childhood hearing loss in the sub-Saharan region.
      A review of the published literature related to childhood hearing loss in sub
      Saharan Africa is presented and recommendations made on possible future research
      directions that could assist hearing loss prevention and management.

PMID- 9184976
TI  - Erbe constant voltage electrocautery versus conventional variable voltage
      electrocautery for tonsillectomy in children.
AB  - This prospective, randomized study was performed to compare postoperative pain,
      blood loss, and procedure time using the Erbe electrocautery device and
      conventional electrocautery. The Erbe device differs from conventional cautery
      devices in that it produces constant voltage and variable wattage whereas
      conventional devices produce variable voltage and constant wattage. This means
      that the conventional devices allow voltage surges and constant wattage no matter
      what type of tissue is encountered. The Erbe device has the inherent capability
      to maintain constant voltage, i.e. no surging as well as varying wattage
      according to tissue resistance. This, in theory, allows the Erbe device to impose
      less tissue damage and, theoretically, less postoperative pain. Fifty-seven
      patients 5-21 years of age who were scheduled for adenotonsillectomy were
      enrolled in the study. Results indicated less postoperative pain, although blood
      loss appeared to be increased compared to conventional electrocautery. The Erbe
      electrocautery device appears to be a viable device to perform tonsillectomy in
      children.

PMID- 9184977
TI  - Patterns of Kawasaki syndrome presentation.
AB  - Kawasaki syndrome (KS) is a systemic disorder of unknown etiology that can lead
      to coronary artery aneurysm and thrombosis in a significant number of children.
      It is defined by a number of clinical guidelines set by the Centers for Disease
      Control (Rauch, A.M., Hurwitz, E.S. (1985) Centers for Disease Control (CDC).
      Case Definition for Kawasaki syndrome. Pediatr. Infect. Dis. 4, 702-703). Many of
      the symptoms of this illness may lead the patient to the otolaryngologist. These
      criteria include injected or fissured lips, injected pharynx, strawberry tongue
      and cervical lymphadenopathy. When administered in the first 10 days of the
      illness, gamma globulin has been demonstrated to reduce the prevalence of
      coronary artery abnormalities (Newburger, J.W., Takahashi, M., Burns, J.C. et al.
      (1986) Treatment of Kawasaki syndrome with intravenous gamma globulin. N. Engl.
      J. Med. 315, 341-347). Unfortunately, when a diagnosis of KS is not considered or
      if a patient presents with unusual symptoms that are not consistent with the CDC
      guidelines, the diagnosis and treatment of KS can be delayed or even missed. We
      present a series of patients with KS to illustrate its patterns of presentation.

PMID- 9184978
TI  - Incidence of dehiscences in the fallopian canal.
AB  - Fifty human temporal bones from necropsies were used to study the frequency of
      canal dehiscences in detail along the course of the facial nerve. Specifically,
      the study focused on bony dehiscences in the fallopian canal and vascular
      communications between the facial nerve and the surrounding bone. High frequency
      of dehiscences at the oval window (60%) and in the pyramidal segment (54%) were
      found. These dehiscence rates are in agreement with published reports. A 20% rate
      of dehiscences at the most anterior segment of the tympanic segment was noted and
      a non-reported high rate (20%) of multiple dehiscences along the course of the
      fallopian canal in the same temporal bone in specimens of newborns and young
      children. The significance of these findings in terms of clinical implications is
      discussed.

PMID- 9184979
TI  - Importance of mastoid pneumatization on secretory otitis media.
AB  - Secretory otitis media is the most common middle ear disease of childhood. It
      heals spontaneously, by medical therapy or by minor surgical procedures in most
      of the cases. Sequelae such as retraction pockets and adhesive otitis that lead
      to cholesteatoma rarely occur, but initially it is hard to diagnose which patient
      will acquire a sequela. It is well known that mastoid pneumatization is poor in
      the patients who had complications like retraction pocket, adhesive otitis and
      cholesterol granuloma. The aim of this study was to determine if any relationship
      exists between mastoid pneumatization and secretory otitis media. Lateral mastoid
      X-rays of 47 children with secretory otitis media were evaluated. After 2 months
      of follow-up with medical therapy, 30 of the 47 patients needed ventilation tube
      insertion. The remaining 17 patients showed total recovery with medicines only.
      Control X-rays of the operated patients were taken 6 months after the operation.
      Mastoid pneumatizations of patients healed with medicine were compared with the
      operated patients. There were statistically significant differences between the
      mastoid pneumatizations of surgically and medically treated groups. In addition
      we observed a statistically significant difference between the mastoid areas of
      the preoperative and the postoperative X-rays. We concluded that mastoid
      pneumatization might be considered as a prognostic indicator in secretory otitis
      media. The estimated prognosis is poor when the mastoid pneumatization is poor.

PMID- 9184980
TI  - Hemangioendothelioma of the temporal bone in a child.
AB  - Hemangioendothelioma is a vascular tumor of endothelial cell origin. It may
      involve bone or soft tissues and can behave like a benign or a malignant tumor.
      In the literature there are several case reports on the involvement of the head
      and neck region, but only three cases of temporal bone involvement, all of them
      in adults. A 3-year-old child, complaining of left retro-auricular swelling and
      tenderness, was found to be suffering from hemangioendothelioma of the temporal
      bone. Doppler ultrasound and CT scan showed a highly vascular mass with bone
      destruction. Wide surgical excision was recommended, but rejected by the parents,
      nor did they agree to treatment with alpha-interferon. The child did not return
      for any further treatment.

PMID- 9184981
TI  - Maturation of otoacoustic emissions: longitudinal versus cross-sectional study.

PMID- 9184982
TI  - Distribution and substrate properties of agrin, a heparan sulfate proteoglycan of
      developing axonal pathways.
AB  - The distribution and substrate properties of agrin, an extracellular matrix
      heparan sulfate proteoglycan (HSPG), was investigated in the developing chick
      nervous system by immunocytochemistry, Western blotting, and in neurite outgrowth
      assays. By comparing the distribution of agrin with that of laminin-1, merosin
      (laminin-2), neurofilament, and neural cell adhesion molecule (NCAM), it was
      found that throughout development, agrin is a constituent of all basal laminae.
      From embryonic day (E) 4 onwards, agrin is also abundant in axonal pathways of
      the central nervous system, such as the optic nerve, the tectobulbar pathway, the
      white matter of the spinal cord, and the marginal and the molecular layers of the
      forebrain and the cerebellum. The abundance of agrin in brain decreases from E13
      onwards. In the peripheral nervous system, agrin is present throughout
      development as a constituent of the Schwann cell basal laminae. Western blots
      confirmed the immunocytochemical data, showing maximum expression of agrin occurs
      during the early to medium stages of brain development. Western blots also showed
      that in mouse and human brain, agrin exists as an HSPG. Purified agrin did not
      support neurite outgrowth, rather it inhibited retinal neurite extension on mixed
      agrin/merosin substrates. Despite the fact that agrin, when used as a substrate
      inhibited neurite outgrowth, its temporal and spatial overlap with growing axons
      suggests that agrin has a supportive role in the development of axonal pathways,
      possibly as a binding component for growth factors and cell adhesion proteins.

PMID- 9184983
TI  - Afferent and efferent connections of the diencephalic prepacemaker nucleus in the
      weakly electric fish, Eigenmannia virescens: interactions between the
      electromotor system and the neuroendocrine axis.
AB  - The afferent and efferent connections of the gymnotiform central posterior
      nucleus of the dorsal thalamus and prepacemaker nucleus (CP/PPn) were examined by
      retrograde and anterograde transport of the small molecular weight tracer,
      Neurobiotin. The CP/PPn was identified by physiological assay and received a
      local iontophoretic injection of Neurobiotin. Retrogradely labeled somata were
      observed in the ventral telencephalon, hypothalamus, and the pretectal nucleus
      electrosensorius. Anterogradely labeled fibers were traced from the CP/PPn to the
      ventral telencephalon, the hypothalamus, the neuropil immediately adjacent to the
      most rostral subdivision of the nucleus electrosensorius, the optic tectum, and
      the pacemaker nucleus. Retrograde transport of tracer following injections into
      the ventral telencephalon, preoptic area, lateral hypothalamus, tectum, and
      pacemaker nucleus confirmed these efferent targets. A rostromedial subarea of the
      CP/PPn can be identified that projects to basal forebrain regions and to a
      lateral region of the CP/PPn that contains afferents to the pacemaker. Many of
      the targets, which are connected with the CP/PPn, have been linked to
      reproductive behavior or neuroendocrine control in other fishes. A comparative
      analysis reveals that the efferent pathways of the CP/PPn appear similar and may
      be homologous to efferent pathways of some components of the auditory thalamus
      among tetrapods.

PMID- 9184984
TI  - gamma-Aminobutyric acid receptor distribution in the mushroom bodies of a fly
      (Calliphora erythrocephala): a functional subdivision of Kenyon cells?
AB  - Antibodies against the Drosophila gamma-aminobutyric acid (GABA) receptor subunit
      RDL were used to investigate the significance of inhibitory inputs to the
      mushroom bodies in the blowfly (Calliphora erythrocephala) brain. The pedunculus
      and the lobes of the mushroom body, which mainly consist of Kenyon cell fibers,
      revealed strong immunoreactivity against RDL. Pedunculi, alpha- and beta-lobe
      show characteristic unstained core structures with concentric labeling along the
      neuropile axis. The gamma-lobes in contrast exhibit a compartmentalized RDL
      immunoreactive pattern. These data suggest an important role of GABAergic
      inhibition in the pedunculus and the lobes of insect mushroom bodies. It is most
      likely that the RDL-immunoreactivity in the mushroom bodies is closely related to
      Kenyon cell fibers suggesting that Kenyon cells are an inhomogeneous class of
      neurons, only part of which receive inhibitory GABAergic input from extrinsic
      elements. GABAergic inhibition, therefore, may play a substantial role in the
      process of learning and memory formation in the insect mushroom bodies.

PMID- 9184985
TI  - Cone photoreceptor topography in the retina of sexually mature Pacific salmonid
      fishes.
AB  - We examined the retinal cone topography in sexually mature individuals from four
      species of Pacific salmonid fishes by using semithin plastic sections. We
      identified variations in cone density and cone arrangements and noted the
      presence of putative ultraviolet (UV) cones. Putative UV cones were found over an
      area extending dorsotemporally from the center of the retina. Because most of the
      putative UV cones are believed to disappear in early ontogeny, their presence
      over a large proportion (15-20%) of the surface area of the adult retina suggests
      that they may be reincorporated prior to or at sexual maturity, at least in
      rainbow trout. Cone density varied across the retina, with highest values at the
      peripheral margin. Relatively high densities were observed ventrotemporally (in
      all specimens) and, to a lesser extent, dorsonasally (7 of 11 specimens). The
      higher cone density in the ventrotemporal retina may represent a retinal
      specialization in the part of the visual field located above and in front of the
      animal. Lowest cone densities were found dorsocentrally and coincided
      approximately with the distribution of putative UV cones, raising the possibility
      that these cones may not be used in visual tasks requiring the higher visual
      acuity normally associated with higher cone densities. We also report a novel
      cone arrangement that consists of rows of double cones inserted between rows
      composed of single-double cone pairs alternating in position.

PMID- 9184986
TI  - Sympathetic axons invade the brains of mice overexpressing nerve growth factor.
AB  - Transgenic mice that overexpress nerve growth factor (NGF) in cells producing
      glial fibrillary acidic protein were used to determine whether sympathetic axons
      will invade the undamaged, postnatal mammalian brain. By using reverse
      transcriptase-polymerase chain reaction, NGF mRNA transgene expression was
      detectable in the hippocampi and cerebella of transgenic mice but not in age
      matched, wild type mice. Elevated levels of NGF protein were detected in the
      hippocampi and cerebella of postnatal and adult transgenic animals as well as in
      conditioned media from transgenic cerebellar astrocytes in culture. The brains of
      these transgenic mice were found to contain postganglionic sympathetic fibers, as
      identified by their immunohistochemical staining for tyrosine hydroxylase and by
      their disappearance following superior cervical ganglionectomy. In the
      cerebellum, a robust plexus of sympathetic fibers was evident in the deep white
      matter and in the inferior cerebellar peduncles. These axons within the
      cerebellum were observed as early as 14 days after birth and dramatically
      increased in number with age. Sympathetic axons were also associated with the
      large blood vessels of the hippocampal fissure and were present within the hilar
      region of the dentate gyrus. NGF immunoreactivity was present within the
      sympathetic axons as well as within glial cells in the transgenic cerebellum and
      hippocampus. Wild type mice, however, lacked similar patterns of immunostaining.
      These results demonstrate that elevated expression of NGF in the intact mammalian
      brain results in the growth of sympathetic axons into the central nervous system
      in the absence of injury.

PMID- 9184987
TI  - Development of MK-801, kainate, AMPA, and muscimol binding sites and the effect
      of dark rearing in rat visual cortex.
AB  - We used quantitative autoradiography to determine whether the development of
      glutamate receptors correlates with the plastic period for monocular deprivation
      in rat visual cortex. To study glutamate receptors, we incubated sections of rat
      visual cortex with tritiated (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]
      cyclohepten-5,10imin e maleate (MK-801), tritiated kainate, and tritiated amino-3
      hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). [3H]MK-801 is a
      noncompetitive ligand for the N-methyl-D-aspartate (NMDA) receptor. [3H]kainate
      and [3H]AMPA are competitive ligands for non-NMDA receptors. To compare glutamate
      binding sites with a nonglutamate binding site, we studied [3H]muscimol, which
      binds to gamma-aminobutyric acid (GABA)A receptors. [3H]MK-801 binding was
      maximal at postnatal day 26 (P26) and decreased in adulthood. [3H]AMPA binding
      was maximal at P18. [3H]kainate binding and [3H]muscimol binding were not age
      dependent. Dark rearing partially prevented the age-dependent decrease in [3H]MK
      801 binding but had no effect on [3H]kainate or [3H]AMPA binding. Dark rearing
      decreased muscimol binding in adult animals. These results suggest that NMDA
      receptors, but not other glutamate receptors or GABAA receptors, are likely to be
      critical for developmental plasticity in rat visual cortex.

PMID- 9184988
TI  - Galanin-immunoreactive synaptic terminals on basal forebrain cholinergic neurons
      in the rat.
AB  - Previous studies have indicated that galanin is one of the most abundant peptides
      in the basal forebrain and that it has a significant modulatory influence on
      cholinergic transmission. The aim of the present study was to use a light
      electron microscopic correlation technique to determine whether galanin
      immunoreactive terminals form synaptic contacts with basal forebrain cholinergic
      cells of the rat. Sections from fixed-perfused brains were stained at the light
      and electron microscopic levels for galanin and choline acetyltransferase
      immunoreactivity in the same section by using a dual-colour immunohistochemical
      method. The results showed that galanin-immunoreactive axonal terminals are
      unevenly distributed in the medial septal nucleus, the diagonal band, and the
      nucleus basalis. Galanin-positive synapses were most prominent on choline
      acetyltransferase-positive neurons in the lateral parts of the nucleus of the
      diagonal band and in the posterior half of the nucleus basalis, which is where
      there was the greatest overlap between the distribution of galanin-immunoreactive
      terminals and choline acetyltransferase-positive neurons. The origins of these
      galanin-positive terminals are not known, but the results confirm that the basal
      forebrain galaninergic system has a synaptic influence on basal forebrain
      cholinergic neurons in the rat.

PMID- 9184989
TI  - Organization of the descending projections from the parabrachial nucleus to the
      trigeminal sensory nuclear complex and spinal dorsal horn in the rat.
AB  - To clarify direct descending projections from the parabrachial nucleus (PB) to
      the trigeminal sensory nuclear complex (TSNC) and spinal dorsal horn (SpDH), the
      origin and termination of descending tract cells were examined by the anterograde
      and retrograde transport methods. Phaseolus vulgaris leucoagglutinin (PHA-L) and
      Fluorogold (FG) or dextran-tetramethylrhodamine (Rho) were used as neuronal
      tracers for the anterograde and retrograde transport, respectively. The
      ventrolateral PB, including Kolliker-Fuse nucleus (KF), sent axons terminating
      mainly in the ventrolateral parts of rostral trigeminal nuclei of the principalis
      (Vp), oralis (Vo), and interpolaris (Vi) as well as in the inner lamina II of the
      medullary (nucleus caudalis, Vc) and SpDH. Although the descending projections
      were bilateral with an ipsilateral dominance, TSNC received a more dominant
      ipsilateral projection than SpDH. The cells of origin of the descending tracts
      were located mainly in KF, but TSNC received fewer projections from the KF than
      SpDH. Namely, TSNC received a considerable projection from the medial subnucleus
      of PB and the ventral parts of lateral subnuclei of PB, such as the central
      lateral subnucleus and lateral crescent area. The other difference noted between
      TSNC and SpDH was that the former received projections mainly from the caudal two
      thirds of KF and the latter from the rostral two thirds of KF. These results
      demonstrate the existence of direct parabrachial projections to TSNC and SpDH
      that are organized in a distinct manner and suggest that both pathways are
      involved in the control of nociception.

PMID- 9184990
TI  - Calretinin expression in the chick brainstem auditory nuclei develops and is
      maintained independently of cochlear nerve input.
AB  - The expression of the calcium-binding protein calretinin (CR) in the chick
      brainstem auditory nuclei angularis (NA), laminaris (NL), and magnocelularis (NM)
      was studied during normal development and after deafening by surgical removal of
      the otocyst (embryonic precursor of the inner ear) or columella (middle ear
      ossicle). CR mRNA was localized by in situ hybridization by using a radiolabeled
      oligonucleotide chick CR probe. CR immunoreactivity (CR-IR) was localized on
      adjacent tissue sections. CR mRNA signal in the auditory nuclei was expressed at
      comparable levels at embryonic day (E)9 and E11 and increased thereafter to reach
      the highest levels in posthatch chicks. CR-IR neurons were apparent in NM and NA
      at E11 and in NL by E13, and CR-IR increased in all three auditory nuclei
      thereafter. Neither unilateral nor bilateral otocyst removal caused detectable
      changes in the intensity of CR mRNA expression or CR-IR in the auditory nuclei at
      any of the several ages examined. Similarly, columella removal at posthatching
      day 2 or 3 failed to significantly affect CR mRNA or CR-IR levels at 3 hours, 1
      day, or 3-4 days survival times. We conclude that cochlear nerve input is not
      necessary for expression of either calretinin mRNA or protein and that the
      profound decrease in sound-evoked activity caused by columella removal does not
      affect the maintenance of CR expression after hatching.

PMID- 9184991
TI  - Biogenesis of surface domains in fly photoreceptor cells: fine-structural
      analysis of the plasma membrane and immunolocalization of Na+, K+ ATPase and
      alpha-spectrin during cell differentiation.
AB  - Electron microscopic examination of pupal and adult blowfly (Calliphora
      erythrocephala) retina provides novel details on the biogenesis of the
      photoreceptor surface, particularly regarding the development of the microvillar
      rhabdomere and associated structures, such as the submicrovillar endoplasmic
      reticulum. Localization of the Na+, K(+)-ATPase on the surface of developing
      photoreceptors has also been examined by immunofluorescence confocal microscopy
      and immunogold electron microscopy. Na+, K(+)-ATPase has a nonpolarized
      distribution in midpupal photoreceptors that are determined by fate but that are
      not yet completely differentiated. Large amounts of Na+, K(+)-ATPase are
      synthesized and delivered to the cell surface throughout the second half of pupal
      life. At certain time points in late pupal development, specific membrane domains
      become cleared of Na+, K(+)-ATPase in the photoreceptors R1-R6. However, the
      distribution of Na+, K(+)-ATPase remains nonpolarized in R7/R8, even after
      eclosion. Because the membrane-associated cytoskeleton plays a direct role in the
      establishment and maintenance of membrane domains in a variety of systems, it is
      of interest to study the distribution of alpha-spectrin and its possible
      association with Na+, K(+)-ATPase. The localization of alpha-spectrin resembles
      the distribution pattern of Na+, K(+)-ATPase in midpupal and adult
      photoreceptors. However, changes in Na+, K(+)-ATPase localization in late pupal
      photoreceptors precede the redistribution of alpha-spectrin by several days.
      Biochemical studies of cellular membranes demonstrate further that Na+, K(+)
      ATPase can be solubilized by Triton X-100, although alpha-spectrin remains in a
      macromolecular complex. These results indicate that the development and the
      maintenance of the polarized Na+, K(+)-ATPase distribution in blowfly
      photoreceptors are not tightly coupled to alpha-spectrin.

PMID- 9184992
TI  - Differential number of glycine- and GABA-immunopositive neurons and terminals in
      the deep cerebellar nuclei of normal and Purkinje cell degeneration mutant mice.
AB  - The total number of glycine-immunopositive (Gly+) neurons in the deep cerebellar
      nuclei (DCN) was quantified under normal conditions in wild-types (B6C3Fe) and
      compared with the Purkinje cell-deprived situation in Purkinje cell degeneration
      (PCD)-mutants by using an unbiased stereological method, the disector. In
      addition, the size and density of Gly+ terminals, the number of gamma
      aminobutyric acid immunopositive (GABA+) somata and the somatal colocalization of
      Gly and GABA were determined. In both wild-types and PCD mutants, Gly+ somata are
      distributed relatively homogeneously among the different subdivisions of the DCN.
      However, in the complete volume of the DCN, which is reduced in PCD mutants by
      52%, 8,582 Gly+ neuronal somata are present in wild-types and 14,637 in PCD
      mutants, which corresponds to an increase of 70.5% in the mutant. In contrast,
      the total number of GABA+ somata is almost the same in wild-types (16,713) and in
      PCD mutants (15,339). The number of neurons that colocalize both Gly and GABA is
      again almost identical in wild-types (3,976) and PCD mutants (3,861). Moreover,
      the size and number of Gly+ terminals contacting DCN neurons of PCD mutants are
      increased significantly compared to the wild-types. These data define for the
      first time the normal distribution of glycine and its somatal colocalization with
      GABA in the DCN of the mouse. In addition, it is shown that the Purkinje cell
      loss in PCD mutants leads to a significant increase in Gly+ somata and to a
      larger size and number of Gly+ boutons in the DCN. This suggests that the
      respective neurons are capable of exerting an enhanced inhibitory synaptic
      activity on their target neurons, substituting, at least in part, for the lost
      Purkinje cell (PC) inhibition. Probable correlations of these findings with the
      mildness of the motor disturbances found in PCD mutants are discussed.

PMID- 9184993
TI  - Embryogenesis of the phrenic nerve and diaphragm in the fetal rat.
AB  - The embryogenesis of the mammalian phrenic nerve and diaphragm continues to be
      poorly understood. The purpose of this study was to reexamine this general issue
      and resolve some long-standing controversies. Specifically, we examined 1) the
      migratory path and the initial target for phrenic axons; 2) the relationship
      between the phrenic nerve and the primordial diaphragm during descent from the
      cervical to the thoracic spinal cord levels; and 3) the nature of the interaction
      between the progression of phrenic nerve intramuscular branching, myoblast and/or
      myogenic cell migration, and diaphragmatic myotube formation. We demonstrate that
      a leading group of "pioneering" phrenic axons migrate along a well-defined track
      of neural cell adhesion molecule (NCAM)-expressing and low-affinity nerve growth
      factor (p75) receptor-expressing cells to reach the primordial diaphragm, the
      pleuroperitoneal fold, at embryonic day (E) 13. During the next day of
      development, the phrenic nerve and the primordial diaphragm descend together
      toward the level of the thoracic spinal cord. By E14.5, intramuscular branching
      has commenced. There is a tight spatiotemporal correlation between the outgrowth
      of intramuscular phrenic nerve branches, the distribution of myoblasts and/or
      myogenic cells, and the formation of myotubes within the developing diaphragm,
      implicating intimate mutual regulation.

PMID- 9184994
TI  - Development of phrenic motoneuron morphology in the fetal rat.
AB  - This study examined the morphological changes that a homogeneous mammalian spinal
      motoneuron population undergoes during foetal development. Retrograde labelling
      of the phrenic nerve with the carbocyanine dye, DiI, was used to visualise
      developmental changes in phrenic motoneuron morphology within the cervical spinal
      cord of perinatal rats from embryonic day (E) 13.5 to birth (ca. E21). Groups of
      intimately associated phrenic somata had migrated into the ventromedial region of
      cervical segments C3-C6 by E14. This migration was followed by their progressive
      compaction into a tightly aligned column by E18. During this period, close
      contact was maintained between phrenic somata throughout the motor pool,
      suggestive of the presence of gap junctions. From E15 to E18, extensive dendritic
      arborisations fanned out dorsolaterally and ventromedially into the white matter
      and the floor plate. By E19, however, dendritic fasciculation and retraction and
      the extension of newly formed rostrocaudally projecting dendrites had resulted in
      the approximation of the dendritic morphology observed at birth. These data
      demonstrate that morphological maturation of phrenic motoneurons occurs
      subsequently to the onset of functional recruitment and the arrival of central
      processes of dorsal root ganglion neurons within the ventral horn (ca. E17). By
      birth, a number of immature features remain, including a larger proportion of
      neurites that project into the white matter and into the floor plate, the
      presence of growth cones on a number of dendrites, and close contact between
      populations of contralaterally derived dendrites.

PMID- 9184995
TI  - Differences of the primate flocculus and ventral paraflocculus in the mossy and
      climbing fiber input organization.
AB  - Potential sources of cerebellar cortical afferent fibers were identified in the
      vestibular ganglion, medulla oblongata, pons, and cerebellar nucleus of seven
      anesthetized Macaca fuscata after local injections of wheat germ agglutinin
      conjugated horseradish peroxidase or Fast Blue into the flocculus (FL) or ventral
      paraflocculus (VP). There were differences in the sources of mossy fibers to the
      FL and VP. Labeled neurons, after injections into the FL, were located mainly in
      the ipsilateral vestibular ganglion, bilaterally in the vestibular and prepositus
      hypoglossal nuclei, nucleus reticularis tegmenti pontis, and the central part of
      the mesencephalic reticular formation including the raphe nuclei. Labeled neurons
      were rarely seen in the pontine nuclei after injections into the FL. By contrast,
      after injections into the VP, numerous labeled neurons were located in the
      contralateral pontine nuclei, but relatively few in the vestibular nuclei
      bilaterally. Sources of climbing fibers to the FL and VP were completely
      contralateral to the injection side. After the injection into the FL and VP,
      labeled neurons were located in the dorsal cap, ventrolateral outgrowth, and
      ventral part of the medial accessory olivary nucleus. The projections from these
      three olivary areas were generally consistent with a zonal pattern of
      terminations in the FL and VP. The present results are consistent with a
      hypothesis that the FL is mainly involved in the control of vestibulo-ocular
      reflex and that the VP is mainly involved in the control of smooth pursuit eye
      movements.

PMID- 9184996
TI  - Distribution of choline acetyltransferase immunoreactivity in the brain of anuran
      (Rana perezi, Xenopus laevis) and urodele (Pleurodeles waltl) amphibians.
AB  - Because our knowledge of cholinergic systems in the brains of amphibians is
      limited, the present study aimed to provide detailed information on the
      distribution of cholinergic cell bodies and fibers as revealed by
      immunohistochemistry with antibodies directed against the enzyme choline
      acetyltransferase (ChAT). To determine general and derived features of the
      cholinergic systems within the class of Amphibia, both anuran (Rana perezi,
      Xenopus laevis) and urodele (Pleurodeles waltl) amphibians were studied. Distinct
      groups of ChAT-immunoreactive cell bodies were observed in the basal
      telencephalon, hypothalamus, habenula, isthmic nucleus, isthmic reticular
      formation, cranial nerve motor nuclei, and spinal cord. Prominent plexuses of
      cholinergic fibers were found in the olfactory bulb, pallium, basal
      telencephalon, ventral thalamus, tectum, and nucleus interpeduncularis.
      Comparison of these results with those obtained in other vertebrates, including a
      segmental approach to correlate cell populations, reveals that the cholinergic
      systems in amphibians share many features with amniotes. Thus, cholinergic
      pedunculopontine and laterodorsal tegmental nuclei could be identified in the
      amphibian brain. The finding of weakly immunoreactive cells in the striatum of
      Rana, which is in contrast with the condition found in Xenopus, Pleurodeles, and
      other anamniotes studied so far, has revived the notion that basal ganglia
      organization is more preserved during evolution than previously thought.

PMID- 9184997
TI  - Differential reinnervation of retinal bipolar cell dendrites and axon terminals
      by dopamine interplexiform cells following dopamine depletion with 6-OHDA.
AB  - Depletion of retinal dopamine in goldfish increases light sensitivity at photopic
      backgrounds. As horizontal cells appear not to be involved with this effect
      (Yazulla and Studholme [1995] Vis. Neurosci. 12:827-837), we investigated the
      innervation patterns of the ON rod/cone bipolar cells (ON-BC) by dopaminergic
      interplexiform cells (DA-IPCs) normally and during the period of neogeneration of
      new DA-IPCs at the marginal zone following DA-IPC destruction. DA-IPCs were
      destroyed via intraocular injection of 6-hydroxydopamine over 2 successive days.
      Controls and 1 year post-injection retinas were double labeled for protein kinase
      C and tyrosine hydroxylase (TH) immunocytochemistry to identify the ON-BCs and
      the DA-IPCs, respectively. Double-labeled 25 microns tissue sections were
      examined on a confocal laser scanning microscope by using dual channel
      immunofluorescence acquisition. Image stacks were analyzed for DA-IPC/ON-BC
      contacts in the distal inner nuclear layer (INL) and inner plexiform layer (IPL).
      Image stacks were rotated 180 degrees with respect to each other and reanalyzed
      to determine potential randomness of the contacts. For control retinas there were
      1.8 contacts/axon terminal in the IPL (n = 165) and 9.4 contacts/ON-BC in the
      distal INL (n = 28). At 1 year after injection, reinnervation of TH
      immunoreactive boutons in the retina recovered to 16% of control in the IPL but
      only 10% in the distal INL. Establishment of DA-IPC/ON-BC contacts recovered to
      36% of control for ON-BC axon terminals (n = 103), whereas there was no recovery
      of contacts in the distal INL (n = 30). Reinnervation of ON-BC by DA-IPCs
      preferentially targets the axon terminals. The absence of reinnervation of
      bipolar cell dendrites by DA-IPCs may account for the persistence of the
      increased light sensitivity following retinal dopamine depletion. Thus, dopamine
      input to ON-BCs in the outer retina maybe involved in setting background
      sensitivity under photopic conditions.

PMID- 9184998
TI  - Endovascular treatment of abdominal aortic aneurysms: lessons learned.
AB  - The authors offer an overview of their 20-year involvement in the development of
      an endovascular graft for abdominal aortic aneurysm exclusion. Clinical
      experience gained throughout 6 years of clinical evaluation are reviewed, along
      with observations and insights on preoperative assessment, implantation
      techniques, and complications.

PMID- 9184999
TI  - Imaging modalities for aortic endografting.
AB  - One of the most fundamental and influential differences between conventional
      surgery and endovascular grafting for aortic aneurysm is the central role of
      imaging in every aspect of management. This review summarizes five imaging
      techniques for aortic endografting: intravascular ultrasound, contrast
      angiography, conventional computed tomography (CT), spiral CT with image
      processing, and magnetic resonance angiography (MRA). External ultrasound and
      intravascular ultrasound have important relevance to endovascular aortic surgery.
      Artifacts of arteriography include magnification, thrombus effect, fore
      shortening of tortuosity, loss of luminal detail, parallax error, and projection
      errors. Conventional CT scans have artifacts and difficulties also. Diameter
      measurement by CT suffers from methodology errors and observer variability. If
      conventional CT and angiography are used for endovascular aortic graft planning,
      both should be obtained since neither alone provides sufficient data. The use of
      spiral CT scanning and computerized image processing has clearly aided the
      preoperative definition of aneurysm morphology both in terms of dimensional
      accuracy and by adding diagnostic information. MRA is capable of producing three
      dimensional images, axial sections, and longitudinal projections in any plane. It
      can detect blood flow without contrast medium, but gadolinium enhances MRA by
      avoiding the "signal dropout" artifact. Technology exists to provide new forms of
      imaging for endovascular surgery that combines three-dimensional models with on
      line image data in a process called "data fusion." This may offer improved ease
      and accuracy for conducting endovascular procedures in the future.

PMID- 9185000
TI  - Three-year experience with the White-Yu Endovascular GAD Graft for transluminal
      repair of aortic and iliac aneurysms.
AB  - PURPOSE: To report a > 3-year experience with a modular, balloon-expandable
      endovascular graft used for aneurysm exclusion in the aorta and other arteries.
      METHODS: The customized White-Yu Endovascular GAD Graft, a woven polyester
      prosthesis with an intrinsic Elgiloy wire graft attachment system along the body
      of the graft, is a flexible endograft design available in straight, tapered, and
      bifurcated versions that can be delivered transluminally through 18F to 24F
      sheaths. RESULTS: Since July 1993, 93 patients have received the White-Yu
      endograft for treatment of 76 abdominal aortic, 3 thoracic aortic, 13 iliac, and
      1 popliteal aneurysms. Of the 79 aortic procedures, 39 involved straight tube
      grafts, 20 were tapered aortoiliac models, and 20 were bifurcated devices.
      Success rates for tube grafts were 81% in the abdominal aorta and 100% for the
      thoracic aorta; 5 primary endoleaks (14%) and 2 conversions to surgery (5.6%)
      occurred with this graft type. Aortoiliac grafts were deployed successfully in
      95% (19/20) of cases with 1 conversion (5%) due to thrombosis. Seventy-five
      percent of the bifurcated endograft procedures were successful, with 4
      conversions (20%) for technical failures and 1 graft thrombosis. Four additional
      endografts were deployed to treat two primary and two secondary endoleaks in tube
      graft patients. Two access-related arterial injuries were treated surgically.
      There was one case of embolus to the distal femoral artery but no
      microembolization. Overall perioperative (30-day) mortality was 3.1%. Over a mean
      18-month follow-up (range 2 to 39), no late graft thrombosis, stenosis, or graft
      migration has been seen on CT scans or X ray. Endoleak has not been detected in
      any aortoiliac or bifurcated graft. Aneurysm size has diminished consistently in
      successfully treated cases. CONCLUSIONS: The White-Yu endograft appears to offer
      a safe, efficacious, and minimally invasive means of excluding aneurysms from the
      circulation. Improvements in patient selection, surgical techniques, and
      equipment have reduced the incidence of endoleak and conversion to open repair
      over the course of the evaluation.

PMID- 9185001
TI  - Two-center German experience with aortic endografting.
AB  - PURPOSE: To report the results of a two-center study of endovascular abdominal
      aortic aneurysm (AAA) exclusion using a polyester-covered nitinol stent-graft.
      METHODS: Candidates were evaluated with arteriography and computed tomography.
      Criteria for endovascular therapy were a proximal aortic neck > 10 mm in length
      and < 25 mm in diameter, no bilateral internal iliac artery involvement in the
      aneurysm, no markedly tortuous common iliac arteries (CIAs) or CIAs < 7 mm in
      diameter, and no superior mesenteric artery occlusive disease. Patients were
      treated with the Mialhe Stentor and Vanguard stent-grafts in either tube or
      bifurcated versions. RESULTS: Between August 1994 and November 1996, 149 patients
      (mean age 67 years, range 49 to 90) were admitted to the study. Overall primary
      technical success (aneurysm exclusion without endoleak) was 87% (130 patients):
      78% (7 patients) for tube grafts and 88% (123 patients) for bifurcated
      endografts. The rate of local, remote, or systemic complications was 10.8%, with
      a 30-day mortality rate of 0.7%. During an average 13.5-month follow-up, there
      were no late deaths. Four of 20 endoleaks sealed spontaneously, 14 were treated
      with endoluminal techniques, and 2 remain untreated by patient request. Three
      graft limb thromboses occurred; one was treated surgically, one with lytic
      therapy, and one was untreated. Secondary patency was 96%. CONCLUSIONS:
      Endoluminal repair of infrarenal AAAs using straight or bifurcated grafts is a
      feasible alternative to conventional surgical repair. Longer follow-up and more
      experience with refined endograft models will elucidate the durability of this
      endovascular approach to treating AAAs.

PMID- 9185002
TI  - Endoluminal repair of abdominal aortic aneurysms: strengths and weaknesses of
      various prostheses observed in a 4.5-year experience.
AB  - PURPOSE: To summarize the results of endovascular abdominal aortic aneurysm (AAA)
      treatment using several endograft designs over a 4.5-year experience and offer
      comparisons on the various devices. METHODS: From May 1992 to August 1996, 121
      AAA patients meeting the criteria for an endoluminal repair were treated with 1
      of 5 endograft designs in three configurations. The endografts were implanted in
      the operating room under fluoroscopic control. Follow-up included contrast
      enhanced computed tomography within 10 days of operation, 6 months
      postoperatively, and annually thereafter. RESULTS: Endografts were successfully
      deployed in 106 patients (88%). Fifteen cases were converted to open repair. Six
      procedure-related deaths occurred within 30 days owing to myocardial infarction
      (3), combined renal failure and septicemia (2), and multisystem failure (1).
      There were 36 local/vascular complications (30%) and 18 systemic/remote
      complications (15%). Of the 121 patients undergoing endoluminal AAA repair, 93
      (77%) are currently alive and well with their AAAs excluded from the circulation.
      CONCLUSIONS: Trends in endoluminal AAA repair and prosthetic design point toward
      simpler devices and earlier treatment of smaller aneurysms once the long-term
      outcome of aortic endografting has been determined.

PMID- 9185003
TI  - Endoleak as a complication of endoluminal grafting of abdominal aortic aneurysms:
      classification, incidence, diagnosis, and management.
AB  - The inability to obtain or maintain a secure seal between a vessel wall and a
      transluminally implanted intra-aneurysmal graft is a complication unique to the
      evolving technique of endovascular aneurysm exclusion. Because the term "leak"
      has long been associated with aneurysm rupture, the term "endoleak" is proposed
      as a more definitive description of this phenomenon. Embracing both persistent
      blood flow into the aneurysmal sac from within or around the graft (graft
      related) and from patent collateral arteries (nongraft related), endoleak can be
      classified as primary or secondary depending on the time of occurrence (within 30
      days of implantation or following apparent initial seal, respectively).
      Diagnostic techniques to detect endoleak include arteriography, intraprocedural
      pressure monitoring, contrast-enhanced computed tomography, abdominal X ray, and
      duplex scanning. Management strategies for endoleak range from observation with
      periodic imaging surveillance to correction by additional endoluminal or surgical
      procedures. Standardization of the terminology describing this important sequela
      to endovascular aneurysm exclusion should facilitate uniform reporting of
      clinical trial data vital to the evaluation of this emerging technique.

PMID- 9185004
TI  - Biological responses to endovascular treatment of abdominal aortic aneurysms.
AB  - PURPOSE: To review the findings of two studies investigating the apparent
      differences in inflammatory responses demonstrated in patients undergoing
      endovascular as opposed to classic surgical treatment of abdominal aortic
      aneurysms (AAAs). METHODS: The clinical course of seven patients treated with an
      endoluminal procedure (AAA-E) and seven patients undergoing conventional surgery
      (AAA-C) were compared (all men; ages 52 to 80 years). Blood samples were taken
      pre-, intra-, and postoperatively for up to 7 days. Inflammatory responses were
      assessed from measurement of interleukins (IL)-1 beta, IL-6, IL-8, and tumor
      necrosis factor (TNF-alpha); complement proteins C1q, C4, C5a, and terminal
      complement complexes, C5b-C9; and C-reactive proteins. Granulocyte and monocyte
      surface adhesion molecule expression was determined indirectly using a panel of
      monoclonal antibodies against CD11a, CD11b, CD11c, CD18, and L-selectin in donor
      white blood cells exposed to patient plasma. RESULTS: In six of the AAA-E
      patients, blood pressure decreases were recorded during the introduction of the
      device. Elevated body temperature was sustained for 2 to 5 days postoperatively
      in the AAA-E group. IL-6 levels were significantly higher in AAA-C patients (p <
      0.0005), while TNF-alpha release was recorded in the AAA-E group only. CD11b,
      CD11c, and CD18 molecules on both granulocytes and monocytes were significantly
      upregulated 60 minutes after the endovascular procedure compared to conventional
      surgery. CONCLUSIONS: Endovascular aortic aneurysm repair apparently induces a
      significant inflammatory response, mainly involving TNF-alpha release, which
      differs from open AAA repair. These inflammatory responses, which may be related
      to the observed intraprocedural blood pressure decreases, could be caused by cell
      activation arising from intra-aneurysmal device manipulation.

PMID- 9185005
TI  - Aortomonoiliac endovascular grafting: difficult solutions to difficult aneurysms.
AB  - PURPOSE: To describe a refined technique for aortomonoiliac endograft exclusion
      of abdominal aortic aneurysms (AAAs). METHODS: A tapered aortomonoiliac graft was
      prepared from an 8-mm thin-walled expanded polytetrafluoroethylene tube graft
      predilated proximally to 35 mm and tapered distally to 15 mm. The proximal graft
      was sutured to a 5-cm-long, predilated Palmaz stent, which was mounted on a 30-mm
      balloon and backloaded into a 21F packaging sheath. With the patient under
      general anesthesia and both common femoral arteries exposed, the endograft was
      anchored in the infrarenal aorta and subsequently passed into one iliac system,
      where it was anastomosed to the iliac or femoral vessels. The contralateral
      common iliac artery was occluded, and an extra-anatomic, femorofemoral, or
      iliofemoral bypass grafting was performed. RESULTS: Twenty of the 25 AAAs treated
      to date with this technique have been successful, with aneurysm exclusion
      achieved in 18 (2 minor distal endoleaks are scheduled for endovascular repair).
      The technical failures were analyzed, resulting in enhancements to the technique.
      Complications included 2 early (< 30 days) deaths, 1 case of minor embolization,
      1 transient renal failure, 1 pulmonary embolus, and 1 wound infection. The only
      late complication was a graft infection localized to the groin. CONCLUSIONS:
      Aortomonoiliac endovascular aneurysm repair is effective in patients with AAAs
      involving the iliac arteries. Short-term results are acceptable, but long-term
      efficacy must be addressed before this procedure is widely adopted. Technical
      changes made in response to early learning curve problems have led to a safer,
      more reliable procedure.

PMID- 9185006
TI  - The EVT tube and bifurcated endograft systems: technical considerations and
      clinical summary. EVI Investigators.
AB  - Endovascular exclusion of abdominal aortic aneurysms (AAAs) is an investigational
      technique under scrutiny around the world. The tube and bifurcated versions of
      the Endovascular Grafting System (EGS) developed by Endovascular Technologies are
      the subjects of FDA-approved multicenter trials in the United States (US).
      Similar studies are under way in Europe, Australia, and the United Kingdom. This
      review details the implantation techniques for the EGS device and summarizes the
      important clinical findings published through 1996. Although the EGS was
      voluntarily removed from the US trial when fractures were discovered in the graft
      attachment system, subsequent experience with the re-engineered EGS has been
      positive. Successfully implanted EGS tube grafts have been associated with
      aneurysm shrinkage after 1 year in AAAs initially excluded or with sealed
      endoleaks. Aneurysm enlargement has been seen in EGS tube grafts with persistent
      endoleak.

PMID- 9185007
TI  - What are the characteristics of the ideal endovascular graft for abdominal aortic
      aneurysm exclusion?
AB  - PURPOSE: To review the anatomic factors crucial to successful endoluminal
      abdominal aortic aneurysm (AAA) repair and propose an ideal endograft design for
      AAA exclusion. METHODS AND RESULTS: The anatomic features of critical importance
      to endovascular AAA exclusion comprise remote arterial access, proximal and
      distal fixation sites, AAA morphology, and arterial wall pathology. When
      designing an aortic endograft, the major components to consider are stent
      selection, graft material, and the delivery system. The ideal endograft design
      must be sufficiently versatile to treat a broad range of patients. To meet this
      requirement, the endograft should display a high degree of dimensional
      adaptability. A modular bifurcated endograft design permits intraoperative
      customization to tailor the device to each patient's anatomy and pathology.
      CONCLUSIONS: The modular stent-graft concept addresses many of the important
      factors in the evolution toward an ideal aortic endograft. Extensive testing will
      be needed to determine if the bifurcated stent-graft described here is the
      optimal design for effective AAA exclusion.

PMID- 9185008
TI  - Evaluation of endovascular abdominal aortic aneurysm repair: anatomical
      classification, procedural success, clinical assessment, and data collection.
AB  - PURPOSE: To detail a methodology for evaluation of endovascular abdominal aortic
      aneurysm (AAA) repair that has been achieved through consensus of an
      international multidisciplinary team of investigators. METHODS: This schema
      features an anatomical classification for AAAs, a definition of procedural
      success, and a procedure for clinical assessment, as well as the necessary data
      collection forms. Patient data include demographics, procedural and clinical
      success, complications, and follow-up. Procedural details can be related to
      anatomic situations, comorbid processes, devices, and effective aneurysmal
      exclusion. RESULTS: These data would allow assessment of the procedures,
      physician learning curves, procedural indications, techniques, methodologies, the
      relationship of indications to success and complications, devices and subsequent
      graft patency, and aneurysmal exclusion. CONCLUSIONS: The use of this
      standardized data collection system could enable physicians and industry to
      better understand endovascular AAA repair and ultimately improve patient care.

PMID- 9185009
TI  - Uptake and decay of volatile organic compounds at environmental concentrations:
      application of a four-compartment model to a chamber study of five human
      subjects.
AB  - Five subjects were exposed to nine volatile organic compounds (VOCs) at
      concentrations that can be encountered in everyday life. Breath samples were
      collected during a 10-h uptake phase and a 24-h decay phase. It was possible to
      determine four distinct slopes in the decay curve for each chemical. The
      distribution in the body and residence times in different tissues were calculated
      using a linear four-compartment mass-balance model. The model was used to predict
      breath concentrations for two subjects in a second chamber experiment including
      the same nine VOCs, representing three chemical classes (aromatic, aliphatic, and
      chlorinated compounds). Predicted values were generally within 25% of those
      observed, suggesting that the model parameters calculated here could be useful in
      estimating exposure and body burden to other VOCs in these three classes. Median
      residence times for the nine VOCs ranged from 3-12 min for compartment 1
      (metabolizing); 0.3-2 h for compartment 2; 2-5 h for compartment 3; and 1-4 d for
      compartment 4. The fraction of the parent compound exhaled at equilibrium was
      estimated to range from 0.06-0.16 for four aromatic compounds and decane; 0.22
      0.23 for trichloroethylene and dichloromethane; 0.35 for hexane; and 0.88 for
      1,1,1-trichloroethane. Limited blood measurements were obtained for six of the
      nine VOCs in two subjects simultaneously with the breath samples over four-hour
      decay periods. Blood/breath ratios agreed well between the two subjects, but were
      higher than human blood/air partition coefficients reported in subjects exposed
      to high concentrations. This observation is consistent with results from other
      studies at relatively low concentrations.

PMID- 9185010
TI  - Measurement of background urban nitrogen dioxide pollution levels with passive
      samplers in Montpellier, France.
AB  - Background nitrogen dioxide (NO2) pollution levels in Montpellier were measured
      in the context of an assessment operation carried out by the local monitoring
      network (AMPADI-LR), using Palmes passive samplers. The equipment was validated
      by continuous measurement with automatic chemiluminescence analyzers.
      Measurements from representative background pollution sites and the ensuing
      cartographic representation provide information about local pollution data, a
      description of seasonal evolution and an assessment of the influence of various
      sources. The study may be used to define parameters for establishing an exposure
      index, taking into account roads with heavy traffic, which affects the
      distribution of NO2 over Montpellier, and meteorological factors. This is a pilot
      study which will subsequently be used for a more precise assessment measuring the
      personal exposure of inhabitants, for the purposes of a study on effects on
      health.

PMID- 9185011
TI  - Systemic uptake of chromium in human volunteers following dermal contact with
      hexavalent chromium (22 mg/L).
AB  - This study examined the systemic uptake of chromium in four human volunteers
      following three hours of contact with water containing hexavalent chromium
      [Cr(VI)] at a concentration of 22 mg/L. Volunteers were immersed below the
      shoulders in water at 91 +/- 2.5 degrees F. On the day prior to the experiment
      and for five days afterwards, samples of urine, plasma, and red blood cells
      (RBCs) were collected and analyzed for total chromium. Red blood cell chromium
      concentrations were used as a specific biomarker for systemic uptake of Cr(VI).
      Although total chromium concentrations in RBCs and plasma increased relative to
      historical background concentrations on the day of exposure, no sustained
      elevation of chromium concentrations was observed in RBCs or plasma of the
      volunteers tested. Since absorption of chromium in the hexavalent state would
      result in the irreversible binding of Cr(VI) to hemoglobin within the RBC
      (manifested as a sustained elevation of total chromium concentrations in the
      RBC), the pattern of blood uptake and urinary excretion observed was consistent
      with uptake and distribution of chromium in the trivalent state. Small increases
      were observed in the concentration of total chromium in urine within 48 h of
      exposure, indicating that some trivalent chromium [Cr(III)] may have penetrated
      the skin at a rate of about 3.3 x 10(-5) to 4.1 x 10(-4) micrograms/ cm2-h. In
      short, the data indicated that a 3-h contact with Cr(VI) at concentrations in
      water plausible for environmental exposure (e.g., swimming) was not expected to
      result in systemic uptake of measurable amounts of Cr(VI), although a small
      quantity of Cr(VI) may have penetrated the skin where it was subsequently reduced
      to Cr(III) prior to systemic uptake.

PMID- 9185012
TI  - Comparative evaluation of methods for estimating potential human exposure to
      ozone: photochemical modeling and ambient monitoring.
AB  - Photochemical modeling and ambient monitoring of ground-level ozone
      concentrations provide two alternative/complementary methods for calculating
      potential population exposure estimates. A comparative evaluation of these
      methods was undertaken over a study area comprised of the entire state of New
      Jersey and neighboring parts of Delaware, Maryland, Pennsylvania, and New York.
      Kriging, a geostatistical interpolation technique, was used for the interpolation
      of hourly ozone data from 38 air quality monitoring stations operating within the
      study area, to derive concentration fields for the entire domain. The Urban
      Airshed Model (UAM-IV), a comprehensive photochemical grid-based model, was then
      used to calculate the same concentrations from emissions and meteorology inputs.
      Concentration fields, thus developed, were linked with corresponding population
      data to calculate potential population exposure estimates to outdoor ozone
      (Ep.o). The adequacy of kriging as an interpolation technique was evaluated by
      comparing Ep.o estimates derived via photochemical UAM modeling with those
      calculated by using concentrations obtained from kriging UAM-calculated values at
      the locations of the monitoring stations. In general, UAM was found to predict
      higher Ep.o compared to those derived by kriging observations. In order to test
      the robustness of the interpolation methodology with respect to assumptions of
      statistical correlation, two different semivariogram models, spherical and
      exponential, were used for kriging. Application of the different semivariograms
      yielded almost identical Ep.o patterns.

PMID- 9185013
TI  - Pesticide exposures to children from California's Central Valley: results of a
      pilot study.
AB  - In response to concerns about pesticide use and evidence that contaminants may
      accumulate in house dust, the California Department of Health Services (DHS)
      conducted a pilot study of pesticide contamination in rural children's home
      environments. House dust samples for pesticide analysis were collected from
      eleven homes, five of which had at least one farmworker (FW) resident. Handwipe
      samples were collected from one child at each residence (ages 1-3 years). Ten of
      33 pesticides tested in house dust were detected. Excluding non-detects,
      concentrations for diazinon ranged from 0.7-169 ppm in four FW homes and 0.2-2.5
      ppm in three non-farmworker (NFW) homes (overall median = 1 ppm), suggesting a
      difference between FW and NFW homes. Chlorpyrifos ranged from 0.2-33 ppm in three
      FW homes and < 1 ppm in two NFW homes (overall median < 0.5 ppm). All other
      pesticides were detected at < 2 ppm at four or fewer homes. The sources of these
      compounds could not be determined. Co-located samples were considerably different
      in concentration and loading, indicating intra-household variation. Of nine
      compounds tested, diazinon and chlorpyrifos were found on the hands of two or
      three FW children (20-220 ng/hand). Dust ingestion scenarios show child exposures
      could exceed the United States Environmental Protection Agency Office of
      Pesticide Program diazinon chronic reference dose (9 x 10(5) mg/kg/day). The
      results suggested that pesticide residues are present in the home environment of
      some California children and are likely to contribute to exposures. Additional
      research is feasible and needed to assess the magnitude and distribution of these
      risks.

PMID- 9185014
TI  - Hair nicotine concentrations in mothers and children in relation to parental
      smoking.
AB  - The health effects of environmental tobacco smoke (ETS) exposure constitute a
      main public health problem. Lack of presice methods for assessing personal
      tobacco smoke exposure, makes it difficult to estimate the health effects of such
      exposure. Measuring hair nicotine concentrations could be an improvement in the
      assessment of personal tobacco smoke exposure. The objective of the present study
      was to estimate quantitatively the relation between hair nicotine concentrations
      in mothers and children and tobacco smoke exposure assessed by questionnaires.
      Mothers' and children's hair nicotine concentrations in the proximal 2 cm of hair
      were measured in 94 families with children 12-36 months of age: 25 nonsmoking
      families, 40 families with one smoking parent, and 29 families with both parents
      smoking. Questionnaire information on tobacco smoke exposure was collected from
      the same families. In multivariate linear regression analysis, children's
      nicotine levels were linearly related to daily number of cigarettes smoked at
      home by both mothers (0.8 mg/g increase per cigarette, 95% confidence interval
      [CI] 0.43-1.18), and fathers (1.3, 0.81-1.73). Mothers' nicotine levels were
      linearly related to both personal smoking (2.7, 1.75-3.55) and fathers' smoking
      at home (2.1,0.74-3.49). Hair nicotine seems to be a good quantitative measure of
      exposure to tobacco smoke during the previous months both among active and
      passive smokers. The non-invasive and simple collection procedure makes the
      method especially suitable for estimating tobacco smoke exposure in children.

PMID- 9185015
TI  - Modeling magnetic fields in residences: validation of the resicalc program.
AB  - RESICALC is a computer program that models magnetic fields due to currents on
      arbitrary arrays and configurations of electric transmission lines, primary and
      secondary distribution lines, and ground and neutral return pathways. The program
      conducts network analyses of ground/neutral currents in neighborhoods based on
      residential loads and impedances in the current path. Experiments were conducted
      at the Magnetic Field Research Facility (MFRF) in Lenox, Massachusetts to
      validate the program's field computation. MFRF has a simulated residential
      electric distribution system that permits the testing of scenarios with a broad
      range of electrical characteristics. The results demonstrate that the program
      accurately models fields from complex combinations of supply and ground/neutral
      currents, and shows how estimated fields may be sensitive to impedance values
      assigned to the ground and neutral currents. The program has usefulness as an
      exposure assessment tool when access to residences is not possible, and as a
      means to estimate fields when planning electrical facility or residential
      development. Careful mapping of power line and residential coordinates in the
      program, as well as acquiring the highest quality load and grounding data
      available, are critical for modeling valid exposure estimates.

PMID- 9185016
TI  - New federalism and intergovernmental fiscal relationships: the implications for
      health policy.
AB  - This paper explores a number of popular but largely inaccurate myths about
      American federalism in order to clarify the fundamental structures and processes
      that characterize American federal governance. Examination of financial and
      political trends over the past several decades reveals the development of a form
      of functional specialization among national, state, and local governments based
      on pragmatic responses to policy problems rather than decisions based on clearly
      articulated "principles." These responses have increasingly come from states in a
      wide variety of policy areas, including health care, where the energetic reform
      activity of the past decade provides a sharp contrast to the inability of the
      national government to enact reform. Recent pressure to devolve more authority to
      the states is thus much more than an ideological fad; it reflects widespread
      agreement among political elites that state and local governments have become
      capable governing partners. Nonetheless, there are limits to devolution which
      guarantee that close fiscal and political ties between the nation and the states
      will remain in place. Devolution does not, because it cannot, mean separation.

PMID- 9185017
TI  - Translating ideas into actions: entrepreneurial leadership in state health care
      reforms.
AB  - States are often touted as "laboratories" for developing national solutions to
      social problems. In this article we examine the appropriateness of this metaphor
      for comprehensive health care reform and attempt to draw lessons about policy
      innovation from recent state actions. We present evidence from six states that
      enacted major pieces of health care legislation in the late 1980s or early 1990s:
      Massachusetts, Oregon, Florida, Minnesota, Vermont, and Washington State. The
      variation in design casts doubt on the proposition that states can invent plans
      and programs for other states and the federal government to adopt for themselves.
      Instead, we argue that it is more accurate to think of states as specialized
      political markets in which individuals and groups develop and promote innovative
      products. We examine the factors that might create receptive markets for
      comprehensive health care reforms and conclude that the critical factor these
      states shared in common was skilled and committed leadership from "policy
      entrepreneurs" who formulated the plans for system reform and prominent
      "investors" who contributed substantial political capital to the development of
      the reforms. We illustrate different strategies that leaders in these states used
      to carry out the entrepreneurial tasks of identifying a market opportunity,
      designing an innovation, attracting political investment, marketing the
      innovation, and monitoring its early production.

PMID- 9185018
TI  - Laboratories and the health care marketplace: the limits of state workforce
      policy.
AB  - Nearly every state has enacted its own effort to change both the composition and
      the practice patterns of America's medical workforce. At the same time, the
      health care marketplace is altering the nation's medical workforce, encouraging
      more medical students to enter primary care and fewer to become specialists. In
      this article, I consider various issues raised by these trends. Do the various
      state programs constitute an effective policy laboratory? Is the market solving
      problems government could not? Are the government initiatives now irrelevant? I
      conclude that the market is solving the problem of specialty maldistribution (too
      many specialists) but not the problem of geographic maldistribution (too many
      medically underserved communities). I also conclude that state workforce efforts
      have not constituted good policy laboratories and that only federal action can
      seriously address the geographic maldistribution problem.

PMID- 9185019
TI  - The Medicaid managed care policy consensus for welfare recipients: a reflection
      of traditional welfare concerns.
AB  - An Aid to Families with Dependent Children (AFDC)-Medicaid managed care policy
      consensus has emerged in the American states. Although there are two main
      organizational forms--primary care case management and risk-based capitation
      models--states are converging on the risk-based approach for their AFDC
      recipients. Risk-based Medicaid managed care for AFDC recipients assumes a
      distinct purpose and meaning. The reform is not just about cost control and
      improving access but about enduring welfare concerns: deservingness, need, and
      empowerment. Despite recent federal policies that have essentially severed the
      eligibility link between AFDC and Medicaid, state policy elites still conceive of
      poor families on Medicaid as a "welfare" group. Assumptions about the need for
      behavior modification and the need to integrate this group into "mainstream"
      America shape perceptions about why Medicaid managed care is appropriate for AFDC
      Medicaid recipients.

PMID- 9185020
TI  - Medicaid and the politics of groups: recipients, providers, and policy making.
AB  - There is a substantial heterogeneity of interests within the Medicaid program.
      Its major beneficiary groups include the elderly, people with disabilities,
      children in low-income families, and adults receiving Aid to Families with
      Dependent Children. Providers who deliver medical services to these recipients
      represent another set of potential claimants. These groups are likely to be
      treated differently by the politics that affect the design and management of the
      Medicaid program. The Medicaid recipient groups vary in several important
      dimensions: First, the groups differ politically, a dimension that includes their
      political participation, their relationships to parties and electoral coalitions,
      the images they present to other political actors, and the legacy of public
      policies that affect them. Second, the groups have different medical and social
      needs. Third, the groups differ with respect to economic constraints, including
      the political economy of labor markets and of government spending programs, and
      they have differing relationships to the various types of medical providers. The
      medical providers are themselves political actors with a variety of
      characteristics that create political advantages relative to recipients, although
      there is also diversity among providers. The politics of the Medicaid program
      involves more than simply technical decisions about eligibility, coverage of
      medical services, reimbursement, and the implementation of managed care
      initiatives. Instead the differences between the program's multiple claimants are
      an important element of current Medicaid politics and the likely path of future
      reforms.

PMID- 9185021
TI  - Politics matters! Health care policy and the federal system.

PMID- 9185022
TI  - State health policy analysis: on the abuse of metaphor and the pathology of
      variation.

PMID- 9185023
TI  - Commentary: calcium antagonist controversy, does the accusing finger also point
      to beta-blockers and methyldopa?

PMID- 9185024
TI  - Calcium channel blockers and cardiac mortality in the treatment of hypertension:
      a report from the Department of Health Hypertension Care Computing Project
      (DHCCP).
AB  - OBJECTIVE: A case control study has reported a 60% higher risk of myocardial
      infarction in hypertensives treated with a calcium channel blocker (CCB). We
      examined the Department of Health Hypertension Care Computing Project (DHCCP)
      data to see if we could confirm or refute this suggestion. DESIGN: Two case
      control studies, matched and unmatched, plus two longitudinal studies from 1 year
      of presentation, one for all subjects given a CCB for more than 1 year compared
      with those not given this drug, and the second comparing survival on the
      different drugs initially given between 3 and 12 months of follow-up. SUBJECTS: A
      total of 9328 subjects were included in the analyses and 2154 died. Of these,
      6406 received one or more of the following index drugs: 26% a calcium channel
      blocker (CCB); 84% a diuretic; 29% alpha methyldopa; 12% a beta-blocker (BB); and
      11% an angiotensin-converting enzyme (ACE) inhibitor. The CCBs were nifedipine,
      diltiazem or verapamil. RESULTS: In the case control studies a group given
      diuretics +/- other treatments (but not including one of the index drugs)
      provided a reference group with a relative risk (RR) of 1.0. In the matched case
      control study the adjusted RR for a CCB without a diuretic was 1.32 (95% CI 0.64
      2.70) for IHD mortality and 1.05 (95% CI 0.60-1.84) for cardiovascular mortality.
      Similar results were observed for methyldopa, BBs and ACE inhibitors. The results
      in the unmatched case control analysis were also similar. The longitudinal study
      comparing all those treated for over 1 year with a CCB with all other treatments
      showed a RR for total mortality of 1.03 (95% CI 0.85-1.25). The longitudinal
      study of total mortality according to treatment initiated at 3-12 months found
      results of a similar magnitude for CCBs, methyldopa and BBs. CONCLUSIONS: The
      reference diuretic group had less severe cardiovascular disease than other
      groups. Treatment with a CCB, BB or methyldopa was associated with an excess
      mortality in comparison with this reference group. The excess was similar in the
      different drug groups.

PMID- 9185025
TI  - Hypertension awareness, treatment and control in the community: is the 'rule of
      halves' still valid?
AB  - One of the cornerstones of the primary prevention of cardiovascular disease has
      been screening and early antihypertensive drug treatment of patients with high
      blood pressure (BP). Nevertheless, recent population studies have shown that
      awareness and management of high BP levels are far from optimal. In this study,
      we performed a search for publications providing frequencies of hypertension
      awareness, treatment and control in different populations. In men, the
      frequencies of awareness, antihypertensive drug treatment and BP control among
      all hypertensive patients varied between 23% and 93%, 5% and 89% and 5% and 87%,
      respectively. In women, the frequencies ranged between 28% and 97%, 6% and 97%,
      and 0% and 97%, respectively. The percentage of aware hypertensives who were
      under antihypertensive drug treatment varied between 47% and 95% in men and
      between 50% and 100% in women. The percentage of hypertensives who were under
      antihypertensive drug treatment varied between 47% and 95% in men and between 50%
      and 100% in women. The percentage of treated hypertensives achieving an adequate
      BP control varied between 29% and 95% in men and between 0% and 100% in women.
      Overall, women had a better awareness, treatment and control status for
      hypertension than men, and worse in developing countries than in industrialised
      countries. Hypertension awareness, treatment and control improved with time,
      together with the proportion of diagnosed hypertensive patients under treatment
      and the proportion of well controlled among treated hypertensive patients. We
      conclude that although the 'rule of halves' no longer applies for screening and
      treatment of hypertension in industrialised countries, it might still be valid
      for developing countries and for the effectiveness of antihypertensive drug
      treatment in all countries.

PMID- 9185026
TI  - Patients' perceptions of changes in their blood pressure.
AB  - OBJECTIVES: (1) To investigate patients' experience of changes in their blood
      pressure (BP) in an every day setting and the accuracy of patients' predictions;
      and (2) to examine what influences patients' belief that they can tell when their
      BP is up. SUBJECTS: A total of 102 hypertensive patients were recruited
      sequentially as they presented for routine BP checks. The setting was an inner
      city general practice. DESIGN: Patients attended for BP checks on a weekly basis.
      Before each check they were asked whether they thought their BP was higher, lower
      or the same as usual. Subjects were classified as predictors if they thought they
      could tell when their BP was up. On completing their series of BP checks each
      subject completed symptom and Hospital Anxiety and Depression questionnaires.
      MAIN OUTCOME MEASURES: Accuracy of BP predictions, BP levels and variability,
      number of symptoms reported and anxiety level. RESULTS: One hundred and two
      hypertensive patients entered the study of whom 51 patients were predictors. The
      majority (86%) of predictors could not accurately predict their BP. There were no
      significant differences in either BP or variability between predictors and non
      predictors. Predictors were significantly more anxious and reported more symptoms
      than non-predictors. CONCLUSIONS: For the majority of predictors there is no
      significant relationship between predictions of BP and clinical measurements.
      Predictor status is associated with the reporting of more symptoms and higher
      levels of anxiety. Doctors should counsel patients against using subjective BP
      assessments to guide their use of antihypertensive medication.

PMID- 9185027
TI  - Variation of ambulatory blood pressure in healthy middle-aged men.
AB  - The majority of the reference data on ambulatory blood pressure (ABP) monitoring
      is based on fixed, predefined times for waking hours and sleep. Our aim was to
      determine the level of ABP according to diary entries when awake, at work, at
      home and during sleep in a sample of normotensive, middle-aged men. The dipping
      status was also determined. All measurements were taken with a non-invasive
      auscultatory device on a normal working day. A total of 62 clinically healthy,
      normotensive men without a history of elevated BP were included. The mean resting
      BP of the group was 122/73 mm Hg. The 24-h systolic BP (SBP) was 114.4 +/- 8.6 mm
      Hg (95% CI 112.3, 116.6), while the diastolic BP (DBP) was 80.4 +/- 7.2 mm Hg
      (95% CI 78.5, 82.2). SBP when awake was 120.5 +/- 9.4 mm Hg (95% CI 118.1, 122.9)
      and diastolic pressure 84.4 +/- 7.7 mm Hg (95% CI 82.5, 86.4). The corresponding
      values for systolic and diastolic pressures during sleep were 101.2 +/- 8.5 mm Hg
      (95% CI 99.1, 103.4) and 71.7 +/- 7.7 mm Hg (95% CI 69.7, 73.6). The difference
      between day and night was 19.2 +/- 7.0 mm Hg for systolic and 12.7 +/- 6.0 mm Hg
      for diastolic pressure. The number of men whose systolic and diastolic pressure
      dropped less than 10% while asleep (non-dippers) was eight (13%) and 15 (24%),
      respectively. If the mean +/- 2 standard deviation interval is considered, the
      range of normality averaged 102-139/69-100 mm Hg when awake, 84-118/56-87 mm Hg
      when asleep and 97-132/66-95 over 24 h. The awake-sleep pressure difference did
      not correlate with the 24-h average.

PMID- 9185028
TI  - Genetic and environmental factors regulating blood pressure in childhood:
      prospective study from 0 to 3 years.
AB  - OBJECTIVES: Blood pressure (BP) regulation depends on the interaction between
      multiple environmental and genetic factors. Of these, BP sensitivity to dietary
      sodium intake has been one that has been investigated in adults but not in
      children. The aim of the present study was to investigate, prospectively, the BP
      profile in relation to different genetic and hormonal factors, in the first 3
      years of life. POPULATION AND METHODS: Thirty-nine children born at term
      following normal pregnancies, with uncomplicated neonatal periods, were randomly
      selected to take part in the study. BP, weight and length were evaluated every 3
      months from birth to 3 years. At the age of 12 months, haptoglobin phenotypes and
      plasma active renin concentration were determined as well as random urine
      evaluation of aldosterone, cAMP, dopamine and digoxin-like immunoreactive
      substances (DLIS). Family history of cardio-vascular diseases was also recorded.
      RESULTS: Systolic BP (SBP) demonstrated a gradual increase until the age of 6
      months with little variation up to 36 months. Tracking of SBP values was also
      observed from the first year as infants with high values (above the 75
      percentile) maintained this tendency up to, at least, the age of 36 months. The
      comparison between SBP and diastolic BP (DBP) according haptoglobin phenotypes
      demonstrated that SBP was systematically higher in allele 1, with apparently an
      increasing tendency with age, although the differences did not have statistical
      significance. The comparative study between haptoglobin phenotypes, with
      correction for the covariates fractional excretion of sodium and potassium,
      showed that allele 1 carriers had significantly lower plasma renin and urine
      aldosterone and cAMP concentrations than allele 2, but dopamine excretion was
      found to be higher in allele 1 than in allele 2. There were no differences among
      variables relating to family history of cardiovascular disease. CONCLUSIONS:
      There was an early tracking process of BP values from the first 6 months of life
      which persists through, at least, to the age of 36 months. Differences in sodium
      handling between haptoglobin 1 and 2 phenotypes were already present in early
      childhood, although no significant repercussion in BP values could be
      demonstrated in the 3-year duration of this study.

PMID- 9185029
TI  - Evaluation of indapamide 1.25 mg once daily in elderly patients with mild to
      moderate hypertension.
AB  - The objective of this study was to evaluate the safety and efficacy of indapamide
      1.25 mg once daily as monotherapy in elderly patients (65 years and older) with
      mild to moderate essential hypertension. Two hundred and seventy-nine (279)
      elderly patients were enrolled in a washout period, during which patients
      received single-blind placebo for 4 weeks. Patients demonstrating supine
      diastolic pressures between 95 mm Hg and 114 mm Hg at the end of the 4-week
      placebo washout period were entered into the 8-week double-blind treatment
      period. Two hundred and four (204) patients qualified for the study and were
      randomized to the double-blind treatment; 103 patients received indapamide 1.25
      mg and 101 patients received placebo for 8 weeks. Overall, 177 patients (92
      indapamide and 85 placebo) completed the study. The primary efficacy criterion
      was the mean change in supine diastolic blood pressure (DBP) from double-blind
      baseline to the end of 8 weeks of therapy. By week 8 of the double-blind
      treatment period, indapamide 1.25 mg produced a statistically significant (P =
      0.0037) decrease in supine DBP of 8.2 mm Hg compared to a decrease of 5.3 mm Hg
      produced in the placebo group. Additionally, indapamide 1.25 mg was statistically
      (P = 0.0028) more effective than placebo in reducing supine systolic BP (SBP) (
      10.1 vs -4.2 mm Hg). The incidence of drug-related adverse events during the
      double-blind treatment period was similar between the two treatment groups. A low
      dose of indapamide, 1.25 mg, given once daily for 8 weeks was effective as
      monotherapy with respect to BP reduction in an elderly population with mild to
      moderate hypertension. Indapamide 1.25 mg was safe and generally well tolerated
      in this elderly patient population.

PMID- 9185030
TI  - World Hypertension League statement. Hypertension control in the world: an agenda
      for the coming decade. Based on the 1995 WHL Ottawa Declaration.

PMID- 9185031
TI  - Lack of effect of a diuretic added to diltiazem.

PMID- 9185032
TI  - Angiotensin-I converting enzyme (ACE) gene polymorphism and the erythrocyte
      sodium-lithium countertransport in hypertension.

PMID- 9185033
TI  - High affinity binding sites for 12(R)-Hydroxyeicosatrienoic acid [12(R)-HETrE] in
      microvessel endothelial cells.
AB  - 12(R)-HETrE is an NADPH-dependent arachidonic acid-derived metabolite whose
      synthesis is induced several fold in inflamed corneal epithelium correlating with
      the development of the in situ inflammatory response, i.e., vasodilation, PMN
      chemotaxis, endothelial cell mitogenesis, and neovascularization. Because this
      novel eicosanoid may serve as an endogenous mediator of the angiogenic response
      in the cornea during inflammation we probed microvessel endothelial cells for a
      specific binding site which could possibly account for the mechanism by which
      this eicosanoid initiates changes in cellular activity. Binding of radioactive
      ligand [3H-12(R)-HETrE] was saturable with time and concentration. Scatchard
      analysis indicated a single, saturable binding site for 12(R)-HETrE with a Bmax =
      24,700 sites/cell and an apparent Kd = 0.043 nM. Thin layer chromatography
      analysis of cell-associated ligand revealed that esterification of 12(R)-HETrE
      was 2-7 fold less than unesterified, cell bound ligand. The concentrations of
      12(R)-HETrE at which maximum biological activity has been observed, i.e., 0.1 nM,
      roughly corresponds to the Kd value, suggesting a functional link to this binding
      site. These studies begin to reveal a potential mechanism by which 12(R)-HETrE
      stimulates microvessel endothelial cells to invade the cornea leading to corneal
      neovascularization.

PMID- 9185035
TI  - The Guinea Pig Blinking Test: a comparison with human responses.
AB  - The Guinea Pig Blinking Test (2) was presented as a model for the selection and
      development of comfortable ocular formulations. This study compares human
      nociceptive responses and the blinking response of the guinea pig to different
      concentrations of a topically applied ophthalmic drug, sulfacetamide. The number
      of human subjects noting pain upon instillation of various concentrations of
      sulfacetamide (3) was compared to the blinking responses of guinea pigs treated
      with 2.5%-17.5% sulfacetamide. The number of blinks was counted over a period of
      5 minutes following (1) saline (0.9% NaCl), and (2) 30-60 minutes later a test
      solution. A Blinking Index (B.I.) = blinks drug/blinks saline was calculated for
      each animal. The dose/response curves of both humans and guinea pigs were almost
      identical, showing a threshold at 5% sulfacetamide, followed by a linear
      increase, reaching a maximum at 12.5%-15% sulfacetamide. A 2.5% solution that
      elicited pain in 10% of human subjects yielded a B.I. = 1.04 +/- 0.05, whereas a
      12.5% solution that elicited pain in 95% of human subjects yielded a B.I. = 1.61
      +/- 0.13 (mean +/- S.E., n = 10, P < 0.05). The strong linear relationship
      between the guinea pig blinking response and the human perception of pain,
      following identical treatment with a topical ophthalmic drug, demonstrates that
      this animal test can be useful in predicting the degree of ocular discomfort of
      human subjects.

PMID- 9185034
TI  - Microplate assay of ascorbic acid in aqueous humor with bicinchoninic acid.
AB  - An inexpensive microplate assay method was developed to determine ascorbic acid
      in human aqueous humor samples. The method is based on the selective oxidation of
      ascorbic acid at alkaline pH and determination of ascorbic acid and other
      reducing substances in samples with bicinchoninic acid/CuSO4 before and after the
      alkaline treatment. The two-point measurement eliminates the effect of
      interfering substances, such as glucose, uric acid and glutathione, which are
      stable at alkaline pH. The advantages of the method are that it requires small
      sample volumes and allows handling of a large number of samples simultaneously.

PMID- 9185036
TI  - The choroidal blood flow response after flicker stimulation in chicks.
AB  - Form-deprivation myopia (FDM) can be prevented by exposing the animal to
      stroboscopic illumination (10 Hz). Flicker illumination is known to stimulate the
      release of dopamine (DA) from the retina. We hypothesize that DA was released and
      diffused into the choroid. To prove this hypothesis, we decided to undertake an
      investigation in chicks and measure choroidal blood flow (ChBF) during
      stimulation of the ocular fundus with diffuse flicker. White Leghorn chicks (2
      weeks old) were used for this study. Different flash stimulations (5 Hz
      approximately 50 Hz) were given for 3 minutes, then ChBF was recorded with the
      PeriFlux flowmeter simultaneously and continuously for 5 minutes. Some birds are
      recorded up to 120 minutes to find out any late-onset effect. The ChBF was
      increased after flicker stimulation. The difference was statistically significant
      in 10 Hz, 20 Hz, and 30 Hz. The ChBF can maintain 20% higher for 60 minutes.
      Therefore, flicker illumination preventing FDM may be induced by the
      hyperactivity of ganglion cells, then stimulates the release of DA from the
      retina and suppresses the development of myopia.

PMID- 9185037
TI  - Anterior chamber angles shallowing and intraocular pressure after topical
      pilocarpine.
AB  - Pilocarpine has been well recognized as the drug of choice for acute angle
      closure glaucoma. The purpose of this study is to clarify quantitatively the
      change of anterior chamber angle and depth with the passage of time after
      pilocarpine drop administration. Chamber angles of the four quadrants and chamber
      depths were measured in 18 normal subjects by Scheimpflug Video Image prior to
      and 30, 60, and 180 minutes after administration of one drop of 4% pilocarpine in
      one eye, while the opposite eye served as control. The anterior chamber angle and
      depth showed a significant shallowing at 30, 60 and 180 minutes after 4%
      pilocarpine administration with a maximal effect of -3.61 degrees and -0.15 mm at
      30 minutes, respectively, while the reduction of intraocular pressure reached its
      maximal effect at 180 minutes. These facts should be well understood in the
      treatment of angle-closure glaucoma.

PMID- 9185038
TI  - The effect of 0.5% timolol maleate on the ocular perfusion of ocular hypertensive
      patients by scanning laser flowmetry.
AB  - To understand the effect of 0.5% timolol maleate on the ocular perfusion of the
      optic disc and macula in ocular hypertensive patients, we enrolled 10 males and
      15 females without any systemic or ocular disease, except intraocular pressure
      higher than 20 mmHg. Their average age was 33 +/- 13 y/o (range 14-45). Under the
      randomized, double-masked design, one drop of 0.5% timolol maleate was given in
      one eye, and placebo in the fellow eye. Heart rate, blood pressure, intraocular
      pressure, and ocular perfusion were measured at baseline, and then 30 minutes and
      2 hours after treatment. Ocular perfusion was measured by Heidelberg Retina
      Flowmeter (Heidelberg Engineering GmbH, Heidelberg, Germany). We used 10 degrees
      measurement field and 10 x 10 pixels measurement frame. Four areas were measured,
      i.e., temporal upper, temporal lower, and nasal parts of the optic disc, and
      macula. In comparison to the baseline, the treated eyes had a slight reduction of
      blood flow, volume, and velocity 30 minutes after treatment, but these parameters
      came back close to the baseline value at 2 hours after treatment. Similar changes
      were also noted in the control eyes. The results showed that a single drop of
      0.5% timolol had minimal effects on the retinal and macular circulation within 2
      hours after treatment.

PMID- 9185039
TI  - Subconjunctival retention of C3F8 gas increased the success rates of
      trabeculectomy in young people.
AB  - In this study, the effect of subconjunctival retention of perfluoropropane (C3F8)
      gas on trabeculectomy was evaluated to determine if this maneuver would increase
      the success rate of the surgery. Thirty-two patients (under 35 years old) with a
      diagnosis of primary open-angle glaucoma or steroid-induced glaucoma were
      randomized into two groups to receive trabeculectomy: Group A (trabeculectomy
      alone, 16 eyes) and Group B (trabeculectomy with subconjunctival retention of 0.5
      mL pure C3F8 gas, 16 eyes). The results showed that the typical appearance of a
      subconjunctivally retained C3F8 filtering bleb is highly distended in the first
      two weeks after surgery, followed by flattening and diffusing gradually. The
      average retention time of C3F8 gas within the subconjunctival space is 28 +/- 6
      days. A higher success rate was noted in Group B than in Group A (94% versus 50%,
      p = 0.016) at a mean follow-up time of 12 months. However, there were no
      differences in complication rates and results of final visual acuity between the
      two groups (both groups had two patients lose more than two lines of vision, p =
      1.0). Our study suggests that subconjunctival retention of C3F8 gas increases the
      success rate of trabeculectomy in young people in the intermediate-term (12
      months) follow-up period.

PMID- 9185040
TI  - Assessment of muscarinic transmission in the superior cervical and ciliary
      ganglion of the cat.
AB  - This study was undertaken to determine if muscarinic mechanisms are involved in
      synaptic transmission in the parasympathetic ciliary ganglion as has been clearly
      shown for sympathetic ganglia. Cats were anesthetized, and following topical
      ephedrine, pupillary constrictions were elicited by electrical stimulation of the
      intracranial oculomotor nucleus. Nictitating membrane contractions were evoked by
      electrical stimulation of the preganglionic cervical nerve. Frequency-response
      curves were repeated after infusion with hexamethonium (0.6-1.0 mg/kg min-1) and
      after subsequent administration of atropine (500 micrograms/kg. i.v.). In other
      experiments, effects of nicotinic (DMPP) and muscarinic (McN-A-343) agonists on
      postganglionic ciliary nerve activity were measured. Treatment with hexamethonium
      reduced nictitating membrane responses at all frequencies of stimulation (by
      about 75% at 16-32 Hz). The residual nictitating membrane contractions were
      subsequently blocked by the addition of atropine. In contrast, hexamethonium
      totally abolished miosis produced by CNS preganglionic oculomotor nerve
      stimulation. The nicotinic agonist, DMPP, produced nictitating membrane
      contractions, miosis, and increased ciliary nerve firing. In contrast, McN-A-343
      contracted the nictitating membrane but failed to increase postganglionic ciliary
      nerve activity. These results suggest that, unlike sympathetic ganglia, a
      significant degree of muscarinic transmission does not occur in the
      parasympathetic ciliary ganglion.

PMID- 9185041
TI  - The regulation of the scleral growth associated with deprivation myopia in
      chicks.
AB  - The mechanism of axial elongation caused by experimental or clinical myopia is
      still unknown. We sought to explore the changes of scleral chondrocytes during
      myopia formation through the cell biology model. White Leghorn chicks were used
      for this study. The right eye was covered with a translucent goggle after
      hatching, and the left eye was left uncovered for control. The chicks were
      maintained on 12 hours light-dark cycle for two weeks, then sacrificed every
      other day and the eyeballs removed for study. Our results in the primary culture
      of scleral chondrocytes showed that the densities of chondrocytes on myopic eyes
      were significantly higher than those of the controlled non-myopic eyes, and 3H
      thymidine incorporation rate also increased with the increasing of the
      concentration of fetal bovine serum. The PCNA index of chondrocytes in myopic
      eyes was also higher than that of the controlled non-myopic eyes. Thus, axial
      elongation of experimental myopia in the chick is the result of active tissue
      remodeling rather than passive scleral stretching alone.

PMID- 9185042
TI  - Role of cyclic AMP in hydrogen peroxide-induced potentiation of sympathetic
      neurotransmission in the bovine iris.
AB  - Hydrogen peroxide (H2O2) has been shown to enhance electrically-evoked
      norepinephrine (NE) release from isolated, superfused bovine irides. Since
      stimulation of presynaptic adenylyl cyclase can potentiate sympathetic
      neurotransmission in several tissues, the present study considered the
      possibility that cyclic AMP may mediate the effects of H2O2 in the iris. Isolated
      bovine irides were prepared for analysis of field stimulation-induced [3H]NE
      release using the superfusion method. Both the diterpene activator of adenylyl
      cyclase, forskolin and the cyclic AMP-specific phosphodiesterase inhibitor, RO
      201724 enhanced evoked [3H]NE overflow by 32%. On the other hand, inhibition of
      cyclic AMP-dependent protein kinase I/II by Rp-cAMPS attenuated field-stimulated
      [3H]NE release by 20%. Interestingly, both RO-201724 and Rp-cAMPS did not alter
      the enhancement of electrically-evoked [3H]NE overflow caused by submaximal
      concentrations of H2O2. We conclude that cyclic AMP may be involved in the
      pathway leading to NE release from sympathetic nerves in the bovine isolated
      iris. However, cyclic AMP may not be a mediator of H2O2-induced potentiation of
      sympathetic neurotransmission in this tissue.

PMID- 9185043
TI  - Acetaminophen cytotoxicity in mouse eye: mitochondria in anterior tissues are the
      primary target.
AB  - Acetaminophen (APAP) injected into C57BL/6 mice (cytochrome P450 inducer
      responsive strain) that had been pretreated with b-naphthoflavone (BNF) produced
      ocular tissue damage, including cataract. Our previous histocytochemical studies
      showed that tissue damage spread in association with the flow of the aqueous
      humor and appeared first in the ciliary epithelium, followed by the iris and
      corneal endothelium and, finally, the lens. The neural retina, retinal pigmented
      epithelium and choroid remained unaffected. A close examination of the affected
      tissues indicated that mitochondria are the primary target of APAP cytotoxicity.
      In order to investigate whether the respiratory capacity of mitochondria is more
      sensitive to APAP cytotoxicity than mitochondrial morphology, we determined in
      this work the oxygen uptake by eye tissues dissected from BNF-pretreated and APAP
      injected C57BL/6 mice. Oxygen uptake by the ciliary body/iris decreased about 60%
      at 90 min and 85% at 120 min after APAP administration. The oxygen uptake was
      inhibited about 50% by 10 microM rotenone. Since the earliest sign of
      mitochondrial damage was noted at 120 min, the result indicates that
      mitochondrial energy dysfunction precedes morphological alterations. It was also
      observed that oxygen uptake by the retina remained unaffected at least for 120
      min after APAP administration; therefore, it is evident that the retina and,
      possibly, other posterior tissues as well are resistant to APAP cytotoxicity, not
      only in their morphology but, also, in their capacity of mitochondrial energy
      metabolism.

PMID- 9185044
TI  - PAF antagonists as possible inhibitors of corneal epithelial defects and
      ulceration.
AB  - The extracellular matrix (ECM) plays a crucial role in cell adhesion,
      differentiation and wound-healing. Its stability is tightly controlled by enzymes
      that regulate the metabolism of its components (e.g collagen, fibronectin,
      laminin). We have found that in the cornea, a potent lipid inflammatory mediator
      platelet-activating factor (PAF) activates the expression of two
      metalloproteinases (MMP-1 and MMP-9) as well as urokinase-plasminogen activator
      (uPA). uPA is of particular interest because, as a serine protease, it is at the
      top of the protease cascade. PAF may contribute to the destruction of the ECM and
      the formation of epithelial defects and corneal ulcers by activating uPA and then
      proteases. We also investigated how several PAF antagonists with different
      binding affinities can block the expression of the uPA gene. Our results suggest
      that PAF antagonists with affinities for intracellular binding sites and/or
      specific structures derived from triazolobenzodiazepine could be of therapeutic
      use to limit the breakdown of the ECM and the development of ulcer formation.

PMID- 9185045
TI  - Alternative method of conservative esthetic treatment for gingival recession.
AB  - The health and appearance of gingival tissue play an essential role in esthetics.
      The esthetic function of the tissue is enhanced when it frames the restoration.
      With gingival recession, the effect of natural gingiva is created with pink
      composites or ceramics on the cervical part of the crown, as described in this
      clinical report. This goal depends on the absence of adverse effects on the
      color, shape, and health of the surrounding tissue. The new composites are more
      color stable and wear resistant, and the latest generation of dental bonding
      agents allows the bonding of composites to dentin, various metals, and porcelain.
      The application of soft-tissue colored composite on dentin cementum, enamel, or
      porcelain is a good solution for correcting gingival recessions.

PMID- 9185046
TI  - A facial prosthesis made of porcelain fused to metal: a clinical report.

PMID- 9185047
TI  - Surface treatment of indirect resin composite surfaces before cementation.
AB  - STATEMENT OF PROBLEM: Controversy surrounds the use of hydrofluoric acid to
      prepare precementation surfaces of indirect composites. PURPOSE: This study was
      conducted to compare effects of combining hydrofluoric or orthophosphoric acid
      with microetching as precementation treatments. MATERIAL AND METHODS: Nine
      specimens of three composite materials were prepared to simulate heat-cured
      indirect restorations. The specimen surfaces were prepared with one of three
      treatments. Adhesive Bond II and Twinlook cements were used to bond a phosphoric
      acid-etched disk of P50 to the treated surface. Analysis of variance and Scheffe
      tests were used to assess the bond strength data. Scanning electron microscopy
      and microscopic analysis of the fractured and treated surfaces were also
      performed. RESULTS: Bond strengths for all surface treatments did not
      significantly differ. Hybrids had a higher bond strength with etching than
      microfills, and mechanical roughening produced the greatest bond strengths with
      microfills. Microetching with orthophosphoric acid produced higher bond strengths
      than microetching with hydrofluoric acid on hybrids. CONCLUSIONS: Acid etching
      alone is not sufficient to produce effective bond strengths, and hydrofluoric
      acid treatments are detrimental to the resin composite.

PMID- 9185048
TI  - The influence of surface loading and irradiation time during curing on mechanical
      properties of a composite.
AB  - PURPOSE: The aim of this study was to determine the influence of different
      surface loadings during curing with various irradiation times on hardness and
      diametral tensile strength of a light-cured composite. MATERIAL AND METHODS: A
      mold was fabricated to allow loading during curing of cylindrical specimens of a
      composite. Four surface loadings of 0, 0.35, 0.87, and 1.73 MPa and four
      irradiation times of 20, 40, 60, and 180 seconds were used (n = 15). Each
      specimen was subjected to a microhardness test and to a diametral tensile
      strength test. RESULTS: Surface loading during curing affected both hardness and
      strength properties, whereas irradiation time influenced only the hardness of the
      material. Both parameters gained between 15% and 20% improvement when the
      material was loaded with 0.87 MPa surface pressure and cured by 60-second
      irradiation time. Higher loading or longer irradiation times did not improve
      these properties. CONCLUSION: Loading composite during curing improves its
      mechanical properties, probably through decreasing flaws and air voids of the
      material.

PMID- 9185049
TI  - Enhanced permeability of acid-etched or ground dental enamel.
AB  - STATEMENT OF PROBLEM: Acid etching creates retentive microcraters on enamel
      surfaces. Designing of a partial denture often involves reshaping the supporting
      and retentive teeth by grinding the enamel. Unfortunately, both these procedures
      damage the enamel surface. In vivo such surface damage takes several months to
      recover. PURPOSE: This study evaluated the effect of 1-minute etching, prolonged
      etching, and grinding on the permeability of dental enamel for water-soluble
      molecules. MATERIAL AND METHODS: With the electron paramagnetic resonance and a
      two-chamber diffusion cell, the influence of etching and grinding on the
      diffusion of spin label molecules through the enamel was studied quantitatively.
      The enamel permeability was measured in 30 sound enamel samples, of which 10
      samples were exposed to 1-minute etching with 37% phosphoric acid, 10 samples
      were etched for 5 minutes, and 10 samples were ground with a diamond bur. RESULTS
      AND CONCLUSIONS: All procedures significantly increased the permeability of
      dental enamel. These results demonstrate that in vivo the acid-etched and ground
      dental enamel surfaces are less protected and consequently, unless the tooth is
      properly protected, are more susceptible to carious lesions. Therefore ground or
      accidentally etched enamel should be protected.

PMID- 9185050
TI  - A short-term clinical follow-up study of superplastic titanium alloy for major
      connectors of removable partial dentures.
AB  - STATEMENT OF PROBLEM: Superplastic forming of Ti-6A1-4V alloy has been used in
      the fabrication of a removable denture framework. The method provides the
      titanium alloy denture framework with excellent physical properties not seen in
      cast titanium prostheses. PURPOSE: This study describes the technical procedure
      for fabricating removable dentures with this type of framework and evaluates
      clinical applications of the dentures in short-term follow-up periods from 6
      months to 3 years. RESULTS: Results of this study demonstrated that the dentures
      functioned well and did not cause any major clinical difficulties. The patients
      have expressed satisfaction with the dentures at regular recall appointments.
      CONCLUSION: The clinical observations suggest that this method is suitable for
      fabricating titanium alloy removable dentures.

PMID- 9185051
TI  - Functional units, chewing, swallowing, and food avoidance among the elderly.
AB  - PURPOSE: The number of teeth in the dentition was compared with the number and
      types of dental functional units (opposing tooth pairs) to correlate the number
      of functional units with complaints about chewing and swallowing in the elderly.
      MATERIAL AND METHODS: Complaints of oral pharyngeal function and food avoidance
      practices were compared with the number and types of functional units. A
      convenience sample of 602 elderly subjects (468 men, 134 women, mean age 70
      years) were interviewed and examined dentally. RESULTS: Functional unit measures,
      which included functional arrangement of the teeth and the number and type of
      teeth present, were found to be more discriminatory and descriptive of
      masticatory potential than the more number of teeth. Elderly persons (> or = 60
      years of age) with reduced numbers of functional units tended to report
      difficulty chewing, avoidance of stringy foods (including meat), crunchy foods
      (including vegetables), and dry solid foods (including breads), and difficulty in
      swallowing. Removable prostheses did not appear to prevent these consequences
      and, at least in this elderly population, did not appear to be equivalent to
      natural teeth in terms of masticatory potential. CONCLUSIONS: It is possible that
      compromised dental function results in the swallowing of poorly chewed food, food
      avoidance patterns, dietary inadequacies, and systemic changes favoring illness,
      reduced vigor, debilitation, and shortened life expectancy. Emphasis should be
      placed on maintaining natural teeth whenever possible.

PMID- 9185052
TI  - Resorption of mandibular canal wall in the edentulous aged population.
AB  - STATEMENT OF PROBLEM: The mandibular canal wall may be affected by the progress
      of residual ridge resorption after tooth extraction. Little knowledge is
      available regarding the relationship of specific systemic factors and the
      resorption of the mandibular canal wall. PURPOSE: The purpose of this study was
      to assess the status of the mandibular canal in the edentulous mandible and to
      determine whether there is any relationship between the resorption of the
      mandibular canal wall and selected health indices in the elderly. MATERIAL AND
      METHODS: The status of the mandibular canal was assessed from panoramic
      radiographs of 128 edentulous elderly subjects (32 men and 96 women). RESULTS:
      The superior border of the mandibular canal was more frequently resorbed in women
      (32.6%) than in men (9.8%). Resorption in the mandibular canal wall was
      significantly more prevalent in subjects with asthma (odds ratio: 6.0), with
      thyroid disease (odds ratio: 3.04), and with a cortical thickness at the
      mandibular angle less than 1 mm thick (odds ratio 2.74). CONCLUSION: The findings
      suggest that gender, asthma, and thyroid disease play important roles in
      resorption of the mandibular canal wall.

PMID- 9185053
TI  - Effects of long-term storage on properties of an alginate impression material.
AB  - STATEMENT OF PROBLEM: Storage stability is a critical characteristic for
      perishable dental materials. PURPOSE: The purpose of this shelf-life study was to
      document changes in the properties of an alginate impression material on exposure
      to various environmental conditions for more than 78 months. MATERIAL AND
      METHODS: Properties measured included recovery from deformation, strain in
      compression, compressive strength, tear strength, working time, and creep
      compliance. RESULTS: Results revealed increases in strength and working time and
      a decrease in recovery from deformation at 30 to 50 months: strength and recovery
      then remained constant past 6 years, whereas working time and creep compliance
      decreased. Only the most stressful environmental conditions (heat and humidity)
      caused spontaneous failure of the material to set. CONCLUSIONS: We concluded
      that, under most storage conditions, properties of the alginate material tested
      remain within ADA specification limits well past manufacturer's designated shelf
      life. ADA specifications should require manufacturers to verify that the shelf
      life of each perishable material is based on valid data. An accelerated aging
      test was developed to simulate real time property changes and to assist in
      evaluating similar materials.

PMID- 9185054
TI  - Mechanical and elemental characterization of solder joints and welds using a gold
      palladium alloy.
AB  - PURPOSE: This study was conducted to determine whether newer infrared or laser
      welding technologies created joints superior to traditional furnace or torch
      soldering methods of joining metals. It was designed to assess the mechanical
      resistance, the characteristics of the fractured surfaces, and the elemental
      diffusion of joints obtained by four different techniques: (1) preceramic
      soldering with a propane-oxygen torch, (2) postceramic soldering with a porcelain
      furnace, (3) preceramic and (4) postceramic soldering with an infrared heat
      source, and (5) laser welding. MATERIAL AND METHODS: Mechanical resistance was
      determined by measuring the ultimate tensile strength of the joint and by
      determining their resistance to fatigue loading. Elemental diffusion to and from
      the joint was assessed with microprobe tracings. Scanning electron microscopy
      micrographs of the fractured surface were also obtained and evaluated. RESULTS:
      Under monotonic tensile stress, three groups emerged: The laser welds were the
      strongest, the preceramic joints ranged second, and the postceramic joints were
      the weakest. Under fatigue stress, the order was as follows: first, the
      preceramic joints, and second, a group that comprised both postceramic joints and
      the laser welds. Inspection of the fractographs revealed several fracture modes
      but no consistent pattern emerged. Microprobe analyses demonstrated minor
      diffusion processes in the preceramic joints, whereas significant diffusion was
      observed in the postceramic joints. CLINICAL IMPLICATIONS: The mechanical
      resistance data conflicted as to the strength that could be expected of laser
      welded joints. On the basis of fatigue resistance of the joints, neither infrared
      solder joints nor laser welds were stronger than torch or furnace soldered
      joints.

PMID- 9185055
TI  - Effects of adhesive primers on bond strength of self-curing resin to cobalt
      chromium alloy.
AB  - PURPOSE: This study evaluated the effects of four adhesive primers on the shear
      bond strength of a self curing resin to cobalt-chromium alloy. MATERIAL AND
      METHODS: The adhesive primers Acryl Bond (AB), Cesead Opaque Primer (COP), Metal
      Primer II (MPII), and MR Bond (MRB) were used. A brass ring placed over the
      casting alloy disk surface nonprimed or primed with each primer was filled with
      the self-curing methyl methacrylate polymethyl methacrylate resin. The specimens
      were stored in water at 37 degrees C for 24 hours and then alternately immersed
      in water baths at 4 degrees C and 60 degrees C for 1 minute each for up to 20,000
      thermal cycles before shear mode testing at a crosshead speed of 0.5 mm/min.
      RESULTS: All the primers examined improved the shear bond strength between the
      resin and cobalt chromium alloy compared with nonprimed specimens before thermal
      cycling. However, after 20,000 thermal cycles, the bond strengths of resin to
      cobalt chromium alloy primed with COP or MPII primers were significantly greater
      than those of specimens primed with AB or MRB primers and nonprimed controls.
      CONCLUSION: This study indicated that COP and MPII are effective primers to
      obtain higher bond strength between resin and cobalt-chromium alloy.

PMID- 9185056
TI  - Judson C. Hickey Scientific Writing Award Winner. Fabrication of a guide for
      nonradiographic evaluation of bone contour.
AB  - The determination of bony contours at the site of implant placement aids the
      surgeon and the restoring dentist in treatment planning a patient's care.
      Although radiographic evaluations that use cross-sectional views are helpful,
      they are often expensive and not available in most dentists' offices. This
      article describes a technique for the fabrication of a guide for nonradiographic
      evaluation of bone contour. Bone contours are probed and transferred to a
      sectioned cast by the use of a guide.

PMID- 9185057
TI  - Repair with a surveyed cast clasp while patient retains the partial denture.
AB  - A technique is described that allows a removable partial denture with a broken
      clasp or a removable partial denture in which an abutment has been extracted to
      be restored by the reattachment of a new cast clasp component or a complete
      surveyed clasp assembly. The technique is applicable to most clasp designs and
      can include attachment to the acrylic denture base or the metal major connector.
      The technique is distinguished from other repair techniques by (1) providing a
      cast clasp replacement, (2) allowing the patient to retain the prosthesis during
      the repair, (3) generating a precisely formed surveyed clasp assembly by the
      laboratory, and (4) including an efficient transfer mechanism for the precision
      clasp created in the laboratory to be attached to the removable partial denture
      in the dental office. A two-step impression procedure is used to ensure proper
      relation of the partial denture to the abutments.

PMID- 9185058
TI  - Palatal impression template for a fully edentulous arch during stage I implant
      placement.
AB  - It is often desirable to insert a fixed provisional resin restoration at stage II
      surgery when the implants are uncovered. It satisfies the patient's esthetics,
      phonetics, and functional demands and helps create a good emergence profile for
      the healing gingival tissue. This article presents a procedure that enables the
      clinician to fabricate a full-arch maxillary provisional restoration for a fully
      edentulous patient, which can be delivered at second-stage surgery at the time of
      uncovering the implants.

PMID- 9185059
TI  - Esthetic and functional incisal enameloplasty.

PMID- 9185060
TI  - Provisional fixed prosthesis reinforced with a metal casting.

PMID- 9185061
TI  - Retrofitting a dowel and core to an existing crown.

PMID- 9185062
TI  - The all-acrylic resin mandibular removable partial denture: design
      considerations.

PMID- 9185063
TI  - Maintaining proper framework/altered master cast relationship when processing the
      distal extension removable partial denture: a simple technique.

PMID- 9185064
TI  - An annotated bibliography of Latin American psychotherapy studies.
AB  - This article reviews the literature produced by Latin American investigators on
      the efficacy of psychotherapy. Sixteen studies are described in relation to the
      aims of the study, patients' diagnoses, sample size, theoretical framework,
      intervention time, data collection, and main results. Few studies of this type
      were found, and they were mainly open trials with methodological limitations.
      Comparison of results was difficult because authors did not plan studies with a
      view to their being compared. The state of psychotherapy in Latin America is
      discussed.

PMID- 9185065
TI  - The psychosocial treatments interview for anxiety disorders. A method for
      assessing psychotherapeutic procedures in anxiety disorders.
AB  - The authors report on development, reliability, and findings of the Psychosocial
      Treatments Interview (PTI) to assess treatments reported by patients in a
      naturalistic study of the longitudinal course of anxiety disorders. The PTI
      ascertains frequency of different types of psychosocial treatments, based on
      patients' reports. The PTI showed good internal consistency and very good
      interrater reliability. At first 6-month follow-up, the most common modalities
      were supportive, medication discussion, and dynamic intervention. Combinations
      were common. Delivery of treatments differed by site. Overall, the PTI fills a
      methodological need for the assessment of the treatments reported by patients in
      naturalistic follow-up studies.

PMID- 9185067
TI  - Virtual reality exposure therapy.
AB  - It has been proposed that virtual reality (VR) exposure may be an alternative to
      standard in vivo exposure. Virtual reality integrates real-time computer
      graphics, body tracking devices, visual displays, and other sensory input devices
      to immerse a participant in a computer-generated virtual environment. Virtual
      reality exposure is potentially an efficient and cost-effective treatment of
      anxiety disorders. VR exposure therapy reduced the fear of heights in the first
      controlled study of virtual reality in treatment of a psychiatric disorder. A
      case study supported the efficacy of VR exposure therapy for the fear of flying.
      The potential for virtual reality exposure treatment for these and other
      disorders is explored, and therapeutic issues surrounding the delivery of VR
      exposure are discussed.

PMID- 9185066
TI  - Effectiveness of a training program for enhancing therapists' understanding of
      the supportive-expressive treatment model for breast cancer groups.
AB  - This study evaluated a training program for leaders of supportive-expressive
      psychotherapy groups for breast cancer patients. Twenty-four mental
      health/medical cancer care professionals completed two training phases and were
      tested for their understanding of the treatment model. Participants'
      understanding was enhanced as a result of the training program. This study
      demonstrates that a brief training program can improve therapists' understanding
      of the treatment model and demonstrates an effective method of evaluation. Future
      research should examine how performance on these tests generalizes to performance
      when leading a supportive-expressive group.

PMID- 9185068
TI  - Telepsychotherapy. Psychotherapy by telephone, videotelephone, and computer
      videoconferencing.
AB  - Telepsychotherapy is defined as psychotherapy conducted by a therapist at a
      location different from the patient's through bidirectional communication
      technology supporting real-time interactivity in the audio, audiovisual, or text
      modalities. Various types of telecommunication equipment are considered.
      Vignettes of 2 cases treated by means of the AT&T Videophone 2500 are presented.
      Medicolegal aspects and clinical issues, including ethics, confidentiality,
      patient selection, and therapy technique, are addressed.

PMID- 9185069
TI  - Resistance to medication during psychoanalysis.

PMID- 9185070
TI  - Psychiatrists treating physicians. Countertransference of a resident treating a
      depressed physician.

PMID- 9185071
TI  - Why prepare psychiatric residents for managed care?

PMID- 9185072
TI  - Identification of bioneutralization epitopes of human follicle stimulating
      hormone in the regions 31-52 and 66-75 of its beta-subunit.
AB  - The crucial role played by follicle stimulating hormone (FSH) in regulating both
      male and female reproduction and the possibilities of developing contraceptive
      methods for males by blocking the function of the hormone, makes it important to
      delineate the hormone-specific bioneutralization epitopes of human follicle
      stimulating hormone (hFSH) on its beta-subunit. Predictive methods were used to
      identify the potential surface-oriented regions of hFSH-beta. Peptides
      corresponding to these regions, i.e. 31-52, 66-75 and 86-95 hFSH-beta, were
      synthesized, anti-peptide antibodies were elicited in rabbits and the properties
      of these antisera to bind hFSH and neutralize its biological activity were
      assessed. Anti-31-52 hFSH-beta antisera bound hFSH specifically, whereas anti-66
      75 and anti-86-95 hFSH-beta antisera did not show any detectable binding, proving
      the region 31-52 hFSH-beta to be a specific antigenic determinant of hFSH. The
      bioneutralizing abilities of the anti-peptide antibodies were assessed by
      measuring the hFSH-induced progesterone secretion by rat granulosa cells in
      vitro. Antibodies to 31-52 and 66-75 hFSH-beta neutralized the bioactivity of
      hFSH, but anti-86-95 hFSH-beta antibodies did not. Furthermore, the three linear
      peptides and two disulphide looped peptides of 31-52 hFSH-beta and 86-95 hFSH
      beta were also subjected to the in-vitro granulosa cell assay. The linear
      peptides 31-52 hFSH-beta and 66-75 hFSH-beta and the cyclic 31-52 hFSH-beta
      disulphide loop peptide significantly inhibited the hFSH-induced progesterone
      secretion by rat granulosa cells, but the linear 86-95 hFSH-beta peptide and the
      corresponding cyclic disulphide loop peptide did not. The results clearly show
      that the regions 31-52 and 66-75 of hFSH-beta harbor bioneutralization epitopes
      of the hormone. The studies also indicate that cyclization of the linear 31-52
      hFSH-beta peptide greatly enhances receptor recognition and that the region 66-75
      hFSH-beta may also be involved in hormone-receptor interaction.

PMID- 9185074
TI  - Meeting on NK cell biology, Clamart, France, 1996.

PMID- 9185073
TI  - Phagocytosis by fresh and cultured human decidual stromal cells: opposite effects
      of interleukin-1 alpha and progesterone.
AB  - Flow cytometry and transmission electron microscopy have been employed to show
      that a proportion of fresh and cultured human decidual stromal cells phagocytose
      latex particles. Phagocytosis of Escherichia coli by cultured decidual stromal
      cells was, however, very low. Stimulation of cultured decidual stromal cells with
      interleukin-1 alpha enhanced phagocytosis of both latex particles and E. coli. In
      contrast, when decidual stromal cells were cultured with progesterone under
      decidualizing conditions, phagocytic activity was reduced. These results suggest
      the existence of an immune-endocrine circuit involving decidual stromal cells.

PMID- 9185075
TI  - PCR identification of class I major histocompatibility complex genes transcribed
      in mouse blastocyst and placenta.
AB  - We used an RT-PCR based strategy to amplify, clone and sequence MHC class I genes
      transcribed in the blastocyst and placenta of BALB/c mice. The PCR primers used
      were capable of amplifying many novel class I sequences from genomic DNA. By
      comparing the resulting sequence data with known class I sequences, we identified
      a number of different class I genes transcribed in these tissues. These include
      H2-K, -D, -L and a novel sequence in blastocysts, and H2-K, -D, -L, -D2, -T9, 
      T13, -T17, -T18, -M2 and three additional novel sequences in placenta. We
      postulate that some members of this spectrum of blastocyst and placentally
      expressed MHC class Ib genes may act together at the maternal-fetal interface in
      ways that are important for a successful pregnancy.

PMID- 9185076
TI  - Maternal serum granulocyte-colony stimulating factor in preterm birth with
      subclinical chorioamnionitis.
AB  - Preterm birth has been linked with intrauterine infection and inflammation. Serum
      and amniotic fluid markers of inflammation, such as interleukin-1 (IL-1), IL-6,
      and granulocyte-colony stimulating factor (G-CSF), have been associated with
      clinical chorioamnionitis and preterm delivery. As G-CSF regulates the production
      and maturation of neutrophils, we sought to determine if maternal serum G-CSF
      levels are elevated in patients with preterm birth with subclinical histologic
      chorioamnionitis. Maternal serum G-CSF levels were significantly different among
      five groups of women studied (P < .001, Kruskall-Wallis test), and were highest
      in subjects with preterm labor who delivered preterm (P < .05, Mann-Whitney U
      test). Among women with preterm labor who delivered preterm, maternal serum G-CSF
      levels were significantly higher if histologic chorioamnionitis was present than
      when histologic evidence of infection was not present (P = 0.04, Mann-Whitney U
      test). Intrauterine infection may cause a local inflammatory process and initiate
      preterm labor. This inflammatory response may include production of G-CSF, which
      would enter the circulation and stimulate the migration of neutrophils to the
      site of infection. Our data support this concept, as maternal serum G-CSF is
      elevated with subclinical infection in association with preterm birth.

PMID- 9185077
TI  - Tumor necrosis factor-beta in human pregnancy and labor.
AB  - The aims of this study were to determine tumor necrosis factor-beta (TNF-beta)
      concentration profiles in peripheral venous plasma and amniotic fluid during
      pregnancy and at the time of labor and to characterise TNF-beta mRNA expression
      and TNF-beta release from human gestational tissues. In addition, we investigated
      the expression of TNF-beta binding protein, lymphotoxin-beta (LT-beta), in human
      gestational tissues. The mean (+/-S.E.M.) TNF-beta concentrations in maternal
      plasma (TIL, 78 +/- 12 pg/ml, n = 7 vs. TNIL, 304 +/- 88 pg/ml, n = 7) and
      amniotic fluid (TIL, 8 +/- 5 pg/ml, n = 6 vs. TNIL, 73 +/- 20 pg/ml, n = 20) were
      significantly (P < 0.05) decreased in association with term labor-onset (TIL)
      compared to term not-in-labor (TNIL). TNF-beta concentration in maternal plasma
      and amniotic fluid did not change significantly either with preterm labor (PIL),
      or during pregnancy. Group-matched comparison of maternal plasma and amniotic
      fluid TNF-beta concentrations demonstrated that amniotic fluid TNF-beta
      concentrations were 6-8 fold lower than maternal plasma TNF-beta concentrations.
      Furthermore, no detectable TNF-beta was secreted from cultured human amniotic,
      choriodecidual and placental explants. Although, TNF-beta mRNA was detected in
      amnion, choriodecidual and placenta, LT-beta was similarly expressed in these
      tissues, suggesting that TNF-beta may be cell membrane bound. These data
      demonstrate that TNF-beta is present at low levels within the intrauterine
      environment and may suggest that TNF-beta is specifically inhibited at the
      maternal-fetal interface.

PMID- 9185078
TI  - Prevalence of elevated anticardiolipin antibodies in pregnant women with
      unexplained elevations of alpha-fetoprotein.
AB  - The goal was to determine what proportion of pregnant women with unexplained
      elevations of maternal serum alpha-fetoprotein (MSAFP) have increased levels of
      anticardiolipin antibodies (ACA), and if this might explain the increased
      prevalence of adverse pregnancy outcomes. Maternal serum alpha-fetoprotein levels
      of 12,295 pregnant women were evaluated at 15-19.5 gestational weeks. Elevated
      readings (> 2.5 MOM) were identified in 190 women (1.5%) and 86 (0.7%) of these
      had unexplained causes. Specimens (80) were recovered and ACA levels for
      cardiolipin were determined using enzyme-linked immunosorbant assay. Positive IgG
      ACA were identified in 10 out of 80 cases (12.5%) of elevated MSAFP; 3 out of 80
      cases (3.8%) had positive IgM ACA. The control women with normal MSAFP levels had
      positive IgG ACA in 3 of 86 cases (3.5%) and 1 of 86 cases (1.2%) for IgM. Women
      with increased MSAFP and positive ACA had infants with an average birth weight of
      2684 +/- 889 g compared to 2793 +/- 847 g in women with increased MSAFP and
      normal ACA. No significant differences in IgG ACA were found in pregnant women
      with unexplained elevated MSAFP (10/80, 12.5%) compared to women with normal
      MSAFP (3/86, 3.5%). As expected, lower birth weight was identified in women who
      had elevated MSAFP (2738 +/- 868 g) vs. women with normal MSAFP 3181 +/- 1082 g
      (P = 0.004), independent of ACA positivity.

PMID- 9185079
TI  - Possible association of infertility with sperm-specific abnormality of CD46.
AB  - Three infertile patients fulfilling normal or subnormal criteria on routine semen
      analysis showed abnormal sperm CD46 (membrane cofactor protein of complement) by
      SDS-PAGE/immunoblotting analysis using a panel of monoclonal antibodies. The
      sperm CD46 isoform has been reported to be associated with sperm-egg interaction.
      These three patients expressed normal CD46 isoforms on their lymphocytes and
      granulocytes. Sperm-specific abnormalities in these proteins thus parallel male
      infertility, suggesting a new category of infertility, probably due to
      aberrations in the molecules related to sperm-egg interaction.

PMID- 9185081
TI  - The effect of experimental fascioliasis on the pharmacokinetics of antipyrine and
      sulphadimidine in desert sheep.
AB  - Healthy adult male desert sheep were experimentally infected with Fasciola
      gigantica, to investigate the influence of experimental fasciolasis on the
      pharmacokinetics of antipyrine and sulphadimidine. Each animal received 500
      metacercariae orally. The experimental infection was confirmed histologically, by
      detection of Fasciola eggs in faeces and by measuring the activities of the
      enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate
      aminotransferase (AST) in plasma during the course of the disease. Changes in the
      pharmacokinetics of antipyrine and sulphadimidine were reported in the
      experimentally infected animals. Significant prolongation of antipyrine half life
      was observed 16 weeks after infection. The half-life of sulphadimidine was also
      significantly prolonged 5, 9 and 16 weeks after infection. Clearance of the
      sulphonamide was decreased significantly 5 and 9 weeks after infection and it
      regained its pre-infection value 16 weeks after infection.

PMID- 9185082
TI  - Concentrations of isometamidium chloride (Samorin) in sera of Zebu cattle which
      showed evidence of hepatotoxicity following frequent trypanocidal treatments.
AB  - The concentrations of isometamidium circulating in poorly nourished Zebu cattle
      which showed morbidity, mortality, and biochemical and histopathological evidence
      of hepatotoxicity, following frequent treatments with isometamidium chloride and
      diminazene aceturate were investigated using the isometamidium-ELISA. As few as
      two isometamidium treatments one month apart were associated with significant
      weight loss, and cattle treated with diminazene aceturate after three or four
      isometamidium treatments suffered a 50% mortality. Although there were no
      obvious, marked elevations in isometamidium concentration which might have
      allowed the use of the ELISA as a predictor of a potential toxicity problem,
      concentrations did increase significantly with the number of monthly treatments
      administered, suggesting drug accumulation, and the increases were significantly
      higher in cattle to which diminazene had also been administered. In cattle
      treated with both trypanocides, weight loss and serum glutamate dehydrogenase
      levels were correlated with isometamidium concentrations. These observations,
      together with the histopathological findings, support the hypothesis that the
      morbidity and mortality observed were related to the repeated treatment with
      isometamidium in conjunction with diminazene aceturate, and that the pathogenesis
      involved a component of hepatic damage. It is therefore recommended that cattle,
      particularly those under nutritional stress, are not subjected to repeated
      treatments with isometamidium at intervals as short as one month, and
      particularly not with concurrent administration of diminazene.

PMID- 9185083
TI  - Fluconazole in cats: pharmacokinetics following intravenous and oral
      administration and penetration into cerebrospinal fluid, aqueous humour and
      pulmonary epithelial lining fluid.
AB  - The pharmacokinetics of fluconazole following intravenous (i.v.) and oral (p.o.)
      administration and the penetration of fluconazole into cerebrospinal fluid,
      aqueous humour and epithelial lining fluid (ELF) of the lungs were evaluated in
      adult male cats. Pharmacokinetic parameters were calculated from serum
      concentration-time data obtained following i.v. and p.o. administration of 50 mg
      per cat using a cross-over study design. Fluconazole concentrations were measured
      using a high-performance liquid chromatography assay. Mean total body clearance
      of fluconazole was 37.7 mL/h.kg, mean volume of distribution at steady state was
      1.14 L/kg, mean residence time was 31.0 h and mean half-life of elimination was
      25 h as derived by non-compartmental analysis of data. Absorption was complete.
      Mean ratios of fluid:serum fluconazole concentrations following administration of
      50 mg fluconazole per day for 8 days were as follows: cerebrospinal fluid, 0.88;
      aqueous humour 0.79; ELF, 1.20. Fluconazole concentrations in cerebrospinal
      fluid, aqueous humour and ELF exceeded reported minimum inhibitory concentrations
      of fluconazole for pathogenic fungi. Results of this study suggest fluconazole
      can effectively be administered to cats at 50 mg per cat per day.

PMID- 9185084
TI  - Histamine mediates the muscle layer-specific responses in the isolated swine
      myometrium.
AB  - To clarify the role of histamine in uterine contractility, the effect of this
      biogenic amine on the myometrium of cyclic mature gilts was investigated by an
      isometric tension recording study in vitro. In addition, using crude membrane
      preparations isolated from the longitudinal (LM) and circular muscle (CM), the
      distribution of H1 histamine receptors was characterized by 3H-pyrilamine binding
      assay. Histamine caused a tetrodotoxin-resistant contractile response of LM and
      CM in Krebs solution, but LM (-logEC50 = 6.34) was more sensitive than CM (
      logEC50 = 5.4). Pyrilamine decreased the excitatory response of histamine in both
      muscle layers. In pyrilamine-treated LM, a high concentration of histamine (1-30
      microM) caused a slight inhibition of spontaneous contraction, and this
      inhibition was abolished by ranitidine. On the other hand, histamine did not
      cause any inhibition in the pyrilamine-treated CM preparations. Dimaprit (10-300
      microM) concentration-dependently inhibited the spontaneous contraction of LM but
      not of CM. In the presence of pyrilamine and ranitidine, N alpha-methylhistamine,
      even at 10 microM, did not affect the spontaneous and electrical field
      stimulation (5Hz)-induced contraction of LM and CM layers. Specific 3H-pyrilamine
      binding sites were distributed heterogeneously in the swine myometrium. The
      maximum number of binding sites in LM (132.5 +/- 9.9 fmol/mg protein, n = 10) was
      2.5 times higher than that in CM (52.2 +/- 3.2 fmol/mg protein, n = 6). These
      results indicate that there is a muscle layer-dependent difference of histamine
      induced response in the swine myometrium. In the LM layer, histamine acts on both
      H1 and H2 histamine receptors, and causes contraction (via H1 receptors at a low
      concentration) or relaxation (via H2 receptors at a high concentration in the
      presence of pyrilamine). However, histamine causes only a contraction in the CM
      layer, likely the result of the absence of H2 histamine receptors. Histamine
      induced contraction is conspicuous in the LM layer, because of the heterogeneous
      distribution of H1-receptors between LM and CM.

PMID- 9185085
TI  - Dexamethasone and flumethasone residues in milk of intramuscularly dosed cows.
AB  - A field study was performed to assess the level of drug residues in milk after
      therapeutic application of highly potent synthetic glucocorticoids. Dexamethasone
      was tested either as a crystalline suspension or as a combination of sodium
      phosphate and phenylpropionate esters. Intramuscular injection of these
      preparations in lactating dairy cows (60 micrograms dexamethasone/kg body wt)
      yielded drug residues in milk of up to 8.4 ng/mL 12 h after treatment. These
      dexamethasone residues fell to below 1.0 ng/mL within 3 days after treatment.
      Intramuscular injection of an aqueous flumethasone preparation (13.5
      micrograms/kg body wt) produced drug residues in milk in the range of 0.7-1.2
      ng/mL 12 h after treatment, whereas flumethasone was below the detection limit of
      0.23 ng/mL 2 days after administration. These results indicate that
      toxicologically significant residues may arise transiently in the milk during the
      first 2-3 days after intramuscular injection of synthetic glucocorticoids. Urine
      from the same animals contained 5- to 50-fold higher glucocorticoid
      concentrations than the corresponding milk samples. Thus, urine analysis appears
      to be an effective method to monitor the use of synthetic glucocorticoids in food
      producing animals.

PMID- 9185086
TI  - Pharmacokinetic study of dipyrone metabolite 4-MAA in the horse and possible
      implications for doping control.
AB  - The pharmacokinetic behaviour of dipyrone metabolite 4-MAA in serum was
      determined in seven horses of different breeds after a single intravenous dose
      administration. A biexponential formula was fitted to the serum concentration vs.
      time data. The median half-life of the elimination phase (t1/2 beta) was 4.85 h
      (range 5.04 h), the median volume of distribution (Vd(area)) was 1.85 L/kg (range
      3.2 L/kg) and median of total clearance was 4.0 mL/min/kg (range 2.3 mL/min/kg).

PMID- 9185087
TI  - Vaso-reactivity of isolated bovine intra-mammary artery to endogenous prostanoids
      and nitric oxide.
AB  - The modulatory role of locally produced cyclooxygenase products and endothelium
      derived nitric oxide in controlling vascular tone was investigated in bovine
      intra-mammary artery. Vascular reactivity initiated by vasoactive compounds,
      endothelin-1 (ET-1), bradykinin (BK), and substance P (SP) was measured
      isometrically in an isolated tissue bath. The effects of a cyclooxygenase
      inhibitor, indomethacin (10(-5) M) and an inhibitor of nitric oxide production, N
      omega-Nitro L-Arginine (L-NNA: 3 x 10(-4) M) were determined during agonist
      mediated responses. Indomethacin alone markedly enhanced vascular contraction
      produced by ET-1, while L-NNA did not. Inhibition of endothelium-derived nitric
      oxide synthesis by L-NNA, however, significantly attenuated BK- and SP-induced
      vascular relaxations, whereas indomethacin had slight influence. The potentiation
      between indomethacin and L-NNA in regulating vasomotor tone was not observed in
      this vascular bed. Thus, it appeared that both the cyclooxygenase and endothelium
      derived nitric oxide pathways participated in modifying vascular reactivity.
      Domination of one pathway over the other depended upon the agonist used to
      stimulate vascular tissue.

PMID- 9185088
TI  - Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs.
AB  - Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in
      tissue baths under isometric conditions. This contraction (approximately 50% of
      maximum: EC50) was relaxed completely with adrenoceptor drugs. The only exception
      was clenbuterol, where the degree of relaxation was approximately 90%. In all
      horses the EC50-value for isoprenaline (mean 1.6 x 10(-8) M) was less than that
      for adrenaline (mean 9.6 x 10(-8) M) and noradrenaline (mean 1.8 x 10(-6) M). The
      potency ratio was 1 < 6 < 110 which indicates that the beta 2-subtype dominates
      among the beta-adrenoceptors of equine airways. All preparations were also very
      sensitive to the specific and potent beta 2-receptor agonists clenbuterol (mean
      5.7 x 10(-9) M) and procaterol (mean 3.6 x 10(-10) M). No differences in EC50
      values due to age, sex and breed were observed in this material. The standard
      deviation of the mean EC50-values seems to be larger for the specific beta 2
      adrenoceptor agonists than for the unspecific. A reason for this could be
      differences in the pattern of the beta-adrenoceptor population.

PMID- 9185090
TI  - Lack of local anaesthetic efficacy of Sarapin in the abaxial sesamoid block
      model.
AB  - Sarapin is a distillate of the pitcher plant that has long been used in human and
      veterinary medicine for 'regional analgesia'. The mechanism of the reported
      analgesic response is unknown; however, the agent is purported to provide more
      effective analgesia for slow, chronic pain than for sharp, acute pain.
      Reportedly, Sarapin is also widely used as an analgesic agent in the horse,
      generally in combination with corticosteroids and other agents. To determine its
      local anaesthetic efficacy in the horse, we tested Sarapin in a unilateral
      abaxial sesamoid block model at two dose levels, 2 mL and 10 mL per site,
      respectively. Cutaneous pain was induced with a light/heat lamp, and analgesia
      was assessed by measuring the hoof-withdrawal reflex latency period. Neither dose
      of Sarapin altered hoof-withdrawal reflex latency in this experimental model
      tested over a two-week period. Based on the demonstrated efficacy of this local
      anaesthetic model, it seems clear that Sarapin has no significant classical local
      anaesthetic actions in the horse, and probably not in other species either.

PMID- 9185089
TI  - An assessment of the peripheral antinociceptive potential of remoxipride,
      clonidine and fentanyl in sheep using the forelimb tourniquet.
AB  - A modification of the intravenous regional anaesthesia technique was used to
      assess the peripheral antinociceptive effect of remoxipride, clonidine and
      fentanyl. Drugs administered intravenously via peripheral catheters were
      restricted to the distal limb and nociceptive threshold test site by prior
      inflation of a tourniquet proximal to both the catheter and a threshold-testing
      device. Lignocaine (1 mg/kg) induced peripheral antinociception during tourniquet
      inflation. Clonidine (6 micrograms/kg) only induced significant elevations in
      thresholds after tourniquet deflation. A low dose of remoxipride (2 mg/kg), which
      had no systemic antinociceptive effect, produced antinociception after its
      restriction to the periphery. Peripheral administration of saline and tourniquet
      induced restriction of blood flow to the distal limb did not alter threshold
      values. Peripheral administration of fentanyl was used to test a further
      modification of the injection protocol designed to reduce the incidence of
      leakage into the systemic circulation. Fentanyl administration (11.2
      micrograms/kg) failed to elicit an increase in thresholds when it was restricted
      to the distal limb test site. The contribution of a peripheral mechanism to the
      antinociception induced by systemic administration of a higher remoxipride dose
      (7.5 mg/kg) was investigated using an inflated tourniquet to exclude remoxipride
      from the periphery. Exclusion of remoxipride from the periphery reduced its
      antinociceptive effect, i.e. threshold values were lower than if remoxipride was
      allowed free access to the limb prior to tourniquet inflation. The technique
      described here was effective in demonstrating that the increase in
      noninflammatory nociceptive thresholds seen with clonidine and fentanyl is not
      peripherally mediated whilst that seen with remoxipride has a peripheral
      component.

PMID- 9185091
TI  - Tranquillization of cane rats (Thryonomys swinderianus) with a depot neuroleptic
      (pipothiazine palmitate).
AB  - Stress-induced self-trauma is a major cause of mortality among captive cane rats
      (Thryonomys swinderianus). Six subadult female cane rats were injected with a
      long-acting neuroleptic drug (pipothiazine palmitate 25 mg/kg), and an equal
      number were injected with isotonic saline. Their behaviour and reactions to
      stimuli were recorded daily. After 5 weeks, treated animals continued to display
      significantly less stress-related behaviour than the control group. In addition,
      two abbreviated studies were conducted. Eleven subadult males were treated
      identically to the females. Their behaviour was recorded for 1 week.
      Subsequently, 11 indocile animals on a commercial cane rat farm were tested for
      calmness, treated with pipothiazine and retested after 2.5 weeks. The results of
      these studies were similar to those in the female study. A significant taming
      effect was seen 30 days after a single treatment for all invasive or aggressive
      tests in treated cane rats, and no extrapyramidal effects were noted.
      Pipothiazine affected neither their alertness nor weight gain. However,
      substantial behavioural alteration requires the exposure of the animal to
      stressful stimuli during the treatment period. Pipothiazine palmitate decreases
      the stress experienced by cane rats, eases their transition to a new environment,
      makes them easier to handle and less likely to injure themselves.

PMID- 9185092
TI  - Disposition kinetics of albendazole in buffalo and cattle.

PMID- 9185093
TI  - Pharmacokinetics of long-acting oxytetracycline in fallow deer (Dama dama).

PMID- 9185094
TI  - The effect of epidural xylazine on halothane minimum alveolar concentration in
      ponies.

PMID- 9185095
TI  - The problem of edema formation and resolution.

PMID- 9185096
TI  - Edematous states: an overview.
AB  - What I have tried to describe in these brief introductory statements are the key
      elements stimulating renal sodium retention mediated by arterial underfilling, as
      illustrated by the volume repletion reaction (Fig. 3). They may be summarized by
      saying that edematous states characterized by underfilling-most notably systolic
      pump failure-represent, in fact, suicidal arterial filling. This point of view is
      illustrated in Figure 8. Essentially, as shown in Figure 8, the original
      reduction in filling of the arterial tree, by provoking both hemodynamic changes
      and diminished sodium avidity, has the net effect of increasing end diastolic
      volume and, for a time, cardiac output, but at two great expenses: an increased
      afterload and a an increased preload. In the end, these latter two effects
      produce a reduced ejection fraction which obviously propagates the syndrome of
      systolic failure. Thus, suicidal arterial filling represents a vicious cycle in
      which homeostatic mechanisms set into play an attempt to compensate for
      inadequate arterial filling, which inevitably leads to increasing degrees of
      cardiac dysfunction and, hence, to deterioration of the patient. I have enjoyed
      presenting these introductory remarks. I am certain that subsequent talks in this
      Conference will consider more explicitly the provocative issue of the
      "overfilling" hypothesis as a mechanism for sodium retention in edematous states
      such as the nephrotic syndrome and cirrhosis.

PMID- 9185097
TI  - Mechanism of action of diuretics.

PMID- 9185099
TI  - Pathogenesis of edema formation in the nephrotic syndrome.
AB  - The development of edema in the nephrotic syndrome has traditionally been viewed
      as an underfill mechanism. According to this view, urinary loss of protein
      results in hypoalbuminemia and decreased plasma oncotic pressure. As a result,
      plasma water translocates out of the intravascular space and results in a
      decrease in intravascular volume. In response to the underfilled circulation,
      effector mechanisms are then activated that signal the kidney to secondarily
      retain salt and water. While an underfill mechanism may be responsible for edema
      formation in a minority of patients, recent clinical and experimental findings
      would suggest that edema formation in most nephrotic patients is the result of
      primary salt retention. Direct measurements of blood and plasma volume or
      measurement of neurohumoral markers that indirectly reflect effective circulatory
      volume are mostly consistent with either euvolemia or a volume expanded state.
      The ability to maintain plasma volume in the setting of a decreased plasma
      oncotic pressure is achieved by alterations in transcapillary exchange mechanisms
      known to occur in the setting of hypoalbuminemia that limit excessive capillary
      fluid filtration. The intrarenal mechanism responsible for primary sodium
      retention is not yet known, but may involve tubular resistance to the natriuretic
      effect of atrial natriuretic peptide.

PMID- 9185098
TI  - Clinical complications of diuretic therapy.

PMID- 9185100
TI  - Physiologic role and diuretic efficacy of atrial natriuretic peptide in health
      and chronic renal disease.
AB  - In recent years, different clinical studies have provided new information on the
      pathophysiological role and diuretic effectiveness of atrial natriuretic peptide
      (ANP) in subjects with normal renal function and patients with chronic renal
      disease. Plasma ANP (pANP) was increased by infusion at the lowest doses ever
      tested in humans who were on low salt diet to the levels that the same subjects
      gained when on a normal salt diet; ANP accounted for at least 40% of the increase
      of natriuresis. Similarly, ANP appeared to be mainly involved in the
      physiological down-regulation of salt excretion (that is, during the shift from a
      normal to low-sodium diet). Interestingly, data have been also attained on the
      efficacy of ANP as diuretic agent when administered at a low nonhypotensive
      dosage in normals as well as CRF patients. Indeed, low-dose ANP promoted a marked
      increase of sodium excretion in CRF patients to the same levels observed in
      normals, likely because the renal patients exhibited a more marked pANP increment
      secondary to the lower renal catabolism of the infused hormone. Moreover,
      aldosterone suppression was greater in CRF patients with respect to normals.
      Furthermore, the fractional urinary excretion of cGMP increased more in CRF
      patients than in normals. Finally, ANP infusion augmented the urinary losses of
      the main solutes retained in CRF (urea, potassium, phosphorous) with a
      significant decrease in the plasma levels. Hence, ANP per se not only plays a
      significant role in the up- and down-regulation of sodium excretion in healthy
      state and chronic renal disease, but it may also be considered to be a powerful
      and unique diuretic agent in CRF at nonhypotensive dosages.

PMID- 9185101
TI  - Use of diuretics in chronic renal failure.
AB  - Patients with chronic renal failure retain Na+ and H2O, and they retain K- and
      acid. This disordered homeostasis results in hypertension, edema, hyperkalemia
      and acidosis. Diuretics may be used to favorably modify these disturbances.
      However, because of the limited filtered load of water and electrolytes, and the
      low renal blood flow, measures need to be taken to maximize the response to
      diuretics. These measures include: (a) the use of the most bioavailable drug,
      torasemide, when using the oral route; (b) the use of the drug with the least
      hepatic elimination, furosemide, when using the intravenous route; (c) the use of
      combinations of loop- and distal tubule-acting diuretics; (d) the use of the
      maximum effective diuretic dose; and (e) the use of repeated doses or constant
      infusion. In benefiting hypertension, vascular congestion and hyperkalemia
      diuretics appear to exert their effects not only on the kidneys but also on
      extrarenal sites, such as the vascular tree and the gastrointestinal tract. The
      use of diuretics, however, is not without complications, which include:
      intravascular volume depletion and azotemia, ototoxicity (when using loop-acting
      diuretics), hyperlipidemia, acute pancreatitis, hyperkalemia (when using K(+)
      sparing agents), and acidosis (when using carbonic anhydrase inhibitors).

PMID- 9185102
TI  - Diuretics in hypertension.
AB  - Despite the consistent reduction in the incidence of stroke and coronary events
      demonstrated in numerous clinical trials in young and elderly hypertensive
      subjects, the use of diuretics has declined as a first-line therapy in
      hypertension. The metabolic dose-dependent side effects and the increasing
      availability of new drugs appear the two main reasons for the decline. Although
      the neutral metabolic effects and the perception of a more physiological approach
      to hypertension has been advocated with the newer agents, no definite proof has
      been reported on the long-term effects on cardiovascular end-points. Many of
      adverse effects of diuretics can be limited by the use of low doses. For this
      reason, as well as their efficacy, safety, and cost-effectiveness, diuretics
      should remain a first-line therapy for hypertensive patients.

PMID- 9185103
TI  - Living on chronic hemodialysis between dryness and fluid overload.
AB  - The hydration state of a hemodialysis patient reflects the balance between fluid
      overload, normovolemia and underhydration. Since chronic volume overload enhances
      the cardiac mortality, and chronic underhydration carries the risk for dialysis
      associated hypotension, treatment for the deranged water homeostasis of
      hemodialysis patients needs to focus on an accurate assessment of dry body
      weight. Non-invasive methods such as echocardiography of the inferior caval vein
      diameter (ICVD) or conductivity measurements are considered as reliable
      techniques to estimate the hydration state of hemodialysis patients. The value of
      biochemical parameters for an adequate assessment of dry body weight remains
      controversial. In our study we have determined cyclic guanosine 3'5'
      monophosphate (cGMP) serum levels in 125 patients undergoing regular
      hemodialysis. Predialytic cGMP significantly decreased from 46.1 +/- 26.0 to 17.0
      +/- 9.3 pmol/liter post-dialysis (P < 0.001). In 35 patients cGMP level after
      hemodialysis remained > 20 pmol/liter, but non of these patients displayed any
      clinical signs of fluid overload. In a group of patients with normal heart
      function (N = 29) additional sonography of the ICVD revealed normovolemia in 16
      patients, underhydration in 5 patients and fluid overload in 4 patients. The
      respective post-dialytic mean cGMP level was significantly higher in the
      overhydrated group compared to normovolemic and underhydrated patients (25.3 +/-
      10.8 vs. 14.7 +/- 6.4 and 11.4 +/- 5.3 pmol/liter, P < 0.02). However, there was
      no significant correlation between cGMP level and ICVD (r = 0.5, NS). We conclude
      that there is no single parameter to define the adequate dry body weight of a
      hemodialysis patient. Our own data demonstrate the limitations using cGMP,
      particularly in estimating underhydration. ICVD and bioimpedance offer non
      invasive methods for both volume overload and underhydration, and seem to be
      reliable in the routine assessment of dry body weight.

PMID- 9185104
TI  - Pathogenesis of water and sodium retention in cirrhosis.
AB  - The pathogenesis of renal sodium and water retention in cirrhosis involves
      extrarenal mechanisms because when kidneys from cirrhotic patients are
      transplanted into persons with normal livers, renal sodium and water retention no
      longer occurs. Cirrhosis is accompanied by portal hypertension, which leads to a
      hyperdynamic circulatory state. The Peripheral Arterial Vasodilation Hypothesis
      incriminates a relative underfilling of the arterial vascular compartment, which
      leads to the same neurohumoral responses that occurs in low cardiac output.
      Activation of the renain-angiotensin-aldosterone axis and the sympathetic system
      as well as non-osmotic release of vasopressin are well documented in cirrhosis.
      This sequence of events results in renal water and sodium retention, failure to
      escape from the sodium-retaining effect of aldosterone, and renal resistance to
      atrial natriuretic peptide. Dilutional hyponatremia is the strongest predictor of
      the occurrence of hepatorenal syndrome. The pathogenesis of the peripheral
      arterial vasodilation is not completely elucidated, but there is evidence for a
      major role of nitric oxide (NO). Increased vascular NO production has been
      demonstrated in cirrhosis. In the rat model of cirrhosis, normalization of
      vascular NO production with a NOS inhibitor corrects the hyperdynamic
      circulation, improves sodium and water excretion, and decreases neurohumoral
      activation. This insight into the mechanism(s) of the peripheral arterial
      vasodilation in cirrhosis should provide new tools in the treatment of edema and
      ascites, a major cause of morbidity and mortality in cirrhosis.

PMID- 9185105
TI  - Plasma cAMP: a hepatorenal link influencing proximal reabsorption and renal
      hemodynamics?
AB  - The existence of a hepatorenal link is suggested by several pathophysiological
      observations (indirect actions of glucagon on the kidney, hepatorenal syndrome),
      but the nature of this link remains unidentified. We propose that extracellular
      circulating cyclic AMP could be this link. Cyclic AMP (cAMP) is the intracellular
      second messenger of glucagon (G) action in the liver, and this organ is known to
      release cAMP in the blood in relatively large amounts after G administration. On
      the other hand, the proximal tubule (mainly the pars recta) is known to take up
      cAMP through the organic acid transport system. We observed that the glucagon
      induced rise in phosphate excretion, which requires supraphysiologic
      concentration of G, was significantly correlated with the simultaneous rise in
      plasma cAMP and could be mimiked by i.v. infusion of cAMP alone. Moreover, we
      showed that a significant hyperfiltration (similar to that induced by
      supraphysiologic G) can be observed if cAMP (mimicking G-induced hepatic release)
      is coinfused with a much lower, physiologic, amount of G. Taken together, these
      observations suggest that: (1) cAMP is a hepatorenal link and that plasma cAMP
      permanently influences the intensity of reabsorption in the pars recta of the
      proximal tubule; and (2) that cAMP participates, in conjunction with G, to
      control GFR. Insulin is known to exert an inhibitory influence on G-induced cAMP
      release by the liver and will thus weaken the indirect (cAMP-mediated) influence
      of G on renal function. This "pancreato-hepatorenal cascade" may explain the
      natriuretic effects of G and antinatriuretic effects of insulin, and probably
      contributes to disturbances observed in some pathophysiological situations such
      as the edema of liver cirrhosis or hyperfiltration of diabetes.

PMID- 9185106
TI  - Sodium and water retention in heart failure: pathogenesis and treatment.
AB  - In congestive heart failure (CHF), low cardiac output decreases the fullness of
      the arterial circulation. This underfilling of the arterial vascular compartment
      unloads the baroreceptors, resulting in a sequence of events to maintain arterial
      circulatory integrity. Among them, the renin-angiotensin-aldosterone axis, the
      sympathetic nervous system, the non-osmotic release of vasopressin and the
      endothelins are activated to increase vascular resistance and enhance sodium and
      water renal retention. Simultaneously, vasodilatory and natriuretic substances
      such as the natriuretic peptides are activated to counterregulate these
      vasoconstrictors. In the initial phase of CHF, these events contribute to the
      cardiorenal adaptation. However, when CHF progresses, they become maladaptive and
      further depress vantricular performance and increase sodium and water retention.
      This vicious cycle of CHF provides the rationale for the use of neurohormonal
      antagonists in CHF. The beneficial effects of angiotensin converting enzyme
      inhibitors in CHF are well described. Vasopressin V1 receptor antagonists have
      been associated with peripheral vasodilation and improved cardiac function in
      some patients with CHF. In CHF animals, the vasopressin V2 receptor antagonist
      has been demonstrated to reverse the defect in water excretion. Bosentan, an
      endothelin antagonist, is associated with an increase of cardiac index in
      patients with CHF. A role for exogenous natriuretic peptides is also under
      investigation. Modulation of the neurohumoral systems associated with CHF opens a
      new perspective in the treatment of cardiac edema, principally by improving
      cardiac performance.

PMID- 9185107
TI  - Daily hemofiltration in severe heart failure.
AB  - We treated nine patients having severe heart failure (IV NYHA classification)
      with anuria resistant to diuretics who were on daily hemofiltration, and
      estimated their survival for a year. The total volume of liquids removed was
      estimated by means of an echographic determination of the caval collapsability
      index. Dry weight was obtained from 6 to 22 days. The fluid removed varied from
      10 to 35 liters. Five patients at the end of the therapy took up diuresis again
      and recovered their sensitivity to diuretics. Three of these patients went beyond
      the 12 months of survival, and two patients died earlier. Four patients did not
      show the resumption of diuresis and they continued with daily hemofiltration.
      Three survived over 20 weeks; one died after 15 weeks. We conclude that daily
      hemofiltration is useful in patients with severe heart decompensation in that it
      increases their survival rate.

PMID- 9185109
TI  - Brain edema: pathogenesis and therapy.
AB  - In the brain intravascular and interstitial spaces are separated by a highly
      specialized endothelial lining, which is the morphological substrate of the blood
      brain barrier (BBB). Under physiological conditions the BBB exerts rigid control
      of water soluble compounds moving from blood into brain and from brain into
      blood, respectively. Under pathological conditions such as trauma or ischemia, an
      increase in BBB permeability may occur that allows plasma constituents to escape
      into the brain tissue. This "opening" of the BBB may, at least in part, be due to
      a massive release of autacoids, which thus act as mediators of vasogenic brain
      edema. Five criteria have to be fulfilled by a given autacoid to be considered a
      mediator candidate: (i) a permeability-enhancing action under physiological
      conditions; (ii) a vasodilatory action; (iii) the ability of inducing vasogenic
      brain edema; (iv) an increase of concentration in tissue or interstitial fluid
      under pathological conditions; and (v) a decrease of brain edema by inhibiting
      the release or action of a given autacoid. Among the mediator candidates
      discussed, only bradykinin fulfills all these criteria. Histamine, arachidonic
      acid and free radicals, including nitric oxide, may also be considered mediator
      candidates of brain edema, but for each of these compounds evidence is less clear
      than for bradykinin. Although the concept of autacoids mediating brain edema is
      well established and supported by experimental data, it has not yet gained
      entrance into the clinics. Treatment of patients suffering from vasogenic brain
      edema is symptomatic and mainly concentrated on the control of intracranial
      pressure.

PMID- 9185108
TI  - Role of the heart surgeon in the emergency treatment of diuretic resistant edema
      in grades III-IV heart failure.
AB  - Acute or chronic valvular diseases, acute myocardial infarction and its
      complications, dilated cardiomyopathies, all may became the cause of heart
      failure leading to different degrees of cardiogenic edema. Today cardiac failure
      is treated from its the early stage by medical and/or surgical therapy.
      Thereafter, in a small population of patients, heart failure may became
      unresponsive to any kind of standard medical treatment. Conventional surgical
      procedures are often inadequate and carry a high risk of perioperative mortality.
      This study analyzes the outcome of 139 patients with end-stage cardiomyopathy who
      underwent heart transplantation between January 1988 and October 1996. We found
      that patients transplanted while on severe decompensation are at a higher
      perioperative mortality due to irreversible multi-organ failure. The study also
      suggests that the implantation of a left ventricle assist device as a bridge to
      transplantation is a promising maneuver for the most severe patients.

PMID- 9185110
TI  - Chronic arm edema following breast cancer treatment.
AB  - Chronic edema of the arm (postmastectomy edema, PME) is a common and incurable
      complication of breast cancer treatment, often developing without warning months
      or years later. Although the original cause of PME is damage to axillary lymph
      drainage routes by surgery and radiotherapy, many observations suggest that
      additional factors are involved. Recent attention has focused on the Starling
      forces in the skin and subcutis in PME. An important finding was that the protein
      concentration, and hence colloid osmotic pressure, of the subcutaneous
      interstitial fluid of the PMF arm is unexpectedly lower than in the unaffected
      arm, correlating negatively with the degree of swelling. There are several
      possible explanations for this, such as a rise in capillary filtration rate, or
      interstitial proteolysis. A systemic component to PME is suggested by the finding
      of a lower plasma protein concentration in affected women compared with a matched
      postmastectomy group without swelling. A recent study using intra-vital
      capillaroscopy has indicated that angiogenesis occurs in the skin in PME, and an
      increased capillary surface area for filtration could result in an increased
      fluid load on a compromised lymph drainage system. Further elucidation of the
      pathophysiological processes in PME, in particular the adjustments to Starling
      forces, will enable more effective therapy of this distressing condition.

PMID- 9185112
TI  - Edema in pregnancy.
AB  - During normal pregnancy total body water increases by 6 to 8 liters, 4 to 6
      liters of which are extracellular, of which at least 2 to 3 liters are
      interstitial. At some stage in pregnancy 8 out of 10 women have demonstrable
      clinical edema. There is also cumulative retention of about 950 mmol of sodium
      distributed between the maternal extracellular compartments and the product of
      conception. Thus, changes in factors governing renal sodium and water handling
      accompany alterations in local Starling forces whereby there is a moderate fall
      in interstitial fluid colloid osmotic pressure (COPi) and a rise in capillary
      hydrostatic pressure (Pc), as well as changes in hydration of connective tissue
      ground substance. Edema is a traditional criterion for diagnosing pre-eclampsia,
      but should no longer be used as its detection is not clinically useful. The role
      of diuretics in obstetric practice should be restricted to the management of
      pulmonary edema in pre-eclampsia. Volume expansion therapy in pregnancy runs the
      risk of pulmonary or cerebral edema, particularly in the immediate puerperium.
      Vulval edema and erythematous edema associated with deep venous thrombosis are
      rare but dangerous complications of pregnancy.

PMID- 9185111
TI  - Myxedema.
AB  - This review will discuss generalized myxedema as it develops in hypothyroidism.
      First, the precipitating conditions (thyroprivic trophoprivic + goitrous forms)
      and the clinical manifestations of thyroid hormone deficiency are presented.
      Pathobiochemical and pathophysiological factors that lead to the main
      manifestations include retention of fluid, retention of sodium and hyponatremia.
      In particular are primary and direct consequences of reduced thyroid hormone
      levels, and secondary or indirect consequences, such as cardiovascular and renal
      derangements. In hypothyroidism many biochemical disturbances result. Most
      important is the interstitial deposition of hydrophilic mucopolysaccharides,
      which in turn lead to fluid and Na retention and impairment of blood circulation
      and lymphatic drainage. Myxedema, therefore, is to a large extent a lymphatic
      edema. Hyponatremia is an indirect consequence of the lack of T3 and is directly
      caused by impaired renal Na reabsorption. Renal Na,K-ATPase is reduced in
      specific segments. The often discussed role of inappropriate elevation of
      circulating ADH does not seem to be a key factor in myxedema. Impaired capacity
      of renal water excretion is caused by reduced GFR. We discuss the time dependent
      development of the derangement of different organ systems, and include recently
      published biochemical results, according to which the lack of T3 interferes not
      only with the metabolism of numerous compounds of the interstitial matrix, but
      also with cell surface proteins and intracellular proteins of microfilaments.
      Finally, we refer briefly to pretibial myxedema in states of hyperthyroidism,
      that is, infiltrative dermopathy in Graves' disease, which is caused by poorly
      understood autoimmune processes.

PMID- 9185113
TI  - Neonatal edema.
AB  - Edema develops in the neonate from diverse clinical conditions; sometimes it
      heralds serious underlying disorders. In this review, we discuss the diagnosis
      and treatment of edema in the neonate.

PMID- 9185114
TI  - Edema in childhood.
AB  - There are two types of edema: localized edema and generalized edema. The causes
      of generalized edema in childhood are diverse. Formation of generalized edema
      involves retention of sodium and water in the kidney. The treatment of
      generalized edema depends on the primary etiology. Supportive nutritional and
      medical therapies are needed to prevent further edema. These and related features
      of edema in childhood are discussed in this review.

PMID- 9185115
TI  - Causes of edema in the intensive care unit.
AB  - Patients in emergencies necessitating treatment in the intensive care unit (ICU)
      often develop generalized gross edema. The usual scenario is that in the
      emergency situation characterized by hypotension and (impending) organ failure,
      large amounts of fluids are administered that subsequently cannot be excreted
      adequately, even if the emergency situation subsides to a more stable condition.
      Three main factors underlie the inadequate restoration of volume balance: (1)
      impaired edema mobilization, due to the negative influence on lymphatic flow of
      reduced muscle activity and increased central venous pressure by mechanical
      ventilation; (2) secondary renal sodium retention by circulatory impairment and
      hypotension caused by mechanical ventilation and by the cardiodepressant and
      vasodilatory effects of (endo-)toxemia; and (3) primary renal sodium retention by
      renal vasoconstriction and filtration impediment, due to a complex of systemic
      and intrarenal vasomodulator activation and intrarenal endothelitis, or acute
      renal failure. Edema itself, as far as impeding organ function and necessitating
      mechanical ventilation, may further perpetuate this difficult to handle and
      vicious circle.

PMID- 9185116
TI  - An unusual disorder of salt and water balance.

PMID- 9185117
TI  - Plants as a source of salt.
AB  - Ecological and ethnobotanical aspects of some halophylous plants are presented.
      These plants possess several morphophysiological adaptations to face salinity in
      their habitats. They are a source of salt and could represent new potential crops
      in saline environments.

PMID- 9185118
TI  - A history of edema and its management.
AB  - The obvious disfigurement caused by clinically evident edema has been a matter of
      medical concern for ages. Most of the early writings on the subject (Sumerian,
      Babylonian, Egyptian, Greek) center on dropsy, its causes and management. While
      reference to the heart is made in the ancient texts, much of the focus is on the
      abdominal (ascitic) accumulation of fluid. The role of the heart and "dropsy of
      the chest" began to be differentiated and attract attention sometime by the end
      of the seventeenth century, and were well appreciated by the eighteenth century.
      By the beginning of the nineteenth century the reports of John Blackall and
      Richard Bright provided new insight by differentiating dropsy into that of
      cardiac and renal origins. The role of salt, initially measured and thought in
      terms of its anion chloride, began to be appreciated by the middle to late
      nineteenth century. Its mobilization, however, remained problematic. The "cure de
      dechloruration", which gained fame by the end of the nineteenth century, was not
      always a successful undertaking. The treatment of dropsy, which centered on
      augmenting secretions (diaphoretics, purgatives) or mechanical removal of body
      fluids (bleeding, leeching, lancing), remained a frustrating and chancy
      undertaking for much of the time that medicine has had to deal with it. Although
      mercury had been advocated as a diuretic in the sixteenth century, even the
      organic mercurials that were introduced after World War II were limited in their
      effectiveness. The discovery of sulfanilamide-induced sodium bicarbonate diuresis
      in the late 1940s was to provide the first step in the new age of clinically
      effective diuretics, which began in the 1950s with the introduction of
      chlorothiazide, the first orally effective agent to mobilize sodium chloride. The
      subsequent introduction of more potent diuretics was made possible by concurrent
      advances in renal physiology and the understanding of the sodium handling by the
      kidney.

PMID- 9185119
TI  - A contribution to the history of common salt.
AB  - Salt has influenced human nutrition, health, politics, taxation, economy,
      freight, transport, and commerce throughout the ages. All human activities have
      been influenced by salt including economy, religious beliefs and practices, art,
      literature, psychoanalysis, superstitions, and exorcism. Salt is recognized as a
      symbol for friendship, hospitality, chastity, alliance, table fellowship,
      fidelity, fertility, blessing, curse and endurance, etc. The Bible is the first
      book of salt and contains no fewer than 24 references to this substance. In the
      Gospels the parable of salt is a central one. Many many church fathers have
      written on salt a substance, which up to 1969 was a relevant element in the rite
      of Baptism. This paper reviews the importance of common salt for human life, and
      by drawing from various scientific and literary sources makes a special
      discussion of its various symbolisms.

PMID- 9185120
TI  - The African polio vaccine-acquired immune deficiency syndrome connection.
AB  - Seroepidemiological, clinical and molecular findings suggest that the acquired
      immune deficiency syndrome virus human immunodeficiency virus-1 was introduced
      into the human species at the time (late 1950s) and in the geographic area
      (Zaire) in which millions of Africans were vaccinated with attenuated
      poliomyelitis virus strains that were produced in kidney tissue obtained from
      monkeys. Since monkeys not only harbor viruses that are remarkably similar to and
      genetically related to human immunodeficiency virus-1, but also served as tissue
      donors for the African polio vaccine, it is reasonable to suspect that a then non
      detectable monkey virus with human-1-like properties was unknowingly co-cultured
      with the attenuated poliovirus virus and subsequently administered to the
      vaccinees. The possibility of such a polio vaccine-acquired immune deficiency
      syndrome connection is a reminder of the unpredictable danger of artifically
      crossing natural species-barriers in biomedical laboratories.

PMID- 9185121
TI  - The possible role of peroxynitrite in Alzheimer's disease: a simple hypothesis
      that could be tested more thoroughly.
AB  - Alzheimer's disease is characterized by the development of a degenerative
      condition in the elderly, associated with dementia. Upon pathological
      examination, cerebral amyloid plaques are found which contain denatured protein
      or peptide material. The process of denaturation of protein requires the presence
      of excessive heat, organic solvents, or oxidizing acids (OA). It seems that only
      OA could produce these effects since the other two are not present in the
      disease. Macrophages can produce the anion of an oxidizing acid known as
      peroxynitrite (OONO). This material is formed from two free radical gases, namely
      superoxide anion [.O2]- and nitric oxide (.N = O). Although (OONO)- is very
      reactive (1000 times more oxidizing than hydrogen peroxide), its half life in
      solution is only 1 to 2 seconds. Therefore, when it oxidizes a substance (such as
      protein) peroxynitrite disappears. The brain contains cells called microglia
      which are produced from monocytes in the same way as other types of macrophages
      from the lung and liver etc. The macrophages from the lung (alveolar) and liver
      (Kupfer cells) produce large amounts of peroxynitrite when activated by particles
      (silica) or infectious agents (lipopolysaccharide or interferon). Microglia
      produce highly oxidizing substances as well, but no one has ever measured
      production of peroxynitrite from these cells. Assuming that microglia produce
      peroxynitrite, or other similar oxidants, anti-oxidant and anti-inflammatory
      drugs should be helpful in treatment of early forms of the disease. In addition,
      large doses of anti-oxidant vitamin C and vitamin E might be helpful to people
      with Alzheimer's disease.

PMID- 9185122
TI  - Oral famotidine: a potential treatment for children with autism.
AB  - Famotidine (Pepcid, a histamine-2 receptor blocker, is marketed for the treatment
      of peptic ulcer disease, gastroesophageal reflux, and the treatment of
      pathological hypersecretory conditions, including the Zollinger-Ellison syndrome.
      Recent reports indicate that it is also effective in relieving the deficit (or
      withdrawal) symptoms of adults with schizophrenia. Autism, a neuropsychiatric
      disorder which presents within the first few years of life, is defined by
      deficient social interaction, communication, language, play, and a markedly
      restricted repertoire of activities and interests. Similarities between the
      deficit symptoms of schizophrenia and the social deficit symptoms of autism
      suggest the hypothesis that famotidine may be useful in treating children with
      autism. Histamine serves as a neurotransmitter and neuromodulator in the brain.
      H2-receptors in the brain predominantly transmit inhibitory signals; when these
      receptors are stimulated in animals, spontaneous activity and exploratory
      behavior decrease; blockade of H2-receptors would therefore be expected to
      reverse this inhibition.

PMID- 9185123
TI  - Did the loss of endogenous ascorbate propel the evolution of Anthropoidea and
      Homo sapiens?
AB  - It has been previously theorized that free-radical reactions led to the first
      life on Earth, and their ability to randomly cause mutations may have
      subsequently led to the evolution of life. One of the most efficient free-radical
      quenchers is ascorbate, which most animals manufacture endogenously. It is
      generally believed that, approximately 25 million years ago, an ancestor of the
      Anthropoidea primate suborder, which includes Homo sapiens, lost the ability to
      produce its own ascorbate, and all descending species inherited this genetic
      defect. The first of three hypotheses presented here proposes that a genetic
      defect, caused by either free radicals or a virus, deleted the gene needed by
      Anthropoidea to manufacture endogenous ascorbate. The second hypothesis proposes
      that this evolutionary accident permitted large numbers of free radicals to
      remain metabolically unquenched. The third hypothesis proposes that the presence
      of these excessive free radicals increased the likelihood of free-radical-induced
      genetic mutations, and these mutations propelled the evolution of Anthropoidea,
      leading to Homo sapiens.

PMID- 9185124
TI  - Etiology of (CAG)n triplet repeat neurodegenerative diseases such as Huntington's
      disease is connected to stimulation of glutamate receptors.
AB  - Chronic neurodegenerative diseases with expanded, genetically unstable (CAG)n
      triplet repeats include Huntington's disease. It is hypothesized that pathology
      results from excessive stimulation of glutamate receptors by glutamine.

PMID- 9185125
TI  - Evolutionary sexology: the hypothesis of song and sex.
AB  - In subhuman mammalian species, lovemaps are homogeneous and are more or less
      biorobotically fixed, whereas in the human species they are emancipated from
      biorobotism and are personalized, idiosyncratic, and heterogenous-as, for
      example, in the paraphilias. The evolutionary sexological hypothesis described
      herein proposes that emancipation of all of the biorobotic mindbrain maps, the
      mating map included, was essential for, and coincident with the evolution of the
      human speechmap from the songmap. Accordingly the first human language was a love
      song rather than a howl of warning. The bare essentials of sexuoerotic arousal
      and response are in three categories: haptoerotic (cutaneous), morphoerotic
      (visual), and gnomoerotic (narrative).

PMID- 9185126
TI  - Medicine and evolution: time for a new paradigm?
AB  - The theory of Evolution is being invoked frequently in medicine to account for
      counter-intuitive findings such as programmed cell death in congestive heart
      failure and the fact that fever can prove both blessing or curse, depending on
      the circumstances. These and other examples of what might be called maladaptive
      adaptations are discussed, and it is suggested that human development may have
      reached a stage where the roles of mutation and selection are drastically
      changed. By creating an environment both mutagenic and protective, we have
      altered the balance between the two great driving forces of evolution, increasing
      the frequency of mutations and reducing the need for adaptation. As a result, new
      diseases have arisen and the whole evolutionary process seems to have lost some
      of its benevolence, no longer insuring the survival of the fittest. We must
      entertain the possibility that Darwin's theory cannot explain the last few
      millennia of human evolution and is now useful chiefly as an approximation
      applicable to very long periods of time.

PMID- 9185127
TI  - Human diversity, environmental adaptation and neural crest.
AB  - The relationship between anatomical/physiological traits, environmental
      adaptability and neural crest is described, and possible mechanisms leading to
      human diversity are suggested. It is concluded that environmental adaptation
      seems to be limited to those structures of neural crest origin.

PMID- 9185128
TI  - Prostaglandin D synthase (beta-trace protein): a molecular clock to trace the
      origin of REM sleep?
AB  - In 1965, Zuckerkandl and Pauling proposed a novel concept that some important
      molecules termed semantides, which carry the information of the genes or a
      transcript thereof, can be used as molecular clocks to trace evolutionary
      history. According to this concept, enzymes are designated as tertiary
      semantides, following genes (primary semantides) and the mRNA (secondary
      semantides). Based on this idea, I propose that prostaglandin D synthase (which
      has been demonstrated recently as identical to the beta-trace protein present in
      the cerebrospinal fluid of mammals) may serve as a molecular clock to trace the
      origin and evolution of rapid eye movement sleep in the vertebrates.

PMID- 9185129
TI  - Autistic disorder and the endogenous opioid system.
AB  - The elevated activity of brain opioids has been implicated in the pathogenesis of
      autistic disorder. Research on plasma and cerebrospinal fluid levels of
      endogenous opioids in subjects with autistic disorder has produced conflicting
      results. The author suggests that the level of brain opioid activity is a
      contributing but not the determining factor in the pathogenesis of autistic
      disorder. The author further suggests that the development of autistic disorder
      is related to the interaction between the endogenous opioid system and various
      neurotransmitter systems in the brain.

PMID- 9185130
TI  - Induction of interleukin-1 and glucocorticoid hormones by HIV promotes viral
      replication and links human chromosome 2 to AIDS pathogenesis: genetic mechanisms
      and therapeutic implications.
AB  - Human immunodeficiency virus may regulate its replication by stimulating the
      synthesis of interleukin-1. Interleukin-1, in turn, has the ability to stimulate
      the human immunodeficiency virus enhancer region. The human genes responsible for
      interleukin-1 and interleukin-1 receptor antagonist synthesis are located on the
      long arm of chromosome 2. Coincidentally, the trans-activation responsive
      ribonucleic acid element in the R region of the long terminal repeat of human
      immunodeficiency virus-1 has been found to interact directly with a factor
      present on the long arm of chromosome 2 to facilitate transactivation by the
      human immunodeficiency virus Tat protein. The human CD26 gene is also located on
      the long arm of chromosome 2. CD26 is a lymphocyte cell surface antigen that is
      stimulated by interleukin-1 and serves with CD4 as a coreceptor that interacts
      with the V3 loop in gp120 of human immunodeficiency virus. The human
      immunodeficiency virus-induced interleukin-1 excess, thus, serves human
      immunodeficiency virus by enhancing replication, and by increasing human
      immunodeficiency virus infectivity via activation of CD26. IL-1 also adversely
      affects acquired immune deficiency syndrome-related Kaposi's sarcoma. Several
      genetic treatments for human immunodeficiency virus infection are proposed.

PMID- 9185131
TI  - Apoptosis: mechanisms and relation to AIDS.
AB  - Infection with the human immunodeficiency virus (HIV) is considered to lead to
      the acquired immunodeficiency syndrome (AIDS) via the progressive loss of immune
      competence in the infected host. Recent research has highlighted that HIV may
      indirectly trigger an active cell suicide process, referred to as programmed cell
      death or apoptosis, that contributes to the decline in lymphocyte counts
      throughout the course of HIV infection. We review here the main host- and HIV
      related factors actively involved in inducing lymphocyte apoptosis. Among them,
      the relationships linking HIV, the oxidant/antioxidant balance in the cellular
      redox system, tumor necrosis factor (TNF) and lymphocyte-associated ceramide
      generated through the activation of sphingomyelin pathway are receiving growing
      consideration. Recognizing the importance of apoptosis in AIDS pathogenesis may
      have a great impact on the design of new strategies for the treatment of the
      disease. Available data indicate that antioxidant compounds exert antiapoptotic
      activity. These compounds, in our opinion, should be used in combination regimens
      with antiretroviral drugs in the treatment of HIV-infected subjects.

PMID- 9185132
TI  - Neurological episodes after minor head injury and trigeminovascular activation.
AB  - Children appear particularly susceptible to severe but reversible neurological
      symptoms and/or signs after minor head injury; these include headache, confusion,
      drowsiness, vomiting, hemiparesis, cortical blindness, or seizures.
      Significantly, these neurological episodes are not associated with any
      identifiable structural brain abnormality on neuro-imaging. We propose that the
      cause of this condition is a reactive hyperaemia, a 'benign hyperaemic
      encephalopathy' mediated via activation of the trigeminovascular system.

PMID- 9185134
TI  - A possible role for enzymes in tumour-cell invasion.
AB  - The complex molecular and cellular processes of metastatic invasion as well as
      the anti-invasion possibilities are summarized. Invasion by neoplastic cells is a
      major obstacle to successful cancer therapy. Enzymes such as hyaluronidase,
      sialyltransferase, urokinase-type plasminogen activator, plasmin, matrix
      metalloproteinases, and others, play central roles in the catabolism of
      extracellular matrix macromolecules. However, this process can be opposed by
      inhibitors of these enzymes. Both invasion (promoters) and anti-invasion factors
      (suppressors) need further investigation, to clarify the role of these factors in
      the aetiology and possibly in the treatment and prognosis of metastatic cancer.

PMID- 9185133
TI  - Glucosamine for psoriasis?
AB  - Amphiregulin and transforming growth factor-alpha, agonists for the epidermal
      growth factor receptor, are the major autocrine growth factors for cultured
      keratinocytes, and their substantial overexpression in psoriatic lesions suggests
      that they are crucial to the basal hyperplasia that characterizes psoriasis.
      Amphiregulin binds to heparin and related highly sulfated polysaccharides, and
      exogenous heparin blocks its growth factor activity, rationalizing previous
      reports that psoriasis responds to heparin therapy. Differentiating keratinocytes
      produce increased amounts of protein-bound as well as free-chain heparan
      sulfates, which may function physiologically as amphiregulin antagonists. By
      promoting keratinocyte synthesis of these heparan sulfates, glucosamine
      administration may inhibit amphiregulin function and thus provide therapeutic
      benefit in psoriasis. Concurrent ingestion of fish oil, by impeding the excessive
      activation of protein kinase C, may decrease keratinocyte production of
      amphiregulin and other autocrine growth factors, thus complementing the
      postulated benefits of glucosamine.

PMID- 9185135
TI  - Rationale and specifications for an automatic cardiac arrest-driven alarm and 911
      caller ID (ACADA/911).
AB  - The rationale and specifications for a permanent non-invasive cardiac monitoring
      device are described, including both an alarm and a device-initiated call (giving
      patient residence identification) to the emergency services number 911, if
      cardiac arrest is detected. This device may be useful for high-risk cardiac
      patients, who incur an unwitnessed cardiac arrest, by providing a prompt call and
      alarm for early initiation of bystander CPR, cardiac defibrillation (if
      necessary), advanced cardiac life-support, and early transfer of resuscitated
      patients to a hospital cardiac care unit. Unwitnessed cardiac arrest patients
      otherwise have a dismal prognosis because of prolonged circulatory arrest times
      and late initiation of defibrillation attempts. With out-of-home unwitnessed
      cardiac arrest, ACADA-911 specifications also include a cardiac arrest-triggered
      determination of the patient's location through a commercially inexpensive global
      positioning system device, whose output is transmitted to EMS via an attached
      cellular phone/priority call network. A randomized controlled study evaluation of
      the device is proposed.

PMID- 9185136
TI  - The enduring pneumococcus: unfinished business and opportunities for the future.

PMID- 9185137
TI  - Effect of antimicrobial use and other risk factors on antimicrobial resistance in
      pneumococci.
AB  - Penicillin-resistant and multi-resistant pneumococci have spread globally and
      reached high prevalence in many countries. Antimicrobial use is considered a
      major driving force for resistance, although the influence in the community has
      not been as clearly demonstrated. Other risk factors may be important, and only
      with a clear understanding of the risk factors can effective control measures be
      introduced. The main habitat of the pneumococcus is the nasopharynx of children.
      Carriage increases from birth and is maximal at pre-school age. Antimicrobial use
      in children is likely to have a significant influence on the susceptibility of
      pneumococci. Most studies looking for risk factors for resistance in pneumococci
      have identified antimicrobial use as a risk factor, especially the following
      aspects: ongoing, recent, repeated, frequent, and prophylactic antibiotic use.
      The effect of individual classes of antimicrobials has not been studied in detail
      but use of beta-lactam antibiotics and trimethoprim-sulpha has been associated
      with increased risk. Other risk factors are young age, nosocomial acquisition,
      prior hospitalization, and HIV infection. Day-care centers can facilitate the
      spread of resistant pneumococci and an Icelandic study showed that carriage of
      resistant pneumococci was associated with young age, domicile in an area with
      high antimicrobial consumption, recent antimicrobial use, frequent antimicrobial
      use, and use of trimethoprim-sulpha. The rapid increase of penicillin-resistant
      pneumococci in Iceland was met with propaganda against overuse of antimicrobials,
      which lead to reduction of antimicrobial use and subsequently a reduced incidence
      of penicillin-resistant pneumococci. This reduction may be related to reduced
      antimicrobial use. Reducing antimicrobial use should be considered important for
      programs aimed at reducing antimicrobial resistance.

PMID- 9185138
TI  - Epidemiology of pneumococcal serotypes and conjugate vaccine formulations.
AB  - The incidence of bacteremia and meningitis due to Streptococcus pneumoniae is
      highest among preschool-age children, particularly those < 2 years of age.
      Clinical trials of capsular polysaccharide vaccines among young children have
      been disappointing. Conjugation of bacterial polysaccharides to proteins can
      increase antibody responses following vaccination of young children. Most
      conjugate vaccines proposed to date have been seven-valent. To identify serotypes
      most commonly associated with infection in young children, we serotyped
      pneumococcal isolates submitted to the CDC through national surveillance from
      3884 children < 6 years old with pneumococcal bacteremia (n = 3169), meningitis
      (n = 401), or otitis media (n = 314) from 1978 to 1994. Seven serotypes (14, 6B,
      19F, 18C, 23F, 4, and 9V) accounted for 3045 (78%) isolates. A conjugate
      pneumococcal vaccine protecting against these seven serotypes and serologically
      cross-reactive serotypes could potentially prevent 86% of bacteremia, 83% of
      meningitis, and 65% of otitis media cases. The proportion of isolates covered by
      such a vaccine increased from 78% to 87% from 1978 to 1994. Of 70 isolates
      submitted during 1992-1994 which were nonsusceptible to penicillin (minimal
      inhibitory concentration [MIC] > 0.1 microgram/mL, 56 (80%) were among the seven
      most prevalent serotypes. All 21 isolates resistant to penicillin (MIC > or = 2.0
      micrograms/mL) were among these seven serotypes.

PMID- 9185139
TI  - Pan American Health Organization epidemiological surveillance network for
      Streptococcus pneumoniae.

PMID- 9185140
TI  - Distribution of capsular types and penicillin-resistance of strains of
      Streptococcus pneumoniae causing systemic infections in Argentinian children
      under 5 years of age. Streptococcus pneumoniae Working Group.
AB  - Streptococcus pneumoniae (SPN) is the most common cause of invasive infections in
      children, with high levels of mortality in developing countries. An increase in
      frequency of penicillin-resistant strains is reported in most parts of the world.
      A study was undertaken in Argentina and 5 other countries of the region, to
      determine the type distribution and penicillin resistance rate of SPN isolated
      from invasive infections in children less than 5 years old. Between June 1994 and
      March 1996, a total of 505 SPN isolated from sterile sites were collected from 15
      hospitals located in 9 cities of different geographic areas. Clinical and
      epidemiological data from 443 children were analyzed. Sixty five percent SPN were
      isolated from children less than 2 years old. Pneumonia was the clinical
      diagnosis in 58% of the cases, meningitis in 22%, and sepsis in 10.6%. Isolates
      were recovered from blood (51.2%), pleural fluid (22.7%), CSF (20.7%), and other
      sterile sites (5.4%). Thirty different pneumococcal capsular types were
      identified and the 10 most frequent in descending order were: 14, 5, 1, 6A/6B,
      7F, 9V, 19F, 19A, 16F y 23F, representing 89.3% of the total. Overall, 13.1% of
      isolates showed intermediate resistance to penicillin while 11.3% showed high
      resistance. Lethality was 8.8%, without correlation with penicillin-resistance
      and/or type. These result should be used in selecting the optimal combination of
      specific types for a conjugate vaccine, useful in children less than 2 years old
      and for considering therapeutic strategies for invasive pneumococcal infections.

PMID- 9185141
TI  - Prevalence of serotypes and antimicrobial resistance of streptococcus pneumoniae
      strains isolated from Brazilian children with invasive infections. Pneumococcal
      Study Group in Brazil for the SIREVA Project. Regional System for Vaccines in
      Latin America.
AB  - A laboratory surveillance study was developed in Brazil in 1993 to determine
      capsular types and antimicrobial susceptibility of Streptococcus pneumoniae
      strains. By studying 360 strains isolated from children with invasive infections
      in three different cities, 8 out of 34 types were identified as being the most
      prevalent and considered as the reference group for further analyses. This group
      comprised 77.7% of all strains studied, and includes the types 1, 5, 6A/B, 9V,
      14, 19F, 19A, and 23F. The prevalence of this reference group was significantly
      higher among strains isolated from children with pneumonia than meningitis.
      Similarly, this group was more prevalent among strains isolated from children 3
      to 6 years of age than from children under 2 years of age. Most strains (78.6%)
      were found to be susceptible to penicillin and only 1.4% showed high resistance
      to this antibiotic. However, intermediate resistance to penicillin was detected
      in 20% of the strains. This laboratory surveillance will be maintained and
      extended to other cities of Brazil to better define and monitor the trends of
      pneumococcal infections for proper control and prevention.

PMID- 9185142
TI  - Distribution of capsular types and antimicrobial susceptibility of invasive
      isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study
      Group in Colombia.
AB  - Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in
      the developing world. This study describes the type distribution and
      antimicrobial susceptibility of invasive pneumococcal isolates from Colombian
      children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional
      initiative designed to determine the ideal serotype composition of a protein
      polysaccharide pneumococcal conjugate vaccine for use in children less than 5
      years old in Latin America. In Colombia, during the study period, centres in
      Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive
      diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the
      clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The
      seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%),
      19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin
      (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and
      3.1% showing high level resistance. Among DSP isolates, 23% were also resistant
      to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to
      trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the
      isolates that have DSP. Penicillin resistance was associated with types 23F
      (53.8%) and 14 (25.6%). These data provides information on capsular types
      prevalent in Colombia that will not only allow the formulation of an ideal
      vaccine for the region but also reinforce the need for ongoing regional
      surveillance.

PMID- 9185143
TI  - Antimicrobial susceptibilities and capsular types of invasive Streptococcus
      pneumoniae isolated in children in Mexico City.
AB  - As part of the Sistema Regional de Vacunas (SIREVA) initiative, we conducted a
      surveillance study to determine the relative prevalence of capsular types of
      Streptococcus pneumoniae and antimicrobial susceptibility of invasive isolates in
      children less than 5 years old. We collected 220 isolates and found 33 of the 90
      known types, with type 23F as the most common followed by types 6A+B, 14, 19F,
      and 19A. High penicillin resistance was found in 49 strains (22.2%), 31 belonging
      to type 23F. Twenty-nine (13.1%) were resistant to erythromycin, 95 (43.1%) were
      resistant to chloramphenicol, and 24 (10.9%) were resistant to cefotaxime. No
      strains were resistant to vancomycin.

PMID- 9185144
TI  - Capsular type distribution and susceptibility to antibiotics of Streptococcus
      pneumoniae clinical strains isolated from Uruguayan children with systemic
      infections. Pneumococcus Study Group.
AB  - Children under 24 months of age are at high risk for serious infection with
      Streptococcus pneumoniae but they do not elicit effective immune responses to the
      currently available capsular polysaccharide vaccines. A polysaccharide protein
      conjugated vaccine involving the most frequent types has become an urgent need.
      To produce such a vaccine for Latin America, information on type distribution is
      required. Recently, Uruguay was 1 of the 6 countries in Latin America where
      surveillance for invasive pneumococcal infections in children under the age of 5
      years was carried out. Seventy percent of the 182 invasive S. pneumoniae isolates
      were recovered from patients under 24 months of age, and 19% were recovered from
      infants under 6 months. The 7 most frequent types were 14, 5, 1, 6B, 3, 7F, and
      19A; representing 80% of invasive isolates. Twenty-one types were identified, 16
      in pneumonia and 14 in meningitis. Resistance to penicillin increased during the
      study period, from 29% in 1994, to 40% in 1995-1996, mainly because of the spread
      of type 14 strains resistant to penicillin and trimethoprim/sulphamethoxazol (89%
      of resistant isolates). The high proportion of systemic pneumococcal infections
      recorded in patients under 24 months of age and the increasing resistance of
      these agents to first-choice antibiotics point to an urgent need for a capsular
      polysaccharide protein conjugated vaccine.

PMID- 9185145
TI  - Bacteriophages of Streptococcus pneumoniae: a molecular approach.
AB  - We have characterized four families of pneumococcal phages with remarkable
      morphologic and physiological differences. Dp-1 and Cp-1 are lytic phages,
      whereas HB-3 and EJ-1 are temperate phages. Interestingly, Cp-1 and HB-3 have a
      terminal protein covalently linked to the 5' ends of their lineal DNAs. In the
      case of Dp-1, we have found that the choline residues of the teichoic acid were
      essential components of the phage receptors. We have also developed a
      transfection system using mature DNAs from Dp-4 and Cp-1. In the later case, the
      transfecting activity of the DNA was destroyed by treatment with proteolytic
      enzymes, a feature also shared by the genomes of several small Bacillus phages.
      DNA replication was investigated in the case of Dp-4 and Cp-1 phages. The
      terminal protein linked to Cp-1 DNA plays a key role in the peculiar mechanism of
      DNA replication that has been coined as protein-priming. Recently, the linear
      19,345-bp double-stranded DNA of Cp-1 has been completely sequenced, several of
      its gene products have been analyzed, and a complete transcriptional map has been
      ellaborated. Most of the pneumococcal lysins exhibit an absolute dependence of
      the presence of choline in the cell wall substrate for activity, and phage lysis
      requires, as reported for other systems, the action of a second phage-encoded
      protein, the holin, which presumably forms some kind of lesion in the membrane.
      The two lytic gene cassettes, from EJ-1 and Cp-1 phages, have been cloned and
      expressed in heterologous and homologous systems. The finding that some lysogenic
      strains of Streptococcus pneumoniae harbor phage remnants has provided important
      clues on the interchanges between phage and bacteria and supports the view of the
      chimeric origin of phages.

PMID- 9185146
TI  - Molecular bases of three characteristic phenotypes of pneumococcus: optochin
      sensitivity, coumarin-sensitivity, and quinolone-resistance.
AB  - Streptococcus pneumoniae is uniquely sensitive to amino alcohol antimalarials in
      the erythro configuration, such as optochin, quinine, and quinidine. The protein
      responsible for the optochin (quinine)-sensitive (Opts, Qins) phenotype of
      pneumococcus is the proteolipid c subunit of the FzeroF1 H(+)-ATPase. OptR/QinR
      isolates arose by point mutations in the atpC gene and produce different amino
      acid changes in one of the two transmembrane alpha-helices of the c subunit. In
      addition, comparison of the sequence of the atpCAB genes of S. pneumoniae R6
      (Opts) and M222 (an OptR strain produced by interspecies recombination between
      pneumococcus and S. oralis), and S. oralis (OptR) revealed that, in M222, an
      interchange of atpC and atpA had occurred. We also demonstrate that optochin,
      quinine, and related compounds specifically inhibited the membrane-bound ATPase
      activity. Equivalent differences between Opts/Qins and OptR/QinR strains, both in
      growth inhibition and in membrane ATPase resistance, were found. Pneumococci also
      show a characteristic sensitivity to coumarin drugs, and a relatively high level
      of resistance to most quinolones. We have cloned and sequenced the gyrB gene, and
      characterized novobiocin resistant mutants. The same amino acid substitution (Ser
      127 to Leu) confers novobiocin resistance on four isolates. This residue position
      is equivalent to Val-120 of Escherichia coli ryGB, a residue that lies inside the
      ATP-binding domain but is not involved in novobiocin binding in E. coli, as
      revealed by crystallographic data. In addition, the genes encoding the ParC and
      ParE subunits of topoisomerase IV, together with the region encoding amino acids
      46 to 172 (residue numbers as in E. coli) of the pneumococcal ryGA subunit, were
      characterized in respect to fluoroquinolone resistance. The gyrA gene maps to a
      physical location distant from the gyrB and parEC loci on the chromosome.
      Ciprofloxacin-resistant (CpR) clinical isolates had mutations affecting amino
      acid residues of the quinolone resistance-determining region of ParC (low-level
      CpR), or in both resistance-determining regions of ParC and GyrA (high-level
      CpR). Mutations were found in residue positions equivalent to Ser-83 and Asp-87
      of the E. coli GyrA subunit. Transformation experiments demonstrated that
      topoisomerase IV is the primary target of ciprofloxacin, DNA gyrase being a
      secondary one.

PMID- 9185147
TI  - Disequilibria in the distribution of rpoB alleles in rifampicin-resistant M.
      tuberculosis isolates from Germany and Sierra Leone.
AB  - The effectiveness of culture-independent resistance predictions by molecular
      techniques is dependent on the number and the frequency of accessible resistance
      associated genomic mutations. We have characterized an rpoB gene region involved
      in rifampicin resistance in 49 Mycobacterium tuberculosis isolates resistant to
      rifampicin from Germany and Sierra Leone. The determined frequencies of mutations
      differed between both countries of origins as well as with respect to previously
      reported distributions of resistance mutations. It is concluded that at least for
      some isolates the acquisition of mutations leading to rifampicin resistance in
      clinical samples of M. tuberculosis is a non-random process which may lead to a
      geographical and temporal dependence of the sensitivities of molecular typing
      techniques for rifampicin resistance predictions.

PMID- 9185148
TI  - The pneumococcal cell wall degrading enzymes: a modular design to create new
      lysins?
AB  - Autolysins are enzymes that degrade different bonds in the peptidoglycan and,
      eventually, cause the lysis and death of the cell. Streptococcus pneumoniae
      contains a powerful autolytic enzyme that has been characterized as an N
      acetylmuramoyl-L-alanine amidase. We have cloned the lytA gene coding for this
      amidase and studied in depth the genetics and expression of this gene, which
      represented the first molecular analysis of a bacterial autolysin. Two
      observations have been fundamental in revealing further knowledge on the lytic
      systems of pneumococcus: (a) The well-documented dependence of the pneumococcal
      autolysin on the presence of choline in the cell wall for activity, and (b) the
      early observation that most pneumococcal phages also required the presence of
      this amino-alcohol in the growth medium to achieve a successful liberation of the
      phage progeny. We concluded that choline would serve as an element of strong
      selective pressure to preserve certain structures of the host and phage lytic
      enzymes which should lead to sequence homologies. We constructed active chimeras
      between the lytic enzymes of S. pneumoniae and its bacteriophages using genes
      that share sequence homology as well as genes that completely lack homologous
      regions. In this way, we demonstrated that the pneumococcal lytic enzymes are the
      result of the fusion of two independent functional modules where the carboxy
      terminal domain might be responsible for the specific recognition of choline
      containing cell walls whereas the active center of these enzymes should be
      localized in the N-terminal part of the protein. The modular design postulated
      for the pneumococcal lysins seems to be a widespread model for many types of
      microbial proteins and the construction of functional chimeric proteins between
      the lytic enzymes of pneumococcus and those of several gram-positive
      microorganisms, like Clostridium acetobutylicum or Lactococcus lactis, provided
      interesting clues on the modular evolution of proteins. The study of several
      genes coding for the lytic enzymes of temperate phages of pneumococcus also
      highlighted on some evolutionary relationships between microorganisms. We suggest
      that lysogenic relationships may represent a common mechanism by which pathogenic
      organisms like pneumococcus should undergo a rapid adaptation to an evolving
      environment.

PMID- 9185149
TI  - Advances in the microscopy of osteoarthritis.
AB  - This review describes recent contributions made by microscopy to the
      understanding of osteoarthritis, a clinical syndrome the pathological features of
      which are well defined by classical white light microscopy. The fluorescence and
      reflected light, conventional and scanning optical microscopy of excised
      osteoarthritic tissue preparations, from human and animal sources, has enabled
      the identification of cell proteins such as S100, of matrix components such as
      the proteoglycans and collagens, and of adhesion molecules including fibronectin,
      the integrins and tenascin. Comparable microscopic studies have been made of cell
      and tissue culture preparations of osteoarthritic cartilage and synovium.
      Scanning optical microscopy also allows the rapid measurement, in hydrated
      osteoarthritic tissues, of cell density, cell size, surface roughness and other
      parameters. The importance of water in sustaining the physical attributes of
      cartilage is accepted and new forms of electron microscopy can play important
      parts in the study of unfixed osteoarthritic cartilage. These methods include the
      low temperature scanning electron microscopy and electron probe x-ray
      microanalysis of hydrated bulk material and the high resolution transmission
      electron microscopy of low temperature replicas of cartilage surfaces.
      Understanding of osteoarthritis has been facilitated by these advances and will
      continue to be enhanced as new techniques of microscopy evolve.

PMID- 9185150
TI  - Ultrastructure of adult human articular cartilage matrix after cryotechnical
      processing.
AB  - The ultrastructure of adult human articular cartilage matrix is reexamined in
      tissue processed according to recently improved cryotechniques [Studer et al.
      (1995) J. Microsc., 179:321-332]. In truely vitrified tissue, a network of fine
      cross-banded filaments (10-15 nm in diameter) with a periodicity characteristic
      of collagen fibrils is seen throughout the extracellular substance, even within
      the pericellular compartment, which has hitherto been deemed free of such
      components. Proteoglycans fill the interstices between these entities as a
      homogeneously distributed granular mass; they do not manifest a morphologically
      identifiable reticular structure. Longitudinally sectioned collagen fibrils
      exhibit variations in thickness and kinking; they tend to align with their
      periodic banding in register and are frequently seen to split or fuse along their
      longitudinal course. The tendency of fibrils to form bundles is greater in deeper
      zones than in more superficial ones. A duality in the orientation of fibrils and
      fibril bundles is observed within the interterritorial matrix compartment:
      superimposed upon the well-characterized arcade-like structure formed by one
      subpopulation is another, more randomly arranged one. The classical concepts of
      matrix organization thus need to be modified and refined to encompass these
      findings.

PMID- 9185151
TI  - The contribution of quantitative confocal laser scanning microscopy in cartilage
      research: chondrocyte insulin-like growth factor-1 receptors in health and
      pathology.
AB  - The use of immunohistochemical detection techniques and fluorescent molecular
      probes in light and fluorescence microscopy allows accurate and specific analysis
      of a great variety of cell and tissue components. However, when staining yields
      only low intensity levels, serious problems may arise with discrimination of
      specific signals against background staining. This problem is often inherent with
      articular cartilage research. Application of confocal laser scanning microscopy
      (CLSM) can circumvent these problems. The CLSM collects images that are almost
      free of out-of-focus signals, which results in improved spatial resolution and
      discrimination as compared with conventional microscopy. Moreover, CLSM allows
      optical sectioning of specimens and three-dimensional reconstruction of the
      microscopical object. Quantitative evaluation of microscopical images is hampered
      by out-of-focus signals because they interfere with specific signals in the
      image. Interference of these nonspecific signals can be diminished by application
      of CLSM; in CLSM only one single point in microscopical objects is illuminated at
      any time and this point is then imaged into the pinhole at the entrance of the
      photo-detector and subsequently digitized. The present review is a discussion of
      the present state of the art in digital imaging with the use of CLSM in cartilage
      research. This discussion includes aspects such as sensitivity, specificity,
      spatial resolution and accuracy of quantitative analysis in microscopical
      immunofluorescent objects.

PMID- 9185152
TI  - Scanning electron microscopy of "fibrillated" and "malacic" human articular
      cartilage: technical considerations.
AB  - Specimens of articular cartilage from human knees with gross evidence of malacia
      (dull appearance and/or softness) or fibrillation (exposed fibrous strands and/or
      staining with India ink) were prepared for scanning electron microscopy (SEM) and
      compared to cartilage from apparently intact regions. Vertical cryofractures were
      made through the center of each specimen, so the matrix collagen structure and
      its relationship to surface features could be examined. Soft, dull, malacic
      cartilage was characterized by the presence of numerous clefts among the collagen
      fibers within the most superficial region of the cartilage. In one form of this
      condition, these clefts did not extend through the articular surface. In a second
      form, usually observed where the tangential zone was normally thin or absent, the
      free ends of radial collagen fibers were exposed, but the deeper layers were
      intact. Two forms of fibrillation were also identified. The first is created by
      separation of the superficial lamellae which curl up from the tangential layer
      and form frondlike projections above the normal plane of the joint surface. In
      the second, deep radial fibers are exposed by vertical fissures. This second form
      is associated with advanced damage to the joint. The early stages of cartilage
      failure are characterized by debonding among the major collagen fiber tracts.
      This process may initiate in the deep tangential zone where the radial fibers
      cross into the surface. The patterns of the degenerative changes are dictated by
      the original architecture of the collagen matrix. The microscopic findings do not
      correlate adequately with conventional gross grading. SEM provides useful
      information about injured articular cartilage.

PMID- 9185153
TI  - Osteoarthritis in the temporo-mandibular joint (TMJ) of aged mice and the in
      vitro effect of TGF-beta 1 on cell proliferation, matrix synthesis, and alkaline
      phosphatase activity.
AB  - The temporo-mandibular joint of aged mice develops osteoarthritic (OA)
      degenerative lesions. Adult chondrocytes have a low rate of cell replication, and
      cartilage repair potential is very limited. One of the major problems in OA is
      the low rate of matrix synthesis and the inability of the chondrocytes to exceed
      the rate of matrix degradation. These combined factors lead to the overall
      destruction of the cartilage as seen in OA. Cartilage degradation is mediated by
      elevated proteolytic activity of enzymes. Among the enzymes degrading cartilage
      are the metalloproteinases, stromelysin and collagenase. Other proteinases that
      may potentially participate in matrix degradation are the lysosomal enzymes
      cathepsin B, D, and L, and acid phosphatase. On the other hand, alkaline
      phosphatase (ALP) is an enzyme that has been shown to be a marker for anabolic
      activity in skeletal tissues such as bone and cartilage. The cartilage of the
      mandibular condyle in the T-M-J from aged mice reveals OA lesions. An overall
      reduction of cell proliferation and sulfated proteoglycan synthesis has been also
      shown in this joint. In the present study the effects of hTGF-beta on the
      stimulation of DNA and sulfated GAG synthesis and ALP activity were studied.
      Mandibular condyle cartilage obtained from 12-month-old ICR male mice were
      cultured in BGJb serum-free medium for 24-72 hours, supplemented with 0.1-10
      ng/ml hTGF-beta 1. 3H-thymidine and 35S-sulfate were added for the last 24 hours
      of the culture and their incorporation into DNA and sulfated GAGs respectively,
      as well as the activity of ALP, were determined. Results indicated that hTGF-beta
      1 enhanced the incorporation of both 3H-thymidine and of 35S-sulfate into
      cartilage cultures of aged mice, and also induced ALP activity. It thus appeared
      that in OA degenerating articular cartilage, the chondrocytes could be stimulated
      in vitro to proliferate and to synthesize new matrix, thus indicating induced
      anabolic activity in the tissue.

PMID- 9185154
TI  - The interaction of the zone of calcified cartilage and subchondral bone in
      osteoarthritis.
AB  - The zone of calcified cartilage (ZCC) forms an important interface between
      cartilage and bone for transmitting force, attaching cartilage to bone, and
      limiting diffusion from bone to the deeper layers of cartilage. The height of the
      ZCC is a relatively constant percent of articular cartilage and the height is
      maintained by a balance between progression of the tidemark into the
      unmineralized cartilage and changing into bone by vascular invasion and bony
      remodeling. During its formation, the cells that form the ZCC have properties
      similar to the cells of the growth plate. In the adult, the ZCC becomes quiescent
      but not inactive. The ZCC may be reactivated in osteoarthritis and may
      progressively calcify the unmineralized cartilage. This might contribute to
      cartilage thinning which would increase the concentration of forces across the
      uncalcified cartilage leading to more damage. Although the subchondral bony plate
      remodels extensively in osteoarthritis, there is little evidence that a change in
      the biomechanics of the plate directly initiates the osteoarthritic process in
      cartilage. However, increased repair by endochondral ossification of vertical
      cracks in the ZCC that penetrate into the marrow space could contribute to
      progression via changes in the ZCC.

PMID- 9185155
TI  - Cartilage and subchondral bone interaction in osteoarthrosis of human knee joint:
      a histological and histomorphometric study.
AB  - The present study has focused on the cartilage-bone interrelationships in the
      progression of osteoarthrosis in human knees. Eleven tibial condyles with
      osteoarthrosis were analyzed by histology and bonemorphometry. The data were
      evaluated according to the grade of joint cartilage degeneration in distinct
      areas of the tibial condyle. The bone morphometric data were also analyzed by the
      depth of subchondral bone. A parallel relationship between the bone volume/bone
      formation activity and the Mankin's grade of cartilage degeneration was observed
      in both medial and lateral condyles. In the lateral condyle, there was
      correlation among progression of cartilage degeneration and trabecular and
      osteoid thickness and bone formation activity. Osteoblasts and osteoclasts were
      most abundant in the external areas of the medial condyles. Bone resorption
      activity in the medial condyle was found only in the external and intermediate
      areas, but it was extremely low in all areas of the lateral condyle. The values
      of bone volume in relation to depth were highest in the superficial layer with a
      decrease as the depth increased in both condyles. The bone formation activity was
      high in the superficial layer of the lateral condyle, whereas in the medial
      condyle, it was high in the layer between 500 and 1,500 microns of depth. The
      bone volume and bone formation activity were higher in all layers of the medial
      condyle in comparison with the lateral condyle. The bone resorption activity was
      low in the superficial layer of the medial condyle as compared with deeper
      layers. These results suggested that the joint cartilage degeneration is
      influenced by the remodeling of the underlying subchondral bone.

PMID- 9185156
TI  - The involvement of subchondral mineralized tissues in osteoarthrosis:
      quantitative microscopic evidence.
AB  - This paper reviews evidence for the role of subchondral bone and calcified
      cartilage in the initiation and progression of osteoarthrosis (OA). There is
      consensus that OA is characterized by subchondral sclerosis, but disagreement
      about whether bone changes are concurrent with, primary to, or secondary to
      cartilage deterioration. Clinical observation suggests that bone density and
      cartilage fibrillation are inversely related. Evidence from the rabbit impulsive
      loading model is consistent with early bone changes, but evidence from other
      models of subchondral stiffening, such as the sheep metallic implant model, do
      not strongly support this idea. However, evidence from tibial angulation models
      and from the Pond-Nuki (anterior cruciate ligament resection) model show evidence
      that bone changes precede cartilage fibrillation temporally, and are associated
      spatially within a single joint. Evidence is also presented for the importance of
      calcified cartilage changes in pre-disposing the joint towards progression to OA.
      Microdamage accumulation and repair by vascular invasion may be a component of
      the pathogenesis of OA in some cases, but more work is needed to demonstrate this
      conclusively. We conclude that changes in the subchondral mineralized tissues are
      not required for initiation of cartilage fibrillation, but may be necessary for
      progression, and that only changes in bone and calcified cartilage close to the
      joint are significant to the disease process.

PMID- 9185157
TI  - Bone density and local growth factors in generalized osteoarthritis.
AB  - Osteoarthritis is usually considered to be a primary disorder of chondrocyte
      function with secondary changes in bones. However, a defect in the subchondral
      bone resulting in loss of its shock absorbing capacity could transfer the stress
      of loading directly to the articular cartilage with secondary changes in the
      cartilage. Review of histomorphometric and bone densitometric studies at sites of
      osteoarthritis at the hip or knee revealed that cartilage fibrillation could not
      be dissociated from bony changes even in the earliest stages of osteoarthritis
      and that subchondral trabeculae are thickened and more spaced in osteoarthritis.
      Microfractures of subchondral trabecular bone were less frequently seen in
      osteoarthritis compared to controls. Changes of the tidemark were found to be
      multiform and metabolically active in the osteoarthritic process. Endochondral
      ossification depletes the calcified cartilage at the cartilage/bone interface and
      the tidemark has been thought of as a calcification front advancing in the
      direction of non-calcified cartilage. Duplication of the tidemark is cited as
      evidence of this advancement. In the few experimental animal studies of
      subchondral bone in osteoarthritis, thicker trabeculae which were closer together
      were found in guinea pigs already when only mild cartilage changes were present.
      In the dog, with cruciate ligament transection, changes in bone were later than
      in the cartilage, but the changes in bone could still contribute to the
      progression of osteoarthritis. To study if bone changes may precede injury to the
      cartilage and if metabolic and systemic influences can also alter the subchondral
      bone, rendering it less able to withstand normal mechanical stresses, bone at
      different sites in the body has been studied extensively by the authors.
      Epidemiological and case control studies have revealed that osteoarthritis cases
      have more bone at all sites than expected and that bone in cases with generalized
      osteoarthritis shows both quantitative and qualitative differences, including
      increased contents of growth factors and hypermineralization. These findings
      suggest that a more generalized bone alteration may be the basis of the
      pathogenesis of osteoarthritis.

PMID- 9185158
TI  - Sex differences in the effects of gonadectomy and acute swim stress on GABAA
      receptor binding in mouse forebrain membranes.
AB  - Gonadectomy of male mice resulted in a significant increase in GABAA receptor
      binding in forebrain membranes at GABA concentrations of 100-1000 nM, whereas
      gonadectomy of female mice resulted in no significant change in such binding.
      Acute swim stress (3 min swim at 32 degrees C) in gonadectomised female mice
      resulted in a significant increase in GABAA receptor binding in forebrain
      membranes at GABA concentrations of 400-1000 nM and in the plasma levels of
      corticosterone, whereas this stress produced no significant change in such
      binding or steroid levels in gonadectomised male mice. The surgical stress of
      sham gonadectomy produced significant increases in GABAA receptor binding in
      forebrain membranes at GABA concentrations of 100-1000 nM in both sexes, such
      that the acute swim stress induced increase in GABAA receptor binding in
      unoperated females is not observed. Hormone replacement studies in swim stressed
      gonadectomised females indicate that intraperitoneal injection of oestrogen (beta
      oestradiol, 10 micrograms) or progesterone (6 alpha-methyl-17 alpha-hydroxy
      progesterone acetate, 1 mg) significantly decreased GABAA receptor binding in
      forebrain membranes at GABA concentrations of 100-1000 nM compared to swim
      stressed, gonadectomised females injected with the sesame oil vehicle. The
      injection of a combination of oestrogen (1 microgram) and progesterone (0.1 mg)
      produced a greater reduction in GABAA receptor binding than the injection of
      either steroid hormone alone. These results indicate that, in addition to
      neurosteroids and corticosteroids, gonadal steroids contribute to the modulation
      of GABAA receptor binding in the brains of male and female mice.

PMID- 9185159
TI  - Expression of beta 1-4 N-acetylgalactosaminyltransferase gene in the developing
      rat brain and retina: mRNA, protein immunoreactivity and enzyme activity.
AB  - The developmental pattern of expression of the UDP-GalNAc:GM3 N
      acetylgalactosaminyltransferase (GalNAc-T) gene was examined in the rat brain and
      retina. A GalNAc-T cDNA cloned from a rat olfactory bulb cDNA library was used as
      a probe for Northern blot and in situ hybridization experiments and a rabbit
      polyclonal antibody to rat GalNAc-T peptide was used for Western blot analysis.
      In Northern blot experiments, a single approximately 3 kb transcript was detected
      both in brain and retina. In brain, the abundance of this transcript increased
      from E15 to PN1-5 and then declined while, in retina, it increased steadily from
      PN1 to PN13-24. The developmental trends of GalNAc-T mRNA expression, GalNAc-T
      immunoreactive protein and GalNAc-T activity were comparable in brain. In retina,
      however, GalNAc-T activity and GalNAc-T peptide immunoreactivity followed
      developmental patterns that were similar between them and different from that of
      the specific mRNA. Results suggest that post-transcriptional controls of the
      GalNAc-T gene expression operate in the rat CNS, which are particularly evident
      in retina. The expression of the GalNAc-T gene in glial and neuronal cells was
      examined in rat retina cell cultures by in situ hybridization. The GalNAc-T mRNA
      was abundant in GM1+/GD3+ neurons and almost absent in the flat, GM1-/GD3+ Muller
      glia-derived cells.

PMID- 9185160
TI  - Functional coupling of Gi subtype with GABAB receptor/adenylyl cyclase system:
      analysis using a reconstituted system with purified GTP-binding protein from
      bovine cerebral cortex.
AB  - A single molecular species of GTP-binding protein (G protein) has been purified
      from the bovine cerebral cortex. The immunoblot analysis indicated that the
      isolated G protein might be Gi1 or Gi2 but not Go, since it was reacted by
      specific antibodies, anti-Gi alpha 1-2 and anti-Gi alpha 1-1, but not anti-Go
      alpha. When the Gi protein was reconstituted into phospholipid vesicles with
      partially purified GABAB receptor and adenylyl cyclase, the stimulation of GABAB
      receptor by its agonists induced the inhibition of forskolin-stimulated cAMP
      accumulation. This GABA-induced inhibition was abolished by CGP 55845A, an
      antagonist of GABAB receptor. These results suggest that a Gi subtype, which was
      suggested to correspond to Gi1 or Gi2 may be functionally coupled with GABAB
      receptor/adenylyl cyclase system.

PMID- 9185161
TI  - Levels of dynorphin peptides in the central nervous system and pituitary gland of
      the spontaneously hypertensive rat.
AB  - The levels of dynorphin A-like immunoreactivity (Dyn A-LI) and dynorphin B-like
      immunoreactivity (Dyn B-LI) were determined in various regions of brain, spinal
      cord and pituitary gland in spontaneously hypertensive rats (SHRs) as compared
      with the normotensive Wistar-Kyoto rats (WKYs). SHRs had significantly lower
      levels of Dyn A-LI and Dyn B-LI in the neurointermediate pituitary lobe and in
      the hippocampus. Conversely, the levels of Dyn A-LI and Dyn B-LI were higher in
      the hypothalamus, striatum and periaqueductal gray of the SHRs.

PMID- 9185162
TI  - A brain-derived neurotrophic factor (BDNF) related system is involved in the
      maintenance of the polyinnervate Torpedo electric organ.
AB  - Target-derived molecules are essential for the maintenance of neuron survival. In
      the present work, we introduce the electric organ of Torpedo marmorata as a tool
      for the study of trophic interactions in a polyinervate system. This electric
      organ maintains a large number of cholinergic terminals on the postsynaptic cell
      surface. We have observed that a soluble extract derived from the electric organ
      induces the maturation of Xenopus oocytes injected with presynaptic plasma
      membranes (PSPM), indicating that a trophic system may exist. Moreover, we have
      detected a p75NGFR related protein in PSPM by Western blot analysis. These
      results suggest the presence of a neurotrophin-related system maintaining the
      polyinnervate electric organ. Furthermore, molecular experiments showed that the
      brain-derived neurotrophic factor (BDNF) is the neurotrophin operating in our
      model. Using degenerate oligonucleotides which comprise a conserved fragment of
      all neurotrophins, we have only amplified by polymerase chain reaction a BDNF
      fragment. In a similar way, we have amplified and cloned a fragment of the TrkB/C
      high affinity BDNF receptor. The fact that degenerate oligonucleotides only
      amplify BDNF allows us to conclude that the polyinnervation is maintained by this
      neurotrophin either alone or in combination with other trophic factors.

PMID- 9185163
TI  - Different response of cerebral and non-cerebral endothelial cells to cytotoxic
      hypoxia.
AB  - The present study investigated the effect of cytotoxic hypoxia on cerebral and
      non-cerebral endothelial cells. Hypoxia was induced by inhibiting the cellular
      respiratory chain with 1 mM sodium cyanide. Cerebral endothelial cells were
      damaged after 2 h of hypoxia as assessed by a decrease in cell viability by 25%
      and by a 2.7-fold higher lactate dehydrogenase release compared to controls.
      Additional glucose deprivation did not significantly exacerbate hypoxic injury.
      In addition, we found after 2 h of hypoxia an increase in the release of lactate
      of 1.02 and 0.42 mg/mg protein compared to 0.27 and 0.07 mg/mg protein in
      controls in the presence and absence of glucose, respectively. While the activity
      of ALP of cerebral endothelial cells was maintained at the control level, we
      found a significant decrease in the gamma-GT activity from 3.8 +/- 1.3 to 1.09 +/
      0.3 U/mg protein after 3 h of hypoxia in the presence as well as in the absence
      of glucose. The paracellular permeability of the cell monolayer decreased after 1
      h and returned to control level after 3 h of hypoxia in the presence of glucose.
      Non-cerebral endothelial cells remained 98% viable with no change in the release
      of lactate dehydrogenase and lactate after 2 h of hypoxia in the presence and
      absence of glucose. The activities of ALP and gamma-GT in non-cerebral
      endothelial cells were 10 and 3 times lower and remained unchanged during
      hypoxia. We conclude from our experiments that sodium cyanide is useful to study
      hypoxic injury and that cerebral endothelial cells are more sensitive than non
      cerebral endothelial cells to cytotoxic hypoxia.

PMID- 9185165
TI  - Intracellular Ca2+ signals induced by ATP and thapsigargin in glioma C6 cells.
      Calcium pools sensitive to inositol 1,4,5-trisphosphate and thapsigargin.
AB  - In glioma C6 cells, extracellular ATP generates inositol 1,4,5-trisphosphate
      (InsP3), indicating the presence of purinergic receptors coupled to
      phosphoinositide turnover. To identify the effect of ATP (acting via InsP3) and
      thapsigargin (acting without InsP3 production as a specific inhibitor of the
      endoplasmic reticulum Ca(2+)-ATPase) on intracellular Ca2+ pools we used video
      imaging of Fura-2 loaded into single, intact glioma C6 cells. It has been shown
      that ATP and thapsigargin initiate Ca2+ response consistent with the capacitative
      model of Ca2+ influx. When the cells were stimulated by increasing concentrations
      of ATP (1, 10, 50 and 100 microM) the graded, quantal Ca2+ response was observed.
      In the absence of extracellular Ca2+ thapsigargin and ionomycin-releasable Ca2+
      pools are overlapping, demonstrating that Ca2+ stores are located mainly in the
      endoplasmic reticulum. After maximal Ca2+ mobilization by ATP, thapsigargin
      causes further increase in cytosolic Ca2+ concentration, whereas emptying of
      thapsigargin-sensitive intracellular stores prevents any further Ca2+ release by
      ATP. Thus, the thapsigargin-sensitive intracellular pool of Ca2+ in glioma C6
      cells seems to be larger than that sensitive to InsP3. Two hypothesis to explain
      this result are proposed. One postulates a presence of two different Ca2+ pools,
      sensitive and insensitive to InsP3 and both discharged by thapsigargin, and the
      other, the same intracellular pool of Ca2+ completely emptying by thapsigargin
      and only partially by InsP3. These results may contribute to understanding the
      mechanism of Ca2+ signalling mediated by ATP, the most potent intracellular Ca2+
      mobilizing agonist in all types of glial cells.

PMID- 9185164
TI  - Characterization of a nuclear factor that enhances DNA binding activity of SSCRE
      BP/PUR alpha, a single-stranded DNA binding protein.
AB  - Pur alpha has been identified as a single-stranded DNA binding protein that
      specifically binds to the purine-rich strand present in the DNA replication
      initiation zone of the human c-myc gene. We have previously demonstrated that
      chronic morphine treatment decreases the DNA binding activity of ssCRE-BP (single
      stranded cyclic AMP response element-binding protein), which has been shown to be
      identical to pur alpha by cDNA cloning, and is abundant in the brain. In this
      report we identified an activator of ssCRE-BP/pur alpha in the brain and
      characterized it. Although purified ssCRE-BP/pur alpha or its GST-fusion protein
      exhibited very low DNA binding activities, they were markedly enhanced by
      including nuclear extract in the binding assay. The enhanced binding activity is
      trypsin-sensitive, heat-stable and has a molecular weight of approximately 66
      kDa. Casein could substitute for the activator and increased the DNA binding
      activity of ssCRE-BP/pur alpha by one order. A series of deletion mutants were
      prepared in order to determine the DNA binding and activator interacting domains,
      and both of them were found to reside in AA 50-215 of ssCRE-BP/pur alpha. These
      data suggest that the DNA binding activity of ssCRE-BP/pur alpha is augmented by
      a nuclear protein, which may modulate the ssCRE-BP/pur alpha activity to develop
      morphine dependence and tolerance.

PMID- 9185166
TI  - Analysis of molecular forms and pharmacological properties of
      acetylcholinesterase in several mosquito species.
AB  - Two acetylcholinesterases (AChE1 and AChE2) have recently been characterized in
      the common mosquito Culex pipiens. This situation appeared to be an exception
      among insects, where only one acetylcholinesterase gene had previously been
      repeatedly reported. In the present study, acetylcholinesterase was studied in
      five mosquito species: Aedes aegypti, Anopheles gambiae, Anopheles stephensi,
      Culiseta longeareolata and Culex hortensis, in order to test whether or not two
      different acetylcholinesterase enzymes could be detected as occurs in C. pipiens.
      Molecular forms and catalytic properties of the enzyme show that only one enzyme
      species was detected in the five species. This suggests that a duplication of a
      single locus Ace probably occurred recently in the phylogeny tree leading to C.
      pipiens, and produced two distinct acetylcholinesterases: AchE1 and AChE2.

PMID- 9185167
TI  - Modulation by both diphenyliodonium and diphenyleneiodonium of [3H]MK-801 binding
      to rat brain synaptic membranes.
AB  - Binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne
      (MK-801) was significantly inhibited by the addition of several different
      compounds related to generation of nitric oxide (NO) at 100 microM in rat brain
      synaptic membranes. These included sodium nitroprusside, diphenyliodonium (DI),
      diphenyleneiodonium (DPI) and methylene blue. However, neither S-nitroso-N
      acetylpenicillamine nor S-nitroso-L-glutathione inhibited binding at 100 microM.
      Both DI and DPI inhibited binding in a concentration-dependent manner at a
      concentration range of over 1 microM, while further addition of spermidine (SPD)
      significantly attenuated the potency of DPI to inhibit binding without affecting
      that of DI. In contrast, SPD induced significant potentiation of the ability of
      unlabelled MK-801 to displace [3H]MK-801 binding in a fashion sensitive to
      antagonism by the novel polyamine antagonist bis-(3-aminopropyl)nonanediamine.
      This novel polyamine antagonist also prevented the reversing effect of SPD on
      inhibition by DPI of [3H]MK-801 binding. Moreover, DPI competitively exacerbated
      the ability of SPD to potentiate [3H]MK-801 binding in the presence of both L
      glutamic acid and glycine at maximally effective concentrations. On the other
      hand, SPD was effective in reversing the inhibition by DPI in cerebellar, but not
      hippocampal, synaptic membranes. These results suggest that both DI and DPI may
      modulate synaptic responses mediated by the N-methyl-D-aspartate receptor through
      inhibition of opening processes of the ion channel in a manner irrespective of
      generation of NO radicals in particular situations. Possible involvement of the
      polyamine domain in the inhibition by DPI is also suggested.

PMID- 9185168
TI  - Characterization of a serotonin receptor in the cnidarian Renilla koellikeri: a
      radiobinding analysis.
AB  - Serotonin (5-HT) binding sites in membrane preparations from the sea pansy
      Renilla koellikeri were identified using [3H]5-HT as radioligand and unlabelled 5
      HT as displacer of specific binding. Saturation and kinetic studies revealed a
      mixed population of [3H]5-HT binding sites which as a whole displayed slow
      association kinetics, saturability, negligible dissociation and low affinity. The
      dopaminergic antagonist trifluoperazine specifically displaced the non
      dissociated binding sites, allowing the characterization of a homogenous
      population of saturable sites exhibiting faster association and full
      dissociation. Scatchard analysis of this population revealed a KD of 23-34 nM and
      binding site density (Bmax) of 8.5-20.6 pmol/mg protein depending on body region.
      The pharmacological profile of the dissociable [3H]5-HT binding sites could not
      be categorized with that of any of the existing vertebrate and invertebrate 5-HT
      receptor subtypes in the current nomenclature. Especially noteworthy was the
      absolute inability of LSD, a ligand of choice for all hitherto identified
      invertebrate 5-HT receptors, to compete for the binding sites in sea pansy
      membrane preparations. It is proposed that these binding sites represent an
      evolutionary forerunner of the primordial 5-HT receptor that diversified as
      multiple subtypes in higher invertebrates and vertebrates.

PMID- 9185169
TI  - Quantitative determination of glutamate turnover by 1H-observed, 13C-edited
      nuclear magnetic resonance spectroscopy in the cerebral cortex ex vivo:
      interrelationships with oxygen consumption.
AB  - The kinetics of glutamate 13C-4 label appearance from D-[1-13C]-glucose and 13C-4
      label disappearance from steady state following D-12C-glucose incubation were
      quantified with 1H-observed, 13C-edited nuclear magnetic resonance (NMR)
      spectroscopy in the superfused brain slices under largely varying oxygen
      consumption. Label incorporation to and from glutamate C-4 were fitted into mono-
      or bicompartmental models in order to determine the respective rate constants and
      to assess the presence of plausible multiple pools. At a steady-state oxygen
      consumption of approximately 4 mumol/min/g dry weight, glutamate labelling could
      be fitted into a biexponential equation, suggesting that there were two
      compartments with a large difference in their rates (respective rate constants of
      0.022 and 0.149) and pool sizes (relative contributions of 91.2 and 8.8%,
      respectively). Stimulation of oxygen consumption in the brain slice preparations
      with either 40 mM KCl by 59.5 +/- 10.3% or 5 microM carbonyl cyanide m
      fluorophenyl hydrazone by 61.4 +/- 8.4% increased glutamate C-4 labelling rate
      constants to 0.058 +/- 0.009 and 0.054 +/- 0.006, respectively. In the stimulated
      slice preparation, glutamate labelling could only be fitted into a
      monoexponential equation. 13C-4 label disappearance, independent of oxygen
      uptake, could also only be fitted into a monoexponential equation. There was a
      close match between the rate constants of label disappearance and appearance in
      non-stimulated and carbonyl cyanide m-fluorophenyl hydrazone-stimulated slices.
      In the presence of 40 mM KCl label disappearance did not, however, increase.
      These data show that glutamate C-4 turnover from exogenous D-[1-13C]-glucose can
      be used as an index of oxidative metabolism in situ under steady-state conditions
      as well as when oxygen metabolism is strongly stimulated. The results are
      discussed with respect to the use of NMR spectroscopy as a means of mapping brain
      oxidative metabolism.

PMID- 9185170
TI  - Light exposure stimulates the activity of ganglioside glycosyltransferases of
      retina ganglion cells.
AB  - In chicks submitted to light stimulation, the synthesis of gangliosides of the
      retina ganglion cell increases with respect to chicks maintained in the dark. In
      an attempt to elucidate if the activation of glycosyltransferases participates in
      the establishment of these light-dark differences detected in vivo, we examined
      the activity of a key ganglioside glycosyltransferase, the GalNAc-T (N
      acetylgalactosaminyltransferase) that converts GM3 to GM2, in the retina ganglion
      cells isolated from light and dark exposed chicks. We found that GalNAc-T and
      other glycosyltransferases are active in these ganglion cell preparations; the
      kinetic parameters for GalNAc-T were similar to those previously reported for
      chick retina. The other glycosyltransferase activities assayed were the
      galactosyltransferase (Gal-T2) that converts GM2 to GM1 and the N
      acetylneuraminyltransferase (Sialyl-T1) that converts lactosylceramide to GM3.
      The three glycosyltransferase activities were higher in the ganglion cell
      preparations obtained from chicks exposed to light compared to those maintained
      in the dark. For the GalNAc-T activity, the differences disappear when the cell
      preparations are sonicated or if the assays are carried out in the presence of
      detergents or if the end product of the reaction is added to the incubates. The
      results indicate that the activation of the glycosyltransferases is part of the
      phenomenon required for cells to achieve the precise rate of synthesis of
      gangliosides needed in vivo.

PMID- 9185171
TI  - Characterization of glutamate and [3H]D-aspartate outflow from various in vitro
      preparations of the rat hippocampus.
AB  - The characteristics of high-K+ and electrically evoked endogenous glutamate and
      [3H]D-aspartate release have been studied in multiple in vitro preparations of
      the rat hippocampus (transverse slices, granule cells cultures, synaptosomes and
      mossy fibre synaptosomes) under similar experimental conditions. High external K+
      concentrations evoked [3H]D-aspartate and endogenous glutamate overflow in a
      concentration-dependent manner in all preparations (except it was not possible to
      measure endogenous glutamate outflow from granule cells). This effect was
      tetrodotoxin-insensitive but partially calcium-dependent. In slices, field
      electrical stimulation evoked an overflow of endogenous glutamate, but not of
      [3H]D-aspartate, in a frequency-dependent manner. This effect was concentration
      dependently amplified by the glutamate uptake inhibitor L-trans-pyrrolidine-2,4
      dicarboxylic acid (t-PDC). The electrically evoked glutamate overflow in the
      presence of t-PDC was tetrodotoxin-sensitive and calcium-dependent. In primary
      dentate gyrus cell cultures, electrical stimulation evoked an overflow of [3H]D
      aspartate in a frequency-dependent manner, while endogenous glutamate outflow was
      not detectable. This effect could be inhibited by tetrodotoxin and by the N-type
      calcium channel blocker omega-conotoxin GVIA. Finally, the effect of adenosine
      has been studied in order to assess the pharmacological modulability of [3H]D
      aspartate and endogenous glutamate stimulation-induced overflow. Adenosine was
      found to inhibit 35 mM K(+)- and 20 Hz electrical stimulation-induced [3H]D
      aspartate and endogenous glutamate overflow. These effects were all prevented by
      the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). These data
      are in line with the hypothesis that reuptake plays a role in regulating
      glutamate release, and that [3H]D-aspartate represents a valid marker of
      endogenous glutamate under most (but not all) experimental conditions.

PMID- 9185172
TI  - The novel alpha 2-adrenoceptor agonist [3H]mivazerol binds to non-adrenergic
      binding sites in human striatum membranes that are distinct from imidazoline
      receptors.
AB  - The alpha 2 adrenergic agonist [3H]mivazerol labelled two populations of binding
      sites in membranes from the human striatum. Forty per cent of the sites labelled
      by 3 nM [3H]mivazerol corresponded to alpha 2 adrenergic receptors as they
      displayed a high affinity for (-)-adrenaline and for rauwolscine. The remaining
      binding was displaced by mivazerol with a pIC50 of 6.5 +/- 0.1. These sites
      displayed higher affinity for dexmedetomidine (pIC50 = 7.1 +/- 0.1), but much
      lower affinity for clonidine (pIC50 < 5.0) and for idazoxan (pIC50 = 5.1 +/-
      0.1). Mivazerol also showed low affinity for the [3H]clonidine-labelled I1
      imidazoline receptors and for the [3H]idazoxan-labelled I2 receptors (pIC50 = 5.1
      and 3.9, respectively). These results suggest that the non-adrenergic
      [3H]mivazerol binding sites are distinct from the imidazoline receptors in the
      human striatum.

PMID- 9185173
TI  - Quantification of dopamine D1 and D2 receptor mRNA levels associated with the
      development of behavioral sensitization in amphetamine treated rats.
AB  - We hypothesized that changes in expression of dopamine (DA) D1 and D2 receptor
      genes in caudate/putamen (CP) would correlate with the development of behavioral
      changes in amphetamine treated rats. In order to test this hypothesis, we
      measured DA D1 and D2 receptor mRNA in CP, as well as locomotor behavior, in
      individual rats following amphetamine treatment. D1 and D2 mRNA levels were
      similar in caudate/putamen of rats treated with acute amphetamine, chronic
      amphetamine or saline injection. We found no correlation between D1 or D2 mRNA
      levels in caudate/putamen and the behavioral response to either acute or chronic
      amphetamine. These results suggest that behavioral sensitization to amphetamine
      is not mediated through transcriptional regulation of D1 or D2 mRNA levels in
      caudate/putamen.

PMID- 9185174
TI  - Protein kinase C from bat brain: the enzyme from a hibernating mammal.
AB  - Protein kinase C (PKC) from brain of euthermic and hibernating bats (Myotis
      lucifugus) showed only one form as determined by hydroxylapatite chromatography,
      compared with three forms found in rat brain. Cross-reaction with antibodies to
      rabbit alpha, beta, and gamma isozymes showed that bat brain contained only
      PKC(gamma). During hibernation the activity of PKC in bat brain decreased to 63%
      of the euthermic value but the percentage that was membrane-associated did not
      change. Bat and rat brain PKC(gamma) were purified to homogeneity. Both enzymes
      phosphorylated all three of the substrates tested (FKKSFKL-NH2 peptide substrate,
      histone H1, protamine), the bat enzyme having significantly higher K(m) values
      than rat PKC for both peptide and histone. Both enzymes required phospholipids
      and Ca2+ for activation with rat brain PKC depending almost exclusively on
      phosphatidylserine. Bat PKC, however, made use of other phospholipids and showed
      relative activities of 100:81:33:42 for euthermic PKC and 100:91:45:35 for
      hibernator PKC with phosphatidylserine, phosphatidylinositol,
      phosphatidylcholine, and phosphatidylethanolamine (each at 50 microM),
      respectively. Activation of bat PKC by phosphatidylserine was temperature
      sensitive, being 3.5-fold at 4 degrees C (hibernating body temperature) compared
      with 14-18-fold at 33 degrees C (near euthermic body temperature). Arrhenius
      plots for bat brain PKC showed a sharp break below 10 degrees C; activation
      energies below this temperature were 11.5- and 5.2-fold greater than at higher
      temperatures for the enzyme from hibernating versus euthermic animals. By
      contrast, plots for the rat enzyme were linear over the range 0-42 degrees C. The
      data suggest that a sharp suppression of PKC activity by several mechanisms
      (reduced total activity, low temperature effects on activity and sensitivity to
      phospholipids) may be important to overall metabolic rate suppression during
      hibernation.

PMID- 9185175
TI  - Involvement of histidine 134 in the binding of alpha-bungarotoxin to the
      nicotinic acetylcholine receptor.
AB  - Peptides corresponding to the sequence alpha 124-147 of the Torpedo californica
      and Homo sapiens nicotinic cholinergic receptors were synthesized. The His
      residue at position 134 was ethoxyformylated or substituted by Ala. Effects of
      such modifications were studied by: (a) a toxin blot assay and (b) a competition
      assay between each peptide and the Discopyge Ischudii receptor for 125I alpha
      bungarotoxin, in solution. Apparent Kd values were 0.1 and 0.8 microM for Torpedo
      californica and Homo sapiens native peptides, respectively, and no binding was
      observed when the His residue was modified or substituted by Ala. ic50 values for
      the Torpedo californica and Homo sapiens fragments were 1.0 and 0.8 microM,
      respectively, and no significant displacement occurred when His 134 was
      ethoxyformylated or substituted by Ala. Hydroxylamine treatment restored 80-100%
      of their binding ability. Results strongly support the involvement of His 134 in
      the binding of alpha-bungarotoxin either to the Torpedo californica or the Homo
      sapiens receptor.

PMID- 9185176
TI  - External ophthalmoplegia in neuromuscular disorders: case report and review of
      the literature.
AB  - The extraocular muscles have a number of structural and functional properties
      that distinguish them from skeletal and cardiac muscle and these differences may
      be important in the differential involvement of extraocular muscles in various
      disease states. We present a case of congenital external ophthalmoplegia
      associated with non progressive generalised weakness. Skeletal muscle biopsy at 4
      years of age showed type 1 fibre predominance, variation in fibre size and
      increased interstitial fibrosis, suggestive of a primary myopathic process.
      During the investigation of this patient we reviewed the differential diagnosis
      of neuromuscular disorders with extraocular muscle involvement, and developed an
      algorithm to assist the clinician in investigation and diagnosis of external
      ophthalmoplegia. Our patient does not satisfy the diagnostic criteria of any
      previously described disorders and may thus represent a new syndrome.

PMID- 9185177
TI  - Variation of CTG-repeat number of the DMPK gene in muscle tissue.
AB  - Myotonic dystrophy (DM) is associated with an unstable expansion of CTG repeats
      located in the 3' untranslated region of a protein kinase-encoding gene (DMPK) on
      chromosome 19 (19q13.3). The CTG repeat number varies between 5 and 37 in
      lymphocytes of normal individuals, whereas DM patients may have expansions from
      50 to several thousand copies. Although the CTG expansions related to myotonic
      dystrophy (DM) are usually larger in muscle compared to peripheral blood, the
      variation in repeat number in non-dystrophic muscle is not known. In order to
      investigate if there is a variation, the CTG-repeat number was determined in
      percutaneous muscle biopsies obtained from 86 individuals without any muscle
      disorder or with a neuromuscular disorder without any clinical or
      histopathological signs of DM. The number of CTG repeats varied between 5 and 28,
      this being within the normal range reported for peripheral blood. A major sharp
      peak at n = 5 (27%) and a broader peak at n = 8-17 (56%) with peak values at n =
      12 and 14 (11 and 14%, respectively) were observed. Alleles with 19 or more
      repeats amounted to 17% with a small peak at n = 20 and 21 (6 and 4%,
      respectively). It is concluded that the normal variation of CTG-repeat number in
      skeletal muscle is within the range found in peripheral blood, although there is
      a slight shift in the overall frequency distribution towards alleles with CTG
      repeat numbers in the higher range.

PMID- 9185178
TI  - Mitochondrial tRNA(Cys) gene mutation (A5814G): a second family with
      mitochondrial encephalopathy.
AB  - We report an Italian family with maternally inherited encephalomyopathy including
      progressive external ophthalmoplegia, seizures, and neurophysiological evidence
      of brainstem dysfunction. Mitochondrial DNA analysis showed a heteroplasmic point
      mutation at position 5814 in the tRNA gene for cysteine (A5814G), previously
      reported in a 5-year-old girl of Portuguese origin. The mutation was very
      abundant (> 95%) in both muscle and blood from the proposita and was present in
      lower proportions (average 85 +/- 6%) in blood from three less severely affected
      maternal relatives. This observation confirms pathogenicity for the A5814G
      mutation.

PMID- 9185179
TI  - Congenital myopathy with excess of thin myofilaments.
AB  - Three unrelated young children are reported to have suffered since birth from
      muscle hypotonia and two of them from fatal respiratory insufficiency. Muscle
      tissues were found to contain large masses of thin myofilaments, immunologically
      identified as containing actin, but without further morphological features. These
      masses of thin filaments were found in different muscles at different occasions
      in the three children, suggesting a disease-specific morphological and possibly
      nosological feature all of them justifying classification as congenital myopathy
      with excess of actin or actin myopathy. The lesions were dissimilar to hyaline
      bodies in that the latter consist of granular material which is faintly positive
      for ATPase activity whereas the masses of thin filaments are devoid of ATPase
      activity. Two of our three patients also had intranuclear rods with virtually no
      sarcoplasmic rods suggesting the term of this congenital myopathy as actin
      myopathy with intranuclear rods.

PMID- 9185180
TI  - Variable clinical phenotype in merosin-deficient congenital muscular dystrophy
      associated with differential immunolabelling of two fragments of the laminin
      alpha 2 chain.
AB  - Approximately half the cases of classical congenital muscular dystrophy (CMD)
      have a pronounced deficiency or absence of the laminin alpha 2 chain of laminin-2
      (merosin). This is caused by mutations in the LAMA2 gene that codes for laminin
      alpha 2, and all informative cases so far studied show linkage to the appropriate
      region on chromosome 6q. Most CMD patients with a deficiency of laminin alpha 2
      have a severe phenotype that involves skeletal muscle, and the central and
      peripheral nervous system. We have identified four cases that have minimal
      reduction of laminin alpha 2 using a commercial antibody that only recognises a C
      terminal 80 kDa fragment, but show a pronounced reduction using an antibody to
      the 300 kDa fragment. Haplotype analysis is compatible with linkage to the LAMA2
      locus in three informative families, whilst the fourth family was not
      informative. Two of the affected children are ambulant and have a mild phenotype.
      The third case is unusual in having severe muscle weakness but does not show the
      white matter changes on magnetic resonance imaging of the brain that is usually
      seen in merosin-deficient cases of CMD; the fourth case has a severe phenotype,
      typical of merosin-deficient patients but shows good immunolabelling of the 80
      kDa fragment of laminin alpha 2, corresponding to the C-terminal region. Our data
      show that there is a broad spectrum of phenotype and protein expression
      associated with a primary deficiency in laminin alpha 2, and that a wider range
      of clinical cases need to be screened for a deficiency of merosin. It is also
      important to study the expression of laminin alpha 2 with more than one antibody.

PMID- 9185181
TI  - Prenatal diagnosis in merosin-deficient congenital muscular dystrophy.
AB  - Prenatal diagnosis was carried out in five merosin-deficient congenital muscular
      dystrophy (CMD) families. We studied both laminin-alpha 2 chain expression in
      trophoblast using immunocytochemistry and linkage analysis to the LAMA2 locus. In
      four families there was good agreement between the immunocytochemistry and
      linkage analysis results: in one case the trophoblast was negative for LAMA2
      expression and haplotype analysis suggested the foetus was affected; in the other
      three cases the laminin-alpha 2 chain expression was normal and foetuses were
      found to be carriers. In the remaining family, a case of partial laminin-alpha 2
      chain expression, the immunostaining of the trophoblast was weaker compared to
      the control. Linkage analysis, however, could not be performed because of
      maternal DNA contamination. After termination of pregnancy, the foetal muscle was
      studied and suggested weak laminin-alpha 2 chain expression. The haplotype
      analysis however showed that the foetus was probably a carrier, unless a double
      recombinant event had occurred. We conclude that a combination of
      immunocytochemistry and linkage analysis can be used for the prenatal diagnosis
      of merosin deficient CMD. The results are easy to interpret in families with
      total absence of the protein, while caution is required when dealing with
      families where partial expression occurs.

PMID- 9185182
TI  - Genetics of laminin alpha 2 chain (or merosin) deficient congenital muscular
      dystrophy: from identification of mutations to prenatal diagnosis.
AB  - Congenital muscular dystrophies (CMD) are a clinically and genetically
      heterogeneous group of muscle disorders, with autosomal recessive inheritance.
      Absence of the laminin alpha 2 chain in the skeletal muscle of patients with
      classical CMD has permitted the identification of a subgroup, referred to as
      'merosin-deficient CMD or laminin alpha 2 chain deficient CMD'. We first
      identified a nonsense and a splice site mutation in laminin alpha 2 gene (LAMA2)
      (Glu1241 stop, 4573-2A-->T). We report here new mutations: nonsense mutations
      (Glu210stop, Trp2316stop) and 1- and 2-bp deletions (2418 delta C, 6968 delta
      TA), which result in truncation of the protein either in the short arm domains or
      in the C terminal globular domain and complete merosin deficiency. Another
      subgroup, referred to as 'partially-deficient in laminin alpha 2 chain' has been
      identified recently, and a LAMA2 missense mutation (Cys996Arg) has been shown to
      cause this partial deficiency. The laminin alpha 2 chain, together with the beta
      1 or beta 2 and gamma 1 chains forms either laminin-2 (alpha 2-beta 1-gamma 1) or
      laminin-4 (alpha 2-beta 2-gamma 1). The LAMA2 mutations induce the formation of
      abnormal laminins which probably dramatically disturb the assembly and stability
      of the laminin network, one of the major components of the extracellular matrix
      in skeletal muscle. We report also the first prenatal diagnosis performed by
      direct mutation analysis.

PMID- 9185183
TI  - Merosin positive congenital muscular dystrophy with mental deficiency, epilepsy
      and MRI changes in the cerebral white matter.
AB  - A girl born from consanguineous Turkish parents had marked hypotonia from birth
      and delayed milestones. She was able to stand unaided by 3 years of age with then
      progressive worsening of motor abilities. She had a severe non-progressive mental
      deficiency. Epilepsy occurred by 6 years of age. Ophthalmological investigation
      was normal. A marked white matter high signal was seen on magnetic resonance
      imaging without cortical dysplasia. Dystrophic changes were seen on muscle
      biopsy. Two brothers had had a similar history with early death. Muscular
      immunocytochemical studies showed a normal staining for dystrophin and all
      dystrophin related glycoproteins (including 43 and 50 DAG). Merosin staining was
      normal. This case differs from Fukuyama's congenital dystrophy, from merosin
      negative congenital muscular dystrophy, or from other congenital muscular
      dystrophy with CNS dysfunction. It underlines the heterogeneity of congenital
      muscular dystrophy and the non-specific aspect of white matter changes on neuro
      imaging.

PMID- 9185184
TI  - Electron microscopic examination of basal lamina in Fukuyama congenital muscular
      dystrophy.
AB  - By light microscopy we previously obtained immunocytochemical evidence for basal
      lamina (BL) abnormality of skeletal muscle in Fukuyama congenital muscular
      dystrophy (FCMD). To further elucidate the pathological involvement of the BL in
      FCMD, we examined by electron microscopy the skeletal muscle in 12 cases of FCMD,
      nine cases of age-matched neuromuscular diseases unrelated to FCMD, and a case of
      merosin-negative CMD (MCMD). We found that the BL of skeletal muscle fibres in
      all patients with FCMD and the MCMD patient had a thin, deranged and often
      disrupted appearance. These features were more prominent in large calibre (> 15
      microns) fibres than in small calibre (approximately 8 microns) fibres.
      Replication of the BL was not observed in 11 of the 12 FCMD patients. Although
      the BL over the intact plasma membrane had occasional gaps, the plasma membrane
      under the disrupted BL was normal in some case. Our results indicate the presence
      of fragile BL which may precede plasma membrane damage in FCMD skeletal muscle.

PMID- 9185186
TI  - Spinal muscular atrophy--clinical and genetic correlations.
AB  - A clinical and molecular genetic study of nearly 500 patients with proximal
      spinal muscular atrophy (SMA) was undertaken. On the basis of defined achieved
      milestones, survival probabilities in type I (never able to sit), type II (able
      to sit but not to walk) and the probability of being ambulatory in type III
      (achieved ability to walk) SMA for a total of 445 patients with SMA are given.
      Specific deletions of the survival motor neuron (SMN) gene were found in 96% type
      I, 94% type II and 82% type III in a total of 191 patients, while four SMA type
      IV patients with an age of onset beyond 30 years were not deleted. The SMN gene
      obviously plays an important role in the pathogenesis of SMA but there is
      evidence that the SMN gene is not the SMA gene itself. The demonstration of SMN
      deletions in healthy siblings of affected persons, the high intrafamilial
      similarity of the clinical course on the background of a broad clinical spectrum
      of proximal SMA and the demonstration of different mutations causing different
      clinical manifestations in single pedigrees indicate that additional genetic
      factors might be relevant. Linkage studies, as well as the analysis of the SMN
      gene, recognised that SMA variants (with severe arthogryposis or cerebellar or
      diaphragmatic involvement) are not linked to chromosome 5q markers.

PMID- 9185185
TI  - Gene conversion at the SMN locus in autosomal recessive spinal muscular atrophy
      does not predict a mild phenotype.
AB  - Autosomal recessive proximal spinal muscular atrophy (SMA) is a disease of motor
      neuron death and a common cause of morbidity in childhood. It has been mapped to
      5q13 and shown to be associated with deletions in a gene which has been called
      the survival motor neuron (SMN) gene. SMN exists in two copies in 5q13 and
      deletions in exon 7 and 8 of the telomeric copy (SMNtel) occur in over 90% of
      patients regardless of disease severity. In contrast, deletion of exon 7 and 8 of
      the centromeric copy of SMN is present in 3-5% of the normal population. In a
      minority of patients, exon 7 but not exon 8 of SMNtel appears deleted. The
      purpose of this study was to analyse this latter type of deletion in more detail.
      In all patients where there was absence of PCR amplification of exon 7 but not
      exon 8 of SMNtel this was found to be due to replacement with the homologous copy
      of SMNcen by a possible gene conversion event. This type of mutation occurred in
      all grades of severity of SMA.

PMID- 9185187
TI  - Neuromuscular disorders: gene location.

PMID- 9185188
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9185189
TI  - Functional eyelid surgery.

PMID- 9185190
TI  - Preventing ptosis after botulinum treatment.
AB  - In a series of 33 blepharospasm patients who had the side effect of ptosis
      following therapeutic botulinum toxin type A (Botox: Allergan, Inc., Irvine, CA,
      U.S.A.) injection, we administered 41 injections of human botulinum immune
      globulin (IG) following injections of the toxin to test the dosage and timing of
      IG injection and its effectiveness in limiting or avoiding ptosis. An IG dose of
      3.2 x 10(-3) international units (IU) per unit of Botox was effective in blocking
      toxin effect when injected into the same tissue site within 4 hours. An IG dose
      of 1.6 x 10(-2) to 3.2 x 10(-2) into the levator of the eye having more frequent
      ptosis in 19 patients reduced the incidence of ptosis to 11%. The fellow
      (control) eye had a ptosis incidence of 37%. No orbital hemorrhage or other
      adverse effect occurred from the IG or its injection.

PMID- 9185191
TI  - Septal-myocutaneous flap technique for lower lid blepharoplasty.
AB  - Lower lid blepharoplasty can present a significant challenge to the facial
      plastic surgeon. Routine findings of periorbital fat herniation and
      dermatochalasia of the lower lid are often associated with the presence of more
      occult findings, e.g., tarsoligamentous laxity and ectropion. Traditional
      surgical approaches to the aging lower eyelid utilize the skin flap, the skin
      muscle flap, and the transconjunctival technique. The limitation of any one of
      these procedures alone is that of not addressing the multiple problems of the
      aging eyelid; this may lead to common postoperative problems of lower lid
      blepharoplasty, including lid retraction, lagopthalmos, scleral show, rounding of
      the lateral canthus, and ectropion. We present an integrated surgical solution to
      the functional and anatomical defects of both the anterior and posterior
      lamellae, and, when indicated, lateral canthal support. The procedure
      incorporates a small lateral subciliary and lateral canthal incision with a
      myocutaneous advancement flap developed in a plane deep to the orbital septum,
      combined with transconjunctival blepharoplasty for removal of herniated orbital
      fat. It allows for simultaneous management of the multiple defects of the aging
      lower eyelid and complete restoration of the relevant anatomy, while avoiding the
      common pitfalls of lower lid blepharoplasty. We present our experience of 64
      patients who underwent bilateral combined septal-myocutaneous advancement flap
      and transconjunctival blepharoplasty. Indications and postoperative results are
      reviewed. No complications, including scleral show or ectropion, have been noted
      over the 4-year postoperative period.

PMID- 9185192
TI  - Tarsoconjunctival flap supplementation: an approach to the reconstruction of
      large lower eyelid defects.
AB  - In the presence of a full-thickness lower eyelid defect too large for
      reconstruction with a tarsoconjunctival flap alone, the posterior lamella is
      often reconstructed with a free graft of nasal septal cartilage and mucosa, ear
      cartilage, or hard palate mucosa. In this series, an alternative approach was
      taken: a tarsoconjunctival flap of maximum horizontal dimension was created to
      reconstruct the majority of the posterior lamella defect. A second reconstruction
      technique, such as a periosteal flap or a Tenzel semicircular flap, was then used
      to supplement the tarsoconjunctival flap and reconstruct the remainder of the
      posterior lamella defect. Tarsoconjunctival flap supplementation yielded
      favorable results in eight patients and is advocated for the reconstruction of
      large posterior lamella defects too large for reconstruction with a
      tarsoconjunctival flap alone.

PMID- 9185193
TI  - Floppy eyelid syndrome and obstructive sleep apnea.
AB  - Floppy eyelid syndrome (FES) usually affects middle-aged obese men, presenting as
      a unilateral or bilateral chronic papillary conjunctivitis. The upper eyelid is
      lax, floppy, and easily everted. The laterality corresponds to the side the
      patient sleeps on. An association with obstructive sleep apnea (OSA) has been
      suggested. A personal series of 17 new cases is presented, and 79 previously
      reported cases are reviewed to give a detailed description of the syndrome. In
      addition to the classical presentation, patients may present with upper lid
      ptosis, lash ptosis or trichiasis, lower lid ectropion or rarely entropion, or
      corneal complications. Eight patients with FES were investigated for OSA. Twenty
      other patients with known OSA were examined for FES and other possibly associated
      ocular features. All eight patients referred for sleep studies were found to have
      OSA. One of the 20 patients with known OSA was found to have FES, and two had
      features of early asymptomatic FES. One patient with FES and OSA had normal
      tension glaucoma. Patients with FES should be considered for sleep studies
      because of the known morbidity of OSA. Simple screening of patients with OSA may
      detect FES and avoid late corneal complications that can compromise vision.

PMID- 9185194
TI  - The effect of maturation on the ability to stimulate orbital growth using tissue
      expanders in the anophthalmic cat orbit.
AB  - Tissue expanders were used to stimulate orbital growth at different stages of
      maturity in the immature anophthalmic cat orbit. Twelve cats had the right globe
      enucleated at 2 weeks of age and tissue expanders implanted in the orbit. The
      cats were randomized into four groups (A, B, C, and D). The tissue expanders
      remained in the nonexpanded state for a preassigned length of time. Orbital
      volume was determined on each cat using computed tomography (CT) immediately
      prior to expansion of the implant. Expansion began at age 10 weeks for group A,
      15 weeks for group B, and 25 weeks for group C and involved 0.7 cc injections of
      saline at 2-week intervals until a final volume of 4.5 cc was obtained. Group D
      remained as a nonexpansion control group. Four to 5 weeks after expansion was
      completed, a second orbital volume CT was obtained on each animal and compared
      with the pre-expansion CT. The right orbits of group A, had pre-expansion (week
      10) orbital hypoplasia with a volume 26.2% smaller than the left control orbits.
      Postexpansion (week 25), the right orbital hypoplasia had decreased to a volume
      10.3% less than the left control orbits. The right orbits of group B had pre
      expansion (week 15) orbital hypoplasia with a volume 35.6% smaller than the left
      control orbits. Postexpansion (week 31), the right orbital hypoplasia had
      decreased to a volume 25.9% less than the left control orbits. The right orbits
      of group C had a preexpansion (week 25) orbital hypoplasia with a volume 39.8%
      smaller than the left control orbits. Postexpansion (week 41), the right orbital
      hypoplasia had decreased to a volume 29.3% less than the left control orbit.
      Tissue expanders, expanded in the hypoplastic immature cat orbit stimulated
      orbital growth and reversed orbital bony hypoplasia to varying degrees. The
      amount of growth stimulated was inversely proportional to the age at which
      expansion began. Orbital growth, stimulated by tissue expander expansion, was
      also demonstrated after the normal age of cat orbit maturation (weeks 28-30).

PMID- 9185195
TI  - Predictability of magnetic resonance imaging in differentiation of orbital
      lymphoma from orbital inflammatory syndrome.
AB  - Twenty-two patients with clinical presentations of either orbital lymphoma or
      orbital inflammatory syndrome (OIS) involving 25 orbits were examined by magnetic
      resonance imaging (MRI) before biopsy. To determine whether MRI adds specificity
      to radiographic diagnosis, the MRI signal characteristics of all tumors were
      examined. Attention was focused on the signal intensity of each tumor on T1- and
      T2-weighted images. In nine of 12 (75%) orbital lymphomas, the tumors appeared
      hyperintense to fat on T2-weighted images and became brighter relative to their
      appearance on T1-weighted images. In 11 of 13 (85%) orbital infiltrates with OIS,
      the tumors appeared isointense to fat on T2-weighted images and became slightly
      darker or unchanged relative to their appearance on T1-weighted images. Tumor
      density and homogeneity were fairly similar in all 25 lesions and were therefore
      not useful for further differentiation. Similarly, the presence of moderate
      enhancement with gadopentetate dimeglumine was seen in all but one tumor, and it
      was therefore not useful for further differentiation.

PMID- 9185196
TI  - Pseudomonas dacryoadenitis secondary to a lacrimal gland ductule stone.
AB  - Infectious dacryoadenitis is a rare condition. A case of Pseudomonas
      dacryoadenitis has not been reported previously. We treated a patient with
      Pseudomonas dacryoadenitis secondary to obstruction from a lacrimal gland ductule
      stone. Histologically, the calculus contained hairs.

PMID- 9185197
TI  - Congenital symblepharon (abortive cryptophthalmos) associated with
      meningoencephalocele.
AB  - An 18-year-old male patient was first seen with right congenital symblepharon
      (abortive cryptophthalmos) and right frontal meningoencephalocele. There were no
      other affected members in the pedigree. Computed tomograms revealed that the
      right orbital roof was absent. Apart from a right harelip on the affected side,
      there were no other systemic abnormalities. The eye had light perception only.
      The upper eyelid connected with the globe and the cornea was totally opaque.
      Echographic studies showed that the eye was improperly developed.
      Electroencephalography detected slow-wave activity over the right frontoparietal
      region.

PMID- 9185199
TI  - Theoretical considerations in the placement of hydroxyapatite orbital implants.

PMID- 9185198
TI  - Congenital orbital teratoma: a clinicopathologic case report.
AB  - A 5-day-old infant boy was noted to have severe left proptosis at birth. The left
      eye protruded superotemporally through the palpebral fissure and had exposure
      keratopathy. There was frank left afferent pupillary defect. Computerized
      tomography (CT) showed a left orbital soft tissue mass with foci of
      calcification. Magnetic resonance imaging (MRI) studies revealed a left orbital
      mass with solid and cystic portions without intracranial extension. As the eye
      was considered to be nonsalvagable, a lid-sparing type, modified exenteration was
      performed. Histopathologic examination demonstrated various mature tissues of all
      three embryonic germinal cell lines. This case represents one of the rare
      examples of true congenital orbital teratoma, which is an uncommon cause of
      hideous proptosis in the neonate. MRI may prove useful in differentiating this
      tumor from more common conditions.

PMID- 9185200
TI  - ICRF-187 as a cardioprotectant in children treated with anthracyclines.

PMID- 9185201
TI  - Genotypes and phenotypes of beta-thalassemia in Mediterranean populations.

PMID- 9185202
TI  - Understanding the psychosocial late effects of childhood cancer therapy.

PMID- 9185203
TI  - Pediatric oncology and hematology in Manchester, England.
AB  - The Manchester pediatric oncology unit is the third largest unit in the United
      Kingdom, with approximately 120 new referred cases per annum (10% of the U.K.
      total). Research activities include a gene therapy program, peripheral blood stem
      cell studies, the genetic epidemiology of childhood cancer, late-effects research
      (growth, body composition, pulmonary, quality of life), psychosocial studies, and
      clinical trial organization. Both the clinical oncology service and research
      activities involve close team coordination and collaboration with scientists both
      within and outside Manchester. A comprehensive pediatric hematology service is
      provided. The unit contains the second largest children's hemophilia service in
      the United Kingdom, serving 200 patients with congenital blood disorders. Twenty
      five bone marrow transplants are performed each year (allogeneic, unrelated
      donor, autologous, and peripheral stem cell) for malignant and nonmalignant
      disorders. These activities are closely related to local, national, and
      international research groups.

PMID- 9185204
TI  - Academic pediatrics in the Emma Children's Hospital, Academic Medical Center in
      Amsterdam (The Netherlands).
AB  - In 1988 the Emma Children's Hospital and the department of pediatrics of the
      Academic Medical Center in Amsterdam (The Netherlands) merged. With the
      integration of the Emma Children's Hospital and the academic pediatric
      department, an academic children's hospital (ECH/ AMC) was established with all
      pediatric subspecialties including oncology, pediatric hematology/ hemostasis,
      and immunology. The research is organized in special research institutes.
      Oncology patients are referred from all over The Netherlands (and consist of one
      third of the total Dutch pediatric oncology patients) and from many other
      countries. Considerable effort is given to the care of patients with hemophilia
      and congenital clotting disorders. One of the special fields in immunology is the
      care for children infected with human immunodeficiency virus (HIV). The Emma
      Children's Hospital AMC participates in national and international programs for
      human immunodeficiency virus and AIDS research and immunological diseases,
      especially chronic granulomatous disease, in which an internationally appreciated
      know-how has been built up.

PMID- 9185205
TI  - Outpatient antimicrobial protocol for febrile neutropenia: a nonrandomized
      prospective trial using ceftriaxone, amikacin, and oral adjuvant agents.
AB  - Broad-spectrum antimicrobial therapy has revolutionized the management of febrile
      neutropenia (FN) in cancer patients. In vogue is an effective therapy an an
      outpatient basis. One thousand three hundred episodes of FN observed in 70
      pediatric solid tumors (STs) and 65 cases of hematomalignancy (HM) at a median
      age of 5.5 years were treated with a protocol using once-a-day injectable
      ceftriaxone plus amikacin and other oral adjuvant antimicrobial agents. The mean
      duration of FN in the ST group was 4.0 +/- 1.2 days and in the HM group was 5.0
      +/- 2.5 days. The mean duration of antimicrobial cover in the ST group was 5.0 +/
      1.75 days and in the HM group was 6.0 +/- 1.5 days. The overall recrudescence
      rate was 6% and the mean duration to recrudescence was 4 +/- 1.5 days (range 3-6
      days). The objectives of this protocol were cost reduction and utilization of the
      available inpatient resources optimally by reducing the pressures of
      hospitalization for febrile neutropenia. We concluded that a selected group of
      patients with FN can be effectively managed with this regimen on an outpatient
      basis.

PMID- 9185206
TI  - Use of ICRF-187 for prevention of anthracycline cardiotoxicity in children:
      preliminary results.
AB  - The objective of this study is to assess the efficacy of ICRF-187 as a protective
      agent against anthracycline cardiotoxicity. Cardiac function was evaluated by
      echocardiography before and after each cycle of anthracycline chemotherapy
      associated with ICRF-187 and compared with that of a second group receiving
      anthracycline chemotherapy without ICRF-187. The patients were a group of 15
      consecutive children affected with various types of solid tumors who were treated
      with either doxorubicin-daunomycin or epirubicin (average doses 340 and 280
      mg/m2, respectively), and treatment was associated with ICRF-187. A second group
      of 15 consecutive children affected with different malignancies were
      simultaneously treated with either doxorubicin-daunomycin or epirubicin (average
      doses 309 and 270 mg/m2, respectively), but without ICRF-187 association. None of
      the patients treated with anthracyclines and ICRF-187 association showed
      abnormalities on echocardiographic examination. In the second group of patients
      treated with anthracyclines but without ICRF-187 association, we observed a
      decrease in the left ventricular ejection fraction to < 55% and a decrease in the
      left ventricular fractional shortening to < 28% in two patients (13.3%). One of
      these (6.6%) showed a dilatative cardiomyopathy. Both groups of patients were
      treated with low doses of anthracyclines. Although this study was not randomized,
      in patients without ICRF-87 cardioprotection, there was a trend for a worse
      evolution with one case of clinical cardiomyopathy as well as subclinical cardiac
      abnormalities.

PMID- 9185207
TI  - Physical and psychosocial outcome for young adults with treated malignancy.
AB  - We reexamined the physical, neurological, neuropsychological, social, and
      psychiatric circumstances of a group of 27 (10 females, 17 males) patients at the
      ages of 16-26 years who had survived a malignant disease during childhood. Twenty
      survivors had had leukemia and the rest different solid tumors. Only a third
      (31%) of the subjects were considered to be without any clinically significant
      physical health problems or functional symptoms, musculoskeletal and
      endocrinological disorders being the most common. In the neuropsychological test
      panel including verbal and performance IQ the survivors had significantly lower
      scores. Early onset of the disease and receiving radiotherapy correlated with
      impaired test results most significantly, especially on memory functions. One in
      five of the survivors reported having suffered from reading and writing problems
      that interfered with success in school and the subjects of the study group had
      progressed to high school less often than control subjects. The social indices
      indicated delayed development of sexuality and separation from parents. Overt
      mental problems appearing at a one-off interview were the same as in the control
      group. In conclusion, up to two thirds of the childhood cancer survivors as young
      adults still have physical or neuropsychological health problems and half showed
      delayed psychosexual maturation. This magnitude of various disorders indicates a
      long-term but individually oriented follow-up of this small group with the
      opportunity of physical, social, or psychological management of their main
      problem.

PMID- 9185208
TI  - Recognition of central nervous system metastases in children with metastatic
      primary extracranial neuroblastoma.
AB  - In children with primary extracranial neuroblastoma (NB), intrinsic central
      nervous system (CNS) metastases (brain parenchyma or leptomeninges) are thought
      to occur rarely. This study was done to evaluate our anecdotal experience, which
      suggested that CNS involvement is becoming more frequent. Reports of computed
      tomographic (CT) and magnetic resonance (MR) imaging scans, biopsies,
      cerebrospinal fluid (CSF) cytologies, and autopsies were reviewed for children
      with stage IV NB diagnosed in 1978-1993 and followed at the Children's Hospital
      of Pittsburgh. Of 43 children over the age of 1 year, CNS metastases were
      documented in 7 (16.2%). Six patients developed signs or symptoms best explained
      by the presence of CNS tumor and had radiographic and/or histologic evidence of
      parenchymal disease (cortical masses on CT and MR, n = 3; suprasellar mass on CT,
      n = 1; diffuse leptomeningeal carcinomatosis by MR and/or autopsy, n = 2). CSF
      cytologies were positive in the one patient so tested. An additional asymptomatic
      patient had extensive CNS involvement at autopsy. In two of these children, the
      CNS was the first or only site of recurrent disease. It is concluded that
      intrinsic CNS disease is not uncommon in children with NB over the age of 1 year
      and there has been a trend toward its increasing recognition in recent years.
      Whether this is a function of wider use of diagnostic tools or a true change in
      natural history over time with increased intensity of chemotherapy is not clear.
      A study that prospectively monitors children with advanced neuroblastoma,
      radiographically and with CSF cytologies (prior to treatment and at 6-monthly
      intervals), is under way and should help to better define the natural history in
      the context of current therapies.

PMID- 9185209
TI  - Imaging of pediatric head and neck rhabdomyosarcomas with emphasis on magnetic
      resonance imaging and a review of the literature.
AB  - We present the magnetic resonance imaging (MRI), computed tomography (CT) and
      ultrasound appearances of three cases of pediatric head and neck
      rhabdomyosarcomas, involving the orbit, parameningeal region (nasopharynx and
      nasal sinus), and trapezius muscle anatomically. The histopathological subtypes
      included two embryonal and one alveolar. MRI is a superior imaging technique with
      its high contrast resolution of soft tissue tumors and multiplanar noninvasive
      capability. The literature on CT and MRI appearances of head and neck
      rhabdomyosarcomas is reviewed.

PMID- 9185210
TI  - Vanilmandelic acid and homovanillic acid levels in patients with neural crest
      tumor: 24-hour urine collection versus random sample.
AB  - Neuroblastoma is the most common solid tumor in childhood and is the most
      frequent neural crest tumor (NCT). More than 90% of the patients excrete high
      levels of vanilmandelic acid (VMA) and homovanillic acid (HVA) in the urine.
      Original biochemical methods for measuring these two metabolites of
      catecholamines employed a collection of urine for 24 hours to avoid errors
      related to circadian cycle variations. More recently, attempts have been made to
      replace the 24-hour collections by random samples (RSs). This has practical
      advantages particularly for young children. The objective of this study is to
      assess whether urinary VMA related to urinary creatinine levels can be determined
      reliably by the method of Pisano et al. from RSs in patients with NCT. The
      determination of the consumption of VMA in urine stored for prolonged periods of
      time was also studied. We found a good correlation between the values of
      metabolites of catecholamines in RSs compared with 24-hour urine collections.
      There was consumption of VMA in urine samples after storage. We conclude that
      determination of VMA in RSs of urine by Pisano's method may identify NCT
      production of catecholamines and that the consumption of these catecholamines is
      an important factor to consider in the interpretation of values obtained with
      stored urine specimens.

PMID- 9185211
TI  - Pediatric tumors in north west Pakistan and Afghan refugees.
AB  - All patients referred to the Institute of Radiotherapy and Nuclear Medicine in
      Peshawar (IRNUM) during 1990 to 1994 were analyzed. There were 1655 children with
      biopsy-proven cancers; 1290 were from the North West Frontier Province (NWFP),
      and the remaining 365 were Afghan refugees. Male children from the NWFP were 67%
      and females were 33%. Among Afghan children, 69% were males and 31% were females.
      Patients whose histopathologies were doubtful or not available were excluded from
      the study. The most common tumors in children in the NWFP were lymphoid leukemia,
      lymphoma, myeloid leukemia, Wilms tumor, tumors of the central nervous system
      (CNS), soft tissue sarcoma, bone tumors, retinoblastoma, neuroblastoma, and
      testicular tumors. Among Afghan children the most common cancers were lymphoma,
      lymphoid leukemia, myeloid leukemia, Wilms tumor, retinoblastoma, tumors of soft
      tissue, bone tumors, CNS tumors, testicular tumors, and neuroblastoma.

PMID- 9185212
TI  - Late-onset hemorrhagic cystitis following bone marrow transplantation: a case
      report.
AB  - A 7-year-old child developed BK virus-induced hemorrhagic cystitis on day 16
      after an allogeneic bone marrow transplant. Contrary to previous reports,
      intravesical instillation of prostaglandin E2 was associated with considerable
      discomfort and failed to alleviate symptoms. Supportive treatment thereafter
      consisted of adequate hydration until the spontaneous resolution of symptoms on
      day 52.

PMID- 9185213
TI  - rhG-CSF in severe chronic neutropenia: successful intermittent treatment in three
      infants.
AB  - We report three cases of infants affected by severe chronic neutropenia (SCN).
      All the patients were treated with recombinant human granulocyte colony
      stimulating factor (rhG-CSF) to avoid or reduce recurrent fevers and severe
      infections. In order to obtain better compliance and reduce the costs of long
      term therapy while achieving the same effectiveness of therapy, we decided to
      evaluate intermittent treatment in patients with SCN. With a single dose of 3-10
      micrograms/kg/d subcutaneously every 3-7 days, the patient attained an absolute
      neutrophil count (ANC) of 0.5-1.5 x 10(9)/L, a reduction of infections, and no
      notable side effects.

PMID- 9185214
TI  - Immunophenotype and severity of marrow failure at diagnosis of lymphoblastic
      leukemia.

PMID- 9185215
TI  - Termination of transfusion dependence in beta-thalassemia: two-year experience
      with recombinant human erythropoietin.

PMID- 9185216
TI  - Prolactinemia in sickle cell disease.

PMID- 9185217
TI  - Enteropathies associated with protracted diarrhea of infancy: clinicopathological
      features, cellular and molecular mechanisms.

PMID- 9185218
TI  - "Polyphenotypic" tumors in the central nervous system: problems in nosology and
      classification.
AB  - In recent years, there is increasing recognition of polyphenotypic high-grade
      malignancies in the non-central nervous system (CNS) tumor literature. Some of
      these tumors have been regarded as variants of primitive neuroectodermal tumor
      (PNET) or as extrarenal malignant rhabdoid tumors (MRTs). This report concerns
      two posterior fossa neoplasms, both of which displayed a "polyphenotypic"
      expression of neural, epithelial, myogenic, and glial markers, including
      synaptophysin, neurofilament, vimentin, glial fibrillary acidic protein, S-100,
      neuron-specific enolase, desmin, S antigen, MIC2, cytokeratin, epithelial
      membrane antigen, and carcinoembryonic antigen. One tumor showed complex
      intercellular junctions, cytoplasmic intermediate filaments, well-developed rough
      and smooth endoplasmic reticulum and Golgi apparatus, cilia, and neurosecretory
      granules. The other neoplasm showed pools of glycogen, desmosomes, and
      tonofilaments. The histological and ultrastructural appearances were inconsistent
      with glioma, PNET, meningioma, ependymoma, choroid plexus carcinoma, sarcoma,
      germ cell tumor, and other tumors in the World Health Organization
      classification. Although the polyphenotype raises the issue that these may
      represent variants of MRT or the atypical teratoid-rhabdoid tumor, the
      morphologic findings in the two cases were very dissimilar. Our two cases
      underscore the problems in nosology and classification of polyphenotypic tumors
      of the CNS. This is particularly significant, as therapeutic protocols for PNET,
      MRT, and non-CNS polyphenotypic tumors are different. We review the literature on
      polyphenotypic tumors and reiterate the difficulties in precise classification of
      these complex tumors.

PMID- 9185219
TI  - Epstein-Barr virus PCR correlated with viral histology and serology in pediatric
      liver transplant patients.
AB  - Epstein-Barr virus (EBV)-associated illnesses in posttransplant patients are
      difficult to diagnose. Attempts to aid in the diagnosis of such illnesses using
      the polymerase chain reaction (PCR) analysis for EBV have met with variable
      success due to the potential exquisite sensitivity of the assay. We have designed
      a relatively insensitive EBV PCR assay and compared the results with objective
      evidence of EBV activity including serologic response and in situ hybridization
      for the EBV genome. Eighty-five specimens from 65 patients were analyzed by the
      EBV PCR using DNA from whole blood. EBV serologic evaluation was done on 53 of
      the samples and in situ hybridization for EBV (EBER-1 mRNA) on 46 paired liver
      biopsies. Of 85 samples, 25 (29%) were positive for EBV using the PCR assay.
      Intensity of amplification was graded 0.5-1+ (weak) to 3+ (strong). Using these
      criteria, 19 EBV PCR-positive samples were graded 0.5-1+, 5 were graded 2+, and 1
      was graded 3+. Of the moderate to strongly positive samples (2+ or 3+), five of
      six had two or more EBER-1-positive cells in the liver biopsies. Of the remaining
      40 liver biopsies with either negative or weak positive PCR results, 3 had only
      single cells positive for EBER-1; the remainder were negative. In addition, PCR
      positive results correlated with increasing EBV anti-early antigen antibody (P =
      .005) and viral capsid antigen IgG immunoglobulin G VCA (P = .05) EBV-positive
      results using the PCR assay correlated with objective evidence for increased EBV
      burden in children after liver transplantation. These preliminary data suggest
      that this PCR test may be useful to help guide immunosuppressive therapy in the
      posttransplant patient. Further evaluation using larger numbers of patients will
      be necessary to confirm this.

PMID- 9185220
TI  - Sex chromosome determination in extragonadal teratomas by interphase
      cytogenetics: clues to histogenesis.
AB  - Teratomas are neoplasms that are composed of tissues from all three germinal
      layers. The exact histogenetic origin of teratomas, however, is still
      controversial. In order to gain more insight into histogenesis of extragonadal
      teratomas (EGTs), the gonosomal status in 13 congenital EGTs was studied by means
      of interphase cytogenetics using nonradioactive in situ hybridization (NISH) with
      centromere-specific DNA probes. By use of this technique a direct correlation of
      cytogenetic results with morphology was possible. In all EGTs analyzed the
      gonosomal status in tissues derived from the different germinal layers was
      identical to that of the nontumorous fetal and placental tissue. This was true
      irrespective of localization, age, histological type, and classification of the
      EGT. Our results strongly suggest that EGTs arise from pluripotent diploid
      precursor cells, for example, either premeiotic germ cells that have not yet
      undergone the first meiotic division or pluripotent ectopic embryonal or
      extraembryonal cells. Our data do not support the theory of parthenogenetic EGT
      development, at least in males.

PMID- 9185222
TI  - Pathology of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the
      G1528C mutation.
AB  - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a recently discovered
      disorder affecting the mitochondrial beta-oxidation of fatty acids. There have
      been few reports of the pathologic findings in beta-oxidation defects. We
      examined pathologic specimens from 16 patients with this disorder (11 patients
      were homozygous for the common mutation G1528C, 5 patients were siblings with a
      similar clinical presentation). Autopsies were performed on all 15 patients who
      died, and liver biopsy specimens were available from 8 patients. Hepatomegaly and
      steatosis of the liver, found in every patient, were often combined with fibrosis
      or cirrhosis. Cardiomegaly and accumulation of fat in the myocardium, renal
      tubules, and skeletal muscle were found in many patients. A detailed
      neuropathologic examination was performed on six patients, and brain specimens
      obtained at autopsy were examined in four others. In general, neuropathologic
      findings were mild and unspecific, but vacuolization was detected in the deep
      gray matter and in the cerebellum and brain stem nuclei of five patients. In one
      patient the vacuolization was prominent; in the other four it was milder and more
      focal. The vacuoles seemed to be either in the neuropil or associated with
      swollen hydropic cells. The uniform pattern of histopathologic changes
      facilitates the diagnostics in this severe disorder, allowing opportunities for
      therapy and prenatal diagnosis.

PMID- 9185221
TI  - Comparison of neuropeptide Y, protein gene product 9.5, and acetylcholinesterase
      in the diagnosis of Hirschsprung's disease.
AB  - We compared the results of acetylcholinesterase (AChE) staining of mucosal rectal
      biopsy specimens with those using neuropeptide Y (NPY) and protein gene product
      9.5 (PGP9.5) in biopsies from 68 patients. Thirty-three did not have
      Hirschsprung's disease (HD), 28 had proven HD, and biopsies from 7 patients had
      shown a slight increase in AChE stain but the patients did not have HD. In our
      hands, AChE stain was superior to the other two; it was easier to read and gave
      the most accurate results with no false-positive cases and only two instances in
      which the findings were suggestive but not diagnostic. Neuropeptide Y and PGP9.5
      have the advantage that they can be used in paraffin-embedded material. With NPY,
      the results are closer than with PGP9.5 to those obtained with the AChE. Protein
      gene product 9.5 had the highest incidence of false-positive and false-negative
      results, but it stains nerve fibers and all neurons intensely and may be useful
      in the assessment of increased or decreased amounts of neural elements in the
      bowel.

PMID- 9185223
TI  - Rapidly progressive T cell lymphoma presenting as acute renal failure: case
      report and review of the literature.
AB  - We describe a case of peripheral T cell lymphoma that is remarkable for its
      fulminate course and selective targeting of both kidneys. The patient was a 6
      year-old girl who was in her usual state of good health until the onset of
      abdominal pain and fever. She was treated for acute oliguric renal failure and
      visual disturbances. A renal biopsy was performed. Biopsy findings were
      interpreted as suggestive of a vasculitic process, and treatment was initiated
      for a presumptive diagnosis of Wegener's granulomatosis. The patient died 3 days
      following admission, and autopsy revealed extensive bilateral kidney infiltration
      by a peripheral T cell lymphoma. The remainder of the body was spared with the
      exception of mild infiltration of the pulmonary parenchyma and choroid plexus by
      neoplastic lymphocytes. The neoplastic nature of the disease was confirmed
      utilizing immunoperoxidase stains and T cell receptor gene rearrangement. Primary
      renal lymphoma and renal failure attributable to involvement by lymphoma are rare
      findings that should be considered when other more common causes of renal
      insufficiency have been excluded. The presenting clinical complaints are
      generally of short duration, nonspecific, and atypical. Most patients exhibit
      oliguria. Physical examination may reveal hepatosplenomegaly, lymphadenopathy,
      and flank and/or abdominal mass(es). Laboratory findings frequently include an
      elevated serum creatinine, blood urea nitrogen, lactate dehydrogenase, and a mild
      proteinuria. Electrolyte abnormalities are variably present. Possible
      radiographic findings include hypodense or hypoechoic renal lesions and diffuse
      bilateral renal enlargement. Although the prognosis is dismal, survival may be
      prolonged utilizing current treatment modalities, and rare patients may be
      "cured" of disease. The clinical presentation, radiological findings, and
      prognosis of patients with clinically evident renal involvement by non-Hodgkin's
      lymphoma are discussed.

PMID- 9185224
TI  - Langerhans' cell granuloma confined to the bile duct.
AB  - Langerhans' cell histiocytosis (LCH) of the liver is uncommon. When seen, it is
      part of multifocal disease and can present as biliary obstruction. We present a
      case of sclerosing biliary disease with a solitary LCH lesion and no evidence of
      systemic disease. We postulate that the LCH is a secondary phenomenon, arising
      against a background of a complex, familial liver disease. This case also raises
      the possibility that some instances of idiopathic sclerosing cholangitis may
      follow cryptic LCH of the bile ducts.

PMID- 9185225
TI  - Hypereosinophilic syndrome and myocardial infarction in a 15-year-old.
AB  - The hypereosinophilic syndrome (HES) is a rare yet frequently fatal disorder of
      unknown etiology characterized by markedly elevated eosinophil counts and
      subsequent multiple organ failure due presumably to eosinophil-derived protein
      toxicity. We describe the laboratory and anatomic findings in a 15-year-old
      female with extraordinarily high circulating levels of eosinophil major basic
      protein (MBP) who sustained a precipitous cardiac death secondary to a massive
      myocardial infarction. Postmortem examination showed marked cardiomegaly with
      extensive recent left ventricular infarction. Occlusive thrombosis of small blood
      vessels was evident in the myocardium, spleen, lungs, and kidneys.
      Immunofluorescent staining showed massive MBP deposition in multiple organ
      parenchyma including the heart, renal glomeruli, adrenal cortex, bronchioles, and
      other visceral organs, suggesting a causal relationship. We hypothesize on the
      mechanisms of eosinophil toxicity in HES.

PMID- 9185226
TI  - Autopsy findings in the Wolcott-Rallison syndrome.
AB  - Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized
      by diabetes mellitus arising in early infancy and multiple epiphyseal dysplasia.
      To date, nine cases have been described in the world literature. We report an
      affected girl who died at the age of 4 years and on whom a full autopsy was
      performed. In addition to neonatal diabetes mellitus and epiphyseal dysplasia,
      this child had mental retardation and recurrent episodes of self-limiting hepatic
      failure. Autopsy revealed severe pancreatic hypoplasia and markedly abnormal
      pancreatic histology, while histology of the bone was consistent with epiphyseal
      dysplasia. There was laryngeal stenosis and pulmonary hypoplasia. The heart was
      enlarged with mitral value dysplasia and stenosis, left atrial dilatation, left
      ventricular hypertrophy, and endocardial fibroelastosis. Examination of the
      central nervous system showed arrhinencephaly and cerebellar cortical dysplasia.
      The liver showed minor histological abnormalities but no features were present to
      account for the recurrent hepatic failure. In addition to Wolcott-Rallison
      syndrome this child had a deletion at 15q11-12 in 65% of her cells.

PMID- 9185227
TI  - Crohn's disease of the prepuce in a 12-year-old boy: a case report and review of
      the literature.
AB  - We report a case of Crohn's disease with involvement of the foreskin in a 12-year
      old boy. One year previously, on the basis of clinical features (diarrhea with
      blood, perianal fissures) and histologic examination, a diagnosis of Crohn's
      disease was made. Subsequently, he developed phimosis and balanitis and underwent
      circumcision. Sections submitted from the foreskin revealed noncaseating
      granulomatous inflammation consistent with Crohn's disease. Crohn's disease with
      involvement of the genitalia is unusual. Only 26 cases including our case have
      been reported in the scientific literature. We have analyzed these cases with
      emphasis on gender, age, clinical features, duration of Crohn's disease, and
      probable mode of spread to the genitalia. Careful examination of sections from
      genital lesions, including those submitted from the foreskin, is essential to
      detect small isolated granulomas that may then lead to the diagnosis of
      inflammatory bowel disease.

PMID- 9185229
TI  - Rosai-Dorfman disease and juvenile xanthogranuloma.

PMID- 9185228
TI  - Deep juvenile xanthogranuloma: an unusual presentation.
AB  - Juvenile xanthogranuloma (JXG) is a disorder of histiocytes usually associated
      with cutaneous lesions. It may present a diagnostic dilemma in the absence of
      cutaneous lesions and when deeply located. Differentiation of JXG from other
      childhood histiocytosis syndromes, especially Langerhans' cell histiocytosis
      (LCH), is important. We describe an unusual case of deep JXG in a 27-month-old
      girl with multiple omental and peritoneal nodules presenting with ascites.
      Although a diagnosis of LCH was suspected clinically, the absence of Birbeck
      granules and S-100 protein and T6 antigen negativity, together with CD68 and
      factor XIIIa positivity, led us to a diagnosis of JXG. Physicians should be aware
      of the widening spectrum of manifestations of juvenile xanthogranuloma.

PMID- 9185230
TI  - Yellow-orange intervertebral disks in chronic obstructive jaundice in children.

PMID- 9185231
TI  - Melanoblastoma is a misnomer.

PMID- 9185232
TI  - Immunologically induced electrophysiological dysfunction: implications for
      inflammatory diseases of the CNS and PNS.
AB  - During inflammation of the central or peripheral nervous system, a high number of
      immunologically active molecules, including bacterial or viral products as well
      as host-derived cytokines, are released. Patients suffering from inflammatory CNS
      or PNS diseases often develop transient symptoms with a rapid recovery, which
      obviously cannot be accounted for by immunologically induced tissue damage. These
      observations led to the hypothesis that immunologically active molecules can
      affect directly the electrophysiological functions of neurons and glial cells.
      Evidence for this hypothesis came from in vitro studies showing that cytokines,
      such as interleukins or tumor necrosis factors, arachidonic acid and its
      metabolites, interfere with electrophysiological properties of neurons or glial
      cells. These molecules affect ion currents, intracellular Ca2+ homeostasis,
      membrane potentials, and suppress or enhance the induction and maintenance of
      long-term potentiation. Similarly, virus proteins from human immunodeficiency
      virus type I were found to alter intracellular Ca2+ concentrations of neurons and
      astrocytes by modulating either transmitter receptors and channels or membrane
      transporters. Cerebrospinal fluid from MS patients contains factors which
      increase Na+ current inactivation and thereby reduce neuronal excitability.
      Immunoglobulins in sera of patients suffering from multifocal motor neuropathy
      and from acquired neuromyotonia interfere with nerve fibers, inducing alterations
      of conduction. Increased knowledge of these mechanisms will help to explain the
      pathogenesis of neurological symptoms and may provide a rationale for new
      therapeutic strategies.

PMID- 9185233
TI  - Pharmacological aspects of human and canine narcolepsy.
AB  - Narcolepsy-cataplexy is a disabling neurological disorder that affects 1/2000
      individuals. The main clinical features of narcolepsy, excessive daytime
      sleepiness and symptoms of abnormal REM sleep (cataplexy, sleep paralysis,
      hypnagogic hallucinations) are currently treated using amphetamine-like compounds
      or modafinil and antidepressants. Pharmacological research in the area is
      facilitated greatly by the existence of a canine model of the disorder. The mode
      of action of these compounds involves presynaptic activation of adrenergic
      transmission for the anticataplectic effects of antidepressant compounds and
      presynaptic activation of dopaminergic transmission for the EEG arousal effects
      of amphetamine-like stimulants. The mode of action of modafmil is still
      uncertain, and other neurochemical systems may offer interesting avenues for
      therapeutic development. Pharmacological and physiological studies using the
      canine model have identified primary neurochemical and neuroanatomical systems
      that underlie the expression of abnormal REM sleep and excessive sleepiness in
      narcolepsy. These involve mostly the pontine and basal forebrain cholinergic, the
      pontine adrenergic and the mesolimbic and mesocortical dopaminergic systems.
      These studies confirm a continuing need for basic research in both human and
      canine narcolepsy, and new treatments that act directly at the level of the
      primary defect in narcolepsy might be forthcoming.

PMID- 9185234
TI  - Neurochemistry of the nodose ganglion.
AB  - Placode-derived general visceral afferent neurons of the nodose ganglion transmit
      visceral sensory information from specialized sensory endings of the vagus nerve
      and its branches to the nucleus of the solitary tract. These neurons are critical
      in relaying information such as elevations in blood pressure, changes in blood
      oxygenation, passage of contents through the esophagus and intestines, and
      distention of the heart, stomach, and lungs to the CNS for reflex maintenance of
      visceral functions. Multiple neurotransmitters, neuropeptides, calcium binding
      proteins, and other neuroactive substances are associated with neurons of the
      nodose ganglion. Many neurons colocalize 2 or more neuroactive substances
      creating the potential for complex interactions of neurochemical signals in the
      NTS. Neurons of the nodose ganglion also contain a variety of receptors which
      respond to transmitters, inflammatory mediators, and neurotrophic factors. The
      contents of these neurochemicals and receptors are not static as alterations in
      their expression are noted in response to epigenetic influences. Although not yet
      well understood, potential factors and mechanisms regulating neurochemical events
      in the nodose ganglion neurons are discussed.

PMID- 9185235
TI  - The neurobiology of placebo analgesia: from endogenous opioids to
      cholecystokinin.
AB  - Placebo is a widespread phenomenon in medicine and biology and its mechanisms are
      understood only partially. Most of our understanding of placebo comes from
      studies on pain. In particular, placebo analgesia represents a situation where
      the administration of a substance known to be non-analgesic produces an analgesic
      response when the subject is told that it is a pain killer. Several theories try
      to explain this effect by means of anxiety mechanisms, cognitive processes and
      classical conditioning. However, the placebo response is bidirectional, i.e.
      analgesic and algesic. In fact, if a subject is told that the ineffective
      substance is a hyperalgesic drug, a pain increase may occur. The negative effects
      of placebo are called nocebo and, in extreme cases, they lead to severe
      pathological conditions. The neurobiology of placebo was born when some authors
      discovered that placebo analgesia is mediated by endogenous opioids. This claim
      comes from the observation that the opioid antagonist naloxone can reverse
      placebo analgesia. On the basis of the discovery of the anti-opioid action of the
      neuropeptide cholecystokinin, recent studies demonstrate that the blockade of
      cholecystokinin receptors potentiates the placebo analgesic response, thus
      suggesting an inhibitory role of cholecystokinin in placebo analgesia. Thus, by
      antagonizing the anti-opioid action of cholecystokinin during a placebo
      procedure, a potentiation of the endogenous opioid systems can be obtained.

PMID- 9185236
TI  - HB-GAM (heparin-binding growth-associated molecule) and heparin-type glycans in
      the development and plasticity of neuron-target contacts.
AB  - HB-GAM is a secretory, extracellular matrix-associated protein that was isolated
      by screening for factors that enhance neurite outgrowth in rat brain neurons. The
      HB-GAM sequence clearly (about 50%) is homologous to that of MK (midkine)
      sequence, a protein discovered through screening for factors that mediate
      retinoic acid-induced cell differentiation. These lysine- and cysteine-rich
      sequences define a novel family of differentiation/growth factors, which are
      conserved in their structures from mammals to amphibians. HB-GAM is expressed
      strongly along axon pathways and target regions of axons during and prior to the
      stage of axonal growth in tissues. These findings, together with in vitro
      interactions with neurons, suggest that HB-GAM is a cell matrix-associated cue
      for growth cone migration. N-syndecan (syndecan-3) functions as a
      receptor/coreceptor in HB-GAM-induced neurite outgrowth in perinatal rat brain
      neurons. In addition to enhancing neurite growth in a developmentally regulated
      manner in early neurons, HB-GAM is accumulated at the growth cone-target
      interphase accompanying the onset of synaptogenesis, as evidenced by its presence
      at the neuromuscular junction of Xenopus and rat. In vitro studies suggest that
      HB-GAM functions as a local, synaptic matrix-associated factor that enhances both
      presynaptic and postsynaptic differentiation during development. In addition, a
      role in adult plasticity is suggested by studies on injury-induced and activity
      dependent plasticity in rat hippocampus.

PMID- 9185237
TI  - Role of the central histaminergic neuronal system in the CNS toxicity of the
      first generation H1-antagonists.
AB  - First-generation H1-antagonist-induced central toxicity often includes
      psychiatric changes, seizures and hallucinations, commonly thought to result from
      their central anticholinergic effects. Interference with the central functions of
      histamine have not been adequately addressed, despite the identification of
      histamine as a central neurotransmitter and neuromodulator. A synthesis of data
      support antagonism of H1-receptors as critical to the CNS toxicity of these
      drugs. The histaminergic neuronal system (HNS) is involved in a variety of global
      brain functions. Inherent or induced alterations in the HNS are associated with
      behavioral disorders. Clinical and experimental evidence support a role for the
      HNS in seizure protection and a relationship exits between histamine regulated
      systems and seizures. Histamine has important neuromodulatory influences on the
      central electrophysiology which underlies normal thalamocortical function. H1
      antagonists block the H1-receptor-mediated reduction of a background-leakage K+
      current (IKL) in central neurons. Secondary alterations in other ionic currents
      and alterations in synaptic responses to glutamate and GABA are produced. The non
      H1 receptor-mediated effects of histamine persist in the presence of these drugs,
      contributing to imbalances in central electrophysiology. H1-antagonist-induced
      changes are similar to the electrical disturbances thought to underly epileptic
      seizures and may adequately explain their hallucinogenic activity. These data
      form the basis for this review and must be considered as a major mechanism for
      the CNS toxicity of the first-generation H1-antagonists.

PMID- 9185238
TI  - Platelet-activating factor (PAF) in experimental and clinical sepsis.
AB  - Despite considerable progress in understanding the pathogenic mechanisms of Gram
      negative sepsis, the outcome of septic patients has not significantly improved.
      There are ample data that support a role for inflammatory mediators in sepsis
      that act in synergy with infectious agents to initiate and propagate the disease
      process. One such mediator is the glycerophospholipid platelet-activating factor
      (PAF). The objective of the present review is to summarize experimental and
      clinical evidence implicating PAF as a mediator in the pathomechanism of sepsis.
      This review is timely because many potent and selective PAF antagonists have
      matured for clinical development and a careful analysis of the data that support
      or refute the merit of clinical trials with such compounds may be important for
      both academic and pharmaceutical applications.

PMID- 9185239
TI  - Synergy and specificity in induction of gene activity by proinflammatory
      cytokines: potential therapeutic targets.
AB  - This review focuses on two important routes of gene activation mediated by
      proinflammatory cytokines, which serve as a paradigm for mechanisms of
      specificity and synergy in cytokine regulated gene activity: STAT (signal
      transducers and activators of transcription)-related gene activation and the
      pathways initiated by proinflammatory cytokines leading to the activation of the
      NF-kappa B family of transcriptional activators. The proinflammatory cytokine
      cascade is involved in both the normal immune response and in the pathogenesis of
      several disease states. An understanding of specificity and synergism in these
      pathways offers an opportunity to develop novel therapeutic drugs for the
      selective manipulation of these disease processes. Such potential targets are
      examined in this review.

PMID- 9185240
TI  - Clinical application of ventricular end-systolic elastance and the ventricular
      pressure-volume diagram.
AB  - The ability to clinically assess myocardial contractility in a load-independent
      fashion facilitates the selection of appropriate inotropes, when needed, during
      shock resuscitation. Within the framework of the ventricular pressure-volume
      diagram, the slope of the ventricular end-systolic pressure-volume relationship
      (expressed as ventricular end-systolic elastance, Ees), has been shown to
      accurately reflect ventricular inotropic state, and to be insensitive to loading
      conditions. It has not, however, been widely used at the bedside. Our goal was to
      evaluate the clinical utility of Ees and the ventricular pressure-volume diagram
      as bedside methods of hemodynamic assessment. We performed a prospective study of
      123 hemodynamic interventions in 100 trauma patients during shock resuscitation
      in which contractility (Ees), preload (left ventricular end-diastolic volume
      index), and afterload (effective arterial elastance) were calculated before and
      after addition of inotropes, fluid bolus, and afterload reduction. Mean values of
      each variable were compared before and after each type intervention using the
      paired t test. The ventricular pressure-volume diagram was used to predict
      changes in the studied variables, and the experimental results were compared with
      predicted changes. Ees (mmHg/mL/m2) increased significantly with inotropes (4.7
      +/- 3.2 to 10 +/- 8.7, p < .0001), but was not affected by clinically significant
      fluid administration (7.0 +/- 4.7 to 8.3 +/- 8.0, p = .10) or afterload reduction
      (9.6 +/- 5.2 to 9.2 +/- 4.7, p = .72). Left ventricular end-diastolic volume
      index (mL/m2) improved with fluid administration (54 +/- 8.9 to 62 +/- 9.8, p <
      .0001) and effective arterial elastance (mmHg/mL/m2) decreased with afterload
      reduction (3.3 +/- .9 to 2.6 +/- .7, p < .0001). We conclude that Ees is a load
      independent measure of contractility, which is measurable at the bedside. The
      pressure-volume diagram is a useful method of monitoring hemodynamic changes
      associated with interventions during shock resuscitation.

PMID- 9185241
TI  - Clinical application of ventricular end-systolic elastance and the ventricular
      pressure-volume diagram.

PMID- 9185242
TI  - Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein
      (CRP), and endotoxin plasma levels during the postoperative acute phase reaction.
AB  - During goitre surgery (25 patients) and after major abdominal surgery (52
      patients), we studied the plasma levels of endotoxin, interleukin-6 (IL-6), C
      reactive protein (CRP), and the so called myeloid-related proteins (MRP), MRP8,
      MRP14, and the heterocomplex of both single proteins, MRP8/MRP14 in three
      intervals: pre-, intra-, and postoperative. We observed that CRP levels began to
      increase on the first postoperative day, reaching a maximum on day 2 (median
      levels of 185 mg/L after major surgery and 77 mg/L after goitre surgery). IL-6
      levels peaked at the end of the operation, remaining elevated for 6 h following
      abdominal surgery (299 pg/mL) and peaked on day 1 after goitre surgery (63
      pg/mL). An increase in MRP8/MRP14 levels began toward the end of abdominal
      surgery, and maximum levels were recorded until 5 days after the operation (5,695
      micrograms/L). Plasma levels were significantly elevated 2 and 6 h after minor
      surgery (3,619 micrograms/L), while no changes were observed in the plasma levels
      of MRP8 and MRP14. Evidence of significant endotoxemia was found after the
      induction of anesthesia in the abdominal surgery group (.13 endotoxin units
      (EU)/mL) and after skin incision (.07 EU/mL) in the thyroid surgery group. The
      observed time sequence, starting with the release of bacterial products at an
      early stage, followed by the secondary stimulation of factors inherent to the
      acute phase led us to conclude that certain bacterial compounds, probably
      deriving from the gastrointestinal tract, trigger the postoperative acute phase
      reaction and are responsible for the activation of monocytes/macrophages and
      granulocytes.

PMID- 9185243
TI  - A matrix metalloproteinase inhibitor prevents processing of tumor necrosis factor
      alpha (TNF alpha) and abrogates endotoxin-induced lethality.
AB  - Excessive tumor necrosis factor alpha (TNF alpha) production in response to Gram
      negative bacteremia or endotoxemia can often lead to hypotension, shock, and
      increased mortality. Current approaches used to block the deleterious effects of
      exaggerated TNF alpha production rely on monoclonal antibodies or immunoadhesins
      that bind TNF alpha and thus prevent the interaction with its cellular receptors.
      This report examines whether a previously described inhibitor of matrix
      metalloproteinases, GM-6001, can inhibit TNF alpha processing and release and
      attenuate endotoxin-induced mortality. In human peripheral blood mononuclear
      cells stimulated in vitro with 1 microgram/mL endotoxin, GM-6001 at
      concentrations > 5 micrograms/mL blocked release of TNF alpha, but did not affect
      the release of either IL-1 beta or IL-6. GM-6001 also inhibited the release of
      soluble TNF receptor (p75) from peripheral blood mononuclear cells stimulated
      with endotoxin and/or TNF alpha. To confirm the role of secreted TNF alpha in
      endotoxic shock-induced mortality, C57BL/6 mice were challenged with either
      endotoxin alone (500 micrograms/mouse) or endotoxin (100 ng/mouse) plus D
      galactosamine (8 mg/mouse). GM-6001 pretreatment (100 mg/kg) significantly
      attenuated the 90-minute plasma TNF alpha response in both models and improved
      survival in mice treated with low-dose endotoxin plus D-galactosamine. However,
      plasma IL-1 beta and IL-6 concentrations at 90 min after endotoxin treatment were
      unaffected by GM-6001 following lethal endotoxin challenge, confirming the in
      vivo specificity of this matrix metalloproteinase inhibitor for TNF alpha
      processing. These findings demonstrate that a novel inhibitor of matrix
      metalloproteinases can prevent the release of TNF alpha both in vitro and in
      vivo, and can abrogate the harmful sequelae of endotoxemic shock.

PMID- 9185244
TI  - Modulation of skeletal muscle lactate metabolism following bacteremia by insulin
      or insulin-like growth factor-I: effects of pentoxifylline.
AB  - Hyperlactatemia is a frequent complication of sepsis. We investigated the effect
      of pentoxifylline on plasma lactate concentrations and lactate release by
      epitrochlearis incubated in vitro following intravenous injection of Escherichia
      coli. Plasma lactate concentrations were elevated on day 2 postinfection and
      remained elevated for at least another 4 days. Lactate production by incubated
      epitrochlearis was not increased in septic rats on day 2 postinfection, and
      lactate production from muscles incubated with insulin (2 nM) or insulin-like
      growth factor-I, (10 nM) was similar in control and septic rats. On day 6
      postinfection, lactate production was augmented 1.8-fold in muscles from septic
      rats and both insulin and IGF-I caused an exaggerated stimulation of lactate
      production compared with control. Pentoxifylline decreased plasma TNF
      concentrations 100-fold following injection of bacteria and prevented the sepsis
      induced hyperlactatemia and increase in lactate production by incubated muscles
      in presence or absence of insulin or IGF-I. Thus, pentoxifylline prevented the
      sepsis-induced abnormalities in skeletal muscle lactate production and plasma
      lactate concentrations.

PMID- 9185245
TI  - Evidence that adenosine contributes to maintenance of hepatosplanchnic blood flow
      during peritoneal sepsis in rats.
AB  - Sepsis induced derangements in hepatosplanchnic perfusion can contribute to organ
      damage and death. Adenosine, a common and potent metabolic vasodilator, has not
      been evaluated as a mechanism for maintenance of blood flow during sepsis. We
      tested the hypothesis that adenosine receptor blockade would cause a decrease in
      hepatosplanchnic blood flow during intraperitoneal (i.p.) sepsis in the rat. Rats
      (250-350 g) were catheterized for hemodynamic and blood flow measurements with
      tracer microspheres. Sepsis was induced with an i.p. injection of cecal material
      (150 mg/kg in D5W; 5 mL/kg), and baseline measurements were taken 24 h later.
      Animals then received either the adenosine receptor antagonist 8-PTH (10 mM, 1.5
      mL/kg), its vehicle (1.5 mL/kg) or normal saline (1.5 mL/kg), intravenously, and
      measurements were repeated 1 and 10 min later. There was a significant increase
      in hepatosplanchnic portal resistance in septic animals given 8-PTH, with no
      change in mean arterial blood pressure (MAP) or heart rate. Regionally, there was
      a significant decrease in gastric, small intestinal, cecal, and pancreatic blood
      flow when compared with vehicle. Adenosine receptor blockade caused a significant
      reduction in hepatosplanchnic blood flow during sepsis, suggesting that
      maintenance of splanchnic blood flow during sepsis involves receptor mediated
      adenosine actions.

PMID- 9185246
TI  - The effect of anti-L-selectin (EL-246) on remote lung injury after infrarenal
      ischemia/reperfusion.
AB  - The clinical concern in using neutrophil adhesion blocking agents is whether or
      not neutrophil function may be down-regulated, rendering neutrophils incapable of
      dealing with infections that may threaten the patient. In a sheep model of
      ischemia and reperfusion, we have investigated the effect of anti-L-selectin (EL
      246) on the pulmonary injury as well as on the neutrophil function, assessed by
      in vitro chemiluminescence (CL) of isolated neutrophils. Infrarenal ischemia (3
      h) followed by reperfusion (4 h) resulted in pulmonary capillary leakage as
      evident by an increased alveolar/plasma protein ratio (.76 vs. .19 in control, p
      < .01) and also led to a significant pulmonary neutrophil accumulation as
      assessed by the myeloperoxidase content in homogenized lung tissue (31.7 vs. 6.1
      U, p < .01). Anti-L-selectin, infused at a dose of 1 mg/kg at the time of
      reperfusion, significantly reduced the pulmonary leakage by 59% (.42 vs. .76 U)
      and neutrophil accumulation by 84% (10.2 vs. 31.7 U). Pulmonary function improved
      by anti-L-selectin as represented by an increase of the arterio-venous oxygen
      ratio. CL decreased from 1.85 x 10(5) counts(c)/min to 1.02 x 10(6) c/min at 15
      min of reperfusion in the positive control followed by a subsequent return to
      normal. In contrast to myeloperoxidase, the significant change in CL was not
      affected by the use of anti-L-selectin. Based on our data, we conclude that anti
      L-selectin is able to significantly reduce the pulmonary injury in ischemia
      reperfusion but in parallel does not result in neutrophil dysfunction regarding
      for example, the respiratory burst. Thus, using neutrophil adhesion blocking
      agents in patients appears to be unlikely to increase the risk of septic
      complications.

PMID- 9185247
TI  - Satisfying consumer choice: a quality issue in the health sector.

PMID- 9185248
TI  - Lymphocyte immunophenotype reference ranges in healthy Thai adults: implications
      for management of HIV/AIDS in Thailand.
AB  - Lymphocyte immunophenotype reference ranges for T, B, and NK subsets were
      determined for healthy adult Thais in a multi-center study in Bangkok.
      Immunophenotyping was by flow cytometry using lysed whole blood. A standard
      protocol for flow cytometry instrumentation, reagents and quality control was
      used to minimize site differences and to facilitate comparison of the Thai
      reference values to those found for Caucasians in previous studies. Major
      differences were determined for CD3(T), CD4 (T helper/inducer) and CD16+56 (NK)
      lymphocyte percentages and CD4 lymphocyte absolute counts. Age trends and sex
      differences were also observed. Compared to Caucasians, Thais, particularly Thai
      males, had lower CD3 and CD4 T lymphocyte percentages and absolute numbers
      whereas the percentage of NK lymphocytes was higher. Heterogeneity attributed to
      biological variation of CD4 T lymphocyte but not other immunophenotype subset
      distributions was also observed in a well defined geographic population. This
      study demonstrates the importance of ethnicity, age, sex and possibly environment
      as factors that influence distribution characteristics of normal lymphocyte
      immunophenotype reference values. These observations have important implications
      for the use of lymphocyte subsets-particularly CD3+ CD4+ T lymphocyte
      measurements as applied to HIV disease staging, AIDS definition and the overall
      clinical management of HIV/AIDS in Thailand.

PMID- 9185250
TI  - High risk behavior related to HIV transmission among recently diagnosed TB
      patients in Jakarta.
AB  - This study investigated the demographic and high risk behavior characteristics
      among recently diagnosed pulmonary tuberculosis patients aged 18-40 years old in
      Jakarta, Indonesia. Three hundred and four participants were recruited
      voluntarily from two general hospitals. Among the study population, 38.5% were
      unemployed, 69.7% were in low socio-economic condition, and 69.7% had a high
      school or higher level of education. About 8% had received a transfusion, 0.3%
      were intravenous drug users (IVDU) and had sex with other IVDU's no males
      admitted to being homosexual, 3.2% of males were bisexual, 20.1% (35.5% of males,
      4% of females) engaged in extramarital heterosexual intercourse, and 3.6% (7.1%
      of males) had one or more sexually transmitted diseases (STD). We found very
      strong associations between gender and extramarital heterosexual activity (p <
      0.001, prevalence odds ratio (POR 13.11), between occupation and extramarital
      heterosexual activity (p < 0.001, POR 3.84), and between extramarital
      heterosexual contact and a history of an STD (p < 0.001, POR 20.86). High risk
      activities were common among these TB patients, especially among males. These
      results suggests that the necessary social conditions for transmission of HIV are
      common in Jakarta.

PMID- 9185249
TI  - Evaluation of HIV/AIDS education initiatives among women in northeastern Thai
      villages.
AB  - A longitudinal, naturalistic experimental design was used in an evaluation of the
      effects of an HIV/AIDS educational pamphlet controlling for secular trends (most
      specifically media coverage of HIV/AIDS) in Northeastern Thailand. Nine hundred
      and fifty-four women from 18 villages completed KAP interviews either in the
      autumn of 1991 or 1992 with HIV/AIDS education pamphlets distributed to every
      household in 12 of these villages in the spring of 1992. Pamphlets influenced
      women's perceptions of personal risk from casual sources and the degree to which
      they volunteered that condoms were a means of prevention of HIV transmission.
      Both results were related to the content and style of presentation of information
      about sources of risk and about condoms in the pamphlets. Secular trends and an
      increase in communication between villagers had a significant influence on
      knowledge, perceived efficacy of self protection, readiness to use condoms, and
      perception of levels and sources of personal risk.

PMID- 9185251
TI  - HIV prevalence in upper socioeconomic level hospital patients, 1991-1993.
AB  - Five elite, private hospitals in Bangkok serving the upper socioeconomic stratum
      of Thai society were sampled for HIV prevalence among unlinked, anonymous
      specimens collected from general inpatients (sampled 11/1991 to 1/1992) and from
      women in labor (sampled 5/1992 to 4/1993). The HIV-1 antibody positivity rate by
      ELISA/Western blot was 0.45% (9 of 2,000) among all inpatients, and 0.1% (1 of
      1,000) among pregnant women. The latter rate was appreciably lower than rates
      between 1 and 2% found in sentinel surveys among pregnant women in public
      hospitals during comparable time periods, suggesting the epidemic is more
      advanced in lower socioeconomic groups.

PMID- 9185252
TI  - Reducing the risk of HIV transmission through blood transfusion by donor self
      deferral.
AB  - A cross sectional study was conducted to evaluate the validity of implementing a
      blood donor self-deferral form for reducing the risk of HIV transmission through
      blood transfusion. The self-deferral form which was given to all blood donors,
      included questions about HIV risk factors in the three month period prior to
      blood donation. Donors were asked to declare confidentially whether their blood
      was safe for transfusion or not. Blood was collected and examined for HIV
      antigen, anti-HIV antibodies, HBsAg and syphilis antibodies. All of the
      serological markers detected among high risk donors and general donors were
      compared and analysed by Yates corrected X2 test and one-tailed Fisher's exact
      test with a significance level of 0.05. There were 401 self-deferred high risk
      donors and 15,523 general donors. The HIV antigen was found as a single marker in
      only one male high risk individual. The prevalence of anti-HIV antibodies, HBsAg
      and syphilis antibodies among the general donors was 0.61%, 5.29% and 1.17%,
      respectively. The anti-HIV, HBsAg and syphilis antibodies in the high risk donors
      were 1.99%, 7.98% and 1.25%, respectively. In comparison with the general donors,
      the high risk donors demonstrated statistically significant higher prevalence
      rates of HIV antigen (p < 0.05), anti-HIV (p < 0.005) and HBsAg (p < 0.05). In
      conclusion, donor self-deferral is valid for reducing the risk of HIV
      transmission through blood transfusion and its implementation should be
      encouraged when recruiting blood donors.

PMID- 9185253
TI  - Feasibility of northern Thai factory workers as participants in HIV vaccine
      trials.
AB  - To determine the feasibility of establishing a cohort of HIV-1 seronegative
      factory workers for potential HIV vaccine trials, and other HIV preventive
      interventions, we enroled and followed 499 male and female industrial workers in
      Lamphun Province, northern Thailand. A baseline demographic and HIV
      seroprevalence survey was conducted by a mobile team at worker's housing units in
      Lamphun Province in 1994. Follow-up HIV and syphilis incidence rates were
      measured 6 months later. The study was voluntary, anonymous, and included HIV pre
      and post-test counseling, HIV and syphilis serology, and a self-administered
      fact sheet. A total of 106 men and 393 women were recruited. The median age was
      22 years, and the mean 23.4 years. Educational levels were moderate; 41.9% had
      some secondary school and 23.6% had completed secondary school. HIV prevalence
      was 2.4% overall but differed by sex; among men it was 7/106, 6.6%, among women
      5/393, 1.3%, OR = 5.49 (95% CI = 1.52, 20.39). Low educational levels were
      associated with HIV infection, OR = 7.2 (95% CI = 2.2, 23.4). Syphilis prevalence
      was 3.8%. Follow-up at 6 months was successful for 420/499 subjects, 84.2%, and
      varied by sex: 73/106 men, 68.9%, returned while 347/393 women, 88.3%, did so, RR
      = 1.21 (95% CI = 1.07, 1.37). There were 5 incident HIV-1 infections, a rate of
      2.1/100 person years. The HIV seroconversion rate differed by sex, but not
      significantly; it was 4.1/100 person years for men and 1.5/100 person years for
      women. This population is largely young, female, and at considerable HIV risk. If
      follow-up could be improved, factory workers in northern Thailand could be an
      appropriate population in which to mount HIV preventive efficacy studies,
      including vaccine trials.

PMID- 9185254
TI  - Cross-sectional serosurvey for Japanese encephalitis specific antibody from
      animal sera in Malaysia 1993.
AB  - Serum specimens were collected from 6 species of animals living in 9 states of
      Malaysia including Sabah, North Borneo in 1993. Antibodies against Japanese
      encephalitis (JE) virus in these sera were detected by means of hemagglutination
      inhibition (HI) and neutralization (NT) tests. By HI test, 702 of 2,152 (32.6%)
      sera showed positive results. Higher positive rates were obtained by the NT test,
      in which 1,787 of 1,927 (92.7%) sera had antibodies against JE virus. All serum
      specimens with positive HI were confirmed as positive by the NT. Swine sera
      showed especially higher rates of antibody positive and higher antibody titers
      compared with other animals. These results suggest that JE infections are widely
      distributed among many animals of Malaysia, and pig is the most susceptible
      amplifier host for JE virus.

PMID- 9185255
TI  - Hemorrhagic manifestations and encephalopathy in cases of dengue in India.
AB  - Thirty-seven serum samples and five serum-CSF pairs collected from 42 acutely ill
      patients admitted to hospitals in Maharashtra (Bombay, Pune and Nasik); Orissa
      (Raurkela) and South Goa were referred to the National Institute of Virology
      (NIV), Pune (Maharashtra, India) for serodiagnosis. These patients had clinical
      manifestations of fever, hemorrhagic manifestations, hepatomegaly, shock syndrome
      and encephalopathy. Sixty-six percent of patients were children below ten years
      of age. Serological investigations revealed infection to dengue virus in all the
      patients as indicated in detection of IgM antibodies predominantly to dengue
      viral antigens. An important outcome of the study is that 10 patients referred to
      NIV with a provisional diagnosis of viral encephalitis proved to be dengue.

PMID- 9185256
TI  - Serum trace metal levels in patients with acute hepatitis B.
AB  - This study was conducted to determine serum levels of trace metals in young adult
      patients in the early icteric phase of acute hepatitis B virus infection. There
      were 15 patients (10 males, 5 females) and 15 healthy volunteers (11 males, 4
      females). The age distribution of both groups ranged from 15-40 years and were
      comparable [mean (SD) = 28(6) vs 31(7) years; p = 0.12]. Compared to the healthy
      controls, the patients had significantly decreased serum zinc but elevated serum
      copper levels [means (SD) of zinc = 118(22) vs 97(20) micrograms/dl, p = 0.012;
      and of copper = 82(15) vs 135(40) micrograms/dl, p < 0.001]. The overall serum
      levels of calcium, magnesium and phosphorus in the studied patients were within
      normal ranges. Serum zinc concentrations of these patients correlated with
      albumin (r = 0.69, p = 0.005) and their serum calcium correlated with alkaline
      phosphatase (r = 0.61, p = 0.015). These results demonstrate that alterations of
      zinc and copper metabolism occur early during the acute icteric phase of
      uncomplicated hepatitis. These changes may be of pathophysiological significance
      in acute hepatitis, in particular in patients with pre-existing zinc deficiency.

PMID- 9185257
TI  - Methodological issues in conducting a survey of construction workers in
      northeastern Thailand.
AB  - Social and health problems among the construction workers in Thailand were
      studied in a multicenter cross-sectional survey. This paper documents
      methodological issues related to conducting the survey in the northeastern
      Thailand. These issues include defining suitable sampling frames for building
      sites and workers and collecting data. A number of practical problems and the
      approaches to solve them are discussed.

PMID- 9185259
TI  - Clinical trial of intramuscular anti-snake venom administration as a first aid
      measure in the field in the management of Russell's viper bite patients.
AB  - Efficacy of intramuscular anti-snake venom administration immediately after bite
      as a first aid measure in the field followed by standard hospital management
      versus standard hospital management alone in the therapy of Russell's viper bite
      patients was studied. There was a definite reduction in the number of patients
      with systemic envenomation, complications following disseminated intravascular
      coagulation and in fatality rate of Russell's viper bite victims who had received
      first aid intramuscular anti-snake venom prior to hospitalization when compared
      with those who had not.

PMID- 9185258
TI  - Cervical cancer screening in Bali: a public health issue.
AB  - Cervical cancer is the most common cancer in women in developing countries.
      Regarding cervical cancer in Bali, we sought to determine the incidence, to
      evaluate existing preventive and screening programs, to identify the population
      being screened, and to examine the methods of testing. The records of the Udayana
      Teaching Hospital pathology laboratory and Cancer Registry were reviewed,
      retrospectively. The incidence of cervical cancer in Bali is 7/100,000. There has
      already been a substantial increase in the number of Papanicolaou tests (PT) from
      767 in 1990 to 1,355 in 1992. In 63% of these tests the results were Class II,
      indicating a need for attention to infection. Cervical intraepithelial neoplasia
      has a statistically significant increase with age. The number of PT performed
      peaks in the 35-44 year age group, with a sharp decline thereafter. Fifty-four
      percent of PT are performed in the capital city, which has only 20% of the female
      population. Bali Hindu women make up 94% of the female population, but receive
      only 81% of PT, while Muslim women make up 5% of the population and receive 12%
      of PT. Seventy-eight percent of PT contain no endocervical cells. There has
      already been a promising increase in the number of PT performed in Bali. Public
      health promotion efforts as well as outreach programs should be expanded, perhaps
      using the Banjar system, to reach older and rural women. Collectors of Pap smears
      should be instructed on the importance of endocervical sampling.

PMID- 9185260
TI  - Historical review of mosquito control as a component of malaria eradication
      program in the Ryukyu Archipelago.
AB  - In the Ryukyu Archipelago, where malaria used to be endemic, eradication of the
      disease was achieved by the year 1962, as a consequential effect of a planned
      malaria eradication program in the area. This achievement was facilitated by
      concerted efforts in controlling vector mosquitos and treatment of all detected
      and presumptive cases of malaria infections. Anopheles minimus Theobald and An.
      sinensis Wiedemann were common in all areas endemic for malaria. Knowledge of the
      biology and bionomics of the mosquitos in malaria endemic areas formed the basis
      for formulating strategies for the control of vectors and subsequent surveillance
      activities. Insecticide residual spray, larvivorous fishes and environmental
      management were the basic strategies for vector control. The whole program was
      augmented by an active community participation in all eradication activities.

PMID- 9185261
TI  - Sustainability of a successful malaria surveillance and treatment program in a
      Runggus community in Sabah, east Malaysia.
AB  - The district of Kudat has one of the highest and most persistent malaria
      transmission levels in Sabah, Malaysia, with annual parasite incidence of 102 per
      1,000 inhabitants per year. Due to this situation and the failure of DDT spraying
      to control malaria, a community participation health program (Sukarelawan
      Penjagaan Kesihatan Primer or SPKP) was developed as an adjunct to current anti
      malarial measures during 1987-1991. SPKP is made up of unpaid community workers
      known as village health volunteers (VHVs). VHVs are selected by a village
      development and security committees training and supervision a member of the
      Vector-Borne Diseases Control Program (VBDCP). The beneficiaries of SPKP
      consisted primarily of Runggus people and other remote, and mobile populations
      who visit the home of a VHV for diagnosis and treatment. This group of febrile
      patients and their children who attend a participating school submit finger prick
      blood and personal details to the VHV. and receive a presumptive treatment for
      malaria. Thick and thin blood smears are examined by a VBDCP microscopist who
      then prepare and forward a radical or curative treatment to the VHV so that it
      can be administered to the microscopically-positive patient free of charge.
      Between June 1987 to June 1991, VHVs from 32 kampungs (villages) and 22 schools
      collected 56,245 slides representing 24.7% of total slide collection compared to
      74.9% collected by passive case detection (PCD) posts in health centers and
      district hospital. The average volunteer treated 11.8 (range 10.4-13.4) and 31.4
      (range 26-49) patients per month in kampungs and schools respectively. In
      contrast, non-SPKP posts in a district hospital, health centers and flying doctor
      service treated an average of 616.3 patients per month (range 134.8-1032.8). The
      slide positivity rate of blood smears taken by VHVs was 8.43% compared with 7.37%
      for non-SPKP posts. Average slide collection and slide positivity rates varied
      considerably from one community to another, despite their close geographic
      proximity. The monthly number of VHV-diagnosed patients from the school and
      kampungs communities and the monthly number of true malaria patients in the two
      groups were significantly correlated. Sustainability of SPKP was linked to an
      ongoing process of social change which involved co-operative networking between
      the government health sector and the community. This in turn provided a stimulus
      for malaria abatement efforts. When Runggus people themselves control and
      maintain ownership of community-based malaria programs, the function of SPKP as a
      malaria surveillance system and an antimalarial drug distribution network is
      vastly improved.

PMID- 9185263
TI  - Morbidity and mortality due to malaria in Tarajulie Tea Estate, Assam, India.
AB  - Beginning 1991, a sudden rise of malaria cases were recorded in Tarajulie TE
      (Assam) coupled with mortality due to malaria. Deaths were confirmed due to
      Plasmodium falciparum (Pf) infections and were recorded in all age groups
      excluding infants. Malaria positives were recorded in all months of the year,
      however, there was a increased hospital attendance due to fever/malaria positives
      during May to September. During the years (1991-1993), the slide positive rate
      was as high as 33.04%, mostly being Pf infections (69%), and the annual parasite
      index ranged between 6 to 304 per thousand population. Morbidity and mortality
      due to malaria were attributed to labor movements to and fro from garden premises
      to adjoining hamlets, the latter being the site of acquisition of the infections.

PMID- 9185262
TI  - Activity of artemether-azithromycin versus artemether-doxycycline in the
      treatment of multiple drug resistant falciparum malaria.
AB  - The efficacy of the combination of artemether with doxycycline or azithromycin
      was evaluated in 60 patients with acute uncomplicated falciparum malaria who
      attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients
      (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg
      doxycycline as initial doses, followed by 100 mg artemether plus 100 mg
      doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another
      4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by
      250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days.
      Patients in either group had a rapid initial response to treatment with
      comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was
      significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%).
      Low cure rate from artemether-azithromycin combination in this study was likely
      to be due to inadequate azithromycin dosage. However, with the low incidence of
      gastrointestinal adverse effects, the once daily dose of azithromycin could still
      be increased in order to enhance its clinical efficacy. The simplicity of drug
      administration and lesser incidence of adverse effects make azithromycin a more
      proper partner of artemether than doxycycline. Further dose-finding and
      pharmacokinetic study with the artemether-azithromycin combination is
      encouraging.

PMID- 9185264
TI  - Temporary appearance of a circulating granulocyte-macrophage colony-stimulating
      factor in lethal murine malaria.
AB  - Infection of mice with Plasmodium berghei engendered a temporary appearance of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum. The peak
      of GM-CSF levels was detected at day 2 post-infection, and then gradually
      decreased. On the other hand, the number of committed stem cells for granulocytes
      and macrophages (CFU-GM) in bone marrow transiently decreased at day 2 post
      infection, and then increased and peaked at day 6 post-infection. When the serum
      of P. berghei-infected mice was fractionated by gel chromatography on Sephacryl S
      300, GM-CSF activity was detected as a single peak with an apparent molecular
      weight of 64 KDa. GM-CSF was entirely adsorbed to concanavalin A-Sepharose 4B
      affinity chromatography, and was sensitive to pronase digestion, indicating its
      glycoprotein nature. These results suggest that the circulating GM-CSF would
      contribute the increase of granulocyte-macrophage hemopoiesis in the early phase
      of malaria.

PMID- 9185265
TI  - The effect of a combined approach to schistosomiasis control on the transmission
      of Schistosoma japonicum in Xingzi of Poyang Lake area, China.
AB  - The impact of a combined approach to schistosomiasis control from 1987 to 1989
      and mass chemotherapy from 1992 to 1994 was studied in a rural community in
      Xingzi county in the northwest corner of Poyang Lake in Jiangxi Province, China.
      Humans, cattle, buffalo and pigs were known potential reservoirs of Schistosoma
      japonicum. Transmission occurs during water contact on and around seasonally
      flooded marshes that are used for grazing, the harvesting of grass and fishing.
      Humans and livestock underwent yearly selective mass chemotherapy, and snails
      were eliminated through ploughing and compacting of the marshland in the spring
      of 1988. Transmission was monitored through the determination of annual re
      infection rates in samples of the human population, the annual examination of
      piles of feces from animals and humans in the marshland, the annual collection
      and examination of intermediate snail hosts, and the exposure to potentially
      polluted water and subsequent examination of sentinel mice. Schistosomiasis
      prevalence among humans and animals declined sharply as soon as mass chemotherapy
      was implemented. Snail density decreased even before mollusc control was started,
      possibly indicating a high variability of this indicator. The infection rates of
      snails and sentinel mice reached zero after a single application of mollusc
      control. The results underline the importance of single infected water buffalo
      for the transmission of schistosomiasis. Since the impact stopped for two years
      (1990-1991), the schistosomiasis prevalence rose quickly. Mass chemotherapy was
      an effective means to curb the prevalence of schistosomiasis in this area, but
      the effects were only maintained for one or two years in the marsh zone.

PMID- 9185266
TI  - A survey of Gnathostoma larvae in fresh water fish in the valley of the Yangtze
      River and morphological characteristics of the recovered larvae.
AB  - Investigations of the prevalence of larval gnathostomes in fresh water fishes
      were carried out at the southeastern Yangtze Valley, People's Republic of China,
      in the periods of October 1989 and November 1990. Fishes were collected from
      Shanghai, Chenchiang, Nanching, Chiuchiang and Nanchang districts in 1989.
      Additional sampling in Shanghai district was done at Kunshan, Tien-shanfu,
      Chingpu and Nanhui. Species of fishes collected were Channa argus (110),
      Siniperca chuatsi (24) and Silurus asotus (2). Muscle tissue of the fishes was
      dissected into small pieces, sliced and then examined under a dissecting
      microscope. The viscera were pooled by species in groups of 4 or 5 individuals,
      homogenized, and were then digested overnight in artificial gastric-juice at 37
      degrees C. Four encysted larvae were recovered from the muscle tissue of four C.
      argus. Thirty-four larvae were obtained from digestion of viscera. A total of 38
      larvae were recovered. Eighteen of 38 larvae were examined morphologically and
      they were able to be divided into three types by their body length; 5 early third
      stage larvae (0.58-0.86 mm), 12 third-stage larvae (1.12-2.61 mm), and one
      advanced third-stage larva of 4.86 mm. Light and scanning electron microscopy
      revealed that the former two types had characteristics of Gnathostoma hispidum
      and the last one had those of G. spinigerum. In 1990, we investigated fish near
      Hongtze-hu and Tai-hu lakes. A total of 553 fishes belonging to 12 genera and 12
      species were examined. Seventeen larvae were recovered from the viscera of G.
      argus and Monopterus albus. These larvae were identified as G. hispidum.

PMID- 9185267
TI  - Seroepidemiological study of Toxoplasma infection in central and western regions
      in Nepal.
AB  - The present study was carried out to ascertain the seroprevalence rate in
      different geographical areas in Central and Western Regions in Nepal. A total of
      1,237 serum samples collected from Nuwakot (217), Kathmandu valley (402) and
      Chitawan (159) districts in Central Region, and Mustang (143), Surkhet (64) and
      Banke (252) districts in Western Region in Nepal were included in this study.
      Toxoplasma antibodies were detected by micro-latex agglutination (MLA) and enzyme
      linked immunosorbent assay (IgM-ELISA) methods. The seropositive rate in Central
      and Western Regions were found to be 48% and 49%, respectively; with an overall
      positive rate of 48 percent. Districtwise, the seropositive rate in Nuwakot,
      Kathmandu valley, Chitawan, Mustang, Surkhet and Banke districts were 38, 46, 64,
      51, 67 and 44%, respectively. Interestingly, the relatively newly inhabited
      Surkhet district in Western Region and Chitawan district in Central Region showed
      significantly higher seropositive rate compared with those of two other districts
      in the respective Regions (p < 0.05). Ethnically, Tibeto-Burmans showed higher
      seropositive rates in Central Region (p > 0.05). In contrast, Indo-Aryans showed
      higher seropositive rate in Western Region (p > 0.05). Age related increase in
      seropositivity was observed only in Central Region. One percent of Toxoplasma
      antibody positive samples also showed Toxoplasma IgM antibody positivity.

PMID- 9185268
TI  - A survey of Toxoplasma gondii antibodies in goats and cattle in Lampung province,
      Indonesia.
AB  - A survey for antibodies to Toxoplasma gondii using latex agglutination test (LAT)
      was carried out from November 1994 to March 1995 in several areas of Lampung
      Province, Sumatra Indonesia with seropositivity rates of 47.5% in 160 goats and
      9.0% in 200 cattle. Twenty-six out of 78 positive goats had a maximum antibody
      titer of more than 1:2,048. In case of cattle, the maximum antibody titer was
      1:128.

PMID- 9185269
TI  - Seroepidemiology of five major zoonotic parasite infections in inhabitants of
      Sidoarjo, East Java, Indonesia.
AB  - We conducted a seroepidemiological survey of zoonotic parasite infection in
      inhabitants of East Java, Indonesia. The subjects of the survey were 244 persons
      selected from visitors to Sidoarjo City Hospital in East Java between May 1992
      and October 1993. Ninety-seven had diarrhea and the rest came to the hospital for
      routine check-ups. All serum samples were tested for antibodies against five
      zoonotic parasites: Toxoplasma gondii, Entamoeba histolytica, Toxocara canis.
      Angiostrongylus cantonensis, and Anisakis species. Tests used were enzyme-linked
      immunosorbent assays (ELISA), latex agglutination (LA) test, indirect
      fluorescence antibody (IFA) test, hemagglutination (HA) test, and gel diffusion
      precipitation (GDP) test. Some 64% of the subjects had antibodies to T. gondii.
      The prevalence of antibodies to E. histolytica varied from 2 to 15% depending on
      the test, but the true rate was probably the 7% or 8% obtained by the HA and IFA
      tests. The proportions of subjects with positive results were 63% for T. canis,
      17% for A. cantonensis, and 11% for the Anisakis spp. The prevalence of
      antibodies to T. gondii and T. canis was lower in subjects aged 1 to 9 years than
      in older subjects, probably because the persons in this group had less time to be
      infected. Antibody titers to A. cantonensis and the Anisakis spp. were high in
      the juvenile group, perhaps because recent changes in eating habits have
      increased opportunities for infection.

PMID- 9185270
TI  - Prevalence of intestinal parasitic infection among children in two villages in
      Lao PDR.
AB  - The prevalence of intestinal parasitic infection among 128 children under 15
      years old in two villages in Khammouane Province, southeastern Lao PDR, was
      investigated. Overall prevalence of helminth infection was 77.3%; the prevalence
      was 64.8% in children under 6 years, 88.5% in those aged 6-10 years and 81.8% in
      the age group above 11 years. The prevalent helminths found in the subjects were
      Ascaris lumbricoides (48.4%), Trichuris trichiura (43.8%), hookworm (37.5%) and
      Opisthorchis viverrini (37.5%). Intestinal protozoan infection was demonstrated
      in 14.1%; Giardia lamblia was the most prevalent (8.6%) protozoan species.

PMID- 9185271
TI  - Comparison of adult somatic and excretory-secretory antigens in enzyme-linked
      immunosorbent assay for serodiagnosis of human infection with Fasciola gigantica.
AB  - Adult somatic antigen extract of Fasciola gigantica was compared with excretory
      secretory (ES) antigen in an enzyme-linked immunosorbent assay (ELISA) for
      serodiagnosis of human fascioliasis gigantica. The absorbance values in ELISA
      using the adult somatic antigen were not significantly different from the values
      obtaining using ES antigen (p > 0.05). The diagnostic sensitivity, specificity
      and positive and negative predictive values of the test using adult somatic
      extract as antigen were 100%, 98%, 70% and 100%, respectively. On the other hand,
      these values of the test using adult ES antigen were 100%, 99.3%, 87.5% and 100%,
      respectively. It appears that both somatic and ES antigens are effective antigens
      for use in the serodiagnosis of human fascioliasis gigantica.

PMID- 9185272
TI  - Immunohistochemical localization of Gnathostoma spinigerum larval antigens by
      monoclonal antibodies: II. Electron microscopy.
AB  - Immunocytochemical localization of antigens in advanced third-stage larvae of
      Gnathostoma spinigerum (GsAL3) was studied by immunogold labeling method using
      seven G. spinigerum specific monoclonal antibodies (MAbs), FS-3D11, SS-5H5, SK
      6C4, SK-4E1, SK-7G6, SK-8D4 and SA-9B5. All these MAbs belong to the IgG1
      subclass and only FS-3D11 and SS-5H5 recognize carbohydrate epitopes. The
      paraformaldehyde-fixed GsAL3 were embedded in Lowicryl K4M medium, and the gold
      colloidal particles used were 15 nm in size. When the worm sections were probed
      with FS-3D11, the gold particles appeared to concentrate specifically on the
      intestinal brush border. When SS-5H5 was applied, the particles were scattered
      densely over the brush border and in the cytoplasm of epithelial cells. The rest
      of the MAbs which recognize protein determinants exhibited a lack of labeling.
      The results suggested that the carbohydrate antigenic determinants recognized by
      the two MAbs are the most stable and most abundant particularly in the intestine
      of GsAL3. These results also confirmed the previous finding that the most
      antigenic site of GsAL3 is the intestine.

PMID- 9185273
TI  - Outbreaks of cholera in Nepal.
AB  - This paper presents the study of the etiological agents of diarrhea in children
      below 14 years of age, this study was conducted from May 1995 to April 1996. One
      thousand one hundred seven (1,107) children with acute diarrhea receiving Oral
      Rehydration Therapy (ORT) at National Kanti Children's Hospital were included in
      this study. Stool samples of these patients were investigated at the Microbiology
      Laboratory, Department of Microbiology, Institute of Medicine. None of the stool
      samples showed the growth of Vibrio cholerae 0139 synonym Bengal. In Nepal,
      V.cholerae could be isolated from June to November. From December to May, no
      cases of V. cholerae were detected. Therefore, we address to this incidence as
      outbreaks rather than endemic. Mixed infections along with V. cholerae were also
      seen in 29% of cholera patients. V. cholerae 01, Hikojima types were the major
      isolates in our study followed by Ogawa type. V. cholerae, Hikojima and Ogawa
      serotypes were associated with mixed infection in 16.1% and 12.9% of patients,
      respectively. These isolates were associated with Shigella, Salmonella and
      pathogenic E. coli.

PMID- 9185274
TI  - Diagnosis of scrub typhus in Malaysian aborigines using nested polymerase chain
      reaction.
AB  - A rapid diagnostic system for scrub typhus using nested polymerase chain reaction
      (PCR) was applied to clinical samples from Malaysian Aborigines. Whole blood from
      twenty-four patients suspected of scrub typhus infection were tested using nested
      polymerase chain reaction and sera were evaluated by the indirect
      immunoperoxidase test. Antibody responses towards Rickettsia tsutsugamushi were
      observed in seventeen patients with the majority having high titers of IgG
      antibodies. Seven patients were seronegative. The nested PCR amplified R.
      tsutsugamushi DNA from six patients, of which two were negative serologically and
      four had high titers of IgG antibodies. Second samples collected seven days after
      treatment were negative by PCR testing. Nested PCR is highly sensitive and
      specific and may be used to provide rapid confirmation of scrub typhus cases in
      endemic region.

PMID- 9185275
TI  - Affinity and response of Burkholderia pseudomallei and Burkholderia cepacia to
      insulin.
AB  - The cells of Burkholderia pseudomallei, B. cepacia and Pseudomonas aeruginosa
      grown on agar plates were stained with fluorescently-labeled insulin. The former
      two species were stained positively indicating insulin binding but P. aeruginosa
      was not. Insulin exposure reduced phospholipase C and acid phosphatase activities
      of B. pseudomallei but did not affect those enzymatic activities of B. cepacia in
      the employed experimental conditions. It is suggested that B. pseudomallei have
      insulin receptors which may be associated with a signal transfer system involving
      phospholipase and protein tyrosine phosphatase.

PMID- 9185276
TI  - Evolution of cell-surface acid phosphatase of Burkholderia pseudomallei.
AB  - Acid phosphatase active fractions were obtained from cell-free extract,
      outermembrane fraction and culture filtrate of Burkholderia pseudomallei by
      column chromatography with sepharose 6B and DEAE cellulose. The comparison of the
      elution patterns of protein, sugar and enzymatic activity among these three
      components suggested that the enzyme is a glycoprotein evolving from premature
      proteins through glycosylation and that the enzyme is translocated during
      glycosylation from the cytoplasm to the outer membrane and finally excreted into
      the environment. When tunicamycin, a glycosylation inhibitor, was added to the
      culture, the peaks of sugar and enzymatic activity were lowered concomitantly
      leaving the protein peak unchanged in the elution pattern of the culture
      filtrate. The affinity of the bacterial surface to antienzyme sera was
      demonstrated by immuno-fluorescence microscopy.

PMID- 9185278
TI  - Antibacterial activity of teicoplanin against Clostridium difficile.
AB  - The in vitro inhibitory action of teicoplanin, vancomycin, metronidazole and
      clindamycin against clinical isolates of Clostridium difficile was investigated.
      Minimum inhibitory concentrations (MICs) were determined using E test.
      Teicoplanin (MIC range 0.023-0.75 microgram/ml), vancomycin (MIC range 0.5-3
      micrograms/ml) and metronidazole (MIC range 0.19-1 microgram/ml) were all very
      active against the isolates examined. No resistant strains of C. difficile to
      those three antimicrobial agents were observed, whereas resistance to clindamycin
      was found in 39.5% of the tested strains. Teicoplanin was about 4-times more
      potent than vancomycin. It appears to be a more promising antimicrobial for
      treatment of C. difficile enteric disease.

PMID- 9185277
TI  - Neonatal septic arthritis.
AB  - Neonatal septic arthritis has always been considered as separate from its
      counterpart in older children. The condition is uncommon but serious. Affected
      neonates usually survive, but with permanent skeletal deformities. Ten cases of
      neonatal septic arthritis were diagnosed between January 1989 and December 1993
      in the neonatal intensive care units of two referral hospitals in the state of
      Kelantan, Malaysia. All except one neonate was born prematurely. The mean age of
      presentation was 15.6 days. Joint swelling (10/10), increased warmth (7/10) and
      erythema of the overlying skin (7/10) were the common presenting signs. Vague
      constitutional symptoms preceded the definitive signs of septic arthritis in all
      cases. The total white cell counts were raised with shift to the left. The knee
      (60%) was not commonly affected, followed by the hip (13%) and ankle (13%). Three
      neonates had multiple joint involvement. Coexistence of arthritis with
      osteomyelitis was observed in seven neonates. The commonest organism isolated was
      methicillin resistant Staphylococcus aureus (9/10). Needle aspiration was
      performed in nine neonates and one had incision with drainage. Follow up data was
      available for five neonates and two of these had skeletal morbidity. Early
      diagnosis by frequent examination of the joints, prompt treatment and control of
      nosocomial infection are important for management.

PMID- 9185279
TI  - The effect of pyrethroid impregnated mosquito nets on field malaria vector
      populations in experimental huts and in individual local houses.
AB  - Studies were carried out in Tak Province, northwest Thailand to determine
      repellency and killing effects of four commercially available pyrethroids
      etofenprox, deltamethrin, lambdacyhalothrin and permethrin treated mosquito nets
      on field malaria vector populations in experimental huts and local houses. The
      studies reveal that all four test pyrethroids have a highly repellency effect.
      Repellency ratio between lifted and torn nets also showed some different among
      the four pyrethroids. Mosquito net treated with 0.3 g/m2 permethrin was most
      toxic to mosquito followed by 0.02 g/m2 deltamathrin, etofenprox 0.3 g/m2 and
      0.02 g/m2 lambdacyhalothrin. However, careful consideration for future use should
      also include problem of cross-resistance, persistence of chemicals and also type
      of mosquito net material.

PMID- 9185280
TI  - Insecticide impregnated cotton fabrics of different hydrophobicity against Aedes
      aegypti (Diptera:Culicidae).
AB  - Residual efficacy of synthetic pyrethroids, viz, permethrin, deltamethrin,
      lambdacyhalothrin and an insect repellent DEPA in cotton fabrics of different
      hydrophobicity was tested against Aedes aegypti. Amino silicone was used for
      enhancing the hydrophobicity of the fabrics. The results showed that there was an
      increasing trend in repellency/feeding deterrency with the increase in
      hydrophobicity up to 17.5 weeks at an optimum level of 30g/l. The adulticidal
      effect lasted for 1 to 4 weeks and this lower residual activity was attributed to
      the repellency of the treated fabrics. The results indicated that the residual
      efficacy of cotton fabrics could be enhanced by treating with an hydrophobic
      agent that increases the availability of the insecticide on the surface.

PMID- 9185281
TI  - Efficacy of Bacillus sphaericus in different breeding habitats of Culex
      quinquefasciatus.
AB  - 'Spherifix', an alginate based slow release formulation of Bacillus sphaericus
      was field tested in different types of breeding habitats of Culex
      quinquefasciatus at the dose of 15 kg ai/ha at bimonthly interval. The efficacy
      of the formulation was higher in most of the months except in rainy and post
      rainy months. The mean percentage reduction +/-SD during the treatment phase of
      one year was 31.2 +/- 17.9, 50 +/- 29.4, 28.3 +/- 17.6, 30.3 +/- 21.1, 66 +/-
      22.5 and 53 +/- 20.4 in larval density and 49 +/- 20.8, 65.1 +/- 26.1, 30.3 +/-
      21.9, 59.8 +/- 22.6, 63.1 +/- 21.9 and 47.7 +/- 24.2 in pupal density
      respectively in cement tanks, cesspools, cesspits, disused wells, unlined drains
      and cement lined drains. The reduction in immature density was relatively higher
      in undisturbed, debris free and shallow habitats such as cesspools, unlined
      drains and cement lined drains. After withdrawal of treatment, the effect of the
      formulation could be seen for a period of four months.

PMID- 9185282
TI  - Microdroplet application of mosquitocidal Bacillus thuringiensis using ultra-low
      volume generator for the control of mosquitos.
AB  - In an effort to develop a more effective technique in dispersing a microbial
      control agent, Bacillus thuringiensis (Bt), a truck-mounted ultra low volume
      (ULV) generator (Scorpion) was used to disperse B. thuringiensis israelensis
      (Bti) and Bti with malathion. Complete larval and adult mortalities for all
      tested mosquito species within the first 70-80 feet from the ULV generator were
      achieved. Beyond that distance less than 50% mortality was achieved as
      insufficient sprayed particles reached the area. A minimum of 10(3) Bti colony
      forming units per ml is required to cause 100% larval mortality. The sprayed Bti
      larvicidal toxins were persistent in the test water 7 days post ULV. The
      effectiveness of B. thuringiensis jegathesan (Btj), a new mosquitocidal Bt
      serotype was also evaluated. Similar mortality results as Bti were achieved
      except that the Btj toxins underwent degradation in the test water, since less
      than 50% less in larval mortality was observed in 7 days post ULV samples. This
      ULV method has the potential to disperse Bt and malathion effectively for a
      simultaneous control of mosquito adults and larvae.

PMID- 9185283
TI  - The biology and predatory potential of notonectid bug, Enithares indica (Fabr)
      against mosquito larvae.
AB  - The biology of a notonectid bug Enithares indica against immatures of Anopheline,
      Culicine and Aedine mosquitos was studied in the laboratory. The life cycle of
      the bug consists of the egg and five nymphal stages and takes about 64 +/- 1.54
      days for completion. All stages of E. indica have good predatory potential. It
      can be used as a biological control agent in an integrated disease vector control
      program.

PMID- 9185284
TI  - Anopheles donaldi incriminated as a vector of periodic Brugia malayi in Grik,
      Perak, Malaysia.
AB  - Studies were carried out to observe the species composition of mosquitos and to
      determine the vectors responsible for the transmission of filariasis in Grik,
      Perak, Malaysia. A total of 2,155 mosquitos belonging to 7 genera and 30 species
      were collected. Anopheles donaldi comprised 24.1% of the collection. Twelve out
      of 519 An. donaldi were infected with L3 larvae of Brugia malayi. The peak biting
      time was around 23.00-24.00 hours. The infective bites per month ranged from 0 to
      6.3.

PMID- 9185285
TI  - Use of hemolymph test for detection of rickettsiae in Malaysian ticks.

PMID- 9185286
TI  - The impact of the EM algorithm on medical statistics.

PMID- 9185287
TI  - The EM algorithm and medical studies: a historical link.
AB  - Anderson Gray McKendrick's 1926 paper, 'Applications of mathematics to medical
      problems', was the earliest reference cited in Dempster et al.'s 1977 paper that
      defined and popularized the EM algorithm. McKendrick's paper was prominently
      featured by Joseph Oscar Irwin in his 1962 inaugural address as the President of
      the Royal Statistical Society (in the UK), entitled 'The place of mathematics in
      medical and biological statistics'. The link of McKendrick's work to the EM
      algorithm is due to an improvement made by Irwin on a novel method McKendrick
      used for estimating an infection rate when the observed data do not distinguish
      between those individuals who are not susceptible to the infection and those who
      are susceptible, but do not develop symptoms. This article examines this link,
      along the way illustrating the central ideas underlying the EM algorithm as well
      as its properties; the examination also suggests a profiling strategy for
      speeding up EM, which may be worthy of general investigation. McKendrick's data
      on an epidemic of cholera are used for illustration and to compare EM with
      Irwin's method as well as the Newton-Raphson algorithm. Issues beyond computation
      are also discussed whenever appropriate.

PMID- 9185288
TI  - Uses of the EM algorithm in the analysis of data on HIV/AIDS and other infectious
      diseases.
AB  - The analysis of data on infectious diseases is a natural setting for applications
      of the EM algorithm, because the infection process is only partially observable.
      Difficulties in determining the expectation at the E step have been side-stepped
      by adopting pragmatic models which reflect only part of the mechanism that
      generates the data. In the HIV/AIDS context the EM algorithm has helped in the
      reconstruction of the unobserved HIV infection curve, the so-called
      backprojection problem, as well as in the estimation of the distribution for the
      incubation period until AIDS, in estimating the infectivity of HIV in
      partnerships and in estimating parameters describing the decline in the immune
      system. There is a need for smooth estimates of functions in these applications,
      suggesting the use of the EMS algorithm or use of the EM algorithm to maximize a
      penalized likelihood. For data on other infectious diseases the application of
      the EM algorithm has so far been restricted to analyses of data on the size of
      outbreaks in a sample of households.

PMID- 9185289
TI  - EM algorithms without missing data.
AB  - Most problems in computational statistics involve optimization of an objective
      function such as a loglikelihood, a sum of squares, or a log posterior function.
      The EM algorithm is one of the most effective algorithms for maximization because
      it iteratively transfers maximization from a complex function to a simple,
      surrogate function. This theoretical perspective clarifies the operation of the
      EM algorithm and suggests novel generalizations. Besides simplifying
      maximization, optimization transfer usually leads to highly stable algorithms
      with well-understood local and global convergence properties. Although
      convergence can be excruciatingly slow, various devices exist for accelerating
      it. Beginning with the EM algorithm, we review in this paper several optimization
      transfer algorithms of substantial utility in medical statistics.

PMID- 9185290
TI  - The EM algorithm in medical imaging.
AB  - This article outlines the statistical developments that have taken place in the
      use of the EM algorithm in emission and transmission tomography during the past
      decade or so. We discuss the statistical aspects of the modelling of the
      projection data for both the emission and transmission cases and define the
      relevant probability models. This leads to the use of the method of maximum
      likelihood as a means of estimating the relevant unknown parameters within a
      given region of a patient's body and to the use of the EM algorithm to compute
      the reconstruction. Various different types of EM algorithm are discussed,
      including the SAGE algorithms of Fessler and Hero. The limitations of the EM
      algorithm, per se, are covered and the need for regularization is stressed. A
      number of different methods for penalizing the likelihood are described and a
      number of algorithms for the computation of the penalized EM reconstruction are
      discussed.

PMID- 9185291
TI  - On the EM algorithm for overdispersed count data.
AB  - In this paper, we consider the use of the EM algorithm for the fitting of
      distributions by maximum likelihood to overdispersed count data. In the course of
      this, we also provide a review of various approaches that have been proposed for
      the analysis of such data. As the Poisson and binomial regression models, which
      are often adopted in the first instance for these analyses, are particular
      examples of a generalized linear model (GLM), the focus of the account is on the
      modifications and extensions to GLMs for the handling of overdispersed count
      data.

PMID- 9185292
TI  - Comparative studies on omega-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha,
      12 alpha-triol in the mitochondrial and microsomal fraction of the liver from
      several vertebrates.
AB  - The activity and the stereospecificity of omega-hydroxylation, a hydroxylation at
      one of the two terminal methyl groups of 5 beta-cholestane-3 alpha, 7 alpha, 12
      alpha-triol, which is thought to be the first step in side-chain degradation
      resulting in the formation of cholic acid, was elucidated in mitochondria and
      microsomes of the liver from several evolutionarily primitive vertebrates, fish,
      frogs, turtles, and chickens in addition to such mammals as rats. hamsters, and
      rabbits. The detection of omega-hydroxylation products (25R)- and (25S)-5 beta
      cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrols as well as the separation of
      their two isomers was facilitated using high-performance liquid chromatography
      after conversion to 9-anthroyl derivatives. All the mammals examined, except for
      the rat, exhibited predominant activity in the mitochondrial fraction. Although
      the hydroxylation activity was somewhat lower in the primitive vertebrates, it
      was present in the mitochondria more than in the microsomes. Furthermore, the
      stereospecific formation of a 25R-isomer was detected in the mitochondrial
      fraction of most animals estimated. However, activity in the carp liver was seven
      times higher in the microsomes than in the mitochondria, and the hydroxylation
      product was almost always a 25R-isomer. Omega-Hydroxylation activity could not be
      detected in rainbow trout, suggesting the existence of another biosynthetic
      pathway, not via 26-hydroxylation, as in the 25-hydroxylation pathway, for the
      production of bile acid.

PMID- 9185293
TI  - An efficient stereoselective synthesis of 6-alpha-aminoestradiol: preparation of
      estradiol fluorescent probes.
AB  - 6-Oxoestradiol (2) was protected as its bis[(2-trimethylsilylethoxy)methyl] ether
      (4) and converted to the corresponding oxime (4). The oxime (4) on reduction with
      zinc in ethanol afforded the bis-SEM ether of 6-alpha-aminoestradiol (5) in 96%
      epimeric excess. Subsequently, 5 was hydrolyzed with HF to 6-alpha-aminoestradiol
      (6) in good yield. The absolute stereochemistry of the amino group in 6 was
      established by NMR and confirmed by X-ray crystallography on the corresponding 4
      bromobenzamide derivative (9). Treatment of amine (6) with 6-(t
      butoxycarbonylamino)hexanoic acid succinimidyl ester (10) followed by hydrolysis
      produced the amine (12) with a C-6 linker. The fluorescent probes (7 and 13) were
      prepared from 6 and 12 respectively, in 54-60% yield and > 99% purity.

PMID- 9185294
TI  - Synthesis of novel 21-trifluoropregnane steroids: inhibitors of 17 alpha
      hydroxylase/17,20-lyase (17 alpha-lyase).
AB  - Novel 21-trifluoropregnenolone (6), 21-trifluoroprogesterone (7) and related
      compounds 4a and 8 have been synthesized in high yields from 3 beta
      acetoxyandrost-5-ene-17 beta-carbaldehyde (3). The key reaction was the
      conversion of 3 into the 21-trifluoromethyl-20-alcohol as a diastereomeric
      mixture (4) by trifluoromethyltrimethylsilane (TMS-CF3) in the presence of
      tetrabutylammonium fluoride (TBAF). All compounds, including 6 and 7, were
      unambiguously characterized by IR, 1H and 19F NMR, high-resolution mass
      spectrometry (HRMS), and elemental analysis. On this basis, we concluded that the
      only report of an earlier synthesis of 6 and 7 is erroneous. Enzyme inhibition
      studies showed that 20 xi-hydroxy-21-trifluoropregn-4-en-3-one (8) is a potent
      inhibitor (IC50 value = 0.6 microM) of rat 17 alpha-hydroxylase/17,20-lyase.

PMID- 9185295
TI  - Effect of the hydroxyl group on the oxidative cleavage (beta-oxidation) of
      steroidal side chain for bile acid biosynthesis in rat liver homogenate.
AB  - Mono-, di-, tri-, and tetrahydroxy-5 beta-cholestan-26-oic acids were incubated
      with rat liver homogenate (800 x g supernatant and light mitochondrial fraction)
      to study substrate specificity in the side-chain cleavage reaction (beta
      oxidation) of bile acid biosynthesis. The C27-intermediates (5 beta-cholest-24-en
      26-oic acids and 24-hydroxy-5 beta-cholestan-26-oic acids) in beta-oxidation and
      the corresponding C24-bile acids were quantitatively determined by capillary gas
      chromatography. Monohydroxy-5 beta-cholestan-26-oic acid was not converted into
      C24-bile acid. Di- and trihydroxy-5 beta-cholestan-26-oic acids were effectively
      transformed into the C27-intermediates and C24-bile acids. Tetrahydroxy-5 beta
      cholestan-26-oic acids were also converted into C27-intermediates and
      corresponding C24-bile acids. The intermediate 24-hydroxy-5 beta-cholestan-26-oic
      acids could not be detected in the products by incubation with the light
      mitochondrial fraction. The total specific activity of protein in the light
      mitochondrial fraction for the production of C27-intermediates and C24-bile acids
      was higher than that of 800 x g supernatant solution. The effects of the number
      and the position of hydroxyl groups on the side-chain degradation are discussed.

PMID- 9185296
TI  - A direct stereoselective synthesis of 7 beta-hydroxytestosterone.
AB  - Although 7 beta-hydroxytestosterone is a known product of hepatic androgen
      metabolism, there are no published methods for its chemical synthesis except from
      the equally difficult to obtain 7 beta-hydroxy-4-androstene-3,17-dione. We found
      that several seemingly straightforward routes for its synthesis failed.
      Consequently, we tried to produce 7 beta-hydroxytestosterone by enzymatic
      oxidation of 5-androstene-3 beta, 7 beta, 17 beta-triol with cholesterol oxidase
      (Brevibacterium sp.), a procedure previously used to synthesize 7 beta-hydroxy-4
      cholesten-3-one from 3 beta, 7 beta-dihydroxycholesterol (Alexander and Fisher
      1995). However, 5-androstene-3 beta, 7 beta, 17 beta-triol was, at best, a very
      poor substrate for the enzyme leading to the production of 7 beta
      hydroxytestosterone in only trace amounts. Thus, we explored a strategy for the
      enzymatic synthesis in which a C8-ester at C-17 (5-androstene-3 beta, 7 beta, 17
      beta-triol 17-caprylate) would serve to mimic the bulky and hydrophobic side
      chain of cholesterol and thus allow the C19-steroid to act as an effective
      substrate. When this ester was incubated with cholesterol oxidase, it was
      converted efficiently to 7 beta-hydroxytestosterone-17-caprylate. Attempts to
      remove the ester group by several mild hydrolytic procedures caused elimination
      of the 7 beta-hydroxyl group; we, therefore, obtained 7 beta-hydroxytestosterone
      by incubation of the intermediate ester with porcine lipase.

PMID- 9185297
TI  - New synthesis of delta 6-estrogens.
AB  - An efficient approach to synthesize delta 6-estrogens is described. The key steps
      in the synthesis are the introduction of a hydroxyl group at the C-6 position of
      a suitably protected estrogen using a superbase and subsequent dehydration with
      Martin sulfurane reagent or methyltriphenoxyphosphonium iodide. The two-step
      synthetic procedure readily gave the delta 6-estrogens in high yield.

PMID- 9185298
TI  - New steroidal anti-inflammatory antedrugs: methyl 3,20-dioxo-9 alpha-fluoro-11
      beta,17 alpha,21-trihydroxy-1,4-pregnadiene-16 alpha-carboxylate and methyl 21
      acetyloxy-3,20-dioxo-11 beta, 17 alpha-dihydroxy-9 alpha-fluoro-1,4-pregnadiene
      16 alpha-carboxylate.
AB  - Focused efforts have been made to increase local-to-systemic activity ratios of
      potent anti-inflammatory steroids for local and/or topical applications. The
      approach taken in the present investigation is based upon the concept of
      "antedrug," defined as a locally active compound that exerts its action at the
      application site but rapidly undergoes a predictable biotransformation to an
      inactive metabolite that is readily excreted upon entry into the systemic
      circulation. In continuing efforts to synthesize potent, anti-inflammatory
      steroids without systemic glucocorticoid activities, 9 alpha-fluoro-methyl 11
      beta, 17 alpha, 21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate
      (FP16CM) and its 21-acetate derivative (FP16CMAc) have been synthesized and
      screened. Novel antedrugs were evaluated for antiinflammatory activity in the
      acute croton oil-induced ear edema bioassay, adverse systemic effects in the 5
      day croton oil model, receptor binding, and concomitant L-tyrosine-2-oxoglutarate
      aminotransferase (EC 2.6.1.5) (TAT) enzyme induction in HTC cells in culture.
      Following a single topical application in the croton oil-induced ear edema
      bioassay, treatment with all compounds resulted in dose-dependent inhibition of
      edema. From these dose-response profiles, the following ID50 values (nmol
      resulting in a 50% reduction of edema) were calculated: 817, 540, 266, and 67 for
      hydrocortisone (HC), prednisolone (P), FP16CM, and FP16CMAc, respectively.
      Calculated relative potencies, setting HC = 1.0, were P, 1.5; FP16CM, 3.1, and
      FP16CMAc, 12.2. Results of the 5-day rat croton oil ear edema bioassay indicated
      that, in contrast to the parent compound P, the novel steroidal antedrugs did not
      significantly alter body weight gain, thymus weights, or plasma corticosterone
      levels. Relative binding potencies for cytosolic HTC glucocorticoid receptors
      were 1.0, 20.1, 5.4, and 2.5 for HC, P, FP16CM, and FP16CMAc, respectively. As
      predicted by the antedrug concept, FP16CM and FP16CMAc were very weak agonists
      for induction of TAT in HTC cells. Collectively, results of these investigations
      suggest that modification of P, which included addition of the 9-fluoro and 16
      methoxycarbonyl group alone or in conjunction with a 21-acetoxy moiety, increase
      topical anti-inflammatory activity without significant adverse systemic effects.
      These new antedrugs may be useful as anti-inflammatory steroids for local
      applications.

PMID- 9185299
TI  - Allylic nitration of 3 beta-sitosterol and cholesterol acetate: preparation of 7
      nitro derivatives.

PMID- 9185300
TI  - A practical route for the synthesis of 17 substituted steroidal 3-thioxamides.
AB  - A facile method for the synthesis of a series of new steroidal 3-thioxamides from
      the 3-oxo compound, variously substituted at the 17 position, is described. The
      "one pot" reaction, using Lawesson's reagent (4-methoxyphenylthionophosphine
      sulphide dimer) in dichloromethane solution, gives the desired compounds with a
      high degree of chemoselectivity, in good yields (> 80%).

PMID- 9185301
TI  - Inadequate frameworks for understanding bodily homeostasis.
AB  - Separate nervous systems, somatic and autonomic, were proposed to regulate the
      portion of the individual's life that is concerned with the external environment
      and the portion that is concerned with internal homeostasis. Regulation of the
      autonomic system by the CNS was assigned to the limbic system. Brainstem
      circuitry, between limbic and autonomic systems, was assigned to the supposedly
      nonspecific reticular formation. In fact, daily survival depends on integrated
      control of behavior and internal physiology. In mammals only the brain has the
      inbuilt programming for patterned co-ordination of these activities. The terms
      autonomic nervous system, limbic system and reticular formation are at odds with
      this patterned co-ordination. They should be abandoned and replaced with the term
      visceral neurons (afferent and efferent) and with reference to relevant specific
      neural circuitry in the brain.

PMID- 9185302
TI  - Alexander von Humboldt and the concept of animal electricity.
AB  - More than two hundred years ago, Alexander von Humboldt helped to establish
      Galvani's view that muscle and nerve tissue are electrically excitable. His 1797
      publication was a landmark for establishing the concept of animal electricity.
      Almost half a century later, von Humboldt became the mentor of the young du Bois
      Reymond. With the help of von Humboldt's promotion, du Bois-Reymond demonstrated
      convincingly that animal tissue has the intrinsic capacity to generate electrical
      activity, and thus laid the ground for modern electrophysiology.

PMID- 9185303
TI  - Does r-EAG contribute to the M-current?

PMID- 9185304
TI  - 5-HT neurones--bursting with information?

PMID- 9185305
TI  - The neural basis of associative reward learning in honeybees.
AB  - Appetitive learning of food-predicting stimuli, an essential part of foraging
      behavior in honeybees, follows the rules of associative learning. In the learning
      of odors as reward-predicting stimuli, an individual neuron, one of a small group
      of large ascending neurons that serve principal brain neuropiles, mediates the
      reward and has experience-dependent response properties. This implies that this
      neuron functions as an integral part of associative memory, might underlie more
      complex features of learning, and could participate in the implementation of
      learning rules. Moreover, its structural properties suggest that it organizes the
      interaction of functionally different neural nets during learning and experience
      dependent behavior.

PMID- 9185306
TI  - NF-kappa B: a crucial transcription factor for glial and neuronal cell function.
AB  - Transcription factors provide the link between early membrane-proximal signalling
      events and changes in gene expression. NF-kappa B is one of the best
      characterized transcription factors. It is expressed ubiquitously and regulates
      the expression of many genes, most of which encode proteins that play an
      important and often determining role in the processes of immunity and
      inflammation. Apart from its role in these events, evidence has begun to
      accumulate that NF-kappa B is involved in brain function, particularly following
      injury and in neurodegenerative conditions such as Alzheimer's disease. NF-kappa
      B might also be important for viral replication in the CNS. An involvement of NF
      kappa B in neuronal development is suggested from studies that demonstrate its
      activation in neurones in certain regions of the brain during neurogenesis. Brain
      specific activators of NF-kappa B include glutamate (via both AMPA/KA and NMDA
      receptors) and neurotrophins, pointing to an involvement in synaptic plasticity.
      NF-kappa B can therefore be considered as one of the most important transcription
      factors characterized in brain to date and it might be as crucial for neuronal
      and glial cell function as it is for immune cells.

PMID- 9185307
TI  - Building a brain: developmental insights in insects.
AB  - Understanding the cellular, molecular and genetic mechanisms involved in building
      the brain remains one of the most challenging problems of neurobiology. In this
      article, we review recent work on the developmental mechanisms that generate the
      embryonic brain in insects. We compare some of the early developmental events
      that occur in the insect brain with those that operate during brain development
      in vertebrates and find that numerous parallels are present at both the cellular
      and the molecular levels. Thus, the roles of glial cells in prefiguring axon
      pathways, the function of pioneer neurons in establishing axon pathways, and the
      formation of a primary axon scaffolding are features of embryonic brain
      development in both insects and vertebrates. Moreover, at the molecular genetic
      level homologous regulatory genes control morphogenesis, regionalization and
      patterning during embryonic brain development in both insects and vertebrates.
      This indicates that there might be universal mechanisms for brain development,
      and that knowledge gained from Drosophila and other insects is relevant to our
      understanding of brain development in other more complex organisms, including
      man.

PMID- 9185308
TI  - The postsynaptic density at glutamatergic synapses.
AB  - The postsynaptic density (PSD) is a tiny, amorphous structure located beneath the
      postsynaptic membrane of synapses in the CNS. Until recently, the molecular
      composition and function of the PSD were mostly matters of speculation. With the
      advent of powerful new microchemical tools and molecular-genetic methods, three
      new classes of proteins have been identified in the PSD at glutamatergic
      synapses: the PSD-95 family, the NR2B subunit of the NMDA-type glutamate
      receptor, and densin-180. The PSD-95 family is involved in clustering of NMDA
      receptors. NR2B is phosphorylated by Ca2(+)-calmodulin-dependent protein kinase
      type II, a prominent constituent of the PSD. Densin-180 might represent a new
      class of synaptic adhesion molecule. Study of these molecules is beginning to
      reveal the functional significance of the PSD.

PMID- 9185309
TI  - New evidence for neurotransmitter influences on brain development.
AB  - The early appearance of monoamine systems in the developing mammalian CNS
      suggests that they play a role in neural development. We review data from two
      model systems that provide compelling new evidence of this role. In one model
      system-in utero exposure to cocaine-specific and robust alterations are seen in
      dopamine-rich areas of the cerebral cortex, such as the anterior cingulate
      cortex: D1 receptor-G protein coupling is greatly reduced, the GABAergic system
      is altered and pyramidal dendrites undergo excessive growth. In a second model
      system-a transgenic mouse line in which the gene that encodes monoamine oxidase A
      (MAOA) is disrupted, resulting in excessively high 5-HT levels-barrels fail to
      form in the developing somatosensory cortex. Both models reveal the effects of
      very early manipulation of monoamines on forebrain development, and the long-term
      anomalies that persist into adulthood.

PMID- 9185310
TI  - Medetomidine as a premedicant for ketamine, propofol or fentanyl anaesthesia in
      dogs.
AB  - This study evaluated the quality of anaesthesia and the cardiorespiratory effects
      induced by the combination of medetomidine with either ketamine, propofol or
      fentanyl. Medetomidine premedication (1000 or 1500 micrograms/m2 body surface
      area) was followed by intravenous induction of anaesthesia with ketamine (3.0
      mg/kg), propofol (2.0 mg/kg) or fentanyl (2.0 micrograms/kg) in bitches
      undergoing elective ovariohysterectomy. Anaesthesia was prolonged by incremental
      doses of the induction agents as necessary. The mean (sem) overall doses
      (including induction) were 0.09 (0.01) mg/kg/min for ketamine, 0.06 (0.01)
      mg/kg/min for propofol and 0.07 (0.005) microgram/kg/min for fentanyl during
      procedures which lasted 88 (6) minutes, 72 (3) minutes and 79 (7) minutes,
      respectively. At the end of the procedure, medetomidine was antagonised with
      atipamezole. The quality of anaesthesia, heart rate and arterial blood pressure
      were recorded continuously and arterial blood gases were measured at intervals.
      At the end of the procedure, the animals received 10 micrograms/kg buprenorphine
      intramuscularly for postoperative analgesia. From the adequacy of anaesthesia,
      the lack of significant adverse side effects and the reliable and rapid recovery
      it is concluded that, in healthy dogs anaesthetised with ketamine or propofol,
      medetomidine is a satisfactory sedative-analgesic premedicant. The differences in
      haemodynamics and the quality of recovery suggest that the combination of
      medetomidine with propofol provided the better quality anaesthesia. The
      combination of medetomidine with fentanyl was unsuitable for obtaining surgical
      anaesthesia in spontaneously breathing animals owing to the severity of the
      respiratory depression at dosages needed for general anaesthesia.

PMID- 9185311
TI  - Poisoning of dairy heifers by mercurous chloride.
AB  - Mercury poisoning was diagnosed in four dairy heifers, three of which died. The
      clinical signs were variable and included salivation, excessive thirst, extreme
      depression and severe diarrhoea. Postmortem examinations revealed inflammation
      and ulceration of the alimentary tract, pulmonary and cardiac haemorrhages,
      pallor of the kidney cortices and perirenal oedema. The kidney mercury
      concentrations were in the range 58 to 91 micrograms/g wet tissue. It is believed
      that the animals were poisoned by the ingestion of soil contaminated with
      mercurous chloride.

PMID- 9185312
TI  - Options for management of acute pain in the rat.
AB  - Clinical recommendations for analgesics in laboratory rodents are usually derived
      from basic research. However, animal models of pain often involve withdrawal
      reflexes evoked by threshold-level stimuli, whereas pain associated with surgery
      or disease involves injury and inflammation. Moreover, the analgesics used in
      research tend to be chosen as exemplars of a drug class, without regard for
      whether the route of administration is practical, whether the drug has useful
      kinetics or whether the side effects are tolerable. This paper provides data on
      the efficacy of drugs from four classes, using the formalin test as a model of
      injury-induced pain. Formalin (50 microliters, 2.5 per cent) was injected
      subcutaneously into a rat's paw and the behavioural response (lifting or licking
      of the paw) was recorded. Buprenorphine at 0.1 mg/kg and dipyrone at 200 mg/kg
      completely suppressed the pain responses. When formalin was injected six hours
      after buprenorphine or dipyrone, pain scores were 30 per cent of control scores.
      In the absence of pain and handling, 0.6 mg/kg buprenorphine was lethal to 25 per
      cent of rats. Locomotor activity was slightly depressed by 300 mg/kg dipyrone.
      Xylazine at 2 mg/kg suppressed pain responses, but the analgesia had decreased to
      less than 50 per cent after two hours and the effects were variable thereafter;
      at 8 mg/kg rats were unresponsive to a strong pinch. Acepromazine at 2.5 mg/kg
      reduced pain to 20 per cent of control scores and this level of analgesia was
      maintained for six hours; neuroleptic effects were prominent at 5 mg/kg.

PMID- 9185313
TI  - Serological diagnosis of toxoplasmosis in sheep following vaccination and
      challenge.

PMID- 9185314
TI  - 'Gut-tie' in a recently castrated steer.

PMID- 9185315
TI  - Posterior paralysis in a lamb caused by a Coeneurus cerebralis cyst in the lumbar
      spinal cord.

PMID- 9185316
TI  - Avermectin toxicity in the dog.

PMID- 9185317
TI  - Avermectin toxicity in the dog.

PMID- 9185318
TI  - Suspected allergic reaction to penicillamine in mute swans.

PMID- 9185319
TI  - Haematoma of the heel as a cause of lameness in dairy cattle.

PMID- 9185321
TI  - Moonstruck ostriches.

PMID- 9185320
TI  - Frozen tail or limber tail in working dogs.

PMID- 9185323
TI  - Impact of endosulfan on cytoplasmic and mitochondrial liver malate dehydrogenase
      from the freshwater catfish (Clarias batrachus).
AB  - The impact of a sublethal concentration of an organochlorine pesticide endosulfan
      on the activity, specific activity, electrophoretic patterns and kinetic
      properties of crude and purified forms of cytoplasmic malate dehydrogenase (cMDH)
      and mitochondrial malate dehydrogenase (mMDH) was evaluated in the liver of the
      freshwater catfish, Clarias batrachus. The endosulfan reduced significantly the
      activity and the specific activity of cMDH and mMDH, but had no effect on total
      cytoplasmic and mitochondrial protein contents. The inhibition produced by
      endosulfan was of mixed non-competitive-uncompetitive type (KiE > KiES) and of
      mixed competitive-non-competitive type (KiE < KiES) for crude cMDH and mMDH,
      respectively. The PAGE shows five distinct isoforms (C1 to C5) of cMDH and two
      isoforms (M1 and M2) of mMDH. The C5-isoform of liver cMDH is predominant and it
      corresponds to M2-isoform of mMDH. There are no endosulfan-associated differences
      in the relative charges of crude cMDH and mMDH as well as their purified
      isoforms, C5-cMDH and M2-mMDH. The relative molecular weights of the purified
      isoforms are not affected by endosulfan. The purified C5-cMDH and M2-mMDH of
      endosulfan-treated liver in vivo showed simple non-competitive (KiE = KiES) type
      of inhibition; whereas in vitro it was of uncompetitive (KiES) and mixed
      competitive-non-competitive (Ki < KiES) type for the two respective isoforms. G-1
      P acts as an uncompetitive (KiES) inhibitor of C5-cMDH and mixed competitive-non
      competitive (KiE < KiES) inhibitor of M2-mMDH of the control fish. The inhibitory
      pattern of G-1-P is modulated by endosulfan in case of C5-cMDH; whereas there is
      no alteration in case of M2-mMDH. Summarizing, it can be stated that endosulfan
      exerts an inhibitory effect on crude cMDH and mMDH in vivo, and their purified
      isoforms (C5-cMDH and M2-mMDH) in vivo as well as in vitro. The impact of
      endosulfan is mediated through enzyme-substrate-endosulfan (ES-END) complexing
      for cMDH and enzyme-endosulfan (E-END) complexing for mMDH.

PMID- 9185322
TI  - Weak organic acid uptake in rat renal tubules in vitro: stimulation by pent-4
      enoic acid.
AB  - A hypoglycemic agent, pent-4-enoic acid (4-PA; 0.1-1.0 mM), stimulated baseline
      uptake of a weak organic anion, fluorescein, in superficial proximal tubules of
      rat kidney and inhibited the rate of glucose production from pyruvate (but not
      lactate or endogenous substrates) by rat renal cortex fragment suspension. The
      stimulation of the fluorescein uptake was not observed in a low Na+ medium.
      Maleate (0.1-1.0 mM) and Cd2+ (0.1 mM), known similarly to 4-PA to induce the
      renal Fanconi syndrome, also stimulated the fluorescein uptake in the Na
      dependent manner. Both 4-PA and Cd2+ and maleate elevated intracellular content
      of alpha-ketoglutarate and increased ammonia formation from endogenous substrates
      in the suspension of the rat renal cortex fragments. The stimulatory effects of 4
      PA, maleate and Cd2+ on the fluorescein uptake were markedly attenuated by LiCl
      (5 mM), suggesting that the Na-coupled re-uptake of alpha-ketoglutarate is
      involved in energization of the fluorescein uptake in the exchange for the
      cytoplasmic dicarboxylate.

PMID- 9185324
TI  - Rabbit cerebral cortex 5HT1a receptors.
AB  - Selective 5HT1a agonist binding to membranes from rabbit cerebral cortex was
      concentration-dependent and saturable; the Kd was 1.1 nM and Bmax of 480 fmols/mg
      protein. Scatchard as well as Hill plots were linear; the Hill coefficient was
      0.96, suggesting a single, non-interacting binding site. Agonist binding was
      inhibited in a concentration-dependent fashion by gamma S GTP, a result
      consistent with the coupling of this binding site to the G protein signal
      transduction system. In competition experiments involving agonist and a series of
      agents with known affinities and specificities at 5HT1a receptors, a rank order
      relationship was found consistent with this binding site being a 5HT1a binding
      site. Direct comparisons of agonist and antagonist binding at rat cerebral cortex
      5HT1a receptors and cloned human 5HT1a receptors also suggested that the rabbit
      binding site belongs to the 5HT1a class. The only rank order anomalies were with
      methiothepin in rabbit cerebral cortex, where a comparatively high Ki was
      observed and with buspirone in cloned human 5HT1a receptor, where a low Ki was
      determined; these anomalies bear further study in light of the comparative
      pharmacology of 5HT1a receptors. Finally, the natural product parthenolide was
      tested for affinity in the rabbit, rat, and human systems, where it uniformly was
      unable to displace agonist, suggesting that the 5HT1a receptor is not a target
      for this compound. Overall, these results suggest that a functional 5HT1a
      receptor exists in rabbit cerebral cortex.

PMID- 9185325
TI  - Influence of follicular maturation on the susceptibility of chicken ovarian
      granulosa cells to free oxygen radicals.
AB  - The influence of ovarian follicular maturation on lipid peroxidation-induced
      changes in the fluidity of plasma membrane of granulosa cells was investigated
      using the fluorogenic polyunsaturated fatty acid cis-parinaric acid (cPNA). An
      increase in lipid peroxidation results in the decrease of fluorescence intensity
      of cPNA. A decrease in membrane fluidity results in the decrease of fluorescence
      polarization of cPNA. Granulosa cells isolated from the largest (F1; mature), and
      third largest (F3; developing) preovulatory follicles as well as from a pool of
      immature small yellow follicles (SYF) of the domestic hen ovary were pre-labelled
      with cPNA. The cPNA-labelled cells were exposed to a free oxygen radical
      generating agent 2,2'azobis-(2-amidinopropane)-hydrochloride (AAPH). AAPH
      enhanced the rate of decrease in fluorescence intensity of cPNA-labelled cells.
      This effect of AAPH was greater in the more differentiated granulosa cells
      obtained from mature follicles than in less differentiated cells isolated from
      immature follicles. Similarly, the degree of change in fluorescence polarization
      was greater in more differentiated F1 granulosa cells than in the less
      differentiated ones. The analysis of fatty acid composition of phospholipids
      indicated that the plasma membrane of differentiated granulosa cells contained a
      higher proportion of the unsaturated fatty acids, oleic and linoleic acids. The
      fluorescence data show that the rigidity of the plasma membrane of chicken
      granulosa cells decreases with advancing follicular maturation presumably due to
      relative increase in the unsaturated fatty acid content of plasma membrane
      phospholipid.

PMID- 9185326
TI  - Biological activities of aqueous extracts from marine sponges and cytotoxic
      effects of 3-alkylpyridinium polymers from Reniera sarai.
AB  - We screened the biological activity of 21 marine sponges collected in the
      northern Adriatic sea. Hemolytic, hemagglutinating, antimicrobial, cytotoxic, and
      anti-acetilcholinesterase activities of the extracts were monitored. We found
      that hemolytic activity was generally weak; only extracts from three sponge
      species possess considerable activity. Hemagglutinating activity was present in
      almost half of extracts but with little specificity against human erythrocytes of
      different blood groups. Detectable antimicrobial activity was present in only two
      extracts, while most of them possessed cytotoxic activity. Strong anti
      cholinesterase activity was present only in one sample. 3-alkypyridinium polymers
      isolated from Reniera sarai were hemolytic and strongly cytotoxic against
      different cell lines with slightly expressed specificity against transformed
      cells.

PMID- 9185328
TI  - Effect of exogenous cholecystokinin on the discharge of the gallbladder and the
      secretion of trypsin and chymotrypsin from the pancreas of the Atlantic salmon,
      Salmo salar L.
AB  - The humoral control of release of the proteases trypsin and chymotrypsin was
      investigated in the Atlantic salmon (Salmo salar L.). Intraperitoneal injection
      of a purified preparation of the peptide cholecystokinin (CCK) from pig into
      starved fish produces a dose-dependent release of both enzymes from the pyloric
      caeca/pancreas tissues which accumulate in the intestinal contents (digesta). It
      also induces release of the contents of the gallbladder. Isolated preparations of
      pyloric caeca/pancreas when incubated with CCK release trypsin and chymotrypsin.
      It is concluded that while a possible role for a neuronal component to the
      control and regulation of these enzymes cannot be ruled out, humoral control by a
      CCK-like peptide has been established. The fact that a mammalian-derived extract
      of CCK induces this response in fish indicates an early evolution and subsequent
      conservation of this control mechanism in the vertebrates.

PMID- 9185327
TI  - The effects of disulfiram and related compounds on equine hepatic alcohol
      dehydrogenase.
AB  - The reversible inhibition and the irreversible inactivation of equine hepatic
      alcohol dehydrogenase by disulfiram have been investigated. Disulfiram was found
      to be a potent competitive reversible inhibitor with KEO,I values at pH 7.0 and
      10.0 of 50 microM and 30 microM, respectively. Reversible monodentate binding to
      the active site zinc is indicated by comparison with related compounds.
      Disulfiram was also found to chemically modify and inactivate the enzyme in an
      irreversible reaction, which proceeds via the formation of a reversible enzyme
      disulfiram binary complex with a dissociation constant at pH 7.0 of 30 microM.
      The inactivation reaction has been studied over the pH 6.0 to 10.0 range. The
      dissociation constants for binding to the enzyme and the apparent first-order
      rate constants for inactivation have been determined as a function of pH. A pKa
      of 8.3 for the free enzyme has been assigned to the zinc-water ionization.
      Similar inhibition and affinity labelling kinetics are exhibited by
      diethyldithiocarbamate and by 2,2'- and 4,4'-dipyridyl disulphide, which have
      similar enzyme "on" velocity pKa values of 8.3 and 8.2, respectively. The enzyme
      is competitively protected from inactivation with disulfiram by 2,2'-dipyridyl,
      1,7'-phenanthroline, acetone, and ethanol, all of which combine with the active
      site zinc to form binary complexes. Acetate gave mixed protection against
      inactivation due to an additional interaction with the anion binding site of the
      enzyme. In view of the effect of disulfiram on ethanol metabolism and the polyol
      pathway, its importance as an aversive drug are considered.

PMID- 9185329
TI  - Comparison of the effects of a series of kappa-opioid receptor agonists upon
      sodium channel function in rat brain miniprisms.
AB  - The blockade of veratrine-stimulated phosphoinositide breakdown in rat cerebral
      cortical miniprisms has been used as a model of drug action on voltage-dependent
      sodium channels. The kappa-opioid agonists bremazocine, (+/-)- and (+)-trans-U
      50488, U-62066 (spiradoline) and U-69593 inhibited the response to veratrine with
      IC50 values of 35, 13, 15, 9, and > 100 microM, respectively. Bremazocine, at
      concentrations inhibiting the response to veratrine, did not inhibit the
      phosphoinositide breakdown response to the sodium ionophore monensin, indicating
      the specificity of the assay for sodium channels. The inhibitory actions of
      bremazocine upon veratrine-stimulated phosphoinositide breakdown were not
      antagonised by naloxone. This study thus confirms previous data suggesting that
      the kappa-opioid receptor agonists can affect Na(+)-channel function in a manner
      unrelated to their actions at kappa-opioid receptors. However, for the compounds
      tested, such effects are only found at rather high concentrations of the
      compounds.

PMID- 9185330
TI  - Effects of isoquinolinesulfonamide H-8 on Fundulus heteroclitus ovarian
      follicles: role of cyclic nucleotide-dependent protein kinases on steroidogenesis
      and oocyte maturation in vitro.
AB  - The possible role of cyclic nucleotide-dependent protein kinases in mediating the
      stimulatory actions of Fundulus heteroclitus pituitary extract (FPE) during
      ovarian steroidogenesis and oocyte maturation in vitro was investigated. Follicle
      enclosed oocytes were cultured in the presence of FPE and/or N-[2
      Methylamino)ethyl]-5-isoquinolinesulfonamide (H-8), a compound that inhibits
      protein kinase A (PKA) and cGMP-dependent protein kinase. H-8 alone (0.1-1 mM)
      promoted oocyte germinal vesicle breakdown (GVBD) in a dose-dependent manner.
      However, the process of GVBD initiated by H-8 was much slower that that triggered
      by 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17,20 betaP), the natural inducer
      of oocyte maturation in F. heteroclitus. Treatment with H-8 also increased 17,20
      betaP production by the follicles and the accumulation of this steroid in the
      media was much slower than that initiated by FPE. However, in contrast to the FPE
      action on the oocyte, which is mediated by 17,20 betaP, the stimulatory action of
      H-8 on GVBD appears to be independent of follicular steroid production, since
      aminoglutethimide (AGI), an inhibitor of steroidogenesis, did not-block H-8
      induced GVBD while inhibiting H-8 induced 17, 20 betaP production. Moreover,
      addition of H-8 to FPE-treated follicles significantly reduced 17,20 betaP
      secretion and the percentage of GVBD. These results provide further support for
      the involvement of PKA in the mechanism by which FPE stimulates ovarian
      steroidogenesis in F. heteroclitus. Furthermore, the fact that H-8 alone
      increased 17,20 betaP levels may imply that basal follicular production of this
      steroid could be induced by inactivation of cyclic nucleotide-dependent protein
      kinases. Data also indicate that inhibition of PKA and/or c-GMP-dependent protein
      kinase in the oocyte may be involved in the mechanism leading to resumption of
      meiosis in this species.

PMID- 9185331
TI  - Comparative effects of age and chronic low-level lead exposure on calcium
      mobilization from intracellular calcium stores in brain samples obtained from the
      neonatal and the adult rats.
AB  - The effects of age and chronic low-level lead exposure were studied on (a)
      [3H]IP3 and [3H]Ry binding to their respective receptors in brain membranes and
      (b) Ca2+ release from internal Ca2+ stores in brain synaptosomes obtained from
      the neonatal and adult rats. [3H]IP3 and [3H]Ry binding sites in the control
      adult membranes were greater than those in the control-neonatal membranes.
      [3H]IP3 bound to a single high-affinity site, IP3-R. Ca2+ decreased [3H]IP3
      binding to its receptor. [3H]Ry bound to at least four subspecies of Ry-Rs. KCl
      and IP3 increased, but Ca2+ caused a biphasic affect on [3H]Ry binding in brain
      membranes. IP1 and caffeine both caused greater increase in [Ca2+]I in the adult
      synaptosomes than the neonatal synaptosomes. IP4 redistributed Ca2+ from the
      caffeine-sensitive pool to the IP3-sensitive pool. IP3 increased the caffeine
      induced mobilization of Ca2+ in synaptosomes. Chronic low-level lead exposure
      decreased the binding of [3H]IP3 to its receptors in membranes, attenuated the
      IP3-induced Ca2+ mobilization in synaptosomes, abolished the IP4-induced
      redistribution of Ca2+ from Ry sensitive Ca2+ store to IP3-sensitive Ca2+ store,
      and attenuated the effects of IP1 on [Ca2+]I in caffeine stimulated synaptosomes.
      Lead exposure, however, did not affect [3H]Ry binding to Ry-R in membranes or the
      caffeine-induced increase in [Ca2+]I in synaptosomes. Chronic lead exposure
      protected IP3-R against Ca(2+)-induced inhibition in membranes. This protection
      was greater in the neonatal samples than the adult samples. This suggests that
      chronic low-level lead exposure down-regulated the IP3-induced Ca2+ mobilization
      in synaptosomes without effecting the caffeine-induced Ca2+ mobilization.

PMID- 9185332
TI  - Biochemical studies on the toxicity of 1, 1'-dimethyl-4, 4'-bipyridylium
      dichloride in the rat.
AB  - The effect of intraperitoneal administration of lethal dose (50 mg/kg) of
      paraquat on the microsomal cysteine levels in the plasma, liver and lung of adult
      male Wistar rats has been investigated using Rank Chromaspek amino acid analyzer.
      The microsomal alanine levels were also determined to help in assessing the
      extent of paraquat interference with cellular protein. DL-Buthionine-[S,R]
      Sulfoximine (BSO) and Diethyl maleate (DEM) were used to potentiate the toxic
      effect of the bipyridyl. The microsomal cysteine levels were significantly (P <
      or = 0.05) depressed in the plasma, liver and lung of the paraquat-treated rats
      compared with the saline-injected group but the alanine levels were not similarly
      affected. Probably, paraquat poisoning interferes specifically with the cellular
      cysteine content in the rat. These findings could provide a valuable information
      on the biochemical mechanism of paraquat intoxication.

PMID- 9185333
TI  - This histamine-like effects of Phallusia nigra extract: evidences for direct
      activity at H1 receptors.
AB  - The methanol extract (mol. wt lower than 3,000 Da) of the sea squirt Phallusia
      nigra has stimulatory activity on guinea-pig ileum preparations. This effect was
      inhibited by cyproheptadine and mepyramine, but not be atropine. Mepyramine
      antagonized competitively the extract activity with a pA2 of 10.09 +/- 1.12,
      suggesting a direct activity on H1 histamine receptors. The extract was also
      assayed on guinea-pig right atria, however, only a mild increase in spontaneous
      contractions was observed compared to histamine, showing that the extract was a
      rather poor activator of cardiac H2 receptors. Histamine was not detected upon
      TLC analysis of the extract by comparison with an authentic standard.

PMID- 9185334
TI  - Ergothioneine distribution in bovine and porcine ocular tissues.
AB  - Ergothioneine (ERT), is a low molecular weight, sulfur-containing antioxidant
      occurring in up to millimolar amounts in mammalian tissues. Using an improved
      HPLC assay, ERT levels have been measured and compared in bovine and porcine eyes
      and erythrocytes. The rank order of ERT levels in bovine ocular tissue was lens >
      retina = cornea > pigmented retinal epithelium (RPE) > aqueous humor (AQ) >
      vitreous humor (VIT) > sclera. In porcine ocular tissue, the rank order was
      retina > AQ > VIT > RPE > cornea > lens > sclera. ERT levels in bovine lens were
      about 250 x > that in porcine lens. Porcine erythrocyte levels were 5.5 x >
      bovine levels. Species differences were also observed in the retina, VIT and AQ
      where porcine levels were 2 to 10-fold greater than bovine levels. ERT in bovine
      lens and cornea was 35 and 14 times greater than the corresponding level of
      reduced glutathione (GSH). Porcine lens had 45 times more GSH than ERT. Values
      for ERT and GSH in other tissues from both species were of the same order of
      magnitude. These results are consistent with a role for ERT in prevention of
      oxidative damage to the eye.

PMID- 9185335
TI  - Bibliography of comparative biochemistry and physiology C generated from the
      current awareness in biological sciences database.

PMID- 9185336
TI  - Nongenetic variation, genetic-environmental interactions and altered gene
      expression. I. Temperature, photoperiod, diet, pH and sex-related effects.
AB  - The use of protein electrophoretic data for determining the relationships among
      species or populations is widespread and generally accepted. However, many
      confounding factors may alter the results of an electrophoretic study in such a
      way as to allow erroneous conclusions to be drawn in taxonomic, systematic or
      population studies. Such variables as temperature, photoperiod, salinity, pH and
      diet have been shown to influence enzymes and proteins both quantitatively and
      qualitatively. Production of distinct "cold" and "warm" isozymes or "seasonal"
      isozymes have been found in a variety of organisms. The factors that are or may
      be responsible for the appearance of these isozymes is discussed. Most studies
      that have demonstrated some apparent form of environmentally induced genetic
      expression have not determined that mechanisms responsible. However, proteolytic
      modification has been shown to produce seasonal isozymes of fructose 1,6
      bisphosphatase in rabbit liver and may account for other seasonal isozymes.
      Acclimating organisms to various conditions may actually allow detection of
      cryptic genetic variation and provide valuable data. There are many aspects to
      consider in designing acclimation experiments, and the conditions used will vary
      according to the aim of the research. Polyploidy may contribute to the genesis of
      environmentally regulated isozymes. A review of this literature follows with
      additional hypotheses and conclusions. Recommendations are given for the
      resolution of real and potential problems.

PMID- 9185337
TI  - Cardiac nuclear encoded cytochrome c oxidase subunits are decreased with copper
      restriction but not iron restriction: gene expression, protein synthesis and heat
      shock protein aspects.
AB  - Hearts from rats fed a copper-deficient (Cu-) diet have decreased levels of
      nuclear-encoded peptides of cytochrome c oxidase (CCO). Studies were conducted to
      determine whether iron deficiency would lead to a similar finding, whether mRNA
      transcripts and the chaperonin heat shock proteins (HSP) 60 and 70 from hearts of
      Cu- rats were decreased as compared with copper-adequate controls and whether
      synthesis of mitochondrial and nuclear encoded peptides differed as affected by
      diet copper. In study 1, weanling rats were assigned to one of three groups (n =
      6 in each group): (1) control copper and iron adequate fed rats; (2) Cu- rats and
      (3) iron-deficient (Fe-) rats. Western blotting of nonmyofibrillar cardiac
      proteins revealed that the nuclear encoded peptides of CCO from the Cu- rats were
      markedly decreased as compared with control and Fe- rats. Mitochondrial encoded
      subunits did not appear to differ by treatment groups. Iron-deficient rats had
      similar nuclear encoded peptide levels as those of controls. In study 2, mRNA
      transcripts from Cu- (n = 4) and control copper adequate (n = 4) rats did not
      appear to differ for subunits II and IV, which correspond to mitochondrial and
      nuclear encoded subunits, respectively. In study 3, levels of HSP 60 and 70 from
      hearts of Cu- rats (n = 3) did not differ from Cu+ rats (n = 3). In study 4,
      infusion of 3H-(4,5)-leucine into the hearts of Cu+ and Cu- rats suggested there
      was no difference in synthesis of the nuclear encoded peptides by copper status
      and some indication there was enhanced breakdown of the nuclear encoded peptides
      among the Cu- rats. As expected, more isotope was incorporated into the
      mitochondria of Cu- rats than Cu+ rats. These results demonstrate an independent
      effect of copper upon the apparent decrease in the nuclear encoded subunits of
      CCO, the effect of copper upon the CCO subunits is probably post-transcriptional
      and that translocation of the nuclear encoded subunits from the ribosomes to the
      mitochondria via the chaperonin proteins is not a primary defect in explaining
      these observations in hearts from Cu- rats and synthesis of the nuclear encoded
      subunits of CCO in not impaired in copper deficiency.

PMID- 9185338
TI  - Modulation of chloride secretion in the rat ileum by intracellular bicarbonate.
AB  - Increasing intracellular bicarbonate concentration ([HCO3-]i) inhibits calcium
      mediated Cl- secretion in rat distal colon and T84 cells. We investigated the
      effect of [HCO3-]i on Cl- secretion in rat ileum. Segments of intact ileum from
      Sprague-Dawley rats were studied in Ussing chambers and villus and crypt
      intracellular pH and [HCO3-]i were determined using BCECF. A range of crypt and
      villus [HCO3-]i from 0 to 31 mM was obtained by varying Ringer's composition.
      Basal serosal-to-mucosal Cl- flux (JsmCl) averaged 8.5 +/- 0.2 mu eq.h-1.cm-2 and
      was unaffected by changing [HCO3-]i or serosal bumetanide. Carbachol increased
      JsmCl by 3.9 +/- 0.5 mu eq.h-1.cm-2 at [HCO3-]i = 0 mM but only by 1.0 +/- 0.3 mu
      eq.h-1.cm-2 at high crypt and villus [HCO3-]i. Dibutyryl-cAMP increased JsmCl by
      2.5 +/- 0.2 mu eq.h-1.cm-2 at all [HCO3-]i. Carbachol and db-cAMP showed mutual
      antagonism at low [HCO3-]i and near-additivity at high [HCO3-]i. We conclude that
      like rat colon and T84 cells, calcium-mediated but not cAMP-mediated Cl-
      secretion in the ileum is inhibited by increasing [HCO3-]i. Mutual antagonism
      between carbachol and db-cAMP at low [HCO3-]i was present in ileum and distal
      colon but not in T84 cells.

PMID- 9185339
TI  - Energy turnover in the normoxic and anoxic turtle heart.
AB  - We examined the possibility that the heart of the tuttle Chrysemys scripta is an
      exceptional anaerobic performer, by measuring myocardial power output, lactate
      output, and estimated ATP turnover in perfused heart preparations. Over a range
      of myocardial power outputs at 5 and 15 degrees C we find that turtle hearts
      perfused with anoxic saline do not show a particularly outstanding ability to
      produce ATP anaerobically. Furthermore, at 15 degrees C anoxia reduced the ATP
      turnover rate to 50% of the normoxic rate. At 5 degrees C the anoxia-induced
      depression of ATP turnover was even more pronounced, being 4-fold lower than the
      normoxic rate. In addition, anoxia at 5 degrees C reduced the basal metabolic
      rate of the tuttle heart. We conclude that long-term cardiac tolerance of hypoxia
      in this species is more likely related to metabolic depression rather than to an
      exceptional anaerobic performance.

PMID- 9185340
TI  - Nucleoside transport in erythrocytes from bottle-nosed dolphin (Tursiops
      truncatus).
AB  - Entry of adenosine, and thymidine, into erythrocytes from adult dolphins was
      rapid, showed saturation at higher substrate concentrations, and was strongly
      inhibited by low concentrations of nitrobenzylthioinosine (NBMPR). Kinetic
      parameters were estimated from the concentration dependence of initial rates of
      tracer entry at 21 degrees C, as K(m) 0.14 +/- 0.05 mM and Vmax 24.4 +/- 1.9
      mumol/litre cell water/sec for zero trans entry of adenosine, and K(m) 0.96 +/-
      0.21 mM and Vmax 25.4 +/- 1.7 mumol/litre cell water/sec for thymidine.
      Adenosine, and thymidine, entry were inhibited by both purine and pyrimidine
      nucleosides. Mass law analysis of a saturable component of nitrobenzylthioinosine
      binding to dolphin red cell membranes gave values of Bmax 65.4 +/- 1.2 pmol/mg
      protein, and K(d) of 1.53 +/- 0.08 nM for a single class of sites. Photo
      irradiation of dolphin red cell membranes in the presence of tritiated
      nitrobenzylthioinosine led to radioactive labeling of polypeptides M(r) 52, 500
      58,000, on SDS-PAGE.

PMID- 9185341
TI  - Liver fatty acid composition and peroxisomal fatty acid oxidase activity in blue
      foxes (Alopex lagopus) and mink (Mustela vison) fed diets containing different
      levels of fish oil.
AB  - At the time of pelting (Nov.), blue foxes had a lower liver lipid content (4-5%)
      than mink (7-10%), whereas the phospholipid (PL) content was 0.5-1% in both
      species. Dietary fat content had little influence on total liver fat content but
      affected the liver fatty acid composition. Levels of n3 fatty acids were higher
      in the PL fraction than in the remaining fraction of liver lipids in both
      species. Because PL accounted for a larger part of the total liver lipids in blue
      foxes than in mink, the proportion of the total liver lipids accounted for by n3
      fatty acids was highest in blue foxes. On the other hand, the mink and foxes had
      about the same quantity of n3 per gram liver owing to higher fat content of mink
      liver. Analyses of liver lipid fatty acid composition did not reveal any
      differences between the species in their ability to metabolize n3 fatty acids
      originating from fish oil. Peroxisomal beta-oxidation activity in the liver was
      significantly higher in blue foxes than in mink. For both species the total
      activity rose as the level of dietary fish oil increased.

PMID- 9185342
TI  - L-carnitine stimulation of mitochondrial oxidative phosphorylation rate in
      isolated rat skeletal muscle mitochondria.
AB  - L-carnitine effects on mitochondrial adenosine triphosphate (ATP) production rate
      were investigated in mitochondria isolated from rat extensor digitorum longus
      (EDL) muscle. Kinetic parameters, apparent Michaelis constant for free adenosine
      diphosphate (ADP) (K(m)) and apparent maximal ATP production rate (Vmax), were
      determined in absence and presence of L-carnitine. Although the K(m) remained
      unchanged in response to L-carnitine addition when pyruvate + malate was
      oxidized, the affinity of isolated mitochondria towards ADP was decreased when
      pyruvate + palmitoylcarnitine + malate was used as substrate. As a result of L
      carnitine addition, a slight non-significant (P < 0.07) increase in Vmax was
      observed with pyruvate + malate while the increase reached the level of
      significance with pyruvate + palmitoylcarnitine + malate. Moreover, a positive
      correlation was obtained when mitochondrial ATP production rate was plotted
      against the difference between values measured with and without L-carnitine. Our
      data suggest that addition of L-carnitine to isolated rat skeletal muscle
      mitochondria can stimulate mitochondrial oxidative phosphorylation rate under
      conditions where the inhibitory effect of acetyl-CoA accumulation on pyruvate
      dehydrogenase complex activity is optimized. A change in the control of
      mitochondrial ATP flux by pyruvate dehydrogenase (PDH) complex might also occur
      with increasing mitochondrial ATP production rate, reinforcing the L-carnitine
      effects.

PMID- 9185343
TI  - Salt and water balance in the toad Bufo viridis during recovery from two
      different osmotically stressful conditions.
AB  - Toads, Bufo viridis, were subjected to two modes of osmotic stress: on soil of
      water potential approximately 5 atm and continuous partial immersion in 250
      mmol/l NaCl solution. In both conditions, plasma osmolality was greatly elevated
      involving a large increase in urea concentration and was maintained hyperosmotic
      to the external environment. After acclimation to either condition, toads were
      allowed access to tap water, and the concentrations of body fluids and gross body
      weight were followed over a 7-day period. The toads bathed only until
      preacclimation gross weight was regained, although plasma osmolality remained
      elevated. Weight remained stable thereafter. Excess plasma Na+ and Cl- were
      eliminated within a few days, whereas the urea level diminished very slowly. K+
      was closely controlled throughout, both during acclimation and recovery. The
      results suggest that B. viridis is equipped with a series of set points for
      osmotic pressure that enable it to maintain different steady states according to
      the prevailing conditions, the magnitude of the shift depending on the level of
      the imposed osmotic stress.

PMID- 9185344
TI  - A longitudinal twin study of intelligence in the second year.
AB  - Data from 408 pairs of identical and same-sex fraternal twins assessed at home
      and in the laboratory at 14, 20, and 24 months are used to describe cognitive
      development in the second year and to identify genetic and environmental
      influences on phenotypic similarity. The primary dependent variables are the
      Bayley Mental Development Index and separate constructs (based on items from the
      Bayley and the Sequenced Inventory of Communication Development) to measure
      nonverbal ability, expressive language, and receptive language. These variables
      are supplemented with laboratory tests of word comprehension, visual
      attentiveness, and memory for locations. Various patterns of development emerge
      for separate constructs, for females versus males on each construct, and for
      individuals across constructs. These data suggest developmental transitions for
      many infants during the second year, but the timing of these transitions varies
      by measure. The dependent variables tend to be intercorrelated and are reasonably
      stable for individuals, with greater stability late in the second year,
      suggesting either increasing stability or more effective measurement. Expressive
      and receptive language scores are correlated and have comparable patterns of
      change within individuals, but there are also differences (e.g., receptive
      language accounts for the most variance in MDI at each age and across ages).
      There are genetic effects on MDI at each age and effects of shared environment at
      20 and 24 months. Analyses of separate constructs reveal distinct patterns.
      Effects on nonverbal abilities are entirely genetic. Effects on language are
      primarily environmental, but genetic influence emerges for expressive language at
      20 and 24 months and for receptive language at 14 months. Visual attentiveness
      tended to reveal effects comparable to the nonverbal construct, and word
      comprehension was related to the receptive composite. Scores on the memory for
      locations task were relatively uninformative. A Cholesky decomposition is used to
      identify influences that account for the same variance at each age (i.e., promote
      continuity) and that account for new variance at each assessment (i.e., promote
      change) and to explore overlap and distinctiveness among measures at each age.

PMID- 9185345
TI  - President's address to the General Dental Council.

PMID- 9185346
TI  - Victims of the drill.
AB  - It is now widely recognised that dentistry based mainly on the restoration of
      teeth has failed to deliver dental health to our patients. There is an urgent
      need for GDPs to face up to the full implications of this failure and implement a
      truly preventive practice philosophy. We must also recognise the particular
      plight of our patients with very heavily restored dentitions who are the real
      victims of the drill and fill culture of the last 40 years. There must be no more
      additions to their ranks.

PMID- 9185347
TI  - Handle with care.

PMID- 9185348
TI  - Children's dentistry in the general dental service.

PMID- 9185349
TI  - Anaesthetic fees.

PMID- 9185350
TI  - Dental erosion in wine merchants.

PMID- 9185351
TI  - MGDS.

PMID- 9185352
TI  - E-speed film.

PMID- 9185353
TI  - Dental twinning.

PMID- 9185354
TI  - A cure for insomnia.

PMID- 9185355
TI  - The future of dental amalgam: a review of the literature. Part 4: Mercury
      exposure hazards and risk assessment.
AB  - This is the fourth article in a series of seven on the future of dental amalgam.
      It first describes toxic mercury hazards from all sources of exposure including
      dental amalgam. It begins by considering the many problems in accurately
      estimating daily mercury intakes from these sources. It then describes potential
      mercury hazards to industrial workers and the calculation of thresholds for the
      general public from industrial data. The implications of these findings to the
      production of a safe threshold for patients with dental amalgams are then
      discussed. It finally discusses the attempts which have been made to carry out a
      risk assessment of dental amalgam. In this connection it reports the reviews of
      the United States Public Health Service in 1993, the Swedish National Board of
      Health and Welfare in 1994 and the risk assessment commissioned from Canada
      Health which was reported in 1995. It also includes comments on the methods used
      in this last report.

PMID- 9185356
TI  - Technical standard of root canal treatment in an adult Scottish sub-population.
AB  - OBJECTIVE: To examine the periapical status, technical standard and frequency of
      root canal treatment in an adult population in Scotland. DESIGN: Examination of
      full-mouth periapical radiographs from 340 consecutive adult patients (8420
      teeth) attending Glasgow and Dundee Dental Hospitals for clinical examination.
      METHODS: Position and quality of the root fillings were assessed together with
      signs of periradicular radiolucencies. The influence of the type of coronal
      restoration was also assessed. MAIN OUTCOME MEASURES: Pathologies associated with
      impacted third molars and outcomes following surgical removal of third molars.
      RESULTS: 54% of the patient sample had root filled teeth. 5.6% of the teeth
      examined radiographically had root fillings, and of these, 58.1% had radiographic
      signs of periapical disease. 41% of the patients had at least one non-root canal
      treated tooth with periapical disease. 77% of teeth with post-retained crowns had
      evidence of periapical pathology. CONCLUSIONS: Root fillings judged to be
      adequate radiographically had a reduced incidence of radiolucencies. Teeth
      obturated beyond the apex had more radiolucencies than those obturated flush with
      or within 2 mm of the radiographic apex. A high proportion of post-retained
      crowns were associated with periapical pathology. There is a substantial future
      need both for root canal treatment and for standardised treatment methods.

PMID- 9185357
TI  - A problem-based preclinical course for dental students.
AB  - In September 1994 the Turner Dental School, University of Manchester, introduced
      a new curriculum in which the first 2 years were problem-oriented. The 82 dental
      students share the first year and part of the second with 252 medical students,
      making this the largest cohort of students in a problem-based learning course in
      the world. It is one of two or three dental courses of its kind. In addition to
      the problem-oriented work, the course includes a substantial informatics
      component involving computer skills. The number of lectures has been reduced to a
      maximum of four per week in the first year and seven per week in the second. Most
      of the students' learning is achieved by group work in which they study clinical
      cases and search out the basic biological background to them. At the same time
      the students consider the social and psychological implications of the cases and
      develop their own communication skills. Thus far the course has resulted in
      students having a much broader but less detailed subject knowledge. Students are
      able to integrate their knowledge more effectively. In the new kinds of
      examination developed for the course the dental students achieve marks around 5%
      lower than their medical colleagues, as in more traditional combined courses. The
      first year of the course was designed for medical students and may not therefore
      be optimal for dental students but the second year has more specifically dental
      components.

PMID- 9185358
TI  - All you wanted to know about titanium, but were afraid to ask.
AB  - Titanium is at the heart of all current dental implantology. This short question
      and answer paper reveals why.

PMID- 9185359
TI  - Taking dentistry to the top of the world on a Himalayan trek.
AB  - In October 1996 the author, a dental officer, was part of a group of ten people
      serving in the Royal Navy who walked the Annapurna circuit in conjunction with
      Five Valleys Travel and Trek Aid. The Annapurna circuit is situated in the north
      of Nepal bordering the Kingdom of Mustang and the Peoples Republic of China. It
      is a grueling 20 day trek reaching the dizzy heights of 18,000 feet, passing
      through some of the most beautiful and immense scenery in the world. The
      following is a short account of his experiences.

PMID- 9185360
TI  - Recommended normative values for thyroid volume in children aged 6-15 years.
      World Health Organization & International Council for Control of Iodine
      Deficiency Disorders.
AB  - Inspection and palpation are the traditional methods used to determine thyroid
      volume in areas of moderate-to-severe iodine deficiency. However, in areas of
      mild endemicity, and generally whenever goitres are small, ultrasonography is a
      safe, noninvasive technique that provides a more precise and objective method for
      determining thyroid volume. Ultrasonography should be undertaken by well-trained
      operators, whose correct interpretation relies on the availability of
      standardized reference criteria from populations whose iodine status is known to
      be adequate. A recent survey conducted among schoolchildren aged 6-15 years in 12
      European countries provides ultrasound data for determining thyroid volume from
      7599 subjects, and urinary iodine levels from 5709 subjects. A subgroup of 3474
      children born and living in areas where iodine intake is normal-as evidenced by
      median urinary iodine above 100 micrograms/l-furnishes data from which to derive
      thyroid volume reference values. This article presents the upper normal limit for
      thyroid volume, according to age, for the iodine-replete boys and girls in this
      subgroup, assessed using ultrasonography. In countries with a high prevalence of
      child growth retardation, thyroid volume is provisionally considered to be more
      directly a function of total body surface area. Recommended upper normal limits
      of thyroid volume, calculated according to body surface area, are also reported.
      These cut-off values are recommended for interpreting survey and surveillance
      ultrasonography data among school-age children.

PMID- 9185361
TI  - Distribution and prevalence of major risk factors of noncommunicable diseases in
      selected countries: the WHO Inter-Health Programme.
AB  - The Inter-Health Programme was launched in 1986 by WHO, with the collaboration of
      a coordination centre (National Public Health Institute, Finland) to control and
      prevent chronic noncommunicable diseases (CNCDs) among adults. Programmes for
      action were organized based on the concept that most major CNCDs share common
      risk factors and that those that are lifestyle related are modifiable through
      efficient interventions using multifactorial strategies involving community
      participation and behaviour changes carried out at the primary health care level.
      Twelve countries from all WHO Regions have joined the programme. A baseline
      survey was undertaken in all countries with a common protocol, following the
      criteria and methods employed in the MONICA Project. Altogether 36815 men and
      women aged 35-64 years were included in the present analysis from the following
      Inter-Health countries: Chile, China, Cyprus, Finland, Lithuanian SSR, Malta,
      Mauritius, Russian SFSR, United Republic of Tanzania, and USA. In addition to
      individual country analysis, centralized analysis was carried out at the Finnish
      National Public Health Institute and the Department of Community Health, Kuopio
      University, Finland. Reported here are the mean values of blood pressure, body
      mass index, and serum total cholesterol as well as specific prevalences of
      smoking, hypertension, obesity, and hypercholesterolaemia.

PMID- 9185362
TI  - Microbiological laboratory results from Haiti: June-October 1995.
AB  - From June to October 1995, the U.S. Army's 86th Combat Support Hospital was
      deployed in Haiti in support of the United Nations peacekeeping mission. The
      hospital's mission was to provide comprehensive health care to United Nations
      military and civilian personnel in Haiti. The hospital's laboratory, with
      microbiological and parasitological capability, was a critical asset in light of
      the infectious disease threats in Haiti. A total of 356 microbiological (5.4%)
      and 887 parasitological (13.4%) tests were performed, out of a total of 6628
      laboratory tests. One finding was the discovery of antibiotic-resistant urinary
      isolates of Escherichia coli. These were from community-acquired infections and
      included strains resistant to ampicillin (6/15), trimethoprim+sulfamethoxazole
      (6/15), and ciprofloxacin (2/15). Ampicillin (8/15) and
      trimethoprim+sulfamethoxazole (3/15) resistance was also noted in Shigella spp.
      However, no chloroquine-resistant strains of malaria were encountered. Dengue
      virus, also mosquito borne, was a major pathogen. Antimicrobial-resistant
      nosocomial pathogens were also encountered. Deployed laboratories should be able
      to determine antimicrobial susceptibility and perform microbial identification to
      guide clinical management, conduct medical surveillance, and detect emerging
      resistance.

PMID- 9185363
TI  - Plague foci in Viet Nam: zoological and parasitological aspects.
AB  - Reported are the results of studies over the period 1989-94 on host-flea
      complexes in small mammals and their flea ectoparasites in and around a number of
      human settlements in Viet Nam in which human cases of plague had been found.
      Collections were also made in savanna and tropical forest areas within a 10-km
      radius of the settlements. The greatest numbers of small mammals, for the most
      part Rattus spp., and of the flea ectoparasite Xenopsylla cheopis were found in
      inhabited areas. X. cheopis was not found on any feral or sylvan mammal further
      than 0.6 km from settlements. A possible link between wild and commensal mammals
      may be provided by the flea Lentistivalius klossi, a specific parasite of
      squirrels and tree-shrews but also found in very small numbers on commensal rats.
      No zoonotic foci of plague were found in the immediate vicinity of the villages
      studied and it is most likely that plague persists in a commensal rat-X. cheopis
      cycle in and around human settlements in Viet Nam.

PMID- 9185364
TI  - Seasonal variation of Opisthorchis viverrini infection in cyprinoid fish in north
      east Thailand: implications for parasite control and food safety.
AB  - Reported is the seasonal pattern of Opisthorchis viverrini metacercariae in
      cyprinoid fish in north-east Thailand. Samples of fish were collected in 1991-92
      at monthly intervals from two areas-Khon Kaen Province, where the opisthorchiasis
      transmission rate was high, and Mahasarakham Province, where the rate was low.
      Metacercarial loads in both study areas had similar seasonal patterns. High
      burdens occurred in the late rainy season and winter (July to January) with low
      burdens during the summer (March to June). The average burden for Puntius
      leiacanthus in Khon Kaen was 1.68 metacercariae per fish (127.43 per kg), higher
      than for all species of cyprinoid fish from the low transmission area. The
      intensities of infection among P. leiacanthus and Cyclocheilichthys armatus
      collected in Mahasarakham were comparable, but lower than the intensity of
      Hampala dispar (0.75 metacercariae per fish) concurrently sampled from the same
      area (P < 0.05). There was no significant difference in metacercarial load per kg
      between fish species from Mahasarakham. The results indicate that seasonal
      variation in metacercariae was a common phenomenon in areas with both high and
      low endemicity of infection. Also, the metacerarial load in fish was positively
      associated with infection levels among humans.

PMID- 9185366
TI  - Visual field constriction as a cause of blindness or visual impairment.
AB  - Reported are the results of a study of onchocerciasis in communities mesoendemic
      for savanna onchocerciasis in Kaduna State, northern Nigeria. The study involved
      6831 individuals aged > or = 5 years who underwent an extensive screening
      examination for visual function including Friedmann field analysis. A total of
      185 (2.7%) were bilaterally blind by acuity and an additional 28 (0.4%) were
      blind by visual field constriction. Also 118 (1.7%) individuals were visually
      impaired by acuity criteria. No criteria for visual impairment by field
      constriction have been established, and we therefore investigated three potential
      criteria. As a result, a further 60 (0.9%) individuals were identified with
      significant visual impairment due to field loss by the various definitions. Small
      islands of remaining peripheral field occurred in 50 individuals, while 40
      individuals had marked reduction of binocular visual field below the horizontal
      meridian. Concentric visual field constriction to < 20 degrees was found in seven
      individuals. The WHO definition of blindness currently includes visual field
      damage criteria for blindness but not for visual impairment. Visual field loss is
      recognized as a major disability. We hope that these findings stimulate
      international discussion leading to the development of satisfactory definitions
      for visual impairment by visual field constriction.

PMID- 9185365
TI  - Occupational exposure to the risk of HIV infection among health care workers in
      Mwanza Region, United Republic of Tanzania.
AB  - During 1993, we collected data on knowledge of human immunodeficiency virus (HIV)
      transmission, availability of equipment, protective practices and the occurrence
      of prick and splash incidents in nine hospitals in the Mwanza Region in the north
      west of the United Republic of Tanzania. Such incidents were common, with the
      average health worker being pricked five times and being splashed nine times per
      year. The annual occupational risk of HIV transmission was estimated at 0.27% for
      health workers. Among surgeons, the risk was 0.7% (i.e. more than twice as high)
      if no special protective measures were taken. Health workers' knowledge and
      personal protective practices must therefore be improved and the supply of
      protective equipment supported. Reduction of occupational risk of HIV infection
      among health workers should be an integral part of acquired immunodeficiency
      syndrome (AIDS) control strategies.

PMID- 9185368
TI  - Introducing quality management into primary health care services in Uganda.
AB  - In 1994, a national quality assurance programme was established in Uganda to
      strengthen district-level management of primary health care services. Within 18
      months both objective and subjective improvements in the quality of services had
      been observed. In the examples documented here, there was a major reduction in
      maternal mortality among pregnant women referred to Jinja District Hospital, a
      reduction in waiting times and increased patient satisfaction at Masaka District
      Hospital, and a marked reduction in reported cases of measles in Arua District.
      Beyond these quantitative improvements, increased morale of district health team
      members, improved satisfaction among patients, and greater involvement of local
      government in the decisions of district health committees have been observed. At
      the central level, the increased coordination of activities has led to new
      guidelines for financial management and the procurement of supplies. District
      quality management workshops followed up by regular support visits from the
      Ministry of Health headquarters have led to a greater understanding by central
      staff of the issues faced at the district level. The quality assurance programme
      has also fostered improved coordination among national disease-control
      programmes. Difficulties encountered at the central level have included delays in
      carrying out district support visits and the failure to provide appropriate
      support. At the district level, some health teams tackled problems over which
      they had little control or which were overly complex; others lacked the
      management capacity for problem solving.

PMID- 9185367
TI  - Health expectancy calculations: a novel approach to studying population health in
      Bulgaria.
AB  - The measurement of life expectancy in terms of either good or poor health is a
      novel approach to studying the health of the population in Bulgaria. The pilot
      study reported here-carried out among people aged > or = 60 years in a middle
      sized Bulgarian town-was designed to obtain information on the years of
      functional restrictions expected among the elderly. In accordance with the
      answers to a series of questions (recommended by WHO), subjects were categorized
      as disabled, handicapped, or having different states of perceived health. The
      indicators "disability-free life expectancy", "handicap-free life expectancy" and
      "healthy life expectancy" (based on self-perceived health) were calculated
      according to Sullivan's method. The results show, for example, that 8.0 of the
      16.0 years that men aged 60 years may expect to live, on average, will be free of
      disability. For men aged 80 years the figures are 1.3 of 5.5 years. For women at
      60 years and 80 years the results are 7.3 and 0.5 disability-free years of 19.2
      and 7.3 expected life years, respectively. Similar results were found for
      handicap-free life expectancies and healthy life expectancies. At all ages, the
      proportion of life in a condition free of disability, free of handicap, or in
      perceived good health is substantially lower for women than for men. Women may
      expect to live longer, but a greater proportion of their life will be spent in
      poor health. The approach presented here for measuring the health status of the
      elderly may be helpful as an aid to planning medical and social care and for the
      development of public health policies.

PMID- 9185370
TI  - Nomenclature for secreted regulatory proteins of the immune system
      (interleukins): update. IUIS/WHO Standing Committee on Interleukin Designation.

PMID- 9185372
TI  - Characteristics and sexual behaviour of individuals attending the sexually
      transmitted diseases clinic at Queen Elizabeth Central Hospital Blantyre, Malawi.
AB  - Characteristics and sexual behaviour, knowledge of HIV and knowledge of attitudes
      to and use of the condom were assessed by a questionnaire survey of a sample of
      734 patients attending a sexually transmitted diseases clinic at the Queen
      Elizabeth Central Hospital, Blantyre, Malawi. The male respondents had a mean age
      of 27.4 years compared with 24.5 for the women. Nearly two thirds of either sex
      reported more than one sexual partner during the previous year. Thirty one
      percent of the females and 43% of the males admitted having ever exchanged money
      directly for sex. Knowledge about HIV transmission and prevention, and the condom
      was generally good. Only 24% male and 45% female respondents reported having ever
      used the condom, with 27% and 43% respectively using it sometimes. No respondent
      used the condom always. The most common reported reason for not using the condom
      was partner refusal. Many of the respondents exhibited a high level of HIV risk
      behaviour.

PMID- 9185373
TI  - Hypertension in pregnancy--a major hospital cause for concern.
AB  - OBJECTIVE: To document the contribution made by hypertensive disease of pregnancy
      on maternal and foetal outcome in order to suggest possible changes in
      management. DESIGN: A descriptive study. SETTING: Harare Hospital-a tertiary
      referral hospital in Zimbabwe. SUBJECTS: Records of all women seen in the Unit
      were reviewed on a daily basis by one research fellow. MAIN OUTCOME MEASURES:
      Predefined events related to maternal and foetal outcome. RESULTS: A total of 354
      women out of 4,846 cases reviewed were admitted for hypertensive related
      problems. Seven hundred and thirteen women were admitted to the antenatal ward,
      39.8% because of hypertension; 55.6% were multiparous. Hypertensive women stayed
      in the antenatal ward for a mean of 7.9 days and gestation on admission was over
      32 weeks in 64.4% of cases. Low birthweight, preterm labour, perinatal and
      maternal mortality and all measures of short term perinatal morbidity were
      significantly increased in the hypertensive group. CONCLUSION: The results
      clearly demonstrate the reproductive health issues associated with hypertension
      in pregnancy. The discussion focuses on methods to improve the management of
      these women.

PMID- 9185371
TI  - Trends in reproductive health knowledge following a health education intervention
      among adolescents in Zimbabwe.
AB  - BACKGROUND: Unwanted teenage pregnancy, sexually transmitted infections and the
      attendant morbidity and mortality necessitate the need for understanding factors
      influencing adolescent sexuality and the implementation of programmes designed to
      improve their knowledge, reproductive behaviour, sexual and reproductive health.
      OBJECTIVE: To determine the impact of an intervention package on knowledge levels
      of various reproductive health issues through trend analysis. DESIGN: Randomized
      controlled trial of a health education intervention in schools stratified for
      representativeness. SETTING: Rural and urban secondary schools in Zimbabwe.
      SUBJECTS: 1,689 students recruited from 11 secondary schools in Mashonaland
      Central. MAIN OUTCOME MEASURE: Knowledge level before and after intervention.
      RESULTS: The demographic characteristics of the pupils at baseline, five months
      and nine months were comparable between the two groups. There was an overall
      increase in knowledge on menstruation. Students from the intervention schools
      were more likely to have correct knowledge over time on aspects of reproductive
      biology. A significant linear trend (p = 0.017) was observed in the area of
      family planning and contraception. A linear decreasing trend (p = 0.001) was
      observed on pregnancy risk. Though not significantly linear, the general trend of
      knowledge levels in all the areas of reproductive health, pregnancy risk, STDs
      and HIV/AIDS showed an upward trend, from 20% to 96%. Worth noting was that in
      all the areas the intervention group had knowledge above that in the control
      group. CONCLUSION: The reproductive health education intervention had an impact
      on aspects of reproductive biology and contraception as measured by the increased
      scoring at follow up when comparing intervention and control schools. The overall
      findings point to the need for early school based reproductive health education
      programmes incooperating correct information on reproductive biology and the
      prevention of subsequent reproductive morbidity by imparting information on non
      risk behaviour during the early developmental years.

PMID- 9185369
TI  - Prevention of diarrhoea in young children in developing countries.
AB  - An updated review of nonvaccine interventions for the prevention of childhood
      diarrhoea in developing countries is presented. The importance of various key
      preventive strategies (breast-feeding, water supply and sanitation improvements)
      is confirmed and certain aspects of others (promotion of personal and domestic
      hygiene, weaning education/food hygiene) are refined. Evidence is also presented
      to suggest that, subject to cost-effectiveness examination, two other strategies
      vitamin A supplementation and the prevention of low birth weight-should be
      promoted to the first category of interventions, as classified by Feachem, i.e.
      those which are considered to have high effectiveness and strong feasibility.

PMID- 9185375
TI  - The prevalence of nipple disease among breast feeding mothers of HIV seropositive
      infants.
AB  - OBJECTIVE: To determine the prevalence of nipple disease among breast feeding
      mothers of symptomatic HIV seropositive infants and factors associated with
      nipple disease. DESIGN: Cross sectional survey. SETTING: Harare Central Hospital
      general paediatric wards. SUBJECTS: One hundred and four symptomatic, HIV
      seropositive breast feeding infants and their mothers. MAIN OUTCOME MEASURES:
      Prevalence of nipple disease. RESULTS: The majority of the hospital admissions
      (90%) were for pneumonia. The prevalence of nipple disease was high (30.8%).
      Nipple eczema was seen in 22.1%, cracked nipples in 10.6% and sore nipples in
      10.6% of these breast feeding mothers. The odds of developing nipple disease in
      the mother if the infant had oral disease were 11.47 (95% CI 5.28 to 25.39).
      There was no significant association between nipple disease and mother's age,
      infant's age, nutrition status or mode of feeding. Malnutrition was a major
      problem. CONCLUSION: Nipple disease was highly prevalent and oral disease was the
      major risk factor for the development of nipple disease in breast feeding HIV
      seropositive mothers.

PMID- 9185374
TI  - Assessment of a take home child supplementary feeding programme in a high density
      suburb of Mutare City, Zimbabwe.
AB  - OBJECTIVE: Assessment of a child supplementary feeding programme. SETTING: Mutare
      City Health Department has a long existing, ongoing supplementary feeding
      programme for undernourished children. We assessed the programme in Sakubva,
      Mutare's oldest, largest, poorest and most densely populated high density suburb.
      During the time of assessment, after the 1994/95 poor rainy season, levels of
      undernutrition were more that double the normal levels. DESIGN: Analysis of
      clinic records. Results are illustrated with findings from students on attachment
      who studied underlying causes of undernutrition. SUBJECTS: The supplementary
      feeding programme is a health service to underweight children who attend our
      clinics. Assessment of the programme was done on all children that regularly made
      use of this service between July 1995 and May 1996 in Sakubva (n = 190). RESULTS:
      The child supplementary feeding programme does make an impact as 83% of the
      children attending regularly, improve. The impact of a child supplementary
      feeding programme in terms of growth development in undernourished children
      depends on the underlying chronic diseases that the children are presenting.
      CONCLUSIONS: Referral of children that do not improve for check up and treatment
      is urgent and should be a routine procedure in Well Baby Clinics. In an
      environment of poverty and poor weaning practices, often aggravated by underlying
      illnesses, a child supplementary feeding programme can improve growth in
      undernourished children, within the limitations of its coverage.

PMID- 9185376
TI  - A prospective study of Plantar fasciitis in Harare.
AB  - OBJECTIVES: 1. To determine the sex distribution of Plantar fasciitis in Harare.
      2. To determine the presence or absence of a calcaneal spur and its role in
      causation and hence treatment. 3. To determine unilateral or bilateral
      involvement. 4. To determine the response to steroidal injection. 5. To determine
      the role of occupation and/or activities if any. DESIGN: Patients presenting with
      heel pad pain were carefully examined, the age, sex and occupation recorded. They
      were followed up at two weekly intervals following treatment. SETTING: This
      prospective study was carried out at a private surgery in a low density suburb.
      Most patients were referred by their general practitioners and some by patients
      who had been treated successfully. A few were referred from towns in and around
      Mashonaland Central Province. SUBJECTS: All patients had to satisfy the diagnosis
      of Plantar fasciitis. Those presenting with well known causes of pain in and
      around the heel were excluded. INTERVENTIONS: All patients had radiographs of
      both heels requested. The painful heels were injected in the office with 80 mg of
      depo-medrol plus three to four mls of plain lignocaine using the lateral
      approach. RESULTS: The majority of patients (90%) were female, the mean age 48.5
      years. Most patients (60%) had no calcaneal spur, 64% had unilateral disease and
      this was predominantly left-sided. 94% had relief of their symptoms following a
      single injection. CONCLUSIONS: In this study there were more females treated for
      Plantar fasciitis, the majority responded to a single injection. The role of
      occupation and/or activities require further study.

PMID- 9185378
TI  - Scope of urinary pathogens isolated in the Public Health Bacteriology Laboratory,
      Harare: antibiotic susceptibility patterns of isolates and incidence of
      haemolytic bacteria.

PMID- 9185377
TI  - Bulbar presentation of acute post infectious polyneuropathy: a case report.

PMID- 9185379
TI  - Confounding and effect modification: their significance in medical research.

PMID- 9185380
TI  - Results from the 1995 survey of prevalent clinically diagnosed HIV infection in
      England, Wales, and Northern Ireland.
AB  - Health districts in England, Wales, and Northern Ireland were surveyed in 1996 to
      collect summary information about people with diagnosed HIV infection who
      received care under the statutory services in 1995. The survey provided
      demographic and epidemiological information about the prevalent caseload by area
      of residence, and the extent to which patients with diagnosed HIV infection
      travelled to obtain care related to it. A total of 13362 people with diagnosed
      HIV infection were reported to be resident and treated in England, Wales, or
      Northern Ireland in 1995. Forty-four per cent of these were treated outside the
      health district where they lived, with regional specialist centres attracting
      patients from wider areas. At least 13% received care from more than one
      treatment centre. This national survey of prevalent diagnosed HIV infections
      provided public health specialists with information relevant to their own
      localities without compromising confidentiality. This information complements
      surveillance data from confidential AIDS case diagnosis reports, laboratory
      reports of HIV infections, and the unlinked anonymous HIV prevalence monitoring
      programme, all of which contribute to the assessment and projection of demands on
      health and social services, and provide evidence on which to develop and direct
      national and local health campaigns.

PMID- 9185381
TI  - Gastroenteritis in children under 5 years of age in England and Wales.
AB  - Gastroenteritis is a major cause of illness in young children worldwide. The
      magnitude of this problem is underestimated, as many cases may not present for
      medical treatment and many that do present are not asked to provide a faecal
      specimen. In this study, laboratory reports of pathogens responsible for
      gastroenteritis in children under 5 years in England and Wales reported to the
      PHLS Communicable Disease Surveillance Centre from January 1990 to December 1994
      were analysed. These reports were compared with food poisoning notifications and
      mortality attributable to gastroenteritis collated by the Office of Population
      Censuses and Surveys in the same age group over the same period. Thirty-nine per
      cent of the 167630 laboratory faecal identifications were of rotavirus. Reports
      were commonest in children under 1 year of age during the winter months.
      Salmonellas and campylobacters were isolated from 16% and 15% of the specimens
      reported respectively. During the study period salmonella reporting rates rose by
      48% in this age group. Improving the microbiological quality of food and raising
      standards of food hygiene, together with increasing parental awareness of the
      possibility of food poisoning in young children, will help to reduce morbidity in
      this age group. The majority of childhood deaths attributable to gastroenteritis
      were associated with rotavirus infection. The introduction of recently developed
      vaccines against rotavirus could substantially reduce the level of morbidity in
      this age group.

PMID- 9185382
TI  - Outbreak of Salmonella enteritidis phage type 6 infection associated with food
      items provided at a buffet meal.
AB  - Preliminary enquiries following prompt notification of three cases of suspected
      food poisoning revealed that they had all attended the same three functions
      during the preceding weekend. Subsequent investigation identified 49 people with
      gastrointestinal symptoms, 13 of whom were infected with Salmonella enteritidis
      phage type 6. Forty-five of those with symptoms, including 11 with confirmed
      infection, had eaten a buffet meal at a public house. Eating egg sandwiches was
      strongly associated with infection. Defects in the kitchen structure and the
      storage and handling of the implicated food items provided the potential for
      cross contamination. Salmonella was isolated from several environmental sites,
      including a general purpose cleaning cloth. Two different quiches and pork pies,
      which were possible vehicles of infection were thought to have been contaminated
      after being brought into the kitchen. The investigation did not reveal whether or
      not shell eggs used in the sandwiches were the original source or whether they
      too had been contaminated during their preparation.

PMID- 9185383
TI  - Epidemic methicillin resistant Staphylococcus aureus.

PMID- 9185384
TI  - Apoptosis or programmed cell death.

PMID- 9185385
TI  - Symptomatology and chest roentgenographic changes of pulmonary tuberculosis among
      diabetics.
AB  - Symptoms and chest x-ray findings in 28 diabetics and 38 non diabetics with
      pulmonary tuberculosis were compared. The two groups of patients were age and sex
      matched. There was no statistical difference in respiratory or constitutional
      symptoms between the two groups. Distribution of chest x-ray involvement
      including cavitary disease was again similar in the two groups of patients. These
      findings are contrary to previous reports and beliefs that diabetics were less
      symptomatic and that x-ray findings were more frequent in lower lung fields.

PMID- 9185386
TI  - Clinico-pathological analysis of jaw tumours and tumour-like conditions at the
      Kenyatta national hospital.
AB  - This paper presents an analysis of 568 jaw tumours and tumour-like conditions
      seen at the Kenyatta National Hospital over a period of fifteen years. For
      descriptive purposes, the term tumour is used here in its wider context to cover
      both neoplastic and dysplastic jaw lesions which present primarily as jaw
      swellings. The study reveals a pattern consistent with other African series and
      suggests a more aggressive progression and younger age at onset than elsewhere.

PMID- 9185387
TI  - Malaria in Mvumi, central Tanzania and the in vivo response of Plasmodium
      falciparum to chloroquine and sulphadoxine pyrimethamine.
AB  - A study on the prevalence of malaria and the response of Plasmodium falciparum to
      chloroquine and sulphadoxine-pyrimethamine was conducted in Mvumi area of central
      Tanzania. Splenomegaly was observed at a rate of 62% and 36% in children and
      adults respectively. Crude malaria parasite rate was 55.4% in children and 32% in
      adults. Plasmodium falciparum accounted for the highest proportion (62.7%) of the
      malaria parasites in the area. This malaria parasite was sensitive to standard
      dosage of either chloroquine or sulphadoxine-pyrimethamine. Sulphadoxine
      pyrimethamine cleared the parasites to undetectable levels by day seven of
      administration whereas chloroquine cleared parasitaemia in 91% of the subjects by
      the seventh day. Despite the virtual absence of adult Anopheles mosquitoes during
      the study period, a larval survey indicated that breeding of Anopheles gambiae
      s.l. was taking place in nearby irrigation streams. Culex quinquefasciatus was
      the dominant man-biting mosquito in the area.

PMID- 9185388
TI  - Childhood epilepsy in Ilorin, Nigeria.
AB  - Ninety eight children with epilepsy attending the Neurology clinic, University of
      Ilorin Teaching Hospital over a two year period were studied prospectively. Males
      were more affected than females in a ratio of 5:3. Generalised tonic-clonic
      seizures accounted for 62.2% of the cases, and partial seizures for 17.4%.
      Infantile spasms were seen exclusively in infants less than two years old and
      absence and generalised seizures in children more than three years of age. Skull
      radiography showed abnormal findings in 11.2%. Ectroencephalography showed
      typical findings in 43.9%. Hemiplegia was the most common neurological sequelae
      (30.3%). Other sequelae include hyperactivity, irrational behaviour, expressive
      aphasia, mental subnormality, deafness, and blindness in that order. Therapy with
      a single appropriate anticonvulsant was usually effective for seizure control
      except in some patients with focal seizures, infantile spasms, severely delayed
      developmental milestones and prolonged seizures. Poor drug compliance remains the
      major constraint to adequate seizure control, further compounded in this
      environment by nonavailability of drugs and unaffordable costs.

PMID- 9185389
TI  - Zimbabwean teenagers' knowledge of AIDS and other sexually transmitted diseases.
AB  - A cross sectional anonymously administered questionnaire was used amongst 1689
      secondary school girls and boys to determine their knowledge of AIDS and other
      sexually transmitted diseases (STDs). Their knowledge was found to be very low.
      While 80% could name an STD in an open question, only 16% could recognise the
      important symptoms of the common and treatable diseases such as gonorrhoea and
      syphilis. This finding is worrying in view of the fact that these common STDs
      facilitate transmission of HIV/AIDS. The awareness of AIDs was high but when it
      came to the mode of transmission of AIDS the large majority were not aware of the
      risk of intercourse with an infected person. Furthermore, despite an intensive
      AIDS awareness campaign programme mounted by the government of Zimbabwe a large
      number of students thought that one can contract HIV/AIDS by shaking hands,
      sharing a toilet and witchcraft. Misconceptions on transmission abound. The data
      show that there is a need to review strategies of disseminating information to
      teenagers regarding STD, including AIDS, reproductive biology, sexuality and
      contraception. The best strategy may be the introduction of a reproductive health
      education curriculum in all schools starting at an early age.

PMID- 9185390
TI  - Causes of death among mental patients at Muhimbili Medical Centre, Dar es Salaam.
AB  - The clinical notes of the 146 patients who died during a five year period in the
      psychiatric ward at the Muhimbili Hospital were studied and analysed to identify
      gender, age, duration of hospital stay, psychiatric diagnosis and primary cause
      of mortality. There were 99 (67.8%) males and 47 (32.2%) females. The mean age,
      which could be established in only 105 (71.9%) instances, was 31.1 years. The
      average hospital stay was 21.6 days. The main psychiatric morbidity consisted of
      functional psychoses (52.7%), organic psychoses (37.6%), epilepsy (6.2%) and
      puerperal psychosis (2.1%). Mortality was primarily attributed to infectious
      diseases in at least half of the cases. Pyrexia of unknown origin was associated
      with death in 11.0% of cases and the cause of death could not be established in
      17.1%. Clinical notes need to be improved and greater efforts made to diagnose
      and treat concomitant physical illnesses effectively.

PMID- 9185391
TI  - Characteristics of street children in Nazareth, Ethiopia.
AB  - A census based survey was conducted in Nazareth, a town in south-eastern
      Ethiopia, to determine the number and background of the street children, in
      December 1994. 5138 street children were counted in the town during a one day
      census. 4626(90%) were males and 512(10%) were females. The age ranged from 5 to
      18 with mean age of 12.9(SD = 3.16). 312(52.3%) of the children left their
      families before their tenth birthday. 109(18.3%) were attending school at the
      time of the survey. 326(54.6%) of the children were "on" the street type with a
      house to sleep in at night and 271(45.4%) were "of" the street type and
      completely homeless. 530(88.8%) of the children had at least one of their parents
      alive. Most of the street children take odd jobs to earn a living. Only 76(12.7%)
      were found to be living on begging. From this study it was concluded that the
      number of street children was very high, and exploration of opportunities to
      rehabilitate the children who still have their families alive is recommended.

PMID- 9185392
TI  - Prevalence of antibodies to hepatitis C virus in drug-dependent patients in
      Jeddah, Saudi Arabia.
AB  - The prevalence of antibodies to hepatitis C virus (anti-HCV) in a population of
      intravenous drug users in Jeddah, Saudi Arabia was 74.6%. The anti-HCV prevalence
      in drug dependent patients who did not use the intravenous route was 10.5%. The
      anti-HCV prevalence in healthy Saudi males and in healthy non-Saudi's was 1.7%
      and 3.2% respectively. There is a need for public education to control the spread
      of the virus.

PMID- 9185393
TI  - Childhood feeding practice in north Ethiopia.
AB  - Feeding practices among 1464 under fives were surveyed in the Gondar Zuria
      district of northern Ethiopia from July 1993 to May 1994. 99.8% of the children
      in the study area were breast fed initially, 5% discontinued before six months of
      age and 15% before the end of their first year of life. The mean duration of
      breast feeding was 21.97 +/- 10.15 months. Supplementary diet was initiated
      between 4-6 months in 42.4% of the children while in 16% it was started beyond
      the first year of life. The mean age of starting supplementary feeding was 9.9 +/
      6.5 months. The most frequently used supplementary diet was the staple diet
      which has a low nutritious value. The study revealed that initiation of breast
      feeding is not a problem in Ethiopia and the major areas of concern are the early
      termination of breast feeding, the delay in initiation of supplementary diet and
      the low quality of supplementary diet. Proper and sustained education of parents
      on feeding infants and children needs continuing emphasis.

PMID- 9185394
TI  - Evaluation of growth monitoring programme in children in Kinshasa.
AB  - A high dropout rate was noted at the under five clinic of the University of
      Kinshasa Teaching Hospital. A preliminary study carried out in March 1984 on 197
      children indicated that none of them had completed the five year period of the
      growth monitoring programme. Five hundred mothers of children attending the under
      five year clinic were then randomly selected from the 1224 who registered between
      September 1983 and August 1984. They were interviewed at home during a six week
      period. This paper confirms the dropout problem. It discusses whether mothers
      should abandon the visits early. It concludes that health workers should be
      trained to advise mothers to bring their children to the programme up to five
      years though the attendance frequency may be reduced from the second year
      onwards.

PMID- 9185395
TI  - Voluntary female sterilisation via minilaparotomy: report from Burkina Faso.
AB  - We present the first study of voluntary female sterilisation in Burkina Faso. The
      average woman undergoing tubal ligation was a 37 year old, married, house wife
      para 8 with five living children. The main reasons for TL were: achieved desired
      family size (45.9%) and medical reason (29.5%). The TL was usually performed
      (77.8%) in the postpartum, using the Pomeroy technique. With a follow up of three
      to fifteen months, no pregnancy has been reported and no request for reversal
      expressed. The authors make some suggestions to increase the prevalence of TL in
      Burkina Faso.

PMID- 9185396
TI  - Randomised clinical trial to determine optimum initiation time of norgestrel
      progestin only contraception in Eldoret Teaching Hospital, Kenya.
AB  - In a randomised controlled trial to determine the optimum time of initiation of
      Ovrette, a progestin only oral contraceptive among postpartum women, who fully or
      nearly fully breast-fed their infants in the first six months, no difference was
      found between group 1 (initiating at six weeks postpartum) and group 2
      (initiating the pill at return of menses or 6 months postpartum). There were no
      pregnancies in either group during the 18 month follow-up. There were no
      significant differences in the continuation rates between the two group.

PMID- 9185398
TI  - Use of breath sounds to assist difficult intubation of the trachea.
AB  - The technique of locating the laryngeal inlet using breath sounds was attempted
      on six patients referred for appropriate management following a failed intubation
      at the Eldoret District Hospital. Five of these were successfully intubated. It
      was still impossible to intubate the sixth patient who subsequently required a
      tracheostomy.

PMID- 9185397
TI  - Dying by default, the biology of apoptosis: a review.
AB  - Apoptosis differs from necrosis in that no inflammatory changes occur. The
      understanding of apoptosis was greatly improved by the discovery of a natural
      model of apoptosis in Caenorhabditis elegans, a nematode worm. The study of this
      worm led to the discovery of two sets of genes, the prosuicide genes and the
      antisuicide genes which control apoptosis. Apoptosis is an active process that
      involves w activation of specific enzymes. The understanding of the molecular
      biology of apoptosis may in future lead to the availability of a potent weapon to
      use against cancer and to modify cell death that occurs in the neurodegenerative
      disorders.

PMID- 9185399
TI  - Delayed diagnosis and repair of total bronchial rupture: a report of two cases.
AB  - Two Ghanaian women, aged 21 and 29 years, who were involved in road traffic
      accidents sustaining blunt trauma to the chest and who had delayed diagnosis of
      their total bronchial rupture and underwent successful surgical repair 18 and 29
      months, respectively after injury are reported with a review of the literature.
      We believe these to be the first reported cases of delayed diagnosis and
      successful repair of total bronchial rupture in Tropical Africa.

PMID- 9185400
TI  - Giant juvenile papillomatosis of the breast: report of two cases.
AB  - Two cases of giant juvenile papillomatosis of the breast, a rare disease
      occurring in adolescent girls, are reported from Libya. Both cases had been
      initially misdiagnosed as phylloides tumour of the breast due to the large size
      of the tumours. Juvenille papillomatosis should be included in the differential
      diagnosis of a large breast mass, particularly in young girls.

PMID- 9185401
TI  - The present state of vitamin K deficiency bleeding in infancy.

PMID- 9185402
TI  - The need for a balanced emphasis in infertility.

PMID- 9185403
TI  - Antimicrobial resistance: implications, consequences and possible solutions.

PMID- 9185404
TI  - Epidemiological aspects of antimicrobial drug resistance.
AB  - Micro-organisms resistant to antimicrobial drugs are a problem for health workers
      worldwide. As scientists discover newer and more effective agents to manage
      emerging therapeutic challenges, the micro-organisms develop novel mechanisms of
      resistance hitherto unknown. The challenge in the present day is to understand
      the mechanisms of resistance in micro-organisms with a view to avoiding the
      emergence of resistance. For those in developing countries where health budgets
      are meagre and the cost of newer drugs ever increasing, there is need to develop
      effective policies to use the existing therapeutic choices in the most
      appropriate manner. This article highlights various epidemiological aspects of
      antimicrobial drug resistance in bacteria of medical importance that would be
      useful in the understanding of the basis for emergence and dissemination of
      resistance.

PMID- 9185405
TI  - Recent trends on bacterial resistance to antibiotics.
AB  - Antimicrobial resistance has become a major medical and public health problem.
      The main factor responsible for development and spread of bacterial resistance is
      injudicious use of antimicrobial agents which has resulted in most gram positive
      and gram negative bacteria continuously developing resistance to the
      antimicrobials in regular use at different time periods. In East Africa, among E.
      coli in urinary tract infections, more than 80% are currently resistant to
      ampicillin, cotrimoxazole and tetracycline while more than 80% of the isolates
      are still susceptible to nitrofurantoin, gentamicin and third generation
      cephalosporins. Penicillin G resistant strains of pneumococci were first reported
      in 1967 but had gradually increased to about 20% in 1991. Among group A
      streptococci, all natural strains are still sensitive to penicillin G while
      resistance to tetracycline has reached alarming proportions. In Tanzania, more
      than 65% of N. gonorrhoeae isolates are beta-lactamase producers, however,
      spectinomycin, second and third generation cephalosporins and ciprofloxacin are
      effective against most strains. Vibrio cholerae 01 strains resistant to multiple
      antibiotics are widely spread globally, however, there are recent reports
      indicating that withdrawal of the drugs can lead to loss of the antibiotic
      resistance factors. Despite varied susceptibility of N. meningitidis strains
      world wide, isolates in Tanzania are still susceptible to commonly available
      drugs including penicillin G and chloramphenicol. Available methods for control
      of spread of bacterial resistance include rational use of antimicrobial agents
      including control in animal husbandry, change to newer antimicrobials, rotational
      use of drugs and constant surveillance for emerging bacterial resistance.

PMID- 9185406
TI  - Pattern of bacterial infections and antimicrobial susceptibility at the Kenyatta
      National Hospital, Nairobi, Kenya.
AB  - To monitor clinically significant isolates and their antimicrobial
      susceptibilities, all specimens sent to microbiology laboratory of the Kenyatta
      National Hospital were cultured on appropriate media. The susceptibility of the
      isolates was performed on Muller Hinton or diagnostic sensitivity test (DST) agar
      using comparative discs diffusion technique. The results were then entered into
      Microbe Base 2 computer programme. A total of 7416 clinically significant
      isolates were collected from 1991 to 1995. The most commonly isolated organisms
      were E.coli, Klebsiella and Staphylococcus aureus. Most of these hospital
      acquired infections had multiple resistance to conventional antimicrobials,
      namely, penicillin, tetracyclines, gentamicin, trimethoprim/sulphamethoxazole and
      ampicillin. The resistance pattern was high among both gram negative and positive
      bacteria isolates. Beta-lactamase production amongst them were 51%, 69.3%, 79.6%
      respectively. Prevalence of methicillin resistant Staphylococcus aureus was
      39.8%. Addition of clavulanic acid to amoxycillin increased Staphylococcus aureus
      susceptibility three fold. The emergence of multiple drug resistance calls for a
      continuous monitoring and reviewing of antibiotic policy in the hospital and the
      country at large.

PMID- 9185407
TI  - Survey of antibiotic prescribing pattern in government health facilities of the
      Wassa west district of Ghana.
AB  - Antibiotic prescribing patterns was studied from 700 retrospective outpatient
      clinical records from seven government health facilities in the Wassa West
      district of Ghana. Prescribing patterns were compared between the district
      hospital and six health centres. The percentage of patients receiving one or more
      antibiotics was significantly more at the health centres(60.7%) than at the
      hospital(41.0%) (chi 2 = 13.6; p < 0.001). The average number of antibiotics
      prescribed per patient was 1.4 and 1.1 respectively. The commonest antibiotics
      prescribed were procaine penicillin, cotrimoxazole, benzylpenicillin,
      metronidazole and amoxycillin. Malaria, upper respiratory infections, soft tissue
      infections and diarrhoeal diseases were the commonest indications for antibiotic
      use. Factors such as the availability of diagnostic facilities, type of
      prescriber, lack of refresher training and patient demand were considered to
      significantly influence antibiotic prescribing.

PMID- 9185408
TI  - Drug resistance and plasmid profile of Shigella organisms from different
      outbreaks in Trinidad and Tobago in 1994.
AB  - The plasmid profiles of 16 Shigella species isolated from cases of bacillary
      dysentery from different areas of Trinidad and Tobago during one calendar year,
      and their resistance pattern to eight antibiotics were analysed. All isolates
      except one S. sonneistrain, were multiple resistant. Two strains (both S. sonnei)
      had nine plasmid bands which were the maximum found. There were several plasmid
      bands common among resistant strains with multiple or single resistant profiles.
      Resistance to ampicillin and sulphonamide were the most common (93.8%), followed
      by trimethroprim (25.0%), and tetracycline (6.25%). The results indicate that the
      outbreaks may not be related.

PMID- 9185409
TI  - Rational use of antibiotics in neonatal infections.
AB  - Review of the management of neonatal infections is done with the aim of guiding
      the clinician on appropriate therapy. Minimum investigations should include a
      white blood cell count including the L:T ratio and a blood culture. The bulk of
      infections at Kenyatta National Hospital newborn unit are caused by Klebsiela,
      Citrobacter and Staphylococcus aureus. During the 1990's considerable resistance
      to gentamicin has developed. Currently, cephalosporins chloramphenicol have the
      best sensitivity pattern. The diagnosis must be carefully verified at different
      stages of treatment to ensure that only those requiring antimicrobial therapy get
      it. Indiscriminate use is thus avoided. This in turn minimises development of
      antibiotic resistant organisms. Failure of response to antimicrobials sometimes
      means a non infectious cause of illness or poor supportive management. Continuous
      surveillance is recommended with emphasis on primary prevention of infection as
      well as cross infections.

PMID- 9185410
TI  - Survey of penicillin resistant pneumococci at Kenyatta National Hospital,
      Nairobi.
AB  - During a four year period, a survey of antibiotic sensitivity patterns in
      clinical isolates of pneumococci was conducted at Kenyatta National Hospital,
      Nairobi. The isolation and characterisation of Streptococcus pneumoniae was done
      using standard laboratory procedures. Sensitivity testing was by disc diffusion
      method using discs supplied by Oxoid. During the period, 45 clinical isolates
      were recorded. This figure is somewhat lower than the expected rate of
      pneumococcal isolation at the hospital. Penicillin resistance of 24% among the
      pneumococcal isolates was recorded. Among the antibiotics tested,
      amoxycillin/clavulanic acid, ceftazidime, erythromycin and chloromphenicol had
      highest activity against the pneumococci. Surprisingly low sensitivity rates were
      recorded for trimethoprim/ sulphamethoxazole and cefuroxime. Implications of
      these findings in the management of pneumococcal infections are discussed.

PMID- 9185411
TI  - HIV infection and antituberculosis drug resistance among pulmonary tuberculosis
      patients in Harar Tuberculosis Centre, Ethiopia.
AB  - A cross-sectional study was conducted to estimate HIV seroprevalence among
      infectious (smear positive) cases of pulmonary tuberculosis and to describe the
      relation between antituberculosis drug resistance and infection with human
      immunodeficiency virus. A total of 418 smear positive pulmonary tuberculosis
      patients who attended the out patient departments of Harar Tuberculosis Centre
      and two general hospitals were studied from October 1994 through January 1995.
      The majority (94%) of these patients were from the tuberculosis centre. Sputum
      cultures were positive for 338/418 (80.9%) patients. HIV seroprevalence was
      92/418 (22.0%) among smear positive and 69/338 (20.4%) among culture positive
      patients. HIV positive patients were more likely to be from urban than rural
      areas (p < 0.001). Initial resistance was not affected by HIV seropositivity.
      Secondary drug resistance was significantly higher in HIV positive patients than
      HIV negatives (p < 0.05). Although not significant, HIV positive patients were
      more defaulters than HIV negatives. Significantly higher numbers of HIV positive
      pulmonary tuberculosis patients were cases of relapse and treatment failure (p <
      0.05). Other studies are required in order to assess the impact of HIV infection
      on the spread of anti-tuberculosis resistance. Supervised and appropriate
      treatments with follow up are required in order to minimise the spread of drug
      resistant tubercle bacilli among HIV infected patients.

PMID- 9185412
TI  - Prevalence of antituberculosis drug resistance in Harar Tuberculosis Centre,
      Ethiopia.
AB  - A tuberculosis centre based, cross sectional study was carried out in order to
      describe the magnitude of anti-tuberculosis drug resistance in Harar, eastern
      Ethiopia. The study was conducted in Harar Tuberculosis Centre which is the major
      tuberculosis treatment centre in eastern Ethiopia. A total of 338 smear/culture
      positive patients were enrolled in the study between October 10, 1994 and January
      20, 1995. Exposure status was determined through interview; drug resistance was
      determined through laboratory investigation. The overall prevalence of resistance
      to one or more antituberculosis drugs was 126/338(37.3%). Initial and acquired
      resistance were 82/252(32.5%) and 44/86(51.2%) respectively. Multi-drug
      resistance (resistance to both isoniazid and rifampicin) was detected in 3.5% of
      cases who had previous history of treatment. Anti-tuberculosis drug resistance
      was significantly higher in those who had previous history treatment (p < 0.005).
      The prevalence of drug resistance is high in Harar. There is a need for periodic
      drug resistance survey. Implementation of the WHO recommended supervised
      treatment with multi-sectoral approach is suggested.

PMID- 9185413
TI  - Susceptibility pattern of uropathogenic gram negative bacilli to antimicrobial
      chemotherapeutic agents in a National Hospital in Dar es Salaam.
AB  - In a period of two months, 232 consecutive urinary tract pathogens were isolated
      from hospitalised and non-hospitalised patients. Among the isolates, 200 (86.2%)
      were gram negative bacilli, including E. coli 109 (54.5%), Klebsiella species, 44
      (22.5%), Enterobacter species 19 (9.5%), Proteus species 18 (9%), Morganella
      morganii 9 (4.5%) and Salmonella typhimurium, one (0.5%). Antimicrobial
      susceptibility testing to amoxycillin/clavulanic acid, nitrofurantoin, gentamicin
      and cefuroxime was performed using Stoke's method. Among the 109 E. coli
      isolates, 107 (98.2%), 104 (94.5%), 105(95.5% and 107 (98.2%) were sensitive to
      amoxycillin/clavulanic acid, cefuroxime, nitrofurantoin and gentamicin,
      respectively. Of the 44 Klebsiella isolates, 42 (95.5%), 41 (95.5%), 40 (90.9%)
      and 34 (77.3%) were sensitive to amoxycillin/clavulanic acid, cefuroxime,
      nitrofurantoin and gentamicin, respectively. There was no significant difference
      when the suceptibility patterns of isolates from hospitalised patients were
      compared to those from outpatients. Although the susceptibility pattern of
      urinary tract pathogens to the commonly used antimicrobial agents in the hospital
      is still favourable, there is a need to establish strategies to prevent emergence
      of resistant bacterial strains.

PMID- 9185414
TI  - Community acquired bacterial infections and their antimicrobial susceptibility in
      Nairobi, Kenya.
AB  - The purpose of the study was to determine the pattern and antimicrobial
      sensitivity on community acquired bacterial strains in Nairobi, Kenya. Clinical
      specimens collected from out-patient clinics at the Kenyatta National Hospital
      were cultured on appropriate media and identified according to Cowen and Steel's
      manual. The antimicrobial sensitivity was determined using comparative disc
      diffusion techniques. Between 1991 and 1995, there were a total of 1659 positive
      cultures comprising 30 different bacterial species. Out of the overall gram
      negative isolates (61.9%), E.coli and Klebsiella spp formed over 70%. Among the
      gram positive, Staphylococcus aureus, Enterococcus and coagulase negative
      staphylococcus spp constituting 41%, 26% and 18% respectively were the most
      common. Most organisms showed multiple resistance patterns to commonly used
      antimicrobials similar to hospital acquired infections. The gram negative
      isolates were resistant to cotrimoxazole, ampicillin, tetracyclines,
      chloramphenicol, and sulphamethoxazole. However, the sensitivity of these
      organisms to gentamicin and kanamycin was between 60 and 90%. Among the gram
      positive isolates, there was a high resistance to penicillin and tetracyclines
      (60-90%) while the resistance to lincomycin, minocycline and chloramphenicol was
      low (5-50%). All isolates were, however, highly sensitive to cephalosporins and
      fluoroquinolones. Beta-lactamase production among, E.coli, Klebsiella spp and
      Staphylococcus aureus was 48.9%, 76.7%, 76.1% respectively. Methicillin
      resistance for Staphylococcus aureus was 59.2%. Indiscriminate use of antibiotics
      in the community may have selected for resistant strains. This calls for urgent
      need to review policies on prescription practices.

PMID- 9185415
TI  - Antibiotic sale behaviour in Nairobi: a contributing factor to antimicrobial drug
      resistance.
AB  - A survey of antibiotic sale behaviour in retail chemist shops in Nairobi revealed
      that about 64% of chemists sell antibiotics without prescriptions from doctors.
      Most shops sold underdose drugs according to the request of the patient. The
      practice is more common in peri-urban than city centre chemists. Out of the 128
      chemist shops visited, 82 sold the antibiotic, 33 sent the patients to go and see
      the doctors while 13 did both. Sixty eight per cent of the chemists in the city
      centre recommended the taking of full antibiotic course to the patients while
      only 46% in peri-urban centres did so. Even after the recommendation, some of the
      chemists still sold under dose drugs. Some of the drugs were sold in envelopes
      without any instruction at all and none of the drugs sold were fully labelled.
      Only seven chemists sold septrin, the brand of co-trimoxazole requested by the
      patients, the rest sold various brands of the drug some of whom still labelled
      the brands 'septrin'.

PMID- 9185416
TI  - Experiences and studies on antimicrobial resistance in Japan: useful lessons for
      developing countries.
AB  - The use of antimicrobial drugs in Japan is remarkably high. In 1994, the total
      production cost of antimicrobial drugs amounted to 3.38 billion US dollars. The
      intensive use of broad-spectrum drugs, especially for treatment of increasing
      number of immunocompromised and elderly patients, resulted in the emergence and
      spread of antimicrobial-resistant organisms in Japan. A bacteriological study in
      a chronic care centre shows a variety of bacterial pathogens with increased
      antimicrobial resistance such as methicillin-resistant Staphylococcus aureus.
      Control measures of nosocomial infections with resistant organisms have been
      established and strengthened. This includes surveillance researches such as re
      evaluation of disinfectants.

PMID- 9185417
TI  - Antibiotic susceptibility of group A streptococci in a national consultant
      hospital in Dar es Salaam: a four year follow-up.
AB  - Seventy one Group A streptococcal strains isolated between 1992 and 1995 at
      Muhimbili Medical Centre in Dar es Salaam were found to be susceptible to
      penicillin G and cotrimoxazole. All except two strains, which showed intermediate
      susceptibility, were susceptible to erythromycin. Sixty five strains (91.5%) were
      resistant to doxycycline. The findings confirm continuing efficacy of penicillin
      G, erythromycin and contrimoxazole in treating Group A streptococci (GAS). The
      low prevalence of GAS with intermediate susceptibility to erythromycin and
      resistance to doxycycline by a majority of the GAS emphasise the need for regular
      monitoring of antibiotic susceptibility of GAS.

PMID- 9185418
TI  - Shigella serogroups identified from adult diarrhoeal out-patients in Addis Ababa,
      Ethiopia: antibiotic resistance and plasmid profile analysis.
AB  - Fifty shigella strains were isolated from 700 diarrhoeal samples collected from
      adult diarrhoeal out-patients in Addis Ababa. Among the isolates, serogroup A
      comprised 28%, B 44%, C 18% and D 10%. Among all shigella serogroups, highest
      resistance was encountered to tetracycline (74%), ampicillin (70%), cephalothin
      (64%), trimethoprim-sulfamethoxazole (52%) and chloramphenicol (50%) while least
      resistance was observed to gentamicin (0%), polymyxin B (10%) and nalidixic acid
      (14%). Gentamicin, polymyxin B and nalidixic acid were found to be the drugs of
      choice for cases of shigellosis. All drug resistant isolates analysed for
      plasmids contained multiple plasmids ranging from 1.8 to greater than 21
      Kilobases.

PMID- 9185419
TI  - Salmonella serogroups identified from adult diarrhoeal out-patients in Addis
      Ababa, Ethiopia: antibiotic resistance and plasmid profile analysis.
AB  - Forty five Salmonella strains were isolated from 700 diarrhoeal samples collected
      from adult diarrhoeal out-patients in Addis Ababa. Among the isolates, serogroup
      C comprised 31.1%, B 24.4%, S.typhi 15.6%, D 13.3%, A 8.9% and E 6.7%. Among the
      isolates, 71.1% were resistant to tetracycline, 68.9% to ampicillin, 66.7% to
      cephalothin, 57.8% to trimethoprim-sulphamethoxazole, 53.9% to kanamycin, 46.7%
      to chloramphenicol and less than 31.8% of the isolates were resistant to other
      drugs. Among S.typhi isolates, 28.6% were resistant to chloramphenicol and this
      shows the emergence of chloramphenicol resistant S.typhi strains in Ethiopia.
      Gentamicin and polymyxin B were found to be the drugs of choice for cases of
      salmonellosis including S.typhi. All drug resistant isolates analysed for
      plasmids contained multiple plasmids ranging in sizes from 1.8 to greater than 21
      Kilobases.

PMID- 9185420
TI  - Rational approach to limiting emergence of antimicrobial drug resistance.
AB  - Microbial resistance to the available antimicrobial agents continues to be a
      major problem with regard to nosocomial and community acquired pathogens. The
      development of resistance to commonly used antimicrobials is of particular
      concern when it occurs in pathogenic organisms that cause invasive disease. This
      has implications on morbidity and mortality of infectious diseases, and will also
      result in escalated costs of care due to the use of alternative antimicrobials
      which are often more costly. The increasing frequency of drug resistance has been
      attributed to combinations of microbial characteristics, selective pressure of
      antimicrobial use and societal factors that enhance the transmission of drug
      resistant organisms. The emergence of antibiotic resistant bacteria has generally
      correlated with the rise and fall of specific antibiotic use in clinical
      practice. Although the discovery of a new drug temporarily confers therapeutic
      superiority over bacterial pathogens, the subsequent rapid evolution of
      resistance limits the duration of the effectiveness of specific agents against
      pathogens. Surveillance and the development of drug policies that encourage
      judicious use of antimicrobials will help to minimise the spread of resistant
      infections. This paper reviews how this dual strategy may be used to control
      antimicrobial resistance.

PMID- 9185421
TI  - Nosocomial infection of the urinary tract: pattern of antibiotic use and drug
      resistance.
AB  - Nosocomial infection of the urinary tract is a long standing problem that pre
      dates the antibiotic era. Hospitals have remained veritable reservoirs of
      bacteria with increased numbers and types resistant to antibiotic treatment. Most
      hospitals have epidemiologists and infection control manuals but unfortunately
      most hospital staff do not follow infection control protocols. Whenever a new
      class of antibiotics become available, enthusiastic physicians rush to use them
      discarding the older and slightly less potent ones which are subsequently
      regarded as obsolete. Some individuals claim that "good medicine is supposed to
      be practiced by those physicians who give their patients the most up to date
      drugs available". However, the resistance and sensitivity pattern of bacteria
      have changed and continue to do so, varying widely even among facilities within
      the same community. Furthermore, within several years of each antibiotic
      advancement, a parallel increase in the resistant strains of previously sensitive
      bacteria has been observed. The problem of resistant pathogens has become
      particularly important within the context of nosocomial infection of the urinary
      tract. Reduced hospital stay and avoidance of bacterial resistance by rational
      and selective use of antibiotics for preoperative prophylaxis and definitive
      therapy and strict enforcement of the hospital disease control protocols must be
      encouraged.

PMID- 9185422
TI  - Antibiotic resistance pattern of Vibrio cholerae and Shigella causing diarrhoea
      outbreaks in the eastern Africa region: 1994-1996.
AB  - Between March 1994 and December 1996, 1797 rectal swabs were transported to the
      AMREF laboratory from sites in six countries in the eastern Africa region: 1749
      were cultured for Vibrio cholerae and 48 for Shigella/Salmonella. Culture,
      isolation, identification and antibiotic susceptibility testing were performed
      using standardized techniques. The isolates were categorized as sensitive or
      resistant based on standardized zones of inhibition. The rate of isolation of V.
      cholerae from rectal swabs increased progressively from less than 20% to more
      than 45% between 1994 and 1996, 80-100% of isolates of V. cholerae from Kenya and
      south Sudan, and 65-90% from Somalia were sensitive to tetracycline, although in
      1995 isolates from Mogadishu showed only 44% sensitivity. All isolates from
      Tanzania and Rwanda were 100% resistant to tetracycline. In Kenya and Somalia,
      the percentage of isolates sensitive to chloramphenicol and cotrimoxazole reduced
      markedly from 85% in 1994 to < 10% in 1996. 100% of isolates from Rwanda and
      Tanzania were resistant to chloramphenicol and cotrimoxazole while in south Sudan
      > 70% of isolates were sensitive. Nalidixic acid and erythromycin retained > 75%
      sensitivity in all areas. Shigella dysenteriae and Shigella flexneri were
      recovered from dysentery specimens in northern Kenya. Both species showed similar
      antibiotic sensitivity patterns and were sensitive only to nalidixic acid and
      furazolidone. Due to variations of resistance patterns within countries in the
      region, antibiotic sensitivity testing should be performed at the start of an
      outbreak, and antibiotic use should be restricted to severe cases of V. cholerae
      and Shigella infection.

PMID- 9185423
TI  - Review of methicillin resistant Staphylococcus aureus with special reference to
      handling of surgical patients.
AB  - If used rationally, antibiotics can cure most bacterial infections. However,
      there is an increasing tendency globally for bacteria to become resistant to
      antibiotics. In Kenya, the occurrence of methicillin resistant Staphylococcus
      aureus(MRSA) is becoming increasingly prevalent. Penicillin, despite its narrow
      antibacterial spectrum, is still widely used in developing countries in
      prophylaxis as well as in curative settings. In surgical patients, antibiotic
      resistance is seen in: patients who are immunosuppressed, patients who have
      extensive burns and compound fractures, patients requiring prolonged hospital
      stay and those with malnutrition and low serum albumen levels. Various forms of
      theatre inadequacies may also result into antibiotic resistance. There are many
      methods of controlling the spread of MRSA and they should be put into place in
      surgical units with the assistance of infection control units. This paper is a
      review of MRSA as regards its history, prevalence, modes of transmission,
      surveillance, control measures, treatment and implications for both health care
      workers and patients.

PMID- 9185424
TI  - Experience with methicillin resistant Staphylococcus aureus at the Nairobi
      Hospital.
AB  - The problem of MRSA was recognised in mid year of 1996 among both in and out
      patients at the Nairobi Hospital. The Infection Control Committee, through the
      microbiology section of the laboratory, immediately accelerated the surveillance
      programme which included culturing all the wards, beddings, sinks, utensils,
      furniture and staff. The source was identified and disinfectant methods were
      modified to eradicate the infection from the community. Relentless fight against
      the micro-organism through the recommended methods resulted in no more cases at
      the end of the year. Nosocomial infections must be recognised by all hospitals
      which must have viable infection control programmes. The Nairobi hospital has an
      active and on-going infection control programme which enabled this problem to be
      identified and solved in a timely manner.

PMID- 9185425
TI  - The use of pain reporting forms in the in-patient setting.

PMID- 9185426
TI  - Re: Practical use of rectal medications in palliative care.

PMID- 9185427
TI  - Rectal opioid medications: our experiences.

PMID- 9185428
TI  - Adverse effects of epidural spinal cord stimulation on bladder function in a
      patient with chronic spinal cord injury pain.

PMID- 9185429
TI  - Re: Metoclopramide for chronic nausea.

PMID- 9185430
TI  - Transdermal fentanyl versus sustained-release oral morphine in cancer pain:
      preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial
      Group.
AB  - Cancer patients requiring strong opioid analgesia (n = 202; mean age, 61.5 years;
      range, 18-89 years; 55% men) were recruited from 38 United Kingdom palliative
      care centers into a randomized, open, two-period, crossover study comparing
      transdermal fentanyl with sustained-release oral morphine. Patients received one
      treatment for 15 days followed immediately by the other for 15 days. Daily
      diaries were completed. Both treatments appeared equally effective in terms of
      pain control, as assessed by the Memorial Pain Assessment Card and European
      Organization for Research and Treatment of Cancer (EORTC) pain scores. Fentanyl
      was associated with significantly less constipation (p < 0.001) and less daytime
      drowsiness (p = 0.015) but greater sleep disturbance (p = 0.004) and shorter
      sleep duration (p = 0.008) than morphine. The World Health Organization (WHO)
      performance status and EORTC global quality of life scores showed no significant
      difference between treatment groups. Of those patients who were able to express a
      preference (n = 136), significantly more preferred the fentanyl patches (p =
      0.037). We conclude that, in this study, transdermal fentanyl provided pain
      relief that was acceptable to cancer patients and was associated with less
      constipation and sedation than morphine. These reduced side effects may
      contribute to patients preference for the patches.

PMID- 9185432
TI  - Comparison of patient-controlled analgesia with and without nighttime morphine
      infusion following lower extremity surgery in children.
AB  - To evaluate the usefulness of a concurrent nighttime morphine infusion in
      pediatric patient-controlled analgesia (PCA), 36 school-age children undergoing
      elective lower extremity surgery were randomly assigned to receive morphine by
      PCA alone, or PCA with a nighttime infusion of morphine (PCA+BI).
      Postoperatively, patients breathed air and had oxygen saturation recorded
      continuously for the duration of PCA use. Total morphine requirements were
      decreased in the PCA group as compared to PCA+BI patients. PCA pump activation,
      VAS pain, and sedation scores were similar between the two groups at all times.
      Compared to the PCA group, patients assigned to the PCA+BI group spent more time
      with SpO2 of 90% or less, during the nighttime infusion (P < 0.05). The use of a
      nighttime infusion of morphine did not appear to offer any advantage over the use
      of PCA alone in this patient population.

PMID- 9185431
TI  - A prospective, within-patient, crossover study of continuous intravenous and
      subcutaneous morphine for chronic cancer pain.
AB  - The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of
      morphine were compared with continuous subcutaneous infusion (CSCI) of morphine
      in patients with chronic cancer pain. Eligible patients were referred to the
      Palliative Care Program and were receiving a stable dose of CIVI of morphine. The
      design was a within-patient, one-way crossover; in which each patient provided
      data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were
      50% of the hourly dose given every 2 hours as needed. Morphine was infused
      intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric
      Infusion Pump. After baseline data, including side effects and pain assessment,
      were obtained, patients were evaluated twice daily for toxicity and analgesic
      efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed
      over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose
      was defined as no dose change, four or less rescue doses in the previous 24 hr,
      and a pain rating of none or mild. CIVI was considered equal to CSCI if these
      criteria were maintained for 96 consecutive hr. Fifty-seven patients were
      entered, and 40 were evaluable (15 women and 25 men). The median age was 67
      (range 30-83 years). All 40 participants, after maintaining a stable dose
      throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at
      least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and
      s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean
      stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue
      doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6).
      The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7).
      The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4
      (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0
      (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable
      toxicity. There were two reports of local toxicity (mild erythema) at the SC
      needle insertion point, which required a site change. All of our 40 patients had
      adequate pain control with CIVI and CSCI morphine. Of the eight participants who
      were not maintained on the same i.v. and s.c. dose, all had adequate pain control
      and a similar side-effect profile on a higher s.c. morphine dose. These data
      suggest that the i.v. and s.c. routes are equianalgesic for most patients when
      administered as a continuous infusion. Pain control and side-effect profiles are
      quite similar and acceptable. s.c. morphine is an excellent alternative to i.v.
      morphine in both inpatients and outpatients requiring parenteral morphine for
      pain.

PMID- 9185433
TI  - Children's coping with venipuncture.
AB  - Children's strategies for coping with the pain and distress of venipuncture were
      examined in this descriptive study. Eighty-five children (aged 5-13 years) were
      interviewed prior to and following blood collection. Prior to the procedure,
      children reported pain expectations and coping strategies that might be used.
      Self-reports of the pain experienced and coping strategies used were obtained
      immediately after the procedure. Twenty-seven different strategies were
      identified from the children's responses. These strategies were subsequently
      grouped into 11 coping categories: Active Involvement in Procedure, Behavior
      Regulating Cognitions, Cognitive Reappraisal, Direct Efforts to Maintain Control,
      Diversionary Thinking, Emotion-Regulating Cognitions, Information Seeking,
      Reality-Oriented Working Through, Reliance on Health-Care Interventions, Support
      Seeking, and Avoidance and Catastrophizing. Direct Efforts to Maintain Control
      was the most frequently used category. Age and gender differences were observed
      in both number and type of strategies reported by the children. Further research
      is needed to examine the observed relationship between the type of coping
      strategies generated and the children's pain experience.

PMID- 9185434
TI  - Cost-effectiveness analysis of spinal cord stimulation in treatment of failed
      back surgery syndrome.
AB  - This article presents an analysis of the medical costs of spinal cord stimulation
      (SCS) therapy in the treatment of patients with failed back surgery syndrome
      (FBSS). We compared the medical costs of SCS therapy with an alternative regimen
      of surgeries and other interventions. Externally powered (external) and fully
      internalized (internal) SCS systems were considered separately. Clinical
      management models of each of the therapy alternatives were derived from the
      clinical literature, retrospective data sets, expert opinion, and published
      diagnostic and therapy protocols. No value was placed on pain relief or
      improvements in the quality of life that successful SCS therapy can generate. We
      found that by reducing the demand for medical care by FBSS patients, SCS therapy
      can lower medical costs. On average, given current screening and efficacy rates,
      SCS therapy pays for itself within 5.5 years. For those patients for whom SCS
      therapy is clinically efficacious, the therapy pays for itself within 2.1 years.

PMID- 9185435
TI  - Spinal cord stimulation: a valuable treatment for chronic failed back surgery
      patients.
AB  - Spinal cord stimulation (SCS) has been used in the treatment of "chronic failed
      back surgery syndrome" for many years. To evaluate long-term results and cost
      effectiveness of SCS, we interviewed 69 patients treated during a period of 13
      years. Twenty-six patients stopped using SCS; there was no clear explanation for
      this unsatisfactory result in 10. Forty-three patients continued with the therapy
      and obtained good pain relief. Electrode breakage either spontaneous or due to a
      procedure to obtain better stimulation paresthesias was more frequent in the
      radiofrequency-coupled system group than in the battery group (mean +/- SEM 2.81
      +/- 2.0 versus 1.42 +/- 1.51, respectively; P = 0.0018). Ten patients obtained
      better pain relief than during the trial procedure. Some still need opioid
      analgesics, but 11 of the 16 who require these drugs obtained a synergistic
      effect when concomitantly using the stimulator. Eleven patients have returned to
      work. In our center, the application of SCS costs on average $3660 per patient
      per year. Although this seems expensive, it may be a cost-effective treatment if
      other therapies fail.

PMID- 9185436
TI  - Use of ondansetron in palliative medicine.
AB  - Ondansetron was the first of several selective 5-hydroxytryptamine (5-HT3)
      antagonists to be available as an antiemetic. Its uses in the setting of highly
      and moderately emetogenic chemotherapy and radiotherapy are well established.
      Ondansetron has also been used to manage nausea and vomiting in other patients.
      We report a retrospective analysis of its use in all 16 patients who were
      commenced on ondansetron after admission to our institution for nausea and/or
      vomiting over a 4-year period. Nine patients had advanced human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS), and seven had malignancy.
      These patients were not undergoing disease-modifying treatment and had inadequate
      responses to therapeutic doses of standard antiemetics, used either singly or in
      combination. Responses were independently reviewed and graded by two
      investigators. Response was judged at 48 hr after commencing therapy. Potential
      causes of nausea were also reviewed. Overall, 13 of 16 [81%, 95% confidence
      interval (CI) 54%-96%] derived benefit. Twelve of 15 patients (80%) with nausea
      had a demonstrable improvement, and ten of 14 patients (71%) with vomiting also
      improved. Eight of ten patients (80%) admitted with nausea and/or vomiting as one
      of their presenting problems had the symptom controlled within 48 hr of
      ondansetron therapy. Treatment with ondansetron was well tolerated, onset of
      action was rapid, and response rates were high and sustained over time. Seven of
      the 16 patients continued ondansetron therapy for more than 10 days. With minimal
      reductions in inpatient bed stays, the total costs of ondansetron could be met
      while at the same time better supporting patients remaining in the community.

PMID- 9185437
TI  - [Appropriate early open heart palliation of univentricular atrioventricular
      connection with subaortic stenosis].
AB  - Long-term conventional pulmonary artery banding deteriorates ventricular function
      in patients who have univentricular atrioventricular connection with subaortic
      obstruction. Protection of the pulmonary vascular bed and early relief of
      subaortic stenosis is essential to improve the outcome after Fontan operation.
      From January 1995 through January 1996, three infants underwent open heart
      palliation because of univentricular atrioventricular connection with subaortic
      stenosis. All infants had discordant ventriculoarterial connection. One infant
      underwent the Norwood procedure (patient 1). Two infants underwent palliative
      arterial switch operation, one with repair of aortic arch and a Blalock-Taussig
      shunt (patient 2) and the other with endoluminal pulmonary artery banding
      (patient 3). Patient 3 required a subsequent conventional pulmonary arterial
      banding. The postoperative recovery period were smooth in the all infants. All
      infants kept sufficient PO2 ranging from 34 to 37 mmHg postoperatively. On follow
      up after 16 months pulmonary artery index decreased in patient 1. On the other
      hand, angiogram demonstrated satisfactory pulmonary arterial growth in patient 2.
      There were two late death, occurring in patient 1 (sudden death) and patient 3
      (pneumonia). Patient 2 awaits a Fontan type procedure. It is difficult to adjust
      appropriate blood flow through a Blalock-Taussing shunt and a surgically isolated
      pulmonary artery is capable of inducing pulmonary distortion after Damus-Norwoood
      type operation. Whereas natural regulation of the pulmonary arterial blood flow
      by a restrictive ventricular outflow tract is come up after a palliative arterial
      switch operation. Palliative arterial switch operation is an useful alternative
      open heart palliation for neonates and early infants who had univentricular
      atrioventricular connection with subaortic stenosis.

PMID- 9185438
TI  - [Minimally invasive direct coronary artery bypass grafting (MIDCAB) without
      cardiopulmonary bypass: a case report].
AB  - A new coronary artery bypass grafting of the left anterior descending coronary
      arteries (LAD) with in situ internal thoracic artery (ITA) bypass grafts through
      a limited anterior thoracotomy was performed in a 70-year-old [correction of 60]
      patient. The left ITA-LAD anastomosis was completed without cardiopulmonary
      bypass and postoperative angiography showed a patent anastomosis. With this
      minimally invasive approach, the procedure should provide the benefits of ITA
      grafting with rapid recovery short hospital stay without complication associated
      with cardiopulmonary bypass in selected cases.

PMID- 9185439
TI  - [Factors affecting exercise capacity after coronary bypass grafting].
AB  - In order to determine the contribution of cardiac reserve and the peripheral
      muscle to exercise capacity in patients after Coronary Artery Bypass Grafting
      (CABG), 19 patients (18 males, 1 female, mean age 63.3 +/- 7.1 years, mean
      numbers of grafting 2.5 +/- 0.8) performed exercise tests at 1 week, 3 weeks, and
      3 months after CABG. Ventilatory gas was analyzed throughout the testing and
      anaerobic threshold (AT) and peak oxygen uptake (peak VO2) was determined. During
      exercise testing, the cardiac index (CI) was measured, and the change in CI
      during exercise, delta CI = (CI at peak exercise) (CI at rest), was calculated.
      O2 delivery was derived from the product of CO and the oxygen content of arterial
      blood at peak exercise. The sectional area of the thigh muscles at the level of
      10 cm above the patella was measured using a computed tomography before each
      test. Average peak VO2 at 1 week after CABG was 867 +/- 171 ml/min and it
      increased to 1,214 +/- 246 ml/min at 6 months. Average AT did not change from 1
      week to 3 weeks, however, it increased significantly from 665 +/- 122 ml/min at 3
      weeks to 873 +/- 181 ml/min at 6 months. The muscle area of the thigh increased
      significantly from 170 +/- 24 cm2 at 3 weeks after CABG to 186 +/- 27 cm2 at 3
      months. delta CI showed a tendency to increase from 6.6 +/- 1.2 l/min/m2 at 1
      week after CABG to 7.3 +/- 1.3 l/min/m2 at 3 weeks, and also showed a tendency to
      increase from 3 weeks to 6 months. Peak VO2 and AT correlated to delta CI at 1
      weeks and also it correlated significantly to both the muscle area of the thigh
      and delta CI at 3 weeks, 3 months, and 6 months after CABG. The delta value of
      peak VO2 from 1 week to 3 weeks showed a significant correlation to those of
      delta CI and O2 delivery. Moreover, the delta values of peak VO2 and AT from 3
      weeks to 3 months showed a correlation to those of delta CI and O2 delivery.
      These results suggest that both cardiac reserve and peripheral factors contribute
      to the exercise capacity up to 3 months after CABG, and, in particular, O2
      delivery are important to increase exercise capacity.

PMID- 9185440
TI  - [A clinical evaluation of the Hepcon/HMS: a new device of monitoring hemostasis
      management during cardiopulmonary bypass].
AB  - BACKGROUND: The "Hepcon/HMS", a small, protable console which can instantaneously
      measure residual whole blood heparin concentration and automatically compute the
      necessary dose of additional heparin during extracorporeal circulation and also
      compute the required dose of protamine to reverse the effect of residual heparin.
      METHOD: This study was performed in 32 consecutive patients undergoing primary
      elective cardiac operation between March and July 1996. Patients were divided
      randomly in two groups: control group and "Hepacon/HMS" group. Hematologic
      factors, total heparin dose, total protamine dose, postoperative bleeding and
      blood transfusion volume were compared between these two groups. RESULTS:
      Patients in the "Hepcon/HMS" group received significantly greater doses of
      heparin (p = 0.01) and lower doses of protamine (p = 0.01) compared with the
      control patients. CONCLUSION: By using "Hepcon/HMS", smaller amount of protamine
      to reverse residual heparin was achieved without no hemostatic derangement nor
      increase in the amount of postoperative bleeding, irrespective of the fact that
      the greater amount of heparin was administered during extracorporeal circulation
      as compared with the conventional anticoagulation protocol. It may help prevent
      the undesirable side effects of administering excessive amount of protamine,
      including depression of myocardial function, platelet dysfunction, anaphylactic
      reaction and catastrophic circulatory collapse.

PMID- 9185441
TI  - [Acute retrograde dissection of the aorta is a formidable complication in
      retrograde perfusion through the femoral artery].
AB  - To avoid this complication, we applied a Nelaton catheter (Imamura, Tokyo, Japan:
      standard type) as a guide to insert an arterial perfusion cannula (Bardic) into
      the femoral artery. Initially, the Nelaton catheter is accurately placed into the
      femoral artery through a purse string suture without applying vascular clamps on
      the artery or its branches. Then the perfusion cannula is advanced using the
      Nelaton catheter as a guide. We believe this procedure will avoid acute
      retrograde dissection of the aorta since it protects the femoral artery from
      injuries caused by the vascular clamps or the tip of the perfusion cannula.

PMID- 9185443
TI  - [Concomitant composite graft replacement of the aortic root and the aortic arch
      for type A aortic dissection].
AB  - Successful surgical treatment of type A aortic dissection with annuloaortic
      ectasia (AAE) and severely destroyed aortic root was reported. Between April 1991
      and April 1996, 26 patients with type A aortic dissection underwent the surgical
      treatment in our institute. Among those cases, 4 cases (15%) needed the total
      aortic root replacement with composite graft. Two cases had Marfan syndrome and
      AAE and aortic regurgitation. Other two cases had severely destroyed aortic root
      because of the extension and advancement of the dissection to the aortic root.
      One was the case of disrupted right coronary ostia. And another was the case of
      frank rupture and massive bleeding from the aortic root during the operation.
      Cases of AAE were treated successfully by the routine composite graft that was
      made before the operation. However, the reconstruction of the aortic root for the
      cases who had destroyed aortic root with normal relation and size of the aortic
      root was cumbersome because of non displaced coronary artery ostia and the
      relatively narrow aortic root. For these cases, composite graft was fixed just
      below the aortic valve annulus by the sutures enforced with Teflon felt strip
      from the outside of the aorta and it made the reimplantation of the coronary
      ostia easier. As for the technique of the reimplantation of the coronary ostia,
      Carrel patch technique was used because good coaptation and fixation of the
      suture line around the coronary ostia could be obtained with this technique which
      prevent the complication such as the pseudoaneurysm or the periostial aneurysm
      formation around the coronary artery in the long term period. Concomitant
      procedures were aortic arch replacement in all cases, total arch replacement with
      four vessels graft in 3 cases and hemiarch replacement in 1 case. Each operations
      were performed with the aid of selective cerebral perfusion and open distal
      anastomosis.

PMID- 9185442
TI  - [Application of alpha-hANP for the management following open-heart surgery:
      report of two cases].
AB  - Alpha-human atrial natriuretic peptide (alpha-hANP) has a vasodilating and
      diuretic action. Intravenous continuous administration of alpha hANP (0.05
      microgram/kg/min) was attempted for two patients with low urine output despite
      good hemodynamics following open-heart surgery. Following the administration of
      alpha-hANP, urine volume increased markedly, and central venous and pulmonary
      capillary wedge pressures immediately decreased. Intravenous continuous
      administration of alpha-hANP is useful for the management of patients associated
      with the volume overload following open-heart surgery.

PMID- 9185445
TI  - [A case report on mitral valve replacement associated with antiphospholipid
      syndrome in systemic lupus erythematosus].
AB  - Mitral valve replacement (MVR) was performed on a 36-year-old woman for mitral
      valve regurgitation. The patient suffered from antiphospholipid syndrome (APLS)
      with systemic lupus erythematosus (SLE). The patient required 4 times plasma
      exchanges to prevent embolization to the cerebral arteries. A decrease in the
      anticardiolipin beta 2-glycoprotein I complex level was achieved and MVR was
      performed with a relatively good postoperative course. Anticoagulation therapy
      had been continued, but one year postoperatively the patient fell down a
      staircase and suffered acute epidural hematoma. Emergency operation was
      performed. The patient, however, died due to cerebral hemorrhage.

PMID- 9185444
TI  - [Long-term late results of pericardiectomy for constrictive pericarditis].
AB  - Twenty-four cases of the constrictive pericarditis were operated on
      pericardiectomy from 1966 to 1990. One case died because of massive bleeding,
      LOS, and respiratory failure immediately after the operation. A long-term follow
      up study was performed up to 27 years (mean 13.1 years) in other cases. Ten cases
      died during the follow up period (cardiac: 6, non cardiac: 4). Five cases of the
      cardiac deaths had major complications: tabes dorsalis, chronic respiratory
      failure, pacemaker implantation, mitral regurgitation, emergency operation at
      high age (78 years old). The survival rates of 5, 10, and 15 years were 85%, 67%,
      and 58.2%, respectively (Kaplan-Meier). All of survival cases are now in NYHA I
      or II class in satisfactory. We concluded that pericardiectomy is a very
      effective treatment for constrictive pericarditis but a more careful follow up is
      required especially in cases complicated with other major problems because
      cardiac function is not so recovered as normal level after surgery due probably
      to readhesion and fibrotic changes of the myocardium.

PMID- 9185446
TI  - [A case of radical operation for right-sided infective endocarditis due to
      Pseudomonas aeruginosa concurrent with VSD in the elderly person].
AB  - The case is a 60-year-old male. He was seen at this department because of a
      slight fever of less than 37.5 degrees C from half a year earlier.
      Echocardiography revealed vegetations under the tricuspid valve and pulmonary
      valve, and on scintigraphy of the pulmonary blood flow he was diagnosed with
      multiple pulmonary infarction. Causative bacteria were not identified by blood
      culture on admission. As the intraoperative findings, vegetations were seen
      attached to the area from the septal cusp to the anterior cusp in the tricuspid
      valve. With the pulmonary valve, a part of the valvular cusp was perforated.
      After closing VSD with a patch, the vegetations attached to the valvular cusps
      were excised and the tricuspid valve was reconstructed. As for the pulmonary
      valve, valve replacement was performed because of the destructive degeneration of
      the valvular cusp. Pseudomonas aeruginosa was detected on culture of the tissue
      of the valvular cusp resected during operation. Post operative course was
      uneventful. The patient was discharged on the 21st postoperative day.

PMID- 9185447
TI  - [A surgical case of severe Ebstein's anomaly, pulmonary atresia in the neonate:
      experience of modified Starnes operation].
AB  - We report a surgical case of severe Ebstein's anomaly associated with pulmonary
      atresia in the neonate. The baby had remarkable cardiomegaly (CTR > or = 90%)
      soon after birth and presented severe respiratory distress. He underwent modified
      Starnes operation (closure of tricuspid valve using a perforated patch,
      enlargement of interatrial communication, modified Blalock shunt, and PDA
      ligation) at the age of 12 days. He survived the procedure and cardiopulmonary
      failure was improved. However, he died from arrhythmia on the 3rd postoperative
      day. We think this procedure is useful regard to improvement of cardiopulmonary
      failure due to this fatal congenital heart disease.

PMID- 9185448
TI  - [Combined superior-transseptal approach to left atrial myxoma].
AB  - A 60-year-old woman was referred to our hospital for treatment of an intracardiac
      tumor Echocardiography revealed a 47 x 30 mm tumor in the left atrium which had a
      short stalk attached to the atrial septum. At operation, a large left atrial
      myxoma was extirpated using a combine superior transseptal approach. Through this
      incision, exposure of the left atrial myxoma and it stalk was excellent and
      removal of the myxoma was easily performed with minimal minpulation.
      Postoperative arrhythmias related to the operative procedures were not observed.
      The patient recovered uneventfully. The operative technique and indications of
      the combined superior transseptal approach to the left atrium are discussed in
      this paper.

PMID- 9185449
TI  - [Excision of a chronic expanding hematoma developing after thoracoplasty: a case
      report].
AB  - The patient was a 56-year-old woman who had undergone thoracoplasty for right
      pulmonary tuberculosis 31 years previously. She consulted her local physician
      complaining of right shoulder pain. Chest X-rays revealed a mass of the thoracic
      wall, and the patient was referred to our department. Because of the difficulty
      in making a diagnosis by needle biopsy and of increased pain, operation was done.
      The mass was covered by a fibrous capsule, and its center was composed of
      structure-less material including fibrin and blood cells. A diagnosis of chronic
      expanding hematoma developing after thoracoplasty was made. Beneath the hematoma,
      a 5 mm diameter hole communicated with the thoracic cavity. Chronic inflammation
      at this site appeared to have caused the hematoma.

PMID- 9185450
TI  - [A case of non-smoking female with peripheral small lung squamous cell carcinoma
      discovered after operation of spontaneous pneumothorax].
AB  - We have experienced a lung cancer patient discovered after operation of
      pneumothorax by chance. The patient was 44-year-old female who had been followed
      up for right pneumothorax in menstruation. She got pneumothorax in menstruation
      recurrently complained of chest pain. Chest X-p revealed right pneumothorax. We
      never discovered views of catamenial pneumothorax by thoracoscopy. Partial
      resection of hypertrophic pleura of right S1 was performed by video assist
      thoracoscopic surgery. Histological diagnosis was bulla formation with a tiny
      focus of squamous cell carcinoma in situ. In addition, right upper lobectomy and
      lymph node dissection were performed. Metastasis was not recognized any lymph
      node. No recurrence has been observed for 17 months.

PMID- 9185451
TI  - [A case of mediastinal tuberculous lymphadenitis with tracheal stenosis].
AB  - 68-year-old female was introduced our hospital for productive cough and dyspnea.
      Chest X ray film showed right upper mediastinal mass and tracheal stenosis. Chest
      CT showed mediastinal mass with calcifying lesion. ESR at 1 hour was 50 mm and
      CRP was 1.08 micrograms/ml. Because of progressive dyspnea, the operation was
      performed without further assessment. We found a mass of adhesive lymph nodes by
      the side of trachea. We removed it and it turned out to be tuberculous
      lymphadenitis. Postoperative PPD skin test showed strongly positive reaction. She
      has taken medication by antituberculous drugs and lives well without
      complications.

PMID- 9185452
TI  - [A case of bronchial stenosis due to postoperative inflammation treated with
      expandable metallic stent].
AB  - We presented a 61-year-old man who had undergone a left sleeve upper resection
      because of a squamous cell carcinoma of the upper lobe of the left lung. At 5
      weeks after the operation, the anastomosis between the left main bronchus and the
      left lower bronchus became stenotic, therefore pneumonitis occurred below the
      anastomosis. Because of the inflammatory granulo stenosis for short time, we used
      an expandable metallic stent to save a residual lung function of the operated
      side. The anastomosis between the left main bronchus and the left lower bronchus
      was kept open satisfactorily, and in the late postoperative periods the residual
      lung function recovered until the levels of predicted residual lung function.

PMID- 9185453
TI  - [A case of bilateral pneumothorax successfully treated with surgery associated
      with amyotrophic lateral sclerosis having been controlled with artificial
      ventilation].
AB  - We reported a case of bilateral pneumothorax, which was successfully treated with
      surgery, associated with amyotrophic lateral sclerosis (ALS). The patient had
      been controlled with artificial ventilation at the time of surgery. Prognosis of
      ALS is absolutely poor, and the life expectancies for patients with ALS are
      presumed several years, even though they are controlled with artificial
      ventilation. We applied a surgical treatment for a patient with ALS who developed
      bilateral pneumothorax as a life saving procedure.

PMID- 9185454
TI  - [Thymic carcinoid: a case report of complete surgical resection using internal
      mammary artery (IMA) retractor].
AB  - Carcinoid tumor of the thymus is a rare tumor and discovered not infrequently at
      advanced stage. A 56-year-old male was admitted to our hospital with severe chest
      pain. Chest X-ray film and CT scan, revealed a tumor mass in the anterior
      mediastinum. The patient underwent extended thymectomy including tumor completely
      through median sternotomy in combination with partial resection of pericardium,
      mediastinal pleura and left upper lobectomy using internal mammary artery (IMA)
      retractor. The microscopic findings of the tumor revealed carcinoid Invasion to
      pericardium and lung was found microscopically. After the operation he has been
      treated by radiotherapy and any regrowth of the tumor has never been detected for
      32 months. This case who had been undergone complete resection using IMA
      retractor followed by radiotherapy seemed to have better prognosis. Accordingly,
      extended thymectomy including tumor should be carried out for thymic carcinoid,
      and the IMA retractor is useful for complete surgical resection through median
      sternotomy.

PMID- 9185455
TI  - [A review of pregnancy-induced analgesia].
AB  - Pregnancy-induced analgesia is of interest to anesthesiologists because of a
      general clinical impression that a parturient has a lowered requirement for
      anesthetics and analgesics. This fact may be mainly explained that endogenous
      analgesic mechanisms are stimulated by pregnancy. It has been suggested that
      stress activates natural pain-inhibitory systems mediated by endogenous opioid
      and non-opioid mechanism. Activation of intrinsic analgesia systems by stress is
      described based on a review of literature. This paper will give an overview of
      experimental and clinical studies regarding pregnancy-induced analgesia and will
      discuss mechanisms and potential implications for novel therapeutic approaches.

PMID- 9185456
TI  - [Effect of nitrous oxide at sub-MAC concentrations on sevoflurane MAC in adults].
AB  - The interaction of sevoflurane and nitrous oxide (N2O) on the MAC was studied in
      the four groups of patients between 30-60 years of age scheduled for
      laparotomies. Patients received one of four different concentrations of N2O [0%
      (n = 14), 25% (n = 16), 50% (n = 15), or 70% (n = 18)]. Anesthesia was induced
      with sevoflurane and N2O using a semiclosed circuit with a carbon dioxide
      absorber. After endotracheal intubation, sevoflurane and N2O end-tidal
      concentrations were adjusted to predetermined concentrations until the skin
      incision was made. The MAC values for sevoflurane in O2 and the presence of 25%,
      50%, and 70% N2O were 1.68%, 1.33%, 0.82% and 0.55%, respectively. A regression
      analysis through all four data points yielded a linear relationship (r = -0.997).
      The requirement of sevoflurane decreased by approximately 1% for each 1% of N2O
      administered at three N2O concentrations. The extrapolated MAC value for N2O was
      102%. The MAC values of sevoflurane in O2 and N2O were similar to the previously
      reported values. We conclude that in adults, N2O concentrations in the dose range
      0-70% reduce sevoflurane MAC in a linearly additive manner.

PMID- 9185457
TI  - [Effects of steroids on hepatic ATP and L/P ratio in rats subjected to acute
      hemorrhage].
AB  - Both steroids and hemorrhage may affect the hepatic energy metabolism. The
      effects of steroids (5 mg.kg-1 of methylpredonisolone, 50 mg.kg-1 of
      methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of
      hydrocortisone) on hepatic ATP level and L/P ratio were evaluated in rats under
      acute hemorrhage. There were no significant differences in the hepatic ATP levels
      and L/P ratio among 5 groups. However, the base excess in 3 steroid groups (50
      mg.kg-1 of methylpredonisolone, 25 mg.kg-1 of hydrocortisone and 250 mg.kg-1 of
      hydrocortisone) was significantly higher than that in the control group. This
      result suggests that steroids may improve the metabolic acidosis during acute
      hemorrhage.

PMID- 9185458
TI  - [The effect of low-dose prostaglandin E1 on intra- and post-operative liver
      function].
AB  - We investigated the effects of low-dose prostaglandin E1 (PGE1) on intra- and
      post-operative liver function in 109 adult patients undergoing upper abdominal
      surgery. Patients were divided into 2 groups; Control group (n = 42) and PGE1
      group (n = 67). In PGE1 group, PGE1 was infused throughout surgery at a rate of
      0.02 microgram kg-1 min-1. In both groups, anesthesia was maintained with a
      combination of inhalational and thoracic epidural anesthesia. Epidural anesthesia
      was maintained with 1.5% lidocaine infused epidurally at a constant rate (8 +/- 2
      ml.hr-1). The continuous epidural infusion of lidocaine was initiated before
      surgery and discontinued at the end of surgery. Preoperative and postoperative
      liver function was evaluated with blood chemistry examination. Intraoperative
      liver function was evaluated in 84 patients (33 in control group and 51 in PGE1
      group) by measuring plasma lidocaine concentration. Plasma lidocaine
      concentration was determined 1 and 3 hours after the initiation of lidocaine
      infusion and 0 and 2 hours after its termination. There were no differences
      between the groups in doses and infusion rates of lidocaine. In both groups,
      lidocaine concentration increased progressively as infusion was continued.
      Lidocaine concentration was significantly lower in PGE1 group than in control
      group at the end of the infusion. In 22 patients in control group and 35 in PGE1
      group who received high-dose lidocaine (> 8 mg.kg-1), lidocaine concentration
      remained significantly lower in PGE1 group than in control group throughout the
      infusion period. The difference in lidocaine concentrations between the groups
      increased progressively as infusion was continued, though the doses and the
      infusion rates of lidocaine were not different between the groups. Postoperative
      liver function did not differ between the groups. Because removal of lidocaine
      from blood to liver parallels hepatic blood flow, the lower plasma lidocaine
      concentration in PGE1 group indicated that hepatic blood flow was higher and
      liver function was better-maintained with PGE1 during anesthesia and surgery. Low
      dose PGE1 thus improved intraoperative liver function during upper abdominal
      surgery.

PMID- 9185459
TI  - [Postoperative epidural fentanyl administration in patients for hysterectomy with
      para-aortic lymph node resection].
AB  - In our experience, continuous epidural administration of fentanyl in doses of
      12.5 micrograms.h-1, has not been sufficient to relieve postoperative pain in
      patients after hysterectomy with para-aortic lymph node resection. Thus, a
      prospective, randomized, single-blind study was performed to compare the
      analgesic efficacy of fentanyl 25 micrograms.h-1 with 12.5 micrograms.h-1 in
      these patients for 48 hours after surgery. Twenty-one women undergoing
      hysterectomy with para-aortic lymph node resection were allocated into three
      groups; Group C (control, n = 7): fentanyl 12.5 micrograms.h-1, infusion rate 2
      ml.h-1, Group S2 (double speed, n = 7): fentanyl 25 micrograms.h-1, infusion rate
      4 ml.h-1, and Group C2 (double concentration, n = 7): fentanyl 25 micrograms.h-1,
      infusion rate 2 ml.h-1. At postoperative 0, 2, 6, 12, 24, and 48 hours, the
      degree of analgesia was evaluated by visual analogue scale (VAS) and verbal pain
      scores at both rest and movement. Groups S2 and C2 showed significantly lower VAS
      scores than group C at the postoperative 6- and 24-hour points. At movement, the
      analgesic efficacy was not sufficient in any groups, but, at rest, groups S2 and
      C2 experienced significantly less pain than the group C. The degree of pain
      relief was not different between groups S2 and C2. In conclusion, epidural
      fentanyl 25 micrograms.h-1 provided significantly superior analgesia compared
      with epidural fentanyl 12.5 micrograms.h-1.

PMID- 9185460
TI  - [Effects of amrinone on oxygen demand-supply relationship after cardiopulmonary
      bypass in patient undergoing coronary bypass surgery].
AB  - We evaluated the effects of amrinone on oxygen demand-supply relationship after
      cardiopulmonary bypass (CPB) in patient undergoing coronary bypass surgery
      comparing with the patients not receiving amrinone. In amrinone treated patients
      bolus dose of amrinone 1.5 mg.kg-1 was administrated into the reservoir of CPB
      and followed by continuous infusion at a rate of 5 micrograms.kg-1.min-1.
      Hemodynamics and blood gas (arterial and mixed venous) measurements were carried
      out immediately after CPB, 1 hour after CPB and after the chest closure. After
      the chest closure, cardiac index and oxygen supply in amrinone treated group were
      significantly higher and systemic vascular resistance was significantly lower
      than in non-treated group. Left ventricular stroke work index, rate pressure
      product and oxygen consumption showed no significant difference between the two
      groups. These data indicate that the amrinone treated patients preserved better
      oxygen demand-supply relationship after CPB compared with the non-treated
      patients undergoing coronary bypass surgery.

PMID- 9185461
TI  - [Changes in alpha 2-adrenoceptor binding nature in guinea-pig brain following the
      development of morphine dependence].
AB  - We examined the effect of morphine dependence on alpha 2-adrenoceptors in guinea
      pig brain. We also studied the influence of clonidine on the naloxone-induced
      withdrawal signs. 1. Guinea-pigs were implanted subcutaneously with MS contin
      (300 mg.kg-1). Two days after implantation, the binding of 3H-UK14304 (alpha 2
      selective ligand) to brain membranes prepared from morphine dependent and control
      animals was determined. Scatchard plot of the saturation binding data revealed an
      increase in Bmax values and no change in the Kd values from dependent animals.
      These results indicate that brain alpha 2-adrenoceptors are up-regulated in
      morphine dependent guinea pigs. 2. Subcutaneous injection of naloxone on the 2 nd
      day after implantation caused characteristic withdrawal symptoms. Clonidine has
      been shown to reduce some opiate withdrawal signs in morphine-dependent animals.

PMID- 9185462
TI  - [Changes in opioid receptor binding nature in rat brain and spinal cord following
      formalin or carrageenan-induced nociception].
AB  - Previous reports demonstrated the regulation of opioid and their receptor in
      nociception, but it is not clear how nociceptive activation may alter opioid
      receptor binding nature. We determined the change of mu, delta and kappa opioid
      receptor types in brain and spinal cord homogenates obtained from animal models
      receiving nociceptive treatment. 1) Rats received a subcutaneous injection of
      formalin and carrageenan into planter aspect of a hindpaw. These agent-injected
      animals were observed for appearance of pain-related behavior (guarding of the
      treated paw) within 2-3 hour after treatment. Following these pain behavior, rats
      were decapitated and brain and spinal cord were removed rapidly. 2) The binding
      of 3H-DAGO (mu agonist), 3H-DPDPE (delta agonist) and 3H-EKC (kappa agonist) to
      brain and spinal cord membranes prepared from nociceptive treatment and control
      rats was determined. Using these tracer 3H-opioid ligands, we failed to see any
      change in the total number of opioid binding sites (Bmax values) or the affinity
      constant (Kd values) for binding in whole brain and spinal cord. These results
      indicate that in these animal models which use experimentally induced
      inflammation to stimulate a condition of nociception, there appears to be no
      alteration in the levels of mu, delta or kappa binding sites.

PMID- 9185463
TI  - [Adrenergic receptors and alpha 2 agonists--1) Molecular biological study of
      adrenoceptors].
AB  - Molecular biological studies have established classification of adrenergic
      receptors 40 years after Prof Ahlquist first classified them into alpha and beta.
      They are now classified into 9 subtypes consisting of 400 to 480 amino acids.
      They belong to a super-family of G-protein coupled receptors. Based on the amino
      acid sequence, the topography of adrenoceptors is depicted as a snake model
      twisting itself back and forth through the membrane 7 times.

PMID- 9185464
TI  - [Preventive use of diltiazem to suppress supraventricular tachyarrhythmia in the
      patients after esophagectomy].
AB  - We investigated the efficacy of preventive use of diltiazem to suppress
      supraventricular tachyarrhythmia such as paroxysmal atrial tachycardia (PAT) and
      atrial fibrillation (Af) in the patients who underwent transthoracic
      esophagectomy. We divided 52 patients into 2 groups; the diltiazem group (n = 26)
      and the control group (n = 26). In the diltiazem group continuous intravenous
      infusion of diltiazem (1-3mcg.kg-1.min-1) was started when the patient's heart
      rate remained over 110.min-1 without any predisposing factor. On the other hand,
      in the control group we did not use it preventively. In both groups, we did not
      restrict the use of antiarrhythmic agents if necessary. We recognized PAT or Af
      in the control group (54%) more often than in the diltiazem group (19%). PAT or
      Af seldom occurred after the 4th post-operative day in the both groups. Serum
      diltiazem concentrations of 9 patients after about 10 hours infusion showed great
      variation (between 30 and 250 ng.ml-1). In 7 of them the diltiazem concentration
      increased as the duration of infusion was prolonged. However, we did not observe
      bradyarrhythmia. We consider that the continuous diltiazem infusion is effective
      in suppressing supraventricular tachyarrhythmia after esophagectomy.

PMID- 9185465
TI  - [Lack of hyperglycemic rebound after insulinoma removal: two case reports].
AB  - Two cases of anesthetic management for insulinoma were reported. The first
      patient, a 54-year-old man, suffering from repeated episodes of fasting
      hypoglycemia was scheduled for removal of insulinoma developed in the pancreas
      under isoflurane-nitrous oxide anesthesia. Preanesthetic plasma glucose
      concentration was 57 mg.dl-1. Glucose was continuously administered intravenously
      to maintain plasma glucose around 150 mg.dl-1. The second patient, a 65-year-old
      man suffering from several episodes of fasting hypoglycemia was scheduled for
      removal of insulinoma in the pancreas under isoflurane-nitrous oxide anesthesia.
      Preanesthetic plasma glucose was 103 mg.dl-1. An artificial pancreas was used to
      maintain plasma glucose at 140 mg.dl-1. In these patients, hyperglycemic rebound
      was not observed after removal of the insulinoma, and their perioperative courses
      were uneventful. Although relatively low immunoreactive insulin levels might
      relate, fine management of fluid and metabolism during preoperative period was
      thought as one of the reasons that hyperglycemic rebound did not occur in these
      patients. For the safe management of the patients with insulinoma, we recommend
      to maintain plasma glucose at the levels of mild hyperglycemia to prevent
      hypoglycemic episodes until the end of the removal.

PMID- 9185466
TI  - [The effect of vasodilator on the occurrence of postoperative shivering and the
      fall of core temperature].
AB  - We evaluated the effect of intraoperative vasodilator therapy on the occurrence
      of postoperative shivering and the fall of core temperature during 37 abdominal
      operations by the stepwise multiple regression analysis. As the vasodilator, we
      used PGE1 at the dose of 0.02-0.05 microgram.kg-1.min-1. In the vasodilator
      group, postoperative peripheral surface temperature was high and the occurrence
      of shivering was low. And intraoperative and postoperative core temperatures were
      not affected by that therapy. From these results, we conclude that intraoperative
      vasodilator therapy suppressed the occurrence of postoperative shivering without
      a fall of core temperature.

PMID- 9185467
TI  - [The change of oxygen consumption and oxygen delivery in patients undergoing
      heart surgery during perioperative period].
AB  - We examined the changes of oxygen consumption (Vo2), oxygen delivery (Do2) and
      Vo2/Do2 in 38 patients undergoing cardiac surgery with cardiopulmonary bypass
      (CPB) during perioperative period. There were no significant correlations between
      Svo2 and cardiac index. The Vo2/Do2 showed a good level at pre-CPB and 1 hour
      after CPB, but the value became deteriorated 4 and 12 hours after CPB. These data
      suggest that we should be careful about the oxygen debt in tissue 4 and 12 hours
      after CPB.

PMID- 9185468
TI  - [Preoperative flurbiprofen provides pain relief after laparoscopic
      cholecystectomy].
AB  - In a single-blind randomized prospective study, postoperative pain was assessed
      in 60 patients undergoing elective laparoscopic cholecystectomy with three types
      of anesthesia: standardized general anesthesia (control group), preoperative 50
      mg flurbiprofen as an addition to the same method of general anesthesia
      (flurbiprofen group), and conventional combined epidural and general anesthesia
      with epidural administration of 0.25% bupivacaine 5-8 ml and 0.1-0.2 mg
      buprenorphine after surgery (epidural group). After the operation we found that
      the average time from the end of surgery to the first request for an analgesic
      was 3.9 h, 22.7 h and 43.7 h in the control, flurbiprofen and epidural group,
      respectively. Substantially it was longer in the flurbiprofen and epidural group
      than in the control group (P < 0.01 and < 0.001, respectively). Patients in the
      control group requested analgesics for a longer period of time after the initial
      request compared with patients in the other groups. Our results indicate that
      postoperative pain can be reduced when flurbiprofen is added to general
      anesthesia before surgery, although use of flurbiprofen was not as effective as
      the conventional combined epidural and general anesthesia used for treating pain
      after laparoscopic cholecystectomy.

PMID- 9185469
TI  - [Anesthetic management using transesophageal echocardiography during removal of a
      cardiac myxoma].
AB  - Removal of a cardiac myxoma can be complicated by mitral stenosis, arterial
      embolism and so on, all of which may be life-threatening but difficult to
      diagnose. We describe the use of transesophageal echocardiography (TEE) for the
      anesthetic management of two patients undergoing removal of a large myxoma in the
      left atrium (LA). The first case is a 78-yr-old woman, who was suffering from
      cardiac cachexy with a large LA myxoma. The anesthetic management of her surgery
      required the prevention of a decrease in cardiac output caused by anesthetic
      agents, massive bleeding and surgical procedures. The second case is an
      asymptomatic 60-yr-old man with LA myxoma, which appeared adherent to the mitral
      orifice in diastole. The goal of the anesthetic management of him was to prevent
      the obstruction of transmitral blood flow caused by the decrease in preload on
      the heart. Throughout the surgeries, TEE monitoring was conducted and helped
      decide the doses and/or rate of inotropes and vasodilators as well as the
      transfusion of fluid and blood to obtain stable circulatory conditions. It was
      also found to be of considerable value in understanding the pathophysiology of
      the tumors in LA. In conclusion, TEE monitoring during the surgery can be of much
      use both in the diagnosis and the anesthetic management of a patient with a large
      LA myxoma.

PMID- 9185470
TI  - [Perioperative risk factors and anesthetic management of patients for carotid
      endarterectomy].
AB  - Data from the records of 142 patients for carotid endarterectomy at Chugoku Rosai
      General Hospital between 1983 and 1995, were evaluated concerning perioperative
      risk factors and anesthetic management. As a preoperative anesthetic risk, the
      incidence of hypertension was the commonest (76%), and there was a significant
      incidence of ischemic heart disease (18%). Fentanyl and isoflurane have been used
      for anesthesia recently and the patients were closely observed and cared in the
      intensive care unit postoperatively. In order to prevent cerebral ischemia during
      the occlusion of the internal carotid artery, we measured somatosensory evoked
      potential as well as jugular venous oxygen saturation, and used near infrared
      spectophotometry. As a result, postoperative mortality and morbidity were 0% and
      2%, respectively. The candidates for CEA have potentially high perioperative
      risks, and it is important to evaluate the coexisting diseases and to select
      proper anesthetic technic and monitors.

PMID- 9185471
TI  - [Epidural fentanyl provide sufficient analgesia for extracorporeal shock wave
      lithotripsy (ESWL)].
AB  - Epidural fentanyl (0.2 mg in 10 ml normal saline) was administrated in 10
      unpremedicated patients undergoing extracorporeal shock wave lithotripsy (ESWL).
      No test dose of local anesthetics was administrated and accessory drugs such as
      narcotics or analgesics were not used. Painful procedures except for shock wave
      such as insertion of urethral catheter were not applied. We observed analgesic
      effect using original score (grade 0-3) and monitored heart rate, blood pressure,
      respiratory rate and Spo2 during ESWL. At 1, 2, 3, 4 and 24 hours after ESWL,
      patients were questioned regarding the presence of postoperative nausea,
      vomiting, and motor disturbance. At the start of ESWL, nine patients experienced
      mild pain, although no patient requested additional analgesic treatment. Until
      the end of ESWL, local anesthetics were administered through the epidural
      catheter in three patients because of increase of pain, while the others
      completed ESWL with epidural fentanyl alone. No remarkable change in blood
      pressure and heart rate were observed. Respiratory rate and Spo2 slightly
      decreased during ESWL. Postoperative side effects were mild especially in the
      patients treated with epidural fentanyl alone. Epidural fentanyl is considered to
      be useful analgesic technique for ESWL.

PMID- 9185472
TI  - [A patient who recovered successfully from severe anemia which continued for one
      hour].
AB  - A 79-year-old woman had her cervical spinal cord injured and laminoplasty of the
      neck was performed. Uncontrollable venous bleeding was encountered during the
      operation and about 5000 ml of blood was lost in one hour. Massive infusion of 5%
      albumin and hydroxyethylstarch (HES) was done to maintain the intravascular
      volume. Therefore, her hematocrit value (Ht) decreased to 4.5%. Her rectal
      temperature went down to 34.5 degrees C. The operation was finished in haste. We
      studied leg pain experienced under spinal anesthesia in leprosy patients. Seven
      of twenty patients complained of the leg pain a few minutes after spinal block.
      The pain was localized in the parts of deafferentation or phantom limb, and was
      relatively mild and controllable. We consider that the inhibitory system is
      inactivated when the somatic impulse is blocked by spinal anesthesia, and as a
      result the abnormal burst activity of dorsal horn produced by peripheral nerve
      damage of leprosy causes phantom pain.

PMID- 9185473
TI  - [Leg pain under spinal anesthesia in leprosy patients].
AB  - We studied leg pain experienced under spinal anesthesia in leprosy patients.
      Seven of twenty patients complained of the leg pain a few minutes after spinal
      block. The pain was localized in the parts of deafferentation or phantom limb,
      and was relatively mild and controllable. We consider that the inhibitory system
      is inactivated when the somatic impulse is blocked by spinal anesthesia, and as a
      result the abnormal burst activity of dorsal horn produced by peripheral nerve
      damage of leprosy causes phantom pain.

PMID- 9185474
TI  - [Bacterial drug extruding antiporter].

PMID- 9185475
TI  - [Molecular mechanisms for drug transport by MDR1/P-glycoprotein].

PMID- 9185476
TI  - [Role of transporters in the detoxification of xenobiotics: recent advances in
      the study of cMOAT/MRP].

PMID- 9185478
TI  - [Recombinant fibronectin fragments in stem cell gene therapy].

PMID- 9185477
TI  - [The GS X pump family: ATP dependent multispecific organic anion transporters].

PMID- 9185479
TI  - [The protein data bank: recent trends and developments].

PMID- 9185480
TI  - [Molecular imprinting: tailor made synthetic receptors capable of molecular
      recognition].

PMID- 9185481
TI  - [A nested deletion method for cosmid DNA using the bacteriophage T3 in vitro
      packaging system].

PMID- 9185482
TI  - Screening for colorectal cancer.
AB  - Colorectal carcinoma represents a major cause of cancer deaths in the United
      Kingdom. Tumours detected at an early or even premalignant stage have a better
      prognosis. In this review we consider the argument for screening for colorectal
      carcinomas and discuss the means available and the implications of implementing
      screening programmes using some of these methods. A suggestion is made for the
      more rational use of limited resources to target those at greatest risk.

PMID- 9185483
TI  - The Belfast Cord Blood Bank.
AB  - The first cord blood bank in the British Isles was established in Belfast in June
      1993. Cord blood (CB) is rich in haematopoietic progenitor cells and has been
      used successfully as a substitute for bone marrow transplants in over 200
      patients world-wide. Most have received CB from a histocompatible sibling, but
      reports include several unrelated HLA matched transplants. In addition to the
      cryopreservation of 400 units of donated CB in the Cord Blood Bank, we have
      stored eight CB collections from siblings of children with leukaemia in Northern
      Ireland. A pilot study in collaboration with the maternity unit in the Mater
      Infirmorum Hospital confirmed the feasibility of a CB banking programme and
      highlighted many issues relating to Good Manufacturing Practice (GMP). The
      authors describe experience of collecting 824 units of CB over three years and
      discuss a few of the wider implications of this innovation in the management of
      patients requiring myeloablative therapy.

PMID- 9185484
TI  - Nosological Inaccuracies in death certification in Northern Ireland. A
      comparative study between hospital doctors and general practitioners.
AB  - We aimed to audit nosological inaccuracies in death certification in Northern
      Ireland and to compare performance of hospital doctors and general practitioners.
      Nosology is the branch of medicine which treats of the classification of disease.
      1138 deaths were registered in Northern Ireland in a 4-week period commencing
      3/10/94. 195 of these were either registered by HM Coroners (HMC) or required
      further investigation by their staff; these cases were excluded from the study.
      The remaining 943 were analysed for wording and formulation inaccuracies
      according to the revised notes (1974), Northern Ireland Medical Certificate of
      Cause of Death. These are issued in book form by the Registrar of Births and
      Deaths. The commonest inaccuracies in death certification occur in the areas of
      poor terminology, sequence errors and unqualified mode. One or more inaccuracies
      were found in 317 (33.6%) of cases. In 13 of these (4%) cases, the inaccuracies
      were serious enough to warrant referral by the Registrar of Deaths to HM Coroner.
      The numbers of general practitioners and hospital doctors were recorded, with
      general practitioners being responsible for 122 (38%) and hospital doctors being
      responsible for 195 (62%) of inaccuracies.

PMID- 9185485
TI  - A standardised breakfast tolerance test in pregnancy: comparison with the 75 g
      oral glucose tolerance test in unselected mothers and in those with impaired
      glucose tolerance.
AB  - There is still disagreement concerning the optimal procedure for the diagnosis of
      milder degrees of hyperglycaemia in pregnancy. We have compared the results of a
      75 g oral glucose tolerance test (OGTT) and a standardised breakfast test
      performed one week apart in 102 non-diabetic women with a singleton pregnancy.
      There was poor correlation between the two tests (r = 0.15) at two hours, and
      neither test was predictive of adverse maternal or fetal outcome. One hundred and
      four patients with impaired glucose tolerance, diagnosed at 30 weeks' gestation
      by 75 g OGTT, subsequently had a breakfast and lunch meal profile. There was no
      significant correlation between the two-hour OGTT value and either the two hour
      post-breakfast value (r = 0.35) or the maximum profile value (r = 0.33). Using
      the WHO diagnostic criterion of > 8 mmol/l for the OGTT and a maximum glucose
      concentration > 6.8 mmol/l for the meal profile, there was no relationship
      between an abnormal result in either test and pregnancy outcome. In our obstetric
      environment, the 75 g OGTT, a standardised breakfast test, and a structured meal
      profile, all failed to provide a useful indication of pregnancy outcome in
      mothers not already known to have diabetes.

PMID- 9185486
TI  - A 3 year audit of fine needle aspirates from a symptomatic breast clinic.
AB  - A total of 2431 fine needle aspirates of symptomatic breast lumps was performed
      on 2096 patients over the last three years at the weekly head, neck and breast
      clinic at the Belfast City Hospital Trust. Diagnostic accuracy was achieved
      within the recommended standards although the "insufficient" rate was high at
      31.8%. False negative and positive rates were low and the positive predictive
      value for malignancy was 99%. Excision biopsy for benign breast disease had
      decreased by almost a third during this period. Fine needle aspiration cytology
      is a highly accurate and cost-effective technique for the investigation of
      symptomatic breast lumps and results in significant savings.

PMID- 9185487
TI  - Doctors' knowledge of post traumatic neurosis.
AB  - Most studies which looked at the civil disturbances in Northern Ireland for the
      25 years until the ceasefire declarations in late 1994 concluded that the impact
      on the psychological health of the population was insubstantial. In the study
      reported below doctors as a group were quite accurate in identifying the features
      of post traumatic stress disorder (P.T.S.D.) on a questionnaire but there is
      evidence to suggest that post traumatic neurosis has been under recognized in the
      clinical situation and, therefore, undertreated. Improving the accuracy with
      which doctors recognise psychiatric illness in general, and increased awareness
      of P.T.S.D. in particular, may well lead to increasing ability to diagnose the
      condition and thereby provide the individual with the opportunity for treatment.

PMID- 9185488
TI  - Anaesthesia for appendicectomy in childhood: a survey of practice in Northern
      Ireland.
AB  - A postal questionnaire was sent to all members of the Northern Ireland Society of
      Anaesthetists to determine current practice in anaesthesia for children with
      acute appendicitis. Respondents were asked to describe their usual practice in
      such cases. They were also asked about the occurrence of complications due to the
      use of suxamethonium, and for their views on the use of rocuronium in such cases.
      Few major differences in anaesthetic technique were demonstrated. 74% of
      consultants and 84% of trainees always perform a rapid sequence induction for
      appendicectomy. However 15% of consultants do not feel that this is necessary.
      Only 6% of consultants and 6% of trainees would normally use rocuronium, with the
      majority still preferring suxamethonium. Only 28% of consultants and 20% of
      trainees see rocuronium as a possible alternative to suxamethonium in these
      cases, although others expressed increasing concern over the use of suxamethonium
      in children. There was wide variation in the type of intra-operative and post
      operative analgesia prescribed, with less than one third of consultants and
      trainees using combinations of opioids, local anaesthetics and non-steroidal anti
      inflammatory drugs.

PMID- 9185489
TI  - Change in the use of and attitude to peak flow measurement among general
      practitioners in Northern Ireland between 1989 and 1994.
AB  - In 1994 we repeated a study first performed in 1989 to assess the change in
      general practitioners' use of and attitudes to peak flow measurement. Of 232
      general practitioners surveyed, 199 (86%) and 192 (83%) responded in 1989 and
      1994 respectively. The percentage who reported having patients using domiciliary
      peak flow monitoring rose form 58.3 (95% confidence limits 51.4 to 65.2)% to 97.9
      (95.9 to 99.9)%. The percentage who reported 'usually' using peak flow
      measurements for the diagnosis and management of asthma rose from 81.9 (76.5 to
      87.3)% to 93.2 (89.6 to 96.8)% and from 83.3 (78.1 to 88.5)% to 95.8 (92.9 to
      98.7)% respectively. An unchanged proportion took peak flow meters on house
      calls. General practitioners have become more aware of the potential of peak flow
      measurements but are still unlikely to have a meter available to assess patients
      seen at home. They are therefore likely to be ill-equipped to manage acute
      exacerbations of asthma in this setting.

PMID- 9185490
TI  - Health and education--the metabolism of a teaching hospital.

PMID- 9185491
TI  - Mixed sex-cord stromal tumour of the testis.

PMID- 9185492
TI  - Hypercholesterolaemia in a vegan.

PMID- 9185493
TI  - Coexistence of cystic fibrosis and phenylketonuria.

PMID- 9185494
TI  - Rhesus haemolytic disease of the newborn, complicating a quadruplet pregnancy.

PMID- 9185495
TI  - Expanded programme on immunization (EPI).

PMID- 9185496
TI  - Analysis of the sociodemography of gonorrhoea in Leeds, 1989-93.
AB  - OBJECTIVE: To investigate the epidemiology of gonorrhoea in an urban area in the
      United Kingdom. DESIGN: Analysis of all cases of gonorrhoea with regard to age,
      sex, ethnic group, and socioeconomic group with 1991 census data as a
      denominator. SETTING: Leeds, a comparatively large urban area (population around
      700,000) in the United Kingdom. SUBJECTS: All residents of Leeds with culture
      proved cases of gonorrhoea during 1989-95. MAIN OUTCOME MEASURE: Relative risk of
      gonorrhoea. RESULTS: Sex, age, race, and socioeconomic group and area of
      residence were all independently predictive of risk of infection. Young black men
      aged 20-29 were at highest risk, with incidences of 3-4% per year. Black subjects
      were 10 times more likely than white subjects to acquire infection, and subjects
      from the most deprived socioeconomic areas were more than four times more likely
      than those from the most affluent areas to acquire infection. CONCLUSIONS:
      Different ethnic and socioeconomic groups vary in their risk of infection with
      gonorrhoea within an urban area. Targeted interventions and screening to reduce
      the incidence of sexually transmitted disease are now priorities.

PMID- 9185497
TI  - Gonorrhoea in inner London: results of a cross sectional study.
AB  - OBJECTIVES: To estimate population based incidence rates of gonorrhoea in an
      inner London area and examine relations with age, ethnic group, and socioeconomic
      deprivation. DESIGN: Cross sectional study. SETTING: 11 departments of
      genitourinary medicine in south and central London. SUBJECTS: 1978 first episodes
      of gonorrhoea diagnosed in 1994 and 1995 in residents of 73 electoral wards in
      the boroughs of Lambeth, Southwark, and Lewisham who attended any of the
      departments of genitourinary medicine. MAIN OUTCOME MEASURES: Yearly age, sex,
      and ethnic group specific rates of gonorrhoea per 100,000 population aged 15-59
      years; rate ratios for the effects of age and ethnic group on gonorrhoea rates in
      women and men before and after adjustment for confounding factors. RESULTS:
      Overall incidence rates of gonorrhoea in residents of Lambeth, Southwark, and
      Lewisham were 138.3 cases yearly per 100,000 women and 291.9 cases yearly per
      100,000 men aged 15-59 years. At all ages gonorrhoea rates were higher in non
      white minority ethnic groups. Rate ratios for the effect of age adjusted for
      ethnic group and underprivilege were 15.2 (95% confidence interval 11.6 to 19.7)
      for women and 2.0 (1.7 to 2.5) for men aged 15-19 years compared with those over
      30. After deprivation score and age were taken into account, women from black
      minority groups were 10.5 (8.6 to 12.8) times as likely and men 11.0 (9.7 to
      12.6) times as likely as white people to experience gonorrhoea. CONCLUSIONS:
      Gonorrhoea rates in Lambeth, Southwark, and Lewisham in 1994-5 were six to seven
      times higher than for England and Wales one year earlier. The presentation of
      national trends thus hides the disproportionate contribution of ongoing endemic
      transmission in the study area. Teenage women and young adult men, particularly
      those from black minority ethnic groups, are the most heavily affected, even when
      socioeconomic underprivilege is taken into account. There is urgent need for
      resources for culturally appropriate research and effective intervention to
      prevent gonococcal infections and their long term sequelae in this population.

PMID- 9185498
TI  - Poverty or income inequality as predictor of mortality: longitudinal cohort
      study.
AB  - OBJECTIVE: To determine the effect of inequality in income between communities
      independent of household income on individual all cause mortality in the United
      States. DESIGN: Longitudinal cohort study. SUBJECTS: A nationally representative
      sample of 14,407 people aged 25-74 years in the United States from the first
      national health and nutrition examination survey. SETTING: Subjects were followed
      from initial interview in 1971-5 until 1987. Complete follow up information was
      available for 92.2% of the sample. MAIN OUTCOME MEASURES: Relation between both
      household income and income inequality in community of residence and individual
      all cause mortality at follow up was examined with Cox proportional hazards
      survival analysis. RESULTS: Community income inequality showed a significant
      association with subsequent community mortality, and with individual mortality
      after adjustment for age, sex, and mean income in the community of residence.
      After adjustment for individual household income, however, the association with
      mortality was lost. CONCLUSIONS: In this nationally representative American
      sample, family income, but not community income inequality, independently
      predicts mortality. Previously reported ecological associations between income
      inequality and mortality may reflect confounding between individual family income
      and mortality.

PMID- 9185499
TI  - The clinical investigator: bewitched, bothered, and bewildered--but still
      beloved.

PMID- 9185500
TI  - Interleukin-1 receptor antagonist: a "novel" acute phase protein with
      antiinflammatory activities.

PMID- 9185501
TI  - Perspectives series: cell adhesion in vascular biology. Smooth muscle migration
      in atherosclerosis and restenosis.

PMID- 9185502
TI  - Perspectives series: host/pathogen interactions. Mechanisms of nitric oxide
      related antimicrobial activity.

PMID- 9185503
TI  - A homozygous mutation in the integrin alpha6 gene in junctional epidermolysis
      bullosa with pyloric atresia.
AB  - The alpha6 integrin subunit participates in the formation of both alpha6beta1 and
      alpha6beta4 laminin receptors, which have been reported to play an important role
      in cell adhesion and migration and in morphogenesis. In squamous epithelia, the
      alpha6beta4 heterodimer is the crucial component for the assembly and stability
      of hemidesmosomes. These anchoring structures are ultrastructurally abnormal in
      patients affected with junctional epidermolysis bullosa with pyloric atresia (PA
      JEB), a recessively inherited blistering disease of skin and mucosae
      characterized by an altered immunoreactivity with antibodies specific to integrin
      alpha6beta4. In this report, we describe the first mutation in the alpha6
      integrin gene in a PA-JEB patient presenting with generalized skin blistering,
      aplasia cutis, and defective expression of integrin alpha6beta4. The mutation
      (791delC) is a homozygous deletion of a single base (C) leading to a frameshift
      and a premature termination codon that results in a complete absence of alpha6
      polypeptide. We also describe the DNA-based prenatal exclusion of the disease in
      this family at risk for recurrence of PA-JEB. Our results demonstrate that,
      despite the widespread distribution of the alpha6 integrin subunit, lack of
      expression of the alpha6 integrin chain is compatible with fetal development, and
      results in a phenotype indistinguishable from that caused by mutations in the
      beta4 chain, which is expressed in a more limited number of tissues.

PMID- 9185504
TI  - MCP-1 protects mice in lethal endotoxemia.
AB  - The overzealous production of proinflammatory cytokines in sepsis can result in
      shock, multiorgan dysfunction, and even death. In this study, we assessed the
      role of monocyte chemoattractant protein-1 (MCP-1) as a mediator of sepsis in
      endotoxin-challenged mice. Intraperitoneal administration of LPS to CD-1 mice
      induced a substantial time-dependent increase in MCP-1 in plasma, lung, and
      liver. The passive immunization of mice with rabbit antimurine MCP-1 antiserum 2
      h before endotoxin administration resulted in a striking increase in LPS-induced
      mortality from 10% in control animals to 65% in anti-MCP-1-treated animals.
      Importantly, the administration of anti-MCP-1 antibodies to endotoxin-challenged
      mice resulted in increases in peak TNF-alpha and IL-12 levels, and also in a
      trend toward decreased serum levels of IL-10. Conversely, the administration of
      recombinant murine MCP-1 intraperitoneally significantly protected mice from
      endotoxin-induced lethality, and resulted in an increase in IL-10 levels, a
      decrease in IL-12 levels, and a trend toward decreased levels of TNF. In
      conclusion, our findings indicate that MCP-1 is a protective cytokine expressed
      in murine endotoxemia, and does so by shifting the balance in favor of
      antiinflammatory cytokine expression in endotoxin-challenged animals.

PMID- 9185505
TI  - Inhibition of murine embryonic growth by human immunodeficiency virus envelope
      protein and its prevention by vasoactive intestinal peptide and activity
      dependent neurotrophic factor.
AB  - Intrauterine growth retardation and neurodevelopmental handicaps are common among
      infants born to HIV-positive mothers and may be due to the actions of virions
      and/or maternally derived viral products. The viral envelope protein, gp120, is
      toxic to neurons, induces neuronal dystrophy, and retards behavioral development
      in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of
      early postimplantation embryonic growth, and the neuroprotective protein,
      activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity.
      Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the
      effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent
      inhibition of growth. gp120-treated embryos (10(-8) M) grew 1.2 somites in the 6
      h incubation period, compared with 3.9 somites by control embryos. Embryos
      treated with gp120 were significantly smaller in cross-sectional area and had
      significantly less DNA and protein than controls. Growth inhibition induced by
      gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity
      dependent neurotrophic factor. gp120 may play a role in the growth retardation
      and developmental delays experienced by infants born to HIV-positive mothers.
      Vasoactive intestinal peptide and related factors may provide a therapeutic
      strategy in preventing developmental deficits.

PMID- 9185506
TI  - Glucocorticoid-mediated repression of cytokine gene transcription in human
      arteritis-SCID chimeras.
AB  - Giant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects
      medium and large-sized arteries. Glucocorticoid therapy resolves clinical
      symptoms within hours to days, but therapy has to be continued over several years
      to prevent disease relapses. It is not known whether and how glucocorticoids
      affect the function of the inflammatory infiltrate or why the disease persists
      subclinically despite chronic treatment. GCA is self-sustained in temporal
      arteries engrafted into SCID mice, providing a model in which the mechanisms of
      action and limitations of glucocorticoid therapy can be examined in vivo.
      Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced
      a partial suppression of T cell and macrophage function as indicated by the
      reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the
      diminished expression of inducible NO synthase. In contrast, synthesis of IFN
      gamma mRNA was only slightly decreased, and expression of TGF-beta1 was
      unaffected. These findings correlated with activation of the IkappaBalpha gene
      and blockade of the nuclear translocation of NFkappaB in the xenotransplanted
      tissue. Dose-response experiments suggested that steroid doses currently used in
      clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine
      production in the inflammatory lesions. Chronic steroid therapy was able to
      deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue
      infiltrating macrophages was only partially affected. IL-1beta transcription was
      abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant. The
      persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell
      function, may provide an explanation for the chronicity of the disease, and may
      identify a novel therapeutic target in this inflammatory vasculopathy.

PMID- 9185507
TI  - Suppression of matrix metalloproteinases inhibits establishment of ectopic
      lesions by human endometrium in nude mice.
AB  - Matrix metalloproteinases of the stromelysin family are expressed in the human
      endometrium as a consequence of cellular events during the menstrual cycle that
      require extracellular matrix remodeling. We have recently documented the presence
      of these enzymes in lesions of endometriosis, a benign disease that presents as
      persistent ectopic sites of endometrial tissue, usually within the peritoneal
      cavity. Endometriosis can develop after retrograde menstruation of endometrial
      tissue fragments, and establishment of ectopic sites within the peritoneal cavity
      requires breakdown of extracellular matrix. To examine whether matrix
      metalloproteinases might contribute to the steroid-dependent epidemiology and
      cellular pathophysiology of endometriosis, we have developed an experimental
      model of endometriosis using athymic nude mice as recipients of human endometrial
      tissue. Our results demonstrate that estrogen treatment of human endometrial
      tissue in organ culture maintains secretion of matrix metalloproteinases, and
      promotes establishment of ectopic peritoneal lesions when injected into recipient
      animals. In contrast, suppressing metalloproteinase secretion in vitro with
      progesterone treatment, or blocking enzyme activity with a natural inhibitor of
      metalloproteinases, inhibits the formation of ectopic lesions in this
      experimental model.

PMID- 9185508
TI  - Paradoxical enhancement of atherosclerosis by probucol treatment in
      apolipoprotein E-deficient mice.
AB  - Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma
      cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with
      decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%,
      respectively. Paradoxically, however, aortic atherosclerotic plaques in the
      probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/-
      mice, and the lesions were two to four times larger and more mature regardless of
      sex, age, and genetic background (P < 10(-)6). Histologically, lesions in
      probucol-treated mice contained increased fibrous materials and cells other than
      foam cells, and were commonly associated with focal inflammation and aneurysmal
      dilatation. Probucol treatment also accelerated lesion development in apoE+/-
      mice fed an atherogenic diet, indicating that the adverse effect is not dependent
      on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have
      plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice,
      but do not have accelerated plaque development. Thus, the enhanced
      atherosclerosis in the probucol-treated animals is unlikely to be caused by the
      reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma
      cholesterol caused by probucol does not necessarily lead to an antiatherogenic
      effect.

PMID- 9185510
TI  - Excessive formation of hydroxyl radicals and aldehydic lipid peroxidation
      products in cultured skin fibroblasts from patients with complex I deficiency.
AB  - Previous studies suggest oxygen free radicals' involvement in the etiology of
      cardiomyopathy with cataracts. To investigate the role of free radicals in the
      pathogenesis of the cardiomyopathy with cataracts and complex I deficiency,
      fibroblasts from patients were assessed for hydroxyl radical formation and
      aldehydic lipid peroxidation products with and without redox active agents that
      increase free radicals. The rate of hydroxyl radical formation in patient cells
      was increased over 2-10-fold under basal conditions, and up to 20-fold after
      menadione or doxorubicin treatment compared with normal cells. We also found an
      overproduction of aldehydes in patient cells both under basal conditions and
      after treatment. Both hydroxyl radicals and toxic aldehydes such as hexanal, 4
      hydroxynon-2-enal, and malondialdehyde were elevated in cells from patients with
      three types of complex I deficiency. In contrast, acyloins, the less toxic
      conjugated products of pyruvate and saturated aldehydes, were lower in the
      patient cells. Our data provide direct evidence for the first time that complex I
      deficiency is associated with excessive production of hydroxyl radicals and lipid
      peroxidation. The resultant damage may contribute to the early onset of
      cardiomyopathy and cataracts and death in early infancy in affected patients with
      this disease.

PMID- 9185509
TI  - Aortic endothelial cells regulate proliferation of human monocytes in vitro via a
      mechanism synergistic with macrophage colony-stimulating factor. Convergence at
      the cyclin E/p27(Kip1) regulatory checkpoint.
AB  - Monocyte-derived macrophages (Mphis) are pivotal participants in the pathogenesis
      of atherosclerosis. Evidence from both animal and human plaques indicates that
      local proliferation may contribute to accumulation of lesion Mphis, and the major
      Mphi growth factor, macrophage colony stimulating factor (MCSF), is present in
      atherosclerotic plaques. However, most in vitro studies have failed to
      demonstrate that human monocytes/Mphis possess significant proliferative
      capacity. We now report that, although human monocytes cultured in isolation
      showed only limited MCSF-induced proliferation, monocytes cocultured with aortic
      endothelial cells at identical MCSF concentrations underwent enhanced (up to 40
      fold) and prolonged (21 d) proliferation. In contrast with monocytes in
      isolation, this was optimal at low seeding densities, required endothelial cell
      contact, and could not be reproduced by coculture with smooth muscle cells.
      Intimal Mphi isolated from human aortas likewise showed endothelial cell contact
      dependent, MCSF-induced proliferation. Consistent with a two-signal mechanism
      governing Mphi proliferation, the cell cycle regulatory protein, cyclin E, was
      rapidly upregulated by endothelial cell contact in an MCSFindependent fashion,
      but MCSF was required for successful downregulation of the cell cycle inhibitory
      protein p27(Kip1) before cell cycling. Thus endothelial cells and MCSF
      differentially and synergistically regulate two Mphi genes critical for
      progression through the cell cycle.

PMID- 9185511
TI  - Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance
      in rats.
AB  - Wistar rats develop glucose intolerance and have a diminished insulin response to
      glucose with age. The aim of this study was to investigate if these changes were
      reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have
      previously shown could increase insulin mRNA and total insulin content in
      insulinoma cells. We infused 1.5 pmol/ kg-1.min-1 GLP-1 subcutaneously using
      ALZET microosmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with
      either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg
      body weight) tolerance test, 2 h after removing the pump. 15 min after the
      intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels
      (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23
      mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated
      animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/
      0.43 mmol/liter). This decrease in glucose levels was reflected in the higher
      insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs.
      395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min
      after glucose injection. GLP-1 treatment also increased pancreatic insulin,
      GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished
      by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1
      is therefore able to reverse some of the known defects that arise in the beta
      cell of the pancreas of Wistar rats, not only by increasing insulin secretion but
      also by inducing significant changes at the molecular level.

PMID- 9185512
TI  - Cytosolic Ca2+ and protein kinase Calpha couple cellular metabolism to membrane
      K+ permeability in a human biliary cell line.
AB  - Cholangiocytes represent an important target of injury during the ischemia and
      metabolic stress that accompanies liver preservation. Since K+ efflux serves to
      minimize injury during ATP depletion in certain other cell types, the purpose of
      these studies was to evaluate the effects of ATP depletion on plasma membrane K+
      permeability of Mz-ChA-1 cells, a model human biliary cell line. Cells were
      exposed to dinitrophenol (50 microM) and 2-deoxyglucose (10 mM) as the standard
      model of metabolic injury. Whole-cell and single K+ channel currents were
      measured using patch clamp techniques; and intracellular [Ca2+] ([Ca2+]i) was
      estimated by calcium green-1 fluorescence. Metabolic stress increased [Ca2+]i,
      and stimulated translocation of the alpha isoform of protein kinase C (PKCalpha)
      from cytosolic to particulate cell fractions. The same maneuver increased
      membrane K+ permeability 40-70-fold as detected by (a) activation of K+selective
      whole cell currents of 2,176+/-218 pA (n = 34), and (b) opening of apamin
      sensitive K+ channels with a unitary conductance of 17.0+/-0.2 pS. PKCalpha
      translocation and channel opening appear to be related since stress-induced K+
      efflux is inhibited by chelation of cytosolic Ca2+, exposure to the PKC inhibitor
      chelerythrine (25 microM) and downregulation of PKC by phorbol esters. Moreover,
      K+ currents were activated by intracellular perfusion with recombinant PKCalpha
      in the absence of metabolic inhibitors. These findings indicate that in biliary
      cells apamin-sensitive K+ channels are functionally coupled to cell metabolism
      and suggest that cytosolic Ca2+ and PKCalpha are selectively involved in the
      response.

PMID- 9185513
TI  - Signals through gp130 upregulate bcl-x gene expression via STAT1-binding cis
      element in cardiac myocytes.
AB  - We described recently the activation of the Janus kinasesignal transducer and
      activator of transcription (JakSTAT) and mitogen-activated protein (MAP) kinase
      pathways by leukemia inhibitory factor (LIF) through gp130, a signal transducer
      of IL-6-related cytokines, that transduces hypertrophic signals in cardiac
      myocytes. In addition, stimulation of gp130 by IL-6-related cytokines is known to
      exert a cytoprotective effect. In the present study, we investigated the
      possibility that activation of gp130 initiates activation of the cytoprotective
      genes in cardiac myocytes. Incubation of cardiac myocytes with LIF induced the
      expression of bcl-x, and the isoform that was induced by LIF was identified as
      bcl-xL. Induction of bcl-xL protein was also identified by Western blotting.
      Antisense oligonucleotide against bcl-x mRNA inhibited protective effect of LIF
      accompanied with the reduction in bclxL protein. We constructed bcl-x promoter
      luciferase reporter gene plasmids (-639/+10- or -161/+10-luciferase), and
      transfected them to cardiac myocytes. LIF stimulation increased the luciferase
      activity of -639/+10-luciferase plasmids. Although -161/+10-luciferase plasmids
      presented comparable responsiveness to LIF, the basal transcription level was
      impaired. The LIF-responsive cis-element was localized to a DNA fragment
      (positions -161 to +10) that contains an interferon-gamma activation site (GAS)
      motif (GGA) at position -41 of the bcl-x gene promoter. This motif bound to
      STAT1, not to STAT3, and site-directed mutagenesis revealed that this motif was
      essential for LIF-responsive promoter activity. These data suggest that LIF
      induces bcl-x mRNA via STAT1 binding cis-element in cardiac myocytes, presenting
      cytoprotective effect.

PMID- 9185514
TI  - Regulation of the rat liver sodium-dependent bile acid cotransporter gene by
      prolactin. Mediation of transcriptional activation by Stat5.
AB  - The intracellular mechanism(s) underlying the upregulation of the hepatic
      Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are
      unknown. In this report, we demonstrate a time-dependent increase in nuclear
      translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and
      ctivators of ranscription family) that correlated with suckling-induced increases
      in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5
      exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)
      like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp
      region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed
      that PRL inducibility (2.5-3-fold) required coexpression of the long form of the
      PRL receptor (PRLRL) and Stat5. Deletion analysis mapped the PRLinducible region
      to -1237 to -758 bp of the ntcp promoter. Linking this 0.5-kb region to a
      heterologous thymidine kinase (tk) promoter, or linking multimerized ntcp GLEs
      either upstream of the ntcp minimal promoter (-158 to +47 bp) or the heterologous
      promoter conferred dose-dependent PRL responsiveness. The short form of the PRL
      receptor failed to transactivate ntcp GLEs. These results indicate that PRL acts
      via the PRLRL to facilitate Stat5 binding to ntcp-GLEs and to transcriptionally
      regulate ntcp.

PMID- 9185515
TI  - Leukotriene D4 activates a chloride conductance in hepatocytes from
      lipopolysaccharide-treated rats.
AB  - Endotoxin (LPS) can cause hepatocellular injury under several circumstances, and
      leukotrienes have been implicated as a contributing factor. Since ion channel
      activation has been associated with cytotoxicity, the aim of this study was to
      determine the circumstances under which LPS and/or leukotrienes activate ionic
      conductances in hepatocytes. LPS treatment of rats increased Cl- conductance in
      hepatocytes from 232+/-42 to 1236+/-134 pS/pF. Voltage dependence and inhibitor
      specificity of this conductance were similar to that of a swelling-activated Cl-
      conductance, and internal dialysis with nucleoside analogues suggested control by
      an inhibitory G protein. The lipoxygenase inhibitor nordihydroguaiaretic acid,
      the specific leukotriene D4 (LTD4) receptor antagonist MK-571, and the 5
      lipoxygenase activating protein inhibitor MK-886 all significantly inhibited the
      conductance. Intracellular dialysis with LTD4 (1.5 microM) elevated intracellular
      Ca2+ from 143+/-6.5 to 388+/-114 nM within 6 min and stimulated an outwardly
      rectifying conductance from 642+/-159 to 1669+/-224 pS/pF (n = 9, P < 0.001). In
      hepatocytes prepared from untreated rats, this concentration of intracellular
      LTD4 neither raised intracellular Ca2+ nor activated the conductance. The LTD4
      response could be induced in normal hepatocytes by culture with either
      conditioned medium from LPS-treated macrophages or purified TNF-alpha. In
      conclusion, intracellular LTD4 activates a chloride conductance in hepatocytes
      isolated from rats treated with LPS or primed in vitro with TNF-alpha. Changes in
      the hepatocellular accumulation of leukotrienes therefore mediate channel
      activation and may contribute to liver injury during sepsis and other
      inflammatory conditions.

PMID- 9185516
TI  - Impaired diurnal adrenal rhythmicity restored by constant infusion of
      corticotropin-releasing hormone in corticotropin-releasing hormone-deficient
      mice.
AB  - The normal pattern of daily glucocorticoid production in mammals requires
      circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess
      both the factors responsible for imparting this diurnal profile and its
      physiologic importance, we have exploited corticotropin-releasing hormone (CRH)
      deficient mice generated by homologous recombination in embryonic stem cells. CRH
      deficient mice have lost normal circadian variations in plasma ACTH and
      glucocorticoid while maintaining normal circadian locomotor activity. Constant
      peripheral infusion of CRH produced marked diurnal excursions of plasma
      glucocorticoid, indicating that CRH acts in part as a permissive factor for other
      circadian modulators of adrenocortical activity. The presence of atrophic
      adrenals in CRH-deficient mice without an overt deficit in basal plasma ACTH
      concentration suggests that the diurnal increase in ACTH is essential to maintain
      normal adrenal function.

PMID- 9185517
TI  - Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein.
AB  - Interleukin 1 receptor antagonist (IL-1Ra) levels are elevated in the blood of
      patients with a variety of infectious, immune, or traumatic conditions. To
      examine whether IL1Ra is produced by liver cells with characteristics resembling
      an acute-phase protein, human primary hepatocytes isolated from liver biopsies
      and HepG2 hepatoma cells were stimulated with IL-1beta, IL-6, and TNFalpha. IL
      1Ra was present in the supernatants of both cells, with production significantly
      enhanced by IL-1beta, and by the combination of IL-1beta and IL-6. The term IL
      1Ra refers to two different proteins encoded by the same gene, but generated by
      alternative splicing of two different first exons. One isoform is secreted (17-kD
      sIL-1Ra), and the other isoform remains in the cytoplasm (18-kD icIL-1Ra). By
      Western blot analysis, the supernatants of human hepatoma (HepG2) cells contained
      only sIL-1Ra, whereas the lysates contained a novel smaller molecular mass
      isoform of 16 kD. RT-PCR and ribonuclease protection assay with RNA from HepG2
      cells showed that only sIL-1Ra mRNA was expressed, and confirmed the inducing
      effect of IL-1beta and IL-6. Transfection studies were performed using constructs
      containing the promoters of either sIL-1Ra or icIL-1Ra coupled to the luciferase
      reporter gene. The sIL-1Ra promoter was active in HepG2 cells stimulated by IL
      1beta and/or IL-6, whereas the icIL-1Ra promoter was inactive. Mutation of
      binding sites for transcription factors NF-kappaB and/or C/EBP within the
      proximal sIL-1Ra promoter led to significant decreases in response to IL-1beta
      and IL-6 in comparison to the wild-type promoter. Electromobility gel shift
      assays confirmed the presence of NF-kappaB and C/EBP binding sites within the sIL
      1Ra promoter, and indicated a significant increase in the binding activities of
      nuclear proteins from HepG2 cells treated with IL-1beta and IL-6. In summary, sIL
      1Ra, but not icIL-1Ra, is produced by hepatocytes, and is regulated by
      proinflammatory cytokines as an acute-phase protein. In addition, NF-kappaB and
      C/EBP family members are likely to play important roles in the full expression of
      IL-1Ra by hepatocytes during inflammatory conditions.

PMID- 9185518
TI  - Expression of the bumetanide-sensitive Na-K-Cl cotransporter BSC2 is
      differentially regulated by fluid mechanical and inflammatory cytokine stimuli in
      vascular endothelium.
AB  - In vascular endothelium, the electroneutral Na-K-Cl cotransport system is thought
      to function in the maintenance of a selective permeability barrier in certain
      vascular beds (e.g., brain), as well as in the preservation of endothelial
      homeostasis in the face of fluctuating osmotic conditions that may accompany
      certain pathophysiological conditions (e.g., diabetes mellitus). Here we
      demonstrate that the gene encoding the bumetanide-sensitive cotransporter BSC2,
      one of the two major isoforms of Na-K-Cl cotransporters present in mammalian
      cells, can be differentially regulated by inflammatory cytokines and fluid
      mechanical forces in cultured endothelium. Interleukin-1beta and tumor necrosis
      factor-alpha significantly upregulate expression of BSC2 mRNA and protein in
      human umbilical vein endothelial cells, a response that is inhibited by
      pretreatment with interferon-gamma. Steady laminar fluid shear stress, at a
      physiologic magnitude (10 dyn/cm2), is also able to induce and maintain elevated
      expression of BSC2 in cultured human umbilical vein endothelial cells, while a
      comparable time-averaged magnitude of turbulent fluid shear stress is not. In
      vivo, BSC2 mRNA is upregulated after intraperitoneal administration of bacterial
      endotoxin (LPS) in murine lung and kidney, but not in cardiac tissue. These
      results provide the first experimental evidence that the BSC2 gene can be
      selectively regulated by different inflammatory cytokine and fluid mechanical
      stimuli in endothelium, and support a role for BSC2 in vascular homeostasis and
      inflammation.

PMID- 9185519
TI  - The role of transglutaminase in the rat subtotal nephrectomy model of renal
      fibrosis.
AB  - Tissue transglutaminase is a calcium-dependent enzyme that catalyzes the cross
      linking of polypeptide chains, including those of extracellular matrix (ECM)
      proteins, through the formation of epsilon-(gamma-glutamyl) lysine bonds. This
      crosslinking leads to the formation of protein polymers that are highly resistant
      to degradation. As a consequence, the enzyme has been implicated in the
      deposition of ECM protein in fibrotic diseases such as pulmonary fibrosis and
      atherosclerosis. In this study, we have investigated the involvement of tissue
      transglutaminase in the development of kidney fibrosis in adult male Wistar rats
      submitted to subtotal nephrectomy (SNx). Groups of six rats were killed on days
      7, 30, 90, and 120 after SNx. As previously described, these rats developed
      progressive glomerulosclerosis and tubulo-interstitial fibrosis. The tissue level
      of epsilon-(gamma-glutamyl) lysine cross-link (as determined by exhaustive
      proteolytic digestion followed by cation exchange chromatography) increased from
      3.47+/- 0.94 (mean+/-SEM) in controls to 13.24+/-1.43 nmol/g protein 90 d after
      SNx, P </= 0.01. Levels of epsilon-(gamma-glutamyl) lysine cross-link correlated
      well with the renal fibrosis score throughout the 120 observation days (r = 0.78,
      P </= 0.01). Tissue homogenates showed no significant change in overall
      transglutaminase activity (14C putrescine incorporation assay) unless adjusted
      for the loss of viable tubule cells, when an increase from 5.77+/-0.35 to 13.93+/
      4.21 U/mg DNA in cytosolic tissue transglutaminase activity was seen. This
      increase was supported by Western blot analysis, showing a parallel increase in
      renal tissue transglutaminase content. Immunohistochemistry demonstrated that
      this large increase in epsilon-(gamma-glutamyl) lysine cross-link and tissue
      transglutaminase took place predominantly in the cytoplasm of tubular cells,
      while immunofluorescence also showed low levels of the epsilon-(gamma-glutamyl)
      lysine cross-link in the extracellular renal interstitial space. The number of
      cells showing increases in tissue transglutaminase and its cross-link product,
      epsilon-(gamma-glutamyl) lysine appeared greater than those showing signs of
      typical apoptosis as determined by in situ end-labeling. This observed
      association between tissue transglutaminase, epsilon-(gamma-glutamyl) lysine
      cross-link, and renal tubulointerstitial scarring in rats submitted to SNx
      suggests that tissue transglutaminase may play an important role in the
      development of experimental renal fibrosis and the associated loss of tubule
      integrity.

PMID- 9185520
TI  - Parathyroid hormone exerts disparate effects on osteoblast differentiation
      depending on exposure time in rat osteoblastic cells.
AB  - It has been reported that PTH exerts bone-forming effects in vivo when
      administered intermittently. In the present study, the anabolic effects of PTH(1
      34) on osteoblast differentiation were examined in vitro. Osteoblastic cells
      isolated from newborn rat calvaria were cyclically treated with PTH(1-34) for the
      first few hours of each 48-h incubation cycle. When osteoblastic cells were
      intermittently exposed to PTH only for the first hour of each 48-h incubation
      cycle and cultured for the remainder of the cycle without the hormone, osteoblast
      differentiation was inhibited by suppressing alkaline phosphatase activity, bone
      nodule formation, and mRNA expression of alkaline phosphatase, osteocalcin, and
      PTH/PTHrP receptor. Experiments using inhibitors and stimulators of cAMP/protein
      kinase A (PKA) and Ca2+/PKC demonstrated that cAMP/PKA was the major signal
      transduction system in the inhibitory action of PTH. In contrast, the
      intermittent exposure to PTH for the first 6 h of each 48-h cycle stimulated
      osteoblast differentiation. Both cAMP/ PKA and Ca2+/PKC systems appeared to be
      involved cooperatively in this anabolic effect. Continuous exposure to PTH during
      the 48-h incubation cycle strongly inhibited osteoblast differentiation. Although
      both cAMP/PKA and Ca2+/PKC were involved in the effect of continuous exposure to
      PTH, they appeared to act independently. A neutralizing antibody against IGF-I
      blocked the stimulatory effect on alkaline phosphatase activity and the
      expression of osteocalcin mRNA induced by the 6-h intermittent exposure. The
      inhibitory effect induced by the 1-h intermittent exposure was not affected by
      anti-IGF-I antibody. These results suggest that PTH has diverse effects on
      osteoblast differentiation depending on the exposure time in vitro mediated
      through different signal transduction systems. These in vitro findings explain at
      least in part the in vivo action of PTH that varies with the mode of
      administration.

PMID- 9185521
TI  - In situ polymerase chain reaction-based localization studies support role of
      human herpesvirus-8 as the cause of two AIDS-related neoplasms: Kaposi's sarcoma
      and body cavity lymphoma.
AB  - Several lines of investigation point to a new herpesvirus, human herpesvirus-8
      (HHV-8), as the cause of two different neoplasms seen in AIDS patients-Kaposi's
      sarcoma (KS) and body cavity B cell lymphoma. If this virus is the etiological
      agent, rather than another opportunistic infectious agent, it should be present
      in the earliest detectable clinical lesions on a temporal basis, and localize to
      specific target cells in a spatial pattern consistent with tumorigenic pathways.
      In this study, we take advantage of the clinical accessibility to biopsy early
      (patch stage) skin lesions of KS to address the temporal issue, combined with in
      situ PCR and dual immunostaining using a marker identifying malignant cells, to
      address the spatial localization issue. 21 different tissue samples were
      subjected to PCR analysis and in situ PCR with and without simultaneous
      immunostaining. In normal skin from healthy individuals, no HHV-8 DNA was
      detected by PCR or in situ PCR. However, in all PCR-positive tissues, distinct
      and specific in situ PCR staining was observed. In four different patch stage KS
      lesions, in situ PCR staining localized to nuclei of endothelial cells and
      perivascular spindle-shaped tumor cells. Later stage KS lesions (plaques and
      nodules) revealed additional positive cells, including epidermal keratinocytes
      (four of five), and eccrine epithelia (two of four). These patterns were
      nonrestricted to skin, as pulmonary KS also revealed HHV-8-specific infection of
      endothelial cells and KS tumor cells, as well as epithelioid pneumocytes (two of
      two). In body cavity B cell lymphoma by dual staining, HHV-8 was present in
      malignant tumor cells (EMA immunostained positive) and not in reactive
      lymphocytes. These results reveal an early temporal onset and nonrandom tissue
      and cellular distribution pattern for HHV-8 infection that is consistent with a
      causal link between this DNA virus and two AIDS-related neoplasms.

PMID- 9185523
TI  - Intraamniotic interleukin-1 accelerates surfactant protein synthesis in fetal
      rabbits and improves lung stability after premature birth.
AB  - Intraamniotic infection is associated with increased IL-1 activity in amniotic
      fluid, increased incidence of preterm labor, and with decreased incidence of
      respiratory distress syndrome in infants born prematurely. We hypothesized that
      an elevated IL-1 in amniotic fluid promotes fetal lung maturation. On day 23 or
      25 of gestation (term 31 d), either IL-1alpha (150 or 1,500 ng per fetus) or its
      antagonist IL-1 receptor antagonist (IL-1ra, 20 microg) was injected to the
      amniotic fluid sacs in one uterine horn, whereas the contralateral amniotic sacs
      were injected with vehicle. Within 40 h, IL-1alpha caused a dose-dependent
      increase in surfactant protein-A (SP-A) and SP-B mRNAs (maximally, fivefold),
      without affecting lung growth or increasing inflammatory cells in the lung. Both
      genders, and upper and lower lung lobes were similarly affected. IL-1ra did not
      modify SP-A, -B, or -C mRNA. IL-1 increased the intensity of staining of alveolar
      type II cells for SP-B, and the concentrations of SP-B, -A, and disaturated
      phosphatidylcholine in bronchoalveolar lavage. The dynamic lung compliance and
      the postventilatory expansion of lungs were increased two- to fourfold after IL
      1alpha treatment. In fetal lung explants, IL-1alpha increased the expression of
      SP-A mRNA. IL-1 in amniotic fluid in preterm labor may promote lung maturation
      and thus be part of a host-defense mechanism that prepares the fetus for
      extrauterine life.

PMID- 9185522
TI  - Differential screening of a human chromosome 3 library identifies hepatocyte
      growth factor-like/macrophage-stimulating protein and its receptor in injured
      lung. Possible implications for neuroendocrine cell survival.
AB  - Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung
      tumors develop in nitrosaminetreated hamsters, which we hypothesized might
      modulate epithelial cell phenotype by expressing gene(s) homologous to human
      chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We
      differentially screened a chromosome 3 library using nitrosamine-treated versus
      normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage
      stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to
      undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase
      receptor, RON, is present and functional on many of these neuroendocrine tumors.
      In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/ MSP
      induced adhesion/flattening and apoptosis. Using viable cell counts to assess
      proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition
      of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary
      neuroendocrine cell apoptosis in situ during the same time period as expression
      of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous
      regression of neuroendocrine cell hyperplasia. These observations suggest that
      HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung
      injury, which could influence the ultimate tumor cell phenotype.

PMID- 9185524
TI  - Deoxyribonucleic acid triplex formation inhibits granulocyte macrophage colony
      stimulating factor gene expression and suppresses growth in juvenile
      myelomonocytic leukemic cells.
AB  - Juvenile myelomonocytic leukemia (JMML) is a severe childhood malignancy. The
      autocrine production of GMCSF is believed to be responsible for the spontaneous
      proliferation of JMML cells. A nuclear factor-kappaB (NF-kappaB)/Rel binding site
      within the GM-CSF gene promoter, termed the kappaB element, plays an important
      role in controlling transcription from the GM-CSF gene. We investigated the
      effect of an oligonucleotide GM3, directed to form a DNA triple helix across this
      kappaB element, on growth and GM-CSF production by JMML cells. Treatment of these
      cells, either unstimulated or induced by TNFalpha, with GM3 led to a significant
      and specific inhibition of both GM-CSF production and spontaneous colony
      formation. This constitutes the first report linking specific triplex-mediated
      inhibition of gene transcription with a functional outcome; i.e., cell growth. We
      observed the constitutive presence of NF-kappaB/Rel proteins in the nucleus of
      JMML cells. The constitutive and TNFalpha-induced NF-kappaB/Rel complexes were
      identical and were composed mainly of p50 and c-Rel proteins. Treatment of the
      cells with a neutralizing anti-TNFalpha monoclonal antibody completely abrogated
      constitutive nuclear expression of NF-kappaB/Rel proteins. These results indicate
      that the aberrant, constitutive GM-CSF gene activation in JMML is maintained by
      TNFalpha-mediated activation of NF-kappaB/Rel proteins. Our findings identify the
      molecular basis for the autocrine TNFalpha activation of the GM-CSF gene in JMML
      and suggest potential novel and specific approaches for the treatment of this
      aggressive childhood leukemia.

PMID- 9185525
TI  - Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes
      in atopic dermatitis. Implications for sustained dendritic cell activation in the
      skin.
AB  - Lesional skin of atopic dermatitis (AD) harbors high numbers of dendritic cells
      with enhanced stimulatory capacity for T lymphocytes. In this study, lesional AD
      skin was shown to stain heavily in both epidermal and dermal compartments for GM
      CSF, a cytokine crucial to dendritic cell functions. Keratinocyte cultures
      established from uninvolved skin of AD patients exhibited markedly increased
      spontaneous and PMA-stimulated release of GM-CSF compared with keratinocytes from
      nonatopic controls. Correspondingly, keratinocytes from AD patients showed higher
      constitutive as well as PMA-induced GM-CSF gene expression. Larger amounts of GM
      CSF were produced by AD keratinocytes, also in response to IL-1alpha, but not
      after stimulation with LPS, lipoteichoic acid, or staphylococcal enterotoxin B.
      Hydrocortisone reduced GM-CSF gene expression and protein release in both atopic
      and control keratinocytes. Supernatants from atopic keratinocytes were able to
      strongly stimulate PBMC proliferation in a GM-CSF-dependent manner. Moreover,
      conditioned medium from PMA-treated AD keratinocytes, together with exogenous IL
      4, could support phenotypical and functional maturation of peripheral blood
      precursors into dendritic cells. Enhanced production of GM-CSF by keratinocytes
      may contribute relevantly to the establishment and chronicity of AD lesions, in
      particular to the increased number, sustained activation, and enhanced antigen
      presenting functions of dendritic cells.

PMID- 9185526
TI  - Familial congenital hypothyroidism due to inactivating mutation of the
      thyrotropin receptor causing profound hypoplasia of the thyroid gland.
AB  - Thyroid gland agenesis is the most common cause of congenital hypothyroidism and
      is usually sporadic. We investigated a brother and sister from consanguineous
      parents, ascertained through systematic newborn screening, and initially
      diagnosed with thyroid agenesis. Careful cervical ultrasonography in both
      patients revealed a very hypoplastic thyroid gland. By direct sequencing of the
      thyrotropin receptor gene, we identified the substitution of threonine in place
      of a highly conserved alanine at position 553, in the fourth predicted
      transmembrane domain. The mutation was found homozygous in the affected siblings,
      and heterozygous in both parents and two unaffected siblings. Functional analysis
      in transfected COS-7 cells showed that it resulted in extremely low expression at
      the cell surface as compared with the wild-type receptor, in spite of an
      apparently normal intracellular synthesis. The small amount of mutated receptor
      expressed at the surface of transfected cells bound thyrotropin with normal
      affinity and responded in terms of cAMP production, but the in vivo significance
      of these data from overexpressed receptor in transfected cells is unclear. Of
      note, blood thyroglobulin was unexpectedly elevated in the patients at the time
      of diagnosis, a finding that might prove useful in refining etiologies of
      congenital hypothyroidism.

PMID- 9185527
TI  - Interleukin-12 induction of Th1 cytokines is important for viral clearance in
      chronic hepatitis B.
AB  - Interleukin-12, a cytokine with an important role against intracellular
      pathogens, promotes Th1 cell development, cellmediated cytotoxicity, and
      interferon-gamma production. We investigated the immunoregulatory role of IL-12
      in 72 chronic hepatitis B virus (HBV) carriers, 33 of whom were monitored
      longitudinally during interferon-alpha treatment. Serum levels of IL-12
      heterodimer, IL-12 p40 subunit, IL-4, and Th1 cytokines were determined by
      specific ELISAs, and hepatitis B core antigen-specific T cell response by a
      proliferation assay. Chronic HBV carriers had higher serum levels of IL-12 and IL
      12 p40 in comparison with controls (P < 0.01), suggesting that IL-12 production
      is not impaired. The longitudinal analysis revealed a further substantial
      increase (> 2.5x baseline level) of bioactive IL-12 and Th1 cytokines in patients
      who cleared HBV and seroconverted to anti- hepatitis B e, unlike the 23
      nonresponders with persistent HBV replication (P < 0.01). The IL-12 peak followed
      the peak of hepatocytolysis by 9.8+/-2.8 wk and occurred either before or
      simultaneously with hepatitis B e seroconversion. Hepatitis B core antigen
      specific T cell proliferation closely correlated with hepatocytolysis and
      increased significantly in all patients (8 responders and 15 nonresponders) who
      developed hepatitis flare, irrespective of the virological outcome. These results
      provide in vivo evidence that IL-12 may have an important role for viral
      clearance in chronic HBV infection.

PMID- 9185528
TI  - A common mutation (G-455--> A) in the beta-fibrinogen promoter is an independent
      predictor of plasma fibrinogen, but not of ischemic heart disease. A study of
      9,127 individuals based on the Copenhagen City Heart Study.
AB  - A common mutation (G-455--> A) in the promoter region of the beta-fibrinogen gene
      has been associated with elevated plasma fibrinogen levels. Whether fibrinogen
      genotype affects plasma fibrinogen levels and risk of ischemic heart disease in
      the general population has not been studied. We investigated the association
      between fibrinogen genotype, plasma fibrinogen levels, and ischemic heart disease
      in a general population sample (n = 9,127). The A-allele (relative frequency,
      0.20) was associated with elevated plasma fibrinogen levels in both genders (P <
      0.001). While the effect of the A-allele on fibrinogen level was additive in men,
      the effect was dominant in postmenopausal women. The A-allele raising effect
      appeared to be two- to threefold greater in individuals with ischemic heart
      disease than in those without. An increase of 1 SD in plasma fibrinogen increased
      the odds ratio for ischemic heart disease by approximately 20% (P < 0.01 for
      women and < 0.005 for men). However, the frequency of the A-allele was similar in
      those with and without ischemic heart disease, and genotype was not a predictor
      of disease. These results demonstrate that the (G-455--> A) mutation in the
      promoter region of the beta-fibrinogen gene is associated with an increase in
      plasma fibrinogen in both genders in the general population. This increase does
      not appear to cause ischemic heart disease.

PMID- 9185529
TI  - An NF-kappaB-like transcription factor in axoplasm is rapidly inactivated after
      nerve injury in Aplysia.
AB  - We found a protein in Aplysia neurons that has many characteristics of the
      transcription factor NF-kappaB. Thus, the protein recognized a radiolabeled probe
      containing the kappaB sequence from the human interferon-beta gene enhancer
      element (PRDII), and the binding was not affected by PRDIV, an ATF-2 enhancer
      sequence from the same gene. Binding was efficiently inhibited, however, by
      nonradioactive oligonucleotides containing H2, the kappaB site from the major
      histocompatibility complex I gene promotor. In addition, recombinant mammalian
      IkappaB-alpha, which associates specifically with the P65 subunit of NF-kappaB,
      inhibited the binding to the PRDII probe in a dose-dependent manner. The nuclear
      form of the Aplysia protein was constitutively active. Axoplasm, however,
      contained the constitutively active form as well as a latent form. The latter was
      activated by treatment with deoxycholate under the same conditions as mammalian
      NF-kappaB. Based on these findings, we believe the protein to be a homolog of NF
      kappaB. To investigate the role of apNF-kappaB in the axon, we crushed the
      peripheral nerves to the body wall. Surprisingly, there was a rapid loss of apNF
      kappaB binding at the crush site and, within 15 min, as far as 2.5 cm along the
      axon. In contrast, exposing either the intact animal or the nervous system in
      situ to levels of 5-HT that induce synaptic facilitation did not affect apNF
      kappaB activity.

PMID- 9185530
TI  - Microtubule organization and stability in the oligodendrocyte.
AB  - The oligodendrocyte is the glial cell responsible for the formation and
      maintenance of CNS myelin. Because the development of neuronal morphology is
      known to depend on the presence of highly organized microtubule arrays, it may be
      hypothesized that the properties of microtubules influence the form and function
      of oligodendrocytes. The goals of the present study were to define the physical
      attributes of microtubules in oligodendrocytes maintained in vitro. The results
      of electron and confocal microscopy indicate that microtubules are present
      throughout the cell bodies and large and small processes of oligodendrocytes and
      are rarely associated with discrete microtubule-organizing centers. A modified
      "hooking" protocol demonstrated that the polarity orientation of microtubules is
      uniformly plus-end distal in small oligodendrocyte processes, compared with a
      nonuniform, predominantly plus-end distal orientation in large processes.
      Oligodendrocytes were exposed to the microtubule-depolymerizing drug nocodazole
      to examine microtubule stability in these cells. The results suggest that
      oligodendrocyte microtubules can be resolved into at least three distinct
      microtubule populations that differ in their kinetics of depolymerization in the
      presence of nocodazole. These findings suggest that the properties of the
      oligodendrocyte microtubule array reflect the functions of the different regions
      of this highly specialized cell.

PMID- 9185531
TI  - Chronic Fos-related antigens: stable variants of deltaFosB induced in brain by
      chronic treatments.
AB  - Fos family transcription factors are believed to play an important role in the
      transcriptional responses of the brain to a variety of stimuli. Previous studies
      have described 35 and 37 kDa Fos-like proteins, termed chronic Fos-related
      antigens (FRAs), that are induced in brain in a region-specific manner in
      response to several chronic perturbations, including chronic electroconvulsive
      seizures, psychotropic drug treatments, and lesions. We show in this study that
      the chronic FRAs are isoforms of deltaFosB, a truncated splice variant of FosB
      that accumulate in brain after chronic treatments because of their stability.
      doffaFosB cDNA encodes the expression of 33, 35, and 37 kDa proteins that arise
      from a single AUG translation start site. The 35 and 37 kDa proteins correspond
      to the chronic FRAs that are induced in brain by chronic treatments, whereas the
      33 kDa protein corresponds to a Fos-like protein that is induced in brain by
      acute treatments, findings based on migration on one- and two-dimensional Western
      blots with anti-FRA and anti-FosB antibodies. Using cells in which deltaFosB or
      FosB expression is under the control of a tetracycline-regulated gene expression
      system, we show that the 37 kDa deltaFosB protein exhibits a remarkably long half
      life, the 35 kDa DeltaFosB protein exhibits an intermediate half-life, and the 33
      kDa deltaFosB protein and all FosB-derived proteins exhibit relatively short half
      lives. Moreover, we show that the 33 kDa deltaFosB protein is the first to appear
      after activation of deltaFosB expression. Finally, deltaFosB proteins are shown
      to possess DNA-binding activity and to exert potent transactivating effects in
      reporter gene assays. Together, these findings support a scheme wherein
      deltaFosB, expressed as a 33 kDa protein, is modified to form highly stable
      isoforms of 35 and 37 kDa. As a result, these stable isoforms gradually
      accumulate in the brain with repeated treatments to mediate forms of long-lasting
      neural and behavioral plasticity.

PMID- 9185532
TI  - Redox modulation of hslo Ca2+-activated K+ channels.
AB  - The modulation of ion channel proteins by cellular redox potential has emerged
      recently as a significant determinant of channel function. We have investigated
      the influence of sulfhydryl redox reagents on human brain Ca2+-activated K+
      channels (hslo) expressed in both human embryonic kidney 293 cells and Xenopus
      oocytes using macropatch and single-channel analysis. Intracellular application
      of the reducing agent dithiothreitol (DTT): (1) shifts the voltage of half
      maximal channel activation (V0.5) approximately 18 mV to more negative potentials
      without affecting the maximal conductance or the slope of the voltage dependence;
      (2) slows by approximately 10-fold a time-dependent right-shift in V0.5 values
      ("run-down"); (3) speeds macroscopic current activation kinetics by approximately
      33%; and (4) increases the single-channel open probability without affecting the
      unitary conductance. In contrast to DTT treatment, oxidation with hydrogen
      peroxide shifts macropatch V0.5 values to more positive potentials, increases the
      rate of channel run-down, and decreases the single-channel open probability. KCa
      channels cloned from Drosophila differ from hslo channels in that they show very
      little run-down and are not modulated by the addition of DTT. These data indicate
      that hslo Ca2+-activated K+ channels may be modulated by changes in the cellular
      redox potential as well as by the transmembrane voltage and the cytoplasmic Ca2+
      concentration.

PMID- 9185533
TI  - Adenosine A1 receptor-mediated activation of phospholipase C in cultured
      astrocytes depends on the level of receptor expression.
AB  - Adenosine A1 receptors induce an inhibition of adenylyl cyclase via G-proteins of
      the Gi/o family. In addition, simultaneous stimulation of A1 receptors and of
      receptor-mediated activation of phospholipase C (PLC) results in a synergistic
      potentiation of PLC activity. Evidence has accumulated that Gbetagamma subunits
      mediate this potentiating effect. However, an A1 receptor-mediated increase in
      extracellular glutamate was suggested to be responsible for the potentiating
      effect in mouse astrocyte cultures. We have investigated the synergistic
      activation of PLC by adenosine A1 and alpha1 adrenergic receptors in primary
      cultures of astrocytes derived from different regions of the newborn rat brain.
      It is reported here that (1) adenosine A1 receptor mRNA as well as receptor
      protein is present in astrocytes from all brain regions, (2) A1 receptor-mediated
      inhibition of adenylyl cyclase is of similar extent in all astrocyte cultures,
      (3) the A1 receptor-mediated potentiation of PLC activity requires higher
      concentrations of agonist than adenylyl cyclase inhibition and is dependent on
      the expression level of A1 receptor, and (4) the potentiating effect on PLC
      activity is unrelated to extracellular glutamate. Taken together, our data
      support the notion that betagamma subunits are the relevant signal transducers
      for A1 receptor-mediated PLC activation in rat astrocytes. Because of the lower
      affinity of betagamma, as compared with alpha subunits, more betagamma subunits
      are required for PLC activation. Therefore, only in cultures with higher levels
      of adenosine A1 receptors is the release of betagamma subunits via Gi/o
      activation sufficient to stimulate PLC. It is concluded that variation of the
      expression level of adenosine A1 receptors may be an important regulatory
      mechanism to control PLC activation via this receptor.

PMID- 9185534
TI  - Motor pattern selection via inhibition of parallel pathways.
AB  - Motor pattern selection from a multifunctional neural network often results from
      direct synaptic and modulatory actions of different projection neurons onto
      neural network components. Less well documented is the presence and function of
      interactions among distinct projection neurons innervating the same network. In
      the stomatogastric nervous system of the crab Cancer borealis, several distinct
      projection neurons that influence the pyloric and gastric mill rhythms have been
      studied. These rhythms are generated by overlapping subsets of identified neurons
      in the stomatogastric ganglion (STG). One of these identified projection neurons
      is the modulatory proctolin neuron (MPN). We showed previously that MPN
      stimulation excites the pyloric rhythm by its excitatory actions on STG neurons.
      In contrast to its excitatory actions on the pyloric rhythm, we have now found
      that MPN inhibits the gastric mill rhythm. This inhibition does not occur within
      the STG, but instead results from MPN-mediated inhibition of two previously
      identified projection neurons within the commissural ganglia. These projection
      neurons innervate the STG and, via their actions on STG neurons, they elicit the
      gastric mill rhythm as well as modify the pyloric rhythm in a manner distinct
      from MPN. By inhibiting these projection neurons, MPN removes excitatory drive to
      gastric mill neurons and elicits an MPN-specific pyloric rhythm. Motor pattern
      selection by MPN therefore results from both a direct modulation of STG network
      activity and an inhibition of competing pathways.

PMID- 9185535
TI  - Site-specific and sensory neuron-dependent increases in postsynaptic glutamate
      sensitivity accompany serotonin-induced long-term facilitation at Aplysia
      sensorimotor synapses.
AB  - Long-term changes in the efficacy of Aplysia sensory neuron (SN) connections
      accompany behavioral training or applications with 5-HT. The changes evoked by
      training or 5-HT include formation of new SN varicosities and transmitter release
      sites. Because new synapse formation requires proper alignment of presynaptic
      structures with postsynaptic zones containing a high density of transmitter
      receptors, we examined whether changes in postsynaptic sensitivity to the
      presumed SN transmitter (glutamate) were correlated with formation and
      distribution of new SN varicosities in contact with motor cell L7 in cell
      culture. The formation of stable SN connections after 4 d in culture did not
      significantly change overall responses to focal applications of glutamate.
      However, specific sites along L7's axon apposed to SN varicosities expressed
      larger responses to glutamate compared with adjacent sites with few SN
      varicosities. After treatments with 5-HT that evoked long-term changes in both
      the structure and the function of SN-L7 synaptic interaction, glutamate responses
      increased selectively at sites along the surface of L7's axon with preexisting or
      new SN varicosities. Increases in postsynaptic response to glutamate 24 hr after
      5-HT treatment required interaction with an SN. These results suggest that new
      synapse formation between neurons, either with regeneration or after external
      stimuli that evoke increases in synaptic efficacy, involves site-specific changes
      in expression of functional neurotransmitter receptors on the postsynaptic cell
      that is regulated by interaction with the presynaptic neuron.

PMID- 9185536
TI  - Appican expression induces morphological changes in C6 glioma cells and promotes
      adhesion of neural cells to the extracellular matrix.
AB  - Appicans are secreted or cell-associated brain chondroitin sulfate proteoglycans
      produced by glia cells and containing Alzheimer amyloid precursor protein (APP)
      as a core protein. Here, we report that rat C6 glioma cells transfected with
      appican displayed a dramatic change in their phenotypic appearance compared with
      untransfected cells or cells transfected with APP. Appican-transfected cells lost
      the round appearance of the untransfected control C6 cells, acquired a flat
      morphology, and elaborated more processes than control cells. Untransfected, or
      APP-transfected C6, cells were completely dissociated from their substrate after
      40 min of treatment with cell dissociation solution. Under the same conditions,
      however, <20% of the appican-transfected C6 cells were dissociated from their
      substrate, suggesting that the appican-transfected glia cells attach more avidly
      to their substrate than do untransfected or APP transfected control cells. In
      contrast, appican-transfected fibroblast cells showed no morphological changes
      and dissociated from their substrate similarly to untransfected fibroblast cells.
      Extracellular matrix (ECM) prepared from appican-transfected C6 cell cultures
      contained high levels of appican and was a significantly better substrate for the
      attachment of C6 cells than ECM from either untransfected or APP-transfected
      cultures. Furthermore, cell adhesion to ECM was independent of the level of
      appican expression of the plated cells. ECM from appican-transfected C6 cultures
      stimulated adhesion of other neural cells including primary astrocytes, Neuro2a
      neuroblastoma, and PC12 pheochromocytoma, but not fibroblast cells. Conditioned
      media from appican-transfected C6 cultures failed to promote cell adhesion.
      Together, these data suggest that secreted appican incorporates into ECM and
      promotes adhesion of neural cells. Furthermore, our data suggest that the
      chondroitin sulfate chain engenders APP with novel biological functions.

PMID- 9185537
TI  - Cholecystokinin increases GABA release by inhibiting a resting K+ conductance in
      hippocampal interneurons.
AB  - Cholecystokinin (CCK) is found co-localized with the inhibitory neurotransmitter
      GABA in interneurons of the hippocampus. Also, CCK receptors are found in
      abundance in this brain region. The possibility that CCK alters interneuron
      activity was examined using whole-cell current- and voltage-clamp recordings from
      visualized interneurons in the stratum radiatum of area CA1 in rat hippocampal
      slices. The effect of CCK on GABA-mediated IPSCs was also determined in pyramidal
      neurons. The sulfated octapeptide CCK-8S increased action potential frequency or
      generated inward currents in the majority of interneurons. These effects of CCK
      persisted in the presence of tetrodotoxin and cadmium, suggesting that they were
      direct. Current-voltage plots revealed that CCK-8S inhibited a conductance that
      was linear across command potentials and reversed near the equilibrium potential
      for K+ ions. The K+ channel blocker tetraethylammonium (10 mM) generated inward
      currents similar to those initiated by CCK, and it occluded the effect of the
      peptide. BaCl2 (1 mM) and 4-aminopyridine (2 mM) did not alter the effect of CCK.
      The CCKB receptor antagonist PD-135,158 completely blocked the inward currents
      generated by CCK-8S. CCK also resulted in an increase in spontaneous action
      potential-dependent IPSC frequency, but no changes in action potential
      independent miniature IPSCs or evoked IPSCs in pyramidal neurons. These results
      provide evidence that CCK can depolarize hippocampal interneurons through the
      inhibition of a resting K+ conductance, leading to increased tonic inhibition of
      pyramidal neurons. This action of CCK may contribute to its anticonvulsant
      properties, as observed in limbic seizure models.

PMID- 9185538
TI  - Stretch hyperreflexia of triceps surae muscles in the conscious cat after
      dorsolateral spinal lesions.
AB  - Resistive force and electromyograms from triceps surae muscles were measured
      during dorsiflexion of both ankles of awake cats before and after interruption of
      one dorsolateral funiculus (DLF). DLF lesions produced ipsilateral increases in
      dynamic and static reflex force that persisted over 66 weeks. The increase in
      dynamic reflex force was velocity sensitive, as demonstrated by a greater effect
      for 60 degrees /sec than for 10 degrees /sec dorsiflexion. Also, the lesions
      increased dynamic force to a greater extent than static force (increased dynamic
      index). Background force (recorded immediately before each reflex response) was
      elevated ipsilaterally. However, increases in reflex force were observed when
      preoperative and postoperative background forces were matched within 10% and were
      associated with equivalent resting levels of electromyographic (EMG) activity.
      Resistive reflex force was significantly correlated with EMG responses to
      dorsiflexion and was not determined by nonreflexive mechanical stiffness of the
      muscles. Contralateral background and reflex force and associated EMG activity
      were decreased slightly, comparing preoperative and postoperative records.
      Clinical testing revealed ipsilateral postoperative increases in extensor tone,
      increased resistance to hindlimb flexion, hypermetria during positive support
      responses, and appearance of the Babinski reflex. However, the most reliable
      tests of DLF lesion effects were the quantitative measures of dynamic and static
      reflex amplitude. The enhancement of stretch reflexes is suggestive of
      spasticity. However, hyperactive stretch reflexes, hypertonicity, and the
      Babinski reflex were observed soon after interruption of the ipsilateral DLF, in
      contrast to a gradual development of positive signs that is characteristic of a
      more broadly defined spastic syndrome from large spinal lesions. Also, other
      signs that often are included in the spastic syndrome, including clonus,
      increased flexor reflex activity, and flexor spasms, did not result from DLF
      lesions. Thus, unilateral DLF lesions provide a model of spasticity but produce
      only several components of a more inclusive spastic syndrome.

PMID- 9185539
TI  - Chick ciliary ganglion neurons contain transcripts coding for acetylcholine
      receptor-associated protein at synapses (rapsyn).
AB  - A peripheral membrane protein of approximately 43 kDa (rapsyn) clusters muscle
      nicotinic acetylcholine receptors (AChRs), but molecules relevant to clustering
      neuronal AChRs have not been identified. Here, we have detected rapsyn
      transcripts in the chick nervous system, localized rapsyn mRNA in ciliary
      ganglion (CG) neurons, which are known to cluster AChRs, and identified three
      rapsyn cDNAs derived from the ganglion. Our initial Northern blots, performed
      using a mouse probe, revealed rapsyn-like transcripts in chick muscle and brain.
      To develop species-specific probes, we prepared a chick rapsyn cDNA construct,
      Ch43K.1, that encodes a protein having extensive homology to mouse rapsyn. Using
      primers designed to anneal near the 5' and 3' boundaries of Ch43K.1, three
      prominent cDNAs were amplified from chick muscle templates by reverse
      transcriptase based-PCR. Products of similar size were also amplified using cDNA
      prepared from neuronal tissues expected to contain clustered AChRs (CG and
      brain), whereas none were detected using templates from tissues not displaying
      clustered AChRs (sensory ganglia and liver). In situ hybridization confirmed that
      rapsyn mRNA is expressed both in chick muscle fibers and in CG neurons.
      Sequencing the three cDNAs amplified from CG templates revealed the largest to be
      Ch43K.1, whereas the smaller two may represent splice variants. These findings
      suggest that multiple rapsyn-like molecules are involved in clustering the
      distinct AChRs expressed by muscle fibers and neurons.

PMID- 9185540
TI  - Neuronally restricted RNA splicing regulates the expression of a novel GABAA
      receptor subunit conferring atypical functional properties [corrected; erratum to
      be published].
AB  - We report the isolation and characterization of a cDNA encoding a novel member of
      the GABA receptor gene family, epsilon. This polypeptide is 506 amino acids in
      length and exhibits its greatest amino acid sequence identity with the GABAA
      receptor gamma3 subunit (47%), although this degree of homology is not sufficient
      for it to be classified as a fourth gamma subunit. The epsilon subunit
      coassembles with GABAA receptor alpha and beta subunits in Xenopus laevis oocytes
      and transfected mammalian cells to form functional GABA-gated channels.
      alpha1beta1epsilon GABAA receptors, like alpha1beta1gamma2s receptors, are
      modulated by pentobarbital and the steroid 5alpha-pregnan-3alpha-ol-20-one but,
      unlike alpha1beta1gamma2s receptors, are insensitive to flunitrazepam.
      Additionally, alpha1beta1epsilon receptors exhibit rapid desensitization
      kinetics, as compared with alpha1beta1 or alpha1beta1gamma2s. Northern analysis
      demonstrates widespread expression of a large epsilon subunit transcript in a
      variety of non-neuronal tissues and expression of a smaller transcript in brain
      and spinal cord. Sequence analysis demonstrated that the large transcript
      contained an unspliced intron, whereas the small transcript represents the mature
      mRNA, suggesting regulation of expression of the epsilon subunit via neuronally
      restricted RNA splicing. In situ hybridization and immunocytochemistry reveal a
      pattern of expression in the brain restricted primarily to the hypothalamus,
      suggesting a role in neuroendocrine regulation, and also to subfields of the
      hippocampus, suggesting a role in the modulation of long term potentiation and
      memory.

PMID- 9185541
TI  - Tyrosine phosphorylation of nicotinic acetylcholine receptor mediates Grb2
      binding.
AB  - Tyrosine phosphorylation of the nicotinic acetylcholine receptor (AChR) is
      associated with an altered rate of receptor desensitization and also may play a
      role in agrin-induced receptor clustering. We have demonstrated a previously
      unsuspected interaction between Torpedo AChR and the adaptor protein Grb2. The
      binding is mediated by the Src homology 2 (SH2) domain of Grb2 and the tyrosine
      phosphorylated delta subunit of the AChR. Dephosphorylation of the delta subunit
      abolishes Grb2 binding. A cytoplasmic domain of the delta subunit contains a
      binding motif (pYXNX) for the SH2 domain of Grb2. Indeed, a phosphopeptide
      corresponding to this region of the delta subunit binds to Grb2 SH2 fusion
      proteins with relatively high affinity, whereas a peptide lacking phosphorylation
      on tyrosine exhibits no binding. Grb2 is colocalized with the AChR on the
      innervated face of Torpedo electrocytes. Furthermore, Grb2 specifically
      copurifies with AChR solubilized from postsynaptic membranes. These data suggest
      a novel role for tyrosine phosphorylation of the AChR in the initiation of a Grb2
      mediated signaling cascade at the postsynaptic membrane.

PMID- 9185542
TI  - Cellular composition and three-dimensional organization of the subventricular
      germinal zone in the adult mammalian brain.
AB  - The adult mammalian subventricular zone (SVZ) contains stem cells that give rise
      to neurons and glia. In vivo, SVZ progeny migrate 3-8 mm to the olfactory bulb,
      where they form neurons. We show here that the SVZ of the lateral wall of the
      lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a
      novel putative precursor cell. The topographical organization of these cells
      suggests how neurogenesis and migration are integrated in this region. Type A
      cells had the ultrastructure of migrating neuronal precursors. These cells were
      arranged as chains parallel to the walls of the ventricle and were polysialylated
      neural adhesion cell molecule- (PSA-NCAM), TuJ1- (beta-tubulin), and nestin
      positive but GFAP- and vimentin-negative. Chains of Type A cells were ensheathed
      by two ultrastructurally distinct astrocytes (Type B1 and B2) that were GFAP-,
      vimentin-, and nestin-positive but PSA-NCAM- and TuJ1-negative. Type A and B2
      (but not B1) cells incorporated [3H]thymidine. The most actively dividing cell in
      the SVZ corresponded to Type C cells, which had immature ultrastructural
      characteristics and were nestin-positive but negative to the other markers. Type
      C cells formed focal clusters closely associated with chains of Type A cells.
      Whereas Type C cells were present throughout the SVZ, they were not found in the
      rostral migratory stream that links the SVZ with the olfactory bulb. These
      results suggest that chains of migrating neuroblasts in the SVZ may be derived
      from Type C cells. Our results provide a topographical model for the adult SVZ
      and should serve as a basis for the in vivo identification of stem cells in the
      adult mammalian brain.

PMID- 9185543
TI  - Modulation of GABAA receptor function by tyrosine phosphorylation of beta
      subunits.
AB  - Protein tyrosine phosphorylation is a key event in diverse intracellular
      signaling pathways and has been implicated in modification of neuronal
      functioning. We investigated the role of tyrosine phosphorylation in regulating
      type A GABA (GABAA) receptors in cultured CNS neurons. Extracellular application
      of genistein (50 microM), a membrane-permeable inhibitor of protein tyrosine
      kinases (PTKs), produced a reversible reduction in the amplitude of GABAA
      receptor-mediated whole-cell currents, and this effect was not reproduced by
      daidzein (50 microM), an inactive analog of genistein. In contrast, intracellular
      application of the PTK pp60(c-src) (30 U/ml) resulted in a progressive increase
      in current amplitude, and this potentiation was prevented by pretreatment of the
      neurons with genistein. Immunoprecipitation and immunoblotting of cultured
      neuronal homogenates indicated that the beta2/beta3 subunit(s) of the GABAA
      receptor are tyrosine phosphorylated in situ. Moreover, genistein (50 microM) was
      found to be capable of decreasing GABAA currents in human embryonic kidney 293
      cells transiently expressing functional GABAA receptors containing the beta2
      subunit. Thus, the present work provides the first evidence that native GABAA
      receptors are phosphorylated and modulated in situ by endogenous PTKs in cultured
      CNS neurons and that phosphorylation of the beta subunits may be sufficient to
      support such a modulation. Given the prominent role of GABAA receptors in
      mediating many brain functions and dysfunctions, modulation of these receptors by
      PTKs may be important in a wide range of physiological and pathological processes
      in the CNS.

PMID- 9185544
TI  - A family of delayed rectifier Kv1 cDNAs showing cell type-specific expression in
      the squid stellate ganglion/giant fiber lobe complex.
AB  - Squid giant axons are formed by giant fiber lobe (GFL) neurons of the stellate
      ganglion (SG). Other large motoneurons in the SG form a parallel system. A small
      family of cDNAs (SqKv1A-D) encoding Kv1 alpha-subunits was identified in a squid
      (Loligo opalescens) SG/GFL library. Members have distinct 5' untranslated regions
      (UTRs) and initial coding regions, but beyond a certain point (nucleotide 34 of
      SqKv1A) only nine differences exist. 3' UTRs are identical. Predicted alpha
      subunits are nearly identical, and only the N termini differ significantly,
      primarily in length. RNase protection assays that use RNA isolated from specific
      SG regions show that SqKv1A mRNA is expressed prominently in the GFL but not in
      the SG proper. SqKv1B yields the opposite pattern. SqKv1D also is expressed only
      in the SG. SqKv1C expression was not detectable. In situ hybridizations confirm
      these results and reveal that SqKv1B mRNA is abundant in many large neurons of
      the SG, whereas SqKv1D expression is limited to small isolated clusters of
      neurons. SqKv1A and B are thus the predominant Kv1 mRNAs in the SG/GFL complex.
      Activation properties of SqKv1A and B channels expressed in oocytes are very
      similar to one another and compare favorably with properties of native delayed
      rectifier channels in GFL neurons and large SG neurons. The Kv1 complement in
      these squid neurons thus seems to be relatively simple. Several differences exist
      between cloned and native channels, however, and may reflect differences in the
      cellular environments of oocytes and neurons.

PMID- 9185545
TI  - Clustering of voltage-sensitive sodium channels on axons is independent of direct
      Schwann cell contact in the dystrophic mouse.
AB  - The distribution of voltage-sensitive sodium channels on axons in the dorsal and
      ventral spinal roots of the dystrophic mouse 129/ReJ-Lama2dy was determined via
      immunocytochemistry. In these nerves there are regions in which Schwann cells
      fail to proliferate and myelinate axons in a normal manner, leaving bundles of
      closely packed large-diameter amyelinated axons. We have identified discrete and
      focal concentrations of sodium channel immunoreactivity on these axons by both
      confocal immunofluorescence and immunoelectron microscopy, using a peptide
      derived polyclonal antibody. In addition, simultaneous labeling with an antibody
      recognizing neuronal-specific ankyrinG revealed a distinct colocalization with
      the sodium channels on both normal and amyelinated axons. The presence of patches
      of sodium channels along with their anchoring protein on amyelinated axons in the
      absence of intervening Schwann cells demonstrates that axons can form and
      maintain independently these initial aggregations. This confirms that direct
      contact between Schwann cell and axon is not required for the formation of sodium
      channel patches of nodal dimensions and density. Furthermore, this strongly
      suggests that local transfer of sodium channels from Schwann cells to axons is
      not required for this process.

PMID- 9185546
TI  - Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal
      apoptosis.
AB  - Oxidative stress is believed to play important roles in neuronal cell death
      associated with many different neurodegenerative conditions (e.g., Alzheimer's
      disease, Parkinson's disease, and cerebral ischemia), and it is believed also
      that apoptosis is an important mode of cell death in these disorders. Membrane
      lipid peroxidation has been documented in the brain regions affected in these
      disorders as well as in cell culture and in vivo models. We now provide evidence
      that 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation,
      is a key mediator of neuronal apoptosis induced by oxidative stress. HNE induced
      apoptosis in PC12 cells and primary rat hippocampal neurons. Oxidative insults
      (FeSO4 and amyloid beta-peptide) induced lipid peroxidation, cellular
      accumulation of HNE, and apoptosis. Bcl-2 prevented apoptosis of PC12 cells
      induced by oxidative stress and HNE. Antioxidants that suppress lipid
      peroxidation protected against apoptosis induced by oxidative insults, but not
      that induced by HNE. Glutathione, which binds HNE, protected neurons against
      apoptosis induced by oxidative stress and HNE. PC12 cells expressing Bcl-2
      exhibited higher levels of glutathione and lower levels of HNE after oxidative
      stress. Collectively, the data identify that HNE is a novel nonprotein mediator
      of oxidative stress-induced neuronal apoptosis and suggest that the antiapoptotic
      action of glutathione may involve detoxification of HNE.

PMID- 9185547
TI  - Neuronal localization of presenilin-1 and association with amyloid plaques and
      neurofibrillary tangles in Alzheimer's disease.
AB  - Mutations in the presenilin-1 (PS1) gene is a cause of early- onset familial
      Alzheimer's disease (AD). Endogenous PS1 is associated with the endoplasmic
      reticulum in the cell body of undifferentiated SH-SY5Y neuroblastoma cells. At
      early stages of neuronal differentiation in rat hippocampal culture, PS1 appears
      in all neuritic processes and in growth cones. In mature differentiated neurons,
      PS1 is concentrated in the somatodendritic compartment but is also present at
      lower levels in axons. A similar localization of PS1 is observed in vivo in
      neurons of the adult human cerebral cortex. In sporadic AD, PS1 appears in the
      dystrophic neurites of mature amyloid plaques and co-localizes with a subset of
      intraneuronal neurofibrillary tangles (NFTs). About 30% of hippocampal NFTs are
      labeled with a highly specific antibody to the PS1 C-terminal loop domain but not
      with an antibody to the PS1 N terminus. This observation is consistent with a
      potential association of the PS1 C-terminal fragment with NFTs, because PS1 is
      constitutively cleaved to N- and C-terminal fragments in neurons. These results
      suggest that PS1 is highly expressed and broadly distributed during early stages
      of neuronal differentiation, consistent with a role for PS1 in neuronal
      differentiation. Furthermore, the co-localization of PS1 with NFTs and plaque
      dystrophic neurites implicates a role for PS1 in the diverse pathological
      manifestations of AD.

PMID- 9185548
TI  - Diverse expression and distribution of Shaker potassium channels during the
      development of the Drosophila nervous system.
AB  - The spatio-temporal expression of Shaker (Sh) potassium channels (Kch) in the
      developing and adult nervous system of Drosophila has been studied at the
      molecular and histological level using specific antisera. Sh Kch are distributed
      in most regions of the nervous system, but their expression is restricted to only
      certain populations of cells. Sh Kch have been found in the following three
      locations: in synaptic areas of neuropile, in axonal fiber tracks, and in a small
      number of neuronal cell bodies. This wide subcellular localization, together with
      a diverse distribution, implicates Sh Kch in multiple neuronal functions.
      Experiments performed with Sh mutants that specifically eliminate a few of the Sh
      Kch splice variants clearly demonstrate an abundant differential expression and
      usage of the wide repertoire of Sh isoforms, but they do not support the idea of
      extensive segregation of these isoforms among different populations of neurons.
      Sh Kch are predominantly expressed at late stages of postembryonic development
      and adulthood. Strikingly, wide changes in the repertoire of Sh splice isoforms
      occur some time after the architecture of the nervous system is complete,
      indicating that the expression of Sh Kch contributes to the final refinements of
      neuronal differentiation. These late changes in the expression and distribution
      of Sh Kch seem to correlate with activity patterns suggesting that Sh Kch may be
      involved in adaptative mechanisms of excitability.

PMID- 9185549
TI  - Slow kinetics of miniature IPSCs during early postnatal development in granule
      cells of the dentate gyrus.
AB  - Whole-cell patch-clamp recordings were used to investigate the properties of
      GABAA receptor-mediated postsynaptic currents during development in dentate gyrus
      granule cells from neonatal [postnatal day 0 (P0)] to adult rats in brain slices.
      The frequency of miniature IPSCs (mIPSCs) was low at birth and increased
      progressively with age. The mIPSCs of all ages could be satisfactorily fitted
      with the sum of a single exponential rise and single exponential decay. From P0
      to P14, both the rise time and the decay time constants were significantly longer
      than in the adult. The mIPSC rise and decay kinetics did not change during the
      first 2 postnatal weeks, but during the third week the kinetics sped up and by
      P21 attained adult values. In contrast, the amplitude of the mIPSCs did not
      change during development. The synaptic GABAA receptors in immature and adult
      cells showed differential sensitivity to modulators. The subunit-specific
      benzodiazepine agonist zolpidem increased the decay time constant of the IPSCs of
      immature granule cells with a reduced potency compared with the adult.
      Furthermore, zinc decreased the amplitude and decay time constant of mIPSCs from
      developing granule cells, whereas it had no effect on mIPSCs in adult neurons.
      The results reveal for the first time that until the end of the second postnatal
      week the synaptic GABAA receptor-mediated currents in dentate granule cells
      display slower rise and decay kinetics but similar amplitudes compared with
      adult, resulting in a net decrease in synaptic charge transfer during
      development.

PMID- 9185550
TI  - NMDA receptor and the tyrosine phosphorylation of its 2B subunit in taste
      learning in the rat insular cortex.
AB  - We demonstrate that the NMDA receptor is involved in taste learning in the
      insular cortex of the behaving rat and describe two facets of this involvement.
      Blockage of the NMDA receptor in the insular cortex by the reversible antagonist
      APV during training in a conditioned taste aversion (CTA) paradigm impaired CTA
      memory, whereas blockage of the NMDA receptor in an adjacent cortex or before a
      retrieval test had no effect. When rats sampled an unfamiliar taste and hence
      learned about it, either incidentally or in the context of CTA training, the
      tyrosine phosphorylation of the NMDA receptor subunit 2B (NR2B) in the insular
      cortex was specifically increased. The level of tyrosine phosphorylation on NR2B
      was a function of the novelty of the taste stimulus and the quantity of the taste
      substance consumed, properties that also determined the efficacy of the taste
      stimulus as a conditioned stimulus in CTA; however, blockage of the NMDA receptor
      by APV during training did not prevent tyrosine phosphorylation of NR2B. We
      suggest that tyrosine phosphorylation of NR2B subserves encoding of saliency in
      the insular cortex during the first hours after an unfamiliar taste is sampled
      and that this encoding is independent of another, necessary role of NMDA
      receptors in triggering experience-dependent modifications in the insular cortex
      during taste learning. Because a substantial fraction of the NR2B protein in the
      insular cortex seems to be expressed in interneurons, saliency and the tyrosine
      phosphorylation of NR2B correlated with it may modulate inhibition in cortex.

PMID- 9185551
TI  - A role for the right anterior temporal lobe in taste quality recognition.
AB  - We conducted two experiments to examine central processing of the taste of citric
      acid. In the first experiment, elevated citric acid recognition thresholds, but
      normal detection thresholds, were observed in a group of patients who had
      undergone a right anterior temporal lobectomy for the treatment of epilepsy,
      compared with a control group and a group of patients who had undergone the same
      operation in the left hemisphere. In the second study, using positron emission
      tomography, we compared regional cerebral blood flow (rCBF) in a condition in
      which citric acid was presented with one in which water was presented (with
      similar somatosensory stimulation across both conditions). We observed increased
      rCBF bilaterally in the caudolateral orbitofrontal cortex, in the right
      anteromedial temporal lobe, and in the right caudomedial orbitofrontal cortex.
      The elevated recognition thresholds exhibited in patients with resection of the
      right anteromedial temporal lobe may be accounted for by damage in an area
      corresponding to that of the rCBF increase. These results suggest that although
      taste sensation may be computed in the primary taste cortex, recognition requires
      further processing by structures located in the anteromedial temporal lobe.
      Furthermore, they point to preferential processing of this higher-order gustatory
      function by the right cerebral hemisphere.

PMID- 9185552
TI  - Synaptic connections of calretinin-immunoreactive neurons in the human neocortex.
AB  - Previous immunocytochemical studies in the cerebral cortex of various species
      have shown that the calcium-binding protein calretinin (CR) labels specific
      subpopulations of nonspiny nonpyramidal cells (interneurons). The present study
      attempts to characterize morphologically and chemically the microcircuitry of CR
      immunoreactive (CR-ir) neurons in the human temporal neocortex. Postembedding
      immunocytochemistry for CR and GABA and combination immunocytochemistry for CR
      and nonphosphorylated neurofilament protein (NPNFP) or for CR and the calcium
      binding proteins parvalbumin (PV) and calbindin (CB) showed CR multiterminal
      endings frequently innervating the distal apical dendrite or the cell body and
      proximal dendrites of NPNFP-ir or CB-ir pyramidal cells, respectively. Cell
      bodies of interneurons immunoreactive for CB or PV were innervated only
      occasionally by CR multiterminal endings, whereas certain GABA neurons were
      surrounded by them. Furthermore, CR-ir axon terminals formed either symmetrical
      (the majority) or asymmetrical synapses with a variety of postsynaptic elements.
      These results indicate that different subpopulations of CR interneurons exist
      that are specialized for selective innervation of somatic or dendritic regions of
      certain pyramidal and nonpyramidal neurons.

PMID- 9185553
TI  - Brain aging: changes in the nature of information coding by the hippocampus.
AB  - Advanced age in rats is associated with a decline in spatial memory capacities
      dependent on hippocampal processing. As yet, however, little is known about the
      nature of age-related alterations in the information encoded by the hippocampus.
      Young rats and aged rats identified as intact or impaired in spatial learning
      capacity were trained on a radial arm maze task, and then multiple parameters of
      the environmental cues were manipulated to characterize the changes in firing
      patterns of hippocampal neurons corresponding to the presence of particular cues
      or the spatial relationships among them. The scope of information encoded by the
      hippocampus was reduced in memory-impaired aged subjects, even though the number
      of neurons responsive to salient environmental cues was not different from that
      in young rats. Furthermore, after repeated manipulations of the cues, memory
      intact aged rats, like young rats, altered their spatial representations, whereas
      memory-impaired aged rats showed reduced plasticity of their representation
      throughout testing. Thus changes in hippocampal memory representation associated
      with aging and memory loss can be characterized as a rigid encoding of only part
      of the available information.

PMID- 9185554
TI  - Brain aging: impaired coding of novel environmental cues.
AB  - Studies of the spatial memory capacities of aged animals usually focus on
      performance during the learning of new environments. By contrast, efforts to
      characterize age-related alterations in spatial firing information processing by
      hippocampal neurons typically use an environment that is highly familiar to the
      animals. In the present study we compared the firing properties of hippocampal
      neurons in young adult and aged rats as they acquired spatial information about
      new environmental cues. Hippocampal complex spike cells were recorded while rats
      performed a radial arm maze task in a familiar environment and then recorded
      again after many of the spatial cues were changed. After the change in the
      environment, in aged rats 35-42% of place fields retained their original shape
      and location with respect to the maze center, although they usually rotated to
      another arm. By contrast, all place fields in young animals either disappeared or
      appeared in a new location. Some of the new place fields appeared in the new
      environment during the first 5 min of exploration, whereas others needed more
      than 30 min to develop fully. In the familiar environment spatial selectivity of
      place cells was similar in young and aged rats. By contrast, when rats were
      placed into a new environment, spatial selectivity decreased considerably in aged
      memory-impaired rats compared with that of young rats and aged rats with intact
      memory performance.

PMID- 9185555
TI  - Interaction of the hypothalamic paraventricular nucleus and central nucleus of
      the amygdala in naloxone blockade of neuropeptide Y-induced feeding revealed by c
      fos expression.
AB  - Neuropeptide Y (NPY) is a powerful inducer of food intake with a key site of
      action in the paraventricular nucleus (PVN) of the hypothalamus. An effective
      method for inhibiting the effects of NPY is pretreatment with the opioid
      antagonists naloxone or naltrexone. In the present study, we used
      immunohistochemistry for cFos as a marker of neuronal activity to map the effects
      of PVN-injected NPY and blockade of these effects by peripheral injection of
      naloxone. Injection of NPY into the PVN resulted in an increase in food intake
      that was blocked by peripheral administration of naloxone. PVN NPY also resulted
      in increased cFos immunoreactivity (cFos-IR) in the PVN independent of food
      intake, and although peripheral naloxone inhibited NPY-induced feeding, it did
      not alter cFos-IR in the PVN. cFos-IR in the central nucleus of the amygdala
      (CNA) increased in response to both NPY and naloxone. Furthermore, the response
      to NPY and naloxone was additive, suggesting that peripheral naloxone and PVN NPY
      activate different neuronal populations in the CNA. Three other brain regions,
      the nucleus of the solitary tract, the ventrolateral medulla, and the supraoptic
      nucleus, all showed increases in cFos-IR in this study, but these changes came
      only as a result of increased food intake after PVN-injected NPY. The current
      data suggest that the CNA is a site important for the integration of the NPY and
      opioid systems.

PMID- 9185556
TI  - Memory representation within the parahippocampal region.
AB  - The activity of 378 single neurons was recorded from areas of the parahippocampal
      region (PHR), including the perirhinal and lateral entorhinal cortex, as well as
      the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample
      task. Nearly every neuron fired in association with some trial event, and every
      identifiable trial event or behavior was encoded by neuronal activity in the PHR.
      The greatest proportion of cells was active during odor sampling, and for many
      cells, activity during this period was odor selective. In addition, odor memory
      coding was reflected in two general ways. First, a substantial proportion of
      cells showed odor-selective activity throughout or at the end of the memory delay
      period. Second, odor-responsive cells showed odor-selective enhancement or
      suppression of activity during stimulus repetition in the recognition phase of
      the task. These data, combined with evidence that the PHR is critical for
      maintaining odor memories in animals performing the same task, indicate that this
      cortical region mediates the encoding of specific memory cues, maintains stimulus
      representations, and supports specific match-nonmatch judgments critical to
      recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or
      maintained stimulus-specific codings, and hippocampal damage results in little if
      any decrement in performance on this task. Thus it becomes increasingly clear
      that the parahippocampal cortex can support recognition memory independent of the
      distinct memory functions of the hippocampus itself.

PMID- 9185557
TI  - Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced
      CA1 long-term potentiation (LTP) but normal CA3 LTP.
AB  - Class I metabotropic glutamate receptors (mGluRs) have been postulated to play a
      role in synaptic plasticity. To test the involvement of one member of this class,
      we have recently generated mutant mice that express no mGluR5 but normal levels
      of other glutamate receptors. The CNS revealed normal development of gross
      anatomical features. To examine synaptic functions we measured evoked field EPSPs
      in the hippocampal slice. Measures of presynaptic function, such as paired pulse
      facilitation in mutant CA1 neurons, were normal. The response of mutant CA1
      neurons to low concentrations of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic
      acid (ACPD) was missing, which suggests that mGluR5 may be the primary high
      affinity ACPD receptor in these neurons. Long-term potentiation (LTP) in mGluR5
      mutants was significantly reduced in the NMDA receptor (NMDAR)-dependent pathways
      such as the CA1 region and dentate gyrus of the hippocampus, whereas LTP remained
      intact in the mossy fiber synapses on the CA3 region, an NMDAR-independent
      pathway. Some of the difference in CA1 LTP could lie at the level of expression,
      because the reduction of LTP in the mutants was no longer observed 20 min after
      tetanus in the presence of 2-amino-5-phosphonopentanoate. We propose that mGluR5
      plays a key regulatory role in NMDAR-dependent LTP. These mutant mice were also
      impaired in the acquisition and use of spatial information in both the Morris
      water maze and contextual information in the fear-conditioning test. This is
      consistent with the hypothesis that LTP in the CA1 region may underlie spatial
      learning and memory.

PMID- 9185558
TI  - Recovery of neurofilament expression selectively in regenerating reticulospinal
      neurons.
AB  - During regeneration of lamprey spinal axons, growth cones lack filopodia and
      lamellipodia, contain little actin, and elongate much more slowly than do typical
      growth cones of embryonic neurons. Moreover, these regenerating growth cones are
      densely packed with neurofilaments (NFs). Therefore, after spinal hemisection the
      time course of changes in NF mRNA expression was correlated with the probability
      of regeneration for each of 18 identified pairs of reticulospinal neurons and 12
      cytoarchitectonic groups of spinal projecting neurons. During the first 4 weeks
      after operation, NF message levels were reduced dramatically in all axotomized
      reticulospinal neurons, on the basis of semiquantitative in situ hybridization
      for the single lamprey NF subunit (NF-180). Thereafter, NF expression returned
      toward normal in neurons whose axons normally regenerate beyond the transection
      but remained depressed in poorly regenerating neurons. The recovery of NF
      expression in good regenerators was independent of axon growth across the lesion,
      because excision of a segment of spinal cord caudal to the transection site
      blocked regeneration but did not prevent the return of NF-180 mRNA. The early
      decrease in NF mRNA expression was not accompanied by a reduction in NF protein
      content. Thus the axotomy-induced loss of most of the axonal volume resulted in a
      reduced demand for NF rather than a reduction in volume-specific NF synthesis. We
      conclude that the secondary upregulation of NF message during axonal regeneration
      in the lamprey CNS may be part of an intrinsic growth program executed only in
      neurons with a strong propensity for regeneration.

PMID- 9185559
TI  - Role of neural cell adhesion molecule and polysialic acid in mouse circadian
      clock function.
AB  - The suprachiasmatic nuclei (SCN) express the highly polysialylated form of the
      neural cell adhesion molecule (NCAM) that has been proposed to promote plasticity
      in the adult brain. To investigate a role for NCAM in SCN circadian clock
      function, we examined the daily locomotor rhythm of mice homozygous for a
      mutation, Ncamtm1Cwr, which results in deletion of the NCAM-180 isoform that in
      brain carries polysialic acid (PSA). Mutant mice entrained well to a 12 hr
      light/dark cycle but exhibited a significantly shortened free-running period and
      longer activity duration under constant darkness (DD) than did wild-type mice. By
      the third week of DD treatment, circadian rhythmicity in the mutant was
      abolished. Immunocytochemical analyses of the mutant SCN revealed an abnormal
      number and distribution of vasoactive intestinal polypeptide-producing neurons,
      suggesting a developmental effect of the mutant phenotype; however, a direct
      physiological effect of the mutation on clock function was indicated by the fact
      that removal of PSA from adult wild-type SCN by microinjection of
      endoneuraminidase shortened the free-running period to a similar extent as in the
      mutant. Together, these data indicate critical roles for NCAM and PSA in the
      development and physiology of the mammalian SCN circadian clock.

PMID- 9185560
TI  - Disruption of decrements in conditioned stimulus processing by selective removal
      of hippocampal cholinergic input.
AB  - The attention directed to environmental stimuli can be modified by experience.
      For example, preexposure of a conditioned stimulus (CS) in the absence of
      reinforcement can retard subsequent conditioning of that stimulus when it is
      paired directly with an unconditioned stimulus, a phenomenon referred to as
      latent inhibition. Similarly, consistent pairings of a CS with another event can
      slow the acquisition of new information about that CS. Such phenomena suggest
      that reductions in the processing of CSs occur when they are made behaviorally
      irrelevant or consistent predictors of other events. On the basis of the
      observation that hippocampal lesions prevented such reductions in CS processing,
      we hypothesized that damage to basal forebrain cholinergic neurons that project
      to the hippocampus, using microinjections of the selective immunotoxin 192 IgG
      saporin into the medial septum/vertical limb of the diagonal band (MS/VDB), also
      would disrupt normal reductions in CS processing. Lesions of hippocampal
      cholinergic input disrupted decreases in CS processing, manifested in both an
      absence of latent inhibition and a lack of reduced processing of a CS that had
      been a consistent predictor of another CS. These results indicate that
      cholinergic neurons in the MS/VDB play a role in the regulation of CS processing.
      Furthermore, these findings (in conjunction with previous findings) implicate
      both rostral (hippocampal-projecting) and caudal (cortical-projecting) regions of
      the basal forebrain cholinergic system in the modulation of attention.

PMID- 9185561
TI  - Amygdalar lesions block discriminative avoidance learning and cingulothalamic
      training-induced neuronal plasticity in rabbits.
AB  - Learning to fear dangerous situations requires the participation of neurons of
      the amygdala. Here it is shown that amygdalar neurons are also involved in
      learning to avoid dangerous situations. Amygdalar lesions severely impaired the
      acquisition of acoustically cued, discriminative instrumental avoidance behavior
      of rabbits. In addition, the development of anterior cingulate cortical and
      medial dorsal thalamic training-induced neuronal plasticity in the early stages
      of behavioral acquisition was blocked in rabbits with lesions. The development of
      training-induced neuronal plasticity in the medial dorsal and anterior thalamic
      nuclei in late stages of behavioral acquisition was also blocked in rabbits with
      lesions. These results indicate that the integrity of the amygdala is essential
      for the establishment of both early and late training-induced cingulothalamic
      neuronal plasticity. It is hypothesized that amygdalar training-induced neuronal
      plasticity in the initial trials of conditioning represents a substrate of
      learned fear, essential for the early and late cingulothalamic plasticity that is
      involved in mediation of acquisition of the instrumental avoidance response.

PMID- 9185562
TI  - Lesions in medial preoptic area and bed nucleus of stria terminalis: differential
      effects on copulatory behavior and noncontact erection in male rats.
AB  - The goal of these studies was to assess the regulatory roles of the medial
      preoptic area (MPOA) and the bed nucleus of the stria terminalis (BST) in sexual
      arousal, inferred from noncontact erection (NCE) evoked in male rats by remote
      cues from estrous females. NCE and copulatory behavior were recorded before and
      after quinolinic acid or radiofrequency (RF) lesions were made in the MPOA
      (Experiments 1-3) or RF lesions were made in the BST (Experiment 4). All males
      with MPOA lesions, particularly in the rostral region, displayed severe deficits
      in copulation but little or no decrement in NCE. In contrast, BST lesions caused
      relatively moderate deficits in copulation, but they severely impaired NCE.
      Animals with larger BST lesions, including rostral and caudal medial regions, had
      more deficits in both copulatory behavior and NCE than did males with smaller
      lesions confined to the rostral medial BST. These results suggest that (1) the
      MPOA is critical for copulatory behavior but not for NCE, (2) males that stop
      copulating after MPOA lesions are still sexually aroused by estrous females, and
      (3) the BST plays an important role in mediating NCE.

PMID- 9185564
TI  - RNA base-amino acid interaction strengths derived from structures and sequences.
AB  - We investigate RNA base-amino acid interactions by counting their contacts in
      structures and their implicit contacts in various functional sequences where the
      structures can be assumed to be preserved. These frequencies are cast into
      equations to extract relative interaction energetics. Previously we used this
      approach in considering the major groove interactions of DNA, and here we apply
      it to the more diverse interactions observed in RNA. Structures considered are
      the three different tRNA synthetase complexes, the U1A spliceosomal protein with
      an RNA hairpin and the BIV TAR-Tat complex. We use binding data for the base
      frequencies for the seryl, aspartyl and glutaminyl tRNA-synthetase and U1 RNA
      protein complexes. We compare with the previously reported DNA major groove
      peptide contacts the results for atoms of RNA bases, usually in the major groove.
      There are strong similarities between the rank orders of interacting bases in the
      DNA and the RNA cases. The apparent strongest RNA interaction observed is between
      arginine and guanine which was also one of the strongest DNA interactions. The
      similar data for base atomic interactions, whether base paired or not, support
      the importance of strong atomic interactions over local structure considerations,
      such as groove width and alpha-helicity.

PMID- 9185565
TI  - Identification of sigma factors for growth phase-related promoter selectivity of
      RNA polymerases from Streptomyces coelicolor A3(2).
AB  - We examined the promoter selectivity of RNA polymerase (RNAP) from Streptomyces
      coelicolor at two growth phases by in vitro transcription. Distinct sets of
      promoters were preferentially recognized by either exponential or stationary
      phase RNAP. No change in molecular weight or net charge of the core subunits was
      observed, suggesting that the associated specificity factors determined phase
      specific promoter selectivity of the holoenzyme. Five different specificity
      factors and their cognate promoters were identified by in vitro holoenzyme
      reconstitution and transcription assays. sigma66 (sigma hrdB) and sigma46 (sigma
      hrdD) recognized promoters (rrnD p2 and dagA p4 for sigma66, actII-orf4 p and
      whiB p2 for sigma46) preferentially transcribed by the exponential phase RNAP.
      sigma52 recognized promoters (dagA p3 and actIII px1) preferentially transcribed
      by the stationary phase RNAP. Sigma28 (sigma sigE) recognized promoters (hrdD p1,
      whiB p1 and dagA p2) transcribed equally by both RNAPs. A novel 31 kDa
      specificity factor recognized actIII px2, glnR p2 and hrdD p2 promoters
      preferentially transcribed by the stationary phase RNAP. This factor was isolated
      from the stationary phase RNAP and reconstituted holoenzyme in vitro as a sigma
      factor. The N-terminal sequence suggests that it is a novel factor. By examining
      phase-specific promoter recognition pattern we can predict that holoenzyme
      Esigma52 and Esigma31 activities are higher in the stationary phase, whereas
      Esigma66 and Esigma46activities are higher in the exponential phase. Possible
      promoter sequences recognized by some of these sigma factors were suggested.

PMID- 9185567
TI  - Visualization of RNA crystal growth by atomic force microscopy.
AB  - The crystallization of transfer RNA (tRNA) was investigated using atomic force
      microscopy (AFM) over the temperature range from 4 to 16 degrees C, and this
      produced the first in situ AFM images of developing nucleic acid crystals. The
      growth of the (110) face of hexagonal yeast tRNAPhe crystals was observed to
      occur at steps on vicinal hillocks generated by multiple screw dislocation
      sources in the temperature range of 13.5-16 degrees C. Two-dimensional nucleation
      begins to dominate at 13.5 degrees C, with the appearance of three-dimensional
      nuclei at 12 degrees C. The changes in growth mechanisms are correlated with
      variations in supersaturation which is higher in the low temperature range.
      Growth of tRNA crystals was characterized by a strong anisotropy in the
      tangential step movement and transformation of growth modes on single crystals
      were directly observed by AFM over the narrow temperature range utilized.
      Finally, lattice resolution images of the molecular structure of surface layers
      were recorded. The implications of the strong temperature dependence of tRNAPhe
      crystal growth are discussed in view of improving and better controlling
      crystallization of nucleic acids.

PMID- 9185566
TI  - A macrocyclic bis-acridine shifts the equilibrium from duplexes towards DNA
      hairpins.
AB  - Nucleic acids can undergo dynamic conformational changes associated with the
      regulation of biological processes. A molecule presenting larger affinities for
      alternative structures relative to a duplex is expected to modify such
      conformational equilibria. We have previously reported that macrocyclic bis
      acridine binds preferentially to single-stranded regions, especially DNA
      hairpins, due to steric effects. Here, we show, using gel electrophoresis,
      fluorescence and melting temperature experiments, that the macrocycle bis
      acridine shifts an equilibrium from a duplex towards the corresponding hairpins.
      Competition experiments enlighten the higher affinity of the macrocycle for
      hairpins compared with double-stranded DNA. The macrocycle bis-acridine
      destabilizes a synthetic polynucleotide, by the formation of premelted areas. By
      extrapolation, the macrocycle bis-acridine should be able to disrupt, at least
      locally, genomic DNA duplexes and to stabilize unpaired areas, especially
      palindromic ones forming hairpins. Such macrocyclic compounds may have potential
      applications in the therapy of diseases involving hairpins.

PMID- 9185563
TI  - Alternative poly(A) site selection in complex transcription units: means to an
      end?
AB  - Many genes have been described and characterized which result in alternative
      polyadenylation site use at the 3'-end of their mRNAs based on the cellular
      environment. In this survey and summary article 95 genes are discussed in which
      alternative polyadenylation is a consequence of tandem arrays of poly(A) signals
      within a single 3'-untranslated region. An additional 31 genes are described in
      which polyadenylation at a promoter-proximal site competes with a splicing
      reaction to influence expression of multiple mRNAs. Some have a composite
      internal/terminal exon which can be differentially processed. Others contain
      alternative 3'-terminal exons, the first of which can be skipped in some cells.
      In some cases the mRNAs formed from these three classes of genes are
      differentially processed from the primary transcript during the cell cycle or in
      a tissue-specific or developmentally specific pattern. Immunoglobulin heavy chain
      genes have composite exons; regulated production of two different Ig mRNAs has
      been shown to involve B cell stage-specific changes in trans -acting factors
      involved in formation of the active polyadenylation complex. Changes in the
      activity of some of these same factors occur during viral infection and take-over
      of the cellular machinery, suggesting the potential applicability of at least
      some aspects of the Ig model. The differential expression of a number of genes
      that undergo alternative poly(A) site choice or polyadenylation/splicing
      competition could be regulated at the level of amounts and activities of either
      generic or tissue-specific polyadenylation factors and/or splicing factors.

PMID- 9185568
TI  - The POU-domain factor Brn-3.0 recognizes characteristic sites in the herpes
      simplex virus genome.
AB  - The restriction of herpes virus latency to mammalian sensory ganglia has led to a
      search for tissue-specific regulatory molecules in these neurons which alter
      viral gene expression. We have recently shown that the POU-domain transcriptional
      regulator Brn-3.0 is abundantly expressed in the adult trigeminal ganglion. To
      begin to examine the hypothesis that Brn-3.0 might participate in the regulation
      of the HSV life-cycle, we used Brn-3.0 POU-domain protein as an affinity matrix,
      and biochemically screened the entire HSV genome for sites of Brn-3.0 binding.
      This screen identified several sites of the form TA/TA A T N A N TA/T, which
      significantly do not include the previously identified HSV octamer sequences. All
      of the selected sites occur in the <25% of the HSV genome which has not been
      assigned to open reading frames, suggesting that these sites may be
      transcriptional regulatory elements recognized by Brn-3.0 or another homeobox
      factor with similar DNA binding properties. However, these sites do not interact
      with Brn-3.0 with sufficiently high affinity to directly mediate transcriptional
      activation by Brn-3.0 alone in transfection assays. The experiments described
      also provide an effective general method for exhaustive screening of large viral
      genomes or sub-genomic fragments of eukaryotic DNA for sites of interaction with
      specific transcription factors.

PMID- 9185569
TI  - Advances in quantification and characterization of telomerase activity by the
      telomeric repeat amplification protocol (TRAP).
AB  - The telomeric repeat amplification protocol (TRAP) assay has been used to test
      telomerase activity in numerous cancer specimens. We describe primers, controls
      and quantification methods for the TRAP assay to accurately measure the level of
      telomerase activity in clinical samples. The assay is reliable and reproducible
      in routine analyses and can be used to estimate the processivity of telomerase
      activity.

PMID- 9185570
TI  - A high throughput screening for rarely transcribed differentially expressed
      genes.
AB  - A novel method combining elements of suppression subtractive hybridization with
      high throughput differential screening permits the efficient and rapid cloning of
      rarely transcribed differentially expressed genes. The experimental strategy
      virtually excludes the possibility of isolating false positive clones. The
      potential of the method is demonstrated by the isolation of 625 differentially
      expressed cDNAs from the metastatic adenocarcinoma cell line Bsp73-ASML when
      subtracted from its non-metastatic counterpart Bsp73-1AS. Northern analysis of 72
      randomly selected clones demonstrated that 68 were differentially expressed with
      respect to Bsp73-ASML, indicating a true positive rate of 94%. Additionally, a
      large proportion of these clones represented rare transcripts as determined by
      the exposure time required to detect a signal. Sequence data indicated that of
      the 625 clones obtained, 92 clones scored perfect or near perfect matches with
      already known genes. Two hundred and eighty one clones scored between 60 and 95%
      homology to known human and mouse genes, whereas 252 clones scored no match with
      any sequences in the public databases. The method we describe is ideally suited
      whenever subtle changes in gene expression profiles need to be determined.

PMID- 9185571
TI  - sigma factor mutations affecting the sequence-selective interaction of RNA
      polymerase with -10 region single-stranded DNA.
AB  - Thesigmasubunit of RNA polymerase determines promoter recognition and catalyzes
      DNA strand separation. The -35 promoter region is recognized by a helix-turn
      helix motif in region 4, while the -10 region is specified, at least in part, by
      an amphipathic helix in region 2. We have proposed that conserved aromatic
      residues insigmaregion 2.3 interact with the non-template strand of the -10
      element to drive open complex formation. We now report that Bacillus subtilis
      sigmaA holoenzyme, but neither core nor sigmaA alone, binds with high selectivity
      to single-stranded (ss) DNA containing the non-template -10 consensus sequence.
      UV irradiation of holoenzyme-ssDNA complexes efficiently crosslinks sigmaA to DNA
      and protease mapping supports a primary contact site in or near region 2. Several
      mutations in sigmaA region 2.3, shown previously to impair promoter melting,
      affect ssDNA binding: Y184A decreases binding selectivity, while Y189A and W193A
      decrease the efficiency of photocrosslinking. These results support a model in
      which these aromatic amino acids are juxtaposed to ssDNA, consistent with their
      demonstrated role in stabilizing the open complex.

PMID- 9185572
TI  - Evolutionarily conserved and functionally important residues in the I-CeuI homing
      endonuclease.
AB  - Two approaches were used to discern critical amino acid residues for the function
      of the I- Ceu I homing endonuclease: sequence comparison of subfamilies of
      homologous proteins and genetic selection. The first approach revealed residues
      potentially involved in catalysis and DNA recognition. Because I- Ceu I is lethal
      in Escherichia coli , enzyme variants not perturbing cell viability were readily
      selected from an expression library. A collection of 49 variants with single
      amino acid substitutions at 37 positions was assembled. Most of these positions
      are clustered within or around the LAGLI-DADG dodecapeptide and the TQH sequence,
      two motifs found in all protein subfamilies examined. The Km and kcat values of
      the wild-type and nine variant enzymes synthesized in vitro were determined.
      Three variants, including one showing a substitution of the glutamine residue in
      the TQH motif, revealed no detectable endonuclease activity; five others showed
      reduced activity compared to the wild-type enzyme; whereas the remaining variant
      cleaved the top strand about three times more efficiently than the wild-type. Our
      results not only confirm recent reports indicating that amino acids in the LAGLI
      DADG dodecapeptide are functionally critical, but they also suggest that some
      residues outside this motif directly participate in catalysis.

PMID- 9185573
TI  - Characterization and crystallization of the helicase domain of bacteriophage T7
      gene 4 protein.
AB  - Limited proteolysis of bacteriophage T7 primase/helicase with endoproteinase Glu
      C produces several proteolytic fragments. One of these fragments, which is
      derived from the C-terminal region of the protein, was prepared and shown to
      retain helicase activity. This result supports a model in which the gene 4
      proteins consist of functionally separable domains. Crystals of this C-terminal
      fragment of the protein have been obtained that are suitable for X-ray
      diffraction studies.

PMID- 9185574
TI  - Conformational properties and thermodynamics of the RNA duplex r(CGCAAAUUUGCG)2:
      comparison with the DNA analogue d(CGCAAATTTGCG)2.
AB  - The thermodynamic stability of nine dodecamers (four DNA and five RNA) of the
      same base composition has been compared by UV-melting. TheDeltaG of stabilisation
      were in the order: r(GACUGAUCAGUC)2>r(CGCAAATTTGCG)2 approximately
      r(CGCAUAUAUGCG)2>d(CGCAAATTTGCG)2 approximately r(CGCAAAUUUGCG)2>d(CGCATATATGCG)2
      approximately d(GACTGATCAGTC)2>r(CGCUUUAAAGCG)2 approximately d(CGCTTTAAAGCG)2.
      Compared with the mixed sequences, both r(AAAUUU) and r(UUUAAA) are greatly
      destablising in RNA, whereas in DNA, d(TTTAAA) is destabilising but d(AAATTT) is
      stabilising, which has been attributed to the formation of a special B'structure
      involving large propeller twists of the A-T base pairs. The solution structure of
      the RNA dodecamer r(CGCAAAUUUGCG)2has been determined using NMR and restrained
      molecular dynamics calculations to assess the conformational reasons for its
      stability in comparison with d(CGCAAATTTGCG)2. The structures refined to a mean
      pairwise r.m.s.d. of 0.89+/-0.29 A. The nucleotide conformations are typical of
      the A family of structures. However, although the helix axis displacement is
      approximately 4.6 A into the major groove, the rise (3.0 A) and base inclination
      ( approximately 6 degrees ) are different from standard A form RNA. The extensive
      base-stacking found in the AAATTT tract of the DNA homologue that is largely
      responsible for the higher thermodynamic stability of the DNA duplex is reduced
      in the RNA structure, which may account for its low relative stability.

PMID- 9185576
TI  - Physical interference between escherichia coli RNA polymerase molecules
      transcribing in tandem enhances abortive synthesis and misincorporation.
AB  - Transcription initiation is accompanied with iterative synthesis and release of
      short transcripts. The molar ratio of enzyme to template was found to be critical
      for the amounts and distribution of the abortive products synthesized by
      Escherichia coli RNA polymerase from several promoters. At a high ratio abortive
      synthesis of 4-8 nt were enhanced at thelambda P R promoter. Removing excess RNA
      polymerase just before initiation, achieved by washing immobilized transcription
      complexes, prevented this enhancement. At this high ratio synthesis of an
      unexpected 6 nt transcript was enhanced when the enzyme stalled at position +32,
      but not when it stalled at position +73. This transcript had misincorporations at
      its fifth and sixth positions, probably due to slippage. Hydroxyl radical
      footprinting of the complex stalled at +32 in the presence of excess enzyme
      showed that more than one molecule of RNA polymerase was tandemly bound to the
      same DNA. These results suggest that: (i) when RNA polymerase molecules are
      tandemly transcribing the same DNA, transient collisions enhance abortive
      synthesis by the trailing molecule; (ii) when the leading polymerase stalled in
      the initially transcribed region blocks progression of the trailing polymerase,
      the latter can commit misincorporations, probably due to slippage synthesis.

PMID- 9185575
TI  - Analysis of chromatin structure of rat alpha1-acid glycoprotein gene; changes in
      DNase I hypersensitive sites after thyroid hormone, glucocorticoid hormone and
      turpentine oil treatment.
AB  - Transcription of the ratalpha1-acid glycoprotein (AGP) gene is activated by
      glucocorticoid, thyroid hormone (T3) and cytokines. Following these treatments,
      the chromatin structure of this gene was analyzed by means of digestion with
      DNase I or micrococcal nuclease. Four DNase I hypersensitive sites were observed
      in the 5'-upstream region of the rat AGP gene of liver cells. They were
      designated HS1, HS2, HS3 and HS4 (3'-->5'). After T3treatment the sensitivity of
      HS1 and HS2 increased and after dexamethasone (Dex) treatment that of all four
      sites did so. Three new sites appeared after turpentine oil treatment, while the
      sensitivities of HS3 and HS4 increased. We conclude that transcriptional
      activation of the gene by T3and Dex have very similar mechanisms, but that at the
      inflammation stage they become slightly different. The increase in sensitivity at
      HS1 and HS2 after T3treatment in vivo was successfully reproduced in a cell-free
      system by in vitro treatment with T3. HS1, HS2 and HS3 were also sensitive for
      micrococcal nuclease.

PMID- 9185577
TI  - Formation of a G-tetrad and higher order structures correlates with biological
      activity of the RelA (NF-kappaB p65) 'antisense' oligodeoxynucleotide.
AB  - We have examined the behavior of the phosphorothioate antisense Rel A (NF-kappaB
      p65) oligodeoxynucleotide (oligo) and related molecules. Because of the presence
      of a G-tetrad near its 5'terminus, this molecule is capable of forming
      tetraplexes and other higher order structures in a temperature and time dependent
      manner. The G-tetrad in the phosphodiester congener is protected from methylation
      by dimethylsulfate when the oligomer is 3'-phosphorylated. However, this
      protection is completely lost when it is 5'phosphorylated, indicating that the
      formation of at least some higher order structures has been blocked. In addition,
      we also prevented tetraplex formation by substitution of 7-deazaguanosine (7-DG)
      for guanosine at several positions within and outside of the tetrad. This
      substitution retains Watson-Crick base pair hybridization but prevents Hoogsteen
      base-pair interactions. When murine K-Balb cells were treated with 20microM
      antisense RelA oligo, complete blockade of nuclear translocation of RelA was
      observed. However, this effect was virtually entirely abrogated in most cases by
      7-DG substitution within the tetrad, but retained when the substitution was made
      3' to the tetrad. The AS RelA-induced downregulation of Sp-1 activity behaved
      similarly after 7-DG substitution. Thus, the parent phosphorothioate AS RelA
      molecule cannot be a Watson-Crick antisense agent. However, these conclusions
      cannot be extrapolated to other G-tetrad containing oligomers and each must be
      evaluated individually.

PMID- 9185578
TI  - Efficient priming of PCR with short oligonucleotides conjugated to a minor groove
      binder.
AB  - The tripeptide 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3) binds
      to the minor groove of DNA with high affinity. When this minor groove binder
      (MGB) is conjugated to the 5'-end of short oligodeoxynucleotides (ODNs), the
      conjugates form unusually stable hybrids with complementary DNA in which the
      tethered CDPI3group resides in the minor groove. We show that these conjugates
      can be used as PCR primers. Due to their unusually high binding affinity,
      conjugates as short as 8-10mers can be used to amplify DNA with good specificity
      and efficiency. The reduced length primers described here might be appropriate
      for the PCR amplification of viral sequences which possess a high degree of
      variability (e.g., HPV, HIV) or for recent techniques such as gene hunting and
      differential display which amplify multiple sequences using short primer pairs.

PMID- 9185579
TI  - Identification and characterization of the human XIST gene promoter: implications
      for models of X chromosome inactivation.
AB  - The XIST gene in both humans and mice is expressed exclusively from the inactive
      X chromosome and is required for X chromosome inactivation to occur early in
      development. In order to understand transcriptional regulation of the XIST gene,
      we have identified and characterized the human XIST promoter and two repeated DNA
      elements that modulate promoter activity. As determined by reporter gene
      constructs, the XIST minimal promoter is constitutively active at high levels in
      human male and female cell lines and in transgenic mice. We demonstrate that this
      promoter activity is dependent in vitro upon binding of the common transcription
      factors SP1, YY1 and TBP. We further identify two cis -acting repeated DNA
      sequences that influence reporter gene activity. First, DNA fragments containing
      a set of highly conserved repeats located within the 5'-end of XIST stimulate
      reporter activity 3-fold in transiently transfected cell lines. Second, a 450 bp
      alternating purine-pyrimidine repeat located 25 kb upstream of the XIST promoter
      partially suppresses promoter activity by approximately 70% in transient
      transfection assays. These results indicate that the XIST promoter is
      constitutively active and that critical steps in the X inactivation process must
      involve silencing of XIST on the active X chromosome by factors that interact
      with and/or recognize sequences located outside the minimal promoter.

PMID- 9185581
TI  - Recovery of YAC-end sequences through complementation of an Escherichia coli pyrF
      mutation.
AB  - We have developed a genetic means to recover sequences from YAC-ends near the
      yeast selectable marker URA3. This strategy is based on the ability of URA3 to
      complement mutations in pyrF, an Escherichia coli gene required for pyrimidine
      biosynthesis. We have developed an E.coli strain with a non-reverting allele of
      pyrF that is also suitable for cloning (recA-, hsdR-). We demonstrate the utility
      of this complementation strategy to obtain right-end clones from three YACs
      containing Arabidopsis thaliana DNA.

PMID- 9185580
TI  - Characterization and mapping of the double-stranded regions involved in
      activation of PKR within a cellular RNA from 3T3-F442A cells.
AB  - PKR is a doubled-stranded RNA-dependent protein kinase which is implicated in the
      regulation of several cellular processes, including cell proliferation. PKR
      undergoes phosphorylation and activation in mouse embryonic 3T3-F442A cells in
      response to endogenous RNA(s). Activation of PKR is related to growth and
      differentiation of these cells. A cellular regulatory RNA (R-RNA) which activates
      PKR has been isolated from these cells and its cDNA partially sequenced. Here we
      have characterized the R-RNA transcript with respect to nuclease sensitivity and
      the extent of double-stranded structure involved in activation of PKR. The
      location of the activating sequence was mapped to a contiguous 226/252 nt region
      of the R-RNA transcript by hybridization to its cDNA fragments. Hybridization
      with a panel of short oligodeoxynucleotides complementary to the R-RNA, coupled
      with protein kinase analysis, was used to probe the 252 nt region for critical
      sequences. Three short non-contiguous sequences which appear most important for
      activation of PKR were identified within the 252 nt region. Thus, these studies
      have identified specific sequences most important for activation of PKR.
      Furthermore, since the above antisense oligodeoxynucleotides inhibit enzyme
      activation, our results exemplify an unusual mode of action of antisense
      sequences on the activation of PKR by disruption of RNA secondary structure.

PMID- 9185582
TI  - Isolation of rare transcripts by representational difference analysis.
AB  - Representational difference analysis (RDA) is a powerful technique for cloning
      the differences between genomes, and has recently been adapted for cloning
      differentially expressed genes. RDA, like other PCR-based differential screening
      methods, is prone to the production of false positives. We have identified a
      major source of false positives in RDA of cDNA and have introduced improvements
      which minimise their production. These modifications also significantly increase
      sensitivity, allowing for the isolation of rare differential transcripts from
      nanogram amounts of mRNA.

PMID- 9185583
TI  - Construction and characterization of a replication-defective herpes simplex virus
      2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of
      genital disease.
AB  - A replication-defective mutant of herpes simplex virus 2 (HSV-2) was engineered
      by replacing the ICP8 gene of HSV-2 strain 186 with an ICP8-lacZ fusion gene from
      the herpes simplex virus 1 (HSV-1) HD-2 mutant strain. The resulting virus, HSV-2
      5BlacZ, is defective for growth in Vero cells but is capable of growth in a cell
      line that expresses HSV-1 ICP8. In Vero cells, the mutant virus is defective for
      DNA synthesis but is able to express many viral proteins at levels similar to
      those of wild-type virus, including several of the late kinetic class. SDS-PAGE
      and Western blot analysis demonstrated the expression of glycoproteins B and D by
      5BlacZ in Vero cells. Initial studies have shown that immunization with 5BlacZ
      protects guinea pigs from intravaginal HSV-2 challenge. Immunized animals had
      less severe genital skin disease and reduced replication of the challenge virus
      in the genital tract during primary infection and reduced episodes of recurrent
      disease. Thus, HSV-2 ICP8 shows gene regulatory properties similar to those of
      HSV-1 ICP8, and this HSV-2 ICP8 mutant virus shows a phenotype similar to those
      of HSV-1 ICP8 mutant strains. Replication-defective mutants of HSV-2 offer a
      potential vaccine approach for immune intervention against HSV-2 genital disease
      and latent infection.

PMID- 9185584
TI  - Second-site reversion of a dysfunctional mutation in a conserved region of the
      tobacco mosaic tobamovirus movement protein.
AB  - The N-terminal two-thirds of tobamovirus movement proteins (MPs) contain two well
      conserved regions. Within region I (amino acids 56-96) is an area predicted by
      computer analysis to have loop secondary structure (amino acids 76-87). A single
      or two double amino acid mutations were introduced into the loop in region I of
      the TMV MP to destabilize the structure. The three mutant MPs were defective in
      movement function. The single amino acid mutation resulted in a Pro81-->Ser
      substitution. The mutant virus, TP81S, containing the Pro81-->Ser substitution,
      was propagated on a transgenic line of Nicotiana tabacum that expresses the sunn
      hemp mosaic tobamovirus MP. Inoculation of virus progeny from the transgenic
      plants onto hypersensitive N. tabacum indicated the presence of infectious virus
      at a low frequency. Necrotic lesions were detected at 4 days postinoculation, 2
      days later than those induced by wild-type TMV. Inoculation of virus extracted
      from necrotic lesions onto N. tabacum resulted in a delayed and attenuated
      systemic infection relative to that induced by TMV, indicating that a second-site
      mutation restored movement function rather than a reversion of the original
      mutation. Sequence analysis revealed that the revertant MP gene had two
      additional amino acid substitutions, a Thr104-->Ile and a Arg167-->Lys.
      Introduction of the amino acid substitutions individually or in combination into
      the MP of TP81S indicated that both substitutions were required for the revertant
      phenotype. The data indicate that structure within region I is important in
      maintaining an active conformation for functional MP, that changes outside region
      I can compensate for alterations within the region, and suggest that region I may
      interact with a distal portion of the protein.

PMID- 9185585
TI  - Binding of the influenza A virus to cell-surface receptors: structures of five
      hemagglutinin-sialyloligosaccharide complexes determined by X-ray
      crystallography.
AB  - The structures of five complexes of the X-31 influenza A (H3N2) virus
      hemagglutinin with sialyloligosaccharide receptor analogs have been determined
      from 2.5 to 2.8 A resolution by X-ray crystallography. There is well-defined
      electron density for three to five saccharides in all five complexes and a
      striking conformational difference between two linear pentasaccharides with the
      same composition but different linkage [alpha(2-->6) or alpha(2-->3)] at the
      terminal sialic acid. The bound position of the terminal sialic acid (NeuAc) is
      the same in all five complexes and is identical to that reported previously from
      the study of mono- and trisaccharides. The two oligosaccharides with NeuAc
      alpha(2-->6)Gal linkages and GlcNAc at the third position have a folded
      conformation with the GlcNAc doubled back to contact the sialic acid. The
      pentasaccharide with a terminal NeuAc alpha(2-->3)Gal linkage and GlcNAc at the
      third position has an extended (not folded) conformation and exits from the
      opposite side of the binding site than the alpha(2-->6)-linked molecule of the
      same composition. The difference between the conformation of the pentasaccharide
      with a 2,6 linkage and the trisaccharide 2,6-sialyllactose suggests that 2,6
      sialyllactose is not, as previously believed, an appropriate analog of natural
      influenza A virus receptors. The oligosaccharides studied are NeuAc alpha(2-
      >3)Gal beta(1-->4)Glc, NeuAc alpha(2-->6)Gal beta(1-->4)Glc, NeuAc alpha(2-
      >3)Gal beta(1-->3)GlcNAc beta(1-->3)Gal beta(1-->4)Glc, NeuAc alpha(2-->6)Gal
      beta(1-->4)GlcNAc beta(1-->3)Gal beta(1-->4)Glc, and [NeuAc alpha(2-->6)Gal
      beta(1-->4)GlcNAc]2 beta(1-->3/6)Gal-beta-O-(CH2)5-COOCH3.

PMID- 9185586
TI  - A tobamovirus genome that contains an internal ribosome entry site functional in
      vitro.
AB  - Most eukaryotic mRNAs are translated by a "scanning ribosome" mechanism. We have
      found that unlike the type member of the genus Tobamovirus, translation of the 3'
      proximal coat protein (CP) gene of a crucifer infecting tobamovirus (crTMV)
      (Dorokhov et al., 1993; 1994) occurred in vitro by an internal ribosome entry
      mechanism. Three types of synthetic dicistronic RNA transcripts were constructed
      and translated in vitro: (i) "MP-CP-3'NTR" transcripts contained movement protein
      (MP) gene, CP gene and the 3'-nontranslated region of crTMV RNA. These constructs
      were structurally equivalent to dicistronic subgenomic RNAs produced by
      tobamoviruses in vivo. (ii) "deltaNPT-CP" transcripts contained partially
      truncated neomycin phosphotransferase I gene and CP gene. (iii) "CP-GUS"
      transcripts contained the first CP gene and the gene of Escherichia coli beta
      glucuronidase (GUS) at the 3'-proximal position. The results indicated that the
      148-nt region upstream of the CP gene of crTMV RNA contained an internal ribosome
      entry site (IRES(CP)) promoting internal initiation of translation in vitro.
      Dicistronic IRES(CP), containing chimeric mRNAs with the 5'-terminal stem-loop
      structure preventing translation of the first gene (MP, deltaNPT, or CP),
      expressed the CP or GUS genes despite their 3'-proximal localization. The
      capacity of crTMV IRES(CP) for mediating internal translation distinguishes this
      CP tobamovirus from the well-known-type member of the genus, TMV UI. The
      equivalent 148-nt sequence from TMV RNA was incapable of mediating internal
      translation. Two mutants were used to study structural elements of IRES(CP). It
      was concluded that integrity of IRES(CP) was essential for internal initiation.
      The crTMV provides a new example of internal initiation of translation, which is
      markedly distinct from IRESs shown for picornaviruses and other viral and
      eukaryotic mRNAs.

PMID- 9185587
TI  - Elevated expression of the human parainfluenza virus type 1 F gene downregulates
      HN expression.
AB  - Interactions involved in the expression of parainfluenza glycoproteins were
      examined by expressing cDNA clones of the HN and F genes from human parainfluenza
      virus type-1 (hPIV1) or Sendai virus (SV) in recombinant Semliki Forest virus
      (recSFV) or vaccinia-T7 expression vectors. We found that expression of a cloned
      F protein gene of hPIV1 resulted in downregulation of the HN proteins of hPIV1 or
      SV. Compared to the amount of HN expressed in the absence of F, coexpression of
      HN and F led to about 70% reduction in HN. This reduction of HN was observed in
      both total cell lysates and in protein localized on the cell surface. In contrast
      to hPIV1 F, SV F did not suppress the expression of HN. Northern blot analysis
      indicated that similar levels of HN mRNA accumulated in the absence or presence
      of hPIV1 F. The reduction of HN protein expression by hPIV1 F was detectable
      after as little as a 10-min labeling period, suggesting that downregulation
      occurred at the level of translation or at an early stage of protein folding. In
      hPIV1-infected cells, the amount of F protein synthesized was only about 15% of
      that of HN, whereas SV F is expressed at high levels. When the level of F in
      hPIV1-infected cells was artificially increased by recSFV, HN expression was
      suppressed. The reduction of F protein production in hPIV1-infected cells was
      regulated at the level of transcription. Characterization of mRNAs produced in
      hPIV1-infected cells showed that only 20% of the hPIV1 F mRNAs were monocistronic
      transcripts; 80% were bicistronic M-F readthrough mRNAs. Because proteins are
      suggested to be synthesized from only the first cistron of bicistronic mRNA in
      paramyxovirus (T. C. Wong and A. Hirano (1987) J. Virol. 61, 584-589), production
      of F protein is likely suppressed by transcriptional regulation in hPIV1-infected
      cells. These results suggest that F is capable of downregulating the synthesis of
      HN, but that this is normally prevented in hPIV1-infected cells by suppression of
      F protein synthesis by transcriptional regulation.

PMID- 9185588
TI  - Transactivation of prothymosin alpha and c-myc promoters by human papillomavirus
      type 16 E6 protein.
AB  - The human papillomavirus type 16 E6 protein exerts a transforming activity
      through inactivation of tumor suppressor p53. Recently E6 has been shown to have
      additional transforming activities independent of p53. E6 is able to
      transactivate or repress several specific viral promoters. However, underlying
      molecular mechanisms and cellular target genes for the activity are not well
      understood. Using a differential hybridization technique, we identified the
      prothymosin alpha gene as a cellular target of E6 transactivation. E6 was able to
      transactivate the prothymosin alpha promoter in H358 cells lacking p53 and in
      C33A cells harboring a mutant p53 allele. Disruption of the E-box in intron 1 of
      the prothymosin alpha promoter abolished the responsiveness to E6. Then we
      determined if E6 up-regulates the expression of Myc, by which the prothymosin
      alpha promoter is transactivated through the E-box. We found that E6 is also able
      to transactivate the c-myc promoter in H358 cells and in C33A cells. These
      results suggest that E6 is able to transactivate the c-myc promoter independently
      of p53, and that the prothymosin alpha promoter is subsequently transactivated by
      Myc.

PMID- 9185589
TI  - Preferential translation of reovirus mRNA by a sigma3-dependent mechanism.
AB  - We have characterized reovirus strains that differ in the degree to which they
      inhibit cellular protein synthesis and used them to investigate mechanisms
      regulating gene expression in infected cells. A previous genetic study associated
      distinct effects of reovirus strains on cellular translation with polymorphisms
      in viral protein sigma3. In cell extracts, sigma3 sequesters double-stranded RNA
      (dsRNA) and blocks activation of the dsRNA-activated protein kinase (PKR), an
      interferon-induced enzyme that inhibits translational initiation by
      phosphorylating elF-2alpha. We found that in infected cells, cellular protein
      synthesis is translationally regulated in a strain-specific manner. Using
      immunoprecipitation and indirect immunofluorescence we showed that the effect of
      a strain on cellular translation is not determined by the level of sigma3, but
      appears to result from differences in sigma3 localization. In cells infected with
      a strain that spares cellular translation, sigma3 is present throughout the
      cytoplasm, whereas in cells infected with inhibitory strains, sigma3 is
      restricted to perinuclear viral factories. Biochemical studies suggested that
      diffuse localization of sigma3 is a consequence of low affinity for capsid
      protein mu1. Our findings are consistent with a model in which the efficiency of
      cellular translation is determined by the cytoplasmic level of sigma3 that is not
      complexed with mu1.

PMID- 9185590
TI  - A specific host cellular protein binding element near the 3' end of mouse
      hepatitis virus genomic RNA.
AB  - A distinct host cellular protein binding element was mapped within a 38
      nucleotide (nt) sequence 166-129 nucleotides upstream of the 3' end of the MHV
      JHM genome using a RNase T1 protection/gel mobility shift electrophoresis assay.
      The resultant RNA-protein complex contains six host cellular proteins, one
      protein of 120-kDa molecular mass, two poorly resolved species approximately 55
      kDa in size, a second pair of poorly resolved 40-kDa proteins, and a minor
      component of 25 kDa. A series of RNA probes containing deletions or clustered
      transversion mutations were tested for their ability to form complexes with mock-
      and MHV-JHM-infected cytoplasmic extracts. Three mutant RNA probes (mA, mB, and
      mC) with deletions at 154-140, 139-129, and 128-118, respectively, expressed 4,
      37, and 94% of the host protein binding activity exhibited by the wild-type RNA.
      Defective interfering (DI) RNAs (DImA, DImB, and DImC) containing corresponding
      deletions at 154-140, 139-129, 128-118, and another DI RNA (DImD) with a deletion
      at nucleotides (nts) 112-102, a region which did not affect RNA-protein
      interactions, were transfected into MHV-JHM-infected 17CL-1 cells to assay the
      effects of these mutations on DI RNA replication. All of these mutations had an
      adverse effect on DI RNA replication. However, analysis of negative strand mutant
      DI RNAs revealed that two mutants (DImC and DImD) carrying deletions having
      little or no effect on RNA-protein interaction in our RNA-protein binding assays
      maintained their mutant sequences. In contrast, the other two mutants (DImA and
      DImB) containing deletions that dramatically decreased RNA-protein binding
      activity did not maintain their mutations; wild-type sequences were restored in
      the majority of the progeny negative strand molecules. These data indicate that
      the 26-nucleotide sequence at positions 154-129 from the 3' end of viral genome
      is important to both RNA-protein binding and viral replication. This protein
      binding element contains an 11-nt sequence (UGAGAGAAGUU, positions 139-129) very
      similar to a more 3' sequence (UGAAUGAAGUU) previously implicated in host protein
      binding and viral RNA replication (Yu and Leibowitz, 1995a and 1995b).

PMID- 9185591
TI  - Analysis of an interaction between the soluble vaccinia virus-coded type I
      interferon (IFN)-receptor and human IFN-alpha1 and IFN-alpha2.
AB  - The soluble B18R protein coded by vaccinia virus exerts properties of a type I
      interferon (IFN)-receptor with broad species specificity. We analyzed
      neutralizing and binding activity of the B18R protein against several recombinant
      human type I IFNs. The B18R protein inhibited the antiviral potency of IFN
      alpha1, IFN-alpha2, IFN-alpha8/1/8, and IFN-omega on human cells. The N-terminal
      domain of human type I IFN is involved in the high affinity binding to its
      cellular receptor. To localize the binding domain(s) of IFN with the B18R
      protein, competition experiments between B18R, and mapped monoclonal antibodies
      to IFN-alpha1 and IFN-alpha2 were performed. Surprisingly, our data indicated
      that the contact area between the B18R protein and IFN comprised in addition to
      the N-terminal region of IFN-molecule also its C-terminal portion. We suggest
      that this different pattern of interaction with a ligand might determine the
      ability of B18R protein to bind type I IFNs of different species.

PMID- 9185592
TI  - The structure of cucumber mosaic virus: cryoelectron microscopy, X-ray
      crystallography, and sequence analysis.
AB  - The three-dimensional structure of cucumber mosaic virus (CMV) was analyzed at 23
      A resolution by cryoelectron microscopy and image reconstruction, demonstrating
      structural similarity to cowpea chlorotic mottle virus (CCMV), another member of
      the Bromoviridae family. The CMV structure was determined at 8 A resolution by X
      ray crystallography with phases determined by single isomorphous replacement and
      refined by fivefold noncrystallographic symmetry averaging. The X-ray structure
      agreed with the electron microscopy reconstruction; the electron density is
      consistent with beta-barrel subunits arranged with T = 3 quasi-symmetry in an
      orientation similar to that observed in CCMV. Strong density surrounding the
      icosahedral threefold axes (quasi sixfold axes in the T = 3 particle) between 80
      and 100 A from the particle center formed a cylinder of radius 11 A, similar to
      the density observed in the same region of CCMV. This density corresponds to the
      beta-annulus of CCMV, which differentiates hexamers from pentamers and determines
      the formation of the T = 3 particles. The CMV and CCMV amino acid sequences were
      aligned, providing information (based on the CCMV atomic model) about the
      probable distribution of residues in the three-dimensional structure of CMV.

PMID- 9185593
TI  - Challenge of chimpanzees immunized with a recombinant canarypox-HIV-1 virus.
AB  - To evaluate the potential protective efficacy of a live recombinant human
      immunodeficiency virus type 1 (HIV-1) canarypox vaccine candidate, two
      chimpanzees were immunized five times with ALVAC-HIV-1 vCP250, a recombinant
      canarypox virus that expresses the HIV-1[IIIB(LAI)] gp120/TM, gag, and protease
      gene products. One month after the last booster inoculation, the animals were
      challenged by intravenous injection of cell-associated virus in the form of
      peripheral blood mononuclear cells from an HIV-1[IIIB(LAI)]-infected chimpanzee.
      One chimpanzee with a neutralizing antibody titer to HIV-1[IIIB(LAI)] of 128 at
      the time of challenge was protected, whereas both the second animal, with a
      neutralizing antibody titer of 32, and a naive control animal became infected. At
      5 months after challenge, the protected chimpanzee and a third animal, previously
      immunized with various HIV-1[MN] antigens, were given a booster inoculation. The
      two animals were challenged intravenously 5 weeks later with twenty 50% tissue
      culture infectious doses of cell-free HIV-1[DH12], a heterologous subtype B
      isolate. Neither chimpanzee had neutralizing antibodies to HIV-1[DH12], and
      neither one was protected from infection with this isolate. The immune responses
      elicited by vaccination against HIV-1[IIIB(LAI)] or HIV-1[MN] did not, therefore,
      protect the animals from challenge with the heterologous cell-free HIV-1[DH12].

PMID- 9185594
TI  - Cycloheximide inhibition of delayed early gene expression in baculovirus-infected
      cells.
AB  - The baculovirus protein IE1 is required for the transactivation of many early
      viral genes in transient expression assays. However, cycloheximide inhibition
      studies have failed to reveal a dependence of early gene transcription on
      expression of IE1 in infected cells. We show here that synthesis of IE1 was not
      effectively inhibited by the addition of 100 microg/ml cycloheximide, the
      concentration routinely used in these studies. However, when cycloheximide was
      added at 250 microg/ml, IE1 synthesis was repressed to less than 5% of control
      levels. These more stringent conditions were used to discriminate between
      immediate early and delayed early genes. Transcription of three immediate early
      genes (ie1, ie2, and ie0) was increased by the addition of high concentrations of
      cycloheximide. However, transcription of three other early genes (39k, p35, and
      lef-3), which are known to be dependent on IE1 transactivation, was significantly
      reduced by the addition of 250 microg/ml cycloheximide. Immunoblot analyses also
      revealed a difference between the immediate and delayed early class of viral
      genes. Synthesis of IE1, IE2, and IE0 was resistant to cycloheximide treatment,
      while translation of SSB/LEF-3 and pp31 was strongly inhibited even at the lower
      concentration of cycloheximide. Although cycloheximide was shown to be useful in
      defining early temporal classes, it induced apoptosis in both uninfected and
      infected Sf9 cells when used at the inhibitory concentration.

PMID- 9185595
TI  - Neutralization determinants of laboratory strains and field isolates of equine
      arteritis virus: identification of four neutralization sites in the amino
      terminal ectodomain of the G(L) envelope glycoprotein.
AB  - The N-terminal hydrophilic ectodomain of the G(L) envelope glycoprotein of equine
      arteritis virus (EAV) contains neutralization determinants of the virus. We
      developed a panel of 17 neutralizing murine monoclonal antibodies (MAbs) to
      further characterize the neutralization determinants of EAV. Included were 6 MAbs
      previously raised against a laboratory strain (EAVUCD) of the original Bucyrus
      strain of EAV, as well as 11 additional MAbs that were raised against a
      neutralization-resistant variant [escape mutant (EM)] virus (EM6D10) that was
      derived from EAVUCD. All MAbs raised against EAVUCD and 4 of the MAbs raised
      against EM6D10 (2B3, 5F8, 8D4, and 10B4) reacted with the corresponding G(L)
      envelope glycoprotein in a Western immunoblotting assay, whereas the remaining 7
      MAbs raised against EM6D10 did not react with any viral protein in the
      immunoblotting assay but competitively inhibited the binding of MAbs 2B3, 5F8,
      8D4, and 10B4, indicating that they also recognize epitopes on the G(L) protein.
      A panel of 18 EM viruses raised to the MAb panel, 19 field isolates of EAV from
      North America and Europe, the modified-live virus vaccine (ARVAC), and 3 other
      laboratory strains of EAV were characterized by microneutralization assay with
      the panel of neutralizing MAbs and polyclonal rabbit and horse antisera.
      Comparative analysis of the nucleotide sequences of ORF5 and the deduced amino
      acid sequences of the G(L) protein of individual EM viruses and field isolates of
      EAV identified four distinct neutralization sites. These sites include amino
      acids 49 (site A), 61 (site B), 67 through 90 (site C), and 99 through 106 (site
      D). With the notable exception of site A, the sites were all located in the V1
      variable region (amino acids 61-121) within the second half of the N-terminal
      hydrophilic ectodomain of the G(L) protein. Site D includes several overlapping
      linear epitopes which appear to interact with amino acids in the other three
      sites to form conformationally dependent epitopes. Amino acid substitutions
      within any of these four sites can alter the neutralization phenotype of
      individual strains of EAV.

PMID- 9185596
TI  - Particle bombardment-mediated DNA vaccination with rotavirus VP6 induces high
      levels of serum rotavirus IgG but fails to protect mice against challenge.
AB  - The rotavirus inner capsid protein VP6 contains conserved epitopes that are
      potential targets for eliciting protective immunity against different serotypes
      within the same group of rotavirus. In order to determine whether VP6 alone can
      induce protective immunity, an expression vector pcDNA1/EDIM6 containing gene 6
      of rotavirus EDIM strain was constructed and used as a vaccine in an adult mouse
      model. Cloned gene 6 was determined to be 1356 nucleotides long and contained a
      5' noncoding region of 23 nucleotides, a 3' noncoding region of 139 nucleotides,
      and a coding frame of 1194 nucleotides for a polypeptide of 397 amino acid
      residues. Recombinant VP6 was expressed in rabbit reticulocyte lysate and the
      heat-denatured recombinant VP6 migrated in SDS-gels with an apparent molecular
      weight of approximately 43 kDa. Five additional polypeptide bands corresponding
      to oligomers of recombinant VP6 were observed when the expressed product was not
      heat denatured. To determine the immunogenicity of recombinant VP6, female BALB/c
      mice were injected intramuscularly or intradermally with pcDNA1/EDIM6, or were
      inoculated epidermally with plasmid-coated gold beads using the Geniva Accell
      particle delivery device. Only intradermal injection and particle delivery
      elicited measurable serum anti-rotavirus IgG responses, but responses developed
      following particle delivery were significantly (P < 0.001) greater. However, none
      of the delivery methods induced serum or stool anti-rotavirus IgA responses and,
      when challenged with EDIM no protection against infection was observed in the
      immunized mice. Therefore, parenteral immunization with VP6 alone elicited large
      anti-rotavirus IgG responses but did not elicit protection against murine
      rotavirus infection in this model.

PMID- 9185597
TI  - Emergence of subtype Zaire Ebola virus in Gabon.
AB  - Gabon has recently been struck three times by Ebola hemorrhagic fever. The first
      isolate originating from the 1994 outbreak has been subjected to molecular
      characterization of its GP and VP24 genes. Sequence analysis demonstrates that
      the agent, Gabon-94 virus, belongs to subtype Zaire of Ebola virus. The isolate
      is closely related to the Kikwit-95 isolate, and both viruses seem to have
      evolved from a progenitor virus different from that of the Zaire-76 isolates. The
      relatively close relationship of all subtype Zaire viruses isolated at different
      geographical locations and up to 20 years apart suggests an extreme conservation
      in the yet unknown natural reservoir of Ebola viruses. The level of genetic
      variability in the human host might be different as indicated by the comparison
      of isolates from a single outbreak (Mayinga-76 and Eckron-76), but needs further
      investigation on clinical material of patients by PCR since both isolates have
      different levels of passages in tissue culture.

PMID- 9185598
TI  - Genome nucleotide lengths that are divisible by six are not essential but enhance
      replication of defective interfering RNAs of the paramyxovirus simian virus 5.
AB  - For some members of the Paramyxoviridae family of negative strand RNA viruses,
      efficient genome replication only occurs when the total genome length is a
      multiple of six (6N length, where N is any integer). To determine if this "rule
      of six" requirement applied to the replication of the prototype paramyxovirus
      simian virus 5 (SV5), defective interfering (DI) RNA genomes were generated by
      sequential undiluted passage of virus in tissue culture. Molecular cloning and
      nucleotide sequence analysis of 10 RNA genomes revealed a series of copyback DI
      RNAs with chain lengths between 449 and 1365 bases, but only 4 of the 10
      naturally occurring RNA genomes were of 6N length. Many of the cloned DI genomes
      could be grouped into two distinct nested sets, with the members of each set
      having the same polymerase crossover junctions and extent of terminal
      complementarity but differing from each other by internal deletions. One of these
      nested sets of genomes consisted of novel DI RNAs that contained a pentameric
      stretch of nontemplated adenosine residues inserted precisely at the polymerase
      crossover junction. A reverse genetics system was established in which SV5 DI
      genomes were replicated in vivo entirely by cDNA-derived components. Using this
      system, two naturally occurring SV5 DI RNAs were examined in a mutational
      analysis to determine the role of genome length on SV5 RNA replication. The
      progressive insertion of one to six nucleotides into a 6N length DI genome (852
      bases) resulted in a reduction in replication for RNAs that contained one to four
      additional bases (approximately 35-50% of WT levels), followed by an increase
      back to WT replication levels for genomes that were altered by five and six base
      insertions (approximately 70 and 100% of WT levels, respectively). An insertion
      of five nucleotides into a second non-6N length DI RNA (499 total bases) created
      a genome length that was a multiple of six (504 bases) and led to a approximately
      10-fold stimulation of replication over that of the unaltered genome. Together,
      these results indicate that there was a clear influence of 6N genome length on
      SV5 DI RNA replication, but the stringency of this replication requirement
      appeared to be less than that found previously for other paramyxoviruses. This
      work completes the testing of the rule of six replication requirement for
      representatives of each of the four genera of the Paramyxoviridae family and
      indicates that the preference for replication of 6N length RNA genomes varies
      between the individual paramyxoviruses.

PMID- 9185599
TI  - Protection against influenza virus encephalitis by adoptive lymphocyte transfer.
AB  - CD8+ cytotoxic T lymphocytes (CTL) have an established role in anti-viral
      immunity, but whether CTL function efficiently in the brain remains unclear. In
      particular, virus-infected neurons, which express only low levels of MHC class I
      antigens and are resistant to the induction of apoptosis, could constitute a
      relatively intractable CTL target. We have used immune lymphocytes adoptively
      transferred into the CSF to protect naive mice against an intracerebral infection
      with influenza A/WSN, a virus that infects neurons in the brain parenchyma and
      causes a lethal encephalitis. After in vitro restimulation, heterotypically
      immune spleen cells protected against A/WSN encephalitis in an H-2-restricted,
      CD8-dependent, CD4-independent manner. Adoptively transferred CTL clones were
      also protective. Homotypically immune spleen cells additionally mediated CD8
      independent, H-2-unrestricted protection, probably due to the generation of A/WSN
      specific plasma cells from memory B cells during in vitro restimulation. Thus
      after in vitro restimulation, either CTL or B cells adoptively transferred into
      the CSF protected against an acutely lethal intracerebral virus infection.

PMID- 9185601
TI  - Analysis of the two subgenomic RNA promoters for turnip crinkle virus in vivo and
      in vitro.
AB  - Infection of plants or protoplasts with turnip crinkle virus (TCV), a monopartite
      RNA virus, results in the synthesis of the genomic RNA and two subgenomic (sg)
      RNAs. The transcription start site for the 1.45-kb sgRNA was previously mapped to
      position 2606 (J. C. Carrington, T. J. Morris, P. G. Stockley, and S. C.
      Harrison, (1987). J. Mol. Biol. 194, 265-276) corresponding to position 2607 in
      the TCVms isolate and the start site for the 1.7-kb sgRNA has now been mapped to
      position 2333 in TCVms. A 96-base sequence (90 bases upstream and 6 bases
      downstream) encompassing the transcription start site for the 1.45-kb sgRNA was
      sufficient for full promoter activity. Similarly, a 94-base sequence (90 bases
      upstream and 4 bases downstream) encompassing the start site was required for
      full activity of the 1.7-kb sgRNA promoter. The 1.45-kb sgRNA promoter, but not
      the 1.7-kb sgRNA promoter, was able to direct synthesis of a nontemplate RNA in
      vitro using partially purified TCV RNA-dependent RNA polymerase. Computer
      generated secondary structures for the two sgRNA promoters revealed an extensive
      hairpin just upstream from the transcription start site. Comparisons of
      corresponding sequences from related viruses indicates higher sequence
      conservation for the 1.45-kb sgRNA promoter compared with the 1.7-kb sgRNA
      promoter, despite the latter's location within the RNA-dependent RNA polymerase
      open reading frame.

PMID- 9185600
TI  - Effects of coat protein mutations and reduced movement protein expression on
      infection spread by cowpea chlorotic mottle virus and its hybrid derivatives.
AB  - Previously we have reported that the essential 3a movement gene of icosahedral
      cowpea chlorotic mottle virus (CCMV) can be functionally replaced by the 30-kDa
      movement gene of rod-shaped sunn-hemp mosaic virus (SHMV). Because plant RNA
      viruses differ in requiring or not requiring coat protein for systemic infection,
      we have now investigated whether systemic spread by this CCMV/SHMV hybrid is
      dependent on its CCMV coat protein as well as its SHMV movement protein. We find
      that either deletion or frameshift mutations in the coat protein gene block
      systemic spread. Thus, like wild-type CCMV, systemic infection by the hybrid is
      dependent on both movement protein and coat protein. These results further
      support the conclusion that the required functions of the coat and movement
      proteins in CCMV spread do not depend on sequence-specific interaction between
      these proteins. Additional features of the hybrid also motivated testing the
      effects of modulating movement protein expression. Creating an extra, out-of
      frame translational start codon (AUG) shortly upstream of the 3a movement protein
      gene in CCMV downregulated its expression 18-fold. Nevertheless, for CCMV
      derivatives bearing either the CCMV 3a gene or the SHMV 30-kDa gene, the extra
      AUG resulted in only a minor delay in the onset of viral spread and little or no
      effect on the subsequent rate of cell-to-cell spread. Thus, under normal
      circumstances, the rate of CCMV cell-to-cell spread in cowpea plants appears to
      be limited primarily by factors other than movement protein synthesis.

PMID- 9185602
TI  - Mutations that alter a conserved element upstream of the potato virus X triple
      block and coat protein genes affect subgenomic RNA accumulation.
AB  - The putative subgenomic RNA (sgRNA) promoter regions upstream of the potato virus
      X (PVX) triple block and coat protein (CP) genes contain sequences common to
      other potexviruses. The importance of these sequences to PVX sgRNA accumulation
      was determined by inoculation of Nicotiana tabacum NT1 cell suspension
      protoplasts with transcripts derived from wild-type and modified PVX cDNA clones.
      Analyses of RNA accumulation by S1 nuclease digestion and primer extension
      indicated that a conserved octanucleotide sequence element and the spacing
      between this element and the start-site for sgRNA synthesis are critical for
      accumulation of the two major sgRNA species. The impact of mutations on CP sgRNA
      levels was also reflected in the accumulation of CP. In contrast, genomic minus-
      and plus-strand RNA accumulation were not significantly affected by mutations in
      these regions. Studies involving inoculation of tobacco plants with the modified
      transcripts suggested that the conserved octanucleotide element functions in
      sgRNA accumulation and some other aspect of the infection process.

PMID- 9185603
TI  - Phosphorylation of canine distemper virus P protein by protein kinase C-zeta and
      casein kinase II.
AB  - Transcription by nonsegmented negative-strand RNA viruses is mediated by the
      viral RNA-dependent RNA polymerase and transcriptional cofactor P. The P protein
      is activated by phosphorylation, an event initiated by cellular kinases. The
      kinase used differs among this group of RNA viruses; vesicular stomatitis virus
      and respiratory syncytial virus utilize casein kinase II (CKII), whereas human
      parainfluenza virus type 3 utilizes PKC isoform zeta (PKC-zeta) for activation of
      its P protein. To identify the cellular kinase(s) involved in the phosphorylation
      of the canine distemper virus (CDV) P protein, we used recombinant CDV P in
      phosphorylation assays with native kinase activities present in CV1 cell extracts
      or purified CKII and PKC isoforms. Here, we demonstrate that the CDV P protein is
      phosphorylated by two cellular kinases, where PKC-zeta has the major and CKII the
      minor activities. In contrast, the P protein of another member of the
      morbillivirus genus, measles virus, is phosphorylated predominantly by CKII,
      whereas PKC-zeta has only minor activity. Selective inhibition of PKC-zeta
      activity within CV1 cells eliminated permissiveness to CDV replication,
      indicating an in vivo role for PKC-zeta in the virus replication cycle. The broad
      tissue expression of PKC-zeta parallels the pantropic nature of CDV infections,
      suggesting that PKC-zeta activity is a determinant of cellular permissiveness to
      CDV replication.

PMID- 9185604
TI  - Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain
      is essential for Vpu-mediated ER degradation of CD4.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vpu is phosphorylated at two serine
      residues (Ser52 and Ser56) present within the acidic dodecapeptide region of the
      54-aa cytoplasmic domain. Previous experiments have shown that Vpu
      phosphorylation is critical for the degradation of CD4 in the endoplasmic
      reticulum. In this study, we carried out experiments to elucidate the role of
      individual phosphoacceptor sites in CD4 proteolysis. We show here that acidic
      amino acids could not functionally substitute for phosphoserines in Vpu that is
      capable of inducing the degradation of CD4. Our studies have further revealed
      that phosphorylation of either of the two phosphoacceptor sites is not sufficient
      to generate a functional Vpu protein. When tested for functional complementation,
      inactive phosphorylation-proficient Vpu mutants failed to generate Vpu proteins
      that had the ability to induce the degradation of Vpu-sensitive glycoproteins.
      The failure to complement was not due to assembly defects in the Vpu protein as
      unphosphorylated Vpu formed oligomeric complexes in the cell. We also showed that
      Vpu expression inhibits protein transport in a phosphorylation-dependent manner.
      Our studies have thus revealed that both phosphoserines in Vpu are critical
      participants in a pathway that leads to the proteolysis of CD4 in the ER and that
      these phosphoserines should be present on the same subunit of the Vpu protein.

PMID- 9185605
TI  - Oat blue dwarf marafivirus resembles the tymoviruses in sequence, genome
      organization, and expression strategy.
AB  - The complete nucleotide sequence and genome organization of oat blue dwarf
      marafivirus (OBDV) were determined. The 6509 nucleotide RNA genome encodes a
      putative 227-kDa polyprotein (p227) with sequence motifs similar to the
      methyltransferase, papain-like protease, helicase, and polymerase motifs present
      in the nonstructural proteins of other positive strand RNA viruses. The 3' end of
      the open reading frame (ORF) that encodes p227 (ORF 227) also encodes the two
      capsid proteins: a 24-kDa capsid protein is presumably cleaved from the p227
      polyprotein, whereas the 21-kDa capsid protein appears to be translated from a
      subgenomic RNA (sgRNA). Encoded amino acid and nucleotide sequence comparisons,
      as well as the OBDV genome expression strategy, show that OBDV closely resembles
      the tymoviruses. OBDV differs from the tymoviruses in its general biology, in its
      lack of a putative movement gene that overlaps the replication-associated genes,
      and in its fusion of the capsid gene sequences to the major ORF. OBDV also
      possesses a 3' poly(A) tail, as compared to the tRNA-like structures found in
      most tymoviral genomes. Due to the strong similarities in genome sequence and
      expression strategy, OBDV, and presumably the other marafiviruses, should be
      considered a member of the tymovirus lineage of the alpha-like plant viruses.

PMID- 9185607
TI  - Changes of tRNA population during compensatory cell proliferation: differential
      expression of methionine-tRNA species.
AB  - Changes of tRNA species, as both relative percentage of total tRNA and absolute
      concentration, occur during liver cell proliferation induced by partial
      hepatectomy. Transfer RNAs which are abundant under quiescence are found to
      decrease during hepatocyte proliferation, and vice versa. One consequence of
      these changes is the differential expression of methionine-isoaccepting tRNA
      species. Initiator tRNA(Met) is present in scarce amounts under quiescent
      conditions and increases during cell-cycle progression. Elongator tRNA(Met) shows
      the opposite behavior. Both the quantitative and qualitative tRNA changes return
      to control levels as the liver returns to resting conditions. These changes might
      have mechanistic implications in modulating the protein synthesis required by
      cell proliferation. Moreover, the increase of initiator tRNA(Met) species might
      be necessary to translate protooncogene, growth factor, and receptor mRNAs, the
      translation of which is hindered by inhibitory AUG triplets upstream from the
      coding sequence. Thus the tRNA changes described herein could be involved in
      regulating translation of transcripts encoding cell-cycle associated proteins.

PMID- 9185606
TI  - Synthesis and processing of the equine herpesvirus 1 glycoprotein M.
AB  - In a previous report, the function of the equine herpesvirus 1 (EHV-1)
      glycoprotein M (gM) homolog was investigated. It was shown that EHV-1 gM is
      involved in both virus entry and direct cell-to-cell spread of infection (N.
      Osterrieder et al., J. Virol. 70, 4110-4115, 1996). In this study, experiments
      were conducted to analyze the synthesis, posttranslational processing, and the
      putative ion channel function of EHV-1 gM. It was demonstrated that EHV-1 gM is
      synthesized as an Mr 44,000 polypeptide, which is cotranslationally N
      glycosylated to an Mr 46,000-48,000 glycoprotein. The Mr 46,000-48,000 gM moiety
      is processed to an Mr 50,000-55,000 glycoprotein, which is resistant to treatment
      with endoglycosidase H, indicating that processing occurs in the Golgi network.
      EHV-1 gM forms a dimer in infected cells and the virion, as was demonstrated by
      the presence of an Mr 105,000-110,000 gM-containing band in electrophoretically
      separated lysates of infected cells and purified extracellular virions. The Mr
      105,000-110,000 protein band containing gM was also observed in lysates of cells
      that had been transfected with EHV-1 gM DNA. The translation of EHV-1 gM is
      initiated at the first in-frame methionine of the gM open reading frame as shown
      by transient transfection experiments of full-length gM and a truncated gM
      lacking the aminoterminal 83 amino acids. Functional expression of EHV-1 gM in
      Xenopus laevis oocytes together with voltage-clamp analyses demonstrated that gM
      per se does not exhibit ion channel activity as had been speculated from the
      predicted structure of the polypeptide.

PMID- 9185608
TI  - Hamster adapt78 mRNA is a Down syndrome critical region homologue that is
      inducible by oxidative stress.
AB  - We are using the technique of mRNA differential display to identify RNAs that may
      be important in protecting cells against the damaging effects of oxidative
      stress. For these studies, we utilize a so-called "adaptive response" model
      system in which hamster HA-1 cells respond to a minimally toxic "pretreatment"
      dose of hydrogen peroxide by synthesizing RNAs and proteins that protect them
      against subsequent exposure to a highly cytotoxic concentration of hydrogen
      peroxide. Using this approach, we have recently reported several novel RNAs whose
      levels are increased under conditions of adaptive response. Here we report a new
      RNA, designated adapt78, whose steady-state level is significantly induced by a
      pretreatment dose of hydrogen peroxide. adapt78 mRNA was calculated to be 2.35 kb
      in size and inducible by the standard pretreatment dose of 4 micromol H2O2/10(7)
      cells. It was induced as early as 90 min after peroxide exposure and maximally at
      5 h. Induction was strongly dependent upon calcium. Cloning and sequencing
      revealed a large predicted open reading frame of 197 amino acids. In vitro
      transcription and translation generated a protein of 25,000 Da. GenBank homology
      analysis revealed that much of adapt78 is strongly homologous to a sequence that
      has been mapped to the Down syndrome critical region (Fuentes et al., Hum. Mol.
      Genet. 4, 1935-1944, 1995). However, both the 5' and the 3' ends of adapt78 show
      no homology to any previously reported complete sequence. adapt78 represents a
      new oxidant-inducible RNA and marker of cellular oxidative stress and may provide
      new insight into our understanding of oxidant-related disorders and neural
      degeneration.

PMID- 9185609
TI  - Nitric oxide synergistically enhances DNA strand breakage induced by
      polyhydroxyaromatic compounds, but inhibits that induced by the Fenton reaction.
AB  - Reactive oxygen and nitrogen species play an important role in many human
      diseases including cancer. We have found that incubation of pBR322 plasmid DNA
      with a nitric oxide (NO)-releasing compound such as diethylamine NONOate and a
      polyhydroxyaromatic compound such as catechol, 1,4-hydroquinone, or pyrogallol
      caused synergistic induction of single-strand breakage, whereas either compound
      alone induced much less breakage. Phenol, resorcinol, or guaiacol (O
      methylcatechol) did not exhibit this synergistic effect of DNA damage with NO.
      The strand breakage induced by NO with pyrogallol was prevented by excess
      superoxide dismutase, carboxy-PTIO (an NO-trapping agent), or anti-oxidants
      (urate, ascorbate). Possible mechanisms for the induction of this synergistic
      effect of NO and polyhydroxyaromatic compounds on the strand breakage are
      proposed, including involvement of peroxynitrite formed from NO and O2.- derived
      from autooxidation of polyhydroxyaromatics. This pathway for generation of
      reactive species from NO and catechol-type compounds (e.g., L-dopa, catechol
      estrogen) may be important in many pathological conditions, because both
      compounds are concurrently formed or present in vivo. On the other hand, NO dose
      dependently inhibited the strand breakage mediated by 1,4-hydroquinone plus Cu2+
      or Fenton reaction (H2O2, iron or copper). This inhibition could be due to
      formation of a complex between NO and a metal ion, inhibiting generation of
      reactive species from H2O2. Our results can account for contrasting activities of
      NO reported in relation to tissue injury. NO can play both detrimental and
      beneficial roles in DNA damage, depending on the type and amounts of reactive
      oxygen species and metal ions concurrently present.

PMID- 9185610
TI  - Influence of the redox state of pyridine nucleotides on mitochondrial sulfhydryl
      groups and permeability transition.
AB  - This work addresses a correlation between the redox state of pyridine nucleotides
      and that of sulfhydryl groups of the mitochondrial membranes. Several major
      observations emerge: (1) Conditions leading to an oxidation of the pyridine
      nucleotides such as incubation with tert-butyl hydroperoxide or acetoacetate
      determine a decrease of total mitochondrial sulfhydryl groups. Glutathione does
      not follow the same pattern since it decreases in the presence of tert-butyl
      hydroperoxide but not in the presence of acetoacetate. In addition, only in the
      presence of tert-butyl hydroperoxide is the decrease of sulfhydryl groups
      concomitant with a membrane protein polymerization, observed by polyacrylamide
      gel electrophoresis. (2) Under all conditions tested, the oxidation of sulfhydryl
      groups is further stimulated by the presence of calcium and phosphate ions. (3)
      Respiratory substrates, which prevent the swelling of mitochondria, also
      partially prevent the decrease of sulfhydryl groups.

PMID- 9185611
TI  - Aberrant O-glycosylation in the collagenous domain of pro alpha2(I) procollagen
      subunits synthesized by chemically transformed hamster fibroblasts.
AB  - Chemically transformed Syrian hamster embryo fibroblasts (NQT-SHE) do not
      synthesize the pro alpha1(I) subunit of type I collagen, but they secrete two
      forms of the pro alpha2(I) subunit (N33 and N50) with abnormal post-translational
      modifications localized in the alpha2CB3,5 cyanogen bromide peptide of the
      collagenous domain (B. Peterkofsky and W. Prather (1992) J. Biol. Chem. 267 5388
      5395). Isoelectric focusing and treatment of the modified chains with
      glycosidases and biotinylated Jacalin lectin identified the modifications as Gal
      beta1,3-GalNAc-O-Ser/Thr with or without a terminal sialic acid in an alpha2,6
      linkage. Unhydroxylated N33 alpha-chains also reacted with Jacalin, confirming
      that the abnormal modification was O-glycosylation and not hyperhydroxylation of
      proline or lysine. Cells were treated with benzyl GalNAc, a competitive inhibitor
      of galactosyl transferase that prevents addition of Gal to GalNAc-O-Ser/Thr and
      thus blocks elongation of O-glycosyl chains. Treated cells secreted pro alpha2(I)
      chains containing GalNAc-O-Ser/Thr but no galactose or sialic acid, which
      suggested that Gal addition takes place before sialylation. Treatment of NQT-SHE
      cells with monensin and brefeldin A inhibited secretion and led to intracellular
      accumulation of pro alpha2(I) chains that contained only GalNAc. Therefore, it
      appears that GalNAc addition to pro alpha2(I) chains in NQT-SHE cells occurs in
      the cis-Golgi, while sialic acid and galactose are added in the trans-Golgi
      network. The pro alpha2(I) chains produced by NQT-SHE cells most likely are
      modified because they are in the denatured state, and thus potential O
      glycosylation sites become available that would not be exposed in normal triple
      helical procollagen.

PMID- 9185612
TI  - A 33.5-kDa heat- and protease-resistant NADH oxidase inhibited by capsaicin from
      sera of cancer patients.
AB  - Sera from patients with a variety of cancers, including solid carcinomas,
      leukemias, and lymphomas, contain a ca. 33.5-kDa protein absent from sera of
      healthy volunteers or patients not diagnosed as having cancer. The protein
      exhibits an NADH oxidase activity inhibited by 8-methyl-N-vanillyl-6-noneamide
      (capsaicin). The activity and the protein are resistant to digestion by proteases
      (trypsin, chymotrypsin, proteinase K, subtilisin) and to heat. Following protease
      digestion to reduce the content of major serum proteins, the 33.5-kDa protein
      could be detected on Western blots of SDS-PAGE transferred to nitrocellulose
      membranes using polyclonal antisera to a corresponding partially purified 33.5
      kDa protein shed into culture media conditioned by growth of HeLa cells. No
      corresponding protein was seen with control sera. The findings confirm the
      capsaicin-inhibited NADH oxidase activity of cancer sera as a circulating marker
      potentially specific to sera of cancer patients and identify a ca. 33.5-kDa
      protein resistant to proteases and heat as the source of the circulating
      capsaicin-inhibited NADH oxidase activity.

PMID- 9185613
TI  - Generation and characterization of mouse monoclonal antibodies specific for N
      linked neutral oligosaccharides of glycoproteins.
AB  - We generated four monoclonal antibodies (MAbs) specific for asparagine-linked
      neutral oligosaccharides of glycoproteins by immunizing mice with neoglycolipids,
      which were derived from glycoproteins by conjugation to phosphatidylethanolamine
      dipalmitoyl. The binding specificity of these MAbs was determined by an enzyme
      linked immunosorbent assay and immunostaining on thin-layer chromatography. The
      four MAbs designated OMB3, OMB4, OMR5, and OMR6 reacted strongly with the
      neoglycolipids, Gal beta1-4GlcNAc beta1-2Man alpha1-6(Gal beta1-4GlcNAc beta1
      2Man alpha1-3)Man beta1-4GlcNAc-PD, GlcNAc beta1-2Man alpha1-6(GlcNAc beta1-2Man
      alpha1-3)(GlcNAc beta1-4)Man beta1-4GlcNAc beta1-4GlcNAc-PD, Man alpha1-6Man
      beta1-4GlcNAc beta1-4(Fuc alpha1-6)GlcNAc-PD, and Man alpha1-3Man beta1-4GlcNAc
      PD, respectively, that were used as immunogens. All of these MAbs exhibited a
      high binding specificity. The epitopes of the MAbs OMB3 and OMB4 were suggested
      to be nonreducing terminal trisaccharides, Gal beta1-4GlcNAc beta1-2Man-, and
      nonreducing beta-GlcNAc residues, respectively. MAbs OMR5 and OMR6 showed a
      highly restricted binding specificity, reacting only with the immunizing
      neoglycolipids. Subsequently, MAbs OMB3 and OMB4 were shown to react strongly
      with asialo-alpha1-acid-glycoprotein and asialo-agalacto-alpha1-acid
      glycoprotein, respectively, by Western blotting. Furthermore, it was shown that
      these MAbs reacted specifically with the epitope on Chinese hamster ovary cells
      by an immunofluorescence technique. MAb OMB4 was also shown to detect the
      accumulated oligosaccharides with nonreducing terminal beta-GlcNAc residues as
      granular inclusions in the cultured fibroblasts from a classical Sandhoff disease
      patient.

PMID- 9185614
TI  - Activity, peroxide compound formation, and heme d synthesis in Escherichia coli
      HPII catalase.
AB  - Wild-type Escherichia coli HPII catalase (heme d containing) has 15% the activity
      of beef liver enzyme per heme. The rate constant for compound I formation with
      H2O2 is 1.3 x 10(6) M(-1) s(-1). HPII compound I reacts with H2O2 to form O2 with
      a rate constant of 1.8 x 10(6) M(-1) s(-1). Forty percent of HPII hemes are in
      the compound I state during turnover. Compound I is reduced by ethanol and
      formate at rates of 5 and 13 M(-1) s(-1) (pH 7.0), respectively. Incubation of
      HPII compound I with ferrocyanide and ascorbate does not form a compound II
      species. Mutation of His128 to alanine or asparagine gives inactive protoheme
      proteins. Mutation of Asn201 gives partially active heme d forms. Asn201Ala has
      24%, Asn201Asp 10%, and Asn201Gln 0.4% of wild-type activity. Asn201His contains
      protoheme when isolated and converts this via protoheme compound I to a heme d
      species. Both distal heme cavity residues His128 and Asn201 are implicated in
      catalytic activity, compound I formation, and in situ heme d biosynthesis. HPII
      Asn201, like the corresponding residue in protoheme catalases, may promote H+
      transfer to His128 imidazole, facilitating (i) peroxide anion binding to heme and
      (ii) stabilization of a transition state for heterolytic cleavage of the O-O
      bond.

PMID- 9185615
TI  - Substrate-based inhibitors of the (S)-adenosyl-L-methionine:delta24(25)- to
      delta24(28)-sterol methyl transferase from Saccharomyces cerevisiae.
AB  - A series of 31 side-chain-modified analogs of cholesterol, zymosterol,
      lanosterol, and cycloartenol and the steroidal alkaloids solasodine and
      solanidine were studied as inhibitors of (S)-adenosyl-L-methionine:delta24(25)
      sterol methyl transferase (SMT) enzyme activity from Saccharomyces cerevisiae.
      Two classes of sterol methylation inhibitors were tested: substrate analogs,
      including mechanism-based inhibitors, and transition state analogs. Several novel
      sterol methylation inhibitors that contained an aza, aziridine, or ammonium group
      in the sterol side chain were prepared and tested for the first time. The degree
      and kinetic pattern of methylation inhibition were found to be influenced by the
      position and nature of the variant functional group introduced into the side
      chain. The most potent inhibitors of SMT enzyme activity were transition state
      analog inhibitors (Ki values of 5 to 10 nM) that mimicked the structure and
      conformation of the natural substrate presumed to form in the ternary complex
      generated in the transition state. Steroidal alkaloids were potent competitive
      inhibitors with Ki values ranging from 2 to 30 microM, which is about the Kmapp
      of zymosterol, ca. 27 microM. An isosteric analog of the natural substrate,
      zymosterol, in which the 26/27-gem-dimethyl groups were joined to form a
      cyclopropylidene function is shown to be a potent irreversible mechanism-based
      inactivator of SMT enzyme activity that exhibits competitive-type inhibition, Ki
      48 microM with a K(inact) of 1.52 min(-1). Mechanistic implications of these
      results provide new insights into the topology of the ternary complex involving
      sterol-AdoMet-enzyme.

PMID- 9185617
TI  - Comparing the properties of Escherichia coli branching enzyme and maize branching
      enzyme.
AB  - Escherichia coli glycogen branching enzyme (GBE) and maize starch branching
      enzymes I (SBEI) and II (SBEII) were expressed in E. coli and purified. E. coli
      GBE branched amylose at a higher rate than did SBEII, but branched amylose at a
      lower rate than did SBEI. Similar to SBEI, GBE branched amylopectin at a lower
      rate than did SBEII. High-performance anion-exchange chromatography analysis of
      the branched products produced by BE revealed the minimum chain length (cl)
      required for branching. While GBE and SBEII showed the same minimum cl [degree of
      polymerization (dp) 12] required for branching, SBEI had a slightly higher
      minimum cl (dp 16) requirement for branching. The major differences between GBE
      and SBE are their specificities in terms of the size of chains transferred. In
      comparison with SBE, GBE had a much narrower size range of chains transferred and
      transferred mainly shorter chains. While SBEI and SBEII produced a large number
      of chains ranging from dp 6 to over dp 30, GBE predominantly transferred chains
      ranging from dp 5 to 16 and produced only a very small number of long chains with
      dp greater than 20. Although it has been reported that SBEI and SBEII
      preferentially transfer longer and shorter chains, respectively (1), this study
      further defines the differences between SBEI and SBEII in the size of chains
      transferred. SBEI predominantly transfers longer chains with dp greater than 10,
      while producing few shorter chains with dp 3 to 5. In contrast, SBEII
      preferentially transfers smaller chains with dp 3 to 9, with the most abundant
      chains being dp 6 and 7. The significance of minimum chain-length requirement by
      SBE is discussed in setting the invariant size of amylopectin cluster size (9
      nm).

PMID- 9185616
TI  - Competitive interactions between cytochromes P450 2A6 and 2E1 for NADPH
      cytochrome P450 oxidoreductase in the microsomal membranes produced by a
      baculovirus expression system.
AB  - The present study investigated the interactions between cytochrome P450 (P450)
      enzymes and the NADPH:cytochrome oxidoreductase (OR) in the microsomal membrane.
      Microsomes containing human cytochrome P450 2A6 (h2A6) coexpressed with human OR
      (hOR) via a baculovirus expression system displayed coumarin hydroxylase activity
      with apparent Km and Vmax values of 0.41 microM and 4.05 nmol/min/nmol P450,
      respectively. Incorporation of purified rat liver cytochrome b5 (b5) into the
      microsomes increased the Vmax 2.5-fold, but did not affect the Km. The N
      nitrosodimethylamine (NDMA) demethylase activity of human cytochrome P450 2E1
      (h2E1) coexpressed similarly was characterized previously. Coumarin was shown not
      to be a substrate nor an inhibitor of h2E1, and NDMA was not a substrate nor an
      inhibitor of h2A6. In microsomes containing h2A6, h2E1, and hOR (M-h2A6-h2E1-hOR)
      obtained from a triple expression system, the two P450 enzymes were shown to
      compete with each other for interaction with hOR. In incubations with M-h2A6-h2E1
      hOR, the presence of a h2A6 substrate (coumarin) decreased NDMA demethylase
      activity by a maximum of 47%, and the presence of a h2E1 substrate (NDMA)
      decreased coumarin hydroxylase activity by a maximum of 19%. This substrate
      induced competition between h2A6 and h2E1 was decreased by the addition of
      purified b5. In the absence of a substrate, the NADPH-dependent H2O2 formation
      was high in both M-h2A6-h2E1-hOR and M-h2E1-hOR, but low in M-h2A6-hOR. The
      addition of NDMA had little effect on the H2O2 formation in M-h2A6-h2E1-hOR and M
      h2E1-hOR. The addition of coumarin, however, slightly decreased H2O2 formation in
      M-h2A6-h2E1-hOR, but drastically increased H2O2 formation in M-h2A6-hOR. These
      results suggest that the presence of a h2A6 substrate decreased the electron flow
      to h2E1 in M-h2A6-h2E1-hOR. The activities of coumarin hydroxylase and NDMA
      demethylase of M-h2A6-h2E1-hOR were decreased and increased, respectively, by an
      increase in ionic strength. The ionic strength, however, did not drastically
      change the substrate-induced competition between h2A6 and h2E1 for hOR. The
      results demonstrate the usefulness of the coexpression system for mechanistic
      studies and illustrate that the interaction of monooxygenase enzymes in the
      microsomal membrane is regulated by the presence of substrates and b5.

PMID- 9185618
TI  - Muscle-specific calpain, p94, interacts with the extreme C-terminal region of
      connectin, a unique region flanked by two immunoglobulin C2 motifs.
AB  - Using the yeast two-hybrid system, we have recently reported that skeletal muscle
      specific calpain, p94, binds specifically to connectin (or titin), a gigantic
      muscle elastic protein. Connectin has at least two binding sites for p94; one is
      at the N2-line region and the other is at the extreme C-terminus. In order to
      analyze the interaction between p94 and the C-terminus of connectin, we examined
      the C-terminal sequence of human skeletal muscle connectin. The sequence was
      essentially identical to that of heart muscle reported by Labeit and Kolmerer
      (1995, Science 270, 293-296), and the minimal binding site for p94 contained two
      IgC2 motifs and the intervening sequence called "M-is7." The exon encoding M-is7
      is reported to be alternatively spliced depending on muscle tissues, resulting in
      the existence of both types of connectin with and without M-is7. However, the C
      terminal region of connectin bound to p94 through M-is7. Our results suggest that
      the interaction between p94 and the C-terminus of skeletal muscle-type connectin
      is involved in tissue-specific myofibriogenesis.

PMID- 9185619
TI  - Elucidating mechanisms of thermostabilization of poliovirus by D2O and MgCl2.
AB  - To understand a significant reduction in the loss of poliovirus infectivity by
      D2O and a combination of D2O and MgCl2 at 37-45 degrees C, this paper attempts to
      elucidate the mechanisms underlying the thermostabilization of poliovirus. Three
      serotypes of Sabin oral poliovirus vaccine strains were investigated. Temperature
      dependent fluorescence emission intensity studies showed that the effects of D2O
      and MgCl2 on the stability and conformation of poliovirus are correlated with
      those of the infectivity of poliovirus. Fluorescence steady-state polarization
      revealed that the conformation of poliovirus capsid is sensitive to D2O medium
      and MgCl2 salt, and that the rigidity of poliovirus conformation is increased in
      their presence. The exposure of poliovirus tryptophan residues to water is
      modified by D2O and MgCl2, as evidenced by changes in fluorescence emission
      intensity excited at 295 nm. The involvement of hydrogen bonding in the D2O
      effect was demonstrated by the greatly increased value of relative fluorescence
      intensity. Conformational alteration was also shown by changes in the positive
      band (193-230 nm) of circular dichroism spectra. D2O and MgCl2 were also found to
      reduce the interaction of virus with water as examined by differential scanning
      microcalorimetry, leading to a decline in the extent of water penetration into
      the poliovirus capsid. All these observations were found to be more profound in a
      combination of D2O with MgCl2 than D2O or MgCl2 alone. By inducing a conformation
      favorable to maintaining the poliovirus assembly and by reducing virus-water
      interaction to decrease water penetration into the poliovirus capsid, D2O, MgCl2,
      or D2O-MgCl2 is able to exert its thermostabilization effect. Thus, to maintain
      the virus assembly and conformation of the virus and to reduce the swelling of
      the virus capsid are key factors in increasing the thermostability of poliovirus.
      These two factors are mutually complementary. The latter can provide a favorable
      environment for the formers and the formers, in turn, lead to the latter.

PMID- 9185620
TI  - Interaction between the SH2 domains of ZAP-70 and the tyrosine-based activation
      motif 1 sequence of the zeta subunit of the T-cell receptor.
AB  - One of the key steps involved in T-cell activation is binding of the tyrosine
      kinase ZAP-70 via its two SH2 domains to peptide segments termed tyrosine-based
      activation motifs (ITAM) which are present in three of the T-cell receptor (TCR)
      subunits. The crystal structure of the ZAP-70 SH2 domains complexed to
      phosphopeptide revealed that the amino-terminal phosphotyrosine-binding pocket is
      formed at the interface between the two SH2 domains. This study was designed to
      further characterize the binding between TCR zeta ITAM1 and the ZAP-70 SH2
      domains as well as to assess the change in conformation of SH2 domain structure
      upon zeta ITAM1 binding. BIAcore analysis of wild type and nonfunctional single
      point mutants of ZAP-70 SH2 domains demonstrated that the amino-terminal SH2
      domain can bind phosphopeptide in the absence of a functional carboxyl-terminal
      SH2 domain. In addition, the amino-terminal SH2 domain prefers the RREEpYDVLDK
      sequence of zeta chain ITAM1 over the GQNQLpYNELNL sequence. To assess changes in
      protein conformation upon ITAM binding to ZAP-70 SH2 domains, fluorescence
      spectroscopy and analytical ultracentrifugation experiments were performed. A
      significant blue shift in the tryptophan emission spectrum of the SH2 domains was
      observed in the presence of saturating amounts of phosphopeptide, indicating a
      loss in solvent exposure for the tryptophan residues in the protein
      phosphopeptide complex. This was accompanied by changes in the frictional
      coefficient consistent with a compacting of the protein structure. Finally,
      thermal denaturation experiments showed an increase in stability and
      cooperativity in unfolding for the protein-phosphopeptide complex relative to the
      protein alone.

PMID- 9185621
TI  - Increased transcription of the regulatory subunit of gamma-glutamylcysteine
      synthetase in rat lung epithelial L2 cells exposed to oxidative stress or
      glutathione depletion.
AB  - gamma-Glutamylcysteine synthetase (GCS) is the initial and rate-limiting enzyme
      in the glutathione (GSH) de novo synthesis pathway. GCS is composed of a heavy
      (73-kDa) catalytic subunit and a light (30-kDa) regulatory subunit, which
      maintains the Km for glutamate near physiologic concentrations. Previous studies
      have shown that the steady-state mRNA level and gene transcription for the
      catalytic subunit increased in response to the redox-cycling quinone 2,3
      dimethoxy-1,4-naphthoquinone (DMNQ) in rat lung epithelial L2 cells (M. M. Shi,
      et al., 1994, J. Biol. Chem. 269,26512-26517). The ratio of the catalytic to
      regulatory subunit mRNAs varies among tissues, and the anticancer drug cisplatin
      appears to induce only the catalytic subunit, suggesting independent gene
      regulation of the two subunits. Nonetheless, the present study found that the
      steady-state mRNA level and the transcription rate of the GCS regulatory subunit
      also increased under DMNQ-induced oxidative stress. Changes in mRNA followed a
      pattern similar to that for the catalytic subunit. The mRNA levels of the two
      subunits of GCS also both increased above the baseline levels in cells treated
      with BSO, an inhibitor of GCS enzymatic activity. These data suggest that, under
      conditions of oxidative stress or glutathione depletion, the regulatory subunit
      is upregulated at the level of mRNA transcription. Along with the elevation of
      the catalytic subunit, this increase in GCS regulatory subunit transcription
      contributes to increases in GCS enzymatic activity and cellular GSH content.

PMID- 9185622
TI  - Characterization of a pretranscriptional pathway for induction by phenobarbital
      of cytochrome P450 3A23 in primary cultures of adult rat hepatocytes.
AB  - Our laboratory has proposed that phenobarbital (PB), a typical lipophilic agent
      that induces some members of the supergene family of liver microsomal cytochromes
      P450 (e.g., CYP2B1/2 and CYP3A23), acts through a complex process inhibitable by
      the presence of growth hormone (GH), the absence of some components of the
      extracellular matrix, or a disrupted cytoskeleton. To verify that these
      manipulations of the culture environment block specific steps in the PB induction
      pathway rather than simply exerting nonspecific or toxic effects on CYP2B1/2 gene
      transcription, we have now examined PB induction of CYP3A23, a gene known to also
      be transcriptionally activated by dexamethasone (DEX) through a "nonclassical"
      pathway apparently involving the glucocorticoid receptor. We found that in
      primary cultures of adult rat hepatocytes treated with PB, induction of CYP3A23
      mRNA, just as we reported for induction of CYP2B1/2 mRNA, required the use of
      Matrigel (a reconstituted basement membrane) and was blocked by the presence of
      cytoskeletal inhibitors (colchicine or cytochalasins) or of physiologic
      concentrations of GH in the culture medium. Moreover, PB induction of CYP3A23 and
      of CYP2B1/2 mRNAs was greatly diminished by inhibitors of cAMP-dependent protein
      kinase (PKA). In striking contrast, induction of CYP3A23 mRNA by DEX was
      unaffected by any of these alterations of the culture conditions that block its
      induction by PB. We conclude that the effects of extracellular matrix, GH,
      disruption of the cytoskeleton, and activation of cAMP-dependent protein kinase,
      pharmacologically define multiple, pretranscriptional steps in the pathway(s) for
      PB induction of liver cytochromes P450.

PMID- 9185623
TI  - Effect of butylhydroxytoluene and related compounds on permeability of the inner
      mitochondrial membrane.
AB  - Mitochondrial inner membrane contains a latent pore (PTP) that when opened
      uncouples mitochondrial energy transduction and allows rapid equilibration of low
      molecular-weight solutes between the matrix and exterior. Based on sensitivity of
      the PTP to well-known free radical scavenger butylhydroxytoluene (BHT), it has
      been proposed that increased steady-state level of oxygen radicals, and
      subsequent radical attack of proteins and lipids, is a central event in
      activation of this pore (Novgorodov et al., J. Bioenerg. Biomembr. 19, 191-202,
      1987; Carbonera and Azzone, Biochim. Biophys. Acta 943, 245-255, 1988). Present
      studies revealed that DBT, a derivative of BHT devoid of radical scavenging
      activity, exerts an analogous effect on the permeability of the inner membrane.
      Inhibition of the Ca2+-induced PTP opening is essentially complete at dose range
      of 50-60 nmol/mg protein with IC50 values of about 32 and 23 nmol/mg protein for
      DBT and BHT, respectively. Electron microscopy and osmotic experiments utilizing
      polyethylene glycols with different Stokes radii showed that the apparent lack of
      inhibition seen at high concentrations of these compounds results from
      cyclosporin A- and Ca2+-insensitive pore formation in the inner membrane.
      Experiments employing antioxidants with similar structure but dissimilar
      hydrophobicity provided evidence for localization of the antioxidant binding
      sites within the hydrophobic zone of the inner membrane or in the matrix space.
      The data obtained do not refute the notion that oxygen radicals modulate the PTP,
      but rather indicate that BHT operates independently of its free radical
      scavenging activity. Overall, the sensitivity to BHT and other antioxidants is
      not always a reliable criterion for the involvement of free radical reactions in
      the processes under study.

PMID- 9185624
TI  - Effect of caffeic acid dietary supplementation on the antioxidant defense system
      in rat: an in vivo study.
AB  - Dietary supplementation of caffeic acid (0.2 and 0.8% w/w) in rats resulted in a
      statistically significant increase of alpha-tocopherol both in plasma and
      lipoprotein. While caffeic acid was not detectable in plasma under fasting
      conditions, in postprandial plasma it was present at micromole concentrations,
      doubling plasma total antioxidant capacity. Lipoproteins from caffeic acid-fed
      rats were more resistant than control to Cu2+-catalyzed oxidation, despite the
      lack of incorporation of caffeic acid in the particles. No significant effects on
      plasma and liver copper concentration, nor the increase in liver of Mn-superoxide
      dismutase reported in copper deficiency, were detected. These results demonstrate
      the physiological relevance of caffeic acid and its antioxidant action in vivo,
      through both a direct contribution to the antioxidant defense system and a
      sparing effect on alpha-tocopherol.

PMID- 9185625
TI  - Identification of chiro-inositol and its formation by isomerization of myo
      inositol during hydrolysis of glycosylphosphatidylinositol-anchored proteins.
AB  - myo-Inositol has been believed to be a sole inositol isomer existing in
      phosphatidylinositol (PI) and related derivatives. In this experiment, chiro
      inositol, an inositol isomer other than myo-inositol, was identified in
      hydrolytic products from several GPI-anchored proteins. The chiro-inositol
      contents in several different GPI-anchored proteins including 5'-nucleotidase of
      bovine liver and alkaline phosphatase of mouse NS-1 varied with hydrolytic
      conditions of these GPI anchor. Isomerization of 20-60% of myo-inositol occurred
      on the hydrolysis in 6 N HCl solution. Under the hydrolytic conditions of a HCl
      gas stream in place of solution, however, isomerization was very low (less than
      0.1%). Even in the hydrolysis under HCl gas stream, existence of CNBr accelerated
      the isomerization of inositol in GPI up to 70-95%. In the hydrolysis of
      phosphatidylinositol or myo-inositol 1-phosphate, however, a significant amount
      of chiro-inositol was not detected in 6 N HCl solution or in the existence of
      CNBr under the HCl stream. These facts indicated that isomerization occurred
      during the hydrolysis of the GPI anchor, when myo-inositol is substituted by
      glucosamine at 6-OH and is substituted by phosphate at 1-OH. It also suggested
      that the former identification of chiro-inositol in GPI structure in the various
      reports might be due to isomerization.

PMID- 9185626
TI  - Kinetics of calcium release from manganese peroxidase during thermal
      inactivation.
AB  - It was previously reported that manganese peroxidase from the white-rot fungus
      Phanerochaete chrysosporium was susceptible to thermal inactivation because it
      contains relatively labile Ca2+ ions required for stability and activity
      [Sutherland and Aust (1996) Arch. Biochem. Biophys. 332, 128-134]. In this work
      we determined that four Ca2+ ions are present in the enzyme as isolated but this
      was reduced to 2 mol/mol upon treatment with Ca2+-chelating agents or extensive
      dialysis of dilute enzyme. One of two relatively tightly bound Ca2+ remaining in
      the enzyme was released during thermal inactivation at pH 7.2. Inactive enzyme
      contained one Ca2+ which could be removed in acidic conditions. Inactivation
      kinetics were biphasic and the rates for the two inactivation steps and the
      release of Ca2+ during inactivation suggested that the first, faster phase of
      inactivation was coupled to the removal of Ca2+. The weakly associated Ca2+
      normally present in the enzyme did not affect enzyme activity and did not seem to
      protect the enzyme from thermal inactivation at submicromolar enzyme
      concentrations. Excess Ca2+ or Mn2+ decreased the rate of the thermal
      inactivation and Mn2+ stabilized the enzyme more efficiently than Ca2+ at higher
      temperature. Enzyme stabilization by Mn2+ was proposed to be due to binding of
      Mn2+ to the Mn2+ substrate binding site. In competition studies, Ca2+ was shown
      to bind to this site with apparent dissociation constants of 10(-2) and 10(-4) M
      at pH 4.5 and 7.2, respectively. Moreover, Ca2+ was a poor inhibitor of manganese
      peroxidase activity at pH 4.5. It is therefore suggested that Ca2+ is absent from
      the substrate site in physiological conditions but can bind to this site at
      higher pH and therefore may stabilize the enzyme by binding to both the Mn2+ site
      and, as previously proposed, to the distal Ca2+ site.

PMID- 9185627
TI  - Folate utilization by monomeric versus heterotetrameric sarcosine oxidases.
AB  - There are two types of bacterial sarcosine oxidases. The heterotetrameric enzymes
      contain subunits ranging in size from about 10 to 100 kDa, noncovalently bound
      FAD and NAD+, and covalently bound FMN attached to the beta subunit (42-45 kDa).
      Monomeric sarcosine oxidases are similar in size to the beta subunit in the
      heterotetramers and contain covalently bound FAD. Formaldehyde formation during
      sarcosine oxidation by several heterotetrameric sarcosine oxidases was suppressed
      in the presence of 50 microM [6S]-tetrahydrofolate, accompanied by a 25-50%
      increase in the rate of sarcosine oxidation. In contrast, [6S]-tetrahydrofolate
      caused only a modest decrease in the rate of formaldehyde production with
      monomeric sarcosine oxidases (approximately 25%), an effect which was virtually
      entirely attributable to an accompanying decrease in the rate of sarcosine
      oxidation. In the presence of 100 microM [6R,S]-tetrahydropteroyltriglutamate
      [H4Pte(Glu)3], the heterotetrameric enzymes catalyzed the formation of 5,10
      methylenetetrahydropteroyltriglutamate [5,10-CH2-H4Pte(Glu)3] at a rate which was
      35-60% faster than the rate of sarcosine oxidation in the absence of folate. An
      apparent Km value of 3.1 microM was estimated for [6S]-H4Pte(Glu)3 with the
      heterotetrameric corynebacterial sarcosine oxidase. In contrast, slow formation
      of 5,10-CH2-H4Pte(glu)3 was detected during sarcosine oxidation with monomeric
      sarcosine oxidases, attributable to the nonenzymatic reaction of free
      formaldehyde with H4Pte(Glu)3. The results show that only the heterotetrameric
      sarcosine oxidases can use tetrahydrofolates as substrates and, in this regard,
      they resemble mammalian sarcosine and dimethylglycine dehydrogenases.

PMID- 9185628
TI  - Carbonyl cyanide phenylhydrazones as probes of the anionic activator site of the
      human erythrocyte glutathione adduct transport ATPase.
AB  - We have previously shown that the ATPase activity associated with the erythrocyte
      glutathione adduct transporter is also stimulated by 2,4-dinitrophenol and p
      trifluoromethoxy carbonylcyanide phenylhydrazone, both well-known anionic and
      lipophilic uncouplers of oxidative phosphorylation by mitochondria [C. G. Winter,
      D. C. DeLuca, and H. Szumilo (1994) Arch. Biochem. Biophys. 314, 17-22]. In this
      paper, we report the testing of a series of ring-substituted carbonylcyanide
      phenylhydrazones as activators of the ATPase. All of the compounds tested
      stimulated the ATPase to similar extents, based on Vmax values. The K0.5 for
      stimulation of the ATPase depended on the electron-withdrawing characteristics of
      the ring substituents, resulting in a Hammett linear free energy relationship for
      the m- and p-substituted derivatives. The slope of this relationship, with lower
      K0.5 values for electron-withdrawing substituents, suggests that an anionic
      residue in the active site partially discourages binding of this class of
      activators. ortho-Substituted carbonylcyanide phenylhydrazones do not follow this
      relationship, but show lower apparent affinities than expected from their pKa
      values. This finding suggests that steric effects in that region of the binding
      site negatively influence the affinity.

PMID- 9185629
TI  - Assignment of the beta-subunit of wheat eIF2 by protein and DNA sequence analysis
      and immunoanalysis.
AB  - Wheat germ initiation factor 2 (eIF2), like mammalian and yeast eIF2, contains
      three nonidentical subunits. The estimated molecular weights for the wheat
      subunits are 38,000 (p38), 42,000 (p42), and 50,000 (p50). Peptide sequence was
      obtained for the p38 subunit of wheat eIF2 and the resulting amino acid sequence
      suggested that it was actually the equivalent of the mammalian beta-subunit. A
      wheat sprout cDNA expression library was screened with antibody affinity purified
      to the p38 subunit. The DNA sequence of the clones obtained also indicated that
      the p38 subunit was the equivalent to the mammalian beta-subunit. The wheat p38
      subunit was then expressed in Escherichia coli and antibodies raised to the
      purified recombinant protein. Only the p38 subunit of purified wheat germ eIF2
      reacted with the antisera. The p38 subunit of wheat eIF2 is therefore the
      equivalent of mammalian eIF2beta.

PMID- 9185631
TI  - Effect of endoscopic transthoracic sympathicotomy on heart rate variability in
      severe angina pectoris.
AB  - Endoscopic transthoracic sympathicotomy (ETS) is a recently developed technique
      to divide sympathetic nerves. ETS has been shown to improve symptoms and reduce
      ischemia in patients with severe angina pectoris. Low heart rate variability
      (HRV) in patients with ischemic heart disease carries an adverse prognosis. HRV
      reflects autonomic response of the heart and a shift in the sympathovagal balance
      towards parasympathetic dominance could be a marker of improved prognosis. HRV
      might also be used as an indicator of surgical success in sympathetic heart
      denervation. Heart rate was recorded in 57 patients before and after ETS.
      Registration was recorded during controlled respiration in the supine position
      and at tilt test over 10 minutes and spectral analysis was performed. Twenty-four
      hour Holter recordings were analyzed in the time domain. During the controlled
      setting, the high-frequency (HF) component (0.15 to 0.40 Hz) increased
      significantly whereas the low-frequency (LF) component (0.04 to 0.15 Hz) did not
      change significantly. The LF/HF ratio at tilt test was reduced from 1.3 to 0.8 (p
      <0.01). The time-domain analysis showed a significant increase of the mean RR
      interval (923 to 1,006 ms, p <0.001) and indexes reflecting parasympathetic tone
      also increased significantly (the root-mean square of difference measured from
      24.3 to 29.5 ms, p <0.001 and the proportion of adjacent RR intervals >50%
      measured from 5.5% to 8.2%, p <0.01), whereas measurements reflecting global HRV
      did not change. In addition to relief of symptoms and reduced ischemia in severe
      angina pectoris, ETS caused a shift of sympathovagal balance toward
      parasympathetic tone. This might explain the anti-ischemic effect and have
      prognostic implications.

PMID- 9185630
TI  - Management of unstable angina pectoris and non-Q-wave acute myocardial infarction
      in the United States and Canada (the TIMI III Registry).
AB  - Management of Q-wave acute myocardial infarction (AMI) has been shown to differ
      between the United States and Canada, with more catheterization and
      revascularization procedures performed in the United States, but with little or
      no apparent difference in clinical outcomes. No previous studies have evaluated
      management differences for the acute coronary syndromes of unstable angina
      pectoris and non-Q-wave AMI. We therefore compared treatments and outcomes
      between 14 United States and 4 Canadian tertiary care centers participating in an
      observational registry of all consecutive admissions for unstable angina or non-Q
      wave AMI between 1990 and 1993. A random, stratified sample was selected for
      detailed assessment and follow-up. There were 1,733 patients enrolled in United
      States centers and 642 in Canadian ones. In United States centers patients were
      less likely to receive intravenous nitroglycerin, heparin, beta blockers, calcium
      antagonists, or > or = 2 anti-ischemic agents. Coronary arteriography during
      index hospitalization was equally frequent in both countries (63.4% vs 66.9%, p =
      0.781), but at 6 weeks and 1 year coronary arteriography was slightly less
      frequent in the United States patients. Revascularization by coronary angioplasty
      or bypass surgery was equivalent at 6 weeks and 1 year; however, there were
      trends toward less angioplasty and more bypass surgery in the United States than
      in Canada. Patients at United States centers stayed in the hospital fewer days
      than patients at Canadian centers (mean 8.2 vs 12.1 days, p <0.001). Death or AMI
      by 6 weeks was not different (4.8% vs 4.4%, p = 0.633), nor was it different at 1
      year (10.0% vs 10.2%, p = 0.836). The combined outcome of death, AMI, or
      recurrent ischemia was more common in United States than in Canadian patients at
      6 weeks (18.4% vs 13.9%, p = 0.004). Our findings indicate that United States
      physicians and hospitals did not consistently utilize more resources and were not
      more aggressive than their Canadian counterparts when treating acute coronary
      syndromes during this period.

PMID- 9185632
TI  - Angioplasty or surgery for multivessel coronary artery disease: comparison of
      eligible registry and randomized patients in the EAST trial and influence of
      treatment selection on outcomes. Emory Angioplasty versus Surgery Trial
      Investigators.
AB  - The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel
      patients eligible for both percutaneous transluminal coronary angioplasty (PTCA)
      and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding
      survival, myocardial infarction, and major myocardial ischemia. Patients eligible
      for the trial who were not randomized because of physician or patient refusal
      were followed in a registry. This study compares the outcomes of the randomized
      and registry patients. Of the 842 eligible patients, 450 did not enter the trial.
      Their baseline features closely resembled those of the randomized patients and
      follow up was performed using the same methods. In the registry there was a bias
      toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in
      patients with 2-vessel disease (54%). Three-year survival for the registry
      patients was 96.4%, which was better than the randomized patients, 93.4% (p =
      0.044). Angina relief in the registry was equal for CABG and PTCA patients and
      was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p
      = 0.079). Thus, the registry confirms that EAST is representative of all eligible
      patients and does not represent a low-risk subgroup. Since baseline differences
      were small, improved survival in the registry may be due to treatment selection.
      Physician judgment, even in patients judged appropriate for clinical trials,
      remains a potentially important predictor of outcomes.

PMID- 9185633
TI  - Late myocardial ischemic events after saphenous vein graft intervention-
      importance of initially "nonsignificant" vein graft lesions.
AB  - Patients undergoing percutaneous coronary revascularization (PCR) for narrowed
      saphenous vein grafts (SVGs) have a high incidence of subsequent cardiac events,
      but the relative contribution of treated and untreated SVGs, and of native
      coronary narrowings to late events is uncertain. This study evaluated the role of
      progression of SVG disease at untreated sites to cardiac events in these
      patients. All patients with successful PCR of SVG lesions who were enrolled in
      clinical trials with mandated repeat angiography from 1990 to 1994 were studied.
      One hundred three patients (age 63 +/- 8 years, 82% men, ejection fraction 54 +/-
      12%, graft age 8 +/- 4 years), contributing 1,095 analyzable 15- to 25-mm SVG
      segments were followed 29 +/- 13 months (4 patients were lost to follow-up).
      Actuarial event-free (death, myocardial infarction, bypass surgery, or PCR) and
      overall survival at 12 months were 47 +/- 5% and 94 +/- 2%, respectively. Fifty
      six percent of all early (< or = 12 months) events resulted from ischemia from
      recurrence at initially treated SVG sites, 26% at nontreated SVG sites, and 14%
      at nontreated native coronary sites. By 36 months, event-free and overall
      survival were 25 +/- 6% and 86 +/- 4%, respectively. Events occurring > 12 months
      after initial treatment resulted most frequently from ischemia from progression
      of narrowing at untreated SVG sites (46%). Ischemic events from initially
      untreated SVG sites were correlated with initial percent stenosis (initial, 41%
      to 50%; 45% events, 31% to 40%; 18% events, < or = 30%; 2% events, p <0.001) and
      reference SVG diameter (p = 0.003). Recurrent ischemic events from initially
      treated SVG sites were independently correlated with initial percent stenosis
      (initial > 75%; 43% events, 50% to 75%; 27% events, < 50%; 18% events, p = 0.01),
      but not with final percent stenosis. The frequent occurrence of events from
      nontreated 41% to 50% stenoses suggests a need for increased surveillance in
      patients with these lesions. The low incidence of events from initially treated
      lesions < 50% suggests that the hypothesis that "nonsignificant" 41% to 50%
      lesions might best be treated at the time other more severe narrowings are
      treated should be examined.

PMID- 9185634
TI  - Results of directional coronary atherectomy in Northern New England. Northern New
      England Cardiovascular Disease Study Group.
AB  - The role of directional coronary atherectomy (DCA) in interventional cardiology
      remains uncertain. We report the Northern New England regional experience with
      DCA from 1991 to 1994. Data were collected on 11,178 patients having had an
      intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous
      transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of
      interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were
      younger, more often men, had more 1-vessel disease and more coronary artery
      bypass surgery (CABG). DCA was more often used in the left anterior descending
      artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A
      lesions. Angiographic success (96.7%) and clinical success (93%) were good.
      Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial
      infarction 2.8%. After adjusting for case-mix, there was no difference between
      DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence
      interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95%
      CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a
      nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to
      sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to
      5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI
      1.01 to 1.88, p = 0.05). Our results support the relative safety and
      effectiveness of DCA as its use disseminated into the region.

PMID- 9185635
TI  - Use of cilostazol, a novel antiplatelet agent, in a post-Palmaz-Schatz stenting
      regimen.
AB  - We evaluated the therapeutic efficacy of cilostazol, a novel potent inhibitor of
      phosphodiesterase, for the prevention of stent thrombosis following implantation
      of a Palmaz-Schatz stent guided by angiographic visual estimation alone in 71
      patients with 84 lesions. Patients received 81 mg of aspirin 3 times daily and
      100 mg of cilostozol twice daily after angiographic confirmation of optimal
      Palmaz-Schatz stent implantation. Of the 84 vessels stented, 65 (77%) were
      classified as type B2 or C lesions according to the modified American Heart
      Association/American College of Cardiology classification, and 51 (61%) were <3.0
      mm in diameter. Multiple stents were used in 26 patients (31%). The final balloon
      inflation pressure was 18.3 +/- 1.5 atm. The balloon-to-vessel ratio was 1.18 +/-
      0.16. No patient received heparin or warfarin after the procedure. There were no
      deaths, Q-wave myocardial infarctions, in- or out-of-hospital stent thrombosis,
      coronary bypass surgery, or serious side effects such as neutropenia and/or liver
      dysfunction during the 1-month follow-up period. These results indicate that
      cilostazol was a safe and effective antiplatelet agent with minimum side effects
      after Palmaz-Schatz stent implantation.

PMID- 9185636
TI  - Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in
      primary hypercholesterolemia. Atorvastatin Study Group I.
AB  - This double-blind study to evaluate long-term efficacy and safety of atorvastatin
      was performed in 31 community- and university-based research centers in the USA
      to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitor (reductase inhibitor) to an accepted drug of this class in patients
      with moderate hypercholesterolemia. Participants remained on a cholesterol
      lowering diet throughout the study. One thousand forty-nine patients were
      randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo. At 16
      weeks the placebo group was randomized to either atorvastatin or lovastatin
      treatment. At 22 weeks, patients who had not met low-density lipoprotein (LDL)
      cholesterol target levels doubled the dose of reductase inhibitor. Efficacy
      evaluation was mean percent change from baseline in LDL cholesterol,
      triglycerides, total cholesterol, high-density-lipoprotein cholesterol, and
      apolipoprotein B (apoB). Safety profiles as determined by change from baseline in
      laboratory evaluations, ophthalmologic parameters, and reporting of adverse
      events were similar for the 2 reductase inhibitors. After 52 weeks, the
      atorvastatin group maintained a significantly greater reduction in LDL
      cholesterol (-37% vs -29%), triglyceride (-16% vs -8%), total cholesterol (-27%
      vs -21%), and apoB (-30% vs -22%) (p <0.05). More patients receiving atorvastatin
      achieved LDL cholesterol target levels than did lovastatin patients (78% vs 63%,
      respectively), particularly those with coronary heart disease (37% vs 11%,
      respectively). Atorvastatin is highly effective and well tolerated in patients
      with primary hypercholesterolemia with no increased risk of adverse events.

PMID- 9185637
TI  - Relation of ultra-low frequency heart rate variability to the clinical course of
      chronic aortic regurgitation.
AB  - We examined the relation of the standard deviation of the 5-minute mean RR
      intervals over 24 hours (SDANN), a measure of ultra-low frequency heart rate
      variability (HRV) (<0.0033 Hz), and other measures of HRV to clinical outcome
      events in 50 asymptomatic or minimally symptomatic patients with chronic severe
      aortic regurgitation (AR) who underwent ambulatory electrocardiography as part of
      a prospective study of the natural history of regurgitant valvular diseases. At
      entry, all patients were in sinus rhythm and had New York Heart Association
      functional class I or minimal II congestive heart failure, with left ventricular
      (LV) ejection fraction > or = 45% and LV end-diastolic dimension > or = 5.5 cm in
      women and > or = 5.9 cm in men. End points were defined as progression to aortic
      valve replacement (n = 19) or sudden cardiac death (n = 1) during the mean follow
      up period of 8.1 +/- 3.8 years. With the median SDANN of 145 ms as a partition
      value, the average annual risk of end-point events in patients with low SDANN was
      significantly greater than the event rate in patients with high SDANN (11%/year
      vs 2%/year, p <0.0003). In multivariate analysis, reduced SDANN was associated
      with end-point events independent of LV function, LV end-systolic dimension, and
      symptom status (p = 0.001). We conclude that reduced ultra-low frequency HRV
      measured as SDANN is strongly related to progression to valve surgery in
      asymptomatic and minimally symptomatic patients with chronic AR.

PMID- 9185638
TI  - Effects of left ventricular systolic function on left ventricular diastolic
      filling patterns in severe mitral regurgitation.
AB  - Significant mitral regurgitation (MR) may alter the normal pattern of Doppler
      detected left ventricular (LV) filling by causing a prominent early filling (E)
      wave velocity. The manner and extent to which the typical filling pattern of
      uncomplicated MR is affected by concomitant impaired LV systolic function has not
      been characterized. Twenty patients with severe LV systolic dysfunction (2
      dimensional echocardiographic estimation of ejection fraction < or = 30%) and 21
      age- and sex-matched case controls with normal systolic function (ejection
      fraction > or = 55%) were selected. In addition, 20 subjects with normal LV
      systolic function and no MR were analyzed as a reference group. Maximal E-wave
      velocity was increased and highest among MR patients with preserved LV systolic
      function (124 +/- 37 cm/s) than among those with LV systolic dysfunction (101 +/-
      25 cm/s; p <0.05) and normal controls (74 +/- 18 cm/s; p <0.001). Concurrently, A
      wave velocity was lowest in patients with systolic dysfunction and MR (47 +/- 23
      cm/s; p <0.001) than in patients with normal systolic function and MR (79 +/- 33
      cm/s) and normal controls (74 +/- 20 cm/s). Deceleration time of the E wave was
      longest among those with normal systolic function and MR (203 +/- 41 ms) than
      among those with systolic dysfunction and MR (152 +/- 35 ms; p <0.001) and normal
      controls (167 +/- 53 ms; p <0.05). Thus, systolic LV dysfunction in patients with
      severe MR, compared to patients with MR and normal LV systolic function, is
      associated with important changes in diastolic inflow velocities, including
      reduction of the maximal A-wave velocity to a greater extent than the E wave,
      resulting in an increased E/A ratio and shortening of deceleration time of the E
      wave.

PMID- 9185640
TI  - Primary repair of isolated ventricular septal defect in infancy guided by
      echocardiography.
AB  - Between 1989 and 1995, 96 consecutive infants affected by isolated ventricular
      septal defect (VSD) were submitted for primary correction at a median age of 4
      months. Of the 96, 60 (group I) underwent surgery on the base of a 2-dimensional
      Doppler echocardiographic (DD echo) test alone. The preoperative DD echo anatomic
      definition of the type of VSD was confirmed at surgery in all 60 patients without
      false-positive results in terms of additional cardiac anomalies. There were 2
      false-negatives: in 2 patients an associated cardiac anomaly was not detected by
      DD echo and required a second surgical procedure after postoperative cardiac
      catheterization. During the same period 36 infants (group II) underwent surgical
      closure of isolated VSD on the basis of cardiac catheterization and
      angiocardiography in addition to DD echo. The retrospective comparison between
      the 2 groups revealed no significant difference in terms of sensitivity and
      specificity of the diagnostic tools, early and late mortality after surgical
      correction, postoperative hospital stay, and need for late cardiac
      catheterization and surgery. We conclude that after an accurate selection, most
      of the infants with uncomplicated VSD can safely undergo primary repair on the
      basis of DD echo alone.

PMID- 9185639
TI  - Preoperative left ventricular peak systolic pressure/end-systolic volume ratio
      and functional status following valve surgery in patients with mitral
      regurgitation and enlarged end-systolic volumes.
AB  - This study was done to determine if the left ventricular (LV) peak systolic
      pressure/end-systolic volume (PSP/ ESV) ratio predicts symptomatic improvement
      with valve replacement or repair in patients with mitral regurgitation (MR) and
      an enlarged LV ESV. Patients with MR and LV ESV <30 ml/m2 consistently improve
      symptomatically with valve surgery, whereas the response of those with an ESV >30
      ml/m2 is heterogeneous. The LV PSP/ESV ratio, an easily acquired measure of LV
      performance, may discriminate those who improve with valve surgery from those who
      do not. Accordingly, in 40 patients (15 men and 25 women, aged 14 to 74 years)
      with moderate or severe MR, no other cardiovascular abnormalities, and a LV ESV
      >30 ml/m2, we assessed the utility of clinical, hemodynamic, and angiographic
      variables routinely measured preoperatively to predict symptomatic improvement
      with valve replacement or repair. Of the 40 subjects, 3 died during or within 6
      months of surgery. Six months after valve surgery, symptoms had improved in 34
      patients, were unchanged in 1, and had worsened in 2. By univariate analysis,
      only the preoperative pulmonary capillary wedge pressure was predictive of a
      change in functional class (p = 0.05). The PSP/ESV ratio was not predictive of a
      change in functional class after valve surgery. Thus, the PSP/ESV ratio does not
      identify which patients with MR and an enlarged LV ESV will manifest symptomatic
      improvement with valve surgery.

PMID- 9185641
TI  - Shortening of Doppler-derived deceleration time of early diastolic transmitral
      flow in the presence of pulmonary hypertension through ventricular interaction.
AB  - Deceleration time (DT) of the early transmitral flow velocity has recently been
      highlighted as a simple, noninvasive indicator of pulmonary arterial wedge
      pressure. In patients with pulmonary hypertension without left-sided heart
      disease, however, increased right ventricular pressure may result in an abnormal
      ventricular septal motion, which may impact on left ventricular (LV) early
      diastolic filling. We sought to determine if DT may be influenced by the severity
      of pulmonary hypertension in patients without left-sided heart disease. Doppler
      derived transmitral flow and hemodynamic parameters were simultaneously assessed
      in 26 patients with pulmonary hypertension (primary pulmonary hypertension = 11;
      chronic thromboembolism = 15). Transmitral Doppler variables including DT were
      correlated with hemodynamics and LV deformity index measured in early diastole
      with 2-dimensional echocardiography. DT significantly correlated with the total
      pulmonary resistance (r = -0.70, p <0.001). Multivariate analysis revealed that
      DT was independently determined by total pulmonary resistance, but not by
      pulmonary arterial wedge pressure, heart rate, or patient's age in our study
      population. DT showed a correlation with LV deformity index (r = -0.74, p
      <0.001). These results indicate that DT may shorten in association with the
      severity of pulmonary hypertension and that the shortened DT in pulmonary
      hypertension may be attributable to right ventricular pressure overload which
      causes geometric changes.

PMID- 9185642
TI  - Doppler indexes of left ventricular filling after exercise in 50-year-old healthy
      persons.
AB  - Exercise-induced myocardial ischemia has been shown to alter left ventricular
      (LV) diastolic filling. An abnormal response of Doppler indexes of LV filling
      during and after exercise testing has been demonstrated to be a sensitive marker
      of coronary artery disease. A paucity of data is available regarding reference
      values and the physiological variation in LV filling indexes after exercise in
      healthy subjects of similar age. We therefore evaluated 77 healthy subjects (33
      men and 44 women) aged 50 years by Doppler echocardiography at rest and 15 and 60
      minutes after exercise testing. The peak velocity of early diastolic filling (E
      wave), the peak velocity of atrial filling (A-wave), the early to atrial peak
      velocity (E/A) ratio and the deceleration time of early velocity were measured.
      There was a decrease in the E/A ratio 15 minutes after exercise compared with the
      E/A ratio at rest in women (1.13 +/- 0.23 vs 1.23 +/- 0.27; p <0.001) and men
      (1.03 +/- 0.22 vs 1.15 +/- 0.20; p <0.001). The E/A ratio 60 minutes after
      exercise did not differ significantly from rest in women (1.23 +/- 0.27 vs 1.18
      +/- 0.24; p = NS), but men had a lower E/A ratio 60 minutes after than before
      exercise (1.04 +/- 0.23 vs 1.15 +/- 0.20; p <0.001). There was no difference in
      deceleration time of the E-wave before and after exercise. Multivariate analysis
      revealed that the E/A ratio 15 and 60 minutes after exercise was strongly
      independently associated with the E/A ratio at rest (p <0.001) and heart rate 15
      and 60 minutes after exercise (p <0.005) in both women and men. It is concluded
      that there is a physiological decrease in the E/A ratio 15 minutes after exercise
      in healthy subjects, and Doppler LV filling indexes after exercise are strongly
      associated with LV filling indexes at rest and with heart rate.

PMID- 9185643
TI  - Meta-analysis of the morning excess of acute myocardial infarction and sudden
      cardiac death.
AB  - To evaluate the impact of elimination of the morning peak of cardiovascular
      events, we performed a meta-analysis of studies of circadian variation of
      myocardial infarction and sudden cardiac death. The impact would be significant
      because approximately 1 of every 11 acute myocardial infarctions and 1 of every
      15 sudden cardiac deaths are attributable to the morning excess incidence.

PMID- 9185644
TI  - Comparison of the prognostic value of dipyridamole and dobutamine stress
      echocardiography in patients with known or suspected coronary artery disease.
AB  - Direct comparison of the utility of dipyridamole stress echocardiography and
      dobutamine stress echocardiography was performed to identify patients at risk of
      future cardiac events in 134 patients with suspected or known coronary artery
      disease. The predictive values of dobutamine and dipyridamole were remarkably
      similar.

PMID- 9185645
TI  - Comparison of Tc-99m sestamibi perfusion imaging and echocardiography using an
      arbutamine infusion for the detection of coronary artery disease.
AB  - Arbutamine, a synthetic catecholamine, coupled with a closed-loop, computerized
      delivery system was evaluated in conjunction with technetium-99m sestamibi
      scintigraphy and echocardiography for the detection of coronary artery disease.
      Concordance between the imaging methods was 68%, with a similar sensitivity for
      coronary disease using echocardiography (78%) and technetium-99m sestamibi (76%),
      although more arbutamine-induced ischemia was noted with perfusion imaging.

PMID- 9185646
TI  - Does the presence and site of myocardial ischemia on perfusion scintigraphy
      predict the occurrence and site of future myocardial infarction in patients with
      stable coronary artery disease?
AB  - In 47 patients who had undergone myocardial scintigraphy, reversible perfusion
      abnormality was detected in only 28 segments (60%) that were the site of future
      acute myocardial infarction.

PMID- 9185647
TI  - Comparison of six-month results of coronary stenting versus balloon angioplasty
      alone in patients with acute myocardial infarction.
AB  - The purpose of this study was to compare results of delayed elective stent
      implantation on the infarct-related artery with conventional balloon angioplasty
      in 97 patients with acute myocardial infarction at 7 to 10 days after symptom
      onset (stenting in 45 patients, balloon angioplasty in 52 patients). In selected
      patients, intracoronary stent implantation on the infarct-related artery at 7 to
      10 days after symptom onset of acute myocardial infarction is safe, feasible, and
      may reduce the the frequency of late restenosis compared with balloon angioplasty
      (the angiographic restenosis rate: 13% in patients with stents vs 52% in patients
      with balloon angioplasty, p <0.05).

PMID- 9185648
TI  - Are the results of primary percutaneous transluminal coronary angioplasty for
      acute myocardial infarction different during the "off" hours?
AB  - This retrospective study assessed the outcome of primary angioplasty for acute
      myocardial infarction performed during the "off" hours (nights and weekends) or
      during working hours in 288 consecutive patients. The times to admission and
      reperfusion, as well as the in-hospital outcomes, were similar in the 2 groups.

PMID- 9185649
TI  - Transient leftward QRS axis shift during treadmill exercise testing or
      percutaneous transluminal coronary angioplasty is a highly specific marker of
      proximal left anterior descending coronary artery disease.
AB  - The efficacy of transient QRS axis shift to the left as a predictor of proximal
      left anterior descending coronary artery (LAD) disease was assessed. By using
      receiver operating characteristic curve analysis, we indicated that the
      difference in modal QRS axis between before and after exercise was useful in
      detecting proximal LAD disease.

PMID- 9185650
TI  - Effect on survival of previous angina pectoris after acute myocardial infarction.
AB  - Although the present study revealed that previous angina improved in-hospital
      outcome, no further benefit was observed once the patients left the hospital. The
      worse long-term prognosis was associated with multi-vessel coronary disease in
      patients with previous angina.

PMID- 9185651
TI  - Reversible reduction in plasma concentration of nitric oxide induced by cigarette
      smoking in young adults.
AB  - The concentration of nitrate plus nitrite, metabolic end products of nitric
      oxide, in serum prepared from systemic venous blood was significantly (p <0.001)
      decreased in both heavy (14.5 +/- 1.3 micromol/L) and moderate (17.6 +/- 2.3
      micromol/L) smokers relative to that in nonsmokers (22.6 +/- 0.4 micromol/L).

PMID- 9185652
TI  - Clinical significance of an equivocal signal-averaged electrocardiogram.
AB  - Patients with an equivocal signal averaged electrocardiogram (SAECG) had less
      heart disease and better prognosis than patients with overtly abnormal SAECGs. An
      equivocal SAECG should not prompt further invasive diagnostic testing for
      ventricular tachycardia unless other clinical risk factors are present.

PMID- 9185653
TI  - Association of plasma renin activity and echocardiographic left ventricular
      hypertrophy with frequency of new coronary events and new atherothrombotic brain
      infarction in older persons with systemic hypertension.
AB  - In older hypertensive persons, male gender, prior coronary artery disease, prior
      atherothrombotic brain infarction (ABI), and echocardiographic left ventricular
      (LV) hypertrophy are independent risk factors for new coronary events; age, prior
      ABI, and echocardiographic LV hypertrophy are independent risk factors for new
      ABI. The data suggest that high plasma renin activity in hypertensive older
      persons is associated with a high risk of new coronary events and of new ABI
      through its association with echocardiographic LV hypertrophy.

PMID- 9185654
TI  - Effects of dobutamine on aortic valve indexes in asymptomatic patients with
      bileaflet mechanical prostheses in the aortic valve position.
AB  - We investigated the effects of alternating transvalvular flow rate on Doppler
      derived aortic valve resistance and valve area in asymptomatic patients with
      mechanical aortic valve replacement under dobutamine infusion. The Gorlin-derived
      aortic valve area and continuity equation-derived aortic valve area seem to be
      less flow dependent; valve resistance tends to be flow dependent.

PMID- 9185655
TI  - Detection of strands in native aortic valves by transesophageal echocardiography.
AB  - Prevalence and echocardiographic characteristics of strands on the leaflets of
      native aortic valves were examined. According to our data, the strands we found
      in 39% of patients are most likely Lambl's excrescences.

PMID- 9185656
TI  - Digital acoustic analysis of precordial innocent versus ventricular septal defect
      murmurs in children.
AB  - This study examines whether digital acoustic analysis of individual cardiac sound
      components for intensity, timing, and frequency could differentiate between
      innocent and pathologic murmurs. With use of this new technology, sensitive and
      specific criteria can be established for a fast and easy screening procedure to
      help differentiate between innocent and ventricular septal defect murmurs in
      children with suspected heart disease.

PMID- 9185658
TI  - Intake of antioxidants among American cardiologists.
AB  - A survey of 181 cardiologists was conducted to determine their coronary artery
      disease (CAD) risk profile and their intake of antioxidants. The survey reflected
      that the prevalence of CAD risk factors increases with age, as does the
      prophylactic intake of antioxidants (vitamin E was greater than vitamin C, and
      vitamin C was greater than beta carotene).

PMID- 9185657
TI  - Plasma levels of adrenomedullin in primary and secondary pulmonary hypertension
      in patients <20 years of age.
AB  - To elucidate the pathophysiologic significance of adrenomedullin in pulmonary
      hypertension, we measured plasma adrenomedullin-like immunoreactivity (AM-LI)
      concentrations in blood samples obtained from various sites during cardiac
      catheterization by using radioimmunoassay in patients with pulmonary hypertension
      in comparison with patients without pulmonary hypertension. In patients with
      pulmonary hypertension, plasma AM-LI concentrations were significantly elevated
      and there was a significant uptake of AM-LI in pulmonary circulation, indicating
      the involvement of adrenomedullin in the cardiovascular regulation of pulmonary
      circulation in pulmonary hypertension.

PMID- 9185659
TI  - A method providing bidirectional control of coil delivery in occlusions of patent
      ductus arteriosus with shallow ampulla and Pott's shunts.
AB  - A novel method using a snare and bioptome to provide bidirectional control of a
      Gianturco coil for occlusion of a patent ductus arteriosus with a shallow ampulla
      and Pott's shunts is presented. This method greatly reduces the risk of coil
      embolization and optimizes coil position in difficult cases.

PMID- 9185660
TI  - Comparison of intravascular ultrasound measurements at the sites of balloon
      dilatations of femoral arteries with measurements of postmortem gross arterial
      segments at the same sites.
AB  - Intravascular ultrasound measurements of arterial cross-sectional area at the
      site of balloon dilatation are quantitatively accurate and consistent with
      measurements by digital planimetry. Lumen cross-sectional area determinations are
      virtually the same and the minor differences in total arterial cross-sectional
      area are probably related to the dehydration of each specimen, which occurred
      during the interval between studies. Thus, arterial disruption by balloon
      angioplasty does not interfere with the quantitative accuracy of intravascular
      ultrasound measurements.

PMID- 9185661
TI  - Documentation by intravascular ultrasound of thrombus overlying a small
      atheromatous plaque in a coronary artery in unstable angina pectoris and in acute
      myocardial infarction.
AB  - Rupture of atheromatous plaques leading to acute coronary syndromes usually occur
      in lipid-reach and well-developed coronary lesions. We describe 2 unusual
      patients with acute coronary syndromes in whom there was angiographic and
      intravascular ultrasound evidence of an intraluminal thrombus overlying a small,
      nonocclusive plaque in an enlarged coronary artery.

PMID- 9185662
TI  - Use of glucagon for acute intravenous diltiazem toxicity.
AB  - Intravenous diltiazem has become a preferred medication for treating
      supraventricular tachyarrhythmias in hospitalized patients. We present a case of
      inadvertent acute overdosage, its clinical effects, and successful treatment
      using intravenous glucagon.

PMID- 9185663
TI  - Treatment of rat hemiparkinson model with xenogeneic neural transplantation:
      tolerance induction by anti-T-cell antibodies.
AB  - To obtain basic knowledge for the application of xenogeneic neural
      transplantation to patients with Parkinson's disease, the rejection process of
      xenogeneic neural grafts in rats was examined and a therapy to control it was
      developed. Tissues including the ventral mesencephalon were taken from mouse
      embryos and transplanted into the right lateral ventricle of mature male rats.
      Transplanted xenografts were usually rejected by day 15. To prevent the graft
      rejection, host rats were treated with anti-T-cell receptor alphabeta (anti-TCR
      alphabeta) or anti-CD2 monoclonal antibody (mAb) or by a combination of the two.
      Anti-TCR alphabeta (1 mg/kg) and anti-CD2 (7 mg/kg) mAb were administered for 3
      consecutive days (day -2, -1, and 0 of transplantation). Although the
      administration of mAb against either CD2 or TCR alphabeta did not induce
      tolerance, the combination therapy with anti-CD2 and anti-TCR alphabeta mAb
      produced graft survival for more than 100 days. The tolerance induced by this
      combined antibody therapy is antigen specific because rats with long-term
      surviving neural xenograft accepted a second neural graft from the same donor
      strain C3H/He mouse, but not from a third-party strain BALB/c mouse, without
      additional treatment. In addition, T cells isolated from these rats did not
      respond to cultured C3H/He brain cells, but did respond vigorously to BALB/c
      brain cells in mixed lymphocyte reaction. More importantly, the finding that
      xenograft transplantation with the proper treatment reduced the rotation rate of
      6-OHDA-lesioned rats confirmed that surviving grafts functioned properly. The
      results of the present study suggest that xenogeneic neural transplantation in
      combination with T-cell-targeted immunotherapy is an effective approach for
      treatment of Parkinson's disease.

PMID- 9185664
TI  - Overexpression of a neuropeptide nociceptin/orphanin FQ precursor gene,
      N23K/N27K, induces neurite outgrowth in mouse NS20Y cells.
AB  - We recently discovered N23K and its splicing variant N27K as transcripts
      upregulated in mouse NS20Y cells after differentiation induced by dibutylyl
      cyclic AMP (dbcAMP) treatment. N23K and N27K encode precursor proteins for an
      opioid neuropeptide, nociceptin/orphanin FQ, but the transient expression of N23K
      and N27K suggests that it may be involved in neuronal differentiation. In the
      present study, we report that NS20Y cells transfected with N23K and/or N27K but
      not with vector alone formed neurites, with the expressed protein distributed in
      the perinuclear region and distal parts of the neurites. The granular staining of
      the N23K and N27K proteins was also colocalized with secretogranin I, indicating
      incorporation into large dense core vesicles. This cellular targeting of the N23K
      and/or N27K protein is similar to that of dbcAMP-induced processes in
      nontransfected NS20Y cells. In addition, the neurites of transfectants that
      expressed both N23K and N27K were longer than those of the transfectants that
      expressed N23K or N27K alone. Our results demonstrate that N23K and N27K
      participate in the regulation of neurite outgrowth.

PMID- 9185666
TI  - Protein phosphatase inhibitors induce modification of synapse structure and tau
      hyperphosphorylation in cultured rat hippocampal neurons.
AB  - Protein phosphatase inhibitors, okadaic acid and Caliculin A, were used to
      investigate how perturbation of phosphorylation and dephosphorylation processes
      might affect neurite and synapse structure in cultures of fetal rat hippocampal
      neurons. Drug treatments induced neuritic tree modification, with retraction of
      the processes and the appearance of dilatations along the neurites. The
      characteristic dotlike pattern of immunoreactivity of synaptic vesicle proteins
      disappeared. Normal synapses were extremely rare by ultrastructural observation.
      Vesicles of various diameters accumulated in the dilatations, as did organelles
      and amorphous material, suggesting impaired axonal transport.
      Hyperphosphorylation of tau protein was also observed as indicated by the shift
      in the electrophoretic mobility of a 32P-labeled 55-kDa band and by immunoblot
      with epitope-specific tau antibody. Our results show that inhibition of protein
      phosphatases 1 and 2A results in a modification of the neuritic tree structure,
      with loss of neuronal processes, phosphorylation of a tau isoform, and a decrease
      in the number of synapses. These neuronal features are present in Alzheimer's
      disease (AD). Our results suggest that the two events might be related and
      provide a potential link between the biochemical hallmark of AD
      (hyperphosphorylation of tau) and a pathological finding of primary clinical
      relevance (the synaptic loss).

PMID- 9185665
TI  - Molecular cloning of Fyn-associated molecules in the mouse central nervous
      system.
AB  - Fyn tyrosine kinase is expressed extensively in the central nervous system (CNS)
      of mammals, and its genetic disruption in mouse displays several behavioral
      abnormalities with morphological and electrophysiological defects in the brain.
      To understand the signaling pathways in which Fyn is involved in the CNS, we
      screened molecules that directly associate with Fyn in neonatal mouse brain by
      using a two-hybrid yeast system. We isolated five cDNA clones with strong and
      reproducible Fyn-binding activity. Sequence analyses revealed that three of them
      are previously reported molecules, SON, tctex-1, and hnRNP K, and that two clones
      encode novel sequences. The hnRNP K has been shown to associate with Fyn, so our
      yeast system is appropriate to isolate Fyn-binding molecules. Northern
      hybridization analyses indicated that all isolated clones are expressed in the
      mouse brain and that the mRNA levels of the two molecules (tctex-1 and clone 82)
      change during development in the brain. A full-length cDNA of clone 82 was
      obtained and its deduced amino acid sequence was homologous to the RNA-binding
      proteins. Isolation of many Fyn-binding molecules suggest that, in the mouse CNS,
      Fyn mediates multiple signaling pathways by binding to multiple molecules and
      that some of these pathways play critical roles in determining a certain type of
      behavior.

PMID- 9185667
TI  - Ethanol-exposed central neurons fail to migrate and undergo apoptosis.
AB  - Prenatal exposure of human brain to ethanol impairs neuronal migration and
      differentiation and causes mental retardation. The present results indicate that
      the adverse effects of ethanol on brain development may be partly due to the
      ethanol-induced disturbance of neuronal interaction with laminin, a protein
      involved in neuronal migration and axon guidance. This report shows that
      physiological concentrations (IC50 = 28 mM) of ethanol inhibit neurite outgrowth
      and neuronal migration of the rat cerebellar granule neurons on a laminin
      substratum. The ethanol-treated granule neurons undergo apoptosis, degrade their
      laminin substratum, and appear to release and bind increased amounts of the B2
      chain-derived peptides along their surfaces. A protease inhibitor aprotinin, and
      the NMDA receptor channel, and voltage-gated calcium channel antagonist MK801
      partially protect cerebellar granule neurons from ethanol-induced neurotoxicity.
      These results imply that ethanol-treated granule neurons resemble the granule
      neurons of the homozygous weaver mouse cerebellum with respect to their
      apoptosis, laminin expression, and partial rescue by approtinin and MK-801. Thus,
      ethanol may influence neuronal survival and neurite outgrowth via molecular
      pathways similar to those involved in neuronal death in other neurodegenerative
      processes of the central nervous system.

PMID- 9185668
TI  - Effect of a serotonin agonist (sumatriptan) on the peptidergic innervation of the
      rat cerebral dura mater and on the expression of c-fos in the caudal trigeminal
      nucleus in an experimental migraine model.
AB  - The supratentorial cerebral dura of the albino rat is equipped with a rich
      sensory innervation including nociceptive axons and their terminals, which
      display intense calcitonin gene-related peptide (CGRP) immunoreactivity both in
      the connective tissue and around blood vessels. Stereotactic electrical
      stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental
      migraine model, induces marked increase and disintegration of club-like
      perivascular CGRP-immunopositive nerve endings in the dura. Intravenous
      administration of sumatriptan, prior to electrical stimulation, prevents
      disintegration of perivascular terminals and induces accumulation of CGRP in
      terminal and preterminal portions of peripheral sensory axons. Consequently,
      immunopositive terminals and varicosities increase in size; accumulation of
      axoplasmic organelles results in a "hollow" appearance of many varicosities.
      Since sumatriptan exerts its anti-migraine effect by virtue of its agonist action
      on 5-HT1D receptors, we suggest that sumatriptan prevents the release of CGRP
      from dural perivascular terminals by an action at 5-HT1D receptors. In the caudal
      trigeminal nucleus electrical stimulation of the trigeminal ganglion induces, in
      interneurons, increased expression of the oncoprotein c-fos which is not
      prevented by intravenous application of sumatriptan. Disparate findings regarding
      this effect are partly due to the fact that sumatriptan very poorly passes the
      blood-brain barrier and partly to different experimental paradigms used by
      different authors.

PMID- 9185669
TI  - Electron microscopic evidence for microglial phagocytic activity and cholinergic
      cell death after administration of the immunotoxin 192IgG-saporin in rat.
AB  - 192IgG-saporin represents a novel cholinergic immunotoxin which selectively and
      specifically destroys cholinergic cells in rat basal forebrain. Activated
      microglial cells are known to play an important role in phagocytosis in regions
      of neuronal loss. To study the immunotoxin-induced phagocytic events in the basal
      forebrain activated microglial cells were visualized by lectin cytochemistry
      using Griffonia simplicifolia agglutinin and analyzed by electron microscopy.
      Three and 7 days following an intracerebro-ventricular injection of 4 microg
      192IgG-saporin, increased numbers of activated microglial cells were observed at
      both survival times, but the number was strikingly increased at day 7 postlesion.
      Three days after immunotoxin application microglial cells displayed features
      similar to those of resting microglia. Only translucent vacuole-like hollows were
      found intracellularly beneath the plasma membrane of microglial cells and in the
      adjoining extracellular space. Most neurons in the vicinity of microglial cells
      did not show any signs of degeneration. However, 7 days after injection of the
      immunotoxin microglial cells revealed different stages of phagocytosis. The
      majority of microglial cells were localized in perineuronal positions attached by
      processes to large areas of neuronal soma or dendrites, which in general showed
      signs of severe degeneration. The present study provides electron microscopic
      evidence for phagocytic microglial reactions in the rat basal forebrain after
      cholinergic lesion by 192IgG-saporin.

PMID- 9185670
TI  - Transcriptional repression of the growth-associated T alpha1 alpha-tubulin gene
      by target contact.
AB  - In this report, we address the molecular mechanisms that regulate axonal growth
      by focusing on the gene for one of the major axonal cytoskeletal proteins, T
      alpha1 alpha-tubulin. During the developmental growth of sympathetic neurons,
      transcription of a beta-galactosidase transgene driven by the T alpha1 promoter
      (T alpha1:nlacZ) was high until the time of target innervation and neuronal
      maturation, when it decreased significantly. In mature animals, T alpha1:nlacZ
      transcription remained relatively low until target contact was experimentally
      disrupted; when facial motoneurons were axotomized, T alpha1:nlacZ transgene
      expression increased, was maximal for 1-7 days, and, if neurons regenerated and
      reinnervated their target musculature, returned to control levels by 49 days. In
      contrast, if regeneration and reestablishment of target contact were inhibited,
      transgene expression remained elevated. To determine whether this increased
      transcription was due to the loss of target contact or to axonal loss, we
      transected sympathetic neurons that project to the eye either close to or far
      from their cell bodies. In both cases, when target contact was severed, T
      alpha1:nlacZ transcription increased. These experiments indicate that
      transcription of the T alpha1 alpha-tubulin promoter is repressed by target
      contact in both developing and mature neurons. We suggest that this repression is
      due to a target-derived "stop-growth" factor that retrogradely signals to
      regulate transcription of this and other genes that are required for axonal
      growth.

PMID- 9185671
TI  - The pituitary adenylate cyclase-activating polypeptide-induced phosphorylation of
      the transcription factor CREB (cAMP response element binding protein) in the rat
      suprachiasmatic nucleus is inhibited by melatonin.
AB  - The mammalian hypothalamic suprachiasmatic nucleus (SCN) is an endogenous
      pacemaker generating circadian rhythms. SCN activity is synchronized with
      environmental light/dark cycles by photic information primarily transmitted via
      the retinohypothalamic tract (RHT). The SCN controls synthesis and release of
      melatonin, the hormone of the pineal gland. Melatonin itself feeds back to the
      SCN. Using brain slice technique and immunocytochemistry we demonstrate that (1)
      pituitary adenylate cyclase-activating polypeptide (PACAP) induces the
      phosphorylation of the transcription factor cAMP response element binding protein
      (CREB) in the SCN during late subjective day and (2) melatonin inhibits this
      PACAP-induced phosphorylation. Our data suggest that PACAP is a neurotransmitter
      which affects gene expression in the SCN probably via the cAMP signaling pathway
      and that the antagonistic effect of melatonin mirrors a feed-back loop within the
      circadian system.

PMID- 9185673
TI  - Changes in dopamine and acetylcholine release in the rat lateral hypothalamus
      during deprivation-induced drinking.
AB  - Neurochemical changes in the rat lateral hypothalamus during drinking were
      assessed in 20 min sampling intervals, using in vivo brain microdialysis. Water
      deprived animals drank (11 +/- 1 ml) during the hour that water was available.
      Drinking was maximal (7.8 +/- 0.7 ml) during the first 20 min after water
      presentation and minimal during the last 20 min (0.5 +/- 0.4 ml). There was a
      local enhancement in DA turnover evidenced by an increase in the extracellular
      levels of dopamine (DA) (155 +/- 47% during the second sample after water
      presentation as compared to predrinking levels) and dihydroxyphenyl acetic acid
      (DOPAC) (132 +/- 9.7% in the sample that followed water removal). There was also
      an initial increase in the acetylcholine (ACh) release (145.1 +/- 21.7%) during
      the first 20 min after water presentation followed by a reduction (50.12 +/- 18%)
      20 min later. These changes are congruous with previously published results
      suggesting that both neurochemical systems are involved in the regulation of
      water intake. Considering that the exogenous administration of cholinergic drugs
      in this hypothalamic area elicits drinking, the initial increase in ACh release
      could be interpreted as one of the neurochemical events driving this behavior.
      Since the local blockade of D2 receptors has been shown to result in drinking the
      progressive increase in DA turnover detected in this study, as well as the
      concomitant reduction in ACh release, could be involved in drinking attenuation.

PMID- 9185672
TI  - Enhancement of estrogen receptor gene expression in the mediobasal hypothalamus
      during anestrus in the beagle bitch.
AB  - Estrogen receptor mRNA (ER mRNA) levels were measured in the mediobasal
      hypothalamus (MBH) of beagle bitches at different stages of the estrous cycle,
      and compared with levels in ovariectomized (OVX) estrogen-treated bitches. In
      cyclic bitches, the level of hypothalamic ER mRNA increased during the
      progression of anestrus and declined thereafter. Hypothalamic ER mRNA and plasma
      luteinizing hormone (LH) levels during anestrus and proestrus were positively
      correlated (r = 0.94, P < 0.001). In OVX bitches, levels of hypothalamic ER mRNA
      were low, and increased significantly after treatment with a low dose of
      estradiol benzoate. These results suggest that, during the course of anestrus in
      the bitch, hypothalamic ER mRNA expression increases, and may be up-regulated by
      estradiol.

PMID- 9185674
TI  - Neuronal inclusions in the dentate fascia in patients with multiple system
      atrophy.
AB  - Ubiquitin-immunoreactive neuronal inclusions in the granular cells in the dentate
      fascia (UNIDs) of patients with multiple system atrophy (MSA) were examined for
      immunohistochemical and ultrastructural characterization especially in comparison
      with those which were recently reported for amyotrophic lateral sclerosis with
      dementia (ALS-D). Eight of 23 MSA patients had UNIDs which were also identified
      by Gallyas-Braak impregnation but immunonegative for other antibodies including
      against tau, neurofilaments, and alphaB crystallin. Ultrastructurally, loosely
      aggregated fibrils without limiting membrane located around the nucleus, which
      was confirmed by the results of ubiquitin-immunoelectron microscopy. The
      formation of UNIDs in MSA and ALS-D was suggested to be caused by different types
      of degeneration because UNIDs in MSA differ from these in ALS-D in terms of their
      stainability by Gallyas-Braak impregnation and ultrastructurally. In this study
      hippocampal involvement in MSA differing from ALS-D was clarified.

PMID- 9185675
TI  - Sequential activation of supplementary motor area and primary motor cortex during
      self-paced finger movement in human evaluated by functional MRI.
AB  - The 'Bereitschaftspotential' attributed to activation of the supplementary motor
      area (SMA) precedes the 'motor potential' of the primary motor cortex (Ml) about
      500-1000 ms during self-initiated movements. A measurement procedure is reported
      to evaluate the sequence of hemodynamic activation within both motor areas by
      functional magnetic resonance imaging (fMRI). The fMRI-data were averaged across
      multiple trials of single voluntary finger movements and analyzed with respect to
      the onset-time of signal increase. All participants showed a sequential
      hemodynamic response with SMA preceding M1 activation. The mean latency between
      hemodynamic activation of SMA and M1 amounted to 0.8 s. These findings suggest
      that the vascular response parallels the electrical events and that a sufficient
      temporal resolution can be achieved by fMRI to detect sequential hemodynamic
      activation of functionally connected cortical areas.

PMID- 9185676
TI  - Decreased heart rate by acupuncture stimulation in humans via facilitation of
      cardiac vagal activity and suppression of cardiac sympathetic nerve.
AB  - The effect of acupuncture stimulation applied to a Ximen point (P4) of a forearm
      on heart rate was studied in healthy volunteer human subjects. Acupuncture
      stimulation decreased heart rate, or gave no significant response. The decreased
      response of heart rate following acupuncture was attenuated by administration of
      atropine and propranolol. Therefore, the acupuncture-induced response of decrease
      in heart rate was concluded to be a result of a reciprocal coordination of an
      increase in cardiac vagal activity and a decrease in cardiac sympathetic
      activity.

PMID- 9185677
TI  - Chloroquine administration in mice increases beta-amyloid immunoreactivity and
      attenuates kainate-induced blood-brain barrier dysfunction.
AB  - The anti-malarial drug chloroquine (CHL) has been reported to cause the
      accumulation of beta-amyloid peptide containing fragments (fA beta) of the
      amyloid precursor protein within lysosomes in vitro. However, the significance of
      this finding with regards to the development of Alzheimer's disease (AD)
      pathology in vivo is not known. Hence, we investigated the effects of chronic CHL
      administration in the mouse. Systemically administered CHL caused an astrocytic
      response and an increase in intracellular A beta immunoreactivity throughout the
      brain, but no plaque-like pathology. Pharmacological challenge with the
      excitotoxin kainic acid (KA) revealed a mild proconvulsant effect of CHL
      pretreatment (P < 0.06). Interestingly, CHL protected the blood-brain barrier
      from characteristic KA-induced dysfunction. Given the hypothesized involvement of
      both excitotoxic processes and the vascular system in AD, the observed
      interactions may assist in elucidating the pathogenesis of AD.

PMID- 9185678
TI  - Induction of macrophage inflammatory protein MIP-1alpha mRNA on glial cells after
      focal cerebral ischemia in the rat.
AB  - The distribution and cell source of macrophage inflammatory protein-1alpha (MIP
      1alpha) mRNA induced by transient and permanent middle cerebral artery occlusion
      (MCAO) were investigated by a double in situ hybridization technique. The
      distribution and time course of the induction of MIP-1alpha mRNA were similar in
      the two MCAO models. MIP-1alpha mRNA was not detected in the sham-operated rat
      brain. MIP-1alpha mRNA was induced by MCAO with the peak of expression at 4-6 h
      after the onset of occlusion, and the signals of MIP-1alpha mRNA were observed in
      the ischemic core region at an earlier time point, and thereafter intensely in
      the penumbra of the ischemic area. The signals of MIP-1alpha mRNA were evident on
      Mac-1alpha mRNA-positive cells, but not on glial fibrillary acidic protein (GFAP)
      mRNA-positive cells, indicating that MIP-1alpha mRNA was induced in
      microglia/macrophages of the rat brain after focal cerebral ischemia.

PMID- 9185679
TI  - Brain derived neurotrophic factor induces a rapid upregulation of synaptophysin
      and tau proteins via the neurotrophin receptor TrkB in rat cerebellar granule
      cells.
AB  - We have examined the effects of neurotrophins brain derived neurotrophic factor
      (BDNF) and nerve growth factor (NGF) on the expression of the maturation-specific
      proteins synaptophysin and tau, and the growth-associated protein (GAP)-43 in
      cerebellar granule cells. We find that BDNF but not NGF rapidly (within 2 h)
      upregulates levels of synaptophysin, tau and c-Fos correlating with expression of
      the neurotrophin receptor TrkB. The rapid increase in synaptophysin is not
      preceded by c-Fos elevation suggesting a post-transcriptional mechanism may be
      involved. In contrast, no upregulation of GAP-43 levels are seen within this time
      period. Phorbol ester mimics the effects of BDNF, indicating that protein kinase
      C (PKC) is either a component of, or feeds into the signalling mechanism. We
      conclude that BDNF, characterized to be survival promoting early in
      differentiation of cerebellar granule cells, enhances maturation at a later
      stage.

PMID- 9185680
TI  - Frequency-dependent expression of diaphorase staining and nNOS-immunoreactivity
      in rat dorsal horn neurones following C-fibre stimulation.
AB  - Recent evidence demonstrated that lesion-induced central nervous system changes
      are at least partly mediated by the action of the gaseous transmitter nitric
      oxide (NO). We investigated the hypothesis that the frequency of peripheral C
      fibre stimulation determines the number of neurones in the dorsal horn that can
      be visualised immunohistochemically with antibodies to NO synthase (NOS) or using
      the NADPH-dependent diaphorase (NDP) reaction. C-fibre stimulation of the sciatic
      nerve at a frequency of 0.01 Hz was followed by a significant increase in NDP
      cell number in the spinal segment L3, whereas 0.1 and 1 Hz stimulation resulted
      in a significant decrease. Neuronal NOS (nNOS)-immunoreactivity was significantly
      influenced only by 1 Hz stimulation and only on the ipsilateral side in L3. Here,
      the number of nNOS-immunoreactive (ir) neurones decreased significantly in the
      superficial dorsal horn. The results show that the system of NDP-neurones is
      capable of displaying a bidirectional response depending on the frequency of C
      fibre input.

PMID- 9185681
TI  - Differential outcomes from magneto- and electroencephalography for the analysis
      of human cognition.
AB  - Theoretical considerations show that magnetoencephalography (MEG) and
      electroencephalography (EEG) provide different information about ongoing human
      brain activity. The paper presents simultaneously measured MEG and EEG data
      showing that these measures may lead to different conclusions about cognitive
      models under investigation. This was demonstrated for amplitude results of the
      P300/N400 complex in a study of the secondary processing of lexical and non
      verbal information in visual stimuli. As both methods provide different
      information about ongoing brain activity, their combined analysis is valuable.
      This seems particularly true for studies of higher order cognitive processing.

PMID- 9185682
TI  - The effect of topical turpentine on the functional properties of cutaneous
      afferents in the anaesthetized rat.
AB  - Turpentine was applied to the rat dorsal hindpaw over 1.5-3.5 h and afferent
      activity was recorded for 1.5-7 h after its removal. Increased spontaneous
      activity from both A- and C-fibres was observed. There was an increase in units
      with no response to natural stimuli and a reduction in the numbers of all types
      of afferent unit, with some recovery of the C- and A delta-classes during the
      recording period. Surviving C-polymodal nociceptor units had normal sensitivity
      to noxious heat, but higher mechanical thresholds. Thus turpentine application
      caused no nociceptor sensitization. Instead, the many insensitive units plus the
      generalized spontaneous firing may be signs of non-specific axonal damage. A
      general division of irritant chemicals into those that are predominately
      damaging, like turpentine, and those that generate specific nociceptor firing or
      sensitization, is proposed.

PMID- 9185683
TI  - beta-Amyloid (A beta) deposition in the medial temporal lobe of patients with
      dementia with Lewy bodies.
AB  - The distribution and density of diffuse, primitive and classic beta-amyloid (A
      beta) deposits in the medial temporal lobe (MTL) was studied in cases of dementia
      with Lewy bodies (DLB) with and without associated Alzheimer's disease (AD) and
      15 cases of sporadic AD. In the 'pure' DLB cases, virtually no A beta deposits
      were observed in the CA regions of the hippocampus or dentate gyrus whereas
      deposits were distributed throughout the MTL in DLB/AD and AD cases. Densities of
      diffuse and primitive A beta deposits were similar in AD and DLB/AD cases but
      density was significantly reduced in the 'pure' DLB cases. The density of the
      classic deposits was significantly reduced in DLB cases with or without
      associated AD compared with AD cases. These results suggest that A beta
      deposition in the MTL in 'pure' DLB cases is similar to that of elderly non
      demented patients while, with the exception of the classic deposits, A beta
      deposition in DLB/AD cases is similar to that in cases of AD alone.

PMID- 9185684
TI  - Pre-attentive processing of spectrally complex sounds with asynchronous onsets:
      an event-related potential study with human subjects.
AB  - Neuronal mechanisms involved in the processing of complex sounds with
      asynchronous onsets were studied in reading subjects. The sound onset asynchrony
      (SOA) between the leading partial and the remaining complex tone was varied
      between 0 and 360 ms. Infrequently occurring deviant sounds (in which one out of
      10 harmonics was different in pitch relative to the frequently occurring standard
      sound) elicited the mismatch negativity (MMN), a change-specific cortical event
      related potential (ERP) component. This indicates that the pitch of standard
      stimuli had been pre-attentively coded by sensory-memory traces. Moreover, when
      the complex-tone onset fell within temporal integration window initiated by the
      leading-partial onset, the deviants elicited the N2b component. This indexes that
      involuntary attention switch towards the sound change occurred. In summary, the
      present results support the existence of pre-perceptual integration mechanism of
      100-200 ms duration and emphasize its importance in switching attention towards
      the stimulus change.

PMID- 9185685
TI  - The genotype 2/2 of the presenilin-1 polymorphism is decreased in Spanish early
      onset Alzheimer's disease.
AB  - We have found a significantly lower frequency of the presenilin-1 (PS-1) intronic
      polymorphism 2/2 genotype in early-onset Alzheimer's disease (AD) patients
      without APOE epsilon4 alleles (2/2 = 0.054; P = 0.009) as compared to age matched
      non-epsilon4 controls (2/2 = 0.227). Moreover the average age of onset in AD
      patients with the PS-1 2/2 genotype is older than that in AD patients with a 1/2
      genotype or with a 1/1 genotype. This data suggest a protective effect of the 2/2
      genotype which would delay the age of onset in AD. Our results do not support an
      association between the 1/1 genotype and AD. However, a non-significant increase
      of the 1/1 genotype is found in non-epsilon4 AD patients (P = 0.20).

PMID- 9185686
TI  - Long-term potentiation in perforant path/granule cell synapses is associated with
      a post-synaptic induction of proenkephalin gene expression.
AB  - Enkephalin peptides released from hippocampal mossy fibres lower the threshold
      for the generation of long-term potentiation (LTP) at the mossy fibre synapses.
      High frequency stimulation of the hippocampal dentate gyrus, sufficient to induce
      mossy fibre LTP, is associated with increased expression of the proenkephalin
      gene in the granule cells. We show here that a similar elevation in proenkephalin
      mRNA levels is observed, in anaesthetised rats, following stimulation of the
      perforant path sufficient to induce LTP in the perforant path/granule cell
      synapses. This strengthens the evidence implicating granule cell enkephalins as
      mediators of functional plasticity in the hippocampus. Furthermore. the results
      hint at a form of 'domino plasticity', where potentiation of transmission at the
      perforant path/granule cell synapses is subsequently followed by an enkephalin
      mediated potentiation of transmission at the mossy fibre synapses.

PMID- 9185687
TI  - Conversion of biocytin labelled cells and structures for the confocal laser
      scanning method.
AB  - The method for converting biocytin preparations of brain sections fills a gap in
      the application of confocal laser-scanning microscopy. Both neuronal and non
      neuronal structures are converted. The background remains free of staining. The
      protocol can be applied to old and already existing biocytin-(diaminobenzidine)
      nickel preparations which are then made accessible to evaluation with the laser
      scanning microscope by the substitution of nickel with silver-gold. Sodium
      thiosulphate is used to remove the unbound silver. The reflection image of the
      laser-scanning microscopy provides more information than the transmission image.

PMID- 9185688
TI  - Neuropeptide Y hyperpolarizes submucosal neurons of the guinea-pig descending
      colon.
AB  - Effects of neuropeptide Y (NPY) on submucosal neurons of the guinea-pig
      descending colon were investigated electrophysiologically by means of
      intracellular electrophysiological recordings. NPY (100 nM) induced a marked and
      prolonged hyperpolarization, accompanied by a decrease in input resistance in
      most (90%) neurons. This NPY-induced hyperpolarization was diminished and
      augmented by membrane hyperpolarization and depolarization, respectively. The NPY
      hyperpolarization was not affected by exposure to either calcium-free solutions
      or the alpha2-adrenoceptor antagonist, idazoxan (1 microM). When more than one
      peptide was applied to a neuron, NPY, PYY and Pro34-NPY were equipotent, whilst
      NPY13-36 was less potent. It was concluded that NPY hyperpolarized submucosal
      neurons of the guinea-pig descending colon, possibly via a direct action on
      postsynaptic Y1-receptor and increasing potassium conductance.

PMID- 9185689
TI  - Oesophageal cancer in France: potential importance of hot alcoholic drinks.
AB  - In France, major geographic variation exists in the incidence of oesophageal
      cancer, the highest incidence being reported in Normandy and Brittany. The role
      of alcohol in the risk of oesophageal cancer is well established in Western
      countries. One possible explanation for geographical variation of incidence is
      that higher incidence of oesophageal cancer is due to specific local alcoholic
      beverages. The aim of this study was to determine whether different types of
      alcoholic beverages exert different effects on the risk of oesophageal cancer,
      and whether the variation of incidence in France is due to variation in local
      drinking behaviour. We conducted a multicentre case-control study in 3 regions of
      France (Normandy, Burgundy and Midi-Pyrenees), among which there is a 5-fold
      variation in incidence. We selected 208 cases and 399 controls, all males. During
      the interview, the subject's entire alcohol history was reconstituted, noting
      each type of alcoholic beverage consumed throughout life. The link between the
      risk of oesophageal cancer and alcohol varies greatly according to the type of
      alcoholic beverage, with aniseed aperitifs, hot spirits (especially hot Calvados)
      and beer carrying the highest risk. Consumption of hot Calvados appeared to
      explain about 2/3 of the inter-regional and urban/rural differences in incidence,
      whereas total alcohol intake explained less than 1/5. Even after adjustment for
      all other alcoholic beverages, consumption of hot calvados explained almost half
      of the peak in incidence of oesophageal cancer in the Northwest of France, as
      well as half of the urban/rural differences in incidence.

PMID- 9185690
TI  - A case-control study of diet and lung cancer in northeast China.
AB  - A case-control study involving interviews with 227 lung-cancer cases and 227
      matched hospital controls was conducted in Heilongjiang Province in northeast
      China to examine the influence of dietary factors on the risk of developing lung
      cancer. Lung-cancer cases were all incident cases judged to be suitable
      candidates for tumor removal by surgery. Controls were selected among
      hospitalized patients with non-neoplastic and non-lung disease. The overall male
      lung-cancer risks associated with cigarette smoking were similar to those
      reported in other Chinese studies but quite low compared to risks in Western
      countries. However, the subjects in this study were relatively young (average age
      53.2), had started to smoke on average at a relatively old age (21.3 years), and
      only smoked an average of 18.7 cigarettes per day. Lung-cancer risk was not
      strongly associated with any of the nutrients examined, when all cases were
      compared to all controls. However, the data were suggestive of differences in the
      relationship of diet to risk among smokers and non-smokers. Cautious
      interpretation is required because of the wide confidence intervals due to
      limited sample size. Among the smokers, only higher beta-carotene was associated
      with estimates suggesting a lowered risk. Among non-smokers, the evidence
      suggested that increased vegetable consumption might reduce risk, consumption of
      any fruit might reduce risk but beta-carotene was unrelated to risk. The
      differences observed in the relationship of diet to lung-cancer risk between
      Chinese smokers and non-smokers warrant further study.

PMID- 9185691
TI  - Analysis of the T cell response to tumor and viral peptide antigens by an
      IFNgamma-ELISPOT assay.
AB  - We have established a sensitive ELISPOT assay measuring interferon gamma (IFN
      gamma) release on a single-cell basis to detect influenza peptide-specific CD8+ T
      cells in uncultured peripheral blood mononuclear cells (PBMC). Using this method,
      we studied the T cell response to HLA-A1 and HLA-A2.1 binding peptide epitopes
      derived from the MAGE-1 and MAGE-3 proteins, from the melanoma-associated
      antigens tyrosinase, Melan-A/MART-1 and gp100, and from influenza proteins in
      stage IV melanoma patients and healthy controls. In 18 of 24 HLA-A2-positive
      donors (75%), but only in 9 of 25 HLA-A2-positive melanoma patients (36%) T cells
      reactive with the influenza matrix peptide were demonstrated (p = 0.007). T cells
      responding to one or several of the melanoma-associated peptides were detected in
      5 of 25 HLA-A2-positive patients with metastatic melanoma. Four of these 5
      patients had been treated with interleukin-2- and IFN alpha-containing therapy.
      Two of the 24 healthy donors had T cells reactive with the MART-1 27-35 peptide.
      No reactivity with the HLA-A1-binding peptides from MAGE-1 or MAGE-3 was detected
      in any of the HLA-A1-positive healthy controls or melanoma patients. These
      results show that the IFN gamma-ELISPOT assay is suitable to determine
      quantitatively T cells reactive with melanoma-associated and influenza peptide
      epitopes in uncultured PBMC. The failure to detect T cells responding to
      influenza in many melanoma patients with progressive disease may indicate an
      impairment of their T cell function.

PMID- 9185692
TI  - Photodynamic therapy: an effective, but non-selective treatment for superficial
      cancers of the oral cavity.
AB  - It has often been claimed that photodynamic therapy (PDT) produces selective
      destruction of small cancers without affecting the adjacent normal tissue. The
      objective of our work was to treat small cancers of the oral cavity with PDT and
      subsequently excise the treated areas for histological studies of tumour and
      adjacent normal tissue exposed to the same light dose. Eleven patients with
      histologically proven T1NO oral squamous-cell carcinomas were treated with PDT,
      using Photofrin as a sensitiser. The tumours plus a surrounding cuff of normal
      tissue were exposed to 50 J/cm2 non-thermal laser light at 630 nm delivered by
      surface illumination and the treated areas subsequently excised. Histological
      staining and image analysis were used to determine the nature and extent of
      injury. No macroscopic distinction was evident between tumour and normal tissue
      exposed to light. Histologically, replacement of superficial epithelium, tumour
      and connective tissue with a fibrinous necrotic slough was seen. There was also
      loss of endothelium from small vessels, with haemorrhage and thrombosis.
      Preservation of subepithelial collagen and elastin was demonstrated with EVG
      staining. No evidence of selective tumour necrosis was found. Although depth of
      injury was variable, full thickness mucosal necrosis occurred in all cases.

PMID- 9185693
TI  - Integrated Epstein-Barr virus (EBV) and chromosomal abnormality in chronic active
      EBV infection.
AB  - In order to examine the role of Epstein-Barr virus (EBV) in the pathogenesis of
      chronic active EBV infection (CAEBV), we investigated whether or not EBV
      integration into the human genome is associated with any chromosonal abnormality.
      We therefore analyzed 4 cases of CAEBV: 2 cases showed a normal karyotype, while
      one had an oligo-clonal 6th chromosomal abnormality and the fourth had a clonal
      6th deletion (q15q23). In addition, the case with an oligo-clonal abnormality
      also had oligo-clonal EBV terminal repeat (TR) bands, while the case with a
      clonal abnormality showed a clonal TR band. In contrast, the 2 cases with a
      normal karyotype showed no clonal band. Two-color fluorescence in situ
      hybridization (FISH) was used to detect the integrated EBV and the 6th
      chromosomal site. The presence of integrated EBV into the 6th chromosome was not
      frequent in the 2 cases with a normal karyotype, but it was statistically
      frequent in the case with an oligo-clonal 6th abnormality. In the case with a
      clonal 6th deletion, integration in the 6th chromosome was also slightly higher
      than that in the other chromosomes. In CAEBV, integrated EBV might thus be
      associated both with chromosomal abnormality and with pathogenesis.

PMID- 9185694
TI  - Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of
      Women's Health Study Group.
AB  - We have examined the effect of tubal sterilisation and hysterectomy on risk of
      ovarian cancer in a large case-control study in eastern Australia involving 824
      women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and
      1993, and 855 controls randomly selected from the electoral roll. Relative risks
      for ovarian cancer were estimated using multiple categorical regression to adjust
      for age, parity, oral contraceptive use and other risk factors. Tubal
      sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR
      0.61, 95% CI 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% CI
      0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective
      of sterilisation technique, and estimates were similar among various types of
      epithelial ovarian cancer. The greatest reduction (74%) was observed among women
      with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or
      contraceptive foams were not related to ovarian cancer, while use of talc in the
      perineal region slightly but significantly increased risk among women with patent
      fallopian tubes. Reportedly heavy or painful menses, perhaps associated with
      retrograde flow, were associated with ovarian cancer, and reduction in risk of
      disease after hysterectomy was greatest among women who had heavy periods. Our
      findings support the theory that contaminants from the vagina, such as talc, and
      from the uterus, such as endometrium, gain access to the peritoneal cavity
      through patent fallopian tubes and may enhance the malignant transformation of
      ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of
      ovarian cancer by preventing the access of such agents.

PMID- 9185695
TI  - Mutations of p53 tumor-suppressor gene in angiosarcoma.
AB  - Transgenic mice deficient for the p53 gene were reported to frequently develop
      angiosarcoma (AS), suggesting that alterations in the gene are associated with
      tumorigenesis of AS. However, little is known about genetic changes, including
      p53 gene alterations, in human AS because of its rarity. We analyzed p53
      mutations on paraffin-embedded specimens from 33 patients with AS by polymerase
      chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by
      direct sequencing. Age of patients ranged from 18 to 91 (median 70) years, with a
      male to female ratio of 1.5:1. Sites of tumor were the head in 13 patients, the
      trunk in 4, the extremities in 4, the heart in 4, bones in 2 and others in 6. PCR
      SSCP revealed aberrant mobility shifts of bands in 17 cases: 11 in exon 5, 5 in
      exon 7 and 4 in exon 8. Direct sequencing on these 17 cases revealed a total of
      20 mutations. The frequency of p53 mutations was different by site of tumors: 7
      of 13 in head, all 4 in extremities, 2 of 4 in heart and none of 4 in trunk. Our
      findings suggest that occurrence of p53 mutation is a major pathway for
      development of human AS.

PMID- 9185696
TI  - Breast implants and cancer risk in Denmark.
AB  - Although millions of women worldwide have received breast implants for cosmetic
      or medical reasons, possible late effects (in particular cancer) have not been
      well studied. To provide quantitative information on cancer occurrence among
      women undergoing breast implant surgery, 1,135 women treated for cosmetic reasons
      in Denmark were evaluated. Patients were identified using the nationwide Hospital
      Discharge Registry with linkage to the nationwide Danish Cancer Registry to
      determine subsequent cancer incidence. The average age of the women at implant
      surgery was 31 years, and the average follow-up was 8.4 years, up to a maximum of
      17 years. Overall, 27 cancers developed after implant surgery compared with 24.7
      expected based on incidence rates from the general population (standardized
      incidence ratio [SIR] = 1.1; 95% CI: 0.7-1.6). Eight breast cancers were observed
      vs. 7.8 expected (SIR = 1.0; 95% CI: 0.4-2.0). No evidence was found to link
      breast implants with increased cancer risk in the decade after surgery. While the
      results are encouraging, longer follow-up into later life will be necessary to
      assess fully any possible adverse effects.

PMID- 9185697
TI  - The Bax alpha:Bcl-2 ratio modulates the response to dexamethasone in leukaemic
      cells and is highly variable in childhood acute leukaemia.
AB  - Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of
      stimuli, whereas a predominance of Bax alpha to Bcl-2 accelerates apoptosis upon
      apoptotic stimuli. We sought to study the relevance of these apoptotic regulating
      gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines
      (HL60, DoHH2, CEM C7, L1210 and S49), the Bax alpha-to-Bcl-2 ratio as assessed by
      Western-blot analysis correlated with sensitivity to dexamethasone treatment. In
      addition, in HAbax alpha-transfected CEM C7 clones, a similar correlation was
      found for dexamethasone and thapsigargin sensitivity. In bone-marrow aspirates
      from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n
      = 48; AML, n = 8), the Bcl-2 and Bax alpha levels were highly variable, but well
      within the range found in the Bax alpha transfectants and in the established cell
      lines. Bcl-2 levels were lower in T- than in B-lineage ALL, which could be
      ascribed to simultaneous inverse relation between Bcl-2 and WBC. By contrast, Bax
      alpha:Bcl-2 was independent of any presenting feature and was largely dependent
      on Bax alpha levels. Results suggest that Bax alpha:Bcl-2, rather than Bcl-2
      alone is important for the survival of drug-induced apoptosis in leukemic cell
      lines and ALL.

PMID- 9185698
TI  - Pro-protein convertase gene expression in human breast cancer.
AB  - As a first step towards elucidating the role that pro-protein convertases play in
      the growth regulation of breast cancer, we studied the gene expression of 6 known
      human convertase members (PC1/PC3, PC2, furin/PACE, PACE4, PC5/PC6 and PC7/LPC)
      in human breast cancer tumors and cell lines. PC1, furin, PACE4 and PC7 mRNAs
      were detected by reverse transcriptase-polymerase chain reaction (RT-PCR)
      amplification in all 7 human breast cancer cell lines and 30 breast tumor tissues
      tested. PC5 expression was detected in 2/30 tumor tissues. PC2 mRNA, however, was
      not detected. In situ hybridization localized furin mRNA to the tumor cells;
      adjacent fibrous stroma and blood vessel elements were negative for furin gene
      expression. Thirty breast tumors with varying quantities of estrogen and
      progesterone receptors were assayed for furin, PACE4 and PC1 mRNAs by
      quantitative RT-PCR, and 22 tumors were assayed for PC7 mRNA. An apparent
      association was observed only between PACE4 and estrogen receptors. No
      statistically significant correlation was found between the levels of steroid
      receptors and the expression of human furin, PCI and PC7 genes. Convertase mRNA
      levels appeared similar in both the estrogen-responsive and -unresponsive breast
      cancer cell lines. Also, proprotein convertase mRNAs were not detected in 9
      histologically normal human breast tissues. These results suggest that elevated
      expression of some members of the pro-protein convertase gene family is a
      characteristic of human breast cancer, an event which may be important for human
      breast tumorigenesis.

PMID- 9185699
TI  - T-cell receptor CDR3 size distribution analysis to evaluate specific T-cell
      response to cancer vaccines.
AB  - To evaluate immunization procedures in cancer patients, it is important to define
      which biological parameters reflecting a specific immune response to the vaccine
      should be followed. One of these may be the recruitment or expansion of clonally
      amplified T-cell subpopulations previously primed by tumor-specific antigen that
      could be detected in tiny samples by CDR3 length analysis of T-cell receptor
      Vbeta transcripts. To evaluate this procedure, we studied one patient with
      metastatic colorectal adenocarcinoma who had received 4 intradermal injections of
      irradiated autologous tumor cells plus IL-2 on days 1, 8, 15 and 36. Skin tests
      for delayed type hypersensitivity (DTH) reaction to irradiated autologous tumor
      cells were performed on days 1 and 43. Although no change was observed in day 43
      PBMCs, some recurrent transcripts were detected with similar CDR3 size patterns
      in both vaccine and DTH sites. Fine analysis of these Vbeta-Cbeta PCR products
      with Jbeta primers confirmed that transcripts with similar length were recruited
      in both vaccine and DTH sites. Induction of an inflammatory response in both DTH
      and vaccine sites may therefore be associated with the recruitment of few T-cell
      clonotypes. In addition, a Vbeta15-Jbeta2.5 transcript similar to those detected
      in vaccine and DTH sites was also identified in enzymatically dissociated tumor
      cells and in a tumor fragment. Sequencing confirmed that an identical junctional
      sequence was shared by Vbeta15-Jbeta2.5 transcripts from both DTH and tumor
      samples. Our results indicate that a T-cell clone similar to the one amplified in
      the tumor was recruited at the vaccine and DTH reaction sites. We therefore
      suggest that such an approach would be useful in assessing specific expansion of
      T-cell clones induced by cancer vaccines.

PMID- 9185700
TI  - Differences in the recognition of tumor-specific CD8+ T cells derived from solid
      tumor, metastatic lymph nodes and ascites in patients with gastric cancer.
AB  - We established gastric cancer-specific CD8+ T-cell (T(CD8+)) lines derived from
      different lymphocyte sources in the same patients by repeated stimulation with
      mitomycin-C-treated autologous tumor cells with low-dose interleukin-2, and we
      compared recognition patterns among the T(CD8+) derived from solid tumor, lymph
      node metastasis and ascites in the same patient (n = 3) to determine their
      similarities and differences for therapeutic purposes. We confirmed that gastric
      cancer-specific T(CD8+) lines can be isolated, in a MHC class I-restricted
      manner, from solid tumors, metastatic lymph nodes and malignant ascites. T(CD8+)
      lines derived from tumor-infiltrating lymphocytes (TIL) in solid tumor recognized
      autologous tumor cells derived from solid tumor, but not autologous tumor cells
      derived from ascites or metastatic lymph node, while T(CD8+) lines derived from
      tumor-associated lymphocytes (TAL) in malignant ascites recognized autologous
      tumor cells derived from ascites, but not tumor cells from solid tumor or
      metastatic lymph node. Furthermore, T(CD8+) lines derived from regional lymph
      node lymphocytes (RLNL) recognized autologous tumor cells derived from metastatic
      lymph nodes, but not tumor cells derived from ascites. No significant differences
      were seen in MHC class I expression among the tumors derived from solid tumor,
      lymph node metastasis or ascites in the same patient. This suggests that there
      are differences of recognition patterns among the TILs, TALs and RLNLs in the
      same patient and that it is important to consider the source of lymphocytes,
      e.g., a combination of TILs, TALs and RLNLs, for adoptive immunotherapy in
      gastric cancer patients.

PMID- 9185701
TI  - Baldness and other correlates of sex hormones in relation to testicular cancer.
AB  - There is evidence that sex hormones and intrauterine factors are involved in the
      etiology of testicular cancer. We evaluated the importance of perinatal and adult
      life correlates of sex hormones as risk factors for testicular cancer in a case
      control study of 97 incident, histologically confirmed cases, residents of the
      Greater Athens area and environs, who were diagnosed in the 3 specialized cancer
      hospitals and the major General Hospital in Athens during the 2 year period 1993
      94. Cases were age-matched to 2 healthy controls from the same study base. Both
      cases and controls as well as their mothers were interviewed by the same
      investigator and the data were analyzed through conditional logistic regression.
      The odds ratio for testicular cancer was elevated among persons born after a
      pregnancy characterized by severe nausea. Among the adult life factors, higher
      body mass was associated with reduced risk, as was evidence of baldness. To the
      extent that nausea during pregnancy reflects higher levels of pregnancy estrogens
      on the one hand, and baldness is linked to androgens on the other, our data
      suggest that estrogens in the intrauterine life and androgens at later stages may
      have sequential opposing effects for the development of testicular cancer.

PMID- 9185702
TI  - Influence of spatial configuration on the expression of carcinoembryonic antigen
      and mucin antigens in human bladder cancer.
AB  - CEA and cellular mucin antigens have been recognized as potential targets for
      specific immunotherapy and are frequently expressed in bladder cancer. We studied
      the coordinated expression of a bladder cancer-associated CEA glycoform and of
      the mucins MUC1, MUC2 and MAUB under various growth conditions in the MGH-U3
      bladder-cancer cell line. CEA and MUC2 mRNAs and proteins were detected in nude
      mouse tumors and spheroids but not in monolayer cultures. Expression of MAUB and
      bladder-cancer CEA also was induced according to spatial configuration of cells.
      MUC1 was always expressed under various growth conditions, but its glycosylation
      was modulated: in spheroids and mostly in tumor cells, the SM3 protein epitope
      was unmasked and sialyl-Tn was induced. The kinetics of modulation of MAUB and
      bladder-cancer CEA were different. The epitope recognized by the monoclonal
      antibody (MAb) 19A211 was rapidly induced in the aggregation phase of spheroid
      formation and rapidly lost upon plating of tumor cells, suggesting a relationship
      with cell contact. By contrast, MAUB induction in spheroids was delayed to the
      compaction phase, when cell aggregates become resistant to disruption, and loss
      of expression upon tumor plating occurred slowly over several culture passages.
      No induction of these 2 antigens was observed in the presence of differentiation
      agents, endothelial cell products or interferon-gamma, but it occurred when MGH
      U3 cells were cultured at high density on extracellular matrix. Our results
      suggest that CEA and mucin antigen expression in bladder cancer is modulated by
      the spatial configuration of cells.

PMID- 9185703
TI  - Human pancreatic cancer cells (MPanc-96) recognized by autologous tumor
      infiltrating lymphocytes after in vitro as well as in vivo tumor expansion.
AB  - A human tumor line designated MPanc-96 has been established from a poorly
      differentiated primary pancreatic adenocarcinoma. MPanc-96 has a doubling time of
      27 hr and grows as a confluent monolayer in various culture media. Cytogenetic
      analysis of in vitro-cultured tumor cells revealed a large number of clonal
      chromosomal aberrations, confirming their neoplastic origin. MPanc-96 grows in
      SCID mice when injected s.c. Xenografts established from the tumor line had a
      similar histology as the primary tumor. Tumor-infiltrating lymphocytes (TILs)
      were isolated from the primary tumor, and cytotoxic T lymphocytes (CTLs) were
      generated after activation on immobilized anti-CD3 monoclonal antibody (MAb) for
      48 hr, expansion in low-dose IL-2 and repeated stimulation with irradiated MPanc
      96 tumor cells. The generated CTLs lysed fresh autologous tumor cells as well as
      in vitro and in vivo expanded tumor cells from passages 9-53, suggesting that one
      or more tumor-associated antigens (TAAs) are stably expressed. CTLs lysed tumor
      cells in an HLA-class I-restricted fashion but showed no significant cytotoxicity
      against autologous fibroblasts, several allogeneic pancreatic cancer cell lines
      or K562. Our findings may be significant for the design of an animal model for
      studying the mechanisms of immunotherapy in human pancreatic cancer or for the
      identification of TAAs in pancreatic cancer.

PMID- 9185704
TI  - Targeting BCL1 lymphoma with anti-idiotype antibodies: biodistribution kinetics
      of directly labeled antibodies and bispecific antibody-targeted bivalent haptens.
AB  - The mouse BCL1 lymphoma model has been used for evaluating immunotherapy with
      anti-idiotype (anti-Id) antibodies, including Id immunisation, IgG therapy and
      bispecific (Bs) antibody-targeted cytotoxicity. Here, we provide quantitative
      data on the targeting of small (25 +/- 12 mg) intrasplenic BCL1 tumours, using
      anti-Id IgG, F(ab')2 and anti-Id x anti-hapten BsF(ab')2 covalently labelled with
      125iodine, as well as noncovalent complexes of BsF(ab')2 and 125I-labelled
      bivalent hapten. The results are the following: 1) up to 115% of the injected
      dose per gram (% ID/g) of spleen can be localised in the first hour,
      corresponding to approximately 600% ID/g of tumour; 2) localisation is specific
      for cell-surface Id; 3) optimal doses can overcome circulating Id; 4) circulating
      Id markedly increases the catabolism of IgG, thus impairing tumour localisation;
      5) bivalent reagents are internalised by the target cells; 6) iodine covalently
      bound to bivalent antibodies [IgG, F(ab')2] is rapidly (T(1/2): 6-9 hr) released
      from the tumour; in contrast, the bivalent hapten is retained for a longer time
      (T(1/2): 25 hr); and 7) in the absence of bivalent hapten, the monovalent
      BsF(ab')2 is not rapidly internalised and dissociates from tumour cell-surface
      Id. Our results suggest that monovalent anti-Id, lacking Fc, can efficiently be
      targeted to the BCL1 tumour surface. For radioimmunotherapy, the intracellular
      targeting of catabolism-resistant 125I-labelled bivalent hapten provides optimal
      tissue selectivity.

PMID- 9185705
TI  - New EGF-R selective tyrosine kinase inhibitor reveals variable growth responses
      in prostate carcinoma cell lines PC-3 and DU-145.
AB  - The effect of an EGF-R selective tyrosine kinase inhibitor ZM252868 was evaluated
      on the proliferation of PC-3 and DU-145 prostate cancer cell lines, which are
      purported to utilize an EGF-R-mediated autocrine pathway for regulation of cell
      growth. Basal growth of DU-145 cells was inhibited in a dose-dependent manner by
      the inhibitor, showing a 70% reduction at 1 microM, whilst the growth of PC-3
      cells was not affected at this concentration. In the presence of 0.1 microM
      inhibitor, EGF and TGF alpha-stimulated DU-145 cell growth was decreased to below
      basal levels, while only TGF alpha-stimulated PC-3 cell growth was inhibited at a
      1-microM concentration. Any growth responses to aFGF, bFGF, KGF, IGF1 and PDGF by
      DU-145 and PC-3 cells were unaffected by the inhibitor at concentrations of 1
      microM or less. Additionally, the distribution of immunoreactive EGF-R varied
      between DU-145 and PC-3 cells, with EGF-R being predominately located on the cell
      membrane and in the cytoplasm, respectively.

PMID- 9185706
TI  - Characterization of 10 new monoclonal antibodies against prostate-specific
      antigen by analysis of affinity, specificity and function in sandwich assays.
AB  - While prostate-specific antigen (PSA) is already an invaluable marker for
      prostate cancer, there is continuing demand for new anti-PSA antibodies with
      specific characteristics, e.g., high sensitivity and specificity and equimolar
      binding to free PSA (f-PSA) and the PSA-alpha-1-antichymotrypsin complex (PSA
      ACT), as well as the ability to distinguish between these 2 immunoreactive forms
      of PSA. We have therefore generated and characterized 10 anti-PSA monoclonal
      antibodies (MAbs). Apparent dissociation constants (Kd) of MAbs were determined
      by direct ELISA yielding Kd-0.2-164.0 nM. Western blots suggested that 3 of the
      MAbs (60-1A2, 60-8A2 and 17-1A2) bind to linear epitopes. Sandwich assays
      identified 5 major antigenic regions as binding targets of the MAbs. Three
      combinations of MAbs recognize f-PSA and PSA-ACT in equimolar fashion with high
      sensitivity. Two of the MAb combinations are specific for f-PSA. Physical
      analysis of the new antibodies has allowed us to assign the MAbs to binding
      classes (based on their sandwiching capabilities) and to determine accurate
      apparent dissociation constants.

PMID- 9185707
TI  - Human beta2-adrenergic receptor/GS alpha fusion protein, expressed in 2 ras
      dependent murine carcinoma cell lines, prevents tumor growth in syngeneic mice.
AB  - We report a strategy of tumor growth inhibition based on the expression of a
      foreign protein with both potential anti-proliferative and immunogenic
      properties. To validate our approach, we used 2 ras-mutated murine carcinoma cell
      lines (carB and C57/PDV) transfected with the gene encoding a fusion protein
      containing the human beta2-adrenergic receptor and the alpha subunit of the Gs
      protein (beta2Gs). We previously showed that the sustained activation of the
      beta2Gs fusion protein expressed in carB cells (carB beta2Gs cells) induced a
      cAMP-dependent inhibition of cell growth in vitro. Here, we observed inhibition
      of tumor growth after s.c. inoculation of 2 carB beta2Gs clones (10C2 and 20F4)
      in syngeneic ICFW mice. We thus selected 3 C57/PDV beta2Gs clones (2D3, 5F3 and
      1G1) in which activation of the fusion protein was not efficiently coupled to the
      cAMP-PKA signaling pathway. Contrasting with carB beta2Gs clones, activation of
      the fusion protein in these C57/PDV beta2Gs clones did not have any anti
      proliferative effect in vitro. Therefore, they were good candidates to assess the
      immunogenic property of the fusion protein. Accordingly, none of the C57/PDV
      beta2Gs clones formed tumors in immunocompetent syngeneic C57BL/6 mice, while
      they were still tumorigenic in nude mice. Most interestingly, all of the beta2Gs
      clones that did not form tumors, from both cell lines, provided protection
      against respective wild-type tumor development. Our results show that expression
      of the beta2Gs fusion protein in cancer cells elicits inhibition of cell
      proliferation and/or immune rejection of both beta2Gs-modified and wild-type
      tumor cells.

PMID- 9185708
TI  - Identification of highly expressed genes in metastasis-suppressed chromosome
      6/human malignant melanoma hybrid cells using subtractive hybridization and
      differential display.
AB  - Microcell-mediated transfer of chromosome 6 into human melanoma cell lines C8161
      and MelJuSo suppresses metastasis by at least 95% without affecting
      tumorigenicity. Subtractive hybridization and differential display were used to
      identify the molecule(s) responsible for suppressing metastasis in neo6/melanoma
      (neo6/C8161 and neo6/MelJuSo) hybrids. Seven cDNA clones exhibiting
      quantitatively or qualitatively higher expression in neo6/melanoma hybrids were
      obtained. These genes fell into 2 categories: 1) transcription-related genes (AP
      2A, HMG-I(Y) and a novel isoform of nucleophosmin B23), which have previously
      been shown to regulate metastasis-associated genes; and 2) novel genes. One of
      the novel genes, designated KiSS-1, significantly suppressed metastasis of the
      human malignant melanoma cell lines MelJuSo and a highly metastatic subclone of
      C8161, C8161cl.9, following transfection and constitutive expression. Our results
      illustrate the power of subtractive hybridization and differential display to
      identify functional metastasis-controlling genes in human melanoma.

PMID- 9185709
TI  - Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N
      nitrosomorpholine.
AB  - The effects of ethyl alcohol (EtOH) during or after treatment with N
      nitrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylase (ODC)
      activity and the labeling index of the liver were investigated in male Sprague
      Dawley rats. Rats were given drinking water containing NNM for 8 weeks and
      received i.p. injections of 1 g EtOH/kg body weight every other day during or
      after treatment with NNM. Pre-neoplastic and neoplastic lesions staining
      positively for glutathione-S-transferase, placental type (GST-P), were examined
      immunohistochemically. At the end of experiment at week 16, administration of
      EtOH after NNM treatment had no significant effect on the number and size of GST
      P-positive hepatic lesions, whereas administration of EtOH during NNM treatment
      significantly increased the number and percentage area but not the mean area of
      GST-P-positive hepatic lesions. EtOH caused significant increases in the ODC
      activity of the liver and in the labeling indices of enzyme-altered lesions and
      the adjacent hepatocytes after the cessation of EtOH administration but not
      during EtOH treatment. Our findings indicate that EtOH enhances
      hepatocarcinogenesis and suggest that this effect may be closely related to the
      increases in ODC activity and cell proliferation in enzyme-altered lesions and
      the adjacent liver after EtOH treatment.

PMID- 9185710
TI  - Expression and function of the complement membrane attack complex inhibitor
      protectin (CD59) in human prostate cancer.
AB  - Protectin (CD59) inhibits homologous complement-mediated cytolysis by preventing
      formation of the membrane attack complex at the point of insertion and
      polymerization of C9 into cell membranes. The present study investigated the
      expression and function of CD59 on human prostatic tumor cells in situ and on 5
      human prostate cell lines in vitro originating from either metastatic tumors or
      benign prostate hypertrophy epithelial cells. Immunohistochemical staining of
      prostate carcinoma tissue with monoclonal antibody (MAb) MEM43 revealed weak to
      moderately strong expression of CD59 by prostate glandular epithelial cells. Flow
      cytometry with MEM43 demonstrated that the 5 prostate cell lines expressed
      different relative quantities of CD59. Indirect immunofluorescence analysis
      revealed uniform membrane staining of DU145 and PC3 cell lines with no membranous
      granularity in the staining pattern. Western immunoblots with MAb BRIC 229 showed
      that PC3 and DU145 cells express CD59 with a m.w. of 18-25 kDa. Treatment of DU
      145 and PC3 cells with phosphatidylinositol-specific phospholipase C caused a
      significant decrease of CD59 expression indicating that the CD59 expressed by
      prostate cancer cells is anchored to the cell membrane via a
      glycosylphosphatidylinositol (GPI) linkage. PC3 and DU145 cells were completely
      resistant to human complement-mediated cytolysis but became sensitive to killing
      in the presence of the CD59-neutralizing MAb YTH53.1. We conclude that malignant
      and benign human prostate cells express CD59 that is GPI-linked to the cell
      surface and that CD59 may regulate the immunological response to cancerous
      prostate cells by protecting the cells from the cytolytic activity of complement.

PMID- 9185711
TI  - In situ detection of PCR-amplified metalloproteinase cDNAs, their inhibitors and
      human papillomavirus transcripts in cervical carcinoma cell lines.
AB  - This study determined whether transcription of matrix metalloproteinase (MMP)-9
      and MMP-2, or tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, or
      human papillomavirus (HPV) open reading frames (ORFs) is associated with invasive
      behavior in cervical carcinoma cells. Transforming growth factor beta1 (TGF)
      treatment, which significantly increased the invasive behavior of Caski cells in
      Matrigel when compared with treatment with epidermal growth factor, was
      associated with a significant increase in the percentage of cells with MMP-9 and 
      2 mRNA as determined by RT in situ PCR. RT in situ PCR was then used to compare
      directly the expression of cells invading the Matrigel with the non-invasive
      cells. There was a significant increase in the percentage of HeLa cells invading
      the Matrigel expressing MMP-9 (33%) and MMP-2 (48%) when compared with the non
      invasive cells (11% and 12%, respectively); there was no significant change in
      the percentage of cells expressing either TIMP or HPV E6 or E7 RNA. Our data
      suggest that MMP-9 and -2 expression, but not TIMP or HPV expression, is an
      essential factor in the early stage of cervical cancer invasion.

PMID- 9185712
TI  - Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in
      metastatic melanoma.
AB  - Protein tyrosine kinases (PTKs) have been implicated in the development of many
      common human tumours including melanoma. Previously we isolated PTK gene
      sequences expressed in normal melanocytes. Here we examined expression of 9 of
      these genes in cell lines derived from defined stages of melanoma progression, by
      Northern blotting and in some cases immunoblotting. We also tested cells from 2
      animal models of particular stages in progression, as well as uncultured biopsies
      of metastatic melanoma. The expression of 2 receptor kinase family members found
      in melanocytes, PTK7/CCK-4 and SEK/TYRO1, was decreased or lost in advanced
      melanomas. PTK7 mRNA was found in only 54% of melanoma cell lines and 20% of
      melanoma biopsies. Similarly, expression was lost in 2 advanced cell lines
      selected from an early melanoma line that did express PTK7 mRNA. SEK/TYRO1
      expression was observed in 75% and 17% of cell lines from primary and metastastic
      melanomas, respectively. Conversely, mRNA for the non-receptor kinase PTK6/BRK
      was not detected in normal melanocytes or primary melanoma lines, but was found
      in 9% of metastatic melanoma cell lines.

PMID- 9185713
TI  - Autocrine interleukin-1 receptor antagonist can support malignant growth of
      glioblastoma by blocking growth-inhibiting autocrine loop of interleukin-1.
AB  - In situ hybridization (ISH) of human glioblastoma tissue sections revealed
      expression of interleukin-1 (IL-1)alpha and/or beta and IL-1 receptor types I and
      II (IL-1R I and II) in the majority of cases evaluable. To understand the
      function of IL-1-family members in human glioblastomas, we have studied 6
      glioblastoma cell lines. RT-PCR, ISH, ELISA and 125I-IL-1-binding assays revealed
      expression of IL-1 and high-affinity receptors for human (h)IL-1 in all but 1
      cell line. Using a colony growth assay in semi-solid media for testing serial
      plating efficacy (PE, number of colonies per number of cells seeded in %), only
      the IL-1R-negative cell line was not influenced by recombinant human (rh)IL
      1alpha or -beta, whereas IL-1 down-regulated the self-renewal of clonogenic cells
      of the other glioblastomas. Tritiated thymidine uptake was down-regulated by rhIL
      1 in all cell lines studied. Cell viability remained unchanged by rhIL-1.
      Wherever growth modulation by rhIL-1 was detected, it could be reversed by either
      soluble IL-1R I or II or by rhIL-1 receptor antagonist (ra). IL-1ra not only was
      able to reverse rhIL-1-induced growth modulation but alone could modulate
      glioblastoma growth in comparison with control in cell lines producing IL-1. Our
      results show the presence of public autocrine loops for IL-1 leading to growth
      inhibition in some glioblastomas. To understand these loops, we have studied
      expression and function of IL-1ra in glioblastomas. ISH of human glioblastoma
      tissue sections revealed expression of hIL-1ra in all 8 cases evaluable. In 4 of
      6 cell lines, IL-1ra was found in the supernatant under constitutive conditions,
      the IL-1R-negative line being among the 2 non-producers. The other non-producing
      cell line, HTB 17, showed expression of hIL-1R II. Most interestingly, a
      neutralizing antibody against IL-1ra down-regulated growth of IL-1- and IL-1ra
      producing glioblastoma cells to approx. 30% of the controls. Thus, public
      autocrine loops for IL-1 in human glioblastomas exist and result in growth
      inhibition. An autocrine production of IL-1-antagonizing molecules such as IL-1ra
      by these tumors can counteract this IL-1 function and represent a basic escape
      mechanism supporting malignant growth in some glioblastomas.

PMID- 9185714
TI  - A lymphocyte cell surface heat shock protein homologous to the endoplasmic
      reticulum chaperone, immunoglobulin heavy chain binding protein BIP.
AB  - BE2 is a cell surface monomeric 78-kDa protein (BE2-78) expressed on the
      malignant lymphocytes of cutaneous T-cell lymphoma and adult T-cell leukemia, on
      some lymphocytes from patients with acquired immunodeficiency syndrome and on
      Epstein-Barr virus-transformed B cells. BE2-78 positivity of cutaneous T-cell
      lymphoma tumor cells is a useful diagnostic and prognostic determinant in
      evaluating patients with that disorder. The BE2-78 protein was isolated from
      Epstein Barr virus-transformed B cells, purified by 1- and 2-dimensional
      electrophoresis and then sequenced. The sequence of 4 isolated peptide fragments
      was highly homologous with the 78-kDa heat shock protein, BiP, an endoplasmic
      reticulum chaperone. The similarity between BiP and BE2-78 was supported by the
      demonstration that BE2-78, like BiP, avidly binds to ATP. However, polyclonal and
      monoclonal reagents that recognize cytoplasmic 70- and 78-kDa heat shock proteins
      do not detect the BE2-78 antigen on the cell surface of cutaneous T-cell lymphoma
      or Epstein Barr virus-transformed lymphocytes, and peptide mapping demonstrates
      sequence divergence, suggesting that either they are distinct or conformationally
      different molecules. Our results indicate that BE2-78 is a cell surface heat
      shock protein. The possibility that malignant or transformed lymphocytes may
      express cell surface molecules with the capacity to bind a spectrum of exogenous
      or endogenous peptides has potential implications for tumor immunology.

PMID- 9185715
TI  - Decreased expression of ICAM-1 and its induction by tumor necrosis factor on
      breast-cancer cells in vitro.
AB  - In order to study adhesion-molecule expression and its consequences for cellular
      recognition, the presence of adhesion molecules ICAM-1, VCAM-1, VLA-4, LFA-1,
      alpha, LFA-1 beta, LFA-3, beta1-integrin and beta3-integrin was studied on
      specimens from breast tissue by immunohistochemistry and on cells from breast
      cell lines propagated in vitro. Breast-cancer tissue and the breast-cancer cell
      lines MCF-7, SK-BR-3 and ZR-75-1 showed expression of ICAM-1 and VLA-4
      significantly lower than that of benign breast cells or normal breast epithelium.
      Of various cytokines tested, including recombinant human (rh) interleukin-6 (IL
      6), rh tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2),
      granulocyte/macrophage-colony-stimulating-factor (GM-CSF), interferon-alpha (IFN
      alpha) and interferon-gamma (IFN-gamma), only TNF was able to re-induce
      expression of ICAM-1 on cells from MCF-7, SK-BR-3 and ZR-75-1. Further, the
      ability of either unstimulated or lymphokine-stimulated killer (LAK) cells to
      recognize and lyse native or TNF-stimulated breast-cancer cells was studied.
      Whereas neither unstimulated lymphocytes or LAK cells were able to lyse untreated
      breast-cancer cells deficient for ICAM-1 expression, pre-treatment of tumor cells
      with TNF led to increased tumor-cell lysis. Anti-ICAM-1 antibodies, and pre
      treatment of tumor cells with anti-TNF-receptor antibodies, abrogated these
      findings, corroborating their specificity. We thus conclude that the defective
      expression of ICAM-1 in our model might constitute a mechanism by which breast
      cancer cells escape immunologic recognition and lysis by appropriate effector
      cells.

PMID- 9185716
TI  - B7-1-transfected tumor vaccine counteracts chemotherapy-induced immunosuppression
      and prolongs the survival of rats bearing highly metastatic osteosarcoma cells.
AB  - To investigate the therapeutic efficacy of B7-1-expressing tumor vaccine on
      metastatic osteosarcoma, we introduced mouse B7-1 cDNA into a rat osteosarcoma
      cell line, MSK-8G. Flow cytometric analysis confirmed that the transfectants
      designated as B7-1-8G 10-1 and B7-1-8G 15-5 stably expressed B7-1 molecules on
      the cell surface. B7-1 transfectants were not only rejected by immunocompetent
      F344 rats but also conferred systemic immunity that protected against challenge
      with B7-negative parental osteosarcoma cells. In contrast, T-cell-deficient nude
      rats failed to reject B7-1 transfectants, indicating that T cells play a major
      role in the development of systemic immunity. We then conducted experimental
      therapies using irradiated B7-1-transfected tumor vaccine and methotrexate in an
      orthotopic implantation model. B7-1-transfected tumor vaccine significantly
      reduced the number of pulmonary metastatic nodules. Moreover, the combination of
      methotrexate and tumor vaccine further decreased the number of pulmonary
      metastatic nodules. Most important, the combined therapy with methotrexate and
      tumor vaccine resulted in a tumor-free condition as judged by the
      histopathological absence of tumors and survival of rats for more than 180 days.
      Furthermore, B7-1-transfected tumor vaccine could counteract the
      immunosuppressive effect of methotrexate. These findings strongly suggest that
      the B7-1-transfected tumor vaccine may be of clinical value for patients with
      metastatic osteosarcoma who exhibit immunosuppression due to chemotherapy.

PMID- 9185718
TI  - Growth inhibition of transplantable mouse tumors by non-digestible carbohydrates.
AB  - The possible influence of dietary non-digestible carbohydrates (15%
      oligofructose, inulin or pectin incorporated in basal diet) on the growth of
      intramuscularily transplanted mouse tumors, from 2 tumor lines (TLT and EMT6),
      was investigated. The results were evaluated by regular tumor measurements with
      Vernier caliper. Mean tumor surface in experimental groups was compared with that
      in animals of control group fed basal diet containing starch as the only
      carbohydrate. The growth of both tumor lines was significantly inhibited by
      supplementation of non-digestible carbohydrates.

PMID- 9185717
TI  - Natural interferon-alpha activity in hormone-sensitive, hormone-resistant and
      autonomous human breast-cancer cell lines.
AB  - This study explored the activity of natural interferon-alpha (nIFN-alpha) in
      regulating cell growth of 6 breast-cancer cell lines. The anti-proliferative
      effect of the combination nIFN-alpha and tamoxifen (TAM) or medroxyprogesterone
      acetate (MPA) in CG-5 estrogen-sensitive mammary cancer cells was investigated,
      and the ability of nIFN-alpha to restore hormone-sensitivity in the MPA-resistant
      MCF-7 SK sub-line was examined. nIFN-alpha, at concentrations ranging from 10 to
      1000 IU/ml, inhibited cell proliferation of all cell lines tested after 3 and 6
      days of treatment. In particular, the highest concentration of the drug used was
      equally effective in hormone-sensitive and in hormone-insensitive cells. A 6-day
      pretreatment of CG-5 cells with nIFN-alpha, at the above-mentioned doses,
      sensitized them to the growth-inhibiting activity of subsequent exposure to 10(
      7) M TAM or MPA, which resulted in a synergistic effect, and could be explained
      on the basis of the observed enhancement of estrogen and progesterone receptors
      due to IFN activity. Conversely, the simultaneous drug combination did not modify
      the response to the hormone in CG-5 cells. Pre-treatment with nIFN-alpha (from 10
      to 1000 IU/ml) restored MPA sensitivity in the MCF-7 SK sub-line, but no
      modulation of progesterone receptors was seen in this model. The hormone
      sensitivity of the parental cell line was not substantially affected by pre
      exposure to nIFN-alpha. These data indicate that nIFN-alpha may be potentially
      useful in enhancing the clinical effectiveness of TAM and MPA and in overcoming
      hormone resistance.

PMID- 9185719
TI  - Hepatitis-C-virus infection and cancer.

PMID- 9185720
TI  - Wild-type DNA sequence of the N-myc transactivation domain in human
      neuroblastoma.

PMID- 9185721
TI  - Infrequent allelic imbalance at the major susceptibility HPC1 locus in sporadic
      prostate tumours.

PMID- 9185722
TI  - High expression of MAGE-3 protein in squamous-cell lung carcinoma.

PMID- 9185723
TI  - Analysis of voice changes after thyroplasty using linear predictive coding.
AB  - Objective measurement of vocal quality is difficult in patients with severe voice
      disorders. Improved success has been reported using a modeling technique known as
      linear predictive coding. This technique uses an inverse filter to estimate a
      glottic excitation signal. The pitch amplitude is defined as the height of the
      first peak of the autocorrelation of the glottic excitation signal. In this study
      linear predictive coding was used to analyze voice disorders in patients with
      vocal fold immobility. Voice recordings were made in 16 patients undergoing vocal
      fold medialization and 10 patients who had no surgical procedure between
      measurements. The voice quality was rated by three speech pathologists. Five
      acoustic parameters were calculated from the samples. The best agreement with the
      listeners' perceptual analysis was achieved using the pitch amplitude. Both pitch
      amplitude and the perceptual ratings of voice quality improved in patients
      undergoing vocal fold medialization. Therefore the linear model of speech
      production and inverse filtering are useful in measuring vocal quality in
      patients with vocal fold immobility.

PMID- 9185724
TI  - Contemporary management of the aging brow and forehead.
AB  - Management of the aging brow and forehead has recently evolved based on available
      innovative technologies. Likewise, procedure-specific indications have changed
      based on collective surgical experiences. No longer is the approach based solely
      on hair pattern or degree of brow ptosis. Patients require varying combinations
      of brow elevation (prior to blepharoplasty), correction of brow asymmetries, and
      hairline-preserving forehead elevation. Some may only require excisional or
      paralytic procedures of the frontalis muscle (horizontal forehead creases),
      corrugator supercilii muscles (vertical glabellar furrows), and procerus muscle
      (horizontal glabellar furrows). We present a 3-year experience using a problem
      specific approach. This incorporates endoscopic technology, botulinum toxin type
      A purified neurotoxin complex (Botox, Allergan, Irvine, CA) intramuscular
      injection, and traditional procedures such as the coronal, pretrichial,
      midforehead, and direct browlift. Current indications, patient selection, and
      results are also discussed.

PMID- 9185725
TI  - Resorbable fixation plates in head and neck surgery.
AB  - A skeletal fixation system employing plates made of polylactic and polyglycolic
      acid has been employed at Indiana University Medical Center since July 1993 in
      105 craniofacial reconstructions, 45 cases of maxillofacial trauma, 10 craniotomy
      flap repairs, and five cases involving reconstruction of the laryngotrachea.
      Because these plates eventually resorb, they offer significant theoretical
      advantages. No inhibition of structural growth should occur when using this
      system in children. Tissue tolerance of these plates has been excellent. The
      technical details of using heat to allow reshaping of the plates as well as the
      methods of fixation of the plates are discussed.

PMID- 9185726
TI  - Surgical outcome in 87 patients with Zenker's diverticulum.
AB  - Surgical treatment of Zenker's diverticulum is controversial because many
      different procedures exist. We retrospectively reviewed 87 consecutive patients
      surgically treated for Zenker's diverticulum at a tertiary care institution from
      1976 through 1993. Four surgical procedures were performed: cricopharyngeal
      myotomy alone (n = 16), excision (hand-sewn) plus myotomy (n = 51), excision
      (stapler) plus myotomy (n = 11), and diverticulopexy plus myotomy (n = 9). There
      were three surgical mortalities (3.5%) and a complication rate of 24%. Eighty
      patients (92%) were available for follow up. Sixty-eight patients (78%) reported
      excellent relief of symptoms, 10 (13%) reported improvement with occasional
      symptoms, and two (3%) described persistent dysphagia. No statistical difference
      in complication rate was found among surgical groups (P = 0.15). Myotomy alone
      patients had worse outcomes (P = 0.04) compared with the other surgical groups.
      Median follow-up was 7.5 months.

PMID- 9185727
TI  - A cost-effective and rational surgical approach to patients with snoring, upper
      airway resistance syndrome, or obstructive sleep apnea syndrome.
AB  - The past decade has seen several innovations in the surgical techniques available
      for treatment of patients with sleep-disordered breathing. Outpatient techniques
      such as laser-assisted uvulopalatoplasty (LAUP) and more aggressive procedures
      designed to address hypopharyngeal and base of tongue obstruction (genioglossus
      advancement and hyoid myotomy) have been developed and proven successful. We
      describe the efficacy of LAUP for snoring (72.7%), upper airway resistance
      syndrome (81.8%), and mild (mean [+/-SD] respiratory disturbance index [RDI] = 12
      +/- 8.1) obstructive sleep apnea (41.7%) in 56 patients who underwent 132 LAUP
      procedures in a 26-month period. Thirty-two patients with more significant
      obstructive sleep apnea (mean RDI = 41.8 +/- 23.1) underwent multilevel
      pharyngeal surgery consisting of genioglossus advancement and hyoid myotomy
      combined with uvulopalatopharyngoplasty. The surgical success rate in this group
      of patients was 85.7% when commonly accepted criteria were applied. We recommend
      a stratified surgical approach to patients with sleep-disordered breathing.
      Progressively worse airway obstruction marked by multilevel pharyngeal collapse
      and more severe sleep-disordered breathing is treated with incrementally more
      aggressive surgery addressing multiple areas of the upper airway.

PMID- 9185728
TI  - Retropalatal airway characteristics in uvulopalatopharyngoplasty compared with
      transpalatal advancement pharyngoplasty.
AB  - Uvulopalatopharyngoplasty (UPPP) is reported successful in treatment of
      obstructive sleep apnea for approximately 50% of patients. Several modifications
      of the procedure have been described, including transpalatal advancement
      pharyngoplasty, which resects a portion of posterior hard palate and advances the
      soft palate anteriorly. Comparing effectiveness of different techniques based on
      sleep and respiratory data is confounded by multiple variables including clinical
      failure at nonsurgical sites and imprecise patient selection techniques. Since
      pharyngeal surgical procedures prevent collapse and obstruction by structurally
      modifying the upper airway, measuring structural changes in size and
      collapsibility provides a method to compare techniques. To evaluate whether
      transpalatal advancement pharyngoplasty is more effective in modifying upper
      airway characteristics than UPPP, upper airway cross-sectional size and
      collapsibility were measured after UPPP and transpalatal advancement
      pharyngoplasty. Six patients were evaluated using a quantitative endoscopic
      technique. After transpalatal advancement pharyngoplasty maximal retropalatal
      airway size increased 321% from 29.7 +/- 9.9 to 95.3 +/- 16 mm2 (P < 0.01), and
      retropalatal closing pressure decreased from 4.7 +/- 1.6 to -3.8 +/- 0.7 cm/H2O
      (P < 0.01) compared with UPPP. Respiratory disturbance index decreased from 74.5
      +/- 13.5 to 29.2 +/- 9 events/hour postoperatively (P < 0.05). Results support
      the conclusion that transpalatal advancement pharyngoplasty increases
      retropalatal size and decreases retropalatal collapsibility compared with UPPP.
      Since these characteristics are postulated to contribute to increased stability
      during sleep, transpalatal advancement pharyngoplasty may potentially improve
      UPPP outcome in selected patients with small retropalatal airway areas after
      traditional surgery.

PMID- 9185729
TI  - Head and neck manifestations of plasma cell neoplasms.
AB  - Multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma
      are plasma cell neoplasms. They represent distinct manifestations of a disease
      continuum, whereby the clinical findings are critical to diagnosis. Plasma cell
      neoplasms are histologically similar, and distinguishing one from the other has
      significant implications for treatment and survival. Plasma cell neoplasms are
      relatively unusual malignancies of the head and neck region. We present a case
      series of plasma cell neoplasms involving the skull base, paranasal sinus,
      larynx, and mandible as an introduction to a complete review of the literature on
      plasma cell neoplasms of the head and neck area.

PMID- 9185730
TI  - Sudden sensorineural hearing loss after general anesthesia for nonotologic
      surgery.
AB  - Sudden sensorineural hearing loss (SNHL) is a well-recognized phenomenon that is
      attributed to a variety of etiologies. Sudden SNHL after cardiopulmonary bypass
      surgery has been well reported and is thought to be due to microemboli. However,
      a review of the English literature revealed only 15 cases of SNHL after general
      anesthesia for nonotologic surgery. Several etiologies for this loss have been
      suggested, but no proven pathogenesis is yet available. This report adds to the
      literature three additional cases of sudden SNHL after general anesthesia for
      nonotologic surgery. The literature is reviewed and proposed mechanisms of injury
      are discussed.

PMID- 9185731
TI  - Utility of preoperative radionuclide scanning for primary hyperparathyroidism.
AB  - This study retrospectively reviews 60 cases of primary hyperparathyroidism, 21 of
      whom underwent technetium 99 sestamibi scanning and 10 of whom underwent thallium
      201/technetium 99 pertechnetate scanning preoperatively. The sestamibi and
      thallium scans demonstrated an 89.5% and a 62.5% sensitivity rate for adenoma,
      respectively. Neither scan demonstrated hyperplastic glands well. Although the
      scans localized adenomatous glands to the correct side well, the ability to
      localize them more discretely was 68.4% and 62.5%, respectively. In cases of
      solitary adenoma the effect of an accurate preoperative scan on operative time
      for bilateral exploration was not significant, whereas the experience of the
      attending surgeon was significant. Also, the cost of the scans at our institution
      was greater than the cost of the time saved in performing even unilateral neck
      exploration. Thus preoperative radionuclide scanning is not cost-effective for
      the initial exploration of patients with primary hyperparathyroidism and is
      insufficiently sensitive to make routine unilateral neck exploration for adenoma
      consistently effective.

PMID- 9185732
TI  - Efficacy and cost-effectiveness of multihole fine-needle aspiration of head and
      neck masses.
AB  - To determine whether the specimen from fine-needle aspiration (FNA) biopsy of
      head and neck masses has greater diagnostic accuracy when using multihole needles
      than when using conventional, single-hole needles, we did a prospective,
      randomized, single-blinded study comparing diagnoses obtained using both types of
      needles in FNA biopsies of head and neck masses. Eighty-eight patients served as
      their own controls and had 91 FNA biopsies with both multihole and single-hole,
      22-gauge needles. Order of biopsy was randomized and was unknown to the
      cytopathologist. No statistically significant differences were noted in quantity
      of specimen material obtained, quality of fixation, or diagnostic value between
      the multihole and conventional needle. We found no advantage in using the more
      costly multihole needle in FNA biopsy of head and neck masses.

PMID- 9185733
TI  - Genetic susceptibility to head and neck cancer: interaction between nutrition and
      mutagen sensitivity.
AB  - The development of head and neck cancer may depend not only on exposure to
      environmental carcinogens but also on a genetically based susceptibility to
      carcinogen-induced damage. This thesis presents a case-control study that
      demonstrates the significance of mutagen sensitivity, a measure of an
      individual's intrinsic DNA repair capacity against free radical damage, as a risk
      factor for the disease. As part of the case-control analysis, 167 previously
      untreated patients and 177 age- and sex-matched healthy controls were assessed
      for various lifestyle factors including tobacco and alcohol habits, occupational
      exposures, and diet. Mutagen sensitivity expressed by each individual was
      determined by quantifying bleomycin-induced chromosomal breaks within peripheral
      blood lymphocytes in vitro. Consistent with our initial observations and those of
      others, mutagen hypersensitivity was strongly associated with increased risk of
      head and neck cancer (odds ratio, 4.95; 95% confidence interval, 2.67 to 9.17)
      after adjusting for age, sex, and race. Low intake of vitamins C and E was also
      associated with an increased risk of disease and was interactive with mutagen
      sensitivity in risk estimates. Individuals with both a low intake of various
      antioxidants and increased chromosomal sensitivity to oxidant-induced DNA damage
      were at greatest risk. This study supports the concept that the risk of head and
      neck cancer is determined by a balance of factors that either enhance or protect
      against free radical oxygen damage, including innate capacities for DNA repair.

PMID- 9185734
TI  - Correlation between vocal functions and glottal measurements in patients with
      unilateral vocal fold paralysis.
AB  - Observations and analysis of glottal characteristics are critical in choosing the
      best modality for surgery in patients with unilateral vocal fold paralysis (UVP).
      This study suggests that multiple glottal characteristics influence the vocal
      product in patients with UVP. In addition to the horizontal position of the
      paralyzed vocal fold (deviation from the midline), the glottal area, degree of
      bowing of the paralyzed and contralateral vocal folds, maximum separation between
      vocal folds, compensatory glottal maneuvers, and the vertical glottic closure
      plane significantly influenced the quality of the voice. Clinicians should be
      aware of these observations to facilitate treatment planning and assessment of
      the results of surgical procedures used to improve voice quality in cases of UVP.

PMID- 9185735
TI  - Malformation and stenosis of the cricoid cartilage in association with Larsen's
      syndrome.
AB  - Three patients with the typical features of Larsen's syndrome are described. All
      three developed severe respiratory symptoms caused by a congenital subglottic
      stenosis. Tracheotomy and treatment of the stenosis by means of
      laryngotracheoplasty resulted in complete collapse of the cricoid cartilage and
      the proximal tracheal skeleton. Lack of rigidity of the laryngeal and tracheal
      cartilages in patients with Larsen's syndrome could well be responsible for this
      failure. Surgical treatment consisted of resection of the stenotic and collapsed
      areas and end-to-end anastomosis. This therapy was eventually successful in all
      three patients.

PMID- 9185736
TI  - Nasal dermoid sinus cysts in children.
AB  - Thirty-six children with nasal dermoid sinus cysts were treated in the Department
      Pediatric Otolaryngology, Armand Trousseau's Children's Hospital (Paris, France)
      between 1974 and 1994. Ten of the patients presented with a midline cyst only,
      eight had nasal pits only, and 18 had combined cases. In six of the 36 patients,
      presurgical imagery indicated signs of intracranial extension of the tract,
      reaching the foramen caecum without intracranial mass. Three surgical techniques
      were used: an external rhinoplasty approach with medial crura section in 23
      cases, a direct median approach in seven cases, and a paracanthal approach in six
      cases. Only two cases had meningeal adherences. Two superficial recurrences
      occurred within the 7-year follow-up period. Widening of the scar occurred in
      four children after verticomedian approach or nasal pit excision. The external
      rhinoplasty procedure with medial crura section results in a wide surgical
      approach, low recurrence rate, and good aesthetic results.

PMID- 9185737
TI  - Surgical experience with bone-anchored hearing aids in children.
AB  - Titanium osseointegrated implants for bone-anchored hearing aids (BAHAs) have
      been in use since 1977. A series of 32 children who received implantation since
      1990 is reported. The report focuses on the surgical aspects of BAHAs,
      predisposing factors, and prevention of complications in an unusual pediatric
      population. The records of 32 children who had undergone two-stage implantation
      of a BAHA were retrospectively reviewed. The majority of the patients had
      craniofacial abnormalities. Of the 32 implantees, 29 use their BAHA at present.
      Five children failed to achieve osseointegration, and eight patients have had
      revision surgery for lost abutments, trauma, or chronic skin problems. There were
      no differences between preimplantation and postimplantation bone or air
      conduction thresholds. The pediatric BAHA carries with it a unique set of
      challenges and problems but can be successfully implanted and maintained.

PMID- 9185738
TI  - Positional vertigo and ageotropic bidirectional nystagmus.
AB  - A strong paroxysmal positional horizontal nystagmus accompanied by symptoms
      similar to those of paroxysmal positional vertigo (PPV) can be observed in a
      small fraction of patients who have positional vertigo. This nystagmus may be a
      lateral canal variant of PPV. We evaluated nine patients who had episodes of
      prolonged, intense positional vertigo provoked by lateral movements of the head
      while in the supine position. The nystagmus appeared as horizontal and was
      directed toward the uppermost ear (ageotropic) when the head was rotated to
      either side (bidirectional). The duration of nystagmus lasted more than 1 minute
      in all the cases, although it presented a progressive decrease in the velocity of
      the slow component. The clinical and electronystagmographic features of this
      syndrome lead us to propose a different form of horizontal canal PPV associated
      with a paroxysmal positional ageotropic and bidirectional nystagmus, probably
      caused by a "heavy cupula" as a result of deposits of extraneous bodies
      (otolithic?) or by a cupula denser than the endolymph.

PMID- 9185739
TI  - An efficiency comparison of four heat and moisture exchangers used in the
      laryngectomized patient.
AB  - Bypassing the upper airway places the burden of humidification on the lower
      airway. For this reason passive heat and moisture exchangers (HMEs) are used in
      the laryngectomized patient in an attempt to minimize the effect of lost upper
      airway function. We measured efficiency and airflow resistance and calculated the
      costs of four HMEs used in the laryngectomized patient. The HMEs were measured
      according a modified International Standards Organization (ISO) 9360 standard.
      The airflow resistance was measured at flow rates of 15, 30, and 60 L/min. The
      measurements were repeated three times. Costs were calculated with two realistic
      scenarios. The study found that there are significant differences in moisture
      output and airflow resistance between the HMEs tested. There are major daily cost
      differences between these devices. This study shows that filter material and size
      influence the HME's moisture output efficiency and airflow resistance
      considerably. The construction differences and filter and housing type have great
      influence on the HME's daily costs. We believe that knowledge of the efficiency
      in combination with the average daily costs of the HMEs allows the clinician to
      make a balanced choice of which filter to use.

PMID- 9185740
TI  - Preoperative embolization in the management of neck paragangliomas.
AB  - Surgery of neck paragangliomas carries inherent risks of excessive blood loss and
      cranial nerve injury. Preoperative embolization has been used to lessen the
      morbidity of surgery. We sought to characterize our experience with preoperative
      embolization by evaluating safety, efficacy, and surgical data. During a period
      of 22 years (1974 to 1996), 19 consecutive patients with 27 histopathologically
      confirmed neck paragangliomas were surgically treated at the Oulu University
      Hospital. All patients underwent preoperative arteriography and 17 patients had
      cervical ultrasonography (US). Eleven patients with 15 tumors were operated on
      without embolization and nine patients with 12 tumors were preoperatively
      embolized with 150- to 250-microm polyvinyl alcohol (PVA) particles. The mean
      blood loss during surgery in the nonembolized group was 1374 mL (range, 100 to
      4500 mL) and the mean operation time was 4 hours and 48 minutes (range, 1.5 to 9
      hours). In the embolized group the mean blood loss was significantly less (588
      mL; range, 100 to 1800 mL; P = 0.04) and the mean operation time shorter (3 hours
      24 minutes; range, 2 to 5 hours; P = 0.05). No embolic complications were
      recorded after the embolization. We conclude that preoperative embolization of
      neck paragangliomas 3 cm or greater in diameter with PVA particles is safe.
      Embolization to minimize operative bleeding facilitates surgery, shortens the
      operation time, and lessens the surgical risks.

PMID- 9185741
TI  - Mutation of p53 in squamous cell cancer of the head and neck: relationship to
      tumor cell proliferation.
AB  - Rapid proliferation of squamous cell carcinomas of the head and neck (SCCHN)
      during therapy may contribute to treatment failure. We have investigated the
      presence of p53 abnormalities in patients with SCCHN as a correlate of
      proliferation rate and other pathologic and clinical variables. p53 Mutation, as
      determined by polymerase chain reaction and single-strand conformation
      polymorphism analysis of microdissected frozen sections of tumor biopsies, was
      significantly associated with a high labeling index, as determined by in vivo
      infusion of IUdR and BrdU (P = 0.017). p53 Protein expression was detected by
      immunohistochemistry with two different antibodies, followed by quantitative
      image analysis. Many cases exhibited strong p53 protein expression in the absence
      of mutations within the conserved region of the gene, and expression was not
      related to proliferation. The presence of p53 mutations was related to tumor
      differentiation in this group of patients.

PMID- 9185742
TI  - Three-dimensional image-guided endonasal surgery with a microdebrider.
AB  - We report the first intraoperative use of a microdebrider as a stereotactic three
      dimensional (3D) navigation instrument in paranasal and frontobasal surgery. The
      microdebrider uses rotating blades and an integrated suction device for
      controlled removal of tissue under video-endoscopic view. The ISG Viewing Wand
      uses the patient's computed tomography/magnetic resonance (CT/MR) data and a 3D
      reconstruction thereof and a high-precision position-sensitive mechanical arm for
      intraoperative three-dimensional navigation. We have linked the microdebrider to
      the Viewing Wand to transform it into a continuously available intraoperative
      stereotactic localizing device. We discuss the problems related to this extension
      of the Viewing Wand and demonstrate the practical use in an exemplary
      polypectomy.

PMID- 9185743
TI  - Ammonia and GABA-ergic neurotransmission: interrelated factors in the
      pathogenesis of hepatic encephalopathy.

PMID- 9185744
TI  - Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans.
AB  - This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a
      6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid
      secretion. Four cholecystectomized patients who had gallstones and an interrupted
      enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic
      and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h
      for 3 hours. In hourly bile samples collected for 8 hours after the beginning of
      the infusion, biliary bile acid composition (by high-performance liquid
      chromatography), biliary lipid concentrations (by standard methods), and
      distribution of biliary carriers (by gel chromatography) were evaluated. Blood
      liver function tests were performed before and after the infusions.
      Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary
      bile acids in all patients except for one infused with taurohyodeoxycholic acid.
      Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol
      and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451
      micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061
      micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids).
      The secretory ratio between phospholipid and cholesterol was significantly higher
      after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with
      taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment
      with taurohyodeoxycholic acid was positively related with percent concentration
      of phospholipids but not with that of cholesterol. The opposite trend was
      observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic
      acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was
      carried in a gel-chromatographic fraction corresponding to an apparent molecular
      weight of 80 to 200 kd. No alteration in liver function test results was observed
      after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid
      stimulates greater cholesterol and phospholipid secretion than
      tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory
      ratio. In bile enriched with both bile acids, biliary cholesterol is transported
      in non-micellar aggregates. Finally, in the conditions of our study,
      taurohyodeoxycholic acid was not hepatotoxic.

PMID- 9185745
TI  - Effect of ileal autotransplantation on cholesterol, bile acids, and biliary
      lipids in pigs with proximal small bowel resection.
AB  - Our major aim was to investigate the consequences of ileal autotransplantation in
      pigs with proximal small intestinal resection on biliary lipids and metabolism of
      bile acids. Biliary lipid secretion rates and bile acid absorption were assessed
      by measuring dietary and biliary lipids, fractional cholesterol absorption, and
      fecal excretion of cholesterol and bile acids. In addition, serum bile acids and
      cholesterol, biliary and fecal bile acid species, and ileal villus height were
      determined after resection of the proximal 75% of the jejunoileum (n = 15) and
      autotransplantation of the remaining ileum with systemic venous drainage (n = 15)
      or transection (n = 5). Autotransplantation further increased fecal excretion of
      neutral and acidic steroids and serum concentration of bile acids after proximal
      resection (P < .05 for all); autotransplantation significantly decreased serum
      cholesterol, ileal villus height, fractional bile acid and cholesterol
      absorption, and biliary molar percentage of total and primary bile acids, whereas
      biliary secretion of bile acids, enriched by secondary bile acids, and
      cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile
      acid and cholesterol absorption, biliary molar percentage of bile acids, and
      proportion of secondary biliary bile acids were altered by transplantation from
      the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/-
      3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/-
      1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation
      biliary bile acid secretion correlated positively with fractional reabsorption (r
      = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus
      height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary
      molar percentage of bile acids, increased biliary secondary bile acids, and short
      ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which
      with decreased absorptive area may contribute to malabsorption of other lipids
      after ileal autotransplantation. Compensatory increase in cholesterol synthesis
      in the pigs with autotransplanted ileum appeared sufficient for constant biliary
      secretion of cholesterol and bile acids.

PMID- 9185746
TI  - The low-dose monoethylglycinexylidide test: assessment of liver function with
      fewer side effects.
AB  - The hepatic metabolism of lidocaine (1 mg/kg intravenously) to its metabolite
      monoethylglycinexylidide (MEG-X) is the basis of the standard MEG-X test. To
      reduce the lidocaine-induced side effects, we evaluated the MEG-X formation after
      0.5 and 1 mg/kg lidocaine intravenously in subjects with normal (n = 5) and
      severely impaired liver function (n = 7) (study I). From this study, a low-dose
      test (MEG-X concentration 30 minutes after 50 mg lidocaine intravenously [MEG
      X30min] normalized to standard MEG-X test results) was developed. Sensory side
      effects from this low dose and from the standard MEG-X test were compared in a
      double-blind, randomized, cross-over study (study II) comprising 15 individuals
      with normal liver function and 45 patients with cirrhosis (15 Child A, 15 Child
      B, and 15 Child C). In study I, MEG-X formation rate was dose-independent in
      patients with severely impaired liver function. In study II, normalized MEG-X
      test results (ranging from < or = 4 to 120 microg/L) were virtually identical to
      the standard test results (mean difference: -1.9 microg/L; 95% confidence
      interval [CI]: -5.3; 1.5 microg/L). Fewer individuals experienced side effects
      (30% vs. 53%) with the low-dose test (P = .0013). In a multivariate analysis, the
      Child-Pugh score was inversely related to the occurrence of side effects. The low
      dose MEG-X test gives almost identical results to the standard MEG-X test and is
      associated with fewer side effects, which occur less often in individuals with
      more severely compromised liver function.

PMID- 9185747
TI  - Long-lasting NO overproduction in cirrhotic patients with spontaneous bacterial
      peritonitis.
AB  - Nitric oxide production was studied in cirrhotic patients with spontaneous
      bacterial peritonitis (SBP) or with other infections. We followed up on the time
      course of serum nitrate levels in 51 hospitalized patients aged between 34 and 81
      years. Four groups were defined: patients with SBP (group 1, n = 14), patients
      with bacteremia (group 2, n = 11), patients with urinary tract infection (group
      3, n = 11) and patients in a stable clinical condition (group 4, n = 20). The
      four groups did not differ in terms of Pugh score (11 +/- 1, 10 +/- 1, 11 +/- 1,
      and 10 +/- 1, respectively). Serum nitrate levels averaged 31 +/- 2 micromol/L in
      group 4 (84 samples). On the day results of cytobacteriological examination were
      positive, mean serum nitrate levels were 75 +/- 17, 63 +/- 9, and 36 +/- 9
      micromol/L, respectively, in groups 1 (17 cases), 2 (11 cases), and 3 (11 cases)
      (P < .001). The maximum nitrate values recorded during follow-up were higher in
      groups 1 (149 +/- 15 micromol/L) and 2 (112 +/- 11 micromol/L) than in group 3
      (66 +/- 7 micromol/L; P < .001 and < .01, respectively). These maximum values
      were recorded in all groups approximately 2 weeks after the infection was
      diagnosed. The mean duration of NO overproduction, as defined by nitrate level
      (3)90 micromol/L, was 15 +/- 3 days in group 1 and 5 +/- 1 day in group 2. When
      the nitrate concentration was studied in serum and ascitic fluid sampled on the
      same day, it was found to be higher in ascitic fluid than in serum in eight cases
      of SBP in the period preceding the peak serum nitrate concentration (100 +/- 17
      vs. 63 +/- 14 micromol/L; P < .001). Our data indicate that SBP in cirrhotic
      patients led to a long-lasting increased local production of NO. This
      overproduction may contribute to maintaining splanchnic vasodilation and thus
      worsen the hyperkinetic state in these patients.

PMID- 9185748
TI  - Influence of malnutrition on the prevalence of bacterial translocation and
      spontaneous bacterial peritonitis in experimental cirrhosis in rats.
AB  - Bacterial translocation (BT) has been involved in the pathogenesis of spontaneous
      bacterial peritonitis (SBP) in experimental cirrhosis. Because malnutrition is a
      common feature in cirrhosis, the aim of this study was to evaluate the effect of
      nutrition on BT and SBP. We induced cirrhosis in 44 Sprague-Dawley rats by
      administration of oral CCl4, and, afterward, 26 animals were maintained with
      dietary restriction. Cultures of mesenteric lymph nodes (MLN), peripheral and
      portal blood, liver, and spleen were performed. SBP occurred in 48% of the rats
      with ascites, this being more frequent in the malnourished animals (80%) than in
      control rats (29%). BT appeared in all the rats with SBP (100%) but only in 57%
      without it. In the malnourished animals, the BT rate was 95%, while it was 30% in
      the control group. These results suggest that malnutrition increases the BT rate
      and the risk of developing SBP in experimental cirrhosis, and that BT is frequent
      in cirrhosis and may play a role in the development of SBP.

PMID- 9185749
TI  - Impairment of renal function during moderate physical exercise in cirrhotic
      patients with ascites: relationship with the activity of neurohormonal systems.
AB  - Moderate physical exercise does not affect glomerular filtration rate (GFR) and
      renal excretory function in normal subjects. This study is aimed at assessing the
      effects of moderate physical exercise on renal function in 21 nonazotemic
      cirrhotic patients with ascites. Arterial pressure, heart rate, and renal
      function were assessed in the patients after 2 hours in the supine position and
      during 30 minutes of moderate cycloergometric exercise in the sitting position.
      The activity of the renin-aldosterone and sympathetic nervous systems and the
      plasma levels of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP)
      were determined at the end of each period. Physical exercise induced a marked
      reduction in GFR (75 +/- 10 to 49 +/- 6 mL/min), free-water clearance (6.1 +/- 1
      to 3.4 +/- 1 mL/min), and sodium excretion (7.8 +/- 2 to 4.3 +/- 1 microEq/min)
      in 10 patients (Group I). In the remaining 11 cases (Group II) there were no
      changes in these parameters. Renal perfusion significantly decreased in both
      groups although the reduction was greater in Group I (-34.7% +/- 4.6% vs. -7.5%
      +/- 3.1%, P < .001). Physical exercise was associated with a significant and
      comparable increase in arterial pressure, heart rate, and plasma levels of renin,
      aldosterone, and norepinephrine (NE) in the two groups of patients. The ANP
      concentration did not change. Patients from Groups I and II differed
      significantly (P < .05) only in plasma renin activity (PRA) and NE concentration,
      which were higher in Group I patients both in the supine rest (renin: 4.7 +/- 1.6
      vs. 1.4 +/- 0.5 ng/mL x h; NE: 576 +/- 115 vs. 288 +/- 42 pg/ mL) and during
      exercise (renin: 7.1 +/- 1.8 vs. 2.6 +/- 1 ng/ mL x h; NE: 925 +/- 135 vs. 630 +/
      90 pg/mL). In conclusion, moderate physical exercise has no detrimental effects
      on renal function in cirrhotic patients with ascites with no or mild activation
      of the renin-aldosterone and sympathetic nervous systems. However, moderate
      physical exercise causes a marked impairment in the renal function of patients
      with ascites with marked stimulation of these vasoconstrictor systems.

PMID- 9185750
TI  - Target platelet antigens of autoantibodies in patients with primary biliary
      cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, frequently
      associated with thrombocytopenia. As various immune abnormalities have been
      described in PBC, we hypothesized that thrombocytopenia is also an autoimmune
      phenomenon in these patients. We therefore assessed the frequency of platelet
      antibodies and their target platelet glycoprotein (GP) specificities. We
      investigated 66 PBC patients with a median disease duration of 25 months. Twenty
      two patients with alcoholic liver disease and thrombocytopenia served as
      controls. Specificities of platelet antibodies were determined by the monoclonal
      antibody-specific immobilization of platelet antigens (MAIPA) assay using
      monoclonal antibodies directed against GPIIb/IIIa and GPIb/IX. The notion that
      immunoglobulins are nonspecifically bound to platelets was further evaluated by
      the production of eluates from antibody-coated platelets. The specificities of
      antibodies in these eluates were again determined by the MAIPA assay. Twenty-six
      PBC patients had platelet antibodies, whereas antibodies were not detectable in
      control alcoholic patients. Seven of 13 thrombocytopenic PBC patients had
      detectable antibodies. Overall, GP Ib/IX and GP IIb/IIIa served in a similar
      frequency as target antigens. Antibody specificities were confirmed by the
      production of eluates from platelets. These studies provide evidence that
      antibodies are specifically bound to platelets in patients with PBC and that the
      development of immune phenomena in PBC may also involve immuno-mediated platelet
      destruction.

PMID- 9185751
TI  - Endoscopic variceal ligation in prophylaxis of first variceal bleeding in
      cirrhotic patients with high-risk esophageal varices.
AB  - To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on
      the rate of first esophageal variceal bleeding, we conducted a prospective,
      randomized trial in 126 cirrhotic patients with no history of previous upper
      gastrointestinal bleeding and with esophageal varices endoscopically judged to be
      at high risk of hemorrhage. The end-points of the study were bleeding and death.
      Life-table curves showed that prophylactic EVL significantly diminished the rate
      of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall
      mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative
      bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control
      group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and
      58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the
      time to death of both groups showed significantly lower mortality in the ligation
      group (P = .001). Patients undergoing EVL had few treatment failures and died
      mainly of hepatic failure. The lower risk in the EVL group was attributed to a
      rapid reduction of variceal size. Prophylactic EVL was more efficient in
      preventing first bleeding in patients with good condition (Child A) than in those
      with decompensated disease (Child B and C). We conclude that prophylactic EVL can
      decrease the incidence of first variceal bleeding and death over a period of 2
      years in cirrhotic patients with high-risk esophageal varices.

PMID- 9185752
TI  - Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with
      cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double
      blind study.
AB  - One hundred twenty-six patients with cirrhosis, hyperammonemia (>50 micromol/L),
      and chronic (persistent) hepatic encephalopathy (HE), which developed
      spontaneously without the existence of known precipitating factors, were enrolled
      in a randomized, double-blind, placebo-controlled clinical trial of intravenously
      administered L-ornithine-L-aspartate (OA). Patients with subclinical (grade 0,
      West-Haven criteria) hepatic encephalopathy (SHE), characterized by a prolonged
      number connection test A (NCT-A) time, and manifest HE (grades I and II, West
      Haven criteria) were included in the investigation. The trial was planned as a
      confirmatory clinical trial OA administered in a dose of 20 g/d, as well as
      placebo, were dissolved in 250 mL of 5% fructose and infused intravenously for a
      period of 4 hours during 7 consecutive days with a superimposed protein load at
      the end of the daily treatment period. Primary variables were postprandial venous
      ammonia and NCT-A performance time measured following OA or placebo infusions to
      evaluate the net effect of the treatment on the prevention of the protein-induced
      hyperammonemia, and on parameters such as NCT-A influenced by hyperammonemia.
      Mental state gradation, portal systemic encephalopathy index (PSEI), and fasting
      ammonia levels were estimated as additional efficacy parameters. The data
      presented are based on the total study sample (intent-to-treat analysis), which
      included 63 patients in the placebo group and 63 patients in the OA group. Of the
      126 patients, 114 met all the criteria for inclusion and completed the trial and
      treatment as outlined in the protocol (treated-per-protocol analysis). During
      baseline, the placebo and treatment groups were homogeneous with regard to mental
      states, NCT-A performance time, fasting venous blood ammonia levels, and Child
      Pugh criteria. Although a slight improvement occurred in the placebo group, NCT-A
      performance times (P < .001) and postprandial venous ammonia concentrations in
      the OA-treated group showed improvements in comparison with placebo. In addition,
      venous fasting blood ammonia concentration (P < .01), mental state gradation (P <
      .001), and PSEI (P < .01), which includes the mental state gradation, NCT-A time,
      and postprandial venous ammonia in this trial, improved to a much higher degree
      in the OA group than in the placebo group. In subgroups retrospectively
      classified according to their initial mental state gradation, OA showed
      differential but uniformly significant efficacies in patients with manifest HE
      with respect to ammonia-lowering, improvement in NCT times, and mental state
      gradation. In patients with initial SHE, OA revealed differences between the
      medications in the psychometric test used. Adverse events consisting of mild
      gastrointestinal disturbances were observed in 3 of the OA-treated patients (5%).
      OA infusion appears to be a safe, effective treatment of chronic (persistent)
      manifest HE in cirrhotic patients. Additional investigations are required to
      assess the efficacy of OA in patients with SHE, as well as in patients with more
      severe grades of HE.

PMID- 9185753
TI  - Cardiac muscarinic receptor function in rats with cirrhotic cardiomyopathy.
AB  - The pathogenesis of cirrhotic cardiomyopathy remains unclear. Because ventricular
      contractility is dependent on the interplay of stimulatory beta-adrenergic and
      inhibitory muscarinic receptors, we aimed to examine a possible role of
      muscarinic M2 receptor overactivity in a rat model of cirrhotic cardiomyopathy.
      Cirrhosis was induced by bile duct ligation (BDL), while controls underwent sham
      operations. Contractile responses to the muscarinic agonist carbachol were
      measured in situ in the autonomic-denervated pithed rat and in vitro in isolated
      ventricular papillary muscles. Ventricular sarcolemmal plasma membranes were
      isolated by sucrose density gradients, and muscarinic receptor characteristics
      were studied using 1-[N-methyl-3H]scopolamine (NMS). Membrane adenylyl cyclase
      activity was tested by a protein binding assay. Maximum first time derivative of
      peak ventricular systolic pressure (+dP/dt) for sham-operated and cirrhotic rats
      at baseline was 3,599 +/- 296 versus 1,226 +/- 63 mm Hg/sec (P < .01). Maximum
      first time derivative of ventricular diastolic relaxation (-dP/dt) for sham and
      cirrhotic rats at basal levels was -3,040 +/- 235 versus -864 +/- 59 (P < .01).
      The +dP/dt(max), and -dP/dt(max) responses to carbachol were blunted in the
      cirrhotic rats. The cirrhotic papillary muscles showed significantly less
      inhibition to incremental doses of carbachol than control rat muscles. Likewise,
      isoproterenol-stimulated membrane adenylyl cyclase activity was significantly
      less inhibited by carbachol doses in the cirrhotic rats. Membrane M2 receptor
      density and binding affinity in cirrhotic rat hearts were similar to controls. We
      conclude that muscarinic responsiveness was blunted in cirrhotic hearts, but this
      was not caused by receptor down-regulation, suggesting changes in postreceptor
      factors. These changes in muscarinic function are likely compensatory, and M2
      receptor overactivity is not involved in the genesis of cirrhotic cardiomyopathy.

PMID- 9185754
TI  - The successful treatment of symptomatic, refractory hepatic hydrothorax with
      transjugular intrahepatic portosystemic shunt.
AB  - Hepatic hydrothorax is a rare complication of portal hypertension. Conservative
      therapy may be successful but refractory hepatic hydrothorax is not uncommon.
      Management of refractory hydrothorax is usually ineffective and can result in a
      worsened clinical status. Transjugular intrahepatic portosystemic shunts (TIPS)
      lower portal pressure and have been used in the treatment of refractory ascites.
      The aim of this study was to determine the efficacy of TIPS in the treatment of
      symptomatic refractory hepatic hydrothorax. A TIPS was placed in 24 consecutive
      cirrhotic patients with symptomatic refractory hepatic hydrothorax. Five patients
      (20.8%) were Child's/Pugh class B and 19 (79.2%) were class C. All had undergone
      multiple thoracenteses and were hypoalbuminemic. Mean follow-up was 7.2 months
      (range, 0.25-49 months). Fourteen (58.3%) of 24 patients had complete relief of
      symptoms after shunt placement and did not require further thoracentesis. Five
      (20.8%) additional patients required fewer thoracenteses. Five (20.8%) patients
      developed worsening liver function and died within 45 days. In eight (66.7%) of
      12 patients with > or = 60 days of follow-up, the serum albumin increased by a
      mean of 1.2 g/dL (range, 0.1-2.2 g/dL). The Child's-Pugh score improved in 7
      (58.3%) of these 12 patients and two patients improved from class C to class A.
      These two patients no longer require liver transplantation. This study shows that
      TIPS can be effective in the management of symptomatic, refractory hepatic
      hydrothorax. Clinical and laboratory improvement may be seen and liver
      transplantation may become unnecessary.

PMID- 9185755
TI  - Assessment of the role of activin A and transforming growth factor beta in the
      regulation of AML12 cell growth.
AB  - The present study was conducted to determine the role of two autocrine factors,
      activin A and transforming growth factor beta (TGF-beta), in the growth
      regulation of AML12 hepatocytes. We overexpressed truncated type II activin
      and/or TGF-beta receptors in AML12 cells. In AML12 cells overexpressing truncated
      type II activin receptors (AML-tAR cells), the inhibitory effect of activin A on
      DNA synthesis was completely blocked. AML-tAR cells proliferated faster than
      parental cells, both in the presence and absence of epidermal growth factor
      (EGF). However, AML-tAR cells could not grow in soft agar. Follistatin augmented
      EGF-induced DNA synthesis in AML12 cells, whereas it was ineffective in AML-tAR
      cells. In AML12 cells overexpressing truncated type II TGF-beta receptor (AML-tTR
      cells), the inhibitory effect of TGF-beta on DNA synthesis was blocked. AML-tTR
      cells proliferated faster than parental cells, both in the presence and absence
      of EGF, but at a slower rate than that of AML-tAR cells. AML-tTR cells did not
      grow in soft agar. The growth rate of cells overexpressing both types of
      truncated receptors was identical to that of AML-tAR cells, and these cells did
      not grow in soft agar. These results indicate that both activin A and TGF-beta
      act as autocrine inhibitors of DNA synthesis in AML12 cells, and that the
      blocking of the actions of two factors does not lead to transformation. Activin A
      is a predominant autocrine factor in these cells.

PMID- 9185756
TI  - Germ-line mutations of the p16INK4(MTS1) gene occur in a subset of patients with
      hepatocellular carcinoma.
AB  - The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very
      recently has there been a suggestion of familial hepatocellular carcinoma (HCC).
      We have analyzed the status of the p16INK4(MTS1) gene, a cyclin-dependent kinase
      inhibitor, in 26 patients with HCC of different etiologies. Four patients carried
      hemizygous germ-line point mutations of the p16INK4(MTS1) gene, suggesting the
      existence of familial HCC involving this gene. The wild-type allele was lost in
      the tumor in 2 of these 4 patients. Three of the patients carrying a germ-line
      mutation had non-cirrhosis-associated HCC. No somatic mutations of p16INK4(MTS1)
      were observed in the 26 cases of HCC. The most common somatic alteration of the
      p16INK4(MTS1) gene in HCC was de novo methylation, which was detected in 48% of
      the cases. Low levels (21%) of p16INK4(MTS1) gene allele loss were observed.
      Altogether, these results indicate that alteration of the p16INK4(MTS1) gene
      plays an important role in the genesis of HCC.

PMID- 9185757
TI  - Production and role of interleukin-10 in concanavalin A-induced hepatitis in
      mice.
AB  - Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves
      the production of proinflammatory cytokines. Because interleukin (IL)-10 is a
      potent anti-inflammatory cytokine derived from macrophages and T cells and is
      produced within the liver, we investigated the role of IL-10 in modulating the
      hepatotoxicity and the secretion of cytokines following in vivo injection of Con
      A. IL-10 is produced early in the serum after Con A challenge. Neutralization of
      endogenous IL-10 by monoclonal antibodies (mAbs) increases the secretion of tumor
      necrosis factor alpha (TNF-alpha) (+111%), interferon gamma (IFN-gamma) (+92%),
      and IL-12 (+730%) 8 hours after Con A injection, and increases the
      hepatotoxicity, assessed by serum alanine transaminase (ALT) (+174%) measurement
      and by histology, 24 hours after induction of hepatitis. Conversely,
      preadministration of recombinant IL-10 reduces the production of these
      proinflammatory cytokines (-47%, -80%, and -47% for TNF-alpha, IL-12, and IFN
      gamma, respectively), and decreases neutrophil infiltration and ALT serum
      concentration (-74%) 8 hours after Con A challenge. We conclude that IL-10,
      either endogenously produced or exogenously added, has a hepatoprotective role in
      Con A-induced hepatitis, through its suppressive property on proinflammatory
      cytokine production, and that it might be of therapeutic relevance in human liver
      diseases involving activated T cells.

PMID- 9185758
TI  - Effects of the Japanese herbal medicine "Sho-saiko-to" (TJ-9) on in vitro
      interleukin-10 production by peripheral blood mononuclear cells of patients with
      chronic hepatitis C.
AB  - "Sho-saiko-to" (TJ-9) consists of 7 herbal components. In Japan, it is widely
      prescribed to patients with chronic viral liver disease. TJ-9 is known to
      suppress liver cancer development and possess macrobiotic effects, but its mode
      of action is not fully understood. This study investigated the following: 1)
      cytokine production levels, mainly interleukin (IL)-10, in peripheral blood
      mononuclear cells of chronic active hepatitis B and C patients, and healthy
      volunteers; 2) effects of TJ-9 on these productions; and 3) effects of each of
      its herb components on cytokine production in cell fractions. Results showed that
      without stimulants, IL-10 production in mononuclear cells of hepatitis B and C
      patients was significantly lower than that of healthy subjects (P < .01). IL-10
      production induced by either phytohemagglutinin (PHA) or pokeweed mitogen (PWM)
      in mononuclear cells of hepatitis C patients were significantly lower than in
      patients with hepatitis B (P < .01) and healthy subjects (P < .05). IL-10
      production induced by anti-CD3 or lipopolysaccharide (LPS) was significantly
      lower than in healthy subjects (P < .05). The addition of TJ-9 to the cultures
      strongly induced IL-10, and this induction was mainly attributable to the effects
      of 2 components (scutellaria root and glycyrrhiza root) on the
      monocyte/macrophage fraction. The production of IL-4 and IL-5 in cultures with
      concanavalin A (conA) was significantly higher in patients with hepatitis C than
      in the healthy subjects (P < .01; P < .05), but the addition of TJ-9 suppressed
      these increases by 25% to 33% (P < .01). Therefore, TJ-9 could adjust the
      decreased IL-10 production and the increased IL-4 and IL-5 production of
      mononuclear cells from patients with hepatitis C. Moderate regulation of the
      cytokine production system in patients with hepatitis C by using TJ-9 may be
      useful in the prevention of disease progression.

PMID- 9185759
TI  - Expression and release of the latent transforming growth factor beta binding
      protein by hepatocytes from rat liver.
AB  - In very recent studies it was established that transforming growth factor beta
      (TGF-beta), likely to be the most relevant fibrogenic cytokine and regulator of
      cell proliferation, differentiation, and matrix metabolism, is expressed by
      hepatocytes (parenchymal cell [PC]) and secreted from cultured PC in a latent
      form incapable of receptor binding. The structural composition of the latent TGF
      beta complex secreted by cultured PC is unknown. In some TGF-beta expressing cell
      types this cytokine is released as a large molecular weight complex containing in
      addition to the TGF-beta latency associated peptide (LAP) a disulfide bonded
      latent TGF-beta binding protein (LTBP), of which the existence and function in
      liver is hitherto unknown. This study is directed to the identification of LTBP
      expression in rat PC. Cells were isolated from rat liver with the collagenase
      method and analyzed for LTBP before and during culture under standard conditions
      using alkaline phosphatase anti-alkaline phosphatase (APAAP) immunostainings,
      metabolic labeling, messenger RNA (mRNA) detection (reverse-transcription
      polymerase chain reaction [RT-PCR]) and sequencing, and immunoblotting of gel
      chromatographically separated cell extracts and conditioned media, respectively.
      APAAP immunostainings applying a specific polyclonal LTBP-antiserum (ab 39)
      indicated expression of LTBP in PC of liver in situ and freshly isolated PC but a
      strong expression in cultured PC. Transcripts of LTBP-1 were detected by RT-PCR
      and confirmed by sequence analyses. Metabolic labeling of PC with [35S]-Met/Cys
      followed by immunoprecipitation of cell lysates with LTBP antiserum confirmed the
      synthesis of the high molecular mass complex of 250 kd containing LTBP with a
      molecular mass of 160 kd. Latent TGF-beta complexes, associated with LTBP related
      proteins, could be separated from both extracts and conditioned media of PC by
      gel filtration chromatography. They confirmed the release of the large latent TGF
      beta complex from PC. Investigations of immunocytochemical LTBP staining under
      different culture conditions (TGF-beta supplementation, extracellular matrices)
      point to concordant variations of LTBP and TGF-beta expression. The results
      suggest a role for PC in paracrine- and autocrine-mediated effects of TGF-beta,
      which might be important for various cell activities in healthy and diseased
      liver.

PMID- 9185760
TI  - Absence of NO synthase type II expression in fetal liver from pregnant rats under
      septic shock conditions.
AB  - Treatment of rats at 21 days' gestation with lipopolysaccharide (LPS) induced
      type II NO synthase (iNOS) expression in maternal liver but completely failed to
      elicit this response in the corresponding fetal tissue. The impaired response of
      fetal liver cannot be attributed to alterations in the sensitivity of this organ
      to LPS or to proinflammatory cytokines involved in iNOS expression (tumor
      necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma]), because
      cultured fetal and adult hepatocytes similarly responded to these factors.
      Measurement of TNF-alpha and IFN-gamma levels in maternal and fetal serum showed
      a restricted permeability of placenta to these cytokines, results that were in
      agreement with the absence of iNOS expression in fetal liver. Moreover, analysis
      of nuclear factor kappaB, which is required for iNOS expression, showed an
      activation in nuclear extracts from livers of mothers under septic shock
      conditions but not in the corresponding fetal livers. However, cultured fetal
      hepatocytes prepared from mothers in septic shock displayed an anomalous pattern
      of iNOS expression, including a decreased response to LPS as well as a shift in
      sensitivity to TNF-alpha. These hepatocytes from LPS-treated mothers showed
      significant expression of iNOS in the absence of added stimuli. These results
      suggest that there is a priming of the fetal hepatocytes from mothers with septic
      shock. The characterization of the factors causing this priming process might
      provide additional clues understanding the control of iNOS expression in liver.

PMID- 9185761
TI  - Relaxing effect of interleukin-1 on rat cultured Ito cells.
AB  - Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta
      produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular
      smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we
      evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were
      isolated from the livers of male Wistar rats and cultured for 24 hours.
      Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and
      intensity of fluorescence of cGMP were examined using a confocal laser
      microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and
      the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito
      cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta
      were observed over 12 hours, and the area of the same Ito cell was compared
      before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L
      arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell
      relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence
      of iNOS was observed, and fluorescent intensity of cGMP increased after addition
      of IL-1beta. Intracellular cGMP concentration increased dose-dependently after
      addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated
      group compared with the untreated group. Relaxation of Ito cells by IL-1beta
      treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by
      SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and
      relaxes the cells via cGMP.

PMID- 9185762
TI  - Serum IgA, IgG, and IgM antibodies directed against acetaldehyde-derived
      epitopes: relationship to liver disease severity and alcohol consumption.
AB  - Chronic ethanol ingestion has been suggested to trigger the formation of
      antibodies that recognize acetaldehyde-protein condensates. In this study, assays
      for immunoglobulin (Ig) A, IgG, and IgM antibodies to acetaldehyde-derived
      adducts were performed on sera of 140 alcohol consumers, 19 patients with
      nonalcoholic liver disease (NALD), 35 healthy nondrinking controls, and 10
      nondrinking patients with IgA or IgG myeloma. Anti-acetaldehyde (Ach)-adduct
      antibodies of each Ig isotype were found from the alcohol abusers. In alcoholic
      liver disease (ALD, n = 86) IgA titers were elevated in 69% of the patients.
      These titers were significantly higher than those from patients with NALD (P <
      .001), nondrinking controls (P < .001), or heavy drinkers (n = 54) without any
      clinical and biochemical signs of liver disease (P < .001). In contrast, anti
      adduct IgG titers were significantly elevated both in ALD and in heavy drinkers
      as compared with patients with NALD (P < .001) or nondrinking controls (P < .01
      and P < .05, respectively). The anti-adduct immunoglobulin (Ig)A, IgG, and IgM
      titers in patients with alcoholic liver disease (ALD) correlated with the
      combined clinical and laboratory index of liver disease severity (r(s) = .497, P
      < .001; r(s) = .361, P < .01; and r(s) = .322, P < .01). Anti-adduct IgA titers
      also correlated with serum bilirubin (r = .768, P < .001) and interleukin 6 (r =
      .504, P < .001). Anti-adduct IgG titers were, in turn, found to correlate with
      the presence of inflammation (P < .01) and necrosis (P < .01). During follow-up
      studies of individual patients, parallel changes were observed in the anti-adduct
      IgG titers, disease severity, and serum markers of fibrogenesis. The present
      results provide evidence that antibodies representing distinct Ig classes
      directed against acetaldehyde (Ach)-derived adducts of proteins are formed in
      alcoholic patients showing an association with the severity of liver disease. The
      follow-up data also support an association between such immune responses and the
      aggravation of liver disease.

PMID- 9185763
TI  - Decrease of ischemic injury to the isolated perfused rat liver by loop diuretics.
AB  - Recent studies suggest a major role played by sodium in the pathogenesis of
      ischemic liver injury: in these studies, sodium-free media have been shown to
      offer protection against hypoxic injury to isolated hepatocytes. As sodium-free
      perfusions of the isolated rat liver proved impossible because of extensive
      vasoconstriction, we assessed the effects of two inhibitors of the Na+-K+-2Cl-
      cotransporter, the loop diuretics furosemide and bumetanide, on ischemic liver
      injury. In untreated control livers lactate dehydrogenase (LDH) efflux
      immediately after reperfusion after 60 minutes of ischemia at 37 degrees C was
      1666 +/- 473 U/L. When livers were pretreated with furosemide or bumetanide
      before the ischemic period, LDH efflux was only 773 +/- 292 U/L and 702 +/- 183
      U/L respectively (P < .01). LDH activity in the effluent of the pretreated livers
      remained significantly below the values of ischemic control livers for the whole
      reperfusion period of 90 minutes. Bile flow in the postischemic phase was
      improved by pretreatment with furosemide or bumetanide. The increase in
      intracellular sodium, as measured by 23Na-NMR, was attenuated from 193% +/- 71%
      during 60 minutes of ischemia in controls to 148% +/- 80% after bumetanide
      application (P < .05). Also, after 120 minutes of warm ischemia, LDH and
      aspartate aminotransferase release were significantly decreased and bile flow
      increased by pretreatment with bumetanide. Thus, both furosemide and bumetanide
      showed a clear benificial effect on rat livers subjected to warm ischemia. These
      data suggest that one means by which sodium ions are accumulated during liver
      ischemia might be the Na+-K+-2Cl- cotransporter, which is blocked by furosemide
      and bumetanide.

PMID- 9185764
TI  - Calcium-dependent DNA damage and adenosine 3',5'-cyclic monophosphate-independent
      glycogen phosphorylase activation in an in vitro model of acetaminophen-induced
      liver injury.
AB  - Acetaminophen (N-acetyl-p-aminophenol [APAP]) hepatotoxicity is a process
      characterized by Ca2+ deregulation. Cellular functions utilizing Ca2+ as a second
      messenger molecule affect both cytosolic and nuclear signal transduction. Many
      studies have independently shown Ca2+-related effects on target molecules in
      response to toxic doses of APAP; however, the primary Ca2+ target resulting in
      liver necrosis has not been determined. We hypothesize that Ca2+-dependent DNA
      damage is a critical event in liver necrosis caused by alkylating hepatotoxins.
      In this study, Ca2+-dependent endonuclease activity was determined from DNA
      single-strand lesions measured by fluorometric analysis of DNA unwinding. The
      status of cytosolic Ca2+ was determined by measuring Ca2+-dependent activation of
      glycogen phosphorylase a. Primary cultures of mouse hepatocytes exposed to a
      toxic concentration of APAP showed twofold and greater increases in glycogen
      phosphorylase a stimulation at 6 hours, which was reversible with Ca2+-chelating
      agents. Cell death was preceded by a large decline in intact, double-stranded
      DNA. Following toxic administration of APAP, the percentage of total double
      stranded DNA was significantly reduced by 2 hours. At 6 and 24 hours, genomic
      integrity was compromised by 26% and 37%, respectively, compared with untreated
      controls. Hepatotoxic effects of APAP-mediated Ca2+ deregulation were confirmed
      in both primary mouse hepatocytes and the human hepatoblastoma HepG2 cell line by
      lactate dehydrogenase (LDH) release and tetrazolium reduction using the 3-4,5
      dimethylthiazole-2-yl-2,5-diphenyltetrazolium bromide thiazol blue(MTT) assay.
      The Ca2+ chelator, ethylene glycol-bis (beta-aminoethyl ether) N',N',N', N'
      tetraacetic acid (EGTA), blocked APAP-induced phosphorylase a activation and
      necrotic cell death, but failed to inhibit phosphorylase a activation by the
      adenosine 3',5'-cyclic monophosphate (cAMP) analogue, dibutyryl cAMP, indicating
      little or no contribution of the cAMP pathway to phosphorylase a stimulation
      during APAP-induced necrotic death. Results with these in vitro models of liver
      injury are interpreted as supporting the hypothesis that increased Ca2+
      availability plays a major role in the progression of APAP-dependent cellular
      necrosis, and that the nucleus is a critical target for APAP hepatotoxicity.

PMID- 9185765
TI  - Prevalence of hereditary hemochromatosis in a Massachusetts corporation: is
      Celtic origin a risk factor?
AB  - The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at
      1:250 in Caucasian adults. Little is known about ethnic subpopulations that might
      be at increased risk for this disease. HLA data have suggested a Celtic origin
      for HHC. Screening for HHC was offered to all employees of the Massachusetts
      Polaroid Corporation. Participants with a transferrin saturation of >55% or >45%
      and an elevated serum ferritin concentration on two screenings were referred for
      liver biopsy. The diagnosis of HHC was based on histological criteria,
      quantitative hepatic iron determination, hepatic iron index, and the phlebotomy
      requirement for iron depletion. Participants completed a questionnaire regarding
      their ethnic background. Two thousand two hundred ninety-four employees were
      screened, and 5 cases of HHC were detected. All 5 cases involved Caucasian men,
      yielding a prevalence of 1:395 for the Caucasian population. Four of the 5 cases
      were of 100% British-Irish ancestry based on the country of origin of their
      grandparents. Additional analysis revealed that the majority of grandparents of
      all 4 individuals came from Ireland or Wales. The exact two-tailed trend test
      showed a significant association of HHC with Celtic background (P = .012). The
      estimated cost of screening per patient identified was $18,041. Polaroid
      Corporation has a high representation of employees of British-Irish ancestry. Our
      data suggest that they are at high risk for developing HHC. A significant
      association of HHC with Celtic ancestry was found in this subpopulation,
      supporting the concept of a Celtic origin for this disease.

PMID- 9185766
TI  - Hepatic cholesterol metabolism in human obesity.
AB  - Hepatic cholesterol metabolism was studied in operative liver biopsies from 17
      morbidly obese subjects and compared with that in samples from 15 nonobese
      controls. The aim was to understand the mechanisms causing the hypersecretion of
      cholesterol into bile. The content of cholesteryl esters was increased threefold
      in the liver of obese subjects compared with that of the controls (P < .0001).
      The activity and the messenger RNA (mRNA) level of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG CoA) reductase, the rate limiting enzyme for cholesterol
      synthesis, were higher in the obese subjects compared with the nonobese subjects
      (75% and 140%, respectively; P < .01). In the obese subjects, the activity and
      mRNA level of cholesterol 7alpha-hydroxylase, which regulates the catabolism of
      cholesterol to bile acids, were also increased by 140% (P < .05) and 180% (P =
      .06), respectively, as compared with the controls. There was a significant
      correlation between the activities and the mRNA levels of cholesterol 7alpha
      hydroxylase among the obese subjects (r = +0.65, P < .01). The activities of acyl
      coenzyme A:cholesterol acyltransferase (ACAT), which governs cholesteryl ester
      formation, in obese and nonobese patients were 12.5 +/- 1.7 and 8.1 +/- 1.2
      pmol/min/mg protein, respectively (P < .05), and the low-density lipoprotein
      (LDL) receptor mRNA levels were 5.3 +/- 0.7 and 4.5 +/- 0.9 molecules of
      mRNA/microg of RNA, respectively. We conclude that the activities of three key
      enzymes in hepatic cholesterol metabolism were increased in morbidly obese
      subjects compared with nonobese controls, as were mRNA levels of HMG CoA
      reductase and cholesterol 7alpha-hydroxylase. The mRNA level of the LDL receptor
      in the obese subjects was not significantly changed. The hypersecretion of
      cholesterol occurring in obesity is neither due to a reduced conversion of
      cholesterol to bile acids nor to a decreased esterification of hepatic
      cholesterol but may be due to an increased synthesis of cholesterol.

PMID- 9185767
TI  - Cholesterogenesis, lipogenesis, cholesterol degradation to bile acids, and
      histopathology of the liver in LA/N-cp obese rats.
AB  - Various lipid parameters were determined in lean control and LA/NIH-corpulent
      (LA/N-cp) rats, a normotensive strain showing metabolic characteristics
      associated with human Type IV hyperlipidemia. Hepatic and plasma total
      cholesterol, high density lipoproteins (HDL) cholesterol and triglycerides were
      significantly higher in the obese group than in the control group. Depending upon
      whether the data were expressed as per gram tissue or per organ, the rates of de
      novo fatty acid synthesis in the liver and adipose tissue were higher by 61% to
      127% (P < .05) and 79% to 355% (P < .05), respectively, in the obese group
      compared with the lean control group. Similarly, hepatic rate of cholesterol
      synthesis was higher by 46% to 107% (P < .05) in the obese animals compared with
      the lean ones. In vivo hepatic rate of HDL2 cholesterol degradation to bile acids
      was lower in the obese group by 48% to 63% (P < .05). This was confirmed in the
      perfused liver in spite of the fact that cholesterol uptake from HDL2 was 3- to 4
      fold higher in the obese group. These changes in lipid parameters of the obese
      animals were neither caused by hyperphagia because they were pair-fed with the
      control group nor caused by increased rate of food consumption because they were
      meal-fed. At the same time, all these lipid parameters were 17% to 20% higher in
      ad libitum-fed obese than in pair-fed obese group. Histopathological evaluation
      of the livers in the obese and control groups also showed prominent lipid
      droplets in the cytoplasm of the obese liver but not in the lean control liver.
      Thus, the possible causes of obesity in the LA/N-cp obese rats are higher
      synthetic rates of lipids coupled with lower rate of degradation of cholesterol
      to bile acids.

PMID- 9185768
TI  - Intestinal absorption and enterohepatic cycling of biliary iron originating from
      plasma non-transferrin-bound iron in rats.
AB  - In iron overload, non-transferrin-bound iron (NTBI) is found in plasma and is
      rapidly removed by hepatocytes. Some of this NTBI is excreted into bile. Biliary
      excretion of NTBI, in the form of an iron-deferiprone chelate, is greatly
      increased by deferiprone, an iron chelator. The aim of this study was to test
      whether biliary iron as such or as an iron-deferiprone chelate (both originating
      from plasma NTBI) is absorbed from the intestine and re-secreted into bile. In
      healthy biliary fistula (donor) rats, biliary 55Fe originating from plasma NTBI
      was obtained by injecting Fe citrate (to saturate transferrin) followed by 55Fe.
      This biliary 55Fe was infused into the duodenum of (recipient) rats whose
      transferrin was saturated or unsaturated. Similar experiments were performed
      using iron-overloaded (donor) rats given deferiprone, followed by infusion of the
      biliary 55Fe-deferiprone chelate into iron-overloaded (recipient) rats. The
      results show that in healthy (recipient) rats, duodenal infusion of 55Fe from
      NTBI was followed by increased plasma 55Fe when transferrin was unsaturated, or
      by biliary excretion of 55Fe when transferrin was saturated, indicating
      intestinal absorption of 55Fe. In iron-overloaded rats, neither plasma nor bile
      became radioactive, indicating no intestinal absorption of iron from the
      deferiprone chelate. We conclude that biliary iron, originating from NTBI, is
      absorbed from the intestine, and undergoes enterohepatic circulation if
      transferrin is saturated. In iron-overloaded rats, biliary iron originating from
      plasma NTBI and present as an iron-deferiprone chelate in bile is not absorbed.

PMID- 9185769
TI  - Targeted nucleotide exchange in the alkaline phosphatase gene of HuH-7 cells
      mediated by a chimeric RNA/DNA oligonucleotide.
AB  - Although a variety of methods has been devised for modification of hepatic genes,
      none has been effective for long-term correction of genetic disorders. In this
      study, we employed a recently described novel experimental strategy for site
      directed nucleotide exchange in genomic DNA of HuH-7 human hepatoma cells. A
      chimeric 2'-O-methylated-RNA/DNA oligonucleotide containing sequences
      complementary to 25 bases of the alkaline phosphatase gene was constructed as a
      duplex containing a G to A substitution at nucleotide 935. Cells were transfected
      with oligonucleotides for 48 hours, then harvested for DNA isolation and
      polymerase chain reaction (PCR) amplification of exon 6 of the alkaline
      phosphatase gene. Colony lifts were hybridized to 17 mer 32P-labeled
      oligonucleotide probes specific to the 935-G and 935-A sequences. Hybridizing
      colonies were grown, plasmid DNA isolated, and sequenced. Transfection efficiency
      was determined at 24 hours by nuclear uptake of fluorescein-12-dUTP-labeled
      chimeric oligonucleotides. Colonies hybridizing with the 935-A probe were
      identified only from cells transfected with the specific chimeric
      oligonucleotide; and there was no evidence of cross-hybridization. Conversion of
      G to A at nucleotide 935 occurred at an overall frequency of up to 11.9% and when
      corrected for transfection efficiency approached 43%. No other alterations were
      detected in the sequence of exon 6 with the targeted nucleotide exchange. These
      results show that a single base pair alteration in the alkaline phosphatase gene
      of HuH-7 cells can be introduced at a relatively high frequency following
      transfection with chimeric RNA/DNA oligonucleotides. This technique offers a
      novel and potentially powerful strategy for site-directed hepatic gene alteration
      without the use of viral-based vectors.

PMID- 9185770
TI  - Prediction of abstinence from ethanol in alcoholic recipients following liver
      transplantation.
AB  - The prediction of abstinence from ethanol may be crucial to the optimal selection
      of liver transplantation candidates with alcoholism. Of 84 consecutive end-stage
      alcoholic patients who underwent transplantation (1986-1994) at our institution,
      we analyzed 63 long-surviving recipients for pretransplantation variables to
      predict posttransplantation abstinence (follow-up: 49.3 +/- 21 mo). Thirty-three
      pretransplantation variables were reviewed from our transplantation data base and
      supplemented and confirmed with interviews with recipients. The psycho-social
      inclusion criteria included the following: patient recognition of alcoholism, a
      domicile, an occupation, and at least one close personal relationship. The
      incidence of abstinence from ethanol was (50/63) 79%. A logistic regression of
      the 33 variables in conjunction with our above inclusion criteria accurately
      predicted abstinence (90% accuracy, chi2 model, P < .00001) based on the absence
      of previous history of any illicit drug use (Drug Use: yes = 1/no = 0), the
      presence of an active, personal life insurance policy (Life Ins: yes = 1/no = 0),
      number of alcoholic sisters (ETOH-SIS), and the length of pretransplantation
      abstinence (PRE-TRANS-ABS, mos): Prob. of abstinence = 1/1 + e(-F), F = -0.33 +/-
      0.89 (DRUG USE) -1.02 (LIFE INS) -1.68 (ETOH-SIS) +0.24 (PRE-TRANS-ABS). In
      contrast, receiver-operating characteristic curve analysis found that 7 and 9
      months of pretransplantation abstinence were the best cut-off points in
      predicting subsequent abstinence, but poor utility was noted at these points with
      this specific value alone (sensitivity 61-84%, specificity 64-68%). A separate
      analysis of high-risk patients with poly-drug use (n = 15, alcohol recidivism
      8/15, 53%) and the remaining low-risk group of purely alcohol dependent patients
      (n = 48, alcohol recidivism 5/48, 10%) found no combination of variables was
      predictive of abstinence in either group. The length of pretransplantation
      abstinence is a relatively poor predictor of posttransplantation abstinence.
      Variables of comorbid substance use, social function, and possibly family history
      are more predictive in conjunction with our standard criteria and might be useful
      as tools in evaluating liver transplantation candidates whose primary diagnosis
      is alcohol-induced cirrhosis.

PMID- 9185771
TI  - Liver transplantation for alcoholic liver disease: evaluation of a selection
      protocol.
AB  - We have used a formal transplant protocol to select patients with alcoholic liver
      disease (ALD) for transplantation. We retrospectively analyzed all the patients
      with ALD who were referred specifically for transplantation to our Liver Unit
      between 1987 and 1994. Patients were selected for liver transplantation if they
      had end-stage liver disease and had remained abstinent from the time they were
      medically advised to stop alcohol intake. Of the 180 patients referred for
      transplantation, 43 (none of whom were transplanted) had case records
      insufficiently complete for full analysis; this may bias the analysis. Of the
      remaining 137 patients, 39 were transplanted and 4 were awaiting transplantation
      at the time of analysis. Of the patients who were not accepted for
      transplantation, 13 died during the assessment, 7 were considered to be unlikely
      to survive the procedure, 29 were found to be medically unsuitable, 16
      psychologically unsuitable, 7 patients refused the offer of transplantation, and
      an additional 19 either showed clinical improvement or were considered too well
      for transplantation. Special investigations, such as brain computerized
      tomography (CT) scan and echocardiograph, changed the clinical decision to
      transplant in only a small number of cases (4% and 5%, respectively). Nine of the
      transplanted patients died and the remaining were followed up for a median of 25
      (range, 7-63) months. One year actuarial survival for the transplanted patients
      was 79%, for those considered too sick was 0%, for medically unsuitable patients
      was 44%, for psychologically unsuitable patients was 65% and for those considered
      too well was 94%. Only 5 of the transplanted patients (13%) reverted to drinking.
      The observed actuarial survival of nontransplanted patients was compared with the
      expected survival calculated by 'the Beclere model.' The observed actuarial
      survival in the nontransplanted groups was much better than anticipated from the
      Beclere model, which therefore, is not applicable to our patients. The
      proportional hazards regression analysis of our nontransplanted patients
      identified serum bilirubin, serum albumin, blood urea, ascites, and spontaneous
      bacterial peritonitis as factors significantly predictive of their probability of
      survival. Using a model based on these parameters, the expected survival of our
      transplanted patients was calculated. Although we applied the model to a
      different population, the observed actuarial survival in the transplanted
      patients was found to be better than their expected survival (P < or = .001). Our
      protocol was useful in selecting suitable patients with ALD for liver
      transplantation, which resulted in significant survival advantage with low
      recidivism rate.

PMID- 9185772
TI  - Survival after liver transplantation in cirrhotic patients with and without
      hepatocellular carcinoma: a comparative study.
AB  - Cumulative recurrence after surgical resection for hepatocellular carcinoma (HCC)
      is very high. Several retrospective analyses have shown that liver
      transplantation was more effective than resection for patients with HCC at early
      tumor stages. Consequently, in January 1990, we decided to prospectively indicate
      orthotopic liver transplantation (OLT) as the first surgical treatment for small,
      localized HCC in cirrhotic patients without nodal involvement independently of
      the degree of liver function. The aim of this prospective cohort study was to
      analyze prognosis, recurrence rate, and survival after liver transplantation in
      patients in whom the main indication was HCC with cirrhosis. Thirty-eight
      patients in whom the main indication for liver transplantation was HCC and
      hepatic cirrhosis were compared with 136 transplantations because of cirrhosis
      without tumor, performed in our unit from January 1990 to December 1995. HCC
      arising in noncirrhotic livers and those incidently discovered after OLT were
      excluded from the study. Chemoembolization using doxorubicin, lipiodol, and
      Gelfoam was performed before OLT in 31 patients with good liver function. There
      were no differences in gender, but HCC patients were older (57 +/- 7 vs. 50 +/-
      10 years [P < .001]). Liver function was better in HCC (Child-Pugh score: 6.9 +/-
      2 vs. 8.6 +/- 1.8; P < .001), and hepatitis C virus antibody was positive in 31
      (82%) vs. 51 (37%) (P < .007). Seven tumors had bilobar involvement (18%).
      Capsule was present in 22 (58%). The mean size of the tumor was 3.4 +/- 2 cm.
      Seventeen tumors (45%) were larger than 3 cm, and 4 (11%) were larger than 5 cm.
      The average number of nodules was 2 +/- 1. The tumor-node-metastasis stage of the
      tumors was pT1 in 6 patients (16%), 11 were pT2 (29%), 12 were pT3 (31%), and 9
      were pT4 (24%). Seven patients were retransplanted in the HCC group (18%) and 19
      (14%) in the nontumor group (not significant). Tumor recurrence was detected in
      three patients (8%). One, 3-, and 5-year survival rates were 82% vs. 79%, 75% vs.
      71%, and 63% vs. 68%, respectively, for patients with and without HCC, and no
      differences were found between the two groups (P = .84). Survival was
      significantly reduced in patients with a macroscopic vascular invasion and tumors
      greater than 5 cm in diameter. Recurrence and mortality after liver
      transplantation in cirrhotic patients with carefully selected HCC are similar to
      the results in cirrhotic patients without tumor.

PMID- 9185773
TI  - Hepatitis C in a French population-based survey, 1994: seroprevalence, frequency
      of viremia, genotype distribution, and risk factors. The Collaborative Study
      Group.
AB  - The aims of this study were the following: 1) to estimate the prevalence of
      hepatitis C virus (HCV) antibody (anti-HCV) in a population-based survey of
      French residents not selected for risk factors; 2) to investigate the association
      between anti-HCV seropositivity, viremia, the infecting HCV genotype, and the
      alanine transaminase (ALT) level; and 3) to identify risk factors for HCV
      infection by a nested case control study within this survey sample. The anti-HCV
      seroprevalence survey was performed in 6,283 volunteers (20- to 59-years-old)
      randomly selected from 45,377 consecutive individuals undergoing routine medical
      checkup in social security medical centers covering 4 of the 22 "regions" of
      France. Seventy-two volunteers were anti-HCV positive, a crude prevalence of
      1.15%. Fifty percent of these positive volunteers also had an abnormal ALT level
      and 81% were HCV-RNA positive by polymerase chain reaction (PCR). The prevalence
      weighted for age, sex, and place of residence was 1.05% (95% CI: 0.75-1.34). The
      weighted prevalence was lower among men > 40-years-old (0.5%; 95% CI: 0.1-1.0)
      and was close to 1% in all other age and sex groups. Prevalence was inversely
      correlated with socioprofessional status with the highest rate being found among
      those with no paid employment (2.2%; 95% CI: 1.3-3.0). The HCV prevalence (1.7%;
      95% CI: 1.0-2.3) was highest in southeastern France. Seventy-eight percent of
      positive intervenous (I.V.) drug abusers were infected with HCV genotypes 1a or
      3, whereas 80% of the transfusion-associated cases were infected by HCV genotypes
      1b or 2a. Only three variables were significantly associated with HCV
      seropositivity in multivariate analysis: I.V. drug abuse (21 cases, 14 men all <
      40-years-old), previous transfusion (22 cases, 18 women), and not having paid
      employment. Although routes of transmission other than I.V. drug abuse and
      transfusion may not be formally excluded they were not found to be statistically
      significant. Hepatitis C appears to be a major public health concern in France. A
      more active screening policy may be required because only 17 of 72 cases (24%)
      were aware of their HCV seropositivity before enrollment in the study.

PMID- 9185774
TI  - Clearance of hepatitis B surface antigen after bone marrow transplantation: role
      of adoptive immunity transfer.
AB  - Adoptive immunity transfer has been reported to be effective in clearing chronic
      hepatitis B virus (HBV) infection. Two hundred twenty-six patients who received
      allogeneic bone marrow transplantation (BMT) between May 1990 and September 1995
      were screened for hepatitis B markers. Twenty-one patients were hepatitis B
      surface antigen (HBsAg) positive before BMT. The median follow-up period was 20
      months (range, 2-59 months). Two of these patients had sustained clearance of HBV
      infection after transplantation. Both patients were hepatitis B e antigen (HBeAg)
      negative, hepatitis B e antibody (anti-HBe)-positive, and serum HBV DNA-negative
      (by dot-blot hybridization) before BMT. Both had a flare in the serum alanine
      transaminase (ALT) level around the time of HBsAg clearance. Sustained clearance
      of HBsAg was observed in 2 of the 5 patients who received hepatitis B surface
      antibody (anti-HBs)-positive marrow but in none of the 16 patients who received
      anti-HBs-negative marrow (P < .05). One additional patient who received anti-HBs
      positive marrow had transient HBsAg seroconversion. Among the 18 patients who
      remained persistently HBsAg-positive after BMT, 3 had HBeAg seroconversion and 3
      had reversion to HBeAg positivity. In this study, we found a significant
      association between clearance of HBV infection and anti-HBs-positive bone marrow
      donors. Adoptive immunity transfer is effective in clearing HBV from patients
      with chronic HBV infection.

PMID- 9185776
TI  - A hepatitis B virus mutant with a new hepatocyte nuclear factor 1 binding site
      emerging in transplant-transmitted fulminant hepatitis B.
AB  - Hepatitis B virus (HBV) DNA was cloned from serum of a heart transplant recipient
      who died from fulminant hepatitis B transmitted by the donor. Restriction enzyme
      analyses of the clones obtained by conventional cloning yielded six HBV variants:
      a major species (pF-1) representing 88% and five minor species (pF-2 to pF-6),
      each representing 2% to 4% of the clones. The complete nucleotide sequence of
      these six variants revealed that five of the six viral genomes, including pF-1,
      carried a novel 11 base pair (bp) insertion in the core promoter region as well
      as an 18 bp and an 108 bp in-frame deletion in the pre-S1 region not present in
      the donor. One genome was identical to the sequence of the donor. Functional
      analyses of HBV clones generated by in vitro mutagenesis and cassette exchange
      showed that the 11 bp insertion is a strong binding site for hepatocyte nuclear
      factor 1 (HNF-1). In transient transfection experiments, the novel HNF-1 sequence
      motif was shown to result in enhanced viral replication. Immunohistochemical
      analyses revealed high levels of cytoplasmic and nuclear hepatitis B core antigen
      (HBcAg) and only scattered hepatitis B surface antigen (HBsAg) expression in the
      liver. The data in our immunosuppressed patient showed that HBV variants can
      rapidly accumulate in severe hepatitis B and suggest that the novel HNF-1 binding
      site may have contributed to the fulminant clinical course, possibly via enhanced
      viral replication.

PMID- 9185775
TI  - Interferon alpha induces disorder of lipid metabolism by lowering postheparin
      lipases and cholesteryl ester transfer protein activities in patients with
      chronic hepatitis C.
AB  - The effect of recombinant interferon alpha 2a (rIFN-alpha2a) on serum lipoprotein
      metabolism was assessed in 39 patients with chronic viral hepatitis C. rIFN
      alpha2a was administered intramuscularly at a dose of 9 x 10(6) U/d for 2 weeks
      and then for 3 times a week over 6 months. The serum cholesterol concentration
      significantly decreased one week after rIFN-alpha2a administration. Approximately
      67% of this decrease was attributed to the reduction of high-density lipoprotein
      (HDL)-cholesterol; a decrease in HDL2-cholesterol was more evident. By contrast,
      serum triglyceride levels, largely derived from very-low density lipoprotein
      (VLDL), significantly increased following rIFN-alpha2a treatment. Lipoprotein
      lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin
      plasma were reduced by 75.7% and by 79.4%, respectively, and decreases in plasma
      cholesteryl ester transfer protein (CETP) activity and its protein mass were also
      observed. However, prothrombin time was ameliorated by rIFN-alpha2a, suggesting
      that the decrease in LPL, HTGL, and CETP activities may not be due to a reduction
      in protein synthesis by the liver. Simple correlation analysis demonstrated that
      the changes in LPL activity before and after 2 weeks of treatment with rIFN
      alpha2a showed a significant negative correlation with changes in serum
      triglyceride and VLDL-triglyceride and a positive correlation with changes in HDL
      cholesterol and HDL2-cholesterol. These results suggest a major contribution of
      reduced LPL activity with regard to the lipoprotein disorders. In conclusion,
      rIFN-alpha2a treatment on patients with chronic hepatitis C causes marked changes
      in serum lipoprotein metabolism associated with decreases in LPL, HTGL, and CETP
      activities.

PMID- 9185778
TI  - The molecular virology of hepatitis C.

PMID- 9185777
TI  - Processing/activation of CPP32-like proteases is involved in transforming growth
      factor beta1-induced apoptosis in rat hepatocytes.
AB  - Apoptosis induced in rat hepatocytes by transforming growth factor beta1 (TGF
      beta1) was accompanied by the activation of interleukin-1beta converting enzyme
      (ICE)-like proteases. Cell lysates were isolated at various times after TGF-beta1
      treatment and analyzed for ICE and CPP32-like activity, using N-acetyl-Tyr-Val
      Ala-Asp-7-amino-4-methylcoumarin (Ac-YVAD.AMC) and benzyloxycarbonyl-Asp-Glu-Val
      Asp-7-amino-4-trifluoromethylcoumarin (Z-DEVD.AFC), respectively. CPP32-like but
      not ICE protease activity increased in a time dependent manner and preceded the
      onset of apoptosis. Kinetic studies in cell lysates indicated that more than one
      CPP32-like protease was being activated. This was confirmed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/Western blotting of TGF
      beta1-treated cells, which showed limited processing of CPP32 as shown by the
      appearance of the catalytically active p17 subunit. Loss of pro-Mch3alpha was
      also observed but the catalytically active p19 subunit was not detected.
      Staurosporine, which induced a much greater level of hepatocyte apoptosis,
      produced a concomitant increase in CPP32/Mch3alpha processing as shown by the
      appearance of the p17/p19 subunits and the corresponding increase in CPP32-like
      protease activity. Apoptosis, CPP32/Mch3alpha processing and the increase in
      CPP32-like protease activity induced by TGF-beta1 and staurosporine were
      abolished in hepatocytes pretreated with Z-Asp-Glu-Val-Asp (OMe)
      fluoromethylketone (Z-DEVD.FMK) or Z-Val-Ala-Asp (OMe) fluoromethylketone (Z
      VAD.FMK). These peptide analogues were potent inhibitors of CPP32-like protease
      activity in lysates. Pretreatment of hepatocytes with cycloheximide also blocked
      TGF-beta1-induced apoptosis and the increase in CPP32-like activity. Unlike Z
      VAD.FMK and Z-DEVD.FMK, cycloheximide did not inhibit CPP32-like protease
      activity in cell lysates. Thus, cycloheximide may block apoptosis by inhibiting
      the synthesis of a protein, which is involved in the upstream events responsible
      for the activation of the CPP32-like protease activity. Our studies have
      identified two of the CPP32-like proteases, namely CPP32 and Mch3alpha, which are
      activated during the execution phase of hepatocyte apoptosis.

PMID- 9185779
TI  - A mutation in the human canalicular multispecific organic anion transporter gene
      causes the Dubin-Johnson syndrome.
AB  - The human Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver
      disorder characterized by chronic conjugated hyperbilirubinemia. Patients have
      impaired hepatobiliary transport of non-bile salt organic anions. A highly
      similar phenotype has been described for a mutant Wistar rat strain, the
      transport-deficient (TR-) rat, which is defective in the canalicular
      multispecific organic anion transporter (cmoat). This protein mediates adenosine
      triphosphate-dependent transport of a broad range of endogenous and xenobiotic
      compounds across the (apical) canalicular membrane of the hepatocyte. The
      complementary DNA (cDNA) encoding rat cmoat has recently been cloned, and the
      mutation underlying the defect in TR- rats has been identified. In the present
      study, we have isolated the human homologue of rat cmoat, human cMOAT, and
      analyzed the corresponding cDNA from fibroblasts of a DJS patient for mutations.
      Our results show that a mutation in this gene is the cause of DJS.

PMID- 9185780
TI  - Innovative indications for tips.

PMID- 9185781
TI  - Pitfall in the implication of intercellular adhesion molecule-1 expression on
      isolated hepatocytes.

PMID- 9185782
TI  - HBV precore mutants and response to interferon.

PMID- 9185783
TI  - Fialuridine toxicity.

PMID- 9185785
TI  - Researchers struggle with trials of stem-cell transplants for breast cancer.

PMID- 9185786
TI  - Lung volume reduction surgery puts a new twist on an old technique.

PMID- 9185787
TI  - Evaluating estrogen for Alzheimer disease poses ethical and logistical
      challenges.

PMID- 9185788
TI  - Clinical trial investigators talk about getting the data.

PMID- 9185789
TI  - From the Centers for Disease Control and Prevention. Update: outbreaks of
      cyclosporiasis--United States, 1997.

PMID- 9185790
TI  - Addiction medicine.

PMID- 9185791
TI  - Anesthesiology.

PMID- 9185792
TI  - Cardiothoracic surgery.

PMID- 9185793
TI  - Cardiovascular disease.

PMID- 9185794
TI  - Critical care medicine.

PMID- 9185795
TI  - Dermatology.

PMID- 9185796
TI  - Economics.

PMID- 9185797
TI  - Emergency medicine.

PMID- 9185798
TI  - End-of-life care.

PMID- 9185799
TI  - Ethics.

PMID- 9185801
TI  - Gastroenterology and hepatology.

PMID- 9185800
TI  - Family medicine.

PMID- 9185802
TI  - General internal medicine.

PMID- 9185803
TI  - General surgery.

PMID- 9185804
TI  - Geriatric medicine.

PMID- 9185805
TI  - Infectious diseases.

PMID- 9185806
TI  - Law and medicine.

PMID- 9185807
TI  - Medical genetics.

PMID- 9185808
TI  - Medical informatics.

PMID- 9185809
TI  - Nephrology.

PMID- 9185810
TI  - Neurology.

PMID- 9185811
TI  - Nuclear medicine.

PMID- 9185812
TI  - Nutrition.

PMID- 9185813
TI  - Obstetrics and gynecology.

PMID- 9185814
TI  - Oncology.

PMID- 9185815
TI  - Ophthalmology.

PMID- 9185817
TI  - Otolaryngology-head and neck surgery.

PMID- 9185816
TI  - Orthopedics.

PMID- 9185818
TI  - Pathology and laboratory medicine.

PMID- 9185819
TI  - Pediatrics and adolescent medicine.

PMID- 9185820
TI  - Physical medicine and rehabilitation.

PMID- 9185821
TI  - Psychiatry.

PMID- 9185822
TI  - Public health and preventive medicine.

PMID- 9185823
TI  - Quality of care.

PMID- 9185824
TI  - Radiology.

PMID- 9185825
TI  - Rheumatology.

PMID- 9185826
TI  - Sports medicine.

PMID- 9185827
TI  - Transplantation.

PMID- 9185828
TI  - Urology.

PMID- 9185829
TI  - Antiparkinsonian and other motor effects of flupirtine alone and in combination
      with dopaminergic drugs.
AB  - In this study we attempted to specify the behavioural profile of the analgesic
      flupirtine (1, 10 and 20 mg/kg p.o.) in the rat with respect to (i) its
      antiparkinsonian potential alone and as an adjunct to L-dihydroxyphenylalanine (L
      DOPA) in the haloperidol-induced catalepsy (0.5 mg/kg haloperidol i.p.), (ii)
      locomotion and exploratory behaviour in the open field with holeboard, and (iii)
      possible psychomotor stimulating effects in the experimental chamber. In the two
      latter tests, behaviour was additionally challenged by D-amphetamine (2 mg/kg
      i.p.). In the catalepsy tests (horizontal bar, podium, grid) flupirtine alone was
      anticataleptic at doses of 10 and 20 mg/kg p.o., and the antiparkinsonian
      potential of a subthreshold dose of L-DOPA (50 mg/kg p.o.) was potentiated by 1
      and 10 mg/kg p.o. flupirtine. On spontaneous forward locomotion in the open field
      with holeboard, flupirtine (1 and 10 mg/kg p.o.) had no marked effect but
      increased the frequency and duration of head dips, indicative for augmenting
      exploratory behaviour. Spontaneous rearing was reduced and D-amphetamine-induced
      rearing was enhanced by 1 mg/kg p.o. flupirtine. Grooming was reduced by 1 and 10
      mg/kg p.o. flupirtine. In contrast, turning and grooming behaviour (spontaneous
      as well as D-amphetamine-induced) was not markedly influenced by flupirtine in
      the experimental chamber. Sniffing was increased in this test by 1 mg/kg p.o.
      flupirtine but not by the higher dose. Flupirtine is highly effective in
      antagonising neuroleptic-induced catalepsy as well as in potentiating L-DOPA
      treatment in the rat, suggesting it is a prospective new candidate for the
      therapy of Parkinson's disease.

PMID- 9185830
TI  - Time window of infarct reduction by intravenous basic fibroblast growth factor in
      focal cerebral ischemia.
AB  - Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide with
      potent trophic and protective effects on brain neurons, glia and endothelia. In
      previous studies, we showed that intravenously administered bFGF reduced the
      volume of cerebral infarcts following permanent occlusion of the middle cerebral
      artery in rats. In the current study, we examined the time dependence of bFGF
      infusion on infarct reduction, and the effect of co-infusion of bFGF with
      heparin. We found a significant reduction in infarct volume when the bFGF
      infusion (50 microg/kg per h for 3 h) was begun up to 3 h, but not 4 h after the
      onset of ischemia. The infarct reducing effects of bFGF were not altered by co
      infusion of heparin. These results are potentially important in light of the
      ongoing clinical trials of intravenous bFGF in acute stroke.

PMID- 9185831
TI  - Beneficial effects of dantrolene on lipopolysaccharide-induced haemodynamic
      alterations in rats and mortality in mice.
AB  - We investigated the effect of dantrolene, an inhibitor of Ca2+ release from the
      sarcoplasmic reticulum, on the induction of nitric oxide (NO) synthase II by
      bacterial endotoxin (lipopolysaccharide) in the anaesthetised rat and on survival
      in a murine model of severe endotoxaemia. Injection of lipopolysaccharide (i)
      induced biphasic changes of rectal temperature and blood glucose: an initial
      increased phase (< 180 min after injection of lipopolysaccharide) followed by a
      decreased phase (at 240-360 min), (ii) caused a fall in mean arterial blood
      pressure from 115 +/- 3 mmHg (time 0) to 83 +/- 6 mmHg at 360 min, (iii) resulted
      in a substantial hyporeactivity to noradrenaline (1 microg/kg i.v.), (iv) raised
      plasma nitrate (an indicator of NO formation) in a time-dependent manner, (v)
      elicited a significant increase in NO synthase II activity in the lung and (vi)
      caused a 80% lethality (in mice). Pretreatment of animals with dantrolene not
      only attenuated the delayed circulatory failure, but also prevented the
      overproduction of NO and the induction of NO synthase II caused by
      lipopolysaccharide in the rat, and improved survival in a murine model of severe
      endotoxaemia. Thus, dantrolene has beneficial haemodynamic effects in animals
      with endotoxin shock. We propose that a decrease of free cytosolic Ca2+ levels
      plays an important role in the prevention of NO synthase II induction.

PMID- 9185833
TI  - Negative inotropic effect of heparin on tension development in rat skinned
      skeletal muscle fibres.
AB  - Heparin inhibits inositol trisphosphate receptors, particularly in smooth muscle,
      but its effect on skeletal muscle is controversial. Our study showed that heparin
      induced a decrease in the amplitude of 10 mM caffeine-induced contracture in slow
      and fast saponin-skinned fibres. Moreover, measurements on Triton X-100-skinned
      fibres in soleus muscle showed that heparin alone decreased maximal Ca2(+)
      activated tension and Ca2+ sensitivity of contractile proteins, whereas no
      significant effect was observed in extensor digitorum longus muscle. However, in
      the presence of caffeine, heparin decreased maximal Ca2(+)-activated tension in
      both muscles. It would appear that the heparin-induced decrease in the amplitude
      of caffeine contracture in rat skeletal muscle was not related to a direct
      inhibition of Ca2+ release from sarcoplasmic reticulum but to a desensitising
      effect of heparin and caffeine on myofilaments.

PMID- 9185832
TI  - Analysis of alpha1-adrenoceptors in rabbit lower urinary tract and mesenteric
      artery.
AB  - In this study, we have investigated the effects of a series of alpha1
      adrenoceptor antagonists on the phenylephrine-mediated contractions of rabbit
      isolated prostate, urethra, trigone and mesenteric artery. With the exception of
      RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha,alpha-dim ethyl
      1 H-indole-3-ethanamine hydrochloride), the antagonists displayed the lowest
      potency in the urethra. Catecholamine uptake1 and uptake2 appeared not to be the
      cause for the low pK(B)/pA2 values obtained in the urethra because cocaine and
      corticosterone had no effect on the potency of phenylephrine in this tissue. The
      low potencies displayed by prazosin. RS-17053 and HV723 (alpha-ethyl-3,4,5
      trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)amino )propyl)benzene
      acetonitrile fumarate) suggest that the functional receptors in all four tissues
      belong to the alpha(1L)-adrenoceptor class. Whether or not the significant
      between-tissue differences in antagonist potencies are due to heterogeneity of
      this receptor class remains to be elucidated.

PMID- 9185834
TI  - Inhibition of contractions by tricyclic antidepressants and xylamine in rat vas
      deferens.
AB  - The effects of noradrenaline uptake inhibitors on contractions evoked by electric
      field stimulation, noradrenaline, clonidine. 5-hydroxytryptamine, ATP, high K+,
      and BaCl2 in the epididymal half of rat isolated vas deferens were examined.
      Protriptyline, amitriptyline and xylamine concentration-dependently inhibited
      monophasic contractions induced by low frequency electrical stimulation (0.3 Hz,
      1 ms duration, 60 V). Protriptyline and xylamine inhibited in a noncompetitive
      manner the contractile response induced by noradrenaline (3 x 10(-8)-3 x 10(-5)
      M) and the inhibitory effect of protriptyline was reversible, while xylamine
      produced long-lasting inhibition. All three noradrenaline uptake blockers
      inhibited the clonidine (3 x 10(-6) M) or 5-hydroxytryptamine (10(-5) M)-induced
      contraction. Protriptyline and amitriptyline at concentrations of 3 x 10(-6)-3 x
      10(-5) M reversibly inhibited the ATP (10(-4) M)-induced monophasic contraction.
      In contrast, xylamine ((1-3) x 10(-5) M) had no effect. Protriptyline and
      amitriptyline but not xylamine concentration-dependently reduced the high K+ (6 x
      10(-2) M)-induced sustained contraction with respective IC50 values of 1.81 x 10(
      6) M and 8.6 x 10(-7) M. Protriptyline and amitriptyline at 10(-5) M reversibly
      inhibited BaCl2 (3 x 10(-3) M)-induced phasic contractions and xylamine (10(-5)
      M) had no effect. These findings demonstrate that tricyclic antidepressants might
      exert direct inhibitory action on mechanical contraction pathway, whilst
      xylamine, a structurally different inhibitor of noradrenaline uptake, may act
      mainly at alpha-adrenoceptors and other amine receptors on the smooth muscle of
      the rat vas deferens as a long-lasting nonselective antagonist, and it at least
      in part blocks sympathetic transmission.

PMID- 9185835
TI  - Histamine H3 receptors do not modulate reflex-evoked peristaltic motility in the
      isolated guinea-pig ileum.
AB  - We investigated the role played by histamine H3 receptors in the control of
      intestinal peristalsis, using two different in vitro preparations of guinea-pig
      ileum. (a) Ileal segments were perfused from the oral end, inducing peristaltic
      movements (emptying waves), due to the activation of intramural reflexes. Such
      peristaltic motility was measured as changes in the perfusion pressure during the
      emptying phase and the threshold pressure for triggering the emptying wave was
      determined. (b) Ileal segments were mounted horizontally and circular muscle
      contraction evoked by the ascending peristaltic reflex was triggered by caudal
      distension of the intestinal wall. In perfused ileal segments, specific agonists
      acting at histamine H3 receptors, ((R)-alpha-methylhistamine and immepip, 1 nmol
      10 micromol/l), did not cause any change in the threshold pressure for triggering
      the peristaltic wave, or in the rise of the perfusion pressure during the
      emptying phase. Similarly, circular muscle contractions evoked by caudal
      distension of the wall were not affected by these histamine H3 receptor agonists
      up to 10 micromol/l. In the same conditions, a complete inhibition of peristaltic
      movements was elicited by agonists acting at alpha2-adrenoceptors or adenosine A1
      receptors (compound UK 14,304 and N6-cyclopentyladenosine, respectively), their
      effects being prevented by the respective receptor antagonists, idazoxan and 8
      cyclopentyl-1,3-dimethyl-xanthine. These data demonstrate that, contrary to
      alpha2-adrenoceptors and adenosine A1 receptors, histamine H3 receptors are not
      primarily involved in the modulation of intramural reflexes that modulate the
      peristaltic motility of the isolated guinea-pig ileum.

PMID- 9185836
TI  - Bronchoprotective effects of KF-19514 and cilostazol in guinea pigs in vivo.
AB  - It has been shown that inhibitors of cyclic nucleotide phosphodiesterase III and
      IV have a bronchodilator effect. We compared the effects of a selective
      phosphodiesterase III inhibitor, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4
      dihydro-2(1H)-quin olinone (cilostazol) and a phosphodiesterase I/IV inhibitor, 5
      phenyl-3-(3-pyridil) methyl-3H-imidazo[4,5-c][1,8]naphthyridin-4(5H)-one (KF
      19514) on antigen- and histamine-induced bronchoconstriction in guinea pigs in
      vivo. Intravenous administration of cilostazol and KF-19514 inhibited histamine-
      and antigen-induced bronchoconstriction in a dose-dependent manner. When
      assessing the resulting ED50 values, the activity of KF-19514 against antigen
      induced bronchoconstriction was stronger than its antagonism of histamine-induced
      bronchoconstriction (0.004 vs. 0.056 mg/kg). while those of cilostazol were
      contrary (0.835 vs. 0.031 mg/kg). These results suggest that although both
      inhibitors of phosphodiesterase III and phosphodiesterase IV have a
      bronchodilator or bronchoprotective effect, phosphodiesterase IV inhibitors such
      as KF-19514 may be more useful for asthma treatment because KF-19514 had an anti
      allergic effect in addition to the functional bronchodilator activity.

PMID- 9185837
TI  - Increase in gap junction conductance by an antiarrhythmic peptide.
AB  - Impaired cellular coupling is thought to be a very important factor for the
      genesis of cardiac arrhythmia. Cellular coupling is mediated by gap junctions.
      However, there are no therapeutic agents or experimental substances yet that
      increase cellular coupling. In addition, it has been shown that most
      antiarrhythmic drugs available now possess serious adverse effects. Thus, there
      is an urgent need for new antiarrhythmic agents. Previous studies using
      epicardial mapping in isolated rabbit hearts provided indirect evidence
      supporting the hypothesis that a newly synthesised antiarrhythmic peptide (Gly
      Ala-Gly-4Hyp-Pro-Tyr-CONH2 = AAP10) might act via an increase in cellular, i.e.,
      gap junctional coupling. The aim of the present study was to test this
      hypothesis. Measurement of the stimulus-response interval in papillary muscle
      showed a decrease of about 10% after application of 1 microM AAP10. These results
      are compatible with the hypothesis of AAP10 acting on gap junctions. In order to
      prove this hypothesis, gap junction conductance was measured directly by
      performing double-cell voltage-clamp experiments in isolated pairs of guinea-pig
      myocytes. During a 10 min control period gap junction conductance slowly
      decreased with a rate of -2.5 +/- 2.0 nS/min. After application of 10 nM AAP10
      this behaviour reversed and gap junction conductance now increased with +1.0 +/-
      0.7 nS/min. Upon washout of AAP10 gap junction conductance again decreased with a
      rate similar to that under control conditions. Another important finding was that
      we could not detect any other actions of AAP10 on cardiac myocytes. All
      parameters of the transmembrane action potential remained unchanged and,
      similarly, no changes in the IV relationship of single cardiac myocytes treated
      with 10 nM AAP10 could be observed. We conclude that AAP10 increases gap junction
      conductance, i.e., cellular coupling in the heart. This finding might be the
      first step towards the development of a new class of antiarrhythmic agents.

PMID- 9185838
TI  - Human lung mast cells release small amounts of interleukin-4 and tumour necrosis
      factor-alpha in response to stimulation by anti-IgE and stem cell factor.
AB  - Recent reports have suggested that mast cells are capable of producing and
      releasing a number of pro-inflammatory cytokines. However, these studies have
      mainly been carried out using murine tissue culture derived mast cells and it is
      known that these cells differ markedly in their functional properties from
      isolated human mast cells. It was therefore essential to study the release of
      cytokines from the latter cell type. On immunological stimulation with anti
      immunoglobulin E (anti-IgE) or stem cell factor (SCF), purified human lung mast
      cells released, within 2-10 min, small amounts of tumour necrosis factor-alpha
      (10.5 +/- 2.9 pg/10(6) mast cells and 17.9 +/- 7.9 pg/10(6) mast cells,
      respectively) and interleukin-4 (5.3 +/- 2.5 pg/10(6) mast cells and 8.0 +/- 3.2
      pg/10(6) mast cells, respectively). After longer periods of activation (30 min-4
      h). the amounts of cytokines released from stimulated cells decreased to levels
      which were below those of the unstimulated cells. This possible degradation of
      cytokines by mast cells could not be prevented by the addition of protease
      inhibitors.

PMID- 9185839
TI  - [3H]R-terazosin binds selectively to alpha1-adrenoceptors over alpha2
      adrenoceptors - comparison with racemic [3H]terazosin and [3H]prazosin.
AB  - Most tissue sources for adrenoceptors contain a mixed population of alpha1-
      and/or alpha2-adrenoceptor subtypes; thus studies using non-specific radioligands
      are complicated by receptor heterogeneity. The examination of alpha1-adrenoceptor
      radioligand binding by radiolabeled terazosin and its enantiomers was simplified
      by using mouse fibroblast cells, which are thymidine kinase mutant (LTK-),
      transfected with cloned alpha1a-, alpha1b-, and alpha1d-adrenoceptor subtypes.
      [3H]Terazosin and its enantiomers were equipotent at the alpha1b-adrenoceptor.
      [3H]R-Terazosin was significantly less potent than [3H]terazosin and [3H]S
      terazosin at the alpha1a- and the alpha1d-adrenoceptors. Using tissue derived
      alpha-adrenoceptors prepared in cold 25 mM glycyl-glycine buffer, [3H]prazosin,
      [3H]terazosin and [3H]S-terazosin bound to two sites in the rat neonatal lung
      preparation consistent with the presence of both alpha1- and alpha2B
      adrenoceptors. The relative binding potencies of these radioligands at these two
      sites correlated with low affinity binding to the alpha2B-adrenoceptor and high
      affinity binding to an alpha1-adrenoceptor. [3H]R-Terazosin, on the other hand,
      bound to a single site in the rat neonatal lung membrane preparation, most likely
      an alpha1-adrenoceptor. Thus, [3H]R-terazosin may be useful as a selective alpha1
      adrenoceptor radioligand for establishing the functional role of adrenoceptors in
      tissues expressing multiple subtypes.

PMID- 9185840
TI  - Proliferation of adult rat hepatocytes in primary culture induced by insulin is
      potentiated by cAMP-elevating agents.
AB  - We investigated whether or not insulin and cAMP-elevating agents induce the
      proliferation of adult rat hepatocytes during the early and late phases of
      primary culture. Adult rat hepatocytes synthesized a significant amount of DNA
      when cultured in the presence of 10(-7) M insulin for 3 h. Under these
      conditions, the number of nuclei increased within 4 h. Hepatocyte DNA synthesis
      and proliferation were not essentially affected by the initial plating densities.
      Other cAMP-elevating agents, such as glucagon, forskolin and dibutyryl cAMP, as
      well as beta-adrenoceptor agonists (i.e., metaproterenol and isoproterenol) alone
      had no effect on either hepatocyte DNA synthesis or proliferation in primary
      culture. In contrast, these agents potentiated both processes at concentrations
      as low as 10(-7) M when cultured in combination with 10(-7) M insulin. The
      stimulatory effects of beta-adrenoceptor agonists and other cAMP-elevating agents
      were significantly blocked by the cAMP-dependent protein kinase inhibitor, H-89
      (N-[2-(p-(bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride;
      10(-7) M). The mitogenic effect of insulin upon hepatocytes was almost completely
      suppressed by genistein (5 x 10(-6) M), wortmannin (10(-7) M) and by rapamycin
      (10 ng/ml). These results show that insulin rapidly induced the proliferation of
      adult rat hepatocytes in primary culture. The mitogenic effects of insulin were
      potentiated by beta-adrenoceptor agonists and cAMP-elevating agents. The effects
      of beta-adrenoceptor agonists and cAMP-elevating agents may be mediated through
      cAMP-dependent protein kinase. In addition, the activation of receptor tyrosine
      kinase, phosphoinositide 3-kinase and p70 ribosomal protein S6 kinase may be
      involved in the insulin signal transduction pathway.

PMID- 9185841
TI  - Inhibition of hippocampal acetylcholine release by cannabinoids: reversal by SR
      141716A.
AB  - Two synthetic cannabinoids, WIN 55,212-2 {R-(+)-(2,3-dihydro-5-methyl-3-[{4
      morpholinylmethyl]pyrol [1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl)methanone
      monomethanesulfonate} (5.0 and 10 mg/kg i.p.) and CP 55,940 {[1a,2-(R)-5-(1.1
      dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-phenol} {[1a,2-(R)-5
      (1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-phenol} (0.5
      and 1.0 mg/kg i.p.), inhibited acetylcholine release in the rat hippocampus. The
      inhibition was prevented by the cannabinoid receptor antagonist, SR 141716A {N
      (piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide} HCl, at the dose of 0.1 mg/kg i.p. Higher doses of SR 141716A (1.0
      and 3.0 mg/kg i.p.) themselves increased hippocampal acetylcholine release,
      suggesting that acetylcholine output is tonically inhibited by endogenous
      cannabinoids. The results also suggest that the negative effects of marijuana on
      learning and memory may depend on cannabinoid receptor-mediated inhibition of
      acetylcholine release.

PMID- 9185842
TI  - Versatile vectors for direct cloning and ligation-independent cloning of PCR
      amplified fragments for surface display on filamentous bacteriophages.
AB  - We have constructed phagemid and phage-based vectors which can be used for both
      direct (T/A) and ligation-independent cloning (LIC) of PCR products for surface
      display of encoded peptides/proteins fused with the gIII protein of the
      filamentous bacteriophages M13 and fd-tet. The vectors harbour a DNA cassette
      consisting of the lacZ alpha fragment inserted between the +2 and +3 codons of
      gIIIp. The lacZ alpha fragment is flanked by several restriction enzyme
      recognition sites which can be used for conventional blunt- and cohesive-end
      cloning in addition to T/A cloning and LIC. The cloning strategies lead to the
      loss of the lacZ alpha fragment facilitating the selection of the recombinants in
      XGal plates. The efficiency of direct (T/A) cloning and LIC for surface display
      in both vectors was evaluated using PCR-amplified fragments encoding a variety of
      different proteins which included the Fc-binding domain of protein A, the ADP
      ribosylation domain of Pseudomonas exotoxin A and a single-chain antibody
      fragment. The cloning efficiency obtained was 75-85% using the two strategies as
      monitored by restriction enzyme analysis of the recombinant white colonies on
      XGal plates. The expression of encoded proteins in recombinants, which were
      displayed as gIIIp fusions, was found to be 10% in case of T/A cloning but more
      than 90% in case of LIC.

PMID- 9185843
TI  - An artificial regulatory circuit for stable expression of DNA-binding proteins in
      a T7 expression system.
AB  - We had earlier overproduced the transcription activator protein C of
      bacteriophage Mu in a phage-T7 expression system. Although we achieved a high
      level of overproduction, the expression was not consistent. This could be due to
      the leaky expression of T7 RNA polymerase in the uninduced state. Introduction of
      pLysS, a plasmid encoding T7 lysozyme, a natural inhibitor of T7 RNA polymerase,
      resulted in consistent, but extremely low production of the C protein. To
      overcome this problem, we have devised an artificial regulatory circuit to obtain
      stabilised, consistent overproduction of C protein. The C-binding site was cloned
      downstream from the transcription start point of T7 lys. Upon induction, the C
      protein produced binds to its site with a very high affinity, possibly acting as
      a transcriptional roadblock for lys. This would overcome the inhibitory effect of
      T7 lysozyme on T7 RNA polymerase.

PMID- 9185844
TI  - Polypurine/polypyrimidine sequences as cis-acting transcriptional regulators.
AB  - Genome sequence information has generated increasing evidence for the claim that
      repetitive DNA sequences present within and around genes could play a important
      role in the regulation of gene expression. Polypurine/polypyrimidine sequences
      [poly(Pu/Py)] have been observed in the vicinity of promoters and within the
      transcribed regions of many genes. To understand whether such sequences influence
      the level of gene expression, we constructed several prokaryotic and eukaryotic
      expression vectors incorporating poly(Pu/Py) repeats both within and upstream of
      a reporter gene, lacZ (encoding beta-galactosidase), and studied its expression
      in vivo. We find that, in contrast to the situation in Escherichia coli, the
      presence of poly(Pu/Py) sequences within the gene does not significantly inhibit
      gene expression in mammalian cells. On the other hand, the presence of such
      sequences upstream of lacZ leads to a several-fold reduction of gene expression
      in mammalian cells. Similar down-regulation was observed when a structural
      cassette containing poly(Pu/Py) sequences upstream of lacZ was integrated into
      yeast chromosome V. Sequence analysis of the nine totally sequenced yeast
      chromosomes shows that a large number of such sequences occur upstream of ORFs.
      On the basis of our experimental results and DNA sequence analysis, we propose
      that these sequences can function as cis-acting transcriptional regulators.

PMID- 9185845
TI  - Human immunodeficiency virus type-1 p24 sequence from an Indian strain:
      expression in Escherichia coli and implications in diagnostics.
AB  - A 637-bp fragment, corresponding to the p24 human immunodeficiency virus (HIV)
      core protein from the gag ORF, was PCR amplified from DNA isolated from
      peripheral blood mononuclear lymphocytes (PBML) of an asymptomatic HIV-1
      seropositive human subject from Bombay and cloned into PCRScript SK(+). The
      nucleotide sequence revealed highest homology (98.6%) with the consensus sequence
      of the HIV-1 B subtype. The 637-bp KpnI-HindIII fragment was cloned downstream
      from a His6 tag in the pQE30 vector under the control of phage T5 promoter
      leading to production of a 6XHis-p24 fusion protein in Escherichia coli. It
      showed an approx. 24-kDa band by SDS-PAGE. The recombinant p24 reacted with serum
      samples from HIV-infected subjects when tested by Western blot and ELISA.

PMID- 9185846
TI  - Overproduction of fungal ribotoxin alpha-sarcin in Escherichia coli: generation
      of an active immunotoxin.
AB  - alpha-Sarcin is a ribonucleolytic protein secreted by the mold Aspergillus
      giganteus. DNA encoding alpha-sarcin was isolated from the host and cloned into
      T7 promoter based E. coli expression vectors. Using bacterial outer membrane
      protein A (OmpA) signal sequence, properly processed recombinant (re-) protein
      was secreted into the culture medium while in the absence of a signal sequence
      protein remained insoluble in the bacterial inclusion bodies. The re-alpha-sarcin
      was purified to homogeneity by simple chromatographic techniques both from the
      insoluble and soluble sources with respective yields of 40-50 microg/ml and 2-3
      microg/ml. The re-ribotoxin was functionally as active as the native toxin and
      preserved its specificity. The re-alpha-sarcin was used in the construction of an
      active immunotoxin targeted at the human cancer cells overexpressing transferrin
      receptor (TFR).

PMID- 9185847
TI  - Construction of shuttle vectors for genetic manipulation and molecular analysis
      of mycobacteria.
AB  - Two novel shuttle vectors for mycobacteria are described which have been derived
      from the expression system pSD5 developed in our laboratory. Plasmid pSD5B is a
      promoter-selection vector containing a promoterless lacZ gene and allows the
      identification of mycobacterial promoters by the blue colour of the colonies on
      solid media containing XGal. Moreover, the chronological order of appearance of
      blue colonies and intensity of colour provide a qualitative index of
      transcriptional strengths of the cloned promoters. Plasmid pSD5C has been
      designed to construct mycobacterial genomic libraries and express the cloned DNA
      inserts as fusion proteins with maltose binding protein in mycobacteria.
      Libraries in pSD5C provide feasibility for their screening with either DNA probes
      or specific antisera for identifying the genes of interest and for isolation of
      specific genetic loci by complementation of Escherichia coli and mycobacterial
      mutants. These vectors combine the ease of working in E. coli with the advantage
      of directly propagating them in mycobacteria without further manipulations.
      Finally, we demonstrate that these vectors function efficiently both in fast
      growing Mycobacterium smegmatis and slow growing mycobacteria including
      Mycobacterium tuberculosis and Mycobacterium bovis BCG.

PMID- 9185848
TI  - Expression and characterization of Pichia etchellsii beta-glucosidase in
      Escherichia coli.
AB  - The beta-glucosidase enzyme is important as the terminal enzyme involved in
      hydrolysis of cellobiose and short-chain cellodextrins generated during enzymatic
      cellulose degradation. Under controlled reaction conditions the enzyme also
      displays cello-oligosaccharide synthesizing ability (based on either the
      thermodynamic or kinetic approach). We present here the purification of the
      enzyme beta-glucosidase (BGL) of Pichia etchellsii from recombinant pBG55
      Escherichia coli clone. The kinetic parameters, substrate specificity and
      oligosaccharide synthesizing ability of the purified enzyme are also reported.
      The purified 200-kDa protein (tetramer of 50 kDa) was identified as a broad
      substrate-specificity enzyme exhibiting increased temperature and glucose
      tolerance compared to the native yeast enzyme. Temperature directed substrate
      specificity for aryl beta,1-4 linkage, and beta (1-2), beta(1-4), beta(1-6) and
      beta(2-1) linkages in various natural disaccharides was observed. Glycosylation
      of the enzyme was found to be unimportant for enzyme activity. With both
      cellobiose and glucose, oligosaccharide synthesis was detected. The implications
      of this information with regard to cellulose hydrolysis and oligosaccharide
      synthesis are discussed.

PMID- 9185850
TI  - Expression and characterization of the hepatitis E virus ORF3 protein in the
      methylotrophic yeast, Pichia pastoris.
AB  - We have used the methylotrophic yeast, Pichia pastoris, to express the open
      reading frame 3 (ORF3) of the hepatitis E virus (HEV). The ORF3 gene codes for a
      123-amino-acid protein that contains highly immunodominant epitopes and is a
      potentially useful diagnostic and immunoprophylactic antigen. The expressed
      protein showed positive on immunoblots probed against antibodies raised in rabbit
      and infected human patient sera. In order to optimize the ORF3 protein
      expression, we have examined the regulated expression of this protein and
      characterized it. Unlike its expression in E. coli, the ORF3 protein was present
      in both the soluble and insoluble fractions of the cell lysate. The expressed
      protein is not glycosylated and does not undergo any major processing in the host
      strain.

PMID- 9185849
TI  - Strategies for optimal synthesis and secretion of heterologous proteins in the
      methylotrophic yeast Pichia pastoris.
AB  - Numerous heterologous proteins have been produced at greater than gram per liter
      levels in the methylotrophic yeast, Pichia pastoris, using the methanol oxidase
      promoter. The factors that drastically influence protein production in this
      system include: copy number of the expression cassette, site and mode of
      chromosomal integration of the expression cassette, mRNA 5'- and 3'-untranslated
      regions (UTR), translational start codon (AUG) context, A+T composition of cDNA,
      transcriptional and translational blocks, nature of secretion signal, endogenous
      protease activity, host strain physiology, media and growth conditions, and
      fermentation parameters. All these factors should be considered in designing an
      optimal production system. The inherent ability of P. pastoris to convert the
      zymogen (pro-enzyme) form of matrix metalloproteinases (MMP) into active mature
      forms (which tend to self-degrade, and in some instances also cause damage to
      cells), largely limits the use of this system for the production of MMP. However,
      this problem can be partly alleviated by co-expression of tissue inhibitor of MMP
      (TIMP-1).

PMID- 9185851
TI  - Characterisation of 3' end formation of the yeast HIS3 mRNA.
AB  - The nucleotide (nt) sequence of the 3' end of the yeast HIS3 mRNA was determined
      by PCR amplification of the 3' end. Analysis of 28 individual clones revealed
      that at least 13 distinct polyadenylation sites are present. The sites of
      polyadenylation are extremely heterogeneous and do not show any obvious
      similarity other than that they occur after pyrimidine residues in most cases.
      Most mutants carrying internal deletions of the 3' untranslated region (3' UTR)
      did not abolish 3' end formation and showed polyadenylation at normal sites.
      Deletion of a 90-nt region that contains an A+T-rich sequence close to the 3' end
      of the HIS3 coding sequence and a subset of processing sites resulted in a
      drastic reduction in the levels of full-length HIS3 mRNA and concomitant
      transcription past the normal HIS3 3' end. The 90-nt region appears to be
      sufficient to direct the formation of at least a subset of the HIS3 3' ends since
      mutants that carry deletions of flanking regions of this sequence show detectable
      levels of HIS3 mRNA. Spacing between the upstream A-T sequence and the site of
      processing is variable. In the light of the extreme heterogeneity of the sites, a
      possible mechanism for 3' processing is discussed.

PMID- 9185852
TI  - The presence of two tightly bound Zn2+ ions is essential for the structural and
      functional integrity of yeast RNA polymerase II.
AB  - DNA-dependent RNA polymerases (RNApol) are Zn2+ metalloproteins where the Zn2+
      ion plays both catalytic and structural roles. Although the ubiquitous presence
      of Zn2+ with the RNApol from eukaryotes had already been established, the exact
      stoichiometry of Zn2+ ion(s) per mole enzyme is not well documented, and its role
      in enzymatic function remains elusive. We show here that RNApolII from
      Saccharomyces cerevisiae has two Zn2+ ions tightly associated with it which are
      necessary for its transcriptional activity. Upon prolonged dialysis against 10 mM
      EDTA for 4-5 h, the enzyme loses one Zn2+, as well as partial activity. However,
      Zn2+ can be added back to the enzyme, but without recovering its total activity.
      5 mM orthophenanthroline (OP) removes one Zn2+ within 2 h; the enzyme, however,
      cannot be reconstituted back with Zn2+. Circular dichroism (CD) studies showed
      that the conformation of the native enzyme is unique and cannot be reproduced
      with Zn2+-reconstituted RNApolII. Similarly, the rate of abortive synthesis of a
      dinucleotide product over a non-specific template is faster when catalyzed by two
      Zn2+-native enzymes. Zn2+-reconstituted RNApolII or one Zn2+-RNApolII showed a
      slower abortive synthesis rate. 65Zn2+-blotting experiments indicated that the
      removal of one Zn2+ from the enzyme destroys the Zn2+-binding ability of the
      larger subunits of yeast RNApolII. In order to check whether the presence of Zn2+
      ions has any effect on substrate recognition, we followed the binding of (gamma
      AmNS)UTP, a fluorescent substrate analog to RNApolII. It was observed that OP
      treated enzyme showed non-specific substrate recognition, whereas two Zn2+-native
      RNApol binds substrate at a single site.

PMID- 9185853
TI  - Application of yeasts in gene expression studies: a comparison of Saccharomyces
      cerevisiae, Hansenula polymorpha and Kluyveromyces lactis -- a review.
AB  - From the onset of gene technology yeasts have been among the most commonly used
      host cells for the production of heterologous proteins. At the beginning of this
      new development the attention in molecular biology and biotechnology focused on
      the use of the best characterized species, Saccharomyces cerevisiae, leading to
      an increasing number of production systems for recombinant compounds. In recent
      years alternative yeasts became accessible for the techniques of modern molecular
      genetics and, thereby, for potential applications in biotechnology. In this
      respect Kluyveromyces lactis, and the methylotrophs Hansenula polymorpha and
      Pichia pastoris have been proven to offer significant advantages over the
      traditional baker's yeast for the production of certain proteins. In the
      following article, the present status of the various yeast systems is discussed.

PMID- 9185854
TI  - A novel MAP-kinase kinase from Candida albicans.
AB  - A putative MAP-kinase kinase-encoding gene, CaSTE7, was isolated from Candida
      albicans by complementation of ste7 and ste11 mutants of the pheromone signal
      transduction pathway of Saccharomyces cerevisiae. The nucleotide (nt) sequence
      revealed an ORF of 1767 nt encoding a putative protein of 589 amino acids (aa).
      CaSTE7 has a strong homology with MAP-kinase kinase STE7 of S. cerevisiae, the
      kinase domain having 45% homology with that of STE7. The deduced aa sequence
      contained all eleven consensus kinase subdomains found in MAP-kinase kinases. It
      can suppress the mating defect of ste5, ste11, ste7, and fus3 kss1 double
      mutants, but it cannot bypass the ste12 mutation. CaSTE7 behaves as a hyperactive
      allele of STE7, suppressing the mating defects of the pheromone signal
      transduction pathway by constitutively stimulating STE12, and hence STE12
      dependent processes.

PMID- 9185855
TI  - Polypeptides of hepatitis B surface antigen produced in transgenic potato.
AB  - Chimeric genes containing the genomic fragments of hepatitis B virus (HBV) coding
      for middle (M) and major/small (S) surface proteins were constructed and
      expressed in transgenic potato plants under the control of the cauliflower mosaic
      virus 35S promoter. Enzyme-linked immunosorbent assay (ELISA) revealed the
      presence of HBV surface antigen (HBsAg) determinants in extracts from transgenic
      plants carrying both constructions, the pre-S2 determinant was identified using
      the corresponding monoclonal antibodies (mAb) in a dot immunobinding assay.
      Polypeptides of the immunoaffinity-purified S and M proteins were analyzed by
      sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. Two polypeptides of
      the M protein, probably representing different glycosylated forms, and the
      multimeric forms of HBsAg were observed.

PMID- 9185856
TI  - Involvement of host factors in transcription from baculovirus very late promoters
      -- a review.
AB  - The baculovirus expression vector system has emerged as the system of choice for
      the expression of a number of heterologous genes of both prokaryotic and
      eukaryotic origin. This system utilizes the baculovirus very late, hyperactive
      polyhedrin and p10 promoters to drive the transcription of foreign genes.
      Regulation of transcription from these promoters is presently not well understood
      even though a number of viral gene products that may be important for
      transcription have been identified. Fresh insight into host-virus interactions
      during baculovirus pathogenesis is now offered by the identification of insect
      host factors that interact with transcriptionally essential motifs of these
      promoters as well as cis-acting enhancer-like elements upstream from the
      promoter.

PMID- 9185857
TI  - Baculovirus multigene expression vectors and their use for understanding the
      assembly process of architecturally complex virus particles.
AB  - The baculovirus expression vector is a eukaryotic DNA viral vector for the
      cloning and expression of foreign genes in cultured lepidopteran insect cells and
      insects. It has become an important tool for the large-scale production of
      recombinant proteins for a variety of applications including the structure
      function analysis of genes and their gene products. We have developed a number of
      baculovirus multigene expression vectors and utilized these to understand the
      assembly process of multicomponent capsid structures of large viruses such as
      bluetongue virus (BTV), a member of the Orbivirus genus within the family
      Reoviridae. BTV is some 810 A in diameter and comprised of two protein shells
      containing four major proteins, VP2, VP5, VP7 and VP3, surrounding a genome of
      ten double-stranded RNA segments and three minor proteins (VP2, VP4 and VP6). BTV
      is the etiological agent of a sheep disease that is sometimes fatal in certain
      parts of the world (e.g., Africa, Asia, and the Americas). Using baculovirus
      multigene vectors, we have co-expressed various combinations of BTV genes in
      insect cells and produced structures that mimic the various stages of BTV
      assembly. For example, co-expressed VP3 and VP7 form BTV core-like particles,
      while co-expressed VP2, VP5, VP7 and VP3 form BTV virus-like particles. Using
      deletion, point and domain switching analyses of each protein, we have been able
      to identify certain sequences in the VP7 and VP3 proteins that are essential for
      the assembly of core-like particles. These expression and biochemical studies
      have been complemented by collaboration studies using cryo-electron microscopy
      and image processing analyses to provide the three-dimensional structure of the
      expressed particles. In addition and with other associates, we have used X-ray
      crystallography of VP7 to deduce its atomic structure. Extensive studies on the
      immune responses elicited by these self-assembled particles, and chimeric
      derivatives involving various foreign antigens, have been carried out. Finally,
      using as little as 10 microg of the self-assembled virus-like particles, we have
      shown that they can confer long-lasting protection in sheep against BTV.

PMID- 9185858
TI  - Purification and characterization of secreted human leptin produced in
      baculovirus-infected insect cells.
AB  - The product of the human ob (obesity) gene, leptin, appears to function in the
      maintenance of body weight in vivo. When injected into mice, this hormone reduces
      food consumption and causes weight loss. This work has been done with recombinant
      leptin (re-leptin) purified and renatured from inclusion bodies in Escherichia
      coli. We have expressed the human obesity gene encoding the predicted full-length
      leptin in Spodoptera frugiperda (Sf-9) cells by infection with the recombinant
      baculovirus system. Protein corresponding to re-leptin was secreted into the
      culture medium and purified in sufficient quantity for testing biological
      activity. The secreted re-protein was characterized and found to be unmodified
      except for correct cleavage of the signal peptide during export from the cells.
      The resulting molecule is expected to be properly folded and has been purified to
      a high level of homogeneity. The re-leptin secreted from Sf-9 cells should be an
      appropriate source of protein for study of the native structure.

PMID- 9185860
TI  - Expression of lacZ reporter gene under the control of the polyhedrin promoter of
      Spodoptera litura nuclear polyhedrosis virus.
AB  - Promoter function of the putative polyhedrin-encoding gene (polh) of Spodoptera
      litura nuclear polyhedrosis virus (S1MNPV) was determined by transferring it to
      the Autographa californica nuclear polyhedrosis virus (AcMNPV) through the AcNPV
      polh based vector, pVL1393. Three transfer vectors pCBT2, pCBT3 and pCBT4 were
      constructed by substituting the promoter and the neighbouring sequences of AcNPV
      in pVL1393 by that of S1NPV. The Escherichia coli lacZ gene was placed downstream
      from the S1NPV polh promoter in the hybrid transfer vector (pCBT) constructs. Co
      transfection of Spodoptera frugiperda cells (Sf9) with each of the pCBTlacZ
      vector and wild-type AcNPV DNAs led to synthesis of beta-galactosidase (beta
      Gal). The plaque-purified recombinant viruses (S1AcNPV.lacZ) expressing lacZ
      under the polh promoter of S1NPV are stable. The highest beta Gal activity was
      obtained with S1AcNPV4.lacZ. Production of beta Gal with recombinant virus,
      S1AcNPV3.lacZ in which S1NPV polh promoter is in the reverse orientation in the
      AcNPV genome, is 83% of that produced by S1AcNPV4.lacZ. These results indicate
      that the S1NPV polh promoter is active in the genetic environment of AcNPV; the
      polh of S1NPV is phylogenetically related to AcNPV like other baculoviruses.

PMID- 9185859
TI  - Production of a urokinase plasminogen activator-IgG fusion protein (uPA-IgG) in
      the baculovirus expression system.
AB  - Numerous studies have demonstrated the importance of urokinase plasminogen
      activator (uPA) and its receptor, uPAR, in the processes of tumor progression and
      metastasis. Thus, the uPA/uPAR interaction may represent an important target for
      inhibiting metastatic disease. The baculovirus expression system was used to
      produce high levels of a secreted uPA-Immunoglobulin G fusion protein (uPA-IgG)
      which could then be used for displacing uPA from the surface of tumor cells. The
      recombinant uPA-IgG fusion protein was placed under the control of either the
      viral polyhedrin promoter or a copy of the viral basic protein promoter.
      Recombinant viruses were then used to infect Sf9 and BTI-Tn-5B1-4 cells.
      Infection of both cell types resulted in the production of secreted uPA-IgG. The
      molecular mass of the secreted protein as determined by SDS-PAGE was
      approximately 40 kDa. The highest level of secreted uPA-IgG, 444 microg/ml, was
      found in the culture medium of BTI-Tn-5B1-4 cells 72 h post-infection with the
      basic protein promoter-uPA-IgG virus. In the case of Sf9 cells, the highest level
      of secreted protein was 195 microg/ml. The amount of cell-associated uPA-IgG in
      infected BTI-Tn-5B1-4 cells was significantly less than that of infected Sf9
      cells, reflecting the superior secretory capability of the BTI-Tn-5B1-4 cells.
      The uPA-IgG was readily purified using a combination of zinc chelate and
      sephacryl S-100 column chromatography. Routinely, greater than 100 mg of greater
      than 95% pure protein could be obtained per liter of culture medium collected at
      72 h post-infection of BTI-Tn-5B1-4 cells with the basic protein promoter virus.
      BIAcore analysis and competition binding assays using LOX human malignant
      melanoma cells expressing uPAR indicated that the purified recombinant protein
      possessed similar ligand binding characteristics to that of human uPA.

PMID- 9185861
TI  - Development of a functional assay for Ca2+ release activity of IP3R and
      expression of an IP3R gene fragment in the baculovirus-insect cell system.
AB  - Receptor-stimulated phosphoinositide (PI) hydrolysis is an important and
      ubiquitous mechanism of intracellular signaling. Inositol 1,4,5-trisphosphate
      (IP3), generated by phosphoinositide (PI) hydrolysis, binds to and gates an
      intracellular Ca2+ channel, the IP3 receptor (IP3R), which is therefore a central
      component of this signaling cascade. Here we describe the development of a
      baculovirus (BV)/Sf (S. frugiperda) cell system that can be used to look at IP3R
      function. Agonist-evoked changes in intracellular Ca2+ levels [Ca2+]i were
      measured (using Fura2) in Sf cells expressing the gene encoding the muscarinic
      acetylcholine receptor (vm1AchR). Furthermore, we have constructed a recombinant
      BV (vIP3R), with the core of the IP3R ligand-binding domain from the Drosophila
      IP3R, under the polyhedrin promoter. The recombinant protein from such a virus
      was expected to act as a large ligand sink for IP3, generated by stimulation of
      vm1AchR. Cells coinfected with recombinant BV carrying the potential dominant
      negative vIP3R construct and vm1AchR have been used to assay the modulation of
      IP3R-mediated Ca2+ release, by the ligand sink.

PMID- 9185863
TI  - Production and purification of novel secreted human proteins.
AB  - Our objective during the last year was to produce and purify 50-80 novel,
      secreted human proteins identified via high throughput cDNA sequencing and
      computer analysis. We chose the baculovirus expression vector system in order to
      obtain secreted, correctly folded, bioactive proteins. Recombinant (re
      )baculoviruses (BV) were plaque purified, and pulse-labeling was used to verify
      the synthesis and secretion of the re-proteins. N-terminal microsequencing was
      performed to simultaneously confirm the identity of the protein(s) as well as the
      signal peptide (SP) cleavage site(s). Following sequence confirmation, the
      proteins were purified to homogeneity and functional assays carried out to
      determine potential therapeutic applications. We identified proteins with
      antiviral activity, several novel growth factors, proteins influencing the
      differentiation of specific cell types, novel proteases and protease inhibitors
      among others. Certain proteins were expressed both in insect cells and in CHO
      stable cell lines. In the cases analyzed, we found that the same SP cleavage site
      was utilized in the two expression systems. Significant differences were observed
      in the carbohydrate moieties attached to the proteins, though no effects on the
      biological activity due to these differences have been demonstrated. The BV
      system has served as a viable alternative for the high throughput, high fidelity
      expression of many novel secreted human genes. To date, more than 75 new genes
      have been expressed, and the re-proteins purified. This expression system
      combines many favorable traits including relative speed, moderate cost but
      perhaps most importantly, the production of biologically active proteins.

PMID- 9185862
TI  - Novel green fluorescent protein (GFP) baculovirus expression vectors.
AB  - Baculovirus expression vectors were constructed, which contained gfp as a
      reporter gene. Substitutions in the amino acid sequences were carried out to
      produce two mutant forms of GFP. One of these mutants produces blue color when
      excited by ultraviolet (UV) light. The other mutant produces a yellow color that
      can be visualized in regular daylight. The gene of interest cloned in-frame with
      the gfp open reading frame allows visualization of the produced GFP-fusion
      protein using UV light. The presence of an in-frame 6 x His tag between the gfp
      cDNA and the multiple cloning site allows purification of the fusion protein on a
      Ni-NTA (nickel-nitrilo-triacetic acid) agarose matrix.

PMID- 9185864
TI  - Sequencing of the putative DNA helicase-encoding gene of the Bombyx mori nuclear
      polyhedrosis virus and fine-mapping of a region involved in host range expansion.
AB  - The complete sequence of a 3666-nucleotide (nt) open reading frame (ORF) and its
      flanking regions (58.1-62.1 map units (m.u.) from Bombyx mori nuclear
      polyhedrosis virus (BmNPV)) was determined. This ORF, BmNPV dnahel, encoded a
      predicted protein of 143623 Da which possessed seven consensus motifs found in
      proteins which unwind duplex DNAs, indicating that it is a DNA helicase. A 572-bp
      SacI-HindIII fragment, BmScH, that was previously shown to expand the host range
      of Autographa californica NPV (AcNPV) following homologous recombination [Maeda
      et al. (1993) J. Virol. 67, 6234-6238], was localized within BmNPV dnahel. By
      cotransfection experiments, two adjacent nt (A and T) that appeared to be the
      minimal essential sequence necessary to expand the host range of AcNPV, were
      mapped within BmScH. These adjacent nt encoded a single amino acid difference
      between BmNPV (Asp) and AcNPV (Ser).

PMID- 9185865
TI  - Heterologous promoter recognition leading to high-level expression of cloned
      foreign genes in Bombyx mori cell lines and larvae.
AB  - The baculovirus expression system using the Autographa californica nuclear
      polyhedrosis virus (AcNPV) has been extensively utilized for high-level
      expression of cloned foreign genes, driven by the strong viral promoters of
      polyhedrin (polh) and p10 encoding genes. A parallel system using Bombyx mori
      nuclear polyhedrosis virus (BmNPV) is much less exploited because the choice and
      variety of BmNPV-based transfer vectors are limited. Using a transient expression
      assay, we have demonstrated here that the heterologous promoters of the very late
      genes polh and p10 from AcNPV function as efficiently in BmN cells as the BmNPV
      promoters. The location of the cloned foreign gene with respect to the promoter
      sequences was critical for achieving the highest levels of expression, following
      the order + 35 > + 1 > -3 > -8 nucleotides (nt) with respect to the polh or p10
      start codons. We have successfully generated recombinant BmNPV harboring AcNPV
      promoters by homeologous recombination between AcNPV-based transfer vectors and
      BmNPV genomic DNA. Infection of BmN cell lines with recombinant BmNPV showed a
      temporal expression pattern, reaching very high levels in 60-72 h post infection.
      The recombinant BmNPV harboring the firefly luciferase-encoding gene under the
      control of AcNPV polh or p10 promoters, on infection of the silkworm larvae led
      to the synthesis of large quantities of luciferase. Such larvae emanated
      significant luminiscence instantaneously on administration of the substrate
      luciferin resulting in 'glowing silkworms'. The virus-infected larvae continued
      to glow for several hours and revealed the most abundant distribution of virus in
      the fat bodies. In larval expression also, the highest levels were achieved when
      the reporter gene was located at + 35 nt of the polh.

PMID- 9185866
TI  - Alphavirus expression vectors and their use as recombinant vaccines: a
      minireview.
AB  - Alphavirus vectors have become widely used in basic research to study the
      structure and function of proteins and for protein production purposes.
      Development of a variety of vectors has made it possible to deliver foreign
      sequences as naked RNA or DNA, or as suicide virus particles produced using
      helper vector strategies. Preliminary reports also suggest that these vectors may
      be useful for in vivo applications where transient, high-level protein expression
      is desired, such as recombinant vaccines. The initial studies have already shown
      that alphavirus vaccines can induce strong humoral and cellular immune responses
      with good immunological memory and protective effects.

PMID- 9185867
TI  - Recombinant adenovirus synthesizing cell surface-anchored beta hCG induces
      bioneutralizing antibodies in rats.
AB  - A recombinant adenovirus (re-Ad) has been constructed that synthesizes a cell
      surface-anchored form of the beta-subunit of human chorionic gonadotropin (beta
      hCG). This was achieved by in-frame fusion of beta hCG cDNA at its C terminus
      with the gene sequences coding for the vesicular stomatitis virus glycoprotein
      (VSVg) transmembrane domain. The fusion protein gene was placed under the control
      of human cytomegalovirus (hCMV) immediate early promoter and this expression
      cassette was inserted into the E1 region of Ad type 5 by homologous
      recombination. In vitro experiments using re-Ad-infected 293 cells showed that
      beta hCG fusion protein was made as early as 6 h post infection and the protein
      was anchored to the cell membrane as seen by immunofluorescence staining. The re
      Ad induced bioneutralizing antibodies (Ab) to hCG when inoculated in rats through
      intraperitoneal or intramuscular routes. The Ab were made in a dose-dependent
      manner. However, orally delivered re-Ad failed to generate any significant immune
      response.

PMID- 9185868
TI  - Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and
      expression of transduced sequences in mice.
AB  - Adeno-associated virus 2 (AAV), a non-pathogenic human parvovirus, is gaining
      attention as a vector for its potential use in human gene therapy. However, few
      studies have examined the safety and the efficacy of this vector system in vivo.
      We report here that recombinant AAV vectors, when directly injected intravenously
      in mice, accumulated predominantly in liver cells, suggesting that AAV may
      possess in vivo organ-tropism for liver. The transduced lacZ reporter gene was
      expressed in hepatocytes in the liver and, at the level examined, did not appear
      to induce any detectable cytotoxic T lymphocyte response against beta Gal. AAV
      mediated transduction of murine hematopoietic progenitor cells ex vivo followed
      by transplantation into lethally irradiated syngeneic mice also revealed high
      efficiency gene transfer into progeny cells without any observable cytotoxicity
      or deleterious effect. The transduced reporter gene sequences were also expressed
      in mice in vivo. The AAV-based vectors may thus prove useful as a potentially
      safe alternative to the more commonly used retrovirus- and adenovirus-based
      vector systems.

PMID- 9185869
TI  - Generation of effective cancer vaccines genetically engineered to secrete
      cytokines using adenovirus-enhanced transferrinfection (AVET).
AB  - Cancer vaccines are based on the concept that tumors express novel antigens and
      thus differ from their normal tissue counterparts. Such putative tumor-specific
      antigens should be recognizable by the immune system. However, malignant cells
      are of self origin and only poorly immunogenic, which limits their capability to
      induce an anticancer immune response. To overcome this problem, tumor cells have
      been isolated, genetically engineered to secrete cytokine gene products and
      administered as cancer vaccines. We used adenovirus-enhanced transferrinfection
      (AVET), which allows high-level transient transgene expression, to introduce
      cytokine gene expression vectors into murine melanoma cells. The efficiency of
      AVET makes laborious selection and cloning procedures obsolete. We administered
      such modified tumor cells as cancer vaccines to syngeneic animals and
      investigated their impact on the induction of anticancer immunity. We found that
      IL-2 or GM-CSF gene-transfected murine melanoma cells are highly effective
      vaccines. Both of these cytokine-secreting vaccines cured 80% of animals which
      bore a subcutaneous micrometastasis prior to treatment, and induced potent
      antitumor immunity. The generation of antitumor immunity by these cytokine
      secreting vaccines requires three different steps: (1) tumor antigen uptake and
      processing by antigen-presenting cells (APCs) at the site of vaccination; (2)
      migration of these APCs into the regional lymph nodes where T-cell priming
      occurs; (3) recirculation of specific, activated T-cells that recognize distinct
      tumor load and initiate its elimination. Extending our previously reported
      studies, we have now comprehensively analysed the requirements for effective
      antitumor vaccination in animals. This may also become the basis for treatment of
      human cancer patients.

PMID- 9185870
TI  - Non-viral ex vivo hepatic gene transfer by in situ lipofection of liver and
      intraperitoneal transplantation of hepatocytes.
AB  - Perfusion of liver with plasmid DNA-lipofectin complexes via the portal vein
      results in efficient accumulation of the vector in hepatocytes. Such hepatocytes,
      when administered intraperitoneally into a hepatectomized rat, repopulate the
      liver and express the transgene efficiently. This procedure obviates the need for
      large-scale hepatocyte culture for ex vivo gene transfer. Further,
      intraperitoneal transplantation is a simple and cost-effective strategy of
      introducing genetically modified hepatocytes into liver. Thus, in situ
      lipofection of liver and intraperitoneal transfer of hepatocytes can be developed
      into a novel method of non-viral ex vivo gene transfer technique that has
      applications in the treatment of metabolic disorders of liver and hepatic gene
      therapy.

PMID- 9185871
TI  - Multifunctional activities of human fibroblast 34-kDa hyaluronic acid-binding
      protein.
AB  - We have already reported that human fibroblast 34-kDa hyaluronic acid-binding
      protein (HABP) is identical with P32, the protein co-purified with splicing
      factor SF-2 [Deb and Datta (1996) J. Biol. Chem. 271, 2206-2212]. Data search
      further revealed that it has 92% sequence homology with a murine protein YL2
      which interacts with HIV1 Rev. In this paper we have successfully demonstrated
      that HIV1 Rev binds with labeled 34-kDa HABP which can be competed with excess
      unlabeled HABP, suggesting this protein can be a cellular factor promoting HIV1
      Rev to function. Interestingly, the multifunctional nature of HABP has been
      elucidated as it has 100% homology with another protein gC1q, the complement
      protein. The distinct non-overlapping binding motifs for HA and gC1q have been
      identified in the same protein, suggesting that either the protein can function
      independently or its activity is regulated by ligand binding, wherein its binding
      to one of the ligands may modulate the receptor activity of the other ligand.

PMID- 9185872
TI  - Involvement of peritoneal dendritic cells in the induction of autoimmune
      prostatitis.
AB  - We have been working within a model of autoimmune prostatitis induced by the
      intraperitoneal administration of saline extract of rat male accessory glands
      (RAG) associated to liposomes. The intraperitoneal administration of RAG
      liposomes elicits both primary and secondary cellular autoimmune responses to RAG
      as well as organ-specific lesions. To evaluate the participation of dendritic
      cells (DC) in the induction of the autoimmune response, we purified peritoneal DC
      (PDC) after a single injection of RAG-liposomes and we characterized this
      population by morphology and phenotype. Based on adherence and morphologic
      criteria, we determined that PDC comprised approximately 1% of the total
      peritoneal cells. The ultrastructure of the dendritic cell enriched fraction was
      assessed by electron microscopy. By FACS analysis, PDC showed a two to three-fold
      increase in expression of the IA molecule compared to macrophages. They expressed
      low but positive levels of the CD14 marker, and intermediate levels of both CD11b
      (Mac-1) and CD54 (ICAM-1) adhesion molecules. In addition, PDC transferred either
      intravenously or intraperitoneally efficiently elicited the autoimmune response
      to RAG in normal receptors. These results support the involvement of peritoneal
      dendritic cells in the induction of autoimmune prostatitis, modifying the idea of
      macrophages as the single antigen presenting cell in the peritoneal cavity.

PMID- 9185874
TI  - Mapping of SLE-specific Sm B cell epitopes using murine monoclonal antibodies.
AB  - In this study we have used a number of monoclonal antibodies with various anti-Sm
      specificities originating from MRL/lpr mice to map B cell epitopes of the Sm-B/B'
      and Sm-D1 proteins. Selection of Sm-B subfragments reactive with the Sm-B/B'
      specific monoclonal antibody ANA125 from a DNaseI fragment expression library
      revealed that the epitope recognized by this monoclonal antibody is located
      between amino acids 146 and 158: GRGTVAAAAAAAT. The epitopes recognized by two
      distinct Sm-D1-specific monoclonal antibodies, 7.13 and ANA127, appeared to be
      located in the carboxy-terminal region of the protein as revealed by
      immunoprecipitation of in vitro translated deletion mutants of Sm-D1. These
      epitopes are probably identical and not simply composed of a GR repeat, which is
      a characteristic feature of this part of the protein. Immunoprecipitation of in
      vitro translated deletion mutants of both Sm-B and Sm-D1 was also employed to
      determine the sequence requirements for recognition by two monoclonal antibodies
      that are cross-reactive with several Sm proteins, Y12 and ANA128. The epitope
      recognized by these two monoclonal antibodies is probably also identical and
      composed by the juxtaposition of several regions in the folded protein. The low,
      but significant, level of immunoprecipitation of truncated versions of both Sm-B
      and Sm-D1, suggests that the Sm domain, which is shared by all Sm proteins, in
      particular the amino-terminal part of the Sm1 motif of Sm-B and Sm-D1, plays an
      important role in formation of the cross-reactive epitope and might contribute to
      cross-reactivity with other Sm proteins. The results of immunoprecipitation
      experiments with cellular extracts show that the epitopes recognized by all anti
      Sm monoclonal antibodies used in this study are accessible in the assembled
      snRNPs.

PMID- 9185873
TI  - Characterization of estrogen-induced autoantibodies to cardiolipin in non
      autoimmune mice.
AB  - Antibodies to cardiolipin, in humans, have been associated with a variety of
      autoimmune disorders including anti-phospholipid syndrome, systemic lupus
      erythematosus and Sjogren's syndrome. These antibodies have also been
      demonstrated in autoimmune-prone MRL-Mp-lpr/lpr (MRL/lpr), BXSB-Mp-(+yaa) (BXSB)
      and (NZW x BXSB)F1 mice. In previous work, we had shown that gonadectomized or
      intact male and female non-autoimmune C57BL/6 mice, upon treatment with estrogen,
      express autoantibodies to cardiolipin. In this study, we extend these findings
      and show that the expression of these antibodies persists for months even after
      the exposure to exogenous estrogen has been terminated. These antibodies are of
      IgM and IgG, but not IgA, isotypes, and the predominant IgG subisotype is IgG2b.
      Estrogen-induced antibodies to cardiolipin only minimally cross-reacted with DNA,
      actin or ovalbumin. The binding of antibodies to cardiolipin from autoimmune
      human patients in general has been shown to depend upon the presence of a
      cofactor, beta2-glycoprotein I. We found that in estrogen-treated C57BL/6 mice,
      as well as in SLE-prone MRL/lpr and BXSB mice, the binding of anti-cardiolipin
      antibodies to cardiolipin was not enhanced, but rather reduced, in the presence
      of human beta2-glycoprotein I. Further, addition of exogenous human beta2
      glycoprotein I to purified immunoglobulin fractions containing anti-cardiolipin
      antibodies reduces, rather than enhances, the binding to cardiolipin. Together,
      these data show that persistent detectable levels of IgG and IgM autoantibodies
      specific for cardiolipin can be induced in normal mice by estrogen treatment
      alone (i.e. without administration of autoantigens). Further, we characterize
      these antibodies regarding their kinetics, cross-reactivity, isotype distribution
      and cofactor (beta2-glycoprotein I) requirements.

PMID- 9185875
TI  - Humoral mechanisms in T cell vaccination: induction and functional
      characterization of anti-lymphocytic autoantibodies.
AB  - T cell vaccination, the application of syngeneic attenuated T cells, has been
      shown to prevent effectively and treat experimental autoimmune diseases, but its
      mechanisms of action are poorly understood. Here we present data on the induction
      of a humoral anti-T cell response by T cell vaccination, capable of strongly
      inhibiting T cell proliferation and of ameliorating experimental autoimmune
      disease. T cell vaccination in the Lewis rat induced autoantibodies reactive with
      several syngeneic T cell proteins. These autoantibodies were not detectable in
      normal Lewis sera as assessed by immunoblotting and flow cytometry with intact
      syngeneic T cells. The autoantibody reactivity was not restricted to one
      idiotype, was detected as early as 1 week after vaccination and was dominated by
      IgG, suggesting the boosting of a naturally preformed humoral network by T cell
      vaccination. Recovery from passively or actively induced experimental autoimmune
      encephalomyelitis (EAE) in the Lewis rat, too, could be shown to be associated
      with the development of anti-T cell autoantibodies. In vitro, both the post-EAE
      and the post-vaccination sera had a strong suppressive effect on the
      proliferation of syngeneic T cell clones. This inhibition was shown to be
      mediated by antibodies and to be partly complement-dependent. In vivo, both kinds
      of sera were able to ameliorate EAE. This protective effect of the post
      vaccination sera was not idiotype-specific, since sera obtained after T cell
      vaccination with an unrelated T cell clone were similarly effective in
      suppressing EAE. These results suggest that anti-lymphocytic antibodies might
      play an immunoregulatory role that can be positively manipulated by T cell
      vaccination.

PMID- 9185876
TI  - Monokine-producing cells predominate in the recruitment phase of NOD insulitis
      while cells producing Th1-type cytokines characterize the effector phase.
AB  - Cells infiltrating the Langerhans' islets of prediabetic NOD females were
      isolated from 6 weeks to 6 months of age. These cells were assayed at a single
      cell level for production of eight different cytokines by intracellular
      immunofluorescent staining. Quiescent in vivo preactivated cells were detected by
      in vitro stimulation with PMA and ionomycin for 4 h. The cell recruitment phase,
      between 6 and 12 weeks of age, is predominated by production of the monokines IL
      1alpha, IL-6, and TNF After stimulation IFN-gamma and occasional IL-10 and GM-CSF
      producing cells could also be observed. This cytokine pattern occurs
      simultaneously with increasing insulitis, and we suggest that these cytokines are
      important in attracting inflammatory cells to the islets and maintaining the
      inflammatory state. A high frequency of endocrine cells producing IL-6 during
      this period may denote a stress response caused by initial beta-cell destruction
      due to cytokines released by the inflammatory cells. During the effector phase,
      between 4 and 6 months, there is a characteristic Th1 cytokine profile with
      lymphocytes producing IL-2, IFN-gamma and TNF, supposedly TNF-beta. No IL-4
      production could be detected and IL-10 was very rarely found, indicating the
      absence of a Th2 response. Our findings show that the effector phase in NOD
      insulitis is a Th1 rather than a Th2-mediated event. We also demonstrate that
      cytokines that may cause initial tissue destruction are produced during the
      recruitment of inflammatory cells.

PMID- 9185877
TI  - Aberrant V(H) gene utilization in patients with established insulin dependent
      diabetes mellitus.
AB  - We have compared the B-lymphocyte repertoire in seven IDDM patients with 12
      healthy controls by examining the variable heavy (V(H)) gene expression. The V(H)
      gene representation in the pool of pokeweed mitogen (PWM) stimulated,
      immunocompetent B cells and in the pool of naturally activated plasma cells
      (actual repertoire) was analysed by RNA-RNA in situ hybridization. Differences
      between IDDM patients and normal controls in the relative expression of several
      V(H) gene families were observed. In IDDM patients, the V(H)3 was significantly
      underrepresented in the PWM stimulated repertoire. In the actual B cell
      repertoire the V(H)5 clones were underrepresented among diabetic patients.
      Moreover, the altered distribution of V(H) gene usage between the PWM stimulated
      repertoire and the actual repertoire observed in normal controls was found to be
      less pronounced in the IDDM patients. This observation suggests a defect in the V
      gene directed cellular selection occurring between resting, immunocompetent B
      cells and naturally activated plasma cells. The possible implication of the
      observed aberrations in the B cell selection process for the pathogenesis of
      autoimmunity is discussed.

PMID- 9185878
TI  - High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect
      a hyperimmune state that precedes the onset of insulin-dependent diabetes.
AB  - Pancreatic islet beta-cell destruction leading to insulin-dependent diabetes
      mellitus (IDDM) is an autoimmune T cell-mediated process. Peripheral blood T
      cells, which proliferate to islet antigens such as glutamic acid decarboxylase
      (GAD), (pro)insulin or tyrosine phosphatase IA-2, can be detected in at-risk,
      first degree relatives of people with IDDM. However, cross-sectional studies
      cannot define the relationship between T cell responses and progression to IDDM.
      Longitudinal studies were therefore undertaken on 50 at-risk, first degree
      relatives tested at least yearly for up to 4 years, during which time five
      developed IDDM. Peripheral blood T cell responses to a GAD67(aa208-404)
      glutathione-S-transferase (GST) fusion protein, GST, insulin and tetanus toxoid
      were measured, together with antibodies to islet cells, GAD, insulin and IA-2.
      High levels of antibodies to GAD or insulin were generally associated with low T
      cell responses to these antigens. Relatives who developed IDDM were characterized
      by high levels of antibodies to insulin and/or islet cells, and high T cell
      responses to GAD67-GST and tetanus, but not insulin, in the 24 months before
      clinical diagnosis. Cross-sectionally, T cell responses to GAD67(aa208-404)-GST
      and to full-length GAD65-GST were highly correlated (r=0.75, P<0.002). In
      conclusion, increased cellular immunity to the mid region of GAD67 was a marker
      of late pre-clinical IDDM, but appears to reflect a more general, transient state
      of cellular immune hyperresponsiveness.

PMID- 9185879
TI  - Relationship between ANCA and clinical activity in inflammatory bowel disease:
      variation in prevalence of ANCA and evidence of heterogeneity.
AB  - Antineutrophil cytoplasmic antibodes (ANCA) are markers of necrotizing
      vasculitis. ANCA have been recently detected in the two forms of inflammatory
      bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). To assess
      the possible role of ANCA in the diagnosis and management of IBD we studied the
      prevalence of ANCA at diagnosis and during follow-up in a group of 89 IBD
      patients. The relationship between ANCA and clinical features of IBD was
      investigated. ANCA assayed by indirect immunofluorescence were detected in 38/52
      (73%) of the UC patients but only 6/37 (16.6%) of the CD patients (P<0.005) and
      in none of the controls. In the UC group, but not in the CD group, there was a
      positive correlation between ANCA and disease activity. The sensitivity and
      specificity of ANCA for the diagnosis of UC were 73 and 83.7% respectively. The
      most commonly observed pattern of ANCA in IBD patients was perinuclear: in 84% of
      the UC and 66.6% of the CD patients positive for ANCA, respectively. However,
      careful comparison of IFL patterns revealed some distinct features of IBD
      associated ANCA when compared to vasculitis-associated ANCA. In addition, most
      ANCA positive sera from IBD patients were negative for antibodies to proteinase 3
      and myeloperoxidase by ELISA. These results suggest that the autoantigens
      recognized by ANCA are different in patients with IBD from those with necrotising
      vasculitis.

PMID- 9185880
TI  - Accessibility of epitopes on the 52-kD Ro/SSA protein (Ro52) and on the RoRNP
      associated Ro52 protein as determined by anti-peptide antibodies.
AB  - The Ro ribonucleoprotein particle (RoRNP) is the target of a variety of specific
      anti-protein autoantibodies produced by patients with systemic autoimmune
      diseases. RoRNPs, the function of which remains elusive, appear to be rather
      heterogeneous in terms of their molecular composition. Among several Ro proteins,
      a protein of 52 kD (Ro52) has been identified, but its association with RoRNPs
      remains questionable. In this study, we first mapped the Ro52 regions that are
      accessible at the surface of the isolated protein, by means of antibodies raised
      in rabbits, against 39 overlapping synthetic peptides covering the whole Ro52
      molecule and using several different methods, including various ELISA formats and
      Western blotting (based on the use of recombinant Ro52) and immunoprecipitation
      of in vitro translated Ro52. Then, the whole set of anti-peptide antibodies was
      used to attempt to immunoprecipitate RoRNPs from a cell extract of K562 cells.
      RoRNPs, especially Ro(hY3)RNPs, were effectively immunoprecipitated by certain
      anti-peptide antibodies, indicating that Ro52 protein is associated with at least
      a subset of RoRNP particles. As expected, a number of epitopes available on the
      isolated Ro52 molecule are no longer accessible when Ro52 is associated with the
      RoRNP. Conversely, neotopes, among them at least one corresponding to a
      previously characterized epitope recognized by patients' antibodies, are only
      present at the surface of the particle and not detectable on the isolated Ro52
      protein.

PMID- 9185881
TI  - Characteristic generated alterations of autoantibody patterns in idiopathic
      thrombocytopenic purpura.
AB  - Using a Western blot technique that allows quantitative detection of antibody
      reactivities to a large number of antigens, serum IgG and IgM antibody
      repertoires were compared in a group of 19 patients with a diagnosis of
      idiopathic thrombocytopenic purpura (ITP) and respective healthy controls. The
      results show that, irrespective of the duration of thrombocytopenia, age of the
      patients, and type of therapy, all ITP donors share characteristic alterations of
      serum antibody reactivity patterns on homologous erythrocyte and liver antigens.
      Multiparametric analyses of the immunoreactivity data readily segregated the
      groups of ITP and healthy donors. Similar analyses also distinguished ITP sera
      from those of a group of patients with systemic lupus erythematosus (SLE). We
      conclude that ITP is an autoimmune disease associated with generalized
      alterations of antibody repertoires, that may be characteristic enough to allow
      for diagnosis.

PMID- 9185883
TI  - Lack of T cell response to cardiac myosin and a reduced response to PPD in
      patients with idiopathic dilated cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (IDCM) is the main cause of cardiac
      transplantation in young adults in the 20-40 years age group in the Western
      world. Recent evidence supports a possible role for autoimmune pathogenesis in
      IDCM and it has been suggested that T cells could mediate the disease. Cardiac
      myosin is one of the putative autoantigens recognized by antibodies from patients
      with IDCM, but T cell responses to cardiac myosin have not previously been
      assessed. Proliferation to cardiac myosin by peripheral blood mononuclear cells
      (PBMC) from patients, their relatives and controls was assessed in a
      lymphoproliferation assay specifically designed to measure low frequency T cell
      precursor responses. The study group consisted of 23 patients with IDCM and 29
      relatives. The control groups consisted of 10 patients with heart failure
      secondary to ischaemic heart disease (IHD) and 22 healthy laboratory controls. A
      response to myosin was observed in 16.7% of the subjects studied. However, these
      responses were all of low precursor frequency and no dose response for antigen
      specific proliferation could be observed. More importantly, there was no
      correlation between myosin-specific T cell responses and IDCM, as only one IDCM
      patient and four IDCM relatives (three out of the four with left ventricular
      enlargement (LVE)) were among the 14 subjects whose PBMC exhibited a
      proliferative response. However, proliferation of PBMC to purified protein
      derivative of Mycobacterium bovis (PPD) was significantly suppressed in IDCM
      patients when compared with the laboratory control group (P<0.05). PPD response
      data suggested that the PPD suppression correlated with disease progression. The
      results of our present study indicate an absence, or lack, of cardiac myosin
      specific peripheral blood T cells in IDCM patients, along with the possibility of
      underlying impaired cell mediated immunity, reflected in the suppressed responses
      to PPD. Future studies looking at T cell immune mechanisms in IDCM should
      concentrate on the analysis of T cells from the heart itself, or look at other
      potential cardiac antigens from normal and diseased heart tissue.

PMID- 9185882
TI  - TCR V beta usage by acetylcholine receptor-specific CD4+ T cells in myasthenia
      gravis.
AB  - In myasthenia gravis the muscle acetylcholine receptor (AChR) is the target of an
      autoimmune response. AChR epitopes recognized by CD4+ T cells in myasthenic
      patients have been identified. AChR-specific CD4+ cell lines can be propagated by
      stimulation of blood lymphocytes with synthetic or biosynthetic AChR sequences.
      We analysed, using a semi-quantitative PCR assay, the T cell receptor (TCR) V
      beta usage of 16 anti-AChR polyclonal CD4+ T cell lines of known epitope
      specificity, propagated from myasthenic patients using pools of overlapping
      peptides corresponding to the sequence of an AChR subunit, or individual
      synthetic AChR sequences. Twelve lines had been propagated for less than 2
      months, four lines for 3.5-5 months. Most lines had limited V beta usage, but in
      most cases different V beta regions were used for different epitopes in the same
      patient, and for the same epitope in different patients. In a few patients, the
      same V beta regions were used for recognition of different epitopes. The V beta 4
      and V beta 6 regions were used most frequently. These findings suggest that the
      potentially autoimmune T cells that survive clonal deletion have a limited TCR
      repertoire. Although the present data do allow conclusions on the role of a
      superantigen in triggering the anti-AChR autoimmune response, the finding that
      different V beta regions were used in different patients does not support an
      important role of a superantigen in the maintenance of the CD4+ response in
      myasthenia gravis.

PMID- 9185884
TI  - Science advice and the regulation of chemicals.

PMID- 9185885
TI  - A new shade of green.

PMID- 9185886
TI  - The predictive value of animal data in human cancer risk assessment.
AB  - Carcinogenic effects of chemicals can be investigated in animal experiments and
      epidemiological studies of exposed humans, mostly in the workplace. In this
      article epidemiologic evidence is compared with the animal data for 35 chemicals.
      Risk calculations are compared for 22 chemicals. The chemicals showing no or
      unclear carcinogenic effects in humans were more likely to show toxic side
      effects in the animal studies, indicating that the test concentrations were above
      the maximum tolerated dose. In addition, the animal experiments with these
      chemicals more often showed neoplastic effects on multiple sites than chemicals
      for which clear positive epidemiological studies are available. These findings
      may explain the existence of discrepancies between the outcomes of animal testing
      and human studies. They suggest that carcinogenic effects in multiple organs in
      animals could be seen as ultimate manifestations of the side effects of the
      testing method and that they have limited predictive value for the human
      situation.

PMID- 9185887
TI  - Quantitative risk assessment for a glass fiber insulation product.
AB  - California Proposition 65 (Prop65) provides a mechanism by which the manufacturer
      may perform a quantitative risk assessment to be used in determining the need for
      cancer warning labels. This paper presents a risk assessment under this
      regulation for professional and do-it-yourself insulation installers. It
      determines the level of insulation glass fiber exposure (specifically Owens
      Corning's R-25 PinkPlus with Miraflex) that, assuming a working lifetime
      exposure, poses no significant cancer risk under Prop65's regulations. "No
      significant risk" is defined under Prop65 as a lifetime risk of no more than one
      additional cancer case per 100,000 exposed persons, and nonsignificant exposure
      is defined as a working lifetime exposure associated with "no significant risk."
      This determination can be carried out despite the fact that the relevant
      underlying studies (i.e., chronic inhalation bioassays) of comparable glass wool
      fibers do not show tumorigenic activity. Nonsignificant exposures are estimated
      from (1) the most recent RCC chronic inhalation bioassay of nondurable fiberglass
      in rats; (2) intraperitoneal fiberglass injection studies in rats; (3) a
      distributional, decision analysis approach applied to four chronic inhalation rat
      bioassays of conventional fiberglass; (4) an extrapolation from the RCC chronic
      rat inhalation bioassay of durable refractory ceramic fibers; and (5) an
      extrapolation from the IOM chronic rat inhalation bioassay of durable E glass
      microfibers. When the EPA linear nonthreshold model is used, central estimates of
      nonsignificant exposure range from 0.36 fibers/cc (for the RCC chronic inhalation
      bioassay of fiberglass) through 21 fibers/cc (for the i.p. fiberglass injection
      studies). Lower 95% confidence bounds on these estimates vary from 0.17 fibers/cc
      through 13 fibers/cc. Estimates derived from the distributional approach or from
      applying the EPA linear nonthreshold model to chronic bioassays of durable fibers
      such as refractory ceramic fiber or E glass microfibers are intermediate to the
      other approaches. Estimates based on the Weibull 1.5-hit nonthreshold and 2-hit
      threshold models exceed by at least a factor of 10 the corresponding EPA linear
      nonthreshold estimates. The lowest nonsignificant exposures derived in this
      assessment are at least a factor of two higher than field exposures measured for
      professionals installing the R-25 fiberglass insulation product and are orders of
      magnitude higher than the estimated lifetime exposures for do-it-yourselfers.

PMID- 9185888
TI  - Categorical regression of toxicity data: a case study using aldicarb.
AB  - Categorical regression is a mathematical tool that can be adapted to estimate
      potential health risk from chemical exposures. By regressing ordered categories
      of toxic severity or pathological staging on exposure dose, this method can
      estimate the likelihood of observing any of the categories of severity at any
      dose level. Depending on the nature of the available data, these estimates can
      take the form of incidence rates for any of the categories in an exposed
      population or the probability of a new study conducted at a specified dose level
      being classified as one of the categories. Categorical regression is illustrated
      using toxicity data on aldicarb. For aldicarb, the data fall into three different
      groups: human clinical studies, dietary exposures in experimental animals, and
      accidental human exposure by contaminated crops. The U.S. EPA has assessed this
      literature and developed a reference dose (RfD) of 0.001 mg/kg-day. The results
      of applying categorical regression to data from human clinical studies suggests a
      maximum likelihood risk estimate of adverse effects of 0.008% at a 10-fold higher
      dose than the RfD when blood cholinesterase inhibition is not considered as an
      adverse effect. When blood cholinesterase inhibition of 20% or more is considered
      as an adverse effect, a maximum likelihood risk estimate of adverse effects is
      0.1% at a dose 10-fold higher than the RfD.

PMID- 9185889
TI  - Carcinogenicity testing and the evaluation of regulatory requirements for
      pharmaceuticals.
AB  - The results of rat and mouse carcinogenicity studies for 282 human
      pharmaceuticals in the FDA database were analyzed and compared as part of an
      International Conference on Harmonization (ICH) evaluation of rodent
      carcinogenicity studies and their utility for carcinogenicity testing. A majority
      of the carcinogenicity studies in the FDA database were carried out in Sprague
      Dawley-derived rats and Swiss-Webster-derived CD-1 mice in contrast to Fisher 344
      rats and B6C3F1 mice employed in National Toxicology Program (NTP) studies.
      Despite the differences in rodent strains, the relative proportion of compounds
      with positive findings (44.3%) and the degree of overall concordance between rats
      and mice (74.1%) in the FDA database were similar to the NTP rodent
      carcinogenicity database. Carcinogenicity studies in two rodent species are
      necessary primarily to identify trans-species tumorigens, which are considered to
      pose a relatively greater potential risk to humans than single species positive
      compounds. Two-year carcinogenicity studies in both rats and mice may not be the
      only means of identifying trans-species tumorigens. Sufficient experience is now
      available for some alternative in vivo carcinogenicity models to support their
      application as complementary studies in combination with a single 2-year
      carcinogenicity study to identify trans-species tumorigens. Our analysis of the
      rodent carcinogenicity studies supports such an approach for assessing
      carcinogenic potential without compromising the public health.

PMID- 9185890
TI  - Characterization of risks associated with the use of molinate.
AB  - A review of the toxicological information indicated that the most
      critical/sensitive toxicological endpoints of concern for human exposure to
      molinate, a thiocarbamate, preemergent herbicide, were adverse reproductive
      effects, neurotoxicity, and possible oncogenicity. Occupational and
      nonoccupational exposures to molinate potentially involved oral, dermal, and
      inhalation routes. Margins of safety for potential short-term, seasonal, annual,
      and lifetime exposures to workers associated with handling and application of
      molinate, the general public, and farmers were greater than the values
      conventionally recommended to protect people from the toxic effects of a
      chemical.

PMID- 9185891
TI  - Environmental risk harmonization: federal/state approaches to risk assessment and
      management.
AB  - As environmental laws and regulations have evolved in recent years, disparities
      have arisen in the assessment and management of similar risks by different
      governmental units. Such inconsistencies have had several adverse impacts. One is
      that resources may not be used most effectively to reduce risks and a second is
      that public confidence in government may be eroded and thus support for
      environmental protection. This article presents a summary of a conference and
      workshop that was held to address the sources of these disharmonies in risk
      assessment and risk management and to make recommendations as to how to improve
      the situation. It includes international, national, and state perspectives and
      utilizes a case study to illustrate the variety of issues associated with
      harmonizing risk assessment and risk management among governmental units. The
      workshop summaries demonstrate that, while there are presently many areas of
      disagreement, there are also significant issues upon which agreement can be
      reached and which can serve as the basis for further harmonization efforts.

PMID- 9185892
TI  - Effects of subchronic exposure of monochloramine in drinking water on male rats.
AB  - A subchronic rat study with paired-water control was conducted to resolve the
      question of whether monochloramine at 200 ppm in drinking water can cause reduced
      body weight gain and other changes observed in earlier investigations. Male
      Sprague-Dawley rats (93 +/- 5 g) were divided into three groups of 10 rats each:
      the treatment group was fed drinking water containing 200 ppm monochloramine, the
      control group was fed bicarbonate-buffered water ad libitum, and the paired-water
      control rats were given a daily volume of bicarbonate-buffered water equal to
      that consumed by the monochloramine treatment group. Compared to the control
      group, rats in the treatment group consumed an average of 42% less fluid and 16%
      less food over the 13-week treatment period and had 15-20% lower final body
      weight gain. Similar degrees of reduction in food consumption and body weight
      gain were observed in the paired-water rats. A decreased liver to body weight
      ratio occurred in the treatment and paired-water groups. Increased inorganic
      phosphate, albumin, total protein, and urea nitrogen were detected in sera from
      both the treatment group and the paired-water groups. The paired-water animals
      had lower levels of white blood cells and lymphocytes, while the paired-water and
      monochloramine-treated groups had reduced monocyte counts. Except for a slightly
      increased response to Con A observed in splenic lymphocytes of the monochloramine
      treated rats (versus the paired-water), no significant changes were found in
      mitogen responsiveness to T cell, B cell, and B plus T cell mitogens or in
      splenic natural killer (NK) cell activities. There were no significant changes in
      serum levels of IgG, IgA, and IgM. The following biochemical parameters showed no
      significant variations among the three groups: serum thyroxin, liver phase I
      (PROD, EROD, and MROD) and phase II (UDPGT and GST) drug-metabolizing enzyme
      activities; serum and liver thiobarbituric acid-reactive substances (TBARS);
      bronchoalveolar lavage fluid protein and N-acetylgluosaminidase (NAGA) activity;
      and urinary ascorbic acid, protein, and NAGA activity. Histopathological
      examination revealed minimal to mild adaptive changes in the liver of the paired
      water and monochloramine-treated rats and in the thyroid of the monochloramine
      treated animals. No treatment-related cytological changes were found in red cells
      and bone marrow. The results indicate that the reduced body weight gain and the
      minor biochemical, hematological, immunological, and histopathological changes
      associated with subchronic exposure to 200 ppm monochloramine in drinking water
      (equivalent to an intake of 21.6 mg/kg/day) were largely related to the reduced
      water intake and food consumption and not caused by monochloramine.

PMID- 9185893
TI  - The rodent uterotrophic assay: critical protocol features, studies with nonyl
      phenols, and comparison with a yeast estrogenicity assay.
AB  - The major protocol features of the immature rat uterotrophic assay have been
      evaluated using a range of reference chemicals. The protocol variables considered
      include the selection of the test species and route of chemical administration,
      the age of the test animals, the maintenance diet used, and the specificity of
      the assay for estrogens. It is concluded that three daily oral administrations of
      test chemicals to 21- to 22-day-old rats, followed by determination of absolute
      uterus weights on the fourth day, provide a sensitive and toxicologically
      relevant in vivo estrogenicity assay. Rats are favored over mice for reasons of
      toxicological practice, but the choice of test species is probably not a critical
      protocol variable, as evidenced by the similar sensitivity of rats and mice to
      the uterotrophic activity of methoxychlor. Vaginal opening is shown to be a
      useful, but nondefinitive, adjunct to the uterotrophic assay. The ability of test
      chemicals to reduce or abolish the uterotrophic response of estradiol is
      suggested to provide a useful extension of the uterotrophic assay for the purpose
      of detecting antiestrogens. The results of a series of studies on the
      environmental estrogen nonyl phenol (NP), and its linear isomer n-nonyl phenol,
      confirm that branching of the aliphatic side chain is important for activity.
      17beta-Desoxyestradiol is shown to be of similar activity to estradiol in the
      uterotrophic assay and is suggested to represent the "parent" estrogen of NP.
      Benzoylation of NP and 17-desoxyestradiol did not affect their uterotrophic
      activity, in contrast to the enhancing effect of benzoylation on estradiol.
      Selected chemicals shown to be active in the immature rat uterotrophic assay were
      also evaluated in an in vitro yeast human estrogen receptor transactivation
      assay. Most of the chemicals gave similar qualitative responses to those seen in
      the uterotrophic assay, and the detection of the estrogen methoxychlor by the
      yeast assay evidenced a degree of intrinsic metabolic competence. However, the
      assay had a reduced ability (compared to rodents) to hydrolyze the benzoate ester
      of estradiol, and the estrogenic benzoate derivative of NP was not active in the
      yeast assay. These last results indicate that current metabolic deficiencies of
      in vitro estrogenicity assays will limit the value of negative data for the
      immediate future. The results described illustrate the intrinsic complexity of
      evaluating chemicals for estrogenic activities and confirm the need for rigorous
      attention to experimental design and criteria for assessing estrogenic activity.

PMID- 9185894
TI  - Considerations for toxicology studies of respiratory drug products.
AB  - The standard approaches for the preclinical development of chronically
      administered drugs also apply to most respiratory drugs. Modifications from the
      standard preclinical development plan, however, may be necessary if the drug is
      administered intranasally or by inhalation. Administration by these routes may
      result in airway toxicity and the intended patient population is often
      particularly susceptible. Current and former representatives of the Division of
      Pulmonary Drug Products (CDER, U.S. FDA) present this article to describe general
      principles of preclinical development for respiratory drug indications. The
      article addresses drugs intended for administration by the intranasal or
      inhalation routes. The article describes the types of studies recommended,
      considers the initial human dose, and discusses dose-escalation strategies in
      clinical trials. Other areas of special concern with intranasal or inhalation
      administration include immunotoxicity, reproductive toxicity, types of dosing
      apparatus, excipients and extractables, and formulation changes. The approaches
      described in this article are intended as general information and should be
      adapted to the scientific considerations and circumstances of a particular drug
      under development.

PMID- 9185895
TI  - "Inconsistency between workplace and spousal studies of environmental tobacco
      smoke and lung cancer".

PMID- 9185896
TI  - Gallop poll rates honesty and ethical standards.

PMID- 9185897
TI  - Neonatal care of very-low-birthweight infants in special-care units and neonatal
      intensive-care units in Stockholm. Early nasal continuous positive airway
      pressure versus mechanical ventilation: gains and losses.
AB  - Very-low-birthweight (VLBW) infants are usually intubated at birth and
      mechanically ventilated at neonatal intensive-care units (NICUs). The objectives
      of this study were to evaluate the use of early nasal continuous positive airway
      pressure (NCPAP) in a regional cohort and to determine to what extent VLBW
      infants need transfer to a regional NICU from special-care units (SCUs) that
      primarily use early NCPAP for respiratory care. We compared the outcome for
      infants at SCUs and NICUs in Stockholm County, Sweden, from 1988 to 1993. All
      infants with birthweights of less than 1501 g were included in this study (n =
      687). Fifty-nine per cent of the infants (400/687) were supported using only
      supplemental oxygen or NCPAP. Of these, 170 (25%) received only supplemental
      oxygen and 230 (34%) were supported only by NCPAP. A total of 350 (51%) infants
      received early NCPAP. Of these infants, 120 (34%) later required mechanical
      ventilation. Only 167 (24%) infants received mechanical ventilation from the
      beginning Failure of NCPAP was significantly associated with the presence of
      respiratory distress syndrome. A total of 161/412 (39%) infants were transferred
      from SCUs to NICUs. Of infants < or = 26 weeks' gestation and infants > 26 weeks,
      71% and 34% were transferred, respectively. Total mortality was 16%. The
      mortality for transfers was 20% compared to an overall mortality in SCU and NICU
      infants of 9% and 15%, respectively. The overall incidence of intraventricular
      haemorrhage (IVH), grade III-IV was 8%, periventricular leucomalacia (PVL) grade
      I-IV was 7%, retinopathy of prematurity (ROP) requiring cryotherapy was 4.3% and
      chronic lung disease (CLD) was 14%. There were significant differences in the
      incidence IVH, PVL, CLD and ROP between SCU and NICU infants in matched
      gestational age groups. In conclusion, infants with a gestational age of 27 weeks
      or more may often be adequately cared for at SCUs without mechanical ventilation
      by using early NCPAP. However, infants with a gestational age of 26 weeks or less
      should be transferred to tertiary-care centres preferably before birth, because
      they will often require mechanical ventilation.

PMID- 9185898
TI  - The Stockholm Neonatal Project: neonatal mortality and morbidity at the
      Children's Centre, Karolinska Hospital.
AB  - Two hundred and ninety-one very-low-birth-weight (VLBW) infants were studied
      prospectively during the period of 1988-1993. All inborn VLBW infants and most of
      the VLBW infants born in Greater Stockholm and requiring neonatal intensive care
      were included in this study. The overall mortality was 17.5% and the mortality in
      the group with the lowest gestational age at birth, i.e. 23-24 weeks, was 25%.
      The mortality for boys was higher than for the girls. The mode of delivery, i.e.
      vaginal versus caesarean section and multiple birth, did not seem to affect the
      mortality rate. Respiratory insufficiency and/or cerebral complications were the
      most common cause of neonatal death. Patent ductus arteriosus was found in 35% of
      the infants, of whom 43% needed surgical ligation. One-third of infants with
      retinopathy of prematurity (30/92) required cryotherapy.

PMID- 9185900
TI  - Perinatal risk factors and neuromotor behaviour during the neonatal period.
AB  - Preterm birth is associated with an increased risk for neurological handicaps.
      The purpose of the present study has been: to investigate the influence of
      perinatal risk factors on early neuromotor development during the neonatal
      period; to specify the neuromotor parameters particularly sensitive to perinatal
      complications; and to analyse whether the infant's age at test influences the
      results. Beside examination of passive/active muscle tone and automatic movements
      (22 parameters) was performed at 36 (101 infants) and 40 (153 infants)
      gestational weeks. Low birthweight and long treatment on a ventilator had a
      negative influence on the neuromotor behaviour at 36 weeks' gestation and white
      matter disturbances strongly affected the neuromotor parameters at 40 weeks. The
      development of rooting, sucking, swallowing and arm recoil after long-lasting
      ventilator treatment was affected by several neonatal risk factors. The
      development of passive muscle tone and several parameters measuring active muscle
      tone demonstrated individual consistency between tests, i.e. an infant's rank at
      36 weeks' gestation was unchanged 4 weeks later, and some other parameters were
      not as consistent. The present study shows that several perinatal risk factors
      influence neuromotor behaviour already during the neonatal period. In addition,
      the present study provides data on the neuromotor behaviour during the neonatal
      period that will be related to later neurodevelopmental examinations in order to
      evaluate the prognostic value of testing neuromotor development.

PMID- 9185899
TI  - Diagnosis of intracranial lesions in very-low-birthweight infants by ultrasound:
      incidence and association with potential risk factors.
AB  - This study was designed to determine the frequencies of germinal matrix and
      ventricular haemorrhages as well as lesions in the white matter diagnosed by
      ultrasonography. In subsequent studies the effects of perinatal brain lesions on
      the cognitive and motor development of preterm children will be presented.
      Lesions of the white matter are probably more damaging than intraventricular and
      subependymal bleeds. Therefore, a modified classification of the lesions was
      used, clearly separating bleeds from white matter pathology. The study includes
      291 infants with a body weight of < or = 1500 g consecutively admitted to the
      neonatal intensive-case unit at Karolinska Hospital from 1988 to 1993. Fifty-four
      (18.9%) died before 6 months. Two hundred and sixty-three infants were examined
      using ultrasound. Pathology due to bleeding was classified into three grades (B1
      3) similar to Papile's first three grades. Pathology in periventricular white
      matter was classified into four groups (W1-4): W1 = subtle and We = distinctive
      white matter echodensities; W3 = cyst formation; W4 = large, intense echodensity.
      Forty-nine patients had abnormalities in the periventricular white matter (15 W1,
      12 W2, 11 W3 and 11 W4) and 58 had subependymal (B1 = 29) or ventricular bleeding
      without (B2 = 13) or with dilatation (B3 = 16). Ventilator treatment was
      significantly associated with both B and W lesions. Low gestational age, low
      birthweight, small for gestational age, pre-eclampsia and caesarean section were
      significantly associated with B lesions whereas asphyxia, surfactant treatment,
      male patient sex and outborn were associate with W lesions; b 1-3 and W 1-4
      lesions were thus partly associated with different potential risk factors. The
      pre- and perinatal potential risk factors could only partly explain the variance
      in the frequency of B and W lesions, indicating that there are yet unidentified
      risk factors for intracranial ultrasonographic pathology.

PMID- 9185901
TI  - Psychomotor development at 10 months as related to neonatal health status: the
      Stockholm Neonatal Project.
AB  - The psychomotor development of 171 preterm very-low-birthweight (VLBW) infants
      (birthweight < or = 1500 g) at 10 months of corrected age was assessed by the
      Griffiths' Mental Developmental Scale. The developmental score was related to the
      prenatal and obstetric risk factors and to the neonatal health status of each
      infant. These results, in turn, were compared to findings for a reference group
      of full-term infants. This analysis revealed that prolonged ventilator treatment,
      patent ductus arteriosus, bronchopulmonary dysplasia, brain haemorrhage with
      ventricle dilatation, white matter lesions, low birthweight and low gestational
      age influenced psychomotor development in an unfavourable manner. Multiple
      regression analysis confirmed most of these correlations. Preterm birth per se
      (when children with risk factors were excluded) in general had no significant
      effect on psychomotor development. However, the early development of preterm
      infants with several neonatal risk factors was adversely affected.

PMID- 9185902
TI  - Nutrition and growth during infancy. The Copenhagen Cohort Study.

PMID- 9185903
TI  - That "admitting- you're wrong stuff".

PMID- 9185905
TI  - Erythema elevatum diutinum: a clinicopathological study of eight cases.
AB  - Erythema elevatum diutinum (EED) is a rare cutaneous condition that initially
      presents as leukocytoclastic vasculitis (LCCV) of the skin and later resolves
      with fibrosis. In addition to the LCCV, EED may show features reminiscent of
      other entities. For example, it may mimic lesions of dermatofibroma, granuloma
      annulare, granuloma faciale, or dermatitis herpetiformis. For this study, we
      reviewed the clinical records and 13 skin biopsies in eight patients with EED.
      One of the patients had concurrent pityriasis rubra pilaris, and another
      developed lesions of EED following and at the sites of mosquito bites; these
      associations have not been noted previously. In addition to such typical
      histopathological features as diffuse dermal involvement by neutrophils,
      eosinophils, and leukocytoclastic vasculitis, we also found two unusual patterns.
      The first was characterized by palisaded necrotizing granulomas, as previously
      described and associated with Churg-Strauss granuloma; the second condition
      simulated a pyogenicgranuloma--like lesion.

PMID- 9185904
TI  - Mixed connective tissue disease. A clinical, histologic, and immunofluorescence
      study of eight cases.
AB  - A study of the cutaneous eruptions of eight patients with mixed connective tissue
      disease (MCTD) was performed to better characterize its dermatopathology and to
      explore a role for the membrane attack complex of complement C5b-9 in lesional
      pathogenesis. Nine lesional skin biopsies were obtained from eight patients with
      MCTD and analyzed by conventional light microscopy. Direct immunofluorescence
      (IF) and indirect IF using a monoclonal antibody to C5b-9 were applied in six and
      five cases respectively. The biopsied cutaneous eruptions were characterized
      clinically as photo-distributed erythematosus annular and/or papulosquamous
      lesions mimnicking subacute cutaneous lupus erythematosus (SCLE) in five of eight
      patients as an ill-defined, telangiectatic, scaly patch on the face in one
      patient, palpable purpura in one patient, and dorsal hand blisters resembling
      porphyria cutanea tarda (PCT) in another. With the exception of the latter two
      patients, the histology appeared similar, comprising a cell poor and/or lichenoid
      interface dermatitis with suprabasilar exocytosis around necrotic keratinocytes
      in the absence of deep periadnexal or perivascular extension or conspicuous
      follicular plugging, a pattern similar to that of SCLE. However, the lesions
      differed from SCLE by virtue of vasculopathic alterations comprising vascular
      ectasia, hypovascularity, and/or luminal thrombosis confined to the superficial
      vascular plexus and a sclerodermoid tissue reaction, the latter seen in two
      cases. One biopsy showed a pustular leukocytoclastic vasculitis (LCV). In another
      case, a biopsied hand blister demonstrated a PCT-like appearance histologically,
      namely, pauci-inflammatory subepithelial blister formation with hyalinization of
      dermal papillae capillaries accompanied by an LCV. There was nuclear keratinocyte
      decoration with IgG and C5b-9 in all cases studied, accompanied by a positive
      lupus band test in two cases and homogenous deposition of immunoreactants along
      the dermoepidermal junction and within vessels in the PCT-like eruption. Granular
      vascular decoration with immunoreactants including C5b-9 was seen in two LCV
      cases and in two biopsies from rashes clinically mimicking SCLE. Although the
      epidermal pathology of MCTD mimicks that of SCLE, a concomitant vasculopathy
      paralleling that seen in skin lesions of dermatomyositis distinquishes the
      dermatopathology of MCTD from that of SCLE. Corroborating the role of
      microangiopathy in the pathogenesis of the skin lesions of MCTD was the
      demonstration of C5b-9 in blood vessels. The deposition of C5b-9 in keratinocytes
      may explain the pattern Of IgG decoration of keratinocytes; the formation of
      plasmalemmal pores may permit binding of immunoglobulin to antigens in the
      nucleus and/or cytosol. The C 5b-9 complex may be the effector mechanism of
      epithelial and/or endothelial cell injury in MCTD or may serve to augment the
      effects of antibody-dependent cellular cytotoxicity.

PMID- 9185907
TI  - Apoptosis in atypical fibroxanthoma and pleomorphic malignant fibrous
      histiocytoma.
AB  - Explanations for the disparate behavior of atypical fibroxanthoma (AFX) as
      compared with pleomorphic malignant fibrous histiocytoma (MFH) have included the
      proposition that the former is a pseudosarcoma. Nonetheless, these tumors are now
      widely regarded as the same process, but with AFX behaving benignly by virtue of
      its superficial location. However, a neoplasm's metastastatic potential has been
      proposed to be related to apoptosis. Therefore, the aim of the present study was
      to examine apoptotic counts, in conjunction with two important regulators of
      apoptosis: p53 and bcl-2, to determine if a distinction exists that may account
      for the different outcomes of these lesions. There was no significant statistical
      difference between eight AFX and nine pleomorphic MFH in terms of apoptotic
      behavior, proliferative indexes, p53 protein expression, or presence of bcl-2
      product. Therefore, our results further support the contention that AFX should be
      regarded as a form of pleomorphic MFH, which demonstrates low malignant potential
      by virtue of its location in readily accessible sites.

PMID- 9185906
TI  - Angiomatoid malignant fibrous histiocytoma revisited. An immunohistochemical and
      DNA ploidy analysis.
AB  - A histologic, immunohistochemical, and DNA ploidy analyses were performed on two
      cases of angiomatoid malignant fibrous histiocytoma to ascertain the histogenesis
      and relationship of endothelial, histiocytic, and fibroblastic elements. Both
      cases were slowly growing, grossly encapsulated. Subcutaneous masses resected
      from pediatric patients. Microscopically, the tumors were composed of solid
      masses of epithelioid and spindle cells with abnormal endothelial-lined and blood
      filled cystic spaces surrounded by normal vascular structures and aggregates of
      lymphocytes occasionally forming germinal follicles. The tumor cells stained
      exclusively with CD34 and vimentin antibodies. Tumor-associated vessels stained
      for CD31, CD34, vimentin, and Ulex europaeus. Occasional cells within germinal
      follicles stained for lysozyme, CD68, and HAM56. Ploidy analysis of tumor cells
      showed intermediate aneuploidy with a DNA index of 1.14. Blood vessels within and
      surrounding the tumor as well as inflammatory cells were DNA euploid. These
      studies suggest that the tumor--though comprised of histologically and
      immunohistochemically benign-appearing euploid endothelial, fibroblastic, and
      inflammatory elements--contains an aneuploid population of undifferentiated
      mesenchymal cells.

PMID- 9185908
TI  - Epidermolytic acanthomas: clinical characteristics and immunohistochemical
      features.
AB  - Epidermolytic hyperkeratosis in bullous congenital ichthyosiform erythroderma
      results from mutations in the K1 and K10 genes. Epidermolytic acanthomas are
      solitary or multiple lesions with microscopic features that are identical to
      those in bullous congenital ichthyosiform erythroderma. In this study, the
      clinical and epidemiologic characteristics of epidermolytic acanthomas were
      summarized, and the expression of keratins (using antibodies to K1, K6, K10, K14,
      K16, and K19) in five solitary epidermolytic acanthomas was determined using
      immunohistochemistry techniques. The intensity of staining for K1 and K10 was (a)
      less in the altered granular layer, as compared to the adjacent nonaltered
      granular layer of the lesional skin, and (b) less in the lesional skin as
      compared to the perilesional, histologically normal-appearing skin. Expression of
      K6 and K16 was noted not only in the basal layer and suprabasal layers of the
      lesions, but also in the corresponding layers of the adjacent normal skin.
      Staining for K14 was also observed in the basal layers and suprabasal layers of
      the lesional and adjacent normal epidermis; within the lesional and perilesional
      normal skin, the intensity of positive staining for K14 was greater in the basal
      layers than in the suprabasal layers of the epidermis. The specimens did not
      stain for K19. In conclusion, using immunohistochemistry techniques on solitary
      epidermolytic acanthomas, we were able to demonstrate (1) an abnormality in K1
      and K10 expression in the lesional skin as compared to the adjacent,
      histologically normal-appearing skin and (b) the expression of hyperproliferative
      keratins not only with the lesional skin, but also in the perilesional normal
      skin. We hypothesize that the pathogenesis of epidermolytic hyperkeratosis in
      lesions of solitary epidermolytic acanthomas results from mutations in the K1 and
      K10 genes.

PMID- 9185909
TI  - Verocay body--prominent cutaneous schwannoma.
AB  - We report on eight cases of a distinct variant of cutaneous schwannoma
      characterized by prominent Verocay body formation (75-100% of the tumor bulk)
      that may cause considerable diagnostic difficulties. Like ordinary cutaneous
      schwannomas, these lesions preferred the head and neck region of young adults
      without sexual predilection and were clinically interpreted as cyst, basal cell
      carcinoma, or nevus. Histological examination revealed well-circumscribed
      nodules. Three of them consisted exclusively of nodular or ribbon-like Verocay
      bodies. A variable admixture of Antoni A or B type of differentiation (< 25%) was
      seen in five other cases. The following patterns were seen: fascicular spindle
      shaped, onion-like epithelioid, myxoid-hypocellular, and degenerated ("ancient")
      with prominent fibrosis/hyalinosis and occasional bizarre giant cells.
      Immunohistochemically, the lesions were positive for S-100 protein (and vimentin)
      but negative for a broad panel of neurogenic and intermediate filament markers.
      The capsule showed focal labeling for EMA and--when it was markedly thickened-
      also for SMA. Labeling with E9, an anti-metallothionein marker indicative of cell
      activity, was negative, underscoring the slow growth potential of these lesions.
      No recurrence was seen in the six patients with follow-up information. The
      differential diagnosis includes other lesions with prominent palisading.
      (Amianthoid) myofibroblastoma and palisading leiomyoma are consistently positive
      for SMA and desmin, respectively. Palisading cutaneous fibrous histiocytoma and
      myofibroblastic dermatofibroma are variably positive for Factor XIIIa, SMA, and
      E9 and/or NK1C3 (CD57). Palisaded encapsulated neuromas are primarilly
      differentiated by the presence of nerve fibers with myelin sheaths.

PMID- 9185910
TI  - Expression of keratins (K10 and K17) in steatocystoma multiplex, eruptive vellus
      hair cysts, and epidermoid and trichilemmal cysts.
AB  - We compared the patterns of keratin 10 (K10) and keratin 17 (K17) expression in
      epidermoid cysts, trichilemmal cysts, eruptive vellus hair cysts, and
      steatocystoma multiplex. Epidermoid cysts expressed K10 and eruptive vellus hair
      cysts expressed K17, whereas trichilemmal cysts and steatocystoma multiplex
      showed expression of both K10 and K17. Our findings support the opinion that
      eruptive vellus hair cysts, which stained negative for K10, and steatocystoma
      multiplex are distinct entities and not variants of one disorder.

PMID- 9185911
TI  - bcl-2 expression in pilomatricoma.
AB  - Pilomatricoma is a distinctive tumor characterized by a dual population of
      proliferating basophilic cells and diagnostic shadow cells, believed to arise
      from the hair matrix. The normal hair matrix undergoes defined cycles of growth
      (anagen), regression (catagen), and resting (telogen) that are regulated by
      programmed cell death (apoptosis). bcl-2 is a proto-oncogene that helps to
      suppress apoptosis in both benign and malignant tumors. In addition, both
      apoptosis and bel-2 are critical factors in normal hair follicle development. In
      order to clarify the role of bcl-1, we used immunohistochemical means to study 10
      cases of histologically proven pilomatricoma for bcl-2 expression. The study
      design included both positive and negative controls. All of the pilomatricomas in
      our series were strongly decorated by bcl-2 immunostaining. Based on our findings
      of increased bcl-2 staining, we concluded that the faulty suppression of
      apoptosis contributes to the pathogenesis of pilomatricoma.

PMID- 9185912
TI  - Cutaneous verruca with genital human papillomavirus in a 2-year-old girl.
AB  - Human papillomavirus (HPV) is the etiologic agent of warts and condyloma
      acuminatum (CDA). Condyloma acuminatium is believed to result from sexual
      transmission of HPV types 6 and 11 in adults. In contrast, nonsexual transmission
      of CDA occurs frequently between children and caregivers. Nonsexual-CDA are
      present almost exclusively in the mucosal epithelium in children. The authors
      analyzed a rapidly growing cutaneous wart on the thigh of a two-year-old girl for
      the presence of oncogenic and nononcogenic HPV types by in situ hybridization.
      This cutaneous wart was found to have the HPV types commonly found in CDA, namely
      types 6 and/or 11. This is an unusual finding and suggests that verruca vulgaris
      may result from papillomavirsuses other than HPV 2 in children.

PMID- 9185913
TI  - Malignant mesothelioma metastatic to the skin, presenting as inflammatory
      carcinoma.
AB  - We report a 50-year-old man with a history of malignant pleural mesothelioma
      diagnosed 1 year previously and treated with pneumonectomy and radiotherapy who
      presented with an erythematous eruption on the left chest wall. A skin biopsy
      showed a proliferation of malignant epithelioid cells lining irregular clefts in
      the dermis. Some groups of cells were observed filling vascular lumina.
      Immunohistochemically, the tumor cells expressed cytokeratins (with antibodies
      AE1/AE3, MNF 116, and CAM 5.2), and epithelial membrane antigen (EMA), and were
      negative with Ulex europaeus (UE) and for carcinoembryonic antigen (CEA), CD34,
      CD15 (with LeuM1 antibody), and factor VIII-related antigen (FVIIIra). The
      histologic features and immunohistochemical profile were comparable to those
      observed in the primary pleural mesothelioma. This is the first reported case in
      which malignant mesothelioma metastatic to the skin presented as "inflammatory
      carcinoma." Although a very uncommon presentation, mesothelioma should be
      considered in the differential diagnosis of erythematous eruptions on the chest.

PMID- 9185914
TI  - Localized myofibroblastic proliferation in the neck of a patient with an IgG
      myeloma.
AB  - We describe a myofibroblastic proliferation in the neck and lower part of the
      face involving skin and muscle of a 68-year-old female patient with an IgG kappa
      myeloma. Biopsies showed a fusocellular proliferation with scarce pseudoganglion
      cells involving the superficial fascia and the cutaneous muscle of the neck. The
      proliferative cells showed immunohistochemical and ultrastructural features
      characteristic of myofibrobasts with a proliferating cell nuclear antigen index
      of 48%; 42% of the cells displayed HLADR-positive membrane staining. Cellular
      proliferation subsided following the use of immunosuppressive drugs. Eight months
      after initial consultation, the patient developed polymyositis without a
      proliferative component and died of aplastic anemia.

PMID- 9185915
TI  - Benign polymorphous mesenchymal tumor (mesenchymal hamartoma) of soft parts.
      Report of two cases.
AB  - We report two cases of a previously unrecognized neoplasm, each characterized by
      prominent lobular configuration in the subcutaneous tissue. Within the neoplasms
      were distinctive garland-shaped structures composed of glial fibrillary acidic
      protein (GFAP) positive cells with indistinct borders, encased in concentric
      loops of fine collage fibers. In some areas, the neoplastic cells were
      distributed in small lacunae. The extracellular space between the collagenous
      tissue and the cells was filled with copious myxoid matrix. One of the neoplasms
      also demonstrated areas with spindle cells which resembled leiomyoma.
      Immunohistochemistry was negative for smooth muscle actin (1A4), muscle actin
      (HHF35), S-100 protein, desmin, cytokeratin, KP1, and epithelial membrane antigen
      (EMA.) Currently, both patients are free of recurrence or metastasis 2 and 4
      years after primary surgical excision. The neoplasms, which we term benign
      polymorphous mesenchymal tumor of soft parts (BPMT), should be distinguished from
      ossifying fibromyxoid tumor of soft parts, extraskeletal mesenchymal
      chondrosarcoma, neoplasms arising in ectopic breast tissue and mixed tumor of the
      skin.

PMID- 9185916
TI  - Indeterminate cell histiocytosis: a rare histiocytic disorder.
AB  - A 64-year-old woman, otherwise healthy, presented with multiple reddish-brown,
      slightly yellowish papules on the face and neck, which had developed 3 years
      earlier. The lesions were painless and nonpruritic and varied in diameter from 1
      to 5 mm. Histological and immunohistochemical examination of cutaneous biopsies
      revealed a diffuse dermal infiltrate composed mainly of histiocytes which
      expressed both Langerhans cell as well as monocytic/macrophages cell marker
      characteristics. Electron microscopic studies revealed no Birbeck granules within
      the cytoplasm of the neoplastic cells, leading to a diagnosis of indeterminate
      cell histiocytosis. Indeterminate cell histiocytosis is a very rare disease
      characterized by the proliferation of indeterminate histiocytes which
      morphologically and immunophenotypically resemble Langerhans cells but lack
      Birbeck granules.

PMID- 9185917
TI  - CD30-positive multilobated peripheral T-cell lymphoma primarily involving the
      subcutaneous tissue.
AB  - A 55-year-old woman presented with an inflammatory panniculitis-like plaque on
      her right thigh. Biopsy disclosed a subcutaneous infiltrate of multilobated T
      lymphocytes strongly expressing the CD30 antigen. A complete clinical remission
      was achieved with local radiation therapy, with no evidence of recurrence in 13
      months of follow-up. To our knowledge, our patient is the first reported case of
      CD30-positive multilobated peripheral T-cell lymphoma primarily involving the
      subcutaneous tissue.

PMID- 9185918
TI  - Case of malignant lymphoma associated with primary systemic plasmacytosis with
      polyclonal hypergammaglobulinemia.
AB  - Systemic plasmacytosis (SP), which has a histologic appearance similar to that of
      multicentric Castleman's disease (MCD), is also known as benign plasma cell
      proliferation with polyclonal hypergammaglobulinemia, cutaneous plasmacytosis,
      and/or generalized plasmacytic lymphadenopathy. The prognosis of SP reportedly
      has been good. A 59-year-old Japanese man was treated for multiple cutaneous
      lesions of his trunk as well as polyclonal hypergammaglobulinemia. A skin biopsy
      showed infiltration of lymphocytes and polyclonal plasma cells in the dermis. The
      patient developed enlarged superficial lymph nodes 5 years later, and T-cell
      lymphoma, diffuse mixed type, was diagnosed. At that time, his cutaneous
      plasmacytosis remained but the polyclonal hypergammaglobulinemia had resolved.
      Ours is the first reported case of SP to be complicated by the development of T
      cell lymphoma.

PMID- 9185919
TI  - Simultaneous occurrence of multiple trichoblastomas and steatocystoma multiplex.
AB  - We present a 55-year old man who, since age 21, progressively developed multiple
      papules and nodules on the face and upper trunk. Light microscopic examination of
      some of the neoplasms showed trichoblastomas, while others had histopathological
      features of trichoepithelioma and steatocystoma. Simultaneous occurrence of
      multiple trichoblastomas/trichoepitheliomas and steatocystomas, not reported
      previously, could represent multiple neoplasms involving differentiation toward
      different components of the folliculosebaceous unit.

PMID- 9185921
TI  - Malignant melanoma in situ colonizing basal cell carcinoma. A simulator of
      invasive melanoma.
AB  - Coexisting (collision) cutaneous neoplasms of various types and combinations are
      well documented but relatively uncommon. This report describes the unusual
      occurrence of a malignant melanoma in situ (MMIS) colonizing a basal cell
      carcinoma (BCC). A 69-year-old man was considered clinically to have a
      melanocytic neoplasm or a pigmented BCC of the right ear. Biopsy showed an MMIS,
      lentigo maligna type, juxtaposed to a typical BCC. The MMIS extended peripherally
      and into the BCC. Interspersed among the basaloid epithelial cell aggregates that
      extended 1.70 mm into the dermis were atypical melanocytes. Immunoperoxidase
      stains with high molecular weight cytokeratin (903) stained the basaloid
      keratinocytes but not the melanocytes. Conversely, HMB-45 and Mel-5 intensely
      stained the melanocytes throughout the BCC and in the epidermis but did not
      demonstrate any separate aggregates of invasive melanoma. These findings suggest
      that the position of the MMIS was a consequence of BCC colonization. Because the
      prognosis of malignant melanoma correlates most closely with the thickness of the
      lesion, this case poses a unique problem in predicting the biology of the lesion,
      which we believe should not be considered invasive melanoma.

PMID- 9185920
TI  - Malignant histiocytosis presenting as multiple erythematous plaques and cutaneous
      depigmentation.
AB  - We report on a patient with malignant histiocytosis (MH) presenting as multiple
      erythematous plaques and cutaneous depigmentation on her neck and chest. In a
      biopsy of an erythematous plaque, atypical large, foamy histiocytes infiltrated
      the dermis and positively stained with antibodies to lysozyme, leukocyte common
      antigen, and KP-1 (CD68). A few similar atypical cells were present in the
      superficial dermis focally in the depigmented areas. With use of
      immunohistochemical studies, most cases previously diagnosed as MH have been
      reclassified as T-cell lymphoma, B-cell lymphoma, or Ki-1-positive anaplastic
      large cell lymphoma. However, a few cases of "true" MH characterized by authentic
      histiocytes have been reported, presenting usually as red nodules. To our
      knowledge, our patient is the first with MH to present with erythematous plaques
      and vitiligo-like depigmentation.

PMID- 9185922
TI  - Nevus spilus (speckled lentiginous nevus) associated with a nodular neurotized
      nevus.
AB  - We report a case of nevus spilus with neurotized nevus studied by
      immunohistochemical methods using S-100, leu-6, glial fibrillary acid protein
      (GFAP), and myelin basic protein (MBP). Histologic findings of the speckled
      lesion showed irregular rete ridge elongation, increased epidermal melanocytes
      and melanin in the epidermis, and scattered nevus cell nests in the upper dermis,
      but showed neurotized nevus in the deep dermis, which has many features of
      neurofibroma. Diffuse expression of S-100 protein and MBP, focal staining with
      GFAP, and lack of staining with leu-7 were observed, Leu-7, positive only in
      neurofibromas and not in neurotized nevus, appears to be the more pertinent
      method for distinguishing neurotized nevus from neurofibroma.

PMID- 9185923
TI  - Case of dermatofibroma with monster cells: a review and an immunohistochemical
      study.
AB  - We report a dermatofibroma with monster cells. The patient was a 79-year-old
      woman who had a dark-brown nodule of her left leg for approximately 3 years. The
      lesion was composed of spindle-shaped fibroblastic cells, histiocytic cells, and
      multinucleated giant cells. Most of the histiocytic cells had foamy cytoplasm
      with numerous hemosiderin deposits. In addition to these cells, bizarre
      multinucleated cells with markedly hyperchromatic nuclei and xanthomatous cells
      with very large nuclei (monster cells) were also noted. No mitotic figures of the
      cellular components were present. This lesion has been shown to be completely
      benign despite the presence of pleomorphic or bizarre cells. From a clinical
      standpoint, recognition of a benign lesion of this type is very important since
      an incorrect histologic interpretation could result in inappropriate treatment.

PMID- 9185924
TI  - Suicide by self-incineration.
AB  - During a 10-year period (1980-1989), at least 43 cases of self-incineration with
      lethal outcome took place in Denmark. The incidence seems to be increasing: 11
      cases took place in the first 5 years and 32 cases in the last 5 years. An even
      sex ratio as found (male:female = 23:20). The median age was 43 years, with a
      broad age range (20-87). Many incidents of self-incineration as a form of
      political protest were reported in the press especially during the 1960s and
      1970s, and the press reports often inspired others to commit suicide in the same
      way. None of the cases in our investigation were politically motivated or
      reported in the press, and only one case could have been inspired by another
      similar case. Other investigations have shown that self-incineration is more
      common in some cultures than in others, and many have found that a religious
      motivation was common. In our investigation, all victims were of Danish origin,
      and a religious motive played no significant role. Most of the victims were
      suffering from mental illness, and a majority had tried to commit suicide before.
      None of the victims left a suicide note. The scene was most often at home and
      indoors--only a minority committed suicide in remote areas of the countryside.
      Most were found dead at the scene, and the cause of death was usually heat
      exposure. Only a minority had a lethal carboxy-hemoglobin (CO-Hb) concentration.
      It is concluded that close cooperation between police, fire experts, and the
      forensic pathologist is necessary to permit a correct classification of the mode
      of death in these cases.

PMID- 9185925
TI  - Lawsuits against medical examiners or coroners arising from death certificates.
AB  - A data base search through Westlaw was conducted to ascertain lawsuits in which a
      medical examiner or coroner (ME/C) was sued because of the cause or manner of
      death stated on the death certificate. Sixteen reported cases were found between
      1948 and 1995, with 10 of the cases occurring since 1985. The frequency of
      reported cases is approximately 1/400,000 ME/C death certificates, but based on
      certain assumptions, the actual frequency may be estimated at 1/40,000 ME/C death
      certificates. Nine cases involved plaintiffs who contested when the manner of
      death was indicated as suicide. In 15 of the 16 cases, the lower court decision
      favored the ME/C viewpoint. Five of the 15 decisions were ultimately reversed by
      a higher court, but the ultimate outcomes of these cases were not available.
      Overall, it appears that most courts and decisions have recognized ME/C actions
      as discretionary or immune and that ME/Cs have been at low risk for such suits to
      date. This seems especially true if the ME/C position is defensible and the ME/C
      has acted in accordance with statute and without evidence of corruption,
      incompetence, arbitrariness, capriciousness, abuse of discretion, or outrageous
      conduct.

PMID- 9185926
TI  - Pretrial communication with defense counsel by medical examiners' pathologists.
AB  - Forensic pathologists (FPs) form opinions in homicide trials and often are key
      witnesses for the prosecution. Early access to the FP by defense counsel may be
      strategically important, but state statutes differ regarding pretrial
      availability of the autopsy report to the defense, and the degree of pretrial
      communication that is permissible or desirable between the FP and defense is
      unclear. We surveyed a sample of FPs to determine their practices and opinions
      regarding pretrial communication with the defense. We compared responses with
      years of training, early professional role models, local autopsy report
      disclosure statutes, and reasons for practices. All respondents indicated a
      willingness to informally communicate with the defense, but many would notify the
      prosecutor and some wanted prosecutor's presence or permission. Prosecutorial
      involvement correlated with work load and with stated reasons for practices. Case
      law in most states prohibits the prosecutor from interfering with defense
      communication with witnesses, including experts. However, witnesses are free to
      refuse to talk informally to the defense. Some states limit publication of the
      autopsy report outside formal trial discovery procedures. Only one state,
      Arkansas, does not allow the medical examiner to give out any information,
      thereby precluding informal communication with the defense in that state.

PMID- 9185927
TI  - Traumatic tear of the basilar artery associated with vertebral column injuries.
AB  - An unusual case of traumatic basal subarachnoid hemorrhage (SAH) due to a
      mechanical tear of the basilar artery is reported. A 70-year-old man who had been
      suffering from cerebrovascular dementia was found dead in a ditch. Externally,
      subcutaneous hemorrhage with abrasions was observed on the left side of the
      forehead, face, and lower jaw, together with small contusions in the left
      superciliary arch. Internally, a 3-mm-long transversal tear of the basilar artery
      was observed, and dislocations of both C6-C7 and T1-T2 as well as a small
      fracture of the processus spinosus of C5 were found. No pathological vascular
      lesions such as aneurysms and vasculitis, other than arteriosclerosis, were
      observed in the vertebral-basilar system. Ethanol was not detected in the
      intracardiac blood or in the urine. These findings indicate that when the man
      fell into the ditch, severe hyperextension occurred as a result of minor blunt
      forces to the face, and that the traumatic tear of the basilar artery was
      mechanically caused by overstretching due to hyperextension of the head. It is
      also suggested that due to his advanced age the muscle tone of the neck might
      have declined, impairing its defense action, and that head hyperextension might,
      therefore, occur rather more readily under such conditions.

PMID- 9185928
TI  - Death due to a methane gas explosion in a tunnel on urban reclaimed land.
AB  - Studies of four male victims who were killed in an accidental tunnel gas
      explosion on urban reclaimed land are described. The studies were judicial
      autopsy examinations to determine the precise causes of death. Two men died of
      carbon monoxide intoxication, one died of massive brain damage, and the fourth
      died of drowning. The concentrations of methane in several organs were much lower
      than the lethal level, whereas those in adipose tissue were relatively high.
      These findings indicated that a low concentration of methane was almost always
      present in the atmosphere at the construction site. Recently, coal mine accidents
      have been decreasing in Japan. However, there is still a possibility of
      underground explosions or gas leaks in confined spaces other than coal mines. To
      determine the precise cause of death in such cases, careful autopsies and other
      examinations should be performed using methods similar to those used in coal mine
      accidents.

PMID- 9185929
TI  - Complications following butane inhalation and flash fire.
AB  - Solvent inhalation is a well-documented form of drug abuse that can cause
      euphoria and hallucinations. Sudden death involving a volatile substance is most
      commonly caused by cardiac arrythmias, asphyxia, direct drug effects, and trauma.
      The victim in this paper suffered superficial partial thickness (12% total body
      surface area) burns from a flash fire that occurred when lighting a match after
      inhaling butane in an enclosed vehicle. The victim was admitted to the hospital
      for 2 days of observation but did not develop any respiratory symptoms under 2
      days following her release. The victim died during her readmission, 9 days after
      the flash fire. Postmortem examination showed extensive epithelial injury from
      the upper airway and trachea to the terminal bronchioles, most likely due in part
      to both the initial inhalation injury and the resulting adult respiratory
      distress syndrome (ARDS) and staphylococcal infection. Many victims with
      superficial burn injuries may not seek medical attention owing to either
      embarrassment or fear of legal prosecution. Even those who do seek medical
      assistance may not reveal solvent abuse as the cause of their injuries. It is
      possible that delayed death may occur at home following volatile substance abuse
      but may remain unrecognized even with a thorough scene investigation.

PMID- 9185930
TI  - Fatal railway injuries in Cape Town, South Africa.
AB  - To describe the features of railway-related deaths in Cape Town, South Africa, we
      reviewed demographic, autopsy, and accident report data on all such deaths
      between 1 April 1992 and 30 September 1994. Of the 379 railway-related deaths, 27
      were among pedestrians or commuters who were hit by a train while crossing the
      track, 38 were among commuters who fell from moving trains, 32 were suicides, 43
      were the result of criminal violence on trains or at railway stations, and 38
      were due to other causes. Most railway fatalities were among men between the ages
      of 25 and 44 years. About half of all railway fatalities occurred at peak
      commuting times, with high levels of violence (often robbery related) recorded
      during the evening peak. A blood alcohol concentration > 0.1 g/100 ml was found
      in 35% of the people who died from crossing the track or falling from moving
      trains. Fatal railway injury is characterized by extensive disruption of more
      than one body region. The high levels of fatal railway injury make a strong case
      for a range of injury control interventions, including ticket control,
      surveillance, law enforcement, and safety engineering.

PMID- 9185931
TI  - Zinc toxicity following massive coin ingestion.
AB  - This is the first reported case of human fatality associated with zinc
      intoxication following a massive ingestion of coins. Four hundred and sixty-one
      coins were removed form the gastrointestinal tract of a schizophrenic patient
      during the course of hospitalization. Many of the post-1981 pennies, which
      consist primarily of zinc, showed severe corrosion due to their prolonged contact
      with acidic gastric juice. The patient presented with clinical manifestations
      consistent with the local corrosive as well as systemic effects of zinc
      intoxication and died 40 days after admission with multi-system organ failure.
      Tissue samples of the kidneys, pancreas, and liver obtained at autopsy revealed
      acute tubular necrosis, mild fibrosis, and acute massive necrosis, respectively,
      and contained high levels of zinc. The overall effects of zinc intoxication on
      the various organ systems, possible hematological derangement, and the impairment
      of copper absorption as well as the outcome with treatment are discussed.

PMID- 9185932
TI  - Forensic medicine in Israel.
AB  - We discuss the Israeli medicolegal system, which is rooted in remnants of British
      jurisprudence. Forensic services for the entire country and the occupied
      territories (Judea and Samaria), and now the Palestinian Autonomy (Gaza Strip and
      Jericho), are supplied by one central institute located in Tel Aviv. That
      organization, the L. Greenberg Institute of Forensic Medicine, is a department of
      the Ministry of Health and has academic affiliation with the University of Tel
      Aviv. About 2,000 necroscopic examinations are performed annually, and the types
      of cases encountered in the forensic practices in Israel are noted. The academic
      and research activities of the Institute's staff are described, with emphasis on
      collaboration with overseas forensic scientists. The modern history of the
      country is reflected in the chronicle of the evolution of its forensic medicine.

PMID- 9185933
TI  - Determination of postmortem interval by sampling vitreous humour.
AB  - Estimation of postmortem interval (PMI) by analyses of vitreous humor has certain
      advantages over analyses of blood and cerebrospinal fluid (CSF). Certain
      substances, including potassium and hypoxanthine (Hx), have been shown to exhibit
      postmortem increase in concentration in vitreous humor in a linear fashion. In
      the present study, potassium and Hx concentrations were measured in 100 subjects
      with known PMIs. Three previously published equations were used to estimate the
      PMI using these measurements, and the accuracy of the equations was assessed.
      Simple linear regression analyses were performed on the data collected, and new
      equations for estimation of PMI were constructed. Estimates made using these
      equations were of comparable or better accuracy than those made using the
      published equations. It was observed that using both potassium and Hx
      measurements to estimate the PMI were associated with increased accuracy in all
      circumstances.

PMID- 9185934
TI  - Evaluation of agonal artifacts in the myocardium using a combination of
      histological stains and immunohistochemistry.
AB  - The problem of discrimination between agonal artifacts and intravital ischemic
      myocardial lesions was studied with four histochemical stains [hematoxylin-eosin,
      Mallory's phosphotungstic acid hematoxylin (PTAH), modified luxol fast blue, and
      Lie's hematoxylin basic fuchsin picric acid (HBFP)] and with immunohistochemistry
      using two antibodies (antimyoglobin and anti-C5b-9). Seventy-five forensic
      autopsy cases were divided into six groups designed to represent successively
      shorter periods of agonal myocardial ischemia: (a) sudden deaths with coronary
      artery disease, macroscopically visible myocardial infarction, and/or fresh
      coronary thrombus; (b) unexplained sudden deaths without coronary artery disease;
      (c) accidental CO poisoning; (d) suicidal CO poisoning in cars; (e) suicidal
      hangings; and (f) instant traumatic deaths, i.e., total brainstem laceration or
      rupture of the thoracic aorta. From each heart, five pieces were removed from
      standardized locations, and six parallel sections were stained with each method
      (i.e., 30 sections from each heart). Hematoxylin-eosin and anti-C5b-9 were only
      positive in the first three groups, thus indicating specificity for intravital
      necrotic changes. The other staining methods were "positive" in one or more cases
      in all six groups, thus implicating a high degree of sensitivity for artifactual,
      agonal ischemic changes. The latter methods cannot be used alone in the diagnosis
      of myocardial infarction. By staining parallel sections with different stains and
      antibodies, it seems possible to estimate the relative length of the agonal
      period in cardiac and noncardiac deaths.

PMID- 9185935
TI  - Fatal gunshot injury caused by an unusual projectile--a barrel-cleaning brush as
      a tandem bullet.
AB  - The case of a man who committed suicide by shooting himself in the head is
      reported. The rifle used by the decedent had been cleaned with the use of a
      barrel-cleaning brush, which had become detached and had been retained in the
      barrel. The brush together with the usual projectile were propelled into the
      head. A highly unusual radiograph was obtained. The implantation of a barrel
      cleaning brush in the skull has not been reported in the English literature. This
      case is reported because of its unique nature and because of possible
      misinterpretation of an unusual radiological appearance. The potential dangers of
      inadequate care during weapon cleaning are also discussed.

PMID- 9185936
TI  - Testing linkage equilibrium on allelic data between VNTR loci.
AB  - We extend Geisser and Johnson's methods and propose simple tests for linkage
      equilibrium of fragment lengths between VNTR loci. The tests are shown to have
      asymptomatically normal or chi-square null distributions. They are applied to the
      reference databases of Asian populations, including the Hong Kong Chinese,
      Singapore Chinese, Singapore Malays, and Singapore Indians. It seems that there
      is little linkage disequilibrium in the data.

PMID- 9185937
TI  - Cockroach: the omnivorous scavenger. Potential misinterpretation of postmortem
      injuries.
AB  - Interpretation of postmortem injuries, including their differentiation from those
      produced antemortem, may be difficult even for experienced forensic pathologists.
      A variety of animals or insects residing in the death environment may alter the
      appearance of the deceased. Dictyoptera blattaria (the cockroach) is common in
      the residential setting. Three cases of sudden and unexpected infant death are
      presented in which postmortem injuries inflicted by cockroaches initially raised
      concern of nonaccidental injury. The true nature of the lesions was not
      recognized by the people at the death scene and, in one case, observation of neck
      injuries raised suspicion of possible strangulation. In another, the lesions were
      thought to be burns of different ages. Cockroaches are omnivorous scavengers that
      devour keratin. They will bite human flesh in both the living and dead with
      resultant injury. Recognition of cockroach bites will help in the evaluation of
      injuries discovered during child death investigations.

PMID- 9185938
TI  - Unusual presentation of death due to carbon monoxide poisoning. A report of two
      cases.
AB  - Two cases are reported representing opposite ends of the spectrum of death as a
      result of carbon monoxide poisoning from car exhaust fumes. In one case, a women
      was reported to be found dead in bed early in the morning by her husband. The
      cause of her death, established by autopsy, was carbon monoxide poisoning.
      Toxicology examination indicated a car engine as the possible source of carbon
      monoxide. The mode of administration was never established. In the second case, a
      women was found in a car located in her garage with a hose leading from the
      exhaust pipe to the interior of the sealed vehicle. Autopsy revealed negligible
      carboxyhemoglobin saturation of the blood, bilateral infarction of the globus
      pallidus, and extensive bronchopneumonia. It was concluded that inhalation of
      carbon monoxide resulted in sublethal hypoxia with subsequent exhalation of
      carbon monoxide and a delayed death.

PMID- 9185939
TI  - Cyanide Poisoning. Case studies of one homicide and two suicides.
AB  - Deaths from cyanide poisoning are now rare. Three cases are reported--a combined
      suicide and homicide and a suicide--using a cyanide-based pest control poison.

PMID- 9185940
TI  - Sudden cardiac death associated with hypoplasia of the coronary arteries and
      conduction system alteration.
AB  - We present a case of sudden cardiac death in a 24-year-old woman with evidence of
      hypoplasia of the left anterior descending (LAD) and posterior descending (PDA)
      coronary arteries. These vessels averaged 0.7 mm in internal diameter combined,
      in contrast to an average of 2.4 mm in control coronary arteries (p < 0.001). The
      myocardium exhibited areas of acute and chronic ischemic change. Also, the
      cardiac conduction system (CCS) had diffuse cellular enlargement, believed to be
      secondary to ischemia. The cells of the sinoatrial node (SAN) and the Purkinje
      cells of the proximal right bundle branch (RBB) averaged 28.5 and 25.6 microns,
      respectively. These were significantly larger than the SAN cells (21.6 microns, p
      = 0.002) and larger than the Purkinje cells (15.9 microns, p = 0.012) of control
      cases. We report that hypoplastic coronary artery disease is a cause of sudden
      death, is associated with varying degrees of ischemic change in the heart, and
      can be associated with condition system alteration.

PMID- 9185941
TI  - Death in custody due to a colopericardial fistula.
AB  - Death while in custody is a sensitive issue as it has the potential to cause
      legal ramifications and political fall-out, to embarrass the law enforcement
      community, and to incite the general population. Studies of deaths while in
      custody show that natural deaths are much more common than both suicides and
      homicides combined. Studies also indicate that natural deaths cluster in the
      older population, while suicides, on the other hand, occur predominantly in the
      younger population. We present a summary and discussion of a death in custody
      that is unique in several aspects. Contrary to the norm, death in this 18-year
      old male inmate was natural. It was due to a rare complication (colopericardial
      fistula) of a surgical procedure (colonic interposition) performed roughly 16
      years previously. We believe that our case represents the third example of a
      colopericardial fistula and the first to occur following corrective surgery for
      esophageal atresia.

PMID- 9185942
TI  - Noncirrhotic portal vein thrombosis causing sudden unexpected death. A rare cause
      of fatally ruptured esophageal varices.
AB  - Noncirrhotic portal vein thrombosis (PVT) is a rare disease that usually presents
      with small nonfatal "herald bleeding" with low mortality. Classic findings of
      noncirrhotic PVT include esophageal varices, splenomegaly, a normal liver, and an
      organized thrombus of the portal vein. We present a case of previously unreported
      sudden unexpected death from noncirrhotic PVT in an asymptomatic elderly woman,
      review the literature of this entity, and examine the pathophysiology of the
      formation of fatally ruptured varices. The portal vein must be carefully examined
      in all cases where there is no coexisting cirrhosis.

PMID- 9185943
TI  - Isolated adrenocorticotropic hormone deficiency: an autopsy case of adrenal
      crisis. A case report.
AB  - We present a case of fatal adrenal crisis due to isolated adrenocorticotropic
      hormone (ACTH) deficiency. Autopsy revealed each adrenal gland weighed 0.9 g and
      the adrenal cortexes were very thin and atrophic. Additionally, cortisol could
      not be observed in the adrenal cortex by immunohistochemical staining.
      Furthermore, urine cortisol and 17-OHCS concentration had decreased to a very low
      level, 20 mg/L and 0.8 mg/L respectively. The anterior pituitary gland was
      atrophic, and showed fibrosis and lymphocytosis was suspected.
      Immunohistochemically growth hormone (GH)-stained pituitary gland cells were
      observed, but there were no cells stained with anti-ACTH antibody. From the
      history and pathological findings, no other deficiencies of pituitary hormones
      were evident. Therefore, isolated ACTH deficiency was suspected. Furthermore, as
      the thyroid gland showed lymphocytic thyroiditis, is was considered that isolated
      ACTH deficiency was associated with an autoimmune cause. Generally, as patients
      of chronic adrenocortical insufficiency are exposed to stress and, therefore,
      have an increased requirement for glucocorticoids, the blood pressure falls,
      leading to hypovolemic shock called " an adrenal crisis." Without treatment,
      patients die in crisis within several hours. In our case, the deceased had drunk
      alcohol without sleep for 2 days. We believe that the stress of drinking and
      sleeplessness induced adrenal crisis and caused his death.

PMID- 9185944
TI  - Lipomatous hypertrophy of the cardiac interatrial septum.
AB  - A case of lipomatous hypertrophy of the cardiac interatrial septum is reported in
      a 91-year-old man who attempted to commit suicide. The lesion was found
      incidentally at autopsy. Gross examination showed a 3.5-cm mass, yellow and firm.
      Histologic study showed a proliferation of mature fat cells and slightly
      hypertrophic cardiac muscle cells.

PMID- 9185945
TI  - Drowning of a girl with anomaly of the bundle of His and the right bundle branch.
AB  - We report an unusual case of a 17-year-old girl who died in an filled bathtub.
      There were at least two attacks of unconsciousness in her premortem history. In
      April 1994, electrocardiography had shown an incomplete right bundle branch
      block. At autopsy, unspecific signs of drowning and hypoplasia of the terminal
      part of the atrioventricular bundle of His and the right bundle branch within the
      cardiac conduction system were found. There were no other obvious autopsy
      findings related to the sudden death of this girl. In addition, toxicologic
      examination for illegal drugs and alcohol was completely negative. We conclude
      that this might be a rare case of death because of acute decompensation of a
      partial hypoplastic cardiac conduction system with loss of consciousness and
      consequent drowning in the bathtub. This case illustrates the value of an
      extensive pathologic examination of the cardiac conduction system in unexpected
      death of young people.

PMID- 9185946
TI  - Homicide by strangling or dumping with postmortem injuries after heroin
      poisoning?
AB  - During construction work, the corpse of a 33-year-old man, H.L., who had been
      missing for 2 years and 4 months, was found in the cellar of a house. Primary
      findings indicated an attack directed at the throat (hematomas of the soft tissue
      and broken larynx). The owner of the cellar claimed, however, that H.L. had died
      of overdose of heroin and that he had removed the body to avoid trouble with the
      authorities. Morphine poisoning was confirmed by chemical analysis. The case is
      interesting because of (a) the good condition of the corpse after over 2 years,
      (b) macroscopic and microscopic evidence of hematomas of the cervical soft
      tissue, (c) successful chemical analysis providing evidence despite a long time
      since death, and (d) considerations regarding the vitality of injury findings.

PMID- 9185947
TI  - Radiographic comparison of the lumbar spine for positive identification of human
      remains. A case report.
AB  - A comparison of antemortem and postmortem abdominal radiographs showing the
      lumbar spine was used to establish a positive identification of an unknown
      cadaver. A positive matching of similar unique skeletal feature, including large
      osteophytes of the third, fourth, and fifth lumbar vertebrae, distinctive
      features of the spinous and transverse processes, and identical angulation of an
      existing right lumbar scoliosis was established. A criticism of the methods used
      to establish the identification is presented.

PMID- 9185948
TI  - In memoriam: Mary Douglas Leakey (1913-1996).

PMID- 9185949
TI  - Social context and psychosocial influences on blood pressure among American
      Samoans.
AB  - This study explores social and explores social and economic influences on health
      within a model formulated to address explicitly both individual and household
      level phenomena. Dressler's lifestyle incongruity model is used as a basis from
      which to predict the effects of intracultural contexts of variability on blood
      pressure. The sample for this survey consists of 134 Samoan men and women living
      in American Samoa. Based on previous experience and ethnographic sources, two key
      intracultural contexts were examined; gender, i.e., male-female differences in
      response to psychosocial stress, and household employment as indicated by whether
      or not both spouses in a household are employed. Our analysis indicates that
      lifestyle incongruity, defined as the difference between the material culture
      presented by a household and the economic resources of the family, is
      significantly associated with both systolic and diastolic blood pressure.
      Furthermore, males and females show opposite blood pressure associations with
      both lifestyle incongruity (male blood pressure increases with increasing
      incongruity while female blood pressure does not) and household employment (male
      blood pressure is higher when both spouses work but female blood pressure is
      lower).

PMID- 9185950
TI  - Growth, development, and sexual dimorphism in vervet monkeys (Cercopithecus
      aethiops) at four sites in Kenya.
AB  - Body weight and ten body segment measurements were collected from 367 wild
      trapped vervet monkeys (Cercopithecus aethiops) in central and southern Kenya.
      The animals represent between 70 and 95% of the animals in each of 30 troops at
      four geographical locations separated by 80 to 380 km. The capture sites differed
      in altitude, mean annual rainfall and temperature. Two questions are addressed:
      (1) what are the differences in male and female growth patterns, and (2) what is
      the relationship between size, climate, and availability of food? Each animal was
      assigned to an age class based on dental examination. Means for all variables do
      not diverge for males and females from birth to age class 4 (15-18 months). After
      this, male and female growth rates diverge. This sexual dimorphism in growth
      pattern may reflect timing of entry into the reproductive community. A nested
      analysis of variance (ANOVA) was employed to compare sites, groups within sites
      and individuals within groups. Statistically significant differences between
      sites in body weight and body segment measurements are found for adult females.
      Except for tail length, these differences do not follow Bergmann's or Allen's
      Rules correlating size differences and temperature, but rather may reflect
      proximity to cultivated areas or tourist lodges with greater access to human
      food.

PMID- 9185951
TI  - Intrasexual competition and body weight dimorphism in anthropoid primates.
AB  - Body weight dimorphism in anthropoid primates has been thought to be a
      consequence of sexual selection resulting from male-male competition for access
      to mates. However, while monogamous anthropoids show low degrees of weight
      dimorphism, as predicted by the sexual selection hypothesis, polygynous
      anthropoids show high variation in weight dimorphism that is not associated with
      measures of mating system or sex ratio. This observation has led many to debate
      the role of other factors such as dietary constraints, predation pressure,
      substrate constraints, allometric effects, and phylogeny in the evolution of
      anthropoid weight dimorphism. Here, we re-evaluate variation in adult body weight
      dimorphism in anthropoids, testing the sexual selection hypothesis using
      categorical estimates of the degree of male-male intrasexual competition
      ("competition levels"). We also test the hypotheses that interspecific variation
      in body weight dimorphism is associated with female body weight and categorical
      estimates of diet, substrate use, and phylogeny. Weight dimorphism is strongly
      associated with competition levels, corroborating the sexual selection
      hypothesis. Weight dimorphism is positively correlated with increasing female
      body weight, but evidence suggests that the correlation reflects an interaction
      between overall size and behavior. Arboreal species are, on average, less
      dimorphic than terrestrial species, while more frugivorous species tend to be
      more dimorphic than folivorous or insectivorous species. Several alternative
      hypotheses can explain these latter results. Weight dimorphism is correlated with
      taxonomy, but so too are competition levels. We suggest that most taxonomic
      correlations of weight dimorphism represent "phylogenetic niche conservatism";
      however, colobines show consistently low degrees of weight dimorphism for reasons
      that are not clear.

PMID- 9185952
TI  - Stable isotope ratios indicate diet and habitat use in New World monkeys.
AB  - This paper demonstrates the use of stable isotope ratios of carbon and nitrogen
      in animal tissue for indicating aspects of species behavioral strategy. We
      analyzed hair from individuals representing four species of New World monkeys
      (Alouatta palliata, the mantled howler; Ateles geoffroyi, the spider monkey;
      Cebus capucinus, the capuchin; and Brachyteles arachnoides, the woolly-spider
      monkey or muriqui) for delta 13C and delta 15N using previously developed
      methods. There are no significant differences in either carbon or nitrogen ratios
      between sexes, sampling year, or year of analysis. Seasonal differences in delta
      13C reached a low level of significance but do not affect general patterns.
      Variation within species was similar to that recorded previously within single
      individuals. The omega 13C data show a bimodal distribution with significant
      difference between the means. The two monkey populations living in an evergreen
      forest were similar to each other and different from the other two monkey
      populations that inhabited dry, deciduous forests. This bimodal distribution is
      independent of any particular species' diet and reflects the level of leaf cover
      in the two types of forest. The delta 15N data display three significantly
      different modes. The omnivorous capuchins were most positive reflecting a trophic
      level offset. The spider monkeys and the muriquis were similar to one another and
      significantly more positive than the howlers. This distribution among totally
      herbivorous species correlates with the ingestion of legumes by the howler monkey
      population. In combination, these data indicate that museum-curated primate
      material can be analyzed to yield information on forest cover and diet in
      populations and species lacking behavioral data.

PMID- 9185953
TI  - Hindlimb suspension and hind foot reversal in Varecia variegata and other
      arboreal mammals.
AB  - The foot, perhaps more than any other region of the primate body reflects the
      interaction of positional behaviors with the geometric properties of available
      supports. The ability to reverse the hind foot during hindlimb suspension while
      hanging from a horizontal support or descending a large diameter vertical trunk
      has been noted in many arboreal mammals, including primates. Observations of
      Varecia variegata in the wild and under seminatural conditions document hindlimb
      suspension in this lemurid primate. The kinematics and skeletal correlates of
      this behavior are examined. Analogy is made with the form and function exhibited
      by nonprimate mammalian taxa employing this behavior. Examples of carnivores and
      rodents display very similar adaptations of the tarsals while other mammals, such
      as the xenarthrans, accomplish a similar end by means of different morphologies.
      However, a suite of features is identified that is shared by mammals capable of
      hind foot reversal. Hindlimb suspension effectively increases the potential
      feeding space available to a foraging mammal and represents a significant, and
      often unrecognized, alternative adaptive strategy to forelimb suspension and
      prehensile-tail suspension in primates.

PMID- 9185954
TI  - Fueguian cranial morphology: the adaptation to a cold, harsh environment.
AB  - Craniometric data from the three extinct tribes that inhabited Tierra del Fuego
      (Selk'nam, Yamana, and Kaweskar) were gathered following Howell's measurement
      technique. We studied 180 skulls preserved at thirteen different institutions.
      Analysis of variance (ANOVA) between groups showed that morphological
      similarities among Fueguian groups are far more important than some differences
      between marine (Yamana and Kaweskar) and terrestrial (Selk'nam) groups. A
      principal component analysis (PCA) generated from the correlation matrix shows
      that Fueguians fall as outliers with respect to the typical Mongoloid morphology.
      In addition, a UPGMA tree generated from a squared Euclidean distance matrix
      indicates that Fueguian groups have a morphological pattern that is very distinct
      from that of other present-day Amerindian groups, with the exception of the
      Eskimos. One of the variables that contributes substantially to the
      differentiation of Eskimos and Fueguians is the nasal height. This suggests that
      nasal morphology in both groups could be a response to adaptive pressures related
      to the cold environment. However, other morphological particularities of Fueguian
      skulls, such as craniofacial robustness and variables of craniofacial width, can
      be attributed to a large masticatory stress. As a whole, the morphological
      features of Fueguian groups can be regarded as a general adaptive response to a
      very harsh environment, along with the retention of some plesiomorphic features.
      Assuming that the initial entry in Tierra de Fuego took place around 10,000 years
      BP, before the disappearance of the last land bridges in the Magellan Straits,
      then this adaptation might have arisen in a relatively short period, hastened by
      the extreme environmental conditions.

PMID- 9185955
TI  - External auditory exostosis in prehistoric Chilean populations: a test of the
      cold water hypothesis.
AB  - Over one thousand prehistoric crania (n = 1,149) from northern Chile were
      analyzed to determine if the presence of external auditory exostosis (EAE) was a
      type of subsistence-induced pathology, a consequence of habitual fishing in the
      cold water of the Pacific Ocean, rather than genetically determined. To test this
      occupational hypothesis, the sample was divided according to chronology, type of
      economy, site elevation, and sex. The crania came from 43 sites, including the
      coast, lowland valleys (100-2,000 m), and highlands (2,000 to 4,000 m) with a
      time frame of 7,000 B.C. to the Inca era (1500 A.D.). There was a significant
      association between EAE, environment, and sex. The coastal inhabitants had the
      highest prevalence of EAE with 30.7% (103/336), followed by 2.3% (6/24) for the
      valley people and 0% (0/549) for highlanders. Coastal and valley men were
      significantly more affected than their female counterparts. Contrary to
      expectations, there was no significant association between EAE and economy and/or
      chronology. In the Arica area, the early Chinchorro fishers, without agriculture,
      had 27.7% (26/94) EAE, the subsequent agro-pastoralists, 42.7% (32/75), and the
      late Arican agro-pastoral fishers had 35.6% (36/101) EAE. Apparently, with the
      advent of agriculture, the coastal Arican populations increased their ocean
      harvests, rather than decreased them, to gain a surplus in order to trade with
      nonmaritime groups.

PMID- 9185956
TI  - Capuchin monkey (Cebus apella) grips for the use of stone tools.
AB  - This research examined capuchin monkey (Cebus apella) grips for the use of
      throwing, nut-cracking and cutting tools. We provided subjects with stones and
      apparatus that accommodated the use of stones as tools. Our subjects exhibited
      five grips, two of which the animals used when force was the primary
      consideration (power grips) and three of which the animals used when accuracy of
      sensory judgment and instrumentation was required (precision grips). We believe
      that the range of contexts in which capuchins use stone tools, combined with the
      ability of capuchins to employ both power and precision grips as part of their
      tool repertoire, indicate that Cebus apella can be used to identify grips that
      facilitated hominid lithic technology.

PMID- 9185957
TI  - Ecogeographical patterning and stature prediction in fossil hominids: component
      on M.R. Feldesman and R.L. Fountain, American Journal of Physical Anthropology
      (1996) 100:207-224.

PMID- 9185958
TI  - Request for disclosure of financial interest.

PMID- 9185959
TI  - Additional research on tendon strains and stresses.

PMID- 9185960
TI  - Influence of type and breed of horse on serum osteocalcin concentration, and
      evaluation of the applicability of a bovine radioimmunoassay and a human
      immunoradiometric assay [corrected].
AB  - OBJECTIVES: To evaluate applicability of a human osteocalcin (OC)
      immunoradiometric assay (IRMA) for use with equine serum and compare it with a
      bovine radioimmunoassay (RIA) previously proven valid for such samples, and to
      describe the effect of type and breed of horses on serum OC concentration.
      ANIMALS: 100 healthy horses of either sex, classified as type I or II (draught or
      warmblood, respectively). Each type was represented by 2 breed groups, each
      comprising 25 horses. PROCEDURE: Blood samples were collected in the morning, and
      the serum was separated. Osteocalcin was measured, using commercially available
      RIA and IRMA kits, according to the manufacturer's instructions. All samples were
      evaluated in duplicate. RESULTS: The human IRMA did not recognize equine OC.
      Significant variations in the bovine RIA results were observed between types of
      horses. Draught horses had lower OC concentration, compared with warmblood
      horses. Significant difference was not observed between breeds for type of horse.
      Sex had no influence on serum OC values, but age was a significant covariable for
      both types of horses. CONCLUSIONS: No crossreactivity exists between the equine
      and human amino- and/or carboxy-terminus of OC, using this particular human IRMA
      kit. Difference in blood OC concentration exists between draught and warmblood
      types of horses. CLINICAL RELEVANCE: Use of this human IRMA kit is not valid for
      equine serum. Horse type must be taken into account when evaluating OC
      concentration in research or clinical situations, especially if small variations
      in OC concentration are expected.

PMID- 9185962
TI  - Purification and characterization of bovine complement component C3 and its
      cleavage products.
AB  - OBJECTIVE: To purify complement component C3 from bovine serum, characterize and
      analyze NH2-terminal amino acid sequences from its various cleavage products, and
      do cross-species homology comparisons. ANIMALS: 2 healthy lactating Holstein
      cows, and 2 healthy adult female New Zealand White rabbits. PROCEDURE: Bovine C3
      was isolated from serum, and was cleaved to C3b. The resulting protein was
      analyzed to determine apparent molecular mass of resulting protein segments.
      Bands were electroblotted onto a membrane and excised, then NH2-terminal amino
      acid sequences were determined. RESULTS: The C3 preparation consisted of 6
      segments, with molecular mass of 30, 40 (2 bands, a and b), 70, 75, and 115 kd.
      Via sequence comparisons, the 115-kd band was identified as the alpha chain; the
      75-kd segment was determined to be the NH2-terminal portion of alpha chain; the
      70-kd piece was identified as the intact beta chain; and the two 40-kd bands are
      believed to be located at the C-terminal portion of the alpha chain, at the
      cleavage site that yields C3f. The 30-kd band is the NH2-terminal portion of the
      alpha chain (minus the C3a segment). Sequence analysis of each band revealed a
      high degree of homology with human, rat, mouse, and horse C3. Polyclonal
      antibodies raised in rabbits yielded sera that reacted to the purified sample in
      manner similar to that of commercially available antibodies. CONCLUSIONS: The
      purified preparation contained intact C3, C3b, and the degradation products iC3b
      and C3c, which had high sequence homology with those of other species. The C3a
      and C3d, and C3g segments of protein were not detected and may have been lost
      during purification, lyophilization, or transfer steps. Structure and cleavage
      characteristics of bovine C3 can be used to better understand immune responses to
      bacterial pathogens in the mammary gland.

PMID- 9185961
TI  - Immortalization of caprine fibroblasts permissive for replication of small
      ruminant lentiviruses.
AB  - OBJECTIVE: To establish immortalized caprine fibroblastic cell lines permissive
      for replication of small ruminant lentiviruses. ANIMALS: Carpal synovial membrane
      explants collected aseptically from a surgically delivered fetus of a lentivirus
      seronegative goat. PROCEDURE: Immortalization of goat embryonic fibroblasts was
      performed by DNA transfection with plasmids coding for simian virus 40 large T
      antigen. The generated cell lines were phenotypically characterized.
      Cytogenetics, growth pattern, and sensitivity to viral infection were studied.
      RESULTS: 3 cell lines, designated TIGEF, mMTSV-54, and mMTSV-93, were generated.
      They had a more rapid doubling time than did fibroblasts from which they were
      derived, and retained morphologic and phenotypic fibroblastic characteristics.
      They were immortalized but not transformed because tumor formation was not
      promoted after their s.c. injection into athymic nude mice. The 3 cell lines were
      susceptible to caprine arthritis-encephalitis virus and visna-maedi virus
      infections, and supported a complete virus replication cycle. CONCLUSIONS:
      Cultured caprine fibroblastic cells were immortalized, using simian virus 40
      large T antigen. The TIGEF, mMTSV-54, and mMTSV-93 immortalized cell lines were
      permissive to in vitro small ruminant lentivirus replication. CLINICAL RELEVANCE:
      Because lentivirus detection, as well as detailed studies of host-lentivirus
      interactions, are hampered by differences in viral susceptibility of each primary
      culture, permanent cell lines are essential tools for such analysis.

PMID- 9185963
TI  - Protective vaccination of ferrets against canine distemper with recombinant pox
      virus vaccines expressing the H or F genes of rinderpest virus.
AB  - OBJECTIVE: To investigate the ability of rinderpest virus (RPV) antigens,
      expressed in pox virus vectors, to protect against canine distemper virus (CDV)
      infection in ferrets. ANIMALS: Ferrets (Mustela putorius; n = 27) with no
      previous exposure to CDV. PROCEDURE: Ferrets were inoculated intradermally with
      recombinant vaccinia viruses expressing the H gene of RPV, the F gene of RPV, the
      H and F genes of RPV, or fowlpox virus recombinant expressing both genes. Two
      ferrets were vaccinated s.c. with CDV vaccine as positive controls, and 1 group
      was left unvaccinated as a negative control. Blood was obtained from ferrets
      biweekly; antibody titer to RPV was detected by ELISA, and CDV antibody titer was
      measured by serum neutralization testing and ELISA. RESULTS: Partial protection
      was seen in all groups, with vRVFH vaccination being the most protective (60%).
      CONCLUSIONS AND CLINICAL RELEVANCE: A single inoculation with a vaccinia virus
      expressing the H and F genes of RPV was able to protect 60% of the vaccinated
      ferrets challenge exposed with a high dose of CDV. These results indicate the
      ability of RPV antigens expressed by vaccinia virus to protect ferrets against a
      related morbillivirus. Further, they document the safety and efficacy of a
      recombinant vaccinia virus vaccine for ferrets. Such vaccines may be useful given
      the susceptibility of ferrets to CDV and the problem of maternal antibody
      interfering with vaccination of young animals.

PMID- 9185964
TI  - Effect of growth hormone or chromium picolinate on swine metabolism and
      inflammatory cytokine production after endotoxin challenge exposure.
AB  - OBJECTIVE: To determine whether recombinant porcine somatotropin (PST) or
      chromium picolinate (CrP) affected cytokine production and metabolism in swine
      after endotoxin challenge exposure. ANIMALS: 20 Poland China X Landrace pigs,
      5/group. PROCEDURE: Pigs were given CrP-supplemented feed at body weight of 20
      kg; PST treatment began at 60 kg, and both treatments continued through body
      weight of 90 kg. At 90 kg, pigs were challenge exposed with 20 micrograms of
      lipopolysaccharide (LPS)/kg of body weight. Blood samples were obtained at
      various times through 24 hours after LPS challenge exposure. RESULTS: In all pigs
      not given PST, glucose concentration decreased 2 to 4 hours after LPS. In PST
      treated pigs, blood glucose concentration was decreased at 6 to 8 hours after
      LPS. Plasma insulin concentration paralleled changes in glucose concentration.
      Nonesterified fatty acid concentration was high 2 to 24 hours after LPS in pigs
      not given PST and at 6 to 24 h in PST-treated pigs. Plasma urea nitrogen
      concentration was high at 6 to 24 hours after LPS in pigs not given PST. The urea
      nitrogen values in PST-treated pigs were lower at all times. Serum aspartate
      transaminase activity was high 6 to 24 hours after LPS in pigs not given PST,
      whereas PST treatment prevented the increase in this enzyme activity. In
      untreated (PST) pigs, plasma bilirubin (total and direct) concentrations were
      high 4 to 8 hours after LPS and returned to normal at 24 hours. The PST- and CrP
      treated pigs maintained normal plasma bilirubin concentrations. Interleukin 6
      activity was unaffected by CrP and PST treatments. Treatment with CrP and PST
      decreased the tumor necrosis factor alpha response to LPS, compared with that in
      control pigs. CONCLUSIONS: PST, and to a lesser extent CrP, provide protection
      against the adverse metabolic effects of LPS-induced septic shock.

PMID- 9185965
TI  - Resazurin reduction as a function of respiratory burst in bovine neutrophils.
AB  - OBJECTIVE: To determine whether the respiratory burst of neutrophils from bovine
      blood and milk can be analyzed by use of a fluorometric resazurin reduction
      assay. SAMPLE POPULATION: Neutrophils were obtained from EDTA-anticoagulated
      blood of 7 dairy cows. Neutrophils also were isolated from milk samples of a cow
      intramammarily challenge exposed with Escherichia coli lipopolysaccharide.
      PROCEDURE: The respiratory burst of neutrophils was analyzed in parallel, using
      the conventional luminol-enhanced luminometric procedure and a novel fluorometric
      procedure with resazurin as the fluorogenic substrate. Opsonized zymosan and
      phorbol myristate acetate were used as stimulants. The mechanism of the
      fluorescent response was analyzed, using metabolic inhibitors to various cell
      functions. Luminometry and fluorometry were carried out in parallel, using
      microtitration tray-reading instruments. RESULTS: Stimulation of neutrophils
      induced resazurin reduction to resorufin and a fluorescent response. The
      luminescent response was transient, but the fluorescent response (build-up of
      fluorescent resorufin) was cumulative. Therefore, a single end-point measurement
      can be used for the fluorometric assay. CONCLUSIONS: The proposed fluorometric
      microtitration tray technology is simple and has a high throughput capacity. The
      fluorometric and luminometric assays seem to have similar potential in the
      analysis of phagocyte functions.

PMID- 9185966
TI  - Pathogenesis of infection induced by an adenovirus isolated from a goat.
AB  - OBJECTIVE: To determine the pathogenic potential of an adenovirus isolated from a
      goat. ANIMALS: 14 colostrum-deprived, isolation-reared goat kids approximately 3
      weeks old. PROCEDURE: Kids were inoculated with either cell culture fluid
      containing adenovirus (n = 10) or uninfected cell culture fluid (n = 4): 2 ml
      transtracheally and 1 ml/nostril. Clinical signs of disease and rectal
      temperature were recorded daily; nasal secretion and fecal specimens were
      collected daily. Control kids were necropsied, 2/d, on postinoculation days (PID)
      5 and 10. Virus-inoculated kids were necropsied on PID 3, 5, 7, 10, and 28. After
      necropsy, lung, liver, kidney, and brain specimens were aseptically collected for
      virus isolation attempts. Tracheal fluid was collected on sterile cotton swabs.
      Turbinate, trachea, lung, mediastinal lymph node, liver, kidney, duodenum,
      jejunum, ileum, mesenteric lymph node, colon, and brain specimens were collected
      for histologic evaluation. RESULTS: Kids developed mild-to-moderate clinical
      respiratory tract infection. Virus was recovered consistently from nasal
      secretion and sporadically from fecal specimens. Grossly, there were multiple
      areas of atelectasis and hyperemia, principally in the cranioventral portion of
      the lungs. Microscopically, there was detachment and sloughing of foci of
      epithelial cells of the terminal bronchioles and alveoli. In kids necropsied late
      in the disease, these changes were accompanied by hyperplasia of type-II
      epithelial cells. Viral inclusions were not an obvious feature, but a few cells
      contained probable inclusions. CONCLUSIONS AND CLINICAL RELEVANCE: The caprine
      adenovirus reported here is capable of inducing respiratory tract disease and
      lesions in the lungs of young kids.

PMID- 9185967
TI  - Nematocidal efficacy of eprinomectin, delivered topically, in naturally infected
      cattle.
AB  - OBJECTIVE: To assess the nematocidal efficacy of eprinomectin in naturally
      infected cattle. ANIMALS: 62 (31 eprinomectin-treated and 31 control) beef mixed
      breed or Holstein cattle, either 6 to 11 or 48 to 96 months old. PROCEDURE:
      Cattle were housed 21 to 27 days before treatment to allow parasites to reach
      maturity. Animals were grouped by sex, ranked by weight, and randomly assigned to
      treatment group. Fecal flotation was done to identify cattle with intestinal
      nematode infections. Treatment groups were: 1--eprinomectin topical vehicle (1
      ml/10 kg) and 2--eprinomectin topical solution (1 ml/10 kg). Cattle were
      euthanatized by replicate on day 14 or 15, and standard procedures were used to
      recover of pulmonary, abomasal, small intestinal, and large intestinal nematodes.
      RESULTS: Eprinomectin efficacy across all trials was 100% against adult
      Trichostrongylus axei, Haemonchus placei, Oesophagostomum radiatum, and
      Dictyocaulus viviparus, as well a fourth-stage larval Oes radiatum, Ostertagia
      ostertagi, Nematodirus helvetianus, and Cooperia spp. Efficacy against adult O
      ostertagi, Cooperia oncophora, C punctata, C surnabada, C spatulata, N
      helvetianus, Trichuris sp, and Trichuris fourth-stage larvae was 99.9 and 99.8,
      99.6, 98.9, 98.3, 99.7, 97.8, and 84.3%, respectively. All results were
      significant (P < 0.01) except those for C spatulata. Adverse reactions were not
      observed. CONCLUSION AND CLINICAL RELEVANCE: Eprinomectin is a safe and effective
      nematocide against naturally acquired nematode infections in cattle when
      administered at a dosage of 500 micrograms/kg. Milk and meat withholding is not
      necessary when using this product.

PMID- 9185969
TI  - Identification of beta-adrenergic receptor subtypes mediating relaxation in
      isolated equine ileum.
AB  - OBJECTIVE: To identify beta-adrenergic receptor subtypes in ileum smooth muscle
      of the horse. SAMPLE POPULATION: Isolated strips of equine longitudinal ileum
      smooth muscle and membrane preparations from smooth muscle of the intestinal
      wall. PROCEDURE: Functional assays and radioligand binding assays. RESULTS:
      Relaxation of ileum longitudinal smooth muscle proved to be mainly caused by
      stimulation of beta-atypical and beta 2-adrenergic receptors. Binding studies on
      cell membranes indicated that the total beta-adrenergic receptors population
      consists of 54% beta-atypical, 34% beta 2- and 12% beta 1-subtypes. CONCLUSIONS:
      The data suggest that sympathetic relaxation of equine ileum smooth muscle
      depends mainly on beta-atypical receptor subtypes activation, with a minor
      contribution by beta 2-subtypes. CLINICAL RELEVANCE: The important role of beta
      atypical adrenergic receptor subtypes in the relaxation of equine ileum suggests
      possible clinical use of selective beta-atypical receptor agonists to control
      intestinal disturbances.

PMID- 9185968
TI  - Chromogranin A plasma concentration and expression in pancreatic islet cell
      tumors of dogs and cats.
AB  - OBJECTIVES: To describe expression of the neuroendocrine marker chromogranin A
      (CgA) in canine and feline pancreatic islet cell tumors and their metastases, and
      to evaluate plasma CgA concentration in dogs and cats with insulinoma. SAMPLE
      POPULATION: Paraffin-embedded tissues from 25 canine and 2 feline pancreatic
      islet cell tumors, 5 canine and 6 feline exocrine pancreatic tumors, and normal
      pancreatic tissue from 2 dogs and 2 cats. Heparinized plasma samples from 3 dogs
      and 2 cats diagnosed with insulinoma, and 10 control plasma samples from each
      species. PROCEDURE: Immunohistochemical analysis was performed on the 42 tissue
      specimens, using antisera against CgA, neuron-specific enolase, insulin,
      somatostatin, glucagon, and pancreatic polypeptide. The 25 plasma samples were
      evaluated, using a soluble-phase, double-antibody, equilibrium radioimmunoassay
      directed against the amino- and carboxy-terminal peptides of bovine CgA. RESULTS:
      Chromogranin A expression was found in 76% of canine and 2 of 2 feline pancreatic
      islet cell tumors. Of 7 animals with CgA immunoreactivity in primary tumors, 6
      also had CgA immunostaining of metastatic lesions. Plasma CgA concentration in 2
      dogs with insulinoma (0.9, 1.0 ng/ml) exceeded the reference range established
      for 10 clinically normal control dogs (0.50 +/- 0.16 ng/ml). Feline plasma CgA
      samples had extensive nonspecific background immunoreactivity. CONCLUSIONS:
      Chromogranin A is a useful immunohistochemical marker for pancreatic tumors of
      neuroendocrine origin and their metastases. Plasma CgA concentration determined
      by radioimmunoassay was high in 2 dogs with insulinoma. CLINICAL RELEVANCE:
      Immunohistochemical staining of tissues or cytologic specimens for CgA and/or
      neuron-specific enolase may help distinguish masses of unknown origin as
      neuroendocrine in nature. Increase in plasma CgA concentration may be useful
      diagnostically for animals with suspected neuroendocrine tumors.

PMID- 9185971
TI  - Effect of furosemide and subsequent intravenous fluid administration on right
      atrial pressure of splenectomized horses.
AB  - OBJECTIVE: To investigate the effect of i.v. administration of fluids on the
      furosemide-induced reduction in right atrial pressure (RAP) and relative change
      in blood volume (BV) of splenectomized mares. ANIMALS: 5 splenectomized mares.
      PROCEDURE: RAP was measured by use of a micromanometer placed in the right
      atrium. Jugular venous blood was collected for measurement of hematocrit, plasma
      total protein concentration, and hemoglobin concentration. Right atrial pressure
      was recorded and blood samples were collected immediately before furosemide (1
      mg/kg of body weight, i.v.) administration, then every 15 minutes for 240
      minutes. Beginning 120 minutes after furosemide administration, polyionic fluids
      (lactated Ringer's solution) were administered (2 L q 15 min) for 120 minutes.
      RESULTS: Furosemide induced a significant (P < 0.05) decrease in mean RAP (7.6 +/
      1.5 and 3.2 +/- 1.2 mm of Hg before and 15 minutes after furosemide
      administration, respectively), and BV (8.4 +/- 1.1 % by 15 minutes). Polyionic
      fluid administration restored RAP and BV. The volume of polyionic fluids
      administered (32 +/- 2 ml/kg) was not significantly different from the volume of
      urine produced (38 +/- 7.8 mg/kg). Difference was not apparent in the relation
      between change in BV and RAP before or after fluid administration. CONCLUSIONS:
      The effect of furosemide on RAP of horses is mediated in large part by furosemide
      induced reduction in BV. However, an effect of furosemide on venous compliance
      cannot be excluded as contributing to the reduction in RAP.

PMID- 9185970
TI  - Kinetic gait analysis assessment of meloxicam efficacy in a sodium urate-induced
      synovitis model in dogs.
AB  - OBJECTIVE: To examine the ability of meloxicam, a cyclooxygenase inhibitor, to
      mediate the effects of sodium urate-induced acute stifle synovitis in dogs.
      ANIMALS: 12 clinically normal adult hound-type dogs. PROCEDURE: A blinded,
      randomized, controlled single crossover design study was performed to determine
      the efficacy of meloxicam, using 2 dosage groups. In 2 experimental phases, dogs,
      according to group, received meloxicam (0.1 or 0.5 mg/kg of body weight) or
      matched volume of meloxicam vehicle, with a washout period of 21 to 28 days
      between phases. Blood samples for hematologic and biochemical analysis, as well
      as synovial fluid or cytologic analysis, were collected immediately before and
      approximately 24 hours after articular challenge of dogs under propofol
      anesthesia. Ground reaction forces (GRF) and subjective clinical scores were
      determined before and at 4, 8, 12, and 24 hours after articular challenge.
      Vertical force data included peak force, impulse, limb loading, and unloading
      rates. Craniocaudal data were divided into braking and propulsion phases and
      consisted of peak force and associated impulses. RESULTS: Except for propulsion
      impulse at 24 hours, all GRF variables were significantly greater at all post
      synovitis induction times in the group receiving the high meloxicam dose.
      Significant differences in all GRF variables were seen at various times between
      the low-dose meloxicam group and the corresponding control group, and between the
      low- and high-dose meloxicam groups. Similar significance was seen in the
      subjective clinical evaluations. Strong correlations existed between the
      subjective and objective data. CONCLUSIONS: Meloxicam was effective in
      attenuating the effects of sodium urate-induced acute synovitis in dogs. Kinetic
      gait data provided an objective measurement of lameness in an experimentally
      induced arthritis model and quantified lameness improvements in response to
      medication with a nonsteroidal anti-inflammatory drug.

PMID- 9185972
TI  - Pharmacokinetics of phenylbutazone in camels.
AB  - OBJECTIVE: To document disposition variables of phenylbutazone and its
      metabolite, oxyphenbutazone, in camels (Camelus dromedarius) after single i.v.
      bolus administration of phenylbutazone, with a view to making recommendation on
      avoiding violative residues in racing camels. ANIMALS: 6 healthy camels (4 males,
      2 females), 5 to 7 years old, and weighing from 350 to 450 kg. PROCEDURE: Blood
      samples were collected to 0, 5, 10, 15, 45, and 60 minutes and at 1.5, 2, 2.5, 3,
      3.5, 4, 5, 6, 8, 12, 24, 26, 28, 30, 40, 48, 50, 53, and 60 hours after i.v.
      administration of 4.5 mg of phenylbutazone per kg of body weight. Urine was
      obtained in fractions during the entire blood sample collection period. Serum and
      urine phenylbutazone concentrations were measured by high-performance liquid
      chromatography; assay sensitivity was 100 ng/ml. Serum oxyphenbutazone
      concentration was measured by gas chromatography/mass spectrometry; assay
      sensitivity was 10 ng/ml. RESULTS: Disposition of phenylbutazone was best
      described by a two-compartment open model. Mean +/- SEM elimination half-life was
      13.44 +/- 0.44 hours. Total body clearance was 12.63 +/- 1.64 mg/kg/h. Renal
      clearance was between 0.3 and 0.4% of total body clearance. The elimination half
      life of oxyphenbutazone was 23.9 +/- 2.09 hours. CONCLUSIONS: The elimination
      half-life and total body clearance of phenylbutazone in camels are intermediate
      between reported values in horses and cattle. Extrapolation of a dosage regimen
      from either species to camels is, therefore, not appropriate. Elimination of
      phenylbutazone in camels is mainly via metabolism. Owing to the long half-life of
      phenylbutazone and of oxyphenbutazone, and to the zero drug concentration
      regulation adopted by the racing commissioner in the United Arab Emirates,
      practicing veterinarians would be advised not to use phenylbutazone in camels for
      at least 7 days prior to racing.

PMID- 9185973
TI  - Effects of sedation, anesthesia, and endotracheal intubation on respiratory
      mechanics in adult horses.
AB  - OBJECTIVE: To determine the effects of endotracheal intubation on respiratory
      mechanics during xylazine sedation and xylazine-diazepam-ketamine anesthesia in
      adult horses. ANIMALS: 5 healthy adult horses. PROCEDURE: Measurements were
      derived from recordings of respiratory gas flow, and transpulmonary and
      transtracheal pressures. Total pulmonary resistance (RT) was partitioned into
      upper airway resistance (extrathoracic portion of trachea, larynx, pharynx, nasal
      cavity, nares; RUA) and lower airway resistance (intrathoracic portion of
      trachea, bronchi, bronchioles). Baseline measurements were obtained in unsedated
      horses, after xylazine administration, and following nasotracheal intubation (ID,
      18 mm). Measurements were obtained following induction of xylazine-diazepam
      ketamine anesthesia and subsequent to endotracheal intubations (ID, 22, 20, and
      16 mm). During recovery, horses were nasotracheally intubated (ID, 18 mm).
      Measurements were obtained upon standing, and repeated after extubation. Data
      were examined by use of ANOVA with repeated measures. RESULTS: Significant
      increases in mean work of breathing (W), RT, and RUA observed with xylazine
      sedation were variably attenuated by nasotracheal intubation. During xylazine
      diazepam-ketamine anesthesia, the highest mean values for W, RT, RUA,
      transpulmonary and transtracheal pressures developed during non-intubation
      periods. The magnitudes of resistance and pressure values were inversely
      proportional to the internal diameter of the endotracheal tube. At recovery,
      values of the W and all measurements of resistances and pressures were
      significantly increased, compared with presedation values. Extubation resulted in
      further increases in these measurements. CONCLUSIONS: Work of breathing in horses
      is substantially increased when RUA is increased during xylazine sedation and
      xylazine-diazepam-ketamine anesthesia. Endotracheal intubation reduces W by
      reducing RUA.

PMID- 9185974
TI  - Effects of certain vasoactive agents on the long-term pattern of blood pressure,
      heart rate, and motor activity in cats.
AB  - OBJECTIVE: To determine whether a diurnal pattern exists in cardiovascular
      variables and motor activity, and whether pharmacologic agents that decrease
      (angiotensin converting enzyme inhibitor) or increase (N omega-nitro-L-arginine
      methyl ester [L-NAME]) blood pressure alter the pattern. ANIMALS: 6 clinically
      normal cats. PROCEDURE: Radiotelemetric implants were used to measure systemic
      arterial pressure, heart rate, and motor activity in conscious cats maintained in
      cages. Measurements were obtained during absence of treatment (control),
      treatment with dietary salt restriction plus an inhibitor of angiotensin
      converting enzyme (2.5 mg of lisinopril, PO, daily) and treatment with an
      inhibitor of nitric oxide production (0.1% L-NAME in the drinking water).
      RESULTS: A diurnal pattern in arterial pressure and motor activity was observed,
      with highest values obtained during presence of laboratory personnel. Mean values
      of arterial pressure obtained during light hours varied from those obtained
      during darkness (P < 0.05), but by < 3 mm of Hg. Dietary sodium restriction did
      not have an appreciable effect on arterial pressure, but the combined
      administration of a low sodium diet plus lisinopril decreased (P < 0.05) measured
      indices of arterial pressure. Administration of L-NAME increased arterial
      pressure (P < 0.05) and altered its diurnal pattern. CONCLUSIONS: Although a
      diurnal pattern of arterial pressure was observed, variations were mostly
      associated with presence of human beings. Administration of L-NAME, but not
      lisinopril, altered this diurnal pattern. CLINICAL RELEVANCE: Factors that modify
      arterial pressure may alter the diurnal pattern of cardiovascular variables. In
      measuring arterial pressure in cats, the effects of human contact may
      artifactually increase such variables.

PMID- 9185975
TI  - Effects of training on the development of exercise-induced arterial hypoxemia in
      horses.
AB  - OBJECTIVES: To compare the development of exercise-induced arterial hypoxemia in
      horses before and after training, and to determine whether increases in maximum
      oxygen uptake (VO2max) following training results in a greater degree of exercise
      induced arterial hypoxemia. ANIMALS: 13 three- to five-year-old. Standardbred
      geldings without clinical signs of respiratory or cardiovascular disorders.
      PROCEDURE: Horses were rested for 4 months prior to commencing a 16-week training
      program. Arterial blood was collected from the transverse facial artery during
      standardized exercise tests performed before and after 8 and 16 weeks of
      training. Variables measured during exercise tests included arterial blood gas
      tensions and VO2max. Training and testing was performed on a treadmill set at a
      10% slope. RESULTS: Minimum arterial partial pressures of oxygen (PaO2) during
      exercise decreased from 83.3 +/- 1.5 mm of Hg before training to 77.8 +/- 1.0 mm
      of Hg after 16 weeks of training. Maximum arterial oxygen content increased from
      239.2 +/- 3.1 to 257.9 +/- 3.8 ml/L, which resulted from an increase in
      hemoglobin concentration. The VO2max increased by 19% following training. Minimum
      values of PaO2 and arterial oxygen saturation were significantly correlated with
      VO2max when data from each stage of training were pooled. Calculated values for
      minimum alveolar oxygen tension decreased after 8 weeks of training, and alveolar
      ventilation increased at the end of training. Alveolar-arterial oxygen tension of
      difference increased by 4 mm of Hg following training. CONCLUSIONS: In trained
      horses, an increase in VO2max is associated with a decrease in minimum PaO2,
      during intense exercise and is mostly attributable to an increase in the alveolar
      arterial oxygen tension difference. Therefore, interpretation of blood gas data
      from exercising horses should take into consideration VO2max.

PMID- 9185977
TI  - Effect of sodium bicarbonate administration on renal function of horses.
AB  - OBJECTIVE: To describe changes in renal function of horses after oral and i.v.
      administration of sodium bicarbonate (NaHCO3) and to determine whether changes
      are dose dependent. ANIMALS: 6 Standardbred mares. PROCEDURE: Blood and urine
      samples for determination of renal function were collected immediately before and
      at hourly intervals for 12 hours after administration of each of 3 oral doses
      (1,500, 1,000 and 250 mg/kg of body weight, in 3 L of water) and 1 i.v. dose (250
      mg/kg, 5% solution) of NaHCO3, or water (3 L orally). RESULTS: NaHCO3 induced
      increases in urine flow; electrolyte-free water reabsorption; urine
      concentrations of sodium and bicarbonate; fractional excretion of sodium,
      potassium, chloride, and bicarbonate; urinary excretion and clearance of sodium
      and bicarbonate; urine pH and anion gap; and mean plasma concentration of
      antidiuretic hormone. NaHCO3 induced attenuation in reduction with time of urine
      excretion and clearance of potassium, chloride, and osmoles, and induced
      reduction in urine osmolality. Plasma aldosterone and atrial natriuretic peptide
      concentrations and glomerular filtration rate were not modified. CONCLUSIONS:
      Renal responses to NaHCO3 load emphasize conservation of plasma volume and
      reestablishment of acid-base balance over control of hyperosmolality by diuresis,
      natriuresis, and increased bicarbonaturia. These responses imply a large fluid
      shift from the extravascular space to the vascular compartment, which was
      eliminated via diuresis, thus preventing hypervolemia.

PMID- 9185976
TI  - Effect of sodium bicarbonate administration on blood constituents of horses.
AB  - OBJECTIVE: To describe changes in blood constituents of horses after oral and
      i.v. administration of sodium bicarbonate (NaHCO3), and to determine whether the
      changes are dose dependent. ANIMALS: 6 adult Standardbred mares. PROCEDURE: 3
      oral doses (1,500, 1,000, and 250 mg/kg of body weight) or 1 intravenous dose
      (250 mg/kg, 5% solution) of NaHCO3 in 3 L of water, or water (3 L orally), were
      given to the mares; then changes in blood constituents were measured. Access to
      food and water was denied during the experiment. Blood samples were collected
      immediately before treatment and at hourly intervals for 12 hours after
      treatment, and were analyzed for blood gas tensions; serum osmolality; serum
      sodium, potassium, chloride, and creatinine concentrations; PCV; and total solids
      concentration in plasma. RESULTS: All NaHCO3 treatments induced significant (P <
      0.05) metabolic alkalosis, hypernatremia, hypokalemia, and hyperosmolality for at
      least 8 hours. In mares given the 1,500- and 1,000-mg doses of NaHCO3 orally,
      hypercapnia persisted for at least 12 hours, whereas hypercapnia lasted 2 hours
      in mares given the 250-mg dose orally or i.v. (P < 0.05). A tendency for
      reduction in PCV, proteins in plasma concentration, and serum concentration of
      chloride was observed 1 hour after i.v. administered doses of NaHCO3.
      CONCLUSIONS: Oral or i.v. administration of NaHCO3 (> or = 250 mg/kg) to resting
      horses without ad libitum access to water induces significant and persistent acid
      base and electrolyte changes.

PMID- 9185978
TI  - Muscarinic hyperresponsiveness of antigen-sensitized feline airway smooth muscle
      in vitro.
AB  - OBJECTIVE: To determine the effect of in vivo antigen sensitization (Ascaris
      suum) of cats on tracheal smooth muscle (TSM) and bronchial smooth muscle (BSM)
      muscarinic reactivity in vitro. ANIMALS: Healthy domestic shorthair cats of
      either sex. PROCEDURE: Cats were sensitized and were long-term antigen (or sham)
      challenge exposed for 6 weeks by aerosolization with soluble Ascaris suum.
      Tracheal and BSM preparations were obtained and stimulated in vitro by electrical
      field stimulation (EFS), acetylcholine (ACh, a muscarinic agonist), and
      physostigmine (an AChase inhibitor). Responses were compared with responses of
      comparable tissues from sham antigen challenge-exposed cats. RESULTS: Tracheal
      and BSM from sensitized, compared with sham-sensitized (control), cats had
      greater isometric contraction (expressed as percentage of the response observed
      for isotonic, 63 mM KCl-elicited contraction [% KCl]) in response to endogenous
      (EFS) and exogenous muscarinic receptor activation (ACh). Contractions in
      response to EFS by TSM from control cats were 74% KCl vs 97% KCl for antigen
      sensitized TSM (P < 0.04). Muscarinic responses were augmented comparably by in
      vivo sensitization; TSM from control cats contracted to 190% KCl vs 230% KCl (P <
      0.03) for TSM from immune-sensitized cats. Physostigmine augmented responses of
      all tissues to ACh so that TSM from control (290% KCl) and antigen-sensitized
      (257% KCl) cats were similar. Responses of BSM from antigen-sensitized cats had
      similar augmentation of contractile response to EFS and ACh. CONCLUSIONS: Long
      term in vivo antigen sensitization increases numbers of muscarinic receptors on
      airway smooth muscle or decreases the availability or activity of AChase in cats.
      CLINICAL RELEVANCE: Modulation of muscarinic receptors may be useful for
      treatment of asthmatic cats with in vivo airway hyperreactivity.

PMID- 9185979
TI  - Hematologic and systemic toxicoses associated with carboplatin administration in
      cats.
AB  - OBJECTIVE: To determine prevalence and severity of carboplatin-induced dose
      limiting toxicoses in the cat. ANIMALS: 9 healthy, 6- to 7-month-old cats
      weighing 4.7 (range, 3.0 to 6.5) kg. PROCEDURE: Cats were given a single i.v.
      bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3)
      mg/m2 of body surface area. RESULTS: Dose-limiting neutropenia and
      thrombocytopenia were significant in all cats given carboplatin at 200 or 250
      mg/m2. Weight loss, changes in appetite, and evidence of respiratory difficulty,
      as well as vomiting, diarrhea, or lethargy were not observed at any time during
      the 28-day period. At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/-
      303 neutrophils/microliters) was observed on day 17 and the platelet count nadir
      (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after
      carboplatin administration. CONCLUSIONS: Carboplatin appears to be safe and
      clinically well-tolerated when given i.v. as a single bolus at a dosage of 200
      mg/m2 to clinically normal cats. The dose-limiting toxicity of a single i.v.
      administered bolus is neutropenia. The nadir of a 200 mg/m2 i.v. administered
      dose occurs on day 17 (1,110 +/- 165 neutrophils/microliters) and neutropenia (<
      2,000 neutrophils/microliters) lasts from day 14 through day 25 after carboplatin
      administration. CLINICAL RELEVANCE: The fatal dose-related pulmonary toxicosis
      observed in cisplatin-treated cats was inapparent in carboplatin-treated cats. To
      adequately determine the therapeutic role of carboplatin in tumor-bearing cats, a
      moderately tolerated dose of carboplatin of 200 mg/m2 given i.v. once every 4
      weeks should be considered.

PMID- 9185980
TI  - Apoptotic condensations in M-phase cells.
AB  - BACKGROUND: Apoptosis is a morphologically distinctive form of programmed cell
      death/cell suicide in which genomic DNA degradation/fragmentation and variegated
      dense chromatin aggregates are characteristic hallmarks that have never been
      demonstrated in mitotic cells. Perceptions of mutual exclusivity between
      apoptosis and mitosis imply that M-phase cells cannot be apoptotic. However, in
      the present study we show apoptotic morphologies in M-phase cells after an acute
      oxidative stress and endonuclease digestion. METHODS: Degradation of genomic DNA
      in human Chang liver cells (American Type Culture Collection, ATCC CCL13) was
      demonstrated by flow cytometric cell-by-cell evaluation of (a) propidium iodide
      intercalative binding to DNA and (b) terminal deoxynucleotidyl transferase (TdT)
      mediated 3'OH nick end labeling (TUNEL) of fragmented DNA. Oxidative stress was
      imposed by a 30-min prepulse with 200 microM vanadyl(4), which produces hydroxyl
      free radicals (OH*), the most reactive of the free radical species. Oxidative
      stress in the cells was demonstrated by evaluating glutathione-S-transferase
      (GST)-mediated monochlorobimane-glutathione adduct fluorescence for glutathione
      content, the main reducing agent of a cell, and methylene blue redox
      metachromasia, which is a deep color when oxidized and colorless when reduced.
      Cells with DNA fragmentation were highlighted by TUNEL. Apoptotic morphologies
      were visualized by staining with Giemsa and neutral red dyes and by DNA-propidium
      iodide binding to chromatin. Direct endonuclease induction of apoptotic
      morphologies in permeabilized M-phase cells was produced by 1 hr incubation (37
      degrees C) with 16 units/ml of micrococcal nuclease. RESULTS: The genomic DNA of
      proliferative cells, namely in G2/M phase of the cell cycle, was degraded by
      vanadyl(4) prepulsing and by micrococcal nuclease digestion, concomitantly with
      DNA fragmentation shown by TUNEL. Cytological profiles showed GSH depletion and M
      phase cells with particularly high oxidative reactivity indicated by methylene
      blue redox metachromasia. DNA fragmentation in M-phase cells was highlighted by
      TUNEL. Characteristic apoptotic condensations, ranging from single-ball
      condensations to "pulverized" aggregates of a mitotic catastrophe, buddings, and
      "apoptotic bodies," were found in prophase, metaphase, anaphase, and telophase
      mitotic cells. The observed separation of condensed chromatin aggregates from the
      main chromosome mass in prophase and metaphase cells could explain micronuclei,
      linking it with apoptosis. Direct endonuclease digestion readily produced
      apoptotic morphologies in interphase and in M-phase cells. CONCLUSION: Apoptotic
      morphologies in M-phase cells can be induced indirectly via oxidative stress or
      directly via endonuclease activity, which has long been established as a
      pervading hallmark of apoptosis.

PMID- 9185981
TI  - Cellular and subcellular distribution of 7B2 in porcine Merkel cells.
AB  - BACKGROUND: Merkel cells are neuroendocrine cells located in the skin and oral
      mucosa of various mammalian species. These cells express multiple peptides as
      well as serotonin. Although the precise function of Merkel cells is still
      unknown, different studies support its role as mechano-electric transducer. 7B2
      granin (secretogranin V) is a polypeptide isolated from the pituitary gland and
      present in the dense-cored granules of neuronal and paraneuronal cells. METHODS:
      The expression of the 7B2 in Merkel cells of pig snout skin was analysed by
      immunohistochemical techniques. The streptavidin-biotin peroxidase complex
      procedure was employed for light microscopy. A postembedding method using
      immunoglobulin-colloidal gold complexes was employed for the ultrastructural
      studies. RESULTS: Immunoreactivity for 7B2 was observed in virtually all Merkel
      cells, both in epidermis and vibrissae. The immunostaining was shown in the basal
      side of cytoplasms where neuroendocrine granules were accumulated. Immunoelectron
      microscopy allowed us to demonstrate that 7B2 labelling was located on the
      electrondense granules. Nuclei and epidermal nerve terminals associated with
      merkel cells did not show immunoreactivity. CONCLUSIONS: The polypeptide 7B2 is
      present in the dense-cored granules of Merkel cells. This result is consistent
      with the possible role for 7B2 in secretory granules' processing. To our
      knowledge this is the first evidence of 7B2 protein in Merkel cells.

PMID- 9185982
TI  - Ultrastructure of the unusual accessory submandibular gland in the fringe-lipped
      bat, Trachops cirrhosus.
AB  - BACKGROUND: The phyllostomid fringe-lipped bat, Trachops cirrhosus, is sui
      generis (in a family of ca. 138 species) in that it subsists in part on tropical
      frogs. These amphibians frequently possess highly toxic integument. We examined
      the salivary glands of this bat to determine if these glands could be the source
      of protective factors that permit consumption of seemingly unsavory prey. The
      parotid and principal salivary glands of this bat are similar to homologous
      glands in other phyllostomids, but the accessory submandibular gland is unique.
      METHODS: The accessory submandibular glands of live-trapped T. cirrhosus were
      fixed and processed for transmission electron microscopy by conventional means.
      RESULTS: The accessory submandibular gland consists of follicles and ducts. The
      principal cells of the follicular walls have an abundance of rough endoplasmic
      reticulum (RER), free ribosomes, and extensive Golgi apparatuses. Typically,
      these cells have relatively few serous secretory granules. The ells contain
      collections of peculiar lipid droplets, and some of their mitochondria have dense
      crystalloids within expanded cristae. A layer of irregular, moderately dense
      bodies lies immediately subjacent to the luminal plasmalemma; it is not clear if
      these structures are endocytotic or exocytotic. Clusters of mucous cells, some of
      which have a single, hugely distended RER cisterna, are ensconced in the
      follicular walls; mucus from these cells reaches the lumen via intercellular
      canaliculi. Ducts progress from simple cuboidal to simple columnar epithelium.
      They lack basal striations, and their constituent cells contain relatively few
      mitochondria. Follicles and ducts have numerous myoepithelial cells at their
      periphery, and both are heavily innervated by hypolemmal nerve terminals.
      CONCLUSIONS: The unusual accessory submandibular gland in T. cirrhosus documents
      the extreme modifications in gland histology and in cell ultrastructure that have
      occurred in mammalian families. The cells composing the follicle walls and ducts
      bear little similarity to typical acinar or duct cells. Duplication of the
      submandibular gland in some bat lineages might be the key innovation underlying
      such plasticity. The heavy innervation of both follicles and ducts also implies
      that these structures are sensitive to and capable of responding to various
      inputs, perhaps including dietary factors.

PMID- 9185983
TI  - Ultrastructure of the parotid salivary glands in seven species of fruit bats in
      the genus Artibeus.
AB  - BACKGROUND: In previous studies, we determined that the submandibular glands of
      five species of Neotropical fruit bats in the genus Artibeus had seromucous
      granules in their demilune cells with substructures that varied interspecifically
      in accordance with systematic relationships. Moreover, the striated ducts in
      these frugivores exhibited structural modifications that apparently are related
      to the consumption of a diet rich in potassium, but deficient in sodium. We now
      turn our attention to the parotid gland in a large number of species in this
      genus to determine if it follows the same structural pattern as does the
      submandibular gland. METHODS: Members of seven different species of Artibeus were
      live-trapped in various Neotropical locations. The parotid glands were extirpated
      from euthanized bats, fixed in the field, and prepared for electron microscopic
      examination by conventional means. The parotid glands in all seven species were
      virtually identical in morphology. The acinar cells (determined to be seromucous
      on the basis of ultrastructural criteria) contain large numbers of what appear to
      be vacuoles, but which are a type of secretory granule. These granules have an
      electron-lucent matrix and may contain one or several circular membranous
      profiles arranged either concentrically or in a random array. These granules
      appear to form by progressive dilatation of the termini of Golgi saccules, with
      the nascent granules finally severing their connection with the Golgi apparatus.
      Many of the internal membranous profiles are formed simply by invaginations of
      the limiting membrane of the granule; others may result from indentation of the
      limiting membrane by protrusions from adjacent granules; the source of multiple
      internal membranes in certain granules is unclear. The exocytosis of these
      granules results in the acinar and intercalated duct lumina being filled with an
      abundance of membranous material. Such extruded membranes are present in some
      striated ducts, but not in others, suggesting that they are degraded during
      passage through the duct system. The striated ducts are of conventional
      appearance, lacking the frondose processes that are prominent in the
      submandibular glands of Artibeus. CONCLUSIONS: The parotid gland in Artibeus
      shows none of the interspecific ultrastructural variability that characterizes
      the submandibular gland in bats of this genus. The seromucous acinar cells
      secrete granules that release phospholipids as well as glycoconjugates into the
      saliva. Based on the lack of frondose processes with their sodium-transporting
      portasomes, the striated ducts of the parotid gland are less concerned with
      electrolyte homeostasis than are those in the submandibular gland.

PMID- 9185984
TI  - Thickness distribution of the subchondral mineralization zone of the trochlear
      notch and its correlation with the cartilage thickness: an expression of
      functional adaptation to mechanical stress acting on the humeroulnar joint?
AB  - BACKGROUND: The thickness of cortical bone and the density of cancellous bone
      have been shown to reflect local mechanical stress. However, little is known
      whether this also applies to the thickness of the subchondral mineralization zone
      (SMZ). Since the humeroulnar joint may be regarded as a model of bicentric load
      transmission, we examined the thickness distribution of the SMZ of the trochlear
      notch. METHODS: Fourteen trochlear notches were examined. Eight joint surfaces of
      these ulnae were completely divided, 4 incompletely subdivided, and 2 remained
      undivided. After embedding, sagittal sections were prepared. The thickness
      distributions of SMZ and cartilage were measured, graphically reconstructed, and
      the correlation between the two calculated for each joint. RESULTS: The thickness
      of the SMZ lies between 120 and 1,400 microns. Regular patterns were observed
      with ventral and dorsal maxima, with close correlations between the type of joint
      and the thickness distribution of the SMZ. The cartilage thickness varied between
      350 and 2,000 microns. The pattern of cartilage thickness differed significantly
      from that of the SMZ. The mean correlation coefficient between SMZ and cartilage
      thickness was 0.3. CONCLUSIONS: The SMZ thickness depends upon the type of joint
      and appears to be an expression of the local loading history of the SMZ. The
      bicentric transmission of force at the humeroulnar joint is reflected in the
      bicentric distribution of SMZ thickness. A possible explanation for the different
      distributions of SMZ and cartilage could be the differing types of local
      mechanical stress acting on bone and cartilage, and/or the different reactions of
      osteocytes and chondrocytes.

PMID- 9185985
TI  - Tibial segmental defect repair: chondrogenesis and biomechanical strength
      modulated by basic fibroblast growth factor.
AB  - BACKGROUND: The effect of recombinant human basic fibroblast growth factor (bFGF)
      on cartilage development and bone biomechanical strength during healing of a
      tibial segmental defect was studied in the rat. Two reports on the effect of
      basic FGF administration during fracture healing and several reports on the
      effects of acidic FGF have documented different responses of callus cartilage to
      this important growth factor. This is the first report of the effect of bFGF on
      cartilage formation in the healing of a grafted segmental defect in the rat.
      METHODS: The tibiae of 80 male rats underwent segmental resection of the mid
      diaphyseal region. One-half of this group consisted of controls that received
      insertion of an intramedullary wire with a coralline hydroxyapatite graft and
      Gelfoam without bFGF. The tibiae of the other half were treated identically but
      had the Gelfoam impregnated with 1 microgram bFGF. Animals were killed at 2, 4,
      and 8 weeks postoperatively. Histological sections were stained with toluidine
      blue to differentiate the cartilage. Areas of metachromatically stained
      extracellular matrix, cell areas, cell size, and cellularity were quantified by
      using image analysis. Unfixed treated and control tibiae were tested for bone
      failure strength by using four-point bending on an Instron machine. RESULTS:
      Control bone failure strength was significantly greater than bFGF-treated bones
      at 2 weeks and energy-to-failure was significantly decreased in treated bones at
      2 weeks. Although strength increased with time in all groups, treated groups at 4
      and 8 weeks did not differ from controls. Basic FGF treatment promoted an
      increase in the development of normal hyaline cartilage and vasculogenesis at 2
      weeks as compared with controls. Total cartilage declined over time in all
      groups. Average cell size and cell number did not change with either treatment or
      time. Bone formation and healing was equivalent in treated and control groups at
      8 weeks. CONCLUSIONS: The results indicate that bFGF released directly and
      initially but not continuously exerts a transient positive effect on hyaline
      cartilage formation at the expense of repair site strength and does not
      accelerate healing.

PMID- 9185986
TI  - Stereological analysis of bone architecture in the pig zygomatic arch.
AB  - BACKGROUND: Stereological analysis of trabecular bone structure may reveal
      information about regional variations in stress distribution, especially in areas
      like the zygomatic arch in which those variations are difficult to assess
      mechanically. This study investigates regional differences in trabecular
      orientation, thickness, and density in the zygomatic and squamosal bones of pigs.
      METHODS: Zygomatic arches were serially sectioned frontally (n = 4), horizontally
      (n = 4), or parasagittally (n = 4), at a thickness of 0.8 mm. Sections were
      viewed under a stereomicroscope; video-images were digitized and analyzed with an
      automated program. RESULTS: All regions were anisotropic. Predominant orientation
      of trabeculae differed between and within bones. Three main patterns were seen.
      Anteriorly, zygomatic trabeculae were mainly arranged vertically and
      anteroposteriorly (relative to the occlusal plane). Posteriorly, including the
      jaw joint region, the squamosal featured primarily mediolateral trabeculae. In
      the midsection of the arch, where the two bones overlap, the trabeculae displayed
      a predominantly anteroposterior orientation with a secondary mediolateral peak.
      Trabeculae were typically 0.3-0.4 mm wide and occupied 40-50% of the area of the
      sections with few regional variations. CONCLUSIONS: Trabecular bone in the pig
      zygomatic arch is arranged orthogonally, relative to the occlusal plane. In
      conjunction with information from strain gauge recording, these data suggest that
      the zygomatic bone is bent in the parasagittal plane whereas the squamosal is
      bent out-of-plane. The mediolateral trabeculae in the posterior regions are
      consistent with a cantilever effect at the jaw joint.

PMID- 9185987
TI  - Ultra-high-resolution scanning electron microscopy of mitochondria and
      sarcoplasmic reticulum arrangement in human red, white, and intermediate muscle
      fibers.
AB  - BACKGROUND: Human skeletal muscle fibers are the red, white, and intermediate
      fibers. They differ in their mitochondrial structure and enzyme activity.
      Scanning electron microscopy (SEM) was used on specially prepared specimens to
      determine the distinctive features of mitochondria and sarcoplasmic reticulum
      (SR) in each fiber type. METHODS: Specimens of human limb muscles were
      glutaraldehyde fixed, frozen, fractured, and macerated by the aldehyde-osmium
      DMSO-osmium procedure to expose large areas of mitochondria and SR. Osmium
      hydrazine-impregnated tissues were examined without metal coating by ultra-high
      resolution SEM. RESULTS: In white fibers, paired long, thin mitochondria
      encircled myofibrils at the I-band level. In red fibers, the paired rows of
      stubby mitochondria at the I-band level were often connected across the A-band to
      the next row of mitochondria by a slender mitochondrial stalk. Intermediate fiber
      mitochondria resembled those in red fibers but were longer and thinner.
      Intermyofibrillar mitochondrial columns were most common in red fibers. All three
      muscle types had T-tubules along the A-I junction level, and small periodic
      terminal cisternae formed triads or dyads. Sarcotubules from terminal cisternae
      formed continuous three-dimensional networks at the I-band level, but
      intermittent straight sarcotubules, narrow two-dimensional networks, and some
      axial tubules traversed the A-band. The subsarcolemmal space had continuous two
      dimensional SR at the H-band level and a coarse SR network at the I-band. These
      two SR networks were connected by single A-band sarcotubules. CONCLUSIONS:
      Mitochondrial shape and configuration were distinctive for each human skeletal
      muscle fiber type, but the SR was similar in all muscles examined.

PMID- 9185988
TI  - Anatomy and development of the sinoatrial valves in the dogfish (Scyliorhinus
      canicula).
AB  - BACKGROUND: We describe the adult anatomy and the development of the cardiac
      sinoatrial valves in the dogfish (Scyliorhinus canicula). METHODS: We use
      scanning electron microscopy, histological and histochemical techniques in 39
      hearts from embryos and adult specimens. RESULTS: The sinoatrial valvular set of
      the adult dogfish is composed of two transverse valves laterally attached to the
      sinoatrial junction at their bases. Both valves are composed of two muscular
      layers, the sinusal and the atrial, whose histological features are similar to
      the cardiac wall which they face. Collagen bundles, elastic fibers and
      fibroblasts are present between the muscular layers. The extracellular matrix
      between the valvular layers also contains sulphated and non-sulphated
      glycosaminoglycans. The sinoatrial valves develop from two lateral infoldings of
      the cardiac wall. The left fold is deeper than the right, causing a shift of the
      sinoatrial communication to the right. The epicardium progressively covers the
      outer sinoatrial groove and the space between the folds becomes populated by
      mesenchymal cells. The posterior atrioventricular endocardial cushion is in
      contact with the base of the left fold until the embryo has about 40 mm TL.
      CONCLUSIONS: The sinoatrial valves, in the dogfish, develop from lateral
      infoldings of the cardiac wall. This origin results in histological and
      histochemical differences between the two muscular layers which constitute the
      valves of the adult. The comparison of the sinoatrial valve morphogenesis between
      the dogfish and some higher vertebrates suggests that the right sinoatrial valve,
      but not the left, is homologous throughout the vertebrate phylogeny.

PMID- 9185989
TI  - Ultrastructural changes of the myocardium in the embryonic rat heart.
AB  - BACKGROUND: Ultrastructural changes of the embryonic heart have been described,
      and quantitative studies have reported the changes of cellular organelles in late
      fetal and postnatal development. However, no specific data are available on the
      quantitative morphology of the individual segments and intersegmental junctions
      of the early embryonic heart, although these components must have different
      functions. METHODS: We measured the absolute volumes of glycogen, Golgi complex,
      myofibrils, mitochondria, and the surface areas of the rough endoplasmic
      reticulum and mitochondrial cristae in the different regions of the embryonic rat
      heart by using stereological tools. RESULTS: During embryonic development, the
      cardiac segments and intersegmental junctions increase their glycogen volume. The
      sinoatrial junction and primary fold show a more rapid increase than all the
      other cardiac regions, whereas the atrioventricular canal shows a high level of
      glycogen content throughout the period studied. The Golgi complex and rough
      endoplasmic reticulum show a conspicuous decrease from day 15 onward. The
      cellular content of myofibrils and mitochondria and the surface area of the
      mitochondrial cristae show a gradual increase from day 11 to day 17 of
      development, but full maturation apparently takes place in late fetal and early
      postnatal stages. At day 15 of development, the cellular volumes of myofibrils
      and mitochondria show a temporary decrease. CONCLUSIONS: The glycogen content
      cannot be explained on the basis of metabolism alone. The storage of glycogen is
      hypothesized to serve mechanical cell stability and may also be related to a
      target mechanism for ingrowing nerves. Myofibrillar and mitochondrial contents of
      the myocytes indicate a relatively late differentiation of the venous pole of the
      heart. Uninterrupted maturation is only started at the time of septation.

PMID- 9185990
TI  - Stereological study of stage 34 chicken hearts with looping disturbances after
      retinoic acid treatment: disturbed growth of myocardium and atrioventricular
      cushion tissue.
AB  - BACKGROUND: In a previous study retinoic acid treatment of chicken hearts has
      resulted in a spectrum of looping disturbances. Because of a decrease in
      contraction force of these hearts, the myocardial volume was hypothesized to be
      altered. Because retinoic acid has been suggested to influence endocardial
      cushion volumes, these were estimated as well. METHODS: The previously studied
      hearts were used for estimating the absolute volumes of the atrial and
      ventricular myocardium and of the endocardial cushions by means of Cavalieri's
      principle. To measure the surface density of the trabeculations according to the
      isector method, we used retinoic acid treated hearts, which were perfusion fixed
      and in which the sections were isotropic uniform random. The volumes and surface
      densities found in the three morphologically distinguished groups, i.e., intact
      septum, isolated ventricular septal defect and double outlet right ventricle,
      were compared with those in shams. RESULTS: A significant volume decrease was
      found in the right ventricular free wall myocardium of the double outlet right
      ventricle. No significant differences were found in the surface densities of the
      trabeculae. The volume of the atrioventricular cushion tissue in the double
      outlet right ventricle hearts was significantly increased. The morphological
      spectrum observed previously was also expressed in the right ventricular
      myocardial volume, which appeared to decrease from the least to the most
      malformed hearts, and in the volume of the atrioventricular cushion tissue, which
      appeared to increase. CONCLUSIONS: Several studies have shown pathology in
      myocardial and cushion tissue after retinoic acid treatment. In this study we
      have found a decreased growth of the right ventricular myocardium and an
      increased growth of the atrioventricular cushion tissue. We suggest that the
      previously found looping disturbance causes changed hemodynamics, as reported
      elsewhere, and that these result in changes in growth. We cannot exclude a direct
      effect of retinoic acid on the myocardium, which has to explain the looping
      disturbance.

PMID- 9185991
TI  - Some morphological changes in the rat thyroid gland during experimental
      hyperphenylalaninemia.
AB  - BACKGROUND: Little is known about the effect of phenylketonuria on the thyroid
      gland. In the present study, this problem was investigated by using a defined
      experimental model of hyperphenylalaninemia (HPA). METHODS: The experimental
      group was subjected to an HPA regimen (Matsuo and Hommes, 1988. Neurochem. Res.,
      13:867-870) from the 5th day of postnatal development. The pups were decapitated
      on the 7th, 14th, 21st, 28th, and 35th days. The thyroid glands were fixed in
      Bouin's fluid and routinely embedded in paraffin. The staining techniques used
      were Mallory-Slinchenko's method, toluidin blue, silver impregnation of the
      basement membrane, immunohistochemical staining of the proliferating cell nuclear
      antigen (PCNA), and neuron-specific enolase (NSE). RESULTS: The size of the
      follicles was less than that in the control group. There were no substantial
      changes in the epitheliomer structures. In almost all of the treated groups, a
      reduction in the number of PCNA+, NSE+, and mast cells was observed until the
      28th day. On the 28th day of HPA, the level of mast cell degranulation was higher
      (61%) than that in the control group. On the 35th day, these parameters began to
      reach normal levels. From the 28th day, degenerative changes in the thyroid
      glands of treated animals were observed in the NSE+ cells. CONCLUSIONS: The HPA
      condition mainly has an influence on the number and structure of the NSE+ cells
      of the thyroid gland. One may assume that under HPA the increase in mast cell
      degranulation plays a significant role in the normalisation of the parameter of
      the thyroid gland.

PMID- 9185992
TI  - Development of the human knee joint ligaments.
AB  - BACKGROUND: Many studies have been published on the development of the human knee
      joint, but scant attention has been given to the development of the knee joint
      ligaments. The only elements that have received much attention are the cruciate
      ligaments and their relationships with the synovial membrane. METHODS: We
      summarize our observations on the development of the knee joint ligaments in 50
      serially sectioned human embryonic and fetal lower limbs (26 embryos and 24
      fetuses). RESULTS: The patellar ligament begins to form in O'Rahilly stage 20,
      with the muscle fibers of the quadriceps muscle being attached inferiorly to the
      tibial tuberosity. The cruciate ligaments (beginning with the posterior) arise
      from the articular interzone in O'Rahilly stage 21. Subsequently, with the
      organization of the Wrisberg's meniscofemoral ligament, in week 10 of
      development, the cruciate ligament system is completed. The lateral collateral
      ligament begins to form in O'Rahilly stage 23, and from its first appearance it
      is independent of the knee joint capsule. At this time, development of the tendon
      of the popliteus muscle begins. The medial collateral ligament begins to develop
      in week 9 of development as a condensation of the joint capsule. Two weeks later,
      the intra-articular pad of fat begins to form from mesenchymal tissue below the
      patella and between the cruciate and the patellar ligaments. With the
      organization of the suprapatellar bursa in week 14 of development, knee joint
      development is complete. CONCLUSIONS: The morphogenetic time table of the knee
      joint ligaments was established.

PMID- 9185993
TI  - Development of the human knee joint.
AB  - BACKGROUND: Many studies have been published on the development of the human knee
      joint, but different investigators disagree on its morphogenetic time table. Most
      discrepancies center on the cavitation of the knee joint and the participation of
      the superior tibiofibular joint in the joint knee system. METHODS: We summarize
      our observations of the development of the knee joint in 50 serially sectioned
      human embryonic and fetal lower limbs (26 embryos and 24 fetuses). RESULTS: The
      epiphysis of the femur and tibia become condryfied from O'Rahilly stage 18, and
      ossification begins during the 13th week of development. The patella appears as a
      dense blastema during O'Rahilly stage 19, becomes condryfied during O'Rahilly
      stage 22, and begins its ossification during the 14th week of development. The
      knee joint cavity appears during O'Rahilly stage 22, initially as the
      femoropatellar joint. This process begins at the periphery of the articular
      interzone. The superior tibiofibular joint communicates with the lateral
      meniscotibial joint between 10 and 11 weeks of development and becomes separated
      from the 13 week on. The menisci arise from the eccentric portions of the
      articular interzone during O'Rahilly stage 22; however, until week 9 of
      development, they are not easily distinguishable. CONCLUSIONS: We establish the
      morphogenetic time table of the human knee joint.

PMID- 9185994
TI  - Expression patterns of connexin43 protein during facial development in the chick
      embryo: associates with outgrowth, attachment, and closure of the midfacial
      primordia.
AB  - BACKGROUND: In a prior report, evidence was presented for the presence of gap
      junction proteins [connexin32 and connexin43 (Cx43)] in embryonic facial
      primordia. The purpose of the present study was, first, to examine in detail the
      patterns of distribution of Cx43 protein in embryonic chick facial primordia and,
      second, to consider the possible roles played by this protein during midfacial
      development. METHODS: Chick embryo heads were serially sectioned and processed
      for immunofluorescent localization of Cx43. The developmental stages examined
      encompassed the period of formation, enlargement, and union of the facial
      primordia. Western blot analysis of the facial primordia was also performed.
      RESULTS: Analysis of serial sections revealed the presence of signal in both
      epithelium and mesenchyme at sites of attachment in each of the midfacial
      primordia (i.e., the medial nasal, lateral nasal, and maxillary processes).
      Furthermore, although signal was concentrated in mesenchyme in the distal tips of
      the primordia at sites of attachment, immunoreactivity was absent, sparse, or
      less intense outside the areas of attachment. In some cases (i.e., the maxillary
      process), immunoreactive signal in mesenchyme did not appear in the distal tip
      until the primordia approximated each other or contact of the primordia was
      initiated. Most significantly, signal was also found between the facial primordia
      in nonprimordial epithelium and mesenchyme at sites where the primordia were
      joined. CONCLUSIONS: These data suggest that the expression of Cx43 protein is
      spatially and temporally regulated in the facial primordia and that the patterns
      of expression that were observed are significant to the cascade of events that
      ultimately lead to the attachment and union of the primordia that form the
      midface.

PMID- 9185995
TI  - Sympathetic efferent pathways projecting bilaterally to the vas deferens in the
      rat.
AB  - BACKGROUND: The laterality of the signals passing through the splanchnic nerves
      to the vas deferens has not been well studied. METHODS: The present study was
      designed to determine the bilateral distribution of sympathetic nerves to the rat
      vasa deferentia by measuring intravasal pressure (VP) responses to electrical
      stimulation of left lumbar splanchnic nerves (LSN) following consecutive
      transections of more distal nerves. RESULTS: L2-L6 LSN stimulation increased VP
      bilaterally. Left VP responses decreased slightly (< 20%) after section of the
      right hypogastric nerve (HGN) and then were abolished by subsequent section of
      branches (B-M-APG) between the left major pelvic (MPG) and accessory pelvic
      ganglia (APG). Left VP responses were decreased by > 80% after section of left
      HGN, not changed further by subsequent section of commissural branches (CB-MPG)
      between the MPG, and completely eliminated by section of commissural branches
      between the APG (CB-APG). Right VP responses were decreased slightly (< 20%) by
      section of the left HGN and then abolished by section of the right B-M-APG. These
      responses were also decreased by > 70% by section of right HGN, not changed by
      section of CB-MPG, but then completely eliminated by section of CB-APG.
      CONCLUSIONS: These results indicate that the left lumbar sympathetic pathway to
      the vas deferens is distributed bilaterally and exhibits two crossing points at
      the level of the inferior mesenteric ganglion and APG.

PMID- 9185996
TI  - Bcl-x expression influences keratinocyte cell survival but not terminal
      differentiation.
AB  - The epidermis is characterized by the continual turnover of its basic cellular
      unit, the keratinocyte. To determine whether genes known to regulate apoptosis
      could affect keratinocyte biology, transgenic mice overexpressing bcl-xL or bcl
      xS under the control of the human keratin 14 promoter were generated. The
      maturation process and cellularity of the stratified epidermis were not
      compromised in the transgenic mice. Transgene function was demonstrated by
      enhanced cell survival of bcl-xL transgenic versus wild-type primary keratinocyte
      cultures treated with etoposide. To test the response of these mice to genotoxic
      damage, wild-type and transgenic mice were irradiated with UV light. The bcl-xL
      transgenic mice showed a dramatically increased resistance to irradiation,
      whereas the bcl-xS transgenic mice showed an increased sensitivity to
      irradiation. In contrast, neither transgene influenced the rate of would repair.
      Interestingly, endogenous Bcl-x was rapidly induced in keratinocytes adjacent to
      the would. Taken together, these findings demonstrate that although the terminal
      differentiation program is not altered by Bcl-x, acute stress responses within
      the skin can be influenced by regulators of apoptosis such as Bcl-x.

PMID- 9185997
TI  - All-trans-retinoic acid mediates G1 arrest but not apoptosis of normal human
      mammary epithelial cells.
AB  - Retinoids mediate the normal growth of a variety of epithelial cells and may play
      an important role in the chemoprevention of certain malignancies. Loss of
      retinoic acid (RA) receptor-beta function may be an important event in mammary
      carcinogenesis, because the majority of breast cancers, in contrast to normal
      mammary epithelial cells, fail to express this receptor. We previously reported
      that all-trans-RA mediates G1 arrest as well as apoptosis in certain RAR beta
      transduced breast cancer cell lines. We now report the effect of RA on normal
      human mammary epithelial cells (HMECs), which express functionally active
      retinoid receptors. We observe that RA induces growth suppression and G1 arrest
      of these HMECs but find no evidence that RA mediates apoptosis in these normal
      cell strains. This RA-induced G1 arrest is temporally associated with decreased
      levels of hyperphosphorylated retinoblastoma protein without any significant
      changes in c-myc, p53, p21, or p27 expression. Expression of cyclin D1, cyclin
      dependent kinase 4, and cyclin E proteins, however, decreased in association with
      RA-mediated G1 arrest. Our studies suggest that growth inhibition, rather than
      apoptosis, may be a mechanism by which RA and RA receptors act to prevent the
      malignant transformation of normal mammary epithelial cells. The molecular
      target(s) of the activated RA receptors that mediate this G1 arrest in HMECs
      appear to be associated with a retinoblastoma-dependent pathway.

PMID- 9185998
TI  - Interleukin 1 beta converting enzyme-like proteases are essential for p53
      mediated transcriptionally dependent apoptosis.
AB  - p53-mediated apoptosis in baby rat kidney (BRK) cell lines transformed by E1A and
      p53(val135) requires a transcriptionally functional p53. Coexpression of the E1B
      19K protein in BRK cell lines transformed by E1A and p53(val135) rescues cells
      from p53-mediated apoptosis, and this is paralleled by the absence of both lamin
      and poly(ADP-ribose) polymerase cleavage. Therefore, the role of interleukin 1
      beta converting enzyme (ICE)-like porteases in p53-mediated, transcriptionally
      dependent apoptosis was investigated. The ICE-like protease CPP32 was
      proteolytically activated during p53-mediated apoptosis in BRK cells, and this
      required a transcriptionally competent p53. Substitution of the p53
      transactivation domain with the transactivation domain of herpes simplex virus
      VP16 (VP16/p53) resulted in accelerated kinetics of both apoptosis and Bax
      induction. Moreover, apoptosis induced by p53, VP16/p53, and Bax was abrogated by
      Z-VAD.FMK, an inhibitor of ICE-like proteases. These results indicate that all
      apoptotic pathways downstream of p53-mediated transcription converge upon the
      activation of ICE-like proteases.

PMID- 9186000
TI  - Oncostatin M-specific receptor mediates inhibition of breast cancer cell growth
      and down-regulation of the c-myc proto-oncogene.
AB  - Human oncostatin M (OM) is a M(r) 28,000 glycoprotein that has been shown to
      regulate cell proliferation and differentiation. The biological activities of OM
      can be mediated by two different heterodimeric receptor complexes, the leukemia
      inhibitory factor (LIF)/OM shared receptor and the OM-specific receptor. In this
      study, we have examined the growth-regulatory effect of OM on 10 breast cancer
      cell lines derived from human tumors. The cellular proliferation of seven of
      these breast cancer cell lines was inhibited by OM. The three cell lines that did
      not respond to OM treatment lacked the expression of OM receptors. The growth
      inhibitory activity of OM is examined further in the H3922 breast cancer cell
      line, which expresses the high-affinity OM receptor at a relatively higher level.
      We found that the cellular proliferation of H3922 cells was induced strongly by
      extrogenous epidermal growth factor (EGF), EGF-like factor, and basic fibroblast
      growth factor. The proliferative activities of these growth factors can be
      abolished totally by cotreatment of H3922 cells with OM. Treatment of H3922 cells
      with OM for 24 h did not block EGF binding or the induction of EGF receptor
      tyrosine phosphorylation. This finding suggests that OM interferes with the
      mitogenic signal at steps distal to the EGF receptor. Examination of proto
      oncogene expression demonstrated that OM down-regulates the c-myc gene in H3922
      cells. The biological effects reported herein are not shared by the OM-related
      cytokines interleukin 6 or LIF, as demonstrated by the inability of these
      proteins to inhibit cell growth or modulate c-myc gene expression in breast
      cancer cells. Additionally, the high-affinity binding of labeled OM cannot be
      displaced by LIF. Together, these data suggest that OM is a growth inhibitor for
      breast cancer cells. The inhibitory activity is mediated predominantly through
      the OM-specific receptor, and activation of this receptor abrogates growth factor
      stimulation and down-regulates the c-myc proto-oncogene.

PMID- 9185999
TI  - The ETS1 transcription factor is expressed during epithelial-mesenchymal
      transitions in the chick embryo and is activated in scatter factor-stimulated
      MDCK epithelial cells.
AB  - In embryos and in human tumors, the expression of the ETS1 transcription factor
      correlates with the occurrence of invasive processes. Although this was
      demonstrated in cells of mesodermal origin, the expression of ETS1 was not
      detected in epithelial cells. In the present study, we show that during early
      organogenesis in the chick embryo, ETS1 mRNA expression was transiently induced
      in epithelial structures, during emigration of neural crest cells and dispersion
      of somites into the mesenchymal sclerotome. In contrast, the expression of ETS1
      was not detected in situations where epithelial layers stayed cohesive while
      forming a new structure, such as the dermomyotome forming the myotome. The
      involvement of ETS1 in epithelial cell dissociation was examined in MDCK
      epithelial cells stimulated by scatter factor/hepatocyte growth factor (SF/HGF),
      a potent inducer of cell dissociation and motility. SF/HGF was found to stimulate
      ETS1 mRNA and protein expressions, and these increases coincided with the
      dispersion of cells and the expression of protease mRNAs, such as urokinase-type
      plasminogen activator and collagenase, but not with the protease inhibitor,
      plasminogen activator inhibitor type 1. Furthermore, we showed that SF/HGF was
      able to induce a transcriptional response involving ETS1 by using artificial as
      well as cellular promoters, such as the urokinase-type plasminogen activator and
      collagenase 1 promoters, containing RAS-responsive elements with essential ETS
      binding sites. These data demonstrate expression of ETS1 during epithelial
      mesenchymal transitions in the developing embryo and show that ETS1 can act as a
      downstream effector of SF/HGF in MDCK epithelial cells. Taken together, these
      data identify ETS1 as a molecular actor of epithelia cell dissociation.

PMID- 9186001
TI  - Tissue-specific expression of human achaete-scute homologue-1 in neuroendocrine
      tumors: transcriptional regulation by dual inhibitory regions.
AB  - Malignancies with neuroendocrine (NE) features such as medullary thyroid cancer
      (MTC) and small cell lung cancer (SCLC) are prototypic neoplasms arising from
      peripheral endocrine cells. The mechanisms that regulate the NE phenotype in
      these tumors and their cellular precursors are not well understood. However, a
      basic helix-loop-helix transcription factor that is homologous to Drosophila
      neural fate determination proteins may have a central role. Human achaete-scute
      homologue-1 (hASH1), a human homologue of the Drosophila achaete-scute complex,
      is highly expressed in MTC, SCLC, and pheochromocytomas. To determine what
      mechanisms allow constitutive expression of hASH1 in NE tumors, we cloned human
      genomic DNA fragments containing the hASH1 gene and characterized its promoter
      region. We show that hASH1 expression is restricted to NE cell lines by a
      transcriptionally regulated mechanism. Dual promoters initiate hASH1
      transcription, with the predominant site being an evolutionarily conserved
      initiator (INR) element. Transient transfection studies provide evidence for a
      generalized enhancer region that has high activity in all cell lines tested.
      Restriction of hASH1 expression to NE tumor cells depends on two tissue-specific
      repressor regions, present in the proximal and distal (> 13.5 kb) 5'-flanking
      region. Understanding the mechanisms of tissue-specific control of hASH1 gene
      expression provides a useful model to explore regulatory cascades influencing
      both normal nervous system development and the NE phenotype of tumors such as MTC
      and SCLC.

PMID- 9186002
TI  - Retinoic acid induces signal transducer and activator of transcription (STAT) 1,
      STAT2, and p48 expression in myeloid leukemia cells and enhances their
      responsiveness to interferons.
AB  - IFNs are antiproliferative cytokines that have growth-inhibitory effects on
      various normal and malignant cells. Therefore, they have been used in the
      treatment of certain forms of cancer, such as chronic myelogenous leukemia and
      hairy cell leukemia. However, there is little evidence that IFNs would be
      effective in the treatment of acute myelogenous leukemia, and molecular
      mechanisms underlying IFN unresponsiveness have not been clarified. Here we have
      studied the activation and induction of IFN-specific transcription factors signal
      transducer and activator of transcription (STAT) 1, STAT2, and p48 in all-trans
      retinoic acid (ATRA)-differentiated myeloid leukemia cells using promyelocytic
      NB4, myeloblastic HL-60, and monoblastic U937 cells as model systems. These cells
      respond to ATRA by growth inhibition and differentiation. We show that in
      undifferentiated NB4 cells, 2',5'-oligoadenylate synthetase and MxB gene
      expression is not activated by IFN-alpha, possibly due to a relative lack of
      signaling molecules, especially p48 protein. However, during ATRA-induced
      differentiation, steady-state STAT1, STAT2, and especially p48 mRNA and
      corresponding protein levels were elevated both in NB4 and U937 cells, apparently
      correlating to an enhanced responsiveness of these cells to IFNs. ATRA treatment
      of NB4 cells sensitized them to IFN action as seen by increased IFN-gamma
      activation site DNA-binding activity or by efficient formation of IFN-alpha
      specific ISGF3 complex and subsequent oligoadenylate synthetase and MxB gene
      expression. Lack of p48 expression could be one of the mechanisms of
      promyelocytic leukemia cell escape from growth-inhibitory effects of IFN-alpha.

PMID- 9186003
TI  - Down-regulation of cyclin A gene expression upon genotoxic stress correlates with
      reduced binding of free E2F to the promoter.
AB  - Treatment of mammalian cells by DNA-damaging agents leads to various cellular
      responses. At sufficiently high dosage, cisplatin blocks cell proliferation and
      finally kills cells; this effect is the basis for its widespread use as an
      anticancer drug. Cisplatin-treated cells arrest in the G1 phase of the cell
      cycle, most likely due to a signal generated by the stabilization of p53 and the
      subsequent induction of p21WAF-1/Cip1. We show here that cisplatin-treated
      mammalian cells accumulate normal levels of cyclin D1 and cyclin E but fail to
      produce cyclin A. The block to cyclin A gene expression occurs at the level of
      transcription and is mediated by an E2F binding site in the cyclin A promoter. It
      is shown here that, upon cisplatin treatment, transcriptionally active free E2F
      becomes limiting, coincident with the accumulation of hypophosphorylated species
      of the retinoblastoma protein family. Immunoprecipitation experiments suggest
      that the loss of free E2F results, at least in part, from the sequestration of
      E2F-4/DP-1 heterodimers by p107. A role for the kinase inhibitor p21WAF-1/Cip1 in
      repression of the cyclin A promoter is supported by our finding that ectopic
      expression of p21WAF-1/Cip1 is sufficient to inhibit transcription from the
      cyclin A gene, dependent on the E2F site. The data establish the E2F site in the
      human cyclin A promoter as a key target for the signaling pathway leading to G1
      arrest in response to DNA damage by cisplatin and potentially other genotoxic
      agents.

PMID- 9186004
TI  - A switch in the phosphorylation state of the dimeric form of the Meg1 protein
      correlates with progression through meiosis in the mouse.
AB  - meg1 is a murine gene that encodes for a 0.75-kb transcript that in mature male
      mice is expressed exclusively in the testis. This transcript starts to accumulate
      in early stages of the first meiotic prophase and reaches a peak in pachytene
      spermatocytes. In females, meg1 transcripts are detectable only in ovaries of
      embryos with oocytes that have reached the prophase stage of the first meiotic
      division. No meg1 transcripts can be detected in adult ovaries. meg1 is,
      therefore, assumed to be involved with meiotic processes. In this study, specific
      polyclonal antibodies were raised against the Meg1 protein and were used to
      demonstrate that this protein is indeed specific to the testis. Western blot
      analysis of immunoprecipitated Meg1 protein revealed multiple bands (in the range
      of M(r) 12,000-18,000), some of which where recognized by anti-phosphotyrosine
      antibodies, suggesting that in vivo, Meg1 appears in multiple phosphorylated
      forms. Western analysis of purified M(r) 15,000 recombinant Meg1 protein, under
      nonreducing conditions, revealed an apparent M(r) 31,000 band, suggesting that
      Meg1 can form a homodimer via S-S bonds. Analysis of Meg1 from postnatal testes
      at different developmental stages revealed that in addition to the multiple
      monomeric forms of Meg1, two dimeric forms of about M(r) 31,000 and M(r) 32,000
      were consistently detected. A developmentally regulated switch in the relative
      predominance of these two dimeric forms was apparent. The M(r) 31,000 form, which
      is tyrosine phosphorylated, becomes the predominant form once the cells enter
      meiosis. These results suggest that dimerization and
      phosphorylation/dephosphorylation reactions might regulate the function of Meg1
      during meiosis.

PMID- 9186005
TI  - Cross-linking of integrins induces tyrosine phosphorylation of the proto-oncogene
      product Vav and the protein tyrosine kinase Syk in human factor-dependent myeloid
      cells.
AB  - Attachment to extracellular matrix is important in the regulation of
      proliferation and differentiation of hematopoietic stem and progenitor cells.
      Post-ligand occupancy events of integrin receptors in myeloid cells are largely
      unknown. We examined early signaling events after stimulation of integrin
      receptors (outside-in signal) using a cross-linking system in a growth factor
      dependent myeloid cell line, M07e, alpha 4, alpha 5, and beta 1 integrin cross
      linking induced a similar pattern of transient tyrosine phosphorylation of
      cellular proteins. The approximate molecular weights of these phosphoproteins
      were M(r) 150,000, M(r) 120,000-125,000, M(r) 95,000, M(r) 70,000, M(r) 60,000,
      and M(r) 40,000-50,000. Vav, Syk, and Erk2 were identified as some of the
      tyrosine-phosphorylated proteins, and their weights were M(r) 95,000, M(r)
      70,000, and M(r) 40,000-50,000, respectively. Erk2 and Vav were also tyrosine
      phosphorylated by stimulation with Steel factor (SLF) and granulocyte macrophage
      colony-stimulating factor, whereas tyrosine phosphorylation of Syk was not
      induced by stimulation with these cytokines. The degree of tyrosine
      phosphorylation of Vav through integrin engagement was almost equal to that by
      SLF stimulation, whereas that of Erk2 was much weaker than with SLF stimulation.
      Upon integrin engagement, antibodies raised against Syk coprecipitated several
      tyrosine-phosphorylated proteins. In vitro binding assays demonstrated that,
      among these Syk-associated proteins, pp40, which differed from Erks, Crk, and
      Crkl, binds Syk through SH2 domains of Syk and is a prominent tyrosine
      phosphorylated protein in integrin cross-linked cells. These results suggest that
      tyrosine phosphorylation of Vav and Erk2 in myeloid cells might be regulated by
      both integrins and cytokines in the bone marrow microenvironment, whereas Syk
      might be involved in a distinct pathway from the shared between integrins and
      cytokines in myeloid cells.

PMID- 9186006
TI  - Researchers in cell motility and the cytoskeleton can play major roles in
      understanding AIDS.

PMID- 9186007
TI  - Quantitative analysis of Caenorhabditis elegans sperm motility and how it is
      affected by mutants spe11 and unc54.
AB  - The sperm of Caenorhabditis elegans translocate in a fashion similar to sperm of
      Ascaris suum even though their pseudopods are longer, more plastic in shape, and
      form multiple expansions zones around their perimeter. Mutants in spe-11 form
      primary spermatocytes with a defective perinuclear region, but the resulting
      spermatozoa can still crawl and fertilize eggs. However, the resultant zygotes
      die due to the absence of sperm-supplied spe-11. Computer-assisted analysis of
      translocating spe-11 sperm reveals a novel defect in the dynamic morphology of
      their pseudopods. A similar analysis of the C. elegans mutant unc-54, which lacks
      the most abundant isoform of myosin II, reveals no defect in sperm motility, as
      expected, since C. elegans sperm have substituted the protein MSP for actin in
      the process of pseudopod expansion. These results reveal an unexpected defect in
      the dynamic morphology of pseudopods of spe-11 sperm. This defect, however, does
      not significantly affect crawling velocity, and it demonstrates how computer
      assisted motion analysis systems can reveal subtle behavioral phenotypes in C.
      elegans mutant spermatozoa.

PMID- 9186008
TI  - Flagellar photoresponses of ptx1, a nonphototactic mutant of Chlamydomonas.
AB  - Phototaxis in wild-type Chlamydomonas cells is probably the result of four single
      photoresponses in the flagella, inverse in the cis (near the eyespot) and in the
      trans flagellum and also inverse by step-up (increase of) and step-down (decrease
      of) light stimulation as experienced by the eyespot during rotation of the cell
      [Ruffer and Nultsch, 1991: Cell Motil. Cytoskeleton 18:269-278]. Two inverse sets
      of the four responses are supposed to be the cause for positive and negative
      phototaxis. The relevant flagellar responses consist of shifts of the front
      amplitude of the breaststroke beats. As single flagellar responses cannot be
      called "phototactic" they are termed "breaststroke flagellar photoresponses." The
      mutant strain ptx1 is defective in phototaxis but displays photoshocks [Horst and
      Witman, 1993: J. Cell Biol. 120:733-741]. Analysis of flagellar beat patterns in
      high-speed records of ptx1 cells held on micropipettes shows that breaststroke
      flagellar photoresponses exist in this mutant in spite of the loss of phototaxis.
      It is the cis/trans differentiation that is lost in ptx1: both flagella always
      respond in the same way and not inversely as in wild-type cells. Equal shifts of
      beat amplitude cannot cause a turn of the cell, which explains why phototaxis is
      not seen in ptx1 and supports the model suggested for positive and negative
      phototactic steering. In wild-type cells front amplitude changes are connected
      with beat period changes, which also occur in ptx1 cells and suggest that both
      flagella respond like wild-type trans flagella. Divergencies in the shock
      response of ptx1 cells, beat period reduction, and coordination changes may
      support the notion that cis flagellar specialization is lost and that ptx1
      possesses, so to speak, two trans and no cis flagellum. Therefore, the mutant
      strain ptx1 might be useful for studying molecular and functional peculiarities
      of the two flagella.

PMID- 9186009
TI  - Sequence analysis of the Chlamydomonas reinhardtii flagellar alpha dynein gene.
AB  - Flagellar outer row dynein ATPases have been used extensively as model systems
      for studies of microtubule-based motility. Previously full-length sequences were
      only available for two of the three catalytic heavy-chain subunits (DHCs) of this
      enzyme. We have completed the sequence of an 18-kb genomic region encoding the
      Chlamydomonas reinhardtii flagellar outer row dynein alpha heavy chain. Unlike
      the beta- and gamma-subunits, DHC alpha is not required for assembly of other
      outer row dynein proteins, except for a tightly associated light chain, and thus
      occupies a unique position within this enzyme complex. The predicted 4,499
      residue protein retains sequence homology to other dynein heavy chains throughout
      its central and C-terminal regions but lacks homology to any other dyneins in the
      first 1,000 amino acids, which may account for its unusual assembly properties.
      This N-terminal domain of DHC alpha contains a repetitive sequence rich in
      alanines, prolines, and glutamic acids. Within the more homologous C-terminal
      region, which includes the catalytic domain, three short sequences unique to DHC
      alpha may account for its specific catalytic properties and in vivo
      phosphorylation pattern.

PMID- 9186010
TI  - Effects of shaker-1 mutations on myosin-VIIa protein and mRNA expression.
AB  - Numerous mammalian diseases have been found to be due to mutations in components
      of the actin cytoskeleton. Recently, mutations in the gene for an unconventional
      myosin, myosin-VIIa, were found to be the basis for the deafness and vestibular
      dysfunction observed in shaker-1 (sh1) mice and for a human deafness-blindness
      syndrome, Usher syndrome type 1B. Seven alleles of sh1 mice were analyzed to
      assess the affects of different myosin-VIIa mutations on both gene expression and
      tissue function. Myosin-VIIa is expressed in the inner ear and the retina, as
      well as the kidney, lung, and testis. Northern blot analysis indicated that
      myosin-VIIa mRNA expression, size, and stability were unaffected in the seven sh1
      alleles. Immunoblot analysis showed that all seven alleles expressed some full
      length myosin-VIIa protein. The range of expression, however, ran from sh1
      [original], which expressed wild-type levels of protein, to two strains,
      sh1(4494SB) and sh1(4626SB), which expressed less than 1% of the normal level of
      myosin-VIIa protein. For the three alleles of sh1 that have been characterized
      and that have mutations in the motor domain, sh1 [original], sh1(816SB) and
      sh1(6J), the level of protein expression observed in these sh1 alleles correlated
      well with the predicted effects of the mutations on motor function. No change in
      retinal or testicular structure was observed at the light microscopic level
      during the life span of the seven sh1 alleles. Myosin-VIIa protein, when
      detectable, was observed to locate properly in the sh1 mice. On the basis of
      these results, we propose that the mutations in myosin-VIIa in the sh1 alleles
      leads to both motor dysfunction and to a protein destabilization phenotype.

PMID- 9186011
TI  - Reactivation of cell surface transport in Reticulomyxa.
AB  - Granuloreticulosean protists transport particles (e.g., bacteria, algae, and sand
      grains) along the outer surfaces of their pseudopodia. This cell surface
      transport plays a vital role in feeding, reproduction, shell construction, and
      locomotion and can be visualized by the movements of extracellularly adherent
      polystyrene microspheres (i.e., latex beads). Our videomicroscopic analyses of
      transport associated with the pseudopodia of Reticulomyxa filosa revealed two
      distinct types of both intracellular and cell surface transport: (1) saltatory,
      bidirectional transport of individual or clustered organelles and/or surface
      attached particles, and (2) continuous, unidirectional bulk or "resolute" motion
      of aggregated organelles and/or surface-bound particles. Organelles and surface
      attached polystyrene microspheres remained firmly attached to the microtubule
      cytoskeletons of detergent-extracted pseudopodia. Both saltatory and resolute
      organelle and surface transport reactivated upon the addition of 0.01-1.0 mM ATP.
      At 1 mM ATP, the velocities of reactivated saltatory transport were
      indistinguishable from those observed in vivo. The reactivated transport was
      microtubule-dependent and was not inhibited by incubation with Ca(2+)-gelsolin
      under conditions that abolish rhodamine-phalloidin detection of actin filaments.
      These findings provide further support that both intracellular organelle and
      membrane surface transport are mediated by a common mechanism, and establish
      Reticulomyxa as a unique model system to further study the mechanochemistry of
      cell surface transport in vitro.

PMID- 9186012
TI  - Characterization of gamma-tubulin complexes in Aspergillus nidulans and detection
      of putative gamma-tubulin interacting proteins.
AB  - gamma-Tubulin is central to the nucleation of microtubule assembly in vivo.
      Although it is most obviously located at microtubule organizing centers, it is
      also found in soluble cytoplasmic complexes. Characterizing these complexes and
      identifying proteins that interact with gamma-tubulin in vivo will be necessary
      if gamma-tubulin function is to be understood fully. We have begun to investigate
      soluble complexes of gamma-tubulin in Aspergillus nidulans, the organism in which
      gamma-tubulin was discovered and in which a great deal of genetic and molecular
      genetic analysis of gamma-tubulin has been carried out. We find that
      approximately 32% of the gamma-tubulin in A. nidulans is soluble. Sucrose density
      gradients revealed that the soluble gamma-tubulin is in 8-20S complexes with
      little or no monomeric gamma-tubulin present. In the presence of 0.5 M KCl the
      average size of the complexes decreased and a peak was present between 4S and
      11S. Cross-linking experiments with a zero-length cross-linker suggest that gamma
      tubulin in isolated nuclei and in intact hyphae interacts physically with three
      proteins with molecular weights of approximately 105, 95, and 80 kDa.

PMID- 9186013
TI  - Bacteroides fragilis toxin rearranges the actin cytoskeleton of HT29/C1 cells
      without direct proteolysis of actin or decrease in F-actin content.
AB  - Enterotoxigenic strains of B. fragilis associated with childhood diarrhea produce
      a 20 kD zinc metalloprotease toxin (BFT). BFT is reported to cleave G-actin in
      vitro and also causes dramatic rounding and rearrangement of the F-actin
      cytoskeleton in human intestinal epithelial cell lines (HT29) and HT29/C1). To
      test the hypothesis that the proteolysis of cellular actin by BFT in vivo may
      contribute to these alterations in morphology and cytoskeletal architecture, we
      assessed the F-actin content and the arrangement of the F- and G-actin
      cytoskeleton in BFT-treated HT29/C1 cells by spectrofluorimetry, confocal
      microscopy, and immunoblotting. BFT-treated cells were compared to cells treated
      with C. difficile toxin A (CDA) or cytochalasin D. Using spectrofluorimetric
      quantification, the F-actin content of BFT- and cytochalasin D-treated cells was
      unchanged in contrast to a significant decrease in CDA-treated cells. By confocal
      microscopy, the arrangement of F- and G-actin in all treated cells was markedly
      different than control cells. There was no change in the immunoblotting pattern
      of actin in the Triton-soluble or -insoluble cellular fractions of BFT-treated
      HT29/C1 cells. We conclude that BFT alters the F- and G-actin cytoskeletal
      architecture of HT29/C1 cells without direct proteolysis of actin or decrease in
      F-actin content.

PMID- 9186015
TI  - Cyberpain.

PMID- 9186014
TI  - Differential colocalization of profilin with microfilaments in PtK2 cells.
AB  - Profilins are thought to be involved in the control of actin dynamics in
      eukaryotic cells. In accordance with this concept, profilin was found to be
      colocalized with the cortical microfilament webs in leading lamellae of
      locomoting and spreading fibroblasts. However, so far, there is little
      information on the distribution of profilin in other cell types. In this study,
      we report on the colocalization of profilin with various microfilament
      suprastructures in the epithelial cell line PtK2. This cell line, which is
      derived from rat kangaroo, contains a profilin sharing an N-terminal epitope with
      bovine and human profilin I, as seen by immunoblotting with monoclonal
      antibodies. By using immunofluorescence in conjunction with conventional
      fluorescence microscopy and confocal laser-scanning microscopy, we found profilin
      in ruffling areas of the peripheral lamellae and nascent stress fibers of
      spreading cells, whereas the peripheral belts of stationary cells growing in
      epithelioid sheets lacked profilin staining. In these cells, profilin was
      primarily distributed in a fine reticular or vesicular network that was not
      related to the microfilament system. Conspicuously low levels of profilins was
      not related to the contractile ring of mitotic cells. This was found for
      different fixation protocols and antibodies of the IgG and IgM type,
      respectively, indicating that lack of staining of the cleavage furrow was not due
      to antibody penetration problems. Depending on the fixation protocol, the nuclear
      matrix appeared strongly positive or negative for profilin. Cells microinjected
      with birch pollen profilin and labeled with a birch profilin-specific monoclonal
      antibody corroborated the results obtained with the endogeneous protein: The
      injected profilin was targeted to the cortical web and to nascent stress fibers
      of spreading cells but not to the cleavage ring of mitotic cells. These results
      suggest that high concentrations of a profilin I homologue are preferentially
      located with those microfilament suprastructures in PtK2 cells that are subject
      to rapid modulation by external signals.

PMID- 9186016
TI  - Biobehavioral pain research: a multi-institute assessment of cross-cutting issues
      and research needs.
AB  - In 1994 ten NIH institutes sponsored an interagency workshop focusing on
      biobehavioral pain research. The workshop had three major goals: (1) to review
      the current status of biobehavioral pain research (2) to identify critical
      research needs, and (3) to enhance interdisciplinary and interagency cooperation
      in pain research. The purpose of this article is to summarize the presentations
      at this meeting and to highlight some of the key research recommendations.
      Research topics addressed include (a) understanding critical interfaces between
      biology and behavior; (b) pain, suffering, and emotion; (c) pain and behavior;
      (d) behavior-related interventions; (e) commonalities and differences in pain
      expression, experience, and treatment; and (f) pain in special populations. The
      article concludes with a summary of NIH pain research activities that have taken
      place since the workshop.

PMID- 9186017
TI  - Motivational correlates of self-reported persistent pain in young adults.
AB  - OBJECTIVE: We sought to illustrate that personal goals can provide a meaningful
      context within which to interpret physical pain and that persistent (nonclinical)
      pain correlates with dysfunctional goal evaluation for young adults. DESIGN: A
      total of 127 college students reporting either no pain or persistent physical
      pain completed the Goal System Assessment Battery, a set of questionnaires
      designed to gauge stable and accessible representations of self-regulated goal
      pursuit. RESULTS: The results supported the general contention that persons
      experiencing persistent pain (at subclinical levels) tend to evaluate their
      important life goals in a "problematic" fashion. Specifically, the presence of
      persistent pain was associated with lower ratings of self-efficacy, self
      monitoring, self-reward, and less positive arousal. CONCLUSIONS: The pattern of
      goal construal produced by this young and generally healthy group of college
      students reflects cognitive-motivational dysfunctions possibly presaging pain
      schemes in later life.

PMID- 9186018
TI  - The stability of pain coping strategies in young children adolescents, and adults
      with sickle cell disease over an 18-month period.
AB  - OBJECTIVE: The current study assessed stability of pain coping strategies over an
      18-month period in adults, adolescents, and young children with sickle cell
      disease. DESIGN: Eighteen-month longitudinal study. Assessments of coping
      strategies were done at baseline, 9 months, and 18 months. PATIENTS: A total of
      141 patients with sickle cell disease (SCD) presenting to adult and pediatric
      sickle cell clinics for regularly scheduled check-ups. OUTCOME MEASURES: Coping
      Strategy Questionnaire subscales (Coping Attempts, Negative Thinking, and Illness
      Focused Strategies). RESULTS: pearson Product-Moment correlation coefficients
      comparing baseline and 18-month follow-up coping data were highly significant for
      Coping Attempts and Negative Thinking/Illness Focused Strategies for adults. For
      young children, the 18-month follow-up scores on Negative Thinking were
      significantly correlated with baseline scores, however, no other 18-month
      correlations were significant. The results from the adolescent subset of subjects
      indicated no significant correlations on any of the coping strategies from
      baseline to 18-month-follow-up. Stability was also assessed using intraclass
      correlations, which incorporates more than two test-retest values on the same
      subjects. These analyses confirmed that coping strategies in adults were highly
      stable, whereas for children and adolescents, there was instability ANOVAs
      indicated that adolescents scored significantly higher than young children on
      Negative Thinking and Illness-Focused Strategies at baseline and follow-up.
      CONCLUSIONS: As compared with the highly stable coping evidenced in adults with
      SCD, coping in children and adolescents with SCD is more variable. Thus,
      interventions should target children early before maladaptive coping patterns
      become entrenched.

PMID- 9186019
TI  - Chronic pain-associated depression: antecedent or consequence of chronic pain? A
      review.
AB  - OBJECTIVE: To determine the current status for the association of chronic pain
      and depression and to review the evidence for whether depression is an antecedent
      or consequence of chronic pain (CP). DESIGN: A computer and manual literature
      review yielded 191 studies that related to the pain-depression association. These
      reports were reviewed and sorted into seven categories relating to the topic of
      this paper. Eighty-three studies were then selected according to inclusion
      criteria and subjected to a structured review. SETTING: Any medical treatment
      setting including pain treatment as inclusion criteria for selection of studies.
      PATIENTS: Any patients with any type of chronic pain. RESULTS: The reviewed
      studies were consistent in indicating that there is a statistical relationship
      between chronic pain and depression. For the relationship between pain and
      depression, there was greater support for the consequence and scar hypotheses
      than the antecedent hypothesis. CONCLUSIONS: Depression is more common in chronic
      pain patients (CPPs) than in healthy controls as a consequence of the presence of
      CP. At pain onset, predisposition to depression (the scar hypothesis) may
      increase the likelihood for the development of depression in some CPPS. Because
      of difficulties in measuring depression in the presence of CP, the reviewed
      studies should be interpreted with caution.

PMID- 9186020
TI  - Biological barriers to paediatric pain management.

PMID- 9186021
TI  - A longitudinal study of pain: reported pain from middle age to old age.
AB  - OBJECTIVE: Describe patterns of pain reporting over a span of 24 years. DESIGN:
      Individuals were interviewed on four occasions (1968, 1974, 1981, 1992).
      PARTICIPANTS: Representative sample (n = 321) of the Swedish population aged 53
      63 at baseline. MEASURES: Self-reported pain in the chest, abdomen, and
      musculoskeletal system (back or hips, shoulders, hands, elbows, legs, or knees).
      RESULTS: Less than 1% reported chest or abdominal pain on all four occasions.
      Whereas 21.8% of the sample reported musculoskeletal pain on all four occasions.
      More than half of the sample reported some kind of pain on three or four
      occasions. Women reported more severe and more persistent pain compared with men.
      There were more people who developed pain during the 24-year period than there
      were who became pain free. An increase in pain was equally common for chest and
      musculoskeletal pain, but a decrease in pain was much more common for
      musculoskeletal pain than chest pain. CONCLUSIONS: Cross-sectional studies have
      shown differing age patterns in pain. This longitudinal study demonstrates
      different patterns for men and women and for different pain localities.

PMID- 9186022
TI  - Prescription opiate abuse in chronic pain patients: clinical criteria, incidence,
      and predictors.
AB  - OBJECTIVES: Opiates are commonly used to treat patients with chronic nonmalignant
      pain. There is much controversy over the definition, incidence, and risk factors
      of prescription opiate abuse in chronic pain treatment. The present study, done
      at the Seattle VA Medical Center, was designed to create opiate abuse criteria,
      test inter-rater reliability of the criteria, apply the criteria to a group of
      chronic pain patients, and correlate the risk of opiate abuse with the results of
      alcohol and drug testing. DESIGN/OUTCOME MEASURES: A committee of experienced
      pain providers designed a five-point prescription opiate abuse checklist based on
      DSM-III-R parameters. The criteria were then applied to patients enrolled in the
      pain clinic. The reliability of the criteria were determined using two providers
      who were familiar with every patient in the clinic. Drug, alcohol, and
      psychosocial testing were correlated with the risk of opiate abuse. RESULTS: A
      total of 19% (76/403) of all pain clinic patients were using chronic opiates.
      Thirty-four percent (26/76) met one, and 27.6% (21/76) met three or more of the
      abuse criteria. The criteria had an inter-rater reliability of > 0.9. There were
      no differences between chronic opiate users (n = 76) and opiate abusers (n = 21)
      for a history of drug or alcohol abuse or on psychosocial testing. CONCLUSIONS:
      Prescription opiate abuse criteria for use in patients with chronic nonmalignant
      pain were designed. The criteria had good reliability and can be applied during
      normal clinic interactions. The percentage of chronic opiate users who become
      opiate abusers in pain treatment is within the range reported by others. Past
      opiate or alcohol abuse or psychosocial testing on clinic admission failed to
      predict who would become an opiate abuser. The criteria can be used to identify
      patients who will subsequently require more intensive treatment or intervention
      or can be used as an outcome to measure to test the effectiveness of treatment
      strategies.

PMID- 9186023
TI  - CSQ: five factors or fiction?
AB  - OBJECTIVE: The Coping Strategies Questionnaire (CSQ), a rationally constructed
      pain coping assessment instrument, was conceived to measure the extent to which
      patients used six different cognitive coping strategies and two behavioral coping
      strategies. A number of studies have factor analyzed the original scales but have
      not found a reliable factor structure. Recent studies by Turtle et al. and
      Swartzman et al. have obtained a five-factor solution performing exploratory
      factor analysis on the individual items. Robinson and associates from the
      University of Florida performed an item level exploratory factor analysis on a
      much larger sample (n = 965) and found a six-factor solution that was relatively
      supportive of the original rationally derived scales. The purpose of the present
      investigation was to perform a confirmatory factor analysis using the LISREL
      structural equation modeling program to compare these three different factor
      structures. PATIENTS: A sample of 472 chronic patients was used. RESULTS AND
      CONCLUSIONS: The results indicated that the Florida six-factor model was a better
      fit to the sample data than either of the five-factor models. Creation of the
      Coping Strategy Questionnaire Revised (CSQ-R), which retains 27 of the original
      items, is suggested.

PMID- 9186024
TI  - Assessing depression among persons with chronic pain using the Center for
      Epidemiological Studies-Depression Scale and the Beck Depression Inventory: a
      comparative analysis.
AB  - OBJECTIVE: This study examined the ability of two self-report questionnaires, the
      Beck Depression Inventory (BDI) and the Center for Epidemiological Studies
      Depression Scale (CES-D), to discriminate between chronic pain patients with and
      without major depression. Since previous research has suggested that medical
      conditions such as chronic pain can influence the endorsement of items that
      measure neurovegetative symptoms of depression, the accuracy of each of these
      questionnaires was also assessed eliminating these items. SUBJECTS: These
      included 132 consecutive patients with chronic pain, 44 of whom were diagnosed as
      suffering from major depression according to DSM-IV criteria. METHODS: Patients
      were administered a battery of questionnaires that included the CES-D and BDI.
      They were also interviewed by a clinical psychologist to determine the presence
      or absence of major depression. RESULTS: Both questionnaires were able to
      discriminate significantly between persons with and without major depression.
      Removal of the somatic items on each questionnaire did not improve their
      accuracy. Discriminant function analysis revealed an optimal cut-off score of 21
      for the BDI, and 27 for the CES-D. Overall hit rates at these cut-offs for the
      two questionnaires were comparable, while the CES-D had somewhat better
      sensitivity (81.8% vs. 68.2%). Conversely, the BDI had slightly better
      specificity (78.4% vs. 72.7%). CONCLUSION: The results suggest that both
      questionnaires have good predictive validity among chronic pain patients, and
      decisions regarding the use of one questionnaire rather than the other may depend
      upon the goals of the user and the setting within which the questionnaire is
      used.

PMID- 9186026
TI  - Living with chronic pain.

PMID- 9186025
TI  - Hematuria-loin pain syndrome: its existence as a discrete clinicopathological
      entity cannot be supported.
AB  - OBJECTIVE: To (a) review existing literature and current concepts on Hematuria
      Loin Pain Syndrome (HLPS) and (b) to describe seven cases of this syndrome.
      PATIENTS AND SETTING: Seven HLPS patients seen over a period of 8 years by the
      pain and nephrology services of the Toronto Hospital, Toronto, Ontario, Canada.
      METHODS AND RESULTS: Retrospective analysis was performed. All patients were
      remarkable for the variability of clinical presentation, pain characteristics,
      and dissociation of pain and hematuria occurrence. Routine renal investigations
      revealed different benign kidney pathologies in 5 of 7 patients. All patients,
      however, displayed variable combinations of personality factors, drug seeking
      behaviour, psychopathology, and presence of significant psychosocial stressors.
      Four cases were managed conservatively with antidepressants, anxiolytics, and
      supportive counseling and did very well despite persistent hematuria in two.
      CONCLUSIONS: HLPS does not constitute a distinct clinicopathological entity. In a
      minority of cases only underlying kidney pathology is related to pain, and in
      many cases psychosocial stressors and underlying psychopathology may play a
      significant role in the reported disabling pain. A concerted
      medical/psychological approach is advocated.

PMID- 9186027
TI  - The role of exercise for carpal tunnel syndrome.

PMID- 9186028
TI  - Psychiatrists vs. psychologists.

PMID- 9186029
TI  - MRA image production and display.
AB  - Magnetic resonance angiography (MRA) refers to a collection of imaging techniques
      which accentuate the signal intensity of flowing blood and suppress the signal
      intensity of stationary tissues. The resulting images are processed to resemble
      conventional catheter angiograms but carry fundamentally different information
      which is derived from flow rather than anatomy. All MRA techniques are subject to
      a variety of artifacts can stimulate pathology. A knowledge of the techniques
      used to produce and display MR angiographic images is essential for their
      accurate interpretation.

PMID- 9186030
TI  - MRA in cerebrovascular disease.
AB  - Stroke is a major cause of disability and death each year in the United States.
      Most cases result from atherosclerotic disease at the carotid bifurcations. The
      risk of such events can be reduced by carotid endarterectomy in both symptomatic
      and asymptomatic patients with severe occlusive disease documented by imaging
      studies. A noninvasive means of determining the degree of stenosis is desirable
      due to morbidity, mortality, and cost associated with catheter angiography. At
      the present time the main role of MRA is as a screening test to determine who
      should undergo catheter angiography.

PMID- 9186031
TI  - MRA of intracranial aneurysms.
AB  - Most intracranial aneurysms are located in the circle of Willis. They occur in 5
      6% of the general population. Patients with intracranial aneurysm either present
      catastrophically with rupture of the aneurysm have aneurysms that are
      incidentally discovered. Prognosis is drastically different in each case, with a
      greater than 50% incidence of death if there is a rupture of the aneurysm. On the
      other hand, the surgical or endovascular mortality following treatment of an
      unruptured aneurysm is minimal, with good patient neurological outcome. In the
      appropriate clinical setting, it is important to find a screening study that can
      detect a cerebral aneurysm so that definitive cerebral angiography can be
      performed. The combination of magnetic resonance imaging (MRI) and magnetic
      resonance angiogram (MRA) can detect an aneurysm in 60-85% of cases. This
      screening test adds a few minutes of scanning time to the average MR examination.
      Magnetic resonance angiography techniques continue to improve with better
      gradients, enhanced sequences to detect flow and reduce flow-related artifacts,
      shorter echo times with possible use of echo-planar (short scanning time)
      techniques, and improved imaging matrix, and they may, in conjunction with
      computed tomographic angiography (CTA), become a reliable non-invasive technique
      for detection of intracranial aneurysm.

PMID- 9186032
TI  - MRA of vascular malformations.

PMID- 9186033
TI  - Magnetic resonance angiography in trauma.
AB  - Following blunt or penetrating trauma to the head and neck, a variety of
      traumatic vascular injuries may occur. Often the clinical presentation of a
      craniocervical arterial injury is delayed and neuroimaging studies are necessary
      to evaluate for delayed findings of intracranial infarction or hemorrhage. In
      this setting, magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA) may allow a prompt noninvasive diagnosis of craniocervical vascular injury.
      MRA may be helpful in selecting those patients requiring conventional angiography
      and allows a noninvasive follow-up evaluation of arterial injury following
      institution of therapy.

PMID- 9186034
TI  - MRA of cranial tumors and vascular compressive lesions.
AB  - Magnetic resonance angiography (MRA) and venography (MRV) are useful tools in the
      diagnosis and analysis of both intracranial and head and neck tumors. These
      procedures illuminate the three-dimensional relationships of the tumors and the
      adjacent cerebral vasculature. Contrast administration allows further analysis of
      these lesions. Research continues to improve the spatial resolution that may
      preclude conventional angiography. For the first time, MRA allows non-invasive
      diagnosis of neurovascular conditions such as trigeminal neuralgia and pulsatile
      tinnitus. This accurate diagnosis revolutionizes therapy. Although MRA has
      certain limitations, its role continues to expand. The value of MRA for diagnosis
      and treatment planning is paramount.

PMID- 9186035
TI  - Magnetic resonance angiography in children.
AB  - MRA in children utilizes the same pulse sequences used in adults, but for
      investigation of the differing forms of vascular pathology found in the pediatric
      population. Because of the extreme sensitivity of MRA to motion artifact,
      sedation is an important adjunct to the performance of diagnostic MRI and MRA in
      children. Because of the noninvasive nature of MRA, strictly diagnostic
      conventional angiography in children is uncommonly performed and frequently
      directed toward investigation and therapy of intracranial vascular malformations.
      Common indications for MRA in children include sickle cell vasculopathy, cerebral
      and posterior fossa infarction, tumors, vascular malformations, and follow-up of
      patients recently on extra corporeal membrane oxygenation (ECMO). Non-invasive
      follow-up subsequent to surgical or medical therapy of intra or extra cranial
      vascular pathology is another important use for MRA in children.

PMID- 9186036
TI  - MRA of venous sinus thrombosis.
AB  - Intracranial venous magnetic resonance angiography (MRA) provides excellent
      visualization of dural venous sinuses and large deep and superficial cerebral
      veins noninvasively. It is a very useful imaging technique to evaluate venous
      sinus thrombosis. It also provides the planning and monitoring endovascular
      thrombolytic treatment for dural sinus thrombosis. Familiarization with normal
      intracranial venous anatomy and its normal variants as well as recognition of its
      pitfalls and artifacts of the venous MRA techniques are critical for making
      interpretation of venous sinus thrombosis correctly.

PMID- 9186037
TI  - Spine MR angiography.
AB  - The use of MR angiography to evaluate spinal vessels is in an early stage of
      development. Both time-of-flight (3D) and phase-contrast (2D and 3D) techniques
      have been applied, and for both types of techniques, the vessels are best
      visualized following intravenous gadolinium administration. The vessels of
      interest are the millimeter-sized intradural arteries and veins, which are
      located on the cord surface and travel from the cord to the epidural space. Only
      the post gadolinium 3D TOF technique has been shown to display normal intradural
      vessels (thoracolumbar region), principally veins. Both TOF and PC techniques
      provide better delineation of enlarged intradural vessels associated with spinal
      vascular malformations than standard MR imaging alone. PC techniques are much
      less sensitive in detecting the arterial supply to dural arteriovenous fistula
      than intramedullary arteriovenous malformation. The TOF technique can predict the
      foraminal level of a dural fistula when an enlarged medullary vein, resulting
      from retrograde drainage, is present. MR angiography, in conjunction with MR
      imaging, is now suggested for screening of suspected spinal vascular
      malformation. Other applications such as vascular tumors and arterial or venous
      occlusive disease are under investigation.

PMID- 9186038
TI  - Extension of fundamental stroke research into clinical care.
AB  - Clinical efforts in stroke prevention have measurably reduced the incidence of
      stroke in persons experiencing a number of risk factors. Clinical efforts to
      reduce stroke size once the process starts, however, have been disappointing. A
      variety of agents aimed at blocking the effects of excitotoxic neurotransmitters
      or interfering with intracellular calcium entry have been tested but with little
      success on clinical outcome. Satisfactory explanation of the paradox between
      animal and clinical outcome studies has not been forthcoming. Accordingly,
      clinical investigators are exploring the potential value of surgical craniectomy
      in efforts to improve the presently devastated outcome that marks the course of
      severe, large acute cerebral infarctions.

PMID- 9186039
TI  - Molecular and biochemical events within the brain subjected to cerebral ischemia
      (targets for therapeutical intervention).
AB  - We review the molecular and biochemical events that occur within the brain during
      cerebral ischemia, based on recent investigations of focal cerebral ischemia
      models. Occlusion of the middle cerebral artery in rats produces focal ischemia.
      In contrast to the core where ischemia is severe and infarction develops rapidly,
      areas surrounding the core (called the penumbra) show a more moderate decrease of
      blood flow and can tolerate longer durations of ischemic stress. Reperfusion and
      pharmacological interventions can help to salvage the penumbra. Ischemic insult
      alters the genomic properties of the brain cells and selective production of heat
      shock proteins can be seen. Heat shock proteins are necessary in the repair of
      cell integrity, and is thought to be induced as a rescue program. Pre-ischemic
      induction of these proteins is known to cause ischemic tolerance, and methods to
      manipulate genes into inducing HSPs may be effective in protecting neurons from
      ischemia. Genes that promote apoptosis are also expressed after ischemia, and may
      cause secondary expansion of the infarction. Strategies to denote expression of
      these genes may be effective in reducing ischemic neuronal death. Activation of
      the inflammatory cells such as neutrophils and macrophages, in the ischemic
      region, may cause further post-ischemic damage. Investigations on the role and
      mechanics of inflammatory systems in ischemic neuronal injury may present a new
      target for therapeutic intervention against stroke.

PMID- 9186040
TI  - Mechanisms of neuroprotective drug actions.

PMID- 9186041
TI  - Role of Ca+2 and other second messengers in excitatory amino acid receptor
      mediated neurodegeneration: clinical perspectives.
AB  - Neurodegeneration associated with neurological disorders such as epilepsy,
      Huntington's Chorea, Alzheimer's disease, and olivoponto cerebellar atrophy or
      with energy failure such as ischemia, hypoxia, and hypoglycemia proceeds
      subsequent to overexposure of neurons to excitatory amino acids of which
      glutamate and aspartate may be quantitatively the most important. The toxic
      action of glutamate and aspartate is mediated through activation of glutamate
      receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA subtypes. Antagonists
      for these receptors can act as neuroprotectants both in in vitro model systems
      (e.g., cultured neurons) and in vivo. Activation of receptors leads to an
      increase in the intracellular Ca++ concentration and also to an increase in other
      second messengers such as cGMP. Thus, Ca++ channel antagonists may have
      neuroprotective action under certain conditions.

PMID- 9186042
TI  - Reperfusion damage following focal ischemia: pathophysiology and therapeutic
      windows.
AB  - The mechanisms of reperfusion damage following focal cerebral ischemia are not
      known in detail. Recent results, however, strongly suggest that reactive oxygen
      species (ROS), generated during the reperfusion period, may trigger the
      reperfusion injury. Mitochondrial calcium overload and a permeability transition
      (PT) of the inner mitochondrial membrane have been shown to play an important
      role in production of ROS by the mitochondria. The immunosuppressant cyclosporin
      A (CsA), which inhibits mitochondrial PT, protects against delayed neuronal
      necrosis of the hippocampal CA1 sector following transient forebrain/global
      ischemia. In focal ischemia ("stroke"), expression of adhesion molecules such as
      intercellular adhesion molecule-1 (ICAM-1) may lead to production of ROS by
      polymorphonuclear (PMN) leukocytes, which suggests the involvement of
      inflammatory and immunological reactions in reperfusion damage. The spin trap
      alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size and prevents a
      secondary mitochondrial dysfunction due to reperfusion, probably scavenging free
      radicals at the blood-endothelial cell interface.

PMID- 9186043
TI  - Towards the reduction of dynamic image data in position emission tomography
      studies.
AB  - In this study, we propose a method and investigate the reduction of dynamic image
      data with positron emission tomography (PET). The method is based upon the use of
      sampling schedules with a reduced number of scanning intervals and the use of an
      integral model in the cost function of nonlinear regression. The application of
      this method is illustrated by the problem of estimating the metabolic rate of
      glucose with the [18F]2-fluoro-2-deoxyglucose (FDG) model. Computer simulations
      were performed using various sampling schedules with scanning intervals of
      different lengths. The results were compared in terms of the accuracy and
      precision of the estimated parameters. It has been found that the use of sampling
      schedules with a reduced number of scanning intervals in conjunction with the
      integral model is very effective. The number of images in dynamic PET FDG studies
      can be reduced by a factor of 4.5 without losing the accuracy and precision of
      the parameter estimates.

PMID- 9186044
TI  - A tool for balancing activity from isotopes used for the radioactive microsphere
      method.
AB  - The radioactive microsphere method for determination of regional organ blood flow
      is widely used in experimental studies. The measurement error of this method in
      part depends on balanced activities from the set of nuclides used. Achieving even
      distribution of half-life corrected activity is tedious due to the many
      calculations needed and is limited by minimal and maximal allowable amounts of
      microspheres per injection. In two experiments we showed that incorrect planning
      of microspheres numbers can lead to invalidation of results. Therefore, we
      developed a program that allows optimization of half-life corrected activities
      and tested it on an experimental series of 16 dogs. Despite large discrepancies
      of specific activities of nuclides, storage times and half-lives, balancing
      activities with the program succeeded: on the average, the accumulated gamma
      spectra consisted of 22.3 +/- 6.9 85Sr, 18.9 +/- 6.8 141Ce, 10.7 +/- 6.2 51Cr,
      23.9 +/- 6.7 95Nb, 16.9 +/- 7.2 46Sc, and 7.3 +/- 2.7% 114mIn radiation,
      respectively.

PMID- 9186045
TI  - A novel tool for rapid prototyping and development of simple 3D medical image
      processing applications on PCs.
AB  - A 32-bit PC-based 3D medical image processing software package is presented. Its
      basic functions are the display and manipulation of medical images and the
      inclusion of user-written processing routines in C language. This software runs
      on inexpensive hardware and is easy to learn. It means the current needs of many
      research teams working in medical image processing.

PMID- 9186046
TI  - QAV: querying entity-attribute-value metadata in a biomedical database.
AB  - Entity-attribute-value (EAV) data organization is increasingly used for knowledge
      representation for complex heterogeneous biomedical databases. When delivered in
      relation form for production applications the simplicity of EAV storage is offset
      by difficulty of set-based data retrieval. We describe a client-server
      application, QAV, that is designed to perform set-based query on the Columbia MED
      dataset, a large medical metadata repository that has been the focus of much
      research. QAV interacts with the user through a graphical front end and generates
      a series of SQL statements that are sent to the server for the actual data
      retrieval.

PMID- 9186047
TI  - Individuals living in areas with high background radon: a GIS method to identify
      populations at risk.
AB  - OBJECTIVE: to identify and link populations and individuals that live within high
      risk areas. DESIGN: census registers and disease registers which contain data on
      individuals can only give aggregate statistics relating to postal code districts,
      town, county or state boundaries. However environmental risk factors rarely, if
      ever, respect these man-made boundaries. What is needed is a method to rapidly
      identify individuals who may live within a described area or region and to
      further identify the disease(s) occurring among these individuals and/or in these
      areas. METHOD: this paper describes a method for linking the standard registers
      available in Sweden, notably the residence-property addresses they contain and
      the geographical coordinate setting of these, to map the population as a point
      coverage. Using standard GIS methods this coverage could be linked, merged or
      intersected with any other map to create new subsets of population.
      Representation of populations down to the individual level by automatised
      spatialisation of available census data is in its simplicity a new informatics
      method which in the designated GIS medium adds a new power of resolution.
      RESULTS: We demonstrate this using the radon maps provided by the local communes.
      The Swedish annual population registration records of 1991 for the county of
      Ostergotland and the property register available at the Central Statistical
      Bureau of Sweden formed the main data sources. By coupling the address in the
      population register to the property register each individual was mapped to the
      centroid of a property. By intersecting the population coverage with the radon
      maps, the population living in high, normal or low risk areas was identified and
      then analysed and stratified by commune, sex and age. The resulting tables can be
      linked to other database registers, to visualise and analyse geographical and
      related patterns. The methodology can be adapted for use with any other
      environmental map or small area. It can also be expanded to the fourth dimension
      by linking likewise available migration information to generate immediately
      coordinate-set, accumulated exposition and similar data.

PMID- 9186048
TI  - Image processing for combined bright-field and reflection interference contrast
      video microscopy.
AB  - Image processing algorithms for automatic extraction of cell body contours and
      cell-substratum contacts from video images, which were obtained by bright-field
      microscopy and reflection interference contrast microscopy, respectively, are
      described. Double-view imaging, which combines these two optical techniques, is
      used to investigate the relationship between cell-to-substratum adhesion and cell
      shape changes during locomotion of the amoeboid cells of Dictyostelium
      discoideum. Contact areas of cells are extracted from reflection interference
      contrast images via a routine which performs binarisation on the basis of
      threshold estimation, as it is calculated by a histogram minimum method.
      Boundaries of cells are extracted from bright-field images by utilising and
      algorithm that includes background subtraction and binarisation based on texture
      discrimination by means of a rank operator.

PMID- 9186049
TI  - Toxopert-I: knowledge-based automatic interpretation of serological tests for
      toxoplasmosis.
AB  - Primary infection with Toxoplasma gondii, a parasite found in most regions of the
      world, is asymptomatic in more than 80% of cases. However, primary infection with
      Toxoplasma gondii in a pregnant woman might cause fetal infection and severe
      damage. Most cases do not require treatment. This applies to women without any
      infection (denoted as seronegative) and women who have acquired the infection
      before conception (denoted as latent). In contrast, women with postconceptual
      infection require immediate treatment to prevent or ameliorate fetal infection.
      We have developed an expert system, called Toxoport-I, designed for routine
      laboratory work, which automatically interprets serological test results of
      toxoplasma infection. By using the system the clinician can also examine
      questionable cases by interactively exploring possible results. We used a popular
      method of designing expert systems applied to medical interpretation and therapy
      advice, the rule-based one. In order to meet the requirements of automatic
      interpretation in toxoplasma serology the following characteristics were
      introduced: the interpretation of sequences of test results, the possibility of
      excluding inconsistent test results and the adaptability of the knowledge base. A
      decision graph that covers the different kinds of infections as well as therapy
      and recommendations for further tests was designed, implemented and was
      clinically tested by carrying out a retrospective study including 1000 pregnant
      women. A comparison of Toxoport-I and the clinician's interpretations yielded
      sensitivity and specificity rates of over 99% each.

PMID- 9186050
TI  - Developmental patterning and evolution of the mammalian viscerocranium: genetic
      insights into comparative morphology.
AB  - The vertebrate cranium is generally classified into the neurocranium and the
      viscerocranium. The latter is derived from the neural crest and so is the
      prechordal portion of the neurocranium. A view we favor considers the prechordal
      neurocranium as the premandibular component of the viscerocranium, and the
      vertebrate skull to consist of the neural crest-derived viscerocranium and the
      mesodermal neurocranium. Of these developmental units, only the viscerocranium
      appears to have completely segmented metamerical organization. The Hox code which
      is known to function in specification of the viscerocranium does not extend
      rostrally into the mandibular and premandibular segments. By genetic manipulation
      of rostrally expressed non-Hox homeobox genes, the patterning mechanism of the
      head is now demonstrated to be more complicated than isomorphic registration of
      the Hox code to pharyngeal arches. The phenotype by haplo-insufficiency of Otx2
      gene, in particular, implies the premandibular cranium shares a common
      specification mechanism with the mandibular arch. Our interpretation of the
      metamerical plan of the viscerocranium offers a new scheme of molecular codes
      associated with the vertebrate head evolution.

PMID- 9186051
TI  - Spatial regulation of floating head expression in the developing notochord.
AB  - The zebrafish homeobox gene floating head (flh) is essential for notochord
      development and is one of the earliest genes to be expressed in notochord
      precursors. To understand how flh is regulated during notochord development, we
      compared the wild-type flh expression pattern to that in embryos mutant for flh
      and no tail (ntl), the zebrafish homologue of Brachyury. In the early gastrula,
      the pattern of flh expression is not affected in either flh or ntl mutants,
      implying that the initial establishment of a gastrula notochord domain is
      independent of the function of these genes. However, flh RNA is expressed at
      lower levels in flh mutants suggesting that flh positively regulates its own
      expression. During gastrulation, flh mutants show an abrupt loss of flh
      expression in cells which have involuted and entered the hypoblast, while the
      rest of the expression pattern appears normal, thus flh+ function is specifically
      required to maintain flh expression in hypoblast cells. The anterior-most part of
      the notochord rudiment differentially maintains flh expression in both wild types
      and flh mutant embryos, suggesting that there is unique regulation of flh in this
      region of the developing notochord. In ntl mutants the spatial pattern of flh
      expression is altered as early as the late gastrula stage, becoming broad and
      diffuse. We hypothesize that ntl+ is required for the proper convergence
      movements of flh-expressing cells.

PMID- 9186052
TI  - Novel Eph-family receptor tyrosine kinase is widely expressed in the developing
      zebrafish nervous system.
AB  - In a search for novel tyrosine kinases involved in vertebrate development, we
      have isolated cDNAs corresponding to three distinct members of the Eph-family of
      receptor tyrosine kinases. Whole mount RNA in situ hybridization analysis showed
      all three genes were most abundantly expressed in the developing nervous system.
      zek1 (zebrafish Eph-like kinase1) encodes a 981 amino acid polypeptide closely
      related to the murine Sek1 and Bsk receptors. Cos-1 cells transfected with zek1
      produce a 141 kilodalton tyrosine phosphorylated protein which is recognized by
      antibodies raised against two predicted Zek1 peptides. These antibodies also
      recognized a protein of the same apparent molecular weight in lysates from
      zebrafish embryos and adults. Widespread expression of zek1 in the developing
      brain and neural tube suggested a generalized function of the Zek1 receptor in
      neuronal cell ontogeny.

PMID- 9186053
TI  - Differential expression of PSA-NCAM and HNK-1 epitopes in the developing cardiac
      conduction system of the chick.
AB  - Although the critical role of the His-Purkinje system (HPS) in the propagation of
      cardiac action potentials from the atria to the ventricular myocardium in the
      mature heart is well appreciated, its functional and anatomical development are
      not well understood. The embryonic heart begins beating early in development
      devoid of a mature conduction system, and the HPS cannot be identified by
      conventional histochemical analysis until the seventh embryonic day of chicken
      development. Although many biochemical markers have been found that apparently
      identify HPS precursors, little is known about how these biochemical markers
      function in the maturation of the cardiac conduction system. Using
      immunohistological techniques, we demonstrated that the maturation of the HPS may
      be observed by the expression of two distinct populations of conduction system
      precursors, identified by the expression of cell surface carbohydrates PSA-NCAM
      (PSA) and HNK-1, both of which are known to participate in cell-cell and cell
      substrate interactions in the development of the nervous system. By stage 25, PSA
      was detected in ventricular trabeculae and the interventricular septum (IVS) in a
      pattern that resembles bundle branches and Purkinje fibers. Beginning at stage
      28, HNK-1 epitope expression in the IVS was observed in myocardium just superior
      to the PSA-positive bundles in a pattern that resembles the common His bundle.
      This junctional region was also positive for atrial myosin heavy chain (alpha
      MHC), another marker for the HPS. These data suggest that a complex, coordinated
      process of biochemical and morphological change governs the development of the
      cardiac conduction system.

PMID- 9186054
TI  - Xenopus LIM motif-containing protein kinase, Xlimk1, is expressed in the
      developing head structure of the embryo.
AB  - The LIM double zinc finger motif locates in several developmentally functioning
      and cytoskeletal proteins, and is considered to act as a specific motif for
      protein-protein interactions. LIM kinase (LIMK) is a novel protein kinase
      containing two LIM motifs at the N-terminal, the function of which has yet to be
      clearly defined. In this study, we cloned a cDNA encoding Xenopus counterpart of
      human LIMK1 gene by RT-PCR mediated cloning, and designated in Xlimk1. Xlimk1 is
      highly homologous to mammalian LIMK1 in each structural domain, particularly in
      LIM and protein kinase domains. In Northern blot analysis, two distinct Xlimk1
      transcripts of 9.0 Kb and 3.7 Kb were present in early cleavage stages of the
      embryo. Both mRNA species were subsequently decreased at the gastrula stages. The
      9.0 Kb of Xlimk1 mRNA again appeared in late neurula stage, then the expression
      level gradually increased in later stages of the embryo. Whole-mount in situ
      hybridization analysis showed the localization of Xlimk1 transcripts in the
      animal half of the blastula embryo. In post-neurula stages, specific signals for
      Xlimk1 were predominant in the anterior (head) region of the embryo, including
      developing brain, hyoid and branchial arches, and anlagen of sensory organs.
      These results indicate that Xlimk1 may play an important role in neural
      development and formation of anterior (head) structures in the Xenopus embryo.

PMID- 9186055
TI  - Fibroblast growth factors 2 and 4 stimulate migration of mouse embryonic limb
      myogenic cells.
AB  - Fibroblast growth factors (FGFs) are believed to be vital for limb outgrowth and
      patterning during embryonic development. Although the effect of FGFs on the
      formation of the skeletal elements has been studied in detail, their effect on
      the development of the limb musculature is still uncertain. In this study, we
      used Blindwell chemotactic chambers to examine the effect of FGF-2 and FGF-4 on
      the motility of myogenic cells obtained from the proximal region of the day 11.5
      mouse forelimbs. The limb myogenic cells were found to be chemotactically
      attracted to FGF-2 and FGF-4 at 10-50 ng/ml. Both FGFs increased myogenic cell
      migration in a dose-dependent manner, with maximal responses attained at 1-50
      ng/ml for FGF-2 and at 10 ng/ml for FGF-4; however, FGF-2 was found to be a more
      potent chemoattractant than FGF-4. It was possible to inhibit the myogenic cells'
      response to FGF-2 and FGF-4 by the addition of the appropriate neutralizing
      antibody. The effects of FGF-2 on cell migration were further investigated by
      loading this cytokine into Affi-Gel blue beads and transplanting them into day
      11.5 forelimb buds. The results showed that FGF-2 attracted DiI-labelled proximal
      cells to migrate toward the implanted beads and that the migration was more
      extensive than that observed in the absence of FGF-2. A checkerboard assay was
      performed in which various concentrations of FGF-2 and FGF-4 were introduced to
      both the upper and lower wells of the Blindwell chambers. The results indicated
      that both FGF isoforms can stimulate chemokinesis as well as chemotaxis in
      myogenic cells. In addition, the effect of FGF-2 at 0.1-10 ng/ml stimulated a
      significant increase in the number of myocytes expressing sarcomeric myosin on
      examination after 48 hr in culture, but the effect of FGF-4 was negligible at all
      concentrations analyzed; however, both FGF-2 and FGF-4 inhibited myocyte fusion
      compared with the spontaneous fusion observed in control cultures. Finally, we
      used in situ hybridization and immunohistochemical techniques to determine the
      distribution of myogenic cells and FGF-2 protein in the day 11.5 mouse forelimbs.

PMID- 9186056
TI  - Maid: a maternally transcribed novel gene encoding a potential negative regulator
      of bHLH proteins in the mouse egg and zygote.
AB  - We isolated an abundant novel cDNA SSEC-8 from a subtraction cDNA library
      enriched for maternal transcripts that are still present in the mouse 2 cell
      stage embryo. This gene is evolutionarily conserved and maps to the distal region
      of mouse chromosome 2. The deduced polypeptide sequence of the encoded protein
      contains a conserved helix-loop-helix (HLH) motif without a basic DNA binding
      domain, suggesting that it functions as a negative regulator of basic (b) HLH
      transcription factors. Gel mobility shift assays show that in vitro translated
      protein prevents the E12/MyoD bHLH dimer from binding to DNA. Also, transient
      overexpression of this protein in C2C12 cells reduced the transcription of a CAT
      reporter regulated by an E12/MyoD driven enhancer. The 3'-UTR contains consensus
      sequences of cytoplasmic polyadenylation elements (CPE's), and the length of its
      poly (A) tail changes during oocyte maturation, indicating that its expression is
      controlled by timely activation of translation. This new gene, Maid, models the
      translational and transcriptional regulation of gene expression during the
      transition from gamete to embryo.

PMID- 9186057
TI  - Shh expression in developing and regenerating limb buds of Xenopus laevis.
AB  - The zone of polarizing activity (ZPA) is a specialized region involved in the
      antero-posterior (A-P) axis formation in chick and mouse limb buds. The existence
      of ZPA in the posterior margin is suggested in Xenopus hindlimb buds because 180
      degree rotation of the distal limb tip induces the supernumerary limb. In this
      study, we investigated the expression of Sonic hedgehog (shh), a molecular marker
      for ZPA, in Xenopus developing limb buds and regenerating blastemas by whole
      mount in situ hybridization. Although shh was expressed in the posterior margin
      of the limb bud like in chicks, its expression domain did not correspond to the
      ZPA map of Xenopus hindlimb buds. shh expression was distant from the ZPA at
      stage 53 in particular. To clarify the difference between the shh expression
      domain and ZPA, we examined shh expression in 180 degree rotated limb buds. As a
      result, ectopic shh expression was newly induced in the proximal region to its
      original expression domain. These results suggest that ZPA is accompanied by shh
      expression as in chick limb buds. Furthermore we examined shh expression in
      regenerating blastemas. shh was reexpressed in the posterior margin of the
      blastema. This result supports the possibility that ZPA also exists in the
      regenerating blastema.

PMID- 9186058
TI  - MRF4 can substitute for myogenin during early stages of myogenesis.
AB  - MRF4, myogenin, MyoD, and Myf-5 are the four members of the basic helix-loop
      helix family of muscle-specific regulatory factors (MRFs). We examined whether
      MRF4 could substitute for myogenin in vivo by determining if the myofiber- and
      MRF4-deficient phenotype of myogenin (-/-) mice could be rescued by a myogenin
      promoter-MRF4 transgene. When the transgene was expressed at a physiological
      level in myogenin-deficient fetuses, we found that expression of the endogenous
      MRF4 gene was restored to normal levels, whereas MyoD levels were unchanged.
      Thus, MRF4 can participate in a positive autoregulatory loop and can substitute
      for myogenin to activate its own promoter. Myogenin-deficient fetuses that
      expressed the transgene also had more myosin, more and larger myofibers, and a
      more normal ribcage morphology than myogenin-deficient littermates without the
      transgene. The transgene failed, however, to restore normal numbers of myofibers
      or viability to myogenin-deficient mice, because the approximately 1.6 kb
      myogenin promoter fragment was not expressed in most late-forming myofibers.
      These results demonstrate that MRF4 is able to substitute for myogenin to
      activate MRF4 expression and promote myofiber formation during the early stages
      of myogenesis.

PMID- 9186059
TI  - Backfoot is a novel homeobox gene expressed in the mesenchyme of developing hind
      limb.
AB  - Homeobox genes play important roles in pattern formation during development.
      Here, we report the cloning and temporal and spatial expression patterns of a
      novel homeobox gene Backfoot (BFT for the human gene, and Bft for the mouse
      gene), whose expression reveals an early molecular distinction between forelimb
      and hind limb. BFT was identified as a sequence-specific DNA-binding protein. In
      addition to the homeodomain, it shares a carboxyl-terminal peptide motif with
      other paired-like homeodomain proteins. Northern hybridization analysis of RNAs
      from human tissues revealed that human BFT is highly expressed in adult skeletal
      muscle and bladder. During midgestation embryogenesis, mouse Bft is expressed in
      the developing hind limb buds, mandibular arches, and Rathke's pouch. The
      expression of Bft begins prior to the appearance of hind limb buds in mesenchyme
      but is never observed in forelimbs. At later stages of limb development, the
      expression is progressively restricted to perichondrial regions, most likely in
      tendons and ligaments. The timing and pattern of expression suggest that Bft
      plays multiple roles in hind limb patterning, branchial arch development, and
      pituitary development. Bft is likely identical to a mouse gene, Ptx1, that was
      recently isolated by Lamonerie et al. ([1996] Genes Dev. 10:1284-1295) and that
      has been suggested to play a role in pituitary development.

PMID- 9186060
TI  - Antihypertensive therapy: how to evaluate the benefits.
AB  - For more than 30 years, the benefits of antihypertensive therapy have been
      assessed in randomized trials that monitor cardiovascular events. Even greater
      benefits can result if prevention of (1) congestive heart failure, (2) left
      ventricular hypertrophy, and (3) progression to more severe hypertension is taken
      into consideration. However, quantifying the benefits in order to calculate the
      cost-effectiveness of treatment is not easy. Taking absolute risk and benefit as
      the only guide to treatment decisions may result in limiting therapy only to
      elderly hypertensive patients and hypertensive patients with complications.
      Furthermore, randomized trials, of which the duration is necessarily short, are
      likely to underestimate treatment benefits. An alternative to such an approach is
      the actuarial approach: treatment benefits are calculated from the actuarial data
      showing the reduction in life expectancy associated with any given blood pressure
      increase. The cost of antihypertensive therapy per year of life gained calculated
      in this way is much lower than the cost calculated from randomized trials. In an
      uncertain area such as that of cost-effectiveness evaluation, it is important
      that both approaches are taken into consideration by physicians, patients,
      politicians, and officers of national health systems.

PMID- 9186061
TI  - The calcium antagonist controversy: the emerging importance of drug formulation
      as a determinant of risk.
AB  - Calcium antagonists are one of the widely available classes of antihypertensive
      agents. Their broad appeal is attributable to several features, including their
      efficacy, their beneficial characteristics such as metabolic neutrality, and the
      occurrence of relatively few nuisance-type side effects. Despite these
      attributes, a number of retrospective analyses have suggested that calcium
      antagonists may be detrimental and may both promote adverse cardiovascular events
      and increase the risk of cancer by interfering with cellular apoptosis. On the
      basis of this and other retrospective analyses, Furberg and Psaty (Am J Hypertens
      1996; 9: 122-125) have proposed that the use of calcium antagonists as first-line
      antihypertensive agents should be discontinued. I have previously countered these
      allegations and have suggested that they are not relevant to the newer calcium
      antagonist formulations in current use. It is not widely appreciated that
      different formulations of the same chemical moiety can produce markedly different
      hemodynamic and neurohormonal effects, due to differences in the rate of drug
      delivery into the systemic circulation. During chronic treatment with
      dihydropyridine calcium antagonists, major fluctuations in blood pressure (rapid
      onset and offset of antihypertensive effects) during the dosing interval may
      occur for drugs and formulations that are short acting. In contrast, slow-release
      formulations of otherwise rapidly absorbed dihydropyridines achieve a more
      gradual and sustained antihypertensive effect. It is probable that newer calcium
      antagonist formulations that are truly once daily and do not provoke intermittent
      sympathetic activation or a cardioacceleratory response will not promote adverse
      cardiovascular events.

PMID- 9186062
TI  - Is the calcium antagonist debate having an effect on clinical practice?
AB  - The controversies over the long-term safety of calcium antagonists have produced
      considerable debate in both the medical and lay press. However, there are no data
      on whether this debate has influenced routine clinical practice. As most drugs in
      the Western healthcare systems are prescribed by primary care physicians, the aim
      of this study was to explore the perceptions of primary care clinicians with
      regard to their prescribing of calcium antagonists. Semistructured interviews of
      primary care physicians were performed in four countries, the Netherlands,
      Germany, Spain, and the United States. These interviews investigated the levels
      of awareness of primary care physicians about the recent calcium antagonist
      debate, and whether the debate had influenced their personal prescribing
      practice. Physicians were also asked if they considered the duration of calcium
      antagonist action to be clinically important. The results indicated that, despite
      the recent controversy over the safety of calcium antagonists, primary care
      physicians were largely unaware of the debate and had made no significant
      alterations to their routine practice. Although 15% cited potential nonspecified
      side effects, only 14% recalled a specific connection between the use of calcium
      antagonists and adverse cardiac events or higher mortality. Knowledge of adverse
      risks was significantly greater among physicians in the United States than among
      physicians in the other 3 countries. Finally, 90% of respondents were aware of
      the differences in duration of action of various calcium antagonists; of these,
      90% felt that this had clinical significance.

PMID- 9186063
TI  - Effects of calcium antagonists on insulin sensitivity and other metabolic
      parameters.
AB  - The antihypertensive efficacy of calcium antagonists appears to be comparable to
      that of oral diuretics when used as monotherapy. Peripheral vascular dilation
      appears to be the principal mechanism of the long-term blood pressure-lowering
      effects of calcium antagonists. The calcium antagonists appear to have beneficial
      effects with respect to maintenance of renal blood flow and glomerular filtration
      rate. Metabolic abnormalities associated with diuretic and beta-blocker
      antihypertensive therapy, such as hypokalemia, hypercalcemia, hyperuricemia,
      lipid changes, and hyperglycemia, are generally not observed with calcium
      antagonists.

PMID- 9186064
TI  - What does nisoldipine coat core (CC) add to current therapy that is clinically
      meaningful?
AB  - Nisoldipine coat core (CC) is a long-acting dihydropyridine with good
      tolerability. Ambulatory blood pressure measurements in a large, South African
      multicenter trial show that it has an excellent trough:peak ratio, and that it
      reduces the early morning rise in blood pressure without any tachycardia.
      Nisoldipine CC is an effective antihypertensive agent in both black and nonblack
      South African ethnic groups. In another South African study, regression of left
      ventricular hypertrophy was achieved in black patients with severe diastolic
      hypertension. Safety issues are discussed against the background of the testing
      of this drug in postinfarct left ventricular dysfunction.

PMID- 9186065
TI  - Use of calcium antagonists in patients with ischemic heart disease and systemic
      hypertension.
AB  - Ischemic heart disease (IHD) and systemic hypertension commonly coexist in a
      large number of patients, and the presence of hypertension is a risk factor for
      worsening IHD. A monotherapy that would effectively treat both is thus an
      attractive idea, and calcium antagonists have been evaluated in this role.
      Calcium antagonists exert therapeutic effects through a combination of actions,
      including systemic and peripheral vasodilation, negative inotropy, and reduced
      nodal conduction. In randomized, double-blind clinical trials, verapamil compares
      favorably with propranolol in the alleviation of angina and hypertension. Both
      diltiazem and nifedipine, as well as long-acting diltiazem, are also effective in
      treating the combined condition. In addition, each of these drugs enhances
      exercise tolerance and favors compliance with calcium antagonist therapy. Recent
      questions regarding the safety of this class of drug have tempered the enthusiasm
      for their use as first-line therapy in cardiovascular disease. In particular,
      short-acting dihydropyridine derivatives, including nifedipine and isradipine,
      may increase cardiovascular morbidity and mortality because of reflex sympathetic
      stimulation. The results of appropriately controlled, prospective clinical trials
      will provide more definitive conclusions. For now, we must be cautious in the use
      of calcium antagonist monotherapy for combined IHD and hypertension.

PMID- 9186066
TI  - Cardiac effects of calcium antagonists in systemic hypertension.
AB  - The calcium antagonists are a class of heterogeneous drugs, with a wide spectrum
      of direct and indirect cardiac effects that vary a great deal from one drug to
      another and depend upon formulation and duration of action. Calcium antagonists
      act by decreasing total peripheral resistance to lower arterial pressure. As a
      consequence, reflex tachycardia, increased cardiac output, and increased plasma
      catecholamine and plasma renin activity are commonly seen, particularly with the
      initial dose and with short-acting dihydropyridines. The abrupt vasodilation can
      paradoxically elicit angina and even acute myocardial infarction. These
      hemodynamic and neuroendocrine changes are less pronounced with the long-acting
      formulations. Most calcium antagonists diminish automaticity of the sinus node,
      slow conduction in the atrioventricular node, and have little, if any, effect on
      the automaticity of the myocytes. The dihydropyridines generally have less effect
      on automaticity and cardiac conduction than nondihydropyridines. The negative
      inotropic effect is most profound with nondihydropyridines and is greatly reduced
      or absent with newer dihydropyridines, such as isradipine, felodipine,
      amlodipine, and nisoldipine. Long-acting calcium antagonists generally improve
      myocardial oxygenation by unloading the heart, increasing coronary blood flow,
      and reducing myocardial oxygen consumption. Thus, calcium antagonists have a
      variety of beneficial effects in patients with hypertensive heart disease: they
      reduce left ventricular hypertrophy and its sequelae, such as ventricular
      dysrhythmias, impaired filling and contractility, and myocardial ischemia.
      Ongoing studies should provide a more conclusive answer regarding the efficacy
      and safety of calcium antagonists.

PMID- 9186067
TI  - IgA nephropathy databank: development of a system for management of renal biopsy
      acquired data.

PMID- 9186068
TI  - Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244
      cases.
AB  - IgA nephropathy (IgAN) may present with a wide variety of histologic patterns on
      renal biopsy, ranging from a minimal lesion to a diffuse proliferative
      glomerulonephritis (GN). The histologic features of 244 cases of IgAN (not
      including Schonlein-Hanoch nephritis) diagnosed between 1980 and 1994 were
      reviewed, and each case was subclassified using the following, relatively simple
      histologic classification scheme: subclass I (39 cases): minimal or no mesangial
      hypercellularity, without glomerular sclerosis; subclass II (18 cases): focal and
      segmental glomerular sclerosis without active cellular proliferation; subclass
      III (110 cases): focal proliferative GN; and subclass IV (42 cases): diffuse
      proliferative GN; and subclass V (35 cases): any biopsy showing > or = 40%
      globally sclerotic glomeruli and/or > or = 40% estimated cortical tubular atrophy
      or loss. Subsequent analysis of renal survival in 109 patients who underwent
      biopsy before or during 1992 for whom such data were available showed a strong,
      statistically significant correlation between histologic subclass and renal
      survival, with an order I, II (greatest survival) > III > IV, V. Crescents were a
      significant negative prognostic indicator for renal survival in subclass III (but
      not in subclass IV), and interstitial expansion was a negative prognostic
      indicator in subclasses III and IV, although the statistical significance of
      these were not maintained after controlling for serum creatinine at the time of
      biopsy. The presence of peripheral glomerular capillary deposits
      ultrastructurally had no prognostic significance. With respect to clinical
      presentation, hypertension (systolic blood pressure > or = 130 mm Hg and
      diastolic blood pressure > or = 90 mm Hg) and proteinuria of > or = 2.0 g/24 hr
      were significant negative prognostic indicators for renal survival, even when
      controlling for serum creatinine at the time of renal biopsy. The presence of
      gross hematuria correlated significantly with increased renal survival by
      univariate analysis, but not when controlling for serum creatinine at the time of
      renal biopsy. The findings of this study confirm the wide variety of clinical and
      histopathologic presentations of IgAN, and indicate the utility of the proposed
      histologic classification schema in assessing a patient's likelihood of
      ultimately developing end-stage renal disease.

PMID- 9186069
TI  - Glomerulointerstitial interaction of adhesion molecules in IgA nephropathy and
      membranoproliferative glomerulonephritis.
AB  - The expression of two adhesion molecules, ICAM1 (CD54) and ICAM3 (CD50),
      infiltrating cells positive for their ligand, LFA1 (CD11a), and the markers of
      total leukocytes (CD45), T cells (CD3), granulocytes/monocytes (CD15), and
      macrophages (CD68) in renal interstitium were examined by an indirect
      immunoperoxidase method. The study was longitudinally performed on repeat renal
      biopsy specimens from 69 patients with two different proliferative
      glomerulonephritides: 43 with IgA nephropathy (IgAN) and 26 with
      membranoproliferative glomerulonephritis (MPGN). Interstitial ICAM1 (iICAM1) was
      mainly expressed on endothelium of peritubular venules and sometimes on tubular
      epithelium, and interstitial ICAM3 (iICAM3) on infiltrating immune cells. In
      IgAN, iICAM1 was significantly correlated with glomerular infiltration of LFA1+
      cells (gLFA1) and CD68+ cells (gCD68) (r = 0.478/0.500; P < 0.0001) as well as
      CD3+ cells (gCD3) (r = 0.402; P < 0.002). In MPGN, iICAM1 was significantly
      correlated only with gCD68 (r = 0.382; P < 0.05). In both diseases, iICAM1 and
      iICAM3 were significantly correlated with interstitial infiltration of LFA1+
      cells (iLFA1) and CD68+ cells (iCD68) (r = 0.616 to 0.815; P < 0.0001) and with
      interstitial infiltration of CD3+ cells (iCD3) (r = 0.474 to 0.816; P < 0.01).
      The iICAM3 was also significantly correlated with interstitial CD45+ cells
      (iCD45) (r = 0.672 in IgAN and 0.769 in MPGN; P < 0.00001). Interstitial
      infiltration of these immune cells was significantly correlated with the
      histologic parameters indicating renal injury, such as the index of glomerular
      lesion and the percent interstitial volume (r = 0.410 to 692; P < 0.05).
      Longitudinal analysis revealed that the parameters described above showed
      corresponding change with each other at the follow-up biopsy. These findings
      suggest that the glomeruler infiltration of T cells and macrophages influences
      the ICAM1/ICAM3 expression of the interstitial cells, especially In IgAN, and
      that ICAM1/LFA1 and ICAM3/LFA1 interactions contribute to the persistent
      infiltration of the interstitium by immune cells in both diseases.

PMID- 9186070
TI  - Improvement in adequacy of delivered dialysis for adult in-center hemodialysis
      patients in the United States, 1993 to 1995.
AB  - The objective of this review is to describe the adequacy of delivered dialysis
      provided to in-center hemodialysis patients in the United States and to compare
      the findings with published guidelines. The medical records of random samples of
      6,138, 6,919, and 6,861 patients in hemodialysis facilities were studied from all
      Medicare-eligible adult in-center hemodialysis patients alive on December 31,
      1993, 1994, and 1995, respectively. The main clinical measure used was the urea
      reduction ratio (URR), the mean of which was 0.63 in 1993, 0.64 in 1994, and 0.66
      in 1995. The proportion of patients with URR > or = 0.65, as recommended by the
      Renal Physicians Association and a National Institutes of Health Consensus
      Development Conference Statement, increased from 43% in 1993 to 49% in 1994 and
      59% in 1995. In each of these 3 years, women were more likely than men to have a
      URR > or = 0.65 (1993: 54% v 31%, odds ratio 2.6; 1994: 61% v 38%, odds ratio
      2.5; and 1995: 70% v 50%, odds ratio 24), as were older patients (65+ years)
      compared with younger patients (18 to 44 years) (1993: 47% v 37%, odds ratio 1.4;
      1994: 54% v 45%, odds ratio 1.5; and 1995: 65% v 53%, odds ratio 1.6) and white
      patients compared with black patients (1993: 46% v 36%, odds ratio 1.5; 1994: 53%
      v 43%, odds ratio 1.5; and 1995: 63% v 54%, odds ratio 1.4). There was also
      substantial geographic variation in the proportion of patients receiving
      hemodialysis with a URR > or = 0.65. In conclusion, marked differences existed in
      1993, 1994, and 1995 between observed practice and consensus guidelines for the
      delivery of adequate dialysis. Nevertheless, notable improvement occurred during
      this time period. A system to monitor further improvements in hemodialysis care
      in the United States is in place.

PMID- 9186071
TI  - Hyperparathyroidism in the hemodialysis population: a survey of 612 patients.
AB  - There are no epidemiologic studies documenting the prevalence of
      hyperparathyroidism in the US hemodialysis population. We looked at a random
      sample of 612 hemodialysis patients enrolled in 10 outpatient dialysis units in
      Mississippi. Fifty percent of the patients surveyed had an intact serum
      parathyroid hormone (PTH) level more than three times normal (mean, 622 pg/mL).
      Another 25% had a less than normal PTH level (mean, 33 pg/mL), suggesting
      adynamic bone disease. Abnormal serum calcium was also common. Seventeen percent
      of patients were hypocalcemic and 14% were hypercalcemic. These high point
      prevalences occurred despite widespread use of calcium supplements and/or vitamin
      D (used in 90% of the patients surveyed). Black patients tended to have a lower
      serum calcium and higher PTH level than white patients. We also found that
      diabetic patients are less likely to have an elevated PTH level than nondiabetic
      patients. Elevated serum phosphorus was the most important factor correlating
      with the development of secondary hyperparathyroidism. Causes of inadequate
      control of hyperparathyroidism in this population require further study.

PMID- 9186072
TI  - Effect of recombinant human erythropoietin on lymphocyte phenotyping and
      phagocyte activity in hemodialysis patients.
AB  - The effect of recombinant human erythropoietin (rHmEPO) on lymphocytic
      phenotyping as well as on the phagocyte activity of polymorphonuclear cells and
      monocytes was evaluated in 16 patients on maintenance hemodialysis. The mean age
      of the patients was 38.2 +/- 16.2 years. There were seven men and nine women. All
      patients were started on 50 U/kg of rHmEPO intravenously three times per week,
      and the dosage was increased gradually to achieve target haemoglobin of 12 g/dL.
      Predialysis blood samples were taken monthly for 3 months, and phagocyte
      respiratory burst as well as lymphocyte subsets were studied. Healthy blood
      donors were taken as controls. By 3 months of rHmEPO treatment, there was no
      significant increase in total T and B cells, but there was a significant increase
      in both CD4 (P < 0.001) and CD8 (P < 0.005): however, there was no significant
      change in the CD4/CD8 ratio. There was significant reduction in the natural
      killer cells (P < 0.005). The phagocyte activity studies showed a significant
      increase in the respiratory burst in whole blood (P < 0.001) and opsonized
      zymosan (P < 0.001) as well as improvement in the suppressed polymorphonuclear
      cell and monocyte activity by uremia. Phagocytosis studied by yeast uptake showed
      significant improvement from the pretreatment suppressed phagocytes to normal
      activity posttreatment. In conclusion, treatment with rHmEPO increases CD4 and
      CD8 cell counts without affecting the CD4/CD8 ratio, decreases the natural killer
      cells, and improves the impaired phagocyte activity in hemodialysis patients.

PMID- 9186073
TI  - Interleukin-8 expression in patients after renal transplantation.
AB  - Cellular invasion and cytokine release are important steps in the initiation of
      rejection. We studied the release of interleukin-8 (IL-8), a potent
      proinflammatory and chemotactic cytokine, and its prognostic significance in
      predicting rejection after renal transplantation. Serum and urine samples were
      analyzed with an IL-8-specific sandwich enzyme-linked immunosorbent assay. Biopsy
      tissue specimens (n = 20) were snap-frozen and examined with immunohistochemistry
      using two monoclonal antibodies against human IL-8 (4G9 and 2A8). Serum IL-8
      measurements were of no value in predicting rejection due to low sensitivity
      (24%). In 45 biopsy-proven acute rejections (< 2 months after transplantation),
      urinary IL-8 concentrations were elevated in 62% (298 +/- 54 pg/mL; P < 0.01),
      preceding clinical diagnosis of rejection. After treatment, the IL-8
      concentration in urine decreased back to normal (33 +/- 4 pg/mL; P < 0.01). The
      highest urinary IL-8 concentrations were seen in patients with biopsy-proven
      rejection in combination with acute tubular necrosis (610 +/- 150 pg/mL). This
      finding was independent of renal function and urinary volume. Only three of 15
      rejection episodes in patients more than 2 months after transplantation showed an
      elevated IL-8 concentration in urine (94 +/- 60 pg/mL). In 10 of 23 patients with
      infection, a significant increase of IL-8 in urine was observed as well (157 +/-
      67 pg/mL; P < 0.05). IL-8-positive staining was found within interstitial
      mononuclear cells of all biopsy specimens showing rejection. Additionally, the
      antibody 4G9 stained arteriolar smooth muscle and tubular cells. Interestingly, a
      few IL-8-positive cells were present in two donor kidneys before transplantation
      was performed; control tissue was negative. Further investigations are necessary
      to determine the clinical value of urinary IL-8 determinations in the diagnosis
      of rejection and to evaluate the role of IL-8 in the pathogenesis of acute
      allograft rejection.

PMID- 9186074
TI  - Unemployment in inner-city renal transplant recipients: predictive and
      sociodemographic factors.
AB  - Studies of dialysis patients report unemployment rates of 60% to 75%; however, it
      is generally believed that following transplantation, improvement in well-being
      and removal of time constraints imposed by the dialytic regimen afford
      improvement in employment status. We studied 58 stable renal transplant recipient
      attending an outpatient transplant clinic by questionnaire, administered
      anonymously. Only 25 (43%) of the patients were currently employed. Employed and
      unemployed patients did not differ when compared for age, gender, race, cause of
      renal disease, type of transplant or prior dialysis, time on dialysis or time
      since transplantation, years of education, or prestige score or classification
      ("blue collar" v "white collar") of prior job. In the employed group, 24 (96%)
      patients had worked before developing kidney disease compared with 23 (70%)
      patients in the unemployed group (P < 0.05). While on dialysis, 19 (79%) of the
      employed patients continued working compared with 10 (30%) of the unemployed
      patients (P < 0.005). Major reasons for discontinuing work after starting
      dialysis for both groups were subjective illness (feeling too sick, 51%),
      followed by interference of the dialysis regimen with time necessary for work
      (32%). Only 15% of the previously employed patients did not work after
      transplantation because of feeling too sick. By multiple logistic regression, the
      strongest predictors of employment posttransplant were being more than 1 year
      posttransplant (odds ratio, 2.35; 95% confidence interval, 1.01 to 5.5) and
      having been employed before transplantation (odds ratio, 3.79; 95% confidence
      interval, 1.60 to 9.02). Over half of the unemployed patients (20 [61%])
      expressed interest in job training. Eighty percent to 90% of patients in both
      groups were insured by Medicare, with the second greatest number insured by
      Medicaid. Of the 15 unemployed patients insured by Medicaid, 67% reported that
      their decision not to work was related to fear of losing Medicaid benefits
      because they could not afford medications without it. Despite no difference in
      actual type of insurance carried, 17 (51%) of the unemployed patients believed
      their health insurance coverage was inadequate compared with four (12%) of the
      employed patients (P = 0.005, chi-squared test). Unemployment remains a
      significant problem for our population of inner-city renal transplant recipients.
      Attention to job retention or retraining during the early renal disease and
      dialysis therapy period may promote better rehabilitation following
      transplantation. However, for this population, with limited employment
      opportunities, removal of disincentives to work, including loss of Insurance and
      Inability to pay for medications, will be necessary before we can provide optimal
      rehabilitation for renal transplant recipients from all social strata.

PMID- 9186075
TI  - Cross-sectional study of quality of life and symptoms in chronic renal disease
      patients: the Modification of Diet in Renal Disease Study.
AB  - The purposes of this study were to measure health-related quality of life in the
      Modification of Diet in Renal Disease clinical trial; correlate quality of life
      measures with demographic, medical, and laboratory variables; and compare quality
      of life in various chronic diseases. The 1,284 patients enrolled in the baseline
      period of the Modification of Diet in Renal Disease study who completed at least
      one measurement of quality of life or symptoms served as the subjects of this
      study. The Quality of Well-Being (QWB) scale, which was a general health-related
      quality of life index, the Symptom Checklist-90R (SCL-90R), which provided a
      global measure of mental health, and the Patient Symptom Form, which assessed the
      frequency of symptoms specific to this population, were used as measurements. The
      mean +/- SD QWB score was 0.74 +/- 0.09. Using multivariate analysis, there was a
      significant negative correlation between the overall QWB score and age and female
      gender, and a significant positive correlation between the QWB and level of
      education, income, and glomerular filtration rate (GFR). For the SCL-90R
      subscores, the mean normalized Global Symptom Index was 49.7 +/- 9.6, the
      Positive Symptom Total was 47.9 +/- 10.4, and the mean Positive Symptom Distress
      Index was 51.3 +/- 12.6. Using multivariate analysis, significant inverse
      relationships were seen between each of the SCL-90R subscores and income, serum
      albumin level, and GFR. The most commonly reported medical symptoms in this
      cohort included tiring easily, weakness, lack of pep or energy, difficulty
      sleeping, and abdominal bloating or gas. Symptoms in which the severity index
      score had a negative correlation with GFR included tiring easily, weakness, lack
      of pep and energy, muscle cramps, easy bruising or bleeding, bad taste in mouth,
      and hiccoughs. In conclusions, patients with moderate to advanced renal
      insufficiency have a reduced quality of life and an increased frequency and
      severity of both symptoms and psychological distress, with the magnitude of these
      changes negatively correlated with GFR.

PMID- 9186077
TI  - Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent
      diabetes mellitus and renal failure.
AB  - To test the hypothesis that renal failure has no effect on the pharmacokinetics
      of glyburide, five subjects with non-insulin-dependent diabetes mellitus (NIDDM)
      and end-stage renal disease requiring hemodialysis, and four NIDDM subjects with
      normal renal function were studied. On days 0, 1, and 15, subjects consumed 33
      carbohydrate grams, and glucose, insulin, and C-peptide were measured for 4
      hours. On day 1, subjects received 3 mg glyburide and measured plasma
      concentrations for 48 hours. On day 3, multiple dosing on 3 mg glyburide daily
      began. On day 15, plasma concentrations were measured for 48 hours. The
      pharmacokinetics and pharmacodynamics of glyburide, glucose, insulin, and C
      peptide were determined as well as daily fasting blood glucose. Glucose area
      under the curve (AUC) and daily fasting glucose levels did not change in either
      controls or hemodialysis subjects. The mean serum glyburide blood levels and
      pharmacokinetics did not differ after initial or chronic glyburide administration
      in NIDDM subjects with end-stage renal disease treated with hemodialysis compared
      with controls. Glyburide half-life averaged 3.3 hours in control subjects and 5.0
      hours in hemodialysis subjects. Hemodialysis subjects had increased C-peptide and
      insulin AUC with chronic dosing. Renal failure does not affect the
      pharmacokinetics of 3.0 mg oral glyburide.

PMID- 9186078
TI  - Myofibroblasts and arteriolar sclerosis in human diabetic nephropathy.
AB  - We examined the biopsy specimens of 62 patients with diabetic nephropathy to
      establish whether the myofibroblast (MF) has a role in progressive interstitial
      fibrosis and to ascertain whether a relationship existed between MF activity and
      severity of arteriolosclerosis. MF were identified by morphology and alpha smooth
      muscle actin (alpha SMA) immunostaining. Analysis of vascular injury was
      performed by counting the number of interstitial arterioles after staining
      endothelial cells with von Willebrand factor (VWF) antibody. Arteriosclerosis was
      quantified by using a computer-aided image analyzer to measure the arteriolar
      wall surface and total arteriolar surface area, and the ratio of wall to total
      surface area was expressed as the index of arteriosclerosis (IA). Fractional area
      of interstitium (IFA), alpha SMA, and collagen III (Coll III) were quantitated by
      point counting. Results were related to structural and functional parameters
      using rank correlation coefficients. There was a strong correlation between IFA
      and Coll III staining (r = 0.83; P < 0.001). The alpha SMA staining correlated
      with IFA (r = 0.56; P < 0.001) and Coll III (r = 0.47; P < 0.001), and there were
      significant correlations between alpha SMA and total urinary protein (r = 0.47; P
      < 0.001), renal function (plasma creatinine) at time of biopsy (r = 0.51; P <
      0.001), and the percent change in plasma creatinine after 4 years (delta Cr) (r =
      0.37; P = 0.01). The IA correlated significantly with Coll III (r = 0.29; P =
      0.02), glomerular filtration rate (GFR) (r = 0.39; P = 0.008), and creatinine (r
      = 0.33; P = 0.01), but no correlation was observed between alpha SMA and IA (r =
      0.16; P = 0.23) or IA and delta Cr (r = -0.04; P = 0.6). Strong correlations
      could be shown between arteriolar density, IFA (r = 0.75; P < 0.001), alpha SMA
      (r = -0.36; P = 0.034), and Coll III (r = -0.66; P < 0.0001). The MF appears to
      have a significant role in the progression of diabetic nephropathy. Ischemia
      secondary to arteriosclerosis may contribute to interstitial fibrosis through
      fibroblast modulation into MF.

PMID- 9186076
TI  - Racial differences in the renal response to blood pressure lowering during
      chronic angiotensin-converting enzyme inhibition: a prospective double-blind
      randomized comparison of fosinopril and lisinopril in older hypertensive patients
      with chronic renal insufficiency.
AB  - This study was undertaken to compare the effects of chronic angiotensin
      converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics
      in older black and nonblack hypertensive patients with chronic renal
      insufficiency. A multicenter, placebo lead-in double-blind, parallel group study
      was performed to compare the antihypertensive efficacy and renal hemodynamic
      response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n =
      13) over a 22-week period. The study goal was to lower diastolic blood pressure
      (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure
      goal was not achieved. At outpatient clinics at university medical centers, 27
      older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male,
      eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20
      to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP,
      glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean
      systolic blood pressure (SBP) and DBP decreased significantly and to a similar
      extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was 
      13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P <
      0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P <
      0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, 
      12 to -21). GFR and RPF did not change significantly in either group. BP was
      significantly reduced and to a similar extent in blacks and nonblacks: for
      blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at
      22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP
      at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12
      +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three
      nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal
      of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either
      racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR
      decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26
      to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta
      GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35
      +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR
      or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with
      fosinopril and lisinopril alone or in combination with furosemide lowers BP in
      older blacks and nonblacks with hypertension and chronic renal insufficiency.
      Racial differences in the renal hemodynamic response to chronic ACE inhibition
      were noted and appear to be independent of diuretic use and the magnitude of BP
      lowering.

PMID- 9186079
TI  - Effect of lipoproteins on cultured human mesangial cells.
AB  - It was recently reported that low-density lipoprotein (LDL) promotes mesangial
      cell proliferation, and oxidized LDL is cytotoxic for mesangial cells. However,
      there have been few studies about the effects of other lipoproteins on mesangial
      cells. Accordingly, we investigated the effect of various lipoproteins on
      cultured human mesangial cells using 3H-thymidine (3H-TdR) incorporation and cell
      counting assays. We also investigated the levels of several cytokines in
      mesangial cell culture supernatants after stimulation by the lipoproteins.
      Addition of very-low-density lipoprotein (VLDL) at concentrations up to 100
      micrograms/mL, intermediate-density lipoprotein (IDL) at up to 50 micrograms/mL,
      and LDL at up to 50 micrograms/mL induced the proliferation of cultured human
      mesangial cells, whereas cell growth was inhibited at higher concentrations.
      Oxidized LDL caused a concentration-dependent decrease of 3H-TdR incorporation.
      High-density lipoprotein (HDL) had no proliferative effective effect at any
      concentration. Exposure to VLDL, IDL, LDL, or a high concentration of HDL
      enhanced the secretion of interleukin-6, platelet-derived growth factor, and
      transforming growth factor-beta by mesangial cells, whereas tumor necrosis factor
      alpha secretion was stimulated by oxidized LDL. These finding indicate that
      triglyceride (TG)-rich lipoproteins (VLDL and IDL) promote mesangial cell
      proliferation as well as LDL, whereas oxidized LDL has the reverse effect. These
      effects of lipoproteins may be related to modulation of various cytokines.
      Accordingly, TG-rich lipoproteins, LDL, and oxidized LDL may be involved in
      mesangial cell proliferation and injury in patients with mesangial proliferative
      glomerulonephritis.

PMID- 9186080
TI  - A 41-year-old woman with protein S deficiency and diffuse proliferative lupus
      nephritis: is protein S deficiency associated with a hyperinflammatory response?
AB  - A 41-year-old woman with complete protein S (PS) deficiency who developed diffuse
      proliferative lupus nephritis is reported. She was referred to our hospital with
      nephrotic syndrome and thrombocytopenia. Her medical history included
      colorectostomy and amputation of the extremities because of repeated thrombotic
      episodes during her teens without any evidence of systemic lupus erythematosus.
      The diagnosis of PS deficiency was made from the patient's clinical course,
      undetectable serum PS in either the active or inactive form, normal protein C
      activity, and no evidence of the antiphospholipid syndrome. However, there was no
      definitive family history. A depressed level of complements and a positive
      antinuclear acid antibody suggested a diagnosis of systemic lupus erythematosus.
      The patient had a rapidly progressive course and died of disseminated
      intravascular coagulation. An autopsy showed generalized thrombotic lesions and
      diffuse proliferative lupus nephritis on both ordinal light and immunoperoxidase
      microscopy. Our observations suggest that PS-deficient patients may have a
      hyperinflammatory response.

PMID- 9186081
TI  - Renal artery stenosis and unilateral focal and segmental glomerulosclerosis.
AB  - Focal and segmental sclerosed lesions in the glomeruli are found in several
      pathological entities and more often are found in the corticomedullary junction
      where renal blood flow and filtration pressure is maximal. Experimental data
      suggest that hyperfiltration injury results in focal and segmental
      glomerulosclerosis (FSGS). In keeping with this concept, malignant hypertension
      is a known cause of nephrotic-range proteinuria and nephrotic syndrome
      pathalobically represented by FSGS. We report a case of unilateral renal artery
      stenosis associated with nephrotic syndrome and FSGS in the contralateral kidney
      only. The kidney with the stenosed renal artery showed normal glomeruli with
      juxtaglomerular hyperplasia, suggesting that protection from hyperfiltration
      injury was provided by the presence of high-grade stenosis. Serum creatinine
      concentration, blood pressure, and proteinuria normalized after aorto-renal
      bypass surgery. This case shows the importance of hemodynamic factors on the
      pathogenesis of secondary FSGS and the progression of renal disease.

PMID- 9186082
TI  - Light chain deposition disease complicating familial Mediterranean fever.
AB  - Familial Mediterranean fever (fMf) is an inherited condition characterized by
      polyserositis and is sometimes complicated by AA renal amyloidosis leading to
      nephrotic syndrome and renal failure. We present a case of a man with fMf who
      presented with rapidly progressive renal failure caused by light chain deposition
      disease. This disease association has not previously been described in the
      medical literature.

PMID- 9186084
TI  - Prognostic indicators of progressive renal disease in IgA nephropathy: emergence
      of a new histologic grading system.

PMID- 9186083
TI  - Primary hyperoxaluria in an adult with renal failure, livedo reticularis,
      retinopathy, and peripheral neuropathy.
AB  - We present the case of a young woman who developed renal failure of unknown
      cause, and after 2 months of maintenance hemodialysis developed livedo
      reticularis, retinopathy, and peripheral sensory neuropathy. The patient was
      subsequently shown to have primary oxalosis type I, a rare autosomal recessive
      error of metabolism characterized by accumulation of calcium oxalate crystals in
      the kidneys, eyes, skin, and other organs. Intravascular obstruction, caused by
      deposition of calcium oxalate crystals in cutaneous arterioles, is thought to be
      responsible for the ischemic livedo reticularis lesions observed in this patient.
      A method is described for measuring serum glycolate by isotope dilution gas
      chromatography-mass spectrometry (GC-MS). An approach to the diagnosis and
      management is also briefly mentioned.

PMID- 9186085
TI  - Hyperkalemia and trimethoprim-sulfamethoxazole.

PMID- 9186086
TI  - An adolescent with relapsing nephrotic syndrome: minimal-change disease versus
      focal-segmental glomerulosclerosis versus C1q nephropathy.

PMID- 9186087
TI  - Regulation of filtration rate by glomerular mesangial cells in health and
      diabetic renal disease.
AB  - The rate of renal filtration is in large part responsible for volume and
      electrolyte balance in an organism. Integral components of the renal glomerulus
      are the mesangial cells (MCs), excitable renal pericytes that regulate the
      glomerular filtration rate by modulating the surface area of the capillaries.
      Similar to vascular smooth muscle, the signal transduction pathways and ion
      selective channels regulating isotonic and isometric contraction of MCs are
      dependent on the voltage-gated Ca influx. During the response to contractile
      agonists, both Cl and nonselective cation channels play critical roles to
      depolarize the membrane potential and activate Ca channels. The relaxation
      pathways involve a negative-feedback mechanism that counteracts mesangial
      contraction by regulating voltage-dependent Ca signaling. Part of the feedback
      response involves the activation of plasmalemmal K channels, which hyperpolarize
      the membrane potential and inhibit voltage-gated Ca entry. This calcium- and
      voltage-activated feedback K (BKCa) channel shares biophysical, pharmacologic,
      and molecular properties with the BKCa channels identified in brain and muscle,
      and with the sio gene product as expressed in Xenopus laevis oocytes. Systemic
      hormones, such as atrial natriuretic peptide, and paracrine factors, such as
      nitric oxide (NO), use guanosine 3',5'-cyclic monophosphate (GMP) as a second
      messenger and enhance the gain in this feedback system by decreasing the voltage
      and Ca activation thresholds for BKCa. Diabetes mellitus is often associated with
      high rates of glomerular filtration, mesangial expansion, and secretory
      abnormalities of the basement membrane. NO-mediated increases in negative
      feedback regulation of mesangial tone may attribute, in part, to the pathology of
      hyperfiltration. Stimulation of inducible nitric oxide synthetase in glomerular
      MCs by inflammatory cytokines is a possible positive-feedback pathway that
      contributes to further glomerular destruction. In addition, high ambient glucose,
      through modulation of BKCa activity, facilitates MC relaxation and thus
      propagates hyperfiltration. Since cellular arachidonic acid is metabolically
      linked to extracellular glucose, this fatty acid is a possible mediator of the
      pathologic actions of hyperglycemia. Clarification of the signal transduction
      pathways and ionic mechanisms regulating the normal and dysfunctional tones of
      MCs is essential for rational clinical management of glomerular disease and
      critical to understanding fluid and electrolyte homeostasis.

PMID- 9186088
TI  - Spontaneous tendon ruptures in patients on chronic dialysis.

PMID- 9186089
TI  - Combination analgesic involvement in the pathogenesis of analgesic nephropathy.

PMID- 9186090
TI  - Differences in total carbon dioxide results are not due to different assay
      techniques.

PMID- 9186091
TI  - Eye manifestations of congenital toxoplasmosis.
AB  - PURPOSE: To determine the natural history of treated and untreated congenital
      toxoplasmosis and impact of this infection on vision. METHODS: In this
      prospective, longitudinal study, 76 newborns were treated with pyrimethamine and
      sulfadiazine for approximately one year, and 18 individuals not treated during
      their first year of life entered the study after age 1 year (historical
      patients). RESULTS: Chorioretinal scars were the most common eye finding in all
      patients and were most common in the periphery (58% of treated and 82% of
      historical patients). Macular scars were present in 54% of the treated patients;
      41% were bilateral. Macular scars were present in 76% of the historical patients;
      23% were bilateral. Visual acuity in the presence of macular lesions ranged from
      20/20 to 20/400. Of the patients followed up from the newborn period and treated,
      29% had bilateral visual impairment, with visual acuity for the best eye of less
      than 20/40. Causes for this visual impairment in eyes with quiescent lesions
      included macular scars, dragging of the macula secondary to a peripheral lesion,
      retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were
      recurrences in both treated (13%, 7/54) and previously untreated historical
      patients (44%, 8/18). The total, median, and range of years of follow-up during
      which recurrences were observed were, for treated patients, 189 years (total),
      five years (median) and three to ten years (range) and, for historical, untreated
      patients, 160 years (total), 11 years (median), and three to 24 years (range).
      New lesions occurred in previously normal retinas and also contiguous to older
      scars. Active lesions appeared to become quiescent within ten to 14 days after
      beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with
      congenital toxoplasmosis have substantial retinal damage at birth and consequent
      loss of vision. Nonetheless, vision may be remarkably good in the presence of
      large macular scars. Active lesions become quiescent with treatment.

PMID- 9186092
TI  - Clinical assessment of long-term safety and efficacy of a widely implanted
      silicone intraocular lens material.
AB  - PURPOSE: To summarize the long-term safety and efficacy, in a large series of
      patients, of intraocular lenses made from a second-generation silicone material
      (AMO SLM-2/UV) widely used as an intraocular lens material. METHODS: This was a
      prospective study of adult patients who received posterior-chamber intraocular
      lenses with an optic composed of a high-index-of-refraction, ultraviolet-light
      absorbing silicone (AMO SLM-2/UV). In 501 patients, clinical data through 3 years
      postoperative are presented. Postoperative measurements included spectacle
      corrected visual acuity, occurrence of postoperative sight-threatening or lens
      related complications, and adverse reactions. Results were compared with the
      standards established by the US Food and Drug Administration (FDA) for
      polymethylmethacrylate lenses. RESULTS: At 1 year, 95.2% (496/521) of all
      patients in group I achieved corrected visual acuity of 20/40 or better. This
      compared well with the standard reported for polymethylmethacrylate lenses (88%,
      2,521/2,864). At 3 years, 94.3% (347/368) of best-case patients achieved
      corrected visual acuity of 20/40 or better. The rate of sight-threatening
      complications reported at the final postoperative examination at 3 years was 2.0%
      (10/501). The rate of Nd:YAG capsulotomy was 27.5% (138/501) through 3 years.
      CONCLUSION: Lenses made of the SLM-2/UV silicone material demonstrated safe and
      effective performance through long-term follow-up at a level equal to or better
      than established standards for polymethylmethacrylate lenses.

PMID- 9186093
TI  - Secondary posterior chamber intraocular lens implantation in pediatric patients.
AB  - PURPOSE: To report results of secondary posterior chamber intraocular lens (IOL)
      implantation in previously aphakic pediatric patients. METHODS: In 19 pediatric
      patients, 19 aphakic eyes (11 after infantile and eight after traumatic cataract
      surgery) received secondary sulcus-fixated posterior chamber IOL implants.
      RESULTS: Visual acuity of 20/40 or better was achieved with IOL implantation and
      overrefraction in three of 11 infantile (27%) and six of eight traumatic cataract
      patients (mean follow-ups, 18.1 months [range, 8 to 29 months] and 18.0 months
      [range, 6 to 28 months]), respectively. Eighteen of 19 patients (95%)
      demonstrated postoperative vision equal to or better than preoperative levels; 15
      of 19 patients (79%) showed improved vision after IOL implantation. The mean +/-
      SD difference between actual and predicted postoperative refraction at 1 month
      was -0.97 +/- 0.96 diopter. Average refractive error at last examination was 
      0.40 +/- 2.43 diopters. Amblyopia therapy was performed in 14 patients. One IOL
      required repositioning 8 months postoperatively. Strabismus was present in 14
      patients before and 13 patients after IOL implantation, requiring surgery in four
      patients. CONCLUSIONS: Secondary IOL implantation can be performed successfully
      in carefully selected pediatric patients. Visual acuity results are better in
      eyes with a history of traumatic cataract and are influenced by patient
      compliance. The short-term risks of the procedure appear no greater than those of
      primary IOL implantation, and complications resemble those seen in adults.

PMID- 9186094
TI  - Reproducibility of digital image analysis for measuring corneal haze after myopic
      photorefractive keratectomy.
AB  - PURPOSE: To evaluate the usefulness of digital image analysis for quantifying
      corneal haze by determining the reproducibility of its measurements at the
      corneal plane. METHODS: In a prospective study, 20 randomly selected eyes that
      had undergone myopic photorefractive keratectomy were photographed focusing the
      slit beam on their anterior corneal surface. Each photograph was examined using
      computer image analysis techniques that detect the edge of the reticular pattern
      of the image. Quantification of the difference between two areas, treated and
      adjacent untreated cornea, each containing 3,750 pixels with a resolution of 256
      gray levels, was performed. Intra-analyzer variation was determined by evaluating
      the photographs obtained by two analyzers under standard conditions on four
      separate visits. Interanalyzer variation was calculated using one measurement and
      the mean of the four measurements. RESULTS: The pooled standard deviation of the
      measurements for the analyzers was 0.63 and 0.62 gray levels (coefficient of
      variation, 4.1% and 3.3%). An association between less severe haze measurements
      and higher reproducibility scores was found (r = .42; P = .007). The mean
      interanalyzer variation was smaller for the average of four measurements, 0.55 +/
      0.37 gray levels, than for one measurement, 0.94 +/- 0.73 gray levels (P =
      .014). CONCLUSIONS: Good reproducibility for haze measurements by digital image
      analysis of the differences between the treated and adjacent untreated corneal
      areas was obtained. When the average of four measurements was used instead of a
      single measurement, interanalyzer reproducibility increased significantly. This
      new technique may be used to quantify and analyze corneal haze after myopic
      photorefractive keratectomy.

PMID- 9186095
TI  - Laser-induced fluorescence during photorefractive keratectomy: a method for
      controlling epithelial removal.
AB  - PURPOSE: Laser-induced fluorescence is generated during ablation of corneal
      tissue with the argon-fluoride 193-nm excimer laser. To investigate possible
      changes in laser-induced fluorescence spectra emitted during the transition
      between epithelium and stroma, we developed a system using an intensified charge
      coupled device to achieve fast per-pulse temporal resolution of laser-induced
      fluorescence. METHODS: Freshly enucleated human cadaver eyes were subjected to
      193-nm excimer laser keratectomy. During the procedure, laser-induced
      fluorescence was measured using an intensified charge-coupled device. Changes in
      laser-induced fluorescence were detected and used to control epithelial removal.
      Depth of ablation was determined histologically. RESULTS: The 193-nm excimer
      laser pulses induced both visible and ultraviolet fluorescence from corneal
      epithelium and stroma. In each layer two peaks predominated, one at 405 nm and
      the other at 346 nm. There was a rapid threefold reduction in the 346-nm
      ultraviolet peak at the transition from epithelium to stroma. CONCLUSIONS: By
      monitoring changes in laser-induced fluorescence at the epithelial-stromal
      interface, the clinician may be able to control corneal epithelial removal more
      precisely and reproducibly before performing photorefractive ablation.

PMID- 9186097
TI  - Clinical experience with the Ahmed Glaucoma Valve implant in eyes with prior or
      concurrent penetrating keratoplasties.
AB  - PURPOSE: To evaluate the Ahmed Glaucoma Valve implant, an aqueous shunting device
      with a unidirectional valve mechanism, in eyes with concurrent or prior
      penetrating keratoplasties. METHODS: Thirty-one eyes of 31 consecutive patients
      had placement of an Ahmed Glaucoma Valve implant. Median patient age was 65.1
      years (range, 17.2 to 103.4 years). The main outcome measure was time after
      surgery without failure. Success was defined as no additional glaucoma surgeries
      or devastating visual complications, no new corneal graft failure, an intraocular
      pressure greater than or equal to 5 mm Hg on the last two follow-up examinations,
      and reduction in intraocular pressure. For eyes with preoperative intraocular
      pressure greater than 22 mm Hg, an average intraocular pressure of less than 22
      mm Hg on the last two follow-up examinations was required. For eyes with
      preoperative intraocular pressure of less than 22 mm Hg, an intraocular pressure
      lowered by at least 20% from preoperative values was required. RESULTS:
      Cumulative probabilities of success at 12 and 20 months (mean +/- SD) were 75.4%
      +/- 8.2% and 51.5% +/- 11.4%, respectively. Eleven of 31 eyes were failures. The
      risk of failure in eyes with prior infectious keratitis or keratouveitis was
      estimated to be 5.8 times greater than that associated with eyes that underwent
      penetrating keratoplasties for other reasons (P = .009). CONCLUSIONS: Twelve- and
      20-month success rates of the implant in eyes with prior or concurrent
      penetrating keratoplasties were comparable to those of other drainage devices.
      Eyes with prior infectious keratitis or keratouveitis were at increased risk of
      failure.

PMID- 9186096
TI  - Trabeculectomy with intraoperative 5-fluorouracil vs mitomycin C.
AB  - PURPOSE: To compare the effectiveness of intraoperative 5-fluorouracil (5-FU) and
      mitomycin C used adjunctively with trabeculectomy in a black West African
      population. METHODS: Eighty-five consecutive eyes of 85 black patients undergoing
      primary trabeculectomy for open-angle glaucoma were prospectively randomly
      assigned to receive either 5-FU (50 mg/ml for 5 minutes) or mitomycin C (0.5
      mg/ml for 3 1/2 minutes) intraoperatively by soaked sponge. RESULTS: Of the 81
      eyes with at least a 3-month postoperative follow-up, 41 of 44 (93.2%) in the
      mitomycin C group and 27 of 37 (73.0%) in the 5-FU group had a final intraocular
      pressure of less than 21 mm Hg (P = .01). Twenty-eight of 44 eyes (63.6%) in the
      mitomycin C group and 18 of 37 (51.4%) in the 5-FU group had a final intraocular
      pressure of less than 15 mm Hg (P = .26). Mean postoperative intraocular pressure
      was 13.7 mm Hg in the mitomycin C group and 16.3 mm Hg in the 5-FU group (P =
      .05). There were no differences between the two groups in mean age, preoperative
      intraocular pressure, postoperative visual acuity, and complications. Mean follow
      up was 10.0 +/- 4.41 months (range, 4 to 19 months). CONCLUSIONS: The adjunctive
      use of mitomycin C with trabeculectomy is equally safe and more efficacious
      compared to 5-FU in this West African population. Use of mitomycin C in this
      study was not associated with a statistically significantly greater proportion of
      patients achieving low intraocular pressure (less than 15 mm Hg) compared to 5
      FU.

PMID- 9186098
TI  - The sensitivity and specificity of nerve fiber layer measurements in glaucoma as
      determined with scanning laser polarimetry.
AB  - PURPOSE: To determine the sensitivity and specificity for detecting glaucoma by
      scanning laser polarimetry and to assess the relation between nerve fiber layer
      (NFL) measurements and visual field indices. METHODS: The peripapillary NFL was
      divided into four segments: superior, inferior, temporal, and nasal. The mean
      polarimetric NFL for each segment was calculated out of six selected areas of 256
      pixels each. Ratios relative to the nasal segment were determined for the
      superior and inferior segments. With the use of previously obtained normograms
      for polarimetric NFL readings, the sensitivity of scanning laser polarimetry was
      assessed in 200 glaucomatous eyes (155 subjects). The specificity was assessed in
      a normal population of 150 eyes (150 subjects). The relation between hemifield
      polarimetric NFL and visual field indices was assessed by linear regression
      analysis. RESULTS: The sensitivity of scanning laser polarimetry was 96% and the
      specificity was 93%. The correlation between NFL parameters and visual field
      indices ranged from -0.18 to +0.26. The amount of variation by the linear
      regression model ranged from 3% to 6%. CONCLUSIONS: Although quantitative
      measurements of the NFL with scanning laser polarimetry relate poorly to visual
      field indices, the technique seems to be promising for screening populations for
      glaucoma. Whether measurements of the NFL with scanning laser polarimetry are
      also sensitive enough to detect change over time requires further study.

PMID- 9186100
TI  - White dot fovea.
AB  - PURPOSE: To describe a newly identified clinical entity tentatively named white
      dot fovea. METHODS: We examined by scanning laser ophthalmoscopy 58 eyes of 30
      patients (mean age, 64 years) who had white dots in the fovea (anatomically
      defined as the foveola) simulating macular hole. In addition, the retinal
      surfaces of 30 autopsy eyes from donors aged 70 years or older were observed by
      scanning electron microscopy. RESULTS: White dot fovea was bilateral in 28 of 30
      patients (93%). It was characterized by the presence of numerous white dots on
      the foveal surface distributed either diffusely or along the foveal margin,
      forming a gray ring. There was no subjective symptom or visual disturbance. The
      condition was best seen by a scanning laser ophthalmoscope using argon blue laser
      as the light source. The white dots numbered from 100 to 300 per eye. Each dot
      was approximately 5 microns in diameter. Scanning electron microscopy showed
      foveal granules simulating the white dots in five of 30 autopsy eyes (17%). The
      granules had multiple protrusions with cilia-like structures resembling glial
      cells. This glia-like structure seemed to be a counterpart of clinically observed
      white dot fovea. CONCLUSION: White dot fovea is a new, frequent, and apparently
      innocuous clinical entity. It merits due attention in the differential diagnosis
      of macular holes.

PMID- 9186099
TI  - The association of HLA-DR15 and intermediate uveitis.
AB  - PURPOSE: To evaluate the association between human leukocyte antigen (HLA-DR15)
      specificity and intermediate uveitis. METHODS: Eighteen patients diagnosed with
      intermediate uveitis underwent HLA-DR15 serotyping. Additionally, DNA-based
      phenotyping for a specific HLA-DR15 allele was performed in four patients. The
      clinical features of HLA-DR15-positive intermediate uveitis were compared with
      those of HLA-DR15-negative intermediate uveitis. RESULTS: Thirteen of 18 patients
      (72%) were positive for HLA-DR15. The frequency of the HLA-DR15 specificity in
      intermediate uveitis patients was significantly higher than in the control
      subjects (relative risk, 6.36; P < .001). Each of four patients tested carried
      the specific allele, DR beta 1*1501, which has been associated with multiple
      sclerosis. In the HLA-DR15-positive group were four patients (31%) with
      coexisting multiple sclerosis or optic neuritis, one patient with coexisting
      narcolepsy, and three patients (23%) with a family history of multiple sclerosis.
      Retinal periphlebitis, especially if bilateral, was a frequent ophthalmoscopic
      finding in HLA-DR15-positive intermediate uveitis. CONCLUSIONS: This study
      identifies a significant association between intermediate uveitis and the HLA
      DR15 specificity. Patients who are HLA-DR15-positive and have intermediate
      uveitis may have systemic findings of another HLA-DR15-related disorder.
      Intermediate uveitis may belong to a constellation of HLA-DR15-related disorders,
      which includes multiple sclerosis, optic neuritis, and narcolepsy.

PMID- 9186101
TI  - Visual acuity and macular hole size after unsuccessful macular hole closure.
AB  - PURPOSE: To evaluate the visual acuity, change in macular hole size, and change
      in subretinal fluid cuff size after unsuccessful macular hole closure. METHODS:
      Forty-two consecutive eyes with macular hole and unsuccessful surgery for macular
      hole were studied. Preoperative and postoperative best-corrected visual acuities
      were tested according to the Early Treatment Diabetic Retinopathy Study (ETDRS)
      protocol, and changes were compared. Preoperative and postoperative fundus
      photographs were analyzed on a photograph documenter for changes in diameter of
      the macular hole and surrounding subretinal fluid cuff. RESULTS: Mean visual
      acuity decreased from 20/133 preoperatively to 20/154 postoperatively (mean loss,
      0.79 ETDRS line). Mean diameter of the macular hole enlarged 22%; mean diameter
      of the visible surrounding subretinal fluid cuff enlarged 36%. A decrease in best
      corrected visual acuity postoperatively was correlated with better preoperative
      visual acuity, earlier macular hole stage, and shorter duration. Enlargement in
      the diameter of the macular hole and fluid cuff did not correlate with better
      preoperative best-corrected visual acuity, earlier macular hole stage, or shorter
      duration. In 23 eyes that had failed previous surgery, macular hole surgery was
      anatomically successful in 17 (65%) (mean improvement, 3.7 ETDRS lines; mean best
      corrected final visual acuity, 20/74). CONCLUSION: After macular hole surgery,
      anatomically unsuccessful closure of the hole correlates with small enlargements
      in the diameter of the macular hole and its surrounding subretinal fluid cuff,
      and with a slight decrease in visual acuity. Macular hole closure after repeat
      surgery improves visual acuity outcome in the majority of retreated eyes.

PMID- 9186102
TI  - Perfusion of the subfoveal choriocapillaris affects visual recovery after
      submacular surgery in presumed ocular histoplasmosis syndrome.
AB  - PURPOSE: To determine the relationship between the visual result and perfusion of
      the subfoveal choriocapillaris after surgical excision of subfoveal
      neovascularization in presumed ocular histoplasmosis syndrome. METHODS: We
      reviewed the records of 38 eyes of 37 patients with gradable postoperative
      fluorescein angiograms and color photographs after surgical excision of a
      subfoveal neovascular membrane in presumed ocular histoplasmosis syndrome. The
      postoperative photographs and fluorescein angiograms were graded in a masked
      fashion for the presence of perfusion of the subfoveal choriocapillaris. We used
      preoperative and postoperative best-corrected visual acuities to determine the
      correlation between postoperative perfusion of the subfoveal choriocapillaris and
      both final visual acuity and visual improvement after surgery. RESULTS: After
      surgery, the subfoveal choriocapillaris was perfused in 24 of the 38 eyes (63%)
      and nonperfused in 14 (37%). Best-corrected visual acuity improved by at least 2
      Snellen lines in 17 of the 24 perfused eyes (71%) and two of the 14 nonperfused
      eyes (14%) (P = .0089). Best-corrected visual acuity of 20/100 or better was
      achieved in 18 of the perfused eyes (75%) and four nonperfused eyes (29%) (P =
      .0076). CONCLUSION: Both final visual acuity and improvement in visual acuity
      were correlated with postoperative perfusion of the subfoveal choriocapillaris in
      patients with presumed occular histoplasmosis syndrome. Development of techniques
      to maintain or reestablish perfusion of the subfoveal choriocapillaris after
      surgery may improve visual outcome in these eyes.

PMID- 9186103
TI  - Pattern-reversal visual evoked potentials in patients with epiretinal membrane.
AB  - PURPOSE: To determine the extent of pattern-reversal visual evoked potential
      parameter alteration by epiretinal membranes and to investigate the use of
      pattern-reversal visual evoked potential in the estimation of macular function in
      eyes with epiretinal membrane and in the fellow eyes. METHODS: In both eyes of
      162 patients with epiretinal membrane, 92 of primary and 70 of secondary origin,
      pattern-reversal visual evoked potentials were recorded. Check sizes of 17', 10',
      and 7' (minutes of arc) were used. Parameters investigated were N80 and P100
      latencies and P100 amplitude. RESULTS: No significant difference was detected
      between eyes with epiretinal membrane of primary and secondary origin regarding
      visual acuity and the pattern-reversal visual evoked potential parameters for the
      different check sizes. Compared with the fellow eyes, the eyes with epiretinal
      membrane had a significantly reduced visual acuity, prolonged N80 and P100
      latencies, and a reduced P100 amplitude for the different check sizes. Compared
      with a separate control group (N = 20) with patients 50 to 59 years old, eyes
      with epiretinal membrane (N = 9) showed the same features as in the total group,
      but only for the 17' and 10' check sizes. The fellow eyes (N = 9) showed a
      significant reduction of the P100 amplitude (P < .05) for the pattern sizes of
      17' and 10', but no difference in visual acuity or pattern-reversal visual evoked
      potential latency was found. CONCLUSIONS: In eyes with epiretinal membrane,
      pattern-reversal visual evoked potential latencies are prolonged, and amplitude
      is reduced. Relationships between clinical parameters and pattern-reversal visual
      evoked potential parameters require further study.

PMID- 9186104
TI  - Incidence of nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: Nonarteritic anterior ischemic optic neuropathy is the most common acute
      optic nerve disease of adults over age 50 years. This study determined the
      incidence of acute nonarteritic anterior ischemic optic neuropathy in the
      circumscribed population of Olmsted County, Minnesota. METHODS: This was a
      retrospective study of the incidence of acute nonarteritic anterior ischemic
      optic neuropathy between 1981 and 1990. The Rochester Epidemiology Project
      medical records linkage system facilitates identification of the medical records
      of virtually all Olmsted County residents with a given diagnosis. All cases of
      acute nonarteritic anterior ischemic optic neuropathy that fulfilled certain
      inclusion and exclusion criteria were identified. RESULTS: Twenty-two cases in 21
      patients (11 men and 10 women) were recorded. The crude annual incidence rate was
      10.3 per 100,000 individuals (95% confidence interval [CI] = 5.1 to 18.4). When
      adjusted to the age and sex distribution of the 1990 United States white
      population, the incidence rate was 10.2 per 100,000 (95% CI = 6.5 to 15.6). At
      diagnosis, the median age was 72 years, mean visual acuity was 20/200 in the
      affected eye, and the most common visual field defect was an altitudinal deficit
      (10 cases). CONCLUSIONS: Although results of this small study should be
      interpreted cautiously, extrapolation of our findings to the United States white
      population indicates that nearly 5,700 new cases of acute nonarteritic anterior
      ischemic optic neuropathy may be expected to occur each year in this group.

PMID- 9186105
TI  - Ophthalmologic findings in patients with ataxia.
AB  - PURPOSE: To determine the frequency and spectrum of ophthalmologic findings in a
      large, heterogeneous group of patients with ataxia. METHODS: Medical records of
      184 patients from a university-based ataxia clinic were retrospectively reviewed.
      Patients were classified as having Friedreich's ataxia, spinocerebellar
      degeneration, cerebellar degeneration, familial or sporadic olivo-pontocerebellar
      atrophy, multisystem atrophy, spastic ataxia, myoclonic ataxia, or other
      diagnoses such as mitochondrial myopathy. All had complete ophthalmologic
      examinations, and 107 underwent electro-oculography. RESULTS: Among 184 patients
      with ataxia, diplopia was present in 52 (28%), best-corrected visual acuity was
      decreased in 29 (16%), and oscillopsia was present in 10 (5%). Diplopia was
      usually caused by an intermittent, small-angle heterotropia. The reduction in
      best-corrected visual acuity varied from mild to profound and was caused by optic
      atrophy, retinal degeneration, or both. Optic atrophy was present most frequently
      in spastic ataxia (five of 22 patients) and myoclonic ataxia (two of eight
      patients), followed by Friedreich's ataxia (three of 26 patients). Retinal
      degeneration and ophthalmoplegia were most characteristically associated with
      familial olivopontocerebellar atrophy and mitochondrial myopathy. Laboratory
      testing of ocular motility showed frequent abnormalities in all groups. Fixation
      instability was most characteristic of Friedreich's ataxia, whereas saccadic
      slowing was noticeably absent from patients with purely cerebellar degenerations.
      CONCLUSIONS: The ataxias may be associated with visual dysfunction caused by
      retinal degeneration, optic atrophy, oculomotor disturbance, or a combination of
      these.

PMID- 9186107
TI  - The perils of permanent punctal plugs.
AB  - PURPOSE: To describe previously unreported complications associated with
      permanent lacrimal punctal plugs. METHOD: Five oculoplastic practices reviewed
      patients referred to them over the preceding 2 years for permanent lacrimal
      punctal plug complications. RESULTS: In 12 patients, 14 lacrimal punctal plugs
      migrated distally within the lacrimal drainage system, causing symptoms and
      necessitating surgical removal. CONCLUSION: Luxation of permanent punctal plugs
      into the distal lacrimal drainage system can occur, sometimes requiring complex
      surgical intervention.

PMID- 9186108
TI  - Retreatment of decentered excimer photorefractive keratectomy ablations.
AB  - PURPOSE: To present two cases of excimer photorefractive keratectomy decentration
      associated with visual distortion secondary to irregular astigmatism. METHOD:
      Patients were retreated with a repeat photorefractive keratectomy using a
      technique whereby the circle of adherent epithelium overlying the decentered
      ablation served as a mask. RESULTS: After retreatment, there was significant
      improvement in the patients' visual symptoms, decreased astigmatism on
      refraction, and better centration on corneal topography. CONCLUSION: This method
      appears to offer an effective means to treat photorefractive keratectomy ablation
      zone decentration by improving the abnormalities introduced by the initial
      decentration.

PMID- 9186109
TI  - Postoperative retinal ischemia with self-sealing cataract surgery incisions.
AB  - PURPOSE: To report the potential for retinal ischemia caused by high intraocular
      pressure and to suggest a simple test for this condition. METHODS: We measured
      the intraocular pressure and directly examined the optic nerve head in four eyes
      of four patients at the conclusion of cataract surgery. RESULTS: With intraocular
      pressure above 40 mm Hg, elderly patients may abruptly lose the ability to
      perceive microscope illumination. The central retinal artery pulsated at these
      pressures. Light perception returned immediately upon reduction of intraocular
      pressure. CONCLUSION: Testing for light perception at the conclusion of surgery
      can indicate retinal ischemia with loss of light perception, which may occur
      during sealing of the cataract surgical wound.

PMID- 9186110
TI  - Corneal perforation associated with argon laser photocoagulation for a retinal
      tear.
AB  - PURPOSE: To report a corneal perforation during argon laser photocoagulation
      around a retinal tear following pneumatic retinopexy. METHODS: The patient was
      examined and found to have a corneal perforation with pigment in the base of the
      wound. To help explain this phenomenon, we evaluated the ability of argon blue
      green laser to create a corneal perforation in a cadaver eye. RESULTS: In a
      cadaver eye, we induced a corneal perforation with argon laser only when a
      pigmented substance was present on the corneal surface. CONCLUSIONS: We
      hypothesize that pigmented material such as an eyelash or mascara caught between
      the cornea and contact lens interface may have facilitated this rare
      complication. Clinicians should be wary of any pigmented substance on the surface
      of the cornea or ophthalmoscopic lens when performing argon laser
      photocoagulation.

PMID- 9186111
TI  - Acute retinal pigment epitheliitis.
AB  - PURPOSE: To report a patient with acute retinal pigment epitheliitis examined
      less than 24 hours after onset of symptoms. METHOD: One day after the onset of
      blurred vision in her left eye, a 33-year-old woman had a best-corrected visual
      acuity of LE, 20/60 -2. The left eye had classic uniform golden-colored nodules
      in a honeycomb pattern in the foveal retinal pigment epithelium. Intravenous
      fundus fluorescein angiography disclosed staining of the foveal pigment
      epithelium. RESULTS: One month after initial examination, visual acuity was LE,
      20/20, and fine subfoveal pigmentary clumping was present. CONCLUSION: The
      pigmentary maculopathy of acute retinal pigment epitheliitis may be nonspecific,
      resulting from more than one type of primary foveal inflammation.

PMID- 9186112
TI  - Acute progressive multifocal Best's disease in a 61-year-old man.
AB  - PURPOSE: To report acute progressive multifocal Best's disease in patients in
      their seventh decade. METHOD: We report one such case. RESULTS: We examined a 61
      year-old man with strikingly symmetric, 1-disk diameter serous retinal
      detachments involving each fovea. Fluorescein angiography was unremarkable, with
      no dye leakage. Electrophysiologic testing confirmed the diagnosis. Visual acuity
      decreased, and within 1 month, the size and number of lesions rapidly increased.
      Three months later, the lesions quickly evolved to the classic vitelliform stage.
      CONCLUSION: This well-documented case expands the spectrum of findings in
      multifocal Best's disease.

PMID- 9186113
TI  - Toxoplasmic retinochoroiditis: new insights provided by indocyanine green
      angiography.
AB  - PURPOSE: To analyze features of indocyanine green angiography associated with
      recurrent toxoplasmic retinochoroiditis. METHODS: Indocyanine green angiography
      was performed according to a standard protocol and correlated with clinical signs
      and fluorescein angiography in 12 eyes of 12 consecutive patients with recurrent
      toxoplasmic retinochoroiditis. RESULTS: In 10 of 12 eyes with recurrent
      toxoplasmic retinochoroiditis, indocyanine green angiography showed multiple
      satellite dark dots not seen on fluorescein angiography or clinical examination
      of the fundus. CONCLUSION: Indocyanine green angiography shows that recurrent
      toxoplasmic retinochoroiditis is more widespread than clinically visible lesions
      indicate. Indocyanine green angiography is useful in assessing the extent of
      involvement of recurrent toxoplasmic retinochoroiditis and the evolution of
      lesions and might also provide insights into the pathophysiology of the disease.

PMID- 9186114
TI  - Penicillin-resistant Streptococcus pneumoniae endophthalmitis.
AB  - PURPOSE: To report a case of trabeculectomy-associated endophthalmitis caused by
      penicillin-resistant Streptococcus pneumoniae. METHOD: Case report. RESULTS: The
      patient developed endophthalmitis 1 month after an uncomplicated trabeculectomy
      for primary open-angle glaucoma. Vitreous cultures grew abundant, highly
      penicillin-resistant S pneumoniae. Despite aggressive treatment with vitrectomy
      and intravitreal injections of vancomycin hydrochloride and amikacin sulfate, the
      patient had a poor visual outcome. CONCLUSION: Penicillin-resistant S pneumoniae
      can cause endophthalmitis after trabeculectomy.

PMID- 9186116
TI  - Chiasmal optic neuritis in Lyme disease.
AB  - PURPOSE: To report Lyme disease as the cause of chiasmal optic neuritis in a 10
      year-old girl. METHODS: The patient underwent ophthalmologic, laboratory, and
      imaging examinations. RESULTS: The patient's history and clinical course were
      consistent with Lyme disease. Laboratory studies disclosed increased serum Lyme
      immunoglobulin G titer, which improved after antibiotic treatment. CONCLUSION:
      Lyme disease should be considered in the differential diagnosis of chiasmal optic
      neuritis.

PMID- 9186115
TI  - Exogenous Neisseria meningitidis endophthalmitis.
AB  - PURPOSE: To report a case of Neisseria meningitidis endophthalmitis in
      association with a leaking filtering bleb and to consider antibiotic prophylaxis
      of those people with whom the patient had contact. METHOD: We treated an 81-year
      old man who had a chronic, leaking filtering bleb and who developed exogenous N
      meningitidis endophthalmitis. RESULT: N meningitidis endophthalmitis was
      controlled with antibiotic therapy. Antibiotic prophylaxis for those with whom
      the patient had contact was not recommended. CONCLUSION: In this case, the N
      meningitidis strain was not considered invasive because the bacteria apparently
      entered the eye through a leaky filtering bleb and not through the bloodstream.
      Recovery of noninvasive N meningitidis does not require prophylaxis for patient
      contacts. In cases of endogenous or idiopathic N meningitidis endophthalmitis,
      antibiotic prophylaxis of close patient contacts may be warranted.

PMID- 9186117
TI  - Identification of anterior uveal tumor border by transscleral transillumination
      and an ophthalmic endoscope.
AB  - PURPOSE: To report a method for identifying the borders of anterior uveal tumors
      in deeply pigmented eyes. METHOD: The borders of the anterior uveal tumors were
      marked by transscleral transillumination with a fiberoptic light and observed
      from the vitreous cavity using an ophthalmic endoscope. RESULTS: The ophthalmic
      endoscope disclosed a bright orange spot by transscleral transillumination of a
      normal uvea in deeply pigmented eyes. Two anterior uveal melanomas and one
      adenocarcinoma of the nonpigmented ciliary epithelium did not transmit light
      through the tumors. CONCLUSION: With an ophthalmic endoscope and transscleral
      transillumination, the borders of ciliary body tumors can be identified and
      clearly demarcated, even in deeply pigmented eyes.

PMID- 9186118
TI  - Retinal detachment associated with type III retinoblastoma regression after
      cryotherapy and external-beam radiotherapy.
AB  - PURPOSE: To report a child with rhegmatogenous retinal detachment originating
      from a focus of type III retinoblastoma regression after cryotherapy and external
      beam radiation therapy. METHOD: Retinal detachment and multiple retinal holes,
      which were closely associated with the calcified mass of the regressed
      retinoblastoma, were treated with cryotherapy and scleral buckle. RESULTS:
      Positioning the regressed tumor and the retinal holes on the scleral buckle
      closed the holes. Subretinal fluid gradually reabsorbed after surgery, and
      complete retinal reattachment resulted. CONCLUSION: Rhegmatogenous retinal
      detachment is rare in patients with retinoblastoma, and scleral buckle can
      successfully manage such cases. In our patient, the detachment probably resulted
      from retinal necrosis secondary to cryotherapy and external-beam radiation
      therapy.

PMID- 9186119
TI  - Rhabdomyoma of the orbit in a child.
AB  - PURPOSE: To study a case of rhabdomyoma of the orbit in a 16-month-old boy.
      METHOD: The child had progressive right proptosis for 1 month. He underwent a
      computed tomographic scan, which showed an irregular right retrobulbar mass and
      partial resection. RESULTS: Histologic examination disclosed well-differentiated
      striated muscle cells with a mixture of collagen fibers and immature striated
      muscle cells with centrally placed nuclei. The specimen lacked nuclear atypia,
      indicating benign rhabdomyoma of the orbit. During the 1 1/2-year follow-up, the
      patient did not receive additional treatment, and no regrowth occurred.
      CONCLUSION: Rhabdomyoma can occur in the orbit of a child. Because of differences
      in treatment, rhabdomyoma must be distinguished from rhabdomyosarcoma.

PMID- 9186121
TI  - Refractive outcome of radial keratotomy: does the result of the first eye predict
      outcome in the second eye?
AB  - PURPOSE: To present a method of quantifying variability in the outcome of a
      refractive surgical procedure using the SD of the difference between achieved and
      expected refractive changes. We used this method to determine whether the
      refractive outcome of radial keratotomy in a first eye is predictive of outcome
      in the second eye. METHODS: We retrospectively identified patients who underwent
      eight-incision radial keratotomy in the first eye from February 1993 through
      April 1994, with follow-up refraction 2.5 to 5 months postoperatively. This group
      consisted of 129 eyes of 81 patients. Thirty-nine patients had bilateral surgery
      with appropriate follow-up. Achieved refractive change was analyzed by
      multivariate linear and nonlinear regression to yield an expected refractive
      change for each eye based on patient age and optical zone size. RESULTS:
      Residuals, defined as the difference between the achieved and expected refractive
      change, were normally distributed. The SD of the residuals was 0.68 diopter and
      was independent of the expected correction. The prediction of second-eye
      refractive change was not significantly improved by incorporating the residual
      from the first eye into the regression prediction. CONCLUSIONS: The SD of the
      difference between the achieved and expected refractive change is an appropriate
      measure of the variability in refractive outcome following a refractive surgical
      procedure. Surgeons who perform bilateral simultaneous radial keratotomy do not
      sacrifice refractive accuracy in the second eye.

PMID- 9186120
TI  - A polymerase chain reaction-based assay for diagnosing varicella-zoster virus
      retinitis in patients with acquired immunodeficiency syndrome.
AB  - PURPOSE: To develop a rapid, sensitive, and specific laboratory assay based on
      the polymerase chain reaction for the diagnosis of varicella-zoster virus
      retinitis in patients with acquired immunodeficiency syndrome (AIDS). METHODS: We
      developed and tested a polymerase chain reaction-based assay for the detection of
      varicella-zoster virus DNA in vitreous samples. We attempted to detect varicella
      zoster virus DNA in 14 vitreous samples from patients with AIDS and a clinical
      diagnosis of progressive outer retinal necrosis syndrome. For controls, we also
      attempted to detect varicella-zoster virus DNA in vitreous samples from 75
      immunocompetent patients with vitreoretinal disease and 88 patients with AIDS and
      vitreoretinal inflammatory disease not related to progressive outer retinal
      necrosis syndrome. RESULTS: Varicella-zoster virus DNA was detected in 11 of 14
      vitreous samples from AIDS patients with progressive outer retinal necrosis
      syndrome. All three samples that scored negative for varicella-zoster virus DNA
      came from eyes that had been treated aggressively with antiviral drugs and had
      clinically inactive disease at the time of vitreous biopsy. Varicella-zoster
      virus DNA was detected in only two of 75 control vitreous samples from
      immunocompetent patients with vitreoretinal disease and two of 88 control
      vitreous samples from patients with AIDS and vitreoretinal inflammatory disease
      not related to progressive outer retinal necrosis syndrome. CONCLUSION: We have
      developed a rapid, sensitive, and specific polymerase chain reaction-based
      diagnostic assay for varicella-zoster virus DNA that will assist in the diagnosis
      of varicella-zoster virus retinitis in patients with AIDS.

PMID- 9186122
TI  - Optic disk appearance in pseudoexfoliation syndrome.
AB  - PURPOSE: To evaluate the optic disk appearance in eyes with pseudoexfoliation
      syndrome. METHODS: Clinical data and color stereo optic disk photographs of 99
      patients with pseudoexfoliative glaucoma and 42 nonglaucomatous subjects with
      pseudoexfoliation syndrome were compared with those of 658 patients with primary
      open-angle glaucoma and of 364 normal subjects. RESULTS: Mean optic disk area was
      significantly (P = .009) smaller in the pseudoexfoliative glaucomatous eyes (mean
      +/-SD, 2.52 +/- 0.49 mm2) than in the primary open-angle glaucoma eyes (2.71 +/-
      0.63 mm2). Correspondingly, mean optic disk area was significantly (P = .04)
      smaller in the pseudoexfoliative nonglaucomatous eyes (2.48 +/- 0.52 mm2)
      compared with the normal eyes without pseudoexfoliation (2.67 +/- 0.67 mm2).
      Comparing the pseudoexfoliative subgroups with the nonpseudoexfoliative subgroups
      separately in the glaucomatous and the nonglaucomatous groups, no significant
      differences were found for neuroretinal rim area, size of alpha and beta zones of
      the parapapillary atrophy, and diameters of the retinal arterioles and venules at
      the disk border. In the glaucomatous group, the maximal intraocular pressure
      measurements were significantly (P < .001) higher in the pseudoexfoliative
      subgroup than in the subgroup with primary open-angle glaucoma. CONCLUSIONS:
      Except for a slightly smaller optic disk, eyes with pseudoexfoliative glaucoma
      and eyes with primary open-angle glaucoma do not vary significantly in their
      optic disk appearance despite significantly higher intraocular pressure peaks in
      pseudoexfoliative glaucoma. In eyes with pseudoexfoliation syndrome, a small
      optic disk does not predispose to glaucoma. In contrast with the anterior segment
      of the eye, the optic disk does not show pathognomonic features for
      pseudoexfoliation.

PMID- 9186123
TI  - Macular complications associated with posterior staphyloma.
AB  - PURPOSE: To report macular abnormalities associated with posterior staphyloma in
      eyes with myopia. METHODS: In a retrospective study, we surveyed 116 eyes of 58
      patients with myopic refractions. Myopic fundus abnormalities are related to
      clinically quantified posterior staphyloma formation. RESULTS: A posterior
      staphyloma was present in 88 (75.9%) of 116 eyes with myopic refractions of -3
      diopters or more. Best-corrected visual acuity was decreased among eyes in all
      staphyloma grades. Eyes with the shallowest staphyloma depth (grade 1) displayed
      the largest drop in visual acuity as well as the greatest frequency of choroidal
      neovascular membranes and hemorrhages. A linear relationship was observed between
      staphyloma grade and conus formation (P = .001), retinal pigment epithelial
      defects (P = .0001), lacquer cracks (P = .0001), and chorioretinal atrophy (P =
      .001). All these variables were increased in staphylomatous eyes. A significant
      difference in means by staphyloma grade was observed for myopic refractive error
      (P = .001), axial length (P = .001), and best-corrected visual acuity (logMAR, P
      = .0001). CONCLUSIONS: There was an unexpected high frequency of choroidal
      neovascular membranes, hemorrhage, and poor best-corrected visual acuity in the
      lower staphyloma categories. This suggests that the development of a choroidal
      neovascular membrane requires relative preservation of the choriocapillaris as
      present in eyes with less advanced stages of posterior staphyloma formation.

PMID- 9186124
TI  - Argon laser retinal lesions evaluated in vivo by optical coherence tomography.
AB  - PURPOSE: To assess the in vivo evolution of argon laser retinal lesions by
      correlating the cross-sectional structure from sequential optical coherence
      tomography with histopathologic sectioning. METHODS: Argon laser lesions were
      created in the retinas of Macaca mulatta and evaluated by cross-section optical
      coherence tomography, which was compared at selected time points with
      corresponding histopathology. RESULTS: Argon laser lesions induced an optical
      coherence tomography pattern of early outer retinal relative high reflectivity
      with subsequent surrounding relative low reflectivity that correlated well with
      histopathologic findings. The in vivo optical coherence tomography images of
      macular laser lesions clearly demonstrated differences in pathologic response by
      retinal layer over time. CONCLUSION: The novel sequential imaging of rapidly
      evolving macular lesions with optical coherence tomography provides new insight
      into the patterns of acute tissue response by cross-sectional layer. This
      sequential imaging technique will aid in our understanding of the rapid evolution
      of retinal pathology and response to treatment in the research and clinical
      setting.

PMID- 9186125
TI  - Familial aggregation of age-related maculopathy.
AB  - PURPOSE: To determine whether age-related maculopathy aggregates in families by
      evaluating whether its prevalence is higher among relatives of case subjects with
      age-related maculopathy compared with relatives of control subjects without age
      related maculopathy. METHODS: Individuals with (n = 119) and without (n = 72) age
      related maculopathy were identified. First-degree relatives of case and control
      probands (parents, siblings, or offspring) 40 years of age or older were asked
      whether they had ever been diagnosed with macular degeneration. Medical records
      of 177 case and 146 control relatives confirmed the presence or absence of age
      related maculopathy. RESULTS: The prevalence of medical-record confirmed age
      related maculopathy was significantly higher among first-degree relatives of case
      probands (23.7%) compared with first-degree relatives of control probands (11.6%)
      with an age- and sex-adjusted odds ratio (OR), 2.4; 95% confidence interval (CI),
      1.2 to 4.7; P = .013. Relatives of 78 case probands with exudative disease had a
      significantly higher prevalence of maculopathy (26.9%) compared with relatives of
      the 72 unaffected control probands (11.6%) (adjusted OR, 3.1; 95% CI, 1.5 to 6.7;
      P = .003), whereas the prevalence of age-related maculopathy among relatives of
      41 probands with dry maculopathy (19.2%) was slightly but not significantly
      higher (adjusted OR, 1.5; 95% CI, 0.6 to 3.7; P = .36). CONCLUSIONS: The
      prevalence of age-related maculopathy among first-degree relatives of subjects
      with age-related maculopathy, particularly with exudative disease, is greater
      than among first-degree relatives of subjects without this disease. Results
      suggest that macular degeneration has a familial component and that genetic or
      shared environmental factors, or both, contribute to its development.

PMID- 9186126
TI  - Focal macular electroretinogram before and after drainage of macular subretinal
      hemorrhage.
AB  - PURPOSE: To record and evaluate change in preoperative and postoperative macular
      electroretinograms in patients undergoing surgical drainage of macular subretinal
      hemorrhage. METHODS: Five eyes of five patients with good visual acuity before
      onset of hemorrhage underwent vitrectomy between 3 and 14 days after developing
      hemorrhage, with drainage of submacular hemorrhage, using recombinant tissue
      plasminogen activator. The causes of subretinal hemorrhage were macroaneurysm in
      three eyes, age-related macular degeneration in one eye, and unknown in one eye.
      Visual acuity and macular electroretinograms were recorded preoperatively and
      postoperatively. RESULTS: In all eyes, preoperative electroretinographic response
      was remarkably reduced or not recordable. Postoperative visual acuity improved,
      and electroretinographic response recovered to about one half the amplitude of
      the fellow eye in every eye with a normal fellow eye. CONCLUSIONS: A nearly
      nonrecordable preoperative response on macular electroretinogram indicates severe
      dysfunction of the photoreceptors caused by the submacular hemorrhage. A
      postoperative recovered macular electroretinogram suggests that photoreceptor
      function is at least partially reversible with surgical intervention, including
      injection of recombinant tissue plasminogen activator into the subretinal space.

PMID- 9186127
TI  - Aspirin therapy in nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: To determine the benefit of aspirin in reducing the risk of nonarteritic
      anterior ischemic optic neuropathy in the fellow eye following its occurrence in
      the first eye. METHODS: A retrospective cohort study was conducted on 431
      patients, 153 of whom were and 278 of whom were not prescribed aspirin following
      the development of unilateral nonarteritic anterior ischemic optic neuropathy.
      RESULTS: The 2-year cumulative probability of nonarteritic anterior ischemic
      optic neuropathy in the fellow eye was 7% in the aspirin group and 15% in the no
      aspirin group, and 5-year cumulative probabilities were 17% and 20%,
      respectively. Compared with the no-aspirin group, the rate ratio for nonarteritic
      anterior ischemic optic neuropathy in the fellow eye in the aspirin-user group
      was 0.43 (95% confidence interval, 0.19 to 0.92) over the first 2 years and 0.68
      (95% confidence interval, 0.36 to 1.26) over the 5-year period. The overall
      calculated 5-year risk was 19%; however, if none of the patients with incomplete
      follow-up developed nonarteritic anterior ischemic optic neuropathy in the fellow
      eye, then the 5-year risk would be about 12%. CONCLUSIONS: The 5-year risk of
      nonarteritic anterior ischemic optic neuropathy occurring in the second eye is
      far lower than that reported by previous studies. Our results suggest a possible
      short-term but little or no long-term benefit to aspirin in reducing the risk of
      nonarteritic anterior ischemic optic neuropathy in the fellow eye. However, this
      finding must be viewed with caution because this study was not conducted
      prospectively with a controlled protocol.

PMID- 9186129
TI  - Secondary intraocular lens implantation after cataract surgery in children.
AB  - PURPOSE: To report results of secondary intraocular lens implantation after
      cataract surgery in children. METHODS: We reviewed clinical records for a 5-year
      period of patients who had cataract surgery in childhood and received a secondary
      intraocular lens implant. We studied indications for secondary intraocular lens
      placement; surgical procedures for intraocular lens implantation; preoperative
      and postoperative visual acuity, refractive error, and binocular status; and
      complications of the procedure. RESULTS: A secondary intraocular lens was placed
      in 28 eyes of 25 patients who had cataract surgery in childhood. In 20 eyes, the
      lenses were placed in the ciliary sulcus. The other eight eyes had insufficient
      capsular support for an intraocular lens; in two, the intraocular lens was placed
      in the anterior chamber and, in six, in the posterior chamber with suture
      fixation to the sclera. Twenty of 28 eyes (71%) had measurable improvement in
      visual acuity; only one eye had a decrease in visual acuity of 2 lines. Fifteen
      patients (54%) had a final refraction within 1.50 diopters of the fellow eye; 21
      (75%) were within 3.00 diopters. During follow-up, two eyes developed glaucoma.
      One had transient pressure elevation; one required two filtration procedures.
      Three patients required Nd:YAG capsulotomy. Six patients demonstrated Worth
      fusion at distance and near; three demonstrated 200 seconds of arc or better
      stereo visual acuity. CONCLUSION: Secondary placement of an intraocular lens in
      the posterior chamber appears to be a safe, effective alternative for correction
      of aphakia in the contact lens- or spectacles-intolerant child or young adult.

PMID- 9186128
TI  - Ocular morbidity in very low birth-weight infants with intraventricular
      hemorrhage.
AB  - PURPOSE: To document ocular outcomes and prevalence of ocular disease in very low
      birth-weight infants with intraventricular hemorrhage. METHODS: We
      retrospectively reviewed the records of all surviving very low birth-weight
      infants (1,500 g or less) admitted to the neonatal intensive care unit of our
      institution during 1992 and 1993. Of 252 survivors, 74 had complete
      ophthalmologic examinations at a mean adjusted age of 11 months. Of these 74
      infants, 38 had intraventricular hemorrhage. Chi-square and multivariate analysis
      were used for statistical testing, in controlling for race, sex, and birth
      weight, and for other disease processes associated with prematurity. RESULTS: Of
      38 infants with intraventricular hemorrhage, strabismus occurred in 14 (37%),
      esotropia in 12 (32%), and exotropia in two (5%). Of the 20 infants with grades
      III and IV intraventricular hemorrhage, 11 (55%) had esotropia; none had
      exotropia. Infants with grades III and IV intraventricular hemorrhage were at
      significantly greater risk for the development of esotropia than were infants
      with less severe or no hemorrhage (odds ratio, 5.0; P = .04). Mean adjusted age
      at diagnosis of strabismus was 8.5 months. Infants with periventricular
      leukomalacia (odds ratio, 6.3; P = .036) and neonatal seizures (odds ratio, 7.3;
      P = .019) were at significantly greater risk of developing optic atrophy.
      CONCLUSIONS: Very low birth-weight infants with more severe neurologic morbidity
      are at significant risk for development of esotropia and optic atrophy.
      Ophthalmologic screening of all very low birth-weight survivors may allow earlier
      diagnosis and intervention for these at-risk infants.

PMID- 9186130
TI  - Strabismus and mitochondrial defects in chronic progressive external
      ophthalmoplegia.
AB  - PURPOSE: To describe the results of strabismus surgery on three patients with
      chronic progressive external ophthalmoplegia, a group of rare disorders
      characterized by ptosis and slowly progressive ophthalmoparesis that has been
      shown to result from defects in mitochondrial DNA. METHODS: Strabismus surgery
      using the adjustable suture technique was performed in three patients with
      strabismus and chronic progressive external ophthalmoplegia confirmed by
      clinical, biochemical, histopathologic, and genetic criteria. All three patients
      had mitochondrial DNA deletions. Two patients were exotropic; one patient was
      esotropic. RESULTS: Rectus muscle recessions were initially unsuccessful in
      correcting strabismus in one patient, although a subsequent procedure employing
      rectus muscle resections was successful in alleviating a significant head turn
      and improved ocular alignment. In the two other patients, a single procedure
      consisting of rectus muscle recessions combined with large rectus muscle
      resections successfully achieved good postoperative alignment. The amount of
      surgery performed in these three patients exceeded that predicted in standard
      strabismus tables. CONCLUSIONS: The myopathic process that results in chronic
      progressive external ophthalmoplegia renders rectus muscle recessions less
      effective compared with resections for correcting the associated strabismus seen
      in these patients. Rectus muscle resections therefore should be an integral
      procedure in the surgical management of the strabismus associated with chronic
      progressive external ophthalmoplegia.

PMID- 9186131
TI  - The potential impact of the varicella vaccine and new antivirals on ocular
      disease related to varicella-zoster virus.

PMID- 9186132
TI  - Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction.
AB  - PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a
      worsening corneal ulcer. METHODS: A 6-year-old boy underwent an emergent
      penetrating keratoplasty for a corneal ulcer that continued to worsen despite
      intensive antibiotic therapy. RESULTS: Examination of the corneal specimen by
      polymerase chain reaction was positive for varicella-zoster virus but negative
      for herpes simplex. Based on polymerase chain reaction studies, we diagnosed
      primary varicella-zoster keratitis with corneal perforation. Electron microscopy
      showed herpetic virus particles in the cornea. CONCLUSIONS: Polymerase chain
      reaction analysis of corneal buttons at the time of penetrating keratoplasty may
      benefit patients with undiagnosed recalcitrant corneal ulcers.

PMID- 9186133
TI  - Disciform keratitis: a case of herpes zoster sine herpete.
AB  - PURPOSE: To describe a case of disciform keratitis in a patient with acquired
      immunodeficiency syndrome (AIDS) in which varicella-zoster virus was the
      causative agent. METHOD: Case report, Polymerase chain reaction-based assays for
      varicella-zoster virus, cytomegalovirus, and herpes simplex virus were used to
      analyze an aqueous aspirate. RESULTS: We examined a 41-year-old man with AIDS but
      without a history of varicella-zoster virus dermatitis who had disciform corneal
      edema in his left eye. Varicella-zoster virus was detected by a polymerase chain
      reaction-based assay in the aqueous of the left eye; however, neither
      cytomegalovirus nor herpes simplex virus DNA were detected by polymerase chain
      reaction-based assays. The corneal edema slowly resolved while the patient was
      treated with famciclovir. CONCLUSION: Varicella-zoster virus may cause disciform
      keratitis without a preceding skin eruption.

PMID- 9186134
TI  - Famciclovir for the treatment of acute retinal necrosis (ARN) syndrome.
AB  - PURPOSE: To document a case of acute retinal necrosis syndrome in an
      immunocompetent patient who was successfully treated with famciclovir after
      unsuccessful treatment with acyclovir. METHODS: After diagnosing acute retinal
      necrosis syndrome in the patient's left eye, we treated him with 13 mg/kg/24
      hours of intravenous acyclovir in three daily doses for 14 days, followed by 800
      mg of acyclovir five times per day orally. New areas of retinitis developed
      within the posterior pole despite treatment with the maximum dosage of acyclovir;
      thus, we used a new antiviral agent, famciclovir. RESULTS: When we administered
      500 mg of famciclovir orally every 8 hours for 3 months, the retinitis regressed
      within 1 month, leaving atrophic granular pigmented scars. CONCLUSION:
      Famciclovir can effectively treat acute retinal necrosis syndrome in
      immunocompetent patients.

PMID- 9186135
TI  - Cytomegalovirus-associated acute retinal necrosis syndrome.
AB  - PURPOSE: To describe a case of acute retinal necrosis syndrome in which a
      polymerase chain reaction-based assay provided evidence for cytomegalovirus as
      the causative agent of the syndrome. METHODS: Polymerase chain reaction-based
      assays were used to analyze a vitreous aspirate from a 70-year-old man with acute
      retinal necrosis syndrome. The specimen was tested for cytomegalovirus, varicella
      zoster virus, and herpes simplex virus type 1 and type 2. RESULTS: The polymerase
      chain reaction assay for cytomegalovirus was positive, and polymerase chain
      reaction assays for varicella-zoster virus and herpes simplex virus type 1 and
      type 2 were negative. CONCLUSION: Cytomegalovirus may be a causative agent of
      acute retinal necrosis syndrome.

PMID- 9186136
TI  - Uveitis as the only clinical manifestation of poststreptococcal syndrome.
AB  - PURPOSE: To report a case of streptococcal infection of the upper respiratory
      tract in which bilateral anterior uveitis was the only complication. METHOD:
      Serologic documentation of post-streptococcal immune disease. The duration of
      inflammation was consistent with other forms of poststreptococcal immune disease.
      RESULTS: Bilateral anterior uveitis was treated with corticosteroids alone and
      resolved without ophthalmic complications. CONCLUSION: Bilateral anterior uveitis
      may be the only clinical manifestation of poststreptococcal syndrome.

PMID- 9186137
TI  - Endogenous endophthalmitis caused by Streptococcus mitis.
AB  - PURPOSE: To report endogenous endophthalmitis caused by Streptococcus mitis.
      METHODS: A 3-year-old girl was hospitalized for possible retinoblastoma after she
      suddenly developed a red and sensitive left eye. After administration of
      anesthesia, we examined the patient and obtained samples of aqueous, vitreous,
      and blood for culture. RESULTS: Blood and vitreous cultures grew S mitis.
      Intravenous and intravitreal injections of antibiotics were used to treat the
      infection. CONCLUSIONS: Streptococcus mitis should be considered a cause of
      endogenous endophthalmitis.

PMID- 9186138
TI  - A new approach to the surgical management of idiopathic uveal effusion syndrome.
AB  - PURPOSE: To describe a new method for managing retinal detachment associated with
      idiopathic uveal effusion syndrome. METHODS: A 73-year-old man with idiopathic
      uveal effusion syndrome and total retinal detachment in the right eye underwent
      quadrantic partial-thickness sclerectomies in conjunction with pars plana
      vitrectomy, internal drainage of subretinal fluid, and fluid-gas exchange.
      RESULTS: In the right eye, the patient's retina remained attached for 1 year
      after the procedure, and visual acuity improved to 20/70 on final follow-up.
      CONCLUSION: Internal drainage of subretinal fluid performed in conjunction with
      quadrantic partial-thickness sclerectomies may be a preferred method of treating
      secondary retinal detachment in idiopathic uveal effusion syndrome. This
      procedure hastens reattachment of the neurosensory retina and may thereby improve
      the visual outcome.

PMID- 9186139
TI  - Vitreous cells as an indicator of retinal tears in asymptomatic or not recently
      symptomatic eyes.
AB  - PURPOSE: To define the relationship between vitreous cells and retinal tears in
      eyes without recent flashes or floaters. METHODS: Five hundred eighty-five
      consecutive patients who complained of light flashes, floaters, or both in one
      eye had their asymptomatic or not recently symptomatic fellow eye examined
      prospectively for vitreous cells and retinal tears. RESULTS: Of these fellow eyes
      with 2+ or more vitreous cells (10 or more cells per 1-mm slit-lamp field), 31.6%
      (6/19) had one or more tears vs 1.6% (9/566) of those with 1+ or fewer cells
      (less than nine cells per 1-mm slit-lamp field) (P = .0001). CONCLUSIONS: A
      substantial number of vitreous cells, even in an eye with no recent symptoms, is
      correlated with the presence of a retinal tear. Additionally, a retinal tear may
      exist in an eye with 1+ or fewer cells.

PMID- 9186140
TI  - Conjunctival biopsy in infantile neuroaxonal dystrophy.
AB  - PURPOSE: To describe a case of infantile neuroaxonal dystrophy with optic nerve
      atrophy and to discuss the diagnostic role of conjunctival biopsy. METHODS: We
      performed a complete ophthalmologic examination and a diagnostic conjunctival
      biopsy on a girl with a neurodegenerative disease. RESULTS: On the basis of
      "spheroid" inclusions in the unmyelinated axons, we diagnosed infantile
      neuoroaxonal dystrophy. CONCLUSIONS: Optic atrophy is an important finding in
      infantile neuroaxonal dystrophy, and conjunctival biopsy is a reliable and very
      convenient diagnostic test.

PMID- 9186141
TI  - Conjunctival metastasis from a cutaneous melanoma as the initial sign of
      dissemination.
AB  - PURPOSE: We report a case in which a conjunctival metastasis from a cutaneous
      melanoma was the first sign of metastatic disease. METHOD: An excisional biopsy
      of an amelanotic pedunculated conjunctival lesion in a 52-year-old man showed
      epithelioid melanoma. RESULTS: Systemic examination showed widespread
      disseminated disease from a cutaneous melanoma that had been removed 3 1/2 years
      earlier. At that time, no signs of metastatic disease were detected. Despite
      chemotherapy, the patient died 6 weeks later. CONCLUSION: Conjunctival metastasis
      from a cutaneous melanoma is a rare and ominous sign of widely disseminated
      disease.

PMID- 9186142
TI  - Papillary adenocarcinoma of the ciliary body simulating retinoblastoma.
AB  - PURPOSE: To report a 2 1/2-year-old boy who had papillary adenocarcinoma of the
      ciliary body that simulated retinoblastoma. METHOD: Initially treated for
      congenital glaucoma, the patient was referred with a white mass involving the
      iris, chamber angle, and ciliary body. RESULTS: Enucleation of the right eye,
      which was initially diagnosed as retinoblastoma, showed a papillary
      adenocarcinoma of the ciliary body epithelium involving the posterior chamber,
      iris, anterior chamber, and trabeculum. CONCLUSION: Adenocarcinoma of the ciliary
      body must be included in the differential diagnosis of tumors originating from
      the ciliary body in young children.

PMID- 9186143
TI  - Cavitation in ciliary body melanoma.
AB  - PURPOSE: To report a case of a cystic ciliary body melanoma that appeared
      clinically as a solid mass. METHODS: A 59-year-old woman underwent an
      iridocyclectomy for removal of a ciliary body melanoma in the right eye. The
      tumor was analyzed histopathologically for acid mucopolysaccharide production.
      RESULTS: Histopathology identified a ciliary body melanoma with cystic cavities.
      Contents of the cystic spaces did not stain with alcian blue. Histologic findings
      suggested exudation, cavitary necrosis, or both rather than acid
      mucopolysaccharide production as pathogenic factors for cyst formation.
      CONCLUSION: Cystic cavities can develop in a solid, malignant tumor and therefore
      should not be considered signs of a benign lesion.

PMID- 9186144
TI  - Metastatic liposarcoma to the orbit.
AB  - PURPOSE: To report a woman with blurred vision and proptosis who harbored an
      orbital liposarcoma that had metastasized from her abdomen. METHODS: The patient
      underwent an orbital biopsy, followed by postoperative intravenous
      corticosteroids and radiation. RESULTS: Pathology showed a dedifferentiated
      liposarcoma. The patient's visual acuity improved from 20/200 to 20/50 after
      treatment. CONCLUSIONS: Physicians should suspect the presence of this rare
      orbital tumor in a person with a history of liposarcoma who has proptosis.
      Liposarcomas usually exhibit a higher grade of malignancy with recurrence, as
      shown in this patient.

PMID- 9186146
TI  - Nasal tuberculosis in the 20th century.
AB  - During the last decade, tuberculosis has reemerged as a major health problem in
      the United States. Much of the blame for this resurgence has been attributed to
      human immunodeficiency virus infection, although homelessness and deterioration
      of the social infrastructure have also been implicated. Extrapulmonary
      tuberculosis is uncommon, and nasal tuberculosis is rare. The latter usually
      manifests as nasal obstruction or discharge. Only 35 cases of nasal tuberculosis
      were identified in a search of the English-language medical literature from the
      last 95 years. They are reviewed here. In addition, we describe a new
      manifestation of nasal tuberculosis, exemplifying the variety of ways in which
      this may occur.

PMID- 9186145
TI  - Tuberculous meningitis at a large inner-city medical center.
AB  - Tuberculosis in the United States has become primarily an inner-city disease. We
      examined the epidemiology of culture-confirmed tuberculous meningitis among
      patients cared for at an urban public hospital in Atlanta. During an 11.5-year
      period (January 1984-June 1995) cerebrospinal fluid cultures for Mycobacterium
      tuberculosis were positive in 34 patients, accounting for 1.5% of all culture
      confirmed tuberculosis cases. All patients were born in the United States, 31
      (91%) were black, 16 (47%) of 34 were human immunodeficiency virus (HIV)
      seropositive, 9 (26.5%) were HIV seronegative, and 9 (26.5%) had an unknown HIV
      serostatus. No significant differences were seen in clinical presentation,
      cerebrospinal fluid, or other laboratory data between HIV seropositive and HIV
      seronegative/ unknown groups, except for a lower serum white blood cell count
      among HIV seropositive patients. Mortality was striking; 14 (41.2%) died because
      of tuberculous meningitis despite appropriate therapy initiated a mean of 3 days
      after admission. Six survivors had permanent neurologic sequelae. Univariate
      analysis of outcome was not statistically associated with any measured
      demographic, laboratory value, stage at presentation, treatment regimen, or HIV
      serostatus. Multivariate analysis of outcome using 13 independent variables also
      demonstrated no significant association between these variables and outcome,
      although a trend was seen for increased mortality for white people (P = 0.09) and
      increasing age (P = 0.09). Tuberculous meningitis among inner-city residents
      remains a devastating disease associated with high morbidity and mortality that
      has changed little during the past 4 decades. HIV infection does not change
      markedly the clinical presentation or the response to therapy.

PMID- 9186147
TI  - Epidemiology of pediatric tuberculosis in Chicago, 1974 to 1994: a continuing
      public health problem.
AB  - Despite downward trends in the overall rate of tuberculosis in the United States
      for 1993 to 1994, the rate among children (0 to 14 years) has increased. To
      evaluate the trend in pediatric tuberculosis in Chicago and better direct public
      health efforts to control tuberculosis, we analyzed summary data for 1974 to 1981
      and detailed data for 1982 to 1994 from surveillance case reports. These data
      were compared to the 1980 and 1990 census data for the 77 community areas in
      Chicago. Of the 18,700 cases of tuberculosis reported in Chicago for the study
      period, 702 (3.8%) occurred in children. Children accounted for a significantly
      increasing proportion of reported cases, 204/7093 (2.9%) in 1974 to 1981 versus
      498/11,607 (4.3%) in 1982 to 1994, a trend which began in 1982. The number of
      cases among immigrants remained low throughout the study. Sites of infection were
      as follows: 73% pulmonary parenchymal disease, 9% hilar adenopathy, 9%
      extrathoracic lymph adenopathy, 3% meningitis, 3% miliary, and 3% other. From
      1982 to 1994, 13 communities had a total of 224 cases (45%); average rates were >
      10/100,000 in the population under 15 years old, and 7 of these communities had
      127 cases (25%); average rates were > 15/100,000. Of the 77 community areas, 16
      (21%) had no pediatric tuberculosis. Comparison of case rates with socioeconomic
      and health indicators showed the highest rates in communities with multiple
      indicators of poverty, including overcrowded housing units, low median income,
      and high infant mortality rates. Pediatric tuberculosis in Chicago remains a
      significant public health problem. Efforts to address this problem should provide
      resources to the community areas with the highest incidence rates.

PMID- 9186148
TI  - Geographic and seasonal variation in Mycobacterium avium bacteremia among North
      American patients with AIDS.
AB  - Analysis of geographic risk was performed for Mycobacterium avium complex (MAC)
      bacteremia among North American patients with AIDS. Monthly mycobacterial blood
      cultures were taken from patients who were placebo recipients in a prospective
      evaluation of MAC prophylaxis. Of 571 patients, 102 (17.9%) acquired MAC
      bacteremia during an average follow-up of 256 days. The area with the highest
      risk for MAC was the South Central region (27.9%; P < 0.02), whereas the area
      with the lowest risk was Canada (11.3%; P = 0.12). When the southern states were
      combined and compared with the northern states and Canada, the incidence of MAC
      bacteremia was higher in the southern states (21.6% versus 14.0%, P < 0.03).
      Proportional hazards analysis was performed for the difference between the North
      and South and controlled for baseline CD4 cell count. In this analysis, time to
      MAC was significantly longer in the North (hazard ratio = 0.587, 95% confidence
      interval 0.390 to 0.883, P = 0.01). Although overall variation in seasonality was
      not marked, there was a significant decrease in cases in the North during the
      summer months (P < 0.01). We conclude that geographic location is a risk factor
      for MAC bacteremia in patients with advanced AIDS, with decreased risk in
      northern North America.

PMID- 9186149
TI  - Mycobacterium szulgai infection of the lung: case report and review of an unusual
      pathogen.
AB  - The nontuberculous mycobacteria are responsible for considerable morbidity in the
      immunocompromised and immunocompetent host, especially in the older patient with
      chronic fibrotic or cavitary disease of the lung. Mycobacterium szulgai is a slow
      growing mycobacterium infrequent in nature and man. Except from a snail and a
      tropical fish, it has been isolated only from humans and nearly always represents
      a true pathogen. Three-drug therapy using in vitro susceptibilities as a guide
      for 12 to 18 months increases the likelihood of success. We present a patient who
      developed M szulgai pulmonary infection 30 years after an episode of pulmonary
      tuberculosis. After successful therapy for his M szulgai infection, this patient
      developed chronic pulmonary histoplasmosis. We review the 25 years of clinical
      experience with this mycobacteria; particular emphasis is on the presentation and
      treatment of this very unusual infection.

PMID- 9186150
TI  - Similar serovar and drug susceptibility profiles among AIDS-related Mycobacterium
      avium isolates from diverse geographic locations.
AB  - Serotyping was performed on Mycobacterium avium isolates from 40 AIDS patients
      from 5 geographic sites: Boston (17 patients), New Hampshire (4 patients),
      Finland (12 patients), Trinidad (3 patients), and Kenya (4 patients). Serovars
      were similar from the five sites. Serovars 4 and 8 were the most common. In
      addition, minimal inhibitory concentrations to 8 antimicrobial agents were
      determined for 31 of these isolates and for 21 additional patient isolates from
      these sites. Minimal inhibitory concentration90 values for clarithromycin,
      azithromycin, clofazimine, amikacin, ethambutol, ciprofloxacin, sparfloxacin, and
      rifabutin were similar for isolates from the five geographic sites. Antimicrobial
      susceptibility patterns did not differ by serovar.

PMID- 9186151
TI  - The value of in vitro drug activity and pharmacokinetics in predicting the
      effectiveness of antimycobacterial therapy: a critical review.
AB  - Marked increases in case rates of drug-resistant tuberculosis and nontuberculous
      mycobacterial infections have brought renewed urgency to the development of new
      treatment regimens for mycobacterial infections. Preclinical data, such as in
      vitro measures of drug activity and pharmacokinetics, are used in the design of
      new treatment regimens. This review surveys the extensive published clinical
      experience concerning the treatment of drug-susceptible tuberculosis to evaluate
      the use of these preclinical measures in predicting clinical outcomes of
      antimycobacterial therapy. In vitro measures of drug activity predict the potency
      of a drug to prevent the emergence of resistance to other antimycobacterial drugs
      but do not predict the sterilizing activity of a drug or the activity of drug
      combinations. In vitro measures of drug activity do not allow reliable
      predictions of the level at which an organism should be considered resistant.
      Assays of drug penetration in tissues and activity against intracellular bacilli
      add modestly to the predictive value of in vitro measures of drug activity but
      still do not predict sterilizing activity. In contrast, animal models of
      tuberculosis have predicted relative drug potency (including sterilizing
      activity), the efficacy of multidrug regimens, and the duration of therapy
      needed. Despite pharmacokinetic parameters that would suggest the need for
      multiple doses per day, all of the first-line antituberculous drugs are active
      when given as infrequently as twice weekly. It is difficult to predict the
      efficacy of therapy for an intracellular pathogen that has the capacity for
      dormancy. Better in vitro models are needed, particularly ones that predict
      sterilizing activity.

PMID- 9186152
TI  - In vitro cellular and cytokine responses to mycobacterial antigens: application
      to diagnosis of tuberculosis infection and assessment of response to
      mycobacterial vaccines.
AB  - Mycobacterial infection leads to the development of specific cell-mediated immune
      responses that have been measured clinically by assessing delayed-type
      hypersensitivity with Mantoux skin testing. Several characteristics of Mantoux
      skin testing for tuberculosis infection can make the procedure inaccurate,
      inconvenient, and sometimes misleading. It is also a poor predictor of immunity
      to tuberculosis in bacille Calmette-Guerin vaccinees, yet decisions to
      revaccinate often are based on skin test responses after initial immunization.
      Skin testing with other mycobacterial antigens has similar limitations. In vitro
      assessment of cellular immunity to mycobacteria offers multiple, potential
      advantages over skin testing and has become technically feasible in recent years.
      Measurement of the effector functions that comprise cell-mediated immunity (eg,
      cytokine secretion and cytotoxicity) rather than cutaneous delayed-type
      hypersensitivity responses is more likely to reflect meaningfully specific
      mycobacterial immunity and, therefore, provide a means for determining
      mycobacterial immunity after immunization. Eliminating the variability in
      placement and interpretation inherent in skin testing could provide a more stable
      foundation for comparative studies in populations and improve decision making for
      individuals. Finally, in vitro testing permits the use of discrete mycobacterial
      antigens instead of crude protein preparations, allowing greater specificity in
      the detection of infection as well as assessment of responses to defined
      candidate vaccine antigens. Several studies have compared skin testing with in
      vitro proliferation of lymphocytes stimulated by mycobacterial antigens for the
      detection of Mycobacterium tuberculosis infection. Preliminary veterinary and
      human studies suggest that in vitro assessment of gamma-interferon production in
      response to mycobacterial antigens can be used to detect prior infection with
      organisms of the M tuberculosis complex. Streamlined techniques for in vitro
      testing of cellular immunity may allow its practical adoption in the clinical
      setting and lead to its use as a replacement for Mantoux skin testing.

PMID- 9186153
TI  - Use of the bacille Calmette-Guerin vaccination for the prevention of
      tuberculosis: renewed interest in an old vaccine.
AB  - The reemergence of tuberculosis, including the impact of HIV infection and
      multidrug-resistant tuberculosis, have renewed interest in the bacille Calmette
      Guerin (BCG) vaccine. During the past 7 decades, numerous studies have shown
      variable efficacy of BCG vaccination, ranging from 0% to 80%. The BCG vaccine is
      more likely to prevent disseminated forms of tuberculosis in children than
      pulmonary tuberculosis in adolescents or adults. Bacille Calmette-Guerin
      vaccination is recommended in asymptomatic children with or at risk for HIV
      infection, but it rarely may cause disseminated BCG infection and should not be
      used in persons with symptomatic HIV infection or AIDS. In healthcare workers
      with exposure to Mycobacterium tuberculosis, including multidrug-resistant
      tuberculosis, BCG vaccination generally is not recommended. Revaccination with
      BCG does not confer more benefit than initial vaccination, and repeat
      vaccinations should be discontinued. With recent advances in technology and a
      better understanding of the immunopathogenesis of tuberculosis, efforts to
      develop a more potent and specific vaccine need to be pursued. If a more
      effective vaccine against tuberculosis is developed, vaccination can be expected
      to have an additional impact on global tuberculosis control in conjunction with
      current strategies of case detection, treatment of disease, and preventive
      therapy.

PMID- 9186154
TI  - Immunization of HIV-infected adults with a three-dose series of inactivated
      Mycobacterium vaccae.
AB  - Heat-killed Mycobacterium vaccae vaccine was administered in a 3-dose schedule to
      12 HIV-infected adults with CD4 cell counts > or = 300/mm3. Local and systemic
      side effects were monitored. Delayed-type hypersensitivity to purified protein
      derivative and Mycobacterium avium sensitin was measured at baseline and after
      the final dose. Antibody to aralipoarabinomannin, man-lipoarabinomannin, and a
      short-term culture filtrate of Mycobacterium tuberculosis were also measured.
      Lymphocyte proliferation responses to M avium sensitin and M vaccae sonicate were
      determined. Vaccine site induration was maximal at 2 days (median, 6 mm) and no
      systemic side effects were noted. Purified protein derivative skin test
      conversions did not occur. Changes in CD4 counts and HIV viral load were not
      significant. Three (27%) of 11 subjects who completed the trial showed either M
      avium skin test (n = 1) or short-term culture filtrate antibody (n = 2)
      responses. A three-dose schedule of M vaccae vaccine is safe and well tolerated
      in adults with early HIV infection and produces detectable immunologic responses
      in a subset of these subjects.

PMID- 9186155
TI  - Stroke prevention in atrial fibrillation.

PMID- 9186156
TI  - Medical associations: guilds or leaders?

PMID- 9186157
TI  - Should trusts be allowed to fail?

PMID- 9186158
TI  - British doctors are not disappearing.

PMID- 9186159
TI  - Tackling deficient doctors.

PMID- 9186160
TI  - Tobacco industry memo reveals passive smoking strategy.

PMID- 9186164
TI  - American Medical Association backs amended abortion bill.

PMID- 9186162
TI  - Medical Research Council is to abolish project grants.

PMID- 9186165
TI  - Panel defends India's traditional doctors.

PMID- 9186166
TI  - GMC issues guidelines on circumcision.

PMID- 9186167
TI  - Health authority stops buying homoeopathy.

PMID- 9186168
TI  - Intentions of newly qualified doctors to practise in the United Kingdom.

PMID- 9186169
TI  - Role of medical factors in 1000 fatal aviation accidents: case note study.

PMID- 9186170
TI  - Interaction of thyroxine sodium with antimalarial drugs.

PMID- 9186171
TI  - Acute renal failure due to rhabdomyolysis in presence of concurrent ciprofibrate
      and ibuprofen treatment.

PMID- 9186172
TI  - Postal survey of patients' satisfaction with a general practice out of hours
      cooperative.
AB  - OBJECTIVE: To assess patients' satisfaction with out of hours care by a general
      practice cooperative compared with that by a deputising service. DESIGN: Postal
      questionnaire survey. SETTING: A general practice cooperative in London and a
      deputising service operating in an overlapping area. SUBJECTS: Weighted samples
      of patients receiving telephone advice, a home visit, or attending a primary care
      centre after contacting either service in an eight week period. MAIN OUTCOME
      MEASURES: Patients' overall satisfaction and scores for specific aspects of
      satisfaction. Satisfaction with telephone advice or attendance at centre compared
      with home visit. Relation between satisfaction and patient's age, sex, ethnic
      group, car ownership, preference for consulting own doctor, and expectation of a
      visit. RESULTS: The overall response rate was 67% (1555/2312). There was little
      difference in overall satisfaction between patients contacting the cooperative or
      the deputising service, but patients contacting the latter were less satisfied
      with the explanation and advice received and the wait for a visit. There were
      significant differences between patients in different age and ethnic groups, with
      white patients and those aged over 60 years being more satisfied. Lower scores
      for overall satisfaction were reported by patients who received telephone advice,
      those who would have preferred to see their own doctor or who originally wanted a
      home visit, and those who waited longer for their consultation. Overall levels of
      patients' satisfaction seemed to be lower than previously reported. CONCLUSIONS:
      There were larger differences in satisfaction between different groups of
      patients than between different models of organisation for out of hours care. A
      shift to a service based predominantly on telephone advice may lead to increased
      patient dissatisfaction.

PMID- 9186173
TI  - Evaluation of a general practice out of hours cooperative: a questionnaire survey
      of general practitioners.

PMID- 9186174
TI  - Using the technology of the World Wide Web to manage clinical information.

PMID- 9186175
TI  - Science, medicine, and the future. Substance use disorders.

PMID- 9186176
TI  - ABC of mental health. Common mental health problems in primary care.

PMID- 9186177
TI  - The performance of doctors. II: Maintaining good practice, protecting patients
      from poor performance.

PMID- 9186178
TI  - Health in China. The healthcare market.
AB  - It is now about 15 years since the introduction of the market into health care in
      China. This produced fundamental changes in the way that health care is financed
      and resulted in the disappearance of universal free basic health care.
      Responsibility for provision of health services has been devolved to the
      provincial and county governments, and healthcare providers have been given
      considerable financial independence. A fee for service system has been
      introduced, and several different payment mechanisms are now in operation. The
      new financing and pricing structures are responsible for greater inequity of
      access to services and more inefficient use of resources. These problems are
      widely acknowledged, and a range of solutions is being developed and tested.
      Since the introduction of the reforms the measurable health status of the
      population has not declined, probably as a result of overall improved
      socioeconomic conditions and a continued emphasis on prevention.

PMID- 9186179
TI  - Asian doctors are still being discriminated against.

PMID- 9186180
TI  - What happens when the private sector plans hospital services for the NHS.
      Authors' figures were wrong for Edinburgh...

PMID- 9186181
TI  - What happens when the private sector plans hospital services for the NHS ... and
      Bromley.

PMID- 9186182
TI  - What happens when the private sector plans hospital services for the NHS. An
      increase in hospital beds is not necessarily the best investment.

PMID- 9186183
TI  - What happens when the private sector plans hospital services for the NHS.
      Functions of district general hospitals have changed.

PMID- 9186184
TI  - What happens when the private sector plans hospital services for the NHS.
      Patients and staff need facilities required for modern medicine.

PMID- 9186185
TI  - Consensus statement on criteria for the persistent vegetative state is being
      developed.

PMID- 9186186
TI  - The future of Britain's high security hospitals. Primacy of patients must be re
      established as sole reason for hospitals' existence.

PMID- 9186187
TI  - The future of Britain's high security hospitals. Many staff working in secure
      psychiatric facilities want to be become members of Prison Officers' Association.

PMID- 9186188
TI  - Young people, alcohol, and designer drinks. Conventional drinks are a much
      greater threat to health than designer drinks.

PMID- 9186189
TI  - Legal abortions save women's lives.

PMID- 9186190
TI  - Abortion must not be advocated as preventive solution to unwanted pregnancy.

PMID- 9186191
TI  - Neonatal risk factors for cerebral palsy in very preterm babies. Time oriented
      analyses of risk are useful.

PMID- 9186192
TI  - United States has recommended screening for colon cancer. Why has barium enema
      been suggested?

PMID- 9186193
TI  - Oropharyngeal blood blisters are known as angina bullosa haemorrhagica.

PMID- 9186194
TI  - Vasospasm of the nipple was described in 1970.

PMID- 9186195
TI  - A classic in trauma education.

PMID- 9186196
TI  - Education in orthopaedic trauma.
AB  - Education of the orthopaedic surgeon in trauma care presents a unique challenge
      because of the need to acquire knowledge about the overall resuscitation of the
      patient as well as having a sound working knowledge of the treatment of injuries
      to other organ systems and how that treatment interplays with orthopaedic care in
      such complex disorders such as adult respiratory distress syndrome. The
      orthopaedic trauma educator requires special dedication and skill because much
      teaching occurs at night and on holidays and weekends in the context of emergency
      surgery where immediate decisions are required and procedures must be executed
      expeditiously and with minimal morbidity. An ideal educational program in trauma
      provides ready availability of the attending with close supervision of a team of
      residents lead by an experienced chief or fellow to whom appropriate graduated
      responsibility for decision making and execution of surgery is provided. A formal
      didactic course with a complete multidisciplinary curriculum is essential. The
      managed healthcare movement has the potential to disrupt the educational process
      and clinical research in orthopaedic trauma by reducing referrals to major trauma
      centers; by making high quality trauma treatment, particularly in the indigent
      population economically impractical; and by interfering with the patient care and
      educational and research process by early transfer of patients to other providers
      removed from the trauma center environment. Orthopaedic trauma educators must
      work with their institutions, national organizations, government, and the
      healthcare industry to develop methods to preserve and advance the education and
      research in trauma care which has served our population so well and is so
      important for the health and productivity of society in the future.

PMID- 9186197
TI  - Femoral neck fracture fixation. Clinical decision making.
AB  - Femoral neck fractures continue to pose significant decision making problems for
      the busy practitioner. Indirect factors over which the orthopaedic surgeon has
      little control include the patient's preinjury medical status, metabolic bone
      quality, and fracture classification. Direct factors that fall on the decision
      making ability of the surgeon include surgical timing, capsular hematoma, quality
      of reduction, and mechanics of fixation. Early, rigid anatomic reduction with 6.5
      mm compression screws in patients with few comorbidities will achieve the optimum
      outcomes using fixation techniques. Anterolateral open approaches afford capsular
      hematoma decompression and anatomic access for fixation in the young or
      irreducible fracture pattern.

PMID- 9186198
TI  - Extracorporeal life support for patients with significant orthopaedic trauma.
AB  - Extracorporeal life support is a therapeutic modality that can provide
      cardiorespiratory support for multiply injured patients. Fourteen patients with
      multiple trauma who sustained pelvic or long bone fractures were referred for
      treatment with extracorporeal life support at the University of Michigan Medical
      Center. All patients were considered morlbund secondary to their pulmonary
      injury. Six of the 14 patients had bilateral pulmonary contusions. The mean
      Injury Severity Score was 19. Twelve of the 14 patients had femoral or pelvic
      fractures or both. Eight patients had orthopaedic injuries initially treated with
      traction. The most common complication during extracorporeal life support
      management was bleeding, which occurred in eight of 14 patients. Eight of the 14
      patients survived. Seven of eight patients with less than 6 days of mechanical
      ventilation before initiation of extracorporeal life support survived. Only one
      of six patients with six or more days of mechanical ventilation before initiation
      of extracorporeal life support survived. Patients with significant orthopaedic
      trauma and severe pulmonary compromise have an extremely high mortality risk.
      Appropriate aggressive fracture management remains the most important
      intervention to decrease the risk of pulmonary compromise. Early initiation of
      extracorporeal life support can be an additional lifesaving intervention in
      select patients with orthopaedic trauma who have respiratory failure refractory
      to conventional mechanical ventilation.

PMID- 9186200
TI  - Treatment of tibial plateau fractures by limited internal fixation.
AB  - Seventy-five adults who sustained 76 tibial plateau fractures were treated
      according to a prospective protocol using instability in extension as the
      principal indication for operative fixation. Patients showing instability
      underwent closed manipulative reduction under fluoroscopic guidance. If
      significant joint depression persisted after reduction, elevation of the fracture
      was performed either from below using bone punches through a cortical window or
      via limited arthrotomy. Iliac crest bone graft was used to buttress depressed
      fractures. Fixation was then secured using 7-mm cannulated screws with washers or
      buttress plates and screws. Postoperatively, 58 of 76 knees were managed in a
      hinged knee brace, allowing the patient early range of motion and protected
      weightbearing for 8 weeks. Patients who were found to have a stable knee were
      treated with Bledsoe braces according to the postoperative protocol. In the 75
      patients, 18 of the 76 knees were unsuitable for percutaneous screw fixation
      because of fracture complexity requiring plates, severe open injuries, or
      inadequate reductions with limited fixation had been done. A minimum followup of
      12 months was obtained in 55 patients (range, 12-59 months). All fractures had
      healed at the time of followup. Eighty-seven percent of the patients at followup
      had a successful outcome using Rasmussen's criteria. Fourteen of these patients
      had arthroscopic assisted reduction or evaluation. All seven patients who had
      poor outcomes had AO Type C3 fracture patterns. Severely depressed or comminuted
      fractures or fractures with significant metaphyseal diaphyseal extension may not
      be suitable for this technique and require the addition of an external fixation
      device or buttress plate to maintain the reduction and allow for early range of
      motion.

PMID- 9186199
TI  - Reamed femoral nailing in patients with multiple injuries. Adverse effects of
      tourniquet use.
AB  - Limb reperfusion after tourniquet ischemia causes pulmonary microvascular injury.
      Similarly, microembolization, like that associated with reamed femoral nailing,
      can induce pulmonary microvascular injury. Both processes result in increased
      pulmonary capillary membrane permeability and edema. However, the association
      between femoral nailing followed by tourniquet ischemia and clinical lung injury
      has not been described. The authors reviewed 72 patients with femoral shaft
      fractures and tibial or ankle fractures requiring internal fixation between 1987
      and 1993. All femoral shaft fractures were treated with reamed intramedullary
      nails. Patients were divided into groups, based on whether the tibial or ankle
      injury was managed surgically with (Group T, 34 patients) or without (Group NT,
      38 patients) a tourniquet. Group T was subdivided based on tourniquet time: T1,
      less than or equal to 90 minutes; T2, greater than 90 minutes. Groups were
      matched for injury severity. Group NT had fewer ventilator dependent days and
      intensive care days than Group T (NT: ventilator dependent days, 2.5 +/- 5.2;
      intensive care days, 3.9 +/- 6.5; T: 5.1 +/- 6.4; intensive care days, 6.7 +/-
      6.6). Ventilator dependent days and intensive care days increased with increasing
      tourniquet time (T1: ventilator dependent days, 3.2 +/- 3.6; intensive care days,
      5.4 +/- 4.6; T2: ventilator dependent days, 7.5 +/- 8.5; intensive care days, 8.5
      +/- 8.5), suggesting that in patients with multitrauma, combining reamed femoral
      nailing with fracture fixation under tourniquet control increases pulmonary
      morbidity. Further investigation to measure pulmonary injury associated with
      ischemia reperfusion and intramedullary nailing in patients with multitrauma is
      warranted.

PMID- 9186202
TI  - Decision making errors in the use of interlocking tibial nails.
AB  - Seventy-one fractures of the tibial shaft were treated with interlocking
      intramedullary nails. None of the fractures were treated with static locking of
      the intramedullary nails. These 71 fractures were studied to determine whether
      certain fracture patterns are prone to loss of alignment when static interlocking
      is not used. Loss of alignment was defined as shortening of 1 cm or more and/or
      change in angulation of at least 5 degrees. Loss of alignment occurred in eight
      of the 71 (11%) fractures. Shortening and/or angulation occurred in seven of 22
      spiral and short oblique fractures, and in none of 27 transverse fracture
      patterns. It was concluded that the dynamically locked and nonlocked modes of
      intramedullary nailing should not be used in the stabilization of spiral and
      oblique fractures of the tibial shaft.

PMID- 9186201
TI  - Nonreamed locking intramedullary nailing for open fractures of the tibia.
AB  - The use of nonreamed interlocking tibial nails in the management of open
      fractures of the tibial shaft has gained wide acceptance. This technique has been
      reported to have reproducible good results with a low incidence of complications
      in Type I, Type II, and Type IIIA open tibial shaft fractures. The use of
      nonreamed nails in Type IIIB fractures continues to be a source of controversy.
      The treatment of 72 open fractures of the tibial shaft with nonreamed
      interlocking intramedullary nailing is detailed. There were 27 Type I, 22 Type
      II, 11 Type IIIA, and 12 Type IIIB open tibial shaft fractures. There were three
      (4.2%) deep infections; one Type II, one Type IIIA, and one Type IIIB. Forty-nine
      fractures (68%) united by 6 months, all fractures had united by 12 months. The
      use of nonreamed locking intramedullary nailing in Types I, II, IIIA, and IIIB
      open fractures of the tibial shaft is supported.

PMID- 9186203
TI  - Efficacy of cultures in the management of open fractures.
AB  - Two hundred forty-five open fractures were reviewed retrospectively to determine
      the prognostic value of wound bacterial cultures concerning deep infections
      requiring surgical management. Only 8% of organisms grown on predebridement
      cultures eventually caused infection; 7% of cases with negative predebridement
      cultures became infected. Of cases that did become infected, predebridement
      cultures grew the infecting organism only 22% of the time. Postdebridement
      cultures were more accurate in predicting infection; however, of cases that
      became infected, the infecting organism was present on postdebridement cultures
      only 42% of the time. It is concluded that predebridement and postdebridement
      bacterial cultures from open fracture wounds are of essentially no value, and it
      is recommended that they not be done.

PMID- 9186204
TI  - Autogenous iliac crest bone graft. Complications and functional assessment.
AB  - Functional outcomes and complications experienced by adult patients who underwent
      iliac crest bone grafting were evaluated to assess the effect of bone grafts on
      patient function. In addition to retrospective chart reviews, patients completed
      the Sickness Impact Profile and a detailed questionnaire on pain. One hundred
      ninety-two patients met study inclusion criteria. Major complications were
      recorded in four (2.4%) patients in whom infections developed requiring
      readmission. Thirty-seven (21.8%) patients had minor complications. One hundred
      nineteen of 170 patients were available for followup; of these 119 patients, 87
      (73.1%) returned completed questionnaires. Thirty-three of 87 (37.9%) patients
      reported pain 6 months postoperatively. The incidence of pain decreased with
      time, with 16 of 87 (18.7%) patients continuing to report pain more than 2 years
      postoperatively. Proportionately more spine patients reported pain at all time
      points. The mean Sickness Impact Profile score for patients completing
      questionnaires was nine, suggesting most patients were functioning well 2 years
      postoperatively. The morbidity of iliac crest grafting remains substantial. Pain
      symptoms in this study sample seemed to last longer in more patients than earlier
      series have indicated. Minimizing muscle dissection around donor sites and the
      advent of bone graft substitutes may help alleviate these problems.

PMID- 9186205
TI  - Modified transverse locking nail fixation of proximal femoral fractures.
AB  - It was hypothesized that transverse locking screws of intramedullary nails,
      seated above the lesser trochanter, provide equal strength to that of
      reconstruction nails, and that screws placed through the medial cortex of the
      femoral neck do not have adverse biomechanical effects during physiologic
      loading. Synthetic femurs (n = 10) and paired anatomic specimen femurs (n = 14)
      were tested intact and with an intramedullary device in place. Intact specimens
      were loaded nondestructively, then a segmental subtrochanteric defect was created
      and either a high seated transverse locking nail or a reconstruction nail was
      inserted and statistically locked. Axial and torsional stiffness were determined
      followed by axial failure testing. Mechanical parameters evaluated were
      stiffness, displacement, and energy. The implanted specimens did not show any
      statistically significant difference between transverse or reconstruction screw
      constructs with any of the measured parameters (stiffness, displacement, and
      energy). Failure tests in implanted specimens also did not show any statistically
      significant difference in yield load, yield displacement, or energy to failure
      between implant constructs. All anatomic specimens failed, with fractures of the
      proximal fragment involving medial and lateral cortices. Synthetic specimens did
      not fracture but showed failure with implant deformation at the level of the
      skeletal defect. The use of high seated transverse locking nails for complex
      proximal femoral fractures is a viable option and has comparable in vitro
      mechanical performance with reconstruction nails. Although not shown to be a
      problem in the present study, clinical evaluation of screws through the medial
      femoral neck cortex is required.

PMID- 9186206
TI  - Biomechanics of the hip joint and the effects of fracture of the acetabulum.
AB  - The biomechanical analysis of the normal and arthritic hip joint have been the
      subject of numerous publications in orthopaedics. Biomechanical investigations
      focusing on the effect of fractures of the acetabulum on the alteration of hip
      joint mechanics have been a recent development. This paper outlines currently
      available methodologies for simulating load across the hip, and as measuring
      articular contact and contact stresses. Results of investigations of posterior
      wall fractures and transverse fractures of the acetabulum are presented.
      Directions for future research in the area of mechanical investigations of
      acetabular fractures are discussed.

PMID- 9186207
TI  - Anterior release test. A new test for occult shoulder instability.
AB  - Occult shoulder instability is recognized as a significant contributor to
      shoulder dysfunction in throwing athletes. Diagnosis of occult instability by
      physical examination remains challenging. The anterior release test is a test for
      physical examination of the shoulder. It was developed to facilitate detection of
      occult anterior instability. One hundred shoulders were examined preoperatively
      by the same examiner. Based on surgical findings, the shoulders were classified
      as anterior instability or other. The results of examination were compared with
      the operative findings. Sensitivity was calculated as 91.9%, specificity 88.9%,
      positive predictive value 87.1%, negative predictive value 93.0%, and accuracy
      90.2%. The anterior release test is a reliable and reproducible test for the
      detection of the unstable shoulder.

PMID- 9186208
TI  - Lumbar facet joint infection associated with epidural and paraspinal abscess.
AB  - A case of lumbar facet joint infection associated with abscesses of the
      paraspinal muscles and the epidural space is presented. The infection did not
      respond to intravenous antibiotic therapy and resolved only after incision and
      drainage of the epidural space, involved facet joint, and paraspinal musculature.
      Magnetic resonance imaging, which showed a widened facet joint, epidural abscess,
      and paraspinal involvement, aided in diagnosis and preoperative planning. This
      condition is rare, and this report outlines some clinical characteristics of the
      infection and the usefulness of magnetic resonance imaging in visualizing the
      extent of the infection.

PMID- 9186209
TI  - Survivorship analysis of DKS instrumentation in the treatment of
      spondylolisthesis.
AB  - This retrospective study analyzed the survivorship of DKS instrumentation and the
      clinical outcomes in 185 patients with spondylolisthesis. These patients were
      treated with Zielke DKS instrumentation for a mean followup period of 3.5 years.
      Eight (4.3%) patients had late removal of implants, 25 (14%) had rod breakage,
      three (1.7%) had screw breakage, and 16 (8.7%) had nut loosening. The survivor
      rate of DKS instrumentation was 96% within 3 months after operation, 80% at 2
      years, and 61% at 5 years after surgery. One hundred sixty-three (88%) patients
      had solid posterolateral fusion, and 167 (90%) patients had good to excellent
      results. Adjacent instability developed in 18 (9.7%) patients. Although Zielke
      DKS instrumentation has a smaller rod and relatively insecure locking system
      between the rod and screw, it is an effective implant for the treatment of
      spondylolisthesis.

PMID- 9186210
TI  - Longitudinal evaluation of time related bone remodeling after cementless total
      hip arthroplasty.
AB  - Bone remodeling after cementless total hip arthroplasty was evaluated by dual
      energy x-ray absorptiometry in a longitudinal study of 32 hips. After insertion
      of a fully porous surface anatomic stem made of cobalt chromium, bone mineral
      density was analyzed until at least 2 years postoperatively. Bone remodeling was
      evaluated in terms of regional bone density changes in the seven adjacent
      periprosthetic zones as well as the global change in bone density distribution
      over the entire periprosthetic area. At 12 months after the operation, the
      averaged regional bone mineral density in all seven zones showed a rapid
      decrease, ranging from 9% to 24% of the bone mineral density present at 2 weeks
      postoperatively. Thereafter, the bone density change appeared to be stabilized.
      The global change in the bone density distribution was expressed as two
      summarizing statistical indexes derived from principal component analysis: the
      first index represents the change of average bone mineral density over the entire
      periprosthetic area, and the second represents the severity of bone mineral
      density decrease in the proximal area versus the distal area. The second index
      proved that more bone density reduction occurred in the proximal area, but this
      was variable among patients and correlated significantly with the stem size and
      the initial bone mineral density in the distal part of the periprosthetic area.
      This longitudinal dual energy x-ray absorptiometry study suggests that a large
      part of the bone remodeling after cementless hip arthroplasty ceases within 1
      year postoperatively, and stem size and the initial bone density around the
      distal portion are important considerations for predicting the proximal bone
      density decrease during the early rapid remodeling period.

PMID- 9186211
TI  - Hemodilution with other blood reinfusion techniques in total hip arthroplasty.
AB  - Acute normovolemic hemodilution has been reported to result in blood savings
      varying from 18% to 90%. Very few of these are randomized prospective studies.
      This study attempts to determine the blood transfusion savings if acute
      normovolemic hemodilution is used in combination with autologous predonated blood
      and cell saver. Thirty-three patients undergoing total hip arthroplasty were
      assigned randomly to one of two groups (control, n = 16; hemodilution, n = 17).
      Patients in both groups entered an autologous predonation program if cleared
      medically and were placed on Cell Saver intraoperatively and in the
      postanesthesia care unit. In addition, the hemodilution group underwent acute
      normovolemic hemodilution preoperatively. Only 41% of the patients in the
      hemodilution group required any autologous blood transfusion as compared with 75%
      of the control group. In addition, the hemodilution group required a mean lower
      quantity of autologous blood transfusion (41% of the estimated blood loss) as
      compared with the control group (71%). The net anesthesia time increased by an
      average of 11.4 minutes in the hemodilution group. Acute normovolemic
      hemodilution is a safe procedure even in an older patient population.
      Hemodilution resulted in fewer patients needing autologous predonated blood
      transfusions. The major benefit of hemodilution was seen when predonation was not
      possible.

PMID- 9186212
TI  - Comparative study of total hip arthroplasty between younger and older patients.
AB  - Ten- to 20-year (average, 14 years) results of primary Charnley low friction
      arthroplasties performed in patients 50 years of age or younger (55 sockets and
      53 femoral prostheses) were compared with those in patients older than 50 years
      (273 sockets and 273 femoral prostheses). The incidence of radiologic loosening
      of the socket, including revision cases, was higher in the younger (29.1%) than
      in the older patients (14.3%). The revision rate for aseptic loosening of the
      socket was higher in the younger (20%) than in the older group (4%). This poor
      performance of the socket may be attributable to the higher incidences of
      rheumatoid diseases and accelerated polyethylene wear in the younger patients. In
      contrast, only 3.8% of the femoral prostheses were radiologically loose, and none
      of them were revised in the younger patients. These figures were comparable with
      those in the older patients. Quality of structure of bone available for implant
      fixation may be important for the durability of the arthroplasty. It was
      considered inferior on the acetabular side and better on the femoral side in the
      younger patients than in the older. Continued use of the cemented Charnley
      femoral prostheses can be justified in young patients, although further research
      is required for the socket problem.

PMID- 9186213
TI  - Knee version associated with anterior knee pain.
AB  - Version of the knee in the presence and absence of anterior knee pain was
      evaluated by computed tomography in this study. Version of the knee is defined as
      the static rotation of the tibia with respect to the femur in full knee
      extension. Fourteen patients in whom conservative management for anterior knee
      pain failed were compared with 14 volunteers with no symptoms. Computed
      tomography images of the femoral condyles and tibial plateau were obtained with
      the knee extended. The angle between the bicondylar and posterior tibial axes was
      measured. This angle, representing external rotation of the tibia relative to the
      femur, was increased significantly in patients with symptoms (7 degrees) compared
      with volunteers with no symptoms (1 degree). This increased knee version
      identifies a unique morphologic characteristic of the knee with anterior pain.

PMID- 9186214
TI  - Patellofemoral osteoarthritis after patellar dislocation.
AB  - Clinical and radiographic studies were done for 85 patients treated
      conservatively for acute primary patellar dislocation occurring an average 13
      years (range, 6-26 years) previously. Osteoarthritic changes in the
      patellofemoral joint were evaluated with special reference to the primary
      conservative treatment and treatment of redislocations (operative or
      conservative) or treatment for other subsequent problems such as pain and/or
      subluxations (late surgery). The patients were divided into two groups on the
      basis of findings in the unaffected knee and other joints. There were 56 patients
      (66%) with predisposing factors such as an abnormal quadriceps angle, positive
      apprehension test, quadriceps muscle atrophy, or generalized joint laxity common
      to all patients. Patients with or without predisposing factors did not differ
      from each other in terms of arthritic changes. Patellofemoral joint degeneration
      was found in the affected knee in 19 patients (22%) and in the unaffected knee in
      nine (11%). Conservative treatment without subsequent redislocations resulted in
      osteoarthritic changes in 29% of the cases and in 13% of cases with occasional
      redislocations. Osteoarthritic changes were found in 17% of patients treated
      operatively and in 12% of patients treated conservatively for redislocations. Of
      the patients who underwent late surgery for patellofemoral pain or subluxations,
      35% showed osteoarthritic changes. In general, there were more degenerative
      changes in patients with stable patellae (no redislocations) than in those with
      occasional recurrences, especially in older and heavier patients.

PMID- 9186215
TI  - Radial displacement of the medial meniscus and Fairbank's signs.
AB  - Radial displacement of the medial meniscus in knees that have not undergone
      meniscectomy was measured using magnetic resonance imaging. In age matched
      subjects, the amount of displacement was compared with the presence or absence of
      radiographic signs described by Fairbank. A medial displacement index, defined as
      the ratio of meniscal overhang to meniscal width, was used to quantify meniscal
      displacement. The medial displacement indices for knees with and without
      radiographic signs were 0.45 +/- 0.22 and 0.08 +/- 0.10, respectively (mean +/-
      standard deviation). Differences were highly significant. The greatest meniscal
      displacements were seen in knees with radiographic Fairbank's signs; no knee with
      such signs had an undisplaced meniscus. It is concluded that radiographic signs
      of osteoarthritis known to follow meniscectomy can develop in knees that exhibit
      significant radial displacement of the medial meniscus. Radial displacement may
      be related to loss of meniscal function because the radiographic signs are
      similar to those that follow meniscectomy.

PMID- 9186216
TI  - Psoas over the brim lengthenings. Anatomic investigation and surgical technique.
AB  - Lengthening of the psoas tendon commonly is performed for various conditions of
      the hip including developmental dysplasia and neuromuscular contractures and
      instability. Anecdotal reports of injury to surrounding neurovascular structures
      suggest an investigation of the local anatomy is warranted. Using magnetic
      resonance images from 54 children younger than 10 years, the authors examined the
      anatomic relationship between major neurovascular structures (femoral artery and
      vein, external iliac artery and vein, femoral nerve) and the psoas tendon. The
      mean distance between the neurovascular structures and the psoas tendon in the
      over the brim position is 1 cm, although it may be as close as 4 mm in a child.
      The mean distance is 3.1 cm at the tendon's insertion at the lesser trochanter.
      Surgeons performing psoas over the brim lengthenings should be aware that major
      neurovascular structures may be only 4 mm from the psoas tendon. The recommended
      surgical technique is presented.

PMID- 9186217
TI  - Stride analysis after proximal tibial replacement.
AB  - Ten patients who had undergone primary intraarticular proximal tibial replacement
      between April 1985 and December 1994, and had a minimum of 2 years of followup,
      were available for stride analysis. Mean age, time since intraarticular proximal
      tibial replacement, height, and weight were 23.8 years, 6.5 years, 167 cm, and 63
      kg, respectively. A volunteer control group of five male patients who had
      undergone above knee amputation was obtained from the local community. The mean
      age, time since above knee amputation, height, and weight were 43.6 years, 24.1
      years, 165 cm, and 70 kg, respectively. Stride analysis was performed over the
      central 6-m portion of a 10-m walkway at a self selected, comfortable pace. Gait
      velocity, stride length, cadence, and stance time symmetry were measured.
      Velocity after intraarticular proximal tibial replacement versus above knee
      amputation was 79.2 +/- 7.6 m per minute versus 71.4 +/- 5.4 m per minute.
      Cadence after intraarticular proximal tibial replacement versus above knee
      amputation was 112.4 +/- 10.6 steps per minute versus 110.1 +/- 2.4 steps per
      minute. There were no significant differences between stride length (1.41 +/-
      0.13 m versus 1.43 +/- 0.12 m) and stance time symmetry (0.90 +/- 0.07 versus
      0.87 +/- 0.11) for intraarticular proximal tibial replacement versus above knee
      amputation. The results suggest that endoprosthetic reconstruction resulted in a
      gait comparable with that after above knee amputation with an external
      prosthesis.

PMID- 9186218
TI  - Neuropathic arthropathy caused by paraneoplastic sensory neuropathy. A case
      report.
AB  - Neuropathic arthropathy of both knees after paraneoplastic sensory neuropathy
      developed in a 64-year-old woman. The patient was found to have small cell lung
      cancer 2 months after the onset of a sensory neuropathy that was diagnosed as
      paraneoplastic sensory neuropathy, a nonmetastatic neurologic complication in
      patients with malignancy. The onset of paraneoplastic sensory neuropathy was
      followed by the gradual onset of neuropathic arthropathy. This is the first well
      documented report on neuropathic arthropathy in a patient with paraneoplastic
      sensory neuropathy.

PMID- 9186219
TI  - Bone mineral changes during tibial fracture healing.
AB  - The traditional assessment of fracture healing by manipulation and viewing of
      radiographs is subjective and qualitative. Dual energy x-ray absorptiometry by
      contrast provides an accurate, precise, and minimally invasive quantitative
      measure of bone mineral density, a property that shows strong correlations with
      various mechanical properties of bone. Fourteen patients with unilateral tibial
      shaft fractures stabilized by external fixation were monitored with dual energy x
      ray absorptiometry at monthly intervals after fracture. Fractured and
      contralateral unfractured bones (controls) were scanned on each occasion. Changes
      in mineralization with time over the whole length of the fractured bone could be
      seen. The most pronounced effects were visible in the area of the fracture, with
      a minimum recorded fracture site bone mineral density of 38 +/- 13% of
      contralateral values, but often more long term alterations in bone mineral
      density affected regions at some distance from this zone. Significantly, in four
      patients who had scans 5 or more months after fracture, the mineralization at the
      fracture site had returned to control levels, whereas bone mineral density in a
      region proximal to the fracture showed evidence of persisting posttraumatic
      osteoporosis.

PMID- 9186220
TI  - Irreducible intertrochanteric fractures of the femur.
AB  - A retrospective study during a 3-year interval revealed that four of 112 patients
      had intertrochanteric fractures that were irreducible by the usual closed
      manipulation and traction techniques at the time of surgery. Each of these
      patients' preoperative radiographs showed a fracture line that bisected the
      lesser trochanter and was relatively uncomminuted. Although longitudinal traction
      and appropriate closed manipulation provide acceptable reduction for most
      intertrochanteric fractures, the few with the described fracture pattern may
      require open reduction with removal of interposed soft tissue to achieve
      satisfactory alignment.

PMID- 9186221
TI  - Anatomic basis of lag screw placement in the anterior column of the acetabulum.
AB  - The projection point of the axis of the anterior column of the acetabulum on the
      outer table of the iliac wing was determined in 15 adult bony hemipelves. The
      optimal entry point for lag screw fixation in the anterior column was located 16
      +/- 3.9 mm superior to the midpoint of the line connecting the apex of the
      sciatic notch with the notch between anterior superior iliac spine and anterior
      inferior iliac spine, and 46 +/- 5.9 mm superior to the acetabular rim. The mean
      inclination of the projected axis was 90.6 degrees +/- 5.0 degrees in the
      sagittal plane and 29.0 degrees +/- 4.4 degrees in the transverse plane. These
      data may facilitate insertion of a lag screw into the anterior acetabular column
      and minimize the risk of articular violation or cortical penetration because
      there is a narrow margin of safety. The lag screw placement also may be aided by
      palpating the anterior column with a finger and by intraoperative fluoroscopy for
      visualization of the hip joint and the anterior column in the obturator or pelvic
      outlet views.

PMID- 9186222
TI  - Neutrophil mediated microvascular injury in acute, experimental compartment
      syndrome.
AB  - The purpose of this study was to determine the contribution of neutrophils and
      tissue xanthine oxidase to the skeletal muscle microvascular dysfunction in an ex
      vivo model of acute compartment syndrome. Adult dogs were rendered neutropenic or
      depleted of tissue xanthine oxidase before gracilis muscle isolation. Compared
      with continuously perfused, nonischemic muscles, acute, experimental compartment
      syndrome resulted in a dramatic increase in microvascular permeability, muscle
      neutrophil content, and muscle vascular resistance. Neutropenia prevented,
      whereas xanthine oxidase depletion had no effect on, the microvascular
      dysfunction and muscle neutrophil infiltration elicited by experimental
      compartment syndrome. These results suggest that neutrophils contribute to the
      microvascular dysfunction and blood flow distribution abnormalities elicited by
      acute, experimental compartment syndrome.

PMID- 9186223
TI  - Prosthetic metals interfere with the functions of human osteoblast cells in
      vitro.
AB  - The release of metals from total joint prostheses may contribute to
      periprosthetic bone loss manifested as osteolysis. The effects of titanium,
      cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells)
      were investigated in vitro. Titanium, cobalt, and chromium at concentrations of
      1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and
      injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at
      concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release
      of interleukin-1 beta and tumor necrosis factor-alpha by lipopolysaccharide
      stimulated human osteogenic sarcoma cells, whereas they did not alter the release
      of transforming growth factor-beta 1. Cobalt at concentrations ranging from 0.1
      to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium
      and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml
      significantly inhibited the release of osteocalcin by human osteogenic sarcoma
      cells, whereas titanium had no effect. Titanium, cobalt, and chromium at
      concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type
      I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the
      cell proliferation in response to lipopolysaccharide stimulation, whereas
      titanium did not. The data presented in this article suggest that the metal
      induced disregulation of cytokine release and osteoblast dysfunction may play an
      important role in the induction of osteolysis in patients with total joint
      arthroplasties.

PMID- 9186224
TI  - Effect of cutting the plantar fascia on mechanical properties of the foot.
AB  - A biomechanical model was used to calculate the loadbearing characteristics of
      the plantar fascia and to determine the effect of cutting the plantar fascia on
      the stiffness of the foot. With a load of 683 N applied to the foot, the model
      predicted a 17% increase in vertical displacement and a 15% increase in
      horizontal elongation when the plantar fascia was cut, compared with the
      corresponding value when the plantar fascia was intact. Plantar fasciotomy,
      although clinically satisfactory in cases of recalcitrant heel pain, decreases
      the stiffness of the foot and creates a less rigid and more deformable arch. The
      biomechanical model described can help to evaluate the possible outcome of such a
      procedure.

PMID- 9186225
TI  - Improved fracture healing with less rigid plates. A biomechanical study in dogs.
AB  - The effect of axial plate flexibility on bone healing was investigated with four
      experimental plating systems using elastic inserts to manage their axial
      flexibility in compression. The plates were tested in 72 dogs that underwent
      unilateral femoral osteotomy and noncompression plating on alternate sides. The
      femurs of 18 dogs were plated with each of the four plating systems: six for 8
      weeks, six for 16 weeks, and six 6 for 24 weeks. Each osteotomized femur and its
      contralateral control were removed at the end of the plating periods and tested
      in multidirectional nondestructive bending to evaluate the polar distributions of
      their flexural rigidity. Results from each pair of bones were used to calculate
      parameters defining the relative mechanical status of the healing bone. These
      parameters were used to evaluate the effects of plating system axial flexibility
      and time on healing. It was found that: within the selected range of axial
      flexibility there was an optimal value that produced the best healing; healing
      progressed with a diminishing rate leading to a steady state; and all four
      plating systems produced healing superior to that obtained with dynamic
      compression plates.

PMID- 9186226
TI  - New model for chronic osteomyelitis with Staphylococcus aureus in sheep.
AB  - The purpose of this study was to develop a large animal model for chronic
      osteomyelitis, suitable for toxicologic research and therapeutic intervention
      studies. Osteomyelitis was induced in 52 healthy adult Texel sheep by injecting a
      sclerosing agent and a hemolytic strain of Staphylococcus aureus into the
      proximal tibial marrow cavity. Evaluation was done by clinical, radiologic,
      bacteriologic, and histologic parameters for 3 months. Clinical signs of
      infection consisted of localized soft tissue swelling, pain during the acute
      phase, and limping in all sheep. Radiologic features were moderate to extensive
      periosteal reaction, cortical lysis, mild to extensive new bone formation, and
      frequent development of sequestra limited to the proximal part of the tibia.
      Cultures were positive for the same strain of Staphylococcus aureus in all but
      one sheep. Histology showed chronic active inflammation, osteolysis, new woven
      bone formation, debris, clusters of bacteria, and surrounding granulation tissue.
      It was necessary to administer a single prophylactic dose of antibiotics 1 hour
      after surgery to prevent fatal sepsis. It was concluded that sheep are a suitable
      model for chronic osteomyelitis.

PMID- 9186227
TI  - Morphology and matrix composition during early tendon to bone healing.
AB  - This study outlines the early morphologic phenomenon of tendon to bone healing in
      the rabbit model. Twelve skeletally mature, male New Zealand White rabbits
      received transplantation of the hallucis longus tendon into a 2-mm calcaneal bone
      tunnel. The morphologic characteristics of the healing tendon to bone interface
      were evaluated at 1, 2, 4, and 6 weeks after surgery by the use of conventional
      histology and immunohistochemical localization of collagen Types I, II, and III.
      Histologic analysis illustrated progressive maturation and reorganization of the
      tendon to bone interface with subsequent development of tissue collagen fiber
      continuity between the tendon and bone. Initially, diffuse immunolocalization of
      all three collagen types was observed within the scar tissue filling the space
      between the tendon and bone. During a 6-week period, reorganization of the scar
      tissue into an interface occurred, similar to an indirect insertion. Although a
      definitive fibrocartilage region did not form, Type II collagen was localized at
      the remodeling insertion site throughout the first 6 weeks of repair. In
      addition, Type III collagen fibers, resembling Sharpey's fibers, were noted to
      span this interface. The characterization of the insertion between tendon and
      bone is important to the understanding of healing in commonly used orthopaedic
      grafting procedures, such as anterior cruciate ligament reconstructions.

PMID- 9186228
TI  - Anatomic determinants of first metatarsophalangeal flexion moments in hallux
      valgus.
AB  - A laboratory cadaver model was used to assess the effects of the major anatomic
      components of hallux valgus deformity on first metatarsophalangeal flexion
      moments. The individual components of the flexor hallucis longus' effective
      tendon moment arm were evaluated as a function of imposed hallux valgus, of
      hallux pronation, and of combined hallux valgus and pronation. To simulate the
      effects of distal first metatarsal surgery, the components' changes after
      metatarsal head lateral translation or supination were assessed. Significant
      changes in effective tendon moment arm occurred with increases in the hallux
      valgus angle, with changes in the hallux pronation angle, and with combined
      increases in the hallux valgus angle and hallux pronation angles. The changes
      involved primarily were a redirection of the moment vector's projection within
      the superior and inferior plane or medial and lateral plane, rather than an
      appreciable alteration of the magnitude of the resultant. By contrast, neither
      translational nor rotational displacements of the metatarsal head influenced any
      of the individual components of the effective tendon moment arm.

PMID- 9186229
TI  - A curriculum for the ideal orthopaedic residency. Academic Orthopaedic Society.
AB  - The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in
      orthopaedics. The members developed an approach using the Delphi system to define
      and obtain consensus on the characteristics of the ideal residency. Six
      categories of educational attributes were included: General; Clinical Management;
      Skills and Technical Aspects; Rehabilitation; Basic Science and Research; and
      Educational Environment. The following year a questionnaire was sent to more than
      125 programs in an attempt to have residents and staff anonymously self score
      their residencies according to the standards defined by the Delphi panels. The
      results obtained from the 745 responders from 73 programs validate effectively
      the characteristics of the ideal program and also show the variation among the
      programs.

PMID- 9186230
TI  - Painful mass adjacent to the tibial tubercle of a 14-year-old boy. Periosteal
      osteosarcoma.

PMID- 9186231
TI  - Evaluation of collagen ceramic composite graft materials in a spinal fusion
      model.

PMID- 9186232
TI  - Differential diagnosis, causes, and management of hypercalcemia.

PMID- 9186233
TI  - Ipsilateral median somatosensory evoked potentials recorded from human
      somatosensory cortex.
AB  - Somatosensory evoked potentials (SEP) to ipsilateral and contralateral median
      nerve stimulations were recorded from subdural electrode grids over the
      perirolandic areas in 41 patients with medically refractory focal epilepsies who
      underwent evaluation for epilepsy surgery. All patients showed clearly defined,
      high-amplitude contralateral median SEPs. In addition, four patients showed
      ipsilateral SEPs. Compared with the contralateral SEPs, ipsilateral SEPs were
      very localized, had a different spatial distribution, were of considerably lower
      amplitude, had a longer latency (1.2-17.8 ms), did not show an initial
      negativity, and were markedly attenuated during sleep. Stimulation of the
      subdural electrodes overlying the sensory hand area was associated with
      contralateral hand paresthesias, but no ipsilateral hand paresthesias, occurred.
      It was concluded that subdurally recorded cortical SEPs to ipsilateral
      stimulation of the median nerve (M) reflect unconscious sensory input from the
      hand possibly serving fast bimanual hand control. The anatomical pathway of these
      ipsilateral short-latency MSEPs is not yet known. Transcallosal transmission
      seems unlikely because of the short delay between the ipsilateral and
      contralateral responses in selected cases. The infrequent occurrence of
      ipsilateral subdurally recorded SEPs and their low amplitude and limited
      distribution suggest that they contribute very little to the short-latency
      ipsilateral median SEPs recorded on the scalp.

PMID- 9186234
TI  - Event-related coherence and event-related desynchronization/synchronization in
      the 10 Hz and 20 Hz EEG during self-paced movements.
AB  - To investigate the activity of cortical regions in the control of movement, we
      studied event-related desynchronization/synchronization (ERD/ERS), event-related
      coherence (ERC), and phase coherence in 29-channel EEGs from 9 subjects
      performing self-paced movements of the right index finger. Movement preparation
      and execution produced ERD over the sensorimotor areas at 10 Hz and 20 Hz,
      followed by ERS. ERD corresponded spatiotemporally to an increase in coherence
      over the frontocentral areas. For both frequency bands, ERD began over the left
      sensorimotor areas and became bilateral at the time of movement onset. The
      coherence increase with frontal areas began in the left central areas and became
      symmetrical after EMG onset. The ERD and coherence increase was longer at 10 Hz
      than at 20 Hz. Phase coherence at 10 Hz showed a lead of anterior regions to
      posterior regions throughout the time period, and at 20 Hz showed a tendency
      toward zero phase delay corresponding with the movement. EEG desynchronization
      parallels functional coupling over sensorimotor and frontal areas. Event-related
      coherence and phase coherence findings implicate the frontal lobes in control of
      movement planning and execution. The involvement of different frequency bands
      with different timings may represent parallel changes in the cortical network.

PMID- 9186235
TI  - Safety of rapid-rate transcranial magnetic stimulation: heart rate and blood
      pressure changes.
AB  - We examined the influence of rapid-rate transcranial magnetic stimulation on
      heart rate and blood pressure in 13 healthy volunteers. In a first series three
      different cortical magnetic stimuli were applied: over C3, C4 and Fz (10/20
      system), in a second series additionally over Pz. We also used a stimulus over
      the brachial plexus and a sham stimulus. Five stimuli of each location were
      applied with a Cadwell high speed magnetic stimulator using a focal point
      circular coil. Stimulus train duration was 500 ms, stimulus frequency 20 Hz.
      Stimulus strength was 70-90% of maximum stimulator output, 20% of maximum
      stimulator output above subjects' individual motor threshold. The subjects
      assessed stimulus inconvenience immediately after stimulation. ECG and blood
      pressure (Finapres) were recorded continuously during the 1 h test. In all
      subjects there was a clearly marked autonomic response with heart rate
      acceleration and decrease in blood pressure after all stimuli. There was no
      difference in responses between cortical stimuli. Blood pressure decrease after
      sham stimulation was significantly smaller than after cortical stimulation, it
      was more marked after brachial plexus stimulation. Autonomic reaction correlates
      well with subjective estimation of stimulus inconvenience. We conclude the
      observed effect of rapid-rate transcranial magnetic stimulation to be associated
      to rather an unspecific arousal reaction than to a direct stimulation of
      autonomic cortex areas. We did not observe any clinically relevant side-effects.

PMID- 9186236
TI  - Event-related potentials to Italian spoken words.
AB  - Forty-four right-handed volunteers were invited to listen to Italian 5-letter
      words of different kinds, including non-words, digitally recorded. Signals from
      16 electrodes were averaged and displayed both as traces and maps. When the same
      word was monotonously delivered to the subject, a positive component at 340 ms
      was recorded following the N100-P200 complex. This potential was automatic,
      phonologically driven, independent of habituation, specific for verbal material
      and lateralized to the left side. By contrast semantic tasks evoked bilateral
      N400, by using the oddball paradigm with different kinds of target stimuli,
      including non-words. The N400 duration was related to the task complexity. The
      late positive component was locked-in-time with the end of the words. Therefore,
      N400 reached its peak before the word completion. At that time the probability of
      recognition was 60%, progressively reaching 100% at the time of the late positive
      component. Intra- and interindividual variance was low. The findings indicates
      two different language processings: one is confined to the perisylvian regions of
      the left hemisphere in right-handed subjects and appears earlier, reflecting
      phonological processing, whereas the other one is bilateral and takes places when
      semantic judgments are going on. Event-related potentials during language
      processing appear to be a very useful tool, especially when EEG maps are
      displayed, giving us the information on both temporal and spatial events.

PMID- 9186237
TI  - Brain/behaviour dissociation on old/new distinction in a patient with amnesic
      syndrome.
AB  - Event-related potentials (ERP) were recorded in a recognition memory task in 5
      healthy subjects and an amnesic patient. A list of high-imagery words with low
      probability in everyday language was presented visually for 200 ms each. A second
      list, consisting of 50% previously presented ('old') words and 50% 'new' words
      was presented immediately after the first list. Old/new distinction was
      determined by the subject's motor response. For each subject single trial
      analysis of ERPs was performed. In each healthy subjects, correct old/new
      distinction was associated with significant ERP differences from 500 to 900 ms
      after stimulus onset. It was, therefore, assumed that task and recording
      procedures were appropriate for the study of ERPs with recognition memory. The
      main finding is a dissociation between brain activity and behaviour with old/new
      distinction in the patient with amnesic syndrome. Frequently, the patient
      incorrectly classified previously shown words ('old' words) to be presented for
      the first time ('new'). But ERP showed that brain processing of 'old' words which
      had incorrectly been classified to be 'new' is different from correctly
      classified new words. ERP differences were significant between 900 and 1200 ms
      after stimulus presentation. These data indicate preserved memory functions which
      are not assessed at the behavioural level in the memory recognition task.

PMID- 9186238
TI  - A topographical ERP study of healthy premature 5-year-old children in the
      auditory and visual modalities.
AB  - The aim of this research is to study the impact of extreme prematurity on the
      cognitive development of the child as assessed at age 5 years 9 months. Our
      samples include 15 healthy prematures born between 25 and 28 weeks of gestational
      age carefully matched with 15 full-term controls. In the first experiment, two
      different auditory stimuli were presented to the subjects who listened passively
      without instruction. The second experiment consisted of a standard visual oddball
      task in which the subjects were instructed to 'catch' two different animals, by
      pushing a left or right button for a moose (n = 120) or a raccoon (n = 40),
      respectively. In the auditory task, 3 ERP peaks were analyzed (frontal N100 and
      P3a, temporal P2). All premature children demonstrated normal early frontal N100
      and temporal P2 responses. The group differences were apparent in the late
      positivity (P3a) where controls showed a larger amplitude to the rare tones
      applied evenly to both ears. In contrast, the prematures did not show sensitivity
      to rare tones but showed a larger P3a upon left ear stimulation, when compared to
      the right. Also, the ERPs to the visual oddball task showed normal early
      positivities (P250-300) in the premature group. Once again, deviations from the
      normal were evident in late waves. The ERPs recorded from prematures showed a
      more diffuse topography especially between 500 and 600 ms post-stimulus and
      around the posterior area (P550). The succeeding negativity (SW) was not altered
      in the premature group. The ERP data suggest that premature children, even
      without clinically apparent problems, convey specific ERP singularity when
      engaged in a task that involves complex processing.

PMID- 9186239
TI  - EEG and ERP assessment of normal aging.
AB  - EEG was recorded from 120 normal adult subjects who ranged in age from 20 to 80+
      years in separate eyes open/closed conditions. The P3(00) event-related brain
      potential (ERP) was elicited with auditory and visual stimuli in separate
      conditions in the same subjects. Spectral analysis indicated that overall EEG
      power decreased as subject age increased. P3 amplitude decreased and peak latency
      increased for both the auditory and visual stimulus conditions as subject age
      increased. Few age-related differences were observed for the N1, P2, or N2
      components. Spectral power from the delta, theta, and alpha bands correlated
      positively with P3 amplitude across subject age, but mean band frequency
      demonstrated only weak associations with P3 latency. No strong relationships were
      found between EEG and the other ERP component variables. The results suggest that
      age contributes to EEG power shifts, and that such changes significantly affect
      age-related variability of the P3 ERP component.

PMID- 9186240
TI  - The cortical generators of the contingent negative variation in humans: a study
      with subdural electrodes.
AB  - Contingent negative variations (CNVs) and Bereitschaftspotentials (BPs) were
      recorded from subdural electrodes implanted in 14 patients with intractable
      epilepsy. For recording CNVs, a Go/NoGo S2 choice reaction-time paradigm was
      employed. Two seconds after presentation of a low tone burst (S1), either a
      medium (S2m) or a high tone burst (S2h) was delivered at random. Patients were
      instructed to make middle finger extensions after S2m but not after S2h. For
      recording BPs, patients repeated self-paced middle finger extensions. BPs were
      recorded from the primary motor area (MI), the primary sensory area (SI) and the
      supplementary sensorimotor area (SSMA). CNVs showed a patchy distribution in the
      prefrontal area and SSMA for the early component and in the prefrontal area, MI,
      SI, temporal area, occipital area and SSMA for the late component. These results
      suggest that the CNV recorded from the scalp is the summation of multiple
      cortical potentials which have different origins and different functions. The
      cortical distribution of the late CNVs was different from that of BPs. Late CNVs
      are not equivalent to BPs and are not related to motor preparation alone. After
      S2, 3 kinds of potentials, probably related to decision making, somatosensory
      feedback and motor execution under specific conditions, respectively, were
      observed.

PMID- 9186241
TI  - Ozone produces functional deficits in the rat visual pathway.
AB  - The effects of ozone (O3) have been studied mainly in reference to the
      respiratory pathways, though some reports have shown that this gas produces
      noxious effects in brain. The aim of the present work was to study the O3 effects
      on the central nervous system, focusing on the visual pathway by means of visual
      evoked potentials technique recording in the visual cortex and the lateral
      geniculate nucleus of rats exposed to three different concentrations of O3 (0.75,
      1.5 and 3.0 ppm). Our results showed that P1, N1 and P2 components were
      significantly delayed in the visual cortex and lateral geniculate nucleus in
      those rats exposed to 3.0 ppm of O3. Moreover, the N1 component in the visual
      cortex was also affected even under exposure to 1.5 ppm of O3. Results suggest
      that O3 exposure affects the conduction mechanisms and synaptic excitability of
      the visual pathway. It is known that inhalation of O3 produce a cascade of
      ozonation products capable of producing lipid peroxidation in the brain.
      Unevenness of some neurotransmitters has also been referred in animals exposed to
      this gas. Thus we consider that the delay found in the primary components of the
      visual evoked potentials could obey to a neurochemical disorder produced by O3
      inhalation.

PMID- 9186242
TI  - Visual evoked potentials in the vicinity of the optic tract during stereotactic
      pallidotomy.
AB  - We recorded visual evoked responses in eight patients with Parkinson's disease,
      using a depth electrode either at or below the stereotactic target in the ventral
      part of the globus pallidus internus (GPi), which is located immediately dorsal
      to the optic tract. Simultaneously, scalp visual evoked potentials (VEPs) were
      also recorded from a mid-occipital electrode with a mid-frontal reference
      electrode. A black-and-white checkerboard pattern was phase reversed at 1 Hz;
      check size was 50 min of arc . Pallidal VEPs to full field stimulation showed an
      initial positive deflection, with a latency of about 50 ms (P50), followed by a
      negatively with a mean latency of 80 ms (N80). The mean onset latency of P50 was
      about 30 ms. P50 and N80 were limited to the ventralmost of the GPi and the ansa
      lenticularis. Left half field stimulation evoked responses in the right ansa
      lenticularis region while right half field stimulation did not, and vice versa.
      These potentials thus seemed to originate posterior to the optic chiasm. The
      scalp VEPs showed typical triphasic wave forms consisting of N75, P100 and N145.
      The location of the recording electrode in the ansa lenticularis region did not
      modify the scalp VEP. These results suggest that P50 and N80 are near-field
      potentials reflecting the compound action potentials from the optic tract.
      Therefore, N75 of the scalp VEPs may represent an initial response of the striate
      cortex but not of the lateral geniculate nucleus.

PMID- 9186243
TI  - New measures of outcome needed for the surgical treatment of epilepsy.

PMID- 9186244
TI  - Effects of valproate, phenytoin, and MK-801 in a novel model of epileptogenesis.
AB  - PURPOSE: We have developed and characterized a novel model of epileptogenesis
      based on the convulsive actions of flurothyl in mice. The hallmark feature of
      this model is a reliable change in the type of seizure expressed in response to
      flurothyl from generalized clonic to generalized tonic seizures. The purpose of
      our study was to evaluate the effects of chronic administration of valproate
      (VPA), phenytoin (PHT), and MK-801 on the change in seizure phenotype observed in
      our model system. METHODS: Male C57BL/6J mice received flurothyl seizures on 8
      consecutive days. Two hours after the last generalized seizure, chronic drug or
      vehicle was administered twice daily at 12-h intervals for 28 days. The drugs
      evaluated were VPA (250 mg/kg), PHT (30 mg/kg), and MK-801 (0.5 mg/kg). After a 7
      day drug washout period, mice were retested with flurothyl. RESULTS: Among
      uninjected or vehicle-injected control mice, there was a significant increase in
      the proportion of animals expressing tonic seizures after the 28-day stimulation
      free interval. Chronic administration of VPA or MK-801, but not PHT, blocked the
      characteristic change in seizure type from clonic to tonic. CONCLUSIONS: The
      change in seizure phenotype observed after exposure to our paradigm indicates a
      fundamental reorganization in the propagation of flurothyl-initiated seizures. As
      in electrical kindling, VPA and MK-801 are effective at blocking or retarding the
      reorganization, whereas PHT is not. The concordance in pharmacologic profiles
      between kindling and our model suggests that the processes underlying changes in
      seizure susceptibility in these two models share mechanisms in common.

PMID- 9186245
TI  - Familial Unverricht-Lundborg disease: a clinical, neurophysiologic, and genetic
      study.
AB  - PURPOSE: Progressive myoclonus epilepsies (PMEs) are a clinically and
      etiologically heterogeneous group of disorders. The authors report clinical,
      neurophysiological, and genetic findings of a family from Southern Italy with
      three members affected with PME. METHODS: All data about familial and personal
      antecedents, clinical history, neurologic examination, laboratory tests,
      neurophysiological findings, brain imaging studies, and DNA analysis were
      examined. RESULTS: All results were compatible with the features of Unverricht
      Lundborg disease and patients were homozygous for the "Finnish" ancestral
      haplotype. CONCLUSIONS: Work is in progress to identify and characterize the
      common EPM1 mutation in the Finnish patients. Subsequently, it will be possible
      to verify the hypothesis on the existence of a common mutation in the Finnish
      patients and the Italian family under study, or even in other Mediterranean EPM1
      families.

PMID- 9186246
TI  - Intracranial EEG substrates of scalp ictal patterns from temporal lobe foci.
AB  - PURPOSE: To determine the intracranial EEG features responsible for producing the
      various ictal scalp rhythms, which we previously identified in a new EEG
      classification for temporal lobe seizures. METHODS: In 24 patients, we analyzed
      simultaneous intracranial and surface ictal EEG recordings (64 total channels)
      obtained from a combination of intracerebral depth, subdural strip, and scalp
      electrodes. RESULTS: Four of four patients with Type 1 scalp seizure patterns had
      mesial temporal seizure onsets. However, discharges confined to the hippocampus
      produced no scalp EEG rhythms. The regular 5- to 9-Hz subtemporal and temporal
      EEG pattern of Type 1a seizures required the synchronous recruitment of adjacent
      inferolateral temporal neocortex. Seizure discharges confined to the mesiobasal
      temporal cortex produced a vertex dominant rhythm (Type 1c) due to the net
      vertical orientation of dipolar sources located there. Ten of 13 patients with
      Type 2 seizures had inferolateral or lateral, temporal neocortical seizure
      onsets. Initial cerebral ictal activity was typically a focal or regional, low
      voltage, fast rhythm (20-40 Hz) that was often associated with widespread
      background flattening. Only an attenuation of normal rhythms was reflected in
      scalp electrodes. Irregular 2- to 4-Hz cortical ictal rhythms that commonly
      followed resulted in a comparably slow and irregular scalp EEG pattern (Type 2a).
      Type 2C seizures showed regional, periodic, 1- to 4-Hz sharp waves following
      intracranial seizure onset. Seven patients had Type 3 scalp seizures, which were
      characterized by diffuse slowing or attenuation of background scalp EEG activity.
      This resulted when seizure activity was confined to the hippocampus, when there
      was rapid seizure propagation to the contralateral temporal lobe, or when
      cortical ictal activity failed to achieve widespread synchrony. CONCLUSIONS: Type
      1, 2, and 3 scalp EEG patterns of temporal lobe seizures are not a reflection of
      cortical activity at seizure onset. Differences in the subsequent development,
      propagation, and synchrony of cortical ictal discharges produce the
      characteristic scalp EEG rhythms.

PMID- 9186247
TI  - Abnormal cortical activation during planning of voluntary movement in patients
      with epilepsy with focal motor seizures: event-related desynchronization study of
      electroencephalographic mu rhythm.
AB  - PURPOSE: The spatiotemporal distribution of EEG mu rhythm desynchronization was
      analyzed in patients with partial epilepsy to determine whether frequent focal
      motor seizures could induce a change of cortical activation during the planning
      of a voluntary movement. METHODS: The event-related desynchronization (ERD) of
      the mu rhythm was quantified during a self-paced voluntary movement of the thumb.
      The results were compared between two groups of patients with epilepsy: in one
      group (n = 12), the patients had frontal lobe epilepsy with frequent focal motor
      seizures (FMS); in the second group (n = 12), they had temporal lobe epilepsy
      (TLE) with complex partial seizures but no ictal movement disorder. The results
      were also compared with those of control subjects of same age (n = 10). RESULTS:
      In the control group, desynchronization of mu rhythm began over the contralateral
      central region 2,000 ms before the movement onset. In the FMS group, the
      desynchronization of mu rhythm was delayed, appearing only 500 ms before the
      movement onset, and the amplitude of ERD was increased over the frontocentral
      region. In the TLE group, the spatiotemporal pattern of ERD was the same as in
      normal subjects, but the amplitude of ERD was increased. CONCLUSIONS: These
      results indicate that there is a change of reactivity of mu rhythm in patients
      with partial epilepsy. The change in spatiotemporal pattern of ERD in patients
      with frequent focal motor seizures suggests that there is an abnormal cortical
      activation during the planning of a voluntary movement.

PMID- 9186248
TI  - Persistence of photosensitivity.
AB  - PURPOSE: One hundred patients with photosensitive epilepsy were investigated as
      part of an ongoing follow-up study. Average duration of follow-up was 14 years;
      mean age at follow-up was 27 years. METHODS: All patients were EEG investigated
      using a standard technique of intermittent photic stimulation (IPS). The presence
      of a photoparoxysmal response (PPR) or a degraded PPR indicated the presence of
      photosensitivity. RESULTS: Seventy-seven patients became seizure free. Of the
      untreated patients, photosensitivity disappeared in 14 patients but was present
      in 32 patients. Of the patients who were treated, 31 showed evidence of PPRs or
      degraded PPRs, but 23 patients no longer showed evidence of photosensitivity.
      Thirty-two mothers had 67 children during the follow-up period. Thirteen have so
      far proved to be sensitive to IPS in the laboratory and four have also had
      photosensitive seizures induced in the outside environment. Nine of the children
      have been found not to be photosensitive nor have they had seizures. CONCLUSIONS:
      This study suggests that photosensitivity persists in at least two thirds of
      patients with photosensitive epilepsy and that valproate is effective in
      controlling this photosensitivity.

PMID- 9186249
TI  - Resection of frontal encephalomalacias for intractable epilepsy: outcome and
      prognostic factors.
AB  - PURPOSE: Because focal encephalomalacia is an important cause of medically
      intractable partial epilepsy and few studies have evaluated the efficacy and the
      safety of resecting focal-encephalomalacias to improve seizure control, we
      studied a cohort of 17 consecutive patients who underwent resection of
      encephalomalacias in the frontal lobes as a treatment of their intractable
      epilepsy. METHODS: We evaluated several factors for their value in predicting
      postsurgical seizure control. Pre- and postsurgical magnetic resonance imaging
      (MRI) scans were reviewed independently by 2 blinded investigators. RESULTS: At a
      median of 3 years of follow-up (range 0.6-7.5 years), 12 patients (70%) were
      seizure-free or had only rare seizures. The presence of a focal fast frequency
      discharge (focal ictal beta pattern) at the beginning of seizures on scalp EEG
      was predictive of seizure-free outcome (p = 0.017), even among patients who had
      complete resection of their encephalomalacias (p = 0.016). There was no
      significant differences in outcome with regard to age at the time of the injury
      that caused encephalomalacia, interval between injury and onset of seizures,
      duration of presurgical seizure history, presurgical seizure frequency, age at
      surgery, or the completeness of encephalomalacia resection. The analysis
      regarding completeness of encephalomalacia resection almost reached significance,
      suggesting that it may also be an important predictive factor (p = 0.051).
      CONCLUSIONS: We conclude that surgery is a very effective treatment for
      intractable frontal lobe epilepsy (FLE) secondary to encephalomalacias. Patients
      are more likely to become seizure-free if they have a focal ictal beta discharge
      on their scalp EEG. Complete resection of the encephalomalacia should be
      attempted, since our results suggest that this may be a favorable predictive
      factor. Moreover, the operative strategy for our patients entailed, whenever
      possible, complete resection of the encephalomalacias and of the adjacent
      electrophysiologically abnormal tissues.

PMID- 9186250
TI  - Multiple subpial transection for control of epileptic seizures: effectiveness and
      safety.
AB  - PURPOSE: To assess the efficacy and safety of multiple subpial transection (MST),
      a new technique in epilepsy surgery, alone and in combination with resection.
      METHODS: MST was performed in 22 patients with intractable epilepsy, 10 of whom
      were treated with a combination of a resection and MST in functionally important
      cortex, 6 of whom were treated with a combination of a resection and MST
      performed outside functionally important cortex, and 6 of whom were treated with
      MST alone. RESULTS: Of the 6 patients who received MST alone, none became seizure
      free and 4 showed > 50% reduction of all seizure types. In 2 patients, including
      1 with Rasmussen's encephalitis, no change in seizure frequency or intensity
      occurred. Of the 16 patients in whom MST was combined with a resection, 9 (56%)
      became seizure free. Six of the remaining 7 patients showed > 95% reduction of
      all seizure types. Disappearance of epileptiform potentials in the postoperative
      EEG correlated significantly with complete relief from seizures. Subtle,
      permanent neurological deficits remained in 5 of 14 patients who received MST in
      functionally important brain areas. CONCLUSIONS: Reduction of the seizure
      frequency was substantial in 4 of 6 patients who received MST alone, but complete
      seizure control was not observed. MST surrounding a lesionectomy may be a new
      surgical approach which would minimize the excised volume and improve seizure
      control.

PMID- 9186251
TI  - Factors associated with work outcome after anterior temporal lobectomy for
      intractable epilepsy.
AB  - PURPOSE: Whereas the effect of anterior temporal lobectomy on seizure frequency
      is well recognized, less is known about its impact on work status. METHODS: One
      hundred thirty-four of 190 consecutive patients with temporal lobectomy
      participated in this study. Eligibility criteria were developed to ensure that
      only patients with the potential of achieving specific outcomes were included in
      the corresponding analyses. RESULTS: After surgery, significantly more patients
      were independent in activities of daily living (p < 0.001) or able to drive (p <
      0.001). Income from work also increased (p < 0.01). Nearly one fifth of the
      patients who were eligible for analysis had either a gain (8%) or a loss (11%) of
      full- or of part-time work. Univariate analyses revealed the following factors to
      be associated with full-time work after surgery: student or full-time work within
      a year before surgery, full-time work experience before surgery, full- or part
      time employment experience before surgery, no disability benefits before surgery,
      low postsurgical seizure frequency, improved postsurgical seizure control,
      excellent postsurgical seizure control, driving after surgery, and further
      education after surgery (p < 0.05). Significant factors on multivariate analysis
      were being a student or having full-time work within a year before surgery [odds
      ratio, 16.2 (95% CI, 4.3-60.5)], driving after surgery [15.2 (3.2-72.0)], and
      obtaining further education after surgery [9.2 (2.2-53.0)]. CONCLUSIONS: Anterior
      temporal lobectomy for intractable epilepsy improves activities of daily living
      and the ability to drive. Work outcome of this surgery is influenced by
      presurgical work experience, successful postsurgical seizure control especially
      to allow driving, and obtaining further education after surgery.

PMID- 9186252
TI  - Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe
      epilepsy: changes after treatment with controlled-release carbamazepine.
AB  - PURPOSE: To define sleep disturbances in patients with temporal lobe epilepsy
      (TLE) and explore the association between carbamazepine (CBZ) therapy, sleep, and
      daytime somnolence. METHODS: We recorded nocturnal polysomnography and measured
      subjective and objective daytime somnolence in a group of newly diagnosed TLE
      patients, who had no evidence of anatomic brain lesion on neuroimaging and had
      never been treated before. Recordings were performed at baseline, after the
      initial administration of 400 mg CBZ-controlled release (CR) and after 1 month of
      treatment (400 mg twice daily b.i.d.). The findings were compared with those of a
      group of young healthy volunteers, both at baseline and after the first
      administration of CBZ. The chronic effect of CBZ-CR treatment was evaluated only
      in TLE patients. RESULTS: At baseline, nocturnal sleep patterns of TLE patients
      did not show marked alterations when the influence of seizures, cerebral lesions,
      and drugs had been ruled out. In both the TLE and the control groups, initiation
      of CBZ therapy provoked a reduction and a fragmentation of rapid eye movement
      (REM) sleep and an increase in the number of sleep stage shifts. In the TLE
      group, these effects were almost completely reversed after 1 month of treatment,
      and no significant difference was noted between baseline condition and long-term
      follow-up. With regard to daytime sleepiness, initial administration of the drug
      caused an increase in objective sleepiness only in the control group. Subjective
      sleepiness was higher in the control group than in the TLE group but was not
      modified by the drug. CONCLUSIONS: We conclude that CBZ-CR has negative effects
      on REM sleep during initial administration but chronic treatment does not
      significantly modify nocturnal sleep or daytime somnolence.

PMID- 9186253
TI  - A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo
      parameters of hepatic microsomal enzyme induction and on the kinetics of steroid
      oral contraceptives in healthy female volunteers.
AB  - PURPOSE: This study was conducted to determine whether vigabatrin affects in vivo
      indices of hepatic microsomal enzyme activity and the pharmacokinetics of steroid
      oral contraceptives in healthy subjects. METHODS: Under double-blind conditions,
      13 female healthy volunteers received, in random order and with a washout
      interval of > or = 4 weeks, two oral 4-week treatments with vigabatrin (VGB)
      (maintenance dosage, 3,000 mg daily) and placebo, respectively. The clearance and
      half-life of antipyrine (a broad marker of drug oxidation capacity), the urinary
      excretion of 6-beta-hydroxycortisol (a selective marker of cytochrome CYP3A
      mediated oxidation), and the activity of serum gamma-glutamyltransferase (a
      nonspecific index of microsomal enzyme activity) were determined after 3 weeks of
      each treatment. The single-dose kinetics of a combined oral contraceptive
      containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel were
      also determined after 3 weeks of treatment by specific radioimmunologic assays.
      RESULTS: VGB treatment had no influence on antipyrine clearance (28 +/- 5.6 vs.
      30 +/- 4.5 ml/h/kg on placebo), antipyrine half-life (15.5 +/- 3.5 vs. 14.1 +/-
      2.1 h), urinary 6-beta-hydroxycortisol excretion (488 +/- 164 vs. 470 +/- 228
      nmol/ day), 6-beta-hydroxycortisol-to-cortisol concentration ratio (6.8 +/- 3.1
      vs. 6.1 +/- 3.1) and serum gamma-glutamyltransferase activity (12 +/- 3 vs. 11 +/
      3 IU/L). No difference in pharmacokinetic parameters between VGB and placebo
      sessions were found for ethinyl estradiol (half-life, 12.5 +/- 3.2 vs. 13.9 +/-
      3.2 h; AUC, 874 +/- 301 vs. 939 +/- 272 ng/ L/h) and levonorgestrel (half-life,
      17.7 +/- 5.2 vs. 23.1 +/- 9.8 h; AUC, 27.5 +/- 9.6 vs. 30.0 +/- 12.0
      micrograms/L/h). Two subjects, however, showed a 50 and a 39% reduction in
      ethinyl estradiol AUC during VGB treatment. CONCLUSIONS: At therapeutic dosages,
      VGB did not modify in vivo indices of hepatic microsomal enzyme activity and did
      not interfere significantly with the CYP3A-mediated metabolism of ethinyl
      estradiol and levonorgestrel. Based on these data, VGB is unlikely to affect
      consistently the efficacy of steroid oral contraceptives or interact
      pharmacokinetically with drugs that are eliminated mainly by oxidative pathways,
      particularly those involving cytochrome CYP3A.

PMID- 9186254
TI  - Social adjustment and competence 35 years after onset of childhood epilepsy: a
      prospective controlled study.
AB  - PURPOSE: To study the effect of childhood-onset epilepsy without other neurologic
      deficit on adult social adjustment and competence. METHODS: Social competence was
      studied in a prospective, population-based cohort of childhood-onset epilepsy
      after a mean follow-up of 35 years. One hundred patients (60% of the total
      cohort) had no other neurologic problems ("epilepsy only"), and for each patient,
      two matched controls, a "random" control and an "employee" control were chosen.
      RESULTS: Good social outcome was significantly reduced in the "epilepsy only"
      cohort compared with random controls: education [cumulative odds ratio (COR),
      2.4; 95% confidence interval (CI), 1.4-4.1]; employability (COR, 7.3; 95% CI, 2.7
      20.0); and marriage rate (COR, 3.7; 95% CI, 1.9-7.3). The patients with epilepsy
      rated their own ability to control their lives as "poor or missing" four times
      more frequently than the employee controls. Patients receiving antiepileptic
      polytherapy, but not monotherapy, were significantly less satisfied with their
      present life (OR, 6.7; 95% CI, 1.9-24.1) and felt their general health was
      significantly poorer (OR, 5.1; 95% CI, 1.2-21.3) than did the employee controls.
      Furthermore, patients with continuing seizures were significantly less satisfied
      with their present life (OR, 4.1; 95% CI, 1.1-15.1) than were employee controls.
      CONCLUSIONS: Many patients with "epilepsy only" beginning in childhood have
      persistent and significant social-adjustment and competence problems in
      adulthood.

PMID- 9186255
TI  - Comparative epidemiology of epilepsy in Pakistan and Turkey: population-based
      studies using identical protocols.
AB  - PURPOSE: To determine comparative prevalence rates, demographics, phenomenology,
      seizure classification, presumptive etiology, treatment status, and selected
      socioanthropological aspects of epilepsy in Pakistan and Turkey. METHODS: A
      population-based, cross-cultural comparative study of epilepsy was designed with
      identical protocols to be performed simultaneously in Pakistan and Turkey. The
      essential feature of the design was an unselected population, with reference to
      their previous medical contact, and use of standardized International Community
      Based Epilepsy Research Group (ICBERG) protocols to assess cross-cultural
      differences. RESULTS: In all, 24,130 persons in Pakistan and 11,497 persons in
      Turkey (both urban and rural, of all ages and both sexes) were studied. The crude
      prevalence rate of epilepsy was 9.98 in 1,000 in Pakistan and 7.0 in 1,000 in
      Turkey (14.8 in 1,000 in rural and 7.4 in 1,000 in urban areas of Pakistan; 8.8
      in 1,000 in rural and 4.5 in 1,000 in urban areas of Turkey). In both countries,
      epilepsy was twice as prevalent in rural areas than in urban areas. Mean age of
      onset of epilepsy was 13.3 years in Pakistan and 12.9 years in Turkey. Overall
      frequency of seizure types was similar in both countries, with no urban/rural
      differences. The frequency distribution in Pakistan and Turkey, respectively, was
      as follows; generalized tonic-clonic, 80.5 and 65.4%; simple partial, 5 and 7.4%;
      complex partial, 5 and 12.3%; generalized absence, 0.8 and 4.9%; tonic and
      atonic, 5.8 and 3.7% each; and myoclonic, 5.8 and 1.2%. A putative cause for the
      epilepsy could be attributed in 38.4% of cases in Pakistan and 35.7% of cases in
      Turkey. Only 3% of patients in Pakistan, but 71% of patients in Turkey, believed
      that their illness was due to supernatural causes. The treatment status was very
      poor. In Pakistan, 27.5% of people with epilepsy in urban areas and 1.9% of
      people with epilepsy in rural areas were receiving antiepileptic drugs (AEDs) at
      the time of the survey. In, Turkey 30% of patients were receiving AEDs
      (marginally higher in rural areas). CONCLUSIONS: The prevalence of epilepsy is
      slightly higher in Pakistan than in Turkey; some marginal differences in age and
      sex distribution, are not statistically significant. The results are comparable
      to those in Ecuador, where the same epidemiologic protocol was used.

PMID- 9186256
TI  - Ictal EEG and single photon emission computed tomography in a patient with
      cortical dysplasia presenting with atonic seizures.
AB  - PURPOSE: Ictal studies of atonic seizures in children with epilepsy are rare. To
      clarify the neurophysiologic mechanism of such seizures, we describe a cluster of
      atonic seizures in a 6-year-old girl with cortical dysplasia. METHODS: Ictal
      activity was recorded as slow-wave bursts beginning over the right frontocentral
      regions, where the cortical dysplasia was detected by magnetic resonance imaging
      (MRI), and propagating to the left hemisphere. RESULTS: The polygraphic recording
      demonstrated that the atonia indicated by the sudden interruption of
      electromyogram (EMG) discharges corresponded to the bilaterally synchronous spike
      and-wave complexes. An ictal single photon emission computed tomography (SPECT)
      study with 99mTc hexamethyl propylene amine oxime ([99mTc]HMPAO) simultaneously
      performed during EEG recording showed marked bilateral mesial frontal and right
      frontoparietal hyperperfusion. CONCLUSIONS: Our findings suggest that the
      neurophysiological mechanism of the atonic seizures may be produced by a strong
      inhibition in the bilateral motor cortexes. Ictal SPECT is valuable in
      demonstrating the pathophysiology of both atonic seizures and secondary
      bilaterally synchronous spike-and-wave complexes in the EEG.

PMID- 9186257
TI  - Recurrent seizures in the developing brain are harmful.

PMID- 9186258
TI  - Recurrent seizures in the developing brain are not harmful.

PMID- 9186259
TI  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

PMID- 9186260
TI  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

PMID- 9186262
TI  - Human leptin: the hormone of adipose tissue.

PMID- 9186263
TI  - Parathyroid hormone-related protein and its role in pregnancy, lactation, and
      neonatal growth and development.

PMID- 9186264
TI  - The adipocyte fatty acid-binding protein links obesity and insulin resistance.

PMID- 9186261
TI  - Growth hormone-releasing peptides.
AB  - Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides
      endowed with potent stimulatory effects on somatotrope secretion in animals and
      humans. They have no structural homology with GHRH and act via specific receptors
      present either at the pituitary or the hypothalamic level both in animals and in
      humans. The GHRP receptor has recently been cloned and, interestingly, it does
      not show sequence homology with other G-protein-coupled receptors known so far.
      This evidence strongly suggests the existence of a natural GHRP-like ligand
      which, however, has not yet been found. The mechanisms underlying the GHRP effect
      are still unclear. At present, several data favor the hypothesis that GHRPs could
      act by counteracting somatostatinergic activity both at the pituitary and the
      hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism.
      However, the possibility that GHRPs act via an unknown hypothalamic factor (U
      factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied
      in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides,
      GHRP-2 and Hexarelin, have been synthesized and are now available for human
      studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via
      GHRP receptors and their effects have been clearly demonstrated in animals and in
      humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting
      molecule. The GH-releasing activity of GHRPs is marked and dose-related after
      intravenous, subcutaneous, intranasal and even oral administration. The effect of
      GHRPs is reproducible and undergoes partial desensitization, more during
      continuous infusion, less during intermittent administration: in fact, prolonged
      administration of GHRPs increases IGF-1 levels both in animals and in humans. The
      GH-releasing effect of GHRPs does not depend on sex but undergoes age-related
      variations. It increases from birth to puberty, persists at a similar level in
      adulthood and decreases thereafter. By the sixth decade of life, the activity of
      GHRPs is reduced but it is still marked and higher than that of GHRH. The GH
      releasing activity of GHRPs is synergistic with that of GHRH, is not affected by
      opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory
      influences, including neurotransmitters, glucose, free fatty acids, gluco
      corticoids, recombinant human GH and even exogenous somatostatin, which are known
      to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in
      somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and
      hyperthyroidism. On the other hand, their good GH-releasing activity has been
      shown in some but not in other somatotrope hyposecretory states. In fact, reduced
      GH responses after GHRP administration have been reported in idiopathic GH
      deficiency as well as in idiopathic short stature, in obesity and in
      hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's
      syndrome the somatotrope responsiveness to GHRPs is almost absent. In short
      children an increase in height velocity has also been reported during chronic
      GHRP treatment. Thus, based on their marked GH-releasing effect even after oral
      administration, GHRPs offer their own clinical usefulness for treatment of some
      GH hyposecretory states.

PMID- 9186265
TI  - Transcription factors in the pathophysiology of diabetes mellitus.

PMID- 9186266
TI  - KATP channels and glucose-induced insulin release: lessons from persistent
      hyperinsulinemic hypoglycemia of infancy.

PMID- 9186267
TI  - Short- and long-term metabolic effects of recombinant human IGF-I treatment in
      patients with severe insulin resistance and diabetes mellitus.
AB  - In patients suffering from the genetic syndromes of severe insulin resistance it
      appears that diabetes develops when the adaptive hypersecretion of insulin fails
      and often these forms of diabetes will be insensitive to insulin treatment. The
      objective of the present study was to examine the metabolic and hormonal
      responses to an unchanged insulin therapy with the addition of a subcutaneous
      administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2
      weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg
      body weight) in four patients with extreme insulin-resistant diabetes mellitus
      and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a
      low dose (40 micrograms/kg body weight) in three of the four patients. Two
      siblings had known mutations in the tyrosine kinase domain of the insulin
      receptor and a deletion of exon 17 in part of their insulin receptor mRNA,
      whereas the remaining two patients were suspected to have defects at receptor
      and/or post-receptor sites. In the short-term study period, plasma glucose levels
      decreased more than 35% in response to rhIGF-I in all but one patient which was
      paralleled by reduced levels of serum insulin (25-50%), proinsulin (40-50%) and C
      peptide (10-65%) and an improvement in glycaemic control as evaluated by
      decreased glycosylated haemoglobin and serum fructosamine. During the long-term
      study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of
      treatment and fasting plasma glucose and serum insulin and C-peptide levels were
      decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor
      mutations. After 10 weeks of treatment fasting plasma glucose levels were still
      decreased whereas fasting serum insulin and C-peptide levels were increased
      almost to pretreatment values. IN CONCLUSION: 2 weeks of high-dose rhIGF-I
      therapy in insulin-treated patients with severe insulin resistance has a marked
      lowering effect on fasting plasma glucose and serum insulin levels whereas the
      metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I
      may be modest and transient.

PMID- 9186268
TI  - Oestrogen replacement does not restore the reduced GH-releasing activity of
      Hexarelin, a synthetic hexapeptide, in post-menopausal women.
AB  - Hexarelin (HEX), a synthetic hexapeptide, has a strong and reproducible GH
      releasing activity in man after intravenous, subcutaneous, intranasal and oral
      administration. Its effect undergoes age-related variations, being reduced in
      elderly subjects. In spite of evidence in animals showing that the activity of GH
      releasing peptides (GHRPs) is positively influenced by oestrogens, in young
      adults no sex-related difference has been found in the GH response to HEX or to
      other GHRPs. We aimed to clarify the influence of the menopause and oestrogens on
      the GH-releasing activity of HEX. We studied the GH response to the acute
      administration of the maximal effective dose of HEX (2 micrograms/kg i.v.) in 24
      young women (YW, age: 27.3 +/- 0.5 years: body mass index (BMI): 20.7 +/- 0.3
      kg/m2), 14 post-menopausal women (PW, age: 52.9 +/- 1.2 years: BMI: 23.2 +/- 0.9
      kg/m2) and 14 aged women (AW, age: 68.9 +/- 1.5 years: BMI: 21.7 +/- 0.7 kg/m2).
      In 10 post-menopausal women the GH response to HEX was also studied after 3
      months of transdermal oestradiol treatment (delivery 50 micrograms/die). Basal
      oestrogen and GH levels in PW were lower than those in YW (oestrogen: 4.8 +/- 3.6
      vs 42.0 +/- 3.4 pg/ml (means +/- S.E.M.). P < 0.001: GH: 1.5 +/- 0.5 vs 2.9 +/-
      0.6 micrograms/l, P < 0.02) and similar to those in AW (oestrogen: 1.3 +/- 0.4
      pg/ml: GH: 0.9 +/- 0.2 microgram/l). IGF-l levels in PW were not different from
      those in YW (174.4 +/- 11.9 vs 195.5 +/- 14.9 micrograms/l) and higher than those
      in AW (109.8 +/- 15.8 micrograms/l, P < 0.01). The GH response to HEX in PW
      (areas under the curve +/- S.E.M.: 453.6 +/- 56.0 micrograms.min/l) was lower (P
      < 0.002) than that in YW (1630.4 +/- 259.7 micrograms.min/l) while it did not
      differ from that in AW (781.8 +/- 189.3 micrograms.min/l). In PW 3-month
      oestrogen administration increased oestradiol levels (38.3 +/- 5.9 vs 0.8 +/- 0.4
      pg/ml, P < 0.001) making them similar to those recorded in YW, while it failed to
      modify both basal GH and IGF-l levels GH: 1.8 +/- 0.6 vs 1.5 +/- 0.7
      micrograms/l: IGF-l: 164.6 +/- 14.3 vs 175.0 +/- 12.3 micrograms/l). Also the GH
      response to HEX was not modified by oestradiol treatment (518.4 +/- 125.6 vs
      425.4 +/- 69.3 micrograms.min/l). In conclusion, present data confirm the strong
      GH-releasing effect of Hexarelin in humans and demonstrate that its activity is
      already reduced in post-menopausal women to an extent overlapping that in elderly
      women. Moreover, oestrogen treatment is not able to restore it. Thus, the lack of
      oestrogens does not seem to account for the reduced somatotraph responsiveness to
      GHRPs in the post-menopausal period.

PMID- 9186269
TI  - Serum FSH levels in women with polycystic ovary syndrome during ovulation
      induction using down-regulation and urofollitropin.
AB  - OBJECTIVE: To evaluate retrospectively the use of serum FSH levels and to
      correlate them with follicular growth in a clinical ovulation induction program.
      METHODS: Twenty women with infertility due to anovulation associated with
      polycystic ovary syndrome (PCOS) were studied. The patients were down-regulated
      with a long GnRH agonist protocol and stimulated with purified urofollitropin,
      using a low-dose step-up regimen. Repeated serum samples were drawn and
      transvaginal ultrasound scans were-performed. During the exogenous FSH therapy
      serum FSH levels resulting in continuous follicular growth were analyzed, as well
      as the rates of ovulation, pregnancy, cancellation and conversion to in vitro
      fertilization (JVF). RESULTS: Thirty-two out of fifty treatment cycles led to
      ovulation, resulting in five term pregnancies. Eight cycles were converted to
      IVF/embryo transfer due to multiple follicular growth. They resulted in two
      pregnancies. Ten cycles were cancelled because of impaired follicular growth. The
      serum FSH levels (median 6 IU/I) resulting in continuous growth of the follicles
      were relatively stable within patients (variation 15%) but varied considerably
      between patients (45%). The relationship between FSH dose and serum level was
      different for lean and obese PCOS patients after subcutaneously injected
      urofollitropin CONCLUSIONS: There seems to be a difference in
      resorption/metabolism between lean and obese PCOS patients with regard to s.c.
      injected FSH. The intra-patient coefficient of variation (C.V.) of the serum FSH
      response level was quite low, as was the C.V. of the FSH dose at the response
      level. This allowed a more rapid dose adjustment in subsequent cycles. Analysis
      of serum FSH during induction of ovulation with gonadotropins seems to be of
      limited value in clinical programs.

PMID- 9186270
TI  - Bioelectrical impedance assessment of body composition in thyroid disease.
AB  - To assess the metabolic effects of thyroid disease, body composition was
      determined by bioimpedance analysis (BIA) in 72 patients with untreated
      hyperthyroidism (mean age 48.7 +/- 1.9 years) and 26 patients with untreated
      hypothyroidism (63.8 +/- 3.4 years). Bioelectrical whole body resistance (R) and
      reactance (Xc) were used for computerized calculation of lean body mass (LBM),
      body cell mass (BCM), extracellular mass (ECM) and body fat (BF). Compared with
      age- and sex-matched healthy controls the most sensitive parameter indicating
      excess thyroid hormone was the ECM/BCM ratio which was markedly elevated in all
      hyperthyroid subjects. ECM/BCM alteration resulted from marked depletion of BCM
      with concomitant expansion of ECM. BCM change is thought to be predominantly due
      to a loss of muscle mass while ECM rise may reflect an increase in extracellular
      fluids. In contrast, hypothyroidism was characterized by an increase in BF
      besides a relatively unaffected LBM component. Serum parameters of thyroid
      function (tri-iodothyronine (T3), free thyroxine, TSH) did not correlate with the
      determinants of body composition except for a slight inverse relationship between
      the phase angle (Xc/Rx180 degrees/pi) and T3 concentration in Graves' disease
      patients. We conclude that hyperthyroidism is primarily accompanied by
      quantitative as well as qualitative changes in the lean body while considerable
      fat increase is the most important feature of hypothyroidism. Severity of body
      composition derangement cannot be predicted from the degree of thyroid
      dysfunction. BIA could become a useful tool which allows objective determination
      of even subtle metabolic manifestations of thyroid disease and should, therefore,
      complement conventional clinical and biochemical assessment.

PMID- 9186271
TI  - Assessment of thyroid growth stimulating activity of immunoglobulins from
      patients with autoimmune thyroid disease by cytokinesis arrest assay.
AB  - OBJECTIVE: To develop a novel bioassay for the assessment of thyroid cell growth
      stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs)
      from patients with autoimmune thyroid diseases. DESIGN: The assay is based on the
      principle that growing cells during incubation with CB show an increased number
      of nuclei in a cell (N/C index), since CB, at appropriate concentrations, is
      known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C
      index represents potential DNA production while cells are incubated with CB.
      METHODS: FRTL-5 thyroid cells were incubated with various thyroid stimulators in
      TSH-free medium containing 2 mg/J CB for 3 days. After the incubation, the cells
      were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped
      onto a glass slide, stained and observed under a microscope to determine the N/C
      index. RESULTS: Bovine TSH at 10(-3)-1.0 U/I, forskolin at 1x10(-7)-10(-5) mol/l,
      cholera toxin at 10x10(-5)-10(-3) mg/l, or (Bu)2cAMP at 1 x 10(-5)-10(-3) mol/l
      increased the N/C index up to approximately 2.0 in a dose-dependent manner. IgGs
      not only from 27 patients with untreated goitrous Graves' disease but also from
      14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C
      index, which exceeded the mean + 2 S.D. of the values for 17 normal subjects
      (mean +/- S.D., 1.063 +/- 0.014). Four patients with primary myxedema displayed a
      normal N/C index. In Graves' disease, the N/C index did not correlate
      significantly with thyroid stimulating antibodies (TSAb) activities but did
      correlate significantly with estimated goiter size (P < 0.05). IgGs containing
      blocking-type TSH-receptor antibodies inhibited the TSH- or Graves IgG-stimulated
      increase in N/C index almost completely, but did not influence the stimulatory
      effect of IgG from two patients with Hashimoto's thyroiditis. CONCLUSIONS: We
      have developed a sensitive and simple assay for thyroid growth stimulating
      activity by using CB, and found that all tested patients with goitrous Graves'
      disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating
      immunoglobulins whose activity does not correlate with TSAb.

PMID- 9186272
TI  - The revised 8307 base pair coding sequence of human thyroglobulin transiently
      expressed in eukaryotic cells.
AB  - We developed a transient transfection system for human thyroglobulin (TG) cDNA in
      both human thyroid cells and in COS-1 cells. Four overlapping TG cDNA fragments
      were amplified by reverse transcription-PCR from RNA of normal thyroid tissue.
      The most 5' fragment includes the natural translation initiation site and the
      sequence encoding the signal peptide (SP). After subcloning, the nucleotide
      sequence was determined and compared with the published human sequence, resulting
      in the detection of 30 nucleotide variations. For validation purposes, all
      variations were screened in 6-12 normal human alleles. Twenty-one were present in
      all screened alleles and have to be revised in the published nucleotide sequence.
      Since one variation concerns a triplet insertion, the coding sequence of the
      mature human thyroglobulin is 8307 nucleotides encoding 2750 amino acids. The TG
      cDNA constructs were transiently transfected in HTori 3 and COS-1 cells and
      protein expression was detected using a polyclonal anti-human-TG on fixed cells
      and after SDS-PAGE. In both cell-lines all four TG protein fragments were
      expressed. The mannose structures detected on the proteins by lectins and
      localization after expression in the cells suggest that only the N-terminal TG
      fragment (containing the SP) is directed to the endoplasmatic reticulum but is
      unable to reach the Golgi complex. The described expression system in human
      thyrocytes will be a helpful tool in studying the structure-function relationship
      of human TG in thyroid hormonogenesis.

PMID- 9186273
TI  - A novel approach to assess changes in endocrine secretion: analysis of GnRH
      antagonist (Nal-Glu) suppression of gonadotropin release in ovariectomized ewes.
AB  - Circulating hormone levels reflect the outcome of multiple feedback systems. A
      method to accurately assess the dynamics of hormonal changes in samples collected
      at infrequent intervals and compare these dynamic processes among treatment
      groups is presented. In this approach, a smooth curve is fitted to each time
      series of concentrations produced in an experiment, the curves are summarized by
      numerical measurements, and the measurements are subjected to statistical
      analysis. The method is demonstrated on data from an experiment that explores the
      differential effects of a competitive GnRH receptor antagonist (Nal-Glu) on
      circulating levels of LH and FSH. In this experiment, six adult ovariectomized
      Suffolk ewes were treated with one of three doses of Nal-Glu using a crossover
      design. LH and FSH concentrations were determined in hourly samples of jugular
      blood for 24 h after treatment. Applying the analytical approach, we observed
      differential effects of increasing concentrations of Nal-Glu on circulating LH
      and FSH concentrations. The magnitude of LH suppression was similar from dose to
      dose, while the duration of LH suppression was dose-dependent. In contrast, all
      doses of Nal-Glu elicited similar effects on the amplitude, duration and time to
      recovery of FSH suppression. Studies conducted in vitro utilizing dispersed ovine
      pituitary cells in culture demonstrated that the differential effects of Nal-Glu
      on FSH and LH secretion were not the outcome of differential sensitivity of FSH
      and LH to GnRH. The differential effects of Nal-Glu on circulating LH and FSH
      concentrations may be due to a number of factors, including other releasing or
      release-inhibiting hormones, paracrine modulators involved in selective
      regulation of FSH, and/or differences in clearances.

PMID- 9186274
TI  - Oxytocin-induced changes in single cell K+ currents and smooth muscle contraction
      of guinea-pig gastric antrum.
AB  - To study the effects of oxytocin on both spontaneous phasic contractions and K+
      outward currents (IK) of the so-called 'non-target' smooth muscle cells,
      physiological concentrations of oxytocin ranging between 10(-12) mol/l and 10(-8)
      mol/l were applied to smooth muscle preparations and single voltage-clamped cells
      isolated from the circular layer of the guinea-pig gastric antrum. Oxytocin (10(
      12) mol/l to 10(-8) mol/l) suppressed, in a dose-dependent manner, the
      tetrodotoxin- and atropine-resistant spontaneous phasic contractions and shifted
      rightward the dose-response curves of 10(-7) mol/l charybdotoxin and 10(-3) mol/l
      BaCl2. In cells with preloaded intracellular Ca2+ stores, oxytocin (10(-12) mol/l
      to 10(-9) mol/l) caused a dose-dependent activation of the charybdotoxin
      blockable non-inactivating component of IK (IK(sl)) of single voltage-clamped
      cells, which was accompanied by hyperpolarization of the cell membranes. 8Lys
      vasopressin and 8arg-vasopressin failed to mimic the effects of oxytocin on both
      contraction and K+ currents. Further, the oxytocin-induced activation of IK(sl)
      was effectively antagonized by 5 x 10(-8) mol/l U-73122 or 5 x 10(-6) mol/l 2
      nitro-4-carboxyphenyl N,N-diphenylcarbamate (inhibitors of the cell membrane
      phospholipase C), as well as by intracellularly applied heparin (selective
      inhibitor of inositol-1,4,5-trisphosphate (IP3)-induced Ca2+ release channels).
      In cells incubated in the absence of Ca2+ entry throughout the study, oxytocin
      (10(-9) mol/l) caused a slight and transient increase of IK(sl) amplitudes.
      Neither ryanodine (10(-6) mol/l) nor cyclopiazonic acid (10(-6) mol/l) were able
      to restore the IK-activating effect of oxytocin in these cells. The data obtained
      suggest (i) that selective oxytocin receptors are present on the membranes of
      guinea-pig antral smooth muscle cells, (ii) that the oxytocin-related relaxation
      may result from the activation of Ca(2+)-sensitive K+ conductivity via activation
      of IP3-induced release of Ca2+ from the submembrane located cisternae of the
      sarcoplasmic reticulum Ca2+ stores and (iii) in turn, this evokes a non
      inactivating component of IK, hyperpolarizing the cell membrane.

PMID- 9186275
TI  - Carbamoylcholine regulation of polyphosphoinositide synthesis and hydrolysis in
      cultured, dispersed, digitonin-permeabilized mouse pancreatic islet cells.
AB  - Continuing formation of inositol phosphates during stimulation of pancreatic beta
      cells by hormones and neurotransmitters requires the continued synthesis of the
      polyphosphoinositides phosphatidylinositol 4-phosphate (PIP) and
      phosphatidylinositol 4,5 bisphosphate (PIP2) from phosphatidylinositol (PI). In
      the present study we have investigated how this pathway and the activity of
      phosphoinositide-specific phospholipase C (PI-PLC) are regulated by
      carbamoylcholine (CCh), Ca2+, the phorbol ester 12-O-tetradecanoylphorbol 13
      acetate (TPA), GTP gamma S and NaF in 44-h [3H]inositol-labelled, dispersed and
      digitonin-permeabilized mouse pancreatic islet cells. CCh stimulated not only PI
      PLC (G-protein-mediated) but also, by an as yet unknown mechanism, significantly
      enhanced PI 4-kinase activity, estimated as the PIP:PI ratio, by 100%, and
      further increased the flux from PI to PIP and PIP2, GTP gamma S and NaF mimicked
      the effects of CCh on PI-PLC but had no effect on the levels of PIP and PIP2, TPA
      raised the PIP:PI ratio by 75%. In addition TPA counteracted the CCh stimulation
      of PI-PLC. There was no effect of 10(-6) mol/l Ca2+ on the levels of PIP and
      PIP2. Experiments with quinacrine and adenosine confirmed that PI-PLC and PI 4
      kinase could be regulated independently of each other. In conclusion, these data
      point to differential regulation of polyphosphoinositide synthesis and breakdown.

PMID- 9186276
TI  - Parathyroid hormone-related protein in neonatal and reproductive goats determined
      by a sensitive time-resolved immunofluorometric assay.
AB  - OBJECTIVE: High concentrations of parathyroid hormone-related protein (PTHrP)
      have been found in goat milk but it is not known whether it can enter the
      circulation of the neonate. In this study we have developed a sensitive two-site
      lanthanide immunofluorometric assay (IFMA) using dissociation and enhancement
      time-resolved fluorometry to address this question. METHOD: Affinity-purified
      anti-PTHrP 38-67 raised in rabbit was biotinylated and immobilized in
      streptavidin-coated microtitration wells as a 'capture' antibody. As a signal,
      affinity-purified anti-PTHrP 1-34, raised in sheep, was labeled with an europium
      chelate. A sensitivity of 0.3 pmol/l was achieved. PTHrP levels were determined
      in the plasma of eleven neonatal, seven parturient and six non-pregnant, non
      lactating goats as well as in goat milk. RESULTS: The circulating PTHrP levels
      (mean +/- S.D.) were significantly increased at day 1 (6.1 +/- 1.7 pmol/l: P <
      0.01) and day 3 (3.5 +/- 0.6 pmol/l: P < 0.05) after birth in the male kids (n =
      8) bottle-fed with milk from the dams, compared with before (2.2 +/- 0.7 pmol/l)
      and 30 min after (2.0 +/- 0.6 pmol/l) the first feeding and 14 days (2.4 +/- 0.8
      pmol/l) later. In the female kids (n = 3) fed with formula there was no such
      increase and the concentrations remained between 1.6-1.9 pmol/l. In the
      parturient goats the mean +/- S.D. PTHrP levels before, during and after
      parturition were 2.9 +/- 1.7, 4.2 +/- 2.4 and 3.7 +/- 2.2 pmol/l respectively (n
      = 7) which demonstrated that plasma PTHrP was higher during and after parturition
      in comparison with before (P < 0.05). The levels in non-pregnant, non-lactating
      goats were 3.3 +/- 1.5 pmol/l (n = 6). PTHrP levels in goat milk were in the
      nanomolar range and were highest in the colostrum. CONCLUSIONS: A significant
      increase of plasma PTHrP was observed in goat kids fed with milk from their dams
      and this increase was not found in kids fed with formula. Plasma PTHrP was also
      increased during parturition.

PMID- 9186277
TI  - An index predicting coronary heart disease: LDL/HDL x 5.
AB  - Atherosclerotic changes in the coronary artery are exacerbated by the balance
      between LDL, which carries cholesterol into the arterial wall, and HDL, which
      carries it out from the wall. The molecular weight of LDL is about 2 x 10(6) and
      that of HDL is about 4 x 10(5), which is almost 1/5 of the molecular weight of
      LDL. For this reason, LDL/HDL x 5 should be a good indicator of coronary heart
      disease. We evaluated this index in two subject groups. At first, we determined
      whether it could predict the incidence of effort angina in participants of a
      medical examination system. Most of the subjects were healthy and good candidates
      for primary prevention. LDL/HDL x 5 was a more sensitive index predicting effort
      angina than total cholesterol, LDL or HDL. The concentrations of HDL were
      significantly lower in myocardial infarction patients at all ages in both sexes.
      The average serum concentration of HDL was 56.6 +/- 15.0 mg/dl in the medical
      examination group and 38.9 +/- 12.2 mg/dl in the AMI group. We tested whether our
      new index, LDL/HDL x 5, could predict the incidence of re-infarction in patients
      with myocardial infarction who were candidates for secondary prevention. LDL/HDL
      x 5 was a more sensitive index predicting re-infarction than total cholesterol,
      LDL or HDL.

PMID- 9186278
TI  - A new approach to the development of anti-ischemic drugs. Substances that
      counteract the deleterious effect of lysophosphatidylcholine on the heart.
AB  - Lysophosphatidylcholine (LPC) is an amphiphilic metabolite that can be produced
      from membrane-phospholipids by activation of phospholipase A2 (PLA2), and it
      accumulates in the heart during ischemia and reperfusion. It is known that LPC is
      an arrhythmogenic substance. Recent studies have revealed that LPC produces
      mechanical and metabolic derangements in perfused working rat hearts, and Ca(2+)
      overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like
      effect on the heart. LPC accumulated in the myocardium activates phospholipase
      A2, establishing a vicious circle; i.e. LPC itself has an ability to produce
      another LPC. Therefore, a drug that has an anti-LPC effect would protect or
      improve ischemia/reperfusion damage. This article will review the effect of LPC
      in relation to ischemia, and consider a possibility of developing new anti
      ischemic drugs on the basis of the anti-LPC action.

PMID- 9186279
TI  - Influence of residual antegrade coronary blood flow on the long-term prognosis of
      medically treated patients with myocardial infarction and single-vessel disease.
AB  - We assessed the influence of residual antegrade coronary perfusion on long-term
      mortality and morbidity in 262 patients (256 men and 6 women, aged 52.3 +/- 9.8
      years) with medically treated old myocardial infarction and single-vessel disease
      who were followed for 117.0 +/- 39.8 months. Partial or complete antegrade
      coronary perfusion of the infarct artery was present in 165 patients (group I);
      no or minimal antegrade perfusion of the infarct artery was present in 97
      patients (group II). There was no significant difference in survival between
      group I (5-year survival rate, 96.9% and 10-year survival rate, 90.7%) and group
      II (93.8% and 92.7%, respectively). There was also no significant difference in
      the event free survival rate between group I (5-year, 92.6% and 10-year, 79.7%)
      and group II (89.5% and 74.8%, respectively). The extent of left ventricular
      dysfunction was an important determinant of prognosis: 10-year survival rates in
      patients with ejection fractions of > 60%, 40-60% and < 40% were 94.8%, 90.6% and
      74.8%, respectively. In the majority of patients the subsequent cardiac events
      were related to the progression of atherosclerosis in previously nonstenotic
      coronary arteries. Thus the presence or absence of residual antegrade coronary
      flow in the chronic phase of myocardial infarction did not significantly
      influence the long-term prognosis of patients with single-vessel disease.

PMID- 9186280
TI  - Effects of intracoronary adenosine triphosphate on coronary flow velocity
      dynamics in children.
AB  - To assess the usefulness of adenosine triphosphate (ATP) as an alternative agent
      for functional determination of coronary circulation in children and to reveal
      the dose-response kinetics of intracoronary ATP, systemic hemodynamics and
      spectral coronary flow velocity dynamics using Doppler guide wire were measured
      during hyperemic responses to an intracoronary bolus injection of ATP (0.01
      microgram/kg, 0.1 microgram/kg and 1.0 microgram/kg) in consecutive 40 Kawasaki
      disease patients (age: 8.4 +/- 5.1 years, 30 boys and 10 girls) without
      angiographic coronary lesions. ATP did not produce any significant change in
      heart rate, systolic blood pressure and mean blood pressure, but mildly decreased
      diastolic blood pressure. The coronary flow reserve (CFR) calculated as a ratio
      of hyperemic to basal averaged peak velocity (APV) for ATP was 2.05 +/- 0.31,
      2.26 +/- 0.38 and 2.50 +/- 0.51 in LAD, and 2.24 +/- 0.28, 2.44 +/- 0.41 and 2.60
      +/- 0.47 in RCA, respectively, for each of the three doses. There was no
      statistical significance between the mean values of CFR in LAD with ATP (1.0
      microgram/kg: 2.39 +/- 0.16) and papaverine (0.15 microgram/kg: 2.43 +/- 0.16) in
      six patients without angiographic coronary lesions. The maximal coronary
      hyperemia was reached rapidly after intracoronary bolus injection of ATP in all
      doses (10, 10-15 and 15-20 seconds in both LAD and RCA, respectively, for each of
      the three doses). The time required for APV to return to basal levels (< T10%)
      increased with the dose of ATP (30, 55 and 110 seconds in LAD and 35, 45 and 100
      seconds in RCA, respectively, for each of the three doses). Three patients (3/40:
      7.5%) developed transient (< 5 seconds) asymptomatic second degree
      atrioventricular block, but no patient had clinically significant arrhythmias.
      The change ratio in QTc interval after ATP injection was 1.96 +/- 1.87% (not
      significant). In addition, an intracoronary injection of ATP did not increase the
      absolute angiographic coronary luminal diameter. This study indicates that ATP is
      a safe alternative agent for pharmacological induction of coronary hyperemia for
      evaluation of coronary stenotic lesions and for the study of coronary circulation
      and coronary flow reserve in children.

PMID- 9186281
TI  - Dose-effect relationships of prostaglandin E1 in severe endstage chronic heart
      failure.
AB  - Prostaglandin E1 is a potent vasodilator in severe chronic heart failure. To
      evaluate the time sequence and magnitude of prostaglandin E1's hemodynamic
      effects a dose finding study was performed in 24 patients. Right heart
      catheterization was performed and prostaglandin E1 was administered via a central
      venous line in incremental doses of 2.5, 10, 20, 30 and 40 ng/kg/min, each dose,
      lasting 15 min before hemodynamic evaluation. The first significant change was a
      approximately 20% decrease in systemic vascular resistance index accompanied by a
      approximately 18% increase in cardiac index at an infusion rate of 2.5 ng/kg/min
      of prostaglandin E1, which was sustained at 5 ng/kg/min in all patients. A dose
      response-curve with cumulative doses ranging from 2.5 to 25 ng/kg/min of
      prostaglandin E1 was established in a subset of 14 patients due to 10 drop-outs
      at lower dosages. At 2.5 and 5 ng/kg/min of prostaglandin E1, cardiac index
      increased by 18% (p < 0.05) and peripheral resistance decreased by 18% (p <
      0.01). These changes were sustained up to a maximal dose of 25 ng/kg/min, which
      was tolerated by all patients in this group. At 15 and 20 ng/kg/min of
      prostaglandin E1 a significant decrease in blood pressure of -4 mmHg (p < 0.05)
      was observed which was reversed at the next dose step. In a second analysis
      maximal tolerated dosages of prostaglandin E1 were evaluated in all 24 patients
      (group A, 26 +/- 2 ng/kg/min), and in two subsets using a maximum tolerated dose
      of 20 ng/kg/min as a cutpoint (B: 14 patients, 34 +/- 2 ng/kg/min; C: 10
      patients, 15 +/- 2 ng/kg/min) Then the respective peak dosages were halved for
      continuous infusion through 12 hours. In the acute study pulmonary capillary
      wedge pressure (by A: -11%, p < 0.01; B: -4%, p < 0.01; C: -22%, p < 0.01) and
      systemic vascular resistance (by A: -32%, p < 0.0001; B: -25%, p < 0.001; C: 
      43%, p < 0.001) decreased significantly in all three groups and cardiac index
      increased (by A: +38%, p < 0.0001; B: +33%, p < 0.0001; C: +59%, p < 0.0001). In
      the chronic study these changes were sustained. Furthermore, mean arterial
      pressure (by A: -14%, p < 0.0001; B: -13%, p < 0.001; C: -13%, p < 0.05), right
      atrial pressure (by A: -36%, p < 0.0001; B: -36%, p < 0.01; C: -30%, p < 0.01),
      pulmonary artery pressure (by A: -16%, p < 0.0001; B: -16%, p < 0.01; C: -19%, p
      < 0.01) and pulmonary vascular resistance (by A: -28%, p < 0.01; B: -31%, p <
      0.01; C: -25%, p < 0.01) were significantly reduced after 12 hours. CONCLUSION:
      These results demonstrate potent hemodynamic effects of low-dose prostaglandin E1
      in severe heart failure. While systemic effects appear rapidly, a slow onset of
      the pulmonary effects was observed.

PMID- 9186282
TI  - Seasonal variations in the rupture of abdominal aortic aneurysms.
AB  - From 1982 to 1994, 54 patients (47 men; mean age 72 years) were referred to the
      Hospital of Ferrara, Italy for spontaneous rupture of abdominal aortic aneurysm.
      Sixteen died in the emergency department and 38 underwent urgent surgery. Day and
      month of onset of acute symptoms leading to urgent surgery were recorded. A
      seasonal variation with significant peaks in spring and autumn was found. These
      findings are likely influenced by local environmental, social and epidemiological
      factors, but may be relevant for the appropriate timing of the follow-up and
      therapeutic strategies for abdominal aortic aneurysms.

PMID- 9186283
TI  - Beneficial effects of testosterone undecanoate on the lipoprotein profiles in
      healthy elderly men. A placebo controlled study.
AB  - BACKGROUND AND METHODS: In order to assess the effects of testosterone
      undecanoate (TU; 120 mg/d orally for 2 months) on serum lipid, lipoprotein, and
      apolipoprotein levels in healthy elderly men, the placebo (PL) controlled study
      was performed on 37 elderly men, aged between 53 and 89 years. In all subjects
      venous blood samples were taken after an overnight (10 hours) fast and sera were
      stored -70 degrees C until analysis. RESULTS: In PL group, neither hormonal data
      nor lipid, lipoprotein, and apolipoprotein levels showed significant changes.
      After TU supplementation, serum total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), and estradiol (E2) levels decreased from 198 +/- 30.7 mg/dl
      to 174 +/- 41.9 mg/dl (p < 0.05), from 111 +/- 18.14 mg/dl to 87.9 +/- 29.4 mg/dl
      (p < 0.01), and from 86.2 +/- 16.9 pmol/l to 70.5 +/- 18 pmol/l (p < 0.01),
      respectively. Statistically significant differences were not observed in the
      serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and
      apolipoprotein (apo) A-1 and apo B levels after TU treatment. The mean ratios
      TC/HDL-C and LDL-C/HDL-C as coronary risk factor criteria decreased significantly
      in the TU but not in the PL group. No obvious side effect was observed in those
      who took TU except for reported pyrosis in 2 of 17 elderly men. CONCLUSIONS:
      These data indicate that the increased serum levels of total testosterone (TT)
      produced by administration of TU, 120 mg/d orally for 2 months lead to suppressed
      levels of TC and LDL-C and E2 but not significantly changed levels of TC, HDL-C,
      apo A-1 and apo B. Thus, we conclude that TU may be an effective drug for
      protecting coronary heart disease in healthy elderly men with lowered TT and FT
      levels. It may also have beneficial effects for sexual function and behavior.

PMID- 9186285
TI  - Continuous detection of superoxide in situ during ischemia and reperfusion in the
      rabbit heart.
AB  - In order to clarify the time course of superoxide generation in situ during
      ischemia and reperfusion in the rabbit heart, we used a method of enhanced
      chemiluminescence (CL) with 2-methyl-6-[p-methoxyphenyl]-3, 7-dihydroimidazo [1,
      2-alpha]pyrazin-3-one (MCLA) as a specific probe for detecting superoxide
      radicals. The surface of the rabbit heart was exposed to a photomultiplier tube
      in a light-proof box. We introduced a reversible snare occluder into the box to
      continuously observe the light emission. An ischemia-reperfusion group (I/R, n =
      7) was subjected to 30 mins of coronary occlusion, followed by 90 mins of
      reperfusion. We performed the same procedure (except for coronary occlusion) in
      the sham-operated group (n = 4). Another group of rabbits (n = 4) subjected to
      I/R received superoxide dismutase (SOD: 20 mg/kg, i.v.) during reperfusion to
      observe the CL response. In the I/R-group, the increase in CL began at 13 +/- 2
      (mean +/- SEM) mins and peaked at 52 +/- 12 mins of reperfusion. CL in the I/R
      group gradually increased from 818 +/- 350 counts/10 secs in the preischemic
      period to 1077 +/- 401 counts/10 secs during reperfusion (p < 0.01). In contrast,
      there was no increase in CL in the sham-operated group. The administration of SOD
      briefly attenuated CL by 24.1 +/- 6.8% for a period of 24.3 +/- 6.8 mins. The
      superoxide generation in situ in the ischemic rabbit heart appears to increase
      gradually and persists for a period following reperfusion.

PMID- 9186284
TI  - Increased lipoprotein (a) and its relationships with other parameters of
      lipoprotein metabolism in chronic renal failure treated by hemodialysis.
AB  - BACKGROUND: Studies have shown that patients with chronic renal failure have a
      high frequency of cardiovascular atheromatous disease. METHODS: We examined serum
      lipoprotein (a) [Lp(a)], very-low density lipoprotein cholesterol (VLDL-C), low
      density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol
      (HDL-C), apolipoprotein A1 (apo A1) and B (apo B), triglyceride (TG) and total
      cholesterol (TC) levels as possible risk factors for atherosclerosis in 45
      patients with chronic renal failure (CRF) treated by hemodialysis (HD) and in 15
      CRF patients who were not on HD. A control group of 20 healthy subjects was also
      studied. RESULTS: The proportion of smokers and body mass indexes were similar
      between the groups. In both patient groups, higher TG, TC and Lp(a) and lower apo
      A1 and HDL-C levels in serum were found than in those of controls. Serum apo B
      and LDL-C were similar in the patients treated by HD and the controls. Serum VLDL
      C and LDL-C were similar in the CRF patients who were not on HD and the controls.
      The highest ratios of apo B/apo A1 and LDL-C/HDL-C were found in HD patients. The
      highest ratio of TC/HDL-C was found in the other patient group. We found
      significant correlations between Lp(a) and other parameters of lipoprotein
      metabolism in CRF patients, both those who were and those who were not on HD.
      CONCLUSIONS: Our results indicate that CRF patients who both were and were not on
      HD show atherogenic changes in the lipoprotein pattern, and that the increase in
      Lp(a) during the CRF phase is basically related to the loss of renal function and
      may also depend on the resultant alterations which are produced in other
      lipoprotein variables.

PMID- 9186286
TI  - Catheter ablation of canine ventricular myocardium. The use of repetitive short
      time constant capacitive shocks to increase lesion volume.
AB  - Arching and barotrauma, seen with high energy DC catheter ablation, are
      responsible for diffuse cardiac damage and coronary sinus rupture. In six
      anesthetized dogs, we investigated the effects of an increasing number of short
      time-constant capacitive shocks on the volume of myocardial damage. Each dog
      received capacitive shocks of 2 J/kg at 3 sites in the left ventricle. One shock
      was delivered in 2 dogs, 2 shocks were delivered in 2 dogs and 3 shocks were
      delivered in 2 dogs. Shock delivery was not accompanied by hemodynamic collapse,
      sustained ventricular tachycardia or ventricular fibrillation. The dogs were
      sacrificed at 60 minutes. Mean (SEM) lesion volumes were 195 (39) mm3, 480 (41)
      mm3, and 595 (110) mm3, respectively. Despite variability in individual volume of
      damage, there was a significant increase in lesion volume with an increasing
      number of shocks. There was no evidence of perforation or tamponade. Increasing
      myocardial damage can be produced using repetitive capacitive shocks. Delivery of
      2 shocks produces clinically useful lesions without the adverse effects
      associated with single high energy shocks. Repetitive capacitive shocks offer a
      method of increasing lesion volume without increasing energy and thereby without
      compromising safety.

PMID- 9186288
TI  - Can isolated, symptomatic, frequent ventricular premature depolarizations be a
      predictor of an inducible ventricular tachycardia? Treatment by radiofrequency
      catheter ablation.
AB  - In this report, we describe a case of sustained ventricular tachycardia of right
      ventricular outflow tract origin, induced by dobutamine infusion in a patient
      with symptomatic, frequent ventricular premature depolarizations but no
      documented clinical ventricular tachycardia. Radiofrequency catheter ablation
      abolished not only the ventricular tachycardia itself, but also the frequent
      ventricular premature depolarizations responsible for all the symptomatology. In
      conclusion, provocation by catecholamine infusion may have a place in the search
      for an alternative to antiarrhythmic therapy in patients with isolated, frequent
      and symptomatic ventricular premature depolarizations.

PMID- 9186287
TI  - A case of acute myocardial infarction with reentrant sustained ventricular
      tachycardia developing in the prehospital phase.
AB  - A case of development of monomorphic sustained ventricular tachycardia in the
      prehospital phase of acute myocardial infarction is reported. By performing
      pacing from the right ventricular outflow tract during ventricular tachycardia,
      constant fusion and progressive fusion were documented without constant and
      progressive fusion from the right ventricular apex pacing, and it was terminated
      by pacing from the right ventricular outflow tract. Thus, reentry was considered
      to be the mechanism of this ventricular tachycardia occurring in the prehospital
      phase. Direct angioplasty successfully recanalized the totally occluded coronary
      artery, but late potential was present probably because of late reperfusion. In
      an electrophysiologic study in the chronic phase, slow conduction areas were
      found at the interventricular septum and the exit of this ventricular tachycardia
      was at the mid-septum of the right ventricle. A review of the literature failed
      to reveal any report of a similar case.

PMID- 9186289
TI  - Neonatal tuberous sclerosis with cardiac rhabdomyomas presenting as fetal
      supraventricular tachycardia.
AB  - A case of fetal tuberous sclerosis with multiple intracardiac rhabdomyomas
      exhibited persistent supraventricular tachycardia. The tachycardia was terminated
      by the use of cardiac version. The largest tumor almost occluded the right
      ventricular inlet portion. The obstruction was relieved after surgical removal of
      the largest tumor. No arrhythmia was noted after 3 months of follow-up.

PMID- 9186290
TI  - Concealed left ventricular hypertrophy and diastolic dysfunction in hypertrophic
      cardiomyopathy in the presence of acute left ventricular volume overload. A case
      report.
AB  - We report a patient in whom hypertrophic cardiomyopathy, with both left
      ventricular hypertrophy and diastolic dysfunction, was masked by acute severe
      aortic regurgitation and marked left ventricular dilation. Upon admission, 1) two
      dimensional echocardiogram of the left ventricle revealed a dynamic and flail
      vegetation on the aortic right coronary cusp and marked left ventricular
      dilation, 2) a massive aortic regurgitant signal was recorded by color Doppler
      flow imaging, and 3) transmitral flow velocity by pulsed Doppler echocardiogram
      revealed a pseudonormalization. However, symmetric hypertrophy of the left
      ventricular wall, a decrease in early diastolic wave and a compensatory increase
      in atrial systolic wave of the transmitral flow velocity appeared after
      successful aortic valve replacement.

PMID- 9186291
TI  - Recovery of iodine-123 metaiodobenzylguanidine uptake associated with left
      ventricular functional recovery in a patient with dilated cardiomyopathy.
      Endomyocardial histological findings before and after the improvement of uptake.
AB  - A 58-year-old man with idiopathic dilated cardiomyopathy was treated with
      incremental administration of a beta-blocker (metoprolol) and an angiotensin
      converting enzyme inhibitor (enarapril). The left ventricular end-diastolic
      dimension and ejection fraction improved in 8 months from 83.3 mm and 17.3% to 46
      mm and 69%, respectively. The washout ratio and heart-to-mediastinum ratio
      depicted on the delayed image for iodine-123 metaiodobenzylguanidine 123I-MIBG)
      uptake improved from 61.7% and 1.34 to 23.1% and 1.85, respectively, in
      association with improvement of left ventricular indices. Successive
      endomyocardial biopsy specimens disclosed reduction of the degrees of
      vacuolation, staining irregularity, and deformity of myocyte cytoplasm and
      nucleus compared to the findings before therapy. In this patient with dilated
      cardiomyopathy 123I-MIBG scintigraphy was useful for the evaluation of the
      effects of therapy. We conclude that it may be informative in the estimation of
      the histopathological abnormalities of the myocardium.

PMID- 9186292
TI  - Acute effects of progesterone on glucose metabolism in rat adipocytes: are they
      modulated by endogenous adenosine?
AB  - Progesterone rapidly inhibits glucose oxidation of isolated rat adipocytes.
      Because this inhibition is triggered by endogenous adenosine, the present study
      was designed to examine the effect of the steroid on cyclic adenosine
      monophosphate (cAMP) accumulation, its relation to lipolysis, and the possible
      participation of adenosine. The results strongly indicate that physiological
      concentrations of progesterone increase the release of adenosine by isolated
      adipocytes, with maximal release at the end of a 20-minute incubation.
      Progesterone decreased both cAMP levels and lipolysis in quiescent adipocytes or
      in adipocytes stimulated by isoproterenol. The increase of endogenous adenosine
      may explain the decline of cAMP and glycerol levels observed with progesterone.
      The effects of the steroid on lipolysis disappeared when adenosine was hydrolyzed
      by adenosine deaminase (ADA). On the other hand, in the absence of endogenous
      adenosine, the effect of progesterone on the cAMP level was decreased only in
      isoproterenol-stimulated cells. The inhibitory effects of progesterone on cAMP
      and glycerol production seem not to be related directly to the adenosine A1
      receptor, for selective A1 receptor antagonists (8-cyclopentyl-1,3
      dipropylxanthine [DPCPX] and CP 68,247) did not counteract these effects.
      However, mechanisms mediated by guanyl nucleotide binding proteins cannot be
      excluded. The decrease of cAMP and of lipolysis may be related to a stimulation
      of phosphodiesterases (PDEs). When PDEs I [Ca(2+)-calmodulin-regulated PDE
      family) were blocked by a selective inhibitor (CP 41,757), the progesterone
      inhibitory effect persisted, suggesting that PDEs I are not regulated by the
      steroid. On the other hand, the progesterone effect on cAMP accumulation but not
      on lipolysis disappeared in the presence of a selective inhibitor of the PDE IV
      family (cAMP-dependent-specific family). Ro 20.1724. When the specific inhibitor
      of PDE I or PDE IV was combined with ADA, the progesterone effect on cAMP
      disappeared. Taken together, these results suggest that the progesterone
      inhibitory action on cAMP levels was not mediated through A1 receptors or through
      activation of PDE I, but may be related to PDE IV activities. The progesterone
      effect on lipolysis seemed not to be directly related to changes in cAMP levels;
      an effect on PDE III activities in relation with the increase of adenosine
      release cannot be excluded.

PMID- 9186294
TI  - Amino acid handling in uremic rats: citrulline, a reliable marker of renal
      insufficiency and proximal tubular dysfunction.
AB  - The kidney is involved in amino acid reabsorption and metabolism; consequently,
      in renal insufficiency, these important functions are disturbed, as has been
      reported in animals and patients. In a first experimental series, rats were
      subjected to degrees of nephrectomy (NX) varying between 10% and 90%. Three weeks
      later, amino acid levels were measured in plasma to correlate the levels with the
      degree of NX. The results indicate that in the range of 33% to 74% NX, the plasma
      concentration of only three to four amino acids was modified, whereas in rats
      with 84% NX, the concentration of 11 amino acids was disturbed, compared with
      sham-operated rats. Citrullinemia was enhanced in uremic rats and correlated with
      the degree of NX. More interestingly, citrullinemia was increased in the range of
      10% to 33% NX without any changes in uremia and creatininemia, two well-known
      markers of uremic states. A second experimental series was designed to study the
      time course of changes in aminoacidemia to find a marker for the onset of renal
      failure. Rats were subjected to 36% NX for a period of 1 to 21 days. Uremia and
      creatininemia peaked 24 to 48 hours after NX, and creatinine clearance (Clcreat)
      concomitantly diminished. Unfortunately, these three markers of uremic states
      returned to control values during the next few days before increasing during the
      last 2 weeks. In contrast, citrullinemia increased twofold 48 hours after NX and
      plateaued over the next 20 days. We conclude that in rats, citrullinemia could be
      used (1) to detect acute and chronic renal failure, (2) as a specific marker of
      normal function of the proximal tubule, and (3) to estimate the degree of renal
      damage. From this study, renal insufficiency might be easily detected by
      measuring citrullinemia.

PMID- 9186293
TI  - Very-low-density lipoprotein subfraction composition and metabolism by adipose
      tissue.
AB  - Lipoprotein lipase (LPL) plays a pivotal role in very-low-density lipoprotein
      (VLDL) metabolism. Within the circulation, the VLDL population is heterogeneous
      with respect to both size and composition. Several studies have investigated the
      action of LPL in vitro on different VLDL subfractions, but little is known of the
      action of LPL in vivo. To investigate this, arterial and adipose tissue venous
      plasma samples were obtained from 16 normal male healthy volunteers (aged 24.4 +/
      1.8 years; body mass index, 23.5 +/- 0.7 kg.m-2) following an overnight fast.
      VLDL subfractions were isolated (VLDL1 of Sf 60 to 400 and VLDL2 of Sf 20 to 60)
      and characterized in terms of triacylglycarol (TAG) and apolipoprotein (apo) B,
      E, CI, CII, and CIII content. The apolipoprotein content of VLDL1 differed from
      that of VLDL2: the VLDL2 fraction contained significantly more apo B (0.018 +/-
      0.004 v 0.011 +/- 0.003 mumol.L-1, p = .001) but the ratios of TAG:apo B and apo
      CI:B, and CII:B, and CIII:B were significantly higher in VLDL1 (48,200 +/- 7,980
      v 13,860 +/- 2,420, 22.7 +/- 5.5 v 12.5 +/- 2.2, 45.0 +/- 6.3 v 14.9 +/- 2.0, and
      0.434 +/- 0.077 v 0.357 +/- 0.054, respectively, molar ratios, all P < .05). The
      venous blood draining an adipose tissue depot contained less VLDL1-TAG than
      arterial blood (328 +/- 68 v 381 +/- 83 mumol.L-1, respectively, P < .01),
      whereas VLDL2-TAG exhibited an opposite tendency (199 +/- 46 v 172 +/- 31 mumol.L
      1, NS). Concentrations of VLDL1-apo B, -apo CII, and -apo CIII were significantly
      less in adipose tissue venous blood compared with arterial blood (0.011 +/- 0.004
      v 0.013 +/- 0.004, 0.38 +/- 0.08 v 0.43 +/- 0.10, and 1.33 +/- 0.35 v 1.58 +/-
      0.38 mumol.L-1, respectively, all P < .05). These studies demonstrated novel
      differences in VLDL1 and VLDL2 in terms of composition and metabolism by human
      adipose tissue LPL in vivo.

PMID- 9186295
TI  - Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to
      experimental tuberculosis.
AB  - It has previously been shown that the n-3 polyunsaturated fatty acids (PUFAs)
      eicosapentaenoic acid (20:5(n-3)) and docosahexaenoic acid (22:6(n-3)) possess
      antiinflammatory properties and can interfere with immune functions. To evaluate
      whether this would affect resistance to infection, we studied the influence of
      different types of fatty acids (FAs) on experimental tuberculosis in an animal
      model. Three groups of 26 weanling guinea pigs were fed isocaloric diets with 26
      cal% fat that differed in FA composition with respect to saturated FAs, linoleic
      acid (18:2(n-6)), eicosapentaenoic acid (20:5(n-3)), and docosanexaenoic acid
      (22:6(n-3)) as follows: (1) reference (REF) group: 14.8 cal% saturated FAs and
      2.8 cal% linoleic acid; (2) n-6 group: 4.6 cal% saturated FAs and 15.4 cal%
      linoleic acid; (3) n-3 group: 6.3 cal% saturated FAs, 10 cal% linoleic acid, 1.4
      cal% eicosapentaenoic acid, and 0.9 cal% docosahexaenoic acid. After 13 weeks, 18
      animals from each group were intramuscularly injected with 180 colony-forming
      units (CFU) Mycobacterium tuberculosis strain H37Rv. Eight noninfected animals
      per group served as controls. Seven weeks later, the mean number of mycobacteria
      recovered from the spleens of the n-3 group (log 4.34 CFU, standard error of the
      mean [SEM], 0.12) was significantly higher than from the REF group (log 3.90 CFU;
      SEM, 0.15) and the n-8 group (log 3.93 CFU; SEM, 0.13; P < .05). In addition, the
      Root Index of Virulence (RIV) showed the most pronounced progression of the
      disease in the n-3 group. The mean size of the tuberculin reaction was larger in
      the n-3 group than in the other groups (P < .05). There was no significant
      difference between the n-6 group and the REF group. We conclude that
      supplementing the diet with n-3 FAs eicosapentaenoic acid and docosahexaenoic
      acid can affect resistance to M tuberculosis, whereas supplementing with n-6 FAs
      does not.

PMID- 9186296
TI  - Prospective 10-year evaluation of hypobetalipoproteinemia in a cohort of 772
      firefighters and cross-sectional evaluation of hypocholesterolemia in 1,479 men
      in the National Health and Nutrition Examination Survey I.
AB  - Our specific aim in a 10-year prospective study of 772 Cincinnati firemen
      (predominantly aged 26 to 46 years) was to determine the prevalence, attributes,
      and etiology of persistent hypobetalipoproteinemia, defined by entry low-density
      lipoprotein cholesterol (LDLC) less than 75 mg/dL. A second specific aim was to
      cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol
      [TC] < 130 mg/dL) in 1,314 white and 165 black men aged 26 to 46 years in the
      National Health and Nutrition Examination Survey (NHANES I). The 141 black and
      631 white firemen had 4,973 person-years of follow-up time (median, 7.1 yr/man).
      Of 772 men, 44 (5.7%) had entry LDL levels less than 75 mg/dL; they had a mean
      follow-up time of 7.3 yr/man. Of these 44 men, there were 12 (1.8% of the cohort)
      with entry LDLC less than 75 mg/dL, and at least 67% of their follow-up LDLC
      levels were less than 75. Their mean entry TC and LDLC levels were low (130 and
      58 mg/dL), mean triglyceride (TG) was low (63 mg/dL), and mean high-density
      lipoprotein cholesterol (HDLC) was high (60 mg/dL), LDLC remained at less than 75
      mg/dL in 81% of their follow-up samples. Their mean entry and follow-up
      cholesterol and LDLC did not differ (P > .1, 130 v 133 mg/dL and 58 v 63 mg/dL).
      Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of
      follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had
      lower mean Quetelet indices and diastolic blood pressure at entry (2.36 v 2.58, P
      = .056; 73 v 80 mm Hg, P = .03) and on follow-up study (2.45 v 2.69, P = .04; 72
      v 79 mm Hg, P = .05). Of 12 men with persistently low LDLC, two had truncated
      apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E
      genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated
      mortality from melanoma by 9 years and from alcoholism by 2 years. Comparable to
      white and black firemen aged 26 to 46 years, 2.9% and 3.6% of whom had entry
      serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I
      study (aged 26 to 46), 1.8% and 3.6% had hypocholesterolemia (entry TC < 130
      mg/dL). Daily mean calorie, fat, and protein intake (grams per day) did not
      differ (P > .05) in men with entry TC less than 130 mg/dL compared with those
      with TC 130 to 230 or greater than 230 mg/dL. Hypocholesterolemia in white and
      black men in NHANES I could not be attributed to hypocaloric intake or to
      protein, fat, or carbohydrate undernutrition. There appear to be racial
      differences in the prevalence of hypocholesterolemia. Blacks comprised 18% of the
      firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among
      NHANES I subjects, 3.6% of blacks were hypocholesterolemic versus 1.8% of whites.
      Unless persistent hypobetalipoproteinemia reflects an underlying disease,
      alcoholism, etc., it is often heritable, and may be associated with a reduced
      likelihood of coronary heart disease (CHD) and with increased longevity.

PMID- 9186297
TI  - Effect of tolrestat, an aldose reductase inhibitor, on neutrophil respiratory
      burst activity in diabetic patients.
AB  - One hypothesis for the reduction in oxidative killing of neutrophils in diabetic
      patients is that increased polyol pathway activity during hyperglycemia reduces
      intracellular levels of nicotinamide adenine dinucleotide phosphate (NADPH),
      resulting in the reduction of neutrophil superoxide production during the
      respiratory burst. To test this hypothesis, we assessed the effect of tolrestat,
      an aldose reductase inhibitor, on neutrophil respiratory burst activity (NRBA) in
      diabetic patients. We measured fasting plasma glucose (FPG), hemoglobin A1
      (HbA1), and NRBA levels in 79 diabetic patients and 48 normal controls. NRBA was
      reassessed in 34 patients after 4 weeks of tolrestat or placebo treatment, in
      seven controls after 4 weeks of tolrestat treatment, and in seven patients after
      4 weeks of blood glucose control. NRBA was determined by flow cytometry, which
      detected fluorescent 2',7'-dichlorofluorescein (DCF) in neutrophils formed from
      2',7'-dichlorofluorescein diacetate (DCF-DA) during phorbol myristate acetate
      (PMA)-induced respiratory bursts. Diabetic patients showed lower NRBA than the
      normal controls (mean cellular fluorescence, 438 +/- 103 v 668 +/- 101, mean +/-
      SD, P < .001). NRBA in diabetic patients showed a negative correlation with HbA1
      (r = -.336, P < .005). Tolrestat treatment for 4 weeks in 17 patients restored
      the reduced NRBA to an almost normal level (relative NRBA, 0.55 +/- 0.20 v 0.99
      +/- 0.36, P < .05) despite the fact that FPG level did not change (11.8 +/- 2.8 v
      11.4 +/- 2.8 mmol/L). NRBA of these patients after tolrestat treatment was not
      significantly different from that of seven control subjects treated with
      tolrestat for 4 weeks. In 17 placebo-treated patients, there were no significant
      changes in NRBA and FPG level. The vigorous blood glucose control for 4 weeks in
      seven patients (16.6 +/- 2.1 v 8.6 +/- 2.3 mmol/L) also restored the reduced NRBA
      to almost normal (relative NRBA, 0.55 +/- 0.21 v 0.90 +/- 0.30, P < .05). The
      result that the reduced NRBA in diabetic patients was restored to almost normal
      either by tolrestat treatment or by blood glucose control strongly supports the
      hypothesis of this study.

PMID- 9186298
TI  - Pancreatic alpha-cell function in idiopathic reactive hypoglycemia.
AB  - Idiopathic reactive hypoglycemia (IRH) is a well-documented but overdiagnosed
      syndrome. The presence of transient hypoglycemia and enhanced insulin secretion
      and/or increased insulin sensitivity before the onset of IRH is well documented.
      However, the data regarding glucagon secretion are sparse. Therefore, this study
      assessed glucagon and insulin responses to (1) oral ingestion of 100 g glucose
      oral glucose tolerance test (OGTT) and (2) a 100-g protein meal after an
      overnight fast in a randomized sequence at intervals of 7 to 10 days in five
      subjects with previously well-documented IRH and six normal subjects. Basal
      plasma glucose and insulin levels were not significantly different in both
      groups. However, basal glucagon was significantly higher (P < .025) in IRH
      subjects (347 +/- 83 ng/L) compared with normals (135 +/- 20 ng/L). In IRH
      subjects during the OGTT, hypoglycemia (2.7 +/- 0.11 mmol/L) occurred at 150 +/-
      16 minutes and was preceded by a markedly higher (P < .01) peak glucose
      concentration (11.7 +/- 0.6 mmol/L) at 36 +/- 6 minutes in comparison to normals
      (8.8 +/- 0.4 mmol/L), indicating the presence of impaired glucose tolerance in
      these subjects. Similarly, the plasma insulin increase was significantly higher
      (P < .01) but delayed in IRH subjects compared with normals. In contrast,
      glucagon suppression was not significantly different in both groups, although
      glucagon failed to increase following hypoglycemia in IRH. During a protein meal,
      plasma glucose declined in both groups, with a significantly (P < .05) greater
      decrease in IRH subjects (-0.8 +/- 0.2 mmol/L) compared with normals (0.5 +/- 0.1
      mmol/L). However, the glucagon increase was significantly (P < .01) blunted in
      IRH subjects (61% +/- 15%) in comparison to normals (152% +/- 39%). Thus, basal
      hyperglucagonemia with normal glucose concentration may suggest the presence of a
      hyposensitivity of the glucagon receptor in IRH. Moreover, the lack of
      appropriate suppression during the OGTT despite marked hyperglycemia, the lack of
      an increase at the onset of hypoglycemia, and the inhibited response to a protein
      meal in IRH subjects compared with normals denote altered glucagon secretion in
      IRH. Therefore, it is likely that glucagon receptor downregulation and impaired
      glucagon sensitivity and secretion may contribute to postprandial hypoglycemia in
      IRH.

PMID- 9186299
TI  - Cryopreservation: in vitro results in rat pancreatic islets.
AB  - Cryopreservation is an effective method of islet storage and may facilitate
      clinical trials of islet transplantation. It was the aim of the present study to
      evaluate the in vitro viability of cryopreserved rat islets, including the
      response to nonglucose secretagogues and glucose oxidation. After pancreatic
      digestion via intraductal injection of collagenase, 75- to 200-micron Wistar rat
      islets were handpicked and cultured in RPMI 1640 (glucose 11.1 mmol/L) and
      randomized into two groups: control (cultured 20 to 24 hours at 37 degrees C) and
      cryopreserved (after 20 to 24 hours of culture at 37 degrees C, islets were
      cryopreserved according to Rajotte's protocol: freezing velocity, -0.25 degree
      C/min; thawing velocity, 200 degrees C/min). In the two groups, we evaluated
      recovery, insulin content per islet, staining viability (ethidium bromide/orange
      acridine; semiquantitative scoring, measuring the viable area of the islet from 0
      = less viable to 3 = more viable), insulin secretion after glucose and nonglucose
      secretagogues, and oxidation of D-[U-14C]glucose. The results for the control
      group were always higher for the following: recovery (95.4% +/- 1.2% v 83.0% +/-
      2.1%, P = .00), insulin content (2,203.9 +/- 335.2 v 1,443.3 +/- 171.8
      microU/islet, P = .03), insulin secretion after 5.5 mmol/L glucose (61.3 +/- 8.0
      v 28.3 +/- 3.4 microU/islet/90 min, p = .00), 16.7 mmol/L glucose (151.4 +/- 16.1
      v 98.7 +/- 14.1 microU/islet/90 min, p = .03), 10 mmol/L L-leucine +10 mmol/L L
      glutamine (125.6 +/- 27.9 v 56.8 +/- 6.4 microU/islet/90 min, P = .05), and 10
      mmol/L L-arginine (202.5 +/- 27.5 v 128.8 +/- 14.2 microU/islet/90 min, P = .01),
      and glucose oxidation at 5.5 mmol/L (12.5 +/- 1.1 v 7.9 +/- 0.6 pmol/islet/120
      min, P = .00) and at 16.7 mmol/L (26.1 +/- 2.6 v 14.3 +/- 1.6 pmol/islet/120 min,
      P = .00). No significant differences in staining viability were found between
      groups (2.35 and 2.48, respectively, P = .55). However, cryopreserved and control
      islets showed a significant increase in insulin secretion and glucose oxidation
      after increasing the glucose concentration from 5.5 to 16.7 mmol/L. We conclude
      that when glucose is increased, cryopreserved islets keep the capacity to
      increase insulin secretion, but cryopreservation produces a significant decrease
      in several islet viability characteristics. This decrease may be due to a decline
      of beta-cell number per islet and/or a decrease in the content of insulin per
      beta cell.

PMID- 9186300
TI  - Lipoprotein lipase-enhanced binding of lipoprotein(a) [Lp(a)] to heparan sulfate
      is improved by apolipoprotein E (apoE) saturation: secretion-capture process of
      apoE is a possible route for the catabolism of Lp(a).
AB  - Recently, it has been recognized that cell-bound heparan sulfate (HS)
      proteoglycans (HSPG) are able to bind and subsequently initiate degradation of
      lipoproteins. Two mediators of lipoprotein catabolism, both with HS binding
      capacity, lipoprotein lipase (LPL) and apolipoprotein E (apoE), are involved in
      this process. This mechanism is known as the secretion-capture process of apoE.
      Lipoprotein(a) [Lp(a)] was shown to have a strong binding capacity to cell
      associated HSPG. This binding capacity was increased by LPL addition. We
      investigated the effects of recombinant apoE (r-apoE) enrichment of Lp(a) on the
      binding to HS. Lp(a), isolated by ultracentrifugation and gel filtration, was
      incubated with r-apoE and reisolated by ultracentrifugation, resulting in r-apoE
      enriched Lp(a). ApoE-enriched Lp(a) and control Lp(a) were coated to microtiter
      plates. The capacity to bind biotin-conjugated HS (b-HS) in the presence or
      absence of inactivated bovine LPL was studied. R-apoE-enriched Lp(a) showed
      increased b-HS binding capacity versus control Lp(a). Addition of LPL resulted in
      an increased b-HS binding capacity of both control and r-apoE-enriched Lp(a). To
      investigate whether binding of Lp(a) to endothelial cell HSPG occurred in vivo,
      39 volunteers were injected with heparin (50 U/kg) and plasma lipid and Lp(a)
      levels were determined before and 20 minutes after heparin injection. No
      significant increase in plasma Lp(a) concentrations was found. The results showed
      that Lp(a) can be enriched with apoE and that this resulted in increased LPL
      enhanced binding to HSPG. From the in vitro studies, it can be concluded that the
      secretion-capture process of apoE is a possible catabolic route for Lp(a).
      However, whether this also occurs in vivo remains to be confirmed.

PMID- 9186301
TI  - Retinoid-X receptors and the effects of 9-cis-retinoic acid on insulin secretion
      from RINm5F cells.
AB  - Retinoid-X receptors (RXRs) are 9-cis-retinoic acid (9CRA)-dependent gene
      transcription factors, which modulate the action of all-trans-retinoic acid
      (ATRA), fatty acids, thyroid hormone (TH), and vitamin D (VD) by forming dimers
      with themselves or ATRA, TH, peroxisome proliferator activator receptors (PPARs),
      or VD receptors (VDRs). To determine if 9CRA and RXRs have a role in secretion,
      RINm5F cells were assayed for RXR transcripts and effects of 9CRA and ATRA on
      secretion. A single RXR alpha transcript and two RXR beta transcripts, but not
      RXR gamma, were evident by Northern blot. Cells were cultured for 48 hours
      without and with 9CRA 1 to 1,000 nmol/L and then stimulated with glucose 0, 0.5,
      2.8, 7, and 11 mmol/L 9CRA increased secretion at each glucose concentration,
      9CRA increased secretion by 50% to 100% (ANOVA, P < .001) with consistent
      concentration-dependent responses (eg. at glucose 2.8 mmol/L 9CRA: 0 nmol/L, 5.02
      +/- .20 ng/(10(6) cells.h); 1 nmol/L, 6.97 +/- .30; 10 nmol/L, 8.36 +/- .18; 100
      nmol/L, 9.15 +/- .28; 1,000 nmol/L, 10.24 +/- .24; n = 6). Although RINm5F cells
      respond slightly if at all to glucose, 9CRA facilitated glucose-induced insulin
      release (eg, at 9CRA 100 nmol/L, glucose: 0.5 mmol/L, 7.47 +/- .22 ng/(10(6)
      cells.h); 2.8 mmol/L, 9.15 +/- .27; 7 mmol/L, 9.81 +/- .19; 11 mmol/L, 11.16 +/-
      .23; n = 6). ATRA increased secretion by 28% to 57% (ANOVA, P < .001: at glucose
      2.8 mmol/L, ATRA: 0 nmol/L, 6.17 +/- .32 ng/(10(6) cells.h); 1 nmol/L, 7.91 +/-
      .29; 10 nmol/L, 9.75 +/- .14; 100 nmol/L, 9.66 +/- .33; n = 6). 9CRA was more
      potent than ATRA (eg, at 2.8 mmol/L; baseline, 8.17 +/- .32 ng/(10(8) cells.h);
      ATRA 100 nmol/L, 9.66 +/- .33; 9CRA 100 nmol/L, 10.81 +/- .15; P < .05, n = 6).
      When 9CRA was combined with ATRA, the combination was not additive or synergistic
      (eg, at 2.8 mmol/L: ATRA 100 nmol/L, 9.66 +/- .33 ng/(10(6) cells.h); 9CRA 100
      nmol/L, 10.81 +/- .15; ATRA 100 nmol/L + 9CRA 100 nmol/L, 10.79 +/- .28; P < .05,
      n = 6). These studies show that (1) 9CRA stimulates insulin secretion from RINm5F
      cells. This effect appears to be at least equal to if not greater than that
      observed with ATRA, but additive or synergistic effects with ATRA were not
      evident; (2) 9CRA may facilitate glucose-induced release; and (3) multiple RXR
      transcripts are present in insulin-secreting cells, implying specific functions.
      Our findings support the idea that the effects of 9CRA on insulin secretion are
      mediated through RXR homodimers or heterodimers with retinoic acid receptors
      (RARs) or possibly other nuclear receptors. Retinoid deficiency or alterations in
      retinoid receptor function could lead to abnormalities of cell growth or
      secretion.

PMID- 9186302
TI  - Advanced glycation end products in serum predict changes in the kidney morphology
      of patients with insulin-dependent diabetes mellitus.
AB  - The biochemical mechanisms that cause the development and progression of diabetic
      nephropathy are unknown. Advanced glycation end products (AGEs) might play a
      role, as shown by increased levels of tissue-bound and circulating AGEs that
      correlate with the severity of diabetic nephropathy. The aim of the present study
      was to investigate if circulating AGEs predict the progression of morphological
      pathology in patients with diabetic nephropathy. We have developed an immunoassay
      to determine serum levels of AGEs. In a prospective clinical trial of young
      insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria, kidney
      biopsies were taken at baseline and after 24 to 36 months. The biopsies were
      analyzed for structural changes in the glomeruli by quantitative morphometry
      (electron microscopy). We have retrospectively analyzed serum AGEs. The mean
      serum level of AGEs at the start of the study was 18.7 U/mL (95% confidence
      interval [CI], 16.9 to 20.5). A positive correlation between serum AGE levels at
      the start of study and changes from baseline to follow-up study in basement
      membrane thickness (r = .56, P < .02) and matrix/glomerular volume fraction (r =
      .57, P < .02) was demonstrated. In a stepwise regression analysis with changes in
      the matrix/glomerular volume fraction as the dependent variable, serum AGE levels
      at the start of the study proved to be a significant independent variable (P <
      .02), whereas the mean hemoglobin A1c (HbA1c) or HbA1c at the start was not. This
      study shows that serum AGEs predict the progression of early morphological kidney
      damage during 2.5 years in patients with IDDM.

PMID- 9186303
TI  - Effects of dietary fat modification on fibrinogen, factor VII, and plasminogen
      activator inhibitor-1 activity in subjects with impaired glucose tolerance.
AB  - Our aim was to assess the impact of a monounsaturated fat-enriched (Mono) diet
      and a diet recommended by the National Cholesterol Education Program (NCEP) on
      plasma levels of fibrinogen and activities of factor VII (FVII:C) and plasminogen
      activator inhibitor-1 (PAI-1) and the impact of genetic polymorphisms of these
      variables (HaeIII, MspI, and 4G/5G polymorphisms, respectively) in 28 subjects
      with impaired glucose tolerance ([IGT] 17 men and 11 women; mean age, 55.6 +/-
      5.5 years). A diet rich in fat and saturated fatty acids served as a baseline
      diet for 3 weeks. Thereafter, subjects were randomized for the next 8 weeks to
      either the Mono diet (n = 12) or NCEP diet (n = 18). Fibrinogen levels or PAI-1
      activities did not change with either of the diets, but fibrinogen levels were
      higher (3.4 +/- 0.5 v 4.0 +/- 0.6 g/L, P = .007 at baseline) throughout the study
      in heterozygous subjects with respect to HaeIII polymorphism. This polymorphism
      and age accounted for 38% of the variation of fibrinogen levels. MspI
      polymorphism together with body mass index explained 51% of the variation of
      FVII:C, which was higher in subjects with the M1M1 genotype compared with
      M1M2/M2M2 genotypes (127% +/- 21% v 90% +/- 12%, P < .001). FVII:C showed a
      decrease with the NCEP diet (P < .05), but the decline was confined to M1M1
      subjects. PAI-1 activity did not differ significantly between the genotypes. The
      insulin sensitivity index (SI) obtained by the minimal model method was the main
      explanatory variable of PAI-1 activity. To conclude, despite good compliance, the
      fat-modified diet did not alter plasma levels of fibrinogen or PAI-1 in white
      subjects with IGT. FVII:C levels decreased with the NCEP diet, but this was
      confined to subjects with the M1M1 genotype.

PMID- 9186304
TI  - Insulin attenuates atrophy of unweighted soleus muscle by amplified inhibition of
      protein degradation.
AB  - Unweighting atrophy of immature soleus muscle occurs rapidly over the first
      several days, followed by slower atrophy coinciding with increased sensitivity to
      insulin of in vitro protein metabolism. This study determined whether this
      increased sensitivity might account for the diminution of atrophy after 3 days of
      tall-cast hindlimb suspension. The physiological significance of the increased
      response to insulin in unweighted muscle was evaluated by analyzing in vivo
      protein metabolism for day 3 (48 to 72 hours) and day 4 (72 to 96 hours) of
      unweighting in diabetic animals either injected with insulin or not treated.
      Soleus from nontreated diabetic animals showed a similar loss of protein during
      day 3 (-16.2%) and day 4 (-14.5%) of unweighting, whereas muscle from insulin
      treated animals showed rapid atrophy (-14.5%) during day 3 only, declining to
      just -3.1% the next day. Since fractional protein synthesis was similar for both
      day 3 (8.6%/d) and day 4 (7.0%/d) of unweighting in insulin-treated animals, the
      reduction in protein loss must be accounted for by a slowing of protein
      degradation due to circulating insulin. Intramuscular (IM) injection of insulin
      (600 nmol/L) stimulated in situ protein synthesis similarly in 4-day unweighted
      (+56%) and weight-bearing (+90%) soleus, even though unweighted muscle showed a
      greater in situ response of 2-deoxy-[3H]glucose uptake to IM injection of either
      insulin (133 nmol/L) or insulin-like growth factor-I (IGF-I) (200 nmol/L) than
      control muscle. These findings suggest that unweighted muscle is selectively more
      responsive in vivo to insulin, and that the slower atrophy after 3 days of
      unweighting was due to an increased effect of insulin on inhibiting protein
      degradation.

PMID- 9186305
TI  - How (not) to diagnose growth hormone deficiency in adults: stimulated serum
      concentrations of growth hormone in healthy subjects and in patients with
      pituitary macroadenomas.
AB  - The secretion of growth hormone (GH) stimulated by GH-releasing hormone ([GHRH]
      100 micrograms intravenously [IV]) was determined in 33 patients with
      nonfunctioning pituitary macroadenomas before and after transsphenoidal
      adenomectomy and in 28 controls. Patients who needed substitution therapy for at
      least one additional pituitary hormone presented with lower GH secretion than the
      remaining patients with pituitary tumors. However, there was a marked overlap of
      stimulated GH secretion between these two groups (3.2 +/- 4.3 ng/mL and 7.2 +/-
      6.6 ng/mL, respectively) and between either group with the control group (7.1 +/-
      5.5 ng/mL). In an independent investigation, the effect of IV GHRH (100
      micrograms) on the secretion of GH in seven healthy volunteers was shown to be
      comparable to that seen during an insulin tolerance test ([ITT] 0.1 U/kg IV).
      Thus, the GHRH stimulation test, a simple and comparatively unharmful procedure,
      is a useful alternative to the ITT in patients with potential pituitary defects.
      However, the pronounced overlap of stimulated serum GH concentrations in patients
      with pituitary macroadenomas and those estimated in healthy subjects and in
      patients with nonpituitary diseases underlines the difficulty in biochemically
      defining acquired GH deficiency in adults. We suggest that GH therapy in adults
      should primarily be instituted in patients with additional defects in anterior
      pituitary function.

PMID- 9186306
TI  - Lactate infusion in anesthetized rats produces insulin resistance in heart and
      skeletal muscles.
AB  - Plasma lactate is elevated in many physiological and pathological conditions,
      such as physical exercise, obesity, and diabetes, in which a reduction of insulin
      sensitivity is also present. Furthermore, an increased production of lactate from
      muscle and adipose tissue together with increased gluconeogenic substrate flux to
      the liver plays a primary role in enhancing hepatic glucose production (HGP) in
      diabetes. It has been shown that lactate may interfere with the utilization and
      oxidation of other substrates such as free fatty acids (FFAs). The aim of this
      study was to investigate if lactate infusion affects peripheral glucose
      utilization in rats. Animals were acutely infused with lactate to achieve a final
      lactate concentration of 4 mmol/L. They were then submitted to a euglycemic
      hyperinsulinemic clamp to study HGP and overall glucose metabolism (rate of
      disappearance [Rd]). At the end of the clamp, a bolus of 2-deoxy-[1-3H]-glucose
      was injected to study insulin-dependent glucose uptake in different tissues. The
      results show that lactate infusion did not affect HGP either in the basal state
      or at the end of clamp, whereas glucose utilization significantly decreased in
      lactate-infused rats (26.6 +/- 1.1 v 19.5 +/- 1.4 mg.kg-1.min-1, P < .01). A
      reduction in the tissue glucose utilization index was noted in heart (18.01 +/-
      4.44 v 46.21 +/- 6.51 ng.mg-1.min-1, P < .01), diaphragm (5.56 +/- 0.74 v 9.01 +/
      0.93 ng.mg-1.min-1, P < .01), soleus (13.62 +/- 2.29 v 34.05 +/- 6.08 ng.mg
      1.min-1, P < .01), and red quadricep (4.43 +/- 0.73 v 5.88 +/- 0.32 ng.mg-1.min
      1, P < .05) muscle in lactate-infused animals, whereas no alterations were
      observed in other muscles or in adipose tissue. Therefore, we suggest that acute
      lactate infusion induces insulin resistance in the heart and some muscles, thus
      supporting a role for lactate in the regulation of peripheral glucose metabolism.

PMID- 9186308
TI  - Dietary soy protein and estrogen replacement therapy improve cardiovascular risk
      factors and decrease aortic cholesteryl ester content in ovariectomized
      cynomolgus monkeys.
AB  - Estrogen replacement therapy (ERT) decreases the progression of coronary artery
      atherosclerosis in monkeys. Dietary soy protein also retards the progression of
      atherosclerosis relative to animal proteins such as casein. Soy protein contains
      weakly estrogenic compounds called isoflavones or phytoestrogens that may be
      responsible for the cardioprotective effects. This study was designed as a 2 x 2
      factorial to determine the magnitude of soy protein's effects on cardiovascular
      risk factors relative to casein and lactalbumin, with or without estradiol
      treatment. Ovariectomized female monkeys were randomized to four treatment groups
      based on past dietary cholesterol consumption, their origin, and past
      reproductive history, and studied for 7 months. The animals were divided into (1)
      a group fed casein and lactalbumin as the protein source (n = 14), (2) a group
      fed casein and lactalbumin as the protein source plus 17 beta-estradiol (E2) (n =
      13), (3) a group fed soybean protein isolate as the protein source (n = 11), and
      (4) a group fed soybean protein isolate as the protein source plus E2 (n = 10).
      Soy protein compared with casein consumption resulted in a significant
      improvement in plasma lipid and lipoprotein concentrations, a significant
      improvement in insulin sensitivity and glucose effectiveness as determined by
      minimal-model analyses, and a decrease in arterial lipid peroxidation. E2-treated
      monkeys had a significant reduction in fasting insulin levels and insulin to
      glucose ratios, total body weight, and amounts of abdominal fat, and had smaller
      low-density lipoprotein (LDL) particles. In addition, E2 treatment resulted in a
      significant reduction (P = .001) in aortic cholesteryl ester content. A similar
      trend (P = .14) was found for soy protein compared with casein. There also was a
      significant interaction (P = .02) with soy and E2, such that animals consuming
      soy protein +E2 had the least arterial cholesteryl ester content. These results
      suggest that both ERT and dietary soybean protein have beneficial effects on
      cardiovascular risk factors. Interestingly, the two treatments affected different
      risk factors and together resulted in the greatest reduction in arterial
      cholesterol content. Further studies are needed to determine the active component
      of the soy protein and to assess its long-term effects on the cardiovascular
      system and other organ systems (such as the bones and reproductive system).

PMID- 9186307
TI  - Tissue-specific effects of chronic dietary protein restriction and gastrostomy on
      the insulin-like growth factor-I pathway in the liver and colon of adult rats.
AB  - Dietary protein restriction decreases plasma concentrations of insulin-like
      growth factor-I (IGF-I) and reduces IGF-I mRNA levels in the liver. In addition
      to the actions of systemic IGF-I, locally produced IGF-I is thought to mediate
      autocrine and paracrine growth effects in the colon. The objectives of the
      present study were to investigate the IGF-I pathway in the colon and liver of
      adult rats under conditions of dietary protein restriction, surgical stress, and
      dietary protein repletion. Two groups of rats were placed on either a 20% or 2%
      casein diet for 19 days. Two additional groups of rats underwent gastrostomy
      after a 2% casein diet for 2 weeks, and then were either kept on the 2% casein
      diet or changed to a 20% casein diet until day 19. Dietary protein restriction
      reduced plasma concentrations of IGF-I and IGF-binding proteins (IGFBPs) and
      hepatic IGF-I mRNA content, while increasing colonic IGF-I receptor mRNA.
      Gastrostomy in protein-depleted animals had no effect on hepatic IGF-I mRNA, but
      led to a marked increase in colonic IGF-I mRNA levels. Dietary protein repletion
      resulted in a decrease in colonic IGF-I receptor mRNA. The distinct effects of
      dietary protein depletion and operative stress on the IGF pathway in the colon as
      compared with the liver may serve to maintain the level of IGF-I signaling in the
      colon by autocrine or paracrine mechanisms under these conditions.

PMID- 9186309
TI  - Growth hormone (GH) response to GH-releasing peptide-6 in patients with insulin
      dependent diabetes mellitus.
AB  - In insulin-dependent diabetes mellitus (IDDM), inappropriate growth hormone (GH)
      responses to several stimuli, including GH-releasing hormone (GHRH), have been
      described. A decreased hypothalamic somatostatinergic tone is one of the most
      likely explanations for these findings. His-DTrp-Ala-Trp-DPhe-Lys-NH2 [GH
      releasing peptide-6 [GHRP-6]] is a synthetic hexapeptide that stimulates GH
      release in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but
      it probably does not inhibit hypothalamic somatostatin secretion. Also, GHRH and
      GHRP-6 apparently activate different intracellular pathways to release GH. The
      aim of this study was to evaluate whether there is a differential effect of IDDM
      on GHRP-6- and GHRH-induced GH secretion. Six patients with IDDM and seven
      control subjects were studied. Each subject received GHRP-6 (1 microgram/kg
      intravenously [IV]), GHRH (100 micrograms IV), and GHRP-6 + GHRH on 3 separate
      days. GH peak values (mean +/- SE in micrograms per liter) were similar in
      controls and diabetics after GHRH (22.5 +/- 7.8 v 24.0 +/- 9.7) and after GHRP-5
      (20.5 +/- 5.3 v 24.4 +/- 6.3). The association of GHRP-6 and GHRH induced a
      significantly higher GH release than administration of the isolated peptides in
      both groups. The synergistic GH response to combined administration of GHRP-6 and
      GHRH was not different in controls (70.5 +/- 20.0) and diabetics (119.0 +/-
      22.2). In summary, the effectiveness of GHRP-6 in IDDM could reinforce the
      evidence that this peptide probably does not release GH through a decrease in
      hypothalamic somatostatin secretion. Moreover, our data suggest that both GHRH
      and GHRP-6 releasing mechanisms are unaltered in IDDM.

PMID- 9186310
TI  - Effect of smoking cessation on lipoprotein A-I and lipoprotein A-I:A-II levels.
AB  - Cigarette smoking is associated with low plasma high-density lipoprotein
      cholesterol (HDL-C) and apolipoprotein (apo) A-I levels, which may explain, in
      part, its deleterious effects on coronary heart disease (CHD). In a group of ex
      smokers, we assessed the influence of smoking cessation on apo A-I particle
      levels. Plasma lipid, apolipoprotein, and lipoparticle concentrations of 58
      subjects who had completely stopped smoking (ex-smokers) were compared with those
      of 37 subjects who had continued smoking (smokers) before and after a smoking
      cessation counseling program. Nutritional intake was recorded before and after
      the program to adjust for potential interaction with plasma lipid variables.
      Smokers and ex-smokers were similar in gender distribution, age, body mass index
      (BMI), social status, and nutrient intake. There were significantly greater
      increases in total cholesterol (P < .04), HDL-C (P < .005), HDL2-C (P < .008),
      and lipoprotein (Lp) A-I:A-II (P < .04) in ex-smokers than in smokers. After
      smoking cessation, ex-smokers consumed more vegetable protein (P < .02) and
      polysaccharides (P < .04) and had higher plasma levels of HDL-C (P < .0004), apo
      A-I (P < .001), Lp A-I (P < .007), and Lp A-I:A-II (P < .01) than smokers.
      Adjustments on nutritional variables did not show any additional difference
      between ex-smokers and smokers, suggesting that smoking per se effects Lp A-I and
      Lp A-I:A-II levels. In conclusion, HDL particles including Lp A-I and Lp A-I:A-II
      are higher in ex-smokers than in smokers.

PMID- 9186311
TI  - Acute effect of troglitazone on glucose metabolism in the absence or presence of
      insulin in perfused rat hindlimb.
AB  - Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma
      glucose by enhancing insulin action in insulin-resistant diabetic animals and non
      insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct
      effect of troglitazone on glucose metabolism and insulin action in skeletal
      muscle, we infused troglitazone solution into perfused rat hindlimbs in the
      presence of 6 mmol/L glucose and in the absence or presence of insulin. In the
      absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake.
      Troglitazone did increase lactate and pyruvate release at concentrations of 20
      mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P
      ratio) and increased oxygen consumption at concentrations higher than 5 and 20
      mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased
      glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in
      the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal
      effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in
      lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30
      minutes together with 250 microU/mL insulin, insulin-induced glucose uptake
      significantly increased 30 minutes after troglitazone infusion, and this increase
      was further augmented after withdrawal of troglitazone. In insulin plus
      troglitazone infusion at 30 minutes after troglitazone removal, glycogen content
      in hindlimb muscle was significantly decreased compared with that obtained with
      insulin infusion alone. In summary, in the absence of insulin, troglitazone does
      not elicit glucose uptake, but causes an increase in glycolysis accompanied by a
      decrease in muscle glycogen content and L/P ratio and an increase in oxygen
      consumption. In the presence of insulin, troglitazone increases insulin-induced
      glucose uptake, and this increase is further augmented after troglitazone
      removal. Addition of troglitazone to insulin infusion decreased the glycogen
      content in hindlimb muscle. This decrease in muscle glycogen content may trigger
      an enhancement of insulin-induced glucose uptake similar to that observed during
      muscle contraction or epinephrine treatment.

PMID- 9186312
TI  - This month in investigative urology. Apoptosis and benign prostatic hypertrophy.

PMID- 9186313
TI  - Use of extracorporeal shock waves in the treatment of pseudarthrosis,
      tendinopathy and other orthopedic diseases.
AB  - PURPOSE: The use of shock waves in orthopedic diseases was reviewed with special
      regard to the clinical applications. MATERIALS AND METHODS: Findings in the
      literature and results from our own studies were analyzed and summarized.
      RESULTS: Extracorporeal shock waves induced osteoneogenesis in animal models with
      intact and fractured bones. Based on these findings shock waves were used for the
      treatment of pseudarthrosis in humans. Most patients had at least 1 unsuccessful
      operation before shock wave therapy. Complete reunion was noted in 62 to 91% of
      cases and shock waves are recommended by some as the first choice of treatment
      for hypertrophic pseudarthrosis. After failed nonoperative therapy shock waves
      were used for the treatment of patients with various diseases as secondary
      treatment. The success rate for treatment of tendinopathies, such as tennis
      elbow, periarthritis humeroscapularis or calcaneal spur, was approximately 80%.
      For calcific tendinitis shock wave therapy seems to be superior to all other
      minimal or noninvasive techniques without compromising a potential later
      operation. CONCLUSIONS: Shock waves have changed medical therapy substantially.
      Accounting for the epidemiology of the treated diseases, this new change may
      equal or even surpass the impact of extracorporeal shock wave lithotripsy.

PMID- 9186314
TI  - The relationship between prostatic intraepithelial neoplasia and prostate cancer:
      critical issues.
AB  - PURPOSE: Prostatic intraepithelial neoplasia (PIN) is often considered to be a
      premalignant lesion and the main precursor of invasive carcinoma of the prostate.
      We evaluated the evidence for and against PIN as a premalignant lesion and
      determined guidelines for the clinical management of PIN. MATERIALS AND METHODS:
      Literature analysis of histopathological, morphometric, phenotypic and molecular
      genetic evidence of progression and of clinical findings regarding PIN was done.
      Literature searches were performed on MEDLINE with relevant key words. RESULTS:
      PIN, like prostate cancer, occurs most frequently in the peripheral zone of the
      prostate and is usually located in close proximity to prostate cancer. The
      relative PIN and prostate cancer volumes vary inversely. Prostate specific
      antigen in cases of PIN appears to be intermediate between prostate cancer and
      normal levels, although this elevation may be explained by concomitant prostate
      cancer or benign prostatic hyperplasia. Deoxyribonucleic acid ploidy in PIN
      follows the aneuploid proportion as in the concomitant prostate cancer. Prostate
      cancer and PIN show evidence of loss of putative tumor suppressor genes on
      chromosome 8p. The clinical relevance of PIN biopsy findings is based on the
      association of neoplasia and prostate cancer. High grade PIN in core biopsies
      without concomitant prostate cancer has a substantial risk for prostate cancer in
      subsequent biopsies (24 to 73%, up to 100% when the digital rectal examination is
      suspicious) and should cause further biopsy sampling. CONCLUSIONS: There is
      convincing evidence that PIN is a precursor lesion to prostate cancer, with a
      close association of PIN and prostate cancer in biopsy and prostatectomy
      specimens. A biopsy finding of high grade PIN necessitates further investigation
      in patients who are candidates for radical treatment for localized prostate
      cancer.

PMID- 9186315
TI  - Long-term results of retropubic permanent 125iodine implantation of the prostate
      for clinically localized prostatic cancer.
AB  - PURPOSE: The historical series of retropubic prostate radioactive source
      implantation from the Memorial Sloan-Kettering Cancer Center has served as the
      framework for the current transperineal implant approaches used in the treatment
      of localized prostatic cancer. We report the final assessment of the 15-year
      outcome. MATERIALS AND METHODS: Between March 1970 and December 1987, 1,078
      patients with biopsy proved adenocarcinoma of the prostate were treated at our
      cancer center with permanent implantation of 125iodine via a retropubic approach.
      In addition, all patients underwent bilateral pelvic lymphadenectomy before
      implantation. The clinical stages of disease were B1 in 234 patients (22%), B2 in
      472 (44%), B3 in 145 (14%) and C in 227 (20%). Of the patients 733 (68%) had
      pathologically negative lymph nodes, whereas 345 (32%) had positive lymph nodes
      at lymph node dissection. Median followup was 11 years. RESULTS: Multivariate
      analysis identified nodal involvement, high grade disease, clinical stage B3/C
      and implant doses less than 140 Gy, as independent predictors of local relapse.
      Independent predictors of distant metastases included nodal involvement, stage
      B3/C disease and poorly differentiated histological status. The local recurrence
      free survival rates for patients with negative nodes at 5, 10 and 15 years were
      69, 44 and 24%, respectively. The distant metastases-free survival rates at 5, 10
      and 15 years for patients with negative lymph nodes were 59, 36 and 21%,
      respectively. CONCLUSIONS: 125Iodine implantation of the prostate via the
      retropubic approach was associated with a greater than expected incidence of
      local relapse at 15 years. Technical limitations of the retropubic technique
      resulting in suboptimal distribution of the isotope within the prostate are
      believed to be the explanation for the inferior local control outcome. Although
      long-term results are not yet available, the 5-year results of the computer
      optimized transperineal prostate implantation suggest that improved implant
      techniques will translate into a greater likelihood of tumor control.

PMID- 9186316
TI  - Protease inhibitors and urolithiasis.
AB  - PURPOSE: We discuss the specific urological abnormalities associated with
      protease inhibitor therapy. MATERIALS AND METHODS: We report on a human
      immunodeficiency virus positive patient who was on protease inhibitor therapy and
      presented with renal colic. RESULTS: The stone passed spontaneously. Stone
      analysis was not consistent with any known composition of urinary calculus.
      CONCLUSIONS: The positive effects of protease inhibitors in human
      immunodeficiency virus positive patients mandate that the urological community
      become familiar with these drugs and the specific urological complications as the
      use of these drugs becomes widespread.

PMID- 9186317
TI  - The effects of (L)-2-oxothiazolidine-4-carboxylate on urinary oxalate excretion.
AB  - PURPOSE: A phase I study was done to evaluate the safety and pharmacokinetics of
      (L)-2-oxothiazolidine-4-carboxylate (OTZ). An ancillary objective was to compare
      the effects of treatment with 2 levels of OTZ to placebo on urinary oxalate
      excretion in healthy male subjects. MATERIALS AND METHODS: Individuals underwent
      intravenous infusion of 70 (6) or 100 (6) mg/kg, body weight OTZ, or placebo for
      2 hours at 4, 8-hour intervals. Urine was collected during the 12 hours before
      treatment, and at 0 to 4, 4 to 8, 8 to 24, 24 to 28, 28 to 32 and 32 to 48 hours
      after the initial infusion. Urine samples were assayed for creatinine, oxalate,
      citrate, sulfate, urate, phosphate and pH. RESULTS: Urinary oxalate excretion
      relative to creatinine decreased significantly in the 100 mg./kg. dose group by
      4.1 mg./gm. during the first 24 hours and by 4.6 mg./gm. in 24 to 48 hours
      compared to baseline values (p < 0.05). Slight decreases of 0.9 and 1.1 mg./gm.,
      respectively, in the 70 mg./kg. dose group, and 1.6 and 2.3 mg./gm.,
      respectively, in the placebo group were observed. Oxalate excretion on day 2 in
      the 100 mg./kg. dose group was significantly less than that in the placebo group
      (p = 0.04). Urinary pH decreased and sulfate excretion increased with OTZ
      therapy. CONCLUSIONS: Treatment with 100 mg./kg. OTZ every 8 hours decreases
      urinary oxalate excretion in healthy men.

PMID- 9186318
TI  - Long-term survival after surgical revascularization for atherosclerotic renal
      artery disease.
AB  - PURPOSE: We analyzed the long-term clinical outcome and survival after surgical
      revascularization for atherosclerotic renal artery stenosis. MATERIALS AND
      METHODS: The study group comprised 222 patients who underwent surgical
      revascularization for atherosclerotic renal artery stenosis between 1974 and
      1987. The indications for performing surgical revascularization were treatment of
      hypertension in 60 patients, preservation of renal function in 12, and control of
      hypertension and preservation of renal function in 148. Postoperative blood
      pressure, renal function and survival data were analyzed during a mean followup
      of 7.4 years. RESULTS: There were 5 operative deaths (2.2%) and postoperative
      thrombosis or stenosis of the repaired renal artery occurred in 16 patients
      (7.3%). Long-term cure or improvement of renovascular hypertension was achieved
      in 72.4% of patients. Preoperative renal function correlated significantly with a
      favorable blood pressure response to surgical revascularization (p = 0.013). Long
      term improvement or stabilization of renal function was achieved in 71.3% of
      patients. Preoperative renal function (p = 0.034) and bilateral atherosclerotic
      renal artery stenosis (p = 0.04) correlated significantly with a favorable renal
      function result after surgical revascularization. Actuarial 5 and 10-year
      survivals for the entire series from the time of surgical revascularization were
      81 and 53%, respectively. The expected 5 and 10-year survivals for a comparable
      healthy population are 89 and 77%, respectively. Using a multivariate analysis,
      factors correlating with diminished long-term survival were age older than 60
      years (p = 0.002), coronary artery disease (p = 0.031), and previous vascular
      operations (p = 0.001). CONCLUSIONS: These data support the long-term therapeutic
      efficacy of surgical revascularization in patients with atherosclerotic renal
      artery stenosis. The merits of newer forms of therapy, such as percutaneous
      transluminal angioplasty and endovascular stenting, must ultimately be weighed
      against these results.

PMID- 9186319
TI  - Renal cell carcinoma of native kidneys: prospective study of 129 renal transplant
      patients.
AB  - PURPOSE: We evaluated the prevalence of renal cell carcinoma of the native
      kidneys in renal transplant recipients as well as possible risk factors.
      MATERIALS AND METHODS: A total of 129 consecutive renal transplant recipients
      underwent ultrasound examination of the native kidneys as part of a routine
      evaluation. A record was made of acquired cystic kidney disease, defined as 3
      cysts or more, and of suspicious masses. When a malignancy was suspected radical
      nephrectomy was performed. RESULTS: The overall prevalence of renal cell
      carcinoma of the native kidney was 5 in 129 recipients (3.9%). All cancers were
      limited to the kidney. No significant relationship was detected between renal
      cell carcinoma occurrence and patient age, dialysis (when initiated, type and
      duration), transplantation, drug regimen or incidence of acquired cystic kidney
      disease. CONCLUSIONS: The risk of renal cell carcinoma, a clinically significant
      cancer, was approximately 100 times greater in our renal transplant patients than
      in the general population but no significant risk factor could be identified.
      Routine ultrasonography for early diagnosis in asymptomatic patients on
      immunosuppressive therapy is strongly recommended to improve prognosis.

PMID- 9186320
TI  - Microscopic vascular invasion is the most relevant prognosticator after radical
      nephrectomy for clinically nonmetastatic renal cell carcinoma.
AB  - PURPOSE: Although many factors have been considered to predict the outcome after
      radical nephrectomy, renal cell carcinoma continues to behave unpredictably. In a
      retrospective study the correlation between microvascular tumor invasion and
      disease-free survival after surgery for renal cell carcinoma was analyzed.
      MATERIALS AND METHODS: Between 1980 and 1993, 180 patients (mean age 60 years)
      were followed for a mean of 52 months after radical or partial nephrectomy for
      clinically localized renal cell carcinoma. The relevance of microscopic vascular
      invasion was compared to classical tumor staging, grade and tumor diameter.
      RESULTS: Microscopic vascular invasion was found in 51 patients (28.3%),
      including 20 (39.2%) with progression (mean interval to progression 72 months).
      Of 129 patients with no pathological evidence of microscopic vascular invasion
      only 8 (6.2%) showed progression at a mean interval of more than 160 months. The
      difference in disease-free survival as a function of microvascular invasion was
      statistically highly significant (log rank p < 0.00001) and on multivariate
      analysis this parameter was by far the most relevant predictor of progression.
      CONCLUSIONS: In patients who underwent radical nephrectomy for clinically
      nonmetastatic renal cell carcinoma with microvascular invasion but without lymph
      node involvement or macroscopic vascular invasion the chance of disease
      progression is estimated at 45% within 1 year. Microvascular invasion is the
      single most relevant prognosticator after presumed curative radical nephrectomy
      for renal cell carcinoma.

PMID- 9186321
TI  - The use of metallic stents to bypass ureteral strictures secondary to metastatic
      prostate cancer: experience with 8 patients.
AB  - PURPOSE: We evaluated the middle term patency, incidence of infection and ability
      to preserve renal function using metallic stents to bypass ureteral obstruction
      secondary to metastatic prostate adenocarcinoma. MATERIALS AND METHODS: We
      studied 8 patients with ureteral obstruction secondary to metastatic prostate
      adenocarcinoma at the pelvic ureter with up to 48 months of followup. Metallic
      Wallstents* 8 mm. in diameter and 64 mm. long were placed across the stricture
      after preliminary dilation with a high pressure balloon. Double-J catheters were
      left in all patients for at least 1 month or until mucosal edema had subsided.
      All stents were placed via an antegrade approach. RESULTS: Average duration of
      stent patency was 19 months. All 6 patients at risk at 12 months had patent
      stents compared to 3 of 5 at 24 months, 2 of 2 at 36 months, and 1 of 1 at 48
      months. Stent occlusion occurred in 2 patients at 8 and 12 months, respectively,
      and additional stents were placed telescopically to achieve recanalization. Renal
      function was preserved in all patients. Two patients died of disease at 1 month
      and 1 at 26 months after stent placement. CONCLUSIONS: The use of metallic stents
      to bypass malignant ureteral obstruction is a safe and effective method.

PMID- 9186322
TI  - Metal stents: a new treatment of malignant ureteral obstruction.
AB  - PURPOSE: We report our experience with the use of metallic self-expandable and
      balloon expandable stents for the treatment of malignant ureteral obstruction.
      MATERIALS AND METHODS: We treated 12 consecutive patients with malignant ureteral
      obstruction, for a total of 14 ureters with stents placed. We placed metallic
      balloon expandable stents in 6 patients and self-expandable metallic stents in
      the remaining 6. Mean patient age was 65 years and mean followup was 9 months
      (range 8 to 16). RESULTS: Of the ureters 11 were patent without any additional
      manipulations during followup of 8 to 16 months. Secondary interventions were
      needed in 3 cases because of obstructive urothelial hyperplastic reaction, tumor
      ingrowth and local recurrence of the primary cancer invading the upper end of the
      stent. Two patients died 2 and 10 months after placement of the stent.
      CONCLUSIONS: Both types of metal stents have advantages and disadvantages that
      must be balanced against each other when choosing the ideal device for the
      treatment of obstruction. Implantation of a metal self-expanding or balloon
      expanding stent is safe and effective for the palliative treatment of malignant
      ureteral obstruction in late stage cancer patients.

PMID- 9186323
TI  - Accuracy of residual urine measurement in men: comparison between real-time
      ultrasonography and catheterization.
AB  - PURPOSE: The practical value of ultrasonography as a rapid means to determine
      accurately residual urine volume was assessed. MATERIALS AND METHODS: Transverse
      and sagittal bladder diameters, as well as areas from longitudinal and transverse
      images, were measured with real-time ultrasonography in 324 men immediately after
      voiding. Calculated bladder volumes using measured diameters and areas for each
      of 11 formulas in the literature were compared to the corresponding measured
      total residual urine volumes. RESULTS: The lower limit of ultrasonographic
      visualization of urine in the bladder was approximately 48 ml. No correlation
      existed between ultrasound calculated bladder volumes and measured residual urine
      for any of the 11 formulas. CONCLUSIONS: Ultrasonography cannot rapidly measure
      bladder volumes accurately to date. Catheterization remains the most accurate
      method of assessing post-void residuals but in many cases it may not be the best
      approach to patient care.

PMID- 9186324
TI  - The treated natural history of high risk superficial bladder cancer: 15-year
      outcome.
AB  - PURPOSE: The long-term outcome of patients with high risk superficial bladder
      cancer is unknown. We report the results of 15 years of followup of high risk
      patients treated initially with aggressive local therapy, including transurethral
      resection alone or combined with intravesical bacillus Calmette-Guerin. MATERIALS
      AND METHODS: Between 1978 and 1981, 86 high risk patients enrolled in a
      randomized study of transurethral resection alone or with intravesical bacillus
      Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse
      carcinoma in situ and 44% had stage T1 tumors before entry into the study.
      Patients were followed until death (61%) or until the present time (median
      followup 184 months). RESULTS: Disease stage progressed in 46 patients (53%) and
      31 (36%) eventually underwent cystectomy for progression (28) or refractory
      carcinoma in situ (3), while 18 (21%) had upper tract tumors at a median of 7.3
      years. The 10 and 15-year disease specific survival rates were 70 and 63%,
      respectively. At 15 years 34% of patients overall were dead of bladder cancer,
      27% were dead of other causes and 37% were alive, including 27% with an intact
      functioning bladder. CONCLUSIONS: Despite aggressive local therapy patients with
      high risk superficial bladder cancer are at lifelong risk for development of
      stage progression and upper tract tumors. A third of patients are at risk for
      death from bladder cancer, justifying careful and vigilant long-term followup.
      These results support the use of initial aggressive local therapy in patients
      with high risk superficial bladder cancer.

PMID- 9186325
TI  - Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages
      pTa and pT1): a randomized prospective study.
AB  - PURPOSE: We performed a prospective, randomized, controlled study to compare
      intravesical epirubicin and doxorubicin as adjuvant therapy after endoscopic
      resection of superficial bladder tumor. MATERIALS AND METHODS: We randomly
      allocated 253 eligible patients to 4 study arms. Seven to 14 days after
      transurethral bladder tumor resection instillation of the intravesical agent was
      instituted, including 50 and 80 mg. epirubicin in study arms 1 and 2,
      respectively, and 50 mg. doxorubicin in arm 3. Control arm 4 included patients
      who underwent transurethral bladder tumor resection alone. Instillation was
      repeated weekly for 8 weeks and monthly thereafter to complete 1 year of
      treatment. All patients were followed every 3 months by cystourethroscopy, urine
      cytology and deoxyribonucleic acid flow cytometry for 12 to 48 months (mean
      30.1). RESULTS: Rates of recurrence were significantly lower in the chemotherapy
      groups than in controls (p < 0.001) and in the epirubicin groups than in the
      doxorubicin group (p = 0.02). In arms 1 to 4 recurrence rates were 25, 17.6, 36.7
      and 65.6%, respectively. Recurrence rates per 100 patient months were 0.83, 0.60,
      1.18 and 2.73, respectively, which were significant statistically, and lower
      after chemotherapy in general and epirubicin in particular (p < 0.05). Mean
      interval to first recurrence was 16, 15.4, 18.9 and 6.3 months, respectively,
      with a significant difference between the chemotherapy and control groups (p <
      0.05). Progression to muscle invasive disease occurred in 7 (10.9%), 3 (4.4%), 6
      (10%) and 5 patients (8.2%), respectively, in arms 1 to 4 (p > 0.05). We studied
      the relationships among different risk factors, and patterns of recurrence and
      progression. For pT1 tumors recurrence rates in arms 1 to 4 were 26.3, 17.8, 39.3
      and 70.9%, respectively, which were significantly lower in the chemotherapy group
      than in controls (p < 0.001) and in the epirubicin groups than in the doxorubicin
      group (p = 0.01). Toxic and untoward side effects developed in 10 (15.6%), 16
      (23.5%) and 25 (41.7%) patients in chemotherapy arms 1 to 3, respectively, with a
      marginal insignificant difference between low and high dose epirubicin (p = 0.3),
      and significantly lower toxicity rates in arms 1 and 2 than in 3 (p = 0.002). A
      contracted bladder developed in 2.1% of all patients who received chemotherapy.
      CONCLUSIONS: This study demonstrates that epirubicin has better efficacy and
      lower toxicity than doxorubicin when used as an intravesical agent.

PMID- 9186326
TI  - Immunohistochemical description of nitric oxide synthase isoforms in human
      clitoris.
AB  - PURPOSE: Our aim was to identify and localize nitric oxide synthase isoforms in
      the human clitoris in support of the hypothesis that nitric oxide mediates
      erectile function in this organ. MATERIALS AND METHODS: Nitric oxide synthase
      immunohistochemistry studies specific for neuronal, inducible and endothelial
      isoforms of the enzyme were performed on human clitoral tissue obtained from 4
      patients (3 with female pseudohermaphroditism and 1 with true hermaphroditism) at
      feminizing genitoplasty and from 1 phenotypically normal woman at autopsy.
      RESULTS: Neuronal nitric oxide synthase immunoreactivity was detected in nerve
      bundles and fibers coursing within the glans clitoris and corpora cavernosa of
      the clitoris, predominating in the latter tissue. Specific inducible nitric oxide
      synthase immunoreactivity was not identified. Endothelial nitric oxide synthase
      immunoreactivity was detected in vascular and sinusoidal endothelium of these
      tissues with a predominance in the glans clitoris. CONCLUSIONS: The presence and
      anatomical localizations of nitric oxide synthase isoforms in the human clitoris
      indicate that nitric oxide is generated in this organ. These data suggest that
      nitric oxide may be involved in the erectile physiology of the clitoris as a
      modulator of clitoral smooth muscle activity. Functional studies are required to
      support this hypothesis.

PMID- 9186327
TI  - Deoxyribonucleic acid flow cytometry in the assessment of spermatogenesis.
AB  - PURPOSE: We compared deoxyribonucleic acid (DNA) flow cytometric analysis of
      testicular tissue to quantitative assessment of spermatogenesis. MATERIALS AND
      METHODS: We studied 35 infertile men with azoospermia or oligospermia. All
      patients underwent incisional testicular biopsies. DNA flow cytometric analysis
      was performed on each specimen to evaluate the ability of the method to quantify
      alterations in spermatogenesis. The results were compared to quantitative
      histological examination. At least 100 spermatic tubules were examined on each
      specimen and the number of spermatids per tubule was counted. All histological
      specimens were examined by the same pathologist. RESULTS: Of the 35 specimens
      analyzed with DNA flow cytometry 5 were normal, while the percentage of haploid
      cells (spermatids and spermatozoa) was decreased (hypospermatogenesis) in 14,
      complete maturation arrest was noted in 2 and almost complete absence of haploid
      cells was found in 14. Comparing the findings on histological examination with
      histograms, excellent correlation was noted in cases of the Sertoli-cell-only
      syndrome and complete maturation arrest, while 3 of 14 histograms with
      hypospermatogenesis demonstrated normal spermatogenesis on histological
      examination. Additionally 1 of 5 histograms with norma, spermatogenesis
      demonstrated hypospermatogenesis on histological examination. CONCLUSIONS: DNA
      flow cytometry of the testicular tissue seems to be an objective and quantified
      method that can be used to investigate spermatogenesis in infertile men. It is
      also less time-consuming than any histological examination, permits management
      decisions within 1.5 hours after biopsy and may replace testicular
      histopathological study. Flow cytometric diagnoses correlated well with
      histopathological findings.

PMID- 9186328
TI  - Image analysis assessment of the abnormal testis biopsy in male infertility.
AB  - PURPOSE: We previously demonstrated that testis biopsy image analysis is an
      effective method for quantifying intratubular spermatogenic cells in the
      obstructed testis with normal spermatogenesis. As an extension of the initial
      report, we describe using the quantitative ploidy and morphological
      characteristics of cells counted with image analysis in abnormal testis biopsies
      obtained for a male infertility evaluation. MATERIALS AND METHODS: Image analysis
      using a specifically designed filter was performed on Feulgen stained 5 microns,
      sections of paraffin embedded testicular tissue. Archival testicular tissue had
      been obtained using standard biopsy techniques from patients with azoospermia or
      severe oligospermia. Qualitative classification was based on standard evaluation
      of hematoxylin and eosin processed tissue. RESULTS: There were 62 biopsies
      performed in 58 men. Significant differences in the intratubular content of
      haploid (spermatozoa and spermatids), diploid and tetraploid cells were found
      among the 5 categories of abnormalities: the Sertoli-cell-only syndrome,
      spermatocyte arrest, spermatid arrest, hypospermatogenesis and normal
      spermatogenesis. Moderate variability was found in the proportion of cell types
      in spermatid arrest and hypospermatogenesis. CONCLUSIONS: Testis biopsy image
      analysis provides a quantitative method for categorizing abnormalities of
      intratubular cell content present in male infertility states by using
      deoxyribonucleic acid content and morphology characteristics. The limitations of
      the present qualitative analysis system are emphasized by the moderate
      variability evident within the current categories of spermatid arrest and hypo
      spermatogenesis states.

PMID- 9186329
TI  - Total prostate and transition zone volumes, and transition zone index are poorly
      correlated with objective measures of clinical benign prostatic hyperplasia.
AB  - PURPOSE: We determined if total prostate volume, transition zone volume or
      transition zone index is correlated with the severity of clinical benign
      prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 93 men 52 to 85
      years old, who were referred to a urology outpatient facility for treatment of
      clinical BPH, elevated serum prostate specific antigen or abnormal digital rectal
      examination, underwent measurement of total prostate and transition zone volume
      at transrectal ultrasonography. All men were requested to undergo uroflowmetry
      and complete the American Urological Association (AUA) symptom score. RESULTS:
      The pairwise correlations between AUA symptom score, versus total prostate and
      transition zone volumes and transition zone index were not statistically or
      clinically significant. A weak pairwise relationship was observed between peak
      flow rate versus total prostate volume (r2 = 0.160), transition zone volume (r2 =
      0.156) and transition zone index (r2 = 0.147). The pairwise relationships between
      AUA symptom scores versus all prostate volumes were not statistically significant
      for subjects with mild (score 8 or less) or moderate to severe (score more than
      8) symptoms. CONCLUSIONS: Total prostate and transition zone volumes, and
      transition zone index are not directly related to AUA symptom score and only
      weakly related to peak flow rate. These findings provide further evidence that
      the total prostate, total BPH and relative BPH volumes are not useful
      determinants of the severity of clinical BPH.

PMID- 9186330
TI  - Reversible change of bladder hypertrophy due to benign prostatic hyperplasia
      after surgical relief of obstruction.
AB  - PURPOSE: Ultrasound estimated bladder weight was compared before and after
      surgery for benign prostatic hyperplasia (BPH) to reveal a possible reversible
      change in bladder hypertrophy. MATERIALS AND METHODS: Ultrasound estimated
      bladder weight was measured before and after subcapsular (17) or transurethral
      (16) prostatectomy in 33 male patients with BPH. Sequential changes in the
      American Urological Association symptom score and urinary flow rate were also
      examined. RESULTS: Along with a significant improvement in the American
      Urological Association symptom scores and maximum flow rate, ultrasound estimated
      bladder weight decreased from 52.9 +/- 22.6 to 31.6 +/- 15.8 gm. in 12 weeks
      after treatment. In all but 4 patients (29 of 33, or 87.9%) ultrasound estimated
      bladder weight decreased to less than 35.0 gm. in 12 weeks after treatment.
      Interestingly, in all patients with an initial ultrasound estimated bladder
      weight of greater than 80 gm. the bladder weight still remained at an abnormally
      high level 12 weeks after treatment. CONCLUSIONS: Bladder hypertrophy was
      completely reversible after the surgical treatment of the obstruction in the
      majority of patients with BPH. The measurement of ultrasound estimated bladder
      weight was of value in monitoring therapeutic effects in BPH patients. An
      extraordinarily high ultrasound estimated bladder weight of 80 gm. or more might
      suggest degenerative and irreversible pathological changes in the bladder
      detrusor.

PMID- 9186331
TI  - Does evaluation with the International Prostate Symptom Score predict the outcome
      of transurethral resection of the prostate?
AB  - PURPOSE: We determined the reliability of the International Prostate Symptom
      Score (I-PSS) in predicting the outcome of transurethral prostatectomy and,
      therefore, how useful it can be in patient selection for surgery. MATERIALS AND
      METHODS: A prospective trial was done of 105 consecutive patients undergoing
      transurethral prostatectomy at our institution. Patients were assessed with the I
      PSS before and 3 months after surgery. Flow rates and preoperative residual
      volumes also were measured. RESULTS: There was significant postoperative
      improvement in all parameters of the symptom score and a change in symptom
      profile. Symptoms remaining with the greatest scores at 3 months postoperatively
      were frequency, urgency and nocturia. A significant correlation was found between
      I-PSS and quality of life before and after transurethral prostatectomy, and
      between postoperative improvement in flow rates and change in I-PSS. Patients
      with a greater preoperative I-PSS gained the most symptomatic benefit. The
      positive predictive value of a significant postoperative improvement of at least
      7 I-PSS points depended on the preoperative I-PSS criteria applied. With a
      preoperative I-PSS of more than 17 the positive predictive value was 87% with a
      corresponding negative predictive value of 71%. CONCLUSIONS: The preoperative I
      PSS predicted a symptomatic improvement of more than 7 points with high
      sensitivity. The predictive value depends on the definition of significant
      improvement (magnitude of I-PSS change) and the level of I-PSS symptoms defined
      as sufficient to warrant transurethral prostatectomy.

PMID- 9186332
TI  - Benign prostatic hyperplasia.

PMID- 9186333
TI  - The safety of transurethral prostatectomy: a cohort study of mortality in 9,416
      men.
AB  - PURPOSE: We assessed the mortality rate from transurethral resection of the
      prostate. MATERIALS AND METHODS: From 1976 to 1984, 4,708 patients undergoing
      transurethral resection of the prostate for benign prostatic hypertrophy (BPH)
      were compared retrospectively to an age-matched group of 4,708 randomly selected
      Kaiser Permanente Medical Care Program members not undergoing surgery. The risk
      of mortality associated with transurethral resection of the prostate relative to
      no surgery was determined using proportional hazards models. RESULTS: The
      relative risk for surgery versus no surgery for the total group was 0.88 (95%
      confidence interval 0.82 to 0.95). Similarly, the results for each 5-year age
      group demonstrated a relative risk of 0.77 to 0.95. CONCLUSIONS: This cohort
      study showed no excess mortality for patients undergoing transurethral resection
      of the prostate compared to age-matched comparison subjects randomly selected
      from health plan members who did not undergo surgery. Information from this study
      about the safety of transurethral resection of the prostate can be shared with
      patients when discussing treatment options.

PMID- 9186334
TI  - The early postoperative morbidity of transurethral resection of the prostate and
      of 4 minimally invasive treatment alternatives.
AB  - PURPOSE: We compared the early postoperative morbidity of transurethral resection
      of the prostate to minimally invasive treatment alternatives with respect to the
      objective rate of complications and subjective morbidity assessed by a patient
      addressed diary-type questionnaire. MATERIALS AND METHODS: Parameters evaluated
      preoperatively were the International Prostate Symptom Score (I-PSS), free flow
      study, post-void residual, transrectal ultrasonography and a pressure-flow study.
      The patients underwent transurethral resection (28), transrectal high intensity
      focused ultrasound (20), visual laser ablation (15), transurethral needle
      ablation (15) and transurethral electrosurgical vaporization (17) of the
      prostate. On the day of hospital discharge the patients received the
      questionnaire and were asked to answer daily 7 questions concerning micturition
      status. After 6 weeks the questionnaire was returned and an I-PSS, uroflowmetry
      and post-void residual were obtained. RESULTS: Preoperatively, there was no
      statistically significant difference regarding the I-PSS, peak flow rate,
      prostate volume and degree of bladder outlet obstruction. After 6 weeks the peak
      flow rate improved most prominently after transurethral electrosurgical
      vaporization (+ 13.2 ml. per second), transurethral resection of the prostate (+
      12.3 ml. per second) and visual laser ablation (+ 11.1 ml. per second). The I-PSS
      decreased most significantly after transurethral resection (-14.1) and
      transurethral electrosurgical vaporization (-8.4). There was no difference
      regarding the rate of adverse events within the first 6 weeks postoperatively in
      the 5 treatment arms. Mean duration of catheter drainage plus or minus standard
      deviation was 3.7 +/- 1.2 days after transurethral resection of the prostate, 6.8
      +/- 1.7 days after high intensity focused ultrasound, 7.8 +/- 1.5 days after
      visual laser ablation, 2.0 +/- 0.4 days after transurethral needle ablation and
      3.3 +/- 0.8 days after transurethral electrosurgical vaporization. Analysis of
      the questionnaire revealed that the daytime frequency, degree of hematuria and
      incontinence were comparable for all 5 procedures within the first 6 weeks
      postoperatively. Postoperative dysuria was greatest after visual laser ablation
      and transurethral electrosurgical vaporization. Regarding the degree of nocturia,
      there was no improvement after visual laser ablation, while the remaining 4
      procedures yielded a significant and comparable decrease. The most significant
      subjective improvement in uroflowmetry was reported after transurethral resection
      of the prostate and transurethral electrosurgical vaporization. Regarding the
      global quality of life question, the patients were generally more worried after
      visual laser ablation and transurethral needle ablation compared to the other 3
      procedures. CONCLUSIONS: The overall morbidity of transurethral resection of the
      prostate within the first 6 weeks postoperatively is equivalent to that of the 4
      minimally invasive treatment alternatives evaluated in our study. When comparing
      the 4 minimally invasive procedures, no dramatic differences were notable,
      although visual laser ablation seems to be associated with a greater degree of
      morbidity as assessed by this questionnaire.

PMID- 9186335
TI  - A novel transurethral microwave thermal ablation system to treat benign prostatic
      hyperplasia: results of a prospective multicenter clinical trial.
AB  - PURPOSE: We evaluated the efficacy, safety and impact on quality of life of a
      newly designed microwave thermal ablation system in patients with benign
      prostatic hyperplasia (BPH). MATERIALS AND METHODS: Microwave thermal ablation
      was administered to 154 BPH patients at 3 centers in Canada and the United
      Kingdom during a single 1 to 2-hour office or clinic procedure without general or
      regional anesthesia and without need for potent medications necessitating
      intensive patient monitoring. Various measures of symptoms, voiding function and
      patient quality of life were assessed at baseline, 6 weeks, and-3, 6, 9 and 12
      months after treatment. RESULTS: Mean American Urological Association symptom
      score 12 months after treatment (8.8, 95% confidence interval 7.7 to 10.0) was
      significantly lower (p < 0.05) by 56% than that at baseline (20.1, 95% confidence
      interval 19.1 to 21.0). The incidence of mild symptoms increased from 0 to 57%,
      while that of severe symptoms decreased from 49 to 8%. There was a significant
      increase (p < 0.05) in peak flow rate of 45% from 9.3 ml. per second (95%
      confidence interval 8.8 to 9.7) at baseline to 13.4 ml. per second (95%
      confidence interval 12.5 to 14.4) at 12 months. Similar symptomatic and
      urodynamic improvements occurred in all prostate volume categories. Convalescence
      was rapid after treatment with little or no need for home bed rest or restriction
      of usual activities. Patients expressed a high level of satisfaction with
      treatment and found the prostate symptoms to be significantly more tolerable.
      Adverse events were infrequent, transient and readily managed. CONCLUSIONS:
      Microwave thermal ablation proved to be safe and effective for treatment of BPH
      with a significant positive impact on patient quality of life.

PMID- 9186336
TI  - High energy thermotherapy versus transurethral resection in the treatment of
      benign prostatic hyperplasia: results of a prospective randomized study with 1
      year of followup.
AB  - PURPOSE: We compared the outcome of transurethral resection of the prostate and
      high energy microwave thermotherapy in patients with benign prostatic
      hyperplasia. MATERIALS AND METHODS: Of 52 patients with symptomatic benign
      prostatic hyperplasia 21 (mean age plus or minus standard deviation 69.6 +/- 8.5
      years) were treated with transurethral resection of the prostate and 31 (mean age
      69.3 +/- 5.9 years) were treated with high energy microwave thermotherapy.
      Patients were assessed using the Madsen symptom score, measurements of voiding
      parameters, transrectal ultrasound and cystometry, including pressure-flow
      analyses. Examinations were repeated at fixed intervals for up to 12 months after
      treatment. RESULTS: After transurethral resection and thermotherapy there was
      significant improvement in all clinical parameters. At 1 year of followup
      symptomatic improvement was 78% in the transurethral resection group versus 68%
      in the thermotherapy group, with improvements in free flow rate of 100 and 69%,
      respectively. Both groups had significant relief of bladder outlet symptoms. No
      serious complications occurred in either group, while 1 patient in each group
      required repeat treatment. CONCLUSIONS: Satisfactory results were obtained after
      both treatments, with improvements following high energy microwave thermotherapy
      being in the same range as those after transurethral resection of the prostate.

PMID- 9186337
TI  - Transrectal ultrasound appearance of prostatic granulomas secondary to bacillus
      Calmette-Guerin instillation.
AB  - PURPOSE: To our knowledge the transrectal ultrasound appearance of prostatic
      granulomas occurring after intravesical bacillus Calmette-Guerin (BCG) therapy
      has not been thoroughly described. MATERIALS AND METHODS: A total of 13 men with
      a history of transitional cell carcinoma of the bladder treated with intravesical
      BCG underwent transrectal ultrasound followed by prostate biopsy and/or
      cystoprostatectomy. RESULTS: Of the 13 patients studied 9 (69.2%) had intensely
      hypoechoic lesions anteriorly in the transition zone of the prostate on
      ultrasound images. The lesions were histologically proved to be necrotizing
      granulomas. CONCLUSIONS: Prostatic granulomas secondary to BCG instillation
      appear as distinct, intensely hypoechoic anterior lesions within the transition
      zone of the prostate. Prostatic adenocarcinoma arising in the transition zone is
      usually not visible and would not be easily confused with granulomas. However,
      since transitional cell carcinoma involving the prostate can appear hypoechoic in
      the transition zone, transrectal or transurethral tissue sampling may be
      indicated.

PMID- 9186338
TI  - Hip and knee replacement as a relative contraindication to laparoscopic pelvic
      lymph node dissection.
AB  - PURPOSE: We investigated the effect of lower extremity joint prostheses on
      subsequent laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS: We
      reviewed the records and pathology studies of 5 patients who underwent
      laparoscopic pelvic lymph node dissection subsequent to total hip or knee
      replacement from 1990 through 1995. RESULTS: Four of the 5 laparoscopic
      operations were complicated, 3 were unsuccessful in obtaining bilateral pelvic
      lymph nodes and 2 required conversion to an open procedure. Examination of the
      lymph nodes revealed sinus histiocytosis in the 4 cases in which nodal tissue was
      removed. CONCLUSIONS: The increased risk of complications in certain patients
      with lower extremity joint prostheses may contraindicate attempted laparoscopic
      pelvic lymph node dissection.

PMID- 9186339
TI  - p53, bcl-2 and retinoblastoma proteins as long-term prognostic markers in
      localized carcinoma of the prostate.
AB  - PURPOSE: The accumulation of p53 and bcl-2 gene products as well as the loss of
      the retinoblastoma (Rb) gene product have been associated with prostate cancer
      progression. We assessed whether the levels of immunoreactivity for p53, Rb and
      bcl-2 are better long-term predictors of disease specific survival than
      conventional pathological parameters of the primary tumor, such as Gleason score,
      capsular penetration, seminal vesicle invasion and percent tumor in the specimen,
      in patients with clinically localized prostate cancer treated with radical
      prostatectomy. MATERIALS AND METHODS: A total of 71 patients with clinical stages
      A1 to B2 adenocarcinoma of the prostate underwent radical prostatectomy after a
      negative metastatic evaluation. No neoadjuvant or adjuvant treatments were given
      and causes of death were recorded. Prostatectomy specimens were analyzed to
      determine the conventional pathological parameters, and p53, Rb and bcl-2
      immunohistochemical staining. Univariate and multivariate analyses were done to
      determine the independent contributions of p53, Rb and bcl-2 in predicting
      survival. RESULTS: On multivariate analysis the independent factors predicting
      disease specific survival were p53 staining score (p < 0.001) and Rb staining
      score (p < 0.001). In patients with p53 immunoreactive tumors the 15-year disease
      specific survival was 38% compared to 87% for those with less immunoreactivity.
      Analysis of Rb immunoreactivity for 15-year disease specific survival yielded 92
      and 66% high and low staining levels, respectively. Best subset analysis revealed
      that the combination of p53 score and Rb score yielded the best predictive value
      for disease specific survival. CONCLUSIONS: p53 and Rb immunohistochemical
      staining scores were independent predictors of disease specific survival and were
      superior to conventional pathological prognostic factors of the primary tumor.
      These findings lay the groundwork for the prospective study of these markers in
      patients treated with radical prostatectomy.

PMID- 9186340
TI  - Transurethral biopsy of the prostate for persistently elevated or increasing
      prostate specific antigen following multiple negative transrectal biopsies.
AB  - PURPOSE: Treatment of the patient with persistently elevated prostate specific
      antigen (PSA) levels after pathologically negative transrectal or manually
      directed prostate needle biopsy is unclear. We retrospectively evaluated the use
      of transurethral biopsy of the prostate as an adjunctive study for the diagnosis
      of prostate cancer in these patients. MATERIALS AND METHODS: From January 1993
      through February 1996, 71 patients underwent transurethral biopsy in conjunction
      with repeat prostatic needle biopsy for a persistently elevated PSA (greater than
      4 ng./ml.) after previously negative needle biopsy. All patients had at least 1
      previous ultrasound guided sextant prostatic needle biopsy (mean 1.85, range 1 to
      7) with or without manually directed biopsies. Following negative prostatic
      needle biopsy these patients subsequently underwent a minimum of a 4-quadrant
      transurethral sampling of the prostatic fossa followed by repeat sextant
      prostatic needle biopsy. A subset of patients underwent sampling of the anterior
      prostatic tissue or transition zone using transrectal ultrasound guided prostatic
      needle biopsy at transurethral biopsy. RESULTS: Of the 71 patients with elevated
      PSA (mean 16.2 ng./ml., range 4.2 to 171) 17 (24%) had prostate cancer on the
      repeat prostatic needle biopsy. Both patients who had prostate cancer on the
      transurethral biopsy specimens also had prostate cancer on the repeat prostatic
      needle biopsy specimens. A total of 68 patients had benign prostatic tissue and 1
      had high grade prostatic intraepithelial neoplasia on transurethral biopsy
      specimens. Of 19 patients with high grade prostatic intraepithelial neoplasia on
      the initial prostatic needle biopsy, transurethral biopsy specimens revealed no
      prostate cancer or prostatic intraepithelial neoplasia. Repeat prostatic needle
      biopsy in these patients with high grade prostatic intraepithelial neoplasia
      revealed prostate cancer in 6 and high grade prostatic intraepithelial neoplasia
      in 4. CONCLUSIONS: In patients with persistently elevated or increasing serum PSA
      after a previously negative prostatic needle biopsy, transurethral biopsy is not
      a useful adjunct in diagnosing prostate cancer. In this high risk group of
      patients transurethral biopsy adds little or no diagnostic value to prostatic
      needle biopsy even in those with high grade prostatic intraepithelial neoplasia.

PMID- 9186341
TI  - Statistical review and analysis of the relationship between serum prostate
      specific antigen and age.
AB  - PURPOSE: We investigated the possibility that the variations in the reported
      correlation coefficient (r) between age and serum prostate specific antigen (PSA)
      is simply a reflection of the differences in the age mix of the population
      studied, that is the younger the population the greater the correlation and vice
      versa. Also, we quantified the value of r for different age groups to evaluate
      finally the plausibility of its practical application on sound statistical basis.
      MATERIALS AND METHODS: Bivariate and multivariate regression analyses were done
      of all identified reports in the literature that specified the exact value of r
      and the percentage distribution of the population studied in 10-year age groups.
      RESULTS: The correlation coefficient between r and the percentage of the
      population in different age groups was statistically significant, confirming the
      hypothesis that the greater the percentage of younger population in the study,
      the greater the value of r and vice versa. The correlation between age and PSA
      did change with age. It was significantly high in the fifth to sixth decades of
      life (range 0.5 to 0.7) [corrected] and markedly decreased in decade 7 to become
      low and insignificant in decade 8. CONCLUSIONS: The value of the correlation
      between age and PSA is sufficiently high to allow for its practical application
      up to age 60 years. Beyond that age the correlation is so low that its practical
      application becomes statistically flawed. This finding seems to match the
      practical experience when applying age-specific PSA ranges in the diagnosis of
      early prostate cancer.

PMID- 9186342
TI  - Outcome of African American men screened for prostate cancer: the Detroit
      Education and Early Detection Study.
AB  - PURPOSE: Will early detection impact on stage of disease and recurrence of
      prostate cancer in a high risk population? We initiated a community based study
      to educate and recruit African American men for early diagnosis of prostate
      cancer, that is the Detroit Education and Early Detection (DEED) study. Our
      objective was to evaluate our recruitment process for this target population,
      examine the percentage of organ confined prostate cancer in men undergoing
      radical prostatectomy and measure recurrence biochemically. MATERIALS AND
      METHODS: A community based study from February 1993 to February 1995 through the
      African American churches in metropolitan Detroit was initiated. We compared the
      early detection group treated with radical prostatectomy to the population
      presenting to our urological clinic during the same period. We tested and
      followed 1,105 African American men using the prostate specific antigen blood
      test. RESULTS: Pathologically organ confined prostate cancer was diagnosed in 11
      of 17 men (65%) who underwent radical prostatectomy in the DEED project. Within
      the clinic population 35% of the African American men were diagnosed with
      pathologically organ confined prostate cancer. The difference between the 2
      populations was statistically significant (p = 0.033). Disease recurred in 1 of
      15 (7%) and 39 of 157 (25%) men in the DEED and clinic populations, respectively
      (p = 0.97). CONCLUSIONS: We demonstrated our ability to recruit African American
      men into a prostate cancer early detection program. We diagnosed early but
      clinically significant prostate cancers among African American men with
      characteristics similar to prostate cancers diagnosed in other early detection
      studies in which the overwhelming majority of men were white.

PMID- 9186343
TI  - Prostate specific antigen in black and white men after hormonal therapies for
      prostate cancer.
AB  - PURPOSE: Prostate cancer deaths usually result from proliferation of the androgen
      independent malignant phenotype, and in the United States the survival of black
      men with metastatic cancer is less favorable than that of white men. We compared
      prostate specific antigen (PSA) functions after hormonal therapies in men of both
      races to investigate potential differences in the biology of androgen independent
      cancer. MATERIALS AND METHODS: The PSA nadir after gonadal androgen withdrawal
      was determined in 217 black and 188 white men with localized or metastatic
      cancer. The time to PSA elevation and PSA doubling time were determined in 62
      black and 27 white men with biochemical relapse. Biochemical response to deferred
      flutamide treatment and flutamide withdrawal was assessed in 87 and 11 black and
      30 and 10 white men, respectively. RESULTS: There were no significant racial
      differences in the PSA nadir when controlled for clinical stage and pretreatment
      PSA, or in PSA doubling time when controlled for clinical stage, PSA nadir and
      month of PSA elevation. The biochemical response to deferred flutamide therapy
      and flutamide withdrawal was the same in black and white men. CONCLUSIONS: The
      burden and growth rate of androgen independent cancer estimated from PSA
      functions after gonadal androgen withdrawal, and the impact of deferred
      antiandrogen therapy on the serum PSA are similar in black and white men. These
      findings suggest that racial differences in the biology of androgen independent
      carcinoma do not contribute to the inferior survival of black men with metastatic
      prostate cancer.

PMID- 9186344
TI  - Factors associated with waning sexual function among elderly men and prostate
      cancer patients.
AB  - PURPOSE: We identified factors that affect sexual function in men 50 to 80 years
      old and, therefore, may confound the comparison among groups of elderly men. In
      particular, we identified factors that may influence a comparison between
      prostate cancer patients and the general population, or confound the relationship
      when comparing subgroups of patients in nonrandomized studies. MATERIALS AND
      METHODS: A questionnaire, including the Radiumhemmet Scale of Sexual Function and
      modules assessing potential risk factors for waning sexual function, was sent to
      431 patients 50 to 80 years old with prostate cancer diagnosed 1.5 to 2 years
      previously in the Stockholm area (Sweden) and a reference group of 435 age
      matched randomly selected men. RESULTS: Factors associated with physiological
      impotence included prostate cancer (relative risk 1.9), diabetes mellitus
      (relative risk 2.3), myocardial infarction (relative risk 1.5), medication with
      diuretics (relative risk 1.5), hydrogen blockers (relative risk 2.3) and warfarin
      type anticoagulants (relative risk 1.7). Patients treated for prostate cancer
      were more likely to be physiologically impotent compared to those with no initial
      treatment, and this was true for all treatment protocols after adjustment for
      confounding factors. Men treated with radical prostatectomy were more likely to
      be physiologically impotent than men treated with external beam radiation therapy
      (relative risk 1.5). CONCLUSIONS: Waning sexual function in the prostate cancer
      patients was largely due to side effects of the treatment and this could not be
      explained by confounding factors. In particular, confounding could not explain
      the greater risk of impotence after radical prostatectomy compared to external
      beam radiation therapy.

PMID- 9186345
TI  - Long-term efficacy and safety of nilutamide plus castration in advanced prostate
      cancer, and the significance of early prostate specific antigen normalization.
      International Anandron Study Group.
AB  - PURPOSE: We studied the long-term efficacy and tolerability of nilutamide, a
      nonsteroidal antiandrogen, combined with orchiectomy in patients with advanced
      prostate cancer. MATERIALS AND METHODS: A large double-blind trial was done on
      457 patients randomized to receive nilutamide or placebo after orchiectomy.
      RESULTS: At 8.5 years of followup significant benefits were found for progression
      and survival in favor of patients receiving nilutamide and orchiectomy. In
      addition, normalized prostate specific antigen levels at 3 months from the start
      of therapy were predictive of good long-term outcome. Moreover, combined androgen
      blockade with nilutamide increased the chance of patients having normal prostate
      specific antigen levels at 3 months. Nilutamide was well tolerated in the long
      term with no increase in the incidence of drug specific adverse events.
      CONCLUSIONS: With long-term followup of patients with advanced prostate cancer,
      the combination of nilutamide and orchiectomy has significant benefits in
      interval to progression and improved survival compared to orchiectomy and
      placebo.

PMID- 9186346
TI  - Prognostic factors in patients with metastatic (stage D2) prostate cancer:
      experience from the Scandinavian Prostatic Cancer Group Study-2.
AB  - PURPOSE: Nuclear texture reflects the overall structures of the chromatin
      organization. We recently reported the principles and prognostic importance of
      image analysis of nuclei from metastatic prostate cancer. Immunohistochemical up
      regulation of the adhesion molecule sialyl Lewis(x) is also reported to be a
      prognostic parameter. Presently we analyzed statistically the prognostic impact
      of these 2 new parameters compared to well-known clinical parameters in
      metastatic prostate cancer. MATERIALS AND METHODS: Prognostic factors, such as
      sedimentation rate, alkaline and acid phosphatases, hemoglobin, testosterone,
      performance status, pain due to metastasis, T category, histological grade and
      patient age, were included in a multivariate Cox proportional hazards regression
      analysis based on 262 patients from the Scandinavian Prostatic Cancer Group Study
      2. Extent of bone lesions, deoxyribonucleic acid ploidy, texture analysis and
      sialyl Lewis(x) molecules based on subsets of these 262 patients were also
      analyzed in the same multivariate model. RESULTS: This test identified chromatin
      texture as the most important factor (p < 0.001), followed by reaction of the
      oligosaccharide sialyl Lewis(x) (p < 0.01). Among the routine clinical and
      laboratory data, sedimentation rate, alkaline phosphatase and hemoglobin (p <
      0.05) showed prognostic importance. Performance status, pain due to metastasis
      and extent of bone lesions showed prognostic value in the univariate analysis (p
      < 0.05). CONCLUSIONS: These data indicate that computerized nuclear texture
      analysis as well as up regulation of sialyl Lewis(x) molecules may be new
      important prognostic factors in metastatic prostate cancer. Furthermore the
      prognostic importance of sedimentation rate, alkaline phosphatase and hemoglobin
      was confirmed.

PMID- 9186347
TI  - The prognostic value of neuroendocrine differentiation in adenocarcinoma of the
      prostate in relation to progression of disease after endocrine therapy.
AB  - PURPOSE: We evaluated the prognostic impact of neuroendocrine differentiation in
      prostate cancer with regard to the onset of endocrine therapy failure. MATERIALS
      AND METHODS: A retrospective study was performed on 72 transurethral resection
      specimens from patients who subsequently underwent endocrine therapy for prostate
      cancer and were followed for 44 to 95 months. Progression-free interval was
      recorded. Distribution pattern and proportion of neuroendocrine cells were
      examined in transurethral resection specimens. Neuroendocrine cells were
      identified based on immunoreactivity for chromogranin A. RESULTS: Of 32 patients
      with progressive disease 27 died of prostate cancer. Chromogranin A positive
      cells were found in 40 of the 72 prostate cancers (55%). In a Cox proportional
      hazards analysis neuroendocrine differentiation of the tumor showed a negative
      correlation with progression-free survival (p = 0.022), which proved to be
      independent of the Gleason score (p < 0.001). CONCLUSIONS: Our results support
      the view that neuroendocrine differentiation in prostatic adenocarcinomas is a
      prognostic factor for progressive disease under subsequent endocrine therapy.
      This prognosticator acts independently of tumor grade.

PMID- 9186348
TI  - Is prednisolone as good as flutamide in hormone refractory metastatic carcinoma
      of the prostate?
AB  - PURPOSE: There are no generally accepted rules for the second line treatment of
      prostate cancer and few prospective studies have attempted to compare 2
      therapeutic strategies with different modes of action. MATERIALS AND METHODS: We
      describe a prospective, randomized study of 40 patients comparing the second line
      response of flutamide to prednisolone in patients with known hormone refractory
      stage M1 prostate cancer. RESULTS: The median survival of patients receiving
      either treatment was 32.9 weeks, with no difference between the 2 groups. In
      terms of biological response 11 of 20 patients (55%) receiving prednisolone and
      10 of 20 (50%) receiving flutamide exhibited prostate specific antigen (PSA)
      suppression. Average minimum PSA was 54 and 52% of the initial PSA in patients
      receiving prednisolone and flutamide, respectively. There was no difference
      between the 2 treatment groups in terms of long-term survival, although 35% of
      all patients survived beyond 1 year and 3 survived beyond 2 years. CONCLUSIONS:
      More patients taking prednisolone described better pain relief, although both
      medications were well tolerated and there was no difference in terms of
      performance status or analgesic requirements.

PMID- 9186349
TI  - Androgen ablation therapy--where to next?

PMID- 9186350
TI  - Transrectal ultrasound guided drainage of prostatic cysts.
AB  - PURPOSE: A technique for transrectal ultrasound guided drainage of prostatic
      cysts and large cystic utricles is described using simple adaptation of equipment
      readily available in the transrectal ultrasound suite. MATERIALS AND METHODS:
      Using the puncture trajectory display generated by the ultrasound unit, the
      biopsy needle is manually advanced through the needle guide of the transrectal
      ultrasound probe. Once the tip of the needle reaches the lumen of the cystic
      lesion, the central trocar of the needle is removed from the outer cannula and
      intravenous line tubing is inserted into the opening in the trocar. The syringe
      is attached to the opposite end of the extension tubing, allowing for cyst
      aspiration. RESULTS: This technique was performed successfully in 11 patients
      with symptomatic cysts within the prostate, including 7 with intraprostatic cysts
      and 4 with cystic utricles. The fluid collection recurred in 1 patient with a
      cystic utricle, causing epididymal pain and orchialgia that resolved with repeat
      drainage. CONCLUSIONS: This technique allows for easy, successful drainage of
      symptomatic prostatic cysts in an outpatient setting without specialized
      equipment or anesthesia.

PMID- 9186351
TI  - Urodynamic risk factors for renal dysfunction in men with obstructive and
      nonobstructive voiding dysfunction.
AB  - PURPOSE: Urodynamic investigation of men with lower urinary tract symptoms,
      usually attributed to benign prostatic hyperplasia, often reveals bladder outlet
      obstruction, detrusor instability and/or diminished vesical compliance. We
      investigated whether these urodynamic abnormalities alone or in combination
      contribute to renal dysfunction. MATERIALS AND METHODS: A total of 161 men with
      lower urinary tract symptoms was evaluated by urodynamics, and outlet
      obstruction, detrusor instability and decreased compliance (30 ml./cm. water or
      less) were noted. Serum blood urea nitrogen (BUN) and creatinine were measured.
      Cases were categorized according to the urodynamic diagnosis. Mean values of
      serum BUN and creatinine as well as the incidence of elevated BUN and creatinine
      were compared among groups. RESULTS: Of the cohort 54 men (34%) had elevated BUN
      and 19 (12%) had elevated serum creatinine. No significant correlation was found
      between the degree of obstruction and BUN or creatinine level. Mean serum BUN and
      creatinine, and the incidence of abnormal laboratory tests did not significantly
      differ among those with outlet obstruction, detrusor instability, both conditions
      or neither condition. However, in patients with outlet obstruction and detrusor
      instability there was a significantly increased incidence of azotemia in the
      subgroup with diminished compliance (78%) versus the subgroup with normal
      compliance (36%). CONCLUSIONS: In men with voiding dysfunction of a nonneurogenic
      etiology outlet obstruction with or without detrusor instability does not appear
      to be a risk factor for elevated BUN and creatinine. However, when decreased
      bladder compliance is associated with a combination of outlet obstruction and
      detrusor instability, this risk is substantially increased.

PMID- 9186352
TI  - Re: Is contralateral exploration of the kidney necessary in patients with Wilms
      tumor?

PMID- 9186353
TI  - Re: Intracorporeal lithotripsy with the holmium: YAG laser.

PMID- 9186354
TI  - Re: Alternative approaches to the prognostic stratification of mild to moderate
      primary vesicoureteral reflux in children.

PMID- 9186355
TI  - Re: Penile sensitivity in patients with primary premature ejaculation.

PMID- 9186356
TI  - Botulinum toxin: novel treatment for dramatic urethral dilatation associated with
      dysfunctional voiding.

PMID- 9186357
TI  - Combined Mitrofanoff and antegrade continence enema procedures for urinary and
      fecal incontinence.
AB  - PURPOSE: Fecal soiling or intractable constipation frequently occurs in
      association with urinary incontinence in children undergoing major reconstructive
      urological operations. To treat double incontinence or the combination of wetting
      and severe constipation, we constructed a Mitrofanoff conduit and a channel for
      antegrade continence enemas in 18 patients between 1989 and 1995. We review the
      underlying pathological conditions, various surgical techniques and outcomes of
      these operations. MATERIALS AND METHODS: Underlying abnormalities mainly included
      spinal lesions, bladder exstrophy, imperforate anus and various cloacal
      anomalies. Patient age ranged from 2 to 18 years (average 8.4). In 13 patients
      both procedures were done simultaneously. The appendix was used to construct the
      antegrade continence enema channel in 8 cases and the Mitrofanoff channel in 5.
      It was long enough to be divided and used for both procedures in 2 cases but it
      was missing or unsuitable in 3. Alternative antegrade continence enema conduits
      were cecal flap in 7 patients and ileum in 1, while the ureter, ileum and
      detrusor tube were used to establish Mitrofanoff channels in 5, 5 and 1,
      respectively. Stomas were constructed according to the V-flap or V. Z. Q.
      technique and situated in close proximity in the right lower abdominal quadrant
      in 13 cases. RESULTS: Convalescence was uneventful except for 1 abscess near an
      antegrade continence enema stoma. Ten patients needed dilation or minor revisions
      due to difficulty in catheterizing the antegrade continence enema (5),
      Mitrofanoff (3) or both conduits (2). Subsequently 3 patients underwent repeat
      operations for reconstruction of 2 antegrade continence enema channels (cecal
      flap and ileum) and 1 detrusor tube Mitrofanoff channel. Currently 15 patients
      are dry on regular clean intermittent catheterization using 10 to 12F catheters.
      Outcomes of the antegrade continence enema channels are satisfactory in 15
      patients who are clean or rarely soil. Failure occurred in 1 patients with severe
      constipation necessitating colostomy and 2 (1 noncompliant who stopped
      catheterizing regularly) in whom the channels subsequently closed. CONCLUSIONS:
      Synchronous construction of antegrade continence enema and Mitrofanoff channels
      is successful in the majority of doubly incontinent patients. Selection of
      patients with high motivation is important to obtain satisfactory results.

PMID- 9186358
TI  - A nonsurgical approach to the treatment of phimosis: local nonsteroidal anti
      inflammatory ointment application.
AB  - PURPOSE: We evaluated the effectiveness of topical application of nonsteroidal
      anti-inflammatory ointment for phimosis. MATERIALS AND METHODS: A total of 52
      children with phimosis was included in this study. Phimosis was graded according
      to severity. Of the patients 32 were given locally a nonsteroidal anti
      inflammatory ointment prepared in ophthalmic usage form from sterile diclofenac
      sodium ampules (not commercially available). The control group comprised 20
      patients given sterile petrolatum ointment. Patients were seen before and after
      treatment, and graded according to retractibility and appearance of the foreskin.
      Treatment continued for 4 weeks with 3 applications daily. RESULTS: Of the 32
      patients 24 responded to therapy and 8 remained unchanged or had insufficient
      improvement. Three controls responded to therapy and 17 did not. There were no
      side effects. CONCLUSIONS: Nonsteroidal anti-inflammatory ointment application
      for phimosis may be an alternative to surgery and steroid application.

PMID- 9186359
TI  - Mesothelioma of tunica vaginalis testis in a child.

PMID- 9186360
TI  - Teratoma in an undescended testis detected prenatally.

PMID- 9186361
TI  - Strong correlation of basement membrane degradation with p53 inactivation and/or
      MDM2 overexpression in superficial urothelial carcinomas.
AB  - PURPOSES: We investigated the relationships between the degradation of basement
      membrane underlying superficial urothelial carcinomas, including carcinoma in
      situ and the functional p53 loss caused by inactivation of p53 and the
      overexpression of mdm2 oncoprotein. MATERIALS AND METHODS: Nuclear accumulations
      of p53 and mdm2 were examined immunohistochemically for 60 transitional cell
      carcinomas (primary lesions) and 13 accompanying (concomitant) carcinoma in situ
      lesions. Degradation of the basement membrane was defined as the reduction or
      total loss of type IV collagen expression. Whether there was up-regulation of MMP
      1, MMP-2, and MMP-9 was analyzed immunohistochemically. RESULTS: The frequency of
      the degradation of basement membrane underlying grade 1 pTa tumors was 0%, grade
      2-3 pTa tumors 57.1%, and primary CIS lesions 83.3%. Nuclear over-accumulation of
      p53 was found in 48.3% and of mdm2 in 23.3% of the primary tumors. In pTa-pT1
      carcinomas, nuclear staining of p53, mdm2, or both was highly correlated with
      degradation of the basement membrane underlying carcinomas (p = 0.00002). In the
      CIS lesions, the association of p53 nuclear staining with the destruction of type
      IV collagen expression was of borderline significance (p = 0.03). When mdm2
      overexpression was considered as a molecular abnormality together with p53
      inactivation, the correlation with the degradation of the basement membrane was
      highly significant (p = 0.00006). Moreover, the functional p53 loss was strongly
      associated with the up-regulation of matrix metalloproteinases (MMPs) (p =
      0.0005). This finding was well correlated with the strong association of basement
      membrane degradation with up-regulation of MMPs (p = 0.000004). CONCLUSIONS:
      Degradation of basement membranes underlying superficial carcinomas or CIS of the
      urothelium was significantly related to p53 inactivation, mdm2 overexpression, or
      both. The expression status of mdm2 should provide better information about the
      progression of superficial urothelial carcinomas than the status of p53 alone.

PMID- 9186362
TI  - Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic
      hyperplasia after androgen deprivation.
AB  - PURPOSE: Benign prostatic hyperplasia (BPH) is related to advancing age and the
      presence of androgens and occurs in virtually all older men. BPH causes
      morbidity, most often by urinary obstruction, in a substantial fraction of men
      over sixty. Both finasteride and androgen ablation induce partial diminution in
      BPH that occurs over weeks to months. This is in contrast to the often rapid
      involution seen in both normal prostatic epithelium and prostatic carcinoma in
      response to androgen withdrawal. This study was performed to analyze the response
      of prostatic cells, and in particular BPH, to acute androgen ablation. MATERIALS
      AND METHODS: We subjected a cohort of 26 men to androgen ablation with goserelin,
      a gonadotrophin releasing hormone agonist, for 3-4 weeks prior to radical
      prostatectomy for prostate cancer. Preablation biopsy specimens and prostatectomy
      specimens were immunohistochemically stained for apoptotic cells and for
      expression of apoptosis regulatory proteins Bcl-2, Bax, Bcl-x, and Bak. RESULTS:
      Normal prostatic epithelial cells and prostate cancer responded to hormone
      deprivation by undergoing apoptosis, but in 19/26 specimens prostatic hyperplasia
      had a total absence of apoptosis. In all 26 specimens, benign prostatic
      hyperplasia demonstrated increased expression of the Bcl-2 protein, but no change
      in the expression of Bax, Bcl-x, and Bak. In contrast, adjacent normal and
      malignant prostatic epithelium showed positive staining for apoptosis and did not
      alter Bcl-2 expression in response to androgen ablation. CONCLUSIONS: BPH
      demonstrated increased staining for Bcl-2 after androgen deprivation that may
      render hyperplastic epithelium relatively resistant to apoptosis induced acutely
      by androgen withdrawal.

PMID- 9186363
TI  - Cell kinetic in epithelium and stroma of benign prostatic hyperplasia.
AB  - The induction of benign prostatic hyperplasia (BPH) from normal prostate is
      obviously associated with a distinct increase in epithelial and stromal
      proliferation. We have shown previously that the further increase of BPH volume
      in aging men is not associated with a further increase in proliferation. We
      studied whether an imbalance between programmed cell death (apoptosis) and cell
      proliferation may explain continuing growth in aging men. In prostates of 17 men
      with BPH removed by open prostatectomy proliferating cells were localized
      immunohistochemically with the Ki-67 antibody. Apoptotic cells were detected with
      the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) method. Proliferation and apoptotic index was calculated with a computer
      assisted image analysis system. Mean proliferation index +/- standard deviation
      in epithelium (0.142 +/- 0.097) and stroma (0.121 +/- 0.082) was nearly
      identical. Mean apoptotic index in epithelium (0.172 +/- 0.156) was negligibly
      higher than the corresponding proliferation index. In stroma, however, no
      apoptotic cells were detectable. Proliferation index and apoptotic index in
      epithelium and proliferation index in stroma showed no correlation to patient age
      or prostate volume. In the epithelium of BPH, obviously the cell kinetic is
      balanced. On the other hand, our results indicate stromal growth due to cell
      proliferation in the absence of cell death. This may explain the continuous
      increase of BPH volume in aging men.

PMID- 9186364
TI  - Systemic administration of insulin-like growth factor I (IGF-I) causes growth of
      the rat prostate.
AB  - PURPOSE: To investigate the effects of insulin-like growth factor I (IGF-I) and
      epidermal growth factor (EGF) on the rat prostate. In addition, we investigated
      the effect of ornithine decarboxylase (ODC) inhibition with alpha
      diflouromethylornitine (DFMO) on the expected growth of the prostate. MATERIALS
      AND METHODS: Eight week old Wistar rats were allocated into groups of eight,
      receiving systemic treatment for 3 and 7 days with either IGF-I (400
      micrograms/rat/day) or EGF (30 micrograms/rat/day) alone or in combination with
      DFMO. RESULTS: Systemic treatment with IGF-I for 7 days resulted in a 29% (p <
      0.01) increase in the mean wet weight of the ventral prostate. The mean weight of
      the dorsolateral lobe of the prostate increased by 39% (p < 0.05), and the
      seminal vesicle and coagulating gland increased 69% (p < 0.05) compared to
      controls. The ODC-activity in the prostate was significantly increased by IGF-I
      after 3 days of treatment, and administration of IGF-I concomitantly with DFMO
      significantly inhibited ODC activity and the weight increase of the prostate.
      Stereological examination of the prostate in the IGF-I-treated animals showed
      growth of the epithelial component of the gland. Systemic treatment with EGF did
      not affect the mean weight of the prostate or the seminal vesicle compared to
      controls. CONCLUSION: The results demonstrate that treatment with IGF-I but not
      EGF for 7 days induces profound growth of the rat prostate and the seminal
      vesicle, and that the growth is dependent on an intact ODC-activity.

PMID- 9186365
TI  - Electromotive administration of oxybutynin into the human bladder wall.
AB  - PURPOSE: To compare concentrations of oxybutynin in the human bladder wall after
      either passive delivery (PD) or electromotive administration (EMDA). MATERIALS
      AND METHODS: Tissue sections of human bladder were inserted into a diffusion cell
      with urothelium exposed to the donor compartment containing oxybutynin (4.5 mg.
      in 100 ml. NaCl 0.45%) and an anode. Twelve paired experiments, "current 5 mA/no
      current", were conducted over 15 minutes. Oxybutynin tissue contents were
      measured and tissue viability, morphology and oxybutynin stability were assessed.
      RESULTS: Mean oxybutynin tissue concentrations were 3.84 micrograms./gm. in
      samples exposed to EMDA and 0.87 microgram./gm. in samples exposed to PD (p =
      0.0006). The mean coefficients of variation were 57.85% in EMDA experiments and
      89.78% in PD experiments. Tissues were viable and undamaged histologically and no
      oxybutynin structural modification was observed. CONCLUSIONS: EMDA enhances
      oxybutynin administration into viable bladder wall and reduces the variability in
      drug delivery rate.

PMID- 9186366
TI  - Contractility changes of the deep dorsal penile vein due to serotonin.
AB  - PURPOSE: Penile erection is a complex neurovascular phenomenon that takes place
      with the active contribution of arterial and sinusoidal structures. However, some
      authors claim that larger veins including the deep dorsal veins that produce
      contractions, might be involved in the physiology of erection. This study was
      designed to clarify the contractile properties of deep dorsal penile veins
      (DDPV). MATERIALS AND METHODS: The effect of serotonin (5-HT), noradrenaline
      (NA), adenosine triphosphate (ATP) and acethylcholine (Ach) on the isolated DDPVs
      of 16 impotent men, 9 with veno-occlusive dysfunction and 7 without venous
      leakage, and 5 potent men (controls) who underwent radical prostatectomy, were
      examined in vitro. RESULTS: Although NA, ATP and Ach had no effect, 5-HT produced
      concentration-dependent contractions. Emax and pEC50 of 5-HT were 411 +/- 10 mg.,
      5.92 +/- 0.25; 1020 +/- 260 mg., 5.83 +/- 0.24 and 160 +/- 40 mg., 6.4 +/- 0.22
      in controls and patients who had venous leakage and no venous leakage,
      respectively. Samples of controls were contracted only with 5-HT2 agonist, DOI
      (pEC50 = 5.63 +/- 0.02), and these contractions were antagonized with 5-HT2
      antagonist ketanserin. On the other hand, both DOI (pEC50 = 6.30 +/- 0.77) and 5
      HT1 agonist, 5-CT (pEC50 = 6.23 +/- 0.21) produced venoconstriction in patients
      with veno-occlusive dysfunction. CONCLUSIONS: The present findings suggest that 5
      HT receptor functions in the DDPVs are of 5-HT2 subtype in potent men and the
      altered response to 5-HT in patients with veno-occlusive disease may play a role
      in the pathophysiology of impotence.

PMID- 9186367
TI  - Participation of paraventricular nucleus of hypothalamus in central regulation of
      penile erection in the rat.
AB  - PURPOSE: To investigate the possible participation of the paraventricular nucleus
      of hypothalamus in central regulation of penile erection. MATERIALS AND METHODS:
      Male adult Sprague-Dawley rats were anesthetized and maintained with
      pentobarbital sodium. The intracavernous pressure (ICP) was used as an
      experimental index for penile erection, and was recorded alongside systemic
      arterial pressure and heart rate. The effect on ICP of electrical (30-s train of
      30-120 microA, 40-160 Hz, 1-ms rectangular pulses) or chemical (L-glutamate, 0.5
      nmol/50 nl.) activation of the paraventricular nucleus of hypothalamus (PVN) or
      hippocampal formation was evaluated. RESULTS: Electrical activation of the PVN
      elicited both multiple and single episodes of elevation in ICP, along with
      visible erection and ejaculation. The former pattern exhibited an increase in ICP
      that was more sustained, with higher peak amplitude and longer latency. Chemical
      stimulation of neuronal perikarya in the PVN also resulted in similar patterns of
      rise in ICP and visible erection. These effects were, nonetheless, not
      accompanied by significant alterations in systemic arterial pressure and heart
      rate. Activation of the hippocampal formation, as we reported previously,
      similarly elicited multiple and single episodes of increase in ICP. These
      erectile responses, however, were substantially reduced or eliminated upon
      electrolytic lesion of the ipsilateral PVN. CONCLUSION: These observations
      suggest that the PVN may be an important nucleus that participates in central
      neural regulation of penile erection in the rat. Furthermore, an efferent
      pathway(s) from the hippocampal formation to PVN may constitute part of the
      neural circuitry in the forebrain in the regulation of erectile functions.

PMID- 9186368
TI  - Retrospective evaluation of c-erbB-2 oncogene amplification using competitive PCR
      in collecting duct carcinoma of the kidney.
AB  - PURPOSE: To evaluate retrospectively c-erbB-2 oncogene amplification in paraffin
      embedded specimens of collecting duct carcinoma of the kidney (CDC) with
      competitive polymerase chain reaction (PCR). MATERIALS AND METHODS: Eleven CDC
      specimens were evaluated with a novel PCR procedure for oncogene amplification
      measurement, which provides sensitive and accurate results even in presence of
      low-quality DNA, unsuitable for Southern blot techniques. RESULTS: c-erbB-2
      oncogene amplification was present in 5 out of 11 cases (45%) with a number of
      copies ranging from 4 to 12. All patients presenting oncogene amplification
      decreased within one year, while 50% (3/6) of those without amplification are
      alive with a mean follow-up of 42 months. CONCLUSIONS: The high incidence of c
      erbB-2 oncogene amplification in CDC further characterizes this tumor as a
      separate entity from renal cell carcinoma, and shows some genetic characteristics
      in common with transitional cell carcinoma.

PMID- 9186369
TI  - Evidence for altered proliferative ability of progenitors of urothelial cells in
      interstitial cystitis.
AB  - Secondary cultures of basal urothelial cells isolated from patients with stress
      incontinence (7 patients), neurogenic bladder (2 patients), interstitial cystitis
      (IC) (27 patients), bladder rupture (1 patient) and bacterial cystitis (3
      patients) grew under growth restricting conditions. All groups displayed
      reproducible colony size distribution, reflecting the proliferative potential
      distribution in the population of progenitor cells seeded. The percentage of
      large colonies (> 6 cells/colony), progeny of basal cells with high proliferative
      potential, was low in cultures from control patients with stress incontinence,
      neurogenic bladder or bladder rupture. Exposure of cultures from control patients
      with stress incontinence to lipoteichoic acid from Streptococcus faecalis, in
      vitro, increased the percentage of large colonies to levels statistically
      indistinguishable from those in untreated IC cultures. This supported the
      possibility that exposure of progenitors of urothelial cells to infection in vivo
      may cause the persistent increase in the percentage of large colonies in 80% of
      the IC patients tested. Given these findings, it was not surprising that the
      percentage of large colonies was also high in cultures from patients with acute
      bacterial cystitis. In conclusion, the present findings support the theoretical
      model for the etiology of IC we proposed based on our studies in normal
      urothelial cells (Elgavish et al., Journal of Cellular Physiology 169: 42-51, 52
      65, 66-77, 1996): (1) The proliferative ability of a subpopulation of progenitors
      of urothelial cells is increased in IC; and (2) This change may be the result of
      recurrent exposure of progenitors of urothelial cells to injury due, possibly but
      not exclusively, to infection and chronic inflammation. We propose to use this
      change as a diagnostic tool for IC.

PMID- 9186370
TI  - Evaluation of the effect of endothelin-1 and characterization of the selective
      endothelin a receptor antagonist PD155080 in the prostate.
AB  - PURPOSE: To evaluate the contractile effect of endothelin-1 (ET-1) on prostatic
      urethral pressure and to characterize the effect of the selective ETA receptor
      antagonist PD155080 on ET-1 mediated prostatic urethral pressure. MATERIALS AND
      METHODS: The effect of intravenous ET-1 administration on canine urethral
      pressure was determined in the presence and absence of PD155080. The affinity of
      PD155080 for endothelin-mediated contraction was determined using antagonist
      dissociation studies. Saturation and competition binding studies were performed
      using [125I] ET-1 in both human and canine prostate. RESULTS: ET-1 bolus
      injection elicited shallow and prolonged increases the prostatic urethral
      pressure. Pretreatment with PD155080 totally abolished the urethral contractile
      response to ET-1. Specific [125I] ET-1 binding was saturable and of high
      affinity. Two ET receptor subtypes (ETA receptor, ETB receptor) have been
      identified in human prostate. The ratio of ETA to ETB receptors was approximately
      1.5:1 in both human and canine prostates. Isometric tension studies revealed that
      PD155080 shifted the ET-1 dose-response curves to the right and exhibited no
      effect on the ETB receptor selective agonist sarafotoxin dose-response curves.
      CONCLUSION: ET-1 mediates prostate smooth muscle tone and may play a role in the
      pathophysiology and treatment of benign prostatic hyperplasia (BPH).

PMID- 9186371
TI  - Effect of octreotide, a somatostatin analogue, on release of inflammatory
      mediators from isolated guinea pig bladder.
AB  - OBJECTIVE: Somatostatin has been demonstrated to inhibit inflammation under
      certain circumstances. We hypothesized that in vivo treatment with octreotide, a
      long-acting analogue of somatostatin analogue, would diminish the capacity of
      inflammatory peptides to stimulate in vitro release of inflammatory mediators by
      the bladder. METHODS: Female guinea pigs were injected with octreotide (20
      mg./kg. i.m.) prior to euthanasia. Control guinea pigs received no treatment
      prior to euthanasia. Urinary bladders were removed and incubated with substance P
      (SP, 10 microM), neurokinin A (NKA, 10 microM), or bradykinin (BK, 10 microM) in
      the presence or absence of indomethacin (50 microM), and release of histamine,
      prostaglandins (PGE2 and PGF2 alpha), and leukotriene (LTB4) was determined.
      RESULTS: Sensory peptides and BK induced time-dependent release of histamine and
      eicosanoids from isolated urinary bladder. Blockade of cyclooxygenase with
      indomethacin (50 microM) abolished peptide-induced prostaglandin release but
      enhanced LTB4 release. In vivo octreotide pretreatment decreased peptide-induced
      histamine release, had no effect on PGE2 or PGF2 alpha release, and LTB4 release.
      However, octreotide prevented the increase in LTB4 release in tissues incubated
      with indomethacin. CONCLUSIONS: These results indicate that somatostatin has the
      capacity to suppress the release of histamine and prevents potentiation of LTB4
      release by indomethacin by the guinea pig bladder in response to pro-inflammatory
      peptides, indicating that somatostatin may be useful in preventing or treating
      some forms of cystitis.

PMID- 9186372
TI  - Increased cell proliferation of urothelium in rat bladder following unilateral
      nephrectomy.
AB  - PURPOSE: The aim of this study is to investigate the effect of unilateral
      nephrectomy on cell proliferation of normal urinary bladder epithelium in adult
      rats. MATERIALS AND METHODS: Following unilateral nephrectomy or sham operation 5
      rats for each time point were sacrificed and their bladders were removed at 6 and
      12 hours and also on 1, 2, 4, 7, 14, 28, and 56 days. Another 5 rats were not
      operated and served as the control. The percent number of proliferating cell
      nuclear antigen (PCNA) positive cells and the number of argyrophilic nucleolar
      organizer regions (AgNORs) were determined for each bladder. RESULTS: In the
      nephrectomized groups, a significant increase of PCNA expression in urothelial
      cells of the bladder was found at each sacrifice time with the exception of 28
      and 56 days when compared with that of the control and corresponding sham
      operated groups. Percent PCNA labeling index (PCNA-LI) reached a peak value of
      approximately 9.1% on day 2 post operation. From day 4 post nephrectomy, however,
      PCNA-LI decreased gradually reaching control levels by day 28. No significant
      difference was found between the control and sham-operated groups. The mean
      number of AgNOR dots in nephrectomized rats sacrificed on day 1, 2, 4, 7 and 14
      post operation was significantly larger than that of the control and
      corresponding sham-operated groups. CONCLUSION: The results suggest that
      unilateral nephrectomy temporarily enhances normal urothelial cell proliferation
      in adult rat bladder.

PMID- 9186373
TI  - Protein kinase C mediated anti-proliferative glucocorticoid-sphinganine synergism
      in cultured Pollard III prostate tumor cells.
AB  - PURPOSE: Experimental effort focused on the growth inhibition of an androgen
      resistant prostatic carcinoma, using pharmacological inhibition of protein kinase
      C (PKC) as the therapeutic target. MATERIALS AND METHODS: Studies were performed
      in cell culture using the Pollard (PA) III androgen-insensitive spontaneous rat
      prostate tumor cells, and the human prostate tumor lines, PC-3 and LnCaP.
      Pharmacological agents included steroid hormones and PKC modulators; measured
      parameters of tumor growth/function included cell number, PKC activity and
      sphingolipid metabolism. RESULTS: Triamcinolone (TA) and sphinganine synergized
      to inhibit the proliferation rate of PA III prostate tumor cells by converging
      through separate mechanisms to inhibit protein kinase C. At five days of cell
      culture, 0.1 microM TA reduced both the soluble and particulate forms of PKC in
      association with a 35-40% reduction in cellular proliferation. Exogenous
      sphinganine, a competitive inhibitor at the regulatory domain of PKC had no anti
      proliferative effect at 1 microM, but in combination with TA synergized to reduce
      proliferation 80-90%, three days in advance of any detectable inhibitory effect
      of TA alone on cell number. TA produced no discernable stimulation of endogenous
      free sphingosine production as evidenced by the lack of an effect on the activity
      of neutral membrane sphingomyelinase or in the turnover of total cellular
      sphingomyelin. Phorbol esters, but not cell permeable diglycerides, prevented the
      TA + sphinganine effect suggesting that a stable long term PKC activation was
      required for reversal. Steroid specificity studies of the synergistic response
      revealed that while other glucocorticoids mimicked TA, aldosterone was less
      active and representatives of the three major classes of sex steroids were inert.
      Tests of sphinganine specificity demonstrated that calphostin C, a chemically
      unrelated inhibitor of the regulatory site of PKC, also produced a supra-additive
      interaction with TA. Ceramides (C2 & C6), which were closely related chemically
      to sphinganine but lacked affinity for the regulatory subunit of PKC, were
      inactive in this system. Analyses of the cellular specificity of the TA
      sphinganine synergism using the human prostate carcinoma cell lines PC-3 and
      LnCap revealed a true synergistic growth inhibition in the glucocorticoid
      receptor positive PC-3 line and no significant interaction in the glucocorticoid
      receptor negative LnCap cells. CONCLUSIONS: TA-induced reduction of PKC
      concentration coupled with sphinganine antagonism of PKC activation contributed
      to in a synergistic growth inhibition of an androgen resistant prostatic
      carcinoma.

PMID- 9186375
TI  - Good manners for the pharmaceutical industry.

PMID- 9186374
TI  - Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in
      chemically induced rat renal carcinoma cell.
AB  - PURPOSE: von Hippel-Lindau (VHL) gene mutations are detected in noninherited,
      sporadic human renal cell carcinomas (RCs) at a high frequency. We recently
      identified a germline mutation in the rat homologue of the human tuberous
      sclerosis (TSC2) predisposing RC gene in the Eker rat model, and in this study we
      searched for mutations of the Tsc2 gene in chemically induced non-Eker rat RCs.
      MATERIALS AND METHODS: Chemically [N-ethyl-N-hydroxyethylnitrosamine (EHEN)]
      induced non-Eker rat RC lines (designated as BP13 and BP36B) were subjected to
      PCR-single strand conformation polymorphism (PCR-SSCP) analysis using specific
      primers covering entire exons of Tsc2 gene (41 coding exons and one non-coding
      exon). We simultaneously searched for mutations of Vhl gene, a rat homologue of
      von Hippel-Lindau disease gene (VHL) as well as Tsc2 gene. RESULTS: BP36B showed
      an abnormal mobility shift from the normal tissue of the same rat in exon 35 on
      analysis by PCR-SSCP. This mutation was confirmed by direct sequencing and found
      to be a T-to-C transition at the second position of codon 1470, resulting in an
      amino acid change from leucine to proline (missense mutation). CONCLUSIONS: This
      is the first demonstration of Tsc2 gene somatic mutation in non-Eker rat RCs. Our
      present findings call attention to further investigation of the role of Tsc2 gene
      mutations in rat renal carcinogenesis and possible Tsc2 gene mutations in human
      RCs, especially of the non-clear cell type, which are not related to the VHL
      gene.

PMID- 9186376
TI  - Nature's experiment: what implications for malaria prevention?

PMID- 9186377
TI  - Proton-pump inhibitors: three of a kind?

PMID- 9186378
TI  - Ventilation in the prone position.

PMID- 9186379
TI  - For WHO or for whom?

PMID- 9186380
TI  - Late but warranted pardons.

PMID- 9186381
TI  - CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients
      with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative
      Group.
AB  - BACKGROUND: Aspirin is effective in the treatment of acute myocardial infarction
      and in the long-term prevention of serious vascular events in survivors of stroke
      and myocardial infarction. There is, however, no reliable evidence on the
      effectiveness of early aspirin use in acute ischaemic stroke. METHODS: The
      Chinese Acute Stroke Trial (CAST) was a large randomised, placebo-controlled
      trial of the effects in hospital of aspirin treatment (160 mg/day) started within
      48 h of the onset of suspected acute ischaemic stroke and continued in hospital
      for up to 4 weeks. The primary endpoints were death from any cause during the 4
      week treatment period and death or dependence at discharge, and the analyses were
      by intention to treat. 21,106 patients with acute ischaemic stroke were enrolled
      in 413 Chinese hospitals at a mean of 25 h after the onset of symptoms (10,554
      aspirin, 10,552 placebo). 87% had a CT scan before randomisation. It was
      prospectively planned that the results would be analysed in parallel with those
      of the concurrent. International Stroke Trial (IST) of 20,000 patients with acute
      stroke from other countries. FINDINGS: There was a significant 14% (SD 7)
      proportional reduction in mortality during the scheduled treatment period (343
      [3.3%] deaths among aspirin-allocated patients vs 398 [3.9%] deaths among placebo
      allocated patients; 2p = 0.04). There were significantly fewer recurrent
      ischaemic strokes in the aspirin-allocated than in the placebo-allocated group
      (167 [1.6%] vs 215 [2.1%]; 2p = 0.01) but slightly more haemorrhagic strokes (115
      [1.1%] vs 93 [0.9%]; 2p > 0.1). For the combined in-hospital endpoint of death or
      non-fatal stroke at 4 weeks, there was a 12% (6) proportional risk reduction with
      aspirin (545 [5.3%] vs 614 [5.9%]; 2p = 0.03), an absolute difference of 6.8
      (3.2) fewer cases per 1000. At discharge, 3153 (30.5%) aspirin-allocated patients
      and 3266 (31.6%) placebo-allocated patients were dead or dependent, corresponding
      to 11.4 (6.4) fewer per 1000 in favour of aspirin (2p = 0.08). INTERPRETATION:
      There are two major trials of aspirin in acute ischaemic stroke. Taken together,
      CAST and the similarly large IST show reliably that aspirin started early in
      hospital produces a small but definite net benefit, with about 9 (SD 3) fewer
      deaths or non-fatal strokes per 1000 in the first few weeks (2p = 0.001), and
      with 13 (5) fewer dead or dependent per 1000 after some weeks or months of follow
      up (2p < 0.01).

PMID- 9186382
TI  - Relation between severe malaria morbidity in children and level of Plasmodium
      falciparum transmission in Africa.
AB  - BACKGROUND: Malaria remains a major cause of mortality and morbidity in Africa.
      Many approaches to malaria control involve reducing the chances of infection but
      little is known of the relations between parasite exposure and the development of
      effective clinical immunity so the long-term effect of such approaches to control
      on the pattern and frequency of malaria cannot be predicted. METHODS: We have
      prospectively recorded paediatric admissions with severe malaria over three to
      five years from five discrete communities in The Gambia and Kenya. Demographic
      analysis of the communities exposed to disease risk allowed the estimation of age
      specific rates for severe malaria. Within each community the exposure to
      Plasmodium falciparum infection was determined through repeated parasitological
      and serological surveys among children and infants. We used acute respiratory
      tract infections (ARI) as a comparison. FINDINGS: 3556 malaria admissions were
      recorded for the five sites. Marked differences were observed in age, clinical
      spectrum and rates of severe malaria between the five sites. Paradoxically, the
      risks of severe disease in childhood were lowest among populations with the
      highest transmission intensities, and the highest disease risks were observed
      among populations exposed to low-to-moderate intensities of transmission. For
      severe malaria, for example, admission rates (per 1000 per year) for children up
      to their 10th birthday were estimated as 3.9, 25.8, 25.9, 16.7, and 18.0 in the
      five communities; the forces of infection estimated for those communities (new
      infections per infant per month) were 0.001, 0.034, 0.050, 0.093, and 0.176,
      respectively. Similar trends were noted for cerebral malaria and for severe
      malaria anaemia but not for ARI. Mean age of disease decreased with increasing
      transmission intensity. INTERPRETATION: We propose that a critical determinant of
      life-time disease risk is the ability to develop clinical immunity early in life
      during a period when other protective mechanisms may operate. In highly endemic
      areas measures which reduce parasite transmission, and thus immunity, may lead to
      a change in both the clinical spectrum of severe disease and the overall burden
      of severe malaria morbidity.

PMID- 9186383
TI  - Socioeconomic inequalities in morbidity and mortality in western Europe. The EU
      Working Group on Socioeconomic Inequalities in Health.
AB  - BACKGROUND: Previous studies of variation in the magnitude of socioeconomic
      inequalities in health between countries have methodological drawbacks. We tried
      to overcome these difficulties in a large study that compared inequalities in
      morbidity and mortality between different countries in western Europe. METHODS:
      Data on four indicators of self-reported morbidity by level of education,
      occupational class, and/or level of income were obtained for 11 countries, and
      years ranging from 1985 to 1992. Data on total mortality by level of education
      and/or occupational class were obtained for nine countries for about 1980 to
      about 1990. We calculated odds ratios or rate ratios to compare a broad lower
      with a broad upper socioeconomic group. We also calculated an absolute measure
      for inequalities in mortality, a risk difference, which takes into account
      differences between countries in average rates of illhealth. FINDINGS:
      Inequalities in health were found in all countries. Odds ratios for morbidity
      ranged between about 1.5 and 2.5, and rate ratios for mortality between about 1.3
      and 1.7. For men's perceived general health, for instance, inequalities by level
      of education in Norway were larger than in Switzerland or Spain (odds ratios [95%
      CI]: 2.57 [2.07-3.18], 1.60 [1.30-1.96], 1.65 [1.44-1.88], respectively). For
      mortality by occupational class, in men aged 30-44, the rate ratio was highest in
      Finland (1.76 [1.69-1.83]), although there was no large difference in the size of
      the inequality in those countries with data. For men aged 45-59, for whom France
      did have data, this country had the largest inequality (1.71 [1.66-1.77]). In the
      age-group 45-64, the absolute risk difference ranked Finland second after France
      (9.8% [9.1-10.4], 11.5% [10.7-12.4]), with Sweden and Norway coming out more
      favourably than on the basis of rate ratios. In a scatter-plot of average rank
      scores for morbidity versus mortality. Sweden and Norway had larger relative
      inequalities in health than most other countries for both measures; France fared
      badly for mortality but was average for morbidity. INTERPRETATION: Our results
      challenge conventional views on the between-country pattern of inequalities in
      health in western European countries.

PMID- 9186384
TI  - Acute and chronic diarrhoea and abdominal colic associated with enteroaggregative
      Escherichia coli in young children living in western Europe.
AB  - BACKGROUND: Enteroaggregative Escherichia coli (EAggEC or EAEC) can spread and
      cause disease in developing countries, but it is not presently known whether it
      spreads disease in industrialised countries. Therefore, we did a prospective
      study to assess the incidence and the clinical manifestations of infections due
      to EAEC in children in Germany. METHODS: 798 children with diarrhoea, admitted to
      hospital within a defined geographical area during a 24-month period, were
      included in the trial. EAEC were cultured from stool specimens, screened by PCR,
      and identified by colony hybridisation from DNA sequences found on the virulence
      plasmid. The findings were confirmed by aggregative adherence to HEp-2 cells.
      Stool samples from 580 children admitted to hospital without diarrhoea were also
      studied as controls. FINDINGS: EAEC were found in the stools of 16 (2%) of 798
      children with diarrhoea, but in none of 580 children without diarrhoea. Only four
      of the EAEC-infected children had travelled to developing countries. Most EAEC
      infections were acquired in the summer months. Infection with EAEC was associated
      with acute, watery diarrhoea in 12 children, and with chronic diarrhoea of up to
      5 months' duration in four. Five children had abdominal colic that lasted for 2-4
      weeks as their main symptom. The incidence of EAEC infection was 7.7 patients
      admitted to hospital per 100,000 children in the general population aged younger
      than 16 years. INTERPRETATION: EAEC infection is associated with acute, watery
      diarrhoea and may be acquired in industrialised countries. Chronic diarrhoea or
      abdominal colic of unknown aetiology in young children may also be caused by EAEC
      infection.

PMID- 9186385
TI  - Randomised feasibility trial of pre-exposure rabies vaccination with DTP-IPV in
      infants.
AB  - BACKGROUND: Pre-exposure vaccination against rabies generally simplifies
      treatment and could be especially beneficial to children in countries where the
      disease is enzootic. We studied the feasibility of administering to infants pre
      exposure rabies vaccination with combined diphtheria, tetanus, whole-cell
      pertussis, and inactivated poliomyelitis vaccine (DTP-IPV). METHODS: 84
      Vietnamese infants were randomly assigned to groups that received three doses of
      DTP-IPV vaccine at 2, 3, and 4 months of age alone (n = 43) or with two doses of
      purified Vero cell rabies vaccine (PVRV) at 2 and 4 months (n = 41). The safety
      and immunogenicity data of the groups were compared. FINDINGS: All infants in
      both groups developed protective antibody concentrations against diphtheria,
      tetanus, pertussis, and polio. All infants who received the PVRV vaccine
      developed protective antibody concentrations against rabies. No serious adverse
      effects were reported, nor did systemic reactions differ between groups.
      INTERPRETATION: Administration of PVRV with DTP-IPV proved safe, and elicited
      what are presumed to be protective antibody concentrations to all antigens in all
      41 infants. Confirmation of these results could lead to integration of pre
      exposure rabies vaccination into Expanded Programme on Immunisation (EPI)
      sessions in selected countries where rabies is enzootic.

PMID- 9186386
TI  - A 9-year-old with fever and severe muscle pains.

PMID- 9186387
TI  - Percutaneous mitral valvotomy with a metal dilatator.

PMID- 9186388
TI  - Reduction of Lyme disease exposure by recognition and avoidance of high-risk
      areas.

PMID- 9186389
TI  - Intradermal blue dye to identify sentinel lymph-node in breast cancer.

PMID- 9186390
TI  - Mannose-binding lectin alleles in a prospectively recruited UK population. The
      ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

PMID- 9186391
TI  - Enterohaemorrhagic Escherichia coli in Central African Republic.

PMID- 9186392
TI  - Insect repellents and the efficacy of sunscreens.

PMID- 9186393
TI  - Adverse event with first-dose perindopril in congestive heart failure.

PMID- 9186394
TI  - Conus geographus envenomation.

PMID- 9186395
TI  - Prostate cancer diagnosis and management.

PMID- 9186396
TI  - Genetic haemochromatosis. Report of a meeting of physicians and scientists at the
      Royal Free Hospital School of Medicine.

PMID- 9186397
TI  - What, if any, is the effect of malnutrition on immunological competence?

PMID- 9186398
TI  - Oral versus intravenous corticosteroids in acute relapses of multiple sclerosis.

PMID- 9186399
TI  - Oral versus intravenous corticosteroids in acute relapses of multiple sclerosis.

PMID- 9186400
TI  - Oral versus intravenous corticosteroids in acute relapses of multiple sclerosis.

PMID- 9186401
TI  - Oral versus intravenous corticosteroids in acute relapses of multiple sclerosis.

PMID- 9186402
TI  - Coeliac disease and insulin-dependent diabetes mellitus.

PMID- 9186403
TI  - Deaths after ivermectin treatment.

PMID- 9186404
TI  - A world free from polio?

PMID- 9186405
TI  - Abdominal aortic aneurysm.

PMID- 9186406
TI  - Central venous line and neurological deficit.

PMID- 9186407
TI  - Calcium-channel blockers and risk of cancer.

PMID- 9186408
TI  - Rheumatic heart disease in developing countries.

PMID- 9186409
TI  - Repetitive strain injuries.

PMID- 9186410
TI  - Repetitive strain injuries.

PMID- 9186411
TI  - Repetitive strain injuries.

PMID- 9186412
TI  - Nutritional replenishment as an alternative to TNF-alpha in Crohn's disease.

PMID- 9186413
TI  - Infection and childhood leukaemia near nuclear sites.

PMID- 9186414
TI  - Conflict of interest in clinical research: opprobium or obsession?

PMID- 9186415
TI  - Informed consent in clinical research: the crisis in paediatrics.

PMID- 9186416
TI  - Access to antiviral therapies in African countries.

PMID- 9186417
TI  - Chopping of hands.

PMID- 9186418
TI  - Reporting of nvCJD cases in lay press.

PMID- 9186420
TI  - Reduction of IOP with latanoprost.

PMID- 9186421
TI  - Repair of rhegmatogenous retinal detachments.

PMID- 9186422
TI  - Postoperative irradiation.

PMID- 9186423
TI  - Irreversible silicone oil adhesion.

PMID- 9186424
TI  - AMD after ECCE with IOL implant.

PMID- 9186425
TI  - Antibiotic supplementation of intraocular irrigating solutions.

PMID- 9186426
TI  - Reversal of iatrogenic punctal and canalicular occlusion.

PMID- 9186427
TI  - Orbital venous anomalies. A long-standing dilemma.

PMID- 9186428
TI  - Orbital venous anomalies.
AB  - PURPOSE: The purpose of the study is to establish the natural history, probable
      nature, and optimal treatment of lesions within the orbit described previously as
      lymphangiomas or orbital varices. METHODS: The clinical and radiologic records of
      158 patients with these lesions were reviewed. Of these, 91 had surgery, and
      histologic specimens from 57 were re-examined. RESULTS: Most patients were
      infants or children with a dark blue swelling in the superomedial part of the
      orbit, orbital hemorrhage, or proptosis. Computed tomography showed smooth,
      contoured lesions denser than brain extending posteriorly. Half enlarged with the
      Valsalva maneuver, 31% contained phleboliths. Surgery was performed in 91
      patients, mainly for cosmesis. Excised tissue included endothelium-lined channels
      containing blood in the orbit and clear fluid in many superficial specimens.
      CONCLUSIONS: The behavior of these lesions and their prevalence in infancy and
      childhood favor a hamartoma. The authors observed a seamless range of clinical
      features that they could not subdivide, particularly in relation to any
      connection with the orbital veins. Many bleed and enlarge permanently and need
      excision, but surgery is difficult and management should be as conservative as
      possible. The origin of these lesions cannot be determined by histopathologic
      analysis, although the authors have evidence of venous features in the orbit and
      lymphatic features more superficially. The authors' clinical findings support a
      venous origin. Two-thirds have either a free venous connection or phleboliths.
      Their distribution corresponds with that of the normal orbital veins, and at
      surgery they derive from or replace those veins. "Orbital venous anomaly" is the
      most accurate term for their description.

PMID- 9186429
TI  - The prevalence and implications of ocular hypertension and glaucoma in thyroid
      associated orbitopathy.
AB  - PURPOSE: The authors determined the prevalence of ocular hypertension and its
      association with progression to glaucomatous damage in patients with thyroid
      associated orbitopathy (TAO). METHODS: The charts of 500 consecutive patients
      with TAO seen at the Allegheny General Hospital (Pittsburgh, PA) between 1985 and
      1995 were analyzed. The amount of proptosis, degree and duration of myopathy,
      exposure to corticosteroids, prior glaucoma treatment, and family history of
      glaucoma were evaluated. RESULTS: One hundred twenty (24%) patients with TAO were
      noted to have an intraocular pressure (IOP) greater than 22 mmHg but less than 30
      mmHg. This ocular hypertensive group was composed of 34 men and 86 women with a
      mean age of 55 years and mean follow-up of 4 years. Seven patients were defined
      as glaucoma suspects, based on increased but nonprogressive cup-to-disc ratios or
      nonprogressive, atypical visual field changes in the presence of increased IOP.
      Two patients demonstrated progressive visual field abnormalities and cupping. Of
      the factors evaluated, only the duration of active orbital involvement was
      statistically associated with progression to glaucomatous damage. The mean
      duration of TAO was 3, 8, and 12 years for ocular hypertensives, glaucoma
      suspects, and glaucomatous damage, respectively. CONCLUSIONS: Only a prolonged
      duration of active TAO in association with ocular hypertension correlated with
      progression to glaucomatous damage. These patients with chronic TAO deserve
      special attention and close follow-up to prevent optic nerve damage.

PMID- 9186430
TI  - Congenital periodic alternating nystagmus. Diagnosis and Management.
AB  - PURPOSE: The purpose of the study is to investigate diagnostic criteria and
      treatment methods for patients with congenital periodic alternating nystagmus
      (PAN). METHODS: A retrospective analysis was performed of clinical findings and
      serial eye movement recordings of patients with congenital PAN. Eighteen patients
      observed from 1983 through 1996 and diagnosed with congenital PAN are included.
      Five of these have ocular or oculocutaneous albinism. Nine of the 18 patients
      were treated. Three had Kestenbaum operations before referral to the authors, one
      was treated with baclofen, and five had large recessions of the four horizontal
      recti. The studied parameters included visual acuity (VA) and abnormal head
      posture (AHP); temporal aspects of PAN cycle, nystagmus waveforms, frequency,
      amplitude, and velocity; as well as mean foveation fraction, a mean percentage of
      the nystagmus cycle spent at retinal slip velocities less than 10 degrees per
      second. RESULTS: The authors diagnosed PAN in 9% of patients with congenital
      nystagmus, although most had not been diagnosed with PAN before referral, despite
      changing nystagmus. Sixteen patients had AHP, typically shifting. The PAN cycle
      was of variable duration, often with asymmetric right- and left-beating
      components. Although horizontal jerk nystagmus with accelerating slow phase was
      predominant, other waveforms were encountered in the active phase of PAN. In the
      quiet phase (close to null zone), similar, but less intense, oscillations than
      those in the active phase were characteristic. Half of the patients showed a
      combination of waveforms in both phases. Baclofen treatment was unsuccessful.
      Patients who had Kestenbaum procedures remained with AHP in the original or
      opposite direction, without change in nystagmus or VA. Large recessions of four
      horizontal recti proved uncomplicated. This treatment improved, at least for
      several years, AHP and VA and caused favorable changes in nystagmus parameters in
      all patients. Mean foveation fractions increased significantly after surgery.
      CONCLUSIONS: Congenital PAN often is underdiagnosed. Differing waveforms may
      indicate PAN. Evaluation of nystagmus, especially before surgery, for at least 3
      minutes, preferably with eye movement recordings, is necessary to diagnose PAN
      and perhaps prevent Kestenbaum procedures, which seem inappropriate. Large
      horizontal recti recessions seem to provide safe and promising treatment.

PMID- 9186431
TI  - Evidence of optic pathway gliomas after previously negative neuroimaging.
AB  - PURPOSE: The authors emphasize the potential for the development of anterior
      visual pathway gliomas, evidenced by computed tomography (CT) or magnetic
      resonance imaging (MRI) scans, in neurofibromatosis type 1 (NF1) patients who
      previously had normal neuroimaging studies. METHODS: The clinic charts and CT and
      MRI scans were retrospectively reviewed for all patients evaluated at the
      neurofibromatosis clinic of one referral center over a period of 7 years.
      Patients with neuroimaging studies demonstrating anterior visual pathway gliomas
      who previously had normal scans were identified, and their cases are described in
      detail. A similar, previously reported series, from the pediatric literature, was
      also reviewed. RESULTS: Eight percent (28/360) of patients had CT or MRI scans
      revealing optic gliomas. Two of these patients had normal neuroimaging studies
      previously. CONCLUSION: A negative neuroimaging study in an NF1 patient does not
      exclude the future development of an optic glioma.

PMID- 9186432
TI  - Minocycline-induced scleral pigmentation.
AB  - PURPOSE: Minocycline is a commonly used drug in the management of acne and
      rosacea. Four individual cases of oral minocycline-induced scleral pigmentation
      are reported in the dermatologic literature. This is the first report in the
      ophthalmic literature and will add three new cases of probable minocycline
      induced scleral pigmentation. MATERIALS AND METHODS: Data on minocycline from the
      spontaneous reporting systems of the National Registry of Drug-Induced Ocular
      Side Effects, Food and Drug Administration, World Health Organization, and
      Lederle Laboratories were reviewed as to minocycline-related scleral
      pigmentation. Photographs, published cases, discussions with the examining
      ophthalmologists, and the personal observation of one patient (case 1) are the
      basis of the authors' conclusions. RESULTS: Seven cases of probable oral
      minocycline-induced scleral pigmentation are presented. These changes may or may
      not be associated with minocycline-induced pigmentary changes in other tissues,
      such as the skin, teeth, fingernails, bone, thyroid, or mucosa. The
      characteristic scleral pattern is a blue-gray 3- to 5-mm band starting at the
      limbus, which usually is enhanced in the palpebral aperture, possible due to the
      photosensitizing properties of the drug. CONCLUSIONS: Oral minocycline can cause
      scleral pigmentation. This pigmentation may resolve within years, or it may be
      permanent.

PMID- 9186433
TI  - Bilateral iridocyclitis with retinal capillaritis in juveniles.
AB  - PURPOSE: The authors present clinical features of 18 juvenile patients with a new
      type of uveitis termed bilateral iridocyclitis with retinal capillaritis (BIRC).
      METHODS: The authors reviewed medical records of 18 consecutive patients who
      showed bilateral iridocyclitis with retinal capillary leakage but no systemic
      manifestations during an 11-year period from January 1985 to December 1995.
      RESULTS: Twelve of the 18 patients were female and the age at onset ranged from 9
      to 17 years old. All patients had many cells in the anterior chamber and anterior
      vitreous, together with mutton fat keratic precipitates. Fluorescein angiography
      showed leakage from the optic disc and retinal capillaries, mainly in the
      midperiphery, which corresponded to retinal cloudiness. Macular edema was
      minimal, and all patients maintained good vision. The inflammation responded well
      topical, oral, and intravenous administration of corticosteroids, the choice of
      which was based on the extent of retinal inflammation. Human leukocyte antigen
      (HLA)-DR6 and HLA-Cw7 were associated significantly with the presence of BIRC
      (chi square test, P < 0.0001). CONCLUSIONS: Bilateral retinal capillaritis
      affecting capillaries in various areas of the retina and overlying retinal
      cloudiness with no distinct lesions are unique to these patients. Fluorescein
      angiography is essential for diagnosis of BIRC.

PMID- 9186434
TI  - The effect of excimer laser photorefractive keratectomy on intraocular pressure
      measurements using the Goldmann applanation tonometer.
AB  - PURPOSE: The authors determined whether photorefractive keratectomy (PRK) affects
      Goldmann applanation readings in human eyes. METHODS: The intraocular pressure
      (IOP) of 111 patients was measured using Goldmann applanation tonometry at
      baseline and 12 months after PRK. Ultrasonic corneal thickness measurements and
      keratometry were also obtained. Contralateral eyes were used as controls.
      RESULTS: There was a statistically significant decrease in mean tonometer
      readings in the treated eyes when compared with the control eyes (0.5 +/- 2.1
      mmHg, P = 0.01) accompanied by a significant reduction in mean central pachymetry
      in the treated eyes (23 +/- 23 microns, P < 0.001). In the treated eyes, the mean
      spherical equivalent and mean central keratometry readings were significantly
      reduced by 3.3 +/- 1.5 and 2.2 +/- 1.2 diopters, respectively (P < 0.001).
      CONCLUSION: Photorefractive keratectomy causes a mild lowering of the Goldmann
      tonometer readings. The reduction in IOP measurement is probably not enough to
      alter a therapeutic decision in an individual patient known to have glaucoma, but
      it may delay recognition and treatment of glaucoma.

PMID- 9186435
TI  - Analysis of corneal topography after automated lamellar keratoplasty.
AB  - PURPOSE: The purpose of the study is to evaluate the effects of myopic automated
      lamellar keratoplasty (ALK) on corneal topography. METHODS: The authors performed
      a retrospective study of computer-assisted topographic maps obtained before
      surgery and at the last follow-up visit of 9 patients (13 eyes) who underwent ALK
      without enhancement to correct moderate-to-high myopia during a 12-month period.
      RESULTS: Follow-up ranged from 3.5 to 13 months (mean, 5.8; standard deviation,
      3.1). The mean manifest spherical equivalent changed from -10.5 +/- 2.2 diopters
      (D) before surgery to -1.1 +/- 1.8 D at the last follow-up visit. Mean simulated
      keratometry (Sim K) decreased from 45.6 +/- 1.9 D to 38.9 +/- 2.7 D. Mean corneal
      astigmatism increased from 1.3 +/- 0.8 D to 2.1 +/- 0.9 D. The mean surgically
      induced cylinder vector (calculated by vector analysis) was 1.1 +/- 0.6 D. Mean
      surface regularity index (SRI) and surface asymmetry index (SAI) increased from
      0.37 +/- 0.38 and 0.32 +/- 0.43 before surgery to 1.00 +/- 0.32 (P < 0.001) and
      0.75 +/- 0.36 (P = 0.01), respectively, at the last visit. A positive correlation
      was observed between the decrease in mean Sim K and the increase in manifest
      spherical equivalent (reduction of myopia) (r = 0.77, P = 0.002), increase in SRI
      (r = 0.73, P = 0.005), and increase in SAI (r = 0.58, P = 0.04). The change in
      manifest spherical equivalent was significantly less than the change in Slm K (P
      < 0.001). CONCLUSIONS: Myopic ALK significantly flattens the cornea and reduces
      myopia. However, it induces corneal astigmatism and decreases corneal surface
      regularity and symmetry. The degree of myopic correction, as well as the
      surgically induced corneal surface irregularity and asymmetry, is positively
      correlated with the amount of corneal flattering derived from the surgical
      procedure.

PMID- 9186437
TI  - Advancing wave-like epitheliopathy. Clinical features and treatment.
AB  - PURPOSE: The purpose of the study is to describe an entity referred to as
      advancing wave-like epitheliopathy and successful treatment of this keratopathy
      with 1% silver nitrate solution. METHODS: Eleven eyes of 7 patients were
      identified with advancing wave-like epitheliopathy. A thorough history and
      physical examination was performed on each patient, and attempts were made to
      identify the cause for the epitheliopathy. Six eyes with associated visual loss
      due to the epitheliopathy involving the visual axis were treated with 1% silver
      nitrate solution to the superior conjunctival limbus. RESULTS: Possible causes
      for the epitheliopathy included use of antiglaucomatous medications or contact
      lens care solutions (6 of 11 eyes), soft contact lens wear (4 of 11 eyes), a
      history of ocular surgery (3 of 11 eyes), or the presence of an underlying
      dermatologic or inflammatory disorder (3 of 11 eyes). All patients treated with
      1% silver nitrate solution (6 of 6 eyes) experienced resolution of their symptoms
      with either complete or partial resolution of the epitheliopathy. CONCLUSIONS:
      Advancing wave-like epitheliopathy is a keratopathy characterized by
      centripetally advancing waves of coarse, irregular epithelium arising from the
      superior limbus. The cause appears to be multifactorial. Symptoms include ocular
      redness, irritation, and a decrease in visual acuity if the visual axis is
      involved. Application of 1% silver nitrate solution to the superior limbus is
      well tolerated and effective in treating this condition.

PMID- 9186436
TI  - Penetrating keratoplasty in congenital hereditary endothelial dystrophy.
AB  - PURPOSE: The purpose of the study is to determine the outcome of penetrating
      keratoplasty in congenital hereditary endothelial dystrophy. METHODS: Records of
      40 patients (13 males, 27 females) who underwent penetrating keratoplasty (56
      eyes) were reviewed. The mean age at surgery was 11.8 years (range, 2 months-35
      years). The mean follow-up was 37 months (range, 6-136 months). RESULTS: In 35
      (62.5%) of 56 eyes that underwent primary penetrating keratoplasty, the grafts
      survived. Graft survival analysis showed the probability of obtaining a clear
      graft is 92% at 1 year, 72% at 2 years, and 56.5% at 5 years. Graft survival was
      statistically better in eyes where onset of the disease is delayed (P = 0.02), if
      the graft donor age is between 5 and 30 years versus older than 30 years (P =
      0.02), and for patients who kept follow-up appointments versus those who were
      delinquent (P < 0.03). Visual acuity was 20/40 in 1.9%, 20/50 to 20/80 in 18.9%,
      20/100 to 20/300 in 49%, and less than 20/400 in 30.2%. The main causes of graft
      failure were graft rejection (six eyes) and bacterial keratitis (four eyes).
      CONCLUSIONS: Penetrating keratoplasty in congenital hereditary endothelial
      dystrophy is moderately successful, and graft survival is better in cases of
      delayed onset compared with that of congenital onset. Early surgical intervention
      is recommended to prevent development or progression of amblyopia.

PMID- 9186438
TI  - Effects of estrogen use on lens transmittance in postmenopausal women.
AB  - OBJECTIVE: Lens autofluorescence originates from an accumulation of fluorescent
      substances that are associated with the process of cataractogenesis and lens
      aging. The aim of this study was to determine whether postmenopausal estrogen use
      reduces age-related nuclear sclerosis in women. DESIGN: The authors designed a
      case-controlled study. PARTICIPANTS: Nineteen postmenopausal women reporting
      estrogen use for more than 4 years (group 1), 20 postmenopausal women reporting
      no estrogen use (group 2), and 23 age-matched men (group 3) were studied.
      INTERVENTION: The authors performed fluorophotometry. MAIN OUTCOME MEASURES:
      Corneal and lens autofluorescence and lens transmittance were measured. RESULTS:
      Lens transmittance values were 0.905 +/- 0.03, 0.839 +/- 0.08, and 0.841 +/- 0.08
      in the three groups, respectively. There was a statistically significant
      difference between group 1 and the other two groups (P < 0.01). CONCLUSIONS:
      These data are suggestive of a protective effect of estrogen use on the lenses of
      postmenopausal women.

PMID- 9186439
TI  - Comparison of conjunctival autografts, amniotic membrane grafts, and primary
      closure for pterygium excision.
AB  - OBJECTIVE: The purpose of the study is to determine whether amniotic membrane can
      be used as an alternative to conjunctival autograft after pterygium excision.
      DESIGN: A prospective study of amniotic membrane grafts (group A) and primary
      closure (group B) was compared retrospectively with conjunctival autografts
      (group C) in patients with pterygia. PARTICIPANTS: Group A included 46 eyes with
      primary pterygia and 8 eyes with recurrent pterygia, group B had 20 eyes with
      primary pterygia, and group C consisted of 78 eyes with primary and 44 eyes with
      recurrent pterygia. INTERVENTION: For the above three different surgeries, the
      amount of tissue removed was estimated from histopathologic analysis, and the
      result was evaluated by clinical examination. MAIN OUTCOME MEASURES: Recurrence,
      survival analysis, and final appearance were compared. RESULTS: In group A, the
      recurrence rate was 10.9%, 37.5%, and 14.8% for primary, recurrent, and all
      pterygia, respectively (mean follow-up, 11 months). These three rates were
      significantly higher than 2.6%, 9.1%, and 4.9% noted in group C (mean follow-up,
      23 months) (P < 0.001, 0.018, and 0.01, respectively). However, the latter
      recurrence rate was significantly lower than 45% (mean follow-up, 5.2 months) in
      group B for primary pterygia (P < 0.001). The onset of recurrence was delayed
      significantly in group C as compared with that of groups A and B. CONCLUSIONS:
      The relatively low recurrence rate for primary pterygia allows one to use
      amniotic membrane transplantation as an alternative first choice, especially for
      advanced cases with bilateral heads or those who might need glaucoma surgery
      later.

PMID- 9186440
TI  - Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma
      filtering surgery.
AB  - PURPOSE: The differentiating characteristics in blebitis and early and late
      endophthalmitis after glaucoma filtration surgery are reviewed. METHODS: All
      admission records and operative reports, as well as available office notes, on
      patients with blebitis or bleb-associated endophthalmitis admitted to a large
      referral eye center from 1985 to 1995 were reviewed retrospectively. RESULTS: Ten
      cases of blebitis and 33 cases of bleb-associated endophthalmitis were
      identified. One patient with blebitis progressed to culture-positive
      endophthalmitis. Of the 33 cases of bleb-associated endophthalmitis, there were 6
      cases of early endophthalmitis (before postoperative week 6) and 27 cases of late
      endophthalmitis. In early endophthalmitis, Staphylococcus epidermidis was
      isolated on vitreous culture in 4 (67%) of 6 cases, whereas in late
      endophthalmitis, this organism was isolated in only 1 (4%) of 27 cases. In the 27
      late cases, Streptococcus species and gram-negative organisms comprised 48% of
      isolates; of 33 cases of endophthalmitis, 15 (45%) demonstrated no growth on
      vitreous culture. Patients with endophthalmitis fared more poorly than those with
      blebitis in terms of visual outcome. CONCLUSIONS: Because blebitis may be
      prodromal to endophthalmitis, aggressive antimicrobial therapy, perhaps with oral
      quinolones, is warranted. In addition, patients with blebitis should be observed
      closely to identify extension into the vitreous cavity so that intravitreous
      antibiotics can be administered in a timely fashion. Finally, clinicians should
      not extrapolate the results of the Endophthalmitis Vitrectomy Study to the
      postfiltration surgery endophthalmitis given the differing pathogenesis and
      unique spectrum of organisms.

PMID- 9186441
TI  - Mitomycin C-augmented trabeculectomy in refractory congenital glaucoma.
AB  - OBJECTIVE: The purpose of the study is to determine the safety and efficacy of
      mitomycin C-augmented trabeculectomy in children with developmental glaucoma
      treated previously by conventional procedures. DESIGN: Retrospective review of
      all cases of developmental glaucoma with previously failed conventional
      procedures that underwent mitomycin C-augmented trabeculectomy between January
      1992 and December 1994. PARTICIPANTS: A total of 19 eyes of 13 patients were
      included in the study. Nineteen eyes included primary congenital glaucoma (15
      eyes) with documented failure of primary trabeculotomy, Axenfeld-Reiger syndrome
      (2 eyes) and aniridia (2 eyes). INTERVENTION: Mitomycin C-augmented (0.4 mg/ml
      for 3 minutes) trabeculectomy was the chosen intervention. MAIN OUTCOME MEASURES:
      Preoperative and postoperative intraocular pressures (IOPs), visual acuities,
      success rate, bleb characteristics, time of surgical failure, and complications
      were the main outcome measures. RESULTS: The mean IOP was reduced from a
      preoperative level of 33.74 +/- 10.70 mmHg to 11.89 +/- 1.33 mmHg (P < 0.0001)
      with the percentage reduction in IOP being 64.75. The mean follow-up was 19.52 +/
      2.65 months. Visual acuity was maintained in all the cases after surgery.
      Complete success as defined in the authors' study was achieved in 18 eyes
      (94.74%). Only one patient was classified as a qualified success. The bleb was
      characterized by its large elevated, avascular, transparent appearance in all the
      eyes. The only significant complication was retinal detachment in an eye with
      buphthalmos, aphakia, and large axial length. However, the retina was reattached
      successfully by retinal reattachment surgery, and visual acuity improved to the
      preoperative level of 20/200. It was not possible to determine the cause of
      retinal detachment or to assess the possible role of mitomycin C in this
      complication. CONCLUSIONS: Mitomycin C-augmented trabeculectomy is a viable
      option in eyes with failed conventional trabeculotomy surgery.

PMID- 9186442
TI  - Needling revision of glaucoma drainage device filtering blebs.
AB  - PURPOSE: Needling revision is an accepted method of management of poorly
      functioning trabeculectomy blebs. The authors present the outcome of the
      analogous needling revision of poorly functioning filtering blebs over glaucoma
      drainage device (GDD) reservoirs. METHODS: Review of 20 patients (21 eyes) who
      underwent needling to the bleb overlying the GDD reservoir, with or without
      adjunctive 5-fluorouracil injection. RESULTS: In the nine eyes (43%) that were
      considered successes (defined as intraocular pressure [IOP] less than or equal to
      21 mmHg and decrease in IOP greater than or equal to 20% with no additional
      medication or glaucoma surgery), the mean IOP fell from 28.3 +/- 6.4 mmHg to 13.9
      +/- 2.7 mmHg at last follow-up, after a mean of 1.7 needlings (range, 1-3
      needlings) with mean follow-up of 14.6 months (range, 5-35 months [corrected]).
      Needling success was associated with larger GDD surface area (mean, 267 +/- 95
      mm2 vs. 179 +/- 79 mm2 in eyes needled unsuccessfully, P = 0.04) and use of
      Baerveldt implants (six of eight eyes needled successfully). Minor complications
      were few. Endophthalmitis developed in one patient (5% of all eyes) after
      needling. CONCLUSIONS: Needling revision can be useful in the management of
      poorly functioning GDD blebs, although the risk for severe complications exists.

PMID- 9186443
TI  - Long-term effects of tube-shunt procedures on management of refractory childhood
      glaucoma.
AB  - PURPOSE: The authors evaluated the long-term results of tube-shunt surgery in
      management of childhood glaucoma. METHODS: The results of tube-shunt surgery in
      children who had glaucoma refractory to medical or alternative surgical treatment
      in the Glaucoma Service of Wills Eye Hospital during the period 1986 through 1993
      were reviewed. Eighteen eyes of 15 patients were included in the analysis. Follow
      up ranged from 14 to 80 months (mean +/- standard deviation, 47.3 +/- 25.1
      months). RESULTS: In the early postoperative course (6 months after surgery), the
      intraocular pressure (IOP) was between 6 and 21 mmHg in 13 eyes (72.2%) with or
      without glaucoma medication. Two or more years later, IOP was between 6 and 21
      mmHg in four eyes without further glaucoma medication (22.2%) and four eyes
      (22.2%) with the addition of antihypertensive therapy. Five eyes (27.8%) lost
      light perception, whereas seven (38.9%) remained within one line of preoperative
      vision or improved. Twelve eyes underwent 28 additional surgical procedures after
      the tube-shunt operation, mostly to control IOP or manage tube-related
      complications. CONCLUSION: The limited success rate, relatively high complication
      rate, and need for frequent surgical intervention suggest caution regarding the
      prognosis of tube-shunt surgery in children with glaucoma.

PMID- 9186444
TI  - Estimating progression of visual field loss in glaucoma.
AB  - PURPOSE: The authors estimated the prevalence and rates of progressive visual
      field loss in glaucoma patients followed annually for a median of 6.3 years.
      METHODS: Linear regression was used to estimate rates of progression of mean
      deviation, corrected pattern standard deviation (CPSD), clusters of locations
      based on the Glaucoma Hemifield Test (GHT), and location specific changes in C-30
      2 fields of the Humphrey Analyzer. RESULTS: Sixty-seven eyes of 56 patients whose
      first two consecutive fields were abnormal on GHT were included. Almost all
      patients were under treatment or had undergone surgery for glaucoma. Visual field
      deteriorated in 19 (28%) eyes based on worsening of one or more CPSD, GHT
      clusters, or individual test locations (regression slopes significantly different
      from zero). Corrected pattern standard deviation deteriorated in 5 eyes, at least
      one GHT cluster deteriorated in 17 eyes, and one or more individual test
      locations deteriorated in 15 eyes. For those whose visual field deteriorated,
      CPSD increased by 0.9 dB/year. Glaucoma Hemifield Test clusters declined by
      between 1.4 and 2.4 dB/year. Deterioration at individual locations ranged from
      1.0 to 5.0 dB/year. Age, but not baseline visual field severity, was predictive
      of further visual field loss. The odds ratio for the association between
      progressive visual field loss and thinning of the nerve fiber layer was 1.81 (95%
      confidence interval: 0.52, 6.33), and 3.78 (95% confidence interval: 0.80, 18.16)
      for the association between progressive visual field loss and optic disc changes
      during follow-up based on masked photograph readings. CONCLUSIONS: Less than one
      in three eyes of patients with glaucoma had any progressive field loss. Average
      changes in threshold sensitivities of less than 1 dB/year could not be detected
      with seven fields done over 6 years. Larger changes or increased frequency of
      visual field testing would need to occur before smaller changes could be detected
      statistically.

PMID- 9186445
TI  - Association of retinal capillary perfusion with visual status during chronic
      glaucoma therapy.
AB  - PURPOSE: The purpose of the study is to determine whether retinal
      microcirculation is associated with the degree of visual function in glaucomatous
      eyes receiving chronic bilateral medical therapy with topical beta-blockers.
      METHODS: A nonrandomized, 3-year prospective clinical study was undertaken on 37
      patients with glaucoma and normal visual acuity receiving symmetric topical
      medication in both eyes. Humphrey 30-2, Henson CFA 2000, and Vistech 3 and 6
      cycles/degree contrast sensitivity were obtained bilaterally at multiple visits,
      along with Oculix 1000 blue-field estimates of perimacular leukocyte velocity.
      The mean asymmetry of measurements obtained throughout the treatment period for
      each pair of eyes was determined, and correlations were obtained to assess visual
      function asymmetry circulatory asymmetry. RESULTS: Significant associations were
      observed between blue-field entoptic capillary leukocyte velocity measurements
      and those for all three visual function testing methods, the eye with the
      superior vision typically having the higher mean leukocyte velocity (P < 0.001
      for both Humphrey mean deviation and Henson perimetry, P < 0.002 for Humphrey
      corrected pattern standard deviation, and P < 0.02 for contrast sensitivity at
      both 3 and 6 cycles/degree). CONCLUSIONS: Central retinal microcirculation is
      associated with various measures of central and peripheral visual function in
      glaucomatous eyes receiving beta-adrenergic blocker therapy.

PMID- 9186446
TI  - Prevalence and associations of epiretinal membranes. The Blue Mountains Eye
      Study, Australia.
AB  - PURPOSE: The purpose of the study is to determine the prevalence and associations
      of epiretinal membranes in a defined older Australian population and to assess
      their influence on visual acuity. METHODS: Three thousand six hundred fifty-four
      persons 49 years of age or older, representing 88% of permanent residents from an
      area west of Sydney, underwent a detailed eye examination, including stereo
      retinal photography. Epiretinal membranes were diagnosed clinically and from
      photographic grading. RESULTS: Signs of epiretinal membranes were found in 243
      participants (7%; 95% confidence interval [CI], 6.1, 7.6), bilateral in 31%. The
      prevalence was 1.9% in persons younger than 60 years of age, 7.2% in persons 60
      to 69 years of age, 11.6% in persons 70 to 79 years of age, and 9.3% in persons
      80 years of age and older, with slightly higher rates in women. Two stages were
      identified: an early form without retinal folds, termed "cellophane macular
      reflex" present in 4.8%, and a later stage with retinal folds, termed "preretinal
      macular fibrosis" (PMF), found in 2.2% of the population. Preretinal macular
      fibrosis, but not cellophane macular reflex, had a small, significant effect on
      visual acuity. Preretinal macular fibrosis was significantly associated with
      diabetes, after age-gender adjustment, in subjects without signs of diabetic
      retinopathy (odds ratio, 3.2; 95% CI, 1.4, 7.2). Preretinal macular fibrosis also
      was associated with increased fasting plasma glucose (odds ratio, 1.2; 95% CI,
      1.1, 1.3). Epiretinal membranes were found in 16.8% of persons who had undergone
      cataract surgery in one or both eyes (including PMF in 3.7%), in 16.1% of retinal
      vein occlusion cases (PMF in 12.5%), both significantly higher rates than in
      subjects without these conditions (P < 0.0001), and in 11% of persons with
      diabetic retinopathy (PMF in 3.6%), not significantly higher (P = 0.17).
      CONCLUSIONS: This study has documented the frequency and mild effect on vision of
      epiretinal membranes in an older population. Diabetes was associated
      significantly with idiopathic cases, whereas well-known associations with past
      cataract surgery and retinal disease were confirmed.

PMID- 9186447
TI  - Vitreoretinal surgery outcomes. Impact on bilateral visual function.
AB  - PURPOSE: The authors evaluated the impact of vitreoretinal surgery for epiretinal
      membrane (ERM), rhegmatogenous retinal detachment (RRD), and complex retinal
      detachment (CRD) on bilateral visual function. METHODS: Anatomic and visual
      acuity outcomes were reviewed by the authors for all patients who underwent
      surgery for ERM, RRD, or CRD during a 2-year period. Several outcome measures of
      bilateral visual function were applied to quantitate the impact of surgery on
      bilateral visual function. Data were also analyzed by subdividing patients into
      two cohorts based on whether vision in the fellow eye was normal (visual acuity >
      or = 20/40) or abnormal (visual acuity < or = 20/50) at baseline. RESULTS:
      Anatomic and visual acuity outcomes of 187 study eyes were similar to previous
      studies. Postoperatively, the study eye was the eye with better vision in 30.9%,
      26.8%, and 16.7% of patients with ERM, RRD, and CRD, respectively. The mean
      bilateral visual impairment according to American Medical Association Guidelines
      for Disability decreased postoperatively by 8.7% points, 6.8% points, and 3.6%
      points, respectively, and decreased most when vision in the fellow eye was
      abnormal. A higher bilateral visual system functional level resulted
      postoperatively in 10.7% of all patients, including 28.6% of patients with
      abnormal vision in the fellow eye (by definition, the visual system functional
      level of patients with normal vision in the fellow eye could not be improved).
      CONCLUSIONS: Surgery was associated with a reduction in bilateral visual
      disability among patients with ERM, RRD, and CRD, and 28.6% of patients with
      abnormal vision in the fellow eye achieved a higher bilateral visual functional
      level.

PMID- 9186448
TI  - Low-dose intravitreal cidofovir (HPMPC) therapy of cytomegalovirus retinitis in
      patients with acquired immune deficiency syndrome.
AB  - PURPOSE: The authors have shown that long-term treatment of cytomegalovirus (CMV)
      retinitis with 20-microgram intravitreal injections of cidofovir (HPMPC) is
      highly effective but may be associated with iritis and profound hypotony. They
      evaluated the efficacy and safety of 10-microgram intravitreal injections of
      cidofovir and made comparisons with their findings of 20-microgram injections.
      METHODS: The current study was conducted as a nonrandomized consecutive case
      series at the AIDS Ocular Research Unit of the University of California at San
      Diego. Twenty-seven eyes of 18 patients were injected with 10 micrograms
      intravitreal cidofovir and had complete follow-up. These were compared with
      another consecutive series of 24 eyes of 17 patients injected with 20 micrograms
      of cidofovir. MAIN OUTCOME MEASURES: The main outcome in this study was the
      incidence of failure to respond to treatment with 10-microgram injections. The
      authors also compared the time to progression of CMV retinitis after the initial
      intravitreal injections of 10 micrograms and 20 micrograms of cidofovir.
      Secondary outcomes included incidence of iritis and changes in intraocular
      pressure (IOP) after cidofovir injections. RESULTS: The median time to retinitis
      progression was 45 days after a single intravitreal injection of 10 micrograms
      cidofovir compared with 55 days with the authors' series of 20-microgram
      injections. This difference was statistically significant (P = 0.033, log-rank
      test) and appeared to be due principally to a 26% incidence of primary failure in
      the 10-microgram group (progression > or = 750 microns within 28 days, P = 0.0017
      Wilcoxon test). Progression after a second injection of 10 micrograms cidofovir
      was more rapid (32 days, P = 0.037). The incidence of iritis after 10-microgram
      injections was 2.2% compared with 23% with 20-microgram injections (P = 0.003,
      Fisher's exact test, two-tailed). There was less decrease in IOP between the
      baseline injection and subsequent visits in the 10-microgram group. CONCLUSIONS:
      Treatment of CMV retinitis with 10-microgram intravitreal cidofovir injection was
      not as effective as with 20 micrograms and may allow development of drug
      resistance, but there were fewer side effects with the 10-microgram dose. The
      drug appears to have a narrow therapeutic index, and other attempts at reducing
      the side effects while preserving the long-acting effect, such as liposome
      delivery, may be warranted.

PMID- 9186449
TI  - Cardiology in South Africa--where to? Address given at the 20th Biennial Congress
      of the Southern Africa Cardiac Society, October 1996.

PMID- 9186451
TI  - Cardiac disease during pregnancy--a Free State perspective on maternal morbidity
      and mortality.
AB  - AIM: Description of maternal outcome of pregnancies complicated by cardiac
      disease. SETTING: Pelonomi Hospital, Bloemfontein. POPULATION: Black African
      women of low socio-economic background who presented with cardiac disease during
      pregnancy. SAMPLE: All patients who delivered from 1 January 1990 to 1 January
      1995. DESIGN: Descriptive retrospective study. RESULTS: Cardiac disease
      complicated 0.6% of pregnancies. Rheumatic valvular disease dominated in this
      population. The maternal mortality rate was 9.5% while the maternal morbidity
      rate ranged from 50% to 100% for the various lesions. CONCLUSIONS: Cardiac
      disease in pregnancy has high maternal mortality and morbidity rates.
      Hypertension, anticoagulation therapy, late referrals and inadequate counselling
      were important contributing factors. A high priority should be given to
      meticulous contraceptive counselling in patients with cardiac disease.
      Collaboration between obstetricians, physicians and cardiothoracic surgeons in
      imperative.

PMID- 9186450
TI  - Carotid stent-assisted angioplasty.
AB  - We present the results of the first 33 patients who underwent carotid stent
      assisted angioplasty at the Heart Unit of Panorama Medi-Clinic between March 1995
      and June 1996. Intravascular stents (48 Palmaz-Schatz and 1 Wall stent) were
      deployed in the common carotid arteries (5) and internal carotid arteries (38) of
      both symptomatic (28 patients) and asymptomatic patients (5 patients) with > 60%
      stenosis (35 with > 70% and 6 with 60% stenosis). Thirteen patients underwent
      bilateral stent implantation, and had percutaneous transluminal coronary
      angioplasty or a peripheral and/or coronary stent implanted. Mean admission time
      was 2 days. Follow-up for 15 months (mean 9 months) employed clinical evaluation,
      duplex scanning at 6 and 12 months, and cerebral magnetic resonance imaging
      before, 48 hours and 6 months after the procedure. Angiographic success, defined
      as maximal residual stenosis < 10%, was achieved in 100%. Clinical success,
      defined as maximal residual stenosis < 10% and absence of death or recurrent
      transient ischaemic attack or stroke in hospital, was achieved in 97.7% of
      treated lesions. Complications included one procedure-related ipsilateral stroke
      and two angiography-related cerebellar infarcts. No transient ischaemic attacks
      or deaths occurred. No early or late restenoses have been observed to date. This
      experience with carotid stent-assisted angioplasty indicates that interventional
      neurovascular therapies may provide a useful alternative for selected patients
      requiring endoluminal reconstruction of carotid stenoses.

PMID- 9186452
TI  - Isolation of the left subclavian artery in tetralogy of Fallot and bronchial
      anomalies.
AB  - In the normal left-sided aorta, the vertebral arteries arise from the respective
      subclavian arteries. Isolation of the left subclavian artery takes place when the
      distal subclavian artery arises as an extension of a patent ductus arteriosus.
      This report describes a patient with tetralogy of Fallot and a right-sided aortic
      arch with isolation of the left subclavian artery. In addition, the patient also
      has congenital tracheal and bronchial stenosis, with a horseshoe lung.

PMID- 9186453
TI  - Myocardial metabolism--Part I. Round-table discussion.

PMID- 9186454
TI  - Heart failure--perspective on some controversial issues for the clinician. 20th
      Biennial Congress of the Cardiac Society, October 1996.

PMID- 9186456
TI  - South Africans concerned at high cost of medicine.

PMID- 9186455
TI  - New treatment approach for high blood pressure patients defined as
      cardioprotective by physicians.

PMID- 9186458
TI  - Sestamibi versus thallium subtraction scintigraphy in parathyroid localization: a
      prospective comparative study in patients with predominantly mild primary
      hyperparathyroidism.
AB  - BACKGROUND: Technetium 99m sestamibi was recently introduced for the preoperative
      localization of abnormal parathyroid glands in patients with primary
      hyperparathyroidism with promising results. However, the sensitivity of sestamibi
      and thallium to detect abnormal parathyroid glands is partly dependent on the
      gland size. In this study we compared the sensitivity of sestamibi subtraction
      scintigraphy with thallium subtraction scintigraphy in patients with
      predominantly mild increase in serum calcium level. METHODS: Thirty-nine patients
      with primary hyperparathyroidism were included. The mean (+/-SD) serum level of
      calcium was 2.75 +/- 0.17 mmol/L. In 28 (72%) of the patients the serum level of
      calcium was less than 2.85 mmol/L. These patients were classified as having mild
      abnormalities in serum calcium. All patients were investigated before operation
      with both sestamibi and thallium subtraction scintigraphy. RESULTS: In two
      patients autonomous thyroid adenomas precluded subtraction scintigraphy.
      Sestamibi subtraction scintigraphy correctly localized 31 (86%) of 36 parathyroid
      adenomas compared with only 17 (47%) of 36 by thallium subtraction scintigraphy
      (p < 0.001). There was one false-positive result in the sestamibi group because
      of a thyroid adenoma, and two of the scans were negative. Both the sestamibi and
      the thallium subtraction scintigraphy localized one single enlarged gland in all
      three patients with multiple gland involvement. In no case was multiglandular
      disease predicted. CONCLUSIONS: Sestamibi subtraction scintigraphy is superior to
      thallium subtraction scintigraphy and has a high sensitivity to localize a
      solitary parathyroid adenoma in patients with mild increase in serum calcium
      level. The sensitivity decreases in patients with multiglandular parathyroid
      disease and concomitant thyroid nodular abnormalities.

PMID- 9186459
TI  - Octreotide: effective treatment for hyperparathyroidism? A prospective,
      randomized, controlled clinical trial.
AB  - BACKGROUND: Recent studies suggest a role for somatostatin in the medical
      treatment of hyperparathyroidism. In a prospective, randomized, controlled,
      triple blinded clinical trial in patients with primary or secondary
      hyperparathyroidism, we evaluated the response of biochemical parameters relevant
      in hyperparathyroidism to the somatostatin analog octreotide. METHODS: Forty
      patients each with primary or secondary hyperparathyroidism were studied. Among
      other parameters, serum calcium and serum phosphate, parathyroid hormone,
      calcitonin, osteocalcin, and octreotide were assessed before and repeatedly for 4
      hours after a single intravenous application of 200 micrograms octreotide or
      placebo. Subsequent to operation, which was performed on all patients,
      somatostatin-receptor autoradiography of parathyroid tissue was performed.
      RESULTS: After administration of octreotide, which resulted in an increase of
      plasma levels to pharmacologic levels, no significant changes in any of the
      biochemical parameters investigated for were observed. Multivariate analysis did
      not identify patient subpopulations that responded to either drug or placebo (p >
      0.05). Forty-five percent of patients receiving octreotide reported side effects:
      Parathyroid tissue samples of patients with primary or secondary
      hyperparathyroidism were negative for somatostatin-receptor expression.
      CONCLUSIONS: Octreotide has no discernible effect on biochemical parameters of
      patients with primary or secondary hyperparathyroidism. Absence of somatostatin
      receptors, together with lack of octreotide effects, suggests that somatostatin
      is not effective in the medical therapy of hyperparathyroidism.

PMID- 9186460
TI  - Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic
      spread and mode of recurrence.
AB  - BACKGROUND: Nodal status is one of the most important prognostic factors for
      carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of
      recurrence were analyzed by determining the frequency of nodal involvement and
      antemortem and postmortem examination of patients with recurrent disease.
      METHODS: From 1974 to 1994, 36 patients with carcinoma of papilla of Vater
      underwent pancreatectomy at the Kanazawa University Hospital. A precise
      evaluation of the nodal involvement was determined by means of careful pathologic
      review of the extended lymphadenectomy specimen. The mode of recurrence was
      determined by use of autopsy and radiographic examinations. RESULTS: Fifteen
      (42%) of 36 patients had nodal involvement. The lymph nodes with the highest
      metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b)
      and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There
      were no metastases in the perigastric lymph nodes. A significant relationship
      existed between the gross appearance of the primary tumor and nodal involvement
      (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates
      were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The
      5-year survival rates for patients with protruding, mixed type, and ulcerative
      tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were
      significantly correlated to gross appearance and nodal involvement.
      Retroperitoneal recurrence and liver metastasis were main modes of recurrence.
      CONCLUSIONS: Lymph node 13b is important in lymphatic metastasis to the superior
      mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around
      the superior mesenteric artery is needed to improve the prognosis of carcinoma of
      papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving
      pancreatoduodenectomy may be indicated in patients with carcinoma of the papilla
      of Vater.

PMID- 9186461
TI  - Duodenal complications in bladder-drained pancreas transplantation.
AB  - BACKGROUND: The most common type of pancreas transplantation is whole
      pancreaticoduodenal (with bladder drainage) from a cadaver donor. Complications
      can arise not only from the pancreas itself but also from the simultaneously
      transplanted duodenum. The purpose of this study was to analyze the incidence,
      diagnosis, and treatment of duodenal complications and their impact on patient
      and pancreas graft survival rates. METHODS: Our retrospective study is based on
      425 pancreaticoduodenal transplantations performed between July 1, 1986, and June
      30, 1994. Complications pertaining to the duodenal segment were labeled early if
      they occurred within the first postoperative month and late otherwise. Mean
      follow-up was 55 months (range, 13 to 108 months). RESULTS: We noted 85 (20%)
      duodenal complications: duodenal leaks (n = 42), hematuria (n = 26), recurrent
      urinary tract infections (n = 9), duodenal ulceration or necrosis (n = 6), and
      bladder stones (n = 2). Of these complications, 40 (48%) required surgical
      intervention. In all, duodenal complications resulted in 14 (16%) enteric
      conversions and eight (9%) pancreas graft losses (six because of duodenal leak
      and 2 because of hematuria). The mortality rate from duodenal complications was
      0%. CONCLUSIONS: Duodenal complications were common, but they were not associated
      with a high rate of pancreas graft loss (only 9%). With early diagnosis and
      treatment, morbidity can be reduced and death avoided in pancreas transplant
      recipients.

PMID- 9186462
TI  - Hepatic resection for noncolorectal, nonneuroendocrine metastases: a fifteen-year
      experience with ninety-six patients.
AB  - BACKGROUND: The role of liver resection for hepatic metastases from
      noncolorectal, nonneuroendocrine (NCNN) cancers is unknown. This study examines a
      large, single institutional experience of hepatic resection for NCNN metastases.
      METHODS: Records of 96 patients who underwent liver resection for metastatic NCNN
      cancer from 1980 to 1995 at a single institution were reviewed. Survival after
      liver resection in this cohort of patients is reported, and factors predictive of
      survival are analyzed. RESULTS: Resection was performed for liver metastases from
      genitourinary primary tumors (n = 34), soft tissue primary tumors (n = 41), and
      metastases from other primary cancers (n = 21). Extent of liver resection
      included wedge (n = 32), lobectomy (n = 44), and extended hepatic lobectomy (n =
      20). No operative deaths occurred. Overall survival rate after resection at 1, 3,
      and 5 years was 80%, 45% and 37%, respectively (median survival, 32 months), with
      12 actual 5-year survivors. There was no difference in survival according to the
      type of liver resection, bilateral versus unilateral disease, or resection of
      extrahepatic disease. Disease-free interval of less than 36 months before
      discovery of liver metastases, curative resection, and primary tumor group
      (genitourinary was greater than soft tissue, which was greater than
      gastrointestinal) were predictors of a significantly better survival by
      multivariate analysis. CONCLUSIONS: Primary tumor type, disease-free interval,
      and curative resection predict those patients who benefit from hepatic resection.
      Hepatic resection for patients with NCNN metastasis has value in carefully
      selected patients.

PMID- 9186463
TI  - Surgical treatment and outcome for node-negative gastric cancer.
AB  - BACKGROUND: The clinicopathologic characteristics and prognosis for patients with
      node-negative gastric cancer have heretofore remained to be determined. METHODS:
      We analyzed data on 730 of our patients with node-negative gastric cancer who
      underwent curative gastric resection in the Department of Surgery II, Kyushu
      University Hospital, between 1965 and 1990, with reference to prognostic factors.
      The presence of lymph node metastasis was determined by means of routine
      hematoxylin-eosin staining of excised tissues. RESULTS: The 5-year survival rate
      was 91.7% and the 10-year rate was 88.5%; thus the prognosis was good for
      patients with node-negative gastric cancer. When the prognosis was analyzed by
      stratification of each clinicopathologic factor, the survival time was shorter
      for older patients when the size of the tumor was larger, when the tumor involved
      the entire stomach, and when-tissues revealed infiltrative growth, serosal
      invasion, and lymphatic invasion. Extensive lymph node dissection was performed
      for 86.6% of the patients, and for these patients the prognosis was better, with
      a statistical difference. In a multivariate analysis, tumor size, serosal
      invasion, and extensive lymph node dissection proved to be independent prognostic
      factors for patients with node-negative gastric cancer. CONCLUSIONS: Prophylactic
      lymph node dissection for patients with gastric cancer will prolong the survival
      time.

PMID- 9186464
TI  - Eck-Pavlov shunt: the 120th anniversary of the first vascular anastomosis.

PMID- 9186465
TI  - Aortoiliofemoral bypass graft in young adults: long-term results in a series of
      sixty-eight patients.
AB  - BACKGROUND: The aim of this study was to investigate surgical indications and the
      long-term outcomes of aoroiliofemoral reconstructions in adults younger than 45
      years. METHODS: Between 1973 and 1990, 1256 patients underwent infrarenal
      abdominal aortic reconstruction for aortoiliofemoral occlusive disease. Sixty
      eight (5.4%) patients (group 1) were less than 45 years old and form the basis of
      the analysis. They were retrospectively compared with two additional groups of
      patients 45 years and older selected from the entire series. Patients in group 2
      (n = 100) were randomly chosen to determine differences in risk factors,
      associated diseases, operative indications, preoperative findings, and outcomes.
      Patients in group 3 (n = 70) were matched with those in group 1 for gender, risk
      factors, associated diseases, preoperative findings, and operative indications to
      assess the importance of age in determining the short- and long-term outcomes of
      aortoiliofemoral reconstructions. RESULTS: Postoperative mortality rates (1.5%,
      4%, and 4.3% for groups 1, 2, and 3, respectively) and major complication rates
      (4.4%, 7%, and 7.1% for groups 1, 2, and 3, respectively) were comparable among
      the three groups. Ten-year secondary patency rates were 84.6%, 70.6%, and 80.3%,
      for groups 1, 2, and 3, respectively (p = not significant). Ten-year limb salvage
      rates were 86.9%, 78.2%, and 80.6%, for groups 1, 2, and 3, respectively (p = not
      significant). During follow-up a significantly higher percentage of myocardial
      infarction was recorded in group 1 as compared with group 2 (p < 0.03) and group
      3 (p < 0.04). The 10-year survival rate for group 1 was significantly lower than
      that of group 2 (29.0% versus 46.9%; p < 0.005). CONCLUSIONS: Aortoliofemoral
      reconstruction in patients younger than 45 years is a safe procedure with low
      operative risks and good long-term results in patency and limb salvage rates.
      However, life expectancy is poor because of the high incidence of deaths related
      to coronary artery disease.

PMID- 9186466
TI  - Efficacy of cultured epithelial autografts in pediatric burns and reconstructive
      surgery.
AB  - BACKGROUND: Cultured epithelial autografts are regularly used in burn patients,
      but they have not been tested in patients undergoing reconstructive surgery. The
      aim of this study was to analyze and compare the efficacy of cultured grafts in
      both burn and reconstructive surgery patients. METHODS: In six children with
      severe and massive burns, full-thickness areas were grafted with cultured grafts.
      In another six children with hypertrophic or hyperpigmented scars, or both,
      cultured grafts were used to cover defects resulting from scar excision or deep
      dermabrasion. RESULTS: In burn surgery the final cover rate averaged 60% (range,
      0% to 100%). The functional and cosmetic results were good and at least
      equivalent to results after conventional grafting. Fragility, infection, and, in
      particular, mechanical instability of cultured grafts during the first weeks
      after transplantation were the main problems encountered. In reconstructive
      surgery the final cover rate was 100% in all patients. The functional and
      cosmetic results were very good and considered better than those obtained by
      using conventional grafting techniques. No major management problems were
      encountered. CONCLUSIONS: In massively burned children, cultured epithelial
      autografts represent an effective additional and potentially lifesaving method to
      conventional grafting. Questions remain regarding the use of this technique to
      treat less severe burns. For resurfacing-type scar revisions, cultured epithelial
      autografts yield excellent results that appear to be superior to those of
      conventional techniques.

PMID- 9186467
TI  - Changes of adenosine triphosphate-dependent calcium uptake in microsomal
      fractions of rat liver during sepsis.
AB  - BACKGROUND: Intracellular calcium concentration is an important regulator of
      cellular metabolism. Endoplasmic reticulum membranes play an important role in
      the regulation of cytoplasmic calcium in the mammalian liver. The
      characterization of the changes of calcium uptake in endoplasmic reticulum may
      contribute to the potential intracellular mechanisms for cellular dysfunction
      during sepsis. METHODS: The effects of sepsis on the calcium uptake in rough
      endoplasmic reticulum of rat liver were studied. Sepsis was induced by means of
      cecal ligation and puncture (CLP). The control rats underwent sham operation.
      Microsomal fractions were isolated from the liver with differential
      centrifugation. RESULTS: The calcium uptake by liver endoplasmic reticulum was
      decreased by 30% to 35% (p < 0.05) during early sepsis (9 hours after CLP) and by
      38% to 43% (p < 0.05) during late sepsis (18 hours after CLP), respectively. The
      maximum velocity values for adenosine triphosphate (ATP) and for Ca2+ were also
      decreased by 25% to 37% (p < 0.05) during early sepsis and by 35% to 42% (p <
      0.05) during late sepsis. The Michaelis-Menten constant for ATP and Ca2+
      transport had no difference among three groups. The magnesium stimulation and
      vanadate inhibitory activity were also decreased by 17% to 38% (p < 0.05) during
      early sepsis and by 34% to 50% (p < 0.05) during late sepsis. CONCLUSIONS: These
      data demonstrate that ATP-dependent calcium uptake in rough endoplasmic reticulum
      of rat liver was impaired during early and late sepsis. Because the low
      intracellular calcium concentration plays an important role in the regulation of
      cellular function, an impairment in the ATP-dependent calcium uptake by
      endoplasmic reticulum during early and late sepsis may have a pathophysiologic
      significance in contributing to the development of altered hepatic metabolism
      during sepsis.

PMID- 9186468
TI  - Acidic conditions ameliorate both adenosine triphosphate depletion and the
      development of hyperpermeability in cultured Caco-2BBe enterocytic monolayers
      subjected to metabolic inhibition.
AB  - BACKGROUND: We recently reported that moderate degrees of adenosine triphosphate
      (ATP) depletion induced by chronic glycolytic inhibition or hypoxia increase the
      permeability of Caco-2BBe enterocytic monolayers. Interestingly, the development
      of lactic acidosis induced by anaerobic glycolysis ameliorates the development of
      hyperpermeability caused by chronic ATP depletion. We sought to further elucidate
      the mechanism(s) responsible for the apparent protection against epithelial
      hyperpermeability afforded by mild acidosis under conditions of metabolic
      inhibition. METHODS: Caco-2BBe monolayers growing on permeable supports in
      bicameral chambers were incubated with 2-deoxyglucose (2DOG) in a glucose-free
      (Glu-) environment to inhibit glycolysis. Permeability was determined by
      measuring the transepithelial flux of fluorescein sulfonic acid. Concentrations
      of intracellular calcium [Ca2+]i were determined fluorometrically by using fura
      2. RESULTS: When extracellular pH (pH0) was maintained at 7.4 or 5.5, incubation
      of monolayers for 24 hours with Glu-/2DOG increased permeability and depleted
      intracellular ATP levels. However, keeping pH0 at 7.0 to 6.0 ameliorated both the
      development of hyperpermeability and the depletion of ATP induced by Glu-/2DOG.
      These protective effects were observed under acidic conditions created either by
      addition to the medium of HCl or by incubation under an atmosphere containing 20%
      CO2. Incubation with Glu-/2DOG caused bulging of the apical membranes of cells
      (electron microscopy) and derangements in the perijunctional distribution of
      actin (fluorescence microscopy); however, these structural changes were
      ameliorated by mild acidosis. Acute chemical hypoxia at pH0 7.4 induced by Glu
      /2DOG plus antimycin A decreased cellular ATP levels and elevated [Ca2+]i.
      Lowering pH0 to 6.8 ameliorated both the depletion of ATP and the increase in
      [Ca2+]i induced by Glu-/2DOG+antimycin A. CONCLUSIONS: Moderate decreases in pH
      ameliorate the hyperpermeability induced by metabolic inhibition, possibly by
      diminishing ATP depletion and blunting increases in [Ca2+]i.

PMID- 9186469
TI  - Effect of anti-intercellular adhesion molecule-1 and anti-leukocyte function
      associated antigen-1 monoclonal antibodies on rat-to-mouse cardiac xenograft
      rejection.
AB  - BACKGROUND: The interaction between intercellular adhesion molecule-1 (ICAM-1)
      and its ligand, leukocyte function associated antigen-1 (LFA-1), is especially
      relevant in allograft rejection. We have previously shown that the simultaneous
      blockade of ICAM-1 and LFA-1 by monoclonal antibodies (mAbs) results in specific
      immunologic tolerance to cardiac allograft in a mouse model. METHODS: We
      evaluated the roles of these adhesion molecules in xenograft rejection by using a
      rat-to-mouse concordant xenograft model to identify critical molecules for
      immunosuppression. RESULTS: Lewis rat hearts transplanted into C3H/He mice were
      rejected within 5 to 7 days without treatment. A significant prolongation of
      xenograft survival (mean survival time, 11.6 days) was observed after treatment
      with anti-rat ICAM-1 and anti-mouse LFA-1 mAbs, when compared with nontreated
      mice or mice treated with different combinations of mAbs. Graft survival was
      prolonged in mice treated with FK506 (1 mg/kg/day), anti-rat ICAM-1, and anti
      mouse LFA-1 mAbs (mean survival time, 22.2 days), whereas the same dose of FK506
      alone was not effective. The mixed lymphocyte reaction showed that a combination
      of mAbs against mouse LFA-1-rat ICAM-1 and rat LFA-1-mouse ICAM-1 significantly
      inhibited the proliferation of mouse responders to rat stimulators and rat
      responders to mouse stimulators, respectively. Infiltration of mouse CD4
      positive, mouse CD8 positive, and mouse LFA-1 positive cells, as well as dense
      deposition of mouse immunoglobulin G (IgG), IgM, and up-regulation of rat ICAM-1,
      on the graft endothelial cells were demonstrated by immunopathologic analysis of
      the rejected hearts. Flow cytometric analysis with rat spleen cells demonstrated
      the presence of xenoreactive antibodies (mouse IgG and IgM) in the recipient's
      serum. This xenoreactive antibody production was delayed but not inhibited by
      treatment of the recipients with anti-rat ICAM-1 and anti-mouse LFA-1.
      CONCLUSIONS: Blockade of the donor side ICAM-1 and the recipient side LFA-1 is
      critical for immunosuppression with anti-ICAM-1-LFA-1 treatment. Humoral factors
      may be responsible for xenograft rejection that occurs even after inhibition of
      the cell-mediated immune response by anti-ICAM-1 and anti-LFA-1 mAbs.

PMID- 9186470
TI  - Functional capacity of the liver after two-thirds partial hepatectomy in the rat.
AB  - BACKGROUND: Liver cell proliferation after partial hepatectomy in rats has been
      thoroughly investigated. Although DNA synthesis and morphologic restoration have
      been studied in this rat model, the functional capacity of the remnant liver
      during regeneration has not been elucidated. METHODS: We measured the indocyanine
      green disappearance rate (ICG-k) and serum aminopyrine (CLamp) in rats at various
      intervals after two-thirds hepatectomy. Morphologic restoration of the liver
      after hepatectomy was evaluated on the basis of remnant liver weight,
      proliferating cell nuclear antigen labeling index, and the DNA content of the
      regenerating liver. Serial changes in ICG-k and CLamp after two-thirds
      hepatectomy were compared with the degree of morphologic restoration. RESULTS:
      ICG-k and CLamp were reduced by one third in rats after two-thirds hepatectomy.
      Although the rate of restoration of remnant liver weight was steady after
      hepatectomy, ICG-k and CLamp were lowest about 36 hours after hepatectomy. The
      restoration of ICG-k was comparable to that of liver weight, but the restoration
      of CLamp was delayed. CONCLUSIONS: Functional liver capacity was minimal during
      parenchymal cell mitosis in the regenerating liver. Functional restoration after
      two-thirds hepatectomy was delayed in comparison with morphologic restoration in
      rat.

PMID- 9186471
TI  - Extended right posterior segmentectomy for metastatic liver tumors.

PMID- 9186472
TI  - Spontaneous vocal cord paresis and return to normocalcemia: an unusual
      presentation of parathyroid adenoma with concomitant abscess.

PMID- 9186473
TI  - Postoperative bleeding induced by topical bovine thrombin: report of two cases.

PMID- 9186474
TI  - Differentiation of multifocal and multicentric hepatocellular carcinomas by DNA
      fingerprint analysis: case report.

PMID- 9186475
TI  - Familial papillary carcinoma of the thyroid.

PMID- 9186476
TI  - Inguinal hernia repair with flap of the anterior sheath of the rectus muscle:
      preliminary study.

PMID- 9186477
TI  - Study of interleukin-10 and experimental acute pancreatitis.

PMID- 9186478
TI  - Hexokinase inactivation induced by ascorbic acid/Fe(II) in rabbit erythrocytes is
      independent of glutathione-reductive processes and appears to be mediated by
      dehydroascorbic acid.
AB  - Recent studies performed in our laboratory demonstrated that rabbit red blood
      cell hexokinase was remarkably inhibited by the cocktail ascorbic acid/Fe(II)
      (Stocchi et al., 1994, Arch. Biochem. Biophys. 311, 160-167) and that the
      formation of dehydroascorbic acid was a key event in this process (Fiorani et
      al., 1996, Arch. Biochem. Biophys, 334, 357-361). The present study was
      undertaken to determine the final hexokinase-inactivating species using cell-free
      extract as a model. Our results demonstrate superimposable kinetics of hexokinase
      decay promoted by either ascorbic acid/Fe(II) or dehydroascorbic acid in
      erythrocyte lysates in which the reduced glutathione (GSH) levels were variously
      manipulated. In particular, neither removal nor addition of this tripeptide was
      able to significantly alter the rate or extent of hexokinase inhibition. Thus,
      GSH-reductive processes are dispensable events in the process of hexokinase
      inhibition promoted by ascorbic acid/Fe(II) in red blood cells. As a consequence,
      dehydroascorbic acid appears to be the species which directly inhibits
      hexokinase. This inference is further supported by the observation that addition
      of dehydroascorbic acid to the purified enzyme leads to a remarkable inhibition
      in its activity.

PMID- 9186479
TI  - Pterin and folate reduction by the Leishmania tarentolae H locus short-chain
      dehydrogenase/reductase PTR1.
AB  - Overproduction of the short-chain dehydrogenase/reductase PTR1 confers resistance
      to the dihydrofolate reductase inhibitor methotrexate in the protozoan parasite
      Leishmania. Genetic analysis has previously implicated PTR1 in pterin and folate
      metabolism. PTR1 was purified from a fusion protein expressed in Escherichia
      coli. Purified PTR1 exhibits NADPH-dependent biopterin, dihydrobiopterin, folate,
      and dihydrofolate reductase activities. The highest activity was found with the
      most oxidized pterins. The active protein was found to be a tetramer as
      demonstrated by gel-filtration chromatography. Kinetic constants (K(m)), as
      determined by double-reciprocal plots, were calculated for NADPH and for several
      of PTR1's substrates. The PTR1 of Leishmania tarentolae had a K(m) of 16.9 microM
      for the cofactor NADPH and K(m) values ranging from 3.5 to 85 microM for the
      various substrates. The dissociation constant (KD), as determined by fluorescence
      titration, for NADPH was estimated to be 130 microM. The biochemical
      characterization of this important and novel enzyme involved in folate and pterin
      metabolism of Leishmania should be useful for structure-function analysis and for
      developing specific inhibitors against this putative important chemotherapeutic
      target.

PMID- 9186480
TI  - Mechanical loading and TGF-beta regulate proteoglycan synthesis in tendon.
AB  - Fibrocartilage is found in tendon at sites where the tissue is subjected to
      transverse compressive loading in vivo. A significant characteristic of the
      tissue transition from tendon to fibrocartilage in bovine deep flexor tendon is
      increased gene expression, synthesis, and accumulation of both a large
      proteoglycan, aggrecan, and a small proteoglyoan, biglycan. In order to
      investigate the cellular events involved in this response, segments of fetal
      bovine deep flexor tendon were subjected in vitro to cyclic compressive load for
      72 h. Following loading, the level of aggrecan mRNA in cells from loaded tissue
      was increased 200-450% compared to matched nonloaded tissue segments, as
      determined by slot-blot analysis. The level of biglycan mRNA increased 100%, and
      the level of versican mRNA increased 130% in the loaded tissue. The level of
      decorin mRNA remained virtually unchanged, while expression of alpha 1(I)
      collagen increased only 40%. When tissue segments were cultured in the presence
      of transforming growth factor (TGF)-beta 1 (1 ng/ml), the synthesis and
      expression of mRNA for both aggrecan and biglycan increased, whereas decorin
      expression was not affected. Similarity in both the direction and the pattern of
      the cellular response to mechanical load and TGF-beta suggested a causal
      relationship. Both loading of tendon segments and TGF-beta treatment increased
      expression of mRNA for TGF-beta by approximately 40% compared to control tissue.
      In addition, the amount of newly synthesized TGF-beta immunoprecipitated from
      extracts of loaded tissue was several-fold greater than that from nonloaded
      tissue. The experiments of this study support a hypothesis suggesting that one
      aspect of the response of cells in fetal tendon to compressive load is increased
      TGF-beta synthesis which, in turn, stimulates synthesis of extracellular matrix
      proteoglycans and leads toward fibrocartilage formation.

PMID- 9186481
TI  - Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex
      steroids.
AB  - Based on enzyme activity, protein levels, and mRNA levels, we have previously
      demonstrated the female-predominant, female-specific, and gender-independent
      expression in mouse liver of FMO forms 1, 3, and 5, respectively. This study
      investigated the roles of testosterone, 17 beta-estradiol, and progesterone in
      the regulation of hepatic FMOs. FMO expression was examined in gonadectomized CD
      1 mice, normal CD-1 mice receiving hormonal implants, and gonadectomized mice
      receiving various hormonal treatments. Following castration of males, hepatic FMO
      activity levels were significantly increased and serum testosterone levels
      significantly decreased; however, administration of physiological levels of
      testosterone to castrated animals returned FMO activity and testosterone
      concentrations to control levels. When sexually intact and ovariectomized female
      mice were treated with testosterone, their hepatic FMO activity levels were
      reduced to those of their male counterparts, concomitant with high serum
      testosterone levels. In males, castration dramatically increased FMO3 and FMO1
      expression, and testosterone replacement to castrated males resulted in ablation
      of FMO3 expression. In addition, testosterone administration to females (sexually
      intact and gonadectomized animals) reduced FMO1 expression and obviated FMO3
      expression. In females, ovariectomy alone slightly reduced FMO activity,
      indicative of a possible stimulatory role of female sex steroids; however, female
      FMO isozyme expression was relatively unchanged, and hormone replacement therapy
      to ovariectomized females had no discernible effect. In males and females, FMO5
      levels were unaffected by gonadectomy or hormone administration, thus indicating
      a sex hormone-independent mechanism of regulation for this isoform.
      Interestingly, FMO1 protein levels were increased in sexually intact males
      following treatment with 17 beta-estradiol; however, only a slight increase in
      FMO3 protein level was observed. No positive hormone effectors of female FMO
      expression were identified.

PMID- 9186482
TI  - NADH oxidase activity from sera altered by capsaicin is widely distributed among
      cancer patients.
AB  - A cancer-specific form of NADH oxidase inhibited or stimulated by 1 or 100 microM
      capsaicin (8-methyl-N-vanillyl-6-noneamide) is present in sera from cancer
      patients. The capsaicin-inhibited NADH oxidase activity appears to be absent from
      sera of individuals free of cancer. The capsaicin-inhibited activity is present
      both in freshly collected sera and in sera stored frozen for varying periods of
      time. For the latter, an assay was carried out under renaturing conditions in the
      presence of NADH and reduced glutathione followed by dilute hydrogen peroxide.
      Inhibition was half maximal at about 1 microM capsaicin. The capsaicin-inhibited
      activity was found in sera over a broad spectrum of cancer patients including
      patients with solid cancers (e.g., breast, prostate, lung, ovarian) as well as
      with leukemias and lymphomas.

PMID- 9186483
TI  - Diclofenac sodium and mefenamic acid: potent inducers of the membrane
      permeability transition in renal cortex mitochondria.
AB  - The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to induce Ca(2+)
      mediated/cyclosporin A-sensitive mitochondrial membrane permeability transition
      (MMPT) was evaluated by monitoring swelling of isolated rat renal cortex
      mitochondria in the presence of 20 microM CaCl2. Dipyrone and paracetamol did not
      induce MMPT, while piroxicam and acetylsalicylic acid (and its metabolite
      salicylate) were poor inducers. In contrast, diclofenac sodium and mefenamic acid
      were potent triggering agents, inducing MMPT at 2 microM, a concentration below
      those previously shown to uncouple and/or inhibit oxidative phosphorylation. When
      compared to salicylate, a classical uncoupler and inducer of MMPT, the potency of
      diclofenac sodium and mefenamic acid was about 50-fold greater. Swelling was
      completely prevented by EGTA, cyclosporin A, or MgCl2, and only partially by ADP
      or dithiothreitol. Under the same experimental conditions as for the swelling
      assays, the drugs depressed the membrane potential of mitochondria, an effect
      prevented by cyclosporin A and restored by EGTA. Also, the drugs did not induce
      membrane lipid peroxidation or changes in GSSG levels, but led to a small
      decrease in protein thiol content, as well as to a substantial decrease in the
      NADPH levels of mitochondria. Hence, membrane depolarization and pyridine
      nucleotide oxidation seem to be involved in MMPT induction by these NSAIDs. The
      potency in eliciting the process, like the uncoupling activity, seems to be
      influenced by the lipophilic character of the molecules.

PMID- 9186485
TI  - Identification and mutational analysis of the immunodominant IgE binding epitopes
      of the major peanut allergen Ara h 2.
AB  - A major peanut allergen, Ara h 2, is recognized by serum IgE from > 90% of
      patients with peanut hypersensitivity. Biochemical characterization of this
      allergen indicates that it is a glycoprotein of approximately 17.5 kDa. Using N
      terminal amino acid sequence data from purified Ara h 2, oligonucleotide primers
      were synthesized and used to identify a clone (741 bp) from a peanut cDNA
      library. This clone was capable of encoding a 17.5-kDa protein with homology to
      the conglutin family of seed storage proteins. The major linear immunoglobulin E
      (IgE)-binding epitopes of this allergen were mapped using overlapping peptides
      synthesized on an activated cellulose membrane and pooled serum IgE from 15
      peanut-sensitive patients. Ten IgE-binding epitopes were identified, distributed
      throughout the length of the Ara h 2 protein. Sixty-three percent of the amino
      acids represented in the epitopes were either polar uncharged or apolar residues.
      In an effort to determine which, if any, of the 10 epitopes were recognized by
      the majority of patients with peanut hypersensitivity, each set of 10 peptides
      was probed individually with serum IgE from 10 different patients. All of the
      patient sera tested recognized multiple epitopes. Three epitopes (aa27-36, aa57
      66, and aa65-74) were recognized by all patients tested. In addition, these three
      peptides bound more IgE than all the other epitopes combined, indicating that
      they are the immunodominant epitopes of the Ara h 2 protein. Mutational analysis
      of the Ara h 2 epitopes indicate that single amino acid changes result in loss of
      IgE binding. Two epitopes in region aa57-74 contained the amino acid sequence
      DPYSP that appears to be necessary for IgE binding. These results may allow for
      the design of improved diagnostic and therapeutic approaches to peanut
      hypersensitivity.

PMID- 9186484
TI  - 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran: design and
      evaluation as a novel radical-scavenging antioxidant against lipid peroxidation.
AB  - To develop a novel potent radical-scavenging antioxidant, the ideal structure of
      a phenolic compound was designed considering the factors that determine
      antioxidant potency. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4, 6-di-tert
      butylbenzofuran (BO-653) was thus synthesized and its antioxidant activity was
      evaluated against lipid peroxidations in vitro. The electron spin resonance study
      showed that the phenoxyl radical derived from BO-653 was more stable than alpha
      tocopheroxyl radical. BO-653 reduced alpha-tocopheroxyl radical rapidly, but
      alpha-tocopherol did not reduce the phenoxyl radical derived from BO-653.
      However, the chemical reactivity of BO-653 toward peroxyl radical was smaller
      than that of alpha-tocopherol. This was interpreted as the steric effect of bulky
      tert-butyl groups at both ortho positions which hindered the access of peroxyl
      radical to the phenolic hydrogen. However, the tertbutyl substituents increased
      the stability of BO-653 radical and also lipophilicity, and its antioxidant
      potency against lipid peroxidation in phosphatidylcholine liposomal membranes was
      superior to that of alpha-tocopherol. Ascorbic acid reduced the phenoxyl radical
      derived from BO-653 and spared BO-653 during the oxidation of lipid in the
      homogeneous solution. On the other hand, ascorbic acid did not spare BO-653 in
      the oxidation of liposomal membranes. It was concluded that BO-653 is a potent
      novel radical-scavenging antioxidant.

PMID- 9186486
TI  - Quantitation of 3-deoxyglucosone levels in human plasma.
AB  - 3-Deoxyglucosone (3DG), a reactive dicarbonyl, is an important intermediate in
      the formation of advanced glycation end products (AGEs). The AGEs are
      particularly important in diabetes since they have been correlated with the
      development of diabetic complications. Consequently, measurements of 3DG are
      likely to provide valuable insights into the role of this metabolite in the
      etiology of diabetic complications. While several methods of 3DG quantitation in
      human plasma have been previously published, a significant discrepancy (over 30
      fold) exists in the reported values. Knecht et al. (Arch. Biochem. Biophys. 294,
      130-137, 1992) have reported the levels of plasma 3DG in normoglycemics to be 61
      nM, using a GC/MS procedure. In contrast to this, Niwa et al. (Biochem. Biophys.
      Res. Commun. 196, 837-843, 1993) reported 3DG levels to be 1800 nM in
      normoglycemics, using a totally independent GC/MS method. To resolve this
      disagreement and fill the need for a robust assay for this dicarbonyl, suitable
      for absolute quantitation, a GC/MS procedure was devised for its measurement.
      Plasma samples were deproteinized either by ultrafiltration or by addition of
      ethanol as described by Niwa et al. (Biochem. Biophys. Res. Commun. 196, 837-843,
      1993). 3DG in the ultrafiltrate or the supernatant was conjugated with 2,3
      diamino-naphthalene to produce a stable adduct which was then converted to a
      silyl ether and analyzed by GC/MS. The analyte was monitored by selected ion
      monitoring at an m/z of 295 and 306 and quantitated using an internal standard of
      [U-13C]3DG. Using this approach, 3DG levels in plasma deproteinized by
      ultrafiltration were found to be significantly elevated from 58.5 +/- 14 (SD) nM
      in normoglycemics to 98.5 +/- 34 (SD) nM in type I diabetics. When
      deproteinization of the plasma was carried out using ethanol, the levels of 3DG
      from normoglycemic plasma were similar to those reported by Niwa et al. (1710 +/-
      750 (SD) nM). These results suggest that 3DG levels measured by ultrafiltration
      may represent the free circulating 3DG and those obtained by ethanol extraction
      may represent aform of 3DG bound to a macromolecule (presumbaly protein).

PMID- 9186487
TI  - Activation of human neutrophil procollagenase by nitrogen dioxide and
      peroxynitrite: a novel mechanism for procollagenase activation involving nitric
      oxide.
AB  - The involvement of nitric oxide (NO) and its reactive intermediates such as
      nitrogen dioxide (NO2) and peroxynitrite (ONOO-) in the activation of matrix
      metallo-proteinase was investigated. The human neutrophil procollagenase (matrix
      metalloproteinase-8) (M(r), 85 kDa) was purified to homogeneity from human
      neutrophils by using column chromatography. After incubation of human neutrophil
      procollagenase with various nitrogen oxide-generating systems, collagenolytic
      activity in each reaction system was measured. In addition, neutrophil
      collagenase activity was determined by assessment of proteolysis of human alpha 1
      protease inhibitor. NO was formed by the propylamine NONOate, and NO2 was
      generated by oxidation of NO with 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO). NO2, formed by NONOate and
      carboxy-PTIO, and the synthetic ONOO- exhibited strong activation of the
      procollagenase at 1-20 microM. Significant activation of the procollagenase was
      observed with use of authentic NO2 gas as well. Constant flux infusion of ONOO-
      into the procollagenase solution resulted in stronger procollagenase activation
      than did a bolus addition of ONOO- to the reaction mixture. However, NO showed
      only weak activating potential under the aerobic (ambient) condition; an NO
      concentration of more than 10 mM was needed for appreciable activation of the
      procollagenase. Of considerable importance was the fact that NO participates in
      activation of the neutrophil collagenase through its conversion to NO2 or ONOO-
      in human neutrophils. These results suggest that NO2 and ONOO- may be potent
      activators of human neutrophil procollagenase.

PMID- 9186489
TI  - Free and protein-associated nitrotyrosine formation following rat liver
      preservation and transplantation.
AB  - Nitrotyrosine in human and animal tissues has been associated with pathologic
      conditions such as atherosclerosis, renal failure, and acute lung disease. In
      this study, free and protein-associated nitrotyrosine were determined in plasma
      and tissue samples using a dual-channel electrochemical detection method. Free
      nitrotyrosine was quantified in acetonitrile-extracted samples while protein
      associated nitrotyrosine was determined in proteinase K-digested samples. In
      human plasma, total nitrotyrosine increased from 2.3 to 4.3 and 13.2 mumol/mol
      Tyr following addition of 0, 0.5, and 1 mM ONOO-. To determine if nitrotyrosine
      was produced during ex vivo hypothermic preservation, rat livers were stored in
      University of Wisconsin solution (UW) for 0, 6, or 8 h and reperfused for 3 h.
      Total nitro-tyrosine increased 359 and 908% after 6 and 8 h preservation compared
      to 0 h. To determine if nitrotyrosine was produced in vivo following hepatic
      ischemia, a rat preservation-transplantation model was utilized in which livers
      were flushed with cold UW (0-h group) or transplanted following 6 h hypothermic
      preservation in UW. Free nitrotyrosine increased from 15.7 +/- 0.3 in the 0-h
      group to 23.6 +/- 2.5 mumol/mol Tyr, 24 h posttransplant of 6-h preserved livers.
      Protein-associated nitrotyrosine increased from 9.5 +/- 1.1 in the 0-h group to
      27.5 +/- 0.7 mumol/mol Tyr in the 6-h preservation-transplantation group. Protein
      associated nitrotyrosine provides an integrative determination of nitration.
      Detection of free and protein-associated nitrotyrosine in biologic samples may
      allow insight into the role of .NO-derived oxidants in tissue injury associated
      with various pathologic conditions.

PMID- 9186488
TI  - Participation of reactive oxygen species in phototoxicity induced by quinolone
      antibacterial agents.
AB  - To elucidate the mechanism of phototoxicity induced as a side effect by some of
      the new quinolone antibiotics, we studied sparfloxacin (SPFX), lomefloxacin,
      enoxacin, ofloxacin, and ciprofloxacin. We first examined the photosensitized
      formation of reactive oxygen species such as singlet oxygen (1O2) and superoxide
      anion (O2-) mediated by the new quinolones. Although a large number of studies
      have been reported, there is no direct evidence that these drugs generate
      reactive oxygen species. We employed a near-infrared emission spectrometer to
      detect 1O2-specific emission (1268 nm), and the nitroblue tetrazolium reduction
      method to detect O2-. All the quinolones investigated in this study were found to
      produce 1O2. Four drugs, but not SPFX, produced O2-. We also examined
      photodynamic DNA strand-breaking activity as a possible mechanism to explain the
      participation of reactive oxygen species in the phototoxicity of the drugs. All
      the drugs exhibited photodynamic DNA strand-breaking activity. The inhibitory
      effect of scavengers of reactive oxygen species indicated that the main active
      species was 1O2. The DNA strand-breaking activity was correlated not with the 1O2
      forming ability, but with the affinity of the drugs for DNA. This result may be
      due to the short lifetime of 1O2. These data suggested that the phototoxicity of
      the new quinolones was related to DNA damage caused by reactive oxygen species,
      especially 1O2.

PMID- 9186490
TI  - Reactivity of mu-peroxo-bridged dimeric vanadate in bromoperoxidation.
AB  - Diglycyl triperoxodivanadate [V2O2(O2)3(Gly H)2(H2O)2], a synthetic compound with
      mu-peroxo-bridge derived from H2O2 and vanadate, oxidized bromide to a
      bromination-competent intermediate in phosphate buffer and physiological pH. This
      is in contrast to the requirement of acid medium with H2O2 as the oxidant.
      Addition of its solid to bromide solution instantly produced a 262-nm-absorbing
      compound that converted phenol red (a trap) to its 592-nm-absorbing bromo
      derivative. The high bromination activity was lost on dissolving this compound in
      water and the solution showed the presence of peroxovanadates (mono and di) and
      vanadates (V1 and oligomeric V10) in 51V-NMR spectrum. Of these, diperoxovanadate
      and vanadate together supported slow bromination activity by a second set of
      reactions including bromide-assisted reductive formation of vanadyl. Bromination
      activity dependent on vanadyl was sensitive to oxidation by excess H2O2 and to
      complexation by EDTA, whereas that of triperoxodivanadate was relatively
      insensitive. Vanadyl and diperoxovanadate are capable of forming a mu-peroxo
      bridged complex that is essentially similar to the synthetic vanadate dimer used
      in the present experiments. It appears that a mu-peroxo-intermediate is the
      proximal oxidant of bromide in vanadium-catalyzed bromoperoxidation.

PMID- 9186491
TI  - Putative folding pathway of insulin-like growth factor-I.
AB  - Insulin-like growth factor-I (IGF-I) has three disulfide bonds and refolding of
      the fully reduced molecule generates varying ratios of correctly (PII) and
      incorrectly (PI) folded forms via several intermediates. All of the intermediates
      have the disulfide bond between Cys18 and 61 formed, indicating that formation of
      this disulfide is the first step in refolding. In order to further understand the
      refolding pathway, two intermediate froms, PIII with the additional disulfide
      Cys(6/47) formed and PIIIa with Cys(6/48) formed, were isolated. The oxidation of
      the remaining Cys48 and 52 in PIII and Cys47 and 52 in PIIIa would lead to PI and
      PII, respectively; however, air oxidation of these resulted in a rapid
      reshuffling into other intermediates as well as folding into the fully oxidized
      forms, and this occurred whether refolding was started with PIII or PIIIa. When
      oxidation occurred in the presence of an excess of oxidized glutathione, the
      predominant species generated were various glutathione adducts regardless of the
      initial intermediate form, indicating that formation of the last disulfide bond
      is not a favorable process relative to disulfide exchange when excess disulfides
      from oxidized glutathione are present. Interestingly, if 80 microM copper
      sulfate, an oxidant, is added to the refolding buffer, PIII resulted in formation
      of the PI form alone, whereas PIIIa resulted in the PII form alone. It was
      concluded from these results that the intermediate forms of IGF-1 can rapidly
      reshuffle between different disulfide structures, and that formation of the last
      disulfide bond is not as favorable a process as the conversion to other
      intermediates. The oxidation to form the last disulfide bond in PIII or PIIIa is
      accelerated and hence the interconversion to other intermediates is kinetically
      minimized only in the presence of copper sulfate. It appears, therefore, that the
      two intermediate forms, PIII and PIIIa, are the precursors of the corresponding
      fully oxidized forms, but their conversions are not energetically a favorable
      process.

PMID- 9186492
TI  - Stopped-flow kinetics reveal multiple phases of thioflavin T binding to Alzheimer
      beta (1-40) amyloid fibrils.
AB  - The benzothiazole dye thioflavin T (ThT) is a classical amyloid stain for senile
      plaques containing beta/A4 peptide in Alzheimer's disease brain. ThT also binds
      rapidly and specifically to the anti-parallel beta-sheet fibrils formed from
      synthetic beta (1-40) peptide, but does not bind to monomer or oligomeric
      intermediates. The fibrillar beta-sheet-bound dye species undergoes a
      characteristic 120 nm red shift of its excitation spectrum that may be
      selectively excited at 450 nm, resulting in a fluorescence signal at 482 nm.
      Mixing of preformed beta (1-40) amyloid fibrils with ThT in a stopped-flow
      spectrophotometer, monitoring fluorescence emission at > 475 nm while exciting at
      450 nm, distinguished multiple kinetic phases of roughly equivalent amplitude
      with tau's in the ranges of 0.007, 0.05, 0.75, and 10-20 s. The fastest reaction
      appears to reflect a bimolecular dye binding event while the remaining reactions
      are rate-limited by protein tertiary or quaternary conformational changes. The
      high activation energies of the three slower reactions support this
      interpretation. The ThT concentration dependence of the reaction rates at
      different ratios of ThT/beta (1-40) amyloid fibrils rules out a rate-limiting
      conformational change occurring prior to ligand binding. ThT is a useful probe
      for the aggregated fibrillar state of beta (1-40) amyloid fibrils as the amyloid
      specific fluorescence reports only fibrillar species. The binding of ThT does not
      interfere with the aggregation of this peptide into amyloid fibrils. The putative
      conformational changes detected by the ThT fluorescence suggest that small
      pharmacologic ligands can perturb and possibly dissociate A beta amyloid fibrils.

PMID- 9186493
TI  - Kinetics of enzymes with iso-mechanisms: solvent isotope effects.
AB  - Kinetic isotope effects on enzymatic reactions which employ general acid or
      general base catalytic mechanisms may arise during reprotonations of free enzyme.
      These effects reveal kinetically significant isomerizations of the free enzyme,
      or iso-mechanisms. The effects are expressed kinetically at high concentrations
      of substrate, on Vmax or Kcat, but only thermodynamically at low substrate, on
      Vmax/K(m). The effects are also expressed on the noncompetitive inhibition
      constant of product inhibition, Kiip, because this parameter is dependent upon
      the steady-state concentration of the product form of free enzyme. A normal
      isotope effect on isomerization will decrease Vmax and Kiip, but not necessarily
      to the same degree. Which is greater will depend upon how rate-limiting the
      isomerization is to a complete turnover. Together they are related to the full
      effect on isomerization, DKiso, by their product: DKiso = DVmax DKiip. Moreover,
      precisely how rate-limiting the isomerization is to a turnover can be shown to be
      numerically equal to (DVmax - 1)/(DKiipDVmax - 1), which surprisingly, holds
      whether there are other isotope effects present or not. The new relationships
      applied to published data on bovine carbonic anhydrase II reveal an intrinsic
      solvent isotope effect of DK = 9 +/- 4, and an iso step that is less than 80%
      rate-limiting. Applied to porcine pepsin, a significant DV is accompanied by
      excessive standard error on DKiip, precluding the calculation of a definitive
      intrinsic solvent isotope effect.

PMID- 9186494
TI  - Inhibition of lung surfactant secretion from alveolar type II cells and annexin
      II tetramer-mediated membrane fusion by phenothiazines.
AB  - We investigated the effects of phenothiazines on lung surfactant secretion from
      rat alveolar epithelial type II cells and on annexin II tetramer (Anx IIt)
      mediated membrane fusion. Trifluoperazine and promethazine inhibited ATP
      stimulated phosphatidylcholine (PC) secretion from type II cells in a dose
      dependent manner. Concentrations that cause 50% inhibition (IC50) were
      approximately 3 and 25 microM for trifluoperazine and promethazine, respectively.
      Promethazine also inhibited PC secretion of type II cells stimulated by other
      secretagogues, including calcium ionophore A23187, phorbol 12-myristate 13
      acetate, and terbutaline that are known to stimulate PC secretion via different
      signal transduction pathways. Since we have recently determined that Anx IIt is
      involved in PC secretion of type II cells, we examined whether phenothiazines
      influence Anx IIt's activity. Trifluoperazine and promethazine inhibited Anx
      IIt's ability to aggregate phosphatidylserine (PS) liposomes, to fuse
      PS/phosphatidylethanolamine (PE) liposomes, and to fuse PS/PE liposomes with
      lamellar bodies. These results suggest a relationship between lung surfactant
      secretion and Anx IIt-mediated membrane fusion.

PMID- 9186495
TI  - Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with
      cytochrome P450 3A4 and other forms: effects of cytochrome P450-P450 and
      cytochrome P450-b5 interactions.
AB  - Tolbutamide methyl hydroxylation and S-warfarin 7-hydroxylation activities were
      reconstituted in systems containing recombinant human cytochrome P450 (P450 or
      CYP) 2C10(2C9) and the optimal conditions for the systems were compared with
      those of bufuralol 1'-hydroxylation by CYP1A1, theophylline 8-hydroxylation by
      CYP1A2, bufuralol 1'-hydroxylation by CYP2D6, chlorzoxazone 6-hydroxylation by
      CYP2E1, and testosterone 6 beta-hydroxylation by CYP3A4. CYP2C10 required
      cytochrome b5 (b5) for optimal rates of tolbutamide and S-warfarin oxidations and
      b5 could be replaced by apo-b5; apo-b5 and b5 effects on the reconstituted
      systems have already been reported in systems containing CYP3A4 for the oxidation
      of testosterone and nifedipine and for the rapid reduction of CYP3A4 by NADPH
      P450 reductase (H. Yamazaki et al., 1996, J. Biol. Chem. 271, 27438-27444).
      Stopped-flow studies, however, suggested that apo-b5 as well as b5 did not cause
      stimulation of the reduction of CYP2C10 by NADPH-P450 reductase, while the
      reduction rates were dependent on the substrates in reconstituted systems.
      Chlorzoxazone 6-hydroxylation by CYP2E1 was stimulated by b5, but not by apo-b5,
      in reconstituted systems. Neither apo- nor holo-b5 increased bufuralol 1'
      hydroxylation activity by CYP1A1 or 2D6 or theophylline 8-hydroxylation by
      CYP1A2. Interestingly, we found that testosterone 6 beta-hydroxylation by CYP3A4
      was stimulated by CYP1A2 (and also by a modified form in which the first 36
      residues of the native human protein were removed) and CYP1A1 as well as by b5,
      and such stimulations were not seen when other P450 proteins (e.g., CYP2C10, 2D6,
      or 2E1) were added to the reconstituted systems. In contrast, substrate
      oxidations by CYP2C10 and CYP2E1 were not stimulated by other P450 proteins. The
      present results suggest that there are differences in optimal conditions for
      reconstitution of substrate oxidations by various forms of human P450 enzymes,
      and in some P450-catalyzed reactions protein-protein interactions between P450
      and b5 and other P450 proteins are very important in some oxidations catalyzed by
      CYP2C10, 2E1, and 3A4.

PMID- 9186496
TI  - Functional effects of amino acid substitutions at residue 33 of human thymidylate
      synthase.
AB  - Fluorinated pyrimidines, such as 5-fluorouracil (FUra) and 5-fluoro-2'
      deoxyuridine (FdUrd), are cytotoxic to cells as a consequence of generation of 5
      fluoro-2'-deoxyuridylate (FdUMP), which is a mechanism-based inhibitor of the
      enzyme thymidylate synthase (TS). FdUMP inhibits TS via its binding into a stable
      inhibitory ternary complex (ITC) with the enzyme and the cosubstrate N5, N10
      methylene-5,6,7,8-tetrahydrofolate (CH2H4PteGlu). In previous studies, we
      identified a naturally occurring mutant form of human TS that contains a Tyr-
      >His substitution at residue 33 and confers relative resistance to FdUrd in both
      mammalian and bacterial cells. Kinetic studies indicated that the equilibrium
      dissociation constant (Kd) for binding of FdUMP into the ITC is altered in the
      mutant enzyme. In the current investigation, we have examined the kinetics of
      FdUMP binding into covalent binary complexes, i.e., in the absence of
      CH2H4PteGlu. Our results showed that although the rate constants for binary FdUMP
      binding (i.e., kon and koff) are altered by the Tyr-->His substitution, there is
      no measurable effect on the overall Kd. Analysis of a number of other amino acid
      substitutions at residue 33 indicated that maximal enzyme accumulation and
      function requires a bulky, hydrophobic side chain at this site.

PMID- 9186497
TI  - The erythropoietin-sensitive membrane phosphoprotein, pp43, is a protein
      serine/threonine kinase.
AB  - We have shown previously that treatment of isolated erythroid cell plasma
      membranes with erythropoietin leads to a rapid decrease in pp43, an
      erythropoietinsensitive membrane phosphoprotein (Choi, H. S., Wojchowski, D. M.,
      and Sytkowski, A. J., J. Biol. Chem. 262, 2933, 1987; Choi, H. S., Bailey, S. C.,
      Donahue, K. A., Vanasse, G. J., and Sytkowski, A. J., J. Biol. Chem. 265, 4143,
      1990). We have now demonstrated this effect in intact cells and have obtained
      further information regarding pp43 function during erythropoietin stimulation.
      32P-phosphorylated membranes were subjected to conditions of increasing pH.
      [32P]pp43 dissociated readily into solution, reaching half-maximal dissociation
      at pH approximately 9. This dissociation was enhanced markedly by increasing the
      ionic strength up to a maximum of 0.5 M KCl. These biochemical properties
      characterize pp43 as a membrane-associated protein. Addition of [gamma-32P]ATP to
      an aqueous supernatant prepared from unlabeled membranes resulted in the 32P
      phosphorylation of pp43 in solution, after dissociation from the plasma membrane.
      Furthermore, erythropoietin treatment of unlabeled, intact cells followed by
      fractionation and 32P-phosphorylation resulted in a striking erythropoietin- and
      time-dependent increase in [32P]pp43 found in the supernatant and a concomitant
      decrease in [32P]pp43 found in the membrane pellet. This strongly suggests that
      erythropoietin stimulates the dissociation of pp43 from the plasma membrane and
      promotes translocation into the supernatant (cytoplasm). Using a renaturation
      kinase assay, we demonstrated that pp43 is capable of autophosphorylation on
      serine and threonine, thus identifying it as a new protein serine/threonine
      kinase. The results suggest a role for pp43 in transmembrane signaling.

PMID- 9186498
TI  - Evidence against formation of A23187 dimers and oligomers in solution: photo
      induced degradation of Ionophore A23187.
AB  - Ionophore A23187 has been proposed to form Ca(2+)- conducting channels that arise
      from dimers and oligomers of the compound (e.g., Balasubramanian, S. V., and
      Easwaran, K. R. K. (1989) Biochem. Biophys. Res. Commun. 158, 891-897). To
      investigate this possibility, the solution behavior of A23187 in chloroform, n
      hexane, ethanol, 80% methanol-water, and palmitoyloleoylphosphatidyl choline
      (POPC) vesicles was investigated using UV-VIS, circular dichroism (CD), and 1H
      NMR techniques. The concentration dependence of the UV-VIS and CD spectra
      obtained in freshly prepared chloroform solutions indicates that neutral A23187
      (HA) exists as a monomer for ionophore concentrations in the range of 50-1000
      microM. The cause of time- and concentration-dependent spectral alterations which
      gave rise to the dimer/channel hypothesis was also investigated. For solutions of
      50-1000 microM A23187 in chloroform, n-hexane, and ethanol stored in the dark, no
      spectral changes were observed for periods of 2 months. However, solutions in
      these solvents did show time-dependent spectral changes when exposed to light. In
      80% methanol-water or phospholipid vesicles, similar spectral changes were
      observed, even when the solutions were protected from light. Application of TLC
      and MS methods indicate that the time-dependent spectral changes reflect
      degradation of A23187, not dimer or oligomer formation. The degradative processes
      proceed with half-lives ranging from approximately 75 to > 400 h, and are
      influenced by several factors, including solvent, exposure to light, ionophore
      concentration, pH, and the presence of metal ions, EDTA, dissolved oxygen, and a
      radical inhibitor. The kinetics of Ca2+ transport into Quin-2-loaded POPC
      vesicles by authentic A23187 give no evidence of a channel mechanism, even
      following a previous and lengthy coincubation of the ionophore with the vesicles.

PMID- 9186499
TI  - Viral infection. I. Regulation of protein synthesis during vaccinia viral
      infection of animal cells.
AB  - Regulation of vaccinia viral infection was studied using three animal cell lines:
      KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (African green monkey
      kidney). KRC-7 is highly enriched in p67, a glycoprotein which protects eIF-2
      alpha-subunit from phosphorylation by eIF-2 kinases. We report: (i) At 5 pfu per
      cell of the virus, KRC-7 is resistant to the virus. Other cells are sensitive. At
      25 pfu per cell of the virus, KRC-7 is also sensitive to the virus. After
      productive viral infection, the cell extracts showed strong p67-DG activity and
      actively deglycosylated exogenous p67. After p67-deglycosylation, the cell
      extracts also phosphorylated eIF-2. (ii) The rate of synthesis of a major host
      protein (approximately 45 kDa) in infected L929 cells measured after 2 h of viral
      infection declined more than 50%. The rate declined thereafter. The rate of
      synthesis of host proteins in viral-resistant KRC-7 cells (infected with 5 pfu
      per cell of the virus) remained unchanged. The mechanism of resistance of KRC7
      cells to vacinia virus at 5 pfu per cell of the virus was investigated. The p67
      level in these cells was varied by growing the cells under different
      physiological conditions such as serum starvation and expression of p67-sense and
      p67-antisense DNA. At low p67 level in the cells, p67-DG is activated. This
      deglycosylates p67 and inactivates p67. This accompanies eIF-2 phosphorylation
      and shutoff of host protein synthesis. At high p67 level in the cells, activation
      of p67-DG is prevented. This prevents shut-off of host protein synthesis and
      viral growth.

PMID- 9186500
TI  - Viral infection. II. Hemin induces overexpression of p67 as it partially prevents
      appearance of an active p67-deglycosylase in baculovirus-infected insect cells.
AB  - The roles of p67-deglycosylase (p67-DG) in the regulation of protein synthesis in
      baculovirus-infected insect cells were studied. Like vaccinia viral infection,
      baculovirus infection of insect cells also induced the appearance of a p67-DG.
      However, p67-DG activity could not be detected because these cells do not contain
      a detectable level of p67. The baculovirus expression vector system (BEVS),
      however, promotes significant expression of cloned p67-cDNA. The expression of
      p67 was significantly enhanced by the addition of hemin to the growth medium.
      Maximum enhancement was observed at 5 microM hemin. Data suggest that hemin
      prevents the activation of latent p67-DG inside the cell and does not have any
      effect on p67 gene transcription. To gain a better understanding of the mechanism
      of p67-DG activation and hemin stimulation of p67 synthesis, we have now purified
      p67-DG from baculovirus-infected insect cells. We prepared antibodies against
      this protein. These antibodies reacted with a 105-kDa protein in cell extracts
      from the uninfected insect cells (Sf9), KRC-7, and L929 (animal cells). In
      addition, these antibodies reacted with an additional 60-kDa protein in the cell
      extracts of baculovirus-infected Sf9 cells and vaccinia virus-infected KRC-7 and
      L929 cells. Data are also presented to show that the antibodies against p67-DG
      reacted more efficiently (40%) with the 60-kDa protein in both hemin-deficient
      reticulocyte lysate and hemin-deficient baculovirus-infected cells. We suggest
      that hemin prevents the conversion of an inactive p67-DG into an active form
      possibly by covalent modification such as protein phosphorylation or protein
      glycosylation. The active form is more efficiently recognized by the p67-DG
      antibodies since these antibodies were prepared against the active form of p67
      DG.

PMID- 9186502
TI  - The major 20-kDa polysaccharide of Staphylococcus epidermidis extracellular slime
      and its antibodies as powerful agents for detecting antibodies in blood serum and
      differentiating among slime-positive and -negative S. epidermidis and other
      staphylococci species.
AB  - Staphylococcus epidermidis has been recognized as an important pathogen in
      immunocompromised hosts and patients with prosthetic or implanted medical
      devices. A highly adhesive extracellular material (slime or biofilm) produced by
      certain strains is associated with bacterial adherence to and growth on
      biomaterials contributing to pathogenesis of bacteremia. We have recently
      reported on the isolation and characterization of a sulfated 20-kDa acidic
      polysaccharide which constitutes slime's major component. Immunization of rabbits
      with crude slime and 20-kDa polysaccharide gave rise to readily reactive sera
      without manipulation of the 20-kDa polysaccharide structure. Immunological
      studies using purified polyclonal antibodies to 20-kDa polysaccharide by direct
      and competitive ELISA showed that they exhibit a high degree of reactivity and
      specificity with the homologous antigen. A significant proportion of the
      reactivity of antibodies to crude slime was also shown to be attributed to the 20
      kDa polysaccharide. This polysaccharide is immunogenic in humans since blood sera
      derived from patients 10-15 days after confirmation of slime-producing S.
      epidermidis bacteremia gave approximately 16 times higher reactivity than that of
      healthy individuals. Antibodies to 20-kDa polysaccharide were able to recognize
      and react specifically with slime-positive S. epidermidis strains compared to
      slime-negative ones (2 to 5 times higher reactivity). Moreover, these antibodies
      exhibited statistically significant (P < 0.05) differences in the degree of
      reactivity among S. epidermidis and other staphylococci species. These results
      open a new area in the diagnosis of S. epidermidis infection by direct analysis
      in blood sera, in differentiating among slime-positive and slime-negative strains
      as well as in distinguishing slime-producing S. epidermidis from other
      staphylococci species by simple laboratory tests.

PMID- 9186501
TI  - Calpain contributes to silica-induced I kappa B-alpha degradation and nuclear
      factor-kappa B activation.
AB  - Both silica and lipopolysaccharide (LPS) induce a rapid degradation of I kappa B
      alpha, an intracellular inhibitor of the nuclear factor (NF)-kappa B
      transcription factor. In this report, we demonstrate that MG132, a relatively
      specific proteasome inhibitor, is capable of suppressing LPS-induced I kappa B
      alpha degradation and NF-kappa B activation in mouse macrophage line RAW 264.7
      cells, but is unable to influence the same induction produced by silica. In
      contrast, the lysosome inhibitor chloroquine has little effect on I kappa B alpha
      degradation induced by either silica or LPS. In fact, chloroquine enhances the
      signal-induced nuclear expression of NF-kappa B p50/p65 heterodimer by inhibiting
      the resynthesis of I kappa B alpha. With the use of transient transfection of a
      plasmid that expresses calpastatin, a natural inhibitor for calpain, the silica
      induced degradation of I kappa B alpha and NF-kappa B activation was attenuated.
      In contrast, no inhibition of LPS-induced I kappa B alpha degradation and NF
      kappa B activation was observed by the overexpression of calpastatin. This
      suggests that calpain contributes to silica-induced I kappa B alpha degradation
      and NF-kappa B activation but not to LPS-induced I kappa B alpha degradation and
      NF-kappa B activation.

PMID- 9186503
TI  - Novel strategies for eutherian x marsupial somatic cell hybrids: mapping the
      genome of Monodelphis domestica.
AB  - Two hundred thirty-seven independent somatic cell hybrids have been obtained
      between opossum (Monodelphis domestica) splenocytes, bone marrow cells, or
      primary fibroblasts, and HPRT-deficient or TK-deficient Chinese hamster, mouse,
      American mink, or common vole fibroblast lines. Because extreme segregation and
      fragmentation of marsupial chromosomes commonly occurs in eutherian x marsupial
      somatic cells hybrids, we developed a rapid primary screening method that enables
      the identification of primary clones containing a large amount of opossum DNA 20
      25 d after fusion. This method, which depends on in situ hybridization of biotin
      labeled total opossum DNA on interphase nuclei of hybrid cells fixed on the
      bottom of microwell plates, was used to screen the 237 hybrid clones; 52 of them
      had a substantial amount of opossum DNA. G-banding and in situ hybridization of
      biotin-labeled total opossum DNA on metaphase spreads of the clones enabled
      identification of 17 hybrid clones containing from two to seven intact
      chromosomes of M. domestica on the background of Chinese hamster or vole
      chromosomes. The hybrid clones with intact opossum chromosomes are used in a
      panel constructed for mapping the opossum genome. Initial mapping results from
      these clones have led to the tentative assignment of GPI and GOT1 to chromosome
      1; 6PGD to chromosome 4; LDHA to chromosome 5; LDHB to chromosome 8; and PGK and
      G6PD to the X chromosome. On the basis of indirect evidence we also tentatively
      assigned HPRT to the X chromosome and TK to chromosome 5 of M. domestica. These
      are the first tentative chromosomal assignments by any technique for this
      species.

PMID- 9186504
TI  - Hypomethylation of human sperm pronuclear chromosomes.
AB  - Using the methylase SssI enzyme, we have analyzed the degree of in situ
      methylation of human sperm pronuclear chromosomes obtained by fertilizing hamster
      oocytes with human sperm. Untreated (control) sperm chromosome complements showed
      a higher degree of in situ methylation, compared to sperm complements previously
      treated with 5-azadeoxycytidine or lymphocyte chromosomes. This indicates that
      human sperm pronuclear chromosomes have a lower degree of genomic methylation
      compared to that of other somatic cells. The similarity in the degree of in situ
      methylation of the euchromatic and heterochromatic regions of chromosomes 1, 9,
      15, and 16 and the Y chromosome in human sperm does not support the existence of
      a possible correlation between hypomethylation and heterochromatin
      decondensation.

PMID- 9186505
TI  - AZT induces high frequency, rapid amplification of centromeric DNA.
AB  - The reverse transcriptase inhibitor 3'-azido-deoxythymidine (AZT) has previously
      been shown to be incorporated into specific regions near the telomeres and
      centromeres of Chinese hamster ovary cell chromosomes. Our investigation of the
      effects of AZT on chromosome stability has led to the discovery of a high
      frequency amplification of telomere-like centromeric DNA. The amplified
      structures, when analyzed cytogenetically, appear as tandem arrays of tightly
      clustered blocks of centromeric repeats containing telomeric sequences (TTAGGG)n.
      There were 5-13 blocks of amplified DNA per structure. These structures form
      rapidly within one or two cell cycles and can be observed with an incidence as
      high as 2%. Because the amplification was so rapid, we tested whether the
      amplification structures could be the result of aberrant overreplication by
      analyzing BrdU incorporation. Our results indicate that the amplified DNA does
      not undergo abnormal replication during its formation, but appears to form from
      existing centromeric regions. We propose a model that involves the excision of
      multiple centromeric DNA regions from other chromosomes and their relocalization
      to a new site.

PMID- 9186506
TI  - Increased aneuploid frequency in spermatozoa from a Hodgkin's disease patient
      after chemotherapy and radiotherapy.
AB  - The frequency of sperm aneuploidy was investigated by fluorescence in situ
      hybridization (FISH) in a Hodgkin's disease patient shortly after he had received
      chemotherapy and radiotherapy. Sperm karyotyping of the same patient had
      previously shown multiple structural abnormalities in most spermatozoa
      immediately after radiotherapy (day 0), whereas most spermatozoa collected 5 wk
      later (day 38) exhibited normal metaphase divisions (Rousseaux et al., 1993).
      Variations in the frequency of aneuploidy could not be detected by sperm
      karyotyping. Multicolor FISH on interphase spermatozoa revealed an increase in
      the rate of disomy for chromosomes 1, 6, 11, X, and Y at day 0 as well as at day
      38. The high frequency of 24,XY (nondisjunction at meiosis I) and 24,XX
      (nondisjunction at meiosis II) spermatozoa (8.46% and 1.64% at day 0,
      respectively) from the Hodgkin's disease patient suggests that both meiosis I and
      II are affected and that the X chromosome is frequently involved in such
      malsegregation events. The rate of 46,XY diploidy was also increased in the
      patient's sperm, up to 0.62% at day 0. While radiotherapy probably affected the
      postmeiotic cells (spermatids), the patient's cancer and/or chemotherapy are the
      two major factors that could have affected the dividing spermatogonia and/or
      spermatocytes, resulting in high aneuploidy rates.

PMID- 9186507
TI  - Genomic organization and mapping of the human HEP-COP gene (COPA) to 1q.
AB  - In eukaryotic cells, protein transport between the endoplasmic reticulum and
      Golgi compartments is mediated in part by non-clathrin-coated vesicular coat
      proteins (COP). Seven COP subunits have been recognized, and represent components
      of a complex known as coatomer. We have previously isolated the cDNA of the human
      homolog of alpha-COP, designated HEP-COP and given the official gene symbol COPA.
      Here we report the genomic organization of COPA, which contains 33 exons ranging
      in size from 67 to 611 bp. Mapped by PCR and cycle sequencing, all the exon
      intron junctions conformed with the GT-AG rule, the 32 introns ranging from about
      80 bp to 4 kbp, with the genomic DNA of COPA estimated to span approximately 37
      kb. Southern blot analysis of genomic DNAs of nine eukaryotic species, from human
      to yeast, revealed identical signals totaling 36 kb each for man and monkey only.
      Using 5' RACE and primer extension analysis, the putative transcriptional start
      site was localized to 466 nucleotides upstream of the translation initiation
      codon. Comprising a 126-nucleotide 5' untranscribed genomic sequence and a 466
      nucleotide 5' noncoding cDNA sequence, the 592-nucleotide 5' CpG island lacked
      TATA and CAAT boxes but displayed a high G+C content, was enriched for CpG
      dinucleotides, and contained a potential Sp1-binding site, i.e., features
      compatible with a housekeeping gene. COPA was mapped by fluorescence in situ
      hybridization to chromosome region 1q23-->q25.

PMID- 9186509
TI  - Robertsonian chromosomal rearrangements in the short-tailed shrew, Blarina
      carolinensis, in western Tennessee.
AB  - We report significant heterozygosity for numerous Robertsonian translocations in
      the southern short-tailed shrew (Blarina carolinensis) in western Tennessee.
      Eight Robertsonian rearrangements were documented using G-banding techniques that
      explain the variability in diploid numbers from 46 throughout most of the range
      of the species to 34-40 in western Tennessee. These fusions resulted in the loss
      of telomere sequences and were not associated with nucleolar organizer regions.
      When heterozygocity is considered, the lowest diploid number possibly present
      would be 30. Four localities with distances of over 180 km apart were sampled,
      and 80-90% of the collected animals were heterozygous for at least one
      rearrangement. No putative parental type was found in western Tennessee.
      Heterozygosity for the same rearrangements was found in these different
      localities, and no monobrachial fusions were noted. Thus, this is a very wide
      hybrid zone with rare or absent parental types in the areas sampled or is an
      evolutionary stage preceding establishment of Robertsonian races. Selective
      forces, if any, were minimal, as evidenced by the wide area of polymorphism,
      significant heterozygosity, and the fact that the Robertsonian translocations
      were in Hardy-Weinberg equilibrium. The origin of such extensive polymorphism in
      western Tennessee is discussed, especially in light of putative effects of the
      New Madrid seismic activity. Similarities and differences are noted between the
      Blarina model and the well-documented variation in the European common shrew
      (Sorex araneus) and Mus musculus groups.

PMID- 9186508
TI  - Chromosome assignment of 115 expressed sequence tags (ESTs) from human skeletal
      muscle.
AB  - The chromosome assignment of 115 expressed sequence tags (ESTs) from human
      skeletal muscle, 101 of which identify unknown human genes, is reported. The ESTs
      were selected among over 4,000 obtained from systematic sequencing of a skeletal
      muscle cDNA library containing 3' portions of the mRNAs. Chromosome assignments
      were obtained by PCR amplification of two panels of human x rodent somatic cell
      hybrids. Analysis of these preliminary data suggests a nonrandom distribution of
      muscle ESTs in the human chromosome complement. The unexpected occurrence of
      multiple chromosome localizations for some ESTs is discussed.

PMID- 9186510
TI  - Evolution of the black muntjac (Muntiacus crinifrons) karyotype revealed by
      comparative chromosome painting.
AB  - The black muntjac (Muntiacus crinifrons) has an unusual karyotype of 2n = 8 in
      females and 2n = 9 in males. We have studied the evolution of this karyotype by
      hybridising chromosome-specific paints derived from flow-sorted chromosomes of
      the Chinese muntjac (M. reevesi, 2n = 46) to chromosomes of the black muntjac.
      The hybridisation pattern allowed us to infer chromosomal homologies between
      these two species. Tandem and centromeric fusions, reciprocal translocations, and
      insertions are involved in the reduction of the diploid number from 2n = 46 to 2n
      = 8, 9. The painting patterns further show complex chromosomal rearrangements in
      the male black muntjac which involve more than half the karyotype, including both
      sex chromosomes. Since early meiosis is reported to be normal without any visible
      inversion loops of the synaptonemal complex, the observed chromosomal
      rearrangements would lead to heterosynapsis and, therefore, leave a large
      fraction of the male black muntjac karyotype balanced between the two sexes.

PMID- 9186511
TI  - The murine Ext1 gene shows a high level of sequence similarity with its human
      homologue and is part of a conserved linkage group on chromosome 15.
AB  - We have cloned and sequenced the murine homologue of the human EXT1 gene. At the
      protein level, these genes show almost complete identity as divergence is limited
      to only 5 amino acid positions that are scattered about the whole sequence. In
      addition, similarity searches identified a protein from chromosome III of C.
      elegans that shows significant similarity to the human and murine EXT/Ext genes.
      Using high resolution backcross mapping, the murine Ext1 was mapped at 26.55 cM
      between D15Mit143 and D15Mit153 on mouse chromosome 15. Therefore, Ext1 is part
      of an evolutionarily conserved linkage group including SDC2/Hspg1, TRHR/Trhr,
      EXT1/Ext1, MYC/Myc, and TG/Tgn.

PMID- 9186512
TI  - The spreading of metaphases is a slow process which leads to a stretching of
      chromosomes.
AB  - In routine chromosome harvesting of blood lymphocytes it is well accepted that
      metaphase spreads are obtained from fixed mitotic cells which burst on the
      surface of slides during the dropping procedure. For confirmation and
      clarification, fixed mitotic cells were dropped onto coverslips and observed
      under an inverted microscope during the evaporation of the fixative. Fixed
      mitotic cells in the metaphase stage first stick onto the surface of the
      coverslip without changing their three-dimensional shape and they do not burst.
      Thereafter, when evaporation of the fixative occurs, they slowly flatten until
      they are spread. This slow process leads to a stretching of chromosomes which may
      be a prerequisite for high resolution banding patterns. Confocal laser scanning
      microscopic measurements of the length, thickness, and width of chromosomes after
      (i) short term evaporation of the fixative, (ii) evaporation of the fixative
      under routine harvesting conditions and (iii) a prolonged evaporation, confirmed
      the stretching of chromosomes. The humidity, the temperature, and the drying time
      of the fixative influence the dynamic flow of the remaining fixative on the
      slide. This dynamic flow leads to an intensive wash of the fixed mitotic cells
      with increasing concentrations of acetic acid which is primarily responsible for
      the better quality of the metaphase spread.

PMID- 9186513
TI  - A somatic cell hybrid panel for distal 17q: GDIA1 maps to 17q25.3.
AB  - A somatic cell hybrid panel was constructed consisting of seven hybrids with
      translocation breakpoints spanning the region 17q23-->q25. Hybrid clones carrying
      the longarm derivative of chromosome 17 in the absence of the normal chromosome
      17 and of the derivative 17 were initially identified by PCR typing for a
      proximal and distal 17q marker. The translocation breakpoints of the hybrids were
      then mapped in more detail by PCR analysis for a number of microsatellite markers
      from chromosome 17q as well as for five gene loci (CACNLG, GH1, SOX9, TIMP2, TK1)
      previously mapped to the region 17q23-->q25. In addition, the locus for GDIA1 was
      mapped by FISH to 17q25.3 and fine mapped with the help of the hybrid panel.
      These seven new hybrids complement the existing somatic cell hybrid panel for the
      long arm of chromosome 17q.

PMID- 9186514
TI  - Cellular localization and chromosome mapping of a novel candidate tumor
      suppressor gene (ING1).
AB  - A novel gene called ING1 encoding a 33-kDa protein that is an inhibitor of cell
      growth and a candidate tumor suppressor has been recently isolated (Garkavtsev et
      al., 1996). Here we show, using indirect immunofluorescence, that the protein
      (p33ING1) is located in the nucleus, which is consistent with its proposed role
      as a growth regulator. In addition, we show that a genomic probe to human ING1
      localizes to chromosome 13 at q33-->q34 by fluorescence in situ hybridization.
      This candidate tumor suppressor gene is located near a chromosome region which
      has been reported to be a site for translocation and deletion in gastric cancers
      and head and neck squamous carcinomas.

PMID- 9186515
TI  - Assignment of holocarboxylase synthetase gene (HLCS) to human chromosome band
      21q22.1 and to mouse chromosome band 16C4 by in situ hybridization.

PMID- 9186516
TI  - Assignment of renal specific Na(+)-phosphate cotransporter gene Slc17a1 to mouse
      chromosome bands 13A3-->A4 by in situ hybridization.

PMID- 9186517
TI  - Assignment of interferon gamma receptor (IFNGR1) to human chromosome bands 6q24.1
      ->q24.2 by in situ hybridization.

PMID- 9186518
TI  - Assignment of FGF13 to human chromosome band Xq21 by in situ hybridization.

PMID- 9186519
TI  - Assignment of Fgf12 to mouse chromosome bands 16B1-->B3 by in situ hybridization.

PMID- 9186521
TI  - The origin of human chromosome 18 from a human/ape ancestor.
AB  - Karyotype analysis by previous investigators demonstrated that human chromosome
      18 differs from homologous chromosomes in the great apes by a pericentric
      inversion. The present study uses fluorescence in situ hybridization on human and
      pygmy chimpanzee chromosomes to confirm the inversion and to delimit the regions
      where the breakpoints must have occurred in the human/ape ancestor.

PMID- 9186520
TI  - Assignment of Indian hedgehog (IHH) to human chromosome bands 2q33-->q35 by in
      situ hybridization.

PMID- 9186522
TI  - Incidence of chromosome 1 disomy in human sperm estimated by the primed in situ
      (PRINS) labeling technique.
AB  - The primed in situ (PRINS) labeling technique was used to determine the rate of
      disomy of chromosomes 1 and 16 in sperm of two normal subjects. Two different but
      specific primers (alpha-satellite and satellite II) for chromosome 1 were used in
      parallel experiments to test the efficiency of PRINS labeling in sperm nuclei. A
      minimum of 10,000 sperm nuclei per chromosome primer was analyzed, leading to a
      total number of 41,651 scored spermatozoa. Similar rates of chromosome 1 disomy
      (mean values, 0.18% and 0.20%) were found in both donors when the alpha-satellite
      and satellite II primers were used, demonstrating the reliability of PRINS
      labeling on sperm nuclei. For chromosome 16, the disomy rate among the two donors
      ranged from 0.20% to 0.24%. This study confirms that PRINS provides a rapid and
      efficient method for in situ chromosomal screening of sperm nuclei.

PMID- 9186524
TI  - Generation of small insert genomic FISH probes with high signal intensity
      suitable for deletion mapping.
AB  - We have developed a method to generate FISH probes from small (2-4 kb)
      nonrepetitive genomic restriction fragments. The probes showed a high
      hybridization efficiency of up to 90% in metaphase cells from normal peripheral
      blood. With the use of these probes, homozygous as well as hemizygous 9p
      deletions were reliably identified in nine leukemia-derived cell lines.

PMID- 9186523
TI  - Preferential induction of chromosome 1 multibranched figures and whole-arm
      deletions in a human pro-B cell line treated with 5-azacytidine or 5
      azadeoxycytidine.
AB  - 5-Azacytidine (azaCR) causes genomic demethylation and decondensation of
      juxtacentromeric heterochromatin in chromosomes 1, 9, and 16. We determined the
      karyotypes of a pro-B cell line (FLEB14) treated with azaCR or its
      deoxynucleoside analog (azaCdR). About 80% of the induced rearrangements were in
      chromosome 1, and almost 90% of these involved its pericentromeric region.
      Multibranched figures with up to seven chromosome 1 arms, as well as whole-arm
      deletions of this chromosome, were the predominant anomalies, often with one
      normal homolog of chromosome 1 present. Isochromosomes 1 and fusions in the
      pericentromeric regions of chromosomes 1 and 16 or chromosomes 1 and 9 were also
      seen. The overlap of the spectrum of chromosomal rearrangements in azaCR- or
      azaCdR-treated FLEB14 cells and in mitogen-stimulated lymphocytes from patients
      with a rare genetic disease (ICF) associated with localized DNA hypomethylation
      supports the hypothesis that the DNA demethylating activity of azaCR is essential
      for the induction of these pericentromeric rearrangements. These studies may help
      elucidate the overrepresentation of chromosome 1 pericentromeric rearrangements
      in many types of cancer cells.

PMID- 9186525
TI  - Assignment of Mep 1a to mouse chromosome band 17C1-D1 by in situ hybridization.

PMID- 9186526
TI  - Pulsed-field gel electrophoresis and FISH mapping of chromosome 9q22: placement
      of a novel zinc finger gene within the NBCCS and ESS1 region.
AB  - Chromosome 9q22 is a gene-rich region to which several human disease loci have
      been mapped. Pulsed field gel electrophoresis (PFGE) and FISH were used to
      determine the order of and distance between 12 chromosome 9q22 markers flanked by
      D9S196 and D9S180. D9S780 and XPA were within 190 kb of each other and hybridized
      to the same 460-kb NotI fragment as D9S180. ZNF169, a novel kruppel-type gene,
      and D9S280 shared several PFGE fragments indicating that they are not more than
      300 kb apart. Interphase FISH showed that COL15A1 lies distal to the region
      bounded by D9S180 and D9S196 and that ZNF169 is adjacent to D9S196. Based on the
      restriction fragment lengths in this region and estimates from FISH, the distance
      from D9S180 to D9S196 is not less than 2 Mb.

PMID- 9186527
TI  - Loss of heterozygosity analysis in a human fibrosarcoma cell line.
AB  - Loss of heterozygosity (LOH) is an important event in tumor formation. We have
      used polymorphic microsatellite repeat markers to identify and characterize LOH
      in spontaneous mutants of a human cell line, MR12-1, that is heterozygous for the
      adenine phosphoribosyltransferase gene (APRT+/-) located on chromosome 16q24.3.
      Initially, clones without extensive LOH (which are likely derived as a
      consequence of intragenic point mutations) and clones with multilocus LOH (which
      are likely due to major chromosome alterations) were identified. Clones with
      major regions of LOH were further characterized by assaying additional
      informative microsatellite markers. Analysis of 20 spontaneously-arising,
      independent APRT-/- clones from MR12-1 demonstrated that nine of the mutants
      retained both copies of APRT and 11 had undergone multilocus genetic alterations.
      The nature of LOH in four of the latter clones has been examined in detail by
      karyotype and fluorescence in situ hybridization analysis (Shao et al., 1996).
      These data demonstrate that LOH of chromosome 16 may be due to mitotic
      recombination, interstitial or partial deletion, or to more complex mechanisms.
      LOH in these clones may be a consequence of events similar to those observed in
      many tumors.

PMID- 9186528
TI  - Assignment of thyroid hormone responsive SPOT 14 homolog (THRSP) to human
      chromosome 11 bands q13.5-->q14.1 by in situ hybridization.

PMID- 9186529
TI  - Subregional assignment of the proopiomelanocortin gene (POMC) to human chromosome
      band 2p23.3 by fluorescence in situ hybridization.

PMID- 9186530
TI  - Integration of 101 DNA markers across human Xp11 using a panel of somatic cell
      hybrids.
AB  - One hundred and one DNA markers previously assigned to the short arm of the human
      X chromosome were localized on a hybrid mapping panel consisting of ten radiation
      reduced, and four classical somatic cell hybrids. Of the 101 DNA markers, 16 are
      genes, two are pseudogenes, 13 are expressed sequence tags, 32 are simple tandem
      repeats (STRs), four are restriction fragment length polymorphisms, one is a
      variable number of tandem repeats, and 33 are sequence tagged sites (STSs). Three
      of these markers, two STSs and one STR, were generated from the products of an
      inter-Alu PCR library of a radiation-reduced hybrid containing Xp11.4-->p11.22 as
      its only human DNA content. A second STR was isolated from a region-specific
      cosmid containing the gene ZNF21. The 101 DNA markers fell into 22 bins based on
      their retention on the hybrids of this panel, which, in combination with YAC
      contig data, could be further resolved into 24 bins. This hybrid map of Xp11 has
      an average resolution of approximately 0.8 Mb.

PMID- 9186531
TI  - Assignment of the chicken MAX gene to chromosome 5p by fluorescence in situ
      hybridization.
AB  - It has been shown that the protein encoded by the MAX gene plays an important
      role in the physiological activity of Myc oncoproteins. In this study, we
      determined the chromosome location of the chicken MAX gene via fluorescence in
      situ hybridization. Hybridization of two biotinylated cloned fragments of 5.7 kb
      and 12.0 kb derived from the chicken MAX locus localized the gene to chromosome
      5p. It is the third gene marker to be assigned to this telocentric
      macrochromosome. Since the MAX sequence is highly conserved both at the
      nucleotide and at the amino acid level in a wide range of vertebrate species, our
      data may provide evidence for the existence of a segmental homology between human
      and chicken chromosomes.

PMID- 9186532
TI  - Venous thrombosis: factor V G1691A genotyping related to APC resistance as
      measured by 2 methods.
AB  - Blood samples were collected from consecutive unrelated patients with venous
      thrombosis. The patients originate from the middle part of Sweden. We
      investigated the presence of the reported point mutation at nt 1691 of factor V
      which renders the protein resistant to cleavage by activated protein C (APC).
      Thirty-seven per cent of the patients were heterozygote carriers, and 4.5% were
      homozygotes for a mutated factor V gene. In addition, resistance to coagulation
      induced by APC was measured, both by the conventional APTT assay and by a
      modified APTT assay which has been reported to have an increased resolution.
      Compared to a control group of healthy people, the mean value was significantly
      lower in the patient group. A strong correlation between low APC ratio and
      presence of the factor V mutation was found. By using the modified method, a
      complete resolution of carriers of the factor V mutation and people with normal
      factor V alleles was found. However, there was still an overlap between
      heterozygote carriers and people homozygous for the mutation. The modified method
      was also found useful in patients treated with warfarin. Among 40 healthy blood
      donors 7% were found to be heterozygous.

PMID- 9186534
TI  - Differences in cell lineage involvement between MDS-AML and de novo AML studied
      by fluorescence in situ hybridization in combination with morphology.
AB  - We have employed fluorescence in situ hybridization (FISH) in combination with
      standard morphology (MGG/FISH) to identify the clonal involvement of different
      bone marrow cell lineages in 20 AML patients (14 MDS-AML, 6 de novo AML). Even
      though the number of cells belonging to the abnormal clone varied between
      individual cases, the percentage of clonal blasts was similar in MDS-AML and de
      novo AML patients. The erythropoietic cells appeared to be part of the abnormal
      clone in 13 of 14 patients with MDS-AML, but only in 1 of 6 with de novo AML.
      Similarly, clonal granulocytes were detected in 13 of 14 patients with MDS-AML,
      compared to 2 of 6 with de novo AML. Lymphocytes consistently displayed normal,
      diploid karyotype. The results suggest that it is possible to distinguish between
      MDS-AML and de novo AML by the use of MGG/FISH; in de novo AML the abnormal
      chromosomal clone is generally confined to the immature myeloid cells, while in
      MDS-AML mature granulocytes and erythroid cells are of clonal origin. It is,
      however, not possible to conclude that MDS-AML is a "multipotent" type of
      leukaemia, since it cannot be ruled out that the chromosomally aberrant erythroid
      cells and granulocytes represent surviving cells from the original MDS clone.

PMID- 9186533
TI  - Outcome of a multicenter treatment program including autologous or allogeneic
      bone marrow transplantation for de novo acute myeloid leukemia.
AB  - The results of an intensive treatment program for patients 16-60 yr of age with
      de novo acute myeloid leukemia are presented. The patients were given
      conventional induction treatment with daunorubicin and cytarabine. Patients not
      entering complete remission (CR) after 1 course of daunorubicin/cytarabine were
      given 1 course of amsacrine/etoposide/cytarabine. Those entering complete
      remission received 3 consolidation courses using mitoxantrone, etoposide,
      amsacrine and cytarabine. One hundred and eighteen patients were enrolled.
      Complete remission was attained after 1-2 courses in 90 patients (76%). Another 6
      patients reached CR after 3-4 induction courses for a total CR rate of 81%. If
      feasible, patients were offered either allogeneic or unpurged autologous bone
      marrow transplantation. Twenty-four patients underwent allogeneic bone marrow
      transplantation; 15 in first remission, 8 in second remission, 1 in early
      relapse. Thirty patients below 56 yr of age underwent autologous bone marrow
      transplantation in first remission. The overall probability of survival at 4 yr
      was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35%
      for the whole cohort of patients; 52% for patients below 40 yr of age. Patients
      undergoing allogeneic or autologous bone marrow transplantation in first
      remission had an overall survival of 86% and 47%, respectively, while the
      probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr.
      The CR rate and long-term results of this intensive treatment program compare
      favorably with other recent studies using intensive consolidation with allogeneic
      or autologous bone marrow transplantation or high dose cytarabine.

PMID- 9186535
TI  - Quantification of loss of haemoglobin components from the circulating red blood
      cell in vivo.
AB  - Previous studies have shown that a considerable amount of haemoglobin is lost
      from the intact red cell during its lifespan. The aim of this study was to
      determine the relative contribution of all the haemoglobin components to this
      process. Therefore, the relative amount of haemoglobins A0, A2, F and the
      glycated haemoglobins were determined in 24 fractions of different cell age.
      These fractions were obtained by the combination of counterflow and density
      centrifugation. When the absolute amount of all haemoglobin components were
      calculated using the MCH-values of each fraction, it appeared that the mean red
      cell loss of haemoglobins A0, A2, F, an unknown X and "rest" comprised,
      respectively, 440, 23, 1, 4 and 1 amol per cell, while the mean gain of the
      glycated haemoglobins was 84 amol per cell. This resulted in a net loss of 385
      amol of haemoglobin per cell. One of the glycated haemoglobins (HbA1e2) turned
      out to be the product of further carbamylation. It was concluded that in the
      first half of the red cell lifespan HbA0 and HbA2 decreased by glycation and
      carbamylation and that in the second half some of the HbA0 and HbA2 but also some
      of the glycated and carbamylated haemoglobin components leave the red cell. The
      total loss amounted to about 20%.

PMID- 9186536
TI  - Recombinant human erythropoietin in the treatment of cancer-related anaemia.
AB  - The efficacy and safety of recombinant human erythropoietin (rhEPO) were tested
      when given subcutaneously (s.c.) in an escalating dose of 2000-10,000 units (U)
      daily in 60 patients with cancer-related anaemia (CRA). A positive response,
      defined as an increase in haemoglobin more than 2 g/dl and independence of blood
      transfusions was observed in 23 of 48 evaluable patients (48%) within a median of
      8 wk. In detail, rhEPO corrected anaemia in 11 of 14 patients (79%) with
      malignant lymphoma, in 8 of 15 patients (53%) with multiple myeloma and in 4 of
      10 patients (40%) with a solid tumour. The median dose of rhEPO in successful
      cases was 5000 U daily. Four patients with agnogenic myeloid metaplasia and 5
      with myelodysplastic disorder failed to respond to rhEPO. No patient had any
      severe side effects. Pretreatment serum erythropoietin levels appeared to be a
      weak predictor for response to rhEPO treatment. In conclusion, rhEPO seems to be
      safe and effective in correcting CRA in certain groups of patients.

PMID- 9186537
TI  - Human FLT3 ligand acts on myeloid as well as multipotential progenitors derived
      from purified CD34+ blood progenitors expressing different levels of c-kit
      protein.
AB  - We studied the effect of human flt3/flk2 ligand (FL) on the proliferation and
      differentiation of purified CD34+ blood progenitors which express different
      levels of c-kit protein in clonal cell culture in comparison with that of stem
      cell factor (SCF). FL alone did not support significant colony formation.
      However, FL significantly enhanced neutrophil colony (CFU-G) formation in the
      presence of granulocyte-colony stimulating factor (G-CSF) by peripheral blood
      (PB)-derived CD34+c-kit- cells which contained a large number of CFU-G. In
      addition, FL could synergistically increase the number of CFU-G supported by a
      combination of interleukin (IL)-3 and G-CSF, as did SCF. As we reported
      previously, SCF showed a significant burst-promoting activity (BPA). In contrast,
      FL did not exhibit any BPA on PB-derived CD34+c-kithigh cells in which erythroid
      burst (BFU-E) was highly enriched. However, FL could synergize with IL-3 or GM
      CSF in support of erythrocyte-containing mixed (E-Mix) colony by PB-derived
      CD34+c-kithigh or low cells in the presence of Epo. Replating of E-Mix colonies
      derived from CD34+c-kithigh cells supported by IL-3+Epo+SCF yielded more
      secondary colonies than those supported by IL-3+Epo or IL-3+Epo+FL. When PB
      derived CD34+c-kitlow cells which represent a more immature population than
      CD34+c-kithigh cells were used as the target, number of secondary colonies
      supported by IL-3+Epo, IL-3+Epo+SCF or IL-3+Epo+FL was comparable. However, the
      number of lineages expressed in the secondary culture was significantly larger in
      the primary culture containing IL-3+Epo+FL than in that containing IL-3+Epo.
      These results suggest that FL not only acts on neutrophilic progenitors, but also
      on more immature multipotential progenitors.

PMID- 9186538
TI  - Treatment of the anemia of aplastic anemia patients with recombinant human
      erythropoietin in combination with granulocyte colony-stimulating factor: a
      multicenter randomized controlled study. Multicenter Study Group.
AB  - A multicenter randomized controlled study was undertaken in order to determine
      whether epoetin beta (EPO) ameliorates the anemia in aplastic anemia (AA)
      patients treated with granulocyte colony-stimulating factor (G-CSF). Enrolled
      patients were randomized into 3 groups: group C receiving G-CSF alone as the
      control; group L receiving G-CSF and 200 IU/kg of EPO; group H receiving G-CSF
      and 400 IU/kg of EPO. Throughout the study, the dose and the administration
      interval of G-CSF were adjusted to maintain neutrophil counts between 1000 and
      5000 microliters EPO was administered subcutaneously for 12 wk as the first step
      in treatment and when favorable effects were observed over this period, treatment
      was continued for another 12 wk as the second step in treatment. Significant
      erythroid responses were defined as increases in untransfused hemoglobin values >
      1.0 g/dl or > 50% decreases in RBC transfusion requirements over the treatment
      period. Of 131 patients enrolled, 88 patients allocated to groups L and H were
      evaluated for toxicity to EPO and 110 were evaluated for erythroid responses.
      Four of the 31 patients (12.9%) in group C, 6 of the 41 patients (14.6%) of group
      L, and 14 of the 38 patients (36.8%) of group H showed erythroid responses in the
      first step in treatment. The erythroid responses of group H were significantly
      higher than those of the other 2 groups (p < 0.05). The significant effects of
      EPO were due to erythroid responses in non-severe AA. Responding patients were
      significantly different from non-responders with regard to disease severity,
      hemoglobin concentration, reticulocyte count, serum endogenous erythropoietin
      levels and serum transferrin receptors; non-severe AA patients were more likely
      to respond to EPO, and responding patients had lower serum EPO and higher
      hemoglobin concentration, reticulocyte count and serum transferrin receptors than
      non-responders. The response rate increased in the second step in treatment,
      suggesting that long-term treatment improved the efficacy of EPO. No serious side
      effects were observed. From these results, we conclude that EPO given in
      combination with G-CSF is a safe and effective alternative for the treatment of
      anemia of a subset of AA patients.

PMID- 9186539
TI  - Leucocyte and platelet-derived bioactive substances in stored blood: effect of
      prestorage leucocyte filtration.
AB  - Adverse reactions to transfusion of allogeneic blood may depend on content of
      leucocytes and platelets and on storage-time of the erythrocyte suspensions.
      Therefore, we studied the efficacy of prestorage leucocyte reduction by
      filtration on total content and extracellular accumulation of histamine,
      eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase
      (MPO), plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in
      samples obtained from 5 units of SAGM blood, 7 units of plasma-reduced whole
      blood and 6 units of whole-blood before and after filtration, respectively. In
      addition, we analysed supernatants from the same units after storage at +4
      degrees C for 0, 21 and 35 d, respectively. The filtration was performed at room
      temperature within 2-4 h after donation. The substances were analysed by ELISA
      and RIA methods and we also analysed the donor plasma levels of the same
      bioactive substances. The total content of histamine, ECP, EPX, and MPO were 10
      70-fold higher in all unfiltered erythrocyte products compared to donor plasma
      concentrations, while PAI-1 content was 15-20-fold higher only in plasma-reduced
      whole-blood and whole-blood. Prestorage leucocyte filtration significantly
      reduced the total histamine, ECP, EPX, MPO and PAI-1 content to levels similar to
      donor plasma levels in plasma-reduced whole-blood and whole-blood, while PAI-1
      was still low in filtered SAGM blood. In addition, the levels of extracellular
      bioactive substances at d 0 after donation and filtration were within the range
      of concentrations in donor plasma, and there was no time-dependent accumulation
      during storage for 35 d at +4 degrees C. IL-6 was not detected in either plasma
      or samples obtained from the blood bags. These results suggest prestorage
      leucocyte filtration to deplete leucocyte contents to levels, which prevent the
      previously shown time-dependent accumulation of leucocyte derived bioactive
      substances in various erythrocyte suspensions. In addition, the PAI-1 results
      suggest leucocyte filters to reduce the obligatory platelet content in whole
      blood products.

PMID- 9186540
TI  - The platelet proaggregating and potentiating effects of unfractionated heparin,
      low molecular weight heparin and heparinoid in intensive care patients and
      healthy controls.
AB  - Heparin binds to platelets and can cause platelet proaggregating and potentiating
      effects, possibly causing thrombocytopenia, particularly in patients in intensive
      care with hyperaggregable platelets. In this study we compared the platelet
      proaggregating and potentiating effects of unfractionated heparin (UH), 2 low
      molecular weight (LMW) heparins, enoxaparin and dalteparin, and a heparinoid,
      danaparoid sodium (orgaran), to platelets of an ICU patient population and a
      normal control group. In both populations UH caused platelet aggregation in a
      dose-dependent manner. This occurred in the therapeutic range of the drug, with
      as little as 0.5 U/ml UH. The LMW heparins caused less and the heparinoid least
      platelet aggregation. Generally, the aggregation observed in ICU patients was
      greater than in the normal population. The potentiating effects of the 4 drugs in
      association with physiological agonists was examined. Similar patterns of
      potentiation were observed in both populations, with UH causing significant
      enhancement of platelet aggregation, the LMW heparins intermediate and heparinoid
      least enhancement. There was substantial variability in the individuals'
      platelets' reactions to the drugs, in particular to UH. Our findings suggest that
      UH has the greatest effect, the low molecular weight heparins an intermediate
      effect and the heparinoid the least propensity to cause platelet activation.

PMID- 9186541
TI  - Severe central nervous adverse effect of intrathecal chemotherapy in a 16-yr-old
      patient with Burkitt's type lymphoma.

PMID- 9186542
TI  - Change in FAS antigen expression during differentiation of CD34-positive cells
      isolated from peripheral blood stem cell harvest samples.

PMID- 9186543
TI  - Early age at onset in multiple myeloma and aetiological considerations in Turkey.

PMID- 9186544
TI  - Effects of TNP-470, a potent angiogenesis inhibitor, on growth of hematopoietic
      progenitors.

PMID- 9186545
TI  - IgM auto-antibody thrombocytopenia simulating pseudothrombocytopenia.

PMID- 9186546
TI  - The lac-z reporter gene: a tool for in vitro studies of malignant glioma cell
      invasion.
AB  - A reporter gene (lac-z) was introduced into rat (BT4C) and human (D-54 MG)
      proliferating glioma cell lines by means of liposomal transfection. Lac-z
      transfected glioma cells were first cultured as multicellular spheroids and then
      confronted with fetal brain aggregates. After various intervals the lac-z
      reporter gene product, bacterial beta-galactosidase, was histochemically detected
      in the cocultures. beta-Galactosidase was only detected in the glioma cells which
      showed an intense blue staining, which made them easily distinguishable from
      fetal tissue. Both glioma cell lines showed a clear pattern of migration and
      increasing invasion with time as the tumor cells infiltrated and destroyed the
      brain aggregates. Spheroid growth curves showed no significant differences
      between transfected and nontransfected cell lines. Likewise, flow cytometry
      measurements revealed no significant changes in ploidy between transfected and
      nontransfected rat glioma cells. In comparison, a shift in ploidy was observed in
      the human glioma cells after lac-z transfection. Stable integration of the lac-z
      gene into tumor cells was verified by Southern blot analysis. The results
      indicate that transfection of the lac-z reporter gene into glioma cells lines
      does not affect their growth or invasion potential in vitro. The lac-z reporter
      gene can thus be exploited to facilitate visualization of single migrating tumor
      cells and quantification of tumor invasion in in vitro coculture systems.

PMID- 9186547
TI  - Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice.
AB  - The combined influence of alendronate, a bisphosphonate compound, and taxol on
      the establishment and growth of human PC-3 ML subclones injected intravenously
      via the tail vein in SCID mice was investigated. The pretreatment of SCID mice
      with alendronate (0.04-0.1 mg/kg twice weekly or 0.1 mg/kg weekly) partially
      blocked the establishment of bone metastases by human PC-3 ML cells and resulted
      in tumor formation in the peritoneum and other soft tissues. However, alendronate
      pretreatment of mice (0.1 mg/kg twice weekly or weekly) and dosing along with
      taxol (10-50 mg/kg/day, twice weekly, or weekly) blocked the growth of PC-3 ML
      tumors in the bone marrow and soft tissues in a statistically significant manner
      and improved survival rates significantly (p < 0.001) by 4-5 weeks. ELISAs and
      zymography of matrix metalloproteinase production in vitro and in vivo showed
      that alendronate and taxol alone partially inhibited metalloproteinase
      production, but that taxol in combination with alendronate totally blocked
      protease production and release. The combined activities of alendronate and taxol
      appeared to inhibit the establishment and growth of tumors in SCID mice, perhaps,
      in part, as a result of inhibition of protease production and release.

PMID- 9186548
TI  - Treatment with modified heparins inhibits experimental metastasis formation and
      leads, in some animals, to long-term survival.
AB  - Two chemically modified heparins with low anticoagulant activity were studied in
      terms of their antimetastatic activity in the B16-BL6 melanoma model. The two
      heparins were a very low molecular weight heparin (VLMW-H) and a low molecular
      weight heparin with 100% succinylation of desulfated N groups (Succ100-LMW-H).
      Both heparins, VLMW-H more so than Succ100-LMW-H, were highly effective in
      decreasing the number of lung metastasis on day 21 when administered once
      subcutaneously 10 min before intravenous injection of melanoma cells or 2
      times/week for 3 weeks. When the time of survival was measured, both heparins did
      not significantly prolong survival when administered once before injection of the
      tumor cells. When a repeated treatment schedule was adopted over 3 weeks, both
      heparins led to a slight, yet significant prolongation of survival. When the
      repeated treatment protocol was continued beyond 3 weeks, a highly significant
      prolongation of survival was observed with VLMW-H and there were some long-term
      survivors (20% for VLMW-H and 10% for Succ-LMW-H) that remained disease-free
      after discontinuation of therapy on day 90. The present results confirm and
      reinforce the concept that heparins with reduced anticoagulant activity may have
      interesting therapeutic applications in the prevention of tumor metastasis.

PMID- 9186549
TI  - Micrometastases to the axilla in breast cancer: their size and season of
      presentation.
AB  - In a series of 1,069 breast cancer patients there were no significant differences
      in the numbers of node-negative or node-positive cases undergoing operation in
      the two halves of the year. This held also for cases with nodal micrometastases
      (0.2 cm2 or less). There were two histological types. Their distribution
      according to season was similar. Using the mean tumour area those presenting in
      the first half of the year were smaller than the others (p < 0.001), and more
      cases were under 0.000 cm2 (p < 0.005). In these cases the tumour cells tended to
      be in the capsular lymphatics and subcapsular sinus. In keeping with their
      histology, deaths were also more frequent than with those presenting in the
      second half of the year, in which the micrometastases were larger and had usually
      infiltrated the nodal lymphoid tissue. Thus the metastatic process in the primary
      appears to be active in the first part of the year when the smallest of the
      micrometastases are found entering the nodes. This may be a reflection of the
      growth form of the primary.

PMID- 9186550
TI  - Membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2
      activation in primary human ovarian epithelial carcinoma cells.
AB  - Metastatic dissemination of epithelial ovarian carcinoma occurs primarily through
      exfoliation of cells from the primary tumor, with subsequent implantation,
      invasion, and growth throughout the organs within the peritoneal cavity. Previous
      studies have suggested a role for matrix metalloproteinases (MMPs), particularly
      MMP-2, in ovarian cancer invasion and metastasis. To characterize further the
      role of MMPs and their inhibitors in ovarian carcinoma, in this study the
      production and activation of MMPs by short-term primary cultures of human ovarian
      epithelial carcinoma cells were analyzed. We report that MMP-2 is the predominant
      gelatinolytic MMP secreted by primary ovarian cancer cells derived from both
      ovarian tumors and ascites fluid. Furthermore, zymographic analysis demonstrated
      that MMP-2 is present in conditioned media in both the latent and activated
      forms, indicating that primary ovarian cancer cells catalyze proMMP-2 activation.
      Presence of a proMMP-2 activator was confirmed by immunohistochemistry and
      immunoprecipitation studies which found membrane-type 1 MMP (MT1-MMP) in the
      membranes of unstimulated cells and levels of both MT1-MMP and tissue inhibitor
      of metalloproteinases-2 (TIMP-2) were enhanced by culturing cells in the presence
      of concanavalin A. In addition, interaction of MMP-2 with the ovarian carcinoma
      cell surface resulted in a 2.5- to 5-fold increase in invasiveness. These data
      suggest that MT1-MMP-catalyzed activation of proMMP-2 may play a physiologic role
      in intraperitoneal invasion of ovarian carcinoma cells.

PMID- 9186551
TI  - Defective tumor vascularization induced by metastasin 1 expression.
AB  - It has been proposed that metastasin 1 (mts1), a member of the S100 Ca(2+)
      binding protein family, may play a role in tumor progression and metastasis. In
      order to test this possibility, we have performed gene transfer experiments using
      a human sense mts1 expression vector and human MCF7 malignant epithelial cells
      which do not express endogenous mts1. In vitro, mts1 expression did not modify
      proliferative or invasive properties of transfected MCF7 cells. In vivo, MCF7
      cells expressing mts1 were associated with tumors exhibiting necrosis, and
      abundant fibrous and poorly cellular stroma. Immunohistochemical staining of
      endothelial cells showed that, in the presence of mts1, the number and the size
      of tumoral microvessels were decreased and some of them were collapsed. No
      metastases were observed in mice with either mts1-expressing or nonexpressing
      tumors. In summary, these results indicate that (i) in vitro and in vivo, mts1
      does not confer invasive properties to MCF7 cells, and (ii) mts1 expression by
      MCF7 cells leads to defective tumor microvessels, leading to the hypothesis that
      mts1 may have a negative effect on neoangiogenesis and/or on the maintenance of
      blood vessels.

PMID- 9186552
TI  - SNA-8073-B, a new isotetracenone antibiotic inhibits prolyl endopeptidase. I.
      Fermentation, isolation and biological properties.
AB  - SNA-8073-B, an inhibitor of prolyl endopeptidase isolated from the broth filtrate
      of Streptomyces sp. SNA-8073, is a new isotetracenone antibiotic. It was purified
      by ethyl acetate extraction, silica gel column chromatography and high
      performance liquid chromatography on ODS column. SNA-8073-B has the molecular
      formula of C20H16O5 and is a stereoisomer of SNA-8073-A (fujianmycin B,
      rubiginone A2). SNA-8073-B inhibited prolyl endopeptidase of Flavobacterium non
      competitively (IC50 = 8.9 microM) when Z-Gly-Pro-pNA was used as a substrate, but
      SNA-8073-A did not show any inhibition even at 60 microM.

PMID- 9186553
TI  - A new anthracycline antibiotic, IT-62-B, converts the morphology of ras
      transformed cells back to normal: taxonomy, fermentation, isolation, structure
      elucidation and biological characterization.
AB  - A new antibiotic, IT-62-B was isolated from the culture broth of Streptomyces sp.
      IT-62 by extraction with acetone and then with ethyl acetate, followed by
      conventional column chromatography using silica gel, Sephadex LH-20 and silica
      ODS. Its structure (C39H47NO15, MW 769) was determined by 1H, 13C NMR, MS, IR and
      UV spectrometric techniques to be a new member of the baumycin-group
      anthracyclines. It showed moderate activity against Gram-positive bacteria and
      had antitumor activity against various tumor cell lines. Further, antibiotic IT
      62-B converted the morphology of ras-transformed NIH3T3 cells and T-cells back to
      normal at concentrations inhibiting cell growth by 30% or more.

PMID- 9186554
TI  - PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by
      Penicillium oblatum. I. Taxonomy of producing strain, fermentation, isolation and
      biological activities.
AB  - Three new nonsteroidal progesterone receptor ligands, PF1092A, B and C, have been
      isolated from Penicillium oblatum. They were purified from the solid cultures of
      rice media using ethyl acetate extraction, silica gel and Sephadex LH-20 column
      chromatographies, and crystallization. All three ligands competitively inhibited
      [3H]-progesterone binding to porcine uteri cytosol preparations with IC50 of 3.0
      x 10 nM (PF1092A), 2.2 x 10(2) nM (PF1092B) and 2.2 x 10(3) nM (PF1092C).

PMID- 9186555
TI  - PF1092A, B and C, new nonsteroidal progesterone receptor ligands produced by
      Penicillium oblatum. II. Physico-chemical properties and structure elucidation.
AB  - The structures of PF1092A (1), B (2) and C (3), new nonsteroidal progesterone
      receptor ligands produced by Penicillium oblatum, were elucidated by
      spectroscopic analyses. These compounds possess an eremophilane-type
      sesquiterpene carbon skeleton and differ only in that 1 and 2 are different
      monoacetates of 3. The absolute configurations of 1-3 were determined by single
      crystal X-ray diffraction analysis of the 4-bromobenzoyl ester of PF1092A and by
      measuring the optical rotations of the acetylation products of these compounds.

PMID- 9186556
TI  - NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus
      sp. NF 00659. I. Taxonomy, fermentation, isolation and biological activities.
AB  - Five novel cytotoxic antibiotics, NF00659A1 (1), A2 (2), A3 (3), B1 (4) and B2
      (5) were discovered. They were isolated from a culture mycelium of Aspergillus
      sp. These compounds were proved to have 4,5-seco-tricyclic diterpene alpha-pyrone
      structure by spectroscopic analyses. They showed potent antitumor activities
      against human ovarian carcinoma A2780 and human colorectal adenocarcinoma SW480
      cells, but did not show any antimicrobial activities at 1,000 micrograms/ml
      against Gram-positive and Gram-negative bacteria, yeasts and fungi.

PMID- 9186557
TI  - NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus
      sp. NF 00659. II. Structural elucidation.
AB  - NF00659A1, A2, A3, B1 and B2, having insecticidal and antitumor activities, were
      isolated from a culture mycelium of Aspergillus sp. NF 00659. The novel structure
      of NF00659s were determined mainly by spectroscopic studies including various NMR
      measurements. NF00659s have a common structure which consists of acyl, alpha
      pyrone and 4,5-seco-tricyclic diterpene moieties.

PMID- 9186558
TI  - Pterulinic acid and pterulone, two novel inhibitors of NADH:ubiquinone
      oxidoreductase (complex I) produced by a Pterula species. I. Production,
      isolation and biological activities.
AB  - Pterulinic acid (1) and pterulone (2), two novel halogenated antibiotics, were
      isolated from fermentations of Pterula sp. 82168. Both compounds exhibited
      significant antifungal and weak or no cytotoxic activities. 1 and 2 are effective
      inhibitors of eucaryotic respiration. The target of the antibiotics resides
      within the mitochondrial NADH:ubiquinone oxidoreductase (complex I).

PMID- 9186559
TI  - Pterulinic acid and pterulone, two novel inhibitors of NADH:ubiquinone
      oxidoreductase (complex I) produced by a Pterula species. II. Physico-chemical
      properties and structure elucidation.
AB  - The structures of two novel fungal antibiotics, isolated from a Pterula species,
      that interfere with the NADH:ubiquinone oxidoreductase and inhibit the
      respiration of eucaryotes, were determined by spectroscopic techniques. Both
      compounds, pterulinic acid (1a) and pterulone (2), contain a 1-benzoxepin ring
      system and are chlorinated. Pterulinic acid (1a), which was obtained as a 1:5
      inseparable mixture of the two isomers (Z)-1a and (E)-1a, in addition contains a
      furan. Their structures were determined by mass spectrometry and NMR
      spectroscopy, and 2D heteronuclear correlation experiments permitted the
      assignment of all NMR signals.

PMID- 9186560
TI  - Antimicrobial activity of viridiofungins.
AB  - A family of aminoacyl alkyl citrate compounds called viridiofungins, are novel
      squalene synthase inhibitors. The compounds have broad spectrum fungicidal
      activity but lack antibacterial activity. Although the compounds inhibit squalene
      synthase, the first committed step in ergosterol biosynthesis, results presented
      in this paper show that inhibition of fungal growth is not related to inhibition
      of ergosterol synthesis.

PMID- 9186561
TI  - Viridiofungins, novel inhibitors of sphingolipid synthesis.
AB  - Viridiofungins are broad spectrum antifungal agents that inhibit the squalene
      synthase in vitro, but do not specifically inhibit fungal ergosterol synthesis in
      whole cells, indicating a different mode of action for antifungal activity. In
      this report, we show that viridiofungins are potent in vitro inhibitors of serine
      palmitoyltransferase, the first committed enzyme in sphingolipid biosynthesis,
      and their antifungal activity is due to inhibition of sphingolipid synthesis.
      Additional related components with the same mode of action were isolated from the
      producing culture, Trichoderma viride, and inhibition of the serine
      palmitoyltransferase and antifungal activity is presented.

PMID- 9186562
TI  - Antimicrobial activities of chemically modified thiazolyl peptide antibiotic MDL
      62,879 (GE2270A).
AB  - MDL 62,879 (GE2270A) 1 is a new inhibitor of elongation factor-Tu (EF-Tu) and
      belongs to the class of thiazolyl peptide antibiotics. Controlled acid hydrolysis
      of 1 followed by treatment with base resulted in the lost of the two terminal
      amino acids and in the formation of water-soluble MDL 62,935 2. Although less
      active in vitro than its parent compound, 2 was able to inhibit by 50% an
      Escherichia coli cell-free protein synthesis system at roughly the same
      concentration of 1. MDL 62,935 2 was subjected to further modification at the
      beta-phenylserine residue. Derivatives obtained from 2 were less active in both
      antimicrobial (MIC) and enzymatic (IC50) assays. This suggests that beta
      phenylserine plays an important role for the inhibition of EF-Tu by 1 and 2.

PMID- 9186563
TI  - SYN-1012: a new beta-lactamase inhibitor of penem skeleton.
AB  - A new beta-lactamase inhibitor, SYN-1012, with a penem skeleton was synthesized
      and its biological activity compared with clavulanic acid, sulbactam, tazobactam
      and BRL-42715. The beta-lactamase inhibitory activity of SYN-1012 was comparable
      to BRL-42715. Clavulanate and penam sulphones (sulbactam and tazobactam) were
      more active against TEM-1 and OXA-1, but were less active against TEM-3 and
      cephalosporinase (Case) than SYN-1012. In combination with piperacillin, SYN-1012
      exhibited comparable or slightly lower synergistic effects than BRL-42715 against
      all the Gram-positive and Gram-negative isolates tested with only exception of
      Pseudomonas aeruginosa. The separate combinations of SYN-1012 and BRL-42715 with
      ceftazidime and cefotaxime provided comparable results against Gram-negatives,
      but not against Gram-positive isolates. Tazobactam was inferior to SYN-1012 in
      all cases. In comparison to tazobactam, SYN-1012 and BRL-42715 were relatively
      unstable in human and mouse plasma, and in mouse liver and kidney homogenates.
      Serum level of SYN-1012 and BRL-42715 after an intravenous administration of 20
      mg/kg in rabbit was undetectable after 1 hour.

PMID- 9186564
TI  - Gelastatins A and B, new inhibitors of gelatinase A from Westerdykella multispora
      F50733.

PMID- 9186565
TI  - Synthesis of (+/-)-PF1092A, B, and C; new nonsteroidal progesterone receptor
      ligands.

PMID- 9186566
TI  - Structures of two remarkable dimerization products of sarkomycin.

PMID- 9186567
TI  - Cladinose analogues of sixteen-membered macrolide antibiotics. V. Preparation of
      unsubstituted L-cladinose analogues: effect of methylation of a 3"-hydroxyl group
      on the bioactivity.

PMID- 9186568
TI  - Cytotrienin A, a novel apoptosis inducer in human leukemia HL-60 cells.

PMID- 9186569
TI  - Selenium salts and chromosome damage.
AB  - Sodium selenite and sodium selenate, fed by gavaging to age-matched male Swiss
      albino mice and observed after 24 h following a colchicine-fixative-air drying
      Giemsa schedule, were found to induce chromosome breaks and spindle disturbances
      in bone marrow cells. The four concentrations used were fractions of LD50 and the
      effects were directly proportionate to the concentration of the chemical. Sodium
      selenite induced a slightly higher frequency of chromosomal aberrations than
      sodium selenate.

PMID- 9186570
TI  - In vivo studies on genotoxicity of pure and commercial linuron.
AB  - The ureic herbicide linuron [3-(3, 4-dichlorophenyl)-1-methoxy-1-methylurea] (CAS
      330-55-2) was investigated for genotoxicity in a series of in vivo experiments.
      Since human exposure to herbicides is not only to the active principles, but also
      to all the chemicals present in the commercial formulation, we tested both pure
      and commercial linuron. Groups of rats were treated with gavage containing
      different doses of the herbicide (pure compound or commercial formulation) for 14
      days. The doses were 150, 300 and 450 mg/kg b.wt. for the pure compound and
      315.8, 631.6 and 947.4 mg/kg b.wt. for the commercial formulation (47.5% of
      linuron). Faeces and urine were collected at regular intervals. Urine specimens
      were analysed for their mutagenic metabolites, thioethers and D-glucaric acid
      content. Faeces extracts were tested for mutagenicity. Linuron's ability to cause
      DNA damage and cytogenetic effects was also investigated after treating groups of
      rats once with different doses of pure or commercial linuron. DNA single-strand
      breaks were assessed in rat liver using the alkaline elution technique and the
      single-cell microgel electrophoresis assay (SCGE: 'comet' assay), and in rat
      testes cells with the SCGE assay. Micronuclei induction was analysed in rat bone
      marrow erythrocytes. Results obtained were mainly negative when the excretion of
      mutagenic metabolites in urine and faeces of animals treated with the pure
      compound or with the linuron-based commercial formulation were monitored, whereas
      an increase in the urinary excretion of thioethers and D-glucaric acid was
      observed in rats treated with the commercial formulation. No increase in the
      frequency of micronucleated polychromatic erythrocytes was observed in the
      treated animals. However, linuron affected the viability of hepatocytes isolated
      from animals treated with higher doses. This cytotoxicity was accompanied by the
      induction of DNA single-strand breaks in the liver, as seen by the alkaline
      elution assay. The potential of pure linuron to induce in vivo DNA damage was
      confirmed with the microgel-electrophoresis technique ('comet' assay).
      Cytotoxicity was also seen in rat testes cells. However, no indication of DNA
      damage was visible.

PMID- 9186571
TI  - Genotoxicity and mitochondrial damage in human lymphocytic cells chronically
      exposed to 3'-azido-2',3'-dideoxythymidine.
AB  - AZT (3'-azido-2',3'-dideoxythymidine), the first nucleoside analog approved for
      the treatment of AIDS (acquired immunodeficiency syndrome), induces significant
      toxic effects in humans exposed to therapeutic doses. As an inhibitor of the HIV
      1 (human immunodeficiency virus 1) reverse transcriptase, AZT blocks the
      incorporation of nucleotides into the host's newly synthesized DNA. Incorporation
      of AZT into mammalian DNA as well as specific localization of the drug into
      telomeric DNA, has been previously documented by immunohistochemistry. As with
      other nucleoside analogs, AZT has affinity for polymerase-gamma, the enzyme
      responsible for the replication of mitochondrial DNA. In order to examine the
      mechanisms of toxic events induced by long-term AZT exposure, human T-lymphocytic
      H9 cells were cultured with 25 microM AZT for 7 months. In the resulting H9-AZT
      cells, incorporation of AZT into DNA was demonstrated by radioimmunoassay and
      immunohistochemistry, chromosomal aberrations and micronuclei were scored and
      intracellular lipid distribution was determined. Two pmol of AZT per microgram of
      DNA were detected by radioimmunoassay in H9-AZT cells. Control cells showed
      negative values in the radioimmunoassay. Cytogenetic observations on H9-AZT cells
      showed an increase in chromosomal aberrations and nuclear fragmentation when
      compared with unexposed H9 cells. Electron microscopy revealed mitochondrial
      damage and an elevated accumulation of neutral intracellular lipid deposits
      probably as a consequence of a distortion in the beta-oxidation of fatty acids
      normally carried out by this organelle. The toxicities explored here suggest that
      the mechanisms of AZT induced cytotoxicity in bone marrow of the patients
      chronically exposed to the drug in vivo may involve both chromosomal and
      mitochondrial DNA damage.

PMID- 9186573
TI  - Correlation between the adaptive response and individual sensitivity to
      monoepoxybutene in in vitro experiments on human lymphocytes.
AB  - Individual variations in the susceptibility to mutagenic/carcinogenic chemicals
      depend on the activity of xenobiotic metabolizing enzymes and on DNA- and
      chromosome-damage repair systems. Monoepoxybutene (MEB) is a genotoxic metabolite
      of 1,3-butadiene (BD), which has been classified as a probable carcinogen in
      humans. The purpose of the present study was to investigate by in vitro
      experiments on human whole blood lymphocytes (WBL), whether an individual
      sensitivity to MEB correlates with the adaptive response to the tested agent. In
      the analyzed group, 8.3% of blood donors were relatively sensitive to MEB. The
      comparison of SCE induction in cultures pretreated and not pretreated with an
      adaptive dose (AD) of MEB showed, that there was an adaptive response to MEB. The
      adaptive response in the group of relatively sensitive donors was similar to that
      of the relatively resistant ones. This result suggests that individual
      sensitivity to the tested agent and adaptive response depend on different
      biological mechanisms.

PMID- 9186572
TI  - Activity of a nitroalkene derivative, 1-(5-bromofur-2-il)-2-bromo-2-nitroethene,
      in the Salmonella/microsome assay and the mouse bone marrow micronucleus test.
AB  - Mutagenicity of a substituted nitroalkene, 1-(5-bromofur-2-il)-2-bromo-2
      nitroethene (BNF) was tested in the Salmonella/microsome assay using the strains
      TA 98, TA 100 and TA 100NR (nitroreductase deficient). BNF was a direct mutagen
      in TA 98 and TA 100; the response was lowered when exogenous metabolic activation
      (S9) was used. A further decrease in mutagenicity was observed in strain TA
      100NR, as compared to the parental TA 100, which showed the involvement of
      nitroreduction in the overall response elicited by BNF. The micronucleus assay
      was carried out in Swiss male mice which were given a single i.p. dose of 10-20
      mg/kg of BNF dissolved in peanut oil, bone marrow being sampled 24 and 48 h
      later. The micronucleated polychromatic erythrocyte counts (MNPCE) showed a weak
      response in the dose range of 10-17.5 mg/kg at the second sampling (48 h) and a
      significant rise for 20 mg/kg at 24 and 48 h.

PMID- 9186574
TI  - Genotoxicity of six pesticides by Salmonella mutagenicity test and SOS
      chromotest.
AB  - Two in vitro tests (Ames test and SOS chromotest), one for bacterial mutagenicity
      and one for primary DNA damage, were assayed to determine the genotoxic activity
      of 6 pesticides (atrazine, captafol, Captan, chlorpyrifosmethyl, molinate and
      tetrachlorvinphos). Assays were carried out both in the absence and presence of
      S9 fractions of liver homogenate from rat (Sprague-Dawley) pretreated with
      Aroclor 1254. Captan and captafol were genotoxic on both the Ames test and the
      SOS chromotest. Comparisons with mutagenesis data in Salmonella indicated that
      the SOS assay detected as genotoxic the pesticides that were mutagenic on the
      Salmonella test. Non-genotoxic effects were not detected in vitro either in the
      Salmonella/microsome assay nor in the SOS chromotest when bacterial tester
      strains were exposed to atrazine, molinate, chlorpyrifosmethyl and
      tetrachlorvinphos in the absence or presence of S9 mix.

PMID- 9186575
TI  - Flow cytometric analysis of micronucleated reticulocytes in mouse bone marrow.
AB  - This laboratory has previously reported a flow cytometric procedure for
      quantitatively analyzing mouse peripheral blood reticulocytes for micronucleus
      content. The current study extends this line of investigation by evaluating
      whether these same flow cytometric scoring procedures can be applied to the
      analysis of mouse bone marrow samples. To validate the method, three groups of
      male BALB/c mice were treated with 100 mg/kg b.wt. methyl methanesulfonate. Bone
      marrow samples were collected 20, 40 or 60 h after administration. A set of 5
      untreated animals was included to provide an indication of spontaneous
      micronucleus frequencies. The cells were fixed with ultracold methanol, treated
      with ribonuclease, and labeled with anti-CD71 antibody (FITC conjugate) and
      propidium iodide. This fixing and labeling procedure resulted in the resolution
      of the micronucleated reticulocyte population and facilitated high-speed
      acquisition and enumeration via flow cytometry. The number of micronucleated
      reticulocytes was determined flow cytometrically by the analysis of 10,000 total
      reticulocytes per bone marrow sample. In addition to these automated
      measurements, slides stained with acridine orange were prepared and the number of
      micronuclei per 1000 reticulocytes was determined microscopically for each
      sample. The resulting data demonstrate that flow cytometry can effectively
      enumerate micronucleated reticulocytes in mouse bone marrow. The advantages
      associated with an objective, high throughput scoring methodology are also
      clearly indicated.

PMID- 9186576
TI  - An initial assessment of the genotoxic impact of the Sea Empress oil spill by the
      measurement of DNA adduct levels in the intertidal teleost Lipophrys pholis.
AB  - The Sea Empress oil spill resulted in the release of vast quantities of
      potentially genotoxic contaminants into the coastal environment of the county of
      Pembrokeshire (UK). We are at present attempting to determine the potential
      genotoxic impact of the incident upon the native marine species of the area. Here
      we describe the levels of DNA adducts in specimens of the intertidal teleost,
      Lipophrys pholis, exposed to extensive oil extensive oil contamination as an
      indication of exposure to potential genotoxins. We detected elevated levels of
      adducts in L. pholis specimens from an area that underwent heavy oil
      contamination as compared to specimens from a clean reference area devoid of oil
      contamination. These preliminary studies indicated that the oil contamination
      induced DNA adducts in the L. pholis specimens, which could potentially cause
      genetic damage in this native marine species. Further studies are now required to
      assess the full extent of the genotoxic impact of the oil spill upon the
      Pembrokeshire area's native marine life.

PMID- 9186577
TI  - Stimulated rapid expression in vitro for early detection of in vivo T-cell
      receptor mutations induced by radiation exposure.
AB  - The T-cell receptor (TCR) mutation assay for in vivo somatic mutations is a
      sensitive indicator of exposure to ionizing radiation. However, this assay cannot
      be immediately applied after radiation exposure because expression of a mutant
      phenotype may require as long as several months. In the present study, we
      eliminate this time lag by stimulating lymphocytes with a mitogen that can
      accelerate the turnover of TCR protein expression in T-cells. When lymphocytes
      obtained from healthy donors were irradiated with various doses of X-rays and
      cultured with human interleukin-2 after phytohemagglutinin (PHA) pulse
      stimulation, the mutant frequency (MF) of CD4+ T-cells increased dose dependently
      during the first 7 days, then decreased rapidly due to the growth disadvantage of
      mutant cells. This suggests that PHA stimulation can shorten the expression time
      of a mutant phenotype to within a week after radiation exposure. The relationship
      between radiation dose and TCR MF on the seventh day was best fitted by a linear
      quadratic dose-response model. We applied this improved TCR mutation assay to
      gynecological cancer patients who received 5 days of localized radiotherapy,
      totaling about 10 Gy. The in vivo TCR MF in the patients did not change within a
      week after radiotherapy, whereas the in vitro TCR MF of PHA-stimulated
      lymphocytes from the same patients significantly increased 7 days after
      initiating culture. The estimated mean radiation dose to the peripheral blood
      lymphocytes of the cancer patients was about 0.9 Gy, based on the in vitro linear
      quadratic dose-response curve. This estimated dose was close to that described in
      a previous report on unstable-type chromosome aberrations from cervical cancer
      patients after receiving the same course of radiotherapy. On the basis of these
      findings, we propose that the improved TCR mutation assay is a useful biological
      dosimeter for recent radiation exposure.

PMID- 9186578
TI  - Use of Salmonella typhimurium TA 98, YG 1024 and YG 1021 and deconjugating
      enzymes for evaluating the mutagenicity from smokers' urine.
AB  - Four smokers were chosen for their different smoking habits, and their declared
      cigarette consumption confirmed by urinary measurement of nicotine and its
      metabolites. The promutagenicity of their urine was evaluated by the Ames test,
      modified according to Kado et al. (Mutation Res., 31 (1983)25-32) after
      extraction on XAD2 Amberlite resin. The different Salmonella typhimurium strains
      TA 98, YG 1021 and YG 1024 were compared to determine the presence of amino
      aromatic compounds in the urine of smokers of blond and black tobacco. The strain
      YG 1024 shows higher mutagenicity than TA 98 for extracts from the smoker's urine
      and more particularly from black tobacco smokers. In addition, the pretreatment
      of urine by external enzymatic systems (beta-glucuronidase or arylsulfatase)
      reveals the presence in the urine of glucurono- and sulfoconjugated forms of
      promutagens, including amino aromatic compounds.

PMID- 9186579
TI  - Hemodynamics, endothelial gene expression, and atherogenesis.

PMID- 9186580
TI  - Fluid shear stress-mediated signal transduction: how do endothelial cells
      transduce mechanical force into biological responses?
AB  - We propose a model for signaling events induced by fluid shear stress that
      incorporates many of the features discussed in this paper (FIG. 4). First,
      heterotrimeric G-proteins, as well as a small G-proteins, are activated by flow.
      Indeed, a G protein appears to be required for ERK1/2 activation by flow because
      ERK1/2 activation is completely inhibited by GDP-beta S. Then, flow activates
      phospholipase C and generates IP3 and diacylglycerol (DG). IP3 releases Ca2+ from
      internal Ca2+ stores via IP3 receptor and DG activates PKC. Nollert and
      colleagues have shown that flow activates PLC and increases IP3. It is possible
      that several different PKC isozymes are activated by flow including both Ca(2+)
      dependent and Ca(2+)-independent isozymes. These different isozymes may have
      specific downstream substrates. For example, PKC-epsilon may be involved in
      activation of ERK1/2, while the PKC isozyme responsible for activation of JNK
      remains unknown. It is also possible that these PKC isozymes may be important in
      gene transcription events. For example, PKC-zeta has been suggested to be
      involved in NF-kappa B-mediated gene transcription. Longer term changes in
      endothelial cell morphology and structure are likely to involve separate kinases.
      Important candidates for these changes include members of the c-Src and FAK
      families. c-Src is now considered to be a component of the focal adhesion complex
      and regulate focal adhesion formation and/or cytoskeletal rearrangement.
      Recently, stretch, another mechanostress, has been shown to activate c-Src in
      fetal rat lung cells. It has been clarified that ERK1/2 and JNK are regulated by
      the small G-proteins, Ras and Rac/Cdc42H, respectively, and their effectors in
      parallel with each other. Rac and Rho are also thought to be involved in membrane
      ruffling and/or cytoskeletal rearrangement. Fluid shear stress causes stress
      fiber formation and focal adhesion rearrangement. Recent study by Malek and Izumo
      suggested the importance of microtubules in shear stress-induced morphological
      change and actin stress fiber formation. It is clear that the focal adhesion
      complex plays an important role in shear stress-induced signal and it is
      interesting to speculate that shear stress-induced signaling has cross-talk with
      signaling induced by integrins. As a general model we propose that the
      integration between the rapid events stimulated by shear stress and the longer
      term events is mediated by tyrosine kinases that serve to regulate these multiple
      signal transduction pathways.

PMID- 9186581
TI  - Involvement of selectins in atherogenesis: a primary or secondary event?

PMID- 9186582
TI  - Intercellular junctions in the endothelium and the control of vascular
      permeability.

PMID- 9186583
TI  - C-type natriuretic protein inhibits intimal thickening after vascular injury.

PMID- 9186584
TI  - Hyperhomocyst(e)inemia and atherothrombosis.

PMID- 9186585
TI  - Nitric oxide in the vasculature: physiology and pathophysiology.

PMID- 9186587
TI  - Is overamplification of the normal macrophage defensive role critical to lesion
      development?

PMID- 9186586
TI  - Induction of endothelial platelet-derived growth factor-B-chain and intercellular
      adhesion molecule-1 by lysophosphatidylcholine.
AB  - Lysophosphatidylcholine (lyso-PC) is a major phospholipid component of
      atherogenic lipoproteins. Lyso-PC has been shown to differentially upregulate the
      adhesion molecules, such as VCAM-1 and ICAM-1, as well as smooth muscle growth
      factors, such as PDGF-A, B chains and HB-EGF gene expression in various cultured
      endothelial cells. In this paper, we demonstrate increased expression of cell-
      and matrix-associated forms of PDGF-B protein elicited by lyso-PC and further
      characterized potential signal transduction mechanisms responsible for lyso-PC
      induced human umbilical vein endothelial cell. Cycloheximide inhibited PDGF-B but
      not ICAM-1 mRNA induction by lyso-PC, suggesting the dependence on de novo
      protein synthesis for PDGF-B, but not ICAM-1. A protein kinase C (PKC) inhibitor
      did not block lyso-PC-induced increases in PDGF-B or ICAM-1 mRNA. The elevated
      level of cAMP blocked both PDGF-B and ICAM-1 upregulation by lyso-PC. However
      cAMP-elevating agents did not suppress ICAM-1 upregulation by PMA. Taken
      together, PDGF-B and ICAM-1 gene induction by lyso-PC may involve different
      signaling mechanisms; however, both appear to be independent of PMA-regulatable
      PKC activation but are suppressed by increased levels of intracellular cAMP.

PMID- 9186588
TI  - The role of oxidized LDL in atherogenesis: immunological response and anti
      phospholipid antibodies.

PMID- 9186589
TI  - Glycated lipoprotein and atherosclerosis.

PMID- 9186590
TI  - Atherogenesis and advanced glycation: promotion, progression, and prevention.

PMID- 9186591
TI  - Signal transduction for PDGF-induced chemotaxis of vascular smooth muscle cells.

PMID- 9186592
TI  - Molecular determinants of atherosclerotic plaque vulnerability.

PMID- 9186593
TI  - Transgenic rabbit models for the study of atherosclerosis.

PMID- 9186594
TI  - Viral activation of coagulation: implications for thrombosis and atherosclerosis.

PMID- 9186595
TI  - The role of endothelin-1 in cardiovascular development.

PMID- 9186596
TI  - Cholesteryl ester transfer protein and atherogenesis.

PMID- 9186597
TI  - A new member with eleven binding repeats: novel insights into the LDL receptor
      gene family.

PMID- 9186598
TI  - Insights in vessel development and vascular disorders using targeted inactivation
      and transfer of vascular endothelial growth factor, the tissue factor receptor,
      and the plasminogen system.
AB  - VEGF has been proposed to participate in normal and pathological vessel
      formation. Surprisingly, lack of only a single VEGF allele resulted in embryonic
      lethality due to abnormal formation of intra- and extra-embryonic vessels.
      Homozygous VEGF-deficient embryos, generated by tetraploid aggregation, revealed
      an even more severe defect in vessel formation. These results (1) suggest a tight
      regulation of early vessel development by VEGF and, indirectly, the presence of
      other VEGF-like molecules; (2) reveal an unprecedented lethal phenotype
      associated with heterozygous deficiency of an autosomal gene, and (3) demonstrate
      that tetraploid aggregation was a valid and the only method to study the
      phenotype of the homozyogous VEGF-deficient embryos. The dominant and strict dose
      dependent role of VEGF in vivo renders this molecule a desirable therapeutic
      target for promoting or preventing angiogenesis. Tissue factor (TF) is the
      principal cellular initiator of coagulation and its deregulated expression has
      been related to thrombogenesis in sepsis, cancer, and inflammation. However, TF
      appears to be also involved in a variety of non-hemostatic functions including
      inflammation, cancer, brain function, immune response, and tumor-associated
      angiogenesis. Surprisingly, TF deficiency resulted in embryonic lethality due to
      abnormal extra-embryonic vessel development and defective vitelloembryonic
      circulation. The abnormal yolk sac vasculature is reminiscent of that observed in
      embryos lacking VEGF, possibly suggesting that both gene functions are
      interconnected. These targeting studies extend the recently documented role of TF
      in tumor-associated angiogenesis and warrant further study of its role in
      angiogenesis during other pathological disorders. The plasminogen system, via its
      triggers, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen
      activator (u-PA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1),
      has been implicated in thrombosis, arterial neointima formation, and
      atherosclerosis. Studies in mice with targeted gene inactivation of t-PA, u-PA,
      PAI-1, the urokinase receptor (u-PAR), and plasminogen (Plg) revealed (1) that
      deficiency of t-PA or u-PA increase the susceptibility to thrombosis associated
      with inflammation and that combined deficiency of t-PA:u-PA or deficiency of Plg
      induces severe spontaneous thrombosis; (2) that vascular injury-induced neointima
      formation is reduced in mice lacking u-PA-mediated plasmin proteolysis, unaltered
      in t-PA- or u-PAR-deficient mice and accelerated in PAI-1-deficient mice, but
      that it can be reverted by adenoviral PAI-1 gene transfer; and (3) that
      atherosclerosis in mice doubly deficient in apolipoprotein E (apoE) and PAI-1 is
      reduced after 10 weeks of cholesterol-rich diet. Thus, the plasminogen system
      significantly affects thrombosis, restenosis, and atherosclerosis.

PMID- 9186599
TI  - Human lesion studies.
AB  - We describe recent information on the atherothrombotic processes leading to the
      acute coronary syndromes (ACS) in humans. Then, we outline the mechanism of
      action and impact of lipid-lowering therapy in stabilization and secondary
      prevention of such processes. We start with (1) definitions of atherosclerotic
      lesions. In the progression of coronary atherosclerosis, eight morphologically
      different lesions are defined (Type I to VI) in various phases of disease. (2)
      Then we discuss vulnerable lipid-rich plaques and ACS. The type IV and Va lesions
      tend to be relatively small in size, but soft or vulnerable to disruption (with
      subsequent thrombosis) because of high lipid content (cholesterol esters rather
      than free cholesterol monohydrate crystals). The above process represents a
      "passive" phenomenon of plaque disruption. In addition to this "passive"
      phenomenon, an "active," macrophage-dependent, phenomenon of plaque disruption is
      evolving. (3) We then show the role of thrombosis in ACS. Monocytes/macrophages
      in lipid-rich plaques may play a detrimental role after plaque disruption,
      promoting thrombin generation and thrombosis through the tissue factor pathway,
      which can be prevented by tissue factor pathway inhibitor. Such thrombotic
      phenomena are critical in the development of ACS. (4) Finally, we discuss the
      effect of lipid-modifying strategies on the vulnerable lipid-rich plaques. When
      high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the
      liquid or sterified cholesterol, and also its hydrolysis into cholesterol
      crystals depositing in the vessel wall, predominate over the influx of LDL
      cholesterol. Consequently, there is a decrease in the softness of the plaque and
      so, presumably in the "passive" phenomenon of plaque disruption. When low HDL
      cholesterol is increased experimentally, there is a partial decrease in the
      number and activity of the macrophages and so, presumably in the "active"
      phenomenon of plaque disruption.

PMID- 9186600
TI  - The PDAY Study: natural history, risk factors, and pathobiology. Pathobiological
      Determinants of Atherosclerosis in Youth.

PMID- 9186601
TI  - Inhibition of neointimal formation by natural heparan sulfate proteoglycans of
      the arterial wall.

PMID- 9186602
TI  - Serial magnetic resonance imaging of experimental atherosclerosis allows
      visualization of lesion characteristics and lesion progression in vivo.

PMID- 9186603
TI  - Clinical trials to prevent restenosis after percutaneous coronary
      revascularization.

PMID- 9186604
TI  - In vivo gene transfer: a biological tool.

PMID- 9186605
TI  - Vascular gene transfer using smooth muscle cells.

PMID- 9186606
TI  - Prevention of restenosis by gene therapy.
AB  - We have developed an efficient vector system based on the liposome for the
      delivery of oligonucleotides and genes into various organs. The liposome was
      decorated with fusion proteins of HVJ (Sendai virus) to introduce DNA directly
      into the cytoplasm and contained DNA and DNA-binding nuclear protein inside the
      particle to enhance its expression. Using the vector, called HVJ-liposome gene
      delivery system, we attempted to prevent the neointima formation of vascular
      walls after balloon injury. Antisense oligonucleotides against PCNA and cdc2
      kinase transferred into injured arterial walls by protein-liposomes greatly
      reduced the message of those genes and inhibited neointima formation of the
      injured artery for 8 weeks. Moreover, double-stranded oligonucleotides containing
      the consensus sequence for E2F binding sites inhibited the growth of smooth
      muscle cells and prevented neointima formation. Finally, c-NOS gene was
      introduced into injured rat carotid artery by HVJ-liposome, and neointima
      formation was inhibited by 70% for 2-4 weeks.

PMID- 9186607
TI  - Atherosclerosis and angiogenesis. Its pathophysiological significance in humans
      as well as in an animal model induced by the gene transfer of vascular
      endothelial growth factor.

PMID- 9186608
TI  - Von Willebrand factor-dependent shear-induced platelet aggregation: basic
      mechanisms and clinical implications.

PMID- 9186609
TI  - Annexin II: a novel mediator of cell surface plasmin generation.

PMID- 9186610
TI  - Expression of fibrinolytic genes in tissues from human atherosclerotic aneurysms
      and from obese mice.
AB  - The disturbances in the balance of pro- and antifibrinolytic activity, as
      observed in AAA and obesity, respectively, have considerable potential for
      influencing both intra- and extravascular fibrinolytic events and may be causally
      related to the development of vascular disease. For example, the wall of the
      aortic atherosclerotic aneurysm seems to host an uneven distribution and
      imbalanced expression of the various components of the fibrinolytic system. The
      sites of increased proteolytic activity may contribute to localized
      neovascularization and promote the rapid breakdown of ECM components, which
      result in mural weakening and eventual rupture of untreated aortic aneurysms. On
      the other hand, the disturbance of the normal hemostatic balance observed in
      obesity appears to result from the elevated expression of PAI-1 by the adipose
      tissue. Our data strongly suggest that the adipocyte is one of the primary cells
      in the adipose tissue capable of expressing PAI-1 both in obesity, and in
      response to cytokines and hormones like TNF-alpha and insulin. Since both TNF
      alpha and insulin are known to increase in obesity, the elevated levels of PAI-1
      observed in the plasma of obese individuals may result from TNF-alpha and/or
      insulin induction of PAI-1 in the adipose tissue itself.

PMID- 9186611
TI  - Early mural reactions to fibrinogen injections into aortic wall of rabbits.

PMID- 9186612
TI  - Eicosapentaenoic acid and docosahexaenoic acid inhibit DNA synthesis through
      inhibiting cdk2 kinase in vascular smooth muscle cells.

PMID- 9186613
TI  - Role of the macrophage scavenger receptor for internalization of
      lysophosphatidylcholine in oxidized low density lipoprotein-induced macrophage
      growth.

PMID- 9186614
TI  - New assay for glycated lipoproteins by high-performance liquid chromatography.
AB  - We developed an automated analytic system for glycated lipoprotein using high
      performance liquid chromatography (HPLC) with an affinity boronate column and a
      gel permeation column. This system can measure glycated lipoprotein (glycated LDL
      and glycated HDL) in a small (5 microliters) sample of serum in a short time (40
      min/sample). Recovery with this system was 92.1%. Therefore a large number of
      samples can be measured in clinical use. The system should contribute to an
      elucidation of the role of glycated lipoprotein in atherosclerosis.

PMID- 9186615
TI  - Wild-type p53 gene transfer: a novel therapeutic strategy for neointimal
      hyperplasia after arterial injury.

PMID- 9186616
TI  - Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses
      neointimal formation in the balloon-injured rat carotid arteries in vivo.

PMID- 9186617
TI  - Difference in atherosclerosis between the populations of a fishing and a farming
      village in Japan.

PMID- 9186618
TI  - Arteriosclerotic lesions of the distal small coronary artery in cholesterol-fed
      rabbits differ from those in watanabe heritable-hyperlipidemic rabbits.

PMID- 9186619
TI  - An experimental induction of acute myocardial infarction and arterial thrombosis
      in rabbits.

PMID- 9186620
TI  - Thrombin activates NF-kappa B through thrombin receptor and results in
      proliferation of vascular smooth muscle cells: role of thrombin in
      atherosclerosis and restenosis.
AB  - We investigated the role of thrombin in the pathogenesis in atherosclerosis and
      restenosis. First we examined the effect of thrombin on cultured human vascular
      smooth muscle cells (VSMC). We showed that thrombin acts as a mitogen on VSMC
      through thrombin receptor. The expression of thrombin receptor was increased in
      the cell lines of VSMC established from directional coronary atherectomy (DCA).
      This is more pronounced in the cells from patients with restenosis after PTCA.
      Next we investigated the signaling pathway from thrombin/thrombin receptor.
      Thrombin activates thrombin receptor resulting in the exposing of the agonist
      peptide domain (thrombin receptor agonist peptide, TRAP). The signal from
      thrombin/thrombin receptor activated protein C kinase, tyrosine kinase, and MAP
      kinase and resulted in NF-kappa B activation. Furthermore, treatment of the cells
      with antisense p65 oligodeoxynucleotides of NF-kappa B inhibited the thrombin
      stimulated growth of VSMC in vitro. These results suggest that thrombin may have
      a role in the pathogenesis of atherosclerosis and restenosis after PTCA through
      the thrombin receptor.

PMID- 9186621
TI  - Contribution of adventitial myofibroblasts to vascular remodeling and lesion
      formation after experimental angioplasty in pig coronary arteries.

PMID- 9186622
TI  - Endothelial activation potentiates neointimal lesion formation in the rabbit
      aorta after balloon injury.

PMID- 9186623
TI  - Migration of medial smooth muscle cells to the intima after balloon injury.
AB  - Migration to the intima and other responses of M-SMC in the rat carotid artery
      and abdominal aorta after balloon injury were investigated in vivo. Migration
      occurred intensively between the second and fifth days after injury. About 80% of
      the cells were in the G1 and S phases of the cell cycle. The majority of the
      migrating cells were therefore simultaneously proliferating. Positive values of
      42.3%, 48.9%, 44.4%, and 32.8% of the migrating cells on the fifth day in the
      carotid artery for PDGF-B, elastase III B, MMP-I, and MMP-9, were observed,
      respectively. Many of the cells expressed messages of PDGF-A and elastases II and
      III B by in situ hybridization. Fine structures of the migrating cells were
      characterized as a synthetic phenotype of the smooth muscle cell with reduced
      attachment to their surrounding ECM. A biphasic proliferative response of the M
      SMC appeared on the second and fifth days. Migration occurred correspondingly in
      the proliferative period. The populations of M-SMC positive in immunostainings
      for PDGFs, their receptors, elastase III B, and MMP-1 and MMP-9 also increased
      biphasically, around 12 h and five days after the injury. The results of these
      studies suggest that the migrating cells were proliferative and synthesizing
      PDGFs, elastases, and collagenases.

PMID- 9186624
TI  - Regulation of neutral cholesterol esterase activity by cholesterol in J774 A.1
      macrophages.

PMID- 9186625
TI  - Remnant-like particles stimulate platelet aggregation in whole blood.

PMID- 9186626
TI  - Presence of apolipoprotein B-100 in human intestine epithelial cells.

PMID- 9186627
TI  - Novel roles for E-selectin in endothelial-leukocyte adhesion.

PMID- 9186628
TI  - Three putative integrin ligands identified in human aortic smooth muscle cells.

PMID- 9186629
TI  - Identification of dysfunctional endothelial cells over vascular lesions in the
      non-human primate.

PMID- 9186630
TI  - Role of T lymphocytes in the pathogenesis of atherosclerosis: animal studies
      using athymic nude rats.

PMID- 9186631
TI  - Lysophosphatidylcholine induces heparin-binding epidermal growth factor-like
      growth factor and interferon-gamma in human T-lymphocytes.

PMID- 9186632
TI  - Co-culture of platelets with activated J774.1 cells: effects on platelet
      aggregation and cyclic nucleotides.

PMID- 9186633
TI  - Significance of vascular natriuretic peptide system in vascular remodeling in
      humans and its application to gene therapy.

PMID- 9186634
TI  - Production of interleukin-6 induced by hypoxia linked to peripheral arterial
      disease.

PMID- 9186635
TI  - Autoantibodies and autoimmunity: a three-decade perspective. A tribute to Henry
      G. Kunkel.

PMID- 9186636
TI  - B lymphocyte developmental lineages.

PMID- 9186637
TI  - The role of autoreactivity in B cell selection.

PMID- 9186638
TI  - Effects of altered Bcl-2 expression on B lymphocyte selection.

PMID- 9186639
TI  - Balancing immunity, autoimmunity, and self-tolerance.

PMID- 9186640
TI  - Fas-dependent and Fas-independent mechanisms for selection of the mature human B
      cell repertoire.

PMID- 9186641
TI  - The roles of B cells in MRL/lpr murine lupus.

PMID- 9186643
TI  - In vivo consequences of B cell superantigen immunization.

PMID- 9186642
TI  - B lymphocytes as autoantigen-presenting cells in the amplification of
      autoimmunity.
AB  - The exact role of B cells in antigen presentation to naive T cells in vivo is
      presently not known. Here, we demonstrate the ability of a B cell subset
      consisting of B7-2pos-B cells to prime autoreactive T cells in B cell-deficient
      mice. In contrast, B cell-deficient mice are unable to mount a similar initiation
      and expansion of the autoimmune response. The expression of the B7-2
      costimulatory molecule as well as the specificity to a self-antigen, either
      murine cytochrome c or murine ribonucleoproteins (the target of autoimmunity in
      SLE), enabled B cells as antigen-presenting cells to induce naive lymph node T
      cells to proliferate and to express IFN-gamma, IL-4, IL-5, and IL-10 cytokine
      mRNAs. In contrast, neither adoptively transferred B7-2neg-B cells nor
      nonspecific B7-2pos-B cells were able to activate naive T cells. In addition,
      anti-B7-2 treatment prevented the in vivo expression of the IL-4, IL-5, and IFN
      gamma cytokine mRNA responses. Our results suggest a major role of autoantigen
      specific B7-2pos-B cells in breaking T cell tolerance to self-antigen.

PMID- 9186644
TI  - Immunoglobulin J chain. An early differentiation marker of human B cells.

PMID- 9186645
TI  - Inducible Fas-resistance mediated by IL-4 in activated B cells.

PMID- 9186646
TI  - Markedly diminished radiation-induced lymphocyte apoptosis in lpr mice suggests a
      role for Fas in eliminating damaged cells.

PMID- 9186647
TI  - Ig-specific T cells regulate the fate of the B cells during the immune response
      in a TCR transgenic mouse model.

PMID- 9186648
TI  - Expression of the tyrosine kinase Lyn during B cell receptor engagement and
      apoptosis.

PMID- 9186649
TI  - Lupus humoral autoimmunity after short peptide immunization.

PMID- 9186650
TI  - The regulation of murine lupus.

PMID- 9186652
TI  - Nucleosome-driven autoimmune response in lupus. Pathogenic T helper cell epitopes
      and costimulatory signals.

PMID- 9186651
TI  - Initiation of autoimmunity to self-proteins complexed with viral antigens.

PMID- 9186653
TI  - Phenotypic and functional characterization of human tonsillar subepithelial (SE)
      B cells.

PMID- 9186654
TI  - Natural autoantibodies, tolerance, and autoimmunity.

PMID- 9186655
TI  - Human peripheral B cell development. sIgM-IgD+CD38+ hypermutated germinal center
      centroblasts preferentially express Ig lambda light chain and have undergone mu
      to-delta switch.

PMID- 9186656
TI  - Mutually dependent T and B cell responses in germinal centers.

PMID- 9186657
TI  - A germinal center-like reaction in the nonlymphoid tissue of the synovial
      membrane.

PMID- 9186659
TI  - Microbial antigens can elicit autoantibody production. A potential pathway to
      autoimmune disease.

PMID- 9186658
TI  - Unique site of autoantibody production in Fas-deficient mice.
AB  - The inability of B and T lymphocytes from mice expressing the lpr mutation to
      express functional Fas on their cell surface leads to an immunoregulatory defect
      associated with excessive autoantibody production. Nevertheless, T-dependent
      antibody response to foreign antigens in these mice appears relatively normal. To
      better understand exactly how Fas/FasL interactions control autoantibody
      production, studies were undertaken to determine (1) what kind(s) of B cells are
      sensitive to Fas-mediated apoptosis and (2) where the autoantibody-producing
      cells in lpr mice are located. We found that B cells activated by CD40L are
      extremely sensitive as targets in assays of Th1 CMC. However, B cells that
      receive a complete signal through their sIgM antigen receptor acquire a FasL
      resistant phenotype. In situ analysis of splenic sections from lpr mice
      demonstrated that autoantibody-producing cells were uniquely localized to the T
      cell-rich inner PALS. A similar distribution pattern of IgG AFC was found in mice
      with chronic GVH disease. These data are consistent with the premise that the
      inner PALS, and not the germinal center, is the major site of FasL regulation of
      B cell activity and that, as a result of genetic or inducible loss of sensitivity
      to Fas-mediated apoptosis, autoreactive B cells may survive and differentiate in
      this location to cause serological autoimmunity.

PMID- 9186660
TI  - Positive and negative selection of human B lymphocytes in vitro.

PMID- 9186661
TI  - Anti-red blood cell immunoglobulin transgenic mice. An experimental model of
      autoimmune hemolytic anemia.

PMID- 9186662
TI  - Functional properties and molecular characteristics of autoantibodies associated
      with tight skin syndrome.

PMID- 9186663
TI  - Nuclear localization of autoantibodies. Novel insights into protein translocation
      and cellular function.

PMID- 9186664
TI  - Complement deficiency and autoimmunity.

PMID- 9186665
TI  - Clinical relevance of Fc gamma receptor polymorphisms.
AB  - Human IgG receptors are very heterogeneous and we currently distinguish three Fc
      gamma receptor classes specifying at least 12 receptor isoforms. On top of this
      complexity, Fc gamma R are further found to differ between different individuals.
      Polymorphisms have been identified for all three Fc gamma R classes. The best
      studied ones represent allelic variation of Fc gamma RIIa (CD32) and Fc gamma
      RIIIb (CD16). The Fc gamma RIIa polymorphism is now considered to be a heritable
      risk factor for autoimmune and infectious diseases, and support for a relevant
      role of the IIIb polymorphism has also been obtained. A detailed analysis of the
      exact contribution of each of these Fc gamma R polymorphisms in relation to
      previously implicated risk factors should unravel the pathophysiological
      importance of Fc gamma R polymorphisms in the near future.

PMID- 9186666
TI  - Rheumatoid factor autoantibodies in health and disease.
AB  - Recent advances in molecular biological and human cell hybridization technology
      have significantly advanced the knowledge of mechanisms that underlie human
      rheumatoid factor (RF) production. These advances have provided insight into the
      etiopathogenesis of synovial inflammation and lymphocyte recruitment in
      rheumatoid arthritis (RA) joints. We have examined the mechanisms that lead to RF
      production in RA patients and those that regulate RF production in normals. The
      studies revealed structural features that distinguish RF produced in normals from
      those produced in RA synovial tissue. There are significant differences in the
      use of VL and VH genes between the two RF populations. Furthermore, IgV genes
      encoding synovial RF in RA have extensive evidence for nucleotide changes,
      leading to amino acid replacement in the complementarity determining regions
      (CDRs). In addition, RF produced in RA synovia show evidence for affinity
      maturation, isotype switch to IgG RF, and repertoire shift indicative of a
      continued recruitment of B cells. Together with computer modeling and
      crystallographic studies, our data suggest that the mechanisms that operate on RF
      selection in RA synovia are similar to immune responses to exogenous antigens. In
      contrast, RF established from human immunized donors (HID) are characterized by a
      very low ratio of replacement to silent (R:S) nucleotide changes in the CDR1+2.
      In addition, there is little increase in affinity with increasing numbers of
      mutations. There is thus evidence for regulatory mechanisms that limit affinity
      maturation of RF in normals.

PMID- 9186667
TI  - Evidence for a selected humoral immune response encoded by VH4 family genes in
      the synovial membrane of a patient with RA.

PMID- 9186668
TI  - Identification and cloning of genes expressed by human tonsillar B lymphocyte
      subsets.

PMID- 9186669
TI  - Somatic mutation and CDR3 length of immunoglobulin lambda variable region genes
      in the synovium of patients with rheumatoid arthritis.

PMID- 9186670
TI  - Immunoglobulin variable region (IgV) gene expression in rheumatoid factors from
      monozygotic twins with rheumatoid arthritis.

PMID- 9186671
TI  - Comparison of structural characteristics of antisubnucleosome and anti-DNA
      monoclonal antibodies derived from lupus mice.

PMID- 9186672
TI  - Site-directed mutagenesis of recombinant human beta 2-glycoprotein I. Effect of
      phospholipid binding and anticardiolipin antibody activity.

PMID- 9186673
TI  - Herpes viruses in multicase families with rheumatoid arthritis and systemic lupus
      erythematosus.

PMID- 9186674
TI  - Use of phage expression to analyze regions of a human V4-34(VH4-21)-encoded IgG
      autoantibody required for recognition of DNA. No involvement of the 9G4 idiotope.

PMID- 9186675
TI  - Induction of autoimmunity. A role for the idiotypic network.

PMID- 9186676
TI  - B cell presentation of cartilage type II collagen to T cells.

PMID- 9186677
TI  - Correlation between HLA-DR sequence polymorphisms and rheumatoid factor
      production.

PMID- 9186678
TI  - Superantigens, VH gene polymorphism, and rheumatoid factor (RF) production.

PMID- 9186679
TI  - Regulation of rheumatoid factor production by B cells from healthy individuals
      and patients with rheumatoid arthritis.

PMID- 9186680
TI  - Tumor necrosis factor (TNF) enhances the locomotion of low-density human
      tonsillar B lymphocytes through the selective triggering of type II receptor.

PMID- 9186681
TI  - Treatments with tamoxifen and an antiestradiol antibody have beneficial effects
      on experimental SLE via cytokine modulation.

PMID- 9186682
TI  - Screening of immunological properties of vermiculine in selected model
      situations.

PMID- 9186683
TI  - Analysis of CD40-CD40 ligand interactions in the regulation of human B cell
      function.
AB  - CD40-CD40 ligand interactions play an essential role in T cell/B cell
      collaboration. The data presented in this review have served to widen the scope
      of CD40-CD40 ligand interactions to include initial activation, proliferation,
      differentiation, and isotype switching of B cells, as well as subsequent
      downregulation of B cell function. Moreover, CD40 ligand expression by activated
      B cells is likely to play an essential role in facilitating ongoing responses of
      stimulated B cells maturing in germinal centers. Finally, CD40 expression by
      activated T cells may also play an important role in regulating the function of
      helper T cells within germinal centers. In summary, emerging data have expanded
      the role of CD40-CD40 ligand interaction during T cell/B cell collaboration and
      have emphasized its potential to regulate many of the functions of both partners
      in this essential interaction involved in antibody production.

PMID- 9186684
TI  - CD40 and its ligand in autoimmunity.

PMID- 9186685
TI  - Regulation of T and B cell responses by modulating interactions between
      CD28/CTLA4 and their ligands, CD80 and CD86.
AB  - In recent years, it has become clear that the fate of lymphocyte interactions
      with antigen is determined not only by signals through antigen-specific
      receptors, but by interactions between pairs of accessory molecules. One such
      crucial pair of ligands is that between CD80/CD86, expressed by professional APCs
      and activated T and B cells, and CD28 (resting and activated T cells primarily)
      and CTLA4 (activated T cells). Signals in this system can amplify (CD28) or
      inhibit (CTLA4) T cell responses. The uses of soluble competitors for CD28 (CTLA4
      Ig) and agonists for the inhibitory receptor CTLA4 (CD80-Ig) offer therapeutic
      possibilities to tailor autoimmune responses in nonpathogenic directions.

PMID- 9186686
TI  - B cells present antigen to CD4+ T cells, but fail to produce IL-12. Selective APC
      for Th2 cell development?

PMID- 9186688
TI  - CDR3 fingerprinting of immunoglobulin kappa light chains expressed in rheumatoid
      arthritis. Evidence of antigenic selection or dysregulation of gene rearrangement
      in B cells.

PMID- 9186687
TI  - Oral administration of myelin induces antigen-specific TGF-beta 1-secreting T
      cells in multiple sclerosis patients.

PMID- 9186689
TI  - The accessory cell function of B-CLL B cells.

PMID- 9186690
TI  - Strand breaks in immunoglobulin gene hypermutation.

PMID- 9186692
TI  - Isolation and characterization of single anti-U1A-specific B cells from
      autoimmune patients.

PMID- 9186691
TI  - c-myc proto-oncogene expression by germinal center B cells isolated from human
      tonsils.

PMID- 9186693
TI  - The leukemic cells of chronic lymphocytic leukemia patients with autoimmune
      hemolytic anemia produce isotype-switched immunoglobulins that are preferentially
      encoded by the 51p1 and DP-50 VH genes.

PMID- 9186695
TI  - A sulfatide-reactive monoclonal antibody derived from a patient with multiple
      sclerosis binds to myelin in situ.

PMID- 9186694
TI  - CDRH3 length is the target of selection of disease-associated IgM autoantibodies.
AB  - The experiments outlined here provide evidence for positive selection of B-1
      lymphocytes secreting IgM autoantibodies in the autoimmune mev mice as a result
      of the reduced threshold of responsiveness to autoantigens because of PTP1C
      deficiency, which is targeted at the CDR3 length of the variable region of the
      heavy chain. In addition, characteristic differences in the size, hydrophobicity
      pattern, and relative local charge of the CDR3 of the heavy chain of disease
      associated IgM autoantibodies from moth-eaten mice help distinguish them from
      physiological natural autoantibodies present in normal mice.

PMID- 9186696
TI  - Fine specificity analysis of autoantibodies to T cell receptor CDR1 segments in
      rheumatoid arthritis.

PMID- 9186697
TI  - An anti-idiotypic (T14) antibody found commonly in patients with systemic lupus
      erythematosus that may be pathogenic.

PMID- 9186698
TI  - B cell response and histology of a retroviral infection in vivo.

PMID- 9186699
TI  - IgG-fibronectin complexes mimic antibodies to denatured collagen type II.

PMID- 9186701
TI  - Evidence for B cell oligoclonality in the blood and joints of patients with
      rheumatoid arthritis.

PMID- 9186700
TI  - Requirements for mIgM-triggered activation versus apoptosis in human B cells.

PMID- 9186703
TI  - Expression of an Ig VH gene, 51p1, is proportional to its germline gene copy
      number.

PMID- 9186702
TI  - Lactoferrin-reactive natural antibodies.

PMID- 9186704
TI  - Neutrophils and anti-Ro/SSA.

PMID- 9186705
TI  - Recurrent identical rearrangement and repeated expression of identical heavy and
      light chains in single anti-phosphatidylcholine B cells.

PMID- 9186706
TI  - Prevention of autoantibody production in lpr/lpr mice by transgenic expression of
      Fas on B cells.

PMID- 9186708
TI  - Anti-p53 autoantibodies in colon cancer patients.

PMID- 9186707
TI  - Bacterial immunomodulators affect programmed cell death of mouse spleen
      lymphocytes.

PMID- 9186709
TI  - Modulation of the autoimmune response in lupus mice by oral administration of
      attenuated Salmonella typhimurium expressing the IL-2 and TGF-beta genes.

PMID- 9186710
TI  - Autoimmune reactions induced by gliadin feeding in germ-free AVN rats and athymic
      nude mice. Animal models for celiac disease.

PMID- 9186711
TI  - Do certain autoantibodies produced in the course of human autoimmune blistering
      skin diseases behave as adhesion molecules?

PMID- 9186712
TI  - Characterization by molecular cloning an antigen reactive with antireticulin
      antibodies.

PMID- 9186713
TI  - CRI-EM is a human idiotype highly specific for scleroderma.

PMID- 9186714
TI  - Length diversity of immunoglobulin heavy-chain variable regions from rheumatoid
      arthritis synovium.

PMID- 9186715
TI  - Fibroblast growth factor-like autoantibodies in plasma from patients with
      multiple endocrine neoplasia type 1 and prolactinoma.

PMID- 9186716
TI  - The characterization and classification of neurotransmitter receptors.

PMID- 9186717
TI  - Protein structures in receptor classification.

PMID- 9186719
TI  - To what extent can binding studies allow the quantification of affinity and
      efficacy?

PMID- 9186718
TI  - Transduction is a major factor influencing receptor characterization.
AB  - Two state (agonist-antagonist) receptor systems may explain many discrepancies in
      receptor classification, but the role of transduction (G protein coupling) may be
      critical. We propose that in some instances synthetic agonists and antagonists
      may interact with the receptor in such a way as to modify coupling compared with
      endogenous agonists, and that the transduction system together with the local
      environment, may contribute more to the rank order of potency of agonists and
      antagonists than the receptor subtype as defined by structure. Allosteric
      interactions at ion channels and receptors require a modification of concepts of
      coupling. Imidazoline ligands have different efficacy in coupling alpha 2
      adrenoceptors to G proteins, compared with adrenaline and noradrenaline, and do
      not show a marked sodium shift, implying that the sodium site, and by implication
      the arginine switch, is implicated in the differential coupling. The alpha 2
      adrenoceptor labeled with a natural agonist does not show subtype selectivity
      whereas antagonist-labeled alpha 2-adrenoceptors show subtype selectivity. In the
      5-HT1A receptor, palmitoylation (of receptor or G proteins) allows the expression
      of different agonist states. Thus transduction and G protein coupling must be
      taken into account in receptor classification, even if the primary classification
      may be structural.

PMID- 9186720
TI  - Criteria for the classification of hormone receptors with implications for
      nomenclature. An impossible task?

PMID- 9186721
TI  - Do recombinant receptor assays provide affinity and potency estimates?

PMID- 9186722
TI  - How receptor mutagenesis may confirm or confuse receptor classification.

PMID- 9186723
TI  - A genome-based receptor nomenclature.

PMID- 9186724
TI  - Do recent operational studies indicate that a single state model is no longer
      applicable to G protein-coupled receptors?
AB  - Recent evidence suggests that unliganded G protein-coupled receptors exist in at
      least two states, an inactive conformation and an active conformation possessing
      affinity for the G protein even in the absence of agonist. The data accumulated
      so far for wild-type receptors imply that this is true for receptors for several
      hormones and receptor subtypes, and theoretically for all G protein-coupled
      receptors. The data now consist of studies implicating not only spontaneous
      receptor-G protein coupling, but also effector mechanisms and, in the case of
      transgenic mice over-expressing the human beta 2-adrenoceptor, physiologic
      responses at the level of the isolated tissue and in vivo. Furthermore, there
      appear to be ligands (inverse agonists) that can decrease the level of the
      constitutively active conformation of the receptor, and neutral antagonists can
      not only block classical agonist responses, but also inhibit the response of
      inverse agonists.

PMID- 9186725
TI  - Is promiscuity of G protein interaction an issue in the classification of
      receptors?
AB  - It is clear that the details of binding of different classes of agonist ligands
      to the same receptor may be distinct. This could result in subtle differences in
      the profile of G protein activation by individual ligands at the same receptor
      due to agonist-induced selection of conformational states of the receptor which
      favor interaction and ternary-complex formation with different G proteins. This
      can result in differences in the details of receptor pharmacology when measured
      at the level of effector output. Such differences are also likely to be dependent
      upon both the levels of expression of the receptor and the relevant G proteins
      and the G protein and effector enzyme isoform expression profile of a particular
      tissue. It would be foolish, however, to use such differences, in isolation, as a
      means to expand the classification of G protein-coupled receptors particularly
      when more molecular approaches to receptor classification are readily available.

PMID- 9186726
TI  - The classification of bioamine receptors. How helpful are molecular phylogenies?

PMID- 9186727
TI  - Neurokinin receptors. Comparison of data from classical pharmacology, binding,
      and molecular biology.

PMID- 9186728
TI  - The alpha and omega of G protein-coupled receptors. A novel method for
      classification.

PMID- 9186729
TI  - Evolutionary conservation of the 5-HT2B receptors.

PMID- 9186730
TI  - [3H]5-HT binding to 5-HT1nonA-nonB receptors in rat hypothalamus is not
      representative of 5-HT7 receptors.

PMID- 9186731
TI  - Working hypothesis on the classification of Cys-leukotriene receptors in airways.

PMID- 9186732
TI  - Cloning and functional expression of guinea pig atrial alpha 2-adrenergic
      receptor subtypes.

PMID- 9186733
TI  - Apparent heterogeneity of 5-HT2A receptors observed in functional studies with
      antagonists may reflect species-related differences.

PMID- 9186734
TI  - [3H]-RS-79948-197, a high affinity radioligand selective for alpha 2-adrenoceptor
      subtypes.

PMID- 9186735
TI  - Acylation differentiates two forms of agonist binding to rat 5-HT1A receptors.
      Palmitoylated G protein--agonist states?

PMID- 9186736
TI  - An improved method for analysis of competitive agonist/antagonist interactions by
      non-linear regression.

PMID- 9186737
TI  - ERK activation and cellular proliferation in response to muscarinic acetylcholine
      receptor agonists.

PMID- 9186738
TI  - Estimation of the relative potency of two glycine antagonists on NMDA-induced
      depolarizations in BRSC and ARCS.

PMID- 9186739
TI  - Functional study of the excitatory alpha-adrenoceptor in guinea pig ileum, in
      relation to the hypothesis of an atypical receptor.

PMID- 9186740
TI  - Functional change of the balance between alpha 1A and alpha 1B adrenoceptor
      populations after transplantation of the vas deferens to the intestine.

PMID- 9186741
TI  - Functional classification of non-competitive antagonism in vas deferens.

PMID- 9186742
TI  - M3 receptor mobilizes intracellular calcium in rat stomach fundus.

PMID- 9186743
TI  - Agonist binding properties for recombinant kappa opioid receptors expressed in
      CHO-K1 cells.

PMID- 9186744
TI  - The calcitonin gene-related peptide (CGRP) receptor in rat smooth muscles.

PMID- 9186745
TI  - GR127935 antagonizes the 5-HT1-like receptor-mediated external carotid
      vasoconstriction in vagosympathectomized dogs.

PMID- 9186746
TI  - Atypical beta-adrenoceptors in the rat vasculature.

PMID- 9186747
TI  - Interaction between H3-receptors and other prejunctional receptor systems in the
      isolated guinea pig duodenum.

PMID- 9186748
TI  - Cloned and native guinea pig 5-ht7 receptors. Characterization using an
      integrated approach.
AB  - Structural criteria, i.e., primary sequence homology, indicates a unique 5-HT
      subtype. Operational criteria suggest that this is also true, although no
      selective agonist or antagonist is available to fully define the receptor, and
      thus its function in vivo. Transductional data provide perhaps the weakest
      criterion to define the receptor, since at least two other subtypes (5-HT4 and 5
      ht6) signal via the same second messenger. These criteria, taken together,
      suggest that the cloned sequence represents an endogenously expressed 5-HT
      receptor and should be referred to as "5-HT7" receptors, rather than "5-ht7".

PMID- 9186749
TI  - Identification of a single residue responsible for agonist selectivity in the
      oxytocin-vasopressin receptors.

PMID- 9186750
TI  - 5-HT1D and 5-HT2B receptors mediate contraction of smooth muscle in human small
      intestine.
AB  - In conclusion, 5-HT has been shown to contract both circular and longitudinal
      muscle layers of human terminal ileum. By the use of selective antagonists, the
      receptors mediating these actions have been identified. In the circular muscle of
      human small intestine, 5-HT-induced contraction is mediated via a receptor of the
      5-HT1D sub-type, whereas a receptor of the 5-HT2B sub-type mediates the
      contractile response to 5-HT of longitudinal muscle layers.

PMID- 9186751
TI  - Heterogeneity of 5-HT receptors mediating secretion in the human intestine.
AB  - In conclusion, application of 5-HT has been shown to induce fluid secretion in
      both the small and large intestine of man. By the use of selective antagonists,
      the receptors mediating these effects have been identified and characterized. 5
      HT induces secretion across human ileal mucosa via a receptor of the 5-HT4 sub
      type, whereas a receptor of the 5-HT2A sub-type appears to mediate the effect in
      human sigmoid colon. The response in human ascending colonic mucosa cannot be
      definitively classified at this time, but may reflect the presence of a
      heterogenous receptor population.

PMID- 9186752
TI  - 13-Tert-butylergoline derivatives. Assessment of functional serotonergic 5-HT1A
      component.

PMID- 9186753
TI  - High level expression of the human 5-HT1D alpha serotonin receptor using the
      Semliki Forest Virus expression system.

PMID- 9186754
TI  - Different levels of receptor expression as a new procedure to estimate agonist
      affinity constant. Application to the metabotropic receptors.

PMID- 9186755
TI  - Sodium dependency of constitutive activity at 5-HT1D alpha/1D beta receptors.

PMID- 9186756
TI  - Macronutrient substitutes. Description and uses.

PMID- 9186757
TI  - Regulatory aspects of the introduction of new macronutrient substitutes.

PMID- 9186758
TI  - Energy balance: role of genetics and activity.
AB  - It is clear from the above discussion that much remains to be learned about both
      energy intake and energy expenditure. Obesity in humans is not likely to be
      caused by one gene, as it is in certain rodent models of obesity, such as the
      ob/ob mouse and the fa/fa rat. It is likely to be a polygenic condition in which
      numerous genes interact with each other and the environment to express the
      obesity phenotype. It is likely that genes that affect energy intake as well as
      genes that affect energy expenditure are involved. The role of leptin as a
      putative factor in signaling the extent of the fat mass to the central nervous
      system and controlling both food intake and energy expenditure is unclear at this
      time. The genetics of energy expenditure are also not clear at this time. There
      are mechanisms of nutrient partitioning, such as respiratory quotient and
      lipoprotein lipase activity, that are being discovered to be important. In
      addition, insulin sensitivity is likely to play a role in the etiology of
      obesity. Much more investigation will be required before we have a clearer
      picture of how the above-named factors interact, what the genetic contribution to
      this is, and how important each factor is to the overall phenotypic expression of
      obesity.

PMID- 9186759
TI  - Effect of fat intake on energy balance.
AB  - Most epidemiological studies indicate that obesity is more prevalent in
      populations consuming high fat diets. Furthermore, changes from a traditional to
      a westernized life style, characterized by a high-fat diet and decreased physical
      activity, result in dramatic increases in the prevalence and incidence of obesity
      in Native Americans, Pacific Islanders, and African populations. A possible
      explanation for the epidemic of obesity in response to high-fat intake can be
      found in the "oxidative hierarchy" that regulates macronutrient balance in the
      human body. Although carbohydrate and protein balances seem promptly regulated,
      fat balance is not. Short and midterm studies show that, unlike carbohydrate and
      protein intake, fat intake does not promote fat oxidation. Thus, "excess" fat
      intake results in fat deposition. As fat mass increases, so does fat oxidation,
      and a new equilibrium is reached when fat oxidation matches fat intake. However,
      there are large interindividual differences in this compensatory response to
      increased fat intake. Substrate oxidation is a familial trait, and individuals
      with a low fat-to-carbohydrate oxidation ratio are more prone to develop obesity
      than those with a high fat-to-carbohydrate oxidation ratio. Genetics may
      influence nutrient partitioning by influencing the activity of key enzymes of
      intermediate metabolism, such as lipoprotein lipase, beta-hydroxyl acyl CoA
      dehydrogenase, and acetyl CoA carboxylase.

PMID- 9186760
TI  - Carbohydrates and energy balance.
AB  - In the early 1970s carbohydrates (CHOs) were believed to induce overconsumption
      and excess fat deposition. They are now perceived to protect against these
      consequences. This paper evaluates the evidence for this change of interpretation
      by considering (1) the energy content of CHOs, (2) the energetic efficiency with
      which they are handled by the body, and (3) their effects on appetite, relative
      to other macronutrients. CHOs are the least energy-dense macronutrients (delta
      Hc) and exhibit the greatest variability in digestibility. Doubling the usual
      levels of nonstarch polysaccharides (fiber) may decrease digestibility of a
      Western diet by 5%. De novo lipogenesis from dietary CHO is energetically
      inefficient but very limited on Western diets, which are relatively high in fat.
      There appears to be a hierarchy (protein > CHO > fat) in the extent to which the
      stores of the macronutrients are autoregulated by oxidation. Excess CHO intake
      tends to promote storage (but not de novo synthesis) of fat. The thermogenic
      effects of CHO are therefore relatively limited on Western diets. Per MJ of
      energy ingested, macronutrients differentially affect satiety (protein > CHO >
      fat) under conditions where fat is disproportionately energy dense.
      Isoenergetically dense loads of fat and CHO exert less pronounced differences on
      satiety. Under some conditions HC diets promote excess energy intakes. There is
      little evidence that a CHO-rich diet, or one with intense sweeteners, promotes
      spontaneous weight loss.

PMID- 9186761
TI  - Impact of macronutrient substitutes on the composition of the diet and the U.S.
      food supply.

PMID- 9186762
TI  - Impact of macronutrient-substituted foods on food choice and dietary intake.

PMID- 9186763
TI  - Impact of the use of reduced-fat foods on nutrient adequacy.

PMID- 9186764
TI  - Macronutrient substitutes and weight-reduction practices of obese, dieting, and
      eating-disordered women.

PMID- 9186765
TI  - Dietary fiber: nutritional lessons for macronutrient substitutes.
AB  - The wide array of low-fat foods containing soluble fibers have the potential for
      helping in weight loss or weight control. Consumption of soluble fibers in
      sufficient quantities has been shown to lower serum lipid concentrations and to
      improve glycemic response. Some individuals could, eventually, consume a
      significant portion of their soluble dietary fiber from processed foods
      containing soluble-fiber fat substitutes. Changes in dietary fiber and starch
      sources increase the amount of fermentable material reaching the colon. Short
      chain fatty acids thus produced are used as an energy source by colonocytes and
      may inhibit hepatic cholesterol synthesis. However, colonic fermentation can also
      result in flatulence or diarrhea. In addition, some diets high in soluble fiber
      have been shown to change intestinal cell morphology in rats. The possible
      benefits from consumption of a diet high in soluble fiber fat substitutes in
      serum lipid reduction, glycemic response improvement, and/or weight reduction as
      well as potential problems in flatulence, mineral absorption, and colonic cell
      hyperproliferation should be investigated.

PMID- 9186766
TI  - Appropriate animal models for clinical studies.
AB  - Results from experiments with animal models can provide useful information
      relevant to human diet studies. They may indicate approximate levels of
      supplementation required to see an effect on the end-point measure of interest.
      They also allow investigation of metabolic responses that require invasive tissue
      sampling inappropriate for human studies. Animal studies carry the advantages of
      cost-effectiveness, speed, and control of potential confounding variables.
      However, results from animal studies cannot be directly extrapolated to clinical
      trials due to the absence of potential nutrient interactions, environmental
      stimuli, and learned food preferences and aversions that are experienced by human
      subjects.

PMID- 9186767
TI  - Nutritional aspects of macronutrient-substitute intake.

PMID- 9186768
TI  - Fat and sugar substitutes and the control of food intake.

PMID- 9186769
TI  - Food intake regulation in children. Fat and sugar substitutes and intake.
AB  - A series of experiments exploring children's responsiveness to manipulations of
      energy density and macronutrient content of foods have been reviewed to assess
      the nutritional impact of macronutrient substitutes on children's intake. In
      these experiments, the focus is on the extent to which the energy content of
      foods was a salient factor influencing children's food intake, and macronutrient
      substitutes were used as tools to investigate this issue. Therefore, although
      several different macronutrient substitutes have been used in this research, we
      do not have a parametric set of experiments systematically assessing the impact
      of a variety of macronutrient substitutes. Given this, what can we conclude from
      the existing data? When the energy density and macronutrient content of foods is
      altered through the use of macronutrient substitutes that reduce the energy
      content of foods, children tend to adjust for the missing energy, although this
      adjustment may be partial and incomplete. This suggests the possibility that when
      macronutrient substitutes are used to reduce the energy content of foods,
      children's energy intake may be reduced. This adjustment, however, will most
      likely be less than a "calorie for calorie" reduction. In addition, even among
      young children, there are individual differences in the extent to which children
      adjust their intake in response to macronutrient and energy manipulations. The
      data are more extensive and particularly clear for cases in which CHO
      manipulations are used to alter energy density, but there is evidence for
      adjustments in energy intake in response to alterations of the fat content of the
      diet. The compensation for energy is not macronutrient specific; that is, when
      the fat content of food is reduced to reduce energy density of foods, children do
      not selectively consume fat in subsequent meals. This means that manipulations of
      macronutrient content of foods that reduce foods' energy content may not result
      in alterations of energy intake, but because these adjustments in energy intake
      are not macronutrient specific, changes in the overall macronutrient composition
      of children's diets can be obtained. There does not appear to be anything unique
      or special about the effects of macronutrient substitutes on children's intake;
      their effects are similar to those produced by other manipulations of
      macronutrient and energy content accomplished without macronutrient substitutes
      (e.g., augmenting foods with fat or carbohydrate to produce macronutrient
      differences). The research also indicates that under conditions that minimize
      adult attempts to control how much and what children eat, children can adjust
      their food and energy intake in response to the alterations of macronutrient and
      energy content of foods. Whether or not young children adjust food intake to
      compensate for energy-density changes depends upon their opportunity to control
      their own food intake as opposed to having their intake controlled by others.
      Young children's ability to adjust intake in response to alterations in the
      energy density of foods can be readily disrupted by the imposition of controlling
      child-feeding practices that attempt to regulate what and how much children eat.
      We believe that early experiences, including child-feeding practices imposed by
      parents, are major factors contributing to the etiology of individual differences
      and gender differences in the behavioral controls of food intake that can occur
      in response to the energy content of foods. The extent to which children respond
      to energy density of the diet has major implications for the effects of fat and
      sugar substitutes on children's intake. If children who are responsive to energy
      density consume substantial amounts of foods containing macronutrient
      substitutes, they should show some adjustments in intake to compensate for
      reduced energy, so that the impact of macronutrient substitutes on energy intake
      may be relatively small. However, changes in macronutrient com

PMID- 9186770
TI  - Beyond calories: other benefits of macronutrient substitutes. Effects on chronic
      disease.

PMID- 9186772
TI  - Oil-soluble vitamin content of new reduced-fat and fat-free margarines. Potential
      implications for vitamin E intake.

PMID- 9186771
TI  - Replacement of dietary fat with fat-free margarine alters vitamin E storage in
      rats.

PMID- 9186773
TI  - The evolution of carbohydrate intake in the Slovak Republic during the economic
      transformation.

PMID- 9186774
TI  - Weight gain of rats consuming full-fat versus reduced-fat foods.

PMID- 9186775
TI  - Subunits I and II of Dictyostelium cytochrome c oxidase are specified by a single
      open reading frame transcribed into a large polycistronic RNA.
AB  - A single open reading frame (ORF) encoding cytochrome c oxidase subunit I and II
      (cox1/2) was identified in the mitochondrial genome of the slime mold
      Dictyostelium discoideum. The cox1 coding region shares intron positions with its
      counterparts in fungi and algae. Northern blot analysis, using exon and intron
      specific probes, suggests that the cox1/2 gene is transcribed as part of a large,
      efficiently processed, polycistronic RNA.

PMID- 9186776
TI  - Functional regions of the H(+)-ATPase inhibitory protein from ox heart
      mitochondria.
AB  - Derivatives of the inhibitor protein (IF1) of the mitochondrial H(+)-ATP
      synthase, bearing deletions at the N- or C-terminal ends, were tested for their
      abilities (a) to bind to the synthase, (b) to inhibit its ATPase activity and (c)
      to respond to energisation of the mitochondrial membrane. Deletion of nine
      residues from its N-terminus, or ten from its C-terminus had little effect on any
      of these three properties of IF1. Further deletions from the N-terminus (up to
      residue 17) led to an increase in binding affinity but a reduced ability to
      inhibit ATPase activity and to form a stable ATPase-IF1 complex. Removal of five
      more residues from the N-terminus (up to residue 22) reduced these abilities
      further, but also decreased binding affinity by an order of magnitude. It was
      concluded that residues 10-17 of IF1 interact with F1 in a way which modulates
      the stability and function of the interaction between F1 and IF1.

PMID- 9186777
TI  - Identification of domains on the 43 kDa chlorophyll-carrying protein (CP43) that
      are shielded from tryptic attack by binding of the extrinsic 33 kDa protein with
      photosystem II complex.
AB  - The structural association of the spinach 33 kDa extrinsic protein with the 43
      kDa chlorophyll-carrying protein (CP43) in oxygen-evolving photosystem II (PS II)
      complexes was investigated by comparing the peptide mappings and N-terminal
      sequences of the trypsin-digested products of NaCl-washed PS II membranes, which
      bind the 33 kDa protein, with those of CaCl2-washed PS II membranes, which lack
      the 33 kDa protein. (1) Peptide from N-terminus to Arg26 of CP43, which is
      exposed to stromal side, was digested in both PS II membranes, independent of
      binding of the 33 kDa protein. (2) Peptide bond of Arg357-Phe358 located in the
      large extrinsic loop E of CP43, which is exposed to lumenal side, was cleaved by
      trypsin in CaCl2-washed PS II membranes but not in NaCl-washed PS II membranes.
      This indicates that the region around Arg357-Phe358 in loop E of CP43 is shielded
      from tryptic attack by binding of the 33 kDa protein to PS II. (3) Trypsin
      treatment of CaCl2-washed PS II membranes also cleaved peptide bond between
      Lys457 and Gly458 in C-terminal region of CP43, while no cleavage of this region
      was detected by trypsin treatment of NaCl-washed PS II membranes. This implies
      that a conformational change of the C-terminal region of CP43 which is exposed to
      stromal side occurred upon removal of the 33 kDa protein, which makes the C
      terminal region accessible to trypsin. (4) Release of peptide from Gln60 to C
      terminus of the alpha-subunit of cytochrome b-559 was detected only in trypsin
      treatment of CaCl2-washed PS II membranes, indicating that the C-terminal region
      of this subunit is shielded from tryptic attack by binding of the 33 kDa protein.
      (5) The PS II membranes, in which Arg357-Phe358, Lys457-Gly458 of CP43 and the C
      terminal part of the cytochrome b-559 alpha-subunit had been cleaved by trypsin,
      was no longer able to bind the 33 kDa protein. This strongly suggests that a
      domain in loop E of CP43 and/or the C-terminal region of the cytochrome b-559
      alpha-subunit are necessary for binding of the extrinsic 33 kDa protein to PS II.

PMID- 9186778
TI  - Uptake of creatine phosphate into heart mitochondria: a leak in the creatine
      shuttle.
AB  - CrP uptake into isolated rat heart mitochondria was studied using silicone oil
      centrifugation. Further, the involvement of the mitochondrial adenine nucleotide
      translocase was examined by measuring CrP accumulation in mitochondria in the
      presence of substrates and inhibitors of the ATP/ADP-carrier and by investigating
      uptake kinetics in liposomes reconstituted with purified bovine heart adenine
      nucleotide translocase protein. CrP is accumulated in the matrix space of
      isolated rat heart mitochondria and mitoplasts. The uptake is inhibited by
      carboxyatractyloside, a specific inhibitor of the mitochondrial adenine
      nucleotide translocase, and by ADP, phosphoenolpyruvate, 3-phosphoglycerate and
      pyrophosphate, compounds which are able to bind to the carrier. It is not
      inhibited when the mitochondrial membrane potential is decreased. CrP is
      transported into reconstituted liposomes at a rate which is about 3 orders of
      magnitude lower than the rate for ATP uptake. The transport is sensitive to
      temperature change and to carboxyatractyloside. It is concluded that CrP is
      specifically taken up by heart mitochondria via the mitochondrial adenine
      nucleotide translocase. The transport in mitochondria in situ is facilitated by
      the close local and functional interaction of the mitochondrial creatine kinase
      and the adenine nucleotide translocase within contact sites between inner and
      outer mitochondrial membrane. A certain amount of CrP synthesized by the
      mitochondrial creatine kinase thus escapes its usage at cytosolic energy
      consuming processes.

PMID- 9186779
TI  - Mobilization of iron from neoplastic cells by some iron chelators is an energy
      dependent process.
AB  - Iron (Fe) chelators of the pyridoxal isonicotinoyl hydrazone (PIH) class may be
      useful agents to treat Fe overload disease and also cancer. These ligands possess
      high activity at mobilizing 59Fe from neoplastic cells, and the present study has
      been designed to examine whether their marked activity may be related to an
      energy-dependent transport process across the cell membrane. Initial experiments
      examined the release of 59Fe from SK-N-MC neuroblastoma (NB) cells prelabelled
      for 3 h at 37 degrees C with 59Fe-transferrin (1.25 microM) and then reincubated
      in the presence and absence of the chelators for 3 h at 4 degrees C or 37 degrees
      C. Prelabelled cells released 4-5% of total cellular 59Fe when reincubated in
      minimum essential medium at 4 degrees C or 37 degrees C. When the chelators
      desferrioxamine (DFO; 0.1 mM) or PIH (0.1 mM) were reincubated with labelled
      cells at 4 degrees C, they mobilized only 4-5% of cellular 59Fe, whereas as 37
      degrees C, these ligands mobilized 21% and 48% of cell 59Fe, respectively. The
      lipophilic PIH analogue, 311 (2-hydroxy-1-naphthylaldehyde isonicotinoyl
      hydrazone; 0.1 mM), which exhibits high anti-proliferative activity, released 10%
      and 53% of cellular 59Fe when reincubated with prelabelled cells at 4 degrees C
      and 37 degrees C, respectively. Almost identical results were obtained using the
      SK-Mel-28 melanoma cell line. These data suggest that perhaps temperature
      dependent mechanisms are essential for 59Fe mobilization from these cells.
      Interestingly, the metabolic inhibitors, 2,4-dinitrophenol, oligomycin, rotenone,
      and sodium azide, markedly decreased 59Fe mobilization mediated by PIH, but had
      either no effect or much less effect on 59Fe release by 311. Considering that an
      ATP-dependent process was involved in 59Fe release by PIH, further studies
      examined 4 widely used inhibitors of the multi-drug efflux pump P-glycoprotein (P
      gp). All of these inhibitors, namely, verapamil (Ver), cyclosporin A (CsA),
      reserpine (Res) and quinine (Qui), decreased 59Fe mobilization by PIH but had
      little or no effect on 59Fe release mediated by analogue 311. Further, both CsA
      and Ver increased the proportion of ethanol-soluble 59Fe within cells in the
      presence of PIH, suggesting inhibited transport of the 59Fe complex from the
      cell. However, when PIH-mediated 59Fe release was compared between a well
      characterized Chinese hamster ovary cell line (CHRB30) expressing high levels of
      P-gp and the relevant control cell line (AuxB1), no appreciable difference in the
      kinetics of 59Fe release were found. In contrast, it was intriguing that the
      CHRB30 cells released more 59Fe into control medium (i.e., without PIH) than the
      AuxB1 control line (16.7% compared to 5.9%, respectively). In summary, the
      results suggest that a temperature- and energy-dependent process was involved in
      the efflux of the PIH-59Fe complex from the cells. In contrast, 59Fe release
      mediated by 311 was temperature-dependent but not energy-dependent, and could
      occur by simple diffusion or passive transport. Further studies investigating the
      membrane transport of Fe chelators may be useful in designing regimes that
      potentiate their anti-neoplastic effects.

PMID- 9186780
TI  - The reduction of acetylpyridine adenine dinucleotide by NADH: is it a significant
      reaction of proton-translocating transhydrogenase, or an artefact?
AB  - Transhydrogenase is a proton pump. It has separate binding sites for NAD+/NADH
      (on domain I of the protein) and for NADP+/NADPH (on domain III). Purified,
      detergent-dispersed transhydrogenase from Escherichia coli catalyses the
      reduction of the NAD+ analogue, acetylpyridine adenine dinucleotide (AcPdAD+), by
      NADH at a slow rate in the absence of added NADP+ or NADPH. Although it is slow,
      this reaction is surprising, since transhydrogenase is generally thought to
      catalyse hydride transfer between NAD(H)--or its analogues and NADP(H)--or its
      analogues, by a ternary complex mechanism. It is shown that hydride transfer
      occurs between the 4A position on the nicotinamide ring of NADH and the 4A
      position of AcPdAD+. On the basis of the known stereospecificity of the enzyme,
      this eliminates the possibilities of transhydrogenation(a) from NADH in domain I
      to AcPdAD+ wrongly located in domain III; and (b) from NADH wrongly located in
      domain III to AcPdAD+ in domain I. In the presence of low concentrations of added
      NADP+ or NADPH, detergent-dispersed E. coli transhydrogenase catalyses the very
      rapid reduction of AcPdAD+ by NADH. This reaction is cyclic; it takes place via
      the alternate oxidation of NADPH by AcPdAD+ and the reduction of NADP+ by NADH,
      while the NADPH and NADP+ remain tightly bound to the enzyme. In the present
      work, it is shown that the rate of the cyclic reaction and the rate of reduction
      of AcPdAD+ by NADH in the absence of added NADP+/NADPH, have similar dependences
      on pH and on MgSO4 concentration and that they have a similar kinetic character.
      It is therefore suggested that the reduction of AcPdAD+ by NADH is actually a
      cyclic reaction operating, either with tightly bound NADP+/NADPH on a small
      fraction (< 5%) of the enzyme, or with NAD+/NADH (or AcPdAD+/AcPdADH) unnaturally
      occluded within the domain III site. Transhydrogenase associated with membrane
      vesicles (chromatophores) of Rhodospirillum rubrum also catalyses the reduction
      of AcPdAD+ by NADH in the absence of added NADP+/NADPH. When the chromatophores
      were stripped of transhydrogenase domain I, that reaction was lost in parallel
      with 'normal reverse' transhydrogenation (e.g., the reduction of AcPdAD+ by
      NADPH). The two reactions were fully recovered upon reconstitution with
      recombinant domain I protein. However, after repeated washing of the domain I
      depleted chromatophores, reverse transhydrogenation activity (when assayed in the
      presence of domain I) was retained, whereas the reduction of AcPdAD+ by NADH
      declined in activity. Addition of low concentrations of NADP+ or NADPH always
      supported the same high rate of the NADH-->AcPdAD+ reaction independently of how
      often the membranes were washed. It is concluded that, as with the purified E.
      coli enzyme, the reduction of AcPdAD+ by NADH in chromatophores is a cyclic
      reaction involving nucleotides that are tightly bound in the domain III site of
      transhydrogenase. However, in the case of R. rubrum membranes it can be shown
      with some certainty that the bound nucleotides are NADP+ or NADPH. The data are
      thus adequately explained without recourse to suggestions of multiple nucleotide
      binding sites on transhydrogenase.

PMID- 9186781
TI  - B-cell superantigens: molecular and cellular implications.
AB  - B cell superantigens are proteins that are capable of immunoglobulin variable
      region mediated binding interactions with the naive B cell repertoire at
      frequencies that are orders of magnitude greater than occur for conventional
      antigens. Within this review we discuss recent observations regarding the
      molecular basis of these interactions and the distribution of superantigen
      binding capacities in different human B cell populations. These findings and
      current predictions regarding the relevance of these proteins to the physiologic
      development of immune repertoires are also discussed.

PMID- 9186782
TI  - Staphylococcal protein A binding to VH3 encoded immunoglobulins.
AB  - Staphylococcal protein A (SPA) is a B-cell superantigen which binds specifically
      to the variable region of human VH3 encoded antibodies. We undertook to identify
      the VH3 regions involved in the interaction with SPA by producing mutant
      antibodies in the baculovirus expression system. We had previously shown that a
      single amino acid change at position 57 in the CDR2 of a human SPA nonbinding VH3
      encoded rheumatoid factor converted it to an SPA binder, implicating CDR2 in SPA
      binding. When regions of the mutated binder were exchanged with those from a
      mouse nonbinding antibody, the pattern of SPA binding indicated that residues in
      FR1, CDR2 and FR3 are involved in the interaction between VH3 encoded antibodies
      and SPA. In addition, all three regions are simultaneously required for SPA
      binding to occur. When any one of the three regions was altered, SPA binding was
      severely disrupted.

PMID- 9186783
TI  - B cell superantigens: potential modifiers of the normal human B cell repertoire.
AB  - Staphylococcal protein A (SPA), HIV gp120, and staphylococcal enterotoxins (SE)
      are B cell superantigens that induce VH specific B cell responses. In addition,
      the red blood cell antigens, i/I, have some features of a B cell superantigen.
      Binding of SPA, SE and HIV gp120 are VH family specific, whereas binding of i/I
      is VH gene specific. SPA and HIV gp120 function by stimulating VH3-expressing B
      cells, whereas SE appear to function by enhancing survival of the appropriate VH
      expressing B cells. Moreover, HIV gp120 has been shown to delete VH3-expressing B
      cells. In this review, we describe evidence that shows how these superantigens
      may play a role in shaping the normal B cell repertoire.

PMID- 9186784
TI  - HIV-1 gp120: a novel viral B cell superantigen.
AB  - The envelope glycoprotein of the human immunodeficiency virus (HIV-1), gp120, has
      recently been characterized as a novel immunoglobulin superantigen (Ig-SAg)
      [1,2]. Analogous to the interaction of SAgs with T cells, gp120 binds to an
      unusually large proportion of immunoglobulins (lgs) from HIV-uninfected
      individuals; most, if not all of these Igs are members of the VH3 family [3].
      Functionally, gp120 preferentially stimulates VH3 B cells in vitro. This
      stimulation correlates with an in vivo VH3 activation during HIV infection.
      Curiously, this initial activation is followed by a subsequent depletion of VH3
      expressing B cells as individuals progress to AIDS. In this article we will
      review our current understanding of the superantigenic properties of HIV gp120.
      Specifically we will focus on structural aspects of the binding interaction. on
      the ontological development of these superantigen-binding antibodies, and on
      potential roles that this unconventional Ig-pathogen interaction might play in
      the pathogenesis of HIV-induced disease.

PMID- 9186785
TI  - B cell superantigens in HIV-1 infection.
AB  - HIV-I infection affects many of the cellular components vital for the maintenance
      of immune homeostasis. Similar to the T cell superantigen effect on T cell
      expansion and depletion in AIDS. HIV components with B cell superantigenic
      properties could be responsible for the observed B cell activation and skewing of
      VH family usage. Current data on possible B cell superantigen properties of HIV
      proteins (gp120) are mostly based on studies describing the clonality and VH
      family usage of immunoglobulins in HIV infection. Various laboratories reported
      independently an unusual skewing of the VH-repertoire of antibodies that appears
      not to be random. According to these observations, an enrichment of VH1 and VH4
      family-paralleled a depletion of VH3 family-utilizing anti-HIV-1 gp120 and p24
      antibodies in HIV-1 infected individuals and a loss of total VH3+ Ig in patients
      with late stages of AIDS. Polyclonal and monoclonal (VH1, VH4, and VH5) anti-p24
      and gp120 antibodies share a crossreactive idiotype (IF7). IF7 like antibodies
      were found in the serum of HIV-1 infected individuals, persisting in the course
      of infection, perhaps contributing to the depletion of VH3 Ig. Furthermore a
      restriction of clonal heterogeneity of anti-p24 and anti-gp120 antibodies was
      detected by isoelectric focusing and indicated by skewed kappa/lambda light chain
      isotype ratios, indicating clonal dominance of certain sets of anti-HIV-1
      antibodies during infection. Taken these findings together, a strong case for the
      involvement of a B cell superantigen can be made, although the mechanism of B
      cell depletion is not fully understood.

PMID- 9186786
TI  - Ig VH-dependent interaction between immunoglobulins and CD4.
AB  - CD4 interacts with the immunoglobulin (Ig)-VH domains by a virtue of its solvent
      exposed C and C strands. These two strands also contribute to the full HIV-gp120
      binding and participate significantly in binding to class II MHC molecules. In
      this paper we hypothesize that any high-affinity interaction between serum (or
      membrane-expressed) Ig and CD4 may have impact on early T cell activation events.
      The existing data provide evidence for different outcomes of a high affinity
      Ig/CD4 interaction on T cell proliferation and cytokine secretion: costimulation
      and inhibition. We will also discuss how a low affinity CD4/Ig interaction could
      play an important role in B cell stimulation initiated through surface Ig
      receptors, and how CD4 may be involved in shaping the B cell repertoire.

PMID- 9186787
TI  - Clinical subtypes of bipolar mixed states: validating a broader European
      definition in 143 cases.
AB  - OBJECTIVE: To validate and clinically characterize mixed bipolar states derived
      from the concepts of Kraepelin and the Vienna School and defined as sustained
      instability of affective manifestations of opposite polarity--that usually
      fluctuate independently of one another--in the setting of marked emotional
      perplexity. METHOD: Our criteria for mixed states represent a modified "user
      friendly" operationalization of these classical concepts. We compared 143 mixed
      state patients, so defined, with 118 DSM III-R manic patients, systematically
      evaluated with the Semistructured Interview for Depression (SID) in our in
      patient and day-hospital facilities. RESULTS: The two groups were comparable from
      demographic and familial standpoints (including family history for bipolar
      disorder). Mixed states were predominant in the past history of index mixed
      patients who were more likely to have experienced stressors and to have attempted
      suicide; manic and hypomanic episodes were more common in the past history of the
      index manic patients who, in addition, had more episodes and hospitalizations.
      Although rates of chronicity and rapid cycling were not significantly different
      in the two groups, the modal episodes in the mixed states were 3-6 months, and in
      mania they were less than 3 months. Two thirds of both groups arose from a
      dysregulated baseline temperamental dysregulation, which in manics, was largely
      hyperthymic, and in mixed patients, was both hyperthymic and depressive. Of our
      143 mixed states, only 54% met the DSM III-R criteria for mixed states (which
      conformed to "dysphoric mixed mania"); of the remaining, 17.5% could be described
      as "mixed agitated psychotic depressive states" with irritable mood and flight of
      ideas, and 26% as "unproductive-inhibited manic" with fatigue and indecisiveness.
      The family history and course of these "non-DSM III-R" mixed states were
      essentially similar to DSM III-R mixed states. LIMITATION: Family history could
      not be obtained blind to clinical status in patients with severe psychotic mood
      states. CLINICAL RELEVANCE: These data favor the classical European approach to
      mixed states over the grossly under-inclusive current official diagnostic
      systems. CONCLUSION: The phenomenology of mixed states is more than the mere
      superposition of opposite affective symptoms and, in many instances, it
      represents an expansive-excited phase intruding into a depressive temperament,
      and a melancholic episode intruding into a hyperthymic temperament.

PMID- 9186788
TI  - The efficacy of imipramine and psychotherapy in early-onset chronic depression: a
      reanalysis of the National Institute of Mental health Treatment of Depression
      Collaborative Research Program.
AB  - The authors compared the effectiveness of Cognitive Behavioral Therapy (CBT),
      Interpersonal Psychotherapy (IPT), Imipramine Clinical Management (ICM) to
      Placebo Clinical Management (PCM) for outpatients with early-onset chronic
      depression (N = 65) in the National Institute of Mental Health (NIMH) Treatment
      of Depression Collaborative Research Program (TDRP). The post-treatment
      depression scores of the CBT. IPT, and ICM groups were not significantly
      different from the PCM group. We did not find a relationship between the duration
      of Major Depression and response to a specific treatment. Studies are needed to
      determine if combining psychotherapy with medication improves social functioning
      and enhances the quality of life for patients with chronic depression.

PMID- 9186789
TI  - Evaluating the diagnostic specificity of the Munich Personality Test dimensions
      in major depression.
AB  - This study explored the diagnostic specificity of the Munich Personality Test
      (MPT) in major depression, comparing its scores between patients with major
      depression, patients with panic disorder and control subjects. One of the 6
      dimensions of the MPT, Rigidity, had been developed based on Tellenbach's
      description of depressive personality, and it was expected that especially this
      personality dimension would demonstrate a good facility for describing a specific
      personality feature of major depression. Comparisons were made in 2 ways:
      ignoring the effects of current depression and anxiety on the personality
      scorings; and partialling out these effects. Results of the 2 analyses differed
      radically. Scores on Rigidity and isolation Tendency were significantly different
      between groups, even after the effects of current depression and anxiety were
      partialled out. The multiple comparison procedure revealed that the depressive
      patients were differentiated from both the panic patients and the controls only
      in the dimension of Rigidity. The results of this study suggest that the Rigidity
      dimension of MPT may have a strong capability for describing the specific
      personality feature of depressive patients, and that the MPT may be quite useful
      for studies, particularly prospective ones, investigating premorbid personality
      of depression.

PMID- 9186790
TI  - A chromosome 18 genetic linkage study in three large Belgian pedigrees with
      bipolar disorder.
AB  - The contribution of genetic factors to the susceptibility for affective disorders
      has been firmly established. Recent reports found evidence for a susceptibility
      locus for affective disorders in 2 regions on chromosome 18. We describe 3 large
      Belgian pedigrees with multiple patients with affective disorders. Both
      chromosome 18 regions were investigated in the 3 families, using parametric and
      nonparametric segregation methods. In the pericentromeric region, all evidence
      was against a disease gene in our families. Also the data obtained for the distal
      part of 18q, argue against a genetic susceptibility factor in our sample.

PMID- 9186791
TI  - The influence of cognitive variables on recovery in depressed inpatients.
AB  - Forty two unipolar depressed inpatients were assessed on admission to hospital
      and again two years after the onset of the index episode. Fifty seven per cent of
      the sample (n = 24) fulfilled NIMH recovery criteria within this period. Older
      age, female gender, severity of index episode, median prior duration of episode,
      higher levels of dysfunctional attitudes and low self-esteem significantly
      predicted chronicity of depression. Backward stepwise logistic regression
      identified that three of these variables measured at the time of admission:
      severity of index depression, higher levels of dysfunctional attitudes related to
      the need for approval, and low self-esteem provided a robust logistic model for
      predicting outcome. However, the small sample size and statistical analysis
      employed means that replication of our research is required. Larger scale studies
      could also include a factor analysis so that the common elements within the
      different instruments may be detected. If the association between cognitive
      dysfunction and chronicity is confirmed, we would recommend that inpatient
      treatment strategies are revised to incorporate more overt psychosocial
      interventions.

PMID- 9186792
TI  - Relationship between perception of facial emotions and anxiety in clinical
      depression: does anxiety-related perception predict persistence of depression?
AB  - Within the framework of interpersonal theories on depression, it was postulated
      1) that an anxiety-related mood-congruent bias with respect to the perception of
      facial expressions could be demonstrated in clinically depressed patients: 2)
      that the perception of negative facial emotions would be associated with co
      occurring anxiety levels rather than with depression, and 3) that the putative
      anxiety-related bias would predict the subsequent course of depression. Such
      relationships would support the possible causal role of negative biases for the
      persistence of depression. Thirty-nine depressed patients (thirty-six patients
      met the criteria for major depression, two had a dysthymic disorder and one
      patient suffered from a cyclothymic disorder) were studied. The patients judged
      schematic faces with respect to the emotions they express (fear, happiness,
      anger, sadness, disgust, surprise, rejection and invitation) at admission (T0),
      and after 6 (T1) and 30 (T2) weeks. Severity of depression (BDI) and anxiety (SCL
      90) were assessed at these three points. We found considerable support for the
      first 2 hypotheses: a) The perception of negative emotions was related to anxiety
      but not to depression (at T0 this association was significant and at T1 and T2
      tendencies were found); b) When the level of depression was controlled for,
      significant relationships remained (emerged) between anxiety and the perception
      of negative emotions at each of the three different time points; c) Anxiety and
      perception of negative emotions covaried within subjects when large changes in
      depression/anxiety were involved, i.e. after 30 weeks. This relationship
      disappeared when depression change was partialled out. The third hypothesis was
      not confirmed: The perception of negative emotions did not predict the course of
      depression. Although a direct relationship with depression persistence and a
      negative bias in the perception of interaction-relevant stimuli (i.e. facial
      emotions) in anxious depressed patients could not be found, the existence of such
      anxiety-related negative bias forms indirect evidence for the notion that this
      negative bias may mediate rejective attitudes of others towards depressives and
      consequently may contribute to an unfavorable course of depression.

PMID- 9186793
TI  - Investigation of pharmacokinetics and of possible adverse effects in infants
      exposed to tricyclic antidepressants in breast-milk.
AB  - We have studied ten breast-feeding mothers who were prescribed tricyclic
      antidepressant drugs and have also compared their infants' development with a
      similar group (n = 15) who were bottle-fed. Concentrations of tricyclic drugs in
      maternal plasma and urine, in fore-milk and hind-milk and in infant plasma (n =
      6) and urine (n = 9) were measured by gas chromatography (GC) and by an enzyme
      immunoassay (EIA). The fat concentration in milk was also measured. Infants
      health and development were monitored by physical examination and by the Bayley
      Scales of Infant Development up to 30 months. The amounts of tricyclic drugs and
      their principal metabolites in maternal plasma were significantly correlated with
      the oral dose and with the amounts in breast-milk. Drug concentrations in fore
      milk, but not in hind-milk, increased in line with its fat content, which was
      maximal in hind-milk. Correlations between gas chromatographic and enzyme
      immunoassays of maternal samples were high provided that the values for
      amitriptyline and nortriptyline were excluded; immunoreactivities to these
      compounds were abnormally high, suggesting that metabolites were also being
      measured by EIA. The daily doses of drugs ingested by breast-fed infants were
      about 1% of the maternal dose/kg and the immunoassay detected very small amounts
      of tricyclics in infants' plasma and urine. No acute toxic effects were found in
      the ten medicated breast-fed infants and there was no evidence of developmental
      delays in comparison with bottle-fed infants. Although the number of subjects in
      this study is small, when taken in conjunction with other published findings, we
      have not found any reason to prevent mothers who are taking established tricyclic
      antidepressants from breast-feeding their babies if they want to do so.

PMID- 9186794
TI  - The prevalence of affective and anxiety disorders in primary care practice in
      Hungary.
AB  - The lifetime and point prevalence of affective and anxiety disorders were
      investigated with the aid of the DIS questionnaire in 15 primary care practices
      among patients aged 18 to 60. According to the DSM-III-R criteria, 43% of the
      eligible 301 patients had had some kind of affective or anxiety disorder till the
      time of the assessment. Major depression was found to be the most common lifetime
      diagnosis (18%). At the time of the investigation 15% of the patients were
      suffering from affective or anxiety disorder (point prevalence) calling for
      clinical therapy. Females had significantly higher numbers of lifetime and point
      diagnoses of affective and anxiety disorders. Sixty percent of patients failed to
      report psychiatric complaints to their doctor, and in social phobia this figure
      was as high as 87%. Our results are in accordance with international findings and
      underline the need to diagnose and treat psychiatric patients already at the
      stage of the primary care service.

PMID- 9186795
TI  - Course of depression in patients with comorbid anxiety disorders.
AB  - This study examined the extent to which the presence of comorbid anxiety disorder
      affected the course of depression. 650 depressed outpatients visiting general
      medical clinicians and mental health specialists were followed for 1 or 2 years.
      All types of anxiety increased the probability of a new depressive episode among
      patients with subthreshold depression. Co-occurring panic and phobia decreased
      the likelihood of remission. The initial number of depressive symptoms was
      greatest among depressed patients with comorbid anxiety and this relatively
      higher level persisted over two years. The findings emphasize the poor clinical
      prognosis associated with comorbid anxiety disorder.

PMID- 9186796
TI  - Post-partum blues and mild depressive symptomatology at days three and five after
      delivery, A French cross sectional study.
AB  - This cross-sectional work studies the prevalence of post-partum blues on days 3
      and 5 after delivery and the links between post-partum blues and depressive
      symptomatology, using standardised interviews and rating scales (Kennerley and
      Gath Blues Scale. MADRS) to screen a consecutive series of 104 women on days
      three and five after a normal delivery. This study stresses the possibility of a
      difference between the symptomatology of a benign "classical" post-partum blues,
      and that of a more intense blues closer to the spectrum of depressive mood
      disorders and perhaps post-natal depression.

PMID- 9186797
TI  - Seasonal variation in postdexamethasone cortisol values in depressed inpatients.
      Results of least squares cosine spectral analysis.
AB  - Recently, a significant seasonal variation in postdexamethasone (post-DST)
      cortisol values in depressed patients has been reported. This study aimed to
      investigate seasonal variation in post-DST cortisol values in 269 depressed
      patients admitted to a psychiatric ward during 70 consecutive months. By means of
      analysis of variance no significant differences could be detected in post-DST
      values in depressed men or women, alone or together, between the 12 months, the
      period November-February versus March-October, or between the tour quartiles. By
      means of spectral analysis no significant seasonal rhythms, i.e. annual or
      harmonic rhythms, could be found in the time series of post-DST cortisol values
      either in the total group of depressed patients or in depressed women separately
      (n = 190). Spectral analysis showed a significantly biannual rhythm in the post
      DST cortisol values in depressed men, with peaks in June and December and troughs
      in March and September. This biannual rhythm explained 12.4% of the variance in
      the post-DST cortisol values of depressed men. The results show that there is a
      significant seasonal variation in post-DST cortisol values in depressed men, but
      not in depressed women.

PMID- 9186798
TI  - Heart rate variability before and after treatment with electroconvulsive therapy.
AB  - It has been suggested that depression may be associated with decreased
      parasympathetic activity. Based on this work, we tested the hypothesis that
      treatment of depression with electroconvulsive therapy (ECT) would result in a
      relative increase in cardiac vagal (parasympathetic) activity. Changes in
      respiratory sinus arrhythmia, a marker of cardiac parasympathetic activity, were
      examined in nine patients with depressive episodes before and after ECT using
      spectral analysis. Hamilton Depression Rating Scale scores decreased
      significantly. In terms of the heart rate measures, RR interval tended to
      decrease and the amplitude of respiratory sinus arrhythmia decreased
      significantly following the course of ECT. This reduction in respiratory sinus
      arrhythmia contributed to the overall decrease in RR interval variability.
      Additionally, the magnitude of symptom improvement as measured by the Hamilton
      Scale correlated with the decrease in amplitude of the respiratory sinus
      arrhythmia. We report that treatment of depression with ECT was associated with a
      relative decrease in parasympathetic activity, in contrast to our initial
      hypothesis of a relative increase. This finding may not be related to the ECT per
      se but rather to the resolution of depression, as there was a significant
      correlation between the decrease in Hamilton Depression Rating Scale scores and
      decrease in parasympathetic activity. Further work is necessary to better
      understand the autonomic changes associated with depressive illness and the
      clinical risks and benefits associated with various treatment modalities.

PMID- 9186799
TI  - Depression, psychosocial variables and occurrence of life events among patients
      with cancer.
AB  - Depressive disorders and psychosocial related factors were investigated in 113
      patients one year after the diagnosis of cancer. Patients with an ICD-10
      diagnosis of depression (31% of the sample) showed higher external locus of
      control, poorer social support, higher incidence of undesirable and/or
      uncontrollable events than non-depressed patients. They also differed in
      reporting more frequently a life-time history of emotional disorders, inability
      to adjust to the diagnosis of cancer and in having a lower score on the
      performance status. Of these factors, past psychiatric history, early
      maladjustment to cancer, poor social support and low performance status were
      predictors of depressive symptoms. However, because of the cross-sectional nature
      of the study, no conclusion regarding a causal relationship between depression
      and psychosocial variables is possible.

PMID- 9186800
TI  - Affective instability and impulsivity in personality disorder. Results of an
      experimental study.
AB  - Affective instability in borderline personality disorder is due to a marked
      reactivity to environmental events. The present study focused on the relationship
      between affective instability and impulsivity in personality disorder. It used an
      experimental approach in the form of an affect-stimulation design based on the
      presentation of a short story which allowed for an analysis of affective
      responses in regard to quality, intensity, and alterations over time. Impulsive
      personalities showed a strong intensity of affective responses us well as a
      tendency towards rapid affect alterations supporting the theory of poor affect
      regulation in subjects with impulsive self-harming behaviour. Results suggest
      that affective instability is a crucial part of impulsive personality
      functioning.

PMID- 9186801
TI  - Atypical depressive symptoms in seasonal and non-seasonal mood disorders.
AB  - The authors examined the rates of atypical depression and prevalence of specific
      atypical symptoms in patients with seasonal versus non-seasonal depression. Fifty
      three patients with seasonal affective disorder (SAD) were compared to 54
      patients with non-seasonal major depressive disorder (MDD) using the atypical
      depression diagnostic scale (ADDS). SAD patients scored significantly higher than
      non-seasonal MDD patients in hyperphagia and hypersomnia, and significantly lower
      in interpersonal sensitivity and other rejection avoidance. There was no
      difference in the rate of ADDS diagnosis of atypical depression. Differences
      between atypical depression and SAD suggest that they are separate subtypes of
      depression with an overlapping symptom picture.

PMID- 9186802
TI  - Clinical characteristics and biological parameters in temperamental clusters of
      suicide attempters.
AB  - A sample of 215 suicide attempters was categorized in a cluster analysis into
      four groups according to temperamental trails. Monoamine metabolites in the
      cerebrospinal fluid were analysed (n = 106). Dexamethasone suppression tests
      (DST) were performed (n = 154) and the activity of the enzyme monoamine oxidase
      in platelets (pl-MAO) was assessed (n = 103). Patients belonging to the two
      clusters with the most deviant temperament profiles (nos 2 and 3) were young and
      scored high on the Beck Hopelessness Scale and the Suicide Assessment Scale.
      "Cluster 3" ("neurotic, impulsive, aggressive") patients often had dysthymia and
      axis II, cluster B diagnoses (e.g. borderline or histrionic personality).
      "Cluster 2" ("neurotic and introverted") patients often had major depression. The
      "Cluster 1", with on the whole a normal temperament profile, had significantly
      higher levels of post-DST cortisol than the other clusters. The "Cluster 4" had a
      normal temperament profile. Adjustment disorders were most common in "Cluster 1"
      and "Cluster 4". The monoamine metabolite levels did not differ between the
      clusters, and the differences in pl-MAO activity disappeared after adjusting for
      age and gender. The results suggest that temperament profiles in suicide
      attempters are related to psychiatric diagnoses, suicidality, hopelessness, and
      post-DST cortisol, but are not predictive of completed suicide.

PMID- 9186803
TI  - Psychosocial factors and the long-term course of major depression.
AB  - Fifty-nine subjects participated in a telephone follow-up interview 6 years after
      being hospitalized with a severe major depressive episode and 5 years after
      completing a 12 month follow-up study. Patient information was used to provide a
      rating of symptom-free (n = 19), episodic (n = 30), or chronic (n = 10) that
      described each patient's long-term course of illness. Few variables from the
      acute stage were related to long-term course of illness; however, early patterns
      of global and family functioning, number of life events, and rapid reduction in
      depressive symptomatology were found to be of prognostic significance. For
      patients whose depression is severe enough to warrant hospitalization, the
      pattern of functioning in the first few months after discharge from hospital is a
      strong indicator of the future long-term course.

PMID- 9186804
TI  - Brain hypometabolism of glucose in low-weight depressed patients and in anorectic
      patients: a consequence of starvation?
AB  - As low-weight anorectic patients presented a global as well as a regional
      absolute hypometabolism of glucose, we investigated a population of ten age- and
      sex-matched low-weight depressed patients without anorexia nervosa to evaluate
      the impact of weight loss on cerebral glucose metabolism evaluated by positron
      emission tomography and [18F]-fluorodeoxyglucose. Ten age- and sex-matched
      healthy volunteers were used as controls. Absolute global and regional glucose
      activity was significantly lower in anorectic and low weight depressed patients
      than in control subjects. Anorectic patients compared with normal control
      subjects also showed lower relative metabolism of glucose in the parietal cortex.
      Within patients, absolute hypometabolism of glucose seems to be a consequence of
      low-weight while there is a positive correlation between absolute metabolism of
      glucose and body mass index.

PMID- 9186805
TI  - Platelet [3H]imipramine and [3H]paroxetine binding in depressed patients.
AB  - [3H]Paroxetine and [3H]imipramine binding to blood platelet membranes was
      simultaneously measured in 63 control subjects and 18 patients with DSM-III-R
      criteria for major depression with melancholia. Both binding sites showed
      significantly different (p < 0.001) maximum binding (Bmax) and equilibrium
      dissociation constant (Kd) values. Age was not correlated with either
      [3H]imipramine Bmax or Kd values, but a negative correlation was found between
      [3H]paroxetine Bmax and age in healthy controls. Furthermore, depressed patients
      showed significantly lower [3H]imipramine Bmax values (p < 0.001) and higher Kd
      values (p < 0.001) in comparison to the control group. No differences were
      observed in [3H]paroxetine Bmax and Kd values between the two groups.

PMID- 9186806
TI  - Kinetics of immunological parameters in patients with malignant melanoma treated
      with hyperthermic isolated limb perfusion.
AB  - Kinetics of immunological parameters such as natural killer (NK) cell activity
      and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin
      stimulation were investigated using peripheral leukocyte fractions of melanoma
      patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum
      concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were
      quantified during and after HILP. It was found that NK cell activity was
      augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week
      after HILP with statistical significance. NK cell activities in the cells
      isolated from perfused and non-perfused circulations were equally augmented
      during HILP in two patients examined. Serum concentrations of sICAM-1 in the
      patients who received HILP also increased 24 h or even 1 week after HILP. The
      stimulation of these immune competent cells and upregulation of sICAM-1 by HILP
      were independent of the stages of melanoma patients at the time of HILP or the
      doses of agents which were used for the infusion during HILP. The origin of cells
      which shed sICAM-1 into the serum of the patients who received HILP remains to be
      further investigated.

PMID- 9186807
TI  - Characteristics of T cell lines established from skin lesions of Behcet's
      disease.
AB  - Hypersensitivity to a streptococcal antigen is postulated to be the pathogenesis
      of Behcet's disease. We analyzed T lymphocyte-phenotypes infiltrated in cutaneous
      pustular lesions in Behcet's disease and found that CD4+ T cells were predominant
      components although CD8+ T cells were also present in the lesion. In addition, we
      established T cell lines from pustular lesions of the four patients with a
      streptococcal antigen, KTH-1. Two of the cell lines showed the cell surface
      markers of CD8+TCR alpha beta +, and expressed mRNAs for interleukin (IL)-8,
      tumor necrosis factor (TNF) alpha, and perforin. Two other T cell lines expressed
      the cell surface markers for CD4+TCR alpha beta +. Cytokine expression pattern of
      the two CD4+ T cell lines revealed that one is Th1 type and the other is Th2
      type. The Th2 type cell line showed marked proliferation with autologous
      peripheral blood mononuclear cells, suggesting that the self-reactive T cells
      play some role on the pathogenesis of Behcet's disease.

PMID- 9186808
TI  - Monocyte chemotactic and activating factor (MCAF/MCP-1) has an autoinductive
      effect in monocytes, a process regulated by IL-10.
AB  - MCAF (MCP-1) a member of the chemokine-beta-family known to be chemotactic for
      monocytes is believed to play a significant role in several inflammatory
      processes, both immuno-pathological disorders, such as atherosclerosis,
      psoriasis, chronic inflammatory diseases of the liver and lungs, and during the
      normal immune response against microorganisms. This chemokine is produced
      spontaneously by monocytes, and in the present article we also demonstrate that
      MCAF induces its own production in monocytes. The methods used are two
      dimensional SDS-PAGE gel electrophoresis. Western-blotting and ELISA
      quantification of supernatant from monocyte cultures stimulated with MCAF (1, 10,
      100 ng ml). Also, we found that this process is regulated by IL-10 (100 ng ml).
      Our results suggest that monocytes migrating to a site of inflammation due to the
      local production of the chemokine MCAF/MCP-1 further enhance the focal
      accumulation of monocytes by producing and releasing bioactive MCAF MCP-1.

PMID- 9186809
TI  - Inhibition of ultraviolet B-induced skin erythema by N-nitro-L-arginine and N
      monomethyl-L-arginine.
AB  - Ultraviolet B (UVB)-irradiated human keratinocytes and human endothelial cells
      release nitrogen oxides, i.e. nitric oxide (NO). S-nitrosothiols, hydroxylamine
      (H2NOH) as well as ammonia (NH3) formed from L-arginine. Generation of these
      compounds was time and concentration-dependent and decreased by both N-monomethyl
      L-arginine (L-NMMA) and N-nitro-L-arginine (L-NA). UVB radiation of the cells
      resulted in a concomitant increase of soluble guanylate cyclase (sGC) activity
      which was inhibited by L-NMMA and L-NA. S-nitrosothiols formed during the
      irradiation of the cells directly increased purified sGC activity by a mechanism
      characteristic of release of NO from a carried molecule. UVB-irradiated cells
      promptly increased thiobarbituric acid reacting substance (TBARS) (estimated as
      malondialdehyde. MDA) production which were inhibited by desferrioxamine. In in
      vivo experiments using guinea pigs subjected to UVB radiation, a Protection
      Factor (PF) of 2.25 +/- 0.75 was calculated when an emulsified cream formulation
      containing L-NMMA (1% w/w) and L-NA (1% w/w) was applied to their skin. In human
      volunteers subjected to UVB radiation, a dose-dependent increase of PF was
      observed. When an emulsified cream formulation containing L-NMMA (1% w/w) and L
      NA (1% w/w) was applied to their skin the PF was 2.15 +/- 0.80: by increasing the
      concentration of L-NMMA (1% w/w) and L-NA (2% w/w) the PF was 4.25 +/- 1.25. The
      present results indicate that UVB radiation acts as a potent stimulator of human
      keratinocytes and endothelial cells to release nitrogen oxides that may diffuse
      out of the keratinocytes and endothelial cells, activating sGC in neighboring
      smooth muscle cells. This may be a major part of the integrated response of the
      skin leading to vasodilation and erythema.

PMID- 9186810
TI  - The promoter of an androgen dependent gene in the hamster flank organ.
AB  - Hamster flank organs are useful for studying androgen-dependent growth of hair
      follicles and sebaceous glands. A cDNA clone (FAR-17a) was isolated from the
      hamster flank organ, whose expression was highly sensitive to androgen. The mRNA
      level of this gene was reduced after castration but reappeared after testosterone
      treatment. To elucidate the mechanism of expression of this gene regulated by
      androgen we isolated a genomic clone, from a hamster genomic library, that
      includes the promoter and upsteam region. The promoter region was used to drive a
      luciferase reporter gene in Cos 7 cells. This construct was activated five to six
      times higher over a control plasmid lacking the promoter region. We tested the
      effects of testosterone by transfection of the reporter plasmid into androgen
      dependent SC-3 cells. The results showed up to fivefold stimulation after the
      addition of androgen. The sequence of this promoter region was analyzed and the
      transcription factor binding sites were predicted. Since no obvious androgen
      responsive elements were included in the promoter region, we suggest that the
      stimulation of the reporter construct has to be mediated indirectly by androgen
      dependent transcription factor(s).

PMID- 9186811
TI  - Peripheral blood neutrophil rheology measured by micropore filtration reflects
      Behcet's disease activity well.
AB  - Activated neutrophils take a long time to pass through a narrow lumen like a
      micropore, and are supposed to play a deteriorating effect on microcirculation.
      Although the activation of neutrophils has been demonstrated in Behcet's disease,
      nobody analyzes the clinical activity of the disease by means of the rheological
      measure of neutrophils activity. Using a micropore (pore diameter 5 microns)
      filtration technique, we measured the filtration time of peripheral blood
      neutrophils, as a rheological measure of their activity, in order to determine
      the clinical activity of Behcet's disease. Twenty-one patients with Behcet's
      disease and 14 healthy control individuals were enrolled in the study. Symptoms
      and signs exhibited in the patients led us to distinguish the Behcet's disease
      into inactive and active cases. The latter were further differentiated into cases
      with absent symptoms and with present symptoms. Neutrophil filtration times were
      11.5 +/- 4.8 s in the active cases with present symptoms, which were
      significantly (P < 0.05) larger than those (7.4 +/- 1.9 s) in the active cases
      with absent symptoms. The latter filtration times were further significantly (P <
      0.001) larger than values (3.7 +/- 1.3 s) in the inactive cases and also those
      (4.8 +/- 1.2 s) in control subjects. Furthermore, increases in the filtration
      time obtained immediately after the exposure of cells to the chemotactic peptide
      formyl-methionyl-leucyl-phenylalanine (FMLP: 10 nM) were significantly (P < 0.01)
      larger in the active cases with present symptoms than those in the active cases
      with absent symptoms. The latter were also larger, but not significantly, than
      those in the inactive cases, and were significantly (P < 0.01) larger than those
      in control subjects. The present results demonstrate that the micropore
      filtration method reflects well the rheological activity of neutrophils as well
      as the clinical status of Behcet's disease. This method is much better than the
      measurement of O2 production to differentiate between active cases with absent
      symptoms and inactive patients or even control individuals. Furthermore, it is
      more sensitive and useful than laboratory data like the CRP value or the number
      of peripheral blood neutrophils.

PMID- 9186812
TI  - Eosinophil-colony stimulating activity in blister fluid of bullous pemphigoid.
AB  - We examined eosinophil-colony stimulating activity in blister fluid or serum
      obtained from patients with bullous pemphigoid using the methylcellulose semi
      solid hematopoietic stem cell culture system, and demonstrated that the blister
      fluid of patients with bullous pemphigoid generated strong eosinophil-colony
      stimulating activity. This evidence suggests that eosinophil-colony stimulating
      activity in blister fluid probably influences the induction of eosinophilia in
      bullous pemphigoid.

PMID- 9186813
TI  - Age-related discontinuous changes in the in vivo fluorescence of human facial
      skin.
AB  - We measured the 325-nm laser-induced fluorescence of the skin of the face and
      ventral forearm in seventy Japanese female volunteers, and evaluated the effects
      of age and exposure to sunlight. The subjects were arbitrarily grouped into 10
      year age-groups. In slightly exposed areas such as the ventral forearm, the
      average laser-induced intensity ratio at 390 nm to 430 nm showed no significant
      differences with the age group. In areas markedly exposed to sunlight such as the
      corners of the eyes and mouth, the average laser-induced intensity ratio showed a
      discontinuous decrease with age. These findings suggested that dermal fluorophore
      changes differ with the skin areas and are affected by sunlight exposure.

PMID- 9186814
TI  - Hair follicle dermal papilla cell lines from p53-knockout mice.
AB  - We have attempted to establish a cell line from hair follicle dermal papillae
      microdissected from vibrissa of mice lacking p53 tumor suppressor gene. The hair
      follicle dermal papillae were obtained from three types of mice: null knockout,
      hetero-knockout and wild type litters. Continuous cell lines with short doubling
      time were obtained only from null knockout litter-mates. Dermal papilla cells
      from either the hetero-knockout or wild type mice did not multiply well, and died
      within three passages; provided, however, that in only three cases out of 40
      primary dermal papilla implants from two hetero-knockout mice, the cell culture
      reached 29 passages with a much slower growth rate than the cell lines from the
      null-knockout mice. These data are in accordance with the notion that the loss of
      p53 function is closely related to perpetuation of cell cycles and or
      immortalization.

PMID- 9186816
TI  - Growth hormone (GH) response to GH-releasing hormone in short children: lack of
      correlation with endogenous nocturnal GH secretion.
AB  - The growth hormone (GH) response to iv administration of GH-releasing hormone
      (GHRH, 0.3 microgram/Kg) was evaluated in 21 short children (13 boys and 8 girls,
      age 6.7-13.8 yr). Fourteen had familial short stature and/or constitutional
      growth delay, one had coeliac disease, and 6 were ultimately diagnosed as non
      classical GH deficiency or neurosecretory dysfunction on the basis of subnormal
      integrated spontaneous GH concentrations (ICGH). The response was compared with
      12-h spontaneous GH secretion measured every 30 min from 20:00 to 08:00. Mean
      ICGH ranged from 2.0-17.7 micrograms/l, with a maximum nocturnal GH peak ranging
      from 5.4-74 micrograms/l. The maximum GH peak after GHRH ranged from 9.4-50
      micrograms/l, and the area under the curve (AUC) from 406-3012 micrograms.min/l.
      No correlation was found between the maximum GH peak and the AUC after GHRH and
      the maximum overnight GH peak, the ICGH and the overnight AUC. This study
      confirms that the GH response to GHRH is highly variable among short children
      with a wide range of spontaneous GH secretion, and that this response is not
      correlated with the spontaneous ability to secrete GH.

PMID- 9186815
TI  - Evaluation of bone turnover in postmenopause, vertebral fracture, and hip
      fracture using biochemical markers for bone formation and resorption.
AB  - The purpose of this study is to evaluate bone turnover in postmenopausal status
      and established osteoporosis with vertebral fracture and hip fracture by
      assessing bone biochemical markers. Subjects were 50 healthy premenopausal
      subjects, 44 healthy postmenopausal subjects, 30 osteoporotic patients with
      vertebral fracture, and 31 osteoporotic patients with hip fracture. Alkaline
      phosphatase, osteocalcin, PICP, ICTP, NTx, free deoxypyridinoline, total
      pyridinoline and deoxypyridinoline were measured. In postmenopause, both Z-scores
      of bone formation markers and resorption markers were around 1-2. In
      osteoporosis, although Z-scores of bone formation markers were 0.4-2.8,
      resorption markers were 2.3-9.5. Moreover, Z-scores of resorption markers were
      higher in hip fracture than in vertebral fracture. These results indicate that
      bone formation and resorption increased and balanced in postmenopausal status.
      However, bone resorption increased more than bone formation and did not balance
      at all in osteoporosis. This imbalance is greater in hip fractures than in
      vertebral fractures.

PMID- 9186817
TI  - Effects of histaminergic antagonists on the GH-releasing activity of GHRH or
      hexarelin, a synthetic hexapeptide, in man.
AB  - The role of histamine in the neural control of GH secretion in man is still
      unclear, although a stimulatory influence has been hypothesized in man. To
      clarify this point, in 7 normal young women (23-28 yr) in their early follicular
      phase, we studied the effect of the histaminergic blockade by diphenhydramine
      (DPH, 80 mg os at -60 min) on the GH response to GHRH (2 micrograms/Hg iv) or
      Hexarelin (HEX, 2 micrograms/kg iv), a synthetic hexapeptide with strong GH
      releasing effect. In 6 of the 7 women the effect of terfenadine (TRF, 120 mg os
      at -60 min), another H1-receptor antagonist, on the GH response to GHRH or HEX
      was also studied. As HEX has also PRL- and ACTH-releasing activity and histamine
      has been shown to have a stimulatory role in the neural control of these
      hormones, the effects of DPH or TRF on the HEX-induced PRL. ACTH and cortisol
      release were also studied. GHRH induced a GH rise (peak, mean +/- SEM: 35.4 +/-
      6.5 vs 2.5 +/- 1.1 micrograms/l, p < 0.02, n = 7; 34.7 +/- 7.9 vs 3.9 +/- 1.5
      micrograms/l, p < 0.02, n = 6) lower (p < 0.05) than that elicited by HEX (49.1
      +/- 8.5 vs 3.9 +/- 1.0 micrograms/l, p < 0.01, n = 7; 48.7 +/- 8.9 vs 3.2 +/- 0.8
      micrograms/l, p < 0.01, n = 6). DPH inhibited the GH response to both GHRH (AUC:
      453.9 +/- 104.7 vs 1223.7 +/- 202.6 micrograms*min/l, p < 0.05) and HEX (922.0 +/
      215.4 vs 1636.4 +/- 267.5 micrograms*min/l, p < 0.05), although the HEX-induced
      GH rise persisted higher than that induced by GHRH (p < 0.05). TRF did not modify
      the GHRH-induced GH rise (950.5 +/- 369.2 mg*min/l vs 1115.3 +/- 255.6
      micrograms*min/l) as well as the somatotrope responsiveness to HEX (1163.2 +/-
      188.7 vs 1427.3 +/- 323.3 mg*min/l). HEX also significantly increased PRL (13.9
      +/- 3.1 vs 6.5 +/- 0.8 micrograms/l, p < 0.03), ACTH (31.1 +/- 6.6 vs 16.6 +/-
      2.9 pg/ml, p < 0.02) and cortisol (96.6 +/- 6.3 vs 82.2 +/- 6.2 micrograms/L, p <
      0.05) levels. PRL, ACTH and cortisol responses to HEX were unaffected by DPH
      (536.5 +/- 85.6 vs 599.5 +/- 129.2 micrograms*min/l, 1068.5 +/- 306.0 vs 1282.8
      +/- 222.0 pg*min/ml and 4277.4 +/- 588.4 vs 4738.3 +/- 355.3 micrograms*min/l,
      respectively) as well as by TRF (621.3 +/- 110.4 vs 530.3 +/- 131.4
      micrograms*min/L, 972.4 +/- 189.6 vs 1060.2 +/- 224.7 pg*min/ml and 6203.8 +/-
      1329.5 vs 5141.2 +/- 295.5 micrograms*min/l, respectively). In conclusion, our
      findings are against the hypothesis of a major role of H1-receptor-mediated
      histaminergic influence on GH secretion in humans. In fact, the H1-histaminergic
      blockade by TRF does not affect the GH response to GHRH or HEX; the inhibitory
      effect of DPH may probably be due to its intrinsic anticholinergic activity. Our
      data also confirm that Hexarelin releases more GH than GHRH and demonstrate that
      its effect on GH, PRL and ACTH release is not mediated by H1-receptors.

PMID- 9186818
TI  - Twenty-four hour melatonin pattern in acromegaly: effect of acute octreotide
      administration.
AB  - We investigated the melatonin (MT) circadian rhythm before and after somatostatin
      (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with
      active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2
      hours over a 48-h span; after 24-h basal blood collection, octreotide
      (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7
      healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition
      over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample,
      IGF-1 levels were measured by immunoradiometric assay in basal and after
      octreotide morning samples. The comparisons were made by Mann-U-Withney and
      Wilcoxon test as appropriate; the existence of a MT circadian rhythm was
      validated by cosinor analysis; GH and MT values were correlated by Pearson's
      correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had
      significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of
      the MT rhythms in acromegalics were significantly lower than in the controls (p <
      0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value:
      22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH
      concentrations were significantly increased in acromegalics in comparison with
      the control group. Octreotide administration significantly reduced GH, restoring
      a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not
      different from controls. Mean amplitude still remained lower than controls (p <
      0.0006), with an earlier acrophase (median 00:01 h). No significant correlation
      was found between individual GH and MT levels. Our data indicate a reduction of
      MT circadian secretion in acromegaly, due especially to a blunted nocturnal
      increase with earlier MT peak; moreover, acute octreotide administration increase
      MT levels without modifying amplitude and phase of night-time secretion
      significantly. These findings suggest a negative interrelationship between GH and
      MT secretions or a facilitatory influence of somatostatin on daytime MT release
      only. This partial recovery of pineal secretion after octreotide in acromegalics
      could be a clinically significant contribution to improve their quality of life,
      considering that MT is involved in the regulation of several important functions.

PMID- 9186819
TI  - Thyroid volume and function in patients with acromegaly living in iodine
      deficient areas.
AB  - The aim of our study was to evaluate the size and function of the thyroid in
      patients with acromegaly. In 39 patients concentrations of HGH, PRL, TSH, T3 and
      T4 were measured and the thyroid volume was calculated with the using of
      ultrasound examination. The control group comprised 5 patients with acromegaly in
      a stage of remission and 98 controls. We concluded that the size of the goiter in
      patients with acromegaly depends on serum concentration of HGH, but it does not
      depend on the concentration of TSH, T3, T4 and PRL. Goiter is present in 87% of
      patients with acromegaly, 46% of them are nodular goiters. The thyroid function
      in acromegaly is normal.

PMID- 9186820
TI  - Developmental patterns of serum 3 alpha-androstanediol glucuronide.
AB  - 3 alpha-androstanediol glucuronide (3 alpha diolG) is a marker of peripheral
      tissue androgen metabolism. There are no previous data regarding complete
      paediatric reference ranges for 3 alpha diolG. In order to obtain reference
      values for 3 alpha diolG we have measured serum levels of 3 alpha diolG in 283
      healthy children and adolescents, 146 boys and 137 girls, age 1 month to 20 years
      and 28 adults. A non-extraction, solid phase radioimmunoassay employing a
      polyclonal antiserum that is specific for 3 alpha diolG was used to measure serum
      3 alpha diolG levels (intra assay variation 5.1-10.1%, inter assay variation 2.7
      9.0%). There was a strong sex and age dependence (r = 0.8; p < 0.0001) of 3 alpha
      diolG levels throughout childhood and adolescence with males showing
      significantly higher levels of the androgen than females (p < 0.05). 3 alpha
      diolG serum levels (nmol/l +/- SD) correlated significantly with pubertal stage
      (p < 0.01). Interestingly, in 35 children with CAH serum 3 alpha diolG levels
      correlated well with clinical and metabolic status, i.e. 17OHP serum levels. In
      summary, we have established percentile curves for 3 alpha diolG levels in
      healthy children and adolescents. We hypothesize that on the basis of our
      reference values the single measurement of serum 3 alpha diolG could serve as a
      means to determine androgen status in children with disorders of puberty and
      sexual development.

PMID- 9186822
TI  - Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: II.
      A study in the infant rat.
AB  - It is generally accepted that growth hormone influences its own secretion by
      modulating the activity of GHRH and SRIF neurons. To investigate if GH feedback
      mechanisms are already operating in the early postnatal life of the rat, we have
      studied in 10-day-old pups the effects of rhGH and rhIGF-I administration on GHRH
      and somatostatin mRNA levels. The same experiment was also performed in pups
      passively immunized with an anti-GHRH antiserum from the day of birth. The latter
      animal model had been previously characterized for presenting reduced levels of
      circulating GH and IGF-I. In control pups, neither rhGH (250 micrograms/kg,
      b.i.d., sc) nor rhIGF-I (150 micrograms/kg, b.i.d., sc) administration induced
      significant changes of GHRH and SRIF gene expression. The passive immunization
      against GHRH induced per se a trend toward an increase and a reduction of GHRH
      and SRIF mRNA levels, respectively. Also in these rats the treatment for 3 days
      with rhGH and rhIGF-I did not further modify the GHRH and SRIF mRNA levels. Based
      on these results, we conclude that in the 10-day-old rat GH feedback mechanisms
      are poorly operative, though a direct ultra-short loop mechanism involving the
      GHRH and SRIF systems seems already operating.

PMID- 9186821
TI  - Effects of GH and IGF-I administration on GHRH and somatostatin mRNA levels: I. A
      study on ad libitum fed and starved adult male rats.
AB  - The individual role played by GH and IGF-I in the regulation of hypothalamic GHRH
      and SRIF gene expression is still object of debate. We have investigated the
      effect of exogenously administered recombinant hGH (rhGH) and recombinant hIGF-I
      (rhIGF-I) in ad libitum fed control and starved rats, the latter an animal model
      which is characterized by low circulating levels of endogenous GH and IGF-I.
      Adult male rats were fed ad libitum (C) or food-deprived (S) for 72 hours; rats
      in either C or S groups were treated with systemic administration of rhGH and
      rhIGF-I for 3 days. GHRH, SRIF and GH mRNA levels were evaluated by Northern and
      slot blot hybridization. Administration of rhGH (250 micrograms/kg/twice daily,
      sc) induced a significant inhibition of GHRH and a significant stimulation of
      SRIF mRNA levels in C rats; GH treatment was, however, ineffective on both
      neuropeptide mRNA levels in the S group. Continuous infusion of rhIGF-I (300
      micrograms/kg/day, sc) induced a significant increase of SRIF levels in both C
      and S rats but did not modify GHRH mRNA levels in either group. In the pituitary,
      GH mRNA levels followed a pattern very similar to that of GHRH. These results
      provide evidence for a direct role of GH in the inhibition of GHRH mRNA levels;
      IGF-I appears more involved in the direct stimulation of SRIF mRNA levels.

PMID- 9186823
TI  - Graves' hyperthyroidism and ophthalmopathy associated with pemphigus vulgaris:
      onset of thyroid autoimmune disease during chronic low-dose glucocorticoid
      therapy.
AB  - A 38-year-old caucasian woman developed typical Graves' hyperthyroidism and
      ophthalmopathy while being chronically treated for pemphigus vulgaris with low
      doses of glucocorticoids capable of effectively controlling skin disease. HLA
      typing showed positivity for DR3 and DR4, suggesting a genetic susceptibility for
      both Graves' disease and pemphigus vulgaris. The apparent contradiction whereby
      thyroid autoimmune disease flared up during therapy with glucocorticoids, known
      for their immunosuppressive effects, may be related to the dose of steroids. It
      is possible that high doses of glucocorticoids, commonly employed in the
      treatment of severe Graves' ophthalmopathy, might indeed suppress the disease,
      whereas the low doses used in this patient might precipitate or aggravate it.

PMID- 9186825
TI  - Ribavirin enhances the efficacy but not the adverse effects of interferon in
      chronic hepatitis C. Meta-analysis of individual patient data from European
      centers.
AB  - BACKGROUND/AIMS: This study aimed to obtain a more precise estimation of the
      efficacy and tolerability of interferon-ribavirin combination therapy for chronic
      hepatitis C. METHODS: A meta-analysis was carried out of individual patient data
      comprising about 90% of the published experience with combination therapy. The
      study was set in four European university-affiliated liver referral centers. A
      total of 186 individuals with chronic hepatitis C who had participated in three
      randomized controlled trials and one open study were selected for the study.
      Fifty-one had received ribavirin monotherapy (1000-1200 mg/day), 37 interferon
      monotherapy (3 MU 3x/week) and 78 interferon-ribavirin combination therapy
      (dosage as for monotherapy) for 6 months. Twenty patients served as controls.
      Follow-up after therapy was 6 months. Data analysis was by the multivariate
      logistical regression method. RESULTS: The primary outcome measure for efficacy
      was the percentage with a sustained response (ALT normalization and HCV RNA
      negativity 6 months after therapy). The sustained response rate was significantly
      higher for interferon-ribavirin combination therapy than for interferon or
      ribavirin monotherapy (odds ratio IFN-Riba vs IFN = 9.8, 95% CI 1.9-50). The
      estimated probability of sustained response following interferon-ribavirin
      combination therapy was 51% for patients without previous IFN therapy, 52% for
      patients with previous IFN therapy and response-relapse, and 16% for previous IFN
      non-responders. No serious adverse events were observed and less than 10%
      withdrew. CONCLUSIONS: The efficacy of interferon-ribavirin therapy appears to be
      enhanced two- to threefold over interferon monotherapy in all major subgroups of
      chronic hepatitis C patients tested. In view of its acceptable toxicity profile,
      interferon-ribavirin combination therapy is a candidate for the new standard
      therapy for chronic hepatitis C.

PMID- 9186826
TI  - Evolution of hepatitis C virus quasispecies in mothers and infants infected
      through mother-to-infant transmission.
AB  - BACKGROUND/AIMS: Two mother-infant pairs (Pair H and P) were studied to determine
      the evolution of hepatitis C virus (HCV) quasispecies. METHODS: Eight clones of
      the hypervariable region of HCV cDNA from the infants' sera sampled at the age of
      3 months, 1, 2, and 3 years and the time-corresponding maternal sample were also
      sequenced. The sequences were analyzed by the nucleotide diversity, substitution
      rate, and phylogenetic studies. RESULTS: HCV quasispecies of the infants were
      more homogeneous than those of their mothers, particularly at the age of 3 months
      (nucleotide diversity, pi = 0.18 x 10(-2)/site in infant H, and 0.22 x 10(
      2)/site in infant P). The nucleotide substitution rate in infants also increased
      as they aged, from 1.2 x 10(-2) to 4.46 x 10(-2)/site/year in infant H, and from
      0.21 x 10(-2) to 4.88 x 10(-2)/site/year in infant P respectively. The nucleotide
      sequence differences between infants and mothers increased from 2.63 x 10(-2) to
      9.06 x 10(-2)/site in Pair H, and from 1.85 x 10(-2) to 5.33 x 10(-2)/site in
      Pair P within 3 years. Phylogenetic studies suggest the infants' initial
      quasispecies were closely related to their mothers', while they evolved
      differently. HCV RNA titer was stable during follow-up and the infants' titer was
      similar to their mothers'. The fluctuations in titer did not correlate with
      nucleotide diversity. CONCLUSIONS: HCV quasispecies evolved differently in each
      individual, even though they were genetically linked. The sequence in infants was
      not a complex as in their mothers.

PMID- 9186824
TI  - Human endometrium as a neuroendocrine tissue: expression, regulation and
      biological roles of endometrial corticotropin-releasing hormone (CRH) and opioid
      peptides.

PMID- 9186827
TI  - Effect of immunosuppression on composition of quasispecies population of
      hepatitis C virus in patients with chronic hepatitis C coinfected with human
      immunodeficiency virus.
AB  - BACKGROUND/AIMS: To study the effects of the immunosuppression caused by the
      reduction of CD4 activity on the composition of hepatitis C virus (HCV)
      populations, we analyzed the number of HCV quasispecies clones and the nucleotide
      diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with
      hemophilia with persistent HCV infection, with or without human immunodeficiency
      virus (HIV). METHODS: The numbers of HCV quasispecies clones were measured by
      fluorescence single-strand conformation polymorphism analysis. Direct sequencing
      was used to analyze the degree of diversity of HVR1. We compared these values
      according to coinfection with HIV, and CD4 counts of patients. RESULTS: There
      were no differences in either the number of HCV clones or the diversity between
      patients with and without HIV coinfection. In HIV coinfected patients the
      diversity decreased in association with the decrease in CD4 count while the
      number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in
      patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a
      CD4 count > or = 50/microliters; it was significantly lower in the former (p =
      0.0002). CONCLUSIONS: A severe reduction in the CD4 count, which is considered to
      cause a decline in the activity of helper T-lymphocytes, induced changes in the
      composition of HCV populations; one or a few quasispecies clones are predominant
      in the HCV population in the serum of individual patients.

PMID- 9186828
TI  - Autoimmune hepatitis type 2 and hepatitis C virus infection: study of HLA
      antigens.
AB  - BACKGROUND/AIMS: Markers for hepatitis C virus are often detectable in patients
      suffering chronic hepatitis with liver-kidney microsomal type 1 antibodies.
      Several authors have suggested that two subsets of those patients can be defined:
      a) hepatitis C virus negative and b) hepatitis C virus positive. The aim of this
      work was to further analyze the possible genetic association, HLA class I and II,
      in these two groups of patients. METHODS: HLA was analyzed in 49 patients. Class
      I was studied using a standard lymphocytotoxicity test and in class II a reverse
      hybridization-based test for DRB1 typing and PCR-SSO for DQB1 typing were used.
      Sixty healthy Spanish subjects and 39 chronic hepatitis C subjects without anti
      LKM1 antibodies were used as control groups for the "a" and "b" subsets,
      respectively. RESULTS: No significant association was found with class I
      specificities in either group. DQB1 typing showed a very significant increase of
      DQ2 in the "a" group (93.3% vs. 48%; RR = 15; Pc = 0.0025), and DRB1 typing from
      the "b" group revealed a high association with DR7 (82.3% vs. 43.6%; RR = 6; Pc =
      0.0086). CONCLUSIONS: Our studies revealed a strong association with DQ2 for the
      "a" group and for the first time an extremely high association with DR7 antigen
      for the "b" subset. Hence it is possible to establish a different genetic profile
      in these two patient groups.

PMID- 9186830
TI  - Evaluation and comparison of different hepatitis C virus genotyping and
      serotyping assays.
AB  - BACKGROUND/AIMS: Evidence that the geno/subtype of hepatitis C virus (HCV) is
      predictive of the response to interferon-alpha therapy suggests that typing
      methods are clinically useful. In the present study, HCV isolates obtained from
      74 patients with chronic hepatitis C were used to evaluate three genotyping and
      two serotyping assays. METHODS: The reverse hybridization assay and the DNA
      immunoassay are based on immobilized type-specific probes for the 5'-noncoding
      and the core region, respectively. A third genotyping assay utilized type
      specific primers for amplification of the core region. Serotyping assays detect
      type-specific antibodies of the nonstructural-4 region (enzyme immunoassay) or of
      the core and nonstructural-4 region (recombinant immunoblot assay). Gold standard
      geno/subtyping of HCV isolates was performed by sequence and phylogenetic
      analysis of the nonstructural-5B region. RESULTS: All genotyping systems
      amplified the respective target region of the HCV genome with high sensitivity.
      The reverse hybridization assay and the DNA immunoassay correctly identified HCV
      1, -2, and -3. The DNA immunoassay misinterpreted all HCV-4 isolates as HCV-4 and
      -5 coinfection. In the type-specific amplification assay, coinfections of
      subtypes HCV-1a and HCV-3a with HCV-1b could not be excluded. The reverse
      hybridization assay misinterpreted 1/14 HCV-1a isolates as HCV-1h, and vice versa
      3/36 HCV-1b isolates as HCV-1a. Furthermore, differentiation between HCV-2a and 
      2c was not possible using this assay. The DNA immunoassay correctly identified
      all HCV subtypes. The serotyping assays, recombinant immunoblot assay and enzyme
      immunoassay identified HCV-1, -2, and -3 in 93% and 89% of cases, respectively.
      HCV-4, however, could only be recognized by the enzyme immunoassay. CONCLUSIONS:
      The reverse hybridization assay and the DNA immunoassay specifically identified
      HCV genotypes 1, 2, and 3, while crossreactivity occurred in the primer-specific
      amplification assay. The DNA immunoassay achieved the best performance in HCV
      subtyping. Both serotyping systems correctly identified HCV-1, -2, and -3 in
      about 90% of cases, but lack the possibility of subtyping.

PMID- 9186829
TI  - Frequency and significance of antibodies to P450IID6 protein in Japanese patients
      with chronic hepatitis C.
AB  - BACKGROUND/AIMS: The aims of the current study were to assess the frequency and
      the significance of antibodies to cytochrome P450IID6 protein (anti-P450IID6) in
      various diseases among Japanese patients. METHODS: Sera from 541 patients were
      tested by indirect immunofluorescence, and the specificity of anti-P450IID6 was
      ascertained by either enzyme immunoassay (ELISA) or Western blot using
      recombinant antigen or rat liver microsomes. RESULTS: Anti-P450IID6 was found in
      only 6 of 235 patients (2.6%) with chronic active hepatitis (CAH) positive for
      hepatitis C virus (HCV) antibody and quantitative HCV-RNA with genotypes II and
      IV. The predominant epitopes on immunoblots were 66 and 50KD, a 10KD band being
      the newly underfined microsomal antigen. Even in the patients negative for
      autoantibodies to nuclear antigens (ANA) by routine indirect immunofluorescence
      test, various ANA were detected by the newly developed recombinant ELISA. These
      patients were younger, with lower gamma-globulin and IgG levels than patients
      with autoimmune hepatitis. Three of five patients with anti-P450IID6 responded
      well to interferon therapy and one received prednisone when interferon was
      ineffective. Interestingly, only this patient was diagnosed as definite
      autoimmune hepatitis according to the criteria proposed by the International
      Autoimmune Hepatitis Group (IAHG). The other five patients who did not satisfy
      the IAHG criteria might be considered as CAH-C with autoimmune features. No
      autoimmune hepatitis patients positive for anti-P450IID6 were identified in the
      current study, indicating that the variant is very rare in Japan. CONCLUSIONS:
      Anti-P450IID6 in CAH-C patients in Japan is not as rare as expected. Anti
      P450IID6 among Japanese patients has uncertain significance and precludes further
      characterization of CAH-C with autoimmune features, which might require
      interferon therapy.

PMID- 9186831
TI  - Auxiliary partial orthotopic liver transplantation for acute liver failure.
AB  - BACKGROUND/AIMS: Auxiliary partial orthotopic liver transplantation holds
      potential advantages over conventional orthotopic liver transplantation, but
      experience with the technique in acute liver failure is limited. METHODS: We
      describe our initial experience in seven patients (4 men, 3 women; mean age 28,
      range 14-35 years) with acute liver failure (paracetamol 3, non A-E 2, autoimmune
      1, Ecstasy 1) who fulfilled criteria for emergency transplantation.
      Preoperatively, the median international normalised ratio was seven (range 3.4
      15), with a creatinine of 123 microM (51-389 microM) and bilirubin 320 microM (61
      572 microM). The reasons for performing an auxiliary transplant were the
      patients' young age and stable preoperative condition (n = 5), or a significant
      psychiatric history precluding conventional transplantation (n = 2). RESULTS: All
      patients received blood group-matched left (n = 2) or right (n = 5) auxiliary
      grafts. Median duration of surgery was 8.5 h (7.3-10 h), with blood loss of 8.3
      litres (4.6-14.6 litres). Post-transplant, the international normalised ratio and
      aspartate aminotransferase fell progressively in all patients, with median values
      at day 7 of 1.4 (1.0-2.4) and 108 IU/1 (78-910 IU/1). Three patients died from
      sepsis within the first postoperative month. At 2 weeks, four of six patients had
      partial regeneration of the native liver, which became complete in two of the
      survivors by 1 year. CONCLUSIONS: Although patient selection remains poorly
      defined, auxiliary partial orthotopic liver transplantation in acute liver
      failure is technically feasible and, in some patients, allows native liver
      regeneration and eventual immunosuppression withdrawal.

PMID- 9186832
TI  - The pharmacokinetics of octreotide in cirrhosis and in healthy man.
AB  - BACKGROUND/AIM: The aim of the study was to evaluate the pharmacokinetics of
      octreotide in patients with cirrhosis compared to healthy volunteers. METHODS:
      Seventeen patients with cirrhosis and nine normals received an intravenous bolus
      of octreotide (0.75 microgram/kg), followed by a continuous infusion of 0.75
      microgram.kg-1.h-1 for 12 h. Eight patients were decompensated with ascites,
      while nine were without signs of decompensation. Serum octreotide levels were
      followed by blood sampling during the infusion period and for 24 h afterwards.
      RESULTS: The average clearance (+/-SEM) was 151 +/- 15 ml/min in normals compared
      to 102 +/- 9 (p < 0.05) and 105 +/- 9 (p < 0.05) in patients with compensated and
      decompensated cirrhosis, respectively. The average area under the serum
      octreotide curve was significantly increased by 53% (p < 0.05) in decompensated
      and 46% (p < 0.05) in compensated cirrhosis compared to healthy volunteers, while
      no difference was observed between the groups with cirrhosis. This difference was
      also reflected by an increased maximum serum concentration during the infusion
      period of 9797 +/- 580 ng/l in the patients with cirrhosis compared to 7081 +/-
      547 ng/l (p = 0.006) in normals. The serum half-life for the beta-phase (T1/2
      beta) was 165 +/- 26 min in normals, 200 +/- 21 min in the compensated and 216 +/
      26 min in the decompensated group (NS). The volume of distribution (Vd beta)
      showed no difference between the three groups. Because of the slow equilibration
      between plasma and ascitic fluid in decompensated cirrhosis, the calculated
      clearance may have been overestimated and T1/2 beta and Vd beta underestimated in
      these patients. CONCLUSIONS: The present study demonstrates that the
      pharmacokinetics of octreotide in cirrhosis is substantially different from that
      found in normals.

PMID- 9186833
TI  - Effect of octreotide on systemic, central, and splanchnic haemodynamics in
      cirrhosis.
AB  - BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in
      the splanchnic and systemic haemodynamics, and subsequent complications, such as
      bleeding from oesophageal varices, have led to the introduction of long-acting
      somatostatin analogues in the treatment of portal hypertension. However, reports
      on the splanchnic and systemic effects of octreotide are contradictory and
      therefore the aim of the present study was to assess the effects of continuous
      infusion of octreotide on central and systemic haemodynamics, portal pressures,
      and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver
      vein catheterisation. Portal and arterial blood pressures were determined at
      baseline and 10, 30, and 50 min after a bolus injection of octreotide 100
      micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1
      h. Hepatic blood flow, cardiac output, central and arterial blood volume, and
      central circulation time were determined at baseline and 50 min after the start
      of the octreotide infusion. RESULTS: The mean arterial blood pressure increased
      during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The
      central and arterial blood volume (-16%, p < 0.005) and the central circulation
      time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the
      cardiac output did not change significantly. The hepatic venous pressure gradient
      and the hepatic blood flow did not change significantly at any time after
      infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal
      pressure or hepatic blood flow, whereas it may further contract the central blood
      volume and thereby exert a potentially harmful effect on central hypovolaemia in
      patients with cirrhosis. However, these early effects do not exclude the
      possibility that administration of longacting somatostatin analogues over a
      longer period may have a beneficial effect.

PMID- 9186834
TI  - Endoscopic sclerotherapy versus variceal ligation in the long-term management of
      patients with cirrhosis after variceal bleeding. A prospective randomized study.
AB  - BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal
      varices prevents rebleeding in patients with cirrhosis surviving an acute
      variceal bleeding episode. However, this treatment is associated with a
      substantial complication rate. Endoscopic band ligation is a newly developed
      technique in an attempt to provide a safer alternative. The aim of this study was
      to compare the efficacy and safety of injection sclerotherapy versus variceal
      ligation in the management of patients with cirrhosis after variceal haemorrhage.
      METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal
      variceal bleeding were studied. After initial control of haemorrhage by
      sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37
      to ligation. Both procedures were performed under midazolam sedation at intervals
      of 7-14 days until all varices in the distal oesophagus were eradicated or were
      too small to receive further treatment. RESULTS: The eradication of varices
      required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with
      sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was
      similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The
      proportion of patients remaining free from recurrent bleeding against time was
      significantly higher in the ligation group as compared to the sclerotherapy group
      (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the
      ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The
      mortality rate was similar in both groups (20% and 21%, respectively).
      CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term
      management of patients with cirrhosis after variceal haemorrhage which was
      initially controlled with sclerotherapy.

PMID- 9186835
TI  - Mast cells distribution in human liver disease and experimental rat liver
      fibrosis. Indications for mast cell participation in development of liver
      fibrosis.
AB  - BACKGROUND/AIMS: The development of liver fibrosis due to chronic liver diseases
      is thought to be mediated by inflammatory cells releasing fibrogenic mediators
      that activate fat-storing cells (Ito-cells). Recently, the involvement of mast
      cells in fibrogenesis has been suggested. We studied the distribution of these
      cells in normal human liver and human nonfibrotic and fibrotic liver disease as
      well as in normal rat liver and acutely and chronically injured rat liver (CCl4
      model). METHODS: Mast cells were identified by histochemical and
      immunohistochemical methods. The immunoreactivity of liver and comparatively of
      rat peritoneal mast cells to the serpins alpha1-antitrypsin, alpha1
      antichymotrypsin and antithrombin III was also studied. RESULTS: In normal human
      and rat liver, mast cells were rarely found in portal tracts, and there was no
      change in cell numbers in nonfibrotic human or acutely injured rat livers. In
      contrast, cirrhotic human and rat livers contained numerous mast cells in the
      portal tracts and the fibrous septa. They exhibited strong immunoreactivity to
      the serpins, as did rat peritoneal mast cells. CONCLUSIONS: The results indicate
      that in the late stages of liver fibrogenesis, mast cells may be involved by
      displaying protease inhibitory activity in the fibrotic septa.

PMID- 9186836
TI  - Significance of tumor vascularity as a predictor of long-term prognosis in
      patients with small hepatocellular carcinoma treated by percutaneous ethanol
      injection therapy.
AB  - BACKGROUND/AIMS: We estimated the significance of the vascularity of small
      hepatocellular carcinoma (HCC) as a predictor of long-term prognosis in patients
      treated with percutaneous ethanol injection therapy (PEIT/PEI). METHODS: Fifty
      four patients who have been followed-up in our hospital and who had HCC less than
      20 mm in diameter were observed for 199 to 2074 days. Hepatic angiography
      (digital subtraction angiography; DSA and ultrasound angiography with
      intraarterial CO2 microbubbles; USAG) was performed before treatment in all
      cases, and the vascularity of the tumor was clinically evaluated. The survival
      rate was analyzed according to this vascularity. RESULTS: Of the 54 tumors, 24
      had tumor stain on DSA, while 30 did not, and 38 showed enhancement on USAG,
      while 16 did not. The 3- and 5-year survival rates were 48.7 and 34.1% and 89.7
      and 69.7% of patients with negative staining HCC (p = 0.0723). The rates were
      48.6 and 36.7%, respectively, of patients with positive enhancement HCC on USAG,
      and both rates were 85.7% of patients with negative enhancement HCC (p = 0.0231).
      CONCLUSIONS: Tumor vascularity will play a role in the long-term prognosis of
      these patients with small HCC when they are treated with PEIT/PEI.

PMID- 9186837
TI  - In vitro effects of cholecystokinin fragments on human gallbladders. Evidence for
      an altered CCK-receptor structure in a subgroup of patients with gallstones.
AB  - BACKGROUND/AIM: This study addresses cholecystokinin (CCK)-receptor alterations
      in stone-diseased and stone-free human gallbladders using different CCK
      fragments. METHODS: Serosa-free muscle strips were mounted in a modified Krebs
      Henseleit-solution of 37 degrees C and aerated with carbogen. The following
      concentrations of CCK-fragments (CCK 26-33, N-Acetyl CCK 27-33 sulf., CCK 26-29
      sulf., CCK 25-33 sulf.) were achieved: 0.1 nmol, 0.5 nmol, 2 nmol, 10 nmol, 100
      nmol. RESULTS: Stone-diseased gallbladders were classified into two groups based
      on their in vitro reaction to CCK 26-33 (CCK-octapeptide). Muscle strips not
      contracting below 10 nmol were assigned to the subcontractor group.
      Histologically scarification, necrosis and signs of severe inflammation of the
      mucosa were seen in 76.9% of this group. Those starting contractions at 0.1 nmol
      (like the control group) were called the contractor group. This group had a
      shallow mucosa and mild inflammatory signs in 54.5%. The sub-contractor group
      showed higher spontaneous phasic activity at lower tonic activity than the
      contractor and control groups. In the sub-contractor group CCK 27-33 caused
      several times higher contractions than all other fragments. A maximal contraction
      level in the contractor and control groups was reached by CCK 25-33. CONCLUSIONS:
      This striking effect of CCK 27-33 in the sub-contractor group favors the view of
      CCK-receptor structural alteration in a subgroup of patients with
      cholecystolithiasis.

PMID- 9186838
TI  - Evidence for secretory coupling of phosphatidylcholine molecular species to
      cholesterol in rat bile.
AB  - BACKGROUND/AIMS: Hepatocytes secrete cholesterol into bile within lipid vesicles
      of selected phosphatidylcholines, mainly palmitoyl-linoleoyl
      phosphatidylcholines, palmitoleoyl-oleoyl-phosphatidylcholines and palmitoleoyl
      arachidonyl-phosphatidylcholines, which could in part determine the secreted
      amount of cholesterol. AIMS: To study whether increased secretion of cholesterol,
      as caused by manipulation of cholesterol synthesis rate, changes the composition
      of phosphatidylcholines secreted in bile. METHODS: Livers from control rats
      (Control), rats fed pravastatin for 7 days (Pravastatin) and livers isolated 5-7
      or 8-11 hours after pravastatin had been withdrawn (Rebound5-7h; Rebound8-11h)
      were isolated perfused during infusion of taurocholic acid (400 nmol/min/100 g
      rat), to study biliary secretion of bile salts, cholesterol and
      phosphatidylcholine molecular species. RESULTS: Bile salt secretion rate was
      similar in all four groups, secretion of cholesterol and phosphatidylcholines was
      similar in Control and Pravastatin. With duration of pravastatin withdrawal the
      secretion rates of phosphatidylcholine and cholesterol progressively increased by
      +38% and +122% in Rebound5-7h and by +70% and +300% in Rebound8-11h (vs Control),
      respectively. In parallel, the secretion rates of palmitoleoyl-oleoyl- and
      palmitoleoyl-arachidonyl-phosphatidylcholines rose up to sixfold and twofold,
      respectively, while the secretion rate of palmitoyl-linoleoylphospatidylcholines
      remained constant. The secretion rate of cholesterol was correlated (p < 0.01)
      with the secretion rates of palmitoleoyl-oleoyl-phosphatidylcholines (r = 0.83)
      and palmitoleoyl-arachidonyl-phosphatidylcholines (r = 0.81). Bilirubin ditaurate
      or taurodehydrocholate reduced (p < 0.05) biliary secretion of
      phosphatidylcholines (-33%; -72%) without changes in
      cholesterol/phosphatidylcholine secretory ratio or phosphatidylcholine species.
      CONCLUSIONS: The secretion of the major molecular species of phosphatidylcholine
      in bile could be coregulated with the amount of cholesterol destined for biliary
      secretion.

PMID- 9186839
TI  - TGF-beta-mediated hepatocellular apoptosis by rat and human hepatoma cells and
      primary rat hepatocytes.
AB  - BACKGROUND/AIMS: Primary cultures of rat hepatocytes, rat (FAO) and human (HepG2)
      hepatoma cells were studied by immunocytochemistry for expression of transforming
      growth factor (TGF)-beta, for the release of TGF-beta into the medium, and
      generation of hepatocellular apoptosis by the respective cell-conditioned media.
      METHODS/RESULTS: Using the alkaline-phosphatase anti-alkaline-phosphatase
      technique, intense TGF-beta immunostaining was shown in all cell types. The
      cytokine is released almost entirely in the latent form into the culture medium;
      only the FAO-cells had a substantial fraction of bioactive TGF-beta in the native
      (unacidified) culture fluid. Exposure of hepatocytes with the respective cell
      conditioned media in the activated, but not in the native form (except for FAO
      cell media), induced severe detrimental effects as evidenced by: (i) gross
      morphological alterations, (ii) functional impairment (reduction of WST-1 test,
      detachment of cells, lactate dehydrogenase increase in the medium), and (iii)
      generation of apoptosis. The latter phenomenon was confirmed by an increase of
      internucleosomal DNA fragments, positive TUNEL reaction, and intense binding of
      the fluorochrome Hoechst 33342 to fragmented nuclei. All these effects, which
      were mimicked by addition of recombinant human TGF-beta 1, were almost entirely
      antagonized by pre-incubation of the conditioned media with latency associated
      peptide. In contrast to hepatocytes, both types of hepatoma cells were completely
      resistant to the multiple actions of TGF-beta and activated conditioned media.
      CONCLUSIONS: It is concluded that hepatocytes might have the ability to induce
      autocrine, TGF-beta-mediated apoptosis, whereas hepatoma cells, because of their
      TGF-beta resistance, might generate TGF-beta-mediated peritumorous apoptosis of
      hepatocytes in a paracrine way, which could facilitate their expansion in situ.
      Both mechanisms, however, are critically dependent on extracellular TGF-beta
      activation.

PMID- 9186840
TI  - Macrophages from rat livers with micronodular and macronodular cirrhosis differ
      with respect to mediator release and DNA-synthesis.
AB  - BACKGROUND/AIMS: Liver macrophages play an essential role in necro-inflammatory
      liver damage which leads to fibrosis and cirrhosis. The aim of the present study
      was to compare the mediator release and the DNA synthesis of macrophages at an
      early and at a later stage of liver cirrhosis induced by thioacetamide. METHODS:
      Liver macrophages were isolated by an enzymic digestion method, followed by
      elutriation. The release of reactive oxygen species and cytokines, and the
      synthesis of DNA were measured in cultivated cells. RESULTS: The vitality of
      isolated macrophages from cirrhotic livers was always higher than 98%. The total
      yield of macrophages was less in micronodular cirrhotic livers and was markedly
      higher in macronodular cirrhotic livers when compared with age-matched controls.
      The cellular granules measured by sideward light scattering showed a shift to
      larger sizes in macrophages from micronodular cirrhotic livers when compared with
      the controls and the other experimental group. Macrophages from both cirrhosis
      groups exhibited a markedly higher unstimulated and lipopolysaccharide-stimulated
      IL-6 production than the controls. The release of TNF-alpha did not differ
      between controls and the experimental groups. Macrophages from macronodular
      cirrhotic livers produced higher amounts of nitric oxide but less superoxide
      anion radicals than the controls. DNA synthesis was 10-12-fold and 3-10-fold
      higher in macrophages from micronodular and macronodular cirrhotic livers,
      respectively, when compared with the age-matched controls. CONCLUSIONS: The data
      presented provide evidence that it is possible to isolate and to cultivate
      macrophages from livers with high yield and vitality at different stages of
      cirrhogenesis. Our results clearly demonstrate functional differences between
      macrophages from livers with micro- or macronodular cirrhosis; this finding may
      be important for the pathogenesis or perpetuation of the cirrhogenetic process.

PMID- 9186841
TI  - Endothelin-1 induces liver vasoconstriction through both ETA and ETB receptors.
AB  - BACKGROUND/AIMS: We investigated which endothelin receptors mediate the
      vasoconstrictive effects of endothelin-1 on liver circulation. METHODS: An
      isolated perfused rat liver model in recirculation was used. RESULTS: The
      perfusion of 10(-10) M endothelin-1 had no significant influence on the liver
      flow, whereas 10(-9) M endothelin-1 induced significant vasoconstriction, with
      flow dropping from 3.20 +/- 0.34 to 1.48 +/- 0.28 ml. min-1.g-1 liver tissue (p <
      0.01 vs controls). The liver flow was interrupted following the perfusion of 10(
      8) M endothelin-1. Sarafatoxin C and BQ 3020, two agonists of ETB receptor, had
      vasoconstrictive effects in this model. Sarafatoxin C decreased the liver flow in
      a dose-dependent manner, from 3.32 +/- 0.21 to 2.18 +/- 0.20, 1.60 +/- 0.09, and
      1.01 +/- 0.06 ml.min-1. g-1, respectively, with 10(-9) M, 10(-8) M, and 10(-7) M.
      While BQ 123, an antagonist of ETA receptor, or BQ 788, an antagonist of ETB
      receptor, partially reversed the effect of 10(-9) M endothelin-1, the
      simultaneous administration of BQ 123 and BQ 788 completely reversed these
      effects. CONCLUSIONS: These results indicate that the vasoconstrictive effects of
      endothelin-1 on the liver circulation are mediated through both ETA and ETB
      receptors.

PMID- 9186842
TI  - Role of calcitonin gene-related peptide in the vascular system on the development
      of the hyperdynamic circulation in conscious cirrhotic rats.
AB  - BACKGROUND/AIMS: Calcitonin gene-related peptide (CGRP), a potent vasodilator;
      plays an important role in modulating vascular tone, acting as a noncholinergic
      nonadrenergic neurotransmitter. The aim of this study was to assess the role of
      CGRP, present in the vascular system, in the development of the hyperdynamic
      circulation observed in liver cirrhosis. METHODS: Two doses of human alpha-CGRP
      [8-37], a specific antagonist of CGRP, were administered to cirrhotic and
      controls rats. Hemodynamics were evaluated using radioactive microspheres in
      conscious animals. To investigate the arterial depressor effect of exogenous
      CGRP, we constructed a dose-response curve for mean arterial pressure in
      cirrhotic and control rats by administering human alpha-CGRP. RESULTS: The
      administration of high-dose human alpha-CGRP [8-37] (300 nmol.kg body weight
      1.min-1) significantly increased both the mean arterial pressure (21 +/- 2 vs. 13
      +/- 1%, p < 0.01) and total vascular resistance (76 +/- 5 vs. 54 +/- 5%, p <
      0.01) in cirrhotic rats, compared to control rats. The splanchnic hemodynamic
      effects induced by human alpha-CGRP [8-37] were a significant decrease in percent
      change of portal venous inflow -42 +/- 3 vs. -33 +/- 3%, p < 0.05) and a
      significant increase in percent change of splanchnic arterial resistance (110 +/-
      9 vs. 76 +/- 5%, p < 0.01) in cirrhotic rats, compared to control rats. Low-dose
      human alpha-CGRP [8-37] (60 nmol.kg body weight-1. min-1) caused similar
      hemodynamic changes, but the degree of change was much less than for the high
      dose administration. The vascular response to human alpha-CGRP was significantly
      reduced in cirrhotic rats as compared to controls (ANOVA, p < 0.01). Plasma
      concentrations of CGRP were significantly elevated in cirrhotic rats.
      CONCLUSIONS: CGRP in the vascular system was involved in the modulation of
      vasodilatation in rats with liver cirrhosis, as demonstrated by the
      administration of a selective CGRP antagonist and exogenous CGRP.

PMID- 9186843
TI  - Induction of nitric oxide synthase II does not account for excess vascular nitric
      oxide production in experimental cirrhosis.
AB  - BACKGROUND/AIMS: Excess production of nitric oxide (NO) reduces vasoconstriction
      of cirrhotic rat aorta. Expression of the inducible nitric oxide synthase (NOS
      II) in endothelial cells or vascular smooth muscle could account for this, as
      described with endotoxin or lipopolysaccharide (LPS) treatment. Alternatively,
      the endothelial NOS enzyme (NOS III) could be activated by an as-yet undescribed
      mechanism. Here we describe a combined study of the basal release of NO and
      quantitative measurement of the mRNA for NOS II and NOS III from thoracic aorta
      of an animal model of cirrhosis. METHODS: Thoracic aortas of six normal, six
      cirrhotic (secondary biliary cirrhosis) and six intra-peritoneal LPS-treated (15
      mg/kg) rats were removed. Dissected aortic rings were precontracted with
      norepinephrine (NE; 10(-6) M) and relaxed with acetylcholine (Ach; 10(-6) M) with
      or without pre-incubation with the specific NOS inhibitor (L-NNA, 10(-5) M).
      Total RNA was extracted from aorta, reverse transcribed (RT) and used in
      polymerase chain reaction (PCR) amplification with primers specific for NOS II,
      NOS III and beta-actin. PCR products were hybridized with fluorescein labelled
      cDNA probes and the relative intensity on film was analyzed by densitometry.
      RESULTS: Compared to normal, NE caused 32% less contraction in cirrhotic and 43%
      less contraction in LPS-treated aortic rings. This response was corrected to
      normal by L-NNA pre-incubation. All the contracted rings relaxed with Ach. NOS II
      mRNA, was expressed only in LPS-treated aorta and not in aorta from normal and
      cirrhotic rats. NOS III mRNA levels were the same in normal, cirrhotic and LPS
      treated rats: 1176 +/- 170, 1233 +/- 626 and 979 +/- 423, in arbitrary
      densitometry units, respectively. CONCLUSIONS: NO is overproduced by aorta from
      cirrhotic and LPS-treated rats. In LPS-treated rats this could result from
      expression of NOS II, but this was not the case in the cirrhotic rat aorta.
      Comparable amounts of NOS III mRNA suggest that, in cirrhosis, increased activity
      of this enzyme and not increased NOS III expression is responsible for the
      overproduction of NO.

PMID- 9186844
TI  - Effects of long-term administration of octreotide on sodium retention and atrial
      natriuretic peptide in carbon tetrachloride-induced cirrhotic rats.
AB  - BACKGROUND/AIMS: To realize the roles of peripheral vasodilatation and atrial
      natriuretic peptide in the formation of cirrhotic ascites, the effects of long
      term administration of octreotide on carbon tetrachloride-induced cirrhotic rats
      were evaluated. METHODS: Urine sodium excretion, hemodynamics, plasma atrial
      natriuretic peptide levels, renin activities and aldosterone concentrations were
      compared between cirrhotic and control rats (protocol 1); and between octreotide-
      (65 micrograms/kg, twice daily for 10 days, subcutaneously) and placebo-treated
      (5% dextrose) cirrhotic rats (protocol 2). In an in vitro experiment, right
      atrial tissue of cirrhotic rats was incubated with different concentrations of
      octreotide to evaluate the release of atrial natriuretic peptide (protocol 3).
      RESULTS: Cirrhotic rats had significantly lower urine sodium excretion and
      systemic vascular resistance, and significantly higher plasma atrial natriuretic
      peptide levels, renin activities and aldosterone concentrations than control
      rats. Compared with placebo-treated cirrhotic rats, octreotide caused increased
      urine sodium excretion (-10 +/- 4% vs. 13 +/- 8% from baseline values, p < 0.05)
      and systemic vascular resistance (2.6 +/- 0.1 vs. 3.3 +/- 0.3 mmHg.min.100 g.ml
      1, p < 0.05); and decreased plasma atrial natriuretic peptide levels (166.7 +/-
      24.8 vs. 234.0 +/- 19.2 pg/ ml, p < 0.05), renin activities (2.45 +/- 0.49 vs.
      4.36 +/- 0.53 ng.ml-1.h-1, p < 0.01) and aldosterone concentrations (290.2 +/-
      40.0 vs. 483.3 +/- 82.6 pg/ml, p < 0.05). In the in vitro experiment, right
      atrial release of atrial natriuretic peptide of cirrhotic rats was not
      significantly changed when incubated with different concentrations of octreotide.
      CONCLUSIONS: Octreotide ameliorates renal sodium retention and suppresses plasma
      levels of atrial natriuretic peptide of ascitic cirrhotic rats with a novel
      mechanism via, at least partly, the modification of peripheral vascular
      resistance.

PMID- 9186845
TI  - Characterization of glycosaminoglycans in regenerating canine liver.
AB  - BACKGROUND/AIMS: Liver regeneration after partial hepatectomy is accompanied by
      hepatocyte proliferation and alteration of the extracellular matrix.
      Glycosaminoglycans, which are components of the extracellular matrix, interact
      with other matrix components, and are related to hepatocyte growth. The aim of
      this study was to investigate the relationship between hepatocyte proliferation
      and changes in glycosaminoglycan. METHODS: Hepatocyte proliferation and changes
      in glycosaminoglycan were investigated in dogs after 55% partial hepatectomy.
      Hepatocyte mitosis was investigated by immunohistochemistry using anti
      proliferating cell nuclear antigen antibody. The amount of glycosaminoglycan was
      determined by the carbazole-sulfuric acid method. We used a new method for
      analysis of glycosaminoglycan chains, involving endo-beta-xylosidase digestion
      and fluorescence labelling, to investigate the components of glycosaminoglycan.
      RESULTS: Hepatocyte mitosis was increased after hepatectomy, reaching a peak at
      postoperative day 7. The total amount of hepatic glycosaminoglycan reached a
      maximum at 1 to 2 weeks afer hepatectomy, and the ratio of the components showed
      a concomitant change, the amount of heparan sulfate increasing, and that of
      chondroitin sulfate/dermatan sulfate decreasing. Increased heparan sulfate has
      shorter chains at 1 to 2 weeks after hepatectomy. CONCLUSIONS: These results
      suggest that the transient changes in heparan sulfate with a decreased chain
      length and chondroitin sulfate/dermatan sulfate and observed during liver
      regeneration are associated with hepatocyte proliferation.

PMID- 9186846
TI  - Leucine metabolism in partially hepatectomized rats.
AB  - BACKGROUND/AIMS: We hypothesized that the decrease in plasma branched-chain amino
      acids (i.e. valine, leucine and isoleucine) and the increase in the oxidized
      leucine fraction demonstrated in cirrhotic rats in our previous study were caused
      by the reduced liver cell mass. In the present study we have evaluated the
      influence of the loss of a substantial amount of the hepatic tissue on changes in
      leucine metabolism. METHODS: A two-thirds partial hepatectomy (PH) was performed
      in male Wistar rats, weighing 210-250 g. Sham-operated rats served as controls.
      Whole-body leucine kinetics and ketoisocaproate oxidation rates in the isolated
      perfused liver were investigated using continuous infusion of [1-14C]leucine and
      alpha-keto[1-14C]ketoisocaproate at 0 h, 24 h and 72 h after surgery. All groups
      were compared by analysis of variance, and differences were considered
      significant at the p < 0.05 level. RESULTS: A significant decrease in the sum of
      branched-chain amino acids in blood plasma was observed at 24 h after PH. The
      decrease in whole-body leucine utilization in protein synthesis observed at 24 h
      after PH was associated with a decrease in protein synthesis in the gastrocnemius
      muscle, in the small intestine and in the liver remnant (although protein
      synthesis per mg of liver protein was higher than in sham-treated animals). In
      contrast, the rate of whole-body leucine oxidation increased immediately after PH
      (PH: 4.5 +/- 0.7 vs. sham: 2.4 +/- 0.4; mumol .100 g b.w.-1.h-1). As a result of
      the opposite changes in protein synthesis and leucine oxidation, marked increases
      in oxidized leucine fraction were observed immediately (14.6 +/- 1.5%) and 24 h
      (15.1 +/- 1.6%) after PH in comparison to the sham-treated rats (7.1 +/- 0.8%).
      In isolated perfused livers of PH rats, an increase in ketoisocaproate oxidation
      per liver weight unit was observed at 24 h and 72 h in comparison to the sham
      group. The loss of liver capacity for ketoisocaproate oxidation was restored at
      72 h after PH, although the liver weight did not reach the preoperative value.
      CONCLUSIONS: We conclude that the loss of hepatic tissue results in an increase
      in leucine oxidized fraction that is caused by both a decrease in protein
      synthesis and an increase in leucine oxidation. Both the liver remnant and the
      extrahepatic tissues are involved in this response.

PMID- 9186848
TI  - Images in hepatology. Manifestation of hepatocellular carcinoma as osteolytic
      acrometastasis.

PMID- 9186847
TI  - Hepatitis B virus polymerase mutations during antiviral therapy in a patient
      following liver transplantation.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate possible resistance
      mutations which arose in the polymerase gene of hepatitis B virus (HBV) in a
      patient with severe recurrent HBV infection following liver transplantation. The
      patient's management included antiviral chemotherapy for almost 4 years
      comprising ganciclovir, foscarnet and famciclovir. In the last 2.5 years of
      famciclovir treatment, an increase in serum HBV DNA levels and a reduced
      sensitivity of the virion-associated DNA polymerase to penciclovir triphosphate
      were observed. METHODS: The viral polymerase gene and X gene were sequenced from
      serum samples collected at representative time intervals covering the entire
      treatment period. RESULTS: No mutations were detected in the X gene. Three
      nucleotide mutations, each of which resulted in an altered amino acid sequence,
      were detected in the polymerase gene after 816 days of total antiviral therapy
      (370 days of famciclovir). Two of these mutations were detected by direct
      sequencing and the third was detected after cloning and was present in 10% of the
      clones. All three mutations occurred in "region B" of RNA-dependent DNA
      polymerases. The HBV polymerase has similarities to both RNA and DNA polymerases.
      These mutations in the HBV polymerase gene were located in a similar area to the
      penciclovir-induced mutations observed in the herpes simplex virus DNA polymerase
      gene. CONCLUSIONS: Three mutations within the HBV polymerase gene were detected
      which were associated with a reduced penciclovir sensitivity.

PMID- 9186849
TI  - Ultrasound-guided biopsy for the diagnosis of hepatocellular carcinoma--a study
      based on 420 patients.

PMID- 9186850
TI  - Bile acid kinetics and biliary lipid composition in cystic fibrosis.

PMID- 9186851
TI  - Role for CD4 positive T cell response in the pathogenesis of hepatitis B.

PMID- 9186852
TI  - HCV and hypogammaglobulinemia.

PMID- 9186853
TI  - Report of the editor. July, 1984-June, 1997.

PMID- 9186854
TI  - The renal risks of smoking.

PMID- 9186855
TI  - Atherosclerosis and arteriosclerosis in chronic renal failure.

PMID- 9186856
TI  - Cytochrome P450-derived renal HETEs: storage and release.
AB  - We have established an assay based on gas chromatography-mass spectrometry to
      profile and quantitate endogenous cytochrome P450 monooxygenase (P450)
      hydroxyeicosatetraenoic acids (HETEs) exiting the isolated perfused rabbit kidney
      in response to hormonal stimulation. In response to angiotensin II (Ang II) P450
      derived HETEs (16-, 17-, 18-, 19- and 20-) are released from the isolated Kreb's
      perfused rabbit kidney. Ang II produced a several-fold increase in the levels of
      P450-HETEs above basal levels in both urinary (such as for 20-HETE from 0.93 +/-
      0.7 to 2.31 +/- 0.9 ng/min) and venous (from 0.1 +/- 0.05 to 0.3 +/- 0.05 ng/min)
      effluents. However, inhibition of P450, which reduced basal release, did not
      prevent Ang II-induced release of P450-AA products from the rabbit kidney; for
      example, urinary 20-HETE in the presence of 17-ODYA (1 microM) was undetectable
      and increased to 0.93 +/- 0.4 ng/min with Ang II and venous 20-HETE increased
      from 0.06 +/- 0.03 to 0.24 +/- 0.07 ng/min. Similar results were obtained with
      clotrimazole (1 microM). As 16-, 18-, 19- and 20-HETEs are vasodilators in the
      rabbit kidney and 16- and 17-HETEs inhibit proximal tubular ATPase activity, we
      investigated their possible sites of esterification. Cortical and medullary
      lipids were extracted, separated by HPLC and P450-HETEs quantitated following
      alkaline hydrolysis. The P450-HETEs were incorporated into both neutral lipids
      (NL) and phospholipids [phosphatidylethanolamine (PE), phosphatidylinositol (PI),
      phosphatidylserine (PS) and phosphatidylcholine (PC)]. However, the assignment of
      a HETE to a specific phospholipid pool must be regarded as tentative as the
      appropriate standards containing P450-HETEs in the Sn-2 position (such as 20-HETE
      PF., 20-HETE-PC, etc.) were not available. Esterified HETEs were found in larger
      quantities in the cortex as compared to the medulla (34.40 +/- 1.12 versus 22.76
      +/- 0.53 ng/g). The PI fraction in the cortex yielded the largest quantity of
      HETEs and the PC fraction the lowest. In the medulla, the largest quantities of
      esterified HETEs were found in neutral lipids and only slightly lesser amounts in
      PE and PI. Esterified 18-HETE was localized only to the NI fraction. This
      fraction also contained the other HETEs, 19- and 20-HETE being the most abundant.
      Notably only 16- and 17-HETE were present in PF, whereas, 19- and 20-HETE were
      also present in PI, PS and PC. Thus, P450-HETEs, like EETs are stored in the
      kidney and are, presumably, subject to release by peptide activation of
      acylhydrolases.

PMID- 9186857
TI  - Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular
      cells.
AB  - The adverse effects of acute renal ischemia are partly mediated through an
      infiltration of inflammatory cells into the tubulointerstitium. The expression of
      adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) by resident
      renal cells (endothelial cells and tubular cells) may facilitate this process. We
      investigated whether hypoxia stimulates the expression of ICAM-1 by cultured
      human proximal tubular cells (HPTC). Hypoxic culture conditions (PO2 < 4 kPa)
      stimulated the expression of ICAM-1 by HPTC in a time-dependent manner (P <
      0.0001) as demonstrated by quantitative flow cytometry analysis. Quantitative PCR
      demonstrated an increase in ICAM-1 transcription. Re-oxygenation of tubular cells
      did not increase ICAM-1 expression further. TNF alpha concentration in culture
      supernatants increased with hypoxia, but blocking experiments demonstrated that
      TNF alpha was not implicated in hypoxia-induced expression of ICAM-1.
      Furthermore, the cytokines IL-6 and IL-1 beta were not involved, but the effect
      of hypoxia was blocked by PDTC, an antioxidant that may inhibit the activation of
      the transcription factor NF-kappa B. These data demonstrate that hypoxia is a
      stimulus that induces the synthesis and expression of the adhesion molecule ICAM
      1, presumably via the activation of NF-kappa B.

PMID- 9186858
TI  - Phosphate depletion diminishes Mg2+ uptake in mouse distal convoluted tubule
      cells.
AB  - Hypophosphatemia caused by phosphate depletion is associated with renal magnesium
      wasting. The cellular mechanisms of phosphate depletion were investigated in an
      immortalized mouse distal convoluted tubule (MDCT) cell line. Intracellular free
      Mg2+ concentration. [Mg2+]i was determined by microfluorescence. Mg2+ transport
      was assessed as a function of change in [Mg2+]i with time following placement of
      Mg(2+)-depleted cells into a buffer containing 1.5 mM magnesium. The uptake rate
      of Mg2+ into Mg(2+)-depleted cells cultured in normal phosphate, 1.0 mM, was 175
      +/- 21 nM/second. Depletion of phosphate in the culture media was associated with
      a significant decrease in Mg2+ uptake, which was dependent on the degree of
      phosphate depletion and on the time cultured in phosphate-deficient media. Cells
      cultured for 16 hours in 0.3 mM and 0 mM phosphate possessed Mg2+ uptake rates of
      105 +/- 18 nM/second and 15 +/- 12 nM/second, respectively. Diminished Mg2+
      uptake was rapidly induced following placement in low phosphate and was fully
      reversed following readdition of phosphate to the culture media. The effects of
      phosphate depletion on Mg2+ uptake was post-translational in nature as fully up
      regulated MDCT cells with maximal Mg2+ uptake was associated with a rapid
      decrease (within 30 min) in Mg2+ transport when placed in phosphate-deficient
      media. Although Mg2+ uptake is altered by the transmembrane voltage, diminished
      Mg2+ uptake associated with phosphate depletion was not dependent on changes in
      membrane voltage. Further, it was not associated with a sustained increase in
      intracellular Ca2+ concentration. Chlorothiazide, probably through
      hyperpolarization of the plasma membrane, stimulates Mg2+ uptake in normal. 283
      +/- 23 nM/second, and phosphate-depleted cells, 203 +/- 29 nM/second, but failed
      to entirely correct the defective transport. These studies demonstrate that
      magnesium wasting associated with hypophosphatemia and phosphate depletion is
      due, in part, to diminished Mg2+ transport in the distal convoluted tubule. The
      evidence is that the actions of phosphate deficiency are through alterations of
      Mg2+ transport across the luminal membrane of the distal convoluted tubule cell.

PMID- 9186859
TI  - Estrogen effects on the renal handling of calcium in the ovariectomized perfused
      rat.
AB  - Estrogen deficiency is a major cause of bone loss in women but the mechanism is
      unclear. The ovariectomized (OVX) rat is a well recognized model for post
      menopausal osteoporosis. In this study we have examined the effects of OVX and
      estrogen replacement in the OVX rat on the renal handling of calcium in response
      to alterations in the calcium load in the perfused rat. The interaction of
      estrogen administration and parathyroid hormone (PTH) was also examined in the
      OVX, parathyroidectomized (PTX) rat. Calcium or EDTA was infused into sham or OVX
      rats to obtain a range of filtered calcium loads. The excretion of calcium, was
      compared to the filtered load for the data from both perfusions indicating a
      lower calcium (P = 0.006) and sodium (P = 0.009) excretion in the OVX rat. A
      similar result was seen in the OVX rat replaced with 20 micrograms of estrogen
      valerate 48 and 24 hours prior to perfusion with calcium excretion being greater
      with estrogen administration (P = 0.005) compared to vehicle alone. This was not
      observed in the parathyroidectomized rat. Correlations between sodium and water
      reabsorption and calcium and sodium reabsorption during perfusion indicate that
      the results of OVX were due primarily to proximal tubule effects. Prior to the
      perfusion experiment PTH (sham vs. OVX pmol/liter, mean +/- SD; 20 +/- 6 vs. 18
      +/- 4) and calcitriol (128 +/- 85 vs. 97 +/- 74) were similar in both groups,
      indicating that the results were not dependent on calcitropic hormone effects. It
      is concluded that, in the perfused rat, OVX results in decreased excretion of
      calcium and sodium as a result of estrogen effects on the renal proximal tubule,
      an effect dependent on PTH. This effect is opposite to that found in
      postmenopausal women, perhaps due to the high filtered load of calcium used in
      the experimental design and species differences in the relative importance of
      proximal versus distal calcium handling.

PMID- 9186860
TI  - Expression of fibroblast growth factors and their receptors in rat glomeruli.
AB  - Fibroblast growth factors (FGFs) regulate cell proliferation and differentiation,
      and are also important regulators of extracellular matrix. They are among the
      most potent angiogenic factors known. Evidence suggests the FGFs play a role in
      glomerular development and pathology. The aim of the present study was to
      determine whether FGF-1 (acidic FGF) and FGF-2 (basic FGF) and their receptors
      (FGFRs) were expressed in normal adult rat glomeruli, using reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemistry. For RT-PCR studies,
      the kidneys of 200 g female Sprague-Dawley rats were perfused with buffer and
      glomeruli isolated using conventional sieving techniques followed by
      micropipetting. FGF-1 and FGF-2 were expressed in cortex and in glomeruli. All
      seven receptor isoforms assayed (FGFR1, 2 and 3 IIIb and IIIc splice variants,
      and FGFR4) were expressed in whole cortex. However, only the IIIc variants and
      FGFR4 were expressed in glomeruli. The relative levels of glomerular expression
      of these isoforms were determined using a semiquantitative RT-PCR assay using
      primers designed against three transmembrane regions; FGFR1 (100%); FGFR2 (0.1%);
      and FGFR4 (6%). Immunohistochemistry revealed specific immunostaining for all
      four FGFRs within glomeruli. The differential expression pattern of FGFR isoforms
      between glomeruli and whole cortex, and the mutually exclusive nature of the
      expression of IIIc but not IIIb isoforms within glomeruli, indicates that FGFR
      expression and thereby FGF activity is tightly regulated in glomeruli. These
      findings have important implications for the roles of the FGFs in glomerular
      health and disease.

PMID- 9186861
TI  - Agonistic anti-Fas antibodies induce glomerular cell apoptosis in mice in vivo.
AB  - Recent studies suggest that apoptotic cell death regulates the cell complement in
      glomerular diseases. However, little is-known about the factors that promote
      glomerular cell apoptosis. Activation of the Fas receptor by the Fas ligand or
      agonistic antibodies triggers apoptosis in some cell types that express Fas.
      Cultured human mesangial cell are among the cells that undergo apoptosis upon Fas
      activation, but it is unclear whether mesangial cells are sensitive to death
      induced by Fas in vivo. We have now explored the role of Fas in experimental
      glomerular injury. Murine mesangial cells in culture express fas and undergo
      apoptosis when stimulated with the Jo2 agonistic anti-Fas mAb. A fas mRNA
      transcript is present in normal murine kidney and freshly isolated glomeruli.
      Balb-c mice developed hematuria and proteinuria within 24 hours of the
      intraperitoneal injection of 10 micrograms Jo2 anti-Fas mAb. In addition to liver
      cell apoptosis, glomerular cell apoptosis and mesangial cell depletion were
      evident in the kidney at three hours and more pronounced at 24 hours. Glomerular
      and liver injury were not prevented by decomplementation. These data suggest that
      Fas activation in vivo by specific antibodies induces glomerular and mesangial
      cell apoptosis in mice.

PMID- 9186862
TI  - Tyrosine phosphorylation in DNA damage and cell death in hypoxic injury to LLC
      PK1 cells.
AB  - Hypoxia is classically considered to result in a necrotic form of cell injury. We
      have recently demonstrated a role of endonuclease activation, considered a
      feature of apoptosis, in DNA damage and cell death in chemical hypoxic injury to
      renal tubular epithelial cells (LLC-PK1 cells). Tyrosine phosphorylation has been
      implicated to be involved in cell signaling pathway leading to cell growth,
      proliferation, and apoptotic death. However, a role of tyrosine phosphorylation
      as a signal transduction pathway involved in DNA damage and cell death has not
      been previously examined in hypoxic injury in any tissue. In the present study,
      we have demonstrated that chemical hypoxia with a combination of antimycin A, a
      mitochondrial respiration inhibitor, and substrate deprivation resulted in rapid
      increase in protein tyrosine kinases activity and protein tyrosine
      phosphorylation prior to any evidence of cell death in LLC-PK1 cells. The
      inhibitors of protein tyrosine kinases, genistein, lavendustin A, tyrphostin, and
      herbimycin A provided a marked protection against chemical hypoxia-induced DNA
      damage (as measured by alkaline unwinding assay) and cell death (as measured by
      trypan blue exclusion assay). In a separate study, we confirmed the ability of
      the inhibitors, lavendustin A and herbimycin A to prevent chemical hypoxia
      induced increase in protein tyrosine kinases activity and protein tyrosine
      phosphorylation. In addition, the inhibitors used did not affect ATP depletion
      induced by antimycin A, suggesting that the inhibitors do not alter cellular
      uptake of antimycin A. Taken together, our data provide a strong evidence that
      tyrosine phosphorylation plays as important role in DNA damage and cell death in
      chemical hypoxic injury to renal tubular epithelial cells.

PMID- 9186863
TI  - Differential regulation of chemokines by leukemia inhibitory factor, interleukin
      6 and oncostatin M.
AB  - M. Leukemia inhibitory factor (LIF). oncostatin M (OsM) and interleukin-6 (IL-6)
      are members of a cytokine family, which are produced by activated macrophages and
      glomerular mesangial cells. These cytokines have been implicated in the
      pathogenesis of glomerular inflammation, but their action on glomerular cells is
      presently unclear. Therefore, we examined the effects of IL-6, OsM and LIF on
      chemokine synthesis of rat mesangial cells in culture. While LIF as well as IL-6
      up-regulated monocyte chemotactic protein-1 (MCP-1) mRNA expression, OsM showed
      no such effect. The induction of MCP-1 mRNA by LIF and IL-6 was transient,
      peaking at one to two hours and two to three hours, respectively, and returning
      to background levels within several hours. Induction of MCP-1 mRNA by LIF and IL
      6 was strongly inhibited by dexamethasone. LIF activated STAT factors in
      mesangial cells, suggesting their involvement in signal transduction pathways
      that lead to LIF-stimulated up-regulation of MCP-1 mRNA. By contrast, LIF. IL-6
      and OsM failed to affect the expression of the chemokines, macrophage
      inflammatory protein-2 (MIP-2) and RANTES. The rapid, transient and differential
      regulation of MCP-1 expression induced by LIF and IL-6 contrasted with uniformly
      powerful effects of the proinflammatory cytokines IL-1 beta and TNF alpha that
      induced all tested chemokines for prolonged time periods. These results suggest
      that the selective and transient induction of MCP-1 by LIF and IL-6 may play a
      role in the preferential attraction of monocytes to the injured glomerulus.

PMID- 9186864
TI  - Acquired VLDL receptor deficiency in experimental nephrosis.
AB  - Nephrotic syndrome (NS) is commonly associated with elevation of plasma very low
      density lipoprotein (VLDL) and triglyceride concentrations. VLDL receptor (VLDL
      R) is a novel protein that specifically binds and internalizes VLDL particles and
      is primarily distributed in heart, skeletal muscle, brain and adipose tissue.
      Based on these properties, VLDL-R is thought to play a role in VLDL and
      triglyceride metabolism. The present study was undertaken to test the hypothesis
      that elevation of plasma VLDL in NS may be, in part, related to VLDL-R
      deficiency. To this end, heart and skeletal muscle VLDL-R protein (Western blot)
      and mRNA (Northern blot) were measured at various points in the course of
      puromycin-induced NS in rats. The results were compared with those obtained in
      the placebo-treated normal control animals. The NS group showed a significant
      decline in VLDL-R protein (relative to total plasma membrane protein mass) in the
      heart and skeletal muscle paralleling the rise in plasma VLDL and triglyceride
      concentrations. The fall in VLDL-R protein was accompanied by a parallel decline
      in VLDL-R mRNA in the heart but not skeletal muscle. VLDL-R protein was directly
      related to proteinuria and inversely related to plasma VLDL and triglyceride
      concentrations. In conclusion, puromycin-induced NS in rats is associated with
      profound reduction in heart and skeletal muscle VLDL receptor protein. Acquired
      VLDL-R deficiency, shown for the first time here, may contribute to elevation of
      plasma concentration of triglyceride-rich VLDL in the nephrotic rat. Recognition
      of this abnormality reveals another dimension of the complex dysregulation of
      lipid metabolism in NS. The precise mechanism responsible for NS-induced VLDL-R
      deficiency in this model is not clear and awaits further investigation.

PMID- 9186865
TI  - Osteopontin regulation in cultured rat renal epithelial cells.
AB  - Osteopontin is a secreted, arginine-glycine-aspartate (RGD)-containing
      phosphoprotein that is up-regulated in kidney cortical tubular epithelial cells
      in many experimental models of tubulointerstitial fibrosis. Its close association
      with infiltrating macrophage in this disease and its ability to directly
      stimulate macrophage migration has made it a key target as a molecule likely to
      be important in mediating renal inflammation. The mechanism responsible for
      osteopontin up-regulation in kidney disease is unknown, but may involve induction
      by specific cytokines released by damaged glomeruli or other parts of the kidney,
      prior to the onset of interstitial disease. We have investigated this hypothesis
      by testing the effects of angiotensin II, bFGF, TGF beta 1, EGF, and IGF,
      important renal cytokines, on osteopontin regulation in cultured NRK52E cells, a
      rat renal epithelial cell line. Using Northern blot, Western blot, and ELISA
      analyses, we find that NRK52E cells constitutively express low levels of
      osteopontin mRNA and protein. TGF beta 1 and EGF are potent inducers of
      osteopontin mRNA and protein in those cells. mRNA stability and nuclear run on
      assays suggest that induction of osteopontin expression by TGF beta 1 and EGF is
      via increased transcription of the osteopontin gene. In contrast, IGF-1,
      angiotensin II, and PDGF BB did not significantly modulate osteopontin expression
      in NRK52E cells. These studies are consistent with the hypothesis that release of
      potent cytokines by the injured kidney might be one mechanism whereby elevated
      levels of osteopontin are synthesized by cortical tubular epithelial cells early
      in tubulointerstitial disease.

PMID- 9186866
TI  - Distribution of heparin-binding EGF-like growth factor protein and mRNA in the
      normal rat kidneys.
AB  - Heparin-binding EGF-like growth factor (HB-EGF), a newly discovered potent
      mitogen and chemoattractant for smooth muscle cells, is a member of the EGF
      superfamily and binds to EGF receptors. To investigate the role of HB-EGF in the
      kidney, we determined the distribution of HB-EGF immunohistochemically in normal
      rat kidneys. The localization of mRNA expression was also studied by in situ
      hybridization, using a synthesized digoxigenin-labeled anti-sense riboprobe of HB
      EGF. Immunohistochemical and in situ hybridization studies revealed that the
      tubular epithelial cells of the S3 segment of the outer stripe in the outer
      medulla were the predominant renal source of HB-EGF. In addition, in the
      immunohistochemical analysis, HB-EGF was ubiquitously present in the epithelial
      cells of the proximal tubules and the arterial smooth muscle cells, while HB-EGF
      expression was not detected in other parts of the kidney, including the
      glomeruli. Although EGF receptors were found to be present in the proximal
      tubules as well as in the distal tubules and collecting ducts, EGF has not been
      found to be expressed in the proximal tubules. Therefore, the present results
      indicate that HB-EGF might be a ligand for EGF receptors in the proximal tubules
      and might play a role in the functions of proximal tubules.

PMID- 9186867
TI  - Activation of renin synthesis is dependent on intact nitric oxide production.
AB  - The present study investigated whether or not nitric oxide (NO) synthesis
      mediates mechanisms regulating activation of renin formation. Studies were
      performed on afferent arterioles freshly isolated from the rat kidney. We have
      shown previously that this preparation is a useful model to study regulation of
      renin synthesis and secretion. The expression of renin mRNA was assessed by
      ribonuclease protection assay, and total renin content and renin secretion by
      radioimmunoassay. In afferent arterioles isolated from rats treated with the
      angiotensin-converting enzyme inhibitor ramipril, renin mRNA levels, total renin
      content and renin secretion were increased threefold compared to untreated
      controls. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME)
      in the ramipril-treated rats, abolished the increase in renin mRNA levels, total
      renin content and renin secretion. In other animals furosemide, a diuretic acting
      on macula densa cells, activated renin synthesis to a level similar to that found
      in the ramipril-treated group. Addition of L-NAME to the furosemide-treated rats
      suppressed the increases in renin mRNA levels, total renin content and renin
      secretion, suggesting that NO acts on renin activation by a mechanism independent
      of angiotensin II. In separate experiments, the inhibitory effect of L-NAME on
      the activation of renin secretion was abolished when afferent arterioles were
      treated with nicardipine, an L-type Ca2+ channel blocker, suggesting that the
      suppression of renin activation during NO inhibition is due to increased Ca2+
      entry. Since endothelin is a potent mediator of Ca2+ influx and an inhibitor of
      renin release, we tested whether or not endothelin could be involved in the
      inhibitory effect of L-NAME on renin secretion. Application of the endothelin
      receptor antagonist, bosentan, in vitro mimicked the effect of nicardipine. In
      addition, bosentan coadministered with L-NAME in vivo blunted the inhibitory
      effect of L-NAME and restored the increases in renin mRNA level, synthesis and
      secretion. These data indicate that the physiological mechanism(s) regulating
      activation of renin synthesis and secretion are impaired during NO inhibition,
      probably because of increased Ca2+ influx. This increase in calcium flux is
      mediated at least partially by the action of endothelin.

PMID- 9186868
TI  - Extrahepatic C6 is as effective as hepatic C6 in the generation of renal C5b-9
      complexes.
AB  - In order to study the contribution of extrahepatic C6 to anti-Thy1.1 nephritis,
      C6 deficient PVG/c- livers were grafted in C6 sufficient PVG/c+ rats (Tx-L).
      Infusion of anti-Thy1.1 antibodies in Tx-L and PVG/c+ rats resulted in generation
      of C5b-9 complexes and subsequent glomerular injury, while infusion of anti
      Thy1.1 antibodies in PVG/c- rats revealed no detectable C6 deposition. Because C6
      mRNA was expressed in both liver and kidney tissue of PVG/c+ rats, we assessed
      whether production of C6 in the kidney alone was sufficient for glomerular
      injury. One kidney of a PVG/c- rat was replaced with a PVG/c+ kidney (Tx + K)
      followed by administration of anti-Thy1.1 antibodies. C6 deposits were detectable
      neither in PVG/c+ kidneys nor in PVG/c- kidneys of Tx + K rats, indicating that
      C6 production in PVG/c+ kidneys alone is not sufficient to contribute to renal
      injury. That C6 production had occurred was suggested by the presence of equal
      amounts C6 mRNA in control PVG/c+ kidneys and in grafted PVG/c+ kidneys of Tx + K
      rats. C6 mRNA expression in kidney tissue of PVG/c+ rats is presumably derived
      from peritubular sites. In conclusion, we have demonstrated that extrahepatic,
      but not renal synthesis of, C6 is sufficient to contribute to glomerular injury
      during anti-Thy1.1 nephritis.

PMID- 9186869
TI  - Mesangial cell actin disassembly in high glucose mediated by protein kinase C and
      the polyol pathway.
AB  - High glucose alters mesangial cell cytoskeletal structure and function. We
      postulated that high glucose causes mesangial cell filamentous (F) actin
      disassembly through a protein kinase C (PKC) mechanism involving the polyol
      pathway. Rat mesangial cells (passage < 10, N = 60/group) were growth-arrested
      and then cultured in glucose 5.6 mM (NG), 15 mM (MG) or 30 mM (HG) for 48 hours,
      with or without the aldose reductase inhibitor Tolrestat 0.3 mM. F and globular
      (G) actin were labeled with rhodamine-phalloidin and FTTC-DNase-1, respectively.
      Both fluorescence probes were imaged simultaneously in each cell using dual
      channel confocal laser microscopy. In HG, F-actin disassembly was observed and
      measured by a 40% decrease in F-/G-actin fluorescence intensity ratio (no change
      in NG + mannitol 24.4 mM). In separate experiments, cells were labeled with
      BODIPY FL-bisindolylmaleimide, specific for most PKC isoforms, and fluorescence
      intensity/cell was measured. In NG, exposure to phorbol 12-myristate 13-acetate
      (PMA) 0.1 microM for 15 minutes caused perinuclear and nuclear translocation of
      PKC, and F-actin disassembly identical to observations in HG alone. In HG, total
      PKC fluorescence increased by 50% and PMA exposure for 24 hours normalized both
      the total PKC and F-/G-actin fluorescence ratio. In NG and HG, exposure (15 min)
      to PMA 0.1 microM increased PKC activity three to four times, measured by in situ
      32P-phosphorylation of EGF-receptor substrate. By immunofluorescence and confocal
      imaging, diacylglycerol-sensitive PKC-delta was localized to the cytosol in NG,
      and after 15 minutes exposure to PMA, translocated to the perinuclear region and
      plasma membrane. In HG. PKC-delta immunofluorescence was significantly
      increased/cell, distributed in a cytoskeletal pattern and the intensity was
      glucose-concentration dependent (30 > 15 > 5.6 mM). In HG, exposure to PMA for 24
      hours returned the PKC-delta fluorescence to the intensity and cytosolic pattern
      observed in NG, and simultaneously prevented F-actin disassembly. Tolrestat
      significantly reduced the total PKC and PKC-delta fluorescence intensity and F
      actin disassembly observed in HG. Immunoblot confirmed increased PKC-delta in HG,
      which was normalized by Tolrestat. The immunofluorescence pattern of
      diacylglycerol-insensitive PKC-delta was unchanged in HG, with PMA or Tolrestat.
      We conclude that mesangial cell F-actin disassembly in high glucose is likely
      mediated through diacylglycerol-sensitive PKC isoforms, including PKC-delta and
      involves the polyol pathway.

PMID- 9186870
TI  - Effect of interleukin-10 treatment on crescentic glomerulonephritis in rats.
AB  - This study examined the utility of interleukin-10 (IL-10), a cytokine with potent
      anti-macrophage and anti-Th1 activity, in the treatment of experimental anti
      glomerular basement membrane (GBM) nephritis in the rat. Accelerated anti-GBM
      disease was induced in Sprague-Dawley rats by immunization with rabbit IgG,
      followed five days later by an i.v. injection of anti-GBM serum. Groups of four
      rats received daily s.c. injections of recombinant mouse IL-10 (500, 10 or 0.2
      microgram/kg/day) or saline (control) from the time of anti-GBM serum
      administration until being killed on day 14. IL-10 treatment suppressed the skin
      DTH response as measured by skin thickness (44 to 62% decrease vs. control, p <
      0.05). Compared to saline controls, IL-10 treatment had no beneficial effect on
      renal function, proteinuria or histological damage (including crescent formation)
      at any dose examined. A detailed analysis of high dose IL-10 (500
      micrograms/kg/day) and saline treated animals was undertaken. Saline controls had
      marked glomerular macrophage accumulation and proliferation, which was augmented
      by IL-10 treatment (46 to 99% increases and 44 to 143% increases, respectively; p
      < 0.05). Immunohistochemical staining found no difference in the state of
      macrophage activation between the groups, as determined by the percentage of
      macrophages expressing IL-1 beta protein. Northern blot analysis of whole kidney
      RNA demonstrated an 830% increase in IL-1 beta mRNA expression in saline controls
      compared to normal rat kidney. High dose IL-10 treatment reduced IL-1 beta mRNA
      levels by 60% compared to controls (P < 0.05), but did not significantly reduce
      glomerular IL-1 beta protein expression. IL-10 treatment increased serum levels
      of rat anti-rabbit IgG, induced a rat anti-mouse IL-10 response and augmented
      glomerular deposition of rat C3. In conclusion, IL-10 was not an effective
      treatment for rat crescentic anti-GBM glomerulonephritis. This may have been due
      to the failure of IL-10 to achieve a sufficient reduction in IL-1 beta expression
      and macrophage participation in disease, or promotion of the Th2 immune response.

PMID- 9186871
TI  - Cholesterol feeding accentuates the cyclosporine-induced elevation of renal
      plasminogen activator inhibitor type 1.
AB  - Long-term cyclosporine (CsA) therapy is accompanied by the occurrence of
      hypercholesterolemia and renal interstitial fibrosis. The present study
      investigates the effect of dietary cholesterol on CsA-induced lipid disturbances
      in the rat and on CsA nephrotoxicity. Since plasminogen activator inhibitor type
      1 (PAI-1) is a major inhibitor of matrix degradation and elevated plasma PAI-1
      levels are reported to be associated with increased low-density lipoprotein (LDL)
      cholesterol, PAI-1 was examined in the kidneys of rats fed a sodium-deficient
      diet, with or without cholesterol. After nine weeks, both diet groups were
      subdivided into a CsA-treated group and a vehicle-treated group. Although
      cholesterol feeding significantly aggravated CsA-induced renal function
      impairment, CsA-induced histological lesions were comparable in both diet groups.
      Cholesterol feeding significantly decreased high-density lipoprotein (HDL)
      cholesterol irrespective of the treatment, while CsA treatment significantly
      elevated serum triglycerides irrespective of the diet. Cholesterol feeding alone
      did not increase the number of infiltrating cells in the renal interstitium. In
      contrast, in both diet groups CsA treatment caused a significant influx of
      macrophages, while combined treatment with CsA and cholesterol additionally
      elevated the number of T-helper cells in the cortex. In all rats, PAI-1
      immunostaining was found mainly in intracellular vesicles (lysosomes) in proximal
      tubules, which stained most intensely in fibrotic areas of kidneys from CsA
      treated rats. Cholesterol feeding enhanced the CsA-induced elevation of renal PAI
      1 immunostaining to a significant level. These results show that, although serum
      creatinine, PAI-1 staining and T cell influx were significantly increased in the
      cholesterol-fed CsA-treated group compared to the other groups, renal CsA-induced
      histological lesions were not influenced by cholesterol feeding after short-term
      (3 weeks) CsA administration. To what extent the more pronounced proximal tubular
      PAI-1 (inhibitor of matrix degradation) immunostaining in fibrotic areas in the
      cortex of cholesterol-fed CsA-treated rats contributes to the progression of CsA
      induced renal fibrosis remains to be determined.

PMID- 9186872
TI  - Intrarenal distribution of rabbit PKC zeta.
AB  - To elucidate roles of protein kinase C (PKC) zeta in rabbit kidney, PKC zeta was
      cloned from a rabbit kidney cortex cDNA library. Sequencing revealed a 2113 m
      insert with an open reading frame encoding a protein of 591 amino acids. The
      predicted amino acid sequence is 93.7% identical with rat PKC zeta. In situ
      hybridization in rabbit kidney with a riboprobe generated from the cloned cDNA,
      showed PKC zeta mRNA is highly expressed in proximal tubule, thick limb, and
      collecting duct. No message was detected over glomerular cells.
      Immunohistochemical studies using a monoclonal antibody against PKC zeta
      confirmed this distribution with low expression in vascular elements and high
      expression in tubule epithelium. Confocal microscopy showed diffuse cytosolic
      immunoreactivity in confluent cultured cortical collecting ducts (CCDs). However,
      in subconfluent cells, immunoreactivity was restricted to the peri-nuclear area.
      This differential distribution of PKC zeta in the CCD suggests that PKC zeta
      action be involved in growth and differentiation of the collecting duct. In
      conclusion, PKC zeta is differentially expressed in the rabbit kidney with high
      expression in the tubule epithelium and little expression in vascular elements.
      These studies suggest an important role for PKC zeta along the nephron.

PMID- 9186873
TI  - Anti-angiogenic compound (TNP-470) inhibits mesangial cell proliferation in vitro
      and in vivo.
AB  - Growth factors, especially basic fibroblast growth factor (bFGF), platelet
      derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) are
      known to play key roles in the pathogenesis of mesangial proliferative
      glomerulonephritis. TNP-470 (AGM-1470), a potent anti-angiogenic compound, has
      anti-growth factor properties and inhibits the activation of cyclin-dependent
      kinase (cdk) 2 and phosphorylation of RB protein. We investigated whether TNP-470
      could suppress growth factor induced mesangial cell proliferation in vitro and
      experimental model of mesangial proliferative glomerulonephritis in vivo. TNP-470
      inhibited potently PDGF- and bFGF-stimulated proliferation of rat mesangial cells
      in vitro (IC50 = 50 pg/ml). In anti-Thy 1.1 glomerulonephritis, high dose use of
      TNP-470 (20 mg/kg/day) markedly suppressed mesangial cell proliferation and
      mesangial matrix expansion on day 6; however, mesangiolysis remained. Low dose
      use of TNP-470 (10 mg/kg/day) moderately inhibited mesangial cell proliferation
      and mesangial matrix synthesis, and induced appropriate glomerular healing on day
      14 in anti-Thy 1.1 glomerulonephritis. Thus, TNP-470 potently inhibits growth
      factor-induced proliferation of mesangial cells in vitro, and mesangial cell
      proliferation and extracellular matrix expansion in anti-Thy 1.1
      glomerulonephritis in vivo. These results suggest a novel therapeutic potential
      of TNP-470 in mesangial proliferative glomerulonephritis.

PMID- 9186874
TI  - Effects of partial nephrectomy on the expression of osmolyte transporters.
AB  - Na+/myo-inositol cotransporter (SMIT) and Na+/Cl-/betaine-gamma-amino-n-butyric
      acid transporter (BGT-1) are the major osmolyte transporters that are regulated
      by extracellular osmolarity. We have recently shown localization and rapid
      regulation of the mRNAs for these transporters in rat kidney. In the present
      study, we examined the expression of SMIT and BGT-1 in partial nephrectomized
      rats in order to assess the change in local osmolarity following reduction of
      renal mass. Four weeks after 5/6 nephrectomy (NX), the rats were compared to sham
      operated control animals (CONT). Northern analysis using RNA of whole kidney
      indicated that there were little differences in the levels of SMIT and BGT-1
      mRNAs between the two groups. In situ hybridization revealed that signals for
      both transporter mRNAs were markedly reduced in the inner medulla of the remnant
      kidney. In contrast, these signals in the outer medulla increased following
      nephrectomy. SMIT signals in the cortex increased as well. Grain density,
      determined by counting grain number per cell, revealed that the signals in the
      inner medullary collecting ducts were markedly reduced whereas those in the thick
      ascending limbs of Henle (TAL) as well as macula densa cells were significantly
      increased. The signals in the TAL and macula densa were reduced by furosemide
      administration. The increased expression in NX rats may reflect the increased
      NaCl transport and high local osmolarity in this segment.

PMID- 9186875
TI  - Pyelonephritis provokes growth retardation and apoptosis in infant rat renal
      cortex.
AB  - Childhood pyelonephritis is a common cause of renal cortical scarring and
      hypoplastic kidneys. To understand the mechanisms underlying the cortical
      lesions, urinary tract infection was induced in three-week-old rats by an
      intravesical infusion of E. coli, type 06 K13 HL a rat nephropathogenic strain.
      Four days after infection, histopathological examination showed marked
      infiltration of leukocytes in the medullary tissue adjoining the calyces and
      pelvis. In the cortex, signs of inflammation were found only in the cortical zone
      adjacent to the pelvis. No cells indicative of inflammation were observed in
      other parts of the cortex. Immunohistochemistry for endogenous proliferating cell
      nuclear antigen (PCNA) demonstrated a marked decrease in immunoreactivity in
      proximal tubular (PT) cells. The mitotic response of PT cells, assessed by 3H
      thymidine autoradiography, showed a highly significant decrease during the first
      four days after induction of the infection. Four days after infection, a
      transient increase in apoptotic cells was observed in cortical cells outside the
      inflammatory areas. No increase in apoptotic cells was detected in the cortex 10
      days after infection. Only a few apoptotic cells were detected in the control
      kidneys. In conclusion, the data indicate that inhibition of cell proliferation
      and enhancement of apoptosis may contribute to the renal parenchymal loss after
      childhood pyelonephritis.

PMID- 9186876
TI  - Influence of nycthemeral blood pressure pattern in treated hypertensive patients
      on hemodialysis.
AB  - Arterial hypertension in end-stage renal disease (ESRD) patients is characterized
      by an altered nycthemeral blood pressure (BP) rhythm and an increased pulse
      pressure, and it could be suggested that this association of risk factors plays a
      major role in the cardiovascular prognosis of this population. The aim of this
      study was to determine the influence of nycthemeral BP pattern on arterial
      distensibility and pulsatile components of BP in treated hypertensive patients on
      regular hemodialysis. Forty-two hypertensive patients were included, and all
      underwent ambulatory BP and pulse wave velocity (PWV) measurements between the
      femoral and carotid arteries. The patients were divided into two groups according
      to the magnitude of the nocturnal fall in BP: dippers and non-dippers. The groups
      were similar in gender, age, duration of hemodialysis, body mass index, body
      size, history of cardiovascular complications, class and number of
      antihypertensive drugs used per patient. PWV was significantly higher in non
      dippers. For the whole population, a stepwise regression analysis showed that PWV
      and erythropoietin therapy were independently related to the impaired nycthemeral
      BP pattern. In addition to its pressor effect, erythropoietin could have a
      deleterious influence on the ambulatory BP profile of treated hypertensive
      patients in ESRD. Arterial distensibility and nycthemeral BP impairment are
      linked, and these cardiovascular risk factors should be taken into account
      together for the management of hypertensive hemodialysis patients.

PMID- 9186877
TI  - Ritodrine- and terbutaline-induced hypokalemia in preterm labor: mechanisms and
      consequences.
AB  - The effects of ritodrine and terbutaline on potassium homeostasis, renal
      function, and cardiac rhythm were assessed in women treated with these drugs for
      preterm labor. Timed blood and urine samples were obtained for two hours before
      and during six hours of intravenous ritodrine (N = 5) and terbutaline (N = 5)
      administered in pharmacologically equivalent doses. No differences were found in
      any parameters affecting potassium homeostasis or renal function between these
      drugs. A decrease in mean plasma potassium of 0.9 mEq/liter occurred after 30
      minutes of drug infusion (4.2 +/- 0.1 to 3.3 +/- 0.1 mEq/liter, P < 0.005) before
      any significant changes in plasma glucose (75.0 +/- 4.7 to 93.7 +/- 6.1 mg/dl, P
      = NS) or plasma insulin (12.4 +/- 6.0 to 28.4 +/- 5.1 mU/ml, P = NS). The mean
      plasma potassium after four hours of drug infusion was 2.5 +/- 0.1 mEq/liter.
      Plasma insulin rose to a level known to induce cellular potassium uptake (39.2 +/
      7.7 mU/ml) after 60 minutes of drug therapy and remained at this level for four
      hours. Hyperlactatemia occurred at four hours (4.7 +/- 0.8 mmol/liter) and the
      plasma lactate/pyruvate ratio increased in a 10:1 ratio. Both drugs significantly
      reduced glomerular filtration rate, sodium, potassium, and chloride excretion and
      urinary flow rate. Changes in acid-base homeostasis, plasma aldosterone, or renal
      potassium excretion did not contribute to ritodrine-or terbutaline-induced
      hypokalemia. In 83 women with preterm labor randomly assigned to ritodrine (N =
      42) or terbutaline (N = 41), the maximum decrease in plasma potassium occurred
      after six hours of drug infusion. During Holter monitoring, 3 of 14 women treated
      with ritodrine or terbutaline developed symptomatic cardiac arrhythmias at the
      lowest plasma potassium while no women treated with saline and morphine (N = 12)
      developed cardiac arrhythmias (P = 0.14). We conclude that ritodrine and
      terbutaline induce profound hypokalemia by stimulating cellular potassium uptake
      and both drugs cause significant renal sodium and fluid retention and cardiac
      arrhythmias. Careful monitoring of electrolytes, fluid balance, and cardiac
      rhythm should occur during tocolytic therapy with ritodrine or terbutaline.

PMID- 9186878
TI  - Predominant Th1 cell infiltration in acute rejection episodes of human kidney
      grafts.
AB  - T-cells and their cytokines are thought to play a major role in the genesis of
      cellular infiltration and rejection in human kidney allografts. Production of Th1
      (IFN-gamma) and Th2-type (IL-4 and IL-5) cytokines was assessed in a large series
      of T-cell clones, derived from core biopsies of kidney grafts in 10 patients with
      acute interstitial grade I/II rejection (AIR), 6 patients with a histology of
      "borderline rejection" (BLR) and 3 with cyclosporine A (CsA) toxicity, all
      receiving standard maintenance immunosuppression. Biopsies were pre-cultured in
      IL-2 in order to preferentially expand T-cells activated in vivo, and T-cell
      blasts were cloned with phytohemagglutinin (PHA) and IL-2 using a highly
      efficient (23 to 98%) cloning technique. A total of 483 T-cell clones obtained
      from AIR episodes were compared with 346 and 132 clones derived from patients
      with BLR episodes and CsA toxicity, respectively. In two series of 22 AIR and 77
      BLR T-cell clones, alloreactivity against donor cells was shown by 25 and 14% of
      CD8+ and 21 and 4% of CD4+ clones, respectively. When stimulated by donor-derived
      EBV B-cells, all these alloreactive clones produced IFN-gamma, but not IL-4 or IL
      5 (Th1 clones). Upon stimulation with PHA, the principal qualitative and
      quantitative differences between AIR- and BLR-derived T-cell clones were that
      cells derived from AIR patients: (i) showed significantly higher proportions (80
      +/- 15 vs. 55 +/- 13%) of Th1 clones in their progeny; (ii) included smaller
      proportions (3 +/- 4 vs. 20 +/- 17%) of clones incapable of producing IFN-gamma,
      IL-4 or IL-5 ('null' clones); and (iii) produced significantly higher quantities
      of IFN-gamma (100 +/- 50 vs. 36 +/- 7 U/10(6) cells/ml), these quantities also
      being significantly correlated (r = 0.83) with the degree of interstitial graft
      infiltration (item 'i' in the Banff histological grading). The clones derived
      from CsA toxicity biopsies exhibited a pattern very similar to that found in BIR
      cases. These data lead us to conclude that the powerful inflammatory response
      elicited in acute rejection of a kidney graft recruits and activates both
      allospecific and non-specific Th1 effector cells, which are primed to high IFN
      gamma production. Our results also suggest that IFN-gamma could contribute, at
      least in part, to the degree of graft infiltration and to the severity of the
      rejection episode.

PMID- 9186879
TI  - The nitric oxide donor nitroprusside intraperitoneally affects peritoneal
      permeability in CAPD.
AB  - Nitroprusside is a nitric oxide (NO) donor. To investigate effects of
      nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal
      permeability analyses were performed. Ten stable CAPD patients were studied twice
      within one week with glucose based dialysate (1.36% Dianeal) with and without
      addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of
      CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable
      metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in
      plasma and dialysate. The MTACs of low molecular weight solutes were greater with
      nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP)
      versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP)
      versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective
      peritoneal surface area with nitroprusside. Furthermore, the restriction
      coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23
      (NP) (P = 0.02), suggesting some effect also on the size selectivity to these
      solutes. The effect of nitroprusside on the clearances of serum proteins was more
      pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70%
      for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in
      size selectivity was reflected in a decrease in the restriction coefficient for
      macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in
      the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using
      computer simulations, was done to analyze these effects in terms of the pore
      theory, using a convection model and a diffusion model for the transport of
      macromolecules. Nitroprusside led to an increase of both the large pore radius
      and the small pore radius and of the unrestricted area over diffusion distance.
      These effects were more pronounced with the diffusion model. The MTAC CO2 was not
      different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than
      expected on the basis of the molecular weight during both dwells. The
      dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside:
      0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With
      nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its
      molecular weight (P < 0.001). This points to local generation of cGMP after the
      addition of nitroprusside, induced by NO. No differences were found in the
      dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha
      and thromboxane B2 after addition of nitroprusside. The transcapillary
      ultrafiltration rate and the net ultrafiltration rate during four hours were not
      different with nitroprusside. In conclusion, nitroprusside i.p. increased the
      effective peritoneal surface area and the intrinsic permeability, but the
      peritoneal blood flow did not change. The greater than expected D/P ratios of
      cGMP point to local generation of cGMP with nitroprusside, induced by NO.

PMID- 9186880
TI  - Genomic organization of a human cystine transporter gene (SLC3A1) and
      identification of novel mutations causing cystinuria.
AB  - Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine
      nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter
      (SLC3A1) have been identified in patients with cystinuria establishing one
      molecular cause for the disease. To facilitate systematic screening of this gene
      for mutations, we have delineated the complete genomic organization of the SLC3A1
      coding region using polymerase chain reaction strategies. The complete coding
      region of the gene is contained within a single yeast artificial chromosome clone
      and consists of 10 exons and 9 introns. Oligonucleotide primers capable of
      amplifying selected exons have been made and used in mutational analysis of DNA
      from 24 cystinuria probands. We illustrate the usefulness of this approach by
      identifying two novel SLC3A1 mutations. One novel mutation causes replacement of
      a highly conserved arginine residue (arginine-452) with tryptophan in the
      cytoplasmic loop between the putative third and fourth membrane spanning
      segments. A second previously unreported mutation results in replacement of a
      highly conserved tyrosine (tyrosine-461) residue with histidine in the same
      region of the protein. In addition, we detected three previously reported SLC3A1
      mutations, R270X, 1500 +1/G to T, and M467T, the latter being present in
      approximately 20% of cystinuria chromosomes examined. Our findings provide a
      foundation for the development of more accessible diagnostic screening assays for
      detecting SLC3A1 mutations using patient genomic DNA, and also contribute to the
      emerging spectrum of cystinuria genotypes.

PMID- 9186881
TI  - Role of alpha v integrins in mesangial cell adhesion to vitronectin and von
      Willebrand factor.
AB  - This study demonstrates (by flow cytometry and immunoprecipitation after cell
      surface radiolabeling and by using monoclonal antibodies to alpha v, beta 3, and
      alpha v beta 3 and alpha v beta 5 complexes) that alpha v beta 3, the vitronectin
      receptor, and alpha v beta 5 are expressed in vitro on cultured human mesangial
      cells (HMC) of the 5th to 8th passages. Antibodies to alpha v, beta 3 and alpha v
      beta 3 respectively precipitated an alpha beta heterodimer with molecular weights
      of 140 and 97 kDa. We analyzed the role of the various integrins in HMC
      interactions with vitronectin, and with fibronectin and von Willebrand factor
      (vWf), which are synthetized respectively by mesangial and endothelial cells.
      Cell adhesion increased in a dose dependent manner with the concentration of
      plastic-coated matrix protein and vWf. Inhibition of cell attachment with
      monoclonal antibodies to integrins indicated that HMC adhesion to vWf primarily
      involves alpha v beta 3, and that alpha v beta 5 may also contribute to cell
      binding to vWf. Adhesion to vitronectin involves both alpha v beta 3 and alpha v
      beta 5 complexes. In contrast, adhesion to fibronectin was not affected by
      monoclonal antibodies to alpha v beta 3 and alpha v beta 5 complexes. We propose
      that integrins alpha v beta 3 and alpha v beta 5, present on HMC, could mediate
      an interaction between mesangial and endothelial cells by binding to vWf,
      released at the basal site of endothelial cells.

PMID- 9186882
TI  - Predictors of the progression of renal disease in the Modification of Diet in
      Renal Disease Study.
AB  - The Modification of Diet in Renal Disease (MDRD) Study examined the effects of
      dietary protein restriction and strict blood pressure control on the decline in
      glomerular filtration rate (GFR) in 840 patients with diverse renal diseases. We
      describe a systematic analysis to determine baseline factors that predict the
      decline in GFR, or which alter the efficacy of the diet or blood pressure
      interventions. Univariate analysis identified 18 of 41 investigated baseline
      factors as significant (P < 0.05) predictors of GFR decline. In multivariate
      analysis, six factors--greater urine protein excretion, diagnosis of polycystic
      kidney disease (PKD), lower serum transferrin, higher mean arterial pressure,
      black race, and lower serum HDL cholesterol--independently predicted a faster
      decline in GFR. Together with the study interventions, these six factors
      accounted for 34.5% and 33.9% of the variance between patients in GFR slopes in
      Studies A and B, respectively, with proteinuria and PKD playing the predominant
      role. The mean rate of GFR decline was not significantly related to baseline GFR,
      suggesting an approximately linear mean GFR decline as renal disease progresses.
      The 41 baseline predictors were also assessed for their interactions with the
      diet and blood pressure interventions. A greater benefit of the low blood
      pressure intervention was found in patients with higher baseline urine protein.
      None of the 41 baseline factors were shown to predict a greater or lesser effect
      of dietary protein restriction.

PMID- 9186883
TI  - Intrarenal hemodynamic abnormalities in diabetic nephropathy measured by duplex
      Doppler sonography.
AB  - Intrarenal hemodynamics were studied by duplex Doppler sonography in 112
      inpatients with type II diabetes mellitus (DM; 65 males, 47 females, 58 +/- 13
      years old). The resistive index (RI) and pulsatility index (PI) of the interlobar
      arteries were calculated. The patients were divided into four groups: group I
      consisted of patients with urinary albumin excretion (UAE) < 20 micrograms/min (N
      = 42), group II with 20 < or = UAE < 200 (N = 28), group III with UAE > or = 200
      (N = 25), and group IV with serum creatinine > or = 1.5 mg/dl (N = 17). Both RI
      and PI values in groups II, III, and IV were significantly higher than those in
      the controls (age- and sex-matched healthy persons, N = 37; P < 0.001), and those
      in group IV were significantly higher than those in groups I, II, and III (P <
      0.0001). Multiple regression analysis revealed that RI values in DM patients were
      significantly affected by creatinine clearance, age, and duration of diabetes (R2
      = 0.554, P < 0.0001). When intima-medial thickness (IMT) of the femoral and
      carotid arteries were measured by B-mode ultrasonography, RI values were
      significantly correlated with both the femoral and carotid arterial IMT. These
      results demonstrate that intrarenal hemodynamic abnormalities are present in type
      II DM patients with nephropathy, and that intrarenal hemodynamics are affected by
      decreased glomerular function and also probably by advanced arteriosclerosis.

PMID- 9186884
TI  - Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a
      prospective post-mortem study.
AB  - The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was
      evaluated in a prospective study of joint samples obtained at autopsy in 54
      patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80
      (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological
      signs of A beta 2m were present in 2 and 4% of them, respectively. A control
      group of 34 patients without end-stage renal disease, autopsied during the same
      period was used as a reference. The 153 sampled joints (1 to 8, median 2 per
      patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N =
      28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical
      birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54
      (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100%
      within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than
      13 years HD. The calculated sensitivity of the various joints for A beta 2m
      detection is significantly higher (P < 0.03) for sternoclavicular joints (97%)
      and knees (91%) than for shoulders (57%). Multivariate stepwise logistic
      regression with discriminant analysis identified both HD duration (P = 0.0008)
      and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or
      gender (P = 0.25) as independent risk factors for A beta 2m. The probability of
      joint A beta 2m was quantitated as a function of age and HD duration. In
      conclusion, A beta 2m may be observed in the large joints early after HD onset.
      Overall prevalence reaches 48% of the patients on HD for a median of 47 months.
      It is much higher than that reported on the basis of clinical or radiological
      evidence. The sternoclavicular and knee joints are more frequently (P < 0.03)
      involved than the shoulder. The easily accessible sternoclavicular joint
      therefore appears to be the best site for the early detection of A beta 2m. Both
      HD duration and age at HD onset, but not diabetic nephropathy, are independent
      risk factors for A beta 2m.

PMID- 9186885
TI  - Down-regulation of hepatic lipase expression in experimental nephrotic syndrome.
AB  - Hepatic lipase (HL) plays an important role in catabolism of chylomicron
      remnants, conversion of intermediate density lipoprotein (IDL) to low-density
      lipoprotein (LDL) and reverse transport of cholesterol to the liver. Several
      features of the nephrotic dyslipidemia point to the possible presence of HL
      deficiency. In an attempt to address this possibility, gene expression of HL was
      studied in rats with puromycin-induced nephrotic syndrome (NS). The results were
      compared with those obtained in a group of placebo-treated control animals. The
      NS group showed marked proteinuria, hypoalbuminemia, hypercholesterolemia,
      hypertriglyceridemia, normal creatinine clearance and normal hepatic tissue
      cholesterol concentration. HL activity of the liver tissue was reduced by
      approximately 60% in the NS group as compared to that found in the normal control
      group. The reduction of HL activity in the NS group was accompanied by a
      reduction of HL mRNA of virtually similar magnitude. HL activity of the liver
      tissue was inversely related to urinary protein excretion, serum cholesterol and
      serum triglyceride concentrations. In contrast, HL activity was directly related
      to serum albumin concentration and HL mRNA. No significant difference was
      observed in HL activity between the control group and the pre-nephrotic animals
      studied at days 1 and 5 following puromycin administration. This observation
      excludes an acute effect of puromycin as a possible cause of HL deficiency in the
      NS animals. Thus, NS in this model results in a marked down-regulation of HL
      expression which may, in part, contribute to the nephrotic dyslipidemia.

PMID- 9186886
TI  - Interleukin-1 receptor antagonist allele: is it a genetic link between Henoch
      Schonlein nephritis and IgA nephropathy?
AB  - Henoch-Schonlein purpura nephritis (HSPN) is a multi-organ systemic vasculitis,
      which shares many clinical, histological and immunological features with IgA
      nephropathy (IgAN). To address whether these two diseases have a common genetic
      background, the polymorphism of the variable number tandem repeat (VNTR) of IL-1
      receptor antagonist (IL-1ra) gene has been analyzed using PCR in patients
      diagnosed with HSPN (N = 43) and IgAN (N = 97), together with normal controls (N
      = 98) and patients with acute post-infectious glomerulonephritis (APGN), under
      the concept that IL-1 might play an important role in mediating pathogenesis of
      vasculitis and glomerulonephritis. It was found that the allele frequency and
      carriage rate of the interleukin-1 receptor antagonist allele (IL1RN*2) of the IL
      1ra gene increased significantly in HSPN patients as compared to IgAN (P < 0.01),
      APGN (P < 0.05) and normal subjects (P < 0.01). Interestingly, varied carriage
      rates of IL1RN*2 were found among various groups of IgAN patients presenting with
      different clinical manifestations. The carriage rate of IL1RN*2 was significantly
      higher in patients with recurrent gross hematuria than other groups of IgAN
      patients (P < 0.01). Furthermore, although the carriage rate of IL1RN*2 was
      higher in HSPN (46.5%) than average IgAN patients (26.8%; P < 0.01), there was no
      significant difference in the carriage rate of IL1RN*2 between HSPN and those
      IgAN patients with recurrent gross hematuria (42.8%l P > 0.05). It suggested that
      the IL1RN*2 allele might be a genetic marker shared by HSPN and a special group
      of IgAN patients with recurrent gross hematuria. Our preliminary observation
      provided a genetic evidence to support the hypothesis that HSPN and certain
      subgroup of IgAN are closely related diseases. Such an association of the gene
      polymorphism of IL-1ra between HSPN and IgAN with recurrent gross hematuria might
      serve as a key to explore their pathogenesis and eventually a specific
      intervention.

PMID- 9186887
TI  - Impact of surgery on nitric oxide in rats: evidence for activation of inducible
      nitric oxide synthase.
AB  - We investigated the effect of euvolemic surgical preparation, on chemical indices
      of activity of the nitric oxide (NO) system, in anesthetized, acutely prepared
      rats. The urinary excretion of NO2+NO3 (UNOXV) and cGMP (UcGMPV) increased
      progressively during the experiment. Pretreatment with aminoguanidine or
      dexamethasone, inhibitors of inducible NO synthase (iNOS), prevented the increase
      in UNOXV and UcGMPV but had no impact on mean arterial pressure (BP), renal
      vascular resistance (RVR) or GFR. Since these variables did not change in the
      conscious rat, the increased UNOXV results from some aspect of the acute surgical
      preparation. When acutely prepared rats received L-NAME, a non-specific NOS
      inhibitor, BP and RVR increased but paradoxical increases in UNOXV and UcGMPV
      were also seen. Nonselective NOS inhibition (+L-NAME) was fatal in 50% of acutely
      prepared rats, causing cardiac contracture. The same dose of L-NAME produced no
      deaths in either conscious chronically catheterized rats or in acutely prepared
      rats, previously subjected to sterile surgery and acute L-NAME in the conscious
      state. These data indicate that acute, nonsterile surgery induces expression of
      iNOS, but that the additional NO generated has no obvious cardiovascular/renal
      actions. Acute UNOXV and UcGMPV do not predict total NO production, or
      "hemodynamically active" NO. Generalized NO inhibition in rats acutely stressed
      by surgery/anesthesia can be fatal.

PMID- 9186889
TI  - Renal lesions in rhabdomyolysis caused by Pseudechis australis snake myotoxin.
AB  - The renal lesions at various time intervals after i.m. injection of Pseudechis
      australis myotoxin (PA myotoxin) causing myoglobinuria in mice was studied.
      Biochemical assay of serum creatine phosphokinase (CK) and lactate dehydrogenase
      (LDH) showed marked elevations [7166 +/- 2064 IU and 1626 +/- 211 Berger-Broida
      U/ml (B-B U/ml)] six hours after injection, indicative of rhabdomyolysis. Serum
      creatinine (1.6 +/- 0.39) and urea (147 +/- 40) showed significant rise by 48
      hours indicative of acute renal failure (ARF). Immunodiffusion showed the
      presence of myoglobin in the urine (myoglobinuria) of experimental animals. Light
      microscopic (LM) and scanning electron microscopic (SEM) studies of the urinary
      sediments from experimental mice revealed granular casts of varying size and
      shape. LM of kidney showed casts from one hour and tubulopathy with degenerated
      tubular epithelial cell from 12 hours onwards. Focal glomerular changes, such as
      dilated Bowman's space with poorly stained substance and reduction in number of
      glomerular tufts were observed. Immunofluorescence microscopy for myoglobin
      showed fluorescence of the casts in the tubules. Transmission electron microscopy
      (TEM) showed electron dense casts occupying the entire lumen of the distal
      convoluted tubules (DCT). The proximal convoluted tubules (PCT) showed features
      of proximal tubular necrosis (PTN). There was reduction in the basal infolding
      with activation of lysosomal system in the PCT. The glomeruli showed changes in
      the visceral epithelium that included intracellular edema, vesiculation and
      occasional fusion of the podocytes. Numerous granular materials were observed in
      the Bowman's space as well as in the lumen of the capillaries from 1 to 24 hours.
      Electron dense deposits of the glomerular basement membrane (GBM) capillaries
      were observed from 1 to 24 hours. SEM study revealed loss of microvilli of the
      PCT and some tubular lumen were filled with cast like material. Some glomeruli
      displayed a relatively flattened podocytes with thickened major foot processes.
      Regeneration of the tubules were seen from three weeks onwards.

PMID- 9186888
TI  - Elevation of [Ca2+]i of renal proximal tubular cells and down-regulation of mRNA
      of PTH-PTHrP, V1a and AT1 receptors in kidney of diabetic rats.
AB  - An elevation in intracellular calcium ([Ca2+]i) in rats with chronic renal
      failure and elevated blood levels of PTH is associated with down-regulation of
      the mRNA of many proteins. Similarly, in phosphate depleted animals that have
      normal renal function and low blood levels of PTH, [Ca2+]i is elevated and the
      mRNA of PTH-PTHrP receptor is down-regulated. The effect of elevation in [Ca2+]i
      on molecular machinery of many proteins may represent a generalized phenomenon.
      Diabetes mellitus may also be associated with a rise in [Ca2+]i and therefore
      down-regulation of the mRNA of proteins may also occur. The present study
      examined the effect of streptozotocin-induced diabetes mellitus in rats on the
      [Ca2+]i of the renal proximal tubular cells and on their mRNAs of the PTH-PTHrP,
      V1a and AT1 receptors. The basal levels of [Ca2+]i of these cells increased
      significantly (P < 0.01) after one day of diabetes and remained elevated
      thereafter. There was a significant (r = 0.67, P < 0.01) direct correlation
      between the [Ca2+]i of the cells and blood levels of glucose up to 350 mg/dl, and
      the value of [Ca2+]i plateaued with higher concentrations of glucose. Three days
      of amlodipine therapy prevented and reversed the elevated levels of [Ca2+]i
      despite marked hyperglycemia. The mRNA of all three receptors in the kidney were
      down-regulated and this defect was prevented by amlodipine which normalized the
      [Ca2+]i of the cells. The results show that: (1) the hyperglycemia of IDDM in
      rats causes a significant elevation in the basal levels of [Ca2+]i of the renal
      proximal tubular cells and down-regulation of their mRNA of PTH-PTHrP, V1a and
      AT1 receptors; (2) normalization of the [Ca2+]i of these cells by treatment of
      the diabetic rats with amlodipine prevented the elevation of [Ca2+]i and the down
      regulation of the mRNA of these receptors; (3) these effects occurred in the
      presence of normal renal function and normal blood of PTH and phosphorus.

PMID- 9186891
TI  - Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis
      patients.
AB  - Leptin, the gene product of the ob gene, is important in the control of appetite
      in rodents and may have an important role in humans. The clearance of leptin from
      the circulation is unknown. As the leptin receptor is present in the kidney, we
      evaluated the role of the kidney in removing circulating leptin in humans. We
      measured leptin in aortic and renal vein plasma in 8 patients with intact renal
      function and 6 patients with impaired renal function who were undergoing elective
      cardiac catheterization. Renal blood flow was measured in all patients to
      calculate net mass balance across the kidney. In patients with intact renal
      function there is net renal uptake of 12% of circulating leptin, whereas in
      patients with renal insufficiency there is no renal uptake of leptin. In a
      separate cohort of 36 patients with end-stage renal failure on hemodialysis,
      peripheral leptin levels factored for body mass index was increased by > fourfold
      as compared to a group of healthy controls (N = 338). In addition, plasma leptin
      is not cleared by hemodialysis with a modified cellulose membrane. Additional
      studies are required to evaluate the role of leptin in mediating the anorexia of
      uremia.

PMID- 9186890
TI  - Modulation of growth factors by growth hormone in children with chronic renal
      failure. The Southwest Pediatric Nephrology Study Group.
AB  - Anthropometric measurements and circulating growth factors were studied serially
      in 44 prepubertal children with growth failure and chronic renal failure (GFR =
      10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human
      growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as
      Nutropin, 0.05 mg/kg/day, and the studies were carried out at baseline and after
      3 and 12 months. At baseline, serum insulin-like growth factor binding protein
      (IGFBP)-1 and -2 levels were, while IGFBP-3 levels were not, higher than those of
      children with normal renal function. In addition, height SDS at baseline
      correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0016), but did
      not correlate significantly with any other factor. After 12 months of study, the
      30 children receiving rhGH showed: (i) greater increase in height (9.1 +/- 2.8
      vs. 5.5 +/- 1.9 cm, P < 0.0001); (ii) increases in serum levels of IGF-I, IGF-II,
      free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in
      serum IGFBP-1 levels; and (iv) no significant difference in serum IGFBP-2 levels,
      when compared to the 14 control patients. The change in height SDS after 12
      months of rhGH (+0.8) in the 30 treated children correlated significantly and
      positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF-II and free IGF-I
      levels measured during treatment. These observations suggest that, in children
      with growth failure associated with chronic renal failure: (i) IGFBP-2, and not
      IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth
      in part by increasing serum levels of IGF peptides; and (iii) linear growth is
      influenced by the balance between growth stimulating IGFs and growth inhibitory
      IGFBPs.

PMID- 9186892
TI  - Splanchnic erythrocyte content decreases during hemodialysis: a new compensatory
      mechanism for hypovolemia.
AB  - Splanchnic and splenic erythrocyte volumes decrease during postural changes and
      exercise to help maintain central blood volume and cardiac output. The
      contribution of this compensatory mechanism to hemodynamic stability during
      dialysis has not been studied, however. In 8 ESRD patients, age 51.0 +/- 4.5
      years old, we measured changes in the splanchnic/splenic erythrocyte volume
      during dialysis by tagging the patients' erythrocytes with technetium and
      following abdominal radioactivity over time. Splanchnic radioactivity decreased
      to 90.2 +/- 3.8% (mean +/- SEM) of the baseline value after 2 hr of accelerated
      fluid removal (3.7 +/- 0.4 liters) during dialysis (DUF), while it remained
      relatively unchanged after two hours of dialysis without fluid removal (DD)
      [106.5 +/- 2.3%, P (DUF vs. DD) = 0.03]. Splenic radioactivity decreased to 89.2
      +/- 5.0% of the initial value during DUF versus 103 +/- 3.8% during DD, but the
      decrease was noted only during the last 30 minutes of DUF and did not attain
      statistical significance. Autonomic nervous system integrity was measured by the
      spontaneous variation of the R-R interval during deep respiration (E/I ratio) and
      by the Valsalva ratio. The mean E/I and Valsalva ratios in the eight patients
      were 1.13 +/- 0.03 (+/-SEM) and 1.42 +/- 0.1 respectively, suggesting reasonably
      adequate autonomic nervous system functioning. The results suggest that
      contraction of the splanchnic, and possibly the splenic, vascular beds occurs
      during fluid removal associated with hemodialysis. The resultant addition of
      erythrocytes to the circulation may help maintain central blood volume and
      cardiac output.

PMID- 9186893
TI  - Effect of calcitonin on calcium transport by the luminal and basolateral
      membranes of the rabbit nephron.
AB  - In the rabbit, calcitonin has been shown to enhance calcium (Ca2+) reabsorption
      in the early distal tubule. The aim of the present study was to investigate the
      mechanism of this action, using isolated luminal and basolateral membranes of
      distal tubules. The tubule suspensions were preincubated in the presence or
      absence of 10(-7) M calcitonin. The luminal or basolateral membranes were
      subsequently purified and 45Ca transport through the vesicles was measured using
      the rapid filtration technique. Results were compared with those obtained from
      proximal tubule membranes. In the proximal tubules, calcitonin had no effect on
      Ca2+ uptake by luminal membranes. In the distal tubules, the presence of Na+ in
      the incubation medium strongly decreased the uptake of Ca2+ by luminal membranes.
      Preincubation of distal tubules with calcitonin partially restored this uptake.
      We previously reported a dual kinetics of Ca2+ uptake by the distal luminal
      membranes. Calcitonin enhanced Ca2+ transport by the low affinity component,
      increasing the Vmax and leaving the K(m) unchanged. Renal calcitonin receptors
      usually couple to both adenylate cyclase and phospholipase C. To determine
      through which messenger(s) calcitonin enhances Ca2+ transport by the distal
      tubules, we first confirmed that the hormone stimulates cAMP and IP3 release.
      Incubation of the distal tubules with 10(-7) M calcitonin significantly increased
      both messengers. In contrast, calcitonin did not influence the IP3 nor the cAMP
      content of proximal tubules. Therefore, we studied the actions of cAMP and
      phorbol 12-myristate 13 acetate (PMA) on Ca2+ transport by the distal luminal
      membranes. Incubation of distal tubule suspensions with dibutyryl cAMP
      significantly increased Ca2+ uptake by the luminal membranes. However, incubation
      of these tubules with various concentrations of PMA (10 nM, 100 nM and 1 microM)
      had no effect on this uptake. Calcitonin also influenced Ca2+ transport by the
      distal basolateral membrane. Incubation of distal tubule suspensions with 10(-7)
      M calcitonin activated the Na+/Ca2+ exchanger activity, almost doubling the Na+
      dependent Ca2+ uptake. Here again this action was mimicked by cAMP. We conclude
      that calcitonin increases Ca2+ transport by the distal tubule through two
      mechanisms: the opening of low affinity Ca2+ channels in the luminal membrane and
      the stimulation of the Na+/Ca2+ exchanger in the basolateral membrane, both
      actions depending on the activation of adenylate cyclase.

PMID- 9186894
TI  - A simple and accurate method to determine equilibrated post-dialysis urea
      concentration.

PMID- 9186895
TI  - Immortalization and characterization of human peritoneal mesothelial cells.

PMID- 9186896
TI  - Hemodialyzer mass transfer-area coefficients for urea increase at high dialysate
      flow rates. The Hemodialysis (HEMO) Study.
AB  - The dialyzer mass transfer-area coefficient (KoA) for area is an important
      determinant of urea removal during hemodialysis and is considered to be constant
      for a given dialyzer. We determined urea clearance for 22 different models of
      commercial hollow fiber dialyzers (N = approximately 5/model, total N = 107) in
      vitro at 37 degrees C for three countercurrent blood (Qb) and dialysate (Qd) flow
      rate combinations. A standard bicarbonate dialysis solution was used in both the
      blood and dialysate flow pathways, and clearances were calculated from urea
      concentrations in the input and output flows on both the blood and dialysate
      sides. Urea KoA values, calculated from the mean of the blood and dialysate side
      clearances, varied between 520 and 1230 ml/min depending on the dialyzer model,
      but the effect of blood and dialysate flow rate on urea KoA was similar for each.
      Urea KoA did not change (690 +/- 160 vs. 680 +/- 140 ml/min, P = NS) when Qh
      increased from 306 +/- 7 to 459 +/- 10 ml/min at a nominal Qd of 500 ml/min. When
      Qd increased from 504 +/- 6 to 819 +/- 8 ml/min at a nominal Qh of 450 ml/min,
      however, urea KoA increased (P < 0.001) by 14 +/- 7% (range 3 to 33%, depending
      on the dialyzer model) to 780 +/- 150 ml/min. These data demonstrate that
      increasing nominal Qd from 500 to 800 ml/min alters the mass transfer
      characteristics of hollow fiber hemodialyzers and results in a larger increase in
      area clearance than predicted assuming a constant KoA.

PMID- 9186897
TI  - Blood transfusion during heparin-free hemodialysis.

PMID- 9186899
TI  - Presentation of the 1997 A.N. Richards Award to Alexander Leaf.

PMID- 9186898
TI  - Extrarenal manifestations of ADPKD.

PMID- 9186900
TI  - Presentation of the 1997 A.N. Richards Award to Klaus Thurau.

PMID- 9186901
TI  - Presentation of the 1997 Jean Hamburger Award to Renee Habib and Priscilla
      Kincaid-Smith.

PMID- 9186902
TI  - Lipoprotein lipase deficiency with pancreatitis in mink: biochemical
      characterization and pathology.
AB  - A severe hyperlipemia in mink, with a pattern that suggested recessive
      inheritance, was observed at a farm in Norway. On a normal mink diet, affected
      animals had grossly elevated levels of plasma triglycerides which decreased
      towards normal on a low-fat diet. Normal minks had the main part of their plasma
      cholesterol in the HDL fraction. Affected minks, although severely
      hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected
      minks frequently had lipogranulomas in the mesentery and the pancreas. The
      lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic
      substance with many foamy macrophages in the fibrous tissue between the lesions.
      Separation of postheparin plasma on heparin-agarose revealed that the affected
      minks had no detectable lipoprotein lipase activity but normal activity of
      hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase
      protein in pre- and post-heparin plasma. This protein, which eluted before the
      active lipase from heparin-agarose, probably corresponds to lipase monomers. The
      presence of lipoprotein lipase mass in the affected minks, but no activity,
      indicates that there might be a point mutation in the lipase gene. The minks
      provide a new animal model for studies on pancreatitis induced by
      hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase
      deficient state and show features similar to those found in human
      hyperlipoproteinemia type I.

PMID- 9186903
TI  - Characterization of the human apobec-1 gene: expression in gastrointestinal
      tissues determined by alternative splicing with production of a novel truncated
      peptide.
AB  - In humans, both the expression of apobec-1 and the C to U deamination of apoB
      mRNA are confined to the small intestine. In order to understand the tissue
      restricted pattern of apobec-1 expression, we have isolated the chromosomal gene
      spanning the human apobec-1 locus. The human apobec-1 gene spans 18 kb and
      contains five exons, all of which are translated. Transcription initiation,
      determined by RNase protection and primer extension analyses, is localized to a
      single start site 34 nt upstream of the open-reading frame in exon 1. A common,
      but functionally silent, gene polymorphism was detected than changes Ilc80 to
      MCl. RNase protection and reverse-transcription PCR analysis demonstrated the
      presence of an exon 2-skipped form of apobec-1 mRNA that arises through use of an
      alternative splice acceptor. This alternative splicing causes a frame-shift that
      produces a novel, 36 amino acid peptide. The exon 2-skipped form accounts for
      approximately 50% of apobec-1 mRNA in the adult small intestine and up to 90% of
      apobec-1 mRNA in the developing gut. An antipeptide antibody identified the
      truncated protein in villus cells of the adult small intestine. These data
      suggest that exon 2-skipping may represent an important control mechanism
      regulating apobec-1 gene expression in humans.

PMID- 9186904
TI  - Linoleic acid enhances the secretion of plasminogen activator inhibitor type 1 by
      HepG2 cells.
AB  - This study was undertaken in order to assess whether triglycerides and/or their
      fatty acids directly influence the secretion of plasminogen activator inhibitor
      type 1 (PAI-1) in HepG2 cells. To this end, subconfluent HepG2 cells were
      incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16
      h, and PAI-1 levels were determined in conditioned medium using a specific ELISA.
      TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1
      secretion by cells, concomitantly with significant increases in intracellular
      triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of
      cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6
      (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid
      composition at the added triglycerides. We then tested the comparative effects on
      PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a
      bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L)
      increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected
      it at the highest concentration used (35 mumol/L). Incorporation of LA into cell
      pools, in the presence of increasing concentration of the FA in the medium, was
      studied by the use of a preparation containing [14C]LA. LA accumulated in all
      lipid classes including diacylglycerol, the incorporated LA being converted into
      arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid
      methyl esters. It is concluded that PAI-1 secretion in HepG2 cells is modulated
      by triacylglycerols and by linoleic acid and/or its metabolic products.

PMID- 9186905
TI  - Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase
      gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from
      two unrelated families.
AB  - The autosomal recessively inherited cholesterol metabolic disease,
      cerebrotendinous xanthomatosis (CTX), is caused by mutations in the sterol 27
      hydroxylase gene. Three Japanese CTX patients from two unrelated families were
      studied genetically. By DNA sequence analysis a novel mutation of A for G
      substitution at amino acid position 372 (CGG 372Arg to CAG 372Gln) was identified
      in one of the CTX families. The mutation was also found in two patients from the
      other family, with a compound heterozygous pattern of A for G substitution at
      amino acid position 441 (CGG 441Arg to CAG 441Gln). The latter mutation was the
      same as previously reported by our group (J. Lipid Res. 1994. 35: 1031-1039). As
      the two mutations changed the restriction enzyme sites, rapid screening methods
      were developed for the detection of the carriers. Transfection of the two mutant
      cDNAs into COS cells resulted in markedly reduced sterol 27-hydroxylase activity.
      These results indicate that the two mutations are responsible for the deficiency
      of the sterol 27-hydroxylase activity in these patients. The features of
      mutations identified till now in Japanese CTX patients are also reviewed.

PMID- 9186906
TI  - The acid lipase gene family: three enzymes, one highly conserved gene structure.
AB  - Human gastric lipase (HGL; triacylglycerol lipase; EC 3.1.1.3) plays an important
      role in the digestion of dietary triglycerides in the gastrointestinal tract,
      especially in patients suffering from pancreatic lipase deficiencies. The enzyme
      is secreted by the fundic mucosa of the stomach and hydrolyzes the ester bonds of
      triglycerides under acidic pH conditions, while cholesteryl esters are not
      attacked. The 379-amino acid protein is highly homologous to two other acidic
      lipases, rat lingual lipase (RLL; triacylglycerol lipase; EC 3.1.1.3) and human
      lysosomal acid lipase (HLAL; cholesteryl esterase; EC 3.1.1.13). To determine
      whether this remarkable similarity is also present at the genomic level, we have
      elucidated the respective gene structures by screening three bacteriophage lambda
      libraries and by polymerase chain reaction-based intron amplification. The genes
      encoding HGL, RLL, and HLAL are composed of 10 exons interrupted by nine introns
      and span about 14 kb, 18.7 kb, and 38.8 kb of genomic DNA, respectively. The HGL
      and RLL gene organizations are identical, suggesting that RLL is the rat gastric
      lipase expressed in the serous von Ebner glands of the tongue. The positions of
      the HLAL intervening sequences are also absolutely conserved, except for the
      location of intron 1. Our results support the concept that HLAL and HGL/RLL are
      members of a gene family of lipases that most likely have evolved by duplication
      of an ancestral gene and subsequently assumed distinct roles in neutral lipid
      metabolism due to sequence divergence and different expression patterns.

PMID- 9186907
TI  - Human lysosomal acid lipase/cholesteryl ester hydrolase and human gastric lipase:
      identification of the catalytically active serine, aspartic acid, and histidine
      residues.
AB  - Human lysosomal acid lipase/cholesteryl ester hydrolase (HLAL), human gastric
      lipase (HGL), and rat lingual lipase (RLL) constitute a family of mammalian
      lipases characterized by an acidic pH optimum. HGL and RLL are secreted by the
      chief cells of the stomach and by the serous von Ebner's glands of the tongue,
      respectively, and hydrolyze dietary longchain triglycerides in the
      gastrointestinal tract. HLAL, in contrast, catalyzes the intralysosomal
      degradation of both triglycerides and cholesteryl esters in virtually all cells
      except erythrocytes. All three enzymes are proposed to be serine esterases with a
      catalytic Ser-Asp-His triad similar to other lipases, despite their sensitivity
      towards sulfhydryl modifying reagents. To investigate the role of conserved
      serine, aspartic acid, and histidine residues in HLAL and HGL, we constructed 24
      mutant lipases with single amino acid substitutions using the site-directed
      mutagenesis approach. Our combined data strongly support the conclusion that
      Ser153, Asp324, and His355 are components of the catalytic triad of HLAL and HGL.
      Structural integrity of the conserved His-Gly dipeptide of lipases also appears
      to be important for neutral lipid hydrolysis, as replacement of His65 by
      glutamine abolished HLAL and HGL enzymic activity. Substitution of HLAL residues
      Asp93, Asp130, and Asp328 with glycine, in contrast, had a more pronounced impact
      on cholesteryl oleate hydrolysis than on triglyceride hydrolysis. These results
      provide new insights into the structural basis of HLAL and HGL function.

PMID- 9186908
TI  - Combined effects of lipoprotein lipase and apolipoprotein E polymorphisms on
      lipid and lipoprotein levels in the Stanislas cohort.
AB  - We have genotyped 1101 supposedly healthy subjects from the Stanislas cohort for
      the lipoprotein lipase (LPL) gene Ser417(C)-->stop (G) polymorphism and/or for
      the apolipoprotein (apo)E common polymorphism. Genotypic effects of the two
      polymorphisms on fasting serum triglycerides (TG), total cholesterol (Tchol),
      high density lipoprotein-cholesterol (HDLc), low density lipoprotein-cholesterol
      (LDLc), apoB, apoA-I, and apoE levels were studied separately for each
      polymorphism and in conjunction. epsilon 4 allele and high apoE levels were
      associated with high levels of LDLc, Tchol, apoB, and TG. The G allele of LPL was
      significantly associated with low TG levels. We found a clear interaction between
      the LPL/apoE polymorphisms and apoE levels on serum TG variation. Total
      variability of TG levels in women and men of 42.31% and 53.62% respectively, were
      mainly explained by apoE concentration and these two polymorphisms. ApoE and LPL
      genes simultaneously modulated TG levels.

PMID- 9186909
TI  - Lipid-depleted diet perturbs membrane composition and intracellular transport in
      lactating mammary cells.
AB  - When rats were fed a control or a lipid-depleted diet for five generations,
      reproduction was not disturbed but pup growth was affected. The membrane
      organization and the secretory activity of mammary epithelial cells from these
      lactating rats were investigated. This diet induced a large decrease in the level
      of polyunsaturated fatty acids of membrane phospholipids (26.6% versus 44.0%).
      The level of 20:4 (n-6) was strongly decreased, mainly in
      phosphatidylethanolamine. Annexin VI, which interacts preferentially with this
      phospholipid, accumulated at the periphery of the cell and was largely associated
      to the hydrophobic region of the bilayer as compared to control membranes. Casein
      synthesis and casein secretion measured in incubated explants, after pulse-chase
      metabolic labeling, were both reduced by about 60% in lipid-deprived cells. The
      secretory ratio (radioactive secreted caseins in %) was not modified, suggesting
      that the mechanism of basal secretion was not mainly affected. On the contrary,
      the secretagogue effect of prolactin disappeared. The intracellular transport of
      the hormone was considerably slowed down by the diet and prolactin did not reach
      the lumen of the acini after 1 h of chase, in contrast to what occurred in
      control cells. Addition of 20:4 (n-6), in vitro, to mammary fragments from lipid
      deprived rats restored the localization of annexin VI, increased synthesis and
      secretion of caseins as well as intracellular transport of PRI. Together, these
      data underline the importance of the level of 20:4 (n-6) in membrane
      phospholipids for exocytic and endocytic transport in lactating mammary
      epithelial cells.

PMID- 9186910
TI  - High levels of (24S)-24-hydroxycholesterol 3-sulfate, 24-glucuronide in the serum
      and urine of children with severe cholestatic liver disease.
AB  - Extracts of urine and serum from children with cholestatic liver disease were
      analyzed by fast atom bombardment (FAB) mass spectrometry. About half of all
      spectra showed a peak at m/z 657, compatible with the presence of a
      glucuronidated cholestenediol sulfate. Separation by ion exchange chromatography
      before and after solvolysis and treatment with beta-glucuronidase, combined with
      analyses by gas chromatography-mass spectrometry and FAB mass spectrometry with
      collision-induced dissociation, showed that the major compound responsible for
      the peak at m/z 657 was (24S)-24-hydroxycholesterol 3-sulfate, 24-glucuronide.
      The double conjugate of 27-hydroxycholesterol was also identified and double
      conjugates of cholestene- and cholestanetriols were also present.
      Semiquantitative analyses of the double conjugate of 24-hydroxycholesterol in
      patients whose FAB spectra showed a peak at m/z 657 indicated serum levels of 2
      18 microM and a daily urinary excretion of 0.1-2.7 mumol/24 h. Eleven of 13
      studied patients with a prominent peak at m/z 657 in the FAB spectra of their
      serum or urine either underwent liver transplantation or died. It is concluded
      that double conjugation of hydroxysterols with sulfuric and glucuronic acids can
      be an important metabolic pathway, particularly for (24S)-24-hydroxycholesterol.
      It is speculated that serious cholestatic liver disease may induce an increased
      formation and release of (24S)-24-hydroxycholesterol from brain (Lutjohann et al.
      1996, Proc. Nutl. Acad. Sci. USA. 93: 9799-9804) with subsequent extracerebral
      conjugation with sulfuric and glucuronic acids.

PMID- 9186911
TI  - Uptake of 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-cholan-23-sulfonate
      into isolated rat hepatocytes by three transport systems.
AB  - Uptake of norcholansulfonate (3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta
      cholan-23-sulfonate), an isogeometric analogue of cholate into isolated rat liver
      hepatocytes occurs only by saturable transport. In order to identify the
      transport systems involved, uptake of norcholansulfonate was studied using 7 beta
      NBD-NCT ({N-[7-(4-nitrobenzo-2-oxa-1,3-diazol)]-7 beta-amino-3 alpha,12 alpha
      dihydroxy-5 beta-cholan-24-oyl})-2'-aminoethanesulfonate) as a competing
      substrate. For transport of both bile salt derivatives, which mutually inhibit
      their mediated transport competitively, the existence of at least three transport
      systems must be assumed. Uptake studies using the cloned hepatic
      Na+/cholyltaurine cotransporting polypeptide stably expressed in CHO cells
      (Chinese hamster ovary cells) showed that both bile salt derivatives were
      transported and furnished the definite KT values of this single transport system
      and the ratio of the maximal uptake velocities. On the basis of these data,
      uptake of both bile salt derivatives into rat hepatocytes and their mutual
      competitive inhibition could be analyzed for three transport systems. The maximal
      flux rates J2 and the half-saturation constants KT2 in the presence of Na+ (143
      mM) are for norcholansulfonate: J1(Na+ 143) = 1.0 +/- 0.2 nmol/(min . mg
      protein), KT1(Na+ 143) = 15 +/- 4 microM, J2(Na+ 143) = 0.5 +/- 0.2 nmol/(min.mg
      protein), KT2(Na+ 143) = 15 +/- 2 microM, J3(Na+ 143) = 0.5 +/- 0.2 nmol/(min.mg
      protein), KT3(Na+ 143) = 60 +/- 15 microM, and for 7 beta-NBD-NCT J1(Na+ 143) =
      0.14 +/- 0.04 nmol/(min.mg protein), KT1(Na+ 143) = 3.1 +/- 0.5 microM, J2(Na+
      143) = 0.014 +/- 0.005 nmol/(min.mg protein), KT2(Na+ 143) = 21 +/- 2 microM,
      J3(Na+ 143) = 1.0 +/- 0.1 nmol/(min.mg protein), KT3(Na+ 143) = 190 +/- 25
      microM. The kinetic parameters are in accordance with the assumptions that the
      cloned Na+/cholyltaurine cotransporting polypeptide represents transport system 2
      and that the kinetically identified additional transport system 1 is either
      strictly or partially Na(+)-dependent.

PMID- 9186912
TI  - Chylomicron/chylomicron remnant turnover in humans: evidence for margination of
      chylomicrons and poor conversion of larger to smaller chylomicron remnants.
AB  - The size of cholesterol-rich lipoprotein particles is a strong determinant of
      whether they may be deposited in the arterial wall and by this become potentially
      atherogenic. This study deals with the in vivo transformation of larger-sized
      chylomicrons and chylomicron remnants to smaller-sized remnants. Twelve healthy
      men aged 22 to 45 years were given a fatty meal to which retinyl palmitate (RP)
      had been added. Plasmapheresis was performed 4 1/2 h after meal intake to isolate
      approximately 400 ml plasma. The RP-rich plasma was re-injected to the subject 24
      h later. The RP content was determined in whole plasma and in Svedberg flotation
      rate fractions (Sf) > 400, Sf 60-400 and Sf 20-60. A compartmental model was
      developed for the kinetic analysis. Lipoprotein fractions showed minimal signs of
      aggregation, thus arguing for well-preserved postprandial lipoproteins.
      Approximately a fourth [23% (4-68%)] of the RP-containing lipoproteins in the Sf
      > 400 pool was converted to smaller species (Sf 60-400). Conversion of material
      from the Sf 60-400 to the Sf 20-60 fraction could not be detected. In a second
      study a large bolus dose of a triglyceride emulsion (Intralipid) was injected to
      subjects shortly after the RP-labeled plasma to investigate the endothelial
      binding of the chylomicron/chylomicron remnants. RP material in the Sf > 400
      fraction rapidly returned to plasma, arguing for margination of chylomicrons,
      whereas the corresponding effect was minimal in the Sf 60-400 and Sf 20-60
      fractions. The formation of small chylomicron remnants from the larger
      chylomicron/chylomicron remnant species is limited and large
      chylomicron/chylomicron remnants are not evenly distributed in plasma, rather
      they show signs of being marginated to the vascular endothelium.

PMID- 9186913
TI  - Polyprenol formation in the yeast Saccharomyces cerevisiae: effect of farnesyl
      diphosphate synthase overexpression.
AB  - Biosynthesis of polyprenols was followed in the erg mutants of Saccharomyces
      cerevisiae impaired in various steps of the mevalonate pathway. The end products
      of the enzymatic reaction carried out in vitro, in the wild type yeast and all
      mutants tested, were identified as dehydrodolichols (alpha-unsaturated
      polyprenols) whereas in vivo, yeast synthesize dolichols (alpha-saturated
      polyprenols) (Biochimie, 1996.78:111-112.) The strain defective in the farnesyl
      diphosphate (FPP) synthase, (coded by the erg20-2 gene) required the presence of
      exogenous FPP for synthesis of dehydrodolichols to occur in vitro. Overexpression
      of the ERG20 gene restored synthesis of polyprenols in vitro indicating that FPP
      is the allylic "starter" for cis-prenyltransferase in yeast. Overexpression of
      the ERG20 gene in the erg 9 mutant, defective in squalene synthase activity, not
      only restored synthesis of dehydrodolichols in vitro, but also increased the
      synthesis of dolichols in vivo, almost 10-fold in comparison with wild type
      yeast. On the other hand overexpression of the mutated FPP synthase, coded by the
      gene erg20-2 in the same genetic background, resulted in a 100-fold increase of
      the amount of dehydrodolichols. Interestingly, in addition to the family of
      typical for yeast C60-C80 compounds, dehydrodolichols of chain length up to C135
      were synthesized both in vitro and in vivo.

PMID- 9186914
TI  - Evidence for the existence of ganglioside-enriched plasma membrane domains in
      human peripheral lymphocytes.
AB  - In human peripheral blood lymphocytes (PBL) monosialoganglioside GM3 appears to
      be the major ganglioside on the cell plasma membrane. We have analyzed the
      expression and distribution pattern of GM3 molecules on the lymphocyte plasma
      membrane by flow cytometry, immunofluorescence, and immunoelectron microscopy,
      using an anti-GM3 monoclonal antibody. Both CD4+ and CD8+ T lymphocyte
      subpopulations showed substantial GM3 expression, as determined by thin-layer
      chromatography and flow cytometric analysis. A clustered distribution of GM3
      molecules on the cell surface, revealed by immunofluorescence and immunogold
      electron microscopy, clearly indicated the presence of GM3 molecule-enriched
      plasma membrane domains. To better define these domains, we analyzed the
      ganglioside and protein composition of buoyant low-density Triton-insoluble
      (LDTI) lymphocyte fractions. The results show that GM3 is enriched approximately
      20-fold in LDTI fraction, as compared with total cell lysates. In addition, CD4
      and lck molecules are selectively recovered in the same LDTI fraction isolated
      from human PBL. These findings, together with the observation that anti-CD4 co
      immunoprecipitated GM3, support the hypothesis of a possible GM3-CD4 interaction
      and suggest a role for gangliosides as structural components of the membrane
      multimolecular signaling complex involved in T-cell activation, antigen
      recognition, and other dynamic lymphocytic plasma membrane functions.

PMID- 9186915
TI  - Mechanisms of enhanced macrophage apoE secretion by oxidized LDL.
AB  - Previous studies have demonstrated that atherosclerotic lesions contain apoE
      synthesized primarily by macrophages. As oxidized LDL has been implicated in the
      development of atherosclerosis, its effect on macrophage apoE synthesis and
      secretion was examined. Human monocytic leukemia cells, THP-1, and human monocyte
      derived macrophages were exposed to various forms of oxidatively modified LDL for
      determination of their effect on apoE mRNA and protein levels. Extensively copper
      oxidized (Cu-oxidized) LDL resulted in a time- and concentration-dependent
      increase in apoE mRNA and protein as compared to other forms of oxidized LDL,
      i.e., LDL modified by soybean lipoxygenase (SLO), azoamidinopropane HCl (AAPH),
      and hypochlorite (HOCl). Consistent with these results, experiments using THP-1
      cells transfected with the apoE promoter linked to a luciferase reporter gene
      indicated that Cu-oxidized LDL was the most potent stimulator of apoE transgene
      expression. Enhanced apoE expression due to Cu-oxidized LDL was shown to be due
      to cholesterol accumulation as well as additional factors. HPLC analysis of the
      various forms of modified LDL revealed that 7-ketocholesterol was the major
      oxysterol present in Cu-oxidized LDL. AAPH-oxidized LDL contained significantly
      less 7-ketocholesterol than Cu-oxidized LDL and virtually no 7-ketocholesterol
      was detected in SLO- or HOCl-oxidized LDL. Northern blot analysis indicated an
      increase in apoE mRNA in response to increasing concentrations of 7
      ketocholesterol. These results elucidate a potential role of oxidized LDL, and
      specifically 7-ketocholesterol, in the stimulation of macrophage apoE secretion
      in atherosclerotic lesions.

PMID- 9186916
TI  - Comparison between copper-mediated and hypochlorite-mediated modifications of
      human low density lipoproteins evaluated by protein carbonyl formation.
AB  - The purpose of this study was to evaluate the mechanisms of apolipoprotein B
      (apoB) modification during oxidation of human low density lipoproteins (LDL)
      mediated either by copper or by hypochlorite (HOCl). The kinetics of protein
      carbonyl formation, the relationship of apoB carbonyl formation to lipid
      peroxidation, and the loss of apoB lysine residues were determined. During copper
      mediated LDL oxidation, apoB carbonyls appeared to increase slowly, displayed
      saturation kinetics in response to increasing copper concentrations, and
      correlated with lipid peroxidation. During HOCl-mediated LDL oxidation, apoB
      carbonyls increased with increasing HOCl concentrations reaching plateau with
      time; however, lipid peroxidation was not observed. During copper-mediated but
      not during HOCl-mediated LDL oxidation, LDL vitamin E was depleted. ApoB
      carbonyls formed more efficiently during copper-mediated LDL oxidation at low (<
      5 microM) copper concentrations compared with higher copper concentrations or
      during HOCl-mediated LDL oxidation. The differences in oxidation kinetics between
      copper- and HOCl-mediated LDL oxidation support the concept that the binding of
      copper to LDL is a site specific process, and suggest that HOCl modifies apoB
      amino acids randomly.

PMID- 9186917
TI  - Hepatic lipase is abundant on both hepatocyte and endothelial cell surfaces in
      the liver.
AB  - The cellular location of hepatic lipase was investigated in transgenic rabbits
      that expressed human hepatic lipase in the liver. The binding of monoclonal
      antibodies to human hepatic lipase, as detected by either fluorescence-tagged or
      gold-conjugated secondary antibodies, showed that hepatic lipase was concentrated
      at the surfaces of hepatic sinusoids. This distribution was the same as observed
      in the human liver. At the ultrastructural level, immunogold labeling of the
      space of Disse showed hepatic lipase on both lumenal and sublumenal surfaces of
      rabbit liver sinusoidal endothelial cells. An equivalent amount of hepatic lipase
      also was found on the external surfaces of hepatocyte microvilli in the space of
      Disse, as well as in the interhepatocyte spaces. The distribution suggests that a
      majority of the hepatic lipase produced by the liver is associated with
      hepatocyte surfaces, consistent with the functions of this enzyme in lipoprotein
      metabolism.

PMID- 9186918
TI  - X-ray crystal structure of cytotoxic oxidized cholesterols: 7-ketocholesterol and
      25-hydroxycholesterol.
AB  - The cytotoxic cholesterol derivative, 7-ketocholesterol, crystallizes in a
      monoclinic unit cell, space group P2(1) with a = 11.405 A, b = 6.288 A, c =
      35.393 A and beta = 92.75 degrees (Z = 4). Its room temperature crystal structure
      was solved by direct methods, i.e., the minimal principle via the Shake-and-Bake
      (SnB) algorithm. In contrast to the continuous chain pattern found for the
      cholesterol monohydrate structure, hydrogen bonding in the 7-ketocholesterol
      structure is localized to specific sites via one water molecule that forms
      linkages between two O3 hydroxyl groups and one keto oxygen. The final weighted R
      factor for 4562 reflections was 0.144. The 25-hydroxycholesterol also
      crystallizes in a monoclinic unit cell (P2(1)), with a = 10.840 A, b = 14.533 A,
      c = 16.093 A and beta = 95.91 degrees (Z = 4). The low temperature structure was
      solved by DIRDIF. In this instance, molecular packing is anti-parallel in layers
      stabilized by hydrogen bonding networks via both hydroxyl functions, differing
      both from cholesterol monohydrate and the 7-ketocholesterol. The final weighted R
      factor for 6566 reflections was 0.034. Functional differences of the oxysterols
      therefore, may be expressed by observed variations in the molecular packing and
      geometry.

PMID- 9186919
TI  - Synthesis and characterization of a new bile acid and platinum(II) complex with
      cytostatic activity.
AB  - With a view to using bile acids as shuttles for delivering platinum-related
      cytostatic drugs to the liver, a cholylglycine(CG)-derivative of platinum(II) has
      been synthesized. The complex, named Bamet-H2, was characterized by elemental
      analysis, FT-IR, NMR, FAB-MS, and UV spectroscopy. The results indicate the
      following composition: C52H84N2O12ClNa Pt(II). Conductivity data suggest that the
      complex behaves as a sodium salt (1:1) of a complex of Pt(II) bound to one cl-,
      one bidentate CG moiety, and another monodentate CG moiety, i.e., Na[Pt(CG
      O,N)(CG-O)Cl]. The compound is highly soluble (up to 10 mM) in water, ethanol,
      methanol, DMF, and DMSO. Bamet-H2 was stable in solution (either water or 150 mM
      NaCl solution), as measured by HPLC, up to 24 h. At this time, more than 90% of
      the platinum present in water or saline solutions was found to be Bamet-H2.
      Cytostatic activity against L1210 murine leukemia cells was found. This
      characteristic was stronger against rat hepatocytes in primary culture. Isolated
      in situ rat livers were perfused for 40 min with a recirculating medium
      containing 1 microM Bamet-H2, CG, or cisplatin. Uptake and excretion into bile
      were much greater for Bamet-H2 than for cisplatin, but less than for CG. Liver
      content was higher for Bamet-H2 than for cisplatin or CG. The results point to
      the potential usefulness of Bamet-H2 in the antitumoral therapy of neoplasias
      derived from liver parenchymal cells.

PMID- 9186920
TI  - ApoA-I knockout mice: characterization of HDL metabolism in homozygotes and
      identification of a post-RNA mechanism of apoA-I up-regulation in heterozygotes.
AB  - The major high density lipoprotein (HDL) apolipoprotein, apoA-I, was knocked out
      by gene targeting in ES cells to provide a model for the study of HDL metabolism
      and its relationship to plasma and tissue cholesterol metabolism. HDL and non-HDL
      cholesterol (HDL-C) were reduced in apoA-I-deficient mice. Feeding a high fat
      high cholesterol diet raised HDL-C minimally in apoA-I knockout compared to the
      large increase seen in control mice, suggesting an interaction between diet and
      apoA-I genotype. In apoA-I-deficient mice, HDL was normal in size but altered in
      composition. Compared to control mice there was more triglyceride and free
      cholesterol and less cholesteryl ester (CE), suggesting that apoA-I-deficient HDL
      is a poor substrate for hepatic lipase and lecithin:cholesterol acyltransferase
      (LCAT). The metabolic basis of the low HDL-C levels in the apoA-I knockout mice
      was decreased flux into the HDL CE pool. The absolute delivery of HDL CE to both
      peripheral tissues and liver was also decreased. As tissue cholesterol levels and
      synthesis were unchanged, the decreased flux of cholesterol into the HDL CE pool
      was most likely due to decreased efflux of cholesterol from the peripheral
      tissues and decreased functional LCAT activity. The low HDL-C state in the apoA-I
      deficient mouse was associated with an absolute decrease in unidirectional
      transport of cholesterol from peripheral tissues to the liver but this did not
      lead to cholesterol accumulation in the periphery or a cholesterol deficit in the
      liver; nor was there altered peripheral tissue HMG-CoA reductase activity. The
      only sign of decreased cholesterol flux to the liver was a 2.3-fold decrease in
      liver cholesterol 7 alpha-hydroxylase mRNA, suggesting decreased bile acid
      synthesis. In the apoA-I knockout mouse model it appears that low HDL levels
      create a new steady state in which decreased cholesterol is delivered to both
      peripheral tissues and the liver.

PMID- 9186921
TI  - A new method for the rapid measurement of cholesterol crystallization in model
      biles using a spectrophotometric microplate reader.
AB  - Measurements of the cholesterol crystal observation time, and particularly the
      crystal growth rate in model biles, are important in biliary pathophysiology. The
      aim of this study was to develop a semi-automated method permitting multiple,
      simultaneous, and precise measurements of the crystal growth rate in model biles.
      Incubated model biles were mixed with a high concentration of NaTDC to solubilize
      non-crystalline turbidity and spectrophotometric measurements were performed. In
      parallel, samples were observed by light microscopy. The absorbance correlated
      linearly with the crystal mass and permitted quantitation of the crystal growth
      rate. Polarized light microscopy was more sensitive than spectrophotometry for
      determining the initial crystal observation time, while spectrophotometry was
      more precise and quantitative for measuring the crystal growth rate.

PMID- 9186922
TI  - 7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation
      of cholesterol synthesis.
AB  - The report of a novel cytochrome P450 enzyme in mouse hippocampus (cyp7b) with
      close homology to cholesterol 7 alpha-hydroxylase led us to determine the
      substrate specificity with respect to 27-hydroxycholesterol, known to be a potent
      inhibitor of cholesterol synthesis. Transfection of 293/T-cells with PcDNA3.1(+)
      mcyp7b was followed by metabolism of 2.5 microM 27-hydroxycholesterol to the 7
      alpha-hydroxy intermediate, cholest-5-ene,3 beta,7 alpha,27-triol, with complete
      loss of down-regulation of cholesterol synthesis. Addition of 5 microM and 10
      microM concentrations of the triol to HepG2 and CHO cells, respectively, also did
      not reduce cholesterol synthesis. The contrast between the biologic effect on
      cholesterol synthesis by these two C27 hydroxysterols and the wide tissue
      distribution of both cholesterol 27-hydroxylase and hydroxysterol 7 alpha
      hydroxylase implies local regulatory effects prior to their further catabolism in
      the liver to chenodeoxycholic and cholic acids.

PMID- 9186923
TI  - Bioethics, metaphysical involvements, and biomedical practice.

PMID- 9186924
TI  - Levinas and the Hippocratic oath: a discussion of physician-assisted suicide.
AB  - At least from the standpoint of contemporary cultural and ethical resources,
      physicians have argued eloquently and exhaustively both for and against physician
      assisted suicide. If one avoids the temptation to ruthlessly simplify either
      position to immorality or error, then a strange dilemma arises. How is it that
      well educated and intelligent physicians, committed strongly and compassionately
      to the care of their patients, argue adamantly for opposing positions? Thus
      rather than simply rehashing old arguments, this essay attempts to rethink the
      nature of human morality as both a source and a fracturing of human rationality-
      and with morality, the question of human nature in the context of violence,
      oppression, service, and obligation. This interpretation of moral life is laid
      out roughly along the lines of the Jewish philosopher Emmanuel Levinas, and
      further clarified through a discussion of the Hippocratic Oath. These resources
      are then brought to bear on the specific arguments and recommendations concerning
      physician-assisted suicide.

PMID- 9186925
TI  - Can enhancement be distinguished from prevention in genetic medicine?
AB  - In discussions of the ethics of human gene therapy, it has become standard to
      draw a distinction between the use of human gene transfer techniques to treat
      health problems and their use to enhance or improve normal human traits. Some
      dispute the normative force of this distinction by arguing that it is undercut by
      the legitimate medical use of human gene transfer techniques to prevent disease
      such as genetic engineering to bolster immune function, improve the efficiency of
      DNA repair, or add cellular receptors to capture and process cholesterol. If
      disease prevention is a proper goal of medicine, these critics argue, and the use
      of gene transfer techniques to enhance human health maintenance capacities will
      help achieve that goal, then the "treatment/enhancement" distinction cannot
      define the limits of legitimate gene therapy. In this paper, I argue that a line
      can be drawn between prevention and enhancement for gene therapy (and thus
      between properly medical and nonmedical uses of gene therapy), but only if one is
      willing to accept two rather old-fashioned claims: 1) Some health problems are
      best understood as if they were entities in their own right, reifiable as
      processes or parts in a biological system, with at least as much ontological
      objectivity and theoretical significance as the functions that they inhibit. 2)
      Legitimate preventive genetic health care should be limited to efforts to defend
      people from attack by these more robust pathological entities, rather than
      changing their bodies to evade social injustices.

PMID- 9186926
TI  - Health as a normative concept: towards a new conceptual framework.
AB  - One of the main concerns in defining health is determining its status in relation
      to value. The main proposals in this direction generally assume a strict
      dichotomy between descriptive and evaluative dimensions. This essay argues that
      such a dichotomy leads to a theoretical inconsistency, which becomes evident once
      a definition of health is practically operative. A new conceptual framework
      uniting these two moments is proposed as an alternative, capable of preserving
      the fundamental insights of both descriptive and evaluative accounts of health,
      and of avoiding the theoretical inconsistencies on the level of practical
      application.

PMID- 9186927
TI  - The other human-subject experiments.
AB  - Although deceptive psychology experiments receive less attention than some forms
      of medical research, they pose similar moral challenges. These challenges mainly
      concern the use of human subjects and intentional deception. Psychologists
      provide an argument to justify this deception. But what is an essentially
      utilitarian argument too often includes faulty comparisons and dubious accounts
      of risks and benefits. Commentators in other areas of human-subject research
      might examine this argument and the assumptions behind it. Bioethics commentators
      seem especially well-positioned for this task.

PMID- 9186928
TI  - Degrees of personhood.
AB  - In this paper I argue that a Naturalist conception of personhood, such as the one
      defended by Derek Parfit, implies that there are degrees of personhood, i.e.,
      that it makes sense to say one individual has a greater degree of personhood than
      another. I describe both criteria of general personhood, which distinguish
      between persons and non-persons, and criteria of particular personhood, which
      distinguish between one person and another. I examine some of the consequences
      for ethics, including the rights to life, self-determination, and treatment.
      There may be circumstances in medicine where we have to judge the value of a
      patient's life in order to decide what medical treatment, if any, to provide, and
      although it may be emotionally difficult and politically dangerous, one relevant
      factor is what degree of personhood that individual has.

PMID- 9186929
TI  - Suspected calcium oxalate raphide irritation in a black rhinoceros (Diceros
      bicornis) due to ingestion of Xanthosoma mafaffa.

PMID- 9186930
TI  - Suspected aflatoxicosis in breeding budgerigars.

PMID- 9186931
TI  - The possible role of manganese poisoning in enzootic geophagia and hepatitis of
      calves and lambs.

PMID- 9186933
TI  - Effect of different bedding materials on the reproductive performance of mice.
AB  - Vermiculite, pine shavings and unbleached eucalyptus pulp contact-bedding were
      compared using the number of litters and individuals born and weaned, mortality
      rates at different stages of the lactation period, and the weight increase of
      pups as evaluation indices for bedding quality. These bedding materials exerted
      different effects on the reproductive performance of the same mouse strain. The
      same is true for the effect of a specific bedding material on different mouse
      strains. These effects are most pronounced during the first 4 days of life. As a
      whole, the results demonstrated that eucalyptus pulp was the better bedding type,
      followed by pine shavings and vermiculite. The latter material had a detrimental
      effect on the mating success of AKR mice.

PMID- 9186932
TI  - A primary health care approach to an outbreak of cutaneous larva migrans.

PMID- 9186934
TI  - The effect of treatment with a slow-releasing oxytocin preparation at the onset
      of oestrus on the ovulation rate of Merino ewes.
AB  - The effect of a slow-releasing oxytocin preparation on the ovulation rate of
      Merino ewes was investigated. Synchronised Merino ewes were subcutaneously
      injected with a slow-releasing preparation containing 10 IU oxytocin, 48 hours
      after sponge withdrawal. Laparoscopic examination of the ovaries of all ewes was
      performed 10 d after the oxytocin treatment in order to determine the number of
      corpora lutea per ewe. The ovulation rate of the adult ewes of the treated and
      control groups was 179.1% and 159.1% respectively (p < 0.05) while that of the 2
      tooth ewes was 108.3% and 112.8% respectively (p > 0.05). It would appear that a
      higher ovulation rate can be obtained by a single injection of a slow-releasing
      oxytocin preparation at the onset of oestrus. The lack of response in the 2-tooth
      ewes was probably due to their relatively low body weight.

PMID- 9186935
TI  - Kalanchoe lanceolata poisoning in Brahman cattle in Zimbabwe: the first field
      outbreak.
AB  - Field outbreaks of Kalanchoe lanceolata poisoning in cattle on a commercial farm
      in Zimbabwe are reported. The clinical signs and pathological lesions observed in
      field cases resembled those reproduced in an experimental cow and were consistent
      with acute cardiac glycoside poisoning.

PMID- 9186936
TI  - The pathophysiology and medical management of canine osteoarthritis.
AB  - Osteoarthritis or degenerative joint disease is a condition characterised by
      degeneration of articular cartilage often associated with the formation of new
      bone at joint surfaces on margins. Commonly encountered in dogs, osteoarthritis
      may have a gradual onset, but may also occur acutely. Osteoarthritis can be a
      primary disease of joint cartilage, but is more after secondary to abnormal
      stresses on joints. This article describes the pathogenesis and progression of
      cartilage degeneration as well as the dietary, lifestyle and pharmacological
      management of osteoarthritis. Recent pharmacological developments allow the
      clinician not only to control clinical signs of the disease, but also to slow the
      progression of cartilage degeneration.

PMID- 9186937
TI  - Application of an immunoperoxidase monolayer assay for the detection of arboviral
      antibodies.
AB  - An immunoperoxidase monolayer assay (IPMA) was adapted for the detection of
      antibodies to six arboviruses: three viruses within the flavivirus group (dengue
      2, West Nile (WN) and yellow fever) and three in the phlebovirus group (Rift
      Valley fever (RVF), sandfly fever Naples and sandfly fever Sicilian). Antibody
      titers of homologous hyper-immune mouse ascitic fluid (HMAF) measured by IPMA
      were two to eight-fold less than those determined by ELISA. In tests with
      heterologous HMAF, cross-reactions frequently observed in ELISA, particularly in
      the flavivirus group, were absent in all IPMA titrations. With human serum
      samples tested for antibodies to RVF (n = 52) and WN (n = 90), the sensitivity of
      IPMA as compared with ELISA was 96 and 91%, respectively, specificity of IPMA was
      100%. In addition, the IPMA format has several advantages that make it a useful
      alternative to ELISA for diagnosing arboviral infections under field conditions.

PMID- 9186938
TI  - Construction of a cell-based high-flux assay for the rev protein of HIV-1.
AB  - The Rev of HIV-1 is essential for the replication of the viruses and is therefore
      a very attractive target for the development of antiviral drugs. To establish a
      cell-based high-flux assay system for random screening of Rev inhibitors, cells
      carrying both the Rev-expressing gene and a Rev-inducible SeAP gene were
      generated by permanent transfection. SeAP produced by these cells was 5-10-fold
      higher than that synthesized by cells not carrying the Rev gene. Northern blot
      analysis demonstrated that the increase in SeAP was due mainly to an increase in
      SeAP transcripts, indicating the effect of Rev proteins synthesized by the
      transfected cells. The assay system reported in this study should be useful for
      screening novel Rev inhibitors.

PMID- 9186939
TI  - Molecular characterization of avian reoviruses using nested PCR and nucleotide
      sequence analysis.
AB  - A nested polymerase chain reaction (PCR) with subsequent nucleotide sequence
      analysis identified and differentiated avian reoviruses (ARVs). PCR products
      amplified from the S1 gene segment of ARV of USA isolates were 738 and 342 bp,
      respectively. PCR products were conformed by Southern and dot blot
      hybridizations. The amplified cDNA fragments were cloned into the pUC18 vector
      and subjected to DNA sequencing. The nucleotide and deduced amino acid sequences
      of four USA (S1133, 1733, 2408, and CO8) and two Australian isolates (RAM-1 and
      SOM-4) were compared. Results of paired difference analysis and a predicted
      dendrogram revealed that USA isolates were closely related, but different from,
      Australian isolates. The deduced amino acid sequences of the N-terminal region of
      ARV sigma C showed a heptapeptide repeat of hydrophobic residues in all ARV
      isolates.

PMID- 9186940
TI  - An indirect ELISA for the detection of antibodies against porcine reproductive
      and respiratory syndrome virus using recombinant nucleocapsid protein as antigen.
AB  - An indirect enzyme-linked immunosorbent assay termed rnPRRS ELISA using
      baculovirus-expressed and affinity-purified viral nucleocapsid protein (rNC)
      antigen was developed for detecting antibodies against porcine reproductive and
      respiratory syndrome virus (PRRSV) in swine sera. Sera (1395) originating from
      different European countries were used for the validation of this assay. The
      rnPRRS ELISA was capable of detecting antibodies in all sera known to contain
      anti-PRRSV antibodies, resulting in 100% sensitivity. The specificity was 95.8%.
      The rnPRRS ELISA was more sensitive compared to the most widely used tests for
      the diagnosis of porcine reproductive and respiratory syndrome (PRRS) (i) a
      commercially available ELISA; (ii) the indirect immunofluorescence assay (IIFA);
      and (iii) the immunoperoxidase monolayer assay (IPMA). The main advantage of the
      rnPRRS ELISA compared to an ELISA using whole virus antigen is the use of a
      single immunogenic protein instead of infectious PRRSV. The rnPRRS ELISA is
      suitable for routine diagnosis of PRRS and also for epidemiological surveys since
      it allows highly reliable testing of a large number of sera within a short period
      of time.

PMID- 9186941
TI  - Specific inhibition of delta antigen by in vitro system by antisense
      oligodeoxynucleotide: implications for translation mechanism and treatment.
AB  - Synthetic antisense oligodeoxynucleotides (ODNs) and a system containing
      transcription and translation coupled rabbit reticulocyte lysate were used to
      develop a new model modulating the synthesis of small delta antigen which, in
      turn, inhibits the replication of HDV (hepatitis D virus). The ODN was stable for
      at least 50 min in this system at 37 degrees C. Unmodified 15-mer antisense D3
      and D4, complementary to translation initiation region and coding region,
      respectively, inhibit the synthesis of small delta antigen by 95% at a
      concentration of 5 microM, whereas antisenses complementary to 5' noncoding
      region, stop codon region and polyadenylation site were less effective. This
      system also showed a dose-dependent inhibitory effect of antisense D3 on the
      production of the target protein. However, the synthesis of E6 protein, an
      internal control, was not affected. These observations imply that this in vitro
      system is convenient for rapid screening of effective antisense compounds and
      offers a promising perspective for the investigation of translation mechanisms
      and for the inhibition of HDV replication by antisense strategy.

PMID- 9186942
TI  - Amplification and cloning of complete enterovirus genomes by long distance PCR.
AB  - A method for amplification and cloning of complete enterovirus cDNA genomes is
      described. Viral RNA was reverse transcribed using an optimized protocol and a
      reverse transcriptase with reduced RNase H activity. Amplicons corresponding to
      complete genomes of 14 prototype strains of group B coxsackieviruses and
      echoviruses were amplified using oligonucleotide primers derived from the
      Coxsackievirus B3 genomic sequence of the 5' and 3' ends and a mixture of
      thermostable DNA polymerases. Coxsackievirus B2 amplicon was then cloned and the
      terminal sequences of the insert were determined. Lipofection of individual
      clones resulted in productive. Coxsackievirus B2 infection. The method described
      makes it possible to obtain large amounts of complete enterovirus cDNAs and
      simplifies the construction of infectious full-length cDNA clones. Successful
      amplification of all enterovirus prototype strains tested emphasizes the general
      use of the method described, which provides a rapid and efficient alternative to
      traditional cloning strategies.

PMID- 9186943
TI  - Construction of hepatitis C-SIN virus recombinants with replicative dependency on
      hepatitis C virus serine protease activity.
AB  - An in vivo assay system was developed for the serine protease of hepatitis C
      virus (HCV) using the sindbis (SIN) viral replication system in which HCV serine
      protease activity is essential for the replication of the HCV-SIN chimeric virus.
      Two chimeric viral cDNA clones were constructed by inserting the NS3/4A region
      and NS3/4A region with the putative helicase deleted, into the N-terminal region
      of SIN core protein. The constructs were named Tpro CT and Tpro T, respectively.
      BHK-21 cells transfected with the in vitro transcribed RNAs from Tpro CT and Tpro
      T showed specific cytopathic morphology and produced chimeric viruses, Vpro CT
      and Vpro T. In contrast, in vitro transcribed RNAs from Tpro CTI and Tpro TI, in
      which serine of catalytic triad of HCV protease was changed to alanine, were not
      infectious. When the chimeric viruses were passaged in BHK-21 cells at about 0.1
      multiplicity of infection (MOI), Vpro T, but not Vpro CT, stably expressed HCV
      protease for up to five passages. Surprisingly, the cell culture media of BHK-21
      cells infected with Vpro T, compared to wild-type sindbis virus, showed rapid pH
      changes by more than 0.8 pH degree at 72 h post-infection. HCV-SIN hybrid viruses
      could be used in screening the HCV protease-inhibitor in cell culture systems.

PMID- 9186944
TI  - CD4 deletion mutants evaluated for human immunodeficiency virus type 1
      infectivity in a highly efficient system of expression and detection based on LTR
      dependent reporter gene activation.
AB  - The human CD4 glycoprotein is thought to be involved at several stages of the
      infection process with the human immunodeficiency virus type 1. To pursue this
      line of investigation with CD4 deletion mutants, we combined a system of high
      transient cell-surface expression of the target molecule with an assay of HIV-1
      infectivity based on induction of LTR-linked luciferase activity. The approach
      was also designed to distinguish between defects in gp120 binding and postbinding
      events. Optimal assay conditions were established with wild-type CD4 and the
      previously characterized CD4 mutant, d367-371. New deletions of CD4 domains D3
      and D4 were then designed from a rat model of the D3D4 atomic coordinates with
      the concern of maintaining overall structural integrity. While all CD4 mutants
      were found to be defective towards HIV, it was demonstrated that the mutations
      affected different stages of the entry process. These data indicate that the
      system is well suited for studying the intricacy of molecular interactions
      involving HIV envelope glycoproteins and its receptors.

PMID- 9186945
TI  - Quantitative assessment of hepatitis C virus RNA by polymerase chain reaction and
      a digoxigenin detection system: comparison with branched DNA assay.
AB  - A method for quantifying hepatitis C virus (HCV) RNA in serum using reverse
      transcription-polymerase chain reaction (RT-PCR) followed by slot-blot
      hybridization with a specific, digoxigenin-labeled probe was developed. Using RNA
      synthesized from cloned HCV cDNA as a standard, serum concentration of HCV RNA
      above 10 copies/ml can be quantitatively determined. To compare this method with
      branched DNA (bDNA) assay, 45 serum samples from 26 patients with newly acquired
      acute hepatitis C (n = 16) or hepatitis C with acute exacerbation (n = 10) were
      submitted to both assays. HCV RNA in 30 (67%), 12 (27%) and three (6.7%) samples
      can be quantitatively determined by both, either and none of the two assays,
      respectively. Using a standardized qualitative HCV RNA detection test (Amplicor
      HCV test) as a reference, 1 and 0 false positive results were found by bDNA and
      this assay, respectively. This quantitative assay using RT-PCR and a digoxigenin
      detection system was comparable to bDNA assay. Since a false positive result was
      rarely found, this technique can be used as a first line test to screen a large
      number of samples rapidly and economically.

PMID- 9186946
TI  - Detection of lactate dehydrogenase-elevating virus in transplantable mouse tumors
      by biological assay and RT-PCR assays and its removal from the tumor cell.
AB  - It is known that lactate dehydrogenase-elevating virus (LDV) of mice is a common
      contaminant of transplantable tumors of both murine and human origin. It is
      imperative that tumors that are maintained by transplantation in mice are
      examined for LDV and freed of the virus, when present, before use in experimental
      studies, because an LDV infection of mice exerts considerable effects on lymphoid
      cell populations and cytokine production and other effects. Methods for LDV
      detection are described using a biological assay and reverse transcription (RT)
      polymerase chain reaction (PCR) technology and their application is illustrated.
      A differential RT-PCR method that distinguishes between three quasispecies of LDV
      is also described and applied to an examination of LDVs isolated from a number of
      different tumors. Each of the LDV isolates was found to contain at least two
      different quasispecies, generally in different concentrations.

PMID- 9186947
TI  - Direct blotting electrophoresis for sequencing and genotyping hepatitis C virus.
AB  - Many methods have been used to differentiate the hepatitis C virus (HCV)
      genotypes based on, for example, type specific primers, probes and restriction
      fragment length polymorphism. However, determination of the nucleotide sequence
      remains the reference. Therefore, a simple non-radioactive cycle sequencing
      technique was developed for clinical tests. PCR-amplified products of the 5' non
      coding region (from position -274 to -31) were sequenced using a 5' digoxygenin
      labeled primer. After denaturation, the samples were loaded on a direct blotting
      electrophoresis system (GATC 1500). Sequencing products were blotted onto a nylon
      membrane during the electrophoresis. The DNA fragments were then UV-cross-linked,
      incubated with phosphatase-labeled anti-digoxygenin antibody and stained with a
      precipitating substrate. Reading the sequence of six samples were possible within
      2 days. In 41 different samples, five different genotypes were found by sequence
      analysis from position -245 to -69, of which 17 were type 1a, 7 type 1b, 5 type
      2a, 8 type 3a, 3 type 4 and 1 type 5. These results agreed with those obtained by
      reverse hybridization assay. Direct blotting electrophoresis offered a good non
      radioactive method of performing clinical sequencing on a medium scale, with a
      minimum of investment.

PMID- 9186948
TI  - What technique should be used for routine detection and quantification of HBV DNA
      in clinical samples?
AB  - Detection of hepatitis B virus (HBV) DNA in serum allows monitoring of HBV
      replication and assessing responses to antiviral treatment. HBV DNA
      quantification measures virus replication and can be used as a prognosis
      indicator of liver disease and an index of response to antiviral drugs. The aim
      of this study was to compare the performances of three HBV DNA detection and/or
      quantification techniques for assessing HBV replication. Three hundred unselected
      sera with a request for HBV DNA detection and quantification were tested with a
      molecular hybridisation technique without amplification (Digene Hybrid-Capture,
      Murex Diagnostics Ltd), a signal amplification assay based on branched DNA
      technology (Quantiplex HBV DNA, Chiron diagnostics), and an 'in-house'
      qualitative, non quantitative target amplification assay based on the polymerase
      chain reaction (PCR) with primers located in the S gene of the HBV genome. Hybrid
      capture and branched DNA gave concordant results in 278 cases (93%). In the 128
      samples positive by both assays, DNA titres in pg/ml were related significantly
      (r = 0.70, P < 0.0001). but branched DNA titres increased more rapidly than
      hybrid-capture titres when the amount of HBV DNA in the sample increased. Twenty
      two sera (7%) were negative by hybrid-capture, but positive in branched DNA
      (detection rate gain: 15%). In these 22 patients, DNA titres were low, HBsAg was
      present in all instances and alanine aminotransferase activity was elevated in 18
      patients (82%); HBeAg was present in seven patients (32%) and anti-HBe antibodies
      in 18 patients (82%); liver biopsy, undertaken in 18 patients, revealed chronic
      active hepatitis in all instances, associated with cirrhosis in eight cases.
      Qualitative, non-quantitative HBV DNA PCR was positive in 75 (50%) of the 150
      hybrid-capture-negative, branched DNA-negative samples, including a significant
      proportion of patients without evidence of ongoing HBV-related liver disease. The
      results show that in general, the branched DNA assay detects HBV DNA in more
      patients than hybrid-capture and that this improved detection rate is relevant
      clinically and genome equivalents/ml are preferred to pg/ml to quantify HBV DNA
      in clinical specimens and finally qualitative, non-quantitative polymerase chain
      reaction can detect HBV DNA in patients without evidence of active HBV-related
      liver disease. This study emphasizes the need for more sensitive, university
      standardised quantitative HBV DNA assays and for the definition of clinically
      relevant cutoffs with these assays.

PMID- 9186949
TI  - Expression of the nonstructural protein NS1 of equine influenza A virus:
      detection of anti-NS1 antibody in post infection equine sera.
AB  - The nucleotide sequence of the nonstructural protein NS1 of the influenza virus
      A/equine 2/Suffolk/89 was determined and found to be 97% identical to that of
      A/equine 2/Miami/63. A similar level of identity was shown for the deduced NS1
      amino acid sequence. The NS1 gene was expressed, in its entirety and in part, as
      fusion proteins with glutathione S-transferase using the pGEX-3X expression
      vector. Antibodies to NS1 protein were detected in serum samples from ponies
      experimentally infected with influenza virus, but not in animals vaccinated with
      whole inactivated virus or in unprimed control animals. The antigenic
      determinant(s) of NS1 protein appear to be located in the C-terminal half of the
      protein. The implications of these findings are discussed with reference to the
      use of NS1 protein as a differential diagnostic marker for influenza virus
      infection in the presence of high levels of circulating antibody to influenza
      haemagglutinin generated by recent vaccination.

PMID- 9186950
TI  - Enterovirus genomes in wastewater: concentration on glass wool and glass powder
      and detection by RT-PCR.
AB  - Standard methods for detecting enteroviruses in environmental samples require
      cell culture, which is time consuming and expensive. The reverse transcription
      polymerase chain reaction (RT-PCR) is a rapid, sensitive method for detecting
      enteroviruses in water. However, environmental samples often contain substances
      that inhibit PCR amplification of target RNA. Hence the virus must be
      concentrated by procedures that do not interfere with amplification. This study
      shows that virus concentration by adsorption onto glass powder or glass wool
      supports is suitable for detecting viral genomes in treated wastewater by RT semi
      nested PCR. No enterovirus genome was detected directly in 25 samples of treated
      wastewater by RT semi-nested PCR. However, samples concentrated by adsorption
      onto glass wool or glass powder showed that 48% (glass powder) and 56% (glass
      wool) contained virus. Secondary concentration by organic flocculation was
      unsuitable for detecting virus concentrated on glass wool (20% positive samples),
      but it helped to increase the detection of the genome after concentration on
      glass powder (72% positive samples).

PMID- 9186951
TI  - Detection of the infectious hematopoietic necrosis virus directly from infected
      fish tissues by dot blot hybridization with a non-radioactive probe.
AB  - A method was developed for the rapid diagnosis of the infectious hematopoietic
      necrosis virus (IHNV) based on dot blot hybridization with a non-radioactive
      probe. When the assay was developed through a color reaction both biotin- and
      alkaline phosphatase-labeled probes were highly specific for IHNV and the
      sensitivity reached to 20 pg of viral RNA. When the alkaline phosphatase-labeled
      probe was developed by a chemiluminiscent reaction, the sensitivity showed a five
      fold increase to 4 pg of viral RNA. The procedures successfully detected IHNV
      directly from infected symptomatic and asymptomatic fishes exhibiting higher
      sensitivity than the traditional approaches involving viral propagation in cell
      cultures. Additional advantages of the method are its simplicity and it takes
      only about 6 h to carry out the procedures from the initial processing of the
      tissues to diagnosis.

PMID- 9186952
TI  - Elution and reconcentration of coliphages in water from positively charged
      membrane filters with urea-arginine phosphate buffer.
AB  - Coliphages in drinking water and waste water samples have been adsorbed onto
      positively charged membrane filters, eluted with urea-arginine phosphate buffer
      (UAPB), reconcentrated, and detected with Escherichia coli C (ATCC 13706). The
      proposed membrane filter-based UAPB method for concentration and detection of
      coliphages compares favorably with the beef extract elution and reconcentration
      procedure and also with the proposed coliphage detection procedure described in
      Standard Methods for the Examination of Water and Wastewater. The higher recovery
      of coliphages with UAPB elution from positively charged membrane filters is
      attributed to testing the whole volume of concentrated sample, rather than
      partial analysis of the sample as in the procedure described in Standard Methods
      for the Examination of Water and Wastewater, especially when the titre is very
      low.

PMID- 9186953
TI  - Demonstration of human papillomavirus (HPV) genomic amplification and viral-like
      particles from CaSki cell line in SCID mice.
AB  - We demonstrate that from the CaSki cervical cancer cell line, integrated HPV-16
      genome was amplified and viral-like particles were generated in an in vivo SCID
      mouse model. The in vivo tumor growth of several HPV-containing cell lines and 2
      HPV-negative cell lines was examined in SCID mice. Tumor growth was noted with
      the HeLa, CaSki, ME-180, and MS751 cell lines within 2 months after subcutaneous
      injection. Squamous differentiation was appreciated in focal areas of tumors
      derived from CaSki and ME-180. In the CaSki tumors, DNA in situ hybridization
      revealed homogeneous staining of nuclei in some cells in the differentiated
      areas, suggesting HPV genomic amplification. In contrast, punctate or speckled
      patterns of hybridization were identified in the less differentiated areas,
      suggesting continued integration of the HPV genome. Immunocytochemical staining
      for HPV-16 L1 capsid protein showed it to be concentrated in cells from the
      differentiated areas, correlating with the results of hybridization. Electron
      microscopic studies revealed 50 nm uniform particles, consistent with HPV viral
      like particles, in the nuclei of some cells in well-differentiated areas.
      Furthermore, Southern transfer and hybridization of the Hirt's extract from the
      CaSki tumors was positive for HPV-16 DNA, indicating non-integrated, low
      molecular weight HPV-16 DNA. Our results show HPV genomic amplification of
      integrated viral DNA and generation of HPV viral-like particles in CaSki cancer
      cells in SCID mice and that viral DNA amplification and the formation of viral
      like particles are coupled to cellular differentiation. This experimental model
      provides a potential system for studying the molecular pathogenesis of HPV
      infections.

PMID- 9186954
TI  - New quantitative assay of hepatitis B and C viruses by competitive PCR using
      alternative internal sequences.
AB  - A competitive PCR was developed for quantitation of hepatitis B virus (HBV) DNA
      and hepatitis C virus (HCV) RNA, alternatively, using only two constructions
      containing both priming sites. DNAs corresponding to the HBV-S gene and the HCV
      5' non-coding region were introduced into distinct plasmids. HBV plasmid was used
      as a standard for HBV-DNA quantitation, in competition with the HCV plasmid as
      internal control. HBV and HCV plasmids also served as template for transcription
      of HBV-RNA, and HCV-RNA, which was used as internal control and standard,
      respectively, in competition for HCV-RNA quantitation. The analyzed samples for
      HBV and HCV quantitation were processed in the same way in competition with the
      internal controls and to the respective calibration curves obtained by serial
      dilutions of the mimic standard. This method showed very good specificity and
      sensitivity, allowing absolute quantitation in a large linear range from 5 viral
      genomic copies per assay up to 10(6) copies, in sera of chronically HBV and HCV
      infected patients, as well as in supernatants of cell cultures inoculated with
      these viruses.

PMID- 9186955
TI  - A DNA hybridization method for typing hepatitis C virus genotype 2c.
AB  - A high prevalence of hepatitis C virus (HCV) genotype 2c (22%) was detected in
      sera from 459 italian patients by core-region amplification and hybridization
      with specific probes by DNA enzyme immunoassay. Amplified fragments failed to
      hybridize with 1a, 1b, 2a, 2b and 3a subtype-specific and 4, 5, 6 type-specific
      oligonucleotides in 105 patients. Hybridization of these samples with type 2
      probe, which recognized all the subtypes sequences, showed evidence for genotype
      2 distinct from 2a and 2b. Fourteen out of these 105 isolates were cloned and
      sequenced. The results were consistent with genotyping assay. Nucleotide
      sequences were partially related to types 2a, 2b, 2d, 2e and 2f (87.0-93.5% of
      identity). The average nucleotide identity was highest for genotype 2c (95.87%).
      On the basis of sequence analysis, subtype 2c specific probe was derived.
      Hybridization efficiency with the newly designed probe was very high and more
      than 95% (100/105) of type 2 cases were classified as 2c. Evidence of different
      outcome of therapy inside the same HCV major type account for the need of
      accurate subtyping. In this study, amplification of the core region followed by
      hybridization with highly specific probes enabled distinction between HCV
      subtypes.

PMID- 9186957
TI  - Negotiating relevance: belief, knowledge, and practice in international health
      projects.

PMID- 9186958
TI  - Studying knowledge, culture, and behavior in applied medical anthropology.
AB  - In this article we argue that the concept of knowledge, as utilized by public
      health professionals, is best regarded as cultural belief, as defined in
      anthropology. The implications of this position are explored, particularly as it
      relates to the development of a decision-making approach to the understanding and
      analysis of health care behavior. The methodological challenges posed by the new
      theoretical perspective that has emerged from the emphasis on decision making is
      discussed from the perspective of applied research. The role of focused
      ethnographic studies is examined and contrasted with ethnomedicine and survey
      approaches. Some main features of focused ethnographic methods are described and
      illustrated with a case example of acute respiratory infection (ARI) in Gambia.

PMID- 9186959
TI  - Television minidramas: social marketing and evaluation in Egypt.
AB  - Television has been extensively used to communicate health messages for over a
      decade in Egypt. Viewers of the evening soap operas have been seeing six
      commercials for family planning, oral rehydration solution (ORS), and
      immunizations. People of all social classes can sing the jingles of the most
      popular ads. The producers of these health spots use increasingly sophisticated
      story lines, settings, and characters representing rural peasants, played by
      popular and well-liked actors. Evaluation of the content and impact of these
      messages has lagged behind the creative sophistication of their production. This
      article reviews the context and content of televised health messages in Egypt
      during the 1980s, critically assesses the evaluation of mass media health
      education, and suggests strategies for more effective evaluation. The author
      worked for some years with a private donor agency that funded the production of a
      number of televised health commercials in Egypt.

PMID- 9186961
TI  - The ethnoecology of dengue fever.
AB  - This article employs an ethnoecological analysis to link indigenous,
      ethnomedical, and Western biomedical ideas of infectious disease
      causation/prevention. The ethnoecological analysis is expanded to include the
      cultural and historical context of political will and community participation in
      dengue fever control activities in an urban neighborhood in the Dominican
      Republic. Findings indicate that a key source of dengue fever transmission has
      been overlooked because it falls between established gender-role boundaries, and
      that mala union, an explanatory concept central to the failure of previous
      community-based interventions, emerges from local views of national political
      history. Data were generated through a neighborhood household survey, key
      respondent interviews, and participant-observation.

PMID- 9186960
TI  - Sociocultural aspects of tuberculosis control in Ethiopia.
AB  - This article examines ethnomedical knowledge and practices related to
      tuberculosis conceptualization and management in a rural southern Ethiopian
      community. An adult health-status survey, administered to 217 adults selected
      through quota sampling procedures, investigated prevailing nosological
      structures. Additionally, disease-enhancing behaviors were identified through
      qualitative-research methods. The findings show that while symptomatological
      concepts coincide with biomedicine, the local etiological model postulates
      empirically based causational factors unrelated to tubercle bacilli. Therapeutic
      preference hinges on the utilization of ethnobotanical remedies and their
      expected emetic effects. The relevance of tuberculosis-related ethnomedical
      knowledge and management practices is discussed in relation to primary health
      care and disease-control programs in Ethiopia. It is recommended that health
      education interventions, illustrating the nature and transmission avenues of
      tuberculosis and the effects of biomedical therapies, precede and/or accompany
      vaccination campaigns or chemotherapy. Teaching materials should valorize
      existing ethnomedical notions that emphasize contagion as an avenue of disease
      transmission, and the importance of nutritional adequacy in fighting the disease.

PMID- 9186962
TI  - Predicting treatment-seeking behavior in Guatemala: a comparison of the health
      services research and decision-theoretic approaches.
AB  - This study attempts to identify and describe factors associated with the choice
      of a health care source in rural Guatemala. Because of limited choice options,
      rural Guatemala makes an excellent location for studying the factors that affect
      utilization patterns. Illness case histories were collected from a random sample
      of 270 households in six villages. Then, two different methodological approaches
      were used to predict treatment actions. First, a sociobehavioral model, which
      encompasses enabling, predisposing, and need factors, was used to predict
      treatment choices. Using discriminant analysis we identified factors associated
      with the use of home remedies, a pharmacy, the health post, a physician, or folk
      healer. In a second, parallel study, descriptive interviews were used to identify
      important factors in choosing a treatment strategy. From these interviews, and
      from responses to hypothetical illness cases, we developed a decision model of
      treatment actions. Both models were tested against the set of illness cases.
      Results indicate that both approaches identify similar variables (especially,
      severity), although selection of variables through the multivariate analysis was
      much more successful in predicting treatment actions.

PMID- 9186963
TI  - At work in the fields of public health: the abuse of rationality.

PMID- 9186964
TI  - More thoughts on negotiating relevance.

PMID- 9186965
TI  - Glycerol administration modulates the pattern of the 3-fucosyl-N-acetyl
      lactosamine (CD15) epitope in the adult guinea pig inner ear.
AB  - The effect of glycerol administration on the distribution pattern of the CD15 (3
      fucosyl-N-acetyl-lactosamine) epitope has been studied immunohistochemically in
      hydropic and non-hydropic ears of adult guinea pigs from 80 min to 5 h after
      treatment with 2 g/kg glycerol. Glycerol administration characteristically
      modulated the immunoreactivity of the CD15 epitope in the endolymphatic sac and
      the tectorial membrane (TM) and revealed the CD15 epitope in the otoconia of the
      saccule, the stereocilia and the supporting cells of the ampullae. Our results
      suggest that glycerol interacts with glycoconjugates of the TM and otoconia,
      causing changes in their density and possibly the hydration state. As a
      consequence, the transduction process may be affected.

PMID- 9186966
TI  - Ultrastructural localization of glutamate and aspartate immunoreactivities in
      gerbil inner hair cells.
AB  - The endogenous neurotransmitter released at the base of cochlear inner hair cells
      (IHCs) is still not clear. L-Glutamate is the most likely candidate at present.
      Although it has been demonstrated that IHCs contain high levels of glutamate, the
      association of glutamate with synaptic release has not yet been established. In
      this study, presynaptic location of glutamate and aspartate immunoreactivities
      was examined by using the postembedding immunogold technique. The results show
      that neither glutamate nor aspartate exhibit immunoreactivities around the
      synaptic vesicles of IHCs. Although the results do not support the hypothesis
      that glutamate or aspartate is the endogenous neurotransmitter, the possibility
      that the real transmitter is a substance with a structure very similar to
      glutamate or aspartate cannot be excluded.

PMID- 9186967
TI  - Longitudinal non-invasive perilymphatic pressure measurement in patients with
      Meniere's disease.
AB  - The homeostasis of inner-ear fluids is essential for the functions of hearing and
      equilibrium. Inner-ear disorders, such as Meniere's disease, are affected by
      inner-ear pressure. The displacement of the human tympanic membrane can be
      studied by means of the MMS-10 Tympanic Displacement Analyser (Marchbanks
      Measurement Systems Ltd., UK) and is thought to be a measure for perilymphatic
      pressure variations. This measurement was performed in 18 patients with Meniere's
      disease (20 affected ears) at regular intervals, in order to investigate possible
      pressure variations in relation to the following symptoms: hearing loss, vertigo,
      tinnitus and pressure sensation. Symptoms changed independently; changes in
      symptoms were not significantly related to changes in perilymphatic pressure, as
      measured by means of the MMS-10 analyser.

PMID- 9186968
TI  - The influence of aging on auditory brainstem response and electrocochleography in
      the elderly.
AB  - Auditory brainstem responses and simultaneous transtympanic
      electrocochleographies were investigated in 92 subjects aged between 50 and 89
      years with normal hearing or mild presbycusis. Subjects were classified into four
      age-related groups: 16 subjects in the sixth decade, 28 in the seventh decade, 32
      in the eighth decade and 16 in the ninth decade. Thirty young subjects with
      normal hearing aged 20-29 years were chosen as controls. The result showed
      progressive delay of wave I (or action potential: AP), wave III and wave V and
      lengthening of the interpeak intervals (IPIs) of waves III-V and I-V in the
      subjects aged 50-79 years. In the subjects in the ninth decade, shortening of
      IPIs of waves I-III and I-V was noted in spite of further delays of wave I. The
      amplitude of APs on electrocochleography decreased in the groups with mild
      presbycusis. Both the lengthening and shortening of IPIs might be
      electrophysiological alterations occurring with aging in the central auditory
      pathways.

PMID- 9186969
TI  - Etretinate-induced malformation of the first two branchial arches: differential
      staining and microdissection study of embryonic cartilage.
AB  - Malformations of the cranial base, temporal bone and middle ear were induced in
      the offspring of Sprague-Dawley rats by a single intraperitoneal injection of 10
      30 mg/kg etretinate (Tigasone) at days 8.5-10.5 of gestation. By differential
      staining of the embryonic craniofacial cartilage and bone, and microdissection of
      the otomandibular complex, the induced malformations were studied specifically.
      Defective formations of Meckel's cartilage and the cartilaginous skull base were
      found to be prominent features of the malformation. The malformation included
      defective middle-ear ossicles; especially the malleus and incus were fused with a
      shorter than normal long process and manubrium. In conjunction with the distal
      part of Meckel's cartilage, mandibular micrognathia was observed. All of the
      malformed tissues are derivatives of the first and second branchial arches. The
      teratogenically induced defects in the rat embryos show some similarities to the
      clinical syndromes of the first and second branchial arches in man.

PMID- 9186970
TI  - Comparison of effectiveness of maneuvers and medication in the treatment of
      benign paroxysmal positional vertigo.
AB  - In this paper, the treatment by medication together with two maneuvers-the
      particle repositioning maneuver (PRM) reported by Parnes and Price-Jones and the
      liberatory maneuver (LM) reported by Semont et al.-were compared with treatment
      by medication alone. Fourteen of 15 cases (93.3%) treated with the PRM and 11 of
      14 cases (78.6%) treated with the LM showed improvement after 2 weeks. These
      results were better than that obtained by medication alone, in which 8 of 26
      cases (30.8%) showed improvement after 2 weeks. The most important benefit of
      these maneuvers seemed to be the speedier recovery than with medication alone, as
      there was no significant difference in the late success rate after 3 months
      between the maneuvers and medication alone.

PMID- 9186971
TI  - Electromyographic analysis of profound facial nerve paralysis following acoustic
      neuroma resection.
AB  - The aim of our retrospective study was to determine whether electromyographic
      findings (motor unit action potentials, MUAPs) can be used in long-term prognosis
      for profound facial nerve paralysis in patients whose nerve continuity is
      preserved during surgery for acoustic neuroma. The orbicularis oris, frontal, and
      orbicularis oculi muscles were examined for the occurrence of MUAPs in 48 such
      patients. In 30 patients who recovered from complete paralysis within 10 months
      after surgery, MUAPs in the first two muscles tended to precede the first sign of
      facial movement. MUAPs appeared in the orbicularis muscle in 80% of these
      patients at 1 month and in all at 5 months. In the frontal and orbicularis oculi
      muscles, MUAPs occurred in only 0-20% of these patients in the first month;
      within 3-5 months the number increased rapidly, and MUAPs were present in 95% of
      these patients at 10 months. In the remaining 18 patients with long-term complete
      paralysis (at least 1 year), MUAPs appeared solely in the orbicularis oris
      muscle: in 20% of these patients in the first month after surgery. While this
      number slowly rose, there was no period of rapid increase later. We conclude that
      the occurrence of MUAPs in the orbicularis oris and frontal muscles within 3
      months of surgery indicates a good prognosis for reversal of facial nerve
      paralysis.

PMID- 9186972
TI  - Morphological distribution of middle-ear epithelium in the Wistar rat: a
      functional hypothesis.
AB  - The authors studied the overall microscopical anatomy of the middle ear and of
      the eustachian tube in 20 tympanic bullae of 10 Wistar rats. Large hexagonal
      epithelial flat cells covered the roof of the bulla, the two upper thirds of both
      lateral walls, the upper half of the eustachian tube, and the upper third of the
      tympanic orifice; ciliated and secretory cells lined the inferior thirds of both
      walls of the bulla while a ciliated epithelium with strong cilia, all directed
      towards the tubal orifice, located on the floor of the tympanic cavity together
      with groups of non-ciliated cells was detectable near the tubal and antral areas
      and on the floor of the eustachian tube. Non-ciliated cells covered by microvilli
      were found near the pharyngeal orifice. These observations seem to demonstrate
      the following: (1) the ciliated elements present a well-defined topographic
      distribution; (2) a preferential pathway for mucociliary clearance made up of
      strong ciliated cells located on the floor of the bulla is clearly detectable,
      and (3) the roof of the bulla seems to be mainly involved in the ventilatory
      function.

PMID- 9186974
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi's disease) of the cervical lymph
      nodes.
AB  - Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi's disease, is a benign
      cause of lymph node enlargement of unknown origin. It may be mistaken for
      malignant lymphoma, both clinically and histologically. Though well recognized in
      the pathological literature few clinicians are aware of the disease. We present a
      case of cervical HNL and review the literature.

PMID- 9186973
TI  - Extracellular ATP modulates ion transport via P2Y purinoceptors in a middle-ear
      epithelial cell line.
AB  - Mucus and cellular debris are eliminated from the middle-ear cavity through the E
      tube by the mucociliary system. Depth of the periciliary fluid layer is thought
      to be regulated by epithelial ion transport activity. Since impairment of the
      mucociliary system is a key step in the development of otitis media with
      effusion, we investigated the ion transport mechanisms of the middle-ear
      epithelium using the middle-ear MESV cell line. ATP has been shown to modulate
      ion transport as well as various cellular functions in several cell types via
      purinoceptors. In order to investigate a possible modulation of the transport
      activity of MESV cells, we evaluated short-circuit current (Isc) changes in
      response to specific stimulation of putative purinoceptors by ATP and its various
      analogs. ATP dramatically increased Isc, while adenosine had no effect, thus
      demonstrating the presence of P2 receptors according to the original
      classification by Burnstock. The rank order of potency of purinoceptor agonists
      for stimulation of Isc on the apical side (ATP > UTP > gamma-SATP >> beta-SADP >
      2-methylthio-ATP, 2MeSATP > beta, gamma-methylene-ATP, beta,gamma-MeATP) and on
      the basolateral side (ATP > gamma-SATP > UTP >> beta-SADP > 2 MeSATP > beta,gamma
      MeATP), along with studies using selective antagonists and intracellular calcium
      measurements are consistent with a P2Y receptor subtype. The ATP-induced increase
      in Isc was related to sodium transport. This modulation might be of importance in
      stress conditions such as inflammation.

PMID- 9186976
TI  - Laryngeal neurinoma. A case report and review.
AB  - A case of neurinoma of the larynx is presented. Pathological, clinical,
      diagnostic and therapeutic findings are discussed and the relevant literature is
      reviewed.

PMID- 9186975
TI  - Glomangioma of the nasal cavity. Case report and literature review.
AB  - A case of glomangioma of the nasal cavity and the literature concerning this rare
      tumor are reported. Differential diagnosis, symptoms, pathogenesis and therapy
      are discussed. This uncommon benign neoplasm is seldom located in the upper
      respiratory tract. It originates from proliferating arteriovenous capillary
      anastomoses. Intranasal glomus tumors produce nasal obstruction, epistaxis and
      sharp pain. The treatment of choice is complete excision of the tumor. The
      prognosis is excellent when the glomangioma is completely removed.

PMID- 9186977
TI  - Personality and endogenous/major depression: an empirical approach to typus
      melancholicus. 1. Theoretical issues.
AB  - The concept of typus melancholicus (TM) was shaped by Tellenbach by means of
      phenomenological analysis in order to describe the premorbid and intermorbid
      personality of endogenous depressives. In this paper, the authors delineate the
      core properties of TM-i.e. orderliness, conscientiousness, norm orientation and
      intolerance of ambiguity-as a point of departure for empirical-statistical
      research. Qualitative and quantitative studies inquiring the characteristics of
      TM are reviewed in order to point out its well-established personality
      dimensions. Alternating methodological steps are proposed, combining
      phenomenological hypotheses with empirical-statistical tests (hermeneutic
      complementarity) in order to validate and differentiate the TM concept. The
      question whether TM should be considered as a personality disorder and the
      ethical attitude of subsiding appreciation of the TM in different generations of
      psychiatrists are discussed. It is emphasized that the TM concept brings
      otherwise unsystematized observations of depressives' intermorbid personality
      features into a coherent theoretical framework.

PMID- 9186978
TI  - Personality and endogenous/major depression: an empirical approach to typus
      melancholicus. 2. Validation of typus melancholicus core-properties by
      personality inventory scales.
AB  - The purpose of this study was to objectify some of the personality dimensions of
      the typus melancholicus (TM) personality formation in endogenous depressives and
      to compare the consistency of the term used in questionnaires with the original
      concept as delineated in our preceding paper. The prevalence of TM in endogenous
      depressive inpatients was 51% for patients with clearly salient TM features. In
      addition 25% of the sample showed TM features to a minor extent. These findings
      are consistent with the literature. MMPI and MPI could not separate TM and non
      typus melancholicus (NTM) in univariate analyses. However, the Munich Personality
      Test (MPT) contributes to validating the TM concept. TM depressives scored
      significantly higher in MPT subscales rigidity and norm orientation. According to
      its item structure the MPT rigidity subscore can be considered to conceptually
      encompass hypernomia, i.e. the patient's incapacity to change the norms that were
      once adopted. Based on the characteristics of item formulations in the MPT
      subscore norm orientation it was hypothesized that this subscore corresponds to
      the concept of heteronomia, i.e. conformism towards externally determined and
      uncritically followed social norms. Since MPT norm orientation in TM does not
      covariate with control scales of the other inventories used in this study, it is
      likely that MPT norm orientation refers to the TM patient's sincere commitment to
      social norms rather than to a sham reaction in the sense of a lie scale. There
      was no consistent indication that TM shows lower neuroticism scores than NTM.

PMID- 9186979
TI  - Perceptual grouping due to pitch and amplitude in hallucinating schizophrenics.
AB  - 17 subjects with a diagnosis of schizophrenia and hallucinations in their case
      history were compared with 16 subjects of a reference group regarding the
      appearance of a perception of streaming in a presentation of pitch alternating
      tones. One scale going up and down was used as part of a stimulus and the same
      scale going down and up as the other part (as distractor). The amplitude of the
      distractor was varied in order to make the perceptual regrouping (streaming)
      evident, which normally occurs when the amplitude approaches the same level in
      the two stimuli. Sixteen presentations were made. The subjects of the reference
      group began to hear the streaming after the sixth presentation and all of them
      heard it at the eighth. At the eleventh presentation some ceased to perceive any
      streaming and none heard it after the fourteenth presentation. In the
      schizophrenic group none showed a normal pattern. Overall, less than half of the
      schizophrenic probands heard a streaming when subjects in the reference group
      did. Amongst those who did, a few heard it early and kept hearing it to the end.
      Others started to hear it late and kept hearing it to the end, while a few heard
      it on and off. The remarkable aberrant grouping strategies among the
      schizophrenics are discussed in relation to current ideas on perceptual
      disturbances of the illness.

PMID- 9186980
TI  - The comprehension of metaphors in schizophrenia.
AB  - Metaphor comprehension was studied in schizophrenics as compared to psychiatric
      and nonpsychiatric controls. Subjects were asked in a two-condition forced-choice
      response task to detect the metaphor similar or contrary to a proverb with an
      abstract meaning. Schizophrenic patients were impaired in both conditions.
      However, the paranoid patients' performances did not differ from psychiatric and
      nonpsychiatric controls. These results are consistent with the hypothesis that
      the ability of metaphorizing is preserved in some schizophrenic patients.

PMID- 9186981
TI  - Sibship size, sibship position, parental rearing and psychopathological
      manifestations in adults: preliminary analysis.
AB  - Almost all investigations concerning the relationships between sibship size,
      sibship position and psychiatric disorders addressed more formal aspects, i.e.
      frequency and position, with contradictory and inconsistent results. Analyses
      considering sibship size and birth order as mediating factors between parental
      rearing and psychopathological manifestations in adults are lacking. The present
      results of an investigation of 1,013 psychiatric inpatients and 251 healthy
      volunteers support a systematic association between sibship size and parental
      rearing, mainly in terms of a reversed relationship between emotional warmth,
      overprotection and number of siblings. An excess of psychiatric patients in the
      middle position of a sibling seems to be related to specific unfavourable rearing
      patterns. A validation of our preliminary results would be required in terms of
      preventive measures for children of risk populations.

PMID- 9186982
TI  - Family backgrounds and eating disorders.
AB  - The aim of this study was to assess the possible relationship between the
      presence of a pathological family background and various eating disorders
      subgroups. A semi-structured interview was used to assess the socio-demographic
      and clinical characteristics and the presence of psychological complaints among
      family members of 79 subjects with anorexia nervosa (AN) and 34 subjects with
      bulimia nervosa (BN). The subjects were also administered the following self
      assessment questionnaires: BITE, EDI, and HSCL-90. There were nonsignificant
      differences between AN and BN in terms of parental mental disorders. A further
      subdivision of the patients (as indicated in DSM-IV) revealed significant
      differences in the distribution of psychiatric family history. In particular, it
      seems that the presence of purgative behavior is associated with a higher
      incidence of a pathological family background. These results suggest that
      pathological family histories are not responsible for the development of ED, but
      they are an aggravating factor both in AN and BN.

PMID- 9186983
TI  - Dissociative experiences and eating disorders in a female college sample.
AB  - The present study evaluates the relationship between abuse experiences,
      dissociation and eating disorders (ED) in an Italian female college sample. In
      particular, the study aims at comparing the dissociative effects of abuse
      experiences in ED and normal subjects. Dissociative experiences were assessed by
      Dissociation Questionnaire (DIS-Q), which appeared to be an internally consistent
      and valid instrument. The presence of ED in 491 female college students was
      assessed by a two-stage epidemiological procedure. The factor structure of the
      DIS-Q in our sample allowed us to identify specific features that could
      differentiate ED subjects from normals. Experiences of losing control appeared to
      characterize ED subjects and they were more serious in ED individuals who
      reported sexual or physical abuse. Normal subjects who reported a serious trauma
      had more frequently amnesia, identity alterations, derealization and
      depersonalization experiences when compared to nonabused subjects.

PMID- 9186984
TI  - Predictors and outcome in panic disorder: a 2-year prospective follow-up study.
AB  - 53 patients presenting at an outpatient unit for anxiety disorders were included
      in the present prospective 2-year follow-up study. Sociodemographic, illness
      history, index rating, and 2-year follow-up data were evaluated. A multiple
      stepwise regression analysis was carried out in order to find predictors of the 2
      year outcome. Results indicate that panic patients without episode at follow-up
      show less symptoms and a better psychosocial functioning than patients with
      episode at follow-up. Comorbid generalized anxiety disorder, duration of illness,
      and phobic avoidance behavior were found to be the best predictors of outcome.
      Conclusively, the present study confirms the most important predictors in
      patients with panic disorder.

PMID- 9186986
TI  - Diffuse lung disease: a view for the future.

PMID- 9186985
TI  - Sarcoidosis and transplantation.
AB  - BACKGROUND AND AIM OF WORK: Organ transplantation is an accepted treatment for
      patients with end-stage organ failure. There is limited information about
      transplantation in patients with sarcoidosis. While there has been no systematic
      study of transplantation in sarcoidosis, there have been several reports of
      patients with sarcoidosis undergoing organ transplantation. The purpose of this
      review is to analyze the available literature. METHODS: We reviewed the
      literature regarding transplantation of kidney, liver, heart, heart-lung and lung
      in patients with sarcoidosis with attention to survival, complications and the
      incidence of recurrence of sarcoidosis in the transplanted organ and at distant
      sites. RESULTS: Survival and complication rates are similar to those of patients
      undergoing transplantation for other indications. Recurrence of pulmonary
      sarcoidosis has been estimated to be 47% following lung transplantation. The
      published cases represent a fraction of the patients reported to the
      International Registry maintained by the United Network of Organ Sharing (UNOS).
      CONCLUSIONS: Transplantation can be carried out safely in patients with
      sarcoidosis. Recurrence is frequent, often asymptomatic, and does not compromise
      graft function or patient survival. Radiographic abnormalities or symptoms
      associated with recurrence are responsive to increased adrenocorticosteroid
      therapy. Exacerbation of sarcoidosis in transplant recipients occurs in the
      setting of intense immunosuppression.

PMID- 9186987
TI  - Is the different T helper cell activity in sarcoidosis and extrinsic allergic
      alveolitis also reflected by the cellular bronchoalveolar lavage fluid profile?
AB  - BACKGROUND: Sarcoidosis is generally characterized by a CD4+ lymphocyte
      predominance in bronchoalveolar lavage fluid (BALF), whereas in extrinsic
      allergic alveolitis (EAA) a CD8+ lymphocyte predominance is found. However, we
      have previously demonstrated an increase in CD4+ lymphocytes in BALF obtained
      from EAA patients as well. The aim of this study was to evaluate whether in
      sarcoidosis and EAA the BALF cellular profile-even without the help of cytokine
      detection-might reflect differences in the CD4+ T-lymphocyte subpopulations, i.e.
      T helper (TH)-1 and TH2 lymphocytes. METHODS: For this purpose, we analyzed BALF
      analysis results obtained from 77 nonsmoking patients with histologically proven
      sarcoidosis and 54 nonsmoking patients suffering from EAA. RESULTS: Patients with
      EAA showed the highest mean absolute numbers of lymphocytes, CD8+ as well as CD4+
      T lymphocytes, whereas the percentage of CD4+ T lymphocytes in BALF was low. In
      contrast, patients with sarcoidosis showed the lowest absolute and relative
      number of CD8+ T lymphocytes, the highest percentage of CD4+ T lymphocytes and
      CD4+/CD8+ ratio. Moreover, patients with Lofgren's syndrome demonstrated an
      alveolitis suggesting a TH1 lymphocyte-subset-like predominant related profile,
      characterized by lower numbers of eosinophils and mast cells, whereas sarcoidosis
      patients with respiratory symptoms formed a more mixed TH1/TH2 pattern. Patients
      with EAA showed a cellular BALF profile suggesting a functional predominance of
      TH2 lymphocytes. CONCLUSION: These preliminary data suggest a different
      distribution of the CD4+ T lymphocyte subtypes characterized by a functional
      heterogeneity of CD4+ T lymphocytes between-as well as within-these various
      pulmonary disorders. The exact role of this imbalance of TH1 and TH2-like
      activity in the lung with regard to the pathogenesis and prognosis needs to be
      further elucidated.

PMID- 9186988
TI  - Quantitative evaluation of the IL-1 beta and IL-1 receptor antagonist obtained
      from BALF macrophages in patients with interstitial lung diseases.
AB  - Our previous reports demonstrated the concomitant release of IL-1 beta and IL-1
      inhibitory activity in the culture supernatants of BALF macrophages in both
      healthy subjects and patients with interstitial lung diseases. IL-1 inhibitory
      activities decreased in healthy smokers (HS), and patients with sarcoidosis
      (Sar), or idiopathic pulmonary fibrosis (IPF), compared with those in healthy
      nonsmokers (HNS), though an increase in IL-1 beta release was not detected. IL-1
      inhibitory activity was mainly characterized as IL-1 receptor antagonist (IL
      1ra). In this study, we confirmed a decrease in IL-1ra in terms of the amounts of
      protein (enzyme-linked immunoassay) and gene transcripts (reverse transcriptase
      polymerase chain reaction followed by high performance liquid chromatography).
      Imbalance between IL-1ra and IL-1 beta was expressed as a molar ratio of IL
      1ra/IL-1 beta protein: (Sar; 4.20 +/- 2.06, IPF; 4.26 +/- 3.41, HS; 3.44 +/- 3.09
      versus NS 8.33 +/- 2.77: P < 0.001). These results were similar in terms of the
      amounts of gene transcripts. In conclusion, the imbalance of IL-1 beta and IL-1ra
      production was confirmed at three levels: biological activity, amounts of
      protein, and gene transcript obtained from BALF macrophages in chronic
      inflammatory processes in the lungs.

PMID- 9186989
TI  - A simple radiographic scoring method for monitoring pulmonary sarcoidosis:
      relations between radiographic scores, dyspnoea grade and respiratory function in
      the British Thoracic Society Study of Long-Term Corticosteroid Treatment.
AB  - BACKGROUND: We used a simple semi-quantitative radiographic scoring system for a
      controlled prospective study of long term corticosteroids in pulmonary
      sarcoidosis, conducted by the British Thoracic Society. METHODS: Radiographic
      opacities were described in 4 categories: reticulo-nodular shadows [R], mass
      opacities [M], confluence [C], and shadows associated with possible pulmonary
      fibrosis [F]. The extent of each type was scored on a 0-4 scale by quartiles, and
      profusion by a 0-4 scale as absent, minimal (just perceptible), mild moderate or
      gross. Combined scores for each film were derived by multiplying the extent and
      profusion for each type of opacity. In the study 149 patients were examined at
      entry and periodically over a 5-year period. Using the whole study population we
      examined the relationship between the radiographic scores for extent and
      profusion, how predominant types change with time and how the scores correlated
      with other indices of disease severity. RESULTS: R was the predominant
      abnormality throughout the study with a strong correlation between extent and
      profusion. Significant correlations in the expected directions were demonstrated
      between the R and F scores and a dyspnoea score, spirometry and TLCO, both at
      study entry, after 6 months and after 5 years. Similarly, there were significant
      relations between changes in spirometry and TLCO over five years and changes in R
      and F Scores. CONCLUSION: This scoring system would seem to be suitable, perhaps
      after further validation work, for other prospective clinical studies.

PMID- 9186990
TI  - Sleep apnea in sarcoidosis.
AB  - BACKGROUND AND AIM OF WORK: Sleep apnea is reported to occur in 2-4% of the
      general population. Patients with sarcoidosis are at increased risk for sleep
      apnea, possibly due to factors such as steroid use, neurosarcoid, or upper airway
      obstruction. METHODS: In order to determine the prevalence and risk factors for
      sleep apnea in sarcoidosis patients, we studied 83 consecutive patients with
      sarcoidosis seen over a six-week time period. Patients were screened using the
      Epworth Sleepiness Scale questionnaire and the age, sex, race, weight, and
      medications were recorded. The presence of previously diagnosed sleep apnea,
      neurosarcoid, lupus pernio, and sinus disease were also noted. A control group of
      91 patients seen in general pulmonary clinics were similarly screened. Patients
      with a positive sleep questionnaire were referred for sleep studies. RESULTS: A
      total of 14 sarcoid patients (17%) were found to have sleep apnea, which was
      significantly higher than our control group with 3/91 (3%, p < 0.001). The
      presence of lupus pernio was significantly more frequent in the sleep apnea
      group. Although 5/51 (10%) female sarcoid patients had sleep apnea, overall it
      was more frequent in male sarcoid patients. CONCLUSIONS: Sleep apnea was frequent
      in sarcoid patients and was associated with lupus pernio.

PMID- 9186991
TI  - Non invasive evaluation of the inflammatory activity in sarcoidosis with high
      resolution computed tomography.
AB  - PURPOSE: The value of high resolution computed tomography (HR-CT) in the
      recognition of pathologic changes of the lung parenchyma, especially in the
      diagnosis of sarcoidosis, is well established. The importance of these findings
      in regard to the inflammatory activity is not sufficiently documented, also
      because a direct histologic correlation is seldom possible. METHOD: In a
      prospective study twenty-one patients with suspected or known sarcoidosis were
      evaluated. The diagnostic work up comprised the clinical examination, lung
      function tests, the radiological evaluation, including GH-CT, and bronchoscopy
      for bronchoalveolar lavage (BAL) and transbronchial biopsy. RESULTS: The
      comparison of the HR-CT findings, like pathologic appearance of the
      bronchovascular bundle and intraparenchymal nodules, with serologic and BAL
      parameters yielded high correlation coefficients with the total cell count in BAL
      and sIL-2R, and moderate correlations with the lavage lymphocyte count and the
      activity markers, like T4/T8 ratio, IL-2R and HLA-DR expression. CONCLUSION: As a
      non invasive method, HR-CT depicts pathologic findings of the lung parenchyma
      which are associated with the inflammatory activity of sarcoidosis.

PMID- 9186992
TI  - Course of asymptomatic liver involvement in sarcoidosis: role of therapy in
      selected cases.
AB  - AIM: Although granulomatous involvement of the liver with functional
      abnormalities is widely known, the course of these abnormalities is not clearly
      known. The study was designed to find out the incidence and course of
      asymptomatic liver function abnormalities. METHODS: From 1990-1995, during the
      five year period, 44 (35.2%) of 125 patients with sarcoidosis at LAC + USC
      Medical Center had liver involvement. Liver enzyme abnormalities aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase
      (AP) were taken as criteria for liver involvement: 41 (93%) patients had elevated
      AP, 22 (50%) showed elevated ALT, and 24 (54.5%) had elevated AST. RESULTS: 25 of
      44 patients received treatment; 12 (48%) showed improvement in liver enzymes and
      13 (52%) remained unchanged. Ten (7%) of 13 patients, who did not receive any
      treatment, also improved. During the same period at USC University Hospital 18
      (25%) of 72 had liver involvement. Twelve patients received treatment; 6 (50%)
      patients showed improvement in liver enzymes. One of 3 patients, who did not
      receive treatment, improved. 5 (41%) developed complications due to steroids.
      CONCLUSION: Liver involvement is common in African American patients with
      sarcoidosis. Social and economic status do not seem to influence the liver
      involvement. In men the age distribution has an early peak. The outcome of
      patients who receive treatment remains similar, as far as liver function is
      concerned, suggesting that most of the patients with liver involvement undergo
      natural remission. Unless the patient has progressive liver dysfunction, it is
      advisable to monitor liver enzymes periodically and obtain liver biopsies only if
      clinically indicated. In patients who need treatment, it is reasonable to try
      options other than steroids in view of severe corticosteroid related
      complications.

PMID- 9186993
TI  - Pulmonary sarcoidosis: spirometric correlation with transbronchial biopsy.
AB  - We studied the relationship between the histopathology obtained by trans
      bronchial lung biopsy (TBLB), and spirometric indices in 28 patients of pulmonary
      sarcoidosis in whom the diagnosis was confirmed. There was a rough correlation
      between FVC and the histologic granuloma load, interstitial inflammation and the
      overall histopathological score. Radiological features did not correlate with
      either spirometry or histopathology.

PMID- 9186994
TI  - Wegener's presenting as submandibular swelling.
AB  - We describe a patient in whom bilateral swelling of submandibular glands was the
      initial manifestation of limited Wegener's disease. The diagnosis was based on
      positive anti-neutrophil cytoplasmic antibody [C-ANCA], dense inflammatory
      infiltrate predominantly of lymphocytes in submandibular glands, presence of non
      caseating ill-formed granulomas in transbronchial biopsy and resolution of
      symptoms following immuno-suppressive treatment.

PMID- 9186995
TI  - Sarcoidosis in an Australian aborigine and a Torres Strait Islander.
AB  - BACKGROUND AND AIM: This is the second case report of sarcoidosis in an
      Australian Aborigine and the first in a Torres Strait Islander. The Australian
      Aborigine had atypical superior mediastinal lymphadenopathy and uveitis while the
      Torres Strait Islander had persistent pulmonary disease requiring oral
      corticosteroids. CONCLUSIONS: Indigenous Australians appear to be rarely affected
      by sarcoidosis. However, it is common in people of Celtic origin. The presence of
      a European (Celtic) ancestor in the family tree of both individuals suggests that
      yet unknown genetic factors may be important in the pathogenesis of their
      disease.

PMID- 9186996
TI  - Positive Lyme titers in a patient with active sarcoidosis.

PMID- 9186997
TI  - Sarcoidosis with thyroid involvement.

PMID- 9186998
TI  - Periampullary carcinoma in a patient with sarcoidosis.

PMID- 9186999
TI  - The influence of vertigo, hearing impairment and tinnitus on the daily life of
      Meniere patients.
AB  - The aim of this questionnaire study was to investigate the impact of the symptoms
      in Meniere's disease on the daily life of patients and to analyse the
      relationships between the cardinal symptoms and environmental, emotional and
      activity factors. The study comprised 514 patients, recruited from two different
      sources. The results showed that vertigo, hearing impairment and tinnitus had a
      strong negative influence on the daily life of patients. Seventy-five percent of
      the subjects avoided certain everyday activities or situations because of the
      disease. However, the correlation between discomfort and reported satisfaction
      with life was moderate. Most of the subjects experienced premonitory symptoms of
      the attacks and 80% reported relations between external factors and vertigo
      attacks.

PMID- 9187000
TI  - Perinatal asphyxia, hypoxia, ischemia and hearing loss. An overview.
AB  - Birth hypoxia, asphyxia and ischemia have often been thought to be major causes
      of early hearing loss or deafness. The purpose of the present review is to focus
      on the role of these particular factors for perinatal auditory disorders. On the
      whole, only a small proportion of neonatal hearing loss is caused by perinatal
      factors. The exact etiology of neonatal hearing loss in children with complicated
      deliveries is difficult to evaluate due to the large number of causative factors
      that might be involved. After reviewing the literature covering the past 15-20
      years, it is not possible to say that we understand the relative importance of
      different factors and their interactions. However, in the majority of studies,
      birth asphyxia is not correlated with hearing loss in babies with complicated
      deliveries Prolonged artificial ventilation, the presence of severe hypoxic
      ischemic encephalopathy or persistent pulmonary hypertension are important
      factors. The brain is more susceptible to anoxia than the ear and both are more
      likely to be damaged after prolonged pre-, peri- and postnatal hypoxia-ischemia
      than pure hypoxia during delivery. Perinatal hypoxia is more likely to cause a
      temporary hearing loss than a permanent one. Preterm babies are more vulnerable
      than term babies. The total number of risk factors, e.g. medicated by total
      length of stay in the neonatal intensive care unit and length of artificial
      ventilation, is the best predictor of risk for hearing loss of perinatal origin.
      The similarities between hearing loss and cerebral palsy are pointed out; only 8%
      of the cases of cerebral palsy are considered to be caused by conditions during
      delivery.

PMID- 9187001
TI  - Attempts to develop an efficient speech test in fully modulated noise.
AB  - An earlier developed speech test with sentences in noise (Hagerman. 1982) was
      modified in an attempt to further increase its efficiency. The noise was thus
      changed to be fully modulated and the speech-to-noise ratio of each word was
      controlled in order to make all the words equally difficult both within and
      between lists. The new version was tested on 10 normal-hearing subjects. The 10
      lists were equally difficult, but compared to the old material the reliability
      was worse, the learning effect was greater, and the slope of the intelligibility
      function was less than half despite efforts to maintain the quality of the test.
      Identical masking signals for identical words in the various lists seem to
      increase the learning effect. The strongly modulated noise seems to give shallow
      intelligibility functions for separate words and thus also for complete lists.

PMID- 9187002
TI  - Hearing in the elderly > or = 80 years of age. Prevalence of problems and
      sensitivity.
AB  - This article is part of an epidemiological study on hearing in an urban
      population > or = 80 years of age, and concentrates on the prevalence of hearing
      problems and hearing sensitivity as a function of age and gender. Prior to the
      study, 2915 residents aged 80+ from the Valby area in Copenhagen were selected
      for investigation and subdivided into two groups. The first group, comprising n =
      859 subjects previously provided with HA, and the second group, resulting from an
      invitation mailed to n = 565 subjects, were matched according to the age and
      gender distribution of the population, i.e. 24% males and 76% females. Among
      these, only 41% at a median age of 84 years, range 80-96, accepted the
      invitation, being significantly younger than the non-attenders. The estimated
      prevalence of self, reported hearing problems ranged between 33 and 66%,
      increasing with increasing age. Significant differences were found in the hearing
      sensitivity as a function of gender, i.e. the hearing in the low-frequency area <
      1 kHz is better, whereas the hearing sensitivity at > 2 kHz is significantly
      worse in males compared with females. The speech recognition score (SRS) was
      significantly higher in females compared with males, and a comparison between
      ears supports the finding that the right ear speech recognition score is better
      than the left. The study demonstrates the difficulties in obtaining reliable
      epidemiological data on the hearing in the elderly > or = 80 years, which
      represents an obstacle for the planning of appropriate hearing health services
      directed towards this age group, and collaborative studies are suggested in order
      to accumulate more knowledge.

PMID- 9187004
TI  - Word recognition in continuous noise, interrupted noise, and in quiet by normal
      hearing listeners at two sensation levels.
AB  - The effect of presentation level on word recognition performance-intensity
      functions in continuous and interrupted broadband noise and in quiet was
      explored. Normal-hearing participants were tested at 30 and 50 dB sensation
      levels (SLs). Performance-intensity functions in both noises were determined at
      signal-to-noise ratios (S/Ns) of 10, 5, 0, -5, -10, -15, and -20 dB. There was no
      effect of SL presentation on word recognition performance in quiet (p = 0.136). A
      significant main effect was observed for S/N in both continuous and interrupted
      broadband noise conditions (p < 0.0001). Performance increased with increases in
      S/N regardless of the competing noise condition. A significant main effect for SL
      presentation was only observed in the interrupted noise condition (p = 0.0019).
      That is, performance was higher for the 50 SL for the interrupted noise condition
      only. It is suggested that the observed difference in performance in interrupted
      noise at different SLs offers additional evidence for level-dependent, temporal
      masking phenomena.

PMID- 9187003
TI  - Hearing thresholds in four-year-old children with weak or no transient-evoked
      otoacoustic emissions.
AB  - Play audiometry is part of the general developmental screening covering 4-year
      old children in the city of Malmo (Sweden). In an open study, 10% of the cohort
      was tested with transient-evoked otoacoustic emissions (TEOAEs), using the ILO88
      system. The aim was to reveal a hearing loss exceeding 25 dB HL in 4-year-old
      children. As the first step in determining whether emissions can be used as an
      efficient method of screening for hearing loss, 295 children were tested with
      TEOAEs. Audiometry was performed in 160 children. Audiometry was not performed if
      the TEOAEs were strong (> or = 10 dB SPL) in both ears. In the group with TEOAEs
      of 8.8dB SPL or greater, all ears tested with audiometry had a pure-tone average
      (PTA) of 25 dB HL or better. Twenty-one percent of the ears had TEOAEs < or = 0
      dB SPL. Only 9% of the ears had a hearing threshold exceeding 25 dB HL (PTA). In
      conclusions, the number of pathological TEOAE results was much larger than the
      number of pathological audiograms, making TEOAEs too sensitive to use as a single
      screening test, but the method may be used as first-line screening.

PMID- 9187005
TI  - Clinical evaluation of three different loudness scaling protocols.
AB  - Loudness scaling has recently attracted much attention as a valuable clinical
      tool for acquiring reliable knowledge about loudness perception. This information
      can be used for diagnostic and rehabilitative purposes. In this study a loudness
      scaling module implemented in a new PC-based audiological test system was
      comprehensively tested. The system has proven to be a reliable and useful tool in
      a clinical environment. The described 'Default' loudness scaling protocol seems
      to represent an appropriate set of parameters. A comparison between this protocol
      and two other protocols available for clinical use indicates that the 'Default'
      protocol presents the same consistency of subject response as the 'IHAFF'
      protocol, and a better consistency than the 'LGOB' protocol. Regarding time
      consumption, the 'Default' protocol is superior to the 'IHAFF' protocol and
      comparable to the 'LGOB' protocol.

PMID- 9187006
TI  - Impulse noise and acute acoustic trauma in Finnish conscripts. Number of shots
      fired and safe distances.
AB  - This prospective study of acute acoustic trauma (AAT) from exposure to impulse
      noise during compulsory military service focused on three issues the number of
      shot or explosion impulses that the conscript was exposed to at the time of AAT,
      distance of injured ear from causal firearm, and the circumstances under which
      AAT occurred protected ears. The series includes 449 consecutive, verified cases
      of AAT seen at the Central Military Hospital in Helsinki, Finland, in the period
      1989-1993. AAT usually occurred during combat training (87%) as a result of
      exposure to impulses from small arms (83%). In 41%. AAT was caused by a single
      shot or detonation impulse. As many as 92% of all AATs occurred within 2 m of the
      causal firearm. Fourteen percent were wearing hearing protectors when the
      accident took place, but every third had badly fitting protectors or had
      neglected safety regulations and used insufficient protection. Of all AATs caused
      by one noise impulse in protected ears. 83% were attributable to heavy arms and
      only 14% to small arms. The results of the study suggest that combined use of
      earmuffs and earplugs in association with a safe distance of over 5 m from the
      noise source gives adequate protection against AAT. However, for conscripts using
      certain heavy arms e.g. hazooka. more effective hearing protection should be
      developed.

PMID- 9187007
TI  - Verbal memory impairment in schizophrenia: no sparing of short-term recall.
AB  - Verbal memory function was assessed in 27 schizophrenic patients and 19 healthy
      control subjects matched for premorbid IQ and age using a test battery comprising
      measures of short-term, long-term and source memory. Patients were also rated for
      positive and negative symptoms. Results indicated that the patient group evinced
      poorer performance on all tests of short-term memory, and most tests of long-term
      memory, and that these differences remained when current IQ was introduced as a
      covariate. Within the patient group, overall verbal memory performance was
      associated only with a negative symptoms. Results are discussed in the context of
      a generalised neuropsychological deficit in schizophrenia.

PMID- 9187008
TI  - Visually-guided saccadic eye movements in adolescents at genetic risk for
      schizophrenia.
AB  - Visually-guided saccades of 21 offspring of schizophrenic parents and 21
      individually matched controls were compared with regard to the frequency of
      occurrence of saccadic hypometria and hypermetria, non-fixations, and omissions
      of target jumps. Target steps ranged from 10 to 60 degrees, and interstimulus
      intervals averaged 2.5 s; subjects were promised financial reward depending on
      performance. Recordings were carried out at the subjects' homes. To screen for
      cognitive abilities and psychopathological behavior, subjects were tested by
      means of an intelligence scale and a behavioral checklist. With large target
      steps (40-60 degrees), the high-risk group made significantly more grossly
      hypometric saccades (gain < or = 0.8) than the control group; responses to small
      target steps (10-30 degrees) exhibited a similar, albeit statistically not
      significant, trend. There were no significant differences with regard to the
      occurrence of hypermetria. Non-fixations scored marginally higher in the high
      risks as compared to controls, but this was again not a significant difference.
      The incidence of omissions of saccades was very low in both groups. The results
      of the study suggest that subjects at genetic risk for schizophrenia may differ
      from controls by an increased incidence of conspicuously hypometric saccades.
      Clearly, this difference is not caused by a deficit of the saccadic motor
      circuitry proper; comparison to control data obtained with a similar experimental
      protocol suggests that it probably reflects an impaired internal control of
      saccades in the presence of distraction and stress. The relevance of saccades as
      indicators of a possible schizophrenic vulnerability is discussed.

PMID- 9187009
TI  - The number of triplet repeats in five brain-expressed loci with CAG repeats is
      not associated with schizophrenia.
AB  - We have previously shown that large expansions of CAG (CTG) triplets are
      associated both with schizophrenia itself and with an early age-at-onset of the
      disease. However, the repeat expansion detection (RED) method used did not
      provide a chromosomal location for the expanded region(s) (Morris et al., 1995).
      In a further study of our schizophrenic and control patients, we have now
      examined the length of the repeated sequence in five loci that are expressed in
      brain and are known to contain CAG repeat regions (Li et al., 1993). No enlarged
      repeat regions were identified; it is unlikely therefore that expansions at any
      of these five loci can account for expansions of up to 136 triplets identified by
      the RED method.

PMID- 9187010
TI  - No association of the Ser/Cys311 DRD2 molecular variant with schizophrenia using
      a classical case control study and the haplotype relative risk.
AB  - Arinami et al. (1994) reported an association between the Ser311/Cys311 variant
      of the DRD2 gene and schizophrenia in a Japanese population. We did not find
      statistically significant differences in the distribution of the allele
      frequencies between schizophrenics (103) and controls (97) in a case-control
      sample (chi 2 = 2.07; p = 0.150) or in 64 nuclear families with the haplotype
      relative risk (HRR) design (chi 2 = 0.13; p = 0.718). Our results seem to exclude
      a main involvement of this variant of the dopamine D2 receptor gene in the
      etiopathogenesis of schizophrenia.

PMID- 9187011
TI  - CSF IL-1 and IL-2 in medicated schizophrenic patients and normal volunteers.
AB  - It is clear that cytokines exert a variety of modulatory actions on the central
      nervous system. As part of our work exploring the relationship between immune
      activation and psychosis, we measured cerebrospinal fluid (CSF) IL-1 alpha and IL
      2 levels in 60 medicated schizophrenic patients and in 21 normal volunteers using
      a competitive enzyme immunoassay. The two groups did not differ significantly in
      their mean cytokine levels: 1.01 (0.149) ng/ml (patients) vs. 1.28 (0.150) ng/ml
      (controls) for IL-1 alpha and 0.970 (0.038) ng/ml (patients) vs. 1.25 (0.086)
      ng/ml (controls) for IL-2. There was a significant positive correlation between
      CSF IL-1 alpha and IL-2 levels for all subjects (r = 0.50, n = 44, p = 0.0001).

PMID- 9187012
TI  - Depressive symptoms in acute schizophrenic inpatients.
AB  - Prospective and longitudinal assessment of depressive, positive, and negative
      symptoms were performed on 86 newly admitted schizophrenic patients. The
      improvement of depressive symptoms was significantly correlated with the
      improvement in positive symptoms, but did not correlate with the improvement in
      negative symptoms. However, depressive symptoms were heterogeneous. Principal
      components analysis was used to subdivide depressive symptoms into five factors.
      The improvement of the depression-anxiety factor was significantly associated
      with improvement of positive symptoms. On the other hand, improvement of negative
      symptoms was significantly related to that of the reduced activity factor. The
      change in hypochondriasis had a significant positive correlation with the change
      in positive symptoms and had a significant negative correlation with the change
      in negative symptoms. Changes in the other factors of depressive symptoms did not
      appear to be associated with changes in positive or negative symptoms. The
      present findings suggest that the various depressive symptoms associated with
      acute schizophrenia may have different pathophysiological origins.

PMID- 9187013
TI  - Detecting comorbid substance misuse among people with schizophrenia in the
      community: a study comparing the results of questionnaires with analysis of hair
      and urine.
AB  - Substance misuse among people with schizophrenia is thought to be common and to
      adversely affect the outcome of the illness. The shortcomings of studies in this
      area include patient samples that are not epidemiologically-based, and methods
      for detecting substance misuse that have serious limitations. We investigated the
      frequency and severity of substance misuse among people with schizophrenia living
      in the community in London. Interviews were conducted with a community-based
      sample of 39 people with schizophrenia aged 35 years or less, living in Inner
      London. The assessments included ratings of psychopathology, movement disorders
      and substance misuse, and co-informant histories. Urine and hair specimens were
      analysed for a range of substances. Urine samples were collected from 37 patients
      and hair samples were provided by 36 patients. Comorbid substance misuse was
      reported or detected in 63% of the sample. The information elicited using a
      structured questionnaire for both informants and subjects represented an under
      estimate of psychostimulant misuse and opiate misuse compared with the results
      obtained by hair or urine analysis. Hair analysis revealed that 12 (33%) of those
      patients providing samples had covertly abused amphetamines, opiates or cocaine
      in the previous 3 months. The study demonstrated that hair analysis is a well
      tolerated, sensitive test for substance misuse. The technique has several
      advantages over questionnaires and urine analysis for clinical and research
      purposes. Further applications include the assessment of comorbid substance use
      in particular groups of patients with schizophrenia, such as during first-episode
      or psychotic relapse, or those with forensic problems or apparent resistance to
      treatment.

PMID- 9187014
TI  - How do men with schizophrenia fare at work? A follow-up study from India.
AB  - Occupational activity, an indicator of the functional status of an individual, is
      a major component in the long-term management of schizophrenia. The work
      functioning of 40 first-episode male schizophrenic patients was assessed
      prospectively every year over a period of 10 years. The comprehensive evaluation
      of occupational outcome measured in terms of duration of employment, quality of
      work done, and level of earned income was good in 53% of the patients, comparable
      to figures from developed countries. This outcome was not related to many of the
      socio-demographic and clinical variables but was strongly associated with overall
      clinical, social and marital outcome. The educational and economic status of the
      study group, the type of work available to them, and the compelling need for men
      to be the wage-earners in the Indian situation are discussed as influencing the
      findings of the study.

PMID- 9187015
TI  - Qualitative cerebral morphology in schizophrenia: a magnetic resonance imaging
      study and systematic literature review.
AB  - Patients with schizophrenia have larger lateral ventricles, less cerebral
      substance and smaller mesial temporal lobe structures than groups of normal
      controls, but it has proved difficult to link these volumetric abnormalities with
      clinical features of the illness. Such quantitative techniques may overlook
      qualitative abnormalities of importance. We therefore compared a
      neuroradiologists' clinical assessment of gross structural abnormalities,
      generalised 'atrophy' and high intensity signal (HIS) foci, as detected on the
      first and second echo of a long TR sequence, in 42 patients with schizophrenia
      (22 treatment responsive, 20 treatment resistant) and 50 normal controls. The
      schizophrenic group included two (5%) subjects with gross lesions, two (5%) with
      cerebellar atrophy, 21 (52%) with at least a mild degree of cerebral atrophy, and
      15 (38%) with one or more HIS foci; the comparable figures in the controls being
      2, 0, 2 and 14%, respectively. Controlling for age, patients with schizophrenia
      had a substantially elevated rate of cerebral atrophy (odds ratio (OR) = 11.7, p
      < 0.0001). Treatment-resistant schizophrenics showed a tendency (OR = 2.8, p =
      0.06) to greater atrophy than those who were treatment responsive, whereas our
      previous volumetric study showed no such difference. In contrast, the presence of
      HIS foci was only related to age. The degree of atrophy was correlated with the
      number of HIS foci (r = 0.31, p = 0.014). Taken together with previous studies,
      these findings demonstrate the value of qualitative examination of MRI images in
      patients with schizophrenia.

PMID- 9187016
TI  - Effects of TAK-029, a novel GPIIb/IIIa antagonist, on arterial thrombosis in
      guinea pigs, dogs and monkeys.
AB  - The antithrombotic and bleeding time (BT) prolonging effects of TAK-029, a novel
      GPIIb/IIIa antagonist, were examined in three arterial thrombosis models. In
      guinea pigs, TAK-029 at 30 micrograms/kg (i.v.) inhibited ADP-induced ex vivo
      platelet aggregation completely and prolonged BT to 4.5 times the control value 5
      min after administration, and it prevented thrombotic occlusion in 2 out of 5
      animals in a photochemically-induced basilar thrombosis model. TAK-029 at 100
      micrograms/kg (i.v.) prolonged BT more than 9 times 5 min after administration,
      and it prevented thrombus formation for over 60 min. In dogs, TAK-029 at 30
      micrograms/kg (i.v.) inhibited ADP-induced ex vivo platelet aggregation by 87% 5
      min after administration, and it prevented thrombotic occlusion in injured and
      stenosed coronary arteries for 22 min without prolonging the BT. TAK-029 at 100
      micrograms/ kg (i.v.) inhibited platelet aggregation completely and prolonged BT
      3.6 times 5 min after administration, and it prevented thrombus formation for
      over 45 min. In monkeys, TAK-029 at 10 micrograms/kg (i.v.) inhibited ADP-induced
      ex vivo platelet aggregation by 84% and prolonged BT 4.6 times 5 min after the
      administration, and it prevented thrombotic occlusion in injured and stenosed
      carotid arteries for 24 min. TAK-029 at 30 micrograms/kg (i.v.) completely
      inhibited platelet aggregation and thrombus formation for over 60 min, and it
      prolonged BT more than 7.3 times 60 min after administration. In conclusion, TAK
      029 exerted potent antithrombotic effects with BT prolongation in three different
      arterial thrombosis models. TAK-029 may be effective for the treatment of various
      arterial thrombotic diseases.

PMID- 9187017
TI  - Differential effects of the tyrosine kinase inhibitors on collagen type 1-induced
      platelet aggregation and adhesion to this protein.
AB  - Herbimycin A, lavendustin A, and methyl 2,5-dihydroxycinnamate were used to study
      the role of protein tyrosine kinases in collagen-platelet interaction. All three
      compounds produced a concentration dependent inhibition of platelet aggregation
      induced by collagen type I, characterized by values of IC50 equaled to 0.9, 10.0,
      and 5.0 microM, respectively. This effect was accompanied by strong inhibition of
      phosphorylation of p125FAK, p90, p72syk, p60c-arc, and p56lyn. In the absence of
      the inhibitors, phosphorylation of these proteins is evoked by aggregation of
      platelets. In addition to the antiaggregatory effect, the tyrosine kinase
      inhibitors reduced adhesion of platelets to collagen although to much lower
      extent than aggregation. Platelets which adhered to collagen showed also the
      presence of phosphorylated p125FAK, p90, p72syk, p60c-arc, and p56lyn. Of these
      proteins, the extent of phosphorylation of p90 was particularly high. Adhesion of
      platelets was associated with inhibition of phosphorylation of p125FAK, p60c-arc,
      and p56lyn only when high concentration of lavendustin A and methyl 2,5
      dihydroxycinnamate were used. Herbimycin A did not affect adhesion-evoked protein
      tyrosine phosphorylation. Phosphorylation of p90 and p72syk was not affected by
      inhibitors. This study indicates that collagen type I can induce different
      transmembrane signalling dependent upon whether platelet aggregates formation or
      adhesion of platelets to this protein occurs.

PMID- 9187018
TI  - Thrombin interaction with fibrin polymerization sites.
AB  - Thrombin is central to hemostasis, and postclotting fibrinolysis and wound
      healing. During clotting, thrombin transforms plasma fibrinogen into polymerizing
      fibrin, which selectively adsorbs the enzyme into the clot. This protects
      thrombin from heparin-antithrombin inactivation, thus preserving the enzyme for
      postclotting events. To determine how the fibrin N-terminal polymerization sites
      of A alpha 17-23 (GPRVVER) and B beta 15-25 (GHRPLDKKREE) and their analogs may
      interact with thrombin, amidolysis vs. plasma- and fibrinogen-clotting assays
      were used to differentiate blockade of catalytic site vs. other thrombin domains.
      Amidolysis studies suggest GPRVVER inhibition of thrombin catalytic site through
      hydrophobic interaction, and GPRVVER inhibited clotting. Neither GPRP nor VVER
      nor the B beta 15-25 homologs inhibited amidolysis. Contrary to heparin, acyl
      DKKREE promoted plasma-clotting, but inhibited fibrinogen-clotting. In addition,
      acyl-DKKREE reversed the anticoagulant effect of heparin (0.1 U/ml) in plasma.
      The results suggest fibrin B beta 15-25 interaction with thrombin, possibly by
      blocking the heparin-binding site. Together with the reported fibrin A alpha 27
      50 binding to thrombin, polymerizing fibrin appears to initially bind to thrombin
      catalytic site and exosite-1 through A alpha 17-50, and to another thrombin site
      through B beta 15-25. As these fibrin sites are also involved in polymerization,
      competition of the polymerization process with thrombin-binding could
      subsequently dislodge thrombin from fibrin alpha-chain. This may re-expose the
      catalytic site and exosite-1, thus explaining the thrombogenicity of clot-bound
      thrombin. The implications of these findings in polymerization mechanism and
      anticoagulant design are discussed.

PMID- 9187019
TI  - The inhibitory effect of heparin for vascular smooth muscle cell proliferation or
      migration is not mediated by u-PA and t-PA.
AB  - Previous works suggest the interesting possibility of an effect of heparin on
      vascular smooth muscle cell (SMC) replication and migration via a selective
      inhibition of the expression of t-PA and u-PA both of which may play major roles
      during intimal hyperplasia following endothelial injury. The present study was
      undertaken to evaluate in vitro the effect of heparin on the growth and migration
      of aortic SMC isolated from transgenic mice showing single inactivations of the t
      PA and u-PA genes comparatively to SMC isolated from control mice. With regard to
      serum-induced proliferation and migration, all cell types showed similar
      responses. On control cells, heparin inhibited in a dose-dependent manner the
      expression of both t-PA and u-PA protein and mRNA. Heparin however, similarly
      affected the mitogenic and chemotactic activity of FCS for SMC isolated from
      control, t-PA or u-PA-deficient mice therefore showing that heparin inhibits FCS
      induced SMC proliferation via mechanism(s) other than single inhibition of t-PA
      or u-PA expression by smooth muscle cells.

PMID- 9187020
TI  - The synthetic pentasaccharide SR 90107A/Org 31540 does not release lipase
      activity into the plasma.
AB  - The present study was designed to find out whether the synthetic pentasaccharide
      SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an
      antithrombotic agent, influences lipoprotein metabolism in rats as determined by
      plasma triglyceride (TG) lipase activity. A comparison with three clinically used
      sulphated polysaccharides-unfractionated heparin (UFH), low molecular weight
      heparin (LMWH) and pentosan polysulphate (PPS)- was performed. UFH evoked a dose
      dependent increase in plasma TG lipase activity which plateaued at doses > or = 1
      mg/kg i.v.. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1
      mg/kg i.v., but the maximum lipase releasing effect at 3 mg/kg i.v. was identical
      for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at
      single i.v. doses up to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org
      31540 (1 mg/kg s.c. for 9 days) revealed no influence on the lipase releasing
      effect of UFH (1 mg/kg i.v. on day 10). These results demonstrate that SR
      90107A/Org 31540 does not influence lipid metabolism in rats through lipase
      release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and
      LMWH in clinical situations where an anticoagulant/antithrombotic effect is
      desired, but both an increase in plasma free fatty acids and atherogenic
      alterations of lipoprotein metabolism are considered harmful.

PMID- 9187021
TI  - Homocysteine in Greenland Inuits.
AB  - Patients with homozygous homocystinuria are at greatly increased risk for
      development of atherosclerosis and thrombosis (1). Elevated plasma levels of
      homocysteine (HCY) are caused by reduced enzymatic catabolism or reduced
      enzymatic remethylation of HCY, due to either hereditary enzyme defects or to
      nutritional deficiencies of vitamins functioning as cofactors. However, several
      recent studies have suggested that persons with mildly elevated plasma levels of
      HCY also are at increased risk for coronary heart disease. (2-4). There are some
      indications that dietary n-3 polyunsaturated fatty acids (PUFAs) may offer
      protection against coronary heart disease (5-6). Several mechanisms may be
      involved, including beneficial effects of n-3 PUFAs on plasma lipids, platelet
      and leukocyte reactivity, blood pressure and vasoreactivity (7). Interestingly,
      Olszewski el al. recently found HCY-levels to be lowered 36% in 15 type IIa or
      IIb hyperlipemic men by n-3 PUFA supplementation. A possible beneficial effect of
      n-3 PUFA on the incidence of coronary heart disease was initially suggested from
      studies in Greenland Inuits by our group (8). We therefore investigated plasma
      levels of homocysteine in a group of traditionally living Greenland Inuits with a
      diet consisting mainly of marine food and with a very high content of n-3 PUFAs.

PMID- 9187022
TI  - The influence of isoprostanes on ADP-induced platelet aggregation and cyclic AMP
      generation in human platelets.
AB  - Isoprostanes are eicosanoids that are non-enzymatic products of free radical
      catalyzed peroxidation of arachidonyl containing phospholipids (1). They are
      subsequently released from the site of generation as esters of phospholipid
      (bound) or through the action of phospholipase(s) A2 in free form (2). One F2
      isoprostane whose formation is highly favored is 8-iso-PGF2 alpha which has been
      shown to be a potent pulmonary and renal vasoconstrictor (3,4). Actions of 8-iso
      PGF2 alpha were demonstrated to be mediated through a receptor related to but
      probably distinct from the thromboxane (TXA2)/endoperoxide (PGH2) receptor (5).
      Although 8-epi-PGF2 alpha is a potent agonist of TXA2/PGH2 receptors in vascular
      smooth muscle, interestingly it acts primarily as an antagonist of TXA2/PGH2
      receptors on both human and rat platelets (6). There is also evidence for the
      generation of D- and E-ring isoprostanes (7) and their receptor-mediated action
      on smooth muscle cells (8) and platelets (9). Recent reports support the
      hypothesis that E2-isoprostane receptors are distinct from TXA2/PGH2 receptors,
      suggesting at least different subtypes, one of these specifically recognizing E2
      isoprostanes (9). Isoprostanes have been suggested to be useful markers for
      oxidant injury. For example, F2-isoprostanes were significantly elevated in
      plasma of rats during reperfusion after hepatic ischemia (10) and in patients
      with hepatorenal syndrome (11). It has been suggested that the release of F2
      isoprostanes from oxidized LDL in macrophages could be a contributory factor in
      the development of atherosclerosis and at sites of inflammation, locally elevated
      levels of isoprostanes could contribute to blood cell activation. In this study
      we investigate possible pro- or antiaggregatory properties of various F- and E
      type isoprostanes on human platelets.

PMID- 9187023
TI  - The effect of protamine sulphate on plasma tissue factor pathway inhibitor
      released by intravenous and subcutaneous unfractionated and low molecular weight
      heparin in man.
AB  - Heparin, a negatively charged sulphated glycosaminoglycan, is clinically the most
      important antithrombotic drug. Heparin augments the inhibitory activity of
      antithrombin (AT) towards thrombin, factor Xa (FXa) and other activated clotting
      enzymes. Tissue factor pathway inhibitor (TFPI) is an endogenous heparin
      releasable three domain Kunitz-type coagulation inhibitor which inhibits the
      crucial tissue factor-factor VIIa (TF-FVIIa) dependent coagulation pathway in the
      presence of FXa. The importance of the TF-FVIIa pathway and TFPI has recently
      been reviewed (1). TFPI is located to different vascular pools, the largest being
      the vascular endothelium from where TFPI can be released dose-dependently to the
      blood by heparins (2). TFPI is speculated to contribute to the anticoagulant
      properties of heparins, but to which degree is not yet fully understood. In
      recent years low molecular weight heparins (LMWH) have proven to be effective and
      safe both for prophylactic (3) and therapeutic treatment (4) of deep vein
      thrombosis (DVT). Protamine is the least toxic and clinically most commonly used
      antidote to heparin. However, in vitro and in vivo LMW heparinized blood is not
      fully neutralized by protamine, as substantial anti-Xa activity remains following
      neutralization (5). This post-protamine effect has been shown to be partly TFPI
      dependent when measured in a dilute TF-dependent assay (6,7). We undertook this
      in vivo study on healthy volunteers in order to investigate whether TFPI released
      by UH or LMWH (intravenous (iv) or subcutaneous (sc)) remains in the circulation
      following neutralization of the heparin activity with protamine sulphate (PS). We
      measured TFPI by three different methods-chromogenic activity, anticlotting
      activity and a new antigen assay specific for full-length and three-domain TFPI.

PMID- 9187024
TI  - Equine babesiosis associated with strenuous exercise: clinical and pathological
      studies in Jordan.
AB  - Clinical, haematological and pathological studies were undertaken in Jordan in a
      stud of 103 racing horses clinically suffering from babesiosis and apparently
      healthy animals. Out of 47 horses which participated in strenuous exercise, three
      mares showed sudden onset of immobility and reluctance to move and two mares
      died. Clinical examination revealed that these five horses (group 1) had fever,
      anorexia, weakness and severe icterus and, in two mares, haemoglobinuria.
      Haematological examination revealed that all five horses were heavily parasitized
      with Babesia equi. This was also found in four horses (group 2) with no evidence
      of clinical babesiosis. In group 3 (94 horses), neither clinical signs nor B.
      equi were observed in the blood. The horses in group 1 and 2 recovered after
      treatment with imidocarb. When the mean values of white blood cell count, red
      blood cell count, haemoglobin and packed cell volume in group 1 were compared
      with those for groups 2 and 3, a significant difference was found (P < 0.05). A
      significant difference was also found when the mean values were compared before
      and after treatment. Examination of serum total protein, bilirubin and serum
      enzymes revealed a significant decrease in the mean value of total serum protein
      (P < 0.05), and a significant increase in the mean values of bilirubin (P < 0.05)
      in group 1 compared to groups 2 and 3. A significant elevation in the mean value
      of aspartate aminotransaminase, gamma-glutamyltransferase and creatine
      phosphokinase and a substantial elevation in the mean value of alkaline
      phosphatase was also observed in group 1 compared to groups 2 and 3. Postmortem
      examination of the dead horses showed that the animals had icterus, hepatomegaly
      and full urinary bladder with deep-red urine. Histopathological examination of
      the liver showed massive centrilobular degeneration and necrosis. The bile
      canaliculi and bile ducts were prominent and plugged with dark-brown to canary
      coloured bile pigments. The lungs had congestion, oedema, and thrombosis of
      pulmonary veins. Our results suggest that the horses suffered from B. equal with
      clinical manifestation following exercise. The clinical, haematological and
      pathological findings indicate that the animals suffered from haemolytic anaemia
      which responded to imidocarb therapy.

PMID- 9187025
TI  - The indirect fluorescent antibody test based on schizont antigen for study of the
      sheep parasite Theileria lestoquardi.
AB  - An indirect fluorescent antibody test (IFAT), based on schizont-infected
      lymphoblastoid cells, was applied to study the course of antibody production in
      adult sheep inoculated with attenuated, in vitro grown, Theileria lestoquardi
      (Theileria hirci) infected cells. Bright fluorescence of the intracellular
      schizonts could first be demonstrated 15 days after inoculation. A 32-64-fold
      rise in antibody titres was recorded 1 month after infection, and substantial
      titres were still observed 90 days after inoculation. Fluorescence was absent
      with negative control sera and background staining was minimal. No serological
      cross-reactions were detected with sheep sera positive for Babesia motasi,
      Babesia ovis or Toxoplasma gondii. Results obtained did not differ when antigens
      prepared from three different strains of T. lestoquardi infected lymphoid cells
      were compared. Testing for reactivity to non-pathogenic Theileria species of
      sheep revealed a low degree of cross-reaction of a Theileria ovis and a Theileria
      separata antiserum to T. lestoquardi antigen. Cross-reactions were also observed
      with bovine sera positive for Theileria annulata and Theileria parva. Moreover,
      T. lestoquardi positive sera reacted almost equally strongly with bovine T.
      annulata antigen as with their homologous antigen, whereas cross-reaction with
      bovine T. parva antigen was less pronounced. These results indicate a close
      antigenic relationship between ovine T. lestoquardi and T. annulata of cattle.

PMID- 9187026
TI  - Studies of resistance to anticoccidials in Eimeria field isolates and pure
      Eimeria strains.
AB  - Ten Eimeria field isolates from North Germany were studied in battery tests for
      sensitivity to selected anticoccidials. A high percentage of the Eimeria field
      isolates (9 out of 10) showed resistance to anticoccidials, mostly multiple
      resistance. Partial or complete resistance to maduramicin was found in 7 field
      isolates, to monensin in 6, to salinomycin in 5, to nicarbazin in 8, to
      halofuginone in 7, to robenidine and toltrazuril in 1, and to diclazuril in 2
      field isolates. Multiple resistance had developed in 7 of the 10 isolates. Cross
      resistance between maduramicin, monensin, and salinomycin occurred in 5 Eimeria
      isolates. One isolate showed cross-resistance between diclazuril and toltrazuril.
      From the resistant isolates 15 pure E. acerculina and 5 pure E. brunetti strains
      were obtained by single oocyst infections. Seven of the E. acerculina and 4 of
      the E. brunetti strains showed resistance or partial resistance that was also
      present in the original isolate. Ten of 11 resistant strains were multiply
      resistant.

PMID- 9187027
TI  - Evaluation of decoquinate to treat experimental cryptosporidiosis in kids.
AB  - The purpose of this trial was to evaluate the effects of decoquinate at 2.5
      mg/kg/day for 21 days to prevent an experimental cryptosporidiosis in kids.
      Twenty 1-day-old male kids (French Alpin), fed initially goat colostrum heated 1
      h at 56 degrees C and fed twice daily with nonmedicated milk replacer, were
      assigned into 2 groups. Kids of both groups were orally inoculated with 10(6)
      Cryptosporidium parvum (D0 = inoculation day). Group A kids were kept as
      nonmedicated controls and group B kids were orally medicated with 2.5 mg/kg/day
      of decoquinate (Deccox L. Rhone Poulenc Animal Nutrition) for 21 days from D-3 to
      D17. The studied criteria were body weight gain, oocyst shedding and specific
      anti-C. parvum immune response. In group A, the inoculation was not followed by
      mortality; but only by diarrhea and high oocyst shedding. Decoquinate reduced the
      severity of cryptosporidiosis in group B kids. The treatment prevented episodes
      of diarrhea and weight gain decrease for the D0-D7 and D0-D14 disease periods but
      did not allow a better final weight gain. The oocyst shedding was decreased in
      number and in duration. This parasitic development has induced a specific anti-C.
      parvum immune response. This drug is well-tolerated by animals and may be
      recommended in the prevention of ruminant cryptosporidiosis, a disease which has
      very limited treatment options.

PMID- 9187028
TI  - Anti-fecundity immunity to Schistosoma japonicum induced in Chinese water
      buffaloes (Bos buffelus) after vaccination with recombinant 26 kDa glutathione-S
      transferase (reSjc26GST).
AB  - We have shown previously that immunisation of mice and pigs with recombinant 26
      kDa GST (reSjc26GST) induces a pronounced anti-fecundity effect after
      experimental infection with Chinese Schistosoma japonicum. We report here that
      anti-fecundity immunity can also be induced against reSjc26GST in Chinese water
      buffaloes (Bos buffelus), important reservoir hosts for S. japonicum in China.
      Anti-Sjc26GST antibodies were produced in immunised buffaloes and, following
      challenge with S. japonicum cercariae, a 22.3% reduction in worm numbers was
      evident in vaccinated when compared with control animals. The anti-fecundity
      effect was characterised by a significant decrease in faecal egg output and eggs
      deposited in host tissues with those in the liver and intestine being reduced by
      about 50%. In addition to the anti-fecundity effect, reSjc26GST reduced by nearly
      40% the egg-hatching capacity of S. japonicum eggs into viable miracidia. In
      terms of vaccination strategy, these effects would combine to diminish pathology
      in animals immunised with reSjc26GST and reduce transmission of schistosomiasis
      japonica.

PMID- 9187029
TI  - Evaluation of various diagnostic techniques for Trypanosoma evansi infections in
      naturally infected camels.
AB  - One hundred and eight camels (Camelus dromedarius) from Trypanosoma evansi
      endemic areas of the Thar Desert of Rajasthan State, India, were evaluated by
      various diagnostic tests including parasitological tests (wet blood film-WBF,
      stained thick blood film), chemical test (mercuric chloride), biological test
      (mouse subinoculation-MSI), and immunodiagnostic tests based on antibody
      detection (double immunodiffusion test-DID, card agglutination test-CATT),
      antigen detection (double antibody sandwich enzyme linked immunosorbent assay-Ag
      ELISA). Of the tested camels 49 were found infected using the WBF of which nine
      gave false negative results with the mercuric chloride test. The efficacy of MSI
      was 87.03 percent, while the mercuric chloride test was 60.18 percent efficient.
      The diagnostic efficacy of CATT (72.22 percent) was found to be much better than
      DID (28.70 percent). Ag-ELISA was 86.11 percent efficient in detecting
      trypanosomal antigens. A good correlation was found between the positive results
      obtained by wet blood film, CATT and Ag-ELISA. It was inferred that CATT can be
      used to study the seroprevalence of T. evansi with great ease, however,
      trypanosome antigen detection may give a more accurate idea of the prevalence of
      T. evansi in an endemic area.

PMID- 9187030
TI  - Field trial for reducing porcine Taenia solium cysticercosis in Mexico by
      systematic vaccination of pigs.
AB  - It has previously been demonstrated that immunization of pigs with a crude
      extract of Taenia solium metacestodes can confer a high level of protection
      against an egg challenge. Furthermore, vaccination of infected animals also
      induces an immune response against the larvae, which are either destroyed or
      rendered non-infectious. To assess the efficacy of immunization as a strategy for
      reducing the prevalence of porcine cysticercosis, a field trial of this vaccine
      was performed in an endemic area in the northern region of the Guerrero State,
      Mexico, Random samples of pigs belonging to 17 villages were examined for
      metacestodes by inspection of their tongues. Each animal was immunized with a
      dose of 150 micrograms of protein (antigenic extract from Taenia solium
      metacestodes) by the intramuscular route. A prevalence of 2.4% of porcine
      cysticercosis on average was found in these villages at the beginning of the
      trial (62 cysticercotic pigs out of 2650 inspected). Six of these villages were
      selected for the periodic vaccination of new random samples of pigs. A
      statistically significant decline in the prevalence of porcine cysticercosis was
      observed at the end of the trial, decreasing from 2.4% at the beginning of
      vaccination to 0.45% at the end of the trial. A reduction of 82% was observed in
      spite of the poor living conditions in these villages. These results are
      consistent with previous data and suggest that it may be possible to turn a
      susceptible pig population into a protected one by systematic vaccination.

PMID- 9187031
TI  - Epidemiological observations on gastrointestinal nematode infections in grazing
      cow-calf pairs in Belgium.
AB  - The epidemiology of gastrointestinal helminth infections in beef cows and calves
      on pasture was studied in Belgium during the 1990 and 1992 grazing seasons.
      Weight gain, faecal egg counts, generic differentiation of infective larvae,
      serum pepsinogen levels, herbage larval counts and worm burdens of tracer calves
      were used as parameters. In Study 1 two groups of ten cows with their spring-born
      calves grazing on separate pastures (A and B) were monitored during the 1990
      grazing season. Ostertagia ostertagi was the predominant species shed by cows and
      calves. Cows on Pasture A had significantly higher egg counts at turn-out than
      the B cows, creating a high pasture contamination in the autumn, evidenced by
      high Ostertagia worm burdens in the Pasture A tracer calves. Calves of both
      groups showed low egg counts (mean < 60 eggs g-1 faeces, EPG) throughout the
      grazing season. In Study 2 nine cow-calf pairs were monitored during the 1992
      grazing season. The calves were born in winter or spring. Faecal egg counts of
      the cows remained low throughout the trial period. During the grazing season high
      egg counts were observed in the calves (mean up to 778 EPG). Cooperia oncophora
      was the predominant species in the calves. In the cows O. ostertagi,
      Oesophagostomum, C. oncophora and Trichostrongylus axei were present. It is
      suggested that, in the first study, the cows were the major source of pasture
      contamination, while in the second study the winter-born calves, being older and
      having a higher herbage intake resulting in a higher infection level, were
      largely responsible for the high Cooperia pasture infection level at housing.

PMID- 9187032
TI  - The in vitro uptake and incorporation of hemoglobin by adult Haemonchus
      contortus.
AB  - The incorporation of radioactivity from [3H]leucine-labeled hemoglobin (Hb) into
      adult Haemonchus contortus proteins was investigated. Further, the role of
      previously described cysteine proteases present in intestinal tissue and
      excretory/secretory products of H. contortus was assessed in the breakdown of Hb.
      A cell lysate preparation (predominantly Hb) was obtained from reticulocytes
      metabolically labeled, in vitro, with [3H]leucine. Following 24-h incubation in
      the presence of [3H]Hb, adult H. contortus incorporated radioactivity. The
      presence of the protein synthesis inhibitor puromycin (200 micrograms ml-1)
      reduced incorporation by 72%, indicating that this process was dependent on
      protein synthesis. The specific cysteine protease inhibitor Z-phe-ala-FMK (PAF)
      at 0.1 mM had no effect on incorporation of radioactivity; however, the breakdown
      of Hbg in the culture medium was reduced by 50%. In contrast, PAF at 1.0 mM
      caused a 78% reduction in incorporated radioactivity. Parasite viability was also
      decreased by 1.0 mM PAF, and thus the reduction of incorporation of radioactivity
      may not be due to specific enzyme inhibition. The serine protease inhibitor 4-(2
      aminoethyl)benzenesulfonyl fluoride (AEBSF) at 1.0 mM caused a 40% reduction in
      incorporation of radioactivity; the aspartic protease inhibitor pepstatin (1 mM)
      was without effect. Adult H. contortus also incorporated radioactivity from
      [3H]leucine-labeled intact reticulocytes. This incorporation was inhibited-by 1.0
      mM PAF and AEBSF in a manner similar to that for the cell lysate preparation.
      These data indicate that adult H. contortus degrade Hbg and incorporate the
      radioactivity into their macromolecules. The specific action of the endogenous
      cysteine protease in the digestion of Hbg could not be demonstrated
      unequivocally. However, the hypothesis that the secreted cysteine protease
      functions in extracorporeal digestion was supported.

PMID- 9187033
TI  - The sensitivity of the Baermann method for the diagnosis of primary Dictyocaulus
      viviparus infections in calves.
AB  - Data from calves infected experimentally with 20 larvae of Dictyocaulus viviparus
      demonstrate that the Baermann method, using 30 g of faeces per calf is extremely
      sensitive for diagnosis of patent infections in young cattle. Between 5 and 7
      weeks after primary infection it is sensitive enough to diagnose the presence of
      one patent female worm.

PMID- 9187034
TI  - Effect of simulated rain, coat length and exposure to natural climatic conditions
      on the efficacy of a topical formulation of eprinomectin against endoparasites of
      cattle.
AB  - A series of five controlled studies involving 114 cattle were conducted in
      Australia, North America and the United Kingdom to examine the effect of
      simulated rain, coat length and exposure to natural climatic conditions, on the
      efficacy of a topical formulation of eprinomectin against nematode parasites of
      cattle. In all trials infections were induced with a range of bovine nematode
      species and treatment was applied when the majority of nematodes were mature. In
      one study, simulated rain was applied to cattle ending one hour before treatment
      or beginning one, three or six hours after treatment. In a second study cattle
      had short (1 cm) or long (3-6 cm) haircoats at the time of treatment. Three other
      studies were conducted using cattle housed indoors or exposed to various natural
      climatic conditions. Nematode counts were determined using standard techniques
      and the efficacy of treatment was assessed relative to vehicle-treated controls.
      Regardless of the timing of simulated rain relative to treatment, eprinomectin
      was at least 99.9% effective (P < 0.01) against Haemonchus placei, Ostertagia
      ostertagi. Trichostrongylus axei and Cooperia spp. There were also no differences
      (p > 0.10) in efficacy between treatment administered to dry or wet cattle, or
      treatment administered before or after simulated rainfall. Efficacies against O.
      ostertagi, T. axei, Cooperia ancophora and Dictyocaulus viviparus were > 99.5% (p
      < 0.01) regardless of the length of the haircoat at the application site.
      Exposure of treated cattle to sunshine and precipitation had no effect on
      anthelmintic efficacy (p > 0.10) with efficacies of greater than 99.5% being
      maintained against H. placei, O. ostertagi (adult and fourth-stage larvae), T.
      axei, Cooperia spp., Nematodirus helvetianus (adult and inhibited fourth-stage
      larvae) and Oesophagostomum radiatum. These findings indicate that eprinomectin
      (500 micrograms/kg) in a topical formulation is a safe and highly effective
      nematocide for cattle regardless of their coat length and this high level of
      efficacy is maintained in cattle exposed to a wide variety of climatic
      conditions.

PMID- 9187035
TI  - Gastrointestinal nematode infections of first-season grazing calves in Belgium:
      general patterns and the effect of chemoprophylaxis.
AB  - Comparative analyses of the patterns of gastrointestinal nematode infections of
      first-grazing season cattle in Belgium are presented. The analysis involves 17
      studies covering a 10 year period on 13 different farms in Flanders, Belgium. In
      all studies the calves were divided into an untreated control group, and one or
      two groups treated with chemoprophylactic systems. Two general infection levels
      emerged-'sub-clinical' (14 studies) and 'clinical' (three studies). The 'sub
      clinical' infections were characterised by no clinical signs of parasitic
      gastroenteritis in the untreated control groups. Mean faecal egg counts remained
      low (less than 200), maximum pepsinogen levels only reached about 3500 mU
      tyrosine, and very small reductions in overall daily weight gain were observed
      compared with calves given chemoprophylaxis (less than 40 g day-1). Based on
      these results, on these 'sub-clinical' farms, chemoprophylaxis may not have been
      needed. In contrast, multiple salvage treatments of the control calf groups were
      required in the 'clinical' infections. Even with these salvage treatments mean
      faecal egg counts were high (more than 300), maximum pepsinogen levels were over
      5500 mU tyrosine and there was a very large reduction in overall daily weight
      gain (more than 300 g day-1). However, it was not possible to predict either at
      turnout, or during the first month afterwards whether an infection on a
      particular farm would develop into a 'clinical' infestation. With the present
      data this prediction was possible from 8 weeks (Day 56) onwards, based on faecal
      egg counts and pasture larval contamination. It was also possible to predict
      using serum pepsinogen levels on Day 84. Therefore, one possible strategy for the
      effective control of gastrointestinal nematode infections of calves in temperate
      regions would be to evaluate faecal egg counts 2 months after turnout, and then
      only start treatment (i.e. metaphylaxis) if required.

PMID- 9187036
TI  - Evaluation of an enzyme-linked immunosorbent assay (ELISA) for the serological
      diagnosis of sarcoptic mange in swine.
AB  - An enzyme-linked immunosorbent assay (ELISA) using an extract from Sarcoptes
      scabiei var. culpes as antigen was evaluated for its usefulness in monitoring
      antibodies to S. scabiei var. suis in naturally infected pigs. Five hundred and
      fifty-eight serum samples from certified Sarcoptes-free pigs (120 from weaned
      piglets, 218 from fatteners and 220 from adult sows) and 94 samples from
      certified Sarcoptes-infected pigs (35 from weaned piglets, 45 from fatteners and
      14 from adult sows) were examined. The cut-off optical density (OD) values,
      considered to reflect the presence of antibodies to S. scabiei var. suis, were
      determined to be 0.059, 0.213 and 0.374 for weaners, fatteners and sows,
      respectively. The specificity of the ELISA was high (> or = 98%) for all age
      groups. Sensitivity was highest in the piglets (80%), followed by fatteners (78%)
      and sows (50%). These results indicate that an ELISA may be a simple and valuable
      alternative to monitor S. seabiei var. suis infections in naturally infected
      weaners and fatteners.

PMID- 9187037
TI  - Treatment and prophylaxis of psoroptic mange of sheep by a 10% w/w dip
      formulation of high CIS-cypermethrin.
AB  - A 10% w/w dip formulation of high CIS-cypermethrin (Ecofleece sheep dip) was
      evaluated as a prophylactic and treatment method against Psoroptes ovis of sheep.
      A laboratory trial using groups of healthy sheep under challenge showed that,
      when dipped as directed for 1 min, they were protected against infection for at
      least 4 weeks. Twelve sheep infected with psoroptic mange at the laboratory were
      effectively treated by one dipping in Ecofleece. A field outbreak of psoroptic
      mange in a flock of 237 crossbred ewes was likewise successfully treated by just
      one dipping. As this formulation is also effective against blowfly myiasis it is
      a useful alternative to organophosphate dual purpose dips.

PMID- 9187038
TI  - Wound myiasis of sheep in Hungary.
AB  - In Hungary, 4388 sheep in six flocks were surveyed in June-August of 1992-1995 to
      gather basic data on wound myiasis, its incidence, the predominant fly species
      involved and the clinical manifestations of infestation. The pathogenesis and
      economic significance of wound myiasis, as well as the interrelation of breed and
      sex with infestation levels, were evaluated. Active wound myiasis was recorded in
      all flocks, in 17.6% (774/4388) of the inspected sheep. The incidence varied
      among flocks and inspections from 4.7% to 38.9%, but it was significantly greater
      in imported breeds (28.8%, 651/2257) than in indigenous breeds (5.8%, 123/2131).
      Lesions of wound myiasis were located more frequently on the external genital
      organs (in 87%, 673/774 of all cases) than on other body regions. Overall,
      significantly more males (74.3%, 61/82) than females (16.5%, 713/4306) were
      infested. With the exception of five cases (0.06% of the total), when larvae of
      Lucilia sericata (Diptera: Calliphoridae) were also found, Wohlfahrtia magnifica
      (Diptera: Sarcophagidae) was the only species identified in wounds in this study.
      Despite the fact that larvae of L. sericata were so rarely encountered in wounds,
      adults of L. sericata were much the more common of the two species observed
      around wounds, even those infested by W. magnifica. The vast majority of animals
      inspected had only one myiasis wound. Clinical signs depended on the body part
      affected. The most severe infestations, in terms of extent of wounds and numbers
      of visible larvae, were usually those of the vulva and prepuce. Wound consisted
      of from one up to six foci, each completely filled by larvae of W. magnifica.
      These foci were either isolated from each other or they merged into a large
      lesion. Larvae in any focus tended to be at the same stage of development, but,
      were wounds were very severe, a range of developmental stages was observed
      together, indicating that frequent restrikes of wounds occurred. The most common
      signs were restlessness, anxiety and reluctance to graze. The animals were
      obviously depressed when they suffered from severe infestations causing lameness
      or blindness. Some of the most severely affected animals displayed obvious loss
      of condition. However, overall, there was no significant difference between the
      mean bodyweights of a sample of infested (59.2 kg) and uninfested (60.9 kg)
      animals.

PMID- 9187039
TI  - A novel dip formulation of a synthetic pyrethroid (SP) for the control of blowfly
      myiasis of sheep.
AB  - Field trials were carried out during the summer months of 1994 and 1995 to
      ascertain the prophylactic effects of a 10% w/w formulation of a synthetic
      pyrethroid (Ecofleece, Cross Vetpharm Group Ltd.) against sheep blowfly myiasis
      (fly strike). The trials were carried out on the same three farms each year. The
      flocks, of mixed breeds, comprised between 500 and 700 sheep. Treated sheep which
      consisted of ewes and lambs were plunge dipped, with at least one complete
      immersion. At least 10% of each flock were left untreated to act as sentinels.
      Both sentinel and treated sheep mixed freely at pasture. All recorded cases of
      fly myiasis were treated by topical applications of the same formulation.
      Inspections of the flocks were made daily by the farmers and weekly by one of the
      investigators. Prophylaxis against blowfly myiasis was achieved for periods
      ranging from 3 to 9 weeks. On some occasions, fly larvae developed in faecal dags
      but failed to establish on the sheep or cause lesions.

PMID- 9187040
TI  - Artificially induced Trypanosoma brucei brucei infection in Lagune and Borgou
      cattle in Benin.
AB  - Lagune (n = 10) and Borgou (n = 10) cattle of Benin were inoculated
      subcutaneously with Trypanosoma brucei brucei AnTat, 1.1E. Clinical signs, packed
      cell volume (PCV), parasitaemia, specific trypanolytic antibodies and haemolytic
      complement were monitored to evaluate the between-and-within breed variations.
      All the animals showed only transitory symptoms with clinical recovery within 20
      days post infection. Infected animals showed a moderate drop in PCV after 5-10
      days of infection. The drop in PCV at day 20 was 2.9 +/- 2.7% for Borgou and 1.2
      +/- 1.8% for Lagune. Except two animals of Borgou breed, all animals developed
      detectable parasitaemia. Two peaks of parasitaemia, the first on day 5-6 and the
      second on day 9-10 post infection, were observed. Parasitaemia persisted for 25
      days in two Borgou and one Lagune cattle. There were large individual variations
      in PCV and parasitaemia. AnTat 1.1 specific trypanolytic antibodies were detected
      from day 6-7 in all animals, except one Borgou and they persisted until the end
      of observation on day 30. A drop in serum haemolytic complement occurred
      corresponding to the first parasitaemic waves. After day 15, complement level was
      restored rapidly largely exceeding the initial values of day 0. The results
      indicate that all the artificially infected individuals belonging to the Borgou
      breed as well as to the better known Lagune breed are tolerant to Trypanosoma
      brucei brucei infection.

PMID- 9187041
TI  - Occupational medicine at the verge of the twenty first century: evaluation of
      accomplished and expected changes in the preventive approach.
AB  - The World Bank in its document under the title 'Investing in Health' (1993)
      states that the health status of the population, including the working
      population, and working conditions in individual countries depend essentially on
      the value of gross national product per capita. The attitudes towards the role
      and objectives of occupational medicine have changed significantly over the last
      three decades. A high priority given to primary prevention reflects the
      mainstream of a new approach to preventive measures. Advancements in technology,
      production and services, common use of computers and flattening of work
      organisation structures have brought about the need for workers' active
      participation in planning of activities and shaping working conditions in own
      enterprise. At the same time, workers are required to possess much higher
      qualifications facilitating their participation in applying new technologies and
      using new information systems, which resulted in a fierce competition on the
      labour market. In the countries in the political, social and economic transition,
      the conditions for introducing a new system of sustained development, described
      by Gustavsen at the 25th International Congress on Occupational Health have not
      as yet been established. A procedure-based system involving negotiations between
      employers and workers' representatives failed to be successful in improving
      working conditions as the roles of the state, employers and trade unions had not
      been defined precisely. It is expected that further health promotion at the
      worksites in these countries will depend mainly on the economic progress and the
      reformed system of education.

PMID- 9187042
TI  - Kienbock's disease. I. Anatomy and Etiology.
AB  - Cumulative trauma disorders (CTD) pose a major industrial problem in terms of
      increased medical costs, lost productivity and degraded worker health and safety.
      From an anatomical view, CTD's are classified into three major categories: tendon
      disorders, neurovascular disorders and nerve disorders. Up until recently these
      categories seemed to cover CTD of the upper extremity, however, Kienbock's
      disease, a typically less common disease and one that does not fit into the
      established CTD categories, has been observed to exhibit CTD characteristics and
      does appear in the manufacturing environment. The most common types of employment
      observed to exhibit individuals with this disease are carpentry, jobs involving
      the use of pneumatic tools (wrench), spot welders, sheet metal work, farmers and
      factory workers. The present article makes a critical examination of the relevant
      anatomy and etiologic aspects of this disease.

PMID- 9187043
TI  - Cancer mortality among pulp and paper workers in Poland. A cohort study.
AB  - Mortality among workers in the Polish pulp and paper industry was evaluated in a
      cohort study of 10,460 workers who had been employed continuously for at least
      one year, between 1968 and 1990 in the factory producing sulphate pulp, paper,
      board and paper products. Three subcohorts were formed according to the work
      areas. A standardized mortality ratio (SMR) analysis was used to compare death
      rates for each group exposed with Polish national rates. Mortality from all
      causes and from all malignant neoplasms, both in the female and in male cohorts
      was lower than that observed in the general population. In the pulp male
      subcohort a significantly elevated risk of death from peritoneum cancer (2 obs,
      SMR = 2,530) and prostate cancer (4 obs, SMR = 854) was recorded, although
      overall mortality from all causes and from all malignant neoplasms was lower than
      expected. The excess of deaths from neoplasms in other sites was statistically
      nonsignificant in all subcohorts. This study did not confirm the excess mortality
      from lung, stomach and lymphatic cancers found by other authors. The "young"
      cohort and a relatively short follow-up period (23 years) might have affected the
      results.

PMID- 9187044
TI  - Occupational respiratory diseases in laboratory animal workers: initial results.
AB  - Laboratory-animal allergy (LAA) is a well-known occupational hazard to workers
      employed in biological or medical research institutes and in the pharmaceutical
      industry. The aim of this study was to focus on the problem of LAA and to assess
      factors predisposing to sensitization among subjects occupationally exposed to
      animals. Sixty workers were examined in our study. They responded to a
      questionnaire and underwent spirometry (Vital Capacity, VC and Forced Expiratory
      Volume in one second, FEV1). In addition, Peak Expiratory Flow (PEF) and the
      histamine provocation test were estimated in 5 subjects that had been
      hospitalized in the Department of Occupational Diseases. Skin prick tests with
      common allergens and with hair extracts from laboratory animals were performed,
      and total IgE levels and specific IgE antibodies were also measured. Among 60
      subjects who had been working with animals, 26 had positive skin prick tests for
      one or more of the common allergens. Five subjects supposed to have occupational
      bronchial asthma and four with occupational allergic rhinitis showed positive
      skin prick tests for one or more animal allergens, increased total IgE levels and
      specific serum IgE antibodies. All these subjects had smoked for years.
      CONCLUSIONS: 1) Laboratory animal allergy develops within first years of
      exposure; 2) atopy and smoking predispose to laboratory animal sensitization and
      to a development of bronchial asthma and allergic rhinitis.

PMID- 9187046
TI  - Can we detect mutagenic activity of urinary sediment by the Ames test?
AB  - Using the Salmonella typhimurium strain TA98 we tested the mutagenicity of
      filtrate and sediment of urine collected from children and coke-oven workers
      living in the town of Dabrowa Gornicza. Mutagenic substances were detected in
      samples of urinary filtrate taken either from environmentally exposed children or
      from occupationally exposed coke-oven workers. The mutagenic effect was found
      only in acetone extracts of urinary filtrate in the presence of promutagenic
      activating fraction S9. Beta-glucuronidase/arylsulphatase treatment hydrolysed
      the conjugates contained urinary filtrate into compounds that were toxic towards
      tester strain. The mutagenic effect of urine should be tested only in urinary
      filtrate as we have never detected mutagenic substances in urinary sediment.

PMID- 9187045
TI  - Impairment of psychological functions in children environmentally exposed to
      lead.
AB  - The major objective of the study was to determine whether environmental exposure
      to lead exerts a negative impact upon psychological functions in children. The
      examined group consisted fo school age children (6-15 years old, x = 9.5, SD =
      1.4) living close to copper works. Out of 4548 children with measured blood lead
      concentrations, two groups were selected one with the highest exposure levels
      (12.0-27.2 micrograms/dl) and the other drawn from the remaining children, with
      low blood lead levels. The mean exposure level for the whole examined group
      equalled 10.18 mu/dl PbB (SD-4.73 micrograms/dl). To assess effects of the
      exposure, the following variables were measured in the examined children:
      intelligence, hand-eye coordination, perception, memory, reaction time and
      accuracy, and behaviour disorders. The moderator variables of sociodemographic
      character, i.e. parents' education, income, etc., were also controlled. A
      significant impact of lead upon psychological functions and behaviour was
      revealed for two variables only: intelligence and attention concentration. An
      increase in the exposure level by 10 micrograms/dl PbB was associated with
      deterioration of general IQ by 5.3 points and growth of the number of mistakes in
      the Simple Reaction Time test by 3.3. It was also revealed that the short-term
      memory deteriorates with growing level of exposure, the strength of this
      relationship was close to the level of statistical significance (p < 0.07).

PMID- 9187047
TI  - Mutagenic and genotoxic activity detected by the Ames, micronucleus and SCE tests
      under the influence of samples of dyes manufactured in Poland.
AB  - In this study, we evaluated the mutagenic and genotoxic potential of commercial
      samples of chemicals manufactured by Polish dyestuff industry for their ability
      to mutate Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102), and to
      induce formation of micronuclei (MN) and sister chromatid exchanges (SCE) in mice
      bone marrow cells. This study involved five dyes selected from a list of
      colorants, considered to be representative of those which were most extensively
      used in the trade. According to criteria listed by IARC (1984), the results
      obtained in this work and earlier tests of Basic Blue 26, 44045 and Direct Red
      83, 29225 provided no evidence of genetic activity (all 3 tests were negative);
      for Acid Violet 49, 42640 and Disperse Blue 37, the evidence of genetic activity
      was inadequate (1 test was positive) and the tests for Acid Black 194 provided
      limited evidence of genetic activity (2 positive tests).

PMID- 9187048
TI  - Effect of angiotensin II on the reactivity of isolated mesenteric vessels to
      norepinephrine in rats poisoned with cadmium.
AB  - This study was designed to investigate the effect of cadmium on vascular response
      to norepinephrine (NE) administered before and during infusion of angiotensin II.
      The experiments were performed on isolated mesenteric vessels obtained from rats
      administered cadmium chloride intragastrically in doses of 20 mg Cd/kg body wt.
      once a week for 7 weeks. Changes in mesenteric vascular resistance due to NE were
      measured in the constant flow system as an increase in perfusion pressure. There
      was significant difference in the 50% effective doses (ED50) for NE between the
      two groups of rats when the dose-response curves were normalized to their
      respective maximal responses: ED50 NE for cadmium-exposed rats was lower and the
      dose-response curve was shifted to the left. Another change indicating an
      increased vasoconstrictor action of NE due to cadmium is more effective
      potentiation of exogenous NE responses produced by angiotensin II infused in dose
      of 5 mg/ml. In contrast to the controls in cadmium poisoned rats, propranolol in
      a dose of 300 ng/ml did not change significantly the vasoconstrictor response to
      NE and diminished the difference between angiotensin effect in vessels.
      Nifedipine (100 ng/ml), infused together with angiotensin II, inhibited pressor
      response to norepinephrine in preparation from both control and cadmium treated
      rats, to 60.5% and 69.3%, respectively. These results suggest an increase in the
      postsynaptic alpha adrenergic response and show a stronger potentiation of
      exogenous NE responses produced by angiotensin II, probably due to its influence
      on the calcium homeostasis in vessels of cadmium poisoned rats.

PMID- 9187049
TI  - Occupational exposure in Polish paint and lacquer industry.
AB  - Evaluation of occupational exposure to solvent vapours in the production of
      paints and lacquers is presented. The measurements were carried out in 5 paint
      and lacquer producing plants of the varied level of technical and technological
      advancement. Evaluation of exposure was based on determination of all substances
      identified in the work environment. Analysis was performed by gas chromatography
      with MSD and FID. Standard mixtures composed of 40 substances were used for
      calibration. The determined levels of exposure were directly dependent on
      technical conditions and modernisation status in factories investigated.
      Measurements were carried out in the uniform analytical system, which assures
      comparability of the data from all the factories under study.

PMID- 9187050
TI  - Developmental genome reorganization in ciliated protozoa: the transposon link.

PMID- 9187051
TI  - DNA excision repair assays.

PMID- 9187052
TI  - The mitochondrial uncoupling protein: structural and genetic studies.

PMID- 9187053
TI  - Molecular regulation of cytokine gene expression: interferon-gamma as a model
      system.
AB  - The regulation of IFN-gamma transcription appears to be quite complex. In
      addition to the interaction of numerous regions of the genomic DNA with multiple
      DNA binding protein family members, DNA methylation may serve to act as an early
      determinant of the capacity of a cell to initiate transcription. Transcriptional
      activation occurs in response to both soluble extracellular signals and cell
      contact, and it appears quite likely that this activation may result from the
      interaction of different families of DNA binding proteins with different enhancer
      elements. Furthermore, because chronic IFN-gamma transcription and subsequent
      expression would likely be detrimental to the host (see 81), mechanisms have
      evolved to quench expression at both transcriptional and posttranscriptional
      levels. Given the complexity of cell-to cell interactions in the immune system,
      it is reasonable to expect that additional mechanisms regulating IFN-gamma
      transcription, involving previously identified or as yet unidentified DNA binding
      proteins, remain to be defined.

PMID- 9187054
TI  - RecA protein: structure, function, and role in recombinational DNA repair.

PMID- 9187055
TI  - Molecular biology of axon-glia interactions in the peripheral nervous system.

PMID- 9187056
TI  - Regulation of eukaryotic messenger RNA turnover.
AB  - We have demonstrated the existence of multiple mRNA binding proteins that
      interact specifically with defined regions in posttranscriptionally regulated
      mRNAs. These domains appear to be destabilizers whose function can be attenuated
      by the interaction with the specific binding proteins. Thus, the ability to alter
      mRNA decay rates on demand, given different environmental or intracellular
      conditions, appears to be mediated by controlling the localization, activity, and
      overall function of the cognate binding protein. Based on our limited experience,
      we predict that most, if not all, of similarly regulated mRNAs will ultimately be
      found to interact with regulatory mRNA binding proteins. Under conditions whereby
      the mRNA binding proteins are constitutively active (e.g., tumor cell lines),
      abnormal mRNA decay will result, with accumulation and overtranslation. Such
      appears to be the case for cytokines and possibly amyloid protein precursor mRNAs
      in cancer and Alzheimer's disease, respectively. Conversely, mutagenesis of these
      critical 3' untranslated region elements will likely have comparable deleterious
      effects on the regulation of gene expression. To the extent that such
      derangements exist in human disease, attention to understanding the mechanistic
      detail at this level may provide insights into the development of appropriate
      therapeutics or treatment strategies.

PMID- 9187057
TI  - New and atypical families of type I interferons in mammals: comparative
      functions, structures, and evolutionary relationships.

PMID- 9187058
TI  - General transcription factors for RNA polymerase II.

PMID- 9187059
TI  - Biochemistry and molecular genetics of cobalamin biosynthesis.

PMID- 9187060
TI  - Binding theory and grammatical specific language impairment in children.
AB  - This study investigates the intrasentential assignment of reference to pronouns
      (him, her) and anaphors (himself, herself) as characterized by Binding Theory in
      a subgroup of "Grammatical specifically language-impaired" (SLI) children. The
      study aims to (1) provide further insight into the underlying nature of
      Grammatical SLI in children and (2) elucidate the relationship between different
      sources of knowledge, that is, syntactic knowledge versus knowledge of lexical
      properties and pragmatic inference in the assignment of intrasentential
      coreference. In two experiments, using a picture-sentence pair judgement task,
      the children's knowledge of the lexical properties versus syntactic knowledge
      (Binding Principles A and B) in the assignment of reflexives and pronouns was
      investigated. The responses of 12 Grammatical SLI children (aged 9:3 to 12:10)
      and three language ability (LA) control groups of 12 children (aged 5:9 to 9:1)
      were compared. The results indicated that the SLI children and the LA controls
      may use a combination of conceptual-lexical and pragmatic knowledge (e.g.,
      semantic gender, reflexive marking of the predicate, and assignment of theta
      roles) to help assign reference to anaphors and pronouns. The LA controls also
      showed appropriate use of the syntactic knowledge. In contrast, the SLI children
      performed at chance when syntactic information was crucially required to rule out
      inappropriate coreference. The data are consistent with an impairment with the
      (innate) syntactic knowledge characterized by Binding Theory which underlies
      reference assignment to anaphors and pronouns. We conclude that the SLI
      children's syntactic representation is underspecified with respect to
      coindexation between constituents and the syntactic properties of pronouns.
      Support is provided for the proposal that Grammatical SLI children have a modular
      language deficit with syntactic dependent structural relationships between
      constituents, that is, a Representational Deficit with Dependent Relationships
      (RDDR). Further consideration of the linguistic characteristics of this deficit
      is made in relation to the hypothesized syntactic representations of young
      normally developing children.

PMID- 9187061
TI  - Explaining human movements and actions: children's understanding of the limits of
      psychological explanation.
AB  - Human actions and movements can be caused by psychological states (e.g. beliefs
      and desires), physical forces (e.g. gravity) and biological processes (e.g.
      reflexes). In three studies we explored young children's understanding of the
      causes of human movements in order to examine their ability to differentiate and
      coordinate psychological, physical and biological reasoning to account for the
      activities of one single entity--a human being. In Study 1, 4-year-olds explained
      characters' voluntary actions, mistakes, physically-caused and biologically
      caused behaviors and movements. Children gave psychological explanations for the
      intended actions and mistakes, but biological and physical explanations for the
      biologically-caused and physically-caused movements. Studies 2 and 3 extended the
      investigation to younger children (3-year-olds), encompassed a greater variety of
      items, and used several converging methods in order to examine children's
      judgments and explanations. Consistently, 3- and 4-year-olds gave appropriately
      different responses and explanations to the different item types. These findings
      show that far from viewing people in strictly psychological terms, young children
      evidence multiple causal-explanatory construals of human behavior. We discuss the
      implications of these findings for children's everyday psychological, physical,
      and biological theories. One implication of the findings is that young children
      do not assume a match between entities and theories (persons-psychology, objects
      physics). If they do not, this raises the question of what information they use
      to decide which explanatory system fits which events.

PMID- 9187062
TI  - Intuitive knowledge of linguistic co-reference.
AB  - The research reported here is a systematic investigation of what competent,
      native speakers of English, native to contemporary syntactic theory, judge to be
      grammatically acceptable patterns of co-reference involving names and pronouns.
      Its central goal is the specification of syntactic factors that influence co
      reference within and between sentences. The results show that naive subjects have
      consistent intuitions of grammaticality that agree with some principles of
      contemporary binding theory. The results also show that naive subjects diverge
      substantially from syntactic theorists in other judgments of grammaticality. In
      particular, subjects have strong intuitions that reflexives and pronouns are in
      complementary distribution, a fact that supports contemporary syntactic theory.
      Beyond that domain, subjects' judgments of co-reference in name-pronoun, name
      name, and pronoun-name sequences are systematically influenced by syntactic
      structure in ways that are not consistent with syntactic theory. Co-reference in
      name-pronoun sequences is generally quite acceptable but becomes more acceptable
      as the syntactic prominence of the name increases. Co-reference in name-name
      sequences is only moderately acceptable and becomes less acceptable as the
      syntactic prominence of the first name increases. Co-reference in pronoun-name
      sequences is generally unacceptable and is only weakly influenced by the kinds of
      syntactic prominence that affect other relations of co-reference. We account for
      these results through the elaboration of a model of the process by which
      syntactic representations are mapped onto a representation of discourse capable
      of expressing generalizations about co-reference both intra-sententially and
      inter-sententially.

PMID- 9187063
TI  - The effect of premise order in conditional reasoning: a test of the mental model
      theory.
AB  - The difference in difficulty between modus ponens (if p then q; p; therefore q)
      and modus tollens (if p then q; not-q; therefore not-p) arguments has been
      traditionally explained by assuming that the mind contains a rule for modus
      ponens, but not for modus tollens. According to the mental model theory, modus
      tollens is a more difficult deduction than modus ponens because people do not
      represent the case not-q in their initial model of the conditional. On the basis
      of this theory, we predicted that conditions in which reasoners are forced to
      represent the not-q case should improve correct performance on modus tollens. In
      particular, we predicted that the presentation of the minor premise (not-q) as
      the initial premise should produce facilitation. Experiment 1 showed that this is
      the case: whereas the inversion of the premise order did not affect modus ponens,
      it produced a significant increase of valid conclusions for modus tollens.
      Experiment 2 showed that this facilitation does not depend on the negative form
      (contrary vs. contradictory) of the minor premise. Experiments 3 and 4 (and/or
      some of their replications) demonstrated that facilitation also occurs when
      participants are asked to find the cases compatible with not-q or to evaluate a p
      conclusion. No premise order effect was found for sentences which make explicit
      the not-q case right from the start, i.e. p only if q conditionals and
      biconditionals (Experiments 5 and 6). Finally, Experiments 7 and 8 showed that
      the conditional fallacies are not significantly affected by the premise order.

PMID- 9187064
TI  - Salience of visual parts.
AB  - Many objects have component parts, and these parts often differ in their visual
      salience. In this paper we present a theory of part salience. The theory builds
      on the minima rule for defining part boundaries. According to this rule, human
      vision defines part boundaries at negative minima of curvature on silhouettes,
      and along negative minima of the principal curvatures on surfaces. We propose
      that the salience of a part depends on (at least) three factors: its size
      relative to the whole object, the degree to which it protrudes, and the strength
      of its boundaries. We present evidence that these factors influence visual
      processes which determine the choice of figure and ground. We give quantitative
      definitions for the factors, visual demonstrations of their effects, and results
      of psychophysical experiments.

PMID- 9187065
TI  - Identity and similarity factors in repetition blindness: implications for lexical
      processing.
AB  - The influence of identity and similarity of repeated items on repetition
      blindness (RB) was investigated in two rapid-serial-visual processing (RSVP)
      tasks. In Experiment 1, the difference between correct recall for sentences
      containing repeated identical items and their controls was contrasted with the
      difference between correct recall for sentences containing pairs of
      orthographically similar items (fish-dish) and their controls. In Experiment 2
      the same comparison was made between sentences containing repeated identical
      items and sentences containing pairs of orthographically identical items (the
      watch-to watch). The amount of RB elicited by the two conditions was measured at
      three different temporal lags. The results show that the function that describes
      performance over time for the repeated-identical (R-I) condition is different
      from that for the condition in which the items are orthographically similar
      (repeated-neighbor: R-N) or orthographically identical (repeated-homonym: R-H).
      The results are interpreted as suggesting that the decrements in performance
      observed for recall of the second occurrence of the repeated item in the R-I and
      the R-N and R-H conditions have different underlying causes.

PMID- 9187066
TI  - Postmenopausal hormone therapy and mortality.
AB  - BACKGROUND: Postmenopausal hormone therapy has both benefits and hazards,
      including decreased risks of osteoporosis and cardiovascular disease and an
      increased risk of breast cancer. METHODS: We examined the relation between the
      use of postmenopausal hormones and mortality among participants in the Nurses'
      Health Study, who were 30 to 55 years of age at base line in 1976. Data were
      collected by biennial questionnaires beginning in 1976 and continuing through
      1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was
      matched with 10 controls alive at the time of her death. For each death, we
      defined the subject's hormone status according to the last biennial questionnaire
      before her death or before the diagnosis of the fatal disease; this reduced bias
      caused by the discontinuation of hormone use between the time of diagnosis of a
      potentially fatal disease and death. RESULTS: After adjustment for confounding
      variables, current hormone users had a lower risk of death (relative risk, 0.63;
      95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken
      hormones; however, the apparent benefit decreased with long-term use (relative
      risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in
      mortality from breast cancer among long-term hormone users. Current hormone users
      with coronary risk factors (69 percent of the women) had the largest reduction in
      mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57),
      with substantially less benefit for those at low risk (13 percent of the women;
      relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). CONCLUSIONS:
      On average, mortality among women who use postmenopausal hormones is lower than
      among nonusers; however, the survival benefit diminishes with longer duration of
      use and is lower for women at low risk for coronary disease.

PMID- 9187067
TI  - Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile
      neutropenia.
AB  - BACKGROUND: Randomized trials of colony-stimulating factors in febrile patients
      with neutropenia after chemotherapy have not consistently shown clinical benefit.
      Nevertheless, the use of colony-stimulating factors to treat patients with
      chemotherapy-induced neutropenia is widespread. METHODS: We performed a
      randomized, double-blind, placebo-controlled trial of granulocyte colony
      stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy
      induced neutropenia. We measured the number of days of neutropenia, rate of
      hospitalization, number of days in the hospital, number of days the patient
      received parenteral antibiotics, and number of culture-positive infections.
      RESULTS: We randomly assigned 138 patients to receive G-CSF (n=71) or placebo
      (n=67). The median time to an absolute neutrophil count of at least 500 per cubic
      millimeter was significantly shorter for patients who received G-CSF (two days,
      vs. four days for the patients given placebo). However, there was no effect on
      the rate of hospitalization, number of days in the hospital, duration of
      treatment with parenteral antibiotics, or number of culture-positive infections.
      CONCLUSIONS: Routine therapeutic application of G-CSF in afebrile patients with
      severe neutropenia can reduce the duration of neutropenia, but this does not
      appear to provide practical clinical benefit.

PMID- 9187068
TI  - Human granulocyte colony-stimulating factor after induction chemotherapy in
      children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Recombinant human granulocyte colony-stimulating factor PO1 CA
      20180ilgrastim) hastens the recovery from neutropenia after P30 CA
      21765emotherapy, but its role in the management of childhood leukemia is unclear.
      METHODS: We randomly assigned 164 patients with acute lymphoblastic leukemia (age
      range, 2 months to 17 years) to receive placebo or G-CSF (10 microg per kilogram
      of body weight per day subcutaneously), beginning one day after the completion of
      remission-induction therapy and continuing until the neutrophil count was greater
      than or equal to 1000 per cubic millimeter for two days. The clinical and
      laboratory effects of this therapy were documented for 21 days. The area under
      the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both
      groups. RESULTS: Responses to the growth factor could be assessed in 148 patients
      (73 in the G-CSF group and 75 in the placebo group). G-CSF treatment did not
      significantly lower the rate of hospitalization for febrile neutropenia (58
      percent in the G-CSF group vs. 68 percent in the placebo group; relative risk,
      0.85; 95 percent confidence interval, 0.59 to 1.16), increase the likelihood of
      event-free survival at three years (83 percent in both groups), or decrease the
      number of severe infections (five in the G-CSF group vs. six in the placebo
      group). Patients treated with G-CSF had shorter median hospital stays (6 days vs.
      10 days, P=0.011) and fewer documented infections (12 vs. 27, P=0.009). The
      median total costs of supportive care were similar in the G-CSF and placebo
      groups ($8,768 and $8,616, respectively). Among patients who did not have febrile
      neutropenia during the first week of G-CSF or placebo injections, higher systemic
      exposure to the growth factor on day 7 was significantly related to a lower
      probability of subsequent hospitalization (P=0.049). CONCLUSIONS: G-CSF treatment
      had some clinical benefit in children who received induction chemotherapy for
      acute lymphoblastic leukemia, but it did not reduce the rate of hospitalization
      for febrile neutropenia, prolong survival, or reduce the cost of supportive care.

PMID- 9187069
TI  - Rapid measurement of urinary trypsinogen-2 as a screening test for acute
      pancreatitis.
AB  - BACKGROUND: Acute pancreatitis can be difficult to diagnose. We developed a rapid
      dipstick screening test for pancreatitis, based on the immunochromatographic
      measurement of urinary trypsinogen-2. METHODS: We prospectively compared the
      urinary trypsinogen-2 dipstick test with a quantitative urinary trypsinogen-2
      assay, a urinary dipstick test for amylase, and serum and urinary amylase assays
      in 500 consecutive patients with acute abdominal pain at two emergency
      departments. Acute pancreatitis was diagnosed according to standardized criteria.
      RESULTS: The urinary trypsinogen-2 dipstick test was positive in 50 of the 53
      patients with acute pancreatitis (sensitivity, 94 percent), including all 7 with
      severe pancreatitis. Two patients with urinary trypsinogen-2 concentrations below
      the sensitivity threshold of the test (50 ng per milliliter) and one with a very
      high concentration had false negative results. The test was also positive in 21
      of the 447 patients without pancreatitis (specificity, 95 percent), including 7
      with abdominal cancers, 3 with cholangitis, and 2 with chronic pancreatitis. The
      sensitivity and specificity of the dipstick test were similar to those of the
      quantitative urinary trypsinogen-2 assay and higher than those of the urinary
      amylase dipstick test. The serum amylase assay had a sensitivity of 85 percent
      (with a cutoff value of 300 U per liter for the upper reference limit) and a
      specificity of 91 percent. The sensitivity and specificity of the urinary amylase
      assay (cutoff value, 2000 U per liter) were 83 and 88 percent, respectively.
      CONCLUSIONS: In patients with acute abdominal pain seen in the emergency
      department, a negative dipstick test for urinary trypsinogen-2 rules out acute
      pancreatitis with a high degree of probability. A positive test usually
      identifies patients in need of further evaluation.

PMID- 9187070
TI  - Images in clinical medicine. Annular pancreas.

PMID- 9187071
TI  - Physician-assisted death in psychiatric practice in the Netherlands.
AB  - BACKGROUND: In 1994 the Dutch Supreme Court ruled that in exceptional instances,
      physician-assisted suicide might be justifiable for patients with unbearable
      mental suffering but no physical illness. We studied physician-assisted suicide
      and euthanasia in psychiatric practice in the Netherlands. METHODS: In 1996, we
      sent questionnaires to 673 Dutch psychiatrists - about half of all such
      specialists in the country - and received 552 responses from the 667 who met the
      study criteria (response rate, 83 percent). We estimated the annual frequencies
      of requests for physician-assisted suicide by psychiatrists and actual instances
      of assistance. RESULTS: Of the respondents, 205 (37 percent) had at least once
      received an explicit, persistent request for physician-assisted suicide and 12
      had complied. We estimate there are 320 requests a year in psychiatric practice
      and 2 to 5 assisted suicides. Excluding those who had ever assisted, 345 of the
      respondents (64 percent) thought physician-assisted suicide because of a mental
      disorder could be acceptable, including 241 who said they could conceive of
      instances in which they themselves would be willing to assist. The most frequent
      reasons for refusing were the belief that the patient had a treatable mental
      disorder, opposition to assisted suicide in principle, and doubt that the
      suffering was unbearable or hopeless. Most, but not all, patients who had been
      assisted by their psychiatrists in suicide had both a mental disorder and a
      serious physical illness, often in a terminal phase. Thirty percent of the
      respondents had been consulted at least once by a physician in another specialty
      about a patient's request for assisted death. The annual number of such
      consultations was estimated at 310, about 3 percent of the estimated 9700
      requests for euthanasia or physician-assisted suicide in medical practice.
      CONCLUSIONS: Explicit requests for physician-assisted suicide are not uncommon in
      psychiatric practice in the Netherlands, but these requests are rarely granted.
      Psychiatric consultation for medical patients who request physician-assisted
      death is relatively rare.

PMID- 9187073
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 19-1997. A 57-year-old man with a bloody pericardial effusion.

PMID- 9187072
TI  - Seminars in medicine of the Beth Israel Deaconess Medical Center. Neuroendocrine
      responses to starvation and weight loss.

PMID- 9187074
TI  - Postmenopausal hormone-replacement therapy--time for a reappraisal?

PMID- 9187075
TI  - Hematopoietic growth factors--not whether, but when and where.

PMID- 9187076
TI  - Psychiatry and assisted suicide in the United States.

PMID- 9187077
TI  - Listening in on the Duke University Private Sector Conference.

PMID- 9187078
TI  - Wild-type myoblasts rescue the ability of myogenin-null myoblasts to fuse in
      vivo.
AB  - Skeletal muscle is formed via a complex series of events during embryogenesis.
      These events include commitment of mesodermal precursor cells, cell migration,
      cell-cell recognition, fusion of myoblasts, activation of structural genes, and
      maturation. In mice lacking the bHLH transcription factor myogenin, myoblasts are
      specified and positioned correctly, but few fuse to form multinucleated fibers.
      This indicates that myogenin is critical for the fusion process and subsequent
      differentiation events of myogenesis. To further define the nature of the
      myogenic defects in myogenin-null mice, we investigated whether myogenin-null
      myoblasts are capable of fusing with wild-type myoblasts in vivo using chimeric
      mice containing mixtures of myogenin-null and wild-type cells. Chimeric embryos
      demonstrated that myogenin-null myoblasts readily fused in the presence of wild
      type myoblasts. However, chimeric myofibers did not express wild-type levels of
      muscle-specific gene products, and myofibers with a high percentage of mutant
      nuclei appeared abnormal, suggesting that the wild-type nuclei could not fully
      rescue mutant nuclei in the myofibers. These data demonstrate that myoblast
      fusion can be uncoupled from complete myogenic differentiation and that myogenin
      regulates a specific subset of genes with diverse function. Thus, myogenin
      appears to control not only transcription of muscle structural genes but also the
      extracellular environment in which myoblast fusion takes place. We propose that
      myogenin regulates the expression of one or more extracellular or cell surface
      proteins required to initiate the muscle differentiation program.

PMID- 9187079
TI  - Analysis of neural crest cell migration in Splotch mice using a neural crest
      specific LacZ reporter.
AB  - Studies on the mouse Splotch (Sp) mutation, a deletion in the transcription
      factor Pax-3, have revealed that Pax-3 is essential for normal development of the
      neural crest. We have investigated the defect in neural crest development using a
      Wnt-l::LacZ reporter construct to mark neural crest cells. Staining embryos for
      beta-galactosidase activity at different developmental stages revealed a severe
      reduction in the number of neural crest cells which emigrated from the neural
      tube at the vagal and rostral trunk levels. At the caudal thoracic, lumbar, and
      sacral levels there was a complete loss of neural crest cell emigration. In
      contrast to previous work in culture, we saw no evidence for any delay in the
      onset of neural crest cell migration at anterior levels. Pax-3 is expressed in
      the dorsal neural tube, where the neural crest cells originate, in migrating
      neural crest cells, and in somitic cells along the migratory pathway. Hence, it
      is not clear which aspect of the Pax-3 expression accounts for the observed
      phenotype. We addressed this problem by transplanting neural tissue between mouse
      and chick embryos. Our studies indicate that the defect in the Splotch mutation
      is not intrinsic to the neural crest cells themselves, but appears to reflect
      inappropriate cell interactions either within the neural tube or between the
      neural tube and the somite.

PMID- 9187080
TI  - N-cadherin-catenin interaction: necessary component of cardiac cell
      compartmentalization during early vertebrate heart development.
AB  - During early heart development the expression pattern of N-cadherin, a calcium
      dependent cell adhesion molecule, suggests its involvement in morphoregulation
      and the stabilization of cardiomyocyte differentiation. N-cadherin's adhesive
      activity is dependent upon its interaction with the intracellular catenins. An
      association with alpha-catenin and beta-catenin also is believed to be involved
      in cell signaling. This study details the expression patterns of alpha-catenin,
      beta-catenin, and gamma-catenin, during definition of the cardiac cell population
      as distinct compartments in the anterior regions of the chick embryo between
      stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+
      from a uniform pattern in vivo, to specific cell clusters that demarcate areas
      where mesoderm separation is initiated, suggests that the N-cadherin/catenin
      complex is involved in boundary formation and in the subsequent cell sorting. The
      latter two processes lead to the specification and formation of the somatic and
      cardiac splanchnic mesoderm. N-cadherin colocalized with alpha- and beta-catenin
      at the cell membrane before and during the time that its expression becomes
      restricted to the lateral mesoderm and continues cephalocaudad into stage 8.
      These proteins continue to colocalize in the myocardium of the tubular heart.
      Plakoglobin is not expressed in this region during stages 6-8, but is detected in
      the myocardium later at stage 13. The observed in vivo expression patterns of
      alpha-catenin, beta-catenin, and plakoglobin suggest that these proteins are
      directly linked with the developmental regulation of cell junctions, as cardiac
      cells become stably committed and phenotypically differentiated to eventually
      form a mature myocardium. The localization of N-CAM also was analyzed during
      these stages to determine whether the N-cadherin-catenin localization was unique
      or whether other cell adhesion molecules were expressed similarly. The results
      indicate that the unique pattern of N-cadherin expression is not shared with N
      CAM. We also show that perturbation of N-cadherin using a function perturbing N
      cadherin antibody (NCD-2) inhibits normal early heart development and myogenesis
      in a cephalocaudad, stage-dependent manner. We propose a model whereby myocardial
      cell compartmentalization also defines the endocardial population. The presence
      of beta-catenin suggests that a similar signaling pathway involving Wnt
      (wingless)-mediated events may function in myocardial cell compartmentalization
      during early vertebrate heart development, as in Drosophila contractile vessel
      development.

PMID- 9187081
TI  - Role of the Dlx homeobox genes in proximodistal patterning of the branchial
      arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of
      proximal skeletal and soft tissue structures derived from the first and second
      arches.
AB  - The Dlx homeobox gene family is expressed in a complex pattern within the
      embryonic craniofacial ectoderm and ectomesenchyme. A previous study established
      that Dlx-2 is essential for development of proximal regions of the murine first
      and second branchial arches. Here we describe the craniofacial phenotype of mice
      with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses
      of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that
      the Dlx genes regulate proximodistal patterning of the branchial arches. This
      analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in
      craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique
      abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are
      expressed in the proximal and distal first and second arches, yet only the
      proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, 
      5, and -6 provide evidence for a model that predicts the region-specific
      requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have
      ectopic skull components that resemble bones and cartilages found in
      phylogenetically more primitive vertebrates.

PMID- 9187082
TI  - Distinct signal/response mechanisms regulate pax1 and QmyoD activation in
      sclerotomal and myotomal lineages of quail somites.
AB  - Pax1 and QmyoD are early sclerotome and myotome-specific genes that are activated
      in epithelial somites of quail embryos in response to axial notochord/neural tube
      signals. In situ hybridization experiments reveal that the developmental kinetics
      of activation of pax1 and QmyoD differ greatly, suggesting that myotome and
      sclerotome specification are controlled by distinct developmental mechanisms.
      pax1 activation always occurs in somite IV throughout development, indicating
      that pax1 regulation is tightly coordinated with early steps in somite
      maturation. In contrast, QmyoD is delayed and does not occur until embryos have
      12-14 somites. At this time, QmyoD is the first of the myogenic regulatory factor
      (MRF) genes to be activated in preexisting somites in a rapid, anterior to
      posterior progression until the 22 somite stage, after which time QmyoD is
      activated in somite I immediately following somite formation. Experiments
      involving transplantation of newly formed somites to ectopic sites along the
      anterior to posterior embryonic axis were performed to distinguish the
      contributions of axial signals and somite response pathways to the developmental
      regulation of pax1 and QmyoD. These studies show that pax1 activation is
      regulated by somite formation and maturation, not by the availability of axial
      signals, which are expressed prior to somite formation. In contrast, the delayed
      activation of QmyoD is controlled by developmental regulation of the production
      of axial signals as well as by the competence of somites to respond to these
      signals. These somite transplantation studies, therefore, provide a basis for
      understanding the different developmental kinetics of activation of pax1 and
      QmyoD during sclerotome and myotome specification, and suggest specific molecular
      models for the developmental regulation of myotome and sclerotome formation in
      somites through distinct signal/response pathways.

PMID- 9187083
TI  - In vitro preselection of gene-trapped embryonic stem cell clones for
      characterizing novel developmentally regulated genes in the mouse.
AB  - We have developed an in vitro gene trap screen for novel murine genes that allows
      one to determine, prior to making chimeric or transgenic animals, if these genes
      are expressed in one or more specific embryonic tissues. Totipotent embryonic
      stem (ES) cells are infected with a retroviral gene trap construct encoding a
      selectable lacZ/neo fusion gene, which is expressed only if the gene trap inserts
      within an active transcription unit. G418-resistant ES cell clones are induced to
      differentiate in vitro, and neurons, glia, myocytes, and chondrocytes are
      screened for expression of beta-galactosidase (beta-gal). cDNAs of the gene trap
      transcripts are obtained by 5' rapid amplification of cDNA ends and are sequenced
      to determine if they represent novel genes. In situ hybridization analyses show
      that trapped genes are expressed in vivo within the cell types that express beta
      gal in vitro. Gene traps and their wild-type alleles are characterized in terms
      of copy number, alternate splicing of their transcripts, and the proportion of
      endogenous mRNA sequence that is replaced by lacZ/neo in the hybrid gene trap
      transcript. This approach, which we term "in vitro preselection," is more
      economical than standard in vivo gene trap screening because tissue-specific
      expression of probable knockout alleles is verified before transgenic animals are
      generated. These results also highlight the utility of ES cell differentiation in
      vitro as a method with which to study the molecular mechanisms regulating the
      specification and commitment of a variety of cell and tissue types.

PMID- 9187084
TI  - Division of labor of Schwann cell integrins during migration on peripheral nerve
      extracellular matrix ligands.
AB  - Myelination of the peripheral nervous system (PNS) requires the migration of
      Schwann cells during both development and regeneration. We have characterized the
      expression pattern of Schwann cell integrins and analyzed their role in migration
      on different ECM substrates known to be present within the PNS. We found that
      Schwann cells in cell culture express four beta1 integrins, alpha1 beta1, alpha2
      beta1, alpha6 beta1, and another unidentified beta1 integrin, as well as two
      alpha v integrins, alpha v beta3 and alpha v beta8. Using the Varani migration
      assay, we found that laminin-1, laminin-2 (merosin), and fibronectin increased
      Schwann cell migration, while vitronectin and collagen did not increase migration
      compared to an uncoated plastic substrate. Schwann cell migration on laminin-1
      and laminin-2 (merosin) was blocked by antibodies against beta1 integrins, but
      not affected by RGD peptides or antibodies against beta3 integrins. In contrast,
      migration on fibronectin was unaffected by antibodies against beta1 and beta3
      integrins but was blocked by RGD peptides. This in vitro study shows that there
      is a division of labor of Schwann cell integrins in the regulation of migration
      on peripheral nerve ECM components; beta1 integrins mediate migration on laminin
      1 and laminin-2 (merosin), while alpha v integrins mediate migration on
      fibronectin. Taken together, these results suggest that multiple interactions
      between Schwann cell integrins and ECM within the PNS will contribute to Schwann
      cell migration during myelination of the PNS.

PMID- 9187085
TI  - Regulation of paraxis expression and somite formation by ectoderm- and neural
      tube-derived signals.
AB  - During vertebrate embryogenesis, the paraxial mesoderm becomes segmented into
      somites, which form as paired epithelial spheres with a periodicity that reflects
      the segmental organization of the embryo. As a somite matures, the ventral region
      gives rise to a mesenchymal cell population, the sclerotome, that forms the axial
      skeleton. The dorsal region of the somite remains epithelial and is called
      dermomyotome. The dermomyotome gives rise to the trunk and limb muscle and to the
      dermis of the back. Epaxial and hypaxial muscle precursors can be attributed to
      distinct somitic compartments which are laid down prior to overt somite
      differentiation. Inductive signals from the neural tube, notochord, and overlying
      ectoderm have been shown to be required for patterning of the somites into these
      different compartments. Paraxis is a basic helix-loop-helix transcription factor
      expressed in the unsegmented paraxial mesoderm and throughout epithelial somites
      before becoming restricted to epithelial cells of the dermomyotome. To determine
      whether paraxis might be a target for inductive signals that influence somite
      patterning, we examined the influence of axial structures and surface ectoderm on
      paraxis expression by performing microsurgical operations on chick embryos. These
      studies revealed two distinct phases of paraxis expression, an early phase in the
      paraxial mesoderm that is dependent on signals from the ectoderm and independent
      of the neural tube, and a later phase that is supported by redundant signals from
      the ectoderm and neural tube. Under experimental conditions in which paraxis
      failed to be expressed, cells from the paraxial mesoderm failed to epithelialize
      and somites were not formed. We also performed an RT-PCR analysis of combined
      tissue explants in vitro and confirmed that surface ectoderm is sufficient to
      induce paraxis expression in segmental plate mesoderm. These results demonstrate
      that somite formation requires signals from adjacent cell types and that the
      paraxis gene is a target for the signal transduction pathways that regulate
      somitogenesis.

PMID- 9187086
TI  - Genetic relationships between the mutations spade and Sternopleural and the
      wingless gene in Drosophila development.
AB  - In Drosophila melanogaster, there are cases in which gene products contributing
      to the same developmental event may derive from closely adjacent transcription
      units and may even share cis-regulatory sequences. Correct recognition of such
      genomic organization is central to an understanding of developmental mechanisms.
      The adult phenotypes of combinations between the mutations spade, Sternopleural,
      and wingless suggest that they are lesions in functionally related genes within
      the same chromosomal region. wingless mutations fail to complement the recessive
      mutation spade. The spade mutation, as previously shown, behaves as a lesion in a
      regulatory site of wingless, sited 5' to the transcription unit, and is concerned
      with particular postembryonic functions of wingless. While showing wingless-like
      phenotypes in combination with Sternopleural, even lethal alleles of wingless
      complement the recessive lethality of Sternopleural alleles. Mutations in
      Sternopleural increase the severity of wingless phenotypes in many wingless
      dependent processes during postembryonic development, and this interaction can
      occur when the only functional copies of Sp or wg are located in either opposing
      chromosomes or the same chromosome. This is inconsistent with previous attempts
      to define Sp as a regulatory allele of wg and explain the phenotypes that result
      from combinations of Sp and wg by means of transvection. We have analyzed a new
      EMS-induced allele of Sternopleural that is more severe than the original allele,
      which also argues for Sp being a separate, mutable genetic locus rather than a
      regulatory allele of wg. Finally, we have a revertant of Sternopleural (Sp[Rv1])
      that behaves as a genetic null allele of wg, but causes ventral-to-dorsal
      transformations in combination with wg(P), which is not observed in combinations
      of wg null alleles with wg(P). Because wg(P) is the result of an inversion and
      because inversions inhibit transvection, the increased severity observed in
      Sp(Rv1)/wg(P) in comparison to wg(null)/Sp(Rv1) animals cannot be explained by an
      absence of transvection. Therefore, the two Sternopleural mutations most
      reasonably define an independent gene located 3' to the wingless gene and having
      strong functional synergism with it.

PMID- 9187087
TI  - Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E
      cadherin.
AB  - Trophectoderm epithelium formation, the first visible differentiation process
      during mouse embryonic development, is affected in embryos lacking the cell
      adhesion molecule E-cadherin. Here we analyze the developmental potential of such
      E-cadherin-negative embryos, focusing on the organization of cell junctions and
      the cytoskeleton. To do this we used antibodies directed against alpha-, beta-,
      or gamma-(plakoglobin)-catenin and junctional and cytoskeletal proteins including
      ZO-1 and occludin (tight junctions), desmoglein1 (desmosomes), connexin43 (gap
      junctions), and EndoA (cytokeratin intermediate filaments). Membrane localization
      of alpha- and beta-catenin, and ZO-1, as well as cortical actin filament
      organization were abnormal in E-cadherin-negative embryos, and the expression
      levels of alpha- and beta-catenin were dramatically reduced, all suggesting a
      regulatory role for E-cadherin in forming the cadherin-catenin complex. In
      contrast, the membrane localization of plakoglobin, occludin, desmoglein1,
      connexin43, and cytokeratin filaments appeared unaltered. The unusual
      morphogenesis in E-cadherin-negative embryos apparently reflects defects in the
      molecular architecture of a supermolecular assembly involving zonulae adherens,
      tight junctions, and cortical actin filament organization, although the
      individual structures still appeared normal in electron microscopical analysis.

PMID- 9187088
TI  - A molecular phylogeny of the Aphidiinae (Hymenoptera: Braconidae).
AB  - Phylogenetic relationships within the Aphidiinae, and between this and other
      subfamilies of Braconidae (Hymenoptera), were investigated using sequence data
      from three genes: elongation factor-1alpha, cytochrome b, and the second
      expansion segment of the 28S ribosomal subunit. Variation in both protein-coding
      genes was characterized by a high level of homoplasy, but analysis of the
      expansion segment--robust over a range of alignment methods and parameters
      resolved some of the older divergences. Parsimony analysis of the combined data
      suggests the following tribal relationships: (Ephedrini + (Praini + (Aphidiini +
      Trioxini))). In addition, the cyclostome subfamilies were found to form a clade
      separate from the Aphidiinae, but relationships between the Aphidiinae and the
      noncyclostome braconids could not be resolved. The inferred phylogeny also
      supported a secondary loss of internal pupation within the Praini and a
      polyphyletic origin of endoparasitism within the Braconidae.

PMID- 9187089
TI  - Phylogenetic relationships of cottontails (Sylvilagus, Lagomorpha): congruence of
      12S rDNA and cytogenetic data.
AB  - The genus Sylvilagus, which comprises the New World cottontail rabbits, contains
      several commercially important as well as endangered (or threatened) species.
      Understanding the evolution of this group is pertinent to their management and
      conservation. The purpose of this study was to examine the evolutionary history
      of the cottontails using sequence data from the mitochondrial 12S rRNA gene. The
      12S data provide a robust phylogeny which was supported under a variety of
      phylogenetic approaches and transition/transversion (Ti/Tv) weighting schemes.
      Stem and loop regions of the gene were analyzed separately and two different
      methods of estimating Ti/Tv ratios were employed. The phylogeny obtained was
      consistent with available cytogenetic information. The 12S data indicate that
      separate generic status for the pygmy rabbit, Brachylagus idahoensis, is
      warranted based on its phylogenetic position and sequence divergence values.
      Additionally, the taxa which are geographically adjacent are also
      phylogenetically closely related; for example, the marsh rabbit, S. palustris,
      and the swamp rabbit, S. aquaticus, are sister taxa, as are the mountain
      cottontail, S. nuttallii, and desert cottontail, S. audubonii. This finding
      suggests that recent vicariance events might explain the diversification of
      several cottontail lineages.

PMID- 9187090
TI  - A cladistic analysis of mitochondrial ribosomal DNA from the Bovidae.
AB  - There is a huge data base of genetic information for the domestic artiodactyl
      species Bos taurus (cow), Ovis aries (sheep), and Capra hircus (goat). However,
      the phylogenetic relationships of these economically critical taxa and their
      close relatives, family Bovidae, remain for the most part unresolved. In this
      report, we aligned new mitochondrial (mt) 12S and 16S ribosomal (r) DNA sequences
      from 26 bovid taxa with published sequences. Phylogenetic analyses of the more
      than 64 kilobases of mt rDNA from 57 taxa support a basal division in the Bovidae
      that separates Bos and its close relatives from Capra, Ovis, and their kin. As
      suggested by previous molecular and morphological studies, "antelopes" are a
      paraphyletic assemblage. Caprinae (sheep, goats, goat antelopes, and musk oxen)
      groups consistently with hippotragine and alcelaphine antelopes, while Bovini
      (cattle and buffaloes) clusters with tragelaphine and boselaphine antelopes. The
      traditional tribal subdivisions of Bovidae are supported in most cases, but there
      are exceptions within Caprinae and Antilopinae (gazelles and close relatives).
      The rDNA data consistently place the enigmatic genera Pelea, Pantholops, and
      Saiga, but the origin of Aepyceros, the impala, remains obscure. Combined
      phylogenetic analyses of the rDNA data with the skeletal characters of Gentry
      (1992) were used to assess the stability of the molecular results.

PMID- 9187091
TI  - Consistency, characters, and the likelihood of correct phylogenetic inference.
AB  - Computer simulations of character-state evolution in 8, 16, 32, and 64 ingroup
      taxa with a known set of relationships demonstrate that the maximum probability
      of correct phylogenetic inference increases with the number of variable (or
      informative) characters and their consistency index and decreases with the number
      of taxa, when the consistency index has been standardized to eliminate its
      dependence on the number of taxa. Equations for the probability of correct
      phylogenetic inference and for the standardized consistency indices (including or
      excluding autapomorphies) are derived. Given that actual studies based on DNA
      restriction sites and sequences generate more characters with a higher level of
      consistency than comparable studies based on morphology, calculations suggest
      that such molecular studies may often provide a more precise guide to
      phylogenetic relationships.

PMID- 9187093
TI  - Robustness of the estimator of the index of dispersion for DNA sequences.
AB  - If substitutions in DNA sequences follow a Poisson process, the ratio of the
      variance in the number of substitutions to the mean number of substitutions (the
      index of dispersion) should equal 1. In this paper, the robustness of the
      commonly applied estimator of the index of dispersion in replacement sites and
      silent sites to various assumptions regarding DNA evolution is explored using
      simulation methods. The estimate of the index of dispersion may be strongly
      biased if the assumptions of the model of substitution are violated. However, the
      results of this study support the conclusions of studies by Gillespie and Ohta
      that the process of substitution in replacement sites is overdispersed. This
      result contradicts those of a recent study and shows that the high index of
      dispersion for replacement sites is not an artifact caused by the method of
      estimation.

PMID- 9187092
TI  - A survey of homeobox genes in Chaetopterus variopedatus and analysis of
      polychaete homeodomains.
AB  - A survey of genomic DNA from the polychaete Chaetopterus variopedatus was
      conducted using the polymerase chain reaction. Twelve unique homeobox-containing
      gene fragments were recovered. Phylogenetic analysis indicates that seven of the
      fragments are from genes belonging to Hox homeobox classes. Other fragments show
      orthology with Xlox, caudal, and Prh homeobox classes, with two fragments not
      definitely assignable to a homeobox class by our analysis. Orthology with gene
      sequences reported for the polychaete Ctenodrilus serratus, by Dick and Buss
      (1994), was calculated and indicated that at least eight of the C. variopedatus
      fragments are homologous to these previously reported sequences. Tabulation of
      the Hox gene relationships suggest that polychaetes have representative genes of
      each of the Hox cognate groups except Abd-B. This conclusion further suggests
      that the Hox cluster in the basal protostome ancestor had already undergone the
      gene duplications leading to the complete complement of homeotic genes known in
      Drosophila, with the possible loss of Abd-B in the polychaete lineage.

PMID- 9187094
TI  - Correlation of functional domains and rates of nucleotide substitution in
      cytochrome b.
AB  - Distinguishing noise from signal presents a problem when DNA sequences are used
      for phylogeny reconstruction. Multiple substitutions at sites are a primary cause
      of noise and this is compounded by variation in substitution rates among sites.
      For protein-coding genes, one method used to determine if data are noisy is to
      assess levels of saturation of substitutions by codon position. However, this
      procedure may not be a fine enough filter for assessing noise. Variation in
      substitution rates may also be caused by constraints on change imposed by the
      function of the protein product. Using a structural model of the cytochrome b
      protein as a template, I divided cyt b sequence data for species within the avian
      family Falconidae (falcons and caracaras) into three functional domains.
      Saturation of substitutions of sequences within these regions was assessed
      graphically. This qualitative determination of saturation was then used to
      differentially weight phylogenetic analysis, resulting in an hypothesis congruent
      with existing cladistic analyses and traditional morphology. These results
      demonstrate that saturation of substitutions is correlated with functional
      regions of cytochrome b and that using this information improves phylogenetic
      inference.

PMID- 9187095
TI  - Molecular systematics of Middle American cichlid fishes and the evolution of
      trophic-types in 'Cichlasoma (Amphilophus)' and 'C. (Thorichthys)'.
AB  - The majority of Middle American cichlids are placed in the informal assemblage
      'Cichlasoma.' The group is divided into eight sections which appear to be based
      primarily on trophic morphology. Although several members of 'Cichlasoma' have
      been used in ecomorphological, behavioral, and biogeographic studies, no
      phylogenetic hypotheses for the group exist. In an attempt to develop a better
      understanding of the phylogenetic relationships of 'cichlasomine' cichlids, we
      examined the evolution of the trophic specialization, substratum-sifting, in two
      sections, 'Cichlasoma (Thorichthys)' and 'C. (Amphilophus),' to determine whether
      the trait reflects common ancestry. We sequenced the complete mitochondrial
      cytochrome b gene for 19 cichlids representing six sections of 'Cichlasoma,' and
      representatives of other Neotropical Cichlidae. Additional cichlid, and
      noncichlid outgroup sequences were included for a total of 22 taxa. The molecular
      phylogeny supports the recognition of the section 'C. (Thoricthys)' as a natural
      group, and we place those cichlids in the genus Thorichthys. The phylogeny also
      depicts 'C. (Amphilophus)' as paraphyletic, with substratum-sifters and
      generalized predators forming separate nonsister clades. We recommend that the
      substratum-sifting clade of the section 'C. (Amphilophus)' be placed in the
      resurrected genus Astatheros. The generalized predator clade of 'C.
      (Amphilophus)' contains only two species, 'C. (A.) citrinellum' and 'C. (A.)
      labiatum,' which we place in the genus Amphilophus. The phylogenetic hypotheses
      generated indicate that the substratum-sifting genera Thorichthys and Amphilophus
      do not share a common ancestor. Reconstruction of the evolution of substratum
      sifting is equivocal, requiring either the independent evolution of the trait on
      two separate occasions or its presence in a more inclusive clade and subsequent
      loss in nonsubstratum sifting species.

PMID- 9187096
TI  - Phylogenetic relationships of the liverworts (Hepaticae), a basal embryophyte
      lineage, inferred from nucleotide sequence data of the chloroplast gene rbcL.
AB  - Sequence data from the chloroplast-encoded gene rbcL were obtained for 24
      liverworts, a basal group of embryophytes. Maximum likelihood and parsimony
      analyses of these data, along with data from other major green plant lineages,
      confirm hypotheses based on morphological data, such as the paraphyly of
      bryophytes, and the basal position of liverworts. Molecular data corroborate the
      deep separation between the complex thalloid and leafy/simple thalloid liverworts
      implied by morphological data, but the monophyly of liverworts could not be
      rejected. The effects of accounting for site-to-site rate heterogeneity in these
      data were examined using maximum likelihood methods. Comparison of trees obtained
      with and without rate heterogeneity showed that simply allowing for heterogeneity
      had a greater improvement on likelihood score than optimization of
      transition/transversion bias. Incorporation of site-to-site rate heterogeneity in
      the larger analysis, however, did not necessarily change which topology was
      favored. Properties of rbcL sequences from the two liverwort groups were
      compared. Significantly different substitution rates were found between
      leafy/simple thalloid and complex thalloid liverwort taxa, with rates of rbcL
      sequence evolution in leafy/simple thalloid taxa being higher and more indicative
      of those of vascular plants, and with those of complex thalloid taxa (such as
      Marchantia) being slower. Codon usage in rbcL in complex thalloid liverworts was
      biased toward NNU and NNA, compared to the leafy/simple thalloid liverworts.
      Although base composition and relative substitution rates differed between the
      two groups, no significant differences were detected within each of the two
      groups of liverworts. The signal present in first and second codon sites versus
      third codon sites was compared. While the third codon positions in rbcL across
      this taxon sampling are highly variable (with only 15 constant sites of 439), the
      trees obtained were in general agreement with trees from the entire data set and
      with trees obtained from independent sources of data. The presence of signal in
      third codon positions across greater than 400 MY of plant evolution means that
      definitions of saturation based on pair-wise comparisons of sequences
      inadequately assess phylogenetic signal.

PMID- 9187097
TI  - Molecules, morphology, and phylogeny: a response to Hedges and Maxson.

PMID- 9187098
TI  - Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light
      in human skin maintained in severe combined immunodeficient mice.
AB  - To study the mechanism and risk of human skin cancer from solar light, we exposed
      human skin transplanted to severe combined immunodeficient mice to daily doses of
      UVB for periods of approximately 2 years. We have succeeded for the first time in
      inducing cancer and solar (actinic) keratosis in human skin by UVB. Of 18 normal
      skins exposed to doses of 7.3 x 10(5) to 1.8 x 10(6) J/m2, 14 actinic keratoses
      (77.8%) and 3 squamous cell carcinomas (16.7%) developed, whereas neither actinic
      keratosis nor cancer was observed in 15 human skins not exposed to UVB. Each
      human skin showed a different susceptibility, and skins sensitive for actinic
      keratosis were also sensitive for cancer induction. Among p53 mutations at
      various sites, mutation at codon 242 (C TGC --> C CGC; Cys --> Arg) was
      specifically observed in both skin cancers and actinic keratoses. Furthermore,
      double or triple mutations were induced in all UVB-induced skin cancers and in
      three of eight actinic keratoses. Most of the mutations (17 of 20) occurred at
      dipyrimidine sites.

PMID- 9187099
TI  - Medulloblastomas of the desmoplastic variant carry mutations of the human
      homologue of Drosophila patched.
AB  - Inactivating mutations in the PTCH gene, a human homologue of the Drosophila
      segment polarity gene patched, have been identified recently in patients with
      nevoid basal cell carcinoma syndrome. These patients are predisposed to various
      neoplasias including basal cell carcinomas and medulloblastomas (MBs). To
      determine the involvement of PTCH in sporadic MBs, which represent the most
      frequent malignant brain tumors in children, we screened for PTCH alterations in
      an unselected panel of 64 biopsy samples from 62 patients and four continuous MB
      cell lines, all derived from patients with sporadic MBs. Using single-strand
      conformational polymorphism analysis, we screened exons 2-22 and detected
      nonconservative PTCH mutations in 3 of 11 samples from sporadic cases of the
      desmoplastic variant of MB but none in 57 MBs with classical (nondesmoplastic)
      histology. In two of the tumors with mutations and in two additional desmoplastic
      cases, loss of heterozygosity was found at 9q22. These findings suggest that PTCH
      represents a tumor suppressor gene involved in the development of the
      desmoplastic variant of MB.

PMID- 9187100
TI  - Constitutive expression of mature transforming growth factor beta1 in the liver
      accelerates hepatocarcinogenesis in transgenic mice.
AB  - Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte
      growth both in vivo and in vitro. In this study, we analyzed the effects of TGF
      beta1 on both naturally occurring and diethylnitrosamine-induced
      hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c
      myc/TGF-beta1 mice in which the expression of both transgenes was targeted to the
      liver. Hepatocellular tumors developed spontaneously in 59% (10 of 17) of the TGF
      beta1 mice by 16-18 months of age. Coexpression of TGF-beta1 and c-myc transgenes
      in the liver accelerated hepatic tumor growth in both the presence and absence of
      carcinogenic treatment. Moreover, diethylnitrosamine-initiated tumors in the c
      myc/TGF-beta1 mice showed a high rate of malignant conversion associated with a
      reduced expression or lack of TGF-beta receptor type II. The results suggest that
      overexpression of TGF-beta1 may contribute to liver carcinogenesis and that loss
      of TGF-beta receptor type II transduced inhibitory growth signals and up
      regulation of c-myc are critical steps in liver tumor progression.

PMID- 9187101
TI  - Ionizing radiation mediates expression of cell adhesion molecules in distinct
      histological patterns within the lung.
AB  - Inflammatory cell infiltration of the lung is a predominant histopathological
      change that occurs during radiation pneumonitis. Emigration of inflammatory cells
      from the circulation requires the interaction between cell adhesion molecules on
      the vascular endothelium and molecules on the surface of leukocytes. We studied
      the immunohistochemical pattern of expression of cell adhesion molecules in lungs
      from mice treated with thoracic irradiation. After X-irradiation, the endothelial
      leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the
      pulmonary endothelium of larger vessels and minimally in the microvascular
      endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was
      expressed in the pulmonary capillary endothelium and minimally in the endothelium
      of larger vessels. Radiation-mediated E-selectin expression was first observed at
      6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation.
      ICAM-1 and E-selectin expression persisted for several days. P-selectin is
      constitutively expressed in Weibel-Palade bodies in the endothelium, which moved
      to the vascular lumen within 30 min after irradiation. P-selectin was not
      detected in the pulmonary endothelium at 6 h after irradiation. The radiation
      dose required for increased cell adhesion molecule expression within the
      pulmonary vascular endothelium was 2 Gy, and expression increased in a dose
      dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is
      increased in the pulmonary endothelium following thoracic irradiation. The
      pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one
      another.

PMID- 9187102
TI  - Cytological detection of telomerase activity using an in situ telomeric repeat
      amplification protocol assay.
AB  - A previously reported highly sensitive assay for measuring telomerase activity on
      cell and tissue extracts indicates that most human tumor tissues, but not cells
      adjacent to tumors, have detectable telomerase activity. Although this assay has
      provided a significant amount of information about the presence or absence of
      telomerase activity, it does not indicate whether all cells within a tumor have
      telomerase activity or whether only a subset does. The present report
      demonstrates the ability to advance this technology to an in situ assay. Using
      fluorescent telomerase primers and in situ PCR, we show that telomerase activity
      can be detected at the cellular level. This study demonstrates that telomerase
      activity is not detected in normal cells but is detected in tumor cells of
      clinical specimens and in tumor-derived cell lines.

PMID- 9187103
TI  - Ornithine decarboxylase overexpression leads to increased epithelial tumor
      invasiveness.
AB  - Ornithine decarboxylase (ODC) overexpression cooperates with genetic lesions such
      as an activated c-rasHa to enhance epithelial tumorigenesis. To assess the
      invasiveness of ODC-overexpressing cells, two noninvasive epidermal cell lines,
      nontumorigenic BK-1 cells, and the papilloma-derived cell line SP-1 were infected
      with a replication-defective retrovirus that overexpresses ODC, inoculated into
      deepithelialized rat tracheas, and transplanted into athymic nude mice. After 5
      weeks, ODC-overexpressing BK-1 cells remained localized on the luminal surface of
      the tracheal xenotransplants, whereas the ODC-overexpressing SP-1 cells were
      extremely invasive, with the whole tracheal wall penetrated. This invasiveness of
      ODC-overexpressing SP-1 cells was accompanied by elevated proteinase expression,
      including increased urokinase plasminogen activator activity in ODC
      overexpressing cells and elevated stromelysin-1 mRNA expression in the stromal
      cells of invaded tracheal transplants.

PMID- 9187105
TI  - FHIT gene expression in human ovarian, endometrial, and cervical cancer cell
      lines.
AB  - The fragile histidine triad (FHIT) gene, located at 3p14.2, has been shown to be
      altered in numerous epithelial cancers. Because previous studies have shown a
      loss of heterozygosity and cytogenetic abnormalities at the 3p region in ovarian,
      endometrial, and cervical carcinomas, we examined the status of the FHIT gene in
      14 ovarian, 8 cervical, and 4 endometrial human cancer cell lines. RNA was
      isolated and subjected to reverse transcription-PCR to amplify the FHIT gene
      transcript. Sixty-three % (5 of 8) of cervical cell lines, 14% (2 of 14) of
      ovarian cell lines, and none (0 of 4) of the endometrial cell lines displayed
      aberrantly migrating FHIT transcripts. DNA sequencing demonstrated that the
      aberrantly migrating bands primarily lacked exons 5, 6, and 7 (with other exon
      losses also observed), resulting in shorter mRNA transcripts. Southern blot
      analysis of DNA from five of the cervical carcinomas demonstrated alterations in
      four of them, three of which had exhibited no normally sized FHIT transcripts.
      The results suggest that the expression of the FHIT gene may be altered in
      cervical tumor tissue, potentially implicating this gene in cervical
      tumorigenesis, whereas the involvement of this gene appears to be less important
      in the development of ovarian and endometrial cancer.

PMID- 9187104
TI  - Inhibition of breast cancer tissue aromatase activity and estrogen concentrations
      by the third-generation aromatase inhibitor vorozole.
AB  - In about one-third of advanced breast cancers, estrogen deprivation causes tumor
      regression. Estrogen concentrations in tumor tissue seem to depend largely on
      local production. The aromatase enzyme complex is thought to be the key enzyme in
      this respect. In the present study, the effect of the new third-generation
      nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase
      activity and estrogen concentrations was evaluated. During 7 days preceding
      mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of
      vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase
      activity and estrone and estradiol levels were measured and compared to the
      values of nine untreated postmenopausal breast cancer patients. In treated
      patients, median tissue aromatase activity was 89% lower than that in controls (P
      < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64
      and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05,
      respectively). These results support the hypothesis that depleting the tumor of
      estrogens, thus impairing estrogenic stimulation, is an important mechanism in
      the antitumor activity of aromatase inhibitors.

PMID- 9187106
TI  - Comparative genomic hybridization analysis detects frequent, often high-level,
      overrepresentation of DNA sequences at 3q, 5p, 7p, and 8q in human non-small cell
      lung carcinomas.
AB  - Comparative genomic hybridization analysis was used to identify chromosomal
      imbalances in 20 non-small cell lung carcinoma (NSCLC) biopsies and cell lines.
      The chromosome arms most often overrepresented were 3q (85%), 5p (70%), 7p (65%),
      and 8q (65%), which were observed at high copy numbers in many cases. Other
      common overrepresented sites were 1q, 2p, and 20p. DNA sequence amplification was
      often observed, with the most frequent site being 3q26 (six cases). Other
      recurrent sites of amplification included 8q24, 3q13, 3q28-qter, 7q11.2, 8p11-12,
      12p12, and 19q13.1-13.2. The most frequent underrepresented segment was 3p21
      (50%); other recurrent sites of autosomal loss included 8p21-pter, 15q11.2-13,
      5q11.2-15, 9p, 13q12-14, 17p, and 18q21-qter. These regions of copy number
      decreases are also common sites of allelic loss, further implicating these sites
      as locations of tumor suppressor genes. Although some of the overrepresented
      segments harbor known or suspected oncogenes/growth-regulatory genes, we have
      identified 3q and 5p as new sites that are very frequently overrepresented in
      NSCLC. These findings could represent entry points for the identification of
      novel amplified DNA sequences that may contribute to the development or
      progression of NSCLC.

PMID- 9187107
TI  - Association between cigarette smoking and FHIT gene alterations in lung cancer.
AB  - Epidemiologic data have strongly indicated that cigarette smoking is linked to
      the development of lung cancer. However, little is known of the molecular targets
      of carcinogens contained in tobacco smoke. To identify genetic lesions
      characteristic of tobacco damage, we undertook a molecular analysis of
      microsatellite alterations within the FHIT gene and FRA3B, as well as at an
      independent locus on chromosome 10, D10S197, in lung tumors from heavy smokers
      and in tumors from never smokers. Loss of heterozygosity affecting at least one
      locus of the FHIT gene was observed in 41 of 51 tumors in the smokers group (80%)
      but in only 9 of 40 tumors in nonsmokers (22%). The comparison between the
      frequency of losses in FHIT in smokers and nonsmokers was statistically
      significant (P = 0.0001), whereas no difference in loss of heterozygosity rate
      was observed at D10S197 locus. These findings suggest that FHIT is a candidate
      molecular target of carcinogens contained in tobacco smoke.

PMID- 9187108
TI  - TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine
      phosphatase regulated by transforming growth factor beta.
AB  - It has long been postulated that protein tyrosine phosphatases may act as tumor
      suppressors because of their ability to counteract the oncogenic actions of
      protein tyrosine kinases. Here we report the cloning and characterization of a
      novel human protein tyrosine phosphatase, TEP1. TEP1 contains the protein
      tyrosine phosphatase signature motif, and we show that it possesses an intrinsic
      protein tyrosine phosphatase activity. TEP1 also shares extensive homology with
      tensin, a cytoskeletal protein localized to focal adhesions, and with auxilin, a
      protein involved in synaptic vesicle transport. Immunofluorescence studies show
      that TEP1 is a cytoplasmic protein. The abundance of TEP1 transcription is
      altered in many transformed cells. In the transforming growth factor beta
      sensitive cells, TEP1 expression is rapidly down-regulated by transforming growth
      factor beta, a cytokine shown to be involved in regulating cell adhesion and cell
      motility. We have also mapped the gene encoding TEP1 to chromosome 10q23, a locus
      that is frequently deleted in a variety of human cancers. TEP1 protein is
      identical to the protein encoded by the candidate tumor suppressor gene
      PTEN/MMAC1. Our functional studies of the TEP1 protein suggest that its tumor
      suppressor function may associate with its intrinsic protein tyrosine phosphatase
      activity and its cytoplasmic localization.

PMID- 9187109
TI  - A role for perlecan in the suppression of growth and invasion in fibrosarcoma
      cells.
AB  - Perlecan is a major heparan sulfate proteoglycan of basement membranes and cell
      surfaces. Because of its strategic location and ability to store and protect
      growth factors, perlecan has been implicated in the control of tumor cell growth
      and metastatic behavior. To test the role of perlecan in malignancy, we generated
      several stably transfected clones of HT-1080, a human fibrosarcoma cell line,
      harboring a perlecan cDNA in the antisense orientation. Surprisingly, clones with
      a reduced synthesis of perlecan mRNA and protein core grew faster, formed larger
      colonies in semisolid agar, and induced faster formation of s.c. tumors in nude
      mice than the wild-type cells. Their growth properties in vitro were independent
      of exogenous basic fibroblast growth factor. Reduction of perlecan expression was
      associated with three distinct properties typical of tumor cells with a more
      aggressive phenotype: enhanced migration through 8-microm-pore filter, increased
      invasion in Matrigel-coated filters, and heightened adhesiveness to type IV
      collagen substrata. These results thus provide the first evidence that perlecan
      may inhibit the growth and invasiveness of fibrosarcoma cells in a basic
      fibroblast growth factor-independent pathway and raise the possibility that
      perlecan may prevent the infiltration of host tissues in mesenchymal neoplasms.

PMID- 9187111
TI  - p16 and K-ras gene mutations in the intraductal precursors of human pancreatic
      adenocarcinoma.
AB  - Pancreatic adenocarcinoma is thought to arise from a noninvasive neoplastic
      precursor, the pancreatic intraductal lesion (PIL). Mutations of the K-ras gene
      are known to occur in PILs, but their high prevalence among PILs within the
      general population probably limit the use of K-ras as a marker of eventual
      clinical risk. In search of genetic constellations that might indicate the
      progression of some PILs toward an invasive phenotype, mutations at both the K
      ras and p16 genes were sought within PILs of 10 pancreata resected for
      adenocarcinoma. K-ras mutations were present in most PILs and in nearly all PILs
      having nuclear atypia. In half of the patients, two or more unique K-ras
      mutations were identified among distinct PILs, which is evidence for the separate
      clonal evolution of multiple pancreatic neoplasms within individual patients. p16
      alterations (one homozygous deletion and three point mutations) were found in 4
      of the 10 carcinomas; these four pancreata harbored p16 alterations in three of
      nine PILs, of which one was a "histologically early" lesion. Two patients had p16
      alterations in PILs matching those of the associated carcinomas. p16 mutations
      were not found in PILs of pancreata having wild-type p16 in the carcinoma, nor
      were they found in ducts having normal histology. It is suggested that
      alterations of the p16 gene affect a subset of PILs that contain mutations of the
      K-ras gene and that these mutations might identify high-risk precursors of the
      invasive malignancy.

PMID- 9187110
TI  - Essential role for nuclear phospholipase C beta1 in insulin-like growth factor I
      induced mitogenesis.
AB  - The nucleus has been shown to be a site for the inositol lipid cycle that can be
      affected by treatment of quiescent cells with growth factors such as insulin-like
      growth factor I (IGF-I). Indeed, the exposure of Swiss 3T3 cells to IGF-I results
      in a rapid and transient increase in nuclear phospholipase C (PLC) beta1
      activity. In addition, several other reports have shown the involvement of PLC
      beta1 in nuclear signaling in different cell types. Although the demonstration of
      phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate
      hydrolysis by nuclear PLC beta1 established the existence of nuclear PLC
      signaling, the significance of this autonomous pathway in the nucleus has yet to
      be thoroughly clarified. By inducing both the inhibition of PLC beta1 expression
      by antisense RNA and its overexpression, we show that this nuclear PLC is
      essential for the onset of DNA synthesis following IGF-I stimulation of quiescent
      Swiss 3T3 cells.

PMID- 9187112
TI  - Telomerase activity: a marker to distinguish follicular thyroid adenoma from
      carcinoma.
AB  - The inability to distinguish microinvasive follicular thyroid cancer from benign
      follicular tumors preoperatively presents an important surgical dilemma. We
      examined 44 follicular tumors and found telomerase activity in all 11 follicular
      carcinomas and in 8 of 33 benign follicular tumors. It was undetectable in 22
      normal thyroid tissues adjacent to the tumors. Telomerase activity may thus
      provide a diagnostic marker distinguishing benign from malignant follicular
      thyroid tumors. The ability to identify invasive follicular thyroid tumors could
      avert over 14,000 thyroidectomies annually in the United States, thereby
      significantly decreasing morbidity and health care costs.

PMID- 9187113
TI  - Increased genetic stability of HeLa cells after connexin 43 gene transfection.
AB  - To test the hypothesis that intact gap-junctional intercellular communication
      (GJIC) is necessary for genomic stability, we compared the spontaneous and
      chemically induced mutation frequencies in GJIC-proficient and -deficient HeLa
      cells. Thus, we determined microsatellite instability and mutation frequency in
      the HPRT gene in parental HeLa cells, which have no GJIC ability, and in HeLa
      cells in which GJIC was restored by transfection with the connexin 43 (Cx43)
      gene. When HeLa cells with (Cx43+) or without Cx43 gene (Cx43-) were treated with
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or methylnitrosourea, the Cx43+ cells
      survived better than Cx43- cells. The mutation frequency at CA repeats was
      measured with a shuttle vector; in the vector, the coding region of the beta
      galactosidase gene was rendered out of frame by insertion of CA repeats, and the
      frame could be restored by insertion or deletion mutations of the CA repeats. The
      mutation frequency at CA repeats was 2-fold lower in Cx43+ cells than in Cx43-,
      both before and after exposure to MNNG or methylnitrosourea (P < 0.05). The
      frequency of spontaneous HPRT gene mutations, selected by their resistance to 6
      thioguanine, was 3-fold lower in Cx43+ cells than Cx43- cells. Similarly, the
      frequency of MNNG-induced HPRT mutations was significantly higher in Cx43- cells
      (P < 0.001). Similar results were obtained even when the mutant selection process
      was carried out in the presence of alpha-glycyrrhetinic acid, a long-term
      inhibitor of GJIC, suggesting that the observed effect is not due to unwanted
      killing of cells by GJIC-mediated metabolic cooperation. Thus, our data
      demonstrate that HeLa cells transfected with the Cx43 gene become more resistant
      to spontaneous as well as chemically induced genetic changes.

PMID- 9187114
TI  - Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA
      glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue.
AB  - 8-Hydroxyguanine (8-OH-G) is one of the major DNA oxidation products implicated
      in mutagenesis induced by oxygen radical-forming agents, including ionizing
      radiation. It is also believed to be involved in spontaneous mutation induced by
      metabolically produced oxygen radicals. A mammalian homologue of 8-OH-G
      glycosylase/apurinic, apyrimidinic lyase (mutM homologue, MMH) has been
      identified in the EST database (for expressed sequence tags) through a homology
      search with yeast OGG1 protein. The human MMH protein (hMMH), 34% identical to
      the yeast OGG1 protein, is a member of the DNA repair protein superfamily. The
      hMMH gene was composed of seven exons, with the alternate last exon, exon 8,
      producing three major alternative splicing isoforms, because splicing of the
      sixth intron was optional. The hMMH protein expressed in Escherichia coli
      revealed the glycosylase activity and apurinic, apyrimidinic lyase activity on
      duplex DNA containing 8-OH-G. The hMMH protein can rescue a spontaneous mutator
      strain of E. coli lacking mutM and mutY. By the introduction of recombinant hMMH,
      the rate of mutation, the formation of rifampicin-resistant revertants, was
      reduced by 4-7 fold. Genomic structure analysis showed that 3' exons of the hMMH
      gene are transcribed on the antisense strand of the calcium-dependent calmodulin
      kinase 1 gene.

PMID- 9187115
TI  - Factors affecting topotecan-induced programmed cell death: adhesion protects
      cells from apoptosis and impairs cleavage of poly(ADP-ribose)polymerase.
AB  - We have evaluated the influence of anchorage status together with endogenous
      levels of bcl-2 family members on the ability of the topoisomerase I inhibitor,
      topotecan (TPT), to induce programmed cell death (PCD) in human colon, breast,
      lymphoid, and cervical cancer cell lines. As part of this study, we assessed the
      use of measuring poly(ADP-ribose) polymerase (PARP) cleavage by Western blot, as
      an index of apoptosis, relative to measuring chromatin condensation by acridine
      orange analysis. Our results show a strong correlation between both assays,
      indicating that PARP cleavage is an accurate method to examine PCD. We have
      encountered a strong association between cell attachment and sensitivity to TPT
      induced PCD. Cells growing attached to flasks appear to be relatively more
      resistant than suspension-growing cells in spite of endogenous bcl-2, bax, or bcl
      x levels. Furthermore, we demonstrate that interference with attachment status
      alters the sensitivity of cells to TPT-induced PCD. Although cell attachment to
      ProNectin F confers protection against TPT-induced chromatin condensation and
      cleavage of PARP, cell detachment by poly(2-hydroxyethyl methacrylate) stimulates
      TPT-induced PCD and PARP cleavage.

PMID- 9187116
TI  - Extracellular factor(s) following exposure to alpha particles can cause sister
      chromatid exchanges in normal human cells.
AB  - The mechanism(s) by which alpha particles like those emitted from inhaled radon
      and radon progeny cause their mutagenic and carcinogenic effects remains unclear.
      Although direct nuclear traversals by alpha particles may be involved in
      mediating these outcomes, increasing evidence indicates that alpha particles can
      cause alterations in DNA in the absence of direct "hits" to cell nuclei. Using
      the occurrence of excessive sister chromatid exchanges (SCEs) as an index of DNA
      damage in human lung fibroblasts, we investigated the hypothesis that alpha
      particles may induce DNA damage via the generation of extracellular factors. We
      have found that a relatively low dose of alpha particles indeed results in the
      generation of extracellular factors, which, upon transfer to unexposed normal
      human cells, can cause excessive SCEs to an extent equivalent to that observed
      when the cells are directly irradiated with the same irradiation dose. A short
      lived, SCE-inducing factor(s) was generated in alpha-irradiated culture medium
      containing serum in the absence of cells; it was found that the activity of this
      factor can be promptly inhibited by superoxide dismutase. A more persistent SCE
      inducing factor(s), which can survive freeze-thawing, is heat labile and also can
      be inhibited by superoxide dismutase, was produced by fibroblasts after exposure
      to alpha particles. These results indicate that the initiating target for alpha
      particle-induced genetic changes can be larger than the nuclear compartment alone
      and even larger than the cytoplasmic compartment. How transmissible factors like
      those observed here in vitro may extend to the in vivo condition in the context
      of alpha-particle-induced carcinogenesis in the respiratory tract and elsewhere
      remains to be determined.

PMID- 9187117
TI  - Studies on the metabolism of the novel antitumor agent [N-methyl-11C]N-[2
      (dimethylamino)ethyl]acridine-4-carboxamide in rats and humans prior to phase I
      clinical trials.
AB  - This study reports on the biodistribution and metabolism of the 11C-labeled novel
      antitumor agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) (also
      known as NSC 601316) in rats (plasma and tissues) and humans (plasma).
      Information on plasma metabolites was uniquely obtained in humans prior to Phase
      I clinical trial following i.v. injection of [11C]DACA at tracer dose. DACA was
      labeled in the N-methyl position using no-carrier-added [11C]iodomethane. Rapid
      high-performance liquid chromatography methods were developed for metabolite
      analysis of [11C]DACA. The metabolism of [11C]DACA was investigated in patients
      by plasma sampling. The biodistribution and metabolism of [11C]DACA was
      investigated in rats by plasma sampling, sacrifice experiments with tissue
      analyses, and imaging using positron emission tomography scanning. Analysis of
      human plasma demonstrated rapid and extensive metabolism of [11C]DACA. The levels
      of [11C]DACA changed from 77 +/- 8% (SD) at 5 min to 25 +/- 5% at 45 min
      postinjection. Seven radioactive metabolites were observed in human plasma, and
      one was identified as [11C]DACA-N-oxide. Rapid clearance of 11C radioactivity
      from rat blood, plasma, and major organs was observed. The half-life of 11C
      radioactivity clearance in rat blood between 15 and 90 min was calculated to be
      3.2 h; the levels of [11C]DACA in rat plasma decreased from 69 +/- 3% (SD) at 2
      min to 29 +/- 1.5% at 25 min. The number of radioactive metabolites in rat plasma
      was the same as in human plasma except that the proportions differed. Again, one
      metabolite was identified as the [11C]DACA-N-oxide. Analysis of rat tissues
      showed rapid and extensive metabolism in tissues, particularly liver and kidney;
      however, [11C]DACA (i.e., the parent compound) was the major radioactive
      component in the lung, heart, and brain over 40 min. Positron emission tomography
      scanning using [11C]DACA in the rat showed little retention of 11C radioactivity
      in major organs with rapid excretion via gut and kidney. The rat data were
      consistent with animal (mouse and rat) preclinical data obtained with preexisting
      techniques with longer-lived isotopes. Labeling of potential anticancer drugs
      with positron-emitting radionuclides and performing in vivo preclinical
      evaluation at tracer doses in animals and humans prior to Phase I clinical trials
      provides unique information that could speed up the assessment of the drug and
      could potentially assist drug development programs. In this example, there was no
      unexpected interspecies difference in metabolism of DACA that would have alerted
      us to make a change in the planned Phase I study.

PMID- 9187118
TI  - Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled
      monoclonal antibody A33) with chemotherapy (fluorouracil).
AB  - Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon
      cancer and normal colon epithelial cells. An earlier Phase I trial of 131I
      labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose
      limiting toxicity, and although modest antitumor effects were seen, no normal
      colon toxicity was observed. In this study, a nude mouse model was used to test
      whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5
      fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the
      antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5
      FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days
      1 and 5. In assessing the reduction in tumor volumes over the first 28 days of
      the experiment, 5-FU treatment (with or without leucovorin) in combination with
      131I-mAb A33 showed a statistically significant additive antitumor effect
      compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival
      was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were
      disease free at 276 days compared to none from any other group, suggesting a
      synergistic effect. These data indicate that Phase II clinical trials combining
      radiolabeled antibody therapy with 5-FU-based treatments are warranted.

PMID- 9187119
TI  - Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding
      protein-derived macrophage activating factor.
AB  - Vitamin D3-binding protein (DBP; human DBP is known as Gc protein) is the
      precursor of macrophage activating factor (MAF). Treatment of mouse DBP with
      immobilized beta-galactosidase or treatment of human Gc protein with immobilized
      beta-galactosidase and sialidase generated a remarkably potent MAF, termed DBPMAF
      or GcMAF, respectively. The domain of Gc protein responsible for macrophage
      activation was cloned and enzymatically converted to the cloned MAF, designated
      CdMAF. In Ehrlich ascites tumor-bearing mice, tumor-specific serum alpha-N
      acetylgalactosaminidase (NaGalase) activity increased linearly with time as the
      transplanted tumor cells grew in the peritoneal cavity. Therapeutic effects of
      DBPMAF, GcMAF, and CdMAF on mice bearing Ehrlich ascites tumor were assessed by
      survival time, the total tumor cell count in the peritoneal cavity, and serum
      NaGalase activity. Mice that received a single administration of DBPMAF or GcMAF
      (100 pg/mouse) on the same day after transplantation of tumor (1 x 10(5) cells)
      showed a mean survival time of 35 +/- 4 days, whereas tumor-bearing controls had
      a mean survival time of 16 +/- 2 days. When mice received the second DBPMAF or
      GcMAF administration at day 4, they survived more than 50 days. Mice that
      received two DBPMAF administrations, at days 4 and 8 after transplantation of 1 x
      10(5) tumor cells, survived up to 32 +/- 4 days. At day 4 posttransplantation,
      the total tumor cell count in the peritoneal cavity was approximately 5 x 10(5)
      cells. Mice that received two DBPMAF administrations, at days 0 and 4 after
      transplantation of 5 x 10(5) tumor cells, also survived up to 32 +/- 4 days,
      while control mice that received the 5 x 10(5) ascites tumor cells only survived
      for 14 +/- 2 days. Four DBPMAF, GcMAF, or CdMAF administrations to mice
      transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals
      showed an extended survival of at least 90 days and an insignificantly low serum
      NaGalase level between days 30 and 90.

PMID- 9187121
TI  - Efficacy of hyperthermia and polyunsaturated fatty acids on experimental
      carcinoma.
AB  - We investigated the efficacy of hyperthermia and gamma-linolenic acid on
      experimental carcinoma. This study focused on polyunsaturated fatty acids that
      are substrates for free radical reactions. Oleic acid, linolenic acid, alpha
      linolenic acid, or gamma-linolenic acid was injected into the arteries feeding
      AH109A carcinoma implanted into rat hind limbs. Among these, gamma-linolenic acid
      had the greatest effect on tumor tissue lipid peroxidation and demonstrated an
      antitumor effect. Consequently, gamma-linolenic acid injection into the feeding
      artery of a tumor was performed immediately prior to hyperthermia. This
      combination therapy induced a high level of lipid peroxidation in tumor tissue
      and a significant antitumor effect. Hyperthermia combined with gamma-linolenic
      acid produces free radical reactions by increasing the radical reaction substrate
      and may be an effective anticancer modality.

PMID- 9187120
TI  - Overexpression of p21waf1 leads to increased inhibition of E2F-1 phosphorylation
      and sensitivity to anticancer drugs in retinoblastoma-negative human sarcoma
      cells.
AB  - The effect of overexpression of p21waf1 on drug sensitivity was studied in an
      osteosarcoma cell line (SaOs-2) lacking both p53 and functional retinoblastoma
      protein using a tetracycline (TC)-inducible expression system. p21waf1 expression
      was barely detectable in SaOS-2 cells incubated in the presence of TC. After TC
      withdrawal, high levels of p21waf1 were induced in these cells. These p21waf1
      induced cells showed increased sensitivity to doxorubicin, tomudex, and
      methotrexate as compared to uninduced cells; this condition is associated with
      increased apoptosis. Expression of p21waf1 reduced cyclin A-associated kinase
      activity and, surprisingly, resulted in inhibition of phosphorylation of E2F-1
      and increased E2F-1 binding activity. An S-G2 cell cycle arrest/delay and an
      increase in expression of E2F-responsive genes (dihydrofolate reductase and
      thymidylate synthase) was correspondingly observed. Overexpression of p21waf1 in
      cells lacking functional retinoblastoma protein may mediate sensitivity to
      anticancer drugs by inhibiting E2F-1 phosphorylation, which may contribute to
      increased S-G2 cell cycle delay and increased cell susceptibility to apoptosis.

PMID- 9187123
TI  - Selective up-regulation of protein kinase C eta in phorbol ester-sensitive versus
      -resistant EL4 mouse thymoma cells.
AB  - Stimulation of sensitive EL4 mouse thymoma cells (s-EL4) with phorbol esters
      results in production of interleukin 2 (IL-2), adherence to a plastic substrate,
      and growth inhibition, whereas a phorbol ester-resistant variant (r-EL4) fails to
      respond. Previous studies revealed substantially decreased expression of protein
      kinase C (PKC) epsilon in the r-EL4 versus s-EL4 cells. This work has been
      extended to examine the more recently described PKC isozymes. Western and
      Northern analyses revealed a marked decrease in PKC eta and theta in r-EL4 as
      compared to s-EL4 cells. Treatment of these lines with phorbol ester for 24 h
      resulted in down-regulation of all PKC isozymes examined except PKC eta, which
      was up-regulated in the s-EL4 cells at the time of maximal IL-2 production. Two
      newly isolated EL4 clones, resistant to phorbol ester-induced growth inhibition
      but still exhibiting the phorbol ester-induced adherence and IL-2 production,
      both expressed PKC eta and theta. Collectively, these observations suggest a
      dissociation of growth inhibition from adherence and IL-2 production pathways and
      a potential role for PKC eta in the latter.

PMID- 9187122
TI  - Induction of apoptosis and inhibition of small cell lung cancer growth by the
      quinoxaline tyrphostins.
AB  - Coexpression of the Kit receptor tyrosine kinase and its ligand, stem cell factor
      (SCF), occurs in a high proportion of small cell lung cancers (SCLCs) and drives
      an autocrine loop that enhances proliferation. To determine whether this
      autocrine loop affects apoptosis, SCLC cells expressing only SCF or both SCF and
      Kit were deprived of growth factors for 72 h and the relative number of cells
      undergoing apoptosis was assessed using nuclear DNA content and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. Coexpression
      of SCF and Kit inhibited apoptosis; apoptosis could, in turn, be enhanced by the
      addition of the quinoxaline tyrosine kinase inhibitors, which are specific
      antagonists of the platelet-derived growth factor receptor and Kit. Treatment of
      the H526 cell line, which is growth-stimulated by soluble SCF, with AG1296
      resulted in a marked decrease in growth and an increase in apoptosis in a dose
      dependent fashion. Growth inhibition correlated well with the inhibition of Kit
      tyrosine phosphorylation. The AG1296 compound at its maximum soluble
      concentration inhibited the growth of 5 of 6 SCLC cell lines in complete medium
      by an average of 50%. These data suggest that optimized pharmacological
      inhibitors of Kit activity may be a new class of compounds potentially useful in
      the treatment of SCLC.

PMID- 9187124
TI  - Enhanced induction of very late antigen 4/lymphocyte function-associated antigen
      1-dependent T-cell migration to tumor sites following administration of
      interleukin 12.
AB  - Administration of interleukin 12 (IL-12) into mice bearing CSA1M, OV-HM, Meth A,
      or MCH-1-A1 tumor induced complete regression of CSA1M and OV-HM tumors but
      induced only a slight growth inhibition of Meth A and MCH-1-A1 tumors. These
      effects of IL-12 were associated with high and only marginal levels of T-cell
      infiltration into CSA1M/OV-HM and Meth A/MCH-1-A1 tumor masses, respectively.
      Here, we investigated the role of IL-12 in the induction of T-cell migration.
      Spleen cells from untreated or IL-12-treated CSA1M-bearing mice were stained in
      vitro with a fluorescein chemical and transferred i.v. into IL-12-untreated CSA1M
      bearing mice. Migration of donor cells was quantitated by counting the number of
      fluorescent cells on cryostat sections of tumor masses. Although only a slight
      migration was detected for spleen cells from IL-12-untreated CSA1M-bearing as
      well as IL-12-treated or untreated normal mice, enhanced migration was observed
      for cells from IL-12-treated CSA1M-bearing mice. A similar enhanced migration was
      observed for the OV-HM model. In contrast, such an enhancement was only marginal
      in the Meth A and MCH-1-A1 models. Immunohistochemical studies of tumors from IL
      12-treated mice revealed that the predominant T-cell subset was CD4+ in CSA1M and
      CD8+ in OV-HM tumor masses. Consistent with this observation, the dominant subset
      of migrating T cells was found to be CD4+ in the CSA1M and CD8+ in the OV-HM
      models. T-cell migration was inhibited by pretreatment of recipients with either
      combination of anti-very late antigen 4 + anti-vascular cell adhesion molecule 1
      or anti-lymphocyte function-associated antigen 1 + anti-intercellular adhesion
      molecule 1 monoclonal antibody. These results indicate that IL-12 can confer T
      cells with a capacity to migrate to tumor sites through very late antigen
      4/lymphocyte function-associated antigen 1 adhesion pathways and that the in vivo
      acquisition of such a capacity following IL-12 treatment correlates with the
      induction of tumor regression.

PMID- 9187125
TI  - Oncostatin M-mediated transcriptional suppression of the c-myc gene in breast
      cancer cells.
AB  - Oncostatin M (OM) inhibits proliferation of H3922, a human breast cancer cell
      line derived from a ductal infiltrating carcinoma. We have found that treatment
      of H3922 cells with OM for 72 h lowers the steady-state level of c-myc mRNA to
      16% of that seen in control cells. Our present study showed that down-regulation
      of c-myc mRNA levels was both dose and time dependent. Results from nuclear run
      off analysis and mRNA stability studies established that a major component of the
      observed OM-induced down-regulation of c-myc mRNA occurs at the transcriptional
      level. OM treatment of H3922 cells reduced the abundance of actively transcribed
      c-myc mRNAs to approximately 25% of that observed in control cells. These data
      were supported by our finding that OM did not significantly affect the half-life
      of c-myc mRNA in actinomycin-treated H3922 cells. Taken together, these data
      demonstrate that the suppressive effect of OM on c-myc gene expression in H3922
      cells occurs at the transcriptional level.

PMID- 9187126
TI  - Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors.
AB  - The retinoblastoma gene (Rb) is one of the best characterized tumor suppressor
      genes, and its inactivation is associated with a number of cancers. Previous
      studies have shown, by restriction enzyme analysis, that the promoter region of
      the Rb gene is methylated in a significant proportion of primary retinoblastoma
      tumors. We now report the first detailed methylation sequence analysis of the CpG
      island spanning the retinoblastoma promoter from hypermethylated retinoblastoma
      tumors. Our results show methylation is not confined to a specific CpG site, as
      detected by restriction enzyme studies, but extends to essentially all 27 CpG
      dinucleotides spanning the retinoblastoma CpG island, including the core
      promoter. The methylation pattern from each tumor DNA sample is different,
      ranging from densely to sparsely methylated profiles. Single CpG sites, in
      particular the E2F transcription factor binding site, as well as blocks of CpGs,
      were undermethylated in some tumor samples. Possible interference of methylation
      could be due to the binding of sequence-specific protein factors at these sites
      in the tumor cells. This study highlights that the dynamics of DNA methylation in
      cancer cells are clearly different from normal cells and gives an insight into
      the mechanism of abnormal methylation of CpG islands in cancer cells.

PMID- 9187127
TI  - Allelic deletions on chromosome 11q13 in multiple endocrine neoplasia type 1
      associated and sporadic gastrinomas and pancreatic endocrine tumors.
AB  - Endocrine tumors (ETs) of pancreas and duodenum occur sporadically and as a part
      of multiple endocrine neoplasia type 1 (MEN1). The MEN1 tumor suppressor gene has
      been localized to chromosome 11q13 by linkage analysis but has not yet isolated.
      Previous allelic deletion studies in enteropancreatic ETs suggested MEN1 gene
      involvement in tumorigenesis of familial pancreatic ETs (nongastrinomas) and
      sporadic gastrinomas. However, only a few MEN1-associated duodenal gastrinomas
      and sporadic pancreatic nongastrinomas have been investigated. We used tissue
      microdissection to analyze 95 archival pancreatic and duodenal ETs and metastases
      from 50 patients for loss of heterozygosity (LOH) on 11q13 with 10 polymorphic
      markers spanning the area of the putative MEN1 gene. Chromosome 11q13 LOH was
      detected in 23 of 27 (85%) MEN1-associated pancreatic ETs (nongastrinomas), 14 of
      34 (41%) MEN1-associated gastrinomas, 3 of 16 (19%) sporadic insulinomas, and 8
      of 18 (44%) sporadic gastrinomas. Analysis of LOH on 11q13 showed different
      deletion patterns in ETs from different MEN1 patients and in multiple tumors from
      individual MEN1 patients. The present results suggest that the MEN1 gene plays a
      role in all four tumor types. The lower rate of 11q13 LOH in MEN1-associated and
      sporadic gastrinomas and sporadic insulinomas as compared to MEN1 nongastrinomas
      may reflect alternative genetic pathways for the development of these tumors or
      mechanisms of the MEN1 gene inactivation that do not involve large deletions. The
      isolation of the MEN1 gene is necessary to further define its role in
      pathogenesis of pancreatic and duodenal ETs.

PMID- 9187128
TI  - Involvement of the Fanconi's anemia protein FAC in a pathway that signals to the
      cyclin B/cdc2 kinase.
AB  - Lymphoblastoid cell lines derived from patients with the chromosomal instability
      disorder Fanconi's anemia (FA) are hyperresponsive to G2 delay and apoptosis
      induced by cross-linking agents such as mitomycin C (MMC). Here, we investigated
      whether the protein defective in FA complementation group C (FA-C) cells
      functions in a pathway that signals to the cdc2 kinase complex, which controls
      mitotic progression. FA-C lymphoblasts treated with a low dose of MMC (1-5
      microM, 1 h) exhibited a protracted G2-M arrest and subsequent apoptosis by 2
      days after treatment. This G2-M arrest was mediated by persistent inactivation of
      the cyclin B1/cdc2 kinase complex characterized by both sustained accumulation of
      cyclin B1 and tyrosine phosphorylation of cdc2. In phenotypically corrected (wild
      type) cells, the same treatment induced only temporal G2-M arrest, associated
      with a transient inactivation of the cyclin B1/cdc2 kinase complex, after which
      cells resumed cycling. Treatment with higher dosages (15-30 microM, 1 h) resulted
      in S-phase arrest and induced a similar high level of apoptosis in FA-C and wild
      type cells, accompanied by degradation of cyclin B1 and dephosphorylation of
      cdc2. In low-dose treated G2-M-arrested FA-C cells, caffeine-dependent activation
      of cdc2 released the G2-M block but failed to protect against apoptosis,
      suggesting that apoptosis was not a direct consequence of persistent cdc2 kinase
      inactivation. Thus, at low doses of MMC, FA-C cells exhibit a unique cyclin
      B1/cdc2 response that is not observed in wild-type cells treated with an
      equitoxic high dosage of cross-linker. Although these results do not necessarily
      implicate a role for FAC in regulating cyclin B/cdc2 kinase activity, available
      evidence suggests that the FAC protein is involved in a cross-link damage
      avoidance pathway that signals to this kinase complex.

PMID- 9187129
TI  - Effect of mimosine on DNA synthesis in mammalian cells.
AB  - We have designed a general protocol to assess the rate of replicon initiation in
      mammalian cells in the presence of inhibitors of DNA synthesis. It is based on
      cross-linking DNA in vivo with trioxsalen, which effectively blocks the movement
      of the replication forks along DNA, while having little effect on initiation of
      replication. We applied this protocol to study the effect of the plant amino acid
      mimosine on the rate of replicon initiation in exponentially growing murine
      erythroleukemia F4N cells. We found out that during the first 2 h after
      application of 25-400 microM mimosine, the initiation step was inhibited more
      efficiently than the overall DNA synthesis. In this respect, the effect of
      mimosine was similar to that of gamma-ray irradiation and differed from that of
      hydroxyurea and aphidicolin. The results suggest that in addition to inhibiting
      the elongation step of DNA synthesis, mimosine inhibits the initiation of DNA
      replication as well.

PMID- 9187130
TI  - FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic
      bronchial lesions and are associated with cancer-related FHIT cDNA splicing
      aberrations.
AB  - We evaluated primary lung cancers, tumor cell lines, and preneoplastic bronchial
      lesions for molecular genetic abnormalities in the candidate tumor suppressor
      gene FHIT, which spans the FRA3B fragile site at 3p14.2. 3p14.2 allele loss was
      very frequent in 32 lung cancer cell lines [100% of small cell lung cancer and
      88% of non-small cell lung cancer (NSCLC)] and 108 primary NSCLC cancers (45%),
      with numerous breakpoints indicating involvement of several distinct regions in
      the FRA3B site. 3p14 allele loss was least frequent in the adenocarcinoma subtype
      and occurred at the relatively late carcinoma in situ stage of preneoplastic
      bronchial lesions found in NSCLC patients. Homozygous deletions within the
      FHIT/FRA3B region were found in 6 of 135 (4.4%) thoracic cancer cell lines.
      Northern blot showed low or absent FHIT expression in most thoracic cancer cell
      lines tested, whereas reverse transcription-PCR showed that 59-62% exhibited
      aberrant FHIT transcripts but nearly always (93-100%) also expressing the wild
      type transcripts. Aberrant transcripts included precise deletions of FHIT exons,
      insertion of non-FHIT sequences between exons and insertions replacing exons.
      Complete open reading frame single-strand conformational polymorphism analysis of
      102 lung cancer cDNAs revealed only one nonsplicing mutation. Normal cells
      including bronchial epithelium, lung, and trachea expressed wild-type FHIT
      transcript and a variant transcript deleted for exon 8 but not the other aberrant
      transcripts, arguing against exon 8-deleted FHIT transcripts being tumor
      specific. Our findings support the conclusion that FHIT/FRA3B abnormalities are
      associated with lung cancer pathogenesis but that FHIT abnormalities differ from
      the types of mutations and lack of wild-type transcript found in classic tumor
      suppressor genes, and functional studies are needed to define the role of FHIT in
      thoracic tumorigenesis.

PMID- 9187131
TI  - Activating mutations in the N- and K-ras oncogenes differentially affect the
      growth properties of the IL-6-dependent myeloma cell line ANBL6.
AB  - Although the underlying genetic defect in multiple myeloma is unknown, activating
      mutations in the N- and K-ras oncogenes are common. Recent studies have suggested
      that ras mutations are associated with disease progression. We have introduced an
      activated N-ras12, N-ras61, or K-ras12 cDNA into the interleukin 6 (IL-6)
      dependent multiple myeloma cell line ANBL6 to determine the effect of N- and K
      ras on the growth/death properties of ANBL6. All three transduced cell
      populations demonstrate a growth advantage over the parent ANBL6 when propagated
      on normal human bone marrow stromal cells. In the absence of bone marrow stromal
      cells, augmentation of growth was observed in all three mutant ras-expressing
      populations at optimal and suboptimal concentrations of IL-6. Furthermore, in the
      absence of IL-6, all mutant ras populations demonstrated an augmentation in DNA
      synthesis when compared to the parent ANBL6. However, growth of the K-ras12
      population in the absence of IL-6 was significantly inhibited when compared to
      the mutant N-ras populations. This could be explained by the observation that in
      the absence of IL-6, N-ras12 and N-ras61 suppress apoptosis, whereas K-ras12 does
      not. We also found that mutant ras expression could result in early protection
      from glucocorticoid-induced apoptosis similar to that observed by the addition of
      IL-6. However, the combination of mutant ras and IL-6 could completely block the
      glucocorticoid induction of apoptosis in long-term cultures. These data suggest
      that mutations in different ras family members may have similar or distinct
      effects on myeloma tumor growth and death and may alter the response to
      glucocorticoid treatment.

PMID- 9187132
TI  - Misexpression of disrupted HMGI architectural factors activates alternative
      pathways of tumorigenesis.
AB  - Cancer arises from aberrations in the genetic mechanisms that control growth and
      differentiation. HMGI-C and HMGI(Y) are members of the HMGI family of
      architectural factors expressed in embryonic or undifferentiated cells and highly
      associated with transformation. Translocations of 12q13-15 in lipomas (fat cell
      tumors) disrupt HMGI-C and fuse its DNA-binding domains to novel transcriptional
      regulatory domains. This study shows that in a rare, karyotypically distinct
      group of human lipomas, rearrangements of 6p21-23 produce internal deletions
      within HMGI(Y). Activation of the rearranged alleles leads to expression of
      aberrant HMGI(Y) transcripts in differentiated adipocytes. A molecular analysis
      of these transcripts demonstrates that fusion of HMGI DNA-binding domains to
      putative transcriptional regulatory domains was not necessary for lipoma
      formation. However, such fusions may facilitate tumor development because
      activation of the wild-type HMGI allele, normally required for tumorigenesis, is
      bypassed in lipomas which express chimeric HMGI proteins. We hypothesize that
      HMGI misexpression in a differentiated cell is a pivotal event in benign
      tumorigenesis, and the molecular pathway of tumor development depends upon the
      precise nature of HMGI disruption.

PMID- 9187133
TI  - Regulation of CD44v6-containing isoforms during proliferation of normal and
      malignant epithelial cells.
AB  - CD44 is a family of molecules involved in cell-cell and cell-matrix interactions.
      Various isoforms of CD44 arise by insertion of one or more of the variant exons
      into the common backbone shared by all forms of CD44. In this work, we studied
      the expression of CD44 and exon v6-containing CD44 isoforms (CD44v6) in several
      nonmalignant and malignant conditions and the possibilities for regulating the
      expression of CD44v6. In primary squamocellular carcinomas of the head and neck,
      CD44 and CD44v6 were down-regulated in poorly differentiated tumors, whereas
      these molecules were uniformly expressed in the normal squamocellular epithelium,
      in proliferating skin diseases, and in nonmalignant tumors. When CD44v6
      expression of original tumors and that of squamocellular carcinoma cell lines
      derived from them were compared, no CD44v6 up-regulation could be observed on in
      vitro growing cells. Moreover, several regulators were unable to up-regulate
      CD44v6 expression on cultured cell lines in vitro. When the same cell lines
      formed tumors after s.c. injection into severe combined immunodeficient mice,
      some of them up-regulated their CD44v6 expression. These data suggest that cell
      lines at certain differentiation stages can be induced to express CD44v6. Our
      results further indicate that CD44v6 positivity cannot be used as a universal
      indicator of tumor metastasis. Instead, the down-regulation of CD44v6 in
      squamocellular tumors is a sign of malignant transformation of the epithelium.

PMID- 9187134
TI  - Amplification of the genes BCHE and SLC2A2 in 40% of squamous cell carcinoma of
      the lung.
AB  - Gene amplification is a common genetic change in human cancer cells. Previously,
      we provided the first evidence for gene amplification at chromosome band 3q26 in
      squamous cell lung carcinoma. In this study, the following analyses were
      performed: (a) we evaluated biopsies and paraffin-embedded tissues of 16
      additional squamous cell lung carcinomas for gene amplification using reverse
      chromosome painting. Of the 16 tumors, 3 tumors showed an amplification of the
      entire long arm of chromosome 3, and 3 tumors showed various amplifications on
      3q, all of which involved chromosome band 3q26; (b) we tested eight genes
      encompassing region 3q25-qter in two different tumors to identify amplified genes
      on chromosome 3q. The genes SI, BCHE, and SLC2A2 were amplified in both tumors;
      and (c) we analyzed 15 additional paraffin-embedded tissues to determine the
      amplification frequency of these genes. Of the 15 squamous cell lung carcinomas,
      6 showed amplification for at least 1 of the genes, with BCHE and SLC2A2 as the
      genes most frequently amplified. Together, our reverse chromosome painting data
      and our PCR analysis indicate gene amplification at 3q26 in 40% of all squamous
      cell lung carcinomas with BCHE and SLC2A2 as possible target genes of the
      amplification unit in squamous cell lung carcinoma.

PMID- 9187135
TI  - Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth
      and metastasis.
AB  - The cell surface adhesion molecule MCAM (MUC18) is strongly expressed by advanced
      primary and metastatic melanomas but is weaker and less frequent in nevus cells.
      Previous studies have shown that MCAM expression correlates with tumor thickness
      and metastatic potential of human melanoma cells in nude mice. To provide direct
      evidence that MCAM plays a role in tumor growth and metastasis of human melanoma,
      the nonmetastatic MCAM-negative primary cutaneous melanoma SB-2 cells were
      transfected with MCAM cDNA and analyzed subsequently for changes in their
      tumorigenic and metastatic potential. Enforced expression of MCAM in SB-2 cells
      rendered them highly tumorigenic and increased their metastatic potential in nude
      mice as compared with parental and control transfected cells. The transfected
      cells displayed increased homotypic adhesion, increased attachment to human
      endothelial cells, decreased ability to adhere to laminin, and increased
      invasiveness through Matrigel-coated filters. Anti-MCAM monoclonal antibody
      reversed these functions in the transfected cells but not in control cells. The
      above changes in function attributed to the expression of MCAM may underlie the
      contribution of MCAM/MUC18 to the malignant phenotype.

PMID- 9187136
TI  - Reexpression of the major protein kinase C substrate, SSeCKS, suppresses v-src
      induced morphological transformation and tumorigenesis.
AB  - SSeCKS (pronounced essex) encodes a major protein kinase C substrate, the
      expression of which is down-regulated in src- and ras-transformed rodent
      fibroblasts but not in raf-transformed rodent fibroblasts (X. Lin et al., Mol.
      Cell. Biol., 15: 2754-2762, 1995). Using a panel of ras-transformed or revertant
      Rat-6 cells that exhibit selective parameters of transformation, we show that
      down-regulation of SSeCKS correlates with anchorage-independent growth.
      Cotransfection of NIH3T3 fibroblasts with an SSeCKS expression plasmid decreased
      6-30-fold the ability of a v-src expressor plasmid to induce colonies in soft
      agar. To differentiate between possible tumor suppressive or growth-inhibitory
      effects of SSeCKS, we developed conditionally transformed cell lines (expressing
      ts72v-src) with tetracycline-regulated SSeCKS expression. SSeCKS suppressed the
      ability of v-src to induce increased cellular refractility, focus formation, soft
      agar colony formation, in vitro invasiveness in Matrigel, and growth in low serum
      (0.5%) but did not inhibit cell proliferation in high serum (10%) at the
      permissive (35 degrees C) temperature for src kinase activity. However, at the
      nonpermissive (39.5 degrees C) temperature, SSeCKS induced growth arrest. SSeCKS
      expression did not affect: (a) the protein level, in vivo or in vitro kinase
      activity of ts72src; (b) the activity of jun NH2-terminal kinase; and (c) the
      level of mitogen-activated protein kinase (extracellular signal-regulated kinase
      2) protein. However, extracellular signal-regulated kinase 2 activity was induced
      5-10-fold by SSeCKS in the presence of active src. SSeCKS reversed the ability of
      v-src to decrease the formation of vinculin-associated adhesion plaques, actin
      based stress fibers, and filopodia structures. These data suggest a tumor
      suppressive role for SSeCKS via the control of cytoskeletal architecture and cell
      signaling.

PMID- 9187137
TI  - M. Stephen Meyn, ataxia telangiectasia and cellular responses to DNA damage.
      Cancer Res., 55:5991-6001, 1995.

PMID- 9187138
TI  - Fashioning the vertebrate heart: earliest embryonic decisions.
AB  - Our goal here is to set out the types of unitary decisions made by heart
      progenitor cells, from their appearance in the heart field until they form the
      simple heart tube. This provides a context to evaluate cell fate, lineage and,
      finally, morphogenetic decisions that configure global heart form and function.
      Some paradigms for cellular differentiation and for pattern generation may be
      borrowed from invertebrates, but neither Drosophila nor Caenorhabditis elegans
      suffice to unravel higher order decisions. Genetic analyses in mouse and
      zebrafish may provide one entrance to these pathways.

PMID- 9187139
TI  - Requirements of DFR1/Heartless, a mesoderm-specific Drosophila FGF-receptor, for
      the formation of heart, visceral and somatic muscles, and ensheathing of
      longitudinal axon tracts in CNS.
AB  - DFR1 encodes a mesoderm-specific fibroblast growth factor receptor in Drosophila.
      Here, we identified and characterized a protein-null mutant of DFR1 and examined
      DFR1 expression in embryos using anti-DFR1 antibody. Mutant phenotypes were
      completely rescued by a genomic fragment from the DFR1 locus. After invagination,
      mesodermal cells expressing DFR1 undergo proliferation and spread out dorsally to
      form a monolayer beneath the ectoderm. In mutant embryos, however, the mesoderm
      is not capable of extending to the normal dorsal limit and consequently
      mesodermal cells fail to receive ectodermal signals and thus rendered incapable
      of differentiating into primordia for the heart, visceral and somatic muscles.
      DFR1 is also required for normal development of the central nervous system. The
      absence of DFR1 resulted in the failure of longitudinal glia to enwrap
      longitudinal axon tracts. DFR1 mutant phenotypes were partially mimicked by the
      targeted expression of activated Yan, thus demonstrating the MAP kinase pathway
      to be involved in differentiation of mesoderm.

PMID- 9187140
TI  - Control of germ-band retraction in Drosophila by the zinc-finger protein
      HINDSIGHT.
AB  - Drosophila embryos lacking hindsight gene function have a normal body plan and
      undergo normal germ-band extension. However, they fail to retract their germ
      bands. hindsight encodes a large nuclear protein of 1920 amino acids that
      contains fourteen C2H2-type zinc fingers, and glutamine-rich and proline-rich
      domains, suggesting that it functions as a transcription factor. Initial
      embryonic expression of hindsight RNA and protein occurs in the endoderm (midgut)
      and extraembryonic membrane (amnioserosa) prior to germ-band extension and
      continues in these tissues beyond the completion of germ-band retraction.
      Expression also occurs in the developing tracheal system, central and peripheral
      nervous systems, and the ureter of the Malpighian tubules. Strikingly, hindsight
      is not expressed in the epidermal ectoderm which is the tissue that undergoes the
      cell shape changes and movements during germ-band retraction. The embryonic
      midgut can be eliminated without affecting germ-band retraction. However,
      elimination of the amnioserosa results in the failure of germ-band retraction,
      implicating amnioserosal expression of hindsight as crucial for this process.
      Ubiquitous expression of hindsight in the early embryo rescues germ-band
      retraction without producing dominant gain-of-function defects, suggesting that
      hindsight's role in germ-band retraction is permissive rather than instructive.
      Previous analyses have shown that hindsight is required for maintenance of the
      differentiated amnioserosa (Frank, L. C. and Rushlow, C. (1996) Development 122,
      1343-1352). Two classes of models are consistent with the present data. First,
      hindsight's function in germ-band retraction may be limited to maintenance of the
      amnioserosa which then plays a physical role in the retraction process through
      contact with cells of the epidermal ectoderm. Second, hindsight might function
      both to maintain the amnioserosa and to regulate chemical signaling from the
      amnioserosa to the epidermal ectoderm, thus coordinating the cell shape changes
      and movements that drive germ-band retraction.

PMID- 9187141
TI  - Hedgehog organises the pattern and polarity of epidermal cells in the Drosophila
      abdomen.
AB  - The abdomen of adult Drosophila, like that of other insects, is formed by a
      continuous epithelium spanning several segments. Each segment is subdivided into
      an anterior (A) and posterior (P) compartment, distinguished by activity of the
      selector gene engrailed (en) in P but not A compartment cells. Here we provide
      evidence that Hedgehog (Hh), a protein secreted by P compartment cells, spreads
      into each A compartment across the anterior and the posterior boundaries to form
      opposing concentration gradients that organize cell pattern and polarity. We find
      that anteriorly and posteriorly situated cells within the A compartment respond
      in distinct ways to Hh: they express different combinations of genes and form
      different cell types. They also form polarised structures that, in the anterior
      part, point down the Hh gradient and, in the posterior part, point up the
      gradient - therefore all structures point posteriorly. Finally, we show that
      ectopic Hh can induce cells in the middle of each A compartment to activate en.
      Where this happens, A compartment cells are transformed into an ectopic P
      compartment and reorganise pattern and polarity both within and around the
      transformed tissue. Many of these results are unexpected and lead us to reassess
      the role of gradients and compartments in patterning insect segments.

PMID- 9187142
TI  - Hedgehog acts by distinct gradient and signal relay mechanisms to organise cell
      type and cell polarity in the Drosophila abdomen.
AB  - The epidermis of the adult Drosophila abdomen is formed by a chain of anterior
      (A) and posterior (P) compartments, each segment comprising one A and one P
      compartment. In the accompanying paper (Struhl et al., 1997), we provide evidence
      that Hedgehog protein (Hh), being secreted from P compartment cells, organises
      the pattern and polarity of A compartment cells. Here we test whether Hh acts
      directly or by a signal relay mechanism. We use mutations in Protein Kinase A
      (PKA) or smoothened (smo) to activate or to block Hh signal transduction in
      clones of A compartment cells. For cell type, a scalar property, both
      manipulations cause strictly autonomous transformations: the cells affected are
      exactly those and only those that are mutant. Hence, we infer that Hh acts
      directly on A compartment cells to specify the various types of cuticular
      structures that they differentiate. By contrast, these same manipulations cause
      non-autonomous effects on cell polarity, a vectorial property. Consequently, we
      surmise that Hh influences cell polarity indirectly, possibly by inducing other
      signalling factors. Finally, we present evidence that Hh does not polarise
      abdominal cells by utilising either Decapentaplegic (Dpp) or Wingless (Wg), the
      two morphogens through which Hh acts during limb development. We conclude that,
      in the abdomen, cell type and cell polarity reflect distinct outputs of Hh
      signalling and propose that these outputs are controlled by separable gradient
      and signal relay mechanisms.

PMID- 9187143
TI  - The NIMA-related kinase 2, Nek2, is expressed in specific stages of the meiotic
      cell cycle and associates with meiotic chromosomes.
AB  - The Aspergillus nimA gene encodes a Ser/Thr protein kinase which is required for
      mitosis, in addition to Cdc2, and which has been suggested to have a role in
      chromosomal condensation. In this study, we isolated a potential murine homologue
      of nimA, Nek2, which was shown to be expressed most abundantly in the testis of
      the adult tissues examined. Its expression in the testis was restricted to the
      germ cells, with highest levels detected in spermatocytes at pachytene and
      diplotene stages. Immunohistochemical analysis revealed that Nek2 localized to
      nuclei, exhibiting a non-uniform distribution within the nucleus. Nek2 appeared
      to be associated with meiotic chromosomes, an association that was better defined
      by immunolocalization to hypotonically dispersed meiotic chromosomes. This
      localization was more apparent in regions of dense chromatin, including the sex
      vesicle, and was also obvious at some of the chromosome ends. The presence of
      Nek2 protein was not unique to male germ cells, as it was found in meiotic
      pachytene stage oocytes as well. Furthermore, in an in vitro experimental setting
      in which meiotic chromosome condensation was induced with okadaic acid, a
      concomitant induction of Nek2 kinase activity was observed. The expression of
      Nek2 in meiotic prophase is consistent with the hypothesis that in vivo, Nek2 is
      involved in the G2/M phase transition of the cell cycle. Our results further
      provide evidence that in vivo, mouse Nek2 is involved in events of meiosis,
      including but not limited to chromosomal condensation.

PMID- 9187144
TI  - A C. elegans E/Daughterless bHLH protein marks neuronal but not striated muscle
      development.
AB  - The E proteins of mammals, and the related Daughterless (DA) protein of
      Drosophila, are ubiquitously expressed helix-loop-helix (HLH) transcription
      factors that play a role in many developmental processes. We report here the
      characterization of a related C. elegans protein, CeE/DA, which has a dynamic and
      restricted distribution during development. CeE/DA is present embryonically in
      neuronal precursors, some of which are marked by promoter activity of a newly
      described Achaete-scute-like gene hlh-3. In contrast, we have been unable to
      detect CeE/DA in CeMyoD-positive striated muscle cells. In vitro gel mobility
      shift analysis detects dimerization of CeE/DA with HLH-3 while efficient
      interaction of CeE/DA with CeMyoD is not seen. These studies suggest multiple
      roles for CeE/DA in C. elegans development and provide evidence that both common
      and alternative strategies have evolved for the use of related HLH proteins in
      controlling cell fates in different species.

PMID- 9187145
TI  - Transcriptionally repressed germ cells lack a subpopulation of phosphorylated RNA
      polymerase II in early embryos of Caenorhabditis elegans and Drosophila
      melanogaster.
AB  - Early embryonic germ cells in C. elegans and D. melanogaster fail to express many
      messenger RNAs expressed in somatic cells. In contrast, we find that ribosomal
      RNAs are expressed in both cell types. We show that this deficiency in mRNA
      production correlates with the absence of a specific phosphoepitope on the
      carboxy-terminal domain of RNA polymerase II. In both C. elegans and Drosophila
      embryos, this phosphoepitope appears in somatic nuclei coincident with the onset
      of embryonic transcription, but remains absent from germ cells until these cells
      associate with the gut primordium during gastrulation. In contrast, a second
      distinct RNA polymerase II phosphoepitope is present continuously in both somatic
      and germ cells. The germ-line-specific factor PIE-1 is required to block mRNA
      production in the germ lineage of early C. elegans embryos (Seydoux, G., Mello,
      C. C., Pettitt, J., Wood, W. B., Priess, J. R. and Fire, A. (1996) Nature 382,
      713-716). We show here that PIE-1 is also required for the germ-line-specific
      pattern of RNA polymerase II phosphorylation. These observations link inhibition
      of mRNA production in embryonic germ cells to a specific modification in the
      phosphorylation pattern of RNA polymerase II and suggest that repression of RNA
      polymerase II activity may be part of an evolutionarily conserved mechanism that
      distinguishes germ line from soma during early embryogenesis. In addition, these
      studies also suggest that different phosphorylated isoforms of RNA polymerase II
      perform distinct functions.

PMID- 9187146
TI  - Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development.
AB  - Bone Morphogenetic Proteins (BMPs) play crucial roles in a variety of
      developmental processes, but their functions during early vertebrate brain
      development are largely unknown. To investigate this problem, we have compared by
      in situ hybridization the expression of five Bmp genes belonging to the
      Drosophila Decapentaplegic (Bmp2 and Bmp4) and 60A subgroups (Bmp5, Bmp6 and
      Bmp7). Striking co-expression of these Bmps is observed within the dorsomedial
      telencephalon, coincident with a future site of choroid plexus development. Bmp
      co-expression overlaps that of Msx1 and Hfh4, and is complementary to that of
      Bf1. The domain of Bmp co-expression is also associated with limited growth of
      the neuroectoderm, as revealed by morphological observation, reduced cell
      proliferation, and increased local programmed cell death. In vitro experiments
      using explants from the embryonic lateral telencephalic neuroectoderm reveal that
      exogenous BMP proteins (BMP4 and BMP2) induce expression of Msx1 and inhibit Bf1
      expression, a finding consistent with their specific expression patterns in vivo.
      Moreover, BMP proteins locally inhibit cell proliferation and increase apoptosis
      in the explants. These results provide evidence that BMPs function during
      regional morphogenesis of the dorsal telencephalon by regulating specific gene
      expression, cell proliferation and local cell death.

PMID- 9187147
TI  - The allocation of early blastomeres to the ectoderm and endoderm is variable in
      the sea urchin embryo.
AB  - During sea urchin development, a tier-to-tier progression of cell signaling
      events is thought to segregate the early blastomeres to five different cell
      lineages by the 60-cell stage (E. H. Davidson, 1989, Development 105, 421-445).
      For example, the sixth equatorial cleavage produces two tiers of sister cells
      called 'veg1' and 'veg2,' which were projected by early studies to be allocated
      to the ectoderm and endoderm, respectively. Recent in vitro studies have proposed
      that the segregation of veg1 and veg2 cells to distinct fates involves signaling
      between the veg1 and veg2 tiers (O. Khaner and F. Wilt, 1991, Development 112,
      881-890). However, fate-mapping studies on 60-cell stage embryos have not been
      performed with modern lineage tracers, and cell interactions between veg1 and
      veg2 cells have not been shown in vivo. Therefore, as an initial step towards
      examining how archenteron precursors are specified, a clonal analysis of veg1 and
      veg2 cells was performed using the lipophilic dye, DiI(C16), in the sea urchin
      species, Lytechinus variegatus. Both veg1 and veg2 descendants form archenteron
      tissues, revealing that the ectoderm and endoderm are not segregated at the sixth
      cleavage. Also, this division does not demarcate cell type boundaries within the
      endoderm, because both veg1 and veg2 descendants make an overlapping range of
      endodermal cell types. The allocation of veg1 cells to ectoderm and endoderm
      during cleavage is variable, as revealed by both the failure of veg1 descendants
      labeled at the eighth equatorial division to segregate predictably to either
      tissue and the large differences in the numbers of veg1 descendants that
      contribute to the ectoderm. Furthermore, DiI-labeled mesomeres of 32-cell stage
      embryos also contribute to the endoderm at a low frequency. These results show
      that the prospective archenteron is produced by a larger population of cleavage
      stage blastomeres than believed previously. The segregation of veg1 cells to the
      ectoderm and endoderm occurs relatively late during development and is
      unpredictable, indicating that later cell position is more important than the
      early cleavage pattern in determining ectodermal and archenteron cell fates.

PMID- 9187148
TI  - Analysis of competence and of Brachyury autoinduction by use of hormone-inducible
      Xbra.
AB  - Analysis of gene function in Xenopus development frequently involves over
      expression experiments, in which RNA encoding the protein of interest is
      microinjected into the early embryo. By taking advantage of the fate map of
      Xenopus, it is possible to direct expression of the protein to particular regions
      of the embryo, but it has not been possible to exert control over the timing of
      expression; the protein is translated immediately after injection. To overcome
      this problem in our analysis of the role of Brachyury in Xenopus development, we
      have, like Kolm and Sive (1995; Dev. Biol. 171, 267-272), explored the use of
      hormone-inducible constructs. Animal pole regions derived from embryos expressing
      a fusion protein (Xbra-GR) in which the Xbra open reading frame is fused to the
      ligand-binding domain of the human glucocorticoid receptor develop as atypical
      epidermis, presumably because Xbra is sequestered by the heat-shock apparatus of
      the cell. Addition of dexamethasone, which binds to the glucocorticoid receptor
      and releases Xbra, causes formation of mesoderm. We have used this approach to
      investigate the competence of animal pole explants to respond to Xbra-GR, and
      have found that competence persists until late gastrula stages, even though by
      this time animal caps have lost the ability to respond to mesoderm-inducing
      factors such as activin and FGF. In a second series of experiments, we
      demonstrate that Xbra is capable of inducing its own expression, but that this
      auto-induction requires intercellular signals and FGF signalling. Finally, we
      suggest that the use of inducible constructs may assist in the search for target
      genes of Brachyury.

PMID- 9187149
TI  - The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick
      limb bud through interaction with FGF8, an apical ectodermal factor.
AB  - Vertebrate limb formation has been known to be initiated by a factor(s) secreted
      from the lateral plate mesoderm. In this report, we provide evidence that a
      member of the fibroblast growth factor (FGF) family, FGF10, emanates from the
      prospective limb mesoderm to serve as an endogenous initiator for limb bud
      formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8
      expression in the nascent apical ectoderm. Ectopic application of FGF10 to the
      chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm,
      resulting in the formation of an additional complete limb. Expression of Fgf10
      persists in the mesenchyme of the established limb bud and appears to interact
      with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing
      activity. These results suggest that FGF10 is a key mesenchymal factor involved
      in the initial budding as well as the continuous outgrowth of vertebrate limbs.

PMID- 9187150
TI  - A family of mammalian Fringe genes implicated in boundary determination and the
      Notch pathway.
AB  - The formation of boundaries between groups of cells is a universal feature of
      metazoan development. Drosophila fringe modulates the activation of the Notch
      signal transduction pathway at the dorsal-ventral boundary of the wing imaginal
      disc. Three mammalian fringe-related family members have been cloned and
      characterized: Manic, Radical and Lunatic Fringe. Expression studies in mouse
      embryos support a conserved role for mammalian Fringe family members in
      participation in the Notch signaling pathway leading to boundary determination
      during segmentation. In mammalian cells, Drosophila fringe and the mouse Fringe
      proteins are subject to posttranslational regulation at the levels of
      differential secretion and proteolytic processing. When misexpressed in the
      developing Drosophila wing imaginal disc the mouse Fringe genes exhibit conserved
      and differential effects on boundary determination.

PMID- 9187151
TI  - Negative regulation of Armadillo, a Wingless effector in Drosophila.
AB  - Drosophila Armadillo and its vertebrate homolog beta-catenin play essential roles
      both in the transduction of Wingless/Wnt cell-cell signals and in the function of
      cell-cell adherens junctions. Wingless and Wnts direct numerous cell fate choices
      during development. We generated a mutant protein, Armadillo(S10), with a 54
      amino acid deletion in its N-terminal domain. This mutant is constitutively
      active in Wingless signaling; its activity is independent of both Wingless signal
      and endogenous wild-type Armadillo. Armadillo's role in signal transduction is
      normally negatively regulated by Zeste-white 3 kinase, which modulates Armadillo
      protein stability. Armadillo(S10) is more stable than wild-type Armadillo,
      suggesting that it is less rapidly targeted for degradation. We show that
      Armadillo(S10) has escaped from negative regulation by Zeste white-3 kinase, and
      thus accumulates outside junctions even in the absence of Wingless signal.
      Finally, we present data implicating kinases in addition to Zeste white-3 in
      Armadillo phosphorylation. We discuss two models for the negative regulation of
      Armadillo in normal development and discuss how escape from this regulation
      contributes to tumorigenesis.

PMID- 9187152
TI  - Parthenogenetic activation of mouse eggs by microinjection of a truncated c-kit
      tyrosine kinase present in spermatozoa.
AB  - A truncated form of the c-kit tyrosine kinase receptor, corresponding to the
      phosphotransferase portion of the cytoplasmic catalytic domain and the
      carboxyterminus (tr-kit), is accumulated during late mouse spermiogenesis. Here
      we report that tr-kit is specifically localized in the residual sperm cytoplasm,
      with maximal accumulation in the midpiece of the flagellum, suggesting that it
      can enter the egg during fertilization. Microinjection of extracts from COS cells
      expressing a recombinant tr-kit protein into metaphase II-arrested mouse oocytes
      caused complete oocyte activation, including cortical granule exocytosis,
      completion of the 2nd meiotic division, formation of a parthenogenetic pronucleus
      and progression through cleavage stages. No activation above background levels
      was obtained with extracts from mock-transfected COS cells. Similar results were
      obtained by microinjection of in vitro synthesized tr-kit mRNA into metaphase II
      arrested oocytes. Tr-kit-induced parthenogenetic egg activation was completely
      inhibited by oocyte preincubation with the Ca2(+)-chelating agent BAPTA-AM or
      with a specific inhibitor of phospholipase C activity. Tr-kit-induced egg
      activation was associated with a decrease in activity of mitogen-activated
      protein kinase, an essential component of the cytostatic factor. These results
      candidate tr-kit as a putative sperm factor required for triggering activation of
      mouse eggs at fertilization.

PMID- 9187153
TI  - Zfx mutation results in small animal size and reduced germ cell number in male
      and female mice.
AB  - The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y
      chromosomes, have been speculated to function in sex differentiation,
      spermatogenesis, and Turner syndrome. We derived Zfx mutant mice by targeted
      mutagenesis. Mutant mice (both males and females) were smaller, less viable, and
      had fewer germ cells than wild-type mice, features also found in human females
      with an XO karyotype (Turner syndrome). Mutant XY animals were fully
      masculinized, with testes and male genitalia, and were fertile, but sperm counts
      were reduced by one half. Homozygous mutant XX animals were fully feminized, with
      ovaries and female genitalia, but showed a shortage of oocytes resulting in
      diminished fertility and shortened reproductive lifespan, as in premature ovarian
      failure in humans. The number of primordial germ cells was reduced in both XX and
      XY mutant animals at embryonic day 11.5, prior to gonadal sex differentiation.
      Zfx mutant animals exhibited a growth deficit evident at embryonic day 12.5,
      which persisted throughout postnatal life and was not complemented by the Zfy
      genes. These phenotypes provide the first direct evidence for a role of Zfx in
      growth and reproductive development.

PMID- 9187154
TI  - www.journal?

PMID- 9187155
TI  - Downsizing competence: the myth of quality or let the barber do the surgery.

PMID- 9187156
TI  - New technology in the treatment of an old disease.

PMID- 9187157
TI  - Noninvasive positive pressure ventilation: a positive view in need of supportive
      evidence.

PMID- 9187158
TI  - Noninvasive ventilation: a welcome resurgence and a plea for caution.

PMID- 9187159
TI  - Airway exchange catheters for safe extubation: the clinical and scientific
      details that make the concept work.

PMID- 9187160
TI  - What's new in staging of lung cancer?

PMID- 9187161
TI  - Prevalence of sleep-disordered breathing in diastolic heart failure.
AB  - OBJECTIVE: Sleep-disordered breathing (SDB) is common in congestive heart
      failure. While isolated diastolic heart failure (DHF) accounts for up to a third
      of all cases of congestive heart failure, the prevalence of SDB in DHF is
      unknown. We aim to determine the prevalence and characteristics of SDB in a group
      of patients with symptomatic DHF. METHODS: Twenty subjects with symptomatic DHF
      (New York Heart Association class II or III) and isolated diastolic dysfunction
      on echocardiography were assessed with lung function tests, modified sleep and
      health questionnaire, and overnight polysomnography. Significant SDB was defined
      as an apnea/hypopnea index (AHI) > 10. RESULTS: Thirteen female and seven male
      subjects (mean age, 65+/-6.0 years; mean body mass index (BMI), 28+/-3.2) were
      evaluated, of whom 17 (85%) had a diagnosis of hypertension. Overall sleep
      quality was poor, with fragmentation and frequent arousals associated with
      respiratory events. Fifty-five percent of the patients had significant SDB,
      mainly obstructive apneas. BMI and the prevalence of hypertension were similar in
      patients with and without SDB. The deceleration time, an index of diastolic
      dysfunction, was more prolonged in the group with SDB (236+/-40 ms vs 282+/-31
      ms; p<0.05). As a group, a lower minimum percentage arterial oxygen saturation
      during sleep, but not the AHI was associated with more severe degree of diastolic
      dysfunction on echocardiogram, including a lower ratio between the early peak
      transmittal flow velocity and the late peak atrial systolic velocity (rho=0.57;
      p<0.05) and a prolonged isovolumic relaxation time (rho=-0.54; p<0.05).
      CONCLUSIONS: SDB is common in patients with DHF. Patients with DHF and SDB may be
      associated with worse diastolic dysfunction than those without SDB, although a
      causal relationship remains to be established.

PMID- 9187162
TI  - The sleep/wake habits of patients diagnosed as having obstructive sleep apnea.
AB  - STUDY OBJECTIVE: To determine the sleep/wake habits of patients diagnosed as
      having obstructive sleep apnea (ie, respiratory event index [REI] > or = 5).
      DESIGN: Case series with prospective data collection to determine the
      relationship among sleepiness, REI, and sleep/wake habits. Patients were grouped
      according to their multiple sleep latency test (MSLT) results (< or = 5 and > 5)
      and REI (mild REI < or = 20; moderate REI > 20 but < or = 60; and severe REI >
      60). SETTING: An American Sleep Disorders Association-accredited sleep
      laboratory. PATIENTS: Three hundred ninety (325 male, 65 female) consecutive
      patients seen between June 1993 and January 1995 for evaluation of sleep apnea.
      This included a sleep, medical, and psychiatric evaluation followed by a physical
      examination. Sleep histories and sleep/wake habits were recorded by a physician
      trained in sleep medicine. Polysomnographic evaluation consisted of a nocturnal
      clinical polysomnogram (CPSG) and an MSLT on the following day. Of 390 patients,
      268 completed polysomnographic evaluation (CPSG and MSLT). MEASUREMENTS AND
      RESULTS: Sleepy (MSLT < or = 5) patients with mild (REI < or = 20) and moderate
      apnea (REI > 20 < or = 60) reported spending significantly less time in bed than
      sleepy patients with severe apnea (REI > 60). Those with severe apnea (REI > 60)
      reported napping significantly more and experienced a more severe disruption of
      their routine daily activities because of sleepiness when compared with mild and
      moderate OSA patients. CONCLUSIONS: These data suggest that sleep habits have an
      important modulatory effect on the level of sleepiness and this effect is lost as
      the severity of sleep-disordered breathing increases.

PMID- 9187163
TI  - Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea.
AB  - BACKGROUND: Upper airway inflammation is present in patients with obstructive
      sleep apnea (OSA). OBJECTIVE: To determine whether exhaled pentane and nitric
      oxide (NO) levels, two nonspecific markers of inflammation, are increased in
      patients with OSA. METHODS: Exhaled nasal and oral pentane and NO levels were
      determined before and after sleep in 20 patients with OSA (apnea-hypopnea index,
      48+/-7; mean+/-SEM) and eight healthy control subjects. RESULTS: In patients with
      OSA, exhaled nasal and oral pentane levels after sleep were significantly higher
      than presleep values (6.1+/-1.2 nM vs 3.4+/-0.4 nM, and 7.0+/-1.3 nM vs 4.2+/-0.4
      nM, respectively; p<0.05). Likewise, exhaled nasal and oral NO levels after sleep
      were significantly higher than presleep values in patients with OSA (39.7+/-3.8
      ppb vs 28.4+/-2.9 ppb and 10.9+/-1.5 ppb vs 6.6+/-0.8 ppb, respectively; p<0.05).
      By contrast, there were no significant differences in exhaled nasal and oral
      pentane, and nasal NO levels before and after sleep in control subjects. Exhaled
      oral NO levels were significantly increased after sleep in comparison to presleep
      values in control subjects (p<0.05). CONCLUSION: Exhaled nasal pentane and NO
      levels are increased after sleep in patients with moderate-severe OSA. These data
      suggest that upper airway inflammation is present in these patients after sleep.

PMID- 9187164
TI  - Ultrasonic nebulization of albuterol is no more effective than jet nebulization
      for the treatment of acute asthma in children.
AB  - STUDY OBJECTIVE: Nebulizer systems used to generate therapeutic aerosols vary in
      their ability to deliver medication to the airway. In a recent study in 17 adults
      with stable asthma, albuterol given using an ultrasonic nebulizer (UN) appeared
      to produce greater bronchodilatation than the same dose of albuterol given by a
      jet nebulizer (JN). The purpose of this study was to determine if the UN used in
      that study would produce a better bronchodilator response in children with acute
      asthma than the JN system that has been in use at Cardinal Glennon Children's
      Hospital. DESIGN: Randomized, prospective, unblinded study. SETTING: An urban
      university children's hospital emergency department. PARTICIPANTS: One hundred
      thirteen children, aged 7 to 16 years, who presented for treatment of acute
      moderately severe asthma completed this study. INTERVENTIONS: After randomization
      and exclusion of dropouts, 46 children received albuterol by UN and 67 were
      treated by JN. MEASUREMENTS: Pulmonary function tests (PFTs) by spirometry, pulse
      oximetry, and symptom score at baseline and at 15 and 30 min following a single
      prescribed treatment. RESULTS: PFT on entry to the study was the same in both
      groups (FEV1; p>0.97). The change in FEV1 after therapy (UN+0.22 L vs JN+0.37 L)
      was significant (p<0.05) and favored JN. There was no difference in the
      improvement in pulmonary function between JN and UN therapy in children with an
      initial FEV1/FVC > 75% predicted but when FEV1/FVC < 75%, the improvement in FEV1
      again favored the JN (UN+0.2 vs JN+0.47; p<0.05). CONCLUSION: For the treatment
      of acute exacerbations of asthma in children, there is no greater bronchodilator
      response when albuterol is administered by a UN than by a JN.

PMID- 9187165
TI  - The effects of the combination of inhaled ipratropium and oral theophylline in
      asthma.
AB  - BACKGROUND: In comparison to beta-agonist drugs, which are the primary
      bronchodilator drugs in current use in asthma, both oral theophylline and inhaled
      ipratropium have a weaker bronchodilating action in asthma. Although a number of
      studies have shown an additive effect of ipratropium in combination with beta
      agonist bronchodilator drugs in asthmatics, to our knowledge, the effects of
      combined treatment with ipratropium and theophylline have not been assessed.
      STUDY OBJECTIVE: To assess whether the combination of oral theophylline and
      inhaled ipratropium has an additive bronchodilator effect in asthmatics. DESIGN:
      Double-blind, placebo-controlled, crossover study. SUBJECTS: Nineteen patients (8
      male, 11 female) with mild-to-moderate stable asthma. METHODS: Initially the
      optimal single oral dose of theophylline required to achieve therapeutic blood
      levels (10 to 20 microg/mL) was established in each patient. They then returned
      at varying intervals on 4 subsequent days. On each day, they received, in a
      random, placebo-controlled, double-blind, crossover design, one of four different
      therapies: oral and inhaled placebo; oral theophylline at the established optimal
      dose (range, 300 to 700 mg) plus inhaled placebo; oral placebo plus inhaled (40
      microg) ipratropium; and the combination of theophylline and ipratropium.
      Spirometry was performed at baseline and at 15 min, 30 min, and hourly intervals
      for 6 h after therapy. RESULTS: Each drug regimen resulted in a significant
      (p<0.05) increase in FEV1, but the combined regimen resulted in a significantly
      greater bronchodilation (p<0.05) over either ipratropium or theophylline alone
      (FEV1=3.00+/-0.75 L vs 2.48+/-0.77 L vs 2.61+/-0.72 L, respectively, at 3 h
      postdrug). CONCLUSIONS: There was a significant, early, sustained additive
      bronchodilator effect of the combination therapy; there were no untoward side
      effects. These findings indicate that the addition of inhaled ipratropium to oral
      theophylline provides greater bronchodilation than either drug alone and may be a
      useful therapeutic modality in asthma.

PMID- 9187166
TI  - Effects of inhaled albuterol and ipratropium bromide on autonomic control of the
      cardiovascular system.
AB  - STUDY OBJECTIVE: Systemic administration of beta-agonist and anticholinergic
      drugs markedly impair normal autonomic heart rate control. The purpose of this
      study was to quantify and compare the effects of therapeutic doses of inhaled
      albuterol and ipratropium on autonomic control of the cardiovascular system.
      DESIGN: Randomized, double-blind, placebo-controlled, crossover design study.
      SETTING: Tertiary-care hospital. SUBJECTS: Twelve healthy male volunteers.
      INTERVENTIONS: Subjects self-administered four puffs through a spacer device from
      one of three identical inhalers containing albuterol (100 microg per puff),
      ipratropium (20 microg per puff), or placebo in three different testing sessions.
      MEASUREMENTS: ECG and noninvasive continuous BP traces were recorded at baseline
      and from 45 to 75 min after administration of the drug. Autonomic control of the
      cardiovascular system was quantified by analysis of spontaneous baroreflex
      sensitivity and power spectral analysis of heart rate variability. RESULTS:
      Neither albuterol nor ipratropium caused a significant alteration in baroreflex
      sensitivity, normalized low-power frequency, or normalized high-power frequency.
      No adverse effects were reported by subjects. CONCLUSIONS: Inhalation of four
      puffs of albuterol (400 microg) or ipratropium (80 microg) does not alter the
      autonomic control of the cardiovascular system in young, healthy male subjects.

PMID- 9187167
TI  - Measurement of respiratory resistance in the emergency department: feasibility in
      young children with acute asthma.
AB  - OBJECTIVES: To assess, in acutely ill asthmatic children, the feasibility of
      obtaining reproducible measurements of two independent lung function tests,
      namely spirometry and respiratory resistance, using the forced oscillation
      technique (Rfo). DESIGN/SETTING: A prospective observational study of 150
      previously untrained children, aged 2 to 17 years, treated for acute asthma in a
      tertiary-care pediatric emergency department. MEASUREMENTS: Following a
      standardized physical examination, three measurements of respiratory resistance
      by forced oscillation were attempted at 8 Hz (Rfo8) and at 16 Hz (Rfo16),
      followed by spirometry, all using the same instrument (Custo Vit R; Custo Med;
      Munich, Germany). RESULTS: On the initial assessment, 98 (65%) children, aged 2
      to 17 years, were able to reproducibly perform the Rfo8 measurement, 77 (51%)
      were able to reproducibly perform the Rfo16 measurement, while only 65 (43%)
      subjects managed to reliably perform spirometry. A notable proportion of
      preschool-aged children cooperated with the Rfo8 technique: 19% of 3-year-olds,
      40% of 4-year-olds, and 83% of 5-year-olds. The superior success rate with Rfo8
      as compared with spirometry was seen in all age groups but was most striking both
      in preschoolers (relative risk [RR]=10.5; 95% confidence interval [CI], 8.0 to
      13.8) and in children aged 6 to 9 years (RR= 1.28; 95% CI, 1.18 to 1.39). Rfo8
      values correlated significantly with clinical markers of asthma severity such as
      respiratory rate (r=0.38) and heart rate (r=0.23) as well as with FEV1 values
      (r2=0.73). CONCLUSIONS: This study demonstrates the feasibility of obtaining
      reproducible measurements of respiratory resistance in a notable proportion of
      untrained, acutely ill, asthmatic children. The forced oscillation technique
      appears as an attractive alternative to objectively assess lung function in
      children too young or too ill to cooperate with spirometry.

PMID- 9187168
TI  - Weight gain and longitudinal changes in lung function in steel workers.
AB  - Associations among dust exposure, smoking habits, and demographic factors and
      longitudinal changes of lung function were assessed among male steel workers.
      Cohort descriptive data analysis was conducted in 541 steel workers who had
      performed spirometry at least twice between 1982 and 1991 (mean follow-up, 6.1
      years). The annual change (slope) in FVC, FEV1, FEV1/FVC%, and in body weight was
      determined by simple linear regression. The Pearson correlation coefficient
      between weight change and spirometry changes was calculated. Comparisons were
      also done in 75 pairs of steel workers matched by age, height, initial FEV1, and
      smoking status, but whose FEV1 declines differed by > or = 60 mL/yr. The FEV1 and
      FVC declined an average of 44 and 50 mL/yr, respectively, for the cohort as a
      whole. The FEV1 and FVC declined 52 and 54 mL/yr for current smokers, 43 and 53
      mL/yr for ex-smokers, and 36 and 43 mL/yr for nonsmokers, respectively.
      Increasing weight was highly correlated with accelerated decline in lung function
      (p<0.0001). In the matched pairs, mean slopes for FVC, FEV1, and FEV1/FVC ratio
      were -96 mL/yr, -95 mL/yr, and -0.40%/yr for the rapid decliners; and +5 mL/yr,
      +10 mL/yr, and +0.10%/yr for their partners (p<0.0001). Matched pair comparisons
      showed that the rapid decliners averaged a 4.313 kg weight gain, while their
      partners gained 1.044 kg during the follow-up period. The slope of weight gain
      was 0.708 kg/yr for rapid decliners and 0.191 kg/yr for comparison workers
      (p<0.0036). Weight gain, in addition to aging and cigarette smoking, was found to
      be associated with the longitudinal rate of decline in FVC, FEV1, and FEV1/FVC
      ratio.

PMID- 9187169
TI  - Detection of small airway dysfunction using specific airway conductance.
AB  - STUDY OBJECTIVE: To assess the potential utility of specific airway conductance
      (sGaw) in detecting small airways dysfunction, the postlung-transplant
      bronchiolitis obliterans syndrome (BOS) was used as a model of small airways
      dysfunction. BOS is defined as an otherwise unexplained 20% reduction in FEV1. We
      hypothesized that if sGaw is sensitive to small airways dysfunction, it should
      decrease before the decline in FEV1. DESIGN/METHODS: The pulmonary function test
      and sGaw measurements of patients who underwent heart-lung or bilateral lung
      transplantation between May 1981 and January 1993 were reviewed. Patients with
      and without BOS were identified. A significant decrease in sGaw was defined as a
      20% fall from baseline. RESULTS: Twenty-six BOS and 15 non-BOS patients had at
      least three sGaw measurements such that trends could be examined. Eleven of the
      26 BOS patients (42%) had a significant decrease in sGaw before a 20% decrease in
      FEV1, as compared to 2 of the 15 non-BOS patients (13%) (p=0.08). In comparison,
      12 of the 26 BOS patients (46%) and 4 of the 15 non-BOS patients (27%) had a
      significant decrease in forced expiratory flow at 25 to 75% of the forced lung
      volume (FEF(25-75)) (p=0.32), an accepted test of small airways dysfunction.
      CONCLUSION: sGaw tended to decrease before FEV1 in BOS. The trend in sGaw was
      similar to the trend in FEF(25-75). We conclude that (1) small airways may
      contribute more to airway conductance than previously thought, and (2) further
      prospective studies are warranted to better define the relative contribution of
      small and large airways to sGaw.

PMID- 9187170
TI  - Preoperative spirometry and laparotomy: blowing away dollars.
AB  - STUDY OBJECTIVE: Increasing evidence indicates that routine preoperative
      diagnostic spirometry (pulmonary function tests [PFTs]) before elective abdominal
      surgery does not predict individual risk of postoperative pulmonary complications
      and is overutilized. This economic evaluation estimates potential savings from
      reduced use of preoperative PFTs. DESIGN: Analyses of (1) real costs (resource
      consumption to perform tests) and (2) reimbursements (expenditures for charges)
      by third-party payers. SETTING: University-affiliated public and Veterans Affairs
      hospitals. PATIENTS: Adults undergoing elective abdominal operations.
      MEASUREMENTS AND RESULTS: Average real cost of PFTs was $19.07 (95% confidence
      interval [CI], $18.53 to $19.61), based on a time and motion study. Average
      reimbursement expenditure by third-party payers for PFTs was $85 (range, $33 to
      $150; 95% CI, $68 to $103), based on Medicare payment of $52 and a survey of nine
      urban US hospitals with a spectrum of bed sizes and teaching status. Estimates
      from published literature included the following: (1) annual number of major
      abdominal operations, 3.5 million; and (2) proportion of PFTs not meeting current
      guidelines, 39% (95% CI, 0.31 to 0.47). Local data were used when estimates were
      not available in the literature: (1) proportion of laparotomies that are
      elective, 76% (95% CI, 0.73 to 0.79); and (2) frequency of PFTs before
      laparotomy, 69% (95% CI, 0.54 to 0.84). Estimated annual national real costs for
      preoperative PFTs are $25 million to $45 million. If use of PFTs were reduced by
      our estimate for the proportion of PFTs not meeting current guidelines, potential
      annual national cost savings would be $7,925,411 to $21,406,707. National
      reimbursement expenditures by third-party payers range from more than $90 million
      to more than $235 million. If use were reduced, potential annual savings in
      reimbursements would be $29,084,076 to $111,345,440. Potential savings to
      Medicare approach $8 million to $20 million annually. CONCLUSION: Reduced use of
      PFTs before elective abdominal surgery could generate substantial savings.
      Current evidence indicates reduced use would not compromise patients' outcomes.

PMID- 9187171
TI  - Perfusion lung scintigraphy for the prediction of postlobectomy residual
      pulmonary function.
AB  - STUDY OBJECTIVES: Scintigraphic prediction of the residual pulmonary function
      following a lobectomy is not widely employed; its accuracy is poorly known. This
      study aims at determining the accuracy and the clinical value of the
      scintigraphic prediction of postlobectomy residual function. PATIENTS AND
      INTERVENTIONS: In this study, 41 patients with bronchial carcinoma underwent a
      perfusion lung scintigraphy before lobectomy; the functional contribution of each
      single lobe was computed by an indirect method proposed by Wernly et al.; the
      results of the scintigraphic prediction were compared with those of the pulmonary
      function tests performed 1 month after surgery. MEASUREMENTS AND RESULTS: The
      linear regression analyses of predicted and observed values of FVC and FEV1
      showed significant correlations (R2=0.607 and 0.749, respectively); however, an
      evident scatter of data was obtained, as quantified by the values of imprecision
      (20.70% and 18.11%, respectively) and global inaccuracy (25.50% and 22.90%,
      respectively). The estimates of both FVC and FEV1 were significantly better in
      right lung lobectomies than in left lung lobectomies (mean imprecision and global
      inaccuracy: 15.43% and 14.94% for the right lung, and 27.27% and 29.00% for the
      left lung). CONCLUSIONS: The scintigraphic prediction of postlobectomy residual
      function is easily implemented by the method herein employed; it has a greater
      margin of uncertainty than that of pneumonectomy, especially for left
      lobectomies; however, the use of some safety thresholds for predicted values of
      FEV1 (1.2 L for upper lobectomies and 1 L for lower lobectomies) guarantees a
      safe clinical use of the test.

PMID- 9187172
TI  - A randomized trial of empyema therapy.
AB  - STUDY OBJECTIVES: To determine the optimal treatment of empyema thoracis (within
      the fibrinopurulent phase of illness) comparing pleural drainage and fibrinolytic
      therapy vs video-assisted thoracoscopic surgery (VATS), with regard to efficacy
      and duration of hospitalization. DESIGN: Twenty patients with confirmed
      parapneumonic empyema thoracis were randomized to chest tube pleural drainage
      plus streptokinase (CT-SK) vs VATS. SETTING: University-based teaching hospital
      providing for Dallas County. PATIENTS AND METHODS: Equivalent groups of patients
      with parapneumonic empyema thoracis were randomized to receive either of two
      therapies: CT-SK (n=9) or VATS (n=11). Outcomes analysis with respect to
      treatment efficacy, hospital duration, chest tube duration, hospital costs, and
      need for subsequent procedures was performed. RESULTS: Each group suffered one
      mortality (p=not significant). When compared with the CT-SK group, the VATS group
      had a significantly higher primary treatment success [10/11, 91% vs 4/9, 44%;
      p<0.05 Fisher's Exact Test], lower chest tube duration (5.8+/-1.1 vs 9.8+/-1.3
      days; p=0.03), and lower number of total hospital days (8.7+/-0.9 vs 12.8+/-1.1
      days; p=0.009). Clinically relevant but not statistically significant differences
      in hospital costs ($16,642+/-2,841 vs $24,052+/-3,466, p=0.11) also favored the
      VATS group. Of note, all the CT-SK treatment failures could be salvaged with
      VATS, and none required thoracotomy. CONCLUSIONS: In patients with loculated,
      complex fibrinopurulent parapneumonic empyema thoracis, a primary treatment
      strategy of VATS is associated with a higher efficacy, shorter hospital duration,
      and less cost than a treatment strategy that utilizes catheter-directed
      fibrinolytic therapy.

PMID- 9187173
TI  - Lung volume reduction surgery at a community hospital: program development and
      outcomes.
AB  - STUDY OBJECTIVES: Description of the development and results of a program in lung
      volume reduction surgery (LVRS) at a community hospital. DESIGN: Prospective data
      collection. SETTING: A 320-bed community hospital. PATIENTS: Fifty-five patients
      consecutively discharged from the hospital following LVRS. The mean preoperative
      FEV1 averaged 28% (+/-8%) of predicted values, while the preoperative PaCO2
      averaged 49 mm Hg (+/-11.5 mm Hg). Forty-eight patients completed a preoperative
      conditioning regimen and underwent the procedure on an elective basis. Seven
      patients underwent the procedure during a hospital admission for a COPD
      exacerbation. Eight patients required mechanical ventilation preoperatively,
      including three who had required long-term mechanical ventilatory support.
      RESULTS: Three patients (5%) died in the hospital following surgery. One patient
      developed chronic ventilator dependence. All three of the patients who required
      long-term mechanical ventilation preoperatively were weaned from the ventilator
      and returned home. Follow-up pulmonary function testing is available for 42
      patients 3 months after surgery, and for 20 patients 6 months after the
      operation. At 3 months, the mean FEV1 improved 0.19 L (p=0.0002), the mean
      improvement for FVC was 0.37 L (p=0.0001), and the mean drop in residual volume
      was 0.97 L (p=0.0001). Similar changes are seen at 6 months. Highly significant
      improvements were also seen in quality of life measurements and exercise
      performance. The benefits of surgical treatment of emphysema seemed similar in
      both elective and urgent groups. CONCLUSIONS: LVRS can be done safely and
      effectively at a community hospital, with significant improvement in pulmonary
      function and quality of life.

PMID- 9187174
TI  - Median fibrillation frequency in cardiac surgery: influence of temperature and
      guide to countershock therapy.
AB  - OBJECTIVE: This study was designed (1) to investigate the effects of normothermic
      and hypothermic perfusion on the median frequency of the fibrillating myocardium,
      and (2) to elucidate whether frequency-guided countershock therapy improves
      countershock success during the reperfusion phase of cardiac surgery. DESIGN:
      Prospective, randomized study. SETTING: University hospital cardiac surgery room.
      PATIENTS: Thirty patients (first part of the study) and 38 patients (second part
      of the study) scheduled for elective coronary artery bypass surgery. METHODS AND
      RESULTS: During cardiopulmonary bypass, ventricular fibrillation (VF) was induced
      at a core body temperature of 34.1+/-0.2 degrees C (normothermia) (n=15) or at a
      core body temperature of 29.8+/-0.2 degrees C (hypothermia) (n=15). Using fast
      Fourier transformation of the ECG signal, median fibrillation frequency was
      recorded continuously for a period of 120 s. At the end of surgery, countershock
      was performed as soon as VF was recognized on the ECG monitor (X Hz group; n=19)
      or countershock was not performed until median fibrillation frequency had
      increased to the threshold of at least 5 Hz (5 Hz group; n=19). Median
      fibrillation frequency in the normothermic fibrillation group was statistically
      higher than in the hypothermic group. In the X Hz and 5 Hz countershock group,
      median fibrillation frequency before the first countershock attempt was 3.6+/-0.2
      Hz and 5.4+/-0.1 Hz (p<0.0001), respectively. In the X Hz group, six
      countershocks resulted in supraventricular rhythm, 10 in VF, two in
      electromechanical dissociation, and one in asystole. In the 5 Hz group, 16
      countershocks resulted in supraventricular rhythm, two in VF, and one in asystole
      (p=0.008). CONCLUSIONS: During normothermia, median fibrillation frequency is
      significantly higher than during hypothermic perfusion conditions. During the
      reperfusion phase of cardiac surgery, countershock success rate is significantly
      higher when a threshold of at least 5 Hz had been reached before the first
      countershock attempt.

PMID- 9187175
TI  - Erythropoietin in pediatric cardiac surgery: clinical efficacy and effective
      dose.
AB  - We assessed the clinical efficacy and determined the effective dose of
      erythropoietin (EPO) in 48 children scheduled for open heart surgery without
      blood transfusion. The children were divided into three groups: group 1 (n=21)
      was treated with 300 U/kg of EPO; group 2 (n=11) was treated with 150 U/kg of
      EPO; and group 3 (n=16) was not treated with EPO. EPO was administered on the day
      of hospital admission (6 to 7 days prior to surgery), on the following day,
      immediately after surgery, and on the following day. Immediately after surgery,
      the hemoglobin concentration in groups 1 and 2 was significantly higher than that
      in group 3. The reticulocyte count in groups 1 and 2 was significantly higher
      than that in group 3. Open heart surgery was completed without transfusion in all
      21 patients in group 1 (100%), 10 of 11 in group 2 (90.9%), and 11 of 16 in group
      3 (68.8%). EPO caused no adverse reactions. In conclusion, EPO was effective as
      an adjuvant therapy for open heart surgery without blood transfusion in children.
      Administration of a relatively high dose of EPO (300 U/kg) seems to be effective
      for pediatric patients.

PMID- 9187176
TI  - Electromyographic response to exercise in cardiac transplant patients: a new
      method for anaerobic threshold determination?
AB  - The purpose of this study was to investigate the possible use of integrated
      surface electromyography (iEMG) in cardiac transplant patients (CTPs) as a new
      noninvasive determinant of the metabolic response to exercise by studying the
      relationship between the iEMG threshold (iEMGT) and other more conventional
      methods for anaerobic threshold (AT) determination, such as the lactate threshold
      (LT) and the ventilatory threshold (VT). Thirteen patients (age: 57+/-7 years,
      mean+/-SD; height: 163+/-7 cm; body mass: 70.5+/-8.6 kg; posttransplant time:
      87+/-49 weeks) were selected as subjects. Each of them performed a ramp protocol
      on a cycle ergometer (starting at 0 W, the workload was increased in 10 W/min).
      During the tests, gas exchange data, blood lactate levels, and iEMG of the vastus
      lateralis were collected to determine VT, LT, and iEMGT, respectively. The
      results evidenced no significant difference between mean values of VT, LT, or
      iEMGT, when expressed either as oxygen uptake (11.1+/-2.4, 11.7+/-2.3, and 11.0+/
      2.8 mL/kg/min, respectively) or as percent maximum oxygen uptake (61.6+/-7.5,
      62.2+/-7.7, and 59.6+/-8.2%, respectively). In conclusion, our findings suggest
      that iEMG might be used as a complementary, noninvasive method for AT
      determination in CTPs. In addition, since the aerobic impairment of these
      patients is largely due to peripheral limitation, determination of iEMGT could be
      used to assess the effectiveness of an exercise rehabilitation program to improve
      muscle aerobic capacity in CTPs.

PMID- 9187177
TI  - High-resolution CT scan in the evaluation of exercise-induced interstitial
      pulmonary edema in cardiac patients.
AB  - OBJECTIVE: To evaluate the onset of exercise-induced interstitial pulmonary edema
      in cardiac patients by high-resolution CT (HRCT). DESIGN: Prospective, normal
      controlled. PARTICIPANTS: Thirty subjects divided into three groups: group 1--10
      outpatients with chronic congestive heart failure (CCHF), New York Heart
      Association (NYHA) class I; group 2--10 outpatients with CCHF, NYHA class II/III;
      and group 3 (control)--10 normal subjects. METHOD: HRCT scans were obtained at
      rest and 4, 8, 12, 16, and 20 min after progressive treadmill exercise test.
      RESULTS: The following HRCT findings consistent with interstitial edema were
      significantly different (p<0.05) in group 2 when compared with groups 1 and 3:
      artery/bronchus ratio > 1 in the upper lobes, peripheral increase in the vascular
      markings, interlobular septal thickening, and peribronchial "cuffing." These
      differences were maximal at 12 min after exercise and returned to normal values
      after 20 min. CONCLUSION: Interstitial pulmonary edema was present immediately
      after exercise in CCHF patients. It may be important in the genesis of dyspnea of
      these patients.

PMID- 9187178
TI  - The effect of a patient's risk-taking attitude on the cost effectiveness of
      testing strategies in the evaluation of pulmonary lesions.
AB  - STUDY OBJECTIVES: To assess the health and cost effects of a patient's risk
      taking attitudes about diagnostic tests. DESIGN: Cost-effectiveness analysis.
      SETTING: Diagnostic testing strategies used in the evaluation of a patient with a
      radiographically detected lung lesion were evaluated. Strategies included
      combinations of sputum, fine-needle aspiration, bronchoscopy, thoracoscopy, and
      expectant management. PATIENTS: Patient data were obtained from the Survival
      Epidemiology and End Results Program, MEDLINE search, National Center for Health
      Statistics, and the Universities of Iowa and Stanford, and Kaiser Permanente
      Hospital. INTERVENTIONS: Different patient risk-taking attitudes were simulated
      using decision analysis. MEASUREMENTS: Lifetime cost of medical care, life
      expectancy, and cost effectiveness. RESULTS: The cost effectiveness of competing
      strategies depended on patient attitudes about taking risks. For a patient averse
      to expectantly waiting without definitive knowledge of whether cancer was or was
      not present, testing strategies using invasive procedures, such as thoracoscopy,
      were more cost effective. In contrast, for a patient who was identical except
      that he or she was averse to tests with higher morbidity and mortality,
      strategies that involved expectantly waiting, instead of more invasive tests,
      were more cost effective. Small changes in some risk-taking attitudes resulted in
      large changes in cost effectiveness. CONCLUSIONS: Risk-taking attitudes
      influenced the cost effectiveness of testing strategies. Consideration of patient
      risk-taking attitudes in diagnostic testing appears warranted in setting clinical
      policies and making individual decisions.

PMID- 9187179
TI  - Usefulness of argyrophilic nucleolar organizer regions score to differentiate
      suspicious malignancy in pulmonary cytology.
AB  - OBJECTIVE: Pulmonary cytologic specimens reported as "suspicious for malignancy"
      pose problems in clinical management. Silver staining for argyrophilic nucleolar
      organizer regions (AgNOR) has proved useful in making a cytopathologically
      differential diagnosis between benign and malignant cells. This study aimed to
      evaluate the usefulness of AgNOR score in the diagnosis of pulmonary cytologic
      specimens deemed inconclusive by conventional staining methods. METHODS:
      Pulmonary cytologic specimens initially reported as suspicious for malignancy
      with Papanicolaou or May-Grunwald-Giemsa (MGG) staining obtained from 35 proved
      cases were destained then restained using the AgNOR technique. Another 35 cases
      with clear cytologic diagnosis were also examined for comparison. The median
      number of dots, defined as the AgNOR score, was used to differentiate malignant
      from benign specimens. RESULTS: Malignant cases had significantly higher AgNOR
      scores than benign ones (p<0.001). There were no significant differences among
      smears previously stained with Papanicolaou or MGG method, among specimens
      obtained via bronchoscopic brushing, fine-needle aspiration of lung or pleural
      effusion, or among subgroups of malignant diseases. Based on the results of our
      previous study, the cutoff value of the AgNOR score to differentiate benignancy
      from malignancy was set at 6. At this setting, the sensitivity and specificity of
      AgNOR score were 88% and 80%, respectively, in aiding a differential diagnosis of
      pulmonary cytologic specimens initially classified as suspicious for malignancy.
      For those cases with a clear cytologic diagnosis, the sensitivity and specificity
      of AgNOR score were 92% and 100%, respectively. For all cases, the sensitivity of
      AgNOR score was 90% and the specificity was also 90%. CONCLUSIONS: The AgNOR
      score is of value in aiding a differential diagnosis between benign and malignant
      lesions in pulmonary specimens with equivocal cytologic features.

PMID- 9187180
TI  - Recombinant interferon alpha-2b in the management of malignant pleural effusions.
AB  - Twenty-one patients with malignant pleural effusion (MPE) were prospectively
      entered into a nonrandomized, single-armed study to evaluate the efficacy and
      safety of recombinant interferon (IFN) alpha-2b (INTRON A; Schering-Plough;
      Kenilworth, NJ) as an intrapleural palliative agent. From March 1989 through
      February 1993 (48 months), 21 patients were entered into the study. No
      symptomatic effusion recurred and no substantial side effects were associated
      with treatment. This suggests recombinant IFN alpha-2b represents a safe and
      effective intrapleural agent for the palliation of MPE.

PMID- 9187181
TI  - Can (99m)technetium methylene diphosphonate bone scans objectively document
      costochondritis?
AB  - STUDY OBJECTIVES: To determine whether bone imaging with 99mTc methylene
      diphosphonate is a specific method of making the diagnosis of costochondritis in
      patients with chest pain who rule out for myocardial infarction. DESIGN:
      Nonblinded prospective controlled study in 20 patients and 10 control subjects.
      SETTING: Inpatient medical service of a tertiary teaching hospital. PATIENTS: Two
      hundred consenting patients admitted to the hospital with chest pain and
      suspected myocardial infarction were examined. Those in whom acute myocardial
      infarction was ruled out were evaluated for the clinical signs of
      costochondritis, ie, tenderness over one or more costochondral junctions. Twenty
      patients who met the clinical criterion gave informed consent and were subjected
      to bone imaging. Ten control subjects with cancer who did not have clinical signs
      of costochondritis underwent bone imaging to rule out metastatic disease (normal
      in all cases). INTERVENTIONS: Bone imaging with I.V. 99mTc methylene
      diphosphonate. MEASUREMENTS: Bone scans of the investigative patients and the
      control subjects were read by two independent nuclear medicine specialists.
      RESULTS: Sixteen of the 20 patients with clinically diagnosed costochondritis
      showed increased technetium uptake at all costochondral junctions bilaterally;
      six of them also had increased uptake elsewhere on the chest wall (sternum,
      manubrium, or first rib). All 10 of the control patients likewise showed
      increased technetium uptake at all costochondral junctions bilaterally.
      CONCLUSIONS: Bone imaging with 99mTc methylene diphosphonate is not a specific
      method of making the diagnosis of costochondritis.

PMID- 9187182
TI  - Factor V Leiden prevalence in venous thromboembolism patients.
AB  - BACKGROUND: Recent findings have demonstrated a high frequency of activated
      protein C resistance in patients suffering from deep venous thrombosis (DVT).
      This abnormality has been related to a mutation in the factor V gene (at
      nucleotide position 1,691, guanine to adenine [G-->A] substitution). AIM: To
      assess the frequency of the mutation in unselected inpatients with a proved DVT.
      To study the clinical characteristics of such patients. METHODS: All consecutive
      patients admitted to the hospital because of a clinical suspicion of DVT were
      eligible. Diagnosis of DVT with the help of venous ultrasound imaging or
      venography. Ventilation and perfusion lung scan was performed in all patients,
      and interpreted according to the Prospective Investigation of Pulmonary Embolism
      Diagnosis criteria; in patients with a low- or intermediate-probability lung
      scan, pulmonary angiography was requested. Polymerase chain reaction
      amplification was performed in patients with a proved DVT. A control group
      consisted of bone marrow volunteer donors. RESULTS: From July 1994 to November
      1995, 165 patients were included. Thrombosis was considered as distal in 77 and
      proximal in 88; an associated pulmonary embolism (PE) was found in 75 patients.
      Of 165 patients, 24 (14.5%) showed the factor V gene mutation (95% confidence
      interval, 9.4 to 19.8); the mutation was present in 3.5% of 200 bone marrow
      volunteer donors; odds ratio for having DVT in the presence of the mutation was
      4.1. No difference in the level of DVT, or the presence of an associated PE was
      observed according to the presence of the mutation. Patients with the mutation
      have a significantly more frequent history of DVT (p=0.04) and more previous
      reported episodes (1.1 vs 0.6; p=0.04). CONCLUSION: The factor V mutation is
      frequent in unselected DVT patients. No difference in the severity of the
      thrombosis episode was observed in these patients.

PMID- 9187183
TI  - A symptom-based measure of the severity of chronic lung disease: results from the
      Veterans Health Study.
AB  - STUDY OBJECTIVES: We developed a symptom-based measure of severity for chronic
      lung disease (CLD) that can be readily administered in ambulatory care settings
      and be used to supplement general health-related quality of life (HRQoL)
      assessments and pathophysiologic indicators in research and clinical care.
      DESIGN: Cross-sectional data from the Veterans Health Study, an observational
      study of health outcomes in patients receiving Veterans Affairs (VA) ambulatory
      care. SETTING: Four VA outpatient clinics. STUDY SUBJECTS: Two hundred ninety-two
      participants with CLD were identified on the basis of patient report of having a
      physician's diagnosis of chronic bronchitis, emphysema, or asthma and either
      using inhaled medications or having a productive cough on most days for 3 months.
      MEASUREMENTS AND RESULTS: Participants were scheduled for an in-person interview
      in which they completed a CLD questionnaire and measurements of peak expiratory
      flow rate (PEFR). They were also mailed an HRQoL questionnaire, the Short Form
      Health Survey (SF-36). The CLD questionnaire included six symptom items chosen by
      an expert panel (two items each for dyspnea, wheezing, and productive cough). The
      combination of these items yielded a CLD severity index that correlated
      significantly with all eight scales of the SF-36 (range of r, -0.19 to -0.37;
      p<0.01). In contrast, PEFR had statistically significant correlations only with
      two SF-36 scales: physical functioning and bodily pain. CONCLUSIONS: The CLD
      severity index is a reliable and valid patient-administered instrument that may
      be used to evaluate the effects of CLD on general HRQoL and predict future health
      services utilization.

PMID- 9187184
TI  - A safe high-yield technique for cutting needle biopsy of the lung in patients
      with diffuse lung disease.
AB  - The approach to the diagnosis and management of patients with diffuse
      infiltrative lung disease (DILD) is controversial. The results of transbronchial
      biopsy are often unsatisfactory. The role of open lung biopsy is highly variable.
      Percutaneous cutting needle biopsy (CNB) is not recommended because of its
      reported high morbidity/mortality relative to its low diagnostic yield. We report
      a technique for CNB with a high diagnostic yield and a low morbidity and no
      mortality in 228 patients with DILD over the past 23 years. METHODS: The salient
      features of the technique for CNB are as follows: the anesthetic needle does not
      enter the pleural space; a Franklin Silverman needle is inserted into the
      intercostal space posteriorly at outer one-third of chest wall; the biopsy is
      performed with the breath held at normal end expiration; the plane of pleural
      space is broken with sudden insertion of needle 8 to 15 cm into lung; and the
      pathway of the needle is maintained parallel to the lateral chest wall. RESULTS:
      A diagnosis was established in 129 of 145 biopsies (89%) performed by a trained
      operator (A.H.N.). There were 36 pneumothoraces (25%), four minimal hemoptyses
      (3%), and two chest tube placements (1%). There were no deaths (0%). CONCLUSION:
      With meticulous attention to technique and careful selection of patients, the
      procedure offers a relatively safe alternative to open lung or thoracoscopic lung
      biopsy in patients with DILD.

PMID- 9187185
TI  - A comparison of two long-acting vasoselective calcium antagonists in pulmonary
      hypertension secondary to COPD.
AB  - STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and
      may predict mortality in this disorder. We have compared the pulmonary
      vasodilator effects, dose-response characteristics, and tolerability of two
      calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10
      patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH.
      DESIGN: Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg),
      increasing weekly for 3 weeks, in a randomized investigator-blinded crossover
      manner with a 1-week wash-out period between the two treatments. MEASUREMENTS:
      Doppler measurements of pulmonary hemodynamics were made on the seventh day of
      treatment at each drug dose. Lung function, arterial blood gases, and adverse
      events were also monitored weekly. RESULTS: A dose-dependent decline of pulmonary
      artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a
      significant decrease in PAP compared with baseline (20% amlodipine, 17%
      felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that
      were similar for both drugs, but did not reach statistical significance compared
      with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance
      and increase in oxygen delivery with amlodipine and felodipine ER. Lung function
      and blood gas values were stable throughout. Side effects (headache and ankle
      edema) were less frequent during amlodipine treatment (p<0.05). CONCLUSIONS: Both
      amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg,
      are effective pulmonary vasodilators in COPD patients with PH. Their dose
      response characteristics are similar, but amlodipine treatment was associated
      with fewer side effects.

PMID- 9187186
TI  - Human and financial costs of noninvasive mechanical ventilation in patients
      affected by COPD and acute respiratory failure.
AB  - STUDY OBJECTIVES: It has been suggested that noninvasive mechanical ventilation
      (NIMV) may be a time-consuming procedure for medical and paramedical personnel.
      We carried out a prospective trial in 10 consecutive COPD patients aimed at
      assessing the human and economic resources needed to ventilate patients by NIMV
      and we compared these with those needed by a group of six patients receiving
      invasive mechanical ventilation (InMV). DESIGN: The daily cost and the minutes
      spent by medical doctors (MDs), respiratory therapists (RTs), and nurses (Ns)
      were recorded during the first 48 h of ventilation in 10 patients during NIMV
      (group A) and in six who received InMV (group B) after an initial unsuccessful
      attempt with NIMV. In two subgroups of patients (five for group A and four for
      group B), the analysis was also performed, except for RTs, for the total length
      of mechanical ventilation. SETTING: A respiratory ICU. PATIENTS: At hospital
      admission, the two groups of COPD patients did not differ for blood gas values
      (PaCO2 = 88.2+/-9.8 mm Hg for group A vs 90.5+/-12.8 mm Hg for group B, and pH =
      7.21+0.08 vs 7.20+0.08, respectively) or for clinical and neurologic status, but
      patients of group B had not tolerated NIMV. MEASUREMENTS AND RESULTS: The total
      time spent at the bedside in the first 6 h did not differ between group A and B
      (group A = 72.3 min [MD], 87.2 min [RT], and 178.8 min [N] vs 98.8 min [MD], 12.5
      min [RT], and 197.6 min [N] for group B). In the following 42 h, a plateau was
      reached so that there was a significant reduction for both groups in the time of
      assistance given by Ns (p<0.001) but not by MDs or RTs. The total costs were also
      not different between the two groups ($806+/-73 [US dollars per day] vs $864+/-44
      for group A and B, respectively). In the subgroups monitored for the entire
      period of ventilation, a significant reduction in the time of assistance, for
      both MDs and Ns, was observed after approximately the first half. CONCLUSIONS: We
      conclude that in the first 48 h of ventilation, daily NIMV is neither more
      expensive nor time-consuming and staff demanding than InMV. After the first few
      days of ventilation, NIMV was significantly less time-consuming than InMV, for
      MDs and Ns, so that medical and paramedical time expenditure seems not to be a
      major problem during NIMV.

PMID- 9187187
TI  - Comparative physiologic effects of noninvasive assist-control and pressure
      support ventilation in acute hypercapnic respiratory failure.
AB  - STUDY OBJECTIVE: To compare the effects of noninvasive assist-control ventilation
      (ACV) and pressure support ventilation (PSV) by nasal mask on respiratory
      physiologic parameters and comfort in acute hypercapnic respiratory failure
      (AHRF). DESIGN: A prospective randomized study. SETTING: A medical ICU. PATIENTS
      AND INTERVENTIONS: Fifteen patients with COPD and AHRF were consecutively and
      randomly assigned to two noninvasive ventilation (NIV) sequences with ACV and PSV
      mode, spontaneous breathing (SB) via nasal mask being used as control. ACV and
      PSV settings were always subsequently adjusted according to patient's tolerance
      and air leaks. Fraction of inspired oxygen did not change between the sequences.
      MEASUREMENTS AND RESULTS: ACV and PSV mode strongly decreased the inspiratory
      effort in comparison with SB. The total inspiratory work of breathing (WOBinsp)
      expressed as WOBinsp/tidal volume (VT) and WOBinsp/respiratory rate (RR), the
      pressure time product (PTP), and esophageal pressure variations (deltaPes) were
      the most discriminant parameters (p<0.001). ACV most reduced WOBinsp/VT (p<0.05),
      deltaPes (p<0.05), and PTP (0.01) compared with PSV mode. The surface
      diaphragmatic electromyogram activity was also decreased >32% as compared with
      control values (p<0.01), with no difference between the two modes.
      Simultaneously, NIV significantly improved breathing pattern (p<0.01) with no
      difference between ACV and PSV for VT, RR, minute ventilation, and total cycle
      duration. As compared to SB, respiratory acidosis was similarly improved by both
      modes. The respiratory comfort assessed by visual analog scale was less with ACV
      (57.23+/-30.12 mm) than with SB (75.15+/-18.25 mm) (p<0.05) and PSV mode (81.62+/
      25.2 mm) (p<0.01) in our patients. CONCLUSIONS: During NIV for AHRF using
      settings adapted to patient's clinical tolerance and mask air leaks, both ACV and
      PSV mode provide respiratory muscle rest and similarly improve breathing pattern
      and gas exchange. However, these physiologic effects are achieved with a lower
      inspiratory workload but at the expense of a higher respiratory discomfort with
      ACV than with PSV mode.

PMID- 9187188
TI  - Pressure vs flow triggering during pressure support ventilation.
AB  - BACKGROUND: Adult mechanical ventilators have traditionally been pressure- or
      time-triggered. More recently, flow triggering has become available and some
      adult ventilators allow the choice between pressure or flow triggering. Prior
      studies have supported the superiority of flow triggering during continuous
      positive airway pressure, but few have compared pressure and flow triggering
      during pressure support ventilation (PSV). The purpose of this study was to
      compare pressure and flow triggering during PSV in adult mechanically ventilated
      patients. METHODS: The study population consisted of 10 adult patients ventilated
      with a mechanical ventilator (Nellcor-Puritan-Bennett 7200ae) in the PSV mode. In
      random order, we compared pressure triggering of -0.5 H2O, pressure triggering -1
      cm H2O, flow triggering of 5/2 L/min, and flow triggering 10/3 L/min. Pressure
      was measured for 5 min at the proximal endotracheal tube using a data acquisition
      rate of 100 Hz. From the airway pressure signal, trigger pressure (deltaP) was
      defined as the difference between positive end-expiratory pressure (PEEP) and the
      maximum negative deflection prior to onset of the triggered breath. Pressure-time
      product (PTP) was defined as the area produced by the pressure waveform below
      PEEP during onset of the triggered breath. Trigger time (deltaT) was defined as
      the time interval below PEEP during onset of the triggered breath. RESULTS: A
      pressure trigger of -0.5 cm H2O was significantly more sensitive than the other
      trigger methods for deltaP, PTP, and deltaT (p<0.001). There was also a
      significant difference between patients for deltaP, deltaT, and PTP for each
      trigger method (p<0.001). CONCLUSIONS: For this group of patients, flow
      triggering was not superior to pressure triggering at -0.5 cm H2O during PSV.

PMID- 9187189
TI  - Post-ICU mechanical ventilation: treatment of 1,123 patients at a regional
      weaning center.
AB  - STUDY OBJECTIVES: To update our database, reporting changes in the results of
      weaning attempts and profile of patients transferred to us after prolonged
      mechanical ventilation (PMV) in the ICU. DESIGN: Retrospective record review,
      with prospective recording of physiologic measurements on admission from mid
      1994. SETTING: Regional weaning center (RWC). PATIENTS: We studied 1,123
      consecutive ventilator-dependent patients transferred for attempted weaning over
      an 8-year period. MEASUREMENTS AND RESULTS: Median (range) time of mechanical
      ventilation prior to transfer to the RWC declined from 37 (1 to 249) days in 1988
      to 29 (1 to 120) days in 1996 (p<0.05). Acute physiology score of acute
      physiology and chronic health evaluation (APACHE) III was 32 (6 to 123) on RWC
      admission, equaling reported scores soon after ICU admission. Comparing other
      data on admission from 1988 to 1996, mean (+/-SD) serum albumin level declined
      from 2.92+/-0.58 to 2.43+/-0.50 g/dL, and alveolar-arterial oxygen pressure
      difference widened from 106+/-50 to 139+/-99 mm Hg. Prevalence of stage II or
      worse pressure ulceration on admission increased from 34% in 1988 to 46% in 1995.
      Despite these trends, there has been no significant change in patient outcome
      (55.9% weaned, 15.6% failed to wean, 28.8% died) or in median time to wean (29 [1
      to 226] days). Overall survival at 1 year after discharge for the 8-year period
      is 37.9%, improving from 29% in 1988-1991 to 45% since 1992; survival in weaned
      patients discharged to home has improved from 45 to 59% during the respective
      time periods. CONCLUSIONS: Patients are being transferred from the ICU to our RWC
      for attempted weaning sooner in their course of PMV. Although more severely ill
      on arrival than in past years, mortality is unchanged, more than half of the
      patients continue to be successfully weaned, and survival after RWC discharge is
      improved.

PMID- 9187190
TI  - A prospective study of the safety of tracheal extubation using a pediatric airway
      exchange catheter for patients with a known difficult airway.
AB  - STUDY OBJECTIVE: To determine the usefulness of routinely inserting a hollow
      airway exchange catheter (jet stylet) prior to tracheal extubation of adult
      patients with risk factors for difficult tracheal intubation. DESIGN:
      Prospective, 1-year study of 40 consecutive patients undergoing mechanical
      ventilation who had one or more risk factors for difficult tracheal reintubation.
      SETTING: Surgical ICU of a tertiary university medical center. INTERVENTIONS:
      Study patients at risk for difficult tracheal reintubation were extubated using a
      No. 11 Cook airway exchange catheter (CAEC). Following tracheal extubation, the
      CAEC was secured, and humidified oxygen was insufflated through the central lumen
      (2 to 8 L/min) for a minimum of 4 h, during which oxyhemoglobin saturation (SpO2)
      and respiratory frequency were monitored. Stridor or other signs of respiratory
      difficulty were also assessed. The CAEC was removed when it became clinically
      apparent that the need for tracheal reintubation was unlikely. When patients
      failed to respond to tracheal extubation, the CAEC was used to facilitate
      reintubation of these difficult airways. RESULTS: Respiratory distress
      necessitating tracheal reintubation occurred in 3 of 40 patients (8%). One
      patient failed to respond to tracheal extubation twice. None of the patients
      developed oxyhemoglobin desaturation (SpO2 <90%) before or during tracheal
      reintubation. All four reintubations were accomplished during the first attempt
      using the CAEC as a stylet. The CAEC was kept in the trachea for a mean duration
      of 9.4 h. There were no adverse events documented. CONCLUSIONS: The No. 11 CAEC
      is a useful and effective tool for giving patients a trial of extubation.
      Administration of oxygen through the CAEC diminishes the potential for hypoxia
      while maintaining the ability to reintubate the trachea, especially when
      reintubation might prove challenging. Previous data suggest that the CAEC is
      rigid enough to facilitate tracheal reintubation in adults; this was confirmed in
      the three patients in our study who required tracheal reintubation. The risk of
      aspiration, barotrauma, or other airway trauma during prolonged placement of the
      CAEC appears to be low (zero incidence in 40 patients in this study), and use of
      the No. 11 CAEC appeared to be safe. Since oxygen can be delivered through the
      CAEC, it may provide a means to safely evaluate an airway during a trial of
      extubation, ie, a reversible extubation. Finally, oxygen administration through
      the CAEC may obviate the need for facemask or nasal cannula following tracheal
      extubation.

PMID- 9187191
TI  - Assessment of the prognosis of coronary patients: performance and customization
      of generic severity indexes.
AB  - STUDY OBJECTIVE: To assess the prognostic performance of general severity systems
      (APACHE II [acute physiology and chronic health evaluation], simplified acute
      physiology score [SAPS II], and mortality probability models [MPM II]) in
      coronary patients and to derive new customized indexes for coronary patients
      using a reduced number of variables. DESIGN: Inception cohort. SETTING: Adult
      medical and surgical ICUs in 17 hospitals in Catalonia and the Balearic Islands.
      PATIENTS: Four hundred fifty-six patients with acute myocardial infarction.
      MEASUREMENTS AND RESULTS: The APACHE II, SAPS II, and MPM II variables and
      survival status at hospital discharge have been collected. Performance of the
      severity systems was assessed by evaluating calibration and discrimination.
      Logistic regression was used to customize the MPM II(24) and SAPS II indexes.
      Discrimination was high enough for all of the models. However, calibration of the
      MPM II(24) was not as satisfactory as for the other models. The MPM II(24) and
      SAPS II were both reduced to five variables (MPM II(24 cor:) age, PaO2,
      continuous vasoactive drugs, urinary output, and mechanical ventilation; SAPS
      II(cor:) age, PaO2/FI(O2) ratio, systolic BP, Glasgow coma score, and urinary
      output). Both models showed better calibration and discrimination than the
      original ones. CONCLUSIONS: Prognostic indexes developed for multidisciplinary
      patients show good performance when applied to patients with acute myocardial
      infarction, but customization can reduce the number of variables necessary to
      compute them without a loss of, and a possible improvement in, prognostic
      accuracy.

PMID- 9187192
TI  - Noninvasive positive pressure ventilation for acute respiratory failure:
      underutilized or overrated?

PMID- 9187193
TI  - The effects of early chest tube placement on empyema resolution.
AB  - STUDY OBJECTIVES: The objective of this study was to determine the impact of the
      timing of chest tube insertion on outcome for the treatment of empyema, using a
      new animal model of empyema. DESIGN: A prospective, controlled randomized,
      blinded design was used. SETTING: The study was conducted in an animal research
      laboratory. PATIENTS OR PARTICIPANTS: Sixty-six 2- to 3-kg rabbits were used in
      this study. INTERVENTIONS: After induction of empyema, the rabbits were divided
      into four groups. Fourteen rabbits had chest tubes placed at 24 h after empyema
      induction. Seventeen rabbits had chest tubes placed at 48 h and 14 rabbits had
      chest tubes placed at 72 h after empyema induction. Twenty-one rabbits served as
      control rabbits and had no chest tubes placed. MEASUREMENTS AND RESULTS: Ten days
      after induction of empyema, the rabbits were killed. The pleural spaces of each
      rabbit were examined and a gross score, pleural peel score, and a microscopic
      score were calculated for each rabbit. The median gross score, mean pleural peel
      score, and median microscopic scores were significantly higher in the rabbits
      that underwent late chest tube placement (72 h) relative to those that underwent
      early chest tube placement (24 or 48 h). CONCLUSIONS: This study supports
      previous expert opinion statements and conclusions from retrospective analyses
      that early chest tube placement (relative to delayed chest tube placement) is
      beneficial for the treatment of empyema.

PMID- 9187194
TI  - Noninvasive detection of atherosclerotic lesions by 99mTc-based
      immunoscintigraphic targeting of proliferating smooth muscle cells.
AB  - BACKGROUND: Mouse/human chimeric antibody Z2D3 identifies an antigen produced
      exclusively by proliferating smooth muscle cells of human atheroma, and also
      cross reacts with experimentally induced atherosclerotic lesions in rabbits. Fab'
      fragments of Z2D3 antibody were labeled with (99m)Tc using glucaric acid as a
      weak transchelator. The potential role of (99m)Tc-labeled Z2D3 scintigraphy was
      explored for noninvasive imaging of experimental atherosclerotic lesions. METHODS
      AND RESULTS: (99m)Tc-Z2D3 Fab' was utilized for noninvasive imaging in four
      rabbits with experimentally induced atherosclerotic lesions and in one control
      rabbit. In addition, (99m)Tc-labeled nonspecific 103D2 Fab' was used for
      comparison in four other rabbits with atherosclerotic lesions. The
      atherosclerotic lesions were induced by balloon de-endothelialization of the
      infradiaphragmatic abdominal aorta and 12 weeks of hyperlipidemic diet. An
      aliquot of 15 mCi (550 mBq) of (99m)Tc pertechnetate was incubated with 6.25 mg
      of glucaric acid for 30 min followed by incubation of (99m)Tc glucarate with 375
      microg of Z2D3 Fab' or 103D2 Fab' for an additional 30 min. Instant thin-layer
      chromatography demonstrated almost complete radiolabeling. (99m)Tc-Z2D3 was
      administered IV and gamma imaging was performed at the time of injection, 3, 6,
      9, and 12 h, followed by ex vivo imaging of the excised aorta, and
      biodistribution was performed. Unequivocal visualization of atherosclerotic
      lesions was possible in all four animals at 9 to 12 h with Z2D3 Fab'.
      Quantitative uptake, as represented by mean lesion-to-liver count density ratio,
      was 0.6+/-0.05. Imaging with nonspecific 103D2 Fab' did not show any localization
      in the abdominal aorta (lesion-to-liver ratio, 0.45+/-0.02, p=0.02). Ex vivo
      lesion-to-normal aortic segment ratio was 4.3+/-0.9 for Z2D3 and 1.04+/-0.08 for
      nonspecific 103D2 Fab' (p=0.01). Biodistribution studies demonstrated 0.03+/
      0.003% injected Z2D3 dose per gram in the atherosclerotic lesions as compared
      with 0.01+/-0.003% in the nondenuded thoracic aorta of atherosclerotic rabbits
      (p=0.008). However, only 0.008+/-0.002% of the mean injected dose per gram was
      obtained in the atherosclerotic lesions (p=0.001) as compared with 0.005+/-0.003%
      in the normal aortic segments with 103D2. No Z2D3 uptake in normal rabbits was
      observed on either the in vivo or ex vivo images. CONCLUSIONS: The present study
      demonstrates that (99m)Tc-based immunoimaging of the vascular lesions may be
      feasible by the use of smaller antibody fragments. Earlier visualization is
      possible at the expense of a lower absolute antibody uptake in the lesions as
      compared to the use of intact antibody or larger fragments with longer
      circulating time.

PMID- 9187195
TI  - Detection of chromosomal aneuploidy by interphase fluorescence in situ
      hybridization in bronchoscopically gained cells from lung cancer patients.
AB  - BACKGROUND: Development and progression of human malignancies involve multiple
      genetic changes. New techniques to distinguish neoplastic from benign diseases
      unequivocally with small amounts of cells as gained by bronchoscopy are needed to
      come closer to the goal of an early diagnosis in lung cancer. STUDY OBJECTIVE:
      The aim of this study was to determine whether interphase fluorescence in situ
      hybridization (FISH) can be used to visualize chromosomal aberrations in
      bronchoscopically gained cells from lung cancer patients and could eventually
      become a complementary technique to conventional cytology. METHODS: We examined
      20 cancerous specimens (10 primary tumors, 10 malignant effusions) of 18 lung
      cancer patients by FISH with DNA probes specific for chromosomes 3, 8, 11, 12,
      17, and 18. From five additional patients, endobronchial brushings and/or forceps
      biopsy specimens were subjected to interphase FISH analysis. RESULTS: In all
      primary tumors and malignant effusions, highly aneuploid cells were detectable by
      FISH. Chromosomal aberrations always consisted of gains of chromosomal signal
      numbers, and all chromosomes were found to be aneuploid to a similar extent.
      Using chromosomal aneuploidy as a marker of malignancy, material obtained by
      bronchoscopy was then examined for the presence of malignant cells. In all
      specimens, evidence for malignancy was obtained by FISH, including three
      specimens in which cells appeared to be normal or reactively changed by cytologic
      criteria. CONCLUSION: We conclude that interphase FISH is useful in detecting
      aneuploidy associated with malignancy in bronchoscopically gained cells that do
      not clearly meet the criteria of malignancy by conventional cytologic study.

PMID- 9187196
TI  - Gamma-delta T cells in BAL fluid of chronic lower respiratory tract infection.
AB  - Gamma-delta (gamma/delta) T cells are thought to represent the first line of
      defense against various pathogenic microorganisms. The aim of the present study
      was to investigate whether gamma/delta T cells were increased in BAL fluid (BALF)
      of patients with diffuse panbronchiolitis (DPB), a model of chronic lower
      respiratory tract infection. The study population consisted of four groups,
      including patients with DPB, sarcoidosis, idiopathic pulmonary fibrosis, and
      normal subjects. Two-color direct immunofluorescence and flow cytometry were used
      for analysis of peripheral blood or BALF from these patients. The percentage of
      peripheral blood or BALF gamma/delta T cells relative to the total number of
      lymphocytes was similar in the four groups. Although the absolute number of
      gamma/delta T cells in BALF was significantly higher in DPB patients compared
      with the other three groups, the total lymphocyte number in BALF in DPB patients
      was increased and the number of BALF gamma/delta T cells correlated with the
      total lymphocyte number in BALF. Furthermore, the percentage and number of BALF
      gamma/delta T cells were not related to a certain group of pathogenic organisms
      or the number of colony-forming units. Our results suggest that gamma/delta T
      cells are unlikely to play a part in chronic lower respiratory tract infection.

PMID- 9187197
TI  - Managing asymptomatic patients with chronic aortic regurgitation.

PMID- 9187198
TI  - Revisions in the International System for Staging Lung Cancer.
AB  - Revisions in stage grouping of the TNM subsets (T=primary tumor, N=regional lymph
      nodes, M=distant metastasis) in the International System for Staging Lung Cancer
      have been adopted by the American Joint Committee on Cancer and the Union
      Internationale Contre le Cancer. These revisions were made to provide greater
      specificity for identifying patient groups with similar prognoses and treatment
      options with the least disruption of the present classification: T1N0M0, stage
      IA; T2N0M0, stage IB; T1N1M0, stage IIA; T2N1M0 and T3N0M0, stage IIB; and
      T3N1M0, T1N2M0, T2N2M0, T3N2M0, stage IIIA. The TNM subsets in stage IIIB-T4 any
      N M0, any T N3M0, and in stage IV-any T any N M1, remain the same. Analysis of a
      collected database representing all clinical, surgical-pathologic, and follow-up
      information for 5,319 patients treated for primary lung cancer confirmed the
      validity of the TNM and stage grouping classification schema.

PMID- 9187199
TI  - Regional lymph node classification for lung cancer staging.
AB  - Recommendations for classifying regional lymph node stations for lung cancer
      staging have been adopted by the American Joint Committee on Cancer (AJCC) and
      the Union Internationale Contre le Cancer. The objective was to unify the two
      systems that have been in common use for the past 10 years; that is, the schema
      advocated by the AJCC, adapted from the work of Tsuguo Naruke, and the schema
      advocated by the American Thoracic Society and the North American Lung Cancer
      Study Group. Anatomic landmarks for 14 hilar, intrapulmonary, and mediastinal
      lymph node stations are designated. This classification provides for consistent,
      reproducible, lymph node mapping that is compatible with the international
      staging system for lung cancer. It is applicable for clinical and surgical
      pathologic staging.

PMID- 9187200
TI  - Hemoptysis, hepatopulmonary syndrome, and respiratory failure: clinical
      conference on management dilemmas.

PMID- 9187201
TI  - Accelerated lung function decline in swine confinement workers.
AB  - We conducted a longitudinal study to determine the annual rate decline in
      pulmonary function measurements in male swine confinement workers. For
      comparison, a grain farming group and a nonfarming rural-dwelling control group
      were also chosen for the longitudinal study. Two hundred seventeen swine
      confinement workers, 218 grain farmers, and 179 nonfarming control subjects had
      valid pulmonary function measurements at the baseline observation conducted in
      1990 to 1991 and at the second observation conducted in 1994 to 1995. The swine
      confinement workers were younger (mean age=38.3+/-11.7 [SD] years) than the
      nonfarming control subjects (42.6+/-10.4 years) and the grain farmers (44.5+/
      11.9 years). When stratified by age, nonfarming control subjects had the lowest
      mean annual rate decline in FEV1 and FVC in all age categories. The swine
      confinement workers had the largest annual rate decline in FEV1 and FVC, and this
      was most obvious in the middle age categories. After controlling for age, height,
      smoking, and baseline pulmonary function, swine confinement workers had excess
      annual decline of 26.1 mL in FEV1 (p=0.0005), 33.5 mL in FVC (p=0.0002), and 42.0
      mL/s in forced expiratory flow between 25% and 75% of FVC (FEF[25-75%]) (p=0.02)
      over nonfarming control subjects. Grain farmers had excess annual decline of 16.4
      mL in FEV1 (p=0.03), 26.7 mL in FVC (p=0.002), and 11.2 mL/s in FEF(25-75%)
      (p=0.38) over control subjects. These findings suggest that workers engaged in
      the swine industry and grain farmers appear prone to accelerated yearly losses in
      lung function and may therefore be at risk for the future development of chronic
      airflow limitation.

PMID- 9187202
TI  - A consensus approach to diagnosing coronary artery disease based on clinical and
      exercise test data.
AB  - OBJECTIVE: To demonstrate that a consensus approach for combining prediction
      equations based on clinical and exercise test variables derived from different
      populations can stratify patients referred for possible coronary artery disease
      (CAD) into low-, intermediate-, and high-risk groups. DESIGN: Retrospective
      analysis of consecutive patients with complete data from exercise testing and
      coronary angiography referred for evaluation of possible CAD. After derivation of
      a logistic equation in our own training set of patients, this equation, along
      with two other equations developed independently by other investigators, was
      validated in a test set. The validation strategy for the consensus approach
      included the following: (1) calculation of probability scores for each patient
      using each logistic equation independently; (2) determination of probability
      thresholds in the training set to divide the patients into three groups-low risk
      (prevalence CAD <5%), intermediate risk (5 to 70%), and high risk (>70%
      prevalence of CAD); (3) using agreement among at least two of three of the
      prediction equations to generate "consensus" for each patient; and (4)
      application of the consensus approach thresholds to the test set of patients.
      SETTINGS: Two university-affiliated Veteran's Affairs medical centers. PATIENTS:
      We studied 718 consecutive men between 1985 and 1995 who had coronary angiography
      within 3 months of an exercise treadmill test for suspected CAD. The population
      was randomly divided into a training set of 429 patients and a test set of 289
      patients. Patients with previous myocardial infarction or coronary artery bypass
      surgery, valvular heart disease, left bundle branch block, or any Q waves present
      on their resting ECG were excluded from the study. MEASUREMENTS: Recording of
      clinical and exercise test data along with visual interpretation of the ECG
      recordings on standardized forms and abstraction of visually interpreted
      angiographic data from clinical catheterization reports. RESULTS: We demonstrated
      that by using simple clinical and exercise test variables, we could improve on
      the standard use of ECG criteria during exercise testing for diagnosing CAD.
      Using the consensus approach divided the test set into populations with low,
      intermediate, and high risk for CAD. Since the patients in the intermediate group
      would be sent for further testing and would eventually be correctly classified,
      the sensitivity of the consensus approach is 94% and the specificity is 92%. The
      consensus approach controls for varying disease prevalence, missing data,
      inconsistency in variable definition, and varying angiographic criterion for
      stenosis severity. The percent of correct diagnoses increased from the 67% for
      standard exercise ECG analysis and from the 80% for multivariable predictive
      equations alone to >90% correct diagnoses for the consensus approach.
      CONCLUSIONS: The consensus approach has made population-specific logistic
      regression equations portable to other populations. Excellent diagnostic
      characteristics can be obtained using simple data and measurements. The consensus
      approach is best applied utilizing a programmable calculator or a computer
      program to simplify the process of calculating the probability of CAD using the
      three equations.

PMID- 9187203
TI  - Bilateral pleural masses and shortness of breath associated with multiple
      myeloma.

PMID- 9187204
TI  - A 31-year-old man with a thick-walled cyst.

PMID- 9187205
TI  - A woman with cavitating left upper lobe lesion.

PMID- 9187206
TI  - Contamination of hospital compressed air with nitric oxide: unwitting replacement
      therapy.
AB  - BACKGROUND: Inhaled nitric oxide (NO) at levels between 5 and 80 ppm has been
      used experimentally to treat a variety of conditions. NO also is a common
      environmental air pollutant in industrial regions. As compressed hospital air is
      drawn from the local environment, we speculated that it may contain NO
      contamination, which, if present, would provide unwitting inhaled NO therapy to
      all subjects respiring this compressed gas. METHODS: NO levels were measured
      twice daily from ambient hospital air and compressed gas sources driving positive
      pressure ventilation from two adjacent hospitals and compared with NO levels
      reported daily by local Environmental Protection Agency sources. An NO
      chemiluminescence analyzer (Sievers 270B; Boulder, Colo) sensitive to > or =2
      parts per billion was used to measure NO levels in ambient air and compressed
      gas. RESULTS: NO levels in ambient air and hospital compressed air covaried from
      day to day, and absolute levels of NO differed between hospitals with the
      difference never exceeding 1.4 ppm (range, 0 to 1.4 ppm; median, 0.07 ppm). The
      hospital with the highest usage level of compressed air had the highest levels of
      NO, which approximated ambient levels of NO. NO levels were lowest on weekends in
      both hospitals. We also documented inadvertent NO contamination in one hospital
      occurring over 5 days, which corresponded to welding activity near the intake
      port for fresh gas. This contamination resulted in system-wide NO levels of 5 to
      8 ppm. CONCLUSION: Hospital compressed air contains highly variable levels of NO
      that tend to covary with ambient NO levels and to be highest when the rate of
      usage is high enough to preclude natural degradation of NO in 21% oxygen.
      Assuming that inhaled NO may alter gas exchange, pulmonary hemodynamics, and
      outcome from acute lung injury, the role of unwitting variable NO of hospital
      compressed air needs to be evaluated.

PMID- 9187207
TI  - Aortic root dilatation in Marfan's syndrome: a contribution from obstructive
      sleep apnea?
AB  - We report two cases of Marfan's syndrome with coexistent obstructive sleep apnea
      (OSA) in which treatment with nasal continuous positive airway pressure was
      associated with attenuation of aortic root dilatation, a serious complication of
      the syndrome. We speculate that coexistent OSA promotes progressive aortic
      dilatation in some patients with Marfan's syndrome.

PMID- 9187209
TI  - A case of eosinophilic pneumonia and vasculitis induced by diflunisal.
AB  - Drug-induced pneumonitis is an uncommon complication of nonsteroidal anti
      inflammatory drug administration. Herein is the first reported case of
      pneumonitis resulting from diflunisal therapy. The patient demonstrated clinical
      and biopsy evidence of systemic vasculitis. She responded dramatically to
      administration of systemic glucocorticoids.

PMID- 9187208
TI  - A paradoxical effect of bronchodilators.
AB  - Lactic acidosis previously has been reported during treatment of asthma with beta
      2 agonists. However, this metabolic disturbance never had any clinical
      consequence. We report a case of a patient with asthma in whom beta-2 agonist
      administration increased dyspnea by metabolic acidosis due to a sharp increase in
      lactate levels (hyperlactatemia) and led to inappropriate intensification of
      bronchodilator therapy.

PMID- 9187210
TI  - Subglottic stenosis complicating cardiac surgery in children.
AB  - OBJECTIVE: To highlight the incidence of subglottic stenosis (SGS) as a
      complication of surgery for congenital heart disease and the role of single-stage
      laryngotracheoplasty in treating this complication. DESIGN: Retrospective case
      series. SETTING: University-based referral center specializing in surgery for
      congenital heart disease and complex airway problem management. INTERVENTION:
      Laryngotracheal reconstruction (LTR). MAIN OUTCOME MEASURE: Successful airway
      expansion. RESULTS: At last follow-up, 87.5% (7 of 8) of patients remain free of
      obstructive airway symptoms. CONCLUSION: SGS can complicate surgery for
      congenital heart disease in children. Single-stage LTR is an effective treatment
      modality for this problem.

PMID- 9187211
TI  - Management of a giant fluid-filled bulla by closed-chest thoracostomy tube
      drainage.
AB  - A 53-year-old man was admitted to the hospital for management of pneumonia and a
      giant fluid-filled bulla. He appeared acutely ill and had persistent fever
      despite prolonged therapy with parenteral antibiotics and aggressive bronchial
      drainage. Percutaneous placement of an 8.5F catheter into the bulla enabled
      drainage of both fluid and air within the bulla and led to resolution of his
      symptoms within 24 h. This report demonstrates that drainage of giant fluid
      filled bullae may lead to rapid resolution of symptoms and describes a novel
      management technique for this condition.

PMID- 9187212
TI  - Hemoptysis as the presenting symptom in bronchiolitis obliterans organizing
      pneumonia.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon but
      increasingly recognized pulmonary entity that usually presents with symptoms of
      dyspnea, cough, and fever. The medical literature describes rare cases of
      hemoptysis in BOOP, with very small quantities of blood expectorated. We describe
      two cases of BOOP, one idiopathic and one in association with rheumatoid
      arthritis, in which large-quantity hemoptysis was the primary presenting symptom.

PMID- 9187213
TI  - Movement disorders associated with withdrawal from high-dose intravenous
      haloperidol therapy in delirious ICU patients.
AB  - Intravenous haloperidol is recommended as the drug of choice to treat delirium in
      ICU patients. Movement disorders and other adverse events commonly occur with
      oral haloperidol use but are rarely seen with IV haloperidol use, and withdrawal
      symptoms have not been reported with short-term ICU use. We describe self-limited
      dyskinesia during withdrawal of high-dose continuous IV haloperidol therapy in
      five ICU patients.

PMID- 9187214
TI  - Acute lupus pneumonitis with normal chest radiograph.
AB  - Patients with acute lupus pneumonitis (ALP) usually have hypoxemia, patchy
      infiltrates evidenced on a chest x-ray film, and an incomplete response to
      corticosteroids with high mortality. In contrast, lupus patients with a syndrome
      of acute reversible hypoxemia (SARH) have hypoxemia with normal chest x-ray films
      and a rapid response to corticosteroids. We present a case of biopsy-proven ALP
      with normal initial chest x-ray films, and a normal CT scan. We hypothesize that
      a continuum of vascular and parenchymal abnormalities may exist in the lungs of
      lupus patients. This case also illustrates the insensitivity of routine chest
      radiographs in demonstrating mild or early pneumonitis.

PMID- 9187215
TI  - Pulmonary vasculopathy and recurrent pneumothoraces.

PMID- 9187216
TI  - Therapeutic thoracoscopy under local anesthesia.

PMID- 9187217
TI  - Is measurement of cardiac output using impedance cardiography accurate?

PMID- 9187218
TI  - Air, by any other name...

PMID- 9187219
TI  - An alternative to the football helmet.

PMID- 9187220
TI  - Hepatic bleeding and hemorrhagic shock following thrombolytic therapy in patients
      with acute myocardial infarction.

PMID- 9187221
TI  - Cardiopulmonary effects of laparoscopic surgery, revisited.

PMID- 9187222
TI  - Antibiotics in acute bronchitis and exacerbations of chronic bronchitis: what is
      general practitioners' habit?

PMID- 9187223
TI  - Towards better pertussis vaccines.
AB  - Several recently completed trials have shown that acellular pertussis vaccines
      induce substantial protection against pertussis. They are considerably less
      reactogenic than whole-cell vaccines and, as they consist of only one or a few
      purified proteins, they can be expected to cause less severe adverse events. The
      optimal composition of acellular vaccines has not yet been determined. The number
      of vaccine antigens varies from one to five. All vaccines contain detoxified
      pertussis toxin. Other antigens included in several vaccines are filamentous
      haemagglutinin, pertactin and fimbriae, but it remains to be proven that these
      antigens contribute significantly to protection. Postlicensure studies will be of
      importance in order to study possible rare adverse events after acellular
      vaccines and to study the induction of herd immunity.

PMID- 9187224
TI  - Do we need adjuvant treatment for rectal cancer?
AB  - Recent studies have shown improved local control of rectal cancer in patients
      receiving preoperative radiotherapy. The reduction of local recurrence is about
      50% both after 25 Gy in 5 days and 40 Gy over 4 weeks. Furthermore an improvement
      in survival of about 20% has been found. The long-term side-effects are still not
      fully evaluated. Adjuvant chemotherapy studies in Dukes' C patients have shown a
      significant increase in survival of between 22 and 39%. An initial study using 17
      1A antibodies also in Dukes' C patients has shown a 30% increase in survival
      rate. However, a drawback of the trials that tested adjuvant treatment 5 to 10
      years ago is that they do not reflect the modern surgical technique using
      perimesorectal clearance and total mesorectal excision. Centres not using
      adjuvant therapy are now reporting local recurrence rates of 5-10%, which is
      superior to surgery plus adjuvant therapy in all previously published trials. It
      is therefore urgent to study the effects of preoperative irradiation in patients
      operated on with the current surgical technique and carefully balance the side
      effects against the benefits. The aim must be to obtain knowledge of how to
      select a subgroup of patients who definitely needs preoperative radiotherapy,
      e.g. those undergoing an abdominoperineal excision. Systemic adjuvant therapy is
      probably increasing survival rate in Dukes' C patients but more studies are
      necessary, particularly with the 17-1A antibody.

PMID- 9187225
TI  - Phyto-oestrogens and Western diseases.
AB  - Incidences of breast, colorectal and prostate cancer are high in the Western
      world compared to countries in Asia. We have postulated that the Western diet
      compared to the semivegetarian diet in some Asian countries may alter hormone
      production, metabolism or action at the cellular level by some biochemical
      mechanisms. Our interest has been focused on two groups of hormone-like
      diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids
      abundant in plasma of subjects living in areas with low cancer incidence. The
      precursors of the biologically active compounds detected in man are found in
      soybean products, whole-grain cereal food, seeds, and berries. The plant lignan
      and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like
      compounds. The weakly oestrogenic diphenols formed influence sex-hormone
      production, metabolism and biological activity, intracellular enzymes, protein
      synthesis, growth factor action, malignant cell proliferation, differentiation,
      cell adhesion and angiogenesis in such a way as to make them strong candidates
      for a role as natural cancer-protective compounds. Their effect on some of the
      most important steroid biosynthetic enzymes may result in beneficial modulation
      of hormone concentrations and action in the cells preventing development of
      cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal
      dryness in postmenopausal women and may to some degree inhibit osteoporosis, but
      alone they may be insufficient for complete protection. Soy intake prevents
      oxidation of the low-density lipoproteins in vitro when isolated from soy-treated
      individuals and affect favourably plasma lipid concentrations. Animal experiments
      provide evidence suggesting that both lignans and isoflavonoids may prevent the
      development of cancer as well as atherosclerosis. However, in some of these
      experiments it has not been possible to separate the phyto-oestrogen effect from
      the effect of other components in the food. The isoflavonoids and lignans may
      play a significant inhibitory role in cancer development particularly in the
      promotional phase of the disease, but recent evidence points also to a role in
      the initiation stage of carcinogenesis. At present, however, no definite
      recommendations can be made as to the dietary amounts needed for prevention of
      disease. This review deals with all the above-mentioned aspects of phyto
      oestrogens.

PMID- 9187226
TI  - The role of apoptosis in gynaecological malignancies.
AB  - Apoptosis is a process of single-cell deletion requiring active participation of
      the cell in its own demise. First described in 1972, it is now known to play a
      major role in embryogenesis, tissue homeostasis and neoplasia. Apoptosis can be
      initiated when DNA damage occurs causing the cell to pause in its reproductive
      cycle. If the DNA damage is beyond repair, the cell proceeds to apoptotic cell
      death. When the genetic mechanism(s) involved in the pathway of apoptosis is
      altered, the cell does not die. Further mutations occur by proliferation and such
      multiple mutational events can lead to a malignant phenotype and cancer growth.
      The tumour suppressor gene p53 causes a DNA-damaged cell to rest and attempt
      repair. If damage is irreparable, p53 levels will continue to increase,
      initiating apoptosis. Mutation of p53, found in approximately 50% of cancers, can
      stop the apoptotic process. Increased bcl-2 expression, an apoptosis inhibitor,
      also plays a role in cellular transformation and cancer growth. Its altered
      expression occurs in the presence of oncogene expression. This paper reviews the
      role of apoptosis in malignant transformation, cancer growth, and response to
      therapy for gynaecological cancers. For cervical cancer and its precursors, data
      on apoptotic index, bcl-2 and Bax expression are presented and discussed in
      relationship to human papillomavirus expression. In ovarian epithelial
      malignancies, the role that apoptosis plays in chemotherapeutic responses is
      reviewed. The data for endometrial cancer are currently limited to apoptotic
      index.

PMID- 9187227
TI  - Total mesorectal excision--the new golden standard of surgery for rectal cancer.
AB  - Rectal cancer persists as a significant worldwide problem. Currently, surgery is
      associated with a poor prognosis, a high likelihood of permanent colostomy and a
      high rate of local recurrence in patients with regional disease (transmural
      penetration or involvement of regional mesenteric lymph nodes). Functional
      changes such as impotence and bladder dysfunction remain distressingly common
      consequences of conventional surgery. Over the past two decades, a fundamental
      change in operative technique has taken place. Conventional surgery (which is
      performed using blunt technique along undefinable tissue planes) has given way to
      sharp dissection along definable planes. The technique known as total mesorectal
      excision (TME) or complete circumferential mesorectal excision (CCME) produces
      the complete resection of an intact package of the rectum and its surrounding
      mesorectum, enveloped within the visceral pelvic fasia with uninvolved
      circumferential margins. As a result of TME, 5-year survival figures have risen
      from 45-50% to 75%, local recurrence rates have declined from 30% to 5-8%,
      sphincter preservation has risen by at least 20% for mid- and lower rectal
      cancers, and the rates of impotence and bladder dysfunction have declined from 50
      85% to 15% or less. Patients with rectal cancer can now have a good prognosis,
      and intact image and high quality of life. The integration of multidisciplinary
      radiation therapy and chemotherapy into the care of patients undergoing TME or
      CCME for rectal cancer is presently under clinical trial.

PMID- 9187228
TI  - The relation of chronic diseases to all-cause mortality risk--the Seven Countries
      Study.
AB  - The relation of chronic conditions on all-cause mortality in population samples
      was studied based on observations from the Seven Countries Study. The objective
      of this work was to study the risk of death during a 15-year follow-up of middle
      aged men in relation to six chronic diseases. Fifteen cohorts of men aged 50-69,
      totalling 8122 subjects, were examined around 1970 in seven countries: Finland,
      The Netherlands, Italy, Croatia (former Yugoslavia), Serbia (former Yugoslavia),
      Greece and Japan. Clinical diagnoses findings were made for coronary heart
      disease (CHD), 'other heart diseases' (OTH), peripheral arterial disease (PAD),
      stroke (STR), chronic obstructive pulmonary disease (COPD), and diabetes mellitus
      (DIAB). All-cause mortality was assessed in the subsequent 15 years. Death rates
      and relative risks were estimated from crude data, and in proportional hazards
      models after adjustment for age, systolic blood pressure and serum cholesterol
      level, cigarette smoking and body mass index. Large regional differences were
      found in the prevalence of the six conditions. Weak relations were found between
      population prevalence of each disease and population death rates for that
      disease. Among cohorts the relative risk of death in 15 years from any cause,
      adjusted for other risk factors, showed little variation among countries. Pooled
      relative risks, adjusted by the inverse of variance (with 95% CI) were: for CHD,
      1.81 (1.60-2.06); for OTH, 1.47 (1.28-1.69); for PAD, 1.64 (1.39-1.93); for STR,
      1.56 (1.23-1.98); for COPD, 1.67 (1.48-1.88); and for DIAB, 1.75 (1.43-2.15). The
      smallest variability of prognosis among countries was found for CHD, OTH and
      DIAB; the largest for PAD, STR and COPD. Despite simple clinical diagnostic
      procedures and large differences in prevalence, the relation of established
      prevalent conditions to subsequent all-cause mortality is relatively uniform
      among countries and across these conditions, with a relative risk of dying in 15
      years usually ranging between 1.5 and 2.0.

PMID- 9187229
TI  - Paediatric rheumatology today.
AB  - A brief survey of paediatric rheumatology as a subspecialty is given, stressing
      the need of training programmes in paediatric rheumatology in the European
      countries.

PMID- 9187230
TI  - The cytokine network in juvenile chronic arthritis.
AB  - This is a brief overview of the cytokine network within juvenile chronic
      arthritis, introducing the concept of the production of T-helper 1 (TH-1) or TH2
      cell differentiation as a result of cytokine production, as well as the concept
      of the balance between pro- and anti-inflammatory cytokines. The balance of TH1
      and TH2 cells of pro- and anti-inflammatory cytokines could be altered as a
      result of genetic differences in the expression levels of a number of key
      cytokines and may be the critical events leading to chronic inflammation.
      Finally, the importance of identifying molecular targets for intervention therapy
      to change the balance of the cytokine network is proposed.

PMID- 9187231
TI  - Viruses and childhood arthritis.
AB  - The role of viral infections in the aetiology of acute and chronic arthritides of
      childhood is incompletely understood. The fact that some viruses cause acute
      arthritis is certain, although in most instances of presumed viral arthritis no
      agent is identified. The associations of viruses with diseases such as juvenile
      chronic arthritis (JCA) are limited, and have been difficult to prove with
      certainty. Rubella, parvovirus B19 and influenza AH2N2 have been shown by
      culture, serology or epidemiology to be related to at least some cases of JCA in
      some studies, but not in others. A rationale for pursuing investigations of viral
      aetiology of chronic arthritis is discussed, and a strategy involving early
      disease detection and close collaboration between clinicians and scientists is
      proposed.

PMID- 9187233
TI  - The clinical significance of antiphospholipid antibodies.
AB  - The antiphospholipid syndrome is defined as the association between the presence
      of antiphospholipid antibodies, detected as anticardiolipin antibodies and/or
      lupus anticoagulant, and a history of either arterial or venous thrombosis and/or
      recurrent pregnancy loss. Because thrombosis may occur in virtually any organ
      system, diagnosing the antiphospholipid syndrome and taking appropriate
      anticoagulation measures are important considerations in all medical specialties.
      Antiphospholipid antibody-associated thrombosis tends to recur. Antithrombotic
      prophylaxis to prevent recurrences is therefore needed. Prophylaxis in
      individuals with circulating antiphospholipid antibodies who have no history of
      thrombosis is still controversial. Although direct evidence for a pathogenetic
      role of antiphospholipid antibodies in the development of thrombosis is still
      lacking, recent studies suggest that it is causative rather than coincidental.
      New insights on the possible mechanisms leading to thrombosis were provided by
      the discovery of the serum cofactor (beta2-GPI), a coagulation inhibitor which is
      required for binding of anticardiolipin antibodies to cardiolipin. More recently,
      patients with antiphospholipid antibodies were found to possess autoantibodies
      directed against other coagulation factors, including prothrombin, protein C and
      protein S. Future studies should clarify whether these different antigenic
      specificities are associated with particular clinical events and assess the risk
      of thrombosis associated with the presence of antiphospholipid antibodies in
      asymptomatic individuals.

PMID- 9187232
TI  - Host-microbe interaction in HLA-B27-associated diseases.
AB  - The mechanisms leading to the development of HLA-B27-associated diseases,
      spondyloarthropathies, are unknown. One of them, reactive arthritis, is clearly
      caused by an infection, and joint inflammation develops soon after or during an
      infection elsewhere in the body. In other forms of spondyloarthropathies, such as
      ankylosing spondylitis, association with infection is suggested but it is not as
      clear. Pathogenetic mechanisms of reactive arthritis are a focus of great
      interest as causative infections and strong genetic association are known. How
      HLA-B27 determines the appearance of joint complications after certain infections
      is not clear. Several theories have been proposed to explain the association, and
      they usually include the idea that interaction between microbe and host is
      abnormal and inefficient in HLA-B27-positive subjects in whom reactive arthritis
      develops.

PMID- 9187234
TI  - International trials in paediatric rheumatology: current status.
AB  - Current treatment of children with juvenile chronic arthritis (JCA) has been
      changed significantly by the results of randomized controlled trials (RCTs).
      However, due to low market appeal of JCA, few RCTs are being funded by drug
      companies and none in the more rare childhood rheumatic diseases. In addition,
      RCTs have several limitations when used for a chronic illness such as JCA. To
      deal with this situation, the Pediatric Rheumatology International Trials
      Organization (PRINTO) is being organized to perform effectiveness trials in
      addition to efficacy trials in a variety of paediatric rheumatic illnesses.

PMID- 9187235
TI  - Combination of second-line antirheumatic drugs.
AB  - Single drug therapy is often not satisfactory in the treatment of chronic
      arthritis. The combination of second-line antirheumatic drugs is therefore
      increasingly employed. Various strategies of combining drugs can be used,
      starting with combinations or adding agents in case of insufficient effect of
      single therapy. Effective combinations have to be found empirically because lack
      of knowledge about pharmacodynamics and pharmacokinetics often hinders rational
      choices. Few controlled studies on combinations of second-line antirheumatic
      drugs exist, results suggesting very moderately increased efficacy and increased
      toxicity. Recently, results of combinations, mainly with methotrexate, have
      become available. Combining this agent with azathioprine did not offer
      advantages. Cyclosporin added to insufficiently effective methotrexate possibly
      has some value and antimalarials combined with methotrexate may be beneficial
      regarding effectivity and/or toxicity. Methotrexate added to insufficiently
      effective sulphasalazine seems to be better than methotrexate alone, although
      this combination when used from the start of the therapy was disappointing.
      Triple therapy of the latter combination together with hydroxychloroquine turned
      out to be superior to single methotrexate and to the combination of
      sulphasalazine and hydroxychloroquine. Surprisingly, the toxicity of these
      combinations was mainly comparable to single therapy. In conclusion, combinations
      of second-line antirheumatic drugs have a role, although not yet clearly defined,
      in the therapy of chronic arthritis.

PMID- 9187236
TI  - Rare vasculitic syndromes.
AB  - Vasculitis can and does occur in childhood. Apart from the common vasculitides
      (Henoch-Schonlein purpura, hypersensitivity angiitis and Kawasaki disease) there
      are a number of important but comparatively rare disorders affecting children.
      These include macroscopic and microscopic polyarteritis, cutaneous polyarteritis,
      Wegener's granulomatosis, Churg-Strauss syndrome, primary angiitis of the central
      nervous system, hypocomplimentaemic urticarial vasculitis, vasculitis associated
      with various connective tissue disorders, Takayasu's disease and vasculitis
      associated with conditions such as Behcet's syndrome, familial Mediterranean
      fever and Cogan's syndrome. Distinguishing these conditions from other disorders
      is often difficult and requires clinical acumen and appropriate investigative
      procedures. With modern therapeutic agents it is possible to implement
      appropriate therapy but in spite of this, there remains a not inconsequential
      morbidity and mortality.

PMID- 9187237
TI  - Cloning and characterization of a protein phosphatase type 1-binding subunit from
      smooth muscle similar to the glycogen-binding subunit of liver.
AB  - A yeast two-hybrid screen of a chicken gizzard cDNA library detected the
      interaction of the catalytic subunit of protein phosphatase type 1 with a novel
      subunit. Subsequent characterization established similarity (58%) to the rat
      liver glycogen-binding subunit. Northern analyses showed expression in a wide
      range of tissues.

PMID- 9187238
TI  - Characterization and mutational studies of equine infectious anemia virus
      dUTPase.
AB  - The macrophage tropic lentivirus, equine infectious anemia virus (EIAV), encodes
      a dUTPase in the pol gene that is required for efficient replication in
      macrophages. Two naturally occurring variants of the enzyme were expressed as
      recombinant proteins in Escherichia coli; metal chelate affinity chromatography
      was used to purify histidine-tagged recombinant enzymes to greater than 80%
      homogeneity in a single chromatographic step. Biochemical and enzymatic analyses
      of these preparations suggest that this method yields dUTPase that is suitable
      for detailed mutational analysis. Specific activities of preparations ranged from
      4 x 10(3) to 5 x 10(4) units/mg. Recombinant EIAV dUTPase was highly specific for
      dUTP with a Km in the range of 3 to 8 microM. The enzyme was sensitive to
      inhibition by dUDP with little inhibition by other nucleotides or the reaction
      products, dUMP and PPi. The subunit organization of recombinant EIAV dUTPase was
      probed by gel filtration, glycerol gradient centrifugation, and chemical cross
      linking, and is a trimer. We have begun mutational analyses by targeting a
      conserved domain present at the carboxyl terminus of all dUTPases that shares
      high homology to the phosphate binding loops (P-loops) of a number of ATP- and
      GTP-binding phosphatases. The P-loop-like motif of dUTPases is glycine rich but
      lacks the invariant lysine found in authentic P-loops. Deletion of this motif
      leads to loss of dUTPase activity; a series of point mutations that have been
      shown to inactivate authentic P-loops also abolish EIAV dUTPase activity.

PMID- 9187239
TI  - Characterization of the affinity of the G(M2) activator protein for glycolipids
      by a fluorescence dequenching assay.
AB  - The G(M2) activator protein is a substrate specific cofactor for degradation of
      G(M2) ganglioside by lysosomal beta-hexosaminidase A. Mutations in the gene
      encoding the activator result in the AB-variant form of G(M2) gangliosidosis. The
      activator protein contains at least three functional elements; a hydrophobic
      binding pocket, an oligosaccharide binding site(s), and an area that interacts
      with hexosaminidase A. In this report a fluorescence dequenching assay specific
      for only the hydrophobic binding pocket is evaluated and optimized. It is shown
      that various glycolipids inhibit the transport between liposomes of a self
      quenching fluorescent lipid probe, octadecylrhodamine, by the activator protein.
      The level of inhibition produced by each glycolipid is then used to characterize
      the oligosaccharide-binding specificity of the activator. The fluorescence
      dequenching assay is also used to evaluate the functionality of a truncated form
      of the activator protein. Our results indicate that this simple assay can be used
      to determine structure-function relationships within the normal or mutant forms
      of the activator. The data suggest that the C-terminus of the activator is
      required to produce a functional hydrophobic binding pocket.

PMID- 9187240
TI  - Identification of beta2-glycoprotein I as a membrane-associated protein in
      kidney: purification by calmodulin affinity chromatography.
AB  - Outer renal medulla calmodulin-binding proteins from a soluble protein fraction
      and a plasma membrane fraction solubilized in CHAPS were retained on a calmodulin
      Sepharose 4B column in the presence of Ca2+, and subsequently eluted by EGTA. The
      calmodulin-binding proteins constituted 2.5% of the soluble protein and 0.1% of
      the solubilized membrane protein. beta2-glycoprotein I was identified as a
      calmodulin-binding protein both by N-terminal sequencing and by immunoblotting.
      Quantification showed that beta2-glycoprotein I constituted the major part
      (approx. 35%) of the calmodulin-binding membrane proteins, but only a minor part
      (approx. 0.1%) of the calmodulin-binding proteins in the soluble fraction. These
      results show for the first time that beta2-glycoprotein I binds calmodulin and
      that beta2-glycoprotein I may in kidney be a membrane-associated protein.
      Immunohistochemical studies identified beta2-glycoprotein I in several parts of
      the cortex and the medulla of the kidney, including Bowman's capsula, the tubular
      lumen and the tubular epithelium, indicating that beta2-glycoprotein I, despite
      its relatively high molecular mass, is filtrated in the glomerulus and
      subsequently reabsorbed by the tubular epithelium. This is in agreement with
      beta2-glycoprotein I being a marker for renal tubular disease.

PMID- 9187241
TI  - Characterization of the interaction between beta2-glycoprotein I and calmodulin,
      and identification of a binding sequence in beta2-glycoprotein I.
AB  - beta2-Glycoprotein I was shown to bind reversibly to calmodulin in a Ca2+
      dependent manner with a 1:1 stoichiometry, a Kd of 3 x 10(-9) M and a Hill
      coefficient of 1.4. A sequence in beta2-glycoprotein I (Lys-Pro-Gly-Tyr-Val-Ser
      Arg-Gly-Gly-Met-Arg-Lys-Phe-Ile-) limited by Cys-32 and Cys-47 is suggested to be
      the calmodulin-binding region. This sequence was the only one in beta2
      glycoprotein I theoretically having the ability to form a basic amphiphilic alpha
      helix typical of a calmodulin binding sequence. The peptide corresponding to this
      sequence was synthesized and found to inhibit the interaction between beta2
      glycoprotein I and calmodulin with an IC50 value of 0.38 x [beta2-glycoprotein I]
      and to displace the beta2-glycoprotein I from the beta2-glycoprotein I/calmodulin
      complex with an IC50 value of 0.90 x [beta2-glycoprotein I].

PMID- 9187242
TI  - Site-specific modification of rabbit muscle creatine kinase with sulfhydryl
      specific fluorescence probe by use of hydrostatic pressure.
AB  - We investigated the effect of pressure on the reactivity of cysteine residues of
      rabbit muscle creatine kinase (CK). Performing the fluorescent modification under
      high pressure, a unique sulfhydryl group (Cys-253) of CK was labeled, in addition
      to Cys-282, which is known as a single reactive sulfhydryl under ambient
      conditions. CK is composed of two identical subunits, containing four cysteine
      residues in each subunit. Cys-282 plays an important role in enzymatic activity.
      In the pressure range from 0.1 MPa to 300 MPa, only one sulfhydryl group for each
      subunit of CK reacted with the reagents. However, at 400 MPa 2 sulfhydryl groups
      were modified. The 2-nitro-5-thiocyanobenzoic acid (NTCB) cleavage method
      revealed that both Cys-282 and Cys-253 were modified at 400 MPa. The chemical
      modification of Cys-282 induced a loss of enzymatic activity. By taking advantage
      of the modification under high pressure, selective modification of Cys-253 with 5
      [N-(iodoacetamidoethyl)amino]-naphthalene-1-sulfonate (IAEDANS) was performed. A
      reversible blocking of Cys-282 at atmospheric pressure was followed by the
      reaction of Cys-253 with the fluorescent probe at 400 MPa. After the
      decompression, Cys-282 was unblocked, and obtained Cys-253-modified CK retained
      up to 64% of the catalytic activity of the intact CK. The fluorescent properties
      of IAEDANS covalently bound at Cys-253 were not significantly different from
      those of IAEDANS covalently bound at Cys-282.

PMID- 9187243
TI  - Target size analysis of an avermectin binding site from Drosophila melanogaster.
AB  - A high-affinity avermectin binding site from Drosophila melanogaster head
      membranes was subjected to target size analysis by radiation inactivation in
      order to determine the functional unit size. Using the [3H]ivermectin binding
      assay to assess ligand binding activity, the target size was determined to be
      44.3 +/- 3.9 kDa. This result suggests that the size of the functional unit
      required for high-affinity ligand binding is a monomer. The membrane-associated
      acetylcholinesterase present in the Drosophila head membranes was also analyzed
      by radiation inactivation and served as a control. By monitoring enzymatic
      activity, the functional unit size of the Drosophila acetylcholinesterase was
      determined to be 70 +/- 9.7 kDa. This corresponds to the molecular weight of a
      dimer composed of a 55 kDa subunit and a 16-18 kDa subunit.

PMID- 9187244
TI  - Glutathione alters the mode of calcium-mediated regulation of adenylyl cyclase in
      membranes from mouse brain.
AB  - We examined the effect of sulfhydryl compounds on the regulation of adenylyl
      cyclase by calcium in mouse cerebrum membranes. Isoproterenol-stimulated adenylyl
      cyclase (IP-AC) activity in the membranes was increased by addition of the
      optimum concentrations of calcium/calmodulin. However, in the presence of 0.01
      0.07 mM glutathione (GSH), calcium/calmodulin inhibited the activity. At high
      concentrations of GSH (1-10 mM), the IP-AC activity was stimulated by
      calcium/calmodulin to a greater extent than that in the control (no GSH).
      Cysteine at less than 1.7 mM induced a similar inhibition of the IP-AC activity,
      but dithiothreitol did not. The activity of IP-AC measured in the absence of
      calmodulin decreased when calcium levels were greater than 300 microM. GSH at
      0.05 mM enhanced the calcium-dependent inhibition (22% inhibition by 200 microM
      calcium), while 10 mM GSH lowered it. Calmodulin itself had no significant effect
      on the IP-AC activity, irrespective of the concentrations of GSH involved. It
      caused a small increase in the IP-AC activity that had been reduced by the
      presence of calcium and GSH. These results indicate that the redox status of
      sulfhydryls in adenylyl cyclase plays an important role in the calcium-mediated
      regulation of the enzyme. The enzyme becomes much more sensitive to the calcium
      dependent inhibition after partial reduction of the sulfhydryls via the
      particular mode of reactin.

PMID- 9187245
TI  - Structure of membrane glutamate carboxypeptidase.
AB  - Membrane glutamate carboxypeptidase (mGCP) hydrolyses pteroylpoly-gamma
      glutamates, methotrexate tri-gamma-glutamate and N-acetyl-aspartyl-alpha
      glutamate. The enzyme is thought to be required for intestinal uptake of folate,
      for the resistance of some tumours to methotrexate, and for the metabolism of N
      acetyl-aspartyl-glutamate, an abundant neuropeptide. It has recently been
      reported that mGCP is a protein also known as prostate-specific membrane antigen,
      homologous with transferrin receptor. This allows us to predict the domain
      structure of mGCP. Moreover, we have been able to assign the catalytic domain of
      mGCP to peptidase family M28, which contains cocatalytic zinc metallopeptidases.
      On the basis of the known structure of an aminopeptidase in family M28, we
      predict that Asp377, Asp387, Glu425, Asp453 and His553 are ligands of two atoms
      of zinc bound in the catalytic site of mGCP, and suggest that the aminopeptidases
      of Vibrio and Streptomyces can serve as valuable models in the design of
      inhibitors for this medically important enzyme.

PMID- 9187246
TI  - Acetylcholinesterases from Elapidae snake venoms: biochemical, immunological and
      enzymatic characterization.
AB  - We analyzed 45 batches of venom from 20 different species belonging to 11 genera
      from the 3 main families of venomous snakes (Elapidae, Viperidae and Crotalidae).
      We found high acetylcholinesterase (AChE) activity in all venoms from Elapidae,
      except in those from the Dendroaspis genus. AChE was particularly abundant in
      Bungarus venoms which contain up to 8 mg of enzyme per gram of dried venom. We
      could not detect acetylcholinesterase activity in any batch of venom from
      Viperidae or Crotalidae. Titration of active sites with an organophosphorous
      agent (MPT) revealed that the AChE of all venoms have similar turnovers (6000 to
      8000 s(-1)) which are clearly higher than those of Torpedo and mammalian enzymes
      but lower than that of Electrophorus. AChEs from the venom of elapid snakes of
      the Bungarus, Naja, Ophiophagus and Haemacatus genera were purified by affinity
      chromatography. SDS-PAGE analysis and sucrose gradient centrifugation
      demonstrated that AChE is exclusively present as a nonamphiphilic monomer. These
      enzymes are true AChEs, hydrolyzing acetylthiocholine faster than
      propionylthiocholine and butyrylthiocholine and exhibiting excess substrate
      inhibition. Twenty-seven different monoclonal antibodies directed against AChE
      from Bungarus fasciatus venom were raised in mice. Half of them recognized
      exclusively the Bungarus enzyme while the others cross-reacted with AChEs from
      other venoms. Polyspecific mAbs were used to demonstrate that venoms from
      Dendroaspis, which contain the AChE inhibitor fasciculin but lack AChE activity,
      were also devoid of immunoreactive AChE protein. AChE inhibitors acting at the
      active site (edrophonium, tacrine) and at the peripheral site (propidium,
      fasciculin), as well as bis-quaternary ligands (BW284C51, decamethonium), were
      tested against the venom AChEs from 11 different species. All enzymes had a very
      similar pattern of reactivity with regard to the different inhibitors, with the
      exception of fasciculin. AChEs from Naja and Haemacatus venoms were relatively
      insensitive to fasciculin inhibition (IC50 >> 10(-6) M), while Bungarus (IC50
      approximately 10(-8) M) and especially Ophiophagus (IC50 < 10(-10) M) AChEs were
      inhibited very efficiently. Ophiophagus and Bungarus AChEs were also efficiently
      inhibited by a monoclonal antibody (Elec-410) previously described as a specific
      ligand for the Electrophorus electricus peripheral site. Taken together, these
      results show that the venoms of most Elapidae snakes contain large amounts of a
      highly active non-amphiphilic monomeric AChE. All snake venom AChEs show strong
      immunological similarities and possess very similar enzymatic properties.
      However, they present quite different sensitivity to peripheral site inhibitors,
      fasciculin and the monoclonal antibody Elec-410.

PMID- 9187247
TI  - Purification and characterization of two new cytochrome P-450 related to CYP2C
      subfamily from rabbit small intestine microsomes.
AB  - Two forms of cytochrome P-450, designated P-450id and P-450ie, were purified to
      specific contents of 14.3 and 15.0 nmol of P-450/mg of protein, respectively,
      from small intestine mucosa microsomes of rabbits. P-450id and P-450ie showed
      apparent molecular weights of 50 and 49 kDa, respectively, on SDS-PAGE. Both P
      450s catalyzed N-demethylation of nitrosodimethylamine. The NH2-terminal amino
      acid sequence (first 19 residues) of P-450id exhibited 74-90% identity with those
      of six members of the rabbit P-450 2C subfamily, except for P-450 2C3. Similarly,
      the NH2-terminal sequence (first 22 residues) of P-450ie showed 73-86% identity
      with those of the same members of the rabbit P-450 2C subfamily. The peptide
      mapping patterns of the two P-450s were quite different from each other. In
      addition, P-450id did not cross-react with the guinea-pig antibodies against P
      450ie. The results indicate that rabbit small intestine mucosa contain two new
      distinct forms of P-450s, both of which may be classified into the 2C subfamily.

PMID- 9187248
TI  - High salt concentrations induce dissociation of dimeric rabbit muscle creatine
      kinase. Physico-chemical characterization of the monomeric species.
AB  - Incubation of dimeric MM-creatine kinase (MM-CK) with high NaCl or LiCl
      concentrations results in dissociation of the subunits and complete enzyme
      inactivation. In NaCl, this process, which depends on protein concentration, may
      be described according to a two-state model where the dimer can be reversibly
      converted into compact folded monomers (D <--> 2M). At LiCl concentrations higher
      than 2-2.5 M, MM-CK is recovered in two monomeric states: an inactive compact
      species (M) and a more expanded form (EF), which represents 15-20% of the
      population. Thus, in LiCl, a three-state model (D <--> 2M --> 2EF) more
      adequately accounts for our experimental results. The monomeric species (M)
      obtained in NaCl and LiCl exhibits some properties of the molten globule state
      described in guanidine hydrochloride. Indeed, this form is compact and devoid of
      any enzymatic activity; it maintains a high degree of secondary structure and
      binds 8-anilino-1-naphthalenesulfonate. The formation of this intermediate
      induces the exposure of a second tryptophan (among the four present) which is
      located at the monomer-monomer interface in the native structure. In LiCl, the
      monomeric species (M) is irreversibly converted into a less compact form (EF)
      which seems to have lost a large part of its secondary structure.

PMID- 9187249
TI  - Characterisation of a xylanolytic amyloglucosidase of Termitomyces clypeatus.
AB  - A xylanolytic amyloglucosidase of Termitomyces clypeatus was characterised with
      respect to other amyloglucosidases. The enzyme contained high alpha-helix
      destabilising amino acids but no sulphur amino acid. It contained high threonine
      and serine, analogous to other raw starch hydrolysing enzymes. Both xylanase and
      amyloglucosidase activities were gradually lost with the progress of tryptophan
      oxidation by NBS and total inactivation occurred after oxidation of 4-5
      tryptophan residues. In the presence of substrates (either starch or xylan),
      complete inactivation of either activities was not noticed even after oxidation
      of 7.7 mol of tryptophan residues. Inactivation by HNBB was not possible in the
      absence of any denaturant. Only 4.9 mol of tryptophan could be modified in the
      presence of 5 M urea which resulted in only 42% inhibition of activity. Thus
      modified enzyme had higher Vm/Km and lower pH optima in comparison to those of
      native enzyme. It was suggested that tryptophan was present at the substrate
      binding site and not at the active site. No such change in activity was noticed
      after modification of tyrosine, lysine or arginine residues. HPGPLC analysis of
      both dilute and concentrated enzyme solution indicated that the enzyme existed as
      an equilibrium mixture of protomer-oligomer. Perhaps for this reason molar mass
      of NAI modified enzyme appeared to be almost half of that modified by NAI in
      presence of substrate. Arrhenius plot of the enzyme also indicated reversible
      oligomerisation as a function of temperature.

PMID- 9187250
TI  - Kinetic study of the suicide inactivation of latent polyphenoloxidase from
      iceberg lettuce (Lactuca sativa) induced by 4-tert-butylcatechol in the presence
      of SDS.
AB  - In plants, polyphenoloxidase undergoes an irreversible inactivation during the
      oxidation of o-diphenol to o-quinones. In the present paper, using latent
      polyphenoloxidase from iceberg lettuce (Lactuca sativa), in the presence of an
      activating agent, SDS, the kinetic parameters that characterize the enzyme during
      its action on the suicide substrate 4-tert-butylcatechol have been determined.
      The effect of pH has also been considered. It was seen that the presence of SDS
      in the reaction medium changed the kinetic parameters of the enzyme during
      suicide inactivation, this phenomenon depended on the SDS concentration up to
      saturating concentrations. Variations were also observed in the kinetic
      parameters at pH values below 5 where SDS provoked inactivation of the enzyme.
      This differing kinetic behaviour during suicide inactivation in the presence of
      SDS may be caused by the conformational changes provoked by SDS in the enzyme in
      latent state. Thus, polyphenoloxidases showing suicide inactivation would present
      an enzymatic activity resulting from the balance between the activation process
      and suicide inactivation.

PMID- 9187251
TI  - Concentration and temperature dependence of viscosity in lysozyme aqueous
      solutions.
AB  - The paper presents the results of viscosity determinations on aqueous solutions
      of hen egg-white lysozyme at a wide range of concentrations and at temperatures
      ranging from 5 degrees C to 55 degrees C. It has been proved that, at each fixed
      concentration, the viscosity-temperature dependence may be quantitatively
      described by the modified Arrhenius formula. On the basis of the generalized
      Arrhenius formula, the parameters of the Mooney approximation were calculated. It
      has been concluded that lysozyme molecules in aqueous solution behave as hard
      quasi-spherical particles. By applying an asymptotic form of the generalized
      Arrhenius formula, such rheological quantities as the intrinsic viscosity and
      Huggins coefficient were calculated.

PMID- 9187252
TI  - Efficient purification, characterization and partial amino acid sequencing of two
      alpha-1,4-glucan lyases from fungi.
AB  - alpha-1,4-Glucan lyases from the fungi Morchella costata and M. vulgaris were
      purified by affinity chromatography on beta-cyclodextrin-sepharose, followed by
      ion exchange and gel filtration. The purified enzymes produced 1,5-anhydro-D
      fructose from glucose oligomers and polymers with alpha-1,4-glucosidic linkages,
      such as maltose, maltosaccharides, amylopectin, and glycogen. The lyases were
      basically inactive towards glucans linked through alpha-1,1, alpha-1,3 or alpha
      1,6 linkages. For both enzymes the molecular mass was around 121,000 Da as
      determined by matrix-assisted laser desorption mass spectrometry. The pI for the
      lyases from M. costata and M. vulgaris was 4.5 and 4.4, respectively. The lyases
      exhibited an optimal pH range of pH 5.5 to pH 7.5 with maximal activity at pH
      6.5. Optimal temperature was between 37 degrees C and 48 degrees C for the two
      lyases, depending on the substrates. The lyases were examined with 12 inhibitors
      to starch hydrolases and it was found that they were inhibited by the -SH group
      blocking agent PCMB and the following sugars and their analogues: glucose,
      maltitol, maltose, 1-deoxynojirimycin and acarbose. Partial amino acid sequences
      accounting for about 35% of the lyase polypeptides were determined. In the
      overlapping region of the sequences, the two lyases showed 91% identity. The two
      lyases also cross-reacted immunologically.

PMID- 9187253
TI  - Photoaffinity labeling of peroxisome proliferator binding proteins in rat
      hepatocytes; dehydroepiandrosterone sulfate- and bezafibrate-binding proteins.
AB  - To detect the cellular sites which directly interact with peroxisome
      proliferators (PPs) and mediate their inducing effect on peroxisomal enzymes in
      rat hepatocytes, two kinds of radiolabeled ligands, AD12 (7alpha-N-(4-azido-2
      hydroxy-5-iodo[125I]benzyl)-aminomethyl-5-and rostene-3beta-ol-17-one-O-3
      sulfate) and BZ5 (2-[p-[2-(4'-azido-3',5'-diiodo[125I]benzamido-2'
      hydroxy)ethyl]phenoxy] -2-methylpropionic acid), were developed for photoaffinity
      labeling. These compounds were derivatives of dehydroepiandrosterone sulfate
      (DHEAS) and bezafibrate, respectively, with an azido group as the photoreactive
      functional group. Upon UV-irradiation following incubation with rat liver cytosol
      and nuclei, both the ligands effectively radiolabeled several proteins analyzed
      by SDS-polyacrylamide gel electrophoresis/radioluminography. When [125I]AD12 was
      used at a concentration of 0.2 microM, two cytosolic proteins with molecular
      masses of 55 and 28 kDa and a nuclear protein of 40 kDa were specifically
      labeled, as coincubation with a 1000-fold excess of DHEAS inhibited labeling.
      Photoaffinity labeling of the cytosolic 28-kDa protein was also affected by Wy
      14,643, but not by unsulfated dehydroepiandrosterone or androsterone sulfate,
      consistent with our previous findings obtained in competitive binding studies of
      [3H]DHEAS-binding detected in rat liver cytosol (Yamada et al. (1994) Biochim.
      Biophys. Acta 1224, 139-146). On the other hand, [125I]BZ5 specifically labeled a
      cytosolic protein of 31 kDa, which was inhibited by coincubation with
      bezafibrate, clofibric acid and Wy-14,643, but not with DHEAS. Thus, [125I]AD12
      and [125I]BZ5 labeled several proteins which recognized DHEAS and bezafibrate,
      respectively, in rat liver cytosol and nuclei, providing a useful means to
      investigate PP-binding proteins.

PMID- 9187254
TI  - Effects of profilin-annexin I association on some properties of both profilin and
      annexin I: modification of the inhibitory activity of profilin on actin
      polymerization and inhibition of the self-association of annexin I and its
      interactions with liposomes.
AB  - We have previously shown that annexin I, a member of a family of calcium
      dependent phospholipid and membrane binding proteins, interacts with profilin
      with high specificity and affinity. This finding further suggests that annexin I
      is involved through profilin in the regulation of membrane-cytoskeleton
      organization. We have investigated the consequences of a complex formed by these
      two proteins on the functions of both profilin and annexin I. Annexin I is able
      to modify the inhibitory effect of profilin on actin polymerization. This action
      is partial and the mechanism involved appears to be complex. On the other hand,
      the association between annexin I and profilin is sufficiently strong to inhibit
      the self-association of annexin I. The binding capacity of annexin I to liposomes
      containing phosphatidylserine, which mimics annexin I binding to membranes, is
      also decreased by profilin. This binding is nevertheless restored when
      phosphatidylinositol 4,5-biphosphate (PtdInsP2) is included in the liposomes.
      Finally, the capacity of annexin I to aggregate liposomes is also modified. It is
      worthwhile mentioning that the liposomes-binding and liposomes-aggregating
      activities of annexin I are independently regulated. The cell localization and
      functions of annexin I and profilin suggest that interaction between these two
      proteins may be directly implicated in the regulation of membrane-cytoskeleton.
      The phospholipid composition of membranes may be one of the modulating factors.

PMID- 9187255
TI  - Programmed cell death in neurons: focus on the pathway of nerve growth factor
      deprivation-induced death of sympathetic neurons.
AB  - Extensive programmed cell death (PCD) occurs in the developing nervous system.
      Neuronal death occurs, at least in part, because neurons are produced in excess
      during development and compete with each other for the limited amounts of the
      survival-promoting trophic factors secreted by target tissues. Neuronal death is
      apoptotic and utilizes components that are conserved in other PCD pathways. In
      this review, we discuss the mechanism of trophic factor-dependent neuronal cell
      death by focusing on the pathway of nerve growth factor (NGF) deprivation-induced
      sympathetic neuronal death. We describe the biochemical and genetic events that
      occur in NGF-deprived sympathetic neurons undergoing PCD. Participation of the
      Bcl-2 family of proteins and the interleukin-1beta-converting enzyme family of
      proteases (caspases) in this and other models of neuronal death is also examined.
      The order and importance of these components during NGF deprivation-induced
      sympathetic neuronal death are discussed.

PMID- 9187256
TI  - Sodium salicylate inhibits cyclo-oxygenase-2 activity independently of
      transcription factor (nuclear factor kappaB) activation: role of arachidonic
      acid.
AB  - Acetylsalicylic acid (aspirin) is the drug most commonly self-administered to
      reduce inflammation, swelling, and pain. The established mechanism of action of
      aspirin is inhibition of the enzyme cyclo-oxygenase (COX). Once taken, aspirin is
      rapidly deacetylated to form salicylic acid, which may account, at least in part,
      for the therapeutic actions of aspirin. However, where tested, salicylic acid has
      been found to be a relatively inactive inhibitor of COX activity in vitro,
      despite being an effective inhibitor of prostanoids formed at the site of
      inflammation in vivo. Recently, the identification of a cytokine-inducible
      isoform of COX, COX-2, has led to the suggestion that salicylate produces its
      anti-inflammatory actions by inhibiting COX-2 induction through actions on
      nuclear factor kappaB (NF-kappaB). We have used interleukin 1beta-induced COX-2
      in human A549 cells to investigate the mechanism of action of salicylate on COX-2
      activity. Sodium salicylate inhibited prostaglandin E2 release when added
      together with interleukin 1beta for 24 hr with an IC50 value of 5 microg/ml, an
      effect that was independent of NF-kappaB activation or COX-2 transcription or
      translation. Sodium salicylate acutely (30 min) also caused a concentration
      dependent inhibition of COX-2 activity measured in the presence of 0, 1, or 10
      microM exogenous arachidonic acid. In contrast, when exogenous arachidonic acid
      was increased to 30 microM, sodium salicylate was a very weak inhibitor of COX-2
      activity with an IC50 of >100 microg/ml. Thus, sodium salicylate is an effective
      inhibitor of COX-2 activity at concentrations far below those required to inhibit
      NF-kappaB (20 mg/ml) activation and is easily displaced by arachidonic acid.

PMID- 9187257
TI  - Cloning and functional expression of a human liver organic cation transporter.
AB  - Polyspecific organic cation transporters in the liver mediate the elimination of
      a wide array of endogenous amines and xenobiotics. In contrast to our
      understanding of the mechanisms of organic cation transport in rat liver, little
      is known about the mechanisms of organic cation transport in the human liver. We
      report the cloning, sequencing, and functional characterization of the first
      human polyspecific organic cation transporter from liver (hOCT1). hOCT1 (554
      amino acids) is 78% identical to the previously cloned organic cation transporter
      from rat, rOCT1 [Nature (Lond.) 372:549-552 (1994)]. In Xenopus laevis oocytes
      injected with the cRNA of hOCT1, the specific uptake of the organic cation 3H-1
      methyl-4-phenylpyridinium (3H-MPP+) was significantly enhanced (8-fold) over that
      in water-injected oocytes. Uptake of 3H-MPP+ was saturable (K(m) = 14.6 +/- 4.39
      microM) and sensitive to membrane potential. Both small monovalent organic
      cations such as tetraethylammonium and N1-methylnicotinamide and bulkier organic
      cations (e.g., vecuronium and decynium-22) inhibited the uptake of 3H-MPP+. In
      addition, the bile acid taurocholate inhibited the uptake of 3H-MPP+ in oocytes
      expressing hOCT1. Northern analysis demonstrated that the mRNA transcript of
      hOCT1 is expressed primarily in the human liver, whereas the mRNA transcript of
      rOCT1 is found in rat kidney, liver, intestine, and colon [Nature (Lond.) 372:549
      552 (1994)]. In comparison to rOCT1, hOCT1 exhibits notable differences in its
      kinetic characteristics and tissue distribution. The functional expression of
      hOCT1 will provide a powerful tool for elucidation of the mechanisms of organic
      cation transport in the human liver and understanding of the mechanisms involved
      in the disposition and hepatotoxicity of drugs.

PMID- 9187258
TI  - Mutations in the sixth transmembrane domain of P-glycoprotein that alter the
      pattern of cross-resistance also alter sensitivity to cyclosporin A reversal.
AB  - The expression of a P-glycoprotein (Pgp1) cDNA encoding two amino acid
      substitutions in the sixth transmembrane domain of the protein (G338A339 to
      A338P339) confers a unique cross-resistance profile that displays preferential
      resistance to actinomycin D and diminished resistance to colchicine and
      daunorubicin. We report here that this multidrug-resistant phenotype is also
      insensitive to reversal by cyclosporin A (CsA) but not verapamil (VRP). However,
      the ability of VRP to increase the accumulation of [3H]vincristine is poor in
      both wild-type and mutant transfectants. In contrast, the accumulation of
      [3H]vincristine in wild-type versus mutant transfectants in the presence of CsA
      is dramatically increased. It is the substitution of the alanine residue at
      position 339 with proline that is primarily responsible for the lowered
      sensitivity to CsA and for the altered drug accumulation levels. Both
      substitutions are required to confer the unique cross-resistance profile of the
      double mutant, although each independently confers a specific profile of its own.
      These results indicate that alterations in Pgp1 structure can differentially
      affect the activity of CsA and VRP to mediate drug accumulation in multidrug
      resistant cells and support the conclusion that the sixth transmembrane domain of
      the Pgp1 transporter plays important roles, in both the specificity of drug
      efflux and the sensitivity of the transporter to reversal agents.

PMID- 9187259
TI  - CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression,
      localization, and potential functional significance.
AB  - Our laboratory recently described a new human cytochrome P450 arachidonic acid
      epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which
      were expressed in extrahepatic tissues. Northern analysis of RNA prepared from
      the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were
      expressed primarily in the small intestine and colon. In contrast, immunoblotting
      studies using a polyclonal antibody raised against recombinant CYP2J2 showed that
      CYP2J proteins were expressed throughout the gastrointestinal tract.
      Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal
      sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed
      that CYP2J proteins were present at high levels in nerve cells of autonomic
      ganglia, epithelial cells, intestinal smooth muscle cells, and vascular
      endothelium. The distribution of this immunoreactivity was confirmed by in situ
      hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions
      prepared from human jejunum catalyzed the NADPH-dependent metabolism of
      arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products.
      Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal
      cytochrome P450 was provided by documenting, for the first time, the presence of
      epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass
      spectrometry. We conclude that human and rat intestine contain an arachidonic
      acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic
      ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium.
      In addition to the known effects on intestinal vascular tone, we speculate that
      CYP2J products may be involved in the release of intestinal neuropeptides,
      control of intestinal motility, and/or modulation of intestinal fluid/electrolyte
      transport.

PMID- 9187260
TI  - Gadolinium chloride blocks alcohol-dependent liver toxicity in rats treated
      chronically with intragastric alcohol despite the induction of CYP2E1.
AB  - Hepatic CYP2E1 is induced in several models of alcohol administration, but
      clinically relevant pathology is only observed in rats in a model involving the
      continuous intragastric administration of an ethanol-containing, corn oil-based,
      high-fat diet. The level of CYP2E1 correlates with the degree of liver pathology
      in the intragastric feeding model, which leads to the hypothesis that radical
      production by CYP2E1 is responsible for the pathology. Destruction of the Kupffer
      cells with gadolinium chloride (GdCl3) prevented the development of ethanol
      dependent pathology and decreased the production of radicals that appeared in the
      bile of intragastrically alcohol-fed rats. If the induction of CYP2E1 and
      subsequent formation of oxidant species by the enzyme is causative in the ethanol
      dependent hepatic pathology, then protection by GdCl3 could be due an inhibition
      of CYP2E1 induction. In the current study, ethanol-administration for 4 wk
      produced marked steatosis, necrosis, and inflammation not seen in control rats.
      Immunochemically, CYP2E1 was induced 5- to 6-fold in microsomes from the ethanol
      treated animals. Rates of p-nitrophenol and chlorzoxazone hydroxylation were
      elevated approximately 3-fold, consistent with CYP2E1 induction. When GdCl3 was
      administered with ethanol, there was a decrease of approximately 80% in Kupffer
      cell receptor expression, and there was a significant decrease in hepatic
      pathology, which confirms previous studies. However, in the ethanol and GdCl3
      treated animals, there was no significant decrease in the induction of CYP2E1.
      CYP2E1 was elevated approximately 5-fold, as estimated by immunoblot analysis,
      and rates of p-nitrophenol and chlorzoxazone hydroxylation were elevated 3- to 4
      fold in ethanol + GdCl3-treated rats. Thus, these results clearly dissociate the
      induction of CYP2E1 by intragastric infusion of ethanol from the generation of
      early alcohol-induced liver disease. It is concluded that Kupffer cells rather
      than CYP2E1 play the major role in the initiation of hepatocyte damage caused by
      alcohol.

PMID- 9187261
TI  - 2-Methoxyestradiol, an endogenous estrogen metabolite, induces apoptosis in
      endothelial cells and inhibits angiogenesis: possible role for stress-activated
      protein kinase signaling pathway and Fas expression.
AB  - 2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol-17beta and the
      oral contraceptive agent 17-ethylestradiol. 2-ME was recently reported to inhibit
      endothelial cell proliferation. The current study was undertaken to explore the
      mechanism of 2-ME effects on endothelial cells, especially whether 2-ME induces
      apoptosis, a prime mechanism in tissue remodeling and angiogenesis. Cultured
      bovine pulmonary artery endothelial cells (BPAEC) exposed to 2-ME showed
      morphological (including ultrastructural) features characteristic of apoptosis:
      cell shrinkage, cytoplasmic and nuclear condensation, and cell blebbing. 2-ME
      induced apoptosis in BPAEC was a time- and concentration-dependent process (EC50
      = 0.45 +/- 0.09 microM, n = 8). Nucleosomal DNA fragmentation in BPAEC treated
      with 2-ME was identified by agarose gel electrophoresis (DNA ladder) as well as
      in situ nick end labeling. Under the same experimental conditions, estradiol
      17beta and two of its other metabolites, estriol and 2-methoxyestriol (< or =10
      microM), did not have an apoptotic effect on BPAEC. 2-ME activated stress
      activated protein kinase (SAPK)/c-Jun amino-terminal protein kinase in BPAEC in a
      concentration-dependent manner. The activity of SAPK was increased by 170 +/- 27%
      and 314 +/- 22% over the basal level in the presence of 0.4 and 2 microM 2-ME (n
      = 3-6), respectively. The activation of SAPK was detected at 10 min, peaked at 20
      min, and returned to basal levels at 60 min after exposure to 2-ME. Inhibition of
      SAPK/c-Jun amino-terminal protein kinase activation by basic fibroblast growth
      factor, insulin-like growth factor, or forskolin reduced 2-ME-induced apoptosis.
      Immunohistochemical analysis of BPAEC indicated that 2-ME up-regulated expression
      of both Fas and Bcl-2. In addition, 2-ME inhibited BPAEC migration (IC50 = 0.71
      +/- 0.11 microM, n = 4) and basic fibroblast growth factor-induced angiogenesis
      in the chick chorioallantoic membrane model. Taken together, these results
      suggest that promotion of endothelial cell apoptosis, thereby inhibiting
      endothelial cell proliferation and migration, may be a major mechanism by which 2
      ME inhibits angiogenesis.

PMID- 9187262
TI  - DNA elements recognizing NF-Y and Sp1 regulate the human multidrug-resistance
      gene promoter.
AB  - Regulation of the human multidrug resistance gene (hMDR1) was studied by mapping
      DNA elements in the proximal promoter necessary for efficient transcription.
      Transient transfection analysis in tumor cell lines (HCT116, HepG2, and Saos2) of
      promoter deletions identified several regulatory domains. These cell lines
      expressed hMDR1 mRNA. Removal of an element between +25 and +158 reduced promoter
      activity by 2-3-fold, whereas deletion of sequences from approximately -5000 to 
      138 base pairs gave a approximately 2-fold increase. The activity of the hMDR1
      promoter (-137 to +25) was comparable in activity to the SV40 early promoter and
      enhancer combination. Deletion of the hMDR1 promoter between -86 and -44 reduced
      activity by 5-10-fold, identifying an important regulatory region. This minimal
      region (-88 to -37) activated transcription when inserted upstream of a synthetic
      promoter, suggesting that it acts independently of other regulatory sequences.
      Two DNA elements within 85 base pairs of the transcriptional start site were
      required to confer efficient gene expression. A double-point mutation in the Y
      box (inverted CCAAT box) between -70 and -80 reduced activity of the promoter by
      5-10-fold, and a single-point mutation at -52 within a GC-rich element reduced
      activity by 3-fold. Thus, both the Y-box and GC elements must each remain intact
      for optimal promoter activity. DNA-binding analyses suggest that the
      transcription factor NF-Y, but not YB-1 or c/EBP, is most likely responsible for
      controlling the activity of the Y-box element in these tumor cell lines. DNA
      binding analyses also suggest that Sp1, alone or in combination with other
      nuclear factors, likely controls the activity of the GC element.

PMID- 9187263
TI  - Induction of apoptosis by retinoids and retinoic acid receptor gamma-selective
      compounds in mouse thymocytes through a novel apoptosis pathway.
AB  - Retinoic acids are morphogenic signaling molecules that are derived from vitamin
      A and involved in a variety of tissue functions. Two groups of their nuclear
      receptors have been identified: retinoic acid receptors (RARs) and retinoic acid
      X receptors (RXRs). All-trans retinoic acid is the high affinity ligand for RARs,
      and 9-cis retinoic acid also binds to RXRs with high affinity. In cells at high
      concentrations, all-trans retinoic acid can be converted to 9-cis retinoic acid
      via unknown mechanisms. It was previously shown that retinoic acids prevents
      activation-induced death of thymocytes. Here, we report that both all-trans and 9
      cis retinoic acid induce apoptosis of mouse thymocytes and purified CD4+CD8+
      cells in ex vivo cultures, with 9-cis retinoic acid being 50 times more
      effective. The induction of apoptosis by retinoic acids is mediated by RARgamma
      because (a) the phenomenon can be reproduced only by RARgamma-selective retinoic
      acid analogs, (b) the cell death induced by either retinoic acids or RARgamma
      analogs can be inhibited by RARgamma-specific antagonists, and (c) CD4+CD8+
      thymocytes express RARgamma. In vivo administration of an RARgamma analog
      resulted in thymus involution with the concomitant activation of the apoptosis
      related endonuclease and induction of tissue transglutaminase. The RARgamma
      pathway of apoptosis is RNA and protein synthesis dependent, affects the CD4+CD8+
      double positive thymocytes, and can be inhibited by the addition of either Ca2+
      chelators or protease inhibitors. Using various RAR- and RXR-specific analogs and
      antagonists, it was demonstrated that stimulation of RAR alpha inhibits the
      RARgamma-specific death pathway (which explains the lack of apoptosis stimulatory
      effects of all-trans retinoic acid at physiological concentrations) and that
      costimulation of the RXR receptors (in the case of 9-cis retinoic acid) can
      neutralize this inhibitory effect. It is suggested that formation of 9-cis
      retinoic acid may be a critical element in regulating both the positive selection
      and the "default cell death pathway" of thymocytes.

PMID- 9187264
TI  - Histamine modulates the expression of c-fos through cyclic AMP production via the
      H2 receptor in the human promonocytic cell line U937.
AB  - We examined the effects of histamine and its agonists on the expression of the c
      fos and c-myc proto-oncogenes at the transcriptional and translational levels in
      the human promonocytic U937 cell line. Histamine transiently increased cAMP and c
      fos expression through H2 receptors. Dibutyryl cAMP also increased c-fos mRNA and
      protein, and levels remained elevated even after 12 hr of treatment. Dose
      dependence studies using histamine and dimaprit showed that the EC50 values for
      cAMP production and c-fos increase were similar, suggesting that cAMP might be
      involved in c-fos induction via H2 receptors. Furthermore, studies carried out
      using H7, a protein kinase A/protein kinase C inhibitor, blocked c-fos induction,
      whereas no effect was observed with bisindolylmaleimide, a specific protein
      kinase C inhibitor. No modification of c-myc expression could be detected on
      treatment with histamine or its analogues. Nevertheless, dibutyryl cAMP induced a
      down-regulation of the levels of this proto-oncogene. In addition, dibutyryl cAMP
      inhibited cell growth in a dose-dependent manner, whereas histamine failed to
      affect proliferation and differentiation of U937 cells. Cells pretreated with
      dimaprit showed a decrease in the cAMP response to subsequent addition of H2
      agonists, whereas the cAMP response to prostaglandin E2 remained unaltered. This
      homologous mechanism of H2 receptor desensitization was time dependent. These
      results indicate that histamine activates several mechanisms involved in the
      induction of differentiation, such as cAMP and c-fos production, but fails to
      promote differentiation of U937 cells, apparently due to the rapid
      desensitization of H2 receptors.

PMID- 9187266
TI  - Role of conserved histidines in catalytic activity and inhibitor binding of human
      recombinant phosphodiesterase 4A.
AB  - To identify critical amino acids within the central conserved region of
      recombinant human cAMP-specific phosphodiesterase 4 subtype A (rhPDE4A), we
      engineered the expression of point mutants in a fully active rhPDE4A/Met201-886.
      When histidine residues at positions 433, 437, 473, and 477, which are highly
      conserved among all PDE families, were changed independently to serine residues,
      cAMP hydrolyzing activities were substantially reduced or abolished. The ability
      of these mutants to bind prototypical PDE4 inhibitors [3H]-(R)-rolipram or [3H]RP
      73401 was also decreased in parallel with the loss of catalytic activity. The
      parallel loss of catalytic activity and inhibitor binding suggests that these
      changes resulted from non-localized perturbations in the structure of the enzyme.
      More interesting results were obtained when histidine residues at positions 505
      and 506 were changed independently to aspar agines. The K(m) value for cAMP
      increased 3-fold in H505N (K(m) = 11 +/- 3 microM) and 11-fold in H506N (K(m) =
      44 +/- 6 microM) compared with the wild-type protein (K(m) = 4 +/- 1 microM).
      These mutant proteins bound [3H]-(R)-rolipram and [3H]RP 73401 with K(d) values
      of 1.8 +/- 0.4 and 0.3 +/- 0.1 nM, respectively, for H505N, and 3.9 +/- 0.9 and
      0.5 +/- 0.1 nM, respectively, for H506N. These values are nearly identical to
      those obtained with the wild-type rhPDE4A/Met201-886. In contrast, the IC50
      values for cAMP competition with either [3H]-(R)-rolipram or [3H]RP 73401 binding
      increased approximately 2-fold in H505N and approximately 13-fold in H506N
      compared with the wild type protein. These increases are virtually identical to
      the changes in the K(m) value for cAMP in these mutants. We conclude that His506
      and, perhaps, His505 are involved in binding of cAMP to PDE4A/Met201-886 but not
      in binding of PDE4-selective inhibitors.

PMID- 9187265
TI  - A dominant negative mutant of the G protein-coupled receptor kinase 2 selectively
      attenuates adenosine A2 receptor desensitization.
AB  - G protein-coupled receptor kinases (GRKs) are thought to be important in
      mediating the agonist-induced phosphorylation and consequent desensitization of G
      protein-coupled receptor responses. NG108-15 mouse neuroblastoma X rat glioma
      cells express a wide range of G protein-coupled receptors and significant levels
      of GRK2. Therefore, to determine the role of GRK2 in agonist-induced
      desensitization of various G(s)-coupled receptors in NG108-15 cells, we stably
      transfected cells with a dominant negative mutant GRK2 construct (Lys220Arg). In
      homogenates prepared from cells overexpressing the dominant negative mutant GRK2,
      the acute stimulation of adenylyl cyclase by various receptor and nonreceptor
      agonists was the same as in control cells stably transfected with plasmid only.
      NG108-15 cells express both A2a and A2b adenosine receptors, which mediate
      activation of adenylyl cyclase, with both of these responses being subject to
      agonist-induced desensitization with a t1/2 of 15-20 min. In dominant negative
      mutant GRK2 cells, the rates of desensitization of A2a and A2b receptor
      stimulated adenylyl cyclase were markedly slower than in plasmid transfected
      controls, with the latter being similar to wild-type cells. After a 20-min
      treatment with an adenosine agonist, the desensitization of A2a and A2b receptor
      stimulated adenylyl cyclase in dominant negative mutant GRK2 cells was less than
      half that seen in plasmid transfected control cells. On the other hand, the
      agonist-induced desensitization of secretin and IP-prostanoid receptor-stimulated
      adenylyl cyclase was the same in dominant negative mutant GRK2 cells as in
      plasmid transfected control cells. These results indicate that in intact cells,
      GRK2 may mediate the desensitization of adenosine A2 receptors. Furthermore,
      there seems to be selectivity of GRK2 action between G(s)-coupled receptors
      because the agonist-induced desensitization of secretin and IP-prostanoid
      receptor-stimulated adenylyl cyclase was not affected by dominant negative mutant
      GRK2 overexpression.

PMID- 9187267
TI  - Stimulatory roles of muscarinic acetylcholine receptors on T cell antigen
      receptor/CD3 complex-mediated interleukin-2 production in human peripheral blood
      lymphocytes.
AB  - It is known that there are some bidirectional interactions between the nervous
      and the immune systems via neurotransmitters and cytokines. To clarify whether
      any neurotransmitters modulate lymphocyte functions, we examined the effects of
      oxotremorine-M (Oxo-M) on interleukin-2 (IL-2) production in human peripheral
      blood lymphocytes by using enzyme-linked immunosorbent assays, Northern blot
      analyses, reverse transcriptase-polymerase chain reaction, and fluorescence
      activated cell sorter. Pretreatment of cells with Oxo-M (10 nM to 10 microM) for
      4-24 hr enhanced phytohemagglutinin (PHA)-induced IL-2 mRNA expression and
      markedly increased IL-2 production compared with those induced by PHA alone. Oxo
      M alone did not affect IL-2 mRNA expression and IL-2 production. In CD3-positive
      T cells, pretreatment with Oxo-M for 24 hr enhanced PHA-induced IL-2 production.
      Furthermore, pretreatment with Oxo-M enhanced PHA-induced mRNA expression of the
      alpha and beta subunits of IL-2 receptors and DNA synthesis. Cytometric analysis
      showed Oxo-M treatment did not up-regulate expression of cell surface molecules
      such as CD3, CD2, CD4, CD8, and IL-2 receptors. These results suggest that
      activation of muscarinic receptors enhances T cell antigen receptor/CD3-induced
      IL-2 production.

PMID- 9187268
TI  - Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to
      zinc inhibition.
AB  - Zinc has been shown to be present in synaptic vesicles of a subset of
      glutamatergic boutons and is believed to be core-leased with glutamate at these
      synapses. A variety of studies have suggested that zinc might play a role in
      modulation of excitatory transmission, as well as excitotoxicity, by inhibiting N
      methyl-D-aspartate (NMDA)-type glutamate receptors. To further investigate the
      modulatory effects of zinc on NMDA receptors of different subunit compositions,
      we coexpressed the recombinant subunit NR1 with NR2A and/or NR2B in HEK 293
      cells. In whole-cell patch-clamp recordings from these transfected cells, zinc
      inhibited peak glutamate-evoked current responses in a noncompetitive manner, but
      there were significant differences between the receptor subtypes in sensitivity
      to zinc inhibition. For NR1/NR2A, approximately 40% of the peak current was
      inhibited by zinc in a voltage-independent manner with an IC50 value of 5.0 +/-
      1.6 nM and at a V(H) value of -60 mV; the remainder was blocked at a second,
      voltage-dependent site with an IC50 value of 79 +/- 18 microM. In contrast,
      NR1/NR2B currents showed nearly complete inhibition at a voltage-independent site
      with an IC50 value of 9.5 +/- 3.3 microM. Cells cotransfected with NR1, NR2A, and
      NR2B showed zinc sensitivity intermediate between that characteristic of NR1/NR2A
      and that of NR1/NR2B. Furthermore, zinc accelerated the macroscopic
      desensitization of both NR1/NR2A and NR1/NR2B in a dose-dependent manner,
      apparently independently of glycine-sensitive desensitization and Ca2(+)
      dependent inactivation; maximal effects were to decrease desensitization time
      constants for NR1/NR2A by approximately 75% and for NR1/NR2B by approximately
      90%. Differential modulation of NR1/NR2A and NR1/NR2B currents by zinc may play a
      role in regulating NMDA receptor-induced synaptic plasticity and neurotoxicity.

PMID- 9187269
TI  - P-glycoprotein substrates and antagonists cluster into two distinct groups.
AB  - To gather further insight into the interaction between P-glycoprotein (Pgp) and
      its substrates, 167 compounds were analyzed in multidrug resistant human colon
      carcinoma cells. These compounds were selected from the National Cancer Institute
      Drug Screen repository using computer-generated correlations with known Pgp
      substrates and antagonists. The compounds were prospectively defined as Pgp
      substrates if cytotoxicity was increased > or =4-fold by the addition of
      cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased
      rhodamine accumulation by 4-fold. Among the 84 agents that met either criterion,
      35 met only the criterion for substrates, 42 met only the criterion for
      antagonists, and only seven met both criteria. Thus, compounds interacting with
      Pgp form two distinct groups: one comprising cytotoxic compounds that are
      transported and have poor or no antagonistic activity and a second comprising
      compounds with antagonistic activity and no evidence of significant transport.
      Vinblastine accumulation and kinetic studies performed on a subset of 18
      compounds similarly differentiated substrates and antagonists, but inhibition of
      3H-azidopine labeling and induction of ATPase activity did not. These data
      support an emerging concept of Pgp in which multiple regions instead of specific
      sites are involved in drug transport.

PMID- 9187271
TI  - Purification of a new dimeric protein from Cliona vastifica sponge, which
      specifically blocks a non-L-type calcium channel in mouse duodenal myocytes.
AB  - Marine sponges are synthesizing a wide variety of peptidic and organic molecules
      with biological activities. Multiple-step purification of Cliona vastifica
      extract led to a new dimeric peptide (mapacalcine; M(r) = 19,064) that is
      composed of two homologous chains, each containing nine cysteins. This protein
      has been found to selectively block a new calcium conductance characterized in
      mouse duodenal myocytes with an IC50 value of approximately 0.2 microM. The
      mapacalcine-sensitive current was a non-L-type calcium current activated from a
      holding potential of -80 mV that persisted during stimulation of the cell at high
      frequencies (0.1-0.2 Hz) within 5-10 min. Time constants of inactivation were
      similar for both L-type and non-L-type calcium currents. The non-L-type calcium
      current of duodenal myocytes was not blocked by the pharmacological agents
      specific for N-, L-, P-, or Q-type calcium channels. Mapacalcine was unable to
      block T-type calcium current in portal vein myocytes as well as voltage-dependent
      potassium currents and calcium-activated chloride currents in duodenal and portal
      vein cells. Mapacalcine did not affect caffeine-induced calcium responses,
      indicating that it did not interfere with intracellular calcium stores.
      Competition experiments on mouse intestinal membranes showed that mapacalcine did
      not interact with dihydropyridines receptors. These data suggest that mapacalcine
      may be a specific inhibitor of a new type of calcium current, first identified in
      duodenal myocytes.

PMID- 9187270
TI  - ATP-dependent transport of aflatoxin B1 and its glutathione conjugates by the
      product of the multidrug resistance protein (MRP) gene.
AB  - Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin
      B1-8,9-epoxide plays an important role in preventing binding of this ultimate
      carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH
      conjugates are actively extruded from the cell by an unidentified ATP-dependent
      export pump or pumps. Two possible candidates for this GSH conjugate pump are the
      190-kDa multidrug resistance protein (MRP) and the 170-kDa P-glycoprotein. Both
      proteins belong to the ATP-binding cassette superfamily of transmembrane
      transport proteins and confer resistance to a similar spectrum of natural-product
      drugs. Using membrane vesicles from MRP-transfected cells, we found that MRP
      transports GSH conjugates of both the endo-isomers and exo-isomers of aflatoxin
      B1-8,9-epoxide in an ATP-dependent, osmotically sensitive manner (V(max) = 180
      pmol/mg/min, K(m) = 189 nM). Membrane vesicles from P-glycoprotein-overexpressing
      cells showed very low levels of transport. MRP-mediated transport was inhibited
      by an MRP-specific monoclonal antibody and by a variety of GSH derivatives and
      cholestatic steroid glucuronides. ATP-dependent transport of unmodified aflatoxin
      B1 by MRP-enriched membrane vesicles was low but markedly enhanced in the
      presence of 5 mM GSH, even though GSH conjugates of aflatoxin B1 were not formed
      by the vesicles. These data demonstrate that MRP is capable of energy-dependent
      transport of aflatoxin B1 and its GSH conjugates and suggest a potential
      protective role for MRP in mammalian chemical carcinogenesis.

PMID- 9187272
TI  - Relationship between lethal effects and topoisomerase II-mediated double-stranded
      DNA breaks produced by anthracyclines with different sequence specificity.
AB  - The role of the site selectivity of topoisomerase II poisoning in the cytotoxic
      activity of anthracyclines has not been established. In this article, we have
      thus studied the levels and persistence of double-stranded DNA breaks (DSB) along
      with the cytotoxic activity in human leukemic HL60 cells of seven anthracyclines,
      including doxorubicin, daunorubicin, and idarubicin, as well as sugar-modified
      analogues characterized by an altered sequence specificity. Epimerization at the
      3' position of the sugar moiety markedly affected the biological activity;
      indeed, a dramatic reduction of drug effects was evident for 3'-deamino-3'-epi
      hydroxy-4'-deoxy-4'-amino-daunorubicin. The studied analogues could be gathered
      into three groups based on the DSB/cytotoxicity ratio. At equitoxic
      concentrations: (a) parent drugs and 3'-deamino-3'-epi-hydroxy-4'-deoxy-4'-amino
      daunorubicin endowed with the same sequence specificity stimulated low DSB
      levels; (b) 3'-epi-daunorubicin and 3'-deamino-4'-deoxy-4'-epi-amino-idarubicin,
      which have a different sequence specificity, and teniposide (a structurally
      unrelated poison) stimulated higher amounts of DSB; and (c) 4-demethoxy-3'
      deamino-3'-hydroxy-4'-epi-doxorubicin stimulated the highest DSB levels. For the
      last agent, a faster rate of cleavage resealing, which is consistent with a
      reduced DNA binding affinity, could account for the increased DSB/cytotoxicity
      ratio compared with parent drugs. However, for other analogues, the observed
      differences in DSB persistence/resealing could not completely explain the
      different DSB/cytotoxicity ratios. The results thus suggest that the cytotoxic
      potency of anthracyclines may be the result of an interplay of the level, the
      persistence, and the genomic localization of topoisomerase II-mediated DNA
      cleavage.

PMID- 9187273
TI  - Somatostatin5 receptor-mediated [35S]guanosine-5'-O-(3-thio)triphosphate binding:
      agonist potencies and the influence of sodium chloride on intrinsic activity.
AB  - We studied the activation of the human somatostatin5 receptor recombinantly
      expressed in CHO-K1 cells by using some newly available agonists and antagonists.
      Somatostatin-28 bound to this receptor with a higher affinity than somatostatin
      14 and was more potent in increasing [35S]guanosine-5'-O-(3-thio)triphosphate
      ([35S]GTPgammaS) binding. Somatostatin-14-induced [35S]GTPgammaS binding to
      membranes from this cell line was decreased in a concentration-related manner by
      increasing concentrations of GDP and sodium chloride. At 50 mM (low) sodium,
      agonist EC50 values for stimulating [35S]GTPgammaS binding were lower than those
      at 150 mM (high) sodium and were closer to their respective affinity estimates
      (dissociation equilibrium constants) for binding to the receptor in the absence
      of sodium. Both agonist binding to the high affinity state of the receptor and
      agonist-induced [35S]GTPgammaS binding were abolished by pertussis toxin
      pretreatment. The putative somatostatin5 receptor-selective ligand L-362,855,
      unlike somatostatin-14 and somatostatin-28, showed differential intrinsic
      activity for stimulation of [35S]GTPgammaS binding, behaving as a partial agonist
      in high sodium and a full agonist in low sodium. In contrast, BIM-23056 did not
      behave as an agonist under any conditions studied but was able to antagonize
      somatostatin-14-induced [35S]GTPgammaS binding. We conclude that measurement of
      [35S]GTPgammaS binding mediated by somatostatin receptor activation in the
      presence of different concentrations of sodium chloride provides a useful
      functional assay for assessing the relative agonist efficacies of novel ligands
      identified from radioligand binding studies.

PMID- 9187274
TI  - Substrate dependence of angiotensin I-converting enzyme inhibition: captopril
      displays a partial selectivity for inhibition of N-acetyl-seryl-aspartyl-lysyl
      proline hydrolysis compared with that of angiotensin I.
AB  - Angiotensin I-converting enzyme (ACE) is composed of two highly similar domains
      (referred to here as the N and C domains) that play a central role in blood
      pressure regulation; ACE inhibitors are widely used in the treatment of
      hypertension. However, the negative regulator of hematopoiesis, N-acetyl-seryl
      aspartyl-lysyl-prolyl (AcSDKP), is a specific substrate of the N domain-active
      site; thus, in addition to the cardiovascular function of ACE, the enzyme may be
      involved in hematopoietic stem cell regulation, raising the interest of designing
      N domain-specific ACE inhibitors. We analyzed the inhibition of angiotensin I and
      AcSDKP hydrolysis as well as that of three synthetic ACE substrates by wild-type
      ACE and the N and C domains by using a range of specific ACE inhibitors. We
      demonstrate that captopril, lisinopril, and fosinoprilat are potent inhibitors of
      AcSDKP hydrolysis by wild-type ACE, with K(i) values in the subnanomolar range.
      However, of the inhibitors tested, captopril is the only compound able to
      differentiate to some degree between AcSDKP and angiotensin I inhibition of
      hydrolysis by wild-type ACE: the K(i) value with AcSDKP as substrate was 16-fold
      lower than that with angiotensin I as substrate. This raises the possibility of
      using captopril to enhance plasma AcSDKP levels with the aim of normal
      hematopoeitic stem cell protection during chemotherapy and a limited effect on
      the cardiovascular function of ACE.

PMID- 9187275
TI  - Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from
      phenytoin and possible therapeutic implications.
AB  - Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic
      drugs, have been proposed to share a similar mechanism of action by use-dependent
      inhibition of Na+ channels. The proposed similar mechanism of action, however,
      cannot explain the common clinical experiences that the two drugs are different;
      in some patients, one drug may be more effective than the other. This may occur
      even when optimal therapeutic concentrations are reached with both medications in
      plasma or the cerebrospinal fluid. In this study, we show that the action of the
      two drugs on Na+ channels are quantitatively very different. The affinity between
      inactivated Na+ channels and carbamazepine (apparent dissociation constant
      approximately 25 microM) is approximately 3 times lower than that of phenytoin,
      yet the binding rate constant of carbamazepine onto the inactivated Na+ channels
      is approximately 38,000 M(-1)/sec(-1), or approximately 5 times faster than that
      of phenytoin. It is speculated that carbamazepine may be more effective than
      phenytoin in treating seizures whose ictal depolarization shift is relatively
      short, whereas a better response to phenytoin may imply abnormal discharges
      characterized by more prolonged depolarization.

PMID- 9187276
TI  - A quantitative analysis of the glial cell reaction in primary sensory termination
      areas following sciatic nerve injury and treatment with nerve growth factor in
      the adult rat.
AB  - The time course of the astroglial cell reaction in the nucleus gracilis and the
      spinal cord dorsal horn was examined following sciatic nerve transection in the
      adult rat with qualitative and quantitative analysis of glial fibrillary acidic
      protein immunoreactivity and in situ hybridization for its mRNA. In addition, the
      potential effect of exogenous nerve growth factor (NGF) was examined on the
      astroglial and microglial cells in the spinal cord dorsal horn at certain time
      points following sciatic nerve transection. An increase in glial fibrillary
      acidic protein immunoreactivity as well as mRNA labelling was observed from 1 day
      after lesioning, with a peak at about 1 week and 2 days after lesioning,
      respectively, followed by a decline. However, NGF application during 1, 2 and 4
      weeks following nerve transection did not result in any significantly reduced
      astroglial or microglial activity. Our results show that the astroglial cell
      response in the nucleus gracilis and the spinal cord dorsal horn is rapid in
      comparison with previously described central degenerative changes following
      peripheral nerve lesions (transganglionic degeneration), that the astroglial cell
      reaction develops concomitantly with the microglial cell reaction previously
      described and that the "signal" from the axotomized neurons which induces these
      reactions can not be prevented by exogenous NGF applied to the peripheral nerve.

PMID- 9187277
TI  - Contributions of regularly and irregularly discharging vestibular-nerve inputs to
      the discharge of central vestibular neurons in the alert squirrel monkey.
AB  - The discharge of neurons in the vestibular nuclei was recorded in alert squirrel
      monkeys while they were being sinusoidally rotated at 2 Hz. Type I position
      vestibular-pause (PVP I) and vestibular-only (V I) neurons, as well as a smaller
      number of other type I and type II eye-plus-vestibular neurons were studied. Many
      of the neurons were monosynaptically related to the ipsilateral vestibular nerve.
      Eye-position and vestibular components of the rotation response were separated by
      multiple regression. Anodal currents, simultaneously delivered to both ears, were
      used to eliminate the head-rotation signals of irregularly discharging (I)
      vestibular-nerve afferents, presumably without affecting the corresponding
      signals of regularly discharging (R) afferents. R and I inputs to individual
      central neurons were determined by comparing rotation responses with and without
      the anodal currents. The bilateral currents, while reducing the background
      discharge of all types of neurons, did not affect the mean vestibular gain or
      phase calculated from a population of PVP I neurons or from a mixed population
      consisting of all type I units. From this result, it is concluded that I inputs
      are canceled at the level of secondary neurons. The cancellation may explain why
      the ablating currents do not affect the gain and phase of the vestibulo-ocular
      reflex. While cancellation was nearly perfect on a population basis, it was less
      so in individual neurons. For some neurons, the ablating currents decreased
      vestibular gain, while for other neurons the vestibular gain was increased. The
      former neurons are interpreted as receiving a net excitatory (I-EXC) I input, the
      latter neurons, a net inhibitory (I-INH) input. When compared with the
      corresponding R inputs, the I inputs were usually small and phase advanced. Phase
      advances were larger for I-EXC than for I-INH inputs. The sign and magnitude of
      the I inputs were unrelated to other discharge properties of individual neurons,
      including discharge regularity and the phase of vestibular responses measured in
      the absence of the ablating currents. Unilateral currents were used to assess the
      efficacy of ipsilateral and contralateral pathways. Ipsilateral pathways were
      responsible for almost all of the effects seen with bilateral currents. The
      results suggest that the vestibular signals carried by central neurons, even by
      those neurons receiving a monosynaptic vestibular-nerve input, are modified by
      polysynaptic pathways.

PMID- 9187278
TI  - Septal innervation of mossy cells in the hilus of the rat dentate gyrus: an
      anterograde tracing and intracellular labeling study.
AB  - Mossy cells in the hilus of the rat dentate gyrus are the main cells of origin of
      the dentate commissural and associational projections. They project along the
      septotemporal axis of the dentate gyrus and may thus influence the hippocampal
      signal flow in a longitudinal direction. To analyze the septal innervation of
      these hilar neurons, anterograde tracing with Phaseolus vulgaris leucoagglutinin
      (PHAL) was used in combination with intracellular labeling of mossy cells
      (Lucifer yellow). Anterogradely labeled septal fibers impinge on proximal and
      distal dendrites of hilar mossy cells but spare the cell body. In contrast,
      numerous aspiny hilar neurons, presumably GABAergic interneurons, receive a
      septal innervation on their somata and proximal primary dendrites. These data
      demonstrate that septal fibers show a specificity for the dendritic segments of
      hilar mossy cells. Since mossy cells project predominantly to adjacent
      hippocampal lamellae, the activity of adjacent portions of the dentate gyrus may
      be influenced by the septal input onto these neurons.

PMID- 9187279
TI  - Cocaine administration in pregnant rabbits alters cortical structure and function
      in their progeny in the absence of maternal seizures.
AB  - Previous studies have reported that cocaine exposure in utero results in
      structural and functional alterations in the development of the anterior
      cingulate cortex (ACC). In the present study, the effects of maternal cocaine
      dosage and of cocaine-elicited maternal seizures on the progeny were studied. The
      incidence of maternal generalized tonic clonic seizures (GTCSs) elicited by
      cocaine was recorded. No GTCSs were elicited in pregnant rabbits by doses of 2 or
      3 mg/kg of cocaine, but GTCSs were sometimes elicited by the highest dose (4
      mg/kg per injection). We analyzed the offspring of cocaine-exposed and control
      animals using three assays of ACC development: (i) the structure of apical
      dendrites of pyramidal neurons, (ii) the distribution of a calcium binding
      protein (parvalbumin) in the dendrites of GABAergic neurons, and (iii) coupling
      of D1-like receptors and their G proteins. In all progeny of rabbits exposed to 3
      or 4 mg/kg of cocaine during pregnancy, there was a significant change in the
      structure of apical dendrites, a significant increase in the number of dendrites
      of GABAergic neurons which were parvalbumin immunoreactive, and a significant
      reduction in D1/G protein coupling. In assays of apical dendrites, the effects on
      offspring of rabbits given 2 mg/kg cocaine were as pronounced as in offspring of
      rabbits given 3 or 4 mg/kg, but the effects on parvalbumin immunoreactivity and
      D1/G protein coupling were reduced at this low dose. Thus, previous findings of
      ACC developmental abnormalities in offspring of rabbits given a dose of 4 mg/kg
      were replicated, the effects were shown to be dose-related and to be independent
      of maternal seizures. A mechanism by which dysfunction of the D1 receptor system
      could mediate cocaine-associated changes in all three parameters of ACC structure
      and function is discussed.

PMID- 9187280
TI  - Intracellular recordings from medial septal neurons during hippocampal theta
      rhythm.
AB  - The electrophysiological properties of neurons of the medial septal nucleus and
      the nucleus of the diagnonal band of Broca (MS/DB) were studied using
      intracellular methods in urethane-anesthetized rats. Three types of rhythmically
      bursting neurons were identified in vivo on the basis of their action potential
      shapes and durations, afterhyperpolarizations (AHPs), membrane characteristics,
      firing rates and sensitivities to the action of muscarinic antagonist: (1) Cells
      with short-duration action potentials and no AHPs (2 of 34 rhythmic cells, 6%)
      had high firing rates and extremely reliable bursts with 6-16 spikes per theta
      cycle, which were highly resistant to scopolamine action. (2) Cells with short
      duration action potentials and short-duration AHPs (8 of 34 rhythmic cells, 24%)
      also had high firing rates and reliable bursts with 4-13 spikes per theta cycle,
      phase-locked to the negative peak of the dentate theta wave. Hyperpolarizing
      current injection revealed a brief membrane time constant, time-dependent
      membrane rectification and a burst of firing at the break. Depolarizing current
      steps produced high-frequency repetitive trains of action potentials without
      spike frequency adaptation. The action potential and membrane and characteristics
      of this cell type are consistent with those described for GABAergic septal
      neurons. Many of these neurons retained their theta-bursting pattern in the
      presence of muscarinic antagonist. (3) Cells with long-duration action potentials
      and long-duration AHPs (24 of 34 rhythmic cells, 70%) had low firing rates, and
      usually only 1-3 spikes per theta cycle, locked mainly to the positive peak of
      the dentate theta rhythm. Hyperpolarizing current injection revealed a long
      membrane time constant and a break potential; a depolarizing pulse caused a train
      of action potentials with pronounced spike frequency adaptation. The action
      potential and membrane properties of this cell type are consistent with those
      reported for cholinergic septal neurons. The theta-related rhythmicity of this
      cell type was abolished by muscarinic antagonists. The phasic inhibition of
      "cholinergic" MS/DB neurons by "GABAergic" MS/DB neurons, followed by a rebound
      of their firing, is proposed as a mechanism contributing to recruitment of the
      whole MS/DB neuronal population into the synchronized rhythmic bursting pattern
      of activity that underlies the occurrence of the hippocampal theta rhythm.

PMID- 9187281
TI  - Neurochemical characterization of AMPA receptor-containing neurons in the
      mediolateral septal area of the rat.
AB  - The lateral septum receives a massive innervation by excitatory amino acid
      containing limbic cortical and hypothalamic afferents, and previous studies have
      described a wide distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) receptor-containing neurons in this area. The aim of this
      study was to determine whether different subtypes of AMPA receptors are expressed
      in the same neurons. Furthermore, considering the fact that a population of
      lateral septal cells, the "somatospiny neurons," are GABAergic calbindin
      containing cells, the coexistence of each subtype of AMPA receptor with calbindin
      was also investigated. Colocalization experiments were performed on adjacent
      vibratome sections of the lateral septal area for GluR1 and GluR2/3 AMPA-receptor
      subunits, GluR1 and calbindin, GluR2/3 and calbindin, as well as GluR1 plus
      calbindin and GluR2/3 plus calbindin, using the "mirror" colocalization
      technique. The results are summarized as follows: (1) GluR1 is present in the
      soma and most intensively expressed in dendrites and somatic and dendritic
      spines; while GluR2/3 is associated with the soma and proximal dendrites of the
      neurons. (2) Forty-one percent of the AMPA receptor-containing neurons cocontain
      GluR1 and GluR2/3. (3) Thirty-eight percent of GluR1- and 28% of GluR2/3-labeled
      cells express calbindin. (4) Sixty-two percent of the calbindin-immunoreactive
      neurons contain GluR1 and 51% of them express GluR2/3. (5) Half of the neurons
      expressing both GluR1 and GluR2/3 also contain calbindin. (6) The distribution of
      GluR1 plus GluR2/3-containing, GluR1 plus calbindin-containing, and GluR2/3 plus
      calbindin-containing neurons in the lateral septum are homogeneous. This study
      indicates the existence of multiple populations of AMPA receptor- and calbindin
      containing neurons in the lateral septal area.

PMID- 9187282
TI  - Topographical characteristics of preposito-collicular projections in the cat as
      revealed by Phaseolus vulgaris-leucoagglutinin technique. A possible organisation
      underlying temporal-to-spatial transformations.
AB  - A neuronal pathway from the nucleus prepositus hypoglossi (PH) to the superior
      colliculus (SC) has been documented in previous studies using retrogradely
      transported tracer methods. This pathway may underlie a feedback control of gaze
      related collicular activities. The present study provided a detailed description
      of this pathway in the cat using the Phaseolus vulgaris-leucoagglutinin
      technique. Two axonal trajectories exist that depend on the location of
      injections into the PH. As described in previous studies, injections within the
      caudal PH labelled axons that ran through the contralateral side and terminated
      in the contralateral SC (cSC). Injections in the rostral PH labelled axons
      ascending in the midbrain on the ipsilateral side and ending within both
      colliculi--mostly in the rostral SC on the ipsilateral side and over a large
      rostrocaudal extent on the contralateral side. A quantitative analysis of the
      density of synaptic terminal boutons was done in three out of six cats which
      revealed that, independently of axonal trajectories, the density of boutons
      increased from rostral to caudal in the cSC. Thus the preposito-collicular
      projection is weighted along the rostrocaudal axis of the cSC. From this result,
      a simulation was done in order to examine how excitatory sensory activities and a
      topographically weighted inhibitory feedback might interact within collicular
      networks. This simulation was able to mimic electrophysiological data obtained in
      the cat and in the monkey that showed that the motor error is topographically
      coded over the collicular map. Present results give a strong morphological
      support for a temporal-to-spatial transformation of feedback signals related to
      eye movement parameters.

PMID- 9187283
TI  - Multiple temporal components of optic flow responses in MST neurons.
AB  - Neurons in monkey medial superior temporal cortex (MST) respond to optic flow
      stimuli with early phasic, tonic, and after-phasic response components. In these
      experiments we characterized each response component to compare its potential
      contributions to visual motion processing. The early responses begin 60-100 ms
      after stimulus onset and last between 100 and 250 ms, the tonic responses begin
      100-300 ms after stimulus onset and last for as long as the evoking stimulus
      persists, and the after-responses begin about 60 ms after the stimulus goes off
      and last for 100-350 ms. A neuron's tonic responses were evoked by specific optic
      flow stimuli: over two-thirds of the 264 neurons showed tonic responses evoked by
      two to five stimuli, whereas only 15% responded to either all or none of the
      stimuli. The tonic responses continued with stimulus presentations as long as 15
      s, with their directional preferences being maintained throughout stimulation.
      However, the tonic response to a given stimulus was seen to change in amplitude
      when it was presented in random sequence with different sets of other stimuli.
      Thus, the tonic responses might convey substantial information about optic flow
      patterns, which continue with prolonged stimulation, but can be modified by the
      visual context created by other visual motion stimuli. Only about one-third of
      the 264 neurons had early responses that were selective for specific stimuli. In
      neurons yielding at least one early response, that neuron was most often
      activated by all the visual motion stimuli. After-responses occurred in only half
      the neurons, but they were more often specifically related to particular optic
      flow stimuli, regardless of whether those stimuli had evoked tonic excitatory or
      tonic inhibitory responses. The presence of early and after-responses complicates
      the interpretation of activity evoked when one stimulus immediately follows
      another. However, under those conditions, early responses and after-responses
      might contribute to signaling changes in the ongoing pattern of optic flow. We
      conclude that several components of MST responses should be recognized and that
      they potentially play different roles in the cortical analysis of optic flow.
      Tonic responses show the greatest specificity for particular optic flow stimuli,
      and possess characteristics which make them suitable neuronal participants in
      self-movement perception.

PMID- 9187284
TI  - Regenerating ganglion cell axons in the adult rat establish retinofugal
      topography and restore visual function.
AB  - The mechanisms of neuronal network response to axotomy are poorly understood. In
      one of the favoured models used to study the fate of injured neurons in the adult
      rat visual system, appreciable numbers of retinal neurons survive optic nerve
      injury under conditions of microglia-targeted neuroprotection. Rescued neurons
      can regenerate their axons and become target-dependently stabilised after
      reconnection with their natural visual centres by means of a peripheral nerve
      graft, which, in addition to guidance, actively supports axonal growth. The
      mechanisms that control regenerative axonal growth and resynaptogenesis include
      coordinated cell-cell interactions between growing neurites and target cells in
      order to establish a meaningful reconnectivity. Here the function of the
      regenerating visual circuitry was first studied by monitoring the ability of
      animals to discriminate spatial patterns, and second by recording visual evoked
      cortical potentials (VEPs) in the same animals. These functions were correlated
      with neuroanatomical studies of the retinotopic organisation of regenerating
      axons. To achieve these goals, adult rats were behaviourally trained in a Y-maze
      to discriminate between vertical and horizontal stripes. Both optic nerves were
      transected, and the regenerating axons of one optic nerve were guided into the
      area of optic tract with a peripheral nerve graft according to the protocols of
      neuroprotection and simultaneous grafting, in order to enable large numbers of
      axons to reinnervate the major visual targets in the midbrain and thalamus.
      Postoperative testing of the animals showed a marked improvement of visual
      perception and behaviour. The VEPs of the same animals were measurable indicating
      a restoration of the visual circuitry including the ascending corticopedal
      connections. Neuroanatomical assessment of the fibre topography within the graft
      and the area of termination revealed a rough topographic organisation that may
      account for restoration of the function. These results suggest that interrupted
      central pathways can be functionally reconnected by providing a neuroprotective
      environment in combination with peripheral nerve grafts to bypass lesions.

PMID- 9187285
TI  - Inter- and intra-sensory modality matching in children with hand-eye co
      ordination problems.
AB  - Inter- and intra-sensory modality matching by 8-year-old children diagnosed as
      having hand-eye co-ordination problems (HECP) and by a control group of children
      without such problems were tested using a target-location and pointing task. The
      task required the children to locate target pins visually (seen target), with the
      hand (felt target) or in combination (felt and seen target), while pointing to
      the located target was always carried out without vision. The most striking
      finding, for both the control and the HECP children, was the superiority of
      performance when the target had to be located visually. When combined scores for
      both hands were analysed, the HECP children showed inferior performance to the
      control children in both inter- and intra-modal matching. Analyses of the scores
      achieved with the preferred and non-preferred hand separately, however,
      demonstrated that the differences between the HECP and the control children
      could, in the main, be attributed to lowered performances when the non-preferred
      hand was used for pointing to the target. When pointing with the preferred hand,
      the only significant difference between the groups was when the target was
      visually located, the control children showing superior performance. Pointing
      with the non-preferred hand gave rise to significant differences, in favour of
      the control children, when the target was located visually, with the hand or in
      combination. These findings suggest that earlier studies, using only the
      preferred hand or a combination of the scores of both hands, might need to be
      qualified. Putative neurological disorders in the HECP children are invoked to
      account for the poor performance with the non-preferred hand.

PMID- 9187286
TI  - Anticipatory locomotor adjustments for accommodating versus avoiding level
      changes in humans.
AB  - The control of locomotion has been studied from various perspectives related to
      the tasks of pattern generation, equilibrium control or adaptation to the
      environment. The last of these locomotor components has received comparably less
      attention, specifically pertaining to anticipatory adjustments. Continuing the
      work which has been conducted on both humans and cats, the present paper explores
      the nature of the differences in anticipatory locomotor adjustments for obstacle
      avoidance versus the accommodation to level changes. Six subjects walked in six
      different environments including no obstructions, a simple obstacle, two
      different level changes (a platform and stairs), and a combination of an obstacle
      with each respective level change. Full dynamic analyses allowed comparison of
      muscle torques as well as muscle power generated and absorbed at the lower limb
      joints across conditions. It was found that the previously shown robust lower
      limb reorganization characterized by a knee flexor generation strategy was upheld
      in all conditions when the obstacle was present. Pure level changes involved an
      augmentation of the ongoing hip strategy inherent in normal level walking. In the
      compound environment of obstructed level changes, subjects chose to combine an
      augmentation of hip flexor power with a reorganization to active knee flexion.
      The results are discussed from the point of view of general principles of
      mechanical coordination and the exploitation of intersegmental dynamics for foot
      transport.

PMID- 9187287
TI  - Repetitive firing and oscillatory activity of pyramidal-like bursting neurons in
      the rat subiculum.
AB  - Electrophysiological characterization of neurons within the rat subiculum was
      carried out with intracellular recordings in an in vitro slice preparation.
      Subicular neurons responded to threshold pulses of depolarizing current delivered
      at a resting membrane potential (RMP) of 45.7+/-5.8 mV (mean+/-SD, n=85) with an
      initial burst of three to five fast action potentials that rode on a depolarizing
      envelope and was terminated by an afterhyperpolarization (burst AHP) (duration
      113+/-35 ms; peak amplitude 2.7+/-0.6 mV, n=10). Tonic firing replaced the
      bursting mode at membrane potential less negative than -55 mV. Suprathreshold
      depolarizing pulses evoked at RMP both an initial burst and successive tonic
      firing. Intracellular staining with biocytin showed morphological features
      typical of pyramidal cells (n=8). The relationship between frequency of
      repetitive firing and injected current (f-I) revealed that the burst firing
      frequency (250-300 Hz) was only slightly influenced by the amount of injected
      current. By contrast, the f-I curve of the tonic firing phase depended upon
      current intensity: it displayed an initial segment that increased at first
      linearly and then turned into a plateau for both the early and the late inter
      spike intervals. The frequency of the tonic firing declined only slightly with
      time, thus suggesting a lack of adaptation. During tonic firing, each single
      action potential was followed by a fast AHP and a depolarizing afterpotential.
      Termination of repetitive firing was followed by an AHP (spike-train AHP;
      duration 223+/-101 ms, peak amplitude 5.6+/-2.4 mV, n=17). Fast spike-train and
      burst AHPs were reduced by bath application of the Ca2+-channel blockers Co2+ (2
      mM) and Cd2+ (1 mM) (n=8), thus suggesting the participation of Ca2+-dependent K+
      conductances in these AHPs. Subicular bursting neurons generated persistent,
      subthreshold voltage oscillations at 5.3+/-1 Hz (n=20) during steady
      depolarization positive to -60 mV; at values positive to -55 mV, the oscillatory
      activity could trigger clusters of single action potentials with a periodicity of
      0.9-2 Hz. Oscillations were not prevented by application of excitatory amino acid
      receptor and GABA(A) receptor antagonists (n=5), Ca2+-channel blockers (n=5), or
      Cs+ (3 mM; n=4), but were abolished by the Na+-channel blocker tetrodotoxin (1
      microM; n=6). Our findings demonstrate that pyramidal-like subicular neurons
      generate both bursting and non-adapting tonic firing, depending upon their
      membrane potential. These neurons also display oscillatory activity in the range
      of theta frequency that depends on the activation of a voltage-gated Na+
      conductance. These electrophysiological properties may play a role in the process
      of signals arising from the hippocampal formation before being funnelled towards
      other limbic structures.

PMID- 9187288
TI  - Calcium-dependent, sustained enhancement of excitability during washout of
      aconitine in rat hippocampal slices.
AB  - Extracellular recording of the stimulus-evoked population spike was performed in
      the CA1 area of rat hippocampal slices in order to investigate delayed effects of
      the plant alkaloids aconitine and veratridine. Veratridine (1 microM and 10
      microM) suppressed the orthodromic and antidromic population spike. After washout
      of the drug, only a partial recovery was obtained. Aconitine (1 microM) exerted
      the same inhibitory action as veratridine. However, after washout, the spike
      amplitude was enhanced compared with the control. This enhancement of the spike
      amplitude was dependent on the concentration of aconitine and was maintained
      during the observation period of at least 2 h. Lowering the Ca2+ concentration of
      the bathing medium from 2.5 mM to 1.25 mM during application of aconitine
      attenuated recovery and prevented the enhancement observed during washout of the
      drug. Application of aconitine in the presence of CdCl2 as well as in the
      presence of inhibitors of protein kinase C and Ca2+/calmodulin-dependent protein
      kinase II prevented the increase in spike amplitude during washout with standard
      artificial cerebrospinal fluid. In contrast, the N-methyl-D-aspartate (NMDA)
      receptor antagonists D-AP5 and MK-801 as well as the non-NMDA receptor antagonist
      6-cyano-7-nitroquinoxaline-2,3-dione were ineffective in abolishing the aconitine
      induced enhancement. These data support the conclusion that different modes of
      action are involved in the effects of aconitine but not veratridine. It is
      concluded that the aconitine-induced increase in neuronal activity is mediated by
      intracellular Ca2+-dependent mechanisms leading to an activation of Ca2+
      dependent protein kinases. This effect is independent of Ca2+ entrance through
      NMDA and non-NMDA receptors.

PMID- 9187289
TI  - Frequency peaks of tremor, muscle vibration and electromyographic activity at 10
      Hz, 20 Hz and 40 Hz during human finger muscle contraction may reflect
      rhythmicities of central neural firing.
AB  - The output from the central nervous system to muscles may be rhythmic in nature.
      Previous recordings investigating peripheral manifestations of such rhythmic
      activity are conflicting. This study attempts to resolve these conflicts by
      employing a novel arrangement to measure and correlate rhythms in tremor,
      electromyographic (EMG) activity and muscle vibration sounds during steady index
      finger abduction. An elastic attachment of the index finger to a strain gauge
      allowed a strong but relatively unfixed abducting contraction of the first dorsal
      interosseous (1DI). An accelerometer attached to the end of the finger recorded
      tremor, surface electrodes over 1DI recorded EMG signals and a heart-sounds
      monitor placed over 1DI recorded vibration. This arrangement enabled maintenance
      of a constant overall muscle contraction strength while still allowing
      measurement of the occurrence of tremulous movements of the finger. Ten normal
      subjects were studied with the index finger first extended at rest and then
      contracting 1DI to abduct the index finger against three different steady forces
      up to 50% of maximal voluntary contraction (MVC). Power spectral analysis of
      tremor, EMG activity and muscle vibration signals each revealed three frequency
      peaks occurring together at around 10 Hz, 20 Hz and 40 Hz. Coherence analysis
      showed that the same three peaks were present in the three signals. Phase
      analysis indicated a fixed time lag of tremor behind EMG of around 6.5 ms. This
      is compared with previous measurements of electromechanical delay. Other
      experiments indicated that the three peaks were of central nervous origin.
      Introducing mechanical perturbations or extra loading to the finger and making
      recordings under partial anaesthesia of the hand and forearm demonstrated
      preservation of all the peaks, suggesting that they did not originate from
      mechanical resonances or peripheral feedback loop resonances. It is concluded
      that, at least for a small hand muscle, there exist not one but a number of
      separate peak frequencies of oscillation during active contraction, and that
      these oscillations reflect synchronization of motor units at frequencies
      determined within the central nervous system. It is proposed that the multiple
      oscillations may be a means of frequency coding of motor commands.

PMID- 9187290
TI  - Human eye-head coordination in two dimensions under different sensorimotor
      conditions.
AB  - The coordination between eye and head movements during a rapid orienting gaze
      shift has been investigated mainly when subjects made horizontal movements
      towards visual targets with the eyes starting at the centre of the orbit. Under
      these conditions, it is difficult to identify the signals driving the two motor
      systems, because their initial motor errors are identical and equal to the
      coordinates of the sensory stimulus (i.e. retinal error). In this paper, we
      investigate head-free gaze saccades of human subjects towards visual as well as
      auditory stimuli presented in the two-dimensional frontal plane, under both
      aligned and unaligned initial fixation conditions. Although the basic patterns
      for eye and head movements were qualitatively comparable for both stimulus
      modalities, systematic differences were also obtained under aligned conditions,
      suggesting a task-dependent movement strategy. Auditory-evoked gaze shifts were
      endowed with smaller eye-head latency differences, consistently larger head
      movements and smaller concomitant ocular saccades than visually triggered
      movements. By testing gaze control for eccentric initial eye positions, we found
      that the head displacement vector was best related to the initial head motor
      error (target-re-head), rather than to the initial gaze error (target-re-eye),
      regardless of target modality. These findings suggest an independent control of
      the eye and head motor systems by commands in different frames of reference.
      However, we also observed a systematic influence of the oculomotor response on
      the properties of the evoked head movements, indicating a subtle coupling between
      the two systems. The results are discussed in view of current eye-head
      coordination models.

PMID- 9187291
TI  - Involvement of protein kinase C in responses of rat dorsal horn neurons to
      mechanical stimuli and periaqueductal gray descending inhibition.
AB  - The effects of a protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol-13
      acetate (TPA), on the activity and periaqueductal gray (PAG)-induced inhibition
      of rat dorsal horn neurons of the lumbar spinal cord were tested. A microdialysis
      fiber was placed through the dorsal horn for the purpose of local application of
      pharmacological agents. Extracellular single-unit recordings from dorsal horn
      neurons were made near the microdialysis fiber. TPA was tested on nociceptive
      dorsal horn cells. There was a significant increase in the background activity
      and responses to "brush", with no changes in responses to pressure and pinch
      stimuli. TPA also significantly blocked the PAG-induced inhibition of responses
      to brush, press, and pinch. These effects were eliminated by coadministration of
      the PKC inhibitor NPC-15437. The solvent, which contained dimethyl sulfoxide, was
      also tested for its effect on the responses to peripheral mechanical stimuli and
      PAG-induced inhibition of the dorsal horn neurons. There were no significant
      changes. This experiment suggests that activation of the PKC second messenger
      system might increase the activity of dorsal horn neurons and their responses to
      peripheral stimuli; in addition, the phorbol ester attenuated the PAG-induced
      descending inhibition of the dorsal horn neuron activity.

PMID- 9187292
TI  - Age-related changes in cerebral blood flow activation during a Card Sorting Test.
AB  - To determine the age-related changes in the neural processing involved in the
      Modified Card Sorting Test (MCST), we measured cerebral blood flow (CBF) during
      performance of the MCST and of the number-matching task in young and elderly
      subjects using positron emission tomography. Compared with that during the number
      matching task, CBF during the MCST was increased in the left dorsolateral
      prefrontal cortex (DLPFC), left inferior parietal lobule, and left striate and
      prestriate cortices in both age groups. However, CBF activation in these areas
      was significantly lower in the elderly subjects than the young subjects.
      Furthermore, CBF activation was reduced in the left DLPFC, right parahippocampal
      gyrus, and prestriate cortex in proportion to the increase in the number of
      perseverative errors with aging. These results suggest that the impaired MCST
      performance in elderly subjects may be due, in part, to dysfunction of the
      network involving certain cortical areas such as the prefrontal and
      parahippocampal cortices, although the essential neural circuits for MCST
      performance were still preserved even in the elderly subjects.

PMID- 9187293
TI  - Scopolamine increases prehensile force during object manipulation by reducing
      palmar sweating and decreasing skin friction.
AB  - The aim of this study was to determine whether relatively long-term changes in
      skin friction induced by a pharmacological blockade of sweat excretion would
      alter the grip forces applied to objects of a variety of different surface
      textures and frictions. Five men and three women were asked to lift the
      vertically mounted armature of a linear motor between the thumb and index finger
      and to hold it against an opposing force for 2 s. A 1.0-kHz tone indicated to the
      subject that the manipulandum had been correctly positioned between the upper and
      lower position limits. The linear motor generated a 2.5-N force tangential to the
      skin surface simulating an object weighing approximately 250 g. Three different
      polyamide plastic surfaces (either smooth or etched with 1.0 mm high Braille
      beads evenly spaced at 2- or 3-mm intervals) contacted the fingers in these
      experiments. Subjects lifted and held in a precision grip one of the three
      surfaces for blocks of ten consecutive trials, but the order of presentation of
      the three different textures was varied to offset the effect of expectancy. On a
      second block of ten trials the subjects were requested to release the object
      slowly to measure the ratio of the grip force normal to the grasped surface to
      the tangential load force at the moment of slip. This ratio or its inverse
      provided the coefficient of friction or the slip ratio for a particular subject
      and surface condition. Twelve hours prior to a second recording session all
      subjects placed transdermal patches of 1.5 mg scopolamine behind each ear to
      reduce palmar sweating by blocking the muscarinic receptors of exocrine sweat
      glands. The subjects were re-tested following procedures that were identical to
      the first session. Scopolamine significantly reduced the friction of the skin on
      the smooth and 2-mm beaded surfaces, but the friction of the 3-mm beaded texture
      was unaffected. Scopolamine also caused subjects to increase both the peak and
      static grip forces for all the textures including the 3-mm beaded surface,
      suggesting that for two of the three surfaces they were responding to the
      increased slipperiness of the skin due to reduced sweat production.

PMID- 9187294
TI  - Selection of spatial frame of reference and postural control variability.
AB  - The present paper addresses the question of the possible links between perceptive
      visual field dependence-independence and the visual contribution to postural
      control. In our differential approach, visual field dependent (FD) and
      independent (FI) subjects were selected on the basis of their score in the Rod
      and Frame Test (subjective vertical). The hypothesis that we have tested is that
      the FD subjects use mainly visual cues for estimating not only their subjective
      vertical but also their body orientation and stability. Moreover, we have
      postulated that these subjects use mainly dynamic visual cues to control their
      postural stability. In the postural test, the selected subjects were instructed
      to stand in the sharpened Romberg position in darkness and under normal or
      stroboscopic illumination, in front of either a vertical or a tilted frame.
      Lateral head and body orientation and stability were measured. We found that: (1)
      all subjects leaned slightly towards the tilted frame (postural frame effect),
      and this was obtained on the basis of the static visual cues alone; (2) FD
      subjects were less stable than FI subjects, and their stability required the use
      of dynamic visual cues, mainly extracted from the vertical frame. In FI subjects,
      static visual cues may act as a complementary regulation, enhancing stability
      even with a strobe tilted frame. We thus demonstrate that visual field dependence
      interacts with the visual contribution to postural control.

PMID- 9187295
TI  - Aging decreases rebound synaptic excitation produced by removal of NMDA receptor
      block in the striatum.
AB  - The influence of age on NMDA receptor-mediated excitatory postsynaptic potentials
      (EPSPs) was characterized in striatal in vitro brain slices using intracellular
      recording techniques. All slices were bathed in bicuculline methiodide (20
      microM) to isolate EPSPs from intrinsic inhibition and Mg2+ was omitted from the
      artificial cerebral spinal fluid to reduce voltage-dependent fluctuations of NMDA
      receptor-mediated EPSPs. The NMDA receptor-mediated component of the EPSP was
      determined by comparing EPSP areas before and after block of NMDA receptors with
      5-amino-phosphonovaleric acid (AP-5; 30 microM). No age difference was found in
      the percentage contribution of the NMDA receptor-mediated component of the EPSP,
      but an age difference was observed in the response to removal of AP-5. On
      average, washout of AP-5 produced a significant enhancement of the EPSP in young
      cells, while in aged cells the EPSP returned, on average, to the pre-AP-5 control
      level. These data demonstrate that NMDA receptors contribute equally to EPSPs at
      young and aged synapses and that age-related decreases in the number of NMDA
      receptors may be related to synapse loss. In addition, the response to removal of
      AP-5 suggests that functional properties of NMDA receptors may also be altered by
      aging.

PMID- 9187297
TI  - Inverse correlation between expression of phosphatidylethanolamine N
      methyltransferase-2 and growth rate of perinatal rat livers.
AB  - Our previous studies have implicated the liver-specific phosphatidylethanolamine
      N-methyltransferase-2 (PEMT2) in suppression of hepatocarcinoma proliferation
      (Cui et al. (1994) J. Biol. Chem. 269, 24531-24533). It was not known if this
      phenomenon in cell culture had relevance to liver growth and PEMT2 expression in
      an intact animal. Hence, we investigated the relationship between normal
      proliferation of liver and the expression of PEMT2 during the perinatal period of
      developing rats. PEMT2 protein was completely absent, and PEMT activity was very
      low, in prenatal livers in which liver growth is rapid. At birth, a decrease of
      liver growth coincided with the rapid appearance in liver of a high level of
      PEMT2 protein that was sustained throughout adult life. Northern blots revealed
      that the postnatal expression of PEMT2 correlated with the level of its mRNA.
      Immunohistochemical staining of liver sections showed a distinctive pattern of
      PEMT2 expression at birth. A high level of PEMT2 was expressed in defined
      extranuclear regions of hepatocytes from newborn rats whereas the protein was
      dispersed in the extranuclear areas in adult hepatocytes. The inverse correlation
      between the rate of liver growth and PEMT2 expression together with other results
      suggest that this enzyme, or its product, is involved in control of normal liver
      proliferation.

PMID- 9187296
TI  - Induction of hepatocyte proliferation after partial hepatectomy is accompanied by
      a markedly reduced expression of phosphatidylethanolamine N-methyltransferase-2.
AB  - Expression of phosphatidylethanolamine N-methyltransferase (PEMT)-2 in rat
      hepatoma cells caused an increase in the time for cell division from 18 to 50 h
      [Cui et al. (1994) J. Biol. Chem. 269, 24531-24533]. We investigated whether or
      not a similar inverse relationship might exist for liver proliferation in vivo.
      Thus, partial hepatectomized rats were used to investigate the expression of
      PEMT2 during liver regeneration. Enhanced biosynthesis of phosphatidylcholine
      after partial hepatectomy was due to increased activity and amount of
      CTP:phosphocholine cytidylyltransferase. On the other hand the total activity of
      PEMT was markedly decreased during the first days of rat liver regeneration.
      Maximal decrease of total PEMT activity (45%) and loss of PEMT2 protein (90%)
      coincided with maximal DNA synthesis and CTP:phosphocholine cytidylyltransferase
      activity 24 h after partial hepatectomy in both male and female rats.
      Supplementing dietary choline in the diets of female rats shifted this pattern
      from 24 h to 36 h after partial hepatectomy, whereas the pattern in male rats was
      not affected. Northern blot studies showed that the amount of PEMT2 mRNA was
      decreased accordingly, suggesting regulation of the amount and activity of PEMT2
      at a pre-translational level. Thus, our data show a reciprocal regulation of
      CTP:phosphocholine cytidylyltransferase and PEMT2 at the level of gene expression
      in regenerating rat liver. These results implicate PEMT2 in the regulation of
      hepatocyte cell growth in a physiologically relevant model.

PMID- 9187298
TI  - Effect of dietary omega-3 eicosapentaenoic acid supplements on cholesteryl ester
      transfer from HDL in cholesterol-fed rabbits.
AB  - We investigated the reactivities of cholesteryl ester transfer protein (CETP) in
      Japanese white rabbits fed either a low-cholesterol diet containing 0.1%
      cholesterol (Control group) or a diet containing 0.1% cholesterol plus 17.5%
      omega-3 eicosapentaenoic acid (omega-3 20:5, EPA) of 4.5% (w/w) total lipid (EPA
      group) for 6 weeks. The plasma total and LDL cholesterol levels and aortic
      cholesterol content were all significantly higher in the EPA group than in the
      control group. The aortic cholesterol content significantly correlated with LDL
      cholesterol (r = 0.81). HDL cholesterol levels tended to be lower in the EPA
      group compared with control group, which was not statistically significant. The
      plasma VLDL cholesterol levels did not differ significantly between the groups.
      In addition, no significant differences were observed in the plasma CETP activity
      or lecithin:cholesterol acyltransferase (LCAT) activity between the groups.
      However, the cholesteryl ester (CE) mass transfer from fractionated HDL in the
      EPA group to excess VLDL and/or LDL as acceptors by purified CETP increased
      significantly compared with the control group, even if the acceptors were
      fractionated from either the EPA or the control group. Fatty acid analyses of CE
      showed that the omega-3 18:3, 20:4 or omega-3 20:5 fatty acid acyl groups in CE
      of HDL were significantly more transferred to apo B-containing lipoproteins
      compared with the 14:0,16:0, 18:0, 18:1 or 18:2 fatty acid acyl groups in CE of
      HDL during the incubation period. The amount of CE in HDL containing omega-3 18:3
      and omega-3 20:5 fatty acid acyl groups was greater, while the amount of CE
      containing 18:2 fatty acid acyl groups was smaller in the EPA group than in the
      control group. These results show that although CETP itself did not change, the
      transfer of CE in HDL to apo B-containing lipoproteins by CETP increased in the
      rabbits fed a diet containing EPA as the HDL is modified by the diet, which may
      partly explain why atherogenicity was thus found to progress in the rabbits fed a
      cholesterol plus EPA diet.

PMID- 9187299
TI  - Nucleotide sequence of human alkyl-dihydroxyacetonephosphate synthase cDNA
      reveals the presence of a peroxisomal targeting signal 2.
AB  - Two overlapping clones were isolated from a human liver cDNA library in lambda
      gt11 that coded for human alkyl-dihydroxyacetonephosphate synthase using guinea
      pig and PCR-derived human cDNA probes. The open reading frame encodes a protein
      of 658 amino acids that shows a homology of 92% with the guinea pig homolog and a
      similarity of 98%. The peroxisomal targeting signal 2 that was recently
      identified in the presequence of the guinea pig enzyme appeared to be completely
      preserved in the human enzyme. Supportive confirmation for parts of the sequence
      of the mature protein was obtained from the Expressed Sequence Tags database of
      the National Center for Biotechnology Information. This database contained nine
      cDNA sequences, derived from seven independent clones, that correspond exactly to
      parts of the cDNA of human alkyl-dihydroxyacetonephosphate synthase. One of these
      clones most likely represents a not fully processed RNA with a putative intron
      containing an Alu sequence. An unexpected homology with D-lactate dehydrogenase
      (cytochrome C) precursor from Saccharomyces cerevisiae and with glycolate oxidase
      subunit D from Escherichia coli was also revealed.

PMID- 9187300
TI  - Tumour growth modifies intravascular polyamine transport by plasma lipoproteins
      in the mouse.
AB  - Polyamines are polycationic compounds which are implicated in cell division and
      tumor growth. We have evaluated the potential role of plasma lipoproteins in the
      transport of major polyamines, spermine, spermidine and putrescine, and the
      effect of tumor growth on such transport. Plasmas of healthy male BL6/DBA2 mice
      and of mice bearing Lewis lung carcinoma (3LL) were fractionated by isopycnic
      density gradient ultracentrifugation, and polyamine content determined in
      lipoprotein fractions. Spermidine was the most abundant polyamine in the
      lipoproteins of both control and tumor-bearing mice and was principally
      associated with HDL (d: 1.046-1.136 g/ml); approx. 40% of total plasma polyamines
      was lipoprotein-associated in control mice and 60% in cancerous mice. Only minor
      amounts were transported by LDL (< 10% of total lipoprotein-associated
      polyamines), while VLDL were devoid of these substances. Marked elevations of
      circulating levels of LDL were found in 3LL grafted mice: in these particles
      however, the contents of spermidine and spermine were significantly reduced. A
      preferential uptake of polyamines by red blood cells could in part explain this
      marked reduction of LDL polyamine content, but the consequence of this reduction
      on the net electrical charge and biochemical function of LDL remains unknown.
      Elevations of plasma LDL and HDL levels in 3LL-grafted mice underlie the finding
      that only minor modification was detected in the putrescine content of these
      particles. However, it is evident that elevated total amounts of putrescine were
      present in the plasma of such animals. Finally, the density profile of polyamines
      was modified in cancerous mice in which a shift to transport in lighter apo.AI
      containing HDL particles was observed for spermidine; an even more marked shift
      was found for spermine. In conclusion, our data demonstrate that HDL particles
      constitute the major plasma vehicle for polyamine transport in both control and
      in tumor-bearing mice.

PMID- 9187301
TI  - Fatty alcohol synthesis accompanied with chain elongation in liver peroxisomes.
AB  - We have reported that the fatty alcohol destined to form the 1-alkenyl group of
      plasmalogen is synthesized as a nascent fatty alcohol within peroxisomes, from
      acetyl-CoA supplied by beta-oxidation. The present experiment was designed to
      confirm this peroxisomal fatty alcohol synthesis by using [1-14C]acetyl-CoA. Rats
      were fed for 2 weeks on chow containing 0.25% clofibrate, as a peroxisome
      proliferator. Peroxisomes were prepared from the rat liver to more than 85%
      purity, and incubated with [1-14C]acetyl-CoA in order to investigate suitable
      conditions for fatty alcohol biosynthesis. Dodecanoyl-CoA was the most suitable
      primer, and the reaction required NADH and/or NADPH as a reducing factor; NAD+ or
      NADP+ greatly inhibited the reaction, even if a significant amount of the reduced
      form still remained. The reaction proceeded linearly with respect to peroxisomal
      protein concentration and incubation time. Under the optimum conditions for fatty
      alcohol synthesis, 1 mg of peroxisomal protein could produce approx. 0.7 nmol of
      fatty alcohol per hour, and the main product was hexadecanol.

PMID- 9187302
TI  - HDL3-signalling in HepG2 cells involves glycosyl-phosphatidylinositol-anchored
      proteins.
AB  - In [3H]phosphatidylcholine (PC) prelabelled HepG2 cells, HDL3 stimulates a
      biphasic increase in 1.2-diacylglycerol (DAG). The early phase is mediated in
      part by a phospholipase C which is inhibited by 10 microM D 609, RHC-80267 or U
      73122 and less by 100 microM propranolol. A phospholipase D is more likely
      involved in the late phase, as the DAG peak lags behind phosphatidic acid rise
      and is blocked by 100 microM propranolol. Cellular preincubation with 200
      microg/ml antibodies against the inositolphosphoglycan (IPG) moiety of the GPI
      anchor (Ab(IPG)), or depletion in GPI-anchored proteins by cellular pretreatment
      with 0.5 U/ml PI-PLC, 1 mM insulin and 2 HU/ml streptolysin-O, or depletion in
      membrane cholesterol content by filipin (5 microg/ml), digitonin (5 microg/ml)
      and cholesterol oxidase (0.5 U/ml) decreases the HDL3-signal, suggesting the
      involvement of a lipolytic cleavage of GPI-anchored proteins. Inhibition of
      proteases by 1 mM leupeptin/PMSF improves the response time to HDL3, with a DAG
      peak at 2-3 min. In the presence of protease-inhibitors, HDL3 releases in the
      culture medium several proteins with a residual IPG that binds Ab(IPG) after SDS
      PAGE analysis and immunoblotting. HDL3-signalling pathways comprise tyrosine
      kinases, as preincubation with 100 microg/ml genistein or tyrphostin inhibits the
      HDL3-signal. HDL3 activates PC hydrolysis through a multistep pathway involving
      the cleavage of GPI-anchored proteins.

PMID- 9187303
TI  - Diffusible melanin-related metabolites are potent inhibitors of lipid
      peroxidation.
AB  - Although it has long been known that epidermal melanocytes produce and excrete a
      number of melanin-related metabolites, including 5.6-dihydroxyindole (DHI), 5,6
      dihydroxyindole-2-carboxylic acid (DHICA), and 5-S-cysteinyldopa (CD), the
      possible functional significance of these compounds has been so far largely
      overlooked. We report now evidence that DHI, DHICA and CD exert potent inhibitory
      effects in different in vitro models of lipid peroxidation. The compounds, at 100
      microM concentration, substantially decreased malondialdehyde (MDA) formation by
      lipid peroxidation in rat brain cortex homogenates. At 1.2 microM concentration,
      DHI proved as effective as alpha-tocopherol (alpha-T), one of the most potent
      endogenous antioxidants, in suppressing azo-induced peroxidation of linoleic acid
      in phosphate buffer (pH 7.4), containing 0.10 M SDS, whereas CD and DHICA at the
      same concentration were less active. DHI, CD and DHICA (all in the range 25
      microM-0.5 mM) were also found to inhibit Fe (II)/EDTA-induced oxidation of 0.5
      mM arachidonic acid at pH 7.4, as well as MDA formation by iron-promoted
      degradation of 0.5 mM 15-hydroperoxy-5,8,11, 13-eicosatetraenoic acid (15-HPETE).
      In both cases the inhibitory effects were much greater than those of ascorbic
      acid and glutathione. These results point to melanin precursors as a novel class
      of biological antioxidants which may contribute to defense mechanisms against
      oxidative injury in human skin.

PMID- 9187304
TI  - Isolation of ceramide fractions from human stratum corneum lipid extracts by high
      performance liquid chromatography.
AB  - This report describes a procedure to isolate ceramides from human stratum corneum
      lipid extracts using preparative liquid chromatography (LC) and semi-preparative
      high-performance liquid chromatography (HPLC) methods, which is economical in
      construction and operation. The composition of isolated individual 'peaks' of
      separated ceramide fractions is reported. These peaks were quantified by scanning
      of the chromatographic plates stained after high performance thin-layer
      chromatography (HPTLC). The HPTLC was done by automated multiple development
      (AMD). The enrichment of the ceramides by liquid chromatography turned out to be
      necessary for their separation from more polar lipids of the human stratum
      corneum lipid extract. Only the evaporative light scattering detector gave a
      stable baseline, reproducible results and eliminated the 'solvent front' in which
      peaks of interest could coelute. Fluorescence measurements of extracted human
      stratum lipids indicated lipofuscin-like substances.

PMID- 9187305
TI  - Fatty acid binding proteins reduce 15-lipoxygenase-induced oxygenation of
      linoleic acid and arachidonic acid.
AB  - Free fatty acids in plasma and cells are mainly bound to membranes and proteins
      such as albumin and fatty acid binding proteins (FABP), which can regulate their
      biological activities and metabolic transformations. We have investigated the
      effect of FABP and albumin on the peroxidation of linoleic acid (18:2) and
      arachidonic acid (20:4) by 15-lipoxygenase (15-LO). Rabbit reticulocyte 15-LO
      produced a rapid conversion of [1-14C]18:2 to 13-hydroxyoctadecadienoic acid (13
      HODE) and [3H]20:4 to 15-hydroxyeicosatetraenoic acid (15-HETE). 13-HODE
      formation was reduced when intestinal FABP (I-FABP). liver FABP (L-FABP) or
      albumin was added. The relative ability of these proteins to reduce 15-LO induced
      formation of 13-HODE and 15-HETE was BSA > L-FABP > I-FABP. Smaller reductions in
      activity were observed with 20:4 as compared to 18:2. The IC50-values of I-FABP
      and L-FABP, using either 18:2 (3.4 microM) or 20:4 (3.4 microM), were 4.6 +/- 0.6
      and 1.9 +/- 0.2 microM, respectively, for reduction of 13-HODE and 6.8 +/- 0.3
      and 3.1 +/- 0.2 microM, respectively, for reduction of 15-HETE formation. The
      smaller 15-HETE reduction correlated with decreased binding of 20:4 to the FABP.
      Titration calorimetry also showed that the I-FABP IC50 for 18:2, 0.25 microM, was
      lower then for 20:4, 0.6 microM. Thus the reduction in fatty acid lipid
      peroxidation relates to the binding capacity of each FABP. We also demonstrated
      that 18:2 rapidly diffuses (flip-flops) across the phospholipid bilayer of small
      unilamellar vesicles (SUV) and measured partitioning of 18:2 between proteins and
      SUV by the pyranin fluorescence method [Kamp, F. and Hamilton, J.A. (1992) Proc.
      Natl. Acad. Sci. U.S.A. 89, 11367-11370]. Addition of proteins to SUV in buffer
      resulted in a complete desorption of 18:2 from SUV with a relative effect of BSA
      > L-FABP > I-FABP. This suggests that the relative effects of these proteins on
      18:2 peroxidation will not be altered by the presence of membranes. Our results
      indicate that FAPBs protect intracellular polyunsaturated fatty acids against
      peroxidation and, through differential binding of 18:2 and 20:4, they may
      modulate the availability of these polyunsaturated fatty acids to intracellular
      oxidative pathways.

PMID- 9187306
TI  - On the mechanism of lysophospholipase activity of secretory phospholipase A2 (EC
      3.1.1.4): deacylation of monoacylphosphoglycerides by intrinsic sn-1 specificity
      and pH-dependent acyl migration in combination with sn-2 specificity.
AB  - We show for the first time that secreted low-molecular weight phospholipase A2
      (EC 3.1.1.4) catalyzes the deacylation of monoacylphosphoglycerides directly from
      the sn-1 position, although at a very low rate: purified phospholipase A2 enzymes
      from bee venom, crotalus atrox venom, and porcine pancreas hydrolyze the sn-1
      ester bond in 1-palmitoyl-2-O-methyl-sn-glycero-3-phosphorylcholine. Hydrolytic
      rates with the corresponding isomer, 1-O-methyl-2-palmitoyl-sn-glycero-3
      phosphorylcholine, are about 3-4 orders of magnitude higher. The similarities in
      Ca2+ requirement and inactivation profiles suggest that deacylation, albeit with
      different rates, from both sn-1 and sn-2 positions is catalyzed by the same
      catalytic site of phospholipase A2. Furthermore, evidence is provided that
      phospholipase A2-catalyzed 1-acyl lysophospholipid deacylation is mediated by sn
      1-directed action, but above pH 7 acyl migration with subsequent enzyme-catalyzed
      hydrolytic cleavage from the sn-2 position contributes to the overall deacylation
      of monoacylphosphoglycerides, acyl migration becoming eventually the rate
      limiting factor.

PMID- 9187307
TI  - Glycerolipid metabolizing enzymes in rat ventricle and in cardiac myocytes.
AB  - 1. The properties and subcellular distribution of phosphatidate phosphohydrolase
      (PAP) were studied in rat heart. A Mg2(+)-activated activity (PAP1) which was
      inhibited by N-ethylmaleimide was found mainly in a 105,000 x g soluble fraction.
      Isolation of the membranes in a medium containing KCl increased the proportion of
      PAP1 that was associated. Translocation of PAP1 from these membranes occurred on
      subsequent incubation in a low-ionic strength medium from which KCI was omitted.
      Incubation of cardiac myocytes with palmitate promoted translocation of PAP
      activity to cellular membranes. A second activity which was insensitive to N
      ethylmaleimide (PAP2) was found in the 105,000 x g membrane fraction. PAP2 was
      inhibited by concentrations of Mg2+ known to occur in ischaemia. Specific
      activities of PAP1 and PAP2 in ventricle muscle homogenates were similar. The
      specific activity of PAP2 in homogenates of cardiac myocytes was only 42% of that
      in homogenates of ventricle muscle. 2. A glycerolphosphate acyltransferase (GPAT)
      activity with properties similar to the GPAT found in microsomes from liver or
      adipose tissue was enriched in the sarcoplasmic reticulum fraction from ventricle
      muscle. This GPAT had a significantly higher K(m) for glycerol 3-phosphate than
      the GPAT found in adipose tissue microsomes. The possible physiological
      significance of this 'high K(m)' GPAT in heart, particularly in ischaemia, is
      discussed. 3. Comparisons were made of the specific activities of fatty acyl-CoA
      synthetase, monoacylglycerolphosphate acyltransferase, diacylglycerol
      acyltransferase and the mitochondrial and microsomal forms of GPAT in homogenates
      from cardiac myocytes and ventricle muscle.

PMID- 9187308
TI  - Effect of substituting amino acids in extracellular disulfide loop on GABA rho1
      subunit function.
AB  - Common features of GABA receptor/channels include a large extracellular NH2
      terminal region that is the receptor domain, and four putative transmembrane
      segments that contribute to form the channel. A conserved Cys-Cys loop of the NH2
      terminal domain in GABA receptor/channels is essential for maintaining the
      receptor and channel function. It has been suggested by other investigators that
      alteration of amino acids between these two cystines may affect the channel open
      kinetics. To investigate the mechanism underlying ligand binding and channel
      open, we have substituted several amino acids in the Cys-Cys loop of the GABA
      rho1 subunit and for the first time demonstrated the effect of mutations in the
      Cys-Cys loop on the single-channel kinetics of the rho1 subunit. For example, a
      single substitution of Arg198 in the extracellular Cys-Cys loop with Ala or Lys
      significantly reduced both the maximal amplitude of the whole-cell current and
      the single-channel open probability (Po). Single channel kinetics of mutants
      revealed no long open state, without changes in the short open state. There was a
      shift of apparent half-activation concentration (EC50) between the control and
      mutants in response to GABA. Our data further suggest that the Cys-Cys loop in
      the GABA rho1 subunit plays an important role in the receptor/channel function.

PMID- 9187309
TI  - Distribution of inositol-1,4,5-trisphosphate and ryanodine receptors in rat
      neostriatum.
AB  - The distribution of the inositol-1,4,5-trisphosphate (IP3) and the cardiac form
      of the ryanodine receptor, two intracellular calcium channels, was examined in
      the rat neostriatum. Both IP3 and ryanodine receptor labeling occurred within
      striatal medium spiny cells but only ryanodine receptor labeling was present in
      choline acetyltransferase- and parvalbumin-positive interneurons. IP3 receptor
      labeling was observed within cell bodies, dendrites and spines of spiny striatal
      neurons, as seen at both the light and electron microscopic levels. Subcellular
      labeling for the ryanodine receptor was restricted to cell bodies and proximal
      dendrites when a polyclonal antibody raised against a peptide sequence from the
      dog cardiac ryanodine receptor was employed. More extensive dendritic labeling
      was seen using monoclonal antibody MA3-916, also raised against the canine
      cardiac ryanodine receptor. At the ultrastructural level, labeled dendritic
      spines were observed frequently with the monoclonal but not the polyclonal
      antibody. Ryanodine receptor labeling also was present within astrocytic
      processes surrounding blood vessels and within the neuropil, regardless of the
      antibody used. The results of these studies suggest that the ryanodine receptor
      plays a general role in intracellular calcium regulation within striatal cells
      while the IP3 receptor plays a specialized role within spiny neurons.

PMID- 9187310
TI  - Neural responses to bitter compounds in rats.
AB  - To determine whether the idiosyncratic distribution of transduction mechanisms
      for bitter tastants in rat taste receptor cells (TRCs) could be inferred from the
      neural activity they evoke, single neuron responses to ten bitter-tasting
      compounds were recorded from rat glossopharyngeal (n = 30) and chorda tympani (n
      = 22) neurons. Responses to several 'bitter' alkaloids were obtained: 10 mM
      quinine-HCl, 50 mM caffeine, and 1 mM each nicotine, yohimbine, and strychnine,
      plus a number of non-alkaloid bitter-tasting compounds: 0.1 M KCl, 0.01 M MgCl2,
      and 1 mM each phenylthiocarbamide (PTC), L-tyrosine, and denatonium benzoate. To
      obtain some distinctions with other stimuli NaCl (0.1 M), HCl (pH 2.0), and
      capsaicin (10 microM) were also tested. It was found that individual neurons in
      both glossopharyngeal and chorda tympani nerves differed in their relative
      sensitivities to the various bitter stimuli. To determine relationships among
      these stimuli, the differences in the evoked responses between each stimulus pair
      were summarized in a multi-dimensional scaling space. In these analyses neither
      nerve showed any obvious similarity between the placements of quinine and the
      other bitter stimuli. Such data suggest that first-order gustatory neurons can
      discriminate among the above bitter stimuli. For glossopharyngeal neurons, some
      similarity to quinine was found only for nicotine and denatonium, and for chorda
      tympani neurons, some similarity to quinine was found only for KCl and MgCl2. Of
      the bitter compounds tested, quinine evoked the greatest response from
      glossopharyngeal neurons. We propose this arises because quinine can activate
      TRCs by more transduction mechanisms than other bitter stimuli. The results from
      these studies were summarized in a qualitative model for the coding of bitter
      tastants where the variety of transduction mechanisms for bitters are distributed
      among various TRCs to account for the heterogeneous responses among the neurons.

PMID- 9187311
TI  - Changes in glutamate receptors, c-fos mRNA expression and activator protein-1 (AP
      1) DNA binding activity in the brain of phenobarbital-dependent and -withdrawn
      rats.
AB  - We studied changes in glutamate receptors, expression of immediate early genes,
      and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and 
      withdrawn rats to investigate the possible involvement of activation of glutamate
      receptors in PB withdrawal syndrome. PB-dependent rats were prepared by feeding
      drug-admixed food for 5 weeks. Autoradiographic analysis showed that binding of
      [3H(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin e (MK-801), an
      antagonist of N-methyl-D-aspartic acid (NMDA) receptors, increased significantly
      in the cerebral cortices of PB-dependent and 24-h-withdrawn rats. However, [3H]MK
      801 binding in the hippocampus and [3H]6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and [3H]kainic acid binding in the hippocampus and cerebral cortex were
      essentially unchanged in both groups. PB withdrawal seizures were followed by
      increased expression of c-fos mRNA in the hippocampus and cerebral cortex and of
      c-jun mRNA in the cerebral cortex. The induction of c-fos and c-jun mRNA was
      suppressed by administration of MK-801. Furthermore, PB withdrawal enhanced AP-1
      DNA binding activity in the brain. The present findings suggest functional
      enhancement of glutamatergic neurotransmission during the development of PB
      withdrawal syndrome.

PMID- 9187312
TI  - Neurotransmission of the Bezold-Jarisch reflex in the nucleus tractus solitarii
      of sino-aortic deafferentated rats.
AB  - The Bezold-Jarisch (B-J) reflex was activated by serotonin (5-HT, i.v.) before
      and 10 min after bilateral microinjection of increasing doses of kynurenic acid,
      a non-selective antagonist of excitatory amino acid (EAA) receptors, into the
      commissural nucleus tractus solitarii (NTS) of sino-aortic deafferentated (SAD)
      and sham-operated (SO) unanesthetized rats. Increasing doses of kynurenic acid
      produced a dose-dependent blockade of the bradycardic and hypotensive responses
      to B-J reflex activation in both SO (from 0.1 to 10.0 nmol/100 nl) and SAD (from
      0.1 to 2.0 nmol/100 nl). Comparison of the effect of kynurenic acid on the
      hypotension and bradycardic dose-response curves showed a significant difference
      between SO and SAD rats, indicating that smaller doses of kynurenic acid are
      required in SAD rats than in SO rats to block the neurotransmission of the B-J
      reflex in the NTS. The data also showed that bilateral microinjection of
      kynurenic acid into the NTS at doses of 0.5 (131 +/- 7 vs. 115 +/- 8 mmHg) and
      2.0 nmol/100 nl (140 +/- 11 vs. 116 +/- 9 mmHg) produced an acute and significant
      increase in the basal mean arterial pressure of SAD rats similar to that observed
      with the same doses in SO rats, which was back to control values 5-10 min later.
      The increase in basal mean arterial pressure immediately after kynurenic acid
      microinjection into the NTS of SAD rats suggests that in the absence of the
      arterial baroreceptors, the B-J reflex plays an important role in the autonomic
      regulation of the circulation. The data also show different dose-response curves
      for hypotension and bradycardia in response to B-J reflex activation in SAD than
      in SO rats in the presence of increasing doses of kynurenic acid into the NTS,
      indicating that the neurotransmission of the B-J reflex in the NTS of SAD rats is
      more sensitive to the blockade of the EAA receptors than in SO rats.

PMID- 9187313
TI  - Ultrastructural localization of CD38 immunoreactivity in rat brain.
AB  - The subcellular localization of CD38 in the rat cerebral and cerebellar cortices
      was studied using immunoelectron microscopy. In the cerebral cortex,
      immunoreactivity was present in a subset of pyramidal neurons, and was
      distributed predominantly in the perikarya and dendrites. It was found in
      association with rough endoplasmic reticulum, ribosomes, small vesicles,
      mitochondria and the plasma membrane including the postsynaptic densities. In the
      cerebellum, labeling was observed in several types of neuron such as granule,
      Golgi, basket and Purkinje cells. In contrast to the cerebrum, immunoreactivity
      was accentuated in the perikarya or axon terminals, and the synaptic vesicles
      represented another organelle that was immunopositive for CD38. In both of these
      CNS regions, the nuclear envelope, particularly the outer membrane, showed
      constant labeling. Diffuse immunoreactivity was also present in the astrocytes
      from the perikarya to the processes including the perivascular glia limitans.
      Oligodendrocytes and microglia were immunonegative for CD38. The pattern of
      distribution of CD38 in the CNS is suggestive of multiple roles for this molecule
      at various functional sites in both neurons and astrocytes.

PMID- 9187314
TI  - Expression of endothelin receptors and nitric oxide synthase in the brain of
      stroke-prone spontaneously hypertensive rats with cerebral apoplexy.
AB  - Endothelin (ET) receptors, ET-1-like immunoreactivity and nitric oxide synthase
      (NOS) were examined in the brain of stroke-prone spontaneously hypertensive rats
      (SHRSPs) with cerebral apoplexy. Our receptor autoradiographic method with 125I
      ET-1 and unlabeled selective ligands for ET receptors revealed de novo
      expressions of ET(A) and ET(B) receptors in areas of neural lesions with
      cerebrovascular damage in SHRSPs. Immunohistochemical staining for ET-1 showed
      clear ET-1-like immunoreactivity in areas with highly expressed ET receptors.
      Histochemical studies on astrocytes and microglia suggested that these glial
      cells, aggregating in lesions, may carry ET receptors, ET-1-like
      immunoreactivity. Furthermore, NOS detected histochemically using an NADPH
      diaphorase staining method was rich on glial cells in damaged areas of the brain
      in SHRSPs with cerebral apoplexy. Our data suggest the pathophysiological
      significance of glial ET(A) and ET(B) receptors, ET-1 and NOS in neural lesions
      of SHRSPs.

PMID- 9187315
TI  - Decreased dorsal raphe nucleus neuronal activity in adult chloral hydrate
      anesthetized rats following neonatal clomipramine treatment: implications for
      endogenous depression.
AB  - Although the biological cause of endogenous depression is unknown, one commonly
      held hypothesis proposes that depression results, in part, from decreased central
      serotonin (5-HT) neurotransmission. Previous research found that clomipramine
      (CLI) treatment of neonatal rats produced, in adult rats, a variety of behavioral
      and physiological dysfunctions resembling those found in human endogenous
      depression. It was later reported that adult CLI-treated rats exhibited a
      decreased discharge of 5-HT neurons in the dorsal raphe nucleus (DRN) compared
      with control rats. This finding, however, was not replicated in subsequent
      studies that detected differences in DRN receptor function. Several factors were
      identified that may have contributed to the inability of the latter studies to
      detect CLI vs. control differences in DRN firing rates and interspike interval
      histograms (ISIH). Among these were the anesthetic used, the age at which the
      adult rats were tested, and the location of the recording electrode. The present
      study controlled these variables by using chloral hydrate anesthesia, testing
      'depressed' rats at both 2 and 3 months of age, and verifying electrode location
      using standard histological techniques. We found that DRN unit firing in
      'depressed' rats (0.417 +/- 0.071 spikes/s) was less than half that of 'non
      depressed' control rats (i.e. neonatal saline treatment 0.968 +/- 0.12 spikes/s).
      Additionally, ISIH's indicated that, in addition to the lower firing rate of 5-HT
      DRN neurons, adult CLI rats had an altered temporal discharge pattern of these
      neurons. Thus, the ISIH of 5-HT DRN neurons recorded from CLI rats was
      characterized by a flat distribution suggesting random temporal firing patterns.
      These results confirm previous findings of decreased DRN firing rates and flat
      ISIH's in 'depressed' rats and extend previous findings to younger rats of a
      different strain. The results thereby lend support to the hypothesis of a role
      for decreased central 5-HT as a substrate for the behavioral deficiencies
      observed in endogenous depression and suggest that these deficiencies may also
      result, in part, from a random, rather than orderly, temporal pattern of
      discharge in these neurons.

PMID- 9187317
TI  - Single doses of MK-801, a non-competitive antagonist of NMDA receptors, increase
      the number of 5-HT1A serotonin receptors in the rat brain.
AB  - In the present study, we investigated the impact of MK-801, a non-competitive
      NMDA receptor antagonist, on the density of serotonergic receptors of the 5-HT1A
      subtype and on the metabolism of serotonin in various regions of the rat brain
      containing terminals and cell bodies of serotonergic neurons. The binding of
      [3H]8-OH-DPAT to 5-HT1A serotonin receptors was increased after MK-801 (0.4
      mg/kg) as was shown by autoradiographic studies in the frontal, cingulate and
      part of enthorinal cortex, subregions of the hippocampus and raphe nuclei. The
      above receptor changes were observed at 2 h and, in some brain regions, at 24 h
      after MK-801. In saturation binding studies, an increase in the Bmax value in the
      rat hippocampus was found after MK-801 (0.4 mg/kg) while no changes being noted
      in the Kd value. MK-801 (0.4 mg/kg) increased the concentration of the serotonin
      metabolite 5-HIAA in the prefrontal cortex and hippocampus, respectively, at 2
      and 3 or 3 h after administration, being without effect on the level of
      serotonin. In the dorsal raphe nucleus, MK-801 (0.4 mg/kg) decreased the level of
      serotonin without affecting the level 5-HIAA (0.5 h after administration) or
      increased the level of 5-HIAA without altering the concentration of serotonin (3
      h after administration). It is concluded that single administration of MK-801 may
      alter the density of serotonergic 5-HT1A receptors and in consequence influence
      the function of the central nervous system associated with activation of 5-HT1A
      receptors.

PMID- 9187316
TI  - Adeno-associated virus (AAV) vector antisense gene transfer in vivo decreases
      GABA(A) alpha1 containing receptors and increases inferior collicular seizure
      sensitivity.
AB  - In the inferior colliculus, adeno-associated virus (AAV) vectors are capable of
      gene transfer and stable, long-term expression, but it remained to be shown if
      this in vivo gene transfer could alter focal seizure sensitivity in the inferior
      colliculus. Because GABA receptors directly modulate inferior collicular
      seizures, AAV vectors were constructed with a cytomegalovirus (CMV) promoter and
      a truncated, human GABA(A) alpha1 cDNA in both the sense and antisense
      orientations. Seven days after collicular microinjection of the sense vectors (1
      microl; 3 x 10(9) particles/microl), neurons exhibited GABA(A) alpha-like
      immunoreactivity in amounts far exceeding endogenous concentrations. Unilateral
      or bilateral sense vector infusion had no effect on inferior collicular seizure
      parameters or on [3H]zolpidem binding. In contrast, bilateral infusion of the
      antisense AAV-GABA(A) alpha1 vector (1 microl; 3 x 10(8) particles/microl) caused
      a 137% increase in the seizure duration. Moreover, unilateral antisense vector
      infusion produced a localized, 48% decrease in [3H]zolpidem binding. Thus, in the
      inferior colliculus, antisense AAV-CMV vectors can reduce a specific receptor
      subunit protein and change receptor function that directly influences in vivo
      seizure sensitivity.

PMID- 9187318
TI  - Circadian rhythm in the response to intracerebroventricular administration of 8
      OH-DPAT.
AB  - In a recent study, we observed circadian rhythms in the response to subcutaneous
      (s.c.) administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a
      serotonin (5-HT)1A receptor agonist, in rats. Although these results suggested a
      circadian rhythm in the function of the central 5-HT1A receptor, it was not
      possible to completely exclude drug disposition as the generating factor. The
      present study investigated circadian rhythms in the behavioral responses to
      intracerebroventricular administration of 8-OH-DPAT in rats. The results
      indicated the existence of circadian rhythms of a similar pattern to those
      observed in the forepaw treading and head weaving responses to s.c.
      administration of the drug. The flat body posture response observed following
      s.c. drug administration was not evident in the present study. These observations
      suggest that the central postsynaptic 5-HT1A receptor exhibits a circadian rhythm
      in its function.

PMID- 9187319
TI  - Effects of alcohol consumption on lateralized aggression in Anolis carolinensis.
AB  - Previous work has suggested that the lizard Anolis carolinensis, like many other
      reptiles, has a functionally split brain. Specifically, the left eye of this
      species projects primarily to the right hemisphere (and vice versa), there is no
      corpus callosum, and the physical placement of the eyes restricts their field(s)
      of vision to one region of hemispace. The current experiment used this
      preparation to examine the effect of alcohol administration and withdrawal on
      lateralized brain functioning during territorial aggression. Thirteen adult males
      were divided into control (CON) or alcohol (ETOH) groups. Baseline territorial
      aggression was assessed, following which ETOH subjects were then given twice
      daily solutions of 19% alcohol. After 19 days of ETOH consumption, territorial
      aggression was again assessed. Eye use during aggressive encounters was measured
      either following short periods (24 h) of alcohol withdrawal, or 90 m following
      alcohol consumption. Control subjects were found to have a predominance of left
      eye/right hemisphere-mediated aggressive responses, as has previously been
      reported. Alcohol withdrawn subjects were found to have a suppression of left
      eye/right hemisphere-mediated aggression. This reached statistical significance
      on several measures of aggression, including the number of dewlaps and headbob (P
      < 0.001) and the total number of aggressive responses (P = 0.001). Consumption of
      ETOH reversed this pattern and reinstated the normal pattern of left eye/right
      hemisphere dominance during aggression. Conversely, right eye/left hemisphere
      mediation of aggression was found to be increased, or not affected, during
      alcohol withdrawal, and to show no differences from CON following ETOH
      administration. Extrapolating from other recent findings in this species, these
      results suggest that the stress caused by ETOH withdrawal on the CNS may
      differentially effect the right hemisphere of the brain while having little
      effect on the left.

PMID- 9187320
TI  - Disinhibition of the hypothalamic paraventricular nucleus increases mean
      circulatory filling pressure in conscious rats.
AB  - Venous capacitance plays an important role in the control of cardiac output.
      However, the central nervous system sites and neurochemical signals involved in
      modulating venous function remain to be fully elucidated. The hypothalamic
      paraventricular nucleus (PVN) is an important site modulating autonomic outflow
      to the cardiovascular system. The present study tested the hypothesis that
      removal of tonic GABAergic tone in the PVN would increase peripheral venous tone.
      Mean circulatory filling pressure was used as an index of venous tone. Arterial
      pressure, venous pressure, heart rate, and mean circulatory filling pressure
      (MCFP) were monitored in conscious male Sprague Dawley rats. The rats were
      challenged with microinjections of bicuculline methiodide (BMI) (25 ng) or
      vehicle (artificial cerebrospinal fluid) into the PVN. In one group of rats, BMI
      injections were performed before and after ganglionic blockade with
      chlorisondamine hydrochloride (10 mg/kg) and atropine (0.4 mg/kg) given
      subcutaneously. In a second group, BMI injections were performed in
      chlorisondamine-treated rats whose blood pressure had been returned to control
      with an infusion of norepinephrine. Injection of bicuculline into the PVN
      increased MAP (14 +/- 2 to 18 +/- 2 mmHg) and HR (49 +/- 12 to 74 +/- 14 bpm).
      MCFP also increased significantly by 1.00 +/- 0.17 to 1.39 +/- 0.18 mmHg,
      indicating an increase in the driving pressure for venous return. Injection of
      the vehicle did not affect these variables. In both groups, ganglionic blockade
      significantly attenuated the bicuculline-induced increases in MAP, HR and MCFP.
      These data indicate that sympathetic drive from the PVN to the venous system is
      under tonic GABAergic control.

PMID- 9187321
TI  - Locus coeruleus activation by colon distention: role of corticotropin-releasing
      factor and excitatory amino acids.
AB  - The present study was designed to elucidate the neurotransmitters involved in
      activation of the noradrenergic nucleus, locus coeruleus, by distention of the
      distal colon. Locus coeruleus spontaneous discharge rate was recorded from
      halothane-anesthetized rats before, during and after distention of the colon
      produced by inflation of a balloon catheter with varying volumes of water. Locus
      coeruleus activation by colon distention was volume-dependent and reversible.
      Activation of cortical electroencephalographic activity was temporally correlated
      with locus coeruleus activation during colon distention and prolonged distention
      (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and
      cortical electroencephalographic activation. The corticotropin-releasing factor
      antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or
      microinfused into the locus coeruleus (10 ng) significantly attenuated locus
      coeruleus activation produced by lower, but not higher magnitudes of colon
      distention, implicating corticotropin-releasing factor afferents to the locus
      coeruleus in this response. Consistent with this, prior exposure to 30 min of
      footshock stress, which desensitizes locus coeruleus neurons to corticotropin
      releasing factor, produced a similar attenuation of locus coeruleus activation by
      low, but not high magnitudes of distention. Kynurenic acid, administered
      intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus
      activation by all magnitudes of colon distention. However, this excitatory amino
      acid antagonist was ineffective when administered directly into the locus
      coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of
      colon distention activate the locus coeruleus-noradrenergic system via
      corticotropin-releasing factor release within the locus coeruleus and that
      excitatory amino acid neurotransmission at a site distal to the locus coeruleus
      is necessary for this response. Activation of the locus coeruleus-noradrenergic
      system during colon distention may serve as a cognitive limb of the peripheral
      parasympathetic response. This activation may also play a role in disorders
      characterized by comorbidity of colonic and psychiatric symptoms, such as
      irritable bowel syndrome.

PMID- 9187322
TI  - Increased expression of M2 muscarinic receptor mRNA and binding sites in the
      rostral ventrolateral medulla of spontaneously hypertensive rats.
AB  - A significant body of evidence suggests that the development and maintenance of
      elevated blood pressure in the spontaneously hypertensive rat (SHR), a genetic
      model for essential hypertension, is due at least partly to a central hyper
      cholinergic state. For example, this strain responds with an exaggerated pressor
      response to pharmacological stimulation of central muscarinic receptors in
      certain brain regions compared to normotensive Wistar Kyoto rats (WKY). At least
      part of the enhanced response to central muscarinic receptor stimulation in SHR
      is due to the altered expression of post-synaptic receptors. In the present
      study, the reverse transcriptase-polymerase chain reaction and autoradiographic
      techniques were used to estimate the relative levels of mRNA and density of
      receptor binding sites for the five subtypes of muscarinic receptors within the
      rostral ventrolateral medulla (RVL) of SHR and WKY. Adult (12-week-old) SHR
      exhibited an increase in the levels of both M2 muscarinic mRNA, and M2 receptor
      binding sites in RVL compared to age-matched normotensive WKY. Similarly, 4-week
      old pre-hypertensive SHR exhibited increased levels of M2 mRNA in whole medulla
      oblongata, and an increase in the number of binding sites for M2 receptors in the
      RVL. Since the RVL is known to integrate tonic cholinergic sympathoexcitatory
      input, these results suggest that the increased expression of M2 muscarinic
      receptors in this region represents one neurochemical correlate for the
      maintenance of excessive central efferent sympathetic nervous activity in the
      SHR. Since the neurochemical change precedes the development of hypertension, the
      altered medullary M2 receptor expression may play a role as an initiating or
      predisposing factor for the development of hypertension in SHR.

PMID- 9187323
TI  - Metabolic and permeability changes caused by thiamine deficiency in immortalized
      rat brain microvessel endothelial cells.
AB  - The possible involvement of blood-brain barrier (BBB) breakdown in the
      pathogenesis of thiamine deficiency encephalopathy was investigated in RBE4
      cells, an immortalized rat brain endothelial cell line. The effects of thiamine
      deficiency produced by addition of pyrithiamine and by reduction of thiamine in
      the culture medium, on the metabolism and permeability of the RBE4 monolayer was
      examined. Pyrithiamine treatment in low thiamine medium (M199) for 7 days caused
      cytotoxic effects on RBE4 cells at all concentrations (10-50 microg/ml).
      Pyrithiamine caused a concentration- and time-dependent decrease in MTT reduction
      and a significant increase in glucose consumption and lactate production compared
      to controls. Pyrithiamine treatment for 3 days caused a significant decrease in
      MTT reduction at 50 microg/ml only. In contrast, increased glucose consumption
      and lactate production by the RBE4 cells was observed after treatment for 3 days
      with concentrations of 25 microg/ml pyrithiamine and above. The permeability of
      RBE4 cell monolayers to [14C]sucrose (Mw 342), but not FITC-dextran (Mw 4000) was
      significantly increased by treatment with pyrithiamine concentrations of 25
      microg/ml and above for 3 days. These effects were not accompanied by detectable
      changes in F-actin distribution or content, although F-actin content was
      significantly reduced by 7 days exposure to pyrithiamine. These results suggest
      that metabolic and permeability changes in thiamine-deficient RBE4 cells may be
      important early events in thiamine-deficiency encephalopathy. The relative role
      of the BBB in the pathogenesis of thiamine deficiency is discussed.

PMID- 9187324
TI  - The development of morphine tolerance and dependence in rats with chronic pain.
AB  - The development of tolerance and dependence to morphine injected onto the spinal
      cord was examined in a model of chronic pain following spinal cord injury in
      rats. Intrathecal morphine completely relieved the marked pain-like response of
      these rats to innocuous mechanical stimuli. The analgesic effect of morphine
      injected twice daily was, however, diminished within a few days. Tolerance to the
      antinociceptive effect of morphine assessed with the tail flick test also
      developed similarly in rats with chronic pain and in normal controls. Both groups
      exhibited similar signs of naloxone-precipitated withdrawal after 3 weeks of
      morphine treatment. The results suggest that the presence of chronic pain-like
      behavior did not prevent the development of morphine tolerance and dependence,
      even when morphine was used to treat the chronic pain itself.

PMID- 9187325
TI  - Rat's claustrum shows two main cortico-related zones.
AB  - Methods of retrograde axonal transport were employed to evaluate the topography
      and overlap of claustroneocortical connections in the rat. Fluorescent tracers
      Fast Blue (FB) and Diamidino Yellow (DY) were injected simultaneously in various
      combinations into the motor, somatosensory, auditory and visual cortical areas.
      Experiments showed that claustroneocortical projections are organized in two main
      cortico-related zones: sensorimotor and visuoauditory. The sensorimotor zone
      occupies the anterodorsal part whereas the visuoauditory occupies the
      posteroventral part of the claustrum. Between these two main zones only a scanty
      overlap was observed. In the sensorimotor zone a large overlap between neurons
      projecting to the motor and somatosensory cortical areas exists. The
      visuoauditory zone is characterized by a full overlap of neuronal populations
      projecting to the visual and auditory areas.

PMID- 9187327
TI  - NMDA and non-NMDA receptor antagonists protect against excitotoxic injury in the
      rat spinal cord.
AB  - The neuroprotective properties of the N-methyl-D-aspartate (NMDA) antagonist
      dizocilpine (MK-801) and the non-NMDA antagonists 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo[f]quinoxaline (NBQX) and alpha-methyl-4-carboxyphenylglycine
      (MCPG) were evaluated against neuronal injury produced by the intraspinal
      injection of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA). Forty-nine animals were divided into eight groups in order to evaluate
      the effects of different drug combinations: (a) NMDA; (b) NMDA + MCPG; (c) NMDA +
      NBQX; (d) NMDA + MK-801; (e) AMPA; (f) AMPA + MCPG; (g) AMPA + MK-801; and (h)
      AMPA + NBQX. Drugs were microinjected into spinal segments T12-L3 through a
      micropipette attached to a Hamilton microliter syringe. Spinal cords were
      evaluated after a survival period of 48 h at which time NMDA and AMPA were found
      to produce morphological changes over the concentration ranges of 125-500 mM and
      75-500 microM, respectively. Neuronal loss following injections of NMDA + MK-801
      or AMPA + NBQX was significantly less than that following injections of NMDA or
      AMPA alone. By contrast, neuronal loss following co-injections of NMDA or AMPA
      with inappropriate antagonists, i.e., NMDA + NBQX/MCPG or AMPA + MCPG/MK-801, was
      not significantly different from that produced by NMDA or AMPA. The results
      suggest that elevations in spinal levels of glutamate followed by prolonged
      activation of NMDA and AMPA receptor subtypes initiate an excitotoxic cascade
      resulting in neuronal injury. Blockade of NMDA and AMPA effects by MK-801 and
      NBQX respectively confirms the well documented neuroprotective effects of these
      drugs and lends support to the potential importance of NMDA and especially AMPA
      receptor antagonists as therapeutic agents in the treatment of acute spinal cord
      injury.

PMID- 9187326
TI  - Opposite modulatory effects of ovarian hormones on rat brain dopamine and
      serotonin transporters.
AB  - The present study was designed to investigate the modulatory effect of gonadal
      steroids on brain dopamine (DA) and serotonin (5-HT) presynaptic transporters in
      female and male rats. Female and male rats were castrated and treated with either
      vehicle or gonadal hormones. The pharmacodynamic characteristics of the DA and 5
      HT transporters were analyzed by [3H]BTCP and [3H]imipramine binding
      respectively. Ovariectomy (OVX) resulted in an upregulation of the striatal DA
      transporter and this alteration was prevented by estradiol (E2) or E2 +
      progesterone (P) treatment but not by P alone. In contrast to the DA transporter,
      the hypothalamic 5-HT transporter was down-regulated by OVX in female rats and
      this decrease was reversed by the administration of E2, P or their combination.
      The striatal DA transporter and the hypothalamic 5-HT transporter in male rat
      were not affected by orchidectomy or by administration of testicular hormone. Our
      findings indicate that ovarian, but not testicular, steroid hormones may play an
      important role in the regulation of brain DA and 5-HT transporters. It appears
      that ovarian hormones modulate rat brain 5-HT and DA transporters in opposite
      directions. These interactions between ovarian steroids and presynaptic
      transporters may be relevant to DA- and 5-HT-related neuropsychiatric disorders.

PMID- 9187328
TI  - Saccadic eye movements, even in darkness, generate event-related potentials
      recorded in medial sputum and medial temporal cortex.
AB  - Saccadic eye movements (saccades) in primates organize the visual information
      about the environment into a pulsatile course. Recent studies from our laboratory
      have found substantial single unit activity, of extra-retinal origin, in medial
      temporal and inferotemporal cortex with each saccade (even in the dark). In the
      current experiment we studied event-related potentials to spontaneous saccades
      from electrodes in medial temporal cortex as well as medial septum. Significant
      event-related potentials were recorded in both regions (again even in the dark).
      These data suggest that higher-level processing itself may synchronize with
      saccades.

PMID- 9187329
TI  - Galparan induces in vivo acetylcholine release in the frontal cortex.
AB  - The chimeric peptide galparan (galanin(1-13)-mastoparan) induced the in vivo
      release of acetylcholine in the frontal cortex of rats when injected
      intracerebroventricularly, i.c.v. The ACh-releasing effects of galparan are
      reversible, dose-dependent, and not exerted at galanin receptors or at sites
      where mastoparan acts. Pertussis toxin pretreatment (i.c.v.) of the rats for 96 h
      prior to injection of galparan or of mastoparan completely prevented the ACh
      releasing effects of both galparan and mastoparan. It appears that galparan acts
      at a novel site in the release of ACh in the cerebral cortex in vivo.

PMID- 9187330
TI  - Decreased cocaine- and lidocaine-induced seizure response by dextromethorphan and
      DNQX in rat.
AB  - The present study investigated the effect of dextromethorphan and 6,7
      dinitroquinoxaline-2,3-dione (DNQX) pre-treatment on the development of cocaine-
      and lidocaine-induced seizures. The dopaminergic action of cocaine was also
      studied. The NMDA antagonist dextromethorphan and the non-NMDA (AMPA/kainate)
      antagonist DNQX both significantly decreased the intensity of the seizure
      response to intravenous convulsant doses of cocaine and lidocaine individually
      (20 mg/kg) and in combination (5 mg/kg each). The incidence of seizures in rats
      receiving cocaine or lidocaine individually was significantly reduced by pre
      treatment with dextromethorphan but not DNQX. Haloperidol did not have an effect
      on the incidence or intensity of seizures induced by cocaine or lidocaine, alone
      or in combination. The results suggest that local anesthetic-induced convulsive
      seizures are mediated by excitatory glutamate transmission through both NMDA and
      non-NMDA receptor systems.

PMID- 9187331
TI  - A role for adenosine A2 receptors in the induction of long-term potentiation in
      the CA1 region of rat hippocampus.
AB  - Although reductions in neurotransmission have been reported in response to
      agonist-mediated adenosine A1 receptor activation, the implications of A2
      receptor activation on synaptic transmission have not been well explored. We
      examined the role adenosine A2 receptors play in the efficacy of
      neurotransmission between the Schaffer collateral-CA1 pathway in the rat
      transverse hippocampal slice. A2 receptor blockade in the presence of complete A1
      receptor inhibition led to a reversible reduction of the field excitatory post
      synaptic potential (EPSP) slope in response to low-frequency test pulses (0.033
      Hz) indicating that A2 receptors can enhance synaptic transmission. A2 receptor
      blockade by the A2 antagonist, DMPX (3,7-dimethyl-1-propargylxanthine) prevented
      the induction of tetanus-induced long-term potentiation (LTP) of the EPSP. In
      contrast, no such effect on LTP induction was observed during A1 receptor
      blockade. We also examined the effects of DMPX on the induction of LTP during
      continued A1 receptor blockade with CPT. Under this condition, LTP was
      significantly reduced when compared to LTP induced in the presence of CPT alone.
      A similar result was found using the highly polar A2 antagonist 8-SPT (8-(p
      sulfophenyl)theophylline) suggesting that the effects of DMPX on LTP were not due
      to a direct action on an intracellular intermediate. DMPX had no effect on LTP
      expression if applied 45 min following the tetanus indicating that A2 receptors
      play no significant role in the maintenance phase of LTP. Selective A2a receptor
      activation did not alter the field EPSP. Similarly, selective blockade of the A2a
      receptor did not interfere with tetanus-induced LTP. Increases in neuronal firing
      rates can result in elevations in the concentration of extracellular adenosine.
      Together, these results suggest that the A2 receptors may play an important role
      in the induction although not the maintenance of hippocampal LTP and that the
      effect is likely to be mediated by the A2b receptor.

PMID- 9187332
TI  - Thymus graft reverses morphological deficits in dorsolateral frontal cortex of
      congenitally athymic nude mice.
AB  - The present investigation offers a basis for demonstrating that the cerebral
      cortex can be directly accessed through the immune system. This project was
      undertaken to provide a necessary step in confirming that the localized,
      deficient area of the cerebral cortex in the congenitally athymic nude mouse is
      related to the thymus, a gland necessary for the development of T-cells and the
      regulation of the neuro-endocrine system. We report that thymus engraftment,
      confirmed by reconstitution of CD4 and CD8 T-cells, in 30-day-old congenitally
      athymic female mice reverses deficiencies in the frontal cortex by day 60. A
      concomitant increase in serum prolactin was observed in thymic-grafted nude mice,
      suggesting a role by which prolactin may produce the morphological changes
      observed in the cerebral cortex.

PMID- 9187333
TI  - BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons.
AB  - The effects of brain-derived neurotrophic factor (BDNF) on glutamate-induced
      cytotoxicity were examined using primary cultures of rat cortical neurons. BDNF
      induced TrkB tyrosine phosphorylation in rat cultured cortical neurons. The cell
      viability was significantly reduced when cultures were briefly exposed to
      glutamate and incubated with normal medium for 24 h. Glutamate cytotoxicity was
      prevented by MK-801, which is a non-competitive blocker of N-methyl-D-aspartate
      and N(omega)-nitro-L-arginine, which is a blocker of nitric oxide synthetase.
      Delayed neurotoxicity was also induced by ionomycin, a calcium ionophore, and
      nitric oxide (NO) donors such as S-nitrosocysteine (SNOC) and 3
      morpholinosydnonimine (SIN-1). Incubating cultures with BDNF for 10 min to 24 h
      protected cortical neurons against glutamate neurotoxicity. The protective
      effects of BDNF against glutamate cytotoxicity were dependent on both its
      concentrations and incubation time. BDNF also prevented the ionomycin-, SNOC-,
      and SIN-1 induced cytotoxicity. These results indicate that BDNF protects
      cultured cortical neurons from NMDA receptor-mediated glutamate neurotoxicity by
      reducing cytotoxic action of NO.

PMID- 9187334
TI  - Basic FGF attenuates amyloid beta-peptide-induced oxidative stress, mitochondrial
      dysfunction, and impairment of Na+/K+-ATPase activity in hippocampal neurons.
AB  - Basic fibroblast growth factor (bFGF) exhibits trophic activity for many
      populations of neurons in the brain, and can protect those neurons against
      excitotoxic, metabolic and oxidative insults. In Alzheimer's disease (AD),
      amyloid beta-peptide (A beta) fibrils accumulate in plaques which are associated
      with degenerating neurons. A beta can be neurotoxic by a mechanism that appears
      to involve induction of oxidative stress and disruption of calcium homeostasis.
      Plaques in AD brain contain high levels of bFGF suggesting a possible modulatory
      role for bFGF in the neurodegenerative process. We now report that bFGF can
      protect cultured hippocampal neurons against A beta25-35 toxicity by a mechanism
      that involves suppression of reactive oxygen species (ROS) accumulation and
      maintenance of Na+/K+-ATPase activity. A beta25-35 induced lipid peroxidation,
      accumulation of H2O2, mitochondrial ROS accumulation, and a decrease in
      mitochondrial transmembrane potential; each of these effects of A beta25-35 was
      abrogated in cultures pre-treated with bFGF. Na+/K+-ATPase activity was
      significantly reduced following exposure to A beta25-35 in control cultures, but
      not in cultures pre-treated with bFGF. bFGF did not protect neurons from death
      induced by ouabain (a specific inhibitor of the Na+/K+-ATPase) or 4
      hydroxynonenal (an aldehydic product of lipid peroxidation) consistent with a
      site of action of bFGF prior to induction of oxidative stress and impairment of
      ion-motive ATPases. By suppressing accumulation of oxyradicals, bFGF may slow A
      beta-induced neurodegenerative cascades.

PMID- 9187335
TI  - Distribution of ionotropic glutamate receptor subunit immunoreactivity in the
      suprachiasmatic nucleus and intergeniculate leaflet of the hamster.
AB  - Glutamate is thought to mediate the effects of light on the circadian pacemaker
      contained in the suprachiasmatic nucleus. Glutamate can reset this pacemaker both
      in vivo and in vitro while glutamate antagonists can reduce photically induced
      phase shifts in activity rhythms and c-fos expression in the suprachiasmatic
      nucleus. Most behavioural and gene expression experiments investigating circadian
      rhythms use hamsters, but the majority of the anatomical data on the presence and
      distribution of selected glutamate receptor subunits in the suprachiasmatic
      nucleus has been collected from rat. In the present study, we examined the
      distribution of ionotropic glutamate receptor subunits in the hamster
      suprachiasmatic nucleus using mono- and polyclonal antibodies directed against
      these subunits. In addition, we examined the distribution of immunostaining for
      these subunits in a second structure of the mammalian circadian system, the
      intergeniculate leaflet of the thalamus since it also is thought to receive
      glutamatergic input from the retina and is important in the entrainment of
      circadian rhythms. The results indicated that all of the subunits investigated
      (GluR1, GluR2/3, GluR4, GluR5/6/7, and NMDAR1) were present in the
      suprachiasmatic nucleus and that all but GluR4 were present in the
      intergeniculate leaflet. Each of the subunits investigated had a unique pattern
      of distribution and intensity of staining. The distribution of immunoreactivity
      for these subunits in the hamster suprachiasmatic nucleus and intergeniculate
      leaflet differed from that reported in the rat. The presence of these subunits in
      the suprachiasmatic nucleus and intergeniculate leaflet implies the presence of
      functional NMDA and non-NMDA receptors in these structures that may have a role
      in photic entrainment of the circadian pacemaker.

PMID- 9187336
TI  - A novel type of calcium channel sensitive to omega-agatoxin-TK in cultured rat
      cerebral cortical neurons.
AB  - We characterized the electrophysiological properties of calcium channels in
      cultured rat cerebral cortical neurons using omega-agatoxin-TK (omega-Aga-TK) by
      a patch-clamp technique. Two types of slowly inactivating calcium channels
      sensitive to omega-Aga-TK were detected. The first type showed high sensitivity
      to omega-Aga-TK and low recovery from the omega-Aga-TK-induced blockade during
      washout, corresponding to the P-type channel. The second type showed low
      sensitivity to omega-Aga-TK and high recovery, resembling the Q-type channel,
      although it was distinct from the Q-type in terms of slower inactivation
      kinetics. We designate this channel as Q(L)-type (long-lasting Q channel). The
      omega-Aga-TK-sensitive calcium channels involved in the glutamatergic synaptic
      transmission were also divided into two types based on the sensitivity to omega
      Aga-TK and reversibility of omega-Aga-TK-induced blockade. We conclude that the
      Q(L)-type is a novel type of channel, and that both P-type and Q(L)-type channels
      play a significant role in the cerebral cortical synaptic transmission.

PMID- 9187337
TI  - Neuroprotective sigma ligands attenuate NMDA and trans-ACPD-induced calcium
      signaling in rat primary neurons.
AB  - The effect of neuroprotective sigma ligands possessing a range of relative
      selectivity for sigma and phencyclidine (PCP) binding sites on N-methyl-D
      aspartate (NMDA) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans
      ACPD)-stimulated calcium flux was studied in 12-15-day-old primary cultures of
      rat cortical neurons. In approximately 80% of the neurons tested, NMDA (80
      microM) caused a sustained increase in intracellular calcium ([Ca2+]i). With the
      exception of R-(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ((+)-3
      PPP) (previously shown not to be neuroprotective) all of the sigma ligands
      studied significantly altered NMDA-induced calcium dynamics. The primary effect
      of dextromethorphan, (+)-pentazocine, (+)-cyclazocine, (+)-SKF10047,
      carbetapentane, 1,3-di(2-tolyl) guanidine (DTG), and haloperidol was to shift the
      NMDA response from a sustained, to either a biphasic or a transient, calcium
      event. In contrast to NMDA, the primary response observed in 62% of the neurons
      treated with trans-ACPD (100 microM) was a transient elevation in [Ca2+]i. Here,
      however, only the highly selective neuroprotective sigma ligands (i.e., those
      lacking substantial PCP binding affinity) significantly decreased the number of
      transient responses elicited by trans-ACPD whereas the PCP-related sigma ligands
      such as dextromethorphan, (+)-SKF10047 and (+)-cyclazocine were ineffective.
      Unexpectedly, (+)-3-PPP potentiated trans-ACPD activity. These results
      demonstrating attenuating effects of sigma ligands on NMDA-stimulated neuronal
      calcium responses agree with earlier studies using glutamate and KCl and identify
      a sigma receptor modulation of functional NMDA responsiveness. Furthermore, the
      ability of sigma ligands to attenuate NMDA-, trans-ACPD- and KCl-evoked neuronal
      calcium dynamics indicates that the receptor mechanisms mediating sigma
      neuroprotection comprise complex interactions involving ionotropic, metabotropic,
      and even voltage-gated calcium signaling processes.

PMID- 9187338
TI  - Distributions of single neurons related to body parts in the lateral striatum of
      the rat.
AB  - Single unit recordings in awake, unrestrained rats confirmed and extended
      previous findings regarding the functional organization of the lateral striatum.
      In individual electrode tracks, clusters of neurons related functionally to an
      individual body part were interspersed with clusters related to other body parts.
      The overlapping distributions of these neurons were arranged somatotopically in
      the dorsal-ventral dimension. The distribution of hind limb neurons was most
      dorsal and showed no overlap with the distribution of neurons related to oral
      sensorimotor activity. Oral representation was most ventral of all body parts and
      extended to the ventral boundary of the lateral striatum. Representations of
      other body parts overlapped with that of the hind limb dorsally but differed
      primarily in the degree to which they extended ventrally. Forelimb representation
      extended farther ventrally than that of the hind limb, but did not extend as far
      ventrally as that of the neck. Despite substantial overlap in the dorsal-to
      ventral order of hind limb-forelimb-neck-face representations, single neurons
      showed no evidence of overlap, or convergence, of body parts. These data provide
      a more complete description of the dorsal-ventral somatotopy in the lateral
      striatum of the rat, which as shown previously, extends throughout the medial
      lateral, and much of the anterior-posterior dimensions of the lateral striatum.

PMID- 9187339
TI  - Riluzole reduces brain lesions and improves neurological function in rats after a
      traumatic brain injury.
AB  - Riluzole (2-amino 6-trifluoromethoxy-benzothiazole) was studied in a rat model of
      traumatic brain injury (TBI) induced by a fluid percussion applied laterally to
      the right parietal cortex. Study I: vehicle or riluzole (4 or 8 mg/kg) was
      administered 15 min (i.v.), 6 h and 24 h (s.c.), after TBI. Brain lesions were
      quantified 1 week after insult. Riluzole significantly reduced the size of TBI
      induced lesions by approximately 44% with either dose regime (P < 0.05). Study
      II: vehicle or riluzole (8 mg/kg) was administered 15 min (i.v.), 6 h (i.p.) and
      then twice daily (i.p.) for 6 days, after injury. One, 2 and 3 weeks after TBI, a
      neurological examination was performed. Control injured rats had a significant
      neurological deficit at 1, 2 and 3 weeks (P < 0.001). Riluzole treatment did not
      modify the neurological status evaluated for the first 2 weeks after TBI. However
      at 3 weeks, riluzole significant improved the neurological function of injured
      rats (P < 0.05). These results suggest that riluzole may be beneficial in the
      clinical treatment of TBI. The protective action of riluzole may result from (i)
      stabilization of the inactivated state of voltage-dependent sodium channels, (ii)
      indirect action on the glutamatergic pathway, and/or (iii) indirect neurotrophic
      effect.

PMID- 9187340
TI  - Brain microsomal metabolism of phencyclidine in male and female rats.
AB  - These studies examined the microsomal brain metabolism of phencyclidine (PCP) in
      male and female Sprague-Dawley rats. Several monohydroxylated metabolites of PCP
      were detected including cis- and trans-1-(1-phenyl-4-hydroxycyclohexyl)piperidine
      (c-PPC and t-PPC) and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (PCHP). The in
      vitro formation of these metabolites required NADPH and was inhibited by carbon
      monoxide. c-PPC was formed in the male and female brain microsomes at rates of
      7.1 +/- 1.3 and 5.7 +/- 1.1 fmol/min per mg, respectively, while t-PPC was formed
      at rates of 16.2 +/- 3.3 and 16.5 +/- 4.2 fmol/min per mg. PCHP had the highest
      formation rate at 50.7 +/- 8.9 and 48.2 +/- 8.8 fmol/min per mg, respectively.
      Although previous studies with rat liver microsomes find higher levels of PCP
      metabolism in male rats and the formation of an irreversibly bound metabolite in
      male rats, the present study of brain metabolism found no sex differences in
      brain metabolism. The formation of PCP metabolites in male rat livers is at least
      partially mediated by the male-specific isozyme CYP2C11, and possibly CYP2D1.
      Nevertheless, the formation of the major brain metabolite, PCHP, was not
      inhibited by an anti-CYP2C11 or an anti-CYP2D6 antibody. However, PCHP formation
      was inhibited by drug inhibitors of CYP2D1-mediated metabolism, suggesting the
      involvement of a CYP2D isoform. These data indicate brain metabolism of PCP is
      significant, but unlike the liver it is not sexually dimorphic.

PMID- 9187341
TI  - Nicotinic control of tuberoinfundibular dopaminergic neuron activity and
      prolactin secretion: diurnal rhythm and involvement of endogenous opioidergic
      system.
AB  - The possible involvement of cholinergic and opioidergic neurons in the control of
      diurnal changes of tuberoinfundibular dopaminergic (TIDA) neuronal activity was
      reported. Adult Sprague-Dawley rats ovariectomized and treated with estrogen were
      used. All drugs were administered centrally through preimplanted
      intracerebroventricular cannula, and both TIDA neuronal activity and serum
      prolactin level were determined. Nicotine (10 ng/3 microl/rat) given at 10:00 h
      significantly inhibited TIDA neuronal activity from 5 to 30 min and stimulated
      serum PRL levels at 5 and 15 min. Co-administration of either mecamylamine (1
      microg) or naloxone (2.5 microg) prevented both nicotine's effects. A dose
      related (0.1-100 ng) effect of nicotine on TIDA neuronal activity and serum PRL
      level was also observed in the morning when TIDA neuronal activity is high and
      serum PRL level is low, but not in the afternoon when the former activity is low
      and the latter is high. When atropine (20 microg), naloxone (25 microg) or Nor
      BNI (20 microg) was given at 14:00 h all increased the lowered TIDA neuronal
      activity in the afternoon. When atropine was co-administered with either naloxone
      or Nor-BNI, however, no additive effect was observed. Submaximal doses of
      atropine (0.2 microg), mecamylamine (0.1 microg) or naloxone (0.25 microg) was
      also effective in stimulating the afternoon levels of TIDA neuronal activity and
      inhibiting serum PRL, and no additive effect was observed either. Moreover,
      simultaneous injection of morphine (15 microg) prevented atropine's effect in the
      afternoon. These results indicate that cholinergic neurons may act through
      activating the endogenous opioidergic neurons to exhibit an inhibitory effect on
      TIDA neuronal activity and a stimulatory one on prolactin secretion. A diurnal
      difference in its endogenous activity between morning and afternoon was also
      implicated.

PMID- 9187342
TI  - Axon sparing lesions of the medial preoptic area block female sexual behavior.
AB  - The role of the medial preoptic area (mPOA) in regulating female musk shrew
      sexual behavior was assessed with excitatory neurotoxin, N-methyl-D-aspartate
      (NMDA) lesions. Ovariectomized, testosterone-implanted females that received
      lesions in the mPOA were statistically less likely to show complete sex behavior
      as compared to controls. These data suggest that the mPOA plays an activational
      role in testosterone-induced female sexual behavior.

PMID- 9187343
TI  - Ethanol-induced c-Fos expression in rat lines selected for low and high alcohol
      consumption.
AB  - Selectively bred rat lines, developed to model genetic contributions to alcohol
      abuse, include the Indiana alcohol-preferring (P) and alcohol-nonpreferring (NP)
      lines, and the Alko-Alcohol (AA) and Alko-Nonalcohol (ANA) lines. Preferring and
      nonpreferring lines were compared in their response to intraperitoneal injection
      of either ethanol or isotonic saline using c-Fos expression as a marker of
      neuronal activity. Although line differences were noted in several brain regions,
      the principal finding was that alcohol-nonpreferring lines (NP and ANA) displayed
      greater c-Fos expression in the locus coeruleus (LC) relative to the alcohol
      preferring lines (P and AA) following injection of 3.0 g ethanol/kg. These data
      point to the LC as an area which may play a role in the differences in voluntary
      ethanol consumption between rat lines genetically bred for low and high ethanol
      preference.

PMID- 9187344
TI  - Heterogeneity in the neuropeptide Y-containing neurons of the rat arcuate
      nucleus: GABAergic and non-GABAergic subpopulations.
AB  - Neuropeptide Y, produced in the arcuate nucleus of the hypothalamus, plays a key
      role in the central regulation of anterior pituitary and appetitive functions.
      The pleiotropic nature of neuropeptide Y in these mechanisms indicates the
      existence of heterogeneity in the hypothalamic neuronal population producing
      neuropeptide Y. In this study, we report the coexistence of neuropeptide Y and
      the amino acid transmitter, gamma-aminobutyric acid (GABA), in neuronal perikarya
      of the arcuate nucleus. Fluorescent double immunolabeling for neuropeptide Y and
      glutamic acid decarboxylase was carried out on vibratome sections collected
      through the hypothalamic arcuate nuclei of animals that were pretreated with
      colchicine. It was found that about one third of the neuropeptide Y-producing
      arcuate nucleus perikarya co-expressed glutamic acid decarboxylase. This
      population of neuropeptide Y-containing GABAergic neurons were distributed
      longitudinally within the arcuate nucleus located predominantly in its
      dorsomedial aspects. These results show that there are at least two distinct
      populations of neuropeptide Y-producing neurons in the arcuate nucleus: a subset
      of neuropeptide Y and GABA-co-producing neurons located in the dorsomedial
      arcuate nucleus and a subset of non-GABAergic neuropeptide Y cells located in the
      ventral arcuate nucleus. This heterogeneity in the neuropeptide Y-producing
      perikarya of the hypothalamus may help explain adverse neuroendocrine and
      behavioral effects of arcuate nucleus neuropeptide Y.

PMID- 9187345
TI  - Effects of ethanol and nomifensine on NE clearance in the cerebellum of young and
      aged Fischer 344 rats.
AB  - Rapid chronoamperometric recordings coupled with local application of drugs by
      pressure ejection were used to investigate the effects of nomifensine and ethanol
      (EtOH) on exogenous norepinephrine (NE) clearance in the cerebellum of young (5
      month-old) and aged (24-26-month-old) male Fischer 344 rats. In the young rats,
      local nomifensine application prolonged exogenous NE clearance, indicating
      transporter mediated uptake inhibition. NE clearance was modestly but
      significantly prolonged in the aged rats as compared to the young rats,
      suggesting less efficient uptake. Consistent with this, there was little effect
      of nomifensine on NE clearance in the aged rats. In contrast to the effect of
      nomifensine, EtOH inhibited NE clearance in both young and aged rats. These data
      further support the hypothesis that one effect of EtOH in cerebellar NE systems
      is inhibition of NE uptake into NE-containing nerve terminals, and they also
      demonstrate that the effect of nomifensine on exogenous NE clearance in vivo in
      the cerebellum is altered by the aging process, while the effect of EtOH is not.

PMID- 9187346
TI  - The antidopaminergic action of S-20098 is mediated by benzodiazepine/GABA(A)
      receptors in the striatum.
AB  - The naphthalenic compound S-20098, which is a melatonergic agonist, inhibits
      [3H]diazepam binding in striatal membranes. S-20098 also inhibits apomorphine
      induced turning in 6-hydroxydopamine lesioned rats. This antidopaminergic effect
      is blocked by either intraperitoneal injection of the central-type benzodiazepine
      (BZ) antagonist, flumazenil, or intrastriatal injection of the GABA(A)
      antagonist, bicuculline. These findings indicate that S-20098 can activate
      central-type BZ receptors, and its antidopaminergic action, like that of
      melatonin, involves a GABAergic mechanism in the striatum.

PMID- 9187347
TI  - Viscero-somatic neurons in the primary somatosensory cortex (SI) of the squirrel
      monkey.
AB  - Thirty-eight neurons in the primary somatosensory cortex (SI) in alpha
      chloralose/Nembutal, or halothane (in N2O/O2) anesthetized squirrel monkeys were
      tested for responses to distention of the urinary bladder, the distal colon and
      the lower esophagus. Of the 38 SI neurons studied 13 were classified as
      visceroceptive. Eight of the 13 visceroceptive neurons responded to stimulation
      of a single viscus, the other five responded to two viscera. All SI neurons
      investigated had somatic low threshold type responses. Anesthesia was a critical
      factor, because 6 of 11 neurons responded to visceral stimulation only under a
      light halothane anesthetic level, and during moderate halothane anesthesia levels
      significantly more neurons exhibited visceral inputs than under alpha
      chloralose/Nembutal. The results suggest that the squirrel monkey SI is involved
      in processing of visceral information.

PMID- 9187348
TI  - Inhibition of NMDA-induced increase in brain temperature by N-omega-nitro-L
      arginine and indomethacin in rats.
AB  - Intracerebroventricular administration of N-methyl-D-aspartate (NMDA) caused an
      increase in brain temperature, which appeared rapidly and preceded that in rectal
      temperature, in urethane-anesthetized rats. The increase in brain temperature was
      divided into two phases, an early increase and a late increase.
      Intracerebroventricular indomethacin, a cyclooxygenase inhibitor, completely
      abolished the NMDA-induced late increase, but not the early increase, in brain
      temperature. On the other hand, intracerebroventricular N-omega-nitro-L-arginine,
      a potent inhibitor of nitric oxide synthase, strongly suppressed both the early
      and the late increases. These findings suggest that both nitric oxide and
      prostaglandins may be involved in the increase in brain temperature after NMDA
      receptor activation.

PMID- 9187349
TI  - Induction of NGFI-A gene expression in the rat suprachiasmatic nucleus by photic
      stimulation.
AB  - Photic induction of NGFI-A gene expression was investigated in the rat
      suprachiasmatic nucleus (SCN) using in situ hybridization histochemistry.
      Following light exposure for 30 min, NGFI-A mRNA appeared in the ventral portion
      of the rostral SCN, in the ventrolateral and in part of the dorsomedial portion
      at the middle level, and in the lateral portion of the caudal SCN. The
      distribution of NGFI-A mRNA was wider than that of c-fos mRNA which was confined
      to the ventrolateral portion at the middle level of the SCN. By double labeling
      in situ hybridization, approximately half of NGFI-A mRNA-positive cells in the
      SCN were shown to coexpress vasoactive intestinal peptide (VIP) mRNA, while 16%
      of cells positive for c-fos mRNA coexpressed VIP mRNA. These findings indicate
      that the broadness of NGFI-A mRNA and c-fos mRNA expression after photic
      stimulation are different. NGFI-A gene induced in these cells of the SCN
      including VIP neurons may be involved in circadian entrainment by light.

PMID- 9187350
TI  - Rolling in the clover: trefoil factor family (TFF)-domain peptides, cell
      migration and cancer.
AB  - Trefoil factor family (TFF)-domain peptides 1-3 are mucin-associated molecules,
      largely found in epithelia of gastrointestinal tissues. Structurally similar,
      resistant to enzymatic degradation, they are up-regulated around areas of
      epithelial damage such as ulcers. Transgenic expression or exogenous peptide
      ameliorates or prevents gastric mucosal damage due to indomethacin and some are
      rapidly up-regulated after cryogenic burns. A role in promoting cell migration is
      strongly suggested. Knockout mice lacking TFF1 or TFF3 show significant
      pathology, with the former developing gastric tumours. A recent Conference
      Philippe Laudat agreed upon a new nomenclature for these peptides.

PMID- 9187351
TI  - Influence of antibody binding on oxygen binding behavior of Panulirus interruptus
      hemocyanin.
AB  - Oxygen binding behavior of monomeric subunit a and the hexameric form of this
      subunit of hemocyanin of Panulirus interruptus is influenced by the binding of
      various monoclonal antibodies. These antibodies react with other surface parts of
      the subunit than its second domain in which the oxygen binding site is located.
      The influence of three monoclonal antibodies and their antigen binding fragments
      (Fab) has been investigated. Two antibodies increase the oxygen affinity of
      monomeric hemocyanin from that observed in its low affinity T-state, while the
      third has little influence on this property. Fab fragments abolish almost
      completely the cooperativity of oxygen binding by the hexameric hemocyanin
      molecule. The two antibodies which increase the oxygen affinity of the monomeric
      molecule stabilize high-affinity states of the hexameric molecule, while the
      third stabilizes the low-affinity state.

PMID- 9187352
TI  - Lipopolysaccharide interaction with hemolin, an insect member of the Ig
      superfamily.
AB  - This study is an attempt to reach some understanding of how insects recognize
      intruding microorganisms and foreign entities while executing an immune response.
      We used lipopolysaccharide (LPS) from Escherichia coli, bound to a radiolabeled
      iodinated crosslinker, to identify hemolymph proteins from the Hyalophora
      cecropia moth that have the capacity to bind LPS. High amounts of radioactivity
      were conferred to hemolin, an immunoglobulin and NCAM-related protein, the
      concentration of which increases in insect hemolymph upon bacterial infection. We
      could demonstrate a concentration-dependent binding of hemolin to LPS. In
      addition we could show that Lipid A can compete for this binding, whereas KDO has
      no effect, indicating that hemolin interacts specifically with the Lipid A moiety
      of LPS.

PMID- 9187353
TI  - Behaviour of nitric oxide synthase in rat cerebellar granule cells
      differentiating in culture.
AB  - The possible relation between nitric oxide synthase (NOS) activity and neural
      differentiation was investigated using primary cultures of rat cerebellar granule
      cells differentiating in culture. NOS activity was measured in the cytosolic and
      particulate fractions obtained from cell homogenate. In the experimental
      conditions used the optimal pH for NOS activity was about 6.4, the activity being
      about 3-fold higher than at pH 7.4. Cerebellar granule cell differentiation was
      associated with marked increases in NOS activity. In undifferentiated cells the
      enzyme was almost evenly distributed between the cytosolic and particulate
      fractions, during differentiation there was a 12-fold increase in activity in the
      cytosolic enzyme and a 3-fold increase in the particulate one. This indicates a
      marked preferential enrichment of the cytosolic enzyme during differentiation.
      Cerebellar granule cells produced and released NO in the culture medium; NO
      formation being markedly higher in differentiated cells (7-12 DIC) than in
      undifferentiated (2-3 DIC) ones. These data demonstrate a relationship between
      NOS expression and NO production and the differentiation of cerebellar granule
      cells, supporting the notion that NO may play a role in this process.

PMID- 9187354
TI  - Identification in the mu-opioid receptor of cysteine residues responsible for
      inactivation of ligand binding by thiol alkylating and reducing agents.
AB  - Inactivation by thiol reducing and alkylating agents of ligand binding to the
      human mu-opioid receptor was examined. Dithiothreitol reduced the number of
      [3H]diprenorphine binding sites. Replacement by seryl residues of either C142 or
      C219 in extracellular loops 1 and 2 of the mu receptor resulted in a complete
      loss of opioid binding. A disulfide bound linking C142 to C219 may thus be
      essential to maintain a functional conformation of the receptor. We also
      demonstrated that inactivation of ligand binding upon alkylation by N
      ethylmaleimide occurred at two sites. Alteration of the more sensitive (IC50 = 20
      microM) did not modify antagonists binding but decreased agonist affinity almost
      10-fold. Modification of the less reactive site (IC50 = 2 mM) decreased the
      number of both agonist and antagonist binding sites. The alkylation site of
      higher sensitivity to N-ethylmaleimide was shown by mutagenesis experiments to be
      constituted of both C81 and C332 in transmembrane domains 1 and 7 of the mu
      opioid receptor.

PMID- 9187355
TI  - Susceptibility of different subsets of immature thymocytes to apoptosis.
AB  - In the present study the susceptibility of different subsets of immature rat
      thymocytes to undergo apoptosis was examined. Unfractionated rat thymocytes were
      negatively enriched into immature double positive (CD4+ CD8+), immature single
      positive (CD4- CD8+ CD3-) and triple negative (CD4- CD8- CD3-) thymocytes. These
      enriched subsets of immature thymocytes were then exposed to various apoptotic
      stimuli such as dexamethasone, etoposide and thapsigargin which readily induced
      apoptosis in unfractionated rat thymocytes. We found that the double positive
      thymocytes and their precursor cells, i.e. the single positive immature
      thymocytes, were equally sensitive to apoptosis after treatment with the
      apoptotic stimuli. In sharp contrast, the early migrants or precursor-containing
      thymocytes which are triple negative have a lower spontaneous apoptosis rate and
      were relatively resistant to all the apoptotic stimuli. These findings showed a
      breakpoint in thymocyte sensitivity to apoptosis which occurs after the onset of
      CD8 expression, suggesting that susceptibility of thymocytes to apoptosis is
      developmentally regulated.

PMID- 9187356
TI  - Hydrogenosomes in the anaerobic fungus Neocallimastix frontalis have a double
      membrane but lack an associated organelle genome.
AB  - The presence of hydrogenosomes in phylogenetically distinct anaerobic eukaryotes
      implies that they have been acquired independently, and previously reported
      differences in ultrastructure among taxa have suggested that some hydrogenosomes
      have different origins. Of particular interest are reports that Neocallimastix
      frontalis hydrogenosomes resemble microbodies in possessing a single membrane, in
      contrast to those in ciliates and trichomonads which have two and thus resemble
      mitochondria. In this investigation we have clearly demonstrated that N.
      frontalis hydrogenosomes possess two, rather than one, closely apposed membranes
      and in some preparations cristae-like structures were observed. These
      observations have led us to reject the microbody hypothesis and provide some
      indirect support for a possible mitochondrion origin as proposed for other
      hydrogenosomes. N. frontalis hydrogenosomes were shown to lack an associated
      genome as previously demonstrated for trichomonad hydrogenosomes. This might be
      explained by assuming that a mitochondrial genome encoding proteins for aerobic
      function is no longer necessary for either organelle.

PMID- 9187357
TI  - MNDA dimerizes through a complex motif involving an N-terminal basic region.
AB  - Human myeloid cell nuclear differentiation antigen (MNDA) is a myelomonocytic
      lineage-specific protein that influences gene expression through interactions
      with other nuclear proteins and transcription factors. MNDA also self-associates
      and chemical cross-linking was used to demonstrate that MNDA forms a dimer. C
      terminal and internal deletion mutants were used to identify two regions in the N
      terminal half of MNDA essential for self-association. One region contains an
      imperfect leucine zipper and the second is highly enriched in basic residues. The
      sequences that are essential for dimerization are separated by a highly basic
      amphipathic alpha-helical region which was not required for dimerization.

PMID- 9187358
TI  - Purification and characterization of a fusion protein of plant acetohydroxy acid
      synthase and acetohydroxy acid isomeroreductase.
AB  - The nucleotide sequence coding for the Arabidopsis thaliana acetohydroxy acid
      synthase was genetically fused in frame with the nucleotide sequence coding for
      the Spinacia oleracea acetohydroxy acid isomeroreductase and expressed in
      Escherichia coli. This construction allowed the production of large amounts of
      soluble fusion protein. The pure chimeric enzyme exhibits high acetohydroxy acid
      synthase and acetohydroxy acid isomeroreductase specific activities. Fusion and
      native enzymes exhibit similar Km values for their substrates and for most
      cofactors. Furthermore, whereas native plant acetohydroxy acid synthase is highly
      unstable, the stability of this enzyme in the fusion has been increased. Thus,
      the chimeric enzyme appears to be a useful tool for the determination of kinetic
      and structural properties of plant acetohydroxy acid synthase.

PMID- 9187359
TI  - Inactive fatty acids are unable to flip-flop across the lipid bilayer.
AB  - Free fatty acids (FA) were found which did not acidify liposome interior. This is
      interpreted as their inability to rapidly flip-flop across the lipid bilayer.
      However, they were able to partition in lipids as detected directly using HPLC or
      from the shift of their equilibrium binding to acrylodated intestinal binding
      protein (ADIFAB) in the presence of vesicles. Various bipolar FA, such as 12
      hydroxylauric acid, dicarboxylic acids, or FA with benzene ring at the tail were
      found to be inactive in this way. A phenomenon of shielding, where an additional
      alkyl chain or non-polar group can restore the flip-flop activity, is described.

PMID- 9187361
TI  - A new transglutaminase-like from the ascidian Ciona intestinalis.
AB  - A cDNA clone encoding a transglutaminase (TGase) was isolated from a cDNA library
      prepared from the larval stage of Ciona intestinalis. The cDNA sequence has an
      open reading frame encoding a protein of 696 amino acids and is about 36%
      identical to 11 other TGase sequences. In addition, the critical residues thought
      to form the catalytic center are conserved. The Ciona TGase (CiTGase) has an
      extension of 39 amino acids in the NH2-terminal region similar to that reported
      for keratinocyte TGases. A phylogenetic analysis among other types of TGases
      demonstrated that CiTGase represents a new type of the enzyme.

PMID- 9187360
TI  - A structure-activity study of fatty acid interaction with mitochondrial
      uncoupling protein.
AB  - Fatty acid (FA) uniport via mitochondrial uncoupling protein (UcP) was detected
      fluorometrically with PBFI, potassium-binding benzofuran phthalate and SPQ, 6
      methoxy-N-(3-sulfopropyl)-quinolinium, indicating K+ and H+, respectively. The FA
      structural patterns required for FA flip-flop, UcP-mediated FA uniport,
      activation of UcP-mediated H+ transport in proteoliposomes, and inhibition of UcP
      mediated Cl- uniport by FA, were identical. Positive responses were found
      exclusively with FA which were able to flip-flop in a protonated form across the
      membrane and no responses were found with 'inactive' FA lacking the flip-flop
      ability. The findings support the existence of FA cycling mechanism.

PMID- 9187362
TI  - Ap3A and Ap4A are primers for oligoadenylate synthesis catalyzed by interferon
      inducible 2-5A synthetase.
AB  - The biological role of Ap3A synthesized in cells by tryptophanyl-tRNA synthetase
      (WRS) is unknown. Previously we have demonstrated that the cellular level of Ap3A
      significantly increases after interferon treatment. Here we show that the human
      46 kDa 2-5A synthetase efficiently utilizes Ap3A as a primer for oligoadenylate
      synthesis. The Km for Ap3A is several-fold lower than for Ap4A and 100-fold lower
      than for ATP. This implies that Ap3A might be a natural primer for the 2'
      adenylation reaction catalysed by 2-5A synthetase. Since WRS and 2-5A synthetase
      are both interferon-inducible proteins, a new link between two interferon
      dependent enzymes is established.

PMID- 9187363
TI  - Antibodies to rat soluble IL-6 receptor stimulate B9 hybridoma cell
      proliferation.
AB  - Interleukin-6 mediates its pleiotropic effects by interacting with its membrane
      bound receptor (gp80) or the soluble counterpart gp54, resulting in activation of
      a complex that includes the transducer protein gp130. We have generated a
      polyclonal antibody against the rat soluble IL-6 receptor (anti-rat sIL-6R) in
      rabbits. By Western blot analysis we show that purified anti-rat sIL-6R IgG
      antibody reacts specifically with recombinant rat sIL-6R generated from E. coli,
      baculovirus or adenovirus expression systems. Anti-rat sIL-6R inhibited IL-6
      induced acute phase protein synthesis in rat (H35) but not human (HepG2) hepatoma
      cells, and did not affect stimulation of those cells by Oncostatin-M. Conversely,
      on the mouse hybridoma B9 cell line, IgG anti-rat sIL-6R showed a dose-dependent
      stimulation of proliferation. Fab fragments of this antibody did not stimulate,
      but abrogated IL-6-mediated hepatoma cell stimulation and B9 cell proliferation.
      Gel shift analysis of STAT nuclear factors showed activation of STAT DNA binding
      in nuclei of B9 cells treated with IgG anti-rat sIL-6R, whereas in H35, NIH-3T3
      and M1 cells, only IL-6 could trigger a similar STAT activation. Our data suggest
      that mechanisms of IL-6 receptor activation and signalling in mouse B9 hybridoma
      cells show subtle but important differences from other IL-6-responsive cells.

PMID- 9187364
TI  - Cloning and functional expression of the murine homologue of proteinase 3:
      implications for the design of murine models of vasculitis.
AB  - Anti-neutrophil cytoplasmic autoantibodies recognizing conformational epitopes (c
      ANCA) of proteinase 3 (PR3) from azurophil granules are a diagnostic hallmark in
      Wegener's granulomatosis (WG). Because a functional PR3 homologue has not been
      identified in rodents, it is difficult to assess immunopathological responses in
      rats or mice immunized with patients' derived c-ANCA or human PR3. Here we report
      the full length cDNA cloning and functional expression of murine PR3 in HMC-1
      cells. Recombinant murine PR3 shows highly similar substrate specificities
      towards synthetic peptides and is inhibited by human alpha1-proteinase inhibitor
      like human PR3. However, neither human c-ANCA, rabbit sera nor mouse monoclonal
      antibodies to human PR3 recognize the murine homologue. Consequently, it is
      unlikely that disease observed in mice after immunization with c-ANCA or human
      PR3 is caused by pathogenic antibodies directed against mouse PR3. Recombinant
      human-mouse chimaeric variants will be a valuable new tool to localize the
      disease-specific immunodominant epitopes in human PR3.

PMID- 9187365
TI  - Mg2+ modulates membrane lipids in vascular smooth muscle: a link to
      atherogenesis.
AB  - Epidemiological studies associate low dietary magnesium intake with an increased
      incidence of ischemic heart disease and sudden cardiac death. We have used proton
      magnetic resonance (1H-NMR) techniques and Mg2+-selective electrodes to monitor
      changes in lipid extracts of aortic and cerebrovascular smooth muscle as
      extracellular ionized magnesium ion concentration ([Mg2+]o) is lowered. We have
      found that, within the pathophysiological range of Mg2+ concentrations, fatty
      acid chain length and double bond content are progressively reduced as [Mg2+]o is
      lowered. In contrast, the plasmalogen content is progressively increased. A
      concomitant decrease in fatty acid chain length and double bonds indicates
      oxidation of double bonds resulting in truncation of the fatty acids. A decrease
      in lipid oxidation in the presence of elevated Mg2+ could contribute to the
      apparent protective role of increased Mg2+ intake on vascular function in humans.

PMID- 9187366
TI  - Characterization of Aplysia carboxypeptidase E.
AB  - Carboxypeptidase E (CPE) is involved in the biosynthesis of peptide hormones and
      neurotransmitters. To determine whether a recently reported Aplysia californica
      cDNA encodes a CPE-like enzyme, this cDNA was expressed in the baculovirus
      system. The Aplysia CPE is optimal at pH 5.5-6.5 and is inhibited by chelating
      agents and by the sulfhydryl reagent p-chloromercuriphenyl sulfonate. The effect
      of divalent cations and active site-directed inhibitors on enzyme activity are
      generally similar for Aplysia and rat CPE. Western blot analysis using antisera
      to the N- and C-terminal regions of the Aplysia CPE show that the Aplysia CPE is
      present in atrial glands and ovotestis. This Aplysia CPE is purified on a p
      aminobenzoyl-Arg Sepharose affinity column under conditions that selectively
      purify rat CPE. Taken together, these results suggest that the previously cloned
      cDNA represents a CPE-like enzyme that is expressed in Aplysia tissue.

PMID- 9187367
TI  - A putative cytochrome c biogenesis gene in Synechocystis sp. PCC 6803.
AB  - A gene (orf334) with homology to chloroplast ycf5 (ccsA) was isolated from the
      cyanobacterium Synechocystis PCC 6803. The mRNA level of orf334 decreases in the
      dark and increases rapidly upon illumination. Transcription is initiated 69
      nucleotides upstream of the start site of translation. The deduced amino acid
      sequence of orf334 has limited identity with bacterial proteins involved in
      cytochrome c biogenesis. Sequence comparison indicates differing pathways of
      cytochrome c biogenesis in cyanobacteria/chloroplasts and Gram positive bacteria
      versus proteobacteria and mitochondria. Insertional inactivation of the orf334
      gene gave rise to a heterozygous mutant, i.e. complete absence of the orf334
      product seems to be lethal to the cell.

PMID- 9187368
TI  - Transmembrane topology of the Rieske Fe/S protein of the cytochrome b6/f complex
      from spinach chloroplasts.
AB  - The topology of the Rieske protein of the cytochrome b6/f complex in thylakoids
      from spinach chloroplasts was examined by protease protection experiments as well
      as polypeptide extraction assays using solutions of chaotropic salts or alkaline
      pH. While neither thermolysin nor trypsin cleave any of the Rieske protein when
      added to the stromal side of the thylakoid membrane, proteinase K is capable of
      removing approximately four residues from its NH2-terminus. The protein is
      resistant to membrane extraction by 0.1 M Na2CO3 or 2 M NaBr but is
      quantitatively released by 0.1 M NaOH. Treatment of thylakoids with 2 M NaSCN
      leads to extraction of variable amounts of the protein, depending on the presence
      or absence of sucrose in the medium which apparently stabilizes the cytochrome
      complex. From these results we conclude that the Rieske protein is an integral
      component of the cytochrome complex which spans the thylakoid membrane with a
      single hydrophobic segment and is anchored predominantly by electrostatic
      interactions.

PMID- 9187369
TI  - CKbeta8, a novel CC chemokine that predominantly acts on monocytes.
AB  - We have studied the biological properties of a new human CC chemokine, CKbeta8,
      consisting of 99 amino acids including six cysteines. CKbeta8 mRNA transcripts
      were induced in monocytes by IL-1beta and, to a lesser extent, by IFNgamma, and
      were detected in RNA extracted from normal human liver and gastrointestinal
      tract. CKbeta8 is chemotactic for monocytes, but is inactive on IL-2 conditioned
      T lymphocytes, eosinophils and neutrophils. Desensitization experiments indicate
      that CKbeta8 and MIP-1beta completely share receptors on monocytes and that the
      CKbeta8 receptor, which appears to differ from the known ones, is also recognized
      by MCP-1, MCP-2, MCP-3, MCP-4, MIP-1alpha and RANTES.

PMID- 9187370
TI  - Mitochondrial acyl carrier protein is involved in lipoic acid synthesis in
      Saccharomyces cerevisiae.
AB  - The yeast gene, ACP1, encoding the mitochondrial acyl carrier protein, was
      deleted by gene replacement. The resulting acp1-deficient mutants had only 5-10%
      of the wild-type lipoic acid content remaining, and exhibited a respiratory
      deficient phenotype. Upon meiosis, the lipoate deficiency co-segregated with the
      acp1 deletion. The role of ACP1 in long-chain fatty acid synthesis was studied in
      fast and fas2 null mutants completely lacking cytoplasmic fatty acid synthase.
      When grown on odd-chain (13:0 and 15:0) fatty acids, these cells showed less than
      1% of C-16 and C-18 acids in their total lipids. Mitochondrial ACP is therefore
      suggested to be involved with the biosynthesis of octanoate, a precursor to
      lipoic acid.

PMID- 9187371
TI  - A novel gene suppressed in the ventricle of carnitine-deficient juvenile visceral
      steatosis mice.
AB  - In order to clarify the pathogenesis and pathophysiology of cardiac hypertrophy
      in carnitine-deficient juvenile visceral steatosis (JVS) mice, we performed mRNA
      differential display analysis with total RNA extracted from the ventricles of
      control and JVS mice at 14 days of age. We identified four up-regulated genes,
      two known and two unknown, and a novel down-regulated gene. Northern blot
      analysis with a novel cDNA probe derived from the down-regulated gene fragment
      8A2 revealed three mRNA species of 1.1-, 1.3-, and 2.6-kb. The 1.1- and 1.3-kb
      mRNA species were found only in the heart, and the 2.6-kb species was found in
      the heart, kidney and brain, but not in skeletal muscle or liver. The 1.1- and
      1.3-kb species were down-regulated in the ventricles of JVS mice, but not in the
      auricles, and increased to the control level with carnitine treatment. We
      isolated cDNA clones from ventricle RNA, termed CDV-1 (carnitine deficiency
      associated gene expressed in ventricle) and from brain RNA, termed CDV-1R (CDV-1
      related gene) by 5'- and 3'-RACE analyses. The entire nucleotide sequence except
      the 5'-terminal 64 bp of CDV-1 cDNA was completely identical to the 992 bp
      sequence from the 3'-end of CDV-1R cDNA. The CDV-1 cDNA contained an open reading
      frame predicting a peptide of 107 amino acids, which composed the C-terminal
      portion of CDV-1R peptide consisting of 414 amino acids.

PMID- 9187372
TI  - DNA fragmentation is a feature of cystic fibrosis epithelial cells: a disease
      with inappropriate apoptosis?
AB  - Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR
      gene, which result in disrupted chloride secretions with inspissated mucous
      secretions by exocrine glands. Nick-end labelling was used to assess DNA
      fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two
      control lung tissues. In CF small intestine median 46% (range: 30-82) villus
      enterocytes show DNA fragmentation (vs. 3% (range: 1-7) in controls P < 0.001)
      and median 37.5% (range: 23-79) crypt enterocytes show Ki67 antigen (P < 0.001).
      In CF airways 57% (range: 54-70) of epithelial cells show DNA fragmentation.
      Inappropriate high DNA fragmentation is a feature of various CF epithelia. This
      could have great impact in understanding the mechanisms leading to disease.

PMID- 9187373
TI  - Cationic cholesterol with a hydroxyethylamino head group promotes significantly
      liposome-mediated gene transfection.
AB  - A novel cationic cholesterol derivative with a hydroxyethylamino head group,
      cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine (II), has been
      synthesized and used for liposome-mediated gene transfection. The cationic
      liposomes containing the derivative (II) facilitated greatly pSV2CAT gene
      transfection into mouse NIH3T3 and L929 cells in the absence of serum. The
      transfection efficiency was much higher than those by the cationic liposomes
      containing cationic derivatives with a dialkylamino head group (I, III or IV).
      Further, the efficiency by the cationic liposomes with the derivative (II) was
      not so much decreased in the presence of serum. This suggested that a novel
      cationic cholesterol derivative (II) should be very promising in liposome
      mediated gene transfection of plasmid and antisense DNA into target cells.

PMID- 9187374
TI  - The Aspergillus nidulans transcription factor AlcR forms a stable complex with
      its half-site DNA: a NMR study.
AB  - The Aspergillus nidulans transcription factor AlcR is shown by NMR and gel
      retardation assay to form a stable complex with oligonucleotide sequences
      comprising the consensus half-site 5'-TGCGG-3'. Apparent microM dissociation
      constants are evaluated by both methods. The measured lifetime of the complex is
      74+/-7 ms at 20 degrees C with the following DNA sequence: 5'
      C1G2T3G4C5G6G7A8T9C10-3'. The major chemical shift variations upon binding
      involve both the two adjacent GC pairs (G6 and G7) and, clearly, the AT pairs at
      both ends of the consensus sequence (T3 and A8), suggesting additional contacts
      of the protein with the DNA. This extensive and strong interaction with the half
      site is another example of the variability in contacts of the fungal DNA-binding
      proteins containing Zn2Cys6 domains with their consensus sites. It is the first
      demonstration that a binuclear cluster protein can bind to DNA as a monomer with
      strong affinity.

PMID- 9187376
TI  - Investigation of the triacylglycerol composition of iceman's mummified tissue by
      high-temperature gas chromatography.
AB  - The pattern of intact triacylglycerols of a skin sample from the 5300-year-old
      Iceman mummy (nicknamed Otzi) was resolved on a diphenyl-dimethylpolysiloxane
      stationary phase by high-temperature gas chromatography. Adipocere from a 64-year
      old glacier mummy as well as recent human subcutaneous fat served as a comparison
      in this study. Qualitatively, the results for mummy samples were similar with
      well-preserved saturated, but decomposed unsaturated, triacylglycerols, the
      latter being predominant in subcutaneous fat. Excellent preservation of
      triacylglycerols with odd carbon numbers and branched acyl chains was observed.
      The results presented here shed new light on the process of mummification.

PMID- 9187375
TI  - Ozone stress modulates amine oxidase and lipoxygenase expression in lentil (Lens
      culinaris) seedlings.
AB  - The effect of ozone stress on polyamine metabolism and membrane lipid
      peroxidation in lentil seedlings through the amine oxidase and lipoxygenase
      activity and expression has been investigated. Ozone is shown to control the
      expression of these enzymes at the transcriptional level, down-regulating the
      amine oxidase gene and up-regulating the lipoxygenase gene. The decrease of amine
      oxidase activity correlated with the increase of putrescine concentration in the
      ozone-treated plantlets, whereas the increase of lipoxygenase activity was
      paralleled by enhanced membrane lipid peroxidation. Finally, polyamines are shown
      to inhibit lipoxygenase activity in lentils.

PMID- 9187377
TI  - Quantification of corticosteroids in human plasma by liquid chromatography
      thermospray mass spectrometry using stable isotope dilution.
AB  - Liquid chromatography-thermospray mass spectrometry (LC-TSP-MS) using isotope
      dilution was investigated for quantitative analysis of cortisol, cortisone,
      prednisolone and prednisone in human plasma. Complete separation attained by a
      LiChroCART Supersupher reversed-phase column and elution with 0.05 M ammonium
      formate-tetrahydrofuran-methanol (180:53:17, v/v/v) resulted in a significantly
      large isotope effect of the deuterium-labeled analogs on the HPLC behavior and
      caused difficulty in quantification. Reduction of the isotope effect on the
      retention times using 0.05 M ammonium formate-acetonitrile (65:35, v/v) permitted
      accurate quantification of cortisol and cortisone by the isotope dilution LC-TSP
      MS, although separation between cortisol and prednisone was incomplete.

PMID- 9187378
TI  - Metabolism of selenite labelled with enriched stable isotope in the bloodstream.
AB  - The metabolism of selenium (Se) in the bloodstream of rats was studied using HPLC
      ICP-MS with an enriched Se stable isotope, and the results were used as Se
      specific indicators for Se nutritional status. Concentration of endogenous Se in
      plasma depended on dietary Se, while changes in concentrations and distributions
      of exogenous Se revealed its metabolic pathway. Namely, selenite was taken up by
      red blood cells and reduced to selenide, and then reappeared in plasma in a form
      bound selectively to albumin within 10 min, disappeared from plasma again within
      30 min after injection. Then, the concentration of labelled Se started to
      increase slowly as selenoprotein P and extracellular glutathione peroxidase, and
      attained a maximum level at about 6 h after injection. The isotope ratio of
      endogenous to exogenous Se concentrations in plasma after 48 h post-injection was
      proposed to represent the Se-specific indicator in plasma reflecting the
      nutritional status of Se.

PMID- 9187379
TI  - Quantification of 1,5-anhydro-D-glucitol in urine by automated borate complex
      anion-exchange chromatography with an immobilized enzyme reactor.
AB  - HPLC using a borate form of a strongly anion-exchange resin column and an
      immobilized enzyme reactor for colorimetric detection was used to quantify
      urinary 1,5-anhydro-D-glucitol. Urine samples were introduced into the system
      every 7 min without any pretreatment, and after separation of interfering
      substances in the column, 1,5-anhydro-D-glucitol was successively detected.
      Quantitative determination of urinary 1,5-anhydro-D-glucitol was possible within
      the 1.2-300 micromol/l range. The coefficient of variance was less than 3% and
      the correlation between results obtained with our system (y) and those obtained
      by gas chromatography-mass spectrometry (x) was y=0.983x-1.287 micromol/l (n=42,
      r=0.998).

PMID- 9187380
TI  - 3,4-Dimethoxybenzylamine as a sensitive pre-column fluorescence derivatization
      reagent for the determination of serotonin in human platelet-poor plasma.
AB  - 3,4-Dimethoxybenzylamine is shown to be a highly sensitive pre-column
      fluorescence derivatization reagent for the determination of serotonin in plasma
      by high-performance liquid chromatography. The reagent reacts selectively with 5
      hydroxyindoles including serotonin in slightly alkaline media in the presence of
      potassium hexacyanoferrate(III) to give highly fluorescent derivatives. The
      derivatives of six standard 5-hydroxyindoles (5-hydroxytryptophan, 5
      hydroxyindole-3-acetic acid, serotonin, 5-hydroxyindole-3-acetamide, N-acetyl-5
      hydroxytryptamine and 5-hydroxytryptophol) are separated within 18 min by
      isocratic elution using acetonitrile-10 mM phosphate buffer (pH 6.0)-50 mM 1
      hexanesulfonic acid on a Wakosil II 5C18RS reversed-phase column. The detection
      limits (signal-to-noise ratio=3) for the indoles were 1.0-5.7 fmol in a 100
      microl injection volume. The method was applied to the measurement of serotonin
      in human platelet-poor plasma.

PMID- 9187381
TI  - Simultaneous determination of glycyl-L-histidyl-L-lysine and its metabolite, L
      histidyl-L-lysine, in rat plasma by high-performance liquid chromatography with
      post-column derivatization.
AB  - A selective and sensitive high-performance liquid chromatographic (HPLC) method
      was developed for the determination of glycyl-L-histidyl-L-lysine (GHK), a liver
      cell growth factor isolated from human plasma, and its metabolite, L-histidyl-L
      lysine (HK), in rat plasma. Both high selectivity and sensitivity were achieved
      by the use of solid-phase extraction with a Bond-Elut Certify cartridge, ion-pair
      chromatography with 1-pentanesulfonate on a 5-microm Capcell Pak C18 UG120 column
      (250x4.6 mm I.D.) with a guard column, and by post-column derivatization with o
      phthalaldehyde (OPA). GHK and HK were extracted from 0.1 ml of rat plasma after
      addition of o-phenanthroline to protect against degradation. The limit of
      detection for GHK and HK were 50 and 15 ng/ml, respectively, and the calibration
      curves were linear in the range 0.1-5.0 microg/ml. The developed method was
      applied to the pharmacokinetic study of GHK after a single dose was administered
      intravenously to rats. GHK was rapidly degraded to HK, which was eliminated
      rapidly.

PMID- 9187382
TI  - Determination of antisense phosphorothioate oligonucleotides and catabolites in
      biological fluids and tissue extracts using anion-exchange high-performance
      liquid chromatography and capillary gel electrophoresis.
AB  - Chemically modified phosphorothioate oligodeoxynucleotides (ODNs) have become
      critical tools for research in the fields of gene expression and experimental
      therapeutics. Bioanalytical assays were developed that utilized fast anion
      exchange high-performance liquid chromatography (HPLC) and capillary gel
      electrophoresis (CGE) for the determination of 20-mer ODNs in biological fluids
      (plasma and urine) and tissues. A 20 mer ODN in the antisense orientation
      directed against DNA methyltransferase (denoted as MT-AS) was studied as the
      model ODN. The anion-exchange HPLC method employed a short column packed with non
      porous polymer support and a ternary gradient elution with 2 M lithium bromide
      containing 30% formamide. Analysis of the MT-AS is accomplished within 5 min with
      a detection limit of approximately 3 ng on-column at 267 nm. For plasma and
      urine, samples were diluted with Nonidet P-40 in 0.9% NaCl and directly injected
      onto the column, resulting in 100% recovery. For tissue homogenates, a protein
      kinase K digestion and phenol-chloroform extraction were used, with an average
      recovery of about 50%. Since the HPLC assay cannot provide one-base separation,
      biological samples were also processed by an anion-exchange solid-phase
      extraction and a CGE method to characterize MT-AS and its catabolites of 15-20
      mer, species most relevant to biological activity. One base separation, under an
      electric field of 400 V/cm at room temperature, was achieved for a mixture of 15
      20-mer with about 50 pg injected. Assay validation studies revealed that the
      combined HPLC-CGE methods are accurate, reproducible and specific for the
      determination of MT-AS and its catabolites in biological fluids and tissue
      homogenates, and can be used for the pharmacokinetic characterization of MT-AS.

PMID- 9187383
TI  - Determination of total iodine in biological material by alkaline ashing and
      column-switching ion-pair liquid chromatography.
AB  - A method for the determination of total iodine in biological material has been
      developed. The method combines alkaline ashing with a selective and sensitive
      column-switching ion-pair HPLC technique. The ashing procedure which converts the
      organically bound iodine to iodide is miniaturised and requires only about 100 mg
      of sample. The first column of the column-switching system is polymer based and
      can therefore withstand the alkaline pH obtained after ashing. On the analytical
      column the iodide is separated as an ion-pair with tetrabutyl ammonium
      hydrogensulphate. The method has been applied to samples from whole blood, urine,
      liver, lung, carcass, and a sample throughput of at least 50 samples per day can
      be achieved. Validation studies by spiking experiments showed the precision to be
      better than 10% R.S.D. for all matrices with recoveries in the range 87-97%. The
      method has been applied for samples with an iodine content in the range 0.07-1060
      microg/g.

PMID- 9187384
TI  - Rapid liquid-liquid extraction of cocaine from urine for gas chromatographic-mass
      spectrometric analysis.
AB  - A novel, simple and economic liquid-liquid extraction method for isolating
      cocaine from urine was developed utilizing gas chromatography-mass spectrometry
      (GC-MS) for analysis and quantification. The use of a single nonpolar organic
      solvent allowed only nonpolar analytes to be extracted from the biological fluid,
      and consequently, no derivatization step was necessary before GC-MS analysis.
      Large numbers of specimens (>60) can be extracted in approximately 3 h with this
      procedure. The method is highly precise (C.V. <7%), accurate (>98%), sensitive
      (limit of detection of 5 ng/ml) and has a mean recovery of 48.8%.

PMID- 9187385
TI  - Gas chromatographic-mass spectrometric quantitation of urinary buprenorphine and
      norbuprenorphine after derivatization by direct extractive alkylation.
AB  - A gas chromatographic-mass spectrometric procedure for the quantitation of
      buprenorphine and norbuprenorphine has been developed in which the analytes were
      converted, after enzyme hydrolysis, to their methyl derivatives by direct
      extractive alkylation using tetrahexylammonium hydrogen sulphate phase transfer
      reagent and iodomethane dissolved in tert.-butylmethyl ether. The procedure
      utilised a sample volume of 2 ml and gave a detection limit of 0.2 ng ml(-1) for
      buprenorphine and norbuprenorphine. The buprenorphine and norbuprenorphine
      standard curves were linear in the concentration range of 1-100 ng ml(-1) with
      r=0.999. The coefficients of variation for the intra-run precision were 1.3% for
      buprenorphine and 8.8% for norbuprenorphine (n=10). The coefficients of variation
      for the inter-run precision were 7.7% for buprenorphine and 10.1% for
      norbuprenorphine (n=5). The method recovery was 92% (C.V.=3.3%) for buprenorphine
      and 104% (C.V.=2.9%) for norbuprenorphine (n=10).

PMID- 9187386
TI  - Fast specific separation and sensitive quantification of bactericidal and
      sporicidal aldehydes by high-performance liquid chromatography: example of
      glutaraldehyde determination.
AB  - This article describes the design and the validation of the HPLC determination of
      glutaraldehyde at g/l and mg/l concentrations, after derivatization by 2,4
      dinitrophenylhydrazine and using the external standard method. At low
      concentrations, the reaction mixture needs to be heated and a weight ratio of 500
      for the 2,4-dinitrophenylhydrazine reagent and the glutaraldehyde ensures a
      linear calibration curve. In contrast, high concentrations do not require heating
      of the reaction mixture and a weight ratio of 32 proved to be sufficient. The
      optimized HPLC method has been validated for both ranges of concentrations.
      Between 1.25 and 10 mg/l, the content can be determined by the external standard
      method, with a repeatability of 0.5%. The detection limit is 0.2 mg/l. Between
      0.31 and 2.5 g/l, the content can also be determined by the external standard
      method, with a repeatability of 0.4%. Finally, statistical analysis has
      demonstrated that aqueous solutions of glutaraldehyde are stable for at least
      three days at 4 degrees C within the mg to g range.

PMID- 9187387
TI  - Rapid method to determine sphinganine/sphingosine in human and animal urine as a
      biomarker for fumonisin exposure.
AB  - The widespread occurrence of fumonisins in maize and maize-based foods and feeds
      demands the development of rapid and reliable methods for the analysis of
      suitable biomarkers in biological fluids in order to assess human and animal
      exposure to these important mycotoxins. The increase in the ratio of free
      sphinganine/sphingosine (SA/SO) in urine has been recently proposed as a
      biomarker to evaluate exposure to fumonisins. The presently available method for
      the determination of SA and SO in biological samples is labor intensive, time
      consuming and insufficiently accurate. A new method has been proposed for the
      determination of SA and SO in human and animal urine which is more precise and
      accurate, and drastically reduces the number of steps during extraction and clean
      up. The method is essentially based on the use of silica minicolumn clean-up of
      the chloroform extract from alkalinized urine. The final extract is derivatized
      with o-phthaldialdehyde reagent and SO and SA are determined by reversed-phase
      HPLC with fluorimetric detector. Urine samples spiked with SO, SA standards at
      concentrations ranging from 1.5 to 15 ng/ml have given mean recoveries higher
      than 80% and precision (coefficient of variation) lower than 10%. Detection limit
      for SO and SA was 0.1 ng/ml.

PMID- 9187388
TI  - Simultaneous determination of midazolam and its metabolites 1-hydroxymidazolam
      and 4-hydroxymidazolam in human serum using gas chromatography-mass spectrometry.
AB  - A method for the quantitation of midazolam and its metabolites 1-hydroxymidazolam
      and 4-hydroxymidazolam from human serum capable of monitoring concentrations
      achieved under therapeutic conditions is presented. The substances were extracted
      under basic conditions with toluene and the hydroxy metabolites transformed to
      their tert-butyldimethylsilyl derivatives with N-(tert-butyldimethylsilyl)-N
      methyltrifluoroacetamide. The samples were measured by gas chromatography-mass
      spectrometry. The limits of detection are 0.2 ng ml(-1) for midazolam and 0.1 ng
      ml(-1) for 1-hydroxy- and 4-hydroxymidazolam. The coefficients of variation are
      3.9% at 5 ng ml(-1) for midazolam, 6.7% at 2 ng ml(-1) for 1-hydroxymidazolam and
      8.8% (22.2%) at 0.5 (0.2) ng ml(-1) for 4-hydroxymidazolam.

PMID- 9187389
TI  - High-performance liquid chromatography-ionspray mass spectrometry for the
      specific determination of digoxin and some related cardiac glycosides in human
      plasma.
AB  - An original method based upon high-performance liquid chromatography coupled to
      ionspray mass spectrometry (HPLC-ISP-MS) has been developed for the
      identification and quantification in plasma of several cardiac glycosides, namely
      digoxin, digitoxin, lanatoside C and acetyldigitoxin. After single-step liquid
      liquid extraction by chloroform-2-propanol (95:5, v/v) at pH 9.5 using oleandrin
      as an internal standard, solutes are separated on a 4 microm NovaPak C18 (Waters)
      column (150x2.0 mm, I.D.), using a gradient of acetonitrile-2 mM NH4COOH, pH 3
      buffer (flow-rate 200 microl/min, post-column split 1:3). Detection is done by a
      Perkin-Elmer Sciex API-100 mass analyzer equipped with an ISP interface. In most
      instances the major ion observed is not [M+H]+ as expected, but [M+NH4]+. The
      mean retention times (min) are: lanatoside C, 5.74; digoxin, 6.00; digitoxin,
      8.08, oleandrin, 8.30, acetyldigitoxin, 8.66 and 9.01 (isomers alpha and beta,
      respectively). The lower limits of detection in single ion monitoring mode range
      from 0.15 ng/ml (alpha- and beta-acetyldigitoxin) to 0.60 ng/ml (lanatoside C),
      making the method less sensitive than radioimmunoassay, whereas it is much more
      specific.

PMID- 9187391
TI  - Determination of imipenem in plasma by high-performance liquid chromatography for
      pharmacokinetic studies in patients.
AB  - A rapid and simple HPLC method is described for the determination of imipenem in
      human plasma. After blood collection, plasma was separated by centrifugation and
      immediately stabilized with 3-morpholinopropanesulfonic acid (MOPS) and ethylene
      glycol solution (1:1). The sample preparation, before injection into HPLC, was
      ultrafiltration. The mobile phase was boric acid buffer. The imipenem was
      detected at 300 nm and cilastatin sodium, coadministered, did not interfere.
      Calibration curves in human plasma were linear from 0.1 to 100 microg/ml. The
      limit of detection was 0.030 microg/ml. Inter-day precision at 0.1 microg/ml,
      determined as the coefficient of variation, was 6.26%. Only 250 microl of plasma
      was required in our assay. Due to the limited stability of imipenem [G.B. Smith
      et al., J. Pharm. Sci., 79 (1990) 732], stability studies in plasma were done to
      establish appropriate storage conditions. The assay was applied to
      pharmacokinetic studies in patients.

PMID- 9187390
TI  - Shift of the high-performance liquid chromatographic retention times of
      metabolites in relation to the original drug on an RP8 column with acidic mobile
      phase.
AB  - The effect of the structural change in the metabolization of drugs on the HPLC
      retention time with an RP8 column with an acetonitrile-phosphate buffer (pH 2.3)
      as the mobile phase was investigated at model compound pairs of 29
      functionalization reactions. A more or less typical region for T(M)=log(k'M/k'D)
      was found for each of these reactions (with k'M and k'D being the capacity
      factors of the metabolite and the drug, respectively), which can be explained by
      an increase or a decrease of the hydrophilic properties caused by the structural
      change. This effect is superimposed by an essential influence of the unchanged
      part of the molecule and in some cases by special intramolecular interactions
      like the hydrogen bond. Despite the more complicated structure of real drugs the
      results obtained at the model compound pairs were confirmed for most of the 55
      metabolite/drug pairs. The practical use of the T(M) values as a support to
      distinguish between different metabolites in the HPLC-DAD analysis of
      intoxications is demonstrated with cases of poisoning with diphenhydramine,
      propafenone and methaqualone.

PMID- 9187392
TI  - Stereoselective high-performance liquid chromatography determination of
      propranolol and 4-hydroxypropranolol in human plasma after pre-column
      derivatization.
AB  - A stereoselective reversed-phase HPLC assay to quantify S-(-) and R-(+)
      enantiomers of propranolol and 4-hydroxypropranolol in human plasma was
      developed. The method involved liquid-liquid extraction for sample clean-up and
      employed 2,3,4,6-tetra-O-acetyl-beta-glucopyranosyl isothiocyanate as a pre
      column chiral derivatization reagent. The internal standard used was 4
      methylpropranolol. The derivatized products were separated on an Altex C18 column
      using a mixture of acetonitrile-water-phosphoric acid-triethylamine
      (58:42:0.1:0.06 and 50:50:0.15:0.06, v/v, for propranolol and 4
      hydroxypropranolol, respectively) as mobile phase. The detection of propranolol
      derivatives was made at lambda(ex)=280 nm and lambda(em)=325 nm, and the
      corresponding 325 and 400 nm were used for 4-hydroxypropranolol derivatives. The
      assay was linear from 1 to 100 ng/ml and from 2 to 50 ng/ml using 0.5 ml of human
      plasma for propranolol and 4-hydroxypropranolol enantiomers, respectively. The
      present assay is used to quantify the enantiomers of propranolol and 4
      hydroxypropranolol, respectively, in human plasma for pharmacokinetic studies.

PMID- 9187393
TI  - High-performance liquid chromatography determination of praziquantel enantiomers
      in human serum using a reversed-phase cellulose-based chiral stationary phase and
      disc solid-phase extraction.
AB  - A sensitive HPLC method for the quantification of praziquantel enantiomers in
      human serum is described. The method involves the use of a novel disc solid-phase
      extraction for sample clean-up prior to HPLC analysis and is also free of
      interference from trans-4-hydroxypraziquantel, the major metabolite of
      praziquantel. Chromatographic resolution of the enantiomers was performed on a
      reversed-phase cellulose-based chiral column (Chiralcel OJ-R) under isocratic
      conditions using a mobile phase consisting of 0.1 M sodium perchlorate
      acetonitrile (66:34, v/v) at a flow-rate of 0.5 ml/min. Recoveries for R-(-)- and
      S-(+)-praziquantel enantiomers were in the range of 84-89% at 50-500 ng/ml
      levels. Intra-day and inter-day precisions calculated as R.S.D. were in the
      ranges of 3-8% and 1-8% for both enantiomers, respectively. Intra-day and inter
      day accuracies calculated as percent error were in the 0.2-5% and 0.3-8% ranges
      for both enantiomers, respectively. Linear calibration curves were in the
      concentration range 10-600 ng/ml for each enantiomer in serum. The limit of
      quantification of each enantiomer was 10 ng/ml. The detection limit for each
      enantiomer in serum using a UV detector set at 210 nm was 5 ng/ml (S/N=2).

PMID- 9187394
TI  - Determination of amiprilose in human plasma by high-performance liquid
      chromatography with fluorimetric detection.
AB  - A reversed-phase HPLC method to quantify amiprilose in human plasma is described.
      The method involves liquid-liquid extraction of amiprilose and the internal
      standard from plasma. The extracted compounds are derivatized with 1,8-naphthalic
      dicarboxylic acid using 2-chloro-1-methylpyridinium iodide as a coupling reagent.
      The derivatized products are separated on a reversed-phase column and monitored
      fluorimetrically using 280 nm and 340 nm as excitation and emission wavelengths,
      respectively. The derivatized products which exhibit two peaks on chromatogram,
      are shown to be the interconvertible isomers. This assay has been used in
      pharmacokinetic studies of amiprilose in humans.

PMID- 9187395
TI  - Simultaneous determination of artesunic acid and dihydroartemisinin in blood
      plasma by high-performance liquid chromatography for application in clinical
      pharmacological studies.
AB  - A selective reproducible high-performance liquid chromatographic assay for the
      simultaneous quantitative determination of the antimalarial compound artesunic
      acid (ARS), dihydroartemisinin (DQHS) and artemisinin (QHS), as internal
      standard, is described. After extraction from plasma, ARS and DQHS were analysed
      using an Econosil C8 column and a mobile phase of acetonitrile-0.05 M acetic acid
      (42:58, v/v) adjusted to pH 5.0 and electrochemical detection in the reductive
      mode. The mean recovery of ARS and DQHS over a concentration range of 50-200
      ng/ml was 75.5% and 93.5%, respectively. The within-day coefficients of variation
      were 4.2-7.4% for ARS and 2.6-4.9% for DQHS. The day-to-day coefficients of
      variation were 1.6-9.6% and 0.5-8.3%, respectively. The minimum detectable
      concentration for ARS and DQHS in plasma was 4.0 ng/ml for both compounds. The
      method was found to be suitable for use in clinical pharmacological studies.

PMID- 9187396
TI  - High-performance liquid chromatographic determination of acrolein as a marker for
      cyclophosphamide bioactivation in human liver microsomes.
AB  - A high-performance liquid chromatographic method for the quantification of
      acrolein following incubation of cyclophosphamide (CP) with human liver
      microsomes was developed. Based on the formation of the fluorescent derivative 7
      hydroxyquinoline by condensation of acrolein with 3-aminophenol quantitation was
      performed without prior extraction or other sample cleanup procedures. The method
      showed sufficient sensitivity with a limit of detection of 5 ng/ml and a limit of
      quantification of 10 ng/ml. The suitability of the method is shown for enzyme
      kinetic studies.

PMID- 9187397
TI  - Reversed-phase high-performance liquid chromatographic determination of the new
      antitumor agent cyclopentenyl cytosine in biological fluids.
AB  - Cyclopentenyl cytosine (CPE-C) is a synthetic carbocyclic nucleoside that
      possesses diverse antitumor and antiviral activity. CPE-C has been studied
      extensively at the preclinical level and has been evaluated in a Phase I clinical
      trial involving patients with solid tumors. A narrow-bore, reversed-phase HPLC
      method that has been developed for the sensitive measurement of CPE-C in plasma
      and urine in order to carry out these studies is described. Covalent solid-phase
      extraction based on an immobilized phenylboronic acid ligand is employed to
      isolate both CPE-C and endogenous ribonucleosides from the biological matrix
      selectively and efficiently. This is followed by isocratic elution of the extract
      with pH 5.0, 0.1 M ammonium formate buffer at 0.150 ml/min on a tandem,
      switchable, C18 narrow-bore (2.1 mm I.D.) column system in which the precolumn is
      automatically backflushed to eliminate late-eluting components. UV detection at
      278 nm provides a limit of quantitation of 0.1 microM for CPE-C in rat and human
      plasma with a precision better than 4% for the range 1-20 microM in rat plasma.
      Application of this assay to the determination of the bolus dose plasma kinetics
      and disposition of 2 mg/kg CPE-C in rats is illustrated. This method is amenable
      to partial automation and is well-suited for the analysis of clinical samples.

PMID- 9187398
TI  - Quantitation of beta-lapachone and 3-hydroxy-beta-lapachone in human plasma
      samples by reversed-phase high-performance liquid chromatography.
AB  - beta-Lapachone is an o-naphthoquinone found to have in vitro cytotoxicity in
      cancer cells, type I human immunodeficiency virus, and fungi. Analytical methods
      for evaluating beta-lapachone in biological fluids using high-performance liquid
      chromatography (HPLC) have not been published. The reversed-phase HPLC method
      described in this report utilizes liquid extraction of a 0.5-ml plasma sample
      with average recoveries of 67+/-10.8% and 70+/-10.3% for beta-lapachone and 3
      hydroxy-beta-lapachone, respectively. Sensitivity of the assay using ultraviolet
      (UV) detection at 256 nm is 15 ng ml(-1) from a 100 microl injection. Plasma
      standards for beta-lapachone and 3-hydroxy-beta-lapachone are linear with no
      significant difference in slope between the compounds. The retention times of 2.7
      min for 3-hydroxy-beta-lapachone and 5.9 min for beta-lapachone result in a clean
      separation permitting use of the same assay procedure without modification for
      both compounds. This assay offers the advantage that either beta-lapachone or 3
      hydroxy-beta-lapachone can serve as the internal standard, depending on which
      compound is being analyzed.

PMID- 9187399
TI  - Determination of flunixin in equine urine and serum by capillary electrophoresis.
AB  - A capillary electrophoresis (CE) and a solid-phase extraction method was
      developed for the determination of flunixin in equine urine and serum. The
      suitable CE run conditions were described. The factors affecting flunixin
      recovery rates were investigated and optimum solid-phase extraction conditions
      for flunixin in equine urine and serum were established. Limits of detection and
      quantitation were 3.4 and 5.6 ng/ml for serum and 16.9 and 33.1 ng/ml for urine,
      respectively. The recoveries exceeded 96% for urine and 79% for serum. Urine
      samples from race horses and urine and serum samples from a mare administrated
      with flunixin were analyzed with this procedure.

PMID- 9187400
TI  - Determination of bromhexine and ambroxol in pharmaceutical dosage forms, urine
      and blood serum.
AB  - Data presented in this paper show that bromhexine and its pharmacologically
      active metabolite can easily be determined by capillary zone electrophoresis. The
      composition of the running buffer had a significant effect on the reproducibility
      of the migration time for which a carrier solution containing 30 mM phosphate
      buffer (pH 3.0), 5 M urea and 10% (v/v) acetonitrile was used. The method was
      validated with respect to its response linearity and reproducibility. The method
      is suitable for the determination of bromhexine and ambroxol in several samples
      such as pharmaceuticals, urine and serum. Photodiode-array detection permitted
      the rapid identification of both drugs in the sample analyzed.

PMID- 9187401
TI  - Microbore high-performance liquid chromatographic method for measuring
      acetylcholine in microdialysis samples: optimizing performance of platinum
      electrodes.
AB  - A microbore high-performance liquid chromatographic method with electrochemical
      detection was applied to the measurement of acetylcholine in microdialysis
      samples. There was an excellent linear relationship (r=0.99998) between the
      concentration of acetylcholine injected onto the column and the peak height (0.05
      10 pmol/5 microl). During the validation of this method, we noticed that the peak
      height for acetylcholine decreased over time, coupled with the appearance of a
      brown coating on the surface of the platinum electrode. Repeated measurement of
      acetylcholine standards which had been stored at 4 degrees C and -20 degrees C
      before and after cleaning the platinum electrode with ethanol or methanol
      indicated that the decrease in the peak height of acetylcholine is caused by a
      decrease in sensitivity of the electrode itself. Results with a second microbore
      high-performance liquid chromatographic system confirmed these findings. On the
      basis of these results, we recommend that the platinum electrode is cleaned
      periodically with ethanol or methanol, and that quantitation is regularly
      calibrated with external acetylcholine.

PMID- 9187402
TI  - Total plasma homocysteine determination by liquid chromatography before and after
      methionine loading. Results in cerebrovascular disease.
AB  - Elevated homocysteine (HCY) levels in tissues and blood are associated with
      premature occlusive diseases. A number of techniques have been developed to assay
      HCY, including high-performance liquid chromatography (HPLC) with fluorimetric or
      electrochemical detection, and radioenzymatic methods. The present study
      evaluated the adaptation of a liquid chromatographic, ion-exchange technique with
      postcolumn derivatization using ninhydrin. Fasting and moreover post-methionine
      load total plasma HCY were assayed in 50 patients three months after a stroke and
      in 20 age-matched controls. Ion-exchange liquid chromatography was performed on
      an amino acid analyzer using a modified procedure to improve methionine and HCY
      separation. HCY values in the fasting state were moderately but significantly
      increased (P<0.05) in the patients compared to the controls: 10.5+/-3.4 versus
      9.3+/-2.3 micromol/l. The difference between the two groups was amplified in post
      load HCY results, which were significantly increased (P<0.05) in the patients:
      41.6+/-17.8 versus 29.2+/-5.5 micromol/l in controls. The relationship between
      cerebrovascular disease and impaired HCY metabolism has previously been
      emphasized by other investigators. Our findings suggest that certain inherited
      and/or acquired HCY disorders observed in the fasting state (14%) and especially
      in post-methionine load conditions (32%) may occur during acute disease, and that
      total plasma HCY can be determined by ion-exchange chromatography even after oral
      methionine loading.

PMID- 9187404
TI  - Determination of dexamethasone in tears by capillary electrophoresis.
AB  - A selective capillary zone electrophoresis (CZE) microassay was developed for the
      simultaneous determination of dexamethasone phosphate and its major metabolite,
      dexamethasone, in tears. The calibration was carried out in the biological matrix
      with indoprofen as an internal standard which allowed the separation of
      dexamethasone phosphate and dexamethasone from the tear constituents. The limits
      of detection and quantification of the assay were 0.5 and 2.0 microg ml(-1),
      respectively. This quantification method is essential for the in vivo
      determination of dexamethasone concentration-time profiles in tears after
      application of the antiinflammatory drug.

PMID- 9187403
TI  - Hydroxyindole-O-methyltransferase activity assay using high-performance liquid
      chromatography with fluorometric detection: determination of melatonin
      enzymatically formed from N-acetylserotonin and S-adenosyl-L-methionine.
AB  - A reliable, sensitive and rapid assay has been developed for determining the
      activity of hydroxyindole-O-methyltransferase (HIOMT; S-adenosyl-L-methionine:N
      acetylserotonin-O-methyltransferase; EC 2.1.1.4), which catalyzes the final step
      in the melatonin (N-acetyl-5-methoxytryptamine) biosynthetic pathway. This method
      is based on the separation and detection of melatonin formed enzymatically from N
      acetylserotonin and S-adenosyl-L-methionine, by high-performance liquid
      chromatography with fluorometric detection. The detection limit for melatonin
      formed per sample was as low as 150 fmol, indicating that the sensitivity of this
      assay was comparable to that of a radioisotopic assay. The assay was applied to
      the determination of HIOMT activity in rat pineal gland. The HIOMT activity
      obtained in this study was comparable with, or slightly lower than those reported
      previously using radioisotopic assays.

PMID- 9187405
TI  - Simplified solid-phase extraction method for determination of dihydroergotamine
      in rabbit and human serum using high-performance liquid chromatography with
      fluorescence detection.
AB  - A rapid, selective and sensitive method for the determination of
      dihydroergotamine (DHE) in serum was developed. Dihydroergocristine (DHEC) was
      used as an internal standard. Human and rabbit serum samples were extracted using
      commercial solid-phase cyano (CN) columns. Proteins were washed from these
      columns with pure acetonitrile, resulting in clean extracts. Extracts were
      subsequently separated by HPLC in an isocratic way, using a reversed-phase C18
      analytical column. Fluorometric detection was performed at excitation and
      emission wavelengths of 277 and 348 nm, respectively. Calibration curves with
      amounts of DHE ranging from 2 to 32 ng, were linear. The limit of detection found
      for DHE was 0.2 ng, extracted from 0.5 ml rabbit or from 2.5 ml human serum. The
      limit of quantification in serum of both species was 0.7 ng. The method has been
      shown to be suitable for monitoring DHE in serum during pharmacokinetic studies
      in rabbits.

PMID- 9187407
TI  - Clean-up and re-use of kieselguhr (Extrelut) for liquid-liquid extraction of
      urinary cortisol.
AB  - Cortisol was isolated from human urine using kieselguhr (Extrelut)-filled
      columns. After use, Extrelut was cleaned-up once with distilled water and twice
      with ethanol. Before re-use, the cleaned-up kieselguhr was dried for 24 h by a
      warm air stream. The comparison of cortisol recovery from human urine and HPLC
      chromatograms of urinary extracts show that Extrelut can be repeatedly used for
      liquid-liquid extraction of urinary cortisol.

PMID- 9187406
TI  - High-performance liquid chromatographic assay of 5-fluorouracil in human
      erythrocytes, plasma and whole blood.
AB  - A HPLC assay method was modified and validated for the determination of 5
      fluorouracil in human red blood cells, plasma and whole blood with a two-fold
      increased sensitivity (detection limit=10 ng/ml). The assay was linear from 25 to
      1500 ng/ml and the accuracy ranged from 96.7 to 103.2% at 25 ng/ml, 94.8 to 99.4%
      at 500 ng/ml, and 98.9 to 99.5% at 1500 ng/ml. Intra-assay and inter-assay
      coefficients of variation were less than 8% over the range of concentrations and
      less than 8% over 10 days of analysis. After intravenous bolus and infusion of 5
      fluorouracil in patients with colorectal cancer, the concentrations of 5
      fluorouracil in whole blood were 108-111% of plasma concentrations, while packed
      red blood cells levels were 8-15% of plasma concentrations in the five patients
      studied. By utilising basic analytical hardware, this represents an accurate,
      precise, reproducible and affordable method for 5-fluorouracil pharmacokinetics
      investigation and therapeutic drug monitoring.

PMID- 9187408
TI  - Simple, rapid and sensitive method for the determination of indomethacin in
      plasma by high-performance liquid chromatography with ultraviolet detection.
AB  - A micro method for determination of indomethacin in plasma was developed.
      Following deproteinization of plasma with acetonitrile containing internal
      standard (mefenamic acid), the separation of indomethacin and internal standard
      was achieved by high-performance liquid chromatography using a 7 microm
      LiChrosorb-RP18 column (250x4 mm I.D.) at 50 degrees C. The mobile phase was 6 mM
      phosphoric acid-acetonitrile (50:50). The flow-rate was kept at 2.0 ml/min and
      the column effluent was monitored at 205 nm. The coefficients of variation of the
      method estimated at 0.2 and 1.0 microg/ml were 4.2 and 2.3%, and the detection
      limit of the drug was about 0.05 microg/ml (S/N=5). The method requires minimum
      pretreatment of the plasma with a small sample volume (25 microl), and is very
      suitable for therapeutic drug monitoring of indomethacin in premature infants
      with symptomatic patent ductus arteriosus.

PMID- 9187409
TI  - Damage of charge-dependent renal tubular reabsorption causes diabetic
      microproteinuria.
AB  - More negatively-charged proteins are harder to pass through the glomerular charge
      barrier (GCB) and to be reabsorbed by renal tubules. Although the glycation of
      albumin increases its negative charge compared to non-glycated albumin, the
      glycation of transferrin does not change its charge. This difference enabled us
      to examine the charge-dependent renal function in diabetic proteinuria. The
      percentage of urinary glycated transferrin (serum %G-transferrin) positively
      correlated with serum fructosamine concentrations and the percentage of serum
      glycated albumin (serum %G-albumin) in all subjects. Urinary concentrations of
      transferrin and beta 2-microglobulin strongly correlated in diabetic patients
      with microproteinuria, while no significant correlation was observed in subjects
      with diabetic macroproteinuria or non-diabetic proteinuria. Urine/serum (U/S)
      ratio of %G-albumin in the patients with diabetic proteinuria was significantly
      lower than that in subjects with non-diabetic proteinuria, while no difference of
      the U/S ratio of %G-transferrin was observed between any groups. Furthermore, U
      %G-transferrin/U-%G-albumin ratio was highest in the diabetic patients with
      microproteinuria. These results lead to the conclusion that the initial damage in
      diabetic kidney causing microproteinuria starts with the dysfunction of charge
      dependent tubular reabsorption prior to a loss of GCB.

PMID- 9187410
TI  - Albuminuria is directly associated with increased plasma PAI-1 and factor VII
      levels in NIDDM patients.
AB  - Increased plasma plasminogen activator inhibitor type 1 (PAI-1), coagulation
      factor VII (FVII) and fibrinogen levels have been recognized as risk factors for
      cardiovascular disease. Because a substantially high incidence of cardiovascular
      disease has been reported in diabetic patients with nephropathy compared with
      those without nephropathy, we measured plasma levels of PAI-1, FVII activity and
      fibrinogen in non-insulin-dependent diabetic patients (NIDDM) with
      normoalbuminuria (without nephropathy), microalbuminuria (incipient nephropathy)
      and macroalbuminuria (overt nephropathy). PAI-1 and FVII levels were
      significantly increased in NIDDM with overt nephropathy compared with NIDDM
      without nephropathy. Fibrinogen levels were comparable between the patients with
      normo-, micro- and macro-albuminuria. Univariate regression analysis indicated
      that PAI-1 and FVII levels were significantly correlated with the albumin
      excretion rate (AER) in urine. PAI-1, FVII and fibrinogen levels were
      significantly correlated with the degree of insulin resistance estimated by the
      steady state plasma glucose concentration (SSPG) during the continuous infusion
      of glucose, insulin and octreotide. PAI-1 levels were correlated with plasma
      triglyceride (TG) levels. Multiple regression analysis revealed that AER was
      significantly associated with PAI-1 and FVII levels, whereas TG lost significant
      correlation with PAI-1 when AER, SSPG and plasma TG were entered as independent
      variables. SSPG retained an independent correlation with fibrinogen, PAI-1 and
      FVII levels. These results suggest that elevated plasma levels of PAI-1 and FVII
      in NIDDM patients with nephropathy are directly associated with renal damage,
      whereas insulin resistance widely regulates hemostatic components in NIDDM
      patients, irrespective of the presence of nephropathy.

PMID- 9187412
TI  - Renal threshold for glucose in non-insulin-dependent diabetic patients.
AB  - Measurement of glycosuria is still widely used for home monitoring of glycaemia
      control in non-insulin-dependent diabetes (NIDDM). This method has been
      criticized because the renal threshold for glucose (RTglu) varies between
      subjects. In order to evaluate the validity of RTglu by measuring corresponding
      measurements of blood and urine glucose in NIDDM patients, we studied the
      blood/urine glucose relationship in 24 NIDDM patients. RTglu estimated from 75
      contemporary blood and urine glucose concentrations measured at home by each
      patient (h-RTglu) was compared with RTglu measured by a hyperglycaemic glucose
      clamp (c-RTglu). H-RTglu and c-RTglu, being 7.6 mmol/1 (range 5.5-12.4) and 10.3
      mmol/1 (6.2-12.3) respectively (P < 0.005), were weakly correlated (R(S) = 0.35,
      P = 0.15). In conclusion, c-RTglu varies two-fold between NIDDM patients. RTglu
      detected by home monitored urine and blood glucose determinations underestimates
      the true RTglu, probably due to the splay phenomenon. However, the method for
      detection of RTglu used by us seems of clinical relevance, since it reflects the
      individual blood glucose level at which glucose is detectable in the urine.

PMID- 9187411
TI  - Evaluation of microangiopathy of the skin in patients with non-insulin-dependent
      diabetes mellitus by laser Doppler flowmetry; microvasodilatory responses to
      beraprost sodium.
AB  - To determine the relationship of skin microangiopathy and other diabetic
      microvascular complications, we measured changes in skin blood flow after the
      administration of the prostacyclin (PGI2) analogue, beraprost sodium (BPS), in 82
      patients with non-insulin-dependent diabetes mellitus and 20 healthy subjects.
      The diabetic patients had various degrees of retinopathy and nephropathy. Using
      laser Doppler flowmetry we measured skin blood flow at the dorsum of the right
      big toe at various times after the administration of 40 micrograms BPS and
      calculated the blood flow change (delta flux = peak flux--basal flux). We also
      determined the ankle pressure index (API), an ankle/brachial systolic pressure
      ratio. The basal blood flow was higher in healthy subjects than in diabetic
      patients (P < 0.001). BPS significantly increased blood flow in both diabetic
      patients and healthy subjects (P < 0.001). In all 102 subjects delta flux was
      positively correlated with the API (R = 0.40, P < 0.001). Despite no differences
      in API among the diabetic retinopathy and nephropathy subgroups, the delta flux
      in diabetic patients with progressive retinopathy and macroalbuminuria was
      significantly lower than in healthy subjects or in diabetic patients with less
      severe retinopathy and nephropathy (P < 0.05). The results suggested that BPS
      increases skin blood flow and the flow increase induced by BPS is related partly
      to the levels of API. The effect of BPS on skin blood flow decreased with an
      increases in the severity of retinopathy and nephropathy. Diabetic skin
      microangiopathy appears to coexist with other microvascular diabetic
      complications and may be proportional to their severity.

PMID- 9187413
TI  - A non-linear effect of ambient temperature on apparent glucose tolerance.
AB  - Increased ambient temperature affects apparent oral glucose tolerance to an
      extent which may have clinical implications for the diagnosis of impaired glucose
      tolerance and gestational diabetes. As a first step in order to better define the
      nature of this effect, we have examined, in a climate chamber, the effects of
      ambient temperature at four levels (20, 25, 30, and 35 degrees C) on glucose and
      insulin responses to a standard 75 g oral glucose tolerance test in seven non
      diabetic male subjects. Plasma glucose responses to ambient temperature were
      compared with the responses of core (auditory canal) and skin temperatures. The 2
      h plasma glucose was affected in a nonlinear manner by ambient temperature (5.4
      +/- 0.2, 5.3 +/- 0.4, 6.5 +/- 0.3, 6.4 +/- 0.4 mmol/l at 20, 25, 30, and 35
      degrees C, P = 0.015) with the effect localised between 25 and 30 degrees C (P =
      0.012). Core temperature responded in a similar manner (36.6 +/- 0.1, 36.6 +/-
      0.1, 36.9 +/- 0.1, 37.0 +/- 0.1, (P = 0.0005) with the effect localised 25 and 30
      degrees C (P = 0.011). However skin temperature increased significantly with each
      5 degrees C increase in ambient temperature (30.2 +/- 0.5, 33.0 +/- 0.5, 34.2 +/-
      0.2, 35.2 +/- 0.2, P < or = 0.0001). We conclude that the acute effect of ambient
      temperature on apparent glucose tolerance is most likely due to redistribution of
      blood flow between cutaneous and visceral beds driven by changes in core
      temperature. The absence of temperature effects between the two lowest, and
      between the two highest temperatures, provides workable guidelines for the
      standardisation of conditions during oral glucose tolerance tests in
      circumstances where temperature may have clinically significant effects.

PMID- 9187414
TI  - A 15-year follow-up study of patients with non-insulin-dependent diabetes
      mellitus (NIDDM) in Osaka, Japan. Factors predictive of the prognosis of diabetic
      patients.
AB  - Risk factors related to the prognosis of diabetic patients were studied in a
      follow-up study of 1939 patients with non-insulin-dependent diabetes mellitus
      (NIDDM) for a mean observation period of 15 years at our institute. Age at entry
      into the study was the most powerful risk factor related to the survival of
      diabetic patients in this study. Moreover, the risk of death, computed in
      relation to baseline factors, was significantly increased in male patients; in
      patients with fasting plasma glucose (FPG) levels greater than 140 mg/dl, with
      hypertension, with diabetic retinopathy or with proteinuria; and in patients
      treated with an oral hypoglycemic agent of insulin at baseline, even after
      correction for age. The baseline factors were compared between the groups of
      patients who were alive and who had died at the end of the follow-up study.
      Greater age at onset of NIDDM and at entry into the study, higher FPG level,
      higher systolic and diastolic blood pressure, as well as an increase in the
      proportion of male patients and in patients with ischemic ECG changes, with
      diabetic retinopathy, with proteinuria, and with treatment with an oral
      hypoglycemic agent of insulin, were observed in the group of deceased patients.
      Furthermore, multiple logistic analysis indicated a significant relationship of
      age at entry, FPG, hypertension, retinopathy, proteinuria and therapeutic regimen
      to prognosis. We also found that the baseline factors predictive of prognosis
      were very different in each age group.

PMID- 9187415
TI  - Patients with diabetes mellitus and atherosclerosis; a role for cytomegalovirus?
AB  - Diabetic patients are known to have an impaired immune response to viral antigens
      and a high incidence of atherosclerosis. This study was initiated to evaluate the
      association between cytomegalovirus infection and atherosclerosis in patients
      with diabetes mellitus. Patients with diabetes mellitus type 1 and 2 (> 5 years)
      with (group A) and without (group B) clinical signs of atherosclerosis were
      included. Cytomegalovirus cultures were obtained, serum was screened for CMV
      antibodies and CMV-IgG and CMV-IgM titers were determined. Cytomegalovirus
      antibodies were detected more often in diabetic patients with atherosclerosis
      compared to patients without atherosclerosis (70.7 vs. 45.2%, P = 0.018. In
      female patients the prevalence of CMV-antibodies was 89.5 vs. 40.0% (P = 0.0037).
      CMV IgG titers were twice as high in group A compared to group B. Cytomegalovirus
      was cultured from four urine samples and two throat swabs in group B and in one
      urine and one throat swab in group A. The prevalence of cytomegalovirus
      antibodies was higher in diabetic patients with atherosclerosis compared to
      diabetic patients without atherosclerosis. This difference was most striking in
      the female population. CMV-IgG titers were twice as high in the atherosclerosis
      group. These data suggest that cytomegalovirus may play a role in the development
      of clinical atherosclerosis in patients with diabetes mellitus.

PMID- 9187416
TI  - Effect of smoking on the prevalence of albuminuria in Japanese men with non
      insulin-dependent diabetes mellitus.
AB  - Smoking is a risk factor for diabetic nephropathy in patients with IDDM and
      potentially those with NIDDM. We investigated the relationship between renal
      involvement and cigarette smoking in 148 men with NIDDM. The presence of renal
      involvement was assessed by determining the overnight urinary albumin/creatinine
      ratio (mg/g, ACR). The patients were divided into three groups, normo-, micro-,
      and macroalbuminuria, based on the ACR (< 30, 30-300, and 300 < or = mg/g,
      respectively). The incidence of micro-/macroalbuminuria in 81 smokers was
      significantly higher than that in 21 ex-smokers (stopped smoking at least 10
      years prior to the study) or 40 non-smokers (53.1, 33.3, and 20.0%,
      respectively). The prevalence of smoking in the groups of patients with normo-,
      micro-, and macroalbuminuria were 45, 73, and 76%, respectively. The relative
      risk (odds ratio) for the prevalence of micro-/macroalbuminuria associated with
      smoking was 4.5 (95% CI, 1.9-11.6, P < 0.001) in smokers and was 2.0 (not
      significant) in ex-smokers. Our results indicate that stricter counselling about
      the importance of quitting smoking will be necessary in patients with NIDDM to
      protect against the development of diabetic nephropathy.

PMID- 9187417
TI  - Anatomical architecture and electrical activity of the heart.
AB  - In most early studies of cardiac electrophysiology, the correlation between
      propagation of excitation and the architecture of cardiac fibers was not
      addressed. More recently, it has become apparent that the spread of excitation,
      the sequence of recovery, the associated time-varying potential distributions and
      the intra- and extracardiac electrocardiograms are strongly affected by the
      complex orientation of myocardial fibers. This article is a review of older and
      very recent, partly unpublished, mathematical simulations and experimental
      findings that document the relationships between cardiac electrophysiology and
      fiber structure. Important anatomical factors that affect propagation and
      recovery are: the elongated shape of myocardial fibers which is the basis for
      electrical anisotropy; the epi-endocardial rotation of fiber direction in the
      ventricular walls; the epi-endocardial obliqueness of the fibers ("imbrication
      angle"), and the conduction system. Due to the complex architecture of the
      fibers, many different pathways are available to an excitation wavefront as it
      spreads from a pacing site: the straight line; the multiple, bent pathways
      resulting from the epi-endocardial rotation of fiber direction; the coiling
      intramural pathways associated with the "imbrication" angles (Streeter) and the
      pathways involving the Purkinje network. Only in a few cases is the straight line
      the fastest pathway. The shape of an excitation wavefront at a given time instant
      results from the competition between all possible pathways. To compute the
      potential distributions and ECG waveforms generated by a spreading excitation
      wave we must know the successive shapes and positions of the wavefront, the
      architecture of the fibers through which it propagates and the spatial
      distribution of their anisotropic electrical properties.

PMID- 9187418
TI  - Time course of serum lipids and apolipoproteins after acute myocardial
      infarction: modification by pravastatin.
AB  - Pravastatin was administered to patients suffering an acute myocardial infarction
      starting with a dose of 10 mg/day at day 3 and continuing with a dose of 20
      mg/day up to a period of 3 months. The study was performed on the basis of a
      randomized placebo-controlled double-blind trial. At the dosage used pravastatin
      significantly lowered the total cholesterol and LDL-cholesterol levels and
      increased the HDL-cholesterol levels compared to placebo. A prospective clinical
      trial in order to examine the possible clinical relevance of these findings is
      recommended.

PMID- 9187419
TI  - Obstructive hypertrophic cardiomyopathy in type III glycogen-storage disease.
AB  - We present here a rare case of a patient affected by hypertrophic obstructive
      cardiomyopathy related to type III glycogenosis. In this patient the correct
      diagnosis could only be performed by endomyocardial biopsy.

PMID- 9187420
TI  - One and a half decades of the Lugano International Conference on Malignant
      Lymphoma: variations on a theme or true progress?

PMID- 9187422
TI  - The treatment of pediatric lymphomas: paradigms to plagiarize?
AB  - The excellent results in pediatric lymphomas presented at the Sixth International
      Conference on Malignant Lymphoma in Lugano encompass several emerging themes and
      provide paradigms which it may be possible to extrapolate to at least some adult
      lymphomas. In pediatric Hodgkin's disease, there is mounting evidence that
      radiation adds nothing except toxicity to effective chemotherapy regimens, with
      the possible exception that patients with bulky disease, particularly in the
      mediastinum, may benefit from involved-field radiation. This is of particular
      importance in view of the recently recognized high rate of late-occurring second
      solid tumors and cardiac infarction, largely referable to radiotherapy. It is
      likely that there will be greater efforts to eliminate radiation from treatment
      protocols wherever possible. In pediatric non-Hodgkin's lymphomas, the intensive
      regimens used by several cooperative groups in Europe and the United States have
      resulted in very high event-free survival rates--90% in B-cell lymphomas, and
      only slightly lower in T-cell lymphomas. These results stand in striking contrast
      to those obtained in adults with the same diseases, except those treated with the
      same treatment protocols, who appear to have a similar prognosis. Finally,
      progress in the characterization of the molecular abnormalities and viral
      association of pediatric lymphomas is leading to new approaches to diagnosis and
      the detection of minimal residual disease, as well as to the development of
      targeted treatment approaches.

PMID- 9187423
TI  - Treatment of childhood Hodgkin's disease without radiotherapy.
AB  - BACKGROUND: To minimize the side effects of treatment in children with Hodgkin
      disease (HD), chemotherapy was given without radiotherapy. PATIENTS AND METHODS:
      From 1975 to 1984, 21 patients with HD having lymph nodes < 4 cm were treated
      with six MOPP courses. From 1984 to 1987, all children presenting with HD (n =
      17) were given six ABVD courses. From 1987 to 1993 all children (n = 21) were
      treated with six alternating ABVD and MOPP courses. RESULTS: MOPP-treated
      children showed an event-free survival (EFS) of 91%, overall survival, 100%; ABVD
      treated children had an EFS of 70%, overall survival, 94%; ABVD-MOPP-treated
      children had an EFS of 91% and an overall survival of 91%. Two cases developed a
      second malignancy. Toxicity was low. CONCLUSIONS: In children, ABVD-MOPP
      treatment gives a good survival, and toxicity is low. Radiotherapy is not needed
      to treat HD in children.

PMID- 9187424
TI  - Long-term pulmonary sequelae after treatment of childhood Hodgkin's disease.
AB  - BACKGROUND: Pulmonary sequelae have been reported in patients treated for
      Hodgkin's disease (HD). Few data are available about patients treated for
      childhood HD followed over several years. PATIENTS AND METHODS: In a cross
      sectional study carried out for 76 months (median time) after treatment
      completion, we evaluated the lung function abnormalities and respiratory symptoms
      in 27 patients (16 males and 11 females) with HD diagnosed between 1983 and 1994
      (median age at diagnosis 11 years, range 2-16 years). They had been treated with
      chemotherapy and radiotherapy according to current protocol AIEOP-MH 83 (n = 14)
      or AIEOP-MH 89 (n = 13). At the time of the study, 26 patients were in first
      complete remission and one in second remission. Of the 27 patients, 19 had had
      mediastinal irradiation at a dose of 20 Gy (n = 5) or 20.8-44 Gy (n = 14). Forced
      vital capacity (FVC), functional residual capacity (FRC), forced expiratory
      volume in one second (FEV1), FEV1/FVC ratio, and maximal expiratory flow at 25%
      of FVC were registered; diffusion capacity for carbon monoxide (DLCO) was
      determined. Data were expressed as standard deviation (SD) score. Four patterns
      of respiratory function abnormalities were defined: restrictive, obstructive,
      isolated bronchiolar impairment, isolated diffusing impairment. RESULTS: Twelve
      patients (44%) were asymptomatic and showed completely normal pulmonary function
      tests. Three patients reported dyspnea on exertion, and one of them also cough
      and phelgm: out of these symptomatic subjects, only 1 had functional abnormality
      (isolated DLCO impairment). A restrictive pattern was found in 5 patients (18%),
      including 2 who also had a pathological DLCO SD score. Eight additional patients
      (30%) had isolated diffusing impairment. Oxygen saturation was normal in all
      patients. Forty-seven percent of patients with normal DLCO had had lower dose
      irradiation (20 Gy) compared to 10% of patients with impaired DLCO (P = 0.054).
      Similarly, patients with normal DLCO had had significantly less chemotherapy as
      compared to patients with abnormal DLCO (P = 0.003). Occurrence of lung
      abnormalities was not significantly associated with sex, age at treatment,
      mediastinal irradiation, and time elapsed from treatment completion. CONCLUSION:
      Adolescents and young adults treated for childhood HD are at risk for lung
      function abnormalities, significantly more frequent in patients who received more
      intense treatment, as mediastinal irradiation at a higher dose (> 20 Gy) and more
      chemotherapy blocks. Long-term follow-up should be offered to these patients
      because of their possible limited potential for pulmonary function and possible
      lesser resistance to adverse agents such as smoke, pollution, infections and
      aging.

PMID- 9187425
TI  - Effects of phosphodiester and phosphorothioate antisense oligodeoxynucleotides on
      cell lines which overexpress c-myc: implications for the treatment of Burkitt's
      lymphoma.
AB  - The product of the c-myc proto-oncogene is a highly conserved nuclear
      phosphoprotein whose expression is closely linked to cellular proliferation and
      differentiation. We have been interested in developing an antisense
      oligodeoxynucleotide (ODN) strategy to inhibit the proliferation of c-myc
      dependent malignancies for use in future specific therapies and bone marrow
      purging regimens. Our experimental approach was to incubate either antisense or
      sense ODNs, spanning the 5' cap region of the c-myc gene, with c-myc
      overexpressing cell lines (HL-60) Raji, MJBL, CA-46) for up to seven days.
      Proliferation assay to test the inhibitory effect of an unmodified antisense ODN
      15-mer (GCACAGCTCGGGGGT) showed that concentrations as low as 50 micrograms/ml
      significantly decreased proliferation of HL-60 cells by approximately 40% (P <
      0.0001; n = 6) compared to controls. Clonogenic assays showed that the same
      antisense ODN inhibited colony formation by MJBL (40%0 and Raji (52%) cells.
      Subsequent experiments to study the effect of a more nuclease-stable,
      phosphorothioate-modified antisense ODN 18-mer (GCAGCACAGCTCGGGGGT) revealed 66%
      inhibition of HL-60 cell proliferation at 96 and 120 hours at 50 micrograms/ml,
      whereas sense ODN control had no effect. However, tenfold less of the modified
      antisense ODN (1 micrograms/ml) was required to inhibit proliferation of HL-60
      cells by 50% compared to the unmodified antisense ODN. A decrease in the HL-60
      native c-myc protein level was also observed with 100 micrograms/ml of modified
      antisense ODN, but not with the sense ODN control, by immunoblot analysis.
      Additionally, concentrations up to 10 micrograms/ml of either modified antisense
      or sense ODN did not decrease CFU-GM formation (145 +/- 35%, P = 0.27) in human
      bone marrow, suggesting that these levels of ODN would have a negligible effect
      on normal hematopoietic cells. These pilot data suggest that modified antisense
      ODN directed at the cap region of the c-myc gene could specifically inhibit c-myc
      expression at a single, lower dose than unmodified ODN and may play a future role
      in inhibiting the growth of c-myc-dependent malignant cells.

PMID- 9187426
TI  - Application of long PCR to detect t(8;14)(q24;q32) translocations in childhood
      Burkitt's lymphoma and B-ALL.
AB  - BACKGROUND: Burkitt's lymphoma (BL) and B-ALL are characterized by chromosomal
      translocations juxtaposing the c-myc gene on chromosome 8 to one of the
      immunoglobulin loci. Translocations involving the immunoglobulin heavy chain
      (IgH) on chromosome 14 are found in approximately 75%-90% of these tumors. The
      breakpoint regions are located over a wide range on both chromosomes. PATIENTS
      AND METHODS: To detect the translocations, we developed a PCR method to generate
      long products. After extraction of genomic DNA (QiaAmp System, Qiagen, Hilden,
      Germany), DNA was amplified using a mixture of Taq and Pwo polymerases
      (Boehringer Mannheim, Germany). Several primer pairs from the S mu, JH, CH1 and
      the C alpha regions on IgH and from exon 1 and intron 1 of the c-myc gene were
      tested in each patient. RESULTS: Lymphoma cells from 20 children with Burkitt's
      lymphoma and B-ALL characterized by FAB-L3 morphology were examined. In 11/20
      patients, recombinations between chromosomes 8 and 14 could be detected with our
      primer pairs. PCR products from 800 to 3700 bp in length were obtained
      reproducibly. After amplification, the products were characterized by restriction
      enzyme digestion, hybridization, and in part by direct sequencing. CONCLUSIONS:
      This PCR-based method will allow us (1) to determine the localization of
      chromosomal breakpoints in primary tumor material, (2) to investigate whether
      distinct breakpoints are associated with treatment outcome, and (3) to detect the
      presence of minimal residual tumor cells during or after therapy.

PMID- 9187428
TI  - Can we improve upon the International Index?
AB  - The heterogeneity in outcomes in aggressive non-Hodgkin's lymphoma has prompted
      the development of clinical prognostic factor models which identify patients with
      different likelihoods of being cured of their disease. However, these clinical
      prognostic factor models are based on clinical features that are, in large part,
      surrogate variables for the biological heterogeneity of the disease. This review
      summarizes the development of clinical prognostic factor models and discusses
      some of the more recently described cellular and molecular features that may
      contribute to the biologic heterogeneity of aggressive NHL.

PMID- 9187427
TI  - Use of an anti-ALK antibody in the characterization of anaplastic large-cell
      lymphoma of childhood.
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase inappropriately
      expressed in lymphoid tissue involved by CD30+ anaplastic large-cell lymphoma
      (ALCL) with the translocation t(2;5)(p23;q35)(, which juxtaposes the
      nucleophosmin gene (NPM) with that encoding ALK, resulting in a hybrid (NPM-ALK)
      message. PATIENTS AND METHODS: A polyclonal antibody against residues of the
      kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical
      utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL)
      and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase
      method. RESULTS: Nineteen of 20 CD30+ cases (the majority exhibiting anaplastic
      morphology) labeled with anti-ALK 11, and 5/28 CD30- cases were also ALK+ (3 T
      cells, 1 null cell, and 1 B cell). Sixteen of 17 B-cell pediatric LCLs were
      negative, as were 6/6 cases of Hodgkin's disease and 7/7 cases of adult B-cell
      lymphoma. In pediatric LCLs with adequate follow-up (24/44 ALK+), there was no
      significant association between ALK expression and two-year event-free survival,
      similar to the finding reported previously for CD30 expression in these cases.
      CONCLUSION: We conclude that the majority of pediatric CD30+ ALCLs show ALK
      overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK
      fusion, but that the clinical significance of this entity remains unproven.

PMID- 9187429
TI  - Is the International Prognostic Index for aggressive lymphomas useful for low
      grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS
      Group, France.
AB  - BACKGROUND: The International Prognostic Index (IPI) is widely used to predict
      outcome of patients with aggressive lymphomas. Our goal was to assess the
      prognostic value of this index for low-grade lymphoma. PATIENTS AND METHODS: One
      hundred eighty-two patients with disseminated (stage III or IV) low-grade
      lymphoma were enrolled in a prospective multicenter trial. According to the
      initial features, treatment either was started immediately or was deferred until
      indicated by disease progression. Patients received the same polychemotherapy
      regimen, given monthly for six cycles. They were assigned to one of four risk
      groups according to the number of presenting risk factors: low-risk (0 or 1), low
      intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4). RESULTS:
      Survival curves (Kaplan-Meier method) demonstrated a high significant difference
      for the four groups (log-rank: P < 0.0001). Median survival for the low-risk
      group has yet to be reached, while that for the three other groups are,
      respectively, 65, 34, and 12 months. CONCLUSIONS: In this study, the IPI has been
      found to be an important prognostic tool in low-grade lymphoma and may be used in
      the selection of appropriate therapeutic approaches for individual patients.

PMID- 9187430
TI  - Comparison of gallium scan, computed tomography, and magnetic resonance in
      patients with mediastinal Hodgkin's disease.
AB  - BACKGROUND: In patients with Hodgkin's disease, the use of gallium-67
      scintigraphy (Ga-67) compared to conventional staging and restaging techniques is
      still controversial. In particular, in a combined modality treatment with
      chemotherapy and radiotherapy given in sequence, its role in detecting active
      disease after chemotherapy may be useful in planning the subsequent
      radiotherapeutic strategy. PATIENTS AND METHODS: From March 1990 to September
      1994, 125 patients with previously untreated histologically proven Hodgkin's
      disease were enrolled in two different prospective trials according to clinical
      stage. Staging procedures included Ga-67, chest-abdominal computed tomography
      (CT), and/or magnetic resonance (MR). All three tests were performed in 53
      patients at staging and in 47 at restaging. Results of Ga-67 at staging were
      compared to conventional procedures or pathological findings. Results of Ga-67,
      CT scan, and MR at restaging were compared to disease outcome during the follow
      up. Finally a cost/benefit ratio for each test was determined. RESULTS: At
      staging, Ga-67 showed lower sensitivity than CT and MR (90 vs. 96 and 100%,
      respectively) because of the number of false-negative images. Nevertheless, by
      using both CT and Ga-67 scan, the sensitivity is equal to that observed with MR
      (100%). At restaging, Ga-67 is superior to CT scan and equivalent to MR in
      detecting true negative patients (specificity: 98% vs. 45% vs. 92%). CONCLUSIONS:
      As a single technique, Ga-67 scan cannot substitute for CT scan or MR in staging
      patients with Hodgkin's disease. Nevertheless, Ga-67 scan has an important role
      in defining complete remission after treatment and therefore in planning
      subsequent treatment. Considering the lower costs of CT scan plus Ga-67 ($320)
      versus MR alone ($810), the two tests may be considered procedures of choice in
      staging as well as in restaging patients with Hodgkin's disease.

PMID- 9187431
TI  - Whole-body positron emission tomography (PET) for diagnosis of residual mass in
      patients with lymphoma.
AB  - BACKGROUND: PET using 18fluorodesoxyglucose (FDG) may offer the possibility of
      differentiating vital from necrotic residual masses. PATIENTS AND METHODS:
      Seventeen patients with HD and 17 patients with NHL underwent FDG-PET following
      therapy. According to staging by routine methods at diagnosis, 7 patients
      presented stage I, 13 stage II, 5 stage III, and 9 stage IV. A dose of 250-400
      MBq FDG was injected and whole-body PET was performed 30-60 minutes later.
      RESULTS: Residual mass was found in 32 patients with routine methods. FDG-PET was
      negative in 17 patients, who were considered to be in CR. None of them relapsed
      (median follow-up 63 weeks ). FDG-PET was positive in 17 patients. Sixteen
      patients had residual mass with routine methods. Four patients received radiation
      after PET. Their median follow-up is 58 weeks without relapse. Two other patients
      with lasting CR had FDG uptake outside the residual mass--one with confirmed
      pneumonia. Five patients had histologically confirmed lymphoma, 2 patients
      relapsed according to routine methods. One patient is likely to be false positive
      because of fracture at lymphoma site. Seven of 10 patients with FDG uptake in the
      residual mass after completed therapy relapsed. According to routine restaging, 2
      patients achieved CR. In 1 patient an additional focus was found in the humerus
      in spite of normal scintigraphy with histologically confirmed lymphoma. There
      were no false-negative results, but 3 false-positive results inside and 2 false
      positive results outside the residual mass after completed therapy. CONCLUSIONS:
      PET performed for evaluation of residual mass after treatment of lymphoma has a
      high predictive value.

PMID- 9187432
TI  - Is CHOP the standard of therapy for poor-prognosis large-cell lymphoma?

PMID- 9187433
TI  - Impact of high-dose salvage therapy (BEAM) on overall survival in younger
      patients with advanced large-cell lymphomas entered into BNLI trials.
AB  - The survival of two cohorts of patients with stage III/IV large-cell lymphomas
      treated by CHOP has been compared. In the first cohort of 88 patients (1974
      1982), high-dose therapy with autologous bone marrow transplantation (ABMT) was
      not available as salvage therapy and in the second cohort of 87 patients (1987
      1992), this was the recommended salvage for patients with disease that was still
      chemosensitive to conventional-dose therapy. The actuarial overall survivals at
      five years were 40% and 44% in the first and second cohorts, respectively,
      indicating that the availability of ABMT had made little impact. Of the 62
      patients in the second cohort who failed CHOP therapy, 8 died before second-line
      chemotherapy could be given, 1 refused more therapy, and 8 were considered
      unsuitable for further combination chemotherapy. Seven patients with localized
      disease remaining received local radiotherapy. Of the 38 patients given salvage
      therapy, 14 had chemoresistant disease. Only 9 patients received high-dose BEAM
      chemotherapy and ABMT, and 7 remain disease-free. ABMT was restricted to a highly
      select patient group, and as a result more widespread application of this
      strategy might result in only a modest further improvement.

PMID- 9187434
TI  - Persistent improved results after adding vincristine and bleomycin to a
      cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III
      IV intermediate- and high-grade non-Hodgkin's lymphoma. The EORTC Lymphoma
      Cooperative Group.
AB  - CHOP has been and still is regarded by many as the 'standard' treatment of
      advanced non-Hodgkin's lymphoma. In 1980 the EORTC Lymphoma Cooperative Group
      started a study to evaluate the addition of vincristine and bleomycin to its
      standard four-drug combination chemotherapy, CHVmP (cyclophosphamide,
      hydroxorubicin, Vm-26, prednisone). Eligible patients were stage III or IV,
      intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation E-I). One
      hundred-eighty-nine patients were entered, of whom 140 were eligible and
      evaluable. A previous report showed an improved response rate and failure-free
      survival (FFS) and overall survival for the combination CHVmP-VB. At ten years,
      the outcome still favors the addition of vincristine and bleomycin. The FFS was
      34% vs. 23% and the overall survival 34% vs 22%. This difference was mainly due
      to a difference in CR rate (74% vs. 49%), Relapse-free survival for patients
      reaching a CR was the same in both arms. When the patients were grouped according
      to the International Prognostic Factor Index, no statistically significant
      difference could be observed in favor of one treatment within either group. This
      trial clearly demonstrates the benefit gained by the addition of vincristine and
      bleomycin to 'standard' chemotherapy for intermediate and high-grade non
      Hodgkin's lymphoma.

PMID- 9187437
TI  - Report of the symposium on Cutaneous Lymphomas: Sixth International Conference on
      Malignant Lymphoma.
AB  - The symposium discussed the pathobiology, classification, and treatment of
      cutaneous lymphomas. Drs. Burg and Kadin commented on the pathophysiology of
      mycosis fungoides/Sezary syndrome and cutaneous CD30+ lymphoproliferative
      disorders, respectively. A proposed classification of primary cutaneous lymphomas
      from the EORTC was presented by Drs. Kerl and Sterry. Dr. Jaffe presented a
      classification of cutaneous lymphomas based on the REAL classification. All
      speakers agreed that primary cutaneous lymphomas are usually distinctive in their
      clinical behavior and biology, and differ from their nodal counterparts. The
      symposium concluded with remarks from Drs. Vonderheid and Hoppe on the
      therapeutic approach to primary cutaneous lymphoid malignancies.

PMID- 9187436
TI  - Eighty-one percent event-free survival in advanced Burkitt's lymphoma/leukemia:
      no differences in outcome between pediatric and adult patients treated with the
      same intensive pediatric protocol.
AB  - BACKGROUND: Advanced Burkitt's lymphoma (BL) has an extremely poor prognosis in
      adults. With a previous protocol including CNS prophylaxis, 40% of our adult
      patients achieved CR and only 13% became long survivors. In 1988, following this
      poor experience, we adopted a very intensive pediatric-derived protocol. PATIENTS
      AND METHODS: Twenty-one consecutive patients, 8 adults (median age 35, stage III:
      1; IV: 7; leukemias: 6) and 13 children (median age 10, state III: 8; IV: 5;
      leukemias: 4) were treated with the same protocol (POG 8617), based on alternate
      two-phase cycles with sequential high-dose CTX, VCR, ADM + CNS chemoprophylaxis
      (phase A) and HD MTX + HiDAC (phase B). Adults received 6 cycles, children 8;
      i.t. prophylaxis in phase B was omitted in adults. RESULTS: Twenty of 21 (95%)
      patients achieved CR (adults 100%, children 92%). Two patients died early; 2
      relapsed at 4 and 9 months. With a median follow-up of 28 months (4-96), 17
      patients (81%) are event free (adults 75%, children 85%). Severe infections
      affected 62% of adults and 15% of children. CONCLUSIONS: (1) The prognosis of
      adult advanced BL definitely improved with this intensive protocol. (2) There
      were no differences in outcome between adults and children. (3) Outcome of
      lymphoma and leukemia was similar. (4) Severe infections occurred frequently in
      adults. This intensive pediatric protocol requires a careful supportive therapy.

PMID- 9187435
TI  - Long-term survival advantage of MACOP-B over CHOP in intermediate-grade non
      Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group.
AB  - BACKGROUND: The initial publication of the results of the Australian and New
      Zealand Lymphoma Group (ANZLG) randomized controlled trial comparing MACOP-B and
      CHOP in patients with intermediate-grade non-Hodgkin's lymphoma (NHL) showed
      equivalent complete response rates, time to treatment failure, and survival. Here
      we report the long-term follow-up of the 236 patients entered on that study to
      determine if there were any long-term advantages or disadvantages associated with
      MACOP-B. PATIENTS AND METHODS: Two hundred thirty-six eligible patients were
      randomized between October 1986 and June 1991. The median duration of follow-up
      has been extended from 3.2 years in our previous publication to 6.5 years.
      RESULTS: As previously reported, the complete response (CR) rate for MACOP-B and
      CHOP chemotherapy was 51% and 59%, respectively. The estimated failure-free
      survival rate for MACOP-B and CHOP patients was 42% and 30%, respectively, at 5
      years (P = 0.045) and 37% and 25%, respectively, at 8 year (P = 0.057). The
      estimated overall survival rate at 5 years was 54% for MACOP-B and 41% for CHOP
      patients (P = 0.035) and at 8 years was 45% and 36%, respectively (P = 0.16).
      CONCLUSION: With this extended follow-up, we have shown a long-term survival
      advantage for MACOP-B chemotherapy over standard CHOP in patients with
      intermediate-grade non-Hodgkin's lymphoma.

PMID- 9187439
TI  - Follicular lymphoma: grounds for optimism.
AB  - The fact that follicular lymphoma is characterized by a specific immune phenotype
      and a nonrandom chromosomal translocation which may be detected at the molecular
      level makes it possible to design novel therapeutic strategies for curative
      therapy. Molecular markers may be used to test hypotheses. Some current causes
      for optimism are reviewed.

PMID- 9187438
TI  - Primary lymphoma of the stomach: three-year results of a prospective multicenter
      study. The German Multicenter Study Group on GI-NHL.
AB  - BACKGROUND: In October 1992, an ongoing prospective study on primary
      gastrointestinal (GI) lymphoma was initiated to evaluate histological features,
      sites of involvement, and management. PATIENTS AND METHODS: Until May 1996, 352
      patients were enrolled, with 279 being evaluable for clinical features (208
      patients presented with primary gastric lymphoma). Standardized diagnostic workup
      included central histologic review and endoscopic and radiologic evaluation of
      the complete GI tract. Primary surgery or conservative management depended on the
      physician's decision, followed by radiotherapy with or without chemotherapy.
      Treatment outcome is evaluable in 122 patients with gastric lymphoma. RESULTS: In
      279 evaluable patients, the distribution of NHL was as follows: stomach 74.6%,
      small bowel 8.6%, ileocoecal region 6.5%, multilocal GI involvement 6.8%. In
      gastric lymphoma, low-grade NHLs accounted for 39%. Of the remaining high-grade
      NHLs, 36.1% showed simultaneous low-grade components, thus being also of MALT
      origin. Of 208 patients with gastric NHL, 71.1% were classified as stage I and
      II1. CCR rate in stomach lymphoma is significantly higher compared to those of
      the small bowel, whereas involvement of multiple GI organs has the worst
      prognosis. So far only 7 patients with gastric NHL in stages I and II presented
      with progressive disease or relapse. Over all stages there seems to be no
      difference in therapeutic outcome in surgically or conservatively treated
      patients. Even after R0-resection in limited stages patients appear to have no
      better outcome. CONCLUSION: The value of surgery in treatment of primary gastric
      lymphoma--as favored by most authors--should be reexamined.

PMID- 9187440
TI  - B-cell chronic lymphocytic leukemia: recent progress in biology, diagnosis, and
      therapy.
AB  - B-cell chronic lymphocytic leukemia (CLL) is a highly common form of leukemia
      characterized by the accumulation of long-lived, functionally inactive, mature
      appearing neoplastic B lymphocytes. In addition, immune disturbances such as
      hypogammaglobulinemia and autoimmune phenomena (particularly, autoimmune
      hemolytic anemia) are frequently found in CLL patients [1-2]. The etiology of CLL
      is unknown. In contrast with other leukemias, there is no relationship between
      CLL and exposure to radiation or other cytotoxic agents. A genetic basis is
      highly likely since there are differences in the incidence of CLL in different
      countries (e.g., CLL accounts for 30%-40% of all the leukemias in Western
      countries as compared to 5%-10% in Asian countries) and the risk of contracting
      CLL is higher among persons with first-degree relatives with the disease [3].
      Because the incidence of CLL increases with age and the longer life expectancy of
      the general population, the age of patients at diagnosis is increasing. The
      median age at diagnosis is now about 70 years, with only one-third of the
      patients being less than 60 years of age. In the majority of the series, males
      predominate over females in a proportion of 1.5/1. The prognosis of patients with
      CLL is variable. However, clinical stages and other prognostic factors allow the
      individual risk of each patient to be assessed very accurately, which is useful
      for making treatment decisions. In the past two decades, significant progress has
      been made in CLL [4-10]. This review summarizes recent advances in the biology,
      diagnosis, and therapy of CLL.

PMID- 9187441
TI  - Treatment of mantle-cell lymphomas with the VAD +/- chlorambucil regimen with or
      without subsequent high-dose therapy and peripheral blood stem-cell
      transplantation.
AB  - BACKGROUND: MCL is a well-described clinicobiological entity that presents the
      worst prognosis of the small-cell lymphomas. No treatment is known as the
      reference treatment. On the basis, first, of clinicobiological similarities
      between MCLs and multiple myelomas and, second, of our experience of chlorambucil
      in high intermittent dose in MCLs, we have treated MCL with the VAD regimen both
      with and without chlorambucil. PATIENTS AND METHODS: Thirty disseminated MCL
      patients from three institutions, most in relapse (70%), were treated with the
      classical VAD regimen: 4 weeks VAD for 12 patients and VAD with 12 mg
      chlorambucil (d20-d29) for 5 weeks (VAD+C) for 18 patients. Five patients
      received complementary high-dose therapy (Alkeran or cyclophosphamide HD with
      TBI) and peripheral blood stem-cell transplantation. RESULTS: Complete response
      was achieved in 43% of the patients in which 84.5% were treated by VAD+C. The
      median overall survival from the diagnosis was 52 months, and from the first VAD
      +/- C (OSvad) was 22.5 months, with a 20.5 month (0-75) median follow-up between
      diagnosis and the first VAD +/- C. The OSvad was significantly better for
      patients with fewer than two prognostic factors (ECOG, lymphocytosis, blastic
      variant, LDH level, and Ki-67 score). Four of five patients treated with HDT and
      PBSCT were alive in CR 12.5 months (7-22) after the first VAD +/- C regimen.
      CONCLUSION: The VAD regimen appears effective in disseminated MCL patients and
      even better when associated with chlorambucil. HDT and PBSCT appear promising in
      younger patients in CR before HDT. A multicenter prospective study is in
      preparation to confirm these encouraging results.

PMID- 9187442
TI  - Hepatitis B virus carriers in the treatment of malignant lymphoma: an
      epidemiological study in Japan.
AB  - BACKGROUND: Hepatitis B after the withdrawal of cytotoxic chemotherapy in
      hepatitis B virus (HBV) carriers is well known and may lead to fatal hepatic
      failure. We retrospectively analyzed the prevalence of HBV carriers, the
      incidence, and the risk factors of hepatitis B in the treatment of malignant
      lymphoma. PATIENTS AND METHODS: HBV carriers were defined as patients with
      positive HBs-antigen, either with normal or abnormal serum aminotransferase level
      at patient presentation. Questionnaires to the members of the Japan Lymphoma
      Treatment Study Group included general information, details about HBV carriers,
      and further information about hepatitis B. RESULTS: Among 1380 patients collected
      from eight institutions, 45 patients (3.26%) were determined to be HBV carriers,
      Hepatitis B developed in 17 of the HBV carrying patients (37.8%). Seven of those
      17 (41.2%) died of hepatic failure. Hepatitis developed at a high rate in
      patients who were negative for HBe-antigen (50%), and who had received second- or
      third-generation chemotherapy (63.2%). CONCLUSION: We confirmed that hepatitis B
      developed with high frequency in HBV carriers with malignant lymphoma. Moreover,
      hepatitis often resulted in fatal hepatic failure. It is necessary to prevent the
      hepatitis B developing in HBV carriers when receiving intensive chemotherapy for
      malignant lymphoma.

PMID- 9187443
TI  - Patients with stage III/IV Hodgkin's disease in partial remission after MOPP/ABV
      chemotherapy have excellent prognosis after additional involved-field
      radiotherapy: interim results from the ongoing EORTC-LCG and GPMC phase III
      trial. The EORTC Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie.
AB  - BACKGROUND: Failure to reach complete remission (CR) with chemotherapy in
      advanced stages of Hodgkin's disease is considered a poor prognostic factor for
      progression-free and overall survival. The role of radiotherapy after
      chemotherapy-induced remission is controversial. PATIENTS AND METHODS: In 1989,
      the EORTC/GPMC started a randomized phase III trial on involved-field RT (IF-RT)
      after MOPP/ABV hybrid-induced remission in patients with stage III/IV Hodgkin's
      disease. In this ongoing trial, patients in CR after chemotherapy are randomized
      between IF-RT and no further treatment. Patients in partial remission (PR) all
      receive IF-RT. Patients, age 15-70 years, with previously untreated stage III/IV
      Hodgkin's disease are eligible. The randomized treatment arms are still blinded.
      The interim analysis of May 1996 focuses on the outcome of patients in
      chemotherapy-induced PR. RESULTS: A total of 405 of 493 registered patients were
      evaluable for response to chemotherapy. Fifty-nine percent of patients attained a
      CR, 37% a PR, and only 4% failed to respond. The IF-RT was actually given to 90%
      of the PR patients. After a median follow-up of 43 months, the five year
      progression-free and overall survival for patients in PR was 75% and 87%,
      respectively. CONCLUSION: IF-RT after MOPP/ABV-induced partial remission in stage
      III/IV Hodgkin's disease produces excellent failure-free and overall survival.
      Early intensification of treatment of this group of patients is not indicated.

PMID- 9187444
TI  - Hodgkin's disease: complications of therapy and excess mortality.
AB  - BACKGROUND: The long-term survival of patients treated for Hodgkin's disease
      permits careful evaluation of long-term complications and excess mortality.
      PATIENTS AND METHODS: Between 1960 and 1995, 2498 patients who were treated for
      Hodgkin's disease at Stanford University were evaluated. Survival, freedom from
      relapse, and important complications of therapy (cardiac disease and secondary
      cancers) were analyzed, and risk of mortality from all causes was calculated
      utilizing absolute excess risk calculations. RESULTS: The risk of death from
      Hodgkin's disease is 17% at 15 years of follow-up and increases only slightly
      thereafter. The risk of death from other causes is also 17% at 15 years, but
      increases sharply thereafter. The major causes of mortality (other than Hodgkin's
      disease) are secondary cancers and cardiac disease. Second cancers with
      significant increase in risk include leukemia (acute nonlymphocytic), non
      Hodgkin's lymphoma, lung/pleural cancer, breast cancer, melanoma, soft tissue and
      bone sarcomas, stomach cancer, salivary gland tumors, thyroid cancer, and
      pancreatic cancer. The absolute excess risk of death from causes other than
      Hodgkin's disease increases during each five-year follow-up interval for at least
      25 years. However, the absolute excess risk of death during similar follow-up
      periods is less for patients treated in more recent years (1980-1995) than in the
      prior treatment era (1962-1980). CONCLUSIONS: Mortality for causes other than
      Hodgkin's disease is important in the long-term follow-up of patients. Causes of
      death are often treatment related. Changes in treatment programs can reduce the
      long-term excess risk of death from complications of therapy.

PMID- 9187445
TI  - New drugs in non-Hodgkin's lymphoma.
AB  - While novel agents designed to target molecular abnormalities involved in
      lymphoma pathogenesis are most likely to improve current therapeutic results,
      cytotoxic therapy remains the main-stay of therapy. Several new chemotherapy
      agents, including purine antimetabolites, taxanes, camptothecins, suramin, and
      protein kinase C inhibitors, are discussed. Other issues important in lymphoma
      drug development, including the limited patient population available for
      evaluation of investigational agents, are also considered.

PMID- 9187446
TI  - Paclitaxel (Taxol) for the treatment of lymphoma.
AB  - Paclitaxel (Taxol) was recently tested in patients with relapsed and refractory
      lymphoma in two phase II clinical trials using two different infusion schedules.
      The first, reported from the NCI (USA), used a 96-hour intravenous continuous
      infusion schedule, and the second, from our group, used a 3-hour infusion. In the
      NCI trial, 29 evaluable patients were treated with 140 mg/m2 every three weeks,
      which achieved a 17% response rate (all PRs); while we treated 96 evaluable
      patients with 200 mg/m/ every three weeks, which achieved a 25% response rate (10
      CRs and 14 PRs, 95% CI: 17%-35%). In our trial, patients with relapsed (not
      primary refractory) intermediate-grade lymphoma had a response rate of 50%, and
      those with relapsed low-grade lymphoma had a response rate of 31%. In a follow-up
      trial, 12 patients who failed to respond to 3-hour infusion of paclitaxel were
      crossed over to receive paclitaxel by 96-hour infusion. None of the 12 evaluable
      patients achieved a major clinical response. Similarly, of 25 patients treated
      with cyclosporine A and paclitaxel after failing therapy with single-agent
      paclitaxel, only one patient (4%) responded. We conclude that paclitaxel has a
      promising single-agent activity, most prominently in patients with relapsed
      intermediate-grade lymphoma. Paclitaxel-based combination programs are currently
      being evaluated in our institution.

PMID- 9187447
TI  - Radioimmunotherapy strategies for non-Hodgkin's lymphomas.
AB  - Radioimmunotherapy offers an exciting new therapeutic modality for patients with
      relapsed non-Hodgkin's lymphoma; however, considerable debate exists regarding
      the optimal dose and administration schedule for radioimmunoconjugates.
      Myelosuppression has been the dose-limiting toxicity of most clinical trials
      employing radiolabeled antibodies, and this complication has generated both high
      dose and low-dose treatment strategies. 'Low-dose' strategies are
      nonmyeloablative and rely upon repetitive infusions to effectively eradicate
      tumor masses. Trials incorporating low-dose radioimmunotherapy have documented
      high response rates, though the durability of these responses remains unclear.
      The most encouraging nonmyeloablative studies have documented objective responses
      in 70%-80% of patients, complete responses in 30%-50% of patients, minimal
      toxicity, and a median response duration of 12 months. In contrast, high-dose
      trials performed in conjunction with autologous hematopoietic stem cell
      transplantation have demonstrated objective responses in 95% of patients,
      complete responses in 85% of patients, with a progression-free survival of 62%
      and an overall survival of 93% with a median follow-up of two years. Toxicities
      are considerably higher than those reported with nonmyeloablative regimens, but
      are modest compared to conventional marrow transplant conditioning regimens
      incorporating total body irradiation (TBI). Ongoing trials integrating high-dose
      radioimmuotherapy with high-dose chemotherapy in an autologous transplantation
      setting are testing the hypothesis that targeted radiotherapy plus chemotherapy
      will provide increased efficacy and diminished toxicity as compared to
      nonspecific external beam TBI-containing regimens.

PMID- 9187448
TI  - The emerging role of immunotoxins in leukemia and lymphoma.
AB  - Despite important advances in conventional cancer therapy, there is still a
      strong need for new approaches in order to reduce cancer death rates, which have
      not been drastically influenced in the past ten years. Since minimal residual
      disease is regarded as the major cause for relapses of malignant diseases,
      immunotherapeutic strategies utilizing monoclonal antibodies (MoAbs) or their
      conjugates to target 'dormant' tumor cells have increasingly attracted scientific
      interest. Immunotoxins (ITs) constructed by chemically linking plant or bacterial
      toxins to a MoAb can selectively kill their target cells when internalized after
      binding to specific cell surface receptors. Many different ITs against various
      blood-borne as well as solid malignancies have been successfully tested in vitro
      and in animal models. Chemically linked ITs and recombinant fusion toxins
      generated by using DNA technologies are currently being evaluated for their
      antitumor activity in several clinical phase I/II/III trials. While serious side
      effects are rare, there are still many problems to be solved, such as the
      immunogenicity of the toxin and/or antibody moiety or the poor capacity of ITs to
      penetrate large solid tumors. At the moment only heavily pretreated patients with
      massive tumor burden are admitted to early clinical studies, so that even minor
      responses after IT treatment are encouraging. However, minimal residual disease
      is expected to be most amenable to IT therapy.

PMID- 9187449
TI  - Shall we be sucked in, washed up, and blown over by the changes in health care or
      make plans to reclaim the soul of health care?

PMID- 9187450
TI  - Resilience--a survival tool for the nineties.

PMID- 9187451
TI  - Preadmission testing.

PMID- 9187452
TI  - Surgical treatment of pheochromocytomas.
AB  - Pheochromocytomas are tumors that develop from chromaffin tissue of the embryonic
      sympathoadrenal system. These tumors may occur anywhere chromaffin tissue exists
      but most often develop in the adrenal medulla. Less than 50% of patients are
      diagnosed with pheochromocytomas while alive, and most of these tumors are found
      on autopsy. The classic signs and symptoms of pheochromocytomas are headache,
      perspiration, palpitations, pallor, and paroxysmal hypertension. Elevated levels
      of vanillylmandelic acid and metanephrines in patients' 24-hour urine collections
      are the most reliable diagnostic indicators of pheochromocytomas. Most patients
      with pheochromocytomas can be cured if diagnoses and surgical resections of
      tumors occur before irreversible cardiovascular disease and end-organ damage from
      hypertension develop.

PMID- 9187453
TI  - Perioperative nursing challenges for the Russian emigre nurse.
AB  - Three San Francisco organizations participated in an integration program that
      focused on the design, implementation, and evaluation of a unique training
      project that prepared Russian emigre nurses for employment in the US health care
      industry. The Russian Nurse Project is a unique program that affiliates emigre
      nurses with specific language and cultural skills and focuses on the increasing
      Russian immigrant patient population. The project's implementation and diversity
      strategies, as they pertain to the perioperative areas of nursing practice in
      this country, are described.

PMID- 9187454
TI  - Effect of surgical hand scrub time on subsequent bacterial growth.
AB  - In this experimental study, the researchers evaluated the effect of surgical hand
      scrub time on subsequent bacterial growth and assessed the effectiveness of the
      glove juice technique in a clinical setting. In a randomized crossover design, 25
      perioperative staff members scrubbed for two or three minutes in the first trial
      and vice versa in the second trial, after which the wore sterile surgical gloves
      for one hour under clinical conditions. The researchers then sampled the
      subjects' nondominant hands for bacterial growth, cultured aliquots from the
      sampling solution, and counted microorganisms. Scrubbing for three minutes
      produced lower mean log bacterial counts than scrubbing for two minutes. Although
      the mean bacterial count differed significantly (P = .02) between the two-minute
      and three-minute surgical hand scrub times, it fell below 0.5 log, which is the
      threshold for practical and clinical significance. This finding suggests that a
      two-minute surgical hand scrub is clinically as effective as a three-minute
      surgical had scrub. The glove juice technique demonstrated sensitivity and
      reliability in enumerating bacteria on the hands of perioperative staff members
      in a clinical setting.

PMID- 9187455
TI  - Key concepts in informed consent for perioperative nurses.

PMID- 9187456
TI  - An ethical examination of cloning.

PMID- 9187457
TI  - Safer use of glutaraldehyde.

PMID- 9187458
TI  - Nutritional supplements and surgical patients.
AB  - Surgical team members should be aware of which nutritional supplements may be
      harmful or helpful to surgical patients. Informed education of patients may
      prevent bleeding problems, wound-healing problems, prolonged hematomas, and
      dangerous immune system depletion.

PMID- 9187459
TI  - Legal and ethical considerations of informed consent.
AB  - The law of informed consent remains ineffective at resolving patient
      comprehension issues primarily because differing interpretations exist regarding
      who is responsible for the duty to inform. Court cases continue to set precedents
      for practicing physicians and other health care providers; however, other
      measures can be applied for effectual patient advocacy. Health care personnel
      should rewrite typical consent forms in simpler terms, use larger print, and
      create duplicate copies. If patients are given copies of the permits they sign,
      the can reread the forms at home when they are more comfortable. For true
      autonomy to exist in informed consent for surgical procedures, consent forms
      should contain patients' primary languages whenever possible, or an adequate
      interpreter should be made available. Surgeons, nurses, and other health care
      providers must become aware of their responsibilities related to informed consent
      for treatment. It is necessary for health care personnel to develop and use
      effective communication techniques and remember that although some patients are
      more visually attuned to new information, other patients may benefit more from
      listening or reading. The cases in this article show that a patient's autonomy is
      part of the informed consent process and the duty to inform the patient lies with
      the person performing the procedure. A more important issue, however, involves
      the patient's comprehension of the information given, because without it, the
      patient cannot achieve true autonomy in making decisions. Ensuring that all
      elements of informed consent are met to obtain informed consent will result in
      fewer malpractice claims, greater patient satisfaction, and an improved
      professional image. Nevertheless, nurses should make themselves aware of the
      state laws in which they practice, including their nurse practice acts. They then
      should advocate for patient rights by encompassing all elements of informed
      consent.

PMID- 9187460
TI  - An overview of statistical and clinical significance in nursing research.

PMID- 9187461
TI  - Former Governor Richard D. Lamm discusses changes in health care and their
      effects on perioperative nursing. Interview by Candace L. Romig.

PMID- 9187462
TI  - Effect of peritoneal fluid from patients with mild and severe endometriosis on
      endometrial stromal cell proliferation.
AB  - The aim of this study was to evaluate and compare the mitogenic effect of
      peritoneal fluid (PF) from women with mild and severe endometriosis on the
      endometrial stromal cell proliferation. Increasing concentrations of PF from
      women with and without mild or severe endometriosis were added to primary
      endometrial stromal cell cultures and 3H-thymidine incorporation was used to
      assess DNA synthesis in these cultures. PF from women with mild endometriosis
      induced a statistically significant dose-dependent increase in stromal cell
      thymidine uptake ranged from 5.8 to 14.5 fold, whereas PF from women with severe
      endometriosis produced an average 51% inhibition of stromal cell proliferation of
      compared with cells exposed to non-endometriosis PF or exposed to nutrient medium
      supplemented with 2.5% calf serum alone. PF samples from patients with stage I
      endometriosis induced a statistically dose-dependent increase in stromal cell
      proliferation, whereas PF from patients with stage IV endometriosis caused a
      significant inhibition.

PMID- 9187463
TI  - Serum CA 125 levels and survival in advanced ovarian cancer.
AB  - We made a retrospective analysis of 85 patients with elevated serum CA 125 after
      surgery for ovarian cancer. Absolute CA 125 serum levels were a poor guide to
      prognosis. However, the ratio between the serum CA 125 after the first, second,
      or third course of treatment and the postoperative value was an excellent guide
      to prognosis. These were also independent and stable in the Cox Regression
      analysis.

PMID- 9187464
TI  - Sperm count in ejaculates and after sperm selection with discontinuous percoll
      gradient centrifugation technique, as a prognostic index of IVF outcome.
AB  - Success of IVF with low sperm count will depend on the retrieval of the maximum
      number of normal motile sperms, and this makes the selection of an appropriate
      technique critical. Various in vitro methods have been developed for selecting
      human sperm cells. Sperm selection using percoll gradient has been reported to
      yield upto 60% motile and morphologically normal spermatozoa from a normal semen
      sample. In this study, we have attempted to determine a possible relationship
      between sperm count in ejaculates before and after selection with percoll
      gradient centrifugation on one hand, and fertilization, cleavage and pregnancy
      rates in an IVF program on the other. With increased sperm count at the time of
      IVF treatment using selected sperm, we observed higher fertilization, cleavage
      and gestational rates. In conclusion, sperm concentration before and after
      selection with percoll may be considered a prognostic parameter for the
      determination of fertilization potential and pregnancy rates in an IVF program.

PMID- 9187465
TI  - Pelvic exenteration for the treatment of gynecological malignancies.
AB  - Twenty-three patients undergoing pelvic exenteration for primary and recurrent
      gynecological malignancies from 1976 to 1994 are reported. Fifteen patients
      underwent total pelvic exenteration, 3 underwent anterior exenteration, and 5
      underwent a posterior procedure. Eight patients had exenteration as their primary
      treatment (primary group), and 15 underwent exenteration as secondary treatment
      (recurrent group). In the primary group, two patients developed recurrence and
      died of it at 6 and 20 months after operation. Five patients are still being
      followed up and are alive without disease. Four of these 5 patients have survived
      more than 5 years. In the recurrent group, 12 patients were followed up and three
      died of complications during the early years. Seven patients died of cancer with
      the mean survival time of 16.6 months. The mean age, average operating time, and
      mean blood loss in the primary and recurrent groups were 57 vs. 53 years, 8 hours
      and 20 min vs. 8 hours and 10 min, and 4,120 vs. 4,190 ml, respectively. The
      overall cumulative 5-year survival rate was 34.7%, being 68.6% in the primary
      group and 16.7% in the recurrent group. It is noteworthy that the 5-year survival
      rate was 51.3% in the patients who had surgical margins free of disease. In
      conclusion, pelvic exenteration should be considered an acceptable therapeutic
      option when appropriately selected.

PMID- 9187466
TI  - Umbilical cord androgens in infants of diabetic mothers.
AB  - The aim was to measure umbilical cord testosterone and androstenedione and to
      explore possible relationships with fetal weight and insulin levels.
      Testosterone, androstenedione and insulin were measured at birth in venous
      umbilical blood in 12 infants of gestational diabetic mothers and in 12 control
      subjects. The mean concentrations of umbilical testosterone and androstenedione
      were not significantly different between the infants of the diabetic and control
      mothers. No significant correlation was found between maternal weight, fetal
      weight or insulin concentrations and androgen levels.

PMID- 9187467
TI  - The influence of infant birth weight on post partum stress incontinence in obese
      women.
AB  - One hundred ninety four women with a Body Mass Index (BMI) of at least 30 kg/m2
      who were delivered vaginally between 01 10 93 and 30 09 95 at the obstetric
      department, Herning Central Hospital, were sent a postal questionnaire about
      stress incontinence. The response rate was 89.2%. In the heavy birth weight group
      (n = 4000 g or more) stress incontinence increased from 10.6% before pregnancy to
      34.0% post partum. In the low birth weight group 6.9% suffered from stress
      incontinence before pregnancy increasing to 30.6% post partum. There was no
      difference in the reporting of mixed or urge incontinence between the two groups.

PMID- 9187468
TI  - Survival and quality of life after percutaneous nephrostomy for malignant
      ureteric obstruction in patients with terminal cervical cancer.
AB  - We describe 24 consecutive patients with cervical cancer stage III or IV who
      received palliative urinary diversion by percutaneous nephrostomy. All patients
      had proven malignant ureteric obstruction, uremia and failed ureteric stenting.
      11 of 17 patients with extensive primary cancer and local lymph node involvement
      had an acceptable quality of life for 2 or more months while the mean survival
      was 5.6 months. Patients with disseminated metastasizing cancer were not
      satisfactorily served by nephrostomy.

PMID- 9187469
TI  - Quadruplet in vitro fertilization pregnancy complicated by fetal reduction and
      leiomyoma.
AB  - A woman had a quadruplet IVF pregnancy with a leiomyomatous uterus. Pregnancy
      resulted in the birth of one baby after missed abortion of one fetus and
      selective reduction of two others. The woman had a left deep calf vein thrombosis
      in the first half of pregnancy.

PMID- 9187470
TI  - Myoadenylate deaminase deficiency myopathy in pregnancy.

PMID- 9187471
TI  - Hypoxic and ischemic disorders of infants and children. Lecture for 38th meeting
      of Japanese Society of Child Neurology, Tokyo, Japan, July 1996.
AB  - Hypoxia-ischemia damages selected regions of the immature at different ages.
      Prior to 32 weeks gestation the periventricular white matter is selectively
      vulnerable but in the last trimester the basal ganglia become especially
      vulnerable to injury. Hypoxia-ischemia causes injury by activating a series of
      biochemical events that unfolds over a period of hours to days following the
      initial insult and we are investigating the ways in which age modifies these
      events. The cascade includes release of glutamate, overstimulation of excitatory
      amino acid receptors and raised intracellular levels of calcium. Clinically this
      series is manifested by hypoxic-ischemic encephalopathy (HIE), a syndrome that
      includes coma, seizures, a burst suppression EEG, respiratory depression and
      severe hypotonia. Clinical studies have established a relationship between the
      severity of neonatal encephalopathy and later manifestations of brain damage or
      cerebral palsy. Potential neuroprotective therapies need to be effective when
      given after the insult but the 'therapeutic time window' for most N-methyl-D
      aspartate (NMDA) glutamate antagonists is limited after injury. Using a model of
      hypoxic-ischemic injury and neonatal rats and hypothermic-circulatory arrest in
      dogs, we found that immunohistochemical staining for neuronal nitric oxide
      synthase (nNOS) is markedly increased from 6 to 24 h after the insult in the
      basal ganglia and cortex. The induction of nNOS preceded the time of maximal
      neuronal necrosis and during the time when many apoptotic nuclei were appearing.
      We have also found that a brief period of 2 h of mild hypothermia (32 degrees C)
      following hypoxia-ischemia in neonatal rats delayed neuronal necrosis by more
      than a week. We are determining whether this delay is related to a change in nNOS
      activation. Induction of nNOS in the post-insult period may contribute to
      expression of injury and signs of encephalopathy following a hypoxic-ischemic
      insult.

PMID- 9187472
TI  - Improvement of hypertonus after treatment for sleep disturbances in three
      patients with severe brain damage.
AB  - Treatment for sleep disturbance was given to three patients with severe brain
      damage (a 14-year-old boy, an 8-year-old girl and a 9-year-old boy), and changes
      in their muscle tone were estimated using F-wave analysis. In all patients, F
      wave analysis was performed in the ulnar nerve before and 2 weeks after treatment
      with flunitrazepam or melatonin. From 16 recordings of F-waves, the mean
      amplitude and latency, the ratio of F-wave amplitude to M-wave amplitude (F/M
      ratio), the mean F-wave conduction velocity and the F-wave occurrence were
      evaluated. All patients showed at least one significant decrement of mean F-wave
      amplitude, the F-wave occurrence and mean F/M ratio, which suggests a reduction
      in muscle tone after treatment for sleep disturbance. It is concluded that
      treatment for sleep disturbance occurring in brain damage is important in view of
      the improvement of increased muscle tone.

PMID- 9187473
TI  - MRI findings and sensorimotor development in infants with bilateral spastic
      cerebral palsy.
AB  - The correlation between MRI findings and sensorimotor development was
      investigated in a group of 48 infants with bilateral spastic cerebral palsy (CP).
      The ages at MRI examination and cognitive assessment were fairly homogeneous
      (mean 15 months and 17 months, respectively). The following MRI parameters were
      scored: size of lateral ventricles, extension of white matter lesions and of
      white matter reduction, thinning of corpus callosum, presence and size of cystic
      areas, dimension of subarachnoid spaces and presence of cortical abnormalities.
      Cognitive assessment included Griffiths Developmental Scales and Uzgiris-Hunt
      Scales. The patients were subdivided into six classes according to intellectual
      level (DSM-III-R). For the whole group a highly significant correlation was found
      between all MRI parameters and the level of cognitive development. This result
      was probably due to the inclusion of 14 untestable, severely mentally retarded
      infants, who showed very severe MRI abnormalities. However, when the untestable
      infants were excluded from the analysis, it was the presence of cysts and the
      entity of white matter reduction that correlated with both Griffiths Scales and
      Uzgiris-Hunt Scales. These results indicate the clinical value of MRI findings
      and particularly of white matter abnormalities for early identification of
      sensorimotor impairment in infants with bilateral spastic CP.

PMID- 9187474
TI  - Differential development of the human cerebellar vermis: immunohistochemical and
      morphometrical evaluation.
AB  - Differential development of regions of the human cerebellar vermis was evaluated
      immunohistochemically and morphometrically between 18 weeks of gestation and 10
      years of age. The density of Purkinje cells in the cerebellar vermis decreased
      rapidly until 38 weeks of gestation and slowly thereafter. At all stages of
      development, the density was higher in the posterior (lobules VI-IX) than the
      anterior vermis (lobules I-V). The area of cut sections of the anterior and
      posterior vermis in the mid-sagittal section increased rapidly before 40 weeks of
      gestation and gradually after birth, whereas growth was slower in the nodules.
      These developmental characteristics may be related to the selective
      susceptibility of cerebellar regions to environmental insults.

PMID- 9187475
TI  - Rett syndrome: geographic variation in prevalence in Norway.
AB  - The prevalence of Rett syndrome is reported for three Norwegian counties
      (Rogaland, Ostfold and Nordland). The total number of females between 3 and 19
      years of age in these counties was 96,920, and among these 21 females with Rett
      syndrome were identified, yielding a prevalence rate for Rett syndrome of 2.17
      per 10,000 girls. One reason for this comparatively high prevalence rate might be
      that the full spectrum of Rett syndrome variants was included. The quality of the
      health care system and the awareness of Rett syndrome and its variants among
      Norwegians physicians also make it unlikely that many case were missed. However,
      the high total prevalence was caused by a statistically significant larger number
      of girls with Rett syndrome in Rogaland than in the other two counties. Sixteen
      of the girls were identified in Rogaland county, which gives a prevalence rate
      for this county of 3.77 per 10,000 girls. The prevalence rates in the two other
      counties were 1.05 and 0.77 per 10,000 girls. The geographical distribution of
      girls with Rett syndrome in Rogaland is probably due to genetic clustering.
      Geographical mobility in Norway is limited and many families have lived in the
      same geographical area for generations. An explanation based on genetic
      clustering is also supported by the fact that several of the girls with Rett
      syndrome in Rogaland county are known to be related.

PMID- 9187476
TI  - Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C
      and vitamins B1 and B2.
AB  - The therapeutic efficacy of a regimen consisting of intravenous injection of
      Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine
      diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined
      therapy was applied to nine patients with MEM, including four with mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the
      standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and
      later by means of intermittent injections for maintenance treatment. Clinical
      improvement was obtained in eight of the patients. Improvement was observed in
      the muscle symptoms of easy fatigability, motor disability and severity of stroke
      like episodes, as well as in various other symptoms such as phosphate, tinnitus,
      headache, corneal edema, chilblains, thalamic pain, respiratory failure, and
      nystagmus. This clinical improvement was maintained for more than 1 year by
      additional intermittent injections. In conclusion, this therapy was fairly
      effective for the management of patients with MEM.

PMID- 9187477
TI  - L-2-Hydroxyglutaric aciduria: clinical, biochemical and magnetic resonance
      imaging in six Portuguese pediatric patients.
AB  - We present clinical, biochemical and cranial magnetic resonance imaging data of
      six pediatric patients with L-2-hydroxyglutaric aciduria. All the children have
      the same ethic origin and lived in the northern area of Portugal. Our findings
      reinforce the described phenotype of this rare metabolic disease with mental
      deficiency, severe cerebellar dysfunction, mild extrapyramidal and pyramidal
      symptoms, progressive macrocephaly and seizures. Magnetic resonance imaging
      revealed subcortical leukoencephalopathy, cerebellar atrophy and signal changes
      in the putamina and dentate nuclei. These were similar to those of the previous
      reports in all patients. The urinary excretion of L-2-hydroxyglutaric acid was
      variably increased in all patients. The other persistent biochemical abnormality
      was hyperlysinemia. We have found a strong correlation between the severity of
      the clinical manifestations and the extension of the lesions in the neuroimaging
      studies. There was no correlation between the clinical findings and the amount of
      urinary excretion of L-2-hydroxyglutaric acid. We report the second case in the
      literature of a cerebral thalamic tumor in L-2-hydroxyglutaric aciduria;
      neuropathological examination of the surgical biopsy demonstrated a diffuse
      fibrillary astrocytoma.

PMID- 9187478
TI  - The effectiveness of clonazepam on the Rolandic discharges.
AB  - Rolandic discharge (RD), noted in the electroencephalography (EEG) of patients
      with benign epilepsy in childhood with centrotemporal spikes (BECCT) has several
      unique features. One feature is that the amount or frequency of RDs does not
      correlate well with the incidence of seizures in BECCT although it is a key
      finding in the diagnosis of this epileptic syndrome. In this study, we examined
      the efficacy of antiepileptic drugs focusing on the disappearance of RDs in
      relationship with seizure control. Forty patients with BECCT who were not
      medically treated prior to this study were randomly sorted into three groups.
      Twenty patients were assigned for clonazepam (CZP) treatment, 10 patients for
      valproate (VPA) and the remaining 10 patients for carbamazepine (CBZ). Each drug
      was administered for 4 consecutive weeks. EEGs were recorded twice during the
      study, before and 4 weeks after the medication trial. The effects of each
      treatment on RDs were assessed. RDs disappeared in 15 of the 20 cases treated
      with CZP (75%) within 4 weeks while the same was observed in only one of the 10
      cases treated with VPA (10%). CBZ failed to demonstrate any effect on RD. In the
      group treated with CZP, there were no differences in seizure incidence, seizure
      type and blood concentration of CZP between the patients whose RDs disappeared
      and those whose RDs remained.

PMID- 9187479
TI  - Electrophysiological study of myoclonic seizures in children.
AB  - To investigate the neurophysiological mechanisms underlying myoclonic seizures in
      childhood, we measured the latency between the onset of electromyogram (EMG)
      potentials and that of corresponding spikes obtained by the back-averaging
      method. The subjects were nine patients, with various epileptic syndromes,
      ranging in age from 2 months to 15 years, 11 months. The numbers of seizure
      events obtained by averaging ranged from five to 51 with a mean of 25. The
      latencies between averaged spike-and-wave complexes and deltoid EMG potentials
      ranged from 21 to 80, with a mean of 38 ms. Comparing these results with reported
      age-matched physiological conduction times, these latencies appeared to be
      slightly prolonged in all of our patients. Our results support the hypothesis
      that myoclonic seizures are produced through either a cortical or a subcortical
      generator, via a polysynaptic mechanism acting on muscles, rather than a
      monosynaptic corticospinal pathway.

PMID- 9187480
TI  - Two different pathological conditions of photoparoxysmal responses in hereditary
      dentatorubral-pallidoluysian atrophy.
AB  - In order to reveal the pathophysiology of photoparoxysmal responses (PPRs) in
      photosensitive patients with hereditary dentatorubral-pallidoluysian atrophy
      (DRPLA) who had expansion of the CAG repeat in the DRPLA gene, we studied the
      characteristics of PPRs using optical filters with specific wavelength
      transmission. In two patients, the wavelength spectrum around 700 nm (670-720 nm)
      was apparently the only visible range essential for eliciting PPRs, and flash
      lights containing the essential wavelength elicited PPRs. In another patient,
      PPRs were elicited by flash lights above certain quantity of light and
      independent of the wavelength composition of the lights. These data suggest that
      two different pathological conditions contribute to PPRs in DRPLA patients; one
      condition depends on the essential wavelength spectrum around 700 nm, and the
      other not on the wavelength, but on the quantity of light. The condition
      contributing to PPRs in all three patients was not determined directly by the
      level of the CAG repeat expansion in the DRPLA gene.

PMID- 9187481
TI  - Developmental and aging changes in the expression of amyloid precursor protein in
      Down syndrome brains.
AB  - We studied immunohistochemically the expression of beta-amyloid precursor protein
      (APP) in the frontal lobes of 18 Down syndrome (DS) patients (20 gestation weeks
      (GW) to 50 years) and 15 controls (17 GW to 50 years) using six purified
      antibodies against the secretory forms (N-terminal, N-Amy and Amy540), the Kunitz
      type protease inhibitor (KPI) domain, residues 1-28 of beta protein (Affi28), and
      the carboxyl-terminal fragment (Ac) of APP. In the cortex of fetuses, neonates
      and infants, immunoreactivity for N-Amy and Ac was observed in both neurons and
      glial cells, and that for Affi28 in glial cells in the subpial layer in both DS
      patients and controls suggesting the functioning role of APP was a growth factor.
      This immunoreactivity disappeared in childhood and reappeared in adulthood in
      only DS patients. The earlier reappearance of those in DS patients from a young
      adult age than in normal controls may result from a gene dosage effect, since APP
      is encoded on chromosome 21. The N-Amy, Amy540, Affi28 and Ac immunoreactivity in
      glial cells in the developing white matter in the both DS patients and controls
      may be associated with myelination glia. Immunoreactivity for KPI was noted on
      the tunica media of the arteries from the neonatal period to adulthood in only DS
      patients. In senile plaques in DS patients, N-terminal and Affi28
      immunoreactivity became detectable at the age of 32 years. N-terminal
      immunoreactivity in the senile plaques was noted along the periphery of the
      senile plaques, while that for Affi28 was around the amyloid core. Thus, each
      fragment of APP exhibited a different localization and time course of
      immunohistochemical expression. The results indicated that APP plays a role in
      neuronal development and that its earlier reappearance in adult DS patients is
      associated with the regeneration process related to aging.

PMID- 9187482
TI  - Peroxisomal bifunctional enzyme deficiency: serial neurophysiological
      examinations of a case.
AB  - We report on a case of 21-month-old girl with peroxisomal bifunctional enzyme
      deficiency, which was diagnosed by means of complementation analysis. Serial
      neurophysiological examinations were also carried out. The motor and sensory
      nerve conduction velocities of the median nerve showed lower borderline values at
      3 months of age and were within range at 11 months of age. Later, those
      velocities gradually decreased. The electrically elicited blink reflex at 3
      months of age showed the prolongation of latencies of R1, R2 and R2' and the
      interpeak latencies of R1-R2 and R1-R2'. Furthermore, R1, R2 and R2' showed
      prolonged latencies at 11 months of age and were absent at 15 months of age. The
      auditory brainstem response (ABR) showed, bilaterally, normal latency of wave I,
      prolonged interpeak latencies of waves I-V. At 11 months of age, waves III and IV
      V of ABR were detected, but their amplitude was very low. At the age of 15 months
      ABR was absent. These results and the following report are valuable for
      understanding the pathogenesis of neurological symptoms.

PMID- 9187483
TI  - Pure red cell aplasia during carbamazepine monotherapy.
AB  - A 7-year-old girl developed pure red cell aplasia during carbamazepine (CBZ)
      monotherapy for epilepsy. She developed generalized clonic convulsions at the age
      of 7 years and 8 months. Treatment with CBZ was begun. Two months later she was
      admitted to our hospital because of severe anemia. Bone marrow examination
      revealed the almost complete absence of erythroblasts, with normal myelopoiesis
      and megakaryocytopoiesis, indicating pure red cell aplasia. Following the
      discontinuation of CBZ, she developed brisk reticulocytosis within 1 week and her
      hemoglobin level rose to a normal one within 1 month. Although the hematological
      toxicity of CBZ is well documented, isolated cessation of red cell production is
      uncommon. A patient who is undergoing treatment with CBZ should be carefully
      monitored, especially for serious adverse reactions including pure red cell
      aplasia.

PMID- 9187484
TI  - Isolated 3-methylcrotonyl-CoA carboxylase deficiency in a 15-year-old girl.
AB  - A 15-year-old girl with a former clinical diagnosis of cerebral palsy was found
      to have isolated deficiency of 3-methylcrotonyl-CoA carboxylase (MCC) on gas
      chromatography-mass spectrometry (GC/MS) analysis and enzyme determination. Her
      symptoms included marked growth retardation from birth, profound mental
      retardation, tonic seizures, rigospastic quadriplegia with opisthotonic dystonia,
      gastroesophageal reflux with poor esophageal peristalsis, and recurrent episodes
      of aspiration pneumonia. Brain MRI revealed marked brain atrophy, involving both
      the gray and white matter. Although she did not exhibit acute metabolic
      decompensation or acute encephalopathy, her neurological symptoms continuously
      worsened. This patient is the oldest among reported cases of MCC deficiency who
      had symptoms at birth, and this case may have the severest sequelae of the
      longest known natural course of this inborn error of metabolism.

PMID- 9187485
TI  - Effects of inorganic mercury and methylmercury on the ionic currents of cultured
      rat hippocampal neurons.
AB  - 1. The effects of inorganic Hg2+ and methylmercuric chloride in the ionic
      currents of cultured hippocampal neurons were studied and compared. We examined
      the effects of acute exposure to the two forms of mercury on the properties of
      voltage-activated Ca2+ and Na+ currents and N-methyl-D-aspartate (NMDA)-induced
      currents. 2. High-voltage activated Ca2+ currents (L type) were inhibited by both
      compounds at low micromolar concentrations in an irreversible manner. Mercuric
      chloride was five times as potent as methylmercury in blocking L-channels. 3.
      Both compounds caused a transient increase in the low-voltage activated (T-type)
      currents at low concentrations (1 microM) but blocked at higher concentrations
      and with longer periods of time. 4. Inorganic mercury blockade was partially use
      dependent, but that by methylmercury was not. There was no effect of exposure of
      either form of mercury on the I-V characteristics of Ca2+ currents. 5. Na(+)- and
      NMDA-induced currents were essentially unaffected by either mercury compound,
      showing only a delayed nonspecific effect at a time of overall damage of the
      membrane. 6. We conclude that both mercury compounds show a relatively selective
      blockade of Ca2+ currents, but inorganic mercury is more potent than
      methylmercury.

PMID- 9187486
TI  - Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2.
AB  - 1. Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic
      substrate of Parkinson's disease (PD). It is assumed that the lethal trigger is
      the accumulation of oxidative reactive species generated during metabolism of the
      natural neurotransmitter dopamine. 2. We have recently shown that dopamine is
      capable of inducing programmed cell death (PCD) or apoptosis in cultured
      postmitotic chick sympathetic neurons and rat PC12 pheochromocytoma cells. 3. The
      bcl-2 gene encodes a protein which blocks physiological PCD in many mammalian
      cells. In an attempt to elucidate further the mechanism of dopamine toxicity, we
      examined the potential protective effect of bcl-2 in PC12 cells which were
      transfected with the protooncogene. 4. In our experiments, Bcl-2 producing cells
      showed a marked resistance to dopamine toxicity. The percentage of nuclear
      condensation and DNA fragmentation visualized by the end-labeling method
      following dopamine treatment was significantly lower in bcl-2 expressing cells.
      Bcl-2 did not protect PC12 cells against toxicity induced by exposure to dopamine
      melanin. Extracts of PC12 cells containing Bcl-2 inhibited dopamine autooxidation
      and formation of dopamine-melanin. Furthermore, the presence of Bcl-2 protected
      cells from thiol imbalance and prevented thiol loss following exposure to
      dopamine. 5. The protective effects of Bcl-2 against dopamine toxicity may be
      explained, in part, by its action as an antioxidant and by its interference in
      the production of toxic agents. The possible protection by Bcl-2 against neuronal
      degeneration caused by dopamine may play a role in the pathogenesis of PD and may
      provide a new direction for the development of neuroprotective therapies.

PMID- 9187487
TI  - Lead reduces depolarization-induced calcium entry in cultured DRG neurons without
      crossing the cell membrane: fura-2 measurements.
AB  - 1. Cultured dorsal root ganglion of rat pups were depolarized by exposure to 50
      mM K+ and the rise of [Ca2+]i was measured using fura-2 as an indicator. 2. Lead
      in the extracellular solution reduced the rise of [Ca2+]i in a concentration
      dependent manner, with a threshold concentration of 0.25 microM. More than 80% of
      the calcium entry was prevented by approximately 5 microM lead. The IC50 and the
      Hill coefficient were 3.1 microM and 1, respectively. 3. This effect was
      considered to be due to a reduction of VACCCs, since applications of NMDA did not
      result in any rise of [Ca2+]i. 4. Since Pb2+ itself changes the fura-2 signal in
      a typical and characteristic manner, fura-2 is also an indicator for Pb2+. No
      changes in fura-2 signals were detected when lead (5 microM) was applied for
      several minutes in the absence of calcium, indicating that Pb2+ did not enter the
      cells. 5. Thus it is concluded that lead prevents calcium entry by reducing
      VACCCs but does not cross the cell membrane itself.

PMID- 9187488
TI  - Normal and atypical butyrylcholinesterases in placental development, function,
      and malfunction.
AB  - 1. In utero exposure to poisons and drugs (e.g., anticholinesterases, cocaine) is
      frequently associated with spontaneous absorption and placental malfunction. The
      major protein interacting with these compounds is butyrylcholinesterase (BuChE),
      which attenuates the effects of such xenobiotics by their hydrolysis or
      sequestration. Therefore, we studied BuChE expression during placental
      development. 2. RT-PCR revealed both BuChEmRNA and acetylcholinesterase (AChE)
      mRNA throughout gestation. However, cytochemical staining detected primarily
      BuChE activity in first-trimester placenta but AChE activity in term placenta. 3.
      As the atypical variant of BuChE has a narrower specificity for substrates and
      inhibitors than the normal enzyme, we investigated its interactions with alpha
      solanine and cocaine, and sought a correlation between the occurrence of this
      variant and placental malfunction. 4. Atypical BuChE of serum or recombinant
      origin presented > 10-fold weaker affinities than normal BuChE for cocaine and
      alpha-solanine. However, BuChE in the serum of the heterozygote and a homozygous
      normal were similar in their drug affinities. Therefore, heterozygous serum or
      placenta can protect the fetus from drug or poison exposure, unlike homozygous
      atypical serum or placenta. 5. Genotype analyses revealed that heterozygous
      carriers of atypical BuChE were threefold less frequent among 49 patients with
      placental malfunction than among 76 controls of the entire Israeli population.
      These observations exclude heterozygote carriers of atypical BuChE from being at
      high risk for placental malfunction under exposure to anticholinesterases.

PMID- 9187489
TI  - Rat hypothalamus neuron-like cells in primary culture accumulate and translate
      mRNA coding for the amphibian P-domain peptide xP1.
AB  - 1. Neurons seem to possess the intrinsic capability to incorporate and translate
      exogenous RNA. For further evaluation of this phenomenon, we wanted to study the
      uptake and processing capacity of rat hypothalamic neurons for species-unspecific
      heterologous cRNA under in vitro conditions. 2. cRNA coding for the amphibian p
      domain peptide xP1 was prepared by in vitro transcription and added to the
      culture medium of rat hypothalamic cells, derived from E18 fetuses. 3. After 2
      hr, a fraction of the hypothalamic neuron-like cells had accumulated the
      radiolabeled transcripts, as could be demonstrated by autoradiographic
      assessment. Specific immunostaining for xP1 could be demonstrated 18 hr after
      incubation with the cRNA. 4. Our findings indicate that hypothalamic neuron-like
      cells are capable of accumulating and translating nonmammalian transcripts. Since
      it was only a portion of hypothalamic cells that showed this effect, specific
      recognition sites for RNA may be presented by certain neurons, further supporting
      the assumption that binding, uptake, and translation of cRNA transcripts
      represent a general neural property which is malleable to functional status.

PMID- 9187492
TI  - Stable expression of anti-HPV 16 E7-ribozyme in CV-1 cell lines.
AB  - The HPV16 (human papilloma virus type 16) E7 gene product, an oncoprotein, has
      been considered to be involved in the pathogenesis of anogenital cancer,
      particularly of cervical cancer. In order to evaluate the effect of suppression
      of the expression of the E7 gene in CV-1 cells by ribozyme, Rz523 with a
      transacting ribozyme targeted to the E7 RNA and two processing ribozyme genes at
      the 5' and 3' flank was cloned into the eukaryotic expression plasmid pREP9 under
      the control of RSV-LTR promoter. The resultant plasmid pRSV-Rz523 was transfected
      into CV-1 cells by calcium phosphate coprecipitation. The expression of the
      ribozyme in G418-resistant cells was detected by dot-blot hybridization.
      Ribozymes stably expressed in the CV-1 cells were at a level of 9.0 pmol per
      10(6) cells, in which the active ribozyme molecules were more than 50 fmol per
      10(6) cells. The result of RNase protection assay showed that the steady-state
      level of the E7 RNA fragment in CV-1 cell lines was significantly reduced by
      about 90% in ribozyme-expressing cells. In contrast, the antisense control
      plasmid pRSV-AE7 only exhibited about 20%. This result implicated the possibility
      of reversing the malignant phenotype of cervical cancer by means of suppressing
      the expression of the E7 gene with ribozyme.

PMID- 9187491
TI  - T7-promoter-based Escherichia coli expression system induced with bacteriophage
      M13HEP.
AB  - The bacteriophage M13HEP was constructed by cloning the T7 RNA polymerase gene
      into phage M13mp18 RF DNA to express T7 RNA polymerase under the control of the
      lac promoter. Through M13HEP phage infection, T7 RNA polymerase could be
      introduced into an expression strain and heterologous genes under the control of
      the T7 promoter can be induced to express. Using this phage M13HEP induction
      system, many heterologous genes, especially some genes whose products are toxic
      to the host strain, were successfully expressed. By transferring F' pilli from E.
      coli XL1-blue to E. coli HMS174, a new E. coli strain HMS174F' was obtained to
      make the construction, expression, and single-stranded DNA rescue of the T7
      expression plasmid be conveniently performed in the same strain.

PMID- 9187493
TI  - Identification of somatic hybrids between rice cultivar and wild Oryza species by
      RAPD.
AB  - The somatic hybrids between rice cultivar and wild Oryza species were obtained by
      the PEG and electrical fusion method. The somatic hybrids were identified with
      PAPD. It was verified that the genome of somatic hybrids contained some genomes
      from both parents, but they contributed unequally. In some somatic hybrids, the
      portion from one parent was more than the other. The relationship between somatic
      hybrids and their parents was analyzed based on RAPD data.

PMID- 9187494
TI  - Cloning of the human erythropoietin exons and their expression in COS-7 cells.
AB  - Human erythropoietin exons (hEPO-E) were isolated from a Chinese fetal liver DNA
      library by using the PCR method with gene recombination. One nucleotide mutation
      was found in exon 3 leading to the Leu in position 62 being changed to Ser. The
      hEPO-E coding for the full-length mature protein was inserted into different
      clone sites of PSV-2-dhfr to create different transferring plasmids (pSV2
      dhfr/F1, pSV2/F2, pSV2-dhfr/F3, pSV2-dhfr/F4, pSV2-dhfr/G1, and pSV2-dhfr/G3)
      which were transfected into COS-7 cells. Results obtained from the comparative
      experiments indicate that biological activity of hEPO was found in all culture
      supernatants and its expression level was higher than that of its genome.

PMID- 9187495
TI  - Ultra low temperature cryopreservation of somatic embryogenic cell line of
      foxtail millet [Setaria italica (L.) Beauv].
AB  - Ultra low temperature cryopreservation is one of the methods for preservation of
      biological material. Until now, a major problem of protoplast culture of
      Gramineae is the instability of state of the somatic embryogenic cell line. In
      our experiments, elements affecting the ultra low temperature cryopreservation of
      somatic embryogenic cell line were studied: components of cryopreserve solution,
      somatic embryogenic cell line of different subculture time, growth recovery of
      cryopreserved cell line, and their protoplast cultures. Results demonstrated that
      the ultra low temperature cryopreservation did not change the properties of
      protoplast culture, and by using the cryopreserve method, plating efficiency of
      protoplast culture of cryopreserved cell line was maintained or enhanced.

PMID- 9187496
TI  - Multichannel flow electrophoresis and its applications in purification of
      proteins, enzymes, and antibodies.
AB  - Multichannel flow electrophoresis (MFE) is a novel preparative electrophoresis
      technique designed for continuous separation of proteins based on their different
      isoelectric points. A computer controlled MFE apparatus is developed and the
      effects of operation parameters such as electric field strength, buffering pH,
      and sample introducing flow rate on MFE separation efficiency are investigated.
      The application of MFE is first exemplified by continuous separation of BSA and
      HBB mixture. Then continuous purification of urokinase from urine extracts is
      conducted, in which 10 x 10(4) IU urokinase product whose specific activity is
      higher than 40,000 IU/mg is obtained per hour. Finally, MFE is applied in the
      continuous purification of anti-urokinase mouse IgG from mouse serum and yields
      2.1 mg mouse IgG per hour with high purity demonstrated by SDS-PAGE. The
      preliminary results presented have confirmed the workability of MFE and pointed
      out its high application potential in biochemical process.

PMID- 9187497
TI  - PCR analysis of half-seeds of cereal crops and its application in marker-assisted
      selection and breeding.
AB  - A simple and rapid PCR method was adapted to DNA analysis of cereal seeds. Half
      seeds of rice, wheat, and maize were treated with an extraction buffer and the
      resulting supernatants were used in PCR and RAPD reactions. PCR products
      amplified from the half-seed DNA extracts were identical with that from leaf
      tissue DNA extracts when the same specific primers were used in PCR reactions.
      The remaining half-seeds with embryos could still germinate normally. The half
      seed PCR analysis was applied to the identification of resistant genotypes of
      rice bacterial blight, and it was proved effective in plant breeding and genetic
      studies.

PMID- 9187490
TI  - Cellular basis of pontine ponto-geniculo-occipital wave generation and
      modulation.
AB  - 1. Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement
      (REM) sleep from the pontine reticular formation. 2. PGO wave-like field
      potentials can also be recorded in many other parts of the brain in addition to
      the pontine reticular formation, but their distribution is different in different
      species. Species differences are due to variation in species-specific
      postsynaptic target sites of the pontine PGO generator. 3. The triggering neurons
      of the pontine PGO wave generator are located within the caudolateral
      peribrachial and the locus subceruleus areas. 4. The transferring neurons of the
      pontine PGO generator are located within the cholinergic neurons of the
      laterodorsal tegmentum and the pedunculopontine tegmentum. 5. The triggering and
      transferring neurons of the pontine PGO wave generator are modulated by
      aminergic, cholinergic, nitroxergic, GABA-ergic, and glycinergic cells of the
      brainstem. The PGO system is also modulated by suprachiasmatic, amygdaloid,
      vestibular, and brainstem auditory cell groups.

PMID- 9187498
TI  - Purification of phosphoglycerate kinase and glyceraldehyde phosphate
      dehydrogenase by DEAE-sepharose fast flow chromatography.
AB  - The purification of phosphoglycerate kinase (PGK) and glyceraldehyde phosphate
      dehydrogenase (GAPDH) from soy bean was studied by a DEAE-sepharose fast flow
      chromatography. When scaling up, the diameters of columns increase but the
      heights of columns were maintained in the range of 10 to 20 cm to avoid the
      problem of the high pressure drop. The recovery of GAPDH and PGK was 57% and 41%,
      respectively. The purification factor of GPADH and PGK was 144 and 44,
      respectively. The economical evaluation indicated that the cost of the process
      was 2.09$/ku GAPDH, which has some commercial values.

PMID- 9187499
TI  - Construction of a brewing yeast having glucoamylase activity and its fermentation
      characteristics.
AB  - The brewing yeast having glucoamylase activity was constructed by integrating
      glucoamylase cDNA from Asapergillus niger into the genome of brewing yeast B48.
      The integration was achieved by cotransformation of YEP type plasmid pKG1
      carrying glucoamylase expression-secretion element and was verified by Southern
      blot analysis. The engineered yeast was stable, and the fermentation test
      demonstrated that the lower residual dextrin level was obtained compared with
      control strain B48. Thus the fermentation rate was raised to 80.5%. No alteration
      of growth and brewing properties was observed. Beer quality was judged to be
      good.

PMID- 9187501
TI  - Actin polymerisation in neutrophils of rheumatoid arthritis patients in relation
      to treatment with non-steroidal anti-inflammatory drugs.
AB  - There is evidence that neutrophil functions such as chemotaxis and oxygen radical
      formation are disturbed in rheumatoid arthritis (RA). Medication might also
      influence these functions. Cyclic formation and depolymerisation of actin
      microfilaments is crucial in cell motility, but this phenomenon has not been
      studied in RA. The aim of this study was to investigate basal and dynamic (formyl
      methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in
      ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs
      (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of
      ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was
      significantly lower than in RA patients without NSAIDS and controls: 35.5 (25.0
      49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon
      stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS
      was higher than for RA patients without NSAIDS and controls. These results
      suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be
      related to changes in the actin polymerisation-depolymerisation cycle.

PMID- 9187500
TI  - Solid phase competitive luminescence immunoassay for immunoglobulin A in faeces:
      development and clinical validation.
AB  - We describe a new simple solid-phase competitive luminescence immunoassay (LIA)
      for the determination of immunoglobulin A (IgA) in faeces. The assay utilizes an
      anti-alpha-chain IgA antibody which is coated to polystyrene beads and acridinium
      ester-labelled human IgA as tracer and, therefore, measures both monomeric and
      polymeric IgA. Dilution recovery of an internal standard was 96, 100 and 103%.
      Interassay and intra-assay coefficients of variation (C.V.) ranged from 4.5 to
      12.9%. The upper limit of normal of faecal IgA in 122 healthy controls was found
      to be 300 mg/l IgA (mean 73 mg/l, specificity of 99.2%). Patients with inactive
      Crohn's disease (Crohn's disease activity index (CDAI < 150, n = 14) had faecal
      IgA values up to 3317 mg/l (mean 1073 mg/l; P < 0.0001). In the active group
      (CDAI > 150, n = 26) faecal IgA values ranged from 49 to 4094 mg/l (mean 1253
      mg/l; P < 0.0001). Patients with ulcerative colitis were divided into a group
      with active disease (n = 18) and a remission group (n = 16) with values up to
      1843 mg/l faecal IgA (man 486 mg/l; P < 0.0032) and up to 602 mg/l faecal IgA
      (mean 176 mg/l; P < 0.4833), respectively. We also studied patients with non
      inflammatory diseases of the gut with this assay. This LIA has proved to be a
      reliable method for the determination of elevated faecal IgA concentrations and
      for the detection of pathological findings in the gastrointestinal tract,
      especially in Crohn's disease.

PMID- 9187502
TI  - Nonsense mutation in exon 2 of the butyrylcholinesterase gene: a case of familial
      cholinesterasemia.
AB  - A point mutation that causes a silent phenotype for human serum
      butyrylcholinesterase (BChE) was proved by DNA analyses of a 64-year-old Japanese
      female who visited the hospital because of a common cold. The propositus and her
      two siblings showed extremely low BChE activity, but other family members (six
      individuals) manifested from intermediate to normal values of BChE activity. An
      immunological method revealed that the propositus and her two siblings showed
      absence of the BChE protein in serum. DNA sequence analysis of the propositus
      identified a point mutation at codon 400 (TGC-->TGA), resulting in the production
      of a stop codon. This alteration exists upstream of the Cys571 of the subunit,
      which forms a disulfide bridge with the Cys571 of another partner subunit.

PMID- 9187503
TI  - Reference ranges of normal blood catalase activity and levels in familial
      hypocatalasemia in Hungary.
AB  - In 1756 healthy individuals the mean and S.D. values of blood catalase activity
      were 111.3 +/- 16.5 MU/l with lower blood catalase for females (107.7 +/- 14.4
      MU/l, n = 880) than for males (117.9 +/- 16.8 MU/l, n = 876) while the ratios of
      blood catalase activity to blood hemoglobin concentration were not different
      (0.841 +/- 0.107 MU/g versus 0.849 +/- 0.119 MU/g). The decrease of blood
      catalase with age was greater in males (b = -0.084 MU/l year) than in females (b
      = -0.016 MU/l year). The screening of 3300 healthy citizens for hypocatalasemia
      yielded six families (0.18%), and three families were identified out of 1630
      clinic patients. These nine families revealed 37 hypocatalasemic patients with
      57.5 +/- 11.7 MU/l mean and S.D. of blood catalase activity. Similarly to the
      Japanese and the Hungarian actalasemic patients, the electrophoretic mobilities
      of catalase in erythrocytes of hypocatalasemic patients were indistinguishable
      from that of healthy controls.

PMID- 9187504
TI  - The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors.
AB  - Fibrinolytic enzyme inhibitors hamper the determination of the specific
      fibrinolytic serine protease activity. Reportedly, chemical anti-inhibitors
      eliminate the influence of fibrinolytic inhibitors, but it remains unclear to
      what extent they change the specific activity of fibrinolytic serine proteases.
      We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate,
      sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and
      fibrinolytic enzyme inhibitors using the physiological substrate fibrin as
      plasmin substrate. Low concentrations of chloramine T (0.01 mmol/l) prevent the
      inhibition of plasminogen activators. Higher concentrations (1 mmol/l) reduce the
      inhibition of plasmin, but simultaneously quench the plasminogen activator
      activity. Flufenamate eliminates most fibrinolytic enzyme inhibitors, but
      increases the activity of plasmin (apparent recovery 140%) and plasminogen
      activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major
      fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent
      recovery > 200%) and plasminogen activator, urokinase type (apparent recovery
      130%). Methylamine affects only plasmin inhibition. We conclude that chemical
      anti-inhibitors may invalidate the analytical specificity of methods for the
      determination of fibrinolytic serine protease activity.

PMID- 9187505
TI  - Augmented release of brain natriuretic peptide during reperfusion of the human
      heart after cardioplegic cardiac arrest.
AB  - The aim of the study was to investigate the release of natriuretic peptides
      during myocardial ischaemia and reperfusion associated with cardioplegic cardiac
      arrest. Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP)
      concentrations were measured in paired arterial, central venous and coronary
      sinus blood samples in 19 patients undergoing elective coronary artery bypass
      grafting before aortic crossclamping and 1, 5, 10 and 20 min after aortic
      declamping. Peak myocardial BNP release after aortic declamping was significantly
      higher than baseline values before aortic crossclamping. Both peak and cumulative
      BNP release during reperfusion correlated significantly with the severity of
      ischaemia, as assessed by myocardial lactate production. In 3 patients with
      perioperative myocardial ischaemia, cumulative and peak myocardial BNP release
      after aortic unclamping was markedly higher than in the remaining 16 uneventful
      patients. Myocardial ANP release during reperfusion was not significantly
      different from baseline values before aortic crossclamping. In conclusion, our
      data demonstrate a significantly enhanced myocardial BNP release early during
      reperfusion of the human heart after global ischaemia associated with
      cardioplegic cardiac arrest.

PMID- 9187506
TI  - Effect of gamma-interferon on binding of gliadin and other food peptides to the
      human intestinal cell line HT-29.
AB  - gamma-Interferon is one of the main cytokines released during activation of
      intestinal lymphocytes in coeliac patients. The question has never been addressed
      whether gamma-interferon influences binding of gliadin and other food peptides to
      human enterocytes. Therefore, the human intestinal epithelial cell line HT-29 was
      cultured with gliadin, casein, beta-lactoglobulin and ovalbumin, with or without
      gamma-interferon, and peptide binding to cells was determined by flow cytometry
      and fluorescence microscopy. gamma-Interferon stimulated gliadin binding by a
      factor of 4. Binding was saturable with half maximal binding at 0.15 mg/ml. For
      maximal binding, an incubation of at least 24 h was necessary. gamma-Interferon
      increased binding of beta-lactoglobulin and casein, too, but inhibited that of
      ovalbumin. Binding of gliadin was inhibited by the other peptides. Under the
      conditions of ongoing mucosal inflammatory reactions and release of gamma
      interferon, enhanced binding may trigger intestinal lymphocytes, increase
      secretion of cytokines and thus induce a vicious circle.

PMID- 9187507
TI  - Plasma vitronectin concentrations in patients with chronic hepatitis C treated
      with interferon alpha.
AB  - Plasma vitronectin concentration was measured in 60 patients with chronic
      hepatitis C before and after interferon alpha treatment. The plasma pretreatment
      levels of vitronectin in the interferon non-responders was significantly lower
      than those in the interferon sustained and transient responders, but the levels
      were not different in the latter two groups. After interferon therapy, the plasma
      levels of vitronectin were significantly increased in all three groups, and they
      were correlated with the albumin levels. Absolute changes of plasma vitronectin
      before and after interferon treatment were significantly related to initial
      levels, but they were not related to those of albumin or alanine aminotransferase
      levels. The values of sensitivity and specificity for plasma vitronectin in the
      sustained responder and non-responder were 45% and 95% for each. These results
      suggest that chronic hepatitis C patients with low levels of plasma vitronectin
      may have a weak response in interferon therapy.

PMID- 9187508
TI  - Effects of lead and manganese on the release of lysosomal enzymes in vitro and in
      vivo.
AB  - In this study we evaluated the effects of two heavy metals, lead and manganese,
      on the release of some glycohydrolases of lysosomal origin. N-acetyl-beta-D
      glucosaminidase and its major isoenzymes, beta-D-glucuronidase and alpha-D
      galactosidase. We have studied release of these enzymes in vitro from peripheral
      mitogen-activated lymphocytes from healthy subjects after addition of Pb or Mn to
      the medium and their plasma levels in individuals exposed at work to Pb (31
      subjects) or to manganese (36 subjects), versus matched controls. We also
      determined the plasma levels in a general population (417 subjects). The
      enzymatic activities were assayed fluorimetrically with 4-methylumbelliferyl
      glycosides as substrates. Particular attention was given to some technical
      aspects: enzymatic activity was preserved by addition of ethylene glycol and
      stable liquid material was employed for calibration purposes. N-acetyl-beta-D
      glucosaminidase isoenzymes were separated by a routine chromatofocusing procedure
      on PBE 94. The addition of both metals to lymphocytes inhibits lysosomal enzyme
      release. These data were supported by the plasma levels for the exposed subjects,
      in which enzyme levels were significantly decreased after either type of
      exposure. In the general population of subjects not professionally exposed, the
      effect of lead appears to be masked by concomitant effects of alcohol
      consumption. Undoubtedly, some heavy metals can alter distribution of
      glycohydrolases of lysosomal origin between the intra- and extracellular
      environment, probably interfering with membrane mechanisms. Lysosomal enzymes
      seem to behave as sensitive biomarkers for early subclinical changes that might
      later lead to clinical disease.

PMID- 9187509
TI  - The Snider Address. A four-decade adventure in experimental liver injury.

PMID- 9187510
TI  - Covalent binding of xenobiotics to specific proteins in the liver.
AB  - Chemicals that cause toxicity though a direct mechanism, such as acetaminophen,
      covalently bind to a select group of proteins prior to the development of
      toxicity, and these proteins may be important in the initiation of the events
      that lead to the hepatotoxicity. Disruption of the cell is measured by release of
      intracellular proteins such as alanine aminotransferase and occurs late in the
      time course following a hepatotoxic dose of a direct toxin. Prior to this
      disruption, there appears to be a large number of proteins covalently modified by
      a reactive metabolite. There are at least two possible mechanisms that may cause
      the toxicity. First, some critical protein is a target of the reactive
      metabolite. Disruption of the enzymatic function (or a critical pathway for a
      regulatory protein) may lead directly to cell death. With the direct hepatotoxin
      acetaminophen, there is a decrease in the activity of several of the early target
      proteins, but how this disruption of critical proteins leads to the toxicity is
      still unclear. The early targets appear to be proteins with accessible
      nucleophilic sulfhydryl groups, and usually the target has a high concentration
      of the protein within the cell. It is possible that the binding to some of these
      proteins represents a detoxification protecting more critical targets within the
      cell. A second mechanism for the direct toxicity is that more and more proteins
      become targets in the time course following administration of a direct toxin, and
      eventually the cells machinery is overwhelmed. The cell can then no longer
      function, or there is a disruption the redox balance within the cell due to the
      decreased function of numerous proteins. In contrast to the direct-acting toxins,
      the chemical-protein conjugates that initiate toxicity through an activation of
      the immune system appear to have a limited number of target proteins and are
      localized within one subcellular fraction. Halothane produces adducts almost
      exclusively in the microsomal fraction, and these adducts appear to be limited to
      selective proteins with high concentrations in this fraction. The substitution
      level is an important factor in the development of an immune response. Halothane
      hepatitis patients' antibodies primarily recognize proteins with a high
      substitution level. For halothane and diclofenac, the proteins are accessible to
      the immune system through exposure on the plasma membrane. Trichloroethylene
      binds primarily to a 50-kDa microsomal protein, and preliminary evidence has been
      presented which indicates that a trichloroethylene-protein conjugate is released
      into the blood following exposure, where contact with the immune system can
      occur. In order to elicit an immune response the immune system requires multiple
      exposure to the chemical-protein conjugates. With halothane hepatitis and with
      diclofenac hepatitis, as well as occupational and environmental exposure to
      trichloroethylene, there are multiple exposures leading to repeat presentation of
      the protein adducts to the immune system; this situation is not generally found
      with acetaminophen overdose patients. In summary, direct toxicants such as
      acetaminophen covalently bind to selected targets which may be critical to the
      development of hepatotoxicity, and they later form adducts with numerous proteins
      which may overwhelm the cell's capacity to maintain homeostasis, leading to loss
      of vital function and cell death (Fig.3). In contrast, indirect toxicants that
      elicit an immune-mediated toxicity such as halothane, and possibly diclofenac and
      trichloroethylene, appear to have a limited number of protein targets with a high
      substitution level, and the immune system is exposed repeatedly to the modified
      proteins.

PMID- 9187511
TI  - Selective protein arylation and acetaminophen-induced hepatotoxicity.
AB  - More than 20 years have passed since the early reports of acute hepatotoxicity
      with APAP overdose. During that period investigative research to discover the
      "mechanism" underlying the toxicity has been conducted in many species and
      strains of intact animals as well as in a variety of in vitro and culture
      systems. Such work has clarified the primary role of biotransformation and the
      protective role of GSH. Understanding the former provides explanations for the
      toxic interactions which may occur with alcohol or other xenobiotics, while
      understanding of the latter led to the development of antidotes for the treatment
      of acute poisoning. Acetaminophen (APAP)-induced hepatotoxicity: roles for
      protein arylation. Initiating events in toxicity require biotransformation of
      APAP to NAPQI followed by arylation of several important proteins with subsequent
      alteration of protein structure and function. The immediate consequence of the
      alterations is detectable in several organelles and these may represent multiple
      initiating events which are depicted as acting in concert to cause cell injury
      (large arrowheads). Arylation of cytosolic 58-ABP with subsequent translocation
      to the nucleus is depicted as a possible signaling mechanism for determining
      outcome at the cell or organ level (within dotted boundary). For simplicity
      NAPQI's potentials for oxidizing protein sulfhydryls and direct binding to DNA
      have been omitted. Significant light has also been shed on the biochemical and
      cellular events which accompany APAP-induced hepatotoxicity. However, such
      studies have not identified a unique mechanism of toxicity that is universally
      accepted. The recent identification of several protein targets which become
      arylated during toxicity--along with the findings that arylation of some of those
      target proteins results in loss of protein function--demonstrates that covalent
      binding does, indeed, have biological consequences and is not merely an indicator
      of the fleeting presence of reactive electrophiles. These observations further
      suggest that multiple independent insults to the cell may be involved in
      toxicity. it is now apparent that the concept of a multistage process that
      involves both initiation and progression events is appropriate for APAP toxicity,
      and it is unlikely that a unique initiating event will ever be identified. In
      light of recent findings it is more likely that a number of such cellular events
      occur very early after toxic overdosage, and that they collectively set in motion
      and perpetuate the biochemical, cellular, and molecular processes which will
      determine outcome. The importance of 58-ABP arylation with early, apparently
      selective, translocation to the nucleus remains to be elucidated. To date there
      is nothing to suggest that this represents an initiating event in toxicity.
      rather it is plausible that the translocation may play a role in signaling
      electrophile presence and in calling for cellular defense against electrophile
      insult. This is reflected in the hypothetical model presented in Fig. 3. Critical
      experimental testing of this model will advance our understanding of the cellular
      and molecular responses to toxic electrophile insult.

PMID- 9187512
TI  - Role of metallothionein in cadmium-induced hepatotoxicity and nephrotoxicity.
AB  - MT, a cysteine-rich, metal-binding protein, exists in most tissues and is easily
      induced by many stimuli. There are four major MT isoforms in mammalian tissues,
      with MT-I and -II present in all tissues, MT-III only in brain, and MT-IV located
      in epithelium. Many factors regulate MT synthesis, such as age, species,
      hormones, inflammation, and various chemical treatments. Not only is MT synthesis
      important, but degradation of MT is also an important mechanism of MT regulation.
      The importance of MT in Cd toxicology has been extensively investigated. MT does
      not have a major effect on absorption and tissue distribution of Cd, but it does
      play a major role in binding Cd in the cell, thus decreasing its elimination from
      the body, especially into the bile. MT is at least partially responsible for the
      retention of Cd in tissues and the long biological half-life of the metal. MT
      plays an important role in Cd tolerance and Cd-induced hepatotoxicity. MT binds
      Cd in the hepatic cytosol and renders it "inert." Therefore, MT is beneficial to
      the liver. However, the Cd-MT complex is nephrotoxic and is proposed to be
      responsible for chronic Cd poisoning. MT appears to play less of a protective
      role in Cd-MT-induced acute nephrotoxicity, and Zn-induced protection against
      CdMT acute renal injury is not mediated by MT. The role of MT in chronic Cd
      nephrotoxicity needs to be further clarified.

PMID- 9187513
TI  - Characterization of the humoral immune response and hepatotoxicity after multiple
      halothane exposures in guinea pigs.

PMID- 9187514
TI  - The hepatic interaction of aliphatic alcohols with halogenated hydrocarbons.
AB  - As has been noted, advancement in understanding of chemical interactions requires
      an integrated approach. Given the large number of binary mixtures of aliphatic
      alcohols and halogenated hydrocarbons that can be formulated, and because
      limitations of time and resources make it impossible to test them all, careful
      thought should be given to selection of pairs for laboratory experimentation. For
      any given pair of chemicals, the type of interaction (addition, synergism,
      antagonism, potentiation) should be determined and described by appropriate
      experimental designs and statistical methodology. This has been done for various
      alcohol-halocarbon mixtures. Work to expand our understanding of the mechanism(s)
      underlying the interaction of aliphatic alcohols and halogenated hydrocarbons
      would be particularly useful, as an improved mechanistic understanding would
      improve our ability to extrapolate across dose levels (from high laboratory
      exposure concentrations to typical human environmental exposure concentrations)
      and across species (from laboratory animals to humans).

PMID- 9187515
TI  - Patterns of liver injury induced by mixtures of halogenated hydrocarbons: a
      predictable event?

PMID- 9187516
TI  - Neutrophil- and glutathione-mediated hepatotoxicity of alpha
      naphthylisothiocyanate.
AB  - In summary, both glutathione and blood neutrophils contribute to ANIT
      hepatotoxicity. Glutathione contributes by virtue of its ability to form a
      reversible S-conjugate with ANIT that is critical in shuttling ANIT into bile.
      Where it is released in large and probably toxic concentrations. The possibility
      remains that this conjugate may be bioactivated by secondary mechanisms, but no
      evidence for a toxic glutathionyl conjugate of ANIT currently exists. Neutrophils
      and platelets both appear to play important roles in ANIT hepatotoxicity. The
      role of platelets is currently unknown, but studies in vitro raise the
      possibility that neutrophils may be activated during ANIT exposure to release
      cytotoxic proteases that cause injury to target cells. Although ANIT activates
      neutrophils in vitro, the mechanisms by which neutrophils are recruited into the
      periportal region and activated in vivo remain unknown.

PMID- 9187517
TI  - Monohydroxy bile acid induced cholestasis: role of biotransformation.

PMID- 9187518
TI  - Cholestatic properties and hepatic transport of steroid glucuronides.
AB  - In summary, the data suggest that E217G is transported by both MOAT and P
      glycoprotein into bile, but that P-glycoprotein serves as the target site for
      cholestasis. We postulate that this target site may be accessed from either the
      intracellular compartment or the canaliculus, and that MOAT serves as the major
      delivery route for E217G to the canaliculus. At low, physiologic concentrations
      of E217G, MOAT-mediated excretion into bile is a detoxification mechanism,
      serving to prevent intracellular accumulation of a toxic metabolite. However,
      following administration of high, cholestatic doses, MOAT-mediated excretion into
      bile results in very high concentrations in bile, on the other of 2-3 mM (see
      Fig. 4). It is likely that the hydrophobic nature of E217G allows it to partition
      from bile into the canalicular membrane, from which it can access P-glycoprotein
      and thus induce cholestasis. Much work is still needed to validate this model of
      E217G cholestasis. Definitive evidence of P-glycoprotein-mediated transport of
      E217G must be obtained in cell lines transfected with P-glycoprotein where MRP is
      absent. More importantly, the mechanism by which interaction of E217G with P
      glycoprotein influences bile flow is unknown. Higgins and colleagues have
      provided evidence that P-glycoprotein regulates a Cl- channel in a manner
      analogous to that of CFTR, the cystic fibrosis transmembrane conductance
      regulator. While Cl- channels have been shown to be important in the regulation
      of the volume of the hepatocyte in the presence of altered osmotic conditions, a
      role for this channel in bile flow has not been demonstrated. Nevertheless, these
      studies implicate a role of P-glycoprotein in the regulation of bile secretion by
      the liver.

PMID- 9187519
TI  - Metabolism of Eucalyptus terpenes by herbivorous marsupials.

PMID- 9187520
TI  - Pharmacokinetics and metabolism of lonidamine in rats: evidence of enterohepatic
      recycling.

PMID- 9187521
TI  - Mitogenic actions of peroxidase proliferators: involvement of protein kinase C
      and tumor necrosis factor alpha.

PMID- 9187522
TI  - Metallothionein in physiological and physiopathological processes.
AB  - The multipurpose nature of MT that we have presented in this review has drawn
      attention from many different fields of research: biochemistry, molecular
      biology, toxicology, pharmacology, etc. In recent years, considerable advances
      have been made concerning the regulation of MT genes by metals. Little, however,
      is known at the molecular level about the mechanisms of MT induction by
      nonmetallic inducers such as growth factors. This is of particular interest since
      MT is highly expressed during liver regeneration, an event orchestrated by a
      series of growth stimulators and inhibitors. The significance of the nuclear
      distribution of MT in growing cells and what controls its translocation are
      questions that remain unanswered at the present time. The possibility that MT
      could participate in a DNA synthesis-related process through donation or
      abstraction of Zn to and from transcription factors has been inferred from in
      vitro studies. Such transfer mechanisms, however, have yet to be confirmed in
      vivo. Overexpression of MT is often accompanied by increased resistance towards a
      variety of alkylating agents and chemotherapeutic drugs. The mechanisms by which
      MT protects cells against these agents may depend on their distinct mode of toxic
      action. For some, MT cysteines can be the target of the direct attack from the
      parent compound. For others such as N-methyl-N-nitroso compounds, MT cysteines
      may serve as a sink for the reactive oxygen species now known to be derived from
      their metabolism. In either case, a primary consequence of such interactions is
      the release of the metals initially bound to MT. Therefore, the metal composition
      of MT appears to be an important factor to consider in determining the overall
      effect of MT in the resistance process.

PMID- 9187523
TI  - Pharmacology and pharmacokinetics of LEX 032, a bioengineered serpin: the first
      of a potential new class of drugs.

PMID- 9187524
TI  - Adrenergic modulation of hepatotoxicity.
AB  - Summaries of the interactions caused by altering adrenoreceptor activity in
      conjunction with the administration of selected hepatotoxicants are provided in
      Table 2 and Fig. 1. These hepatotoxicants can be divided into two groups, one
      whose toxicity is increased by adrenergic agonist drugs (group I) and the other
      whose toxicity is decreased by adrenergic antagonists (group II). Group I
      includes carbon tetrachloride, acetaminophen, and methylphenidate. Perhaps the
      most remarkable aspect these chemicals have in common is the striking
      potentiation that occurs with cotreatment with certain adrenergic agonist drugs.
      For each of these, cotreatment with the appropriate adrenergic agent can result
      in massive hepatocellular necrosis from an otherwise nontoxic dose. In terms of
      the specific adrenoreceptors involved and mechanisms of potentiation, however,
      they have little in common. Potentiation of carbon tetrachloride hepatotoxicity
      appears to be mediated by alpha(2)-adrenoceptor stimulation, acetaminophen is
      potentiated by alpha(1)-adrenoreceptor agonists, and methylphenidate responds to
      beta(2)-adrenoreceptor stimulation. Studies of the potentiation of carbon
      tetrachloride and acetaminophen agree that the timing of adrenergic stimulation
      relative to the hepatotoxicant dose is critically important to the interaction
      but markedly different for these two toxicants. Acetaminophen was potentiated
      only when the adrenergic drug was administered as a 3-h pretreatment. This is
      apparently a consequence of a mechanism of potentiation that involves adrenergic
      depression of hepatic glutathione content and a requirement that peak effects on
      glutathione of both the adrenergic agent and acetaminophen be coincident. The
      mechanism of potentiation of carbon tetrachloride hepatotoxicity is uncertain but
      clearly does not involve hepatic glutathione content. In contrast to
      acetaminophen, adrenergic effects must occur within a time window a few hours
      after the carbon tetrachloride dose for potentiation to occur. The importance of
      dose timing has not been evaluated for adrenergic potentiation of methylphenidate
      hepatotoxicity, but it is clear that this interaction is based on yet a third
      mechanism. While only three hepatotoxicants of the group I type have been
      examined in detail, the diversity of receptor types and mechanisms involved
      suggest that this phenomenon may be relevant for a wide variety of hepatotoxic
      drugs and chemicals. This interaction is also of interest because factors or
      events that lead to increased adrenergic stimulation are common in everyday life.
      Most over-the-counter cold and allergy preparations contain sympathomimetic
      drugs, and many prescription drugs produce adrenergic effects as either an
      extension of the intended therapeutic effect or as a side effect. Stress and some
      disease states can also lead to significant increases in peripheral adrenergic
      activity, creating the potential for increased susceptibility to hepatic injury
      from exposure to certain drugs or chemicals. Cocaine and bromobenzene represent
      group II, chemicals whose hepatotoxicity is diminished by cotreatment with
      adrenergic antagonist drugs. In the case of cocaine, adrenergic antagonist
      cotreatment was capable of reducing serum alanine aminotransferase activities by
      approximately 50%. For bromobenzene, the protection afforded by adrenergic
      antagonist cotreatment was more profound, with minimal hepatic lesions resulting
      from doses of bromobenzene that otherwise produced lethal hepatic necrosis. For
      the chemicals in group II, experimental observations are consistent with a
      phenomenon in which adrenergic potentiation of toxicity is supplied by the
      hepatotoxicant itself. Both cocaine and bromobenzene, in hepatotoxic doses
      increase endogenous catecholamine levels. When the effects of the elevated
      catecholamines are removed with the appropriate adrenergic antagonist, much lower
      toxicity (presumably due only to the direct hepatotoxic effects of the drug or
      chemical) is obse

PMID- 9187525
TI  - Cationic lipophilic drugs: mechanisms of action, potential consequences, and
      reversibility.

PMID- 9187526
TI  - Hepatic circulation and toxicology.

PMID- 9187527
TI  - Hepatoprotection by agents which modulate macrophage activity may be mediated by
      their mitogenic properties.

PMID- 9187528
TI  - Human cytochrome P450 enzymes: a status report summarizing their reactions,
      substrates, inducers, and inhibitors.

PMID- 9187529
TI  - Mortality associated with selegiline in Parkinson's disease. What do the
      available data mean?
AB  - A recent study by the Parkinson's Disease Research Group of the United Kingdom
      revealed higher mortality in patients with Parkinson's disease who were treated
      with selegiline (deprenyl) compared with those who were not. In this article, the
      methodological limitations of the UK study are discussed. Although several
      problems exist with this study, the mortality rate was correct, since the data
      were obtained from a verifiable source. The question then is whether or not the
      higher mortality rate can be ascribed to selegiline. It is difficult to find
      answers to this question in the study data, and we will have to wait for the
      study authors' final report. No other studies have reported higher mortality with
      selegiline. However, when prescribing selegiline in patients with early-stage
      Parkinson's disease, it is important to provide them with all the available
      information so that treatment decisions can be made jointly. Meanwhile, the best
      indication for selegiline appears to be motor fluctuations in patients with
      moderately advanced Parkinson's disease.

PMID- 9187530
TI  - Airway subsensitivity with long-acting beta 2-agonists. Is there cause for
      concern?
AB  - Regular treatment with both long- and short-acting beta 2-agonists results in
      tolerance to their bronchoprotective effects, although the relevance of this
      phenomenon in terms of long term asthma control remains unclear. However, there
      appears to be no appreciable difference between the 2 long-active beta 2
      agonists, salmeterol and formoterol, in their propensity to induce beta 2
      adrenoceptor down-regulation and subsensitivity. The degree of subsensitivity
      appears to be somewhat greater with indirect stimuli such as exercise and
      allergen challenge, compared with direct stimuli such as histamine and
      methacholine. This loss of functional antagonism with long-acting beta 2-agonist
      therapy is partial and is not prevented by concomitant inhaled corticosteroid
      therapy. However, the protective effects of inhaled corticosteroids on their own
      appear to be additive to those of long-acting beta 2-agonists when both drugs are
      concomitantly administered in the long term. The subsensitivity to
      bronchoprotection may be of clinical relevance in terms of patients who are
      inadvertently exposed to indirect bronchoconstrictor stimuli such as allergens or
      exercise, suggesting that long-acting beta 2-agonists should not be taken on a
      regular basis for this particular indication. There is a greater tendency for
      bronchodilator subsensitivity to develop with longer-acting, than with shorter
      acting beta 2-agonists, and this may reflect the longer duration of beta 2
      adrenoceptor occupancy and consequent downregulation. As with the
      bronchoprotective effects of long-acting beta 2-agonists, the development of
      bronchodilator subsensitivity is only partial and occurs regardless of whether
      patients are taking concomitant inhaled corticosteroid therapy. The long-term
      bronchodilator action of the long-acting beta 2-agonist itself is maintained
      within the twice daily administration interval. However, subsensitivity occurs in
      relation to a blunted response to repeated doses of short-acting beta 2-agonists,
      as in the setting of an acute asthma attack. There is considerable inter
      individual variability in the propensity for downregulation and subsensitivity,
      which is determined by genetic polymorphism of the beta 2-adrenoceptor. Current
      international asthma management guidelines suggest that long-acting beta 2
      agonists should be used on a regular basis in patients who ware inadequately
      controlled on inhaled corticosteroid therapy, so the addition of long-acting beta
      2-agonist therapy is an alternative to using higher doses of inhaled
      corticosteroids. There are, however, concerns that regular long-acting beta 2
      agonists might result in masking of inadequately treated inflammation in patients
      receiving suboptimal inhaled corticosteroid therapy. Physicians should be aware
      of the airway subsensitivity that develops with long-acting beta 2-agonist
      therapy, and patients should be warned that they may have to use higher than
      conventional dosages of short-acting beta 2-agonists to relieve acute
      bronchoconstriction in order to overcome this effect. In patients receiving an
      optimised maintenance dose of inhaled corticosteroid, if long-acting beta 2
      agonists are to be used on an as required basis, it would seem rational to use
      formoterol for this purpose, due to its faster onset of action than salmeterol.

PMID- 9187531
TI  - Ketorolac for postoperative pain management in children.
AB  - Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic
      effects and a relatively low incidence of adverse effects. Numerous clinical
      trials of postoperative pain treatment in children have shown that ketorolac is
      as effective as the major opioid analgesics, such as morphine, and more effective
      than codeine. The pharmacokinetics of ketorolac differ in children compared with
      adult patients after surgery. In children, the volume of distribution (Vd) of
      ketorolac is increased by as much as 2-fold relative to that in adults. The
      plasma clearance (CL) of ketorolac is also higher in children, probably because
      of lower binding to plasma proteins. However, the elimination half-life (t 1/2
      beta) of ketorolac is similar in children and adults because t 1/2 beta is
      directly proportional to Vd but inversely proportional to CL. These
      pharmacokinetic differences indicate that a higher relative dosage is required in
      children, but the dosage interval is similar in children and adults. Ketorolac
      can be administered intravenously, intramuscularly or orally. The intravenous
      route is preferred during the immediate postoperative period, until the patient
      can tolerate oral medication. Intramuscular injections are not recommended in
      children, unless the intravenous route is unavailable. The recommended
      intravenous dosage of ketorolac in children is 0.5 mg/kg, followed either by
      bolus injections of 1.0 mg/kg every 6 hours or an intravenous infusion of 0.17
      mg/kg/h. The maximum daily dosage is 90mg, and the maximum duration of treatment
      is 48 hours. The recommended oral dosage is 0.25 mg/kg to a maximum of 1.0
      mg/kg/day, with a maximum duration of 7 days. Older children may require somewhat
      lower dosages, while infants and young children may require slightly higher
      dosages to achieve the same level of pain relief. Ketorolac is not recommended
      for use in infants aged < 1 year. Unlike opioid analgesics ketorolac does not
      depress ventilation, and is not associated with nausea and vomiting, urinary
      retention or sedation. When combined with an opioid, ketorolac exhibits marked
      opioid-sparing effects, allowing a lower dosage of opioid to be used. Clinical
      studies in children and adults show that the synergistic action of ketorolac and
      opioids improves the degree and quality of pain relief, and reduces the incidence
      of opioid-related adverse effects such as respiratory depression, nausea/vomiting
      and ileus. Recovery of bowel function after abdominal surgery occurs sooner in
      ketorolac-compared with opioid-treated patients. Ketorolac reversibly inhibits
      cyclo-oxygenase, and decreases the hypersensitisation of tissue nociceptors that
      occurs with surgery. It also has reversible antiplatelet effects, which are
      attributable to the inhibition of thromboxane synthesis. Bleeding time is usually
      slightly increased, but in most patients it remains within normal values. There
      is conflicting evidence of the potential for increased surgical-site bleeding
      after tonsillectomy but, for other types of paediatric surgery, numerous clinical
      studies have confirmed that ketorolac is not associated with increased bleeding.
      Thus, ketorolac is well suited for the treatment of postoperative pain in
      children, either alone or in combination with opioids or local anaesthetics,
      because of its analgesic potency and relatively low incidence of adverse effects.

PMID- 9187533
TI  - Asthma treatment during pregnancy. What can be safely taken?
AB  - 'Safe' pharmacological therapy for gestational asthma is defined as therapy
      during which the apparent risks of the drug appear to be lower than the maternal
      and potential fetal risks of uncontrolled asthma that could result if the drug
      were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which
      can be attributed to medication in general. Information regarding the effects of
      drugs administered during pregnancy may come from animal studies, human case
      reports, and prospective cohort studies. Based on a review of the available
      information, it is recommended that mild asthma during pregnancy be managed with
      inhaled beta 2-agonists, as required; step therapy for moderate asthma would
      include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone
      dipropionate and oral theophylline. Severe gestational asthma should be treated
      with oral corticosteroids at the lowest effective dosage. The pharmacological
      management of acute asthma during pregnancy should include nebulised beta 2
      agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous
      aminophylline would not generally be recommended, unless the patient requires
      hospitalisation. Optimal medical practice medico-legal considerations demand that
      the patient's informed consent be obtained for that recommended gestational
      management programme.

PMID- 9187534
TI  - Potent and selective aromatase inhibitor: in vitro and in vivo studies with s
      triazine derivative SEF19.
AB  - We found a potent aromatase inhibitor through the screening of agents for
      estrogen-dependent breast cancer. SEF19 (2-(imidazol-1-yl)-4,6-dimorphorino-1,3,5
      triazine) decreased 50% of human placental aromatase activity in vitro at the
      concentration of 5.3 nM. In order to clarify the selectivity of SEF19 for enzyme
      inhibition, we determined the effect of SEF19 on the activities of four
      steroidogenic cytochrome P450 enzymes in porcine adrenal gland, P450SCC(side
      chain cleavage of cholesterol), P450(11 beta) (11 beta-hydroxylase), P450(17
      alpha)(17 alpha-hydroxylase/C17,20 lyase) and P450C21 (21-hydroxylase). SEF19
      failed to inhibit the activities of porcine adrenal P450SCC, P450(17 alpha) and
      P450C21 up to the concentration of 100 microM and showed some inhibition on
      P450(11 beta) activity at 100 microM, while SEF19 completely nullified the
      aromatase activity at 1 microM. We also determined the potency of SEF19 for the
      suppression of aromatase activity in vivo. SEF19 suppressed dose-dependently the
      uterine hypertrophy of immature rats caused by administration of androstenedione
      (30 mg/kg, s.c.). The ED50 of SEF19 for the suppression of uterine hypertrophy
      was 0.8 mumol/kg. These results suggest that SEF19 may serve as a potent and
      selective agent for the treatment of estrogen-dependent breast cancer.

PMID- 9187532
TI  - A rational approach to treating hypercholesterolaemia in children. Weighing the
      risks and benefits.
AB  - Because atherosclerosis is a continuous process throughout life, expert panels
      have suggested guidelines to reduce the risk of cardiovascular disease, starting
      from childhood. The guidelines focus on population-based measures and on treating
      hypercholesterolaemia in individual children. Low-fat diets in children have been
      widely debated. There is little evidence that growth is stunted or that
      nutritional deficiencies arise if the energy that is lost by limiting fat intake
      is substituted with other nutrients. Dietary fibre, plant sterols and fish oils
      have been used to modify lipid levels in children; however, the efficacy of these
      dietary adjuncts is limited. Bile acid-binding resins are the only approved drugs
      to lower cholesterol levels in children and appear to be well tolerated. However,
      compliance with resins is low because of unpalatability, so low dosages are
      preferred and vitamin supplementation is prudent. Data on HMG CoA reductase
      inhibitors and fibrates are insufficient to recommend these drugs at present.
      Drug treatment should be restricted to children who are at exceptionally high
      risk of disease, usually those with genetic dyslipidaemias.

PMID- 9187536
TI  - Acetyl-L-carnitine effects on nerve conduction and glycemic regulation in
      experimental diabetes.
AB  - Acetyl-L-Carnitine (ALC), an activator of carnitine, can accelerate nerve
      regeneration after experimental surgical injury in rats. In this study, we
      examined the ability of ALC to improve nerve conduction velocity and its effect
      on intravenous glucose tolerance test in streptozotocin-induced diabetic rats.
      Diabetic (blood glucose > 200 mg%) and normal animals were treated
      intraperitoneally for four weeks with ALC, 50 mg/Kg/d and 150 mg/Kg/d. Nerve
      conduction velocity was measured by direct exposure of sural nerve. Two-hour
      IVGTT was studied by measuring plasma glucose, insulin and free fatty acids after
      intravenous injection of glucose, 1.75 gm/Kg/body weight in animals treated
      either with ALC 150 md/Kg/d or saline alone. Six weeks of STZ-induced diabetes
      resulted in impairment of nerve conduction velocity in animals injected with
      saline (16.05 +/- 1.09 m/s), as compared to saline-treated normals who did not
      receive streptozotocin (31.0 +/- 0.84 m/s, p<0.0005). Diabetic animals treated
      with ALC, 150 mg/Kg/d, preserved near normal nerve conduction (27.10 +/- 1.42
      m/s), compared with the saline-treated diabetic animals (p < 0.0005), but
      diabetic animals treated with ALC, 50 mg/Kg/d, had a non-significant increase in
      nerve conduction (23.68 +/- 1.6). ALC treatment had no effect on fasting or post
      intravenous plasma glucose in normal or diabetic rats, although it moderately
      reduced baseline and 40 minute insulin levels (p < 0.02) in normal rats as
      compared with their saline-treated counterparts. ALC treatment lowered baseline
      free fatty acids in normal (p < 0.04) and diabetic (p < 0.03) animals, and the 60
      minute levels in the normal group only (p < 0.003). CONCLUSION: ALC at a dose of
      150 mg/Kg/d given for one month, produced near normalization of nerve conduction
      velocity in streptozotocin-induced diabetes with no adverse effects on glucose,
      insulin or free fatty acid levels.

PMID- 9187535
TI  - Involvement of arachidonic acid and the lipoxygenase pathway in mediating
      luteinizing hormone-induced testosterone synthesis in rat Leydig cells.
AB  - Evidence has been introduced linking the lipoxygenase products and
      steroidogenesis in Leydig cells, thereby supporting that this pathway may be a
      common event in the hormonal control of steroid synthesis. On the other hand, it
      has also been reported that lipoxygenase products of arachidonic acid (AA) may
      not be involved in Leydig cells steroidogenesis. In this paper, we investigated
      the effects of PLA2 and lipoxygenase pathway inhibitors on steroidogenesis in rat
      testis Leydig cells. The effects of two structurally unrelated PLA2 inhibitors (4
      bromophenacyl bromide (BPB) and quinacrine) were determined. BPB blocked the LH-
      and Bt2cAMP-stimulated testosterone production but had no effect on 22(4)-OH
      cholesterol conversion to testosterone. Quinacrine caused a dose-dependent
      inhibition of LH- and Bt2cAMP-induced steroidogenesis. The effects of different
      lipoxygenase pathway inhibitors (nordihydroguaiaretic acid (NDGA), 5,8,11,14
      eicosatetraynoic acid (ETYA), caffeic acid and esculetin) have also been
      determined. Both NDGA and ETYA inhibited LH- and Bt2cAMP-stimulated steroid
      synthesis in a dose-related manner. Furthermore caffeic acid and esculetin also
      blocked the LH-stimulated testosterone production. Moreover, exogenous AA induced
      a dose-dependent increase of testosterone secretion which was inhibited by NDGA.
      Our results strongly support the previous concept that the lipoxygenase pathway
      is involved in the mechanism of action of LH on testis Leydig cells.

PMID- 9187537
TI  - Glucocorticoid effects on the skeletal muscle differentiation program: analysis
      of clonal proliferation, morphological differentiation and the expression of
      muscle-specific and regulatory genes.
AB  - We examined the effect of glucocorticoids on the proliferation and
      differentiation of skeletal muscle cells using the C2C12 cell line. We found that
      treatment with glucocorticoids enhanced muscle cell differentiation but had only
      minor effects on the clonal growth rate of C2C12 cells. The stimulatory effect of
      glucocorticoids on myogenic differentiation was reflected in the increased
      expression of muscle-specific genes, creatine kinase (CK) and acetylcholine
      receptor gamma subunit (AChR). Dexamethasone had no effect on CK and AChR mRNA
      stability and enhanced transcription from a CAT reporter genes containing the
      3.3kb 5' flanking region of the murine CK gene (-3300MCK-CAT). Since
      dexamethasone did not affect the expression levels of the myogenic regulatory
      genes such as myoD and myogenin, the enhancement of muscle-specific transcription
      might reflect an increase in the functional activity of the regulatory proteins.
      Other possible mechanisms involved in the differentiation-enhancing effect of
      glucocorticoids are discussed.

PMID- 9187538
TI  - Identification of a CG/LH binding site in two strains of Mycobacterium vaccae.
AB  - We have previously reported the presence of a chorionic gonadotropin-like (CG
      like) protein in the bacterium Xanthomonas maltophilia (X. maltophilia). We have
      also shown that X. maltophilia possesses a unique binding site for the native
      ligand and hCG, but not for human luteinizing hormone (hLH), and that binding of
      the native ligand or hCG to the receptor causes changes in the growth rates of
      culturing X. maltophilia. In this study we have characterized a CG/LH binding
      site in two strains of Mycobacterium vaccae. The binding site is specific for hCG
      and hLH, and Scatchard analysis reveals a biphasic, high affinity binding
      pattern. This is the second identified bacterial species to possess a CG-specific
      binding site.

PMID- 9187540
TI  - CD5 B cells in autoimmune and non immune-mediated thyroid dysfunctions.
AB  - In a previous study we demonstrated a significant increase of CD5+ B subset in
      patients with Graves' disease (GD) compared with normal controls. The aim of this
      study was to compare the percentage of CD5+ B and CD5- B cells in GD with that in
      different forms of autoimmune and non immune-mediated thyroid diseases. Seventy
      two patients were studied: 28 patients with GD, 20 with silent thyroiditis (ST),
      12 with Hashimoto's disease (HD), and 12 subjects affected by hyperthyroidism due
      to toxic adenoma (TA). Eleven out of 28 patients with GD were also evaluated
      after six months of methimazole treatment. The study was performed by cytometric
      analysis. In GD the percentage and the absolute number of CD5+ B cells were
      significantly increased compared with normal controls (42.5 +/- 18.2% versus 19
      +/- 6.3%, p < 0.0001; 142 +/- 153.3/cmm versus 46.9 +/- 22/cmm, p < 0.003,
      respectively. CD5+ B cells tended to normalise after six months of treatment. In
      ST the percentage of CD5+ B cells was increased (28.6 +/- 10.2%); conversely the
      absolute number was in the normal range. Patients affected by HD did not show any
      significant modification in B cells and their subsets in comparison with
      controls. In TA, CD5+ B were 7.6 /- 4.4% and 14.3 /- 10.9/cmm. Our results
      demonstrated a marked increase in both percentage and absolute number of CD5+
      cells, only in active GD. The expansion of CD5+ B cells could play a role in the
      immune imbalance present in this disease.

PMID- 9187539
TI  - Administration of long-term estradiol and progesterone followed by progesterone
      withdrawal does not alter the plasma oxytocin secretory response to
      cholecystokinin or the pituitary oxytocin content in ovariectomized rats.
AB  - The hormone oxytocin (OT) is important for several pre- and postpartum events,
      including uterine contractions at parturition, the induction of maternal
      behavior, and milk ejection during nursing. During late pregnancy, OT mRNA is
      increased in the paraventricular nucleus (PVN) due to high estrogen and declining
      progesterone levels. Administration of sequential estrogen and progesterone to,
      followed by withdrawal of progesterone from, an ovariectomized rat also increases
      OT mRNA. However, pituitary OT peptide is not affected. In the present
      experiment, we determined if this steroid exposure alters peripheral OT secretion
      during a provocative stimulus to OT release, such as cholecystokinin (CCK). Adult
      ovariectomized Sprague-Dawley rats were implanted on day 1 with either estrogen
      or empty silastic capsules, on day 3 with progesterone or empty capsules, and on
      day 14 progesterone or empty capsules were removed. Forty-eight hrs after removal
      of the progesterone capsules, plasma OT was measured before and after i.v.
      injection of 10 micrograms/kg of CCK. At the completion of the study, pituitary
      glands were removed and OT peptide was measured. No significant differences were
      found between the sham and hormone-treated animals either in their basal or CCK
      stimulated plasma OT levels or their pituitary content of OT peptide. Although
      sequential exposure to estradiol and progesterone followed by withdrawal of
      progesterone has been shown previously to increase PVN OT mRNA, neither pituitary
      OT immunoreactivity nor basal and CCK-stimulated release of plasma OT is affected
      by this treatment. Although the mechanism of this steroid effect is not yet
      understood, our observations suggest a unique action of gonadal steroids upon PVN
      OT neurons.

PMID- 9187541
TI  - Effects of estrogen on cell growth and fibroblast growth factor receptor
      induction in MtT/Se cells.
AB  - The effects of estradiol (E2) on cell growth and the expression of fibroblast
      growth factor receptor (FGFR) were investigated in a cultured rat anterior
      pituitary cell line (MtT/Se) established from an E2-induced mammotropic pituitary
      tumor. E2 stimulated cell growth 2-3 fold as compared to the control. Basic
      fibroblast growth factor (bFGF) stimulated cell growth in the presence of E2 (10(
      9) M) but not in the absence of E2. Tamoxifen as an antiestrogen agent inhibited
      the proliferation of MtT/Se cells which had been treated with E2 or E2 and bFGF.
      Numbers of FGFR in E2-stimulated MtT/Se cells significantly exceeded those in
      cells not treated with E2. These observations indicate that E2 plays an important
      role in the regulation of FGFR induction in the anterior pituitary cells.

PMID- 9187543
TI  - Quantitative analysis of rat thyroglobulin messenger RNA in FRTL-5 cells by
      competitive polymerase chain reaction with human thyroglobulin messenger RNA.
AB  - To measure relative expression level of mRNA in a small number of cultured rat
      thyroid cells (FRTL-5), we developed a system of a quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) assay. Human thyroglobulin mRNA
      in total RNA extracted from a human thyroid tissue was used as an internal
      control. FRTL-5 cells in a 24 well dish were lysed with denaturing solution
      containing human RNA. Total RNA was extracted followed by reverse transcription
      and polymerase chain reaction. After digestion with a restriction enzyme, PCR
      products were separated by electrophoresis and stained with Sybr Green I, then
      their fluorescence was measured with fluorescent image analyser. Increase of
      thyroglobulin mRNA in FRTL-5 cells stimulated by thyroid stimulating hormone
      (TSH) was observed by this technique. Because this method does not require a
      large number of cells or radioactive isotopes, it is as useful for the analysis
      of the relative expression level of mRNAs in the cells as the conservative
      methods such as Northern Blot.

PMID- 9187542
TI  - Discrimination ability of pyridinoline crosslinks related markers for bone
      resorption in postmenopause and osteoporosis.
AB  - We investigated the discrimination ability of pyridinolines crosslinks related
      bone resorption markers. Amino-terminal pyridinolines crosslinked telopeptides
      (NTx) and carboxy-terminal pyridinolines crosslinked telopeptides (ICTP),
      pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in 62 premenopausal
      (PRE), 30 early postmenopausal healthy subjects (POST) and 24 vertebral
      osteoporosis patients (VX). NTx, Pyr and Dpyr was significantly higher in POST
      than in PRE. ICTP was not changed in POST compared with PRE. NTx, ICTP, Pyr and
      Dpyr were significantly higher in VX than in PRE and POST. To evaluate
      discriminatory ability of four markers, we calculated t-scores, and generated
      receiver operating characteristic (ROC) curves. In POST, NTx, Pyr and Dpyr had a
      moderate t-score, 1.8, 1.4 and 1.3, respectively. In ICTP t-score was only -0.2.
      In VX compared with POST, ICTP, Pyr and Dpyr had a high t-score, 5.9, 7.9 and
      7.5, respectively, but t-score of NTx was moderate, 3.6. The areas under ROC
      curves for NTx, ICTP, Pyr and Dpyr in POST were 75.8%, 33.8%, 78.1% and 79.5%,
      respectively. In VX, compared with POST, those for NTx, ICTP, Pyr and Dpyr were
      94.0%, 86.0%, 97.4% and 95.1%, respectively. In conclusion, NTx performed well in
      early postmenopausal status, but did not in osteoporosis. ICTP did not have
      discrimination power in postmenopause but performed well in osteoporosis. Pyr,
      Dpyr performed moderately well in postmenopause and performed well in
      osteoporosis.

PMID- 9187544
TI  - Stimulatory effect of the substance P antagonist spantide-II on aldosterone
      secretion of dispersed rat zona glomerulosa cells.
AB  - Substance P (SP) did not affect either basal or agonist-stimulated aldosterone
      production by dispersed rat zona glomerulosa (ZG) cells. In contrast, the SP
      receptor antagonist spantide-II (SPA), at 10(-8)/10(-6) M concentrations,
      markedly raised basal and 10(-9) M ACTH, but not 10(-9) M angiotensin II
      stimulated aldosterone secretion. The secretagogue effect of 10(-6) M SPA was
      annulled by SP (10(-6) M) and the protein kinase (PK)-C inhibitor Ro31-8220 (10(
      6) M), but was unaffected by the PKA inhibitor H-89 (10(-5) M). In light of these
      findings the following conclusions can be drawn: (i) SP does not exert a
      physiologically relevant direct modulatory action on aldosterone secretion of rat
      ZG cells; (ii) a receptor-independent inhibitory interaction is likely to occur
      between SP and SPA molecules; and (iii) SPA activates, through a receptor
      independent mechanism, phosphoinositide signaling pathway in rat ZG cells.

PMID- 9187546
TI  - The role of endotoxaemia in the development of renal disorders in experimental
      obstructive jaundice in rats.
AB  - In rats with 2-week obstructive jaundice the sensitivity to endotoxin was studied
      and the effect of a single dose of endotoxin on histological development in the
      kidney, liver and spleen was also investigated. We were tested the effect on
      accumulation and distribution within organs, of fibrinogen labelled with
      radioactive iodine I 125. We showed an increased sensitivity to endotoxin in
      obstructive jaundice. The cause of death in most rats was acute circulatory
      failure during the course of endotoxic shock, without clinical features of
      disseminated intravascular coagulation. In the isotope study, after endotoxin
      administration there was a specific dynamic increase of fibrinogen accumulation
      in the kidneys of rats with obstructive jaundice. We proposed, that the cause of
      the kidney changes during the course of obstructive jaundice could be the local
      activation of intrarenal coagulation.

PMID- 9187545
TI  - Octreotide in the control of post-sclerotherapy bleeding from oesophageal
      varices, ulcers and oesophagitis.
AB  - Bleeding from oesophageal varices, oesophageal ulcers or oesophagitis is
      occasionally massive and difficult to control. Octreotide, a synthetic analogue
      of somatostin lowers portal pressure and collateral blood flow including that
      through varices, increases lower oesophageal sphincter pressure, and inhibits the
      gastric secretion of acid as well as pepsin. Our current experience suggests it
      is effective in controlling acute variceal haemorrhage. Therefore we have
      examined the efficacy of octreotide in the control of post-sclerotherapy bleeding
      from oesophageal varices, oesophageal ulcers and oesophagitis. During the study
      period 77 patients experienced a significant gastrointestinal bleed (blood
      pressure < 100 mm Hg, pulse > 100 beats per min or the need to transfuse 2 or
      more units of blood to restore the hemoglobin level) following injection
      sclerotherapy of oesophageal varices. The source of bleeding was varices in 42
      patients, oesophageal ulcers in 31 and oesophagitis in 4. All patients received a
      continuous intravenous infusion of octreotide (50 micrograms/h) for between 40
      140h. If bleeding was not controlled in the first 12h after commencing octreotide
      hourly bolus doses (50 micrograms) for 24h were superimposed on the continuous
      infusion. Haemorrhage was successfully controlled by an infusion of octreotide in
      38 of the 42 patients with bleeding from varices, in 30 of 31 patients with
      oesophageal ulceration, and all patients with oesophagitis. In the 1 patient with
      persistent bleeding from oesophageal ulceration and in 2 of the 4 with continued
      haemorrhage from varices, haemostasis was achieved by hourly boluses of 50
      micrograms octreotide for 24h in addition to the continuous infusion. No major
      complications were associated with octreotide administration. The results of this
      study clearly indicate that octreotide is a safe and effective treatment for the
      control of severe haemorrhage after technically successful injection of
      sclerotherapy.

PMID- 9187547
TI  - Influence of the gut microflora and of biliary constituents on morphological
      changes in the small intestine in obstructive jaundice.
AB  - Increased amounts of intestinal endotoxin are absorbed in obstructive jaundice.
      The precise mechanism is not known but the increased absorption may arise from
      alterations in the luminal contents, in the intestinal flora, in the gut wall or
      in interactions between all three. To examine the effects of the intestinal flora
      we have compared the morphological changes in the small intestine in obstructive
      jaundice in germ free and conventional rats while the effects of bile
      constituents have been examined by addition of bile constituents to the diet of
      bile duct ligated rats. Changes in the intestine were examined, histologically,
      by enzyme histochemistry, and by transmission and scanning electron microscopy.
      The results showed no differences in response between germ free and conventional
      rats. Feeding of diets containing bile salts exacerbated the lesion. Feeding of
      diets containing cholesterol, however, reduced the degree of intestinal changes
      produced by cholestasis and completely antagonised the increase in damage caused
      by feeding of bile salts.

PMID- 9187549
TI  - Choledochoduodenostomy in the management of common duct stones or associated
      pathology--an obsolete method?
AB  - Choledochoduodenostomy (CDD) has been reported as a more effective treatment of
      CBD stones than T-tube drainage but it is regarded as a last resort or obsolete
      therapeutic method due to fears of higher mobidity, cholangitis, "sump" syndrome
      and liver dysfunction. We aimed to assess the aforementioned issues analyzing
      prospectively our experience from 1976 through Dec.92. METHODS: CDD was performed
      in 89 females and 36 males, aged 60 +/- 8.7 years, 26 during repeat surgery. Duct
      stones were the indication in 94, Sphincter of oddi (SO) dysfunction in 23 and
      obstructive pancreatitis nodule in 8. Peroperative liver biopsies were obtained
      in 44 patients. The "follow-up" schedule (> 2.5 years in 110) included clinical
      interview and LFT's on an yearly basis. Ultra sound (USG) was obtained every one
      or two years. ERC was done in 10 symptomatic patients and in 25 others for
      protocul purposes. Liver biopsies were taken four to nine years post surgery in
      11 patients-five at relaparotomy for non-biliary causes and six percutaneously by
      fine needle. Ductal mucosa biopsy could safely be performed in one patient 10
      years after surgery. The long-term results were classified as excellent, good,
      fair or poor. Poor meant the need for further invasive therapy (resurgery or
      EST). RESULTS: There were two operative deaths (1.6%). The long-term results (123
      survivors) were considered excellent in 89, good in 22, fair in 9 and poor in
      three. Three patients died from unrelated causes and eight others ceased the
      "follow-up" evaluation three to five years post surgery. All of them were
      considered as having excellent or good results. A widely patient anastomosis of
      approximately 20 mms without mucosal inflammatory changes was documented in every
      patient assessed via ERC. food "debris" was detected within the distal duct of
      four patients yet it was easily flushed through the stoma. Normal tissue patterns
      were observed in all long-term liver biopsies. Likewise the ductal mucosa biopsy
      failed to reveal any acute or chronic inflammatory changes. CONCLUSIONS: 1) CDD
      is a highly effective short and long-term treatment of CBD lithiasis.2) It does
      not lead to bacterial or "chemical" cholangitis, to "sump" syndrome or to hepatic
      dysfunction, provided a wide anastomosis is accomplished.3) CDD should only be
      considered as obsolete after extensive, long-term, prospective, randomized
      assessment of laparoscopic or combined laparoendoscopic approaches have been
      shown to be as effective as or superior to CDD.

PMID- 9187548
TI  - The relationship between portal venous and hepatic arterial blood flow. I.
      Experimental liver transplantation.
AB  - The relationship between the changes in portal venous and hepatic arterial blood
      flows, in the liver is a much disputed question, it has tremendous significance
      in the practice of transplantation, and an explanation has been available since
      1981, when Lautt published the so-called "adenosine washout theory". According to
      our earlier observations the decrease of portal pressure or flow consistently led
      to an increase in hepatic artery flow. At the same time changes in hepatic artery
      flow or pressure seemed to produce only inconsistent effects on the portal
      circulation. In the present experiments liver transplantation (OLTX) was carried
      out on mongrel dogs by Starzl's method. Electromagnetic flow probes were placed
      on the hepatic artery and the portal vein before removal of recipient's liver,
      and after completion of all vascular anastomoses to the newly inserted liver,
      during the recirculatory phase of OLTX. The flow probes were connected to a
      Hellige electromagnetic flowmeter, portal venous and systemic arterial pressures
      were also recorded. The control HAF was 241 +/- 23 ml/min, the average PVF was
      517 +/- 47 ml/min before removal of the recipient's liver. In the recirculatory
      phase of HAF increased, by 71 +/- 12% (p < 0.001). The PVF decreased in most
      animals after OLTX. The decrease was in average -40.2 +/- 3.5% (p < 0.001). The
      THBF calculated by adding the HAF and PVF showed a small, but not significant
      decrease recirculation. The systemic arterial pressure decreased slightly and
      portal vein pressure rose in most animals after OLTX. There was a substantial
      increase in portal inflow resistance and prehepatic arteriolar resistance and a
      decrease in hepatic artery resistance. The decrease of PVF after OLTX can be
      explained by progressive fluid accumulation in the liver parenchyma and increased
      sinusoidal and portal inflow resistance. The prolonged and continuous increase in
      hepatic artery flow during the recirculatory phase of OLTX may be due to the
      decrease of portal flow. The exact mechanism, by which a change in portal flow
      leads to arteriolar dilatation, can be most probably explained by the "adenosine
      washout theory" of Lautt.

PMID- 9187550
TI  - Development of collaterals in intermittent and permanent ischemia of the liver.
AB  - The ischemia caused by the hepatic dearterialization as therapy for hepatic
      malignancies is transient because of the rapid formation of collaterals. In order
      to prevent this transient repeated ischemia has been suggested. An experimental
      study was planned to compare the collateral occurrence in persistent ischemia and
      transient repeated ischemia of the liver. Fourteen dogs (seven persistent
      ischemia, seven transient repeated ischemia) were used in this study. Hepatic
      dearterialization were performed in both groups. In the first group (persistent
      ischemia), the hepatic artery was ligated proximal to the gastroduodenal artery.
      In the second group (transient repeated ischemia), the hepatic artery was
      occluded externally in the same region as the first group by means of a device
      modified from 8 guage Foley catheter and after occlusion for one hour it was
      reopened. Occlusions were repeated twice in a day. Five dogs in the first group
      and six dogs in the second group completed a three week ischemia period and
      angiography were then performed in all. The dogs were sacrificed after the
      angiography and examined for possible abscess formation, arterial thrombosis,
      peritoneal adhesions and liver necrosis. After angiography, the two groups were
      also examined for collateral occurrence. Only one collateral occurred in the
      transient repeated ischemia group, but in the persistent ischemia group,
      collaterals occurred in all dogs. This difference between two groups is
      statistically significant (Fischer Absolute Chi Square Test, p = 0.013).
      Transient repeated ischemia is superior to persistent ischemia because of fewer
      collaterals, but in practise, total dearterialization of the liver is impossible.

PMID- 9187551
TI  - Carcinoid tumor of the common bile duct.
AB  - A case of primary carcinoid tumor of the common bile duct is presented.
      Diagnostic and therapeutic uncertainties of this extremely rare cause of jaundice
      are discussed.

PMID- 9187552
TI  - Squamous cell carcinoma of the liver originating from a solitary non-parasitic
      cyst case report and review of the literature.
AB  - Squamous cell carcinoma of the liver arising from a non-parasitic cyst is a rare
      entity of a primary liver tumor with an unfavourable prognosis. We report a case
      of a patient with a cyst in the right lobe leading to upper abdominal symptoms
      and respiratory discomfort. Malignancy was not suspected from the clinical
      findings or repeated cytological examination of the cyst fluid. However, the
      blood stained brown color of the cyst fluid was unusual. Cyst recurrence after
      six attempts of conservative treatment with sonography guided drainage over a
      period for more than one year led to laparotomy with cyst unroofing. Because
      frozen section from the cyst wall revealed the unexpected finding of squamous
      cell carcinoma right hemihepatectomy was performed during the same operation. The
      patient is alive more than four years after surgery without cyst or tumor
      recurrence. The difficulties in establishing diagnosis are confirmed by the
      review of other reports. In the diagnosis and treatment of symptomatic non
      parasitic liver cysts possible malignancy has to be considered. In case of proven
      carcinoma radical surgery with partial hepatectomy should be performed.

PMID- 9187553
TI  - Isolated late metastasis of a renal cell cancer treated by radical distal
      pancreatectomy.
AB  - A 53-year-old man underwent right nephrectomy for a locally renal cell carcinoma
      with concomitant resection of a solitary metastasis in the right lung. Ten years
      later, he presented with haematochezia caused by a tumour in the tail of
      pancreas, invading the transverse colon and the greater curvature of the stomach.
      The tumour was radically resected, and histological examination revealed a
      solitary metastasis of the previous renal cell carcinoma. This case illustrates a
      rare indication for pancreatic resection because of pancreatic metastasis.

PMID- 9187555
TI  - Are hepatic adenomas premalignant?

PMID- 9187554
TI  - Hepatic metastases of granulosa cells tumour of the ovary.
AB  - A case of metastatic granulosa cell tumour of the ovary is reported.
      Investigations revealed a secondary tumour in segment VI and VII of the liver.
      Right hepatic resection was performed. Microscopic findings revealed a tumour
      with histological features identical to that removed eleven years before.

PMID- 9187556
TI  - Type IVA choledochal cyst: is hepatic resection necessary?

PMID- 9187557
TI  - Interferon or corticosteroid: treatment of patients with chronic hepatitis C
      positive for serum markers of autoimmune diseases.

PMID- 9187558
TI  - Non-alcoholic steatohepatitis and GB virus-C/hepatitis G virus infection: is
      there a casual relationship?

PMID- 9187559
TI  - Lymphocytic adenohypophysitis and neurohypophysitis.

PMID- 9187560
TI  - Pulmonary diseases due to Mycobacterium kansasii in Japan.

PMID- 9187561
TI  - Significance of antigen-specific T cell clones in collagen diseases: analyses
      with a novel T cell clonality evaluation system.
AB  - The involvement of antigen-specific T cells in the pathogenesis of collagen
      diseases is still controversial. The final stages of collagen diseases are
      usually characterized by the dominance of inflammation. Therefore, antigen non
      specific factors, such as inflammatory cytokines, probably play an important role
      in this process. On the other hand, the methods available to analyze the antigen
      specific aspects of the immune response are still limited. Here we review our
      novel system of T cell clonality analysis based on the idea that activated
      antigen-specific T cells should form accumulating clones among the lymphocyte
      population. Using this method, dynamic changes of clonal accumulation of T cells
      could be evaluated during antigenic stimulation in vivo and in vitro. The
      significance of antigen-specific T cell clones in collagen diseases is discussed
      using data obtained from patients with rheumatoid arthritis and systemic lupus
      erythematosus.

PMID- 9187562
TI  - Does the presence of serum autoantibodies influence the responsiveness to
      interferon-alpha 2a treatment in chronic hepatitis C?
AB  - The serum autoantibodies, antinuclear antibody, anti-DNA antibody, anti-smooth
      muscle antibody, antithyroglobulin antibody, antimicrosomal antibody,
      antimitochondrial antibody, rheumatoid factor and antibody to
      deoxyribonucleoprotein were measured at the baseline and on completion of
      interferon-alpha 2a (IFN-alpha 2a) treatment in chronic hepatitis C (CHC)
      patients who did not present with any autoimmune disease prior to treatment. Of
      the 57 patients examined, 27 spontaneously manifested at least one autoantibody.
      Only the prevalence of rheumatoid factor (26%) was significantly higher in the
      CHC patients than in the control subjects. There were no differences in the
      prevalence of the 8 autoantibodies examined between hepatitis C virus (HCV)
      genotypes 1b and 2a/2b. Twenty-six patients responded to IFN-alpha 2a.
      Subclinical hypothyroidism developed in two patients with elevated antithyroid
      antibody titres during treatment. No relationship was observed between changes in
      the status of autoantibodies and either response to IFN-alpha 2a or HCV genotype.
      Irrespective of the HCV genotype, autoantibodies might be present in CHC patients
      before and during the IFN-alpha 2a treatment. The presence of such antibodies
      does not represent a contraindication to the use of IFN-alpha 2a in CHC patients
      not complicated by autoimmune diseases. Careful observations are necessary for
      CHC patients positive for antithyroid antibodies during the IFN-alpha 2a
      treatment. Preexisting or newly developed autoantibodies do not necessarily
      predict a poor response to IFN-alpha 2a.

PMID- 9187563
TI  - Severity of coronary artery calcification detected by electron beam computed
      tomography is related to the risk of restenosis after percutaneous transluminal
      coronary angioplasty.
AB  - To assess the relationship between coronary artery calcification and the late
      success rate of percutaneous transluminal coronary angioplasty (PTCA), we
      performed electron beam computed tomography (EBCT) in 22 patients with ischemic
      heart disease who underwent PTCA. The calcification score in each coronary artery
      vessel was estimated and compared with the occurrence of restenosis at 3 months
      after PTCA. Angioplasty had been performed in 28 sites in 22 patients, and 12
      sites exhibited restenosis. The mean calcium score in the unsuccessful PTCA
      vessels was significantly higher than in successful sites (228 vs 92). The
      overall late success rate of PTCA with moderate to severe calcification was
      extremely low at 29%. Coronary segments with diffuse and extensive calcification
      were not optimal target lesions for PTCA. Prediction of the late success rate
      after PTCA may be possible by prior evaluation of coronary artery calcification
      utilizing EBCT.

PMID- 9187564
TI  - Left ventricular hypertrophic patterns and wall motion dynamics in hypertrophic
      cardiomyopathy: an electron beam computed tomographic study.
AB  - To investigate the left ventricular hypertrophic patterns and wall motion
      dynamics in hypertrophic cardiomyopathy, 51 patients were studied using electron
      beam computed tomography. The subject consisted of 26 asymmetrical hypertrophy, 9
      diffuse hypertrophy, 14 apical hypertrophy and 2 papillary muscle hypertrophy.
      Concerning the wall motion dynamics in hypertrophic wall, 7 demonstrated
      homogeneous wall thickening involving the non-hypertrophic wall, 36 showed
      decrease wall thickening, 6 showed normal wall thickening, and 2 cases of
      papillary muscle hypertrophy had increased wall thickening in the apical wall.
      The percent wall thickening in hypertrophic wall was significantly reduced in
      relation to the increase of wall thickness; 14 +/- 8% in the wall over 20 mm, 23
      +/- 12% in 16-9 mm and 56 +/- 36% in 13-15 mm. The reduced wall motion dynamics
      in hypertrophic wall were clearly observed by electron beam computed tomography.

PMID- 9187565
TI  - Evoked potentials in patients with chronic respiratory insufficiency.
AB  - P300, somatosensory evoked potential (SEP) and brainstem auditory evoked
      potential (BAEP) are widely used neurophysiological methods for objectively
      evaluating cognitive, somatosensory and brainstem auditory functions. We studied
      the P300, SEP and BAEP in 17 patients with chronic respiratory insufficiency
      (PaO2:58.2 +/- 7.0 mmHg; mean +/- SD) and 15 age-matched healthy subjects (PaO2:
      84.4 +/- 11.3 mmHg). The latency and amplitude of P300, the N9 latency, N9-N13
      and N13-N20 interpeak latencies (IPL) in SEP, wave I latency and I-V IPL in BAEP
      were compared between the patients and controls. The P300 latency, N9-N13 and N13
      N20 IPLs in SEP in the patients were significantly prolonged compared to the
      controls. In contrast, the amplitude of P300, N9 latency in SEP, wave I latency
      and I-V IPL in BAEP were not significantly different between the patients and
      controls. These results suggest that chronic respiratory insufficiency influences
      the cognitive and somatosensory functions, and indicate that there is a selective
      vulnerability of evoked potentials to this condition.

PMID- 9187566
TI  - Inhibitory effects of theophylline and procaterol on eosinophil function.
AB  - Eosinophils play a crucial role in bronchial asthma. As theophylline and
      procaterol (beta 2-agonist) are used for the treatment of bronchial asthma, the
      specific functions of eosinophils in the presence of granulocyte/macrophage
      colony-stimulating factor (GM-CSF) or platelet activating factor (PAF) were
      examined using theophylline and procaterol alone and in combination. Eosinophil
      degranulation induced by PAF or GM-CSF was inhibited by theophylline (10(-6) M
      10(-3) M and 10(-6) M to 10(-3) M, respectively) and procaterol (10(-7) M-10(-5)
      M and 10(-7) M-10(-5) M, respectively). The combination of 10(-4) M theophylline
      and various concentrations of procaterol provided higher inhibition than 10(-4) M
      theophylline or procaterol (10(-7) M-10(-5) M). CD11b, which is a triggering
      molecule for human eosinophil degranulation, showed a significantly inhibited
      expression of PAF stimulation with 10(-4) M theophylline. CD11b and another
      triggering molecule for eosinophil degranulation, CD18, showed a significantly
      inhibited expression of PAF stimulation using a combination of 10(-4) M
      theophylline and various concentrations of procaterol (10(-5) M-10(-7) M)
      compared with the inhibition of 10(-4) M theophylline or procaterol (10(-5) M-10(
      7) M), but GM-CSF-stimulated eosinophils were not inhibited. Taken collectively,
      theophylline and/or procaterol have anti-inflammatory effects.

PMID- 9187567
TI  - Chronic hepatitis infected with hepatitis GB virus type C/hepatitis G virus
      presenting as non-alcoholic steatohepatitis.
AB  - A 68-year-old man with moderate liver dysfunction diagnosed with atypical
      pneumonia showed serum alanine aminotransferase and gamma-glutamyltranspeptidase
      levels which revealed a sustained abnormality over six months. Hepatitis GB virus
      type C/hepatitis G virus demonstrated in his serum by reverse transcription
      polymerase chain reaction. Liver histology showed steatohepatitis typically
      observed in alcoholic hepatitis without a remarkable drinking history. This case
      suggests that hepatitis GB virus type C/hepatitis G virus may induce chronic
      hepatitis and that there may be cases with chronic hepatitis induced by this
      virus in patients who have been diagnosed with alcoholic liver disease, even in
      cases with typical histology of alcoholic hepatitis.

PMID- 9187568
TI  - Transient hypertension due to adrenal hemorrhage in a patient with von
      Recklinghausen's disease.
AB  - A 29-year-old man with von Recklinghausen's disease suddenly developed severe
      epigastric pain and was admitted to hospital. Physical examination revealed
      elevated blood pressure (200/130 mmHg) and tachycardia (162 bpm). Initially, he
      was suspected to have appendicitis, and appendectomy was performed immediately;
      however, appendicitis was not demonstrable pathologically. Retroperitoneal
      hematoma was found incidentally during the operation. Further clinical and
      laboratory examination demonstrated a marked increase in the urinary excretion of
      catecholamines. There was no evidence of pheochromocytoma on computed tomography
      or magnetic resonance imaging; however, these imaging studies simply showed a
      hematoma at the right adrenal gland. Transient hypertension and tachycardia,
      resembling pheochromocytoma, was caused by adrenal hemorrhage.

PMID- 9187569
TI  - A candidate case for lymphocytic infundibulo-neurohypophysitis mimicking a
      neurohypophysial tumor.
AB  - A 56-year-old Japanese man presented with a 2-month duration of polyuria and
      polydipsia. The diagnosis of diabetes insipidus was confirmed by water
      deprivation and vasopressin injection. The secretory function of the
      adenohypophysis was estimated as normal by a variety of provocative tests.
      Magnetic resonance imaging (MRI) displayed the loss of the hyperintense signal of
      the neurohypophysis and a tumor-like lesion confined to the neurohypophysis. The
      tissue specimen resected at transsphenoidal surgery showed diffuse lymphocytic
      infiltration. These findings suggest that this is a candidate case for
      lymphocytic infundibuloneurohypophysitis (LIN) that is not identical to classical
      lymphocytic hypophysitis. This patient will be followed up to determine whether
      this case simply represents an early stage of classical hypophysitis or a
      different clinical entity.

PMID- 9187570
TI  - Fatal pulmonary infection due to multidrug-resistant Mycobacterium kansasii which
      developed in an immunocompetent young man.
AB  - A 32-year-old immunocompetent man developed fever and malaise that persisted for
      three years. As he had no health insurance, he never received any medical
      treatment. On admission, chest X-ray revealed multiple cavitary lesions and his
      sputnum yielded acid-fast bacilli, that were identified as Mycobacterium kansasii
      with multidrug resistance. Although his general status improved transiently by
      antituberculous agents, he died of respiratory insufficiency after four months.
      The prognosis of Mycobacterium kansasii pulmonary disease is reported to be
      relatively good among non-tuberculous mycobacteriosis, however, physicians must
      pay careful attention to cases of delayed start of therapy or multidrug
      resistance, or both.

PMID- 9187571
TI  - Oculomotor nerve palsy caused by lung cancer metastasis.
AB  - A 39-year-old man with a known diagnosis of lung adenocarcinoma developed
      intermittent double vision with right pupil dilatation. His symptoms eventually
      progressed to complete oculomotor nerve palsy on the right. Postmortem
      examinations revealed a metastasis of the adenocarcinoma involving the root of
      right oculomotor nerve.

PMID- 9187572
TI  - Angiotropic lymphoma diagnosed by muscle biopsy.
AB  - On hospitalization, the clinical examination of a 64-year-old female with
      polyarthralgia and an elevated fever revealed leukocytosis, an increased lactic
      acid dehydrogenase level, and a positivity for the C-reactive protein.
      Subsequently, the patient developed muscular pain in the lower limbs. Thus, a
      muscle biopsy was performed and B-cells with atypia were detected in the
      arteriolar lumen within the muscle. This led to the diagnosis of angiotropic
      lymphoma (AL). A combination chemotherapeutic regimen was initiated, and the
      patient's symptoms disappeared. AL is difficult to diagnose before death, but in
      this case, muscle biopsy facilitated an early diagnosis and subsequent
      chemotherapy resulted in the disappearance of the AL. We thus feel this report
      may be of value.

PMID- 9187573
TI  - Stiff-man syndrome associated with antecedent myasthenia gravis and organ
      specific autoimmunopathy.
AB  - We describe a case of stiff-man syndrome accompanied by diabetes mellitus,
      Hashimoto's thyroiditis and the antecedent myasthenia gravis. The diagnosis of
      stiff-man syndrome was made based on not only clinical findings and the
      characteristic electromyographic pattern but also the presence of antibodies to
      glutamic acid decarboxylase in the serum and cerebrospinal fluid. Stiff-man
      syndrome is known to be associated with organ-specific autoimmunopathy including
      insulin-dependent diabetes mellitus. The present case is the first one that stiff
      man syndrome was preceded by myasthenia gravis of organ-specific autoimmunopathy.
      Stiff-man syndrome in the present case probably represents the one of fully
      expressed manifestations from the broad spectrum of organ-specific
      autoimmunopathy caused by the loss of self-tolerance.

PMID- 9187574
TI  - Amyotrophic lateral sclerosis with anti-acetylcholine receptor antibody.
AB  - We report a case of amyotrophic lateral sclerosis (ALS) with anti-acetylcholine
      receptor (AChR) antibody in a 73-year-old female patient. She showed the typical
      course of ALS. She had no clinical findings of myasthenia gravis and had never
      undergone neurotoxin therapy using snake venom. Anti-AChR antibody was positive
      with a titer of 0.50 nmol/l on admission. We traced the titers during the
      progression of ALS; the titer was positive when muscle weakness worsened, and it
      became negative when the general condition became stable. We suppose that the
      occurrence of anti-AChR antibody may be partially relevant with abnormalities at
      the neuromuscular junction during the progression of ALS.

PMID- 9187575
TI  - Hispanic Health and Nutrition Examination Survey: methodological considerations.
AB  - The Hispanic Health and Nutrition Examination Survey (HHANES) was the first
      special population survey undertaken by the National Center for Health
      Statistics. The HHANES was designed to assess the health and nutritional status
      and needs of Mexican Americans, mainland Puerto Ricans and Cuban Americans. Data
      were collected using five data collection techniques: direct physical
      examinations, diagnostic testing, anthropometry, laboratory analyses, and
      interviews. Unlike other surveys conducted by the National Center for Health
      Statistics, the HHANES was not designed as a national survey. The HHANES was a
      survey of three Hispanic subgroups of the population in selected areas of the
      United States with a survey universe that included approximately 76 percent of
      the 1980 Hispanic-origin population in the United States. This article discusses
      statistical issues that should be addressed by researchers when analyzing HHANES
      data. Specifically, analysts need to account for the complex sample design,
      nonresponse bias, potential non-coverage bias, and the regional nature of the
      HHANES sample.

PMID- 9187576
TI  - Acculturation, access to care, and use of preventive services by Hispanics:
      findings from HHANES 1982-84.
AB  - Use of preventive health services (physical, dental, and eye examinations, Pap
      smear and breast examinations) among Mexican American, Cuban American, and Puerto
      Rican adults (ages 20-74) was investigated with data from the HHANES. Analyses
      focused on the relative importance of two predictors of recency of screening:
      access to services (health insurance coverage, having a routine place for care,
      type of facility used, having a regular provider, travel time) and acculturation
      (spoken and written language, ethnic identification). Regression analyses
      controlling for age, education, and income indicated that utilization of the
      preventive services was predicted more strongly by access to care than by
      acculturation. For each Hispanic group, having a routine place for health care,
      health insurance coverage, and a regular provider were each significantly
      associated with greater recency of screening. Type of facility used and travel
      time produced less consistent effects. These results replicate past studies that
      have demonstrated the important link between institutional access and use of
      health services. Of the acculturation variables, language but not ethnic
      identification (which was measured only for the Mexican Americans) predicted use.
      This latter finding, which has been demonstrated in other studies as well,
      suggests that the effect of language on screening practices should not be
      interpreted as a cultural factor, but as an access factor, i.e. use of English
      favors access to services.

PMID- 9187577
TI  - Health risk behaviors of Hispanics in the United States: findings from HHANES,
      1982-84.
AB  - With data from the Hispanic Health and Nutrition Examination Survey (HHANES), we
      examined several health risk behaviors (cigarette smoking, alcohol use, dietary
      practices, and recency of health screening) of Mexican American, Cuban American,
      and Puerto Rican adults (ages 20-74). For each sample, a greater percentage of
      men than women smoked cigarettes and used alcohol. Heavy smoking (20+ cigarettes
      per day) was most prevalent for Cuban American males, and heavy drinking (1.00+
      oz ethanol per day) was most prevalent for Mexican American and Puerto Rican men.
      Acculturation correlated positively with alcohol use (particularly for females)
      and negatively with dietary balance (for Mexican American men and women). The
      Puerto Ricans' diet was less balanced than that of the other two groups. For each
      sample, more men than women had not had a routine physical or dental examination
      within the past five years; the recency of screening was lowest for Mexican
      American men. Screening (including Pap smear for the women) was lower for those
      who smoked cigarettes and for those with poor dietary practices, indicating that
      many Hispanics at special risk of disease underutilize preventive health
      services, increasing the likelihood of diagnosis at a later stage of illness.

PMID- 9187578
TI  - Health care utilization barriers among Mexican Americans: evidence from HHANES
      1982-84.
AB  - Data from the Hispanic Health and Nutrition Examination Survey (HHANES) conducted
      by the National Center for Health Statistics in 1982-1984 were analyzed to
      document the type of barriers encountered which prevented Mexican Americans from
      obtaining health care, the sociodemographic subgroups most vulnerable to such
      barriers, and to examine the combined effects of predisposing, enabling, and need
      characteristics on these barriers. The findings suggest, in general, that low
      income groups, younger age groups, the less acculturated, those who lack health
      insurance coverage, those with functional limitations, and those in poorer
      perceived health status encounter more barriers than others, and are prevented by
      these barriers from obtaining health care for themselves.

PMID- 9187579
TI  - Utilization of curanderos by Mexican Americans: prevalence and predictors.
      Findings from HHANES 1982-84.
AB  - Data from the Southwest sample of the Hispanic Health and Nutrition Examination
      Survey (HHANES) were analyzed to examine whether the use of a curandero or other
      folk medicine practitioner hindered, enhanced, or did not affect the utilization
      of western health care services by Mexican Americans. Findings revealed that only
      4.2 percent of the HHANES sample persons between the ages of 18-74 years reported
      consulting a curandero, herbalista, or other folk medicine practitioner within
      the 12 months prior to the survey. Income, self-perceived health status, the
      language of the interview, and dissatisfaction with modern medical care recently
      received independently predicted curandero utilization (adjusted OR 2.01 and
      1.66, respectively). Low income and self-perceived health status were less
      strongly related to curandero utilization.

PMID- 9187580
TI  - Alcohol consumption patterns among Mexican American mothers and among children
      from single- and dual-headed households: findings from HHANES 1982-84.
AB  - Data from the southwestern United States sample of the Hispanic Health and
      Nutrition Examination Survey were employed to compare the patterns of alcohol use
      among Mexican American mothers and children in female-headed households with use
      patterns among mothers and children in couple-headed households. Single female
      heads of household drank more alcoholic beverages on more days than females from
      dual-headed households. As a whole, the children of single heads of household
      still living at home did not demonstrate significantly different drinking
      patterns from their dual-headed household counterparts. While male children of
      single-headed households drank more days and total drinks than their dual-headed
      household counterparts, female children of dual-headed households drank more days
      and total drinks than female children from single-headed households.

PMID- 9187581
TI  - Acculturation and alcohol consumption in the Mexican American population of the
      southwestern United States: findings from HHANES 1982-84.
AB  - Data from the Southwestern sample of the Hispanic HANES are employed to evaluate
      the relationship of acculturation into the larger society with alcohol
      consumption. As in previous work, acculturation was not found to be related to
      alcohol consumption of Mexican American men, but was positively related to the
      consumption of younger Mexican American women. Among middle-aged women,
      acculturation was not important. However, we found evidence that middle-aged
      women might be turning to alcohol in response to marital disruption and poverty.
      In addition, middle-aged women who are not employed are less frequent drinkers
      but those who drink are heavier drinkers than employed women.

PMID- 9187582
TI  - Patterns of cigarette smoking among Hispanics in the United States: results from
      HHANES 1982-84.
AB  - In the 1982-84 Hispanic Health and Nutrition Examination Survey, the prevalence
      of cigarette smoking was examined among Mexican Americans, Puerto Ricans, and
      Cuban Americans in the United States. Among 20-74 years olds, the age-adjusted
      smoking rates for Mexican American, Puerto Rican, and Cuban American men were
      high--42.5, 39.8, and 41.6 percent, respectively. Quite striking among Cuban
      American men was the high smoking rate among 20-34 year olds (50.1 percent), the
      highest smoking rate in the three Hispanic groups compared. The age-adjusted
      smoking rates for Mexican American, Puerto Rican, and Cuban American women were
      much lower than those for men-23.8, 30.3, and 24.4 percent, respectively. Both
      Puerto Rican and Cuban American men were more likely to be heavy smokers (52.3
      and 64.1 percent, respectively, smoking a pack or more a day) as compared to the
      Mexican Americans (33.8 percent smoking a pack or more a day). The pattern was
      the same for women, with Mexican American women being lighter smokers (18.8
      percent smoking a pack or more a day) as compared to heavy smoking among Puerto
      Rican and Cuban American women (35.1 and 48.6 percent, respectively, smoking a
      pack or more a day). Given the health hazards of smoking, future research and
      intervention are required for those groups with high exposure to cigarette
      smoking.

PMID- 9187583
TI  - Acculturation and marijuana and cocaine use: findings from HHANES 1982-84.
AB  - We examined the relation between acculturation and illicit drug use among
      Hispanics in the United States employing data from the 1982-84 Hispanic Health
      and Nutrition Evaluation Survey (HHANES). Across all Hispanic groups,
      acculturation into US society, as reflected in English language use, was
      associated with higher rates of illicit drug use even after sociodemographic
      variables such as gender, age, income, and education were considered. Significant
      interactions between language and education indicated that the predominant use of
      English was more strongly associated with marijuana and cocaine use among Mexican
      Americans and Puerto Ricans of lower educational attainment than among those of
      higher educational attainment. Significant interactions between language use and
      other factors such as sex, marital status, and place of birth were also
      associated with marijuana and cocaine use. These results suggest that the
      experience of acculturation, especially as it relates to drug use, is closely
      tied to the social and economic context in which an individual lives.

PMID- 9187584
TI  - Generational differences in perinatal health among the Mexican American
      population: findings from HHANES 1982-84.
AB  - Data from the Hispanic Health and Nutrition Examination Survey (HHANES) were used
      to examine a profile of social, medical, and behavioral characteristics
      associated with low birth-weight (LBW) and miscarriages in first and second
      generation Hispanics of Mexican descent. The percentage of LBW was 5.3 and of
      miscarriages was 12.7. LBW rates were higher for second generation primipara and
      multipara compared with first generation women. Using multivariate logistic
      regression techniques and adjusting for complex design effects, generation was
      found to be a significant predictor of LBW but not of miscarriages. The findings
      support existing evidence that a Mexican cultural orientation protects first
      generation. Mexico-born women against a risk for LBW. However, the findings do
      not show significant effects of generation on miscarriages, suggesting that
      cultural effects are not consistent for all pregnancy outcomes. Furthermore, we
      suggest that the higher rates of LBW in second generation women are not due to a
      higher rate of miscarriages as has been hypothesized.

PMID- 9187585
TI  - The prevalence of total tooth loss, dental caries, and periodontal disease among
      Mexican Americans, Cuban Americans, and Puerto Ricans: findings from HHANES 1982
      1984.
AB  - This paper describes the prevalence of total tooth loss, dental caries, and
      periodontal disease in 2,226 Puerto Ricans, 1,192 Cuban Americans, and 5,983
      Mexican Americans, ages five to 74 years, who were examined during the 1982-84
      Hispanic Health and Nutrition Examination Survey (HHANES). The prevalence of
      total tooth loss was 2.60, 6.10, and 2.80 percent among Mexican Americans, Cuban
      Americans, and Puerto Ricans, respectively. After adjusting for the confounding
      effects of age, sex, income, and education status, no statistically significant
      differences were found in the mean number of decayed teeth among the three groups
      of Hispanics. Puerto Rican children had an average of 2.09 filled teeth compared
      with an average of 1.39 and 1.43 filled teeth for Mexican Americans and Cuban
      Americans, respectively. In adults, Puerto Ricans and Cuban Americans had at
      least 40 percent higher mean number of filled teeth than Mexican Americans. Cuban
      American and Puerto Rican adults had about twice as many missing teeth as Mexican
      Americans. The pit-and-fissure tooth surfaces in children accounted for the
      majority of sites affected by caries. All Hispanics had a higher prevalence of
      gingivitis than American adults as estimated during the 1985-86 National
      Institute of Dental Research (NIDR) survey of American adults. Puerto Ricans had
      the highest level of periodontal disease and the highest Debris Index scores
      among the Hispanic groups.

PMID- 9187586
TI  - Effects of blood transfusion on oxygen uptake: old concepts adapted to new
      therapeutic strategies?

PMID- 9187587
TI  - Gabexate mesilate prevents compression-induced spinal cord injury.

PMID- 9187589
TI  - Adverse effects of interrupting precordial compression during cardiopulmonary
      resuscitation.
AB  - OBJECTIVES: In the current operation of automated external defibrillators,
      substantial time may be consumed for a "hands off" interval during which
      precordial compression is discontinued to allow for automated rhythm analyses
      before delivery of the electric countershock. The effects of such a pause on the
      outcomes of cardiopulmonary resuscitation were investigated. DESIGN: Prospective,
      randomized, controlled animal study. SETTING: Research laboratory. SUBJECTS: Male
      Sprague-Dawley rats. INTERVENTIONS: Ventricular fibrillation was electrically
      induced in 25 Sprague-Dawley rats. After 4 mins of untreated ventricular
      fibrillation, precordial compression was begun and continued for 6 mins. Animals
      were then randomized to receive an immediate defibrillation shock or the
      defibrillation attempt was delayed for intervals of 10, 20, 30, or 40 secs.
      MEASUREMENTS AND MAIN RESULTS: Immediate defibrillation restored spontaneous
      circulation in each instance. When defibrillation was delayed for 10 or 20 secs,
      spontaneous circulation was restored in three of five animals in each group.
      After a 30-sec delay, spontaneous circulation was restored in only one of five
      animals (p < .05). No animal was successfully resuscitated after a 40-sec delay
      (p < .01). With increasing delays, 24- and 48-hr survival rates were
      correspondingly reduced. CONCLUSIONS: During resuscitation from ventricular
      fibrillation, prolongation of the interval between discontinuation of precordial
      compression and delivery of the first electric countershock substantially
      compromises the success of cardiac resuscitation. Accordingly, automated
      defibrillators are likely to be maximally effective if they are programmed to
      secure minimal "hands off" delay before delivery of the electric countershock.

PMID- 9187588
TI  - Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28
      days fails to improve tissue oxygenation in rats.
AB  - OBJECTIVE: To determine whether the time that red blood cells are stored in
      citrate phosphate dextrose adenine-1 solution before transfusion alters the
      ability to improve tissue oxygenation. DESIGN: Prospective, randomized,
      controlled study. SETTING: University research institute laboratory. SUBJECTS:
      Male Sprague-Dawley rats (350 to 450 g). INTERVENTIONS: Twenty-four hours after
      randomization to sham laparotomy (n = 21) or cecal ligation and perforation (n =
      16)1 supply-dependency of systemic oxygen uptake (VO2) was induced in rats by
      isovolemic hemodilution. Rats were then re-randomized to receive either rat red
      blood cells stored in citrate phosphate dextrose adenine-1 for 3 days ("fresh" n
      = 17) or rat red blood cells stored in citrate phosphate dextrose adenine-1 for
      28 days ("old" n = 20). MEASUREMENTS AND MAIN RESULTS: Changes in systemic VO2
      were measured for 90 mins to determine the efficiacy of the treatment.
      Statistical analysis included a fully factorial repeated-measures, generalized
      linear model. No significant interaction was found between cecal ligation and
      perforation or sham animals and transfusion with fresh or old red blood cells.
      However, comparing the combined groups of animals receiving either fresh or old
      red blood cells, we found that after the transfusion of old red blood cells,
      systemic VO2 was not significantly improved (after hemodilution 1.68 +/- 0.27
      mL/100 g/min, after transfusion 1.86 +/- 0.17 mL/100 g/min; p > .05). In
      contrast, transfusion with fresh red blood cells acutely increased systemic VO2
      (after hemodilution 1.62 +/- 0.06 mL/100 g/min, after transfusion 2.10 +/- 0.09
      mL/100 g/min; p = .049). CONCLUSION: Storage of rat red blood cells for 28 days
      in citrate phosphate dextrose adenine-1 impaired their ability to improve tissue
      oxygenation when transfused into either control or septic rats placed into supply
      dependency of systemic VO2.

PMID- 9187590
TI  - Evaluating laboratory usage in the intensive care unit: patient and institutional
      characteristics that influence frequency of blood sampling.
AB  - OBJECTIVES: To develop a predictive equation to estimate the frequency of blood
      drawing for intensive care unit (ICU) laboratory tests and to evaluate variations
      in ICU blood sampling practices after adjusting for patient and institutional
      factors. DESIGN: Prospective, inception, cohort study. SETTING: Forty-two ICUs in
      40 hospitals, including 20 teaching and 17 nonteaching ICUs. PATIENTS: A
      consecutive sample of 17,440 ICU admissions, in which 14,043 blood samples were
      drawn for laboratory testing on ICU days 2 to 7. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patient demographic, physiologic, and treatment
      data were obtained on ICU day 1; the type and number of blood samples for
      laboratory testing were recorded on ICU days 1 to 7. In the 42 ICUs, a mean of
      16.2 blood samples were drawn for tests on ICU days 2 to 7, but varied between 23
      samples in the teaching ICUs and 9.9 samples in nonteaching ICUs. Using only ICU
      day 1 patient data, we predicted the subsequent number of samples drawn on ICU
      day 2 (R2 = .26 across individual patients) and on ICU days 2 to 7 (R2 = .26
      across individual patients). The most important determinants of the number of
      blood samples drawn on ICU days 2 to 7 were the ICU day 1 Acute Physiology Score
      and admission diagnosis. After controlling for patient variables, hospital
      teaching status, number of beds, and location in the East and South were
      significantly (p < .05) associated with increased blood sampling on ICU day 2 and
      on ICU days 2 to 7. More frequent use of an arterial cannula and mechanical
      ventilation were also associated with increased blood sampling on subsequent
      days. CONCLUSIONS: The ability to adjust for patient and institutional variables
      and to predict the number of blood samples drawn for laboratory tests can allow
      ICUs to compare their practices with those of other units. When integrated into a
      continuous quality improvement process, this information can be used to identify
      and focus on opportunities for improving blood conservation and reducing
      excessive diagnostic testing.

PMID- 9187591
TI  - Functional magnesium deficiency in critically ill patients identified using a
      magnesium-loading test.
AB  - OBJECTIVE: To determine the feasibility of the magnesium-loading test in the
      critically ill and to validate serum ionized magnesium assay using the magnesium
      loading test as a reference in this same patient population. DESIGN: Double
      blind, randomized, controlled clinical investigation. SETTING: Tertiary level
      intensive care unit. PATIENTS: Forty-four consecutive critically ill patients
      without evidence of renal insufficiency. INTERVENTION: Patients were randomly
      allocated to receive 30 mmol (7.5 g) of magnesium sulfate daily for 3 days, or an
      equivalent amount of normal saline. MEASUREMENTS AND MAIN RESULTS: We recorded
      baseline characteristics, and serial serum biochemical measurements included
      creatinine, glucose, sodium, potassium, phosphate, total calcium, ionized
      calcium, total magnesium, and ionized magnesium. Serum assays were accompanied by
      24-hr urine collections of creatinine and magnesium over the 3-day period.
      Baseline characteristics were comparable in both groups. In patients receiving
      magnesium, serum ionized magnesium and total magnesium concentrations were
      increased by 43% (p = .0001) and 59% (p = .0002), respectively, on day 1 as
      compared with the control group. Magnesium excretion in the control group
      averaged 4.8 +/- 2.3 mmol/day during the 3-day study period, while the magnesium
      excretion in the magnesium-loaded group was significantly increased to 22.7 +/-
      10.9 mmol/day (p < .0001). Following day 1 magnesium loading, patients who
      excreted < 70% of the total magnesium (30 mmol infused magnesium plus 4.8 mmol
      basal excretion) were termed as functionally magnesium-deficient retainers (n =
      12), and patients who excreted > 70% of the total magnesium were termed as
      nonretainers (n = 7). In addition, magnesium retainers on day 2 (nine of ten
      patients) and day 3 (five of six patients) excreted > 70% of the total magnesium,
      indicating a replenishment of body magnesium stores. In contrast, nonretainers on
      day 2 (four of five patients), and day 3 (four of four patients) continued to
      excrete excess amounts of magnesium. In the retainer group, only two patients had
      a low serum ionized magnesium concentration, while two other patients had low
      total serum magnesium values. In addition, magnesium retention was associated
      with low ionized calcium and high phosphate values. CONCLUSIONS: The magnesium
      loading test is feasible and appears to be valid based on its performance during
      the 3-day evaluation. Using the magnesium-loading test as a reference, serum
      ionized magnesium appears to be an insensitive biochemical marker of functional
      hypomagnesemia. Larger cohort studies using the magnesium-loading test will help
      establish the true prevalence of magnesium deficiency and its associated risk
      factors in critically ill patients.

PMID- 9187592
TI  - Comparison of pressure- and flow-triggered pressure-support ventilation on
      weaning parameters in patients recovering from acute respiratory failure.
AB  - OBJECTIVE: To compare the effects of pressure- and flow-triggered pressure
      support ventilation on weaning parameters during recovery from acute respiratory
      failure. DESIGN: Prospective, randomized, clinical trial. SETTING: Intensive care
      unit in a university hospital. PATIENTS: Sixteen orotracheally intubated adult
      patients recovering from acute respiratory failure of various etiologies, without
      chronic obstructive pulmonary disease. INTERVENTIONS: Randomized application of
      pressure- and flow-triggered pressure-support ventilation at 100% and 75%
      ventilatory support levels in each triggering system. A total of four conditions
      were applied for 30 mins each in all patients. MEASUREMENTS AND MAIN RESULTS:
      Ventilatory, respiratory, and hemodynamic data were measured. For the measurement
      of weaning parameters, pressure and volume signals were directed to a
      computerized respiratory monitor by means of an esophageal probe and a flow
      sensor between the "Y" piece of the ventilatory circuit and the endotracheal
      tube. During both pressure-triggered (trigger sensitivity of -1 cm H2O) and flow
      triggered (trigger sensitivity of 0.7 to 2.0 L/min) pressure-support ventilation
      with a ventilator, peak airway pressures were applied so as to decrease the work
      of breathing performed by the patient to zero (full ventilatory support). Partial
      ventilatory support was applied at 75% of the peak airway pressures achieved
      during full ventilatory support with each triggering system. A total of four
      experimental conditions were evaluated at identical FiO2 and positive and
      expiratory pressure levels during pressure-support ventilation in each patient.
      Total ventilation volumes, arterial blood gas data, and hemodynamics did not
      differ among the four experimental conditions. During partial ventilatory
      support, the work of breathing, rapid shallow breathing index, and esophageal
      pressure increased significantly with both triggering systems when compared with
      data obtained at full ventilatory support. The mean data for the weaning
      parameters during the condition of partial ventilatory support were comparable
      between pressure- and flow-triggered pressure-support ventilation (i.e., 0.38 +/-
      0.24 vs. 0.42 +/- 0.26 joule/L for work of breathing, 2.6 +/- 1.6 vs. 3.3 +/- 1.7
      cm H2O for tracheal occlusion pressure, and 40.2 +/- 12.9 vs. 50.4 +/- 18.3
      breaths/min/L for rapid shallow breathing index, respectively). CONCLUSIONS: The
      application of either a pressure- or flow-triggered system during pressure
      support ventilation with the ventilator did not significantly affect short-term
      changes in gas exchange, respiratory mechanics, and inspiratory workload in
      patients recovering from acute respiratory failure of various etiologies without
      chronic obstructive pulmonary disease.

PMID- 9187593
TI  - Management of paroxysmal atrioventricular nodal reentrant tachycardia in the
      critically ill surgical patient.
AB  - OBJECTIVES: Paroxysmal atrioventricular nodal reentrant tachycardia is an
      infrequently encountered supraventricular arrhythmia that continues to present
      difficult management problems in the critically ill surgical patient. The purpose
      of this study was to evaluate the efficacy of a new treatment algorithm involving
      the sequential administration of different classes of antiarrhythmic agents until
      conversion to sinus rhythm was achieved. DESIGN: Nonrandomized, consecutive,
      protocol-driven descriptive cohort. SETTING: University hospital surgical and
      trauma intensive care unit (ICU). PATIENTS: During an 11-month period, we
      prospectively evaluated all hemodynamically stable patients who sustained new
      onset atrioventricular nodal reentrant tachycardia. INTERVENTIONS: Vagal
      maneuver, followed by the rapid, sequential infusion of antiarrhythmic agents
      (i.e., adenosine, verapamil, and esmolol, respectively) until the arrhythmia was
      terminated. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (4% of all
      admissions) were evaluated, including 16 trauma patients (injury Severity Score
      of 20 +/- 8) and 11 general surgical patients (Acute Physiology and Chronic
      Health Evaluation II score of 17 +/- 7). Time from ICU admission to onset of
      atrioventricular nodal reentrant tachycardia was 4.5 +/- 5 days (median 2.5).
      Arrhythmia termination was achieved in all patients within minutes (mean 13 +/-
      10 [SD]). Incremental sequential adenosine administration alone, however, was
      successful in affecting conversion to sinus rhythm in only 44% of initial
      episodes of atrioventricular nodal reentrant tachycardia (95% confidence interval
      21% to 67%). A total of 14 (52%) patients developed 38 relapses of paroxysmal
      supraventricular tachycardia in the ICU after initial conversion to sinus rhythm.
      These relapses required additional antiarrhythmic therapy. Adenosine was only
      effective in 34% of the relapses (95% confidence interval 17% to 53%). Seven
      (50%) of these 14 patients developed multiple relapses. However, only two
      patients were receiving suppressive calcium-channel or beta-adrenergic receptor
      blockade at the time of relapse. CONCLUSIONS: The use of a multiagent algorithm
      was effective for the initial conversion of new-onset atrioventricular nodal
      reentrant tachycardia to sinus rhythm in critically ill surgical and trauma
      patients. This preliminary report suggests that adenosine has marginal efficacy
      in the critically ill surgical or trauma patient. Given the high frequency of
      relapses, regardless of the agents used to achieve initial control, suppression
      therapy for the arrhythmia during the period of maximal cardiovascular stress is
      essential.

PMID- 9187594
TI  - Positive end-expiratory pressure increases pulmonary venous vascular resistance
      in patients after coronary artery surgery.
AB  - OBJECTIVE: To investigate the effect of positive and-expiratory pressure (PEEP)
      on the longitudinal distribution of pulmonary vascular resistance in patients
      immediately after coronary artery bypass grafting. DESIGN: Prospective,
      intervention study. SETTING: Postcardiac surgery intensive care unit in a
      teaching institution. PATIENTS: Twenty patients after elective coronary artery
      bypass grafting. INTERVENTION: The effect of PEEP on pulmonary circulation, at
      four different levels (0, 5, 10, and 15 cm H2O), was analyzed in 20 patients.
      MEASUREMENTS AND MAIN RESULTS: Mean pulmonary arterial pressure, left atrial
      pressure, pulmonary artery occlusion pressure, and pulmonary capillary pressure
      were measured at each PEEP level. A model consisting of two resistances in series
      was used to analyze the effect of PEEP on the pulmonary circulation. The
      pulmonary vascular resistance for each area (arterial and venous) of the
      circulation was calculated. Pulmonary vascular resistance increased from 216 +/-
      70 dyne.sec/cm5 at a PEEP of 0 cm H2O to 308 +/- 125 dyne.sec/cm5 at a PEEP of 15
      cm H2O (p < .001). This increase, however, resulted solely from an increase in
      the resistance of the venous part of the pulmonary circulation from 66 +/- 29 to
      134 +/- 69 dyne.sec/cm5 (p < .001), without any change in pulmonary arterial
      resistance. CONCLUSIONS: PEEP increases pulmonary vascular resistance solely by
      increasing pulmonary venous resistance. When applying PEEP, changes in pulmonary
      vascular resistance may impede the resorption of pulmonary edema fluid.

PMID- 9187595
TI  - Assessing the impact of patient characteristics and process performance on rural
      intensive care unit hospital mortality rates.
AB  - OBJECTIVE: To examine the relationship between patient characteristics, processes
      of care, and risk of hospital mortality in rural intensive care units (ICU).
      DESIGN: Retrospective data analysis of ICU patients admitted to 19 rural Iowa
      hospitals between 1992 and 1994. SETTING: ICUs in rural Iowa hospitals. PATIENTS:
      ICU patients treated on mechanical ventilators meeting eligibility criteria.
      MEASUREMENTS AND MAIN RESULTS: Patient age (odds ratio = 1.03, p < .01), a higher
      Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.06, p <
      .01), and a longer pre-ICU length of stay (odds ratio = 1.14, p < .05) were
      associated with a higher risk of death. Seven processes of care were examined
      (i.e., laboratory work, nursing assessment, stress ulcer protection,
      immobilization protection, nutritional management, ventilator management, and
      weaning). Considerable variation was observed between hospitals in performance of
      processes of care. Controlling for patient characteristics, better performance in
      ulcer protection (odds ratio = 0.1, p < .05) and ventilator management (odds
      ratio = 0.03, p < .05) were related to lower risk of mortality. A model
      incorporating both patient characteristics and processes of care achieved higher
      predictive accuracy than a model containing only patient characteristics (area
      under the receiver operating characteristic curve: 0.80 vs. 0.70, p < .01).
      CONCLUSIONS: Most of the variation in mortality was explained by differences in
      patient physiologic and demographic characteristics at ICU admission. After
      adjusting for patient characteristics, better performance in some processes of
      care would have significant impact on reducing risk of mortality.

PMID- 9187596
TI  - Whole-body impedance cardiography in the measurement of cardiac output.
AB  - OBJECTIVE: To evaluate the reliability of whole-body impedance cardiography with
      electrodes on wrists and ankles in the measurement of cardiac output compared
      with the thermodilution method. DESIGN: Prospective, clinical investigation.
      SETTING: Surgical intensive care unit and operating room at a university
      hospital. PATIENTS: Simultaneous cardiac output measurements by thermodilution
      and whole-body impedance cardiography were performed in 74 patients undergoing a
      coronary artery bypass grafting operation. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: A total of 97 triplicate, simultaneous cardiac output measurements
      were carried out with thermodilution and whole-body impedance cardiography: 74
      measurements were conducted in patients who were awake and 23 measurements were
      conducted during anesthesia but before the commencement of surgery. The mean
      cardiac output difference (bias) between the two methods was 0.25 +/- 0.81 (SD)
      L/min; the limits of agreement (2 SD) were-1.37 and 1.87 L/min, respectively. The
      repeatability value (rv = 2.83 x SD) for whole-body impedance cardiography (rv =
      0.46 L/min) was considerably better than for the thermodilution method (rv = 1.05
      L/min). Whole-body impedance cardiography reliably detected cardiac output
      changes induced by head-up tilt before anesthesia, by anesthesia induction, and
      by intubation. Two factors predicted the between-methods stroke volume
      difference: hematocrit (correlation coefficient r = -.36, r2 = .13; p < .001);
      and body mass index (r = .29, r2 = .08; p < .01). Using the multiple linear
      regression equation for correcting the stroke volume by hematocrit and body mass
      index, the limits of agreement (2 SD) between the methods studied were reduced to
      +/-1.28 L/min for cardiac output and +/-0.72 L/min/m2 for cardiac index.
      CONCLUSIONS: There was close agreement between whole-body impedance cardiography
      and thermodilution in the measurement of cardiac output in patients with coronary
      artery disease without cardiac shunts and valvular lesions. The repeatability of
      the impedance method was significantly better than the repeatability of
      thermodilution. Whole-body impedance cardiography can be recommended for the
      assessment of cardiac output and its changes in the resting state. Whole-body
      impedance cardiography is a feasible and handy method for noninvasive and
      continuous measurement of cardiac output.

PMID- 9187597
TI  - Additive beneficial effects of the prone position, nitric oxide, and almitrine
      bismesylate on gas exchange and oxygen transport in acute respiratory distress
      syndrome.
AB  - OBJECTIVE: To test the hypothesis that prone position ventilation, nitric oxide,
      and almitrine bismesylate, each acting by a different mechanism to improve
      arterial oxygenation, could exert additive beneficial effects when used in
      combination in patients with severe acute respiratory distress syndrome (ARDS).
      DESIGN: Prospective, nonrandomized, interventional study. SETTING: Medical and
      surgical intensive care units at a university tertiary care center. PATIENTS:
      Twelve patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of < or =
      150 and FIO2 of > or = 0.6, with pulmonary artery occlusion pressure of < 18 mm
      Hg. INTERVENTIONS: Inhaled nitric oxide (20 parts per million for 15 mins) in the
      supine and prone position, and intravenous almitrine bismesylate while prone (1
      mg/kg/hr for 60 mins), alone or combined with nitric oxide. MEASUREMENTS AND MAIN
      RESULTS: Hemodynamic, blood gas, and gas exchange measurements were performed at
      sequential time points as follows: a) baseline supine; b) nitric oxide in the
      supine position; c) after return to baseline supine; d) after 30 mins prone; e)
      after 120 mins prone; f) nitric oxide while prone; g) after return to baseline
      prone; h) almitrine bismesylate prone; and i) nitric oxide and almitrine
      bismesylate combined, for 15 mins prone. Patients were considered responders to
      the prone position if a gain in PaO2 of > or = 10 torr (> or = 1.3 kPa) or a gain
      in the PaO2/FIO2 ratio of > or = 20 was observed. Seven patients (58%) responded
      to being turned prone. Compared with supine baseline conditions, nitric oxide and
      supine position increased arterial oxygen saturation from 89 +/- 1 (SD)% to 92 +/
      3% (p < .05) and nitric oxide plus prone position increased arterial oxygen
      saturation (94 +/- 3% vs. 89 +/- 4%, p < .05) and decreased the alveolar-arterial
      oxygen difference from 406 +/- 124 torr (54 +/- 15 kPa) to 387 +/- 108 torr (51
      +/- 14 kPa) (p < .05). Almitrine bismesylate increased PaO2/FIO2 vs. baseline
      (122 +/- 58 vs. 84 +/- 21, p < .05). Almitrine bismesylate decreased the alveolar
      arterial oxygen difference vs. baseline from 406 +/- 124 torr (53.9 +/- 16.5 kPa)
      to 386 +/- 112 torr (51.3 +/- 14.8 kPa) and vs. nitric oxide and supine position
      from 406 +/- 111 torr (53.9 +/- 14.7 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa)
      (p < .05). Prone position alone did not improve oxygenation. However, the
      combination of nitric oxide and almitrine bismesylate increased PaO2/FIO2 vs.
      nitric oxide supine and nitric oxide prone conditions (147 +/- 69 vs. 84 +/- 25
      and 91 +/- 18, respectively; p < .05). In patients responding to the prone
      position (n = 7), combining nitric oxide and almitrine bismesylate led to further
      improvement in PaO2 compared with the prone position alone, with PaO2 increasing
      from 78 +/- 12 torr (10.3 +/- 1.6 kPa) to 111 +/- 55 torr (14.7 +/- 7.3 kPa) (p <
      .05), which was not the case when either nitric oxide or almitrine bismesylate
      was added separately. Heart rate and cardiac output were increased by almitrine
      bismesylate compared with all other measurements. Mean pulmonary arterial
      pressure was decreased by nitric oxide (27 +/- 7 vs. 30 +/- 7 mm Hg nitric oxide
      supine vs. baseline supine and 29 +/- 7 vs. 33 +/- 8 mm Hg nitric oxide prone vs.
      baseline prone, p < .05) and increased by almitrine bismesylate (36 +/- 9 vs. 30
      +/- 7 mm Hg baseline supine, 27 +/- 7 mm Hg nitric oxide supine, 33 +/- 8 mm Hg
      baseline prone, and 29 +/- 7 mm Hg nitric oxide prone; p < .05). The increase in
      mean pulmonary arterial pressure was totally abolished by nitric oxide (31 +/- 5
      vs. 36 +/- 9 mm Hg, p < .05). Minute ventilation, respiratory system compliance,
      physiologic deadspace, and PaCO2 remained unchanged. CONCLUSION: In ARDS patients
      with severe hypoxemia, arterial oxygenation can be improved by combining the
      prone position, nitric oxide, and almitrine bismesylate, without deleterious
      effects.

PMID- 9187598
TI  - Effects of pentoxifylline on hemodynamics and oxygenation in septic and nonseptic
      patients.
AB  - OBJECTIVE: To evaluate the effects of pentoxifylline on hemodynamics and systemic
      oxygenation in septic and nonseptic critically ill patients. DESIGN: Prospective
      clinical investigation. SETTING: Intensive care unit (ICU) of a university
      hospital. PATIENTS: Nineteen critically ill patients were included in the study 1
      to 4 days after their admission to the ICU. A systemic inflammatory response
      syndrome was present in 12 patients, fulfilling at least two of the American
      College of Chest Physicians/ Society of Critical Care Medicine Consensus
      Conference criteria. The other seven patients did not fulfill these criteria and
      were classified as nonseptic. INTERVENTIONS: All patients were mechanically
      ventilated. The dosage of catecholamines was kept constant during the entire
      study period and at least during 15 mins before the start of the study. In both
      study groups, pulmonary and radial artery catheters were inserted and 5 mg/kg of
      pentoxifylline (diluted in 300 mL of physiologic saline) was intravenously
      administered over a period of 180 mins at a rate of 100 mL/hr. MEASUREMENTS AND
      MAIN RESULTS: Hemodynamic variables, oxygen transport (DO2), oxygen uptake (VO2),
      and oxygen extraction ratio were determined before pentoxifylline, after 2.5
      mg/kg of pentoxifylline, after 5 mg/kg of pentoxifylline, and 60 mins after the
      termination of pentoxifylline. Repeated-measures analysis of variance and Mann
      Whitney test were used for statistical analysis. At baseline, there were
      significant differences between the septic and the nonseptic groups in mean
      pulmonary arterial pressure (septic: 31 +/- 5 mm Hg; nonseptic: 26 +/- 7 mm Hg, p
      < .05), and pulmonary vascular resistance index (PVRI) (septic: 344 +/- 121
      dyne.sec/ cm5.m2; nonseptic: 233 +/- 100 dyne.sec/cm5.m2, p < .05). In the septic
      group, significant increases in heart rate and cardiac index were observed.
      Systemic vascular resistance index and PVRI decreased. No significant changes in
      hemodynamic variables occurred in the nonseptic group. In both groups, DO2 and
      VO2 increased significantly, while oxygen extraction ratio remained unchanged.
      CONCLUSIONS: The administration of pentoxifylline to septic patients results in a
      significant improvement in hemodynamic performance compared with critically ill
      nonseptic patients. The better hemodynamic state is accompanied by an increase in
      DO2 and VO2 with unchanged oxygen extraction ratio.

PMID- 9187599
TI  - Routine portable chest radiographs in the medical intensive care unit: effects
      and costs.
AB  - OBJECTIVE: To determine the effects and net costs of routine chest radiographs in
      a medical intensive care unit (ICU). DESIGN: A prospective, cohort study. A
      survey of experts in critical care and pulmonary diseases was undertaken to
      assess the effect of routine radiographs on patient management. SETTING: Medical
      ICU of a university hospital. PATIENTS: Eighty randomly selected patients
      admitted to a medical ICU. Two hundred fourteen experts were surveyed; 118
      (55%)/214 responded. MEASUREMENTS AND MAIN RESULTS: Daily interviews with medical
      ICU clinicians were conducted to assess the radiographic findings in the routine
      radiographs and actions taken based on these findings. Experts evaluated the
      findings, their importance, the actions taken, and the probability of
      complications if the actions had not been taken at that time. Experts also
      predicted increases in length of stay associated with these complications.
      Presence of radiographic findings, changes in management because of the findings,
      net costs of routine chest radiographs, cost per finding that prompted an action,
      and expected changes in length of stay resulting from the actions were also
      assessed. Seventy-two (33%) of 221 routine radiographs (95% confidence interval:
      25% to 39%) had findings, of which 44 (61%) were judged important, and 18 (8%,
      95% confidence interval: 5% to 12%) prompted actions. Experts predicted that each
      action averted, on average, 2.1 +/- 1.7 days (SD) in the medical ICU. Mean
      savings per routine radiograph was $98. Net savings from routine chest
      radiographs remained after sensitivity analysis for expected change in length of
      stay, percentage of patients with routine radiographs, and percentage of routine
      radiographs that produce changes in management. CONCLUSION: The policy of
      obtaining routine chest radiographs in the medical ICU is effective and results
      in net savings.

PMID- 9187600
TI  - Relationship between hemodynamic and vital support measures and pharmacokinetic
      variability of amikacin in critically ill patients with sepsis.
AB  - OBJECTIVE: To examine the relationship between aminoglycoside disposition
      kinetics and hemodynamic response to sepsis, as well as vital support therapy, in
      critically ill patients with sepsis. DESIGN: Cross-sectional study of critically
      ill patients with sepsis undergoing physiologic and aminoglycoside
      pharmacokinetic monitoring. SETTING: Ten-bed general intensive care unit in a
      tertiary care center. PATIENTS: Thirty consecutive critically ill patients who
      had Gram-negative sepsis treated with amikacin and who were undergoing
      hemodynamic monitoring. INTERVENTIONS: Clinical, hemodynamic, oxygenation, and
      amikacin pharmacokinetic data were obtained simultaneously in each patient during
      aminoglycoside therapy. MEASUREMENTS AND MAIN RESULTS: Aminoglycoside
      pharmacokinetic values were estimated from serum amikacin concentration-time data
      using a nonlinear least squares regression computer program, assuming a one
      compartment infusion pharmacokinetic model. Individual pharmacokinetic values
      were subjected to statistical analysis to explain their variability. Selection of
      the subset of variables to be used in the final model was performed by combining
      principal component analysis and multiple stepwise linear regression. The mean
      prediction error and the root mean square error, as expressions of bias and
      precision, were estimated. Mean volume of distribution was 0.47 L/kg, with a
      coefficient of variation of 35%. Mean serum amikacin clearance was 60.2 mL/min,
      with a coefficient of variation of 34%. Seventy-six percent of the variability in
      volume of distribution was explained by three covariates: body weight (p <
      .0001); oxygen extraction (p < .001); and serum albumin (p < .001). For serum
      amikacin clearance, 70% of the variability was explained by three covariates:
      creatinine clearance (p < .001); positive end-expiratory pressure (p < .01); and
      use of catecholamines as vital support therapy (p < .05). CONCLUSIONS: Factors
      related to hemodynamic response and vital support measures have a significant
      influence on the disposition kinetics of amikacin in severely ill patients with
      sepsis. Consideration of hemodynamic response and vital support measures, in
      addition to other previously described covariates, can be of great value in the
      design of initial dosing regimens.

PMID- 9187601
TI  - Extensive tyrosine nitration in human myocardial inflammation: evidence for the
      presence of peroxynitrite.
AB  - OBJECTIVES: Production of nitric oxide via the cytokine-mediated activation of
      myocardial inducible nitric oxide synthase decreases myocardial contractility.
      Whether myocardial dysfunction is mediated directly by nitric oxide or indirectly
      through the formation of secondary reaction products, such as peroxynitrite, has
      not been established. Peroxynitrite, but not nitric oxide, reacts with the
      phenolic ring of tyrosine to form the stable product 3-nitro-L-tyrosine.
      Demonstration of tissue nitrotyrosine residues, therefore, infers the presence of
      peroxynitrite or related nitrogen-centered oxidants. DESIGN: Retrospective
      analysis of human autopsy specimens. SETTING: University pathology and basic
      science laboratories. PATIENTS: Formalin-fixed, paraffin-embedded myocardial
      tissue samples were obtained from 11 patients with a diagnosis of sepsis, seven
      patients with a diagnosis of viral myocarditis, and five control patients without
      clinical or pathologic cardiac disease. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Specific antibodies to nitrotyrosine were utilized to detect
      nitrotyrosine residues in human autopsy specimens. Cardiac tissue obtained from
      patients with myocarditis or sepsis demonstrated intense nitrotyrosine
      immunoreactivity in the endocardium, myocardium, and coronary vascular
      endothelium and smooth muscle. In contrast, connective tissue elements were
      without appreciable immunohistochemical staining. Nitrotyrosine antibody binding
      was blocked by coincubation with nitrotyrosine or nitrated bovine serum albumin,
      but not by aminotyrosine, phosphotyrosine, or bovine serum albumin. In situ
      reduction of tissue nitrotyrosine to aminotyrosine by sodium hydrosulfite also
      blocked antibody binding. Densitometric analysis of nitrotyrosine
      immunoreactivity demonstrated significantly higher values for specimens from
      myocarditis and sepsis patients when compared with control tissue specimens.
      CONCLUSION: These results demonstrate the formation of peroxynitrite within the
      myocardium during inflammatory disease states, suggesting a role for
      peroxynitrite in inflammation-associated myocardial dysfunction.

PMID- 9187602
TI  - The atrial natriuretic peptide receptor antagonist HS 142-1 improves
      cardiovascular filling and mean arterial pressure in a hyperdynamic ovine model
      of sepsis.
AB  - OBJECTIVE: To test whether systemic vascular resistance and mean arterial
      pressure increase during the administration of the atrial natriuretic peptide
      antagonist, HS 142-1, in ovine experimental hyperdynamic sepsis. DESIGN:
      Prospective trial. SETTING: Research laboratory at a large university medical
      center. SUBJECTS: Chronically instrumented Merino breed ewes (n = 14).
      INTERVENTIONS: Continuous infusion of Pseudomonas aeruginosa (2.5 x 10(6) colony
      forming units/min) for the experimental period of 48 hrs. One group (HS 142-1)
      received a continuous infusion of HS 142-1 (3 mg/kg/hr) from 40 to 48 hrs; the
      remaining sheep ("control") were given the vehicle sodium chloride 0.9%.
      MEASUREMENTS AND MAIN RESULTS: All sheep developed a hyperdynamic cardiovascular
      response by 40 hrs that was characterized by low values of systemic vascular
      resistance index (p < .05) and mean arterial pressure (p < .05), and an increased
      cardiac index (p < .05). HS 142-1 increased cardiac filling pressures (p < .05)
      without apparent effects on fluid balance, and was associated with a
      significantly (p < .05) higher mean arterial pressure than was found in the
      control group at 44 and 48 hrs. HS 142-1 did not change systemic vascular
      resistance index. At 44 and 48 hrs, cardiac index values were found to have
      significantly (p < .05) increased in the animals receiving HS 142-1, when these
      data were compared with cardiac output values at 40 hrs. CONCLUSION: HS 142-1
      increases cardiac filling pressures and maintains mean arterial pressure in
      hyperdynamic sepsis without reversal of sepsis-induced vasodilation.

PMID- 9187603
TI  - Induction of endotoxin tolerance in rat bone marrow cells by in vivo infusion of
      tumor necrosis factor.
AB  - OBJECTIVE: To determine in a rat model whether a low-dose infusion of tumor
      necrosis factor (TNF) affects the production of the inflammatory cytokines TNF
      and interleukin (IL)-6, the immunosuppressive factor prostaglandin E2 (PGE2), and
      complement component C3 (C3) by isolated bone marrow-adherent and -nonadherent
      cells, cultured in the presence of lipopolysaccharide, a component of bacterial
      endotoxin. DESIGN: Randomized, controlled animal study. SETTING: Research
      laboratory of a university medical center. SUBJECTS: Sprague-Dawley rats (n =
      18), 250 to 275 g. INTERVENTIONS: Animals received a continuous infusion of one
      of the following three treatments for 4 days: a) TNF in saline containing bovine
      serum albumin; b) saline containing bovine serum albumin; and c) saline alone.
      MEASUREMENTS AND MAIN RESULTS: After infusion, isolated bone marrow cells were
      cultured for 1 day and 3 days, with and without lipopolysaccharide (1
      microgram/mL); culture supernatants were assayed for TNF, IL-6, PGE2, and C3. TNF
      infusion caused a decrease in the in vitro production of TNF, IL-6, and PGE2 by
      the lipopolysaccharide-stimulated adherent and nonadherent bone marrow cells.
      This tolerance to lipopolysaccharide stimulation was present after both 1 day and
      3 days of culture. TNF infusion caused an increase in C3 production by the
      nonadherent cells. The production of TNF by adherent cells from saline-infused or
      bovine serum albumin-infused animals (controls) was greater in 3-day cultures
      compared with 1-day cultures, whereas the production of IL-6 and PGE2 was less.
      CONCLUSIONS: These results indicate that TNF infusion caused cells in the bone
      marrow to be tolerant to lipopolysaccharide stimulation or that TNF infusion
      programmed the cells to become tolerant to lipopolysaccharide stimulation on
      differentiation and/or maturation. The results also indicate that bone marrow
      cells may be regulated by TNF (probably indirectly) at different phases of
      maturation and/or differentiation with respect to the production of different
      mediators. Although TNF is considered to be an inflammatory cytokine, at low
      concentrations it may be an important down-regulator of the inflammatory
      response.

PMID- 9187604
TI  - Scorpion venom leads to gastrointestinal ischemia despite increased oxygen
      delivery in pigs.
AB  - OBJECTIVES: Scorpion envenomation may be accompanied by metabolic acidosis even
      in the absence of hypoxia and cardiovascular derangement. We tested the
      hypothesis that venom causes ischemia of the gastrointestinal tract rather than
      failure of delivery of oxygen to the periphery. DESIGN: Repeated measures,
      prospective study in experimental animals. SETTING: University-affiliated
      hospital research laboratory. INTERVENTIONS: In ten spontaneously breathing,
      intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05
      mg/kg, was administered intravenously. Measurements were obtained before
      (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection.
      MEASUREMENTS AND MAIN RESULTS: Variables measured included: mean arterial
      pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary
      artery occlusion pressure, cardiac output, stroke volume, right ventricular
      ejection fraction (rapid thermistor), left ventricular dimensions
      (echocardiography), arterial gas tensions, lactate and catecholamine
      concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic
      and pulmonary vascular resistances. Within 5 mins after venom injection, there
      was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to
      136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006),
      and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no
      change in stroke volume, or pulmonary artery occlusion pressure. Right
      ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p <
      .0009) by 15 mins. No change in left ventricular function was observed. There
      were significant decreases in systemic vascular resistance and pulmonary vascular
      resistance following envenomation. Arterial and gastric mucosal pH significantly
      decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and
      7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins
      after envenomation. The decrease in arterial pH was not sufficient to account for
      the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial
      lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were
      significant increases in serum epinephrine and norepinephrine values by 5 mins.
      All hemodynamic variables and catecholamine concentrations returned to baseline
      by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and
      increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal
      or supernormal for 4 hrs following envenomation. However, despite this finding,
      systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen
      delivery. CONCLUSIONS: Despite increased peripheral oxygen delivery, scorpion
      envenomation was associated with evidence of ischemia of the gastrointestinal
      tract. This association could be due to shunting of blood from metabolically
      active areas, possibly associated with massive catecholamine release, or a direct
      toxic effect of the venom on regional oxygen transport at the cellular level.

PMID- 9187605
TI  - Extracellular acidosis delays cell death against glucose-oxygen deprivation in
      neuroblastoma x glioma hybrid cells.
AB  - OBJECTIVE: To determine whether extracellular acidosis delays cell death against
      glucose-oxygen deprivation and, if so, whether this result is due to inhibition
      of calcium (Ca2+) influx or preservation of cellular energy state. DESIGN:
      Randomized, controlled, prospective study. SETTING: University research
      laboratory. SUBJECTS: Differentiated neuroblastoma x glioma NG108-15 cells.
      INTERVENTIONS: Experiment 1: cells were incubated for 8 hrs in N-(2
      hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-buffered medium under glucose
      oxygen deprivation at pH 7.4, 6.8, 6.5, 6.2, 5.6, or 5.0. Experiment 2: cells
      were incubated for 8 hrs under glucose-oxygen deprivation after excluding
      extracellular calcium from culture medium at pH 7.4 or 6.2. Experiment 3: cells
      were incubated for 2, 4, 6, or 8 hrs in N-(2-hydroxyethyl)piperazine-N'-2
      ethanesulfonic acid-buffered medium under glucose-oxygen deprivation at pH 7.4 or
      6.2 and assayed for high-energy phosphates. MEASUREMENTS AND MAIN RESULTS: Cell
      viability was measured with flow cytometry after the cells were stained with
      fluorescein diacetate and propidium iodide. Cellular adenosine triphosphate,
      adenosine diphosphate, and adenosine monophosphate were analyzed with high
      performance liquid chromatography. Cell viability was significantly greater at pH
      6.2 than at pH 7.4 in experiment 1. By excluding extracellular calcium, a
      significant difference in viability between pH 7.4 and 6.2 persisted in
      experiment 2. Energy charge and the concentration of adenosine triphosphate were
      significantly greater at pH 6.2 than at pH 7.4 in the intervals preceding
      manifestation of a differential effect of acidosis on cell viability in
      experiment 3. CONCLUSIONS: Extracellular acidosis at pH 6.2 delayed cell death
      against glucose-oxygen deprivation. This protective effect by extracellular
      acidosis may be due to preservation of the cellular energy state in NG108-15
      cells, although this study does not exclude the possibility that in other cell
      types, inhibition of calcium influx may have an effect.

PMID- 9187606
TI  - The endothelin receptor antagonist, bosentan, in combination with the
      cyclooxygenase inhibitor, diclofenac, counteracts pulmonary hypertension in
      porcine endotoxin shock.
AB  - OBJECTIVE: To prevent endotoxin-induced pulmonary hypertension in the pig with a
      combination of a nonpeptide mixed endothelin receptor antagonist, bosentan, and a
      cyclooxygenase inhibitor, diclofenac. DESIGN: Prospective, controlled trial.
      SETTING: Animal laboratory at a large university medical center. SUBJECTS: Twelve
      domestic pigs, weighing 17.5 to 27 kg. INTERVENTIONS: Endotoxin shock was induced
      by intravenous infusion of Escherichia coli lipopolysaccharide endotoxin (15
      micrograms/kg/hr). Six pigs receiving only endotoxin served as controls. Six pigs
      were pretreated with intravenous bolus injections of bosentan (5 mg/kg) and
      diclofenac (3 mg/kg) followed by a continuous bosentan infusion (2.5 mg/kg/hr).
      MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics and regional circulation
      were measured using ultrasonic flow probes. Arterial and mixed venous blood
      samples were collected regularty for determination of Big endothelin-1-like
      immunoreactivity, endothelin-1-like immunoreactivity, norepinephrine, and blood
      gases. The bosentan/diclofenac pretreatment per se significantly decreased mean
      pulmonary arterial pressure (p < .001), pulmonary vascular resistance index (p <
      .001), and mean arterial blood pressure (p < .001), but cardiac index did not
      change. Splenic blood flow increased (p < .01) while renal blood flow decreased
      (p < .001). In addition, intestinal blood flow decreased slightly (p < .05). In
      the control group, only three animals survived the 3 hrs of endotoxin infusion,
      while all pretreated animals survived. The biphasic increase in mean pulmonary
      arterial pressure and pulmonary vascular resistance index seen in control animals
      during endotoxemia was markedly attenuated in animals pretreated with the
      bosentan/diclofenac combination. The pretreated group generally showed a
      favorable hemodynamic course, with a relatively higher cardiac index, stroke
      volume index, and splenic and renal blood flow. In control animals, a pronounced
      metabolic acidosis developed during endotoxin infusion. A relatively higher
      arterial plasma concentration of endothelin-1-like immunoreactivity was reached
      in pretreated animals, while the Big endothelin-1-like immunoreactivity plasma
      increase was similar in both groups. Arterial concentrations of norepinephrine
      were significantly (p < .01) higher in control animals when compared with
      diclofenac/bosentan-treated animals. CONCLUSIONS: The combination of bosentan and
      diclofenac induced systemic and pulmonary vasodilation in the intrinsic state.
      During endotoxin shock, this drug combination efficiently counteracts pulmonary
      hypertension and improves cardiac performance and splenic and renal blood flow.
      These favorable circulatory effects may have resulted in a reduction of both
      sympathetic nervous system activation and metabolic acidosis. Thus, we conclude
      that the endothelin receptors participate in intrinsic regulation of vascular
      tone in the anesthetized pig. During endotoxin shock, blockade of these
      receptors, as well as inhibition of the cyclooxygenase enzymes, contributes to a
      less adverse effect on the systemic and pulmonary circulation.

PMID- 9187607
TI  - N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion
      and macromolecular leakage in vivo.
AB  - OBJECTIVE: To determine the influence of N-acetylcysteine on endotoxin-induced
      leukocyte-endothelial cell adhesion, vascular leakage, and venular
      microhemodynamics. DESIGN: Randomized, blinded, controlled trial. SETTING:
      Experimental laboratory. SUBJECTS: Thirty male Wistar rats. INTERVENTIONS: After
      pretreatment with N-acetylcysteine (150 mg/kg; n = 40; group A) or 0.9% saline
      solution (n = 10; group B) animals were given an intravenous infusion of
      endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins.
      Animals in the control group (n = 10; group C) received a volume-equivalent
      infusion of 0.9% saline solution. MEASUREMENTS AND MAIN RESULTS: Leukocyte
      adherence, red cell velocity (VRBC), vessel diameters, venular wall shear rate,
      and macromolecular leakage were determined in mesenteric postcapillary venules
      using in vivo videomicroscopy at baseline and at 30, 50, 90, and 120 mins after
      the start of the endotoxin challenge. Endotoxin exposure induced a marked
      increase in adherent leukocytes (group B: baseline, 391 +/- 24 cells/mm2; 120
      mins, 1268 +/- 131 cells/mm2; p < .01). N-acetylcysteine pretreatment attenuated
      the adherence of leukocytes during endotoxemia (baseline, 366 +/- 28 cells/mm2;
      120 mins, 636 +/- 49 cells/mm2; p < .01 vs. baseline; p < .01 vs. group B).
      Leukocyte adherence in control animals (group C) did not increase significantly.
      Administration of N-acetylcysteine did not influence the decrease in VRBC
      observed during endotoxemia. In group B1 VRBC decreased during the infusion of
      endotoxin from 2.0 +/- 0.2 mm/sec at baseline to 1.1 +/- 0.2 mm/ sec after 120
      mins (p < .01 vs. baseline; p < .05 vs. group C), and in group A from 2.2 +/- 0.2
      mm/sec to 1.1 +/- 0.1 mm/sec after 120 mins (p < .01 vs. baseline; p < .05 vs.
      group C). In group C, VRBC remained unchanged (baseline, 1.7 +/- 0.2 mm/sec; at
      120 mins, 1.5 +/- 0.2 mm/sec). The venular diameters remained unchanged in all
      groups during the entire study period. After 120 mins, the venular wall shear
      rate decreased from 502 +/- 62 secs-1 at baseline to 272 +/- 46 sec-1 in group B
      (p < .01), and from 563 +/- 45 secs-1 at baseline to 283 +/- 31 secs-1 in group A
      (p < .01). No differences in venular wall shear rate were observed between these
      groups. In group C, the venular wall shear rate remained unchanged (baseline, 457
      +/- 54 secs-1; at 120 mins, 409 +/- 51 secs-1). Macromolecular leakage, expressed
      as perivenular/intravenular fluorescence intensity after injection of
      fluorescence-labeled albumin, increased from 0.29 +/- 0.03 to 0.58 +/- 0.03 (p <
      .01) during the infusion of endotoxin in group B. In contrast, pretreatment with
      N-acetylcysteine diminished the extravasation of albumin (baseline, 0.27 +/-
      0.01; at 120 mins, 0.37 +/- 0.02; p < .01 vs. baseline; p < .01 vs. group B).
      CONCLUSION: These results demonstrate that N-acetylcysteine attenuates endotoxin
      induced alterations in leukocyte-endothelial cell adhesion and macromolecular
      leakage, suggesting N-acetylcysteine might be therapeutic in the prevention of
      endothelial damage in sepsis.

PMID- 9187608
TI  - Noninvasive determination of cardiac output in a model of acute lung injury.
AB  - OBJECTIVE: To examine the utility of single breath CO2 analysis as a noninvasive
      measure of cardiac output in a model of acute lung injury. SETTING: An animal
      laboratory in a university-affiliated medical center. DESIGN: A prospective,
      animal cohort study comparing 21 parameters derived from single breath CO2
      analysis with cardiac output determined by an ultrasonic flow probe. SUBJECTS:
      Six adult sheep with saline lavage-induced acute lung injury. INTERVENTIONS:
      Animals were treated with repetitive saline lavage to achieve a uniform degree of
      acute lung injury (PaO2 of < 100 torr [< 13.32 kPa] on an FIO2 of 1.0). Cardiac
      output was manipulated by successive injections of an hydraulic constrictor
      placed around the inferior vena cava and measured using an ultrasonic flow probe.
      Twenty-one derived components of the CO2 expirogram were evaluated as predictors
      of cardiac output. MEASUREMENTS AND MAIN RESULTS: Thirty-eight measurements of
      cardiac output were available for comparison with derived variables from the CO2
      expirogam. Stepwise linear regression identified four variables for the equation
      predicting cardiac output: a) PaO2/FIO2 ratio; b) the angle between the slope
      lines for phases II and III divided by the tidal volume; c) mixed expired CO2
      tension; and d) physiologic deadspace to tidal volume ratio. The multivariate
      equation was highly statistically significant and explained 80% of the variance
      (adjusted R2 = .80, p < .0001). The blas and precision of the calculated cardiac
      output were .00 and .38, respectively. The mean percent difference for the
      cardiac output estimates derived from the single breath CO2 analysis station was 
      0.01%. CONCLUSIONS: Our results indicate that changes in cardiac output can be
      determined using components of the CO2 expirogram with a high degree of
      reliability in animals with induced acute lung injury. Specifically, the use of
      four parameters derived from a plot of expired CO2 concentration vs. expired
      volume predict changes in cardiac output in adult sheep with induced lung injury
      with an adjusted coefficient of determination of .80. Prospective application of
      this technology in the clinical setting with the rapidly changing physiology that
      is characteristic of the acutely ill patient will be essential in determining the
      clinical usefulness of single breath CO2 analysis as a noninvasive measure of
      cardiac output.

PMID- 9187609
TI  - Impaired microvascular vasoconstrictive responses to vasopressin in septic rats.
AB  - OBJECTIVE: To evaluate mechanisms of vasodilation in sepsis by comparing
      responses of resistance arterioles to vasopressin in rat cremaster muscle of
      septic and control rats. DESIGN: Prospective, experimental study. SETTING:
      Experimental animal laboratory. SUBJECTS: Twenty male rats, anesthetized with
      ketamine and acepromazine. INTERVENTIONS: Topical superfusion of vasoactive
      compounds on skeletal muscle resistance arterioles. MEASUREMENTS AND MAIN
      RESULTS: The effect of sepsis on responses to local application of vasopressin
      was investigated using in vivo videomicroscopy. Vasopressin was superfused
      topically on the cremaster muscle resistance arterioles (15 to 25 microns) of
      rats made septic by cecal ligation and puncture, and the responses were compared
      with the responses of controls that underwent sham ligation. Responses to
      topically suffused vasopressin were also assessed in septic and control rats,
      before and after superfusion of the muscle with the nitric oxide synthase
      inhibitor NG-methyl-L-arginine (NMA). Sepsis produced a decrease in the
      vasoconstrictive effects of vasopressin; the maximal response was lower, and the
      concentration-response curve was shifted to the right in septic rats (p < .05).
      Contractions at vasopressin concentrations of 0.01, 1, and 10 nM were 39%, 36%,
      and 40%, respectively, of sham controls. Superfusion of the muscle with NMA
      partially restored arteriolar responsiveness in the septic rats, significantly
      increasing the arteriolar constriction of the septic rats in response to
      vasopressin. This effect was reversed with superfusion of excess L-arginine (1
      mM). CONCLUSIONS: This study illustrates the reduced responsiveness of the
      resistance arterioles of septic rats in response to vasopressin in vivo, and the
      partial restoration of responsiveness by concurrent application of NMA. In
      previous studies using this model, we have shown similar results using
      norepinephrine and endothelin-1, as well as angiotensin II. These findings, and
      the findings of this study, suggest a generalized abnormality in responsiveness
      of resistance arterioles to endogenous vasoconstrictors in sepsis. Partial
      reversal of this abnormality with NMA supports an important role for nitric oxide
      in mediating abnormal vasopressor responsiveness in sepsis.

PMID- 9187610
TI  - Gabexate mesilate, a synthetic protease inhibitor, prevents compression-induced
      spinal cord injury by inhibiting activation of leukocytes in rats.
AB  - OBJECTIVE: Gabexate mesilate is a synthetic protease inhibitor capable of
      inhibiting both coagulation and cytokine production by monocytes. To investigate
      whether gabexate mesilate is useful for the prevention of posttraumatic spinal
      cord injury, we examined its effect on compression trauma-induced spinal cord
      injury in rats. DESIGN: Prospective, randomized, blinded, controlled study.
      SETTING: Research laboratory at a university medical center. SUBJECTS: Male
      Wistar rats weighing 300 to 350 g. INTERVENTIONS: Spinal cord injury was induced
      by applying a 20-g weight extradurally to the spinal cord at the level of the
      12th thoracic vertebra for 20 mins. Spinal cord injury was evaluated by assessing
      the motor function of the rats 24 hrs posttrauma. The accumulation of leukocytes
      and histologic changes in the injured spinal cord tissue also were examined. Rats
      received gabexate mesilate (10 or 20 mg/kg i.p.) 30 mins before or after the
      compressive trauma. The effects of heparin or an inactive derivative of activated
      factor X (a selective inhibitor of thrombin generation) on compressive trauma
      induced spinal cord injury also were examined. Leukocytopenia was induced by the
      administration of nitrogen mustard. MEASUREMENTS AND MAIN RESULTS: The motor
      disturbances observed following traumatic spinal cord compression, evaluated by
      Tarlov's score, and the accumulation of leukocytes in the injured tissue,
      evaluated by measuring tissue myeloperoxidase activity, were markedly reduced by
      leukocyte depletion induced by nitrogen mustard and by pre- or posttreatment of
      animals with gabexate mesilate. Neither heparin nor the inactive derivative of
      activated factor X prevented the motor disturbances and the accumulation of
      leukocytes. Histologic examination demonstrated that intramedullary hemorrhages
      observed 24 hrs after trauma at the 12th thoracic vertebra were significantly
      attenuated by nitrogen mustard-induced leukocytopenia and the administration of
      gabexate mesilate. CONCLUSIONS: The compression trauma-induced spinal cord injury
      demonstrated by this model was mainly mediated by leukocytes. Gabexate mesilate
      prevented spinal cord injury not by inhibiting coagulation, but by inhibiting the
      activation of leukocytes.

PMID- 9187612
TI  - Consensus statement of the Society of Critical Care Medicine's Ethics Committee
      regarding futile and other possibly inadvisable treatments.
AB  - OBJECTIVES: Society must always face the reality of limited medical resources and
      must find mechanisms for distributing these resources fairly and efficiently. One
      recent approach for distributing limited medical resources has been the
      development of policies that limit the availability of futile treatments. The
      objectives of this consensus statement are as follows: a) to define futility and
      thereby enable a clear discussion of the issues; and b) to identify principles
      and procedures for resolving cases in which life-sustaining treatment may be
      futile or inadvisable. DATA SOURCES: A literature review, synthesis, and
      committee discussion. CONCLUSIONS: Treatments should be defined as futile only
      when they will not accomplish their intended goal. Treatments that are extremely
      unlikely to be beneficial, are extremely costly, or are of uncertain benefit may
      be considered inappropriate and hence inadvisable, but should not be labeled
      futile. Futile treatments constitute a small fraction of medical care. Thus,
      employing the concept of futile care in decision-making will not primarily
      contribute to a reduction in resource use. Nonetheless, communities have a
      legitimate interest in allocating medical resources by limiting inadvisable
      treatments. Communities should seek to do so using a rationale that is explicit,
      equitable, and democratic; that does not disadvantage the disabled, poor, or
      uninsured; and that recognizes the diversity of individual values and goals.
      Policies to limit inadvisable treatment should have the following
      characteristics: a) be disclosed in the public record; b) reflect moral values
      acceptable to the community; c) not be based exclusively on prognostic scoring
      systems; d) articulate appellate mechanisms; and e) be recognized by the courts.
      Healthcare organizations that control payment have a profound influence on
      treatment decisions and should formally address criteria for determining when
      treatments are inadvisable and should share accountability for those decisions.

PMID- 9187611
TI  - Successful treatment of severe dysrhythmias in infants with respiratory syncytial
      virus infections: two cases and a literature review.
AB  - OBJECTIVES: To describe severe myocardial manifestations in two infants with
      respiratory syncytial virus infection and to review published literature
      reporting cardiac involvement in patients with respiratory syncytial virus
      disease. DESIGN: Case report and literature review. SETTING: Tertiary care
      pediatric intensive care unit (ICU). PATIENTS: Two infants admitted to the
      pediatric ICU for dysrhythmias and severe myocardial dysfunction and infected
      with respiratory syncytial virus. INTERVENTIONS: Conventional cardiovascular,
      antidysrhythmic, and respiratory support, as well as extracorporeal membrane
      oxygenation and high-frequency oscillatory ventilation. MEASUREMENTS AND MAIN
      RESULTS: Both patients had respiratory syncytial virus infections and clinical
      evidence of severe myocarditis, with dysrhythmias, cardiomegaly, and cardiogenic
      shock. Both infants survived their hospitalizations. To our knowledge, these two
      patients are the first reported cases of myocarditis in infants with respiratory
      syncytial virus infection. CONCLUSIONS: Severe myocardial dysfunction and
      dysrhythmias may accompany respiratory syncytial virus infection in some infants
      and may be reversible with aggressive supportive therapy.

PMID- 9187613
TI  - Administration of amphotericin B in lipid emulsion.

PMID- 9187615
TI  - Extracellular water measured by bioimpedance.

PMID- 9187614
TI  - Administration of amphotericin B in lipid emulsion.

PMID- 9187616
TI  - Cerebral perfusion pressure monitoring alert!

PMID- 9187617
TI  - Cows' milk fat components as potential anticarcinogenic agents.
AB  - The optimum approach to conquering cancer is prevention. Although the human diet
      contains components which promote cancer, it also contains components with the
      potential to prevent it. Recent research shows that milk fat contains a number of
      potential anticarcinogenic components including conjugated linoleic acid,
      sphingomyelin, butyric acid and ether lipids. Conjugated linoleic acid inhibited
      proliferation of human malignant melanoma, colorectal, breast and lung cancer
      cell lines. In animals, it reduced the incidence of chemically induced mouse
      epidermal tumors, mouse forestomach neoplasia and aberrant crypt foci in the rat
      colon. In a number of studies, conjugated linoleic acid, at near-physiological
      concentrations, inhibited mammary tumorigenesis independently of the amount and
      type of fat in the diet. In vitro studies showed that the milk phospholipid,
      sphingomyelin, through its biologically active metabolites ceramide and
      sphingosine, participates in three major antiproliferative pathways influencing
      oncogenesis, namely, inhibition of cell growth, and induction of differentiation
      and apoptosis. Mice fed sphingomyelin had fewer colon tumors and aberrant crypt
      foci than control animals. About one third of all milk triacylglycerols contain
      one molecule of butyric acid, a potent inhibitor of proliferation and inducer of
      differentiation and apoptosis in a wide range of neoplastic cell lines. Although
      butyrate produced by colonic fermentation is considered important for colon
      cancer protection, an animal study suggests dietary butyrate may inhibit mammary
      tumorigenesis. The dairy cow also has the ability to extract other potential
      anticarcinogenic agents such as beta-carotene, beta-ionone and gossypol from its
      feed and transfer them to milk. Animal studies comparing the tumorigenic
      potential of milk fat or butter with linoleic acid-rich vegetable oils or
      margarines are reviewed. They clearly show less tumor development with dairy
      products.

PMID- 9187618
TI  - New insights into the utilization of medium-chain triglycerides by the neonate:
      observations from a piglet model.
AB  - Because of their unique digestive and metabolic properties, medium-chain
      triglycerides (MCT) are used in a variety of nutritional settings, including use
      as a readily digestible energy source for the neonate. This review examines
      recent findings from our laboratory related to MCT digestion and metabolism that
      are drawn from a neonatal piglet model, but which may be clinically relevant to
      human infants. We have shown that MCT utilization improves rapidly with postnatal
      age (within 24 h), which is likely due to the ontogeny of pancreatic lipase.
      Additional data delineate the dramatic effects of emulsification and fatty acid
      chain length (within the medium-chain family) on utilization, with the suggestion
      that triacylhexanoate is utilized at the highest rate. Again, these effects are
      likely mediated via an increase in the kinetics of digestion rather than
      metabolism. Indeed, using both in vitro and in vivo radiotracer techniques, we
      were unable to detect metabolic differences among even-chain fatty acid
      homologues. However, studies with isolated hepatocytes have shown greater
      oxidation rates of odd-chain fatty acids compared with even-chain homologues, in
      part as a result of the anaplerotic potential of propionyl-CoA arising from odd
      carbon fatty acid oxidation. In vivo radiotracer studies also showed an
      improvement in octanoate oxidation to CO2, with a concomitant reduction in
      urinary dicarboxylic acid excretion when colostrum-deprived piglets were
      supplemented with L-carnitine. Further metabolic research led to the novel
      finding that piglets have a very limited hepatic capacity to synthesize ketone
      bodies, and that acetate may be a relatively important product of hepatic fatty
      acid oxidation in this species.

PMID- 9187620
TI  - Dietary soybean protein increases insulin receptor gene expression in Wistar
      fatty rats when dietary polyunsaturated fatty acid level is low.
AB  - To investigate the effects of different dietary fatty acids and proteins on
      glucose tolerance and insulin receptor gene expression, Wistar fatty rats
      (genetically obese, noninsulin-dependent diabetes mellitus) and their lean
      littermates (8 wk old) were fed a casein or soybean protein diet containing 9%
      partially saturated beef tallow (plus 1% corn oil), 10% corn oil or 10% fish oil
      for 3 wk. In glucose tolerance tests, plasma insulin concentrations were
      significantly higher in obese rats fed corn oil or fish oil than in those fed
      partially saturated beef tallow, particularly in the soybean protein groups.
      However, plasma glucose concentrations were not significantly affected by dietary
      protein or fat. The insulin receptor mRNA concentrations in livers and adipose
      tissues were higher in rats fed soybean protein/partially saturated beef tallow
      than in those fed any other protein/fat combination. Dietary soybean protein may
      help to reduce the insulin resistance, but only when a diet low in
      polyunsaturated fatty acids is consumed. On the other hand, the insulin receptor
      mRNA concentrations in adipose tissue were generally lower in the obese rats of
      all dietary groups than in the lean rats, suggesting that insulin resistance may
      be due to a defect of insulin receptor gene expression.

PMID- 9187619
TI  - Fecal losses of sterols and bile acids induced by feeding rats guar gum are due
      to greater pool size and liver bile acid secretion.
AB  - The effect of dietary guar gum (GG, 7.5%) on lipid metabolism and on bile acid
      secretion and reabsorption was investigated in rats adapted to cholesterol-free
      or 0.3% cholesterol diets. Compared with controls (fiber-free/cholesterol-free),
      rats fed cholesterol had significantly elevated plasma and liver cholesterol and
      triglyceride. In these rats, GG had a potent plasma cholesterol-lowering effect
      and also counteracted the liver accumulation of triglyceride and cholesterol
      esters. Fecal excretion of sterols, the major route of cholesterol elimination,
      was markedly enhanced by GG, especially in rats fed the cholesterol-containing
      diet (P < 0.001). The biliary bile acid flux into the small intestine was
      enhanced by dietary cholesterol (+30%) or GG (+52%) or both (P < 0.001). The
      fecal excretion of bile acids was significantly elevated by GG alone (+74%) and
      by dietary cholesterol (+190%). Small intestine reabsorption of bile acids
      appears to be significantly enhanced by GG, which also enhanced the transfer of
      bile acids into the large intestine, hence a greater fecal loss of steroids,
      although bile acid reabsorption was very effective in the cecum. GG feeding
      induced liver hydroxymethyl-glutaryl coenzyme A (HMG CoA) reductase, even in
      cholesterol-fed rats, as well as cholesterol 7 alpha-hydroxylase (P < 0.001). The
      cholesterol-lowering effect of GG thus appears to be mediated by an accelerated
      fecal excretion of steroids and a rise in the intestinal pool and biliary
      production of bile acids. Although liver HMG CoA reductase and cholesterol 7
      alpha-hydroxylase are induced in parallel, this is not sufficient to compensate
      for fecal steroid losses.

PMID- 9187621
TI  - Dietary lipids modulate bone prostaglandin E2 production, insulin-like growth
      factor-I concentration and formation rate in chicks.
AB  - This study examined the effects of dietary fat on the fatty acid composition of
      liver and bone, and on the concentration of insulin-like growth factor-I (IGF-I)
      in liver and bone, as well as the relationship of these factors to bone
      metabolism. Day-old male broiler chicks were given a semipurified diet containing
      one of four lipid sources: soybean oil (SBO), butter+corn oil (BC),
      margarine+corn oil (MAC), or menhaden oil+corn oil (MEC) at 70 g/kg of the diet.
      At 21 and 42 d of age, chicks fed MEC had the highest concentration of (n-3)
      fatty acids [20:5(n-3), 22:5(n-3) and 22:6(n-3)] in polar and neutral lipids of
      cortical bone but the lowest amount of 20:4(n-6) in polar lipids. Diets
      containing t-18:1 fatty acids (MAC and BC) resulted in t18:1 accumulation in bone
      and liver. Bone IGF-I concentration increased from 21 to 42 d in chicks given the
      SBO and BC diets. Tibial periosteal bone formation rate (BFR) was higher in
      chicks given BC compared with those consuming SBO and MEC at 21 d. The higher BFR
      and concentrations of hexosamine in serum and IGF-I in cartilage, but lower
      20:4(n-6) content in bone polar lipids in chicks given BC compared with those
      given SBO suggest that BC optimized bone formation by altering the production of
      bone growth factors. A second study confirmed that dietary butter fat lowered ex
      vivo prostaglandin E2 production and increased trabecular BFR in chick tibia.
      These studies showed that dietary fat altered BFR perhaps by controlling the
      production of local regulatory factors in bone.

PMID- 9187622
TI  - Iron uptake by rabbit intestinal brush border membrane vesicles involves movement
      through the outer surface, membrane interior, inner surface and aqueous interior.
AB  - Iron uptake in rabbit brush border membrane vesicles was measured in the presence
      of nitrilotriacetate. The complexes formed ranged from stable mononuclear species
      to hydrolyzed polynuclear complexes and are considered as a good model for
      nutritional iron compounds with respect to their chemical reactivity. Uptake
      includes both binding to and penetration through the membrane. A strategy was
      developed to localize iron in the following four compartments: outer membrane
      surface, membrane interior, inner membrane surface and aqueous phase within the
      vesicles. Both surfaces as well as the membrane interior revealed a high metal
      binding capacity. After an incubation for 10 min with 182 mumol/L iron and 364
      mumol/L nitrilotriacetate, 35% of total vesicle iron was found to be bound to the
      outer membrane surface, 34% to the inner membrane surface, and 23% was not
      accessible to EDTA. Thus, by adsorption of polynuclear iron complexes to the
      outer surface, the residence time of iron may be prolonged. The remaining 8% of
      total iron was in the aqueous phase within the vesicles. Nitrilotriacetate enters
      the rabbit vesicles in a concentration-dependent manner. As a consequence, iron
      concentration in the aqueous phase within the vesicles will be driven to the
      medium equilibrium concentration.

PMID- 9187623
TI  - Linear growth retardation in Zanzibari school children.
AB  - This paper describes the longitudinal changes in height and weight of children in
      school grades 1-3 on Pemba Island, Zanzibar, a poor rural population in which
      parasitic infections and anemia are highly prevalent. Heights and weights of
      children were measured at base line, and 6 and 12 mo later, and were compared
      with U.S. reference data. At base line, the prevalence of height-for-age Z-score
      < -2 rose from 14% in 7-y-old children to 83% in 13-y-old children. Prevalence of
      weight-for-age Z-score < -2 in children < 10 y was approximately 10% or less.
      Median 6-mo height increments for Pembian boys were around the 5th percentile at
      age 8 and around the 10th percentile from age 9 to 13 y. Height increments for
      girls improved from below the 25th percentile to above the median in this age
      range. Based on the longitudinal yearly gains observed, boys accumulate a height
      deficit of 11.9 cm and girls 8.5 cm, relative to the reference population. In
      multivariate analyses, a small part of the variability in growth increments was
      explained by ascariasis and anemia (for weight gain) and schistosomiasis (for
      height gain). A review of other growth data from rural African Bantu populations
      provides supporting evidence that stunting occurs in older as well as younger
      children. It has been controversial whether school-based health and nutrition
      interventions could induce catch-up growth in already stunted children. Our
      results suggest that appropriate interventions might actually prevent stunting in
      late childhood.

PMID- 9187624
TI  - Development of an approach for estimating usual nutrient intake distributions at
      the population level.
AB  - Assessment of the dietary intake of a population must consider the large within
      person variation in daily intakes. A 1986 report by the National Academy of
      Sciences (NAS), commissioned by the U.S. Department of Agriculture (USDA), marked
      an important milestone in the history of this issue. Since that time, USDA has
      been working cooperatively with statisticians at Iowa State University (ISU), who
      have further developed the measurement error model approach proposed by NAS. The
      method developed by the ISU statisticians can be used to estimate usual dietary
      intake distributions for a population but not for specific individuals. It is
      based on the assumption that an individual can more accurately recall and
      describe the foods eaten yesterday than foods eaten at an earlier time. The
      method requires as few as two independent days of nutrient intake information or
      three consecutive days for at least a subsample of the individuals. It removes
      biases of subsequent reporting days compared with the first day, and temporal
      effects such as day-of-the-week and seasonal effects can be easily removed. The
      method developed at ISU is described conceptually and applied to data collected
      in the 1989-91 USDA Continuing Survey of Food intakes by individuals to estimate
      the proportion of men and women age 20 y and older having "usual" (long-run
      average) intakes below 30% of energy from fat, below the 1989 Recommended Dietary
      Allowances for vitamin A and folate, and above 1000 micrograms for folate. These
      results were compared with the results from the distributions of 1-d intakes and
      of 3-d mean intakes to demonstrate the effect of within-person variation and
      asymmetry on usual nutrient intakes in a population.

PMID- 9187625
TI  - Gestational age and infant size at birth are associated with dietary sugar intake
      among pregnant adolescents.
AB  - The objective of this study was explore the relationship between pregnancy
      outcomes and dietary sugar intake by pregnant adolescents. From two urban,
      prenatal clinics in the City of Camden, NJ, a cohort of 594 nondiabetic, pregnant
      adolescents, aged 13-19 y, who delivered live, singleton newborns between 1985
      and 1990, was recruited and followed through pregnancy. Registered dietitians
      collected up to three 24-h recalls during pregnancy. The adolescents were
      categorized according to total sugar in their diets, with those in the top 10th
      percentile defined as high sugar consumers (> or = 206 g, n = 60) and the
      remainder as reference consumers (< 206 g). Primary outcome measures were birth
      of small-for-gestational-age infants and gestational age. The cohort was 61%
      black, 30% Hispanic (Puerto Rican) and 9% white. The adjusted odds ratio was 2.01
      (95% confidence interval 1.05-7.53) for the delivery of a small-for-gestational
      age infant for adolescents consuming high sugar diets, regardless of their
      ethnicity. In addition, gestational age at delivery was -1.69 +/- 0.62 wk (beta
      +/- SE) shorter among Puerto Rican adolescents consuming high sugar diets (P =
      0.007) compared with all reference sugar consumers and white adolescents
      consuming high sugar diets. Black adolescents consuming high sugar diets did not
      exhibit a shortening of gestation. Thus, adolescents consuming high sugar diets
      are at increased risk for delivering small-for-gestational-age infants, and for
      delivering infants earlier if they are of Puerto Rican ethnicity.

PMID- 9187626
TI  - Protein-energy malnutrition delays small-intestinal recovery in neonatal pigs
      infected with rotavirus.
AB  - Infectious diarrheal diseases and protein-energy malnutrition (PEM) are major
      causes of child morbidity and mortality worldwide. In the present study, PEM was
      superimposed on rotavirus infection in neonatal pigs to simulate chronic small
      intestinal stress in malnourished infants with viral gastroenteritis. Two-day-old
      cesarean-derived pigs (n = 39) were allotted to three treatment groups: 1)
      noninfected, full-fed; 2) infected, full-fed; and 3) infected, malnourished. Two
      days postinfection, severe diarrhea and weight loss (11%) were accompanied by
      reductions in villus height (60%) and lactase activity (78%) and increased crypt
      depth (32%) in infected full-fed compared with noninfected pigs (P < 0.05).
      Malnutrition blunted (P < 0.05) increases in crypt depth elicited by rotavirus.
      By 9 d postinfection, body weight was 59% less, villus height and lactase
      activity remained lower (50%), and crypt depth remained greater (62%) in infected
      full-fed compared with noninfected pigs (P < 0.05). However, diarrhea began to
      clear in infected full-fed, but not in infected malnourished pigs. Plasma insulin
      like growth factor-I (IGF-I) was reduced 68% and crypt depth was reduced 19% in
      infected-malnourished compared with infected full-fed pigs (P < 0.05). Sixteen
      days postinfection, full-fed pigs had recovered from rotaviral infection;
      however, in infected-malnourished pigs, diarrhea and growth stasis persisted, and
      plasma IGF-I, villus height and alkaline phosphatase activity remained reduced
      compared with infected full-fed pigs (P < 0.05). Overall, PEM prolonged diarrhea
      and delayed small-intestinal recovery, indicating that nutritional status during
      diarrhea is essential for recovery from rotaviral enteritis.

PMID- 9187627
TI  - Homoarginine influences voluntary feed intake, tissue basic amino acid
      concentrations and arginase activity in chickens.
AB  - Two experiments were conducted to investigate the factors responsible for the
      adverse effects of guanidinated proteins on feed intake in chickens. In
      Experiment 1, male broiler chicks were fed one of five purified diets containing
      casein or guanidinated casein (G-casein) as the sole source of protein (230 g
      crude protein/kg diet) from d 6 to 13 post-hatching. A casein-based diet
      containing 17.2 g lysine/kg, served as the control. In the experimental diets,
      casein was substituted by G-casein and lysine was added at 0, 5.6, 11.4 and 17.0
      g/kg diet, respectively. Feed intake and weight gains of chicks fed the G-casein
      diet without added lysine were markedly depressed (P < 0.05), but this depression
      was largely overcome by additional lysine. The intake and gains of chicks fed the
      G-casein diet plus 17.0 g lysine/kg were lower (P < 0.05) than those fed the G
      casein diet plus 11.4 g lysine/kg and this was associated with a higher plasma
      lysine:arginine ratio. Tissue analysis showed that homoarginine is distributed
      throughout body tissues following absorption. Brain lysine concentrations were
      lower (P < 0.05) in chicks fed diets containing G-casein without added lysine,
      but increased (P < 0.05) with supplemental lysine. In Experiment 2, the effect of
      homoarginine per se on feed intake was investigated in two short-term intake
      studies using 5-wk-old broiler chickens. Significant (P < 0.05) depressions in
      feed intake were observed within the first hour after oral administration of 400
      mg homoarginine-HCl. The results suggest that both lysine deficiency and
      homoarginine per se were responsible for the adverse effects of guanidinated
      proteins on feed intake in chickens.

PMID- 9187628
TI  - Folate transport proteins mediate the bidirectional transport of 5
      methyltetrahydrofolate in cultured human proximal tubule cells.
AB  - Although reabsorption across the apical (AP) membrane of the renal proximal
      tubule cell plays a vital role in the conservation of plasma 5
      methyltetrahydrofolate, basolateral (BL) membrane-directed secretory pathways may
      also be important in regulating the urinary excretion of folate. Folate transport
      proteins, folate receptor and the reduced folate carrier have been implicated in
      the renal conservation of folate across the AP membrane, but their role in BL
      membrane-directed folate transport has not been studied. 5-Methyltetrahydrofolate
      transport across the AP and BL membranes of human proximal tubule cells was
      studied in cells grown on membrane inserts to allow optimum differentiation of AP
      and BL domains. Colchicine, an inhibitor of vesicular-mediated endocytosis,
      inhibited AP binding and AP-directed transport without affecting BL transport.
      Probenecid, an inhibitor of anion exchange, did not affect binding, but inhibited
      both AP and BL-directed transport with a greater effect on BL transport. Folic
      acid abolished AP binding of 5-methyltetrahydrofolate, but diminished AP-mediated
      transport by only 50%. These data suggest that both the folate receptor and the
      reduced folate carrier participate in AP uptake of folates by human kidney cells,
      but that BL-mediated uptake occurs primarily by the reduced folate carrier.
      Folate transport from the secretory direction occurred as readily as that from
      the reabsorptive direction, indicating that altered secretion could mediate
      excess urinary folate excretion.

PMID- 9187629
TI  - Dietary stearic acid reduces plasma and hepatic cholesterol concentrations
      without increasing bile acid excretion in cholesterol-fed hamsters.
AB  - Although there is general agreement that saturated fatty acids elevate plasma
      cholesterol concentrations, the relative effects of individual fatty acids on
      cholesterol and bile acid metabolism are less clear. In this study, cholesterol
      and bile acid responses to diets enriched in different saturated fatty acids were
      investigated in hamsters. The six diets examined were as follows: 5% fat (g/100
      g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched,
      0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15%
      fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0),
      or stearic acid (18:0). Total plasma cholesterol concentration was significantly
      greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0
      enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of
      hamsters fed 18:0 did not differ from those of the group fed no dietary
      cholesterol. In all instances, differences in total plasma cholesterol were
      accounted for within the HDL fraction; no significant treatment differences in
      VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was
      higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary
      cholesterol (P < 0.05), but not significantly different from other treatment
      groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed
      the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small
      intestinal + gallbladder bile acids, an index of pool size, did not differ
      significantly among the groups. The observed relative hypocholesterolemic effect
      of stearic acid was not mediated by increased bile acid excretion.

PMID- 9187630
TI  - Protein synthesis and degradation change rapidly in response to food intake in
      muscle of food-deprived mice.
AB  - The short-term changes in muscle protein synthesis and degradation after food
      intake are unclear. We investigated muscle protein metabolism after food intake
      in mice that were starved for 18 h and refed for 1 h. Protein synthesis activity
      was estimated by the polysome profiles, and protein degradation was estimated by
      plasma N tau-methylhistidine (MeHis) concentration, reflecting translational
      activity and myofibrillar protein degradation, respectively. MeHis is an index of
      myofibrillar protein degradation because it is not reused for protein synthesis
      and it is not metabolized. Stimulation of protein synthesis (polysome profile)
      and the reduction of protein degradation (plasma N tau-methylhistidine
      concentration) were observed immediately after feeding began. Protein synthesis
      returned to the prefeeding level by 6 h after refeeding, whereas protein
      degradation remained at a low level. The decreased plasma MeHis concentration
      after refeeding was not due to a decrease in MeHis release from muscle cells and
      an increase in the free MeHis pool size, because the changes in free MeHis
      concentration in muscle were similar to that of plasma. Plasma insulin
      concentration immediately rose with feeding and it returned to the prefeeding
      level by 3 h after refeeding. These results suggest that responses of
      postprandial protein metabolism are very rapid and that protein synthesis is
      regulated by insulin, whereas degradation is regulated by insulin and other
      dietary factors. Thus the ability of skeletal muscle to use nutrients more
      effectively by stimulating protein synthesis and reducing protein degradation may
      cause the accelerated rate of protein accretion in skeletal muscle during the
      short postprandial period.

PMID- 9187631
TI  - [15N]-labeled pea flour protein nitrogen exhibits good ileal digestibility and
      postprandial retention in humans.
AB  - The aim of the present study was to evaluate postprandial absorption of pea
      protein as well as exogenous nitrogen retention in humans. For this purpose,
      after fasting overnight, seven healthy adults (4 males and 3 females) ingested
      [15N]-labeled pea protein (195 mmol N). Ileal effluents were collected for 8 h at
      30-min intervals using a nasointestinal intubation technique. Urine and plasma
      samples were collected for 24 h. The [15N]-enrichment was determined in the
      intestinal samples, in the plasma amino acids and urea as well as in the urinary
      urea and ammonia fractions. The true gastroileal absorption of pea protein was
      89.4 +/- 1.1%. This absorption was correlated with a significant increase (P <
      0.05) in [15N]-enrichment in the plasma amino acids and in the nitrogen
      incorporated into the body urea pool for 1 h following pea ingestion. The
      enrichment remained significantly higher than the basal values in these pools 24
      h after pea ingestion. The recovery of total urinary exogenous nitrogen after 22
      h was 31.1 +/- 9.3 mmol N. Moreover, the kinetics of [15N]-labeled pea amino
      acids deamination reached a plateau of 39 mmol. Under these conditions, pea
      nitrogen retention represented 78% of the absorbed dietary nitrogen in healthy
      humans. The present results demonstrate the good true nitrogen digestibility and
      retention of pea protein in humans.

PMID- 9187632
TI  - Response of rainbow trout (Oncorhynchus mykiss) to supplements of individual
      essential amino acids in a semipurified diet, including an estimate of the
      maintenance requirement for essential amino acids.
AB  - We studied the effects of increasing dietary concentrations of each of the
      following amino acids on growth, feed intake, feed conversion ratio and
      composition of gain in rainbow trout in six dose-response experiments: L-lysine,
      L-tryptophan, L-histidine, L-valine, L-leucine and L-isoleucine. Semipurified
      diets containing 20.1 MJ digestible energy/kg dry matter, with wheat gluten and
      crystalline amino acids as sole sources of amino acids, were fed to rainbow trout
      [initial mean body weight (BW) 40-51 g, depending on the amino acid studied]. In
      one series of 24 diets, lysine concentration ranged from 4.5 to 58.0 g/kg dry
      matter; in five further series of 12 diets each, concentrations ranged from (in
      g/kg dry matter): tryptophan, 1.3 to 5.6; histidine, 2.6 to 13.5; valine, 6.2 to
      34.2; leucine, 10.0 to 42.0 and isoleucine, 5.0 to 15.3. Each diet was fed to a
      group of 20 fish for 53-64 d, depending on the amino acid studied. Dry matter
      intake, weight gain, feed conversion ratio, protein concentration of gain and
      total protein deposition followed exponential response functions. To achieve 95%
      of the maximum protein deposition, dietary concentrations of 27.7 g lysine, 2.0 g
      tryptophan, 5.8 g histidine, 15.7 g valine, 13.6 g leucine and 13.7 g
      isoleucine/kg dry matter were required. Maintenance requirements, estimated from
      exponential functions for protein deposition, were [in mg/(100 g BW.d)]: lysine,
      1.93; tryptophan, 1.05; histidine, 1.07; valine, 2.92; leucine, 8.26 and
      isoleucine, 0.91. This corresponds to 4% of the requirement for protein
      deposition for lysine and isoleucine but 32% for leucine, with the other amino
      acids being intermediate. Therefore, different dietary amino acid requirement
      patterns were derived from protein deposition data depending on the chosen level
      of performance.

PMID- 9187633
TI  - Dietary vegetable oils and alpha-tocopherol reduce lipid oxidation in rabbit
      muscle.
AB  - This experiment was conducted to study the effect of dietary vegetable oil on
      lipid oxidation in rabbit muscle. A control diet with no added fat and two diets
      with olive or sunflower oil (30 g/kg) were used. Within each treatment, one group
      was fed a low level of alpha-tocopheryl acetate (10 mg/kg diet), and the other a
      supplemental level (200 mg/kg). Rabbits were fed experimental diets from weaning
      (20 d) to slaughter (69 d). The supplemental level of dietary alpha-tocopheryl
      acetate produced higher alpha-tocopherol concentration in muscle (P < 0.006) and
      lower lipid oxidation (P < 0.004). Rabbits that received sunflower oil had higher
      concentrations of thiobarbituric acid reactive substances than rabbits that
      consumed olive oil (P < 0.05). Moreover, a significant effect due to fat
      inclusion in the diet was found. Muscles from rabbits fed diets not enriched with
      fat had higher susceptibility to lipid oxidation (P < 0.005) and higher
      concentration of (n-3) fatty acids in polar lipids (P < 0.04) than those from
      rabbits fed fat-enriched diets. A second experiment was conducted and confirmed
      the higher lipid oxidation in the muscle of rabbits fed diets not enriched with
      fat than in that of rabbits fed diets containing sunflower oil (28 g/kg) (P <
      0.003) as well as in diets with identical digestible energy. In this experiment,
      alpha-tocopheryl acetate was at the lower level (10 mg/kg feed). Inclusion of
      oils rich in oleic (olive oil) or linoleic acid (sunflower oil) in rabbit diets
      reduces lipid oxidation in muscles.

PMID- 9187634
TI  - The efflux of lysine from the basolateral membrane of human cultured intestinal
      cells (Caco-2) occurs by different mechanisms depending on the extracellular
      availability of amino acids.
AB  - The efflux of the nutritionally essential amino acid, L-lysine from the
      basolateral (BL) membrane was characterized in human cultured intestinal cells
      (Caco-2) grown and differentiated on permeable filter supports. Cells were loaded
      by incubating with 3H-lysine from the apical (AP) side in the absence of sodium
      (substituted with choline) in the BL medium; under these conditions, cells
      accumulated lysine in the intracellular soluble pool to 10- to 20-fold the
      extracellular concentration. L-Lysine efflux in the BL medium was then followed,
      and initial rates of efflux were calculated under different experimental
      conditions. L-Lysine efflux exhibited a strong energy dependence. The presence of
      an inwardly directed gradient of sodium or lithium stimulated lysine efflux;
      ouabain reduced efflux in both sodium- and lithium-containing medium. When
      zwitterionic or cationic amino acids were added to the BL medium, L-lysine efflux
      was strongly stimulated. The most efficient trans-stimulating amino acids were L
      leucine > L-methionine = L-ornithine = L-arginine. In the presence of trans
      stimulating amino acids in the BL medium, L-lysine efflux exhibited energy
      independence and was not affected by the presence of a sodium gradient. In
      addition, the sensitivity, of efflux to N-ethylmaleimide was different in the
      absence or in the presence of amino acids in the BL medium. These results suggest
      that different mechanisms may operate in the BL efflux of L-lysine from human
      intestinal epithelial cells, depending on the extracellular availability of other
      amino acids, to guarantee optimal bioavailability of this essential amino acid
      both in the postprandial absorptive period and between meals.

PMID- 9187635
TI  - Pancreatic islet transplantation improves body composition, decreases energy
      intake and normalizes energy efficiency in previously diabetic female rats.
AB  - We investigated the weight gain, body composition, and feed efficiency of female
      Wistar Furth rats (170 +/- 1 g) made diabetic with streptozotocin (55 mg/kg
      intravenously), then infused intraportally with 3519 +/- 838 (150 mu equivalent
      units) syngeneic pancreatic islets of Langerhans. After islet transplants (5-6
      wk), nutritional energetics were evaluated in transplanted rats (Transplant), and
      also in 3- and 9-wk diabetic (Diab-3, 9) and control rats treated with sham
      infusions and similar surgical manipulations (Sham-3, 9). Diabetic rats
      demonstrated marked hyperphagia, which was corrected by islet transplantation
      (577 +/- 53 vs. 266 +/- 19 kJ/d; P < 0.0001) and was not different than sham
      control rats (285 +/- 24 kJ/d; P > 0.05). Three weeks of diabetes resulted in a
      lower protein (Diab-3, 24.8 +/- 2.6 g vs. Sham-3, 30.9 +/- 1.0 g) and fat content
      (1.9 +/- 0.8 g vs. 11.6 +/- 1.7 g) in the rats' carcasses. However, 6 wk after
      islet transplantation, rats receiving islets (Transplant) were not different than
      control rats (Sham-9) (31.9 +/- 1.7 g vs. 33.3 +/- 1.9 g protein and 15.4 +/- 3.0
      g vs. 15.1 +/- 3.2 g fat). Three weeks of diabetes resulted in a lesser energy
      efficiency compared with Sham rats (2.7 +/- 2.0 vs. 7.1 +/- 1.9 kJ gained/100 kJ
      ingested); islet-transplanted rats were not different than Sham-9 rats (4.9 +/-
      2.3 vs. 4.7 +/- 1.4 kJ gained/100 kJ ingested). These data illustrate that islet
      transplantation in previously diabetic female rats improves growth with
      proportional gains in body protein and fat mass. This is modulated in part by a
      reduced food intake and an energy efficiency that is improved relative to
      controls. These studies offer an optimistic outlook for the continued development
      of more physiological insulin delivery strategies that preclude the nutritional
      complications associated with exogenous insulin administration.

PMID- 9187636
TI  - The ratio of dietary (n-6) to (n-3) fatty acids influences immune system
      function, eicosanoid metabolism, lipid peroxidation and vitamin E status in aged
      dogs.
AB  - We studied the effects of feeding experimental diets containing (n-6) to (n-3)
      fatty acid ratios of 31:1, 5.4:1, and 1.4:1 to 20 healthy female geriatric
      Beagles (9.5-11.5 y) for 8-12 wk on various indices of the immune response.
      Compared with the 31:1 diet, consumption of the 5.4:1 and 1.4:1 diets
      significantly increased (n-3) fatty acids in plasma (2.17 +/- 0.64, 9.05 +/-
      0.64, 17.46 +/- 0.64 g/100 g fatty acids, respectively, P < 0.0001). Although
      supplementation with (n-3) fatty acids did not significantly alter the humoral
      immune response to keyhole limpet hemocyanin (KLH), it significantly suppressed
      the cell-mediated immune response based on results of a delayed-type
      hypersensitivity (DTH) skin test. The DTH response after intradermal injection of
      KLH at 24 h was significantly lower in the group consuming the 1.4:1 diet
      compared with the group consuming the 5.4:1 (P = 0.02) or the 31:1 diets (P =
      0.04), and remained significantly suppressed at 48 h in the group fed 1.4:1
      relative to the group fed 31:1. After consumption of the 1.4:1 diet, stimulated
      mononuclear cells produced 52% less prostaglandin E2 (PGE2) than those from dogs
      fed the 31:1 diet (224 +/- 74 and 451 +/- 71 pmol/L, respectively, P = 0.04).
      Plasma concentration of alpha-tocopherol was 20% lower in dogs fed the 1.4:1 diet
      compared with those fed the 31:1 diet (P = 0.04), and lipid peroxidation was
      greater in both plasma (P = 0.03) and urine (P = 0.002). These data suggest that
      although a ratio of dietary (n-6) to (n-3) fatty acids of 1.4:1 depresses the
      cell-mediated immune response and PGE2 production, it increases lipid
      peroxidation and lowers vitamin E concentration.

PMID- 9187637
TI  - Oscillatory potentials and light microscopic changes demonstrate an interaction
      between zinc and taurine in the developing rat retina.
AB  - Our objective was to investigate whether zinc interacts with taurine to influence
      the development of retinal structure and function. Virgin female Sprague-Dawley
      rats were bred overnight and assigned to one of four treatments in a 2 x 2
      factorial design with two levels of zinc (50 micrograms/g through gestation and
      50 micrograms/g after parturition; 15 micrograms/g through gestation and 7.5
      micrograms/g after parturition) and two levels of taurine (2 or 0 mumol/g). The
      control diet contained 50 micrograms/g zinc and 2 mumol/g taurine. Guanidinoethyl
      sulfonate (10 g/L), a taurine transport inhibitor, was added to the drinking
      water of the rats receiving 0 mumol/g taurine. At postnatal d 23, male pups (n =
      10) were weaned onto their respective diets. Pup eyes were examined by
      biomicroscope and indirect ophthalmoscope at 4 and 7 wk; retinal folds and
      choroidal atrophy were detected in the pups deficient in zinc and taurine.
      Analysis of plasma zinc and tibial zinc concentrations revealed a significant
      interaction in these tissues (P < 0.05). Dark-adapted oscillatory potentials (OP)
      were recorded at 7.5-8.5 wk. Two-way ANOVA showed a significant interaction
      between zinc and taurine for OP2 and OP3 amplitudes; marginal zinc deficiency
      decreased the amplitude of the OP only when rats were also deficient in taurine.
      A significant depressing effect of marginal zinc deficiency was noted for OP1
      amplitude. Taurine deficiency significantly depressed the amplitude of OP1 and
      OP4. Histological examination of the retinas from rats deficient in both zinc and
      taurine revealed photoreceptor degeneration and confirmed retinal dysplasia.
      These data provide evidence for an interaction between zinc and taurine in
      retinal morphology and function.

PMID- 9187638
TI  - Dietary Iodine and selenium interact to affect thyroid hormone metabolism of
      rats.
AB  - The interaction of dietary selenium and iodine on the activities of the
      selenoenzymes, selenium-dependent glutathione peroxidase (GSH-Px), and type I
      deiodinase (DI-I), and the thyroid hormones thyroxine (T4) and triiodothyronine
      (T3) were studied. Male weanling Sprague-Dawley rats were fed an AIN-93G diet for
      6 wk with modified selenium and iodine concentration as follows: three levels
      each of iodine and selenium (0.03, 0.2 added and 1.0 added mg iodine/kg diet, and
      0.05, 0.18 added and 1.0 added mg selenium/kg diet) were used in a 3 x 3
      factorial design. Renal, but not hepatic, DI-I activity was lower in rats with
      low selenium intake than in controls. Circulating T3 concentration was not
      affected by the dietary levels of iodine or selenium. Unlike in liver, kidney and
      erythrocytes, thyroidal GSH-Px activity was not lower than in controls in rats
      with low selenium intake, but was significantly higher when iodine intake was
      low. Significant interactions of iodine and selenium on serum T4 and thyroidal
      GSH-Px activity were observed. Serum T4 was maintained at control levels when
      both dietary iodine and selenium were low, but not when iodine alone, or selenium
      alone, was low. Activity of thyroidal GSH-Px was lowest in rats fed a diet
      containing high iodine and low selenium. The results suggest that high iodine
      intake, when selenium is deficient, may permit thyroid tissue damage as a result
      of low thyroidal GSH-Px activity during thyroid stimulation. A moderately low
      selenium intake normalized circulating T4 concentration in the presence of iodine
      deficiency.

PMID- 9187639
TI  - Chronic exercise affects vitamin B-6 metabolism but not requirement of growing
      rats.
AB  - The effect of chronic exercise (forced swimming) on vitamin B-6 status and
      metabolism was studied in growing male rats fed deficient (0 mg pyridoxine
      HCl/kg), suboptimal (2 mg pyridoxine-HCl/kg) or control (7 mg pyridoxine-HCl/kg)
      diets for 9 wk. Sedentary rats were fed the same diets. Body weight gain was
      lower in deficient rats than in both other dietary groups. Sedentary rats were
      heavier than trained rats of all diet groups. Erythrocyte aspartate
      aminotransferase, urinary 4-pyridoxic acid excretion, blood (plasma and
      erythrocytes) and tissue B-6 vitamers were measured. Urinary 4-pyridoxic acid,
      plasma pyridoxal 5'-phosphate and erythrocyte aspartate aminotransferase values
      of exercised and sedentary rats responded to changes in dietary pyridoxine but
      were not different from one another. After 9 wk of vitamin B-6 depletion, tissue
      concentrations of pyridoxal 5'-phosphate and pyridoxamine 5;5'-phosphate were 41
      66% and 26-49% lower, respectively, in the deficient groups than in the control
      groups. Larger percentage differences occurred in plasma than in tissues (95 vs.
      22-66%). In liver, pyridoxal 5'-phosphate concentrations were lower, whereas
      pyridoxal concentrations were higher in trained than in sedentary rats. In
      gastrocnemius muscle, pyridoxal 5'-phosphate, pyridoxamine 5'-phosphate and total
      vitamin B-6 concentrations were higher in trained than in sedentary rats.
      Concentrations of vitamin B-6 compounds in heart, kidneys, brain and adrenals
      were not affected by training. On the basis of the vitamin B-6-dependent
      variables measured in this study, we conclude that prolonged exercise affects the
      metabolism of vitamin B-6, but does not increase the vitamin B-6 requirement in
      growing rats.

PMID- 9187640
TI  - Description of a model integrating protein and energy metabolism in preruminant
      calves.
AB  - This paper describes the development of a mechanistic model integrating protein
      and energy metabolism in preruminant calves of 80-240 kg live weight. The
      objectives of the model are to gain insight into the partitioning of nutrients in
      the body of growing calves and to provide a tool for the development of feeding
      strategies for calves in this weight range. The model simulates the partitioning
      of nutrients from ingestion through intermediary metabolism to growth, consisting
      of accretions of protein, fat, ash and water. The model contains 10 state
      variables, comprising fatty acids, glucose, acetyl-CoA and amino acids as
      metabolite pools, and fat, ash and protein in muscle, hide, bone and viscera as
      body constituent pools. Turnover of protein and fat is represented. The model
      also includes a routine to check possible dietary amino acid imbalance and can be
      used to predict amino acid requirements on a theoretical basis. The model is
      based on two experiments, specifically designed for this purpose. Simulations of
      protein and fat accretion rates over a wide range of nutrient input suggest that
      the model is sound. In can be used as a research tool and for the development of
      feeding strategies for preruminant calves.

PMID- 9187642
TI  - Donepezil (Aricept) for Alzheimer's disease.

PMID- 9187641
TI  - Evaluation of a model integrating protein and energy metabolism in preruminant
      calves.
AB  - In a companion paper, a mechanistic model is described, integrating protein and
      energy metabolism in preruminant calves of 80-240 kg live weight. The model
      simulates the partitioning of nutrients from ingestion through intermediary
      metabolism to growth, consisting of accretions of protein, fat, ash and water.
      The model also includes a routine to check possible dietary amino acid imbalance
      and can be used to predict amino acid requirements. This paper describes a
      sensitivity and behavioral analysis of the model, as well as tests against
      independent data. Increasing the carbohydrate:fat ratio at equal gross energy
      intakes leads to higher simulated protein- and lower simulated fat-deposition
      rates. Simulation of two experiments, not used for the development of the model,
      showed that rates of gain of live weight, protein and fat were predicted
      satisfactorily. The representation of protein turnover enables the investigation
      of the quantitative importance of hide, bone and visceral protein in protein and
      energy metabolism. The model is highly sensitive to 25% changes in kinetic
      parameters describing muscle protein synthesis and amino acid oxidation.
      Comparing simulated with experimentally derived amino acid requirements shows
      agreement for most amino acids for calves of approximately 90 kg live weight. For
      calves of approximately 230 kg live weight, however, lower requirements for
      lysine and for methionine+cystine are suggested by the model. More attention has
      to be paid to the inevitable oxidative losses of amino acids. It is concluded
      that the model provides a useful tool for the development of feeding strategies
      for preruminant calves in this weight range.

PMID- 9187643
TI  - Antibiotics and RNA.

PMID- 9187644
TI  - Homing in on intron-encoded endonucleases.

PMID- 9187645
TI  - Nature's transitory covalent bond.

PMID- 9187646
TI  - Solving the cis/trans paradox in the Int family of recombinases.
AB  - Structures of the catalytic domains of lambda Int and HP1 integrase provide
      insight into the diversity of the Int family of recombinases, which nevertheless
      catalyse very similar chemical events.

PMID- 9187647
TI  - Capturing the misfolds: chaperone-peptide-binding motifs.

PMID- 9187648
TI  - X-ray structure of glial cell-derived neurotrophic factor at 1.9 A resolution and
      implications for receptor binding.
AB  - The crystal structure of glial cell-derived neurotrophic factor (GDNF) reveals
      two independent copies of the dimer that differ significantly through a hinge
      bending at the central, disulphide-rich region. GDNF is compared with other
      members of the TGF-beta family, and potential receptor binding surfaces are
      identified.

PMID- 9187649
TI  - Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type
      lectin domains.
AB  - Coagulation factors IX/X-binding protein is an intertwined dimer with a central
      loop projecting into the adjoining subunit. Excluding this loop, each subunit has
      a fold similar to rat mannose-binding protein.

PMID- 9187650
TI  - Picture story. HIV-1 fusion core.

PMID- 9187651
TI  - Defining long range order in NMR structure determination from the dependence of
      heteronuclear relaxation times on rotational diffusion anisotropy.
AB  - Structure determination by NMR presently relies on short range restraints between
      atoms in close spatial proximity, principally in the form of short (< 5 A)
      interproton distances. In the case of modular or multidomain proteins and linear
      nucleic acids, the density of short interproton distance contacts between
      structural elements far apart in the sequence may be insufficient to define their
      relative orientations. In this paper we show how the dependence of heteronuclear
      longitudinal and transverse relaxation times on the rotational diffusion
      anisotropy of non-spherical molecules can be readily used to directly provide
      restraints for simulated annealing structure refinement that characterize long
      range order a priori. The method is demonstrated using the N-terminal domain of
      Enzyme I,a protein of 259 residues comprising two distinct domains with a
      diffusion anisotropy(Dparallel/Dperpendicular)of approximately 2.

PMID- 9187652
TI  - Disulphide-bonded intermediate on the folding and assembly pathway of a non
      disulphide bonded protein.
AB  - The trimeric parallel beta-coil P22 tailspike contains eight cysteines per chain,
      but lacks disulphide bonds in the native state, in both the crystalline and
      solution forms. However, cysteines in a folding intermediate are reactive with
      thiol blocking reagents, which prevent further productive folding both in vivo
      and in vitro. The in vivo refolding yield was independent of the availability of
      metal ions, but was sensitive to redox potential. Isolation by nondenaturing gel
      electrophoresis of the protrimer intermediate, a trimeric folding intermediate
      that precedes the fully folded trimer in the in vivo and in vitro pathways,
      revealed the presence of interchain disulphide bonds. Incubation of the isolated
      protrimer with reducing agents generated the native trimer. The formation of beta
      sheets with interdigitated strands from different subunits in the native trimer
      may require the transient disulphide bonds for proper alignment. To our knowledge
      this is the first report of a disulphide bond present in a folding intermediate
      of a non-disulphide bonded protein.

PMID- 9187653
TI  - Structure of a specific acyl-enzyme complex formed between beta-casomorphin-7 and
      porcine pancreatic elastase.
AB  - Mass spectrometric screening reveals that an unmodified natural heptapeptide-
      human beta-casomorphin-7, an internal sequence of human beta-casein that
      possesses opioid-like activity--reacts with porcine pancreatic elastase to form
      an unusually stable acyl-enzyme complex at low pH. X-ray crystallographic
      analysis (to 1.9 A resolution) at pH 5 shows continuous electron density linking
      the C-terminal isoleucine of beta-casomorphin-7 to Ser 195 through an ester bond.
      The structure reveals a well defined water molecule (Wat 317), equidistant
      between the carbon of the ester carbonyl and N epsilon 2 of His 57. Deprotonation
      of Wat 317 will produce a hydroxide ion positioned to attack the ester carbonyl
      through the favoured Burgi-Dunitz trajectory.

PMID- 9187654
TI  - Structure of the hepatitis C virus RNA helicase domain.
AB  - Helicases are nucleotide triphosphate (NTP)-dependent enzymes responsible for
      unwinding duplex DNA and RNA during genomic replication. The 2.1 A resolution
      structure of the HCV helicase from the positive-stranded RNA hepatitis C virus
      reveals a molecule with distinct NTPase and RNA binding domains. The structure
      supports a mechanism of helicase activity involving initial recognition of the
      requisite 3' single-stranded region on the nucleic acid substrate by a conserved
      arginine-rich sequence on the RNA binding domain. Comparison of
      crystallographically independent molecules shows that rotation of the RNA binding
      domain involves conformational changes within a conserved TATPP sequence and
      untwisting of an extended antiparallel beta-sheet. Location of the TATPP sequence
      at the end of an NTPase domain beta-strand structurally homologous to the 'switch
      region' of many NTP-dependent enzymes offers the possibility that domain rotation
      is coupled to NTP hydrolysis in the helicase catalytic cycle.

PMID- 9187655
TI  - The structure of I-Crel, a group I intron-encoded homing endonuclease.
AB  - The structure of I-Crel provides the first view of a protein encoded by a gene
      within an intron. This endonuclease recognizes a long DNA site approximately 20
      base pairs in length and facilitates the lateral transfer of that intron. The
      protein exhibits a DNA-binding surface consisting of four antiparallel beta
      strands that form a 20 A wide groove which is over 70 A long. The architecture of
      this fold is different from that of the TATA binding protein, TBP, which also
      contains an antiparallel beta-saddle. The conserved LAGLIDADG motif, which is
      found in many mobile intron endonucleases, maturases and inteins, forms a novel
      helical interface and contributes essential residues to the active site.

PMID- 9187656
TI  - A molecular clamp in the crystal structure of the N-terminal domain of the yeast
      Hsp90 chaperone.
AB  - Hsp90 is a highly specific chaperone for many signal transduction proteins,
      including steroid hormone receptors and a broad range of protein kinases. The
      crystal structure of the N-terminal domain of the yeast Hsp90 reveals a dimeric
      structure based on a highly twisted sixteen stranded beta-sheet, whose topology
      suggests a possible 30-domain-swapped structure for the intact Hsp90 dimer. The
      opposing faces of the beta-sheets in the dimer define a potential peptide-binding
      cleft, suggesting that the N-domain may serve as a molecular 'clamp' in the
      binding of ligand proteins to Hsp90.

PMID- 9187657
TI  - Solution structure of an rRNA methyltransferase (ErmAM) that confers macrolide
      lincosamide-streptogramin antibiotic resistance.
AB  - The Erm family of methyltransferases is responsible for the development of
      resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics.
      These enzymes methylate an adenine of 23S ribosomal RNA that prevents the MLS
      antibiotics from binding to the ribosome and exhibiting their antibacterial
      activity. Here we describe the three-dimensional structure of an Erm family
      member, ErmAM, as determined by NMR spectroscopy. The catalytic domain of ErmAM
      is structurally similar to that found in other methyltransferases and consists of
      a seven-stranded beta-sheet flanked by alpha-helices and a small two-stranded
      beta-sheet. In contrast to the catalytic domain, the substrate binding domain is
      different from other methyltransferases and adopts a novel fold that consists of
      four alpha-helices.

PMID- 9187658
TI  - Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate
      synthase.
AB  - Sulfonamides were amongst the first clinically useful antibacterial agents to be
      discovered. The identification of sulfanilamide as the active component of the
      dye Prontosil rubrum led to the synthesis of clinically useful analogues. Today
      sulfamethoxazole (in combination with trimethoprim), is used to treat urinary
      tract infections caused by bacteria such as Escherichia coli and is also a first
      line treatment for pneumonia caused by the fungus Pneumocystis carinii, a common
      condition in AIDS patients. The site of action is the de novo folate biosynthesis
      enzyme dihydropteroate synthase (DHPS) where sulfonamides act as analogues of one
      of the substrates, para-aminobenzoic acid (pABA). We report here the crystal
      structure of E.coli DHPS at 2.0 A resolution refined to an R-factor of 0.185. The
      single domain of 282 residues forms an eight-stranded alpha/beta-barrel. The 7,8
      dihydropterin pyrophosphate (DHPPP) substrate binds in a deep cleft in the
      barrel, whilst sulfanilamide binds closer to the surface. The DHPPP ligand site
      is highly conserved amongst prokaryotic and eukaryotic DHPSs.

PMID- 9187659
TI  - Solution structure of an extracellular domain containing the WSxWS motif of the
      granulocyte colony-stimulating factor receptor and its interaction with ligand.
AB  - We have determined the NMR structure of a ligand-binding domain of the
      granulocyte colony-stimulating factor (G-CSF) receptor, containing the highly
      conserved WSxWS motif. The domain consists of seven beta-strands with the
      fibronectin type III-like topology seen in several cytokine receptors.
      Comparisons between the spectra of the 15N-labelled domain with and without G-CSF
      indicate that the major ligand-recognition site is on the FG loop just upstream
      of the WSxWS sequence, and not on the BC loop which is mainly used in the growth
      hormone system. The WSxWS residues are suggested to contribute to ligand
      recognition and to the protein architecture of the G-CSF receptor.

PMID- 9187660
TI  - Exclusion of the expansion of CAG/CTG repeats at thirteen loci on chromosome 12
      as a candidate genetic mutation in scapuloperoneal spinal muscular atrophy with
      anticipation.
AB  - Scapuloperoneal spinal muscular atrophy (SPSMA) is a neuromuscular disorder
      characterized by weakness in the distribution of shoulder girdle and peroneal
      muscles. We have previously described a large New England kindred with autosomal
      dominant SPSMA and have subsequently linked this family trait to 12q24.1-q24.31.
      In this family, disease expression becomes more severe and progressive in
      successive generations, suggesting genetic anticipation. Accordingly, we have
      investigated the thirteen known CAG/CTG repeat loci on chromosome 12 that could
      be tested by using the polymerase chain reaction as candidate genetic mutations
      in SPSMA. None of these loci is expanded.

PMID- 9187661
TI  - A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase may
      impair redox partner interaction.
AB  - Lesions in the gene encoding steroid 21-hydroxylase result in congenital adrenal
      hyperplasia, with impaired secretion of cortisol and aldosterone from the adrenal
      cortex and overproduction of androgens. A limited number of mutations account for
      the majority of mutated alleles, but additional rare mutations are responsible
      for the symptoms in some patients. A total of 11 missense mutations has
      previously been implicated in this enzyme deficiency. We describe two novel
      missense mutations, both affecting the same amino acid residue, Arg356. The two
      mutations, R356P and R356Q, were reconstructed by in vitro site-directed
      mutagenesis, the proteins were transiently expressed in COS-1 cells, and enzyme
      activity towards the two natural substrates, 17-hydroxyprogesterone and
      progesterone, was determined. The R356P mutant reduced enzyme activity to 0.15%
      towards both substrates, whereas the R356Q mutant exhibited 0.65% of normal
      activity towards 17-hydroxyprogesterone, and 1.1% of normal activity towards
      progesterone. These activities correspond to the degrees of disease manifestation
      of the patients in whom they were found. Arg356 is located in a region which
      recently has been implicated in redox partner interaction, by modelling the
      structure of two other members of the cytochrome P450 superfamily. Of the 11
      previously described missense mutations, three affect arginine residues within
      this protein domain. With the addition of R356P and R356Q, there is a clear
      clustering of five mutations to three closely located basic amino acids. This
      supports the model in which this protein domain is involved in redox partner
      interaction, which takes places through electrostatic interactions between
      charged amino acid residues.

PMID- 9187662
TI  - The role of oxygen metabolism for the pathological phenotype of Fanconi anemia.
AB  - The molecular defect of the hereditary disease Fanconi anemia (FA) remains
      unknown. The two theoretical possibilities are (1) an impaired DNA crosslink
      repair system or (2) a disturbed oxygen metabolism either by overproduction of
      reactive oxygen intermediates (ROI) or by diminished detoxification of ROI. In
      order to gain further insight into the molecular mechanism of this disease, we
      have determined the repair capacity of FA cells challenged by crosslinking agents
      and have analyzed diverse biological systems that are involved in oxygen
      metabolism. We have tested normal and FA cells for oxygen consumption and for the
      activity of the antioxidant phospholipid-hydroperoxide-glutathione-peroxidase
      (PHGPx). FA cells show a reduced oxygen consumption and an increased PHGPx
      activity. Since spontaneous and induced chromosomal instability is a main
      cellular feature of FA, we have analyzed the redox state of cells and the effect
      of cytochrome P-450 (Cyt P-450) inhibitors and inducers on chromosomal breaks and
      micronuclei production. Our results indicate that Cyt P-450 enzymes, especially
      Cyt P-450 1A2, play a crucial role in radical metabolism in FA cells.
      Furthermore, we have determined NF-kappa B activity in untransformed cells and in
      SV40-transformed cells by gel shift experiments. NF-kappa B is a multiunit
      transcription factor that is known to be induced by ROI and that activates the
      expression of various genes involved in cellular responses to stress. NF-kappa B
      is constitutively induced in SV40-transformed FA cells probably as a consequence
      of an increased ROI level. Our results suggest that enzymatic defects in oxygen
      metabolism mediate the FA phenotype via impaired reactivity with ROI. Cyt P-450
      1A2 appears to be a good candidate for the defective enzyme, even though no
      differences have been measured in the activity of this enzyme in FA and control
      fibroblasts in pilot experiments.

PMID- 9187663
TI  - Identification of de novo deletions at the NF1 gene: no preferential paternal
      origin and phenotypic analysis of patients.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. To date,
      a relatively small number of NF1 mutations have been characterized, thus
      precluding genotype-phenotype correlations. By genotyping 75 NF1 families, we
      have detected six hemizygous patients (two of whom are members of the same
      family). The five presumed deletions were confirmed by two quantitative methods
      of analysis of NF1 copy number: Southern hybridization with cDNA probes and a
      single-strand conformation polymorphism analysis that discriminates between the
      NF1 gene and the pseudogene sequences. The five deletions remove most of the NF1
      gene, at least 225 kb, from exon 9 to the 3' end of the coding sequence. The
      origin of de novo mutations in the NF1 gene has been reported to be mainly
      paternal but we have determined that four of the de novo deletions involved the
      maternal chromosome and one the paternal chromosome. The six patients with
      deletions exhibited precocious, multiple clinical features of the disease. The
      incidence of tumor complications, particularly plexiform neurofibromas and
      intracranial tumors, among this group of patients is higher than the observed
      incidence in our NF1 population, suggesting that NF1 haploinsufficiency may cause
      a more severe phenotype with regard to tumor development. In contrast to other
      reports that associated large deletions with mildly dysmorphic facies, mental
      retardation and a large number of cutaneous neurofibromas, only one out of our
      six patients presented this phenotype.

PMID- 9187664
TI  - DNA polymorphisms in the 5'-flanking region of the human tissue kallikrein gene.
AB  - Human tissue kallikrein gene polymorphisms were identified in the promoter region
      by polymerase chain reaction (PCR) and DNA sequencing. One polymorphic region was
      identified between nucleotides -121 and -133 with respect to the transcription
      initiation site of the tissue kallikrein gene. Ten alleles with length and
      nucleotide sequence variations were detected among 108 unrelated Caucasians,
      African-Americans, and Asians. The polymorphisms show Hardy-Weinberg equilibrium.
      Allele-specific amplification and PCR analyses were used to detect the various
      forms of polymorphism. The promoter activity was analyzed in human embryonic
      kidney 293 cells by transient transfection assays. Sequential 5'-deletion
      analysis of the tissue kallikrein gene promoter revealed that the region from 
      144 to -98 is crucial for its promotor activity, while alleles D and H had
      significantly lower promoter activities than the other alleles in the -940/+10
      deletion constructs. The high variability and the proximity to the tissue
      kallikrein gene render it suitable for application as a new tool in genetic
      studies for evaluation of the tissue kallikrein gene in the pathogenesis of human
      essential hypertension.

PMID- 9187665
TI  - Interstitial telomeric sequences at the junction site of a jumping translocation.
AB  - The mechanism(s) for the origin of jumping translocations (JTs) are unknown. To
      assess the possible involvement of telomeric sequences in the jumping process,
      metaphases of a patient with hydrops fetalis having a JT were analyzed for the
      presence of interstitial telomeres. Telomere DNA sequences were detected at the
      junction sites of the donor and the recipient chromosomes. Interstitial telomeric
      sequences have so far only been detected in JTs involving chromosome 15q in
      patients with Prader-Willi syndrome. Our finding of interstitial telomeric
      sequences in a JT with a chromosome different from chromosome arm 15q in a
      patient without Prader-Willi syndrome implies that telomere sequences may be
      common to all telomeric JTs. The possible role of telomeric sequences as a cause
      of the observed chromosomal mosaicism is discussed.

PMID- 9187666
TI  - alpha-satellite DNA methylation in normal individuals and in ICF patients:
      heterogeneous methylation of constitutive heterochromatin in adult and fetal
      tissues.
AB  - The methylation profile of ten alpha-satellites was investigated in normal
      individuals and in ICF (Immunodeficiency, Centromeric instability, Facial
      abnormalities) patients. Two out of three ICF patients showed modified
      methylation of these sequences, reproducing a placental profile. CENP-B boxes,
      the binding sites of centromeric protein B, were always skewed toward
      nonmethylation. Unexpected results were observed in normal individuals: in
      somatic adult tissues the methylation pattern of alpha-satellite DNA varied
      between chromosomes, and in fetal tissues these satellites were homogeneously
      undermethylated. Detailed methylation analysis of CENP-B boxes revealed that
      unmethylated alpha-satellite units coexist with thoroughly methylated regions.
      These observations showed that the two major components of constitutive
      heterochromatin are differently methylated in normal somatic and fetal tissues,
      since classical satellites are consistently methylated. The definite changes in
      the methylation profile of heterochromatin in somatic chromosomes and the
      asynchronous timing of methylation of classical and alpha-satellites during
      development may reflect specific roles of highly repeated sequences in genomic
      organization.

PMID- 9187667
TI  - Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish
      ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with
      liability to pressure palsies.
AB  - Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to
      pressure palsies (HNPP) are two inherited peripheral neuropathies. The most
      prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion,
      respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in
      the coding region of the myelin genes, peripheral myelin protein 22 (PMP22),
      myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT
      patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Dejerine-Sottas
      neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families
      lacking a deletion. We have investigated point and small mutations in the MPZ,
      PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients
      without duplications, and 5 HNPP patients without deletions. We found 15
      different mutations in 16 CMT patients (34%). Nine different mutations in ten
      patients were detected in the Cx32 gene, this being the most frequently involved
      gene in this series, whereas five mutations involved the MPZ gene and only one
      the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene
      involved two codons encoding arginine at positions 164 and 183, suggesting that
      these two codons may constitute two Cx32 regions prone to mutate in the Spanish
      population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1
      of the PMP22 gene in a family with autosomal dominance, which confirms allelic
      heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this
      mutation might behave as a null allele.

PMID- 9187669
TI  - Chromosome segregation in a man heterozygous for a pericentric inversion,
      inv(9)(p11q13), analyzed by using sperm karyotyping and two-color fluorescence in
      situ hybridization on sperm nuclei.
AB  - Analysis of sperm karyotypes and two-color fluorescent in situ hybridization
      (FISH) on sperm nuclei were carried out in a man heterozygous for the pericentric
      inversion inv(9)(p11q13). Sperm chromosome complements were obtained after in
      vitro fusion of zona-free hamster oocytes and donor sperm. A total of 314 sperm
      complements was analyzed: 153 (48.7%) carried the inverted chromosome 9 and 161
      (51.3%) carried the normal one. None of the sperm complements contained a
      recombinant chromosome 9, suggesting that no chiasmata were formed in the
      heterochromatic region. The frequency of structural chromosome aberrations
      unrelated to the inversion (8.3%) and the frequency of conservative aneuploidy
      (3.2%) were within the limits observed in our control donors. The proportions of
      X-bearing (47.3%) and Y-bearing sperm (52.7%) were not significantly different
      from the expected 1:1 ratio. The percentage of disomy for chromosome 21 was
      analyzed by two-color FISH in 10336 sperm nuclei. The disomy rate for chromosome
      21 (0.30%) was not significantly different from that found in our controls. These
      results suggest that the risk for this man of producing chromosomally abnormal
      offspring or spontaneous abortions was not increased, and do not support the
      existence of an interchromosomal effect for chromosome 21.

PMID- 9187668
TI  - Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in
      normal preimplantation embryos from fertile patients.
AB  - We have used multicolour fluorescent in situ hybridisation (FISH) with DNA probes
      for chromosomes X, Y and l to analyse spare untransferred cleavage-stage embryos
      after preimplantation diagnosis to avoid X-linked disease. In total, 93
      morphologically normal embryos were available from seven patients (six of proven
      fertility) who had undergone fourteen in vitro fertilisation (IVF) cycles. The
      chromosome patterns observed were classified into four groups; normal, abnormal
      (non-mosaic), mosaic and chaotic (uncontrolled division). Approximately half of
      the embryos were normal for the chromosomes tested. Two embryos only were
      aneuploid (non-mosaic) throughout but, after excluding those showing chaotic
      division, 30% were considered to be chromosomal mosaics. Of these, a minority had
      arisen because of mitotic non-disjunction or chromosome loss or gain, whereas the
      majority were ploidy mosaics, with haploidy being the most common. The occurrence
      of chaotically dividing embryos was strongly patient-related, i.e. some patients
      had 'chaotic' embryos in repeated cycles, whereas other patients were completely
      free of this type of anomaly. 'Chaotic' embryos are unlikely to progress beyond
      implantation. These findings have important implications both for routine IVF and
      preimplantation genetic diagnosis.

PMID- 9187670
TI  - Ataxic gait and mental retardation with absence of the paternal chromosome 8 and
      an idic(8)(p23.3): imprinting effect or nullisomy for distal 8p genes?
AB  - A female child with mild dysmorphisms, motor and mental retardation had a 45,XX,
      8,-8,+psu dic(8)(p23.3) karyotype in blood lymphocytes, skin fibroblasts and in a
      lymphoblastoid cell line. DNA analysis showed that the proposita was nullisomic
      for the 8pter region distal to D8S264, at less than 1 cM from the telomere.
      Analysis of DNA polymorphisms of 38 loci spread along the entire chromosome 8
      revealed that only maternal alleles were present, distributed in four
      heterozygous and four homozygous regions. This finding indicated that the
      rearrangement occurred during maternal meiosis in a chromosome recombinant with a
      minimum of seven crossovers. To our knowledge this is the first case of
      uniparental maternal disomy for chromosome 8 and of nullisomy for the distal 1-cM
      portion of the short arm. The available data are in favour of the assumption that
      no imprinted genes are present on chromosome 8. Thus, dysmorphisms, motor and
      mental retardation of the proposita are likely to be caused by the nullisomy for
      the region distal to D8S264, a region in which a recessive gene for epilepsy with
      progressive mental retardation is known to be located.

PMID- 9187671
TI  - Analysis of amino-acid and nucleotide variants in the spinocerebellar ataxia type
      1 (SCA1) gene in schizophrenic patients.
AB  - Several loci-containing genes that might harbour mutations predisposing to
      schizophrenia have recently been identified. The locus on chromosome 6p has been
      detected by several groups and appears to predispose to schizophrenia in 15%-30%
      of the pedigrees in one of these studies. The chromosome 6p locus for
      schizophrenia spans about 30 cM, between markers D6S296 and D6S276. The current
      transcription map of the 6p22-24 region includes three expressed sequence tags
      and six genes, one of which is the spinocerebellar ataxia type 1 (SCA1) gene.
      Patients with SCA1 have the CAG repeat sequence, which encodes a polyglutamine
      stretch in the ataxin-1 protein, expanded beyond the normal range. More recently,
      linkage disequilibrium between schizophrenia and the SCA1 CAG repeat has been
      reported. SCA1 is a good candidate gene for the schizophrenia-susceptibility
      locus on chromosome 6p as indicated by its expression pattern. We have studied
      the coding region of the SCA1 gene (exons 8 and 9) in samples from schizophrenia
      patients and have identified two amino-acid variants (S186C and P754S) and three
      nucleotide polymorphisms (1409A/G, 1865T/C and 2150A/G). One of the amino-acid
      changes (S186C) was present in two schizophrenic brothers from one family and in
      a schizophrenic patient and a non-affected subject of a second family but it was
      not detected in 100 unrelated subjects from the general population. S186C and
      other variants may be of relevance to the complex genetic factors involved in
      schizophrenia phenotypes.

PMID- 9187672
TI  - Fine mapping of the MLK-3 gene within 11q13 and its exclusion as the MEN1
      susceptibility gene.
AB  - MLK-3 kinase is a widely expressed serine/ threonine kinase that bears multiple
      protein interaction domains and regulates signals mediated by the stress
      responsive pathway. Thus, MLK-3 signaling affects numerous cellular processes,
      raising the possibility that MLK-3 might play a role in oncogenesis. In this
      report, we describe the fine mapping of the MLK-3 gene within the 11q13.1
      chromosomal region. By integrating data from somatic cell hybrids and double
      color fluorescence in situ hybridization on metaphase chromosomes and DNA fibers.
      MLK-3 has been assigned approximately 1 Mb telomeric of PYGM, close to the
      D11S546 locus. Since the MEN1 susceptibility locus is also located within the
      11q13.1 region, we have carried out Southern and Northern blot analyses, as well
      as protein truncation assays to establish whether abnormalities in MLK-3 lead to
      the development of this familial cancer syndrome. Our observations exclude MLK-3
      as the MEN1 gene.

PMID- 9187673
TI  - A second family with XLRH displays the mutation S244L in the CLCN5 gene.
AB  - Mutations in the CLCN5 gene, mapped in Xp11.22, have been recently reported to be
      associated with X-linked nephrolithiasis, X-linked recessive hypophosphataemic
      rickets and Dent's disease. We report a missense mutation in exon 6 of the CLCN5
      gene. The mutation in this pedigree is S244L, the same mutation as has previously
      been described in an Italian family showing a similar pathology. However, in the
      family reported here, affected males have developed neither nephrolithiasis nor
      nephrocalcinosis. The question arises whether we are dealing with a milder
      phenotype or whether a more severe pathology will develop with ageing.

PMID- 9187675
TI  - The identification of a (CGG)6AGG insertion within the CGG repeat of the FMR1
      gene in Asians.
AB  - We have evaluated the structure of the CGG repeat within the FMR1 gene of an
      Asian population and found the most common size of the repeat to be 29 and 30
      with a minor population of 36 repeats. We have isolated and sequenced DNA
      containing the 36 repeats and found the basis sequence to be (CGG)9AGG(CGG)9AGG
      (CGG)6AGG(CGG)9; with a (CGG)6)AGG insertion, designated as 9A9A6A9. Of 144 Asian
      chromosomes, 11 (8%) had sequences with this insertion. Six different variations
      of the basic sequence were observed in the population: 9A9A6A2A9, 9A9A6A11,
      9A9A16, 9A9A15, 8A9A6A6A9, and 11A6A6A9. All but one of the chromosomes with the
      insertion had the haplotype of DXS548/ FRAXAC1: 194/D suggesting that the
      sequences with the 6A insertion arose from a single ancestral allele. We have not
      observed the insertion in the FMR1 gene of Caucasians or Native Americans. The
      (CGG)6AGG insertion may be unique to Asians.

PMID- 9187674
TI  - Biochemical and genetic studies of four patients with pyruvate dehydrogenase E1
      alpha deficiency.
AB  - We report studies of four patients with pyruvate dehydrogenase complex (PDH)
      deficiency caused by mutations in the E1 alpha subunit. Two unrelated male
      patients presented with Leigh syndrome and a R263G missense mutation in exon 8.
      This mutation has previously been described in males with the same phenotype. The
      two other patients had different novel mutations: (1) an 8-bp deletion at the C
      terminus (exon 11) was found in one allele of a young girl suffering from
      microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only
      presented with motor neuropathy. These mutations were not found in the mothers of
      any of the four cases. Immunoblot analysis revealed decreased immunoreactivity
      for the E1 alpha and E1 beta subunits in three out of the four patients. These
      findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2)
      the R263G mutation is more frequent in male cases than are other mutations and
      this amino acid is a hot spot for gene mutations, (3) the last eight amino acids
      may be important for the conformation of the tetrameric E1-PDH enzyme, and (4)
      the amino acids at positions 88, 263 and 382-387 are essential for the linking of
      the alpha subunit with the beta subunit and for the activity of the holoenzyme.

PMID- 9187676
TI  - Simultaneous detection of size and sequence polymorphisms in the transcribed
      trinucleotide repeat D2S196E (EST00493).
AB  - Long expansions of transcribed trinucleotide microsatellites have been
      etiologically associated with some neurological diseases. The investigation of
      such novel polymorphisms has thus become a subject of great interest. We searched
      the expressed sequence tag databank for reiterated trinucleotides and selected
      EST00493 (D2S196E) with 14 tandem ACA triplets as a potentially polymorphic
      locus. Size variation was readily detected, with four common alleles containing
      12-15 repeats. In addition, we observed distinct heteroduplexes in amplifications
      from individuals with identical ACA genotypes. Sequencing of their polymerase
      chain reaction (PCR) products revealed a G-->A transition immediately preceding
      the trinucleotide repeats, hence defining 8 distinct haplotypes and 36 possible
      genotypes. Indeed, mutation detection enhancement gel electrophoresis of mixed
      PCR products from cloned haplotypes revealed 24 distinct heteroduplex patterns
      for the six possible trinucleotide heterozygotes. The observation of heteroduplex
      patterns in non-denaturing polyacrylamide gel electrophoresis (instead of the
      more commonly used denaturing gels) can thus be utilized to increase the
      informativeness of microsatellite polymorphisms by unraveling otherwise cryptic
      sequence variation. The D2S196E polymorphism has proved useful for demonstrating
      microsatellite instability and loss of heterozygosity in colorectal tumors.

PMID- 9187677
TI  - HLA-DRA promoter polymorphism and diversity generation within the immune system.
AB  - Multiple major histocompatibility complex (MHC) alleles exist at most class I and
      II loci. Polymorphism of MHC polypeptides may reflect either different levels of
      selective pressure operating on each molecule or different mutation rates at
      different loci. To gain further insight into this issue, we sequenced the non
      coding promoter region of the HLA-DRA gene from several Epstein-Barr virus
      transformed B cell lines and compared the extent of polymorphism found in this
      region with the known polymorphism of the HLA-DQB promoter. Our results indicate
      that the HLA-DRA promoter displays a low level of polymorphism while the promoter
      of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of
      DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to
      have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken
      together, these results suggest that the HLA-DRA promoter is highly conserved and
      may be under a stronger functional constraint than the promoter regions of other
      MHC class II genes.

PMID- 9187678
TI  - Recombination in a balanced complex translocation of a mother leading to a
      balanced reciprocal translocation in the child. Review of 60 cases of balanced
      complex translocations.
AB  - We report an unusual case of a balanced reciprocal translocation with a
      recombinant chromosome which has arisen from a familial balanced complex
      translocation. Fluorescence in situ hybridization studies were essential for the
      identification of the breakpoints. A review of 60 cases of balanced complex
      translocations (BCT) has revealed three cases similar to ours. Carriers of BCT
      have a high risk of having spontaneous abortions or a child with an unbalanced
      karyotype. Certain types of balanced rearrangements involving an insertion can
      give rise to a simpler balanced translocation as a result of crossover. Our
      observations support the assumption that the chance that a de novo balanced
      complex translocation is associated with an abnormal phenotype increases with the
      number of breakpoints.

PMID- 9187679
TI  - Molecular analysis of Gaucher disease: distribution of eight mutations and the
      complete gene deletion in 27 patients from Germany.
AB  - Gaucher disease is the most common lysosomal storage disease with a high
      prevalence in the Ashkenazi Jewish population but it is also present in other
      populations. The presence of eight mutations (1226G, 1448C, IVS2+1. 84GG, 1504T,
      1604T, 1342C and 1297T) and the complete deletion of the beta-glucocerebrosidase
      gene was investigated in 25 unrelated non-Jewish patients with Gaucher's disease
      in Germany. In the Jewish population, three of these mutations account for more
      than 90% of all mutated alleles. In addition, relatives of two patients were
      included in our study. Restriction fragment length polymorphism analysis and
      sequencing of PCR products obtained from DNA of peripheral blood leukocytes was
      performed for mutation analysis. Gene deletion was detected by comparison of
      radioactively labelled PCR fragments of both the functional beta
      glucocerebrosidase gene and the pseudogene. Among the unrelated patients, 50
      alleles were investigated and the mutations identified in 35 alleles (70%),
      whereas 15 alleles (30%) remained unidentified. The most prevalent mutation in
      our group of patients was the 1226G (370Asn-->Ser) mutation, accounting for 18
      alleles (36%), followed by the 1448C (444Lcu-->Pro) mutation, that was found in
      12 alleles (24%). A complete gene deletion was present in two alleles (4%). The
      IVS1+2 (splicing mutation), the 1504T (463Arg-->Cys) as well as the 1342C (409Asp
      ->His) mutations were each present in one allele (2%). None of the alleles
      carried the 84GG (frame-shift), 1604A (496Arg-->His) or the 1297T (394Val-->Leu)
      mutation. This distribution is different from the Ashkenazi Jewish population but
      is similar to other Caucasian groups like the Spanish and Portuguese populations.
      Our results confirm the variability of mutation patterns in Gaucher patients of
      different ethnic origin. All patients were divided into nine groups according to
      their genotype and their clinical status was related to the individual genotype.
      Genotype/phenotype characteristics of the 1226G, 1448C, and 1342C mutations of
      previous studies were confirmed by our results.

PMID- 9187680
TI  - Peculiarities of the GSTM1 0/0 genotype in French heavy smokers with various
      types of chronic bronchitis.
AB  - A homozygous gene deletion of the glutathione S-transferase M1 (GSTM1) locus of
      genomic DNA from blood spots was studied by the polymerase chain reaction in a
      group of French heavy smokers (n = 361), which included patients with severe
      chronic bronchitis (SCB; n = 87), moderate chronic bronchitis (MCB: n = 102) and
      hard smokers (HS) with no permanent clinical symptoms of chronic bronchitis (n =
      172). The GSTM1 0/0 genotype was found in 71.3% and 65.7% of cases in SCB and
      MCB, respectively, compared with only 47.1% in the control HS group (P = 0.0002).
      This latter figure (47.1%) is consistent with the average GSTM1 deletion
      frequency in French Caucasians. Moreover, the results showed a significant
      difference in the distribution of the GSTM1 0/0 genotype for both the SCB and MCB
      groups against the control HS group, according to gender (SCB: P = 0.001; MCB: P
      = 0.005), age (SCB: P = 0.0001; MCB: P = 0.005) and smoking history (SCB: P =
      0.0001; MCB: P = 0.005). Thus, individuals homozygous for the GSTM1 gene
      deletion, especially in the under-41 age group (SCB: P = 0.001; MSB: P = 0.04)
      with an average smoking history of 16-30 pack-years (SCB: P = 0.002; MSB: P =
      0.01) are more prone to chronic lung diseases, such as SCB and MCB, than are
      GSTM1 +/+ or 0/+ subjects. Population screening of young people for the
      identification of GSTM1 0/0 subjects, with special emphasis on smoking habits,
      might be useful (1) for the early detection of individuals at high risk of lung
      complications caused by environmental toxins and pollutants and (2) in clinical
      practice, in order to prevent the development of chronic bronchitis, which is a
      common disease.

PMID- 9187681
TI  - Putative association of a mutant ROM1 allele with retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous form of
      retinal degeneration. Several genes and loci have been shown to be involved in
      the disease, although each of them only accounts for a few cases. Mutations in
      the gene encoding ROM1, a rod-specific protein, have been putatively associated
      with several forms of RP. Here we describe a double-mutant allele of this gene,
      P60T and T108M, present in two affected sibs and also in two healthy members of a
      Spanish RP family. The same double-mutant allele was previously considered to be
      responsible for autosomal dominant RP in one family. We now report data that
      question the potential pathogenicity of these two ROM1 mutations.

PMID- 9187682
TI  - Physical mapping of the HOXA1 gene and the hnRPA2B1 gene in a YAC contig from
      human chromosome 7p14-p15.
AB  - A cluster of homeobox-containing genes (HOXA) and a heterogeneous nuclear
      ribonucleoprotein (hnRPA2B1) have both previously been assigned to chromosome
      7p15 by in situ hybridization. In this report, we constructed a YAC contig from
      chromosome 7p14-p15, between markers D7S2496 and D7S1838, and determined the
      position of the HOXA1 gene and the hnRPA2B1 gene in this YAC contig.

PMID- 9187683
TI  - Differential stability of the (GAA)n tract in the Friedreich ataxia (STM7) gene.
AB  - Friedreich ataxia (FA) is an autosomal recessive, neurodegenerative disorder
      characterized by polypurine trinucleotide expansion. The (GAA)n motif is located
      in intron 18 of the STM7 gene (previously considered as intron 1 of the X25 gene)
      on chromosome 9q13. We studied the distribution profile of the polymorphic (GAA)n
      repetitive tract in 178 healthy individuals. The number of repeats of the
      trinucleotide block ranged from 7 to 29. In three individuals there were more
      than 29 repetitions of the GAA motif. While two of the individuals would be
      diagnosed as carriers of the FA mutation (GAA size > 90), the status of the third
      person, with a (GAA)58 tract, appears less clear at present. Thus an FA carrier
      rate of 1/60 to 1/90 can be assumed for the German population. In addition an
      intermediate-sized allele, (GAA)38 was identified in a mother with two affected
      children. The (GAA)38 allele appears to be expanded during transmission to at
      least (GAA)66 and (GAA) > 400 in her two FA-affected offspring. Therefore the
      shortest known STM7 allele conferring FA is (GAA)66. These novel facts have to be
      considered for differential diagnosis and definition of the FA carrier state.

PMID- 9187684
TI  - A review of clinical and pathological prostatitis syndromes.

PMID- 9187685
TI  - The international index of erectile function (IIEF): a multidimensional scale for
      assessment of erectile dysfunction.
AB  - OBJECTIVES: To develop a brief, reliable, self-administered measure of erectile
      function that is cross-culturally valid and psychometrically sound, with the
      sensitivity and specificity for detecting treatment-related changes in patients
      with erectile dysfunction. METHODS: Relevant domains of sexual function across
      various cultures were identified via a literature search of existing
      questionnaires and interviews of male patients with erectile dysfunction and of
      their partners. An initial questionnaire was administered to patients with
      erectile dysfunction, with results reviewed by an international panel of experts.
      Following linguistic validation in 10 languages, the final 15-item questionnaire,
      the international index of Erectile Function (IIEF), was examined for
      sensitivity, specificity, reliability (internal consistency and test-retest
      repeatability), and construct (concurrent, convergent, and discriminant)
      validity. RESULTS: A principal components analysis identified five factors (that
      is, erectile function, orgasmic function, sexual desire, intercourse
      satisfaction, and overall satisfaction) with eigenvalues greater than 1.0. A high
      degree of internal consistency was observed for each of the five domains and for
      the total scale (Cronbach's alpha values of 0.73 and higher and 0.91 and higher,
      respectively) in the populations studied. Test-retest repeatability correlation
      coefficients for the five domain scores were highly significant. The IIEF
      demonstrated adequate construct validity, and all five domains showed a high
      degree of sensitivity and specificity to the effects of treatment. Significant (P
      values = 0.0001) changes between baseline and post-treatment scores were observed
      across all five domains in the treatment responder cohort, but not in the
      treatment nonresponder cohort. CONCLUSIONS: The IIEF addresses the relevant
      domains of male sexual function (that is, erectile function, orgasmic function,
      sexual desire, intercourse satisfaction, and overall satisfaction), is
      psychometrically sound, and has been linguistically validated in 10 languages.
      This questionnaire is readily self-administered in research or clinical settings.
      The IIEF demonstrates the sensitivity and specificity for detecting treatment
      related changes in patients with erectile dysfunction.

PMID- 9187686
TI  - Conservative management of colon injury following percutaneous renal surgery.
AB  - OBJECTIVES: Colon injury during percutaneous renal surgery is rare and can result
      in significant morbidity. Our objective was threefold: (1) to identify risk
      factors for colon injuries; (2) to optimize prevention of such injuries; and (3)
      to devise a treatment strategy for optimal management of such colon injuries.
      METHODS: Between July 1990 and July 1995, all percutaneous renal procedures
      performed at three kidney stone centers were reviewed (Kaiser Permanente Medical
      Center, Los Angeles; Hospital of the Good Samaritan, Los Angeles; and University
      of California at San Francisco). In addition, a review of the pertinent
      literature was performed. RESULTS: Five patients who suffered colon injuries
      during percutaneous renal surgery were identified. All had undergone percutaneous
      nephrolithotomy, and all injuries were extraperitoneal. Mean age was 31 years
      (range 17 to 52). Three patients were considered lean, and the other two were of
      average body habitus. Four of 5 patients were male. Three injuries occurred on
      the left side and two on the right. Recognition of colon injury occurred
      postoperatively in 4 patients and intraoperatively in 1 patient. Presenting signs
      and symptoms included fever, fecaluria, abdominal pain, and leukocytosis.
      CONCLUSIONS: High risk patients for colon injuries are young, lean males with
      minimal retroperitoneal fat, in whom a retrorenal colon is more likely. High risk
      patients should be accessed with a more superior and medial puncture.
      Retroperitoneal colon injuries can be successfully managed conservatively with
      early recognition and appropriate drainage of the urinary and intestinal tracts.
      A treatment algorithm is presented.

PMID- 9187687
TI  - Decreased use of post-renal transplant imaging.
AB  - OBJECTIVES: The current need to evaluate necessity and cost of diagnostic and
      therapeutic procedures extends to transplant services. We reviewed our experience
      over the past 3 years as we have moved away from routine post-transplant nuclear
      medicine scans, ultrasounds, and cystograms. METHODS: From January 1, 1992 to
      December 31, 1994, 252 kidney transplants were performed at Virginia Mason
      Medical Center. There were 74 live donor and 178 cadaver donor kidneys
      transplanted. The records of these patients were reviewed for the type and number
      of post-transplant imaging done during their initial hospitalization. RESULTS:
      During the study period, the number of post-transplant imaging studies per
      patient decreased from 2.7 to 1.4 (P = 0.000), the percentage of patients
      discharged without any studies rose from 2.8% to 24.4% (P = 0.001), and the trend
      in 1-year actual graft survival increased from 84.7% to 93.0% (P = 0.187).
      CONCLUSIONS: Post-transplant imaging studies can be safely reduced. Many patients
      with good initial graft function can avoid having any studies.

PMID- 9187688
TI  - Finasteride significantly reduces acute urinary retention and need for surgery in
      patients with symptomatic benign prostatic hyperplasia.
AB  - OBJECTIVES: A pooled analysis of all available randomized trials with 2-year
      follow-up data with finasteride and placebo was undertaken to further investigate
      recent observations that finasteride use may reduce the occurrence of acute
      urinary retention (AUR) and benign prostatic hyperplasia (BPH)-related surgical
      intervention. METHODS: Occurrences of AUR and surgical intervention were examined
      by treatment group in a pooled series of 4222 men with moderately symptomatic
      BPH. RESULTS: In total, 81 occurrences of AUR were reported, 24 (1.1%) of 2113 in
      the finasteride group and 57 (2.7%) of 2109 in the placebo group. The hazard
      ratio was consistent in all three studies, with a 57% decrease in the hazard rate
      for occurrence of AUR with finasteride compared with that for placebo present in
      the pooled data set over the 2-year study period (P < 0.001). Additionally, 227
      surgical interventions were recorded over the 2-year study period, 89 (4.2%) of
      2113 in the finasteride group and 138 (6.5%) of 2109 in the placebo group. The
      hazard ratio was consistent across the three studies, with a 34% reduction in the
      hazard rate for occurrence of surgery with finasteride compared with that for
      placebo (P < 0.002). Overall, there was 35% reduction in the two BPH-related end
      points (ie, AUR or surgery). CONCLUSIONS: Treatment with finasteride for up to 2
      years more than halves the frequency of AUR and reduces surgical intervention by
      over one third relative to placebo in patients with moderate BPH. This is the
      first demonstration that long-term medical therapy can reduce clinically
      significant end points such as AUR or surgery, and these data have important
      implications for the long-term management of patients with BPH.

PMID- 9187689
TI  - Transurethral needle ablation (TUNA) of the prostate: a clinical and urodynamic
      evaluation.
AB  - OBJECTIVES: This prospective study evaluated the clinical and urodynamic changes
      in patients with obstruction due to benign prostatic hyperplasia (BPH) treated
      with transurethral needle ablation (TUNA). METHODS: One hundred twenty patients
      with obstructive uropathy due to BPH were treated with the TUNA procedure between
      January 1994 and December 1995. All patients were selected according to the
      criteria established by the guidelines proposed by the International Consensus
      Committee (World Health Organization, Paris, 1993). The TUNA procedure was
      performed in an outpatient setting using topical intraurethral anesthesia (2%
      lidocaine gel). RESULTS: Patients showed a decrease in irritative symptoms as
      measured by the international Prostate Symptom Score (IPSS) and postprocedure
      urodynamic parameters. The mean (+/- SD) pretreatment IPSS was 20.8 +/- 4.5. At 3
      months, the IPSS decreased to 9.7 +/- 3.0 (108 patients) (P < 0.001). At 6 months
      it decreased to 6.8 +/- 3.1 (86 patients) and remained at 6.2 +/- 2.9 (72
      patients) and 6.7 +/- 3.8 (42 patients) at 12 and 18 months, respectively (P <
      0.001). At 1 year after treatment, the peak flow rate (Qmax) increased from 8.2
      +/- 3.4 mL/s to 15.9 +/- 2.1 mL/s and was 14.1 +/- 2.5 mL/s at 18 months of
      follow-up (P < 0.01). Urodynamic re-evaluation performed in 72 patients 12 months
      after TUNA demonstrated the absence of obstruction in 30 (41.7%). An additional
      30 patients (41.7%) had equivocal results, whereas the remaining 12 (16.6%) still
      had obstruction, according to the Abrams-Griffith nomogram. Mean detrusor
      pressure at Qmax decreased from 85.3 +/- 18.5 cm H2O to 63.7 +/- 24.9 cm H2O at
      12 months of follow-up. CONCLUSIONS: Our results confirm that the TUNA procedure
      is safe and effective when performed as an outpatient procedure. In addition,
      TUNA produced better results in patients presenting with moderate to severe
      irritative symptoms and minimal obstruction as determined by pressure/flow
      studies.

PMID- 9187690
TI  - Quantitative assessment of variables that influence soft-tissue
      electrovaporization in a fluid environment.
AB  - OBJECTIVES: To evaluate the process of soft-tissue electrovaporization and to
      study variables that affect tissue clearance rates in a laboratory setting, in
      order to identify parameters that can optimize transurethral electrovaporization
      of the prostate. METHODS: Fresh bovine skeletal muscle, equivalent in impedance
      and surface properties to the human prostate, was submerged in 3.3% sorbitol
      solution and electrovaporized with a grooved monopolar electrode attached to the
      weighted arm of a linear actuator. The effects of excursion rate, applied
      mechanical load, power setting, electrode configuration, and generator
      performance on the volume of tissue removed, were assessed. RESULTS: Tissue
      removal increased significantly when electrode excursion rate was slowed from 25
      to 15 mm/s (P < 0.05) and then to 10 mm/s (P < 0.05); when the load was increased
      from 20 to 50 g (P < 0.005); and when dial power was increased from 120 to 150 W
      (P < 0.01). Tissue removal was generator dependent. There was no significant
      difference between the Force 40 and the Force 2 (P > 0.4), but a new computer
      controlled constant power output generator (Force FX) did significantly improve
      tissue vaporization at an equivalent power setting (P < 0.005 and P < 0.01,
      respectively). Tissue removal was also dependent upon electrode configuration,
      with the VaporTrode-Grooved Bar removing significantly more tissue than either an
      ungrooved roller bar of equivalent size or 2-mm smooth roller ball, respectively,
      both after a single pass (P < 0.001 and P < 0.05) and after five repeated passes
      (P < 0.05 and P < 0.005). The histologic depth of tissue thermal effect was less
      than 1 mm, but it was 38% greater for the VaporTrode-Grooved Bar (0.68 mm) than
      for the standard cutting loop (0.5 mm, P < 0.01). CONCLUSIONS: Using a novel
      method to quantify tissue removal, we have demonstrated that electrode
      configuration, excursion rate, applied load, power setting, and generator
      performance are interdependent factors that influence the efficacy of the
      electrovaporization process in a fluid environment.

PMID- 9187691
TI  - Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial
      neoplasia and adenocarcinoma: a novel prostate cancer marker.
AB  - OBJECTIVES: We describe the expression of a potentially new tumor marker, human
      glandular kallikrein 2 (hK2), that may be useful as an adjunct to prostate
      specific antigen (PSA) in the diagnosis and monitoring of prostate cancer.
      METHODS: We evaluated 257 radical prostatectomy specimens removed at the Mayo
      Clinic with pathologic Stage 12 adenocarcinoma to compare the cytoplasmic
      expression of hK2, PSA, and prostatic acid phosphatase (PAP) in benign tissue,
      high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. Two
      monoclonal antibodies, hK2-A523 and hK2-G586, specific for hK2 were used, as well
      as antibodies against PSA (PSM-773) and PAP (polyclonal). RESULTS: Intense
      epithelial cytoplasmic immunoreactivity was observed in every case for hK2-A523,
      hK2-G586, PSA, and PAP (100% of cases, respectively). The intensity and extent of
      hK2 expression for both antibodies were greater in cancer than high-grade PIN;
      furthermore, high-grade PIN was greater than benign epithelium. Cases of Gleason
      primary grade 4 and 5 cancer showed hK2 staining in almost every cell, whereas
      there was greater heterogeneity of staining in lower grades of cancer. In marked
      contrast to hK2, PSA and PAP immunoreactivity was most intense in benign
      epithelium and stained to a lesser extent in PIN and carcinoma. The number of
      immunoreactive cells for hK2 and PSA was not predictive of cancer recurrence.
      CONCLUSIONS: hK2 was expressed in every cancer, and the expression incrementally
      increased from benign epithelium to high-grade PIN and adenocarcinoma. PSA and
      PAP displayed inverse immunoreactivity compared with hK2. The expression of hK2
      and PSA was not predictive of cancer recurrence in patients with Stage T2
      carcinoma. Expression of hK2 indicates that this kallikrein antigen is both
      prostate localized and tumor associated. Tissue expression of hK2 appears to be
      regulated independently of PSA and PAP. Further studies are needed to determine
      whether tissue immunoreactivity of hK2 will prove clinically useful in the
      diagnosis and monitoring of prostate cancer.

PMID- 9187692
TI  - Predictive accuracy of transrectal ultrasound-guided prostate biopsy:
      correlations to matched prostatectomy specimens.
AB  - OBJECTIVES: To characterize observed differences in Gleason score between
      prostate biopsy and corresponding radical retropubic prostatectomy (RRP)
      specimens. METHODS: One hundred consecutive clinically localized prostate cancers
      diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and treated with RRP
      were reviewed. All specimens were evaluated in blinded review by a single expert
      uropathologist and contrasted with the initial histologic analysis, performed by
      multiple pathologists. RESULTS: Mean Gleason score of TRUS-Bx specimens for
      blinded review and at initial evaluation were 6.6 +/- 0.1 and 6.0 +/- 0.1 (P <
      0.001). Corresponding RRP values were 6.8 +/- 0.1 and 6.5 +/- 0.1 (P < 0.03).
      Differences in Gleason score between TRUS-Bx and RRP at initial evaluation were
      significant (P < 0.02), but not in blinded review (P = NS). In blinded review,
      TRUS-Bx correctly predicted RRP histology for 88% of men with lesions scored as
      Gleason 5 to 7 and 41% of men with well-(Gleason score of 2 to 4) or poorly
      differentiated (Gleason score of 8 to 10) lesions (P < 0.01). CONCLUSIONS: TRUS
      Bx does not accurately reflect RRP histology when predicting well- or poorly
      differentiated lesions. Prostate cancer treatment algorithms should not be
      predicated upon biopsy histology alone. Histologic interpretation is more
      accurate and precise when performed by a single experienced uropathologist.

PMID- 9187693
TI  - Diagnostic value of additional systematic prostate biopsies in patients
      undergoing transurethral resection of the prostate.
AB  - OBJECTIVES: There are patients with obstructive voiding symptoms and suspicious
      screening parameters in whom prostate cancer (PC) cannot be excluded prior to
      transurethral resection of the prostate (TURP). The goal of our study was to
      assess the diagnostic value of systematic biopsies of the peripheral zone of the
      prostate performed during TURP. METHODS: Between 1990 and 1995, 132 patients
      (average age 69.5 +/- 7.4 years) with at least one suspicious screening parameter
      underwent a TURP and additional systematic prostate biopsies. Pathology reports
      were reviewed to verify whether PC was present in the TURP chips or in the biopsy
      cores. RESULTS: Histologic examination found benign prostatic hyperplasia in 52,
      prostatitis in 53, and PC in 27 patients. PC was detected only with TURP in 11
      patients (40.8%). In 15 patients (55.6%), both TURP and prostate biopsies showed
      PC. There was only 1 patient (3.7%) with a positive biopsy in whom the
      examination of the resection chips did not detect PC. In patients with negative
      digital rectal examination and intermediate prostate-specific antigen levels,
      prostate-specific antigen density was not able to differentiate between benign
      and cancerous lesions. CONCLUSIONS: There seems to be a subgroup of patients
      where systematic and repeated prostate biopsies fail to detect PC prior to TURP.
      Although the increase in the detection rate through additional prostate biopsies
      of the peripheral zone is limited, we would recommend these biopsies in addition
      to TURP, especially if patients are eligible for further curative treatment
      options.

PMID- 9187694
TI  - Complications of transrectal ultrasound-guided systematic sextant biopsies of the
      prostate: evaluation of complication rates and risk factors within a population
      based screening program.
AB  - OBJECTIVES: Screening for prostate cancer to reduce the mortality and morbidity
      from this disease has become an important issue in recent years. Of all
      procedures used to diagnose prostate cancer, biopsy of the prostate is the cause
      of most complications. To evaluate the safety of the screening procedure, we have
      studied the complications and risk factors for complications within the screened
      population of the European Randomized Study of Screening for Prostate Cancer
      (ERSPC), Rotterdam section. METHODS: Between June 1994 and July 1996, 1687
      transrectal ultrasound-guided systematic sextant biopsies were performed after
      screening 6198 men through prostate-specific antigen level, digital rectal
      examination, and transrectal ultrasonography. RESULTS: From these 1687 biopsies,
      302 cases of prostate cancer were diagnosed. Mild complications such as hematuria
      and hematospermia were reported frequently with rates of 23.6% and 45.3%,
      respectively. More severe complications were far less frequently seen. Fever,
      usually of low grade, was seen after 4.2% of biopsies. Seven men (0.4%) were
      admitted to a hospital after biopsy. Risk factors for complications could not be
      identified. CONCLUSIONS: Review of the literature concerning transrectal biopsies
      of the prostate shows that the complication rates within this screened population
      are comparable to those reported within referred patients. The admittance rate is
      slightly lower. Transrectal ultrasound-guided systematic sextant biopsy of the
      prostate is a safe procedure for the diagnosis of prostate cancer within the
      general population; however, identification of risk factors for complications
      might further improve the safety of the screening procedure.

PMID- 9187695
TI  - Detection of intact prostate cancer cells in the blood of men with prostate
      cancer.
AB  - OBJECTIVES: To develop a procedure to be used to find, identify, and characterize
      the living prostate cancer cells in the blood of patients with prostate cancer.
      METHODS: The procedure is based on a negative selection approach that removes
      most of the blood cells and collects the remaining prostate cancer cells, which
      are identified and characterized by fluorescent in situ hybridization with
      deoxyribonucleic acid probes and by indirect fluorescent immunocytochemical
      staining. The blood cells are removed via density gradient centrifugation.
      RESULTS: Using the prostate cancer LNCaP cells as a model, the recovery rate of
      the added prostate cancer cells to 10 mL of blood was about 85%, with a dilution
      of 1 LNCaP cell to 10,000 white blood cells or more. Blood samples varying from 9
      to 27 mL were collected and analyzed from 8 men aged 54 to 79 years who had
      varying levels of PSA in serum. In one blood sample, prostate cancer cells were
      not found; in the seven other samples, the number of prostate cancer cells found
      per milliliter of blood varied from 1 to 20. Prostate cancer cells were not found
      in 7.5 to 15-mL blood samples from 3 healthy younger men. The prostate cells were
      found to be aneuploid for chromosomes 7 and 8, highly suggestive that these cells
      were cancerous. CONCLUSIONS: Using a negative selection approach, prostate cells
      can be found in the blood of patients with prostate cancer, as identified by
      prostate cell-specific probes and antibodies. These cells were found to be
      aneuploid.

PMID- 9187696
TI  - Prognostic significance of prostate-specific antigen in stage T1c prostate cancer
      treated by radical prostatectomy.
AB  - OBJECTIVES: Increasingly, nonpalpable prostate-specific antigen (PSA)-detected
      (Stage T1c) tumors are being treated with curative intent. Presently, only
      limited information is available regarding pathologic findings correlated with
      preoperative PSA levels. Herein, we report the characteristics of Stage T1c
      tumors in a contemporary surgical series. METHODS: Clinical and pathologic
      results in 107 patients with Stage T1c tumors treated with radical prostatectomy
      were compared with those in 300 patients with palpable (Stage T2) tumors.
      Multivariate analysis was performed to determine which clinical variables
      independently predicted pathologic staging. RESULTS: Stage T1c tumors were
      equivalent to Stage T2 tumors with respect to organ-confined and margin-positive
      rates. PSA level was the strongest independent predictor of extracapsular and
      margin-positive rates (P = 0.003). The absence of palpability was not a
      significant predictor of pathologic outcome. Significantly higher rates of organ-
      and specimen-confined disease were seen in patients with PSA levels less than
      10.0 ng/mL, particularly less than 7.0 ng/mL. Patients with serum PSA levels
      greater than 20 ng/mL were at high risk for positive margins (relative risk 5.42,
      P < 0.001). CONCLUSIONS: Stage T1c tumors represent a heterogeneous group of
      cancers. These tumors are pathologically similar to Stage T2 tumors, and patients
      should be offered similar treatment options. PSA level was the strongest
      predictor of pathologic stage, irrespective of tumor palpability. These results
      suggest that efforts directed toward identifying cancers, including nonpalpable
      tumors, in patients with early PSA elevations may result in improved rates of
      organ-confined disease. The impact of treatment on Stage T1c tumors remains to be
      defined.

PMID- 9187697
TI  - Comparison of four automated prostate-specific antigen assays for detection of
      recurrence after radical prostatectomy.
AB  - OBJECTIVES: To compare four assays-the Abbott IMx, the Tosoh, the Chiron ACS PSA,
      and the Chiron ACS PSA2-in their ability to detect prostate-specific antigen
      (PSA) after radical prostatectomy. METHODS: Serum samples were drawn on all men
      who had had a previous radical prostatectomy and who were seen in the urology
      clinic in March 1995. The results of each assay were compared using linear
      regression. RESULTS: Twenty-two patients had an undetectable PSA by the IMx
      assay. The PSA was over the residual cancer detection limit (RCDL) of the Tosoh
      assay in 5 of these patients. The PSA was over the RCDL of the ACS PSA assay in
      15 of these patients and over the RCDL of the PSA2 assay in 2 patients. There
      were no patients whose PSA was less than the RCDL of the ACS PSA assay who had a
      measurable PSA level by any of the other assays. CONCLUSIONS: There is a
      difference among PSA assays in their ability to detect low levels of PSA after
      radical prostatectomy. The ACS PSA assay is the most sensitive, and the IMx assay
      is the least sensitive.

PMID- 9187698
TI  - Patient satisfaction with short stays for radical prostatectomy.
AB  - OBJECTIVES: We evaluated the effects on patient satisfaction of shortened
      postoperative hospital stays after radical retropubic prostatectomy (RRP).
      METHODS: A previously validated, self-administered instrument was used to assess
      satisfaction with care in a retrospective, cross-sectional study of 129 men who
      had undergone RRP after implementation of a short-stay clinical care pathway.
      Health-related quality of life outcomes, comorbidity, and sociodemographic data
      were also measured with established instruments. RESULTS: Satisfaction with care
      was uniformly high and did not vary with length of stay (LOS), time since
      surgery, or health-related quality of life. CONCLUSIONS: Decreased LOS mandated
      by the need for a cost-efficiency path does not adversely affect patient
      satisfaction.

PMID- 9187699
TI  - Transurethral collagen injection for treatment of postprostatectomy urinary
      incontinence in men.
AB  - OBJECTIVES: Transurethral injection of glutaraldehyde cross-linked bovine
      collagen has recently been advocated as a potentially useful treatment modality
      for management of urinary incontinence. The reported clinical experience with
      urethral collagen injection in adult males has been limited. METHODS: This study
      summarizes the current literature and reviews the clinical results of collagen
      injection in a group of 25 men with incontinence after either transurethral or
      radical prostatectomy. RESULTS: The overall results in this series were
      disappointing. Only 2 patients (8%) achieved significant improvement with this
      treatment. Eight patients (32%) experienced minimal improvement in symptoms, and
      15 (60%) remained incontinent with no improvement in symptoms after collagen
      injection. The number of injection procedures and volume of collagen material
      implanted did not correlate with clinical outcome. Five patients (20%) have
      subsequently required placement of an artificial urinary sphincter to control
      their incontinence. CONCLUSIONS: We conclude that transurethral injection of
      glutaraldehyde cross-linked bovine collagen has a limited role in the management
      of urinary incontinence in adult men after prostatectomy.

PMID- 9187701
TI  - Reactive oxygen species generation by seminal cells during cryopreservation.
AB  - OBJECTIVES: To test the hypothesis that conventionally used procedures for semen
      cryopreservation may cause an increase in the production of reactive oxygen
      species (ROS) by sperm or by seminal leukocytes, which may contribute to poor
      sperm function following cryopreservation. METHODS: Eighteen semen specimens with
      normal parameters from healthy male donors 22 to 40 years of age were each
      divided into two portions. The first portion was combined 1:1 with Test Yolk
      Buffer-Glycerol Freezing Medium and was frozen by gradual cooling into liquid
      nitrogen (-196 degrees C). The second portion was washed and the cells were
      resuspended in Sperm Washing Medium (SWM) and incubated at room temperature to
      serve as controls. After a period of treatment, frozen samples were thawed and
      semen cells were washed and resuspended in SWM. ROS generation by semen cells
      from each treatment group was measured on a luminometer. Sperm motility, sperm
      viability, and sperm membrane integrity were also measured in both control and
      freeze-thaw samples. To further assess ROS generation by semen cells during the
      cooling process, aliquots of washed semen cells and purified polymorphonuclear
      leukocytes (PMNs) were incubated separately at different temperature conditions
      (37 degrees C, 22 degrees C, 4 degrees C, and -20 degrees C). ROS activity in
      each treatment group was measured and compared with each other. RESULTS: In both
      semen cells and PMNs, ROS activity increased significantly during the cooling
      process. The highest ROS levels were recorded in both groups when cooled to 4
      degrees C. The ROS levels were extremely low in samples cooled to -20 degrees C
      and in freeze-thaw samples, probably due to marked loss of cell viability.
      CONCLUSIONS: Gradual reduction of temperature during the process of semen
      cryopreservation can cause a significant ROS generation by semen cells. ROS is
      particularly elevated during cooling if the semen sample is contaminated by more
      than 0.5 x 10(6) leukocytes. Removal of leukocytes from semen samples or
      treatment with antioxidants prior to cryopreservation may improve sperm viability
      and function.

PMID- 9187700
TI  - Finasteride and flutamide as potency-sparing androgen-ablative therapy for
      advanced adenocarcinoma of the prostate.
AB  - OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH)
      agonists, orchiectomy, or oral estrogens has significant untoward sexual side
      effects. We evaluated a combination of finasteride and flutamide as potency
      sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the
      prostate. In addition, we evaluated whether finasteride provided additional
      intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced
      prostate cancer were given flutamide, 250 mg orally three times daily. Serum
      prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA
      value, finasteride, 5 mg orally every day, was added. PSA values were then
      measured weekly until a second nadir PSA value was achieved. Sexual function was
      evaluated at baseline, at the second nadir PSA value, and every 3 months
      thereafter. Testosterone, dihydrotestosterone (DHT), and
      dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the
      first and second nadir PSA values. RESULTS: The median follow-up period was 16.9
      months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an
      additional response to subsequent LHRH agonist therapy was observed. One patient
      developed National Cancer Institute grade 3 diarrhea and was withdrawn from the
      study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild
      transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2
      ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second
      PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value
      from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both
      flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline.
      At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11
      were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were
      potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent.
      With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P =
      0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged.
      With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06,
      not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P =
      0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as
      AAT for advanced prostate cancer. Finasteride provided additional intraprostatic
      androgen blockade to flutamide, as measured by additional PSA suppression. Sexual
      potency was preserved initially in most patients, although there was a reduction
      in potency and libido in some patients on longer follow-up. Further evaluation of
      this therapy is needed.

PMID- 9187702
TI  - Epididymal cystadenomas in von Hippel-Lindau disease.
AB  - OBJECTIVES: Epididymal cystadenomas (ECs) are frequently found in association
      with von Hippel-Lindau disease (VHL), but little has been reported about their
      sonographic appearance. We review the sonographic appearance of ECs, the
      relationship of ECs to other manifestations of VHL, and the specific genetic
      mutations associated with ECs. METHODS: Fifty-six male patients with VHL were
      examined with scrotal sonography and physical examination as part of a larger
      screening program for VHL. The head of the epididymis was measured in two planes
      on sonography and compared with age-matched normal controls. All VHL patients
      with palpable epididymal abnormalities or enlargement (more than two standard
      deviations) of the head of the epididymis on ultrasound were considered positive
      for EC. RESULTS: Thirty of 56 (54%) male patients with VHL demonstrated a
      unilateral (n = 10; 33%) or bilateral (n = 20; 67%) solid abnormality in the head
      of the epididymis suggestive of EC. Sonographic appearances ranged from a solid
      mass with multiple tiny cysts to an almost completely solid mass. The most common
      appearance was a 15- to 20-mm solid mass with small cystic components. Dilated
      efferent ductules were seen within the testicle in 7 men, evidently a result of
      chronic obstruction. There was no association between the clinical subtype of VHL
      and the presence of ECs (P > 0.10, chi square). Mutations resulting in a
      truncated gene product were associated with the development of ECs but the
      association did not reach statistical significance (P = 0.06). CONCLUSIONS: ECs
      are a common manifestation of VHL in men and exhibit a range of appearances on
      ultrasound. Sonography can be used to identify ECs and determine the extent of
      cystic dilation of the rete testes. The benign course of ECs and the usual
      absence of clinical symptoms favor a conservative approach to their management.

PMID- 9187703
TI  - Long-term follow-up of patients receiving injection therapy for erectile
      dysfunction.
AB  - OBJECTIVES: During the last decade, vasoactive intracavernosal pharmacotherapy
      (VIP) has been used extensively for the treatment of erectile dysfunction.
      However, there is concern about high discontinuation rates and the possibility of
      long-term complications. Because of few long-term studies on VIP, we investigated
      efficacy, side effects, satisfaction index, and drop-out rate for injection
      therapy in patients who started treatment more than 5 years ago. METHODS:
      Questionnaires were mailed to 108 patients who were started on VIP more than 5
      years ago, between November 1984 and July 1989. The hospital records and data
      from the 100 responders (93%) were reviewed. RESULTS: Only 32% of the patients
      continue to use VIP. Most (56%) of those who discontinued did so during the first
      year. The patients cited one or more of the following reasons for
      discontinuation: desire for a permanent modality of therapy (29%), lack of a
      suitable partner (26%), fear of needles (23%), poor response (23%), fear of
      complications (22%), and lack of sexual spontaneity (21%). This study, which has
      one of the longest follow-up periods in the literature, has significant new
      findings in three areas: discontinuation rates fall after 2 years, long-term
      complications are relatively minor, and patients who discontinue therapy are
      significantly older or have a poor initial impression of VIP. Paradoxically,
      discontinuing VIP was apparently unrelated to side effects or etiology of
      erectile dysfunction, and 82% of patients would still recommend VIP to a friend.
      CONCLUSIONS: This study conclusively shows that because of high initial
      satisfaction and relatively minor side effects, VIP should remain as one of the
      initial options for long-term treatment of erectile dysfunction. However, despite
      seemingly doing well, patients often discontinue therapy, and therefore should be
      followed closely so that alternative therapy can be offered.

PMID- 9187704
TI  - Principles in management of complex pediatric genitourinary plexiform
      neurofibroma.
AB  - Neurofibromatosis is a hamartomatous disorder of neural crest derivation
      characterized by cutaneous pigmentation and tumor formation in various tissues.
      Visceral involvement is typically insidious, progressive, and difficult to treat.
      Plexiform neurofibroma of the urinary tract is rare. Involvement of nearly every
      genitourinary structure by these lesions has been reported, with the bladder
      being most commonly involved. In part due to the small number of patients seen at
      any one institution and the highly variable location and extent of this disease
      process, a plan for management of individuals with genitourinary
      neurofibromatosis has not been proposed. In an attempt to define specific goals
      in treatment of such patients, we reviewed our population of 260 pediatric
      patients with type 1 neurofibromatosis. We present our series of 5 patients with
      complex genitourinary lesions and describe specific management principles.

PMID- 9187705
TI  - Surgical management of persistent mullerian duct syndrome.
AB  - OBJECTIVES: To describe the optimal surgical management of the testes and
      mullerian duct structures in patients with persistent mullerian duct syndrome.
      METHODS: We performed a comprehensive Medline literature search regarding the
      surgical management of persistent mullerian duct syndrome and extracted
      information regarding the etiology, pathogenesis, and treatment of this disorder.
      We specifically assessed the risks of retained mullerian structures versus
      surgical excision of the infantile uterus and fallopian tubes. Using this
      information, we formulated a comprehensive strategy for the management of
      patients with persistent mullerian duct syndrome. An illustrative case is
      described. RESULTS: No malignant degeneration of persistent mullerian structures
      has been reported. The risk of testicular neoplasia in persistent mullerian duct
      syndrome approximates the risk of neoplasia in other intra-abdominal gonads.
      Fertility has rarely been reported although virilization is unaffected. Surgical
      excision of the infantile uterus and fallopian tubes risks damage to vasa
      deferentia and the deferential blood supply to the testis. CONCLUSIONS: Surgical
      excision of persistent mullerian duct structure may result in ischemic and/or
      traumatic damage to the vasa deferentia and testes. Optimal surgical management
      is orchiopexy leaving the uterus and fallopian tubes in situ. Meticulous proximal
      salpingectomy and hysterectomy is indicated only in patients whose mullerian
      structures limit intrascrotal placement of the tests. Orchiectomy is indicated
      for testes that cannot be mobilized to a palpable location.

PMID- 9187706
TI  - Use of a surgical sponge facilitates rib resection in flank incisions.
AB  - Dissection of the rib in a flank incision is often tedious and difficult. Entry
      into the pleural space and subcostal nerve injury are two frequent complications.
      In an effort to reduce the frequency of these complications and to facilitate the
      ease of rib dissection and resection, we describe a technique that uses a
      moistened surgical sponge to dissect free the posterior surface of the rib.

PMID- 9187707
TI  - A new strategy for management of retroperitoneal tumors with supradiaphragmatic
      vena caval thrombi.
AB  - A new surgical technique to treat retroperitoneal tumors with supradiaphragmatic
      vena caval invasion is described. In this technique, hepatic warm ischemia can be
      avoided with reversed hepatic outflow through the portal vein and neither
      hypothermic circulatory arrest nor cardiopulmonary bypass is necessary using
      centrifugal blood pump-driven bypass.

PMID- 9187708
TI  - Clinical and radiologic findings in schistosomiasis of the bladder.

PMID- 9187709
TI  - Vesicovasal reflux: an imaging quandary.

PMID- 9187710
TI  - Ureteroscopic diagnosis of intraluminal metastatic rectal carcinoma.
AB  - Ureteral obstruction resulting from metastatic adenocarcinoma is almost always
      extrinsic in nature. In contrast, true intraluminal metastases are extremely
      rare. With this report, we document the videoendoscopic appearance of true
      intraluminal ureteral metastases from metastatic rectal cancer confirmed with
      histopathologic examination. The value of transureteroscopic biopsy for accurate
      diagnosis is also demonstrated.

PMID- 9187711
TI  - Primary osteosarcoma of the spermatic cord with synchronous bilateral renal cell
      carcinoma.
AB  - Primary extraskeletal osteosarcoma of the spermatic cord is an extremely rare
      tumor with only two other cases being reported in the world literature. We
      describe a patient with this lesion who also had concomitant bilateral renal cell
      carcinoma. The management of this case and a review of this subject are
      presented.

PMID- 9187712
TI  - Genitourinary neurofibromatosis mimicking posterior urethral valves.
AB  - A 12-year-old boy, examined after an episode of acute urinary retention, was
      found to have neurofibromatosis of the bladder neck and prostatic urethra. His
      symptoms of bladder outlet obstruction and radiographic findings of a dilated
      prostatic urethra mimicked posterior urethral valves. Complete urologic
      investigation, including cystourethroscopy, revealed that the dilatation of the
      prostatic urethra was secondary to neural involvement of the external sphincter
      and posterior urethra without mechanical obstruction or posterior urethral
      valves.

PMID- 9187713
TI  - The malone antegrade continence enema combined with urinary diversion in adult
      neurogenic patients: early results.
AB  - OBJECTIVES: Patients with neurogenic voiding dysfunction often have coexisting
      neurogenic bowel problems. Impaired bowel evacuation is a cause of major
      morbidity and impaired lifestyle for these patients. The Malone antegrade
      continence enema (ACE) performed synchronously with a urinary continence
      procedure has been successful in pediatric patients. We report early experience
      combining the ACE with a urinary continence procedure in adult neurogenic
      patients. METHODS: Adult patients with neurogenic voiding dysfunction and
      impaired bowel evacuation refractory to conservative management underwent a
      urinary continence procedure synchronously with an ACE. RESULTS: Two patients
      have undergone the procedure. One patient chose a continent catheterizable
      supravesical bladder augmentation, whereas the other patient chose an ileal
      conduit. Both patients had a separate appendiceal stoma for their ACE. Both
      patients are continent of stool at their appendiceal stoma and per rectum. Both
      patients have stabilized their urinary tracts. Complications were minimal.
      CONCLUSIONS: The ACE may benefit adult patients with impaired bowel evacuation
      and may be combined with a urinary continence procedure. Further study of the ACE
      is warranted.

PMID- 9187714
TI  - Perineural invasion in transitional cell carcinoma and the effect on prognosis
      following radical cystectomy.
AB  - OBJECTIVES: The relationship between perineural invasion and prognosis has been
      demonstrated to be poor in a number of malignancies. This has not been evaluated
      in the bladder. We performed a study to determine the occurrence of nodal
      metastases, extranodal metastases, and disease-free survival in patients with
      perineural invasion (PNI) and/or angiolymphatic invasion (ALI) in transitional
      cell carcinoma of the bladder (TCCB) from radical cystectomy specimens. METHODS:
      A retrospective review of 27 patients treated with radical cystectomy for TCCB
      was conducted. Comparisons were performed between three groups: PNI with or
      without ALI (PNI +/- ALI, 12 patients), ALI alone (8 patients), and a control
      group (no PNI or ALI) (7 patients). RESULTS: The mean patient age was 70 years
      (range 49 to 83). The overall median follow-up period was 11 months (range 1 to
      32). PNI +/- ALI was predominantly found in Stage T3b disease (14 of 20 [70%]
      cases). The overall 1-year disease-free survival was 48%, 67%, and 83% for the
      PNI +/- ALI, ALI alone, and control groups, respectively. Nodal metastases (for
      all stages combined) were found in 6 of 12 (50%), 3 of 8 (38%), and 1 of 7 (14%)
      patients in the PNI +/- ALI, ALI alone, and control groups, respectively.
      Similarly, extranodal metastatic disease was found in 5 of 12 (42%), 4 of 8
      (50%), and 1 of 7 (14%) patients in the PNI +/- ALI, ALI alone, and control
      groups, respectively. The percentage of deaths for the PNI +/- ALI, ALI only, and
      control groups were 33%, 50%, and 14%, respectively. CONCLUSIONS: In TCCB,
      perineural invasion with or without angiolymphatic invasion and angiolymphatic
      invasion alone are associated with a higher incidence of nodal and extranodal
      metastases and death.

PMID- 9187715
TI  - Epidermal growth factor suppresses renal tubular apoptosis following ureteral
      obstruction.
AB  - OBJECTIVES: Acute unilateral ureteral obstruction (UUO) results in ipsilateral
      hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA
      expression and EGF protein levels in the distal renal tubules. UUO results in
      programmed cell death with increases in the characteristic markers of apoptosis.
      To suppress the apoptotic response during UUO, recombinant EGF was administered
      during renal obstruction and the ensuing molecular and histologic changes were
      studied. METHODS: Mature Sprague-Dawley rats underwent left ureteral obstruction
      and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis
      included DNA laddering pattern on agarose gel electrophoresis, in situ gap
      labeling of fragmented DNA for quantitative apoptotic body determination,
      polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated
      glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following
      administration of 10, 20, and 40 micrograms of subcutaneous recombinant EGF on a
      daily basis after UUO. RESULTS: Subcutaneous injection of EGF into unilaterally
      obstructed rats promotes renal tubular epithelial cell regeneration, as
      demonstrated by increased cortical mitotic activity. Systemic EGF supplementation
      in these unilaterally obstructed rats also resulted in a decrease in the
      intensity of the DNA laddering pattern associated with renal tubular apoptosis.
      An in situ labeling procedure to identify apoptotic nuclei in the ureterally
      obstructed kidneys revealed a 50% reduction in apoptosis after EGF
      administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA
      or clustering gene product also revealed a decreased expression in the obstructed
      and EGF-treated renal parenchyma. CONCLUSIONS: These data suggest that EGF, apart
      from its known role as a mitogenic substance for renal tubular epithelial cells,
      is also a critical in vivo renal cell survival factor for the developmentally
      mature kidney.

PMID- 9187718
TI  - Skeptical thinking for food animal veterinarians.

PMID- 9187717
TI  - Federal agencies collaborate to control dangerous new Salmonella strain.

PMID- 9187719
TI  - What is your diagnosis? Osteochondromatosis.

PMID- 9187720
TI  - Relationship between soil type and Mycobacterium paratuberculosis.

PMID- 9187721
TI  - Veterinarians and their human clients.

PMID- 9187716
TI  - A simple method for the isolation and culture of epithelial and stromal cells
      from benign and neoplastic prostates.
AB  - OBJECTIVES: Current primary prostate cell culture techniques use an overnight
      digestion or extensive media preparation. In this report, we describe a method
      for the culture of benign and neoplastic cells from human prostatectomy specimens
      that is rapid and contains no undefined factors in the medium. METHODS:
      Characterization of the human cultured prostate cells was performed using
      immunohistochemical methods and monoclonal antibodies AE1/AE3 and cytokeratin 8,
      as well as monoclonal antibodies against prostate-specific antigen (PSA).
      Polymerase chain reaction was used to measure the exclusive epithelial and
      stromal cell products, c-met and hepatocyte growth factor (HGF), respectively.
      Electron microscopy was performed to assess the cell junctions and morphologic
      features of epithelial cells. Optimum cell growth in different media was tested
      using a cell replication assay. RESULTS: Microscopic evidence revealed that the
      cells demonstrate typical epithelial morphology, with polyhedral cells forming
      tight junctions in a continuous monolayer. Desmosomes were present in electron
      micrographs of epithelial cells. The cultured epithelial cells described in this
      report also demonstrate positive cytokeratin staining. The epithelial cells
      reacted positively with PSA antibody, indicating that the cells retain their
      secretory role in cell culture for a limited period. Epithelial cells expressed
      the HGF receptor, c-met; stromal cells secreted HGF. Insulin, transferrin, and
      selenium increased the growth of cells in the chemically defined media, compared
      with minimum essential media (MEM) and Ham's F12. CONCLUSIONS: In summary,
      essentially pure cultures of prostate stromal or epithelial cells have been
      established using simple isolation and culture methods. These cells will be
      useful for the investigation of related growth factors, such as insulin-like
      growth factor I and insulin-like growth factor II, and in understanding the basis
      for stromal-epithelial cell interactions.

PMID- 9187722
TI  - Veterinary practice expenses.

PMID- 9187723
TI  - Development of bone marrow toxicosis after albendazole administration in a dog
      and cat.
AB  - Bone marrow toxicosis was detected in a dog and cat following albendazole
      administration. Both animals were admitted with pancytopenia. In the dog,
      pancytopenia was attributed to severe panmarrow hypoplasia, whereas the cat had
      hypoplasia of erythroid and megakaryocytic series, but with a left-shifted
      granulocytic hyperplasia. Results of cytologic examination of bone marrow from
      both animals were compatible with acute injury. Both animals had been treated
      with albendazole for giardiasis prior to the onset of clinical signs. Bone marrow
      toxicosis was attributed to albendazole administration for the following reasons:
      this was the only or most recent drug administered, other causes of bone marrow
      toxicosis were not found, and both animals recovered rapidly with supportive care
      that consisted of fluid and antibiotic administration. Albendazole induced
      toxicosis appeared to be dose related in the dog and idiosyncratic in the cat. On
      the basis of the findings in this report, there is a potential for the
      development of albendazole induced bone marrow toxicosis in dogs and cats;
      therefore, veterinarians should exercise caution when using this drug.

PMID- 9187724
TI  - High feline trypsin-like immunoreactivity in a cat with pancreatitis and hepatic
      lipidosis.
AB  - A 1.5-year-old domestic shorthair cat was examined because of vomiting and
      icterus. Clinicopathologic abnormalities included high alanine transaminase,
      alkaline phosphatase, and gamma-glutamyltransferase activities and high total
      bilirubin concentration. During abdominal ultrasonography, the left limb and body
      of the pancreas appeared hypoechoic, and a small quantity of peritoneal effusion
      was seen. The liver was diffusely hyperechoic, with echogenicity similar to that
      of the spleen, indicating hepatic lipidosis. Feline trypsin-like immunoreactivity
      was high, suggesting that the cat also had pancreatitis. The cat was treated with
      crystalloid fluids and was fed a protein-restricted diet via a percutaneous
      endoscopically placed gastrostomy tube. The cat's condition continued to
      deteriorate despite medical treatment, and it was euthanatized. Necropsy
      confirmed the clinical suspicion of acute pancreatitis and hepatic lipidosis.
      This case suggests that measurement of trypsin-like immunoreactivity may be
      useful in cats suspected of having pancreatitis.

PMID- 9187725
TI  - Long-term results of surgical correction of persistent right aortic arch in dogs:
      25 cases (1980-1995).
AB  - OBJECTIVE: To evaluate long-term outcome of dogs with persistent right aortic
      arch that undergo surgical correction. DESIGN: Retrospective study. ANIMALS: 25
      dogs. PROCEDURE: Surgical correction consisted of ligation and division of the
      ligamentum arteriosum through a left fourth intercostal thoracotomy. Long-term (>
      6 months after surgery) follow-up information was obtained by means of a
      telephone survey of owners (22 dogs) and by means of reevaluations by a
      veterinarian (3). RESULTS: Median age at the time of surgical treatment was 12
      weeks. Short-term (2 to 4 weeks after surgery) follow-up information was
      available for 14 dogs. Nine no longer regurgitated after eating, and 5
      regurgitated infrequently. Follow-up esophagography (median time after surgery, 4
      months) was performed in 13 dogs and revealed persistence of megaesophagus in all
      13. At the time of long-term follow-up, 23 (92%) dogs no longer regurgitated
      after eating, and the remaining 2 (8%) had regurgitated less than once per week.
      CLINICAL IMPLICATIONS: Contrary to previous reports, surgical correction of
      persistent right aortic arch resulted in complete alleviation of clinical signs
      in most dogs and an improvement in signs in the remaining dogs. Persistence of
      megaesophagus and regurgitation in the early postoperative period did not
      indicate a poor long-term outcome.

PMID- 9187726
TI  - Complications associated with use of jejunostomy tubes in dogs and cats: 40 cases
      (1989-1994).
AB  - OBJECTIVE: To evaluate complications and outcomes of surgeries in which
      jejunostomy tubes were used in critically ill dogs and cats. DESIGN:
      Retrospective review of medical records. ANIMALS: 32 dogs and 8 cats. PROCEDURE:
      In each animal, a 5-F or 8-F red rubber urethral/feeding catheter was surgically
      placed in the proximal portion of the jejunum. RESULTS: The most common
      indication for jejunostomy tube placement in dogs was a gastrointestinal
      condition (20 dogs; 62.5%). Neoplasms were detected in 11 of the 20 dogs.
      Pancreatic disease was the most common indication for tube placement in cats (7
      cats; 87.5%). Thirty-three animals (27 dogs, 6 cats; 82.5%) did not have
      complications. Five dogs and 2 cats had 10 tube-related complications, including
      focal cellulitis (3 dogs), tube dislodgement (2 dogs, 1 cat), and tube occlusion
      (1 dog, 1 cat). Twenty-four animals (20 dogs, 4 cats; 60%) were discharged from
      the hospital. Fifteen dogs and 4 cats were alive 2 weeks after discharge, and 5
      dogs and 2 cats survived for at least 4 weeks after discharge. Deaths were
      related to disease and were not associated with jejunostomy tubes. CLINICAL
      IMPLICATIONS: The complication rate associated with jejunostomy tubes appears to
      be low. Complications usually are nonfatal.

PMID- 9187727
TI  - Use of tenoscopy for management of septic tenosynovitis caused by a penetrating
      porcupine quill in the synovial sheath surrounding the digital flexor tendons of
      a horse.
AB  - A 6-year-old Quarter Horse gelding with acute onset of a grade-4/5 lameness of
      the left forelimb 21 days after an encounter with a porcupine was examined.
      Quills had been removed by the referring veterinarian, and the horse had been
      treated with antibiotics and hydrotherapy for 14 days. The horse was pyretic and
      had effusion in the digital synovial sheath. Signs of pain were elicited on
      palpation of the area. A tentative diagnosis of septic tenosynovitis caused by a
      porcupine quill was made. Exploratory tenoscopy revealed large amounts of fibrin
      in the sheath and a 1.2-cm quill. Bacteriologic culture of synovial fluid yielded
      a pure growth of Staphylococcus aureus. The horse improved dramatically after
      tenoscopic removal of the quill, debridement of fibrin, and lavage to dilute
      inflammatory mediators and bacteria, debridement of fibrin, discovery and removal
      of a quill, and complete evaluation of the sheath for prognostic purposes.
      Tenoscopy can provide a means for direct observation and enhance the ability of
      clinicians to debride a septic synovial sheath in a minimally invasive manner.

PMID- 9187728
TI  - Use of yohimbine to reverse prolonged effects of xylazine hydrochloride in a
      horse being treated with chloramphenicol.
AB  - A 1-year-old Standardbred gelding had received xylazine hydrochloride (0.75 to
      1.00 mg/kg [0.34 to 0.45 mg/lb] of body weight, IV) during 2 surgeries for
      debridement of a wound. The horse was given chloramphenicol (55 mg/kg [25 mg/lb],
      PO, q 6 h) for 5 days, and was anesthetized a third time with xylazine (0.75
      mg/kg, IM). Five hours after administration of xylazine, the horse remained
      markedly sedated and had clinical signs of gaseous distention of the large bowel
      (bloat) requiring trocharization. Administration of yohimbine (0.03 mg/kg [0.01
      mg/lb], i.v.) eliminated signs of sedation within 5 minutes. Moderate flatulence
      developed, and gastrointestinal sounds could be heard within all 4 abdominal
      quadrants within 15 minutes of yohimbine administration. The remainder of
      recovery was unremarkable. Xylazine induces bradycardia and decreases
      gastrointestinal motility in addition to causing sedation, muscle relaxation, and
      analgesia. Chloramphenicol can inhibit oxidase activity of cytochrome P-450 and
      inhibit metabolism and elimination of drugs such as xylazine.

PMID- 9187729
TI  - Acute hemorrhagic pulmonary infarction and necrotizing pneumonia in horses: 21
      cases (1967-1993).
AB  - OBJECTIVE: To characterize history, clinical signs, and pathologic findings in
      horses with histologically confirmed acute hemorrhagic pulmonary infarction and
      necrotizing pneumonia. DESIGN: Retrospective study. ANIMALS: 21 horses. RESULTS:
      19 of the 21 horses were Thoroughbred racehorses in training. Eighteen horses had
      had strenuous exercise immediately prior to onset of illness. Fifteen horses had
      a serosanguineous nasal discharge during hospitalization. Seventeen horses had
      radiographic evidence of pulmonary consolidation and pleural effusion. Nine of 14
      horses had ultrasonographic evidence of large pulmonary parenchymal defects
      consistent with consolidation. Pleurocentesis yielded a suppurative,
      serosanguineous effusion in the 14 horses in which it was performed. Bacteria
      were isolated from all transtracheal aspirates (14) and from 6 of 12 pleural
      fluid samples. Actinobacillus suis-like organisms and Streptococcus equi subsp
      zooepidemicus were most commonly isolated. Nineteen horses were hospitalized and
      treated. Mean duration of treatment was 5 days, and most horses were euthanatized
      because of secondary complications, continued costs of medical treatment, or poor
      prognosis for future performance. Pathologic lesions included well-demarcated
      regions of hemorrhagic pulmonary infarction with necrosis and a serosanguineous
      pleural effusion. Thrombosis of pulmonary vessels was found in 11 horses.
      CLINICAL IMPLICATIONS: An acute or peracute onset of severe respiratory distress,
      with serosanguineous nasal discharge, ultrasonographic and radiographic evidence
      of severe pulmonary consolidation, and serosanguineous suppurative pleural
      effusion, is strongly suggestive of pulmonary infarction in horses. Horses with
      pulmonary infarction responded poorly to conventional treatment for
      pleuropneumonia and had a poor prognosis for recovery.

PMID- 9187730
TI  - Milk production and reproductive performance in dairy cows given bovine
      respiratory syncytial virus vaccine prior to parturition.
AB  - OBJECTIVE: To assess the effect of vaccination against bovine respiratory
      syncytial virus on milk production, reproductive performance, and health in
      lactating dairy cows. DESIGN: Prospective randomized block design. ANIMALS: 385
      Holstein dairy cows and heifers. PROCEDURE: Cows were grouped by lactation
      number, season of calving, and previous mature equivalent 305-day milk production
      (where appropriate). Prior to parturition, cows and heifers were randomly
      assigned to be vaccinated i.m. against infectious bovine rhinotracheitis, bovine
      viral diarrhea, and parainfluenza 3 viruses by use of a three-way vaccine, or to
      be vaccinated against those viruses as well as bovine respiratory syncytial
      virus, using a four-way vaccine. Milk production was measured daily through 305
      days of lactation. Reproductive and medical records were reviewed to obtain
      insemination dates and record medical problems of cows in each vaccine treatment
      group. RESULTS: Compared with the three-way vaccine, administration of the four
      way vaccine was associated with higher milk production (1.39 kg [3.06 lb] more
      milk/d) in first-parity cows during the first 21 weeks of lactation. Vaccination
      did not have any effect on milk production after the first 21 weeks of lactation
      in cows of any parity. Conception rates at first insemination were higher for
      four-way vaccinated first-parity cows than for three-way vaccinated first-parity
      cows (54.6 vs 32.7%). Compared with second-parity cows that received the three
      way vaccine, first insemination conception rate was improved for second-parity
      cows vaccinated with the four-way vaccine (28.9 vs 47.8%, respectively). In cows
      of third or greater parity, first insemination conception rate was not different
      between the 2 vaccine treatment groups. CLINICAL IMPLICATIONS: Vaccination of
      heifers against bovine respiratory syncytial virus prior to partrition may
      increase milk production and first insemination conception rates.

PMID- 9187731
TI  - Ocular diseases of llamas: 194 cases (1980-1993)
AB  - OBJECTIVE: To identify ocular and adnexal diseases to which llamas in North
      America are susceptible, to determine prevalence of these diseases in llamas, and
      to compare prevalences of the major ocular diseases of llamas, cattle, and
      horses. DESIGN: Retrospective study. ANIMALS: 194 llamas, 4,937 cows, and 11,950
      horses with ocular disease. PROCEDURE: Medical records of all llamas entered into
      the Veterinary Medical Database between 1980 and 1993 were reviewed. Data on
      ocular structures affected and types of ocular disease were compiled. Prevalences
      of uveitis, corneal ulcers, and ocular squamous cell carcinoma in llamas were
      compared with prevalences in cattle and horses. RESULTS: 194 of 3,243 (6%) llamas
      had at least 1 ocular disease. The proportion of llamas that had ocular disease
      was significantly higher than the proportions of cattle or horses. The most
      frequently affected ocular structure in llamas was the cornea, and ulcerative
      keratitis was the most common corneal disease. The second most commonly affected
      structure was the uveal tract. Cataracts were reported in 20 (10%) of the llamas
      with ocular problems. Eyelid disorders, retinal diseases, glaucoma, and ocular or
      adnexal neoplasia were reported infrequently in llamas. CLINICAL IMPLICATIONS:
      Results suggest that corneal disease is common in llamas and is usually secondary
      to trauma. Uveitis may also be common in llamas, but llamas do not appear to be
      highly susceptible to glaucoma, ocular neoplasia, or to direct corneal invasion
      by bacteria such as Moraxella sp.

PMID- 9187732
TI  - Staining tomato fruit cuticle and exocarp tissues.
AB  - Immature fruit of tomato, Lycopersicon esculentum (Celebrity), was examined to
      observe the cuticle, its interface with the epidermis, and the general histology
      of the outer exocarp. Paraffin sections were stained first with Bismarck brown Y.
      Structures already stained in various hues of brown were stained again with
      either azure B, aluminum hematoxylin and alcian blue SGX, or the periodic acid
      Schiff (PAS) reaction. Bismarck brown-azure B displayed the cuticle in strong
      contrast with subjacent tissue; however, nuclei were not easily identified at low
      magnification. Bismarck brown-hematoxylin-alcian blue produced a sharply
      contrasted combination of yellow cuticle, bright blue cell walls and purple
      nuclei. Nuclei stained purple with hematoxylin were easily identified at x100.
      Bismarck brown-PAS stained the cuticle golden brown and subjacent tissues mageta
      red. Surprisingly, epidermal cells stained specifically and intensely with PAS
      while pretreatment with an aldehyde blockade and omission of periodic acid
      prevented staining of all other tissues.

PMID- 9187734
TI  - Improved methods for making and using glass knives.
AB  - We have observed over time that the right side of a glass knife is the optimal
      cutting edge for microtomy if the counterpiece (heel opposite the edge) is
      controlled within 1 mm. The right cutting edge has been considered the "saw
      toothed" side and has not been used for ultrathin sectioning. We have observed
      that the right cutting edge is sharper and more durable than the left. Light and
      scanning electron microscopy were used to observe the cutting edge, and
      transmission electron microscopy was used to examine semithin and ultrathin
      sections of animal and plant tissues cut by the right and left sides of the
      cutting edge. The results indicate that the cutting edge becomes sharper and more
      durable from left to right. Both the quality and efficiency of ultrathin
      sectioning is improved by using the right cutting edge.

PMID- 9187733
TI  - Retention in situ and spectral analysis of fluorescent vacuole components in
      sections of plant tissues.
AB  - The contents of plant vacuoles vary in different organs and with the health of
      the plant, but little is known of the cell-to-cell distribution of soluble
      organic compounds within plant tissues. Soluble fluorescent phenolic compounds
      can be immobilized in plant tissues using an anhydrous freeze-substitution and
      resin embedment process. The vacuolar fluorescence can be characterized in
      fluorescence photomicrographs for variations in color and intensity, or more
      quantitatively with spectra obtained using a microspectrofluorometer. This is
      demonstrated here in freeze-substituted roots and leaves of soybean. Excitation
      and emission spectra of individual vacuoles can be compared with spectra of pure
      compounds to form profiles of the varied phenolic contents of plant vacuoles.
      Such analyses will add an important anatomical dimension to the study of plant
      defense and stress responses.

PMID- 9187735
TI  - Identification of medieval human soft tissue remains in an advanced state of
      decomposition.
AB  - Naturally preserved human soft tissue remains from mediaeval burials (11-13th
      century A. D.) were investigated histologically after azocarmine/aniline alcohol
      (AZAN) or keratinprekeratin-mucin (KPM) staining. The tissue remnants were in an
      advanced state of decomposition; they were completely collapsed and had lost
      their macroscopic characteristics. After rehydration, thin sectioning, and
      staining, microscopic properties permitted tissue identification, although
      differential staining of tissue components did not necessarily correspond with
      the expected results based on fresh tissue. The techniques and results presented
      in this paper are relevant for both anthropological and forensic purposes.

PMID- 9187736
TI  - Rapid denaturation improves chromosome morphology and permits multiple
      hybridizations during fluorescence in situ hybridization.
AB  - Denaturation of chromosomal DNA for fluorescence in situ hybridization (FISH) is
      an essential step in a procedure associated with a number of variables. In our
      experience, shorter denaturation time in 70% formamide/2 x SSC at 72 C provides
      sufficient denaturation, where the hydrogen bonds are broken between the purines
      and pyrimidines of the double helix. This shortened exposure improves retention
      of morphology of human chromosomes from lymphocytes, aminocytes, fibroblasts and
      bone marrow, and allows the same metaphases to be denatured repeatedly and
      rehybridized with different probes. This approach is useful in investigations
      where sample volume is limited.

PMID- 9187737
TI  - Microwave fixation of whole fetal specimens.
AB  - This study compares microwave fixation of whole fetal specimens with conventional
      techniques performed at room temperature. All fetuses were obtained from the same
      pregnant rat; half of them were placed in neutral formalin for 15 min at room
      temperature, then irradiated for 2.5 min in a domestic microwave oven. The
      remaining fetuses were placed in neutral formalin at room temperature for 48 hr
      as a control. Both experimental and control groups were exposed to routine tissue
      processing for light microscopy and embedded in paraffin wax. Sections 5 microns
      thick were stained with hematoxylin and eosin. Our results showed that the
      microwave technique reduced the fixation time while providing thin sections that
      were equal to or better in quality than those in the control group.

PMID- 9187739
TI  - Whole joint embedding in polymethylmethacrylate: a method for preparing intact
      musculoskeletal organ systems for histomorphology and 3-D reconstruction.
AB  - Large and medium size undecalcified joints were embedded in methylmethacrylate
      resin. Sections of 600 microns prepared from polymethylmethacrylate blocks show
      minimal distortion and are suitable for surface staining and three-dimensional
      reconstruction. The 5 microns sections prepared from these slabs retain good
      cytological detail. This method permits the examination of musculoskeletal organ
      systems at both macroscopic and microscopic levels.

PMID- 9187738
TI  - Effect of fixation on interphase cytogenetic analysis by direct fluorescence in
      situ hybridization on cell imprints.
AB  - The direct fluorescent in situ hybridization (FISH) technique using a
      centromerespecific DNA probe for chromosome 11 was applied on fresh tissue
      imprints from melanomas and pituitary adenomas. The cell imprints were fixed in
      acetone and formalin, and the influence of fixation was evaluated. Acetone fixed
      imprints gave a sharp and intense fluorescent signal in a large number of cells
      from both tumors without any pretreatment. In contrast, formalin fixed imprints
      disclosed a weak hybridization signal in a few cells even after careful enzymatic
      digestion. Direct FISH on acetone fixed cell imprints represents a simple and
      time saving technique applicable to any laboratory for the study of numerical
      chromosomal abnormalities.

PMID- 9187740
TI  - Glycoconjugate saccharidic moieties of the exocrine and endocrine pancreas in the
      chick embryo, newborn and adult.
AB  - A battery of horseradish peroxidase-conjugated lectins (PNA, SBA, DBA, WGA, ConA,
      LTA and UEAI) was used to study the distribution of glycoconjugate sugar residues
      in the exocrine and endocrine pancreas of chick embryos, 1-day-old chicks and
      adult animals. During the period of incubation considered here, the time of
      appearance and changes in the oligosaccharides were noted in the acinar cells, in
      the endocrine cells of the "light islets" and in the capillary endothelial cells.
      In the developing exocrine pancreas, the basolateral surface of the acinar cells
      reacted with PNA, WGA, LTA and ConA for the entire period of incubation while
      SBA, WGA, LTA and ConA reactivity was detected in the apical plasma membrane.
      Zymogen granule membrane reacted with PNA, WGA and LTA from the 12th day onward,
      while ConA reactivity was detectable from the 7th day onward. Owing to its early
      appearance, alpha-D-mannose, revealed by ConA lectin, might in some way
      contribute to the maturation of the zymogen granule. In the 1-day-old chick and
      in the adult the cellular surface reacted with WGA and ConA. The zymogen granule
      membrane reacted with PNA, WGA and ConA in the 1-day-old chick. In the adult, WGA
      and ConA reactivity was observed in the zymogen granule membrane, whereas at this
      site PNA reactivity was revealed only after neuraminidase digestion. The
      hypothesis formulated by others that granule membrane lectin reactivity is equal
      to the apical membrane reactivity, owing to exocytotic processes, is not
      consistent with our results in the chick embryos, the 1-day-old chick and the
      adults. The surface and the granules of the islet beta cells in different periods
      of incubation reacted with WGA, SBA and, after neuraminidase treatment, with PNA.
      The same reactivity was seen also in 1-day-old chick while in the adult the
      granules of the beta cells also reacted with ConA. These findings show the
      achievement of an almost adult-like state of glycosylation of the glycoconjugates
      in the beta cells at an early stages of development.

PMID- 9187741
TI  - Postadhesive technique for archival paraffin sections.
AB  - We present a postadhesive protocol for adhering paraffin sections of archival
      material to microscope slides. Appropriately posttreated sections, subsequently
      processed for immunohistochemistry, remained attached to the slides and were well
      preserved with no signs of artifacts, such as scratching and shrinkage. The
      immunohistochemical staining was intense and antigen-specific without nonspecific
      background. Specific staining intensity was equal to that produced in untreated
      control sections; however, the latter became partially or fully detached from the
      slides. The postadhesion protocol may be used with modern techniques and is
      recommended for reclaiming use of otherwise unsuitable paraffin sections of
      archival material.

PMID- 9187743
TI  - Detection of specific DNA-binding protein in HeLa whole-cell extract.

PMID- 9187742
TI  - In situ trypan blue staining of monolayer cell cultures for permanent fixation
      and mounting.

PMID- 9187744
TI  - Optimized conditions of PacI and SwaI for genomic analysis of X. axonopodis pv.
      vesicatoria by PFGE.

PMID- 9187745
TI  - Screening of yeast transformants by chemiluminescence for detection of secreted
      heterologous proteins.

PMID- 9187746
TI  - Improved cloning vectors for transgene construction.

PMID- 9187748
TI  - Partial inverse PCR: a technique for cloning flanking sequences.

PMID- 9187747
TI  - PCR strategy to obtain the 5' and 3' flanking sequences of partial clones from
      lambda ZAP cDNA libraries.

PMID- 9187749
TI  - Refinements in re-amplification and cloning of DDRT-PCR products.

PMID- 9187750
TI  - PCR mutagenesis: treatment of the megaprimer with mung bean nuclease improves
      yield.

PMID- 9187751
TI  - Production of PCR mimics for any semiquantitative PCR application.

PMID- 9187752
TI  - Effects of gelatin and BSA on the amplification reaction for generating RAPD.

PMID- 9187753
TI  - Determination of fibroblast growth factor receptor expression in mouse, rat and
      human samples using a single primer pair.

PMID- 9187754
TI  - Analysis of primer-derived, nonspecific amplification products in RAPD-PCR.

PMID- 9187755
TI  - Isolation of thermophilic bacteria using bacteriological grade agar at
      temperatures above 80 degrees C.

PMID- 9187756
TI  - Extraction of DNA using monoclonal anti-DNA and magnetic beads.

PMID- 9187757
TI  - Rapid isolation of total RNA from small samples of hypocellular, dense connective
      tissues.

PMID- 9187758
TI  - Evaluation of DNA sequencing ambiguities using tetramethylammonium chloride
      hybridization conditions.

PMID- 9187759
TI  - Simultaneous in situ detection of apoptosis and necrosis in monolayer cultures by
      TUNEL and trypan blue staining.
AB  - A method for simultaneously detecting membrane permeability (characteristic of
      necrosis) and DNA fragmentation (characteristic of apoptosis) is described. By
      combining a common dye-exclusion method (Trypan Blue) with a commercially
      available terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end
      labeling (TUNEL) labeling kit, we have succeeded in developing a novel
      methodology for obtaining permanently mounted slides of monolayer cell cultures
      double-labeled for DNA fragmentation and cell lysis. This method should
      facilitate in situ studies of cell death by allowing for a more accurate
      quantification of total toxicity in monolayer cell cultures and perhaps further
      enhance our understanding of the different mechanisms of cell death as well.

PMID- 9187760
TI  - High-throughput RT-PCR analysis of multiple transcripts using a microplate RNA
      isolation procedure.
AB  - We have developed a high-throughput, multiplex reverse transcription PCR (RTPCR)
      assay that is suitable for the analysis of medium-to low-copy cellular RNA
      transcripts from small numbers of cells (10(4)). High throughput was attained by
      utilizing microplate-based RNA extraction and RTPCR protocols, followed by PCR
      product visualization of a multiwelled agarose gel, stained with SYBR Green I
      dye. The transcriptional assay was unaffected by solvents (dimethyl sulfoxide and
      methanol) routinely used in high-throughput drug screens at concentrations
      required for compound solubilization. Furthermore, it has been used successfully
      for the investigation of differential mRNA expression levels of tumor necrosis
      factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta) in lipopolysaccharide
      (LPS)-stimulated THP-1 cells (a human monocytic cell line) and the identification
      of specific IL-1 beta transcriptional inhibitors.

PMID- 9187761
TI  - Isolation of high molecular weight DNA for reliable genotyping of transgenic
      mice.
AB  - A fast and reliable method for the PCR characterization of DNA from mouse toes is
      described. The toes biopsied to tag the mice are incubated for 2 h in proteinase
      K and heated for 15 min at 95 degrees C. This DNA solution is directly used as a
      template for PCR amplification. The same procedure can be used for PCR analysis
      of DNA from other tissues in adult mice, mouse embryos and cultured cells.
      Because of minimal tissue manipulation, high-quality and high-molecular-weight
      DNA (fragments larger than 100-200 kb) is isolated. This procedure is performed
      in a single tube and requires no organic solvent extraction or centrifugation,
      allowing the isolation of high-molecular-weight DNA suitable for PCR
      amplification in a fast and reproducible way. Only the tissue excised during mice
      tagging is used and a large number of animals can be quickly and simultaneously
      analyzed as required to maintain a transgenic mice colony. In addition, this
      rapid and efficient procedure represents an alternative to other methods in
      which, in our experience, inhibition of the PCR amplification occurs when DNA
      from tail tissues is used.

PMID- 9187762
TI  - Analysis of the size distribution of first-strand cDNA molecules.
AB  - We have developed a method to analyze the size distribution of the first-strand
      cDNA molecules corresponding to given mRNA species. First-strand molecules
      synthesized from cytoplasmic polyadenylated RNAs are separated by electrophoresis
      on an alkaline agarose gel, and a Southern blot hybridization is performed. As an
      example, we analyzed the first-strand molecules corresponding to the human c-myc
      mRNAs. This method can be used to determine whether full-length, first-strand
      molecules corresponding to an mRNA species to be cloned are synthesized
      efficiently. Interestingly, this method allows one to analyze full-length, first
      strand cDNA molecules with a much higher resolution than Northern blot analysis
      of mRNA molecules. This method can therefore be used to discriminate between the
      multiple mRNA species transcribed from a given gene or the homologous mRNA
      species transcribed from a given gene family.

PMID- 9187763
TI  - Use of manganese in RT-PCR eliminates PCR artifacts resulting from DNase I
      digestion.
AB  - The precise quantification of rare mRNA copies from intronless genes by reverse
      transcription polymerase chain reaction (RT-PCR) requires the complete removal of
      genomic DNA because discrimination of cDNA and DNA amplification products by
      differing sizes of PCR products is not possible. Elimination of DNA is achieved
      by treating the RNA sample with RNase-free DNase I before RT-PCR. The lack of a
      PCR product from DNase-treated RNA samples before RT is usually accepted as a
      proof of efficient DNA destruction. However, this may vary depending on the metal
      cofactor used in the DNase I cleavage. Treating DNA-contaminated RNA samples with
      DNase I and magnesium as a cofactor creates a negative PCR control after
      digestion without further RT. Paradoxically, after additional RT-PCR, the
      original intron-containing DNA fragment size may be produced again. In the
      presence of manganese as cofactor, RT-created DNA fragments do not appear. This
      is because in the presence of manganese, DNase I cleaves both DNA strands at
      approximately the same site, yielding DNA fragments that are blunt-ended or that
      have protruding termini of only one or two nucleotides in length. However,
      overlapping fragments with the potential to recombine are created by DNase
      digestion with magnesium as cofactor. Because one cannot differentiate between a
      PCR signal produced by RNA and one produced by recombined DNA after DNase I
      digestion and RT, all such DNase I assays should be performed with manganese
      instead of magnesium.

PMID- 9187764
TI  - Cassette for the generation of sequential gene disruptions in the yeast
      Schizosaccharomyces pombe.
AB  - The ability to conveniently construct gene disruptions is an important
      methodology for genetic analysis of the fission yeast Schizosaccharomyces pombe.
      Because of the limited number of selectable markers available for generating gene
      disruptions in fission yeast, the construction of strains that contain multiple
      gene disruptions can be quite difficult. This becomes a particular problem when
      episomal plasmids carrying selectable markers are also required within the same
      strains. To alleviate these difficulties, we have constructed a hisG-ura(4+)-hisG
      cassette that can be used repeatedly for constructing gene disruptions in S.
      pombe. This cassette allows the recycling of the ura4+ marker, thereby permitting
      the disruption of an indefinite number of genes sequentially within the same
      strain and/or for subsequently introducing a ura(4+)-marked plasmid.

PMID- 9187765
TI  - Double-labeled fluorescent probes for 5' nuclease assays: purification and
      performance evaluation.
AB  - An inexpensive method for the purification and evaluation of user-synthesized or
      crude commercially prepared double-labeled fluorescent probes is presented. These
      probes exhibit the characteristics required for use in 5'-nuclease assays,
      including efficient reporter dye quenching, target specificity and susceptibility
      to cleavage by Taq DNA polymerase during PCR amplification. The method is
      suitable for research laboratories that wish to develop 5' nuclease assays for
      the detection of PCR-amplified target sequences to eliminate the requirement for
      agarose gels and to advance throughput.

PMID- 9187766
TI  - Computer-assisted, quantitative cytokine enzyme-linked immunospot analysis of
      human immune effector cell function.
AB  - Originally developed for detecting antibody production from B lymphocytes, the
      enzyme-linked immunospot (ELISPOT) assay was later modified to assess cytokine
      production from various immune effector cells. Although the ELISPOT assay can
      detect antibody or cytokine production at the single-cell level, the visual
      counting of spots in a 96-well plate under a microscope makes this method
      unsuitable for handling large sample sizes. Here, we introduce a computer
      assisted image analysis system to overcome this problem. This system makes the
      data analysis step of the ELISPOT assay convenient, objective, sensitive and
      suitable for handling large sample pools. Studies requiring lymphocyte
      proliferation assay, cytotoxic lymphocyte assay and precursor frequency assay can
      be conducted through the ELISPOT assay. This is demonstrated here using examples
      such as mixed lymphocyte allogeneic reactions and human immunodeficiency virus
      antigen-specific, cell-mediated immune responses.

PMID- 9187767
TI  - Quantitative densitometric analysis using a commercially available handheld CCD
      digital camera.
AB  - We describe here a novel method that relies on a digital imaging device to
      perform densitometric quantitation of radiographs in the laboratory setting.
      Using fluorescent back-illumination and appropriate exposure settings, a
      commercially available handheld charge-coupled device (CCD) digital camera is
      used to acquire the image of the radiograph. Following acquisition, the image is
      downloaded by means of a serial interface to a personal computer. There, it is
      analyzed to ensure that the series of pixel intensities lie within the linear
      range and then quantitated using two-dimensional integration with local
      background substraction. Using a linear dot blot established with serial dilution
      of 32P and imaging with standard radiographic film, we found that images acquired
      using the handheld digital camera were comparable to those input with a desktop
      scanner in transmittance mode. Quantitative densitometric analysis showed similar
      linear results between the digital camera and the desktop scanner over the 16
      fold linear response of the radiographic film, both of which were comparable to
      phosphor imaging over that limited range. These findings demonstrate that the
      ever-improving technology of handheld digital imaging should be added to the
      repertoire of techniques for quantitative densitometry.

PMID- 9187768
TI  - Control of a remote microscope over the Internet.
AB  - Globally connected research sites frequently find the need to share information
      on a timely basis. The sharing of data obtained from microscopy has historically
      required that the researcher take micrographs of the desired image and send the
      film to the other site or, more recently, scan the micrographs into a computer
      and send the micrographs through e-mail. The authors identified the need to
      control and view, in as close to real time as possible, images being viewed on a
      remote microscope. The goal was to develop a system that would be versatile, easy
      to learn and readily adapted from existing materials and that would allow several
      users to simultaneously view and control the microscope. The use of commercially
      available materials along with a simple, custom-designed slide holder allowed
      researchers at remote sites to view one of 15 slides and move the slide as
      needed. The penalty for use of the Internet vs. dedicated phone lines such as
      Integrated Services Digital Network (ISDN) is that only 1 frame/7 s can be viewed
      at video resolution. The advantages of cost and multiple, simultaneous use over a
      ubiquitous system outweigh the disadvantage for most users.

PMID- 9187769
TI  - Computer program for calculating the melting temperature of degenerate
      oligonucleotides used in PCR or hybridization.
AB  - Degenerate primers or probes have been widely used in molecular cloning, but the
      calculation of their melting temperatures could not simply be done using
      thermodynamic parameters because of degeneracy and the lack of a computer
      program. We present here a simple computer program named dPrimer for the
      calculation of melting temperature of degenerate oligonucleotides based on the
      nearest-neighbor model. The program was written in C+2 computer language and
      implemented in Macintosh with a Symantec C+2 compiler. The degenerate sequencing
      data were read into a graph data structure. All possible oligonucleotide
      sequences were then determined by a depth-first search algorithm. Their melting
      temperature (Tm) values were individually calculated, and output was given as Tm
      range, mean and standard deviation. These data could help one in the selection of
      PCR annealing and hybridization temperatures as well as in the design of
      degenerate oligonucleotides with a desired range of Tm.

PMID- 9187770
TI  - Rescuing corrupted gel files from Model 377 and 373 DNA Sequencers.
AB  - Automated DNA sequencing requires the intensive use of computers to handle the
      large amount of data taken. When a computer failure occurs and the data are no
      longer accessible, all the expense and effort that went into the sequencing
      experiment is lost. By using the data storage architecture of Macintosh computers
      to our advantage, we may prevent this loss in the case of automatic sequencers
      from PE Applied Biosystems. The software required to allow the experimenter to do
      this has been written and is available free of charge.

PMID- 9187771
TI  - Visual Genome Explorer: a comparative visual interface to genome data.
AB  - In response to the deluge of genome data, we are developing Visual Genome
      Explorer, an interactive graphical interface to genome data. Given is a
      description of the prototype program, which introduces the concept of visual
      comparative genomics for complete bacterial genomes.

PMID- 9187772
TI  - Application of oligonucleotide activation to restriction endonuclease NarI.
AB  - Restriction endonuclease NarI cleaves DNA using a two-site mechanism, placing it
      in the Type IIe class of restriction endonucleases. Although these enzymes have
      very useful recognition sequences, the two-site mechanism limits the practical
      application. Site preferences often cause incomplete substrate digestion.
      Oligonucleotide activation of NarI eliminates incomplete digestions, making it
      possible to use NarI restriction sites in many common molecular biology
      techniques. A modified oligonucleotide was chosen for optimal activation of
      restriction endonuclease NarI. This oligonucleotide was demonstrated to allow
      complete digestion in many commonly used substrates.

PMID- 9187773
TI  - Measurement of nucleic acid concentrations using the DyNA Quant and the
      GeneQuant.
AB  - Molecular biology is now a routine tool in almost all biological research fields.
      With the exponential growth in the number of molecular biological techniques,
      there is a recognizable need for sensitive, accurate and precise quantitation of
      nucleic acids. We present here two complementary instruments designed for the
      quantitation of nucleic acids, the GeneQuant II and the DyNA Quant 200
      Fluorometer. The GeneQuant II can rapidly determine the UV absorbance of a
      solution and display the calculated DNA, RNA or protein concentration. In
      addition, the GeneQuant can display calculated melting temperatures for a given
      DNA oligonucleotide base sequence, a useful feature for primer design. The DyNA
      Quant 200 quantitates DNA on the basis of the fluorescent Hoechst 33258
      dye/double-stranded (ds)DNA assay. Upon binding to dsDNA, the spectral properties
      of the dye change such that it becomes highly fluorescent at 460 nm when excited
      at 365 nm. The assay has proven to be a specific and sensitive alternative method
      for DNA quantitation, particularly for unpurified DNA samples. Together, the
      GeneQuant II and the DyNA Quant 200 are a cost-effective and convenient solution
      to the routine protein and nucleic acid quantification needs of the molecular
      biologist.

PMID- 9187774
TI  - The characteristics of excellent clinical teachers.

PMID- 9187775
TI  - Local anaesthetics belong in the caudal/epidural space, not in the veins!

PMID- 9187776
TI  - Characteristics of good anaesthesia teachers.
AB  - PURPOSE: The Department of Anaesthesia undertook a qualitative study to a) reveal
      the characteristics of teachers who had been identified as "good," and b) explore
      the levels of epistemological development (defined as conceptualization of
      knowledge) that are evidenced. Changes in medical education curricula have
      focused attention on the ways in which medical teaching staff conceptualize the
      learning/teaching interactions and their ability to alter or modify their
      teaching styles. Teachers are often assessed or informally recognized as "good
      teachers," but there are few indicators to guide what is meant by the label in
      anaesthesia. METHODS: Teachers who had consistently received overall ratings of
      4+ on a 5 point rating scale over a five year period were selected to be
      interviewed. Data were analyzed a) noting key teaching characteristics and
      patterns of teaching and b) within the framework of adult development theories.
      RESULTS: Good teachers in Anaesthesia all identified six characteristics
      necessary for good teaching. They were characterised by their "inquiry" approach
      to teaching, their complexity of thought and their functioning at higher
      relativistic/Commitment levels of epistemological development. CONCLUSION:
      Teaching in anaesthesia is depicted by the need to address multiple aspects of
      thinking and action. Good teachers are aware of these aspects and include
      techniques that offer residents opportunities to develop their thinking skills to
      deal with medical complexities as well as guiding learners to increase their
      knowledge. The interviewed teachers' revealed approaches to teaching and learning
      that indicated their own personal cognitive complexity and levels of development.

PMID- 9187777
TI  - Detection of intravascular injection of regional anaesthetics in children.
AB  - PURPOSE: Detection of intravascular injection of local anaesthetic during
      placement of regional blocks in children by using epinephrine-induced tachycardia
      or hypertension may produce false positive and false negative findings. This
      study evaluates ECG changes as markers of intravascular injection of local
      anaesthetics with epinephrine, during placement of epidural blocks in children.
      METHODS: Observational study in a teaching hospital of all epidural anaesthetics
      administered to paediatric patients during one year. General anaesthesia, where
      used, was not controlled. An ECG rhythm strip was recorded during test dose
      injection and analyzed for changes in rate, rhythm, and T-wave configuration.
      RESULTS: During the study period, 742 paediatric epidural blocks were
      administered. There were 644 caudal (284 without catheters), 97 lumbar, and one
      thoracic epidural anaesthetics. Satisfactory placement was achieved in 97.7% of
      patients. Intravascular injection was detected in 42 (5.6%) of epidural
      anaesthetics (3.8% and 6.7% of straight needle and catheter injections,
      respectively). Detection was by immediate aspiration of blood in six patients,
      and by heart rate increases > 10 bpm in 30. Five had heart rate decreases
      suggesting a baroreceptor response. Five had heart rate increases < 10 bpm that
      were possible responses to noxious stimuli. Of 30 patients with known
      intravascular injection and for whom ECG strips were available, 25 (83%) had T
      wave amplitude increases > 25%, and 29 (97%) had ECG changes in T-wave or rhythm
      in response to the epinephrine injection. There were no false positives.
      CONCLUSION: In order to reduce risks associated with epidural anaesthesia in
      children, epinephrine should be added to the local anaesthetic test dose, the ECG
      should be monitored continuously for changes in heart rate, rhythm, and T-wave
      amplitude. Epidural injections should be given in small increments.

PMID- 9187778
TI  - Double-blind comparison of epidural ropivacaine 0.25% and bupivacaine 0.25%, for
      the relief of childbirth pain.
AB  - PURPOSE: To evaluate the efficacy of ropivacaine 0.25% when administered
      epidurally for relief of labour pain and to compare it with bupivacaine 0.25%.
      METHODS: In a multicentre investigation, 60 ASA I and II labouring women were
      randomized in a double-blind fashion to receive either bupivacaine 0.25% or
      ropivacaine 0.25% administered epidurally by intermittent top-up for labour
      analgesia. Using a standardized technique, epidural analgesia was initiated after
      the woman received 10-15 ml-kg.1 crystalloid solution. Maternal blood pressure,
      heart rate, analgesia sensory level, degree of motor block and visual analogue
      pain scores were measured by the research nurse prior to, and at regular
      intervals, following the administration of analgesia. Total dose of local
      anaesthetic administered, duration of labour, mode of delivery, and maternal and
      fetal/neonatal side effects were noted. The fetus/neonate was assessed by the
      research nurse using the fetal heart rate tracing, Apgar scores at delivery and
      neonatal neurobehavioural assessments at 2 and 24 hr postnatally. Maternal and
      investigators' satisfaction with the analgesia achieved was assessed after
      delivery. RESULTS: No differences were found between the two agents in any of the
      variables studied. CONCLUSION: Ropivacaine 0.25%, when administered epidurally by
      intermittent top-ups for labour analgesia, was equally efficacious as bupivacaine
      0.25%.

PMID- 9187779
TI  - Labour analgesia with intrathecal fentanyl decreases maternal stress.
AB  - PURPOSE: Lumbar epidural analgesia (LEA) decreases maternal stress as measured by
      maternal circulating plasma catecholamine concentrations. Intrathecal fentanyl
      (ITF) provides effective labour analgesia but its effect on maternal epinephrine
      (Epi) and norepinephrine (NE) concentrations is not known. This study assesses
      whether ITF reduces maternal stress in the same manner as conventional LEA.
      METHODS: Twenty-four healthy women in active labour received either 25 micrograms
      ITF (n = 12) or epidural lidocaine 1.5% (n = 12) for analgesia. Venous blood
      samples were collected before anaesthesia and at five minute intervals for 30 min
      following anaesthesia for the measurement of plasma Epi and NE by high
      performance liquid chromatography. Maternal blood pressure (BP), heart rate (HR),
      visual analog scores (VAS) to pain and pruritus were recorded at the same time.
      RESULTS: Both ITF and LEA decreased pain VAS scores, maternal BP, and plasma Epi
      concentrations with only minimal effects on plasma NE concentrations. Intrathecal
      fentanyl (ITF) and LEA reduced plasma epi to a similar extent, with ITF reducing
      the levels slightly faster than LEA. Intrathecal fentanyl(ITF) and LEA reduced
      plasma Epi concentrations by 52% and 51%, respectively (P value < 0.01).
      CONCLUSION: We conclude that ITF is as effective as LEA in producing pain relief
      in the labouring patient. Intrathecal Fentanyl (ITF) is also capable of reducing
      maternal plasma epinephrine concentration, thus avoiding the possibly deleterious
      side effects of excess amounts of this catecholamine during labour.

PMID- 9187780
TI  - Histamine release during cardiopulmonary bypass in neonates and infants.
AB  - PURPOSE: Histamine release has been previously documented in adults and children
      during cardiopulmonary bypass (CPB). It has not been studied in neonates nor
      during deep hypothermic circulatory arrest (DHCA). Histamine effects could
      explain many perioperative complications of congenital cardiac surgery such as
      dysrhythmias and massive oedema. Therefore, documentation of histamine release in
      the perioperative period is of clinical importance. The source of histamine can
      be determined by measurement of tryptase which is released with histamine from
      mast cells but not basophils. METHODS: Blood samples for histamine and tryptase
      were taken before and after specific events eg. cross-clamp removal, during
      anaesthesia and CPB in 14 infants and seven neonates undergoing complex
      congenital heart repairs and were analysed by commercial radioimmunoassays.
      Haemodynamic variables and pre and post-op weights were recorded to look for
      correlation between pathophysiological events and histamine release. RESULTS:
      Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng.ml-1 at
      five minutes, (P < .005). There were no changes associated with DHCA and a small
      rise with reventilation (P < 0.02). Histamine concentration was lower in neonates
      than in infants (P < 0.05) during CPB. Plasma histamine and tryptase
      concentrations did not correlate, suggesting histamine release was from basophils
      and not from mast cells. Haemodynamic variables did not correlate with histamine
      concentrations. CONCLUSION: There was no major histamine release during CPB in
      infants and neonates. There was no relationship between histamine concentrations
      and clinical variables. Histamine released during CPB appears to come from
      basophils and may be a function of age.

PMID- 9187781
TI  - Enhanced spontaneous antibody response after coronary artery bypass surgery.
AB  - PURPOSE: Cells spontaneously secreting immunoglobulins can be seen in the blood
      one week after open-heart surgery. The purpose of this study was to measure the
      antibody specificities of activated cells. METHODS: Immune responses were studied
      preoperatively and on the seventh postoperative day in 18 patients undergoing
      elective coronary artery bypass surgery. The number of cells secreting
      adenovirus, measles, rubella and tetanus antigen specific antibodies
      spontaneously and induced by pokeweed mitogen PWM (ASCs) as well as the total
      number of cells secreting IgG, IgM and IgA (ISCs) were studied using an enzyme
      linked immunospot (ELISPOT) assay. Spontaneous as well as phytohaemagglutinin
      (PHA)- and pokeweed mitogen (PWM)-induced lymphocyte proliferation was also
      measured. RESULTS: The number of cells spontaneously secreting IgG, IgM and IgA
      antibodies was increased on the seventh day after coronary bypass surgery,
      against adenovirus, measles, rubella and tetanus as well as the total number of
      cells secreting immunoglobulins IgG, IgM and IgA (P < 0.05/0.001). By contrast,
      only slight fluctuation was seen in the numbers of cells secreting antibodies
      after PWM stimulation. Spontaneous lymphocyte proliferation was also increased,
      PHA proliferative responses were depressed and PWM responses were not changed on
      the seventh postoperative day compared with preoperative values. CONCLUSION:
      Coronary artery bypass surgery caused marked polyclonal B cell activation
      demonstrated by an increase of cells producing spontaneously antibodies against
      virus antigens and tetanus toxoid. This activation could not be intensified by
      PWM stimulation.

PMID- 9187782
TI  - Cardiac performance during unilateral lumbar spinal block after crystalloid
      preload.
AB  - PURPOSE: The haemodynamic effects of crystalloid preload were evaluated in a
      randomised blind study in 20 ASA status I-II, 50-80 yr-old patients, undergoing
      unilateral spinal anaesthesia for leg surgery produced with low doses of
      hyperbaric bupivacaine. METHODS: Baseline non-invasive blood pressure
      (oscillometry), heart rate, stroke volume and cardiac index (transthoracic
      electrical bioimpedance) were recorded. Then, patients were randomly allocated to
      receive 10 ml.kg-1 Ringer's Lactate solution over 20 min (preload group, n = 10)
      or no crystalloid infusion (no-preload group, n = 10). Spinal block was performed
      using 8 mg hyperbaric bupivacaine 0.5% injected slowly at the L2-L3 interspace
      (0.02 ml.sec-1 through a 25-gauge Whitacre needle) with patients lying on their
      operated side and with the needle opening directed towards the dependent side.
      Lateral decubitus position was maintained for up to 15 min after anaesthetic
      injection to facilitate hyperbaric bupivacaine distribution towards dependent
      regions of the subarachnoid space. Haemodynamic variables were recorded 5, 10, 15
      and 30 min after spinal injection, while sensory level and motor block were
      evaluated 10, 15 and 30 min after anaesthetic injection on both operated and
      unoperated side. RESULTS: No differences of upper sensory level and motor block
      were observed between the two groups on the operated and non-operated sides.
      Diastolic blood pressure was decreased compared with baseline in the no-preload
      group only (P = .0001). Systolic arterial pressure and heart rate did not change
      in either group. Stroke volume and cardiac index were decreased in the no-preload
      group compared with both baseline (P = .02; P = .001) and the preload group (P =
      .04; P = .02). CONCLUSION: Crystalloid preload influences cardiovascular function
      during spinal block, and may be useful when very low bupivacaine doses and
      lateral decubitus are used to achieve unilateral spinal block.

PMID- 9187783
TI  - Propofol or midazolam for sedation and early extubation following cardiac
      surgery.
AB  - PURPOSE: The purpose of this randomized, double-blind study was to evaluate the
      efficacy of midazolam and propofol for postoperative sedation and early
      extubation following cardiac surgery. METHODS: ASA physical status II-III
      patients scheduled to undergo elective first-time cardiac surgery with an
      ejection fraction > 45% were eligible. All patients received a standardized
      sufentanil/isoflurane anaesthesia. During cardiopulmonary bypass 100
      micrograms.kg-1.min-1 propofol was substituted for isoflurane. Upon arrival in
      the Intensive Care Unit (ICU), patients were randomized to either 10
      micrograms.kg-1.min-1 propofol (n = 21) or 0.25 microgram.kg-1.min-1 midazolam (n
      = 20). Infusion rates were adjusted to maintain sedation within a predetermined
      range (Ramsay 2-4). The infusion was terminated after four hours. Patients were
      weaned from mechanical ventilation and their tracheas extubated when Haemodynamic
      stability, haemostasis, normothermia and mental orientation were confirmed.
      Haemodynamic measurements, arterial blood gas tensions and pulmonary function
      tests were recorded at specified times. RESULTS: There were no differences
      between the two groups for the time spent at each level of sedation, number of
      infusion rate adjustments, amount of analgesic and vasoactive drugs, times to
      awakening and extubation. The costs of propofol were higher than those of
      midazolam. There were no differences in haemodynamic values, arterial blood gas
      tensions and pulmonary function. CONCLUSION: We conclude that midazolam and
      propofol are safe and effective sedative agents permitting early extubation in
      this selected cardiac patient population but propofol costs were higher.

PMID- 9187785
TI  - Low and minimal flow inhalational anaesthesia.
AB  - PURPOSE: To describe the pharmacokinetic behaviour and practical aspects of low
      (0.5-1 l.min-1) and minimal (0.25-0.5 l.min-1) flow anaesthesia. METHODS: A
      Medline search located articles on low flow anaesthesia, and computer simulated
      anaesthetic uptake models are used. PRINCIPAL FINDINGS: Most, 85-90%, of
      anaesthetists use high fresh gas flow rates during inhalational anaesthesia.
      Low/minimal flow anaesthesia with a circle circuit may avoid the need for in
      circuit humidifiers, raise the temperature of inspired gases by up to 6 degrees
      C, reduce cost by about 25% by reduction of fresh gas flows to 1.5 l.min-1, and
      reduce environmental pollution with scavenged gas. Knowledge of volatile
      anaesthetic pharmacokinetic behaviour facilitates the use of minimal/low flow
      rates. Small amounts of nitrogen or minute amounts of methane, acetone, carbon
      monoxide, and inert gases in the circuit are of no concern, but the degradation
      of desflurane (to carbon monoxide by dry absorbent) and sevoflurane (to compound
      A by using a fresh gas flow of > 2 l.min-1) must be avoided. With modern gas
      monitoring technology, safety should be no more of a concern than with high flow
      techniques. CONCLUSION: The use of fresh gas flow rates of < 1 l.min-1 for
      maintenance of anaesthesia has many advantages, and should be encouraged for
      inhalational anaesthesia with most modern volatile anaesthetics.

PMID- 9187784
TI  - Clonidine decreases vasoconstriction and shivering thresholds, without affecting
      the sweating threshold.
AB  - PURPOSE: This study was conducted to test the hypothesis that clonidine produces
      a dose-dependent increase in the sweating threshold and dose-dependent decreases
      in vasoconstriction and shivering thresholds. METHODS: Six healthy subjects (two
      female) were studied on four days after taking clonidine in oral doses of either
      0 (control), 3, 6 or 9 micrograms.kg-1. The order followed a balanced design in a
      double-blind fashion. Oesophageal temperature and mean skin temperature (from 12
      sites) were measured. Subjects were seated in 37 degrees C water which was
      gradually warmed until sweating occurred (sweat rate increased above 50 g.m-2.h
      1). The water was then cooled gradually until thresholds for vasoconstriction
      (onset of sustained decrease in fingertip blood flow) and shivering (sustained
      elevation in metabolism) were determined. Thresholds were then referred to as the
      core temperature, adjusted to a designated mean skin temperature of 33 degrees C.
      RESULTS: High dose clonidine similarly decreased the adjusted core temperature
      thresholds for vasoconstriction by 1.16 +/- 0.30 degrees C and for shivering by
      1.63 +/- 0.23 degrees C (P < 0.01). The dose response effects were linear for
      both cold responses with vasoconstriction and shivering thresholds decreasing by
      0.13 +/- 0.05 and 0.19 +/- 0.09 degree C.microgram-1 respectively (P < 0.0001).
      The sweating threshold was unaffected by clonidine, however the interthreshold
      range between sweating and vasoconstriction thresholds increased from control
      (0.19 +/- 0.48 degree C) to high dose clonidine (1.31 +/- 0.54 degrees C).
      CONCLUSION: The decreases in core temperature thresholds for cold responses and
      increased interthreshold range are consistent with the effects of several
      anaesthetic agents and opioids and is indicative of central thermoregulatory
      inhibition.

PMID- 9187786
TI  - Anaesthesia for phaeochromocytoma in pregnancy.
AB  - PURPOSE: Phaeochromocytoma in pregnancy is a rare occurrence. Details of the
      anaesthetic are even more rarely reported. Our purpose is to describe our
      management with reference to previous reports. CLINICAL FEATURES: A 31-yr-old
      woman underwent resection of a phaeochromocytoma at seven weeks gestation.
      Preoperative preparation included 2 mg prazosin p.o. bid and 40 mg propranolol
      p.o. bid. A balanced anaesthetic technique including 5 mg midazolam, 1500
      micrograms alfentanil, 35 micrograms sufentanil, nitrous oxide and isoflurane was
      used. Blood pressure was controlled with 3.4 g magnesium and 2437 micrograms
      nitroglycerin. There were no episodes of hypertension intraoperatively. The
      patient made an uneventful recovery and delivered a normal baby at 37 wk
      gestation by caesarean section. CONCLUSION: Anaesthesia for resection of a
      phaeochromocytoma in early pregnancy can be successfully managed with
      preoperative alpha and beta sympathetic blockade and a balanced anaesthetic
      technique using magnesium as the main intraoperative hypotensive agent.

PMID- 9187787
TI  - Difficult intubation and brain-stem anaesthesia.
AB  - PURPOSE: To present a case of difficult intubation with brainstem anaesthesia
      after retrobulbar block with bupivacaine and lidocaine and sedation with
      midazolam and to point out that close monitoring and timely treatment is
      important in preventing an unfavourable outcome. CLINICAL FEATURES: An 82-yr-old
      man with treated hypertension and stable angina was scheduled for cataract
      extraction. Physical examination revealed a class 2 airway. He had a retrobulbar
      block after topical tetracaine drops, with bupivacaine 0.5% and lidocaine 2% with
      hyaluronidase under sedation with 1 mg midazolam. Five minutes after the block,
      respiration slowed, he became unresponsive and oxygen saturation decreased to
      80%. Immediate ventilation with mask without additional oxygen improved
      saturation. Attempted tracheal intubation failed: the epiglottis could not be
      visualized despite flaccid jaw and extremities. A laryngeal mask airway was
      placed which was leaking and adequate ventilation could not be achieved but a
      second laryngeal mask airway was placed successfully. CONCLUSION: This case
      emphasizes the need for dose monitoring and personnel capable of managing the
      difficult airway when intra-orbital anaesthesia is used.

PMID- 9187788
TI  - Hyperthermia after cardiac surgery.
AB  - PURPOSE: To describe two cases of hyperthermia occurring after cardiac surgery.
      CLINICAL FEATURES: At the end of cardiopulmonary bypass, protamine was injected
      to reverse heparin. Following protamine, hypotension, pulmonary hypertension and
      hypoxia developed, but protamine induced hypotension recovered after
      administration of methyl predonisolone and catecholamines. Rectal temperature
      increased to 41 degrees C in the first case and 40 degrees C in the second after
      recovery from protamine induced hypotension. Arterial blood gas analysis,
      breathing 100% oxygen, showed severe acidosis and hypercapnia (pH 6.96, PaCO2 73
      mmHg, PaO2 45 mmHg. BE -18 in the first case, and pH 7.13, PaCO2 59.9, PaO2 52.8,
      BE -11 in the second). At the same time, creatine phosphokinase levels showed
      8400 u.L-1 in the first case and 4369 u.L-1 in the second. Serum and urine
      myoglobin concentrations were 334.2 ng.ml-1 and 1085 ng.ml-1, and 468 ng.ml-1 and
      885 ng.ml-1, respectively. Efforts to cool the patients using alcohol were made.
      Following dantrolene (400 mg and 200 mg), the hyperthermia, acidosis, hypoxaemia
      and hypercarbia subsided (temperature 37.5 and 37.5 degrees C, PaO2 220 mmHg and
      180 mmHg with 100% oxygen, PaCO2 35 mmHg and 41 mmHg respectively).
      Postoperatively, 20 mg.hr-1 dantrolene infusion were administered for 24 hr. In
      the first case, an anaphylactoid reaction was confirmed by increased plasma
      tryptase. CONCLUSION: We report two cases of hyperthermia after cardiac surgery
      in whom dantrolene was very effective in reducing the high rectal temperature.

PMID- 9187789
TI  - Epidural anaesthesia for ureteral reimplantation in an infant with congenital
      tracheal stenosis.
AB  - PURPOSE: We report a case of an infant with severe congenital tracheal stenosis
      who underwent ureteral reimplantation using lumbar epidural anaesthesia combined
      with light general anaesthesia. CLINICAL FEATURES: A six-month-old girl with
      symptomatic tracheal stenosis, demonstrated by computed tomography, was scheduled
      for ureteral reimplantation. She received continuous lumbar epidural anaesthesia
      with bupivacaine 0.25% through a 21 gauge catheter positioned at L3-4 interspace.
      Nitrous oxide/oxygen 50% and sevoflurane 1.5-2% were administered through a face
      mask and spontaneous breathing was preserved. Anaesthesia and surgery were
      uneventful. Postoperative epidural analgesia with bupivacaine 0.2% was excellent.
      The epidural catheter was withdrawn 48 hr postoperatively and she was discharged
      from the hospital five days later. CONCLUSION: Airway management is a major
      anaesthetic consideration in an infant with tracheal stenoses requiring abdominal
      surgery. We have demonstrated that regional anaesthesia combined with light
      general anaesthesia via face mask is an acceptable option, providing good
      analgesia during and after surgery. The technique preserves spontaneous
      ventilation and avoids tracheal manipulation.

PMID- 9187790
TI  - Heat conservation vs convective warming in adults undergoing elective surgery.
AB  - PURPOSE: To determine the relative efficacy of heat conservation and convective
      warming in maintaining perioperative normothermia, (central temperature > or = 36
      degrees C). METHODS: Thirty-seven patients undergoing elective gynaecological,
      orthopaedic, or general surgery scheduled to last two hours were prospectively
      studied. Patients were randomized to one of two groups. Group 1 patients received
      heat conservation with reflective blankets (Thermadrape, Vital Signs, Inc.,
      Totowa, NJ) applied preoperatively and warmed i.v. fluids (Hotline SIMS Level I
      Technologies, Inc, Rockland, MA), Group 2 patients received convective warming
      (BairHugger, Augustine Medical Inc., Eden Prairie, MN) after induction of
      anaesthesia and i.v. fluids at room temperature. All patients received general
      anaesthesia with isoflurane. Tympanic membrane and forearm-fingertip skin
      temperature gradients were measured perioperatively at 15 min intervals. RESULTS:
      Central temperature decreased after induction to a minimum level of 35.9 +/- 0.1
      degrees C in group 1 and 36.0 +/- 0.1 degrees C in group 2 and then increased
      towards pre-induction values in group 2, and were higher (P < 0.05) than in group
      1: 95% group 2 patients had central temperature > or = 36.0 degrees C at the end
      of surgery (vs 69% of group 1, P < 0.05). During the first 30 min in PACU,
      central temperatures were higher in group 1 than in group 2 (36.8 +/- 0.1 degrees
      C vs 36.2 +/- 0.2 degrees C, P < 0.05). After 60 min, central temperatures were
      similar (36.8 degrees C). The incidence of shivering and degree of peripheral
      cutaneous vasoconstriction were also similar. CONCLUSION: Patients receiving
      convective warming were more likely to leave the operating room normothermic, and
      had higher central temperatures during the first 30 min in the recovery room. The
      intergroup temperature differences were small, and by 60 min, had disappeared.

PMID- 9187791
TI  - The McCoy levering laryngoscope in patients with limited neck extension.
AB  - PURPOSE: The McCoy levering laryngoscope is a modified Macintosh laryngoscope,
      which has a hinged tip controlled by a lever on the handle. The purpose of this
      study was to investigate whether the tip elevation of this laryngoscope results
      in better laryngeal visualization than using the Macintosh laryngoscope when the
      patient's neck is fixed in the neutral position. METHODS: Fifty female patients
      (ASA physical status I-II) undergoing elective surgery during general anaesthesia
      were investigated. The patient's neck was manually fixed in the neutral position
      by an assistant, and laryngeal visualization was attempted first with a size #3
      Macintosh laryngoscope (Macintosh trial), and then with a size #3 McCoy levering
      laryngoscope with blade tip elevation (McCoy trial), and tracheal intubation was
      attempted. Trials of laryngeal visualization were evaluated with the Cormack
      score. RESULTS: In the Macintosh trial, 36 of 50 (72%) patients were evaluated
      grade 3, and two grade 4. In most of the patients graded 2 and 3 in the Macintosh
      trial (70% of the grade 2 and 83% of the grade 3 cases), the laryngeal view was
      improved by using the McCoy levering laryngoscope. The Cormack grade in the McCoy
      trial was less than that in the Macintosh trial (P < 0.01). No complications were
      observed during the study. CONCLUSION: The McCoy levering laryngoscope improved
      laryngeal visualization in patients whose neck cannot be extended.

PMID- 9187792
TI  - Mild hypothermia therapy after cardiopulmonary resuscitation may improve cerebral
      resuscitation.

PMID- 9187793
TI  - Aging and cardiovascular autonomic regulation.

PMID- 9187794
TI  - Bilateral compartment syndrome following prolonged anaesthesia in the lithotomy
      position.

PMID- 9187796
TI  - Do the opioids have an antibacterial effect?

PMID- 9187795
TI  - Watch your surgeon.

PMID- 9187797
TI  - A case of blunt neck trauma with adverse posture for emergency awake
      tracheostomy.

PMID- 9187798
TI  - The Canadian Food Inspection Agency.

PMID- 9187799
TI  - Are we veterinarians a pain in the butt?

PMID- 9187800
TI  - An ethicist's commentary on the case of the veterinarian who wishes to improve
      rural euthanasia.

PMID- 9187801
TI  - Competency or incompetency--the dilemma.

PMID- 9187803
TI  - Metastatic vaccine associated fibrosarcoma in a 10-year-old cat.

PMID- 9187804
TI  - Varices with thrombosis in the cervix and uterus of a mare.
AB  - Cervical and uterine varices with thrombosis were observed at the necropsy of a
      virgin 16-year-old Peruvian Paso that had previous episodes of hemorrhage from
      the uterus. Practitioners and pathologists should be alert to the possibility of
      ruptured varices in mares with hemorrhage into the uterus or from the vulva.

PMID- 9187802
TI  - Chronic hepatitis: a retrospective study in 34 dogs.
AB  - The aims of this study were to characterize the histological changes observed in
      34 accessioned cases of canine chronic hepatitis and to correlate these changes
      with the clinical pathological data. Cases of chronic hepatitis were subdivided
      into 6 categories: chronic active hepatitis (10/34), chronic persistent hepatitis
      (7/32), chronic cholestatic hepatitis (6/34), fibrosing hepatitis with cirrhosis
      (3/34), chronic cholangiohepatitis (3/34), and miscellaneous secondary hepatitis
      (5/34). Iron accumulation was a consistent finding in all livers examined.
      Although all cases of chronic hepatitis had elevated liver enzymes, no
      correlation was detected between biochemical parameters and the severity of
      morphologic changes. Similarly, no correlation was detected between rhodanine
      staining for copper and morphologic or biochemical indicators of cholestasis.
      However, presence of copper correlated well with reticulo-fibrosis (r = 0.8) and
      bile duct hyperplasia, suggesting that changes in the hemodynamics of the hepatic
      acini due to fibrosis could influence storage of copper.

PMID- 9187805
TI  - Anal leiomyoma in a Holstein heifer.
AB  - A 2-year-old heifer was presented with masses on her anus that were interfering
      with cervical manipulation during embryo flushing. The masses had broad stalks
      attached within the anal sphinchter. Recovery was without incident after surgical
      resection. No recurrence of the masses had occurred 3 months later. Histologic
      diagnosis was benign leiomyoma.

PMID- 9187806
TI  - Topical (pour-on) ivermectin in the treatment of canine scabies.
AB  - The efficacy of a pour-on formulation of ivermectin at 500 micrograms/kg body
      weight applied on the dorsum on days 1 and 15 was evaluated in 90 dogs from a
      shelter, naturally infested with Sarcoptes scabiei. This very practical form of
      treatment was successful in eradicating scabies from this shelter.

PMID- 9187808
TI  - Salmonella infection in wild birds from Quebec.

PMID- 9187807
TI  - Multicentric lymphosarcoma with ovarian involvement in a Nubian goat.
AB  - Multiple lymph node enlargement and an intra-abdominal mass were diagnosed in a 6
      year-old doe. Necropsy revealed lymphosarcoma involving multiple organs,
      including the ovaries. Lymphosarcoma is rare in goats; ovarian involvement has
      not previously been reported.

PMID- 9187809
TI  - Detection and characterization of porcine circovirus associated with postweaning
      multisystemic wasting syndrome in pigs.

PMID- 9187810
TI  - Protozoal dermatitis of farmed Atlantic salmon in British Columbia.

PMID- 9187811
TI  - Anesthesia for North American cervids.

PMID- 9187812
TI  - Diagnostic ophthalmology. Distichiasis and uveal cysts.

PMID- 9187813
TI  - Pulmonary rehabilitation and surgery for end-stage lung disease.
AB  - Pulmonary rehabilitation is a multidisciplinary approach to the comprehensive
      management of patients with end-stage lung disease. Components of the pulmonary
      rehabilitation program include education, exercise, nutrition, and psychosocial
      support. Most of the information published on pulmonary rehabilitation has been
      from patients with COPD. There are some data on patients with cystic fibrosis
      but, unfortunately, there is a lack of information on other causes of end-stage
      lung disease. Published data almost invariably show improvements in functional
      capacity (i.e., walk distance) and quality of life. There are no objective
      physiologic changes in lung function. Because patients who attend programs
      regularly are a carefully selected subpopulation, conclusions from published
      reports may not apply to all patients with end-stage lung disease. The
      recommendation for pulmonary rehabilitation prior to lung volume reduction
      surgery or lung transplantation is based on assumptions that may not necessarily
      be true. No data exist that conclusively show that preoperative rehabilitation
      alters outcome. Nevertheless, given the relatively benign nature of pulmonary
      rehabilitation and the documented benefits, it is reasonable to recommend such a
      program to patients who are awaiting surgical intervention. Further research is
      required to define the role, nature, duration, intensity, and frequency of
      exercise training in the management of patients who are to undergo surgical
      treatment for advanced lung disease.

PMID- 9187814
TI  - Patient selection, evaluation, and preoperative management for lung transplant
      candidates.
AB  - The selection process to assess candidacy for transplant is based on medical and
      psychosocial criteria and surgical considerations. The degree of disease severity
      requiring transplantation for survival has become more apparent as the disparity
      in survival outcome widens between patients with and without transplant. The
      contraindications to transplant surgery have been modified over time. Candidate
      selection is considered in the context of the risks and benefits of the surgical
      procedure on a case by case basis. The wait for transplant has increased as the
      growth in the number of candidates for transplant exceeds available donors. As
      much as 30% of patients die on the UNOS waiting list.

PMID- 9187815
TI  - Evaluation and preoperative management of lung volume reduction surgery
      candidates.
AB  - The efficacy of lung volume reduction surgery has been demonstrated by
      improvements in functional status, dyspnea, pulmonary function, alveolar gas
      exchange, and exercise tolerance. However, surgery has a significant morbidity,
      mortality, and cost. Surgical outcome is dependent on the clinical, anatomical,
      and physiological features of the patients and their emphysema. Therefore, the
      patient evaluation process and the preoperative optimization of medical therapy
      are crucial for success. Through understanding mechanisms for improvement have
      added insight to the selection process, patient selection needs further
      clarification.

PMID- 9187816
TI  - Indications. Unilateral, bilateral, heart-lung, and lobar transplant procedures.
AB  - Indications for unilateral, bilateral, heart-lung, and lobar transplant
      procedures for emphysema, cystic fibrosis, primary pulmonary hypertension, and
      pulmonary fibrosis are presented, and a brief historical perspective of the
      procedures is supplied.

PMID- 9187817
TI  - Donor criteria and evaluation.
AB  - Limited donor availability for organ transplantation has led to the progressive
      reevaluation and liberalization of donor acceptance criteria. This article
      discusses the existing and expanding criteria for the evaluation and use of
      donated organs for lung transplantation.

PMID- 9187818
TI  - Donor considerations in living-related donor lung transplantation.
AB  - Living donor lung transplantation has been performed in the United States since
      1990. Based on the experience in living donor kidney transplantation which began
      in 1954, and living donor liver transplantation which began in 1989, considerable
      progress has occurred in surgical technique, selection of recipients and donors,
      and the indications for and timing of the procedure. The vast majority of living
      donor lung transplantations have been performed in patients with cystic fibrosis.
      Early results concerning graft function, donor recovery, and recipient outcome
      are encouraging.

PMID- 9187819
TI  - Early and long-term functional outcomes in unilateral, bilateral, and living
      related transplant recipients.
AB  - Lung transplantation offers the possibility of improved quality of life and
      survival in patients with severe pulmonary and pulmonary vascular disease. Since
      the first human lung allotransplantation in 1963, survival has moved from hours
      or days into the present era of long-term (years) survival in many recipients.
      Measurement of outcome has now extended to measurement of exercise capacity and
      quality of life. A substantial improvement in quality of life is seen; however,
      exercise capacity remains moderately impaired in spite of the return (in many) of
      near normal cardiopulmonary function, suggesting peripheral limitation to
      exercise. Recently, fiber type changes and abnormal oxidative metabolism have
      been shown in the skeletal muscle of stable lung transplant recipients. This
      suggests a persistence of a pretransplant skeletal muscle injury and/ or the
      effects of post-transplant immunosuppression (particularly Cyclosporin A and
      corticosteroids).

PMID- 9187820
TI  - Early and long-term functional outcomes following lung volume reduction surgery.
AB  - In the past 3 years, lung volume reduction surgery has become the most
      controversial topic in the clinical management of patients with emphysema.
      Although literature has added to the understanding of the procedure, many
      important issues remain unclear. This article emphasizes functional and basic
      physiologic changes that occur following lung volume reduction surgery in
      patients with emphysema.

PMID- 9187821
TI  - Perioperative management in lung transplantation.
AB  - Despite the multitude of potential complications that may be encountered during
      the early post-transplant period, the majority of transplant recipients
      experience a smooth transition from postoperative intensive care, to step-down
      unit, to the regular medical floor, and, ultimately, to their home within 10 to
      14 days without any significant unexpected events. The likelihood of serious
      complications can be greatly reduced through careful recipient selection,
      impeccable donor management, and the cooperative efforts of surgeons,
      pulmonologists, nurse specialists, and the numerous experienced consultants
      required for a successful transplant program. Although many unique facets
      contribute to the complexity of lung transplant patient care, attention to the
      details of high-quality general postsurgical care will yield excellent results.

PMID- 9187822
TI  - Perioperative management of lung volume reduction patients.
AB  - Over the last 2 to 3 years, surgical lung volume reduction via sternotomy or
      thoracoscopy has been widely explored as an alternative to improve dyspnea,
      exercise tolerance, and lung mechanics in patients with severe emphysema. In this
      article, the authors describe the intra- and postoperative management of patients
      with severe airflow obstruction who undergo this procedure. Anesthesia
      techniques, extubation, ventilatory management, and overall medical and surgical
      care are reviewed. The most common postoperative complications also are reviewed,
      and management of these complications is discussed.

PMID- 9187823
TI  - Acute pulmonary allograft rejection. Mechanisms, diagnosis, and management.
AB  - Rejection is a common complication following lung transplantation, and can lead
      to considerable short- and long-term morbidity. As numbers and survival rates of
      lung transplant recipients increase, it is apparent that acute rejection can
      occur months or years after transplantation, and may be resistant to standard
      therapies. Mechanisms of acute rejection have been well studied in other solid
      organ transplant recipients, and are beginning to be addressed in the lung
      recipient. This article addresses some of the common issues of diagnosis and
      management of acute rejection which arise frequently during the care of lung
      transplant recipients.

PMID- 9187824
TI  - Prophylaxis post-transplant. The role of monitoring surveillance bronchoscopy and
      antimicrobials.
AB  - One of the key areas of successful organ transplantation is the prompt
      recognition and treatment of problems that otherwise can progress rapidly,
      leading to morbidity and mortality. Surveillance and prophylaxis are essential in
      the field of transplant medicine.

PMID- 9187825
TI  - Obliterative bronchiolitis.
AB  - Obliterative bronchiolitis following lung transplantation is common and
      potentially devastating. Its exact cause is undefined, but multiple immune and
      nonimmune processes contribute to its pathogenesis. Severe acute rejection and
      recurrent acute rejection have been shown to confer the greatest risk for
      obliterative bronchiolitis, signifying the central importance of alloimmunity in
      the disease process. Treatment of established disease with intensification of
      immune suppression has been of limited benefit, so current clinical strategies
      include early detection and minimization of risk. As our understanding of the
      disease evolves, it is hoped that effective interventions targeted at specific
      pathogenetic steps will emerge. In the meantime, obliterative bronchiolitis
      remains the most important and sinister long-term complication of lung
      transplantation.

PMID- 9187826
TI  - Infections in lung transplant recipients.
AB  - Advances in surgical technique and better knowledge of the physiologic and
      immunologic changes in the transplant population, combined with improved
      diagnostic tools and treatment strategies, have decreased the likelihood of early
      and, possibly, late mortality caused by a primary infection. Nevertheless,
      infection continues to be an important cause of death in both the early and late
      post-transplant periods. Risk of death attributable to infection after prolonged
      survival, however, is greatest in the setting of chronic rejection. The most
      significant advances in antimicrobial management have been in the area of
      prophylaxis. The effectiveness of prophylaxis against P carinii has virtually
      eliminated that organism as a cause of significant morbidity. Ganciclovir
      prophylaxis protocols require refinement but have been proved effective against
      CMV, although that virus continues to be a major pathogen in lung transplant
      recipients. Ultimately, a careful monitoring protocol and a high index of
      suspicion for infection requiring investigation and treatment are necessary in
      the ongoing care of lung transplant recipients. The approach to infections should
      be guided by the knowledge of the various factors that increase susceptibility to
      microorganisms and any previous culture and sensitivity results. As transplant
      physicians try to increase the donor pool through the use of donors who
      previously might have been rejected and through the potential of xeno
      transplantation, vigilance and research must be maintained.

PMID- 9187828
TI  - Nonpulmonary medical complications in the intermediate and long-term survivor.
AB  - This article deals with the nonpulmonary, non-infectious complications in
      intermediate and long-term survivors of lung transplantation. Although they are
      an infrequent cause of mortality, these disorders can cause significant morbidity
      in this population. Diseases associated with the gamut of medications used post
      transplant are specifically discussed, as are diseases caused by the direct
      immunosuppressive action of some of these drugs. General care of transplant
      patients also entails attention to their underlying diseases, and to routine
      medical considerations common to all patients.

PMID- 9187827
TI  - Review of immunosuppression for lung transplantation. Novel drugs, new uses for
      conventional immunosuppressants, and alternative strategies.
AB  - The history, pharmacokinetics, mechanisms of action, and experimental as well as
      clinical data on the immunosuppressive potential of the novel drugs tacrolimus
      (FK506), sirolimus (rapamycin), mycophenolic acid (mycophenolate mofetil), and
      leflunomide (and its malononitriloamide analogues) are provided. Novel approaches
      with the following conventional immunosuppressants are outlined: methotrexate,
      aerosolized immunosuppression and the implementation of steroid taper. Total
      lymphoid irradiation and photopheresis for treatment of recurrent rejection are
      also discussed.

PMID- 9187829
TI  - Psychosocial and ethical issues in surgical approaches to end-stage lung disease.
AB  - Heart-lung transplantation became a treatment option for end-stage lung
      parenchymal and vascular disease in 1981. Although many advances have occurred in
      the field surrounding donor selection, allograft preservation, surgical
      techniques, immunosuppression, and rejection and infection treatments, a shortage
      of cadaveric donors continues. This results in increased waiting times for the
      candidates, which in itself introduces an array of physical and psychological
      issues that must be addressed before transplant. This article examines the
      psychological factors evident in this period. In addition, ethical issues related
      to the allocation system and their impact on organ availability and, therefore,
      the time spent waiting for a lung transplant are presented.

PMID- 9187830
TI  - The cost of lung transplantation and the quality of life post-transplant.
AB  - As recently as the 1992 Report of the American Thoracic Society Workshop on Lung
      Transplantation, no QOL facts were given and no knowledge gaps related to QOL
      outcomes were cited. Even at the present time, the information in that area is
      based on a relatively small set of preliminary reports. Current information
      indicates that successful lung transplantation largely reverses the energy and
      physical mobility deficits reported by transplant candidates and that those
      improvements are sustained for at least several years after transplant.
      Recipients report improved health perceptions, fewer problems, and greater life
      satisfaction than candidates. The type and amount of QOL benefit appear to differ
      by underlying lung disorder, and recipients who develop obliterative
      bronchiolitis syndrome experience declines in QOL. Lung transplantation surgery
      is an expensive procedure initially, and costs remain high during follow-up.
      Little information is available on long-term QOL outcomes or cost-effectiveness.
      There is a compelling rationale for QOL research in lung transplantation. At the
      present time, some of the most challenging problems in transplantation, such as
      the selection of optimal timing for transplant and choice of immunosuppression
      medications, do not appear to have clear-cut survival or clinical benefits.
      Determination of the best approach to such problems is likely to hinge on
      patients' perceptions of the risk-to-benefit ratio, measured by their perceived
      QOL. Findings from QOL research need to be developed into interventions to
      enhance patient outcomes. As noted by Whitehead, QOL and potentially lethal
      noncompliance may be linked. Can we develop immune suppressive protocols that
      maintain clinical benefits while minimizing QOL burdens? Pilot studies suggest
      that QOL can be enhanced prior to transplant, and that health-related QOL prior
      to transplant may predict survival and clinical outcomes. As noted by Ramsey et
      al, multicenter studies are needed to achieve sufficient numbers for multivariate
      and subset analyses and to address issues such as the impact of diagnosis
      (indication for transplant) on QOL outcomes and cost-effectiveness. QOL and cost
      measures must be incorporated into large, longitudinal, multicenter clinical
      trials and observational studies to address those issues.

PMID- 9187831
TI  - Pediatric lung transplantation.
AB  - Pediatric lung transplantation is becoming more common, and with increasing
      experience there is increasing success. The most common indications for
      considering lung transplantation are cystic fibrosis, pulmonary vascular disease
      (usually due to congenital heart disease), and fibrotic lung disease. The
      contraindications and complications are similar to adult transplant patients,
      although post-transplant lymphoproliferative disease and airway complications may
      occur more frequently. The patients with cystic fibrosis face additional
      obstacles to the success of transplantation: airway colonization with Gram
      negative organisms, pancreatic insufficiency, glucose intolerance, and
      osteoporosis. The survival for children is comparable to adults, reaching about
      65% at 1 year, and 69% at 2 years.

PMID- 9187832
TI  - Naevogenesis: a hypothesis concerning the control of proliferation of melanocytes
      with special reference to the growth of intradermal naevi.
AB  - The pigmentary function of epidermal melanocytes depends on the donation of
      melanin granules to the surrounding surface structures. This involves transfer of
      cytoplasm (cytocrine transfer) from melanocytes to keratocytes, a process which
      requires competence of the donor cells and the availability of adjacent competent
      recipient cells. Donor cell competence involves the extension of dendrites and
      recipient cell competence consists of the ability of these cells to phagocytose
      peripheral portions of the melanocyte cytoplasm. Since there is a highly
      regulated mechanism for the control of cellular size which operates by inhibiting
      proliferation of cells that are below a critical volume, it is proposed that the
      continual removal of portions of the melanocyte cytoplasm by cytocrine transfer
      is responsible for inhibiting growth of the epidermal melanocyte population,
      accounting for their relatively low population density. It is proposed that
      inhibition of cytocrine transfer permits the proliferation of melanocytes.
      Cytocrine transfer may be inhibited by loss of competence of donor or recipient
      cells or by their relative displacement. Displacement of melanocytes into the
      dermis, out of range of potential recipient keratocytes, would, according to this
      hypothesis, result in melanocyte proliferation leading to the generation of
      localized aggregations of melanocytes (melanocytomas). It is proposed that this
      is the origin of acquired benign pigmented moles.

PMID- 9187833
TI  - Antiviral therapy for recurrent herpes simplex reconsidered.
AB  - The purpose of this paper is to present our long-time concern about the safety of
      using antiherpetic drugs over extended periods of time as a preventive therapy
      for recurrent herpetic attacks. It has been shown that when herpes simplex virus
      (HSV) is inactivated and has thus lost its cytolytic activity by exposure to
      certain chemicals or ultraviolet irradiation, it can cause neoplastic changes in
      mammalian cells. Therefore, substances that inhibit (but not absolutely
      eliminate) HSV replication for prolonged periods of time might be of potential
      danger for the development of cancer. It becomes incumbent upon us to ask
      ourselves whether the prolonged inhibitory effect of prophylactic antiviral drugs
      might not carry with it the same risks as has been proposed for other substances
      known to inhibit viral replication.

PMID- 9187835
TI  - Superficial spreading melanoma and blue naevus within naevus spilus-
      ultrastructural assessment of giant pigment granules.
AB  - BACKGROUND: Abnormal melanosomes occur in naevus spilus (NS). OBJECTIVE: To
      determine whether melanoma arising in NS contains abnormal melanosomes. METHODS:
      Light and electron microscopy of melanoma within NS and congenital naevus (Case
      1), and of blue naevus within NS (Case 2). Light microscopy of additional naevi
      and melanomas. RESULTS: The melanoma and NS (Case 1) both had large numbers of
      giant pigment granules (GPGs), demonstrated ultrastructurally to be melanosome
      macrocomplexes. These were not observed in a congenital naevus (Case 1), or in
      the blue naevus within NS (Case 2). Small numbers of GPGs were observed in 0/2
      NS, 8/16 benign naevi and 11/16 malignant melanomas (MMs). CONCLUSION: NS may be
      associated with other melanocytic tumours including MM and blue naevi; abnormal
      melanosomes in NS may also be present in the associated tumour. The prognostic
      importance of these is unknown, but occasional GPGs in melanocytic lesions are a
      frequent finding.

PMID- 9187834
TI  - Serum S100--a marker for disease monitoring in metastatic melanoma.
AB  - BACKGROUND: S100 proteins are low-molecular-weight calcium-binding proteins and
      appear to play an important role in various cellular processes such as cell
      division and differentiation. In histopathology, S100 is widely accepted as the
      marker of choice for immunohistochemical identification of malignant melanoma.
      When S100 was detected in the serum of patients with malignant melanoma, it was
      suggested that serum S100 may be a useful marker for the stage of disease.
      OBJECTIVE: The aim of this study was to examine serum S100 concentrations of
      patients with different stages of malignant melanoma and to determine the value
      of serum S100 in the follow-up of melanoma patients during treatment. METHODS:
      Sera were obtained from 73 melanoma patients in different stages of the disease.
      The control group consisted of 130 healthy subjects. In 4 patients with
      metastatic melanoma, serum S100 was measured serially. Serum levels were measured
      by a commercially available immunoradiometric assay. RESULTS: While only 1 out of
      25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage
      III, 21.4%) showed detectable serum S100 levels, 27 of 34 patients with
      disseminated disease (stage IV, 79.4%) had elevated serum S100. Interestingly,
      rising levels of serum S100 in the serial measurement indicated progression of
      the disease, and a complete decline reflected 2 patient remissions. CONCLUSION:
      The data support the value of serum S100 as a clinical marker for progression of
      metastatic melanoma and serological monitoring during systemic therapies.

PMID- 9187836
TI  - ARA and EADV criteria for classification of systemic lupus erythematosus in
      patients with cutaneous lupus erythematosus.
AB  - OBJECTIVE: To verify (1) how many patients with cutaneous lupus erythematosus
      (CLE) fulfill 4 or more American Rheumatism Association (ARA) and European
      Academy of Dermatology and Venereology (EADV) criteria for classification of
      systemic lupus erythematosus (SLE); (2) which criteria are mostly fulfilled; (3)
      the severity of the disease in patients fulfilling criteria; (4) how many
      patients with systemic involvement fail to fulfill 4 ARA and EADV criteria.
      METHODS: We studied 207 patients with chronic and subacute CLE, classified
      according to ARA and EADV criteria. RESULTS: Twenty-four patients with localized
      discoid (L-DLE; 21.8%), 22 with disseminated discoid (D-DLE; 30.5%) and 7 with
      subacute CLE (SCLE; 28%) had 4 or more ARA criteria. With EADV criteria, these
      figures fell to 7 (6.4%), 7 (9.7%) and 6 (24%), respectively. Only 3 L-DLE
      (2.7%), 5 D-DLE (6.9%) and 3 SCLE cases (12%) defined as SLE by ARA criteria and
      1, 3 and 3, respectively, by EADV criteria had a renal or neurological disorder,
      hemolytic anemia and/or thrombocytopenia, vasculitis or serositis. ARA criteria
      did not classify 7 patients with a similar visceral involvement, while EADV
      criteria failed in 11 patients. CONCLUSION: In our patients, ARA criteria showed
      a sensitivity of 88%, a specificity of 79%, a positive predictive value of 56%
      and a negative predictive value of 96%. EADV criteria showed a sensitivity of
      only 64%, but a specificity of 93%, a positive predictive value of 61% and a
      negative predictive value of 94%. ARA criteria should not be used in CLE patients
      as they are too sensitive, poorly specific and altogether misleading. EADV
      criteria are more specific, but less sensitive.

PMID- 9187837
TI  - Human skin lymph derived from irritant and allergic contact dermatitis:
      interleukin 10 is increased selectively in elicitation reactions.
AB  - BACKGROUND: Recent reports suggested an immunomodulatory role for interleukin 10
      (IL-10) in contact hypersensitivity. OBJECTIVE: To investigate if IL-10 is
      important in the regulation of irritant and allergic contact dermatitis (CD), IL
      10 and interferon gamma (IFN-gamma) protein levels were measured in normal skin
      lymph, in lymph derived from irritant and allergic (primary sensitization and
      elicitation) CD and in skin blister fluid from an elicitation reaction. METHODS:
      A superficial lymph vessel was cannulated microsurgically on the lower leg of 18
      healthy volunteers. Lymph was collected twice daily. Protein levels of IL-10 and
      IFN-gamma were determined using commercially available ELISA kits and messenger
      RNA was estimated by a reverse-transcriptase polymerase chain reaction (PCR)
      method. RESULTS: Whereas the IL-10 levels in lymph derived from irritant CD and
      primary sensitization of allergic CD, similarly to those obtained from normal
      untreated skin, remained below 4.4 pg/ml, the IL-10 levels increased manifold
      both in the primary allergic reaction (928.5 pg/ml) and the elicitation of
      allergic CD (124 pg/ml). The levels of IFN-gamma also increased in all volunteers
      exhibiting an eczematous skin reaction and showed a tendency to be inversely
      correlated with IL-10. Using a reverse-transcriptase PCR, the expression of IL-10
      and IFN-gamma in cells from lymph and from blister fluid was examined. While
      signals for IFN-gamma were not found, specific transcripts for IL-10 were
      detected in all samples examined, indicating that cells circulating in the lymph
      may also contribute to the IL-10 production measured. The IL-10 mRNA signal,
      however, was markedly stronger in lymph and epidermal blister cells from the
      elicitation reactions as compared to the signal in lymph cells derived from
      normal skin and from the primary sensitization of allergic CD. CONCLUSION: IL-10
      may limit and down-regulate elicitation reactions by inhibiting cytokine and
      antigen-presenting cell functions in the skin and in the skin-associated lymphoid
      tissue.

PMID- 9187838
TI  - Kaposi's sarcoma in renal-transplant recipients: experience at the Catholic
      University in Rome, 1988-1996.
AB  - BACKGROUND: The incidence of Kaposi's sarcoma (KS) in patients transplanted at
      the Organ Transplant Center of Catholic University in Rome appears to have
      increased in recent years. OBJECTIVE: To describe the clinical characteristics of
      KS in a group of transplant recipients. METHODS: Over 8 years, a total of 302
      renal-transplant recipients were followed. When KS was suspected, histology and
      staging procedures were performed. RESULTS: Ten cases of KS have been diagnosed
      (8 males, 2 females; age 46.4 +/- 9.4 years); 4 of them were on triple therapy.
      All the patients were HIV-1 seronegative. The onset of KS occurred 3 months to 4
      years after transplantation (21.1 +/- 17.6 months). The disease was limited to
      the skin in 6 cases and involved internal organs in the remaining 4. Four
      patients experienced complete remission of the disease following reduction of the
      immunosuppressive therapy. CONCLUSION: The high incidence of KS in this
      population (2.98%), as compared to that reported in other transplant patient
      groups, suggests that, besides viral infection, genetic predisposition may play a
      pathogenetic role. However, immunosuppression is the leading factor in transplant
      patients.

PMID- 9187839
TI  - Increased risk for opportunistic infections during chemotherapy in HIV-infected
      patients with Kaposi's sarcoma.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is the most frequent neoplasm in patients with
      AIDS, responsible for death in about 20-30% of the affected patients. OBJECTIVE:
      To determine the frequency of opportunistic infections (OI) and change of CD4+
      cell counts in patients with KS treated with chemotherapy compared to a group of
      matched-pair patients without chemotherapy. METHODS: In a prospective study, the
      clinical courses of 35 HIV-infected patients with KS treated with chemotherapy
      were compared with 35 matched-pair patients without chemotherapy. RESULTS: During
      the observation period of 6 months, 11 OI occurred in 10 patients of the
      chemotherapy group and 5 OI in 5 patients of the control group. With respect to
      the changes of CD4+ cell counts, no significant differences could be observed.
      CONCLUSION: The risk for OI in HIV-infected patients with KS is increased while
      receiving chemotherapy. This should be reflected upon when chemotherapy is taken
      into consideration.

PMID- 9187840
TI  - Electron resonance studies on the influence of anionic surfactants on human skin.
AB  - BACKGROUND: When skin is exposed to chemicals, raw materials interact with the
      lipid structure of the stratum corneum. At least two types of disorders can be
      distinguished--that of alkyl chains inside one lipid bilayer and that of lipid
      layer arrangement. Electron spin resonance (ESR) spectroscopy of a nitroxide spin
      label is a valuable method in the study of biological membranes. OBJECTIVE: These
      experiments define the effect of anionic surfactants on the lipid bilayer of
      human stratum corneum. METHODS: 5-Doxyl stearic acid (5-DSA) was used as the spin
      label. Sodium lauryl sulfate (SLS) and sodium lauroyl-L-glutamate (SLG) were the
      anionic surfactants studied. ESR spectrum measurements of surfactant-treated
      stratum corneum were performed and order parameters calculated. RESULTS: 1% of
      SLS leads to an obvious change in ESR spectra--from strongly to weakly
      immobilized spectra. The molecular motion of spin labels (5-DSA) in SLS-treated
      stratum corneum is different from that of spin labels in the untreated stratum
      corneum. The ESR spectra suggest that SLS affects the spin label binding to the
      lipid membrane and causes an increase in the mobility of bilayers. On the other
      hand, there were minimal changes in ESR spectra of 1% of SLG-treated stratum
      corneum. An increase in fluidity of skin lipid bilayers suggests a decrease in
      the skin barrier function. CONCLUSION: ESR may provide a facile and robust method
      to define the subclinical irritancy potential of anionic surfactants and other
      materials.

PMID- 9187841
TI  - Occupational dermatoses in cheese makers: frequent association of irritant,
      allergic and protein contact dermatitis.
AB  - BACKGROUND: Few data are available on occupational dermatoses in cheese makers.
      OBJECTIVE: The purpose of the present study was to investigate occupationally
      related skin diseases in cheese makers. METHOD: In a retrospective study we
      analyzed 400 patients with occupational dermatoses which presented for expert
      opinion evaluation at our institution (1990-1995). RESULTS: Four patients with
      hand eczema acquired in cheese dairies were identified. All patients had a
      decreased alkali resistance. Atopy was a further risk factor in 2 patients. Three
      out of 4 patients were patch test positive for occupationally related substances
      and demonstrated also immediate skin test reactions to various milk products.
      Therefore, these patients had concurrent allergic contact and protein contact
      dermatitis. CONCLUSION: The diagnosis of concurrent allergic and protein contact
      dermatitis has to be considered in occupational dermatoses related to cheese
      making.

PMID- 9187842
TI  - Petrolatum prevents irritation in a human cumulative exposure model in vivo.
AB  - BACKGROUND: Protective creams (PCs) have been studied in different models
      indicating a protective effect of some products. In order to compare PCs in
      different studies, a generic reference standard should be available. OBJECTIVE:
      The purpose of this study was to investigate if petrolatum prevents epidermal
      barrier disruption induced by various irritants in a repetitive irritation test
      (RIT) and to assess its potential as a standard reference product. METHODS: White
      petrolatum was evaluated against a set of 4 irritants [10% sodium lauryl sulphate
      (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene
      (TOL)] in the RIT. Twenty subjects were tested on the paravertebral skin of the
      midback. Irritation was assessed by visual scoring, transepidermal water loss and
      colorimetry. RESULTS: Petrolatum was very effective against SLS, NaOH and LA
      irritation, and it provided a moderate protection against TOL. CONCLUSION:
      Petrolatum can be recommended as a standard reference substance against which PCs
      may be compared as it is effective against water-soluble and water-insoluble
      irritants in a standardized test procedure.

PMID- 9187843
TI  - Low-dose danazol in the treatment of livedoid vasculitis.
AB  - BACKGROUND: Livedoid vasculitis is characterized clinically by smooth or
      depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia
      with or without preceding purpuric infiltrated papules and plaques and
      histologically by intravascular deposition of fibrin. Its etiology remains
      obscure and therapy very difficult. OBJECTIVE: Our purpose was to test the
      efficacy of low-dose danazol in the treatment of livedoid vasculitis. METHODS:
      Seven patients with active lesions of livedoid vasculitis were treated with low
      dose danazol (200 mg, orally, daily). Laboratory coagulation and fibrinolysis
      parameters, including antithrombin III, protein C, protein S, tissue plasminogen
      activator, plasminogen, alpha 2-antiplasmin and fibrinogen, were evaluated before
      and during the therapy. RESULTS: Six of the 7 patients completed the treatment.
      After the therapy, all 6 patients had rapid cessation of new lesion formation,
      prompt reduction in their pain and healing of ulcers. A significant elevation of
      plasminogen and a decrease in fibrinogen levels were noted 1 month after
      initiation of the therapy (p = 0.028). The level of fibrinogen seemed to parallel
      the disease activity in individual patients. In addition, in most of these
      patients, the levels of antithrombin III, protein C, protein S and alpha 2
      antiplasmin tended to increase after the treatment. However, the differences were
      not statistically significant. Abnormalities of tissue plasminogen activator
      levels were less consistent. Low-dose danazol was well tolerated without major
      side effects. CONCLUSION: We concluded that low-dose danazol was effective in the
      treatment of livedoid vasculitis, without unacceptable side effects.

PMID- 9187844
TI  - Phototherapy of acne vulgaris with visible light.
AB  - BACKGROUND: Sun exposure has a beneficial effect on acne vulgaris, but it is not
      clear which wavelengths contribute to the favourable effect. OBJECTIVE: The aim
      of the study was to investigate the effect of visible light on acne vulgaris and
      define the most effective wavelengths. METHODS: Thirty patients (15 men and 15
      women) with mild to moderate acne vulgaris, involving the face and/or the back
      and/or the chest, were treated with three different light sources. They were
      treated 3 times a week, for a total of 7 weeks, each field for 20 min per
      session. RESULTS: All the light sources using 'full spectrum', green and violet
      improved the acne, leading to 14% (p > 0.10), 22% (p < 0.05) and 30% (p < 0.02)
      improvement, respectively. No statistically significant differences between the
      three different light sources were found, although there was a tendency that
      violet light was better than the other light qualities. No side-effects were
      observed. CONCLUSION: Visible light is a moderately effective alternative for
      treatment of acne vulgaris.

PMID- 9187845
TI  - Dermabrasion of congenital nevocellular nevi: experience in 215 patients.
AB  - BACKGROUND: The indication for surgical treatment of congenital nevocellular nevi
      results from aesthetic-cosmetic consideration as well as from the increased risk
      of melanomatous transformation. OBJECTIVE: We evaluated the outcome after
      dermabrasion of congenital nevi of different sizes and treated at different ages.
      METHODS: 215 patients treated by dermabrasion during the years 1979-1995 were
      examined at a median interval of 24 months postoperatively. RESULTS: No
      postoperative development of malignant melanoma arising from the congenital nevus
      was seen in any of the patients during the time of follow-up. No serious long
      term complications were seen. Hypertrophic scars were seen within parts of the
      operation field in 14.6%, but in those the cosmetic result was still
      satisfactory. Permanent reduction of pigmentation to 0-20% as compared with the
      preoperative status was achieved if treatment was performed within the newborn
      period. In case of large and giant nevi, permanent removal of pigmentation was
      better than in small or medium-sized nevi. CONCLUSION: Dermabrasion proved to be
      an adequate modality for removal of pigmentation in the therapy of large and
      giant congenital nevocellular nevi when assessed within 2 years following the
      procedure. Early treatment is crucial for permanent removal of pigmentation. Long
      term effects remain to be adequately monitored.

PMID- 9187847
TI  - Cutaneous granulomas as a presenting sign in ataxia-telangiectasia.
AB  - Telangiectasia is the classic cutaneous finding of ataxia-telangiectasia (AT) and
      is often the physical finding that suggests the diagnosis. We report a patient in
      whom noninfectious cutaneous granulomas were the presenting cutaneous feature of
      AT and discuss immunodeficiency syndromes that are associated with similar
      cutaneous granulomas.

PMID- 9187846
TI  - Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone
      and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma.
AB  - BACKGROUND: Response of cutaneous T-cell lymphoma (CTCL) to systemic chemotherapy
      is unsatisfactory: despite an initially high response rate (RR), duration is
      always short-lived. OBJECTIVE: To investigate the capability of a third
      generation regimen including idarubicin in improving RR and response duration in
      CTCL patients. METHODS: Twenty-five patients with advanced CTCL (stages IIB and
      IV) were treated with a 12-week polychemotherapeutic regimen (VICOP-B), which
      foresees the use of idarubicin in association with etoposide, cyclophosphamide,
      vincristine, prednisone and bleomycin. RESULTS: The overall objective RR was 80%
      (36% complete response). The mycosis fungoides (MF) RR was 84%, with a median
      duration of 8.7 months. The pleomorphic-lymphoma RR was higher (100%), but the
      corresponding response duration was shorter (median: 3 months). No responses were
      documented in Sezary syndrome. CONCLUSION: VICOP-B regimen is effective and
      feasible as first-line chemotherapy in advanced MF, with or without
      extracutaneous involvement.

PMID- 9187848
TI  - Congenitally acquired herpes zoster infection in a newborn.
AB  - We report a case of congenitally acquired herpes zoster infection in a newborn
      whose mother suffered from varicella in her eighth month of pregnancy. The
      newborn had vesicles with limited distribution on the left C7 region. Herpes
      zoster infection was clinically suspected and confirmed by the Tzanck test and a
      high titer of anti-varicella-zoster-virus immunoglobulin M (x1,280).

PMID- 9187849
TI  - A new case of extensive congenital erosions and vesicles healing with reticulate
      scarring.
AB  - Congenital erosions and vesicles that heal with reticulate scarring comprise a
      new entity first described in 1985 in 3 girls aged 3, 5 and 6 years. Two years
      later, an 8-year-old boy in whom the skin lesions were accompanied by
      neurological disorders was described, as in one of the patients described in the
      1985 study. In 1990, similar findings were reported in a neonate, and recently
      the 7th case has been reported in the American literature. We describe an 8-month
      old infant born with cutaneous lesions that subsequently formed reticulate scars
      peculiar to this clinical entity, which is characterized by variable clinical and
      histological expression.

PMID- 9187850
TI  - Vinorelbine therapy for Kaposi's sarcoma in a kidney transplant patient.
AB  - We report the case of a patient with Kaposi's sarcoma after kidney
      transplantation. Despite the discontinuation of azathioprine and a reduction in
      the cyclosporin dosage, the disease continued to evolve, and antineoplastic
      treatment became necessary. After 14 cycles of vinorelbine chemotherapy, there
      was a 75% regression of the initial lesions, despite the continuation of
      cyclosporin A.

PMID- 9187851
TI  - Linear IgA bullous dermatosis after contact with sodium hypochlorite.
AB  - The onset of linear IgA bullous dermatosis (LABD) is generally spontaneous, but a
      number of cases of LABD have been reported either following drug exposure or in
      association with malignancies. We describe a patient who developed a vesicular
      eruption shortly after an irritant dermatitis caused by the contact with a
      detergent containing sodium hypochlorite. Direct immunofluorescence revealed
      linear deposits of IgA and C3 in the epidermal basement membrane. The patient's
      serum contained IgA that immunoblotted a 180-kD polypeptide in extracts of human
      keratinocytes. The patient responded promptly to therapy with dapsone. We suggest
      a possible pathogenetic relationship between the chemical dermatitis and LABD in
      this patient.

PMID- 9187852
TI  - Anaplastic progression of classic Kaposi's sarcoma.
AB  - We describe a case of classic Kaposi's sarcoma (KS) in an Italian HIV-negative
      patient, with bone involvement and progression to anaplastic histotype. At the
      age of 22, violaceous patches of KS appeared on his feet. At the age of 50, he
      noted the appearance of a violaceous firm nodule on his right wrist. The lesions
      grew rapidly and became ulcerated. Radiotherapy led to a complete remission of
      symptoms. At the age of 55, a subcutaneous nodule developed on the proximal third
      of the right forearm associated with a wide painful edema of the right forearm
      and the proximal third of the right arm. The nodule enlarged rapidly, and an X
      ray of the right forearm revealed the presence of a large osteolytic area of the
      ulna. A biopsy specimen from the right ulna showed bone erosion by a mesenchymal
      neoplasia with a high degree of malignancy. The right arm was amputated, and
      histologic examination of the surgical material confirmed the diagnosis of
      undifferentiated spindle-cell malignant neoplasia strongly positive for factor
      VII-related antigen and CD34 antigen. Three years after surgical treatment, no
      recurrences have been observed.

PMID- 9187853
TI  - Keratoacanthoma developing in prurigo nodularis treated with cryotherapy.
AB  - We describe an elderly woman in whom keratoacanthoma developed from one nodule of
      prurigo nodularis that had been treated with cryotherapy for 3 months. Since in
      our case keratoacanthoma developed after treatment with liquid nitrogen for
      prurigo nodularis which had been constantly scratched in the past, we hypothesize
      that irritations of cryotherapy in addition to repeated mechanical traumas of
      scratching might have played a role in the formation of this tumor.

PMID- 9187854
TI  - Immunohistochemistry with monoclonal antibody against Candida albicans mannan
      antigen demonstrates cutaneous Candida granulomas as evidence of Candida sepsis
      in an immunosuppressed host.
AB  - We report the occurrence of invasive Candida albicans infection with disseminated
      cutaneous Candida granulomas in a patient with aplastic anaemia after viral
      hepatitis. Fungal elements in a skin biopsy specimen were detected by PAS stain
      and identified as Candida sp. by immunohistochemistry directed against the C.
      albicans mannan surface antigen. Based on rapid diagnosis of Candida granuloma
      and by Candida-positive cultures of blood and swabs, systemic treatment with
      liposomal amphotericin B led to survival of the patient.

PMID- 9187856
TI  - Leiomyoma of the scrotum.
AB  - Leiomyoma is a benign tumor derived from smooth muscle. Leiomyoma of the scrotum
      arising from the tunica dartos is exceedingly rare. We describe the case of a 51
      year-old Japanese man with this disease entity.

PMID- 9187855
TI  - Recurrent ulcerations on both legs since early childhood due to a factor V gene
      mutation.
AB  - We describe the case of a young man who suffered from recurrent ulcerations on
      both legs since his early childhood as a result of two coagulation factor
      abnormalities: factor V gene mutation causing microthrombotic occlusions and
      subsequently ulcerations and an intermittent factor XIII deficiency responsible
      for retarded wound healing.

PMID- 9187857
TI  - Primary digital clubbing associated with palmoplantar keratoderma.
AB  - The association of hereditary palmoplantar keratoderma and idiopathic clubbing of
      the digits in the same patient is uncommon. The differential diagnosis includes
      the Bureau-Barriere-Thomas syndrome, primary pachydermoperiostosis, Fischer's and
      Volavsek's syndromes, and palmoplantar keratoderma Vorner. A 30-year-old woman
      with palmoplantar keratoderma and clubbing of the fingers since the age of 13
      years is presented.

PMID- 9187858
TI  - Interferon alpha gel for herpes zoster.

PMID- 9187859
TI  - Rapid improvement of subacute cutaneous lupus erythematosus with low-dose
      methotrexate.

PMID- 9187860
TI  - Intraepidermal IgA pustulosis associated with monoclonal IgA gammopathy in an HIV
      infected patient.

PMID- 9187861
TI  - Remission of lichen amyloidosus after treatment with acitretin.

PMID- 9187862
TI  - Occupational high-pressure injection injury of the hand.

PMID- 9187863
TI  - Retinoids in lichen planus.

PMID- 9187864
TI  - Muscle activation and force production during bilateral and unilateral concentric
      and isometric contractions of the knee extensors in men and women at different
      ages.
AB  - In experiment I ten young men (29 +/- 3 yrs; M30), 12 middle-aged men (50 +/- 4
      yrs; M50) and 12 women (48 +/- 5 yrs; W50), 12 elderly men (67 +/- 4 yrs; M70)
      and 12 women (68 +/- 4 yrs; W70) volunteered for subjects for examination of
      maximal 1 RM strength and electromyographic activity of the knee extensor muscles
      during the bilateral and unilateral concentric contraction on a variable
      resistance knee extension dynamometer. In experiment II 10 young (Y) men (29 +/-
      5 yrs) and 10 older (O) men (61 +/- 4 yrs) were examined for their maximal
      voluntary isometric force and force-time curves and electromyographic activity of
      the knee extensor muscles during the bilateral and unilateral contractions. The
      bilateral 1 RM of 165.5 +/- 25.5 kg in M30 was greater (p < 0.01) than that of
      127.7 +/- 24.5 kg recorded for M50 the latter being also greater (p < 0.05) than
      that of 109.0 +/- 17.7 kg recorded for M70. The bilateral value of 87.4 +/- 13.4
      kg in W50 was greater (p < 0.05) than that of 69.9 +/- 15.0 kg recorded for W70.
      The bilateral 1 RM values were slightly greater than the summed unilateral 1 RM
      values in all groups M50, W50 and W70 showing a significant (p < 0.05)
      difference. All groups showed slightly (ns.) greater mean maximal integrated EMG
      values during the bilateral conditions in comparison to that of the corresponding
      unilateral condition. The maximal isometric forces in Y men were 25% greater (p <
      0.001) than in O men. In both groups the bilateral forces were somewhat greater
      (p < 0.05) than the summed unilateral forces and the bilateral IEMG values
      slightly (ns.) greater than the corresponding unilateral IEMG values. The early
      forces on the force-time curve were much greater (p < 0.05-0.001) in Y than O men
      in both conditions. The present findings suggest that both maximal voluntary
      isometric and concentric force, and especially explosive strength of the knee
      extensors decrease greatly with increasing age probably due to selective muscle
      atrophy and/or possible decreases in the amount or rate of voluntary activation
      of the muscles. However, no bilateral deficit could be found indicating that the
      central nervous system in a simple single joint isometric and maximal 1 RM
      concentric force production of the knee extensors was capable of activation of
      the two bilateral muscle groups simultaneously independent of age and sex of the
      subject. To which extent the activation and force production of the muscles would
      be different in terms of the bilateral deficit during various multijoint
      exercises utilizing isometric and higher velocity concentric, eccentric and
      various stretch shortening cycle exercise needs to be examined in the future.

PMID- 9187865
TI  - Evaluation of diaphragm electromyogram contamination during progressive
      inspiratory maneuvers in humans.
AB  - The diaphragm electromyogram (EMGdi) is susceptible to contamination by non
      diaphragm related electrical signals such as the ECG, electrode motion artifacts,
      and other sources of noise. It is difficult to distinguish between these
      contaminating signals and those that are representative of the non-contaminated
      EMGdi, especially during periods when the EMGdi amplitude is relatively small, as
      during mild contractions of the diaphragm. The aim of the present study was to
      evaluate how contaminating signals influence the EMGdi power spectrum center
      frequency (CF) during progressive inspiratory maneuvers. EMGdi and
      transdiaphragmatic pressure (Pdi) were measured via an esophageal electrode in
      eight patients with cervical cord injury performing inspiratory capacity (IC)
      maneuvers. The influence of the contaminating sources on CF was evaluated by two
      spectral deformation indices, one which is sensitive to both high and low
      frequency spectral deformation (omega index), and the other which is sensitive to
      high frequency deformation only (CF1000/CF500 index). The results indicated that
      EMGdi CF values scattered over a wide frequency range, particularly when the
      signals were obtained at Pdi levels less than 15% of Pdimax, or at lung volumes
      less than 30% of IC. When the spectral deformation indices were applied, the
      scattering in CF values was drastically reduced. This was expressed by a factor
      of 4 reduction in the coefficient of variation of the CF values. The majority of
      the excluded EMGdi signals (i.e. not satisfying the spectral deformation index
      inclusion levels), had low CF values mainly due to the presence of electrode
      motion artifacts. It was concluded that: 1) The majority of EMGdi power spectrums
      are deformed early on during unloaded inspirations, and their CF values should be
      carefully interpreted as being representative of diaphragm function. 2) The
      relative contribution of contaminating signals in the EMGdi decreases
      proportionally throughout the first two thirds of an inspiration to IC. 3) The
      use of visual inspection of the signal in the time domain is questionable as a
      method to discriminate non-contaminated signals. 4) Analysis of the signal in the
      frequency domain makes it possible to detect the influence of signal
      contamination.

PMID- 9187866
TI  - Segmental conduction times in the motor nervous system.
AB  - The study was performed in 30 normal subjects (24 females and 6 males) with an
      age range between 18 and 55 years and a height range between 154 and 188 cm.
      Electrical stimulation was applied to the peroneal nerve with simultaneous
      recording of the orthodromic response (MEP-M) and F-wave (MEP-F) from the
      tibialis anterior (TA) and extensor digitorum brevis muscles (EDB). Magnetic
      stimulation of the L5 level and cerebral cortex was applied using different coils
      with simultaneous recording of responses from the right and left TA and EDB
      muscles. Mean normative values and formulae of linear regression were established
      within the observed correlations with height for the parameters measured
      (latencies) and derived parameters (segmental conduction times). A software
      system was developed which allows the readout of the selected parameter values
      from the Mystro device, calculation of the derived parameters, and classification
      of the results according to 95% confidence intervals for the parameters obtained
      in the group of normal subjects included in the study. This fast and painless
      investigation, which carries no risk to the patient, should prove useful in the
      electrophysiological diagnosis of motor pathway function including the entire
      length.

PMID- 9187867
TI  - Event-related potentials (ERPs) associated with omitted somatosensory stimuli.
AB  - Late positive ERP components elicited by omitted somatosensory stimuli in passive
      paradigm (passive MSPP) and in active time-estimation paradigm (active MSPP) were
      studied in healthy subjects with single-trial analysis and conventional averages.
      The active MSPP was also compared with P3 component elicited by somatosensory
      target stimuli (target P3). Single-trial analysis showed clearly discernible
      passive MSPP in response to omitted stimuli of the median nerve, whereas passive
      MSPP was hardly detected in response to omitted stimuli of the index finger. The
      subjects might pay passive attention to absence of somatosensory stimuli together
      with absence of the thumb muscle twitches. Single-trial analysis revealed a
      significantly greater latency fluctuation in passive MSPP than in active MSPP.
      The active MSPP showed a greater latency fluctuation than the target P3. The
      active MSPP showed a significantly longer latency and a smaller amplitude than
      the target P3 in conventional averages. Topography of active MSPP showed a
      symmetric central-parietal maximal distribution similar to that of target P3.

PMID- 9187868
TI  - Simulation of the influence of different factors on the motor nerve condition
      velocity measurement. Part 1: Normal conditions.
AB  - The result of a motor nerve conduction velocity measurement is dependent of a row
      of factors which will influence the measurement. These factors have been tested
      extensively in healthy volunteers. However, under pathological conditions it is
      not known to what degree the reported velocities are influenced by biological and
      technical factors. In an attempt to broaden our knowledge on the matter, a model
      was made to test different factors under varying conditions. Part I describes the
      model and reports results from calculations on simulated normal nerves. The
      results are in concert with results from healthy volunteers. Part II reports on
      results in pathological conducting nerves. The effect of the different factors
      affecting the nerve conduction velocities are shown. A simulation of doing a
      measurement twice and reporting the average showed a marked decrease of the
      variability in the reported nerve conduction velocity. This was more effective
      than eliminating any of the other factors influencing the measured conduction
      velocity.

PMID- 9187869
TI  - The origin of R2 of the blink reflex recorded on the affected side of patients
      with complete facial nerve paralysis.
AB  - The possible mechanisms contributing to the generation of R2-like response were
      investigated in 19 patients with complete facial nerve paralysis, where the
      efferent limb of the reflex arc is absent. The first possibility that potentials
      produced by the unaffected orbicularis oculi (0.0c) are conducted to the
      reference electrode taped over the nose was confirmed as the amplitude of R2 on
      the affected side was significantly reduced when the reference electrode was
      removed from the nose and taped on the ear lobule. The second possibility of
      volume conducted potentials produced by muscular generator in temporalis and
      masseter muscles through trigemino-trigeminal reflex was suggested in some
      patients based on three reproducible observations: (1) EMG activity of high
      amplitude could be recorded with electrodes taped over the affected 0.0c muscle
      during voluntary teeth clenching, (2) R2-like responses were recorded in patients
      with bilateral complete facial paralysis, (3) R2-like responses were recorded
      from temporalis and masseter muscles. The contribution of extraocular muscles
      could be discounted as R2 could be recorded from patients with Mobius's syndrome
      who had complete bilateral facio-ocular paralysis. The results of the present
      study further support the greater value of R1--rather than R2--in predicting
      clinical outcome of patients with peripheral facial nerve palsy.

PMID- 9187870
TI  - Occult obstetric trauma and anal incontinence.
AB  - Obstetric trauma is by far the commonest cause of anal incontinence in women.
      Denervation and reinnervation of the pelvic floor and anal sphincter following
      vaginal delivery has been previously demonstrated. The advent of anal
      endosonography, however, has enabled the identification of occult anal sphincter
      defects following vaginal delivery. It is now possible to identify risk factors
      and change obstetric practice accordingly so as to minimize anorectal morbidity.

PMID- 9187871
TI  - Medical causes of faecal incontinence.
AB  - Faecal incontinence can result from a disturbance in any one of the multiple
      factors which maintain continence. In practice, faecal incontinence is most
      commonly seen in women who have had children. This symptom can also be seen in
      other patient groups, who may in addition have had children, and this article
      will discuss the mechanisms involved in the loss of continence in diabetics and
      patients with multiple sclerosis.

PMID- 9187872
TI  - Biofeedback in the treatment of faecal incontinence.
AB  - Faecal incontinence is a distressing condition that affects approximately 1% of
      the population. Poor anal canal function can be determined by physiological
      testing using manometry and electromyographic techniques. Surgical repair of the
      anal canal does not always restore continence but biofeedback training either
      alone or in combination with other techniques such as muscle stimulation allows
      restoration of some degree of functional integrity of the anal canal musculature.
      Biofeedback training offers a non-surgical approach to incontinence with good
      success rates and prolonged after benefits. However, patient motivation is
      crucial as the exercise techniques taught need to be continued on a permanent
      basis if continence is to be maintained.

PMID- 9187873
TI  - The electrically stimulated gracilis neo-anal sphincter.
AB  - Many patients with incontinence gain no relief from their symptoms following
      traditional surgical treatment and by necessity resort to a stoma. A number of
      attempts have been made to replace damaged or excised sphincters using the
      gracilis muscle to fashion a neo-anal sphincter. The results of the published
      series using the technique of unstimulated graciloplasty for the treatment of
      anal incontinence and in total anorectal reconstruction are reviewed. The results
      of these series are conflicting. In an effort to improve on these results the
      electrically stimulated neo-anal sphincter has been developed. The rationale
      behind its development and its evolution are discussed. The efficacy of the
      procedure in treating patients with incontinence or as part of total anorectal
      reconstruction is assessed.

PMID- 9187874
TI  - Pharmacology of the internal anal sphincter and abnormalities in faecal
      incontinence.
AB  - Studies of anorectal physiology and in-vivo experiments on the innervation of the
      anorectum have provided considerable information about anorectal function.
      Additional information regarding the receptors and nerves involved in the control
      of the internal anal sphincter function has been obtained from in-vitro studies
      of isolated muscle strips of the internal anal sphincter.

PMID- 9187875
TI  - Role of gastric mucosal cytokines in the immunopathogenesis of Helicobacter
      pylori infection: new hypotheses but still few certitudes.
AB  - Since the recognition of Helicobacter pylori as a pathogen involved in chronic
      gastritis, peptic ulcers and gastric cancer, many studies have shown that
      clinical manifestations of H. pylori infection occur only in a minority of
      infected patients. Studies of the genomic diversity of this bacterium show
      relations of some bacterial characteristics with pathology. Imbalanced host
      response to infection may also play a major role in the clinical expression of H.
      pylori infection. Gastric epithelial cells are involved in the process, as well
      as lymphocytes and other immune cells of the underlying gastric tissue. A better
      understanding of the immunopathogenesis of H. pylori infection is required to
      understand the exact role of both the strain and the host.

PMID- 9187876
TI  - Helicobacter pylori stimulates granulocyte-macrophage colony-stimulating factor
      (GM-CSF) production from cultured antral biopsies and a human gastric epithelial
      cell line.
AB  - OBJECTIVE: To examine the regulation of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) production by gastric epithelial cells in Helicobacter pylori
      infection. DESIGN: The effect of H. pylori infection on gastric GM-CSF production
      was assessed using short-term culture of antral biopsies. The mechanism of GM-CSF
      induction was investigated using a gastric epithelial cancer cell line. METHODS:
      Production of GM-CSF was assessed by enzyme-linked immunosorbent assay. The
      mechanism of stimulation of GM-CSF production was examined by co-culture of AGS
      carcinoma cells with H. pylori and specific stimulants and inhibitors. RESULTS:
      Biopsies from H. pylori-negative patients in the basal state did not produce GM
      CSF. However, over 24 h in the presence of the active phorbol ester, phorbol
      myristate acetate (PMA), significant release of GM-CSF was seen. H. pylori
      positive biopsies produced significantly more GM-CSF in both the unstimulated and
      PMA-stimulated state than H. pylori-negative biopsies. Constitutive release of GM
      CSF from cultured human gastric AGS cells could be significantly enhanced by co
      culture with live H. pylori or the addition of interleukin-1 beta, tumour
      necrosis factor alpha and PMA, but not by exposure to forskolin. The protein
      kinase C inhibitor staurosporine abolished the stimulatory effect of PMA on AGS
      cells, whereas the protein-tyrosine kinase inhibitor herbimycin A prevented the
      stimulation of GM-CSF production seen with H. pylori and both cytokines.
      CONCLUSION: H. pylori enhances GM-CSF production by gastric epithelia. H. pylori
      appears to stimulate gastric epithelial cells directly to produce GM-CSF and this
      stimulation involves a tyrosine kinase dependent step. Induction of GM-CSF may
      play a role in the initiation and perpetuation of gastric inflammation in H.
      pylori infection.

PMID- 9187878
TI  - Confirmation of nitric oxide synthesis in active ulcerative colitis by infra-red
      diode laser spectroscopy.
AB  - BACKGROUND: The synthesis of nitric oxide (NO) in the colonic mucosa of patients
      affected by ulcerative colitis (UC) has been previously investigated using
      indirect measurements of enzyme activity and non-specific measurements of luminal
      NO gas. The aim of this study was to determine unequivocally if luminal NO gas in
      active UC is present in greater concentrations than in healthy control subjects.
      METHODS: Luminal gas was collected from eight patients with active UC and eight
      healthy volunteers. NO gas concentration was measured using diode laser
      spectroscopy. RESULTS: NO gas was detected in four of eight patients with active
      UC (range 0.13-1.1 nmol) and none of the healthy control subjects. CONCLUSION: NO
      gas is present in greater concentrations in patients with active UC than in
      control subjects. This supports the view that mucosal NO synthesis is increased
      in ulcerative colitis.

PMID- 9187877
TI  - Helicobacter pylori-human polymorphonuclear leucocyte interaction in the presence
      of ammonia.
AB  - OBJECTIVE: To determine if the ammonia produced by Helicobacter pylori affects
      the phagocytic ability of human polymorphonuclear leucocytes as measured by the
      oxidative burst. METHODS: Interactions between opsonized urease-positive and 
      negative strains of H. pylori with polymorphonuclear leucocytes were studied in
      two series of experiments. In the first series of experiments, concentrations
      from 0 to 50 mM of NH4Cl were added to polymorphonuclear leucocytes. In the
      second series of experiments, bacteria were pre-incubated for 1 h with urea (0 to
      50 mM) before addition of phagocytes. Luminol-dependent chemiluminescence was
      measured every 5 min over a 50-min period. The pH was verified in each treatment.
      RESULTS: Inhibition of chemiluminescence, increasing with concentration, was
      noted in all treatments when NH4Cl was added. When urea was added to urease
      positive strains, chemiluminescence was significantly reduced when compared to
      the urease-negative strain and the zymosan control. This effect could not be
      attributed to a change in pH in the experiments using NH4Cl or urea at a
      concentration of 5 mM and 10 mM. CONCLUSION: Ammonia generated by H. pylori may
      contribute to the decreased activity of polymorphonuclear leucocytes in vivo.

PMID- 9187879
TI  - Endoscopic bile duct stent placement as a predictor of outcome following
      endoscopic sphincterotomy in patients with suspected sphincter of Oddi
      dysfunction.
AB  - OBJECTIVES: To determine whether symptomatic improvement following placement of
      endoscopic stent across the biliary sphincter could predict the longer-term
      clinical outcome after endoscopic sphincterotomy (ES). METHODS: Twenty-three post
      cholecystectomy patients with suspected sphincter of Oddi dysfunction underwent,
      sequentially, sphincter of Oddi manometry, endoscopic stent placement, ES, and
      follow-up for a further 6-12 months. RESULTS: Eight (35%) patients either did not
      respond (n = 5), did not tolerate the stent (n = 1) or relapsed during stenting
      (n = 2). Only the patient who did not tolerate the stent from the outset (12%)
      improved after ES. Of five patients who responded to stenting and had ES within 8
      weeks, only two (40%) remained asymptomatic. In contrast, of 10 patients who were
      pain-free during 12-14 weeks of stenting, nine (90%) continued to be asymptomatic
      after ES. All seven patients with an elevated sphincter of Oddi pressure
      responded to stenting and six benefited from sphincter ablation. Five (31%) of 16
      patients who had normal sphincter pressure and had improvement after 12-14 weeks
      of stenting remained free from pain following ES. ES resulted in long-term
      freedom from pain in 12 of the 23 patients: six of the seven patients with
      elevated sphincter of Oddi pressure and six of the 16 subjects with normal
      manometry (P < 0.05). CONCLUSION: Freedom from symptoms during at least 12 weeks
      of stenting predicted a favourable outcome after ES, irrespective of sphincter of
      Oddi pressure. Patients who failed to improve or showed improvement only with
      short-term stenting were less likely to benefit.

PMID- 9187880
TI  - Membrane cholesterol content of cholesterol/phospholipid vesicles determines the
      susceptibility to both damage and protection by bile salts: implications for bile
      physiology.
AB  - OBJECTIVES: To investigate the effect of membrane lipid composition on the
      susceptibility to bile salt damage and protection. DESIGN: Artificial model
      cholesterol/phospholipid (c/p) membranes (vesicles) with a varying cholesterol (0
      15 mM) and phospholipid content (3-30 mM), and with a c/p ratio ranging up to
      1.70, were prepared by sonication. We examined the effect of incubation with
      increasing concentrations of either tauroursodeoxycholate (TUDC), taurocholate
      (TC) or taurodeoxycholate (TDC) alone, or with proportionally varying mixtures of
      TUDC and TDC. METHOD: Vesicle integrity was assessed by the change in optical
      absorbance at 340 nm. RESULTS: Absorption of the bile salt-vesicle mixture
      decreased, with increasing bile salt concentration and hydrophobicity: TUDC less
      than TC less than TDC. Moreover, bile salt-induced damage also depended on
      membrane composition: vesicles containing more than 5 mM cholesterol and with a
      c/p ratio greater than 0.8 were less likely to be solubilized by 30 mM bile salt.
      Similarly, only in cholesterol-rich vesicles (c/p > 0.5) was a protective effect
      of TUDC against membrane disruption by TDC revealed upon incubation with various
      TUDC/TDC mixtures. CONCLUSION: Apart from the bile salt concentration and
      hydrophobicity, the cholesterol content of vesicles is pivotal, both in the bile
      salt-induced solubilization of cholesterol/phospholipid vesicles and in the
      potency of TUDC to prevent this.

PMID- 9187881
TI  - Quality of life in patients stented for malignant biliary obstructions.
AB  - BACKGROUND/AIMS: Endoscopic stent placement is the standard treatment for
      patients with extrahepatic malignant biliary strictures (EMBS) who are too frail
      to undergo surgical resection. Stenting relieves jaundice and pruritus but the
      effects upon other systemic symptoms and quality of life (QOL) are not known.
      METHODS: Forty-seven patients (age: 46-89 years) with jaundice due to EMBS
      completed the European Organisation for Research and Treatment of Cancer QOL
      questionnaire, EORTC QLQ-C30, and two further questions assessing jaundice and
      pruritus, at the time of diagnosis and 1 month after endoscopic stenting. Thirty
      eight patients successfully completed the study; nine patients succumbed to their
      illness within a month. RESULTS: No significant difference was found in the
      baseline QOL measurements and liver function tests between those patients who
      completed the study and those who were either too weak to answer the
      questionnaire or died within the first month of stenting. For patients who
      successfully completed follow-up, liver function tests (apart from serum albumin)
      improved after stenting. They also reported significant improvement in emotional,
      cognitive and global health scores (P < 0.01). In addition to the expected
      improvement in pruritus and jaundice (P < 0.01), anorexia, diarrhoea and sleep
      pattern were also reported to be improved (P < 0.01). CONCLUSION: Endoscopic
      stent insertion considerably improves a range of symptoms and enhances quality of
      life.

PMID- 9187882
TI  - Poor prognosis and limited therapeutic options in patients with Budd-Chiari
      syndrome and portal venous system thrombosis.
AB  - OBJECTIVES: Therapeutic options in Budd-Chiari syndrome (BCS) are highly
      dependent on the site and extent of hepatic vein thrombosis. The aim of this
      study was to evaluate the effect of additional portal venous system thrombosis on
      the clinical presentation, treatment and outcome in patients with BCS. PATIENTS:
      Clinical notes of 51 patients with BCS admitted to our centre were evaluated. We
      identified 13 patients (25%) with BCS and additional portal venous system
      thrombosis. Ten patients were female and three male with a mean age at
      presentation of 42 years (range 32-67). RESULTS: An underlying haematological
      aetiology was identified in 10 of the 13 patients. Only four patients (31%) were
      anticoagulated before referral to our centre. In addition to hepatic vein
      thrombosis seven patients had portal vein thrombosis (PVT), three had PVT,
      splenic vein (SV) and superior mesenteric vein (SMV) thrombosis and three had
      either SV, SMV or inferior vean cava (IVC) thrombosis. The presentation was acute
      in three patients, subacute in six and chronic in four with a high incidence of
      encephalopathy (6/13; 46%). Treatment included liver transplantation (four),
      mesoatrial shunt (one) and balloon dilatation of hepatic veins (two). Six
      patients were treated medically as all other options were considered too risky or
      technically impossible. Nine of 13 patients (70%) died either after surgery or
      before any treatment could be instituted (median survival 1 month), compared to
      14/38 (37%) in patients with isolated hepatic vein thrombosis (median survival
      6.3 years). CONCLUSION: We conclude that patients with BCS and portal venous
      system thrombosis constitute a unique group with limited therapeutic options and
      poor prognosis. The importance of early recognition and anticoagulation of
      patients with BCS is emphasized.

PMID- 9187883
TI  - In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in
      chronic active hepatitis C.
AB  - OBJECTIVE: Beside the hypothesis of a direct viral cytopathy, several lines of
      evidence argue in favour of hepatic damage triggered by immune-mediated
      mechanisms in hepatitis C virus (HCV) infection. The intrahepatic localization of
      HCV antigen-specific cytotoxic T-lymphocytes (CTLs) to disease sites has been
      described; however, very few data are available about the degree and the role of
      hepatic-infiltrating natural killer (NK) cells in chronically HCV-infected
      subjects. DESIGN: In a series of percutaneous needle liver biopsies obtained from
      35 consecutive untreated patients with chronic active hepatitis C, we performed
      an in-situ immunophenotyping study to evaluate the degree of cytotoxic NK cell
      infiltration as compared to CTLs, the hepatocyte expression of human major
      histocompatibility complex antigens class I and class II (HLA-I and HLA-II), and
      cell adhesion molecules (CAM) in the context of liver inflammatory infiltrates.
      The data were correlated with the histological activity index (HAI) of disease.
      RESULTS: In-situ immunophenotyping analysis of CAM provided evidence for the
      intrahepatic expression of leucocyte adhesion molecules (CD11a and CD2) and their
      corresponding ligands on hepatocytes (CD54 and CD58) in all cases. A significant
      parallel expression of CD11a and CD54 as well as CD2 and CD58 structures,
      restricted to hepatic lobules within the disease sites, was also observed, even
      if their induction exhibited different degrees of correlation with biological
      and/or histological activities. A membranous pattern of HLA-I and HLA-II antigen
      expression on hepatocyte clusters was found in all tissue samples, although HLA-I
      expression was significantly higher than HLA-II. Moreover, lymphocyte subset
      analysis displayed a CD8+ T-cell lobular infiltration within inflammatory and/or
      spotty necrosis areas in all cases, while CD4+ T-cells were confined to the
      portal and periportal levels. A few scattered CD56+ and CD16+ NK cells, mainly
      distributed at periportal areas within inflammatory and/or necrotic foci, were
      detected in 7/35 (20%) and in 5/35 (14.2%) cases, respectively. On the other
      hand, CD8+ T-cell lobular expression exhibited a linear correlation with HAI (r:
      0.698, P < 0.01). Finally, cytotoxic cell infiltration degree did not correlate
      with HCV serotypes. CONCLUSION: Our findings suggest a limited role for NK cells
      in the immune mechanism of liver injury in chronic active hepatitis C, while
      providing further support for the involvement of CD8+ T-cells at disease sites.

PMID- 9187884
TI  - Liver iron influences the response to interferon alpha therapy in chronic
      hepatitis C.
AB  - OBJECTIVE: To define whether there is any relation between the iron status of
      patients with hepatitis C virus (HCV) chronic liver disease and their response to
      interferon therapy. DESIGN: To evaluate the long-term response to 1 year of
      interferon therapy with addition of phlebotomies after 3 months of treatment if
      at that time alanine aminotransferase (ALT) had not normalized in a group of
      patients with HCV-positive chronic liver disease whose iron status had been
      characterized. SETTING: A northern Italian hospital. PARTICIPANTS: Fifty-eight
      anti-HCV-positive patients (four HCV-RNA negative) with biopsy proven chronic
      hepatitis and no evidence of iron overload as indicated by normal transferrin
      saturation at the time of enrollment in the study. INTERVENTION: Three times a
      week intramuscular injection of alpha interferon 3 MU for 1 year with addition of
      phlebotomies (350 ml/week) till iron depletion if after 3 months of interferon
      therapy ALT had not normalized. RESULTS: A long-term response was observed in 19
      of the 52 patients who completed the treatment, four HCV-RNA negative and 15
      positive. The four RNA-negative and seven of the 15 RNA-positive long-term
      responders had been treated with interferon alone, and the other eight also with
      phlebotomies. At univariate analysis only HCV genotype, gamma
      glutamyltranspeptidase and liver iron concentration were significantly associated
      with response whereas sinusoidal iron deposition was of borderline significance.
      No association was found with sex, age, duration of disease, histology, Knodell
      score, transferrin saturation %, serum ferritin, hepatocytic iron score, and
      portal iron score. HCV-RNA serum levels, measured in 29 patients, did not
      correlate with response. At multivariate analysis liver iron concentration was
      still significant and one unit reduction of liver iron concentration (natural
      logarithm transformed) was associated with 2.95 odds ratio of response.
      CONCLUSION: These results indicate that iron in the liver is more closely related
      to response to interferon than the other variables considered, including HCV
      characteristics.

PMID- 9187885
TI  - Detection of insulin-like growth factor-I and transforming growth factor-beta in
      whole gut lavage fluid: a novel method of studying intestinal fibrosis.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) and/or transforming growth
      factor-beta (IGF-beta), may be involved in gut fibrous strictures. METHODS:
      Concentrations of these two peptides have been measured by enzyme-linked
      immunosorbent assays (ELISAs) in whole gut lavage fluid from 57 patients, of whom
      14 had strictures of the small intestine or colon associated with Crohn's
      disease, irradiation injury, ischaemia or diverticulitis. RESULTS: IGF-I was
      detected in fluid from 11 of 14 patients with strictures, and 5 of 43 others (P <
      0.01). TGF-beta was detectable in all 57 samples and concentrations were
      unrelated to the presence or absence of strictures. CONCLUSION: Clinical studies
      of growth factors in intestinal fluid should facilitate research on intestinal
      fibrogenesis, and the diagnosis of fibrous stricturing in Crohn's disease.

PMID- 9187887
TI  - The roles of excessive gastro-oesophageal reflux, disordered oesophageal motility
      and decreased mucosal sensitivity in the pathogenesis of Barrett's oesophagus.
AB  - Barrett's oesophagus is often considered an end stage of gastro-oesophageal
      reflux disease. In its pathogenesis increased oesophageal acid exposure,
      disturbed oesophageal motility and decreased oesophageal mucosal sensitivity are
      thought to be of importance. In this review the role of each of these factors
      will be discussed and an update of the recent literature will be given.

PMID- 9187886
TI  - Efficacy of a pectin-based anti-reflux agent on acid reflux and recurrence of
      symptoms and oesophagitis in gastro-oesophageal reflux disease.
AB  - OBJECTIVE: Gastro-oesophageal reflux disease may be treated with a drug forming a
      floating neutral raft in the stomach. The pectin-based raft-forming anti-reflux
      agent Aflurax (Idoflux) was examined, first regarding reduction of oesophageal
      acid exposure, and next as to its efficacy as maintenance treatment in patients
      with healed oesophagitis. DESIGN: Double-blind, placebo-controlled randomized
      clinical trials. SETTING: Open access endoscopy unit. PARTICIPANTS: Fourteen
      patients with erosive oesophagitis had measurement of acid exposure. Eighty-eight
      patients with healed erosive/ulcerative oesophagitis and relief of heartburn
      after pre-treatment with omeprazole received maintenance treatment.
      INTERVENTIONS: Crossover 12-h oesophageal pH monitoring during Aflurax/placebo
      treatment. Maintenance treatment for up to 6 months with two tablets of Aflurax
      1200 mg or placebo four times daily. MAIN OUTCOME MEASURES: Percentage time pH
      less than 4 in 6 plus 6 h (upright + supine). Time to recurrence of moderate or
      severe heartburn (life table analysis). RESULTS: The median (interquartile range)
      acid exposure times in the upright position were: 3.1% (1.6-13.0%) on Aflurax
      versus 6.7% (2.5-14.9%) on placebo (P = 0.10). In the supine position no
      difference was found (Aflurax 13.7%, placebo 13.2%). The time to recurrence of
      heartburn with Aflurax treatment was prolonged significantly; after 6 months the
      life table estimates were 48% of patients in remission on Aflurax versus 8% on
      placebo (P = 0.01). Following treatment, erosive oesophagitis was found in 17/34
      on Aflurax versus 28/38 on placebo (P < 0.05). CONCLUSION: Aflurax significantly
      delays recurrence of moderate or severe heartburn and erosive oesophagitis, when
      used as maintenance treatment. The acid exposure was not significantly reduced
      with pH monitoring.

PMID- 9187888
TI  - Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: a
      promising alternative.
AB  - Recurrent bleeding from an obscure gastrointestinal source is a common but often
      frustrating clinical challenge. Frequently these bleeds can be attributed to
      vascular anomalies in the upper or lower gastrointestinal tract. Traditional
      management has included surgical resection and endoscopic fulguration. However,
      these methods are often ineffective when vascular lesions are diffuse, difficult
      to identify, or endoscopically inaccessible. Hormone therapy with a combination
      of oestrogen and progesterone represents a promising alternative. Since initial
      reports of success in patients with epistaxis from hereditary haemorrhagic
      telangiectasia, growing evidence supports its role in reducing bleeding from
      gastrointestinal vascular anomalies. Existing literature is critically reviewed
      and management strategies incorporating hormone therapy are suggested.

PMID- 9187889
TI  - Consensus or confusion: a review of existing national guidelines on Helicobacter
      pylori-related disease.
AB  - Since the discovery of Helicobacter pylori, a considerable amount of progress has
      been made in our understanding of H. pylori-related conditions. However,
      considerable confusion exists in relation to the optimal application of these
      findings to clinical practice, particularly at a primary care setting. In the USA
      the National Institutes of Health published guidelines outlining the role of H.
      pylori in peptic ulcer disease in 1994. Since then at least eight European
      countries have issued guidelines. The differences that exist between these
      documents reflect the rapid evolution of opinion on how the diagnosis and
      treatment of H. pylori should influence the traditional management of conditions
      presenting with dyspepsia. It is clear that little controversy surrounds the
      approach to duodenal and gastric ulceration. Patients with gastric mucosa
      associated lymphoid tissue lymphoma need careful follow-up. The greatest level of
      disagreement exists in relation to the management of non-ulcer dyspepsia and
      dyspepsia in the community. These areas, in addition to the role of H. pylori
      eradication when non-steroidal antiinflammatory drugs or long-term acid
      suppressor are considered, need further evaluation. Most countries now recommend
      proton pump-based triple therapy regimes as first-line treatment for the
      eradication of H. pylori.

PMID- 9187890
TI  - Eosinophilic gastroenteritis.
AB  - Eosinophilic gastroenteritis is a rare disease of unknown aetiology characterized
      by eosinophilic infiltration of the gastrointestinal wall and increased
      peripheral blood eosinophilia. The frequent finding of concomitant extradigestive
      involvement calls for differential diagnosis to distinguish some multisystemic
      pathologies, such as connective tissue disease. We recently treated a young woman
      affected by eosinophilic infiltration of the small and large intestine which
      spread to other organs. Tests ruled out allergic or parasitic aetiopathogenesis
      of the disease. The clinical, biological and evolutive findings suggest that
      eosinophilic gastroenteritis may evolve into idiopathic hypereosinophilic
      syndrome.

PMID- 9187891
TI  - Diagnostic use of endoscopic mucosal resection.
AB  - We report two cases of gastric carcinoma where repeated, multiple conventional
      endoscopic biopsies were falsely negative. Endoscopic mucosal resection gave a
      positive diagnosis in both these patients. New equipment for aspiration
      mucosectomy makes the technique easier to perform, and a larger, deeper biopsy is
      obtained.

PMID- 9187892
TI  - Tonsillectomy and inflammatory bowel disease location.

PMID- 9187893
TI  - Ranitidine in a twice daily triple therapy regimen for the eradication of
      Helicobacter pylori.

PMID- 9187894
TI  - Free/total prostate-specific antigen ratio--hope and controversies.
AB  - Prostate-specific antigen (PSA) forms in serum two stable complexes with alpha 1
      antichymotrypsin and alpha 2-macroglobulin. PSA complexed to alpha 1
      antichymotrypsin is the predominant fraction of PSA. A minor fraction of serum
      PSA is not associated with proteinase inhibitors. These molecular differences
      explain the possibility to distinguish free from total PSA (F/T ratio). Free and
      complexed PSA have different clearances and significant differences between
      clearance of free PSA after radical prostatectomy (RP) and after open surgery for
      benign prostatic hyperplasia (BPH) are observed. These differences are explained
      by the entire removal of prostatic cells responsible for PSA synthesis and
      storage during RP, i.e. the source of free PSA present in the intravascular pool.
      The proportion of free PSA is significantly lower in patients with prostate
      cancer than in patients with BPH. Thus, the mean F/T ratio in prostate cancer is
      lower than that in BPH and may be helpful to distinguish cancer from BPH
      especially in the gray zone of total PSA (4-10 ng/ml). The reason why complexed
      PSA increases in patients with prostate cancer remains unknown but could be
      explained by the requirement of an enzymatically active PSA released by the
      malignant prostate tissue to bind to alpha 1-antichymotrypsin. However, a
      consensual threshold value for L/T ratio is yet to be found to be of widespread
      clinical use in the differential diagnosis between cancer and BPH.

PMID- 9187895
TI  - Endopyelotomy with the Acucise cutting balloon device. Early clinical experience.
AB  - OBJECTIVES: To evaluate the efficacy of the Acucise balloon cutting device in the
      treatment of ureteropelvic junction (UPJ) stenosis. METHODS: Forty-four patients
      with primary (21) or secondary (23) UPJ stenosis underwent Acucise endopyelotomy
      between July 1992 and February 1995. RESULTS: The average operating time was 53
      min and the average hospital stay was 6 +/- 4 days. The follow-up schedule
      included a symptom questionnaire, intravenous urography and diuretic renal scan.
      Of the 44 patients, 38 have been followed for a minimum of 3 months
      postoperatively (mean: 12 months, range: 3-39 months). Overall success was
      achieved in 29 (76%). The procedure was successful in 16 out of 19 cases (84%)
      with secondary strictures. When the technique was used for the treatment of
      primary UPJ strictures, the success rate was only 68% (13 out 19). The presence
      of a large periureteric urinoma was identified as the cause of failure in 2 cases
      of primary strictures. CONCLUSION: We recommend the use of the Acucise device as
      the first-line therapy for treatment of secondary UPJ stenosis (except in the
      presence of large enclosed stones). We do not approve the use of the Acucise
      device for treatment of primary UPJ strictures. In primary hydronephrosis, the
      negative role of periureteric extravasation probably explains the low success
      rate of 68% (as opposed to 85% for a large series of percutaneous
      endopyelotomies.

PMID- 9187896
TI  - Use of slings made of indigenous and allogenic material (Goretex) in type III
      urinary incontinence and comparison between them.
AB  - OBJECTIVE: To evaluate the use of Goretex pubovaginal sling and compare the
      results with a typical indigenous material graft made of rectal fascia. METHODS:
      We have prospectively evaluated 48 consecutive patients in a randomized fashion
      in whom a sling procedure was performed to treat their type III incontinence.
      Sixteen women had a vesicourethral suspension (VUS) by a Goretex sling and
      another group of 32 patients, comparable in age range and medium age with the
      previous group, had a similar VUS by a sling from the rectus abdominis fascia.
      Both groups were evaluated urodynamically 6 and 30 months later. RESULTS: In the
      first group, cure of incontinence was observed in 87.5% and in the remaining
      patients it was significantly improved. In 2 patients there was an erosion of the
      urethra and the Goretex sling had to be removed 3.5 years later. Three other
      women remained dry but complained of occasional irritative symptoms. In the
      remaining 11 there was no erosion and the excellent postoperative result was
      maintained. In the group with fascial slings there was no erosion observed and in
      general they had less irritative symptoms. Cure or improvement of incontinence
      was comparable with the first group when studied 6 months after surgery, but
      there was a significant difference in the 30 months postoperative evaluation.
      CONCLUSIONS: Use of a Goretex sling provides better long-term results even though
      it is associated with somewhat increased morbidity.

PMID- 9187897
TI  - Primary testicular seminoma: prognostic significance of nuclear DNA ploidy
      pattern.
AB  - OBJECTIVE: To evaluate the impact of nuclear DNA content on outcome of patients
      with testicular seminoma. METHODS: Formalin-fixed paraffin-embedded blocks taken
      from 111 patients with primary testicular seminoma were studied by flow cytometry
      for nuclear DNA content. The results of ploidy status were correlated with
      histopathologic features, tumor progression and patients' survival. RESULTS: 48%
      of the tumors were DNA diploid and 52% were DNA aneuploid. None of the patients
      with DNA diploid seminoma had an advanced stage seminoma at the time of
      diagnosis. Progression after therapy or cancer-related death occurred only in
      patients who had DNA aneuploid testicular tumors. CONCLUSIONS: Nuclear DNA ploidy
      pattern provides important prognostic information for patients with testicular
      seminoma.

PMID- 9187898
TI  - Phase II study: adjuvant single-agent carboplatin therapy for clinical stage I
      seminoma.
AB  - OBJECTIVE: Though para-aortal and ipsilateral iliacal radiation is the
      established adjuvant treatment for clinical stage I seminoma, promising results
      have been reported on adjuvant single-agent carboplatin therapy. PATIENTS AND
      METHODS: We treated 43 patients with clinical stage I seminoma according to this
      option. They received 2 courses of single-agent carboplatin (400 mg/m2) at an
      intervall of 3 weeks. Therapy could be performed on an outpatient basis within 2
      h. RESULTS: Therapy was well tolerated. Apart from minor gastrointestinal
      disorders and mild myelosuppression, no adverse reactions were observed. The
      median follow-up is 28 months. Up to now no recurrences have been noted.
      CONCLUSIONS: If the recurrence rate remains as low as after adjuvant
      radiotherapy, which should be proved in a phase III study, single-agent
      carboplatin therapy will be an alternative adjuvant approach for clinical stage I
      seminoma.

PMID- 9187899
TI  - Elevated human chorionic gonadotropin concentrations in the testicular vein and
      in peripheral venous blood in seminoma patients. An analysis of various
      parameters.
AB  - OBJECTIVE: Human chorionic gonadotropin (HCG) elevations in the testicular vein
      (TV) are correlated with those in the cubital vein (CV). Their significance was
      tested regarding various prognostic parameters. METHOD: Within the framework of a
      large multicentre study to assess the prognosis of HCG-positive seminomas 726
      eligible patients were recruited from 1986 to 1991. A total of 378 had elevated
      and 348 had normal HCG measured in the CV. In 144 patients samples were taken
      from the TV. Histological diagnosis of seminoma was confirmed by two reference
      pathologists. Three groups (group I: elevated HCG in CV and normal or elevated
      HCG in TV; group II: normal HCG in CV and elevated HCG in TV; group III: normal
      HCG in CV and normal or unknown HCG in TV) were compared in relation to the
      presence or absence of metastases, stage of the disease, size of the primary
      tumour, pT category, vascular invasion and lactate dehydrogenase. RESULTS: Of the
      TV serum samples, 85% were HCG-positive. Regression analysis revealed higher
      values in the TV compared to the CV according to the following equation: HCGTV =
      520 + 1.12 x HCGCV, R = 0.766, with a mean variation of 14%. Patients in group I
      had significantly higher stages and larger primary tumours than patients with
      normal HCG in the CV, irrespective of the HCG values in the TV blood (groups II
      and III). Therefore, HCG is associated with tumour mass. No differences of
      statistical significance were found regarding T category, vascular invasion and
      lactate dehydrogenase. There were no differences between groups II and III.
      CONCLUSION: Only HCG values of the CV are associated with known adverse
      prognostic factors of seminomas, such as metastases and size of the tumour. HCG
      in the TV adds no further information for the clinical assessment of patients
      with seminoma.

PMID- 9187900
TI  - Toxicity and results of MVAC (methotrexate, vinblastine, adriamycin and
      cisplatin) chemotherapy in advanced urothelial carcinoma.
AB  - OBJECTIVE: The experience with MVAC (methotrexate, vinblastine, Adriamycin and
      cisplatin) chemotherapy in advanced urothelial cancer is reviewed with emphasis
      on toxicity and efficacy. METHODS: We report on 28 patients with advanced,
      progressive transitional cell carcinoma (TCC) of the bladder (27) or ureter (1),
      treated with MVAC. RESULTS: The average number of cycles was 4.5. Leucopenia was
      the most frequent and severe side effect (18% WHO grade I, 46% GII, 19% GII and
      4% GIV). Other side effects were acceptable and could be treated successfully.
      One patient (complete responder) died of a toxic cause (sepsis), a second patient
      (partial responder) died of an intestinal bleeding (not drug- or cancer-related).
      Complete response was seen in 10 patients (36%), partial response and stable
      disease in 4 patients each (14%), progression in 8 patients (29%), and 2 patients
      were not evaluable for response. However, relapses were frequent (8 of 12
      remaining responders, 66%). Median survival of the whole group was 9 months (0
      52), without a significant difference for responders and nonresponders (p =
      0.29). CONCLUSION: Our results are comparable to data from the literature with
      regard to efficacy and toxicity, although detailed toxicity data are
      unfortunately not always available.

PMID- 9187901
TI  - Chemotherapy with methotrexate, vinblastine, epirubicin and carboplatin (Carbo
      MVE) in transitional cell urothelial cancer. A Hellenic Co-Operative Oncology
      Group study.
AB  - OBJECTIVES: We conducted a phase II study in order to assess the efficacy and
      toxicity of Carbo-MVE (carboplatin 250 mg/m2 i.v. day 1, methotrexate 25 mg/m2
      i.v. days 1, 15 and 22, vinblastine 2.5 mg/m2 i.v. days 1, 15 and 22 and
      epirubicin 25 mg/m2 day 1). The regimen ws to be repeated every 28 days. METHODS:
      Forty-six patients with transitional cell carcinoma of the bladder entered the
      study. Patients with metastatic disease were treated for 6 cycles, while patients
      with locally advanced or locoregional disease had 4 cycles of induction
      chemotherapy followed by cystectomy or radiotherapy. RESULTS: Toxicity was
      generally mild and treatment well tolerated. The overall response rate was 54.4%,
      with 26% complete and 28.3% partial response rates. The median survival was 17.5
      months with the complete responders to live significantly longer (64.82 months)
      than those who had a partial response (20.5 months), stable disease (15 months)
      or progressive disease (8.5 months). Survival was also significantly longer in
      patients with good performance status as well as in patients with locally
      advanced or locoregional disease. Finally, patients who had cystectomy as
      definitive treatment survived significantly longer (32 months) than those who had
      been irradiated (16 months). CONCLUSIONS: The Carbo-MVE regimen appears to be an
      effective and well-tolerated treatment in patients with transitional cell
      carcinoma of the bladder.

PMID- 9187902
TI  - Human papillomavirus 16 and 18 infection is absent in urinary bladder carcinomas.
AB  - OBJECTIVE: The role of human papillomavirus (HPV) in the pathogenesis of bladder
      neoplasia remains controversial. Studies to date have mainly utilized polymerase
      chain reaction and DNA blot techniques to detect HPV DNA. The detection rates
      have varied from 0 to 81%. One of the major limitations of these techniques is
      that they lack topographic information. We have used a highly sensitive in situ
      hybridization (ISH) technique which detects single copies of viral genome and
      provides topographic information for investigation of HPV infection in bladder
      carcinomas. MATERIALS AND METHODS: Thirty-one samples of formalin-fixed paraffin
      embedded bladder carcinomas (4 adenocarcinomas, 5 squamous cell and 22
      transitional cell carcinomas) were examined using non-isotopic ISH with biotin
      labelled DNA probes of HPV 16 and 18 subtypes. HPV-positive skin and anal
      carcinoma samples were used as controls. RESULTS AND CONCLUSIONS: No positive
      signals for HPV 16 or 18 were detected in any of the bladder carcinoma samples.
      Given the sensitivity of the technique, the result indicates that HPV 16 and 18
      are not implicated in the development of bladder neoplasia compared to certain
      other epithelial malignancies. The possibility that other subtypes of HPV
      contribute to bladder epithelial carcinogenesis remains to be clarified.

PMID- 9187903
TI  - Urological complications in renal transplantation. A comparison between living
      related and cadaveric grafts.
AB  - OBJECTIVE: Since 1989 the percentage of living-related donor renal
      transplantations has increased considerably at our institution. We compared the
      incidence of urological complications in the living-related donor transplantation
      (LRDT) group and the cadaveric donor transplantation (CDT) group. METHODS:
      Between September 1989 and September 1994, 534 consecutive patients underwent a
      renal transplantation. During that period, the percentage of LRDT increased from
      10 to 25 (mean: 14.8) per year. In all patients a transvesical
      ureteroneocystostomy without antireflux mechanism was performed. RESULT: A
      urological complication developed in 64 (11.9%) of the recipients (obstruction in
      6.3%; leakage in 5.6%). In 41 (7.7%) patients the complication was transitory and
      could be managed with minimal invasive measures such as a percutaneous
      nephrostomy (n = 34), drainage of a paraurethral fluid collection (n = 13),
      transurethral bladder drainage (n = 3) or a combination of these. In 23 (4.3%) of
      the recipients a secondary urological intervention such as a pyeloureterostomy (n
      = 21) or percutaneous dilatation of a ureteral stricture was necessary. The
      incidence of obstruction was equal in the LRDT and CDT groups, whereas leakage
      was more frequently encountered in the LRDT group (11.4 vs. 4.6%, p < 0.05).
      Transplant survival after 1 year was significantly better in the LRDT group than
      in the CDT group (97 vs. 77%, p < 0.001). CONCLUSION: The risk of leakage is
      higher in living-related donor kidney transplantations. Urological complications,
      however, do not impair graft survival.

PMID- 9187904
TI  - Failed vasectomy reversal: is a further attempt worthwhile using microsurgery?
AB  - OBJECTIVES: Following surgery for vasectomy reversal there is a substantial
      failure rate in achieving fertility. Obstruction at the anastomotic site is the
      cause in the majority of cases. Further exploration to reconstruct the
      anastomosis using no magnification or a magnifying loupe can be difficult and
      even impossible, and can result in further failure, especially if the convoluted
      part of the vas had been involved. The outcome of revision by a microscopic
      technique of vasovasostomy was thus investigated. METHODS: A meticulous
      microsurgical technique employing a 2-layer interrupted suture, end-to-end
      anastomosis with 10/0 nylon, was used to establish continuity of the lumen.
      RESULTS: Sperm in the ejaculate was achieved in 64% of 22 patients operated on
      after previous failure. Fertility rate after a mean follow-up of 23 months (range
      8 months to 6 years) demonstrated by pregnancy in their partners has occurred so
      far in 27%. Length of the obstructive period was related to the outcome as well
      as the presence or absence of sperm at operation, but neither of these indicators
      or the presence of antisperm antibodies comprised a bar to eventual success.
      CONCLUSION: Microsurgical vasovasostomy after previous failure provides the
      patient with further reasonable hope of success in becoming fertile, but
      microsurgical skills are required.

PMID- 9187905
TI  - Sacral rhizotomies and electrical bladder stimulation in spinal cord injury. 2.
      Cost-effectiveness and quality of life analysis. Dutch Study Group on Sacral
      Anterior Root Stimulation.
AB  - OBJECTIVES: To present a cost-effectiveness analysis of sacral rhizotomies and
      electrical bladder stimulation compared with conventional care of neurogenic
      bladder dysfunction in patients with spinal cord injury. METHODS: During a 3-year
      inclusion period, data on costs and quality of life before the intervention were
      collected to describe conventional care. Data on the pre-implantation period, the
      implantation and a follow-up period of 2 years were collected following a strict
      protocol simultaneous with medical and urodynamic data and were used to calculate
      the costs and effects on quality of life of the implantation of the stimulator.
      RESULTS: Between June 1991 and June 1994, 52 patients with complete cervical or
      thoracic spinal cord lesions underwent sacral posterior rhizotomies and
      implantation of a Finetech-Brindley sacral anterior root stimulator. Although the
      initial costs of sacral anterior root stimulation are high, they are earned back
      in this series in about 8 years after the implantation. General indicators of the
      quality of life show no significant changes after the implantation. Factors
      related to psychological well-being and the patients' satisfaction with the
      emptying of the bladder increased significantly whereas the experienced problems
      of micturition and incontinence all decreased significantly. CONCLUSION: Sacral
      rhizotomies and electrical bladder stimulation make a cost-effective method of
      treatment of lower urinary tract dysfunction in patients with spinal cord injury.
      Considerable savings on health care costs are possible in the long run with
      simultaneous positive effects on aspects of health status.

PMID- 9187906
TI  - The uroflowmetry in normal men and after prostatectomy.
AB  - OBJECTIVE: This study was designed to determine and compare the uroflow
      parameters of normal men and patients after prostatectomy in order to investigate
      the flow rate expression in men without bladder outlet obstruction. MATERIALS AND
      METHODS: Five hundred and fourteen men aged from 17 to 84 years who subjectively
      felt that their urination was normal and were objectively demonstrated to be
      without prostatic hyperplasia were enrolled in the normal group. For comparison,
      356 patients after prostatectomy were also included as age-matched treated
      groups. Both groups were further divided into age-based subgroups. Uroflowmetry
      and transrectal sonography were performed in all the subjects. The uroflow
      parameters and prostatic volumes of different patient groups were compared.
      Regression analysis was used to estimate the correlation between maximal flow
      rate (Qmax) and age, as well as between Qmax and volume. RESULTS: The results
      show that voided volume decreased with age in asymptomatic men without prostatic
      hyperplasia. The decreased voided volume with age resulted in declining Qmax in
      normal men. In patients after prostatectomy, however, infravesical obstruction
      affected detrusor contractility more with age and resulted in a declining flow
      rate expressed in similar voided volumes. In normal men, the mean Qmax was 20.7
      +/- 7.3 ml/s in a mean voided volume of 290.7 +/- 123.2 ml. As age increased,
      smaller bladder capacity resulted in lower flow rate expressions, but the
      corrected Qmax showed no significant differences. CONCLUSION: Normal elderly men
      without prostatic hyperplasia can have good urinary flow and good bladder
      energetics. Asymptomatic men with low flows might have incipient infravesical
      obstructions. Patients after prostatectomy had impaired detrusor contractility
      that resulted in a low flow rate expression with age.

PMID- 9187907
TI  - Etiological and clinical patterns of urolithiasis in Turkish children.
AB  - OBJECTIVE: To evaluate the clinical and etiological characteristics of childhood
      urolithiasis in Turkey. METHODS: Ninety-two children with urolithiasis were
      studied retrospectively according to clinical patterns and etiological factors
      between January 1990 and January 1995. RESULTS: The age range of the patients was
      from 2 months to 14 years (mean age 6.9 years), and there was a male/female ratio
      of 1.6. The onset of the disease was earlier in boys than in girls. The most
      striking features were the initial admission of 14 (15.2%) children after the
      development of chronic renal failure and that most of them (64.3%) had infection
      stones. The stones were localized in the upper urinary system in 68.5% of the
      patients; bladder stones were rare (10.9%). The recurrence rate at presentation
      was 15.2% in all patients. As etiological factors, an anatomical defect was found
      in 30.4% of the patients, infections in 31.5%, and metabolic disorders in 26.1%;
      11 (12.0%) of them were classified as idiopathic. The earliest presentation was
      seen with metabolic and infection stones and the highest recurrence rate (37.5%)
      in patients with metabolic stones. CONCLUSION: Childhood urolithiasis is a
      serious problem in Turkey. In order to prevent the development of end-stage renal
      failure and to improve the patients' quality of life, more efforts should be made
      with respect to early diagnosis and management of renal stones and urinary tract
      infections.

PMID- 9187908
TI  - Nocturnal enuresis and daytime wetting: a multicentric trial with oxybutynin and
      desmopressin.
AB  - OBJECTIVE: Different etiopathological mechanisms of enuresis are today under
      study, and different therapies and drugs have been proposed. The Italian
      Multicentric Trial was undertaken in twelve pediatric and urological centers in
      order to assess the efficacy of two of the most popular drugs, desmopressin
      (DDAVP) and oxybutynin. METHODS: 114 enuretic patients were enrolled in the
      study. After a 2-week observation period, 66 patients with primary
      monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally,
      for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly
      assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The
      efficacy of the two drugs was measured in terms of reduction of wet nights per
      week during the 6-week treatment period and a 2-week follow-up period. Children
      with 0-3 dry nights/week were considered as nonresponders. RESULTS: Patients with
      monosymptomatic enuresis treated with DDAVP reported a significantly lower number
      of wet night during treatment than during the baseline period, with 79% showing a
      'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of
      the patients with diurnal voiding disturbances and enuresis, those treated with
      oxybutynin alone had a 54% success rate. The patients treated with both
      oxybutynin and DDAVP showed a better response, with a 71% rate of success.
      CONCLUSIONS: The efficacy of the two drugs is confirmed in patients carefully
      selected on the clinical basis of voiding disturbances. In patients with enuresis
      and voiding dysfunction, the reduced urinary output and the lower bladder filling
      rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the
      oxybutynin action.

PMID- 9187909
TI  - p53 and c-jun expression in urinary bladder transitional cell carcinoma:
      correlation with proliferating cell nuclear antigen (PCNA) histological grade and
      clinical stage.
AB  - OBJECTIVE: To investigate p53 and c-jun oncoproteins and proliferating cell
      nuclear antigen (PCNA) in transitional cell urinary bladder carcinomas (TCCs) and
      to determine their relationships to tumour grade, stage and survival. MATERIALS
      AND METHODS: The expression of p53, c-jun and PCNA was studied using
      immunohistochemistry in formalin-fixed, paraffin-embedded tissues in a series of
      110 TCCs. RESULTS: 58% of our cases were positive for p53 and 88% for c-jun. A
      statistically very significant correlation (p < 0.0001) was observed between p53
      and c-jun (r = 0.781), p53 and PCNA (r = 0.772), c-jun and PCNA (r = 0.831) as
      well as between each of the two oncoproteins and the histological grade and
      clinical stage (p < 0.001). There was no correlation of either p53, PCNA or c-jun
      with clinical outcome in terms of patients survival. CONCLUSION: p53 and c-jun
      proteins' overexpression are strongly related to rapid tumour cell proliferation
      and hence with aggressive growth in urinary bladder TCC. PCNA score remains an
      important prognostic index in transitional cell carcinoma of the bladder.

PMID- 9187910
TI  - T lymphocytes infiltrating the bladder wall of patients with carcinoma of urinary
      bladder are in vivo activated.
AB  - OBJECTIVES: This paper studies the phenotypical characteristics of the
      lymphocytes present in mononuclear cell (MNC) preparations from peripheral blood
      (PBMNC), lymph nodes (LNMNC), tumor bladder (TBMNC), and tumor-free bladder
      (TFBMNC) from patients with infiltrated transitional cell carcinoma (TCC) of the
      bladder and PBMNC of healthy controls. METHODS: Eight patients diagnosed with TCC
      of the bladder, according to UICC criteria, and 10 healthy controls were studied.
      For immunofluorescence staining, T lymphocytes were incubated with combinations
      of fluorescein (FITC, green)- and phycoerytrin (PE, red)-labelled monoclonal
      antibodies. RESULTS: The percentage of NK cells in the LNMNC and TFBMNC was
      significantly decreased in comparison to that found in the PBMNC from these
      patients (p < 0.05). A significant enhancement of the expression of class II
      molecules of the major histocompatibility complex (MHC) by CD3+ T lymphocytes
      from TBMNC and TFBMNC specimens from bladder walls was found with respect to
      those quantified in CD3+ T lymphocytes from PBMNC (p < 0.05). In addition, the
      percentage of CD3+CD25+ T lymphocytes was significantly higher in PBMNC in TCC
      patients than in healthy controls (p < 0.05). CONCLUSIONS: Our data clearly
      demonstrate that the presence of infiltrative TCC of the bladder is associated to
      an infiltration of in vivo activated T lymphocytes of the urinary bladder wall.
      This in vivo T lymphocyte activation has been considered an expression of the
      immune response against the tumor cells.

PMID- 9187911
TI  - Epidermal growth factor family and renal cell carcinoma: expression and
      prognostic impact.
AB  - OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal
      growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS
      AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF
      R), and c-erb B-2 were determined immunohistochemically in formalin-fixed
      paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The
      prognostic significance of these growth factors and their receptors as well as of
      tumor stage and malignancy grade was examined with respect to survival and tumor
      recurrence by following up the fate of the patients after nephrectomy (mean
      follow-up time 5.2 years). RESULTS: The members of the EGF family and their
      receptors studied were expressed to a variable degree in all RCCs investigated.
      However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007)
      and malignancy grade (p < 0.007) but none of the growth factors or receptors
      studied (p > 0.05, respectively) exhibited prognostic significance with respect
      to both survival and disease-free period. On the contrary, there was a
      significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p =
      0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha
      and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03).
      The coexpression of the factors studied also showed no prognostic relevance.
      CONCLUSION: The expression of these members of the EGF family seems not to bear
      evaluable prognostic information for clinical use in the case of RCC.

PMID- 9187912
TI  - Does urinary oxalate interfere with the inhibitory role of glycosaminoglycans and
      semisynthetic sulfated polysaccharides in calcium oxalate crystallization?
AB  - OBJECTIVES: Previously it was shown that the polysaccharide G872 in vitro
      strongly inhibits calcium oxalate monohydrate crystallization processes. However,
      when rats on a stone-inducing diet of ethylene glycol plus vitamin D3 are given
      this polysaccharide, no changes in the urine capacity for crystallization
      inhibition were found. We investigated here how the inhibitory action of
      polysaccharides changes under high oxalate conditions, as they exist in the stone
      inducing diet. METHODS: Calcium oxalate monohydrate (COM) crystals were incubated
      in a series of 0.05 M PBS buffers containing polysaccharides with increasing
      oxalate concentrations (0-0.4 mmol/l). The coated crystals were collected, washed
      and resuspended in an artificial urine. We then measured the zeta potential of
      the crystals, using a Coulter DELSA 440, and the initial rates for crystal growth
      and agglomeration, using the Coulter Multisizer II. RESULTS: Addition of oxalate
      to the medium shifts the negative zeta potential distribution of COM crystals
      coated by polysaccharides in positive direction. Particle size analysis
      demonstrated that the initial rates of COM crystal growth and agglomeration
      responding to oxalate concentration changes (0.1-->0.4 mmol/l) in the presence of
      G872 (0.2 mg/l) are approximately 2.5 times faster than that in the absence of
      G872. CONCLUSIONS: Oxalate interferes with the binding of polysaccharides to
      crystals. This can be envisioned to occur through changes in the crystal surface
      properties or by induction of functional and secondary structural changes of
      urinary macromolecular inhibitors such as GAGs, resulting in a decrease of their
      inhibitory activity against COM crystallization. Thus, in urine, a high oxalate
      may increase the rate of crystallization both by increasing the supersaturation
      and by decreasing the inhibitory potential of the urine.

PMID- 9187913
TI  - Does ureteral manipulation improve the effect of extracorporeal electromagnetic
      shock wave treatment on impacted ureteral calculi?--an experimental study.
AB  - OBJECTIVE: We used an experimental study to evaluate the effects of ureteral
      manipulation on the disintegration of impacted ureteral calculi. METHODS: Fifteen
      urinary calculi were divided into 3 groups according to the type of ureteral
      manipulation. Group 1: control group, no manipulation; group 2: bypass
      catheterization, and group 3: below irrigation in porcine ureter. Each calculus
      was subjected to 500 shock wave pulses with 0.28 mJ/mm2 power density by a
      Siemens Lithostar II lithotriptor. RESULTS: The successful disintegration ratio
      for calculus sizes less than 4 and 2 mm was 79.4 +/- 13.1 and 42.2 +/- 7.5%
      (group 1), 82.3 +/- 5.2 and 43.5 +/- 2.4% (group 2) and 84.3 +/- 17.3 and 49.7 +/
      14.6% (group 3). There was no statistical difference among the 3 groups by Anova
      and the Kruskal-Wallis test. CONCLUSION: The ureteral manipulation of impacted
      ureteral calculi was unable to improve stone disintegration by shock wave.

PMID- 9187914
TI  - Laparoscopic tumorectomy for renal cell carcinoma in a HIV-positive patient.
AB  - We report on a HIV-positive patient in whom laparoscopic nephron-sparing surgery
      has been performed. A 47-year-old white male referred for evaluation and
      treatment of an asymptomatic, serendipitously discovered renal mass. The patient
      underwent a laparoscopic tumorectomy; indications, surgical technique and
      rationale are described in detail.

PMID- 9187915
TI  - Laparoscopic unroofing of adrenal cysts.
AB  - OBJECTIVES: This study was aimed to demonstrate the feasibility of laparoscopic
      conservative surgery of the adrenal gland in the treatment of adrenal cysts.
      METHODS: Two cases of laparoscopic decortication of symptomatic adrenal cysts
      with preservation of the adrenal parenchyma are presented. RESULTS: Surgery was
      uneventful in both cases and patients returned to preoperative activity within 10
      days from the operation. At the 3-month follow-up, computerized tomography
      demonstrated the absence of any cystic recurrence and adrenal endocrine function
      was normal. These findings were confirmed at the 1-year follow-up by
      ultrasonography. CONCLUSIONS: Symptomatic adrenal cysts can be effectively and
      safely treated by laparoscopic unroofing, a minimally invasive procedure which
      leaves the nondiseased adrenal parenchyma intact.

PMID- 9187916
TI  - Interaction of GPI-anchored cell surface proteins and complement receptor type 3.
AB  - Glycosylphosphatidylinositol (GPI)-anchored cell surface proteins lack
      transmembrane and cytoplasmic domains. For some of them, such as CD14, CD16b and
      CD87, it could be demonstrated recently that they are physically and functionally
      associated with complement receptor type 3 (CR3, CD11b/CD18). Also, there are
      indications that in certain cells these GPI proteins employ CR3 as an adapter for
      signal transduction across the plasma membrane.

PMID- 9187917
TI  - Human immunodeficiency virus and the complement system.

PMID- 9187918
TI  - Role of C3a and C5a in the activation of mast cells.
AB  - Mast cells and basophils are known to be triggered by allergens via cross-linking
      with their high-affinity IgE-binding receptors, Fc epsilon RI. The anaphylatoxic
      activity of the complement-derived peptides C3a and C5a has been known for a long
      time; however, it has also been reported that serosal- and mucosal-type mast
      cells respond differently to peptidergic stimuli. The mechanism of mast cell
      activation by cross-linking of Fc epsilon RI has been the subject of intensive
      studies in the past few years, while the action mode of the anaphylatoxic
      complement peptides has been revealed only recently. We report about a novel
      function of C3a: its inhibitory activity on IgE-mediated triggering of the
      mucosal RBL-2H3 cells. Surprisingly, the other anaphylatoxic peptide C5a, which
      has been shown to be significantly more effective in several biological assays,
      did not influence antigen-induced triggering of the RBL-2H3 cell line at all.

PMID- 9187919
TI  - Role of complement in inflammation and injury in the nervous system.
AB  - The complement (C) system plays important roles in host defence but activation at
      inappropriate sites or to an excessive degree can cause host tissue damage. C has
      been implicated as a factor in the causation or propagation of tissue injury in
      numerous diseases. The brain is an immunologically isolated site, sheltered from
      circulating cells and proteins of the immune system; nevertheless, there is a
      growing body of evidence implicating C in numerous brain diseases. In this brief
      article we review the evidence suggesting a role for C in diseases of the central
      and peripheral nervous system and discuss the possible sources of C at these
      sites. Some brain cells synthesise C and also express specific receptors; some
      are exquisitely sensitive to the lytic effects of C. The evidence suggests that C
      synthesis and activation in the brain are important in immune defence at this
      site but may also play a role in brain disease.

PMID- 9187920
TI  - Biocompatibility: complement as mediator of tissue damage and as indicator of
      incompatibility.
AB  - The fully biocompatible surface is the host's own intact endothelium. Blood
      contact with a damaged or foreign endothelium, or with an artificial surface,
      will lead to a certain degree of activation of the defense systems. Complement is
      one of these systems which has a unique property to distinguish between 'self'
      and 'non-self'. Recent data using complement-specific inhibitors like soluble CR1
      and monoclonal antibodies to C5 have shown that complement is not only associated
      with, but in fact contributes to, the whole body inflammatory reaction seen as a
      complication to cardiopulmonary bypass (artificial surfaces) and is responsible
      for the hyperacute rejection of xenografts (foreign endothelium). Complement
      activation, as measured by assays specific for neoepitopes exposed in the
      activation products, is a sensitive indicator of bioincompatibility. These assays
      have been increasingly important after a causal link between complement
      activation and tissue damage was demonstrated. Efforts have been made to improve
      the biocompatibility of artificial surfaces, including coating with heparin. This
      procedure not only improves coagulation compatibility, but also markedly reduces
      complement activation. Models to study complement compatibility in vitro and in
      vivo are described, and recommended complement activation assays reviewed.

PMID- 9187921
TI  - Advances in mucosal immunology.
AB  - HIV infection is likely to remain a significant medical and scientific problem
      well into the twenty-first century. During the first 15 years of the epidemic,
      much has been learned about the biology of HIV infection, but the majority of
      biomedical research has focused on the peripheral circulation. It is likely that
      the behavior of the virus within the unique immunologic environment of the
      intestinal mucosa differs from that which is observed in the periphery. Many
      clinical and epidemiologic features of HIV infection offer compelling reasons to
      encourage further examination of the mucosal immune system's role in AIDS
      pathogenesis. This article has touched on most of the significant observations
      concerning the mucosal immune system and HIV infection, and it is clear that much
      remains to be done. As mentioned earlier, the mucosal abnormalities observed in
      HIV infection are likely to have many causes. Careful evaluation of patients with
      early disease and fewer confounding variables may provide fresh insight into AIDS
      pathogenesis. Similarly, prospective evaluation of selected patient populations
      may be more informative in characterizing the progressive alterations in mucosal
      immune function than random cross-sectional studies of poorly defined groups. It
      is equally important for immunologic assessment to be correlated with nutritional
      and symptomatic evaluation. Finally, the success or failure of future
      antiretroviral therapies will be critically related to the impact of such agents
      on lymphoid reservoirs of HIV infection such as the gastrointestinal tract, which
      are at present refractory to treatment.

PMID- 9187922
TI  - Pathophysiology of HIV-associated diarrhea.
AB  - Considerable advances have been made in the evaluation and treatment of diarrhea
      in HIV-infected individuals, although gaps in knowledge still exist. The
      availability of newer and more powerful antiretroviral agents should allow a
      better definition of the effect of local HIV infection on intestinal function.
      Further attention to the pathophysiology of diarrhea should lead to improvements
      in diagnosis and treatment.

PMID- 9187923
TI  - Gastrointestinal pathology in HIV-infected patients.
AB  - Specific pathologic processes, particularly oral, esophageal, and intestinal
      infections, are common in the alimentary tract of AIDS patients. Many of these
      diseases are adequately assessed only by biopsy with histologic examination. Most
      are rare or unreported in immunocompetent hosts and are easily missed by those
      not familiar with them. This article describes the gross or endoscopic and
      histologic appearances and the diagnostic criteria for enteric pathologic
      processes seen in HIV-infected individuals.

PMID- 9187924
TI  - Oral and esophageal disorders.
AB  - This article focused on the approach to oral and esophageal disorders in patients
      with AIDS. Most of these disorders respond to various therapeutic regimens. Some
      of the oral complications can be prevented with dental prophylaxis, whereas
      recurrent esophageal disease in some patients may require long-term suppressive
      therapy. As patients with AIDS live longer with lower CD4 counts,
      gastroenterologists need to become familiar with the approach to and management
      of the more common lesions of the mouth and esophagus.

PMID- 9187925
TI  - Diarrheal diseases associated with HIV infection.
AB  - Diarrhea is a major complication of HIV infection and adversely impacts health
      care costs, quality of life, and even survival of patients. There is a wide
      variety of potential causes of diarrhea in HIV-infected patients, and the number
      of pathogens found continues to increase with time. In addition, there is some
      controversy concerning the role of some organisms in the pathogenesis of diarrhea
      and the appropriate diagnostic evaluation of affected patients. This article
      reviews our current understanding of these pathogens and some of the diagnostic
      and therapeutic approaches for diarrhea associated with HIV infection.

PMID- 9187926
TI  - Diagnosis and treatment of hepatic disease in patients with HIV.
AB  - Liver involvement with opportunistic infections and neoplasms is a well
      recognized component of AIDS, affecting most patients. The cause of hepatic
      disease in these patients may be divided into hepatitis, granulomatous disease,
      mass lesions, vascular lesions, hepatotoxic drugs, and nonspecific findings. With
      a rational approach, most patients with AIDS and liver disease can be diagnosed
      and treated in a cost-effective manner with low morbidity.

PMID- 9187927
TI  - Gallbladder and biliary tract disease in AIDS.
AB  - Biliary disease occurs in a subset of AIDS patients with CD4 counts of less than
      100 per mm3. These patients present with right upper quadrant and epigastric
      pain, cholestasis, and usually abnormal findings on imaging. In 75% of patients,
      an associated opportunistic infection can be identified. In patients with biliary
      disease, pain is often relieved following endoscopic sphincterotomy, whereas
      cholecystectomy provides pain relief in patients with acalculous cholecystitis.

PMID- 9187928
TI  - The pancreas in AIDS.
AB  - Although autopsy studies reveal significant pancreatic lesions in about 10% of
      AIDS patients, pancreatic lesions infrequently produce symptoms and are rarely
      recognized premortem. Patients with AIDS can develop pancreatic disease from
      causes not related to AIDS or AIDS-specific lesions. AIDS-specific causes include
      opportunistic infection, AIDS-associated neoplasia, and medications used to treat
      complications of AIDS. Pancreatic involvement is usually part of a widely
      disseminated tumor and rarely produces clinical symptoms.

PMID- 9187929
TI  - Anorectal diseases.
AB  - A proper understanding of the disease of the anorectum in the HIV-positive
      population mandates a familiarity with the ongoing advances in antiviral
      chemotherapy, mechanisms of oncogenesis, and effect of HIV infection on wound
      dynamics. As the prognosis for HIV-infected patients improves, therapies must
      reflect the expected increased survival of these patients.

PMID- 9187930
TI  - Surgical risk assessment and management in patients with HIV disease.
AB  - Determining the perioperative risks associated with surgical procedures performed
      in patients with HIV disease is a difficult and complex task. Because HIV is a
      contagious, blood-borne pathogen, it threatens the health and well-being of both
      patient and health care provider. Despite poor early results, there is now
      convincing evidence that HIV infection is not a significant, independent risk
      factor for major surgical procedures. In practice, the authors evaluate the risk
      of surgery in patients with HIV infection using the same basic tools and
      guidelines applied to the uninfected, with the best predictors of surgical
      morbidity and mortality stemming from a careful and accurate assessment of the
      patient's cardiopulmonary, renal, endocrine, and nutritional reserve. Although
      HIV disease provides a unique constellation of diagnoses and challenges to the
      health care provider, the risk of major surgery in this population is not unlike
      that for other immunocompromised or malnourished patients. The authors believe
      that members of the surgical team have a professional, moral, and ethical
      responsibility to provide the highest possible quality of care for their
      patients, regardless of their HIV status. If after weighing the risks and
      benefits to the patient the surgeon believes the procedure will have a positive
      effect on the patient's life, the surgeon must offer surgical treatment. To do
      less does a disservice to the patient, the provider, and the profession as a
      whole.

PMID- 9187931
TI  - Malnutrition in HIV infection.
AB  - Malnutrition is a common complication of HIV infection and plays a significant
      and independent role in morbidity and mortality. Many studies have been conducted
      to assess the appropriate role of nutrition in the clinical management of HIV
      infection. The complex nature of AIDS wasting, however, requires individualized
      strategies when providing nutritional support. Algorithms to assist in the
      diagnosis and treatment of malnutrition in HIV infection serve as general
      guidelines.

PMID- 9187932
TI  - Molecular diagnosis of gastrointestinal infections associated with HIV infection.
AB  - Developments in medical microbiology in the past 20 years have had a profound
      impact on our understanding of infectious diseases and have led the way in the
      development of new diagnostic techniques. Molecular diagnostic techniques are
      generally more sensitive, specific, and rapid than conventional methods by which
      infectious agents are detected. For many of the opportunistic infectious agents
      of the gastrointestinal tract found in HIV-infected individuals, the application
      of molecular diagnostic techniques to the clinical laboratory is in its infancy.
      In this article, methods by which these techniques can be evaluated are
      demonstrated, and the current status and potential future application of these
      techniques for each gastrointestinal opportunistic pathogen are described.

PMID- 9187933
TI  - Apolipoprotein E genotyping and cerebrospinal fluid tau protein: implications for
      the clinical diagnosis of Alzheimer's disease.
AB  - Apolipoprotein E (ApoE) genotyping was conducted in sporadic Alzheimer's disease
      (AD, n = 91) as well as in other dementing disorders including Parkinson's
      disease (PD, n = 73), autopsy-confirmed diffuse Lewy body disease (DLBD, n = 16),
      progressive supranuclear palsy (n = 13), vascular dementia (n = 55), alcoholic
      dementia (n =25) and normal control subjects (n = 77). ApoE epsilon 4 allele
      frequency was significantly higher in AD (33.5%, p < 0.001), DLBD (40.6%, p <
      0.001) and demented PD (29.4%, p < 0.05) compared to that in normal controls
      (11.7%). The association of the ApoE epsilon 4 allele with AD was more pronounced
      in early-onset AD (46.4%) than in late-onset AD (27.8%). 46% of the AD
      individuals developed AD without association to ApoE epsilon 4, and epsilon 4
      homozygotes were found not only in AD, but also in many of other dementing
      disorders. These results suggest that ApoE genotyping cannot provide certainty
      about the presence of absence of AD, and that it should be used as an adjunct to
      other diagnostic tests for AD. On the other hand, cerebrospinal fluid (CSF) tau
      levels were significantly elevated (p < 0.0001) in AD (78.0 +/- 44.2 pg/ml)
      compared to those in normal controls (10.6 +/- 8.6 pg/ml). The specificity and
      the sensitivity of distinguishing AD from normal controls was 95.0 and 91.2%,
      respectively. Elevated CSF-tau levels were also detected in some patients with
      acute neurological diseases including meningoencephalitis, Creutzfeld-Jacob
      disease, normal pressure hydrocephalus and vitamin B12 deficiency encephalopathy.
      Increased CSF-tau levels in AD were found regardless of the age at onset,
      clinical stage, ApoE genotype, alpha 1-antichymotrypsin genotype, and presenilin
      1 genotype. The CSF-tau levels continued to be abnormal during the progression of
      AD. These results suggest that CSF-tau serves as an unequivocal and reliable
      biological marker to aid in the clinical diagnosis of AD.

PMID- 9187934
TI  - Possible different mechanism between amyloid-beta (25-35)-and substance P-induced
      chemotaxis of murine microglia.
AB  - The mechanism of murine microglial chemotaxis induced by amyloid-beta protein (A
      beta (25-35)) was investigated. A beta (25-35) dose-dependently stimulated
      microglial chemotaxis at concentrations between 100 pM and 10 nM. Substance P, a
      NK-1 agonist, stimulated chemotaxis at concentrations of 10 nM or more. GR-64349,
      a NK-2 agonist, and senktide, a NK-3 agonist, did not stimulate microglial
      chemotaxis. We examined whether homologous desensitization of chemotaxis would
      occur by A beta (25-35). The chemotactic effect of microglia was homologously
      desensitized by 10 nM A beta (25-35). On the other hand, substance P at 10 nM did
      not desensitize the A beta (25-35)-induced chemotaxis. These data show that A
      beta (25-35) induces the chemotaxis of microglia probably through a receptor
      other than the NK-1 receptor.

PMID- 9187935
TI  - Interaction of aluminum with paired helical filament tau is involved in
      neurofibrillary pathology of Alzheimer's disease.
AB  - Since the first reports of aluminum-induced neurofibrillary degeneration in
      experimental animals, extensive studies have been performed to clarify the role
      played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional
      evidence implicating aluminum in AD includes elevated levels of aluminum in the
      AD brain, epidemiologic data linking aluminum exposure to AD, and interactions
      between aluminum and protein components in the pathologic lesions of AD, i.e.,
      neurofibrillary tangles (NFTs) and senile plaques. As most of this evidence is
      circumstantial and some of it is not consistent in all reports, the role of
      aluminum in the pathogenesis of AD has remained controversial. However, the
      interaction of aluminum with altered forms of tau in the paired helical filaments
      (PHFs) of neurofibrillary lesions is highly likely to contribute to the formation
      of NFTs because (1) aluminum and abnormally phosphorylated tau (known as PHF tau)
      are colocalized in NFTs, and (2) aluminum is known to preferentially interact
      with such phosphorylated proteins. Recently, it was demonstrated that aluminum
      binds selectively to PHF tau, induces PHF tau to aggregate, and retards the in
      vivo proteolysis of PHF tau. These data suggest that aluminum could serve as a
      cofactor in the formation of NFTs by interacting with PHF tau. This review
      summarizes the current understanding of how aluminum might contribute to the
      formation of neurofibrillary lesions from PHF tau in neurons of the AD brain.

PMID- 9187936
TI  - Effect of estrogen on isoforms of nitric oxide synthase: possible mechanism of
      anti-atherosclerotic effect of estrogen.
AB  - While estrogen is known to prevent the development of atherosclerosis, the
      mechanism is not completely understood. We investigated the effects of superoxide
      dismutase, acetylcholine, and other compounds on the release of nitric oxide (NO)
      by measuring the relaxation responses of aortic rings, with and without intact
      endothelium, taken from rabbits under various experimental conditions. The aorta
      of female rabbits released a greater amount of NO than did that of
      oophorectomized females and male rabbits. The greater basal release of NO in
      female rabbits was decreased in animals with atherosclerosis induced by a high
      cholesterol diet. We also investigated the effect of estrogen on endothelial,
      neuronal and inducible NO synthase (NOS), NOS-3, NOS-1 and NOS-2, respectively.
      Preincubation with a physiologic concentration of 17 beta-estradiol (10(-12) to
      10(-8) M) over 8 h significantly enhanced the activity of NOS-3 in the
      endothelial cells of cultured human umbilical vein and bovine aortas. 17 beta
      Estradiol also enhanced the release of NO from endothelial cells as measured by
      an NO selective meter and NO2-/N/3-, metabolites of NO. Western blot showed a
      similar effect of 17 beta-estradiol on NO. Estrogen increased NOS-3 via a
      receptor-mediated system. Low concentrations of 17 beta-estradiol (10(-10) to 10(
      8) M) enhanced the activity of crude NOS-1 in the cytosolic fraction of rabbit
      cerebella. Partially purified NOS-1, obtained from the cytosolic fraction by DEAE
      column chromatography, had a similar response to estrogen. Estrogen at a low dose
      enhanced the fluorescence of dansyl calmodulin and augmented it in high doses. We
      also investigated the effect of estrogen on NOS-2. When J774 cells, a murine
      macrophage cell line, were incubated with interferon-r and lipopolysaccharide,
      NOS-2 was induced and a large amount of NO was released. Pre- or co-incubation of
      17 beta-estradiol inhibited the induction of NOS-2 protein and NO release. The
      estrogen receptor antagonists, tamoxifen and ICI 182780, inhibited that effect of
      17 beta-estradiol. 17 beta-Estradiol inhibited the induction of NOS-2 by a
      receptor-mediated system. These results may offer a new mechanism for the anti
      atherosclerotic effect of 17 beta-estradiol.

PMID- 9187937
TI  - Possible participation of Fas-mediated apoptosis in the mechanism of
      atherosclerosis.
AB  - Apoptosis is a programmed cell death that plays a major role during development,
      homeostasis, and in many diseases. Recent evidence has demonstrated the death of
      vascular smooth muscle cells (VSMCs) within advanced human atheroma. In the rat
      balloon-injury model, apoptotic cells were specifically identified in the
      neointima. The presence of apoptotic cells was demonstrated by in situ terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). To clarify
      the mechanisms that trigger apoptosis in atherosclerotic lesions, we examined
      whether cytokines released from macrophages can modulate Fas, a death signal, in
      cultured human VSMCs. Simultaneous treatment with interleukin-1 (IL-1) and tumor
      necrosis factor-alpha (TNF-alpha) but not with each cytokine alone induced
      upregulation of Fas in VSMCs. However, coincubation with NG-monomethyl-L
      arginine, an inhibitor of nitric oxide (NO) synthesis, inhibited the upregulation
      of Fas induced by IL-1 and TNF-alpha. Incubation with sodium nitroprusside, a NO
      donor, also induced upregulation of Fas in VSMCs. Furthermore, fluorescent
      nuclear staining with Hoechst 33258 revealed that monoclonal antibody to human
      Fas significantly enhanced NO-induced apoptotis in VSMCs. These findings suggest
      that macrophage-derived cytokines can induce upregulation of Fas through a NO
      dependent mechanism in VSMCs. Thus, Fas-mediated apoptosis may regulate apoptotic
      death of VSMCs during atherogenesis.

PMID- 9187938
TI  - Increased blood plasminogen activator inhibitor-1 and intercellular adhesion
      molecule-1 as possible risk factors of atherosclerosis in Werner syndrome.
AB  - Werner syndrome is a rare premature aging syndrome accompanied by severe
      atherosclerosis. The etiology of atherosclerosis is suspected to be due to its
      complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But
      from an autopsy case we found that some other risk factors may be involved in the
      mechanism of atherosclerosis in this syndrome. Previously we revealed that the
      plasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin
      fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of
      tissue plasminogen activator and a possible risk factor of atherosclerosis. This
      led us to assess the plasma concentration of PAI-1. Our working hypothesis was
      that the PAI-1 gene was upregulated or not fully suppressed in cells responsible
      for the production of PAI-1 in plasma as well as in fibroblasts. The results show
      a high concentration of plasma PAI-1. One of the well-known physiological
      substances that induce the PAI-1 gene is tumor necrosis factor-alpha, which also
      induces other possible risk factors of atherosclerosis, intercellular adhesion
      molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum
      concentrations of ICAM-1 to be elevated in patients with this syndrome. We
      conclude that high concentrations of PAI-1 and ICAM-1 in blood may be one of the
      potent causes of severe atherosclerosis in Werner syndrome.

PMID- 9187939
TI  - The origin of genetic defects in the human and their detection in the
      preimplantation embryo.

PMID- 9187940
TI  - The gonadotrophin-releasing hormone receptor: structural determinants and
      regulatory control.

PMID- 9187941
TI  - Classification and comparison of oral contraceptives containing new generation
      progestogens.
AB  - New generation-oral contraceptives containing desogestrel or gestodene, and
      possibly also norgestimate, are more or less similar with respect to
      contraceptive efficacy, cycle control and acceptability. They also show a more
      favourable metabolic profile in comparison with older preparations. The
      desogestrel-containing preparations Gracial and Marvelon, and possibly also the
      gestodene-containing preparation Gynera, have demonstrated a good efficacy in
      well-controlled studies in the treatment of mild to moderate acne and/or
      hirsutism. There may be differences between new generation oral contraceptives
      with respect to their effects on metabolic variables like high-density
      lipoprotein cholesterol and sex hormone-binding globulin. These differences are
      most probably modulated by variations in both the pharmacokinetics and
      selectivity of the progestogenic components. Of particular relevance here may be
      the recent finding that approximately 20% of administered norgestimate is
      metabolized into levonorgestrel. For use in clinical practice, it is of
      considerable help to have different preparations containing a range of oestrogen
      doses with the same progestogen. They allow the clinician to 'tailor make' the
      choice of oral contraceptives for those starting pill use or those switching to
      another combination due to symptomatology or changed circumstances, e.g.
      advancing age, smoking, etc. In this respect, desogestrel-containing oral
      contraceptives allow the most flexible approach.

PMID- 9187942
TI  - Clinical applications of growth hormone for ovarian stimulation.
AB  - The realization of the existence of an intra-ovarian regulating mechanism
      involving insulin-like growth factor-I (IGF-I), a mediator of growth hormone (GH)
      action that augments the ovarian response to gonadotrophins, has prompted a
      number of clinical trials exploring the use of GH as an adjuvant for ovarian
      stimulation with human menopausal gonadotrophin. A critical review of these
      studies pinpoints a select group of infertile patients who may benefit from this
      co-treatment, particularly those who have a surgical, pathological or medically
      induced dysfunction of GH kinetics. The mechanism of this action, the effective
      dose needed and the implications regarding the interface of GH, IGF-I and ovarian
      physiology and pathology are now becoming clearer. A greater understanding of GH
      action on the ovary may in future benefit patients afflicted by anovulatory
      infertility and those requiring ovulation induction for in-vitro fertilization.

PMID- 9187943
TI  - Diagnosing testicular function using 31P magnetic resonance spectroscopy: a
      current review.
AB  - Patients with low sperm counts combined with normal concentrations of
      gonadotrophins, and in whom physical examination and post-ejaculatory urine
      analysis are normal, present a diagnostic dilemma. This situation can be caused
      by testicular failure or by ductal obstruction, which have very different
      clinical prognoses. Ductal obstruction might be correctable by microsurgical
      vasovaso/vasoepididymostomy, whereas this approach is of no use in primary
      testicular failure. A possible diagnostic step for these patients is a testicular
      biopsy to differentiate between hypospermatogenesis and a normal gonad. However,
      to date testicular biopsy is seldom performed because of its invasive character.
      An alternative accurate, non-invasive method to assess testicular function could
      be very helpful in the evaluation of idiopathic azoospermia or idiopathic
      oligozoospermia. During the past decade, magnetic resonance (MR) spectroscopy has
      been developed from a scientific tool into a non-invasive clinical diagnostic
      tool and has also been used to study testicular function. Recent studies have
      shown that 31P-MR spectroscopy, based upon differences in the ratio of peaks of
      phosphomonoester to beta-adenosinetriphosphate, is a non-invasive technique able
      to differentiate between groups of patients with testicular failure and ductal
      obstruction, and it correlates reasonably well with the averaged mean Johnsen
      score of testicular biopsy. The role for a non-invasive technique in the
      diagnosis of male infertility, such as 31P-MR spectroscopy, can be manifold. It
      serves not only as an alternative for biopsy but can also be used to assess
      obstruction as the cause of infertility in patients with subnormal sperm counts,
      and to predict the chances of pregnancy in patients planned for vasovasostomy to
      correct a prior vasectomy. However, the main limitation to MR spectroscopy
      becoming a universal clinical diagnostic technique is the limited availability of
      1.5 Tesla MR scanners.

PMID- 9187944
TI  - Ovarian stimulation and ovarian tumours: a critical reappraisal.
AB  - Increased interest has arisen recently about the possible association between
      ovarian stimulation and ovarian tumours. In this article, the current knowledge
      on the epidemiology, pathogenesis and aetiology of ovarian tumours is extensively
      reviewed in relation to the existing literature on the relationship between
      ovulation induction and ovarian neoplasia. The available data from
      epidemiological studies and case reports do not support a direct causal
      relationship between ovarian stimulation and ovarian cancer. However, it is
      possible that ovarian stimulants may have an augmenting role for special
      categories of tumours, e.g. sex-cord stromal tumours. A definite answer to this
      important issue may be reached through large prospective epidemiological studies
      or large retrospective well-designed case-control studies.

PMID- 9187945
TI  - Hospital-acquired infections in the United States. The importance of
      interhospital comparisons.
AB  - To use infection rates as a basis for measuring quality of care, the rates must
      be meaningful for interhospital comparison. A crude, overall nosocomial infection
      rate of a hospital provides no means of adjustment for patients' intrinsic or
      extrinsic risks. Before interhospital comparison, rates should be adjusted for
      nosocomial infection risk factors. Interhospital comparison of rates requires
      that a hospital participate in a multicenter surveillance system or aggregated
      national database. This article outlines a series of questions for hospital
      administrations to pose before entering such an endeavor.

PMID- 9187946
TI  - Role of molecular epidemiology in infection control.
AB  - Molecular typing methods have enabled infection control personnel to investigate
      outbreaks and endemic nosocomial infections more quickly and thoroughly than they
      could have with basic epidemiologic and microbiologic methods. This article
      reviews molecular typing methods that have been used successfully in the practice
      of hospital epidemiology. Included is an explanation of the basic principles of
      these methods and a description of their strengths and weaknesses.

PMID- 9187947
TI  - Infection control in ambulatory care.
AB  - This article provides a structured review of the English literature focusing on
      areas that theoretically pose the greatest risk for nosocomial infections in
      ambulatory care. The review describes variations in methods of surveillance and a
      general paucity of studies that provide reliable estimates of the risk for
      infections in the ambulatory environment.

PMID- 9187948
TI  - Control of antimicrobial resistance in the health care system.
AB  - Resistance continues to spread in nosocomial pathogens in acute care hospitals
      and other key settings of managed health care systems. Appropriate control
      measures for such resistant organisms depend, in part, on the pathways by which
      resistance has arisen. Unfortunately, these pathways differ greatly from organism
      to organism and setting to setting. Although the epidemiology of resistant
      organisms sometimes is similar to that of susceptible organisms of the same kind,
      in some situations it may be quite different. This article highlights some of the
      pathways leading to the development of resistance in bacteria and the relevance
      of these mechanisms to measures for the control of resistant bacteria in hospital
      and community settings.

PMID- 9187949
TI  - Frontiers of occupational health. New vaccines, new prophylactic regimens, and
      management of the HIV-infected worker.
AB  - New prophylactic or treatment options are available for a number of infectious
      diseases that may be transmitted in the health care setting. Infectious diseases
      that can now be prevented by vaccination of the employee include hepatitis A,
      pertussis, hepatitis B, and primary varicella. New prophylactic or treatment
      regimens are available for Neisseria meningitidis, Streptococcus pyogenes, and
      Bordetella pertussis; treatment of multidrug-resistant tuberculosis is also
      discussed. Finally, management of the HIV-infected health care worker is
      reviewed.

PMID- 9187950
TI  - Bloodborne pathogen transmission in health care workers. Risks and prevention
      strategies.
AB  - Occupational transmission of hepatitis B virus (HBV), hepatitis C virus, and HIV
      has been documented. The risk for occupationally transmitted infection varies for
      these three viruses. Despite effective pre- and postexposure prophylaxis for HBV
      and recent recommendations for postexposure chemoprophylaxis after an HIV
      exposure, the best approach to prevent occupational bloodborne infection is the
      prevention of blood exposures. Epidemiologic data of percutaneous injuries and
      other blood contacts have provided the basis for prevention strategies. These
      strategies include the development of improved engineering controls, work
      practices, and personal protective equipment.

PMID- 9187951
TI  - Infection control challenges in child-care centers.
AB  - The child-care environment predisposes young children to infection with a variety
      of pathogens. Factors contributing to increased incidence of certain infections
      include age-specific hygiene behaviors, immunologic immaturity of young children,
      and exposure to pathogens with high infectivity. Respiratory tract and enteric
      pathogens are responsible for most illnesses, but a number of other agents are
      also important. Hygienic interventions, especially handwashing, remain important
      in infection control, but maintenance of appropriate immunization levels plays a
      crucial role in disease prevention in the child-care setting. Future
      interventions will center on development of new vaccines to eliminate
      susceptibility of young children to as many infectious agents as possible and
      continued evaluation of other preventive measures.

PMID- 9187952
TI  - Vancomycin-resistant enterococcus. Detection, epidemiology, and control measures.
AB  - VRE have spread rapidly since their initial description in 1988. Although much
      has been learned about the epidemiology of VRE, further studies are needed to
      establish the reservoirs of the organism and the relative importance of various
      modes of transmission. There is considerable anecdotal evidence that nosocomial
      transmission of VRE can be thwarted by using measures such as those recommended
      by HICPAC, especially if they are implemented promptly after VRE have been
      introduced into hospitals.

PMID- 9187953
TI  - Prevention of nosocomial transmission of Mycobacterium tuberculosis.
AB  - The recent resurgence of TB together with the ongoing HIV epidemic has resulted
      in a larger number of infectious TB patients being admitted to US health care
      facilities. These patients have become a source for both nosocomial (patient-to
      patient) and occupational (patient-to-health care worker) M. tuberculosis
      transmission. Infectious MDR-TB patients serve as even greater potential
      infectious sources because they often remain AFB smear and culture positive for
      months to years. The keys to the prevention of nosocomial and occupational
      transmission of M. tuberculosis is conducting a risk assessment for each area of
      the facility and instituting appropriate control measures, having a high index of
      suspicion by clinicians for infectious TB in those who present with consistent
      signs and symptoms, rapid triage of such patients to isolation areas and their
      appropriate clinical work-up, and the institution of effective antituberculous
      therapy. Infection control personnel should ensure that infectious TB patients
      are isolated in appropriate isolation rooms (i.e., negative pressure, greater
      than or equal to 6 ACH, and direct external exhaust of the room air). Health care
      workers with infectious TB patient contact should be instructed in the
      epidemiology of M. tuberculosis transmission, the role of respirators in
      protecting the health care worker from airborne inoculation, and the importance
      of periodic health care worker TST. The nosocomial TB outbreaks in the 1980s and
      1990s document that M. tuberculosis can be transmitted to both patients and
      health care workers in US health care facilities when appropriate infection
      control measures are not fully implemented. Follow-up studies at some of these
      institutions, however, document that when infection control measures similar to
      the 1990 or 1994 CDC TB Guidelines are fully implemented, M. tuberculosis
      transmission to both patients and health care workers can be reduced or
      eliminated. Protection of both patients and health care workers from M.
      tuberculosis infection is dependent on an understanding and full implementation
      of the 1994 CDC TB Guidelines.

PMID- 9187954
TI  - Nosocomial Candida. Epidemiology, transmission, and prevention.
AB  - The NNIS and the newly established SCOPE data indicate that the relative
      proportion of organisms causing nosocomial bloodstream infections has changed
      over the last decade, with Candida species now being firmly established as one of
      the most frequent agents. The epidemiology of nosocomial candidemia is
      continually being refined, but established predisposing factors including
      immunosuppression and malignancies, use of broad spectrum antibiotics, and use of
      indwelling central catheters remain as significant risk factors. The high cost of
      health care and greater attention to continuous quality improvement will
      stimulate better and more effective ways of diagnosing and treating candida
      infections using combined clinical and microbiologic acumen. There is room for
      optimism as newer antifungal agents with reduced toxicities have impact on
      therapy of candidal infections. Aggressive development of still more agents and
      reformulations of older agents continue in earnest. Even greater consolation
      comes from the increased awareness of lay and medical personnel alike regarding
      the appropriate and judicious use of antimicrobial agents.

PMID- 9187955
TI  - Nosocomial pneumonia. Diagnosis and prevention.
AB  - Ventilator-associated pneumonia (VAP) is an important complication in patients
      with respiratory failure who undergo endotracheal intubation and mechanical
      ventilation. VAP cannot be accurately diagnosed by clinical or radiographic
      criteria or culture of endotracheal aspirates; however, it can be accurately
      diagnosed by histopathologic examination of lung tissue, rapid cavitation of a
      pulmonary infiltrate, culture of empyema fluid, percutaneous lung needle
      aspiration, simultaneous recovery of the same microorganism from cultures of
      respiratory secretions, and blood and quantitative culture of lower respiratory
      tract secretions obtained by bronchoscopy. VAP can be prevented by proper
      decontamination and use of ventilatory support equipment, practice of proper
      nursing techniques during care of the mechanically ventilated patient, and use of
      face mask ventilation in selected patients.

PMID- 9187956
TI  - Prevention of infections in bone marrow transplant recipients.
AB  - Bone marrow transplantation (BMT) is increasingly used in the treatment of
      hematologic malignancies, solid tumors, and congenital diseases. The number of
      patients receiving a BMT increased from approximately 5000 in 1989 to 12,000 in
      1995. Infectious complications are the most common cause of morbidity and
      mortality in the peritransplant period in patients undergoing autologous BMT.
      Additionally, infectious complications are a serious cause of complications in
      recipients of matched sibling allogeneic BMT, unrelated BMT, and related
      mismatched BMT.

PMID- 9187957
TI  - Magnitude and prevention of nosocomial infections in the intensive care unit.
AB  - Nosocomial infections among intensive care unit (ICU) patients usually are
      related to the use of invasive devices (e.g., mechanical ventilators, urinary
      catheters, or central venous catheters). This article discusses the impact of
      these devices and other risk factors for nosocomial infection in ICU patients.
      Data on etiologic pathogens and device-related infection rates from the National
      Nosocomial Infection Surveillance System are presented, general infection control
      guidelines for ICUs are reviewed, and special infection control problems
      encountered in ICUs are discussed.

PMID- 9187958
TI  - Differentiation of respiratory epithelium: the effects of retinoic acid and
      carcinogens on the expression of mucociliary vs. squamous phenotype.
AB  - Changes in ultrastructural characteristics and mucin gene expression were
      examined in rat tracheal explants cultured in a synthetic medium +/- retinoic
      acid (RA), benzo[a]pyrene (B[a]P) and N-methyl-N-nitrosourea (NMNU). In the RA(+)
      cultures, no changes in either ultrastructural features or mucin gene expression
      were detected after 48 h incubation. After 96 h incubation, however, the
      ultrastructural features associated with the squamous phenotype were
      characteristics of cultures containing the two carcinogens and the mucin gene
      expression was slightly reduced. Thus, in the presence of retinoic acid, the
      carcinogen induced changes in cytology to the squamous phenotypes were not
      matched by a marked loss of mucin gene expression. Explants cultured for 48 h
      without RA and +/- carcinogens showed none of the cytological changes associated
      with onset of the squamous phenotype. While mucin mRNA was still detected, it was
      clearly reduced compared to 48 h cultures in RA(+) medium. However, 48 h later,
      all explants exhibited pronounced squamous metaplasia and the mucin message
      decreased to trace levels. Thus, the results of these experiments with B[a]P and
      NMNU in RA(+) and RA(-) media indicates that at least the early carcinogen
      induced changes may be distinct from those associated with the retinoid pathway
      controlling expression of the mucin component of the mucociliary epithelium.

PMID- 9187960
TI  - Macrophage-mediated candidacidal activity is augmented by exposure to eosinophil
      peroxidase: a paradigm for eosinophil-macrophage interaction.
AB  - Various disease states are associated with eosinophilia and the release of
      eosinophil peroxidase (EPO) into the microenvironment. The present study targets
      the effects of low levels of EPO on macrophage (M phi) phagocytosis and
      intracellular killing of Candida albicans as well as M phi oxidative activity
      measured as the luminescence product of luminol dioxygenation. Resident murine
      peritoneal M phi were exposed to various concentrations of EPO. Chemiluminescence
      data indicate that nanomolar concentrations of EPO markedly enhanced the
      dioxygenation activity (respiratory burst) of M phi. In other studies, the
      exposure of M phi to 0.17 microM EPO for 10 min. enhanced M phi-mediated
      candidacidal activity 10 fold. The above data indicate that EPO enhances certain
      M phi functions. Also the results illustrate a previously un-recognized
      interaction between eosinophils and M phi and implicate yet another possible role
      for EPO in host defenses against disease.

PMID- 9187959
TI  - Platelet-activating factor stimulates interleukin-6 production by human
      endothelial cells and synergizes with tumor necrosis factor for enhanced
      production of granulocyte-macrophage colony stimulating factor.
AB  - The interaction between human endothelial cells (EC) and leukocytes during
      inflammation is in part mediated through the release of soluble factors. Since
      platelet-activating factor (PAF) is a potent mediator of inflammatory responses,
      we investigated the potential of PAF to modulate IL-6 and GM-CSF production by
      EC. Exposure of these cells to PAF resulted in a concentration-dependent increase
      in IL-6 production, with a maximum at 10(-10) M PAF. Sequential incubation of EC
      with PAF and TNF alpha resulted in a synergistic increase of IL-6 production.
      This effect was specific for PAF since it was prevented by preincubation with the
      PAF receptor antagonist, WEB 2086. Northern blot analysis revealed enhanced IL-6
      mRNA expression in PAF-treated EC. However, the synergy observed in protein
      synthesis between PAF and TNF alpha was not reflected in IL-6 mRNA accumulation,
      suggesting a post-translational modulation. Pretreatment of EC with the protein
      synthesis inhibitor cycloheximide before their exposure to PAF resulted, after
      washout of the cycloheximide, in a markedly augmented production of IL-6,
      suggesting a synergy between augmented IL-6 mRNA accumulation by PAF and IL-6
      mRNA superinduction by cycloheximide. GM-CSF production by EC was also stimulated
      by the combined effects of PAF and TNF alpha, but PAF alone did not affect GM-CSF
      production. Taken together, our data suggest that PAF can stimulate EC to
      synthesize cytokines, including IL-6 and GM-CSF, which may contribute to local
      and, possibly, systemic responses during inflammation.

PMID- 9187961
TI  - Ischemia/reperfusion injury in the rat colon.
AB  - This study investigated metabolic and biochemical consequences of colonic
      ischemia/reperfusion (I/R) in the rat and evaluated whether antioxidants prevent
      I/R-induced functional damage in the rat colon. The surgical preparation involved
      a 10 cm segment of the colon and occlusion of the superior mesenteric artery
      (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the
      superior mesenteric vein (SMV) was collected to measure blood gases, lactic acid
      (LA) and arachidonic acid (AA) metabolites. Tissue xanthine oxidase (XO) and
      thiobarbituric acid (TBA) derivatives were measured before and after reperfusion.
      In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a
      water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TBA
      was measured. After ischemia, the colon displayed a metabolic shift from aerobic
      to anaerobic course by increasing lactic acid production in the colon (183%
      increase in SMV lactate level compared 87% in the SMA; p < 0.03). After 10
      minutes of reperfusion, circulating 6-keto-prostaglandin F1 alpha increased by
      3.85 fold (p < 0.001) and thromboxane B2 increased by 2 to 3 fold. An Ischemia
      time longer than 60 minutes was required to cause changes in tissue XO levels.
      Tissue TBA levels showed a good dose response corresponding with I/R time. I/R
      (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and
      mucosal permeability, respectively. MDL 73404 and 5-aminosalicylic acid
      significantly inhibited the vascular permeability and decreased LA, AA, XO and
      TBA. These observations provide the first direct experimental evidence for I/R
      induced damage in the colon and some of its effects can be reversed by
      conventional and novel antioxidants.

PMID- 9187962
TI  - Studies of skin-window exudate human neutrophils: increased resistance to
      pentoxifylline of the respiratory burst in primed cells.
AB  - Human neutrophils were isolated both from peripheral blood (PB) and from aseptic
      inflammatory exudates obtained by the Senn's skin window technique (SW). The
      respiratory burst (O2- production) induced by in response to n-formyl-methionyl
      lencyl-phenylalanine (fMLP) and by serum-treated zymosan (STZ) was investigated
      using a microplate assay. SW neutrophils were primed to enhanced fMLP-dependent
      O2- production in response to fMLP but not to STZ. Pentoxifylline, a cAMP
      elevating drug, dose-dependently inhibited the respiratory burst in any
      experimental condition, but the dose-effect curves were markedly different
      according the stimulant used and the source of the cells. With fMLP as stimulant,
      a significant inhibition of the O2- production by PB neutrophils was obtained
      using doses of 10 micrograms/ml, while SW neutrophils were inhibited only by
      doses equal or higher than 100 micrograms/ml. With STZ as stimulant, the
      inhibition of the respiratory burst of PB neutrophils and of SW neutrophils was
      obtained only with doses higher than 400 micrograms/ml and 1 mg/ml respectively.
      Pentoxifylline dose-dependently (10 micrograms/ml to 1 mg/ml) increased the
      intracellular adenosine 3'-5'-cyclic monophosphate (cAMP) to the same extent in
      SW and in PB neutrophils. These data indicate that the priming of neutrophil
      oxidative metabolism by in vivo inflammation is associated with an increase in
      the resistance to the regulating effect of cAMP on the fMLP-dependent activation
      pathway of NADPH oxidase. The fact that therapeutic doses of pentoxifylline do
      not inhibit the respiratory burst of primed neutrophils may have relevance in the
      interpretation of the clinical effects of this drug.

PMID- 9187963
TI  - Altered arachidonic acid metabolism in urate crystal induced inflammation.
AB  - Gout is an acute rheumatic disorder that occurs in connection with the deposition
      of monosodium urate (MSU) crystals in the joints. This disease is characterized
      by intermittent episodes of severe pain and inflammatory joint swelling which are
      seemingly driven by prostaglandins. In this study we investigated the effect of
      MSU crystals on arachidonic acid (AA) metabolism in the mouse. We have
      demonstrated that prostaglandins and other AA metabolites were transiently formed
      after MSU crystal injection with peak levels occurring after 10 min. In contrast,
      free AA levels remained high for 2-4 hours after MSU crystal injection. By
      contrast, when exogenous AA was administered instead of MSU crystals, both the
      eicosanoids and AA diminished at the same high rates. The metabolism of
      exogenously administered AA to eicosanoids was inhibited by pretreatment with MSU
      crystals. No inhibition of AA metabolism was observed when mice were pretreated
      with AA itself, Ca2+ ionophore (A23187), or zymosan. We conclude that the MSU
      crystal treatment of mice results in a transient eicosanoid production which is
      followed by attenuated AA metabolism. It could be that MSU crystals similarly
      inhibit AA metabolism in gout and thereby limit the duration of gout attacks.

PMID- 9187964
TI  - Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.
AB  - Leukocyte adhesion to vascular endothelial cells is an essential step in the
      development of inflammatory diseases. We have searched for inhibitors of
      leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs
      and found that bruceine B (0.2 microgram/ml; 0.44 microM) inhibited human
      neutrophil or T cell adhesion to tumor necrosis factor-alpha (TNF) stimulated
      human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil
      adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic
      effects, as determined by measurement of the level of lactate dehydrogenase (LDH)
      activity in conditioned medium. The effect of bruceine B on neutrophil adhesion
      to HUVEC was not seen when the neutrophils were preincubated with bruceine B.
      However, inhibitory effects were evident when the HUVEC were preincubated with
      bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide
      stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings
      suggest that bruceine B may have anti-inflammatory activity.

PMID- 9187965
TI  - Differential effects of cell density on 5-lipoxygenase (5-LO), five-lipoxygenase
      activating protein (FLAP) and interleukin-1 beta (IL-1 beta) expression in human
      neutrophils.
AB  - We have analyzed the effect of cellular density of 5-Lipoxygenase (5-LO), 5
      lipoxygenase-activating protein (FLAP) and interleukin-1 beta (IL-1 beta) gene
      expression in neutrophils from healthy subjects under culture conditions of low
      and high cell density. By using RT-PCR techniques, we have found that 5-LO mRNA
      accumulation decreased in cells cultured at high density, while FLAP mRNA is not
      affected. De novo 5-LO synthesis, as well as steady-state levels, were reduced in
      cells maintained at high density. In contrast, the high density conditions lead
      to the induction of IL-1 beta gene at the RNA and protein levels as measured by
      RT-PCR and by immunoprecipitation. These results suggest that cellular density
      plays a role in gene modulation when neutrophils are accumulating at an
      inflammatory site since neutrophils obtained from the synovial fluid of patients
      with RA exhibit a protein synthesis profile similar to that observed in
      peripheral blood neutrophils cultured at high density.

PMID- 9187967
TI  - Supplementation of vitamin E may attenuate skeletal muscle immobilization
      atrophy.
AB  - The aim of this study was to investigate whether oxidative stress contributes to
      the development of atrophy in immobilized muscles, and, under this assumption,
      whether the administration of an antioxidant has beneficial effects to attenuate
      immobilization atrophy. One hindlimb of rats was immobilized for eight days, the
      contralateral leg served as control. One experimental group was supplemented with
      vitamin E. In the soleus muscle, the glutathione content as an indicator for
      oxidative stress was measured, and muscle fiber diameters were evaluated to
      estimate muscle atrophy. The biochemical results indicate no pronounced oxidative
      stress in the immobilized muscles and even less oxidative stress in the vitamin E
      supplemented muscles (with and without immobilization). Eight days of
      immobilization lead to a 35% atrophy, while with vitamin E the muscles atrophied
      only by 12%. This difference can be attributed to the action of vitamin E as a
      scavenger for free radicals and, on the other hand, to an atrophy promoting
      effect of oxidative stress. Oxidative stress is hypothesized to exist during the
      initial phase, but to disappear after some days of immobilization. It is
      suggested that oxidative stress plays a role in initiating muscle atrophy, and
      supplementation of vitamin E prior to and during the early phase of
      immobilization is recommended. Moreover, such may also be useful during
      remobilization to avoid additional oxidative stress with rehabilitative exercise.

PMID- 9187966
TI  - Chemotactic factors released in culture by intact developing and healing skin
      lesions produced in rabbits by the irritant sulfur mustard.
AB  - Development, peak and healing lesions were induced in the skin of rabbits by
      topical applications (on different days) of the chemical irritant sulfur mustard
      (SM). Immediately after the rabbits were euthanized, the intact lesions were
      excised and organ-cultured for 17 to 20 hours. The culture fluids from early,
      peak and healing SM lesions all showed high chemotactic activity for both PMN and
      MN. This finding suggests that the PMN and MN, seen microscopically in tissue
      sections of the lesions, were entering continuously, even during the healing
      process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8,
      and proteases producing the complement fragment C5a. Other studies from our
      laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO
      mRNAs was increased in SM lesions. Chemotactic activity was released by both live
      and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts,
      suggesting that these cells were major sources of the chemotaxins produced by the
      SM lesion explants. Explants of normal skin produced considerable chemotactic
      activity for MN, but not for PMN. Chemotactic activity for PMN, and the release
      of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants
      infiltrated by leukocytes.

PMID- 9187968
TI  - Influence of time of day on the anxiolytic effects of exercise.
AB  - The purpose of this investigation was to study state anxiety responses associated
      with running at different times of day. Thirty volunteers (15 Female and 15 Male)
      who regularly exercised in the morning (n = 10), at noon (n = 10), or in the
      evening (n = 10) completed three running sessions at 0600 h-0800 h, 1100 h-1300
      h, and 1600 h- 1800 h. A post-hoc analysis was also performed comparing
      individuals who ran at their preferred time (N = 18) with individuals who ran at
      a time different from their preferred time (N = 11). The duration and pace of
      these runs were based upon each runner's "preferred exertion", and this was held
      constant across trials for each participant. The estimated metabolic cost did not
      differ across the three sessions, but there was a significant difference between
      Female (mean = 11.4 METS) and Male (mean = 12.9 METS) runners. The dependent
      variables were state anxiety, perceived exertion, heart rate, tympanic
      temperature and blood pressure. Data were analyzed by means of repeated measures
      MANOVA for multifactor experiments. State anxiety was reduced significantly (p <
      0.05) for both the women and men, and this effect was independent of time of day.
      Furthermore, this effect occurred regardless of whether or not the individual's
      usual exercise time was the preferred time. Perceived exertion increased
      significantly (p < 0.05) from half-way through to the end of the run and this
      response occurred regardless of time of day. None of the remaining variables were
      influenced by time of day. It is concluded that the anxiolytic effects of running
      exercise are independent of the time of day the exercise is performed.

PMID- 9187969
TI  - Inspiratory muscle fatigue following running to volitional fatigue: the influence
      of baseline strength.
AB  - Respiratory muscle fatigue has been demonstrated following short-term exercise to
      volitional fatigue, as well as following prolonged submaximal exercise. There is
      some suggestion that the respiratory muscles of 'athletic' individuals have
      superior strength and greater fatigue resistance but it is not known whether
      inspiratory muscle strength influences fatigueability of the inspiratory muscles.
      The present study examined this question in 24 moderately trained young men.
      Inspiratory muscle strength was measured at residual volume using a hand held
      Mouth Pressure Meter before and after an incremental, multistage shuttle run to
      volitional fatigue. Following the run, there was a significant fall in
      inspiratory mouth pressures (-10.5 +/- SD 8.2%; p < 0.001 Pre- vs Post Pipeak).
      The subjects with the weakest inspiratory muscles exhibited significantly greater
      fatigue than those with the strongest (-17.0 +/- SD 7.8% c.f. 6.8 +/- SD 4.4% for
      the 25th and 75th percentiles respectively p < 0.01). These data support existing
      evidence that the respiratory muscles fatigue following high intensity exercise.
      In addition, they provide new evidence that this phenomenon occurs in moderately
      trained young men and that the severity of the fatigue is related to the baseline
      strength of the inspiratory muscles.

PMID- 9187970
TI  - Effect of fluid ingestion on orthostatic responses following acute exercise.
AB  - Orthostatic tolerance is impaired following an acute bout of exercise. This study
      examined the effect of fluid ingestion following treadmill exercise in restoring
      the cardiovascular responses to an orthostatic stress. Five men (age, 29.6 +/-
      3.4 yrs) were exposed to a graded lower body negative (LBNP) pressure protocol (0
      to -50 mmHg) during euhydration without exercise (C), 20 minutes after exercise
      dehydration (D), 20 minutes after exercise and fluid ingestion (FI20), and 60
      minutes after exercise and fluid ingestion (FI60). Fluid ingestion (mean +/- SE)
      consisted of water-ingestion equivalent to 50% of the body weight lost during
      exercise (520 +/- 15 ml). Exercise dehydration resulted in significantly higher
      heart rates (119 +/- 8 vs 82 +/- 7 bpm), lower systolic blood pressures (95 +/-
      1.7 vs 108 +/- 2.3 mmHg), a smaller increase in leg circumference (3.7 +/- 4 vs
      6.9 +/- 1.0 mm), and an attenuated increase in total peripheral resistance (2.58
      +/- 1.2 vs 4.28 +/- 0.9 mmHg/L/min) at -50 mmHg LBNP compared to the C condition.
      Fluid ingestion (both 20 and 60), partially restored the heart rate, systolic
      blood pressure, and total peripheral resistance responses to LBNP, but did not
      influence the change in leg circumference during LBNP (4 +/- 0.3 for R20 and 2.8
      +/- 0.4 mm for R60). These data illustrate the effectiveness of fluid ingestion
      on improving orthostatic responses following exercise, and suggest that
      dehydration is a contributing factor to orthostatic intolerance following
      exercise.

PMID- 9187971
TI  - After-effects of a high altitude expedition on blood.
AB  - The aim of the study was to investigate blood alterations caused by altitude
      acclimatization which last more than few days after return and might play a role
      for exercise performance at sea level. Measurements were performed in 12
      mountaineers before, during and either 7/8 or 11/12 days after a Himalaya
      expedition (26-29 days at 4900 to 7600 m altitude). [Erythropoietin] rose only
      temporarily at altitude (max. +11 +/- 1 [SE] mu/ml serum). After return
      hemoglobin mass (initially 881 +/- 44 g, CO-Hb method) was increased by 14% (p <
      0.01); aspartate aminotransferase activity in erythrocytes (initially 682 +/- 25
      U/l) was augmented (day 7: +964 +/- 152 U/l, day 11: +533 +/- 107 U/l) indicating
      reduced mean cell age. Calculated blood volume (+14%) was influenced by red cell
      formation at altitude but also by plasma expansion at sea level. The half
      saturation pressure for Hb-O2 (pH 7.4, 37 degrees C) as well as the 2.3
      diphosphoglycerate concentration were already initially high (32.1 +/- 0.5 mmHg,
      20.5 +/- 0.7 mumol/g Hb) and showed only a nonsignificant tendency to increase
      after return. Also Hill's n was consistently high in the mountaineers, whereas
      the Bohr coefficients were slightly increased only after descent. Probably the
      preparatory physical training, partly in the Alps, and the stay in the Himalaya
      influenced O2-affinity for a prolonged time. The adaptations might reduce the
      loss of physical performance capacity at altitude and be part of altitude
      training effects.

PMID- 9187972
TI  - No evidence of oxidative stress after a triathlon race in highly trained
      competitors.
AB  - Long distance triathlons, due to the large amounts of oxygen uptake they cause,
      may lead to the generation of reactive oxygen species, and consequently to
      oxidative stress and damage. We sought to verify this hypothesis. Twelve of the
      18 male triathletes who participated in the study took part in a long distance
      triathlon, the others did not. The prerace blood samples were drawn 48 h before
      the race and repeatedly until the fourth day of recovery. The myoglobin
      concentrations increased immediately after the race. The concentrations of
      methemoglobin, disulfide glutathione (GSSG), and thiobarbituric reactive
      substances did not significantly change after the race. Although the race induced
      an inflammatory response, evidenced by the variations in neopterin concentrations
      and leukocyte counts, there was no consecutive oxidative stress. The basal GSH
      values were correlated significantly with cycling training volume (r = 0.55) and
      VO2max (r = 0.53). Muscle damage can occur without evidence of oxidative stress
      or oxidative damage. We conclude that the magnitude of the antioxidant defense
      system enhancement depends on training loads. Because of their training status,
      the triathletes did not suffer from oxidative damage after they finished the long
      distance triathlon race.

PMID- 9187974
TI  - The effects of mountain bike suspension systems on energy expenditure, physical
      exertion, and time trial performance during mountain bicycling.
AB  - The purpose of this 3-Phase study was to investigate the effects of suspension
      systems on muscular stress, energy expenditure, and time trial performance during
      mountain biking. Three suspension systems were tested, a rigid frame bike (RIG),
      a suspension fork bike (FS), and a front and rear suspension bike (FSR). Phase I
      and II consisted of cycling at 16.1 km.hr-1 over a flat, bumpy course for 63 min.
      Phase III consisted of ascending (ATT), descending (DTT), and cross country (XTT)
      time trials. Phase I assessed muscular stress by 24 h change in CK, Phase II
      assessed HR, VO2, VE, and Phase III assessed performance responses to the
      suspension systems. The 24 hr change in CK was greater for RIG than FS and FSR
      (+91.9 +/- 79.5 IU vs +8.6 +/- 17.5 IU and +9.7 +/- 21.8 IU). Mean HR was greater
      for RIG than FS and FSR (153.7 +/- 15.6 bpm vs 146.7 +/- 15.4 bpm, 146.3 +/- 16.2
      bpm). Subjects rode significantly faster on FS than FSR and RIG during the XTT
      (30.9 +/- 2.0 min vs 32.3 +/- 3.6 min, 32.3 +/- 3.2 min). Subjects RPE was lower
      for FSR than FS and RIG, however, no differences were observed for VO2, VE, ATT,
      or DTT. Cyclists incurred less muscular stress, indicated by CK and HR, when
      riding the FS and FSR. Although the FS and FSR weigh from 0.7 to 2.2 kg more than
      RIG, no differences were observed for energy expenditure and that riding the FS
      in a XTT resulted in a faster finishing time than FSR or RIG.

PMID- 9187973
TI  - Hormonal responses to excessive training: influence of cross training.
AB  - The purpose of this investigation was to examine the changes in blood hormone
      levels elicited by increases in training volume. After 30 d of recording their
      training volume and intensity (normal training, 57.5 +/- 10.9 km.wk-1), 11 well
      trained distance runners completed two randomly assigned 10 day periods of
      increased training volume (200% normal training). Each increased training regimen
      was preceded by two weeks of reduced training (80% normal training). The
      increased training regimens consisted of either running only (RT) at 200% of
      normal training distance or running (100% normal training) and cycling (kcal =
      100% normal training: CT). During each increased training regimen the subjects
      ran 10 consecutive afternoons at a distance equivalent to 100% of normal training
      (approximately 75% VO2max) and performed eight additional morning sessions (0500
      0800 h). During RT the subjects performed their morning workouts on a treadmill
      and during CT the workouts were performed on a bicycle ergometer. Blood samples
      were obtained (0500-0700 h) after 15 min supine rest after normal training, and
      before (day 0), on day five (day 5) and following ten days (day 11) of RT and CT.
      Serum was analyzed for testosterone, free testosterone, cortisol,
      adrenocorticotropic hormone, luteinizing hormone, and dehydroepiandrosterone
      sulfate. Free testosterone was significantly (p < 0.05) reduced on day 5 and day
      11 of RT and CT compared to day 0 and total testosterone was lower on day 5 than
      day 0. However, no significant treatment or interaction effects were observed for
      total testosterone or free testosterone. Dehydroepiandrosterone sulfate was also
      significantly lower across time, i.e., day 11 was lower than day 0 and day 5;
      however, cortisol, adrenocorticotropic hormone, and luteinizing hormone were not
      significantly altered during RT or CT. The endocrine responses to an increased
      training volume with cross training and mode specific training were similar.

PMID- 9187975
TI  - Validity of peak oxygen uptake calculations from heart rate deflection points.
AB  - Two graded exercise tests on a cycle ergometer were examined in regard to their
      predictability of the peak oxygen uptake (VO2peak) based upon the deflection
      points (Dp) in the heart rate curves. The "constant duration" test (DUR-test) was
      based upon data from a previous maximal test. The "constant distance" test (DIS
      test) was based upon the subjects' body weight and fitness level. In both tests
      29 male subjects, 25 to 35 years, pedalled until exhaustion and from these tests
      the Dp variables (heart rate, DpHR, and the workload, DpW) and the VO2peak were
      determined. The subjects also underwent the Astrand & Ryhming-test (A&R-test).
      Deflection points could be detected for 15 subjects (52%) in the DUR-test and for
      18 subjects (62%) in the DIS-test. In 13 subjects a Dp in both tests could be
      determined with a test-retest correlation coefficient of r = 0.66 for the DpHR
      and r = 0.79 for the DpW. Multiple regression analysis yielded the following
      equations: VO2peak = 7.7538 + 0.0199 DpW-0.0506 DpHR (n = 15; r = 0.87; SEE =
      0.291.min-1) for the DUR-test and VO2peak = 5.8673 + 0.0200 DpW -0.0354 DpHR (n =
      18; r = 0.88; SEE = 0.401.min-1) for the DIS-test. Compared to the measured
      VO2peak of the DUR-test and the DIS-test, the calculated VO2peak from the A&R
      test has a correlation coefficient of r = 0.74 and r = 0.77 with a SEE of 0.57
      (13.3%) and 0.55 (12.7%) l.min-1, it was concluded that, when a deflection point
      in the W-HR curve is found, the VO2peak can be calculated more accurately with
      the developed regression equations in this study than with the A&R-test. However,
      since the graded exercise cycle tests presented in this paper are only reliable
      in 33 of the 58 cases, they are useless for evaluating the VO2peak in a practicle
      sense, especially when no previous information about the appearance of a Dp is
      available.

PMID- 9187976
TI  - Cellular and humoral immune response to exercise among gymnasts and untrained
      girls.
AB  - Recent studies reported reduced immunity in athletes following exercise. Physical
      activity affects both cellular and humoral immune functions. Scant information
      exists on exercise-induced changes in the immune system among children. The
      purpose of the present study was to investigate the effect of aerobic exercise on
      several aspects of cellular and humoral functions among 10-12 year-old highly
      trained female gymnasts (n = 7) and untrained girls (n = 6). All girls were pre
      pubertal. Venous blood samples were drawn before, immediately after and 24 h
      following 20 min of treadmill running (heart rate 170-180 beats.min-1). White
      blood cells' number rose significantly following exercise and remained elevated
      for 24 h. The increase in leukocyte number was due to an increase in granulocytes
      as well as an increase in lymphocytes and monocytes. While neutrophil count
      returned to basal values after 24 h, lymphocytes and monocytes number remained
      elevated 24 h following exercise. Exercise resulted in a significant elevation of
      T cell lymphocytes, T helpers, T suppressors and natural killer cells. All values
      returned to normal after 24 h. There were no changes in B cell lymphocytes
      following exercise. Exercise had no effect on serum IgA, IgM, IgE, IgG and sub
      types of IgG (IgG1, IgG2, IgG3 and IgG4). No differences were observed between
      gymnasts and untrained girls. In summary, the exercise-induced changes in
      cellular and humoral immune functions among the girls were generally similar to
      those described in adults. Whether the transitory effects of exercise on the
      immune system are related to increased susceptibility to illness is still
      questionable.

PMID- 9187977
TI  - Brief report: healed myocarditis as a cause of ventricular repolarization
      abnormalities in athlete's heart.
AB  - In the past myocarditis has been suggested as a possible cause of repolarization
      abnormalities in sportsmen, but, to our knowledge, no direct in-vivo
      demonstration of this relationship has so far been found. We report the cases of
      three professional athletes with repolarization changes at rest and/or during
      exercise and mild segmental wall motion anomalies in the left ventricle on
      echocardiography, in whom myocarditis was diagnosed by non-invasive and invasive
      clinical investigations, including endomyocardial biopsy. We think that probably
      the frequency with which myocarditis is responsible for electrocardiographic and
      echocardiographic abnormalities in athletes has so far been underestimated, and
      that caution must be employed when interpreting minor segmental wall motion
      abnormalities on resting and exercise echocardiograms in trained subjects as
      being due to athlete's hart, especially when they present with repolarization
      changes.

PMID- 9187978
TI  - An epidemiological analysis of the injury pattern in indoor and in beach
      volleyball.
AB  - This study was designed to evaluate the injuries in indoor and in beach
      volleyball, and to compare the injury pattern in the two different types of
      volleyball. Injuries in 295 volleyball players were recorded during the beach
      volleyball season 1993 and during the following indoor volleyball season 1993 to
      1994. The method of enquiry was two identical questionnaires. Equal numbers of
      men and women, elite and recreational players were represented. In beach
      volleyball 24 injuries were reported and 286 in indoor volleyball, representing
      an incidence of 4.9 injuries per 1000 volleyball hours in beach volleyball and
      4.2 in indoor volleyball. The most frequent injuries were acute injuries located
      in the ankle and finger and overuse injuries in the knee and shoulder. The injury
      pattern was different in indoor and in beach volleyball. In beach volleyball most
      injuries occurred in field defence and in spiking, with overuse injuries in the
      shoulder as the major site. In indoor volleyball most injuries occurred during
      blocking and spiking, resulting most frequently in acute finger and ankle
      injuries, respectively.

PMID- 9187979
TI  - Ankle bracing in running: the effect of a Push type medium ankle brace upon
      movements of the foot and ankle during the stance phase.
AB  - Functional ankle braces are designed to limit medio-lateral movements of the
      ankle without affecting ankle dorsiflexion or plantar flexion. As running forms a
      basic activity in sports, the current study investigated the influence of wearing
      a Push type medium ankle brace upon movements of the foot and ankle during the
      stance phase in running. The movements of the lower extremity of seven trained
      male long-distance runners were filmed frontally (250 s-1) and sagittally (50 s
      1) while running at 4.5 +/- 0.1 m.s-1 over a Kistler force platform. The tested
      brace significantly reduced the range (total subtalar eversion 13.3 deg vs 18.1
      deg, p < 0.05) and rate of subtalar eversion (maximal velocity -309 deg.s-1 vs 
      533 deg.s-1). Plantar and dorsiflexion were not affected. The vertical impact
      force peak was not altered. It was argued that, although this might not be the
      prime design feature of the tested ankle brace, this orthotic offers a strategy
      to influence the range and the rate of subtalar eversion. It may have the
      potential to prevent runners from overuse injuries associated with overpronation,
      but interaction between the passive support by the brace and the muscular
      stabilization of the ankle joint needs further investigation.

PMID- 9187980
TI  - Use of the stages of change in exercise adherence model among older adults with a
      cardiac diagnosis.
AB  - PURPOSE: Researchers have recommended use of the Stages of Change in Exercise
      Adherence (STAGES), a process-oriented model, to better understand exercise
      adherence behavior. This study aimed to further understand the process by
      evaluating the predictors of exercise adherence and the validity of the STAGES
      model among older adults (N = 349) with a cardiac diagnosis after discharge from
      a cardiac rehabilitation inpatient program. METHODS: Recently discharged
      inpatient participants, aged 65 years or older and ambulatory, responded to a
      computer-assisted telephone interview regarding their exercise behaviors and
      attitudes toward exercise (mean response time = 32.3 minutes). Between 55 and 80
      participants in each of five stages of exercise adherence were interviewed.
      Demographic profiles and other information were obtained from a chart review of
      cardiac rehabilitation inpatient records. RESULTS: Perceived self-efficacy,
      perceived benefits of exercise, interpersonal support for exercise, and perceived
      barriers to exercise were significant predictors of exercise adherence using
      direct entry discriminant analysis. These predictors accounted for 50% of the
      variance in stage of exercise adherence. The theoretical ordering of the STAGES
      model was supported (P < .0001). Exercise time significantly increased with each
      subsequent stage of exercise adherence from the precontemplation stage to the
      maintenance stage. CONCLUSIONS: This study evaluated the validity of the STAGES
      model in a sample of older cardiac rehabilitation participants. The STAGES model
      can be applied to the study of exercise behavior among this group of older
      adults.

PMID- 9187981
TI  - The effect of a home-based, case-managed, multifactorial risk-reduction program
      on reducing psychological distress in patients with cardiovascular disease.
AB  - BACKGROUND: This study examined the effects of a nurse-case-managed,
      multifactorial, risk-reduction program on psychological distress among patients
      after myocardial infarction (MI). METHODS: Five hundred eighty-five men and women
      aged 70 years or younger, who were hospitalized for acute MI in one of five San
      Francisco Bay Area hospitals, were randomized to receive a nurse-managed, home
      based, multifactorial risk-reduction program (n = 293) or usual care (n = 292).
      The program, which began in the hospital, included a brief screen for five areas
      of psychological distress with further evaluation if indicated, monitoring during
      the follow-up phone calls, and referral for mental health treatment if needed.
      Patients were assessed with single-item scales at baseline, and at 6 and 12
      months. Separate analyses were performed for patients with moderate-to-severe
      levels on the psychological distress domains and for those with low levels.
      RESULTS: There was a significant reduction in the psychological distress
      variables for all patient groups between baseline and 12 months. The program had
      a significant effect on reducing anxiety in the patient group with low levels of
      anxiety and reducing anger in the patient group with frequent episodes of anger
      but, overall, the treatment and control groups showed equal levels of
      improvement. CONCLUSION: Among patients post-MI without complications,
      psychological distress decreases significantly during the 12 months after MI.

PMID- 9187982
TI  - Self-reported depression in patients with coronary heart disease.
AB  - BACKGROUND: Assessing depression in cardiac patients is challenging because
      somatic symptoms of depression may be the result of physical illness. This study
      examined self-reported symptoms of depression in patients with cardiovascular
      disease. METHOD: Three hundred six patients with cardiovascular disease completed
      the Inventory to Diagnose Depression (IDD), which is a self-report depression
      scale. RESULTS: Practically all patients reported some symptoms on the IDD, but
      only a small number had scores in the range suggestive of depression. Somatic
      symptoms did not contribute disproportionately to depression scores but affective
      and cognitive symptoms were stronger indicators of depression in these patients.
      Factor analysis identified one factor that represented a general syndrome of
      depression. CONCLUSIONS: The results suggest that the IDD has promise as a
      measure to screen for depression in cardiac patients.

PMID- 9187983
TI  - Arm training reduces the VO2 and VE cost of unsupported arm exercise and
      elevation in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) may
      develop dyspnea with minimal arm activity, thoracoabdominal dyssynchrony with
      unsupported arm exercise (UAEX) and increased oxygen uptake (VO2), and minute
      ventilation (VE) with simple unsupported arm elevation (UAE) and UAEX. We
      investigated whether unsupported arm training, as the only form of exercise,
      could decrease the VO2 and VE cost (percentage increase from resting baseline)
      associated with unsupported arm elevation and exercise, respectively. METHODS:
      Twenty-six patients with severe COPD were randomized to 21-24 sessions of
      unsupported arm (ARMT) or low-intensity resistive breathing (RBT) training as the
      only form of exercise. Patients were studied before and after training using a
      metabolic cart and esophageal and gastric pressures to evaluate metabolic and
      respiratory muscle function. RESULTS: After ARMT, the VO2 (58% vs 38% increase, P
      < 0.05) and VE (41% v. 21% increase, P < 0.05) cost for UAEX at exercise isotime
      decreased and endurance time increased. Similarly the VO2 (25% vs 18% increase, P
      < 0.05) cost decreased and VE no longer increased in response to 2 minutes of UAE
      after ARMT. The RBT group showed no such change. No improvement in ventilatory
      load or respiratory muscle function could be identified to explain the
      physiologic changes observed. After ARMT, mean inspiratory flow (VT/TL), a
      measure of central respiratory drive, was reduced during UAEX and the expected
      increase during UAE did not occur. CONCLUSION: We conclude that arm training
      reduces the VO2 and VE cost of UAE and UAEX, possibly through improved
      synchronization and coordination of accessory muscle action during unsupported
      arm activity.

PMID- 9187984
TI  - Outcome assessment in cardiac rehabilitation. Health-related quality of life and
      economic evaluation.

PMID- 9187985
TI  - Glucose: enough versus too much.

PMID- 9187986
TI  - Glucose versus lactated Ringer's solution during pediatric cardiac surgery.
AB  - OBJECTIVE: Whether intraoperative fluid infusion should contain glucose during
      pediatric cardiac surgery remains controversial. This study was performed to
      compare the effects of glucose and glucose-free solutions on blood glucose and
      blood insulin levels during total repair of congenital heart diseases. DESIGN:
      Prospective randomized and blinded study. SETTING: Cardiovascular university
      center. PARTICIPANTS: Forty nondiabetic children, weight ranging from 4 to 10 kg,
      scheduled for cardiac surgical procedures requiring cardiopulmonary bypass (CPB)
      without total circulatory arrest. INTERVENTIONS: Group R (n = 20) was
      administered lactated Ringer's solution intraoperatively, and group G (n = 20)
      received 5% glucose. Fluids were infused at a rate of 3 mL/kg/h in the two groups
      from the induction of anesthesia to the end of the surgical procedure. Blood
      glucose and insulin were sampled before infusion (Tzero), before CPB (T1), 10
      minutes after initiation of CPB (T2), 10 minutes after initiation of rewarming
      (T2), and at the end of the procedures (T4). Postoperatively, blood glucose was
      measured at the first, 12th, and 24th hours. MEASUREMENTS AND RESULTS: During the
      prabypass period, three children in group R had severe hypoglycemia (blood
      glucose < 40 mg/dL). After initiation of CPB, blood glucose increased in both
      groups, with a small difference at the end of the procedure. No infants in the
      two groups had blood glucose higher than 239 mg/dL. CONCLUSIONS: Glucose
      withdrawal during pediatric cardiac surgery induces threatening hypoglycemia
      during the prabypass period, and moderate intraoperative glucose administration
      (2.5 mg/kg/min) is not responsible for major hyperglycemia.

PMID- 9187987
TI  - Effect of pump flow rate on cerebral blood flow during hypothermic
      cardiopulmonary bypass in adults.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of cardiopulmonary
      bypass flow rate on cerebral blood flow and cerebral metabolic rate for oxygen
      during hypothermic (27 degrees C) cardiopulmonary bypass. DESIGN, SETTING, AND
      PARTICIPANTS: The investigation was a prospective, randomized study in a tertiary
      care hospital setting. The 30 participants were volunteer adult cardiac surgical
      patients at a single institution. INTERVENTIONS: The N2O saturation method of
      Kety and Schmidt was used to determine global cerebral blood flow and metabolic
      rate during four periods: prebypass, cardiopulmonary bypass (CPB) (27 degrees C)
      flow rates of 2.3 and 1.2 L/min/m2, and 30 minutes post-CPB. Anesthesia consisted
      of fentanyl and midazolam; pH management was alpha-stat, and mean arterial
      pressure was maintained at 50 to 70 mmHg throughout CPB. MEASUREMENTS AND MAIN
      RESULTS: In the context of an unchanged mean arterial pressure, the pump flow did
      not affect cerebral blood flow or metabolic rate during hypothermic CPB. Systemic
      venous oxygen saturation was also maintained during reduced flow at 27 degrees C.
      Hemodilution during hypothermic CPB maintained cerebral blood flow at prebypass
      levels. In the postbypass period, persistent hemodilution resulted in an elevated
      cerebral blood flow. CONCLUSIONS: Brain oxygenation is well maintained at lower
      than conventional pump flow levels during CPB. There may be practical advantages
      to reduced flows during hypothermia, and flow reductions do not appear to
      adversely affect cerebral blood flow or metabolism.

PMID- 9187988
TI  - The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow
      in dogs.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of pulsatility
      on cerebral blood flow, cerebral metabolism, and renal blood flow over a range of
      cardiopulmonary bypass temperature and flow conditions. DESIGN/SETTING: The
      investigation was prospective, randomized, and performed in a canine physiology
      laboratory at the Mayo Foundation. PARTICIPANTS AND INTERVENTIONS: Anesthetized
      dogs were studied during pulsatile (n = 9) or nonpulsatile (n = 10)
      cardiopulmonary bypass at two flow rates (2.4 and 1.2 L/min/m2) at each of three
      temperatures (37 degrees, 32 degrees, and 27 degrees C). Pulsatility was achieved
      by use of a pediatric intraaortic balloon pump. Cerebral blood flow and metabolic
      rate were determined using the sagittal sinus outflow method. Renal blood flow
      was determined by a periarterial ultrasonic flow probe. MEASUREMENTS AND MAIN
      RESULTS: In the pulsatile group, a pulse pressure of 29 mmHg had no effect on
      cerebral blood flow or metabolism at any temperature under either flow condition.
      Renal blood flow was also unaffected by pulsatility, but decreased with
      hypothermia and reduced pump flow. Pulsatility also did not attenuate the
      systemic effects of normothermic hypoperfusion. CONCLUSIONS: Pulsatility has no
      significant effect on cerebral or renal perfusion over a broad range of
      cardiopulmonary bypass temperature and flow conditions. Cerebral blood flow and
      metabolism were functions of temperature but not pulsatility or flow rate. Renal
      blood flow was affected by both temperature and cardiopulmonary bypass flow rate
      but not by pulsatility. Finally, central nervous system perfusion may be
      preserved under low-flow cardiopulmonary bypass conditions by shunting of
      perfusion from splanchnic vascular beds.

PMID- 9187989
TI  - Comparison of pulsatile versus nonpulsatile perfusion on the postcardiopulmonary
      bypass aortic-radial artery pressure gradient.
AB  - OBJECTIVE: To investigate whether the type of perfusion, pulsatile (PP) or
      nonpulsatile (NP), has any effect on the pressure gradient that exists between
      the aortic root and the radial artery after cardiopulmonary bypass (CPB). DESIGN:
      Prospective, randomized study. SETTING: Tertiary care, university hospital.
      PARTICIPANTS: Eighty patients undergoing elective, hypothermic coronary artery
      bypass graft (CABG) surgery. INTERVENTIONS: Pulsatile perfusion with a pulse
      pressure of 10 to 20 mmHg and a frequency of 60 to 80 beats/min was created
      during the hypothermic phase of CPB. Both the radial artery and aorta were
      cannulated and attached to separate transducers but displayed and analyzed on the
      same monitor. MEASUREMENTS AND MAIN RESULTS: Simultaneous recordings of radial
      artery and aortic root blood pressure were made prebypass, during CPB, and after
      discontinuation of CPB at 2, 5, and 10 minutes. During CPB, the PP group had a
      significantly higher mean pulse pressure measured at the aortic root than the NP
      group (15.5 +/- 8.1 v 1.7 +/- 2.7, p < 0.0001). The aortic-to-radial-artery
      gradient within both groups was significantly different after CPB for systolic
      (SBP), diastolic (DBP), and mean pressure (MAP) (p < 0.0001). There were,
      however, no statistically significant differences between the PP and NP groups in
      the aortic-to-radial-artery gradient after CPB for either SBP, DBP, or MAP.
      CONCLUSIONS: Pulsatile perfusion had no effect on the aortic root radial artery
      blood pressure gradient after CPB in elective CABG surgery patients.

PMID- 9187990
TI  - Evaluation of the accuracy and response time of STAT-mode continuous cardiac
      output.
AB  - OBJECTIVES: This study was conducted to compare continuous cardiac output (CCO)
      with bolus thermodilution cardiac output (BTD) at steady state, and to compare
      the response time of STAT CCO with that of trend CCO, mean arterial pressure, and
      mixed venous oxygen saturation [SvO2] during an acute hemodynamic change. DESIGN:
      Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty-nine
      patients undergoing cardiac surgery or liver transplantation. INTERVENTIONS: STAT
      and trend CCO were compared with BTD cardiac output during steady state
      intraoperatively and postoperatively in the intensive care unit. Ten patients,
      who required epicardial pacing after cardiac surgery, were studied to compare the
      response time of STAT CCO with that of trend CCO, mean arterial pressure, and
      BvO2 after a 10% to 20% increase in pacing rate. MEASUREMENTS AND MAIN RESULTS: A
      total of 108 cardiac output data sets were analyzed at steady state. Steady state
      was defined as stable heart rate and mean arterial pressure (+/- 5%) and stable
      central venous pressure (+/- 2 mmHg) measured immediately before and after each
      data set. Cardiac output ranged from 2.3 to 8.5 L/min. The correlation between
      STAT CCO and BTD was r = 0.94, and for trend CCO and BTD was r = 0.94. The bies
      and precision for STAT CCO versus BTD were 0.06 L/min (Cl 95%: -0.08 to 0.18) and
      0.61 L/min. The bias and precision for trend CCO versus BTD were 0.06 L/min (Cl
      95%: -0.04 to 0.16) and 0.49 L/min. Eleven data sets were analyzed to study
      response time of STAT CCO, which was defined as the first time the percent change
      of the mean of each variable was significantly increased from baseline.
      Significant increases in mean arterial pressure and SvO2 were detected after 30
      seconds (2.5%, p = 0.01) and 90 seconds (2.0%, p = 0.04), respectively. A
      significant increase in STAT CCO was reached at 270 seconds (4.4%, p = 0.005).
      Trend CCO tended to increase but did not reach statistical significance within 6
      minutes. CONCLUSIONS: STAT and trend CCO are accurate and precise and show close
      agreement with BTD cardiac output at steady state. The faster algorithm of STAT
      CCO offers some advantage over trend CCO during an acute hemodynamic change.
      However, because of the averaging process for determining CCO, the response time
      of STAT CCO is slower than that of mean arterial pressure and SvO2.

PMID- 9187991
TI  - Thermodilution cardiac output measurement during simultaneous volume infusion
      through the venous infusion port of the pulmonary artery catheter.
AB  - OBJECTIVE: To determine the effect on thermodilution cardiac output (TDCO)
      measurements of continuous volume infusion through the right atrial venous
      infusion port of the pulmonary artery catheter. DESIGN: Prospective, blinded,
      randomly allocated crossover. SETTING: Surgical intensive care unit in a
      university hospital. PARTICIPANTS: Forty-nine hemodynamically stable patients
      between the ages of 43 and 84 in the intensive care unit and with a pulmonary
      artery catheter in place. INTERVENTIONS: Each patient received two room
      temperature infusions (250 or 500 mL/hr) of 5% dextrose. Consecutive TDCO
      measurements were taken during each infusion and during a control period (no
      infusion). The sequence of infusion rates and control period was randomly
      determined. At both infusion rates, most patients exhibited a decrease in TDCO
      measurement of between 0.1 and 3.0 L/min. Although some patients exhibited an
      increase in measured TDCO, this increase was primarily between 0.1 and 0.5 L/min.
      MEASUREMENTS AND MAIN RESULTS: The mean TDCO measurements at infusion rates of 0,
      250, and 500 mL/hr were 6.77, 6.49, and 6.47 L/min, respectively. Measured TDCO
      decreased on volume infusion by 0.3 +/- 0.13 L/min (mean +/- SD, p < 0.02).
      CONCLUSION: Rapid continuous infusion of fluid through the venous infusion port
      of the pulmonary artery catheter significantly limits the accuracy of
      simultaneous TDCO measurements. Optimally, TDCO measurements should be avoided
      during rapid volume infusion.

PMID- 9187992
TI  - Continuous intraoperative noninvasive cardiac output monitoring using a new
      thoracic bioimpedance device.
AB  - OBJECTIVES: To compare a new noninvasive bioimpedance device with the standard
      thermodilution method during the intraoperative period in high-risk patients
      undergoing oncological surgery. DESIGN: Prospectively collected data with
      retrospective analysis. SETTING: The study was undertaken at a university
      hospital, single institution. PARTICIPANTS: Twenty-three selected adults
      undergoing extensive, ablative oncological surgery. INTERVENTIONS: Simultaneous
      measurements of cardiac output by a new bioimpedance method and the standard
      thermodilution method during the intraoperative and immediate postoperative
      periods. MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between the
      two methods was r = 0.89, p < 0.001. Bias and precision analysis between the two
      techniques showed a mean bias of 0.1 L/min and SD of the bias [precision] of 1.0
      L/min [95% level of agreement +2.1 L/min to -1.9 L/min]. After software
      enhancement, data from the last 11 monitored patients showed improved correlation
      between the two methods; r = 0.93, mean bias -0.1 L/min, and precision 0.8 L/min.
      Electrical and motion-induced interference only transiently impaired the
      performance of the new impedance method. CONCLUSION: This new impedance device is
      a safe, reliable, clinically acceptable alternative to the invasive
      thermodilution method in the operating room environment.

PMID- 9187993
TI  - Caval occlusion alters the shape of the ischemic and nonischemic pressure-length
      loop.
AB  - OBJECTIVES: The effects of changes in preload on paradoxical myocardial wall
      motion during ischemia have been previously studied. However, the studies have
      been performed using slow volume changes. It was decided to study the effects of
      fast changes in preload, which would occur during caval occlusion, on the
      regional pressure-length loops during ischemia. DESIGN: Retrospective trial.
      SETTING: Experimental animal laboratory in a university medical center.
      PARTICIPANTS: Ten anesthetized adult dogs. INTERVENTIONS: In an open chest
      preparation, regional ischemia was achieved by occluding the left anterior
      descending coronary artery for 10 minutes, with sudden caval occlusions being
      performed to assess the influence of preload on wall motion. MEASUREMENTS AND
      MAIN RESULTS: Left ventricular pressure and regional segmental lengths were
      measured. During caval occlusion, beat by beat, percent postsystolic shortening
      and percent systolic bulging in the ischemic region, percent isovolumetric
      shortening in the nonischemic region, and percent systolic shortening in both
      regions were calculated. Caval occlusion significantly decreased the end
      diastolic pressure (12.62 +/- 1.02 to 3.39 +/- 0.59 mmHg) and length. In the
      ischemic area, although systolic shortening became more negative (-1.8 +/- 0.79%
      to -9.65 +/- 1.08%), postsystolic shortening (9.66 +/- 0.73% to 15.53 +/- 1.2%)
      and systolic bulging (4.6 +/- 0.49% to 12.67 +/- 1.04%) increased. In the
      nonischemic area, systolic shortening decreased slightly but significantly (18.01
      +/- 3.24% to 14.93 +/- 3.64%) as isovolumetric shortening increased (2.77 +/-
      0.68 to 7.37 +/- 1.29%). Caval occlusion increased the rightward shift and
      accentuated the distortion of the ischemic loop. The nonischemic loop displayed a
      leftward shift of the systolic isovolumetric component and a slight decrease in
      percent total length change. CONCLUSION: Caval occlusion modifies the shape of
      the pressure-length loop of the ischemic myocardium. This change in shape may
      interfere with the assessment of regional systolic indexes obtained by caval
      occlusion in ischemic hearts.

PMID- 9187994
TI  - Cardiopulmonary effects of enoximone or dobutamine and nitroglycerin on mitral
      valve regurgitation and pulmonary venous hypertension.
AB  - OBJECTIVE: To compare the cardiovascular and pulmonary effects of the
      phosphodiesterase III inhibitor enoximone (EN) or a combination of dobutamine
      (DOB) and nitroglycerin (NTG) before and after mitral valve repair or
      replacement. DESIGN: Prospective, randomized, controlled clinical study. SETTING:
      University hospital. PARTICIPANTS: Twenty patients with mitral regurgitation and
      pulmonary venous hypertension scheduled for elective mitral valve surgery.
      INTERVENTIONS: Patients fulfilling the inclusion criteria of the study were
      randomly allocated into a group treated with EN (group 1, n = 10) or DOB and NTG
      (group 2, n = 10). A cardiopulmonary status was obtained after induction of
      anesthesia and mechanical ventilation during stable hemodynamic conditions
      (control). Then the patients received either EN (bolus dose 1.0 mg/kg followed by
      a continuous infusion of 10 micrograms/kg/min) or DOB (8.0 micrograms/kg/min) and
      NTG (1.0 microgram/kg/min) according to the randomization. After a period of 20
      minutes, all parameters were measured again. The study drugs were stopped, and
      cardiac surgery was performed. Infusions of EN (without additional loading dose)
      or DOB and NTG were started again in the above-described doses 10 minutes before
      separation from cardiopulmonary bypass (CPB). Respiratory and hemodynamic
      measurements were made 20 minutes after weaning from CPB and 60 minutes after
      admission of the patient to the intensive care unit. MEASUREMENTS AND MAIN
      RESULTS: Both groups were comparable regarding preoperative and control data.
      Before mitral valve surgery, cardiac output (CO) and heart rate (HR) increased by
      46% (p < 0.05) and 31% (p < 0.01) during infusion of EN with minor changes of
      mean systemic arterial pressure (PSA) and gas exchange. Mean pulmonary arterial
      pressure (PPA) decreased from 32 +/- 11 mmHg to 23 +/- 11 mmHg (p < 0.05).
      Similar alterations were observed in group 2 (delta CO + 26%, p < 0.05, delta HR
      + 39%, p < 0.01); however, PPA and calculated pulmonary vascular resistance
      remained unchanged. After separation from CPB, EN and DOB-NTG achieved comparable
      effects on CO, HR, and PSA, but PPA was significantly lower in group 1. In
      addition, venous admixture and alveolo-arterial oxygen tension gradient were
      lower in EN-treated patients. CONCLUSION: Enoximone or DOB and NTG have
      comparable effects on CO, PSA, and HR in mitral regurgitation and pulmonary
      hypertension, but EN is more effective in reducing PPA without deterioration of
      gas exchange.

PMID- 9187995
TI  - Acetylcholine reactivity in the pulmonary artery during cardiac surgery in
      patients with ischemic or valvular heart disease.
AB  - OBJECTIVE: During cardiopulmonary bypass, there is almost no blood flow through
      the pulmonary artery. Ischemia and reperfusion are known to attenuate the
      reaction to acetylcholine. An attenuated reactivity to acetylcholine in the
      pulmonary circulation after cardiopulmonary bypass was previously shown in
      children. The current study in adult patients was designed to analyze the change
      over time of acetylcholine reactivity after cardiac surgery. DESIGN: A
      prospective study. SETTING: The operating room and intensive care unit of a
      university hospital. PARTICIPANTS: Eighteen patients with ischemic or valvular
      heart disease. INTERVENTIONS: Pulmonary vascular resistance was measured with a
      pulmonary artery catheter before and during an infusion of acetylcholine. This
      procedure was done after induction of anesthesia before surgery and 1, 4, 8, and
      20 to 24 hours after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS:
      Pulmonary vascular resistance index decreased during infusion of acetylcholine
      before surgery by 27% from 286 +/- 27 dyne/sec/cm-5/m2 (mean and standard error
      of mean) to 209 +/- 28 and at 8 and 20 to 24 hours by 23% and 34%, respectively,
      288 +/- 27 to 221 +/- 29 and 229 +/- 22 to 150 +/- 17 (p < 0.001, paired t-test).
      One and 4 hours after cardiopulmonary bypass, no significant decrease was
      observed. CONCLUSIONS: These results confirm the finding of altered reactivity to
      acetylcholine in the pulmonary circulation after cardiopulmonary bypass. In view
      of the often prolonged tendency toward pulmonary hypertension observed in
      children, the recovery at 8 hours after surgery was unexpectedly rapid. The
      attenuated response to acetylcholine is most likely explained by relative
      ischemia in the pulmonary circulation during cardiopulmonary bypass.

PMID- 9187997
TI  - Early extubation after mitral valve surgery: a target-controlled infusion of
      propofol and low-dose sufentanil.
AB  - OBJECTIVE: In the current study, the use of a target-controlled infusion of low
      dose propofol was combined with a continuous infusion of sufentanil for patients
      undergoing mitral valve surgery. The purpose of the study was to evaluate the
      hemodynamic stability, the time to awakening and spontaneous ventilation, and the
      feasibility in an early extubation setting of a total intravenous anesthetic
      technique. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS:
      Fifteen patients scheduled for elective mitral valve surgery. INTERVENTIONS:
      Induction of anesthesia consisted of sufentanil (1 microgram/kg), propofol (1
      microgram/mL) target plasma concentration achieved over 3 minutes, and atracurium
      (0.5 mg/kg). The propofol target-controlled infusion was maintained at 1
      microgram/mL throughout surgery and stopped at skin closure. A continuous
      infusion of sufentanil at 1.8 micrograms/kg/hr was started after induction and
      reduced to 0.9 microgram/kg/hr at the start of cardiopulmonary bypass and stopped
      at the end of bypass. Atracurium was infused at a rate of 0.5 mg/kg/hr up to
      sternal closure. No inhalation agents were used. MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic data were within normal limits. Six patients (40%) responded to
      verbal commands within 15 minutes postoperatively, 10 (67%) within the first
      hour, and all patients recovered within 2 hours. Four patients (27%) resumed
      spontaneous ventilation within the first 15 postoperative minutes. The time to
      successful spontaneous ventilation was 169 +/- 42 minutes. Spontaneous
      ventilation was associated with a 21% increase in cardiac index. Total sufentanil
      dose was 328 +/- 28 micrograms (4.6 +/- 0.2 microgram/kg), whereas total propofol
      dose was 862 +/- 44 mg (13.1 +/- 1.2 mg/kg). No patient required reintubation.
      CONCLUSION: The simplicity of the method with only one change in infusion rate is
      a major advantage. The technique permits predictable recovery and return to
      spontaneous ventilation in all patients. Its use in patients entering early
      extubation protocols is appealing for its reproducibility, simplicity, and
      safety.

PMID- 9187996
TI  - Direct effects of triiodothyronine on human internal mammary artery and saphenous
      veins.
AB  - OBJECTIVE: Thyroid hormone (3,5,3'-triiodo-L-thyronine is under investigation as
      a positive inotrope and vasodilator for patients undergoing cardiac surgery. This
      study determined the direct effects of triiodothyronine on human blood vessels.
      DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in
      a university teaching hospital. PARTICIPANTS: Small excess segments of internal
      mammary arteries or saphenous veins were obtained from patients undergoing
      coronary artery bypass surgery. INTERVENTIONS: Vessel segments were cut into
      rings to measure isometric tension development in isolated tissue baths
      containing Krebs-Ringer bicarbonate solution at 37 degrees C. Rings were
      prestretched in vitro to resting tensions analogous to mean arterial or central
      venous pressures in vivo and then constricted with potassium or phenylephrine.
      Rings were exposed to increasing concentrations of triiodothyronine (4 x 10(-12)
      to 1 x 10(-4) mol/L) to obtain dose-response curves. MEASUREMENTS AND MAIN
      RESULTS: High concentrations (> or = 3.3 x 10(-5) mol/L) of trilodothyronine
      produced dose-dependent relaxation of preconstricted rings. The relaxation was
      not selective for arteries or veins at arterial resting tensions, and with either
      potassium or phenylephrine as a vasoconstrictor. Propranolol had little effect on
      subsequent triiodothyronine-induced relaxation of potassium-constricted rings at
      resting arterial tensions. CONCLUSIONS: Triiodothyronine, in supraphysiological
      and suprapharmacological concentrations, dilates preconstricted rings of human
      blood vessels in vitro; however, triiodothyronine had no demonstrable vasomotor
      effects on human internal mammary artery or saphenous vein in clinically relevant
      concentrations (10(-9) to 10(-8) mol/L). Triiodothyronine administration in vivo
      most likely has little direct effect on the tone of human vascular smooth muscle,
      particularly coronary artery bypass conduits.

PMID- 9187998
TI  - Respiratory outcomes with early extubation after coronary artery bypass surgery.
AB  - OBJECTIVE: Aortocoronary bypass surgery has undergone recent changes, promoting
      the concept of "fast tracking," in which patients are extubated and discharged
      postoperatively at an accelerated pace compared with previous historic patterns.
      Postoperative respiratory function and complications have not been previously
      studied in patients selected for "fast tracking." DESIGN: Matched retrospective
      cohort study. SETTING: Referral university teaching hospital. PATIENTS: Thirty
      one patients who were compared with a retrospective matched cohort of 112
      patients. Matching was based on forced vital capacity, age, and gender.
      INTERVENTIONS: Respiratory physiological outcomes defined as pneumonia,
      postoperative pulmonary spirometry, chest x-ray atelectasis or lobar collapse,
      and gas exchange were compared. MAIN RESULTS: The increase in atelectasis score
      compared with preoperative (0 = no atelectasis, 4 = lobar collapse) was higher (p
      < 0.01) on the day of extubation in the late extubation group (4.1 +/- 1.4)
      compared with the early extubation group (2.6 +/- 1.3). These chest radiographic
      findings were not related to pain (0 to 10 visual analog scalei, which were
      equivalent between groups (4.0 +/- 2.3 v 4.2 +/- 1.6). The decreases in
      spirometry on postoperative day 5 (FVC 1.15 +/- 0.42 v 0.86 +/- 0.54 liters; FEV1
      0.92 +/- 0.38 v 0.59 +/- 0.50 liters) were greater (p < 0.001) in the late
      extubation group. A significantly (p < 0.001) greater decrease in FEV1/FVC ratio
      in the late extubation group (3.25 +/- 0.87 v -1.6 +/- 1.11%) was indicative of
      greater airway obstruction. Fluid balance until extubation was greater in the
      late extubation group (4.0 +/- 2.1 v 1.4 +/- 1.2 liters). CONCLUSIONS:
      Differences in chest radiographs in the late extubation group at the time of
      extubation may be related to greater use of fluids or increased airway
      obstruction. The rationale of early extubation is based on cost minimization to
      decrease hospital duration. This article suggests that respiratory physiological
      outcomes are not worsened in patients who are extubated and discharged early
      after elective aortocoronary bypass surgery.

PMID- 9187999
TI  - Anesthesia for laser transmyocardial revascularization.

PMID- 9188000
TI  - High-dose esmolol and cardiopulmonary bypass for mitral valve replacement in the
      beating heart.

PMID- 9188001
TI  - Intracardiac tumor in a neonate causing complete tricuspid valve obstruction.

PMID- 9188002
TI  - Sternal spreading-triggered myocardial ischemia during surgery on a truncus
      arteriosus.

PMID- 9188003
TI  - Left atrial metastasis of a large cell carcinoma of the lung in an asymptomatic
      patient: transesophageal echocardiographic evaluation.

PMID- 9188004
TI  - Electrophysiological mechanisms for ventricular arrhythmias in patients with
      myocardial ischemia: anesthesiologic considerations, Part 1.

PMID- 9188005
TI  - Three-dimensional echocardiography.

PMID- 9188006
TI  - Case 2--1997. On-line contrast echocardiographic assessment of myocardial
      perfusion: its role in minimally invasive coronary artery bypass procedures.

PMID- 9188007
TI  - Pro: lung reduction surgery is of proven therapeutic benefit.

PMID- 9188008
TI  - Con: lung volume reductions: should we close the door before the horse leaves the
      barn?

PMID- 9188009
TI  - An unusual left ventricular transesophageal echocardiogram.

PMID- 9188010
TI  - Minimally invasive anesthesia should accompany minimally invasive surgery.

PMID- 9188011
TI  - Does D-dimer formation in patients undergoing cardiopulmonary bypass (CPB)
      reflect primary fibrinolysis?

PMID- 9188012
TI  - Recombinant hirudin is a heparin alternative in cardiac surgery.

PMID- 9188013
TI  - Dilator-associated complications of central vein catheter insertion: possible
      mechanisms of injury and suggestions for prevention.

PMID- 9188014
TI  - Dilator-associated complications of central vein catheter insertion; possible
      mechanisms of injury and suggestions for prevention.

PMID- 9188015
TI  - Dilator-associated complications of central vein catheter insertion; possible
      mechanisms of injury and suggestions for prevention.

PMID- 9188016
TI  - Dilator-associated complications of central vein catheter insertion; possible
      mechanisms of injury and suggestions for prevention.

PMID- 9188017
TI  - Minimizing excess disability: a common strategy for chronic disease management.

PMID- 9188018
TI  - Normal-pressure hydrocephalus with misleading features of irreversible dementias:
      a case report.
AB  - An 85-year-old man presented with the clinical triad (gait instability, dementia,
      and bladder and bowel incontinence), the ventriculomegaly, and the normal CSF
      pressure that characterize normal-pressure hydrocephalus (NPH). Diagnostic
      uncertainty was raised by an unusually rapid onset and a lack of initial response
      to CSF tap tests. Additionally, periodic sharp waves on EEG suggested the
      possibility of Creutzfeldt-Jakob disease, and positron emission tomography (PET)
      demonstrated a pattern of cerebral hypometabolism typical of Alzheimer's disease.
      Nevertheless, the diagnosis of NPH was supported by delayed improvement following
      CSF tap tests, and it was confirmed by a dramatic clinical recovery after CSF
      shunting, resolution of the EEG and PET abnormalities, and a normal brain biopsy.
      NPH remains one of the few reversible causes of dementia, and the presence of its
      core features, regardless of rate of onset or ancillary test results, warrants
      careful consideration of therapeutic intervention.

PMID- 9188019
TI  - Outcome of psychiatric hospitalization for very low-functioning demented
      patients.
AB  - The authors determined the outcome of geropsychiatric hospitalization for 73 very
      low-functioning demented patients (GAF score < 21). General psychiatric symptoms,
      depression, and agitation decreased significantly, and mean GAF scores increased
      significantly, with no significant change in cognitive function. Psychiatric
      hospitalization can meaningfully improve function and quality of life even in
      this very impaired population. Despite these improvements many patients are
      discharged to more restrictive settings.

PMID- 9188020
TI  - Disruptive behavior and actigraphic measures in home-dwelling patients with
      Alzheimer's disease: preliminary report.
AB  - The purpose of this preliminary report was to explore overall level and diurnal
      patterning of caregiver reports of abnormal behavior and to explore relationships
      with actigraphic measures of sleep/wake activity in Alzheimer's disease (AD)
      patients. Our primary behavioral measure was the Time-based Behavioral
      Disturbance Questionnaire (TBDQ). The overall score on this measure was shown to
      have adequate test-retest reliability and convergent validity with another
      behavioral measure. Significant correlations were obtained between the TBDQ
      overall score and actigraphically scored sleep efficiency (r = -.35, P < .05) and
      wake after sleep onset (r = .43, P < .01) in 41 subjects. The data suggest a
      moderate relationship between actigraphic measures of sleep/wake and disturbed
      behavior in home-dwelling AD patients.

PMID- 9188021
TI  - Use of clozapine to treat levodopa-induced psychosis in Parkinson's disease:
      retrospective review.
AB  - Levodopa-induced psychosis can complicate the treatment of Parkinson's disease
      (PD). In this retrospective, uncontrolled report, we describe our experience
      treating PD-related psychosis with clozapine, emphasizing those patients treated
      for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1
      year. Most patients showed a rapid improvement from baseline within 1 month using
      the Clinical Global Impression and Global Psychosis Rating Scores. Five patients
      discontinued the drug due to side effects, but only two patients reported side
      effects after 6 months of treatment. Clozapine appears to be effective in
      treating PD related psychotic symptoms while not interfering with motor function.

PMID- 9188022
TI  - Behavioral phenomenology in Alzheimer's disease, frontotemporal dementia, and
      late-life depression: a retrospective analysis.
AB  - Often patients in the early stages of Alzheimer's disease (AD), frontotemporal
      dementia (FTD), and late-life depression can be difficult to differentiate
      clinically. Although subtle cognitive distinctions exist between these disorders,
      noncognitive behavioral phenomenology may provide additional discriminating
      power. In 19 subjects with AD, 19 with FTD, 16 with late-life psychotic
      depression (LLPD), and 19 with late-life nonpsychotic depression (LLNPD),
      noncognitive behavioral symptoms were quantified retrospectively using the
      Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and compared using
      both a one-way ANOVA and a multivariate stepwise discriminant analysis, which
      utilized a jackknife procedure. The FTD group showed the highest mean total SCAN
      score, while the AD group showed the lowest. ANOVA showed significant differences
      in the mean total SCAN scores between the four diagnostic groups (P < .0001).
      With the discriminant analysis, the four disorders demonstrated different
      clusters of behavioral abnormalities and were differentiated by these symptoms (P
      < .0001). A subset of 14 SCAN item group symptoms was identified that
      collectively classified the following percentages of subjects in each diagnostic
      category: AD 94.7%, FTD 100%, LLPD 87.5%, and LLNPD 100%. These results indicate
      that AD, FTD, LLPD, and LLNPD were distinguished retrospectively by the SCAN
      without using cognitive data. Better definition of the longitudinal course of
      noncognitive behavioral symptoms in different dementias and psychiatric disorders
      will be valuable both for diagnosis and to help define behavioral syndromes that
      are associated with selective neuroanatomic and neurochemical brain pathology.

PMID- 9188023
TI  - Venlafaxine-induced reset osmostat syndrome: case of a 79-year-old depressed
      woman.
AB  - The presence of hyponatremia, especially in a frail and very old patient, is
      associated with a greater morbidity and mortality rate. We report the case of a
      depressed 79-year-old woman who was treated with venlafaxine, in whom a drug
      induced hyponatremia occurred in the absence of other possible causes. The case
      is discussed in the context of the multipotential factors that induce
      hyponatremia, with particular attention to the geriatric patient.

PMID- 9188024
TI  - Neuropsychiatric factors in the illusion of visitors among geriatric patients: a
      case series.
AB  - The 'illusion of visitors' is a common phenomenon among geriatric patients
      presenting for psychiatric or neurologic evaluation and treatment. Although these
      illusory beliefs are etiologically diverse, patients may commonly have visual
      impairment and functional and/or structural disruption of frontal and right
      hemisphere-mediated cognitive functioning. This article outlines eight cases of
      illusory beliefs among elderly patients, presenting psychiatric, neurologic,
      neuroimaging, and neuropsychological findings among these patients. Commonalities
      and differences among these cases are discussed, and a framework is provided for
      multidisciplinary assessment and treatment of patients presenting with illusory
      beliefs.

PMID- 9188025
TI  - Pain--it's all in your head: a philosophical essay.
AB  - There are three levels at which a therapist may help a patient to deal with pain.
      One is at the level of peripheral nerve endings, where pain is triggered by a
      wide variety of physical stresses which have in common the fact that living
      tissues begin to be damaged. The therapist needs to accept the patient's
      evaluation of what hurts while using objective signs to keep track of
      inflammation in the tissues and modifying the stresses of treatment so as to
      minimize pain. Higher in the nervous system, but still below consciousness there
      is a level defined by Melzack and Wall as the Gate, where there is a sort of
      triage of sensory information entering the brain. Moderate pain messages are
      crowded out when there is heavy traffic of other sensations. Patients who keep
      busy find that sensory and other distractions relieve pain. It is in the cortex,
      in the conscious mind, that pain is recognized as pain, and it is here that it is
      often made worse by fear, by anger, or by a sense of isolation. The pain may be
      diminished if the patient understands the cause and loses his fear. This is a
      great opportunity for the therapist. To be a successful pain reliever, one needs
      to be relaxed, non-threatening, and open. Patients should feel free to express
      fears and to ask questions they were too shy to ask the doctor.

PMID- 9188026
TI  - Central nervous system pathways for pain transmission and pain control: issues
      relevant to the practicing clinician.
AB  - This review considers two areas important for the clinician; ascending pathways
      for pain transmission and endogenous pain control systems. The classic three
      neuron pathway for pain transmission is presented and contrasted with more
      detailed, contemporary views on pain transmission found in the literature. The
      focus of the review is a discussion of spinal cord and brainstem pain control
      systems that modulate pain transmission. Evidence is presented which supports not
      only the existence of these pain modulation mechanisms but also that selected
      clinical procedures used by clinicians are capable of activating these mechanisms
      to control their patients' pain.

PMID- 9188027
TI  - Nociceptors and the peripheral nervous system's role in pain.
AB  - This article reviews the role that the peripheral nervous system plays in pain
      perception. The first section describes the functional properties of the primary
      sensory element-the nociceptor-and how its behavior is related to pain
      perception. The second section describes the current state of knowledge
      concerning the way our nociceptive sensing system changes as a result of tissue
      injury, including those changes related to sympathetic nervous system modulation
      of pain.

PMID- 9188028
TI  - The integration of pain sciences into clinical practice.
AB  - In the past three decades, a scientific revolution has occurred in the
      understanding of the experience of pain. However, a clinical revolution based on
      the new science is yet to occur. Pain is a multidimensional experience with many
      contributing and interacting biological/pathobiological mechanisms. These
      mechanisms may be nociceptive, peripheral neurogenic, central,
      affective/cognitive or relate to output systems such as the motor and autonomic
      nervous system. With a better understanding of pain-related neurobiology and some
      clinical decision making skills, reasoned attempts at a diagnosis of pain can be
      made. The essential question and first step related to clinical integration is to
      ask, "what is (are) the predominant mechanism(s) in a given patient's pain
      state?" This paper provides the underlying clinical biology of pain mechanisms
      and proposes pain patterns related to the mechanisms.

PMID- 9188029
TI  - Medical and pharmacologic management of upper extremity neuropathic pain
      syndromes.
AB  - Written from a neurologic and therapeutically conservative perspective, this
      review advocates fundamentally medical and pharmacologic management of upper
      extremity neuropathic pain syndromes, including chronic regional pain syndromes,
      formerly classified reflex sympathetic dystrophy (RSD) and causalgia. Mandatory
      steps include, first, a prompt serious attempt to localize the nerve lesion
      whenever possible using complete, sophisticated neurologic examinations, then
      thoughtfully selected conventional neurophysiologic and radiologic tests.
      Strongly discouraged are promiscuous use of "RSD" to describe all neuropathic
      pains, and diagnostic reliance upon thermography and uncontrolled sympathetic
      blocks. Conservative multidisciplinary diagnostic and treatment teams should
      often possess a nucleus of neurologist and hand therapist, plus additional
      consultants including psychiatric. Every physician and therapist managing
      neuropathic pain must consider psychologic and wellness issues within their
      responsibilities. Prompt referral to an experienced surgeon is crucial for
      decompression or repair of relevant, significant, objectively proven (ideally
      neurophysiologically) nerve and root lesions. Ambiguous professional
      colloquialisms, "central pain" and "central sensitization," unfortunately provide
      value-laden pretexts for premature invasive treatments, and animate the truly
      dreadful concept "central RSD". Various classes of conventional oral non-narcotic
      adjuvant analgesics are reviewed, and the inevitability of their empiric, non
      formulaic administration. No patient-specific, rationally-identifiable molecular
      receptor/switch can be deduced clinically or tripped mechanistically to terminate
      chronic pain. Two promising new non-narcotic centrally-active medications,
      gabapentin and tramadol, are highlighted as harbingers of future progress. The
      neglected subtle art of prescription writing is stressed, particularly for
      medication-sensitive patients. Medical cost containment should promote critical,
      long overdue outcomes studies comparing conservative and invasive pain
      treatments.

PMID- 9188030
TI  - The role of physical agents in modulating pain.
AB  - This article presents a review of the literature on the use of physical agents in
      modulating pain associated the hand and upper extremity musculoskeletal
      conditions. The physical agents presented include superficial heating agents,
      cryotherapy, ultrasound, and transcutaneous electrical nerve stimulation. There
      has been increased interest in modes of transdermal drug delivery, including
      iontophoresis, phonophoresis, and the application of transdermal patches.
      Treatment applications, parameters, and integration strategies are suggested. The
      purposes of this article are to review which physical agents are used to treat
      pain or inflammation and to discuss their relevant application to hand therapy
      practice. Today's health care climate requires therapists to select treatment
      strategies that are efficient, safe, and clinically effective. Although physical
      agents are widely used to manage pain in hand therapy, there is little scientific
      evidence to support their efficacy. Most information regarding the rationale for
      the use of physical agents in pain management is based on tradition, data
      extrapolated from basic science research, and uncontrolled randomized clinical
      trials. This paper discusses the need for additional research to establish
      clinical efficacy and determine optimal treatment parameters for the physical
      agents used most often to modulate pain in hand therapy.

PMID- 9188032
TI  - Myofascial pain syndromes in the upper extremity.
AB  - Myofascial pain syndromes of the upper extremity are common causes of pain that
      may follow trauma and are associated with acute or chronic musculoskeletal
      stress. The syndromes are characterized by the presence of the myofascial trigger
      point, a physical finding that is reliably identified by palpation. Local and
      referred pain are hallmarks of the syndrome, and the referred pain patterns may
      mimic such conditions as radiculopathy and nerve entrapment syndromes. Treatment
      is directed toward inactivating the myofascial trigger point, correcting
      underlying perpetuating factors, and restoring the normal relationships between
      the muscles of the affected functional motor units.

PMID- 9188031
TI  - Physical evaluation of the peripheral nervous system in disorders of pain and
      dysfunction.
AB  - In the clinical examination of a patient who is in pain, use can be made of the
      sensitization of a peripheral nerve to determine whether the disorder is
      neurogenic. Techniques of active and passive moment analysis, peripheral-nerve
      provocation tests, nerve palpation, and clinical reasoning are used in the
      evaluation. The technique is described and a case study is presented to support
      its use.

PMID- 9188033
TI  - Reflex sympathetic dystrophy: the clinician's perspective.
AB  - Theories on the etiology of reflex sympathetic dystrophy (RSD) are reviewed and
      presented in three categories: peripheral, spinal, and supraspinal. The
      peripheral pathophysiology involves a prolonged inflammatory, response to injury
      due to the axon reflex with release of vasoactive neuropeptides and sensitized
      nociceptors. The spinal component of RSD genesis involves nociceptive spinal cord
      neurons with lowered thresholds due to chronic pain input. These sensitized
      spinal neurons respond in turn by signaling pain reflexes through the sympathetic
      system. A physical-emotional diathesis may predispose individuals to respond to
      stress through autonomic arousal. Autonomic arousal, coupled with injury, signals
      the supraspinal influence on this syndrome. Since the puzzle of RSD remains to be
      solved, measurement and treatment strategies are suggested to provide
      intervention at each level. Measurement techniques should include a battery of
      static tests and stress tests. Static tests are used to quantify a physiological
      parameter at one point in time. Stress tests access physiological response to
      various neuro-vaso-motor challenges. A "hands off" treatment regime is presented
      that includes pain control, methods to reset sensory thresholds, vasomotor
      challenges, and an active motion program.

PMID- 9188034
TI  - Repetitive use and static postures: a source of nerve compression and pain.
AB  - Nerve compression or musculoskeletal diagnoses require consideration of both the
      repetitive movements and static postures that may be contributing to the problem.
      Certain postures and positions assumed at home, at work, and during sleep will
      have three major influences: (1) directly increasing pressure on nerves at
      entrapment sites; (2) placing muscles in shortened positions so that adaptive
      muscle shortening may then secondarily compress nerves; and (3) placing some
      muscles in elongated and weakened positions, resulting in other muscles being
      over-used, thus creating the cycle of muscle imbalance. Successful management of
      the patient with upper extremity pain, paresthesia, and numbness should begin
      with initial identification of all sites that are contributing to the presenting
      symptoms. Treatment must then be directed toward the sources of nerve compression
      and musculoskeletal dysfunction. Upper quadrant symptomatology can be alleviated
      with an appropriate therapy program, even in the patient with chronic symptoms,
      but only with patient education, compliance with an exercise program, and
      behavioral modification at home, work, and during sleep.

PMID- 9188035
TI  - The neural consequences of repetition: clinical implications of a learning
      hypothesis.
AB  - Repetitive strain injuries (RSIs) are difficult to treat. Some individuals with
      RSIs may ultimately develop chronic pain syndromes or movement problems like
      focal hand dystonia (FDh), a disorder of motor control manifested in a specific
      context during skilled, hand tasks. This paper reports on the results of four
      neuroplasticity studies suggesting that repetitive hand opening and closing can
      lead to motor control problems, measurable somatosensory changes, and problems in
      graphesthesia and stereognosis. The experiments support a learning hypothesis for
      the origin of severe RSIs, particularly FDh. This degradation in the sensory
      representation of the hand may not only explain the therapeutic challenge of
      returning these patients to work, but also provide a foundation for developing
      more effective physical rehabilitation strategies. Implications and conjectures
      for the applications of this learning hypothesis to conditions of chronic pain
      are also discussed.

PMID- 9188036
TI  - Pain management programs in hand therapy: a literature review and appraisal.
AB  - This article analyzes literature on pain management programs in hand therapy.
      Philosophical and practical issues that may influence the approach to pain are
      reviewed. Possible explanations for the relative lack of
      interdisciplinary/comprehensive approaches to pain are put forth. Conditions
      under which more comprehensive treatment should be considered are discussed.

PMID- 9188037
TI  - Psychological influences on pain perception and non-pharmacologic approaches to
      the treatment of pain.
AB  - Pain is a complex process, in part because it is mediated by so many different
      variables. However, because pain is the primary reason for seeking medical
      treatment and often a barrier to compliance, therapists treating painful
      disorders or injuries need to be familiar with those factors that influence pain
      perception and treatment approaches. How individuals perceive pain, and hence how
      clinicians treat it, depends upon a wide variety of psychosocial factors,
      including mood, age, gender, expectations, social support, and perceptions of
      control. Even the manner with which therapists interact with patients can
      minimize the pain experience and ultimately impact compliance and recovery rates.
      This paper overviews the multifaceted nature of pain by outlining how psychologic
      variables impact pain experiences. In addition, this article reviews a number of
      nonpharmacologic techniques and approaches (i.e., distraction, imagery,
      relaxation, biofeedback) that are available for assisting patients in dealing
      with pain.

PMID- 9188038
TI  - Terminal dUTP nick end labeling (TUNEL) positive cells in the different regions
      of the brain in normal aging and Alzheimer patients.
AB  - This study investigated terminal dUTP nick-end labeling (TUNEL)-positive cells in
      the frontal, occipital, and hippocampal cortices of seven normal aging and four
      Alzheimer's patients. Significant increase in TUNEL-positive cells was observed
      in the frontal and hippocampal cortices of Alzheimer's patients when compared
      with controls. In the hippocampal cortex, only area CA4 demonstrated a
      significant increase of TUNEL-positive cells. Double staining of TUNEL-positive
      cells for glial fibrillary acidic protein revealed that < 13% of the TUNEL
      positive nuclei belonged to astrocytes. The results of this study illustrated a
      differential pattern of cortical degeneration between normal aging and Alzheimer
      patients.

PMID- 9188039
TI  - delta 9-Tetrahydrocannabinol increases activity of tyrosine hydroxylase in
      cultured fetal mesencephalic neurons.
AB  - The exposure of pregnant rats to delta 9-tetrahydrocannabinol (delta 9-THC), the
      main psychoactive constituent of Cannabis sativa, during gestation and lactation,
      affects the gene expression and the activity of tyrosine hydroxylase (TH) in the
      brain of their offspring, measured at fetal and early postnatal ages, when the
      expression of this enzyme plays an important role in neural development. In the
      present article, we have examined whether delta 9-THC is able to affect TH
      activity in cultured mesencephalic neurons obtained from fetuses at gestational d
      14. Thus, TH activity increased approximately twofold in cells obtained from
      naive fetuses when exposed for 24 h to medium containing delta 9-THC. In
      addition, TH activity was also approx twofold higher in cells obtained from
      fetuses exposed daily to delta 9-THC from d 5 of gestation than in cells obtained
      from control fetuses, when both were exposed to basal media. This effect of delta
      9-THC on TH activity seems to be produced via the activation to cannabinoid
      receptors, in particular the CB1 subtype, which would presumably be located in
      these cells. This is because the exposure to medium containing both delta 9-THC
      and SR141716A, a specific antagonist for CB1 receptors, abolished the effect
      observed with delta 9-THC alone. SR141716A alone was without effect on TH
      activity. Collectively, our results support the notion that delta 9-THC increased
      TH activity in cultured mesencephalic neurons, as previously observed in vivo,
      and that this effect was produced by activation of CB1 receptors, which seem to
      be operative at these early ages. All this points to a role for the endogenous
      cannabimimetic system in brain development.

PMID- 9188040
TI  - Dlx-2 homeobox gene controls neuronal differentiation in primary cultures of
      developing basal ganglia.
AB  - Homeodomain-containing genes of the Dlx family are expressed in the developing
      basal ganglia. To investigate the role of Dlx genes during development, we
      studied their cellular localization in primary cultures of embryonic basal
      telencephalon, and examined the changes in cellular phenotypes resulting from
      blockade of Dlx-2 expression. Cells containing Dlx-1, Dlx-2, and Dlx-5 mRNAs are
      immature cells of the neuronal lineage expressing the microtubule-associated
      proteins (MAPs) MAP1B and MAP2, but not glial fibrillary acidic protein (GFAP).
      Treatment of these cells with antisense oligonucleotides targeted to Dlx-2 caused
      a specific decrease of Dlx-2 mRNA and protein. This decrease in the Dlx-2 gene
      product was associated with a decrease in the expression of MAP2, a protein
      localized in neuronal dendrites, along with a smaller decrease in the 200-kDa
      neurofilament subunit (NF-H). Proteins expressed preferentially in axons were
      unchanged. This reduction in MAP2 expression was associated with a decrease in
      dendrite outgrowth and an increased level of cell proliferation. None of these
      changes were elicited by antisense oligonucleotides targeted to Dlx-1. We suggest
      that the Dlx-2 gene product regulates two interrelated aspects of neuronal
      differentiation: the exit from the mitotic cycle and the capability to grow MAP2
      positive dendrites. As such, this gene product may be important for the
      establishment of neuronal polarity, setting the stage for afferent synaptic
      connectivity.

PMID- 9188041
TI  - Culture density regulates both the cholinergic phenotype and the expression of
      the CNTF receptor in P19 neurons.
AB  - The P19 embryonal carcinoma cells differentiate into neurons, astrocytes, and
      fibroblast-like cells following induction with retinoic acid. The cells mature
      into functional neurons, as determined by their ability to release
      neurotransmitters in a Ca(2+)- and depolarization-dependent manner. P19 neurons
      in culture represent a mixed population in terms of their neurotransmitter
      phenotype. The cholinergic phenotype of these neurons is modulated by culture
      density. Cholinergic markers, such as the vesicular acetylcholine transporter,
      acetyl cholinesterase, and choline acetyltransferase, are expressed in about 85%
      of the cells in sparse cultures and are largely suppressed at high cell
      densities. In contrast, glutamate release is enhanced in dense P19 neuronal
      cultures. The factor mediating the density effect is concentrated exclusively on
      the cell membrane of P19 neurons and not on the nonneuronal cells, which also
      differentiate from P19 embryonal carcinoma cells. This membrane-associated
      component retains its functionality, even after membrane fixation. The
      downregulation of the cholinergic properties in dense cultures is paralleled by a
      downregulation of the alpha subunit of the ciliary neurotrophic factor (CNTF)
      receptor. Thus, it is suggested that the membrane-associated factor, which
      mediates the density effect, downregulates the cholinergic phenotype by
      inhibiting the responsiveness of these neurons to CNTF. We further suggest that
      the P19 cell line can serve as a model system for the study of neurotransmitter
      phenotype acquisition and plasticity throughout neuronal differentiation.

PMID- 9188042
TI  - Myocyte-specific enhancer binding factor 2C expression in fetal mouse brain
      development.
AB  - We have previously found that myocyte-specific enhancer binding factor 2C (MEF2C)
      is expressed in the brain, where it is found at high levels in the developing
      cerebral cortex. We have now examined MEF2C expression in fetal mouse brain by in
      situ hybridization and by immunohistochemistry from E11 to E17, the period when
      most cortical neurons are born. The distribution of MEF2C mRNA detected by in
      situ hybridization closely resembles that of MEF2C immunoreactivity. MEF2C is not
      present in proliferative zones in the brain. It is present at high levels in
      cells that have migrated to the subplate and cortical plate. MEF2C is also found
      in the olfactory blub at high levels and at lower levels in hippocampus, basal
      forebrain, striatum, cerebellum, and inferior colliculus, and in some nuclei of
      the hypothalamus, thalamus and brainstem. The pattern of expression suggests that
      MEF2C is expressed in a subset of postmitotic neurons in the brain and that it
      may therefore function to promote terminal differentiation of the cells that
      express it.

PMID- 9188044
TI  - Cloning and identification of human syntaxin 5 as a synaptobrevin/VAMP binding
      protein.
AB  - Syntaxins are transmembrane proteins that function in regulating transport
      vesicle docking and fusion with target membranes in neuronal and nonneuronal
      cells. Vesicle docking is thought to be regulated in part by the specific
      interactions of syntaxin with a vesicle-associated membrane protein termed
      synaptobrevin/VAMP. We have cloned a 1557-bp cDNA that encodes the human syntaxin
      5 isoform, using a combination of PCR and colony-screening methods. The deduced
      301 amino-acid sequence of human syntaxin 5 shares 96% identity with rat syntaxin
      5. Like rat syntaxin 1A, human syntaxin 5 binds to synaptobrevin/VAMP in vitro.
      The identification of human syntaxin 5 as a synaptobrevin/VAMP-binding protein
      supports the hypothesis that syntaxin 5 regulates protein transport by binding to
      vesicle-associated membrane proteins.

PMID- 9188043
TI  - Steroid hormone receptors activate transcription in glial cells of intact retina
      but not in primary cultures of retinal glial cells.
AB  - We have compared the steroid responsiveness of Muller glial cells of intact
      embryonic chicken retina with that of primary cultures derived from Muller glia.
      Appropriately constructed fusion genes were found to be highly glucocorticoid
      inducible after their cotransfection with an expression vector encoding the human
      glucocorticoid receptor (GR) into intact embryonic d-10 (E10) or E5.5 retina.
      Dramatically attenuated inductions were obtained after contransfection of Muller
      cell primary cultures. The progesterone receptor (PR) was also demonstrated to
      function in intact retina, but not in Muller cell primary cultures. An
      immunochemical assay was utilized to confirm that a glucocorticoid-responsive,
      beta-galactosidase-encoding fusion gene was specifically induced in Muller cells
      after its transfection into intact retina. Thus, in contrast to Muller cells in
      intact retina, Muller cells in primary culture have lost the capacity to achieve
      transcriptional activation by steroid receptors. We postulate that coordinate
      expression of the GR, and other more general factors required for steroid
      inducibility, is lost by dispersion and primary culture of retinal Muller glial
      cells.

PMID- 9188045
TI  - Solid-state stability of human insulin. II. Effect of water on reactive
      intermediate partitioning in lyophiles from pH 2-5 solutions: stabilization
      against covalent dimer formation.
AB  - Previous studies have established that at low pH human insulin decomposition
      proceeds through a two-step mechanism involving rate-limiting intramolecular
      formation of a cyclic anhydride intermediate at the C-terminal AsnA21 followed by
      intermediate partitioning to various products, most notably desamido insulin and
      covalent dimers, in both aqueous solution and in the amorphous (lyophilized)
      solid state. This study examines the product distribution resulting from insulin
      degradation in lyophilized powders as a function of water content and the phase
      behavior of the solid (glassy versus rubbery) between pH 3 and 5. In amorphous
      solids at low water content (glassy state), the cyclic anhydride intermediate of
      insulin reacts predominantly with water to form deamidated insulin, whereas the
      intermolecular reaction with another insulin molecule to form a covalent dimer
      accounts for < or = 15% of the total degradation. Increasing water content
      reduces the glass transition temperature of insulin to < 35 degrees C, and
      covalent dimer formation becomes increasingly favored relative to deamidation. An
      increase in solid-state pH also favors dimerization as deprotonation of the
      terminal amino groups of insulin renders them more nucleophilic. Covalent
      dimerization was almost totally suppressed by incorporation into a glassy matrix
      of trehalose, which both minimizes molecular mobility and physically separates
      the insulin molecules. The kinetics and product distribution of human insulin in
      lyophilized powders between pH 3 and 5 illustrate the differential sensitivities
      of various solid-state reaction types to the effects of water activity and solid
      phase behavior. The intramolecular cyclization at the AsnA21 position requires
      only short-range conformational flexibility and thus is only modestly restricted
      even in the glassy state. On the other hand, the competing bimolecular reactions
      involving either water or another molecule of insulin combining with the
      intermediate anhydride are dependent on molecular mobility of the reactants, in
      accord with predictions of free volume theory. In the glassy state, deamidation
      (reaction with water) is favored because of the restricted molecular mobility of
      proteins in rigid matrices. Increasing plasticization with increasing water
      content favors covalent aggregate formation because of the higher dependence of
      protein mobility on free volume within the solid matrix.

PMID- 9188046
TI  - Production and characterization of polyclonal anti-S 20499 antibodies: influence
      of the hapten structure on stereospecificity.
AB  - Immunoassays were studied as an alternative to HPLC methods for the
      stereoselective determination of a chiral drug, S 20499, a new anxiolytic
      compound that is chemically related to buspirone. The production of highly
      stereospecific polyclonal antibodies was sought following the construction of
      appropriately optimized hapten-protein conjugates. This process involved the
      selection of the structure and the length of the spacer arm used to couple S
      20499 to the carrier protein as well as deciding on the location of the coupling
      site with respect to the chiral center. Two haptens were prepared: one a
      derivative resembling the original structure of S 20499, with the effective
      addition of a carboxylic acid group, and a second with the effective addition of
      a butanoic acid moiety that is supposed to favor stereorecognition. Six
      stereospecific polyclonal antisera were obtained in rabbits with two groups of
      antibody families defined in terms of specificity. Both approaches gave high
      levels of stereospecificity (cross-reactivity towards the optical antipode of S
      20499 ranged from 4.1% to < 0.1%). Although it did not decrease the mean apparent
      affinity constant, the longer spacer improved antibody specificity by decreasing
      cross-reactions towards dealkylated S 20499 derivatives. Hence, the addition of a
      four carbon atom bridge should be a valuable tool for increasing antibody
      stereospecificity with no drawbacks in terms of specificity and affinity. It was
      also shown that long immunization periods appear to have no effect on the
      stereospecificity of the antibodies obtained.

PMID- 9188047
TI  - Diffusion of drugs in native and purified gastrointestinal mucus.
AB  - The mucus layer covering the surface of the gastrointestinal tract may act as a
      barrier to drug absorption. The aim of this investigation was to study the self
      diffusion coefficients of model drugs with different physicochemical properties
      in gastrointestinal mucus. An in vitro method was used to determine the self
      diffusion coefficients of radiolabeled model drugs in different diffusion media.
      Glucosamine, mannitol, glucuronic acid, glucose, metoprotol, antipyrine,
      propranolol, hydrocortisone, and testosterone, which display large differences in
      charge and octanol/water distribution ratios (K), were used as model drugs. The
      diffusion coefficients of model drugs were compared in phosphate buffer (PB),
      native pig intestinal mucus (PIM), and purified pig gastric much (PPGM). PIM was
      not purified and therefore contained all the original components of native mucus,
      whereas PPGM contained only high molecular weight mucin molecules. Charge had
      only minor effects on the diffusion coefficients of the model drugs.
      Lipophilicity, however, had a much larger effect, the largest decrease in
      diffusion coefficient, 58%, was observed for testosterone in PIM. A negative
      relationship between the diffusion coefficient and log K was observed in PIM, but
      no relationship was observed in PPGM and PB. In contrast, the diffusion
      coefficients for two larger molecules of comparable size, the lipophilic peptide
      cyclosporin and the hydrophilic peptide D-arginine vasopressin, were markedly
      reduced in PIM. In conclusion, the most important physicochemical characteristic
      influencing the diffusion coefficient of most drugs in gastrointestinal mucus
      appears to be lipophilicity, whereas molecular size appears to have more
      influence for larger peptide drugs.

PMID- 9188048
TI  - Size and conformational stability of the hepatitis A virus used to prepare VAQTA,
      a highly purified inactivated vaccine.
AB  - A variety of biophysical techniques have been employed to examine the size and
      conformational integrity of highly purified hepatitis A virus (HAV) in solution
      (purified HAV particles are subsequently formalin-inactivated and adsorbed to
      aluminum salts for use as the vaccine VAQTA). The size of HAV particles was
      assessed by a combination of electron microscopy, sedimentation velocity, and
      dynamic light scattering. The effect of ionic strength and temperature on the
      overall conformational stability of HAV was determined by a combination of
      intrinsic HAV protein fluorescence, fluorescent probes of both RNA and protein,
      and UV-visible spectroscopy. A major structural change in HAV occurs near 60
      degrees C with the addition of 0.2 M magnesium chloride enhancing the thermal
      stability of HAV by approximately 10 degrees C. Salt concentrations above 0.2 M,
      however, decrease the solubility of HAV. The effect of pH on the physical
      properties of HAV particles was monitored by dynamic light scattering, analytical
      size exclusion HPLC, and interaction with fluorescent dyes. HAV particles undergo
      a substantially reversible association/aggregation at pH values below 6 with the
      concomitant exposure of previously buried hydrophobic surfaces below pH 4. These
      results are in good agreement with previous studies of HAV thermal stability
      under extreme conditions in which the irreversible inactivation of the viral
      particles was measured primarily by the loss of viral infectivity. The wide
      variety of biophysical measurements described in this work, however, directly
      monitor structural changes as they occur, thus providing a molecular basis with
      which to monitor HAV stability during purification and storage.

PMID- 9188049
TI  - Binary system of (R)- and (S)-nitrendipine--polymorphism and structure.
AB  - Three monotropically related modifications of (RS)-nitrendipine (RS-NTD) were
      investigated. With the aid of the optical antipodes of NTD, it was possible to
      construct a binary phase diagram, from which it is obvious that the
      thermodynamically stable mod. I of RS-NTD (mp 156-158.5 degrees C, heat of fusion
      41.1 +/- 0.2 kJ mol-1) is a racemic compound, while mod. II (mp 130-134 degrees
      C, heat of fusion 29.4 kJ mol-1) and mod. III (mp 124-126 degrees C, heat of
      fusion 27.2 kJ mol-1) occur as conglomerates of different modifications of R- and
      S-NTD. The eutectic points (calculated) are at 150 degrees C and at 19% and 81%
      molar fraction of an enantiomer, respectively. Two modifications of the
      enantiomers are characterized (En-mod. I, thermodynamically stable form, mp 156
      158 degrees C, heat of fusion 34.5 +/- 1.3 kJ mol-1 and En-mod. III, mp 121
      degrees C), whereas a third modification (En-mod. II) must be hypothesized
      pursuant to the phase diagram (mp ca. 152 degrees C). IR spectra, DSC curves, and
      X-ray powder diffractograms of the different phases are described. The crystal
      structure of the enantiomer En-mod. I is reported (monoclinic, P2(1), density
      1.346 g cm-3) and compared with the X-ray structure of the racemic compound
      (monoclinic, P2(1)/c, density 1.356 g cm-3). A comparison with similar studies on
      nimodipine has been made to emphasize the parallels to a substance of this
      chemical group.

PMID- 9188050
TI  - Iontophoretic transport across a synthetic membrane and human epidermal membrane:
      a study of the effects of permeant charge.
AB  - The effects of permeant charge (z) on iontophoretic-enhanced transport were
      investigated with synthetic Nucleopore membranes and with human epidermal
      membranes using a four-electrode potentiostat with side-by-side diffusion cells.
      The modified Nernst-Planck model (Nernst-Planck theory with an additional
      transport term to correct for the effect of the convective solvent flow due to
      electroosmosis) was first examined in a Nuclepore membrane system with model
      permeants calcein (z = -4), salicylate (z = -1), and a series of polystyrene
      sulfonates (from monomer to molecular weight of approximately 8000 with a z range
      of -1 to approximately -40). The flux enhancement (E) for each permeant was
      determined at 470 mV. Mannitol (a neutral molecule) was used as a probe to
      determine a correction for convective solvent flow under the same applied voltage
      conditions. Good agreement between the experimental results and the predictions
      from the modified Nernst-Planck model was found for calcein, salicylate, and
      polystyrene sulfonates up to molecular weight of approximately 1800 (z
      approximately -8). The flux enhancements for the higher molecular weight
      polystyrene sulfonates with greater z values were more than a factor of three
      lower than theoretical predictions; the electrophoretic effect and counterion
      binding to the permeants are proposed as possible explanations for these
      discrepancies between experiment and the modified Nernst-Planck theory. In the
      studies with human epidermal membranes, iontophoretic flux enhancements for
      calcein, salicylate, and taurocholate were determined at 250 and/or 470 mV. The
      flux enhancements were generally consistent with the results calculated from the
      modified Nernst-Planck model.

PMID- 9188051
TI  - Methods to compare dissolution profiles and a rationale for wide dissolution
      specifications for metoprolol tartrate tablets.
AB  - The objectives of this work were to apply several profile comparison approaches
      to dissolution data of four different but bioequivalent metoprolol tartrate
      tablet formulations to (1) identify the advantages and disadvantages of each
      approach, (2) quantify the metric for comparing dissolution profiles of each
      method, (3) determine metric limits that are consistent with the observed
      bioequivalence, and (4) rationalize the observed metric limits with respect to
      the role of dissolution in overall metoprolol absorption. Dissolution was
      performed by the USP monograph method on four formulations of metoprolol tartrate
      tablets (Lopressor plus fast, medium, and slow dissolving test formulations).
      Three general approaches to compare dissolution profiles were examined; they were
      ANOVA-based, model-independent, and model-dependent approaches. It is concluded
      that model-independent approaches and several model-dependent approaches yielded
      numerical results that can serve as objective and quantitative metrics for
      comparing entire dissolution profiles of the four metoprolol tartrate
      formulations. However, these methods presented complications. Some metrics were
      dependent on the length of the dissolution profile and the sampling scheme.
      Results from the pairwise procedures also depended on the pairing assignment of
      individual profiles. In spite of complications, these methods suggested wide
      dissolution specification limits. Wide dissolution specifications were
      rationalized through an analysis of in vitro-in vivo relationships, which
      indicated metoprolol dissolution from these formulations was not the rate
      limiting step; hence, a range of dissolution profiles can be expected to yield
      equivalent plasma profiles.

PMID- 9188052
TI  - Perifollicular transgenic expression of human interleukin-1 receptor antagonist
      protein following topical application of novel liposome-plasmid DNA formulations
      in vivo.
AB  - Expression plasmid DNA for the human interleukin-1 receptor antagonist (IL-1ra)
      protein was formulated with nonionic:cationic (NC) liposomes or
      phosphatidylcholine:cationic (PC) liposomes and applied to the auricular skin of
      hamsters in single- and multiple-dose protocols. Confocal microscopy identified
      delivery of plasmid DNA proximal to perifollicular cells, and successful
      transfection of perifollicular cells was identified by immunohistochemistry and
      ELISA. Skin treated for 3 days with the NC liposomes had statistically
      significant levels of transgenic IL-1ra present for 5 days post-treatment.
      Expression of transgenic IL-1ra was specific to areas of skin treated with NC
      liposomes but not PC liposomes. The results indicate that the NC liposomes can
      deliver expression plasmid DNA to perifollicular cells and mediate transient
      transfection in vivo.

PMID- 9188053
TI  - Exponential heating in drug stability experiment and statistical evaluation of
      nonisothermal and isothermal prediction.
AB  - A new nonisothermal heating model (exponential heating model) for drug stability
      experiments, based on a theoretical study of simulated nonisothermal data, is
      presented. In the model, the heating rate dT/dt is increased by 2-4 times at
      every increase of 10 degrees C in temperature: dT/dt = a(T-T0)/10.(dT/dt)0 where
      a is the times by which the heating rate is increased at every increase of 10
      degrees C. A computation method with optimization and Simpson integration for the
      experiment was also introduced. The estimates for the shelf-life and activation
      energy obtained by the exponential and other nonisothermal heating models were
      statistically evaluated and were compared with those obtained by the isothermal
      method under various conditions. The results indicated that under the same
      experimental conditions, the estimates obtained by the exponential heating model
      were significantly more accurate and precise than those obtained by the linear,
      reciprocal, and logarithmic heating models. The accuracy and precision of the
      estimates were independent of the shelf-life of drugs and experimental period.
      The estimates obtained by the isothermal method were somewhat more accurate and
      precise than those obtained by the exponential heating model. However, the
      experimental period needed by the isothermal method was about five times longer
      than that needed by the exponential heating model. The results also showed that
      in each of the heating models, the estimates are more accurate and precise by
      increasing the extent of drug degradation, changing temperature range or sampling
      frequency, or by having the mean temperature closer to room temperature. To
      demonstrate its applicability, the exponential heating model was used to study
      the stability of vitamin C tablets and predict their shelf-life.

PMID- 9188054
TI  - Influence of alpha-cyclodextrin and hydroxyalkylated beta-cyclodextrin
      derivatives on the in vitro corneal uptake and permeation of aqueous pilocarpine
      HCl solutions.
AB  - Interactions in aqueous solution between pilocarpine hydrochloride (P-HCl), a
      rather hydrophilic drug with good water solubility, and various cyclodextrins
      (CDs) were described recently. To assess the influence of CDs on the diffusion
      behavior of pilocarpine, in vitro studies were performed using porcine or bovine
      corneas as diffusion barriers. The affinity of P-HCl for porcine cornea in the
      presence of alpha-cyclodextrin (alpha-CD) and (hydroxyethyl)-beta-cyclodextrin
      (HE-beta-CD) was determined by drug uptake experiments. Additionally, in vitro
      permeation experiments through bovine corneas were conducted with a modified
      diffusion device optimized for corneal perfusion studies. The results obtained
      from the corneal uptake studies indicate that the addition of alpha-CD led to
      increased tissue drug levels. The increase in permeability of pilocarpine in the
      presence of alpha-CD was approximately 10-fold (log Papp = -4.87 +/- 0.03) in
      comparison with plain P-HCl solution (log Papp = -5.89 +/- 0.06). Permeation
      studies with corneas pretreated with alpha-CD solution revealed enhanced corneal
      permeability of pilocarpine due to alpha-CD induced membrane effects. The
      hydroxyalkylated beta-CD derivatives HE-beta-CD (log Papp = -6.27 +/- 0.09) and
      (hydroxypropyl)-beta-cyclodextrin (HP-beta-CD; log Papp = -6.40 +/- 0.03),
      however, seemed to cause slightly decreased permeation rates, supporting the
      concept of an interaction between pilocarpine and the hydroxyalkylated-beta-CD
      derivatives. Considering physiological compatibility, the addition of CDs seems
      to be an effective tool to modify and optimize the ocular availability of
      pilocarpine.

PMID- 9188055
TI  - Evaluation of properties of apigenin and [G-3H]apigenin and analytic method
      development.
AB  - This study provides baseline data and analytical methods to assist in the
      evaluation of apigenin, a plant flavonoid with promising chemopreventive activity
      against skin cancer. Apigenin was freely soluble in dimethylsulfoxide (> 100
      mg/mL), but it had low solubility (0.00135-1.63 mg/mL) in all the other solvents
      and surfactants tested, especially in highly hydrophilic or nonpolar solvents.
      The partition coefficient (log K) calculated from the solubility ratio of
      apigenin in n-octanol and water was 2.87. Apigenin strongly absorbed UV light,
      with three maximum absorption wavelengths at 212, 269, and 337 nm (epsilon =
      29,800, 19,020, and 18,930 M-1 cm-1, respectively). Using quercetin as the
      internal standard, a reversed-phase HPLC method was developed to quantitatively
      analyze apigenin in epidermal cells obtained from SENCAR mice. Apigenin was
      labeled at position 6, 8, 3', and 5' with tritium by a platinum-catalyzed proton
      tritium exchange as confirmed indirectly by 1H NMR analysis of the deuterated
      apigenin. The tritium label was stable in aqueous environments, especially under
      acidic and neutral conditions, so [G-3H]apigenin was considered suitable for
      subsequent absorption and metabolic studies.

PMID- 9188056
TI  - Modeling dissolution of sparingly soluble multisized powders.
AB  - The dissolution of powder drugs, besides being a topic of utmost importance,
      especially for the sparingly soluble ones, is far from being well-explained. The
      purpose of the present study is, on the one hand, to obtain experimental
      dissolution profiles and, on the other hand, to analyze and process the data for
      dissolution modeling. Three different size fractions of a widely used sparingly
      soluble drug--ibuprofen--were fully characterized with regard to its particle
      size distribution, specific surface area, density, solubility, and diffusion
      coefficient. The dissolution profiles were obtained making use of a technique
      that counts and sizes particles--the Coulter counter technique--which is capable
      of following the number and size of the particles in suspension throughout time.
      The knowledge of these parameters allowed a critical study of the assumptions
      associated with the models currently used to describe the dissolution process. It
      was concluded that most of the assumptions were not valid for the present
      experimental conditions. This motivated the proposal of a new methodology, which
      uses the experimentally determined characteristics of the drug and takes into
      account the polydisperse nature of the powder. By applying an adequate
      dissolution equation to each of the many size classes in which the primary
      particle size distribution was divided, it was possible to obtain a large
      agreement between the simulated and the experimental dissolution profile.

PMID- 9188057
TI  - Validation of procedures for quantitative whole-body autoradiography using
      digital imaging.
AB  - The objective of this study was to demonstrate that tissue concentrations of
      radioactivity derived by digital analysis of autoradiograms were comparable to
      values derived from direct sampling and analysis of tissues. In addition, we
      describe the preparation and calibration of standards for use in quantitative
      whole-body autoradiography. For this study, three male Long-Evans hooded rats
      were administered 14C radioactivity intravenously. The animals were sectioned for
      whole-body autoradiography, with concomitant sampling of blood and 16 selected
      tissues. After 3 weeks of film exposure, the optical densities of the resulting
      autoradiograms were analyzed with a RAS3000 digital imaging system to estimate
      tissue concentrations of radioactivity. These concentrations were then compared
      with those obtained by direct analysis of the tissue samples. The concentrations
      derived from digital analysis of the autoradiograms were very highly correlated
      with those determined from direct tissue analysis (r = 0.956). Linear regression
      analysis yielded a straight line with a slope of 0.97 and a goodness of fit (r2)
      of 0.913. This analysis suggested that there is an approximate 1:1 correlation
      between concentration values determined by the two methods. Marked differences
      between the values derived via the two techniques were observed for only three
      tissues. However, this subset of the data accounted for only 6% of the total
      data, and the differences were probably due to contamination from adjacent
      tissues during excision. Overall, the concentrations of radioactivity derived
      from digital analysis of the autoradiograms were comparable to those derived from
      direct analysis of tissue samples. The results indicated that the digital
      analysis procedure for film can serve as a valuable adjunct to conventional
      tissue analysis for radioactivity.

PMID- 9188058
TI  - Maintaining a near zero-order drug delivery from minidose reservoirs:
      simultaneous drug diffusion and binary vehicle evaporation.
AB  - The purpose of this study was to develop a new design for transdermal system that
      provides a nearly constant drug delivery rate for the desired period of time in
      the absence of a large excess of drug in the donor reservoir. Simultaneous drug
      diffusion and aqueous binary vehicle evaporation has been investigated as a means
      of maintaining constant drug delivery from minidose reservoirs. Benzocaine was
      used as the model drug and water-ethanol mixtures as the binary vehicles.
      Benzocaine is much more soluble in ethanol than in water. Simultaneous diffusion
      evaporation experiments were conducted using the water-ethanol mixture saturated
      with benzocaine as the minidose-reservoir. The reservoir vehicle was allowed to
      evaporate through a permselective membrane so as to maintain drug saturation in
      the vehicle even though the drug mass in the donor reservoir was constantly
      decreasing. Saturation activity of drug is maintained during donor depletion of
      drug by the selective loss of alcohol from the donor solvent, which concomitantly
      lowers the solubility. The superiority of the evaporable binary vehicle over a
      conventional sealed system was demonstrated by achieving near zero-order drug
      delivery with minimum drug remaining. A theoretical model was developed to
      predict drug flux, drug amount delivered, reservoir solvent volume and
      composition, and drug solubility during the two simultaneous processes of drug
      release and preferential solvent evaporation. Experimental data are in good
      agreement with theoretical calculations.

PMID- 9188059
TI  - Swelling of and drug release from monoglyceride-based drug delivery systems.
AB  - Depending on the water content, unsaturated monoglycerides form various liquid
      crystalline phases, which can be used as sustained-release carriers. The aim of
      this study was to investigate the water uptake of and drug release from melt
      congealed monoglyceride-based drug carriers. The water uptake of the unsaturated
      monoglycerides monoolein and monolinolein followed second-order swelling kinetics
      and levelled off at about 50% water content, at which a highly viscous cubic
      phase was formed. The rapid formation of the cubic phase suggested that the drug
      release occurred mainly from this phase. The drug release followed the square
      root of time relationship during the initial release phase. Chlorpheniramine
      maleate, an amphiphilic drug was not completely released because of binding to
      the cubic phase. The rate of water uptake increased and the maximum water uptake
      decreased with increasing temperature. The drug release could be controlled by
      varying the surface-to-volume ratio, the drug loading, and the water content of
      the lipid matrix. It was independent of the source of monoolein.

PMID- 9188060
TI  - Expression of human polyspecific renal organic cation transport activity in
      Xenopus laevis oocytes.
AB  - Polyspecific organic cation transporters in the basolateral and brush border
      membrane of the kidney play a role in the elimination of many clinically
      important drugs and endogenous compounds. In this study we report the functional
      expression of organic cation transport activity in Xenopus laevis oocytes
      injected with poly(A)+RNA (mRNA) isolated from human kidney. Uptake of
      [14C]tetraethylammonium (TEA) was measured in mRNA-injected or water-injected
      oocytes, 4 days after injection. In oocytes injected with 50 ng of mRNA isolated
      from human renal cortex, the uptake of [14C]TEA was significantly increased in
      comparison with water-injected oocytes (7.2 +/- 0.6 and 3.5 +/- 0.3
      pmol/oocyte/h, respectively). Injection of 20 ng of an enriched size-fraction
      (fraction C) of mRNA (mean size of 2.3 kb) resulted in further enhancement of
      [14C]TEA uptake: [14C]TEA uptake was enhanced six-to seven-fold in oocytes
      injected with fraction C (23.7 +/- 3.7 pmol/oocyte/h) in comparison with water
      injected oocytes. The uptake of TEA in mRNA-injected oocytes was significantly
      inhibited by 5 mM of unlabeled TEA, cimetidine, and N1-methylnicotinamide. These
      data suggest that polyspecific organic cation transport activity can be
      successfully expressed in Xenopus laevis oocytes injected with mRNA isolated from
      human kidney.

PMID- 9188061
TI  - Nonlinear pharmacokinetics of 5-fluorouracil in rats.
AB  - The effects of dose on the pharmacokinetics of 5-fluorouracil (5-FU) were
      investigated following intravenous administration of 5-FU at 10, 50, and 100
      mg/kg to adult male Sprague-Dawley rats. Six rats were studied at each dose
      level. The dose-normalized area under the curve (AUC) was significantly higher
      after administration of 100 mg/kg (1.14 +/- 0.55 mg.h/L/mg; mean +/- SD) than
      after 50 mg/kg (0.50 +/- 0.18 mg.h/L/mg) or 10 mg/kg (0.43 +/- 0.11 mg.h/L/mg),
      indicating nonlinear elimination of 5-FU in rats. Dose- and time-average
      pharmacokinetic parameters were calculated by area/moment analysis. The systemic
      clearance of 5-FU following administration of 100 mg/kg was significantly lower
      (1.1 +/- 0.49 L/h/kg) than after 50 mg/kg (2.2 +/- 0.72 L/h/kg) or 10 mg/kg (2.4
      +/- 0.67 L/h/kg). There was no significant difference in renal clearance values
      between the three doses (0.47 +/- 0.26 L/h/kg). However, nonrenal clearance was
      significantly lower after the 100-mg/kg dose (0.77 +/- 0.2 L/h/kg) than after the
      50-mg/kg (1.65 +/- 0.49 L/h/kg) and 10-mg/kg (1.87 +/- 0.75 L/h/kg) doses. There
      was no significant difference between the steady-state volume of distribution
      values (0.91 +/- 0.36 L/kg) at the three doses. The lower nonrenal clearance
      following the 100-mg/kg dose compared with that after the lower doses of 5-FU
      suggested nonlinear metabolism of 5-FU in rats. A two-compartment pharmacokinetic
      model with parallel first-order (renal excretion) and Michaelis-Menten
      elimination from the central compartment was simultaneously fit to mean plasma 5
      FU concentration versus time data for the three doses. The maximum volume (Vmax)
      and Michaelis constant (Km) values averaged (mean +/- SE) 8.3 +/- 2.3 mg/h and
      31.6 +/- 11.9 mg/L, respectively. The information obtained in this study will be
      valuable for the evaluation of prodrugs of 5-FU that are designed to reduce
      toxicities and to improve oral bioavailability of the anticancer agent.

PMID- 9188062
TI  - Effects of skin metabolism on percutaneous penetration of lipophilic drugs.
AB  - Effects of skin metabolism on percutaneous penetration of drugs with high
      lipophilicity were studied in vitro using rat skin pretreated with and without an
      esterase inhibitor, diisopropyl phosphorofluoridate [also known as diisopropyl
      fluorophosphate (DFP)]. Without DFP, about 96% of the total penetrated amount
      appeared as metabolized p-hydroxybenzoic acid in the receptor fluid after
      application of butylparaben, whereas about 30% penetrated as intact form after
      application of propylparaben. On the other hand, metabolized p-hydroxybenzoic
      acid was not defected in the receptor fluid under pretreatment with DFP. DFP
      significantly decreased (p < 0.05) the total amount that penetrated after
      application of butylparaben, but it did not significantly affect that of
      propylparaben. The results indicate that skin metabolism directly affects total
      amount that penetrated in the case of highly lipophilic drugs, and it was found
      that the higher metabolic rate to hydrophilic drugs is, the greater the amount
      that penetrated the skin would be. Thus, when optimal prodrugs are designed for
      the purpose of enhancing percutaneous penetration, we propose that the
      bioconversion rate to parent drugs as well as the lipophilicity of prodrugs
      becomes an important consideration.

PMID- 9188063
TI  - Characterization of complexes of oligonucleotides with polyamidoamine starburst
      dendrimers and effects on intracellular delivery.
AB  - This study evaluates polyamidoamine PAMAM "starburst" dendrimers (generation 3,
      Mr 6909) as a potential delivery vehicle for oligonucleotides. Complexes between
      dendrimer and phosphorothioate oligonucleotides were observed by agarose gel
      electrophoresis and were positive, negative, or neutral in charge depending on
      stoichiometry. Complexes were stable in 50% serum to variations in pH (3, 5, and
      10) and ionic strength (0-500 mM). Ultrafiltration and gel filtration
      characterization indicated that the dendrimer:oligonucleotide complexes were
      primarily < 100 kD, although some larger complexes were formed at oligonucleotide
      excess. Use of dendrimers resulted in a 50-fold enhancement in cell uptake of
      oligonucleotide as determined by flow cytometry, and enhanced cytosolic and
      nuclear availability, as shown by confocal microscopy. These data support the
      further evaluation of dendrimers for oligonucleotide delivery in cell culture and
      in vivo.

PMID- 9188064
TI  - Computational sequence analysis of the tissue inhibitor of metalloproteinase
      family.
AB  - The tissue inhibitor of metalloproteinase (TIMP) family regulates extracellular
      matrix turnover and tissue remodeling by forming tight-binding inhibitory
      complexes with matrix metalloproteinases (MMPs). MMPs and TIMPs have been
      implicated in many normal and pathological processes, such as morphogenesis,
      development, angiogenesis, and cancer metastasis. This minireview provides
      information that would aid in classification of the TIMP family and in
      understanding the similarities and differences among TIMP members according to
      the physical data, primary structure, and homology values. Calculations of
      molecular weight, isoelectric point values, and molar extinction coefficients are
      reported. This study also compares sequence similarities and differences among
      the TIMP members through calculations of homology within their individual loop
      regions and the mature region of the molecule. Lastly, this report examines
      structure-function relationships of TIMPs. Thorough knowledge of TIMP primary and
      tertiary structure would facilitate the uncovering of the molecular mechanisms
      underlying metalloproteinase, inhibitory activities and biological functions of
      TIMPs.

PMID- 9188065
TI  - Detection and characterization of a protein isoaspartyl methyltransferase which
      becomes trapped in the extracellular space during blood vessel injury.
AB  - Injury to rat blood vessels in vivo was found to release intracellular pools of
      protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) into the
      extracellular milieu, where it becomes trapped. This trapped cohort of PIMT is
      able to utilize radiolabeled S-adenosyl-L-methionine (AdoMet) introduced into the
      circulation to methylate blood vessel proteins containing altered aspartyl
      residues. As further shown in this study, methylated substrates are detected only
      at the specific site of injury. In vitro studies more fully characterized this
      endogenous PIMT activity in thoracic aorta and inferior vena cava. Methylation
      kinetics, immunoblotting, and the lability of methylated substrates at mild
      alkaline pH were used to demonstrate that both types of blood vessel contain an
      endogenous protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT). At
      least 50% of the PIMT activity is resistant to nonionic detergent extraction,
      suggesting that the enzyme activity becomes trapped within or behind the
      extracellular matrix (ECM). Quantities of lactate dehydrogenase (LDH), another
      soluble enzyme of presumed intracellular origin, were found to be similarly
      trapped in the extracellular space of blood vessels.

PMID- 9188066
TI  - Injury-induced enzymatic methylation of aging collagen in the extracellular
      matrix of blood vessels.
AB  - As a result of blood vessel injury, protein D-aspartyl/L-isoaspartyl carboxyl
      methyltransferase (PIMT), a normally intracellular enzyme, becomes trapped within
      the meshwork of the vascular extracellular matrix where it can methylate
      substrate proteins. In this investigation we examined the distribution of such
      altered aspartyl-containing substrate proteins in the vascular wall. Nearly 90%
      of all the altered aspartyl residues were inaccessible to intracellular PIMT.
      Proteins of the extracellular matrix were found to be the major repository of
      altered aspartyl-containing polypeptides in the blood vessel wall, accounting for
      approximately 70% of the total amount. Proteolytic cleavage of extracellular
      matrix proteins with cyanogen bromide (CNBr) revealed that collagens account for
      most of the altered aspartyl-containing proteins of the ECM. As a consequence of
      blood vessel injury, both type I and type III collagen along with other proteins
      were found to become methylated by injury-released PIMT. It is estimated that 1
      cm of vein contains on the order of 5 x 10(14) altered aspartyl residues
      involving between 1% and 5% of the total extracellular protein.

PMID- 9188067
TI  - alpha-Crystallin acting as a molecular chaperonin against photodamage by UV
      irradiation.
AB  - alpha-Crystallin, a major protein of the eye lens, is known to have chaperone
      activity in preventing heat-induced aggregation of enzymes and other crystallins.
      In this study, we investigate the ability of alpha-crystallin to inhibit UV-light
      induced aggregation of other lens proteins and the effect of exposure of alpha
      crystallin to UV irradiation on its chaperone activity. The chaperone activities
      of alpha-crystallin preincubated at different temperatures were found to be
      different and could be correlated with its change in quaternary structure as
      determined by the fluorescence probe ANS (8-anilo-1-naphthalene sulfonate). alpha
      Crystallin can inhibit the aggregation of gamma-crystallin from UV irradiation at
      room temperature, and the preheated alpha-crystallins provide more protection
      than the native one. Upon irradiation by UV light, alpha-crystallin gradually
      lost its ability to protect beta-crystallin against thermal aggregation. The loss
      of the chaperone efficacy of alpha-crystallin to protect other lens proteins may
      shed light on human cataract formation induced by long-term exposure to UV
      irradiation.

PMID- 9188068
TI  - The mechanism of 2,2,2-trichloroacetic acid-induced protein precipitation.
AB  - The mechanism of 2,2,2-trichloroacetic acid (TCA)-induced precipitation of
      proteins is studied. The TCA-induced protein precipitation curves are observed to
      be U-shaped. It is bound that the protein-precipitate-inducing effects of TCA are
      due to the three chloro groups in the molecule. Using cardiotoxin III (CTX III)
      isolated from the Taiwan cobra (Naja naja atra), as a model protein, we attempt
      to understand the molecular basis for the TCA-induced effects. Employing circular
      dichroism, proton-deuterium exchange in conjunction with conventional 2D NMR
      techniques, and 1-anilino naphthalene-8-sulfonate-binding experiments, we
      demonstrate that CTX III is in a partially structured state similar to the 'A
      state' in 3% w/v TCA. It is postulated that the formation of this 'sticky'
      partial structured 'A state' in the TCA-induced unfolding pathway is responsible
      for the acid-induced protein precipitation.

PMID- 9188069
TI  - Sequence characterization of gamma-crystallins from lip shark (Chiloscyllium
      colax): existence of two cDNAs encoding gamma-crystallins of mammalian and
      teleostean classes.
AB  - gamma-Crystallin is a common lens protein of most vertebrate eye lenses and the
      major protein component in lenses of fishes and in many mammalian species during
      embryonic and neonatal stages. To facilitate the structural characterization of
      gamma-crystallin possessing extensive charge heterogeneity, a cDNA mixture was
      constructed from the poly(A)+ mRNA isolated from shark eye lenses, and
      amplification by polymerase chain reaction (PCR) was carried out to obtain cDNAs
      encoding multiple shark gamma-crystallins. Sequencing analysis of multiple
      positive clones containing PCR-amplified inserts revealed the presence of a
      multiplicity of isoforms in the gamma-crystallin class of this cartilaginous
      fish. It was of interest to find that two shark cDNA sequences coexist, one
      encoding gamma-crystallin (gamma M1) of high methionine content (15.5%) and the
      other encoding one (gamma M2) of low methionine content (5.1%), each
      corresponding to the major teleostean and mammalian gamma-crystallins,
      respectively. Comparison of protein sequences encoded by these two shark cDNAs
      with published sequences of gamma-crystallins from mouse, bovine, human, frog,
      and carp lenses indicated that there is about 61-80% sequence homology between
      different species of the piscine class, whereas only 47-66% is found between
      mammals and shark. A phylogenetic tree constructed on the basis of sequence
      divergence among various gamma-crystallin cDNAs revealed the close relatedness
      between shark gamma M2-crystallin and mammalian gamma-crystallins and that
      between shark gamma M1 and teleostean gamma-crystallins. The results pointed to
      the fact that ancestral precursors of gamma-crystallins were present in the sharp
      lens long before the appearance of modern-day mammalian and teleostean gamma
      crystallins.

PMID- 9188071
TI  - Self-focused and somatic attention in patients with tinnitus.
AB  - Self-focused and somatic attention were examined in a sample of 51 patients with
      tinnitus using the Self-Focus Sentence Completion Test, Private Self
      Consciousness Subscale of the Self-Consciousness Scale, Modified Somatic
      Perception Questionnaire, and the Somatization Subscale of the Symptoms Checklist
      90-Revised. Two subgroups of patients emerged following a cluster analysis of the
      attentional tasks. One group scored lower on both self-attention and somatic
      attention measures ("low self-attenders"), whereas a second group was more
      internally directed and scored higher on the attention measures ("high self
      attenders"). Between-group comparisons showed that the high self-attenders were,
      on average, more depressed, had greater emotional distress due to tinnitus, and
      had greater perceived tinnitus handicap. In contrast, no differences were
      observed for pitch and loudness measures using either psychophysical or rating
      scale techniques. Results of this investigation support the belief that
      attentional mechanisms play an important role in patients' perception of tinnitus
      and should be considered when planning management strategies.

PMID- 9188070
TI  - Physical and epitope analysis of a recombinant human T-cell receptor V alpha/V
      beta construct support the similarity to immunoglobulin.
AB  - The genetic organization and protein structure of T-cell receptors (TCR) and
      immunoglobulins (Ig) are remarkably similar. Through recombinant, physical, and
      peptide-based immunological studies we demonstrated that rabbit antisera
      generated against a recombinant single-chain TCR (scTCR) react with defined
      peptide epitopes of their constituent TCR alpha and beta chains. These antisera
      cross-react with the lambda light-chain Mcg as well as with peptides duplicating
      its covalent structure. Conversely, rabbit antisera generated to human lambda
      light chains cross-reacted with the recombinant scTCR. Rabbit anti-lambda
      antibodies purified on an scTCR affinity column bound to T-cell lines and to T
      and B lymphocytes from peripheral blood. Circular dichroism analysis demonstrated
      plots characteristic of beta-sheets for both Mcg and recombinant scTCR. Antisera
      directed against TCR alpha-chain synthetic peptides reacted with scTCR, Mcg
      lambda light-chain protein, synthetic peptides from regions of sequence homology
      in beta-chains, and Mcg. Based upon this homology and the serological cross
      reactions which reflect conformational determinants, we suggest that the V
      alpha/V beta antigen-binding domain of this particular monoclonal scTCR construct
      is substantially similar to the conformational structure of lambda light chains.

PMID- 9188072
TI  - Age-related changes in monosyllabic word recognition performance when audibility
      is held constant.
AB  - Monosyllabic word recognition was studied in 140 subjects between the ages of 20
      and 90 years. The subjects were tested under a condition of fixed audibility that
      was achieved by presenting bandpass-filtered Northwestern University Auditory
      Test No. 6 (NU-6) word lists at a constant signal-to-noise ratio and limiting
      threshold losses at the speech frequencies to 25 dB HL. The results indicated the
      following: (1) Performance did not vary appreciably with age, except among
      subjects over 70 years. Subjects from 70 to 80 years produced modestly reduced
      scores (significantly below only the 30-year-old group). Those over 80 years
      produced significantly lower scores (than all other groups). (2) There were no
      significant differences in learning or test-retest reliability associated with
      age. (3) The performance of the oldest subjects could not be explained by
      differences in speech audibility. Based on these results, a strategy is proposed
      for correcting predicted word recognition scores for the effects of age.

PMID- 9188073
TI  - Performance norms for the VA compact disc versions of CID W-22 (Hirsh) and PB-50
      (Rush Hughes) word lists.
AB  - The purpose of this study was to establish normative articulation functions for
      the Hirsh recordings of the CID W-22 word lists and te Rush Hughes recordings of
      the PB-50 word lists as recorded on the VA compact disc. Twenty-four young adults
      with normal hearing listened to both sets of materials presented in quiet at 12
      levels (0-56 dB HL). Presentation levels on average needed to be 10 dB higher for
      the PB-50 word lists to obtain word recognition performance scores equal to those
      for the W-22s. Maximum word recognition scores of 95 to 100 percent were obtained
      for the W-22s at lower presentation levels (> 40 dB HL), compared to 80 to 90
      percent for the PB-50s at the maximum presentation level (56 dB HL). Mean slopes
      for the W-22 and PB-50 functions were 4.1 percent/dB and 1.9 percent/dB,
      respectively. Test-retest reliability was judged to be clinically appropriate for
      both sets of materials. Item analyses revealed a substantially skewed
      distribution toward easy items for the W-22 word lists compared to a more
      balanced distribution of item difficulty for the PB-50 lists. List equivalency
      was also judged to be clinically appropriate for the PB-50 word lists.

PMID- 9188074
TI  - Conventional and maximum length sequences middle latency response in patients
      with central nervous system lesions.
AB  - Conventional and maximum length sequence (MLS) middle latency response (MLR)
      procedures were compared across several parameters for control patients and
      patients with central nervous system lesions. There were similar findings for
      both populations and both types of MLR for the absolute latencies of Na and Pa
      waves. Middle latency waves were absent more often in the neurologic than control
      subjects for both the conventional and MLS-MLR procedures. Overall, more MLR
      waves were present for the MLS technique than for the conventional MLR technique.
      Differences in wave amplitude were significant for several recording sites when
      comparing neurologic with control groups, but findings were similar for wave
      amplitude when comparing the two types of MLR procedures for the neurologic
      population. Based on these findings, no clear diagnostic advantage was shown for
      using the MLS-MLR technique. These findings are further discussed.

PMID- 9188075
TI  - Use of acoustic reflectometry in the detection of middle ear effusion.
AB  - The purpose of the present investigation was to compare the performance of the
      acoustic otoscope/DPU-411 printer and acoustic immittance with otoscopic
      examinations by a physician for the detection of middle ear effusion (MEE). Three
      hundred and two patients (11 months to 69 years) were evaluated with the acoustic
      otoscope, acoustic immittance, and otoscopic examinations. The patients were
      divided into two age groups for data analysis: 1 to 12 years (children) and 13 to
      69 years (adults). Reflectivity and angle data were evaluated at different cut
      off points and receiver operating characteristics (ROC) curves were determined.
      The variables were analyzed in different combinations for each study group.
      Sensitivity and specificity were poorest for the acoustic otoscope in children.
      Furthermore, acoustic immittance data compared more favorably with otoscopy than
      did the acoustic otoscope for all ages.

PMID- 9188076
TI  - Monaural/binaural preferences: effect of hearing aid circuit on speech
      intelligibility and sound quality.
AB  - This investigation compared monaural and binaural hearing aid preferences of 15
      adults with mild-to-moderately-severe bilaterally symmetrical sensorineural
      hearing losses. Subjects listened to connected discourse in quiet and background
      noise at 70 and 80 dB SPL with K-Amp, linear Class D, linear output limiting
      compression (OLC), Manhattan II, and linear asymmetrical peak clipping circuits
      (APC). In Experiment 1, subjects made judgments of sound quality and speech
      intelligibility in a modified paired-comparison paradigm during which they
      compared the monaural and binaural fittings of each circuit. In Experiment 2,
      subjects engaged in subjective ratings on a scale of 0 to 10. Subjects benefitted
      from improved sound quality and speech intelligibility in high-noise conditions
      when fit with binaural K-Amp, linear Class D, linear OLC, and Manhattan II
      circuits. Monaural listening was preferred with the APC circuit. Results indicate
      that improved sound quality and speech intelligibility may be obtained with
      binaural fittings of circuits that include high fidelity, low distortion, or
      increased head-room.

PMID- 9188077
TI  - Communication Scale for Older Adults (CSOA).
AB  - The communication Self-Assessment Scales for Older Adults (CSOA) are comprised of
      a 41-item Communication Strategies scale and a 31-item Communication Attitudes
      scale. Three-point and 5-point response formats are available. The scales were
      standardized on a population of 135 independent-living adults with hearing loss,
      ranging in age from 60 to 88 years. Item analysis, internal consistency
      reliability, test-retest reliability, normative data, and 95 percent confidence
      intervals are presented. A sample case illustrates how the scales can be used to
      evaluate the communication strategies and attitudes of an individual client. In
      addition, data are presented to show changes in the use of communication
      strategies and attitudes of a group of clients 3 months and 9 months after
      completion of aural rehabilitation programs.

PMID- 9188078
TI  - Multifrequency tympanometry and evoked otoacoustic emissions in neonates during
      the first 24 hours of life.
AB  - Multifrequency, complex-component tympanograms and transient evoked otoacoustic
      emissions (EOAEs) were recorded in 55 neonates less than 24 hours of age. The
      purpose of the investigation was to determine the normal middle ear immittance
      characteristics of neonates less than 24 hours old (the approximate discharge age
      of well-babies) and to assess whether an association exists between transient
      EOAE response and middle ear status in neonatal ears. The tympanometric patterns
      recorded in the 55 neonates were, in general, not typical of those observed in
      older children and adults. Complex patterns were recorded at low probe
      frequencies indicating differences in the contribution of mass, stiffness, and
      resistance elements to admittance in the neonatal middle ear. Results from EOAE
      screening indicated a pass rate or partial pass rate of 82 percent. Although no
      clear association emerged between admittance characteristics and EOAE results,
      some interesting tendencies were noted.

PMID- 9188079
TI  - Distribution of enkephalin-like immunoreactivity in the cat digestive tract.
AB  - Immunohistochemical investigations were carried out to determine the pattern of
      distribution of methionine- and leucine-enkephalin-like materials in the cat
      pylorus, duodenum, ileum and proximal and distal colon. The present results
      indicate that leucine-enkephalin-like materials are less densely distributed than
      methionine-enkephalin-like materials, but that the two patterns of distribution
      show some similarities. Considerable regional differences exist however in the
      distribution of these enkephalin-like materials in the muscular layers. In the
      duodenum, ileum and proximal colon, the immunoreactivity was mainly confined to
      the myenteric plexus and the circular muscle layer, where it was present in nerve
      cell bodies and in numerous fibres. In the longitudinal muscle and submucous
      layers, a few immunoreactive fibres were observed which sometimes surrounded
      blood vessels. In the pylorus and the distal colon, however, numerous
      immunoreactive fibres were observed in the longitudinal and circular muscle
      layers; the immunoreactivity was detected in the cell bodies of numerous
      myenteric plexus neurons but those of only a few submucous plexus neurons. In
      addition, the pylorus tissues contained immunoreactive plexi which were localized
      either within the longitudinal muscle or between the serosa and the longitudinal
      muscle layer. These plexi were connected to the myenteric plexus by
      immunoreactive nerve strands. In all the small intestinal segments studied,
      numerous immunoreactive varicosities were present in the deep muscular plexus, in
      the inner part of the circular muscle layer. Our results suggest that in cats,
      the nervous control of external muscular layers mediated by enkephalins shows
      regional differences. In the pylorus and the distal colon, it involves both the
      longitudinal and circular muscle layers, whereas in other intestinal segments,
      only the circular muscle layer is involved.

PMID- 9188080
TI  - Identification of the cholinergic neurons in guinea-pig sphincter of Oddi
      ganglia.
AB  - The muscular tone of the sphincter of Oddi (SO) can be up- or down-regulated by
      neurons that lie within ganglia in the wall of the tissue. Previous studies have
      demonstrated that neurons in the ganglia of the guinea-pig SO can be classified
      into two major populations, one of which expresses tachykinins and enkephalin and
      another which expresses nitric oxide synthase. Although results of previous
      pharmacological studies indicate that acetylcholine is released in the SO, the
      neurons that express this neurotransmitter have not previously been identified.
      This study was conducted to establish which neurons in the ganglia of the guinea
      pig SO are cholinergic by examining the distribution of choline acetyltransferase
      (ChAT) immunoreactivity, since the enzyme, ChAT is necessary for acetylcholine
      synthesis. Choline acetyltransferase immunoreactivity was intense and widespread
      in the ganglionated plexus of the SO. ChAT-immunoreactive nerve fibers were
      present in ganglia, interganglionic fiber bundles and in the circular muscle
      layer. Neurons that were immunoreactive for ChAT comprised about 69% of the
      population and most of these neurons were also tachykinin-immunoreactive. Co
      expression of ChAT and nitric oxide synthase was not observed in nerve cell
      bodies or nerve fibers. Data from this study support the concept that SO ganglia
      are largely made up of two populations of neurons, one excitatory and the other
      inhibitory, on the basis of their chemical coding. The excitatory neurons are
      cholinergic and co-express tachykinin and opiate peptides and the inhibitory
      neurons are ChAT-negative and express nitric oxide synthase.

PMID- 9188081
TI  - Evidence for sexual differences in the preoptic area regulation of blood glucose
      in rats.
AB  - The effect of noradrenaline (NA) injection (20 or 40 nmol) into the preoptic area
      (POA) on plasma glucose and insulin was studied in male and female rats. The rats
      were implanted with chronic jugular catheters for blood sampling and unilateral
      intracerebral cannulas placed just above the POA. Blood samples were taken before
      and at 5, 10, 15, 30 and 60 min after NA injection. As early as 5 min after NA
      injection, plasma glucose levels rose rapidly in both male and female rats,
      reaching a peak at 15 min poststimulus. NA injection into the POA caused a dose
      dependent hyperglycemic response in both male and female rats, although the
      response was more intense and longer lasting in females than in males. However,
      NA injection into the POA induced an increase in plasma insulin concentration in
      male but not in female rats. In addition, the increase in plasma glucose induced
      by 40 nmol NA injection in males preceded that of insulin. Plasma levels of
      glucose after POA injection of NA were already significantly elevated (p < 0.01)
      within the first experimental interval (5 min), whereas a plasma insulin increase
      were first detected 15 min post injection. We conclude that, when administered
      locally into the POA, NA can activate the sympathetic outflow expressed by a
      neurally mediated hyperglycemia which is more intense in females than in males.
      These data demonstrate that the POA has a sexually differentiated function in the
      regulation of glycemia.

PMID- 9188082
TI  - The diastolic decay constant in spontaneously hypertensive rats versus WKY rats
      as an indicator for vasomotor control.
AB  - This research uses the diastolic decay constant (tau) to investigate the short
      term mechanism responsible for vasomotor control, mainly the alpha-sympathetic
      control system. Previous studies have shown that vasomotor control is altered in
      spontaneously hypertensive rats (SHR) preceding the phase of overt hypertension.
      The diastolic decay, according to the two element Windkessel model, displays an
      exponential shape with a decay constant, tau, depending on both the vascular
      resistance and the compliance. In our experiments, we used tau to characterize
      vasomotor activity and its control in the normotensive rats as well as in the
      spontaneously hypertensive rats (SHR) prone to hypertension. The beat to beat
      value of tau was evaluated from a continuous arterial blood pressure (ABP)
      signal, measured in the tail artery of the conscious, unrestrained rat. Four
      months old prehypertensive SHR were compared to their age matched normotensive
      controls (WKY). To study vasomotor regulation, we computed gains and delay times
      by investigating the compensatory response in tau to changes in mean ABP (MBP).
      These parameters are expected in the short term to be neurally controlled by the
      sympathetic system, mainly alpha-sympathetic. Our set of experiments consisted of
      changing MBP by performing successive injections in bolus of increasing doses of
      the vasoconstrictor angiotensin II. This procedure was repeated under double
      cardiac autonomic blockade of the vagal and beta 1 = sympathetic limbs. Our
      results show that, under baseline conditions, the absolute gain and delay times
      of tau are reduced in SHR compared to WKY. Double cardiac blockade decreases the
      absolute gain in both strains, while abolishing the baseline strain differences.
      These results reinforce our assumption that, in SHR, the alpha-sympathetic system
      is in a basic state of excitation even prior to the onset of overt hypertension
      and therefore reacting with reduced sensitivity (lower gain) to changes in MBP.

PMID- 9188083
TI  - Autonomic response to change of posture among normal and mild-hypertensive
      adults: investigation by time-dependent spectral analysis.
AB  - In this study, we applied the time-dependent spectral analysis approach (SDA) to
      investigate the autonomic changes occurring during a transition from supine to
      standing position (CP), in normal and unmedicated mild hypertensive subjects. The
      SDA method enables an accurate follow-up of the instantaneous changes in
      autonomic activity, even during the unsteady phase of the transition, where
      sudden changes in heart rate (HR) and arterial blood pressure (ABP) are observed.
      We were able to quantify the vagal withdrawal (reflected in the high frequency
      component of the time-dependent spectrum of HR fluctuations) in the immediate
      response to CP and the more slowly following sympathetic increase (reflected in
      the low frequency component of ABP). This general pattern was observed in both
      groups. In addition, our results identified an altered sympathetic response to CP
      in mild-hypertensives, as compared to normal adults. Their basal sympathetic
      activity is enhanced (higher mean HR and increased low frequency fluctuations in
      ABP) and their response to CP is reduced, as reflected only in the LF content of
      ABP fluctuations, relative to normals. No difference was observed in HR
      fluctuations, showing that there is no parasympathetically mediated alteration of
      the baroreflex control of HR in mild-hypertension.

PMID- 9188084
TI  - Section of the vagal celiac branch in man reduces glucagon-stimulated insulin
      release.
AB  - The purpose of this study was to determine whether section of the celiac branch
      of the vagus nerve in man affects the insulin response to intravenous glucagon
      injection. Patients who received a subtotal gastrectomy with lymph node
      dissection for gastric carcinoma were divided into two groups: the celiac
      preserved group (n = 16) and the celiac-sectioned group (n = 13). The hepatic
      branches of the vagus were preserved in both groups. The glucagon test was
      performed twice in each patient during the operation; before and after
      manipulation of the celiac branch. Blood samples were collected just before and 6
      min after the injection. No difference in the mean increases in blood glucose,
      insulin and C-peptide levels were seen between the two groups before the nerve
      manipulation. In the celiac-preserved group, the glucagon stimulated glucose
      related C-peptide ratio (x 10(-3) was 0.5 +/- 0.7 before the nerve manipulation
      and 3.5 +/- 3.0 after it, a significant difference (p < 0.01). In the celiac
      sectioned group, this increase was not observed, the ratio was 0.7 +/- 0.6 before
      the nerve manipulation and 0.8 +/- 3.4 after. These results indicate that the
      vagal celiac branch in man may also be involved in the control of pancreatic
      insulin release.

PMID- 9188085
TI  - 3.5% hypertonic saline produces sympathetic activation in hemorrhaged rabbits.
AB  - The neural mechanisms for pressor effects after hypertonic saline infusion are
      still unclear. Using direct measurement of the renal sympathetic nerve activity
      (RNA), we tested the hypothesis that the autonomic nervous system is involved in
      an acute blood pressure elevation produced by hypertonic saline (HTS) in
      anesthetized rabbits subjected to hemorrhage. Twenty urethane-anesthetized
      rabbits were ventilated mechanically after a tracheostomy and paralyzed with
      gallamine triethiodide. Heart rate (HR), mean blood pressure (MBP) and central
      venous pressure (CVP) were measured simultaneously with RNA. The animals were
      divided into the following four groups: (1) animals with intact baroreceptors
      that received HTS (intact HTS group, N = 5); (2) those with intact baroreceptors
      that received normal saline (intact NS group, N = 5); (3) those that underwent
      selective cervical vagotomy (vagotomy group, N = 5); (4) those with sino-aortic
      denervation (SAD group, N = 5). The last two groups were given HTS only. After
      inducing hemorrhagic hypotension to 40 mmHg over 10 min, 3.5% HTS at half the
      volume of shed blood was infused over approximately 120 s. In the intact HTS
      group, sympathetic activation, associated with tachycardia and pressor effects,
      developed. This enhancement of RNA was followed by a return to the pre-infusion
      level, but the increased blood pressure and tachycardia lasted until the end of
      the experiment. These levels of MBP and HR were significantly higher than those
      of the intact NS group. In the vagotomized animals, HTS resuscitation also
      increased RNA and systemic blood pressure. In contrast, in the SAD group, neither
      sympathetic activation nor an early phase increase in systemic blood pressure
      occurred. These results indicate that in hemorrhaged rabbits, 3.5% HTS produces
      sympathetic activation along with an acute pressor effect and that this is likely
      to be mediated through the sino-aortic nerves, possibly the peripheral
      chemoreceptors, but not through the vagal nerves.

PMID- 9188086
TI  - Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous
      activity in healthy human subjects.
AB  - Studies using internal jugular vein blood sampling in human subjects have
      demonstrated the release of noradrenaline from the brain and have provided a link
      between central nervous system noradrenergic neuronal activity and renal, cardiac
      and total body sympathetic activity. The aim of this study was to further
      categorise the dependence of regional sympathetic nervous function on central
      nervous system noradrenergic neuronal processes by combining measures of internal
      jugular venous noradrenaline spillover, as an indicator of brain noradrenaline
      release, and cerebral blood flow scans with measures of the overall integrated
      neuronal firing rate for the body as a whole, the spillover of noradrenaline into
      the coronary sinus and with measurements of resting muscle sympathetic nerve
      activity. Positive veno-arterial plasma noradrenaline gradients were found across
      the brain, with the plasma concentration being 17 +/- 3% (p < 0.01) greater in
      the internal jugular vein. Linear regression analysis revealed a significant
      relationship between the degree of muscle sympathetic nerve activity and the
      spillover of noradrenaline from subcortical brain regions (y = 0.1 x + 16.0; r =
      0.81, p < 0.02). The rate of spillover of noradrenaline for the body as a whole
      also bore a significant association with the rate of subcortical noradrenaline
      spillover (y = 0.01x + 2.33; r = 0.71, p < 0.05). Cortical noradrenaline
      spillover was not related to any of the sympathetic nervous system parameters
      measured in this study. The demonstration of a direct relationship between the
      rate of peroneal nerve firing and the spillover of noradrenaline from subcortical
      brain regions provides further support for the concept of central nervous system
      noradrenergic cell groups behaving in a sympathoexcitatory role.

PMID- 9188087
TI  - Detection of the phosphorylcholine epitope in streptococci, Haemophilus and
      pathogenic Neisseriae by immunoblotting.
AB  - The phosphorylcholine (PC) determinant in Streptococcus pneumoniae is known to be
      linked to the cell wall polysaccharides (C-Ps) and to the lipoteichoic acid (LTA)
      (Forssman antigen) of the plasma membrane. Western blotting with two PC specific
      murine monoclonal antibodies (MAbs) designated 145,F-2 (IgM) and 147,A-1 (IgA)
      showed a similar ladder-like pattern for all examined strains of S. pneumoniae
      and Streptococcus mitis. Purified antigens run in parallel indicated that this
      ladder pattern is due to the PC of LTA. Unlike other techniques, Western blotting
      thus enables the identification of only one of the streptococcal structures
      carrying the PC epitope. Gram-negative organisms were also examined, and six of
      11 Haemophilus influenzae strains reacted with the MAbs. For this species, unlike
      the streptococci, only one fast moving band was detected. Analyses by thin-layer
      chromatography (TLC) detected the PC epitope in lipopolysaccharide (LPS) fraction
      from H. influenzae. Some strains of the Neisseriaceae family were also positive
      by Western blotting, but TLC and immunostaining did not detect the PC determinant
      in LPS.

PMID- 9188088
TI  - Localization of the in vivo expression of P and F1 fimbriae in chickens
      experimentally inoculated with pathogenic Escherichia coli.
AB  - Escherichia coli causing septicemia in poultry often possess F1 (type 1) and/or P
      fimbriae which may be involved in bacterial colonization and infection. To
      investigate the expression of these fimbriae in vivo, two pathogenic E. coli
      strains with different fimbrial profiles, TK3 (fim+/pap+) and MT78 (fim+/pap-),
      were administered to 2-week-old chickens by either the intratracheal or caudal
      thoracic air sac inoculation route. Antibodies specific for native F1 fimbriae
      were detected by ELISA and immunodot in the serum of chickens inoculated with
      either strain MT78 or strain TK3, irrespective of the route of inoculation.
      Antibodies specific for P fimbriae of serotype F11 were detected by ELISA and
      immunoblotting in the serum of chickens inoculated by either route with strain
      TK3. F1, but not P fimbriae, were expressed by bacteria colonizing the trachea of
      chickens inoculated by the air sac route with strain MT78 or TK3, as demonstrated
      by examination of frozen tissue sections using immunofluorescence. F1 fimbriae
      were also expressed by bacteria colonizing the air sacs and lungs, but not by
      bacteria in the blood or other internal organs, of chickens inoculated with
      either strain. P fimbriae were expressed by bacteria colonizing the air sacs,
      lungs, kidney, blood, and pericardial fluid, but not by bacteria colonizing the
      trachea, of chickens inoculated with strain TK3. Fimbriae-like structures were
      observed by electron microscopy on bacteria adhering to the epithelial cells of
      the air sacs of chickens inoculated with strain TK3. These results demonstrate
      that both strains MT78 and TK3 undergo in vivo phase variation with respect to
      their fimbrial profiles and site of bacterial colonization in different organs of
      infected chickens and suggest that F1 fimbriae are important for initial
      bacterial colonization of the upper respiratory tract whereas P fimbriae are
      important for later stages of the infection.

PMID- 9188089
TI  - Characterization of bacteriophages from tox-containing, non-toxigenic isolates of
      Corynebacterium diphtheriae.
AB  - Non-toxigenic strains of Corynebacterium diphtheriae continue to cause disease
      within immunized populations. A subset of these corynebacteria carry the
      diphtheria toxin gene but in a cryptic form. To determine whether such strains
      might contribute to the re-emergence of functional toxin genes, the phages and
      tox mutations within three clone types were examined. tox-containing, beta
      related phages were isolated from two of the strain types. The third isolate
      appeared to harbour a defective prophage. One of the tox- phages encoded
      truncated, yet enzymatically-active, forms of diphtheria toxin, suggesting that
      it had sustained a point mutation within the latter half of its toxin gene. In
      contrast, the other mutant phage did not elicit the production of either a cross
      reacting material or an ADP-ribosylating activity. Complementation tests
      employing a series of double lysogens confirmed that the mutations responsible
      for the non-toxigenic phenotype of all of the phages were cis dominant. Given
      these findings, it is reasonable to hypothesize that tox+ genes can arise within
      human populations by either homologous recombination between two distinct tox-
      phages or spontaneous reversion within a single mutant allele.

PMID- 9188090
TI  - Bacterial phenotypes mediated by mviA and their relationship to the mouse
      virulence of Salmonella typhimurium.
AB  - The focus of this study was the phenotypic characterization of Salmonella
      typhimurium mutants lacking the function of the response regulator mviA. The
      inactivation of mviA+ (mviA::kan) is shown to induce a significant change in the
      growth of most virulent strains, as reflected in the size of the colonies formed
      on agar plates. The colony phenotype observed in these strains has been
      designated as the small colony morphology (Scm+) phenotype. Mutants exhibiting
      the Scm+ phenotype are shown to be significantly attenuated for virulence in
      susceptible (ItyB) mice. The Scm+ phenotype therefore provides an in vitro
      phenotypic marker for mviA+ activity. Further examination of Scm+ mutants has
      revealed that they lack expression of a 55 kDa periplasmic protein which is
      detected in isogenic mviA+ strains. This protein has been designated mviA+
      related protein A (MrpA) and was expressed in direct correlation with virulence
      in all S. typhimurium strains examined.

PMID- 9188091
TI  - Construction and characterization of genetically-marked bivalent anti-Shigella
      dysenteriae 1 and anti-Shigella flexneri Y live vaccine candidates.
AB  - Bivalent vaccine candidates were developed against Shigella dysenteriae 1 and
      Shigella flexneri, which are among the most frequent causative agents of
      shigellosis in developing countries. The rfp and rfb gene clusters, which code
      for S. dysenteriae serotype 1 O-antigen biosynthesis, were inserted into an
      arsenite resistance minitransposon and randomly integrated into the attenuated S.
      flexneri aroD serotype Y strain SFL124. Nine recombinant clones that efficiently
      expressed both homologous and heterologous O-antigens were obtained. Southern
      blot analysis showed that in one clone the S. dysenteriae 1 genes had integrated
      into the chromosome, whereas in all the others they had integrated into the
      virulence plasmid. All recombinant clones exhibited normal growth
      characteristics, were able to invade and survive within eukaryotic cells to the
      same extent as the parental strain, and expressed efficiently the recombinant
      lipopolysaccharide within invaded cells. Immunization of mice with two of the
      recombinant clones resulted in the production of antibodies specific for both
      homologous and heterologous O-antigens. The recombinant clones constitute
      promising vaccine candidates which can readily be distinguished from endemic
      shigellae by their non-antibiotic resistance marker.

PMID- 9188092
TI  - Phorbol 12-myristate 13-acetate down-regulates Na,K-ATPase independent of its
      protein kinase C site: decrease in basolateral cell surface area.
AB  - The effect of protein kinase C (PKC) stimulation on the pump current (Ip)
      generated by the Na,K-ATPase was measured in A6 epithelia apically permeabilized
      with amphotericin B. Phorbol 12-myristate 13-acetate (PMA) produced a decrease in
      Ip carried by sodium pumps containing the endogenous Xenopus laevis or
      transfected Bufo marinus alpha 1 subunits (approximately 30% reduction within 25
      min, maximum after 40 min) independent of the PKC phosphorylation site
      (T15A/S16A). In addition to this major effect of PMA, which was independent of
      the intracellular sodium concentration and was prevented by the PKC inhibitor
      bisindolylmaleimide GF 109203X (BIM), another BIM-resistant, PKC site-independent
      decrease was observed when the Ip was measured at low sodium concentrations
      (total reduction approximately 50% at 5 mM sodium). Using ouabain binding and
      cell surface biotinylation, stimulation of PKC was shown to reduce surface Na,K
      ATPase by 14 to 20% within 25 min. The same treatment stimulated fluid phase
      endocytosis sevenfold and decreased by 16.5% the basolateral cell surface area
      measured by transepithelial capacitance measurements. In conclusion, PKC
      stimulation produces a decrease in sodium pump function which can be attributed,
      to a large extent, to a withdrawal of sodium pumps from the basolateral cell
      surface independent of their PKC site. This reduction of the number of sodium
      pumps is parallel to a decrease in basolateral membrane area.

PMID- 9188093
TI  - Association of syntaxin 3 and vesicle-associated membrane protein (VAMP) with
      H+/K(+)-ATPase-containing tubulovesicles in gastric parietal cells.
AB  - H+/K(+)-ATPase is the proton pump in the gastric parietal cell that is
      responsible for gastric acid secretion. Stimulation of acid secretion is
      associated with a reorganization of the parietal cells resulting in the
      incorporation of H+/K(+)-ATPase from a cytoplasmic membrane pool, the
      tubulovesicle compartment, into the apical canalicular membrane. To better
      characterize the role of membrane trafficking events in the morphological and
      physiological changes associated with acid secretion from parietal cells, we have
      characterized the expression and localization of soluble N-ethylmaleimide
      sensitive factor attachment protein receptors (SNAREs) in these cells. Each of
      the six different SNARE proteins examined [syntaxins 1 through 4 of 25-kDa
      synaptosome-associated protein, and vesicle-associated membrane protein] were
      found to be expressed in parietal cells. Furthermore, two of these SNAREs,
      vesicle-associated membrane protein and syntaxin 3, were associated with H+/K(+)
      ATPase-containing tubulovesicles while the remainder were excluded from this
      compartment. The expression of syntaxin 1 and synaptosome-associated protein of
      25 kDa in parietal cells, two SNAREs previously thought to be restricted to
      neuroendocrine tissues, suggests that parietal cells may utilize membrane
      trafficking machinery that is similar to that utilized for regulated exocytosis
      in neurons. Furthermore, the localization of syntaxin 3, a putative target
      membrane SNARE, to the tubulovesicle compartment indicates that syntaxin 3 may
      have an alternative function. These observations support a role for intracellular
      membrane trafficking events in the regulated recruitment of H+/K(+)-ATPase to the
      plasma membrane after parietal cell stimulation.

PMID- 9188094
TI  - Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle
      through the Wik1-Wis1-Spc1 kinase cascade.
AB  - Spc1 in Schizosaccharomyces pombe is a member of the stress-activated protein
      kinase family, an evolutionary conserved subfamily of mitogen-activated protein
      kinases (MAPKs). Spc1 is activated by a MAPK kinase homologue, Wis1, and
      negatively regulated by Pyp1 and Pyp2 tyrosine phosphatases. Mutations in the
      spc1+ and wis1+ genes cause a G2 cell cycle delay that is exacerbated during
      stress. Herein, we describe two upstream regulators of the Wis1-Spc1 cascade.
      wik1+ (Wis1 kinase) was identified from its homology to budding yeast SSK2, which
      encodes a MAPKK kinase that regulates the HOG1 osmosensing pathway. Delta wik1
      cells are impaired in stress-induced activation of Spc1 and show a G2 cell cycle
      delay and osmosensitive growth. Moreover, overproduction of a constitutively
      active form of Wik1 induces hyperactivation of Spc1 in wis1(+)-dependent manner,
      suggesting that Wik1 regulates Spc1 through activation of Wis1. A mutation of
      mcs4+ (mitotic catastrophe suppressor) was originally isolated as a suppressor of
      the mitotic catastrophe phenotype of a cdc2-3w wee1-50 double mutant. We have
      found that mcs4- cells are defective at activation of Spc1 in response to various
      forms of stress. Epistasis analysis has placed Mcs4-upstream of Wik1 in the Spc1
      activation cascade. These results indicate that Mcs4 is part of a sensor system
      for multiple environmental signals that modulates the timing of entry into
      mitosis by regulating the Wik1-Wis1-Spc1 kinase cascade. Inactivation of the
      sensor system delays the onset of mitosis and rescues lethal premature mitosis in
      cdc2-3w wee1-50 cells.

PMID- 9188095
TI  - Modification of Cys-837 identifies an actin-binding site in the beta-propeller
      protein scruin.
AB  - In the acrosomal process of Limulus sperm, the beta-propeller protein scruin
      cross-links actin into a crystalline bundle. To confirm that scruin has the
      topology of a beta-propeller protein and to understand how scruin binds actin, we
      compared the solvent accessibility of cysteine residues in scruin and the
      acrosomal process by chemical modification with (1,5-IAEDANS). In soluble scruin,
      the two most reactive cysteines of soluble scruin are C837 and C900, whereas
      C146, C333, and C683 are moderately reactive. This pattern of reactivity is
      consistent with the topology of a typical beta-propeller protein; all of the
      reactive cysteines map to putative loops and turns whereas the unreactive
      cysteines lie within the predicted interior of the protein. The chemical
      reactivities of cysteine in the acrosomal process implicate C837 at an actin
      binding site. In contrast to soluble scruin, in the acrosomal process, C837 is
      completely unreactive while the other cysteines become less reactive. Binding
      studies of chemically modified scruin correlate the extent of modification at
      C837 with the extent of inhibition of actin binding. Furthermore, peptides
      corresponding to residues flanking C837 bind actin and narrow a possible actin
      binding region to a KQK sequence. On the basis of these studies, our results
      suggest that an actin-binding site lies in the C-terminal domain of scruin and
      involves a putative loop defined by C837.

PMID- 9188096
TI  - Modification of annexin II expression in PC12 cell lines does not affect Ca(2+)
      dependent exocytosis.
AB  - The Ca2+/phospholipid/cytoskeletal-binding protein annexin II has been proposed
      to play an important role in Ca(2+)-dependent exocytosis; however, the evidence
      for this role is inconclusive. More direct evidence obtained by manipulating
      annexin II levels in cells is still required. We have attempted to do this by
      generating stably transfected PC12 cell lines expressing proteins which elevate
      or lower functional annexin II levels and using these cell lines to investigate
      Ca(2+)-dependent exocytosis. Three cell lines were generated: one expressing an
      annexin II mutant which aggregates annexin II in at least a proportion of the
      cells, thereby removing functional protein from the cell; a mixed clonal cell
      line constitutively overexpressing human annexin II; and a clonal cell line
      capable of over-expressing annexin II in the presence of sodium butyrate. After
      digitonin permeabilization, Ca(2+)-dependent dopamine release from these cell
      lines was compared with that from control nontransfected cells, and, in addition,
      release was compared in induced to uninduced cells. There were no significant
      differences in Ca(2+)-dependent exocytosis between any of the transfected cell
      lines before or after induction and the control cells. In addition,
      nontransfected PC12 cells treated with nerve growth factor, which elevates
      annexin II levels severalfold, failed to increase Ca(2+)-dependent exocytosis
      after digitonin permeabilization, compared with control cells. We conclude that
      annexin II is not an important regulator of Ca(2+)-dependent exocytosis in PC12
      cells.

PMID- 9188097
TI  - Fast receptor-induced formation of glycerophosphoinositol-4-phosphate, a putative
      novel intracellular messenger in the Ras pathway.
AB  - Glycerophosphoinositols are phosphoinositide metabolites whose levels are
      constitutively elevated in Ras-transformed cells. Here, we show that one of these
      compounds, glycerophosphoinositol-4-phosphate (GroPIns-4-P) responds acutely to
      the stimulation of the epidermal growth factor receptor, with a fast, massive and
      transient increase. The mechanism leading to GroPIns-4-P formation involves the
      activation of phosphoinositide-3 kinase and the small GTP-binding protein Rac,
      since GroPIns-4-P was neither formed in cells expressing the dominant negative
      form of Rac nor in cells treated with the phosphoinositide-3 kinase inhibitor
      wortmannin. GroPIns-4-P has been previously shown to inhibit adenylyl cyclase.
      Accordingly, epidermal growth factor also decreased the basal, cholera toxin
      stimulated, and forskolin-stimulated cyclic AMP levels with kinetics similar to
      those of GroPIns-4-P formation, suggesting that GroPIns-4-P mediates this
      inhibitory effect. The hormone-induced formation of GroPIns-4-P was detected in
      several cell lines of various origin, suggesting that GroPIns-4-P is a novel
      intracellular messenger of the Ras pathway, possibly able to convey information
      from tyrosine kinase receptors to the cyclic AMP cascade.

PMID- 9188098
TI  - PF20 gene product contains WD repeats and localizes to the intermicrotubule
      bridges in Chlamydomonas flagella.
AB  - The central pair of microtubules and their associated structures play a
      significant role in regulating flagellar motility. To begin a molecular analysis
      of these components, we generated central apparatus-defective mutants in
      Chlamydomonas reinhardtii using insertional mutagenesis. One paralyzed mutant
      recovered in our screen contains an allele of a previously identified mutation,
      pf20. Mutant cells have paralyzed flagella, and the entire central apparatus is
      missing in isolated axonemes. We have cloned the wild-type PF20 gene and
      confirmed its identity by rescuing the pf20 mutant phenotype upon transformation.
      Rescued transformants were wild type in motility and in axonemal ultrastructure.
      A cDNA clone containing a single, long open reading frame was obtained and
      sequenced. Database searches using the predicted 606-amino acid sequence of PF20
      indicate that the protein contains five contiguous WD repeats. These repeats are
      found in a number of proteins with diverse cellular functions including beta
      transducin and dynein intermediate chains. An antibody was raised against a
      fusion protein expressed from the cloned cDNA. Immunogold labeling of wild-type
      axonemes indicates that the PF20 protein is localized along the length of the C2
      microtubule on the intermicrotubule bridges connecting the two central
      microtubules. We suggest that the PF20 gene product is a new member of the family
      of WD repeat proteins and is required for central microtubule assembly and/or
      stability and flagellar motility.

PMID- 9188099
TI  - A chimeric serine/threonine kinase receptor system reveals the potential of
      multiple type II receptors to cooperate with transforming growth factor-beta type
      I receptor.
AB  - Receptor-type serine/threonine kinases (RSKs) have been organized into two
      distinct classes known as types I and II on the basis of sequence similarity.
      However, experiments have shown ligand specificities in the two classes and as a
      result type I and type II receptors can often bind to a common ligand. The
      transforming growth factor-beta- (TGF-beta) specific receptors represent such a
      case, where both type I and II receptors (T beta RI and T beta RII) are observed.
      Of additional interest is the observation that heteromeric associations of type I
      and II receptors can also enable signaling. To further elucidate the function of
      various RSKs, the extracellular domains of both alpha and beta chains from human
      granulocyte-macrophage colony-stimulating factor receptors were linked to
      transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human
      granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T
      beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras
      formed heteromeric complexes, transmitted TGF-beta signals, and were down
      modulated in response to human granulocyte-macrophage colony-stimulating factor.
      However, experiments utilizing these chimeric receptors in different combinations
      revealed that only heteromeric associations of transmembrane cytoplasmic domains
      mediated signaling and down-modulation. Chimeric receptors with transmembrane
      cytoplasmic domains of activin receptor type II and bone morphogenetic protein
      receptor type II also provided signals in conjunction with chimeric T beta RI. As
      a result, these type II receptors may share a common potential to signal via T
      beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification
      and characterization of the divergent signals mediated by individual RSKs.

PMID- 9188100
TI  - Structurally similar Drosophila alpha-tubulins are functionally distinct in vivo.
AB  - We used transgenic analysis in Drosophila to compare the ability of two
      structurally similar alpha-tubulin isoforms to support microtubule assembly in
      vivo. Our data revealed that even closely related alpha-tubulin isoforms have
      different functional capacities. Thus, in multicellular organisms, even small
      changes in tubulin structure may have important consequences for regulation of
      the microtubule cytoskeleton. In spermatogenesis, all microtubule functions in
      the postmitotic male germ cells are carried out by a single tubulin heterodimer
      composed of the major Drosophila alpha-84B tubulin isoform and the testis
      specific beta 2-tubulin isoform. We tested the ability of the developmentally
      regulated alpha 85E-tubulin isoform to replace alpha 84B in spermatogenesis. Even
      though it is 98% similar in sequence, alpha 85E is not functionally equivalent to
      alpha 84B. alpha 85E can support some functional microtubules in the male germ
      cells, but alpha 85E causes dominant male sterility if it makes up more than one
      half of the total alpha-tubulin pool in the spermatids. alpha 85E does not
      disrupt meiotic spindle or cytoplasmic microtubules but causes defects in
      morphogenesis of the two classes of singlet microtubules in the sperm tail
      axoneme, the central pair and the accessory microtubules. Axonemal defects caused
      by alpha 85E are precisely reciprocal to dominant defects in doublet microtubules
      we observed in a previous study of ectopic germ-line expression of the
      developmentally regulated beta 3-tubulin isoform. These data demonstrate that the
      doublet and singlet axoneme microtubules have different requirements for alpha-
      and beta-tubulin structure. In their normal sites of expression, alpha 85E and
      beta 3 are coexpressed during differentiation of several somatic cell types,
      suggesting that alpha 85E and beta 3 might form a specialized heterodimer. Our
      tests of different alpha-beta pairs in spermatogenesis did not support this
      model. We conclude that if alpha 85E and beta 3 have specialized properties
      required for their normal functions, they act independently to modulate the
      properties of microtubules into which they are incorporated.

PMID- 9188101
TI  - Identification of the binding site in intercellular adhesion molecule 1 for its
      receptor, leukocyte function-associated antigen 1.
AB  - Intercellular adhesion molecule 1 (ICAM-1, CD54) is a member of the Ig
      superfamily and is a counterreceptor for the beta 2 integrins: lymphocyte
      function-associated antigen 1 (LFA-1, CD11a/CD18), complement receptor 1 (MAC-1,
      CD11b/CD18), and p150,95 (CD11c/CD18). Binding of ICAM-1 to these receptors
      mediates leukocyte-adhesive functions in immune and inflammatory responses. In
      this report, we describe a cell-free assay using purified recombinant
      extracellular domains of LFA-1 and a dimeric immunoadhesin of ICAM-1. The binding
      of recombinant secreted LFA-1 to ICAM-1 is divalent cation dependent (Mg2+ and
      Mn2+ promote binding) and sensitive to inhibition by antibodies that block LFA-1
      mediated cell adhesion, indicating that its conformation mimics that of LFA-1 on
      activated lymphocytes. We describe six novel anti-ICAM-1 monoclonal antibodies,
      two of which are function blocking. Thirty-five point mutants of the ICAM-1
      immunoadhesin were generated and residues important for binding of monoclonal
      antibodies and purified LFA-1 were identified. Nineteen of these mutants bind
      recombinant LFA-1 equivalently to wild type. Sixteen mutants show a 66-2500-fold
      decrease in LFA-1 binding yet, with few exceptions, retain binding to the
      monoclonal antibodies. These mutants, along with modeling studies, define the LFA
      1 binding site on ICAM-1 as residues E34, K39, M64, Y66, N68, and Q73, that are
      predicted to lie on the CDFG beta-sheet of the Ig fold. The mutant G32A also
      abrogates binding to LFA-1 while retaining binding to all of the antibodies,
      possibly indicating a direct interaction of this residue with LFA-1. These data
      have allowed the generation of a highly refined model of the LFA-1 binding site
      of ICAM-1.

PMID- 9188104
TI  - College on problems of drug dependence presidential address 1996: inhalant abuse,
      a forgotten drug abuse problem.

PMID- 9188102
TI  - Endocytic trafficking of megalin/RAP complexes: dissociation of the complexes in
      late endosomes.
AB  - Megalin (gp330) is a member of the low-density lipoprotein receptor gene family.
      Like other members of the family, it is an endocytic receptor that binds a number
      of specific ligands. Megalin also binds the receptor-associated protein (RAP)
      that serves as an exocytic traffic chaperone and inhibits ligand binding to the
      receptor. To investigate the fate of megalin/RAP complexes, we bound RAP
      glutathione-S-transferase fusion protein (RAP-GST) to megalin at the surface of
      L2 yolk sac carcinoma cells and followed the trafficking of the complexes by
      immunofluorescence and immunogold labeling and by their distribution on Percoll
      gradients. We show that megalin/RAP-GST complexes, which are internalized via
      clathrin-coated pits, are delivered to early endosomes where they accumulate
      during an 18 degrees C temperature block and colocalize with transferrin and
      transferrin receptor. Upon release from the temperature block, the complexes
      travel to late endosomes where they colocalize with rab7 and can be
      coprecipitated with anti-RAP-GST antibodies. Dissociation of the complex occurs
      in late endosomes and is most likely triggered by the low pH (approximately 5.5)
      of this compartment. RAP is then rapidly delivered to lysosomes and degraded
      whereas megalin is recycled to the cell surface. When the ligand, lipoprotein
      lipase, was bound to megalin, the receptor was found to recycle through early
      endosomes. We conclude that in contrast to receptor/ligand complexes, megalin/RAP
      complexes traffic through late endosomes, which is a novelty for members of the
      low-density lipoprotein receptor gene family.

PMID- 9188105
TI  - Introduction of the Nathan B. Eddy Memorial Award.

PMID- 9188103
TI  - Specific release of membrane-bound annexin II and cortical cytoskeletal elements
      by sequestration of membrane cholesterol.
AB  - Annexin II is an abundant protein which is present in the cytosol and on the
      cytoplasmic face of plasma membrane and early endosomes. It is generally believed
      that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism
      typical for the annexin protein family. Although previous studies have shown that
      annexin II is involved in early endosome dynamics and organization, the precise
      biological role of the protein is unknown. In this study, we found that
      approximately 50% of the total cellular annexin was associated with membranes in
      a Ca(2+)-independent manner. This binding was extremely tight, since it resisted
      high salt and, to some extent, high pH treatments. We found, however, that
      membrane-associated annexin II could be quantitatively released by low
      concentrations of the cholesterol-sequestering agents filipin and digitonin. Both
      treatments released an identical and limited set of proteins but had no effects
      on other membrane-associated proteins. Among the released proteins, we
      identified, in addition to annexin II itself, the cortical cytoskeletal proteins
      alpha-actinin, ezrin and moesin, and membrane-associated actin. Our biochemical
      and immunological observations indicate that these proteins are part of a complex
      containing annexin II and that stability of the complex is sensitive to
      cholesterol sequestering agents. Since annexin II is tightly membrane-associated
      in a cholesterol-dependent manner, and since it seems to interact physically with
      elements of the cortical actin cytoskeleton, we propose that the protein serves
      as interface between membranes containing high amounts of cholesterol and the
      actin cytoskeleton.

PMID- 9188106
TI  - Lunch with Dr. Kerr: Nathan B. Eddy Award Lecture.

PMID- 9188107
TI  - Unapproved uses of approved drugs.

PMID- 9188108
TI  - Recommended use of morphine in neonates, infants and children based on a
      literature review: Part 2--Clinical use.
AB  - The indication for morphine use is primarily pain, but also a combined analgesic
      and sedative effect may be the rationale behind morphine administration.
      Paediatric morphine regimens have been reported for children with postoperative
      pain, pain related to cancer, sickle cell crisis pain, burns and AIDS. No dose
      response curve for morphine in neonates, infants or children has been
      established, and different levels for the minimum effective plasma concentration
      have been estimated. The side effects observed in neonates, infants, and children
      are similar to those observed in adults, and neonates do not seem to be more
      susceptible to respiratory depression than older children. Despite shortcomings
      in the knowledge of the pharmacodynamics of morphine, it can be considered safe
      to administer morphine to neonates, infants or children. Initial regimens has
      been calculated from the pharmacokinetic parameters of morphine, but treatment
      must be adjusted according to analgesic effect and incidence of side effects.

PMID- 9188109
TI  - Comparison between three transmucosal routes of administration of midazolam in
      children.
AB  - Midazolam was applied transmucosally in 47 children randomly assigned to three
      different groups. Group N received 0.2 mg.kg-1 nasally, group R 0.5 mg.kg-1
      rectally, and group S 0.2 mg.kg-1 sublingually. All groups were treated 60 min
      prior to a planned i.v. puncture with EMLA. Reliable and valid psychological
      parameters (such as emotional situation, shivering, awareness, respiratory rate
      and facial colour) were scored after premedication and before and after i.v.
      puncture, 20 min after premedication and until induction. A blood sample was
      drawn 10, 30 and 60 min after premedication and the levels of midazolam, alpha
      hydroxy-midazolam, ACTH, glucose and cortisol were measured. In all three groups
      the plasma levels of midazolam 10 min after premedication were higher than 70
      ng.ml-1 (accepted as a sedative level). 30 min after premedication the midazolam
      level in the sublingual group was statistically significantly higher than in the
      nasal group and the psychological parameters in all three groups were
      significantly changed (10 min after premedication). The psychological parameters
      were not significantly different between the three groups over the whole study.
      Sublingual premedication has some advantages (most readily accepted, highest
      plasma levels and lowest deviations) and could be the first choice in
      premedication of children. All three transmucosal applications are safe and well
      accepted, although nasal application was rejected by two of the children.

PMID- 9188110
TI  - Spontaneous breathing with the use of a laryngeal mask airway in children:
      comparison of sevoflurane and isoflurane.
AB  - We compared respiratory parameters during anaesthesia with sevoflurane and
      isoflurane through a laryngeal mask airway (LMA). Children were anaesthetized
      with O2 and air with 2.3% (1MAC) sevoflurane (n = 20) or 1.5% (1MAC) isoflurane
      (n = 20). After insertion of LMA, patients were allowed to breathe spontaneously
      and respiratory rate (RR) and PECO2 were measured (presurgery state). After the
      measurement, anaesthetic concentration was increased to 1.3 MAC (3.0% sevoflurane
      or 2.0% isoflurane) and surgical stimulation was added. Fifteen min after
      incision, the measurements were again performed (during surgery). In the
      sevoflurane group, mean RR and PECO2 were 32 breaths.min-1, and 6.0 kPa (45 mmHg)
      respectively, before surgery, and 35 breaths.min-1 and 7.0 kPa (52 mmHg) during
      surgery. In the isoflurane group, mean RR and PECO2 were 32 breaths.min-1 and 6.1
      kPa (46 mmHg) respectively, before surgery, and 37 breaths.min-1 and 6.7 kPa (52
      mmHg) during surgery. There were no statistical differences between the two
      anaesthetic groups. Clinical respiratory and cardiovascular parameters during
      spontaneous breathing with LMA in children are similar during sevoflurane and
      isoflurane anaesthesia.

PMID- 9188111
TI  - Usefulness of self made introducer for laryngeal mask airway in paediatric
      anaesthesia.
AB  - The usefulness of a self made introducer for laryngeal mask airway (LMA)
      placement was investigated in 251 paediatric patients. Adequate success rate on
      the first attempt and atraumatic insertions were achieved by the introducer with
      minimum experience. The authors concluded that the introducer has significant
      advantages for easy and safe insertions of the LMA in paediatric anaesthesia.

PMID- 9188112
TI  - Plasma bupivacaine levels after fascia iliaca compartment block with and without
      adrenaline.
AB  - Twenty children undergoing unilateral surgery on the thigh received a fascia
      iliaca compartment block using 2 mg.kg-1 of bupivacaine with (Group A) or without
      (Group P) adrenaline 1/200,000. Venous blood samples were taken as 5, 10, 15, 20,
      25, 30, 40, 50 and 60 min after injection and assayed for concentrations of
      bupivacaine. In all subjects an adequate block was produced. Plasma
      concentrations of bupivacaine in Group P were significantly higher than those in
      Group A (P < 0.05). The median maximum plasma concentration (Cmax) was 1.1
      micrograms.ml-1 (range 0.54-1.29 micrograms.ml-1) in Group P and 0.35
      microgram.ml-1 (range 0.17-0.96 microgram.ml-1) in Group A. The median time taken
      to attain Cmax (Tmax) was 20 min (range 10-25 min) in Group P and 45 min (range 5
      50 min) in Group A. The median time to first analgesia was 9.75 h (range 3-15 h)
      in Group P and 10.5 h (range 2.5-21 h) in Group A. The study confirmed the
      efficacy of the fascia iliaca compartment block in children and showed that when
      performed with 2 mg.kg-1 of bupivacaine it is associated with plasma
      concentrations of bupivacaine well within acceptable limits. The addition of
      adrenaline 1/200,000 to the local anaesthetic solution reduces the maximum plasma
      concentration reached.

PMID- 9188113
TI  - Prophylactic antiemetics in children undergoing tonsillectomy: high-dose vs low
      dose ondansetron.
AB  - This randomized, double-blind study assessed the impact of two different doses of
      intraoperative ondansetron on vomiting following tonsillectomy in 240
      preadolescent children in a day care surgical setting. After anaesthesia was
      established by inhalation with N2O/ halothane or intravenously with propofol, the
      subjects were administered the study drug (50 or 150 micrograms.kg-1 ondansetron,
      maximum dose 8 mg). Anaesthesia was maintained with N2O/ halothane. The greater
      dose of ondansetron (150 micrograms.kg-1) had a lower incidence (36% vs 52%) of
      postoperative vomiting (P = 0.01). In-hospital emesis was not a problem with only
      14% of the subjects vomiting. Eight patients sought medical attention for
      vomiting after discharge from hospital. In-conclusion, 150 micrograms.kg-1
      ondansetron is a more effective prophylactic antiemetic than 50 micrograms.kg-1
      ondansetron among children undergoing elective tonsillectomy.

PMID- 9188114
TI  - Acetaminophen or ketorolac for post myringotomy pain in children? A prospective,
      double-blinded comparison.
AB  - Myringotomy with tube placement (BMT) is the most frequent surgical procedure
      performed in children. The purpose of this prospective, double-blinded study was
      to determine if 15 mg.kg-1 of acetaminophen (paracetamol) provides analgesia
      similar to that provided by ketorolac, 1 mg.kg-1, at a lower cost. One-hundred
      and-thirty-two children, ages six months to nine years, scheduled for elective
      BMT were randomized to receive oral acetaminophen or ketorolac 30 min
      preoperatively. An Objective Pain Scale score was assessed upon arrival to the
      PACU and at five, ten and 20 min. Time of awakening, time of PACU and day surgery
      discharge and incidence of vomiting were recorded. Groups were comparable in
      demographics, side effects and time to discharge. Median pain scores were lower
      in the ketorolac group at five and ten min but no differences were seen at
      discharge nor in postdischarge analgesic requirements. Is ten min of better
      analgesia worth the cost of ketorolac? We conclude that the slight analgesic
      benefit from ketorolac does not justify its cost in this setting.

PMID- 9188115
TI  - Parental perceptions, expectations and preferences for the postanaesthetic
      recovery of children.
AB  - Improvements in anaesthesia have led to the introduction of rapid-acting agents
      which quicken recovery and decrease sleepiness. Whether parents believe a rapid
      postanaesthetic recovery is an advantage is unknown. Therefore, we evaluated the
      parental perceptions, expectations and preferences for the postanaesthetic
      recovery of children. One hundred and three parents of children having ambulatory
      surgery completed a structured questionnaire and the results of 101 are
      presented. Results indicate that 93% of parents expect their child to be sleepy
      after surgery. Seventy-four per cent of parents indicated they would prefer their
      child to be sleepy or tired in the first 24 h postoperatively. Eight-five percent
      of parents would not be upset if their child's discharge was delayed up to three
      hours because their child was too sleepy. Finally 45.5% of parents are extremely
      concerned about their child experiencing postoperative pain and 68% believe that
      their child would be in more pain if they recovered rapidly from the anaesthetic.
      These results indicate that rapid recovery from anaesthesia and quick discharge
      from hospital are not key expectations of parents of children admitted for day
      surgery. Parents associate a rapid recovery with more pain. Parents need to be
      more fully informed of the advantages of a rapid recovery and reassured that
      children can recover quickly and completely but at the same time be comfortable
      postanaesthetic.

PMID- 9188116
TI  - A comparison of propofol and other sedative use in paediatric intensive care in
      the United Kingdom.
AB  - The retrospective study was designed to examine the safety of propofol against
      other sedative agents when used by infusion for the sedation of children
      requiring mechanical ventilation. One-hundred-and-ninety-eight patients were
      recruited. One-hundred-and-six received propofol and 92 received other sedative
      agents for durations of 30 min to 156 days and 13 min to 11 days respectively.
      The mean infusion rate of propofol was 3.39 mg.kg-1.h-1. Sixty-one of the 92
      patients in the nonpropofol group received midazolam at a mean infusion rate of
      0.4 mg.kg-1.h-1. Forty-one patients developed clinical metabolic acidosis with
      five falling into the pathological range as defined. Seventeen received propofol
      and 24 another sedative agent. Seventy-eight percent of patients that became
      acidotic were under the age of three. No patients who became acidotic was noted
      to have lipaemic serum. Three of four patients were recorded as having lipaemic
      serum received propofol, however two of these patients along with the patient
      that received midazolam also received Intralipid. Overall mortality was similar
      in both sedation groups with 27 deaths being recorded. Thirteen patients received
      propofol. Five nonfatal adverse events occurred, three in patients that had
      received propofol. The findings of the survey suggest that propofol compares
      favourably with other sedative agents when used for sedating children in a
      paediatric intensive care unit.

PMID- 9188117
TI  - Spinal anaesthesia for a paediatric patient undergoing an image guided invasive
      procedure in the Open Configuration Magnetic Resonance Imaging Unit.

PMID- 9188118
TI  - Anaesthetic management of a child undergoing thoracoscopic removal of a lung
      cyst.
AB  - The anaesthetic management of a child undergoing video-assisted thoracoscopic
      resection of a large lung cyst is described. In particular, we discuss the
      prolonged postoperative stay, which resulted from persistent pneumothorax, and
      his need for substantial analgesia up to the twelfth postoperative day-which
      seemed no shorter than might have been expected following a thoracotomy. While
      other workers have claimed advantages with thoracoscopic operations, in terms of
      reduced pain and morbidity, compared to traditional thoracotomy, we feel that one
      should be aware of the potential for severe postoperative pain in these patients.

PMID- 9188119
TI  - Intraoperative cardiovascular collapse in an infant with Arnold-Chiari
      malformation.
AB  - We report a case of an infant with a diagnosis of Arnold-Chiari malformation who
      developed acute cardiovascular collapse during posterior fossa decompression
      surgery. Haemodynamic manifestations were hypotension and bigeminy characterized
      by resistance to conventional resuscitation. The aetiology was considered to be
      due to brainstem compression exerted to control surgical bleeding from an
      inadvertently lacerated sinus at an unusual site, the rim of the foramen magnum.
      Restoration of blood pressure and disappearance of arrhythmia immediately
      followed removal of the brainstem compression rather than volume or
      pharmacological resuscitation.

PMID- 9188120
TI  - Pulmonary aspiration of gastric contents after a priming dose of vecuronium.
AB  - A case is presented of a 16-year-old girl with ectodermal dysplasia for whom
      dental surgery under general anaesthesia was planned. Following a priming dose of
      vecuronium, and immediately after injection of sodium thiopentone (5 mg.kg-1)
      pulmonary aspiration of gastric contents occurred. It is hypothesized that,
      because of the rapid speed of onset of neuromuscular blocking agents on the
      laryngeal muscles, that partial laryngeal paralysis was present at the time of
      induction of anaesthesia and that this was responsible in part for the episode of
      pulmonary aspiration.

PMID- 9188122
TI  - The 'hourglass' reservoir bag. A closed scavenging system for the Jackson Rees
      modification of Ayre's 'T'-piece.

PMID- 9188121
TI  - Prolonged muscle weakness following emergency tonsillectomy in a patient with
      familial periodic paralysis and infectious mononucleosis.
AB  - A thirteen-year-old girl with normokalaemic familial periodic paralysis (FPP)
      suffered life threatening upper airway obstruction secondary to
      tonsillopharyngitis resulting from infectious mononucleosis (IM). Emergency
      tonsillectomy was performed, but her postoperative course was complicated by
      persistent muscle weakness requiring a very prolonged period of artificial
      ventilation.

PMID- 9188123
TI  - Haemothorax following central line placement.

PMID- 9188124
TI  - Anaesthesia for Hecht Beals syndrome.

PMID- 9188125
TI  - Take your tricks where you see them.

PMID- 9188126
TI  - Issues and challenges: pneumococcal vaccination in pediatrics.

PMID- 9188127
TI  - Recommendations for the use of Haemophilus influenzae type b vaccines among
      children in the United States.

PMID- 9188128
TI  - Rubella immunization.

PMID- 9188130
TI  - Poliomyelitis prevention in the United States: new recommendations for routine
      childhood vaccination place greater reliance on inactivated poliovirus vaccine.
AB  - Until worldwide eradication of poliomyelitis is achieved, vaccination with
      poliovirus vaccines is the only means for providing population and individual
      immunity to polioviruses. The ACIP, AAP, and AAFP support the global
      poliomyelitis eradication initiative, and have recommended a transition policy
      that will increase use of IPV and decrease use of OPV during the next 3 to 5
      years.

PMID- 9188129
TI  - Pertussis vaccination in the United States--new developments and recommendations.

PMID- 9188131
TI  - Live attenuated varicella vaccine.

PMID- 9188132
TI  - Experimental study of ascending Candida albicans pyelonephritis focusing on the
      hyphal form and oxidant injury.
AB  - To investigate the pathogenicity of the hyphal form of Candida in pyelonephritis
      a Candida albicans strain, assuming only the yeast form but not the hyphal form
      when induced by ultraviolet mutagenesis, and a revertant strain from this mutant
      strain showing bimorphism were compared in a rat experimental model with regard
      to the incidence of ascending Candida pyelonephritis and the grade of
      inflammation. To increase the frequency of pyelonephritis unilateral incomplete
      ureteral stenosis was created. The revertant strain assuming the hyphal form
      showed a significantly (p < 0.01) higher frequency of pyelonephritis as compared
      with the mutant strain not assuming this form, and the grade of inflammation was
      also higher in the revertant strain group. Also, higher renal tissue and serum
      levels of both lipid peroxide and superoxide dismutase, which are related to
      marked renal oxidant injury, tended to be correlated with the degree of
      neutrophil infiltration in the acute phase. These findings suggest that the
      hyphal form plays an important role in the development of C. albicans
      pyelonephritis and also that the oxygen radicals from neutrophils appearing at
      the sites of inflammation play a major part in the further extension of
      inflammatory lesions.

PMID- 9188133
TI  - Influence of furosemide on the ureteric damage in a rat model of obstructive
      uropathy.
AB  - Furosemide has been used in the diuretic renography and diuretic radionuclide
      scan to evaluate the severity of hydroureter and hydronephrosis. To elucidate the
      influence of furosemide on obstructed ureters, unilateral ligation of ureter was
      performed in 45 rats. Twenty-four of the rats received intramuscular injections
      of furosemide (6 mg/kg/day) after the third day postligation. Eight rats were
      sacrificed for examination on days 7, 10 and 14 after ligation, respectively. The
      remaining 21 untreated rats were also sacrificed for comparison. The severity of
      hydroureter and hydronephrosis in the ligated side of the furosemide-treated rats
      was significantly higher than that of the untreated rats. However, the
      histological changes in the treated and untreated rats showed no significant
      difference. The ultrastructural alterations aggravated along the course of
      ureteric obstruction. Intriguingly, the ultrastructural changes were
      significantly milder in the treated rats. We conclude that the administration of
      furosemide might increase the severity of hydroureter, but it does not accelerate
      the ureteric damage of the obstructed ureters.

PMID- 9188134
TI  - Polidocanol sclerotherapy for simple renal cysts.
AB  - Simple renal cysts were treated by aspiration and injection of the sclerosing
      agent 3% polidocanol (Aetoxisclerol) in 15 patients. All patients were followed
      up by ultrasound for 1-24 months. The age ranged from 35 to 81 years. There was 1
      recurrence at 1 month. The efficacy of this treatment was 93%. Fourteen cysts
      completely disappeared, and no recurrence occurred after 1 year. Complications,
      such as microscopic hematuria, fever and infection, were not observed. The
      technique of polidocanol sclerotherapy was effective and safe.

PMID- 9188135
TI  - Autonomic hyperreflexia revisited.
AB  - PURPOSE: To analyze autonomic hyperreflexia (AHR) associated with neurogenic
      bladder dysfunction in high spinal cord-injured patients. MATERIAL AND METHODS:
      Sixty-five patients were examined using a new recording system. Seventeen
      suffered from a spinal cord lesion above the T5-T6 level and presented with
      neurogenic voiding disorders and AHR. Mean arterial pressure (MAP) changes were
      analyzed during 3 different urodynamic phases: bladder filling; isometric bladder
      contraction, and voiding. RESULTS: Of the 17 tetraplegic and high paraplegic
      patients, 6 dropped out and 11 entered the study. Nine of these eleven patients
      displayed uninhibited bladder contractions and voiding. In these 9 cases MAP
      increased progressively during bladder contraction until a maximal bladder
      pressure was reached. An ongoing elevation of MAP was observed during voiding
      which returned to normal values within 5 min after micturition. In 2 patients
      detrusor-sphincter dyssynergia prevented voiding. As opposed to the 9 previously
      mentioned patients, maximal MAP occurred at or before the maximal bladder
      pressure in these 2 cases and decreased thereafter. CONCLUSIONS: Evidence is
      presented that the posterior urethral receptors and their ascending pathway
      played a major role in the maintenance of AHR during micturition.

PMID- 9188136
TI  - Effects of ageing and X-irradiation on the diurnal rhythm of mouse urinary
      bladder capacity.
AB  - The effect of single-dose irradiation (19 Gy) or sham treatment on circadian
      variations in urinary bladder storage capacity was assessed during a 250-day
      period following treatment using transurethral cystometry under anesthesia.
      Changes in bladder function were quantified as the deviation from individual
      pretreatment values of bladder volume at defined intravesical pressures. A marked
      diurnal rhythm with a peak at 19.00 h and an extended nadir between 1.00 h and
      12.00 h was found in 11- to 12-week-old untreated mice. No systematic changes in
      bladder function with age could be observed in repeated cystometries after sham
      treatment. X-Irradiation resulted in a triphasic response. After an early
      reversible decrease in bladder capacity (acute phase) complete recovery was
      observed within 30 days after irradiation. Following a symptom-free latent period
      of about 15 weeks, chronic progressive impairment of bladder storage function
      developed (chronic phase). During the acute and latent period, no changes in the
      diurnal pattern were observed. In the late phase, not only a decrease in the
      absolute capacity values but also in the amplitude of diurnal fluctuations was
      seen. The daily minimum values, however, were still found between 1.00 and 12.00
      h. The data indicate that cystometry values obtained between 8.00 and 12.00 h
      provide suitable parameters for the quantification of radiation effects in the
      urinary bladder in longitudinal studies.

PMID- 9188137
TI  - Clinical outcome and quality of life after enterocystoplasty for contracted
      bladders.
AB  - From 1989 to 1995, a total of 21 patients underwent enterocystoplasty in order to
      increase their bladder capacity and decrease intravesical pressure. Of these, 18
      had neuropathic bladders caused by spinal cord injuries and 3 had contracted
      bladders caused by irradiation cystitis following treatment of cervical cancer.
      Enterocystoplasty was performed using a 40-cm segment of terminal ileum. The
      postoperative follow-up periods ranged from 6 to 80 months (mean 36 months).
      Twelve patients, who had had preoperative hydronephrosis, showed complete
      resolution after enterocystoplasty. Sixteen patients, suffering from intractable
      urinary incontinence preoperatively, regained continence after surgery while 2
      continued to have mild urgent or stress incontinence. Their mean bladder
      capacities were 165 +/- 97 ml preoperatively and 760 +/- 289 ml postoperatively.
      The end-filling pressures were 50 +/- 23 cm H2O preoperatively and 13 +/- 4.7 cm
      H2O postoperatively. Sixteen patients could urinate smoothly, but 12 of them
      occasionally needed intermittent catheterization in order to evacuate residual
      urine. Nineteen patients were satisfied with their surgical result, whereas 1
      wished to become completely dry, and 1 could not be catheterized because of poor
      family support. All but 1 of the patients declared that the quality of life
      improved after surgery. In conclusion, enterocystoplasty is satisfactory
      treatment for contracted bladders that result in upper tract deterioration or
      intractable urinary incontinence. Acceptable continence was achieved in 90% of
      the patients and the overall satisfaction rate was 95%. Careful patient selection
      is necessary for achieving a good surgical outcome.

PMID- 9188138
TI  - Cytogenetic survey of 1,007 infertile males.
AB  - The aim of this study was to investigate the influence of a chromosome
      abnormality on male infertility. The subjects consisted of 1,007 males with the
      chief complaint of infertility. Karyotyping was conducted mainly by G banding.
      Major chromosome abnormalities were observed in 62 patients (6.2%) in total and
      consisted of sex chromosome abnormalities were observed in 62 patients (6.2%) in
      total and consisted of sex chromosome abnormalities in 38 patients (3.8%) and
      autosomal chromosome abnormalities in 24 (2.4%). Among the patients with sex
      chromosome abnormalities, 28 cases were 47, XXY, 3 were 47,XYY, and 7 cases had a
      Y chromosome abnormality. Autosomal chromosome abnormalities comprised 10 cases
      of reciprocal translocation, 8 cases of Robertsonian translocation, 5 cases of
      inversion, and 1 case of ring chromosome. In patients with a sperm density < 5 x
      10(6)/ml, a total motile sperm count < 1 x 10(6), a follicle-stimulating hormone
      value > or = 30.1 mIU/ml, a luteinizing hormone value > or = 8.9 mIU/ml, a
      testosterone value < or = 2.69 ng/ml, or an average testis volume < or = 8 ml,
      the incidence of major chromosome abnormalities was significantly higher. These
      findings suggest that patients who need microinsemination should undergo
      chromosome analysis. We should counsel patients about obtaining adequate
      information on each chromosome abnormality.

PMID- 9188139
TI  - Epididymal sperm retrieval by epididymal micropuncture combined with
      intracytoplasmic sperm injection: difference between acquired and congenital
      irreparable obstructive azoospermia.
AB  - To evaluate the differences in fertilization and pregnancy rates following
      intracytoplasmic sperm injection (ICSI) of retrieved epididymal sperm between
      congenital (group 1) and acquired (group 2) unreconstructable obstructive
      azoospermic patients, we compared the outcome of the ICSI procedure between these
      two groups. Thirty-six patients with obstructive azoospermia received epididymal
      sperm retrieval by the micropuncture method for the ICSI procedure. Main
      parameters evaluated were epididymal fluid volume, sperm concentration, sperm
      motility; fertilization rate and clinical pregnancy rate. There were no
      significant differences in epididymal fluid and sperm concentration between the
      two groups. However, the sperm motility in group 1 was significantly higher than
      that in group 2. The fertilization rates per couple in groups 1 and 2 were 78.2
      and 82% (nonsignificant). The pregnancy rate per couple in group 1 was 37.5%
      (6/16), while that in group 2 was only 5% (1/20); this difference was
      statistically significant (p < 0.05). Using epididymal sperm for the ICSI
      procedure, the chances of pregnancy for couples with congenital absence of the
      vas deferens were significantly higher compared with couples with acquired
      unreconstructable obstructive male infertility.

PMID- 9188140
TI  - Is diabetic neuropathy responsible for diabetic impotence?
AB  - It is well known that diabetes mellitus is accompanied by complications of sexual
      dysfunction and it is believed that diabetic neuropathy may cause impotence. In
      our study, we found that not all the patients who visited our center with the
      chief complaint of diabetic impotence were suffering from organic impotence, and
      diabetes mellitus per se served as a means of psychological stress in a
      substantial number of cases. Probably because no method has been available to
      provide precise information on the state of the penile-controlling nerves, we
      found that a larger number of patients than expected were suffering from a
      vascular disorder.

PMID- 9188141
TI  - Giant adrenal cyst: preoperative diagnosis and management.

PMID- 9188142
TI  - Ureteral xanthine calculus and aberrant umbilical artery causing ureteral
      obstruction.
AB  - A 30-month-old girl presented with gastrointestinal symptoms and a febrile
      urinary tract infection. Sonographic and radiographic imaging demonstrated left
      hydronephrosis due to a radiolucent ureteral stone. Surgical exploration
      identified an aberrant, patent left umbilical artery causing ureteral
      obstruction. Stone and urine analyses revealed hereditary xanthinuria that had
      not previously been recognized in this child and her family.

PMID- 9188143
TI  - Pure silicate fragment in a recurrent stone former of calcium oxalate.
AB  - Long-time oral intake of magnesium-silicate-containing drugs is thought to be a
      causative factor inducing silicate urolithiasis. Besides, magnesium seems to play
      an anti-urolithogenic part in the formation of calcium oxalate stones. We report
      a recurrent calcium oxalate former who had been treated with magnesium
      aluminometasilicate antacid for gastric ulcer for approximately 17 years. One of
      the fragments found during extracorporeal shock wave lithotripsy was identified
      as 100% silicate. Deposition of silica was also found on other fragments. A large
      dose of magnesium (given in a part of the drug) might have little influence on
      the formation of calcium oxalate.

PMID- 9188144
TI  - Primary vaginal urinary calculus following abdominoperineal resection of rectum.
AB  - A rare case of primary vaginal calculus is presented. The case is unusual since
      it occurred after abdominoperineal resection for carcinoma rectum. The mechanism
      of stone formation in the patient has been discussed.

PMID- 9188145
TI  - Melanosis coli--a harmless pigmentation or a precancerous condition?
AB  - Melanosis coli has long been considered as a harmless pigmentation of the
      colorectum associated with the use of laxatives containing anthraquinone. Recent
      experimental and clinical studies, however, have provided some evidence of a
      possible association between melanosis coli/laxative use and colorectal cancer.
      METHODS: In 2.229 consecutive patients we retrospectively analyzed the
      association of melanosis coli and laxative use with colorectal neoplasia. All the
      patients had undergone total colonoscopy, and the colorectal neoplasias had been
      examined histopathologically in accordance with the WHO classification.
      Information concerning laxative use, bowel habits and family history of
      colorectal cancer was obtained from the medical records. The statistical analysis
      was done using the Mantel-Haenszel-test for linear association. RESULTS: The
      presence of colorectal cancer was not associated with melanosis coli or laxative
      use. However, colorectal adenomas were found significantly more frequently in
      patients with melanosis coli than in those without melanosis (p = 0.0002). But
      adenomas associated with melanosis coli were significantly smaller than those not
      associated with melanosis (p < 0.0001), and were located predominantly in the
      proximal colon (p = 0.0002). In the patients with melanosis coli the relative
      risk was significantly higher for tubular (1.80; 95% CI: 1.26-2.56) and
      tubulovillous adenomas (2.03; 95% CI: 1.09-3.76), but not for villous adenomas.
      No significant differences were found in the grade of dysplasia of adenomas in
      patients with, and those without, melanosis coli. CONCLUSION: There appears to be
      no association between colorectal cancer and melanosis coli or laxative use.
      Colorectal adenomas are more frequently found in patients with melanosis coli.
      Colorectal adenomas do not contain the melanin-like pigmentation. The association
      of adenomas with melanosis coli can be explained by the ease of detection of even
      tiny polyps as white spots within a dark-colored colonic mucosa.

PMID- 9188146
TI  - Ciguatera fish poisoning following travel to the tropics.
AB  - A 40-year-old man-as well as 15 more participants of the same meal-suddenly
      experienced vomiting and watery diarrhea four hours after having eaten a meal of
      grouper in the Dominican Republic. Symptoms persisted for four hours and were
      followed by a generalized pruritus and paresthesias of the lips, tongue, palms,
      and soles of the feet. Physical examination was normal with the exception of a
      pulse of 45 beats per minute, a blood pressure of 80/50 mmHg, and paradoxical
      temperature perception. Laboratory values were regular except for the erythrocyte
      sedimentation rate of 40 mm per hour. 24-hour Holter electrocardiogram showed a
      normal sinus rhythm with impaired heart rate variability (37-100 beats per
      minute). Due to the typical history and the clinical findings, ciguatera toxin
      ingestion was diagnosed. Pruritus decreased slightly with symptomatic therapy,
      but it took 16 weeks for all symptoms to resolve. Ciguatera fish poisoning is
      rare in temperate countries. Symptoms of this neurotoxic disease are
      gastrointestinal, neurologic, and cardiovascular manifestations with
      paresthesias, paradoxical sensor disturbances, and muscular weakness as well as
      bradycardia and hypotension. With travel to and from the tropics and increasing
      imports of tropical fish ciguatera will be of growing importance even in
      nontropical areas.

PMID- 9188147
TI  - Immune responses towards intestinal bacteria--current concepts and future
      perspectives.
AB  - The intestinal mucosa constitutes an important barrier as it separates each
      individual from a large array of antigens within the bowel lumen. These luminal
      antigens may either be derived from pathogens or may be derived from harmless
      constituents such as ingested food or the normal intestinal flora. The dichotomy
      of potentially harmful and potentially harmless antigens encountered by the
      mucosal immune system poses the important task that, with regard to bacteria
      derived antigens, the gut associated immune system is required to mount an
      efficient host defense against pathogenic bacteria but to maintain at the same
      time the regulatory control mechanisms which protect the human organism from
      hyperresponsiveness, and thus chronic inflammation, towards antigens from the
      normal intestinal flora. In the present review, we discuss variable host and
      bacterial factors which are likely to determine whether the immune response to
      pathogenic or normal intestinal bacteria will have beneficial or detrimental
      consequences for the human organism. Using infections with the prototype
      enteropathogens V. cholerae and enteropathogenic E. coli (ETEC), Y.
      enterocolitica induced reactive arthritis (ReA) and in more detail, inflammatory
      bowel diseases (IBD) as exemplary clinical situations, we review current
      hypotheses of how bacteria or their products are encountered by cellular
      components of the specific immune system and how this may relate to disease
      pathogenesis and the development of new treatment strategies.

PMID- 9188148
TI  - Expression of recombinant glycoproteins in the simple eukaryote Dictyostelium
      discoideum.

PMID- 9188149
TI  - Bioreactor cultivation of the nematode Caenorhabditis elegans: large scale
      production of biologically active drug receptors for pharmaceutical research.

PMID- 9188150
TI  - Harvesting molecular diversity--biology's new commodity.

PMID- 9188151
TI  - A chemist's perspective on the use of genetically engineered microbes as reagents
      for organic synthesis.

PMID- 9188152
TI  - Microbial laser light scattering.

PMID- 9188153
TI  - Novel bioconversions for the production of designer antioxidant and colourant
      flavonoids using polyphenol oxidases.

PMID- 9188154
TI  - Engineering nutritious proteins.

PMID- 9188155
TI  - Enzyme thermostabilization: the state of the art.

PMID- 9188156
TI  - Casein and peptide degradation in lactic acid bacteria.

PMID- 9188157
TI  - Commercial production of lactoferrin, a multifunctional iron-binding
      glycoprotein.

PMID- 9188158
TI  - Subcellular targeting and purification of recombinant proteins in plant
      production systems.

PMID- 9188159
TI  - Biotechnology of protein and polysaccharide gels.

PMID- 9188161
TI  - Analysis of interacting biopolymer systems by analytical ultracentrifugation.
AB  - Many of the functions of biological macromolecules are based on specific
      interactions. Extended concentration dependent studies of sedimentation
      coefficients or molecular masses of biopolymers are highly useful for describing
      the different kinds of association phenomena. These studies allow one to
      determine the partial concentrations of monomers and associates or reactants and
      complexes in self-associating systems or heterologous associations, respectively.
      Furthermore, in combination with corresponding measurements of biological
      activity these data allow one to estimate the individual activity parameters of
      components involved in equilibrium processes. The study of self-association and
      heterologous association using analytical ultracentrifugation, some recent
      developments therein, and its application to different examples are outlined
      here.

PMID- 9188160
TI  - Structure of cellulases and their applications.

PMID- 9188162
TI  - An artificial HIV enhancer-binding peptide is dimerized by the addition of a
      leucine zipper.
AB  - A 42 residue artificial peptide that binds to the HIV-1 enhancers has been
      described previously. The specificity of interaction of the peptide with its
      target DNA sequence has been demonstrated by a variety of techniques. Naturally
      occurring regulatory proteins frequently bind to DNA as dimers, thereby
      increasing the strength and specificity of the interaction, the dimer interface
      often being provided by a leucine zipper type coiled coil. As a suitable binding
      site for this kind of system is located to the 5' end of the HIV enhancer region,
      it was decided to design and synthesize a fusion peptide that not only contained
      the DNA binding sequence of the original 42 residue peptide but also incorporated
      a leucine zipper based on that of the GCN4 transcriptional activator, that
      should, therefore, be capable of dimerizing. The resultant peptide, LZ66, has now
      been shown to be fully active in band shift and in vitro transcription assays and
      to exhibit about double the inhibitory activity of the parent 42 residue peptide.
      Preliminary CD measurements revealed that the peptide has a high alpha-helical
      content and that it adopts a stable conformation down to the low micromolar
      peptide concentration range. Sedimentation equilibrium studies confirmed that the
      principles involved in the design of the peptide are valid and that the peptide
      is indeed dimeric in solution.

PMID- 9188163
TI  - Alteration of the quaternary structure of glutamate dehydrogenase from
      Clostridium symbiosum by a single mutation distant from the subunit interfaces.
AB  - X-ray crystallographic studies have previously shown that glutamate dehydrogenase
      from Clostridium symbiosum is a homohexamer. Mutation of the active-site
      aspartate-165 to histidine causes an alteration in the structural properties of
      the enzyme. The mutant enzyme, D165H exists predominantly as a single species of
      lower molecular mass than the wild-type enzyme as indicated by gel filtration and
      sedimentation velocity analysis. The latter technique gives an S20,w value for
      D165H of (6.07 +/- 0.01)S which compares with (11.08 +/- 0.01)S for the wild
      type, indicative of alteration of the homohexameric quaternary structure of the
      native enzyme to a dimeric form, a result confirmed by sedimentation equilibrium
      experiments. Further support for this is provided by chemical modification by
      Ellman's reagent of cysteine-144 in the mutant, a residue which is buried at the
      dimer-dimer interface in the wild-type enzyme and is normally inaccessible to
      modification. The results suggest a possible structural route for communication
      between the active sites and subunit interfaces which may be important for
      relaying signals between subunits in allosteric regulation of the enzyme.

PMID- 9188164
TI  - DT diaphorase exists as a dimer-tetramer equilibrium in solution.
AB  - The quaternary behaviour of DT diaphorase in solution has been investigated by
      hydrodynamics under a range of conditions. At neutral pH DT diaphorase is shown
      to exist as a tightly-associated homodimer in a dimer-tetramer equilibrium.
      Concentrations of the chaotropic agent potassium thiocyanate (KSCN) of greater
      than 200 mM result in irreversible loss of the FAD cofactor and denaturation of
      the homodimer though this agent appears to be ineffective in disrupting
      intermolecular association. These data conform to a model in which under extreme
      dissociation conditions, the folded dimer is in equilibrium with the unfolded
      monomer and are consistent with evidence from the X-ray structure and proposed
      catalytic mechanism where both monomers are catalytically interdependent.

PMID- 9188166
TI  - A case study and use of sedimentation equilibrium analytical ultracentrifugation
      as a tool for biopharmaceutical development.
AB  - Analytical ultracentrifugation (AUC) has reemerged as a powerful technique for
      protein characterisation. We report the pivotal role sedimentation equilibrium
      AUC has played in the development of macrophage inflammatory protein-1 alpha (MIP
      1 alpha) as a protein therapeutic. MIP-1 alpha has potential clinical
      applications in cancer but its clinical use is limited, since it associates to
      form large insoluble aggregates in physiological buffers. Using AUC as a
      screening technique, we have produced a biologically active variant of MIP-1
      alpha, BB-10010, which has a reduced tendency to aggregate in physiological
      buffers. The aggregation of protein based pharmaceuticals is routinely monitored
      by size exclusion chromatography (SEC). Comparison of the data acquired by SEC
      and AUC, demonstrates that owing to the complexity of BB-10010, AUC analysis is
      required in addition to SEC to provide a rigorous characterisation of molecular
      association. This work has been extended to include the use of AUC as an
      analytical tool to monitor the quality of BB-10010 during formulation and
      stability studies.

PMID- 9188167
TI  - Interaction of detergents with bovine lens alpha-crystallin: evidence for an
      oligomeric structure based on amphiphilic interactions.
AB  - We have studied the quaternary structure of alpha-crystallin in the presence of
      increasing concentrations of amphiphilic and neutral detergents using gel
      filtration, light-scattering, boundary and equilibrium sedimentation. We observed
      a continuous reduction of the molar mass of the polymeric alpha-crystallin on
      increasing the concentration of sodium dodecyl sulphate from 0.1 mM to 5 mM,
      ending up with the monomeric peptides. Dodecyltrimethylammonium bromide also
      disrupts the oligomeric structure of alpha-crystallin but the interaction appears
      to be cooperative: in the sharp transition region (for a 1 mg/ml protein
      solution) from 3 to 8 mM of the detergent, only the native protein and a mixture
      of monomeric and dimeric peptide-DTAB complexes can be observed. Concomitant
      studies of the circular dichroism in the far UV revealed a substantial decrease
      of the beta-sheet and increase of the alpha-helix secondary structure. The latter
      can be related to the presence of amphiphilic polypeptide sequences in the
      constituent alpha A and alpha B peptides. These studies reveal for the first time
      a direct relation between changes in the secondary structure of the alpha A and
      alpha B peptides and the formation of the oligomeric alpha-crystallin structure:
      the binding of the amphiphilic detergent reduces the beta-sheet content, induces
      the formation of alpha-helix secondary structure and reduces the tendency of the
      peptide to form large aggregates. The different mechanisms for reducing the
      oligomeric size by anionic and cationic detergents with identical apolar parts
      stresses the importance of charge interactions. Our findings support some aspects
      of the micelle model of alpha-crystallin and can be related to its chaperone
      activity.

PMID- 9188165
TI  - Further analysis of the role of spectrin repeat motifs in alpha-actinin dimer
      formation.
AB  - Protein constructs consisting of repeats 1-4, repeats 1-3 and repeats 2-4 of the
      rod domain of chicken alpha-actinin were expressed as fusion proteins in
      Escherichia coli. Based on the evidence of circular dichroism spectra and
      cooperative thermal unfolding profiles both truncated rod fragments were judged
      to have assumed the native structural fold. The thermal stabilities were in both
      cases significantly lower than that of the intact rod (repeats 1-4). Analyses by
      sedimentation equilibrium and velocity provided further evidence to show that
      fragment 1-4 is entirely dimeric in the concentration range of these experiments,
      resembling therefore the rod domain isolated by proteolytic digestion of native
      alpha-actinin. Fragment 2-4, and probably also 1-3, show concentration-dependent
      association, with dissociation constants, estimated by sedimentation equilibrium,
      in the 1-10 microM range. Thus, in confirmation of earlier work, all four repeats
      are required to generate a maximally stable anti-parallel dimer (Kd approximately
      10 pM), suggesting the presence of binding sites in all of them to allow for
      aligned pairing.

PMID- 9188168
TI  - Characterisation of the low affinity interaction between rat cell adhesion
      molecules CD2 and CD48 by analytical ultracentrifugation.
AB  - CD2 is a cell adhesion molecule found on the plasma membrane of T-lymphocytes.
      Its counter-receptor in rat is the structurally related CD48. This interaction is
      believed to contribute to the adhesion of T-cells to other cells such as
      cytotoxic targets and antigen presenting cells. Cell-cell adhesion involves the
      formation of multiple cell adhesion molecule complexes at the cell surface and if
      cell-cell de-adhesion is to occur, these complexes need to be disrupted. The
      affinities of cell adhesion molecule interactions are suggested to be relatively
      weak to allow this de-adhesion of cell-cell interactions. The CD2/CD48
      interaction has been studied using recombinant extracellular proteins and the
      affinity of the interaction of soluble recombinant rat CD2-CD48 has been
      determined (at 37 degrees C) using surface plasmon resonance (and shown to be
      weak), with the dissociation constant Kd = 60-90 microM. The values determined by
      surface plasmon resonance results could be affected by the immobilisation of the
      ligand on the chip and any self-association on the chip. We used three different
      analytical ultracentrifuge procedures which each allowed the interaction to be
      studied in free solution without the need for an immobilisation medium. Both
      sedimentation equilibrium (using direct analysis of the concentration
      distribution and also modelling of molecular weight versus concentration data)
      and sedimentation velocity at 5 degrees C yielded dissociation constants in the
      range of 20-110 microM, supporting the surface plasmon resonance findings showing
      that binding between these cell adhesion molecules is relatively weak. These
      studies also ruled out the presence of any significant self-association of the
      reactants which could lead to systematic error in the surface plasmon resonance
      results.

PMID- 9188169
TI  - Automated hydrodynamic modelling of a complex between a human IgE fragment (Fc
      epsilon 3-4) and the IgE high affinity receptor Fc epsilon RI alpha-chain.
AB  - The binding of IgE to its high affinity receptor Fc epsilon RI plays an important
      role in the allergic response. The interaction between soluble Fc epsilon RI
      alpha-chain (sFc epsilon RI alpha) and Fc epsilon 3-4, a fragment of IgE
      consisting of the C epsilon 3 and C epsilon 4 heavy chain constant domains, has
      been studied using analytical ultracentrifugation (Keown et al. this volume).
      Here we describe the development of a simple automated hydrodynamic modelling
      technique and its application to this interaction. This procedure utilises sphere
      models of the two molecules and performs an automated systematic translational
      search of sFc epsilon RI alpha relative to Fc epsilon 3-4. The result of this is
      the generation of 40,359 individual models of how the receptor can be placed
      relative to Fc epsilon 3-4. These are then assessed for consistency by comparing
      the sedimentation coefficients generated for the models to the experimentally
      determined sedimentation coefficients, and are displayed graphically to show
      allowed and disallowed complexes. From this analysis, it is clear that the
      complex between sFc epsilon RI alpha and Fc epsilon 3-4 is compact, with the most
      elongated models being excluded. In addition, sFc epsilon RI alpha appears not to
      interact with the C-terminal end of Fc epsilon 3-4, and probably binds either to
      the sides or face, observations which are consistent with other experimental data
      on the Fc epsilon RI alpha/IgE interaction. Automated hydrodynamic modelling also
      has the potential to be used for other interactions, providing a simple way of
      looking at a large number of models, and making rigorous studies of interacting
      components more feasible.

PMID- 9188170
TI  - Basis of the 1:1 stoichiometry of the high affinity receptor Fc epsilon RI-IgE
      complex.
AB  - A soluble fragment of the high-affinity IgE receptor Fc epsilon RI alpha-chain
      (sFc epsilon RI alpha) binds to the Fc fragment of IgE (IgE-Fc) as a 1:1 complex.
      IgE-Fc consists of a dimer of the C epsilon 2, C epsilon 3 and C epsilon 4
      domains of the epsilon-heavy chain of IgE. This region of IgE has been modelled
      on the crystal structure of the Fc region of IgG1, which exhibits twofold
      rotational symmetry. This implies that IgE should be divalent with respect to its
      ligands. X-ray scattering studies reveal however that the twofold rotational
      symmetry of IgE-Fc is perturbed by a bend in the linker region between the C
      epsilon 2 and C epsilon 3 domains. The 1:1 stoichiometry could then arise from
      the conformational asymmetry or from steric occlusion of one of the sites by the
      overhanging C epsilon 2 domains. To test this hypothesis we have expressed a
      recombinant epsilon-chain fragment containing C epsilon 3 and C epsilon 4. This
      product, Fc epsilon 3-4, is secreted from cells as a disulphide linked dimer and
      binds with higher affinity than either IgE or IgE-Fc to cell surface Fc epsilon
      RI. Titration experiments, together with molecular mass measurements of the Fc
      epsilon 3-4/sFc epsilon RI alpha complex, reveal that Fc epsilon 3-4 binds only a
      single receptor molecule. This excludes the possibility that steric hindrance by
      C epsilon 2 accounts for the unexpected stoichiometry.

PMID- 9188171
TI  - A polydisperse linear random coil model for the quaternary structure of pig
      colonic mucin.
AB  - The distribution of molecular weights for polymeric colonic mucus glycoprotein or
      "mucin" isolated and solubilised in the presence of protease inhibitors from pig
      colons is shown to be considerably greater than its "subunit" (thiol reduction
      product) and papain digested forms using the technique of size-exclusion
      chromatography coupled to multi-angle laser light scattering, and confirmed by
      sedimentation equilibrium measurements. The conformation of this mucin is probed
      by examining the molecular weight-intrinsic viscosity relationship in terms of
      the Mark-Houwink-Kuhn-Sakurada analysis for its polymeric (or "whole"), reduced
      and papain-digested forms: an exponent "a" of (1.1 +/- 0.1) is obtained
      indicating a linear random coil conformation consistent with other mucins. Size
      exclusion chromatography coupled to multi-angle laser light scattering is shown
      to provide a relatively simple complementary technique to sedimentation
      equilibrium for the molecular weight distribution analysis of polydisperse
      materials.

PMID- 9188172
TI  - Spermatozoon and spermiogenesis in Mesocoelium monas (Platyhelminthes:Digenea):
      ultrastructure and epifluorescence microscopy of labelling of tubulin and
      nucleus.
AB  - Spermiogenesis and the spermatozoon were studied in the digenean Mesocoelium
      monas Rudolphi, 1819 (from the toad Bufo sp. in Gabon). An ultrastructural study
      revealed that spermiogenesis follows the usual pattern found in digeneans, i.e.
      proximo-distal fusion of axonemes with a median cytoplasmic process followed by
      elongation. The spermatozoon has two fully incorporated axonemes with the 9 +"1"
      trepaxonematan pattern. Indirect immunofluorescence localization of tubulin and
      fluorescent labelling of the nucleus were used to obtain additional information
      on the structure of the spermatozoon. It was thus shown that one of the axonemes
      is slightly shorter than the other (190 versus 220 microns) and that the filiform
      nucleus (65 microns in length) is located at the distal extremity of the
      spermatozoon (220 microns in length). Various monoclonal and polyclonal
      antibodies, specific to alpha, beta, acetylated-alpha, or general tubulin, were
      used and produced similar labelling.

PMID- 9188173
TI  - Some nematodes of freshwater fishes in Venezuela.
AB  - The present paper comprises a systematic survey of nematodes found in 88
      specimens of 24 species of freshwater fishes in Venezuela in 1992 and 1994. The
      following 13 species of nematodes were recorded: Adults; Guyanema longispiculum
      Moravec, Prouza et Royero, 1996, Guyanema sp., Procamallanus (Spirocamallanus)
      inopinatus Travassos, Artigas et Pereira, 1928, P. (S.) krameri (Petter, 1974)
      comb. n., P.(S.) pintoi (Kohn et Fernandes, 1988) comb, n., Procamallanus
      (Spirocamallanus) sp., Raphidascaris (Sprentascaris) mahnerti (Petter et Cassone,
      1984). Larvae: Anisakidae gen. sp., Brevimulticaecum sp., Contracaecum sp. Type
      1, Contracaecum sp. Type 2, Contracaecum sp. Type 3, Eustrongylides sp. All these
      parasites are reported from Venezuela for the first time and all findings
      represent new host records. Brevimulticaecum larvae are reported from fishes for
      the first time. Almost all parasites are briefly described and illustrated and
      problems concerning their morphology, taxonomy, hosts and geographical
      distribution are discussed. A new name, Terranova diazungriai nom.nov. is
      proposed for T. caballeroi Diaz-Ungria, 1968 (a junior homonym of T. caballeroi
      Barus et Coy Otero, 1966).

PMID- 9188174
TI  - Toxocara canis (Nematoda:Ascaridae): the fine structure of the oviduct, oviduct
      uterine junction and uterus.
AB  - The fine structure of the oviduct, oviduct-uterine junction and uterus of the
      nematode Toxocara canis (Werner, 1782) is described. Columnar-type epithelioid
      cells with numerous microvilli at the apical membrane border the oviduct lumen.
      Many electron dense secretory products are present in these cells. The cells
      lining the oviduct-uterine junction have no microvilli. They are coated with an
      electron-dense layer and contain numerous membrane-bound dense material
      containing bodies. Externally, the cells are surrounded by a basal lamina and
      muscle cells. The epithelial cells lining the greater part of the paired uteri
      appear to be rather flat. The oocytes inside the oviduct are covered with a dense
      thick plasma membrane and contain lipid droplets, dense granules and glycogen.
      The morphology of the oocytes before the fertilization inside the oviduct-uterine
      junction resembles that of the oocyte in the oviduct. After the fertilization the
      egg shell formation takes place. The egg shell of T.canis is composed of four
      layers: uterine, vitelline, middle chitinous and inner layer. The differences
      between the fine structure of the egg shell of T. canis and other related
      nematodes are discussed.

PMID- 9188175
TI  - Two hemocyte populations in Triatoma infestans: ultrastructural and lectin
      binding characterization.
AB  - Two distinct hemocyte populations are determined in the hemolymph of the
      triatomine bug Triatoma infestans Klug, oenocytoids and plasmatocytes, and their
      independent origin from separate stem cells is shown. Both hemocyte populations
      differ considerably in their morphology, ultrastructure and lectin-binding
      properties. While oenocytoids are quite uniform with easily definable cells which
      do not to bind any assayed lectin, the plasmatocytes are a very polymorphic
      population possessing several morphological types and displaying a positive
      reactivity with lectins.

PMID- 9188176
TI  - Carbohydrate-binding specificities and physico-chemical properties of lectins in
      various tissue of phlebotominae sandflies.
AB  - Physico-chemical properties and carbohydrate-binding specificity of
      hemagglutination activity (HA) were compared in tissue lysates and haemolymph of
      unfed and bloodfed females of five sandfly species. Sandfly gut lectins were
      found to be heat-labile, sensitive to dithiotreitol treatment, freezing/thawing
      procedures and were affected by divalent cations. The pH optimum of HA ranged
      between 7.0-7.5. Specificity of gut HA of all species studied was directed
      towards aminosugars and some glycoconjugates, mainly lipopolysaccharide from
      Escherichia coli K-235, heparin and fetuin. Gut HA of Phlebotomus papatasi
      (Scopoli, 1786) was strongly inhibited by lipophosphoglycan (LPG) from Leishmania
      major promastigotes. In females, that took blood, the HA was higher but the
      carbohydrate-binding specificity remained the same; this suggests that the same
      lectin molecule was present, at different levels, both in unfed and fed flies.
      High HA was found in ovaries of fed females of Lutzomyia longipalpis (Lutz et
      Nieva, 1912), P. papatasi and P. duboscqi Neveu-Lemaire, 1906. In P. papatasi and
      P. duboscqi the HA was present also in the haemolymph and head lysates of both
      fed and unfed females. Carbohydrate-binding specificity of HA present in these
      tissues was similar with the gut lectin.

PMID- 9188177
TI  - Attempts to immunize chickens against Cryptosporidium baileyi with C. parvum
      oocysts and Paracox vaccine.
AB  - To study the possibility of immunization against Cryptosporidium baileyi Current,
      Upton et Haynes, 1986 with the attenuated anticoccidial vaccine, Paracox and
      oocysts of C. parvum Tyzzer, 1912, chickens were inoculated orally with either 3
      x 10(3) vaccine oocysts or 8 x 10(5) C. baileyi or C. parvum oocysts at 1 week of
      age. The inoculation with Paracox vaccine and C. parvum oocysts was repeated at 2
      and 3 weeks of age. Uninfected birds served as controls. All animals with the
      exception of one uninfected group were challenged orally with either 8 x 10(5) C.
      baileyi or 3 x 10(5) Eimeria tenella Railliet et Lucet, 1891 oocysts at 4 weeks
      of age. Sera were collected at 4 weeks of age, and were examined by ELISA using
      C. baileyi antigens. Birds inoculated with C. parvum oocysts did not shed C.
      parvum oocysts in their faeces, but anticryptosporidial antibodies could be
      detected in the sera. The total oocyst output of C. parvum inoculated chickens
      was 17% of that of previously uninfected birds after the oral challenge with C.
      baileyi. Considering that antibodies play no or only a minor role in resistance
      to C. baileyi, these results suggest that inoculation of chickens with C. parvum
      oocysts stimulated also cellular immune response. Based on the relative body
      weight gain, faecal scores, oocyst output, mortality, and caecal lesions in the
      birds immunized with Paracox vaccine and challenged with E. tenella, the
      vaccination induced only a moderate protection against the reinfection. The
      results of cross-immunization of chickens with Eimeria spp. and C. baileyi
      suggest that attenuated anti-eimerian vaccines do not induce any protection
      against cryptosporidial infection.

PMID- 9188178
TI  - Preparative enantiomer separation of the inhalation anesthetics enflurane,
      isoflurane and desflurane by gas chromatography on a derivatized gamma
      cyclodextrin stationary phase.
AB  - The preparative enantiomeric separation of the inhalation anesthetics enflurane
      (1) and isoflurane (2) in very high chemical (> 99.5%) and enantiomeric excess
      (ee > 99%) by gas chromatography (GC) on octakis(3-O-butanoyl-2,6-di-O-n-pentyl)
      gamma-cyclodextrin (4), dissolved in the apolar polysiloxane SE-54 and coated on
      Chromosorb P AW DMCS, is described. Up to 1 g of each enantiomer of 1-2 can been
      obtained per diem. The enantiomers of the highly volatile desflurane (3) can also
      be separated, albeit with diminished ee. The enantiomeric excess of 1-3 was
      checked by analytical GC on 4 and the absolute configuration of 2 and 3 has been
      determined via anomalous X-ray diffraction.

PMID- 9188179
TI  - Experimental and numerical studies of the chromatofocusing of dilute proteins
      using retained pH gradients formed on a strong-base anion-exchange column.
AB  - The separation of dilute protein mixtures was achieved using simple monovalent
      buffering species to form retained, internally produced pH gradients on a strong
      basic anion-exchange column. Highly focused proteins bands localized on stepwise
      pH transitions were produced experimentally under trace and volume overloaded
      feed conditions. Numerical simulations were performed that accurately predict the
      pH profile and protein band shapes in the column effluent. Experimental results
      were combined with numerical investigations to explore strategies for designing
      efficient preparative-scale chromatofocusing systems using simple, inexpensive
      buffers and adsorbents.

PMID- 9188180
TI  - Application of a beta-cyclodextrin sulfate-immobilized precolumn to selective on
      line enrichment and separation of heparin-binding proteins by column-switching
      high-performance liquid chromatography.
AB  - A column-switching high-performance liquid chromatography (HPLC) system which
      consisted of a beta-cyclodextrin (beta-CD) sulfate-immobilized hydrophilic vinyl
      polymer gel precolumn and a reversed-phase analytical column was developed for
      the selective on-line enrichment and separation of heparin-binding proteins. Of
      15 proteins investigated, 10 proteins having heparin-binding activity were
      retained on the beta-CD sulfate precolumn almost quantitatively, in contrast 5
      proteins having no heparin-binding activity were not retained. Calibration graphs
      for basic fibroblast growth factor constructed at various sample volumes were
      nearly identical, indicating that the protein could be enriched by this system.
      The system was successfully used for the selective separation of lysozyme in egg
      white. The beta-CD sulfate-immobilized precolumn showed no loss of analytical
      performance over 2 years during which about 400 samples were analysed.

PMID- 9188181
TI  - Enantioselectivity of bovine serum albumin-bonded columns produced with isolated
      protein fragments. II. Characterization of protein fragments and chiral binding
      sites.
AB  - Enantioselectivity of bovine serum albumin (BSA)-bonded columns produced with
      isolated protein fragments has been investigated. The BSA fragment, BSA-FG75, was
      isolated by size exclusion chromatography following peptic digest of BSA. The
      isolated BSA-FG75 was further fractionated to two fractions, BSA-F1 and BSA-F2,
      by anion-exchange chromatography. BSA-F1 and BSA-F2 had molecular mass of about
      35000 daltons, estimated by matrix-assisted laser desorption ionization time-of
      flight (MALDI-TOF) mass spectrometry, BSA-F1 has amino acid residues 1-307
      estimated by electrospray ionization (ESI) mass spectrometry, while BSA-F2 is an
      N-terminal half BSA fragment. The BSA, BSA-FG75, BSA-F1 and BSA-F2 proteins were
      bound to aminopropyl-silica gels activated by N,N'-disuccinimidyl carbonate. The
      bound amounts of the BSA fragments were 2.2-2.7 times more than that of the
      intact BSA. Chiral recognition of 2-arylpropionic acid derivatives,
      benzodiazepines, warfarin and benzoin was obtained with the BSA fragment-bonded
      columns. The non-enantioselective interactions of benzoin and benzodiazepines
      except for clorazepate with BSA fragments were increased with protein surface
      coverages, while those of 2-arylpropionic acid, clorazepate and warfarin were
      decreased. The BSA fragment columns gave higher enantioselectivity for lorazepam
      and benzoin, and lower enantioselectivity for other compounds tested, compared
      with the BSA column. These results might be due to changes in the globular
      structure of the BSA fragment and/or changes in the local environment around the
      binding sites.

PMID- 9188182
TI  - Simple and rapid chromatographic method for the separation of major classes of
      ribosomal ribomononucleotides.
AB  - We have described a simple and rapid chromatographic method for the analytical
      and preparative separation of major types of ribosomal ribomononucleotides with
      Dowex 1-X10 (HCOO-, 37-74 microns) and Dowex 2-X10 (HCOO-, 37-74 microns)
      columns, by desorption with formiate solutions in 1-2 h. The separation has been
      achieved for Cp, Ap, Up and Gp, while a mixture of 2'-, and 3'-nucleoside
      phosphates desorbs as a single peak; with both resins, a successful separation
      was achieved with a load from 25 micrograms to 1 mg of ribomononucleotide mixture
      per ml of packed resin. A complete separation was achieved with Dowex 1, while
      the separation with Dowex 2 resin was even better. The resins cannot separate
      unusual nucleosides; therefore, our method is suitable for studies of ribonucleic
      acids with a low content of unusual nucleosides. Our method has been applied for
      the quantitative determination of the ribomononucleotide composition of 18S and
      28S rRNAs, isolated from mammalian tissues: rat liver, mouse kidney and Ehrlich
      ascites cells. Dowex 1 and Dowex 2 resins afforded similar or identical
      ribomononucleotide compositions in all cases; analytical data were in agreement
      with the literature data. Our method is competitive, in several respects, with
      modern HPLC techniques for the separation of ribomononucleotides.

PMID- 9188183
TI  - Determination of the absolute configuration of sugar residues using gas
      chromatography. Method with potential for elimination of references.
AB  - The absolute configuration of a sugar can be determined by gas-liquid
      chromatography of the acetylated or trimethylsilylated dithioacetals from 1
      phenylethanethiol. The isolation of both enantiomers of 1-phenylethanethiol is
      also described. Using the acetates and both thiol reagents the absolute
      configuration of C-2 can be determined, provided it is a hydroxyl group, with
      great certainty. A new way of determining the absolute configuration of sugars,
      without references, is thereby provided. The sugars analysed include aldoses,
      deoxyaldoses, 2-acetamido-2-deoxyaldoses and uronic acids. The analysis is made
      using columns with non-chiral stationary phase and the electron impact mass
      spectra of the acetylated and trimethylsilylated bis(1-phenylethyl)dithioacetals
      are described.

PMID- 9188184
TI  - Simultaneous quantification of insecticides including carbaryl in drinking water
      by gas chromatography using dual electron-capture and nitrogen-phosphorus
      detection.
AB  - A rapid and simple gas chromatographic method for the simultaneous determination
      of malathion, parathion, fenitrothion, diazinon and carbaryl in drinking water is
      presented. A fused-silica SE-54 column was used for the separation of the
      insecticides and was split into two specific detectors; electron-capture and
      nitrogen-phosphorus detectors by using column switching. A water sample was
      extracted with methylene chloride. The organic phase was evaporated and the
      residue was derivatized with pentafluoropropionic acid anhydride. The detection
      limit was below 0.1 ng/ml and the calibration curves showed good linearity with r
      = 0.998 approximately 1.000. The method was sensitive, reproducible and simple
      enough to permit the reliable routine analysis of the pesticides in drinking
      water.

PMID- 9188185
TI  - Determination of cysteine by capillary zone electrophoresis with end-column
      amperometric detection at a gold/mercury amalgam microelectrode without
      deoxygenation.
AB  - Capillary zone electrophoresis was employed for the determination of cysteine
      using an end-column amperometric detection with a gold/mercury amalgam
      microelectrode, at a constant potential of 0.02-0.06 V vs. saturated calomel
      electrode. In this procedure deoxygenation is not necessary. The electrochemical
      characteristics at the microelectrode, the effect of the concentration of the
      buffer and the separation voltage across the capillary on the migration time and
      separation efficiency, and the dependence of the injection voltage and time on
      the detection signal, the separation efficiency and coulometric efficiency has
      been investigated. The calibration plot was found to be linear over four orders
      of magnitude and the limit of detection was 5.8 x 10(-8) mol/l (or 14.5 amol).
      The method was applied to the determination of cysteine in human plasma, blood
      and urine.

PMID- 9188186
TI  - Plant foods in the management of diabetes mellitus: vegetables as potential
      hypoglycaemic agents.
AB  - Vegetables are among the numerous plant adjuncts tried for the treatment of
      diabetes mellitus. A few vegetables that are commonly consumed in India have been
      claimed to possess antidiabetic potency. In recent years, there has been a
      renewed interest to screen such plant food materials, for a possible beneficial
      use. Considerable amount of work has been carried out in this regard with bitter
      gourd (Momordica charantia) and ivy gourd (Coccinia indica) both in experimental
      animals and human diabetic subjects. Majority of these studies have documented
      the beneficial effect of the fruit of bitter gourd and leaf of ivy gourd when
      administered orally as a single dose. The hypoglycaemic influence is claimed to
      be mediated through an insulin secretagogue effect or through an influence on
      enzymes involved in glucose metabolism. The limited number of studies on other
      vegetables such as cabbage (Brassica oleracia), green leafy vegetables, beans and
      tubers have shown the beneficial hypoglycaemic influence in both experimental
      animals and humans. There is scope for more extensive research in this area,
      especially to examine the long term beneficial effect of dietary vegetables, to
      identify the active principle, and to understand the mechanism of action, which
      is at present unclear. Since diet forms the mainstay in the management of
      diabetes mellitus, there is scope for exploiting the antidiabetic potency of
      vegetables to the maximum extent. Such plant food adjuncts possessing
      hypoglycaemic activity appear to hold promise as potential antidiabetic agents.

PMID- 9188187
TI  - Structural and functional changes of faba bean legumin during super-limited
      tryptic hydrolysis.
AB  - The influence of a super-limited tryptic hydrolysis on physicochemical and
      surface functional properties of faba bean legumin has been studied using size
      exclusion HPLC, SDS-PAGE, UV and fluorescence spectroscopy, fluorescence probe
      techniques, surface tension measurements as well as determination of emulsifying
      activity index (EAI) and emulsion droplets diameter (D). The extent of legumin
      hydrolysis comprised the range between about 14 and 60 split peptide bonds per
      molecule resulting in a stepwise decrease of legumin molecular weight to 240 kDa
      (legumin-T) via discrete intermediates with characteristic subunit patterns.
      These changes are accompanied by an increase in the surface hydrophobicity and
      the exposure of aromatic chromophores. No differences were found in the surface
      tension between the variously hydrolyzed legumin samples. Best emulsifying
      properties (highest EAI and lowest D values) were attained after a rather low
      tryptic hydrolysis (about 30 split peptide bonds per mol). Further hydrolysis
      impaired the emulsifying parameter which were, however, higher (EAI) or lower (D)
      than those for native legumin.

PMID- 9188188
TI  - Evidence for peptide synthesis in the course of in vitro proteolysis.
AB  - The present paper reports on studies concerned with furnishing evidence for
      peptide synthesis in the course of in vitro proteolysis. To this end, the
      oxidized chain B from insulin (INS) (S = 5% in demineralized water) was subjected
      to tryptic proteolysis (E/S = 1/50; pH 5; 37 degrees C; 24 h). HPLC-as well as
      amino acid-and sequence analytical studies have shown that the heptapeptide INS
      23-29 (Gly-Phe-Phe-Tyr-Thr-Pro-Lys) liberated by way of hydrolysis is linked by
      tryptic synthesis via transpeptidation or condensation to form a dimer which
      accounts for 15% of the amount of monomer. The results of the model trials show
      clearly that during in vitro proteolysis chemical reactions beyond hydrolytic
      cleavage of peptide bonds take place. In principle, plastein-like reactions
      (transpeptidation, condensation) can occur during each in vitro proteolysis.

PMID- 9188189
TI  - Study of chromium and nickel content in white asparagus (Asparagus officinalis,
      L.).
AB  - The modifications in the chromium (Cr) and nickel (Ni) content and the
      distribution of these trace elements in white asparagus spears (Asparagus
      officinalis, L.) were investigated. Samples were taken of two varieties of white
      asparagus, Desto and Cipres, and grouped in function of their thickness in spears
      of < 11 mm and of > 14 mm. All the asparagus samples were cut in lengths of 20 cm
      and divided into 10 portions of 2 cm each. The determinations of chromium and
      nickel were carried out by atomic absorption spectrophotometry with air-acetylene
      flame. The mean concentrations were 0.675 +/- 0.19 and 5.578 +/- 1.39 mg/kg dry
      weight for chromium and nickel, respectively. By means of three-factor analyses
      of variance (varieties, thickness and portions), statistically significant
      differences were determined between the concentrations of chromium and nickel and
      each one of the sources of variation established. The chromium content showed a
      variable distribution throughout the white asparagus portions as a result of the
      notable differences between varieties and thickness. In the case of nickel, its
      levels underwent a generalized decrease as the spear portions were further and
      further away from the apical area or tip of the white asparagus.

PMID- 9188190
TI  - Physiological gain leads to high ISI variability in a simple model of a cortical
      regular spiking cell.
AB  - To understand the interspike interval (ISI) variability displayed by visual
      cortical neurons (Softky & Koch, 1993), it is critical to examine the dynamics of
      their neuronal integration, as well as the variability in their synaptic input
      current. Most previous models have focused on the latter factor. We match a
      simple integrate-and-fire model to the experimentally measured integrative
      properties of cortical regular spiking cells (McCormick, Connors, Lighthall, &
      Prince, 1985). After setting RC parameters, the post-spike voltage reset is set
      to match experimental measurements of neuronal gain (obtained from in vitro plots
      of firing frequency versus injected current). Examination of the resulting model
      leads to an intuitive picture of neuronal integration that unifies the seemingly
      contradictory 1/square root of N and random walk pictures that have previously
      been proposed. When ISIs are dominated by postspike recovery, 1/square root of N
      arguments hold and spiking is regular; after the "memory" of the last spike
      becomes negligible, spike threshold crossing is caused by input variance around a
      steady state and spiking is Poisson. In integrate-and-fire neurons matched to
      cortical cell physiology, steady-state behavior is predominant, and ISIs are
      highly variable at all physiological firing rates and for a wide range of
      inhibitory and excitatory inputs.

PMID- 9188191
TI  - Shunting inhibition does not have a divisive effect on firing rates.
AB  - Shunting inhibition, a conductance increase with a reversal potential close to
      the resting potential of the cell, has been shown to have a divisive effect on
      subthreshold excitatory postsynaptic potential amplitudes. It has therefore been
      assumed to have the same divisive effect on firing rates. We show that shunting
      inhibition actually has a subtractive effect on the firing rate in most
      circumstances. Averaged over several interspike intervals, the spiking mechanism
      effectively clamps the somatic membrane potential to a value significantly above
      the resting potential, so that the current through the shunting conductance is
      approximately independent of the firing rate. This leads to a subtractive rather
      than a divisive effect. In addition, at distal synapses, shunting inhibition will
      also have an approximately subtractive effect if the excitatory conductance is
      not small compared to the inhibitory conductance. Therefore regulating a cell's
      passive membrane conductance-for instance, via massive feedback-is not an
      adequate mechanism for normalizing or scaling its output.

PMID- 9188192
TI  - Paradigmatic working memory (attractor) cell in IT cortex.
AB  - We discuss paradigmatic properties of the activity of single cells comprising an
      attractor-a developed stable delay activity distribution. To demonstrate these
      properties and a methodology for measuring their values, we present a detailed
      account of the spike activity recorded from a single cell in the inferotemporal
      cortex of a monkey performing a delayed match-to-sample (DMS) task of visual
      images. In particular, we discuss and exemplify (1) the relation between
      spontaneous activity and activity immediately preceding the first stimulus in
      each trial during a series of DMS trials, (2) the effect on the visual response
      (i.e., activity during stimulation) of stimulus degradation (moving in the space
      of IT afferents), (3) the behavior of the delay activity (i.e., activity
      following visual stimulation) under stimulus degradation (attractor dynamics and
      the basin of attraction), and (4) the propagation of information between trials
      the vehicle for the formation of (contextual) correlations by learning a fixed
      stimulus sequence (Miyashita, 1988). In the process of the discussion and
      demonstration, we expose effective tools for the identification and
      characterization of attractor dynamics.

PMID- 9188193
TI  - Aerobic degradation of polychlorinated biphenyls by Alcaligenes sp. JB1:
      metabolites and enzymes.
AB  - In contrast to the degradation of penta- and hexachlorobiphenyls in chemostat
      cultures, the metabolism of PCBs by Alcaligenes sp. JB1 was shown to be
      restricted to PCBs with up to four chlorine substituents in resting-cell assays.
      Among these, the PCB congeners containing ortho chlorine substituents on both
      phenyl rings were found to be least degraded. Monochloro-benzoates and
      dichlorobenzoates were detected as metabolites. Resting cell assays with
      chlorobenzoates showed that JB1 could metabolize all three monochlorobenzoates
      and dichlorobenzoates containing only meta and para chlorine substituents, but
      not dichlorobenzoates possessing an ortho chlorine substituent. In enzyme
      activity assays, meta cleaving 2,3-dihydroxybiphenyl 1,2-dioxygenase and catechol
      2,3-dioxygenase activities were constitutive, whereas benzoate dioxygenase and
      ortho cleaving catechol 1,2-dioxygenase activities were induced by their
      substrates. No activity was found for pyrocatechase II, the enzyme that is
      specific for chlorocatechols. The data suggest that complete mineralization of
      PCBs with three or more chlorine substituents by Alcaligenes sp. JB1 is unlikely.

PMID- 9188194
TI  - Cultivation of Escherichia coli with mixtures of 3-phenylpropionic acid and
      glucose: dynamics of growth and substrate consumption.
AB  - In technical as well as natural ecosystems, pollutants are often mineralised in
      the presence of easily degradable carbon sources. A laboratory model system
      consisting of Escherichia coli ML 30 growing with mixtures of 3-phenylpropionic
      acid (3ppa, 'pollutant') and glucose (easily degradable substrate) was
      investigated in batch and carbon-limited continuous culture. Untypically, a
      linear growth pattern was observed during batch cultivation with 3ppa as the only
      carbon/energy source. When exposed to mixtures of both substrates in batch
      culture, E. coli utilised the two compounds sequentially. However, 3ppa and
      glucose were consumed simultaneously in continuous culture. Whereas a pulse of
      excess glucose to a batch culture growing with 3ppa led to the repression of 3ppa
      utilisation, an excess of glucose added into continuous culture did not inhibit
      the utilisation of 3ppa. During continuous cultivation the 3ppa-degrading enzyme
      system operated close to saturation.

PMID- 9188195
TI  - Biodegradation of the mixtures of 4-chlorophenol and phenol by Comamonas
      testosteroni CPW301.
AB  - A 4-chlorophenol (4-CP)-degrading bacterium, strain CPW301, was isolated from
      soil and identified as Comamonas testosteroni. This strain dechlorinated and
      degraded 4-CP via a meta-cleavage pathway. CPW301 could also utilize phenol as a
      carbon and energy source without the accumulation of any metabolites via the same
      meta-cleavage pathway. When phenol was added as an additional substrate, CPW301
      could degrade 4-CP and phenol simultaneously. The addition of phenol greatly
      accelerated the degradation of 4-CP due to the increased cell mass. The
      simultaneous degradation of the 4-CP and phenol is useful not only for enhanced
      cell growth but also for the bioremediation of both compounds, which are normally
      present in hazardous waste sites as a mixture.

PMID- 9188196
TI  - Degradation of bis(2-ethylhexyl) phthalate constituents under methanogenic
      conditions.
AB  - The degradation of bis(2-ethylhexyl) phthalate (DEHP) and its intermediary
      hydrolysis products 2-ethylhexanol (2-EH) and mono(2-ethylhexyl) phthalate (MEHP)
      was investigated in a methanogenic phthalic acid ester-degrading enrichment
      culture at 37 degrees C. 2-Ethylhexanoic acid (2-EHA), a plausible degradation
      product of 2-EH, was also studied. The culture readily degraded 2-EH via 2-EHA to
      methane which was formed in stoichiometric amounts assuming complete degradation
      of 2-EH to methane and carbon dioxide. MEHP was degraded to stoichiometric
      amounts of methane with phthalic acid as a transient intermediate. DEHP remained
      unaffected throughout the experimental period (330 days).

PMID- 9188197
TI  - Isolation of an anaerobic bacterium which reductively dechlorinates
      tetrachloroethene and trichloroethene.
AB  - Strain TEA, a strictly anaerobic, motile rod with one to four lateral flagella
      and a crystalline surface layer was isolated from a mixed culture that completely
      reduces chlorinated ethenes to ethene. The organism coupled reductive
      dehalogenation of tetrachloroethene or trichloroethene to cis-1,2-dichloroethene
      to growth, using molecular hydrogen as the electron donor. It was unable to grow
      fermentatively or in the presence of tri- or tetrachloroethene with glucose,
      pyruvate, lactate, acetate or formate. The 16S rDNA sequence of strain TEA was
      99.7% identical to that of Dehalobacter restrictus. The two organisms thus are
      representatives of the same species or the same genus within the
      Bacillus/Clostridium subphylum of the gram-positive bacteria.

PMID- 9188198
TI  - Regulation of a continuous yeast bioreactor near the critical dilution rate using
      a productostat.
AB  - Regulation of a continuous bioreactor with Saccharomyces cerevisiae is
      investigated. A number of different sensors are evaluated for this purpose and
      the process dynamics is investigated around the critical dilution rate. A sensor
      for reducing gas concentration in exhaust gases is selected for regulating the
      substrate flow rate. Closed loop identification experiments are carried out to
      enable identification of the process dynamics near the critical diluton rate. Due
      to the time-varying nature of this process an adaptive regulator seems to be a
      promising tool for providing good regulatory and setpoint tracking performance. A
      simple third order model is used for a model based control design with a Linear
      Quadratic (LQ)-regulator. The LQ-regulator performs well experimentally, both in
      an adaptive version where the model parameters are updated on-line, and in a non
      adaptive version. During the test the process is exposed to a large disturbance
      in substrate feed concentration and to a small setpoint disturbance. The proposed
      regulator is a practical realisation of a productostat where the product in this
      case is an undesired primary metabolite. Thus, this paper demonstrates a more
      general principle of utilizing metabolic overflow metabolism for directing fluxes
      through a desired metabolic pathway. This principle is applicable in the
      presented form, if a (by-)product can be measured on-line.

PMID- 9188199
TI  - Production of human interleukin-8 expressed in Escherichia coli: from a
      laboratory scale for in vitro tests via a technical scale for animal studies to a
      process scale for a GMP-compatible production.
AB  - An Escherichia coli K 12 strain has been constructed for efficient expression of
      recombinant biologically active human IL-8 (Interleukin-8). The development of a
      fermentation and purification process from the laboratory scale (cells from 15 l
      fermentation broth) to a production scale (cells from 200 l fermentation broth)
      is described. Material obtained from the laboratory scale was used for initial in
      vitro studies and for the development of a biological assay. An upscale
      purification process starting from 80 l fermentation broth resulted in larger
      amounts of IL-8 needed for preclinical studies. This process includes a fully
      automated control of the initial affinity chromatography step. Finally, a
      production process which differed markedly from the small-scale processes was
      tailor-made for GMP conformity and economic considerations. It consists of a cell
      disruption step followed by two crossflow diafiltrations with different molecular
      weight cut offs and filtration rates, one cation exchange chromatography and a
      final dialysis step. In order to enhance the overall yield of biologically active
      IL-8, conditions for a resolubilisation of insoluble IL-8 present in the
      remaining pellet after cell disruption were worked out.

PMID- 9188200
TI  - Characterisation of non-porous magnetic chelator supports and their use to
      recover polyhistidine-tailed T4 lysozyme from a crude E. coli extract.
AB  - The use of high capacity micron-sized non-porous magnetic metal chelator
      adsorbents for the direct recovery of a recombinant metal-binding protein from
      crude liquors is described. Selectivity and interaction strength of magnetic
      chelator particles were assessed using a set of native proteins with known
      behaviour towards commercially available immobilised metal chelate adsorbents.
      Particles charged with Cu2+ were highly effective in recovering a recombinant
      histidine-tailed T4 lysozyme fusion protein directly from crude E. coli extracts
      in a single step. Levels of recovery and purity were high and compared favourably
      with those achieved by chromatography of pre-clarified extracts on Cu(2+)-IDA
      Sepharose. The magnetic approach offers advantages such as the avoidance of
      clarification to prevent fouling of chromatography columns, steps that become
      especially significant at large scale. By detailed characterisation of the
      magnetic chelators the practical use of tailed T4 lysozyme for repeated
      production of periplasmic products is a realistic prospect.

PMID- 9188201
TI  - Cloning, sequencing and overexpression of the leucine dehydrogenase gene from
      Bacillus cereus.
AB  - The L-leucine dehydrogenase gene from Bacillus cereus (DSM 626) was cloned from a
      partial genomic library and sequenced. The open reading frame has 1101 bp and
      codes for a protein of 39.9 kDa. The deduced amino acid sequence of the LeuDH
      from B. cereus shares 70-80% identity with LeuDH's from the thermophilic strains
      B. stearothermophilus and Thermoactinomyces intermedius. The active protein was
      overexpressed in Escherichia coli to yield approximately 30% of the total soluble
      protein.

PMID- 9188202
TI  - Dangers of low-dose corticosteroid therapy in rheumatoid arthritis.
AB  - Corticosteroids, even in low doses, have substantial side effects. In addition,
      once they are instituted for RA it is unlikely that they will ever be stopped.
      Therefore, the decision to employ this therapy requires careful thought by the
      physician and informed consent from the patient.

PMID- 9188204
TI  - Myocardial aspects of HIV infection.

PMID- 9188203
TI  - Benefits of low-dose corticosteroids in rheumatoid arthritis.

PMID- 9188205
TI  - Towards an understanding of the molecular pathogenesis of acute coronary
      syndromes.

PMID- 9188206
TI  - On the mechanism(s) of atrioventricular nodal transmission in atrial
      fibrillation.

PMID- 9188207
TI  - Effects of A1 adenosine receptor blockade on the warm-up phenomenon.
AB  - The increased tolerance to myocardial ischemia observed during the second of two
      sequential exercise tests, i.e. the warm-up phenomenon, has been proposed as a
      clinical model of ischemic preconditioning. Adenosine appears to be a mediator of
      ischemic preconditioning in both experimental and clinical settings. The purpose
      of this study was to investigate the role of A1 adenosine receptors in the warm
      up phenomenon. A double-blind, placebo-controlled, cross-over design was used.
      Twelve patients with coronary artery disease and positive exercise test were
      randomized to receive either bamiphylline, a selective A1 adenosine receptor
      antagonist, or placebo, immediately prior to two consecutive treadmill exercise
      tests carried out on day 1. Then, on day 2 all patients underwent two consecutive
      exercise tests immediately after administration of the remaining treatment.
      During the first exercise test, bamiphylline, compared to placebo, increased the
      time to and rate-pressure product at 1.5 mm ST-segment depression (from 317 +/-
      118 to 423 +/- 127 s, p < 0.05 and from 199 +/- 38 to 230 +/- 36
      b/min.mmHg.10(2), p < 0.05, respectively). After both placebo and bamiphylline
      infusions, time to 1.5 mm ST-segment depression during the second exercise test
      was greater than that during the first test (445 +/- 121 vs 317 +/- 118 s, p <
      0.001 and 483 +/- 128 vs 423 +/- 127 s, p < 0.05, respectively), as was rate
      pressure product at 1.5 mm ST-segment depression (228 +/- 40 vs 199 +/- 38
      b/min.mmHg.10(2), p < 0.01 and 253 +/- 42 vs 230 +/- 36 b/min.mmHg.10(2), p <
      0.05, respectively). In conclusion, bamiphylline, at a dose able to increase
      ischemic threshold and exercise tolerance compared to placebo, does not prevent
      the warm-up phenomenon. These findings suggest that, in the setting of the warm
      up phenomenon, A1 adenosine receptor blockade is insufficient to prevent ischemic
      preconditioning.

PMID- 9188208
TI  - Evaluating adrenal incidentalomas.

PMID- 9188209
TI  - A 30-year-old woman with headache.

PMID- 9188210
TI  - Cyclospora: update on an emerging pathogen.
AB  - Cyclospora cayetanensis, an emerging pathogen with worldwide distribution, causes
      diarrhea in both immunocompetent and HIV-infected patients. We review the
      epidemiology of Cyclospora infection and how to diagnose and treat it.

PMID- 9188211
TI  - Building-related illness and sick building syndrome: from the specific to the
      vague.
AB  - When a primary-care physician encounters a patient with a possible building
      related illness, common sense applies. Does the patient have a potentially
      serious condition? Does he or she need a referral to a specialist? This paper
      explores the topics of building-related illness and sick building syndrome.

PMID- 9188212
TI  - Adult vaccinations: a short review.
AB  - Rates of vaccination in adults fall far short of recommendations. We review the
      epidemiology, efficacy, safety, and recommended use of vaccines against
      pneumococcal pneumonia, influenza, hepatitis A and B, varicella, measles, mumps,
      rubella, tetanus, and diphtheria.

PMID- 9188213
TI  - Detecting and preventing ventricular remodeling after MI.
AB  - Infarct expansion carries a poor prognosis. Echocardiography can identify this
      condition by identifying distortion of the ventricular topography. In this review
      we discuss the acute and long-term effects of thrombolysis on infarct expansion
      and subsequent left ventricular remodeling after acute myocardial infarction.

PMID- 9188214
TI  - Cosmetic use of alpha-hydroxy acids.
AB  - Frequent and daily use of cosmetic and skin-care products that contain alpha
      hydroxy acids (AHAs) moisturizes the skin and produces smoother, less-wrinkled
      skin surfaces. The cosmetic products developed as astringents and exfoliants
      diminish skin scales and remove excess skin oil. New studies suggest that
      photodamaged skin improves with AHA treatment.

PMID- 9188215
TI  - The shifting etiologies of lobar hemorrhage.

PMID- 9188216
TI  - What primary care physicians should know about the toxicity of cancer
      chemotherapy.

PMID- 9188217
TI  - Surveillance of progressive intellectual and neurological deterioration in
      children.

PMID- 9188218
TI  - Pertussis notifications in Australia, 1991 to 1997.
AB  - Although pertussis is a vaccine-preventable disease, it has been epidemic in
      Australia since 1993 and recently claimed the lives of four children under three
      months of age. We reviewed national notifications of pertussis from 1991 to 1997
      and found notification rates ranged from 2.0 per 100,000 population in 1991 to a
      peak of 30.5 per 100,000 population in 1994 despite pertussis vaccination
      coverage approaching 90% for the three-dose primary course. We found that
      notification rates were highest in infants (< 1 year of age) and school aged
      children (5-14 years of age). Although there was a resurgence of pertussis in
      1996, age-specific notification rates decreased for children aged 1-7 years and
      it appears that the diphtheria-tetanus-pertussis (DTP) booster introduced as a
      fifth dose at 4-5 years may be having an effect. We raise the possibility that
      the current whole cell pertussis vaccine may be providing only short-term
      immunity and that our results may reflect low or inadequate vaccine coverage
      among both the population at large and the individual cases. We identify gaps in
      the national surveillance system which require attention including under
      reporting and the need for information on vaccination status of notified cases;
      method of diagnosis; and date of birth or age in months to identify the
      proportion of infants in the highest risk group, that is under six months of age.

PMID- 9188219
TI  - Communicable diseases surveillance.

PMID- 9188220
TI  - Physician-assisted dying: the coming debate.

PMID- 9188221
TI  - Multi-center sestamibi parathyroid imaging study in Hawaii.
AB  - Technetium-99m (99mTc) sestamibi (MIBI) was first used as a parathyroid imaging
      agent in Hawaii in 1991. The purpose of this study was to determine the
      sensitivity and positive predictive value of the MIBI scan in detecting abnormal
      parathyroid glands. A retrospective, multi-center study from 1992-1994 involving
      33 patients in four hospitals showed the overall sensitivity of the MIBI scan for
      detecting hyperparathyroid disease was 90%. The positive predictive value was
      93%. It was more sensitive in detecting adenomas (95%) than hyperplasia (45%). In
      conclusion, the MIBI scan can be helpful in detecting abnormal parathyroid glands
      and may be most useful prior to reoperations for persistent and recurrent
      hyperparathyroidism.

PMID- 9188222
TI  - "KITS" for improved immunization of Kauai children.
AB  - Kauai physicians and District Health Office staff established a computerized
      tracking system in 1993 to improve immunization rates in Kauai-born infants.
      Comparison of 1995 and 1996 audit results of 1993- and 1994-born children showed
      completion rates for 9 antigens rose from 76% to 86%. Evolution and improvement
      of the tracking system are discussed. Recommendations for physicians are offered.

PMID- 9188223
TI  - What do dentists do when they don't do dentistry?

PMID- 9188224
TI  - Cracked-tooth syndrome.

PMID- 9188225
TI  - Nitrous oxide.

PMID- 9188226
TI  - Crohn's disease revisited.

PMID- 9188227
TI  - Nonrestorative treatment of discolored teeth: reports from an International
      Symposium.

PMID- 9188228
TI  - Evidence-based periodontal treatment. Highlights from the 1996 World Workshop in
      Periodontics.
AB  - State-of-the-art periodontal therapy involves a wide range of diagnostic and
      treatment options. The 1996 World Workshop in Periodontics used an evidence-based
      approach to assess the efficacy of many of these options. This article describes
      the evidence-based approach and summarizes the findings of the workshop in the
      areas of diagnosis and nonsurgical and surgical periodontal therapy as well as
      dental implants.

PMID- 9188229
TI  - Effect of 10 percent carbamide peroxide on color of provisional restoration
      materials.
AB  - To improve esthetic results, nightguard vital bleaching of teeth using 10 percent
      carbamide peroxide, or CP, may be indicated when an anterior tooth is restored
      with a provisional crown. This study evaluated the effect of NGVB solutions
      containing 10 percent CP on the color stability of provisional restoration
      materials. Disks were fabricated from six representative provisional restoration
      materials and were tested in five different 10 percent CP bleaching agents. An
      orange discoloration occurred with provisional materials that contained
      methacrylate when they were exposed to 10 percent CP bleaching solutions.

PMID- 9188230
TI  - Comparing the tensile strength of brackets adhered to laser-etched enamel vs.
      acid-etched enamel.
AB  - This study compared the tensile bond strength of brackets adhered to laser-etched
      enamel with that of brackets adhered to acid-etched enamel. Forty extracted,
      intact bovine teeth were treated with either 37 percent phosphoric acid for 15
      seconds or neodymium:yttrium-aluminumgarnet laser on black-ink-coated enamel.
      After thermocycling, tensile stress was applied to the bonded specimens at a 0.1
      millimeter/minute orosshead speed. A t-test comparison of means showed a
      significant difference between the laser-etched and acid-etched teeth, with the
      acid-etched teeth demonstrating significantly more tensile bond strength at a 95
      percent level of significance.

PMID- 9188231
TI  - Identifying undiagnosed rheumatic disorders among patients with TMD.
AB  - If a patient with TMD has a coexisting rheumatic disorder, it may adversely
      affect the TMD symptoms and treatment outcome. A clinic that specializes in TMD
      treatment asked symptom-related questions of 104 patients with TMD, and a
      rheumatology clinic then performed rheumatologic evaluations. The authors review
      the results of the rheumatologic evaluations and the predictive probability for
      the questions. The findings of this study suggest questions that practitioners
      can ask to help identify patients with TMD who have a high probability of being
      diagnosed with a coexisting rheumatic disorder.

PMID- 9188232
TI  - Pseudocysts of the mandibular condyle in children.
AB  - The authors evaluated the panoramic radiographs of 1,193 consecutively treated
      patients 18 years old and younger for the presence of asymptomatic radiolucencies
      in the mandibular condyles. The 27 radiographs initially selected were examined
      by four independent reviewers. Of the 1,193 patients, 18 (1.5 percent [10 female
      and eight male]) met the criteria for condylar pseudocysts. Follow-up radiographs
      showed minimal or no change in size of the radiolucencies. Clinicians need to be
      aware of these anatomic variations so that patients are not subjected to
      inappropriate treatment.

PMID- 9188233
TI  - Forceps extraction of teeth with severe internal root resorption.
AB  - Many treatment plans require a dental practitioner to maintain the entire labial
      cortical plate of bone when removing an anterior maxillary tooth. A tooth with an
      undermined root secondary to an endodontic perforation or internal (Idiopathic)
      resorption can present a surgical challenge to the general practitioner. This
      article describes a new technique for extracting a severely undermined anterior
      maxillary tooth while maintaining the entire labial cortex of bone.

PMID- 9188234
TI  - A new approach to at-home oral irrigation.

PMID- 9188235
TI  - Four dimensions of fear of dental injections.
AB  - In 1995, students and staff at the University of Washington were surveyed
      regarding avoidance of dental care and fear of dental injections. More than 25
      percent of adults surveyed expressed at least one clinically significant fear of
      injections. Almost one in 20 respondents indicated avoiding, cancelling or not
      appearing for dental appointments because of fear of dental injections. Fear of
      dental injections consists of four dimensions. General fear of dental injections
      including pain of injection and of bodily injury from injection are the two most
      common dimensions of dental injection fear. Many people also express fears of
      acquired disease. Fear related to local anesthetic (such as side effects,
      inadequate anesthesia) is less frequent. Some respondents have fears that must be
      categorized using more than one of these dimensions. Understanding the nature of
      a patient's fear of injection may suggest strategies to address his or her
      concerns.

PMID- 9188236
TI  - Restoration or crown?

PMID- 9188237
TI  - First encounters: transmission of infectious oral diseases from mother to child.

PMID- 9188238
TI  - ECG of the month. Magic bullet? Narrow-QRS tachycardia.

PMID- 9188239
TI  - Carcinoma of the buccal mucosa: a 30-year analysis at the Medical Center of
      Louisiana at New Orleans.
AB  - Carcinoma of the buccal mucosa is an uncommon malignancy of the oral cavity which
      is primarily squamous cell in histologic origin. This study represents the first
      investigation of this lesion in an indigent population. The purpose of this
      report is to review survival rates, modalities of treatment, and current
      management of the disease. A retrospective analysis is performed on all patients
      with this disease diagnosed and treated from 1965 to 1995. Of 28 patients, 75%
      were white, advanced stages of disease predominated, and no 5-year Stage IV
      survivors were recorded. Additional conclusions of this study revealed an overall
      5-year determinate survival rate which was lower than other studies (25%), with a
      statistically significant white predominance of disease.

PMID- 9188240
TI  - Radiology case of the month. Hip trauma. Normal physiologic asymmetric closure of
      the ischiopubic synchondroses.

PMID- 9188241
TI  - The journal 100 & 150 years ago. Bizarre deaths and diseases of American
      Presidents. Part II.

PMID- 9188242
TI  - Firearm injury in Orleans parish: a 24-month perspective.
AB  - This study is a retrospective review of all gunshot wounds treated at Charity
      Hospital, the Orleans Parish designated trauma center, for the 24-month period
      from November 1993 to November 1995. Its purpose was to define the magnitude of
      firearm injury in the parish and the impact on the health care system. One
      thousand-six-hundred-sixty-nine gunshot wounds were analyzed. Most involved
      African-American males. Twenty percent were fatal. Two-thousand-forty-three
      emergent operations were performed. Ten percent of surviving patients had some
      permanent disability, 6% required institutional care. In 760 patients, initial
      hospital charges totaled $5,153,516. Extrapolation of these figures to the entire
      group yields an initial hospital cost of $11,317,392. Transport by the "911"
      system and in-house trauma team activation were required in most patients. In
      summary, firearm injury poses a serious economic problem and is a substantial
      drain on health care providers and their resources.

PMID- 9188243
TI  - St. Thomas Immunization Initiative. A student-run community action project.
AB  - The objectives of the St Thomas Immunization Initiative are to provide a clinical
      community medicine experience for first- and second-year medical students, expose
      students to a community immunization program, teach students the principles of a
      community immunization program, and demonstrate a working relationship between
      the residents of an underserved community and medical students. From 1993 to
      1995, first- and second-year students at Tulane University Medical School
      participated in class projects known as Shots for Tots and the St Thomas
      Immunization Initiative. Students received instruction about immunizations and
      administered vaccinations to children and adults in low-income neighborhoods. A
      total of 754 immunizations were administered to 331 children from 1993 to 1995.
      Participating students were surveyed and 82% of those who responded to a
      questionnaire felt that the project benefited the community it served while 79%
      felt that they personally benefitted from participating in the project. Given
      their experience, 96% of the students would be more likely to participate in a
      community development project in the future.

PMID- 9188244
TI  - An analysis of the actual cost of tibial nonunions.
AB  - The financial and medical records of 11 patients diagnosed with a tibial nonunion
      were evaluated in order to assess the costs associated with the care of this
      clinical entity. The initial tibia fractures were seen at Hermann Hospital
      (Houston, Texas) between April 1991 and June 1993. We included only those
      patients who had a diagnosis of tibial shaft nonunion which we defined as a
      tibial fracture which was without radiographic or clinical evidence of
      progressive healing 6 months after the initial injury. A total of 9 patients were
      available for evaluation and 2 were lost to follow-up.

PMID- 9188245
TI  - An expert systems approach to medical school admissions.
AB  - Medical school applicants for 1994 to 1995 broke the record of 42,621 applicants
      set in 1974 to 1975 with a new record of 45,365 applicants. Applications for the
      next few years are projected to steadily increase. Currently most medical school
      admissions committees screen every application. With the rising numbers of
      applications received each year, this task will soon be unfeasible. Our goal was
      to develop a computer-based expert system with high sensitivity that could be
      used as a preliminary screening tool for applications. A screening tool with high
      sensitivity should allow well-qualified and borderline candidates to go on to be
      fully evaluated by the admissions committee. This article is a report of the
      program developed, the attributes used, their assigned values, case scenarios,
      and suggestions for further uses.

PMID- 9188247
TI  - Prevention, diagnosis and treatment of viral hepatitis.

PMID- 9188246
TI  - The role of modified food starches in baby food.
AB  - Modified food starches were developed as a stabilizer, suspending the food
      particles and providing a desirable consistency, texture, and storage ability.
      They are used primarily in strained and junior foods and to a minor extent in
      infant formulas. This review discusses modified food starches because of four
      principal concerns. The first relates to the bioavailability of the starch
      itself. The second is the potential that indigestible starch may have for
      producing diarrheal symptoms, malabsorption, and changes in gastrointestinal
      flora. The third is the possibility that modified food starches might be
      implicated in gastrointestinal disease like Crohn's ileocolitis. The fourth is
      the toxicological effect of the chemicals used to modify the starch and their
      possible mutagenic and carcinogenic properties.

PMID- 9188249
TI  - So long to Medicaid peer review.

PMID- 9188248
TI  - Common afflictions of the hand.

PMID- 9188250
TI  - Dentistry presents a common thread.

PMID- 9188251
TI  - Round two: dentist victorious in AIDS discrimination case.

PMID- 9188252
TI  - Medical Liability Mutual Insurance Co. responds to malpractice series. Vice
      president assures policyholders their interests will be represented.

PMID- 9188253
TI  - Not fit to print.

PMID- 9188254
TI  - Where's the proof?

PMID- 9188255
TI  - Well done.

PMID- 9188256
TI  - Let me be the judge.

PMID- 9188257
TI  - A circus atmosphere.

PMID- 9188258
TI  - Time warp.

PMID- 9188259
TI  - Editor should step down.

PMID- 9188260
TI  - Animals have no choice.

PMID- 9188261
TI  - Ethics in a professional life.

PMID- 9188262
TI  - Transient diplopia as a result of block injections. Mandibular and posterior
      superior alveolar.
AB  - Anesthetic "accidents" can and do happen as a result of maxillary and/or
      mandibular injections. The family practitioner has little or no control now. The
      anatomical pathways are discussed, but are not clear.

PMID- 9188263
TI  - Treatment of gingival Crohn's disease with laser therapy.
AB  - Crohn's disease is an inflammatory disease of unknown etiology. Oral
      manifestations appear most frequently on the lips, gingival tissue and buccal
      mucosa. The case presented here shows how a patient with oral lesions resulting
      from Crohn's disease can be treated by laser therapy and obtain optimal esthetic
      results.

PMID- 9188264
TI  - Childhood hypophosphatasia. A case report.
AB  - Hypophosphatasia is a hereditary disease that can present as premature
      exfoliation of deciduous dentition in young children. We present a case of a 32
      month-old female with a history of skeletal problems who spontaneously exfoliated
      three mandibular primary teeth. It was the premature exfoliation of her
      mandibular teeth that led to the diagnosis of childhood hypophosphatasia.

PMID- 9188265
TI  - ADA takes stand on at-home bleaching products.

PMID- 9188266
TI  - Nursing presence: an existential exploration of the concept.
AB  - Nursing presence emerged in the nursing literature in the 1960s as a coherent and
      consistent philosophical term based in the existentialism of Gabriel Marcel and
      Martin Heidegger, and the religious philosophy of Martin Buber. Since the mid
      1980s, however, the precision in definition has deteriorated and presence has
      accrued multiple meanings, resulting in a weakened sense of the concept. After
      delineating the etymological and philosophical foundations of nursing presence,
      the concept is defined. The existential nature of nursing presence is explored
      and arguments for the indispensability of nursing presence are offered to counter
      the claims of bottom-line thinking. A definition is offered of nursing presence
      as an intersubjective encounter between a nurse and a patient in which the nurse
      encounters the patient as a unique human being in a unique situation and chooses
      to "spend" herself on his behalf.

PMID- 9188268
TI  - Bandura's theory of self-efficacy: applications to oncology.
AB  - Self-efficacy (Bandura, 1986) has been shown to impact on health practices as
      well as adaptation to illness and treatment. The purposes of this paper are to
      describe self-efficacy theory and review literature using self-efficacy theory to
      investigate prevention of cancer and adaptation to cancer. Measurement of self
      efficacy is also discussed. Evidence from research examining applications of
      Bandura's theory of self-efficacy in oncology suggests relationships between self
      efficacy and cancer prevention and self-efficacy and adaptation to cancer. Strong
      percepts of self-efficacy predict intention to quit smoking, increased
      participation in screening programs, and adjustment to cancer diagnosis.
      Increased self-efficacy is associated with increased adherence to treatment,
      increased self-care behaviors, and decreased physical and psychological symptoms.
      The advanced practice nurse is in an excellent position to give feedback that may
      help support patients' self-efficacy.

PMID- 9188269
TI  - Ethics and the geography of the nurse-patient relationship: spatial vulnerable
      and gendered space.
AB  - In a study that sought to understand the ethical concerns of home care and
      psychiatric nurses, relationship proved to be of central import. Yet the sense of
      relationship was not limited to, not even primarily, the interpersonal bond that
      is most commonly understood by relationship. For the nurses in this study,
      serious ethical concerns originated in those structural aspects of relationship
      reflecting the social space that patients and nurses occupy. These concerns can
      be broadly grouped into two categories, spatial vulnerabilities and gendered
      space. The ethical concerns of spatial vulnerability include poverty,
      exploitation of patients for institutional gain, homogenization of identity, and
      the fragmentation of care. Gendered space includes invisibility, instrumentality,
      and relations to other nurses. Geography may be a useful way to think about the
      nurse-patient relationship because relationship is itself a spatial term and
      because geography allows for the dimensionality of scale from the local or
      intimate to the global or structural. How we organize and structure our social
      relations is ethically significant.

PMID- 9188270
TI  - Caregiving: concept analysis and outcomes.
AB  - More than ever before, caregiving has become a salient public policy issue. A
      number of recent and anticipated demographic, economic and social changes have
      occurred that make it imperative for researchers to critically examine the impact
      of caregiving on family caregivers' health, behavior, emotions, and social
      status. Researchers at the University of Iowa College of Nursing are working to
      classify standardized nursing-sensitive patient outcomes for use in language
      development, practice, research, and education to evaluate the effectiveness of
      nursing interventions and clinical nursing services. This article focuses on
      family caregiving and the analysis of caregiver role performance in both direct
      and indirect care, linking outcomes and indicators, to enable nurses to promote
      the health of caregivers.

PMID- 9188271
TI  - Concept developmental analysis.

PMID- 9188272
TI  - Multiphoton-excited visible emission by serotonin solutions.
AB  - Nonlinear excitation of the neurotransmitter serotonin (5HT) in aqueous solution
      is shown to generate a blue-green-emitting photoproduct in addition to UV
      fluorescence characteristic of native 5HT. The visible emission rate in
      diffusional steady-state measurements scales as the sixth power of excitation
      intensity, demonstrating that absorption of six near-IR photons is required to
      generate emission of one visible photon. Transient measurements reveal that this
      process is composed of two sequential nonlinear steps, the first excited by four
      photons and the second by two photons. These results, in combination with
      measurements of multiphoton-excited serotonin UV fluorescence, support a model in
      which 5HT is photochemically transformed as a consequence of four-photon
      absorption (Etot approximately 6 eV) to a photoproduct that then emits in the
      visible region via two-photon excitation. A minimum bound of approximately 10(
      51) cm4 s photon-1 is observed for the two-photon emission action cross section
      at 830 nm. Photoionization, rather than reaction with a dissolved oxygen species,
      appears to be the primary mechanism for generation of the blue-green-emitting
      photoproduct. The peak intensities required to generate significant blue-green
      emission (approximately 5 x 10(11) W cm-2 from 80 MHz 150 fs titanium: sapphire
      laser pulses) are approximately five-fold higher than are typically used in two
      photon laser scanning microscopy but are still substantially lower than the
      estimated intensity needed to induce dielectric breakdown of water.

PMID- 9188273
TI  - Isolation and partial characterization of a novel psoralen-tyrosine
      photoconjugate from a photoreaction of psoralen with a natural protein.
AB  - The photoreaction of psoralens with DNA is a well-characterized reaction.
      However, the photoreactions of psoralens with proteins is not very well
      understood. Our objective was to isolate an amino acid-psoralen photochemical
      adduct. We photoreacted 8-methoxypsoralen (8-MOP) with T7 RNA polymerase, a
      protein that carries out the fundamental biological process of transcription.
      Amino acid composition analysis of the photoreacted polymerase revealed that
      tyrosines quantitatively reacted with 8-MOP. From the acid hydrolysates of the
      photoconjugated T7 RNA polymerase, an 8-MOP-tyr adduct was partially purified by
      HPLC. The purified 8-MOP-tyr adduct and related parent compounds were analyzed by
      UV-visible absorption, fluorescence and mass spectroscopy. Excitation/absorption
      spectra suggested that the pyrone of the original 8-MOP was modified in the
      isolated photoadduct, and that the adduct probably contained a benzofuran.
      Chemical ionization mass spectrometry was consistent with the photoaddition of
      tyr to 8-MOP with a conservation of the overall mass (+/-1 atomic mass units). As
      far as we know, this work represents the first instance of isolation and partial
      characterization of an amino acid-psoralen photoadduct.

PMID- 9188274
TI  - UV light-induced crosslinking of the complementary strands of plasmid pUC19 DNA
      restriction fragments.
AB  - Restriction fragments of pUC19 DNA were irradiated by various doses of UV light
      and analyzed by denaturing (alkaline) agarose gel electrophoresis. The
      irradiation generated retarded species whose mobility indicated two crosslinked
      DNA strands. Quantitative analysis of the experimental data provided an empirical
      equation relating the fraction of crosslinked DNA molecules to their length and
      to the dose of their irradiation by UV light. This equation can be used to
      predict the crosslinking behavior of pUC19-like DNA molecules whose primary
      structures do not much differ from a random nucleotide sequence. The amount of
      interstrand crosslinks increased with the (A+T) content of the pUC19 DNA
      fragments but the dependence was not clear-cut to indicate that oligonucleotide
      composition of DNA played a significant role as well.

PMID- 9188275
TI  - Photoreactivating enzyme for (6-4) photoproducts in cultured goldfish cells.
AB  - We previously reported that when cultured goldfish cells are illuminated with
      fluorescent light, photorepair ability for both cyclobutane pyrimidine dimers and
      (6-4) photoproducts increased. In the present study, it was found that the
      duration of the induced photorepair ability for cyclobutane pyrimidine dimers was
      longer than that for (6-4) photoproducts, suggesting the presence of different
      photolyases for repair of these two major forms of DNA damage. A gel shift assay
      was then performed to show the presence of protein(s) binding to (6-4)
      photoproducts and its dissociation from (6-4) photoproducts under fluorescent
      light illumination. In addition, at 8 h after fluorescent light illumination of
      the cell, the binding of protein(s) to (6-4) photoproducts increased. The
      restriction enzymes that have recognition sites containing TT or TC sequences
      failed to digest the UV-irradiated DNA photoreactivated by using Escherichia coli
      photolyase for cyclobutane pyrimidine dimers, indicating that restriction enzymes
      could not function because (6-4) photoproducts remained in recognition sites.
      But, when UV-irradiated DNA depleted of cyclobutane pyrimidine dimers was
      incubated with extract of cultured goldfish cells under fluorescent light
      illumination, it was digested with those restriction enzymes. These results
      suggested the presence of (6-4) photolyase in cultured goldfish cells as in
      Drosophila, Xenopus and Crotalus.

PMID- 9188276
TI  - Modification of global erythemally effective irradiance by clouds.
AB  - The role clouds play in the modification of global radiation is still a major
      uncertainty in the risk assessment of UV effects on ecological systems and human
      health. This study presents cloud transmission data obtained from measurements
      with Robertson-Berger meters and simultaneous cloud observations. The global
      transmission of erythemally weighted irradiance depends strongly on cloud amount
      and can be described by a cubic function. The comparison with results derived
      from long-term records of total global irradiance indicates no statistically
      significant difference between the attenuation of erythemal and total global
      radiation. The large variance of data results from lumping together data from
      different cloud types. Classification of data according to cloud forms yields a
      more satisfactory fit. The coefficient of the cubic term characterizes the
      ability of various cloud forms to attenuate UV radiation. It varies between 0.4
      for high clouds and approximately 1.0 for cumulonimbus. This attenuation
      parameter allows a quantitative description of the cloud influence on irradiance
      and therefore a more accurate risk assessment.

PMID- 9188277
TI  - Comparative action spectrum for ultraviolet light killing of mouse melanocytes
      from different genetic coat color backgrounds.
AB  - The photobiology of mouse melanocyte lines with different pigment genotypes was
      studied by measuring colony-forming ability after irradiation. The cell lines
      were wild-type black (melan-a) and the mutants brown (melan-b) and albino (melan
      c). Four lamps emitting various UV wavelengths were used. These were germicidal
      (UVC, 200-280 nm), 82.3% output at 254 nm, TL01 (UVB, 280-320 nm), 64.2% at 310
      311 nm, FS20, broadband with peak output at 312 nm and Alisun-S (UVA, 320-400
      nm), broadband with peak output at 350-354 nm. Appropriate filtration reduced the
      contaminating UVC to nonlethal levels for the longer waverange lamps. Wild-type
      melan-a was resistant to UVC and UVA compared to the other two cell lines, but
      the differences were small. The melan-c cell line was more resistant to UVB and
      markedly more resistant to FS20 than the pigmented lines. With the exception of
      FS20 responses, melan-b was more sensitive than melan-a to killing by the various
      UV lamps. There were more pyrimidine dimers (cyclobutane dimers and 6-4
      photoproducts) produced in melan-a than in melan-c cells by UVC, UVB and FS20
      lamps. Unlike melan-c, melan-a and melan-b showed a strong free radical signal of
      melanin character with a detectable contribution of pheomelanin-like centers. The
      contribution of pheomelanin was higher in melan-b than in melan-a, while the
      total melanin content in these two cell lines was comparable. The abundant
      melanin granules of wild-type melan-a melanocytes were well melanized and
      ellipsoidal, whereas those of melan-b melanocytes tended to be spherical. In the
      albino line (melan-c) the melanocytes contained only early-stage melanosomes, all
      of which were devoid of melanin. The results indicate that pigment does not
      protect against direct effect DNA damage in the form of pyrimidine dimers nor
      does it necessarily protect against cell death. High pigment content is not very
      protective against killing by UVC and UVA, and it may photosensitize in UVB the
      very wavelength range that is of greatest concern with respect to the rising
      incidence in skin cancer, especially melanoma. It is clear from these studies
      that, in pigment cells, monochromatic results cannot predict polychromatic
      responses and that cell death from solar irradiations is a complex phenomenon
      that depends on more than DNA damage.

PMID- 9188278
TI  - Quinolone antibiotic photodynamic production of 8-oxo-7, 8-dihydro-2'
      deoxyguanosine in cultured liver epithelial cells.
AB  - To study the basis for the phototoxicity of quinolones, a class of synthetic
      antibacterials, the photodynamic ability to mediate 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxo-dG) formation in cultured cells was measured for
      lomefloxacin (LMX), which is strongly associated with clinical phototoxicity in
      humans, and ciprofloxacin (CFX), which has few reports of phototoxicity. Adult
      rat liver (ARL-18) cells were exposed to the quinolones in the presence of UVA
      and DNA was extracted and analyzed by HPLC with electrochemical detection. Low
      levels of 8-oxo-dG were found in the DNA of nonirradiated ARL-18 cells and this
      was increased up to 6-fold in the presence of either LMX (50-400 microM) or up to
      3.6-fold in the presence of CFX (50-400 microM) and UVA (20 J/cm2) when compared
      to the UVA control. Comparing separate experiments with LMX and CFX, LMX produced
      greater levels of 8-oxo-dG either after dark exposure or after UVA exposure at 20
      J/cm2. Also, LMX and CFX were both shown to photodegrade in the presence of UVA,
      and it was determined that UVA photoinstability alone does not reflect phototoxic
      potential. These data suggest that the photodynamic potential of LMX and CFX to
      produce 8-oxo-dG may relate to their human clinical phototoxicity profile. We
      suggest that the observed clinical phototoxicity is mediated through a UVA
      photodynamic effect on the quinolone to form reactive oxygen species in the
      presence of molecular oxygen. The findings indicate that 8-oxo-dG formation can
      serve as a marker for the potential phototoxicity of new quinolones.

PMID- 9188279
TI  - In vivo laser-induced fluorescence imaging of a rat pancreatic cancer with
      pheophorbide-a.
AB  - Laser-induced fluorescence (LIF) of pheophorbide-a (Ph-a) was used for imaging of
      a rat pancreatic tumor. Using a dimensionless function (the ratio of Ph-a
      fluorescence by bluish autofluorescence), the fluorescence contrasts between
      excised tumors and their paired pancreas were investigated up to 48 h after a 9
      mg kg-1 Ph-a intravenous administration. Among five tested excitation
      wavelengths, 355 and 610 nm excitations gave the best distinctive contrasts, both
      48 h after dye injection. The LIF imaging of six intrapancreatic tumors and six
      healthy pancreas was carried out in vivo using two laser excitations: 355 nm
      (Nd:YAG + tripling) for bluish autofluorescence and 610 nm (rhodamine 6G dye) for
      reddish autofluorescence and dye emission. Images were recorded through bandpass
      filters at 470 and 640 nm (autofluorescence) and at 680 nm (dye +
      autofluorescence) with an intensified charged-coupled device camera.
      Autofluorescence as Ph-a fluorescence images did not allow accurate LIF diagnosis
      of pancreatic carcinoma. An image processing, including for each pixel a computed
      division of Ph-a fluorescence (after subtraction of reddish autofluorescence) by
      bluish autofluorescence intensity generated poorly contrasted tumor images in
      five of six and false tumor localization in one of three of the tumor-bearing
      pancreas. A fitting of the digital 640 nm autofluorescence up to the mean 680 nm
      fluorescence intensity in pancreas prior to subtraction allowed a safe diagnosis
      to be made with well-contrasted tumor images. To assess automation ability of the
      processing, a same fitting coefficient (mean of individual values) was applied.
      In this way, false-negative (one of six) and false-positive (two of six) images
      were present in tumor-bearing animals as false-positive in one-half of the
      controls. A successful standardized procedure was then applied with a
      normalization of 640 and 680 nm pancreas intensities to a same set threshold
      prior processing. In opposition to thin-layered hollow organs, such as bronchial
      tube or digestive tract, LIF imaging of carcinoma inserted in a compact organ is
      exhausting. The use of a dye excitable in the red wavelength range (610 nm for Ph
      a) may partly solve this problem, rendering LIF imaging more accurate and
      potentially automated.

PMID- 9188280
TI  - Sunscreen protection against ultraviolet radiation-induced pyrimidine dimers in
      mouse epidermal DNA.
AB  - Pyrimidine dimers were measured in epidermal DNA of SKH:HR1 mice following
      exposure to solar-simulated UV radiation (SSUV, 290-400 nm) or to UVA (320-400
      nm). Mice were exposed to SSUV or UVA after topical application (2 mg/cm2) of
      vehicle, a UVB absorber (5% 2-ethylhexyl p-methoxycinnamate [2-EHMC]), or a broad
      spectrum UVA absorber (5% Mexoryl SX). The rates of induction of pyrimidine
      dimers in untreated animals were 5.4 +/- 0.57 x 10(-4) (mean +/- SEM) and 7.6 +/-
      0.95 x 10(-6) dimers per 10(8) Da of epidermal DNA per J/m2 of SSUV and UVA,
      respectively. Topical application of Mexoryl SX reduced the rate of induction of
      pyrimidine dimers in SSUV-exposed animals to 4.7 +/- 0.44 x 10(-5) dimers per
      10(8) Da per J/m2 for a dimer induction protection factor (PF) of 11.5 (5.4 x 10(
      4)/4.7 x 10(-5). The rate of dimer induction in Mexoryl SX-treated, UVA-exposed
      mice was 0.95 +/- 0.2 x 10(-6) dimers per 10(8) Da per J/m2 (PF = 8.0). The 2
      EHMC at a concentration of 5% (wt/wt) was significantly less effective than
      Mexoryl SX in preventing the induction of pyrimidine dimers in animals exposed to
      either SSUV or UVA. The rates of dimer induction in 2-EHMC-treated mice were 8.2
      +/- 1.1 x 10(-5) and 3.8 +/- 0.33 x 10(-6) dimers per Da per J/m2 of SSUV (PF =
      6.6) and UVA (PF = 2.0), respectively. Upon normalizing to the efficacy for edema
      induction, UVA induced approximately one-fourth the number of pyrimidine dimers
      per equivalent edematous response when compared to SSUV.

PMID- 9188281
TI  - Light-dependent oxygen consumption in bacteriochlorophyll-serine-treated melanoma
      tumors: on-line determination using a tissue-inserted oxygen microsensor.
AB  - Successful application of anticancer therapy, and especially photodynamic therapy
      (PDT) mediated by type II (PDTII) processes, depends on the oxygen content within
      the tumor before, during and after treatment. The high consumption of oxygen
      during type II PDT imposes constraints on therapy strategies. Although rates of
      oxygen consumption and repletion during PDTII were suggested by theoretical
      studies, direct measurements have not been reported. Application of a novel
      oxygen sensor allowed continuous and direct in situ measurements (up to a depth
      of 8-9 mm from the tumor surface and for several hours) of temporal variations in
      the oxygen partial pressure (pO2) during PDT. Highly pigmented M2R mouse melanoma
      tumors implanted in CD1 nude mice were treated with bacteriochlorophyll-serine
      (Bchl-Ser; a new photodynamic reagent) and were subjected to fractionated
      illumination (700 < lambda < 900 nm) at a fluence rate of 12 mW cm-2. This
      illumination led to total oxygen depletion with an average consumption rate of
      7.2 microM(O2) s-1. Spontaneous reoxygenation (at an average rate of 2.5
      microM(O2)/s) was observed during the following dark period. These rates are in
      good agreement with theoretical considerations (Foster et al., Radiat. Res. 126,
      296, 1991 and Henning et al., Radiat. Res. 142, 221, 1995). The observed patterns
      of oxygen consumption and recovery during prolonged periods of light/dark cycles
      were interpreted in terms of vasculature damage and sensitizer clearance. The
      presented data support the previously suggested advantages of fractionated
      illumination for type II photodynamic processes.

PMID- 9188282
TI  - Safety analysis: relative risks of ultraviolet exposure from fluorescence
      spectroscopy and colposcopy are comparable.
AB  - Fluorescence spectroscopy is a promising tool for use in the diagnosis of disease
      in human tissue. However, few published reports have evaluated the safety of this
      technique, despite the fact that many spectroscopic systems use UV illumination.
      This study determined the relative risk associated with light exposure from
      spectroscopic systems compared with the traditional light sources that are used
      to illuminate tissue and direct biopsies. We compared spectroscopic detection
      systems for the cervix to the colposcope, a low-power microscope routinely used
      to illuminate the cervix, which does not cause any known photochemical damage. We
      measured the average spectral irradiance (W/[cm2nm]) and the average tissue
      exposure time during a diagnostic colposcopy examination. To quantify the
      relative risks, we multiplied illumination spectra by several action spectra from
      the literature and compared the areas under the curves corresponding to each
      procedure. The risk associated with the average power colposcope served as our
      basis for comparison. We conclude that the risks of illumination using
      spectroscopic systems are lower than or comparable to those already encountered
      in routine diagnostic procedures such as colposcopy with an average power
      colposcope. Spectroscopic examination can be associated with a somewhat higher
      risk than a colposcopy with the lowest power colposcope or a shorter than average
      colposcopy. The analysis presented can be repeated to estimate the magnitude of
      risks associated with other spectroscopic diagnostic devices.

PMID- 9188283
TI  - Effect of dosimetric and physiological factors on the lethal photosensitization
      of Porphyromonas gingivalis in vitro.
AB  - The aims of this study were to (1) determine the effect of dosimetric and
      physiological factors on the lethal photosensitization of Porphyromonas
      gingivalis using toluidine blue O (TBO) and light from a helium/neon (HeNe)
      laser; (2) determine the influence of sensitizer concentration, preirradiation
      time, serum and growth phase on sensitizer uptake by P. gingivalis. The
      dosimetric factors studied were concentration of TBO, light dose and
      preirradiation time. The physiological factors were presence of serum, pH and
      bacterial growth phase. Sensitizer uptake by P. gingivalis under various
      conditions was determined using tritiated TBO (3H-TBO). In the presence of TBO, a
      light dose-dependent increase in kill was attained (100% kill at 4.4 J). There
      was no significant effect on the numbers killed when TBO was increased from 12.5
      to 50 micrograms/mL. An increase in preirradiation time gave slightly increased
      kills. High kills were achieved at all three pH (6.8-8.0). Although kills were
      substantial in the presence of serum, they were significantly less than those
      obtained in the presence of saline. Cells in all three growth phases were
      susceptible to lethal photosensitization, although stationary phase cells were
      slightly less susceptible. Maximum uptake of TBO occurred within 60 s and uptake
      in serum was less than in saline. The uptake by the log phase cells was greater
      at lower concentrations of sensitizer (50 micrograms/mL), compared to the other
      two phases.

PMID- 9188284
TI  - Charge movements in the 13-cis photocycles of the bacteriorhodopsin mutants R82K
      and R82Q.
AB  - We have examined light-induced currents in oriented membranes of the
      bacteriorhodopsin mutants R82K and R82Q. Our results suggest that two
      photocurrent components found in R82K, with 30 and 300 microseconds lifetimes,
      are due to the photocycle of the 13-cis rather than the all-trans form of the
      pigment. We investigated the pH dependence of these components and their
      correspondence to absorbance changes at 660 nm characteristic of
      photointermediates of the 13-cis cycle. The presence of a D2O effect suggests
      that the charge motions producing these photocurrents are related to proton or
      protonated amino acid movement within the molecule. The current amplitudes depend
      on the protonation states of at least two residues, D85 and (probably) E204. In
      R82Q, a 10 microseconds photocurrent is observed that also depends on the
      protonation state of D85 and is similar to the 30 microseconds current in R82K.
      We attempt to explain these currents in terms of a model for interacting residues
      in the extracellular half of the bacteriorhodopsin channel.

PMID- 9188285
TI  - Evidence-based practice.

PMID- 9188286
TI  - The natural evolution of postpartum fatigue among a group of primiparous women.
AB  - A prospective, longitudinal study was conducted to examine the natural evolution
      of levels of fatigue, as measured by the Visual Analogue Scale-F, among a group
      of 36 primiparous women during the first 6 weeks postpartum. The results revealed
      that this group of women experienced higher levels of morning fatigue across the
      6 weeks than had previously been reported. Their morning fatigue peaked at 4
      weeks and then slowly decreased. At the 6th week, the group mean for morning
      fatigue was 1.42 points (on a 100-point scale) lower than at the 1st week
      postpartum, suggesting women do not completely recover from the effects of
      pregnancy, childbirth, and transition to parenthood by 6 weeks postpartum.
      Maternal age and length of labor were found to be significantly related to the
      levels of fatigue and energy at various times during the 6 week postpartum
      period.

PMID- 9188287
TI  - Gastric decompression in adult patients. Survey of nursing practice.
AB  - Using a 62-item investigator-developed mailed questionnaire, this descriptive
      study of 350 randomly selected staff nurses sought to identify variations in
      practices in the care of patients with nasogastric tubes. Reported here are the
      results on the 15 questionnaire items related to the use of nasogastric tubes for
      gastric decompression. Results show that practice is not always consistent with
      published research; additionally, there are areas of practice for which no
      research was found. Subjects' responses by age, education, and amount of
      experience showed marked frequency variations on several items, as did employment
      in teaching versus community hospitals. Results have implications for nursing
      educators in clinical agencies and nursing schools.

PMID- 9188288
TI  - Irritable bowel syndrome. An exploration of the patient perspective.
AB  - Although research into the etiology of irritable bowel syndrome (IBS) is
      extensive, this is not true for the patient experience of IBS. International
      population studies indicate that 15-20% of persons suffer from IBS. IBS is one of
      the eight most common somatic symptom complexes that account for 23% of visits to
      primary care physicians. This article details the journey of IBS sufferers in
      their attempt to understand and manage their illness through documenting patient
      perceptions of the origin of the illness, their search for treatment, their
      present management strategies, and their need for information and control. A
      grounded theory approach is used. Clinical practice protocols reflect the state
      of knowledge surrounding IBS: The variables are many and diagnosis and outcomes
      are uncertain. Further, our data suggest there is a desperate need for support
      groups and opportunities for patients, physicians, and supportive others to share
      experiences and concerns.

PMID- 9188289
TI  - Adaptation to suffering. Meaning and implications for nursing.
AB  - Nurses daily encounter persons who are suffering, but few have studied the
      suffering experience. Although the phenomena has been observed in the clinical
      setting, scientific inquiry has been limited. The meaning of suffering was
      explored through semistructured interviews with 20 subjects who had multiple
      sclerosis. The adaptation to suffering model provided the conceptual framework
      for this qualitative study. Stressors (e.g., problems associated with multiple
      sclerosis) and strategies perceived as helpful were identified. Subjects'
      responses about their suffering experiences followed an hierarchical progression
      from shock and denial through acceptance and understanding to finding meaning in
      their suffering. Rank ordering of responses illustrated the components of
      adaptation and how they changed with duration of illness. Findings provided
      support for the theoretical model and the importance of assisting clients to find
      meaning in their suffering experiences.

PMID- 9188291
TI  - Decreasing intracoronary stent complications.
AB  - With the release of intracoronary artery stents, the role of the critical care
      nurse is vital in decreasing complications in the stented patient as well as
      optimizing patient outcomes. The importance of understanding and adhering to
      anticoagulation and activity protocols is a must for successful patient
      management.

PMID- 9188290
TI  - The effect of xanthines on fluid balance.
AB  - To determine whether drinks containing caffeine and theophylline cause more fluid
      loss than equivalent amounts of non-xanthine drinks, a convenience sample of 30
      adults between the ages of 57 and 81 was selected. Subjects were picked for 2
      groups: those who had developed tolerance to these xanthines and used them freely
      (the X Group) and those who habitually omitted drinks containing xanthines from
      their diets (the NO X Group). Both groups consumed approximately 2 liters of
      fluid daily for 5 days. When overall means were compared by analysis of variance,
      the two groups did not differ on serum osmolality for Day 5, change in serum
      osmolality (from Day 0 to Day 5), adjusted I/O ratio, percent weight change from
      Day 0, or percent weight change from previous day. Analysis of the same variables
      on a daily basis indicated that the X group was better hydrated on Day 4.

PMID- 9188292
TI  - Managing patients with acute myocardial ischemia and reperfusion injury with N
      acetylcysteine.
AB  - Previously administered in cases of acetaminophen toxicity, N-Acetylcysteine
      (NAC) is now also being used in the management of acute myocardial ischemia and
      reperfusion injury. NAC potentiates the beneficial effects of nitrates such as
      nitroglycerin and reduces oxidative stress on the heart. The critical care nurse
      plays an important role in optimizing the therapeutic benefits of NAC and
      minimizing its potential harmful effects.

PMID- 9188293
TI  - Patients' recollections of critical care.
AB  - Warm, caring, competent critical care nurses who communicate respect for
      patients' dignity and individuality alleviate fear and stress of a critical care
      unit stay. Patients perceive these nurses as professionals who deliver quality
      care. When cared for by critical care nurses with these characteristics,
      patients' satisfaction with care is heightened. This article provides an insight
      to patients' responses concerning their care in a critical care unit.

PMID- 9188294
TI  - Restraining an aggressive suicidal, paraplegic patient: a look at the ethical and
      legal issues.
AB  - This paper focuses on a case of an intently suicidal, paraplegic patient in a
      critical care unit and the need for collaboration among nursing leaders to
      provide a safe environment through the use of wrist restraints. Ethical questions
      regarding patient rights, liberties, and privileges are reviewed. Legal points of
      negligence and intentional torts are also included in the analysis of the case.

PMID- 9188295
TI  - A model for teaching critical thinking in the clinical setting.
AB  - As the scope of nursing practice changes, the ability of nurses to think
      critically and make appropriate clinical judgements becomes even more necessary.
      The author shares a model for teaching critical thinking and describes how it can
      be used to improve the critical thinking skills of critical care nurses.

PMID- 9188296
TI  - Thoughts on competing in the evolving health care system.

PMID- 9188297
TI  - AIDS residential care.

PMID- 9188298
TI  - A nurse owned and managed home health agency.
AB  - The downsizing epidemic that has swept across the country's acute care facilities
      has forced many nurses to reassess their goals and explore different career
      options. Home care has become an important alternative to hospital nursing for
      many nurses. During a management reorganization of a major medical center in
      Oakland, California, in early 1993, several middle managers in the nursing
      department were laid off. What started as informal, support group meetings to
      help one another face the transition and explore new career alternatives led to
      the formation of Professional Health Care at Home (PHCH). PHCH is a nurse owned
      and operated home care agency serving homebound patients in the San Francisco Bay
      Area. In these initial meetings, many nurses expressed an interest in home care
      and discovered the talent in their group that enabled them to start their own
      company.

PMID- 9188299
TI  - Home health aides: home care's endangered species. 1.

PMID- 9188301
TI  - Critical care nursing in the home: an expanding opportunity for nurses, patients,
      and families. Interview by Sarah F. Zarbock.

PMID- 9188300
TI  - Grant writing rewards the community and the home care team.
AB  - We have found it well worth the time and effort expended to write grants. Results
      have benefited the community in lives saved, long-term disability prevented,
      human suffering reduced, parents empowered, and more than 30,000 St. Louis
      families served. The only way to learn grant writing is to just do it! Writing
      grants is a vehicle to community service. The potential rewards are immeasurable
      for both the community and yourself.

PMID- 9188302
TI  - New agents available for the treatment of diabetes.

PMID- 9188303
TI  - Guidelines for control of tuberculosis.

PMID- 9188305
TI  - Shifting moralities: from sanctity of life to quality of life.

PMID- 9188304
TI  - Home care past, present, and future: opportunities and challenges in a managed
      care environment.
AB  - This article describes the history of Medicare-based home care and the changing
      requirements of the home care industry as the reimbursement models continue to
      evolve. Medicare-based home care was once seen as an ancillary service of the
      hospitals. Now, with the advent of managed care, home care provides new options
      and opportunities and is facing new challenges at both the local and the national
      levels. Current proposals in Washington, such as bundling, co-pays, and a
      Prospective Payment System, will have farreaching effects on the industry. This
      article discusses the various reimbursement models, including Medicaid, Medicare
      HMOs, managed care, and capitation, and identifies key areas and opportunities
      for home care in the future.

PMID- 9188306
TI  - Creating value through integrating postacute care.

PMID- 9188307
TI  - Tips for effective teaching.
AB  - For all of us, one side of the brain, right or left, is the dominant hemisphere
      used to process information. In 9 out of 10 persons, the left temporal lobe
      becomes the dominant hemisphere. In the remaining one tenth of the population
      both sides develop at the same rate, forming "dual dominance," or, more rarely,
      the right side alone becomes highly developed. The left hemisphere of the brain
      serves as the analytical, sequential, cause and effect processor, whereas the
      right hemisphere of the brain is the mind's eye, assimilating information
      simultaneously and processing visual and nonverbal information and sound. Neither
      hemisphere works independently, and both are used to effectively learn new
      information. The creative teacher understands this arrangement and can
      successfully determine when a complex diagram or video is needed to teach a
      patient, or when only a clear voice is necessary.

PMID- 9188308
TI  - "Don't fence me in": my philosophy of nursing.

PMID- 9188309
TI  - Merger mania: a view from a physician.

PMID- 9188310
TI  - On accreditation of healthcare organizations. An overview of 1997-1998.
      Accreditation Standards for Home Care.

PMID- 9188311
TI  - Creating value through integrating postacute care, Part 2.

PMID- 9188312
TI  - Initiatives aim to integrate performance measures into the Joint Commission's
      Accreditation process.

PMID- 9188313
TI  - Home health aides: home care's "endangered species".

PMID- 9188314
TI  - The role of occupational therapy in home care.
AB  - Occupational therapy is a health discipline and rehabilitation profession based
      on the premise that "occupations," such as ordinary everyday activities (work,
      play, self-care), have a restorative or normalizing effect. The goal of
      occupational therapy is to assist patients in achieving a maximum level of
      independent living by developing the capacities that remain after disease,
      accident, or deformity.

PMID- 9188315
TI  - Assessing homeless veterans using the Omaha Assessment Tool in a nontraditional
      home care setting.
AB  - Homelessness is having an inappropriate place to stay and sleep and not having a
      mailing address for a period of overnight to 6 months or more. The homeless
      population is diverse and difficult to count.

PMID- 9188316
TI  - Preparing to identify and intervene in health care.
AB  - The national prevalence of elder abuse is unknown, and estimates vary from study
      to study. Currently, 1.2 to 2 million older Americans are believed to be victims
      of elder abuse each year. Researchers and clinicians concur that elder abuse is
      underreported, is a serious problem, rarely occurs as an isolated event, persists
      over extended periods, and requires coordinated intervention.

PMID- 9188317
TI  - Rethinking compensation.
AB  - A great deal has been written about the increase in managed care and its impact,
      both real and potential, on home health care. Those articles generally have
      focused on the limitations of managed care related to patient care and patient
      outcomes--are they better or worse than in traditional Medicare home care?

PMID- 9188318
TI  - Can alendronate help my osteoporosis?
AB  - Bone is an active tissue, undergoing continuous remodeling to renew and replace
      the skeleton. Remodeling involves resorption (breakdown) followed by formation.

PMID- 9188319
TI  - Gazing into the Medicare crystal ball.
AB  - In this strange, uncharted, and often dangerous territory we call "managed care,"
      having a crystal ball would be helpful. We could gaze into it to find out what's
      in store for all of us, whether we are health care providers, consumers, or both.

PMID- 9188321
TI  - Developing a strategic plan for the nursing workforce: the California experience.

PMID- 9188320
TI  - The epidemiology of disease transmission.
AB  - As inhabitants of the planet Earth, we live in a veritable sea of microorganisms.
      Virtually every aspect of our environment is heavily populated with different
      forms of microbial life. From the air we breathe to the food we eat, our daily
      existence is in the direct presence of literally billions of microorganisms.

PMID- 9188322
TI  - Partnerships between home care providers and client families.
AB  - As home care providers, we work with clients who are members of family units. The
      influence of family on the client is ever present, whether it takes the form of
      participation, resistance, denial, judgment, withdrawal, or absence. Even if the
      home care provider never meets them, relatives will influence the client's
      behavior.

PMID- 9188323
TI  - Resuscitating your cardiopulmonary skills.
AB  - The emotions that prompt patients who have suffered a heart attack and their
      families to seek cardiopulmonary resuscitation (CPR) training are sometimes the
      very things that inhibit learning. Shock, denial, anger, and fear can have an
      adverse impact on the opportunity to master vital skills.

PMID- 9188324
TI  - Quality of care for dialysis patients: national initiative focuses on improved
      treatment.
AB  - The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) is
      a groundbreaking project established to develop evidence-based dialysis treatment
      guidelines. Highlights of the guidelines were presented to the renal community in
      November 1996 at the National Kidney Foundation's Annual Scientific Meeting in
      New Orleans.

PMID- 9188326
TI  - HIV/AIDS in the elderly: a hidden population.

PMID- 9188327
TI  - Osteoporosis: primary prevention and intervention strategies for women at risk.
AB  - The growth and development of the skeleton begins in early fetal life and
      continues for nearly two decades in a series of well-defined events. Minerals-
      particularly calcium but also carbonate, magnesium, sodium, and fluoride--play
      vital structural and metabolic roles in bone growth and development. However,
      bone formation also is encouraged by hormones, such as estrogen, and by weight
      bearing activity. Living bone is never metabolically at rest; its matrix and
      mineral stores are being remodeled constantly along the lines of mechanical
      stress.

PMID- 9188325
TI  - Assisting lay family caregivers: promoting independence as a method of coping.

PMID- 9188328
TI  - When is a nurse practicing medicine?

PMID- 9188329
TI  - American Subacute Care Association. The R.A.C.E. to integration: translating
      strategy into action.

PMID- 9188330
TI  - Preparing for your Joint Commission survey.

PMID- 9188331
TI  - Clostridium difficile: a microbial enigma.
AB  - Nearly 150 years ago, Louis Pasteur introduced the world to the science of
      microbiology and to the fact that our environment contains microbes capable of
      causing disease. Subsequent to these discoveries, a pandemic of health care
      related staphylococcal infections nearly a century later led to the recognition
      of hospital-associated (nosocomial) infection. Clearly such infections
      (nosohusial) now also afflict nursing home residents and patients who receive
      home health care.

PMID- 9188332
TI  - Trust and physician-assisted suicide.
AB  - In the first week of January, the U.S. Supreme Court began hearing arguments in
      the matter of assisted suicide. The prohibition against physician-assisted
      suicide (PAS) in Oregon, New York, and Washington is being challenged.

PMID- 9188333
TI  - Some observations on policy for research and development in the NHS.

PMID- 9188334
TI  - Clinical supervision.
AB  - The introduction of clinical supervision to a wider sphere of nursing is being
      considered from a professional and organizational point of view. Positive views
      are being expressed about adopting this concept, although there are indications
      to suggest that there are also strong reservations. This paper examines the
      potential for its success amidst the scepticism that exists. One important
      question raised is whether clinical supervision will replace or run alongside
      other support systems.

PMID- 9188335
TI  - A conceptual framework for advanced practice: an action research project
      operationalizing an advanced practitioner/consultant nurse role.
AB  - A preliminary conceptual framework for an advanced practice/consultant nurse role
      is presented which links the role to its context and outcomes. The conceptual
      framework was developed in the process of analysing data from a 3-year action
      research study involving the operationalization of an advanced
      practice/consultant nurse role in a Nursing Development Unit. The skills and
      knowledge base of consultancy, underpinned by a strong nursing foundation,
      augmented by strong leadership and combined with the educator and researcher
      functions, are presented as the attributes of the advanced
      practitioner/consultant nurse. The facilitation of a transformational culture is
      highlighted as central to the skills and processes used within the role.
      Implications for the preparation and accreditation of the advanced
      practitioner/consultant nurse are highlighted.

PMID- 9188336
TI  - Anticipating and experiencing post-operative pain: the patients' perspective.
AB  - This study uses a qualitative approach to explore patients' expectations and
      experiences of pain, factors contributing to the effective/ineffective management
      of their pain and strategies patients reported as helpful when experiencing pain.
      Ten patients on a mixed surgical ward at a District General Hospital in the south
      of England participated in the study. Pain scores, using a visual analogue scale,
      were obtained for 'expected' pain preoperatively and 'worst pain experienced'. A
      taped in-depth interview exploring patients' experience of pain after surgery
      took place on the fifth post-operative day. Details of analgesia were also
      collected for the 5 days following surgery. Patients expected pain after surgery
      but the intensity of the pain they experienced was often significantly greater
      than anticipated. Lack of information, inadequate pain assessment and ineffective
      pain control contributed to this finding. It is suggested that new pain
      technology, such as epidural and patient-controlled analgesia, may not change the
      prevalence and incidence of pain unless the systems these technologies are placed
      within also change.

PMID- 9188337
TI  - When touch is not the best approach.
AB  - Health care professionals have long believed in the value of nonverbal components
      of communication and the highly significant roles such factors as distance,
      space, and touch can play in therapeutic relationships. The value of touch is not
      appreciated by all health care professionals or considered appropriate or
      desirable by some patients. While touch has been described as the most important
      of all the senses, the astute professional must be cognizant of the times when
      touch should not be used.

PMID- 9188339
TI  - Underwater seal chest drains: the patient's experience.
AB  - Chest drains are routinely inserted during thoracic surgery and to conservatively
      manage spontaneous pneumothorax. An extensive search of the literature revealed
      only a small number of highly prescriptive articles to advise the nurse on the
      specific care needs of this patient group. An exploratory study undertaken with
      18 patients drew attention to the persistent discomfort and pain experienced by
      patients throughout the entire time that the chest drain remained in situ. Most
      of the patients also experienced short-lasting but intense pain when the chest
      drain was removed. Patients appeared ill-prepared for their experiences despite
      opportunities to obtain verbal and written information from staff.

PMID- 9188338
TI  - The nursing record as a research tool to identify nursing interventions.
AB  - This paper describes a study which was designed to test the feasibility of using
      retrospective case note abstraction of data from nursing records to identify the
      nursing interventions given to two groups of patients: those who had suffered a
      myocardial infarction and those who had sustained a fractured neck of femur. The
      aim of the study was to assess whether the data obtained from the records were an
      accurate reflection of the nursing care given to patients. This was done by
      comparing what was recorded in the notes for specific areas of care with what the
      nursing staff said they did. The specific areas of care for patients suffering a
      myocardial infarction were: pain, mobility, anxiety, patient education. The
      specific areas of care for patients sustaining a fractured femur were: pressure
      areas, pain, nutrition, mobility and rehabilitation, information and teaching.
      Data were collected in three ways: using a retrospective data abstraction tool to
      examine the case notes of a particular patient; interviewing a nurse who had
      looked after the same patient; interviewing a senior ward nurse to obtain
      information about ward policies and practices to obtain a profile of the care
      usually given to these groups of patients. In this paper we present some of our
      findings and discuss the methodological and logistical problems of using this
      method.

PMID- 9188340
TI  - Where do I stand? Legal implications of telephone triage.
AB  - The introduction of telephone triage in many accident and emergency (A&E)
      departments is seen as a way to give clients information immediately on demand,
      to assess and prioritize the need for treatment and to direct the client to the
      most appropriate service available. This article aims to examine the medico-legal
      aspects of telephone triage and the nurse's responsibility to the caller and
      themselves. It will involve looking at triage as a nursing function and how the
      nurse may minimize the threat of liability by beginning to understand the legal
      implications of giving advice by telephone. The article will also discuss the use
      of detailed documentation and communication skills and will aim to show how
      important these are in the protection of nurses in a court of law.

PMID- 9188341
TI  - The emotional work of caring, with a focus on gynaecological nursing.
AB  - In this paper the author briefly reviews the concept of caring. Emphasis is given
      to the emotional component and its management in caring relationships. This is
      illustrated with reference to a study of gynaecological nursing. Analysis of
      nurses' perceptions and experiences revealed situations particularly relevant to
      empathy and emotional work in caring for gynaecological patients.

PMID- 9188342
TI  - The experiences of mothers caring for a child with severe atopic eczema.
AB  - Atopic eczema is a relatively common disease which frequently occurs during
      childhood. This paper reports the findings of a research study which explored the
      effects upon family life of caring for a child with severe atopic eczema. Seventy
      seven accounts written by mothers of preschool children with this disease were
      analysed using qualitative latent content analysis. The focus of this paper is on
      the implications of the disease for the mothers' role and the additional work
      generated by the disease. The implications of these findings for nursing
      practice, in particular the work of health visitors and paediatric community
      nurses, is discussed. Throughout this paper the term 'nurse' is used to describe
      both nurses and health visitors.

PMID- 9188343
TI  - What training do preceptors require?

PMID- 9188344
TI  - Declaration of good character. What does this mean?

PMID- 9188345
TI  - Chest pain assessment tools.

PMID- 9188346
TI  - Beyond expertise: theory, practice and the reflexive practitioner.
AB  - This paper reconsiders Benner's book From Novice to Expert, in which the expert
      is portrayed as a reflective practitioner who works intuitively, drawing almost
      unconsciously on a repertoire of context-specific paradigm cases. In the light of
      more recent writings on informal, practice-based theory, it is suggested that
      there is a sixth level beyond expertise which is characterized by mindful
      practice and informal theory building. At this level, the practitioner constructs
      informal theory out of practice, applies that theory back into practice, and
      reflexively modifies the theory as a result of the changed clinical situation.
      Seen in this way, theory and practice are two parts of the same process, and the
      theory-practice gap is closed.

PMID- 9188347
TI  - 'To be or not to be'--an ethical debate on the not-for-resuscitation (NFR) status
      of a stroke patient.
AB  - Nursing has been described as a moral endeavour (Seedhouse, 1988; Berger et al.,
      1991), the art of dealing with ethical issues of right and wrong. Within the
      nursing literature, ethical issues are a major topic for discussion. Berger et
      al. (1991) explain that this reflects larger societal concerns about ethics in
      business, industry and government. The development of advanced technology and
      life-sustaining treatments such as cardiopulmonary resuscitation (CPR) has
      heightened the dilemmas of moral decision making. CPR was developed in the 1960s
      as an emergency life-saving procedure, although it is currently used on anyone
      who does not have a not-for-resuscitation status (Anon., 1980). In this paper, an
      ethical issue involving the decision of whether or not to resuscitate a stroke
      patient is discussed. An overview of the main ethical theories is presented
      because they provide a framework for an explication of ethical decision-making.
      The options available to those involved are then discussed in relation to
      relevant research. Finally, a conclusion is drawn from the ensuing situation.

PMID- 9188348
TI  - The quality and management of written information presented to women undergoing
      hysterectomy.
AB  - A study of a random sample of hospitals in England that provide information
      leaflets for women undergoing hysterectomy indicates a large variation in
      quality. In general, the findings reveal that written information for patients is
      given a relatively low priority. Production and dissemination of information for
      hysterectomy patients is somewhat ad hoc. It is not clear that any evaluation of
      the leaflets has been conducted to prove the efficacy of the available
      literature. While the majority of leaflets include information deemed essential
      by past hysterectomy patients, the presentation of the recovery process often
      implies no control for the patient, and conceives normality with a narrow
      perspective about what healthy behaviour means for women. The provision of a
      specific timetable for resumption of housework duties in 65% of the leaflets is a
      case in point. On the basis of the results of the survey, recommendations are
      made concerning the improvement of the standard of patient information leaflets.

PMID- 9188349
TI  - Towards a defence of nursing routine and ritual.
AB  - Healing routines and rituals have been an essential part of life since time in
      memorial. Rather than dismiss modern healing rituals because, in many instances,
      they appear to have no empirically proven manifest function, an argument is
      proposed in defence of routine and ritual, suggesting that there is an urgent
      need to explore their meaning or latent function.

PMID- 9188350
TI  - Chronic illness: the importance of support for families caring for a child with
      cystic fibrosis.
AB  - The effect of chronic life-threatening illness on the family is one of the major
      problems confronting the health-care system today. Increasingly, parents have the
      major responsibility for the daily management of their child's condition. There
      is evidence that many parents lack the professional help and support which could
      ameliorate some of their problems. It is important that nurses have an
      understanding of how families cope with the burden of caring for a chronically
      ill child. Health professionals need clear guidelines on how to support these
      families in their role as primary care-givers. This paper examines how families
      of children with cystic fibrosis adapt to the illness in order to provide
      indicators for nursing practice and to enhance the care and support provided for
      these families. Effective coping strategies include: assigning meaning to the
      illness, sharing the burden, denial of diagnosis and incorporating therapy in a
      schedule.

PMID- 9188351
TI  - Critical incidents, crucial issues: insights into the working lives of registered
      nurses.
AB  - The critical incident technique has been used in nursing in a number of ways: in
      developing understanding of the nursing role, as a quality assurance strategy, as
      an assessment and evaluation tool, and as an aid in the fostering of reflective
      practice. This article describes how the technique, used as a theoretical course
      assessment for a group of students studying long ENB courses, could be used to
      shed light upon issues regarded as crucial in the daily working lives of this
      group of registered nurses, and upon the reflective skills which they were able
      to employ.

PMID- 9188352
TI  - Evaluation of stress prevention and management workshops in the community.
AB  - Little emphasis has been placed by clinicians on the need for routine evaluation
      of outcomes of community mental health nursing interventions. Although numerous
      descriptive studies exist, there is little systematic evaluation of the work of
      community mental health nurses, and this problem is particularly acute in the
      field of preventative work. This paper presents the results of a small initiative
      to incorporate outcome evaluation into the clinical work of a community mental
      health team. Ninety-nine participants in a series of stress management workshops
      completed stress questionnaires before a series of 2-day workshops and were
      followed up at between 3 and 6 months afterwards. At follow-up, participants
      reported greater gains in terms of stress management than did no-treatment
      controls. The study offers tentative evidence for the effectiveness of community
      mental health nurses in offering effective preventative interventions and also
      indicates that such interventions are amenable to outcome evaluation within the
      context of routine clinical practice.

PMID- 9188353
TI  - Nurses achieve quality with pre-assessment clinics.
AB  - Nurses in a group of Wolverhampton Hospitals carried out a local research study
      to identify not only the level of patient satisfaction with pre-assessment
      clinics (PAC), but also what care nurses delivered in these clinics. Data were
      collected using both ethnographic and survey methods. Patients found the PAC
      visit valuable: it reduced stress and provided much needed information about the
      coming surgery. The skills nurses used and the tasks carried out were consistent
      throughout the Trust, and reflected the provision of a high standard of care.

PMID- 9188354
TI  - Changes in reported dietary habit and exercise levels after an uncomplicated
      first myocardial infarction in middle-aged men.
AB  - Education of patients and their partners about appropriate lifestyle changes
      following myocardial infarction (MI) is a key element in rehabilitation;
      developing relevant educational strategies requires a knowledge of patient
      beliefs and attitudes. This paper reports findings from a survey of diet and
      exercise in a group of 153 middle-aged men who had suffered a first uncomplicated
      MI. Just over half of those questioned expressed a desire to change their diet
      post-MI; those who perceived their pre-morbid diet to be 'less healthy' were more
      likely to want to change. Significant changes in food consumption (towards a more
      healthy diet) were observed at 3 months post-MI. Patients were less likely to
      change their behaviour with respect to exercise, and few attained recommended
      levels of physical activity either pre- or post-MI. Patients held a number of
      misconceptions regarding the role of diet and exercise in predisposing to
      coronary heart disease, and the need for change in behaviour. Beliefs and
      behaviour change were only weakly associated with receipt of information and
      advice. The findings have important messages for the more appropriate targeting
      of information-provision during the period of rehabilitation.

PMID- 9188355
TI  - Nurses caring for families--issues in a multiracial society.
AB  - Social, racial and ethnic factors are examined as key issues which affect nurses
      caring for families. A co-ordinated approach to caring for all families means
      that diverse clinical or therapeutic nursing may result. Quality caring for all
      families requires improved education, at pre- and post-registration levels, about
      the relationship between race and ethnicity and families' health, and the
      treatment regimens undertaken by families. Effective caring for families from
      different social, racial and ethnic groups is still at a rudimentary level.
      Orem's (1989) self-care nursing model is explored to show how ethnic differences
      and similarities among families are incorporated into caring.

PMID- 9188356
TI  - The effect of the husband's presence during labour in Hong Kong.

PMID- 9188357
TI  - When biology fails... will economics prevail?

PMID- 9188358
TI  - Relationship between pretransplant noncompliance and posttransplant outcomes in
      renal transplant recipients.
AB  - Approximately 5% to 18% of kidney transplant recipients do not comply with their
      posttransplant medical treatment. This study examined the relationship between
      pretransplant noncompliance and posttransplant outcomes. Using a longitudinal
      retrospective chart audit, pretransplant and posttransplant data were collected
      for 126 kidney transplant recipients over a 3-year period. Sixty-one percent of
      those identified as noncompliant before transplant lost their graft or died after
      transplant. Significant relationships between pretransplant noncompliance and
      graft loss and between pre- and posttransplant noncompliance were found.
      Clinicians must identify those with pretransplant noncompliance, as they are at
      risk for poor outcomes and might benefit from an intensive posttransplant follow
      up regimen.

PMID- 9188359
TI  - An evaluation of the effectiveness of a videotape for discharge teaching of organ
      transplant recipients.
AB  - Patients' understanding of discharge teaching is an essential factor for
      compliance with medications and follow-up care after an organ transplant. This
      study compared the knowledge gained by the current method of individualized
      discharge teaching with that same teaching method plus a videotape. Fifty
      participants were assigned alternately to two groups. A written test was used to
      assess knowledge after teaching. Test scores indicated that the two methods were
      equally effective. Qualitative data gathered during interviews indicated that
      both groups were equally satisfied with their education. It was concluded that
      videotaped education is an acceptable and effective strategy when used in
      conjunction with other methods. Varying the medium for education will meet the
      unique learning needs of more patients.

PMID- 9188360
TI  - Quality of life outcomes associated with variable posttransplant prednisone
      dosing regimens.
AB  - Prednisone tapering has become more common in the management of transplant
      recipients. Benefits of this practice, however, must be weighed against the
      risks. This study identified outcomes associated with variable low dose
      prednisone protocols. The study sample included 98 kidney and kidney-pancreas
      transplant recipients 1 year after transplant. Graft function, side effects of
      steroid therapy, and quality of life were recorded on patients receiving 0 (n =
      5), 1 to 5 (n = 4), 5 to 7.5 (n = 5), 7.5 to 10 (n = 21), and greater than 10
      mg/d prednisone (n = 63). Despite the fact that patients were assigned to the low
      dose groups because they were at risk for or already experiencing steroid induced
      side effects, the low dose groups presented side effect and quality of life
      profiles similar to or better than those of the standard dose group.

PMID- 9188361
TI  - Perceptions and attitudes toward organ procurement and transplantation: a medical
      community survey analysis.
AB  - The practitioner who recognizes and facilitates donor referral plays a pivotal
      role in the donor process. Mechanisms that help to identify and resolve issues
      for these practitioners are crucial. To identify barriers and issues that the
      community perceives as important, a survey to elicit the perceptions, attitudes,
      and ethical values of its respondents-specifically with regard to the donor
      process-was commissioned. The main components of the instrument included
      perceived problems, attitudes and ethical values, knowledge of consent process,
      medical and legal knowledge of brain death, organ procurement organization
      problems and suggestions for improvement, future education recommendations, and
      socio-demographic characteristics of the respondent. The survey confirmed issues
      of concern and brought to surface issues that have an underlying negative
      influence on the donor process.

PMID- 9188362
TI  - Thirty hours from referral to cross-clamp: a case study in organ procurement.
AB  - Families of potential organ donors might have requests that prolong the donation
      process. Organ procurement organizations therefore should be sensitive to these
      issues, or risk losing potential donors. This study focused on a case that in
      duration surpassed 30 hours from initial referral to cross-clamp in the operating
      room. This article examines the legal, family, and management issues involved in
      such a case.

PMID- 9188363
TI  - Perspectives on communication issues among transplant and procurement
      professionals, transplant recipients, and donor families.
AB  - Communication among professionals, donor families, and transplant recipients is a
      controversial topic. Traditionally, transplant and procurement professionals have
      made the decision about the type and frequency of information that a donor family
      and transplant recipient receive regarding one another, and relationships that
      might develop as a result. Information obtained through questionnaires
      demonstrated inconsistency in addressing donor family and transplant recipient
      needs for initial and follow-up information and communication-not only between
      clinical transplant and procurement donation coordinators, but within
      organizations involved in the care and support of these people. This wide
      variance regarding communication among all disciplines demonstrated a need for
      standardization of practice guidelines. Guidelines are being developed through
      collaboration of the major organizations involved in the care of donor families
      and transplant recipients to standardize communication practices throughout the
      United States.

PMID- 9188364
TI  - The timing factor in the consent process.
AB  - Organ procurement organizations have been educating the medical profession on the
      importance of timing during the donation request process. Separating the request
      for donation from the notification of death has been encouraged when approaching
      families for consent for organ donation. This study evaluated the timing of the
      family approach and consent rates. A 23-month study was performed on all organ
      donor referrals in a 1.1 million population base. During the study period there
      were 203 referrals: 67 were medically unsuitable, next-of-kin was not available
      in 2 cases, 7 were coroner refusals, and 127 were suitable for donation. In this
      latter group, families were offered the option of organ donation. No apparent
      difference when donation was requested before or after the death pronouncement
      was found. Data indicated, however, that when the family is told of the death and
      is asked for donation simultaneously, the consent rate decreases 32% to 37%.

PMID- 9188365
TI  - A continuous quality improvement process to increase organ and tissue donation.
AB  - The Omnibus Budget Reconciliation Act of 1987 mandated that hospitals must
      identify potential organ and tissue donors, notify an organ procurement
      organization of the potential donor, and inform family members regarding the
      opportunity to donate organs and tissues. Although the Joint Commission on
      Accreditation of Healthcare Organizations requires that hospitals comply with
      this statute, no standard for documenting compliance exists. A continuous quality
      improvement process was developed at one institution to define a policy, educate
      staff, and document and monitor compliance. The number of referrals to the organ
      procurement organization and the number of organ and tissue donors were found to
      increase. These observations suggest that implementation of a continuous quality
      improvement process that ensures compliance with organ procurement regulations
      might increase the number of organ and tissue donors.

PMID- 9188366
TI  - Organ donor Care MAP: a multidisciplinary approach.
AB  - A Care Multidisciplinary Action Plan was developed at a 300-bed rural medical
      center in 1994. Once a potential organ donor is identified and referred to the
      organ procurement organization and the family has consented to donation, the ICU
      nurse initiates the Care Multidisciplinary Action Plan, which is based on an 8
      hour time frame for ICU care that may be adjusted as needed. The first hour
      includes prompts for coroner notification, billing changes, and completion of
      hospital-specific death notice forms. The remaining hours are spent administering
      tests and preparing the donor for organ retrieval. Collaborative issues such as
      donor family support also are addressed. ICU nurses who used the donor care
      Multidisciplinary Action Plan were interviewed to determine its effectiveness.

PMID- 9188367
TI  - Public perceptions of an appropriate donor card/brochure.
AB  - Donor card/brochures have not had a major impact on donation, though considerable
      resources have been invested in their development and distribution. One reason
      for this may be that they have not been evaluated by the people expected to sign
      them: the American public. A focus group format was used to develop a
      quantitative survey to assess the public's perception of an appropriate donor
      card/brochure. Several donor card/brochures were studied to compare and evaluate
      their effectiveness, content, format, and acceptance of the message. A donor
      card/brochure was designed that was based on the results of the survey: it
      included a business reply card for further evaluation. The newly developed donor
      card/brochure continues to be viewed positively by those returning business reply
      cards. Most have signed the card and discussed donation with family members.

PMID- 9188368
TI  - Ten years of Orthoclone OKT3 (muromonab-CD3): a review.
AB  - Many important advances in transplantation have been made during the last decade.
      The introduction of Orthoclone OKT3 into clinical trials and its subsequent
      approval by the Food and Drug Administration in 1985 for use as an antirejection
      agent for renal transplantation were landmarks in the field of clinical
      transplantation of solid organs. In the decade since the approval of OKT3 for
      clinical use, much has been learned and written about OKT3. OKT3 now is
      considered a safe and effective agent for prophylaxis and first-line treatment of
      acute rejection of solid organ allografts. In this article, the development and
      use of OKT3 over the last 10 years, as well as the present status and future
      implications of immune therapy with OKT3, are reviewed.

PMID- 9188369
TI  - Use of FK506 immunosuppressive therapy in pancreas transplantation.
AB  - The purpose of this study was to evaluate the safety, efficacy, and transplant
      outcomes associated with FK506 rescue and maintenance therapy in pancreas
      transplant recipients. A chart review was conducted on 10 patients receiving
      FK506 after pancreas transplantation. Transplant outcomes were compared with an
      equivalent group of patients receiving cyclosporine. Medication dose, side
      effects, infections, rejection episodes, glycemic control, and graft survival
      were recorded from 2 to 28 weeks after transplant. Rescue therapy was successful
      in the patients who were converted to FK506 prior to a significant decline in
      glycemic control, whereas those patients who were converted after a decline in
      glycemic control were required to return to exogenous insulin administration.
      Neurological complications, nephrotoxicity, incidence of infection, hypertension,
      rejection, and graft survival were similar for both groups. Use of FK506 is
      comparable to cyclosporine in pancreas allograft recipients and successful
      conversion from cyclosporine to FK506 can be undertaken for rescue therapy.

PMID- 9188370
TI  - The lived experience of end-stage liver failure and liver transplantation.
AB  - This phenomenological study examined the lived experience of an individual who
      underwent end-stage liver failure and liver transplantation. The participant was
      asked to respond to the question, what was it like for you having experienced end
      stage liver failure and liver transplantation? Permission was granted to tape
      record the interview. Themes derived from the data analysis were identified,
      analyzed, and sorted. As a result, four categories were delineated: (1)
      uncertainty, (2) control, (3) social support, and (4) spirituality. Categories
      and themes contributing to a description of one individual's experience with end
      stage liver failure and liver transplantation may provide direction for
      interventional studies designed to effect change in the lived experiences of
      those undergoing similar phenomena.

PMID- 9188371
TI  - Returning to work after liver transplant: experiencing the roadblocks.
AB  - Liver transplant has been the treatment of choice for people with end-stage liver
      disease since the mid-1980s. The theme of returning to work after liver
      transplantation emerged from the data of a phenomenological study examining the
      lived experience of people with liver transplants. Thirteen liver recipients were
      interviewed using a semistructured approach. Only one of the first nine
      participants was able to return to work after the transplant; therefore, the last
      four participants were purposely chosen because they had been able to return to
      work. The possibility of losing health insurance benefits and disability benefits
      prevented many participants from working. Those able to return to work had
      professional careers that afforded them flexibility in their work schedule. Some
      implications for health professionals lie in the area of healthcare and health
      insurance policy change. Avenues for health insurance reform could be explored in
      an effort to empower the transplant recipient.

PMID- 9188372
TI  - Nurse management of posttransplant hypertension in liver transplant patients.
AB  - Hypertension develops soon after organ transplantation using cyclosporine- or
      FK506-based immunosuppression. Sustained rises in blood pressure require
      intervention to reduce the risk of intracranial bleeding and other cardiovascular
      complications. Antihypertensive treatment is complicated by reduced renal
      function and potential interference with absorption and/or metabolism of
      cyclosporine or FK506. To manage early and long-term hypertension related to
      immunosuppression with cyclosporine or FK506 and prednisone following orthotopic
      liver transplantation, a comprehensive nurse-managed hypertension clinic was
      developed. Blood pressure, heart rate, and antihypertensive and immunosuppressive
      regimens were evaluated according to a standard protocol at 1, 4, 12, 24, and 36
      months after orthotopic liver transplantation. Data indicate that
      posttransplantation hypertension develops within the first months after
      orthotopic liver transplantation and persists indefinitely. If comprehensively
      managed by the hypertension nurse-clinician, the percentage of controlled
      hypertension patients can increase over time.

PMID- 9188373
TI  - Liver transplantation for hepatocellular carcinoma: one center's experience, 1987
      1994.
AB  - A retrospective review was done to evaluate the detection of hepatocellular
      carcinoma preoperatively, using ultrasonography and alpha-fetoprotein in patients
      awaiting orthotopic liver transplantation. Sixteen of the 187 patients who
      underwent 209 orthotopic liver transplantations at the Ochsner Transplant Center
      from 1987 to 1994 were diagnosed with hepatocellular carcinoma, 3 preoperatively
      and 11 at the time of pathological inspection of the liver explant. Two developed
      metastatic hepatocellular carcinoma while awaiting orthotopic liver
      transplantation. Ultrasonography detected abnormalities in the region where
      hepatoma was identified in 5 of 11 (45%) patients with incidental hepatocellular
      carcinoma, in all 3 with overt hepatocellular carcinoma, and in neither of the 2
      who developed metastatic hepatocellular carcinoma while awaiting orthotopic liver
      transplantation. Hepatocellular carcinoma was present in 5 of 23 (22%) patients
      with an alpha-fetoprotein greater than 20 ng/mL and in 3 of 10 (30%) with an
      alpha-fetoprotein greater than 50 ng/mL.

PMID- 9188374
TI  - Considerations for using ketoconazole in solid organ transplant recipients
      receiving cyclosporine immunosuppression.
AB  - Drug interactions involving cyclosporine following transplantation are a
      challenging issue for the transplant clinician. This is especially true when
      ketoconazole is the second agent used in conjunction with cyclosporine. Because
      both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system,
      cyclosporine levels rise dramatically in the presence of ketoconazole. Many other
      agents interact with ketoconazole, either by competitive enzyme inhibition in the
      liver and gastrointestinal tract, or by reducing the absorption of ketoconazole
      by agents that increase the pH of the gastrointestinal tract. Despite the
      potential cost savings when using ketoconazole to reduce cyclosporine doses,
      adverse effects associated with ketoconazole put patients at risk when using this
      combination. Close monitoring of cyclosporine levels is imperative when adding
      ketoconazole to cyclosporine, and once the dosage adjustments are complete, the
      addition of a third drug that interacts with either cyclosporine or ketoconazole
      could result in an unexpected rejection episode or toxic cyclosporine side
      effect.

PMID- 9188375
TI  - Relationship between donor/recipient lung size mismatch and functional outcome in
      single lung transplantation for COPD.
AB  - Single lung transplantation is an effective treatment for patients with severe
      chronic obstructive pulmonary disease. Pulmonary hyperinflation, which is seen in
      most patients with severe chronic obstructive pulmonary disease, makes the task
      of appropriately matching the donor and recipient difficult. It seems that the
      optimal matching strategy remains undefined. No correlation between
      donor/recipient size match (actual and predicted) and the degree of functional
      improvement after single lung transplantation was found. There were no
      significant differences noted when comparing the functional outcomes of right and
      left lung transplant recipients. It was concluded that the chronic hyperinflation
      associated with severe chronic obstructive pulmonary disease allows for the use
      of significantly larger donors. The use of expanded donor/recipient size match
      criteria in patients with severe chronic obstructive pulmonary disease may
      shorten the waiting period prior to single lung transplantation and provide
      better utilization of donor organs.

PMID- 9188376
TI  - Research: a process for pioneers.

PMID- 9188377
TI  - Transplantation in Italy.
AB  - Organ procurement and transplantation have been difficult in Italy for many
      years. However, recent initiatives at the organizational level led to the
      establishment of the National Reference Centre, which is working hard to
      accomplish its tasks. We describe the transplantation activity of the past 2
      years, which shows an improved situation that is encouraging. We include a brief
      history on transplantation in Italy and give some information to enhance
      understanding of the changes that have occurred and their impact on
      transplantation.

PMID- 9188378
TI  - Evaluation of a small organ procurement organization in the Basque country,
      Spain.
AB  - A limited supply of organs is the main obstacle for organ transplantation. The
      shortage reflects not only a shortage of donors but also a failure to make use of
      existing donors. The Basque Country Transplant Coordination Team is an organ
      procurement organization that operates in the Basque country, an area of 7260 km2
      with 2.1 million inhabitants. From January 1, 1990, to December 31, 1995, the
      number of potential cadaveric organ donors found by the team increased, to 70
      donors per million inhabitants in 1995. Since 1993, the organization has had more
      than 30 donors per million persons and has procured more than 90 cadaveric
      organs, including more than 60 cadaveric kidneys, per million persons. Because of
      these rates, the team coordinated 61.7 cadaveric kidney transplants per million
      persons during 1995. This paper describes some characteristics of the Basque
      organ procurement organization that might explain these results.

PMID- 9188379
TI  - Age: an indicator of willingness to donate?
AB  - Answers to the question about consent for organ donation on the Queensland
      Transport Driver's Licence Database were reviewed to determine if age is an
      indicator of willingness to donate. As of November 1994, the database contained
      records on 1,969,382 persons (54% male, 46% female), accounting for 86.7% of the
      population 17 years of age or older. Fifty-four percent had answered yes to the
      question; 46% had indicated no or had not answered. The data were divided into
      three groups, males only, females only, and males plus females, and then
      subgrouped by age. The number of subjects who had not answered the question was
      included in the number who had answered no. In the males-plus-females group, the
      percentage of yes answers by age remained relatively constant (56%-62%) for
      persons 17 to 49 years old but decreased to 39% for persons 70 years old. The
      data for males only and females only showed a similar decrease. Slightly more
      females than males had answered yes among persons 17 to 49 years old (mean
      difference, 5%; range, 1%-8%). This difference decreased with age. A higher
      willingness to donate in the younger age groups may augur well for the future.
      The data indicate that more attention must be given to persons 50 years of age
      and older to increase their awareness of their ability to donate.

PMID- 9188380
TI  - The relative impact of presumed-consent legislation on thoracic organ donation in
      the Eurotransplant area.
AB  - A country's organ donation rate and hence the availability of thoracic organs can
      be increased by organizational measures, by legislative incentives, and by
      increasing awareness among the public and healthcare professionals. We analyzed
      the relative impact of organ procurement legislation or policy on heart and lung
      donation rates per million population per year in the four countries
      participating in the Eurotransplant organization (population, 112.7 million)
      between January 1992 and December 1994. Within this organization, Austria and
      Belgium have presumed-consent legislation, whereas Germany and the Netherlands
      have an opting-in (explicit-consent) policy. Although practices vary even among
      countries with similar policies (eg. in Belgium, relatives of the donor retain
      the right to object to procurement of organs in the absence of an explicit
      consent from the deceased before death), rates of heart and lung donation were at
      least twice as high in the two countries with presumed-consent legislation as in
      the two countries that rely on a policy of explicit consent from the donor's next
      of kin.

PMID- 9188381
TI  - Risk factors for premature coronary heart disease after successful liver
      transplantation in adults.
AB  - As solid-organ transplantation has evolved into a highly effective treatment for
      end-stage organ disease, the long-term health implications of chronic exposure of
      recipients to immunosuppressants and other pharmacological agents are becoming
      more apparent. Coronary heart disease has long been known to plague kidney
      transplant recipients and more recently has been found to affect heart transplant
      recipients disproportionately. Coronary heart disease after liver
      transplantation, however, is less well known. The purpose of this study was to
      examine risk factors for premature coronary heart disease in asymptomatic adult
      recipients of liver transplants. Nutrition-related risk factors for coronary
      heart disease (obesity and hyperlipidemia) were measured in 29 patients before
      and after liver transplantation. Changes with respect to primary
      immunosuppression protocol (cyclosporine plus corticosteroid vs tacrolimus plus
      corticosteroid) were compared. Risk factors that had not been present before
      transplantation were apparent in both groups by 6 months after transplantation.
      Although obesity and hyperlipidemia were not found to be independent risk factors
      for coronary heart disease, they were clinically important when considered in
      combination. Cyclosporine was associated with significantly higher serum lipid
      concentrations than was tacrolimus.

PMID- 9188382
TI  - Religious attitudes regarding organ donation.
AB  - This study of seminary students, religious leaders, and hospital chaplains
      illustrates the importance of educating clergy about organ donation. Religious
      objections are often cited as a reason for refusal to give consent for donation.
      Results of this study show that most clergy are supportive of organ donation.
      However, the survey pointed out some misunderstanding of the concept of brain
      death. Thus, although the clergy are supportive and influential, they tend not to
      receive medical information that is key to the donation process. Further
      education specifically focused on religious leaders is needed.

PMID- 9188383
TI  - Interaction of organ donor families and recipients.
AB  - An exploratory descriptive study of donor families and recipients of cadaveric
      organs was done to determine their feelings about direct contact with each other.
      Direct contact was desired by 70% of donor families and 75% of recipients. Donor
      families wanted to see firsthand the benefit of the transplant to another person.
      Recipients primarily wanted to express gratitude. Both groups think they have a
      right to meet. Although both think these interactions should be professionally
      regulated and facilitated, they do not think the transplant center or the organ
      procurement organization is responsible for the outcome of a meeting. Donor
      families and recipients think the process should be gradual with prior
      correspondence. On the basis of our findings, we have developed a list of
      suggested guidelines to use when facilitating an interaction.

PMID- 9188384
TI  - Twelve years' experience with non-heart-beating cadaveric donors.
AB  - From 1983 to August 1995, the University of Miami Organ Procurement Organization
      evaluated 41 candidates for non-heart-beating cadaveric donation and determined
      that 34 patients met the criteria. All patients had irreversible brain injury
      incompatible with survival. All families gave permission for withdrawal of life
      support and for tissue and organ donation after cardiac arrest. Thirteen donors
      died in the operating room, and 9 died in the ICU or emergency department. Four
      of the 9 patients who died in the ICU had undergone femoral cannulation. The
      remaining 12 donors were brain-dead but had an unpredicted cardiac arrest before
      laparotomy. All kidneys were preserved by using machine pulsatile perfusion, and
      21 kidneys were transported to other centers. Of the 35 transplanted kidneys, 26
      (74%) had immediate function, 6 (17%) had delayed graft function, and 3 (9%) were
      not used for other reasons. Five of the six transplanted livers had immediate
      function.

PMID- 9188385
TI  - The case against more public education to promote organ donation.
AB  - The organ procurement community has always considered public education a primary
      challenge. According to conventional wisdom, greater awareness generated by
      public education will lead to more donated organs. This notion may be based on
      faulty assumptions about public education and about the relationship between
      awareness and behavior. Public education, as the primary focus for the organ
      procurement community, should be abandoned. Increased efforts in professional
      education and basic research are more appropriate endeavors for organ procurement
      organizations.

PMID- 9188386
TI  - Planning and implementing a research project: Part 1.
AB  - This article is the first in a series of three focused on the steps in the
      development of a research proposal. This first article presents the beginning
      steps of identification of a problem, statement of the research question and
      hypotheses, and review of the literature. The series of articles is meant to
      provide an overview of how to accomplish each of the steps. The discussion of the
      steps focuses the reader on helpful hints pertinent to each step. Additional
      references are provided for a more in-depth discussion of the process.

PMID- 9188387
TI  - Certification of transplant coordinators by the American Board of Transplant
      Coordinators.
AB  - Voluntary certification of transplant coordinators has taken place in the United
      States since 1988 and has operated under the auspices of the American Board of
      Transplant Coordinators since its formation in 1987. This article reviews the
      rationale for development of a certification process, how the examinations were
      developed and are updated, eligibility to take the examination, and relationship
      with standards of practice for transplant coordinators.

PMID- 9188388
TI  - Effect of use of vasopressors in organ donors on immediate function of renal
      allografts.
AB  - The purpose of this study was to determine whether use of vasopressors in
      cadaveric donors of renal transplants was associated with an increased prevalence
      of acute tubular necrosis after kidney transplantation. We compared immediate
      allograft function in 26 consecutive renal allograft recipients whose donors had
      been given vasopressors with that in 26 recipients whose donors had nor. The
      donors treated with vasopressors had been given more than 10 micrograms/kg per
      minute of dopamine, norepinephrine, or epinephrine, alone or in combination. The
      groups were matched with respect to donors' age, recipients' disease, and cold
      ischemic time. The prevalence of immediate allograft function was significantly
      lower in recipients whose donors had required use of vasopressors (38.5%) than in
      recipients whose donors had not required vasopressors (65.4%). We conclude that
      use of vasopressors in kidney donors leads to an increased prevalence of acute
      tubular necrosis.

PMID- 9188389
TI  - 21st annual meeting, North American Transplant Coordinators Organization--San
      Diego, August 7, 1996.

PMID- 9188390
TI  - Transplantation for borderline candidates: lifeboat or Titanic?

PMID- 9188391
TI  - The case against more public education to promote organ donation.

PMID- 9188392
TI  - The case against more public education to promote organ donation.

PMID- 9188393
TI  - The impact of a comprehensive, hospital-focused intervention to increase organ
      donation.
AB  - In this article the results of a 2-year intervention designed to increase rates
      of organ donation while improving services to bereaved families of potential
      donors are described. The project focused on improving key elements of the organ
      donation process. The intervention was implemented in 50 hospitals within the
      service areas of three organ procurement organizations. Results show an increase
      in identification, referral, and asking rates. The overall donation rate
      increased significantly, from 33% to 43%. However, consent rates remained
      unchanged. Future efforts should focus on improving the request process by
      systematically incorporating practices that are associated with higher consent
      rates. This should enable hospital and organ procurement organization staff to
      appropriately and effectively offer families the option of organ donation;
      further increases in organ donation should follow.

PMID- 9188394
TI  - Explaining brain death: a critical feature of the donation process.
AB  - To examine how a family's understanding of brain death may affect the decision to
      donate, an interview study was conducted with the immediate next of kin of 164
      medically suitable organ donor candidates. Telephone interviews were conducted
      with members of both donor and nondonor families 4 to 6 months after the
      relative's death. Only 61% of the donor and 53% of the nondonor respondents said
      they had received an explanation of brain death. Few respondents reported that
      the hospital or organ procurement organization staff used visual aids to clarify
      or reinforce the information they were given. Next of kin who decided against
      donation had far less understanding of brain death than did those who decided in
      favor of it. Before making an organ donation request, healthcare providers must
      inquire about and address common misunderstandings people have about brain death.
      Healthcare teams should develop and be trained on a clear protocol for
      communicating with the families of patients who may be potential organ donors.

PMID- 9188395
TI  - Strategies for success among OPOs: a study of three organ procurement
      organizations.
AB  - Productivity among organ procurement organizations varies widely in the US, and
      the pressure to determine critical success factors increases as the organ pool
      shrinks and managed care expands. This study compared three successful organ
      procurement organizations, identified commonalities among them in cost of doing
      business, and examined direct and indirect expenses, staffing, specialized
      requestor programs, and professional and public education programs. The three
      organ procurement organizations were chosen because of their performance in terms
      of donors per million population, complexity, and size. The following key
      indicators were compared and analyzed: annual operating budget, size and
      composition of staff, funds and resources invested in professional education
      versus public education, tissue recovery operations, results of minority
      initiatives, and employee compensation programs.

PMID- 9188396
TI  - Procurement coordinator support group.
AB  - This article describes a support group for procurement coordinators. The group
      was initiated to help coordinators assist grieving donor families and to cope
      with their own reactions to stressful events. The theory underlying support
      groups is presented as a guide to understanding the purpose and process of the
      group. Issues of concern to coordinators are discussed along with strategies for
      facilitating group discussions and reducing stress.

PMID- 9188397
TI  - Stress and coping among parents of children awaiting cardiac transplantation.
AB  - Psychosocial support during the waiting period for pediatric transplant
      recipients and their families is vital. This study describes the stress levels
      and coping techniques among parents of children awaiting cardiac transplant.
      Twenty-six parents of 18 children demonstrated a range of stress with 77% scoring
      at a moderate stress level. They perceived transplantation neutrally and used a
      similar number of coping mechanisms as did a normative group of adults. Use of
      coping mechanisms significantly decreased over the 3-month study period. A
      moderate correlation between a negative perception of transplantation and
      parental stress was found. Parents of girls viewed transplant more negatively
      than did boys' parents. This study provides a beginning for assisting families
      during the waiting period.

PMID- 9188398
TI  - Considerations in presenting, interpreting, and reviewing research findings.
AB  - By disseminating reports of well-conducted research in peer-reviewed journals,
      investigators regularly provide valuable information and insights to other
      professionals. Prospective authors of such reports should be aware that submitted
      manuscripts undergo considerable scrutiny and analysis by reviewers and editors
      as part of the publication cycle and, later, by readers for whom the information
      is intended. Therefore, when a researcher becomes an author, he or she should
      attempt to be as complete as possible in meeting the needs of those audiences. In
      this article, we discuss problems often found in research reports submitted to
      peer-reviewed journals so that investigators may improve the quality of their
      manuscripts.

PMID- 9188399
TI  - Practising defensively.

PMID- 9188400
TI  - Dental advice for mothers and infants.

PMID- 9188401
TI  - Humour in midwifery.

PMID- 9188402
TI  - CESDI: a review.

PMID- 9188403
TI  - The midwife's duty of care.

PMID- 9188404
TI  - Clinical guidelines for the management of women.

PMID- 9188407
TI  - All change.

PMID- 9188408
TI  - Lorna Muirhead. Interview by Matthew Pulzer.

PMID- 9188409
TI  - The NBNI. National Board for Nursing, Midwifery and Health Visiting for Northern
      Ireland.

PMID- 9188410
TI  - Promises, promises.

PMID- 9188411
TI  - Come the devolution....

PMID- 9188413
TI  - The same, but different.

PMID- 9188412
TI  - A fair share of care.

PMID- 9188414
TI  - Nursing students can now acquire clinical skills in community psychiatry.

PMID- 9188415
TI  - Front page splash. Interview by Richard Morris.

PMID- 9188416
TI  - Nurses flex their industrial muscle.

PMID- 9188417
TI  - Crowning the campaign.

PMID- 9188418
TI  - Novel pursuits. Interview by Christina Bunce.

PMID- 9188419
TI  - Forging new roles.

PMID- 9188420
TI  - Juvenile chronic arthritis: epidemiology and genetics.
AB  - This article looks at the classification, epidemiology and possible causes of
      juvenile chronic arthritis. The clinical manifestations of the different types of
      this disease are discussed. Finally the course and prognosis of this disease are
      described. A second article on juvenile chronic arthritis will appear on May 28
      1997.

PMID- 9188421
TI  - How rheumatoid arthritis affects patients and families.
AB  - This article looks at the social problems of adults with rheumatoid arthritis.
      The effects on the family and children are discussed along with the role
      responsibilities. The role of the nurse in relation to patients and their family
      is illustrated.

PMID- 9188422
TI  - Systematic reviews: what do they involve?
AB  - Systematic reviews are a source of evidence to guide practice and identify the
      need for future research. This article gives an outline of the methods involved
      in conducting systematic reviews, including the identification of a review topic,
      searching literature, selecting studies to be reviewed and synthesising study
      findings.

PMID- 9188423
TI  - Theophylline in acute childhood asthma.

PMID- 9188424
TI  - Home is where the heart is.

PMID- 9188426
TI  - Managing the risk.

PMID- 9188425
TI  - Primary care and mental health problems.

PMID- 9188427
TI  - People with Lassa fever. Interview by Anne Gulland.

PMID- 9188429
TI  - Older and wiser, but does anyone care?

PMID- 9188428
TI  - Pay and concessions.

PMID- 9188430
TI  - Delivering satisfaction.

PMID- 9188431
TI  - For immediate topical application.

PMID- 9188432
TI  - When views of care conflict.

PMID- 9188433
TI  - Realm of the senses.

PMID- 9188434
TI  - R&D priorities.

PMID- 9188435
TI  - Asthma in older people.

PMID- 9188436
TI  - Behavioural misdiagnosis.
AB  - This article explores the possibility that the behaviours of some clients with
      learning disabilities may be due to neurological dysfunction. It outlines some
      neurological explanation for behaviour previously labelled as challenging, and
      observes how this knowledge may affect our common understanding of people with
      learning disabilities.

PMID- 9188438
TI  - How to avoid the pitfalls of questionnaire design.
AB  - This article discusses how questionnaires are constructed and used. Question
      choice and construction plus the allocation of codes to analyse answers are
      discussed. A second article on this subject, due to appear in Nursing Times on
      June 4, will examine questionnaire layout, issues of reliability and validity and
      questionnaire piloting.

PMID- 9188439
TI  - Diphtheria: a changing pattern.

PMID- 9188437
TI  - Evaluation of nurse and midwife education in Scotland.
AB  - The authors of an evaluation of the new programmes of nurse and midwife education
      in Scotland summarise their findings and methods. Students were found to be
      enjoying rich educational experiences. However, they did identify a number of
      problems in initial programme development, achievement of student roles and in
      assessment of learning. The authors offer recommendations for continued
      curriculum development and for further research. The evaluation was commissioned
      by the National Board for Scotland.

PMID- 9188440
TI  - Now, wash your hands please.

PMID- 9188441
TI  - New developments in phospholipase D.

PMID- 9188442
TI  - Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and
      caveolin.
AB  - The endothelial nitric-oxide synthase (eNOS) is a key determinant of vascular
      homeostasis. Like all known nitric-oxide synthases, eNOS enzyme activity is
      dependent on Ca2+-calmodulin. eNOS is dynamically targeted to specialized cell
      surface signal-transducing domains termed plasmalemmal caveolae and interacts
      with caveolin, an integral membrane protein that comprises a key structural
      component of caveolae. We have previously reported that the association between
      eNOS and caveolin is quantitative and tissue-specific (Feron, O., Belhassen, L.,
      Kobzick, L., Smith, T. W., Kelly, R. A., and Michel, T. (1996) J. Biol. Chem.
      271, 22810-22814). We now report that in endothelial cells the interaction
      between eNOS and caveolin is importantly regulated by Ca2+-calmodulin. Addition
      of calmodulin disrupts the heteromeric complex formed between eNOS and caveolin
      in a Ca2+-dependent fashion. In addition, overexpression of caveolin markedly
      attenuates eNOS enzyme activity, but this inhibition is reversed by purified
      calmodulin. Caveolin overexpression does not affect the activity of the other NOS
      isoforms, suggesting eNOS-specific inhibition of NO synthase by caveolin. We
      propose a model of reciprocal regulation of eNOS in endothelial cells wherein the
      inhibitory eNOS-caveolin complex is disrupted by binding of Ca2+-calmodulin to
      eNOS, leading to enzyme activation. These findings may have broad implications
      for the regulation of Ca2+-dependent signal transduction in plasmalemmal
      caveolae.

PMID- 9188443
TI  - Protein splicing of the Saccharomyces cerevisiae VMA intein without the
      endonuclease motifs.
AB  - The protein splicing element (intein) of the vacuolar ATPase subunit (VMA) of
      Saccharomyces cerevisiae catalyzes both protein splicing and site-specific DNA
      cleavage. It has been demonstrated that the conserved splice junction residues
      are directly involved in protein splicing and the central dodecapeptide motifs
      are required for DNA cleavage. To examine whether the splicing activity of the
      intein can be structurally separated from the endonuclease motifs, we made large
      in-frame deletions at the central region of the intein. We demonstrate for the
      first time that protein splicing can proceed efficiently after the removal of the
      central region of the intein including the endonuclease motifs. Our results
      suggest that the N- and C-terminal regions of the Sce VMA intein may form a
      separate domain that is not only catalytically sufficient for protein splicing
      but also structurally independent from the endonuclease domain.

PMID- 9188444
TI  - Farnesyltransferase inhibitors alter the prenylation and growth-stimulating
      function of RhoB.
AB  - Protein farnesyltransferase inhibitors (FTIs) inhibit Ras transformation and Ras
      dependent tumor cell growth, but the biological mechanisms underlying these
      activities is unclear. In previous work, we presented support for the hypothesis
      that the anti-transforming effects of FTIs depend upon alterations in the
      function of RhoB, a member of the Rho family of proteins that regulate
      cytoskeletal actin, cell adhesion, and cell growth. A significant question that
      needed to be addressed was whether FTIs could directly alter the prenylation as
      well as the function of RhoB in cells. This issue is complex because farnesylated
      and geranylgeranylated forms of RhoB (RhoB-F and RhoB-GG) both exist in cells.
      Here, we show that RhoB farnesylation in vitro can be catalyzed by protein
      farnesyltransferase and that the peptidomimetic FTI L-739,749 inhibits the
      farnesylation of RhoB both in vitro and in intact cells. In drug-treated cells,
      the level of RhoB-GG increased in parallel with the decrease in RhoB-F. In
      addition to altering RhoB prenylation, L-739,749 suppressed RhoB-dependent cell
      growth. Taken together, the results suggest that the inhibitory effects of FTIs
      on RhoB function can be mediated by a relative loss of RhoB-F, a gain of RhoB-GG,
      or both. Our findings strengthen the causal link between RhoB inhibition and the
      anti-transforming effects of FTIs and indicate that differently prenylated forms
      of RhoB may have unique functions.

PMID- 9188445
TI  - Transphosphorylation of Bruton's tyrosine kinase on tyrosine 551 is critical for
      B cell antigen receptor function.
AB  - Bruton's tyrosine kinase (Btk) is required for B cell development and B cell
      antigen receptor (BCR) function. Cross-linking of BCR induces phosphorylation of
      Btk at Tyr551 and Tyr223. However, the functional requirement of these
      phosphorylation for BCR signaling remains unclear. We demonstrate here that
      mutation of Tyr551, not Tyr223, abrogates the BCR-induced calcium mobilization.
      Not only Lyn, but also Syk was required for tyrosine phosphorylation of Btk in
      BCR signaling. These results suggest that transphosphorylation of Btk on Tyr551
      is essential for BCR function and that this phosphorylation is mediated through
      the concerted actions of Lyn and Syk.

PMID- 9188446
TI  - A point mutation of human nucleoside diphosphate kinase A found in aggressive
      neuroblastoma affects protein folding.
AB  - The point mutation serine 120 to glycine in the human nucleoside diphosphate
      kinase A has been identified in several aggressive neuroblastomas (Chang, C. L.,
      Zhu, X. X., Thoraval, D. H., Ungar, D., Rawwas, J., Hora, N., Strahler, J. R.,
      Hanash, S. M. & Radany, E. (1994) Nature 370, 335-336). We expressed in bacteria
      and purified wild-type and S120G mutant nucleoside diphosphate kinase A. The
      mutant enzyme had enzymatic and structural properties similar to the wild-type
      enzyme, whereas its stability to denaturation by heat and urea was markedly
      reduced. More importantly, upon renaturation of the urea-denatured mutant
      protein, a folding intermediate accumulated, having the characteristics of a
      molten globule. It had no tertiary structure, as shown by near UV circular
      dichroism, whereas the secondary structure was substantially recovered. The
      hydrophobic probe 8-anilino-1-naphthalene sulfonate bound to the intermediate
      species with an increase in fluorescence intensity and a blue shift. The
      hydrodynamic size was between that expected for a folded and an unfolded monomer.
      Finally, electrophoresis in a transverse urea gradient displayed no renaturation
      curve, and the protein showed the tendency to aggregate at the lowest urea
      concentrations. The existence of a molten globule folding intermediates resulting
      from an altered folding in the mutated protein might be related to the
      aggressiveness of neuroblastomas.

PMID- 9188447
TI  - Conformational selectivity of HIV-1 protease cleavage of X-Pro peptide bonds and
      its implications.
AB  - Kinetic measurements on a fluorescent peptide analog of the p17/p24 cleavage site
      of the Gag polyprotein demonstrate the conformational selectivity of human
      immunodeficiency virus, type 1 protease for the trans conformation of the Tyr-Pro
      bond. A mean cis/trans ratio of 0. 3, and a cis --> trans isomerization rate
      constant of 0.022 s-1 are determined at T = 22 degrees C. This rate is in
      excellent agreement with that predicted by 19F NMR studies of structurally
      analogous peptides containing a fluorine/hydroxyl substitution on the tyrosyl
      residue. Addition of recombinant human cyclophilin resulted in a significant
      enhancement of this rate, and it is proposed that this enzyme, which has been
      shown to be associated with the Gag protein, functions as an auxiliary enzyme for
      the protease during cleavage in the virion.

PMID- 9188448
TI  - Chaperone properties of the bacterial periplasmic substrate-binding proteins.
AB  - Bacterial periplasmic substrate-binding proteins are initial receptors in the
      process of active transport across cell membranes and/or chemotaxis. Each of them
      binds a specific substrate (e.g. sugar, amino acid, or ion) with high affinity.
      For transport, each binding protein interacts with a cognate membrane complex
      consisting of two hydrophobic proteins and two subunits of a hydrophilic ATPase.
      For chemotaxis, binding proteins interact with specific membrane chemotaxis
      receptors. We report, herewith, that the oligopeptide-binding protein OppA of
      Escherichia coli, the maltose-binding protein MalE of E. coli, and the galactose
      binding protein MglB of Salmonella typhimurium interact with unfolded and
      denatured proteins, such as the molecular chaperones that are involved in protein
      folding and protein renaturation after stress. These periplasmic substrate
      binding proteins promote the functional folding of citrate synthase and alpha
      glucosidase after urea denaturation. They prevent the aggregation of citrate
      synthase under heat shock conditions, and they form stable complexes with several
      unfolded proteins, such as reduced carboxymethyl alpha-lactalbumin and unfolded
      bovine pancreatic trypsin inhibitor. These chaperone-like functions are displayed
      by both the liganded and ligand-free forms of binding proteins, and they occur at
      binding protein concentrations that are 10-100-fold lower than their periplasmic
      concentration. These results suggest that bacterial periplasmic substrate-binding
      proteins, in addition to their function in transport and chemotaxis, might be
      implicated in protein folding and protection from stress in the periplasm.

PMID- 9188449
TI  - CD86 (B7-2) on human B cells. A functional role in proliferation and selective
      differentiation into IgE- and IgG4-producing cells.
AB  - Immunoglobulin (Ig) E production by B cells requires two primary signals provided
      by T cells, interleukin (IL)-4 or IL-13 and CD40 ligand (CD40L). In addition,
      costimulatory signals, such as CD23-CD21 interaction, contribute further ensuring
      a selective control over this production. Recently, CD28, expressed on T cells,
      has been reported to be involved in this process. The CD28 ligands, CD80 (B7-1)
      and CD86 (B7-2), are expressed on human tonsillar B cells, and their expression
      is up-regulated by IL-4, IL-13, and/or an anti-CD40 monoclonal antibody (mAb). We
      have investigated whether signaling via the B7 molecules affects IgE synthesis.
      Human B cells were stimulated by IL-4 plus anti-CD40 mAb in the presence of
      different anti-B7 mAbs. Cross-linking of CD86 with IT2.2 potentiated IgE and IgG4
      production and epsilon transcripts expression. The production of the other
      isotypes was not modulated. Conversely, the anti-CD80 and the other anti-CD86
      mAbs tested had no effect. The increase of IgE and IgG4 production induced by
      IT2.2 was accompanied by an increase in proliferation, in cell surface density of
      CD23, and in CD23 binding to CD21-expressing B cells. In contrast, the expression
      of other B cell surface molecules such as CD11a, CD30, and CD58 remained
      unaffected. Since IT2.2 favors CD23-CD21 pairing, we tested whether blocking this
      interaction affected IT2.2-increased IgE production. The neutralizing anti-CD23
      mAb, Mab 25, caused a dose-dependent inhibition of the effect of IT2.2 on IgE
      synthesis. Finally, IT2.2 potentiation on B cell proliferation and IgE production
      required the two primary signals, IL-4 and anti-CD40 mAb, since IT2.2 alone or in
      combination with only one of these stimuli did not show any effect on B cells.
      This study is the first demonstration of a signaling role for CD86. Together with
      IL-4 or IL-13 and CD40L, CD86 favors CD23-CD21 pairing and consequently functions
      as a selective and potent costimulus for human IgE and IgG4 synthesis.

PMID- 9188450
TI  - Y13C Azotobacter vinelandii ferredoxin I. A designed [Fe-S] ligand motif contains
      a cysteine persulfide.
AB  - Ferredoxins that contain [4Fe-4S]2+/+ clusters often obtain three of their four
      cysteine ligands from a highly conserved CysXXCysXXCys sequence motif. Little is
      known about the in vivo assembly of these clusters and the role that this
      sequence motif plays in that process. In this study, we have used structure as a
      guide in attempts to direct the formation of a [4Fe-4S]2+/+ in the [3Fe-4S]+/0
      location of native (7Fe) Azotobacter vinelandii ferredoxin I (AvFdI) by providing
      the correct three-dimensional orientation of cysteine ligands without introducing
      a CysXXCysXXCys motif. Tyr13 of AvFdI occupies the position of the fourth
      ligating cysteine in the homologous and structurally characterized 8Fe ferredoxin
      from Peptococcus aerogenes and a Y13C variant of AvFdI could be easily modeled as
      an 8Fe protein. However, characterization of purified Y13C FdI by UV-visible
      spectra, circular dichroism, electron paramagnetic resonance spectroscopies, and
      by x-ray crystallography revealed that the protein failed to use the introduced
      cysteine as a ligand and retained its [3Fe-4S]+/0 cluster. Further,
      electrochemical characterization showed that the redox potential and pH behavior
      of the cluster were unaffected by the substitution of Tyr by Cys. Although Y13C
      FdI is functional in vivo it does differ significantly from native FdI in that it
      is extremely unstable in the reduced state possibly due to increased solvent
      exposure of the [3Fe-4S]0 cluster. Surprisingly, the x-ray structure showed that
      the introduced cysteine was modified to become a persulfide. This modification
      may have occurred in vivo via the action of NifS, which is known to be expressed
      under the growth conditions used. It is interesting to note that neither of the
      two free cysteines present in FdI was modified. Thus, if NifS is involved in
      modifying the introduced cysteine there must be specificity to the reaction.

PMID- 9188451
TI  - The anodic hemoglobin of Anguilla anguilla. Molecular basis for allosteric
      effects in a root-effect hemoglobin.
AB  - The functional and structural basis for the Root effect has been investigated in
      the anodic hemoglobin of the European eel, Anguilla anguilla. This hemoglobin
      exhibits a large Bohr effect, which is accounted for by oxygen-linked binding of
      seven to eight protons in the presence of GTP at pH 7.5. Oxygen equilibrium
      curves show nonlinear lower asymptote of Hill plots, indicating the occurrence of
      heme-heme interactions within the T state. Analysis of the curves according to
      the co-operon model (Brunori, M., Coletta, M., and Di Cera, E. (1986) Biophys.
      Chem. 23, 215-222) reveals that T state cooperativity is positive at high pH and
      in the stripped hemoglobin (where the T --> R allosteric transition is operative)
      and negative at low pH and in the presence of organic phosphate (where the
      molecule is locked in the low affinity structure), indicating site heterogeneity.
      The complete amino acid sequence of eel anodic hemoglobin has been established
      and compared with that of other fish hemoglobins. The presence of the Root effect
      correlates with a specific configuration of the alpha1beta2 switch interface,
      which at low pH would stabilize subunit ligation in the T state without changing
      the quaternary structure. We propose that the major groups involved in the
      binding of oxygen-linked protons in eel anodic hemoglobin are located on the beta
      chain and comprise His-HC3 at the C terminus, His-FG4 at the switch interface,
      and Lys-EF6 and the N terminus at the phosphate-binding site.

PMID- 9188452
TI  - Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B
      cells. A role for p59(Fyn) and SHP2.
AB  - Engagement of beta1 integrins in terminally differentiated human B cell lines,
      such as ARH-77, leads to prominent tyrosine phosphorylation of the p130 Crk
      associated substrate (Cas). Cas regulates the assembly of several SH2 and SH3
      domain-containing proteins into signaling complexes, which are potentially
      involved in the propagation of downstream signals. We demonstrate here that
      immunoprecipitated Cas from beta1 integrin-stimulated ARH-77 cells was associated
      with tyrosine kinase and phosphatase activities and that integrin ligation led to
      the recruitment of at least p59(Fyn) tyrosine kinase and SHP2 tyrosine
      phosphatase in Cas immune complexes. Cotransfection studies in COS-7 cells
      further indicated that Fyn/Cas physical interaction and Fyn-mediated Cas
      phosphorylation required amino acids 638-889 in the C-terminal region of Cas.
      This sequence contains both c-Src SH2 and SH3 domain-binding motifs. In vitro
      binding studies using glutathione S-transferase fusion proteins derived from the
      SH2 or SH3 domains of Fyn suggested that both Fyn domains can participate in
      Fyn/Cas interaction. These data implicate Fyn and SHP2 as potential modulators of
      Cas signaling complexes in B cells.

PMID- 9188453
TI  - Redox-regulated signaling by lactosylceramide in the proliferation of human
      aortic smooth muscle cells.
AB  - Previously, our laboratory reported that lactosylceramide (LacCer) stimulated
      human aortic smooth muscle cell proliferation via specific activation of p44
      mitogen-activated protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and
      induced expression of the transcription factor c-fos downstream to the p44 MAPK
      signaling cascade (Bhunia A. K., Han, H., Snowden, A., and Chatterjee S. (1996)
      J. Biol. Chem. 271, 10660-10666). In the present study, we explored the role of
      free oxygen radicals in LacCer-mediated induction of cell proliferation.
      Superoxide levels were measured by the lucigenin chemiluminescence method, MAPK
      activity was measured by immunocomplex kinase assays, and Western blot analysis
      and c-fos expression were measured by Northern blot assay. We found that LacCer
      (10 microM) stimulates endogenous superoxide production (7-fold compared with
      control) in human aortic smooth muscle cells specifically by activating membrane
      associated NADPH oxidase, but not NADH or xanthine oxidase. This process was
      inhibited by an inhibitor of NADPH oxidase, diphenylene iodonium (DPI), and by
      antioxidants, N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate. NAC and
      DPI both abrogated individual steps in the signaling pathway leading to cell
      proliferation. For example, the p21(ras).GTP loading, p44 MAPK activity, and
      induction of transcription factor c-fos all were inhibited by NAC and DPI as well
      as an antioxidant pyrrolidine dithiocarbamate or reduced glutathione (GSH). In
      contrast, depletion of GSH by L-buthionine (S, R)-sulfoximine up-regulated the
      above described signaling cascade. In sum, LacCer, by virtue of activating NADPH
      oxidase, produces superoxide (a redox stress signaling molecule), which mediates
      cell proliferation via activation of the kinase cascade. Our findings may explain
      the potential role of LacCer in the pathogenesis of atherosclerosis involving the
      proliferation of aortic smooth muscle cells.

PMID- 9188454
TI  - Reactivity of human apurinic/apyrimidinic endonuclease and Escherichia coli
      exonuclease III with bistranded abasic sites in DNA.
AB  - Several oxidative DNA-damaging agents, including ionizing radiation, can generate
      multiply damaged sites in DNA. Among the postulated lesions are those with abasic
      sites located in close proximity on opposite strands. The repair of an abasic
      site requires strand scission by a repair endonuclease such as human
      apurinic/apyrimidinic endonuclease (Ape) or exonuclease III in Escherichia coli.
      Therefore, a potential consequence of the "repair" of bistranded abasic sites is
      the formation of double-strand breaks. To test this possibility and to
      investigate the influence of the relative distance between the two abasic sites
      and their orientation to each other, we prepared a series of oligonucleotide
      duplexes containing abasic sites at defined positions either directly opposite
      each other or separated by 1, 3, or 5 base pairs in the 5'- or 3'-direction.
      Analysis following Ape and exonuclease III treatment of these substrates
      indicated a variety of responses. In general, cleavage at abasic sites was slower
      in duplexes with paired lesions than in control duplexes with single lesions.
      Double-strand breaks were, however, readily generated in duplexes with abasic
      sites positioned 3' to each other. With the duplex containing abasic sites set 1
      base pair apart, 5' to each other, both Ape and exonuclease III slowly cleaved
      the abasic site on one strand only and were unable to incise the other strand.
      With the duplex containing abasic sites set 3 base pairs apart, 5' to each other,
      Ape protein was unable to cleave either strand. These data suggest that closely
      positioned abasic sites could have several deleterious consequences in the cell.
      In addition, this approach has allowed us to map bases that make significant
      contact with the enzymes when acting on an abasic site on the opposite strand.

PMID- 9188455
TI  - Antioxidant activity of vitamin C in iron-overloaded human plasma.
AB  - Vitamin C (ascorbic acid, AA) can act as an antioxidant or a pro-oxidant in
      vitro, depending on the absence or the presence, respectively, of redox-active
      metal ions. Some adults with iron-overload and some premature infants have
      potentially redox-active, bleomycin-detectable iron (BDI) in their plasma. Thus,
      it has been hypothesized that the combination of AA and BDI causes oxidative
      damage in vivo. We found that plasma of preterm infants contains high levels of
      AA and F2-isoprostanes, stable lipid peroxidation end products. However, F2
      isoprostane levels were not different between those infants with BDI (138 +/- 51
      pg/ml, n = 19) and those without (126 +/- 41 pg/ml, n = 10), and the same was
      true for protein carbonyls, a marker of protein oxidation (0.77 +/- 0.31 and 0.68
      +/- 0.13 nmol/mg protein, respectively). Incubation of BDI-containing plasma from
      preterm infants did not result in detectable lipid hydroperoxide formation (</=10
      nM cholesteryl ester hydroperoxides) as long as AA concentrations remained high.
      Furthermore, when excess iron was added to adult plasma, BDI became detectable,
      and endogenous AA was rapidly oxidized. Despite this apparent interaction between
      excess iron and endogenous AA, there was no detectable lipid peroxidation as long
      as AA was present at >10% of its initial concentration. Finally, when iron was
      added to plasma devoid of AA, lipid hydroperoxides were formed immediately,
      whereas endogenous and exogenous AA delayed the onset of iron-induced lipid
      peroxidation in a dose-dependent manner. These findings demonstrate that in iron
      overloaded plasma, AA acts an antioxidant toward lipids. Furthermore, our data do
      not support the hypothesis that the combination of high plasma concentrations of
      AA and BDI, or BDI alone, causes oxidative damage to lipids and proteins in vivo.

PMID- 9188456
TI  - The role of the thioredoxin and glutaredoxin pathways in reducing protein
      disulfide bonds in the Escherichia coli cytoplasm.
AB  - In Escherichia coli, two pathways use NADPH to reduce disulfide bonds that form
      in some cytoplasmic enzymes during catalysis: the thioredoxin system, which
      consists of thioredoxin reductase and thioredoxin, and the glutaredoxin system,
      composed of glutathione reductase, glutathione, and three glutaredoxins. These
      systems may also reduce disulfide bonds which form spontaneously in cytoplasmic
      proteins when E. coli is grown aerobically. We have investigated the role of both
      systems in determining the thiol-disulfide balance in the cytoplasm by
      determining the ability of protein disulfide bonds to form in mutants missing
      components of these systems. We find that both the thioredoxin and glutaredoxin
      systems contribute to reducing disulfide bonds in cytoplasmic proteins. In
      addition, these systems can partially substitute for each other in vivo since
      double mutants missing parts of both systems generally allow substantially more
      disulfide bond formation than mutants missing components of just one system. Some
      of these double mutants were found to require the addition of a disulfide
      reductant to the medium to grow well aerobically. Thus, E. coli requires either a
      functional thioredoxin or glutaredoxin system to reduce disulfide bonds which
      appear after each catalytic cycle in the essential enzyme ribonucleotide
      reductase and perhaps to reduce non-native disulfide bonds in cytoplasmic
      proteins. Our results suggest the existence of a novel thioredoxin in E. coli.

PMID- 9188457
TI  - Identification of three core regions essential for protein splicing of the yeast
      Vma1 protozyme. A random mutagenesis study of the entire Vma1-derived
      endonuclease sequence.
AB  - The translation product of the VMA1 gene of Saccharomyces cerevisiae undergoes
      protein splicing, in which the intervening region is autocatalytically excised
      and the franking regions are ligated. The splicing reaction is catalyzed
      essentially by the in-frame insert, VMA1-derived endonuclease (VDE), which is a
      site-specific endonuclease to mediate gene homing. Previous mutational analysis
      of the splicing reaction has been concentrated extensively upon the splice
      junctions. However, it still remains unknown which amino acid residues are
      crucial for the splicing reaction within the entire region of VDE and its
      neighboring elements. In this work, a polymerase chain reaction-based random
      mutagenesis strategy was used to identify such residues throughout the overall
      intervening sequence of the VMA1 gene. Splicing-defective mutant proteins were
      initially screened using a bacterial expression system and then analyzed further
      in yeast cells. Mutations were mapped at the N- and C-terminal splice junctions
      and around the N-terminal one-third of VDE. We identified four potent mutants
      that yielded aberrant products with molecular masses of 200, 90, and 80 kDa. We
      suggest that the conserved His362, newly identified as the essential residue for
      the splicing reaction, contributes to the first cleavage at the N-terminal
      junction, whereas His736 assists the second cleavage by Asn cyclization at the C
      terminal junction. Mutations in these regions did not appear to destroy the
      endonuclease activity of VDE.

PMID- 9188458
TI  - Selective regulation of agrin mRNA induction and alternative splicing in PC12
      cells by Ras-dependent actions of nerve growth factor.
AB  - The extracellular matrix protein agrin plays an important role in the formation
      and maintenance of the neuromuscular junction. However, regulation of agrin gene
      expression and pre-mRNA splicing, important in determining the biological actions
      of agrin, is not well understood. To begin to identify mechanisms controlling
      agrin expression, quantitative polymerase chain reaction techniques were used to
      analyze the effect of growth factors on the expression of agrin mRNA isoforms in
      rat pheochromocytoma (PC12) cells. Agrin transcripts in untreated cells lacked
      inserts in the Y and Z sites (agriny0z0), encoding agrin isoforms with low
      acetylcholine receptor aggregating activity and a primarily non-neuronal tissue
      distribution. Transcripts encoding isoforms with high aggregating activity and
      neuronal tissue distribution (agriny4z8, agriny4z11, and agriny4z19) were not
      detected. Treatment of PC12 cells with nerve growth factor (NGF) caused a
      significant increase in total agrin mRNA. In contrast, exposure to epidermal
      growth factor had no effect. Analysis of alternative splicing of agrin mRNA
      revealed that NGF elicited a specific increase in agriny4 and agrinz8 mRNAs that
      did not occur in the presence of epidermal growth factor, insulin, dexamethasone,
      or retinoic acid. Analysis of PC12 sublines stably overexpressing a dominant
      inhibitory form of p21 Ras indicated that NGF induced changes in levels of agrin
      mRNA and alternative splicing required Ras activity. The results show that NGF
      can influence important aspects of neuronal differentiation by regulating
      alternative splicing. Furthermore, these data provide insight into the mechanisms
      governing agrin gene expression and suggest that neurotrophic factors may play a
      role in regulating agrin expression in vivo.

PMID- 9188459
TI  - Cloning and characterization of a rhoGAP homolog from Dictyostelium discoideum.
AB  - Small GTPases interact with a variety of proteins that affect nucleotide binding
      and cleavage. GTPase activating proteins (GAPs) are one class of these proteins
      that act by accelerating the intrinsic GTPase rate resulting in the formation of
      the biologically inactive GDP-bound form of the GTPase. For the Rho subfamily of
      GTPases, there is a growing number of proteins with rhoGAP activity that are
      identifiable by a homologous region of about 150 amino acids. We have exploited
      this homology using the polymerase chain reaction to clone the first rhoGAP
      homolog, called DdRacGAP, from the slime mold Dictyostelium discoideum. The GAP
      domain of DdRacGAP (amino acids 1-212), when expressed and purified from
      Escherichia coli, is active on both Dictyostelium and human Rho family GTPases
      but not human Ras. The full-length protein is 1356 amino acids in length and has
      several interesting homologies in addition to the GAP domain, including an SH3
      domain, a dbl homology domain, and a pleckstrin homology domain.

PMID- 9188460
TI  - Ryanodine receptor type III (Ry3R) identification in mouse parotid acini.
      Properties and modulation of [3H]ryanodine-binding sites.
AB  - Immunoblot analysis and [3H]ryanodine binding were used to characterize and
      identify ryanodine receptors (RyRs) in nonexcitable mouse parotid acini. Western
      analysis revealed ryanodine receptor type III (Ry3R) to be the only detectable
      isoform in parotid microsomal membranes. Binding of [3H]ryanodine to microsomal
      fractions was dependent on Ca2+, salt, pH, and temperature. At 23 degrees C, and
      in the presence of 0.5 M KCl and 100 microM Ca2+, [3H]ryanodine bound
      specifically to membranes with high affinity (Kd = 6 nM); maximum binding
      capacity (Bmax) was 275 fmol/mg protein. Mg2+ and ruthenium red inhibited
      [3H]ryanodine binding (IC50 = 1.4 mM and 0.5 microM, respectively). 4-Chloro-3
      ethylphenol enhanced the binding of [3H]ryanodine 2.5-fold; whereas ATP and
      caffeine were much less efficacious toward activating Ry3R (56% and 18% maximal
      enhancement, respectively). Bastadin, a novel modulator of the 12-kDa FK506
      binding protein.RyR complex, increased [3H]ryanodine binding 3-4-fold by
      enhancing Kd. The immunosuppressant FK506 enhanced [3H]ryanodine receptor
      occupancy at >100 microM and antagonized the action of bastadin, suggesting that
      an immunophilin modulates Ry3R in parotid acini. These results suggest that Ry3R
      may play an important role in Ca2+ homeostasis in mouse parotid acini.

PMID- 9188462
TI  - Characterization of thiL, encoding thiamin-monophosphate kinase, in Salmonella
      typhimurium.
AB  - Thiamin pyrophosphate is an essential cofactor that is synthesized de novo by
      Salmonella typhimurium. In bacteria, the end product of the de novo biosynthetic
      pathway is thiamin monophosphate, which is then phosphorylated by thiamin
      monophosphate kinase (EC 2.7.4.16) to form thiamin pyrophosphate. We have
      isolated and characterized the thiL gene of S. typhimurium and showed that thiL
      is a 978-base pair open reading frame encoding a 35-kDa protein with thiamin
      monophosphate kinase activity. thiL was located in the 10-centisome region of the
      S. typhimurium chromosome. We demonstrated that altered thiamin-monophosphate
      kinase activity resulted in decreased repression of transcription of thiamin
      pyrophosphate-regulated thiamin biosynthetic genes. In contrast to other thi
      loci, thiL is not transcriptionally regulated by thiamin pyrophosphate. This
      result is consistent with a dual role for ThiL in de novo biosynthesis and in
      salvage of exogenous thiamin.

PMID- 9188461
TI  - The Escherichia coli SlyD is a metal ion-regulated peptidyl-prolyl cis/trans
      isomerase.
AB  - In Escherichia coli as many as nine different genes coding for proteins with
      significant homology to peptidyl-prolyl cis/trans-isomerases (PPIases) have been
      found. However, for three of them, the histidine-rich SlyD, the homologous gene
      product of ORF149, and parvulin-like SurA, it was not known whether these
      proteins really possess PPIase activity. To gain access to the full set of
      PPIases in E. coli, SlyD, the N-terminal fragment of SlyD devoid of the histidine
      rich region, as well as the protein product of ORF149 of E. coli named SlpA (SlyD
      like protein) were cloned, overexpressed, and purified to apparent homogeneity.
      On the basis of the amino acid sequences, both proteins proved to be of the FK506
      binding protein type of PPIases. Only when using trypsin instead of chymotrypsin
      as helper enzyme in the PPIase assay, the enzymatic activity of full-length SlyD
      and its N-terminal fragment can be measured. For Suc-Ala-Phe-Pro-Arg-4
      nitroanilide as substrate, kcat/Km of 29,600 M-1 s-1 for SlyD and 18,600 M-1 s-1
      for the N-terminal fragment were obtained. Surprisingly, the PPIase activity of
      SlyD is reversibly regulated by binding of three Ni2+ ions to the histidine-rich,
      C-terminal region. Because the PPIase activity of SlpA could be established as
      well, we now know eight distinct PPIases with proven enzyme activity in E. coli.

PMID- 9188463
TI  - Molecular cloning and characterization of human podocalyxin-like protein.
      Orthologous relationship to rabbit PCLP1 and rat podocalyxin.
AB  - Human renal cortex and heart cDNA libraries were screened for a human homolog of
      rabbit PCLP1 using the rabbit PCLP1 cDNA as a probe. Clones spanning 5869 base
      pairs with an open reading frame coding for a 528-amino acid peptide were
      obtained. The putative peptide contains a potential signal peptide and a single
      membrane-spanning region. The extracellular domain contains multiple potential
      sites for N- and O-linked glycosylation and 4 cysteines for potential disulfide
      bonding similar to rabbit PCLP1. On Northern blot a major transcript is seen at
      5.9 kilobases. Antibodies to this protein show a doublet at 160/165 kDa on
      Western blots of human glomerular extract and a pattern of intense glomerular
      staining and vascular endothelial staining on immunofluorescence of human kidney
      sections. Comparison of the rabbit and human peptide sequences shows a high
      degree of identity in the transmembrane and intracellular domains (96%) with a
      lower degree of identity in the extracellular domain (36%). An antibody to the
      intracellular domain reacted across species (human, rabbit, and rat) and
      recognized both rabbit PCLP1 and rat podocalyxin. An interspecies Southern blot
      probed with a cDNA coding for the intracellular domain showed strong
      hybridization to all vertebrates tested in a pattern suggesting a single copy
      gene. We conclude that this cDNA and putative peptide represent the human homolog
      of rabbit PCLP1 and rat podocalyxin.

PMID- 9188464
TI  - A c-erbB-2 promoter-specific nuclear matrix protein from human breast tumor
      tissues mediates NF-kappaB DNA binding activity.
AB  - The c-erbB-2 gene overexpression plays a major role in the pathogenesis of breast
      cancer. Binding studies detected a nuclear matrix protein (NMP) in human breast
      tumor tissues that recognizes a matrix attachment region (MAR) in the immediate
      vicinity of the c-erbB-2 gene promoter. This NMP is expressed in breast tumor
      tissues and cell lines along with c-erbB-2, but is not found in corresponding
      normal tissues. Furthermore, when NMP purified from the breast tumors by its
      affinity to the MAR sequence is added to nuclear extracts of breast cancer cells,
      it selectively stimulates the binding of the NF-kappaB transcription factor to
      DNA. A model is suggested in which the association of the MAR-like sequence with
      the nuclear matrix raises the local concentration of the specific NMP, which in
      turn interacts with the nuclear factor NF-kappaB to increase its local level.
      Such a complex could explain at a molecular level the "increase in NF-kappaB DNA
      binding activity" often observed in c-erbB-2- and BRCA1-positive human breast
      tumors. The increased NF-kappaB activity could thereby contribute to breast
      cancer progression.

PMID- 9188465
TI  - Kinetic analysis of DNA and RNA strand transfer reactions catalyzed by vaccinia
      topoisomerase.
AB  - Vaccinia topoisomerase binds duplex DNA and forms a covalent DNA-(3'
      phosphotyrosyl) protein adduct at the sequence 5'-CCCTT downward arrow. The
      enzyme reacts readily with a 36-mer CCCTT strand (DNA-p-RNA) composed of DNA 5'
      and RNA 3' of the scissile bond. However, a 36-mer composed of RNA 5' and DNA 3'
      of the scissile phosphate (RNA-p-DNA) is a poor substrate for covalent adduct
      formation. Vaccinia topoisomerase efficiently transfers covalently held CCCTT
      containing DNA to 5'-OH-terminated RNA acceptors; the topoisomerase can therefore
      be used to tag the 5' end of RNA in vitro. Religation of the covalently bound
      CCCTT-containing DNA strand to a 5'-OH-terminated DNA acceptor is efficient and
      rapid (krel > 0.5 s-1), provided that the acceptor DNA is capable of base pairing
      to the noncleaved DNA strand of the topoisomerase-DNA donor complex. The rate of
      strand transfer to DNA is not detectably affected by base mismatches at the 5'
      nucleotide of the acceptor strand. Nucleotide deletions and insertions at the 5'
      end of the acceptor slow the rate of religation; the observed hierarchy of
      reaction rates is as follows: +1 insertion > -1 deletion > +2 insertion >> -2
      deletion. These findings underscore the importance of a properly positioned 5'-OH
      terminus in transesterification reaction chemistry, but they also raise the
      possibility that topoisomerase may generate mutations by sealing DNA molecules
      with mispaired or unpaired ends.

PMID- 9188466
TI  - Cyclodextrins are not the major cyclic alpha-1,4-glucans produced by the initial
      action of cyclodextrin glucanotransferase on amylose.
AB  - The initial action of cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) from
      an alkalophilic Bacillus sp. A2-5a on amylose was investigated. Synthetic amylose
      was incubated with purified CGTase then terminated in the very early stage of the
      enzyme reaction. When the reaction mixture was treated with glucoamylase and the
      resulting glucoamylase-resistant glucans were analyzed with high performance
      anion exchange chromatography, cyclic alpha-1,4-glucans, with degree of
      polymerization ranging from 9 to more than 60, in addition to well known alpha-,
      beta-, and gamma-cyclodextrin (CD), were detected. The time-course analysis
      revealed that larger cyclic alpha-1, 4-glucans were preferentially produced in
      the initial stage of the cyclization reaction and were subsequently converted
      into smaller cyclic alpha-1,4-glucans and into the final major product, beta-CD.
      CGTase from Bacillus macerans also produced large cyclic alpha-1, 4-glucans
      except that the final major product was alpha-CD. Based on these results, a new
      model for the action of CGTase on amylose was proposed, which may contradict the
      widely held view of the cyclization reaction of CGTase.

PMID- 9188468
TI  - Localization and suppression of a kinetic defect in cystic fibrosis transmembrane
      conductance regulator folding.
AB  - A growing body of evidence indicates that the most common cystic fibrosis-causing
      mutation, DeltaF508, alters the ability of the cystic fibrosis transmembrane
      conductance regulator (CFTR) protein to fold and transit to the plasma membrane.
      Here we present evidence that the DeltaF508 mutation affects a step on the
      folding pathway prior to formation of the ATP binding site in the nucleotide
      binding domain (NBD). Notably, stabilization of the native state with 4 mM ATP
      does not alter the temperature-dependent folding yield of the mutant DeltaF508
      NBD1 in vitro. In contrast, glycerol, which promotes DeltaF508-CFTR maturation in
      vivo, increases the folding yield of NBD1DeltaF and reduces the off pathway rate
      in vitro, although it does not significantly alter the free energy of stability.
      Likewise a second site mutation, R553M, which corrects the maturation defect in
      vivo, is a superfolder which counters the effects of DeltaF508 on the temperature
      dependent folding yield in vitro, but does not significantly alter the free
      energy of stability. A disease-causing mutation, G551D, which does not alter the
      maturation of CFTR in vivo but rather its function as a chloride channel, and the
      S549R maturation mutation have no discernible effect on the folding of the
      domain. These results demonstrate that DeltaF508 is a kinetic folding mutation
      that affects a step early in the process, and that there is a significant energy
      barrier between the native state and the step affected by the mutation precluding
      the use of native state ligands to promote folding. The implications for protein
      folding in general are that the primary sequence may not necessarily simply
      define the most stable native structure, but rather a stable structure that is
      kinetically accessible.

PMID- 9188467
TI  - Dimerization is essential for DNA binding and repression by the ArsR
      metalloregulatory protein of Escherichia coli.
AB  - Arsenical resistance (ars) operons produce resistance to trivalent and
      pentavalent salts of the metalloids arsenic and antimony in cells of Escherichia
      coli. The first gene in the operon, arsR, was previously shown to encode a
      homodimeric trans-acting metalloregulatory repressor protein. Dimerization of
      ArsR was investigated using the yeast two-hybrid system in which the ArsR protein
      was fused to the Saccharomyces cerevisiae GAL4 DNA-binding domain and GAL4
      activation domain to produce chimeric proteins. Transcriptional activation of
      lacZ reporter indicated that dimerization of the ArsR is stable in yeast. The
      results indicated that residues 1-8 and 90-117 are not required for ArsR
      dimerization. The genes for a series of truncated ArsR proteins containing six
      histidine tags were constructed and the proteins purified. The mass of each
      recombinant protein, as determined by size exclusion chromatography, was
      consistent with the results from two-hybrid analysis. The results of beta
      galactosidase assays in vivo and gel mobility shift assays in vitro showed that
      dimers retained the ability to bind to the ars promoter and to respond to
      inducer, whereas monomeric ArsRs did neither. These results suggest that a core
      sequence of about 80 residues has all of the information necessary for
      dimerization, repression, and metal recognition.

PMID- 9188469
TI  - Cloning, chromosomal mapping, and expression of a novel human secretory
      phospholipase A2.
AB  - Secretory phospholipases A2 (sPLA2s) represent a rapidly expanding family of
      structurally related enzymes found in mammals as well as in insect and snake
      venoms. In this report, a cDNA coding for a novel sPLA2 has been isolated from
      human fetal lung, and its gene has been mapped to chromosome 16p13.1-p12. The
      mature sPLA2 protein has a molecular mass of 13.6 kDa, is acidic (pI 5.3), and
      made up of 123 amino acids. Key structural features of the sPLA2 include: (i) a
      long prepropeptide ending with an arginine doublet, (ii) 16 cysteines located at
      positions that are characteristic of both group I and group II sPLA2s, (iii) a C
      terminal extension typical of group II sPLA2s, (iv) and the absence of elapid and
      pancreatic loops that are characteristic of group I sPLA2s. Based on these
      structural properties, this sPLA2 appears as a first member of a new group of
      sPLA2s, called group X. A 1.5-kilobase transcript coding for the human group X
      (hGX) sPLA2 was found in spleen, thymus, and peripheral blood leukocytes, while a
      less abundant 0.8-kilobase transcript was detected in the pancreas, lung, and
      colon. When the hGX sPLA2 cDNA was expressed in COS cells, sPLA2 activity
      preferentially accumulated in the culture medium, indicating that hGX sPLA2 is an
      actively secreted enzyme. It is maximally active at physiological pH and with 10
      mM Ca2+. hGX sPLA2 prefers phosphatidylethanolamine and phosphatidylcholine
      liposomes to those of phosphatidylserine.

PMID- 9188470
TI  - Endothelial cell heparanase modulation of lipoprotein lipase activity. Evidence
      that heparan sulfate oligosaccharide is an extracellular chaperone.
AB  - A unique feature of lipoprotein lipase (LpL), the rate-limiting enzyme in the
      hydrolysis of circulating triglycerides, is its movement from its cell of
      synthesis, adipocyte or myocyte, to its site of action, the luminal endothelial
      surface. This involves processes that allow LpL to be released from the adipocyte
      cell surface and transferred against the flow of interstitial fluid to the
      luminal surface of endothelial cells. LpL, an unstable enzyme, must retain its
      activity during this process. Whether a chaperone-like molecule is involved in
      LpL stabilization and transport is unclear. In the present study, we tested the
      hypothesis that endothelial cells secrete factors that release LpL and promote
      its transfer to the luminal endothelial surface. Incubation of adipocytes with
      endothelial cell conditioned medium (ECCM) led to release of about 2-fold more
      LpL activity than control medium. Medium from endothelial cells exposed to
      lysophosphatidylcholine (lyso-ECCM), a product of LpL lipolysis of lipoproteins,
      released approximately 3-fold more LpL than ECCM. Concomitant with the release of
      LpL, adipocyte cell surface heparan sulfate (HS) proteoglycans were degraded
      suggesting that lyso-ECCM contained a heparanase-like activity. More heparanase
      was found in media from the basolateral than the apical side of lysolecithin
      stimulated polarized endothelial cells. In coculture experiments, lipolysis and
      lysolecithin stimulation of endothelial cells increased LpL release from
      adipocytes. LpL released by lyso-ECCM remained stable and did not lose enzymatic
      activity at 37 degrees C for 1 h. LpL activity was also stabilized by heparanase
      digested fragments of HS (HS oligosaccharide) and by purified LpL binding
      decasaccharide. Moreover, LpL.HS oligosaccharide complexes crossed endothelial
      cell monolayers and bound to the apical side of the cells. Thus, an endothelial
      heparanase may play a critical role in releasing subendothelial HS bound
      proteins, and specific HS oligosaccharides produced by this enzyme may serve as
      extracellular chaperones.

PMID- 9188471
TI  - Signaling of type II oncostatin M receptor.
AB  - Oncostatin M (OSM) mediates its bioactivities through two different heterodimer
      receptors. They both involve the gp130-transducing receptor, which dimerizes with
      either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to
      generate, respectively, type I and type II OSM receptors. Co-precipitation of
      gp130-associated proteins, flow cytometry, polymerase chain reaction, and
      tyrosine phosphorylation analyses allowed the characterization of both types of
      OSM receptors expressed on the surface of different cell lines. It also allowed
      the detection of a large size protein, p250, that specifically associates to the
      type II OSM receptor components and that is tyrosine-phosphorylated after the
      activation peak of the gp130.OSMRbeta heterocomplex. The restricted expression of
      type I OSM receptor by the JAR choriocarcinoma cell line, and type II receptor by
      the A375 melanoma cell line, permitted the characterization of their signaling
      machineries. Both type I and type II OSM receptors activated Jak1, Jak2, and Tyk2
      receptor-associated tyrosine kinases. The information is next relayed to the
      nucleus by the STAT3 transcriptional activator, which is recruited by both types
      of OSM receptors. In addition, STAT5b was specifically activated through the
      gp130.OSMRbeta type II heterocomplex. The signaling pathway differences observed
      between the common type I LIF/OSM receptor and the specific type II OSM receptor
      might explain some of the bioactivities specifically displayed by OSM.

PMID- 9188472
TI  - Polarized expression of Ca2+ channels in pancreatic and salivary gland cells.
      Correlation with initiation and propagation of [Ca2+]i waves.
AB  - In polarized epithelial cells [Ca2+]i waves are initiated in discrete regions and
      propagate through the cytosol. The structural basis for these compartmentalized
      and coordinated events are not well understood. In the present study we used a
      combination of [Ca2+]i imaging at high temporal resolution, recording of Ca2+
      activated Cl- current, and immunolocalization by confocal microscopy to study the
      correlation between initiation and propagation of [Ca2+]i waves and localization
      of Ca2+ release channels in pancreatic acini and submandibular acinar and duct
      cells. In all cells Ca2+ waves are initiated in the luminal pole and propagate
      through the cell periphery to the basal pole. All three cell types express the
      three known inositol 1,4,5-trisphosphate receptors (IP3Rs). Expression of IP3Rs
      was confined to the area just underneath the luminal and lateral membranes, with
      no detectable receptors in the basal pole or other regions of the cells. In
      pancreatic acini and SMG ducts IP3R3 was also found in the nuclear envelope.
      Expression of ryanodine receptor was detected in submandibular salivary gland
      cells but not pancreatic acini. Accordingly, cyclic ADP ribose was very effective
      in mobilizing Ca2+ from internal stores of submandibular salivary gland but not
      pancreatic acinar cells. Measurement of [Ca2+]i and localization of IP3Rs in the
      same cells suggests that only a small part of IP3Rs participate in the initiation
      of the Ca2+ wave, whereas most receptors in the cell periphery probably
      facilitate the propagation of the Ca2+ wave. The combined results together with
      our previous studies on this subject lead us to conclude that the internal Ca2+
      pool is highly compartmentalized and that compartmentalization is achieved in
      part by polarized expression of Ca2+ channels.

PMID- 9188473
TI  - Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role
      in initiation and propagation of [Ca2+]i waves.
AB  - The present study was aimed at localization of plasma membrane (PMCA) and
      intracellular (SERCA) Ca2+ pumps and characterizing their role in initiation and
      propagation of Ca2+ waves. Specific and polarized expression of Ca2+ pumps was
      observed in all epithelial cells examined. Immunolocalization revealed expression
      of PMCA in both the basolateral and luminal membranes of all cell types. SERCA2a
      appeared to be expressed in the luminal pole, whereas SERCA2b was expressed in
      the basal pole and the nuclear envelope of pancreatic acini. Interestingly,
      SERCA2b was found in the luminal pole of submandibular salivary gland acinar and
      duct cells. These cells expressed SERCA3 in the basal pole. To examine the
      significance of the polarized expression of SERCA and perhaps PMCA pumps in
      secretory cells, we compared the effect of inhibition of SERCA pumps with
      thapsigargine and partial Ca2+ release with ionomycin on Ca2+ release evoked by
      agonists and Ca2+ uptake induced by antagonists. Despite their polarized
      expression, Ca2+ uptake by SERCA pumps and Ca2+ efflux by PMCA resulted in
      uniform reduction in [Ca2+]i. Surprisingly, inhibition of the SERCA pumps, but
      not Ca2+ release by ionomycin, eliminated the distinct initiation sites and
      propagated Ca2+ waves, leading to a uniform increase in [Ca2+]i. In addition,
      inhibition of SERCA pumps reduced the rate of Ca2+ release from internal stores.
      The implication of these findings to rates of Ca2+ diffusion in the cytosol,
      compartmentalization of Ca2+ signaling complexes, and mechanism of Ca2+ wave
      propagation are discussed.

PMID- 9188474
TI  - Disruption of the murine lecithin:cholesterol acyltransferase gene causes
      impairment of adrenal lipid delivery and up-regulation of scavenger receptor
      class B type I.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is the major determinant of the
      cholesteryl ester (CE) content of high density lipoprotein (HDL) in plasma. The
      selective uptake of HDL-CE is postulated to participate in delivery of tissue
      derived cholesterol both to the liver and steroidogenic tissues. Recent studies
      comparing mice with similarly low levels of HDL, due to the absence of either of
      the two major HDL-associated apolipoproteins apoA-I and apoA-II, suggest that
      apoA-I is crucial in modulating this process, possibly through interaction with
      scavenger receptor class B type I (SR-BI). Because of the central role of LCAT in
      determining the size, lipid composition, and plasma concentration of HDL, we have
      created LCAT-deficient mice by gene targeting to examine the effect of LCAT
      deficiency on HDL structure and composition and adrenal cholesterol delivery. The
      HDL in the LCAT-deficient mice was reduced in its plasma concentration (92%) and
      CE content (96%). The HDL particles were heterogeneous in size and morphology and
      included numerous discoidal particles, mimicking those observed in LCAT-deficient
      humans. The adrenals of the male Lcat (-/-) mice were severely depleted of lipid
      stores, which was associated with a 2-fold up-regulation of the adrenal SR-BI
      mRNA. These studies demonstrate that LCAT deficiency, similar to apoA-I
      deficiency, is associated with a marked decrease in adrenal cholesterol delivery
      and supports the hypothesis that adrenal SR-BI expression is regulated by the
      adrenal cholesterol.

PMID- 9188475
TI  - Adhesive bond dynamics in contacts between T lymphocytes and glass-supported
      planar bilayers reconstituted with the immunoglobulin-related adhesion molecule
      CD58.
AB  - The interaction of the T cell glycoprotein CD2 and its ligand CD58 is important
      for T cell interaction with antigen-presenting and target cells. The binding
      interaction is of low affinity and has a fast off-rate (>5 s-1) in solution.
      However, solution measurements may not accurately predict the behavior of
      molecules in an adhesive contact area. Interaction between T cells that express
      CD2 and glass-supported planar bilayers containing purified and fluorescently
      labeled CD58 leads to accumulation of CD58 (fluorescence) in the cell/bilayer
      contact area. CD58 molecules accumulated within the contact area in excess of the
      CD58 density in the bilayer outside the contact area can be considered as bound
      by cell surface CD2. Here, this phenomena and fluorescence photobleaching
      recovery were utilized to determine whether CD2-CD58 bonds are transient in
      contact areas. Fluorescent CD58 molecules accumulated in the T cell-bilayer
      interface were completely bleached. The bleached CD58 molecules accumulated in
      the contact area were rapidly replaced by fluorescent CD58 that diffused into the
      contact area from adjacent bilayer regions outside the contact area. Rapid
      recovery of the accumulated fluorescence directly demonstrates that the CD2-CD58
      bonds are dissociating and that the dissociation leads to partner exchange,
      rather than rebinding of the same CD2-CD58 pairs. This suggests that the solution
      off-rate provides an accurate description of CD2-CD58 interaction in contact
      areas. Accumulated fluorescent IgG in contacts between K562 cells expressing low
      affinity Fc receptors and planar bilayers with fluorescent IgG bound to hapten
      derivitized phospholipids displayed slower recovery than CD58 by a factor of 10.
      This suggests that the Fc receptor-IgG interaction has a longer lifetime than the
      CD2-CD58 interaction. These findings have implications for the mechanism of
      signaling by CD2 and the mechanism of cell detachment from large numbers of
      transient interactions.

PMID- 9188476
TI  - Lipocalin-type prostaglandin D synthase (beta-trace) is a newly recognized type
      of retinoid transporter.
AB  - Lipocalin-type prostaglandin D synthase is responsible for the biosynthesis of
      prostaglandin D2 in the central nervous system and the genital organs and is
      secreted into the cerebrospinal fluid and the seminal plasma as beta-trace. Here
      we analyzed retinoids binding of the enzyme by monitoring the fluorescence
      quenching of an intrinsic tryptophan residue, and appearance of circular
      dichroism around 330 nm, and a red shift of the UV absorption spectra of
      retinoids. We found that the enzyme binds all-trans- or 9-cis-retinoic acid and
      all-trans- or 13-cis-retinal, but not all-trans-retinol, with affinities (Kd of
      70-80 nM) sufficient for function as a retinoid transporter. All-trans-retinoic
      acid inhibited the enzyme activity in a noncompetitive manner, suggesting that it
      binds to the same hydrophobic pocket as prostaglandin H2, the substrate for
      prostaglandin D synthase, but at a different site in this pocket. It is likely
      that this enzyme is a bifunctional protein that acts as both retinoid transporter
      and prostaglandin D2-producing enzyme.

PMID- 9188477
TI  - Inhibition of N-glycan processing in B16 melanoma cells results in inactivation
      of tyrosinase but does not prevent its transport to the melanosome.
AB  - Tyrosinase is the key enzyme in melanin biosynthesis, catalyzing multiple steps
      in this pathway. The mature glycoprotein is transported from the Golgi to the
      melanosome where melanin biosynthesis occurs. In this study, we have investigated
      the effects of inhibitors of N-glycan processing on the synthesis, transport, and
      catalytic activity of tyrosinase. When B16 mouse melanoma cells were cultured in
      the presence of N-butyldeoxynojirimycin, an inhibitor of the endoplasmic
      reticulum-processing enzymes alpha-glucosidases I and II, the enzyme was
      synthesized and transported to the melanosome but almost completely lacked
      catalytic activity. The cells contained only 2% of the melanin found in untreated
      cells. Structural analysis of the N-glycans from N-butyldeoxynojirimycin-treated
      B16 cells demonstrated that three oligosaccharide structures (Glc3Man7-9)
      predominated. Removal of the glucose residues with alpha-glucosidases I and II
      failed to restore enzymatic activity, suggesting that the glucosylated N-glycans
      do not sterically interfere with the enzyme's active sites. The mannosidase
      inhibitor deoxymannojirimycin had no effect on catalytic activity suggesting that
      the retention of glucosylated N-glycans results in the inactivation of this
      enzyme. The retention of glucosylated N-glycans does not therefore result in
      misfolding and degradation of the glycoprotein, as the enzyme is transported to
      the melanosome, but may cause conformational changes in its catalytic domains.

PMID- 9188478
TI  - Toward antibody-directed enzyme prodrug therapy with the T268G mutant of human
      carboxypeptidase A1 and novel in vivo stable prodrugs of methotrexate.
AB  - Antibody-directed enzyme prodrug therapy (ADEPT) has the potential of greatly
      enhancing antitumor selectivity of cancer therapy by synthesizing
      chemotherapeutic agents selectively at tumor sites. This therapy is based upon
      targeting a prodrug-activating enzyme to a tumor by attaching the enzyme to a
      tumor-selective antibody and dosing the enzyme-antibody conjugate systemically.
      After the enzyme-antibody conjugate is localized to the tumor, the prodrug is
      then also dosed systemically, and the previously targeted enzyme converts it to
      the active drug selectively at the tumor. Unfortunately, most enzymes capable of
      this specific, tumor site generation of drugs are foreign to the human body and
      as such are expected to raise an immune response when injected, which will limit
      their repeated administration. We reasoned that with the power of
      crystallography, molecular modeling and site-directed mutagenesis, this problem
      could be addressed through the development of a human enzyme that is capable of
      catalyzing a reaction that is otherwise not carried out in the human body. This
      would then allow use of prodrugs that are otherwise stable in vivo but that are
      substrates for a tumor-targeted mutant human enzyme. We report here the first
      test of this concept using the human enzyme carboxypeptidase A1 (hCPA1) and
      prodrugs of methotrexate (MTX). Based upon a computer model of the human enzyme
      built from the well known crystal structure of bovine carboxypeptidase A, we have
      designed and synthesized novel bulky phenylalanine- and tyrosine-based prodrugs
      of MTX that are metabolically stable in vivo and are not substrates for wild type
      human carboxypeptidases A. Two of these analogs are MTX-alpha-3
      cyclobutylphenylalanine and MTX-alpha-3-cyclopentyltyrosine. Also based upon the
      computer model, we have designed and produced a mutant of human carboxypeptidase
      A1, changed at position 268 from the wild type threonine to a glycine (hCPA1
      T268G). This novel enzyme is capable of using the in vivo stable prodrugs, which
      are not substrates for the wild type hCPA1, as efficiently as the wild type hCPA1
      uses its best substrates (i.e. MTX-alpha-phenylalanine). Thus, the kcat/Km value
      for the wild type hCPA1 with MTX-alpha-phenylalanine is 0.44 microM-1 s-1, and
      kcat/Km values for hCPA1-T268G with MTX-alpha-3-cyclobutylphenylalanine and MTX
      alpha-3-cyclopentyltyrosine are 1.8 and 0.16 microM-1 s-1, respectively. The
      cytotoxic efficiency of hCPA1-268G was tested in an in vitro ADEPT model. For
      this experiment, hCPA1-T268G was chemically conjugated to ING-1, an antibody that
      binds to the tumor antigen Ep-Cam, or to Campath-1H, an antibody that binds to
      the T and B cell antigen CDw52. These conjugates were then incubated with HT-29
      human colon adenocarcinoma cells (which express Ep-Cam but not the Campath 1H
      antigen) followed by incubation of the cells with the in vivo stable prodrugs.
      The results showed that the targeted ING-1:hCPA1-T268G conjugate produced
      excellent activation of the MTX prodrugs to kill HT-29 cells as efficiently as
      MTX itself. By contrast, the enzyme-Campath 1H conjugate was without effect.
      These data strongly support the feasibility of ADEPT using a mutated human enzyme
      with a single amino acid change.

PMID- 9188479
TI  - The nuclear factor kappa-B signaling pathway participates in dysregulation of
      vascular smooth muscle cells in vitro and in human atherosclerosis.
AB  - In the lesions of atherosclerosis, vascular smooth muscle cells (SMC) display
      many functions characteristic of cytokine activation that likely contribute
      importantly to ongoing inflammation during human atherogenesis. The transcription
      factor nuclear factor kappa-B (NFkappaB) often mediates the effects of cytokines
      on target cells, but the identity of Rel family members important in human SMC
      activation remains uncertain. In vitro, human SMC express multiple Rel family
      members. Of these, dimers of p65 and p50, but not a putative SMC-Rel, comprise
      basal and inducible NFkappaB binding activities. SMC express two inhibitor
      proteins IkappaBbeta and IkappaBalpha. Interleukin-1beta stimulation caused
      transient loss of IkappaBalpha and a sustained decrease of IkappaBbeta that
      correlated with increased and persistent levels of p65/p50 protein and binding
      activity in the nucleus. SMC cultured under serum-free conditions displayed
      little NFkappaB activity, but addition of serum or platelet-derived growth factor
      did activate NFkappaB. In situ analyses showed no evidence for basal NFkappaB
      activity in SMC in vivo as nonatherosclerotic arteries did not contain nuclear
      p65 or p50 protein. However, the nuclei of intimal SMC within human atheroma did
      contain both Rel proteins. We conclude that (i) dimers of p65 and p50, but not
      SMC-Rel, comprise NFkappaB complexes in human SMC; (ii) stimulatory components in
      serum activate NFkappaB and likely account for previously reported "constitutive"
      NFkappaB activity in cultured SMC; and (iii) exposure to inflammatory cytokines
      may produce prolonged NFkappaB activation in SMC because of sustained decreases
      in the inhibitory subunit IkappaB-beta.

PMID- 9188480
TI  - cis-4-Methylsphingosine decreases sphingolipid biosynthesis by specifically
      interfering with serine palmitoyltransferase activity in primary cultured
      neurons.
AB  - The effect of six different structurally modified sphingosine analogues on
      biosynthesis of sphingolipids was studied in primary cultured murine cerebellar
      neurons. Treatment of cells with cis-4-methylsphingosine at micromolar levels
      resulted in a markedly decreased sphingolipid biosynthesis, whereas the other
      compounds examined, trans-4-methylsphingosine, cis-5-methylsphingosine, trans-5
      methylsphingosine, cis-sphingosine, and 1-deoxysphingosine, inhibited
      sphingolipid biosynthesis less efficiently. The inhibition of sphingolipid
      biosynthesis by the various compounds was paralleled by a decrease of serine
      palmitoyltransferase activity in situ. For cis-4-methylsphingosine the inhibitory
      effect on serine palmitoyltransferase activity was shown to be concentration- and
      time-dependent. Half-maximal reduction of enzyme activity occurred after 24 h of
      treatment with 10 microM of the compound. The activity of other enzymes of
      sphingolipid biosynthesis as well as phospholipid and protein biosynthesis was
      not affected. Analysis of the sphingoid moiety of cellular sphingolipids suggests
      that the sphingosine analogues listed above were subject to degradation rather
      than being utilized as precursors for sphingolipid biosynthesis by cultured
      neurons. Except of 1-deoxysphingosine, the other five sphingosine analogues were
      shown to be substrates for sphingosine kinase in vitro. After 24 h of treatment
      of primary cerebellar neurons with the various sphingosine analogues the relative
      percentage of the respective intracellular 1-phosphate derivatives paralleled
      exactly the inhibitory effect on serine palmitoyltransferase activity observed
      when cells were treated with the unphosphorylated compounds. In contrast to the
      respective 1-phosphate derivatives of the other methyl-branched sphingosine
      analogues examined, cis-4-methylsphingosine 1-phosphate showed an intracellular
      accumulation suggesting a delayed turnover rate in cultured murine neurons for
      this compound. These results suggest that the inhibitory effect of the
      sphingosine analogues on serine palmitoyltransferase is mediated by their
      respective 1-phosphate derivatives and that the pronounced effect of cis-4
      methylsphingosine is caused by a high intracellular concentration of cis-4
      methylsphingosine 1-phosphate. cis-4-Methylsphingosine, in addition, caused
      drastic changes in cell morphology of primary cerebellar neurons, which were not
      observed when these cells were treated with one of the other sphingosine
      analogues examined.

PMID- 9188481
TI  - Expression cloning of PIG-L, a candidate N-acetylglucosaminyl
      phosphatidylinositol deacetylase.
AB  - Many eukaryotic cell surface proteins are bound to the cell membrane by a
      glycosylphosphatidylinositol (GPI) anchor. Several genes involved in GPI anchor
      biosynthesis have been cloned using complementation of mutant mammalian cell
      lines and yeasts that are defective in its biosynthesis pathway. However, the
      gene involved in the second step of this pathway, in which N-acetylglucosaminyl
      phosphatidylinositol (GlcNAc-PI) is N-deacetylated to form glucosaminyl (GlcN)
      PI, has not been cloned. In this study, we established a GPI anchor-deficient
      mutant of Chinese hamster ovary (CHO) cells defective in the second step.
      Complementation analysis with the known GPI anchor mutant cells demonstrated that
      it belonged to the same complementation group as the CHO cell mutant G9PLAP.85.
      Using the new mutant, we cloned a rat gene termed PIG-L (for phosphatidylinositol
      glycan class L) that is involved in this step. PIG-L encodes a 252-amino acid,
      endoplasmic reticulum membrane protein, most of which is in the cytoplasmic side.
      This orientation of PIG-L protein is consistent with the notion that the second
      step of GPI anchor biosynthesis occurs on the cytoplasmic side of the endoplasmic
      reticulum.

PMID- 9188482
TI  - Differential extraction and protein sequencing reveals major differences in
      patterns of primary cell wall proteins from plants.
AB  - The proteins of the primary cell walls of suspension cultured cells of five plant
      species, Arabidopsis, carrot, French bean, tomato, and tobacco, have been
      compared. The approach that has been adopted is differential extraction followed
      by SDS-polyacrylamide gel electrophoresis (PAGE), rather than two-dimensional gel
      analysis, to facilitate protein sequencing. Whole cells were washed sequentially
      with the following aqueous solutions, CaCl2, CDTA (cyclohexane diaminotetraacetic
      acid, DTT (dithiothreitol), NaCl, and borate. SDS-PAGE analysis showed consistent
      differences between species. From the 233 proteins that were selected for
      sequencing, 63% gave N-terminal data. This analysis shows that (i) patterns of
      proteins revealed by SDS-PAGE are strikingly different for all five species, (ii)
      a large number of these proteins cannot be identified by data base searches
      indicating that a significant proportion of wall proteins have not been
      previously described, (iii) the major proteins that can be identified belong to
      very different classes of proteins, (iv) the majority of proteins found in the
      extracellular growth media are absent from their respective cell wall extracts,
      and (v) the results of the extraction process are indicative of higher order
      structure. It appears that aspects of speciation reside in the complement of
      extracellular wall proteins. The data represent a protein resource for cell wall
      studies complementary to EST (expressed sequence tag) and DNA sequencing
      strategies.

PMID- 9188483
TI  - Dynamic compartmentation of vacuolar amino acids in Penicillium cyclopium.
      Cytosolic adenylates act as a control signal for efflux into the cytosol.
AB  - The regulation of amino acid transport from the vacuolar reservoir into the
      cytoplasm has been studied in hyphal cells of Penicillium cyclopium. To avoid
      artifacts caused by the isolation of vacuoles, efflux was examined "in situ,"
      i.e. in cells whose plasma membranes were permeabilized for micromolecules by a
      treatment with nystatin. The ATP-dependent proton gradient and amino acid
      transport activities at the vacuolar membrane remained intact under these
      conditions. Accumulation of amino acids in the vacuole proved to be the result of
      a dynamic equilibrium of active, ATP-dependent uptake and energy-independent
      efflux. The latter was strongly accelerated after the vacuolar amino acid content
      had surpassed a threshold level. Efflux of vacuolar amino acids was specifically
      controlled by extravacuolar adenylates: ATP, 5'-adenylyl imidodiphosphate (an
      ATPase-resistant ATP-analogue), ADP, or AMP caused a strong inhibition in the
      concentration range around 200 micromol/liter, whereas both lower and higher
      concentrations allowed significant efflux rates. Estimates of the cytosolic
      adenylates (which consisted mainly of ATP) were close to 2 mmol/liter in glucose
      metabolizing cells, which concentration allowed maximum rates of both vacuolar
      uptake and efflux. During 24 h of carbon and nitrogen starvation, the adenylate
      level decreased toward the efflux-inhibiting region around 200 micromol/liter,
      whereas 3-4 d of carbon and nitrogen starvation caused a further decline of the
      adenylate content, leading again to efflux-permitting concentrations. Thus, the
      cytosolic adenylate pool appears to effectively control the availability of
      vacuolar amino acids for the cellular metabolism.

PMID- 9188485
TI  - Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine
      synthase.
AB  - Deoxyhypusine (Nepsilon-(4-aminobutyl)lysine) is the key intermediate in the
      posttranslational synthesis of the unique amino acid, hypusine (Nepsilon-(4-amino
      2-hydroxybutyl)lysine). Deoxyhypusine synthase catalyzes the formation of
      deoxyhypusine by conjugation of the butylamine moiety of spermidine to the
      epsilon-amino group of one specific lysine residue of the eukaryotic translation
      initiation factor 5A (eIF-5A) precursor protein. However, in the absence of the
      eIF-5A precursor, catalysis involves only the NAD-dependent cleavage of
      spermidine to generate 1,3-diaminopropane and a putative 4-carbon amine
      intermediate that gives rise to Delta1-pyrroline. We have obtained evidence for a
      covalent enzyme-substrate intermediate that accumulates in the absence of the eIF
      5A precursor. Incubation of human recombinant enzyme with [1, 8-3H]spermidine and
      NAD, followed by reduction with NaBH3CN, resulted in specific radiolabeling of
      the enzyme. The radioactive component in the reduced enzyme intermediate was
      identified as deoxyhypusine and was shown to occur at a single locus. The fact
      that labeled deoxyhypusine was found after treatment with a reducing agent
      suggests an intermediate with the butylamine moiety derived from spermidine
      attached through an imine linkage to the epsilon-amino group of a specific lysine
      residue of the enzyme. This residue has been identified as lysine 329. Separate
      experiments showing efficient transfer of labeled butylamine moiety from enzyme
      intermediate to eIF-5A precursor strongly support a reaction mechanism involving
      an imine intermediate.

PMID- 9188484
TI  - Residues within the polycationic region of cGMP phosphodiesterase gamma subunit
      crucial for the interaction with transducin alpha subunit. Identification by
      endogenous ADP-ribosylation and site-directed mutagenesis.
AB  - Interaction between the gamma subunit (Pgamma) of cGMP phosphodiesterase and the
      alpha subunit (Talpha) of transducin is a key step for the regulation of cGMP
      phosphodiesterase in retinal rod outer segments. Here we have utilized a
      combination of specific modification by an endogenous enzyme and site-directed
      mutagenesis of the Pgamma polycationic region to identify residues required for
      the interaction with Talpha. Pgamma, free or complexed with the alphabeta subunit
      (Palphabeta) of cGMP phosphodiesterase, was specifically radiolabeled by
      prewashed rod membranes in the presence of [adenylate-32P]NAD. Identification of
      ADP-ribose in the radiolabeled Pgamma and radiolabeling of arginine-replaced
      mutant forms of Pgamma indicate that both arginine 33 and arginine 36 are
      similarly ADP-ribosylated by endogenous ADP-ribosyltransferase, but only one
      arginine is modified at a time. Pgamma complexed with Talpha (both GTP- and GDP
      bound forms) was not ADP-ribosylated; however, agmatine, which cannot interact
      with Talpha, was ADP-ribosylated in the presence of Talpha, suggesting that a
      Pgamma domain containing these arginines is masked by Talpha. A Pgamma mutant
      (R33,36K), as well as wild type Pgamma, inhibited both GTP hydrolysis of Talpha
      and GTP binding to Talpha. Moreover, GTP-bound Talpha activated Palphabeta that
      had been inhibited by R33,36K. However, another Pgamma mutant (R33,36L) could not
      inhibit these Talpha functions. In addition, GTP-bound Talpha could not activate
      Palphabeta inhibited by R33,36L. These results indicate that a Pgamma domain
      containing these arginines is required for its interaction with Talpha, but not
      with Palphabeta, and that positive charges in these arginines are crucial for the
      interaction.

PMID- 9188486
TI  - Functional Co-expression of the canine cardiac Ca2+ pump and phospholamban in
      Spodoptera frugiperda (Sf21) cells reveals new insights on ATPase regulation.
AB  - The utility of the baculovirus cell expression system for investigating Ca2+
      ATPase and phospholamban regulatory interactions was examined. cDNA encoding the
      canine cardiac sarco(endo)plasmic Ca2+-ATPase pump (SERCA2a) was cloned for the
      first time and expressed in the presence and absence of phospholamban in
      Spodoptera frugiperda (Sf21) insect cells. The recombinant Ca2+ pump was produced
      in high yield, contributing 20% of the total membrane protein in Sf21 microsomes.
      At least 70% of the expressed pumps were active. Co-expression of wild-type,
      pentameric phospholamban with the Ca2+-ATPase decreased the apparent affinity of
      the ATPase for Ca2+, but had no effect on the maximum velocity of the enzyme,
      similar to phospholamban's action in cardiac sarcoplasmic reticulum vesicles. To
      investigate the importance of the oligomeric structure of phospholamban in ATPase
      regulation, SERCA2a was co-expressed with a monomeric mutant of phospholamban, in
      which leucine residue 37 was changed to alanine. Surprisingly, monomeric
      phospholamban suppressed SERCA2a Ca2+ affinity more strongly than did wild-type
      phospholamban, demonstrating that the pentamer is not essential for Ca2+ pump
      inhibition and that the monomer is the more active species. To test if
      phospholamban functions as a Ca2+ channel, Sf21 microsomes expressing either
      SERCA2a or SERCA2a plus phospholamban were actively loaded with Ca2+ and then
      assayed for unidirectional 45Ca2+ efflux. No evidence for a Ca2+ channel activity
      of phospholamban was obtained. We conclude that the phospholamban monomer is an
      important regulatory component inhibiting SERCA2a in cardiac sarcoplasmic
      reticulum membranes, and that the channel activity of phospholamban previously
      observed in planar bilayers is not involved in the mechanism of ATPase
      regulation.

PMID- 9188487
TI  - Sequence-specific binding protein of single-stranded and unimolecular quadruplex
      telomeric DNA from rat hepatocytes.
AB  - A rat liver nuclear protein, unimolecular quadruplex telomere-binding protein 25,
      (uqTBP25) is described that binds tightly and specifically single-stranded and
      unimolecular tetraplex forms of the vertebrate telomeric DNA sequence 5'
      d(TTAGGG)n-3'. A near homogeneous uqTBP25 was purified by ammonium sulfate
      precipitation, chromatographic separation from other DNA binding proteins, and
      three steps of column chromatography. SDS-polyacrylamide gel electrophoresis and
      Superdex copyright 200 gel filtration disclosed for uqTBP25 subunit and native Mr
      values of 25.4 +/- 0.5 and 25.0 kDa, respectively. Sequences of uqTBP25 tryptic
      peptides were closely homologous, but not identical, to heterogeneous nuclear
      ribonucleoprotein A1, heterogeneous nuclear ribonucleoprotein A2/B1, and single
      stranded DNA-binding proteins UP1 and HDP-1. Complexes of uqTBP25 with single
      stranded or unimolecular quadruplex 5'-d(TTAGGG)4-3', respectively, had
      dissociation constants, Kd, of 2.2 or 13.4 nM. Relative to d(TTAGGG)4, complexes
      with 5'-r(UUAGGG)4-3', blunt-ended duplex telomeric DNA, or quadruplex telomeric
      DNA had >10 to >250-fold higher Kd values. Single base alterations within the
      d(TTAGGG) repeat increased the Kd of complexes with uqTBP25 by 9-215-fold.
      Association with uqTBP25 protected d(TTAGGG)4 against nuclease digestion,
      suggesting a potential role for the protein in telomeric DNA transactions.

PMID- 9188488
TI  - Heparanase and a synthetic peptide of heparan sulfate-interacting protein
      recognize common sites on cell surface and extracellular matrix heparan sulfate.
AB  - Heparanase is an endo-beta-D-glucuronidase that degrades the glycosaminoglycan
      chains of heparan sulfate (HS) proteoglycans at specific sites. Elevated levels
      of heparanase are associated with the metastatic potential of melanoma and other
      types of tumor cells. We previously reported heparanase degradation of cell
      surface HS subpopulations of the human adenocarcinoma cell line RL95. In the
      present study, heparanase activity was examined on RL95 cell surface HS
      subpopulations in the presence of a synthetic peptide (CRPKAKAKAKAKDQTK) of
      heparin/heparan sulfate-interacting protein (HIP; Liu, S., Smith, S. E., Julian,
      J., Rohde, L. H., Karin, N. J., and Carson, D. D. (1996) J. Biol. Chem. 271,
      11817-11823). Heparanase digestion generated HS fragments from cell surface- or
      extracellular matrix-derived HS of approximately 25 and 9 kDa, respectively. In
      contrast, HS of various size classes isolated from proteoglycans secreted or
      released by RL95 and endothelial cells in culture were not susceptible to
      heparanase digestion. Incubation of heparanase-containing melanoma cellular
      extracts or partially purified heparanase preparations with cell surface- or ECM
      derived HS and HIP peptide, but not a scrambled sequence of this peptide or other
      HS-binding proteins present in ECM, completely inhibited heparanase action.
      Conversely, predigestion of cell surface HS with either heparanase-containing
      cellular extracts or with secreted or partially purified heparanase destroyed
      binding to HIP peptide. Preincubation of HS with HIP peptide prevented subsequent
      heparanase digestion. Collectively, these data demonstrate that HIP peptide and
      heparanase recognize specific, common motifs within HS chains at cell surfaces
      and in ECM and may mutually modulate HS-dependent activities.

PMID- 9188489
TI  - A plasma membrane sucrose-binding protein that mediates sucrose uptake shares
      structural and sequence similarity with seed storage proteins but remains
      functionally distinct.
AB  - Photoaffinity labeling of a soybean cotyledon membrane fraction identified a
      sucrose-binding protein (SBP). Subsequent studies have shown that the SBP is a
      unique plasma membrane protein that mediates the linear uptake of sucrose in the
      presence of up to 30 mM external sucrose when ectopically expressed in yeast.
      Analysis of the SBP-deduced amino acid sequence indicates it lacks sequence
      similarity with other known transport proteins. Data presented here, however,
      indicate that the SBP shares significant sequence and structural homology with
      the vicilin-like seed storage proteins that organize into homotrimers. These
      similarities include a repeated sequence that forms the basis of the reiterated
      domain structure characteristic of the vicilin-like protein family. In addition,
      analytical ultracentrifugation and nonreducing SDS-polyacrylamide gel
      electrophoresis demonstrate that the SBP appears to be organized into oligomeric
      complexes with a Mr indicative of the existence of SBP homotrimers and
      homodimers. The structural similarity shared by the SBP and vicilin-like proteins
      provides a novel framework to explore the mechanistic basis of SBP-mediated
      sucrose uptake. Expression of the maize Glb protein (a vicilin-like protein
      closely related to the SBP) in yeast demonstrates that a closely related vicilin
      like protein is unable to mediate sucrose uptake. Thus, despite sequence and
      structural similarities shared by the SBP and the vicilin-like protein family,
      the SBP is functionally divergent from other members of this group.

PMID- 9188490
TI  - Characterization of Skn-1a/i POU domain factors and linkage to papillomavirus
      gene expression.
AB  - Tissue-restricted POU domain transcription factors, which bind octamer or octamer
      like gene sequences, play roles in cellular differentiation and the development
      of several organs. We have previously identified a POU domain gene, Skn-1a/i,
      expressed primarily in epidermis, that encodes at least two products through
      alternative splicing. One of these, Skn-1a, acts as a transcriptional activator,
      and the other, Skn-1i, contains an inhibitory domain in the NH2 terminus, which
      prevents DNA-binding in vitro and transcriptional activation in vivo. We now
      demonstrate that when Skn-1i is expressed in eukaryotic cells it can bind to an
      octamer site, suggesting that in vivo cellular factors modulate the activity of
      the inhibitory domain to permit DNA-binding. Yet the inhibitory domain does not
      allow transactivation by Skn-1i or by a heterologous transactivator containing
      this domain in cis. Furthermore, we demonstrate that Skn-1a, Tst-1, and Oct-1 are
      the major octamer-binding proteins in epidermis. Since Skn-1a is primarily
      expressed in suprabasal cells of the epidermis, we have tested its possible role
      in the regulation of epidermal papillomaviruses. In transient transfection
      assays, Skn-1a and Tst-1 can activate the long control region of the epidermis
      specific human papillomavirus 1A (HPV-1A). Consistent with these in vivo
      transcription data, in vitro DNA binding studies identify three octamer-like
      sites, which are capable of binding Skn-1a, in the HPV-1A long control region.
      Mutations of all three octamer-like sites prevent transactivation by Skn-1a in
      transient transfection assays. Taken together, these results provide evidence
      that Skn-1a and Tst-1 may provide a molecular link between HPV gene expression
      and epidermal differentiation.

PMID- 9188491
TI  - The RNA polymerase alpha subunit carboxyl-terminal domain is required for both
      basal and activated transcription from the alkA promoter.
AB  - Expression of the Escherichia coli adaptive response genes (ada, aidB, and alkA)
      is regulated by the transcriptional activator, Ada. However, the interactions of
      RNA polymerase and Ada with these promoters differ. In this report we
      characterize the interactions of Ada, methylated Ada (meAda), and RNA polymerase
      at the alkA promoter and contrast these interactions with those characterized
      previously for the ada and aidB promoters. At the alkA promoter, we do not detect
      the RNA polymerase alpha subunit-mediated binary complex detected at the ada and
      aidB promoters. In the presence of either of these two activators, RNA polymerase
      protects the alkA core promoter, including the elements at -35 and -10, and is
      more efficient in transcription initiation in vitro. RNA polymerase holoenzyme
      containing the alpha subunit mutation R265A is severely impaired in Ada
      independent basal alkA transcription, shows no activation by Ada or meAda, and
      fails to bind the alkA promoter in vitro. Binding of the purified wild type alpha
      subunit to alkA was not detected, but a complex of promoter DNA, Ada or meAda,
      and alpha was observed in gel shift assays. These observations suggest that both
      forms of Ada protein activate alkA transcription by enhancing RNA polymerase
      holoenzyme and alpha subunit binding.

PMID- 9188492
TI  - Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated
      protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2
      terminal kinase. Correlation with its inhibitory effect on tumor necrosis factor
      alpha production.
AB  - The enteropathogenic bacterium Yersinia enterocolitica counteracts host defense
      mechanisms by interfering with eukaryotic signal transduction pathways. In this
      study, we investigated the mechanism by which Y. enterocolitica prevents
      macrophage tumor necrosis factor-alpha (TNFalpha) production. Murine J774A.1
      macrophages responded to Y. enterocolitica infection by rapid activation of
      mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase
      (ERK), p38, and c-Jun NH2-terminal kinase (JNK). However, after initial
      activation, the virulent Y. enterocolitica strain harboring the Y. enterocolitica
      virulence plasmid caused a substantial decrease in ERK1/2 and p38 tyrosine
      phosphorylation. Simultaneously, the virulent Y. enterocolitica strain gradually
      suppressed phosphorylation of the transcription factors Elk-1, activating
      transcription factor 2 (ATF2), and c-Jun, indicating time-dependent inhibition of
      ERK1/2, p38, and JNK kinase activities, respectively. Analysis of different Y.
      enterocolitica mutants revealed that (i) MAPK inactivation parallels the
      inhibition of TNFalpha release, (ii) the suppressor effect on TNFalpha
      production, which originates from the lack of TNFalpha mRNA, is distinct from the
      ability of Y. enterocolitica to resist phagocytosis and to prevent the oxidative
      burst, (iii) the tyrosine phosphatase YopH, encoded by the Y. enterocolitica
      virulence plasmid, is not involved in the decrease of ERK1/2 and p38 tyrosine
      phosphorylation or in the cytokine suppressive effect. Altogether, these results
      indicate that Y. enterocolitica possesses one or more virulence proteins that
      suppress TNFalpha production by inhibiting ERK1/2, p38, and JNK kinase
      activities.

PMID- 9188493
TI  - Flanking sequences for the human intercellular adhesion molecule-1 NF-kappaB
      response element are necessary for tumor necrosis factor alpha-induced gene
      expression.
AB  - The regulated expression of intercellular adhesion molecule-1 (ICAM-1) by
      cytokines such as tumor necrosis factor alpha (TNF-alpha) plays an important role
      in inflammation and immune responses. Induction of ICAM-1 gene transcription by
      TNF-alpha has previously been shown to be dependent upon a region of the ICAM-1
      5'-flanking sequences that contains a modified kappaB site. We demonstrate here
      that this modified kappaB site alone is insufficient for induction of
      transcription by TNF-alpha. Site-directed mutagenesis of both the kappaB site and
      specific flanking nucleotides demonstrates that both the specific 5'- and 3'
      flanking sequences and the modified kappaB site are necessary for TNF-alpha
      induction. Further, site-directed mutagenesis of this modified kappaB site to a
      consensus kappaB site allows it to mediate transcriptional activation in response
      to TNF-alpha, even in the absence of specific flanking sequences. Transcription
      through this minimal ICAM-1 TNF-alpha-responsive region can be driven by co
      expression of p65, and the minimal response element interacts with p65 and p50 in
      supershift mobility shift assays. However, when in vitro
      transcription/translation products for the Rel proteins are used in an
      electrophoretic mobility shift assay, only p65 is capable of binding the minimal
      response element while both p50 and p65 bind a consensus kappaB oligonucleotide.
      Additionally, in the absence of the specific flanking nucleotides, the ICAM-1
      kappaB site is incapable of DNA-protein complex formation in both electrophoretic
      mobility shift assay and UV cross-linking/SDS-polyacrylamide gel electrophoresis
      analysis. These results demonstrate the requirement for specific flanking
      sequences surrounding a kappaB binding site for functional transcription factor
      binding and transactivation and TNF-alpha-mediated induction of ICAM-1.

PMID- 9188494
TI  - Promoter structure-dependent functioning of the general transcription factor IIE
      in Saccharomyces cerevisiae.
AB  - General transcription factor (TF) IIE is an essential component of the basal
      transcription complex for protein-encoding genes, which is widely conserved in
      eukaryotes. Here we analyzed requirement for TFIIE for transcription in vivo by
      using yeast Saccharomyces cerevisiae cells harboring mutations in the TFA1 gene
      encoding the larger one of the two subunits of TFIIE. Deletion analysis indicated
      that the N-terminal half of Tfa1 protein has an essential function to support the
      cell growth. In a temperature-sensitive tfa1 mutant cell, the steady-state level
      of bulk poly(A)+ RNA decreased rapidly at the restrictive temperature.
      Surprisingly, levels of several mRNAs, whose transcription is directed by the
      promoters lacking the typical TATA sequence, were not affected in the mutant
      cells at that temperature. This promoter-specific functioning of TFIIE was
      reproduced in a cell-free system composed of TFIIE-depleted nuclear extracts.
      These results strongly suggest that requirement for TFIIE varies in each gene
      depending on the promoter structures in vivo.

PMID- 9188495
TI  - Characterization of a novel tyrosine phosphorylated 100-kDa protein that binds to
      SHP-2 and phosphatidylinositol 3'-kinase in myeloid cells.
AB  - Fms is a tyrosine kinase-containing receptor for macrophage colony-stimulating
      factor (M-CSF) that regulates survival, growth, and differentiation of cells
      along the monocyte/macrophage lineage. M-CSF stimulation of murine myeloid FDC-P1
      cells expressing Fms resulted in the tyrosine phosphorylation of a number of
      signal transduction proteins, including an unidentified 100-kDa protein. This 100
      kDa protein associated with the tyrosine phosphatase SHP-2 but not with the
      related phosphatase SHP-1. The kinetics of tyrosine phosphorylation of p100 and
      SHP-2 suggest that p100 may be a direct substrate of SHP-2. p100 bound directly
      to the SH2 domains of both SHP-2 and the p85 subunit of phosphatidylinositol 3'
      kinase. The 100-kDa protein did not appear to bind directly to Fms, Ship, Cbl,
      Shc, or Grb2, although all of these proteins were coimmunoprecipitated with p85
      after M-CSF stimulation. Association of p100 with SHP-2 and p85 did not require
      the major autophosphorylation sites on Fms nor binding of p85 to Fms. A tyrosine
      phosphorylated protein of 100 kDa also coprecipitated with SHP-2 from several
      other myeloid cell lines after M-CSF stimulation but was not seen in
      immunoprecipitates from Rat2 fibroblasts expressing Fms. Stimulation of FDC-P1
      cells with additional cytokines also resulted in coprecipitation of a 100-kDa
      protein with SHP-2. p100 may therefore be a common component of the signaling
      pathways of cytokine receptors in myeloid cells.

PMID- 9188496
TI  - Copper-specific transcriptional repression of yeast genes encoding critical
      components in the copper transport pathway.
AB  - Copper is an essential micronutrient that is toxic in excess. To maintain an
      adequate yet non-toxic concentration of copper, cells possess several modes of
      control. One involves copper uptake mediated by genes encoding proteins that play
      key roles in high affinity copper transport. These include the FRE1-encoded
      Cu2+/Fe3+ reductase and the CTR1 and CTR3-encoded membrane-associated copper
      transport proteins. Each of these genes is transcriptionally regulated as a
      function of copper availability: repressed when cells are grown in the presence
      of copper and highly activated during copper starvation. Our data demonstrate
      that repression of CTR3 transcription is exquisitely copper-sensitive and
      specific. Although copper represses CTR3 gene expression at picomolar metal
      concentrations, cadmium and mercury down-regulate CTR3 expression only at
      concentrations 3 orders magnitude greater. Furthermore, copper-starvation rapidly
      and potently induces CTR3 gene expression. We demonstrate that the CTR1, CTR3,
      and FRE1 genes involved in high affinity copper uptake share a common promoter
      element, TTTGCTC, which is necessary for both copper repression and copper
      starvation activation of gene expression. Furthermore, the Mac1p is essential for
      down- or up-regulation of the copper-transport genes. In vivo footprinting
      studies reveal that the cis-acting element, termed CuRE (copper-response
      element), is occupied under copper-starvation and accessible to DNA modifying
      agents in response to copper repression, and that this regulated occupancy
      requires a functional MAC1 gene. Therefore, yeast cells coordinately express
      genes involved in high affinity copper transport through the action of a common
      signaling pathway.

PMID- 9188497
TI  - Expression cloning and characterization of oxidative 17beta- and 3alpha
      hydroxysteroid dehydrogenases from rat and human prostate.
AB  - Intracellular levels of active steroid hormones are determined by their relative
      rates of synthesis and breakdown. In the case of the potent androgen
      dihydrotestosterone, synthesis from the precursor testosterone is mediated by
      steroid 5alpha-reductase, whereas breakdown to the inactive androgens 5alpha
      androstane-3alpha, 17beta-diol (3alpha-adiol), and androsterone is mediated by
      reductive 3alpha-hydroxysteroid dehydrogenases (3alpha-HSD) and oxidative 17beta
      hydroxysteroid dehydrogenases (17beta-HSD), respectively. We report the isolation
      by expression cloning of a cDNA encoding a 17beta-HSD6 isozyme that oxidizes
      3alpha-adiol to androsterone. 17beta-HSD6 is a member of the short chain
      dehydrogenase/reductase family and shares 65% sequence identity with retinol
      dehydrogenase 1 (RoDH1), which catalyzes the oxidation of retinol to retinal.
      Expression of rat and human RoDH cDNAs in mammalian cells is associated with the
      oxidative conversion of 3alpha-adiol to dihydrotestosterone. Thus, 17beta-HSD6
      and RoDH play opposing roles in androgen action; 17beta-HSD6 inactivates 3alpha
      adiol by conversion to androsterone and RoDH activates 3alpha-adiol by conversion
      to dihydrotestosterone. The synthesis of an active steroid hormone by back
      conversion of an inactive metabolite represents a potentially important mechanism
      by which the steady state level of a transcriptional effector can be regulated.

PMID- 9188498
TI  - Role of the Arg123-Tyr166 paired helix of apolipoprotein A-I in
      lecithin:cholesterol acyltransferase activation.
AB  - The Arg123-Tyr166 central and Ala190-Gln243 carboxyl-terminal pairs of helices of
      apoA-I were substituted with the pair of helices of apoA-II, resulting in the
      apoA-I(Delta(Arg123-Tyr166), nablaA-II(Ser12-Ala75)) and apoA-I(Delta(Ala190
      Gln243), nablaA-II(Ser12-Gln77)) chimeras, respectively. The structures of these
      chimeras in aqueous solution and in reconstituted high density lipoproteins
      (rHDL) and the lecithin:cholesterol acyltransferase (LCAT) activation properties
      of the rHDL were studied. Recombinant human apoA-I and the chimeras were
      expressed in Escherichia coli and purified from the periplasmic space. Binding of
      the apolipoproteins with palmitoyloleoylphosphatidylcholine was associated with a
      similar shift of Trp fluorescence maxima from 337 to 332 nm, from 339 to 334 nm,
      and from 337 to 333 nm, respectively. All rHDL had a Stokes radius of 4.8 nm and
      contained 2 apolipoprotein molecules/particle. Circular dichroism measurements
      revealed eight alpha-helices per apoA-I and per chimera molecule. The catalytic
      efficiencies of LCAT activation were 1.5 +/- 0.33 (mean +/- S.D.; n = 3), 0.054
      +/- 0.009 (p < 0.001 versus apoA-I), and 1.3 +/- 0.32 (p = not significant versus
      apoA-I) nmol of cholesteryl ester/h/microM, respectively. The lower LCAT activity
      of the central domain chimera was due to a 27-fold reduced Vmax with unaltered
      Km. Binding of radiolabeled LCAT to rHDL of apoA-I and apoA-I(Delta(Arg123
      Tyr166), nablaA-II(Ser12-Ala75)) was very similar. In conclusion, although
      substitution of the Arg123-Tyr166 central or Ala190-Gln243 carboxyl-terminal pair
      of helices of apoA-I with the pair of helices of apoA-II yields chimeras with
      structure similar to that of native apoA-I, exchange of the central domain (but
      not the carboxyl-terminal domain) of apoA-I reduces the rate of LCAT activity
      that is independent of binding to rHDL.

PMID- 9188499
TI  - Interaction of androgen receptors with androgen response element in intact cells.
      Roles of amino- and carboxyl-terminal regions and the ligand.
AB  - Promoter interference assay was employed to examine in intact cells the roles of
      the functional domains of androgen receptor (AR) and the ligand for specific DNA
      interactions using a cytomegalovirus-(androgen response element)-chloramphenicol
      acetyltransferase reporter (pCMV-ARE2-CAT). Native rat and human ARs interfered
      with pCMV-ARE2-CAT expression in a hormone-dependent fashion. Low steroid
      independent interference seemed to occur because of the ligand binding domain
      (LBD), which was transcriptionally inhibitory also in a heterologous context. AR
      devoid of LBD (rARDelta641-902) decreased pCMV-ARE2-CAT activity by 50%. The
      rARDelta46-408 mutant devoid of the NH2-terminal transcription activation region
      exhibited ligand-dependent promoter interference of a similar magnitude. Ligand
      and DNA binding-deficient mutants (hARM807R and rARC562G, respectively) did not
      influence pCMV-ARE2-CAT expression, although hARM807R binds to ARE in vitro. Non
      steroidal anti-androgens casodex and hydroxyflutamide antagonized agonist
      dependent promoter interference, whereas cyproterone acetate, RU 56187, RU 57073,
      and RU 59063 were partial agonists/antagonists. Collectively, interaction of ARs
      with ARE in intact cells does not require the presence of the COOH-terminal or
      NH2-terminal domain and/or their interaction. In the context of native AR,
      however, the androgen-induced conformational change in LBD is mandatory for
      generation of a transcriptionally competent receptor that binds to DNA in intact
      cells.

PMID- 9188500
TI  - Synaptojanin inhibition of phospholipase D activity by hydrolysis of
      phosphatidylinositol 4,5-bisphosphate.
AB  - A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP
      ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) was
      previously purified from rat brain. The sequences of peptides derived from the
      purified PLD inhibitor now identify it as synaptojanin, a nerve terminal protein
      that has been implicated in the endocytosis of fused synaptic vesicles and shown
      to be a member of the inositol polyphosphate 5-phosphatase family. Further
      characterization of the enzymatic properties of synaptojanin now shows that it
      hydrolyzes only the 5-phosphate from inositol 1,4,5-trisphosphate (I(1,4,5)P3)
      and that it does not catalyze the dephosphorylation of either I(1,3,4)P3 or
      inositol 1, 4-bisphosphate. However, synaptojanin hydrolyzes both the 4- and 5
      phosphates of PI(4,5)P2 and the 4-phosphate of phosphatidylinositol 4-phosphate,
      converting both compounds to phosphatidylinositol. Magnesium is required for the
      hydrolysis of I(1,4,5)P3, but not for that of phosphoinositides, by synaptojanin.
      The inhibition of PLD by synaptojanin is attributable to its ability to hydrolyze
      PI(4,5)P2. Synaptojanin did not inhibit PLD in the absence of PI(4,5)P2, and the
      extent of PLD inhibition was related to the extent of PI(4,5)P2 hydrolysis in
      substrate vesicles. It has been proposed that the biosynthesis of PI(4,5)P2 and
      the activation of PLD by ADP-ribosylation factor constitute a positive loop to
      increase rapidly the concentrations of PI(4,5)P2 and phosphatidic acid (PA)
      during membrane vesiculation. The PA thus produced, probably together with
      PI(4,5)P2, facilitates vesicle coat assembly. The hydrolysis of PI(4,5)P2, and
      consequent inhibition of PLD, by synaptojanin might therefore constitute a
      mechanism to halt the positive loop connecting PI(4,5)P2 and PA during the
      endocytotic cycle of synaptic vesicles and serve as a signal for uncoating.

PMID- 9188501
TI  - Inhibition of phospholipase D by clathrin assembly protein 3 (AP3).
AB  - In the accompanying paper (Chung, J.-K., Sekiya, F., Kang, H.-S., Lee, C., Han,
      J.-S., Kim, S. R., Bae, Y. S., Morris, A. J., and Rhee, S. G. (1997) J. Biol.
      Chem. 272, 15980-15985), synaptojanin is identified as a protein that inhibits
      phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and
      phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2). Here, the purification from
      rat brain cytosol of another PLD-inhibitory protein that is immunologically
      distinct from synaptojanin is described, and this protein is identified as
      clathrin assembly protein 3 (AP3) by peptide sequencing and immunoblot analysis.
      AP3 binds both inositol hexakisphosphate and preassembled clathrin cages with
      high affinity. However, neither inositol hexakisphosphate binding nor clathrin
      cage binding affected the ability of AP3 to inhibit PLD. AP3 also binds to
      PI(4,5)P2 with low affinity. But the PI(4,5)P2 binding was not responsible for
      PLD inhibition, because the potency and efficacy of AP3 as an inhibitor of PLD
      were similar in the absence and presence of PI(4,5)P2. A bacterially expressed
      fusion protein, glutathione S-transferase-AP3 (GST-AP3), also inhibited PLD with
      a potency equal to that of brain AP3. The inhibitory effect of AP3 appeared to be
      the result of direct interaction between AP3 and PLD because PLD bound GST-AP3 in
      an in vitro binding assay. Using GST fusion proteins containing various AP3
      sequences, we found that the sequence extending from residues Pro-290 to Lys-320
      of AP3 is critical for both inhibition of and binding to PLD. The fact that AP3
      is a synapse-specific protein indicates that the AP3-dependent inhibition of PLD
      might play a regulatory role that is restricted to the rapid cycling of synaptic
      vesicles.

PMID- 9188502
TI  - Activation transcription factor 1 involvement in the regulation of murine H-2Dd
      expression.
AB  - Resistance to radiation leukemia virus-induced leukemia is correlated with an
      increase in H-2D expression on the thymocyte surface. Recently, it has been shown
      that elevated H-2Dd expression on the infected thymocyte is a result of elevated
      mRNA transcription and that the transcriptional increase is correlated with
      elevated levels of a DNA binding activity, H-2 binding factor 1 (H-2 BF1), which
      recognizes the 5'-flanking sequences (5'-TGACGCG-3') of the H-2Dd gene. This
      target for transcription factor binding has been found to be identical in the 5'
      regulatory region of 12 rodent class I genes, nine of which have been shown to be
      functional genes. Furthermore, this cis-element is found 5' of 20 primate class I
      genes (15 human genes), seven of which are known to be functional. Here, we
      demonstrate that activation transcription factor 1 (ATF-1) is one component of H
      2 BF1. In addition, the levels of ATF-1 mRNA in uninfected and radiation leukemia
      virus-infected thymocytes parallel those of H-2Dd mRNA, and therefore, it is
      suggested that ATF-1 up-regulates the transcription of the H-2Dd gene after
      radiation leukemia virus infection of thymocytes. Transfection experiments also
      demonstrate that ATF-1 activates a reporter plasmid that contains the H-2 BF1
      motif, but not a reporter lacking this motif. This is the first demonstration of
      the interaction of ATF-1 with 5'-regulatory sequences of major histocompatibility
      complex class I genes.

PMID- 9188503
TI  - Identification and characterization of a calmodulin-binding domain in Ral-A, a
      Ras-related GTP-binding protein purified from human erythrocyte membrane.
AB  - A 28-kDa protein (p28) has been purified from Triton X-100 extracts of human
      erythrocyte plasma membrane by calmodulin affinity chromatography. Based on
      internal peptide sequencing and its protein amino acid composition, this protein
      has been shown to be highly related, if not identical to, Ral-A, a Ras-related
      GTP-binding protein. This protein assignment is consistent with the findings that
      p28 binds [32P]GTP specifically and has low GTPase activity. In this study we
      describe the identification and characterization of a calmodulin-binding domain
      in Ral-A. The Ca2+-dependent interaction of p28 with calmodulin was first
      detected by a calmodulin affinity column. Gel overlay experiments of both p28 and
      recombinant Ral-A with biotinylated calmodulin provided strong evidence that Ral
      A is a calmodulin-binding protein. A peptide of 18 residues (P18) with the
      sequence SKEKNGKKKRKSLAKRIR has been identified as a putative calmodulin-binding
      domain in Ral-A, because it comprises a basic/hydrophobic composition with the
      propensity to form an amphiphilic helix. P18 was synthesized, and its interaction
      with calmodulin by gel overlay was shown to be Ca2+-dependent. Circular dichroism
      analysis demonstrated that this interaction results in less alpha-helical content
      upon calmodulin complex formation. These results indicate that Ral-A is a
      calmodulin-binding protein, raising the possibility that it may be associated
      with Ca2+-dependent intracellular signaling pathways.

PMID- 9188504
TI  - A truncated HIV-1 Tat protein basic domain rapidly translocates through the
      plasma membrane and accumulates in the cell nucleus.
AB  - Tat is an 86-amino acid protein involved in the replication of human
      immunodeficiency virus type 1 (HIV-1). Several studies have shown that exogenous
      Tat protein was able to translocate through the plasma membrane and to reach the
      nucleus to transactivate the viral genome. A region of the Tat protein centered
      on a cluster of basic amino acids has been assigned to this translocation
      activity. Recent data have demonstrated that chemical coupling of a Tat-derived
      peptide (extending from residues 37 to 72) to several proteins allowed their
      functional internalization into several cell lines or tissues. A part of this
      same domain can be folded in an alpha-helix structure with amphipathic
      characteristics. Such helical structures have been considered as key determinants
      for the uptake of several enveloped viruses by fusion or endocytosis. In the
      present study, we have delineated the main determinants required for Tat
      translocation within this sequence by synthesizing several peptides covering the
      Tat domain from residues 37 to 60. Unexpectedly, the domain extending from amino
      acid 37 to 47, which corresponds to the alpha-helix structure, is not required
      for cellular uptake and for nuclear translocation. Peptide internalization was
      assessed by direct labeling with fluorescein or by indirect immunofluorescence
      using a monoclonal antibody directed against the Tat basic cluster. Both
      approaches established that all peptides containing the basic domain are taken up
      by cells within less than 5 min at concentrations as low as 100 nM. In contrast,
      a peptide with a full alpha-helix but with a truncated basic amino acid cluster
      is not taken up by cells. The internalization process does not involve an
      endocytic pathway, as no inhibition of the uptake was observed at 4 degrees C.
      Similar observations have been reported for a basic amino acid-rich peptide
      derived from the Antennapedia homeodomain (1). Short peptides allowing efficient
      translocation through the plasma membrane could be useful vectors for the
      intracellular delivery of various non-permeant drugs including antisense
      oligonucleotides and peptides of pharmacological interest.

PMID- 9188505
TI  - Angiotensin II stimulates mitogen-activated protein kinases and protein synthesis
      by a Ras-independent pathway in vascular smooth muscle cells.
AB  - Angiotensin II (ANG II), a potent hypertrophic factor of vascular smooth muscle
      cells (VSMC), induces activation of the ras protooncogene product (Ras) and
      mitogen-activated protein (MAP) kinases and subsequent stimulation of protein
      synthesis in VSMC. In the present study, we examined whether Ras activation is
      required for ANG II-induced MAP kinase activation and stimulation of protein
      synthesis in cultured rat VSMC. Pretreatment with tyrosine kinase inhibitors,
      genistein and herbimycin A, or a putative phosphatidylinositol 3-kinase
      inhibitor, wortmannin, completely blocked ANG II-induced Ras activation, whereas
      neither of them had an effect on ANG II-induced MAP kinase activation. Adenovirus
      mediated expression of a dominant negative mutant of Ha-Ras completely inhibited
      ANG II-induced Ras activation but failed to inhibit MAP kinase activation and
      stimulation of protein synthesis by this vasoconstrictor. These results indicate
      that ANG II stimulates MAP kinases and protein synthesis by a Ras-independent
      pathway in VSMC.

PMID- 9188506
TI  - Role of cyclic ADP-ribose in ATP-activated potassium currents in alveolar
      macrophages.
AB  - There is growing evidence that extracellular ATP causes a dramatic change in the
      membrane conductance of a variety of inflammatory cells. In the present study,
      using the nystatin perforated patch recording configuration, we found that ATP
      (0.3-30 microM) induced a transient outward current in a concentration-dependent
      manner and that the reversal potential of the ATP-induced outward current was
      close to the K+ equilibrium potential, indicating that the membrane behaves like
      a K+ electrode in the presence of ATP. The first application of ATP to alveolar
      macrophages perfused with Ca2+-free external solution could induce the outward
      current, but the response to ATP was diminished with successive applications.
      Intracellular perfusion with a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane
      N,N,N', N'-tetraacetic acid, also diminished the response. When cyclic ADP-ribose
      (cADPR) was applied to the macrophage cytoplasm, a transient outward current was
      elicited. Thereafter, the successive outward current was inhibited, suggesting
      the involvement of cADPR in the response. Intracellular perfusion with inositol
      1,4, 5-trisphosphate also induced a transient outward current, but the successive
      current was not inhibited. The ATP-induced outward current was abolished when 8
      amino-cADPR (as a blocker of cADPR, 10(-6)-10(-5) M) was introduced into the
      cytoplasm. Homogenates of alveolar macrophages showed both ADP-ribosyl cyclase
      and cADPR hydrolase activities, and CD38 (ADP-ribosyl cyclase/cADPR hydrolase)
      expression was confirmed by reverse transcriptase-polymerase chain reaction and
      Western blot analyses. These results indicate that ATP activates K+ currents by
      releasing Ca2+ from cADPR-sensitive internal Ca2+ stores.

PMID- 9188507
TI  - The non-catalytic function of XPG protein during dual incision in human
      nucleotide excision repair.
AB  - XPG is a member of the FEN-1 structure-specific endonuclease family. It has 3'
      junction cutting activity on bubble substrates and makes the 3'-incision in the
      human dual incision (excision nuclease) repair system. To investigate the precise
      role of XPG in nucleotide excision repair, we mutagenized two amino acid residues
      thought to be involved in DNA binding and catalysis, overproduced the mutant
      proteins using a baculovirus/insect cell system, and purified and characterized
      the mutant proteins. The mutation D77A had a modest effect on junction cutting
      and excision activity and gave rise to uncoupled 5'-incision by mammalian cell
      free extracts. The D812A mutation completely abolished the junction cutting and
      3'-incision activities of XPG, but the excision nuclease reconstituted with XPG
      (D812A) carried out normal 5'-incision at the 23rd-24th phosphodiester bonds 5'
      to a (6-4) photoproduct without producing any 3'-incision. It is concluded that
      Asp-812 is an active site residue of XPG and that in addition to making the 3'
      incision, the physical presence of XPG in the protein-DNA complex is required non
      catalytically for subsequent 5'-incision by XPF-ERCC1.

PMID- 9188508
TI  - The cloning of a Caenorhabditis elegans guanylyl cyclase and the construction of
      a ligand-sensitive mammalian/nematode chimeric receptor.
AB  - Substantial guanylyl cyclase activity was detected in membrane fractions prepared
      from Caenorhabditis elegans (100 pmol cGMP/min/mg at 20 degrees C or 500 pmol
      cGMP/min/mg at 37 degrees C), suggesting the potential existence of orphan
      cyclase receptors in the nematode. Using degenerate primers, a cDNA clone
      encoding a putative membrane form of the enzyme (GCY-X1) was obtained. The
      apparent cyclase was most closely related to the mammalian natriuretic peptide
      receptor family, and retained cysteine residues conserved within the
      extracellular domain of the mammalian receptors. Expression of the cDNA in COS-7
      cells resulted in low, but detectable guanylyl cyclase activity (about 2-fold
      above vector alone). The extracellular and protein kinase homology domain of the
      mammalian receptor (GC-B) for C-type natriuretic peptide (CNP) was fused to the
      catalytic domain of GCY-X1 and expressed in COS-7 cells to determine whether
      ligand-dependent regulation would now be obtained. The resulting chimeric protein
      (GC-BX1) was active, and CNP elevated cGMP in a concentration-dependent manner.
      Subsequently, a search of the genome data base demonstrated the existence of at
      least 29 different genes from C. elegans that align closely with the catalytic
      domain of GCY-X1, and thus an equally large number of different regulatory
      ligands may exist.

PMID- 9188509
TI  - Differential regulation of methionine adenosyltransferase in superantigen and
      mitogen stimulated human T lymphocytes.
AB  - Superantigens interact with the T cell receptor for antigen (TCR) and are,
      therefore, more physiological stimulators of T lymphocytes than nonspecific
      polyclonal T cell mitogens. The effects of these two classes of T cell
      stimulators on methionine adenosyltransferase (MAT) and S-adenosylmethionine
      (AdoMet) levels were investigated. Activation of resting human peripheral blood T
      lymphocytes by the mitogen phytohemagglutinin (PHA) or the superantigen
      staphylococcal enterotoxin B (SEB) caused a 3- to 6-fold increase in MAT II
      specific activity. Although the proliferative response was higher in cultures
      stimulated with PHA compared with SEB, MAT II activity was comparable in both
      cultures. Both stimuli caused down-regulation of the MAT 68-kDa lambda subunit
      expression and induced a comparable increase in the expression of the catalytic
      alpha2/alpha2' subunit mRNA and protein. However, in superantigen-stimulated
      cells, the expression of the noncatalytic beta subunit was down-regulated and
      virtually disappeared by 72 h post-stimulation; whereas, no change in the
      expression of this subunit was noted in PHA-stimulated cells. Thus, at 72 h
      following stimulation, PHA-stimulated cells expressed MAT II alpha2/alpha2' and
      beta subunits while SEB-stimulated cells expressed the alpha2/alpha2' subunits
      only; the beta subunit was no longer expressed in superantigen-stimulated cells.
      Kinetic analysis of MAT II in extracts of PHA- and SEB-stimulated cells using
      reciprocal kinetic plots revealed that in the absence of the beta subunit the Km
      of the enzyme for L-methionine (L-Met) was 3-fold higher than in the presence of
      the beta subunit. Furthermore, AdoMet levels were 5-fold higher in cell extracts
      lacking the beta subunit (SEB-stimulated cell extracts) compared with extracts
      containing MAT II alpha2/alpha2' and beta subunits. We propose that the increased
      levels of AdoMet in superantigen-stimulated cells may be attributed to the
      absence of the beta subunit, which seems to have rendered MAT II less sensitive
      to product feedback inhibition by (-)AdoMet. The data suggest that the beta
      subunit of MAT II, which has no catalytic activity, may be a regulatory subunit
      that imparts a lower Km for L-Met but increases the sensitivity to feedback
      inhibition by AdoMet. The down-regulation of the beta subunit, which occurred
      when T cells were stimulated via the TCR, may be an important mechanism to
      regulate AdoMet levels at different stages of T cell differentiation under
      physiological conditions.

PMID- 9188510
TI  - Characterization of a trimeric complex containing Oct-1, SNAPc, and DNA.
AB  - The human small nuclear (sn) RNA promoters contain a proximal sequence element
      (PSE), which recruits the basal transcription factor SNAPc, and a distal sequence
      element characterized by an octamer sequence, which recruits the POU domain
      transcription factor Oct-1. The Oct-1 POU domain and SNAPc bind cooperatively to
      probes containing a PSE and an octamer sequence, and this effect contributes to
      efficient transcription in vitro. In vivo, however, Oct-1 regions outside of the
      POU domain can activate snRNA gene transcription. Here, we have examined whether
      the role of these regions is to contribute to cooperative binding with SNAPc. We
      find that they indeed improve cooperative binding, but most of the effect is
      nevertheless mediated by just the POU domain. This suggests that Oct-1 activates
      transcription of snRNA genes in at least two steps, recruitment of SNAPc mediated
      primarily by the POU domain, and a later step mediated by regions outside of the
      POU domain. We also show that a PSE-binding complex observed in nuclear extracts
      consists of Oct-1 and SNAPc. Although Oct-1 cannot bind effectively to the PSE
      probe on its own, in the complex it contacts DNA. Thus, in a nuclear extract,
      SNAPc can recruit Oct-1 to a probe to which Oct-1 cannot bind on its own.

PMID- 9188512
TI  - Activation of blood coagulation factor X by arginine-specific cysteine
      proteinases (gingipain-Rs) from Porphyromonas gingivalis.
AB  - The effect of two arginine-specific cysteine proteinases (gingipain Rs) from
      Porphyromonas gingivalis, a causative bacterium of adult periodontitis, on human
      blood coagulation was investigated. Activated partial thromboplastin time and
      prothrombin time were shortened by these proteinases, with a 95-kDa gingipain R
      containing adhesin domains being 5-fold more efficient in comparison to a 50-kDa
      gingipain R containing the catalytic domain alone. The 50-kDa enzyme reduced each
      coagulation time in several plasmas deficient in various coagulation factors,
      while it was ineffective in factor X-deficient plasma unless reconstituted with
      this protein. Each proteinase activated factor X in a dose- and time-dependent
      manner, with Michaelis constants (Km) being found to be lower than the normal
      plasma factor X concentration, strongly suggesting that factor X activation by
      gingipain Rs, especially the 95-kDa form which is strongly activated by
      phospholipids, could occur in plasma. This is the first report of factor X
      activation by bacterial proteinases and indicates that the gingipain Rs could be
      responsible for the production of thrombin and, indirectly, with the generation
      of prostaglandins, interleukin-1, etc., which have been found to be associated
      with the development of periodontitis induced by P. gingivalis infections.
      Furthermore, the data support the hypothesis that induction of blood coagulation
      by bacterial proteinases may be a causative agent in the pathogenesis of
      disseminated intravascular coagulation in sepsis.

PMID- 9188511
TI  - Heterotrimeric G-protein Gq/11 localized on pancreatic zymogen granules is
      involved in calcium-regulated amylase secretion.
AB  - The heterotrimeric G-protein Gq/11 was identified on pancreatic acinar zymogen
      granules and its function in calcium-regulated exocytosis was examined. Western
      blotting showed alphaq/11, but not alphas or alphao, to be localized to the
      zymogen granule membrane along with G-protein beta-subunit; all three alpha
      subunits were present in a plasma membrane fraction and the alphaq/11 signal was
      30-fold more enriched in the plasma membrane as compared with granule membrane.
      Neither CCK receptors nor alpha subunits of the sodium pump, both plasma membrane
      markers were present on granule membranes. Immunohistochemistry of pancreatic
      lobules showed that alphaq/11 localized to the zymogen granule-rich apical region
      of acinar cells together with a much stronger signal at the basolateral plasma
      membrane. When the substance-P-related peptide GPAnt-2a, an antagonist of Gq/11,
      was introduced into streptolysin-O permeabilized acini to bypass the plasma
      membrane, the amylase release induced by 10 microM free calcium was potentiated
      in a concentration-dependent manner. By contrast, another substance-P-related
      peptide, GPAnt-1, an antagonist of Go and Gi, showed no effect on calcium-induced
      amylase release from permeabilized acini. GPAnt-2a peptide also exerted an
      inhibitory effect on the total GTPase activity of the purified zymogen granules
      and a larger inhibitory effect on the GTPase activity of the Gq/11 protein
      immunopurified from zymogen granules. GPAnt-1, however, did not inhibit GTPase
      activity of either zymogen granules or immunopurified Gq/11. These results
      suggest that GPAnt-2a peptide augmented calcium-induced amylase release from
      permeabilized acini by inhibiting GTPase activity of the Gq/11 protein on zymogen
      granules. We conclude that Gq/11 protein on zymogen granules plays a tonic
      inhibitory role in calcium-regulated amylase secretion from pancreatic acini.

PMID- 9188513
TI  - The use and abuse of participatory action research.
AB  - This paper outlines the characteristics of PAR, participatory action research, so
      that interested investigators can determine if their project fits the criteria.
      The author introduces some key concepts in critical theory that drive the
      political analysis dimension of PAR and lay to rest concerns about validity and
      legitimacy. Types of PAR are reviewed according to the brand of knowledge focused
      on in the research, and some examples are given. An emerging critique of PAR is
      offered and some abuses of PAR are described. The major ethical principles of
      social justice that guide PAR are outlined. References to epistemology and
      specific methodological demonstration projects are included. Suggestions for
      future use in chronic disease research are offered.

PMID- 9188514
TI  - Using participatory action research to understand the meanings aboriginal
      Canadians attribute to the rising incidence of diabetes.
AB  - This paper discusses the advantages of adopting forms of participatory action
      research with aboriginal Canadians. Using a recent qualitative study of non
      insulin-dependent diabetes mellitus among the James Bay Cree, it outlines and
      discusses the methodology used to construct a form of action research that
      focused on what meaning the Cree gave to the rising incidence and prevalence of
      diabetes. In order to understand this perspective, the researchers recruited
      members of the Cree community as co-researchers in the study. This facilitated
      the development of a Cree perspective on diabetes and also allowed the Cree
      members of the study to acquire a grounding in the knowledge and skills necessary
      for forms of qualitative research that can inform both policy and practice in
      health care and related areas. In particular, the paper discusses how the study
      was constructed and what lessons can be drawn from this form of collaborative
      inquiry.

PMID- 9188515
TI  - The cost of smoking in Canada, 1991.
AB  - In 1991, smoking-attributable health care costs in Canada were $2.5 billion
      (CAN). Additional smoking-attributable costs included $1.5 billion for
      residential care, $2 billion due to workers' absenteeism, $80 million due to
      fires and $10.5 billion due to lost future income caused by premature death.
      Adjustments for future costs if smoking had not occurred and smokers had not died
      were estimated to be $1.5 billion. According to this analysis, smokers cost
      society about $15 billion while contributing roughly $7.8 billion in taxes. The
      results indicate that smoking-attributable costs in Canada have increased
      steadily since 1966 to the 1991 value of $15 billion. Nevertheless, while the
      determination of smoking-attributable costs is important, the issue continues to
      be public health. In addition, for the first time in Canada, the smoking
      attributable cost for residential care has been estimated.

PMID- 9188516
TI  - Utilization of anti-asthma medications in two Quebec populations of anti-asthma
      medication users: a prescription database analysis.
AB  - This study describes the utilization of anti-asthma medications in two groups of
      users of such medications in the province of Quebec, Canada, during the year from
      June 1, 1990, to May 31, 1991. It is based on a secondary analysis of existing
      data banks recording the medications reimbursed by two government-funded
      ambulatory drug reimbursement programs that cover individuals aged 65 and over
      (seniors) and income security (welfare) recipients (ISRs). The study analyzed the
      use of the anti-asthma medications included in the list of medications eligible
      for reimbursement for program beneficiaries. Use was studied in two random
      samples of individuals who had at least one prescription filled for an anti
      asthma medication (2566 seniors and 3695 ISRs). The most commonly used medication
      in both groups was inhaled salbutamol 100 mcg. Various forms of theophylline
      tablets were also used by a high proportion of the sample studied. Over 75% of
      the seniors and 68% of the ISR group used at least one form of theophylline
      during the course of the year. Inhaled corticosteroids were used by 43% of the
      seniors and by 36% of the ISR group, and sympathomimetics (beta 2-agonists), by
      63% of seniors and 68% of ISRs.

PMID- 9188518
TI  - Evaluation of a workshop on Public Education Messages for Reducing Health Risks
      from Ultraviolet Radiation.
AB  - The objective of this paper is to assess the impact of the 1994 Workshop on
      Public Education Messages for Reducing Health Risks from Ultraviolet Radiation
      (UVR). The target audience was any organization in Canada doing education on the
      health risks of UVR. A mailed survey with telephone follow-up was distributed to
      130 addresses, including workshop participants, recipients of the workshop report
      and 40 local public health units. The response rate was 62%. Public health
      messages from the workshop served as an added impetus or helped to initiate
      activities around UVR in approximately 40% of organizations over the two years
      since the workshop. The public health messages were used directly in programming
      by approximately 38% of all organizations responding. However, looking at those
      who had previously seen the messages, 61% used them directly in programming.
      Forty percent of those sampled had never seen a copy of the messages. The results
      suggest the need for improved dissemination of consensus statements.

PMID- 9188517
TI  - Second Symposium on Ultraviolet Radiation-related Diseases.

PMID- 9188525
TI  - Oxygen on Ganymede: laboratory studies.
AB  - To test proposals for the origin of oxygen absorption bands in the visible
      reflectance spectrum of Ganymede, the reflectance of condensed films of pure
      oxygen (O2) and O2-water mixtures and the evolution of O2 from the films as a
      function of temperature were determined. Absorption band shapes and positions for
      oxygen at 26 kelvin were similar to those reported for Ganymede, whereas those
      for the mixtures were slightly shifted. The band intensity dropped by more than
      two orders of magnitude when the ice mixture was warmed to 100 kelvin, although
      about 20 percent of the O2 remained trapped in the ice, which suggested that at
      these temperatures O2 molecules dissolve in the ice rather than aggregate in
      clusters or bubbles. The experiments suggest that the absorption bands in
      Ganymede's spectrum were not produced in the relatively warm surface of the
      satellite but in a much colder source. Solid O2 may exist in a cold subsurface
      layer or in an atmospheric haze.

PMID- 9188526
TI  - Requirement of guanosine triphosphate-bound ran for signal-mediated nuclear
      protein export.
AB  - A leucine-rich nuclear export signal (NES) allows rapid export of proteins from
      cell nuclei. Microinjection studies revealed a role for the guanosine
      triphosphatase (GTPase) Ran in NES-mediated export. Nuclear injection of a Ran
      mutant (Thr24 --> Asn) blocked protein export but not import, whereas depletion
      of the Ran nucleotide exchange factor RCC1 blocked protein import but not export.
      However, injection of Ran GTPase-activating protein (RanGAP) into RCC1-depleted
      cell nuclei inhibited export. Coinjection with Ran mutants insensitive to RanGAP
      prevented this inhibition. Therefore, NES-mediated protein export appears to
      require a Ran-GTP complex but does not require Ran-dependent GTP hydrolysis.

PMID- 9188527
TI  - Inhibition of Ran guanosine triphosphatase-dependent nuclear transport by the
      matrix protein of vesicular stomatitis virus.
AB  - Transport of macromolecules into and out of nuclei, essential steps in gene
      expression, are potential points of control. The matrix protein (M protein) of
      vesicular stomatitis virus (VSV) was shown to block transport of RNAs and
      proteins between the nucleus and cytoplasm of Xenopus laevis oocytes. The pattern
      of inhibition indicated that M protein interfered with transport that is
      dependent on the ras-like nuclear guanosine triphosphatase (GTPase) Ran-TC4 and
      its associated factors. This inhibition of nuclear transport by M protein
      explains several observations about the effects of VSV infection on host cell
      gene expression and suggests that RNA export is closely coupled to protein
      import.

PMID- 9188528
TI  - Transformation of chicken cells by the gene encoding the catalytic subunit of PI
      3-kinase.
AB  - The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas
      in chickens. Analysis of the ASV 16 genome revealed that it encodes an oncogene
      that is derived from the cellular gene for the catalytic subunit of
      phosphoinositide 3-kinase (PI 3-kinase). The gene is referred to as v-p3k, and
      like its cellular counterpart c-p3k, it is a potent transforming gene in cultured
      chicken embryo fibroblasts (CEFs). The products of the viral and cellular p3k
      genes have PI 3-kinase activity. CEFs transformed with either gene showed
      elevated levels of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol
      3,4,5-trisphosphate and activation of Akt kinase.

PMID- 9188529
TI  - Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells
      from multiple myeloma patients.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow
      dendritic cells of multiple myeloma patients but not in malignant plasma cells or
      bone marrow dendritic cells from normal individuals or patients with other
      malignancies. In addition the virus was detected in the bone marrow dendritic
      cells from two out of eight patients with monoclonal gammopathy of undetermined
      significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human
      homolog of which is a growth factor for myeloma, was found to be transcribed in
      the myeloma bone marrow dendritic cells. KSHV may be required for transformation
      from MGUS to myeloma and perpetuate the growth of malignant plasma cells.

PMID- 9188531
TI  - Macrophages as a source of HIV during opportunistic infections.
AB  - The source of increasing viremia that characterizes the latter stages of human
      immunodeficiency virus (HIV) disease has remained a paradox because it occurs at
      a time when lymphoid tissue is quantitatively and qualitatively impaired, and the
      patients' CD4 T lymphocytes are steadily declining. Here, macrophages, both
      infected and uninfected with common opportunistic pathogens of HIV disease such
      as Mycobacterium avium complex and Pneumocystis carinii, were identified as
      highly productive sources of HIV in coinfected lymph nodes. These observations
      indicate that tissue macrophages are not only infected with HIV, but that common
      pathogens of HIV disease can dramatically increase their production of virus.
      Thus, prevention or successful treatment of opportunistic coinfections, or both,
      potentially benefits the patient twofold by limiting the pathology caused by
      opportunistic infection and by controlling induction of HIV replication.

PMID- 9188532
TI  - Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom
      resolution.
AB  - Bactericidal/permeability-increasing protein (BPI), a potent antimicrobial
      protein of 456 residues, binds to and neutralizes lipopolysaccharides from the
      outer membrane of Gram-negative bacteria. At a resolution of 2.4 angstroms, the
      crystal structure of human BPI shows a boomerang-shaped molecule formed by two
      similar domains. Two apolar pockets on the concave surface of the boomerang each
      bind a molecule of phosphatidylcholine, primarily by interacting with their acyl
      chains; this suggests that the pockets may also bind the acyl chains of
      lipopolysaccharide. As a model for the related plasma lipid transfer proteins,
      BPI illuminates a mechanism of lipid transfer for this protein family.

PMID- 9188533
TI  - ARF1, a transcription factor that binds to auxin response elements.
AB  - The plant hormone auxin regulates plant physiology by modulating the interaction
      of transcription factors with auxin response elements (AuxREs) of the affected
      genes. A transcription factor, Auxin Response Factor 1 (ARF1), that binds to the
      sequence TGTCTC in AuxREs was cloned from Arabidopsis by using a yeast one-hybrid
      system. ARF1 has an amino-terminal DNA-binding domain related to the carboxyl
      terminus of the maize transactivator Viviparous-1. Sequence requirements for ARF1
      binding in vitro are identical to those that confer auxin responsiveness in vivo.
      The carboxyl terminus of ARF1 contains two motifs found in the Aux/IAA class of
      proteins and appears to mediate protein-protein interactions.

PMID- 9188534
TI  - Large porous particles for pulmonary drug delivery.
AB  - A new type of inhalation aerosol, characterized by particles of small mass
      density and large size, permitted the highly efficient delivery of inhaled
      therapeutics into the systemic circulation. Particles with mass densities less
      than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers
      were inspired deep into the lungs and escaped the lungs' natural clearance
      mechanisms until the inhaled particles delivered their therapeutic payload.
      Inhalation of large porous insulin particles resulted in elevated systemic levels
      of insulin and suppressed systemic glucose levels for 96 hours, whereas small
      nonporous insulin particles had this effect for only 4 hours. High systemic
      bioavailability of testosterone was also achieved by inhalation delivery of
      porous particles with a mean diameter (20 micrometers) approximately 10 times
      that of conventional inhaled therapeutic particles.

PMID- 9188535
TI  - Specific oxidative cleavage of carotenoids by VP14 of maize.
AB  - The plant growth regulator abscisic acid (ABA) is formed by the oxidative
      cleavage of an epoxy-carotenoid. The synthesis of other apocarotenoids, such as
      vitamin A in animals, may occur by a similar mechanism. In ABA biosynthesis,
      oxidative cleavage is the first committed reaction and is believed to be the key
      regulatory step. A new ABA-deficient mutant of maize has been identified and the
      corresponding gene, Vp14, has been cloned. The recombinant VP14 protein catalyzes
      the cleavage of 9-cis-epoxy-carotenoids to form C25 apo-aldehydes and xanthoxin,
      a precursor of ABA in higher plants.

PMID- 9188536
TI  - Identification of a chemokine receptor encoded by human cytomegalovirus as a
      cofactor for HIV-1 entry.
AB  - The human cytomegalovirus encodes a beta-chemokine receptor (US28) that is
      distantly related to the human chemokine receptors CCR5 and CXCR4, which also
      serve as cofactors for the entry into cells of human immunodeficiency virus-type
      1 (HIV-1). Like CCR5, US28 allowed infection of CD4-positive human cell lines by
      primary isolates of HIV-1 and HIV-2, as well as fusion of these cell lines with
      cells expressing the viral envelope proteins. In addition, US28 mediated
      infection by cell line-adapted HIV-1 for which CXCR4 was an entry cofactor.

PMID- 9188537
TI  - Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha
      subunit.
AB  - Various receptors coupled to the heterotrimeric guanine nucleotide-binding
      protein Gq/11 stimulate formation of inositol-1,4,5-trisphosphate (IP3).
      Activation of these receptors also induces protein tyrosine phosphorylation.
      Formation of IP3 in response to stimulated receptors that couple to Gq/11 was
      blocked by protein tyrosine kinase inhibitors. These inhibitors appeared to act
      before activation of Gq/11. Moreover, stimulation of receptors coupled to Gq/11
      induced phosphorylation on a tyrosine residue (Tyr356) of the Galphaq/11 subunit,
      and this tyrosine phosphorylation event was essential for Gq/11 activation.
      Tyrosine phosphorylation of Galphaq/11 induced changes in its interaction with
      receptors. Therefore, tyrosine phosphorylation of Galphaq/11 appears to regulate
      the activation of Gq/11 protein.

PMID- 9188538
TI  - Overview of functional imaging.
AB  - Provides an overview of the many different modalities of imaging techniques,
      including positron emission tomography, single-photon emission computed
      tomography, functional magnetic resonance imaging, optical imaging, and magnetic
      source imaging.

PMID- 9188539
TI  - Basic principles and neurosurgical applications of positron emission tomography.
AB  - Positron emission tomography (PET) is a technique for studying functional
      processes in the human body in vivo. The important clinical applications of PET
      in neurosurgery include localization of epileptic foci, diagnosis of brain
      tumors, preoperative brain mapping, and the study of plasticity of the brain
      following brain damage. The basic physics and neurosurgical applications of PET
      are presented.

PMID- 9188540
TI  - Imaging studies of memory and attention.
AB  - Functional brain imaging studies of memory and attention with positron emission
      tomography and functional magnetic resonance imaging demonstrate involvement of
      specific regions of the normal human brain. Possible anatomical substrates for
      different types of memory have been identified. Different aspects of attention
      mechanisms, such as modulation of early visual areas, shifts of attention, and
      selection of response, also appear to involve specific anatomic regions revealed
      by imaging. Many of these studies show activation in regions clinically
      considered to be "silent" regions.

PMID- 9188541
TI  - The noninvasive identification of language function. Neuroimaging and rapid
      transcranial magnetic stimulation.
AB  - Neuroimaging techniques that rely on detecting alterations in blood flow may be
      used to map the cortical localization of cognitive function during task
      performance. O-15 water positron emission tomography studies have mapped neural
      networks that subserve language function. These techniques have been adapted to
      lateralize and localize language function in patients with intractable epilepsy
      prior to epilepsy surgery. Functional magnetic resonance (fMR) imaging, relying
      upon fast MR imaging techniques performed during cognitive tasks, allows
      localization of language areas in individual adults and children and, because
      there is no radiation exposure, allows for additional or repeat studies in
      patients. These noninvasive means of language localization may supplant the
      invasive means of language lateralization (intracarotid amytal procedure) and
      localization (corticography), and will allow for the continued study of language
      organization in health and disease.

PMID- 9188542
TI  - Functional brain imaging with cerebral perfusion SPECT in cerebrovascular
      disease, epilepsy, and trauma.
AB  - Functional brain imaging with cerebral perfusion single-photon emission computed
      tomography (SPECT) has practical and important applications for use by
      neurosurgeons in the evaluation of cerebrovascular disease, stroke, epilepsy, and
      trauma. The radiopharmaceuticals used in SPECT enable one to image a "snapshot"
      of regional cerebral blood flow. The findings on SPECT can be the most sensitive
      and unique descriptors of dynamic alterations in brain function due to the
      aforementioned disorders. Used in conjunction with other imaging modalities such
      as magnetic resonance imaging, CT, and neurodiagnostic tests such as EEG and TCD,
      the brain blood flow images enhance the ability of the neurosurgeon to determine
      the perfusion status of the brain.

PMID- 9188543
TI  - Magnetic resonance imaging of human brain function. Principles, practicalities,
      and possibilities.
AB  - This article presents a review of functional magnetic resonance (fMR) imaging.
      Included are four sections that address the principles, practicalities, and
      potentials of fMR imaging. The current types of hemodynamic contrast available
      with fMR imaging, including blood volume, perfusion, and oxygenation, are
      discussed. Technical issues of fMR imaging, including interpretability and
      sensitivity, are described, and several currently unresolved issues are
      addressed. Also reviewed are commonly used fMR imaging platforms and clinical and
      research applications.

PMID- 9188544
TI  - Functional magnetic resonance imaging of the somatosensory cortex.
AB  - Functional magnetic resonance (fMR) imaging, like positron emission tomography
      (PET), shows regions of activation in the brain resulting from the neuronal
      activity associated with cognitive, sensory, or motor function. An advantage of
      fMR imaging is that the functional and the reference anatomic images are acquired
      simultaneously. Additionally, fMR imaging is generally more available than PET or
      magnetoencephalography. This article reviews the applications of fMR imaging for
      studying the sensorimotor cortex prior to craniotomy.

PMID- 9188545
TI  - Functional magnetic resonance imaging. Language mapping.
AB  - This article discusses the use of functional magnetic resonance (fMR) imaging to
      localize language. Suggestions are made for ensuring visualization of language
      areas by selection of effective activation tasks. It is argued that the superior
      temporal gyrus responses evoked by listening to speech represent auditory, rather
      than language, processing. fMR imaging studies using word generation and semantic
      decision tasks are reviewed in detail. These data indicate that fMR imaging is
      capable of mapping language areas in the brain, although results have been
      variable. fMR imaging language results obtained using a semantic decision task
      correspond closely to language laterality measures determined with the Wada test.

PMID- 9188546
TI  - Intrinsic optical changes in neuronal tissue. Basic mechanisms.
AB  - Associated with changes in the level of physiological activity in neuronal tissue
      are changes in the intrinsic optical properties of the tissue. As a consequence,
      it is possible to optically monitor neuronal activity without the use of dyes or
      other contrast-enhancing agents. Such optical techniques have been applied in the
      laboratory for more than 50 years. Recent developments in near-infrared
      spectroscopy and intraoperative optical imaging have suggested a number of
      clinically important applications of this technology. This article provides an
      overview of what is known about the physiological correlates and underlying
      mechanisms associated with activity-evoked optical changes in neuronal tissue.

PMID- 9188547
TI  - Intraoperative optical imaging of epileptiform and functional activity.
AB  - Although intraoperative optical imaging is still a research tool, optical imaging
      has the potential to establish itself as an intraoperative tool in the future,
      and may be able to be used for studies into language dominance, memory, and
      higher cognitive functions.

PMID- 9188548
TI  - Magnetic source imaging as a tool for presurgical functional brain mapping.
AB  - This article describes magnetic source imaging, a newly-developing technology
      which can be used to noninvasively map eloquent cortex prior to surgical
      procedures. It is based on large-array detection of extracranial magnetic fields
      arising from neuronal currents evoked by peripheral stimulation. A range of
      evoked and spontaneous neuromagnetic activities are discussed along with clinical
      examples of the utility of the technique and comparison to other brain mapping
      techniques, such as positron emission tomography, functional magnetic resonance
      imaging, EEG, and ECoG.

PMID- 9188549
TI  - In vivo sequence variability of human immunodeficiency virus type 1 envelope
      gp120: association of V2 extension with slow disease progression.
AB  - According to the rate of depletion of CD4 cell counts, we grouped 12 cases of
      human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8
      cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month)
      progressors and determined the individual viral quasispecies patterns by
      sequencing the genome region encoding the V1, V2, and V3 loops of envelope
      protein. Although the quasispecies structures varied widely from one individual
      to another, a strong correlation was observed between a low rate of disease
      progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2
      loop extension was observed specifically in individuals with slow or no disease
      progression, whereas basic amino acid substitutions in V3 characteristic of a
      viral phenotype shift from non-syncytium inducing to syncytium inducing were
      observed in patients with advanced stages of disease regardless of their rate of
      disease progression. Studies with recombinant viruses suggested that elongation
      of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages.
      Thus, our results suggest the association of distinct sequence features of both
      V3 and V2 with particular patterns of disease progression. Elongation of the V2
      loop may be a good predictor of slow disease progression, while basic
      substitutions of V3 without elongation of V2 are characteristic of rapid
      progression.

PMID- 9188550
TI  - Identification of the site of Epstein-Barr virus persistence in vivo as a resting
      B cell.
AB  - Epstein-Barr (EBV) is a powerful immortalizing virus for human B lymphocytes in
      vitro and is associated with several human neoplasias in vivo. Previously, we
      have shown that the majority of EBV-infected cells in the peripheral blood of
      healthy, persistently infected individuals do not express the activated
      phenotype, e.g., high levels of cell surface CD23 and CD80 (B7),
      characteristically expressed on in vitro-immortalized cells. Here, we show that >
      or = 90% of the CD23-, virus-infected cells in the peripheral blood are in G0 and
      therefore resting. The remaining cells may be G1 arrested, but we were unable to
      detect a significant number of cells traversing the S-G2-M stages of the cell
      cycle. The mRNA for LMP2A, but not EBNA1 originating from Qp, was readily
      detected in this population, and these cells appear competent in the processing
      and presentation of antigen by class I major histocompatibility complex. We
      propose that these resting B cells are the site of long-term latent persistence
      for EBV. We further propose that the persistence of the virus in a resting B7- B
      cell provides an important mechanism to escape immunosurveillance. The
      demonstration that EBV can persist latently in a resting B cell means that the
      immortalizing functions of EBV can be down regulated in a normal B cell. This
      conclusion has important implications for understanding and controlling EBV
      associated neoplasia.

PMID- 9188551
TI  - Inactivation of the human immunodeficiency virus type 1 inhibitory elements
      allows Rev-independent expression of Gag and Gag/protease and particle formation.
AB  - The expression of gag, pol, and env of human immunodeficiency virus type 1 (HIV
      1) depends on the presence of the viral Rev protein. This dependence is, at least
      in part, due to the presence of negatively acting sequences (inhibitory or
      instability elements [INS]) located within unspliced and partially spliced mRNAs.
      The positive interaction of Rev with the Rev-responsive element in these mRNAs
      counteracts the negative effects of the inhibitory sequences. Here, we
      demonstrate that in addition to the previously identified INS1 within p17gag,
      several other INS elements exist within the gag/pol region of HIV-1. These
      elements act independently of each other and were eliminated by mutagenesis after
      the introduction of multiple point mutations not affecting the coding region,
      leading to constitutive high levels of Gag expression. Expression vectors
      containing an intact or nearly intact p55gag region allowed the production of
      immature viral particles in mammalian cells in the absence of any other HIV
      proteins. The introduction of additional mutations in the protease region allowed
      efficient production of Gag/protease, which resulted in processing of the Pr55gag
      precursor and production of mature Gag particles with a lentivirus-like conical
      core structure. The elimination of a newly identified INS element within pol and
      the previously identified CRS located within int was accomplished by the same
      methodology. Sequence comparisons of the identified inhibitory elements revealed
      no apparent homologies and demonstrated that these sequences are not splice
      sites. These results demonstrate that the elimination of INS elements leads to
      efficient expression of HIV-1 mRNAs in the absence of Rev or any
      posttranscriptional activating mechanisms.

PMID- 9188553
TI  - Expression of the poliovirus receptor in intestinal epithelial cells is not
      sufficient to permit poliovirus replication in the mouse gut.
AB  - Although the initial site of poliovirus replication in humans is the intestine,
      previously isolated transgenic mice which carry the human poliovirus receptor
      (PVR) gene (TgPVR mice), which develop poliomyelitis after intracerebral
      inoculation, are not susceptible to infection by the oral route. The low levels
      of PVR expressed in the TgPVR mouse intestine might explain the absence of
      poliovirus replication at that site. To ascertain whether PVR is the sole
      determinant of poliovirus susceptibility of the mouse intestine, we have
      generated transgenic mice by using the promoter for rat intestine fatty acid
      binding protein to direct PVR expression in mouse gut. Pvr was detected by
      immunohistochemistry in the enterocytes and M cells of transgenic mouse (TgFABP
      PVR) small intestine. Upon oral inoculation with poliovirus, no increase in virus
      titer was detected in the feces of TgFABP-PVR mice, and no virus replication was
      observed in the small intestine, although poliovirus replicated in the brain
      after intracerebral inoculation. The failure of poliovirus to replicate in the
      TgFABP-PVR mouse small intestine was not due to lack of virus binding sites,
      because poliovirus could attach to fragments of small intestine from these mice.
      These results indicate that the inability of poliovirus to replicate in the mouse
      alimentary tract is not solely due to the absence of virus receptor, and other
      factors are involved in determining the ability of poliovirus to replicate in the
      mouse gut.

PMID- 9188552
TI  - The ICP0 protein of equine herpesvirus 1 is an early protein that independently
      transactivates expression of all classes of viral promoters.
AB  - To assess the role of the equine herpesvirus type 1 (EHV-1) ICP0 protein (EICP0)
      in gene regulation, a variety of molecular studies on the EICP0 gene and gene
      products of both the attenuated cell culture-adapted Kentucky A (KyA) strain and
      the Ab4p strain were conducted. These investigations revealed that (i) the ICP0
      open reading frame (ORF) of the KyA virus strain is 1,257 bp in size and would
      encode a protein of 419 amino acids, and in comparison to the ICP0 gene (ORF63)
      of the Ab4p strain of 1,596 bp (E. A. Telford, M. S. Watson, K. McBride, and A.
      J. Davison, Virology 189:304-316, 1992), it has an internal in-frame deletion of
      339 bp; (ii) one early transcript of 1.4 kb predicted to encode the EICP0 protein
      and a late transcript of 1.8 kb are detected in Northern blot analyses using
      probes containing the EICP0 ORF; (iii) the KyA EICP0 protein (50 kDa) and the
      Ab4p EICP0 protein (80 kDa) are expressed as several species of early proteins
      that are first detected at 3 to 4 h postinfection by Western blot analyses of
      infected-cell polypeptides, using an antiserum generated to a TrpE fusion protein
      that harbors amino acids 46 to 153 of the EICP0 protein; and (iv) the EICP0
      protein of both EHV-1 strains is a potent transactivator of EHV-1 genes.
      Transient expression assays using a simian virus 40 expression construct of the
      EICP0 protein of the KyA strain showed that the EICP0 protein independently
      transactivated chloramphenicol acetyltransferase reporter constructs under the
      control of the immediate-early promoter (3.9-fold), the early thymidine kinase
      promoter (95-fold), the late (gamma1) IR5 promoter (85-fold), and the late
      (gamma2) glycoprotein K promoter (21-fold). The finding that the EICP0 protein of
      the KyA virus can function as an activator of gene expression indicates that
      amino acids corresponding to residues 319 to 431 of the Ab4p EICP0 protein are
      not essential for EICP0 transactivation of EHV-1 promoters.

PMID- 9188554
TI  - Mutations in reovirus outer-capsid protein sigma3 selected during persistent
      infections of L cells confer resistance to protease inhibitor E64.
AB  - Mutations selected in reoviruses isolated from persistently infected cultures (PI
      viruses) affect viral entry into cells. Unlike wild-type (wt) viruses, PI viruses
      can grow in the presence of ammonium chloride, a weak base that blocks acid
      dependent proteolysis of viral outer-capsid proteins in cellular endosomes during
      viral entry. In this study, we show that E64, an inhibitor of cysteine proteases
      such as those present in the endocytic compartment, blocks growth of wt reovirus
      by inhibiting viral disassembly. To determine whether PI viruses can grow in the
      presence of an inhibitor of endocytic proteases, we compared yields of wt and PI
      viruses in cells treated with E64. Prototype PI viruses L/C, PI 2A1, and PI 3-1
      produced substantially greater yields than wt viruses type 1 Lang (T1L) and type
      3 Dearing (T3D) in E64-treated cells. To identify viral genes that segregate with
      growth of PI viruses in the presence of E64, we tested reassortant viruses
      isolated from independent crosses of T1L and each of the prototype PI viruses for
      growth in cells treated with E64. Growth of reassortant viruses in the presence
      of E64 segregated exclusively with the S4 gene, which encodes viral outer-capsid
      protein sigma3. These results suggest that mutations in sigma3 protein selected
      during persistent infection alter its susceptibility to cleavage during viral
      disassembly. To determine the temporal relationship of acid-dependent and
      protease-dependent steps in reovirus disassembly, cells were infected with wt
      strain T1L or T3D, and medium containing either ammonium chloride or E64d, a
      membrane-permeable form of E64, was added at various times after adsorption.
      Susceptibility to inhibition by both ammonium chloride and E64 was abolished when
      either inhibitor was added at times greater than 60 min after adsorption. These
      findings indicate that acid-dependent and protease-dependent disassembly events
      occur with similar kinetics early in reovirus replication, which suggests that
      these events take place within the same compartment of the endocytic pathway.

PMID- 9188556
TI  - Genomic diversity and evolution of papillomaviruses in rhesus monkeys.
AB  - We are studying the diversity of and relationships among papillomaviruses (PVs)
      to understand the modes and timescales of PV evolution and in the hope of finding
      animal PVs that may serve as model systems for disease caused by human PVs
      (HPVs). Toward this goal, we have examined 326 genital samples from rhesus
      monkeys and long-tailed macaques with a PCR protocol optimized for detecting
      genital HPV types. In 28 of the rhesus monkey samples, we found amplicons derived
      from 12 different and novel PV genomes, RhPV-a to RhPV-m, with the likely
      taxonomic status of "type." The frequency with which novel RhPVs were detected
      suggests that rhesus monkeys may play host to PVs with a diversity similar to
      that of humans. In phylogenetic trees, all 12 of the different RhPVs and the
      previously described type RhPV-1 were members of the genital HPV supergroup and
      formed three minor branches distinct from the 11 branches formed by genital HPVs.
      We also identified a novel PV amplicon, MfPV-a, from a long-tailed macaque, a
      species belonging to the same genus as rhesus monkeys. MfPV-a turned out to be a
      close relative of five RhPVs. It appears that the evolution of primate lineages
      leading to the genus Macaca and to humans created transmission barriers for PVs,
      resulting in viral evolution closely linked to the host. Additional support for
      the linked-evolution hypothesis comes from considering the phylogenetic
      association of two other ape and monkey PVs with the genital HPVs, the supergroup
      formed by at least seven ungulate PVs, and the isolated phylogenetic position of
      the only known bird PV.

PMID- 9188557
TI  - Analysis of the gene start and gene end signals of human respiratory syncytial
      virus: quasi-templated initiation at position 1 of the encoded mRNA.
AB  - The gene start (GS) and gene end (GE) transcription signals of human respiratory
      syncytial virus (RSV) strain A2 were analyzed in helper-dependent monocistronic
      and dicistronic minireplicons which were complemented by a standard RSV strain.
      The GS signal, which is the start site for mRNA synthesis, is highly conserved
      for the first nine genes: 3'-CCCCGUUUA(U/C) (negative sense). This conserved
      version of the signal was analyzed by "saturation" mutagenesis, in which all 10
      positions, as well as one downstream and one upstream position, were changed one
      at a time into each of the other three nucleotides. Most of the positions appear
      to contribute to the signal: positions 1, 3, 6, 7, and, in particular, 9 were the
      most sensitive, whereas position 5 was relatively insensitive. The effect of
      nucleotide substitution in the first position of the signal was examined further
      by cDNA cloning and sequence analysis of the residual mRNA which was produced.
      For the two mutants examined (1C to U, and 1C to A), the site of initiation was
      unchanged. However, the mRNAs were dimorphic with regard to the assignment of the
      5'-terminal nucleotide: two-thirds contained the predicted mutant substitution,
      and one-third contained the parental assignment. Intracellular minigenome
      contained only the mutant assignment, indicating that the heterogeneity was at
      the level of transcription by the RSV polymerase. This suggests that the
      templated mutant assignment at position 1 can sometimes be overridden by an
      innate preference for the parental assignment, a phenomenon which we dubbed quasi
      templated initiation. The GS signal of the L gene, encoding the 10th RSV mRNA,
      contains three differences (3'-CCCUGUUUUA) compared to the conserved version. It
      was shown to be equal in efficiency to the conserved version. This was
      unexpected, since the saturation mutagenesis described above indicated that U in
      place of A at position 9 should be highly inhibitory. Instead, the A at position
      10 of the L GS signal was found to be critical for activity, indicating that an
      essential A residue indeed was present in both versions of the GS signal but that
      its spacing differed. The GE signal, which directs termination and
      polyadenylation, has more sequence diversity in nature than does the GS signal.
      The naturally occurring GE signals of strain A2 were compared by their individual
      incorporation into a dicistronic minigenome. They were similar in the ability to
      produce translatable mRNA except in the cases of NS1 and NS2, which were
      approximately 60% as efficient.

PMID- 9188555
TI  - Localized sequence heterogeneity in the long terminal repeats of in vivo isolates
      of equine infectious anemia virus.
AB  - The role of in vivo long terminal repeat (LTR) sequence variation of the
      lentivirus equine infectious anemia virus (EIAV) has not been explored. In this
      study, we investigated the heterogeneity found in the LTR sequences from seven
      EIAV-seropositive horses: three horses with clinical disease and four horses
      without any detectable signs of disease. LTR sequences were targeted in this
      study because the LTR U3 enhancer region of tissue culture-derived isolates has
      been identified as one of the few hypervariable regions of the EIAV genome.
      Furthermore, LTR variation may regulate EIAV expression in vivo. Both intra- and
      interanimal sequence variations were investigated. The intra-animal variation was
      low in seropositive, healthy horses (on average 0.44%). Intra-animal variation
      was consistently higher in clinically ill horses (0.99%), suggesting that greater
      numbers of quasispecies of EIAV are present when active virus replication is
      ongoing. Interanimal comparisons of consensus sequences generated from each horse
      demonstrated that the enhancer region is a hotspot of sequence variation in vivo.
      Thirty-seven of the 83 nucleotides that compose the U3 enhancer region were
      variable between the different in vivo-derived LTRs. The remainder of the LTR
      that was analyzed was more conserved, 8 of 195 nucleotide positions being
      variable. Results of electrophoretic mobility shift assays demonstrated that some
      nucleotide substitutions that occurred in the enhancer region eliminated or
      altered transcription factor binding motifs that are known to be important for
      EIAV LTR expression. These data suggested that the selective pressures exerted on
      the EIAV LTR enhancer sequences are different from those exerted on the remainder
      of the LTR. Our findings are consistent with the possibility that enhancer
      sequence hypervariability can alter expression of the virus in tissue macrophages
      and therefore contribute to clinical disease in infected horses.

PMID- 9188559
TI  - Biochemical characterizations of two temperature-sensitive and attenuated strains
      of respiratory syncytial virus subgroup B.
AB  - Cold-adapted, temperature-sensitive (ts), attenuated strains of respiratory
      syncytial virus have been developed from a B subgroup clinical isolate for
      potential use as vaccine candidates. The replication of two B subgroup ts mutant
      viruses (2B33F and 2B20L) at the permissive and nonpermissive temperatures have
      been compared with that of the parental 2B virus to establish differences that
      may account for their ts and/or attenuated phenotypes. We have shown that the ts
      restriction at 39 degrees C in the replication of the two mutant viruses in
      tissue culture occurs at a step after virus adsorption but before or including
      initiation of virus-specific mRNA transcription. At the permissive temperature of
      32 degrees C a 12- to 24-h delay in the accumulation of mRNA for both mutant
      viruses in comparison to that of the parental 2B virus was exhibited. This effect
      was mirrored by equivalent delays in viral protein synthesis and production of
      infectious virus. By 36 h postinfection both mutants had produced levels of viral
      mRNA, protein, and infectious virus that were similar to those of the parent
      virus at 32 degrees C. ts+ revertant viruses derived from both mutants have also
      reverted in their viral mRNA, protein, and infectious virus production kinetics
      at 32 degrees C to rates more like those exhibited by the parental 2B virus. This
      suggests a positive correlation between the ts step in the replication of the
      mutant viruses and the initial delay in mRNA production that occurs at the
      permissive temperature.

PMID- 9188560
TI  - Sequence- and structure-specific determinants in the interaction between the RNA
      encapsidation signal and reverse transcriptase of avian hepatitis B viruses.
AB  - Hepatitis B viruses (HBVs) replicate by reverse transcription of an RNA
      intermediate. Packaging of this RNA pregenome into nucleocapsids and replication
      initiation depend crucially on the interaction of the reverse transcriptase, P
      protein, with the cis-acting, 5' end-proximal encapsidation signal epsilon. The
      overall secondary structure is similar in all of the hepadnaviral epsilon
      signals, with a lower and an upper stem, separated by a bulge, and an apical
      loop. However, while epsilon is almost perfectly conserved in all mammalian
      viruses, the epsilon signals of duck HBV (DHBV) and heron HBV (D epsilon and H
      epsilon, respectively) differ substantially in their upper stem regions, both in
      primary sequence and in secondary structure; nonetheless, H epsilon interacts
      productively with DHBV P protein, as shown by its ability to stimulate priming,
      i.e., the covalent attachment of a deoxynucleoside monophosphate to the protein.
      In this study, we extensively mutated the variable and the conserved positions in
      the upper stem of D epsilon and correlated the functional activities of the
      variant RNAs in a priming assay with secondary structure and physical P protein
      binding. These data revealed a proper overall structure, with the bulge and
      certain key residues, e.g., in the loop, being important constraints in protein
      binding. Many mutations at the evolutionarily variable positions complied with
      these criteria and yielded priming-competent RNAs. However, most mutants at the
      conserved positions outside the loop were defective in priming even though they
      had epsilon-like structures and bound to P protein; conversely, one point mutant
      in the loop with an apical structure different from those of D epsilon and H
      epsilon was priming competent. These results suggest that P protein binding can
      induce differently structured epsilon RNAs to adopt a new, common conformation,
      and they support an induced-fit model of the epsilon-P interaction in which both
      components undergo extensive structural alterations during formation of a priming
      competent ribonucleoprotein complex.

PMID- 9188558
TI  - Nuclear localization of the NS3 protein of hepatitis C virus and factors
      affecting the localization.
AB  - Subcellular localization of the NS2 and NS3 proteins of hepatitis C virus was
      analyzed. In stable Ltk transfectants inducibly expressing an NS2-NS3 polyprotein
      (amino acids [aa] 810 to 1463), processed full-size NS2 (aa 810 to 1026) was
      detected exclusively in a cytoplasmic membrane fraction. On the other hand, the
      other processed product, carboxy-truncated NS3 (NS3 deltaC1463; aa 1027 to 1463),
      was present in both cytoplasmic and nuclear fractions. To further analyze
      subcellular localization of NS3, NS3 deltaC1459 (aa 1027 to 1459), full-size NS3
      (NS3F; aa 1027 to 1657), and both amino- and carboxy-truncated NS3 (NS3
      deltaNdeltaC; aa 1201 to 1459) were expressed in HeLa cells by using a vaccinia
      virus-T7 hybrid expression system. NS3 deltaC1459 and NS3F accumulated in the
      nucleus as well as in the cytoplasm, exhibiting a dot-like staining pattern. On
      the other hand, NS3 deltaNdeltaC was localized predominantly in the cytoplasm,
      suggesting the presence of a nuclear localization signal(s) in the amino-terminal
      sequence of NS3. NS4A, a viral cofactor for the NS3 protease, inhibited nuclear
      transport of NS3 deltaC1459 and NS3F, with the latter inhibited to a lesser
      extent than was the former. Interestingly, wild-type p53 tumor suppressor
      augmented nuclear localization of NS3 deltaC1459 and NS3F, whereas mutant-type
      p53 inhibited nuclear localization and augmented cytoplasmic localization of NS3
      deltaC1459. However, subcellular localization of NS3 deltaNdeltaC was not
      affected by either type of p53. Wild-type p53-mediated nuclear accumulation of
      NS3 deltaC1459 and NS3F was inhibited partially, but not completely, by
      coexpressed NS4A, with NS3F again affected less prominently than was NS3
      deltaC1459.

PMID- 9188561
TI  - Protection of human immunodeficiency virus type 2-exposed seronegative macaques
      from mucosal simian immunodeficiency virus transmission.
AB  - At present it is not known which form of immunity would be most effective against
      infection with human immunodeficiency virus (HIV). To evaluate the possible role
      of cellular immunity, we examined whether four HIV type 2-exposed but
      seronegative macaques developed cellular immune responses and determined whether
      these exposed macaques were resistant to mucosal transmission of simian
      immunodeficiency virus (SIV). Following intrarectal challenge with SIV, 2 monkeys
      were protected against detectable SIV replication and another showed suppressed
      viral replication compared to 14 persistently infected controls. The two
      protected monkeys demonstrated SIV-specific cytotoxic T lymphocytes before as
      well as after SIV challenge. Here we provide evidence that activation of the cell
      mediated arm of the immune system only, without antibody formation, can control
      SIV replication in macaques. The results imply that vaccines that stimulate a
      strong and broad cellular immune response could prevent mucosal HIV transmission.

PMID- 9188562
TI  - GB virus B and hepatitis C virus NS3 serine proteases share substrate
      specificity.
AB  - GB virus B (GBV-B) is a recently discovered virus responsible for hepatitis in
      tamarins (Saguinus species). GBV-B belongs to the Flaviviridae family and is
      closely related to the human pathogen hepatitis C virus (HCV). Nonstructural
      protein 3 (NS3) of HCV has been shown to encompass a serine protease domain
      required for viral maturation. GBV-B and HCV share only about 30% of the amino
      acid sequence within the NS3 protease domain. The catalytic triad is conserved,
      and the residue Phe-154, presumed to be a crucial amino acid for determining the
      S1 specificity pocket of the HCV NS3 protease, is also conserved. We have
      expressed a synthetic gene encoding the GBV-B NS3 protease domain in Escherichia
      coli and have characterized the purified recombinant protein for its activity on
      HCV substrates. We have shown that the NS3 region of the GBV-B genome actually
      encodes a serine protease that, despite the low sequence homology, shares
      substrate specificity with the HCV NS3 protease.

PMID- 9188563
TI  - Two parvoviruses that cause different diseases in mink have different
      transcription patterns: transcription analysis of mink enteritis virus and
      Aleutian mink disease parvovirus in the same cell line.
AB  - The two parvoviruses of mink cause very different diseases. Mink enteritis virus
      (MEV) is associated with rapid, high-level viral replication and acute disease.
      In contrast, infection with Aleutian mink disease parvovirus (ADV) is associated
      with persistent, low-level viral replication and chronic severe immune
      dysregulation. In the present report, we have compared viral transcription in
      synchronized CRFK cells infected with either MEV or ADV using a nonradioactive
      RNase protection assay. The overall level of viral transcription was 20-fold
      higher in MEV- than in ADV-infected cells. Furthermore, MEV mRNA encoding
      structural proteins (MEV mRNA R3) was dominant throughout the infectious cycle,
      comprising approximately 80% of the total viral transcription products. In marked
      contrast, in ADV-infected cells, transcripts encoding nonstructural proteins (ADV
      mRNA R1 and R2) comprised more than 84% of the total transcripts at all times
      after infection, whereas ADV mRNA R3 comprised less than 16%. Thus, the ADV mRNA
      coding for structural proteins (ADV mRNA R3) was present at a level at least 100
      fold lower than the corresponding MEV mRNA R3. These findings paralleled previous
      biochemical studies analyzing in vitro activities of the ADV and MEV promoters
      (J. Christensen, T. Storgaard, B. Viuff, B. Aasted, and S. Alexandersen, J.
      Virol. 67:1877-1886, 1993). The overall low levels of ADV mRNA and the paucity of
      the mRNA coding for ADV structural proteins may reflect an adaptation of the
      virus for low-level restricted infection.

PMID- 9188564
TI  - Construction of a vaccinia virus deficient in the essential DNA repair enzyme
      uracil DNA glycosylase by a complementing cell line.
AB  - The vaccinia virus D4R open reading frame, encoding the essential DNA repair
      enzyme uracil DNA glycosylase, was expressed in two permanent cell lines, the
      rabbit kidney cell line RK13 and the human fibroblast cell line 293. The
      temperature-sensitive vaccinia virus mutant ts4149, which maps within D4R, was
      able to grow under restrictive conditions in both of these transformed cell
      lines. Cell clones complemented D4R function to various degrees, demonstrating
      complementation of an essential vaccinia virus gene by a cell line constitutively
      expressing the essential function. Thus, the complementing host cells allowed the
      rescue of a virus defective in the D4R gene, demonstrating that this system may
      be used for the propagation of defective cytoplasmic DNA viruses. The defective
      virus grew to high yields only in the engineered cell lines. The data support the
      hypothesis that early gene products, such as uracil DNA glycosylase, supplied in
      trans can fully complement essential viral functions.

PMID- 9188565
TI  - Multiple extracellular domains of CCR-5 contribute to human immunodeficiency
      virus type 1 entry and fusion.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry is governed by the interaction
      of the viral envelope glycoprotein (Env) with its receptor. The HIV-1 receptor is
      composed of two molecules, the CD4 binding receptor and a coreceptor. The seven
      membrane-spanning chemokine receptor CCR-5 is one of the coreceptors used by
      primary isolates of HIV-1. We demonstrate that the mouse homolog of CCR-5 (mCCR
      5) does not function as an HIV-1 coreceptor. A set of chimeras of human CCR-5 and
      mCCR-5 was studied for Env-induced cell fusion and HIV-1 infection. Using the HIV
      1ADA envelope glycoprotein in a syncytium formation assay, we show that
      replacement of any fragment containing extracellular domains of mCCR-5 by its
      human counterparts is sufficient to allow Env-induced fusion. Conversely,
      replacement of any fragment containing human extracellular domains by its murine
      counterpart did not lead to coreceptor function loss. These results show that
      several domains of CCR-5 participate in coreceptor function. In addition, using a
      panel of primary nonsyncytium-inducing and syncytium-inducing isolates that use
      CCR-5 or both CXCR-4 and CCR-5 as coreceptors, we show that the latter dual
      tropic isolates are less tolerant to changes in CCR-5 than strains with a more
      restricted coreceptor use. Thus, different strains are likely to have different
      ways of interacting with the CCR-5 coreceptor.

PMID- 9188566
TI  - Herpes simplex virus type 1 glycoprotein K is not essential for infectious virus
      production in actively replicating cells but is required for efficient
      envelopment and translocation of infectious virions from the cytoplasm to the
      extracellular space.
AB  - We characterized the glycoprotein K (gK)-null herpes simplex virus type 1 [HSV-1]
      (KOS) delta gK and compared it to the gK-null virus HSV-1 F-gKbeta (L. Hutchinson
      et al., J. Virol. 69:5401-5413, 1995). delta gK and F-gKbeta mutant viruses
      produced small plaques on Vero cell monolayers at 48 h postinfection. F-gKbeta
      caused extensive fusion of 143TK cells that was sensitive to melittin, a specific
      inhibitor of gK-induced cell fusion, while delta gK virus did not fuse 143TK
      cells. A recombinant plasmid containing the truncated gK gene specified by F
      gKbeta failed to rescue the ICP27-null virus KOS (d27-1), while a plasmid with
      the delta gK deletion rescued the d27-1 virus efficiently. delta gK virus yield
      was approximately 100,000-fold lower in stationary cells than in actively
      replicating Vero cells. The plaquing efficiencies of delta gK and F-gKbeta virus
      stocks on VK302 cells were similar, while the plaquing efficiency of F-gKbeta
      virus stocks on Vero cells was reduced nearly 10,000-fold in comparison to that
      of delta gK virus. Mutant delta gK and F-gKbeta infectious virions accumulated
      within Vero and HEp-2 cells but failed to translocate to extracellular spaces.
      delta gK capsids accumulated in the nuclei of Vero but not HEp-2 cells. Enveloped
      delta gK virions were visualized in the cytoplasms of both Vero and HEp-2 cells,
      and viral capsids were found in the cytoplasm of HEp-2 cells within vesicles.
      Glycoproteins B, C, D, and H were expressed on the surface of delta gK-infected
      Vero cells in amounts similar to those for KOS-infected Vero cells. These results
      indicate that gK is involved in nucleocapsid envelopment, and more importantly in
      the translocation of infectious virions from the cytoplasm to the extracellular
      spaces, and that actively replicating cells can partially compensate for the
      envelopment but not for the cellular egress deficiency of the delta gK virus.
      Comparison of delta gK and F-gKbeta viruses suggests that the inefficient viral
      replication and plaquing efficiency of F-gKbeta virus in Vero cells and its
      syncytial phenotype in 143TK- cells are most likely due to expression of a
      truncated gK.

PMID- 9188567
TI  - The shiverer mutation affects the persistence of Theiler's virus in the central
      nervous system.
AB  - Theiler's virus persists in the white matter of the spinal cord of genetically
      susceptible mice and causes primary demyelination. The virus persists in
      macrophages/microglial cells, but also in oligodendrocytes, the myelin-forming
      cells. Susceptibility/resistance to this chronic infection has been mapped to
      several loci including one tentatively located in the telomeric region of
      chromosome 18, close to the myelin basic protein locus (Mbp locus). To determine
      if the MBP gene influences viral persistence, we inoculated C3H mice bearing the
      shiverer mutation, a 20-kb deletion in the gene. Whereas control C3H mice were of
      intermediate susceptibility, C3H mice heterozygous for the mutation were very
      susceptible, and those homozygous for the mutation were completely resistant.
      This resistance was not immune mediated. Furthermore, C3H/101H mice homozygous
      for a point mutation in the gene coding for the proteolipid protein of myelin,
      the rumpshaker mutation, were resistant. These results strongly support the view
      that oligodendrocytes are a necessary viral target for the establishment of a
      persistent infection by Theiler's virus.

PMID- 9188568
TI  - In vivo dynamics of equine infectious anemia viruses emerging during febrile
      episodes: insertions/duplications at the principal neutralizing domain.
AB  - Equine infectious anemia virus (EIAV) is a good model for studying mechanisms
      generating escaped retrovirus variants. We previously sequenced the entire gp90
      encoding region of 22 cDNA clones obtained from five antigenically distinct
      isolates (F1V to F5V) recovered during febrile episodes in horse 493
      experimentally infected with the Japanese virulent EIAV strain V70. The results
      showed that the mutations occurred in the principal neutralizing domain (PND) by
      insertions/duplications. In this study, we further characterized the PND of virus
      isolates sequentially recovered during 22 febrile episodes in seven horses newly
      infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA
      clones derived from the 22 episodes confirmed the generation of various new viral
      quasispecies with insertions/duplications in the PND. Although the
      insertion/duplication sequences in a total of 92 cDNA clones were extensively
      heterogeneous, we hypothesized that all the insertions/duplications occurred
      during reverse transcription from viral genomic RNA to minus strand DNA. The
      insertion/duplication regions were derived from a part of the PND sequence, which
      consisted of five small units. These small units, some with various substitutions
      and/or deletions, were also generated, especially in regions with
      insertions/duplications. Of particular note was that all these virus variants,
      except for two cDNA variants, were generated by essentially four different
      duplication pathways. Thus, these results extend the significance of
      insertions/duplications in the PND to the novel generation of EIAV in vivo during
      febrile episodes.

PMID- 9188569
TI  - Identification and characterization of a baculovirus structural protein, VP1054,
      required for nucleocapsid formation.
AB  - The defect in a temperature-sensitive mutant of Autographa californica nuclear
      polyhedrosis virus, tsN1054, was mapped and characterized. At the nonpermissive
      temperature of 33 degrees C, this mutant fails to form plaques upon infection of
      Sf-21 cultured insect cells; infection is limited to a single cell, even though
      the infection proceeds through the very late phase. Marker rescue mapping and DNA
      sequencing identified the gene, ORF 54, which was altered by a single nucleotide
      substitution in tsN1054. Transcriptional analysis of the ORF 54 region identified
      multicistronic RNAs, from early to very late times of infection, that potentially
      encode the ORF 54 gene product. Polyclonal antiserum raised to a TrpE-VP1054
      fusion protein recognized a 42-kDa late protein, VP1054, in infected-cell
      lysates. VP1054 was found to be a component of both budded virus and occlusion
      derived virions. The level of VP1054 was dramatically reduced in tsN1054-infected
      Sf-21 cells propagated at 33 degrees C, and electron microscopic analysis of
      these cells showed that nucleocapsids failed to form in the nuclei of these
      infected cells. Instead, novel round, electron-dense bodies were found associated
      with the virogenic stroma in tsN1054-infected cells. Therefore, VP1054 is a virus
      structural protein required for nucleocapsid assembly.

PMID- 9188570
TI  - The human cytomegalovirus UL55 (gB) and UL75 (gH) glycoprotein ligands initiate
      the rapid activation of Sp1 and NF-kappaB during infection.
AB  - The cellular transcription factors Sp1 and NF-kappaB were upregulated shortly
      after the binding of purified live or UV-inactivated human cytomegalovirus (HCMV)
      to the cell surface. The rapid time frame of transcription factor induction is
      similar to that seen in other systems in which cellular factors are induced
      following receptor-ligand engagement. This similarity suggested that a cellular
      receptor-viral ligand interaction might be involved in Sp1 and NF-kappaB
      activation during the earliest stages of HCMV infection. To focus on the possible
      role viral ligands play in initiating cellular events following infection, we
      first used purified viral membrane extracts to demonstrate that constituents on
      the membrane are responsible for cellular activation. Additionally, these studies
      showed, through the use of neutralizing antibodies, that the viral membrane
      mediators of this activation are the major envelope glycoproteins gB (UL55) and
      gH (UL75). To confirm these results, neutralizing anti-gB and -gH antibodies were
      used to block the interactions of these glycoproteins on whole purified virus
      with their cell surface receptors. In so doing, we found that Sp1 and NF-kappaB
      induction was inhibited. Lastly, through the use of purified viral gB protein and
      an anti-idiotypic antibody that mimics the image of the viral gH protein, it was
      found that the engagement of individual viral ligands with their appropriate cell
      surface receptors was sufficient to activate cellular Sp1 and NF-kappaB. These
      results support our hypothesis that HCMV glycoproteins mediate an initial signal
      transduction pathway which leads to the upregulation of host cell transcription
      factors and suggests a model wherein the orderly sequence of virus-mediated
      changes in cellular activation initiates with viral binding via envelope
      glycoproteins to the cognate cellular receptor(s).

PMID- 9188571
TI  - Specific targeting to CD4+ cells of recombinant vesicular stomatitis viruses
      encoding human immunodeficiency virus envelope proteins.
AB  - We generated replication-competent, recombinant vesicular stomatitis viruses
      (VSVs) expressing the human immunodeficiency virus (HIV) envelope protein or an
      HIV-VSV chimeric envelope protein in which the cytoplasmic domain of the HIV
      envelope protein was replaced with that from the VSV glycoprotein (G). These
      recombinants were generated with HIV type 1 (HIV-1) envelopes from both
      laboratory and primary isolates of HIV-1. The replication-competent recombinant
      viruses were stable and expressed the foreign proteins at high levels from extra
      transcription units in VSV. The foreign proteins were processed appropriately and
      transported to the cell surface. The incorporation of HIV gp120 into VSV
      particles was demonstrated biochemically only for the construct expressing the
      chimeric envelopes containing the VSV G cytoplasmic domain. The incorporation of
      the chimeric HIV envelope protein into the membrane of the recombinant VSV was
      also demonstrated by electron microscopy with gold-conjugated antibodies. To
      determine whether specific infection of CD4-positive cells could be demonstrated
      for these recombinants, we neutralized VSV infectivity due to VSV glycoprotein
      with anti-VSV serum. The neutralized recombinants expressing the chimeric
      envelope were able to infect only HeLa cells expressing CD4, and this CD4
      specific infectivity was neutralized with anti-HIV serum. This assay also
      detected a 100-fold-lower titer of CD4-specific infectivity for the VSV
      recombinant expressing the wild-type HIV envelope. Our results illustrate that it
      is possible to express functional HIV envelopes from the VSV genome and target
      the recombinant virus to an alternative receptor. The recombinants may also prove
      useful as HIV vaccines.

PMID- 9188572
TI  - Evolution of envelope-specific antibody responses in monkeys experimentally
      infected or immunized with simian immunodeficiency virus and its association with
      the development of protective immunity.
AB  - Previous studies of attenuated simian immunodeficiency virus (SIV) vaccines in
      rhesus macaques have demonstrated the development of broad protection against
      experimental challenge, indicating the potential for the production of highly
      effective immune responses to SIV antigens. However, the development of this
      protective immune status was found to be critically dependent on the length of
      time postvaccination with the attenuated virus strain, suggesting a necessary
      maturation of immune responses. In this study, the evolution of SIV envelope
      specific antibodies in monkeys experimentally infected with various attenuated
      strains of SIV was characterized by using a comprehensive panel of serological
      assays to assess the progression of antibodies in longitudinal serum samples that
      indicate the development of protective immunity. In parallel studies, we also
      used the same panel of antibody assays to characterize the properties of SIV
      envelope-specific antibodies elicited by inactivated whole-virus and envelope
      subunit vaccines previously reported to be ineffective in producing protective
      immunity. The results of these studies demonstrate that the evolution of
      protective immunity in monkeys inoculated with attenuated strains of SIV is
      associated with a complex and lengthy maturation of antibody responses over the
      first 6 to 8 months postinoculation, as reflected in progressive changes in
      antibody conformational dependence and avidity properties. The establishment of
      long-term protective immunity at this time in general parallels the absence of
      further detectable changes in antibody responses and a maintenance of relatively
      constant antibody titer, avidity, conformational dependence, and the presence of
      neutralizing antibody for at least 2 years postinoculation. In contrast to the
      mature antibody responses elicited by the attenuated SIV vaccines, the whole
      virus and envelope subunit vaccines in general elicited only immature antibody
      responses characterized by poor reactivity with native envelope proteins, low
      avidity, low conformational dependence, and the absence of neutralization
      activity against the challenge strain. Thus, these studies establish for the
      first time an association between the effectiveness of experimental vaccines and
      the capacity of the vaccine to produce a mature antibody response to SIV envelope
      proteins and further indicate that a combination of several antibody parameters
      (including titer, avidity, conformational dependence, and virus neutralization)
      are superior to any single antibody parameter as prognostic indicators to
      evaluate candidate AIDS vaccines.

PMID- 9188573
TI  - Stability of AML1 (core) site enhancer mutations in T lymphomas induced by
      attenuated SL3-3 murine leukemia virus mutants.
AB  - Murine retrovirus SL3-3 is highly T lymphomagenic. Its pathogenic properties are
      determined by the transcriptional enhancer of the U3 repeat region which shows
      preferential activity in T cells. Within the U3 repeats, the major determinant of
      T-cell specificity has been mapped to binding sites for the AML1 transcription
      factor family (also known as the core binding factor [CBF], polyomavirus enhancer
      binding protein 2 [PEBP2], and SL3-3 enhancer factor 1 [SEF-1]). SL3-3 viruses
      with AML1 site mutations have lost a major determinant of T-cell-specific
      enhancer function but have been found to retain a lymphomagenic potential,
      although disease induction is slower than for the SL3-3 wild type. To compare the
      specificities and mechanisms of disease induction of wild-type and mutant
      viruses, we have examined lymphomas induced by mutant viruses harboring
      transversions of three consecutive base pairs critical to AML1 site function (B.
      Hallberg, J. Schmidt, A. Luz, F. S. Pedersen, and T. Grundstrom. J. Virol.
      65:4177-4181, 1991). Our results show that the mutated AML1 sites are genetically
      stable during lymphomagenesis and that ecotropic provirus numbers in DNA of
      tumors induced by wild-type and mutant viruses fall within the same range.
      Moreover, proviruses were found to be integrated at the c-myc locus in similar
      proportions of wild-type and mutant SL3-3-induced tumors, and the mutated AML1
      sites of proviruses at c-myc are unaltered. In some cases, however, including one
      c-myc-integrated provirus, a single-base pair change was detected in a second,
      weaker AML1 binding site. By DNA rearrangement analysis of the T-cell receptor
      beta-locus, tumors induced by the AML1 site mutants are found to be of the T-cell
      type. Thus, although the AML1 site mutants have weakened T-cell-specific
      enhancers they are T-lymphomagenic, and wild-type- and mutant-virus-induced tumor
      DNAs are similar with respect to the number of overall ecotropic and c-myc
      integrated clonal proviruses. The SL3-3 wild-type and AML1 site mutant viruses
      may therefore induce disease by similar mechanisms.

PMID- 9188574
TI  - A mechanism for negative gene regulation in Autographa californica
      multinucleocapsid nuclear polyhedrosis virus.
AB  - The Autographa californica multinucleocapsid nuclear polyhedrosis virus (AcMNPV)
      ie-1 gene product (IE-1) is thought to play a central role in stimulating early
      viral transcription. IE-1 has been demonstrated to activate several early viral
      gene promoters and to negatively regulate the promoters of two other AcMNPV
      regulatory genes, ie-0 and ie-2. Our results indicate that IE-1 negatively
      regulates the expression of certain genes by binding directly, or as part of a
      complex, to promoter regions containing a specific IE-1-binding motif (5'
      ACBYGTAA-3') near their mRNA start sites. The IE-1 binding motif was also found
      within the palindromic sequences of AcMNPV homologous repeat (hr) regions that
      have been shown to bind IE-1. The role of this IE-1 binding motif in the
      regulation of the ie-2 and pe-38 promoters was examined by introducing mutations
      in these promoters in which the central 6 bp were replaced with BglII sites. GUS
      reporter constructs containing ie-2 and pe-38 promoter fragments with and without
      these specific mutations were cotransfected into Sf9 cells with various amounts
      of an ie-1-containing plasmid (pIe-1). Comparisons of GUS expression produced by
      the mutant and wild-type constructs demonstrated that the IE-1 binding motif
      mediated a significant decrease in expression from the ie-2 and pe-38 promoters
      in response to increasing pIe-1 concentrations. Electrophoretic mobility shift
      assays with pIe-1-transfected cell extracts and supershift assays with IE-1
      specific antiserum demonstrated that IE-1 binds to promoter fragments containing
      the IE-1 binding motif but does not bind to promoter fragments lacking this
      motif.

PMID- 9188575
TI  - Restoration of interferon responses of adenovirus E1A-expressing HT1080 cell
      lines by overexpression of p48 protein.
AB  - We have previously shown that both alpha interferon (IFN-alpha) and IFN-gamma
      signaling pathways are blocked in HeLa cells expressing the adenovirus E1A
      proteins (G. T. Leonard and G. C. Sen, Virology 224:25-33, 1996). Here, we report
      that in two other E1A-expressing cell lines derived from the HT1080 cells,
      neither IFN-alpha nor IFN-gamma could induce the transcription of genes
      containing the IFN-stimulated response element (ISRE). In contrast, IFN-gamma
      mediated signaling to the gamma-activated sequence was unimpaired in these cells.
      This dichotomy was due to a lowered level of functional p48 protein but not of
      STAT1 protein in the E1A-expressing HT1080 cells. When p48 was overexpressed in
      those cells by stably transfecting a p48 expression vector, both types of IFN
      could effectively induce the transcription of ISRE-driven genes. Consequently,
      IFN-alpha was highly effective in inhibiting the replication of
      encephelomyocarditis virus in the E1A-expressing cells, which also overexpressed
      p48. These results reinforce the general conclusion that adenovirus E1A proteins
      block IFN signaling pathways by lowering the functional levels of one or more
      components of the trans-acting complexes that activate the transcription of IFN
      stimulated genes.

PMID- 9188576
TI  - The product of the adenovirus intermediate gene IX is a transcriptional
      activator.
AB  - We have investigated the functional properties of the product of the adenovirus
      type 5 gene IX. This gene, which is expressed at intermediate times
      postinfection, encodes a small polypeptide (pIX) of 140 residues that has
      previously been shown to be incorporated into the viral capsid. Here, we show
      that pIX, in addition to its structural contribution, exhibits transcriptional
      properties. In transient transfection experiments, expression of pIX stimulated
      adenovirus major late promoter activity. The effect was independent of other
      viral proteins, but the level of promoter activation appeared strongly pIX dose
      dependent; similar levels of induction were observed with other cellular or viral
      TATA-containing (but not with TATA-less) promoters. This promoter specificity
      could be reproduced in a cell-free transcription system by the addition of
      purified recombinant pIX, further stressing the transcriptional nature of the
      phenomenon. A preliminary structural analysis of pIX indicated that the integrity
      of a putative leucine zipper at the carboxy-terminal end of the molecule, as well
      as elements within the amino-terminal half, was critical for pIX transcriptional
      activity. The relevance of these findings in adenovirus infection is discussed.

PMID- 9188577
TI  - Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic
      choriomeningitis virus-infected BALB/c mice.
AB  - The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus
      (LCMV) in BALB/c mice is predominantly directed against a single, Ld-restricted
      epitope in the viral nucleoprotein (residues 118 to 126). To investigate whether
      any Kd/Dd-restricted responses were activated but did not expand during the
      primary response, we used a BALB/c mutant, BALB/c-H-2dm2, which does not express
      the Ld molecule. Splenocytes from LCMV-infected BALB/c mice were transferred into
      irradiated BALB/c-H-2dm2 mice and rechallenged with LCMV. Thus, they were exposed
      to an antigenic stimulus without the involvement of the immunodominant Ld
      restricted epitope. In this adoptive transfer model, the donor splenocytes
      protected the recipient mice against chronic LCMV infection by mounting a potent
      Kd- and/or Dd-restricted secondary antiviral response. Analysis of a panel of Kd
      binding LCMV peptides revealed that residues 283 to 291 from the viral
      glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer
      model. Because the donor splenocytes were first activated during the primary
      infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in
      BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2dm2 mice. This
      study makes two points. First, it shows that subdominant CTL responses can be
      protective, and second, it provides a general experimental approach for
      uncovering subdominant CTL responses in vivo. This strategy can be used to
      identify subdominant T-cell responses in other systems.

PMID- 9188578
TI  - Tissue culture adaptation of foot-and-mouth disease virus selects viruses that
      bind to heparin and are attenuated in cattle.
AB  - Isolates of foot-and-mouth disease virus (FMDV) exist as complex mixtures of
      variants. Two different serotype O1 Campos preparations that we examined
      contained two variants with distinct plaque morphologies on BHK cells: a small,
      clear-plaque virus that replicates in BHK and CHO cells, and a large, turbid
      plaque virus that only grows in BHK cells. cDNAs encoding the capsids of these
      two variants were inserted into a genome-length FMDV type A12 infectious cDNA and
      used to produce chimeric viruses that exhibited the phenotype of the original
      variants. Analyses of these viruses, and hybrids created by exchanging portions
      of the capsid gene, identified codon 56 in VP3 (3056) as the critical determinant
      of both cell tropism and plaque phenotype. Specifically, the CHO growth/clear
      plaque phenotype is dependent on the presence of the highly charged Arg residue
      at 3056, and viruses with this phenotype and genotype were selected during
      propagation in tissue culture. The genetically engineered Arg 3056 virus was
      highly attenuated in bovines, but viruses recovered from animals inoculated with
      high doses of this virus had lost the ability to grow in CHO cells and contained
      either an uncharged residue at 3056 or a negatively charged Glu substituted for a
      Lys at a spatially and antigenically related position on VP2 (2134). Comparison
      of these animal-derived viruses to other natural and engineered viruses
      demonstrated that positively charged residues are required at both 2134 and 3056
      for binding to heparin. Taken together, these results indicate that in vitro
      cultivation of FMDV type O selects viruses that bind to heparin and that viruses
      with the heparin-binding phenotype are attenuated in the natural host.

PMID- 9188579
TI  - Transcriptional targeting of herpes simplex virus for cell-specific replication.
AB  - Tissue- or cell-specific targeting of vectors is critical to the success of gene
      therapy. We describe a novel approach to virus-mediated gene therapy, where viral
      replication and associated cytotoxicity are limited to a specific cell type by
      the regulated expression of an essential immediate-early viral gene product. This
      is illustrated with a herpes simplex virus type 1 (HSV-1) vector (G92A) whose
      growth is restricted to albumin-expressing cells. G92A was constructed by
      inserting an albumin enhancer/promoter-ICP4 transgene into the thymidine kinase
      gene of mutant HSV-1 d120, deleted for both copies of the ICP4 gene. This vector
      also contains the Escherichia coli lacZ gene under control of the thymidine
      kinase promoter, a viral early promoter, to permit easy detection of infected
      cells containing replicating vector. In the adult, albumin is expressed uniquely
      in the liver and in hepatocellular carcinoma and is transcriptionally regulated.
      The plaquing efficiency of G92A is > 10(3) times higher on human hepatoma cells
      than on non-albumin-expressing human cells. The growth kinetics of G92A in
      albumin-expressing cells is delayed compared with that of wild-type HSV-1, likely
      due to aberrant expression of ICP4 protein. Cells undergoing a productive
      infection expressed detectable levels of ICP4 protein, as well as the reporter
      gene product beta-galactosidase. Confining a productive, cytotoxic viral
      infection to a specific cell type should be useful for tumor therapy and the
      ablation of specific cell types for the generation of animal models of disease.

PMID- 9188580
TI  - Molecular basis for the differential subcellular localization of the 38- and 39
      kilodalton structural proteins of Borna disease virus.
AB  - Borna disease virus (BDV) is a nonsegmented negative-strand (NNS) RNA virus that
      is unusual because it replicates in the nucleus. The most abundant viral protein
      in infected cells is a 38/39-kDa doublet that is presumed to represent the
      nucleocapsid. Infectious particles also contain high levels of this protein,
      accounting for at least 50% of the viral proteins. The two forms of the protein
      differ by an additional 13 amino acids that are present at the amino terminus of
      the 39-kDa form and missing from the 38-kDa form. To examine whether this
      difference in amino acid content affects the localization of this protein in
      cells, the 39- and 38-kDa proteins were expressed in transfected cells. The 39
      kDa form was concentrated in the nucleus, whereas the 38-kDa form was found in
      both the nucleus and cytoplasm. Inspection of the extra 13 amino acids present in
      the 39-kDa form revealed a sequence (Pro-Lys-Arg-Arg) that is very similar to the
      nuclear localization signals (in both sequence homology and amino-terminal
      location) of the VP1 proteins of simian virus 40 and polyomavirus. Primer
      extension analysis of total RNA from infected cells suggests that there are two
      mRNA species encoding the two forms of the nucleocapsid protein. In infected
      cells, the 39-kDa form is expressed at about twofold-higher levels than the 38
      kDa form at both the RNA and protein levels. The novel nuclear localization of
      the 39-kDa nucleocapsid-like protein suggests that this form of the protein is
      targeted to the nucleus, the site for viral RNA replication, and that it may
      associate with genomic RNA.

PMID- 9188581
TI  - Biological characterization of human immunodeficiency virus type 1 clones derived
      from different organs of an AIDS patient by long-range PCR.
AB  - In order to characterize the biological properties of human immunodeficiency
      virus type 1 (HIV-1) variants from different tissues (peripheral blood
      mononuclear cells [PBMC], lymph node, spleen, brain, and lung) of one patient, we
      have chosen long-range PCR to amplify virtually full-length HIV proviruses and to
      construct replication-competent viruses by adding a patient-specific 5' long
      terminal repeat. To avoid selection during propagation in CD4+ target cells, we
      transfected 293 cells and used the supernatants from these cells as challenge
      viruses for tropism studies after titration on human PBMC. Despite differences in
      the V3 loop of the major variants found in brain and lung compared to lymphoid
      tissues all recombinant HIV clones obtained showed identical cell tropism and
      replicative kinetics. After infection of human PBMC these viruses replicated with
      similar kinetics, with a slow/low-titer, non-syncytium-inducing phenotype. In
      contrast to the prediction of macrophage tropism, drawn from the V3 loop
      sequence, none of these viruses infected monocyte-derived macrophages. The
      challenge of blood dendritic cells by these recombinant viruses in the presence
      of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor,
      and interleukin-4 resulted in a productive infection only after adding stimulated
      CD4+ T lymphocytes. Therefore, the biological properties of the HIV-1 variants
      derived from nonlymphoid tissue of this patient did not differ from those of HIV
      1 variants from lymphoid tissue with respect to tropism for primary cells such as
      PBMC, macrophages, and blood dendritic cells.

PMID- 9188582
TI  - Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals
      a novel aspect of coronavirus transcription.
AB  - We have inserted heterologous genetic material into the nonessential gene 4 of
      the coronavirus mouse hepatitis virus (MHV) in order to test the applicability of
      targeted RNA recombination for site-directed mutagenesis of the MHV genome
      upstream of the nucleocapsid (N) gene and to develop further genetic tools for
      site-directed mutagenesis of structural genes other than N. Initially, a 19
      nucleotide tag was inserted into the start of gene 4a of MHV strain A59 with the
      N gene deletion mutant Alb4 as the recipient virus. In further work, the entire
      gene for the green fluorescent protein (GFP) was inserted in place of gene 4,
      creating the currently largest known RNA virus. The expression of GFP was
      demonstrated by Western blot analysis of infected cell lysates; however, the
      level of GFP expression was not sufficient to allow detection of fluorescence of
      viral plaques. Northern blot analysis of transcripts of GFP recombinants showed
      the expected alteration of the pattern of the nested MHV subgenomic mRNAs.
      Surprisingly, though, GFP recombinants also produced an RNA species that was the
      same size as wild-type mRNA4. Analysis of the 5' end of this species revealed
      that it was actually a collection of mRNAs originating from 10 different genomic
      fusion sites, none possessing a canonical intergenic sequence. The finding of
      these aberrant mRNAs suggests that long-range RNA or the ribonucleoprotein
      structure of the MHV genome can sometimes be the sole determinant of the site of
      initiation of transcription.

PMID- 9188583
TI  - Characterization of late gene transcripts expressed during vegetative replication
      of human papillomavirus type 31b.
AB  - Human papillomaviruses (HPVs) are etiologic agents of anogenital cancers. The
      lack of an efficient in vitro system with which to study the differentiation
      dependent viral life cycle has impeded most investigations of viral transcription
      and gene expression. The CIN-612 clone 9E cell line latently maintains episomal
      copies of HPV type 31b (HPV31b). The complete replicative life cycle of HPV31b
      can be studied by using the organotypic (raft) culture system. A number of
      spliced HPV31b early gene transcripts and two late gene transcripts have been
      described in studies using the raft system. An HPV31b early promoter, P97, and a
      differentiation-induced promoter, P742, have been characterized by using this
      system. In this study, we used the raft system to analyze the temporal expression
      patterns of HPV31b late gene transcripts during the viral life cycle. The
      expression of late RNAs peaked at day 12 after lifting to the air-liquid
      interface; the levels then declined dramatically by day 16. The peak of late RNA
      expression was coincident with the appearance of virus particles in the raft
      tissues. We characterized transcripts with the potential to encode late gene
      products, including 19 RNAs containing the L1 region and 4 RNAs containing the
      E5b and L2 open reading frames. We also found evidence for two novel promoters.
      Transcription of both L1- and L2-containing RNAs initiated at a region upstream
      of the early promoter. In addition, late gene RNAs were also transcribed by using
      a promoter in the E4 reading frame.

PMID- 9188584
TI  - Specific cytotoxic T lymphocytes are involved in in vivo clearance of infectious
      bronchitis virus.
AB  - Cytotoxic T-lymphocyte (CTL) responses to infectious bronchitis virus (IBV) were
      determined at regular intervals between 3 and 30 days postinfection (p.i.). The
      maximum response with 82% lysis of labeled target cells was detected at 10 days
      p.i. The specific CTL response did not begin to decline until the amount of
      virus, which peaked at day 8 p.i. in both the kidneys and lungs, started to
      decrease. Clinical respiratory signs of illness also correlated with amount of
      virus. CTL activity was shown to be major histocompatibility complex (MHC) class
      restricted because the lysis of MHC-mismatched targets was negligible, and lysis
      was mediated by CD8+ CD4- T cells, as the CTL response could be abolished with
      removal of CD8+ CD4- but not CD4+ CD8- lymphocytes. In contrast, immunoglobulin M
      (IgM) antibody was not detected until day 10 p.i., and levels peaked at day 12
      p.i.; IgG antibody levels were minimal until day 15 p.i. but continued to
      increase exponentially until day 30 p.i., the last day examined. In summary, CTL
      responses correlated with initial decreases in infection and illness.

PMID- 9188586
TI  - Adenovirus vector-infected cells can escape adenovirus antigen-specific cytotoxic
      T-lymphocyte killing in vivo.
AB  - The recent findings that prolonged expression of certain adenovirus (Ad) vector
      encoded proteins, including human alpha1-antitrypsin (huAAT), mouse
      erythropoietin (EPO), and human factor IX, can be achieved in animals that do not
      mount an immune response to the reporter protein were obtained with mouse strains
      which have been shown to be capable of mounting a cellular immune response
      against Ad vector antigens. This suggests either that Ad vectors expressing
      nonimmunogenic transgenes fail to elicit a cellular immune response or that an Ad
      specific cellular immune response does develop but is ineffective against cells
      expressing nonimmunogenic transgenes. Here we demonstrate that an Ad vector
      expressing huAAT administered by intravenous injection does stimulate an Ad
      specific cellular immune response but that this response fails to abolish vector
      directed gene expression in vivo. Moreover, expression of huAAT remained stable
      in animals stimulated by concurrent and multiple administrations of different Ad
      vectors or viruses. We also demonstrate prolonged expression of huAAT in CD1 mice
      transgenic for the huAAT gene, indicating that long-term expression is not
      restricted to C57BL/6 mice. These results demonstrate that under some
      circumstances, an Ad vector can direct prolonged expression of a nonimmunogenic
      transgene despite the presence of a robust Ad-specific cellular immune response.

PMID- 9188585
TI  - Human immunodeficiency virus type 1 nucleocapsid protein promotes efficient
      strand transfer and specific viral DNA synthesis by inhibiting TAR-dependent self
      priming from minus-strand strong-stop DNA.
AB  - During the first strand transfer in reverse transcription, minus-strand strong
      stop DNA [(-) SSDNA] is annealed to the 3' end of the acceptor RNA in a reaction
      mediated by base-pairing between terminal repeat sequences in the RNA and their
      complement in the DNA. The large stem-loop structure in the repeat region known
      as TAR could interfere with this annealing reaction. We have developed an in
      vitro human immunodeficiency virus type 1 (HIV-1) system to investigate the
      effect of TAR on strand transfer. Mutational analysis demonstrates that the
      presence of TAR in the donor and acceptor templates inhibits strand transfer and
      is correlated with extensive synthesis of heterogeneous DNAs formed by self
      priming from (-) SSDNA. These DNAs are not precursors to the transfer product.
      Interestingly, products of self-priming are not detected in HIV-1 endogenous
      reactions; this suggests that virions contain a component which prevents self
      priming. Our results show that the viral nucleocapsid protein (NC), which can
      destabilize secondary structures, drastically reduces self-priming and
      dramatically increases the efficiency of strand transfer. In addition, the data
      suggest that the ability to eliminate self-priming is a general property of NC
      which is manifested during reverse transcriptase pausing at sites of secondary
      structure in the template. We conclude that this activity of NC is critical for
      achieving highly efficient and specific viral DNA synthesis. Our findings raise
      the possibility that inactivation of NC could provide a new approach for
      targeting reverse transcription in anti-HIV therapy.

PMID- 9188587
TI  - Self-association of herpes simplex virus type 1 ICP35 is via coiled-coil
      interactions and promotes stable interaction with the major capsid protein.
AB  - The ordered copolymerization of viral proteins to form the herpes simplex virus
      (HSV) capsid occurs within the nucleus of the infected cell and is a complex
      process involving the products of at least six viral genes. In common with capsid
      assembly in double-stranded DNA bacteriophages, HSV capsid assembly proceeds via
      the assembly of an outer capsid shell around an interior scaffold. This capsid
      intermediate matures through loss of the scaffold and packaging of the viral
      genomic DNA. The interior of the HSV capsid intermediate contains the viral
      protease and assembly protein which compose the scaffold. Proteolytic processing
      of these proteins is essential for and accompanies capsid maturation. The
      assembly protein (ICP35) is the primary component of the scaffold, and previous
      studies have demonstrated it to be capable of intermolecular association with
      itself and with the major capsid protein, VP5. We have defined structural
      elements within ICP35 which are responsible for intermolecular self-association
      and for interaction with VP5. Yeast (Saccharomyces cerevisiae) two-hybrid assays
      and far-Western studies with purified recombinant ICP35 mapped a core self
      association domain between Ser165 and His219. Site-directed mutations in this
      domain implicate a putative coiled coil in ICP35 self-association. This coiled
      coil motif is highly conserved within the assembly proteins of other alpha
      herpesviruses. In the two-hybrid assay the core self-association domain was
      sufficient to mediate stable self-association only in the presence of additional
      structural elements in either N- or C-terminal flanking regions. These regions
      also contain conserved sequences which exhibit a high propensity for alpha
      helicity and may contribute to self-association by forming additional short
      coiled coils. Our data supports a model in which ICP35 molecules have an extended
      conformation and associate in parallel orientation through homomeric coiled-coil
      interactions. In additional two-hybrid experiments we evaluated ICP35 mutants for
      association with VP5. We discovered that in addition to the C-terminal 25 amino
      acids of ICP35, previously shown to be required for VP5 binding, an additional
      upstream region was required. This region is between Ser165 and His234 and
      contains the core self-association domain. Site-directed mutations and
      construction of chimeric molecules in which the self-association domain of ICP35
      was replaced by the GCN4 leucine zipper indicated that this region contributes to
      VP5 binding through mediating self-association of ICP35 and not through direct
      binding interactions. Our results suggest that self-association of ICP35 strongly
      promotes stable association with VP5 in vivo and are consistent with capsid
      formation proceeding via formation of stable subassemblies of ICP35 and VP5 which
      subsequently assemble into capsid intermediates in the nucleus.

PMID- 9188588
TI  - Plasma membrane targeting of chimeric intracisternal A-type particle polyproteins
      leads to particle release and specific activation of the viral proteinase.
AB  - Retrovirus morphogenesis involves assembly of structural Gag polyproteins with
      subsequent budding from the plasma membrane, followed by proteolytic cleavage by
      the viral proteinase (PR) and extracellular maturation to the infectious virion.
      Intracisternal A-type particles (IAPs) are defective retroviruses that assemble
      and bud at the membranes of the endoplasmic reticulum (ER), where they remain as
      immature particles consisting exclusively of uncleaved polyproteins. To analyze
      requirements for intracellular polyprotein transport and PR activation, we
      constructed deletion and substitution mutations in the IAP gag gene, including
      the putative ER-targeting signal. Mutant polyproteins were transported to various
      intracellular locations, including the nucleus, the cytoplasm, the ER, and the
      plasma membrane. Interestingly, assembly of capsid-like particle structures
      occurred at almost all sites. However, only those polyproteins transported to the
      plasma membrane were efficiently and specifically cleaved by viral PR, with
      cleavage occurring predominantly within the virus particle. Thus, at least in the
      experimental system presented here, retroviral particle assembly can occur at
      almost any location within the cell, while polyprotein processing and,
      consequently, virion maturation are confined to a specific cellular site. These
      results suggest that a factor restricted to the plasma membrane is required to
      trigger PR activation and maturation of infectious retroviruses.

PMID- 9188589
TI  - Identification and analysis of three myristylated vaccinia virus late proteins.
AB  - Previous studies have shown that at least three vaccinia virus (VV) late proteins
      (with apparent molecular asses of 37, 35, and 25 kDa) label with myristic acid.
      Time course labeling of VV-infected cells with [3H]myristic acid reveals at least
      three additional putative myristylproteins, with apparent molecular masses of 92,
      17, and 14 kDa. The 25-kDa protein has previously been identified as that encoded
      by the L1R open reading frame, leaving the identities of the remaining proteins
      to be determined. Sequence analysis led to the preliminary identification of the
      37-, 35-, and 17-kDa proteins as G9R, A16L, and E7R, respectively. Using
      synthetic oligonucleotides and PCR techniques, each of these open reading frames
      was amplified by using VV DNA as a template and then cloned individually into
      expression vectors behind T7 promoters. These plasmid constructs were then
      transcribed in vitro, and the resulting mRNAs were translated in wheat germ
      extracts and radiolabeled with either [35S]methionine or [3H]myristic acid. Each
      wild-type polypeptide was labeled with [35S]methionine or [3H]myristic acid in
      the translation reactions, while mutants containing an alanine in place of
      glycine at the N terminus were labeled only with [35S]methionine, not with
      myristic acid. This result provided strong evidence that the open reading frames
      had been correctly identified and that each protein is myristylated on a glycine
      residue adjacent to the initiating methionine. Subcellular fractionations of VV
      infected cells suggested that A16L and E7R are soluble, in contrast to L1R, which
      is a membrane-associated protein.

PMID- 9188590
TI  - Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral
      effect of nitric oxide on RNA virus replication.
AB  - The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV),
      a member of the family Flaviviridae, were investigated in this study. In vitro,
      inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine
      macrophages was correlated to cellular NO production. When cocultured with
      infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7
      cells also efficiently hindered JEV replication in contiguous bystanders, and
      this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N
      monomethyl-L-arginine acetate. In vivo, the mortality rate increased as the NOS
      activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro
      L-arginine methyl ester. Moreover, when an organic donor, S-nitro-N
      acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also
      observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as
      well as in persistently JEV-infected C2-2 cells. These data reaffirm that NO has
      an effective and broad-spectrum antimicrobial activity against diversified
      intracellular pathogens. Interestingly, the antiviral effect of NO was not
      enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure
      which has been shown to greatly increase the antiviral effect of NO in infection
      by vesicular stomatitis virus. From biochemical analysis of the impact of NO on
      JEV replication in cell culture, NO was found to profoundly inhibit viral RNA
      synthesis, viral protein accumulation, and virus release from infected cells. The
      results herein thus suggest that NO may play a crucial role in the innate
      immunity of the host to restrict the initial stage of JEV infection in the
      central nervous system.

PMID- 9188591
TI  - Role for highly regulated rep gene expression in adeno-associated virus vector
      production.
AB  - Recent success achieving long-term in vivo gene transfer without a significant
      immune response by using adeno-associated virus (AAV) vectors (X. Xiao, J. Li,
      and R. J. Samulski, J. Virol. 70:8098-8108, 1996) has encouraged further
      development of this vector for human gene therapy. Currently, studies focus on
      the generation of high-titer vectors by using the two-plasmid helper-vector
      system in adenovirus (Ad)-infected cells. To examine the effects of the AAV
      replication (rep) genes on recombinant AAV (rAAV) vector production, we have
      constructed a series of AAV helper plasmids that contain strong heterologous
      promoters in place of the endogenous p5 promoter. Although high-level rep gene
      expression was achieved, rAAV DNA failed to replicate in the absence of Ad
      infection. Moreover, unregulated overexpression of Rep78/68 led to substantially
      lower rAAV yields in the presence of Ad (10(4-5) versus 10(7-8)). In contrast,
      under similar conditions, reduced Rep78/68 expression resulted in much higher
      rAAV yields (10(9)). Molecular characterization showed that overexpression of the
      rep gene decreased rAAV DNA replication and severely inhibited capsid (cap) gene
      expression. Interestingly, a reduced rep level enhanced cap gene expression and
      supported normal rAAV DNA replication. These studies suggest a critical role for
      regulated rep gene expression in rAAV production and have facilitated the
      development of a new AAV helper plasmid that increases vector production
      eightfold over currently used constructs.

PMID- 9188592
TI  - Brain-infiltrating cytolytic T lymphocytes specific for Theiler's virus recognize
      H2Db molecules complexed with a viral VP2 peptide lacking a consensus anchor
      residue.
AB  - Mice expressing the H2b haplotype are resistant to infection with Theiler's
      murine encephalomyelitis virus (TMEV), which causes chronic demyelination in
      susceptible mice. The prominent cytolytic T-lymphocyte (CTL) response to the VP2
      antigen encoded by TMEV led us to the identification of a class I-binding peptide
      derived from the VP2 antigen. Escherichia coli transformants overexpressing a
      series of 11 overlapping VP2 protein fragments were subjected to lysis and alkali
      digestion, and the resultant peptide pools were tested for their abilities to
      sensitize RMA-S targets for lysis by CTLs. The source of effector CD8+ T cells
      for the assays was either freshly harvested central nervous system-infiltrating
      lymphocytes (CNS-IL) or CNS-IL-derived VP2-specific CTL clones and lines. A 10
      residue peptide at VP2 positions 121 to 130 (VP2(121-130)) (FHAGSLLVFM) was
      identified that sensitized targets for lysis and formed stable complexes with
      H2Db class I molecules. The VP2(121-130) peptide sensitized target cells for
      lysis by freshly harvested CNS-IL CTLs at femtomolar concentrations. Despite its
      relative high level of biological activity, the VP2(121-130) peptide is
      distinguished from other Db-binding peptides by its lack of an asparagine residue
      at position five, which had been previously proposed to be a requirement for Db
      peptide complexing.

PMID- 9188593
TI  - Interference of coronavirus infection by expression of immunoglobulin G (IgG) or
      IgA virus-neutralizing antibodies.
AB  - Immunoglobulin gene fragments encoding the variable modules of the heavy and
      light chains of a transmissible gastroenteritis coronavirus (TGEV)-neutralizing
      monoclonal antibody (MAb) have been cloned and sequenced. The selected MAb
      recognizes a highly conserved viral epitope and does not lead to the selection of
      neutralization escape mutants. The sequences of MAb 6A.C3 kappa and gamma 1
      modules were identified as subgroup V and subgroup IIIC, respectively. The
      chimeric immunoglobulin genes encoding the variable modules from the murine MAb
      and constant modules of human gamma 1 and kappa chains were constructed by
      reverse transcriptase PCR. Chimeric immunoglobulins were stably or transiently
      expressed in murine myelomas or COS cells, respectively. The secreted recombinant
      antibodies had radioimmunoassay titers (i.e., the highest dilution giving a
      threefold increase over the background) higher than 10(3) and reduced the
      infectious virus more than 10(4)-fold. Recombinant dimeric immunoglobulin A (IgA)
      showed a 50-fold enhanced neutralization of TGEV relative to a recombinant
      monomeric IgG1 which contained the identical antigen binding site. Stably
      transformed epithelial cell lines which expressed either recombinant IgG or IgA
      TGEV-neutralizing antibodies reduced virus production by > 10(5)-fold after
      infection with homologous virus, although a residual level of virus production (<
      10(2) PFU/ml) remained in less than 0.1% of the cells. This low-level persistent
      infection was shown not to be due to the selection of neutralization escape
      mutants. The implications of these findings for somatic gene therapy with
      recombinant antibodies are discussed.

PMID- 9188594
TI  - The Vif and Gag proteins of human immunodeficiency virus type 1 colocalize in
      infected human T cells.
AB  - The Vif protein of human immunodeficiency virus type 1 (HIV-1) and other
      lentiviruses is required for efficient replication in primary cells and certain
      immortalized cell lines in vitro and, in all likelihood, for the establishment of
      pathogenic infections in vivo. Current hypotheses concerning Vif's mechanism of
      action posit that it operates in virus-expressing cells during virion assembly,
      budding, or maturation such that released virions are modified in a manner that
      enables them to undergo productive infection in subsequent viral challenges. To
      gain further insight into the mechanism of action of lentivirus Vif proteins, we
      have performed a variety of in situ localization and biochemical fractionation
      studies using cells in which Vif is essential for efficient replication. Double
      label immunofluorescence analyses of cells productively infected with HIV-1 or
      feline immunodeficiency virus revealed dramatic patterns of colocalization
      between Vif and the virally encoded Gag proteins. Subcellular fractionations of
      human T cells expressing HIV-1 Vif performed in the absence of any detergent
      demonstrated that greater than 90% of Vif is associated with cellular membranes.
      Additional purification using a continuous density gradient indicated that the
      majority of the membrane-bound Vif copurifies with the plasma membrane. Taken
      together, these observations suggest that lentivirus Vif and Gag proteins
      colocalize at the plasma membrane as virion assembly and budding take place. As a
      result, Vif is able to exert its modulatory effect(s) on these late steps of the
      virus life cycle.

PMID- 9188596
TI  - Hemagglutinin-esterase, a novel structural protein of torovirus.
AB  - We have characterized the 3'-most 3 kb of the genome of bovine torovirus (BoTV)
      strain Breda. A novel 1.2-kb gene, located between the genes for the membrane and
      nucleocapsid proteins, was identified. This gene, the 3'-most 0.5 kb of which is
      also present in the genome of the equine torovirus isolate Berne virus (BEV),
      codes for a class I membrane protein displaying 30% sequence identity with the
      hemagglutinin-esterases (HEs) of coronaviruses and influenza C viruses.
      Heterologous expression of the BoTV HE gene yielded a 65,000-molecular weight N
      glycosylated protein displaying acetylesterase activity. Serologic evidence
      indicates that the HE homolog is expressed during the natural infection and
      represents a prominent antigen. By using an antiserum raised against residues 13
      to 130 of HE, the HE protein was detected in radioiodinated, sucrose gradient
      purified BoTV preparations. Formal evidence that HE is a structural protein was
      provided by immunoelectron microscopy. In addition to the large, 17- to 20-nm
      spikes, BoTV virions possess shorter surface projections (6 nm on average). We
      postulate that these surface projections, which are absent from the BEV virion,
      are composed of the BoTV HE homolog. The HE gene, which has now been demonstrated
      in three different virus genera, is a showpiece example of modular evolution.

PMID- 9188595
TI  - Gene expression during reactivation of herpes simplex virus type 1 from latency
      in the peripheral nervous system is different from that during lytic infection of
      tissue cultures.
AB  - Herpes simplex virus (HSV) replicates in peripheral tissues and forms latent
      infections in neurons of the peripheral nervous system. It can be reactivated
      from latency by various stimuli to cause recurrent disease. During lytic
      infection in tissue culture cells, there is a well-described temporal pattern of
      (i) immediate-early, (ii) early, and (iii) late gene expression. However, latency
      is characterized by little if any expression of genes of the lytic cycle of
      infection. During reactivation, the pattern of gene expression is presumed to be
      similar to that during the lytic cycle in tissue culture, though recent work of
      W. P. Halford et al. (J. Virol. 70:5051-5060, 1996) and P. F. Nichol et al. (J.
      Virol. 70:5476-5486, 1996) suggests that it is modified in neuronal cell
      cultures. We have used the mouse trigeminal ganglion explant model and reverse
      transcription-PCR to determine the pattern of viral and cellular gene expression
      during reactivation. Surprisingly, the pattern of viral gene expression during
      lytic infection of cell cultures is not seen during reactivation. During
      reactivation, early viral transcripts were detected before immediate-early
      transcripts. The possibility that a cellular factor upregulates early genes
      during the initial reactivation stimulus is discussed.

PMID- 9188597
TI  - Neurologic disease induced by polytropic murine retroviruses: neurovirulence
      determined by efficiency of spread to microglial cells.
AB  - Several murine leukemia viruses (MuLV) induce neurologic disease in susceptible
      mice. To identify features of central nervous system (CNS) infection that
      correlate with neurovirulence, we compared two neurovirulent MuLV, Fr98 and
      Fr98/SE, with a nonneurovirulent MuLV, Fr54. All three viruses utilize the
      polytropic receptor and are coisogenic, each containing a different envelope gene
      within a common genetic background. Both Fr98 and Fr98/SE induce a clinical
      neurologic disease characterized by hyperexcitability and ataxia yet differ in
      incubation period, 16 to 30 and 30 to 60 days, respectively. Fr54 infects the CNS
      but fails to induce clinical signs of neurologic disease. In this study, we
      compared the histopathology, regional virus distribution, and cell tropism in the
      brain, as well as the relative CNS viral burdens. All three viruses induced
      similar histopathologic effects, characterized by intense reactive astrogliosis
      and microglial activation associated with minimal vacuolar degeneration. The
      infected target cells for each virus consisted primarily of endothelial and
      microglial cells, with rare oligodendrocytes. Infection localized predominantly
      in white matter tracts of the cerebellum, internal capsule, and corpus callosum.
      The only feature that correlated with relative neurovirulence was viral burden as
      measured by both viral CA protein expression in cerebellar homogenates and
      quantification of infected cells. Interestingly, Fr54 (nonneurovirulent) and
      Fr98/SE (slow disease) had similar viral burdens at 3 weeks postinoculation,
      suggesting that they entered the brain with comparable efficiencies. However,
      spread of Fr98/SE within the brain thereafter exceeded that of Fr54, reaching
      levels of viral burden comparable to that seen for Fr98 (rapid disease) at 3
      weeks. These results suggest that the determinants of neurovirulence in the
      envelope gene may influence the efficiency of virus spread within the brain and
      that a critical number of infected cells may be required for induction of
      clinical neurologic disease.

PMID- 9188599
TI  - Cloning of the rainbow trout (Oncorhynchus mykiss) Mx2 and Mx3 cDNAs and
      characterization of trout Mx protein expression in salmon cells.
AB  - Two rainbow trout (Oncorhynchus mykiss) Mx cDNAs were cloned by using RACE (rapid
      amplification of cDNA ends) PCR and were designated RBTMx2 and RBTMx3. The
      deduced RBTMx2 and RBTMx3 proteins were 636 and 623 amino acids in length with
      molecular masses of 72 and 70.8 kDa, respectively. These proteins, along with the
      previously described RBTMx1 protein (G. D. Trobridge and J. A. Leong, J.
      Interferon Cytokine Res. 15:691-702, 1995), have between 88.7 and 96.6% identity
      at the amino acid level. All three proteins contain the tripartite GTP binding
      domain and leucine zipper motif common to Mx proteins. A monospecific polyclonal
      antiserum to an Escherichia coli-expressed fragment of RBTMx3 was generated, and
      that reagent was found to react with all three rainbow trout Mx proteins.
      Subsequently, endogenous Mx production in RTG-2 cells induced with poly(IC)
      double-stranded RNA was detected by immunoblot analysis. The cellular
      localization of the rainbow trout proteins was determined by transient expression
      of the RBTMx cDNAs in CHSE-214 (chinook salmon embryo) cells. A single-cell
      transient-transfection assay was used to examine the ability of each Mx cDNA
      clone to inhibit replication of the fish rhabdovirus infectious hematopoietic
      necrosis virus (IHNV). No significant inhibition in the accumulation of the IHNV
      nucleoprotein was observed in cells expressing either trout Mx1, Mx2, or Mx3 in
      transiently transfected cells.

PMID- 9188598
TI  - Characterization of humoral and CD4+ cellular responses after genetic
      immunization with retroviral vectors expressing different forms of the hepatitis
      B virus core and e antigens.
AB  - The humoral and CD4+ cellular immune responses in mice following genetic
      immunization with three retroviral vectors encoding different forms of hepatitis
      B virus core antigen (HBcAg) and e antigen (HBeAg) were analyzed. The retroviral
      vectors induced expression of intracellular HBcAg (HBc[3A4]), secreted HBeAg
      (HBe[5A2]), or an intracellular HBcAg-neomycin phosphoryltransferase fusion
      protein (HBc-NEO[6A3]). Specific antibody levels and immunoglobulin G isotype
      restriction were highly dependent on both the host major histocompatibility
      complex and the transferred gene. Humoral and CD4+ cellular HBcAg and/or HBeAg
      (HBc/eAg)-specific immune responses following retroviral vector immunization were
      of a lower magnitude but followed the same characteristics compared with those
      after immunization with HBc/eAg in adjuvant. Two factors influenced the humoral
      responses. First, in vivo depletion of CD8+ cells in HBc-NEO[6A3]-immunized H-2k
      mice abrogated both HBcAg-specific antibodies and in vitro-detectable cytotoxic T
      lymphocytes. Second, priming of H-2b mice with an HBc/eAg-derived T-helper (Th)
      peptide in adjuvant prior to retroviral vector immunization greatly enhanced the
      HBc/eAg-specific humoral responses to all three vectors, suggesting that
      insufficient HBc/eAg-specific CD4+ Th-cell priming limits the humoral responses.
      In conclusion, direct injection of retroviral vectors seems to be effective in
      priming HBc/eAg-specific CD8+ but comparatively inefficient in priming CD4+ Th
      cells and subsequently specific antibodies. However, the limited HBc/eAg-specific
      CD4+ cell priming can effectively be circumvented by prior administration of a
      recombinant or synthetic form of HBc/eAg in adjuvant.

PMID- 9188601
TI  - The NS1 protein of the autonomous parvovirus minute virus of mice blocks cellular
      DNA replication: a consequence of lesions to the chromatin?
AB  - The nonstructural protein NS1 of the autonomous parvovirus minute virus of mice
      interferes with cell division and can cause cell death, depending on the cell
      transformation state. Upon infection, the synthesis of NS1 protein is massively
      initiated during S phase. In this article, we show that minute virus of mice
      infected cells accumulate in this phase. To investigate the link between NS1
      accumulation and S-phase arrest, we have used stably transfected cells in which
      NS1 expression is under the control of a glucocorticoid-inducible promoter (the
      long terminal repeat of mouse mammary tumor virus). NS1 expression interferes
      with cell DNA replication, and consequently, the cell cycle stops in S phase. NS1
      expression also induces nicks in the cell chromatin, as detected by an in situ
      nick translation assay. The nicks are observed several hours before any cell
      cycle perturbation. As cell cycle arrest is a common consequence of DNA damage,
      we propose that NS1 exerts its cytostatic activity by inducing lesions in cell
      chromatin.

PMID- 9188600
TI  - Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites,
      cofactor requirements, and molecular model of an enzyme essential for pestivirus
      replication.
AB  - Members of the Flaviviridae encode a serine proteinase termed NS3 that is
      responsible for processing at several sites in the viral polyproteins. In this
      report, we show that the NS3 proteinase of the pestivirus bovine viral diarrhea
      virus (BVDV) (NADL strain) is required for processing at nonstructural (NS)
      protein sites 3/4A, 4A/4B, 4B/5A, and 5A/5B but not for cleavage at the junction
      between NS2 and NS3. Cleavage sites of the proteinase were determined by amino
      terminal sequence analysis of the NS4A, NS4B, NS5A, and NS5B proteins. A
      conserved leucine residue is found at the P1 position of all four cleavage sites,
      followed by either serine (3/4A, 4B/5A, and 5A/5B sites) or alanine (4A/4B site)
      at the P1' position. Consistent with this cleavage site preference, a structural
      model of the pestivirus NS3 proteinase predicts a highly hydrophobic P1
      specificity pocket. trans-Processing experiments implicate the 64-residue NS4A
      protein as an NS3 proteinase cofactor required for cleavage at the 4B/5A and
      5A/5B sites. Finally, using a full-length functional BVDV cDNA clone, we
      demonstrate that a catalytically active NS3 serine proteinase is essential for
      pestivirus replication.

PMID- 9188602
TI  - Long-lasting adenovirus transgene expression in mice through neonatal intrathymic
      tolerance induction without the use of immunosuppression.
AB  - The major barrier to the clinical application of adenovirus gene therapy for
      diseases that require stable transgene expression is the immunogenicity of
      recombinant adenovirus, which ordinarily limits the duration of its effects to a
      period of about 2 weeks. We postulated that tolerance to adenovirus could be
      induced and transgene expression could be prolonged if T lymphocytes underwent
      thymic selection in the presence of adenovirus antigens. Mice were inoculated in
      the thymus with a recombinant adenovirus containing the lacZ marker gene during
      the neonatal period at a time before T-cell maturation had occurred. When the
      virus was administered intravenously to these mice in adulthood, they were found
      to have an impaired adenovirus-specific cytotoxic T-lymphocyte response which
      allowed prolonged hepatic lacZ expression, for up to 260 days. The ability to
      achieve unresponsiveness to a recombinant adenovirus after inoculation of the
      thymus in neonates extends the paradigm of intrathymic tolerance induction.
      Furthermore, this model will enable the study of stable adenovirus transgene
      expression in vivo without the use of immunosuppression and ultimately may have
      clinical utility.

PMID- 9188603
TI  - cis-Acting sequences in addition to donor and acceptor sites are required for
      template switching during synthesis of plus-strand DNA for duck hepatitis B
      virus.
AB  - A characteristic of all hepadnaviruses is the relaxed-circular conformation of
      the DNA genome within an infectious virion. Synthesis of the relaxed-circular
      genome by reverse transcription requires three template switches. These template
      switches, as for the template switches or strand transfers of other reverse
      transcribing genetic elements, require repeated sequences (the donor and acceptor
      sites) between which a complementary strand of nucleic acid is transferred. The
      mechanism for each of the template switches in hepadnaviruses is poorly
      understood. To determine whether sequences other than the donor and acceptor
      sites are involved in the template switches of duck hepatitis B virus (DHBV), a
      series of molecular clones which express viral genomes bearing deletion mutations
      were analyzed. We found that three regions of the DHBV genome, which are distinct
      from the donor and acceptor sites, are required for the synthesis of relaxed
      circular DNA. One region, located near the 3' end of the minus-strand template,
      is required for the template switch that circularizes the genome. The other two
      regions, located in the middle of the genome and near DR2, appear to be required
      for plus-strand primer translocation. We speculate that these cis-acting
      sequences may play a role in the organization of the minus-strand DNA template
      within the capsid particle so that it supports efficient template switching
      during plus-strand DNA synthesis.

PMID- 9188604
TI  - Insertions within epsilon affect synthesis of minus-strand DNA before the
      template switch for duck hepatitis B virus.
AB  - Duck hepatitis B virus (DHBV) is a DNA virus that replicates via reverse
      transcription of a pregenomic RNA (pgRNA). Synthesis of the first strand of DNA
      (minus-strand DNA) for DHBV can be divided into two steps: (i) synthesis of the
      first four nucleotides of minus-strand DNA, which is primed by the viral
      polymerase (P) protein and copied from the sequence 5'-UUAC-3' within the
      phylogenetically conserved bulge in the encapsidation signal (epsilon) near the
      5' end of pgRNA; and (ii) a template switch of the four-nucleotide minus-strand
      DNA from epsilon to an acceptor site near the 3' end of pgRNA and synthesis of a
      complete minus-strand DNA. To understand why only four nucleotides of minus
      strand DNA were synthesized before the template switch, we introduced small
      insertions immediately 5' to the UUAC sequence in epsilon and determined whether
      these epsilon variants were competent for protein priming and whether minus
      strands longer than four nucleotides were synthesized. Then we determined, in
      cell culture, whether the longer minus-strand DNAs were competent to undergo a
      template switch. Also, we analyzed the structure of the epsilon variants, in
      solution. We found that the epsilon variants were functional for protein priming
      and RNA encapsidation and that the insertions were copied into minus-strand DNA.
      However, two mutant viruses that contained two different three-nucleotide
      insertions failed to synthesize minus-strand DNA efficiently from the acceptor
      site, even though seven nucleotides of the donor and acceptor sites were
      identical. These results suggest that the length and/or sequence of the minus
      strand DNA copied from epsilon can be important for an efficient template switch.
      The RNA structural analysis of the epsilon variants indicated alteration in the
      position and size of the bulge. Overall, these results are consistent with the
      notion that the template within epsilon is limited to four nucleotides because
      the remaining two nucleotides located within the bulge are inaccessible for
      polymerization.

PMID- 9188605
TI  - Characterization of glycosylated Gag expressed by a neurovirulent murine leukemia
      virus: identification of differences in processing in vitro and in vivo.
AB  - The neuroinvasiveness of a chimeric murine retrovirus, CasFrKP (KP), is dependent
      on the expression of glycosylated Gag (gp85gag). This viral protein is the
      product of alternate translation initiation 88 codons upstream of and in frame
      with the initiation codon of pr65gag, the precursor of the viral core proteins.
      Although expression of glycosylated Gag affects virus spread in the spleen, it
      appears not to affect virus spread in vitro in fibroblast cell lines (J. L.
      Portis et al., J. Virol. 68:3879-3887, 1994). The differential effects of this
      protein in vitro and in vivo have not been explained, and its function is
      unknown. We have here compared the in vitro processing of this molecule with that
      expressed in spleens of infected mice. In vitro, gp85gag was cleaved near the
      middle of the molecule, releasing the C-terminal half (containing capsid and
      nucleocapsid domains of pr65gag) as a secreted glycoprotein. The N-terminal half
      of the protein was associated with the plasma membrane as a approximately 55-kDa
      glycoprotein bearing the matrix domain of pr65gag as well as the N-terminal 88
      residue L domain. This processing scheme was also observed in vivo, although two
      differences were seen. There were differences in N-linked glycosylation of the
      secreted form of the protein expressed in the spleen. In addition, whereas the
      membrane-associated species assumed the orientation of a type II integral
      membrane protein (N(cyto) C(exo)) in fibroblasts in vitro, a subpopulation of
      spleen cells was detected in which the N terminus of the protein was exposed at
      the cell surface. These results suggest that the differential effects of
      glycosylated Gag expression in vivo and in vitro may be related to differences in
      posttranslational processing of the protein.

PMID- 9188606
TI  - Theiler's virus and Mengo virus induce cross-reactive cytotoxic T lymphocytes
      restricted to the same immunodominant VP2 epitope in C57BL/6 mice.
AB  - C57BL/6 mice develop a virus-specific cytotoxic T-lymphocyte (CTL) response after
      intraperitoneal inoculation with either the DA strain of Theiler's virus or Mengo
      virus, two members of the Cardiovirus genus. These CTLs contribute to viral
      clearance in the case of Theiler's virus but do not protect the mice from the
      fatal encephalomyelitis caused by Mengo virus. In this study we show that DA and
      Mengo virus-induced CTLs are cross-reactive. The cross-reactivity is due to a
      conserved, H-2Db-restricted epitope located between amino acid residues 122 and
      130 of the VP2 capsid protein (VP2(122-130)). This epitope is immunodominant in
      C57BL/6 mice infected with Theiler's virus. The VP2(122-130) epitope, initially
      identified for Mengo virus, is the first CTL epitope described for Theiler's
      virus.

PMID- 9188607
TI  - Infectious RNA transcripts from full-length dengue virus type 2 cDNA clones made
      in yeast.
AB  - The dengue virus type 2 genomic RNA was amplified by reverse transcription-PCR
      and cloned as four cDNA fragments. We could not assemble these four fragments
      into full-length cDNA in Escherichia coli. The full-length dengue virus cDNA was
      constructed by homologous recombination in yeast, either as part of a yeast
      artificial chromosome or in a yeast-E. coli shuttle vector. Full-length cDNA
      clones were propagated once in E. coli to prepare useful quantities of DNA. In
      vitro transcription of these clones produced full-length RNA transcripts.
      Introduction of these transcripts into LLC-MK2 cells produced typical dengue
      infection, as judged by cytopathic effects and indirect immunofluorescence.
      Infectivity was sensitive to RNase digestion and was dependent on the presence of
      cap analog in the transcription reaction mixture. Virus in the medium was
      passaged on C6-36 cells to produce stocks, and these stocks had titers and plaque
      morphologies similar to those of the parental dengue virus type 2. Intracellular
      dengue virus RNA from cells infected with transcript-derived virus contained an
      introduced BstEII site, proving that infectivity was derived from RNA transcripts
      and not from contamination with parental dengue virus. Transcript-derived virus
      was comparable to dengue virus type 2 for growth and protein expression in tissue
      culture cells. Sequence analysis of the dengue virus cDNA in one full-length
      clone revealed only one unexpected silent mutation. By using yeast technology, it
      will be easy to introduce specific mutations into the dengue virus cDNA, allowing
      analysis of the virus phenotype in cells transfected with mutant transcripts.

PMID- 9188608
TI  - High level of transgene expression in cell cultures and in the mouse by
      replication-incompetent adenoviruses harboring modified VAI genes.
AB  - Replication-incompetent adenoviruses are currently used in gene therapy trials.
      Most of the work designed to increase the expression from these vectors concerns
      the modification of cis sequences of the foreign transcription unit, so as to
      improve the transcription level or the stability of the mRNA. In this report, we
      show that an alternative strategy based on the coexpression of modified VAI genes
      can efficiently increase gene expression both in cell cultures and in animals.
      The VAI RNA is synthesized mainly during the late phase of the adenovirus cycle
      and increases the translation of late adenovirus gene products by counteracting
      the effect of an interferon-induced kinase, the PKR. We have constructed several
      modified VAI genes in which the central domain was deleted or substituted by
      exogenous sequences. These modified VAI genes, or the native VAI gene, were
      cloned into the left part of adenovirus type 5 genomes harboring their own
      endogenous VAI gene. One of the resulting viruses (Ad-VAr) increased 12.5- to 502
      fold the expression level of reporter genes, either expressed as a constitutive
      cell line from an extrachromosomal DNA or introduced into cells by coinfection
      with another adenovirus vector. This effect was independent of the promoter, the
      coding sequence, and the 5' untranslated mRNA sequence and was obvious in the two
      non-E1-complementing cell lines tested (HeLa and Vero). Coinfection of Ad-VAr
      with adenoviruses expressing the luciferase gene from the major late promoter or
      Rous sarcoma virus (RSV) promoter by the intravenous route in mice increased by
      more than 33 (MLP)- to 128 (RSV)- and 4,700 (MLP)- to 30,000 (RSV)-fold the
      expression level of the reporter gene in the lungs and liver, respectively. The
      intramuscular coinoculation of Ad-VAr and Ad-MLP-gD (a recombinant adenovirus
      vaccine expressing gD from the pseudorabies herpes virus) led to a 10-fold
      decrease in the protective dose of Ad-gD in mice. Ad-VAfull, a similar adenovirus
      in which the native VAI gene was cloned at the left part of the genome, showed no
      evidence of efficacy in cell culture and in mice. These results suggest that the
      use of modified VAI genes expressed at the early phase of the cycle can be
      helpful in the design of potent adenovirus vectors.

PMID- 9188609
TI  - Human immunodeficiency virus type 1 preintegration complexes: studies of
      organization and composition.
AB  - We have investigated the organization and function of human immunodeficiency
      virus type 1 (HIV-1) preintegration complexes (PICs), the large nucleoprotein
      particles that carry out cDNA integration in vivo. PICs can be isolated from HIV
      1-infected cells, and such particles are capable of carrying out integration
      reactions in vitro. We find that although the PICs are large, the cDNA must be
      condensed to fit into the measured volume. The ends of the cDNA are probably
      linked by a protein bridge, since coordinated joining of the two ends is not
      disrupted by cleaving the cDNA internally with a restriction enzyme. cDNA ends in
      PICs were protected from digestion by added exonucleases, probably due to binding
      of proteins. The intervening cDNA, in contrast, was susceptible to attack by
      endonucleases. Previous work has established that the virus-encoded integrase
      protein is present in PICs, and we have reported recently that the host protein
      HMG I(Y) is also present. Here we report that the viral matrix and reverse
      transcriptase (RT) proteins also cofractionated with PICs through several steps
      whereas capsid and nucleocapsid proteins dissociated. These data support a model
      of PIC organization in which the cDNA is condensed in a partially disassembled
      remnant of the viral core, with proteins tightly associated at the apposed cDNA
      ends but loosely associated with the intervening cDNA. In characterizing the
      structure of the cDNA ends, we found that the U5 DNA ends created by RT were
      ragged, probably due to the terminal transferase activity of RT. Only molecules
      correctly cleaved by integrase protein at the 3' ends were competent to
      integrate, suggesting that one role for terminal cleavage by integrase may be to
      create a defined end at otherwise heterogeneous cDNA termini.

PMID- 9188610
TI  - Characterization of a novel third member of the human cytomegalovirus
      glycoprotein H-glycoprotein L complex.
AB  - A prerequisite for understanding the molecular function of the human
      cytomegalovirus (HCMV) gH (UL75)-gL (UL115) complex is a detailed knowledge of
      the structure of this complex in its functional form, as it is present in mature
      virions. The gH protein is known to be a component of a 240-kDa envelope complex
      designated as gCIII (D. R. Gretch, B. Kari, L. Rasmussen, R. C. Gehrz, and M. F.
      Stinski, J. Virol. 62:875-881, 1988). However, the exact composition of the gCIII
      complex remains unknown. In this report, we attempted reconstitution of the gCIII
      complex by coexpression of gH and gL in the baculovirus expression system.
      Formation of recombinant gH-gL complexes of approximately 115 kDa was
      demonstrated; however, no higher-molecular-mass (approximately 240-kDa)
      recombinant gH-gL complexes were detected, suggesting that the presence of gH and
      gL alone is not sufficient for reconstitution of the gCIII complex. To identify
      other mammalian and/or HCMV factors which may be necessary for gCIII formation,
      immunoprecipitates of gH and gL from HCMV-infected fibroblasts and purified HCMV
      virions were examined. This analysis did reveal a number of coprecipitating
      proteins which associate either transiently or integrally with gH and gL. One
      coprecipitating protein of 145 kDa was shown to be an integral component of
      gCIII, along with gH and gL. Characterization of the 145-kDa protein demonstrates
      that it is structurally and antigenically unrelated to gH and gL and that it
      appears to be virally encoded. Together, these data indicate that the 145-kDa
      protein is a third novel component of the mature HCMV gH-gL complex.

PMID- 9188611
TI  - Transcription of hepatitis B virus in peripheral blood mononuclear cells from
      persistently infected patients.
AB  - Hepatitis B virus (HBV) has been reported to exist in peripheral blood
      mononuclear cells (PBMC), but it is not clear whether it replicates there. A
      precondition for replication should be the formation of covalently closed viral
      DNA and transcription of all essential viral mRNAs. The mRNAs of HBV form a
      nested box with common 3' ends. In order to detect even low levels of potential
      replication, we developed a quantitative reverse transcription-PCR method for
      detection of a smaller HBV mRNA species in the presence of the larger ones. All
      three highly viremic patients tested so far had mRNAs for the large and the small
      surface proteins and the X protein of the virus within PBMC but not in the virus
      from their sera. Furthermore, we detected by PCR covalently closed viral DNA in
      their PBMC. These data suggest that HBV may be not only taken up but also
      replicated by mononuclear blood cells and that these cells may be an extrahepatic
      site of viral persistence. X mRNA was detected in the largest amount. Possibly, X
      protein interferes with functions of the mononuclear cells during the immune
      response against the virus.

PMID- 9188612
TI  - Effects of nucleotide changes on the ability of hepatitis delta virus to
      transcribe, process, and accumulate unit-length, circular RNA.
AB  - The circular RNA genome of hepatitis delta virus (HDV) can fold into an
      unbranched rodlike structure. We mutagenized the two ends of this structure and
      assayed the effects on the ability of the genomes to replicate and accumulate
      processed RNA transcripts in transfected cells. The top end, defined as that
      nearest to the 5' end of the putative mRNA for delta antigen, was much more
      sensitive than the other end, defined as the bottom. Most of the 22 mutants made
      at the bottom were able to accumulate RNA as well as the wild type. For deletions
      extending as close as 2 nucleotides (nt) from the predicted domains needed for
      the two ribozymes, the accumulation levels dropped to <0.1%. In one mutant, 13 nt
      of HDV was replaced with 57 nt of non-HDV sequences, and accumulation was at 20%
      of the wild-type level, consistent with the potential of HDV to act as a vector.
      However, after replacement with a second sequence, accumulation dropped to 1%.
      For most of the 14 mutants made at the top of the rod, we observed dramatic
      inhibitory effects. For example, after removal of 3 bp from the stem adjacent to
      the terminal loop, accumulation dropped to <0.06% of the wild-type genome level.
      The top region that we considered was adjacent to both the 5' end of the putative
      mRNA and the domain that has been proposed to contain a promoter for RNA-directed
      RNA synthesis. The RNA accumulation abilities of certain mutants were tested
      under additional different experimental conditions. It was found that after
      longer times, some mutants began to catch up with the wild type. Also, it was
      found that certain top mutants gave much greater levels of accumulation when
      transfected into cells containing the small delta antigen. One interpretation of
      these data is that certain features at the top of the rod are needed for the
      accumulation of essential delta antigen mRNA species.

PMID- 9188613
TI  - Serine protease of pestiviruses: determination of cleavage sites.
AB  - The single-stranded genomic RNA of pestiviruses is of positive polarity and
      encompasses one large open reading frame of about 4,000 codons. The resulting
      polyprotein is processed co- and posttranslationally by virus-encoded and host
      cell proteases to give rise to the mature viral proteins. A serine protease
      residing in the nonstructural (NS) protein NS3 (p80) has been shown to be
      essential for the release of the NS proteins located downstream of NS3. In this
      report the NS3 serine protease-dependent cleavage sites for bovine viral diarrhea
      virus (BVDV) strain CP7 are described. Proteins used for analysis were generated
      in Escherichia coli or in eukaryotic cells by the use of the T7 vaccinia virus
      system. The N termini of NS4A, NS4B, NS5A, and NS5B were determined by protein
      sequencing. Analysis of the data obtained showed that leucine at P1 is the only
      position conserved for all cleavage sites. At P1' alanine is found at the NS4A
      NS4B site, whereas serine resides at this position at the NS3-NS4A, NS4B-NS5A,
      and NS5A-NS5B cleavage sites. For all cleavage sites the amino acids found at P1
      and P1' are conserved for different genotypes of pestiviruses, despite the high
      degree of sequence variation found between these viruses. It is therefore assumed
      that the cleavage sites determined for BVDV CP7 are representative of those for
      all pestiviruses.

PMID- 9188614
TI  - Comprehensive quantification of herpes simplex virus latency at the single-cell
      level.
AB  - To date, characterization of latently infected tissue with respect to the number
      of cells in the tissue harboring the viral genome and the number of viral genomes
      contained within individual latently infected cells has not been possible. This
      level of cellular quantification is a critical step in determining (i) viral or
      host cell factors which function in the establishment and maintenance of latency,
      (ii) the relationship between latency burden and reactivation, and (iii) the
      effectiveness of vaccines or antivirals in reducing or preventing the
      establishment of latent infections. Presented here is a novel approach for the
      quantitative analysis of nucleic acids within the individual cells comprising
      complex solid tissues. One unique feature is that the analysis reflects the
      nucleic acids within the individual cells as they were in the context of the
      intact tissue-hence the name CXA, for contextual analysis. Trigeminal ganglia
      latently infected with herpes simplex virus (HSV) were analyzed by CXA of viral
      DNA. Both the type and the number of cells harboring the viral genome as well as
      the number of viral genomes within the individual latently infected cells were
      determined. Here it is demonstrated that (i) the long-term repository of HSV-1
      DNA in the ganglion is the neuron, (ii) the viral-genome copy number within
      individual latently infected neurons is variable, ranging over 3 orders of
      magnitude from <10 to >1,000, (iii) there is a direct correlation between
      increasing viral input titer and the number of neurons in which latency is
      established in the ganglion, (iv) increasing viral input titer results in more
      neurons with greater numbers of viral-genome copies, (v) treatment with acyclovir
      (ACV) during acute infection reduces the number of latently infected ganglionic
      neurons 20-fold, and (vi) ACV treatment results in uniformly low (<10)-copy
      number latency. This report represents the first comprehensive quantification of
      HSV latency at the level of single cells. Beyond viral latency, CXA has the
      potential to advance many studies in which rare cellular events occur in the
      background of a complex solid tissue mass, including microbial pathogenesis,
      tumorigenesis, and analysis of gene transfer.

PMID- 9188615
TI  - The herpes simplex virus type 1 latency-associated transcript gene regulates the
      establishment of latency.
AB  - Herpes simplex virus type 1 establishes latent infections in sensory neurons.
      During latency only one locus, the latency-associated transcript (LAT), is
      abundantly transcribed. Several lines of evidence suggest that this locus is
      required for the efficient reactivation from latency in experimental models.
      However, it is not yet clear whether this is a direct effect on the reactivation
      process per se or, as we have suggested, an indirect effect resulting from a
      decreased efficiency of establishment of latent infections. In this report wild
      type and genetically engineered viral mutants were analyzed in a mouse model
      using a recently developed approach to precisely quantify latently infected
      neurons. It was found that strain KOS/M established latent infections, as defined
      by the presence of the viral genome, in about 30% of the neurons. Thirty-three
      percent of the mice with this latent viral burden reactivated in vivo following
      hyperthermic stress. In contrast, mutants in which either the basal LAT promoter
      or the 5' end of the LAT gene was deleted established latency in only 10% of
      trigeminal neurons (P < 0.00001), and these mice were impaired for reactivation.
      Repair of the locus resulted in wild-type levels of establishment and
      reactivation, mapping this function to the LAT region. Finer mapping demonstrated
      that a 2.3-kb fragment that contains the major LAT transcripts was sufficient to
      promote efficient establishment and subsequent reactivation when expressed in the
      context of a foreign gene. Hyperthermic stress applied during the first 3 days
      postinfection resulted in greatly increased numbers of neurons harboring the
      latent viral genome. This approach was found to increase the level of
      establishment of LAT-null mutants to that normally achieved by wild-type KOS/M.
      These establishment-repaired mice reactivated with wild-type efficiency. Thus,
      the LAT gene serves to increase the number of neurons in which latency is
      established, and no direct role for the LAT locus in reactivation could be
      demonstrated.

PMID- 9188616
TI  - Sequence and drug susceptibility of subtype C reverse transcriptase from human
      immunodeficiency virus type 1 seroconverters in Zimbabwe.
AB  - Naturally occurring human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) variability has implications for the success of antiretroviral
      therapy. We determined the sequence of the polymerase-coding region of RT from
      virus isolates from 12 Zimbabwean individuals recently infected with HIV-1. The
      12 RT sequences differed from the consensus B RT sequence at 10.5% of nucleotides
      and 5.8% of amino acids. Susceptibility testing of five isolates to zidovudine,
      didanosine, lamivudine, and nevirapine demonstrated susceptibilities similar to
      those of wild-type subtype B isolates. Phylogenetic analysis of 40 HIV-1 RT
      sequences, including the 12 Zimbabwean subtype C sequences, 11 subtype B
      sequences, and the 17 remaining published non-subtype B sequences showed
      sufficient intrasubtype RT sequence variation to differentiate subtype A, B, C,
      and D isolates. Five recently reported subtype C RT sequences from India grouped
      with the Zimbabwean subtype C sequences but had significantly less intraisolate
      sequence variation. Both intra- and intersubtype RT comparisons were notable for
      extraordinarily high ratios of synonymous to nonsynonymous differences. Although
      substitutions in the HIV-1 RT gene are limited by functional constraints,
      variation between RT sequences demonstrates phylogenetic relationships that
      parallel env and gag gene variation.

PMID- 9188617
TI  - The small envelope protein is required for secretion of a naturally occurring
      hepatitis B virus mutant with pre-S1 deleted.
AB  - Naturally occurring deletions in the hepatitis B virus pre-S1 domain have been
      frequently found during persistent viral infection. In this study we have
      investigated the functional properties of a mutant viral genome that carries an
      in-frame deletion of 183 nucleotides in the pre-S1 region. This deletion removes
      the promoter of the small envelope gene. Transfection into human hepatocellular
      carcinoma cells of a replication-competent construct containing this deletion
      resulted in an increase of intermediate DNA replicative forms compared to those
      produced by wild-type hepatitis B virus. Northern blot analysis revealed that
      such cells lack the 2.1-kb transcripts encoding the small envelope protein and
      that hepatitis B surface antigen was absent as well. Furthermore, nucleocapsids
      containing the genome with pre-S1 deleted were not secreted, and the deleted
      large envelope protein was retained with the cytoplasm and exhibited a
      perinuclear pattern of distribution. However, coexpression with the small
      envelope protein was sufficient to restore virion secretion and to change the
      cellular distribution of the deleted large envelope protein. In addition, the
      creation of point mutations that prevent the synthesis of large or small envelope
      proteins also inhibited viral secretion and led to increased levels of hepatitis
      B virus intermediate replicative forms within the cell. These studies suggest
      that naturally occurring viral mutants with pre-S1 deletions involving the
      promoter region of the small envelope gene will generate a deleted large envelope
      protein that is retained in the endoplasmic reticulum, resulting in the
      accumulation of nucleocapsids containing viral DNA; transcomplementation with the
      wild-type small envelope protein will allow mutant virion secretion to occur.

PMID- 9188618
TI  - Increase in the frequency of hepadnavirus DNA integrations by oxidative DNA
      damage and inhibition of DNA repair.
AB  - Persistent hepadnavirus infection leads to oxidative stress and DNA damage
      through increased production of toxic oxygen radicals. In addition, hepadnaviral
      DNA integrations into chromosomal DNA can promote the process of
      hepatocarcinogenesis (M. Feitelson, Clin. Microbiol. Rev. 5:275-301, 1992). While
      previous studies have identified preferred integration sites in hepadnaviral
      genomes and suggested integration mechanisms (M. A. Buendia, Adv. Cancer Res.
      59:167-226, 1992; C. E. Rogler, Curr. Top. Microbiol. Immunol. 168:103-141, 1991;
      C. Shih et al., J. Virol. 61:3491-3498, 1987), very little is known about the
      effects of agents which damage chromosomal DNA on the frequency of hepadnaviral
      DNA integrations. Using a recently developed subcloning approach to detect stable
      new integrations of duck hepatitis B virus (DHBV) (S. S. Gong, A. D. Jensen, and
      C. E. Rogler, J. Virol. 70:2000-2007, 1996), we tested the effects of increased
      chromosomal DNA damage induced by H2O2, or of the disturbance in DNA repair due
      to the inhibition of poly(ADP-ribose) polymerase (PARP), on the frequency of DHBV
      DNA integrations. Subclones of LMH-D21-6 cells, which replicate DHBV, were grown
      in the presence of various H2O2 concentrations and exhibited up to a threefold
      increase in viral DNA integration frequency in a dose-dependent manner. Moreover,
      inhibition of PARP, which plays a role in cellular responses to DNA breakage, by
      3-aminobenzamide (3-AB) resulted in a sevenfold increase in the total number of
      new DHBV DNA integrations into host chromosomal DNA. Removal of either H2O2 or 3
      AB from the culture medium in a subsequent cycle of subcloning was accompanied by
      a reversion back towards the original lower frequency of stable DHBV DNA
      integrations for LMH-D21-6 cells. These data support the hypothesis that DNA
      damage sites can serve as sites for hepadnaviral DNA integration, and that
      increasing the number of DNA damage sites dramatically increases viral
      integration frequency.

PMID- 9188619
TI  - Complete nucleotide sequence of the new simian T-lymphotropic virus, STLV-PH969
      from a Hamadryas baboon, and unusual features of its long terminal repeat.
AB  - A third type of primate T-lymphotropic virus, PTLV-L, with STLV-PH969 as a
      prototype, has recently been isolated from an African baboon (Papio hamadryas).
      Classification of this virus has been based on partial sequence analysis of cDNA
      from a virus-producing cell line, PH969. We obtained the complete nucleotide
      sequence of this virus with a proviral genome of 8,916 bp. All major genes,
      homologous in all human T-cell lymphotropic virus (HTLV)-related viruses, and
      their corresponding mRNAs, including appropriate splicing, were identified. One
      additional nonhomologous open reading frame in the proximal pX region is
      accessible for translation through alternative splicing. Sequence comparison
      shows that STLV-PH969 is equidistantly related to HTLV type 1 (HTLV-1) and HTLV
      2. In all coding regions, the similarity tends to be the lowest between STLV
      PH969 and HTLV-1. However, in the long terminal repeat (LTR) region, the lowest
      similarity was found between STLV-PH969 and HTLV-2. The U3-R and R-U5 boundaries
      of the STLV-PH969 LTR were experimentally determined at nucleotides 268 and 524,
      respectively. This 695-bp LTR is 60 and 73 bp shorter than the LTRs of HTLV-1 and
      HTLV-2, respectively, but its general organization is similar to the one found in
      the HTLV-bovine leukemia virus genus. In the long region between the
      polyadenylation signal and the poly(A) site, sequence similarity with the HTLV-1
      Rex-responsive element (RexRE) core and secondary structure prediction suggest
      the presence of a RexRE. The presence of three 21-bp repeats is conserved within
      the U3 region of HTLV-1, HTLV-2, and BLV. Only two direct repeats with similarity
      to these Tax-responsive elements were found in the STLV-PH969 LTR, which might
      suggest differences in the Tax-mediated transactivation of this virus. We
      conclude that STLV-PH969 has all the genes and genomic regions to suggest a
      replication cycle comparable to that of HTLV-1 and HTLV-2.

PMID- 9188620
TI  - Immunogenicity of a contiguous T-B synthetic epitope of the A/PR/8/34 influenza
      virus.
AB  - A contiguously linked T-B synthetic viral epitope (110HA120-150HA159,T-B) was
      investigated for its potency in inducing humoral and cellular immune responses in
      vivo. The T-cell epitope 110HA120 corresponds to the site 1 hemagglutinin (HA) of
      the A/PR/8/34 (PR8) influenza virus and is recognized by CD4 T cells in
      association with I-Ed class II major histocompatibility complex molecules. The
      150HA159 represents a major B-cell epitope of the HA protein. T-B dipeptide
      emulsified in Freund's complete adjuvant was able to induce strong antiviral
      antibody titers and a high frequency of specific T-cell precursors after a single
      inoculation in BALB/c mice. In contrast, immunization under identical conditions
      with equimolar mixtures of T and B peptides did not elicit antibody titers or a
      cellular immune response. As indicated by the isotypes of antiviral antibodies,
      the T-B dipeptide preferentially induced a Th1-like immune response. Challenge
      with T-B dipeptide, but not with T or B peptide alone, stimulated peptide
      specific T memory cells in mice previously primed with PR8 virus or with T-B
      dipeptide. As a consequence, 71 and 57% of these mice, respectively, survived
      infection with two 100% lethal doses of PR8 virus. Our results suggest that,
      inasmuch as contiguity between T- and B-cell epitopes provides enough signaling
      capacity to trigger the mechanisms of T-B-cell cooperation in vivo, a T-B
      contiguous epitope may well represent a minimal built-in subunit vaccine. Aside
      from their potential bioavailability, the T-B contiguous epitopes may also
      represent attractive tools for investigating the molecular mechanisms of T-B-cell
      cooperation responsible for antiviral protection.

PMID- 9188621
TI  - Sendai virus efficiently infects cells via the asialoglycoprotein receptor and
      requires the presence of cleaved F0 precursor proteins for this alternative route
      of cell entry.
AB  - Biochemical evidence suggests that the asialoglycoprotein receptor (ASGP-R) can
      be used as an alternative receptor for a temperature-sensitive Sendai virus (SV)
      mutant. We now have investigated this possible alternative route of infection for
      SV wild-type (SV-wt) strain Fushimi by using a pair of cell lines which differ
      only with regard to ASGP-R expression. Infection studies after enzymatic
      destruction of conventional sialic acid-containing SV receptors (SA-R) revealed
      that only ASGP-R-expressing cells could be infected by SV-wt. This alternative
      route of cell entry could be completely blocked by incubation of cells with ASGP
      R-specific antibodies prior to infection. Furthermore, cleavage of SV-F0
      precursor protein into the subunits F1 and F2 was necessary to establish
      infection via ASGP-R, suggesting a fusion-mediated cell entry after binding of SV
      wt to the ASGP-R on host cells. Interestingly, infection via ASGP-R was found to
      be nearly as efficient as infection via conventional sialic acid-containing SV
      receptors. A possible physiological role of the ASGP-R-mediated route of SV
      infection is discussed.

PMID- 9188622
TI  - Formation of intracellular particles by hepatitis B virus large surface protein.
AB  - Hepatitis B virus small surface protein is synthesized as a transmembrane protein
      of the rough endoplasmic reticulum (RER) and then buds into the lumen in the form
      of subviral particles that are secreted. The closely related large surface
      protein is also targeted to the RER but is retained in a pre-Golgi compartment
      and cannot be secreted. It has been assumed that the large surface protein
      remains as a transmembrane RER protein and hence cannot form particles, possibly
      because of binding to a host factor on the cytosolic face of the RER membranes.
      We have reexamined this question and found the following results. (i) The
      retained large surface protein is associated not with RER but, rather, with a
      more distal compartment. (ii) Electron microscopy reveals intravesicular 20-nm
      particles, similar to those formed by the small surface protein. (iii) The large
      surface protein colocalizes with and binds to calnexin, an ER chaperone protein.
      Therefore, our results indicate that the large surface protein is capable of
      budding and forming particles, and hence its intracellular retention cannot be
      attributed to a cytosolic factor. We interpret the data as evidence that the
      large surface protein is retained by virtue of interacting with calnexin, a
      component of what is considered the quality control mechanism of the ER.

PMID- 9188623
TI  - The kappaB sites in the human immunodeficiency virus type 1 long terminal repeat
      enhance virus replication yet are not absolutely required for viral growth.
AB  - The dependence of human immunodeficiency virus type 1 (HIV-1) on its NF-kappaB
      binding sites (kappaB sites) for replication in transformed and primary T-cell
      targets was examined by infecting cells with HIV-1 reporter viruses containing
      kappaB site enhancer mutations. Viral transcription was measured either with
      luciferase-expressing HIV-1 that infects for a single round or by flow cytometric
      analyses with HIV-1 expressing placental alkaline phosphatase (PLAP) or green
      fluorescent protein (GFP). Both PLAP- and GFP-expressing viruses spread from cell
      to cell and allowed analysis of viral gene expression patterns in single cells.
      Infection of a panel of T-cell lines with different basal levels of NF-kappaB
      demonstrated a direct correlation between the amount of constitutive nuclear NF
      kappaB and the degree to which a wild-type virus outperformed kappaB site
      mutants. One T-cell line with a constitutively high level of nuclear NF-kappaB,
      PM1, showed a 20-fold decrease in transcription when its kappaB sites were
      mutated. In contrast, in a T-cell line with a low basal level of NF-kappaB,
      SupT1, mutation of the kappaB site in the enhancer had no effect on viral
      transcription or growth rate. Phytohemagglutinin-activated peripheral blood
      mononuclear cells showed a large dependence on the kappaB sites for optimal virus
      growth. Viruses without marker genes corroborated the finding that mutations to
      the kappaB sites impair virus production in cells with a high basal level of NF
      kappaB. These data show that in T cells, HIV-1 can use NF-kappaB to enhance its
      growth but the virus is clearly able to grow in its absence.

PMID- 9188624
TI  - Molecular analysis of the feline immunodeficiency virus protease: generation of a
      novel form of the protease by autoproteolysis and construction of cleavage
      resistant proteases.
AB  - The feline immunodeficiency virus (FIV) protease is essential for virion
      maturation and subsequent viral replication in that it cleaves the Gag and
      Gag/Pol polyproteins at eight sites to release the respective structural proteins
      and enzymes. During purification of a recombinant FIV protease (PR), we noted
      that it underwent autoproteolysis (autolysis) to give discrete cleavage products.
      These additional PR cleavage sites were defined using N-terminal amino acid
      sequence analysis and mass spectrometry. Protease breakdown products were also
      found in FIV virions and were of the same apparent molecular weights as the in
      vitro autolysis products. Four primary PR autolysis sites were blocked via
      substitution of either the P1 amino acid with a beta-branched amino acid or the
      P1' amino acid with lysine. Cleavage-resistant PRs which had Km and k(cat) values
      similar to those of FIV PR were constructed. An autolysis time course determined
      that blocking all four primary autolysis sites yielded a cleavage-resistant PR
      which was enzymatically stable. Concomitant with autolysis is the generation of
      an N-terminally truncated form of the PR (Thr6/PR) which has enhanced stability
      with respect to that of FIV PR. A structural basis for the Thr6/PR activity is
      presented, as are the possible roles of autolysis in the viral replication cycle.

PMID- 9188625
TI  - pp60c-src binding to polyomavirus middle T-antigen (MT) requires residues 185 to
      210 of the MT sequence.
AB  - Interaction with the src family of tyrosine kinases is crucial to the
      transforming action of polyomavirus middle T-antigen (MT). Association with MT
      activates the tyrosine kinase activity of pp60(c-src) and, through subsequent MT
      phosphorylation, creates binding sites for signalling molecules whose stimulation
      culminates in cell transformation. Despite this importance, and many studies,
      little is known of the mechanisms by which pp60(c-src) binds to MT. We report
      here isolation of the first MT mutants that disrupt pp60(c-src) binding without
      affecting the interaction between MT and protein phosphatase 2A (PP2A). Through
      deletion analysis we established that interaction with pp60(c-src) requires the
      sequences between amino acids 185 and 210 of MT, but these residues have no
      effect on PP2A binding. Cells expressing these mutants showed few altered
      properties, indicating that the PP2A-MT interaction alone has little influence on
      cell phenotype. Subcellular location of these mutant MT molecules was
      indistinguishable by immunofluorescence analysis from that of wild-type MT but
      was altered markedly on loss of PP2A binding. This suggests a possible role for
      PP2A in specifying subcellular distribution.

PMID- 9188626
TI  - Inhibition of human immunodeficiency virus replication by the herpes simplex
      virus virion host shutoff protein.
AB  - The herpes simplex virus (HSV) virion host shutoff gene (vhs) encodes a protein
      which nonspecifically accelerates the degradation of mRNA molecules, leading to
      inhibition of protein synthesis. This ability to inhibit a critical cellular
      function suggested that vhs could be used as a suicide gene in certain gene
      therapy applications. To investigate whether vhs might be useful for treatment of
      AIDS, we tested the ability of both HSV type 1 (HSV-1) and HSV-2 vhs to inhibit
      replication of human immunodeficiency virus (HIV). Replication of HIV was
      substantially inhibited when an infectious HIV proviral clone was cotransfected
      into HeLa cells together with vhs under the control of the cytomegalovirus (CMV)
      immediate-early promoter. HSV-2 vhs was more active than HSV-1 vhs in these
      experiments, consistent with previously published studies on these genes. Since
      expression of vhs from the CMV promoter is essentially unregulated, we also
      tested the ability of vhs expressed from the HIV long terminal repeat (LTR)
      promoter to inhibit HIV replication. Wild-type HSV-1 vhs inhibited HIV
      replication more than 44,000-fold in comparison to a mutant vhs gene encoding a
      nonfunctional form of the Vhs protein. Production of Vhs in transfected cells was
      verified by Western blot assays. A larger amount of Vhs was observed in cells
      transfected with plasmids expressing vhs from the HIV LTR than from the CMV
      promoter, consistent with the greater inhibition of HIV replication observed with
      these constructs. Mutant forms of Vhs were expressed at higher levels than wild
      type Vhs, most likely due to the ability of wild-type Vhs to degrade its own
      mRNA. The strong inhibitory activity of the vhs gene and its unique biological
      properties make vhs an interesting candidate for use as a suicide gene for HIV
      gene therapy.

PMID- 9188628
TI  - Regression of papillomas induced by cottontail rabbit papillomavirus is
      associated with infiltration of CD8+ cells and persistence of viral DNA after
      regression.
AB  - Cottontail rabbit papillomavirus (CRPV) is a highly oncogenic papillomavirus and
      has been successfully used as a model to develop protective vaccines against
      papillomaviruses. Papillomas induced by the virus may spontaneously regress,
      suggesting that CRPV can also serve as a model to develop therapeutic vaccines.
      As a first step toward this goal, we have analyzed immunologic and viral aspects
      associated with papilloma regression and have identified several features unique
      to regression. Immunohistochemical staining of biopsies from growing and
      regressing papillomas and from sites after complete regression showed
      infiltration of CD8+ cells into the basal and suprabasal layers of the epidermis
      only during active regression. In situ hybridizations with mRNA-specific probes
      were strongly positive for E6 and E7 mRNAs during regression, but no late mRNA
      was present. Viral DNA was detected by in situ hybridization during regression
      but not after regression. However, analysis by PCR revealed persistence of viral
      DNA for several months at the majority of regression sites. The results suggest
      that stimulation of a strong CD8+ response to virus-infected cells is important
      for an effective therapeutic vaccine and that special attention should be given
      to the suppression of latent infection.

PMID- 9188627
TI  - Recognition of prominent viral epitopes induced by immunization with human
      immunodeficiency virus type 1 regulatory genes.
AB  - Mice immunized with the regulatory genes nef, rev, and tat from human
      immunodeficiency virus type 1 developed both humoral and cellular immune
      responses to the gene products Nef, Rev, and Tat. This study demonstrates that it
      is feasible to induce immune reactions to all of these regulatory gene products.
      Humoral responses were seen after DNA boosts, while potent T-cell proliferative
      responses were noted already after a single immunization. A Th1-directed immune
      response was demonstrated early after immunization. A 3- to 75-fold-stronger T
      cell response was seen in animals receiving DNA epidermally compared to that in
      animals receiving intramuscular injections. Nef, Rev, and Tat putative B- and T
      cell epitopes were clearly mapped by using peptides derived from the regulatory
      proteins and were similar to those which are detected in human immunodeficiency
      virus infection. Although immunization by the Nef, Rev, and Tat proteins raised
      high immunoglobulin G titers in serum, the epitope spreading appeared broader
      after DNA immunization. The combination of all of these regulatory genes together
      with two genes for structural proteins, the envelope and gag genes, demonstrated
      that a combined approach is feasible in that reactivities to all antigens
      persisted or were even augmented. No interference between plasmids was noted.

PMID- 9188629
TI  - Mutagenesis analysis of the murine leukemia virus matrix protein: identification
      of regions important for membrane localization and intracellular transport.
AB  - We have created two sets of substitution mutations in the Moloney murine leukemia
      virus (Mo-MuLV) matrix protein in order to identify domains involved in
      association with the plasma membrane and in incorporation of the viral envelope
      glycoproteins into virus particles. The first set of mutations was targeted at
      putative membrane-associating regions similar to those of the human
      immunodeficiency virus type 1 matrix protein, which include a polybasic region at
      the N terminus of the Mo-MuLV matrix protein and two regions predicted to form
      beta strands. The second set of mutations was created within hydrophobic residues
      to test for the production of virus particles lacking envelope proteins, with the
      speculation of an involvement of the membrane-spanning region of the envelope
      protein in incorporation into virus particles. We have found that mutation of the
      N-terminal polybasic region redirected virus assembly to the cytoplasm, and we
      show that tryptophan residues may also play a significant role in the
      intracellular transport of the matrix protein. In total, 21 mutants of the Mo
      MuLV matrix protein were produced, but we did not observe any mutant virus
      particles lacking the envelope glycoproteins, suggesting that a direct
      interaction between the Mo-MuLV matrix protein and envelope proteins either may
      not exist or may occur through multiple redundant interactions.

PMID- 9188630
TI  - The range and distribution of murine central nervous system cells infected with
      the gamma(1)34.5- mutant of herpes simplex virus 1.
AB  - Wild-type herpes simplex virus 1 (HSV-1) multiplies, spreads, and rapidly
      destroys cells of the murine central nervous system (CNS). In contrast, mutants
      lacking both copies of the gamma(1)34.5- gene have been shown to be virtually
      lacking in virulence even after direct inoculation of high-titered virus into the
      CNS of susceptible mice (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman,
      Science 250:1262-1266, 1990). To investigate the host range and distribution of
      infected cells in the CNS of mice, 4- to 5-week-old mice were inoculated
      stereotaxically into the caudate/putamen with 3 x 10(5) PFU of the gamma(1)34.5-
      virus R3616. Four-micrometer-thick sections of mouse brains removed on day 3, 5,
      or 7 after infection were reacted with a polyclonal antibody directed primarily
      to structural proteins of the virus and with antibodies specific for neurons,
      astrocytes, or oligodendrocytes. This report shows the following: (i) most of the
      tissue damage caused by R3616 was at the site of injection, (ii) the virus spread
      by retrograde transport from the site of infection to neuronal cell nuclei at
      distant sites and to ependymal cells by cerebrospinal fluid, (iii) the virus
      infected neurons, astrocytes, oligodendrocytes, and ependymal cells and hence did
      not discriminate among CNS cells, (iv) viral replication in some neurons could be
      deduced from the observation of infected astrocytes and oligodendrocytes at
      distant sites, and (v) infected cells were being efficiently cleared from the
      nervous system by day 7 after infection. We conclude that the gamma(1)34.5-
      attenuation phenotype is reflected in a gross reduction in the ability of the
      virus to replicate and spread from cell to cell and is not due to a restricted
      host range. The block in viral replication appears to be a late event in viral
      replication.

PMID- 9188631
TI  - Initiation of DNA synthesis by human papillomavirus E7 oncoproteins is resistant
      to p21-mediated inhibition of cyclin E-cdk2 activity.
AB  - The E6 and E7 proteins from the high-risk human papillomaviruses (HPVs) bind and
      inactivate the tumor suppressor proteins p53 and Rb, respectively. In HPV
      positive cells, expression of E6 proteins from high-risk types results in
      increased turnover of p53, which leads to an abrogation of p21-mediated G1/S
      arrest in response to DNA-damaging agents. In contrast, keratinocytes which
      express E7 alone have increased levels of p53 but, interestingly, also fail to
      undergo a G1/S arrest. We investigated the mechanism by which E7 bypasses this
      p21 arrest by using both keratinocytes which stably express E7 as well as U20S
      cells which stably or transiently express E7. We observed that E7 does not affect
      the induction of p21 synthesis by p53. While glutathione S-transferase (GST)-E7
      bound a low level of in vitro-translated p21, we were unable to detect E7 and p21
      in the same complex by GST-E7 binding assays or immunoprecipitations from cell
      extracts. Furthermore, E7 did not prevent p21-mediated inhibition of cyclin E
      kinase activity. In keratinocytes expressing E7, increased levels of p53, p21,
      and cyclin E, as well as increased cyclin E kinase activity, were observed. To
      determine if this increase in cyclin E activity was necessary for E7's ability to
      overcome p21-mediated G1/S arrest, we examined U20S cells in which cyclin E
      levels are not increased in response to E7 expression. U20S cells which stably
      express E7 were found to initiate DNA synthesis in the presence of DNA-damaging
      agents despite the inhibition of cyclin E activity by p21. In transient assays,
      cotransfection of E7 or E2F-1 along with p21 into U20S cells rescued G1 arrest
      and resulted in S-phase entry, as measured by the ability to incorporate
      bromodeoxyuridine. These data indicate that E7 is able to overcome G1/S arrest
      without directly affecting p21 function and likely acts through deregulation of
      E2F activity.

PMID- 9188632
TI  - Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle
      arrest.
AB  - The human immunodeficiency virus type 1 (HIV-1) vpr gene encodes a protein which
      induces arrest of cells in the G2 phase of the cell cycle. Here, we demonstrate
      that following the arrest of cells in G2, Vpr induces apoptosis in human
      fibroblasts, T cells, and primary peripheral blood lymphocytes. Analysis of
      various mutations in the vpr gene revealed that the extent of Vpr-induced G2
      arrest correlated with the levels of apoptosis. However, the alleviation of Vpr
      induced G2 arrest by treatment with the drug pentoxifylline did not abrogate
      apoptosis. Together these studies indicate that induction of G2 arrest, but not
      necessarily continued arrest in G2, was required for Vpr-induced apoptosis to
      occur. Finally, Vpr-induced G2 arrest has previously been correlated with
      inactivation of the Cdc2 kinase. Some models of apoptosis have demonstrated a
      requirement for active Cdc2 kinase for apoptosis to occur. Here we show that
      accumulation of the hypophosphorylated or active form of the Cdc2 kinase is not
      required for Vpr-induced apoptosis. These studies indicate that Vpr is capable of
      inducing apoptosis, and we propose that both the initial arrest of cells and
      subsequent apoptosis may contribute to CD4 cell depletion in HIV-1 disease.

PMID- 9188633
TI  - Vpr of simian immunodeficiency virus of African green monkeys is required for
      replication in macaque macrophages and lymphocytes.
AB  - The genomes of simian immunodeficiency viruses isolated from African green
      monkeys (SIVagm) contain a single accessory gene homolog of human
      immunodeficiency virus type 1 (HIV-1) vpr. This genomic organization differs from
      that of SIVsm-SIVmac-HIV-2 group viruses, which contain two gene homologs,
      designated vpr and vpx, which in combination appear to share the functions of HIV
      1 vpr. The in vitro role of the SIVagm homolog was evaluated with molecularly
      cloned, pathogenic SIVagm9063-2. These studies revealed that this gene shares
      properties of HIV-1 vpr, such as nuclear and virion localization. In addition,
      SIVagm mutants with inactivating mutations of vpr are unable to replicate in
      nondividing cells, such as macaque monocyte-derived macrophages, but replicate to
      almost wild-type levels in a susceptible human T-cell line. The transport of
      virus preintegration complexes into the nucleus in primary macrophages, as
      measured by the production of unintegrated circular viral DNA, is less efficient
      for the mutant viruses than it is for the wild-type virus. SIVagm mutants also
      replicate inefficiently in primary macaque peripheral blood mononuclear cells,
      with a propensity for substitutions that remove the inserted inactivating stop
      codon. These data, in conjunction with recent findings that the Vpr protein is
      capable of inducing G2 arrest, are consistent with designation of this SIVagm
      accessory gene as vpr to reflect its shared functions and properties with HIV-1
      vpr.

PMID- 9188634
TI  - Apoptosis plays an important role in experimental rabies virus infection.
AB  - Cultured rat prostatic adenocarcinoma (AT3) cells infected with the challenge
      virus standard (CVS) strain of fixed rabies virus showed characteristic
      morphologic features of apoptosis, evidence of oligonucleosomal DNA
      fragmentation, and expression of the Bax protein. CVS-infected Bcl-2-transfected
      AT3 cells did not demonstrate these features. Adult ICR mice inoculated
      intracerebrally with CVS showed morphologic changes of apoptosis, DNA
      fragmentation, and increased Bax expression in neurons, with changes most marked
      in the hippocampus and cerebral cortex. Ultrastructurally, some neurons
      demonstrated morphologic features more typical of necrosis. These studies provide
      evidence that apoptosis plays an important role in the pathogenesis of rabies
      virus infection.

PMID- 9188635
TI  - Genotypic and phenotypic characterization of long terminal repeat sequences from
      long-term survivors of human immunodeficiency virus type 1 infection.
AB  - Human immunodeficiency virus type 1 (HIV-1)-infected individuals who remain
      asymptomatic despite prolonged infection present a unique opportunity to
      understand virologic and immunologic factors involved in the pathogenesis of
      AIDS. We have previously identified a group of long-term survivors (LTS) who are
      clinically healthy and immunologically normal despite 13 to 15 years of HIV-1
      infection. In this study, we examined the 5' long terminal repeat (5' LTR)
      sequences in eight of these LTS. A total of 29 nucleotide sequences were obtained
      from their peripheral blood mononuclear cells (PBMC). Analysis of these sequences
      revealed no gross deletions within the 5' LTR. Seven of the eight subjects shared
      nearly identical consensus sequences in the binding sites for NF-kappaB, Sp1, and
      the viral trans-activator Tat. In multiple samples from one individual (Pt 5),
      however, G-to-A hypermutations were found throughout the entire region,
      suggesting a genetically defective 5' LTR. The effects of the observed genetic
      variations on LTR transcription were studied by transient transfection of an LTR
      driven luciferase reporter gene and by infection with a full-length recombinant
      HIV-1 containing a luciferase reporter (HIVHXBLTRluc). A wide range of basal and
      Tat-induced transcriptional activities was found among the 5' LTR from seven of
      the eight LTS in both transfected 293 cells and donor PBMC, suggesting a
      functionally intact 5' LTR in these individuals. It is therefore unlikely that
      defects in the 5' LTR are the underlying explanation for the benign clinical
      course associated with these seven individuals. However, functional abnormalities
      were found in the LTR from Pt 5 in directing both heterologous and viral gene
      expression, providing a possible genetic explanation for the low viral load and
      prolonged asymptomatic state of this individual. Last, a similar overall degree
      of genetic diversity was found among viruses from the LTS compared to those from
      patients with AIDS, reinforcing the notion that a strong correlation between the
      degree of genetic diversity and the rate of disease progression is unlikely.

PMID- 9188636
TI  - Evidence for translation of the Borna disease virus G protein by leaky ribosomal
      scanning and ribosomal reinitiation.
AB  - The Borna disease virus antigenome includes five major open reading frames (ORFs)
      which encode, from 5' to 3', the putative nucleoprotein (N), the phosphoprotein
      (P), the putative matrix protein (M), the major glycoprotein (G), and the RNA
      dependent RNA polymerase (pol). Whereas the N and P ORFs are translated from
      monocistronic transcripts, the M, G, and pol ORFs are translated from
      polycistronic transcripts. Expression of the M, G, and pol ORFs is dependent upon
      differential splicing of two introns (intron 1, 94 nucleotides [nt]; intron 2,
      1,294 nt). In vitro transcription-translation assays of wild-type and mutant
      sequences indicated that the G ORF is translated from an unspliced 2.8-kb RNA by
      leaky ribosomal scanning. Splicing of intron 1 enhances the translation of the G
      ORF by converting the M ORF into a 13-amino-acid minicistron, a structure that
      facilitates ribosomal reinitiation.

PMID- 9188637
TI  - Simian virus 40 T antigen can regulate p53-mediated transcription independent of
      binding p53.
AB  - A simian virus 40 (SV40) T-antigen mutant containing only the N-terminal 136
      amino acids, able to bind to Rb and p300 but not p53, partially inhibited p53
      mediated transcription without affecting the ability of p53 to bind DNA. These
      results suggest that SV40 T antigen can regulate p53-mediated transcription
      either directly through protein-protein association or indirectly through
      interaction with factors which may function to confer p53-mediated transcription.

PMID- 9188638
TI  - Genetic analysis of interactions between Gag proteins of Rous sarcoma virus.
AB  - The yeast two-hybrid system was used to characterize homomeric interactions
      between the Gag proteins of Rous sarcoma virus (RSV). The RSV Gag precursor was
      found to interact strongly with itself and not with various control proteins. The
      RSV Gag did not interact significantly with Gag proteins of a variety of other
      retroviruses, including murine leukemia viruses and primate lentiviruses.
      Deletion analysis suggested that two nonoverlapping regions are independently
      sufficient to mediate RSV Gag-Gag dimerization. One such region lies near the N
      terminus and contains p2, p10, and a large N-terminal part of the capsid (CA)
      domain; the other is localized in the C terminus and includes a small C-terminal
      portion of CA and the nucleocapsid protein. These interaction domains may play
      roles in viral assembly.

PMID- 9188639
TI  - Identification of an ATPase activity associated with a 71-kilodalton polypeptide
      encoded in gene 1 of the human coronavirus 229E.
AB  - Human coronavirus 229E gene expression involves proteolytic processing of the
      gene 1-encoded polyproteins pp1a and pp1ab. In this study, we have detected a 71
      kDa polypeptide in virus-infected cells that is released from pp1ab by the virus
      encoded 3C-like proteinase and that has been predicted to contain both metal
      binding and helicase domains. The polypeptide encompasses amino acids Ala-4996 to
      Gln-5592 of pp1ab and exhibits nucleic acid-stimulated ATPase activity when
      expressed as a fusion protein with the Escherichia coli maltose-binding protein.
      These data provide the first identification of a coronavirus open reading frame
      1b-encoded enzymatic activity.

PMID- 9188640
TI  - The pseudorabies virus UL51 gene product is a 30-kilodalton virion component.
AB  - Positional homologs to the UL51 open reading frame of herpes simplex virus type 1
      have been identified throughout the herpesvirus family. However, no respective
      protein has so far been described for any of the herpesviruses. With rabbit
      antisera directed against oligopeptides predicted to comprise antigenic regions
      of the deduced pseudorabies virus (PrV) UL51 protein, a polypeptide with a size
      of 30 kDa was identified in PrV-infected cell lysates and in purified virions.
      This molecular mass correlates reasonably well with the predicted mass of 25 kDa
      of the 236-amino-acid deduced UL51 protein. Antisera raised against peptides
      derived from different predicted antigenic regions all detected the 30-kDa
      protein in Western blot (immunoblot) analyses. Specificity was ascertained by
      peptide competition. Subcellular fractionation showed the presence of the UL51
      protein mainly in the nucleus of infected cells. After separation of purified
      virion preparations into envelope and capsid, the PrV UL51 protein was detected
      in the capsid fraction. In summary, we identified the first herpesvirus UL51
      protein and demonstrate that it represents a structural component of PrV virions.

PMID- 9188641
TI  - The UL20 gene product of pseudorabies virus functions in virus egress.
AB  - The UL20 open reading frame is positionally conserved in different
      alphaherpesvirus genomes and is predicted to encode an integral membrane protein.
      A previously described UL20- mutant of herpes simplex virus type 1 (HSV-1)
      exhibited a defect in egress correlating with retention of virions in the
      perinuclear space (J. D. Baines, P. L. Ward, G. Campadelli-Fiume, and B. Roizman,
      J. Virol. 65:6414-6424, 1991). To analyze UL20 function in a related but
      different herpesvirus, we constructed a UL20- pseudorabies virus (PrV) mutant by
      insertional mutagenesis. Similar to HSV-1, UL20- PrV was found to be severely
      impaired in both cell-to-cell spread and release from cultured cells. The
      severity of this defect appeared to be cell type dependent, being more prominent
      in Vero than in human 143TK- cells. Surprisingly, electron microscopy revealed
      the retention of enveloped virus particles in cytoplasmic vesicles of Vero cells
      infected with UL20- PrV. This contrasts with the situation in the UL20- HSV-1
      mutant, which accumulated virions in the perinuclear cisterna of Vero cells.
      Therefore, the UL20 gene products of PrV and HSV-1 appear to be involved in
      distinct steps of viral egress, acting in different intracellular compartments.
      This might be caused either by different functions of the UL20 proteins
      themselves or by generally different egress pathways of PrV and HSV-1 mediated by
      other viral gene products.

PMID- 9188642
TI  - VP5 of infectious bursal disease virus is not essential for viral replication in
      cell culture.
AB  - Infectious bursal disease virus (IBDV), a member of the Birnaviridae family,
      encodes in its bisegmented double-stranded RNA genome four structural virion
      proteins, VP1, VP2, VP3, and VP4, as well as a nonstructural protein, VP5.
      Recently, the establishment of an infectious cRNA system for IBDV has been
      described (E. Mundt and V. N. Vakharia, Proc. Natl. Acad. Sci. USA 93:11131
      11136, 1996). Here, we report the isolation of a VP5- IBDV mutant constructed by
      site-directed mutagenesis of the methionine start codon of VP5, followed by cRNA
      transfection. The resulting virus mutant was replication competent in cell
      culture, which indicates that VP5 is not required for productive replication of
      IBDV. Absence of VP5 expression was verified by lack of reactivity with newly
      established anti-VP5 monoclonal antibodies and polyclonal sera. VP5- IBDV
      exhibited a delay in replication in chicken embryo cells compared to the VP5+
      parental virus. However, final yields were similar. Our results thus show that
      VP5 is nonessential for IBDV replication, which makes it a prime candidate for
      the construction of deleted, marked vaccines.

PMID- 9188643
TI  - Cloning of a new murine endogenous retrovirus, MuERV-L, with strong similarity to
      the human HERV-L element and with a gag coding sequence closely related to the
      Fv1 restriction gene.
AB  - We had previously identified a new family of human endogenous retrovirus-like
      elements, the HERV-L elements (human endogenous retrovirus with leucine tRNA
      primer), whose pol gene was most closely related to that of the foamy viruses.
      HERV-L pol-related sequences were also detected in other mammalian species. The
      recent cloning of the mouse Fv1 gene (S. Best, P. Le Tissier, G. Towers, and J.
      P. Stoye, Nature 382:826-829, 1996) has shed light on another HERV-L domain-
      identified as a gag gene based on its location within the provirus--which was
      found to be 60% identical, at the nucleotide level, to the Fv1 open reading frame
      (ORF). We have now cloned the murine homolog of HERV-L which, in contrast to HERV
      L, displays fully open reading frames in the gag and pol genes. Its predicted Gag
      protein shares 43% identity with the Fv1 ORF product. Moreover, the
      characteristic major homology region of the capsid subdomain can be identified
      within both proteins, thus strongly emphasizing the gag-like origin of Fv1.

PMID- 9188644
TI  - Rhabdovirus-induced apoptosis in a fish cell line is inhibited by a human
      endogenous acid cysteine proteinase inhibitor.
AB  - To determine the mechanisms of cell death in rhabdovirus-infected cells, we
      studied the infection of the epithelial papilloma of carp cell line with spring
      viremia of carp virus. Studies using electron microscopy, confocal microscopy,
      and agarose gel electrophoresis revealed changes in cell morphology and DNA
      fragmentation indicative of apoptosis. The virus-induced apoptosis was inhibited
      in cells treated with a human endogenous acid cysteine proteinase inhibitor.

PMID- 9188646
TI  - Subunit-specific mutagenesis of the cysteine 280 residue of the reverse
      transcriptase of human immunodeficiency virus type 1: effects on sensitivity to a
      specific inhibitor of the RNase H activity.
AB  - Treatment of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT)
      with N-ethylmaleimide (NEM) selectively inhibits the RNase H activity. The
      cysteine residue at position 280 (C280) is the target for NEM; HIV-1 RT carrying
      the mutation C280S is resistant to NEM. Since HIV-1 RT is composed of two related
      subunits (p66 and p51) that play distinct roles, we asked whether the C280 in p51
      or the C280 in p66 is responsible for the sensitivity of the enzyme to NEM. HIV-1
      RT versions were prepared that had one mutant and one wild-type subunit. When
      these chimeric enzymes were tested, both the p51 and p66 subunits were found to
      contribute to the sensitivity of the enzyme to NEM. The implications of these
      results are discussed in the context of the structure of the enzyme.

PMID- 9188645
TI  - Adeno-associated virus type 2-mediated transfer of ecotropic retrovirus receptor
      cDNA allows ecotropic retroviral transduction of established and primary human
      cells.
AB  - The cellular receptors that mediate binding and internalization of retroviruses
      have recently been identified. The concentration and accessibility of these
      receptors are critical determinants in accomplishing successful gene transfer
      with retrovirus-based vectors. Murine retroviruses containing ecotropic
      glycoproteins do not infect human cells since human cells do not express the
      receptor that binds the ecotropic glycoproteins. To enable human cells to become
      permissive for ecotropic retrovirus-mediated gene transfer, we have developed a
      recombinant adeno-associated virus type 2 (AAV) vector containing ecotropic
      retroviral receptor (ecoR) cDNA under the control of the Rous sarcoma virus (RSV)
      long terminal repeat (LTR) promoter (vRSVp-ecoR). Established human cell lines,
      such as HeLa and KB, known to be nonpermissive for murine ecotropic retroviruses,
      became permissive for infection by a retroviral vector containing a bacterial
      gene for resistance to neomycin (RV-Neo(r)), with a transduction efficiency of up
      to 47%, following transduction with vRSVp-ecoR, as determined by the development
      of colonies that were resistant to the drug G418, a neomycin analog. No G418
      resistant colonies were present in cultures infected with either vRSVp-ecoR or RV
      Neo(r) alone. Southern and Northern blot analyses revealed stable integration and
      long-term expression, respectively, of the transduced murine ecoR gene in clonal
      isolates of HeLa and KB cells. Similarly, ecotropic retrovirus-mediated Neo(r)
      transduction of primary human CD34+ hematopoietic progenitor cells from normal
      bone marrow was also documented, but only following infection with vRSVp-ecoR.
      The retroviral transduction efficiency was approximately 7% without
      prestimulation and approximately 14% with prestimulation of CD34+ cells with
      cytokines, as determined by hematopoietic clonogenic assays. No G418-resistant
      progenitor cell colonies were present in cultures infected with either vRSVp-ecoR
      or RV-Neo(r) alone. These results suggest that sequential transduction of primary
      human cells with two different viral vectors may overcome limitations encountered
      with a single vector. Thus, the combined use of AAV- and retrovirus-based vectors
      may have important clinical implications for ex vivo and in vivo human gene
      therapy.

PMID- 9188647
TI  - Fish nodavirus lytic cycle and semipermissive expression in mammalian and fish
      cell cultures.
AB  - In this study, Dicentrarchus labrax encephalitis virus (DlEV), which causes sea
      bass encephalitis, was propagated in cell culture, thus allowing study of its
      lytic cycle. DlEV infection of mammalian and fish cells induced different
      patterns of expression of capsid proteins, which were assembled as virus-like
      particles, accumulating in the cytoplasm either as diffuse masses or in vesicles,
      as shown by electron microscopy. These particles correspond to virions, as shown
      by their ability to induce secondary infection. Fish cells proved to be more
      permissive for DlEV than mammalian cells, although virus yield remained low. RNA
      analysis of infected sea bass cells revealed DlEV RNA3, in addition to genomic
      RNA1 and RNA2, and the presence of the RNA2 minus strand, thus demonstrating the
      replication of the DlEV genome. In addition, DlEV RNA-dependent RNA polymerase
      was associated with mature virions even after purification by a CsCl gradient,
      but it was dissociated when capsids were destabilized. In addition to providing
      more information about the relatedness of DlEV to the members of the family
      Nodaviridae, this study shows that fish nodaviruses may not be able to infect as
      wide a variety of cells as insect nodaviruses can.

PMID- 9188648
TI  - A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the
      dual-tropic human immunodeficiency virus type 1 isolate HIV-1(89.6) but not the T
      tropic isolate HIV-1(HxB).
AB  - We used a monoclonal antibody (12G5) directed against an extracellular domain of
      CXCR-4 to investigate the role of this receptor in infection of immortalized
      lymphoid cell lines, peripheral blood mononuclear cells (PBMCs), and primary
      brain microglia with a dual-tropic strain of human immunodeficiency virus (HIV
      1(89.6)) and a T-tropic strain (HIV-1(IIIB)). Addition of antibody 12G5 to cells
      prior to and during infection with HIV-1(89.6) inhibited p24 production 100- to
      10,000-fold in CEMx174 and 174-CD4 cells and about 10-fold in PBMC cultures but
      had no activity against infection of either monocyte-derived macrophages or brain
      microglia. In contrast, 12G5 had little or no effect on infection of CEMx174
      cells with HIV-1(IIIB) or HIV-1(HxB). To identify the region of the HIV-1(89.6)
      envelope that confers sensitivity to 12G5, we used chimeric molecular clones.
      Chimeras containing the V3 loop region of HIV-1(89.6) were inhibited by 12G5 to
      the same degree as wild-type HIV-1(89.6) whereas replication of those viruses
      containing the V3 loop of HIV-1(HxB) was not inhibited by the antibody. A similar
      pattern was seen in infections of a U87 glioblastoma line that coexpresses CD4
      and CXCR-4. Antibody 12G5 was also able to block fusion between HeLa-CD4 cells
      and CEMx174 cells chronically infected with HIV-1(89.6) but had no effect on
      fusion mediated by cells chronically infected with HIV-1(IIIB). Taken together,
      these results suggest that different strains of HIV-1 may interact with different
      sites on CXCR-4 or may have different binding affinities for the coreceptor.

PMID- 9188649
TI  - A subgenomic mRNA transcript of the coronavirus mouse hepatitis virus strain A59
      defective interfering (DI) RNA is packaged when it contains the DI packaging
      signal.
AB  - In infected cells, only the genomic RNA of the coronavirus mouse hepatitis virus
      strain A59 (MHV-A59) is packaged into the virions. In this study, we show that a
      subgenomic (sg) defective interfering (DI) RNA can be packaged into virions when
      it contains the DI RNA packaging signal (DI RNA-Ps). However, the sg DI RNA is
      packaged less efficiently than the DI genomic RNA. Thus, while specificity of
      packaging of RNAs into MHV-A59 virions is determined by the DI RNA-Ps, efficiency
      of packaging is determined by additional factors.

PMID- 9188650
TI  - Epstein-Barr virus infection of human gastric carcinoma cells: implication of the
      existence of a new virus receptor different from CD21.
AB  - Recombinant Epstein-Barr virus (EBV) with a selectable marker successfully
      infected the human gastric carcinoma cell lines AGS, MKN28, and MKN74. Following
      incubation in selective media, drug-resistant cell clones were isolated and
      proved to be infected with EBV. All gastric carcinoma cell clones were positive
      for EBNA 1 but negative for EBNA 2. LMP 1 expression was negative in most clones,
      but there were a few exceptions. Gastric carcinoma cells were negative for the
      EBV receptor CD21, and infection was not inhibited by pretreatment of cells with
      the anti-CD21 monoclonal antibody OKB7. The results indicate that gastric
      carcinoma cells are susceptible to EBV infection and that infection is mediated
      via a new receptor different from CD21.

PMID- 9188651
TI  - Human cytomegalovirus induces interleukin-8 production by a human monocytic cell
      line, THP-1, through acting concurrently on AP-1- and NF-kappaB-binding sites of
      the interleukin-8 gene.
AB  - Cytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription
      in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion. The
      functional analysis of the IL-8 gene revealed that both AP-1- and NF-kappaB
      factor-binding elements were involved in conferring the responsiveness to CMV.
      Moreover, electrophoretic mobility shift assays demonstrated that CMV induced the
      formation of NF-kappaB and AP-1 complexes. These results suggest that CMV
      activates these transcriptional factors, resulting in IL-8 gene expression.

PMID- 9188653
TI  - pIRS1 and pTRS1 are present in human cytomegalovirus virions.
AB  - The virus-coded proteins pIRS1 and pTRS1 were found associated with purified
      human cytomegalovirus virions. The proteins were not degraded when intact virions
      were treated with trypsin, which suggests that they are localized inside the
      viral particle. In transfection experiments pIRS1 and pTRS1 modestly activated
      expression from a reporter plasmid containing the viral major immediate-early
      promoter but did not influence the activity of a reporter carrying the irs1/trs1
      immediate-early promoter. Both reporters were activated by the combination of
      pIRS1 or pTRS1 and pUL69, which is also present in virions.

PMID- 9188652
TI  - Two distinct oncornaviruses harbor an intracytoplasmic tyrosine-based basolateral
      targeting signal in their viral envelope glycoprotein.
AB  - It has been clearly established that the budding of the human immunodeficiency
      virus (HIV-1), a lentivirus, occurs specifically through the basolateral membrane
      in polarized epithelial cells. More recently, the signal was assigned to a
      tyrosine-based motif located in the intracytoplasmic domain of the envelope
      glycoprotein, as previously observed on various other viral and cellular
      basolateral proteins. In the present study, expression of human T-cell leukemia
      virus type 1 (HTLV-1) or Moloney murine leukemia virus envelope glycoproteins was
      used for trans-complementation of an envelope-negative HIV-1. This demonstrated
      the potential of oncornaviral retrovirus envelope glycoproteins to confer
      polarized basolateral budding in epithelial Madin-Darby canine kidney cells (MDCK
      cells). Site-directed mutagenesis confirmed the importance of a common motif
      encompassing at least one crucial membrane-proximal intracytoplasmic tyrosine
      residue. The conservation of a similar basolateral maturation signal in different
      retroviruses further supports its importance in the biology of this group of
      viruses.

PMID- 9188654
TI  - Human immunodeficiency virus type 1 and 2 envelope glycoproteins oligomerize
      through conserved sequences.
AB  - Hetero-oligomerization between human immunodeficiency virus type 2 (HIV-2)
      envelope glycoprotein (Env) truncation mutants and epitope-tagged gp160 is
      dependent on the presence of gp41 transmembrane protein (TM) amino acids 552 to
      589, a putative amphipathic alpha-helical sequence. HIV-2 Env truncation mutants
      containing this sequence were also able to form cross-type hetero-oligomers with
      HIV-1 Env. HIV-2/HIV-1 hetero-oligomerization was, however, more sensitive to
      disruption by mutagenesis or increased temperature. The conservation of the Env
      oligomerization function of the HIV-1 and HIV-2 alpha-helical sequences suggests
      that retroviral TM alpha-helical motifs may have a universal role in
      oligomerization.

PMID- 9188655
TI  - Ectodermal dysplasia, cleft lip/palate, and severe cutaneous and osseous
      syndactyly in a mentally retarded girl: a new multiple malformation syndrome.
AB  - A 13-year-old mentally retarded girl with severe cutaneous and osseous syndactyly
      of the hands and feet, cleft lip/palate, and ectodermal dysplasia is presented.
      We conclude that the pattern of malformations described represents a new multiple
      malformation syndrome. A comparison with Zlotogora-Ogur syndrome is presented.

PMID- 9188656
TI  - Patient with an Xp21 contiguous gene deletion syndrome in association with
      agenesis of the corpus callosum.
AB  - The so-called Xp21 contiguous deletion syndrome or complex glycerol kinase
      deficiency (GKD) usually presents with classical Duchenne muscular dystrophy
      (DMD) or a milder dystrophic myopathy, adrenal hypoplasia, and GKD. A number of
      syndromic and nonsyndromic cases of agenesis of the corpus callosum (ACC) also
      map to that location. To date, none of the cases of complex GKD have been
      associated with ACC. Here, we report on a patient with a complex phenotype as a
      result of the Xp21 contiguous deletion syndrome in association with ACC.
      Biochemical, cytogenetic, and molecular analyses were performed to detect and
      establish the size of the genomic deletion. It is at least 3 million base pairs
      in length; however, exact limits could not be determined in the present study.
      Nevertheless, we suggest the presence of a primary gene involved in the
      embryogenesis of the corpus callosum between Xp21.1 and Xp22.11.

PMID- 9188657
TI  - Familial translocation t(Y;15)(q12;p11) and de novo deletion of the Prader-Willi
      syndrome (PWS) critical region on 15q11-q13.
AB  - We describe a 17-year-old girl with mild Prader-Willi syndrome (PWS) due to 15q11
      q13 deletion. The deletion occurred on a paternal chromosome 15 already involved
      in a translocation, t(Y;15)(q12;p11), the latter being present in five other,
      phenotypically normal individuals in three generations. This appears to be the
      first case of PWS in which the causative 15q11-q13 deletion occurred on a
      chromosome involved in a familial translocation, but with breakpoints
      considerably distal to those of the familial rearrangement. The translocation
      could predispose to additional rearrangements occurring during meiosis and/or
      mitosis or, alternatively, the association of two cytogenetic anomalies on the
      same chromosome could be fortuitous.

PMID- 9188658
TI  - Lateral meningocele syndrome: three new patients and review of the literature.
AB  - One female and two male patients with multiple lateral meningoceles are
      presented. They do not have neurofibromatosis or Marfan syndrome and share
      findings with the two previously described patients with multiple lateral
      meningoceles. The original report by Lehman et al. [1977: J Pediatr 90:49-54] was
      titled "familial osteosclerosis," because osteosclerosis was present in the
      proposita and her mother; the patient described by Philip et al. [1995: Clin
      Dysmorphol 4:347-351] also had increased bone density of the skull base and the
      sutures. Thickened calvaria were present in one of our patients; two had a
      prominent metopic suture. Other shared findings include multiple lateral
      meningoceles, Wormian bones, malar hypoplasia, downslanted palpebral fissures, a
      high narrow palate, and cryptorchidism in males. In addition, our patients showed
      ligamentous laxity, keloid formation, hypotonia, and developmental delay. A short
      umbilical cord was noted in two patients. One had a hypoplastic posterior arch of
      the atlas and an enlarged sella, as reported by Lehman et al. [1977]. Our
      patients appear to have the same syndrome as previously reported. We suggest it
      be called "lateral meningocele syndrome," because of this unique finding.

PMID- 9188659
TI  - Pattern of deletions of the dystrophin gene in Mexican Duchenne/Becker muscular
      dystrophy patients: the use of new designed primers for the analysis of the major
      deletion "hot spot" region.
AB  - We have analyzed 59 unrelated Mexican Duchenne/Becker muscular dystrophy patients
      (DMD/BMD) using PCR analysis of the 2 prone deletion regions in the DMD gene.
      Thirty one (52%) of the patients had a deletion of one or several of the exons.
      Most of the alterations (87%) were clustered in exons 44-52, this being the
      highest percentage reported until now. In order to improve the molecular
      diagnosis in the Mexican population, we designed a new multiplex assay to PCR
      amplify exons 44-52. This assay allowed for the identification of a greater
      number of deletions in this region compared with the 9 and 5-plex assays
      previously described and to determine most of the deletion end boundaries. This
      is a reliable alternative for the initial screening of the DMD patients in the
      Mexican population.

PMID- 9188660
TI  - New autosomal recessive syndrome of progressive sensorineural hearing loss and
      cataracts: report on two Brazilian patients.
AB  - We report on two sisters with cataracts and progressive sensorineural hearing
      loss, starting in infancy. They were born to consanguineous parents, and there
      were no similar cases in the family. To our knowledge this is the first report on
      this autosomal recessive condition. Clinical and genetic aspects are discussed.

PMID- 9188661
TI  - Urorectal septal defects in a female and her offspring.
AB  - We report on a patient with an ectopic urethra opening into a septate vagina
      which was distended with urine. The anus and rectum were normal but separated
      from the urogenital sinus by a thin septum. After surgical repair the patient did
      well with the exception of recurrent urinary tract infections. At 16 years, she
      delivered a healthy boy by Cesarean section but miscarried a subsequent pregnancy
      3 years later. The 12-13 week female fetus lacked a urethra and had an atretic
      vagina and cloacal anomalies consistent with a urorectal septum developmental
      defect. This report provides evidence that cloacal anomalies resulting from the
      improper development of the urorectal septum may have a genetic cause.
      Furthermore, we support the proposition previously set forth by Allen and Husmann
      [J Urol 145:1034-1039, 1991] that such anomalies be referred to as urorectal
      septal defects rather than cloacal anomaly variants. This terminology accurately
      represents the developmental defect and clearly distinguishes them from cloacal
      exstrophies, which are due to the abnormal development of the cloacal membrane
      and the subumbilical ventral abdominal wall.

PMID- 9188662
TI  - Unexpected familial recurrence in Angelman syndrome.
AB  - We report on two instances of familial recurrence of Angelman syndrome which,
      from pedigree analysis, appear incompatible with currently known mechanisms of
      inheritance of this disorder. In these two families, deletion-positive Angelman
      syndrome has recurred in cousins. Several established mechanisms for deletion
      positive familial recurrence have been ruled out. In each family, molecular
      cytogenetic studies show typical chromosome 15 deletions, and DNA methylation
      analysis verifies the maternal origin of the deleted chromosomes in all four
      individuals. Since the mothers of the affected individuals in each family are not
      known to be related, these recurrences appear to be secondary to coincidental, de
      novo events. This conclusion is consistent with direct and indirect estimates of
      the population frequency of Angelman syndrome.

PMID- 9188664
TI  - Extended survival in a new case of ter Haar syndrome: further delineation of the
      syndrome.
AB  - We present a boy followed from age 5-13 years who is the fifth reported case of
      ter Haar syndrome. This is a recently-named entity comprising congenital
      glaucoma, hypertelorism, congenital heart defects and kyphoscoliosis, skeletal
      dysplasia, and developmental delay. These patients were originally thought to
      have an autosomal-recessive form of Melnick-Needles syndrome, and were only
      identified as having a distinct syndrome with the report of the fourth case.
      Probable autosomal-recessive inheritance is based on consanguinity in 4 of 5
      cases. Ocular, cardiac, and craniofacial findings distinguish ter Haar syndrome
      as a distinct entity. Our patient is the longest survivor at present, suggesting
      that there is heterogeneity in this syndrome or, alternatively, that aggressive
      therapy of the congenital heart defects has significant effect.

PMID- 9188663
TI  - Severe Hajdu-Cheney syndrome with upper airway obstruction.
AB  - Hajdu-Cheney syndrome is an autosomal dominant disorder of acroosteolysis, skull
      deformities, characteristic facial abnormalities, osteoporosis, joint laxity,
      early loss of teeth, hearing loss, and a hoarse voice. We report on an 8 1/2-year
      old boy with Hajdu-Cheney syndrome and cystic kidney disease, congenital heart
      disease, hydrocephalus, cleft lip and palate, hydrosyringomyelia, club feet,
      splenomegaly, hypospadias, vertebral anomalies, and upper airway obstruction. A
      review of 44 patients did not uncover any other patients with all of these
      manifestations, nor any patient with upper airway obstruction. Hajdu-Cheney
      syndrome appears to encompass a broader phenotype than previously recognized. The
      documentation of these additional anomalies is valuable because the findings of
      acroosteolysis and osteoporosis can present later in the course.

PMID- 9188665
TI  - Early complete hydatidiform moles contain inner cell mass derivatives.
AB  - In four cases of early complete hydatidiform moles, confirmed to be androgenetic
      in origin by DNA studies, we have identified nonchorionic inner cell mass derived
      structures which are not commonly observed in specimens of later gestational age.
      These structures include nucleated red blood cells, endothelial cells, stromal
      macrophages, amnion and yolk sac. The latter four structures were confirmed by
      specific immunocytochemical stains. Recognition that such structures can
      accompany complete hydatidiform moles has both theoretical and practical
      significance. From a theoretical perspective, it demonstrates that the maternal
      genome is not required for the initiation of amniogenesis, development of the
      yolk sac, vasculogenesis, or hematopoiesis. From a practical perspective it
      emphasizes that complete hydatidiform moles, with their markedly increased risk
      of subsequent choriocarcinoma, cannot be excluded based on the finding of "fetal
      structures."

PMID- 9188666
TI  - Identification of supernumerary der(20) chromosomes by FISH in three patients.
AB  - Small supernumerary marker chromosomes of 3 patients were characterized at the
      molecular cytogenetic level. Two ring chromosomes and one metacentric marker were
      shown to be distamycinA/DAPI-negative and did not possess satellite regions after
      conventional banding techniques. Fluorescence in situ hybridization (FISH) was
      performed and in all 3 cases the supernumerary markers were shown to be derived
      from chromosome 20. Phenotypes are described and discussed with respect to
      karyotypes. Two of the patients are developmentally and/or phenotypically normal.
      The first patient has a ring chromosome, containing a small amount of euchromatic
      material; the second patient is the carrier of a small, metacentric and most
      probably heterochromatic marker. Patient 3 has physical anomalies, including a
      congenital heart defect and delayed motor development, but is intellectually
      almost normal. His marker chromosome is a ring containing a small amount of
      euchromatic material.

PMID- 9188667
TI  - Intestinal malrotation in a child with cardio-facio-cutaneous syndrome.
AB  - We present a child with cardio-facio-cutaneous (CFC) syndrome with inadequate
      weight gain due to inadequate food intake. After correction of hyperemesis due to
      intestinal malrotation, she continued to fail to feed due to poor suck reflex. A
      review documented digestive system findings in 26 of 57 reported patients with
      CFC syndrome. Thus, digestive system dysfunction and malformation may represent
      an additional manifestation of the CFC syndrome.

PMID- 9188668
TI  - Mosaicism in pseudoachondroplasia.
AB  - Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia
      characterized by disproportionate short stature, generalized ligamentous laxity,
      and precocious osteoarthritis. PSACH is caused by mutations in the cartilage
      oligomeric matrix protein (COMP) gene, which codes for a noncollagenous protein
      expressed in the territorial matrix of chondrocytes. Autosomal dominant
      inheritance has been demonstrated in many families; however, autosomal recessive
      inheritance has been suggested in some severe familial cases. Alternatively,
      germline/somatic mosaicism has been proposed and is credible, since it has been
      shown that dominantly inherited and sporadic cases of PSACH are caused by the
      same genetic defect. Here, we present evidence demonstrating somatic mosaicism in
      two PSACH families that were originally considered to represent autosomal
      recessive inheritance. The results of this study suggest that autosomal recessive
      inheritance is unlikely and all cases of PSACH should be studied for mutations in
      COMP.

PMID- 9188669
TI  - Chromosome abnormalities in congenital heart disease.
AB  - Refinements in cytogenetic techniques have promoted progress in understanding the
      role that chromosome abnormalities play in the cause of congenital heart disease.
      To determine if mutations at specific loci cause congenital heart disease,
      irrespective of the presence of other defects, and to estimate the prevalence of
      chromosome abnormalities in selected conotruncal cardiac defects, we reviewed
      retrospectively cytogenetic and clinical databases at St. Louis Children's
      Hospital. Patients with known 7q11.23 deletion (Williams syndrome), Ullrich
      Turner syndrome (UTS), and most autosomal trisomies were excluded from this
      analysis. Two groups of patients were studied. Over a 6.5-year period, 57
      patients with chromosomal abnormalities and congenital heart disease were
      identified. Of these, 37 had 22q11 deletions; 5 had abnormalities of 8p; and 15
      had several other chromosome abnormalities. The prevalence of chromosome
      abnormalities in selected conotruncal or aortic arch defects was estimated by
      analysis of a subgroup of patients from a recent 22-month period. Chromosome
      abnormalities were present in 12% of patients with tetralogy of Fallot, 26% in
      tetralogy of Fallot/pulmonary atresia, 44% in interrupted aortic arch, 12% in
      truncus arteriosus, 5% in double outlet right ventricle, and 60% in absent
      pulmonary valve. We conclude that chromosome analysis should be considered in
      patients with certain cardiac defects. Specifically, fluorescent in situ
      hybridization (FISH) analysis of 22q11 is indicated in patients with conotruncal
      defects or interrupted aortic arch. High resolution analysis should include
      careful evaluation of the 8p region in patients with either conotruncal or
      endocardial cushion defects.

PMID- 9188670
TI  - Novel point mutation in the uroporphyrinogen III synthase gene causes congenital
      erythropoietic porphyria of a Japanese family.
AB  - The molecular basis of the uroporphyrinogen III synthase (UROIIIS) deficiency was
      investigated in a member of a Japanese family. This defect in heme biosynthesis
      is responsible for a rare autosomal recessive disease: congenital erythropoietic
      porphyria (CEP) or Gunther's disease. The patient was homozygous for a novel
      missense mutation: a G to T transition of nucleotide 7 that predicted a valine to
      phenylalanine substitution at residue 3 (V3F). The parents were heterozygous for
      the same mutation. The loss of UROIIIS activity was verified by an in vitro assay
      system. The corresponding mutated protein was expressed in Escherichia coli and
      no residual activity was observed. Further studies are needed to determine
      whether the mutations of the UROIIIS gene (UROS) have a specific profile in Japan
      compared to European or American countries.

PMID- 9188671
TI  - Strain-dependent alterations in the expression of folate pathway genes following
      teratogenic exposure to valproic acid in a mouse model.
AB  - The molecular basis for the well-established hierarchy of susceptibility to
      valproic acid-induced neural tube defects in inbred mouse strains was examined
      using in situ transcription and anti-sense RNA amplification methodologies with
      both univariate and multivariate analyses of the resulting gene expression data.
      The highly sensitive SWV strain demonstrated a significant reduction in the
      expression of the folate binding protein (FBP-1) following the teratogenic insult
      at gestational day 8:18, while the more resistant LM/Bc embryos were up
      regulating this gene in response to valproic acid treatment. More importantly, at
      all 3 gestational timepoints spanning the period of murine neural tube closure
      examined in this study, the LM/Bc embryos had significantly higher MTHFR (5,10
      methylenetetrahydrofolate reductase) gene expression levels compared to the SWV
      embryos. As this folate pathway enzyme is important in homocysteine and
      methionine metabolism, it suggests that the SWV embryos may be hypomethylated,
      and essential gene expression during critical periods of neural tube closure is
      compromised by the teratogenic exposure to valproic acid. This study represents
      the first evidence of a strain difference in transcriptional activity in response
      to a teratogenic exposure that might be causally related to the development of
      the teratogen-induced congenital malformations.

PMID- 9188672
TI  - Macrocephaly, facial abnormalities, disproportionate tall stature, and mental
      retardation--a sib observation.
AB  - We report on two brothers with relatively short limbs, macrocephaly, high and
      narrow forehead, frontal upsweep of hairline, hypotelorism, broad but short ears,
      straight back, and mild hypermobility of all joints. Both were hypotonic
      neonatally and had developmental delay and behavior problems. Several of the
      manifestations were present in the father, too. A literature search failed to
      uncover any similar case.

PMID- 9188673
TI  - Oto- spondylo-megaepiphyseal dysplasia (OSMED): clinical description of three
      patients homozygous for a missense mutation in the COL11A2 gene.
AB  - We describe a syndrome of midface hypoplasia, non-progressive sensorineural
      deafness and epiphyseal dysplasia in 3 sibs born to consanguineous parents.
      Clinical and roentgenographic findings are compatible with a diagnosis of oto
      spondylo-megaepiphyseal dysplasia (OSMED). Histologic study of cartilage shows
      severe osteoarthritis, which may necessitate joint replacements in early
      adulthood. Ultrastructurally, collagen fibrils are increased in diameter and show
      aggregation. These findings have not been reported previously and may be
      diagnostic of OSMED. The affected sibs are homozygous for a COL11A2 missense
      mutation. We compare the clinical findings in our patients with a group of
      patients who have a dominantly inherited, non-ocular form of Stickler syndrome
      due to a COL11A2 splice-site mutation. Both syndromes include midface hypoplasia,
      epiphyseal dysplasia, and deafness, more pronounced in OSMED. Since mutations
      affecting the collagen XI genes can obviously result in a spectrum of phenotypes,
      we performed a literature-search using POSSUM, OSSUM, and the LDDB to identify
      conditions that might also be caused by mutations in one of the collagen XI
      genes. A number of conditions matched the search terms in all databases. Of
      these, Marshall syndrome is very similar to OSMED. Considering these phenotypic
      similarities and the close association between the COL11A1 and COL11A2 gene
      products, we propose that Marshall syndrome may be caused by a mutation in
      COL11A1. We also identify a number of other conditions that could be caused by
      mutations in one of the collagen XI genes.

PMID- 9188674
TI  - Interstitial deletion of 2q associated with craniosynostosis, ocular coloboma,
      and limb abnormalities: cytogenetic and molecular investigation.
AB  - We report on the clinical and cytogenetic findings in a 9-year-old boy with a de
      novo deletion of 2q, shown by molecular analysis to have arisen from the paternal
      chromosome. Examination of microsatellite markers indicated deletion of bands
      2q24.3 and 2q31. Clinical findings included craniosynostosis, bilateral ocular
      colobomata, and limb abnormalities, the latter being an emerging association with
      deletion of this region of 2q.

PMID- 9188675
TI  - Genotype and phenotype in Angelman syndrome caused by paternal UPD 15.

PMID- 9188676
TI  - NTD phenotypes in infants and fetuses whose mothers used multivitamins containing
      folic acid in early pregnancy compared to those who did not.

PMID- 9188677
TI  - Toriello-Carey syndrome.

PMID- 9188678
TI  - Apparently new syndrome of congenital cataracts, sensorineural deafness, Down
      syndrome-like facial appearance, short stature, and mental retardation.

PMID- 9188679
TI  - Paired melanotic and achromic macules in a case of phacomatosis
      pigmentovascularis: a further example of twin spotting?

PMID- 9188680
TI  - A new pathway for transmembrane electron transfer in photosynthetic reaction
      centers of Rhodobacter sphaeroides not involving the excited special pair.
AB  - It is generally accepted that electron transfer in bacterial photosynthesis is
      driven by the first singlet excited state of a special pair of
      bacteriochlorophylls (P*). We have examined the first steps of electron transfer
      in a mutant of the Rhodobacter sphaeroides reaction center in which charge
      separation from P* is dramatically slowed down. The results provide for the first
      time clear evidence that excitation of the monomeric bacteriochlorophyll in the
      active branch of the reaction center (B(A)) drives ultrafast transmembrane
      electron transfer without the involvement of P*, demonstrating a new and
      efficient mechanism for solar energy transduction in photosynthesis. The most
      abundant charge-separated intermediate state probably is P+B(A)-, which is formed
      within 200 fs from B(A)* and decays with a lifetime of 6.5 ps into P+H(A)-. We
      also see evidence for the involvement of a B(A)+H(A)- state in the alternative
      pathway.

PMID- 9188681
TI  - S(-3) state of the water oxidase in photosystem II.
AB  - The effect of the reductant hydrazine on the flash-induced oxygen oscillation
      patterns of spinach thylakoids was used to characterize a new super-reduced redox
      state of the water oxidase in photosystem II. The formation of a discrete S(-3)
      state is evident from the shift of the first maximum of oxygen evolution from the
      3rd flash through the 5th flash to the 7th flash during a 90 min incubation of
      dark-adapted thylakoids with 10 mM hydrazine sulfate at pH 6.8 on ice. A distinct
      period four oscillation with further maxima on the 11th and 15th flashes is still
      observed at this stage of the incubation. The data analysis within the framework
      of an extended Kok model reveals that a S(-3) state population of almost 50% can
      be achieved by this treatment. A prolonged incubation of the S(-3) sample with 10
      mM hydrazine (and even 100 mM) does not lead to a further shift of the first
      maximum toward the 9th flash that could reflect the formation of the S(-5) state.
      Instead, a slow oxidation of S(-3) to S(-2) takes place by an as yet unidentified
      electron acceptor. A consistent simulation of all the measured oxygen oscillation
      patterns of this study could, however, only be achieved by including the formal
      redox states S(-4) and S(-5) in the fits (S(-4) + S(-5) up to 35%). The
      implications of these findings for the oxidation states of the manganese in the
      tetranuclear cluster of the water oxidase are discussed.

PMID- 9188682
TI  - Identification of a chameleon-like pH-sensitive segment within the colicin E1
      channel domain that may serve as the pH-activated trigger for membrane bilayer
      association.
AB  - In vitro, the channel-forming domain of colicin E1 requires activation by acidic
      pH (<4.5) or detergents. The activation of this domain to its insertion-competent
      state results in an increased ability of the protein to dock onto and to form
      channels in artificial membranes. Fluorescence methods were used to characterize
      the conformational changes occurring in a channel-forming peptide of colicin E1
      in solution with pH. The 178-residue thermolytic fragment of colicin E1 contains
      three Trp residues, W-424, W-460, and W-495. In order to study the structural and
      dynamic requirements for activation of the C-terminal domain of colicin E1,
      single-Trp-containing peptides were prepared by site-directed mutagenesis. All of
      the mutant peptides displayed in vitro channel activity and cellular cytotoxicity
      similar to the those of wild-type peptide. Two Trp residues, W-413 and W-424,
      exhibited pH-sensitive fluorescence parameters. Upon acidification (pH 6.0 -->
      3.5), the fluorescence quantum yield of W-413 and W-424 increased 50% and 80%,
      respectively, indicating a significant change in the local environment of the
      peptide segment containing these two Trp residues. The fluorescence decay of W
      413 and W-424 was best fit by three fluorescence decay components, two of which
      were sensitive to pH. However, only small changes in spectral shape and position
      were observed for W-424 fluorescence, whereas there were larger changes in these
      fluorescence parameters for W-413. The quantum yields for the Trp residues in the
      seven other single-Trp mutant peptides and the wild-type peptide were distinct
      but only slightly affected by changes in pH. Time-resolved fluorescence
      measurements showed that W-460, -484, and -495 each had two fluorescence decay
      components with similar decay times, with one component dominating the
      fluorescence decay behavior. Furthermore, the individual fluorescence decay times
      for all the single-Trp peptides, except for W-413 and W-424, were insensitive to
      pH changes. At pH 3.5, the fluorescence of the wild-type peptide was fit by three
      decay time components, with the two longer decay times being quite different from
      the fluorescence decay times of the single-Trp mutant proteins (W-424, -460, and 
      495, the naturally occurring Trp residues). In contrast, at pH 6.0, the wild-type
      peptide showed double-exponential decay kinetics. Time-resolved fluorescence
      anisotropy decay measurements of the three single-Trp mutant proteins, containing
      a naturally occurring Trp residue, suggest that local segmental motion of the
      peptide as reported by each of the three tryptophans is highly restricted and
      largely insensitive to changes in pH. On the other hand, the anisotropy decay
      profiles of the wild-type protein were consistent with energy transfer occurring
      between Trp residues, likely between W-460 and W-495. These steady-state and time
      resolved fluorescence results show that W-413 and W-424 report conformational
      changes which may be associated with the insertion-competent state and reside on
      the protein segment(s) which form the pH-activated trigger of the channel
      peptide.

PMID- 9188683
TI  - Structures of the reduced and mercury-bound forms of MerP, the periplasmic
      protein from the bacterial mercury detoxification system.
AB  - Bacteria carrying plasmids with the mer operon, which encodes the proteins
      responsible for the bacterial mercury detoxification system, have the ability to
      transport Hg(II) across the cell membrane into the cytoplasm where it is reduced
      to Hg(0). This is significant because metallic mercury is relatively nontoxic and
      volatile and thus can be passively eliminated. The structures of the reduced and
      mercury-bound forms of merP, the periplasmic protein, which binds Hg(II) and
      transfers it to the membrane transport protein merT, have been determined in
      aqueous solution by multidimensional NMR spectroscopy. The 72-residue merP
      protein has a betaalpha betabeta alphabeta fold with the two alpha helices
      overlaying a four-strand antiparallel beta sheet. Structural differences between
      the reduced and mercury-bound forms of merP are localized to the metal binding
      loop containing the consensus sequence GMTCXXC. The structure of the mercury
      bound form of merP shows that Hg(II) is bicoordinate with the Cys side chain
      ligands, and this is confirmed by the chemical shift frequency of the 199Hg
      resonance.

PMID- 9188684
TI  - Residue accessibility, hydrogen bonding, and molecular recognition: metal-chelate
      probing of active site histidines in chymotrypsins.
AB  - Subspecies defining the maturation pathway of bovine chymotrypsinogen to alpha
      chymotrypsin have been separated in a single chromatographic run by affinity to
      iminodiacetic acid-Cu(II) [IDA-Cu(II)] immobilized onto Novarose. A major
      highlight of the elution pattern is that, as maturation proceeds, these
      subspecies exhibit a correlated increase in affinity toward IDA-Cu(II). This
      behavior is analyzed by a combination of physicochemical and molecular modeling
      techniques to assess the contribution of the two histidines present in
      chymotrypsins, at positions 40 and 57 on the protein surface. Catalytic His-57
      features adequate surface accessibility to serve as a ligand to IDA-Cu(II), but
      its participation is clearly ruled out by specific chemical modification. In
      contrast, His-40, whose side chain is buried in the crystal structures of both
      zymogen and mature enzyme, surprisingly proves the most plausible candidate as an
      electron donor to IDA-Cu(II). This apparent conflict between histidine
      accessibility and their implication in IDA-Cu(II) recognition has been
      rationalized on the basis of their flexibility and/or hydrogen-bonding status,
      with the following outcome. First, histidine constitutes a useful reporter group
      for subtle protein conformational fluctuations. Second, static accessibility
      computation alone provides no unequivocal guideline as to whether a protein
      residue can serve as a ligand. Third, this study is the first to document the
      occurrence of a screening effect due to hydrogen bonding of an otherwise
      "accessible" histidine. A significant corollary to this finding would be that the
      catalytic histidine is rigidly entrapped in a remarkably strong hydrogen-bonding
      network, a situation that may pertain to mechanistic aspects of catalysis.

PMID- 9188685
TI  - Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin,
      conantokin G, from the marine snail Conus geographus: the metal-free conformer.
AB  - Conantokin G is a gamma-carboxyglutamic acid-containing conotoxin from the venom
      of the marine cone snail Conus geographus. The 17-residue peptide, which contains
      five gamma-carboxyglutamic acid (Gla) residues and an amidated C-terminal
      asparagine amide, was synthesized chemically in a form identical to the natural
      conantokin G. To gain insight into the role of gamma-carboxyglutamic acid in the
      structure of this peptide, we determined the three-dimensional structure of
      conantokin G by 1H NMR and compared its structure to other conotoxins and to the
      gamma-carboxyglutamic acid-containing regions of the vitamin K-dependent blood
      clotting proteins. Complete resonance assignments were made by two-dimensional 1H
      NMR spectroscopy in the absence of metal ions. NOE cross-peaks d(alphaN), d(NN),
      and d(betaN) provided interproton distance information, and vicinal spin-spin
      coupling constants 3J(HN alpha) were used to calculate phi torsion angles.
      Distance geometry and simulated annealing methods were used to derive 20
      convergent structures from a set of 227 interproton distance restraints and 13
      torsion angle measurements. The backbone rmsd to the geometric average for 20
      final structures is 0.8 +/- 0.1 A. Conantokin G consists of a structured region
      commencing at Gla 3 and extending through arginine 13. This structure includes a
      partial loop centered around Gla 3 and Gla 4, a distorted type I turn between
      glutamine 6 and glutamine 9, and two type I turns involving Gla 10, leucine 11,
      and isoleucine 12 and arginine 13. Together, these two turns define approximately
      1.6 turns of a distorted 3(10) helix. The observed structure possesses structural
      elements similar to those seen in the disulfide-linked conotoxins.

PMID- 9188687
TI  - Amino acid sequence environment modulates the disruption by osteogenesis
      imperfecta glycine substitutions in collagen-like peptides.
AB  - Ostoegenesis imperfecta (OI) or "brittle bone" disease is associated with
      mutations in the genes for type I collagen chains and produces variable
      phenotypes, ranging from lethal cases at birth to mild cases with increased bone
      fractures. The most common OI mutations are single base substitutions leading to
      replacement of Gly by another residue, breaking the typical (Gly-X-Y)n repeating
      sequence pattern of the collagen triple-helix. Triple-helical peptides were
      designed to focus on residues 892-921 of the alpha1 chain of type I collagen,
      where two OI Gly-->Ser mutations are found in close proximity, a mild mutation at
      site 901 and a lethal mutation at site 913. Peptides were designed to include
      amino acid sequences around these mutation sites, and were synthesized with the
      normal sequence or with the Gly-->Ser mutated sequence. The peptide including the
      normal sequence residues 892-909 with four Gly-Pro-Hyp triplets at the C-terminus
      formed a stable triple-helix, and introduction of a Ser residue for Gly at the
      901 mutation site led to a 50% loss of triple-helix content and a decrease in
      thermal stability, with little effect on folding. A peptide including residues
      904-921 again formed a stable triple-helix, but the introduction of the Gly-->Ser
      substitution at site 913 led to a much greater decrease in thermal stability.
      These studies demonstrate the impact of local sequences flanking the Gly
      substitution on structural consequences and support the concept of variability
      and regional effects along the collagen molecule.

PMID- 9188686
TI  - NMR structural analysis of an analog of an intermediate formed in the rate
      determining step of one pathway in the oxidative folding of bovine pancreatic
      ribonuclease A: automated analysis of 1H, 13C, and 15N resonance assignments for
      wild-type and [C65S, C72S] mutant forms.
AB  - A three-disulfide intermediate, des-[65-72] RNase A, lacking the disulfide bond
      between Cys65 and Cys72, is formed in one of the rate-determining steps of the
      oxidative regeneration pathways of bovine pancreatic ribonuclease A (RNase A). An
      analog of this intermediate, [C65S, C72S] RNase A, has been characterized in
      terms of structure and thermodynamic stability. Triple-resonance NMR data were
      analyzed using an automated assignment program, AUTOASSIGN. Nearly all backbone
      1H, 13C, and 15N resonances and most side-chain 13C(beta) resonances of both wild
      type (wt) and [C65S, C72S] RNase A were assigned unambiguously. Analysis of NOE,
      13C(alpha) chemical shift, and 3J(H(N)-H(alpha)) scalar coupling data indicates
      that the regular backbone structure of the major form of [C65S, C72S] RNase A is
      very similar to that of the major form of wt RNase A, although small structural
      differences are indicated in the mutation site and in spatially adjacent beta
      sheet structures comprising the hydrophobic core. Thermodynamic analysis
      demonstrates that [C65S, C72S] RNase A (Tm of 38.5 degrees C) is significantly
      less stable than wt RNase A (Tm of 55.5 degrees C) at pH 4.6. Although the
      structural comparison of wt RNase A and this analog of an oxidative folding
      intermediate indicates only localized effects around the Cys65 and Cys72 sites,
      these thermodynamic measurements indicate that formation of the fourth disulfide
      bond, Cys65-Cys72, on this oxidative folding pathway results in global
      stabilization of the native chain fold. This conclusion is supported by
      comparisons of amide 1H/2H exchange rates which are significantly faster
      throughout the entire structure of [C65S, C72S] RNase A than in wt RNase A. More
      generally, our study indicates that the C65-C72 disulfide bond of RNase A
      contributes significantly in stabilizing the structure of the hydrophobic core of
      the native protein. Formation of this disulfide bond in the final step of this
      oxidative folding pathway provides significant stabilization of the native-like
      structure that is present in the corresponding three-disulfide folding
      intermediate.

PMID- 9188688
TI  - Purification, characterization, and synthesis of an inward-rectifier K+ channel
      inhibitor from scorpion venom.
AB  - We have purified a protein inhibitor of an inward-rectifier K+ channel, ROMK1,
      from the venom of the scorpion Leiurus quinquestriatus var. hebraeus. The
      inhibitor is Lq2, a previously discovered blocker of voltage- and Ca2+-activated
      K+ channels. Mutations were made on the channel and the inhibitor, and the
      resulting effects were examined using an electrophysiological assay. The data
      show that Lq2 blocks the pore of ROMK1, and that the interaction surface on Lq2
      is the same for binding to inward-rectifier, voltage-activated, or Ca2+-activated
      K+ channels. These findings support the notion that different classes of K+
      channels have different gates but a similar K+-selective pore structure.

PMID- 9188689
TI  - Remote conformational effects of the Gly-62 --> Leu mutation of the Tn10-encoded
      metal-tetracycline/H+ antiporter of Escherichia coli and its second-site
      suppressor mutation.
AB  - Substitution of Gly-62 of the Tn10-encoded metal-tetracycline/H+ antiporter
      caused a functional defect corresponding to the volume of the substituent
      [Yamaguchi, A., Someya, Y., and Sawai, T. (1992) J. Biol. Chem. 267, 19155
      19162]. A spontaneous revertant exhibiting tetracycline resistance was isolated
      from Escherichia coli cells carrying the tetA(B) gene encoding the G62L mutation.
      The revertant showed a second-site mutation at codon 30 of TTA (Leu) to TCA
      (Ser). Site-directed mutagenesis studies revealed that the L30S mutation could
      suppress the effects of the G62A, G62C, G62N, and G62V mutations as well as the
      G62L mutation. Positions 62 and 30 are located in hydrophilic loops estimated to
      be in the cytoplasm and periplasm, respectively. Their sidedness was confirmed by
      the fact that, in intact cells, the [14C]N-ethylmaleimide (NEM) binding to the
      G62C mutant was not affected by preincubation with a membrane-impermeant
      sulfhydryl reagent, whereas the binding to the L30C mutant was blocked by the
      reagent. The reactivity of the L30C and L29C mutants with [14C]NEM was
      drastically decreased when Gly-62 was replaced by Leu, indicating that the
      residues around position 30 became embedded in the intramembrane region due to
      the remote conformational effect of the G62L mutation across the membrane.
      Moreover, the reactivity of the L29C/G62L mutant with [14C]NEM was restored with
      the L30S mutation. These results clearly indicate that the second-site
      suppression by the L30S mutation was based on the blocking of the remote
      conformational change around position 30 across the cell membrane caused by the
      G62L mutation.

PMID- 9188690
TI  - Expression, purification, and characterization of enzyme IIA(glc) of the
      phosphoenolpyruvate:sugar phosphotransferase system of Mycoplasma capricolum.
AB  - The gene encoding enzyme IIA(glc) (EIIA) of the phosphoenolpyruvate:sugar
      phosphotransferase system of Mycoplasma capricolum was cloned into a regulated
      expression vector. The purified protein product of the overexpressed gene was
      characterized as an active phosphoacceptor from HPr with a higher pI than
      previously described EIIAs. M. capricolum EIIA was unreactive with antibodies
      directed against the corresponding proteins from either Gram-positive or Gram
      negative bacteria. Enzyme IIA(glc) behaved as a homogeneous, monomeric species of
      16,700 Mr in analytical ultracentrifugation. The circular dichroism far-UV
      spectrum of EIIA reflects a low alpha-helical content and predominantly beta
      sheet structural content: temperature-induced changes in ellipticity at 205 nm
      showed that the protein undergoes reversible, two-state thermal unfolding with Tm
      = 70.0 +/- 0.3 degrees C and a van't Hoff deltaH of 90 kcal/mol. Enzyme I (64,600
      Mr) from M. capricolum exhibited a monomer-dimer-tetramer association at 4 and 20
      degrees C with dimerization constants of log K(A) = 5.6 and 5.1 [M(-1)],
      respectively, in sedimentation equilibrium experiments. A new vector, capable of
      introducing an N-terminal His tag on a protein, was developed in order to
      generate highly purified heat-stable protein (HPr). No significant interaction of
      EIIA with HPr was detected by gel-filtration chromatography, intrinsic
      tryptophanyl residue fluorescence changes, titration calorimetry, biomolecular
      interaction, or sedimentation equilibrium studies. While Escherichia coli EIIA
      inhibits Gram-negative glycerol kinase activity, the M. capricolum EIIA has no
      effect on the homologous glycerol kinase. The probable regulator of sugar
      transport systems, HPr(Ser) kinase, was demonstrated in extracts of M. capricolum
      and Mycoplasma genitalium. Gene mapping studies demonstrated that, in contrast to
      the clustered arrangement of genes encoding HPr and enzyme I in E. coli, these
      genes are located diametrically opposite in the M. capricolum chromosome.

PMID- 9188691
TI  - Regulation of glycogen utilization, but not glucose utilization, by
      precontraction glycogen levels in vascular smooth muscle.
AB  - These experiments were designed to determine whether glycogenolysis was
      influenced by the glycogen concentration of vascular smooth muscle. Segments of
      hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1
      [13C]glucosyl units of glycogen. Artery segments were then isometrically
      contracted in the presence of 2-[13C]glucose. Prior to and after isometric
      contraction, measurements were made of tissue glycogen content and superfusate
      glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak
      intensities in the superfusate were measured using 13C-NMR spectroscopy. The
      tissue glycogen content decreased exponentially during the 4.5 h of isometric
      contraction (R2 = 0.990), despite more than a 3-fold range of glycogen
      concentration prior to contraction. The extent of glycogen utilization during a 3
      h isometric contraction varied linearly with the precontraction glycogen
      concentration (R2 = 0.727). Lactate production specifically from glycogen
      breakdown increased with an increase in precontraction glycogen concentration (R2
      = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2
      = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002)
      varied with the precontraction glycogen concentration. It is concluded that the
      rate of glycogenolysis is determined by the content of glycogen during prolonged
      contractions. In addition, precontraction glycogen levels influence the pathway
      for glycogen utilization but not the pathway for glucose utilization. Therefore,
      glycolysis and glycogenolysis behave independently in vascular smooth muscle.

PMID- 9188692
TI  - The product of the MLD gene is a member of the membrane fatty acid desaturase
      family: overexpression of MLD inhibits EGF receptor biosynthesis.
AB  - Membrane fatty acid desaturases are responsible for inserting double bonds into
      specific positions in fatty acids. We have cloned a new member of the human
      membrane fatty acid (lipid) desaturase gene family, MLD. The derived amino acid
      sequence of MLD contains three consensus motifs, HX3H, HX2HH, and HX2HHXFP, that
      are characteristic of a group of membrane fatty acid desaturases. MLD is
      predicted to be a multiple membrane-spanning protein and is found to be
      extractable from particulate fractions with detergent but not salt or urea. MLD
      is widely expressed in human tissues and is localized to the endoplasmic
      reticulum. Cotransfection of MLD with the epidermal growth factor (EGF) receptor
      resulted in decreased expression of the receptor but did not affect platelet
      derived growth factor receptor expression. MLD overexpression inhibited
      biosynthesis of the EGF receptor, suggesting a possible role of a fatty acid
      desaturase in regulating biosynthetic processing of the EGF receptor.

PMID- 9188693
TI  - The C-terminal region of nisin is responsible for the initial interaction of
      nisin with the target membrane.
AB  - The interaction of nisin Z and a nisin Z mutant carrying a negative charge in the
      C-terminus ([Glu-32]-nisin Z) with anionic lipids was characterized in model
      membrane systems, and bacterial membrane systems. We focused on three possible
      steps in the mode of action of nisin, i.e., binding, insertion, and pore
      formation of nisin Z. Increasing amounts of anionic lipids in both model and
      natural membranes were found to strongly enhance the interaction of nisin Z with
      the membranes at all stages. The results reveal a good correlation between the
      anionic lipid dependency of the three stages of interaction, of which the
      increased binding is probably the major determinant for antimicrobial activity.
      Maximal nisin Z activity could be observed for negatively charged lipid
      concentrations exceeding 50-60%, both in model membrane systems as well as in
      bacterial membrane systems. We propose that the amount of negatively charged
      lipids of the bacterial target membrane is a major determinant for the
      sensitivity of the organism for nisin. Nisin Z induced leakage of the anionic
      carboxyfluorescein was more efficient as compared to the leakage of the potassium
      cation. This lead to the conclusion that an anion-selective pore is formed. In
      contrast to the results obtained for nisin Z, the binding of [Glu-32]-nisin Z to
      vesicles remained low even in the presence of high amounts of negatively charged
      lipids. The insertion and pore-forming ability of [Glu-32]-nisin Z were also
      decreased. These results demonstrate that the C-terminus of nisin is responsible
      for the initial interaction of nisin, i.e., binding to the target membrane.

PMID- 9188694
TI  - Comparison of the salt-dependent self-association of brain and erythroid
      spectrin.
AB  - The self-association of ovine brain spectrin in 0.1-1.5 M NaCl (pH 7.5) was
      studied using sedimentation velocity and sedimentation equilibrium techniques.
      Brain spectrin is tetrameric at sedimentation equilibrium at a 0.13 M ionic
      strength at 18-37 degrees C and at ionic strengths of up to 0.33 M at 20 degrees
      C. At ionic strengths greater than 0.33 M at 20 degrees C, the brain spectrin
      tetramer is destabilized, resulting in both dissociation to dimers and indefinite
      association to higher oligomers, in a manner similar to that seen with erythroid
      spectrin. The equilibrium constants describing all steps in the association
      involving the addition of dimers are around 15-fold higher for brain spectrin
      than for erythroid spectrin, at ionic strengths of > or = 0.43 M. We propose that
      the stronger association of brain spectrin compared to that of erythroid spectrin
      is due to a relative inability of brain spectrin to form closed dimers.
      Sedimentation velocity analysis confirms that brain spectrin readily forms open
      dimers and that the association of open dimers is not kinetically trapped even at
      2 degrees C. Our results suggest that the destabilization of spectrin tetramers
      in high-ionic strength conditions is due to increased independent movement of the
      alpha and beta subunits resulting from disruption of electrostatic interactions.
      The greater stability of brain spectrin oligomers relative to those of erythroid
      spectrin is due to stronger nonelectrostatic interactions which stabilize the
      rigidity of the individual subunits and thereby increase the conformational
      strain associated with dimer closure.

PMID- 9188695
TI  - Conversion of protein phosphatase 1 catalytic subunit to a Mn(2+)-dependent
      enzyme impairs its regulation by inhibitor 1.
AB  - The phosphorylase phosphatase activity of protein phosphatase 1 (PP1) catalytic
      subunit from freshly purified rabbit skeletal muscle was inhibited by MnCl2.
      Prolonged storage or inhibition by nonspecific phosphatase inhibitors ATP, sodium
      pyrophosphate, and NaF converted the muscle PP1 to a form that required Mn2+ for
      enzyme activity. Recombinant PP1 catalytic subunit expressed in Escherichia coli
      was also a Mn2+-dependent enzyme. While native PP1 was inhibited by the
      phosphoprotein inhibitor I (I-1), with an IC50 of 1 nM, 40-50-fold higher
      concentrations of I-1 were required to inhibit the Mn2+-dependent PP1 enzymes.
      Conversion to the Mn2+-dependent state was accompanied by a 20-fold increase in
      PP1's ability to dephosphorylate and inactivate I-1. Inhibition by
      thiophosphorylated I-1 established that dephosphorylation does not play a
      significant role in I-1's reduced potency as an inhibitor of Mn2+-dependent PP1.
      The Mn2+-dependent PP1 enzymes were poorly inhibited by N-terminal
      phosphopeptides of I-1, indicating their impaired interaction with the I-1
      functional domain. Mutation of a residue conserved in I-1 and DARPP-32, a
      structurally related PP1 inhibitor, preferentially attenuated I-1's activity as
      an inhibitor of Mn2+-dependent PP1. These data showed that, in addition to
      changes in its catalytic properties, Mn2+-dependent PP1 was modified in its
      interaction with I-1 at a site that was distinct from its catalytic domain. Our
      studies suggest that conversion to a Mn2+-dependent state alters multiple
      structural elements in PP1 catalytic subunit that together define its regulation
      by I-1.

PMID- 9188696
TI  - Myristoylated and nonmyristoylated pools of sea urchin sperm flagellar creatine
      kinase exist side-by-side: myristoylation is necessary for efficient lipid
      association.
AB  - In sperm of the sea urchin Strongylocentrotus purpuratus, a functional
      phosphocreatine shuttle, that requires the existence of mitochondrial and
      cytosolic creatine kinase (CK) isoforms in distinct locations, is essential for
      sperm motility. S. purpuratus sperm have an unusually large, 145 kDa CK isoform,
      present exclusively in the sperm tail (TCK), that is enriched in flagellum
      membrane preparations. Purified TCK contains two very similar proteins,
      designated TCKI and TCKII, of which only TCKII associates readily with liposomes
      and detergent micelles in vitro. Here we demonstrate by gas chromatography/mass
      spectrometry combined with selective ion monitoring that ions diagnostic for the
      presence of myristoylglycine in proteins are found in TCKII, but not TCKI. By
      contrast, TCKI, but not TCKII, served in vitro as a substrate for recombinant,
      polyhistidine-tagged N-myristoyltransferase and was myristoylated to high
      stoichiometries (0.58 +/- 0.14 pmol of myristate/pmol of TCK), in the presence of
      myristoyl-CoA, on glycine in amide linkage. In vitro myristoylated TCKI
      associated with phosphatidylcholine (PC)/phosphatidylserine (PS) (75:25)
      liposomes and Triton X-100 detergent micelles in gel filtration assays and with
      PC/PS liposomes in a centrifugation assay in the same manner as did TCKII. In gel
      filtration experiments, TCKI required at least 25-fold higher PC/PS liposome
      concentrations than TCKII to obtain 50% association. A partition coefficient of
      0.8 x 10(5) M(-1) was determined for TCKII with PC/PS (75:25) liposomes in the
      centrifugation assay. Thus, myristoylated and nonmyristoylated forms of TCK exist
      side-by-side in the sea urchin flagellum, and myristoylation is essential for
      efficient liposome association of TCK.

PMID- 9188698
TI  - Mutagenesis studies of thyroxine binding to human serum albumin define an
      important structural characteristic of subdomain 2A.
AB  - The familial dysalbuminemic hyperthyroxinemia (FDH) phenotype results from a
      natural human serum albumin (HSA) mutant, with histidine instead of arginine at
      amino acid position 218. This mutation results in an enhanced affinity for
      thyroxine. In our earlier study, site-directed mutagenesis and a yeast protein
      expression system were used to synthesize FDH HSA and several other HSA mutants.
      Measurement of the binding of these HSA mutants to thyroxine and several
      thyroxine analogs using equilibrium dialysis and quenching of tryptophan 214
      fluorescence allowed us to propose a preliminary model of thyroxine binding to
      the 2A subdomain of wild type and FDH HSA. In this study, we have produced
      several other HSA mutants. By comparing the binding affinity of these mutants for
      thyroxine and tetraiodothyroacetic acid to the binding affinity of other mutants,
      we were able to suggest a new model for thyroxine binding to the 2A subdomain of
      HSA. We found that the substitution of arginine at position 218 with alanine
      increased the binding affinity for thyroxine by 2 orders of magnitude relative to
      the binding affinity of wild type HSA for thyroxine. A more accurate
      understanding of the mechanism of thyroxine binding to HSA has allowed us to
      define an important structural characteristic of subdomain 2A, one of the two
      principal binding sites on HSA for small hydrophobic ligands.

PMID- 9188697
TI  - Differences in water release with DNA binding by ultrabithorax and deformed
      homeodomains.
AB  - The amino acid sequences of the homeodomains (HD) within the Ultrabithorax (Ubx)
      and Deformed (Dfd) proteins from Drosophila melanogaster are highly conserved
      despite distinct genetic regulatory functions for these proteins in embryonic
      development. We reported recently that Ubx-HD binding to a single target site
      displayed significantly increased affinity and greater salt concentration
      dependence at lower pH; in contrast, Dfd-HD did not show pH dependence in its DNA
      binding properties [Li, L., et al. (1996) Biochemistry 35, 9832-9839]. We
      demonstrate in this study that water activity differentially affects Ubx-HD and
      Dfd-HD DNA binding affinity. The sensitivity of the protein-DNA binding constant
      to osmotic pressures generated by neutral solutes was measured, and the formation
      of the Ubx-HD-DNA complex is associated with significantly greater water release
      than that of the Dfd-HD-DNA complex. No influence of pH on water release was
      detected for either HD. Experiments with chimeric Ubx-Dfd homeodomains
      demonstrated that the C-terminal region of the Ubx-HD is the primary determinant
      for the greater water release associated with DNA binding for this protein. DNA
      sequences do not exert a significant effect on the magnitude of water release
      associated with protein-DNA binding for Ubx-HD and the chimeric HD, UDU.

PMID- 9188699
TI  - Alternate amino terminal processing of surfactant protein A results in cysteinyl
      isoforms required for multimer formation.
AB  - The biological functions of rat surfactant protein A (SP-A), an oligomer composed
      of 18 polypeptide subunits derived from a single gene, are dependent on intact
      disulfide bonds. Reducible and collagenase-reversible covalent linkages of as
      many as six or more subunits in the molecule indicate the presence of at least
      two NH2-terminal interchain disulfide bonds. However, the reported primary
      structure of rat SP-A predicts that only Cys6 in this region is available for
      interchain disulfide formation. Direct evidence for a second disulfide bridge was
      obtained by analyses of a set of three mutant SP-As with telescoping deletions
      from the reported NH2-terminus. Two of the truncated recombinant proteins formed
      reducible dimers despite deletion of the domain containing Cys6. Edman
      degradation revealed that each mutant protein was a mixture of two isoforms with
      and without an isoleucine-lysine-cysteine (IKC) extension at the NH2-terminus,
      which was derived from the COOH-terminal end of the reported signal peptide.
      Large variations in the abundance of the IKC isoforms between truncated SP-As
      suggested that the amino acid sequences located downstream from the signal
      peptide modulated alternate-site cleavage by signal peptidase. Elution of the
      newly identified cysteine in the position of DiPTH-Cys indicated participation in
      disulfide linkage, which was interchain based on the direct correlation between
      prevalence of the IKC variant and the extent of dimerization for each truncated
      protein. Sequencing of both native rat SP-A and human SP-A also revealed isoforms
      with disulfide-forming NH2-terminal extensions. The extended rat SP-A isoforms
      were enriched in the more fully glycosylated and multimeric SP-A species
      separated on SDS-PAGE gels. Thus, a novel post translational modification results
      in naturally occurring cysteinyl isoforms of rat SP-A, which are essential for
      multimer formation.

PMID- 9188700
TI  - In vitro biosynthesis of a decasaccharide prototype of multiply branched
      polylactosaminoglycan backbones.
AB  - Multiply branched polylactosaminoglycans are expressed in glycoproteins and
      glycolipids of many cells. Interest in their biology stems from their abundant
      expression in early embryonal cells and from their ability to carry multiple
      lectin-binding determinants, which makes them prominent ligands and antagonists
      of cell adhesion proteins. A prototype of their backbones is represented by the
      decasaccharide LacNAc beta1-3'(LacNAc beta1-6')LacNAc beta1-3'(LacNAc beta1
      6')LacNAc (5), where LacNAc is the disaccharide Gal beta1-4GlcNAc. Here, we
      describe in vitro biosynthesis of glycan 5. Incubation of the linear
      hexasaccharide LacNAc beta1-3'LacNAc beta1-3'LacNAc (1) with UDP-GlcNAc and alpha
      midchain beta1,6-GlcNAc transferase activity (GlcNAc to Gal), present in rat
      serum [Gu, J., Nishikawa, A., Fujii, S., Gasa, S., & Taniguchi, N. (1992) J.
      Biol. Chem. 267, 2994-2999], gave the doubly branched octasaccharide LacNAc beta1
      3'(GlcNAc beta1-6')LacNAc beta1-3'(GlcNAc beta1-6')LacNAc (4). The latter was
      converted to 5 by enzymatic beta1,4-galactosylation. In the initial branching
      reaction of 1, two isomeric heptasaccharide intermediates, LacNAc beta1-3'LacNAc
      beta1-3'(GlcNAc beta1-6')LacNAc (2) and LacNAc beta1-3'(GlcNAc beta1-6')LacNAc
      beta1-3'LacNAc (3), were formed first at comparable rates. Later, both
      intermediates were converted to 4, revealing two distinct pathways of the
      reaction: 1 --> 2 --> 4 and 1 --> 3 --> 4. These data suggest that, regardless of
      their chain length, linear polylactosamines similar to 1 contain potential
      branching sites at each of the internal galactoses. The enzyme-binding epitope of
      1 is probably LacNAc beta1-3'LacNAc, because the trisaccharides GlcNAc beta1
      3'LacNAc and LacNAc beta1-3Gal as well as the tetrasaccharide GlcNAc beta1
      3'LacNAc beta1-3Gal were poor acceptors, while LacNAc beta1-3'LacNAc was a good
      one. Midchain beta1,6-GlcNAc transferase activities present in serum of several
      mammalian species, including man, resembled closely the rat serum activity in
      their mode of action and in their acceptor specificity. We suggest that analogous
      membrane-bound Golgi enzymes are involved in the biosynthesis of multiply
      branched polylactosamines in vivo.

PMID- 9188701
TI  - Functional role of leucine-103 in myohemerythrin.
AB  - Hemerythrins (Hrs) and myohemerythrins (Mhrs) are nonheme iron proteins that
      function as O2 carriers in four marine invertebrate phyla. Available amino acid
      sequences and X-ray structures indicate that a conserved leucine, residue 103 in
      the Themiste zostericola Mhr sequence, occupies a site distal to the Fe-O-Fe
      center. The side-chain methyl groups of the analogous leucine in Themiste
      dyscrita oxyHr are in van der Waals contact with bound O2 in the X-ray crystal
      structure, and this residue may therefore play a role in stabilizing bound
      dioxygen with respect to autoxidation. In order to test this hypothesis, the gene
      for T. zostericola Mhr was synthesized and expressed in Escherichia coli. Two
      mutant Mhrs, L103V and L103N, were also prepared. Optical spectra and kinetics
      data for these three proteins are presented. Importantly, neither mutant forms a
      stable oxy adduct; instead, rapid autoxidation results in formation of the
      corresponding met forms. In addition, the L103N Mhr displays unusually rapid
      reduction kinetics, suggesting that the amide functionality of Asn-103
      destabilizes most bound ligands and additionally promotes rapid semi-metR <==>
      semi-metO isomerization.

PMID- 9188702
TI  - Structures of wild-type chloromet and L103N hydroxomet Themiste zostericola
      myohemerythrins at 1.8 A resolution.
AB  - Myohemerythrin (Mhr) is a nonheme iron oxygen carrier found in the retractor
      muscles of marine "peanut" worms. The X-ray crystal structures of two recombinant
      Themiste zostericola Mhrs are reported to a resolution of 1.8 A. Surprisingly,
      the met wild-type structure (R = 17.8%) was found to contain chloride bound to
      Fe2, while coordinated hydroxide was found in the met L103N structure (R =
      18.3%). An internal water molecule was also found distal to the Fe-O-Fe center of
      the mutant protein, forming hydrogen bonds with the coordinated hydroxide and the
      OD1 atom of Asn-103. This finding is consistent with the kinetic and
      spectroscopic results reported for the L103N mutant Mhr [Raner, G. M., Martins,
      L. J., & Ellis, W. R., Jr. (1997) Biochemistry 36, 7037-7043]. Possible roles for
      the side chain of residue 103 (Leu in wild-type Mhr) in gating ligand binding are
      also discussed.

PMID- 9188703
TI  - Purification and characterization of an extracellular heme-binding protein, HasA,
      involved in heme iron acquisition.
AB  - Many bacterial hemoproteins involved in heme acquisition have been isolated
      recently, comprising outer membrane receptors and extracellular heme-binding
      protein. The mechanisms by which these proteins extract heme have not been
      described up to now. One such protein, HasA, which can bind free heme as well as
      capture it from hemoglobin, is secreted by the Gram-negative bacteria Serratia
      marcescens under iron deficiency conditions. The fact that HasA does not present
      sequence similarities with other known hemoproteins suggests that it possesses a
      new type of heme binding site. This work describes the main physicochemical
      properties of HasA, essential for understanding its function. HasA is a monomer
      of 19 kDa that binds one b heme per molecule with high affinity. The electron
      paramagnetic resonance spectra indicate that the heme iron is in a low-spin
      ferric state and that the two iron axial ligands are His and His-. The low
      oxidation-reduction potential value (-550 mV vs standard hydrogen electrode) of
      the heme bound to HasA suggests that heme could be exposed to the solvent.
      According to circular dichroism data, the binding of heme does not seem to modify
      the conformation of HasA.

PMID- 9188704
TI  - Arrestin with a single amino acid substitution quenches light-activated rhodopsin
      in a phosphorylation-independent fashion.
AB  - Arrestins are members of a superfamily of regulatory proteins that participate in
      the termination of G protein-mediated signal transduction. In the
      phototransduction cascade of vertebrate rods, which serves as a prototypical G
      protein-mediated signaling pathway, the binding of visual arrestin is stimulated
      by phosphorylation of the C-terminus of photoactivated rhodopsin (Rh*). Arrestin
      is very selective toward light-activated phosphorhodopsin (P-Rh*). Previously we
      reported that a single amino acid substitution in arrestin, Arg175Gln, results in
      a dramatic increase in arrestin binding to Rh* [Gurevich, V. V., & Benovic, J. L.
      (1995) J. Biol. Chem. 270, 6010-6016]. Here we demonstrate that a similar mutant,
      arrestin(R175E), binds to light-activated rhodopsin independent of
      phosphorylation. Arrestin(R175E) binds with high affinity not only to P-Rh* and
      Rh* but also to light-activated truncated rhodopsin in which the C-terminus
      phosphorylation sites have been proteolytically removed. In an in vitro assay
      that monitored rhodopsin-dependent activation of cGMP phosphodiesterase (PDE),
      wild type arrestin quenched PDE response only when ATP was present to support
      rhodopsin phosphorylation. In contrast, as little as 30 nM arrestin(R175E)
      effectively quenched PDE activation in the absence of ATP. Arrestin(R175E) had no
      effect when the lifetime of Rh* no longer contributed to the time course of PDE
      activity, suggesting that it disrupts signal transduction at the level of
      rhodopsin-transducin interaction.

PMID- 9188705
TI  - In vitro assay for trans-phosphorylation of rhodopsin by rhodopsin kinase.
AB  - Trans-phosphorylation of rhodopsin refers to a reaction in which a rhodopsin
      kinase molecule that has been activated by a light-activated rhodopsin molecule
      collides with and phosphorylates a second molecule of rhodopsin that has not been
      activated by light. It has been invoked as a mechanism for high-gain
      phosphorylation, a phenomenon that is observed at low bleaching levels where up
      to several hundred moles of phosphate are added to the rhodopsin pool per mole of
      photolyzed rhodopsin. Trans-phosphorylation is an appealing mechanism to propose
      for high-gain phosphorylation, but it has not been tested directly because of the
      difficulty inherent in unambiguous identification of light-activated and dark
      forms of rhodopsin present in the same reaction mixture. We report here a direct
      assay for trans-phosphorylation of rhodopsin. The assay is based on the use of a
      split receptor mutant of rhodopsin, SR(1-4/5-7), in which the fully functional
      protein is assembled from two separately expressed fragments. Because of
      different electrophoretic mobilities, SR(1-4/5-7) and wild-type rhodopsin can be
      monitored independently for phosphorylation while in the same reaction mixture.
      Thus, if wild-type rhodopsin is exposed to light and then incubated in the dark
      with SR(1-4/5-7), ATP, and rhodopsin kinase, phosphorylation of SR(1-4/5-7) would
      be a clear demonstration that trans-phosphorylation has occurred. Despite
      numerous attempts using several different experimental configurations, we have
      been unable to detect trans-phosphorylation of dark rhodopsin with this system.

PMID- 9188706
TI  - Regulation of the mitochondrial Ca2+ uniporter by external adenine nucleotides:
      the uniporter behaves like a gated channel which is regulated by nucleotides and
      divalent cations.
AB  - We have previously used measurements of uncoupler-enforced reverse activity to
      demonstrate that the mitochondrial Ca2+ uniporter is strongly inhibited by
      external EGTA plus free Mg2+, following a brief period of rapid activity. Using
      the same approach, we now show that in addition to divalent cations, the
      uniporter is regulated by external adenine nucleotides and by other components of
      the cytosol. Inhibition produced by EGTA plus free Mg2+ is reversed by spermine
      (EC0.5 approximately 40 microM) and reduced when mitochondria are purified by an
      isoosmotic density-gradient method. Under either condition, inhibition is
      restored by external adenine nucleotides in a concentration-dependent manner. The
      order of effectiveness is ATP > ADP > AMP, with the nucleoside adenosine being
      ineffective. Among nucleotide triphosphates, the order is ATP > CTP approximately
      UTP > GTP. The effectiveness of ATP (EC50 approximately 0.6 mM) is the same in
      mitochondria and mitoplasts, the same as that of AMPPNP, and is not altered by
      the presence of oligomycin, carboxyatractyloside, or AP5A, used alone or in
      combinations. These findings indicate that ATP acts at a site located on the
      outer surface of the inner membrane through a mechanism which does not require
      its hydrolysis. Phosphate also inhibits reverse uniport under some conditions
      (EC50 approximately 20 microM). The sites at which free ATP and free Mg2+ inhibit
      the uniporter can be distinguished by chymotrypsin treatment of mitoplasts, which
      eliminates the action of Mg2+ but does not affect the action of ATP. Data are
      interpreted within the context of a model in which the uniporter is considered to
      be a gated channel that is controlled, in part, by specific external effector
      sites that accept divalent cations or nucleotides. The possible consequences of
      the model for cell Ca2+ regulation by mitochondria and regulation of TCA cycle
      activity by the matrix free Ca2+ concentration are considered.

PMID- 9188707
TI  - Factors controlling the substrate specificity of peroxidases: kinetics and
      thermodynamics of the reaction of horseradish peroxidase compound I with phenols
      and indole-3-acetic acids.
AB  - The rates of oxidation of reducing substrates by heme peroxidases have previously
      been thought to be controlled only by their ease of oxidation. In the present
      study, we have compared the kinetics and thermodynamics of the oxidation of
      indole-3-acetic acid and derivatives and of phenols by horseradish peroxidase.
      Different dependencies of the reaction rates on the thermodynamic driving force
      reveal substrate specificity controlled by the enzyme-substrate complexes
      dissociation constants (Michaelis-Menten constants) and by the reorganization
      energies of electron-transfer within those complexes.

PMID- 9188708
TI  - EPR investigation of water oxidizing photosystem II: detection of new EPR signals
      at cryogenic temperatures.
AB  - Experiments are described which allow the detection and characterization of new
      EPR signals in photosystem II (PSII). PSII has been extensively studied with the
      water oxidising complex (WOC) poised in the S1 and S2 states. Other stages in the
      cycle of water oxidation lack characteristic EPR signals for use as probes. In
      this study, experiments use multiple turnovers of PSII from an initial S1 state
      to allow new states of PSII to be studied. The first EPR signal detected,
      centered at g = 4.85 and termed the g = 5 signal, is suggested to be a new form
      of S2 probably formed by decay of S3 at cryogenic temperatures, but a novel form
      of oxidized non-heme iron cannot be fully excluded at present. The second signal
      is split around g = 2 and shows characteristics of signals formed by spin-spin
      interaction between two paramagnetic species. The split g = 2 signal is
      reversibly formed by illumination at <30 K of a sample containing the g = 5
      signal. The g = 2 signal may be a form of the "S3" EPR signal previously only
      found in a variety of PSII preparations where oxygen evolution has been
      inhibited. Those "S3" signals are thought to arise from the interaction of an
      oxidized amino acid radical and the S2 state, i.e., S2X+. Illumination at higher
      temperatures or illumination at <30 K, followed by dark-adaptation at 77 K,
      removes the g = 5 signal and prevents subsequent detection of the g = 2 signal on
      illumination at <30 K. The most likely explanation of our data is that
      illumination at <30 K of centers containing the g = 5 species allows accumulation
      of an oxidized intermediate and that at higher temperatures electron transfer
      proceeds to re-form an EPR-silent S state equivalent to that initially trapped
      during sample preparation. Study of these signals should provide an important new
      insight into the WOC and PSII.

PMID- 9188709
TI  - Trehalose prevents myoglobin collapse and preserves its internal mobility.
AB  - A quantitative model, which involves diffusion on a temperature-dependent
      potential, is utilized to analyze the time-dependence of geminate CO
      recombination to sperm whale myoglobin in a trehalose glass and the accompanying
      spectral shifts. Most of the recombination is inhomogeneous. This is due to
      higher geminate reactivity rather than slower protein relaxation. A fraction of
      the hemes undergoes relaxation with a concomitant increase in the barrier height
      for recombination. The activation energy for conformational diffusion
      (relaxation) is considerably lower than in glycerol/water. "Protein collapse",
      manifested in glycerol/water by a decrease in the equilibrium conformational
      separation between the bound and deoxy states, is completely prevented in
      trehalose. We postulate that the high internal viscosity in glycerol/water is due
      to dehydration of the heme pocket. Trehalose prevents the escape of the few vital
      internal water molecules and thus preserves the internal lability of the protein.
      This might be important in understanding the ability of trehalose to protect
      against the adverse effects of dehydration.

PMID- 9188710
TI  - Spectroscopic characterization of recombinant Cu,Zn superoxide dismutase from
      Photobacterium leiognathi expressed in Escherichia coli: evidence for a novel
      catalytic copper binding site.
AB  - Cu,Zn superoxide dismutase from Photobacterium leiognathi has been cloned and
      expressed in Escherichia coli. The circular dichroism spectrum in the UV region
      of the recombinant protein indicates an higher content of random coil structure
      with respect to the eukaryotic enzymes. Investigation of the active site by
      optical, CD, and EPR spectroscopy indicates a different coordination geometry
      around the catalytic copper site with respect to the eukaryotic enzymes. In
      particular a different orientation of the metal bridging histidine is suggested.
      The pH dependence of the copper EPR spectrum shows the presence of a single
      equilibrium which is at least one unit lower than the pK value observed for the
      bovine enzyme. Despite such structural differences the catalytic rate of this
      enzyme is identical to that observed for the eukaryotic Cu,Zn superoxide
      dismutase, suggesting that the overall electric field distribution is similar to
      that observed in the eukaryotic enzymes.

PMID- 9188711
TI  - Resonance Raman spectral properties and stability of manganese protoporphyrin IX
      cytochrome b5.
AB  - The structure and stability of cytochrome b5 reconstituted with manganese
      protoporphyrin IX instead of iron protoporphyrin IX has been investigated by
      resonance Raman spectroscopy and stopped-flow visible spectroscopy. The resonance
      Raman spectrum of MnIII cytochrome b5 was consistent with a high-spin
      hexacoordinate MnIII protoporphyrin IX structure that converted to a high-spin
      pentacoordinate structure at higher laser power. The resonance Raman spectrum of
      MnII cytochrome b5 indicated a high-spin pentacoordinate structure which was
      independent of laser power. Studies of the binding of MnIII protoporphyrin IX to
      apocytochrome b5 indicated that the MnIII-containing porphyrin bound much less
      tightly to the protein than did heme. Although the second-order rate constant at
      20 degrees C for the association of heme with apocytochrome b5 (4.5 x 10(7) M(-1)
      s(-1)) was estimated to be only 1 order of magnitude higher than that with Mn
      protoporphyrin IX (3.3 x 10(6) M(-1) s(-1)), the dissociation of manganese
      substituted cytochrome b5 into the apoprotein and free Mn protoporphyrin IX
      occurs with a first-order rate constant of 1.2 x 10(-2) s(-1) at 20 degrees C
      while the dissociation of heme from cytochrome b5 at room temperature occurs 3
      orders of magnitude more slowly with a first-order rate constant of 1.67 x 10(-5)
      s(-1) [Vergeres, G., Chen, D. Y., Wu, F.F., & Waskell, L. (1993) Arch. Biochem.
      Biophys. 305, 231-241]. The equilibrium dissociation constant for manganese
      substituted cytochrome b5 increased with temperature from 4 nM at 20 degrees C to
      14 nM at 37 degrees C. These results suggest that, in the reconstituted
      cytochrome P450 metabolizing system, especially in studies done with low protein
      concentrations (0.1 microM), and at elevated temperatures (37 degrees C), as much
      as 30% of the manganese-substituted cytochrome b5 may dissociate to free Mn
      protoporphyrin IX and apocytochrome b5.

PMID- 9188712
TI  - Molecular interpretation of inhibition by excess substrate in flavocytochrome b2:
      a study with wild-type and Y143F mutant enzymes.
AB  - The crystal structure of flavocytochrome b2 (L-lactate dehydrogenase) from
      Saccharomyces cerevisiae suggests that Tyr143 plays a dual role at the active
      site: it contributes to substrate binding and, most importantly, makes a hydrogen
      bond to a heme propionate, which could facilitate communication between the
      domains. Previous work on the Y143F mutant enzyme provided support for these
      hypotheses [Miles, C. S., Rouviere-Fourmy, N., Lederer, F., Mathews, F. S., Reid,
      G. A., Black, M. T., & Chapman, S. K. (1992) Biochem. J. 285, 187-192; Rouviere
      Fourmy, N., Capeillere-Blandin, C., & Lederer, F. (1994) Biochemistry 33, 798
      806]. In the course of kinetic comparisons between the wild-type (WT) enzyme and
      the Y143F mutant protein, we observed for the latter signs of inhibition by
      excess substrate at much lower concentrations than observed for the former. A
      detailed investigation of the phenomenon has shown that, for the wild-type and
      Y143F forms, lactate at high concentrations inhibits both cytochrome c and
      ferricyanide reduction. In these cases, inhibition appears to be a specific
      effect, since acetate at identical concentrations exerts an inhibitory effect
      that is markedly weaker than that of lactate. In the pre-steady-state, in the
      absence of acceptor, flavin and heme reduction are unaffected by high substrate
      concentrations in the WT enzyme case. For the Y143F mutant, flavin reduction is
      similarly unaffected, but heme reduction is inhibited to nearly the same extent
      by high lactate and acetate concentrations. In this case, inhibition can probably
      be ascribed to ionic strength effects. The combination of stopped-flow and steady
      state results suggests that lactate binds with weak affinity at the active site
      when the flavin is in the semiquinone state, preventing electron transfer to heme
      b2 and hence to acceptors. This phenomenon is analogous to the inhibition exerted
      by pyruvate when bound to the enzyme at the semiquinone stage [Tegoni, M., Janot,
      J. M., & Labeyrie, F. (1990) Eur. J. Biochem. 190, 329-342]. We suggest that the
      substrate carboxylate and the heme propionate of the mobile heme-binding domain
      compete for the Tyr143 hydroxyl group, hence for approach to the flavin. In the
      Y143F mutant enzyme, in which the interdomain interaction is impaired,
      competition would play in favor of the substrate, resulting in the inhibition at
      lower lactate concentrations than observed for the wild-type enzyme.

PMID- 9188713
TI  - Intramolecular isotope effects for benzylic hydroxylation of isomeric xylenes and
      4,4'-dimethylbiphenyl by cytochrome P450: relationship between distance of methyl
      groups and masking of the intrinsic isotope effect.
AB  - Intramolecular isotope effects associated with the benzylic hydroxylation of a
      series of selectively deuterated isomeric xylenes and 4,4'-dimethylbiphenyl as
      catalyzed by various rat liver microsomal preparations and CYP2B1 were
      determined. Substrate analogs in which each methyl group contained either one (d2
      substrates) or two (d4 substrates) deuterium atoms were used to determine the
      intrinsic isotope effect for the reaction. Specific values of the individual
      primary (P) and secondary isotope effects (S) were determined. P ranged from a
      low of 5.32 +/- 0.48 to a high of 7.57 +/- 0.42 depending upon the specific
      cytochrome P450 preparation used for catalysis. S had an average value of 1.03.
      The d3 substrates allowed exploration of the effect of distance on the magnitude
      of the observed isotope effect. The results indicate that the distance of 6.62 A
      that separates the carbon atoms of the para methyl groups of p-xylene is
      insufficient to suppress (mask) the intrinsic isotope effect for benzylic
      hydroxylation by all of the enzyme preparations examined. Conversely, a distance
      of 11.05 A, the minimal separation between the carbon atoms of the para methyl
      groups of p,p'-dimethylbiphenyl, is large enough to almost completely mask the
      intrinsic isotope effect for benzylic hydroxylation by the same set of enzymes.

PMID- 9188714
TI  - Chiral multisubstrate inhibitors of dopamine beta-monooxygenase: evidence for
      dual modes of interaction.
AB  - The electronic and steric constraints of the dopamine beta-monooxygenase (DbetaM;
      E.C. 1.14.17.1) active site were studied using a series of chiral bisubstrate
      inhibitors. The (R) and (S) enantiomers of 5-phenyl-2-thiooxazolidone were
      apparent bisubstrate inhibitors for DbetaM with respect to tyramine and dioxygen,
      but with small enantiomeric selectivity. In contrast to the substrate specificity
      of the enzyme, N-methylation of both inhibitors increased the potency without
      altering the enantiomeric selectivity. The (S) C-4-methyl substitution was more
      detrimental toward the inhibition potency compared to (R) C-4-methyl substitution
      for both the (R) and (S) series, which was also opposite of the substrate
      specificity of the enzyme. The high inhibition potency and apparent bisubstrate
      behavior of 3-phenyl-1,5-bisthioglutarimide (XVI), a probe designed to mimic two
      distinct binding modes for the (R) and (S) inhibitors, suggested that they may
      interact with the enzyme by two different modes involving both coppers in the
      active site. Direct support for the interaction of the thione group(s) of XVI
      with the reduced DbetaM copper(s) is provided by the UV-vis spectroscopic
      studies. The complete disappearance of the characteristic UV absorption of XVI at
      336 nm in the presence of stoichiometric amounts of reduced DbetaM demonstrate
      that it could be an active site titrant for reduced DbetaM. The ability of the
      enzyme to interact with these inhibitors by more than one mode suggests that the
      DbetaM active site possesses high steric and electronic tolerance.

PMID- 9188715
TI  - Protein-protein interactions between UDP-glucuronosyltransferase isozymes in rat
      hepatic microsomes.
AB  - The interactions between UDP-glucuronosyltransferase (UGT) isozymes, UGT1s and
      UGT2B1, in rat hepatic microsomes were investigated using an immunopurification
      technique with anti-peptide antibodies and a chemical cross-linking strategy. A
      50 kDa protein coimmunopurified with UGT1s was identified as UGT2B1 by amino
      terminal sequencing and immunodetection with anti-peptide antibody against
      UGT2B1. Evidence for direct interaction of UGT2B1 with UGT1s was obtained by the
      loss of UGT2B1 adsorption to immunoaffinity column in Gunn rat hepatic
      microsomes, which lack all UGT1 isozymes. When the microsomes were treated with
      the chemical cross-linking reagent 1,6-bis(maleimido)-hexane, a cross-linked
      product with an apparent molecular mass of 120-130 kDa was obtained that
      immunostained with antibodies against UGT1s and UGT2B1, indicating the formation
      of a heterodimer containing one of the UGT1 isozymes and UGT2B1. The effects of
      UGT complex formation on the stimulation of glucuronidation of testosterone and
      uptake of UDP-glucuronic acid (UDP-GlcUA) by UDP-N-acetylglucosamine (UDP-GlcNAc)
      were examined. Alkaline pH-induced dissociation of the complexes was associated
      with the loss of UDP-GlcNAc-dependent stimulation of glucuronidation, suggesting
      that two functional states of UGTs with different kinetic parameters correspond
      to the monomer and oligomer form of UGTs in the membranes. The UDP-GlcNAc
      dependent stimulation of UDP-GlcUA uptake into the microsomal vesicles also was
      affected by the extent of complex formation. These results suggest that complex
      formation of the UGT isozymes affects the UDP-GlcNAc-dependent stimulation of
      glucuronidation via stimulation of UDP-GlcUA uptake.

PMID- 9188716
TI  - Involvement of a flavin iminoquinone methide in the formation of 6-hydroxyflavin
      mononucleotide in trimethylamine dehydrogenase: a rationale for the existence of
      8alpha-methyl and C6-linked covalent flavoproteins.
AB  - In trimethylamine dehydrogenase, substrate is bound in the active site via cation
      pi bonding to three aromatic residues (Tyr-60, Trp-264, and Trp-355). Mutation of
      one of these residues (Trp-355 --> Leu, mutant W355L) influences the chemistry of
      the flavin mononucleotide in the active site, enabling derivatization to 6
      hydroxy-FMN. The W355L mutant is purified as a mixture of deflavo, natural 6-S
      cysteinyl-FMN, and inactive 6-hydroxy-FMN forms, and the enzyme is severely
      compromised in its ability to oxidatively demethylate trimethylamine. Analysis of
      samples of the native and recombinant wild-type trimethylamine dehydrogenases
      also revealed the presence of 6-hydroxy-FMN, but at much reduced levels compared
      with that of the W355L enzyme. Unlike that for a C30A mutant of trimethylamine
      dehydrogenase, addition of substrate to the W355L trimethylamine dehydrogenase is
      not required for the production of 6-hydroxy-FMN. A mechanism is proposed for the
      6-hydroxylation of FMN in trimethylamine dehydrogenase that involves an
      electrophilic flavin iminoquinone methide. The proposed mechanism involving the
      flavin iminoquinone methide could apply to the flavinylation of trimethylamine
      dehydrogenase at the C6 position but also to the flavinylation of enzymes via the
      8alpha position, thus providing a rationale for the evolution of covalent
      flavoproteins in general. Covalent linkage at C6 or the 8alpha-methyl prevents 6
      hydroxylation by direct modification at the C6 atom or by preventing formation of
      the flavin iminoquinone methide, respectively.

PMID- 9188717
TI  - Definition of amino acids sufficient for plasma membrane association of CD45 and
      CD45-associated protein.
AB  - The transmembrane protein tyrosine phosphatase CD45 functions to activate Src
      family member kinase activity in T lymphocytes. The inability to activate
      p56(lck) in CD45-deficient cells results in a higher threshold of signaling
      through the T cell receptor. The lymphoid-specific CD45-associated protein,
      CD45AP, interacts with CD45 through transmembrane interactions. Cells lines and
      mice deficient in CD45 express CD45AP mRNA, yet the protein is poorly expressed,
      indicating that CD45 is required for efficient expression of CD45AP. Pulse-chase
      analysis indicates that CD45 associates with CD45AP within minutes of
      biosynthesis. Cell surface labeling and coimmunoprecipitation demonstrate that
      CD45AP associates with surface-expressed CD45. Therefore, CD45AP is localized to
      the plasma membrane. To further characterize this interaction, chimeric proteins
      containing mutations in CD45 transmembrane regions were expressed, and their
      ability to associate with CD45AP was determined. Alanine-scan mutations of the
      CD45 transmembrane region demonstrate that no single amino acid is essential for
      the interaction with CD45AP. However, the expression of chimeric transmembrane
      regions indicates that a minimum of three and a maximum of eight amino acids in
      this region are sufficient to allow interaction with CD45AP.

PMID- 9188718
TI  - The mannose-binding protein A region of glutamic acid185-alanine221 can
      functionally replace the surfactant protein A region of glutamic acid195
      phenylalanine228 without loss of interaction with lipids and alveolar type II
      cells.
AB  - Pulmonary surfactant protein A (SP-A) is a C-type lectin that regulates the
      uptake and secretion of surfactant lipids by alveolar type II cells and binds
      dipalmitoylphosphatidylcholine (DPPC) and galactosylceramide (GalCer). We
      isolated mannose-binding protein A (MBP-A) from rat sera, which is structurally
      analogous to SP-A, and examined if it was functionally equivalent to SP-A. We
      found that MBP-A did not possess the ability to interact with lipids and type II
      cells. The purpose of this study was to investigate the SP-A region involved in
      binding lipids and interacting with type II cells by using chimeric proteins with
      MBP-A. Chimeras AM1, AM2, and AM3 were constructed with SP-A/MBP splice junctions
      at Cys218/Gln210, Lys203/Cys195, and Gly194/Glu185, respectively. All of the
      chimeras bound DPPC and GalCer with activity comparable to recombinant SP-A. The
      three chimeras retained the ability to induce phospholipid vesicle aggregation
      and augment lipid uptake by type II cells, albeit to a lesser extent than wild
      type SP-A. The chimeras inhibited lipid secretion from type II cells with an IC50
      of 0.5 microg/mL and competed effectively for SP-A receptor binding. In addition
      all these chimeras contained the epitope for monoclonal antibody 1D6, which
      blocks specific SP-A function. From these results, we conclude that the MBP-A
      region of Glu185-Ala221 can functionally replace the homologous SP-A region of
      Glu195-Phe228 without loss of interaction with lipids and type II cells.

PMID- 9188719
TI  - The stoichiometry of G alpha(s) palmitoylation in its basal and activated states.
AB  - Palmitoylation is the dynamic modification of proteins by the addition of
      palmitate to cysteine residues. The alpha subunits of heterotrimeric G proteins
      undergo palmitoylation on their amino terminus, and activation of alpha(s)
      accelerates its palmitate turnover. In previous studies, palmitoylation was
      assessed by incorporation or turnover of [3H]palmitate. These studies did not
      determine the fraction of alpha(s) that is palmitoylated because the specific
      activity of [3H]palmitoyl-CoA within cells is indeterminate. We developed an HPLC
      method to determine the fraction of alpha(s) that was palmitoylated in the basal
      and activated states. COS and S49 cells were radiolabeled with [35S]methionine,
      and alpha(s) was immunoprecipitated from the particulate fraction. The
      immunoprecipitated proteins were separated by reverse phase HPLC into two peaks
      that were determined to contain the modified and unmodified forms of alpha(s).
      Approximately 77% of the endogenous alpha(s) in COS cells and 70% in S49 lymphoma
      cells were palmitoylated. The fraction of alpha(s) that was modified did not
      change after treatment with isoproterenol, a beta-adrenergic receptor agonist
      that causes turnover of palmitate on alpha(s). These results suggest that
      receptor activation of alpha(s) caused a rapid turnover of palmitate to maintain
      most of alpha(s) in its palmitoylated form.

PMID- 9188720
TI  - Physical dissection of the structural elements responsible for regulatory
      properties and intersubunit interactions of protein kinase CK2 beta-subunit.
AB  - The noncatalytic beta-subunit of protein kinase CK2 has been shown to display
      various and in some respects antagonistic effects on the catalytic alpha-subunit
      [Boldyreff et al. (1993) Biochemistry 32, 12672-12677; Meggio et al. (1994)
      Biochemistry 33, 4336-4342]. We have now examined the ability of peptides
      encompassing the N- and C-terminal regions of the beta-subunit (beta[1-77] and
      beta[155-215]) to mimic the functions of the whole-length beta-subunit. Peptide
      beta[155-215] possesses only the positive features of the beta-subunit in that it
      prevents thermal inactivation and stimulates basal activity of the alpha-subunit,
      while it does not inhibit but rather stimulates calmodulin phosphorylation. In
      sharp contrast, peptide beta[1-77] neither protects the alpha-subunit nor
      stimulates its basal activity, while acting as a powerful and specific inhibitor
      of calmodulin phosphorylation. Peptide beta[155-215], but not peptide beta[1-77],
      stably interacts with alpha-subunit and also displays remarkable self-associating
      properties. A shorter derivative of beta[155-215], beta[170-215], displaying
      weaker stimulatory properties fails to stably interact with the alpha-subunit and
      to give rise to dimeric/multimeric forms. These data show that the elements
      responsible for the negative regulation are concentrated in the N-terminal moiety
      of the beta-subunit, whereas the C-terminal region retains the beneficial
      properties of the beta-subunit and is capable of self-association and binding of
      the alpha-subunit. Residues between 155 and 170 are necessary for the latter
      functions.

PMID- 9188721
TI  - Calcium-binding mechanism of human nonerythroid alpha-spectrin EF-structures.
AB  - We have used circular dichroism and 1H- and 15N-NMR spectroscopy to investigate
      calcium binding to the two EF-hands of human nonerythroid or alphaII-spectrin.
      Comparison of the 1H-NMR spectra from the peptide containing both EF-hands to the
      peptides containing the single EF-I and EF-II structures showed that both the
      structural and calcium-binding properties are significantly different. Further
      studies of the 121 amino acid peptide containing both EF-hands using circular
      dichroism and NMR showed that the binding of calcium ions induces conformational
      changes. To investigate the calcium-binding mechanism, the chemical shifts
      changes were recorded using multidimensional NMR spectroscopy during calcium
      titration. A total of 25 titration curves were obtained, each corresponding to
      the chemical shift changes of individual amino acid residues. The shapes of these
      titration curves were either hyperbolic or sigmoidal. Using factor analysis, two
      functions were extracted, one hyperbolic and one sigmoidal, which accounted for
      nearly all information present in the titration curves. By fitting the two
      functions to binding curves based on different binding models, we found that the
      binding mechanism is best described as sequential. Since the sigmoidal type was
      more pronounced in the titration curves corresponding to residues from the first
      EF-hand, we suggest that calcium binding to the first EF-hand is described by the
      sigmoidal function, and that the hyperbolic function describes calcium binding to
      the second EF-hand. Therefore, is seems likely that the second EF-hand must
      contain bound calcium before the first EF-hand can bind.

PMID- 9188722
TI  - 1,2,3-Thiadiazole: a novel heterocyclic heme ligand for the design of cytochrome
      P450 inhibitors.
AB  - The 1,2,3-thiadiazole heterocycle has been explored as a heme ligand and
      mechanism-based inactivator for the design of cytochrome P450 inhibitors. One 4,5
      fused bicyclic and three 4,5-disubstituted monocyclic 1,2,3-thiadiazoles have
      been examined for their spectral interactions, inhibition, mechanism-based
      inactivation, and oxidation products by the versatile microsomal P450s 2B4, 2E1,
      and 1A2. The compounds generally show heteroatom coordination to the heme iron;
      however, the binding mode is influenced by the architecture of the active site.
      For example, 4,5-diphenyl-1,2,3-thiadiazole shows type I and type II difference
      spectra with P450s 2B4 and 2E1, respectively, and no spectral perturbation with
      P450 1A2. Except for the fused bicyclic compound, the spectral dissociation
      constants are in the 2-50 microM range. The effectiveness as an inhibitor depends
      on the substituents at the 4- and 5- positions and on the P450 examined.
      Inhibition of the P450-catalyzed 1-phenylethanol oxidation to acetophenone by the
      thiadiazoles does not correlate with either the type of binding spectra or the
      spectral dissociation constants of the compounds. P450s 2E1 and 2B4 are
      inactivated by the 4,5-fused bicyclic 1,2,3-thiadiazole in a mechanism-based
      manner. Inactivation of the P450 correlates with loss in absorbance at 450 nm for
      the ferrous-CO complex. The monocyclic 1,2,3-thiadiazoles do not inactivate any
      of the P450s examined. The 1,2,3-thiadiazole ring is oxidized by the P450 system.
      Oxidation of the monocyclic compounds results in extrusion of the three
      heteroatoms and formation of the corresponding acetylenes, whereas oxidation of
      the fused bicyclic compound does not yield an acetylenic product.

PMID- 9188723
TI  - Structural and kinetic investigations on the 15-21 and 42-45 loops of muscle
      acylphosphatase: evidence for their involvement in enzyme catalysis and
      conformational stabilization.
AB  - The structural and catalytic importance of the 15-21 and 42-45 loop residues of
      the acylphosphatase muscular isoenzyme has been investigated by oligonucleotide
      directed mutagenesis. Seven mutants involving conserved residues of the two loops
      have been prepared and characterized for structural, kinetic, and stability
      features by using different spectroscopic techniques and compared to the wild
      type enzyme. The results are discussed in light of the crystal structure of the
      highly homologous common type acylphosphatase [Thunnissen et al. (1997) Structure
      5, 69-79]. A differential role of the two loops has emerged: the 15-21 and the 42
      45 loops appear mainly involved in active site formation and enzyme structural
      stabilization, respectively. These conclusions are supported by a strong
      impairment of the catalytic efficiency, in terms of enzymatic activity and
      substrate binding capability, for most of the 15-21 loop mutants. In particular,
      the Gly15Ala mutant is completely inactive and displays a native-like overall
      fold, indicating that the correct geometry of the 15-21 loop is an essential
      requisite for optimal enzymatic catalysis. Instead, the Gly45Ala mutant, though
      revealing unchanged catalytic properties, shows a considerably reduced
      conformational stability, as judged by circular dichroism and 1H NMR
      spectroscopy. This finding confirms previous results relative to Thr42 and Thr46
      residues [Taddei et al. (1996) Biochemistry 35, 7077-7083] underlining the
      structural importance of the 42-45 loop as a linker for the two beta alpha beta
      units constituting the overall enzyme structure.

PMID- 9188724
TI  - Sea urchin hatching enzyme (envelysin): cDNA cloning and deprivation of protein
      substrate specificity by autolytic degradation.
AB  - The hatching enzyme (envelysin) of the sea urchin Hemicentrotus pulcherrimus was
      purified from the medium of hatched blastulae. By cDNA cloning its deduced amino
      acid sequence and molecular architecture were revealed. The 591-residue precursor
      with calculated Mr of 66,123 consists of an 18-residue signal sequence, a 151
      residue propeptide, and a 422-residue mature enzyme with N-terminal catalytic and
      C-terminal hemopexin-like domains. As compared with that of Paracentrotus
      lividus, its amino acid sequence is 69% identical and 10% similar. They share
      typical structural features with the mammalian MMP gene family members: cysteine
      switch, zinc-binding signature, methionine-turn, Cys residues near both ends of
      hemopexin-like domain, etc. However, its propeptide has a 70-residue extra
      sequence with an Asp- and Glu-rich stretch, supposedly involved in the proenzyme
      activation by binding Ca2+ ions in seawater. The hinge region is also longer than
      those of most MMPs, with an extra sequence rich in Thr and Arg residues. Mature
      50K enzyme is highly susceptible to autolytic cleavage at Gln(503)-Leu(504),
      producing the 38K form retaining catalytic activity and substrate specificity
      against fertilization envelope. The 38K form and 15K fragment were coeluted from
      a gel-filtration column, suggesting that these two fragments are disulfide
      bridged and that the tertiary structure is not much deviated. The 38K form
      further autolyzed to 32K form by cleaving Tyr(450)-Tyr(451) bond with the loss of
      protein-substrate specificity, retaining only nonspecific protease activity.
      Thus, the autolytic release of 2/3 of the C-terminal domain reduced the highly
      specific enzyme to a common nonspecific protease, implying that the size and
      structure of almost the entire hemopexin-like domain is essential for the protein
      substrate specificity. Moreover, autolytic degradation of envelysins from the two
      species follow quite different pathways despite their high homology in structure.
      The 38K and 32K forms were inhibited by bovine TIMP-1 with different IC50 values,
      indicating that its inhibitory activity depends on the extent of the interaction
      with the C-terminal domain of the enzyme.

PMID- 9188725
TI  - Phosphoinositide binding specificity among phospholipase C isozymes as determined
      by photo-cross-linking to novel substrate and product analogs.
AB  - We tested for the presence of high-affinity phosphatidylinositol 4,5-bisphosphate
      [PI(4,5)P2] and PI(3,4,5)P3 binding sites in four phospholipase C (PLC) isozymes
      (delta1, beta1, beta2, and beta3), by probing these proteins with analogs of
      inositol phosphates, D-Ins(1,4,5)P3, D-Ins(1,3,4,5)P4, and InsP6, and
      polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3, which contain a photoactivatable
      benzoyldihydrocinnamide moiety. Only PLC-delta1 was specifically radiolabeled.
      More than 90% of the label was found in tryptic and chymotryptic fragments which
      reacted with antisera against the pleckstrin homology (PH) domain, whereas less
      than 5% was recovered in fragments that encompassed the catalytic core. In
      separate experiments, the isolated delta1-PH domain was also specifically
      labeled. Equilibrium binding of D-Ins(1,4,5)P3 to PLC-delta1 indicated the
      presence of a single, high-affinity binding site; binding of D-Ins(1,4,5)P3 to
      PLC-beta1, -beta2, or -beta3 was not detected. The catalytic activity of PLC
      delta1 was inhibited by the product D-Ins(1,4,5)P3, whereas no inhibition of PLC
      beta1, -beta2, or -beta3 activity was observed. These results demonstrate that
      the PH domain is the sole high-affinity PI(4,5)P2 binding site of PLC-delta1 and
      that a similar site is not present in PLC-beta1, -beta2, or -beta3. The data are
      consistent with the idea that the PH domain of PLC-delta1, but not the beta
      isozymes, directs the catalytic core to membranes enriched in PI(4,5)P2 and is
      subject to product inhibition.

PMID- 9188726
TI  - Multiple steroidogenic factor 1 binding elements in the human steroidogenic acute
      regulatory protein gene 5'-flanking region are required for maximal promoter
      activity and cyclic AMP responsiveness.
AB  - A proximal element from the human StAR gene promoter, containing the sequence (
      105)TATCCTTGAC(-95), was shown to confer responsiveness to 8-Br-cAMP in the
      presence of steroidogenic factor 1 (SF-1) when placed behind a minimal thymidine
      kinase promoter or an SV40 promoter and transfected into BeWo cells which
      normally lack StAR and SF-1. This element was also transactivated by SF-1 in a
      yeast one-hybrid system. The -105 to -95 sequence was protected by SF-1 in
      footprint analysis and a double-stranded oligonucleotide containing the element
      bound SF-1 specifically in electrophoretic mobility shift assays. Another SF-1
      binding sequence 35 bp upstream of the transcription start site ((-42)CAGCCTTC(
      35)) was identified in the DNase 1 footprint analysis and, when mutated, markedly
      reduced SF-1-dependent and 8-Br-cAMP-stimulated StAR promoter activity in BeWo
      cells. The two proximal SF-1 response elements were shown to be critical for StAR
      promoter function in human granulosalutein cells, which express SF-1 and respond
      to cAMP with increased transcription of the StAR gene. Mutation of either element
      substantially reduced basal and forskolin-stimulated promoter activity, although
      mutation of the -105 to -95 element had more pronounced effects. Mutation of a
      third, more distal, SF-1-binding site at -926 to -918 also reduced basal but not
      forskolin-stimulated promoter activity in the granulosa-lutein cells. These
      findings demonstrate that multiple SF-1 response elements are required for
      maximal StAR promoter activity and regulation by cAMP.

PMID- 9188727
TI  - Importance of the C-terminal helix to the stability and enzymatic activity of
      Escherichia coli ribonuclease H.
AB  - The ribonuclease H (RNase H) family of enzymes selectively degrades the RNA
      strand of RNA-DNA hybrids. This activity is essential for retroviruses such as
      HIV and resides in a domain of the larger reverse transcriptase molecule. RNase H
      from Escherichia coli is the best-characterized member of the family and serves
      as a model for structure/function studies. Despite having almost identical alpha
      + beta folds, the isolated domain from HIV is inactive and much less stable than
      the E. coli homolog. The HIV domain also shows increased disorder in its C
      terminal regions (E-helix and His-containing loop). We investigated the
      importance of this region by studying a variant of E. coli RNase H lacking these
      elements (RNHdeltaE). Despite the elimination of 33 of 155 residues (including a
      complete helix), this C-terminal deletion mutant folds cooperatively as a
      subdomain. Surprisingly, this protein lacking residues near the active site
      retains weak Mn2+-dependent activity. A peptide corresponding to the deleted E
      helix is helical in isolation and stimulates the activity of the deletion mutant
      in vitro. These results have implications for the catalytic mechanism of RNase H
      and drug design targeted to HIV reverse transcriptase.

PMID- 9188728
TI  - Evaluation of the kinetic mechanism of Escherichia coli uridine diphosphate-N
      acetylmuramate:L-alanine ligase.
AB  - Initial velocity methods were used to probe the kinetic mechanism of Escherichia
      coli uridine diphosphate-N-acetylmuramate:L-alanine ligase (UNAM:L-Ala ligase).
      When the activity (in the forward direction) versus substrate concentration data
      were plotted in double-reciprocal form, all line patterns were intersecting. The
      best fit of these data was to the equation for an ordered mechanism with the
      following parameters: k(cat), 1000 +/- 100 min(-1); Kma, 210 +/- 40 microM; Kmb,
      84 +/- 20 microM; Kmc, 70 +/- 15 microM; Kia, 180 +/- 50 microM; Kib, 68 +/- 24
      microM. Initial velocity line patterns were also determined when the
      concentration of one substrate was varied at different fixed concentrations of a
      second substrate while the third substrate was held at a concentration more than
      100 times its Km value. Reciprocal plots of data collected with either ATP or L
      alanine present at more than 100 times their Km values resulted in intersecting
      line patterns. Data collected with UNAM present at 100 times its Km value gave a
      set of parallel lines. These data are consistent with UNAM binding as the second
      substrate in an ordered mechanism. ADP, uridine diphosphate-N-acetylmuramoyl-L
      alanine (UNAMA), and phosphate were tested as product inhibitors versus
      substrates. None of the products were competitive inhibitors versus L-alanine or
      UNAM, while the only observed competitive inhibition was ADP versus ATP. These
      results are consistent with an ordered kinetic mechanism wherein ATP binds first,
      UNAM binds second, and ADP is the last product released. Rapid quench experiments
      were performed in the presence of all three substrates or in the presence of ATP
      and UNAM. The production of acid-labile phosphate as a function of time is
      characterized by a burst phase followed by a slower linear phase with the rate
      close to k(cat) in the presence of all three substrates. Only a burst phase was
      observed for the time course of the reaction in the presence of ATP and UNAM. In
      both cases, the burst rate was identical. These observations are consistent with
      L-alanine being the third substrate to bind in a sequential mechanism involving a
      putative acyl-phosphate intermediate.

PMID- 9188730
TI  - Comment to Daura, X., et al., Proteins 25:89-103, 1996.

PMID- 9188731
TI  - Loss of translational entropy in binding, folding, and catalysis.
AB  - There is a loss of translational entropy associated with the formation of a
      complex between two molecules in solution. Estimation of this contribution is
      essential for understanding binding, protein-protein association, and catalysis.
      Based on the cell model of liquids, it is possible to estimate the loss of
      translational entropy in all these cases. The resulting formulas are
      straightforward, and the calculations are easy to perform. Comparison of the
      results with experimental data suggests that the proposed method provides
      estimates that are much more accurate than those obtained with existing methods.

PMID- 9188729
TI  - Thermodynamics of oligoarginines binding to RNA and DNA.
AB  - We have examined the equilibrium binding of a series of synthetic oligoarginines
      (net charge z = +2 to +6) containing tryptophan to poly(U), poly(A), poly(C),
      poly(I), and double-stranded (ds) DNA. Equilibrium association constants, K(obs),
      measured by monitoring tryptophan fluorescence quenching, were examined as
      functions of monovalent salt (MX) concentration and type, as well as temperature,
      from which deltaG(standard)obs, deltaH(obs), and deltaS(standard)obs were
      determined. For each peptide, K(obs) decreases with increasing [K+], and the
      magnitude of the dependence of K(obs) on [K+], delta log K(obs)/delta log[K+],
      increases with increasing net peptide charge. In fact, the values of delta log
      K(obs)/delta log[K+] are equivalent for oligolysines and oligoarginines
      possessing the same net positive charge. However, the values of K(obs) are
      systematically greater for oligoarginines binding to all polynucleotides, when
      compared to oligolysines with the same net charge. The origin of this difference
      is entirely enthalpic, with deltaH(obs), determined from van't Hoff analysis,
      being more exothermic for oligoarginine binding. The values of deltaH(obs) are
      also independent of [K+]; therefore, the salt concentration dependence of
      deltaG(standard)obs is entirely entropic in origin, reflecting the release of
      cations from the nucleic acid upon complex formation. These results suggest that
      hydrogen bonding of arginine to the phosphate backbone of the nucleic acids
      contributes to the increased stability of these complexes.

PMID- 9188732
TI  - NMR studies on the flexibility of nucleoside diphosphate kinase.
AB  - Human NDP kinase B, product of the nm23-H2 gene, binds DNA. It has been suggested
      that a helix hairpin on the protein surface, part of the nucleotide substrate
      binding site, could accommodate DNA binding by swinging away. The presence of
      flexible regions was therefore investigated by 1H NMR dynamic filtering. Although
      TOCSY peaks could be assigned to five residues at the N terminus of Dictyostelium
      NDP kinase, no flexible region was detected in the human enzyme. These data favor
      the idea that the protein offers different binding sites to mono- and
      polynucleotides.

PMID- 9188733
TI  - The kinetics of protein-protein recognition.
AB  - We examine a simple kinetic model for association that incorporates the basic
      features of protein-protein recognition within the rigid body approximation, that
      is, when no large conformation change occurs. Association starts with random
      collision at the rate k(coll) predicted by the Einstein-Smoluchowski equation.
      This creates an encounter pair that can evolve into a stable complex if and only
      if the two molecules are correctly oriented and positioned, which has a
      probability p(r). In the absence of long-range interactions, the bimolecular rate
      of association is p(r) k(coll). Long-range electrostatic interactions affect both
      k(coll) and p(r). The collision rate is multiplied by q(t), a factor larger than
      1 when the molecules carry net charges of opposite sign as coulombic attraction
      makes collisions more frequent, and less than 1 in the opposite case. The
      probability p(r) is multiplied by a factor q(r) that represents the steering
      effect of electric dipoles, which preorient the molecules before they collide.
      The model is applied to experimental data obtained by Schreiber and Fersht (Nat.
      Struct. Biol. 3:427-431, 1996) on the kinetics of barnase-barstar association.
      When long-range electrostatic interactions are fully screened or mutated away,
      q(t)q(r) approximately 1, and the observed rate of productive collision is p(r)
      k(coll) approximately 10(5) M(-1) x s(-1). Under these conditions, p(r)
      approximately 1.5 x 10(-5) is determined by geometric constraints corresponding
      to a loss of rotational freedom. Its value is compatible with computer docking
      simulations and implies a rotational entropy loss deltaS(rot) approximately 22
      e.u. in the transition state. At low ionic strength, long-range electrostatic
      interactions accelerate barnase-barstar association by a factor q(t)q(r) of up to
      10(5) as favorable charge-charge and charge-dipole interactions work together to
      make it much faster than free diffusion would allow.

PMID- 9188734
TI  - Automated docking of glucosyl disaccharides in the glucoamylase active site.
AB  - To better understand the molecular basis of glucomylase selectivity, low-energy
      conformers of glucosyl disaccharides obtained from relaxed-residue conformational
      mapping were flexibly docked into the glucoamylase active site using AutoDock
      2.2. This procedure ensures that significant conformational space is searched and
      can produce bound structures comparable to those obtained by protein
      crystallography. alpha-Linked glucosyl disaccharides except alpha,alpha-trehalose
      dock easily into the active site while exclusively beta-linked disaccharides do
      not, explaining why only the former are glucoamylase substrates. The optimized
      docking modes are similar at the nonreducing end of the different substrates.
      Individual atomic energies of intermolecular interaction allow the definite
      identification of key hydroxyl groups for each substrate. This approach confirmed
      the versatility of the second subsite of the glucoamylase active site in binding
      different substrates.

PMID- 9188735
TI  - Electrostatics of proteins: description in terms of two dielectric constants
      simultaneously.
AB  - In the semi-continuum treatment of the energetics of charge formation (or
      transfer) inside a protein, two components of the energy are inevitably present:
      the energy of interaction of the ion with the pre-existing intraprotein electric
      field, and the energy due to polarization of the medium by the newly formed
      charge. The pre-existing field is set up by charges (partial or full) of the
      protein atoms fixed in a definite structure. The calculation of this field
      involves only the electronic polarization (the optical dielectric constant
      epsilon(o)) of the protein because the polarization due to shifts of heavy atoms
      has already been accounted for by their equilibrium coordinates. At the same
      time, the aqueous surroundings should be described by the static constant
      epsilon(sw), as the positions of water molecules are not fixed. The formation of
      a new charge, absent in the equilibrium X-ray structure, results in shifts of
      electrons and polar atoms, i.e., it involves all kinds of medium polarization
      described by the static dielectric constant of protein epsilon(s). Thus, in
      calculations of the total energy, two different dielectric constants of the
      protein are operative simultaneously. This differs from a widely used algorithm
      employing one effective dielectric constant for both components of the ion's
      energy.

PMID- 9188737
TI  - Roughness of the globular protein surface: analysis of high resolution X-ray
      data.
AB  - In an earlier publication [Serdyuk, I.N. et al., Biofizika, in press, 1997] we
      demonstrated that the asymmetry extent of globular proteins does not change with
      increasing their sizes, and the observed nontrivial dependence of the protein
      accessible surface area on the molecular mass [Miller, S., J. Mol. Biol. 196:641
      656, 1987] (A(s) - M dependence) is a reflection of the protein surface relief
      peculiarities. To clarify these peculiarities, an analysis of the molecular
      surface on the basis of high-resolution x-ray data has been done for 25 globular
      proteins not containing prosthetic groups. The procedure was based on studying
      the dependence of the minimal number (N) of probe bodies (here cubes) covering
      the entire protein surface, both on their size (N - R dependence) and on the
      value of dry protein volume (N - V dependence). Two levels of protein surface
      organization have been detected by molecular surface analysis. On the micro scale
      (2-7 A), the surface is characterized by a D = 2.1 fractal dimension which is
      intrinsic to surfaces with weak deformations and reflects the local atomic group
      packing. On the macro scale, large-scale surface defects are revealed that are
      interpreted as the result of secondary structure elements packing. A simple model
      of protein surface representation reflecting large-scale irregularities has been
      proposed.

PMID- 9188736
TI  - Role of electrostatics at the catalytic metal binding site in xylose isomerase
      action: Ca(2+)-inhibition and metal competence in the double mutant D254E/D256E.
AB  - The catalytic metal binding site of xylose isomerase from Arthrobacter B3728 was
      modified by protein engineering to diminish the inhibitory effect of Ca2+ and to
      study the competence of metals on catalysis. To exclude Ca2+ from Site 2 a double
      mutant D254E/D256E was designed with reduced space available for binding. In
      order to elucidate structural consequences of the mutation the binary complex of
      the mutant with Mg2+ as well as ternary complexes with bivalent metal ions and
      the open-chain inhibitor xylitol were crystallized for x-ray studies. We
      determined the crystal structures of the ternary complexes containing Mg2+, Mn2+,
      and Ca2+ at 2.2 to 2.5 A resolutions, and refined them to R factors of 16.3,
      16.6, and 19.1, respectively. We found that all metals are liganded by both
      engineered glutamates as well as by atoms O1 and O2 of the inhibitor. The
      similarity of the coordination of Ca2+ to that of the cofactors as well as
      results with Be2+ weaken the assumption that geometry differences should account
      for the catalytic noncompetence of this ion. Kinetic results of the D254E/D256E
      mutant enzyme showed that the significant decrease in Ca2+ inhibition was
      accompanied by a similar reduction in the enzymatic activity. Qualitative
      argumentation, based on the protein electrostatic potential, indicates that the
      proximity of the negative side chains to the substrate significantly reduces the
      electrostatic stabilization of the transition state. Furthermore, due to the
      smaller size of the catalytic metal site, no water molecule, coordinating the
      metal, could be observed in ternary complexes of the double mutant. Consequently,
      the proton shuttle step in the overall mechanism should differ from that in the
      wild type. These effects can account for the observed decrease in catalytic
      efficiency of the D254E/D256E mutant enzyme.

PMID- 9188738
TI  - Ligand-based protein alignment and isozyme specificity of glutathione S
      transferase inhibitors.
AB  - Glutathione S-transferases (GST, E.C.2.5.1.18) comprise a family of
      detoxification enzymes. Elevated levels of specific GST isozymes in tumor cells
      are thought responsible for resistance to chemotherapeutics, which renders
      selective GST inhibitors potentially useful pharmaceutical agents. We discuss the
      development of a structure activity model that rationalizes the isozyme
      selectivity observed in a series of 12 glutathione (GSH) analogues. Enzymatic
      activity data was determined for human P1-1, A1-1, and M2-2 isozymes, and these
      data were then considered in light of structural features of these three GST
      proteins. A survey of all GST structures in the PDB revealed that GSH binds to
      these proteins in a single "bioactive" conformation. To focus on differences
      between binding sites, we exploited our finding of a common GSH conformation and
      aligned the GST x-ray structures using bound ligands rather than the backbones of
      the different proteins. Once aligned, binding site lipophilicity and
      electrostatic potentials were computed, visualized, and compared. Docking and
      energy minimization exercises provided additional refinements to a model of
      selectivity developed initially by visual analysis. Our results suggest that
      binding site shape and lipophilic character are key determinants of GST isozyme
      selectivity for close GSH analogues.

PMID- 9188739
TI  - Knowledge-based modeling of a bacterial dichloromethane dehalogenase.
AB  - A three-dimensional structural model of the dichloromethane dehalogenase (DCMD)
      from Methylophilus sp. DM11 is constructed based on sequence similarities to the
      glutathione S-transferases (GSTs). To maximize sequence identity and minimize
      gaps in the alignment, a hybrid approach is used that takes advantage of the
      increased homology found between DM11 and domain I of the sheep blowfly theta
      class GST (residues 1-79) and domain II of the human alpha class GST (residues 81
      222). The resulting structure has C alpha root mean square deviations of 1.16 A
      in domain I and 1.83 A in domain II from the template GSTs, which compare well to
      those seen in other GST inter-class comparisons. The model is further applied to
      explore the structural basis for substrate binding and catalysis. A conserved
      network of hydrogen bonds is described that binds glutathione to the G site,
      placing the thiol group in a suitable location for nucleophilic attack of
      dichloromethane. A mechanism is proposed that involves activation through a
      hydrogen bond interaction between Ser12 and glutathione, similar to that found in
      the theta-GSTs. The model also demonstrates how aromatic residues in the
      hydrophobic site (H site) could play a role in promoting catalysis: His116 and
      Trp117 are ideally situated to accept a growing negative charge on a chlorine of
      dichloromethane, stabilizing displacement. This scheme is consistent with
      experimental results of single-point mutations and comparisons with other GST
      structures and mechanisms.

PMID- 9188740
TI  - Studies of the unfolding of an unstable mutant of staphylococcal nuclease:
      evidence for low temperature unfolding and compactness of the high temperature
      unfolded state.
AB  - Fluorescence and circular dichroism data as a function of temperature were
      obtained to characterize the unfolding of nuclease A and two of its less stable
      mutants. These spectroscopic data were obtained with a modified instrument that
      enables the nearly simultaneous detection of both fluorescence and CD data on the
      same sample. A global analysis of these multiple datasets yielded an excellent
      fit of a model that includes a change in the heat capacity change, deltaC(p),
      between the unfolded and native states. This analysis gives a deltaC(p) of 2.2
      kcal/mol/ x K for thermal unfolding of the WT protein and 1.3 and 1.8 kcal/mol/K
      for the two mutants. These deltaC(p) values are consistent with significant
      population of the cold unfolded state at approximately 0 degrees C. Independent
      evidence for the existence of a cold unfolded state is the observation of a
      separately migrating peak in size exclusion chromatography. The new
      chromatographic peak is seen near 0 degrees C, has a partition coefficient
      corresponding to a larger hydrodynamic radius, and shows a red-shifted
      fluorescence spectrum, as compared to the native protein. Data also indicate that
      the high-temperature unfolded form of mutant nuclease is relatively compact. Size
      exclusion chromatography shows the high temperature unfolded form to have a
      hydrodynamic radius that is larger than that for the native form, but smaller
      than that for the urea or pH-induced unfolded forms. Addition of chemical
      denaturants to the high-temperature unfolded form causes a further unfolding of
      the protein, as indicated by an increase in the apparent hydrodynamic radius and
      a decrease in the rotational correlation time for Trp140 (as determined by
      fluorescence anisotropy decay measurements).

PMID- 9188741
TI  - Structural trees for protein superfamilies.
AB  - Structural trees for large protein superfamilies, such as beta proteins with the
      aligned beta sheet packing, beta proteins with the orthogonal packing of alpha
      helices, two-layer and three-layer alpha/beta proteins, have been constructed.
      The structural motifs having unique overall folds and a unique handedness are
      taken as root structures of the trees. The larger protein structures of each
      superfamily are obtained by a stepwise addition of alpha helices and/or beta
      strands to the corresponding root motif, taking into account a restricted set of
      rules inferred from known principles of the protein structure. Among these rules,
      prohibition of crossing connections, attention to handedness and compactness, and
      a requirement for alpha helices to be packed in alpha-helical layers and beta
      strands in beta layers are the most important. Proteins and domains whose
      structures can be obtained by stepwise addition of alpha helices and/or beta
      strands to the same root motif can be grouped into one structural class or a
      superfamily. Proteins and domains found within branches of a structural tree can
      be grouped into subclasses or subfamilies. Levels of structural similarity
      between different proteins can easily be observed by visual inspection. Within
      one branch, protein structures having a higher position in the tree include the
      structures located lower. Proteins and domains of different branches have the
      structure located in the branching point as the common fold.

PMID- 9188742
TI  - Structural definition of the C5a C terminus by two-dimensional nuclear magnetic
      resonance spectroscopy.
AB  - The serum glycoprotein C5a, which is derived from the proteolytic cleavage of
      complement protein C5, has been implicated in the pathogenesis of a number of
      inflammatory and allergic conditions. Because C5a induces an inflammatory
      response upon binding to a specific receptor, structural and mutagenesis studies
      were carried out to gain a better understanding of this binding interaction.
      These studies led to the first structural definition of the C terminus of
      recombinant human (rh)-C5a, determined by two-dimensional nuclear magnetic
      resonance (NMR) spectroscopy. Our results show that the C terminus adopts an
      alpha-helical conformation spanning residues 69 to 74, while the core domain
      exists as an antiparallel alpha-helical bundle. This C-terminal helix is
      connected to the core by a short loop that orients Arg 74 adjacent to Arg 62.
      Point mutation analysis had already revealed that residues 62 and 74
      significantly contribute to agonist activity and receptor binding. Correlation of
      the C5a tertiary structure with mutational analyses clarifies the significance of
      the functional and binding properties of Arg 62 and suggests that both Arg 62 and
      Arg 74 interact at the same binding site on the receptor.

PMID- 9188743
TI  - Role of aromatic amino acids in carbohydrate binding of plant lectins: laser
      photo chemically induced dynamic nuclear polarization study of hevein domain
      containing lectins.
AB  - Carbohydrate recognition by lectins often involves the side chains of tyrosine,
      tryptophan, and histidine residues. These moieties are able to produce chemically
      induced dynamic nuclear polarization (CIDNP) signals after laser irradiation in
      the presence of a suitable radical pair-generating dye. Elicitation of such a
      response in proteins implies accessibility of the respective groups to the light
      absorbing dye. In principle, this technique is suitable to monitor surface
      properties of a receptor and the effect of ligand binding if CIDNP-reactive amino
      acids are affected. The application of this method in glycosciences can provide
      insights into the protein-carbohydrate interaction process, as illustrated in
      this initial study. It focuses on a series of N-acetylglucosamine-binding plant
      lectins of increasing structural complexity (hevein, pseudohevein, Urtica dioica
      agglutinin and wheat germ agglutinin and its domain B), for which structural NMR-
      or X-ray crystallographic data permit a decision of the validity of the CIDNP
      method-derived conclusions. On the other hand, the CIDNP data presented in this
      study can be used for a rating of our molecular models of hevein, pseudohevein,
      and domain B obtained by various modeling techniques. Experimentally, the shape
      and intensity of CIDNP signals are determined in the absence and in the presence
      of specific glycoligands. When the carbohydrate ligand is bound, CIDNP signals of
      side chain protons of tyrosine, tryptophan, or histidine residues are altered,
      for example, they are broadened and of reduced intensity or disappear completely.
      In the case of UDA, the appearance of a new tryptophan signal upon ligand binding
      was interpreted as an indication for a conformational change of the corresponding
      indole ring. Therefore, CIDNP represents a suitable tool to study protein
      carbohydrate interactions in solution, complementing methods such as X-ray
      crystallography, high-resolution multidimensional nuclear magnetic resonance,
      transferred nuclear Overhauser effect experiments, and molecular modeling.

PMID- 9188744
TI  - Expression, crystallization and preliminary X-ray diffraction study of FtsY, the
      docking protein of the signal recognition particle of E. coli.
AB  - FtsY is the docking protein or SR alpha homologue in E. coli. It is involved in
      targeting secretory proteins to the cytoplasmic membrane by interacting with the
      signal recognition particle, controlled by guanosine 5'-triphosphate. Two
      different constructs have been used in crystallization studies: the full-length
      protein and a truncated fragment with a his-tag at the C terminus. Only the
      second construct resulted in crystals suitable for x-ray diffraction. The
      crystals belong to the monoclinic space group P2(1) with cell dimensions a =
      32.20 A, b = 79.57 A, c = 59.21 A, and beta = 94.45, and contain one molecule per
      asymmetric unit. At cryogenic temperatures the crystals diffract to a resolution
      limit of 2.5 A by using a rotating anode, and beyond 1.8 A by using synchrotron
      radiation.

PMID- 9188745
TI  - Preparation and crystallization of a cross-linked complex of bovine adrenodoxin
      and adrenodoxin reductase.
AB  - Bovine adrenodoxin was cross-linked to adrenodoxin reductase with 1-ethyl-3-(3
      dimethyl-aminopropyl) carbodiimide. Mass spectrometry showed the reaction product
      to be a 1:1 complex of the two proteins with M(r) = 64,790 +/- 50. The cross
      linked complex showed cytochrome c reductase activity and could be crystallized
      by hanging-drop vapor diffusion. Crystals of the adrenodoxin-adrenodoxin
      reductase complex are hexagonal, space group P6(1)22 or P6(5)22, with a = 93.26 A
      and c = 612.20 A and diffract to 2.9 A resolution at 100 K. Assuming two cross
      linked complexes per asymmetric unit yields a reasonable V(M) of 2.97 A3/Da.

PMID- 9188746
TI  - Crystallization and preliminary X-ray diffraction data of two different human low
      density lipoprotein (LDL) subfractions.
AB  - Human LDL subfractions LDL-2 (d = 1.031-1.034 g/ml) and LDL-5 (d = 1.040-1.044
      g/ml) were crystallized in two different crystal forms by using polyethylene
      glycol as a precipitant. Both fractions were from one donor. Crystals of LDL-5
      were yellow, hexagonal, and showed no dichroism. Crystals of LDL-2 were of the
      same color, had a rodlike shape with notches at both ends, and were highly
      dichroitic. LDL-2 crystals diffracted to a resolution of 29 A by using
      synchrotron radiation. Indexing in P1 resulted in preliminary parameters for the
      reduced cell of a = 171 A, b = 438 A, c = 519 A, alpha = 102 degrees, beta = 99
      degrees, gamma = 91. These dimensions are consistent with the size of LDL
      particles. Using Fourier transform infrared spectroscopy (FTIR) and agarose gel
      electrophoresis, we could further confirm that the crystals consist of LDL. The
      FTIR spectrum showed bands characteristic for lipids and protein. Dissolved
      crystals exhibited a mobility similar to native LDL in agarose gels and could be
      stained with anti-human apolipoprotein B (apoB).

PMID- 9188747
TI  - Purification and crystallization of Pseudomonas aeruginosa chloramphenicol
      acetyltransferase.
AB  - A chloramphenicol acetyltransferase from Pseudomonas aeruginosa genomic DNA has
      been overexpressed, refolded, purified, and crystallized. Crystals suitable for a
      three-dimensional x-ray structure determination were obtained from solutions of
      polyethyleneglycol methyl ether 2000 containing NiCl2 at pH 8.5. These crystals
      belong to the cubic space group P4(1/3)32 (a = 154.8 A) and diffract x-rays to
      approximately 3.2 A resolution.

PMID- 9188748
TI  - A conserved cluster of homeodomain binding sites in the mouse Hoxa-4 intron
      functions in Drosophila embryos as an enhancer that is directly regulated by
      Ultrabithorax.
AB  - The evolutionary conservation of the homeodomains suggests that their in vivo DNA
      binding sites may also be conserved between vertebrates and invertebrates. The
      regulatory function of the mouse Hoxa-4 and Hoxb-4 introns were analyzed in
      Drosophila since they both contain a cluster of three homeodomain binding sites,
      the HB1 element, which was also found in the introns of other Hox genes ranging
      from fish to humans as well as in the Ultrabithorax (Ubx) and decapentaplegic
      (dpp) genes of Drosophila. The enhancer of the Hoxa-4 intron was found to respond
      to several homeobox genes activating a lacZ reporter gene in particular cells of
      the epidermis in Drosophila embryos. The enhancer activity was found to be
      similar to previously described autoregulatory elements of Deformed (Dfd), the
      Drosophila homolog of Hoxa-4, but additional expression was observed in more
      posterior segments activated by Ubx and repressed by abdominal-A (abd-A). Point
      mutations in the homeodomain binding sites in HB1 abolished the enhancer
      activity. A second site suppression experiment showed that UBX interacts directly
      with the HB1 element. When the HB1 element in the Hoxa-4 intron was replaced by
      that of the mesodermal enhancer of dpp, which was previously shown to be directly
      controlled by Ubx, Ubx-dependent activation was retained, but repression by abd-A
      was lost. The same result was obtained when the third binding site of HB1 was
      altered, suggesting that this site is responsible for abd-A-dependent repression.
      Finally, deletion of potential cofactor binding sites flanking the HB1 element
      that are also conserved in the medaka, chicken, and mouse genes revealed that
      they are important for enhancer function in Drosophila and that the Dfd-dependent
      and the Ubx-dependent expression requires different sites. The evolutionary and
      functional conservation of the HB1 elements indicates that not only the
      homeodomains but also some of their in vivo binding sites are conserved between
      vertebrates and invertebrates.

PMID- 9188749
TI  - Regulated exocytosis and sequential construction of the extracellular matrix
      surrounding the sea urchin zygote.
AB  - After fertilization most eggs become surrounded by a complex extracellular
      matrix. This study examines those matrix assembly processes that are triggered by
      fertilization of the sea urchin egg. The study uses antibodies that identify five
      different storage compartments in the egg. These compartments release their
      protein contents in a highly regulated fashion to assemble and modify the
      extraembryonic layers. The exocytosis sequence begins with a fertilization wave
      that progresses from the site of sperm entry and elevates the fertilization
      envelope above a water-filled perivitelline space. The immediate surface of the
      zygote then becomes covered by a newly secreted hyaline layer. Prior to
      fertilization some of the antigens are localized to cortical granules. Others are
      found in "basal laminar vesicles" that are released in a wave beginning at about
      30 sec, or roughly at the same time as cortical granule exocytosis. The remaining
      antigens are exocytosed with a rather precise timing, but with a delay of several
      to tens of minutes relative to the first wave of exocytosis. "Apical vesicles,"
      so named because antigens from this class are preferentially exocytosed toward
      the apical cell surface of polarized cells, include antigens that are exocytosed
      beginning at about 5 min postfertilization. The fourth compartment, named
      "echinonectin vesicles" release echinonectin, a protein that is deposited to the
      inner side of the hyaline layer. Surface staining of echinonectin is first
      detected about 10-15 min following sperm contact. Finally, maternal cadherin,
      which is stored in yet a fifth distinct compartment, is not detected on the
      surface until at least 30 min following fertilization. The data are also
      consistent with the notion that the tightly regulated timing of exocytosis
      contributes to the ordered assembly of the hyaline layer and elevation of the
      fertilization envelope. Finally, two of the vesicle classes continue to exocytose
      after the cells become polarized. In polarized cells apical and basal laminar
      antigens are trafficked toward opposite sides of the same cell after passing
      through the same trans-Golgi network-like compartment.

PMID- 9188750
TI  - Muscle sensory innervation patterns in embryonic chick hindlimbs following dorsal
      root ganglion reversal.
AB  - Previous studies suggest that sensory innervation of muscles is patterned by
      motor innervation. Muscle afferent projections mirror motor projections after
      various experimental manipulations and muscle afferents fail to project to muscle
      in the absence of motoneurons. It is not known, however, whether muscle afferents
      are specified with respect to the corresponding motoneurons or target muscles. To
      test this possibility we rotated three to four segments of neural crest in St. 15
      17 chick embryos, leaving motoneurons intact, to reverse the rostrocaudal order
      of dorsal root ganglia (DRGs) T7/LS1-LS3. This caused sensory neurons derived
      from one segmental level to grow into the limb with motor axons from a different
      level. The resulting innervation patterns were assessed at St. 28-37 by injecting
      DiI and DiA into the sartorius and femorotibialis muscles or into the spinal cord
      and DRG. DiI labeling of crest prior to rotation showed that DRGs in the operated
      region were derived primarily from rotated cells. Muscle afferents from rotated
      DRGs grew to muscles in accord with their new rostrocaudal position, together
      with "inappropriate" motor axons from the same segmental level. The segmental
      distribution of sensory neurons innervating each muscle was more widespread in
      embryos operated at older than at younger stages. In contrast, sensory axons
      projected to the appropriate muscles in accord with their embryonic origin when
      segments of the whole neural tube, including motoneurons, were rotated, as
      reported previously. Thus, sensory neurons do not appear to be selectively
      matched with motoneurons or target muscles at stages when the corresponding
      motoneurons have clear identities.

PMID- 9188751
TI  - Induction of leaves directly from leaves in the maize mutant Lax midrib1-O.
AB  - One of the several phenes specified by the maize dominant mutation Lax midrib1-O
      (Lxm1-O on 3L) is the proliferation of leaf "flaps" usually paired around veins
      on the abaxial leaf surface. Using histology and scanning electron microscopy, we
      show these flaps to be authentic leaf structures; in rare instances, complete
      ectopic leaves are found. The first divisions preceding flap emergence occur
      between plastochrons 4 and 7, stages when the course of leaf differentiation is
      well under way. No sign of meristem or any small, densely cytoplasmic primordium
      like cells were seen at the sites of flap initiation. In addition, the sites of
      ectopic leaf initiation do not express KNOX (Knotted-like homeobox) proteins, a
      molecular marker for shoot apical meristem cell identity. Thus, the cells that
      proliferate into ectopic leaves do not arise from a meristem or a primordium. A
      similar phenomenon has been described in several dicots, but in no other
      monocots. The details of flap morphology compared to the morphology of the leaf
      proper suggest a model whereby cells in regions of the leaf proper maintain the
      competence they acquired in the meristem. These cells then respond properly, in a
      regulated manner, to a delayed signal emanating from veins denoting "make the
      organ you are competent to make."

PMID- 9188752
TI  - Involvement of the Bombyx Scr gene in development of the embryonic silk gland.
AB  - Homeotic selector genes determine the identity of each segment and induce the
      differentiation of segment-specific organs. To analyze how the silk glands of the
      lepidopteran, Bombyx mori, develop, we cloned and identified two genes that
      encode the homeodomain and its flanking regions identical to the corresponding
      regions of Deformed and Sex combs reduced. Using in situ hybridization and
      immunohistochemistry, we analyzed the expression patterns of these genes during
      Bombyx embryogenesis. Bombyx Deformed is expressed in the mandibular and
      maxillary segments, whereas expression of Bombyx Sex combs reduced is first
      limited to the labial segment and at later stages extended to the anterior part
      of the prothoracic segment. The expression of Bombyx Sex combs reduced then
      disappears from the invaginating placodes of silk glands where expression of
      Bombyx fork head/SGF-1 follows. In the Nc/Nc mutant embryos, which lack the 3'
      end region of Bombyx Antennapedia, in addition to the expression in the labial
      segment, the Bombyx Sex combs reduced is expressed ectopically in the thoracic
      and abdominal regions, and Bombyx fork head/SGF-1 is also ectopically expressed
      in the T1, T2, and T3 segments, resulting the ectopic induction of the silk gland
      invaginations. These results suggest that Bombyx homeobox genes such as the
      Bombyx Deformed and Sex combs reduced are associated with determination of the
      segment identities and Bombyx Sex combs reduced is involved in the induction of
      silk gland development.

PMID- 9188753
TI  - A heart segmental defect in the anterior-posterior axis of a transgenic mutant
      mouse.
AB  - A recessive lethal insertional mutation on chromosome 13 has been identified in a
      transgenic mouse line that displays a segmental form of cardiac defect along the
      anterior-posterior axis in all homozygous mice identified. The most anterior
      segment (future conus and right ventricle) of the single heart tube fails to
      develop normally and the endocardial cushions in both the conus and the
      atrioventricular regions are missing. Analysis of the beta-galactosidase reporter
      portion of the transgene during embryonic development shows a segmental
      expression of activity primarily in the defective outlet of the primitive heart.
      In addition to expression in the heart tube, hemizygous embryos show transgene
      expression in the chondrogenic regions of first and second branchial arches, the
      appendicular skeleton, and the dermal papillae of the vibrissae. The restricted
      pattern of beta-galactosidase expression in the heart can be disrupted with
      retinoic acid exposure and extended posteriorly along the anterior-posterior axis
      in hemizygous mice. Although cushion mesenchyme fail to form in the homozygous
      mutant, the myocardial and endothelial cells explanted from the mutant
      atrioventricular, but not the conus, are capable of forming mesenchyme in vitro.
      Mice trisomic for chromosome 13 have also been shown to display segmental
      anomalies associated with the anterior primitive outlet segments of the heart.
      Our data show that this insertional mutation identifies a new gene locus, hdf
      (heart defect), on mouse chromosome 13 that may be required for mechanisms that
      initially establish and/or maintain continued development of the anterior limb of
      the developing heart. The hdf mouse mutation also provides a new model system to
      evaluate the molecular requirements of normal endocardial cushion formation and
      the segmental interactions that form the adult heart.

PMID- 9188754
TI  - The ability to organize sperm DNA into functional chromatin is acquired during
      meiotic maturation in murine oocytes.
AB  - Following fertilization of meiotically mature eggs, the chromatin of the sperm
      becomes biochemically and structurally remodeled within the egg cytoplasm.
      Despite the essential role of the paternal genome during embryogenesis, little is
      known of when the activities that regulate this chromatin remodeling appear
      during oogenesis. To determine whether these activities were acquired during
      meiotic maturation, we inseminated maturing oocytes of mice shortly after
      germinal vesicle breakdown. As previously shown, insemination at this stage did
      not activate the maturing oocytes, which became arrested at metaphase II.
      Immunofluorescent analysis revealed that at 1 hr postinsemination the sperm
      chromatin was dispersed and contained protamines but was devoid of core histones
      H2B and H3. At 4 hr postinsemination, both protamine and core histones were
      detectable on the sperm chromatin. By 8 hr postinsemination protamines were
      absent, and histones stained maximally. The appearance of immunoreactive histones
      was correlated with a morphological transition of the sperm chromatin from the
      dispersed to a condensed state, which suggests that the assembly of the histones
      reflected modification of the chromatin to a somatic-like state in which it was
      competent to respond to the metaphase-promoting factor activity of the oocyte.
      Both the assembly of histones and chromatin condensation were reversibly blocked
      when protein synthesis was inhibited, indicating that the remodeling process
      required proteins synthesized during maturation. Injection of core histones into
      protein synthesis-inhibited oocytes failed to induce condensation of the sperm
      chromatin, which implies that correct remodeling requires synthesis during
      maturation of nonhistone proteins. To test the functional capacity of remodeled
      sperm chromatin, maturing oocytes were inseminated, allowed to continue
      maturation for 17 hr and then parthenogenetically activated. Following
      activation, the sperm-derived chromatin as well as that of the oocyte became
      decondensed within pronuclei and underwent DNA replication, indicating that sperm
      chromatin remodeled in maturing oocyte cytoplasm was functionally normal. When
      the postinsemination incubation time was reduced to 11 hr; however, neither the
      female nor the male pronuclei underwent DNA replication, implying that factors
      synthesized late during maturation are required for DNA replication after
      activation. Taken together, these results indicate that the ability to organize
      sperm DNA into functional somatic-like chromatin develops in oocytes during
      meiotic maturation, requires proteins synthesized during maturation, and can be
      expressed independently of activation.

PMID- 9188755
TI  - Identification of a male meiosis-specific gene, Tcte2, which is differentially
      spliced in species that form sterile hybrids with laboratory mice and deleted in
      t chromosomes showing meiotic drive.
AB  - Tcte2 (t complex testes expressed 2) is a male meiosis-specific gene that maps to
      band 3.3 of mouse chromosome 17. Two distinct male fertility defects, hybrid
      sterility and transmission ratio distortion, have previously been mapped to this
      region. Hybrid sterility arises in crosses between different mouse species and
      the F1 generation males have defects in the first meiotic division and are
      sterile. Transmission ratio distortion is shown by males heterozygous for the t
      haplotype form of chromosome 17 and is a type of meiotic drive in which male
      gametes function unequally at fertilization. The Tcte2 gene expresses a coding
      mRNA and a number of putative non-ORF transcripts in meiosis I. A deletion of the
      5' part of the locus abolishes Tcte2 expression on the t haplotype form of
      chromosome 17. Additionally, the series of putative non-ORF RNAs at the Tcte2
      locus are differentially spliced in species that show hybrid sterility when
      crossed to laboratory mice. The identification of polymorphisms in t haplotypes
      and in different mouse species allows alleles of Tcte2 to be proposed as
      candidates for loci which contribute to both meiotic drive and hybrid sterility
      phenotypes. While theoretical considerations have previously been used to propose
      that speciation and meiotic drive involve alleles of the same genes, Tcte2 is the
      first cloned candidate gene to support this link at a molecular level.

PMID- 9188756
TI  - Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells
      to cause a loss of forebrain in Xenopus embryos.
AB  - When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium
      ions, they develop with a loss of anterior structures. In the current study, we
      have characterized the neural defects produced by either Xwnt-8 or lithium and
      have examined potential cellular mechanisms underlying this anterior truncation.
      We find that the primary defect in embryos exposed to lithium at successively
      earlier stages during gastrulation is a progressive rostral to caudal deletion of
      the forebrain, while hindbrain and spinal regions of the CNS remain intact.
      Misexpression of Xwnt-8 during gastrulation produces an identical loss of
      forebrain. Our results demonstrate that lithium and Wnts can act upon either
      prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a
      loss of anterior pattern. Specifically, ectodermal cells isolated from lithium-
      or Wnt-exposed embryos are unable to form anterior neural tissue in response to
      inductive signals from normal dorsal mesoderm. In addition, although dorsal
      mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and
      produce normal levels of the anterior neural inducing molecules noggin and
      chordin, they show a greatly reduced capacity to induce anterior neural tissue in
      conjugated ectoderm. Taken together, our results are consistent with a model in
      which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal
      cells to produce a dominant posteriorizing morphogen which respecifies anterior
      neural tissue as posterior.

PMID- 9188758
TI  - Molecular mechanisms in the antiproliferative action of quercetin.
AB  - A single treatment with quercetin (5.5 microM), a plant flavonoid, activated both
      apoptosis and differentiation programs in K562 human leukemia cells. K562 cells
      expressed commitment to apoptosis after 1 h exposure, however, at least 12 h of
      drug exposure was needed to induce differentiation. Early (1 h) down-regulation
      of the c-myc and Ki-ras oncogenes and rapid reduction of inositol-1,4,5
      trisphosphate (IP3) concentration (IC50 = 9 microM, 1 h incubation) are part of
      the antiproliferative action of quercetin and appear to relate to induction of
      differentiation and/or apoptotic program of K562 leukemia cells treated with
      quercetin.

PMID- 9188757
TI  - Transdifferentiation of muscle to electric organ: regulation of muscle-specific
      proteins is independent of patterned nerve activity.
AB  - Transdifferentiation is the conversion of one differentiated cell type into
      another. The electric organ of fishes transdifferentiates from muscle but little
      is known about how this occurs. To begin to address this question, we studied the
      expression of muscle- and electrocyte-specific proteins with immunohistochemistry
      during regeneration of the electric organ. In the early stages of regeneration, a
      blastema forms. Blastemal cells cluster, express desmin, fuse into myotubes, and
      then express alpha-actinin, tropomyosin, and myosin. Myotubes in the periphery of
      the blastema continue to differentiate as muscle; those in the center grow in
      size, probably by fusing with each other, and lose their sarcomeres as they
      become electrocytes. Tropomyosin is rapidly down-regulated while desmin, alpha
      actinin, and myosin continue to be diffusely expressed in newly formed
      electrocytes despite the absence of organized sarcomeres. During this time an
      isoform of keratin that is a marker for mature electrocytes is expressed. One
      week later, the immunoreactivities of myosin disappears and alpha-actinin
      weakens, while that of desmin and keratin remain strong. Since nerve fibers grow
      into the blastema preceding the appearance of any differentiated cells, we tested
      whether the highly rhythmic nerve activity associated with electromotor input
      plays a role in transdifferentiation and found that electrocytes develop normally
      in the absence of electromotor neuron activity.

PMID- 9188759
TI  - Cold stress related alteration of RNA biosynthesis in brain cortex of mother
      deprived newborn rats.
AB  - We studied the influence of maternal deprivation on the RNA biosynthesis in the
      brain cortex of 10 day-old rats. Mother-deprived pups, placed at 25 degrees C
      showed a reduction in body temperature of 6 +/- 1 degree C. After mother
      retrieval, RNA biosynthesis decreased 27% and 34% in total brain cortex and in
      isolated neurons, respectively. This fall is proportional to the body temperature
      reduction and can be avoided placing the pups at 37 degrees C immediately after
      the separation. Rethermostatization of offsprings, after one hour at 25 degrees
      C, showed an overshoot of RNA biosynthesis (145%) with further stabilization of
      synthesis rates to normal levels after 100 min. This classical physiological
      mechanism was further studied in vitro. Comparing in vivo and in vitro
      experiments, it is concluded that overshooting can not be observed in vitro if
      temperature reduction was not previously performed in vivo. Thus, this phenomenon
      seems to respond to humoral factors in order to be triggered. Afterwards, in
      vitro overshooting following cold stress in vivo, demonstrates that the depressed
      tissue by itself has the capability to turn back to normal RNA levels in the same
      way as observed in vivo.

PMID- 9188760
TI  - Evidence that a mitogen-inducible prolactin-immunoreactive protein in rat spleen
      lymphocytes is aldolase A.
AB  - This study characterizes several proteins in rat spleen lymphocyte lysates and
      conditioned medium that are recognized by antiserum to purified rat pituitary
      prolactin (PRL). One of these proteins, rat prolactin-immunoreactive protein
      (rPIP-43), has a relative molecular mass (Mr) of 43,000 and is strongly induced
      by mitogenic stimulation in spleen lymphocytes. A constitutively expressed
      protein of this size also was detected in the IM-9 human B lymphoblastoid cell
      line and the Nb2 rat T lymphoma cell line. The N-terminal amino acid sequence of
      rPIP-43 in spleen lymphocyte lysate was analysed and found to be identical with
      25 residues at the N-terminus of the glycolytic enzyme aldolase A. In further
      experiments, the rPRL antiserum was evaluated for cross-reactivity with an
      aldolase A preparation and recognized a Mr 43,000 protein in rabbit muscle.
      Preabsorption of rPRL antiserum with rPRL was found to greatly decrease the
      intensity of staining of rPRL, aldolase A and rPIP-43. Preabsorption of antiserum
      with aldolase A had a similar, but less pronounced effect, with the aldolase A
      band and rPIP-43 being stained less intensely, while there was no effect on the
      intensity of staining of purified rPRL. Thus, data indicate that rPIP-43 is not a
      structural variant of PRL, but appears to be a different protein. These results
      have implications for the use of PRL antiserum to detect PRL in biological
      samples insofar as aldolase A is a ubiquitously expressed protein.

PMID- 9188761
TI  - Effect of acute hyperglycemia on basal and cholecystokinin stimulated exocrine
      pancreatic secretion in humans.
AB  - This study was undertaken to investigate the effect of acute hyperglycemia on
      pancreatico-biliary secretion in healthy subjects. Duodenal outputs of bilirubin,
      amylase, trypsin and bicarbonate were measured by aspiration using a recovery
      marker under basal condition for 75 min and during continuous infusion of CCK
      (0.5 IDU/kg.h for 60 min). Seven healthy subjects participated in two experiments
      performed in random order during normoglycemia and during acute hyperglycemic
      clamping at 15 mmol/l. At regular intervals plasma PP levels were determined as
      an indirect measure of vagal-cholinergic tone. Basal pancreatico-biliary
      secretion was significantly (p<0.05) reduced during acute hyperglycemia. CCK
      significantly (p<0.05) increased bilirubin, amylase and trypsin output both
      during normo- and hyperglycemia. During the initial 30 min of CCK infusion the
      bilirubin, amylase and trypsin outputs were significantly (p<0.05) inhibited in
      the hyperglycemic experiment compared to normoglycemia. In the following 30 min
      of CCK infusion the bilirubin, amylase and trypsin output were not different
      between hyper- and normoglycemia. Basal and CCK-stimulated plasma PP
      concentrations were significantly (p<0.05) reduced during hyperglycemia. In
      summary: 1) basal pancreatico-biliary secretion is significantly reduced during
      acute hyperglycemia 2) during hyperglycemia CCK-stimulated pancreatico-biliary
      secretion is also significantly reduced with the pattern of a delayed response 3)
      hyperglycemia inhibits basal and CCK-stimulated PP secretion suggesting impaired
      vagal-cholinergic activity during hyperglycemia.

PMID- 9188762
TI  - Evidence for tryptophan hydroxylase and hydroxy-indol-O-methyl-transferase mRNAs
      in human blood platelets.
AB  - Human blood platelets were tested for the presence of mRNAs coding for tryptophan
      hydroxylase (TPOH) and hydroxy-indol-o-methyl-transferase (HIOMT). Total RNA was
      extracted from platelets (12.9 +/- 3.3 mg RNA/100 ml blood, mean +/- SEM of 6
      preparations) and cDNA synthesized by reverse transcription using random
      hexamers, oligo-dT or TPOH- or HIOMT-specific primers, designed to amplify a 254
      bp fragment for TPOH and a 301 bp fragment for HIOMT. Positive controls were
      performed using RNA extracted from human normal or tumoral pineal glands. The PCR
      products were analyzed by gel electrophoresis, transferred to a nylon membrane
      and hybridized with a 32P-labeled internal probe. When random hexamers, oligo-dT
      or specific primers were used for reverse transcription, amplification products
      of the predicted sizes were detectable following electrophoresis in the case of
      pineal glands and following transfer and hybridization in the case of platelets.
      These results show TPOH and HIOMT mRNAs to be present in human blood and support
      the hypothesis that serotonin and melatonin may be synthesized in blood and, more
      particularly, in platelets.

PMID- 9188763
TI  - Nucleolar coefficient and cytochemistry of human blood monocytes.
AB  - Nucleoli in peripheral blood monocytes represented mostly by micronucleoli were
      investigated by means of cytochemical procedures for the demonstration of RNA,
      proteins of silver stained nucleolus organizer region, nucleophosmin, nucleolin
      and fibrillarin. The values of the nucleolar coefficient (mean number of nucleoli
      per cell) were influenced by the procedure used for the visualization of
      nucleoli. The differences in the values of the nucleolar coefficient of monocytes
      in one and the same person using above mentioned procedures suggested that
      micronucleoli in blood monocytes represent heterogeneous nuclear structures and
      only some of them possess both RNA and characteristic nucleolar proteins.
      Therefore, the procedures used for the visualization of nucleoli must be always
      taken into consideration when the values of the nucleolar coefficient are
      evaluated.

PMID- 9188764
TI  - Ischemic preconditioning reduces Op6 generation and prevents respiratory
      impairment in the mitochondria of post-ischemic reperfused heart of rat.
AB  - The present study was performed to test whether the ischemic preconditioning
      could reduce mitochondrial O2.- production and prevent mitochondrial respiratory
      impairment upon reperfusion of ischemic hearts. The isolated perfused rat hearts
      were subjected to 30 min of global ischemia and 20 min of reperfusion. Ischemic
      preconditioning was performed, involving three 5-min periods of ischemia, each
      followed by a 5-min reperfusion just before a sustained ischemia. Ischemic
      preconditioning improved the post-ischemic cardiac function and reduced LDH
      release and malondialdehyde production upon reperfusion. 02.- generation of
      mitochondria isolated from the preconditioned hearts was significantly lower than
      that of mitochondria from the non-preconditioned hearts, and none of the
      activities of mitochondrial antioxidant enzymes (SOD, catalase, glutathione
      peroxidase) was altered as a consequence of the ischemic preconditioning alone.
      The impairment of mitochondrial state 3 respiration induced by ischemia and
      reperfusion was prevented by ischemic preconditioning. Amytal, a reversible
      respiratory chain blocker suppressing 02.- production in mitochondria, prevented
      the ischemia/reperfusion injury. The cardioprotective effect of Amytal could not
      be distinguished from that of ischemic preconditioning. These results suggest
      that the cardioprotective effect of ischemic preconditioning against the
      ischemia/reperfusion injury is attributed partly to the reduction of
      mitochondrial oxygen radical generation and prevention of the respiratory
      impairment during ischemia and reperfusion.

PMID- 9188765
TI  - Hydrogen peroxide-mediated cytotoxicity to cultured colonic epithelial cells.
AB  - Reactive oxygen metabolites (ROM) contribute to colonic cellular injury, in
      certain pathophysiological conditions. We investigated the role of iron and
      individual metabolites in their cytotoxicity to cultured colonic epithelial cells
      from adult white rabbits. Reactive oxygen metabolites, enzymatically generated by
      hypoxanthine/xanthine oxidase, have a direct cytotoxic effect on cultured colonic
      epithelial cells. This cellular injury was inhibited by catalase but not SOD.
      Damage was not aggravated by ferrous iron or EDTA-chelated iron. Such damage was
      prevented by chelating intracellular iron, but not extracellular iron. These
      results suggest that H2O2 is more toxic to colonic epithelial cells than 02.- and
      OH. in the extracellular space. H2O2 enter the intracellular space and is
      converted to the more reactive and harmful OH. leading to cellular injury in the
      presence of intracellular iron.

PMID- 9188766
TI  - Electrophysiological properties of different cell types in the shark rectal
      gland.
AB  - Electrophysiological properties of different cell types were studied in single
      rectal gland cells of Squalus acanthias by the whole-cell voltage clamp
      technique. Based on electrophysiological characteristics and primary
      morphological observations (light microscope, X400), three cell types (named as
      I, II, and III) were found in isolated fresh cells and two cell types (I and II)
      in primary cultured cells of the shark rectal gland (SRG). Type I cells had both
      Cl- (I(Cl)) and the inwardly rectifying K+ channel (I(K1)). Type II and III cells
      only had I(Cl) Under X400 light microscope granular materials in the cytoplasm
      were found in Type I and II cells, but not in Type III cells. The data from this
      study show that 65 % of isolated fresh SRG cells strongly expressed the K+
      channel with much less amount of the Cl- channel and 35% had only I(Cl). In sharp
      contrast, 11% had I(K1) and I(Cl), and 89% had only I(Cl) in cultured SRG cells.
      Extracellular application of 10 microM forskolin significantly enhanced I(Cl) in
      primary cultured SRG cells. This enhancement was influenced by intracellular Ca2+
      and blocked by 50 microM Ni2+. Other compounds, such as vasoactive intestinal
      peptide (VIP) and 8-(4-chlorophenylthio)-adenosine3':5'-cyclic monophosphate (cpt
      cAMP) also enhanced I(Cl). Interestingly, cAMP and forskolin significantly
      inhibited I(K1) in cultured and fresh SRG cells. I(K1) was blocked by micromolar
      concentrations of Ba2+ and significantly altered by extracellular K+
      concentrations. The present data suggest that 1) the shark rectal gland contains
      different cell types which may play various roles in the process of salt
      secretion; 2) I(Cl) and I(K1) in SRG cells are strongly modulated by cAMP,
      forskolin, and VIP, as well as Ca2+, K+, and Na+ ions.

PMID- 9188767
TI  - In vivo regulation of serotonin 5-HT2A receptors in rat brain by subchronic
      administration of sigma receptor ligand NE-100.
AB  - In the present study, we examined the effect of the novel sigma receptor ligand
      NE-100 on 5-hydroxytryptamine-2A (5-HT2A) receptor binding in rat brain using an
      in vivo approach. Rats received intraperitoneal injections of either vehicle (1
      ml/kg) or NE-100 (3 mg/kg) twice daily for 14 days. The in vivo binding of [3H]RP
      62203, a selective 5-HT2A receptor radioligand, to 5-HT2A receptors in the rat
      brain was examined at 1, 3 or 7 days after final treatment. The specific binding
      of [3H]RP 62203 in the frontal cortex, parietal cortex and occipital cortex 1 day
      after subchronic administration of NE-100 was significantly increased as compared
      to animals treated with vehicle. In contrast, specific binding in the frontal
      cortex and parietal cortex 3 days after subchronic administration of NE-100 was
      significantly decreased as compared with the vehicle treated group. Seven days
      after the last injection of NE-100 or vehicle, there were no significant
      differences between the NE-100 and vehicle treated groups in [3H]RP 62203 binding
      in all the regions examined except for the hippocampus. These findings indicate
      that subchronic treatment with NE-100 may regulate the in vivo binding
      characteristics of 5-HT2A receptors in the cerebral cortex of rat brain.

PMID- 9188768
TI  - Nitric oxide regulatory role in sensitized guinea pig trachea.
AB  - Nitric oxide (NO) has been cited to play an important regulatory role in airway
      function. Moreover, the NO synthase expression in models of inflammation is
      documented. The aim of this study was to investigate, in vitro, the NO modulation
      of cholinergic responses in sham-sensitized and ovalbumin-sensitized guinea pig
      trachea by using L-arginine (L-ARG), a precursor of NO synthesis, and L-Ng-nitro
      arginine-methyl-ester (L-NAME), an inhibitor of NO synthase. Our results showed
      that NO's ability to modulate cholinergic responses in ovalbumin-sensitized
      guinea pig trachea is lost. Indeed L-ARG and L-NAME modify acetylcholine
      sensitivity in sham-sensitized guinea pig but not in ovalbumin-sensitized guinea
      pig.

PMID- 9188769
TI  - Alterations in methotrexate pharmacokinetics by naproxen in the rat as measured
      by microdialysis.
AB  - Reports of a potentially life-threatening interaction between the antifolate
      methotrexate (MTX) and drugs belonging to the NSAID class instigated a study of
      MTX pharmacokinetics by a microdialysis technique in the presence and absence of
      the NSAID naproxen in anesthetized rats. After pretreatment with naproxen, the
      animals received either 750 or 1,000 mg/kg MTX as a 6 h continuous intravenous
      infusion. During infusions, microdialysis effluents were obtained from probes
      situated intravenously, intrahepatically and intrarenally. In all three
      compartments, time-concentration AUCs for both MTX and its major extracellular
      metabolite, 7-hydroxymethotrexate (7-OH-MTX), increased about two-fold in the
      presence of naproxen. The mechanisms responsible for the MTX-NSAID interaction
      are briefly discussed. The study demonstrate that the microdialysis technique
      offers a means to investigate pharmacokinetic drug-drug interactions.

PMID- 9188770
TI  - S-8921, an ileal Na+/bile acid cotransporter inhibitor decreases serum
      cholesterol in hamsters.
AB  - The ileal Na+/bile acid cotransporter (IBAT) maintains the reabsorption of bile
      acids from the intestine in the enterohepatic circulation of bile acids. In the
      present study, we showed that S-8921 could dose-dependently inhibit the uptake of
      [3H] taurocholate in the COS7 cell line which constitutively expresses hamster
      IBAT. The IC50 value of S-8921 against 60 microM of [3H] taurocholate uptake was
      66 +/- 8 microM and kinetic analysis revealed that the inhibition by 100 microM
      of S-8921 was a mixture of competitive and non-competitive types. In vivo
      administration of S-8921 by its incorporation into diet (0.001-0.1%) caused dose
      dependent decrease of serum cholesterol concentrations accompanied by increased
      fecal excretion of bile acids in hamsters which were not loaded with cholesterol
      and bile acid. These data suggest that the inhibition of IBAT could decrease
      serum cholesterol in the non-cholesterol and -bile acid loaded normal condition.

PMID- 9188771
TI  - Rhodopsin phosphorylation in bovine rod outer segments is more sensitive to the
      inhibitory action of recoverin at the low rhodopsin bleaching than it is at the
      high bleaching.
AB  - Recoverin, a calcium-binding protein, is supposed to have rhodopsin kinase as a
      target in the retinal rod cell. In the present work, we show that efficiency of
      recoverin as an inhibitor of rhodopsin phosphorylation in bovine rod outer
      segments is inversely proportional to the level of rhodopsin bleaching. These
      results, together with the data obtained previously in a reconstituted system
      (Senin et al. (1997) Biochem. J. 321, 551-555), allow us to hypothesize that
      recoverin might be responsible for a Ca2(+)-dependent regulation of the kinase in
      vivo, preventing it from participating in the phosphorylation of unbleached
      rhodopsin.

PMID- 9188772
TI  - Transcriptional regulation of the human replacement histone gene H3.3B.
AB  - In contrast to the cell-cycle-dependent histone genes, replacement histone genes
      are transcribed independently of DNA replication and their expression is
      upregulated during differentiation. We have investigated the transcriptional
      regulation of the recently characterized human replacement histone gene H3.3B.
      Using reporter gene assays of promoter-luciferase gene-constructs, we show that
      promoter activity largely depends on an intact Oct and CRE/TRE element within the
      proximal 145 bp of the promoter. DNase I footprinting revealed binding of
      proteins to a 40-bp region covering these two elements. Band shift experiments
      identified binding proteins as Oct-1 and factors of the CREB/ATF and AP-1 family,
      respectively. The unexpected transcriptional regulation of this replacement
      histone gene is discussed.

PMID- 9188773
TI  - Receptor-mediated modulation of recombinant neuronal class E calcium channels.
AB  - The modulation of a cloned neuronal calcium channel was studied in a human
      embryonic kidney cell line (HEK293). The HEK293 cells were stably transfected
      with the alpha1Ed cDNA, containing the pore forming subunit of a neuronal class E
      calcium channel. Inward currents of 25 +/- 1.9 pA/pF (n = 79) were measured with
      the cloned alpha1Ed-subunit. The application of the peptide hormone somatostatin,
      carbachol, ATP or adenosine reduced the amplitude of Ca2+ and Ba2+ inward
      currents and exhibited a slowing of inactivation. This inhibitory effect by
      somatostatin was significantly impaired after pre-incubating the transfected cell
      line with pertussis toxin (PTX). Internal perfusion of the cells with the G
      protein-inactivating agent GDP-beta-S or with the permanently activating agent
      GTP-gamma-S also attenuated the somatostatin effect. The inhibition indicates
      that modulation of the alpha1Ed-mediated Ca2+ current involves pertussis toxin
      sensitive G-proteins. The block of Ca2+ and Ba2+ inward currents by somatostatin
      is also found in cells expressing a truncated alpha1Ed-subunit which lacks a 129
      bp fragment in the C-terminus. This fragment corresponds to the major structural
      difference between two native human alpha1E splice variants. As somatostatin
      inhibits inward currents through both, the cloned alpha1Ed- and the truncated
      alpha1Ed-DEL-subunit, the hormone-mediated modulation is independent from the
      presence of the 129-bp insertion in the C-terminus.

PMID- 9188774
TI  - The Ca2+/calmodulin binding domain of the Ca2+-ATPase linked to the Na+,K+-ATPase
      alters transport stoichiometry.
AB  - Using Xenopus oocytes as an expression system, we have investigated ion-transport
      and ouabain-binding properties of a chimeric ATPase (alpha1-CBD; Ishii and
      Takeyasu (1995) EMBO J. 14, 58-67) formed by the alpha1-subunit of chicken
      Na+,K(+)-ATPase (alpha1) and the calmodulin binding domain (CBD) of the rat
      plasma membrane Ca2(+)-ATPase. alpha1-CBD can be expressed and transported to the
      oocyte plasma membrane without the beta-subunit, and shows ouabain binding. In
      contrast to ouabain binding, this chimera requires the beta-subunit for its
      cation (Na+ and K+) transport activity. alpha1-CBD exhibits an altered
      stoichiometry of Na(+)-K+ exchange. A detailed analysis of 22Na+ efflux, 86Rb+
      uptake, pump current and ouabain binding suggests that the chimeric molecule can
      operate in an electrically silent 2Na(+)-2K+ exchange mode and, with much lower
      probability, in its normal 3Na(+)-2K+ exchange mode.

PMID- 9188775
TI  - Stabilization of photosystem two dimers by phosphorylation: implication for the
      regulation of the turnover of D1 protein.
AB  - A general feature of many membrane protein complexes is that they have oligomeric
      organisation in vivo. Photosystem II (PSII) is one such example and the possible
      functional significance of this is explored in this work. Monomeric and dimeric
      forms of the core complex of PSII have been isolated from non-phosphorylated and
      phosphorylated thylakoid membranes prepared from spinach. These complexes had the
      same complement of proteins including, D1 (PsbA), D2 (PsbD), alpha-(PsbE) and
      beta-(PsbF) subunits of cytochrome b559, CP47 (PsbB), CP43 (PsbC), 33 kDa (PsbO)
      extrinsic protein and some other smaller subunits, such as PsbH, but did not
      contain Cab proteins. D1, D2, CP43 and PsbH were the phosphorylated components.
      Whether phosphorylated or not, the dimeric form of the PSII complex was more
      stable than the monomeric form. However, when treated with photoinhibitory light
      the isolated dimers converted to monomers in their non-phosphorylated state but
      not when phosphorylated. Phosphorylation, however, did not prevent
      photoinhibition as judged by the loss of oxygen evolving activity. A model is
      suggested for the role of PSII phosphorylation in controlling the conversion of
      dimeric PSII to its monomeric form and in this way regulate the rate of
      degradation of D1 protein during the photoinhibitory repair cycle.

PMID- 9188777
TI  - A simple and rapid procedure for the purification of synthetic polypeptides by a
      combination of affinity chromatography and methionine chemistry.
AB  - Chemical synthesis of bioactive peptides has become a widespread and rapidly
      growing technique due to automated and efficient protocols for chain assembly.
      For most applications, the crude synthetic product must be purified to remove
      residual reactants, failure sequences and chemically modified peptide species. We
      propose here a method of universal applicability based on immobilized metal ion
      affinity chromatography, CNBr cleavage and use of reversible Met-sulfoxide
      protection. With this method we were able to purify to homogeneity in high yield
      the PbCS 242-310 polypeptide corresponding to the C-terminal region of Plasmodium
      berghei CS protein.

PMID- 9188776
TI  - Human L-3-phosphoserine phosphatase: sequence, expression and evidence for a
      phosphoenzyme intermediate.
AB  - We report the sequence of the cDNA encoding human L-3-phosphoserine phosphatase.
      The encoded polypeptide contains 225 residues and shows 30% sequence identity
      with the Escherichia coli enzyme. The human protein was expressed in a bacterial
      expression system and purified. Similar to known L-3-phosphoserine phosphatases,
      it catalyzed the Mg2(+)-dependent hydrolysis of L-phosphoserine and an exchange
      reaction between L-serine and L-phosphoserine. In addition we found that the
      enzyme was phosphorylated upon incubation with L-[32P]phosphoserine, which
      indicates that the reaction mechanism proceeds via the formation of a phosphoryl
      enzyme intermediate. The sensitivity of the phosphoryl-enzyme to alkali and to
      hydroxylamine suggests that an aspartyl- or a glutamyl-phosphate was formed. The
      nucleotide sequence of the cDNA described in this article has been deposited in
      the EMBL data base under accession number Y10275.

PMID- 9188778
TI  - Singlet oxygen mediates the activation of JNK by UVA radiation in human skin
      fibroblasts.
AB  - Ultraviolet A (UVA: 320-400 nm) radiation activates c-Jun-N-terminal kinase (JNK
      2) in human skin fibroblasts. Exposure of cells to UVA (300 kJ/m2) led to a 5
      fold induction of JNK-activity which was significantly increased in the presence
      of D2O, an enhancer of the lifetime of singlet oxygen. Sodium azide, a quencher
      of singlet oxygen, abolished the activation of JNK. A hydroxyl radical scavenger,
      mannitol, had no effect. Furthermore, photochemically produced singlet oxygen
      (Rose Bengal plus white light) was found to induce JNK activity. This was
      enhanced by D2O and inhibited by azide. Thus, singlet oxygen activates and
      mediates the UVA-induced activation of JNK.

PMID- 9188779
TI  - Detection of ERK activation by a novel monoclonal antibody.
AB  - The mitogen-activated protein kinase, ERK is activated by a dual phosphorylation
      on threonine and tyrosine residues. Using a synthetic diphospho peptide, we have
      generated a monoclonal antibody directed to the active ERK. The antibody
      specifically identified the active doubly phosphorylated, but not the inactive
      mono- or non- phosphorylated forms of ERKs. A direct correlation was observed
      between ERK activity and the intensity in Western blot of mitogen-activated
      protein kinases from several species. The antibody was proven suitable for
      immunofluorescence staining, revealing a transient reactivity with ERKs that were
      translocated to the nucleus upon stimulation. In conclusion, the antibody can
      serve as a useful tool in the study of ERK signaling in a wide variety of
      organisms.

PMID- 9188780
TI  - Melatonin prevents changes in microsomal membrane fluidity during induced lipid
      peroxidation.
AB  - We tested the effect of melatonin on membrane fluidity in microsomes of a rat
      liver model in which lipid peroxidation was induced by the addition of FeCl3, ADP
      and NADPH. Membrane fluidity was monitored using fluorescence spectroscopy and
      lipid peroxidation was estimated by quantifying malonaldehyde (MDA)+4
      hydroxyalkenals (4-HDA) concentrations following the induction of lipid
      peroxidation with and without pre-incubation with melatonin (1 microM-3 mM).
      Membrane rigidity increased during induced lipid peroxidation while melatonin
      reduced in a concentration-dependent manner both membrane rigidity and MDA+4-HDA
      generation. Melatonin's protective effect may relate to its known ability to
      scavenge free radicals and function as an antioxidant.

PMID- 9188782
TI  - Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in
      receptor-binding and in biological activities of Gas6.
AB  - Gas6 is a ligand for an Axl/Sky receptor tyrosine kinase subfamily and has a
      structure composed of a Gla domain, four EGF-like domains and a C-terminal sex
      hormone-binding globulin (SHBG)-like domain. When examining the role of each
      domain in receptor-binding and biological activities of Gas6, we found that
      receptor-binding and mitogenic activities were markedly reduced by inhibiting
      gamma-carboxylation of the Gla domain, while a Gas6 mutant composed of only an
      SHBG-like domain retained both of these activities. Thus, the SHBG-like domain is
      apparently an entity indispensable for Gas6 activities, and gamma-carboxylation
      of the Gla domain has a regulatory role in retaining the activity of native Gas6.

PMID- 9188781
TI  - Gastric GATA-6 DNA-binding protein: proteolysis induced by cAMP.
AB  - The rat gastric GATA DNA-binding protein, GATA-6 (GATA-GT1), was stably expressed
      in CHO-K1 cells. The GATA-6 protein was localized in the nucleus but not in the
      cytoplasm. Interestingly, when cells were treated with dibutyryl cAMP, the GATA-6
      protein was specifically degraded. Such a phenomenon was not observed in the
      presence of 5'-AMP or dibutyryl cGMP. The cellular level of the GATA-6 protein
      was restored upon removal of dibutyryl cAMP. Degradation was also induced by
      cholera toxin, which increased the cellular cAMP concentration, and was inhibited
      by a protein kinase A inhibitor. However, activators of protein kinase C did not
      have any effect. The degradation was inhibited by proteasome inhibitors (PSI
      (benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal) and MG115 (benzyloxycarbonyl-Leu
      Leu-norvalinal)) but not by those of lysosomes and serine proteases. These
      results suggest that a kinase-mediated protein phosphorylation is the cellular
      signal for degradation of the GATA-6 protein. This finding constitutes a novel
      aspect of regulation by GATA DNA-binding proteins, which are essential for
      developmental processes and tissue-specific transcription.

PMID- 9188783
TI  - Identification and characterization of a cyanobacterial DnaX intein.
AB  - A new intein is identified and characterized in the DnaX protein of Synechocystis
      sp. PCC6803. This cyanobacterial DnaX protein is a homologue of the intein-less
      71-kDa tau-subunit of Escherichia coli DNA polymerase III and is related to
      eukaryotic DNA replication factor C (RFC). The 430-residue DnaX intein contains
      several putative intein sequence motifs and undergoes protein splicing when
      produced in E. coli cells. Its position in the DnaX protein is close to, but
      different from, positions of three inteins present in a DnaX-related RFC protein
      of Methanococcus jannaschii.

PMID- 9188784
TI  - Aluminum fluoride associates with the small guanine nucleotide binding proteins.
AB  - AlF4- has long been known to associate with and activate the GDP-bound alpha
      subunits of heterotrimeric G-proteins. Recently the small guanine nucleotide
      binding protein Ras has also been shown to associate with AlF4- in the presence
      of stoichiometric amounts of its GTPase activating protein (GAP). Here we present
      the isolation of a stable Ras x GDP- x AlF4- x GAP ternary complex by gel
      filtration. In addition, we generalise the association of AlF4- with the small
      GTP-binding proteins by demonstrating ternary complex formation for the Cdc42,
      Rap and Ran proteins in the presence of their respective GAP proteins.

PMID- 9188785
TI  - Intensity-independent fluorometric detection of cellular nitric oxide release.
AB  - A new fluorescence method is introduced in which nitric oxide (NO)-derived higher
      order oxygen complexes (NO(x)) are quantified at physiological pH. Detecting the
      fluorescence lifetime shift between 2,3-diaminonaphthalene and the NO(x)-derived
      protonated 2,3-naphthotriazole allows an intensity independent determination of
      the NO(x) concentration. The NO release from LPS and IFNgamma-stimulated murine
      macrophages and iNOS transfected hamster cells was quantified. The lower
      detection limit for NO2- was found to be 800 pmol/ml. Since the influence of
      static fluorescence quenching due to cellular components can be neglected, the
      method is applicable for clear cellular supernatants as well as turbid cellular
      suspensions.

PMID- 9188786
TI  - Excess substrate inhibition of soybean lipoxygenase-1 is mainly oxygen-dependent.
AB  - Soybean lipoxygenase-1 kinetics are known to show product and substrate
      inhibition. With linoleic acid as the substrate and using a simple Michaelis
      Menten formulation, we have shown that K(ss), the substrate inhibition constant
      was increased by more than five-fold when initial oxygen concentration was
      increased from 228 to 1140 microM. Excess substrate inhibition is in fact almost
      avoided at high initial oxygen concentration. This modification seems correlated
      with enzyme saturation with oxygen relative to linoleic acid, as reflected by
      alterations of the substrate conversion rate. Possible implications for the
      enzyme kinetics are discussed.

PMID- 9188787
TI  - Microinjected cDNA encoding JAK2 protein-tyrosine kinase induces DNA synthesis in
      NIH 3T3 cells.
AB  - Microinjection of expression plasmids encoding either JAK2 or hyperactive
      (Ndelta661)rJAK2 into serum-starved NIH 3T3 cells resulted in 20-30-fold
      induction of DNA synthesis. Control microinjections of buffer or parental pcDNA3
      vector resulted in only 3-5-fold induction of DNA synthesis. Induction of DNA
      synthesis was blocked when plasmid encoding JAK2 was microinjected in the
      presence of the JAK2-selective inhibitor AG-490, whereas AG-490 did not block DNA
      synthesis induced by microinjected plasmid encoding (Ndelta661)rJAK2. The ability
      of JAK2 to initiate the G(o)/S cell cycle transition is comparable to that of
      other proto-oncogenes, and supports a mechanistic role for overexpressed Janus
      kinases in carcinogenesis.

PMID- 9188788
TI  - Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein
      in vascular endothelial cells.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is rapidly tyrosine
      phosphorylated in mechanically stimulated vascular endothelial cells (ECs). A 65
      kDa protein from ECs specifically bound to the c-Src phosphorylated PECAM-1
      cytoplasmic domain and was identified as a protein tyrosine phosphatase SH-PTP2
      (SHP2, Syp). PECAM-1 was coimmunoprecipitated by anti-SH-PTP2 from EC extracts as
      a major binding protein, and the level of association increased when PECAM-1 was
      tyrosine phosphorylated. This association was mediated by SH2 domains of SH-PTP2.
      A rapid translocation of SH-PTP2 into cell-cell adhesion sites, where PECAM-1 was
      localized, occurred in mechanically stimulated cells. Our results suggest that
      PECAM-1 is a component of a mechanosensing machinery acting upstream of SH-PTP2.

PMID- 9188789
TI  - Interaction between the CheY response regulator and the histidine-containing
      phosphotransfer (HPt) domain of the ArcB sensory kinase in Escherichia coli.
AB  - Bacteria have devised sophisticated His-Asp phosphorelay signaling systems for
      eliciting a variety of adaptive responses to their environment. The histidine
      containing phosphotransfer (HPt) domain, found in many signal transduction
      protein, functions as a mediator of the His-Asp phosphorelay. The ArcB anaerobic
      sensor of E. coli contains such a HPt domain, although its function is not fully
      understood. In this study, we provide in vivo and in vitro evidence that the HPt
      domain is capable of interacting with the CheY receiver, which contains a phospho
      accepting aspartate residue.

PMID- 9188790
TI  - Laminin-alpha2 but not -alpha1-mediated adhesion of human (Duchenne) and murine
      (mdx) dystrophic myotubes is seriously defective.
AB  - It has been suggested that alpha-dystroglycan links the dystrophin-associated
      protein complex and extracellular matrix and that the absence of dystrophin and
      alpha-dystroglycan in Duchenne muscular dystrophy (DMD) may lead to the breakdown
      of this linkage. In the present study, myotubes from DMD patients and murine X
      linked muscular dystrophic mice (mdx) were used to measure their adhesive force
      to the physiological laminin-alpha2 substrate, and it was found that the
      dystrophic myotubes were selectively unable to sustain adhesion. However, normal
      and dystrophic myotubes attached equally well to the laminin-alpha1 substrate. As
      far as we know, this is the first experimental evidence that the absence of
      dystrophin causes the complete loss of a still unknown laminin-alpha2-dependent
      adhesion force, therefore suggesting that the primary consequence of Duchenne
      dystrophy consists of the loss of an authentic mechanical linkage at the level of
      the alpha-dystroglycan/basal lamina interface.

PMID- 9188791
TI  - Dual regulation of heat-stable enterotoxin-mediated cGMP accumulation in T84
      cells by receptor desensitization and increased phosphodiesterase activity.
AB  - We report the regulation of cGMP accumulation induced by the heat-stable
      enterotoxin, STh, in the T84 human colonic cell line. STh binding to its
      receptor, guanylyl cyclase C (GCC), leads to elevated intracellular levels of
      cGMP. Prolonged exposure of T84 cells to STh induced refractoriness to further
      cGMP accumulation, without significant receptor internalization, but with reduced
      STh-induced cGMP synthesis by the receptor. Significantly, increased degradation
      of cGMP by a cGMP-specific phosphodiesterase was observed in desensitized cells.
      This is the first report on the desensitization of GCC, as well as the role of
      the Type V phosphodiesterase in inducing cellular refractoriness.

PMID- 9188792
TI  - Postimport methylation of the small subunit of ribulose-1,5-bisphosphate
      carboxylase in chloroplasts.
AB  - Electron impact mass spectronomy analysis of the amino-terminal amino acid of the
      small subunit (SSU) of ribulose-1,5-bisphosphate carboxylase (Rubisco) showed
      that the amino-terminal methionine residue is post-translationally modified to N
      methyl-methionine. Modification of the amino-terminal methionine residue was
      found in mature SSU proteins from the dicotyledonous plants pea and spinach as
      well as the monocotyledonous plants barley and corn. SSU methyltransferase is a
      soluble protein in the chloroplast stroma and accepts heterologously expressed
      non-methylated SSU as a substrate using S-adenosylmethionine as methyl-group
      donor. We show that this modification occurs after post-translational uptake of
      the precursor form of SSU into chloroplasts and processing to its mature size.
      This reaction represents a new step in the import and assembly pathway of Rubisco
      holoenzyme.

PMID- 9188793
TI  - Ribosome-inactivating lectins with polynucleotide:adenosine glycosidase activity.
AB  - Lectins from Aegopodium podagraria (APA), Bryonia dioica (BDA), Galanthus nivalis
      (GNA), Iris hybrid (IRA) and Sambucus nigra (SNAI), and a new lectin-related
      protein from Sambucus nigra (SNLRP) were studied to ascertain whether they had
      the properties of ribosome-inactivating proteins (RIP). IRA and SNLRP inhibited
      protein synthesis by a cell-free system and, at much higher concentrations, by
      cells and had polynucleotide:adenosine glycosidase activity, thus behaving like
      non-toxic type 2 (two chain) RIP. APA and SNAI had much less activity, and BDA
      and GNA did not inhibit protein synthesis.

PMID- 9188794
TI  - Cloning of a cDNA encoding a putative metal-transporting P-type ATPase from
      Arabidopsis thaliana.
AB  - Metal-transporting P-type ATPases were recently proposed to constitute a newly
      emerged sub-family of cation-transporting P-type ATPases, and are known to occur
      widely in prokaryotes and eukaryotes. However, no instance has been reported for
      higher plants. A cDNA clone encoding a metal-transporting P-type ATPase was thus
      searched for, if present, and was identified in Arabidopsis thaliana. The amino
      acid sequence, predicted from the determined nucleotide sequence for the cloned
      cDNA, shows all the critical features common to known metal-transporting P-type
      ATPases. This plant P-type ATPase has a typical metal-binding motif at its N
      terminal portion. The newly isolated Arabidopsis gene, named PAA1, provides us
      with the first instance of putative metal-transporting P-type ATPases in higher
      plants. Some results of genomic analyses for this gene are also presented.

PMID- 9188795
TI  - The carboxyl-terminal sequence of rat intestinal mucin RMuc3 contains a putative
      transmembrane region and two EGF-like motifs.
AB  - A 3' RACE technique was used to establish the nucleotide sequence encoding the C
      terminal 379 amino acids of rat intestinal Muc3. Unlike the C-terminus of Muc2
      and many secretory mucins, Muc3 contains two EGF motifs and a putative
      transmembrane domain. The mRNA for rat Muc3 is 7.5-8.0 kb.

PMID- 9188796
TI  - Anthracyclines modulate multidrug resistance protein (MRP) mediated organic anion
      transport.
AB  - We studied the ATP-dependent uptake of dinitrophenyl-glutathione (GS-DNP) into
      plasma membrane vesicles derived from parental GLC4 cells and from multidrug
      resistant GLC4/ADR cells. The latter have a high expression of the multidrug
      resistance protein (MRP). Uptake of GS-DNP into membrane vesicles from GLC4/ADR
      cells was highly stimulated by the addition of ATP, compared to the uptake into
      membrane vesicles from GLC4 cells. This ATP-dependent uptake into membrane
      vesicles from GLC4/ADR cells was saturable with a Km of 1.2 +/- 0.2 microM and a
      Vmax of 560 +/- 80 pmol/mg prot./min. ATP stimulated GS-DNP uptake with a Km of
      187 +/- 4 microM. This uptake was specifically inhibited by a polyclonal serum
      raised against a fusion protein containing a segment of MRP. The ATP-dependent
      uptake of GS-DNP was not only inhibited by organic anions, such as oxidized
      glutathione (GSSG), methotrexate (MTX) and some bile acids, but also by non
      anionic natural product drugs, such as anthracyclines, vinca alkaloids and
      etoposide (VP-16). Uptake of GSSG and MTX into membrane vesicles from GLC4/ADR
      cells could be stimulated by ATP. The ATP-dependent uptake of GSSG had a Km of 43
      +/- 3 microM and a Vmax of 900 +/- 200 nmol/mg protein/min. The ATP-dependent
      uptake of GS-DNP seemed to be non-competitively inhibited by the anthracycline
      daunorubicin (DNR), whereas the ATP-dependent GSSG uptake seemed to be
      competitively inhibited by DNR. A substrate binding site on MRP is proposed that
      comprises a pocket in which both DNR and GS-DNP or GSSG bind in random order to
      different, only partly overlapping sites. In this pocket binding of a second
      compound is influenced by the compound which was bound first.

PMID- 9188797
TI  - The hydrophobic region of signal peptides is involved in the interaction with
      membrane-bound SecA.
AB  - The positive charges of signal peptides are important for the interaction with
      SecA, a translocation ATPase. To examine whether or not the hydrophobic region of
      signal peptides also interacts with SecA, we constructed model preproteins,
      proOmpF-Lpps, possessing no positively charged amino acid residues at the amino
      terminus and different numbers of alanine/leucine residues in the hydrophobic
      region of signal peptides. When the hydrophobic stretch was sufficiently long,
      amino-terminal positively charged residues were not required for the
      translocation of preproteins across the cytoplasmic membrane of Escherichia coli
      both in vitro and in vivo. Chemical cross-linking between SecA and preproteins
      possessing no positively charged residues at the amino-terminus was observed only
      in the presence of liposomes containing acidic phospholipids. The degree of cross
      linking increased as the length of the hydrophobic stretch increased irrespective
      of whether positively charged residues were present or not. A preprotein
      possessing no positively charged residues at the amino-terminus, which is
      competent in the presence of liposomes, competitively inhibited the cross-linking
      of wild-type proOmpF-Lpp with SecA under the same conditions. It is concluded
      that both the amino-terminal positive charges and central hydrophobic domains are
      involved in the interaction with SecA in the initial stage of translocation in
      addition to their possible roles in transmembrane movement of preproteins.

PMID- 9188799
TI  - Ion-channels formed by hypelcins, antibiotic peptides, in planar bilayer lipid
      membranes.
AB  - Ion-channel properties of native hypelcins (HP) A-I, A-V and B-V isolated from
      Hypocrea peltata and a synthetic analog, HP-A-Pheol, were studied in planar
      bilayer lipid membranes by a single-channel recording technique. The native and
      synthetic hypelcins formed ion-channels with three conductance levels for 3 mole
      dm(-3) KCl: < or = 0.09 nS at 225 mV (level 0, only detectable at voltages above
      200 mV), approximately 0.6 nS at 150 mV (level 1, most common level) and
      approximately 3 nS at 150 mV (level 2). The effects of the C-terminal
      aminoalcohol on the channel properties were examined with HP-A-I, HP-A-V and HP-A
      Pheol, whose C-termini are leucinol (Leuol), isoleucinol (Ileol) and
      phenylalaninol (Pheol), respectively. The substitution of Pheol for Leuol and
      Ileol prolonged the open channel lifetime. A comparison of HP-A-V (Gln18) and HP
      B-V (Glu18) indicated that the carboxyl group at position 18 increased both the
      open channel lifetime and the magnitude of unitary channel conductance at each
      conductance level. The pores of level 1 showed poor ion-selectivity for K+ over
      Cl-. The selectivity order of alkali metal cations was Rb > or = Cs > or = K > Na
      > Li for level 1 and Cs > Rb > K > Na > Li for level 0. The unitary current
      voltage characteristics showed non-linear relationships, which were simulated by
      a Nernst-Planck approach with a simple barrier model.

PMID- 9188798
TI  - Reactive liposomes encapsulating a glucose oxidase-peroxidase system with
      antibacterial activity.
AB  - Liposomes were prepared from phospholipid mixtures of
      dipalmitoylphosphatidylcholine (DPPC) and phosphatidylinositol (PI),
      encapsulating the enzymes glucose oxidase (GO) and GO in combination with horse
      radish peroxidase (HRP) by both extrusion (VET) and reverse-phase evaporation
      (REV). The optimum level of PI in DPPC/PI liposomes for targeting to biofilms of
      the oral bacterium Streptococcus gordonii has been established. The liposomes
      were characterised in terms of the content and activity of the encapsulated
      enzymes. The antibacterial activity of these 'reactive' liposomes arising from
      hydrogen peroxide and oxyacids in the presence of the substrates glucose and
      iodide ions, after targeting to the biofilms, were measured both as a function of
      liposome-biofilm incubation time and incubation time with the substrates.
      Bacterial inhibition increases with both liposome-biofilm and substrate-biofilm
      incubation time and with the extent of enzyme encapsulation. The reactive
      liposomes also display antibacterial activity in the presence of saliva. The
      reactive liposomes have potential value in the context of oral hygiene.

PMID- 9188800
TI  - Association of polyene antibiotics with sterol-free lipid membranes. II.
      Hydrophobic binding of nystatin to dilauroylphosphatidylcholine bilayers.
AB  - Interaction of nystatin A1 with multilamellar vesicles (MLV) of
      dilauroylphosphatidylcholine (DLPC), observed either by adding nystatin to
      preformed MLV (mixtures I) or by incorporating it during the formation of
      vesicles (mixtures II, inner lamellas of MLV in contact with nystatin) was
      investigated for 0.002 < or = nystatin/DLPC = R(A) < or = 0.20, by four
      complementary methods. The main results were: (i) Ultraviolet absorption and
      circular dichroism (CD) spectra of mixtures I revealed the occurrence of a
      saturable association with a stoichiometry (R(A) = 0.007 +/- 0.002) constant
      between 3 and 33 degrees C. (ii) By differential scanning calorimetry,
      thermograms of the two types of mixtures were similar only when water was in
      great excess. In the opposite (e.g., (H2O)/(DLPC) = R(W) < or = 300), mixture II
      thermograms displayed two features, upshifted by about 6.5 degrees C with respect
      to the sharp peak observed with mixture I, resembling those obtained for pure
      DLPC when the low-temperature phase was the subgel phase. For this R(W), the
      nystatin absolute concentrations were those for which nystatin form
      superaggregates as revealed by the nystatin CD spectra. It is proposed that these
      superaggregates are excluded from the interlamellar spacings of MLV and exert a
      pumping action on the interlamellar water. The subsequent dehydration of the
      inner lamellas is thought to convert them into the subgel state. (iii) 2H-NMR
      spectra of sn-2-perdeuterated DLPC MLV + nystatin mixtures II, confirmed such a
      temperature shift of the main transition. They showed, in addition, an ordering
      of the aliphatic chains immediately above the transition temperature, equivalent
      to a bilayer thickening of 2 A.

PMID- 9188801
TI  - Chemical modifications of striatal A2A adenosine receptors: a possible role for
      tyrosine at the ligand binding sites.
AB  - A2A adenosine receptors were examined in bovine striatal membranes following
      exposure to tetranitromethane (TNM) which modifies tyrosine and cysteine
      residues. TNM (0.05-0.5 mM) treatment caused an irreversible, concentration
      dependent decrease in the binding activity of the selective A2A agonist [3H]CGS
      21680. Protection studies showed that TNM inactivation could be prevented by the
      adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) and by the
      antagonist xanthine amine congener (XAC), suggesting that TNM modified residues
      at the ligand-binding sites. Scatchard analysis of the binding data showed that
      0.15 mM TNM decreased the [3H]CGS 21680 Bmax value from 447 +/- 39 to 273 +/- 21
      fmol/mg of proteins without any significant change in the Kd values (13.5 +/- 1.4
      and 14.7 +/- 1.5 for control and treated membranes, respectively). We carried out
      a series of successive chemical modifications with the reducing agent
      dithiothreitol (DTT), which indicated that the residues modified by TNM, under
      our experimental conditions, are tyrosine residues and not cysteine residues.

PMID- 9188802
TI  - The direct cause of photodamage-induced lysosomal destabilization.
AB  - Whether membrane lipid photoperoxidation is the immediate cause for lysosomal
      lysis is still unclear. In this study, we investigated the direct causal factor
      of photoinduced lysosomal destabilization in a K+-containing solution. Methylene
      blue (MB)-mediated photodamage caused lysosomal membrane lipid peroxidation and
      loss of membrane fluidity. Compared with unirradiated lysosomes, the photodamaged
      lysosomes significantly lost enzyme latency in an isotonic K+-containing solution
      during a 20-min period of incubation. It indicates an increase in lysosomal K+
      permeability. The inward K+ permeation of photodamaged lysosomes was further
      proved by a K+-induced elevation of internal membrane potential. In addition, the
      photodamaged lysosomes displayed an increased osmotic sensitivity, showing that
      MB-mediated photodamage promotes lysosomal osmotic fragility. Although these
      photoinduced alterations occurred, the lysosomes were relatively stable in an
      isotonic sucrose medium. In contrast, the organelle destabilized in a photodamage
      dependent fashion in an isotonic K+-containing solution. The results indicate
      that membrane lipid peroxidation does not definitely destabilize lysosomes. The
      direct cause for the lysosomal destabilization is photoinduced osmotic imbalance
      across its membrane via an increased K+ uptake, while the increase in osmotic
      sensitivity favors the destabilization of photodamaged lysosomes.

PMID- 9188803
TI  - Characteristics of the melibiose transporter and its primary structure in
      Enterobacter aerogenes.
AB  - Cells of Enterobacter aerogenes can grow on melibiose as a sole source of carbon.
      This suggests the presence of melibiose operon in this organism. We found that E.
      aerogenes cells possess both alpha-galactosidase activity and melibiose transport
      activity, which were induced by melibiose. Neither Na+ nor Li+ stimulated the
      melibiose transport. However, transport of methyl-beta-thiogalactoside (TMG) was
      stimulated by Li+ but not by Na+. These findings suggest that the major coupling
      cation for the melibiose transporter in E. aerogenes is H+. In fact, we observed
      H+ entry into cells caused by an influx of melibiose and some of its analogs. We
      cloned the melB gene which encodes the melibiose transporter, and sequenced it.
      Deduced amino acid sequence of the transporter revealed that the melibiose
      transporter consists of 471 amino acid residues and the molecular weight was
      calculated to be 52214 Da. The sequence showed high homology with the sequences
      of the melibiose transporters of Escherichia coli, Salmonella typhimurium and
      Klebsiella pneumoniae. Higher homology was found with the melibiose transporter
      of K. pneumoniae than with that of E. coli and S. typhimurium.

PMID- 9188805
TI  - X-ray diffraction study of bilayer to non-bilayer phase transitions in aqueous
      dispersions of di-polyenoic phosphatidylethanolamines.
AB  - The low temperature phase properties of aqueous dispersions of di-18:2 and di
      18:3 phosphatidylethanolamine are strongly influenced by the presence of ice. In
      the presence of cryoprotectants to inhibit ice formation, these lipids persist in
      the H(II) phase down to at least -50 degrees C. Ice formation, however, leads to
      a drastic reduction in the amount of available free water and a rapid reduction
      in the diameter of the inverted cylindrical micelles of the H(II) phase. The
      resulting increase in surface curvature of the micelles induces an imbalance in
      the forces acting in the lipid surface and the hydrophobic core which is relieved
      by formation of the L(alpha) phase. On reheating the lipid samples undergo an
      abrupt L(alpha) --> H(II) phase transition at about -20 degrees C. The radius of
      the water core of the inverted micelles at their point of formation is estimated
      to be 0.9 nm. This increases with temperature as more unfrozen water becomes
      available until the normal equilibrium radius of about 2.3 nm is reached at 0
      degrees C when the bulk water in the sample finally melts. A small proportion of
      the H(II) phase lipid enters an as yet unidentified cubic phase on freezing. The
      spacings of the (10) planes of the H(II) phase, the (111) planes of the cubic
      phase and the d-spacing of the L(alpha) phase were found to be almost identical
      at the phase transition temperature. The cubic phase appears to disappear at low
      temperature but to reform on heating. Freeze-fracture studies revealed no
      unequivocal evidence for cubic phase lipid but the presence of residual non
      bilayer lipid structures was observed even at temperatures as low as -80 degrees
      C. The presence of intersecting stacks of lamellar sheets in the replicas
      strongly suggest the existence of an epitaxial relationship between the L(alpha)
      and H(II) phases in these systems.

PMID- 9188804
TI  - Substrate specificity of the mammary tissue anionic amino acid carrier operating
      in the cotransport and exchange modes.
AB  - The substrate specificity of the rat mammary tissue high affinity, Na+-dependent
      anionic amino acid transport system has been investigated using explants and the
      perfused mammary gland. D-Aspartate appears to be transported via the high
      affinity, Na+-dependent L-glutamate carrier. Thus, D-aspartate transport by rat
      mammary tissue was Na+-dependent and saturable with respect to extracellular D
      aspartate with a Km and Vmax of 32.4 microM and 49.0 nmol/2 min per g of cells
      respectively. The uptake of D-aspartate by mammary explants was cis-inhibited by
      L-glutamate and L-aspartate, but not by D-glutamate. L-glutamate uptake by
      mammary tissue explants was cis-inhibited by beta-glutamate, L-cysteate, L
      cysteine sulfinate and dihydrokainate but not by DL-alpha-aminoadipate. In
      addition, dihydrokainate, but not DL-alpha-aminoadipate inhibited D-aspartate and
      L-glutamate uptake by the perfused gland. D-Aspartate efflux from mammary tissue
      explants was trans-accelerated by external L-glutamate in a dose-dependent
      fashion (50-500 microM). The effect of L-glutamate on D-aspartate efflux was
      dependent on the presence of extracellular Na+. D-Aspartate, L-aspartate and L
      cysteine sulfinate (at 500 microM) also markedly trans-stimulated D-aspartate
      efflux from mammary tissue explants. In contrast, L-cysteine. D-glutamate, L
      leucine, dihydrokainate and DL-alpha-aminoadipate were either weak stimulators of
      D-aspartate efflux or were without effect. D-Aspartate efflux from the perfused
      mammary gland was trans-stimulated by L-glutamate but not by D-glutamate and only
      weakly by L-cysteine (all at 500 microM). It appears that the mammary tissue high
      affinity anionic amino acid carrier can operate in the exchange mode with a
      similar substrate specificity to that of the co-transport mode.

PMID- 9188806
TI  - The organochlorine pesticide heptachlor disrupts the structure of model and cell
      membranes.
AB  - Heptachlor is an organochlorine pesticide which is particularly toxic for aquatic
      life. A significant source of this pesticide for infants is breast milk, where
      its concentration is considerably higher than in dairy milk. Given the lipophilic
      character of heptachlor, lipid-rich cell membranes are a very plausible target
      for its interaction with living organisms. In order to evaluate its toxicity
      towards cell membranes, heptachlor was made to interact with human erythrocytes
      and molecular models of the red cell membrane. These consisted of multilayers of
      dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine
      (DMPE), which are types of phospholipids that are respectively located in the
      outer and inner monolayers of the erythrocyte membrane, and large unilamellar
      vesicles (LUV) of DMPC. Observations by scanning electron microscopy showed that
      10 mM heptachlor produced various degrees of shape alterations to erythrocytes,
      which ranged from a few blebs in some cells to a great number of protuberances in
      others. On the other hand, experiments performed by X-ray diffraction on DMPC and
      DMPE indicated that the bilayer structure of DMPC was much more affected by
      heptachlor than that of DMPE. Measurements by fluorescence spectroscopy on DMPC
      LUV confirmed the X-ray diffraction results in that both the hydrocarbon chain
      and polar head regions of DMPC were structurally perturbed by heptachlor. The
      results obtained from the model studies could explain the shape changes induced
      to red cells by heptachlor. According to the bilayer hypothesis, they were due to
      the preferential interaction of heptachlor with the phosphatidylcholine-rich
      external moiety of the erythrocyte membrane. It is therefore concluded that toxic
      effects of this pesticide can be related to its capacity to perturb the
      phospholipid bilayer structure, whose integrity is essential for cell membrane
      functions.

PMID- 9188807
TI  - Calcium-induced bilirubin-dependent hemolysis of human erythrocytes.
AB  - Human erythrocytes, preincubated with different concentrations of calcium
      chloride (0.17-1.67 mM) showed hemolysis after addition of bilirubin (72 microM).
      Hemolysis was observed only when cells were incubated first with calcium followed
      by bilirubin and not vice versa. This hemolysis was found to be dependent upon
      several factors such as concentration of bilirubin, time of incubation of
      erythrocytes with calcium and time of incubation of bilirubin with the calcium
      loaded erythrocytes. Inclusion of EDTA in the incubation medium reduced the
      percentage hemolysis to a significant extent. Involvement of activated oxygen
      species in hemolytic process seems to be unlikely as inclusion of sodium azide
      and catalase did not prevent hemolysis. A comparison of other bivalent cations
      such as Ba2+, Mg2+, Mn2+ and Cu2+ with Ca2+ for their ability to hemolyse cells
      in presence of bilirubin shows that Ba2+ and Mg2+ are ineffective, whereas both
      Mn2+ and Cu2+ induce hemolysis both in the absence as well as in the presence of
      bilirubin. However, their mechanism of hemolysis is different from that of
      calcium-induced hemolysis. Formation of calcium-induced hydrophobic aggregates of
      phospholipid molecules in erythrocyte membrane may open the new binding sites for
      bilirubin on these membranes which may perturb the membrane conformation.

PMID- 9188808
TI  - Cholecystokinin regulates glycoprotein membrane composition of rat pancreatic
      zymogen granules.
AB  - Lectin-binding studies were performed on rat pancreatic zymogen granules to
      investigate the alterations in the carbohydrate membrane composition under both
      chronic CCK stimulation and long-term CCK blockade for 3, 7 and 15 days. By flow
      cytometry using FITC-WGA--which specifically binds to N-acetylglucosamine and
      sialic acid--we measured the amount of WGA molecules bound to each individual
      granule. Parallel studies on pancreatic secretion were also carried out. CCK
      treatment displayed a differential effect on two zymogen granule subpopulations
      (Z1 and Z2) identified by flow cytometry on the basis of their light scatter
      properties: no effects on Z2 zymogen granules were observed in CCK-treated rats,
      while Z1 granules showed a significant increase in WGA binding at day + 7 which
      coincides with an increase in protein secretion in response to the hormone. On
      the contrary, a significant decrease in the amount of WGA receptors was observed
      in zymogen granule membrane of both the Z1 and Z2 subsets of rats subjected to a
      long-term CCK blockade. Again, these changes parallel to the reduction observed
      in protein secretion. Our results suggest that glycoconjugates of zymogen granule
      membrane involved in CCK-regulated exocytosis contain N-acetylglucosamine and
      sialic acid residues whose quantities are regulated by CCK.

PMID- 9188809
TI  - Determination of the amount of native structural bacteriorhodopsin in purple
      membrane Langmuir-Blodgett films by a spectroscopic surface denaturation
      quantifying technique.
AB  - Purple membrane (PM) shows denaturation when spread over an air/water interface.
      We established a technique, which we call the spectroscopic surface denaturation
      quantifying (SSDQ) technique, that uses infrared linear dichroism to determine
      the amount of native structural bacteriorhodopsin (BR) in PM Langmuir-Blodgett
      (LB) films. Using the SSDQ technique we found that the conformational change
      after surface denaturation of BR was the same as that caused by ethanol
      treatment. By extrapolating the data of the amount of non-denatured BR molecules
      in PM LB films vs. the area of a single BR molecule on an air/water interface, we
      also found that the surface area of a single non-denatured BR molecule was 11.5
      nm2, which is consistent with that determined by high-resolution electron cryo
      microscopy and electron diffraction (EMD). These results demonstrate that the
      SSDQ technique is effective in quantifying the amount of native structural BR in
      PM LB films. The SSDQ technique is also applicable to other types of protein
      consisting of alpha-helical conformation.

PMID- 9188810
TI  - Translocation of annexin XI to neutrophil subcellular organelles.
AB  - In an earlier study, annexin XI was found to be present in the cytosol of
      neutrophil granulocytes (Blood (1996) 87, 4817). The protein was isolated by
      calcium-dependent translocation to specific granules and was found to be a 42-kDa
      truncated form of annexin XI. Using human autoantibodies directed against annexin
      XI we have now reinvestigated the ability of full size annexin XI to translocate
      to different neutrophil organelles isolated by subcellular fractionation. The
      autoantisera used recognised a protein of 55-kDa in neutrophil cytosol and
      comparison with a whole cell lysate indicated that the larger portion of the
      cellular content of this protein is localised to the cytosol. Azurophil granules,
      specific granules and secretory vesicles/plasma membrane were isolated by
      subcellular fractionation on Percoll gradients, mixed respectively with
      neutrophil cytosol and the calcium concentration was raised. Immunoblotting
      showed that annexin XI translocated to specific granules and secretory
      vesicles/plasma membrane at 100 micromol/l calcium. When raising the
      concentration of calcium to 1 mmol/l, annexin XI translocated to the azurophil
      granules as well. Periphagosomal translocation of annexin XI occurred during
      phagocytosis of yeast particles, implying that this protein plays a role in the
      events associated with the phagocytic process.

PMID- 9188811
TI  - Site-directed mutagenesis of hepatitis A virus protein 3A: effects on membrane
      interaction.
AB  - Due to a stretch of hydrophobic amino acids, protein 3A of hepatitis A virus
      (HAV) has been suggested to act as a membrane anchor or a carrier of the genome
      linked protein 3B (VPg) during viral RNA synthesis. Mutagenesis analysis was
      performed in order to elucidate the role of the N- and C-terminal tracts of
      protein 3A in cell membrane interaction. Expression of the mutated proteins in E.
      coli cells demonstrated that the presence of positively charged residues at the C
      terminus is not required for membrane anchoring. Changes in the primary sequence
      involving charged amino acids at the N- and C-termini critically influenced the
      ability of the protein 3A of a cytopathic strain of HAV to change bacterial
      membrane permeability. This result demonstrates the strict correlation between
      the structure and pore-forming potential of HAV protein 3A.

PMID- 9188812
TI  - Molecular species analysis of phospholipids.
AB  - The elucidation of phospholipid molecular species composition provides detailed
      structural information concerning various lipids and thus offers descriptions of
      crucial determinants of membrane physical and biological properties. Various
      methods differing in labor intensity, mode of separation and detection, type of
      calibration, as well as other factors, have been published. Thus precision and
      accuracy are expected to vary considerably between methods. Qualitative and
      quantitative aspects of different procedures for molecular species analysis of
      individual phospholipid classes are discussed in this review. Special emphasis
      has been given to the characterization of biological tissue samples.

PMID- 9188813
TI  - Determination of dimethylated arginines in human plasma by high-performance
      liquid chromatography.
AB  - Using high-performance liquid chromatography (HPLC) with multigradient elution,
      N(G),N(G)-dimethyl-L-arginine (asymmetric-DMA, ADMA) and N(G),N'(G)-dimethyl-L
      arginine (symmetric-DMA, SDMA) can be separated from human plasma samples. The
      dimethylarginine compounds in plasma, after extraction with a cation-exchange
      column, are converted to fluorescent derivatives with o-phthaldialdehyde (OPA) in
      an alkaline medium and the derivatives are separated simultaneously within 50 min
      on a reversed-phase column (Ultracarb 3 ODS(20)). The recoveries of ADMA and SDMA
      are over 80% and the method permits quantitative determination of dimethylated
      arginines at concentrations as low as 0.1 micromol/l in human plasma.

PMID- 9188815
TI  - Development of a purification procedure for the placental protein 14 involving
      metal-chelate affinity chromatography and hydrophobic interaction chromatography.
AB  - Placental protein 14 was isolated from the biological material of patients
      undergoing legal abortions. The major part of ballast protein was removed by ion
      exchange chromatography on DEAE-Sepharose and CM-Sepharose. Albumin was separated
      by chromatography on Blue-Sepharose. Complete purification was obtained by metal
      chelate affinity chromatography on Nickel-Chelate Sepharose and hydrophobic
      interaction chromatography on Phenyl-Sepharose and Octyl-Sepharose. The protein
      was not exposed to denaturing agents or extreme pH.

PMID- 9188814
TI  - Analytical partitioning of poly(ethylene glycol)-modified proteins.
AB  - Covalently grafting proteins with varying numbers (n) of poly(ethylene glycol)
      molecules (PEGs) often enhances their biomedical and industrial usefulness.
      Partition between the phases in aqueous polymer two-phase systems can be used to
      rapidly characterize polymer-protein conjugates in a manner related to various
      enhancements. The logarithm of the partition coefficient (K) approximates
      linearity over the range O<n<x. However, x varies with the nature of the
      conjugate (e.g., protein molecular mass) and such data analysis does not
      facilitate the comparison of varied conjugates. The known behavior of surface
      localized PEGs suggests a better correlation should exist between log K and the
      weight fraction of polymer in PEG-protein conjugates. Data from four independent
      studies involving three proteins (granulocyte-macrophage colony stimulation
      factor, bovine serum albumin and immunoglobulin G) has been found to support this
      hypothesis. Although somewhat simplistic, 'weight fraction' based analysis of
      partition data appears robust enough to accommodate laboratory to laboratory
      variation in protein, polymer and phase system type. It also facilitates
      comparisons between partition data involving disparate polymer-protein
      conjugates.

PMID- 9188816
TI  - Human pre-alpha-inhibitor: isolation from a by-product of industrial scale plasma
      fractionation and structural analysis of its H3 heavy chain.
AB  - Pre-alpha-inhibitor (P alpha I) is a serine proteinase inhibitor from human
      plasma. It comprises bikunin (BK) responsible for antiprotease activity,
      covalently linked to a heavy chain H3. Here we describe its isolation from a side
      fraction of an industrial preparation of plasma clotting factors. By using a
      highly specific polyclonal antiserum prepared from rabbit immunized with a H3P
      polypeptide obtained in a bacterial expression system, we were able to identify
      the fractions containing P alpha I. Then, taking advantage of the differential
      affinity of the members of the inter-alpha-inhibitor family (I alpha I) for
      heparin-Sepharose and blue-Sepharose, we isolated P alpha I. Its specific
      antitryptic activity was 580 IU/g, higher than that of I alpha I: 420 IU/g. Its
      M(r), determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis,
      with or without prior reduction, was 130,000. Its peptide chains were identified
      by N-terminal sequencing. The H3 heavy chain was isolated from P alpha I by
      alkaline dissociation and anion-exchange chromatography. Its electrophoretic
      mobility was compared to that of the HI and H2 heavy chains of I alpha I. In
      reducing conditions, it was quite similar to that of H2 (M(r) 85,000) but clearly
      different from that of H1 (M[r] 78,000). Thus, the so-determined apparent M(r) of
      H3 was overestimated since its molecular mass determined by MALDI-TOF was 74,100.
      This result agrees with the proposed structure for H3. Indeed, by carbohydrate
      analysis and PNGase F digestion, we demonstrate that the two potential N
      glycosylation sites present in the core-protein (theoretical mass: 69,454) are
      really occupied by two N-glycans, probably of biantennary type.

PMID- 9188817
TI  - Quantitative separation of 4-hydroxyproline from skeletal muscle collagen by
      micellar electrokinetic capillary electrophoresis.
AB  - The phenylthiohydantoin (PTH) derivatives of 3- and 4-hydroxyproline (Hyp) were
      separated using micellar electrokinetic capillary electrophoresis (MEKC). The
      separation protocol was also used to determine Hyp content of bovine skeletal
      perimysial collagen preparations and whole muscle samples. Amino acids from
      hydrolyzed tissues were labeled using a two step procedure that involved initial
      reaction with o-phthalaldehyde (OPA) to modify primary amines followed by their
      precipitation under acidic conditions. In the second step, imino acids were
      reacted with phenyl isothiocyanate (PITC). This labeling method was rapid and the
      Hyp values determined in these biological samples were found to be in close
      agreement with conventional methods and other published reports.

PMID- 9188818
TI  - Two-dimensional high-resolution electrophoresis of elastin-derived peptides.
AB  - Degradation of human aortic elastin in vivo yields a restricted number of
      differentially sized and charged peptides. Elastin-derived peptides (EDP) can be
      analyzed by two-dimensional electrophoresis after their extraction from human
      abdominal aortic tissue by 0.2 M sodium chloride. The peptides were separated
      according to charge by acetic acid-urea-PAGE and then according to molecular mass
      by SDS-PAGE. The identity of these peptides as EDP was continued by
      immunoprecipitation and Western blots. The two-dimensional electrophoretic system
      can resolve desmosine-like cross-linked EDP of the similar molecular
      configuration but differing in the number of positively charged amino acid
      residues. The new separation technique of EDP has the capacity to identify
      defects in desmosine-like cross-links and may be useful in characterizing
      abberations in elastin structures.

PMID- 9188819
TI  - Application of a new high-performance liquid chromatographic method for measuring
      selected polyphenols in human plasma.
AB  - We developed a method to measure plasma levels of selected polyphenols before and
      after ingestion of green tea. Blood samples were obtained from four healthy women
      before and 30 and 50 min after the ingestion of 300 ml of green tea infusion. A 1
      ml volume of plasma was hydrolysed with 0.5 M HCl-methanol (1:1, v/v) for 30 min
      at room temperature, extracted with ethyl acetate and separated by reversed-phase
      chromatography. Polyphenols were identified on the basis of their retention times
      and by spectrum analysis. Green tea caffeine has the same retention times as
      caffeic acid. Consumption of green tea produces a notable increase in the plasma
      levels of caffeine plus caffeic acid and the appearance of measurable levels of
      epigallocatechingallate. In conclusion, the method was found to have the
      requisite features of specificity and sensitivity for monitoring plasma levels of
      selected tea polyphenols.

PMID- 9188820
TI  - Application of ion mobility spectrometry to the rapid screening of
      methamphetamine incorporated in hair.
AB  - Using ion mobility spectrometry (IMS), a simple, sensitive and rapid screening
      for methamphetamine (MA) incorporated in user's hair has been developed. To
      completely unbind MA from hair matrix and to achieve its effective vaporization
      for the IMS detection, the hair sample was digested in 5 M NaOH (methanol-water,
      4:1, v/v) solution prior to IMS measurement. MA in hair was semi-quantitatively
      detected by monitoring the digested hair sample employing dibenzylamine (DBA) as
      internal standard. The minimum amount of hair sample required was 2 mg and its
      digested sample was ample for four IMS measurements. The detection limit of MA in
      hair was 0.5 ng mg(-1). This proposed method was applicable to the semi
      quantitative detection of MA in users' hair samples, and to the sectional
      analysis for MA in a limited amount of user's hair. The IMS results obtained were
      in good agreement with their GC-MS determination.

PMID- 9188821
TI  - Determination of LSD and N-demethyl-LSD in urine by liquid chromatography coupled
      to electrospray ionization mass spectrometry.
AB  - A sensitive and highly specific method for the determination of LSD and N
      demethyl-LSD in urine, using combined liquid chromatography and mass spectrometry
      (LC-MS) with electrospray ionization, has been developed. Extrelut-3 extraction
      cartridges were used for a basic sample clean-up. Elution was obtained by toluene
      diethyl ether (60:40, v/v). A Nucleosil C18 (150 X 1 mm I.D.) reversed-phase
      column was used for the chromatographic separation, together with a mixture of 2
      mM ammonium formate buffer (pH 3) and acetonitrile (70:30, v/v) as mobile phase.
      Recoveries were 93 and 80%, detection limits 0.025 and 0.035 ng/ml for LSD and N
      demethyl-LSD, respectively. Intra-assay precision, studied at four
      concentrations, was better than 9% at the ng/ml range and better than 14% at 0.10
      ng/ml for both compounds. Limits of quantitation were 0.05 and 0.10 ng/ml for LSD
      and N-demethyl-LSD, respectively. Reproducibility was good and linearity
      excellent for LSD in the range from 0.05 to 20 ng/ml (r>0.9999, n=7).

PMID- 9188822
TI  - Direct analysis of fluoxetine and norfluoxetine in plasma by gas chromatography
      with nitrogen-phosphorus detection.
AB  - A quantitative method for the simultaneous GC resolution and detection of
      fluoxetine and his metabolite norfluoxetine in human plasma was developed. The
      procedure required 1.0 ml of plasma, extraction with a mixed organic solvent and
      injection into a capillary gas chromatograph with an OV-1 fused-silica column
      coupled to a nitrogen-phosphorus detector. The calibration curves were linear
      over the range 5-3000 ng/ml. The detection limits were 0.3 and 2 ng/ml for
      fluoxetine and norfluoxetine, respectively. The assay is suitable for routine
      analysis.

PMID- 9188823
TI  - Quantitative colorimetric and gas chromatographic determination of arecaidine
      propargyl ester.
AB  - Arecaidine propargyl ester (APE) is a potent muscarinic agonist often used in
      pharmacological studies. To date, no sensitive quantitative analytical method for
      APE has been published. In this study, two methods for the quantitative
      determination of APE are compared: a colorimetric assay, based on the formation
      of the corresponding ferric(III)-hydroxamic acid complex, and a direct gas
      chromatographic method, using arecoline as the internal standard. The latter
      method was found to be more precise. The utility of the gas chromatographic assay
      was further demonstrated in a stability study of the drug in the biological fluid
      aqueous humor of rabbits.

PMID- 9188824
TI  - Confirmatory assay for the determination of tetracycline, oxytetracycline,
      chlortetracycline and its isomers in muscle and kidney using liquid
      chromatography-mass spectrometry.
AB  - A confirmatory method is described for the determination of tetracycline,
      oxytetracycline and chlortetracycline in muscle and kidney using liquid
      chromatography-atmospheric pressure chemical ionisation mass spectrometry. The
      tetracyclines were extracted from tissue using glycine-HCl buffer and
      concentrated using solid-phase extraction. HPLC separation was carried out using
      a gradient and the tetracyclines were detected using a bench-top LC-MS system.
      Several ions could be monitored for each tetracycline, allowing ion ratio
      measurements to be made. The detection limits for the assay were in the region of
      10 ng/g in muscle and 20 ng/g in kidney. Validation was carried out at half the
      maximum residue limit, the maximum residue limit and two times the maximum
      residue limit. The formation of epimers and tautomers of the tetracyclines, their
      presence in incurred tissues and difficulties in their accurate quantitation is
      discussed.

PMID- 9188825
TI  - High-performance liquid chromatographic analysis of amoxicillin in human and
      chinchilla plasma, middle ear fluid and whole blood.
AB  - We extended the application of a sensitive high-performance liquid chromatography
      assay of amoxicillin developed in this laboratory for human plasma and middle ear
      fluid (MEF) to other sample matrices including chinchilla plasma or MEF and human
      and chinchilla whole blood with minor modification and validated the limit of
      quantitation at 0.25 microg/ml with a 50-microl sample size for human and
      chinchilla plasmas or MEFs. Amoxicillin and cefadroxil, the internal standard,
      were extracted from 50 microl of the samples with Bond Elut C18 cartridges. The
      extract was analyzed on a Keystone MOS Hypersil-1 (C8) column with UV detection
      at 210 nm. The mobile phase was 6% acetonitrile in 5 mM phosphate buffer, pH 6.5
      and 5 mM tetrabutylammonium. The within-day coefficients of variation were 2.7
      9.9 (n=4) and 1.7-7.2% (n=3) for chinchilla plasma and MEF samples, respectively;
      2.8-8.1% (n=3) and 2.9-4.7% (n=3) for human and chinchilla whole blood,
      respectively. An alternative mobile phase composition for chinchilla plasma and
      MEF samples reduced the analysis time significantly.

PMID- 9188826
TI  - Development of a chromatographic method for the isolation and detection of
      hygromycin B in biological fluids.
AB  - An affinity chromatography method was developed for the purification of
      hygromycin B from biological fluids. Lysozyme and alpha-lactalbumin were
      immobilized on an N-hydroxysuccinimide activated agarose support. Hygromycin B
      solubilized in water was bound by the proteins and subsequently eluted using 10
      mM sodium citrate buffer, pH 4.0. Hygromycin B was purified from swine plasma,
      bovine serum and bovine milk samples using a combination of ion-exchange
      chromatography for initial clean-up of spiked biological samples followed by
      affinity chromatography. Thin layer chromatographic analysis of the isolated
      hygromycin B revealed one band with the same R(F) value as the hygromycin B
      standard.

PMID- 9188827
TI  - Simultaneous analysis of several non-steroidal anti-inflammatory drugs in human
      urine by high-performance liquid chromatography with normal solid-phase
      extraction.
AB  - A practical and reproducible high-performance liquid chromatographic method using
      normal solid-phase extraction has been developed for the simultaneous analysis of
      twelve non-steroidal anti-inflammatory drugs (NSAIDs) in human urine. A urine
      specimen mixed with acetate buffer pH 5.0 was purified by solid-phase extraction
      on a Sep-Pak Silica cartridge. The analyte was chromatographed by a reversed
      phase Inertsil ODS-2 column using a phosphate buffer-acetonitrile at pH 5.0 as
      the mobile phase, and the effluent from the column was monitored at 230 or 320
      nm. Absolute recoveries were greater than 73% for all of the twelve NSAIDs. The
      present method enabled simple manipulation and isocratic HPLC with UV analysis as
      well as high sensitivity of 0.005 microg/ml for naproxen, and 0.05 microg/ml for
      sulindac, piroxicam, loxoprofen, ketoprofen, felbinac, fenbufen, flurbiprofen,
      diclofenac, ibuprofen and mefenamic acid as the quantitation limit in human urine
      using indomethacin as an internal standard.

PMID- 9188828
TI  - High-performance liquid chromatographic method for determination of DX-9065a, a
      novel anticoagulant, in human urine and feces using cation-exchange solid-phase
      extraction.
AB  - A simple HPLC method for determination of DX-9065a in human urine and feces was
      developed. The drug was extracted by Bond Elut CBA, a cation-exchange solid-phase
      extraction cartridge. The extracted drug was analyzed by HPLC with UV detection
      at 242 nm. With this extraction procedure, no interfering peaks were observed.
      The method developed was validated and showed adequate precision and accuracy.
      This method was applied to human clinical samples obtained from healthy Japanese
      volunteers who had orally received the drug. Using this method, the excretion
      profile of the drug in human after oral administration was revealed for the first
      time.

PMID- 9188829
TI  - Determination of N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine and its
      metabolites in human plasma and urine by column-switching high-performance liquid
      chromatography with ultraviolet detection.
AB  - A simple, rapid and sensitive two column-switching high-performance liquid
      chromatographic (HPLC) method with ultraviolet detection at 210 nm has been
      developed for the determination of N-(trans-4-isopropylcyclohexanecarbonyl)-D
      phenylalanine (AY4166, I) and its seven metabolites in human plasma and urine.
      Measurements of I and its metabolites were carried out by two column-switching
      HPLC, because metabolites were classified into two groups according to their
      retention times. After purification of plasma samples using solid-phase
      extraction and direct dilution of urinary samples, I and each metabolite were
      injected into HPLC. The calibration graphs for plasma and urinary samples were
      linear in the ranges 0.1 to 10 microg ml(-1) and 0.5 to 50 microg ml(-1),
      respectively. Recoveries of I and its seven metabolites were over 88% by the
      standard addition method and the relative standard deviations of I and its
      metabolites were 1-6%.

PMID- 9188830
TI  - Forensic analysis of eleven cyclic antidepressants in human biological samples
      using a new reversed-phase chromatographic column of 2 microm porous
      microspherical silica gel.
AB  - A high-performance liquid chromatographic method has been developed for the
      forensic analysis of eleven frequently used cyclic antidepressant drugs (ADSs)
      (amitriptyline, amoxapine, clomipramine, desipramine, dosulepine, doxepin,
      imipramine, maprotiline, melitracen, mianserine and nortriptyline) using a
      recently developed reversed-phase column with 2 microm particles for the analysis
      of biological samples. The separation was carried out using two different C8
      reversed-phase columns (column 1: 100 mm X 4.6 mm I.D., particle size 2 microm,
      TSK gel Super-Octyl; column 2: 100 mm X 4.6 mm I.D., particle size 5 microm,
      Hypersil MOS-C8) for comparison. The mobile phase was composed of methanol-20 mM
      KH2PO4 (pH 7) (60:40, v/v) and the flow-rate was 0.6 ml/min for both columns. The
      absorbance of the eluent was monitored at 254 nm. When the eleven drugs were
      determined, the sensitivity with the 2 microm particles was about five times
      greater than with the 5 microm particles. Retention times on column 1 were
      shorter than those on column 2. These results show that the new ODS column
      packing with a particle size of 2 microm gives higher sensitivity and a shorter
      analysis time than the conventional ODS column packing when applied to the
      analysis of biological samples.

PMID- 9188831
TI  - Determination of the halothane metabolites trifluoroacetic acid and bromide in
      plasma and urine by ion chromatography.
AB  - Halothane (CF3CHClBr), a widely used volatile anesthetic, undergoes extensive
      biotransformation in humans. Oxidative halothane metabolism yields the stable
      metabolites trifluoroacetic acid and bromide which can be detected in plasma and
      urine. To date, analytical methodologies have either required extensive sample
      preparation, or two separate analytical procedures to determine plasma and urine
      concentrations of these analytes. A rapid and sensitive method utilizing high
      performance liquid chromatography-ion chromatography (HPLC-IC) with suppressed
      conductivity detection was developed for the simultaneous detection of both
      trifluoroacetic acid and bromide in plasma and urine. Sample preparation required
      only ultrafiltration. Standard curves were linear (r2> or =0.99) from 10 to 250
      microM trifluoroacetic acid and 2 to 5000 microM bromide in plasma and 10 to 250
      microM trifluoroacetic acid and 2 to 50 microM bromide in urine. The assay was
      applied to quantification of trifluoroacetic acid and bromide in plasma and urine
      of a patient undergoing halothane anesthesia.

PMID- 9188833
TI  - Determination of 5-fluorouracil and its main metabolites in plasma by high
      performance liquid chromatography: application to a pharmacokinetic study.
AB  - This paper describes a relatively simple and sensitive high-performance liquid
      chromatographic assay (HPLC) with ultraviolet absorbance detection for 5
      fluorouracil (5-FUra) and its two main metabolites, 5-fluorouridine (5-FUrd) and
      5-fluoro-2'-deoxyuridine (5-FdUrd), in plasma. In this study, two plasma clean-up
      procedures involving addition of internal standard, solid-phase and liquid-liquid
      extractions have been developed. A reversed-phase Kromasil C18 column was used.
      The detection was performed at 268 nm for 5-FUra and at 275 nm for the two
      metabolites. Linear detection responses were obtained for concentrations ranging
      from 25 to 1000 ng/ml. The average recovery from plasma was 35, 42 and 48% for 5
      FUra, 5-FUrd and 5-FdUrd, respectively. Precision, expressed as C.V., ranged from
      2.7 to 13% and the mean recovery from 94 to 105%. The limits of quantitation and
      detection of the three analytes were 20 and 10 ng/ml, respectively. The method
      was used to monitor the pharmacokinetic profile of 5-FUra and its two metabolites
      in patients with metastatic colorectal cancer.

PMID- 9188832
TI  - Determination of D-fenfluramine, D-norfenfluramine and fluoxetine in plasma,
      brain tissue and brain microdialysate using high-performance liquid
      chromatography after precolumn derivatization with dansyl chloride.
AB  - A HPLC method is described for the simultaneous determination of D-fenfluramine
      (FEN), D-norfenfluramine (NF) and fluoxetine (FLX) using fluorometric detection
      after precolumn derivatization with dansyl-chloride. The method has limits of
      quantitation of 200 fmol for FEN and NF, 500 fmol for FLX in brain
      microdialysate, and 1 pmol for NF and FEN, and 2 pmol for FLX in plasma. Brain
      tissue standards were linear between 5 and 200 pmol/mg for all three compounds.
      The inter-assay variability (relative standard deviation) was 6.6%, 6.9% and 9.3%
      for FEN, 4.6%, 3.7% and 7.9% for NF and 10.4%, 4.9% and 12.2% for FLX, for brain
      microdialysate (2 pmol/microl), plasma (2 pmol/ microl) and brain tissue (50
      pmol/mg), respectively. Intra-assay variability was always lower, typically
      several times lower than inter-assay variability. Extraction recovery was 108%
      and 48% for FEN, 105% and 78% for NF and 94% and 45% for FLX, in plasma (2
      pmol/microl) and brain tissue (5 pmol/mg), respectively. Due to the stability of
      the dansyl-chloride derivatives this method is well suited for an autoinjector
      after manual derivatization with dansyl chloride at room temperature for 4 h.

PMID- 9188834
TI  - Validation of a high-performance liquid chromatographic assay method for
      pharmacokinetic evaluation of busulfan.
AB  - The development and validation of a high-performance liquid chromatographic
      (HPLC) assay for determination of busulfan concentrations in human plasma for
      pharmacokinetic studies is described. Plasma samples containing busulfan and 1,6
      bis(methanesulfonyloxy)hexane, and internal standard, were prepared by
      derivatization with sodium diethyldithiocarbamate (DDTC) followed by addition of
      methanol and extraction with ethyl acetate. The extract was dried under nitrogen
      and the samples reconstituted with 100 microl of methanol prior to HPLC
      determination. Chromatography was accomplished using a Waters NovaPak
      octadecylsilyl (ODS) (150 x 3.9 mm I.D.) analytical column, NovaPak ODS guard
      column, and mobile phase of methanol-water (80:20, v/v) at a flow-rate of 0.8
      ml/min with UV detection at 251 nm. The limit of detection was 0.0200 microg/ml
      (signal-to-noise ratio of 6) with a limit of quantitation (LOQ) of 0.0600
      microg/ml for busulfan in plasma. Calibration curves were linear from 0.0600 to
      3.00 microg/ml in plasma (500 microl) using a 1/y weighting scheme. Precision of
      the assay, as represented by C.V. of the observed peak area ratio values, ranged
      from 4.41 to 13.5% (13.5% at LOQ). No day-to-day variability was observed in
      predicted concentration values and the bias was low for all concentrations
      evaluated (bias: 0 to 4.76%; LOQ: 2.91%). The mean derivatization and extraction
      yield observed for busulfan in plasma at 0.200, 1.20 and 2.00 microg/ml was 98.5%
      (range 93.4 to 107%). Plasma samples containing potential busulfan metabolites
      and co-administered drugs, which may be present in clinical samples, provided no
      response indicating this assay procedure is selective for busulfan. This method
      was used to analyze plasma concentrations following administration of a 1 mg/kg
      oral busulfan dose.

PMID- 9188835
TI  - Determination of thiamphenicol in human plasma by micellar electrokinetic
      capillary chromatography.
AB  - A micellar electrokinetic chromatographic method is described for the
      determination of thiamphenicol in human plasma. The plasma sample was basified by
      adding K2HPO4 and was then extracted with ethyl acetate. After the solvent was
      evaporated, the residue was reconstituted in water. Approximately 40 nl of the
      solution were injected hydrodynamically. The running buffer was 20 mM borate (pH
      9.2) containing 40 mM sodium dodecyl sulfate and 10% acetonitrile. The applied
      voltage was 18 kV and the detector wavelength was set at 195 nm. On-column sample
      stacking was achieved during the analysis to enhance the sensitivity; the limit
      of quantitation was 0.1 microg/ml. Linearity was over the range of 0.2 to 10
      microg/ml. Recovery was 93.7+/-3.3%, the intra-day precision and accuracy was
      99.6+/-2.8%; the inter-day precision and accuracy was 98.4+/-3.4%. The
      concentration of thiamphenicol in human plasma from eight volunteers was measured
      after administering thiamphenicol capsules orally.

PMID- 9188836
TI  - Capillary electrophoresis with laser-induced fluorescence detection, an adequate
      alternative to high-performance liquid chromatography, for the determination of
      ciprofloxacin and its metabolite desethyleneciprofloxacin in human plasma.
AB  - A method to determine plasma concentrations of ciprofloxacin and its metabolite
      desethyleneciprofloxacin (M1) by CE with HeCd laser-induced fluorescence
      detection is described. Following precipitation of proteins and centrifugation
      supernatant is injected hydrodynamically (10 s, 0.5 p.s.i.) into the capillary.
      Overall analysis time for the quantification of both analytes was 7 min. The
      total amount of plasma needed for multiple injections (n>5) was 10-20 microl.
      Data on accuracy and precision are presented. The assay performance is compared
      to the specifications of a validated HPLC method, which is routinely used for the
      quantification of ciprofloxacin and M1 in body fluids. Both methods showed
      comparable accuracy and precision for both analytes throughout the whole working
      range (inter-day precision <9%; inter-day accuracy 96-110%). The limit of
      quantification (LOQ) of 20 microg/l (M1 10 microg/l) for the CE procedure was
      slightly higher than for the HPLC method, where 10 microg/l (M1 2.5 microg/l) was
      determined. However, application of the methods to human plasma samples derived
      from a clinical study proved that comparable results are obtained and that the
      sensitivity of the HPCE method was sufficient to fully describe typical plasma
      concentration time profiles of ciprofloxacin and its metabolite M1. Both the
      adequate sensitivity and the required smaller sample volume compared to HPLC
      indicate that the method is feasible for clinical studies where sample amounts
      are limited, e.g., studies to investigate pharmacokinetics in pediatric patients.
      Preclinical studies form another possible application of this technique.

PMID- 9188837
TI  - Efficient method for the quantitation of urinary leukotriene E4: extraction using
      an Empore C18 disk cartridge.
AB  - We describe here an efficient procedure for the precise quantitation of
      leukotriene E4 (LTE4) in a small volume of urine, which was achieved mainly by
      the use of an Empore extraction disk cartridge. After addition of [3H]LTE4 to 2
      ml of urine, an Empore C18 cartridge was used for initial extraction of the
      urine, which resulted in the extraction of LTE4 in a small volume of solvent. The
      eluate could then be injected onto a high-performance liquid chromatography
      column without further concentration. After separation by high-performance liquid
      chromatography, LTE4 was extracted from the effluent using an Empore C18
      cartridge. The concentration of LTE4 was subsequently quantified by enzyme
      immunoassay. LTE4 can be recovered from urine with sufficient efficiency (69.9+/
      4.7%, mean+/-S.D., n=101). The coefficient of variation of the assay procedure
      was less than 10%. When urine was spiked with different amounts of LTE4, the
      recovery of LTE4 added to the urine specimen was less than 120%. The
      concentration of LTE4 in urine from normal healthy subjects was 48.0+/-15.3 pg/mg
      creatinine (n=15).

PMID- 9188838
TI  - Determination of N(G),N(G)-dimethylarginine in human plasma by high-performance
      liquid chromatography.
AB  - N(G),N(G)-Dimethylarginine (asymmetric dimethylarginine, ADMA) can be directly
      separated and measured from deproteinized human plasma using o-phthaldialdehyde
      mercaptoethanol (OPA reagent) as a fluorogenic reagent by reversed-phase high
      performance liquid chromatography. The mean recovery of ADMA was over 96% and the
      inter- and intra-assay coefficients of variation of amounts were lower than 3.80%
      and those of retention time were below 0.37% for five runs. The detection limit
      of the assay is 1 pmol when the signal-to-noise ratio is 3:1. It was observed
      that the concentration of ADMA was significantly elevated in plasma of patients
      with pregnancy induced hypertension (PIH) in contrast to healthy pregnant women.

PMID- 9188839
TI  - Determination of albuterol in plasma after aerosol inhalation by gas
      chromatography-mass spectrometry with selected-ion monitoring.
AB  - Albuterol is a beta2-adrenergic agonist commonly used as a bronchodilator for the
      treatment of patients with asthma. We have developed an assay to determine plasma
      levels as low as 50 pg/ml of albuterol by gas chromatography-mass spectrometry
      (GC-MS). This assay utilizes isotopically labeled albuterol ([13C]albuterol) as
      an internal standard. In this assay albuterol and the internal standard are
      recovered from 1 ml of plasma using solid-phase extraction. The samples are then
      derivatized to trimethylsilyl ethers using N,O-bis(trimethylsilyl)trifluoro
      acetamide with 1% trimethylchlorosilane. The samples are then analyzed by GC-MS
      with selected-ion monitoring (SIM) for the ions m/z 369.15 and 370.15. The method
      has been validated for a concentration range of 50-10000 pg/ml in plasma.

PMID- 9188840
TI  - Determination of erythromycin concentrations in rat plasma and liver by high
      performance liquid chromatography with amperometric detection.
AB  - A simple method for the quantitative determination of erythromycin (EM)
      concentrations in rat plasma and liver by high-performance liquid chromatography
      with amperometric detection was developed. EM was extracted from 200 microl of
      plasma or liver homogenate sample under sodium hydroxide alkaline conditions with
      tert.-butyl methyl ether. Oleandomycin was used as an internal standard. The
      recovery rate of EM was up to 100%. The detector cell potential for the oxidation
      of EM was +1100 mV. The calibration curves were linear over the concentration
      ranges 0.1-20.0 microg/ml for plasma and 0.5-100.0 microg/g for liver. The method
      was applied to the determination of the plasma and liver concentrations of EM in
      rats after intravenous administration (50 mg/kg dose). The method presented here
      has proved to be of great use for the investigation of the pharmacokinetic
      characteristics of EM in small animals such as rats.

PMID- 9188841
TI  - Determination of piracetam in human plasma by capillary electrophoresis.
AB  - A capillary electrophoresis (CE) procedure has been developed for the
      determination of piracetam in human plasma. Analyses were performed on an
      uncoated silica capillary using borax buffer modified with the addition of alpha
      cyclodextrin. The detection was UV, operated at 200 nm. The detection limit of
      the authentic samples was 1 microg/ml. The calibration curve was linear over a
      range of 4 to 24 microg/ml (r=0.997). Inter-assay R.S.D. was below 9.3%. The
      described method has been successfully applied to the quantitative determination
      of piracetam in human plasma and should be useful for clinical and
      bioavailability investigations.

PMID- 9188842
TI  - Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a
      plasmacytoma x fibroblast environment: implications for dysregulation of
      translocated c-myc.
AB  - Regulation of immunoglobulin heavy chain (IgH) gene expression is controlled by a
      B cell-specific promoter, intronic enhancer and additional B cell-specific
      enhancer elements identified recently in the 3' end of the IgH locus. One of the
      latter elements, the IgH 3' enhancer, is of particular interest: (1) it is B cell
      specific and active only in late B cell development; (2) in rodent plasmacytomas
      and in some human Burkitt's lymphomas it is part of a locus control region (LCR)
      that is involved in deregulation of the c-myc oncogene as a result of
      translocation into the IgH locus; and (3) it has been implicated in the
      mechanisms that control Ig gene class switch recombination. We have used a
      somatic cell hybridization approach to genetically analyse regulation of the
      activity of the IgH 3' enhancer. When mouse MPC11 plasmacytoma cells, in which
      the IgH 3' enhancer is active, are fused with fibroblasts, Ig expression is
      extinguished at the level of transcription. Here we show that in a MPC11
      plasmacytoma x fibroblast environment, the IgH 3' enhancer is transcriptionally
      inactive. Furthermore, we demonstrate that binding of several B cell-specific
      transcription factors, essential for IgH 3' enhancer activity, is lacking, which
      may explain 3' enhancer inactivity, although the binding of repressors cannot be
      excluded. Moreover, the high expression level of c-myc, characteristic of the
      parental MPC11 cells carrying the t(12;15) translocation, is down-regulated in
      the hybrids to that in unfused fibroblasts. Therefore, inactivation of the IgH 3'
      enhancer is a multifactorial process affecting several transcription factors that
      control the cell-specific and developmental activity of the enhancer.

PMID- 9188843
TI  - Sequence and structure specific antibodies from phage display libraries.
AB  - A large combinatorial phage display library was panned against five nucleic acid
      antigens, calf thymus DNA, poly[d(GC)], poly[d(AT)], poly(dA) x poly(dT) and
      poly(rA) x poly(dT). After the third and fourth rounds of panning, many positive
      clones were selected against poly[d(GC)], poly(dA) x poly(dT) and poly(rA) x
      poly(dT). The specificity of these antibodies was tested by both direct and
      competitive solid phase radioimmune assays. All the clones derived from panning
      with poly[d(GC)] were non-specific and bound to all nucleic acids. The poly(rA) x
      poly(dT) derived clones were specific for single-stranded nucleic acids, with
      some sequence preferences, and the poly(dA) x poly(dT) derived clones showed
      considerable specificity for this antigen. The sequences of these phage-derived
      antibodies showed no similarities with DNA-binding antibodies from other sources.
      Even after six rounds of panning no positive clones were detected which bound to
      poly[d(AT)] and after seven rounds only two were derived from panning with calf
      thymus DNA. Therefore, sequence- and structure specific antibodies can be
      recovered from phage display libraries but not all sequences may be represented
      in the repertoire.

PMID- 9188844
TI  - The MHC class II-restricted T cell response of C57BL/6 mice to human C-reactive
      protein: homology to self and the selection of T cell epitopes and T cell
      receptors.
AB  - The T cell response of C57BL/6 mice to human C-reactive protein (hCRP), an
      inducible acute phase protein, was analysed. Two I-A(b)-restricted epitopes at
      positions 79 95 (epitope A) and 87-102 (epitope B) were identified using a panel
      of CD4+ T cell clones. Human C-reactive protein shares considerable homology with
      mouse C-reactive protein and mouse serum amyloid P component. Interestingly, the
      two epitopes map to the region of lowest homology between human CRP and its mouse
      homologues. Human CRP-specific T cell clones express a restricted T cell receptor
      (TCR) repertoire, both with regard to usage of TCR germline gene segments (V
      alpha, J alpha, V beta, J beta) and certain TCR alpha beta combinations.
      Therefore, epitope-A specific clones preferentially use TCR V beta8.3 and V
      alpha3 J alpha15 V beta8.3-J beta2.3 and epitope-B specific clones use V beta2
      and V alpha1-J alpha24/30-V beta2. This bias is even more pronounced when TCR
      usage is correlated with epitope fine specificity. A role for homology of hCRP to
      self components in selecting these particular T cell epitopes and TCR is
      discussed.

PMID- 9188845
TI  - Structural analysis of class I MHC molecules: the cytoplasmic domain is not
      required for cytoskeletal association, aggregation and internalization.
AB  - The role of the cytoplasmic domain in a variety of the functional activities of
      class I MHC molecules has not been documented. To address this question, Jurkat
      cells were transfected with genes for either native class I MHC molecules or
      constructs in which all but four cytoplasmic amino acids were deleted. Antibody
      induced aggregation and internalization of class I MHC molecules were examined by
      flow cytometry, and cytoskeletal association was determined by analysing the
      detergent-resistant fraction of FITC-labeled mAb to class I molecules. The
      results indicate that the truncated class I MHC molecules are comparable to
      native class I MHC molecules in the ability to move in the plane of the membrane
      and aggregate, to associate with the cytoskeleton and to undergo mAb-induced
      internalization at 37 degrees C. Thus, the cytoplasmic domain of class I MHC
      molecules is not required for these functional activities.

PMID- 9188846
TI  - Cross-linking CTX, a novel thymocyte-specific molecule, inhibits the growth of
      lymphoid tumor cells in Xenopus.
AB  - CTX, a new Xenopus Ig superfamily molecule present on some cortical thymocytes
      and lymphoid tumor cells, is expressed at the cell surface under six differently
      glycosylated isoforms as shown by two-dimensional gel analysis and by endo F
      glycosidase treatment. Following chemical cross-linking before
      immunoprecipitation, a large fraction of surface CTX forms non-covalently linked
      dimers at the cell surface. This finding, which is consistent with the presence
      of a J segment with diglycine beta bulge in the V region of the molecule,
      suggests that this dimer has the same conformation as a T-cell receptor (TCR) or
      an Ig molecule. The V8 digest patterns of the monomers and dimers are identical.
      While this suggests that the dimer is a homodimer of two CTX chains, it does not
      distinguish whether each CTX chain is encoded by the same or different gene loci.
      When tumor cells were added to culture wells that had been coated with the anti
      CTX monoclonal antibody X71, 30-50% underwent rapid (within 30 min) morphological
      changes followed by growth inhibition as determined by a decrease in thymidine
      incorporation and by direct cell counting. No apoptosis, calcium flux or external
      calcium requirement was noted after cross-linking of CTX. These results suggest
      that CTX can function as a receptor, and that its interaction with a ligand
      influences the control of cell proliferation through a signalling pathway that is
      distinct from the TCR machinery.

PMID- 9188847
TI  - Peptide binding to mixed isotype Abeta(d)Ealpha(d) class II histocompatibility
      molecules.
AB  - Previous studies have demonstrated that mixed isotype A beta(d) E alpha(d)
      molecules are expressed in transfected cell lines and that the level of
      expression is very low in normal B cells from H-2(d) mice. T-cell responses
      restricted by A beta(d) E alpha(d) are induced in H-2(d) mice immunized with the
      synthetic peptides YL2 and FL2 or with sperm whale myoglobin, despite the low
      concentration of mixed isotype molecules expressed on antigen-presenting cells.
      In the present study, the peptide binding behavior of A beta(d) E alpha(d) was
      investigated. A peptide from the cytoplasmic domain of invariant chain, I(1-18),
      was observed to bind with high affinity to purified A beta(d) E alpha(d). Binding
      was optimal at pH 5, indicating that these molecules prefer to bind peptide in
      the acidic environment of endosomal compartments similar to other murine class II
      proteins. YL2 and FL2 bind to A beta(d) E alpha(d) with slightly lower affinity.
      The selective restriction of YL2- and FL2-specific T cells to mixed isotype
      molecules was accounted for by the observation that these peptides do not bind to
      either I-E(d) or I-A(d). By contrast, myoglobin peptides bind to both parental
      and mixed isotype molecules. None of the A beta(d) E alpha(d)-restricted peptide
      determinants bind to A beta(d) E alpha(d) with extremely high affinity. Thus it
      is unlikely that these peptides occupy an unusually high fraction of mixed
      isotype molecules during antigen presentation in vivo. It is more likely that the
      presence of a subpopulation of high-affinity T cells capable of being stimulated
      by very low concentrations of A beta(d) E alpha(d)/peptide complexes is
      responsible for the unusual A beta(d) E alpha(d)-restricted response observed
      with some antigens.

PMID- 9188848
TI  - On the immunogenic properties of retro-inverso peptides. Total retro-inversion of
      T-cell epitopes causes a loss of binding to MHC II molecules.
AB  - Retro-inversion is considered an attractive approach for drug and vaccine design
      since it provides the modified peptides with higher resistance to proteolytic
      degradation. We therefore investigated in detail the effect of retro-inversion on
      the immunological properties of synthetic peptides. We have synthesized retro
      inverso analogues of MHC II restricted peptides that thus contained the correct
      orientation of the side chains but an inverse main chain. Retro-inversion made
      the peptides unable to compete in I E(d) or I A(d) binding tests, demonstrating a
      very low, if any, capacity to bind to MHC II molecules. These results confirm
      previous structural data that hydrogen bonds between residues of MHC II molecules
      and the main chain of antigenic peptides play a major interacting role. In vito
      experiments further showed that retro-inversion of a T-cell epitope causes its
      inability to either sustain in vitro T-cell stimulation or to prime specific T
      cells. Moreover, the retro-inverso peptide was not recognized by antibodies
      raised against the native peptide and did not elicit antibodies when injected
      into BALB/c mice. Retro-inverso peptides appear to be poor immunogens as a result
      of their weak capacity to bind to MHC II molecules. As an advantage, they are not
      expected to trigger undesirable humoral responses such as hypersensitivity or
      allergic disease. These results also provide a molecular explanation regarding
      the weak immunogenicity of D-amino acids containing polypeptides.

PMID- 9188849
TI  - Cooperative effects of mutations in a recombinant Fab on the kinetics of antigen
      binding.
AB  - Recombinant Fabs, 57P and 174P, recognizing peptide 134-151 of the coat protein
      of tobacco mosaic virus, differ by 15 amino acid changes in the sequence of their
      variable region. Kinetic analysis using BIAcore showed that they recognized five
      peptide variants in the same ranking order, but that Fab 174P consistently
      dissociated faster from the peptides compared to Fab 57P. In order to identify
      amino acid substitutions that are responsible for differences in dissociation
      rates of the two Fabs, six hybrid Fabs have been constructed by exchanging three
      DNA segments. Four single and five multiple mutants were obtained by site
      directed mutagenesis. All Fabs recognized variant peptides in a similar ranking
      order. The high precision of biosensor measurements made it possible to detect
      small contributions to dissociation kinetics of at least five substitutions, as
      well as the presence of small-magnitude non-additive effects of multiple
      substitutions. Our results demonstrate the cooperative influence on dissociation
      kinetics of amino acid residues located away from each other and away from the
      Fab combining site.

PMID- 9188850
TI  - Multiple transcripts of the murine immunoglobulin epsilon membrane locus are
      generated by alternative splicing and differential usage of two polyadenylation
      sites.
AB  - The human C epsilon gene produces a number of alternatively spliced heavy chain
      transcripts of which some encode functional IgE isoforms. We now show that
      differentially processed epsilon mRNA variants also exist in the mouse and are
      generated by differential polyadenylation and alternative splicing of primary
      epsilon chain transcripts. The two poly(A) sites of the mouse membrane
      transcripts were identified in the present study by RACE-PCR analysis. The first
      poly(A) site is located 743 nt downstream from the beginning of the second
      membrane exon (M2) and contains the same non-consensus AGTAAA signal sequence as
      the single poly(A) site of the human membrane transcripts. The second poly(A)
      site is located almost 500nt further downstream and is characterized by an AAGAAA
      hexamer. This poly(A) site contains a (G+T) rich element downstream to the site
      of cleavage and polyadenylation and is preferentially utilized by the membrane
      epsilon transcripts. Additional diversity of epsilon transcripts is generated by
      alternative splicing between the last constant region exon (CH4) and the two
      membrane exons (M1 and M2). The alternatively spliced transcripts include two
      variants that skip the first membrane exon and encode epsilon heavy chains that
      lack the transmembrane domain. The third variant is generated by splicing to an
      internal site in M2 and codes for a membrane isoform that is 10 amino acids
      shorter in the cytoplasmic domain than the classical membrane IgE. Although
      little amino-acid sequence homology exists between the murine epsilon chain
      isoforms and their human counterparts, the pattern of splicing is rather
      conserved between the two species.

PMID- 9188851
TI  - Immunological effects of an arginine side chain contaminating synthetically
      prepared peptides.
AB  - The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective
      group coupled to arginine to mask the omega-nitrogen, in order to protect the
      guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl
      (Fmoc) procedure (Walker, 1994). This group is removed at the completion of
      peptide synthesis; however, the cleavage process can be incomplete. We have found
      that animals injected with a mixed population of pure, i.e. unmodified, and Mtr
      containing MBP peptides have an immunodominant humoral response to the Mtr
      bearing peptide. This response is dependent on the characteristics of the MBP
      peptide involved. For two MBP peptides, the Mtr-containing peptide had increased
      binding to antibody over pure peptide. For two other peptides, only the Mtr
      containing peptide bound antibody while the unmodified peptide did not. In a
      separate system involving a polyclonal response to an unrelated peptide from
      beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident.
      These results provide further evidence that a small side chain on a single amino
      acid in a peptide can markedly alter the immunogenicity and antigenicity of that
      peptide for antibody reactivity. This evidence emphasizes the need for a critical
      awareness of each component of peptide synthesis and its potential to alter the
      immunoreactivity of the final product.

PMID- 9188852
TI  - Myc activation of cyclin E/Cdk2 kinase involves induction of cyclin E gene
      transcription and inhibition of p27(Kip1) binding to newly formed complexes.
AB  - Induction of the Myc-oestrogen receptor fusion protein (MycER) by 4-OH-tamoxifen
      (OHT) leads to the activation of Cyclin E/Cyclin-dependent kinase 2 (CycE/Cdk2)
      complexes followed by the induction of DNA synthesis. As CycE/Cdk2 activity is
      essential for G1/S transition, we have investigated the mechanism by which Myc
      can activiate CycE/Cdk2. Our results suggest that this activation may involve at
      least two Myc-dependent steps: the induction of cyclin E gene transcription
      followed by accumulation of cyclin E mRNA in a protein synthesis-independent
      manner and the inhibition of p27(Kip1) association with CycE/Cdk2 complexes
      containing newly synthesised CycE. As a consequence phosphorylation of CycE-bound
      Cdk2 by cyclin activating kinase (CAK) is accelerated. We propose a model in
      which the active newly synthesised CycE/Cdk2 complexes trigger a positive feed
      back mechanism to activate preexisting complexes through phosphorylation
      dependent p27(Kip1) release.

PMID- 9188853
TI  - Disregulation of mitotic checkpoints and regulatory proteins following acute
      expression of SV40 large T antigen in diploid human cells.
AB  - SV40 large T antigen (T) inactivates the tumor suppressor proteins p53 and pRb,
      and can induce cells to enter DNA replication at inappropriate times. We show
      here that T also compromises three cell cycle checkpoints that regulate the entry
      into and exit from mitosis. Human diploid fibroblasts infected with a retrovirus
      expressing T displayed an attenuated radiation-induced mitotic delay, were more
      susceptible to chemical-induced uncoupling of mitosis from the completion of DNA
      replication, and were more likely to exit mitosis and rereplicate their DNA when
      mitotic spindle assembly was inhibited. Consistent with altered mitotic
      checkpoint control, cells expressing T displayed elevated protein levels and/or
      associated activities of the mitotic regulatory proteins cyclin A, cyclin B,
      Cdc25C and p34(cdc2). These changes in mitotic control were evident within 5-10
      population doublings after retroviral infection, indicating a direct effect of T
      expression. Cells acutely infected with the T-expressing retrovirus suffered
      numerical and structural chromosome aberrations, including increases in
      aneuploidy, dicentric chromosomes, chromatid exchanges and chromosome breaks and
      gaps. These findings indicate that T rapidly disrupts mitotic checkpoints that
      help maintain genomic stability, and suggest mechanisms by which T induces
      chromosome aberrations and promotes the immortalization and neoplastic
      transformation of human cells.

PMID- 9188854
TI  - Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and
      cyclin E/cdk 2 complexes.
AB  - P130 shares structural and functional homology with pRb and p107. One property
      common to p107 and p130, but not to pRb, is the ability to stably interact with
      cyclin A/cdk2 and cyclin E/cdk2 complexes in vitro and in vivo. Using GST-p130
      fusion proteins representing various regions of p130, baculovirus-produced cyclin
      A/cdk2 and cyclin E/cdk2 complexes were found to interact with residues within a
      part of p130 known as the spacer region. Cyclin E was able to bind the p130
      spacer region in the presence or absence of cdk2 whereas cyclin A binding was
      dependent upon the presence of cdk2. The smallest p130 fusion protein sufficient
      to interact with cyclin A/cdk2 or cyclin E/cdk2 complexes contained p130 amino
      acids 652-698 and deletion of p130 amino acids 680-682 abolished binding to both
      of the cyclin/cdk2 complexes. When overexpressed in C33A cells, a p130 mutant
      containing a deletion of amino acids 620-697 was unable to form complexes with
      either cyclin A or cyclin E. This p130 mutant was at least as active as wild type
      p130 in suppressing the growth of G418 resistant colonies when overexpressed in
      C33A or SAOS-2 cells.

PMID- 9188855
TI  - Characterization of the mitotic phase pRb-directed protein phosphatase activity.
AB  - We have previously reported on the M-phase specific dephosphorylation of pRb and
      identified a type 1 serine/threonine protein phosphatase (PP1) as the enzyme
      mediating pRb dephosphorylation. In this report, we have characterized the pRb
      directed phosphatase activity found in mitotic cells with respect to dose
      dependence and demonstrate that the pRb isoform conversion detected in vitro
      mirrors the pRb isoform conversion which occurs during mitosis of intact cells.
      Cell fractionation and PP1 catalytic subunit isolation studies support the notion
      that the pRb-directed phosphatase activity involves subpopulations of PP1
      catalytic subunits. Coprecipitation studies revealed that PP1 can form a complex
      with hypophosphorylated pRb which was converted from the hyperphosphorylated form
      in mitotic cell extracts. Taken together with data from previous reports in the
      literature, a model for the regulation of PP1 activity towards pRb during mitotic
      exit is proposed.

PMID- 9188856
TI  - Activated ras and ret oncogenes induce over-expression of c-met (hepatocyte
      growth factor receptor) in human thyroid epithelial cells.
AB  - Hepatocyte Growth Factor (HGF) receptor, encoded by the protooncogene c-met, is
      overexpressed in many human tumours, including those of thyroid epithelium. The
      absence in most cases of any primary structural abnormality of the met gene
      suggests that overexpression is secondary to mutation of other gene(s). To test
      this hypothesis we investigated the effect on met expression of two activated
      oncogenes known to play a major role in thyroid oncogenesis, ras and ret. To
      minimize the possibility of unknown co-operating events, we introduced these
      genes directly into normal human thyrocytes in primary culture using amphotropic
      retroviral vectors and assessed met expression as early as possible in the
      resulting epithelial colonies. Double immunofluorescence revealed expression of
      met protein, strictly localized to cells expressing the mutant ras and ret
      vectors, expression in background normal cells being barely detectable. In
      contrast, colonies induced to proliferate at a comparable rate by a vector
      expressing SV40 T showed no increase in met expression. To permit quantitation by
      Western blotting we also extended these findings to a thyroid cell line (R18)
      containing a zinc-inducible mutant ras gene. Induction of the oncogene led to a
      fourfold increase in met protein expression. We conclude that overexpression of
      met is induced by activation of the ras or ret signalling pathway and not simply
      by deregulation of the cell cycle per se. The data suggest that the proliferative
      advantage conferred by these oncogenes may be in part due to the resulting
      sensitization of tumour epithelium to paracrine HGF secreted by stromal cells.

PMID- 9188858
TI  - Phosphorylation and high level expression of Fra-2 in v-src transformed cells: a
      pathway of activation of endogenous AP-1.
AB  - Chicken embryo fibroblasts (CEF) transformed with v-src were previously reported
      to revert to normal phenotype after the introduction of dominant-negative mutants
      of Fos or Jun, indicating that endogenous AP-1 activity is essential for the
      cellular transformation. The major changes in the expression levels of fos and
      jun family genes induced by v-src were the elevation of fra-2 and c-jun
      transcripts. We show here that extensive phosphorylation of the AP-1 component
      Fra-2 is a major qualitative change in v-src transformed CEF and that several Ser
      and Thr residues in a C-terminal region of Fra-2 (amino acids 266-323) are
      phosphorylated specifically. The induced kinase activity was detected at the
      position of 42 kDa by in gel kinase assay using the Fra-2 C-terminal region as a
      substrate, and it was identified as chicken ERK2. JNK1 and JNK2, other members of
      the MAP kinase family, were not significantly activated in v-src transformed CEF
      and Fra-2 was not a good substrate for JNKs. fra-2 promoter analysis indicated
      that this promoter activity is elevated in v-src transformed CEF via two AP-1
      binding sites and CRE-like sequence. We propose that phosphorylation of Fra-2 by
      ERK2 converts it from an inefficient transcriptional activator to an active one
      and further that fra-2 expression is autoregulated in response to the
      phosphorylation status of its gene product.

PMID- 9188857
TI  - Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila
      discs large (dlg) tumor suppressor protein interacts with the APC protein.
AB  - We have cloned a cDNA for a novel human homolog of the Drosophila discs large
      (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig).
      Northern blot analysis revealed that the gene is highly expressed in neuronal and
      endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid
      mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that
      the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE
      dlg antibody showed that the protein tended to be expressed in non-proliferating
      cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of
      the heart muscles, and the prickle and functional layer cells of the esophageal
      epithelium. Proliferative cells, including various cultured cancer cell lines and
      basal cells in the esophageal epithelium, showed little expression of the NE-dlg
      protein. In addition, yeast two-hybrid screening and in vitro binding assays
      revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC
      tumor suppressor protein. These data suggest that NE-dlg negatively regulates
      cell proliferation through its interaction with the APC protein.

PMID- 9188859
TI  - B-Myb function can be markedly enhanced by cyclin A-dependent kinase and protein
      truncation.
AB  - Transcription of the B-Myb gene is cell cycle regulated by an E2F-dependent
      mechanism and its product, B-Myb, is itself a transcription factor required for S
      phase entry. Previously, we have shown that B-Myb is specifically phosphorylated
      during S-phase and that similar modification to a less electrophoretically mobile
      form could be induced by baculovirus-expressed cyclin A/Cdk2 kinase. We report
      here that cyclin A-mediated phosphorylation of B-Myb is associated with a marked
      increase in transactivation function in U-2 OS cells. In contrast to previous
      studies, transactivation of the luciferase reporter was dependent upon Myb
      binding sites located upstream of the promoter. Enhancement of B-Myb activation
      function was also obtained by truncation of the C-terminus just downstream of a
      domain conserved in evolution. Potentiation of B-Myb activity by phosphorylation
      was not simply a consequence of overcoming the negative effect of the C-terminus,
      however, as the truncated protein was to a lesser extent also activated by cyclin
      A/Cdk2. Whereas wild-type B-Myb transactivation activity could not be potentiated
      by cyclin A/Cdk2 in NIH3T3 cells, the truncated protein was hyperactive. Finally,
      we showed that B-Myb synergises with cyclin A to promote U-2 OS cells into S
      phase.

PMID- 9188860
TI  - Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP
      signaling: a potential role for transcription factor NF-kappa B.
AB  - TCR-mediated activation of T cell hybridomas induces programmed cell death by a
      Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the
      absence or presence of transgenic Bcl-2, with anti-CD3 epsilon and forskolin, an
      activator of cAMP signaling, resulted in antagonism of Fas-dependent activation
      induced cell death that was always accompanied by selective downregulation of the
      nuclear levels of NF-kappa B p65-p50 (RelA-p50) transcription factor. Forskolin
      not only inhibited activation-induced cell death and NF-kappa B activation, but
      also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-kappa B
      p65 antisense oligonucleotide down-regulated nuclear levels of NF-kappa B,
      inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively,
      these finding demonstrate a potential role of NF-kappa B in the regulation of
      activation-induced apoptosis in T lymphocytes.

PMID- 9188861
TI  - BCL-6 is phosphorylated at multiple sites in its serine- and proline-clustered
      region by mitogen-activated protein kinase (MAPK) in vivo.
AB  - BCL-6 gene alterations have been observed in 27-45% of diffuse large B-cell
      lymphomas (DLBs) with chromosomal translocations at 3q27. The deregulated
      expression of normal BCL-6 protein caused by this chromosomal translocation is
      believed to be responsible for lymphomagenesis. Recently, we demonstrated that
      BCL-6 is expressed at high levels in germinal center B-cells as a 92-98 kDa
      nuclear protein in a constitutively phosphorylated form. In this study, we show
      that BCL-6 is phosphorylated by mitogen-activated protein kinase (MAPK) in vitro
      at the sites phosphorylated in vivo. These numerous phosphorylation sites were
      found to be located in its serine- and proline-clustered (SPC) region (amino
      acids-250-483). BCL-6 phosphorylation significantly increased in Ramos cells
      following stimulation with 12-o-tetradecanoylphorbol-13-acetate (TPA) or BCL-6-
      and erk1-transfected COS-7 cells stimulated with epidermal growth factor (EGF),
      and the increase of phosphorylation was inhibited by MEK1 inhibitor, PD98059.
      Furthermore, we observed that BCL-6 was associated with MAPK in vivo and its SPC
      region was important for this association. These results suggest that the
      functions of BCL-6 are regulated by phosphorylation mediated by the MAPK
      signaling pathway.

PMID- 9188862
TI  - Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth
      factors, oncoproteins and hypoxia.
AB  - The vascular endothelial growth factor (VEGF) family has recently been expanded
      by the isolation of two additional growth factors, VEGF-B and VEGF-C. Here we
      compare the regulation of steady-state levels of VEGF, VEGF-B and VEGF-C mRNAs in
      cultured cells by a variety of stimuli implicated in angiogenesis and endothelial
      cell physiology. Hypoxia, Ras oncoprotein and mutant p53 tumor suppressor, which
      are potent inducers of VEGF mRNA did not increase VEGF-B or VEGF-C mRNA levels.
      Serum and its component growth factors, platelet-derived growth factor (PDGF) and
      epidermal growth factor (EGF) as well as transforming growth factor-beta (TGF
      beta) and the tumor promoter phorbol myristate 12,13-acetate (PMA) stimulated
      VEGF-C, but not VEGF-B mRNA expression. Interestingly, these growth factors and
      hypoxia simultaneously downregulated the mRNA of another endothelial cell
      specific ligand, angiopoietin-1. Serum induction of VEGF-C mRNA occurred
      independently of protein synthesis; with an increase of the mRNA half-life from
      3.5 h to 5.5-6 h, whereas VEGF-B mRNA was very stable (T 1/2>8 h). Our results
      reveal that the three VEGF genes are regulated in a strikingly different manner,
      suggesting that they serve distinct, although perhaps overlapping functions in
      vivo.

PMID- 9188863
TI  - Alternative splicing of the human CDC25B tyrosine phosphatase. Possible
      implications for growth control?
AB  - CDC25B2, a protein tyrosine phosphatase closely related to the putative CDC25B
      oncogene, was identified in a Burkitt lymphoma cDNA library. CDC25B2 differs from
      CDC25B by a 14 residue insertion and a 41 residue deletion, which are both
      located in the amino-terminal region of the protein, upstream of the catalytic
      domain. Examination of the genomic sequence revealed that CDC25B1 (formerly B)
      and CDC25B2 are splice variants of the same gene. A third variant, CDC25B3, that
      carries both the 14 and the 41 residue sequences was also identified in the same
      cDNA library. All three variants were detected in a panel of human primary
      culture and cell lines, although at different levels. In primary fibroblasts and
      in HeLa cells the CDC25B expression is cell cycle regulated, reaching a maximum
      in G2-phase. In vitro, CDC25B1 phosphatase is slightly more active than CDC25B2
      and B3. However, episomal overexpression of the three CDC25B variants in fission
      yeast reveals that in vivo, CDC25B2 is largely more active than either B1 or B3
      (B2>B3>B1) both to complement a thermosensitive S pombe CDC25 activity and to act
      as a mitotic inducer. Alternative splicing of CDC25B may therefore contribute to
      the control of cell proliferation.

PMID- 9188864
TI  - Detection of streptococcal class I M protein in psoriasis by confocal
      immunofluorescent microscopy.
AB  - Epidemiological evidence implicates Streptococcus pyogenes (group A) infection as
      a common triggering stimulus for psoriasis. Unequivocal demonstration of
      streptococcal antigens in psoriatic skin has been difficult due to cross-reactive
      antigens in both normal human tissue and group A streptococci, which complicate
      immunohistological analysis. In this study cryostat sections of involved
      psoriatic skin were stained with monoclonal antibody 111-15504 to group A
      streptococci. The epitope recognized by this antibody was found to be specific
      for group A streptococci and is associated with class I M protein. Streptococcal
      antigens were found in the dermal papillae and epidermis of psoriatic skin
      lesions of 20 out 38 patients. These findings indicate that specific S. pyogenes
      antigen, associated with class I M protein, is often present in psoriatic
      lesions. Such an antigen, originating from focal infection elsewhere could be
      responsible for T-lymphocyte inflammatory responses triggering the development of
      psoriatic lesions.

PMID- 9188865
TI  - A study of coagulation and anti-endothelial antibodies in idiopathic livedo
      reticularis.
AB  - Livedo reticularis is associated with collagen vascular diseases and other vaso
      occlusive disorders in a substantial number of cases. In the remaining cases the
      cause of livedo reticularis is still unknown. (i.e., idiopathic). We sought to
      determine a possible causal relationship between idiopathic livedo reticularis
      and autoimmune factors associated with the coagulation system, including
      antiendothelial cell antibodies. Nine patients with idiopathic livedo reticularis
      were studied. All patients were found to have normal platelet count, fibrinogen
      levels, and prothrombin and activated partial thromboplastin times, as well as
      negative results for Venereal Disease Research Laboratory and D-timer tests.
      Anticoagulant activity was detected in 2 patients: one had positive results of
      thromboplastin titration index and Russell's viper venom test, as well as
      increased levels of anticardiolipin antibodies and anti-endothelial cell
      antibodies; the other has positive thromboplastin titration index, mildly
      increased levels of anti-endothelial cell antibodies, and markedly increased
      levels of antinuclear antibodies. A third patient had mildly increased levels of
      anti-endothelial cell antibodies alone, and a fourth patient had mildly increased
      levels of antinuclear antibodies only. The clinical outcome was uneventful in all
      of the patients during an 18-month follow-up period. These findings suggest
      involvement of autoimmune factors associated with the coagulation system in some
      patients with idiopathic livedo reticularis, whose clinical significance remains
      to be determined.

PMID- 9188866
TI  - T-cell receptor V beta expression is restricted in dermatitis herpetiformis skin.
AB  - An infiltrate of T-cells is found in lesional dermatitis herpetiformis skin, but
      the role of these cells in the pathogenesis of the skin lesions is unknown. The
      purpose of this study was to examine T-cell receptor V beta expression in skin
      biopsies taken from patients with dermatitis herpetiformis. Expression of eleven
      T-cell receptor V beta families in biopsies obtained from 10 patients was
      examined by immunoperoxidase staining and compared simultaneously with peripheral
      blood lymphocytes. Over-representation of V beta 2 (p < 0.02), V beta 5.2/5.3 (p
      < 0.01) and V beta 5.3 (p < 0.05) was found in lesional dermatitis herpetiformis
      skin compared with peripheral blood lymphocytes. These results suggest that
      recognition of an antigen(s) or superantigen is involved in the pathogenesis of
      dermatitis herpetiformis skin lesions.

PMID- 9188867
TI  - Immunoblot analysis of autoantigens in localized pemphigoid and pemphigoid
      nodularis.
AB  - We analyzed circulating antibodies in sera from patients with localized
      pemphigoid and pemphigoid nodularis, two variants of bullous pemphigoid, by means
      of western immunoblotting of human epidermal extracts and the recombinant protein
      of NC16a domain of the 180 kD bullous pemphigoid antigen. NC16a domain is now
      considered to be the most pathogenic site of bullous pemphigoid. Compared with
      the results of typical bullous pemphigoid patients, localized pemphigoid sera
      detected the 180 kD bullous pemphigoid antigen less frequently, and sera from
      both localized pemphigoid and pemphigoid nodularis showed a lower end point of
      titer of antibodies to NC16a domain. These results suggest that atypical clinical
      features of the two bullous pemphigoid variants may be related with low titer of
      autoantibodies to 180 kD bullous pemphigoid antigen, particularly to NC16a
      domain.

PMID- 9188868
TI  - In situ expression and serum levels of tumour necrosis factor alpha receptors in
      patients with lichen planus.
AB  - In lichen planus (LP), an inflammatory skin disease of unknown origin, adhesion
      molecules and their ligands combined with the local and systemic release of
      various cytokines are fundamental in regulating inflammation. Therefore, we
      investigated the expression of tumour necrosis factor alpha receptor (TNF-R) I
      and II in lesional skin of 15 patients suffering from acute eruptive LP by means
      of immunohistochemistry. In addition, the serum levels of their soluble forms
      (sTNF-R) were measured by enzyme-linked immunosorbent assay (ELISA), compared
      with those of healthy volunteers (n = 10) and correlated with the in situ
      inflammatory response. In contrast to healthy controls, LP patients showed
      significantly increased serum levels of sTNF-RI as well as sTNF-RII (p < 0.02).
      These enhanced serum titres were correlated with a prominent expression of TNF-RI
      on lesional keratinocytes (basal > suprabasal) and of both receptors on skin
      infiltrating lymphocytes. Our data suggest an important role of the TNF
      ligand/receptor interactions in the induction and/or perpetuation of the
      pathogenetical and apoptotic events in LP.

PMID- 9188869
TI  - Histopathological findings, viral DNA distribution and lymphocytic
      immunophenotypes in vesicular and papular types of herpes zoster.
AB  - The characteristics rash of herpes zoster begins as erythematous macules and
      papules, progressing to vesicles within 12-24 h. Patients with persistent papules
      without vesicular change are occasionally found. Our aim was to elucidate
      differences in vesicular and papular types of herpes zoster. Biopsy specimens
      from 21 patients were examined by an in situ hybridization method to observe
      viral distribution, and lymphocytic immunophenotypes were evaluated
      immunohistochemically. There was no differences in cell-mediated immunity or
      immunophenotypes in lymphocytic infiltrates between vesicular and papular types
      of herpes zoster. DNA of varicella-zoster virus was detected in the epidermis and
      hair follicles in the vesicular type but was found in the pilosebaceous unit in
      the papular type. This indicates that the appearance of clinical types of herpes
      zoster depends on the infected site of varicella-zoster virus in the tissue.

PMID- 9188870
TI  - Ultrastructure of murine dermis following topical application of the vitamin D3
      analogue KH-1060.
AB  - The aim of this study, was to observe the effects of KH-1060, a new vitamin D3
      analogue, on the dermis of hairless mice by electron microscopy. KH-1060 (0.2
      micrograms/ml in isopropanol) or KH-1060 following betamethasone 17-valerate (2
      mg/ml in isopropanol) was applied topically to the backs of hairless mice for 4
      weeks. KH-1060 increased the number of dermal fibroblasts, the cytoplasm of which
      was dominated by secretory components. Mast cells contained normal mature
      granules and degranulated after disintegration. No extrusion of non-disintegrated
      granules was seen. Collagen fibrils were thickened and increased in number;
      however the content of type I collagen in the fibrils did not increase.
      Glycosaminoglycan figures appeared distinct. KH-1060 prevents betamethasone
      induced changes in collagen fibrils and glycosaminoglycans, while no prevention
      was seen for mast cells.

PMID- 9188871
TI  - Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum
      chymotryptic enzyme in vitro.
AB  - Interleukin 1 beta (IL-1 beta) is produced as a biologically inactive 31 kD
      precursor, which is converted to the active 18 kD form by proteolytic processing.
      Keratinocytes express IL-1 beta but not the active form of the specific IL-1 beta
      converting enzyme (ICE). We have recently presented evidence that IL-1 beta
      activation in human epidermis occurs via an alternative mechanism involving
      hitherto unknown proteases. We asked whether stratum corneum chymotryptic enzyme
      (SCCE), which is a serine protease specifically expressed in keratinizing
      squamous epithelia, can act as an IL-1 beta activator in vitro. Recombinant human
      pro-IL-1 beta was incubated with recombinant SCCE, and the reaction products were
      characterized as regards molecular size and ability to induce expression of E
      Selectin in human umbilical cord endothelial cells. SCCE caused degradation of
      pro-IL-1 beta and the accumulation of a component with electrophoretic mobility
      slightly lower than recombination mature IL-1 beta. Whereas incubation mixtures
      with pro-IL-1 beta which had been incubated in the absence of SCCE, or with SCCE,
      which had been incubated in the absence of pro-Il-1 beta, did not induce
      expression above baseline levels of E-Selectin, pro-Il1 beta which had been
      incubated with SCCE induced a significant increase in E-Selectin expression. This
      effect could be abolished by neutralizing antibodies to IL-1 beta, but not by
      antibodies to IL-1 alpha. In addition to IL-1 beta activation, SCCE also prepared
      to be able to catalyze a further degradation of IL-1 beta, leading to a loss of
      biological activity. We conclude that SCCE is a potential candidate for being
      responsible for IL-1 beta activation in human epidermis.

PMID- 9188872
TI  - Porokeratosis of Mibelli. Overview and review of the literature.
AB  - Porokeratosis of Mibelli is an uncommon dermatosis, which may be associated with
      immunosuppression and may undergo malignant transformation. Due to the wide range
      of clinical presentations, numerous classifications have evolved, resulting in
      some confusion. This article examines the classification and presentation of
      porokeratosis and, in particular, reviews the association with immunosuppression.

PMID- 9188873
TI  - Comparison of the analgesic effect of EMLA cream and EMLA patch on normal skin
      evaluated with laser-induced pain stimuli.
AB  - In the present study the onset, duration and efficacy of the analgesic effect of
      EMLA patch compared to EMLA cream were investigated on the skin of the forearms
      of 12 healthy adults. EMLA patch and cream were applied for 30, 60 and 120 min.
      The pain threshold was determined 5 min after removal of the test substance,
      using high-energy argon laser stimuli, and thereafter every 30 min for 4 h. After
      120 min of application, both EMLA cream and EMLA patch ensured total analgesia.
      The clinical analgesic efficacy of EMLA patch was found equal to that of EMLA
      cream.

PMID- 9188874
TI  - The dermal type of erythema multiforme: a rare variant of Stevens-Johnson
      syndrome or cases of clinical misclassification?
AB  - Since 01.04.90 the Dokumentationszentrum schwerer Hautreaktionen (dZh) in
      Freiburg has registered cases of severe skin reactions like erythema exsudativum
      multiforme majus, Stevens-Johnson syndrome and toxic epidermal necrolysis in
      Germany. With the largest study so far of histological slides from patients
      included in this registry we were able to show that the epidermal type of
      erythema multiforme described by Orfanos et al. is the histopathological
      correlated of these severe skin reactions. Except two biopsies all of the
      specimens taken from the registered patients showed histological characteristics
      of this type of erythema multiforme. These two cases are now reported. Clinical
      data and photographic documentation did not prove authentic erythema multiforme.
      The lesions of both patients were described as atypical macules and papules;
      mucosal sites were only locally involved. Biopsies taken from the patients had
      the characteristics of the dermal type of erythema multiforme (Orfanos et al.).
      We conclude that histomorphological characteristics of the dermal type, in
      addition to an atypical clinical course, favour another diagnosis, such as
      multiforme-like eruption.

PMID- 9188875
TI  - Seasonal variation of skin pigmentation.
AB  - We measured skin pigmentation by skin reflectance monthly from May 1992 to April
      1993 in 36 healthy Caucasians. Pigmentation was measured at four UV-exposed sites
      at the forehead, the upper chest, the inside of the upper arm, and at the upper
      back. The pigmentation and UV sensitivity were simultaneously measured at UV
      protected buttock skin. The results showed a considerable seasonal variation for
      skin pigmentation at the UV-exposed sites. Buttock skin had a pigmentation and UV
      sensitivity that varied only marginally. We recommend that measurements of
      genetically controlled skin pigmentation and constitutive UV sensitivity should
      be performed at UV-unexposed skin on the buttocks, except in persons that expose
      this site to artificial or natural sunlight.

PMID- 9188876
TI  - Cutaneous infection due to Mycobacterium abscessus. A case report.
AB  - Erythematous nodular and ulcerating skin lesions occurred in a 56-year-old woman
      treated with chemotherapy and glucocorticosteroids for metastatic breast cancer.
      Subsequent culture yielded Mycobacterium abscessus, a facultative pathogen which
      exists as a saprophyte in the environment and rarely produces clinical disease in
      humans. This organism is usually relatively resistant to antituberculous as well
      as a number of other antimicrobial agents. On the basis of in vitro
      susceptibility results, treatment with clarithromycin and clofazimine was
      installed and resolution of the lesions initiated. This report emphasizes once
      again that one should investigate any new or unusual skin lesions in
      immunocompromised patients by histology and culture of biopsies, including
      cultures for acidfast organisms.

PMID- 9188878
TI  - A randomized double-blind comparison of the effects on systemic calcium
      homeostasis of topical calcitriol (3 micrograms/g) and calcipotriol (50
      micrograms/g) in the treatment of chronic plaque psoriasis vulgaris.
AB  - Calcitriol and calcipotriol are effective treatments for psoriasis, although the
      two have never been directly compared. We compared the efficacy and toxicity of
      each agent in 24 patients with moderately extensive chronic plaque psoriasis, who
      were randomized in double-blind fashion to apply 90 g per week of either
      calcitriol (3 micrograms/g) ointment or calcipotriol (50 micrograms/g) ointment
      over an 8-week period. Mean PASI in patients applying calcitriol fell from 13 to
      8.8 (p < 0.05) and in patients applying calcipotriol from 14.9 to 4.7 (p <
      0.005). The reduction was significantly greater in the calcipotriol-treated group
      (p < 0.05). There was a small increase in serum ionized calcium in the
      calcipotriol-treated group (from 1.21 mmol/L to 1.25 mmol/L, p < 0.05) but no
      effect on calcium homeostasis in the calcitriol group.

PMID- 9188877
TI  - Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK
      syndrome): a rare, autosomal recessive disorder of keratohyaline formation?
AB  - We report a 32-year-old man with an unusual combination of congenital ichthyosis,
      sclerosing palmoplantar keratoderma with pseudoainhum, and bizarre striate
      hyperkeratosis in the fixtures, but no systemic involvement. The condition, which
      improved on oral etretinate therapy, had not appeared previously in the family.
      On light microscopy the involved epidermis showed marked acanthosis with
      hypergranulosis and hyperkeratosis. Electron microscopy disclosed numerous large
      keratohyaline granules in superficial keratinocytes. The clinical picture and
      histology are virtually identical to those of a Spanish family suffering from an
      autosomally recessive skin disease of unknown etiology. We hypothesize that the
      condition is due to a genetic defect in the formation of keratohyaline granules.

PMID- 9188879
TI  - Subacute and chronic prurigo effectively treated with recombination interferon
      gamma: implications for participation of Th2 cells in the pathogenesis of
      prurigo.
AB  - Subacute and chronic prurigo is notoriously resistant to usual therapies. Four of
      five patients with a subacute or chronic form of prurigo responded well to daily
      intravenous injections of recombinant interferon-gamma (rIFN-gamma) (0.25-2 x
      10(6) Japan Reference Unit (JRU; 1 JRU roughly corresponds to 4 NIH units) daily,
      for 10-14 days). In one patient examined, the dermal portion of lesional skin
      before the treatment contained considerable amounts of mRNA for interleukin (IL)
      4, IL-5, and IL-10, indicative of infiltration of Th2 cells. Furthermore, the
      administration of rIFN-gamma selectively down-regulated mRNA for Th2 cytokines,
      IL-4 and IL-10 in peripheral blood mononuclear cells. These findings suggest that
      Th2 cells play a pathogenic role in these types of prurigo and that rIFN-gamma
      exerts its efficacy by inhibiting Th2 cells. Our pilot study suggests that the
      systemic administration of rIFN-gamma is a therapeutic alternative for the
      treatment of recalcitrant prurigo.

PMID- 9188880
TI  - Lesional mRNA expression of Th1 cytokines in adult T-cell leukemia/lymphoma.

PMID- 9188881
TI  - Anti-230 kDa circulating IgE in bullous pemphigoid: relationship with disease
      activity.

PMID- 9188882
TI  - Abnormal corneometric values of non-lesional plaque-type psoriatic skin.

PMID- 9188883
TI  - Long-term follow-up of toe-nail onychomycosis treated with terbinafine.

PMID- 9188884
TI  - The interaction between stratum corneum and dermatophytes in patients with
      chronic tinea pedis.

PMID- 9188885
TI  - Cycloheximide in dermatology.

PMID- 9188886
TI  - Extramammary Paget's disease associated with autoimmune hemolytic anemia.

PMID- 9188887
TI  - Syringocystadenoma papilliferum, basal cell carcinoma and trichilemmoma arising
      from nevus sebaceus of Jadassohn.

PMID- 9188888
TI  - Naevus comedonicus as dermatologic hallmark of occult spinal dysraphism.

PMID- 9188889
TI  - Alopecia syphilitica in a prepubertal girl.

PMID- 9188890
TI  - Higher herpes zoster infection frequency in right-handed patients and more
      frequent appearance in the left body side of females.

PMID- 9188891
TI  - Transient acantholytic dermatosis (Grover's disease) in a patient with gastric
      carcinoma.

PMID- 9188892
TI  - Lipo-prostaglandin E1 therapy for livedo reticularis with ulceration.

PMID- 9188893
TI  - Subungual fibro-osseous pseudotumor.

PMID- 9188894
TI  - Lymphoedema of the inner thighs in late pregnancy.

PMID- 9188895
TI  - Acute generalized exanthematous pustulosis induced by lansoprazole.

PMID- 9188897
TI  - Lymphangioma circumscriptum of the penis.

PMID- 9188896
TI  - Vulvar adenosis after diathermy treatment for condylomas.

PMID- 9188898
TI  - Predictors and dynamics of posttraumatic epilepsy.
AB  - OBJECTIVES: The goal of our study was to identify clinical, neurophysiological
      and neuroradiological variables in severe head trauma (SHT) with predictive value
      for posttraumatic epilepsy (PTE) and to evaluate the influence of each risk
      factor for the dynamics of epilepsy. MATERIALS AND METHODS: We systematically
      compared 57 PTE patients with 50 age and sex-matched control patients with SHT
      and no PTE. Mean follow-up was 8 years. RESULTS: Of all PTE-patients 68.5% had
      their first seizure within 2 years after the trauma. Significant risk factors for
      PTE were focal signs in the first examination (P < 0.01), missile injuries (P <
      0.01), frontal lesions (P < 0.01), intracerebral hemorrhage (P < 0.01), diffuse
      contusion (P < 0.01), prolonged posttraumatic amnesia (P < 0.001), depression
      fracture (P < 0.01) and cortical-subcortical lesions (P < 0.001). The combination
      of the last 3 variables conferred a particularly high risk for PTE (logistic
      regression analysis). Combined seizure pattern, high seizure frequency, AED
      noncompliance and alcohol abuse predicted poor seizure control. CONCLUSION: The
      risk for PTE is clearly determined by those variables which correlate with the
      severity, the extent of tissue loss and the penetrating nature of the brain
      trauma.

PMID- 9188899
TI  - Occurrence of only myoclonic jerks in juvenile myoclonic epilepsy.
AB  - OBJECTIVES: The clinical data on individuals who were diagnosed to have juvenile
      myoclonic epilepsy (JME) on the basis of myoclonic jerks alone has been analysed.
      The points in favour and against individuals with only myoclonic jerks being
      classified as "affected" for research on JME are discussed. MATERIALS AND
      METHODS: We studied 15 persons diagnosed with JME on the basis of only myoclonic
      jerks in a series of 161 patients with JME and their relatives. Detailed
      information on the seizure types in JME patients and their family members was
      collected. All affected individuals were examined by one person and had at least
      one conventional scalp EEG. CT/MRI of the brain was done as and when indicated.
      RESULTS: Nine of these were probands while 6 were the relatives of JME patients.
      The EEG was abnormal in 8 of 9 probands and 1 of 6 relatives with only myoclonic
      jerks. All the 9 probands and 2 relatives with only myoclonic jerks were treated
      with anti-epileptic drugs. Three of the 4 relatives had spontaneous remission of
      jerks after variable intervals. Four of 15 persons with only myoclonic jerks had
      a first degree relative with definite JME. CONCLUSIONS: It appears that persons
      with myoclonic jerks alone may represent a benign subgroup of JME that may be
      genetically distinct from classic JME and the jerks may even spontaneously remit
      in a few cases. It is suggested that those persons with only myoclonic jerks and
      a first degree relationship with a definite diagnosis of JME can be classified as
      "affected" for inclusion into molecular studies, till molecular tools are
      available to settle the issue of phenotypic variations in hereditary neurological
      disorders like JME.

PMID- 9188900
TI  - Economic consequences of multiple sclerosis for Canadians.
AB  - OBJECTIVES: To estimate the total costs of multiple sclerosis (MS) for all
      Canadians in 1994. METHODS: Prevalence-based study estimating disease-related
      societal costs for Canadians with MS in 1994. The human capital approach was used
      to estimate the value of lost productivity due to illness. Two components were
      revealed: first, direct costs, in terms of expenditures on hospital care, other
      institutions, physician services, other health professionals, drugs, and other
      expenditures; and second, indirect costs, in terms of lost productivity due to
      premature mortality and disability. RESULTS: The total costs of MS for Canadians
      were $502.3 million in 1994, with direct and indirect cost components at $188.6
      million and $313.7 million, respectively. CONCLUSIONS: This study highlights the
      scope and magnitude of the economic consequences of MS for Canadians. The costs
      calculated may be used to provide guidance in the setting of national priorities
      for research and prevention activities.

PMID- 9188901
TI  - Soluble CD8 and ICAM-1 in serum and CSF of MS patients treated with 6
      methylprednisolone.
AB  - OBJECTIVE: We studied the effects of large doses of 6-methylprednisolone (6-MP)
      on serum and cerebrospinal fluid (CSF) soluble CD8 (sCD8) and intercellular
      adhesion molecule-1 (sICAM-1) levels in clinically active multiple sclerosis (MS)
      patients. MATERIAL AND METHODS: Paired serum and CSF samples were from 16
      patients with definite MS, treated with 6-MP (1 g daily for 6 d) during an active
      phase of the disease. sCD8 and sICAM-1 levels were determined with ELISA before
      and after the therapy. RESULTS: Before 6-MP treatment, sCD8 levels in CSF were
      higher in MS patients than in patients with noninflammatory neurological disease
      and in healthy controls; sICAM-1 levels in serum and in CSF were higher in MS
      patients than in the two control groups. Ten of the 16 patients showed clinical
      improvement at the end of the treatment. After the therapy, serum and CSF sCD8
      levels increased, whereas serum and CSF sICAM-1 levels decreased. There was no
      correlation between clinical improvement and laboratory parameters. We evaluated
      sCD8 and sICAM-1 in serum samples from 10 patients 6 months after the 6-MP
      treatment, when the disease was clinically silent. Neither sCD8 nor sICAM-1
      levels differed from those of the control groups. CONCLUSIONS: Our results
      suggest that high doses of 6-MP can influence serum and CSF sCD8 and sICAM-1
      levels in active MS. At least part of the efficacy of corticosteroid treatment in
      MS might be ascribed to its effect both on the suppressive circuits of immune
      response, and on the expression of an adhesion molecule that favours lymphocyte
      trafficking across the blood-brain barrier.

PMID- 9188902
TI  - Absence of seven human herpesviruses, including HHV-6, by polymerase chain
      reaction in CSF and blood from patients with multiple sclerosis and optic
      neuritis.
AB  - Several members of the herpesvirus family have been implicated in the
      pathogenesis of multiple sclerosis (MS). Recently, HHV-6 viral antigen has been
      demonstrated in association to MS plaques, as well as DNA from human herpesvirus
      6 (HHV-6) in cerebrospinal fluid from a few MS patients by polymerase chain
      reaction (PCR). In the present study, CSF from patients with MS, optic neuritis
      and other neurological diseases, as well as consecutive CSF and serum samples
      from MS patients included in a clinical trial with acyclovir, were analysed by
      nested PCR for the presence of DNA from herpes simplex virus 1 and 2, Epstein
      Barr virus, varicella zoster virus, cytomegalovirus, human herpesvirus 6 and 7.
      No virus DNA was found in any CSF (n = 115) or serum (n = 116) sample. These
      findings argue against a continuous disseminated herpesvirus infection in MS, but
      do not rule out a lesion-associated, low-grade herpesvirus infection within the
      MS brain.

PMID- 9188903
TI  - Absence of entero- and cardioviral RNA in multiple sclerosis brain tissue.
AB  - OBJECTIVES: Epidemiological evidence suggests that an infectious agent may be
      involved in the pathogenesis of multiple sclerosis (MS). Picornaviruses are
      possible candidates for an etiological agent, because of their neurotropic
      properties and ability to cause chronic infections. MATERIALS AND METHODS:
      Autopsy brain tissue from 25 patients with clinically definite MS and 33 control
      patients without inflammatory neurological disease was tested with reverse
      transcription PCR specific for enteroviruses and cardioviruses. RESULTS: All
      specimens were found negative. CONCLUSION: These results do not support the
      theory of a persisting entero- or cardioviral infection as the cause of Ms as we
      found no evidence of the presence of entero- or cardioviral genomes in the brains
      from MS patients.

PMID- 9188904
TI  - Striatal dopaminergic loss without parkinsonism in a case of corticobasal
      degeneration.
AB  - Neurochemical analyses of post-mortem brain from cases of corticobasal
      degeneration are extremely rare although nearly 100 cases have been reported in
      the literature. We detail findings of neurotransmitter derangement in the basal
      ganglia of a case of neuropathologically confirmed corticobasal degeneration, who
      presented with dementia. The implications of severe neuronal loss in the
      substantia nigra and extremely low levels of dopamine and its metabolites in the
      striatum are considered in relation to the absence of an intrinsic extrapyramidal
      syndrome.

PMID- 9188905
TI  - Autonomic dysfunction in Parkinson's disease assessed by sympathetic skin
      response: a prospective clinical and neurophysiological trial on 50 patients.
AB  - To verify possible dysfunction of sympathetic skin activity in Parkinson's
      disease (PD), we studied the electrically evoked sympathetic skin responses (SSR)
      bilaterally at hands and feet in a group of 50 PD patients and in normal
      subjects. SSR was present in all patients. Nevertheless, significant differences
      in the latency and amplitude values were noted. In the group of patients
      prolongation of latency as well as the reduction of SSR amplitude correlates with
      age. The longer the disease the more SSR abnormalities could be found. Gender,
      type of clinical manifestation of PD or medication had no statistically
      significant effects. However, motor symptom asymmetries evaluated separately for
      each body side correlated well with interside asymmetries of SSR.

PMID- 9188906
TI  - The long-term prognosis of Guillain-Barre syndrome. Evaluation of prognostic
      factors including plasma exchange.
AB  - Fifty-two patients with Guillain-Barre syndrome (GBS) were re-examined 1-14 years
      (median 7 years) after the initial onset of symptoms. At the follow-up 38
      patients (73%) reported being completely symptom-free. Neurological examination
      revealed that 11 patients (21%) had motor and 16 patients (31%) had sensory
      signs, mainly distal in the lower limbs. One patient (2%) had cranial nerve
      signs. Fifteen patients (29%) had areflexia, generally of the ankle jerks. Severe
      pareses (high maximal disability grade), long duration of maximal symptoms and
      recovery were significantly associated with persistent disability. Age, sex,
      preceding infection, latency between infection and the onset of disease, weakness
      as an initial symptom, autonomic dysfunction, speed of progression, electro
      physiological signs of axonal degeneration, cerebrospinal-fluid protein
      concentration and treatment with plasma exchange did not significantly influence
      the disability grade at follow-up.

PMID- 9188907
TI  - Incidence of transient global amnesia in the Belluno province, Italy: 1985
      through 1995. Results of a community-based study.
AB  - INTRODUCTION: We sought to determine the incidence rate of all the new cases of
      first-ever-in-a-lifetime transient global amnesia in the Belluno province, Italy.
      Only two prospective epidemiological studies on TGA incidence have been performed
      to date, non in Italy. Our study aimed to provide reliable and comparable
      information on TGA incidence. MATERIAL AND METHODS: We undertook a prospective
      population-based study in the territory of the province of Bulluno, Italy,
      between June 1, 1992 and December 31, 1995. We also retrospectively reviewed the
      clinical records of all the patients with a diagnosis of amnesia seen in the
      hospitals of the study area from January 1, 1985 through May 31, 1992. RESULTS:
      During the prospective study period we identified 77 patients who experienced a
      first-ever TGA. The crude annual incidence rate was 10.4/100,000 (9.35/100,000
      for men and 11.37/100,000 for women). After adjustment to the European
      population, the incidence rate decreased to 8.60/100,000 per year. The crude
      annual incidence rate during the retrospective study period was 5.81/100,000. The
      demographic and clinical features of the two groups did not differ one to the
      other. CONCLUSIONS: The incidence rate of first-ever TGA registered in the
      province of Belluno, Italy, was closely similar to that reported in Turku,
      Finland and confirms that TGA is more common than has been usually proposed. We
      emphasize the usefulness of prospective, rather than retrospective,
      epidemiological studies for research on TGA.

PMID- 9188909
TI  - HIV dementia and apolipoprotein E.
AB  - The effect of apolipoprotein E genotypes on the occurrence of HIV dementia and
      HIV encephalitis was studied in a sample of 132 AIDS patients in whom clinical
      data on dementia was available and full autopsy had been performed. There was no
      statistically significant correlation between risk of HIV dementia or HIV
      encephalitis in relation to apolipoprotein E genotypes, even after correction for
      length of survival with AIDS and antiretroviral treatment.

PMID- 9188908
TI  - Cerebrospinal fluid proteins in subclinical and overt hypothyroidism.
AB  - PATIENTS AND METHODS: We analysed cerebrospinal fluid (CSF) albumin and
      immunoglobulin G (IgG) concentrations and psychometric performance in subclinical
      (n = 6) and overt hypothyroidism (n = 9) before and after 6 months with L
      thyroxine. RESULTS: In overt hypothyroidism, CSF albumin and IgG concentrations
      were increased before therapy [mean(SD): 328(156) mg/l and 69(27) mg/l], but
      within the reference interval [198(48) mg/l and 39(11) mg/l], P < 0.05, after
      therapy. In contrast, in subclinical hypothyroidism CSF protein concentrations
      were within the reference intervals before and after therapy. Psychometric
      testing indicated an improvement in performance in both groups. CONCLUSION: The
      increase in CSF proteins in overt hypothyroidism does not appear to be related to
      thyroid autoimmune disease per se, since we found no increase in CSF proteins in
      individuals with subclinical hypothyroidism and presence of thyroid antibodies.
      The increase might rather be caused by a blood-brain barrier dysfunction related
      to low thyroid hormone concentrations.

PMID- 9188910
TI  - Acute brachial plexus neuropathy as a presenting sign of peripheral nervous
      system involvement in paraproteinaemia.

PMID- 9188911
TI  - Effect of continued electroacupuncture on induction of interleukin-2 production
      of spleen lymphocytes from the injured rats.
AB  - The present study was to investigate the dynamic changes of the induction of
      interleukin-2 (IL-2) production of spleen lymphocytes from the rats after
      operative trauma stress and the regulatory effect of continued electroacupuncture
      (EA) stimulation of "Zusanli" (St. 36) and "Lanwei" (Extra 33) points on the
      induction of IL-3 production of spleen lymphocytes from the injured rats. The
      results showed that the induction of IL-2 production of the rat spleen
      lymphocytes was significantly decreased on day 1, 3, 5, 7 (P < 0.05), and the
      minimum level was on day 3 after operative trauma at both dilution 1:8 and
      dilution 1:16. The induction of IL-2 production was reserved to nearly normal on
      day 10. Continued stimulation by EA on "St. 36" and "Extra 33" points on day 3,
      5, 7 increased the induction of IL-2 production in various degrees at the two
      dilutions (P < 0.01), or P < 0.05). The results mentioned above implied that the
      immune function could be depressed by trauma stress. Continued EA stimulation
      could improve the immunosuppression induced by trauma stress.

PMID- 9188912
TI  - Acupuncture needles and the Seebeck effect: do temperature gradients produce
      electrostimulation?
AB  - Acupuncture may act through modifying bioelectric events and this may occur
      through different mechanisms including the application of external currents.
      According to the Seebeck effect which produces a potential difference when a
      temperature gradient is placed across a conductor, the physical properties of
      acupuncture needles may produce internal currents due to the temperature gradient
      across the needle when placed insitu. Such currents were detected when needles
      were differentially heated and these currents were found to be in the range
      capable of producing biological effects. The traditional design of acupuncture
      needles and traditional needle manipulations seem to maintain a temperature
      gradient across the needle and thus enhance the Seebeck effect.

PMID- 9188913
TI  - Impression on observing psychic surgery and healing in Brazil which appear to
      incorporate (+) qi gong energy & the use of acupuncture points.
AB  - In December, 1995, the author had the opportunity to observe an elderly psychic
      healer of East European origin in Sao Paulo, Brazil. This man specialized in
      cancer treatment by pointing with the fingers of his right hand at his patients,
      without actually touching them, spending an average of 30 to 40 minutes with each
      one. The author considered this to be Qi Gong treatment. In March, 1997 the
      author also observed 2 leading psychic healers in Brazil. One of them, named
      Rubens Farias, Jr. is a 43 year-old former engineer and computer programmer if
      European descent, who is commonly known as "Dr. Fritz III" because he is believed
      to be the spirit of Dr. Adolf Fritz, a German physician who died during World War
      I, operates through him. The other is "Dr." Hirota, a 53 year old former farmer
      of Japanese decent who lives near Campinas. About 120 kilometers outside of Sao
      Paulo and treats large numbers of people daily using indirect and/or hand-on
      healing techniques. On March 6, 1997, when the author visited "Dr. Fritz III"'s
      clinic in Sao Paulo with a group of Brazilian physicians, he was informed the
      about 1,400 patients had come that day. "Dr Fritz III" examined and treated the
      majority of the patients in less than one minute each, often asking very quick
      questions and then immediately beginning treatment. Most patients received
      injections of a dark-brown solution, which, some of the visiting doctors
      speculated, may be an iodine solution mixed with either alcohol or a local
      anesthetic. In many patients, he injected this solution near the pathological
      area or at an acupuncture point near the pathological area. When the needle of
      the syringe was in the acupuncture pint, he twirled it with his fingers several
      times and the withdrew it. Minor surgery was performed in about 1/5th of the
      patients with whom the author observed. Most of the surgical incisions were made
      on the midline of the tissue over the spine near the pathological area. The
      clamping of the blood vessels and the closings of the surgical wounds were
      performed by licensed surgeons or licensed nurses. Major surgery were done by
      "Dr. Fritz III" who used a rather primitive and unorthodox cutting technique.
      Except for major surgery, assistance was performed by volunteer nurses, including
      his wife. After the surgical wounds were closed, gauze band-aids were applied.
      When the surface of the gauze facing the wound was examined, it showed strong (+)
      Qi Gong energy according to the Bi-Digital O-Ring Test. Essentially, "Dr. Fritz
      III"'s treatment consists of acupuncture, injection of iodine with other
      substances near the pathological area, and (+) Qi Gong energy stored gauze which
      is applied to the acupuncture point, pathological area, or the site of surgery.
      "Dr." Hirota is another famous psychic healer whom the author was able to meet
      and observe in practice while in Brazil. "Dr." Hirota has been practicing for
      over 20 years. He usually sees patients who come to his clinic in the mornings
      and he claims to treat 1,000 to 2,000 patients daily between 9 AM and 12 noon.
      His main treatment also appears to be the application of external Qi Gong energy
      through the fingers of his right-hand, in combination with Shiatsu Massage and a
      manual procedure resembling chiropractic manipulation.

PMID- 9188914
TI  - Domestic mites from an acarologic perspective.
AB  - Knowledge of the taxonomic, physiologic, biologic, and ecologic characteristics
      of allergenic domestic mites contributes to the understanding of the causation of
      many cases of allergic asthma, and to the measures to be taken to control
      excessive mite occurrence in homes. Domestic mites, i.e., the combined group of
      storage mites living in the home environment and of pyroglyphid house-dust mites,
      belong to the subclass of the acari. This comprises also many other mites of
      medical and economic importance, together with thousands of free-living mites.
      Because of some species-specific properties of their allergenic products, it is
      important that the producing mite is always correctly identified. In spite of
      their small size (approx. 0.5 mm), domestic mites have well-developed and
      elaborate systems of respiration, digestion, and water balance, enabling them to
      live and survive in the various habitats of the home environment. Knowledge of
      the effects of the various and changing ecologic conditions in the home
      environment is helpful in developing strategies to prevent the establishment and
      growth of large populations of allergenic domestic mites.

PMID- 9188915
TI  - Prevention and nonpharmacologic treatment of mite allergy.

PMID- 9188916
TI  - Recombinant mite allergens. New technologies for the management of patients with
      asthma.
AB  - The introduction of molecular cloning techniques has led to advances in allergen
      identification and sequencing, production of recombinant allergens,
      identification of B-cell and T-cell epitopes, and tertiary structural analysis of
      allergen molecules. Over 10 groups of mite allergens have been cloned from
      Dermatophagoides spp., as well as several homologous allergens from Euroglyphus
      maynei, Lepidoglyphus destructor, and Blomia tropicalis. The availability of
      these allergens has made it feasible to consider their use for both diagnostic
      and therapeutic purposes. Several recombinant Dermatophagoides allergens show
      comparable reactivity on skin testing and in serologic assays to natural
      allergens, and cocktails of the recombinant proteins could be used as diagnostic
      reagents. New technologies have been developed for detection of allergen-specific
      IgE and for environmental allergen detection using rapid diagnostic tests. Novel
      approaches to immunotherapy are also being investigated, including T-cell-peptide
      based vaccines, allergen variants which lack IgE reactivity, and naked DNA
      vaccines. The application of allergen biotechnology should lead to improvements
      in the management of mite-allergic patients with asthma and represents a logical
      step toward reducing asthma mortality and morbidity.

PMID- 9188917
TI  - Measurement of mite allergen in the environment.

PMID- 9188918
TI  - Mite species of allergologic importance in Europe.

PMID- 9188919
TI  - Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year
      survey.
AB  - Studies on the epidemiology of common adverse cutaneous drug reactions have
      rarely been reported, since they can only be successfully conducted in clinics of
      internal medicine employing consultant dermatologists and having a comprehensive
      or intensive system of monitoring. Between 1974 and 1993, the adverse skin
      reactions occurring in divisions of general internal medicine of three different
      hospitals were monitored by a computerized comprehensive system. The "drug
      monitoring patient" was defined as the recipient of at least one drug during
      hospitalization. The relationship of the skin reactions to drug causality in
      these patients had to be either definite (proven by re-exposure) or probable
      (drug relation greater than that of nondrug causality). The skin reactions were
      classified into four diagnostic groups. Maculopapular exanthema, urticaria, and
      vasculitis were the three main groups. The fourth group comprised cases of
      nonhomogeneous but clinically well-defined special exanthema. For selected drugs
      and years of observation, special emphasis was placed on the study of time
      patterns (reaction time, exposure time). A total of 1317 definite or probable
      drug-induced skin reactions occurred during the hospitalization of 48,005
      consecutively admitted "drug-monitoring patients": 1201 cases of maculopapular
      exanthema, 78 cases of urticaria, 18 cases of cutaneous vasculitis, and 20 cases
      of special exanthema (five of erythema multiforme minor, six of fixed eruption,
      one of photosensitivity reaction, and eight of acneiform eruption). The main
      drugs involved did not differ for the three main types of skin reactions,
      penicillins ranking in the first place, followed by sulfonamides--most often
      combined with trimethoprim--and in the third place nonsteroidal anti-inflammatory
      drugs. The reaction time (time from last drug exposure to first skin
      manifestation) for urticaria showed a relevant proportion of the acute type
      (within 1 h) and most of the subacute type (1-24 h). For maculopapular exanthema,
      the subacute or, rarely, the latent type (1-8 days, exceptionally more than 8
      days) predominated. For aminopenicillins, the rate of occurrence of skin
      reactions increased with increasing exposure time up to 12 days, and then
      markedly diminished. Possibly due to the tendency to withdraw suspected drugs
      even in the case of minor (e.g., maculopapular) skin reactions, no severe events
      such as erythema multiforme major/Stevens-Johnson syndrome or toxic epidermal
      necrolysis occurred.

PMID- 9188920
TI  - Anti-Candida albicans IgE and IgG subclasses in sera of patients with allergic
      bronchopulmonary aspergillosis (ABPA).
AB  - We performed immunoblotting experiments to determine specific IgE and IgG
      subclass responses to Candida albicans antigens in allergic bronchopulmonary
      aspergillosis (ABPA) patients. This is a first report describing C. albicans
      antigens recognized by serum IgE and IgG subclasses of ABPA patients sensitized
      to that yeast. Among the various antigens reacting with serum IgE, a 43-kDa
      component was recognized by all seven patients and can be considered a major
      antigen of C. albicans for this particular group of patients. By comparison, only
      20% of a group of asthmatic atopics (25 patients) and 10% of a group of normal
      controls (10 subjects) were 43-kDa positive. Multiple banding patterns, revealing
      no major antigen, were observed for all four IgG subclasses except for IgG1 in
      one case. In particular, the 43-kDa component was not always recognized by all
      the patients. Furthermore, oral or inhaled steroid treatment appears to have no
      impact on the specific IgE immunopatterns obtained. Using immunoelectron
      microscopy, we localized IgE-binding primarily in the mannoprotein-containing
      layers of the C. albicans cell wall. In conclusion, C. albicans-IgE and IgG
      subclasses may participate in the physiopathology of ABPA by exacerbating
      pulmonary infiltrates (IgE) and inducing eosinophil-mediated inflammatory
      reaction (IgG1, IgG3).

PMID- 9188921
TI  - "Latex-fruit syndrome": frequency of cross-reacting IgE antibodies.
AB  - An association between allergies to latex proteins and to various foods has been
      reported and confirmed by RAST and immunoblotting inhibition. However, no
      significant data had been collected on the frequency of specific IgE antibodies
      to fruits in these patients and the frequency of a history of fruit intolerance.
      Serum samples of 136 patients with well-documented, clinically relevant,
      immediate-type hypersensitivity against latex proteins were analyzed for IgE
      antibodies against a panel of different fruits. Patient history of food
      intolerance was documented by a standardized questionnaire. Fruit-specific IgE
      antibodies were detected in 69.1% of serum samples. Cross-reacting IgE antibodies
      recognizing latex and fruit allergens (papaya, avocado, banana, chestnut, passion
      fruit, fig, melon, mango, kiwi, pineapple, peach, and tomato) were demonstrated
      by RAST-inhibition tests. Of our patients, 42.5% reported allergic symptoms after
      ingestion of these fruits and a total of 112 intolerance reactions were recorded.
      However, fruit-specific IgE antibodies were detected only in serum samples from
      32.1% of the patients who perceived symptoms due to these fruits. Thus, serologic
      tests seem to be of low significance for prediction o food allergy in latex
      allergic patients.

PMID- 9188922
TI  - Analysis of cross-reactive allergens from American and German cockroaches by
      human IgE.
AB  - Serum from atopics hypersensitive to the American cockroach were examined for
      their specific IgE to American and German cockroaches by the fluoroallergosorbent
      test (FAST). Of 44 sera tested, 86.4% (38/44) contained IgE to American and
      German cockroaches, and 13.6% (6/44) were found to be positive for American
      cockroach alone by FAST. Nine individual sera containing IgE antibodies to both
      cockroaches were used to analyze the cross-reacting allergens in the crude
      American and German cockroach extracts by FAST inhibition and immunoblotting FAST
      inhibition studies showed various degrees but similar inhibition of binding of
      human IgE to solid-phase American cockroach extract. Proteins from both cockroach
      extracts were separated on SDS-PAGE followed by immunoblotting, and the results
      showed considerable heterogeneity in the IgE-binding patterns with each of the
      cockroach extracts for the same nine individual sera. Components with apparent
      molecular weights of 60, 52, 49, 38, and 12 kDa from both the American and German
      cockroaches were able to bind IgE antibody. These results suggest the presence of
      cross-reactive allergens in the American and the German cockroaches.

PMID- 9188923
TI  - Serum eosinophil peroxidase (EPO) levels in asthmatic patients.
AB  - Eosinophil granular proteins are a useful eosinophilic activation marker in
      asthmatic patients. In this study, the eosinophil peroxidase (EPO) levels were
      assessed in different stages of bronchial asthma, in 123 patients suffering from
      asthma, classified as mild (n =49), moderate (n = 49), and severe (n = 25),
      according to the International Consensus Report of Diagnosis and Treatment of
      Asthma, as well as in 27 healthy controls, with the aim of evaluating the
      importance of this protein as a severity marker in bronchial asthma, and its
      possible correlation with parameters such as anamnesis, respiratory function
      tests, and peripheral blood eosinophil count, and also with some allergologic
      diagnostic tests, both in vivo and in vitro. The geometric mean serum level of
      EPO was 9.3 +/- 11.3 ng/ml (median +/- SD) in controls, 28 +/- 37.8 ng/ml in the
      asthmatic patients. Depending on the asthma severity, the EPO levels were 25 +/-
      30.5; 29 +/- 37.1, and 41 +/- 47.3 ng/ml in mild, moderate, and severe
      asthmatics, respectively, being the significant differences between the group of
      patients with mild and severe asthma (P < 0.001). The number of eosinophils (eos)
      in peripheral blood was 157 +/- 20 eos/mm3 in the controls, 334/35 eos/mm3 in
      mild asthmatics, 510 +/- 87 eos/mm3 in moderate asthmatics, and 658 +/- 72
      eos/mm3 in severe asthmatics, with significant differences between all groups
      (from P < 0.05 to P < 0.001). Both the serum levels of EPO and the number of
      eosinophils were greater in patients with active asthma patients with inactive
      asthma (P < 0.001). Significant negative correlations (P < 0.001) were found
      between serum levels of EPO and FEV1 (rs = 0.30), MEF25-75 (rs = -0.33) and MEF50
      (rs = -0.34), and a good positive correlation (rs = 0.80, P < 0.001) was found
      between EPO levels and the number of eosinophils in peripheral blood. We also
      found a significant positive correlation between eosinophil number and clinical
      score (rs = 0.54, P < 0.001) and between EPO levels and the mentioned score (rs =
      0.46, P < 0.001).

PMID- 9188925
TI  - Oral allergy syndrome to a jackfruit (Artocarpus integrifolia).
AB  - A 30-year-old man from the Philippines with pollen allergy noted the appearance
      of oral allergy syndrome (OAS) after eating raw apple, raw peach, raw celery, and
      recently, jackfruit (Artocarpus integrifolia), a tropical fruit which belongs to
      the Moraceae family (mulberry) and to the genus Artocarpus (breadfruit tree).
      Despite the patient's multiple sensitization in skin prick tests and in the
      Pharmacia CAP System to birch, grass, mugwort pollen, related fruits and
      vegetables, and jackfruit, in RAST-inhibition studies neither rBet v 1 nor rBet v
      2 (profilin), the well-known cross-reacting allergenic components in OAS, could
      inhibit the specific IgE response to jackfruit. Whether the reaction to jackfruit
      is specific or whether other pollen-related, cross-reacting allergenic components
      exist should be investigated further.

PMID- 9188924
TI  - Anti-inflammatory drugs do not alleviate bronchial hyperreactivity in Sjogren's
      syndrome.
AB  - Bronchial hyperreactivity (BHR) is found in Sjogren's syndrome, as in a number of
      other conditions such as asthma. BHR associated with asthma can be effectively
      treated with corticosteroids or sodium cromoglycate. We treated 19 Sjogren's
      syndrome patients with BHR with inhaled budesonide and inhaled cromoglycate for 6
      weeks each. None of the treatment had any significant effect on symptoms of
      hyperreactivity or lung function. There was no effect on BHR measured as
      methacholine reactivity. Primary Sjogren's syndrome is a disease with
      inflammation not only in the salivary and lacrimal glands but also in the
      pulmonary alveoli and the bronchi. The main inflammatory cell is the lymphocyte,
      whereas, in the bronchi in asthma, the eosinophil granulocyte is the
      characteristic inflammatory cell. The cause of the discrepancy with regard to
      treatability of BHR in asthma and in Sjogren's syndrome is not known. Possibly
      not all BHR is caused by inflammation. There is not a perfect correlation between
      inflammation and hyperreactivity even in asthma. Even in the bronchial
      inflammation and the asthma symptoms are easy to treat with anti-inflammatory
      medicines, a considerable component of BHR usually still remains, as measured
      with methacholine or histamine.

PMID- 9188926
TI  - Angiotensin-converting enzyme inhibitor-induced angioedema: late onset, irregular
      course, and potential role of triggers.
AB  - Angioedema is a rare but potentially life-threatening adverse effect of
      angiotensin-converting enzyme inhibitors (ACEI) which usually occurs within the
      first weeks of therapy. We report three patients in whom ACEI-induced angioedema
      began with a late onset of 12-33 months, and who had an irregular, unpredictable
      course under ACEI therapy. In two patients, other drugs or trauma appeared to
      trigger some of the episodes. After withdrawal of the ACEI, the trigger drugs
      were well tolerated in provocation tests and upon re-exposure. To avoid putting
      some patients unnecessarily at risk for long periods, one should consider this
      irregular pattern of ACEI-induced angioedema and regularly monitor patients for
      this adverse effect.

PMID- 9188927
TI  - Demonstration of the high-affinity IgE receptor (Fc epsilon RI) on Langerhans'
      cells of diseased nasal mucosa.
AB  - Langerhans' cells in the skin have recently been shown to bind IgE molecules via
      the high-affinity IgE receptor (Fc epsilon RI). Using two highly specific
      antibodies against the antibody-binding alpha-chain of this receptor, 29C6 and
      6F7, we demonstrate by immunohistochemistry and immunoelectron microscopy that
      Langerhans' cells of diseased nasal mucosa can express the Fc epsilon RI. Tissue
      sections from hyperplastic nasal conchae and nasal polyps of atopic and nonatopic
      patients have shown no basic differences in epithelial Fc epsilon RI-bearing
      cells. Only a few cells expressed the low-affinity IgE receptor (Fc epsilon RII)
      (Tu1 antibody) in some sections. These findings suggest that Langerhans' cells
      play an important role in the induction of transepithelial IgE-mediated allergy
      and in the mediation of inflammation of the nasal mucosa via their Fc epsilon RI.

PMID- 9188928
TI  - Can an antihistamine delay appearance of hay fever symptoms when given prior to
      pollen season?
AB  - Mizolastine is a new, nonsedating antihistamine providing satisfactory symptom
      relief in allergic conditions. The purpose of this study was to determine whether
      the onset of hay fever symptoms could be delayed in patients known to suffer
      seasonal allergic rhinoconjunctivitis symptoms if mizolastine was given before
      the pollen season. This double-blind study involved 342 patients, randomly
      allocated to once-daily 10 mg mizolastine (n = 115), once-daily 120 mg
      terfenadine (n = 116), or placebo (n = 111) groups. All patients started
      treatment on 1 May, before the onset of the grass pollen season. The prophylactic
      effect of test drugs was assessed on their ability to delay the time to the first
      hay fever crisis of the season, which was defined by the occurrence of one of the
      following events: use of rescue medication, study withdrawal because of treatment
      failure, or total diary symptom score over 18. Active treatments prolonged the
      time to the first crisis by approximately 1 week (mizolastine 55 days,
      terfenadine 57 days) in comparison with placebo (50 days) (survival curve
      analysis: Logrank test, P = 0.01; Wilcoxon test, P = 0.03). Tolerability was
      satisfactory and comparable between groups. Thus, mizolastine can be safely used
      to delay and to treat symptoms of seasonal allergic rhinitis.

PMID- 9188929
TI  - Fluticasone propionate aqueous nasal spray compared with oral loratadine in
      patients with seasonal allergic rhinitis.
AB  - The effectiveness and safety of fluticasone propionate aqueous nasal spray (200
      micrograms once daily for 4 weeks) were compared with those of loratadine (10 mg
      once daily for 4 weeks) in 114 adults and adolescents with seasonal allergic
      rhinitis in this multicenter, double-blind, double-dummy, randomized, parallel
      group study. Patients recorded their nasal symptoms (nighttime and daytime
      obstruction, sneezing, itching, rhinorrhea, and overall discomfort) using a 4
      point scale (0 = no symptoms, 3 = very frequent symptoms) in daily diaries.
      Clinicians assessed patients' nasal symptoms (nighttime and daytime obstruction,
      sneezing, itching, and rhinorrhea) using a 4-point scale at every scheduled
      visit. Clinicians and patients assessed the overall effectiveness of treatment at
      the end of the study. Fluticasone propionate improved clinician-rated total nasal
      symptom scores (defined as the sum of five nasal symptoms) more than loratadine
      at the 2-week and 4-week assessments (P < or = 0.008). Clinicians give
      fluticasone propionate better global ratings than loratadine (P = 0.04). After 4
      weeks of treatment, between-group differences in clinician-rated individual nasal
      symptoms favored fluticasone propionate (P < 0.05), with the exception of nasal
      itching (P = 0.11). These findings were confirmed by between-group differences in
      the percentages of symptom-free days calculated from patient-recorded daily diary
      card data. Both treatments were well tolerated. The incidence of adverse events
      between groups was similar. Fluticasone propionate aqueous nasal spray 200
      micrograms administered once daily in the morning was more effective than
      loratadine 10 mg administered once daily for the treatment of seasonal allergic
      rhinitis.

PMID- 9188930
TI  - Efficacy of mequitazine in comparison with placebo assessed by ocular challenge
      with allergen in allergic conjunctivitis.
AB  - Pharmacologic intervention in the management of allergic conjunctivitis was
      evaluated with different topical ocular agents in man. Their effect can be
      precisely assessed with the conjunctival provocation test (CPT). A potent
      specific H1-receptor antagonist, 0.05% mequitazine eye-drops, was tested in a
      double-blind randomized, placebo-controlled study using CPT with grass pollen
      allergens. Twenty healthy subjects allergic to grass pollen were included outside
      the pollen season after a positive CPT screening. They received one drop of 0.05%
      mequitazine in one eye and the vehicle in the contralateral eye in a random
      order, four times daily for 5 days. CPT was performed 15 min after the last
      instillation, and the threshold dose inducing a positive reaction was determined.
      Results were given by Abelson's composite score including redness, chemosis,
      tearing, and itching. Topical 0.05% mequitazine significantly reduced the
      composite score compared to placebo. The allergen threshold concentration which
      induced the positive conjunctival reaction was higher in mequitazine pretreated
      eyes. No side-effect was reported. These data clearly suggest that mequitazine
      has potential to treat allergic conjunctivitis.

PMID- 9188931
TI  - Comparison of concentrations of Cry j 1 and Cry j 2 in diploid and triploid
      Japanese cedar (Cryptomeria japonica) pollen extracts.
AB  - Japanese cedar (Cryptomeria japonica) possibilities has been a serious allergic
      disease in Japan. There are two kinds of Japanese cedar trees; the popular one is
      diploid, the less popular is triploid. These trees are not very different
      morphologically. However, the relative allergenicity of their pollens is unknown,
      although both major allergens, Cry j 1 and Cry j 22, have been purified and
      cloned from the diploid line. Triploid trees are sterile and the allergenicity of
      their pollen may differ. Using Japanese-cedar-allergic patient sera, we compared
      the concentration of these two major allergens in both kinds of pollen. Pollen
      collected from different years and regions was also studied. The results indicate
      that triploid tree pollen extract has lower concentrations of both major
      allergens; therefore, the pollen may be less allergenic.

PMID- 9188932
TI  - Cockroach allergen in house dust.
AB  - The cockroach allergen (Bla g 1) content was determined in the floor dust of 46
      homes with recent cockroach extermination in Amsterdam, The Netherlands. IgE
      antibodies to Blattella germanica, house-dust mite, cat dander, dog dander, and a
      mixture of molds were determined in venous blood samples of 46 children (4-12
      years) and one of their biologic parents (24-54 years). Specific IgE to cockroach
      was also determined in a sample of the general population studied in a previous
      case-control study, one group (n = 20) with three groups (n =76) without history
      of cockroach infestation of the home. Cockroach allergen was detected in floor
      dust from 44% of the homes, with levels up to 3899 ng Bla g 1/g. Seven of the 46
      adults and only one of the 46 children studied had positive RAST to cockroach.
      Geometric mean cockroach allergen concentrations in living room and master
      bedroom of sensitized adults were similar to those of nonsensitized adults. In
      the groups of children without a history of cockroach infestation of the home,
      positive RAST against cockroach was observed in 16% of the children with
      respiratory symptoms, in 4% of the children without respiratory symptoms, and in
      48% of the children with two or more positive RAST to other allergens. Of the 18
      children with positive RAST against cockroach, only one had a history of
      cockroach infestation of the home and 16 (89%) had also positive RAST against
      house-dust mite.

PMID- 9188933
TI  - Rapid expression of the CD69 antigen on T cells and natural killer cells upon
      antigenic stimulation of peripheral blood mononuclear cell suspensions.
AB  - The CD69 antigen has been identified as the earliest activation marker on the
      surface of cytokine- or mitogen-activated lymphocytes. The expression of this
      molecule may be a useful early marker of antigen- or allergen-specific activation
      of lymphocytes in vitro. We evaluated the expression of the CD69 and CD25
      antigens on antigen- or allergen-stimulated lymphocytes and the proliferative
      responses as detected by thymidine incorporation. Peripheral blood mononuclear
      cells (PBMC) of allergic patients sensitized to Dermatophagoides pteronyssinus,
      bovine casein, or nickel sulfate were cultured in the absence or presence of
      clinically relevant allergens, tetanus toxoid, or recombinant interleukin (IL)-2.
      The respective binding of CD69 or CD25 antibodies to PBMC and thymidine
      incorporation were measured. An early expression of CD69, but not of CD25,
      antigen was detectable after 24-72 h of stimulation on up to 80% of natural
      killer (NK) cells and up to 10% of CD4+ T cells in PBMC cultures. Anti-IL-2
      antibodies inhibited these increases of CD69 on NK cells and T cells by up to
      60%. After 6 days of antigenic stimulation, the rates of both CD25+ and CD69+
      lymphocytes were higher. Seventy-four percent of the CD25+ PBMC but only 55% of
      the CD69+ cells were CD3+ T lymphocytes at this time. No qualitative differences
      were detectable in allergen- or tetanus-toxoid-stimulated PBMC from allergic
      patients. The high expression of CD69 on NK cells in antigen-stimulated cultures
      suggests that these cells are easily activated by cytokines from antigen
      stimulated T cells. CD69+ NK cells may serve as early-indicator cells in cultures
      with antigen- or allergen-stimulated mononuclear cells.

PMID- 9188934
TI  - Urinary leukotriene E4 and 11-dehydrothromboxane B2 in patients with aspirin
      sensitive asthma.
AB  - The objective of this study was to define the participation of cysteinyl
      leukotrienes (LTs) or thromboxane A2 in the pathogenesis of aspirin-sensitive
      asthma (ASA). Leukotriene E4 (LTE4) and 11-dehydrothromboxane B2 (11DTXB2) values
      in spot urine were measured in 22 asthmatics with a history of aspirin
      sensitivity and in 17 without such a history (non-aspirin-sensitive asthma
      [NASA]) in the outpatient clinic. The urinary LTE4 value was significantly higher
      in ASA patients than in NASA (340 +/- 47 vs 65 +/- 15 pg/mg.cr, P < 0.001), but
      there was no significant difference in urinary 11DTXB2 between the two groups
      (891 +/- 77 vs 657 +/- 90 pg/mg.cr). A high value of LTE4 was not associated with
      type of asthma, severity of disease, oral prednisolone treatment, sex, or age. A
      higher value of 11DTXB2 was observed in the atopic type than the nonatopic type
      in ASA (1086 +/- 111 vs 697 +/- 147 pg/mg.cr, P < 0.05). No correlation was
      observed between urinary LTE4 and 11DTXB2 in either ASA or NASA. In conclusion,
      LTs may play an important role in the pathogenesis of ASA, and TXA2 in the
      pathogenesis of the atopic type in ASA.

PMID- 9188935
TI  - Meswak, a novel allergen.

PMID- 9188936
TI  - Anaphylaxis to saffron.

PMID- 9188937
TI  - Fixed drug eruption (FDE) caused by norfloxacin.

PMID- 9188938
TI  - Hypersensitivity pneumonitis induced by exposure to the legume algarroba.

PMID- 9188940
TI  - Nasal sensitization.
AB  - Because humans breathe through the nose, the nasal mucosa becomes sensitized to
      inhalant allergens. Allergic rhinitis is, together with allergic conjunctivitis,
      the best example of a type I hypersensitivity reaction. It is an inflammation of
      the nasal mucosa induced by specific immune recognition of exogenous allergens.
      The production of IgE plays a major role in the pathophysiology. During the
      sensitization phase, an antigen is presented to an antigen-presenting cell at the
      epithelial level. Cells that express class II major histocompatibility complex Ia
      on their surface can act as an antigen-presenting cell for immunocompetent cells
      (dentritic cells, monocytes, macrophages, B lymphocytes and epithelial cells).
      Macrophages and Langerhans cells are increased in number in the nasal mucosa of
      patients with seasonal allergic rhinitis during the season and also after
      allergen challenge. Topical corticosteroid treatment reduces the number of
      Langerhans cells in the epithelium. The epithelium also participates in antigen
      presentation through its possession of antigen-binding surface proteins. The
      antigen is finally presented to CD4 T-helper cells and B cells; this is monitored
      by cytokines and leads to the development of memory cells and IgE-producing
      plasmocytes. In humans, IL-4 has been shown to be capable of differentiating B
      cells into IgE-producing plasma cells. The IL-4 production is inhibited by
      interferon gamma and by prostaglandin E2. The CD4+ cells also produce IL-2, which
      causes differentiation and proliferation of T lymphocytes, and IL-3, IL-5, IL-6
      and IL-7, which stimulate the B lymphocytes. Topical administration of anti
      allergic drugs or immunotherapy seems to be a logical approach in the treatment
      of patients with allergic rhinitis, because it has very direct activity on the
      main components of nasal sensitization.

PMID- 9188941
TI  - Local nasal immunotherapy: experimental evidences and general considerations.
AB  - The possibility of local hyposensitization in allergies was envisaged since the
      first decades of the century and then sporadically employed, whereas controlled
      clinical trials of local nasal immunotherapy (LNIT) were performed only during
      the last 20 years. Studies currently available agree on the clinical efficacy of
      the treatment. LNIT was demonstrated capable of reducing symptoms both in pollen-
      and mite-induced rhinitis, and of modifying the specific target organ
      responsivity. Indeed, aqueous extracts appeared to be more effective than
      modified ones but were also charged by troublesome local side effects, while the
      recently introduced powdered extracts seemed to overcome this problem,
      maintaining a favourable clinical effectiveness. In a recent study we
      demonstrated a significant effect of LNIT on local allergic inflammation. LNIT
      reduced both the inflammatory infiltration and ICAM-1 expression on nasal
      epithelial cells upon specific nasal challenge. The effects on specific challenge
      appeared long-lasting, but the clinical efficacy seemed to depend strictly upon
      preseasonal treatment. LNIT with powdered extracts appears an effective, safe and
      well-tolerated treatment for allergic rhinitis. Nevertheless, its particular
      administration technique requires a careful choice of patients. Finally, a
      socioeconomical analysis shows a favourable cost/benefit ratio for LNIT if
      compared to classic subcutaneous immunotherapy.

PMID- 9188942
TI  - Pharmacokinetics of allergens after local administration.
AB  - The authors review the status of knowledge on absorption and kinetic of allergens
      administered on nasal mucosa. Intranasal administration is well known in
      pharmacology, and has been used for a long time for peptide drugs, mainly
      hormones. The immunological response to intranasally administered antigens have
      been studied in some experimental models: bovine Rnase, dextran, KLH, tetanus
      toxoid. These studies showed in atopic people a greater absorption of antigens by
      nasal mucosa compared to normal individuals, a difference that might be of
      importance in the pathogenesis of atopic diseases. The absorption rate of
      peptides through nasal mucosa has been studied biologically by PK-test with Rnase
      and peanut allergen, and a consistent passage of intact molecules has been
      observed. Using as tracer 125I-labelled human albumin, transport across the nasal
      mucosa has been demonstrated in 3/9 normal subjects, 1/9 patients with extrinsic
      asthma and 9/10 patients with atopic rhinitis. In experimental animals (rabbits)
      the passage of allergens through the nasal mucosa has been confirmed using 125I
      labelled Parietaria allergens that showed a peak in the bloodstream 60 min after
      administration. It is concluded that peptide molecules such as allergens can be
      absorbed through the nasal mucosa and reach the bloodstream, and that in atopic
      patients nasal permeability is enhanced.

PMID- 9188944
TI  - Rhinomanometry.
AB  - The importance of nasal obstruction is stressed as one of the cardinal symptoms
      in allergic rhinitis and the major symptom of the late phase reaction; therefore
      the objective measurement of this symptom is of the utmost importance. The
      international committee on objective assessment of the nasal airway advocated
      rhinomanometry as a reliable method for measuring this symptom. The author's
      experience with this method after nasal challenge during the early and late
      phase, in 18 patients and 10 normal volunteers, is discussed. If total nasal
      resistance is considered then 41% of the patients showed a late phase. When
      considering unilateral nasal resistance a late phase was observed in 82% of the
      patients.

PMID- 9188943
TI  - Monitoring methods for local nasal immunotherapy.
AB  - When a patient is affected by specific vasomotor rhinopathy (allergic rhinitis),
      both perennial and seasonal, all the nasal functions are altered to various
      degrees. For this reason, in the evaluation of the efficacy of an antiallergic
      therapy we include: 1) anterior rhinoscopy; 2) active anterior rhinomanometry; 3)
      positioned acoustic rhinometry; 4) determination of mucociliary transport time;
      and 5) specific nasal provocation test. Active anterior rhinomanometry performed
      according to the directions of the International Committee on Standardization
      allows reliable assessment of the nasal respiratory function. Acoustic rhinometry
      is an objective method to assess the geometry of nasal cavities but, as a new
      method, needs more standardization with particular care in connecting the nose
      piece to the nostril. Both these tests performed before and after local
      administration of nasal decongestants allow quantification of the congestion
      degree of the nasal mucosa. Determination of mucociliary transport time,
      according to the method of coloured tracer, is easy to perform and may be
      considered a reliable indicator of the mucosa eutrophism. In our clinical
      experience we have often found mucociliary transport times delayed or even
      blocked, especially in patients affected by perennial allergic rhinitis.
      According to our experience the specific nasal provocation test is one of the
      most important tests in this field: it is more sensitive than skin tests and RAST
      in the asymptomatic phase and it is able to show organ allergies. In this paper
      we review the importance of this test, the methodology we currently use as well
      as changes after local nasal immunotherapy.

PMID- 9188945
TI  - Rhinopharyngoscopy, computed tomography and magnetic resonance imaging.
AB  - Rhinitis is defined as nasal congestion, sneezing, itching and rhinorrhoea,
      recently classified as allergic, infective, structural or "other". The increasing
      employment of flexible rhynolaringoscopy may represent one of the most useful
      diagnostic tools in the complex differential diagnosis between allergic and
      nonallergic rhinitis. Furthermore, chronic allergic rhinitis, with secondary
      impairment of mucociliary clearance and the plethora of frequent anatomical
      variations, especially in the ostiomeatal complex, appear to predispose the
      patient to recurrent rhinosinusitis. In the last two decades, a better
      understanding of mucociliary clearance of nasal cavity and paranasal sinuses has
      shifted the attention from the maxillary sinuses to the area of the antherior
      ethmoid sinuses. Plain film radiographic examination, the historical standard,
      due to its inability to individualize ethmoid and sphenoid disease, is being
      rapidly supplanted by computed tomography and magnetic resonance imaging in the
      diagnosis of rhinosinusitis. In allergic and non-allergic rhinitis the diagnostic
      role of magnetic resonance imaging and computed tomography is still under debate.
      Computed tomography and magnetic resonance imaging are more efficient in
      demonstrating the bone wall, mucosal layer and sinus content than classical and
      computerized radiology; they have a higher diagnostic performance index in spite
      of a higher cost and, for computed tomography, a higher radiation dose.

PMID- 9188946
TI  - Specific nasal provocation test with powder allergen.
AB  - Reported here are the results of a large-scale trial conducted under the guidance
      of Prof. Giovanni Motta, which I coordinated. A total of 656 patients with nasal
      hyperreactivity were recruited in 51 Italian centres (18 in the north of Italy,
      20 in central Italy and 13 in the south). The trial's results were as follows. 1)
      A clear clinical prevalence of sensitization to different allergens in the
      different areas of Italy, which could be roughly classified thus: a) in Northern
      Italy birch and grasses were in the main species; b) in Central Italy mites
      prevailed but oleaceae were also significant; c) in Southern Italy parietaria and
      oleaceae were the prevailing species. 2) Most cases were sensitive to several
      allergens, although a considerable proportion (22%) actually presented reactions
      only to one allergen and those responding account of the patients sensitive to
      only one allergen and those responding to a main allergen, the proportion of
      patients reacting clinically to only one allergen rises to 64%. 4) The specific
      nasal provocation test (sNPT) offers specificity comparable to in vivo diagnostic
      methods such as the prick test, and in vitro methods such as RAST, but is much
      more sensitive. 5) The sNPT can be done in any season. 6) The sNPT is highly
      specific below a threshold value of nasal reactivity, which can be identified for
      each allergen studied and expressed in Allergenic Units. 7) In patients in whom
      the prick test shows multiple sensitivity, the specific NPT identifies the
      allergen presumably responsible for the nasal reactions (main allergen). In the
      light of these findings double-blind specific immunotherapy was started, to last
      1 year, in 107 patients (49 given placebo and 58 active treatment), with nasal
      allergy to grasses, parietaria and mites. The results of this treatment were as
      follows: 74.1% of patients presented a reduction in nasal resistance, measured by
      dynamic anterior rhinomanometry, indicating relief of nasal obstruction;
      mucociliary transport time became normal in 81% of patients, meaning that
      rhinorrhoea had become less marked; there was significant rise in the nasal
      reactivity threshold in 74.1% of patients, illustrating the degree of
      desensitization achieved; nasal IgA increased by 62.5% of patients and IgG in
      55.2% indicating improvement in the local immunological picture. No such
      improvements were detectable in the patients given placebo. In conclusion,
      therefore, the findings of this trial in allergic rhinitis underline that the
      specific NPT proved more sensitive than other in vivo and in vitro diagnostic
      methods and is unquestionably a fundamental investigational approach for
      assessing nasal allergies, identifying the allergens causing the symptoms and
      setting up rational local immunotherapy. The sNPT also showed the efficacy of
      specific intranasal immunotherapy.

PMID- 9188947
TI  - Clinical efficacy and safety of local nasal immunotherapy.
AB  - Local nasal immunotherapy represents an alternative route of allergen
      administration. It was proposed to overcome the risk of systemic reactions rarely
      reported during the traditional subcutaneous immunotherapy. Some studies carried
      out in the past generally showed good efficacy but poor tolerability. The aqueous
      extracts mostly used in these studies carry some drawbacks such as the volume
      effect, self-digestion and the difficulty of administering reproducible dosages.
      The recent availability of allergen extracts in powder form has led to better
      stability and standardization. The studies carried out with these freeze-dried
      allergens showed clinical efficacy and good tolerability in perennial (mite, cat)
      and seasonal (grass, birch, Parietaria) allergic rhinitis. According to these
      findings this new local nasal immunotherapy with extract in powder form
      represents a suitable alternative to the traditional immunotherapy in the
      treatment of allergic rhinitis.

PMID- 9188949
TI  - Milestones in the biology and pharmacology of H1-receptor antagonists.
AB  - Daniele Bovet's pioneering discovery that a series of compounds possessing anti
      histamine activity reduced the symptoms of anaphylaxis provided the proof that
      histamine plays a pivotal role as a mediator of allergic reactions. Basophils and
      mast cells are the major sources of histamine in man and they are thus one of the
      primary effector cells of allergic inflammation. Some H1-receptor antagonists
      possess a variety of antiinflammatory activity to H1 antagonism in vitro and in
      vivo. This promising area should be explored further and much remains to be done
      in the evaluation of the immunomodulatory effects of anti-histamines.

PMID- 9188948
TI  - Nasal immunotherapy in pollen-sensitive children.
AB  - Subcutaneous specific immunotherapy has a considerable risk of side effects,
      including severe life-threatening ones or even death. The disadvantages and
      problems of this kind of therapy gave rise to looking for new ways of
      hyposensitization. In allergic rhinitis the local (nasal) immunotherapy may be
      effective. We studied the efficacy of local nasal immunotherapy (Allerkin) in
      grass and ragweed allergic children suffering from seasonal atopic rhinitis.
      PATIENTS: 36 children (12 with grass pollen, 12 with ragweed pollen
      immunotherapy, 12 controls). METHODS: nasal provocation tests with increasing
      doses of Allerkin, skin prick test, diary cards. Schedule of the investigations:
      enrollment of the patients and nasal provocation tests; grass pollen and ragweed
      pollen preseasonal immunotherapy with increasing doses of Allerkin; during pollen
      season registration by symptoms and drug consumption; after the season nasal
      provocation tests. RESULTS: grass immunotherapy: nasal provocation threshold
      increased (P < 0.01), symptoms became fewer (P < 0.01) and drug consumption was
      less in the active group compared to control. Similar but less expressed
      tendencies were seen in the ragweed group. After the second year of immunotherapy
      the need for steroid treatment was significantly (P < 0.05) fewer in the
      immunotherapy group than in the control group. No side effects appeared during
      the course of immunotherapy, but some patients suffered from mild sneezing or
      nasal discharge after the Allerkin application. CONCLUSION: local (nasal)
      immunotherapy is an effective, safe and not troublesome alternative to systemic
      immunotherapy.

PMID- 9188950
TI  - Ultrastructural localization of histamine in human basophils and mast cells;
      changes associated with anaphylactic degranulation and recovery demonstrated with
      a diamine oxidase-gold probe.
AB  - Subcellular sites of histamine in purified human lung mast cells and human
      peripheral blood basophils were determined using a newly developed enzyme-gold
      affinity method for ultrastructural analysis. The evolving morphologies of
      regulated secretion and recovery from regulated secretion in each cell showed
      that granule stores of histamine were released at early times after stimulation
      and re-accumulated at later times post-stimulus. Renewal of histamine granule
      stores occurred by multiple mechanisms including synthesis and conservation of
      granule materials and membranes.

PMID- 9188951
TI  - Molecular events in allergic inflammation: experimental models and possible
      modulation.
AB  - In recent years, a complex molecular network involving cytokines kinins and
      adhesion molecules has been demonstrated to operate in allergic inflammation. In
      particular, the adhesion machinery plays a crucial role for the recruitment and
      locomotion of the inflammatory cells and the Intercellular Adhesion Molecule 1
      (ICAM-1) is a hallmark of the allergic inflammatory process. The role and
      possible modulation of ICAM-1 can be investigated using both eye and nose
      experimental models. Conjunctival and nasal epithelium are easy to study either
      under natural allergen exposure or after specific/aspecific provocation tests;
      furthermore the nasal/conjunctival challenge is well tolerated by the patients.
      These experimental models have allowed us to investigate in vivo the antiallergic
      properties of several compounds. Many of the new antihistamines, but also
      deflazacort and local nasal immunotherapy, were demonstrated capable of reducing
      both inflammatory infiltration and ICAM-1 expression on epithelia. Because of the
      central role of adhesion molecules in allergic inflammation, their
      pharmacological modulation can be regarded as a promising therapeutic approach.

PMID- 9188952
TI  - The role of basophils and mast cells in acute and late reactions in the skin.

PMID- 9188953
TI  - The eosinophil and the eye.
AB  - Personal studies in allergic eye diseases reviewed in this paper indicate that:
      1. An increased number and an abnormal distribution of eosinophils is present in
      conjunctival biopsies of patients with vernal keratoconjunctivitis (VKC). 2.
      Eosinophil and eosinophil products, such as ECP, are also increased in tears of
      VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase
      of allergic reaction following specific allergen challenge. 3. Circulating
      eosinophils of VKC patients show a typical activation phenotypic profile which is
      associated with increased serum level of eosinophil cationic protein and
      eosinophil-derived neurotoxin/protein X. A clinical study of the modulatory
      effect of cetirizine on the early and late phase of the allergic reaction as well
      as on the eosinophil activation and tissue recruitment following conjunctival
      allergen challenge is reported as an example of the need to evaluate eosinophil
      functions when investigating anti-allergic drugs. Drugs modulating various
      aspects of eosinophil function could play a primary role in the treatment of
      allergic eye disease.

PMID- 9188954
TI  - Purine derivatives in the study of allergic inflammation in respiratory diseases.
AB  - Adenosine, a naturally occurring purine nucleoside, elicits dose-related
      bronchoconstriction in asthmatic subjects when administered by inhalation and it
      is recovered in increased amounts from the bronchial lavage fluid of subjects
      with active asthma when compared to normal controls. Although the mechanism by
      which adenosine mediates bronchoconstriction in asthmatic subjects is not clear,
      recent data indicate an important role for mast cell mediator release. We have
      recently shown that local airway challenge with adenosine in subjects with asthma
      and rhinitis provokes an increase in the levels of PGD2, histamine and tryptase.
      However, airway responsiveness and atopic status are the most important
      determinants of adenosine-induced responses, regardless of any increases in mast
      cell mediators in airway fluids. New discoveries suggest that the airway response
      to adenosine may be an index of mast cell priming and therefore may provide a
      useful tool to further explore the inflammatory processes in allergic asthma and
      rhinitis. Therefore adenosine provocation may gain increasing acceptance as an
      additional measure of disease activity in asthma and rhinitis.

PMID- 9188955
TI  - Antihistamines in the treatment of asthma.
AB  - Antihistamines were investigated for use in asthma shortly after discovery over
      fifty years ago. Earlier compounds proved ineffective because of side effects:
      this class of drugs was not thought useful for asthma, and were actually
      considered contraindicated. More recent drugs have greater potency, fewer side
      effects, and no evidence of adverse effects in asthma. There are some studies
      showing second generation antihistamines, especially cetirizine, improve certain
      parameters of asthma.

PMID- 9188956
TI  - Highlights in cardiovascular effects of histamine and H1-receptor antagonists.
AB  - Despite numerous studies, the cardiac actions of histamine are still obscure.
      Yet, histamine could probably be clinically relevant. It is stored in large
      amounts in human cardiac tissue, where it is contained in the cytoplasmatic
      granules of mast cells. Mast cells are present in normal human heart tissue; they
      are more abundant in diseased human heart tissue where they lie in close
      proximity to blood vessels and between myocytes. The histamine content of human
      heart mast cells is comparable to the histamine content of lung parenchymal and
      skin mast cells. Ultrastructural studies confirmed the presence of mast cells
      around vessels and between myocytes. Consequently, these cells are easily
      accessible to circulating antigens, drugs and stimuli that activate the cells to
      release vasoactive mediators which in turn can exert significant cardiovascular
      effects. Histamine possesses arrhythmogenic effects and once locally released,
      may enhance automaticity and induce triggering activity resulting in severe
      tachyarrhythmias. The major arrhythmogenic effects of histamine consist in
      increasing sinus rate and ventricular automaticity, and in slowing
      atrioventricular conduction. In addition, histamine may interfere with
      depolarization and repolarization through its effects on calcium and potassium
      currents. These effects are mediated by H2-receptor. Therefore direct activation
      of histamine receptor can induce cardiac arrhythmias. Consequently, the
      interference of these histaminergic effects may explain, at least in part, the
      arrhythmogenic effects described for some second-generation antihistamines, such
      as terfenadine and astemizole. In this brief review we will discuss the cardiac
      effects of histamine in experimental animal models and in man, and will review
      data on the safety of the new second-generation antihistamines, focusing on their
      cardiotoxic effects.

PMID- 9188957
TI  - Anterior arch adjustment.

PMID- 9188958
TI  - Basic concepts concerning bracket failure research.

PMID- 9188959
TI  - Bond strength following the application of chlorhexidine on etched enamel.
AB  - The purpose of this study was to determine whether the application of
      chlorhexidine to etched enamel affects the shear bond strength and
      bracket/adhesive failure modes of orthodontic brackets. Forty recently extracted
      third molars were cleaned divided into two groups of twenty. The first group was
      etched with a 37% phosphoric acid gel, and a sealant was applied containing a
      chlorhexidine varnish. Stainless steel orthodontic brackets were bonded using the
      Transbond XT bonding system (3M/Unitek). Teeth in the second group were etched
      and bonded using the same bonding system but without chlorhexidine. A Zwick
      Universal Testing Machine was used to determine shear bond strengths. There were
      no significant differences in bond strengths between the chlorhexidine treated
      teeth (= 11.8 +/- 2.1 MPa) and the controls (= 12.4 +/- 3.1 MPa) (p = 0.129). The
      Chi Square test evaluating the residual adhesive on the enamel surfaces showed no
      significant differences (P = 0.136) between the two groups evaluated. The use of
      a primer containing chlorhexidine does not significantly affect shear bond
      strength nor the fracture site (bond failure location).

PMID- 9188960
TI  - Bond strengths of two ceramic brackets using argon laser, light, and chemically
      cured resin systems.
AB  - The present study compared tooth-bracket bond strengths using two types of
      ceramic brackets and three methods of polymerization: argon laser, conventional
      light, and chemical. Ninety extracted human premolars were prepared for bonding
      with pumice and gel etchant. Using single crystal alumina brackets with silanated
      bases, three groups of 15 teeth were bonded with one of the three polymerization
      methods. Similarly, three groups of 15 teeth were bonded with polycrystal alumina
      brackets with nonsilanated bases. Each bonded bracket was tested on an Instron
      tensile testing machine in shear mode to determine shear debonding strength.
      Fracture sites were recorded. Results demonstrated that (1) all combinations
      produced shear bond strengths greater than those considered clinically
      acceptable, (2) the mean shear bond strengths of the single crystal alumina
      brackets with silanated bases were significantly higher than those of the
      polycrystal alumina brackets with nonsilanated bases, and (3) no enamel fractures
      were found on debonding the chemically cured brackets while the light and laser
      groups exhibited a 10% rate of enamel fracture on debonding.

PMID- 9188961
TI  - Evaluation of the shear bond strength of different ceramic bracket base designs.
AB  - The purpose of this study was to compare the Ceramaflex bracket with a
      traditional ceramic orthodontic bracket with regard to shear bond strength and
      bond failure location. Forty newly extracted human premolars were randomly
      divided into two groups. Twenty Ceramaflex brackets (TP Orthodontics Inc,
      LaPorte, Ind) and 20 Transcend 6000 brackets (Unitek Corp, Monrovia, Calif) were
      bonded to the teeth using the same bonding system (Right On, TP Orthodontics Inc,
      LaPorte, Ind). A Zwick Universal Test machine (Zwick Gm bH & Co, Ulm, Germany)
      was used to determine the shear bond strength for each bracket. After debonding,
      the teeth and brackets were examined under 10x magnification. After debonding,
      the amount of resin material adhering to the enamel surface was assessed
      according to the Adhesive Remnant Index (ARI). The results of this study suggest
      that Ceramaflex brackets have a significantly lower bond strength than
      traditional ceramic brackets. On the other hand, the bond failure location of the
      Ceramaflex bracket was consistently more favorable, i.e., occurring at the
      ceramic bracket-polycarbonate base.

PMID- 9188962
TI  - Orthodontic bonding to Adlloy-treated type IV gold.
AB  - Adlloy surface treatment of noble alloys has been shown to increase the bond
      strength of composite to gold alloys. The purpose of this study was to test the
      bond strength of Adlloy-treated type IV gold surfaces and orthodontic brackets
      bonded with self-curing composite resin, and compare it with sandblasted gold and
      etched enamel. Data were derived from a control sample of 40 human premolars and
      two experimental groups of Adlloy-treated and sandblasted gold surfaces. "A"
      Company premolar brackets were bonded with Concise self-curing composite resin.
      The specimens were submerged in water for 30 days and thermocycled 1500 times
      before being subjected to shear bond tests. Statistically significant differences
      were found in the mean values of the three groups (F = 124.04; df = 2,117; P <
      .001). Bonds on the adlloy-treated gold were twice as strong as those found on
      microetched gold. Adlloy surface treatment of type IV gold will permit adequate
      bond strength; however, FDA approval is required for intraoral use.

PMID- 9188963
TI  - Evaluation of a resin-reinforced glass ionomer cement for use as an orthodontic
      bonding agent.
AB  - A resin-reinforced glass ionomer cement, distributed commercially as "Fuji Ortho"
      (FO), has recently been developed for orthodontic bracket bonding procedures. The
      purposes of this study were to determine the tensile and shear bond strength of
      FO, to measure the amount of cement remaining on the enamel after bracket
      removal, and to evaluate the effects of experimental strain on the enamel
      surface. SEM evaluation demonstrated that polishing with 2400-grit waterproof
      abrasive paper followed by treatment with polyacrylic acid produced a smooth
      enamel surface without debris. No significant differences were seen in bond
      strengths between 24 hours and thermal cycling. Tensile and shear strengths of FO
      were significantly higher after thermal cycling than with conventional glass
      ionomer cement, at 3.4 +/- 0.7 MPa and 17.9 +/- 4.5 MPa, respectively. The
      adhesive Remant Index (ARI) indicated that FO adhered firmly to the unetched
      enamel surface and its scores showed 2 to 3 after thermal cycling. Results of
      this investigation suggest that FO may serve as an advantageous alternative to
      composite resin for the bonding of orthodontic brackets.

PMID- 9188964
TI  - A review of contemporary archwires: their properties and characteristics.
AB  - The materials used by orthodontists have changed rapidly in recent years and will
      continue to do so in the future. As esthetic composite archwires are introduced,
      metallic archwires will likely be replaced for most orthodontic applications in
      the same way that metals have been replaced by composites in the aerospace
      industry. Archwires are reviewed in the order of their development, with emphasis
      on specific properties and characteristics, such as strength, stiffness, range,
      formability, and weldability. Because an ideal material has not yet been found,
      archwires should be selected within the context of their intended use during
      treatment.

PMID- 9188965
TI  - Stiffness-deflection behavior of selected orthodontic wires.
AB  - Treatment of horizontal and vertical tooth discrepancies requires wires of low
      stiffness to produce forces as the teeth are leveled and aligned. In this
      investigation, the stiffness characteristics of several solid and multistrand
      nickel-titanium and stainless steel orthodontic wires were determined at selected
      clinically relevant deflections. Twenty specimens of 24 different wires were
      tested in both three-point and three-bracket bending modes. The unloading force
      deflection plot of each wire was described by a polynomial regression from which
      wire stiffnesses were obtained by mathematical differentiation. Graphs of the
      functional relationship between stiffness and deflection are presented. The
      results of this investigation show that wire stiffness can be altered not only by
      changing the size, but also by varying the number of strands and the alloy
      composition. An equally important finding was the dependence of stiffness on
      deflection for most of the wires measured. Comparisons were also made between the
      stiffness values obtained in three-point bending and the three-bracket bending
      systems.

PMID- 9188966
TI  - Variable modulus orthodontics advanced through an auxiliary archwire attachment.
AB  - Reducing the load deflection rates of orthodontic springs is important, for it
      provides relative constancy of the moment-to-force ratio applied to the teeth
      with concomitant, forecastable dental movement. Increasing patient comfort and
      reducing the number of office visits while lowering potential tissue damage are
      additional features of lower load deflection rate springs. A simple auxiliary
      attachment, which can be crimped into position on an archwire or onto segments of
      an archwire, is described. This attachment permits the clinician to incorporate a
      relatively high rate stiff wire to enhance the anchorage of the reactive teeth in
      one area of the dental arch, while allowing the use of lesser stiffness (lower
      load deflection rate spring) to engage teeth targeted for movement. The auxiliary
      allows the clinician various stiffness through the use of wire of one modulus
      (stainless steel, for example) in one area of the arch, and wire of a differing
      modulus (NiTi, for example) in another area of the same arch. The advantages and
      disadvantages of choosing wires of differing moduli are reviewed. Alternative
      methods of transforming the spring rate through changes in wire cross-section or
      length are also reviewed. Practical clinical applications of the auxiliary
      attachment are shown.

PMID- 9188967
TI  - Comparison of occlusal contacts with use of Hawley and clear overlay retainers.
AB  - Following orthodontic treatment, an increase in the number of occlusal contacts
      is usually desired during retention. In this study, Hawley and clear overlay
      orthodontic retainers were compared relative to changes in the number of occlusal
      contacts. Occlusal contacts were quantified in 30 orthodontic patients at
      debonding, at retainer delivery, and after 3 months of retention. The paired t
      test was applied to evaluate longitudinal changes in the number of and intensity
      of contacts. Results show that with the Hawley retainer there was a significant
      increase in occlusal contacts on posterior teeth and no change on anterior teeth.
      With the clear overlay retainer there was no significant change in either
      posterior or anterior contacts during retention. The retentive capacities of the
      two retainers differ: the Hawley retainer allows relative vertical movement
      (settling) of the posterior teeth while the clear overlay retainer holds teeth in
      their debanding position.

PMID- 9188968
TI  - The effect of acetaminophen on tooth movement in rabbits.
AB  - Orthodontic patients have reported the use of analgesics during therapy. However,
      common anti-inflammatory analgesics, such as aspirin and ibuprofen, have been
      shown to slow the rate of tooth movement. Acetaminophen, another common
      analgesic, does not possess anti-inflammatory properties. The effect of
      acetaminophen on tooth movement was studied using New Zealand white rabbits.
      Experimental animals were matched to a control animal of the same sex and weight.
      Under anesthesia, springs were ligated between the lower first molar and incisor,
      resulting in approximation of these teeth. Under blinded conditions, seven of the
      rabbits received 1000 mgs of acetaminophen daily. Seven control animals received
      water. The animals were sacrificed after 21 days. The movement of incisors and
      molars was measured. Results showed considerable movement within both the
      experimental and control groups, but no significant difference in tooth movement
      between them. Acetaminophen has no effect on the rate of tooth movement in
      rabbits undergoing orthodontic treatment.

PMID- 9188969
TI  - Cherubism: presentation of a case.
AB  - Cherubism is a rare, fibro-osseous bone disease that affects the jaws. Bilateral
      enlargement of the mandible produces a full, round lower face. The skin over the
      cheeks stretches and pulls the lower eyelids down, exposing a thin line of sclera
      and eyes that are raised, seemingly heavenward. The patient in this report was
      diagnosed but not treated.

PMID- 9188970
TI  - Vacuum-assisted closure: a new method for wound control and treatment: animal
      studies and basic foundation.
AB  - A series of basic animal studies using a new subatmospheric pressure technique
      (The V.A.C.) to expedite wound healing are presented. The technique entails
      placing an open-cell foam into the wound, sealing the site with an adhesive
      drape, and applying subatmospheric pressure (125 mmHg below ambient) that is
      transmitted to the wound in a controlled manner. Utilizing a pig model, four
      studies were undertaken to determine the effect of subatmospheric pressure on
      laser Doppler-measured blood flow in the wound and adjacent tissue (N = 5), rate
      of granulation tissue formation (N = 10), clearance of bacteria from infected
      wounds (N = 5), and measurement of nutrient flow by random-pattern flap survival
      (N = 5). Blood flow levels increased fourfold when 125 mmHg subatmospheric
      pressure was applied. Significantly increased rates of granulation tissue
      formation (p < or = 0.05) occurred with both continuous (63.3 +/- 26.1%) and
      intermittent (103% +/- 35.3%) application. Tissue bacterial counts significantly
      decreased (p < or = 0.05) after 4 days of application. Random-pattern flap
      survival significantly increased (p < or = 0.05) by 21% compared to controls. We
      determined that the application of controlled subatmospheric pressure creates an
      environment that promotes would healing.

PMID- 9188971
TI  - Vacuum-assisted closure: a new method for wound control and treatment: clinical
      experience.
AB  - Despite numerous advances, chronic and other difficult-to-manage wounds continue
      to be a treatment challenge. Presented is a new subatmospheric pressure
      technique: vacuum-assisted closure (The V.A.C.). The V.A.C. technique entails
      placing an open-cell foam dressing into the wound cavity and applying a
      controlled subatmospheric pressure (125 mmHg below ambient pressure). Three
      hundred wounds were treated: 175 chronic wounds, 94 subacute wounds, and 31 acute
      wounds. Two hundred ninety-six wounds responded favorably to subatmospheric
      pressure treatment, with an increased rate of granulation tissue formation.
      Wounds were treated until completely closed, were covered with a split-thickness
      skin graft, or a flap was rotated into the health, granulating would bed. The
      technique removes chronic edema, leading to increased localized blood flow, and
      the applied forces result in the enhanced formation of granulation tissue. Vacuum
      assisted closure is an extremely efficacious modality for treating chronic and
      difficult wounds.

PMID- 9188972
TI  - Pediatric facial fractures: a demographic analysis outside an urban environment.
AB  - This study reviews all pediatric facial fractures treated operatively at the C.S.
      Mott Children's Hospital of the University of Michigan over a 5-year period.
      Previous series of pediatric facial fractures have been collected at large urban
      centers and may not be representative of all practice environments. Our
      institution is a level 1 trauma center that serves a patient population primarily
      from suburban and rural regions throughout the state. Referral and practice
      patterns at our institution gave us an important opportunity to analyze
      differences in patient care and management secondary to venue, and challenge the
      assumptions made by studies collected at large urban centers. We reviewed 80
      fractures in 62 patients. Patient age ranged from 2 to 18 years old with the
      majority of patients (58%) between 15 and 18 years old. Most fractures resulted
      from motor vehicle accidents (43%) and there were no firearm injuries. Fracture
      sites included the mandible (38%), the frontonasoethmoid region (35%), the
      midface (17%), and the orbit (10%). Only two operative complications were
      reported. There were no cervical spine injuries. Median patient age was higher
      and mechanism of injury differed in our study compared with urban studies. Rapid
      changes in the health care delivery system and the emergence of managed care
      demand accurate demographic updates for the efficient allocation of valuable
      resources. Our results showed important differences with previous studies and
      imply that assumptions and analysis of the care of pediatric facial fractures
      based solely on data collected at large urban centers may be too parochial, and
      therefore subsequent health care decisions of resource allocation arrived at
      without respect to practice environment could be erroneous.

PMID- 9188973
TI  - Free latissimus dorsi muscle transfer using an endoscopic technique.
AB  - Endoscopic techniques in plastic surgery have involved aesthetic procedures such
      as facelift, breast augmentation, abdominoplasty, and placement of tissue
      expanders. Recently, endoscopic harvest of the donor tissue for free flap
      transfer has included the omentum, jejunum, latissimus dorsi muscle, and rectus
      abdominis muscle. Ten patients with a soft-tissue defect in the lower extremity
      were successfully reconstructed from December 1994 to October 1995 with a free
      muscle transfer after endoscopic harvest of the latissimus dorsi muscle. Nine
      patients were male and 1 patient was female. A 5- to 6-cm incision was initially
      made along the posterior axillary line, allowing direct identification of the
      thoracodorsal vascular pedicle. The latissimus dorsi muscle was dissected
      posteriorly until the limits of open dissection were reached, and then the
      dissection was continued under endoscopic visualization. The largest harvested
      muscle was 15 x 25 cm in size. Follow-up ranged from 6 to 15 months. We believe
      that plastic surgeons can take advantage of endoscopic techniques to obtain
      reliable and safe results, with smaller scars and reduced postoperative donor
      site morbidity such as pain and wound-healing problems. This technique may prove
      particularly applicable to women, children, and patients who are prone to
      hypertrophic scars.

PMID- 9188974
TI  - Seroma as a common donor site morbidity after harvesting the latissimus dorsi
      flap: observations on cause and prevention.
AB  - This prospective study reveals that the incidence of seroma formation after
      harvesting the latissimus dorsi muscle by scalpel is reasonably moderate. This
      incidence is lower when the resulting skin flaps are tacked to the underlying
      structures with resorbable sutures. In contrast, electrocautery dissection shows
      a significantly much higher rate of seroma formation, probably because of thermal
      injury of the wide fascial wound layers or the subcutaneous fat tissue. Fifty
      eight patients were distributed among three groups. Within each group a specific
      way of latissimus dorsi muscle harvesting and donor site treatment was
      accomplished. The group of scalpel dissection and skin flap fixation to the
      underlying layers with additional tacking sutures shows the lowest rate of seroma
      formation (9.1%, N = 2) due to the avoidance of shearing effects. A clearly
      higher incidence is present in the group of scalpel dissection without tacking
      sutures (38.1%, N = 8), whereas seromas most frequently result after
      electrocautery dissection without skin flap fixation (80.0%, N = 12).

PMID- 9188975
TI  - Reconstruction of posttraumatic defects of the foot by flow-through anterolateral
      or anteromedial thigh flaps with preservation of posterior tibial vessels.
AB  - Massive posttraumatic defects of the foot in 4 patients and a tibial malunion in
      another were repaired by flow-through anterior (anterolateral and anteromedial)
      thigh flaps. Posterior tibial vessels were used as the recipient vessel just
      below the level of the medial malleolus. Soft-tissue defects in foot-injured
      patients were covered with flow-through anterior thigh flaps interposing the
      descending branch of the lateral circumflex femoral system between the transected
      posterior tibial vessels. In another patient, a combined anteromedial thigh flap
      and vascularized iliac bone cross-leg "chimeric" flap were successfully
      transferred for the reconstruction of a malunion of a tibial fracture, which had
      been accompanied by severe vascular damage to the thigh. The utilization of
      derivative branches from the lateral circumflex femoral system facilitates
      revascularization of ischemic areas and simultaneous transplantation of multiple
      components, as well as preserves recipient vessels. Owing to the stable blood
      supply, these flaps can be readily processed into both deepithelialized and thin
      flaps.

PMID- 9188976
TI  - An anatomic comparison of septocutaneous free flaps from the thigh region.
AB  - Various free flaps have been utilized in the thigh region, however there are few
      systematic clinicoanatomic studies of the thigh region. The purpose of this study
      is to clarify the clinicoanatomic characteristics of the free septocutaneous
      thigh flap. Forty-two dissections were carried out in unenbalmed cadavers. The
      pedicle was observed in all specimens in the anterolateral thigh (ALT), medial
      thigh, gluteal thigh, and lateral thigh flaps. The pedicle was observed in 46% of
      the specimens in the anteromedial thigh flap. The pedicle was observed in 86% of
      the specimens in the posterior thigh flap. The pedicle length (153 +/- 23 mm) of
      the ALT flap was the longest pedicle in the thigh flaps. The internal diameter of
      the pedicle of the ALT flap (3.0 +/- 1.0 mm), which could be used for
      anastomosis, is the largest in the septocutaneous thigh flaps. The
      clinicoanatomic characteristics of thigh flaps are clarified.

PMID- 9188977
TI  - Free tissue transfer in treatment of the recalcitrant chronic venous ulcer.
AB  - We propose that a long-term cure for the recalcitrant chronic venous ulcer must
      involve a dual surgical approach including (1) wide excision of the ulcer and
      surrounding liposclerotic tissue bed, and (2) replacement by a free flap
      containing multiple, competent microvenous valves with a normal microcirculation.
      Advantages of free flaps over skin grafting include improvement of the underlying
      pathophysiology; increase in blood supply to the area; ability to cover exposed
      bone, joint, or tendon; and a lower incidence of recurrence. During the past 8
      years, 20 consecutive muscle free flaps were performed in 18 patients for 19
      recalcitrant venous ulcers (two "sequential" flaps to the ipsilateral leg in 1
      patient and a repeat flap after initial failure in 1 patient). Twelve males and 6
      females ranged in age from 17 to 76 years (mean, 44 years). Nontraumatic,
      nonosteomyelitic venous ulcers had been present for an average of 3.5 years
      (range, 1-10 years) and failed an average of 2.4 skin grafts (range, 0-6 grafts).
      Defects ranged from 100 to 600 cm2 (mean, 238 cm2). Donor tissues included rectus
      abdominis (N = 13), latissimus dorsi (N = 5), gracilis (N = 1), and serratus (N =
      1) muscles. Recipient vessels included posterior tibial (N = 12), anterior tibial
      (N = 6), and peroneal (N = 2). In all instances except one, only one vein,
      usually one of the venae comitantes, was anastomosed in end-to-end fashion.
      Successful free tissue transfer was accomplished in 18 of 20 flaps (90%).
      Complications included infection with partial flap and/or skin graft loss (three
      flaps), and partial skin graft loss (two flaps). There were no recurrences within
      the flaps; however, breakdown occurred at the junction between the flap and
      residual adjacent liposclerotic skin in 1 patient. Follow-up average 32.7 months
      (range, 8-65 months); 3 patients were lost to follow-up. Free muscle transfer can
      provide a long-term cure for the recalcitrant venous ulcer by replacing the
      diseased tissue bed with healthy tissue containing multiple, competent
      microvenous valves and a normal microcirculation. This can be accomplished in one
      reconstructive procedure with excellent long-term results.

PMID- 9188978
TI  - Rectus abdominis muscle transplant in lower limb salvage: a recent series of 25
      patients.
AB  - A recent series of 25 patients who underwent reconstruction of Gustilo IIIB lower
      extremity wounds with rectus abdominis muscle transplants is presented.
      Complications include one flap loss and one donor site skin incision dehiscence.
      At follow-up, a majority of patients were ambulatory and a third employed in some
      fashion. Comparison with a historical group of patients demonstrates continued
      improvement in surgical results.

PMID- 9188979
TI  - The relative importance of intramedullary, intracortical, and extraosseous soft
      tissue blood flow to the repair of devascularized canine tibial cortex.
AB  - Previous studies have not quantified the relative contributions of intracortical
      and extracortical perfusion to cortical porosity and new bone formation. The
      current study was performed to determine the relative importance of
      intramedullary, intracortical, and extraosseous soft-tissue blood flow and type
      of tissue to the repair of devascularized canine tibial cortex. A 2.5-cm segment
      of tibia between two standardized osteotomies was devascularized. The segment was
      replaced anatomically and stabilized with a plate. The animals were divided
      randomly into two groups: skin coverage (N = 8) and muscle coverage (N = 8).
      Thirty-one days postoperatively, cerium141 microspheres were injected, prior to
      sacrifice, to measure blood flow. Extraosseous soft-tissue perfusion was the same
      in the skin coverage and muscle flap coverage groups. There was no relationship
      between intramedullary or extraosseous soft-tissue flow and depth of new bone
      formation and cortical porosity. Intracortical blood flow was directly related to
      depth of new bone formation (p = 0.0006) and cortical porosity (outer cortex, p =
      0.001; inner cortex, p = 0.0001). These findings indicate that the cortical
      repair process is linked to the restoration of perfusion and that muscle
      coverage, rather than the quantity of blood flow, determines the extent of
      cortical repair.

PMID- 9188980
TI  - Bead and wire intermaxillary fixation.
AB  - We have developed a method of intermaxillary fixation using beads and wires. This
      method was effective in mandibular fractures that underwent both open and closed
      reduction. Our procedure is simple, requires little time, and is inexpensive. We
      also found several advantages of our technique when compared with the classic
      arch bar, wire, and eyelet method of intermaxillary fixation.

PMID- 9188981
TI  - Reverse pedicled lateral arm flap for reconstruction of posterior soft-tissue
      defects of the elbow.
AB  - Posterior soft-tissue defects of the elbow are difficult to reconstruct by
      conventional techniques such as closure by approximation or skin graft. An ideal
      technique should be an easy and reliable one-stage procedure that provides
      predictable surgical results with regard to elbow function and cosmesis. This
      report details our experience in 7 patients who underwent a one-stage procedure
      for coverage of the posterior elbow employing the reverse pedicled lateral arm
      flap. All flaps survived and all patients were able to resume full range of
      motion of the elbow joint at the 6-month follow-up. Complications included
      forearm paraesthesia in 3 patients and conspicuous scarring in a young female
      patient. We emphasize two valuable refinements in surgical technique including
      measuring posterior elbow defect in full flexion and postoperative elbow
      extension splinting. In trauma-related defects of the posterior elbow, a
      preoperative angiogram is important before raising this flap.

PMID- 9188982
TI  - Small intestinal perforation and peritonitis after abdominal suction lipoplasty.
AB  - Suction lipoplasty for abdominal contouring in nonoperated patients is considered
      a safe procedure with a low incidence of local and systemic complications.
      Suction lipoplasty combined with a full abdominoplasty is, however, still
      controversial with a higher rate of local complications. A 56-year-old woman with
      a history of four laparotomies and two abdominoplasties was hospitalized with
      abdominal pain and signs of peritonitis after an ambulatory suction lipoplasty.
      During laparotomy for peritonitis the abdominal wall was found to be stiff and
      fibrotic, with massive adhesions to the intestine. Two small intestinal
      perforations caused soiling into the peritoneum. The perforated intestinal
      segment was resected and the postoperative history was uneventful. Both recent
      and former laparotomies in the lower abdomen represent a possible risk when
      suction lipoplasty is performed. An ultrasonographic or computed tomographic scan
      of the abdominal wall would identify or rule out any underlying fascial defect or
      hernia.

PMID- 9188983
TI  - Subcutaneous metallic mercury injection: early, massive excision.
AB  - The case of a patient who injected 10 cc of metallic mercury subcutaneously into
      his left forearm through multiple punctures in an attempt at suicide is
      presented. Diagnosis was made by plain radiography of his left forearm, which
      exhibited redness, edema, and tenderness on the third day postinjection. Early
      excision of all affected subcutaneous tissues including metallic mercury deposits
      was performed on the fifth day postinjection. Blood and urine mercury levels that
      were initially found in high levels decreased dramatically to normal ranges after
      the excision and remained unchanged at the follow-up period of 6 months. No renal
      or hepatic functional impairment was encountered. The patient was free of toxic
      symptoms and mercury embolism. The local, aseptic lytic property of metallic
      mercury, which could cause severe damage to vital structures, was observed
      perioperatively. Early diagnosis and early, massive excision of mercury deposits
      in affected tissues is the important treatment modality in these rare cases.

PMID- 9188984
TI  - Adipofascial flap harvest using endoscopic assistance.
AB  - Minimally invasive plastic surgery has expanded beyond the original confines of
      aesthetic applications to encompass all our endeavors in an attempt to restrict
      the size of surgical scars, limit postoperative discomfort, and hasten recovery
      of function. This evolution has already delineated methods to raise our workhorse
      muscle flaps and has negated the risks of laparotomy for various visceral flaps.
      It is then only a logical progression to use these endoscopic techniques to
      harvest fascial flaps so as to avoid the notorious donor site morbidity of the
      fasciocutaneous flap, which has certainly hindered the rapid acceptance of these
      otherwise valuable flaps. Endoscopic-facilitated elevation of a local
      adipofascial flap is described for which little or no additional skin incisions
      need ever be made.

PMID- 9188985
TI  - Squamous cell carcinoma in perineal inflammatory disease.
AB  - Four patients with squamous cell carcinoma of the perineal region were diagnosed
      and treated during the last 4 years in our institutions. The underlying diagnoses
      consisted of recurrent pilonidal disease, Crohn's disease, and hidradenitis
      suppurativa. In all patients, a pattern of a long-term inflammatory process was
      evident. Current concepts regarding the pathophysiology of a chronic inflammatory
      state and malignant transformation are reviewed. We conclude that regardless of
      the original pathology, all chronic inflammatory processes in the perineal region
      should be evaluated for malignant degeneration. A high index of suspicion may
      potentiate an early diagnosis, possibly improving the chance of cure.

PMID- 9188986
TI  - Granular cell tumor of uncertain malignant potential.
AB  - Granular cell tumor is an uncommon soft-tissue tumor that is usually benign and
      readily treated with complete resection. Malignant granular cell tumors are
      perhaps the rarest of all soft-tissue tumors, and they commonly metastasize to
      regional lymph nodes and the lungs. We present a case of granular cell tumor that
      exhibited both gross and microscopic features suggestive of malignancy without
      evidence of metastasis through a relatively short 16 months of follow-up and
      review the literature pertaining to granular cell tumors of uncertain malignant
      potential.

PMID- 9188987
TI  - Late recurrence of malignant melanoma and second primary malignant melanoma: a
      report of 3 patients.

PMID- 9188988
TI  - Immunohistochemical localization of nerve fibres during development of embryonic
      rat molar using peripherin and protein gene product 9.5 antibodies.
AB  - Nerve fibres were localized during the initiation and early morphogenesis of the
      first molar tooth in rat embryos by immunoperoxidase detection of the
      intermediate-filament protein peripherin and protein gene product 9.5 (PGP 9.5).
      Nerve fibres from the trigeminal ganglion were detected in the developing first
      branchial arch of E12-14 embryos. Nerves were not seen in the vicinity of the
      developing tooth germ before the buid stage (E15), when they were seen around the
      condensed dental mesenchyme. During transition from the bud to the cap stage
      (E15), nerve fibres were detected not only in the area of the future dental
      follicle but also in the mesenchyme next to dental epithelium on the buccal side
      of the tooth germ. During later cap and bell stages nerve fibres persisted in the
      dental follicle, but they were not seen in the epithelial dental organ or dental
      papilla mesenchyme. Absence of trigeminal nerve fibres from the presumptive tooth
      bearing area indicates that they are not involved in the initiation of rat tooth
      development. In addition, the localization of nerve fibres shows that there are
      some differences in the innervation of rat teeth compared with human and mouse
      teeth. These results provide data for further studies on the regulation of
      embryonic rat tooth innervation.

PMID- 9188990
TI  - Enhancement by conditioned medium of stretched calvarial bone cells of the
      osteoclast-like cell formation induced by parathyroid hormone in mouse bone
      marrow cultures.
AB  - To investigate whether mechanical deformation of osteoblasts exerts an influence
      upon parathyroid hormone (PTH)-induced bone resorption, the effect of medium
      conditioned by a statistically stretched, osteoblast-enriched, bone cell
      population on PTH-induced osteoclast-like cell formation in mouse bone marrow
      cultures was examined. The conditioned medium of stretched cultures stimulated
      bone marrow cells to differentiate into tartrate-resistant acid phosphatase
      (TRAP)-positive multinuclear cells in the presence of 10(-8) M PTH(1-34). The
      stimulatory effect of the conditioned medium was significant when the bone cells
      were stretched at 2 mm deflection in the 90% subconfluent state. Conditioned
      medium from cultures in the 50% subconfluent state failed to enhance osteoclast
      like cell formation. PTH-induced, TRAP-positive multinuclear cells were decreased
      in number by the addition of stretch-conditioned medium in the postconfluent
      state. When 10(-6) M indomethacin was added to bone cell cultures during
      stretching, the resulting conditioned medium suppressed PTH-induced, TRAP
      positive multinuclear cell formation. However, even if 10(-8) M prostaglandin E2
      was added to the stretched bone cell cultures along with the indomethacin, the
      resulting conditioned medium did not reverse the suppression of the PTH-induced,
      osteoclast-like cell formation. These findings suggest that bone resorption in
      response to continuous mechanical deformation is regulated by cells of the
      osteoblast lineage such as preosteoblasts, osteoblasts, bone lining cells and
      osteocytes in vivo, and that prostaglandins, but not prostaglandins E2, are
      involved in the stretch-enhanced, osteoclast-like cell formation.

PMID- 9188989
TI  - Expression of vasoactive intestinal polypeptide receptor mRNA and secretory
      regulation by vasoactive intestinal polypeptide in rat submandibular and
      sublingual salivary glands.
AB  - Vasoactive intestinal polypeptide (VIP)-receptor mRNA was strongly expressed in
      the acinar cells in the submandibular gland but not in the sublingual gland. VIP
      containing nerve fibres were richly distributed around acini in the submandibular
      gland but were rare around acini of the sublingual gland. In the submandibular
      gland, the chorda was stimulated at various frequencies (1-40 Hz) together with
      an infusion of (N-Ac-Tyr1, D-Phe2)-GRF(1-29)-NH2 (109 M), VIP antagonist, which
      reduced salivary flow from the submandibular gland only at high-frequency
      stimulation (> 20 Hz), and more markedly reduced the salivary protein
      concentration. When the chorda was continuously stimulated the antagonist reduced
      the salivary flow only during the initial 5 min. Exogenous VIP 10(-12) - 10(-8)
      M) infusion at the same time as chorda stimulation caused no increase in salivary
      flow, but the salivary protein concentration was increased in a dose-dependent
      manner. In the sublingual gland, neither VIP nor the VIP antagonist affected
      chorda-evoked salivary flow and protein concentration. Thus, endogenous VIP may
      play a part in the regulation of both fluid and protein secretion, especially of
      protein, evoked by chorda stimulation at high frequency in the submandibular
      gland. These phenomena occurred only in the initial phase of secretion. In the
      sublingual gland, it seems likely that VIP plays no part in the regulatory
      mechanism, at least with regard to salivary fluid secretion in the acinar cells.

PMID- 9188991
TI  - Control of a trackball by the chin for communication applications, with and
      without neck movements.
AB  - The overall aim was to evaluate whether a trackball could be used for
      communication by people who cannot speak due to severe motor impairment. The
      precision of trackball control by isolated jaw movements or a combination of jaw
      and head movements was evaluated in 18 healthy physical-education students, free
      of overt symptoms of craniomandibular dysfunction. The participants were asked to
      operate a trackball using the chin to type a standard text of four short
      sentences. There were two experimental situations: nine participants performed
      the typewriting task with their heads fixed; the other nine performed this task
      with free head movements. Trackball operation moved to the cursor over an
      alphabetical keyboard displayed on a computer screen and character selection was
      made by depression of the left-hand click button using the chin. Participants
      were asked to perform the task as quickly and accurately as possible. Result
      showed that those with free head movement typed the test significantly faster
      than those restricted to using only their jaw muscles. The mean time per
      character selection was 2.4 s (SD 0.3) for the group with free head movement and
      2.7 s (SD 0.3) for the group using only jaw muscles. Group scores were not
      significantly different with regard to accuracy. It is suggested that a chin
      operated trackball could be used for communication applications both with and
      without neck movements.

PMID- 9188992
TI  - Comparative analysis of transforming growth factor-beta isoforms 1-3 in human and
      rabbit dentine matrices.
AB  - Previous studies have implicated transforming growth factor-beta (s)(TGF-beta) in
      both development. Here TGF-beta isoforms in dentine extracellular matrix were
      analysed because these molecules may participate in dental issue repair. EDTA
      soluble and collagenase-released fractions were isolated from human crown and
      root and rabbit incisor dentine samples and analysed for TGF-beta isoforms. TGF
      beta(1) was the major isoform detected in all samples and the only isoform
      detected in human dentine samples. TGF-beta(2) was detected only in the
      collagenase-released fraction of rabbit incisor dentine and was present at low
      levels. TGF-beta(3) was detected in both EDTA-soluble and collagenase-released
      fractions of rabbit dentine. Greater levels of the TGF-beta(1) isoform were
      detected in the rabbit than human dentine samples and some differences in
      distribution amongst the two tissue fractions were observed between these
      species. The presence of these isoforms of TGF-beta in dentine may provide a
      reservoir of growth factor in the matrix that could participate in processes
      leading to tissue repair after injury.

PMID- 9188993
TI  - Changes in the noradrenaline and acetylcholine content of three major salivary
      glands and in the salivation and protein component patterns of whole saliva in
      chronically isoprenaline-administered mice.
AB  - One group of mice was injected subcutaneously with 20 mg/kg body wt isoprenaline
      each day for 10 days; another group (control) was injected with saline. Half the
      animals of each group were kept untreated for a further 10 days for restoration.
      Chronic administration of isoprenaline caused enlargement of parotid (4-fold) and
      submandibular glands (1.7-fold) but had no effect on sublingual glands.
      Concomitantly, noradrenaline and acetylcholine contents were, in parallel,
      increased in parotid, decreased in sublingual, and unchanged in submandibular
      glands. Under these conditions, pilocarpine- or isoprenaline-induced salivation
      was not affected but phenylephrine-induced salivation was augmented; the protein
      component patterns of saliva characteristic of the three sialogogues were also
      changed. In addition, secretory proteins whose synthesis was induced by
      isoprenaline were found to be secreted by stimulation with different types of
      sialogogues. Most changes were reversible. These results indicate that continued
      beta-adrenoceptor stimulation not only causes broadly altered forms of saliva,
      probably by involving, in part, alpha-adrenoceptor hypersensitivity, but also
      changes the activities of both sympathetic and parasympathetic nerves to salivary
      glands in parallel, though the extent differs among the three glands.

PMID- 9188994
TI  - An amelogenin gene defect associated with human X-linked amelogenesis imperfecta.
AB  - Dental enamel is a product of ameloblast cells, which secrete a mineralizing
      organic matrix, composed primarily of amelogenin proteins. The amelogenins are
      thought to be crucial for development of normal, highly mineralized enamel. The X
      chromosomal amelogenin gene is a candidate gene for those cases of amelogenesis
      imperfecta, resulting in defective enamel, in which inheritance is X-linked. In
      this report, a kindred is described that has a C to A mutation resulting in a pro
      to thr change in exon 6 of the X-chromosomal amelogenin gene in three affected
      individuals, a change not found in unaffected members of the kindred. The proline
      that is changed by the mutation is conserved in amelogenin genes from all species
      examined to date.

PMID- 9188995
TI  - Correlation of microhardness and wear in differently eroded bovine dental enamel.
AB  - The purpose of the study was to compare the microhardness data of differently
      eroded enamel surfaces with the wear caused by toothbrushing. Sixty bovine enamel
      specimens were polished and prepared for microhardness determination. The
      polished surfaces were covered with tape except for a 1.3 x 10.0 mm window.
      Fifteen specimens each were stored in an erosive beverage (Sprite Light) for
      either 1, 5 or 15 min. Each specimen was immersed in 10 ml of the beverage. The
      remaining 15 specimens were not eroded. Interferometrical analysis revealed that
      substance loss after 15 min of erosion was negligibly low (about 75 mm). In all
      specimens Vickers microhardness determinations were conducted on eroded (= final
      hardness) and non-eroded (= initial hardness) enamel surfaces. The specimens were
      subsequently submitted to toothbrushing abrasion using a slurry consisting of 1 g
      non-fluoridated dentifrice in 5 ml artificial saliva. The total amount of tooth
      wear due to erosion and subsequent abrasion was profilometrically evaluated.
      Statistical analysis revealed a significant decrease in hardness and a
      significant increase in wear with increasing time of storage in the erosive
      beverage. Overall regression analysis yielded a statistically significant
      correlation between both initial and final hardness and the amount of tooth wear.
      The correlation of abrasion and final hardness could be described by a quadratic
      mathematical function. It is concluded that the susceptibility of eroded enamel
      to toothbrushing abrasion can be correlated with Vickers microhardness values,
      thereby suggesting an overproportionate increase of abrasion with decreasing
      hardness values.

PMID- 9188996
TI  - Development of a recording system for saliva pH with and complete denture by
      telemetry.
AB  - A new system for measuring saliva pH by radio telemetry was developed. The system
      was built into a lower complete denture and could operate for about 19 h. The
      maximum error in the range pH 5-8 was 0.15 pH, and the correlation when values
      were compared with those from a glass-electrode pH meter was 0.99. That this
      system operates successfully was confirmed in a clinical experiment.

PMID- 9188997
TI  - Intranasal administration of midazolam: pharmacokinetic and pharmacodynamic
      properties and sedative potential.
AB  - This study investigated the pharmacodynamic effects and sedative potential of
      midazolam administered by the intranasal route to adult volunteers. A double
      blind, randomized, controlled study was carried out on seventeen healthy, male
      volunteers to study plasma level changes, sedative effects and variations in
      vital signs following intranasal administration of 0.2 mg/kg and 0.3 mg/kg doses
      of midazolam. Eight subjects received 0.2 mg/kg midazolam, seven received 0.3
      mg/kg. Each subject rested for 15-20 minutes after placement of vital sign
      monitors and venipuncture needles before administration of midazolam. Behavior
      during the rest period was designated as the control so that each subject acted
      as his own control. Each subject's behavior was assessed on a scale of 1 (asleep)
      to 8 (excited). Plasma concentrations of midazolam were analyzed using venous
      blood samples from each of three randomly selected subjects for each of the two
      doses. Vital signs, monitored continuously, included electrocardiogram, heart
      rate, blood pressure, respiratory rate and oxygen saturation (SPO2). Plasma
      concentration of midazolam in both groups maintained adequate sedation levels
      with each group sustaining favorable sedation conditions from 15-20 minutes to 55
      60 minutes. Individual variations of midazolam plasma concentration within the
      0.3 mg/kg group were greater than those of the 0.2 mg/kg group. Normal vital sign
      variations due to the nasal instillation of midazolam were observed in both
      groups. Some minor respiratory depression was observed in the 0.2 mg/kg group.
      One instance of severe respiratory depression was observed in the higher dose
      group. Although both doses of midazolam were effective, no benefit was observed
      using a dose of 0.3 mg/kg. Indeed, a 0.3 mg/kg intranasal dose of midazolam may
      actually produce severe respiratory depression.

PMID- 9188998
TI  - The ethological method as a means for evaluating stress in children two to three
      years of age during a dental examination.
AB  - A dental examination could be perceived by small children as an "at-risk"
      situation. The behaviors observed in these children during a dental examination
      depend not only on the examination situation but also on other factors, such as
      the sex of the child or the sex of the accompanying parent. The ethological
      method provided a means for evaluating behavioral differences due to the sex of
      the child and that of the accompanying parent. Results showed that girls appeared
      better able to master the examination situation than did boys, regardless of the
      sex of the accompanying parent. The girls appeared more secure, and exhibited
      more exploratory behavior than did the boys. The boys, on the other hand,
      appeared less secure than did the girls especially when the father was the
      accompanying parent.

PMID- 9188999
TI  - Streptococcus mutans in children using nursing bottles.
AB  - This study aimed at comparing S.mutans in pairs of children within families; both
      children used a sweetened nursing bottle beyond the dietary need, while one child
      was affected with nursing bottle caries (NBC), the other not. Seven families were
      selected. The children of a pair showed no dissimilarities as regards dietary
      habits. Mean patient-age was 3.7 yrs, controls 5.7 yrs. Saliva and plaque were
      sampled for CFU-counting and clonal (DNA) type-screening of S.mutans. The NBC
      patients harbored significantly more S.mutans than the controls (mean 5.8 CFU/ml
      vs. 2.9 CFU/ml). While the controls were colonized with 2-5 clonal types of
      S.mutans, in the patients only one type was observed. The results were not
      consistent for NBC-risk assessment by CFU-counting. An inverse relationship
      between the number of clonal S.mutans types and NBC is suggested.

PMID- 9189000
TI  - Feeding practices and dental caries in an urban Canadian population of Vietnamese
      preschool children.
AB  - The aim of this project was to determine the severity of nursing caries, and to
      examine contributing behavioral factors, in a group of Vietnamese families in
      British Columbia, Canada. The data collected became the basis for a community
      based oral health promotion program. Information on feeding, dental health
      practices, and dental caries were collected for 60 mother/child pairs. For
      children > or = 18 mos, prevalence of nursing caries was 64 percent. Sixty-five
      percent of all children had a naptime bottle, and 85 percent > or = 18 mos had a
      "comfort" bottle that was carried around, and drunk from during the day. Milk was
      the most common beverage. A "comfort" bottle was significantly related to the
      presence of nursing caries, P = 0.02; a naptime bottle had a less significant
      association, P = 0.07. Dental knowledge questions revealed that all mothers knew
      that a child who had a "comfort" bottle could get tooth decay, but 63 percent
      thought that cavities were not a problem in baby teeth.

PMID- 9189001
TI  - Microscopic studies of accessory canals in primary molar furcations.
AB  - The purpose of this study was to evaluate the incidence of accessory canals in
      the furcation region of human primary second molars. Forty freshly extracted
      teeth were radectomized and furcations were separated. The severed pulp chamber
      floors were decalcified and dehydrated. Paraffin embedding followed and cross-cut
      serial sections were taken from the specimens. Microscopic examination of each
      section followed. Sixteen out of twenty (80 percent) of the maxillary and fifteen
      out of twenty (75 percent) of the mandibular primary second molars demonstrated
      accessory foramina in the furcation area. 17.3 percent of the accessory foramina
      were found in the pulp chamber floor and 82. 7 percent were observed
      interradicular, close to the periodontal ligament. Thirty percent of the primary
      second molars demonstrated accessory canals, running from the pulp chamber to the
      periodontal ligament. Within the limitations of a microscopic investigation it is
      assumed that accessory furcation canals might be responsible for interradicular
      bone pathology in case of pulpal inflammation or necrosis.

PMID- 9189002
TI  - How does the use of different sugar products predict caries in 18-year-old Finns?
AB  - The aim of this study was to determine whether self-reported (but diagnosed
      previously by a dentist) caries incidence of eighteen-year-olds could be
      predicted based on their use of sweets, cakes sugar-sweetened coffee or tea
      between the ages of twelve and eighteen. The data were collected as part of the
      nationwide research program, the Adolescent Health and Lifestyle Survey. All
      Finns born in 1968 and having their birthdays on 20-25th July formed the same (N
      = 1106). The 1981 survey (adolescents at the age of twelve) was the baseline, and
      follow-up questionnaires were sent in 1983, 1985 and 1987. The chi-square test
      and logistic regression model were used in the analyses. Different sugar products
      were slightly more significant predictors with the chi-square test than by
      logistic regression model. Among boys, the most common predictor, daily use of
      sugar-sweetened coffee, was an important predictor, although the risk was quite
      low. For girls, no predictors were found.

PMID- 9189003
TI  - An in vitro caries inhibition of photopolymerized glass ionomer liners.
AB  - Caries inhibition of traditional chemical cure glass ionomers has been
      established. The newer photopolymerized glass ionomers demonstrate a different
      composition that may impair the ability of providing prevention to secondary
      caries at restoration margins. The purpose of this study was to evaluate the
      caries inhibition of photopolymerized glass ionomers (Vitrebond-3M Dental
      Products, Photac Bond-ESPE/Premier Dental Products) compared to a
      photopolymerized composite resin (Pertac Universal Bond-ESPE/Premier) control.
      Two standardized Class V preparations were placed in thirty permanent molars, the
      gingival margin placed below the cementoenamel junction. Equal numbers of
      preparations were restored with Vitrebond, Photac Bond and Pertac Universal Bond,
      according to manufacturer's instructions. The teeth were coated with an acid
      resistant varnish to within 2 mm of the restoration margins. All teeth were
      subjected to an artificial caries challenge (pH 4.2) for five days, then axial
      sections of 100 microns were cut longitudinally through the restored margins and
      photographed under polarized light microscopy. The polarized micrographs were
      projected onto a digitizing pad, where demineralized areas adjacent to the
      restoration margins were quantitated. Results demonstrated the mean (+/- S.D.)
      area (microns2) demineralization 100 microns from the restoration gingival margin
      to be: Photac Bond 66.1 +/- 27.8; Vitrebond 47.2 +/- 37.2; Pertac Universal Bond
      120.9 +/- 66.0. Duncan's multiple range test indicated there was no statistically
      significant difference in demineralization inhibition between the two
      photopolymerized glass ionomers Photac Bond and Vitrebond (p < 0.05), but both
      photopolymerized glass ionomers demonstrated significantly less demineralization
      than the Pertac Universal Bond composite resin control (p < 0.05).

PMID- 9189004
TI  - Resin-modified glass ionomer cements (RM GICs) implications for use in pediatric
      dentistry.
AB  - The changing face of restorative dentistry has resulted in the introduction of
      numerous materials. The emphasis on durability, strength, and esthetics led to
      the introduction of glass ionomer based formulations. The latest entrants into
      this arena are the resin-based glass ionomer cements. The combined properties of
      enhanced strength and fluoride release make this material an attractive choice
      for most restorative procedures. For the pediatric dentist, this material has
      special value due to its preventive characteristics, ease of placement and
      esthetics. The amalgam controversy has led practitioners and patients to opt for
      non-amalgam based restorations. The introduction of "compomers" provides an
      exciting alternative to amalgam. The purpose of this article is to highlight the
      properties of these "new age" materials and present a case report on the use of
      one such commercially available resin/ionomer cement.

PMID- 9189005
TI  - Changing welfare as we know it: some thoughts about the impact on children.
AB  - The new federal welfare legislation eliminates an entitlement to benefits or
      services for different groups of recipients. A review is provided of some of the
      legislative provisions and their consequences, with particular concern for the
      impact on children. The availability and use of child care arrangements for
      working parents illustrates the complexity of "transforming welfare as we know
      it."

PMID- 9189006
TI  - Mid-1990s review of Medicaid and Medicaid dentistry.
AB  - In light of a federal report on the extremely limited availability of preventive
      dental services for children under the Medicaid program, a review is provided of
      the evolving comparative share of general health expenditures and Medicaid funds
      that are spent on dental services. The findings indicate that during the 1990s,
      dentistry in general and within the Medicaid program occupies a continuing
      decreasing share of expenditures.

PMID- 9189007
TI  - Analysis of antibody-dependent cell-mediated cytotoxicity in autoimmune thyroid
      disease.
AB  - There is no consensus on the role of antibody-dependent cell-mediated
      cytotoxicity (ADCC) in autoimmune thyroid disease; recent reports have suggested
      that antibodies mediating ADCC are found particularly in patients with primary
      myxoedema, occur less frequently in Hashimoto's thyroiditis and are absent in
      Graves' disease. Using an ADCC assay with a single source of effector and target
      cells, and expressing results as lytic units, we have found antibodies capable of
      mediating ADCC in 9 of 17 patients with primary myxoedema, 9 of 22 patients with
      Hashimoto's thyroiditis and 6 of 22 patients with Graves' disease. There was no
      significant difference between the groups in this distribution. Mean levels of
      ADCC activity were not significantly different comparing primary myxoedema and
      Hashimoto's thyroiditis patients, although levels were lower in Graves' disease
      patients compared to those with Hashimoto's thyroiditis (P < 0.05). There was no
      correlation between TPO antibodies (total IgG or IgG subclasses) measured by
      ELISA and ADCC activity. These results suggest that thyroid antigens besides TPO
      are involved in ADCC and that antibodies mediating ADCC are not restricted to
      subgroups of patients with autoimmune thyroid disease.

PMID- 9189009
TI  - Probing for cerebrospinal fluid antibody specificities by a panel of random
      peptide libraries.
AB  - In a state of health the central nervous system is nearly devoid of macrophages,
      T and B cells. However, such cells are required to initiate the inflammation
      associated with multiple sclerosis (MS). An important issue in understanding the
      pathogenesis of such conditions is to fully define the T and B cell
      specificities. Using random peptide libraries, we have analysed the cerebrospinal
      fluid antibody specificities within one oligoclonal "band" from a patient with
      MS. The selected peptides from a 6-mer library revealed two peptide motifs S
      (S/T/Q) (R/S) (N/G) FP and PRn (G/P) FF. Interestingly, the first motif was also
      selected from a 15-mer library, while the second motif was selected from the 9
      mer library. In addition, distinct but structurally related peptides to the
      mentioned motifs were also selected. Surprisingly, a SwissProt search with these
      motifs revealed a significant linear homology with collagen proteins, the 68 kDa
      neurofilament protein, versican and other proteins from viruses such as herpes
      simplex virus, human cytomegalovirus and human papillomavirus. Thus, the
      observation that antibodies present within one oligoclonal immunoglobulin band
      would recognize peptides, some that might be related by only the structure,
      raises the question of the involvement of multiple pathogens in MS.

PMID- 9189008
TI  - Insight into screening immunoglobulin gene combinatorial libraries in a phage
      display vector: a tale of two antibodies.
AB  - Combinatorial libraries of immunoglobulin genes in "phage display" vectors are a
      powerful tool for obtaining antigen-specific antibody fragments. To date, this
      approach has been used to isolate abundant, but not rare, human autoantibodies of
      IgG class. We have compared the relative efficiencies of panning pComb3 libraries
      made from intrathyroidal plasma cells for abundant human autoantibodies to
      thyroid peroxidase (TPO) and rare autoantibodies to the thyrotropin receptor
      (TSHR). TPO-specific Fab were readily obtained from a library using three
      different forms of recombinant antigen, (i) purified TPO, (ii) impure TPO in
      culture medium and, (iii) TPO expressed on the surface of CHO cells. In contrast,
      TSHR-specific Fab were not isolated. This was the case despite repeated pannings
      of six libraries from three optimal patients (IgG/kappa and IgG/lambda libraries
      for each patient). Both purified recombinant TSHR and CHO cells expressing TSHR
      on their surface were used. Library enrichment was observed on some screenings.
      However, Fab expressed by individual clones or from enriched libraries were not
      specific as determined by (i) binding to purified, radio-labeled antigen, (ii)
      FACS analysis of TSHR on intact CHO cells and, (iii) inhibition of radiolabeled
      TSH binding. Remarkably, in screening for both TPO- and TSHR-specific Fab,
      neither library enrichment nor the retention of cDNA inserts of the correct size
      correlated with obtaining Fab with the antigenic specificity sought. Indeed,
      excellent enrichment could be observed with conditioned medium from untransfected
      cells. Our data suggest that the key to isolating rare antibodies from phage
      display libraries is not the creation of vast libraries of greater diversity or
      even the development of more stable vectors. Rather, success in this endeavor
      appears to require reducing the "noise" of non-specific clones in a moderately
      sized library.

PMID- 9189010
TI  - High circulating IL-6 level in Graves' ophthalmopathy.
AB  - IL-6 is a paracrine and autocrine cytokine, which acts in the regulation of
      immunological and inflammatory processes. Its production can be observed in
      different cell types, as well as thyrocytes. The purpose of the study was to
      examine the serum IL-6 levels between the patients with Graves' disease (N = 47)
      and without (N = 29) ophthalmopathy in respect of the presence of inflammatory
      eye signs and thyroiditis, thyroid function and radioiodine or medical
      treatments. The serum IL-6 levels were greater (P < 0.025) in the patients with
      ophthalmopathy (440 +/- 32.4 pg/ml) than in those without eye disease (81.6 +/-
      25.2 pg/ml). An elevated serum IL-6 levels could be detected in 22 out of 47
      patients with ophthalmopathy with longer manifestation of thyroid disease than
      one year in comparison with those who had shorter (694 +/- 35.3 pg/ml vs 215.8 +/
      27.9 pg/ml, P < 0.05). The increase showed a strong association with the
      inflammatory signs of eye disease in the patients with Graves' hyperthyroidism
      compared with those without ophthalmopathy (513.3 +/- 33.7 pg/ml vs 96.9 +/- 12.1
      pg/ml, P < 0.025). Euthyroid function and the presence of thyroiditis did not
      influence the serum IL-6 levels. Radioiodine and medical treatments did not lead
      to a remarkable decrease in the serum IL-6 levels. The results supported that IL
      6 cytokine may be an important factor in the inflammatory events of Graves'
      ophthalmopathy.

PMID- 9189011
TI  - Mononuclear cytotoxicity and proliferation towards glucose stimulated rodent
      pancreatic islet cells.
AB  - Diabetes is due to an autoimmune cellular immunologic destruction of the
      pancreatic beta cells. By the use of a chromium release assay and a proliferation
      assay we have investigated the possible role of beta cell activity for this
      destruction. Results show that in vitro glucose stimulated pancreatic islet cells
      are subjects to a slight but significantly higher cellular immunologic
      destruction by mononuclear spleen cells than unstimulated islet cells. The
      functional dependency of the islet cell destruction must be a product of both a
      mononuclear cell dysfunction and a specific islet cell pattern. This is due to
      the fact that all combinations of mononuclear cells and islet cells from diabetes
      prone BB rats and non-diabetes prone WF rats tested against each other, results
      in functional dependent cytotoxicity, except for the assay in which both effector
      cells and target cells are of WF rat origin. Additional observations indicate,
      that the diabetes prone BB rat mononuclear cells need previous in vivo activation
      as only cells from diabetic individuals, and not normoglycemic ones, display the
      reaction in question. Functional dependent cytotoxicity is validated in an other
      IDDM animal model--the NOD mouse. NOD mononuclear cells towards the murine MIN-6
      beta cell line results in increased cellular cytotoxicity when the latter is
      glucose stimulated. Also the proliferative response of BB rat mononuclear cells
      to whole islets tend to show function dependency.

PMID- 9189012
TI  - Polymorphism of the human immunoglobulin heavy chain locus in rheumatoid
      arthritis.
AB  - The genetic origin of Rheumatoid Arthritis (RA) is largely unknown. The purpose
      of this investigation was to assess the potential genetically determined
      involvement of the immunoglobulin (Ig) heavy chain variable region (VH) locus in
      the pathogenesis of RA. We tested the hypothesis of whether there is a genetic
      linkage between a structural abnormality of the VH gene complex and autoantibody
      hyperproduction in RA. We used restriction endonuclease generated polymorphism
      with human VH gene-family-specific probes to examine genomic DNA from a RA family
      and from unrelated RA patients from both the Tunisian and the European
      populations. The use of DNA samples from these ethnic origins permitted a further
      evaluation of the polymorphism of the human VH locus. While we found that the
      polymorphism of the VH locus was lower in the Tunisian population, we could not
      detect a restriction site polymorphism pattern restricted to RA. Together, our
      results do not support the involvement of major abnormalities of the Ig VH locus
      as a primary source in the development of RA.

PMID- 9189014
TI  - Amazed and dismayed.

PMID- 9189013
TI  - Some anti-thyroperoxidase antibodies positive sera give a pANCA pattern on
      ethanol-fixed human neutrophils: cross-reactivity or false positives?
AB  - Fifty-six sera from patients with autoimmune thyroiditis and 33 sera from
      patients with MPO-ANCA were examined in order to ascertain whether a cross
      reactivity between MPO-ANCA and anti-thyroperoxidase (aTPO) was present. Sera
      from 20 healthy donors aTPO and aMPO negative were used as control. About 95% of
      heat inactivated sera from patients with autoimmune thyroiditis and from controls
      gave positive results (atypical pANCA pattern) on ethanol-fixed neutrophils. The
      prevalence of positive results was significantly lower when unheated aTPO
      positive sera were used (17.8%). On the other hand, only 9% of sera with MPO-ANCA
      were positive on cryostatic sections of human thyroid. Indirect
      immunofluorescence tests (IF) on human neutrophils with MPO defect were negative
      with sera from patients with MPO-ANCA, but uninactivated sera with aTPO and
      positive for pANCA on normal neutrophils showed a very high prevalence of
      positive results (90%). According to our data only few sera positive for aTPO
      recognize "normal" MPO, but the majority of sera from patients with autoimmune
      thyroiditis and positive for pANCA on normal neutrophils recognize also an
      "abnormal" MPO. On the other hand MPO-ANCA usually recognize epitopes presently
      only on the normal enzyme, a small proportion of these autoantibodies can react
      with TPO. Heat inactivated sera give false positive results for pANCA on ethanol
      fixed human neutrophils.

PMID- 9189016
TI  - Finance ... predictions of big cost increases in health care over the next five
      years.

PMID- 9189015
TI  - Don't bring us down.

PMID- 9189017
TI  - Technology. Upping the odds of survival.

PMID- 9189018
TI  - Long-term care ... average purchase prices of nursing homes and retirement
      facilities.

PMID- 9189019
TI  - Managed care. Well, excuuuse us!

PMID- 9189020
TI  - Budget balance.

PMID- 9189021
TI  - Disease management ... drug data debate.
AB  - Desperately seeking a new way to generate profits, pharmacy benefit managers are
      trying to sell employers and HMOs on the notion of using their mountains of drug
      claim information to manage chronic diseases. But skeptics point out that
      prescription data tell only part of the treatment story.

PMID- 9189022
TI  - Bye-bye big boards. Bogged down by too many trustees, health systems streamline
      to set clearer goals and speed up decisions.
AB  - As health systems grow, the number of trustees and governing boards often must
      shrink to cut back on red tape and budget bottlenecks. Hospital management also
      typically needs restructuring, with fewer CEOs and more regional managers taking
      care of business.

PMID- 9189023
TI  - Image problems. Science, fear and the politics of mammograms.
AB  - When it comes to breast cancer screening, science takes a backseat to the
      politics of fear. In fact, researchers can't even decide whether to recommend
      routine screenings for women in their 40s.

PMID- 9189024
TI  - Physicians. Going to court for clout.

PMID- 9189025
TI  - Construction. High and dry.

PMID- 9189026
TI  - Medicaid payments. Has Boren worn out its welcome?

PMID- 9189027
TI  - Home health. It's an outside job.

PMID- 9189028
TI  - HospitalPulse ... January 1997.

PMID- 9189029
TI  - Cerebral amyloid angiopathy and apolipoprotein E: bad news for the good allele?

PMID- 9189030
TI  - Paraneoplastic primary lateral sclerosis and amyotrophic lateral sclerosis.

PMID- 9189031
TI  - Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus
      conference. Conference Participants.
AB  - We held an international consensus conference on frontotemporal dementia,
      behavioral disturbances, and parkinsonism linked to chromosome 17 to determine
      whether these are homogeneous or heterogeneous disorders, to agree on
      terminology, and to develop strategies for further research. The group identified
      13 kindreds with sufficient evidence for linkage, finding in common to all a
      critical 2 cM between markers D17S791 and D17S800. There was agreement that (1)
      despite previous descriptions that have emphasized one or another clinical or
      neuropathological feature, the kindreds share clinical and neuropathological
      features; (2) until more specific information about the genetic defects becomes
      available, this disorder is best termed frontotemporal dementia and parkinsonism
      linked to chromosome 17; and (3) further research will be enhanced by identifying
      the gene or genes responsible for this disorder, detecting additional cases
      within known families and, in new families, correlating mutations with phenotypes
      and more fully delineating the clinical, neuropsychological, and
      neuropathological characteristics of this disorder.

PMID- 9189032
TI  - High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral
      amyloid angiopathy.
AB  - From the somewhat conflicting published data on apolipoprotein E (apoE) genotype
      in hemorrhage due to cerebral amyloid angiopathy (CAA), it is unclear whether
      apoE genotype influences the risk of CAA-related hemorrhage independently of its
      association with concomitant Alzheimer's disease (AD). We determined the apoE
      genotypes of 36 patients presenting with cerebral hemorrhage associated with
      histologically confirmed CAA. The frequency of apoE epsilon 2 was 0.25 and the
      frequency of apoE epsilon 4 was 0.18. Patients with CAA-related hemorrhage and
      concomitant AD pathology (CERAD criteria, n = 17) had a high apoE epsilon 4
      frequency, close to that in AD cases without hemorrhage. Patients in whom CAA
      related hemorrhage occurred in the absence of significant AD pathology (n = 13)
      had an apoE epsilon 4 frequency somewhat lower than non-AD controls without
      hemorrhage. However, in CAA-related hemorrhage, the apoE epsilon 2 frequency was
      high regardless of whether significant AD pathology was present. We conclude that
      whereas possession of apoE epsilon 2 may be a risk factor for cerebral hemorrhage
      due to CAA, apoE epsilon 4 is a risk factor for concomitant AD but not an
      independent risk factor for CAA-related hemorrhage.

PMID- 9189033
TI  - Motor neuron syndromes in cancer patients.
AB  - Previous reports indicate that motor neuron disease (MND) may rarely be
      associated with systemic cancer. We have encountered 14 patients with MND and
      cancer who formed three distinct groups. Group 1: Three patients developed a
      rapidly progressive MND, less prominent symptoms of involvement of other areas of
      the nervous system, and anti-Hu antibodies. Group 2: Five women developed signs
      of upper motor neuron (UMN) disease, initially resembling primary lateral
      sclerosis (PLS), and breast cancer. In 4, symptoms of UMN occurred within 3
      months of cancer diagnosis or tumor recurrence. They had no metastases or spinal
      cord compression. Serum anti-neuronal antibodies were negative. Three patients
      are alive (follow-up of 156, 15, and 12 months), and 2 remain without lower motor
      neuron signs. Group 3: Six patients developed MND resembling amyotrophic lateral
      sclerosis between 47 months before and 48 months after their cancer diagnosis. In
      group 1, the MND associated with the anti-Hu antibody is unequivocally
      paraneoplastic. In group 2, the proximate onset of MND with the diagnosis of
      cancer or its recurrence, its pure or long-lasting UMN signs, and its association
      with breast cancer, suggest that the disorder may be paraneoplastic. Although for
      most cancer patients who develop MND the occurrence of both disorders is probably
      coincidental, in some patients with MND a careful search for an underlying cancer
      is warranted (ie, patients in groups 1 and 2).

PMID- 9189034
TI  - Altered intrathymic T-cell repertoire in human myasthenia gravis.
AB  - In myasthenia gravis, the thymus is thought to be the primary site of
      autosensitization. We investigated the V beta T-cell repertoire at different
      intrathymic differentiation stages in 17 patients with myasthenia gravis and 8
      age-matched control subjects by tricolor immunofluorescence, using a panel of six
      anti-V beta antibodies. We observed an increased expression of V beta 5.1 and V
      beta 8 subfamilies in the patients compared to the control subjects. These
      increases were observed not only in mature cells but also in the latest thymic
      precursors of mature cells (double-positive CD3 high), while there was no change
      in intermediate precursors (double-positive CD3 low), pointing to biased
      selection during intrathymic differentiation. In addition, there was a strong
      correlation between the percentage of V beta 5.1+ and V beta 8+ cells among both
      the CD4 and CD8 subsets in the patients, but not in control subjects, suggesting
      that thymic events relevant to the disease lead to these selected populations.
      Finally, location studies of V beta 5.1+ cells on thymic sections indicated that
      these cells were overrepresented both in the core of germinal centers and in
      perifollicular areas of hyperplastic thymuses, suggesting a role in the
      autoimmune response. Taken together, these findings are compatible with the
      hypothesis of a biased intrathymic selection in myasthenia gravis.

PMID- 9189036
TI  - Magnetic resonance imaging of periventricular leukomalacia and its clinical
      correlation in children.
AB  - The prevalence of periventricular leukomalacia and its association with clinical
      neurological signs in school-age preterm children are unknown. We matched 42
      eight-year-old children who were born before term with birth weights lower than
      1,750 gm (mean, 1,410 gm; gestational age, 31 weeks) with 42 children who were
      born at term and of normal birth weight, to compare clinical neurological status
      and magnetic resonance imaging findings. Of the children born prematurely, 9.5%
      had cerebral palsy and 31% had minor neurological dysfunction whereas 9% of the
      children born at term had minor neurological dysfunction and none had cerebral
      palsy. Deviations in tongue movements, heel walking. Fogs test results, and
      finger opposition, as well as behavioral disturbances, differentiated the preterm
      from the full-teem group. The prevalence of periventricular leukomalacia among
      all children born prematurely was 32%. It was observed in all children with
      cerebral palsy, in 25% with minor neurological dysfunction, and in 25% of the
      clinically healthy preterm children. None of the children born at term had
      evidence of periventricular leukomalacia. Children with periventricular
      leukomalacia especially demonstrated poor performance on heel walking and Fogs
      test. Though commonly found in preterm children, periventricular leukomalacia is
      not uniformly associated with abnormal neurological findings. A thorough
      neurological examination is a better predictor of later developmental problems
      than is magnetic resonance imaging.

PMID- 9189035
TI  - Presenilin-1 protein expression in familial and sporadic Alzheimer's disease.
AB  - Mutations of the presenilin PS1 and PS2 genes are closely linked to aggressive
      forms of early-onset (< 60 years) familial Alzheimer's disease. A highly specific
      monoclonal antibody was developed to identify and characterize the native PS1
      protein. Western blot analyses revealed a predominant 32-kd immunoreactive
      polypeptide in a variety of samples, including PC12 cells transfected with human
      PS1 complementary DNA, brain biopsy specimens from demented patients, and
      postmortem samples of frontal neocortex from early-onset familial Alzheimer's
      disease cases (PS1 and PS2), late-onset sporadic Alzheimer's disease cases, and
      cases of other degenerative disorders. This truncated polypeptide contains the N
      terminus of PS1 and appeared unchanged across cases. In 2 early-onset cases
      linked to missense mutations in the PS1 gene, a PS1 immunoreactive protein
      (approximately 49 kd) accumulated in the frontal cortex. This protein was similar
      in size to full-length PS1 protein present in transfected cells overexpressing
      PS1 complementary DNA, and in lymphocytes from an affected individual with a
      deletion of exon 9 of the PS1 gene, suggesting that mutations of the PS1 gene
      peturb the endoproteolytic processing of the protein. Immunohistochemical studies
      of control brains revealed that PS1 is expressed primarily in neurons, with the
      protein localized in the soma and dendritic processes. In contrast, PS1 showed
      striking localization to the neuropathology in early-onset familial Alzheimer's
      disease and sporadic Alzheimers' disease cases. PS1 immunoreactivity was present
      in the neuritic component of senile plaques as well as in neurofibrillary
      tangles. Localization of PS1 immunoreactivity in familial and sporadic
      Alzheimer's disease suggests that genetically heterogeneous forms of the disease
      share a common pathophysiology involving PS1 protein.

PMID- 9189037
TI  - Painful proximal diabetic neuropathy: inflammatory nerve lesions and spontaneous
      favorable outcome.
AB  - Proximal diabetic neuropathy is a disabling neuropathy that occurs predominantly
      in non-insulin-dependent diabetic patients over the age of 50. Inflammatory
      lesions have been found in nerve biopsy specimens of diabetic patients with
      severe proximal neuropathy or with other patterns of multifocal neuropathy. Some
      of these patients respond dramatically to treatment with corticosteroids or with
      other immunomodulators. In this article we report on our findings in 4 additional
      patients with painful proximal diabetic neuropathy and different patterns of
      inflammatory nerve lesions whose condition improved spontaneously shortly after
      performance of a nerve biopsy, without additional treatment.

PMID- 9189038
TI  - A new type of hereditary motor and sensory neuropathy linked to chromosome 3.
AB  - We report the clinical, pathological, and genetic findings of 23 patients in 8
      families with hereditary motor and sensory neuropathy (proximal dominant form)
      (HMSN-P) in Okinawa, Japan. The clinical features were unique with respect to
      autosomal dominant inheritance, Kennedy-Alter-Sung syndrome-like proximal
      dominant neurogenic atrophy, obvious sensory involvement, painful muscle cramp,
      fasciculations, areflexia, and high incidences of elevated creatine kinase
      levels, hyperlipidemia, and diabetes mellitus. Electrophysiological and
      pathological studies revealed typical motor and sensory axonal neuropathy, and
      decreased numbers of anterior born and dorsal ganglion cells, which suggested the
      presence of neuronopathy in HMSN-P. Genetic linkage studies showed a lod score of
      4.04 (two-point analysis) in DNA marker D3S1284. Haplotype analysis showed that
      the gene locus of the disease was mapped to 3p14.1-q13 bracketed by D3S1285 and
      D3S1281. In this region, the patients' chromosomes showed an obvious increase in
      the allele frequency of five markers. One allele in D3S1591 was identical in all
      patients but had a low frequency in the control population. This finding
      suggested the presence of linkage disequilibrium and a common origin of this
      allele in all patients with HMSN-P. The HMSN-P described here is a new clinical
      entity characterized by unique clinical manifestations and a new gene locus.

PMID- 9189039
TI  - A mismatch between kinesthetic and visual perception in Parkinson's disease.
AB  - Kinesthesia may be defective in patients with Parkinson's disease (PD), and this
      defect conceivably has a role in parkinsonian hypokinetic symptoms. In the
      present study, PD patients used kinesthetic perception to estimate the amplitude
      of passive angular displacements of the index finger about the
      metacarpophalangeal joint and to scale them as a percentage of a reference
      stimulus. The reference stimulus was either a standard kinesthetic stimulus
      preceding each test stimulus (task K) or a visual representation of the standard
      kinesthetic stimulus (task V). In task V, the PD patients' underestimation of the
      amplitudes of finger perturbations was significantly greater than that of normal
      subjects, but not for task K. PD patients' underestimation was also greater in
      task V than in task K; the difference between the underestimations was
      significantly greater than for normal subjects. These results suggest that, when
      kinesthesia is used to match a visual target, distances are perceived to be
      shorter by the PD patients. Assuming that visual perception is normal,
      kinesthesia is "reduced" in PD patients. This reduced kinesthesia, when combined
      with the well-known reduced motor output and probably reduced corollary
      discharges, implies that the sensorimotor apparatus is "set" smaller in PD
      patients than in normal subjects.

PMID- 9189040
TI  - Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in
      myasthenia gravis. Myasthenia Gravis Clinical Study Group.
AB  - We have conducted a trial to randomly assess the efficacy and tolerance of
      intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis
      (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with
      MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n
      = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The
      main end point was the variation of a myasthenic muscular score (MSS) between
      randomization and day 15. The MSS variation was similar in both groups (median
      value, +18 in the PE group and +15.5 in the i.v.Ig group, p = 0.65). Similar
      efficacy, although slightly reduced in the 5-day group was observed with both
      i.v.Ig schedules. The tolerance of i.v.Ig was better than that of PE with a total
      of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the i.v.Ig
      group (p = 0.01). Although our trial failed to show a pronounced difference in
      the efficacy of both treatments, it exhibited a very limited risk for i.v.Ig.
      i.v.Ig is an alternative for the treatment of myasthenic crisis. The small sample
      sizes in our trial, however, could explain why a difference in efficacy was not
      observed. Further studies are needed to compare PE with i.v.Ig and to determine
      the optimal dosage of i.v.Ig.

PMID- 9189042
TI  - Human T-cell lymphotropic virus type I-associated facial nerve palsy in Trinidad
      and Tobago.
AB  - To assess the association of the human T-cell lymphotropic virus type I (HTLV-I)
      and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78
      patients consecutively admitted to the Port of Spain General Hospital in
      Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve
      palsy. Patients were compared with two control groups: a population-based group
      of persons 20 years and older and a hospital-based group of patients 15 to 84
      years old admitted to the medical wards. Sixty-two patients were Trinidadians of
      African origin and 16 were Trinidadians of East Indian origin. None of the East
      Indian patients was HTLV-I antibody positive. Three Afro-Trinidadians were
      infected with human immunodeficiency virus type 1 and 1 was coinfected with this
      virus and HTLV-I. Of the remaining 58 Afro-Trinidadians, 12 (20.7%) were HTLV-I
      positive only. This rate was statistically higher than the HTLV-I seroprevalence
      in the Afro-Trinidadian general population (3.5%) and the hospital control group
      (5.6%). After age standardization, the HTLV-I prevalence for patients with facial
      nerve palsy remained significantly elevated. HTLV-I antibody assays should be
      performed on all patients with idiopathic facial nerve palsy of the lower motor
      neuron type who live in HTLV-I endemic areas or are migrants from these areas.

PMID- 9189041
TI  - Multiple sclerosis: re-expression of a developmental gene in chronic lesions
      correlates with remyelination.
AB  - Central nervous system tissue from multiple sclerosis and non-multiple sclerosis
      subjects was studied for the expression of exon 2 myelin basic protein gene
      products at the protein and message levels by immunocytochemistry and in situ
      hybridization, respectively. The exon 2-encoded protein sequence is normally
      expressed during development (myelination) within the 21.5- and 20.2-kd isoforms
      of myelin basic protein and is downregulated in the adult central nervous system
      where the 18.5- and 17.2-kd isoforms predominate, the latter devoid of exon 2
      owing to alternative splicing. Exon 2 myelin basic protein gene products were
      readily demonstrable in multiple sclerosis samples, the highest levels
      correlating with remyelination in chronic lesions while normal adult central
      nervous system and non-multiple sclerosis material showed very low levels and
      fetal human central nervous system tissue (a positive control) showed high
      levels. We conclude that recapitulation of ontogenetic events during myelin
      repair accounts for the increased expression of the exon 2-encoded protein
      sequence in the adult central nervous system during multiple sclerosis, an event
      that might underly the previously observed T-cell activation to this protein
      sequence during relapses.

PMID- 9189043
TI  - A novel presenilin-1 mutation: increased beta-amyloid and neurofibrillary
      changes.
AB  - The prevalence of known mutations in presenilin genes (PS1 and PS2) causing early
      onset familial Alzheimer's disease (FAD) was assessed in a population of 98
      singleton early-onset AD cases, 29 early-onset FAD cases, and 15 late-onset FAD
      cases. None of the cases tested positive for the eight mutations initially
      reported, and none of these mutations were observed in 60 age-matched controls. A
      novel mutation (R269H) in PS1 was found in a single case of early-onset AD but
      not in any other AD or control case. Thus, the PS mutations tested are quite rare
      in early-onset AD. Amyloid beta protein (A beta) deposition was investigated in
      the temporal cortex of the R269H mutation case using end-specific monoclonal
      antibodies to detect the presence of A beta x-40 and A beta x-42 subspecies.
      Stereologically unbiased tangle and neuropil thread counts were obtained from the
      same region. R269H PS1 mutation was associated with early age of dementia onset,
      higher amounts of total A beta and A beta x-42, and increased neuronal
      cytoskeletal changes. Thus, if the changes observed on this case prove to be
      typical of PS1 mutations, PS1 mutations may impact both amyloid deposition and
      neurofibrillary pathology.

PMID- 9189044
TI  - Is there a genetic susceptibility locus for Parkinson's disease on chromosome
      22q13?
AB  - The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13),
      has been inconsistently associated with Parkinson's disease. Associations with
      CYP2D6 have either been absent altogether or have involved more than one
      polymorphism, many of which have the same metabolic effect on gene expression. We
      examined the association between CYP2D6 polymorphisms and Parkinson's disease in
      a case-control study and included 10 polymorphic dinucleotide repeat markers
      linked to CYP2D6 to determine whether the association was present or due to
      linkage disequilibrium. There was no association between any polymorphism of
      CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked
      to CYP2D6 were associated with the disease. These results provide evidence to
      suggest that there may be an unidentified locus for susceptibility to Parkinson's
      disease that is in linkage disequilibrium with dinucleotide repeat markers
      mapping near CYP2D6 on ch22q13.

PMID- 9189045
TI  - A double-blind controlled study of gabapentin and baclofen as treatment for
      acquired nystagmus.
AB  - We conducted a double-blind crossover trial comparing gabapentin (up to 900
      mg/day) to baclofen (up to 30 mg/day) as therapy for acquired nystagmus in 21
      patients. We measured visual acuity and the nystagmus before, and at the end of,
      2 weeks on each medication. For a group of 15 patients with acquired pendular
      nystagmus (APN), visual acuity improved significantly with gabapentin, but not
      with baclofen. Gabapentin significantly reduced APN median eye speed in all three
      planes, but baclofen did so only in the vertical plane. In 10 patients with APN,
      the reduction of nystagmus with gabapentin was substantial and 8 of these elected
      to continue taking the drug. In 6 patients with downbeat or torsional downbeat
      nystagmus, changes in median slow-phase eye speed were less consistent with both
      drugs, either increasing or decreasing, and being dependent on viewing
      conditions. Only 1 patient showed consistent reduction of median eye speed, and
      this was achieved by either drug. Our findings suggest that gabapentin may be an
      effective treatment for many patients with APN and that occasional patients with
      downbeat nystagmus will respond to gabapentin or baclofen.

PMID- 9189046
TI  - Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation
      of the alpha-tocopherol transfer protein gene.
AB  - The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein
      that is presumed to function in the intracellular transport of alpha-tocopherol,
      the most biologically active form of vitamin E. We studied 4 unrelated patients
      with autosomal recessive Friedreich-like ataxia who had isolated vitamin E
      deficiency. A point mutation was identified in all of them at position 101 of the
      gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG).
      Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of
      ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and
      decreased proprioceptive and vibratory sensations. Electrophysiological and
      pathological examinations showed that the cardinal sites affected were the
      central axons of dorsal root ganglion cells and the retina, with minor
      involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract.
      The vitamin E tolerance test performed showed that the absorption of vitamin E
      was normal but that its decrease from the serum was accelerated. Oral
      administration of vitamin E appeared to halt the progression of visual and
      neurological symptoms. We propose a new treatable syndrome of Friedreich-like
      ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.

PMID- 9189047
TI  - Treatment of Parkinson's disease: disagreements.

PMID- 9189048
TI  - Neuropsychological and behavioral changes and weight gain after medial
      pallidotomy.

PMID- 9189049
TI  - Rheumatoid arthritis and the balance of dietary N-6 and N-3 essential fatty
      acids.

PMID- 9189050
TI  - Should patients on hydroxychloroquine have their eyes examined regularly?

PMID- 9189051
TI  - Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis:
      association with susceptibility to, or severity of, disease?
AB  - Genetic factors associated with rheumatoid arthritis (RA) might involve variant
      tumour necrosis factor (TNF)-alpha genes. Therefore, polymorphisms at positions 
      308, -238, -376, -163 and +70 relative to the transcription initiation site were
      studied with respect to the susceptibility to, or severity of, RA. TNF-alpha
      genotypes of 283 RA patients and 116 healthy individuals were determined.
      Clinical data were obtained from patient files and questionnaires. The
      distribution of TNF-alpha alleles was similar in RA patients and healthy
      controls. With respect to disease severity, the TNF-alpha -238GA genotype was
      found to be associated with the absence of erosions [odds ratio (OR) 4.1,
      confidence interval 1.0-17]. In addition, this genotype was associated with a
      lower number of hand joints affected by erosions within the first 3 yr of disease
      onset compared to -238GG. The association between the -238 polymorphism and
      radiographic progression was independent of the presence of HLA-DR4. In line with
      this observation, the OR for the presence of erosions in patients with both risk
      factors (DR4 and -238GG) compared to patients who lack these factors was 11.1
      (1.8-6.8). No associations between the TNF-alpha -308, +70 and -376 alleles and
      susceptibility to, or severity of, RA could be demonstrated. Our data indicate
      that the TNF-alpha -238GA genotype is associated with decreased radiologically
      detectable progression of RA.

PMID- 9189052
TI  - Detection of protein and mRNA of various components of the NADPH oxidase complex
      in an immortalized human chondrocyte line.
AB  - The immortalized human chondrocyte cell line C-20/A4 has the ability to produce
      superoxide constitutively at low levels of 5.4 x 10(-2) nmol/min/10(6) cells
      (S.E.M. = +/-0.5, n = 30) and at raised levels upon stimulation with ionomycin
      and phorbol 12-myristate 13-acetate. Priming and anti-priming effects of
      interleukin (IL)-1 beta and IL-4, respectively, are also demonstrated. Reverse
      transcriptase polymerase chain reaction (RT-PCR) amplification using
      oligonucleotide primers to components of the NADPH oxidase enzyme complex showed
      mRNA expression of p22-phox, p40-phox and p47-phox. Western blot analysis using
      polyclonal antisera indicated the presence of the p47-phox p67-phox polypeptide
      components. These results show that the C-20/A4 cells contain an NADPH oxidase
      like complex, similar to that found in other cell types, which produces
      superoxide anions.

PMID- 9189053
TI  - The effect of sulphasalazine on neutrophil superoxide generation in rheumatoid
      arthritis.
AB  - The production of superoxide by the peripheral blood neutrophils of 19 patients
      with active rheumatoid arthritis was measured during treatment with
      sulphasalazine (SASP). The response to drug treatment was determined by change in
      plasma viscosity, CRP, early morning stiffness and articular index over a 10
      point scale. Of the 19 patients studied, eight were considered to have responded
      well to SASP and seven to have responded poorly or not at all. Over the treatment
      period, plateau levels of superoxide production fell in seven of the eight
      responders (P = 0.028) compared with a non-significant fall in 3/7 of the non
      responder groups. The initial rate of superoxide production also fell in the
      responder group, but this was not statistically significant. Initial values in
      both the responder and non-responder groups were comparable with those seen for
      normal controls. Analysis of drug levels showed all patients to be compliant with
      drug treatment; however, drug levels and neutrophil activity were not correlated.
      Studies of the effect of SASP and sulphapyridine on superoxide production in
      vitro showed no difference between good and poor responders. These results
      suggest that there is no inherent difference between good and poor responders
      regarding the susceptibility of their neutrophils to SASP. SASP's action on
      neutrophils, therefore, appears not to be its main mechanism of disease-modifying
      activity in RA.

PMID- 9189054
TI  - Long-term follow-up of 453 rheumatoid arthritis patients treated with
      methotrexate: an open, retrospective, observational study.
AB  - A total of 453 rheumatoid arthritis (RA) patients were followed up for 35.2 +/-
      27.9 months (range 3-106). The clinical parameters decreased significantly after
      6 months. Twenty-eight patients were in remission (6.4%). Rheumatoid factor (RF)
      positivity was less common in the group of patients in remission, with a higher
      frequency of visits and methotrexate (MTX) onset after 65 yr. There was a
      significant degradation of radiographic lesions (n = 60). A total of 101 patients
      (23.1%) stopped MTX, for toxicity (n = 61) and failure (n = 20). The onset of MTX
      after 65 yr, a low number of visits and the occurrence of side-effects were
      predictive of MTX withdrawal. A total of 259 patients (59.3%) had side-effects. A
      Ritchie's index < or = 10, a lower polymorphonuclear cell count and the absence
      of RF were predictive of side-effects. The probability of being on MTX at 5 yr
      was 73%. This study confirms the high efficacy of MTX in RA.

PMID- 9189055
TI  - Experimental Yersinia-triggered reactive arthritis: effect of a 3-week course of
      ciprofloxacin.
AB  - Lewis rats were injected i.v. with live Yersinia enterocolitica, resulting in 1-2
      weeks in an arthritis greatly resembling human reactive arthritis. Starting on
      day 3, 5, 10 or 13 after the bacterial inoculation, the rats were treated for 3
      weeks with 20 mg/kg/day of ciprofloxacin. The development of arthritis was
      completely prevented if the antibiotic treatment was started on day 3. In a group
      of rats treated with ciprofloxacin from day 5 onwards, 2/14 rats already showed
      mild arthritis at the time when the treatment was started. Antibiotic treatment
      cured the arthritis of these rats as well as that of one additional individual in
      this group which developed arthritis. No later exacerbations occurred. If the
      antibiotic treatment was started on day 10 or 13, i.e. at the time of well
      developed arthritis, no effect on arthritis was observed; rather, increased
      faecal excretion of Yersinia occurred following the antibiotic treatment. We
      conclude that experimental Yersinia reactive arthritis can be cured by
      antibiotics introduced at an early phase of arthritic development. Regarding
      acute human enterogenic arthritis, the decision on antibiotic treatment is not a
      straightforward matter. Our experimental results indicate that the earlier the
      treatment is started, the better the result, whereas late treatments seem to
      favour bacterial persistence.

PMID- 9189056
TI  - Ultrasonographic assessment of local steroid injection in Tietze's syndrome.
AB  - The purpose of this study was to investigate the value of ultrasonographic
      examination in the diagnosis of Tietze's syndrome and assessment of the changes
      in costal cartilage following local steroid injection. Nine patients with
      Tietze's syndrome and 20 normal subjects were studied consecutively. Ultrasound
      examination was performed using a Sonoline SL Siemens Machine with a linear 5 MHz
      small parts transducer and ATL Apogee 800 with a 10 MHz linear array transducer.
      The affected costochondral joint was injected with a combination of 15 mg of
      triamcinolone hexacetonide and 1 ml of 2% lidocaine. Ultrasound examination was
      performed following the clinical evaluation and repeated immediately after the
      injection, then 1 and 4 weeks later. Abnormal echo appearance was detected as an
      inhomogeneous increase in the echogenicity with intense broad posterior acoustic
      shadow. Hypoechogenicity and a decrease in the size of costal cartilage were
      observed 1 week after local steroid injection with absence of the posterior
      acoustic shadowing. Ultrasonographic examination of costal cartilage is easy and
      quick to perform. We believe that ultrasound should be the screening procedure of
      choice for Tietze's syndrome. Local steroid injection proved to be clinically
      safe and effective in the treatment of patients with Tietze's syndrome.

PMID- 9189057
TI  - Measuring health-related quality of life in rheumatoid arthritis: validity,
      responsiveness and reliability of EuroQol (EQ-5D).
AB  - The EuroQol (EQ-5D) generic health index comprises a five-part questionnaire and
      a visual analogue self-rating scale. The questionnaire may be used as a health
      index to calculate a 'utility' value or as a health profile. The validity,
      reliability and responsiveness of EQ-5D were tested in 233 patients with
      rheumatoid arthritis stratified by functional class. EQ-5D demonstrated moderate
      to high correlations with measures of impairment and high correlations with
      disability measures. Stepwise regression models showed that EQ-5D utility values
      and visual analogue scores were explained best as a function of pain, disability,
      disease activity and mood (R2 approximately 70%), although other variables (side
      effects, years of education) were required to explain the visual analogue scores.
      The EQ-5D health index and visual analogue scale are more responsive than any of
      the other measures, except pain and doctor-assessed disease activity. The
      reliability of the EQ-5D index and EQ-5D visual analogue scale is as good or
      better than that of all other instruments except the Health Assessment
      Questionnaire. Some patients with severe long-standing disease had health states
      which attracted utility values below zero, i.e. from a societal perspective they
      were regarded as being in states 'worse than death'. The practical and ethical
      implications of these utility valuations are discussed, and at present the
      utility values should be used and interpreted with caution. With this caveat, EQ
      5D is simple to use, valid, responsive to change and sufficiently reliable for
      group comparisons. It is of potential use as an outcome measure in clinical
      trials, audit and health economic studies, but further work is required on its
      performance in other clinical contexts and on the interpretation of the utility
      values.

PMID- 9189058
TI  - Auranofin.

PMID- 9189059
TI  - Guidance on ill health retirement.
AB  - Doctors are increasingly being asked by their patients to provide a report in
      support of an application for them to retire from work on the grounds of ill
      health. There is evidence that some applications may be motivated more by
      financial incentives than by ill health. Doctors should be wary of a conflict of
      interest, know the pension company's criteria for ill health retirement and
      provide objective medical evidence. The decision as to whether the patient
      fulfils the criteria is best left to another doctor who is acting as an advisor
      to the pension company.

PMID- 9189060
TI  - Rheumatology in Iceland.

PMID- 9189061
TI  - Soluble tumour necrosis factor receptor levels reflect coagulation abnormalities
      in systemic juvenile chronic arthritis.
AB  - The objective was to evaluate tumour necrosis factor (TNF) status in patients
      with systemic juvenile chronic arthritis (s-JCA). Plasma levels of TNF-alpha, and
      serum levels of soluble TNF receptor 1 and 2 (sTNFR1 and sTNFR2) were measured
      using specific immunoassays in 20 patients with s-JCA, 10 with polyarticular JCA
      and 15 with pauciarticular JCA, and in 20 controls comparable for age. In
      patients with active s-JCA, circulating levels of TNF-alpha, sTNFR1 and sTNFR2
      were significantly (P < 0.001) higher than those of controls. The levels of
      sTNFR1 and sTNFR2, but not those of TNF-alpha, were associated with the
      persistence and severity of systemic symptoms and were significantly correlated
      with prolongation of partial thromboplastin time and decrease in prothrombin
      activity. In two patients evaluated during a s-JCA-associated macrophage
      activation syndrome, a marked increase in sTNFR1 and sTNFR2 was found. Our
      results suggest that in s-JCA, TNF is involved in systemic manifestations, in the
      subclinical coagulation abnormalities, and in the development of the macrophage
      activation syndrome.

PMID- 9189063
TI  - Conversion disorders in adolescents: a practical approach to rehabilitation.
AB  - Young people with conversion disorders require a different treatment approach
      compared with those who have organic illness. This paper describes a team
      approach which is based on detailed assessment, explanation of the vicious cycle,
      accepting the patient's symptoms, working towards achievable goals, encouraging
      bravery, rewarding 'wellness' behaviour, ignoring abnormal behaviour and
      supervising re-integration into school.

PMID- 9189062
TI  - Suppression of fever and the acute-phase response in a patient with juvenile
      chronic arthritis treated with monoclonal antibody to tumour necrosis factor
      alpha (cA2).
AB  - Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of
      childhood. Although conventional therapy of JCA continues to improve, many
      patients experience long-term ill health as a result of their disease or
      treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the
      development of therapies designed to interfere in key disease processes. One such
      therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory
      cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in
      adult RA has led to impressive short-term suppression of disease, with a good
      safety profile. Here, we report the first use of cA2 in childhood arthritis,
      choosing a patient with severe systemic-onset JCA, resistant to conventional
      therapies. The patient received two i.v. infusions of cA2, each at a dose of 10
      mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid
      control of fever, anorexia and serositis, together with downregulation of
      interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase
      proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw
      no significant improvement in joint pain or tenderness. Our findings suggest that
      TNF-alpha is a mediator of fever and other systemic aspects of disease in
      systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further
      study.

PMID- 9189064
TI  - Ophthalmological monitoring for hydroxychloroquine toxicity: a scientific review
      of available data.

PMID- 9189065
TI  - Subcorneal pustular dermatosis (Sneddon-Wilkinson syndrome): another cutaneous
      manifestation of SAPHO syndrome?

PMID- 9189066
TI  - Supra-acetabular insufficiency fractures: role of fluoride treatment and vitamin
      D deficiency?

PMID- 9189067
TI  - Infertility may sometimes be associated with non-steroidal anti-inflammatory drug
      consumption.

PMID- 9189068
TI  - Cauda equina tumour presenting as atypical sciatica.

PMID- 9189069
TI  - Comment on the article 'Reactive arthritis, beta-haemolytic Streptococcus and
      Staphylococcus aureus' by D. N. Leitch and C. D. Holland.

PMID- 9189070
TI  - Very high serum ferritin levels in adult-onset Still's disease.

PMID- 9189071
TI  - Left ventricular diastolic function in scleroderma.

PMID- 9189072
TI  - Septic arthritis by Aspergillus fumigatus: a complication of corticosteroid
      infiltration.

PMID- 9189073
TI  - The importance of high-resolution computed tomography in the diagnosis of
      interstitial lung disease.

PMID- 9189074
TI  - Cyclical etidronate prevents spinal bone loss in early post-menopausal women.

PMID- 9189075
TI  - Rheumatoid arthritis: a possible sex bias in commencing second-line treatment.

PMID- 9189076
TI  - Surgical research and randomized trials.

PMID- 9189077
TI  - Laryngeal transplantation.

PMID- 9189078
TI  - Aggressive multimodality treatment for locally advanced irresectable rectal
      cancer.
AB  - BACKGROUND: Local failure rates are high for locally irresectable primary or
      recurrent colorectal cancer, even when chemoradiation therapy is employed. AIM:
      This review evaluates evidence supporting aggressive preoperative chemoradiation
      followed by maximal surgical resection and intraoperative radiation therapy to
      achieve disease control and cure for patients with locally advanced irresectable
      primary or recurrent rectal cancer. RESULTS: A 5-year survival rate of 42 per
      cent with a central failure rate of 2 per cent may be achieved in patients with
      locally irresectable primary rectal cancer. In patients with locally recurrent
      disease, these values at 5 years are 18 and 28 per cent respectively. The 5-year
      incidence of distant metastasis remains high, affecting 64 per cent of patients
      with primary cancer and 75 per cent of those with recurrent cancer. CONCLUSION: A
      disease-free surgical resection margin remains paramount to achieve cure.
      Encouraging trends exist, however, for further evaluation of multimodality
      therapy as a means of reducing local recurrence of disease.

PMID- 9189079
TI  - Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis
      after major surgical intervention: update of previous meta-analyses.
AB  - BACKGROUND: Previous meta-analyses comparing low molecular weight heparin (LMWH)
      and unfractionated heparin for thrombosis prophylaxis after surgical
      interventions need updating. METHODS: This is a publication-based meta-analysis
      of 36 double-blind studies including 16583 patients. Main outcome measures are
      incidence of deep vein thrombosis (efficacy) and wound haematoma (safety).
      RESULTS: In general surgery there is no increased efficacy in favour of LMWH
      (odds ratio (OR) 0.88, 95 per cent confidence interval (c.i.) 0.60-1.30) but
      there exists a higher incidence of bleeding complications (OR 1.47, 95 per cent
      c.i. 1.07-2.01). Low-dose LMWH is equally efficacious (OR 1.03, 95 per cent c.i.
      0.85-1.26) but safer than unfractionated heparin (OR 0.68, 95 per cent c.i. 0.56
      0.82). In orthopaedic surgery there is a trend towards an increased efficacy for
      LMWH (OR 0.83, 95 per cent c.i. 0.68-1.02) with equivalent safety (OR 0.96, 95
      per cent c.i. 0.68-1.36). CONCLUSION: A superiority of LMWH is suggested but
      heterogeneity might make generalizability to future patients questionable. A meta
      analysis on individual patient data should be the next step before randomizing
      additional patients in future trials.

PMID- 9189080
TI  - High-grade dysplasia in Barrett's oesophagus.
AB  - BACKGROUND: The management of high-grade dysplasia (HGD) in Barrett's oesophagus
      is a controversial and challenging problem. METHODS: An up-to-date review of the
      literature has been made using Index Medicus, the Medline database, and cross
      referencing of major articles on this subject. RESULTS: Diagnosis should be
      confirmed by a second expert pathologist. Repeat multiple jumbo biopsies and
      brushings need to be taken to reduce sample error and exclude associated invasive
      cancer. In young fit patients the advantages of surgery outweight the
      disadvantage of missing an early adenocarcinoma. Continued endoscopic
      surveillance may be more appropriate in elderly patients. New technology has
      increased the number of options. Early results of laser and multipolar
      electrocoagulation ablation of Barrett's epithelium are encouraging. Photodynamic
      therapy appears to be ideally suited to HGD and early cancers. CONCLUSION: A
      selective approach to the management of HGD on an individual patient basis should
      be adopted.

PMID- 9189081
TI  - CONSORT, randomized trials and the surgical scientific community.

PMID- 9189082
TI  - Candida antigen titre dilution and death after injury.
AB  - BACKGROUND: Candida infections affect outcome after injury. Candida antigen
      titres were used to detect these infections early. This study was undertaken to
      correlate Candida antigen titre dilution with conventional injury scoring and
      outcome after severe injury. METHODS: Candida antigen titres were determined by
      agglutination when clinically apparent source(s) of Candida were noted, when
      Candida was grown in culture of body fluids, or when unexplained clinical
      deterioration occurred. The findings were compared with the Injury Severity Score
      (ISS). RESULTS: Seventy-five seriously injured adults (median ISS 25 (range 18
      50)) developed raised Candida antigen titres. Multivariate analysis showed that
      age and Candida antigen titre correlated significantly with mortality, but not
      with each other. Culture evidence of Candida, or lack thereof, did not correlate
      with Candida antigen titre or mortality. Sixteen of 75 patients died, 14 from
      bacterial sepsis and none from Candida infection. CONCLUSION: In seriously
      injured adults, the mortality rate is related to raised Candida antigen titres.
      The association between Candida antigen titre and mortality, although real,
      remains unexplained.

PMID- 9189083
TI  - Role of macrophage overactivation in the development of acute pancreatic injury
      in rats.
AB  - BACKGROUND: An increase in systemic inflammatory mediators from stimulated
      leucocytes and macrophages has been noted during acute pancreatitis. The role of
      cytolytic inflammatory macrophages and potential mechanisms in the development of
      acute pancreatic injury and endothelial barrier dysfunction are less well
      defined. METHODS: Rats were challenged by an intraperitoneal injection of
      cytolytic or non-cytolytic inflammatory macrophage stimulators at various
      concentrations. The effects of oxygen free radicals, prostaglandin and
      extracellular calcium influx on macrophage-associated pancreatic endothelial
      compromise, measured by pancreatic intravascular plasma volume, pancreatic
      interstitial fluid volume, and the pancreatic extravascular human serum albumin
      distribution volume, were explored. RESULTS: Zymosan-induced overactivation of
      cytolytic inflammatory macrophages resulted in the development of acute
      pancreatic endothelial dysfunction in a dose- and time-dependent pattern. An
      increase in pancreatic water content and interstitial fluid volume was observed
      following a higher dose (0.5 mg/g) of concanavalin A without alteration in plasma
      lipase level, while thioglycollate medium did not compromise pancreatic
      endothelial barrier function. Oxygen free radicals, but also prostaglandins and
      extracellular calcium influx, seemed to be involved in macrophage overactivation
      induced pancreatic injury. CONCLUSION: Overactivation of cytolytic macrophages
      plays a role in the pathogenesis of pancreatic injury by initiating the
      development of endothelial barrier dysfunction. Multiple inflammatory mediators
      from overactivated macrophages act as intercellular signals between macrophages
      and the endothelium during acute pancreatic injury.

PMID- 9189084
TI  - Reoperative surgery for choledochal cysts.
AB  - BACKGROUND: Complications often follow if a choledochal cyst is treated simply by
      drainage, either internal or external. This study reviews 17 patients who had had
      previous cystoenterostomy (n = 9) or external drainage (n = 8) and who required
      reoperation and cyst excision. METHODS: The study was a retrospective review
      including ten women and seven men managed over 9 years. The indications for
      reoperation were stone formation (10 patients), pancreatitis (three), portal
      hypertension (two) and hepatic abscess (one); two patients were asymptomatic.
      RESULTS: Definitive surgery with cyst excision was possible in all patients who
      had previously had external cyst drainage and in seven of nine who had had
      previous cystoenterostomy. There were no deaths. Two postoperative biliary leaks
      and two duodenal fistulas resolved spontaneously. CONCLUSION: Excision of a
      choledochal cyst is possible and desirable even after a previous drainage
      operation. In severely ill patients with a complication of choledochal cyst,
      external drainage may be a preferable initial manoeuvre.

PMID- 9189085
TI  - Pilonidal cyst of the breast.

PMID- 9189086
TI  - Complete pancreatic encasement of the proximal hepatic portal vein: a previously
      undescribed congenital anomaly.

PMID- 9189087
TI  - Bile duct injury following laparoscopic cholecystectomy: referral pattern and
      management.
AB  - BACKGROUND: Laparoscopic cholecystectomy is associated with a higher incidence of
      bile duct injury than open cholecystectomy. This study reviews the management of
      bile duct injury in a tertiary hepatobiliary unit. METHODS: From 1991 to 1995, 27
      patients (18 women) of median age 49 (range 25-67) years were referred to this
      unit with bile duct injury following elective laparoscopic cholecystectomy.
      Laparoscopic cholecystectomy was described as 'uneventful' in 14 and 'difficult'
      in 13 patients; six injuries were recognized at operation. RESULTS: Patients were
      transferred a median of 26 (range 0-990) days after laparoscopic cholecystectomy,
      although initial symptoms were recorded a median of 3 (range 0-700) days after
      cholecystectomy. Fifteen patients underwent additional surgery before referral.
      Management before referral included surgical exploration (15 patients),
      endoscopic cholangiography (ERC) and stent insertion (three), external drainage
      of bile collections (five), and conservative management (five). Management after
      referral included surgical reconstruction (19 patients), laparotomy with drainage
      (one), percutaneous drainage (two), ERC and stent insertion (two), percutaneous
      cholangiography with dilatation and stent placement (three), and conservative
      management (two). One patient died and the median inpatient stay following
      referral was 14 (range 7-78) days. Ten of 15 patients who had surgery before
      referral required a further biliary reconstruction. After median follow-up of 30
      (range 3-60) months, four of nine patients with complex high injuries continue to
      have episodes of cholangitis and one patient has developed secondary biliary
      cirrhosis. CONCLUSION: Bile duct injury following laparoscopic cholecystectomy is
      a complex management problem and results in significant postoperative morbidity.
      Most patients referred after attempted repair require further reconstructive
      surgery, and patients with complex high injuries have a risk of long-term
      morbidity.

PMID- 9189088
TI  - Reinsertion of the distal common bile duct into the resection cavity during
      duodenum-preserving resection of the head of the pancreas for chronic
      pancreatitis.

PMID- 9189089
TI  - Prediction of postoperative decompensated liver function by technetium-99m
      galactosyl-human serum albumin liver scintigraphy in patients with hepatocellular
      carcinoma complicating chronic liver disease.
AB  - BACKGROUND: Preoperative technetium-99m galactosyl-human serum albumin (Tc-GSA)
      liver scintigraphy may predict postoperative decompensated liver function and its
      value has been investigated in patients having resection of hepatocellular
      carcinoma (HCC). METHODS: Hepatic uptake ratio of Tc-GSA (LHL15) was measured
      before operation in 30 patients. Postoperative complications were analysed
      retrospectively and compared with LHL15 values and other indicators evaluating
      hepatic function. RESULTS: The LHL15 of 22 patients without complications was
      0.91 or more, compared with 0.90 or less in the eight patients who had
      complications. Multifactorial analyses showed that LHL15 and Child-Pugh grade
      significantly predicted postoperative complications (P < 0.0001 and P = 0.0111
      respectively). LHL15 was a significant predictor of complications in patients
      with Child-Pugh grade B disease (n = 15, P = 0.0011). CONCLUSION: LHL15 was a
      reliable preoperative indicator of the risk of major postoperative complications
      in patients who had resection for HCC.

PMID- 9189090
TI  - Analysis of renal artery geometry may assist in the design of new stents for
      endovascular aortic aneurysm repair.
AB  - BACKGROUND: Endovascular repair of infrarenal aortic aneurysms is a feasible
      technique, but up to 30 per cent of patients may be excluded on the basis of a
      short proximal aortic neck. METHODS: A dissection study was performed on 65
      cadavers to measure the distance between the superior mesenteric and renal artery
      ostia, and to document the points of origin of the renal arteries. RESULTS: The
      interostial distance did not differ significantly between aneurysmal and non
      aneurysmal aortas (P = 0.90 for the left renal artery; P = 0.72 for the right).
      The median distance was 0.7 cm. The renal arteries originated between 2 and 4
      o'clock on the left and between 9 and 10 o'clock on the right. CONCLUSION: The
      relative consistency of the anatomy in this region may allow the development of a
      new stent which would increase the number of patients suitable for endovascular
      repair.

PMID- 9189091
TI  - Major vascular injury during laparoscopy.

PMID- 9189092
TI  - Improving the preoperative assessment of varicose veins.

PMID- 9189093
TI  - Flow cytometric analysis of p53 oncoprotein expression in cutaneous melanoma.
AB  - BACKGROUND: Mutation of the p53 tumour suppressor gene is thought to represent a
      significant step in the development of over half of all human cancers.
      Qualitative investigations of p53 protein in cutaneous melanoma suggest that
      overexpression is more common than in other tumours. This study analysed p53
      protein expression using flow cytometry as a quantitative assay. METHODS:
      Expression of p53 protein was assayed in ten benign melanocytic naevi (BMN) and
      50 surgically excised ethanol-fixed melanomas. Nuclei were stained for the p53
      protein with Pab1801 and analysed using flow cytometry. Protein expression was
      further correlated with clinicopathological parameters. RESULTS: None of the BMN
      was immunopositive for p53. Forty-one of the 50 melanomas stained positively. The
      overall median positivity for p53 in primary melanoma was 12.8 per cent compared
      with 22.5 per cent in metastatic disease. No association was found between p53
      expression and Breslow thickness or presence of nodal and skin metastases.
      Overexpression of p53 was associated with ulceration, mitotic figures and
      lymphocytic infiltration, and there was a striking increase of p53 expression
      with age. Expression of p53 was inversely correlated with disease-free interval.
      CONCLUSION: Although overexpression of p53 is common in melanoma, there was no
      association with major clinical parameters such as Breslow thickness and overall
      survival. The association found between p53 and other clinicopathological
      features suggests that the tumour suppressor gene does play a role in the
      evolution of melanoma.

PMID- 9189094
TI  - Totally stapled restorative proctocolectomy.
AB  - BACKGROUND: Totally stapled restorative proctocolectomy (TSRP) has simplified
      ileoanal pouch surgery but few reports exist concerning experience with the
      technique. A retrospective study of operative and functional data in a
      consecutive series of patients undergoing TSRP was undertaken. METHODS: TSRP with
      J pouch formation was attempted in 103 patients between 1988 and 1995 (for
      ulcerative colitis (87 patients), familial adenomatous polyposis coli (nine),
      slow transit constipation (six) and hereditary non-polyposis colorectal cancer
      (one). Three technical failures resulted in 100 patients available for
      assessment. Case notes were reviewed together with functional assessment by
      clinical interview and/or postal questionnaire. RESULTS: Median operating time
      was 200 min, intraoperative blood loss 360 ml and hospital stay 12 days. There
      were no operative deaths. All but five patients (95 per cent) had loop ileostomy
      formation with subsequent reversal. There were 29 complications, six of which
      required further surgical intervention. Six pouches were excised and two patients
      had a temporary defunctioning ileostomy. Five patients were rediagnosed as having
      Crohn's disease, of whom four underwent subsequent pouch excision. Pouchitis (in
      the absence of Crohn's disease) occurred in eight patients (8 per cent). In 60
      patients with at least 12 months of established function, median day and night
      stool frequencies were 5 and 1 respectively. Functional evaluation in 49 patients
      (82 per cent) revealed regular use of antidiarrhoeal medication in 21, urgency in
      17, and total continence by day and night in 37 and 35 respectively. Fifty-three
      patients (88 per cent) were satisfied with the overall long-term outcome.
      CONCLUSION: TSRP is safe, has simplified a technically difficult operation and
      gives good long-term functional results.

PMID- 9189095
TI  - Acute abdomen due to anthrax.

PMID- 9189096
TI  - Outcome of 200 restorative proctocolectomy operations: the John Radcliffe
      Hospital experience.
AB  - BACKGROUND: Restorative proctocolectomy is now the operation of choice for the
      definitive management of ulcerative colitis and familial adenomatous polyposis
      (FAP). METHODS: A total of 200 patients (117 male, 83 female) underwent
      restorative proctocolectomy over a 12-year period. Information in a dedicated
      prospective database was supplemented by chart review. Some 177 had ulcerative
      colitis, 13 had indeterminate colitis and seven had FAP. Pouch designs were two
      loop J (n = 142), four-loop W (n = 45) and three-loop S (n = 13). The majority
      (73.5 per cent) had a stapled ileoanal anastomosis and 139 patients had a
      defunctioning ileostomy. RESULTS: There were no deaths. Early morbidity (less
      than 30 days after operation) included 76 complications in 71 patients (35.5 per
      cent), of which 35 were related to the pouch itself. Long-term follow-up data
      were available for 196 patients at a median of 27 months. Sixteen pouches (8.0
      per cent) have been excised. Mean daytime frequency was 4.5 (range 1-15). Of 175
      patients with colitis, 42 (24.0 per cent) had one or more episodes of pouchitis.
      CONCLUSION: Continuous improvements in operative technique have simplified the
      procedure, and functional results, although variable, have generally been
      acceptable.

PMID- 9189097
TI  - Spontaneous resolution of histologically proven liver metastases from colorectal
      cancer.

PMID- 9189098
TI  - Perianal sepsis in children.
AB  - BACKGROUND: Perianal sepsis is a relatively common surgical problem in children
      and yet the contribution of rare aetiological factors, the frequency of fistula
      formation complicating perianal abscess, the significance of bacteriological
      findings and the optimum treatment of fistula in ano are poorly understood.
      METHODS: A consecutive series of 58 children (51 boys, seven girls) with a
      perianal abscess or fistula attending a tertiary referral centre over a 4-year
      period was reviewed. RESULTS: Thirty-eight children (34 boys, four girls),
      ranging in age from 1 month to 12 years, presented with an abscess. After
      treatment, three developed a further abscess but only four developed a fistula.
      Fistula formation only occurred in those with enteric bacterial infection. Of 24
      children with a perianal fistula five required further surgery for recurrence,
      four of whom were initially treated by fistulotomy. In most patients, the fistula
      was simple, low and direct, and treatment by fistulectomy resulted in
      significantly fewer recurrences. Apart from Crohn's disease, identifiable
      aetiological factors were rare. CONCLUSION: Perianal sepsis is most common in
      otherwise healthy boys under 2 years of age. Abscess is best treated by incision
      and drainage, and fistulectomy is successful for the small proportion who develop
      a fistula.

PMID- 9189099
TI  - Laparoscopic resection of the colon and rectum for cancer.
AB  - BACKGROUND: Laparoscopically-assisted resection for large bowel cancer is
      technically feasible. Sixty-six patients who had resection of the colon or rectum
      for cancer have been audited prospectively. METHODS: Clinical and pathological
      data were collected prospectively as part of the ongoing Concord Hospital
      colorectal cancer project. Patients were followed up for a median of 29 months.
      RESULTS: In 57 of 66 patients in whom laparoscopic resection was attempted the
      operation was completed laparoscopically. Three patients died from perioperative
      myocardial infarction. The median postoperative stay was 14 days. There was a
      high incidence of postoperative respiratory and cardiac complications. One
      patient developed a port-site metastasis. CONCLUSION: There was no obvious
      benefit from laparoscopically-assisted resection of large bowel cancer in these
      patients.

PMID- 9189100
TI  - p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis.
AB  - BACKGROUND: The genetic alterations in patients with familial adenomatous
      polyposis (FAP) and duodenal adenomas are poorly characterized when compared with
      data relating to colorectal tumorigenesis in the same patients. METHODS: Point
      mutation of the K-ras oncogene and point mutation and overexpression of the TP53
      tumour suppressor gene were investigated in 32 duodenal polyps (seven without
      mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately
      dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53
      mutation or positive p53 staining were not found in duodenal polyps without
      histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in
      three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53
      immunostaining, and mutation of the TP53 gene was found in one moderately
      dysplastic adenoma. p53 protein overexpression in duodenal adenomas was
      significantly more frequent than mutation of either K-ras or TP53 (P < 0.01).
      CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with
      FAP. Overexpression may indicate DNA damage and thus an early step in
      tumorigenesis.

PMID- 9189101
TI  - Intragastric endoscopic surgery using the transanal endoscopic microsurgery
      technique.

PMID- 9189102
TI  - TUR syndrome and endoscopic transanal resection: no evidence for a clinically
      important association in 38 procedures.
AB  - BACKGROUND: The TUR syndrome is well described after transurethral resection of
      the prostate. Endoscopic transanal resection (ETAR) is increasingly used to
      remove rectal lesions. METHODS: A prospective study of 38 ETARs in 21 patients
      was carried out over 2 years. Each patient was observed for symptoms and signs of
      TUR syndrome, and each had serial venous blood sampling and subsequent
      biochemical and haematological analysis during the perioperative period. RESULTS:
      No symptoms or signs typical of TUR syndrome were recorded. However, analysis of
      the biochemical variables using the Kruskal-Wallis one-way analysis of variance
      showed that there were statistically significant (P < 0.05) subclinical changes
      during the 24 h following the procedure affecting levels of serum sodium,
      potassium, total protein, albumin, lactate dehydrogenase, glycine, ammonia and
      serum osmolality. CONCLUSION: The changes in the electrolyte concentrations,
      although statistically significant, were not of the same magnitude as described
      previously in the TUR syndrome. The risk of a TUR-type syndrome in ETAR is small
      and serial blood tests, as detailed above, may safely be omitted.

PMID- 9189104
TI  - Long-term expandable stent as a definitive treatment for benign rectal stenosis.

PMID- 9189103
TI  - Detection of circulating tumour cells and nodal metastasis by reverse
      transcriptase-polymerase chain reaction technique.
AB  - BACKGROUND: In the search for occult metastases in lymph nodes or circulating
      tumour cells, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay
      was developed to detect tumour-specific splice variants of the transcript of the
      CD44 gene. The assay was highly sensitive and could detect ten tumour cell per
      10(5) leucocytes. METHODS: RNA was purified from peripheral blood (n = 24) and
      regional lymph nodes (n = 14) from patients with colorectal cancer. Complementary
      DNA was made and amplified using primers specific for the CD44 gene. Southern
      blotting with exon-specific probes was used to enhance the sensitivity. RESULTS:
      Tumour cells were detected in peripheral blood samples in four patients and lymph
      nodes in nine, in one of whom conventional histology had not detected tumour
      cells. CONCLUSION: This technique may be useful in the early diagnosis of primary
      or metastatic tumours, in assessing prognosis and in detecting residual disease
      after treatment.

PMID- 9189105
TI  - Randomized controlled trial with sequential design of laparoscopic versus
      conventional appendicectomy.
AB  - BACKGROUND: A prospective study including 272 patients with suspected
      appendicitis was performed. The aims were to evaluate the representativity of the
      study group and to compare diagnostic and therapeutic laparoscopy with
      conventional appendicectomy. METHODS: The study was an open, randomized, single
      centre trial with sequential design. One hundred and eight patients were
      randomized between laparoscopy or conventional appendicectomy, of whom 84 had
      acute appendicitis. Duration of postoperative convalescence was the major
      endpoint. RESULTS: The study patients were representative of the eligible
      population regarding age and stage of appendicitis. The risk of unnecessary
      appendicectomy was significantly (P = 0.03) lower after laparoscopy. The mean
      difference in duration of postoperative convalescence was 4.7 days in favour of
      of laparoscopic appendicectomy (P = 0.07), and 26 min in duration of operation in
      favour of conventional appendicectomy (P < 0.01). No differences were detected in
      postoperative hospital stay, pain assessment or complications. CONCLUSION: The
      laparoscopic procedure is at least as good as conventional appendicectomy.
      Initial laparoscopy reduces the rate of misdiagnosis.

PMID- 9189106
TI  - Randomized placebo-controlled trial of teicoplanin in the antibiotic prophylaxis
      of infection following manipulation of burn wounds.
AB  - BACKGROUND: Burn wound surgery or change of dressings commonly causes
      bacteraemia. The use of antibiotic prophylaxis has not been tested adequately in
      a controlled trial. METHODS: A randomized double-blind placebo-controlled study
      was performed to determine the effect on Gram-positive bacteraemia and clinical
      outcome of a single dose of teicoplanin (12 mg/kg intravenously) given at burns
      surgery or change of dressings. RESULTS: A total of 134 patients were entered
      into the study, representing 220 episodes of dressing or debridement (110
      episodes in each group). There was a significant difference between the groups
      with respect to perioperative Gram-positive bacteraemia: eight episodes (7 per
      cent) in the teicoplanin group versus 51 (46 per cent) in the placebo group (P <
      0.001). However, good clinical outcome was similar in both groups (80 of 110
      versus 77 of 110 respectively, P = 0.7). Only eleven patients had bacteraemia
      caused by Gram-negative species alone. Bacteriological response in terms of wound
      culture showed no significant difference between the groups: 63 (57 per cent) of
      110 episodes versus 58 (53 per cent) of 110 respectively respectively.
      CONCLUSION: Prevention of Gram-positive bacteraemia did not affect postoperative
      recovery.

PMID- 9189107
TI  - The NIM-2 nerve integrity monitor in thyroid and parathyroid surgery.

PMID- 9189108
TI  - Surgical treatment for carcinoma of the oesophagus in Chinese language
      publications.
AB  - INTRODUCTION: This review is a meta-analysis of Chinese language publications on
      surgical treatment for oesophageal cancer. METHODS: Between 1980 and 1994, 17,815
      patients had surgery for carcinoma of the oesophagus. The male:female ratio was
      3.9:1 and mean age was 51.9 (range 16-80) years. RESULTS: Mean resectability rate
      was 86.7 per cent and hospital mortality rate was 3.8 per cent. The crude 5-year
      and 10-year survival rates for all patients were 29.6 and 16.4 per cent
      respectively. For patients with stage 0 and stage I tumours, the 5-year survival
      rate was 95 and 89 per cent respectively, significantly greater than that for
      those with stage II, III and IV tumours (19.4 per cent, P < 0.01). The 5-year
      survival rate of all 2226 patients with tumour resection after radiotherapy was
      38.0 per cent. There was no significant difference in survival following
      combination therapy compared with surgery alone. When compared with a report for
      the interval 1940-1979, there was no significant difference in the resectability,
      hospital mortality or 5-year survival rates. CONCLUSION: Oesophageal carcinoma
      remains a disease with dismal prognosis but surgery still offers the best chance
      of long-term survival. Adjuvant therapy has not yet proved an advantage in terms
      of survival but can be useful for palliation. Mass screening might improve
      survival but only in a population with a high incidence of oesophageal carcinoma.

PMID- 9189109
TI  - Surgery as a 'last resort' option for active variceal bleeding further
      complicated by iatrogenic oesophageal perforation.

PMID- 9189110
TI  - Splenic irradiation for the treatment of hypersplenism from congestive
      splenomegaly.

PMID- 9189111
TI  - Long-term results of the Angelchik prosthesis for gastro-oesophageal reflux.
AB  - INTRODUCTION: Between 1982 and 1989, 46 patients had insertion of an Angelchik
      prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent)
      subsequently had the prosthesis removed, all but one for intractable dysphagia.
      METHODS: Thirty-six of the original patients were followed by questionnaire, and
      32 of these had a barium marshmallow swallow investigation. RESULTS: A high
      proportion of patients (20 of 26) with a prosthesis in situ had symptoms of
      dysphagia. On objective evaluation by marshmallow swallow, the transit time was
      significantly slower than that of an age-matched control group (P < 0.01), but
      showed no significant deterioration with time compared with previous
      postinsertion studies. CONCLUSION: The Angelchik prosthesis causes long-term
      dysphagia in a high proportion of patients, severe enough in one-quarter to
      necessitate its removal. Its continued use cannot, therefore, be recommended.

PMID- 9189112
TI  - Endoscopic stenting for recurrent malignant gastric outlet obstruction.

PMID- 9189113
TI  - Influence of tumour penetration on period of death after gastric cancer surgery.

PMID- 9189114
TI  - Disappointing long-term results of laparoscopic adjustable silicone gastric
      banding.

PMID- 9189115
TI  - Laparoscopically-assisted total pharyngolaryngo-oesophagectomy.

PMID- 9189116
TI  - Knot-free subcuticular suture.

PMID- 9189117
TI  - Reduced long-term survival following major peptic ulcer haemorrhage.

PMID- 9189118
TI  - Double stapled transabdominal anastomosis for one-stage resection of acute
      sigmoid volvulus.

PMID- 9189119
TI  - A better bridge for loop stomas.

PMID- 9189120
TI  - Surgery for biliary obstruction by tumour thrombus in primary liver cancer.

PMID- 9189121
TI  - Pilonidal sinus: experience with the Karydakis flap.

PMID- 9189122
TI  - Cancer staging technique holds promise.

PMID- 9189123
TI  - It's time to stop crying and do something.

PMID- 9189124
TI  - Technetium-99m-tetrofosmin for parathyroid scintigraphy: a comparison with
      sestamibi.
AB  - Parathyroid scintigraphy with the new myocardial perfusion radiopharmaceutical
      99mTc-tetrofosmin was compared with 99mTc-sestamibi scintigraphy using early and
      delayed imaging. METHODS: The two preparations were administered on different
      days to the same 16 patients suffering from primary hyperparathyroidism. Anterior
      view gamma camera planar imaging (10-min acquisition) was performed in the period
      between 5 min and 3 hr after administration of the radiopharmaceutical. For most
      of the patients, a pertechnetate image of the thyroid was available for eyeball
      comparison when reading the tetrofosmin and sestamibi images. Imaging results
      were compared with those from histopathological examination after surgery.
      RESULTS: On early images, all the adenomas visualized with sestamibi were equally
      well seen with tetrofosmin and vice versa. In 6 of 11 scintigraphically detected
      neck adenomas, delayed imaging improved the adenoma visualization with sestamibi.
      In contrast, this differential washout was never seen with tetrofosmin.
      Histopathological examination of excised tissue specimens after neck exploration
      (15 patients) or thoracotomy (one patient) revealed a parathyroid adenoma in all
      16 patients. Our 12 scintigraphic findings were true-positives, while the
      remaining four scintigraphies were false-negatives, giving a diagnostic
      sensitivity of 75% with both preparations. The mediastinal adenoma was detected
      in a patient with a history of two unsuccessful neck explorations and one
      unsuccessful thoracotomy. CONCLUSION: Tetrofosmin has the same success rate as
      sestamibi for detection of parathyroid adenomas on scintigrams acquired
      immediately after injection. In contrast to sestamibi, delayed imaging has no
      diagnostic impact. Moreover, the thyroid/ parathyroid differential washout of
      sestamibi failed in 5 of 11 neck adenomas here detected, indicating that delayed
      sestamibi washout is an unreliable diagnostic criterion. Therefore, whether
      sestamibi or tetrofosmin is preferred for parathyroid scintigraphy, thyroid
      scintigraphy seems mandatory.

PMID- 9189125
TI  - Comparison of parathyroid imaging with technetium-99m-pertechnetate/sestamibi
      subtraction, double-phase technetium-99m-sestamibi and technetium-99m-sestamibi
      SPECT.
AB  - The ability of 99mTc-pertechnetate/sestamibi subtraction, double-phase 99mTc
      sestamibi and 99mTc-sestamibi SPECT imaging to localize abnormal parathyroid
      tissue was compared. METHODS: Fifty-five consecutive patients had parathyroid
      imaging before surgery for hyperparathyroidism. Imaging consisted of 99mTc
      pertechnetate pinhole images of the neck followed by 99mTc-sestamibi pinhole
      images of the neck and parallel-hole images of the neck and chest (early images).
      Within 2.5-4.0 hr later pinhole images of the neck, parallel-hole and SPECT
      images of the neck and chest were obtained (late images). Nodular foci of
      increased sestamibi activity were considered abnormal. RESULTS: The sensitivity
      for abnormal parathyroid glands by visual comparison of early images and
      pertechnetate images was 72%-75%, late images and pertechnetate images was 73%
      78% and double-phase (early and late) sestamibi images was 62%-65%; computer
      subtraction of pertechnetate from early images was 71%-74%; and SPECT imaging was
      79%. The sensitivity for parathyroid adenomas was 89%-98%, while the sensitivity
      for hyperplastic parathyroid glands was only 47%-58%. CONCLUSION: Late imaging,
      computer subtraction and SPECT may not be necessary since they provided only
      marginal improvements on visual comparison of early sestamibi with pertechnetate
      images. Double-phase sestamibi imaging was less sensitive, so baseline thyroid
      imaging with pertechnetate is recommended.

PMID- 9189126
TI  - Radionuclide parathyroid imaging.

PMID- 9189127
TI  - PET imaging of brain tumor with [methyl-11C]choline.
AB  - This article describes a new method of [11C]choline synthesis for intravenous
      injection. We aimed at the utilization of this compound for brain tumor imaging
      with PET. METHODS: After [11C]carbon dioxide production in a cyclotron and the
      subsequent [11C]methyl iodide synthesis, [methyl-11C]choline was synthesized by
      the reaction of [11C]methyl iodide with "neat" dimethylaminoethanol at 120
      degrees C for 5 min. Purification was achieved by evaporation of the reactants
      followed by passage of the aqueous solution of the product through a cation
      exchange resin cartridge. The time required for overall chemical processing,
      excluding the cyclotron operation, was 15 min. Radiochemical yield was > 98%.
      Radiochemical purity was > 98%. Chemical purity was > 90% (dimethylaminoethanol
      was the only possible impurity). Specific radioactivity of the product was > 133
      GBq/mumol. The whole body distribution was examined in rabbits with PET. Clinical
      studies were performed in patients with brain tumor using PET after intravenous
      injection of 370 MBq of [11C]choline. RESULTS: In rabbits,[11C]choline was taken
      up from blood by various tissues very rapidly, and the radioactivity remaining in
      blood became almost negligible 5 min after intravenous injection. Taking
      advantage of this characteristic, we obtained stable tissue distribution images
      of human brain using PET. In patients with brain tumor, PET produced clearly
      delineated positive images of the tumors. CONCLUSION: Carbon-11-choline can be
      used for obtaining clear images of brain tumor in PET.

PMID- 9189128
TI  - Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody
      biodistribution in patients with colorectal tumors.
AB  - Copper-67 has comparable beta-particle emissions to that of 131I, but it displays
      more favorable gamma emission characteristics for application in
      radioimmunotherapy (RIT). This study investigates the potential of 67Cu-labeled
      monoclonal antibody (MAb) 35 for RIT of colorectal carcinoma. METHODS:
      Biokinetics of simultaneously injected 67Cu- and 125I-labeled MAb35 were studied
      in six patients scheduled for surgery of primary colorectal cancer. RESULTS:
      Whole-body clearance (T 1/2) of 67Cu, estimated from sequential anterior and
      posterior whole-body scans and corrected for decay of 67Cu, was 41 hr. Serum
      clearance of 67Cu was faster (27.41 hr) than that of 125I (38.33 hr). Mean tumor
      uptake of the 67Cu-labeled compound (0.0133% ID/g) exceeded that of 125I (0.0095%
      ID/g), and tumor-to-blood ratios were higher for 67Cu than for 125I, with
      averages of 6.07 and 2.41, respectively. The average 67Cu/125I ratio was 1.9 for
      tumor uptake, 0.7 for blood and 2.6 for tumor-to-blood ratios. Nonspecific liver
      uptake of 67Cu as calculated from whole-body scans was high in four patients, up
      to 25% of residual whole-body activity at 48 hr, but did not increase with time.
      We also observed some nonspecific bowel activity, as well as moderate to high
      uptake in benign polyps. CONCLUSION: Copper-67-labeled MAb35 is more favorable
      than its radioiodine-labeled counterpart for RIT of colorectal carcinoma due to
      higher tumor-to-blood ratios, but the problem of nonspecific liver and bowel
      uptake must first be overcome. The absolute accumulation of activity in tumor
      remains low, however, so the probability of cure with this compound alone is
      questionable. The use of 67Cu as one component of a multimodality adjuvant
      treatment seems to remain the most appropriate application for RIT.

PMID- 9189129
TI  - Clinical impact of somatostatin receptor scintigraphy in the management of
      patients with neuroendocrine gastroenteropancreatic tumors.
AB  - Somatostatin receptor scintigraphy (SRS) has been used for the detection of
      gastroenteropancreatic (GEP) tumors. This study evaluates the clinical impact of
      SRS in GEP tumor detection and its therapeutic implications on patient
      management. METHODS: We prospectively studied 160 patients with biologically
      and/or histologically proven GEP tumors. Before SRS, patients were classified
      into three groups: gastrointestinal (Group 1; n = 90) patients without known
      metastases; (Group 2; n = 59) patients with metastases limited to the liver;
      (Group 3; n = 11) patients with known extrahepatic metastases. The scintigraphic
      data were compared to the radiological findings. RESULTS: In Group 1, without
      known metastases, conventional imaging detected 53 primary sites in 44 patients:
      SRS was positive in 68% of these sites and discovered 4 additional primary tumors
      in 3 patients and 16 metastases in 14 patients. Conventional imaging was negative
      in 46 patients: SRS discovered 47 new sites in 36 patients. In Group 2, SRS
      confirmed liver metastases in 95% of patients and discovered 45 new sites in 36
      of these patients. In Group 3, SRS disclosed 11 new sites in 7 patients. These
      results modified patient classification in 38 cases (24%). Surgical therapeutic
      strategy was changed in 40 patients (25%). CONCLUSION: Somatostatin receptor
      scintigraphy improves tumor detection, has major clinical significance and should
      be performed systematically for staging and therapeutic decision making in
      patients with GEP tumors.

PMID- 9189130
TI  - Phase I/II clinical radioimmunotherapy with an iodine-131-labeled anti
      carcinoembryonic antigen murine monoclonal antibody IgG.
AB  - The aim of this study was to determine, in a Phase I/II clinical trial, the
      pharmacokinetics, dosimetry and toxicity, as well as antitumor activity, of the
      131I-labeled murine anti-carcinoembryonic antigen (CEA) monoclonal antibody, NP-4
      (IgG1 subtype). METHODS: A total of 57 patients with CEA-expressing tumors (29
      colorectal, 9 lung, 7 pancreas, 6 breast and 4 medullary thyroid cancer
      patients), mostly in very advanced stages, were treated. The patients underwent a
      diagnostic study (1-3 mg of IgG and 8-30 mCi of 131I) to assess tumor targeting
      and to estimate dosimetry, followed by the therapeutic dose (4-23 mg and 44-268
      mCi), based on the radiation dose to the red marrow. Imaging was performed from 4
      240 hr postinjection (planar and SPECT). Blood and whole-body clearance were
      determined; radiation doses were calculated by the Medical Internal Radiation
      Dose scheme. RESULTS: Red marrow doses ranged from 45 to 706 cGy, and whole-body
      doses ranged from 31 to 344 cGy. Differences in pharmacokinetics were found
      between different types of CEA-producing tumors: blood T 1/2 was significantly
      lower in colorectal cancer when compared to all other tumor types (21.4 +/- 11.1
      hr versus 35.8 +/- 13.2 hr, p < 0.01), as was also whole-body t 1/2.
      Myelotoxicity was dose-limiting, and its severity was related to the types of
      prior therapy and extent of bone marrow involvement. In patients without prior
      radiation or chemotherapy, marrow doses as high as 600 cGy were tolerated without
      evidence of dose-limiting toxicity. No major toxicity to other organs was
      observed. Tumor doses were inversely related to the tumor mass and ranged between
      2 and 218 cGy/mCi. Modest antitumor effects were seen in 12 of 35 assessable
      patients (1 partial remission, 4 minor/mixed responses and 7 with stabilization
      of previously rapidly progressing disease). CONCLUSION: These results suggest
      that prior chemotherapy or external beam radiation is an important risk factor
      for the development of hematological toxicity in radioimmunotherapy and that
      higher radiation doses may be delivered to tumors of patients without prior
      therapy compromising the bone marrow reserve. The different and, in the
      individual cases, unpredictable clearance rates suggest the necessity of
      dosimetry-based treatment planning rather than mCi/m2 dosing. Small tumors seem
      to be more suitable for radioimmunotherapy because of their favorable dosimetry,
      but to achieve better therapeutic results in patients with bulky disease, the
      application of higher, potentially myeloablative doses is indicated.

PMID- 9189131
TI  - Visualizing ocular melanoma using iodine-123-N-(2-diethylaminoethyl)4
      iodobenzamide SPECT.
AB  - Radiolabeled benzamides have recently been introduced for the detection of
      melanoma. We evaluated the potential clinical applicability of 123I-N-(2
      diethylaminoethyl) 4-iodobenzamide ([123I]IDAB) for SPECT imaging of ocular
      melanoma. METHODS: Fourteen patients were studied, 10 with or suspected of
      malignant ocular melanoma and four with ocular naevi. All patients underwent
      SPECT imaging of the head and whole-body scintigraphy 4-5 hr after injection of
      170 MBq [123I]IDAB. RESULTS: A definite tracer hyperfixation was observed in the
      pathological eye in 9 of 10 (90%) patients with ocular melanoma. The pathological
      to-normal eye ratio averaged 1.46 (range 1.07-2.86). The melanoma nature of the
      scintigraphic lesions was confirmed after enucleation in eight cases and by
      clinical evolution in two. A false-negative scan was reported in a patient with a
      small and hypochromic lesion. In patients with ocular naevi, no false-positive
      scintigrams were documented. CONCLUSION: Iodine-123-IDAB scintigraphy may
      contribute significantly to decide about enucleation in cases where some doubt
      persists with conventional techniques.

PMID- 9189132
TI  - Thallium-201 SPECT in the diagnosis of head and neck cancer.
AB  - The accuracy of SPECT with 201Tl-chloride for the diagnosis of primary tumors,
      lymph node metastases and recurrences in head and neck cancer was evaluated for
      clinical applicability. METHODS: SPECT images, obtained 60 min after
      administration of 150 MBq 201Tl-chloride, were compared with clinical, CT and/or
      MRI and histology results. In addition, whole-body images were obtained to detect
      distant metastases. RESULTS: In 79 patients studied for primary tumors
      (principally larynix, hypopharynx, oropharynx, nasopharynx and oral cavity),
      201Tl SPECT correctly identified 69 of 73 (95% versus 88% for CT/MRI)
      histologically confirmed malignancies including 63 squamous-cell carcinomas. The
      method localized four occult naso- and oropharynx carcinomas not seen on CT/MRI
      and was correctly negative in two patients without tumor and in three of four
      patients with no confirmed primary tumor in the head and neck. With respect to
      regional spread, only patients who had cervical lymph node dissection were
      evaluated, and the findings were recorded per side of the neck. Thallium-201
      SPECT correctly identified metastases in 31 of 36 neck dissections with proven
      lymph node involvement (86%), was correctly negative in nine and false-positive
      in one. Although the sensitivity of CT/MRI was clearly higher (97%), considerably
      more false-positive cases affected its accuracy (81% versus 87% for SPECT). In 30
      patients investigated for recurrences, 201Tl SPECT correctly identified 27 of 29
      microscopically confirmed tumor sites (93%) and was correctly negative in seven.
      Sensitivity of CT/MRI was lower (76%), and a greater number of false-positives
      (seven versus three for SPECT) further decreased its accuracy (64% versus 87% for
      SPECT). Distant metastases were detected in five patients. CONCLUSION: Thallium
      201 SPECT appears to be an accurate method for the diagnosis of head and neck
      cancer. The method is particularly useful for detection of occult head and neck
      tumors and for assessing recurrences. It also may be of complementary value in
      the staging of primary tumors, in the differentiation of metastatic from reactive
      lymph nodes in the neck and, on the basis of whole-body scanning, for screening
      of distant metastases.

PMID- 9189133
TI  - Vasoactive intestinal peptide and somatostatin receptor scintigraphy for
      differential diagnosis of hepatic carcinoid metastasis.
AB  - We report a case of a hepatic carcinoid metastasis mimicking a hemangioma on
      ultrasound and on CT. Indium-111-DTPA-D-Phe-1-octreotide (111In-OCT) and 123I
      vasoactive intestinal peptide (123I-VIP) receptor images suggested a carcinoid
      metastasis of the liver. The final diagnosis was established histopathologically.
      The differential diagnosis of liver lesions is discussed.

PMID- 9189134
TI  - Perfusion and blood-pool scintigraphy in the evaluation of head and neck
      hemangiomas.
AB  - We investigated the sensitivity and specificity of perfusion and blood-pool
      scintigraphy in the detection of head and neck hemangiomas and evaluated their
      histopathologic types. METHODS: Perfusion and blood-pool scintigraphy with 99mTc
      red blood cells (RBCs) or 99mTc-human serum albumin combined with DTPA (HSA-D)
      were used to evaluate 51 head and neck lesions clinically suspected of being
      hemangiomas in 48 patients. Thirty-three of the 51 lesions were subsequently
      histologically confirmed to be hemangiomas, whereas the remaining 18 were
      histologically diagnosed as other lesions. RESULTS: Perfusion and blood-pool
      scintigraphy correctly diagnosed 30 of 33 hemangiomas as being hemangiomas but
      could not detect the remaining 3 hemangiomas. Perfusion and blood-pool
      scintigraphy correctly diagnosed 12 of 18 lesions as nonhemangiomas, but the
      remaining 6 lesions were misdiagnosed as hemangiomas. Thus, the sensitivity for
      detecting hemangiomas was 91%, with a specificity and accuracy of 67% and 82%,
      respectively. Twenty-five (89%) of 28 cavernous or venous hemangiomas
      demonstrated normal activity on the perfusion images and increased activity on
      the delayed blood-pool images, whereas the remaining 3 (11%) showed normal
      activity on both perfusion and blood-pool images. Finally, 5 of 5 (100%)
      capillary or recemose hemangiomas showed increased activity on the perfusion and
      blood-pool images. CONCLUSION: Perfusion and blood-pool scintigraphy demonstrated
      sufficiently high sensitivity but relatively low specificity for detecting head
      and neck hemangiomas. Additionally, perfusion and blood-pool scintigraphy can
      clearly differentiate between cavernous and venous hemangiomas and capillary and
      recemose hemangiomas and are extremely useful for the detection and evaluation of
      head and neck hemangiomas.

PMID- 9189135
TI  - Somatostatin receptor scintigraphy of malignant somatostatinoma with indium-111
      pentetreotide.
AB  - This article describes the visualization of a pancreatic somatostatinoma and
      liver metastases using 111In-pentetreotide imaging in a patient with
      somatostatinoma syndrome. A 61-yr-old woman with gallbladder stones, diabetes,
      weight loss, diarrhea and steatorrhea, immunohistochemical diagnosis of
      somatostatinoma (liver biopsy) and high plasma values of somatostatin was studied
      by somatostatin receptor scintigraphy. Six sites of focal abnormal 111In
      pentetreotide hyperfixation were found: three in the liver and three in the
      pancreatic area. This case report demonstrates that in vivo detection of
      somatostatinoma with somatostatin receptor imaging is possible in the presence of
      high levels of circulating somatostatin, suggesting that receptor downregulation
      has not occurred.

PMID- 9189136
TI  - False-positive FDG-PET imaging of the thymus of a child with Hodgkin's disease.
AB  - During the evaluation of a child who had completed treatment for Hodgkin's
      disease, a PET study strongly suggested recurrent disease in the mediastinum.
      Biopsies were obtained and revealed normal thymic tissue only, with no evidence
      of recurrent disease. The ongoing difficulty in establishing accurate disease
      status in patients treated for Hodgkin's disease is discussed, along with
      recommendations for treating pediatric patient populations.

PMID- 9189137
TI  - Scintigraphic monitoring of reticuloendothelial system in patients with type 1
      Gaucher disease on enzyme replacement therapy.
AB  - The purpose of this study was to define the scintigraphic pattern of marrow
      replacement and changes in reticuloendothelial activity after enzyme replacement
      therapy in patients with Gaucher disease. METHODS: Forty patients underwent
      baseline whole-body imaging with 99mTc-sulfur colloid and evaluation of liver and
      spleen volume with CT or magnetic resonance imaging. Thirty-seven of the 40
      patients were treated with enzyme replacement. Therapeutic responses of central
      and peripheral bone marrow and the changes in pulmonary uptake of 99mTc-sulfur
      colloid were assessed visually at 1-4 yr after the start of therapy. Changes in
      liver and spleen volumes were analyzed quantitatively. The initial pattern of
      marrow involvement was correlated with disease severity (based on baseline blood
      counts and liver and spleen volumes). RESULTS: Baseline studies revealed that 38
      of 40 (95%) and 28 of 40 (70%) of the patients in this study had abnormal
      peripheral and central marrow activity, respectively. Twenty of 24 evaluable
      patients (83.3%) on therapy showed regression of peripheral bone marrow activity
      to a more proximal location in the lower extremities, increased ratio of
      pelvic/proximal femoral activity to distal activity or both. Fourteen of 19
      treated patients (73.7%) with abnormal initial central marrow activity showed
      detectable improvement in central bone marrow activity as a result of therapy. In
      patients with initial lung uptake of 99mTc-sulfur colloid, 91% showed complete
      resolution of the uptake after therapy. These changes in colloid uptake and
      distribution were associated with significant reductions in liver and spleen
      volumes and improvements in blood counts. CONCLUSION: Most patients with Gaucher
      disease demonstrate increased central bone marrow activity and regression of
      activity in peripheral bone marrow with enzyme replacement therapy. Additionally,
      the abnormal phagocytic pulmonary activity observed before therapy in many of the
      patients resolves.

PMID- 9189139
TI  - Rapid imaging of experimental infection with technetium-99m-DTPA after anti-DTPA
      monoclonal antibody priming.
AB  - Antibodies accumulate nonspecifically in infectious foci due to the locally
      increased vascular permeability. This study describes a method of infection
      imaging in which 99mTc-DTPA (diethylenetriaminepentaacetic acid) is trapped at
      the target by a previously administered anti-DTPA monoclonal antibody. DTIn1.
      METHODS: Rats with Staphylococcus aureus-infected calf muscle were injected
      intravenously with DTIn1. Two to 24 hr after the DTIn1 injection, 99mTc-DTPA was
      injected intravenously. In separate experiments, excess DTIn1 was cleared from
      the circulation 2 hr after injection with bovine serum albumin (BSA)-DTPA-In,
      galactosylated BSA-DTPA-In, goat antimouse IgG or avidin. Additionally, the
      effect of DTIn1 dose on 99mTc-DTPA abscess uptake was determined in a three-step
      protocol. The distribution of the radiolabels was studied by gamma counting of
      dissected tissue and gamma camera imaging. RESULTS: Priming with DTIn1 resulted
      in specific retention of 99mTc-DTPA in the abscess. Such 99mTc-DTPA abscess
      uptake was not dependent on the interval between the DTIn1 and the 99mTc-DTPA
      injection: Optimal 99mTc-DTPA abscess uptake was already achieved within a 2-hr
      time span between the DTIn1 and DTPA injections. However, relatively high 99mTc
      DTPA background was observed due to slowly clearing DTIn1-99mTc-DTPA complexes.
      Background reduction with various agents had a prominent effect on DTIn1 as well
      as 99mTc-DTPA biodistribution. The best reduction was obtained using BSA-DTPA-In.
      Optimal 99mTc-DTPA abscess uptake in the three-step protocol was obtained at
      higher DTIn1 doses (> 100 micrograms). CONCLUSION: Infectious foci in a rat model
      can be imaged earlier with extremely low background levels after priming with
      DTIn1, followed by BSA-DTPA-In and imaging with 99mTc-DTPA, as compared with
      directly labeled IgG.

PMID- 9189138
TI  - Extracorporeal whole-blood immunoadsorption enhances radioimmunotargeting of
      iodine-125-labeled BR96-biotin monoclonal antibody.
AB  - This study investigates the efficacy of tumor radioimmunotargeting with 125I
      labeled BR96-biotin monoclonal antibody using a new method, whole-blood
      immunoadsorption (WBIA), based on direct adsorption of unbound monoclonal
      antibody (MAb) from blood without preceding separation of plasma. METHODS: Highly
      tumor-reactive, internalizing, chimeric BR96 MAb of isotype IgG1 binds to a tumor
      associated Lewis-type (Le(Y)) cell surface antigen. Forty-six Brown Norwegian
      male rats were inoculated intramuscularly and beneath the liver or kidney capsule
      with syngeneic rat colon carcinoma BN7005, expressing Lewis-type antigen, and
      investigated. The rats were injected intravenously with 3.5-4.5 MBq 125I-labeled
      BR96-biotin. Twenty of the rats underwent WBIA starting 5 or 12 hr after
      injection. About six blood volumes were passed through an avidin-gel adsorption
      column during 2 hr. RESULTS: By using WBIA, whole-body radioactivity was reduced
      by 50%, and plasma activity by 85%. Both directly after completion of WBIA and 33
      hr later, the activity uptake in tumors manifested only a nonsignificant decrease
      as compared with corresponding controls (p > 0.05) and had approximately similar
      time-activity curves. Uptake ratios for tumor (T):bone marrow, T:liver, T:kidney
      and T:lung were enhanced 2.3- to 3.5-fold in all three tumor models, as compared
      with controls. The ratio of liver tumor to bone marrow was improved from 10:1 to
      30:1. CONCLUSION: This new method of WBIA yields significantly improved
      radioimmunotargeting of highly tumor-reactive, internalizing MAb BR96.

PMID- 9189140
TI  - In vivo hybridization of technetium-99m-labeled peptide nucleic acid (PNA).
AB  - Hybridization of a radiolabeled single-stranded DNA oligonucleotide with its
      single-stranded complement in vivo has not yet been convincingly demonstrated. A
      contributing factor may be unfavorable in vivo properties of the phosphodiester
      and phosphorothioate DNAs. Peptide nucleic acid (PNA) oligomers have been
      reported to possess in vivo properties more suitable for radiopharmaceutical
      applications. METHODS: We have radiolabeled an amine-derivatized 15-base PNA
      oligomer with 99mTc through a modified MAG3 chelator. RESULTS: The ability of the
      PNA to hybridize in vitro with its complement appeared to be unimpaired after
      conjugation and radiolabeling. Size-exclusion, high-performance liquid
      chromatography (HPLC) analysis of 37 degrees C serum after 24 hr of incubation
      showed the radiolabel to be present predominately as labeled PNA with indications
      of labeled serum proteins and a low molecular weight catabolite. Whole-body
      clearance in mice was rapid, with 50% of the label eliminated in about 2 hr.
      After 2.5 hr, the highest uptake (kidneys) was only 1.5% of the injected dose/g;
      less than 0.07%/g was present in all sampled tissues at 24 hr. To evaluate in
      vivo hybridization, beads were implanted subcutaneously in both thighs of normal
      mice. In the left thigh only, the beads were conjugated with complementary single
      stranded PNA. At 23 hr following intraperitoneal administration of the labeled
      PNA, the left/right thigh radioactivity ratio was 6:1. Whole-body images at this
      time showed only bladder, kidneys and the left thigh. CONCLUSION: Unlike the
      radiolabeled DNAs investigated in this laboratory, 99mTc-PNA displays stability
      and pharmacokinetic properties suitable for eventual use as radiopharmaceuticals.

PMID- 9189141
TI  - MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's
      disease.
AB  - In this study, we assessed the accuracy and reliability of MRI-guided SPECT
      measurements of medial temporal lobe blood flow in Alzheimer's disease (AD).
      METHODS: Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO
      SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in
      eight control subjects and eight patients with probable AD. Intraoperator
      reliability was assessed by repeated alignment and measurement by one experienced
      operator. Accuracy was assessed by examining two subjects with fiducial markers.
      RESULTS: The alignment error was less than 1 SPECT pixel size (3.5 mm) and the
      coefficient of variation in repeated measures of medial temporal-to-cerebellar
      CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF
      ratios between eight control subjects and eight AD patients was 12%. Also by
      using three-dimensional seed-grow defined healthy brain reference regions, there
      were significant differences between control subjects and AD patients in medial
      temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal
      ROIs were smaller in the AD patients. The best separation between AD patients and
      control subjects was achieved by combining MRI measurements of atrophy and SPECT
      measurements of CBF. CONCLUSION: These data show that the accuracy and
      reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow
      the detection of changes in AD. Also, a direct comparison of structural and
      functional changes is possible by this methodology, which might improve the early
      diagnosis of AD.

PMID- 9189142
TI  - Comparative quantitation of cerebral blood volume: SPECT versus PET.
AB  - Quantification of cerebral blood volume (CBV) measured by SPECT has been used for
      evaluation of cerebral hemodynamics in patients with cerebrovascular diseases.
      The accuracy of such quantification, however, has not been validated with PET.
      METHODS: CBV was assessed using SPECT and in vitro 99mTc-labeled red blood cells
      and PET with the 15O steady-state inhalation method and C15O. In 23 patients with
      carotid artery disease, we measured hemispheric (including cortical and
      subcortical areas) CBV, and in 11 patients, we measured regional CBV in small
      cortical regions. We further evaluated the interhemispheric and inter-regional
      asymmetry of CBV with both methods. RESULTS: Quantitative values of both
      hemispheric and regional CBV measured by SPECT were significantly correlated with
      those measured by PET in the same patients. There was a significant correlation
      between the side-to-side asymmetry of CBV for both methods. CONCLUSION: This
      study demonstrates usefulness and the accuracy of SPECT for quantitative CBV
      assessment in comparison with the less widely available PET procedures.

PMID- 9189143
TI  - Reduction of cerebellar glucose metabolism in advanced Alzheimer's disease.
AB  - Although regional cerebral metabolism and blood flow in Alzheimer's disease (AD)
      have been studied extensively with PET and SPECT, few reports have been concerned
      with cerebellar metabolism or perfusion in Alzheimer's disease. To evaluate
      cerebellar glucose metabolism in Alzheimer's disease patients, we studied the
      cerebellar and cerebral metabolic rate for glucose (CMRglc) using 2[18F]fluoro-2
      deoxy-D-glucose (18F-FDG) and PET. METHODS: Sixty-eight patients with Alzheimer's
      disease and 13 age-matched normal control subjects were examined. According to
      scores obtained on the Mini-Mental State Examination (MMSE), Alzheimer's disease
      patients were classified into three groups: severe (n = 9), moderate (n = 33) and
      mild (n = 26). RESULTS: The cerebellar glucose metabolism in the severe
      Alzheimer's disease group was significantly lower (cerebellar glucose metabolism:
      5.71 +/- 0.62 mg/100 g/min) than that of the control group (6.85 +/- 0.66 mg/100
      g/min), while temporal and parietal CMRglc were much more decreased. The
      cerebellar glucose metabolism in the mild and moderate Alzheimer's disease groups
      also showed lower levels than that of the control group, but the differences did
      not reach significant levels. Like other cortical CMRglc, the cerebellar glucose
      metabolism correlated with cognitive impairments. CONCLUSION: In severe
      Alzheimer's disease, cerebellar glucose metabolism is significantly reduced. The
      method of analysis using normalization of regional metabolic data to cerebellar
      values may be liable to err in severe Alzheimer's disease patients.

PMID- 9189144
TI  - Discriminative use of SPECT in frontal lobe-type dementia versus (senile)
      dementia of the Alzheimer's type.
AB  - Dementia of the Alzheimer's type [(S)DAT] and dementia with frontal features
      (FLD) are nosological entities with different prognoses and presumed
      pathophysiology. There is a need for noninvasive differential diagnostic tools.
      To evaluate whether SPECT perfusion imaging could discriminate between these
      neurodegenerative disorders, we performed a comparative study. METHODS: SPECT
      scans using 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO) of 21 patients
      with FLD were compared with those obtained in a group of 19 age- and severity
      matched patients suffering from (S)DAT. Brain SPECT perfusion deficits were
      scored by visual qualitative analysis with respect to location, lateralization
      and severity. A total severity score of cerebral hypoperfusion (maximal value =
      18) was calculated by adding all severity scores (scored between 0 and 3; 0 = no
      perfusion deficit; 1 = 13%-30% hypoperfusion; 2 = 30%-50%, hypoperfusion and 3 =
      > 50% hypoperfusion including breaching of the cortex) for right and left
      frontal, parietal and temporal lobes. Moreover, bifrontal hypoperfusion (Fa) was
      scored, yielding a value between 0 and 6 by adding the two frontal severity
      scores. RESULTS: No significant correlation was found between MMSE scores and
      total severity scores on SPECT. A statistically significant correlation was found
      between the Middelheim frontality score and frontal severity score. Statistically
      more significant bilateral hypoperfusion of the parietal lobes was found in the
      (S)DAT group. Conversely, bifrontal hypoperfusion was found more in the FLD
      group. Stepwise logistic regression analysis identified the severity of bifrontal
      hypoperfusion as the most significant contributing parameter to correctly
      classifying (S)DAT versus FLD on SPECT. The probability of predicting (S)DAT
      based on the SPECT scan is calculated with the following formula: [equation: see
      text] Using this equation, a value above 0.5 was predictive for (S)DAT and a
      calculated value under 0.5 was predictive for FLD. Using this model, 81% of the
      FLD group and 74% of the (S)DAT were correctly classified. CONCLUSION: Technetium
      99m-HMPAO SPECT may help in discriminating FLD from (S)DAT. Bifrontal
      hypoperfusion was found to be the most powerful predictor of clinical
      classification. Further validation of the presented logistic regression model is
      warranted.

PMID- 9189145
TI  - Imaging beta-adrenoceptors in the human brain with (S)-1'-[18F]fluorocarazolol.
AB  - We evaluated the suitability of fluorocarazolol for in vivo studies of cerebral
      beta-adrenoceptors because (S)-1'-[18F]fluorocarazolol has a higher affinity to
      beta-adrenoceptors than to serotonergic receptors (pKi beta 1 9.4, beta 2 10.0,
      5HT1A 7.4, 5HT1B 8.1) and rapidly crosses the blood-brain barrier. METHODS: The
      (S)-[18F]fluorocarazolol (74 MBq, > 37 TBq/mmol) was intravenously administered
      to healthy volunteers on two separate occasions with an interval of at least 1
      wk. The initial injection was without pretreatment, but before the second
      injection, the volunteers received the beta blocker (+/-)-pindolol (3 x 5 mg
      orally, during 18 hr). The brain was studied with a PET camera in dynamic mode.
      RESULTS: Uptake of radioactivity delineated gray matter and was particularly high
      in the posterior cingulate, precuneus and striatum. Low uptake occurred in the
      thalamus, whereas the lowest uptake was observed in the white matter of the
      corpus callosum. After pindolol pretreatment, uptake was reduced and its
      distribution became homogeneous throughout the brain. The ratio of total-to
      nonspecific binding was about 2 at 60 min, increasing to 2.5-2.75 at longer
      intervals. CONCLUSION: Fluorocarazolol is the first radioligand that can
      visualize cerebral beta-adrenoceptors and may enable monitoring of these binding
      sites during disease.

PMID- 9189146
TI  - Cerebral sparganosis: increased uptake of technetium-99m-HMPAO.
AB  - Cerebral sparganosis is an extremely rare intracranial parasitic infectious
      disease. We report findings of 99mTc-HMPAO cerebral perfusion SPECT in a case
      with cerebral sparganosis. SPECT revealed an irregularly shaped area with
      markedly increased 99mTc-HMPAO uptake in the parasitic infectious region of the
      cerebrum. Both white and gray matter was involved, the white matter involved
      predominantly. Decreased perfusion to the right cerebellum, suggesting cross
      cerebellar diaschisis, was also demonstrated. This article illustrates that
      cerebral sparganosis is one of the causes of increased 99mTc-HMPAO uptake in the
      cerebrum and should be considered clinically if present.

PMID- 9189147
TI  - Right and left ventricular volume and ejection fraction by tomographic gated
      blood-pool scintigraphy.
AB  - Tomographic techniques separate overlying structures, permitting measurements of
      absolute ventricular volumes. The purpose of this study was to determine absolute
      right and left ventricular volume and ejection fraction measurements with
      tomographic gated equilibrium blood-pool scintigraphy (TMUGA) compared to MRI and
      conventional planar scintigraphy. METHODS: Eighteen patients were studied.
      Ventricular volumes for TMUGA and MRI were calculated by modified Simpson's rule.
      TMUGA regions were defined by constraints including phase analysis, intensity
      threshold and visual inspection. MRI studies were acquired with a fast gradient
      echo, ECG-gated, breath-hold technique and boundaries were defined by a
      semiautomated contour method. Conventional gated first-pass radionuclide
      angiography (FP) and planar gated equilibrium blood-pool scintigraphy (PMUGA)
      were performed for RV EF and LV EF, respectively. RESULTS: TMUGA absolute right
      ventricular volumes showed excellent-correlation with MRI for both right
      ventricular volumes (r = 0.91, slope = 0.90, s.e.e. = 15.7) and left ventricular
      volumes (r = 0.96, slope = 0.88, s.e.e. = 18.2). For left ventricular ejection
      fraction, TMUGA also showed excellent correlation with MRI (r = 0.94, slope =
      1.10, s.e.e. = 9.0) and planar MUGA (r = 0.97, slope = 1.23, s.e.e. = 6.2). For
      right ventricular ejection fraction, TMUGA showed good correlation with both MRI
      (r = 0.88, slope = 0.79, s.e.e. = 6.0) and first-pass planar scintigraphy (r =
      0.86, slope = 1.2, s.e.e. = 7.9). CONCLUSION: Tomographic gated blood-pool
      scintigraphy absolute right and left ventricular volumes and ejection fractions
      show good correlation with accepted techniques. Further studies are necessary to
      define the reproducibility of this method.

PMID- 9189148
TI  - Ambulatory monitoring of left ventricular function: walk and bicycle exercise in
      congestive heart failure.
AB  - The aim of this study was to assess changes in left ventricular (LV) function
      during 6-min walk test and cardiopulmonary exercise by continuous radionuclide
      monitoring in patients with congestive heart failure (CHF). METHODS: Seventeen
      patients with CHF and 10 normal subjects underwent monitoring of LV function
      (Vest) during 6-min walk test and during bicycle exercise with combined analysis
      of pulmonary gas exchange. During cardiopulmonary exercise, all parameters of LV
      function were measured at rest, at the anaerobic threshold (AT) and at peak
      oxygen uptake (peak VO2). RESULTS: In the normal subjects, during the walk test,
      heart rate (HR), ejection fraction (EF), end-diastolic volume (EDV), cardiac
      output (CO) and stroke volume (SV) significantly increased from rest to peak (all
      p < 0.001), while end-systolic volume (ESV) significantly decreased from rest to
      peak (p < 0.001). In patients with CHF, during the walk test, HR, EDV, ESV and CO
      significantly increased from rest to peak (p < 0.001), EF significantly decreased
      from rest to peak (p < 0.001) and SV did not show significant change. During
      cardiopulmonary exercise, normal subjects showed a significant increase in HR and
      CO, from rest to AT and from AT to the peak VO2 (p < 0.001). EF, EDV and SV
      significantly increased from rest to AT (p < 0.001), with no significant change
      from AT to peak VO2. ESV decreased from rest to AT (p < 0.001), showing no
      significant change from AT to peak VO2. In patients with CHF, HR, CO, ESV and EDV
      increased significantly from rest to AT (p < 0.001) and from AT to peak VO2 (p <
      0.001). EF and SV did not show significant changes from rest to AT, showing a
      significant decrease from AT to peak VO2 (p < 0.001). CONCLUSION: Vest can be
      used to evaluate cardiac responses during 6-min walk test and cardiopulmonary
      exercise in patients with CHF. In such patients, significant impairment of LV
      function is already present during submaximal physical exercise becoming more
      evident during the anaerobic phases of bicycle exercise.

PMID- 9189149
TI  - Alterations of myocardial sympathetic innervation in response to hypoxia.
AB  - The effects of altitude hypoxia on myocardial sympathetic nerve function were
      assessed in rats using metaiodobenzylguanidine (MIBG). METHODS: To estimate the
      change in uptake-1 function induced by hypoxia, three sets of rats were submitted
      to 5-, 7- and 21-day hypoxia (hypobaric chamber at 410 Torr) and one set of
      control rats was injected with 25 muCi of 123I-MIBG. Four hours later, the rats
      were killed and 123I activity was counted in both ventricles. The proportion of
      MIBG fixed in the myocardium through the norepinephrine (NE) transporter (uptake
      1) was evaluated indirectly in 5-day hypoxic and controls rats by the injection
      of desipramine before 123I-MIBG administration. Myocardial perfusion was
      evaluated in 5-day hypoxic rats and controls by 201Tl injection. RESULTS:
      Myocardial 123I-MIBG activity was 0.253% +/- 0.036% kg dose/g-1 in controls and
      was decreased (0.188% +/- 0.029% kg dose/g-1, p = 0.001) in 5-day hypoxic rats.
      This decrease was not related to a change in cardiac perfusion. The decrease in
      MIBG uptake existed before the appearance of cardiac hypertrophy. Desipramine
      decreased MIBG uptake by 48% in controls and 17% in hypoxic rats, suggesting that
      the decrease predominantly affected MIBG uptake by the NE transporter.
      CONCLUSION: Chronic hypoxia leads to a decrease in myocardial NE-uptake-1
      function. This finding suggests that altered tissue oxygen supply could play a
      role in the decreased cardiac MIBG uptake reported in human cardiomyopathies.

PMID- 9189150
TI  - Quantification of left ventricular function with thallium-201 and technetium-99m
      sestamibi myocardial gated SPECT.
AB  - Myocardial gated SPECT with 99mTc-sestamibi has been used to quantify left
      ventricular function. The purpose of this study was to determine if myocardial
      gated SPECT with 201Tl was possible and reliable to quantify left ventricular
      function. METHODS: One hundred and four patients referred for a myocardial
      perfusion study were included. Myocardial gated SPECT acquisition was performed
      15 min after the intravenous injection of 111 MBq (3mCi) 201Tl and at 1 hr
      postinjection of 925 MBq (25 mCi) 99mTc-sestamibi. A commercially available
      automated myocardial gated SPECT processing software was used. Parameters
      evaluated were left ventricular ejection fractions (LVEF), end-diastolic volumes
      (EDV), end-systolic volumes (ESV) and stroke volumes (SV). RESULTS: The
      correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi
      was: r = 0.93 for LVEF, 0.92 for EDV, 0.96 for ESV and 0.68 for SV. CONCLUSION:
      Myocardial gated SPECT quantification of left ventricular function with 201Tl was
      possible and as reliable as gated SPECT with 99mTc-sestamibi. There was excellent
      correlation between gated SPECT with 201Tl and gated SPECT with 99mTc-sestamibi.
      In addition to assessment of myocardial perfusion, myocardial function and
      viability can be quantified in a single gated 201Tl study.

PMID- 9189151
TI  - Pulmonary perfusion and density gradients in healthy volunteers.
AB  - The goal of this study was to measure regional pulmonary perfusion using SPECT
      and transmission tomography for attenuation correction and density measurements.
      METHODS: Regional pulmonary perfusion was studied after intravenous injection of
      radiolabeled particles in 10 supine healthy volunteers using SPECT. Transmission
      tomography was used to correct for attenuation, measure lung density and
      delineate the lungs. The effects of attenuation correction on pulmonary perfusion
      gradients were investigated. RESULTS: In perfusion measurements not corrected for
      attenuation, we found significant perfusion gradients in the direction of gravity
      but also significant gradients at isogravitational level. After correction for
      attenuation, the gravitational gradient was significantly greater than before
      correction, and gradients at isogravitational level were no longer observed.
      Perfusion in the ventral lung zone was half of that in the dorsal lung zone. Mean
      lung density was 0.28 +/- 0.03 g/ml, and density showed a significant increase in
      the direction of gravity and at isogravitational level. CONCLUSION: We found that
      SPECT perfusion studies of the lung not corrected for attenuation gave a false
      impression of nongravitational gradients and underestimate the gradient that is
      gravity-dependent. Transmission tomography, used for attenuation correction, also
      quantifies lung density and shows gravity dependent and nondependent density
      gradients.

PMID- 9189152
TI  - Impaired permeability in radiation-induced lung injury detected by technetium-99m
      DTPA lung clearance.
AB  - This study evaluates the use of the 99mTc-DTPA aerosol lung clearance method to
      investigate radiation-induced lung changes in eight patients undergoing
      radiotherapy for lung or breast carcinoma. The sensitivity of the method was
      compared with chest radiography for detecting radiation-induced changes in the
      lung, regional alterations within (irradiated region) and outside (shielded
      region) the treatment ports, effect of irradiated lung volume, and dependence on
      time after radiotherapy. METHODS: Serial DTPA lung clearance studies were
      performed before the first radiation treatment (baseline), then weekly during a 5
      to 7-wk course, and up to 12 times post-therapy over periods of 56-574 days. The
      total activity deposited in the lungs for each study was approximately 150
      microCi (approximately 5.6 MBq). DTPA clearance, expressed in terms of the
      biological half-time, t 1/2, was computed from the slopes of the least-squares
      fit regression lines of the time-activity curves for the first 10 min for
      irradiated and shielded lung regions. RESULTS: Major findings include: (a)
      significant and early DTPA t 1/2 changes were observed in all patients during and
      after radiotherapy; (b) changes in DTPA t 1/2 values were observed in both
      irradiated and shielded lung regions in all patients suggesting a radiation
      induced systemic reaction; (c) changes in DTPA t 1/2 values were correlated (p <
      0.05) with the irradiated lung volumes; (d) significantly reduced DTPA t 1/2
      values were observed in three patients who subsequently presented with clinical
      symptoms and/or radiographic changes consistent with radiation pneumonitis (t1/2
      felt to 19% +/- 6% of baseline values, compared with 64% +/- 17% in the remaining
      patients [p < 0.01]); (e) the onset of decreased DTPA t 1/2 values in these three
      patients occurred 35-84 days before clinical symptoms and/or radiographic
      changes; and (f) DTPA t 1/2 tended to approach baseline values with time after
      radiotherapy, suggesting a long-term recovery in lung injury. CONCLUSION: These
      observations show significant and early alterations in DTPA lung clearance during
      and after radiotherapy that may provide a sensitive assay to monitor changes in
      radiation-induced lung injury and may facilitate early therapeutic intervention.

PMID- 9189153
TI  - Chronic exertional compartment syndrome in lower legs: localization and follow-up
      with thallium-201 SPECT imaging.
AB  - The purpose of this study was to ascertain whether 201Tl SPECT imaging of the leg
      is useful in precise localization of the ischemic compartment involved in chronic
      exertional compartment syndrome (CECS). METHODS: Imaging and quantitative
      analyses of postexercise 201Tl SPECT leg examinations were retrospectively
      performed in nine patients with clinically diagnosed CECS and eight control
      subjects. Imaging and quantitative criteria for the ischemic compartment were
      decreased 201Tl perfusion less than the lower limits of normal, which were
      defined as 2 s.d. below the mean percentage uptake of the control subjects. The
      SPECT imaging results were compared with those of quantitative analysis,
      postoperative SPECT images and clinical diagnoses. RESULTS: Postexercise normal
      legs had nonuniform 201Tl distribution in both legs and in the four compartments.
      Lower limits of normal mean percentage 201Tl uptake were about 60% for the
      anterior compartment and about 50% for the other three compartments.
      Redistribution was observed in 67% of normal compartments in the control
      subjects. The SPECT images demonstrated 16 ischemic compartments in eight of the
      nine patients. The SPECT results were consistent with those of quantitative
      analysis. There were discrepancies between the clinical and SPECT diagnoses in
      six legs (33% of the 18 legs) of five patients. Postoperative SPECT demonstrated
      201Tl perfusion was improved in all involved compartments for that fasciotomy was
      performed. CONCLUSION: Thallium-201 SPECT imaging of the legs can easily provide
      precise localization of the ischemic compartment, which is demonstrated as
      decreased 201Tl distribution on the stress image. This technique is promising for
      the screening and follow-up of CECS.

PMID- 9189154
TI  - Feasibility of a rapid method to evaluate platelet survival time.
AB  - The purpose of this study was to evaluate the feasibility of a shorter method of
      performing platelet kinetic studies with respect to the conventional 8-9-day
      approach. METHODS: We studied 41 patients (28 women, 13 men; mean age 52 yr) with
      primary idiopathic thombocytopenic purpura (ITP) (n = 20), secondary ITP (n = 9),
      HCV associated thrombocytopenia (n = 9), splenectomy (n = 1) and hairy-cell
      leukemia (n = 1). The patients were in a steady-state of platelet turnover.
      Initial platelet counts ranged from 19 to 302 x 10(9)/liter (mean value = 83).
      Platelet survival times (PST) were measured from the blood radioactivity
      disappearance curve of 111In-oxine-labeled autologus platelets following the
      recommendations of the International Committee for Standardization in
      Haematology: blood samples were taken at 30 min and 2 and 4 hr and thereafter
      daily for 7 days. PST was calculated by the weighted mean method and ranged from
      18 to 219 hr (mean value = 98). PST was also calculated using only the data
      collected at 2, 48 and 96 hr. If the radioactivity in the blood at 96 hr exceeded
      10% of the 2-hr value, the additional point at 168 hr was used. RESULTS: By using
      this reduced dataset, we obtained a correlation of r = 0.97 with the PST obtained
      from the whole dataset. In 24 patients, the difference was between +/- 10 hr and
      exceeded 1 day in only 4. CONCLUSION: About 94% of the data may be recovered with
      only three or four blood samples and the duration may be shortened to 4 days in a
      significant proportion of patients (48% of ITP patients). This approach offers
      the advantages of increased patient throughput, compliance and reduced
      examination costs.

PMID- 9189155
TI  - Lung perfusion scans and hemodynamics in acute and chronic pulmonary embolism.
AB  - To assess the relationship between pulmonary vascular obstruction and hemodynamic
      status in acute pulmonary embolism (APE) and in chronic thromboembolic pulmonary
      hypertension (CTEPH), perfusion lung scan and hemodynamic measurements were
      obtained in 31 consecutive patients with APE and in 45 with CTEPH. METHODS: Lung
      scans were scored independently by two experience observers who determined the
      percentage of vascular obstruction (PVOs). Mean pulmonary artery pressure (PAP)
      and total pulmonary resistance (TPR) were obtained during right heart
      catheterization. In patients with APE, measurements were recorded within a 1-hr
      interval before and 12 hours after thrombolysis. This yielded 62 paired PVOs
      values with concomitant PAP and TPR measurements. In patients with CTEPH, data
      were recorded within a 3-day interval. RESULTS: Mean PVOs (%) values were similar
      in APE and CTEPH patients (59 +/- 13 vs. 58 +/- 15), whereas PAP and TPR were
      significantly higher in CTEPH patients (51 +/- 17 mmHg and 23 +/- 11 U/m2,
      respectively) than in APE patients (23 +/- 8 mmHg and 9 +/- 5 U/m2, respectively,
      p < 0.001). In APE patients, significant hyperbolic correlations were found
      linking PVOs with PAP and TPR (r = 0.75, p < 0.01 for PAP; r = 0.71, p < 0.01 for
      TPR). In CTEPH, there were no significant correlations between PVOs and PAP or
      TPR. For the same level of PVOs, patients with CTEPH had higher PAP and TPR value
      than patients with APE. CONCLUSION: In APE without prior cardiopulmonary disease,
      increases in PAP and TPR are correlated in a nonlinear fashion with the degree of
      pulmonary vascular obstruction as assessed by lung scanning. In CTEPH patients,
      the higher PAP and TPR values as compared to APE patients with comparable degrees
      of PVOs are consistent with previous reports that pulmonary hypertension in CTEPH
      is due not only to the obstruction of proximal pulmonary arteries but also to
      remodeling of small distal arteries in nonoccluded areas.

PMID- 9189156
TI  - Radioiodine uptake in the chest.

PMID- 9189157
TI  - Procedure guideline for technetium-99m-HMPAO-labeled leukocyte scintigraphy for
      suspected infection/inflammation. Society of Nuclear Medicine.

PMID- 9189158
TI  - Procedure guideline for gallium scintigraphy in the evaluation of malignant
      disease. Society of Nuclear Medicine.

PMID- 9189159
TI  - Procedure guideline for gallium scintigraphy in inflammation. Society of Nuclear
      Medicine.

PMID- 9189160
TI  - Procedure guideline for indium-111-leukocyte scintigraphy for suspected
      infection/inflammation. Society of Nuclear Medicine.

PMID- 9189161
TI  - Quantification of thyroid volume.

PMID- 9189162
TI  - Functional brain imaging in 200 patients after whiplash injury.

PMID- 9189163
TI  - Where are the sugar radicals in irradiated DNA?
AB  - Numerous sugar radicals have been observed by EPR and ENDOR spectroscopy in X
      irradiated nucleosides and nucleotides. However, no sugar radicals have been
      observed in irradiated DNA. One possibility exists that sugar radicals may be
      present in relatively small abundance and therefore have so far escaped
      detection. Another possibility is that each of the five carbon-centered H
      abstraction sugar radicals may exist in a wide range of conformations. Adding
      together various groups of radicals with different hyperfine couplings and
      anisotropic g factors may result in very broad EPR lines which would be difficult
      to detect. Using the crystal structure of a B-DNA dodecamer, the conformations of
      the five H-abstraction sugar radicals have been computed at all sites. The X-band
      EPR spectra for each radical were then simulated using typical alpha-proton and
      beta-proton couplings computed from the various radical conformations. The
      results suggest considerable broadenings of the EPR lines for the C2', C3' H
      abstraction radicals. Composite EPR spectra were simulated by adding 15% of an H
      abstraction radical to the DNA spectrum. The results indicate that the outer
      lines of the C1' radical are visible and should be easy to identify. The broad
      spectra of the C2' and C3' radicals are barely visible. The simulated spectra of
      the C4' and C5' radicals are basically doublets and are obscured by the DNA
      signal.

PMID- 9189164
TI  - Caffeine-induced apoptosis reveals a persistent lesion after treatment with
      bromodeoxyuridine and ultraviolet-B light.
AB  - Ultraviolet-B (UVB) light treatment of synchronized V79 Chinese hamster cells
      after pulse-labeling with bromodeoxyuridine (BrdUrd) reveals a marked age
      response for cell killing. Incubation after treatment in growth medium containing
      caffeine increases cell killing during the resistant portions of the cell cycle,
      resulting in a much less marked age response to UVB irradiation. Examination of
      the split-dose survival curves for BrdUrd and UVB light in the presence or
      absence of caffeine indicates that sensitization by caffeine is completely
      independent of the sparing effect of dose fractionation. Further, sensitization
      by caffeine is nearly complete after the first mitosis after the UVB exposure.
      With delayed addition of caffeine, however, nearly full sensitization can be
      elicited as late as two cell cycles after the treatment with BrdUrd and UVB
      light. Also, synchronized cells exposed to caffeine after treatment with BrdUrd
      and UVB in the S phase cease to incorporate radiolabeled thymidine and undergo
      apoptosis after the second mitosis. Thus exposure to caffeine reveals a
      persistent sensitivity lasting for at least two cell cycles, after the injury
      induced by treatment with BrdUrd and UVB.

PMID- 9189165
TI  - Stem cell factor has contrasting effects in combination with 5-fluorouracil or
      total-body irradiation on frequencies of different hemopoietic cell subsets and
      engraftment of transplanted bone marrow.
AB  - The effect of stem cell factor (SCF) given at 24, 12 and 2 h before either 5
      fluorouracil (5-FU) or total-body irradiation (TBI) was investigated on a range
      of bone marrow hemopoietic cell subsets that included primitive stem cells
      capable of long-term repopulation in bone marrow transplant (BMT) recipients. At
      24 h after treatment, the femoral content of transient and permanent repopulating
      stem cell subsets was assessed from the frequency of early- and late-developing
      cobblestone area-forming cells (CAFCs) growing in stroma-associated cultures. At
      this time untreated 3 x 10(6) congenically marked donor bone marrow cells (B6-Gpi
      Ia-->B6-Gpi-Ib) were transplanted and the level of erythroid engraftment was
      followed over 1 year. Analysis of the frequencies of CAFCs in host bone marrow
      after treatment with SCF demonstrated a remarkable increase in the number of
      early-developing CAFC subsets by about 10-fold. At the same time SCF conferred a
      sensitization of these subsets after treatment with 5-FU, which indicated an
      enhanced proliferative activity. The SCF-induced increase in the number of
      progenitor cells, however, was the more dominant process in the irradiated
      animals, resulting in less overall depletion of CAFCs. These contrasting results
      provide an explanation for the sensitization by SCF of 5-FU-induced lethality and
      its converse protection against radiation-induced lethality as reported by
      others. Nevertheless, the number of the more primitive CAFC subsets appearing at
      28 and 35 days in culture and their sensitivity to 5-FU or radiation remained
      unaffected by this short SCF treatment. The number of CAFCs that remained in the
      bone marrow largely predicted the subsequent patterns of donor marrow engraftment
      in the treated BMT recipients: SCF enhanced short-term engraftment after
      treatment with 5-FU while it reduced the need for short-term engraftment after
      irradiation. Only irradiation afforded long-term engraftment through depletion of
      primitive host stem cells, and this was moderately improved by prior treatment
      with SCF.

PMID- 9189166
TI  - Simulation of measurements of uptake of 123I-iodide in the thyroid of fetal
      chimpanzees.
AB  - The quantitative assessment of the uptake of 123I-iodide (123I-) in the fetal
      thyroid in vivo was simulated in phantom measurements. First, the relationship
      between the depth of the fetal thyroid phantom and the two-peak ratio, the ratio
      of the counts in the gamma-ray and the X-ray energy windows of the registered
      spectrum, was determined. Subsequently, the attenuation of the gamma-ray signal
      in relationship to the depth of the fetal thyroid phantom was determined.
      Finally, the relationship between the two-peak ratio and the attenuation of the
      gamma-ray signal was deduced. For a reliable correlation, the signal recorded
      from the radioactivity surrounding the fetal thyroid phantom has to be subtracted
      from that obtained with the fetal thyroid phantom present. A correction curve was
      generated to be applied to the in vivo measurements. It is concluded that with
      this method determination of uptake of 123I- in the fetal thyroid is feasible.

PMID- 9189167
TI  - Protection of the maternal and fetal thyroid from radioactive contamination by
      the administration of stable iodide during pregnancy. An experimental evaluation
      in chimpanzees.
AB  - The safety and efficacy of the administration of stable iodide to protect the
      fetal thyroid from exposure to radioactive iodide were investigated in
      chimpanzees in weeks 19 to 21 of pregnancy. The mean 24-h uptake of iodide in the
      fetal thyroid, determined with 123I-, was 1.8%. Administration of stable
      potassium iodide (KI), 0.65, 1.95 or 6.5 mg per kg body weight, 1 h before tracer
      injection reduced the fetal uptake satisfactorily. Only the higher doses were
      effective after 20 h. Excess iodide may impair a child's thyroid status. However,
      adverse effects were not found during the 11 days the animals ingested these
      doses. Tracer concentrations in the amniotic fluid were 30- to 130-fold lower
      than in the urine. The dose to the fetus from radioactivity in the maternal
      bladder was estimated by computer simulation. The potential increment of the risk
      from this dose during the ingestion of stable iodide is smaller than the
      reduction of risk achieved by inhibiting the uptake of radioactive iodide by the
      fetal thyroid. The conclusion of the experiments is that stable iodide can be
      used safely and effectively to protect the fetal thyroid against contamination
      with radioactive iodine.

PMID- 9189168
TI  - Protection of the infant thyroid from radioactive contamination by the
      administration of stable iodide. An experimental evaluation in chimpanzees.
AB  - Protection of the thyroid from radioactive contamination by the administration of
      stable iodide was investigated in chimpanzees aged 2 to 98 weeks. The uptake of
      iodide in the thyroid was measured with 123I-. The animals were subjected to a
      control measurement first, and subsequently the thyroid uptake of 123I- was
      determined twice; once at the start and once at the end of 11 days of ingestion
      of 0.5, 1.5 or 5.0 mg of stable iodide per kg body weight per day. The three
      doses of iodide reduced the control thyroid iodide uptake of 10 to 30% to lower
      than 1% when ingested 1 h before exposure to the tracer and to 2-4% when ingested
      20 h before exposure. In the latter experiments 0.5 mg iodide/kg was less
      effective than doses of 1.5 mg/kg or higher. The physiological state of the
      thyroid of control infant chimpanzees does not differ from that of human infants.
      Incidentally, an increased level of TSH was found during the ingestion of iodide,
      but with unaltered thyroxine levels. Therefore, it is concluded that a daily dose
      of 1.5 mg stable iodide/kg body weight and higher offers optimal protection of
      the thyroid against exposure to radioactive iodine in infants and that, when used
      during 10 days, it leaves the thyroid unaffected.

PMID- 9189169
TI  - Radium dial workers: issues concerning dose response and modeling.
AB  - The mortality pattern of women who began employment as luminizers in the radium
      dial industry before 1930 was followed through 1990. Hazard models with time
      dependent covariates were used on mortality data either organized by individual
      death times or grouped into cross-classified person-year tables. These models
      were used to quantify trends in mortality associated with either death from or
      diagnosis of bone sarcoma or head carcinoma. The accumulation of skeletal doses
      from 226Ra and 225Ra was an important predictor of the risk of death from bone
      sarcoma. Women exposed to 226Ra at ages associated with active bone growth were
      at greater risk of bone sarcoma than women receiving even larger exposures at an
      age when their skeletons would have been fully developed. Exposure to only 226Ra
      was found to be an important predictor of risk for carcinoma of the mastoid air
      cells and paranasal sinuses. For the cranial sites, where adult dimensions are
      attained early in life, an effect of age at exposure could not be detected.

PMID- 9189170
TI  - Hyperbaric oxygen improves tumor radiation response significantly more than
      carbogen/nicotinamide.
AB  - This laboratory previously demonstrated that hyperbaric oxygen and hyperbaric
      carbogen improved oxygenation in the R3230Ac tumor, but normobaric 100% O2 and
      carbogen did not. The current study assessed tumor growth after exposure to
      radiation plus either hyperbaric oxygen, carbogen or carbogen/nicotinamide and
      the relationship between pretreatment tumor oxygenation and growth time. R3230Ac
      carcinomas were grown in the flanks of F344 rats. Animals were randomized to one
      of seven radiation treatment groups: sham irradiation or irradiation plus room
      air, hyperbaric oxygen (100% O2/3 atmospheres), nicotinamide (0.3 mg/g
      intraperitoneally 20 min before irradiation), carbogen, carbogen/nicotinamide or
      hyperbaric oxygen/nicotinamide. Tumors received 20 Gy in a single dose. Median
      growth times were 6, 18, 18, 20, 22, 28 and 27 days for controls and irradiation
      plus room air, carbogen, nicotinamide, carbogen/nicotinamide, hyperbaric oxygen
      and hyperbaric oxygen/nicotinamide, respectively. Irradiation with hyperbaric
      oxygen, hyperbaric oxygen/ nicotinamide and carbogen/nicotinamide increased
      growth time (P < 0.001, P < 0.001 and P = 0.003, respectively) relative to room
      air. Hyperbaric oxygen was significantly more effective than
      carbogen/nicotinamide (P = 0.001). Growth times for all tumors exposed to
      hyperbaric oxygen were longer than those of the most fully oxygenated tumors (no
      baseline pO2 values < 10 mm Hg) not exposed to hyperbaric oxygen (P < 0.001).
      These results suggest that hyperbaric oxygen may improve radiation response by
      additional mechanisms separate from overcoming the oxygen effect.

PMID- 9189171
TI  - Oxidation of human high-density lipoproteins by .OH and .OH/O(.-)2 free radicals.
AB  - The aim of this work was to specify the mechanisms involved in the radical
      oxidation of human high-density lipoprotein (HDL) and to compare these mechanisms
      with those described previously for the oxidation of low-density lipoprotein
      (LDL) under the same experimental conditions (Bonnefont-Rousselot et al., Radiat,
      Res. 134, 271-282, 1993). The oxidation of HDL, initiated by .OH or .OH/O(.-)2
      free radicals from gamma radiolysis of water, was evaluated as a function of
      increasing radiation dose by analyzing quantitatively the decrease of endogenous
      alpha-tocopherol and the formation of oxidation products (thiobarbituric acid
      reactive substances and conjugated dienes). All qualitative conclusions were
      supported by quantitative data (radiation yields and concentrations of the
      oxidation markers at high radiation doses) and by the mechanisms of the kinetics,
      .OH free radicals in the absence of oxygen were less efficient in initiating HDL
      oxidation than in the presence of oxygen (action of .OH/O(.-)2 free radicals),
      which was in agreement with the enhancement of the action of .OH free radicals by
      oxygen. The remaining significant level of vitamin E in HDLs at high radiation
      doses in the absence of oxygen could be explained by a regeneration of vitamin E
      by an oxidation product that was able to reduce the alpha-tocopheroxyl radical.
      The yields related to the decrease in the vitamin E content of HDLs after
      exposure to radiation with .OH or .OH/O(.-)2 free radicals were slightly higher
      than those obtained previously in LDLs under similar experimental conditions.
      Moreover, in the presence of oxygen, .OH free radicals led to a lower formation
      of thiobarbituric acid-reactive substances in HDLs than in LDLs. Such
      discrepancies in the behavior of these two lipoprotein fractions could be related
      to the differences in the chemical composition of HDLs and LDLs.

PMID- 9189172
TI  - Transient increase in glycolytic metabolism in cultured tumor cells immediately
      after exposure to ionizing radiation: from gene expression to deoxyglucose
      uptake.
AB  - The transient change in uptake of deoxyglucose (DG) and expression of glycolysis
      associated gene products in cultured tumor cells (LS180 human colon
      adenocarcinoma cells) immediately after single-dose X irradiation were examined
      to acquire basic data for use in the early assessment of tumor responses to
      radiation treatment by position emission tomography. An increase in accumulation
      of DG was found 3-5 h postirradiation. Inhibitors of both mRNA and protein
      synthesis and glycoprotein transport suppressed the increase in accumulation of
      DG to the control level. Both the glucose transporter-1 mRNA expression and the
      enzymatic activity of hexokinase in the cells were significantly elevated in
      conjunction with high DG accumulation. These findings indicate that the
      transiently elevated glucose metabolism occurred via processes at the levels of
      gene expression. These transient tumor cell responses might be useful for the
      early assessment of radiation damage.

PMID- 9189173
TI  - The embryonic and fetal effects in ICR mice irradiated in the various stages of
      the preimplantation period.
AB  - Pregnant ICR mice were irradiated with 0.1-2.5 Gy 137Cs gamma rays at a dose rate
      of 0.2 Gy/min at 2, 48, 72 or 96 h postconception. In the mice irradiated during
      these stages of preimplantation, embryonic/fetal mortalities, incidence of
      external gross malformations, fetal body weight and sex ratio were observed at
      day 18 of gestation. There were significant increases in death in the
      preimplantation period compared to control levels after exposure to at least 0.25
      Gy at 2 and 72 h postconception and 0.5 Gy at 96 h postconception. In contrast, a
      dose of 1.5 Gy was required at 48 h postconception. The frequency of embryonic
      death was analyzed using a logistic regression for comparing among stages. These
      analyses demonstrated that the regression slopes were significantly positive for
      groups in all stages and increased with decreasing time after conception.
      Furthermore, the regression analyses suggested that the most sensitive stage for
      preimplantation death and embryonic death was 2 h postconception, when embryos
      consisted of one cell. Many types of external gross malformations, such as
      exencephaly, cleft palate and anophthalmia, were observed even in the mice
      irradiated with 0.1 Gy at 2, 72 and 96 h postconception. In the same manner as
      embryonic mortality, the regression analyses suggested that the susceptibility of
      the mice irradiated at 2, 72 and 96 h postconception during preimplantation to
      external malformations was higher than that of the mice irradiated at 8 or 11
      days of gestation, which is the period of organogenesis, and that the most
      sensitive stage for external malformations was 2 h postconception. However, no
      malformations were observed in the mice irradiated at 48 h postconception when
      the embryos were precompacted with four to eight cells.

PMID- 9189174
TI  - Effect of ondansetron and ICS 205-930 on radiation-induced hypothermia in rats.
AB  - This study determined the effects of the 5-hydroxytryptamine (5-HT) serotonin
      antagonists ondansetron and (3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester
      HCl (ICS 205-930) on hypothermia induced in rats by irradiation and by
      administration of a 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-Me-5
      HT). Intraperitoneal (i.p.) administration of 50-200 micrograms/kg of ondansetron
      and intraventricular administration of 5-20 micrograms of ondansetron attenuated
      hypothermia induced by 20 Gy gamma rays. However, the same doses of ondansetron
      administered i.p. or intraventricularly did not antagonize the hypothermia
      induced by 10 micrograms 2-Me-5-HT. In contrast, i.p. administration of 50-200
      micrograms/kg of ICS 205-930 and intraventricular administration of 5-20
      micrograms of ICS 205-930 attenuated hypothermia induced by radiation and 2-Me-5
      HT. These results indicate that ICS 205-930 attenuates hypothermia induced by
      radiation and 2-Me-5-HT. However, the doses of ondansetron that attenuated
      radiation-induced hypothermia did not attenuate hypothermia induced by 2-Me-5-HT.

PMID- 9189175
TI  - Glycophorin A as a biological dosimeter for radiation dose to the bone marrow
      from iodine-131.
AB  - The frequency of peripheral blood erythrocyte variants exhibiting allelic loss of
      glycophorin A (N/M antigen) has been used previously as a biological dosimeter to
      assess somatic mutations in bone marrow cells from external whole-body
      irradiation. The aim of the present study was to determine whether this marker
      could be used as a measure of bone marrow genotoxicity induced by 131I in the
      treatment of thyroid cancer. Flow cytometry of immunolabeled erythrocytes was
      performed to enumerate glycophorin A variants before and after eight therapy
      doses of 131I administered to five patients with differentiated thyroid
      carcinoma. Bone marrow radiation exposure from each dose was calculated from the
      integrated retention of 131I in the whole body and in the blood. In addition, the
      accumulated dose to the bone marrow received from earlier 131I therapy was
      calculated for each patient. Regression analysis was performed on the frequency
      of two glycophorin A variant cell types (N/O and N/N) as a function of
      accumulated dose to the bone marrow. Frequency of N/O variant cells showed a
      significant dose-related increase with a slope of 10.9 x 10(-6) per sievert. This
      dose effect is about one-half that previously observed after whole-body external
      irradiation at high dose rate. This decreased response could be explained by the
      low dose rate of the radiation to the bone marrow from 131I.

PMID- 9189176
TI  - Prevalence of uterine myoma detected by ultrasound examination in the atomic bomb
      survivors.
AB  - Benign tumors of several organs have been demonstrated to occur as late effects
      of atomic bomb exposure, and a recent addition to the list of affected organs is
      the uterus. The increased incidence of uterine myoma noted in Radiation Effects
      Research Foundation (RERF) Adult Health Study Report 7 (Wong et al., Radiat, Res.
      135, 418-430, 1993), however, was based on self-reported information, optional
      gynecological examination and patient-requested ultrasound examination. Thus the
      possibility of dose-related bias in case detection was a serious concern.
      Therefore, the relationship between the prevalence of uterine myoma and dose to
      the uterus was examined after excluding as much bias as possible by asking all
      women who had undergone biennial examinations from December 1991 through December
      1993 to undergo ultrasound examinations. Among 2506 female participants in
      Hiroshima, the uterus was visualized by ultrasound examination in 1190, and 238
      were found to have uterine nodules. Multiple logistic analysis using Dosimetry
      System 1986 uterine doses revealed a significant dose response for the prevalence
      of uterine nodules. The odds ratio at 1 Gy was 1.61 (95% confidence interval:
      1.12-2.31). It is unlikely that the observed relationship after adjusting for
      bladder filling, volume of the uterus, age and menopause status was the result of
      dose-related bias. These results support previous findings at RERF and provide
      further evidence that radiation exposure is one of the factors associated with
      uterine myoma.

PMID- 9189177
TI  - Twelfth annual Mallinckrodt institute of radiology-radiation oncology center
      symposium for radiation and biological sciences.

PMID- 9189178
TI  - Gestational trophoblastic diseases and their treatment.

PMID- 9189179
TI  - The treatment of disseminated malignant melanoma with special reference to the
      role of interferons, vinca alkaloids and tamoxifen.
AB  - Malignant melanoma continues to increase in incidence. While early melanoma is
      highly curable by surgical means, the prognosis of patients with more advanced
      lesions and/or metastatic disease remains poor. Conventional chemotherapy with
      dacarbazine has a low frequency and short duration of response. Alternative drugs
      with single-agent activity include vinca alkaloids, nitrosoureas, procarbazine
      and platinum compounds. The addition of tamoxifen to chemotherapy, particularly
      cisplatin-based chemotherapy, appears to be beneficial. Recent studies suggest
      that combination chemotherapy may give better outcomes than single-agent
      treatment. Significant clinical activity has also been demonstrated with the use
      of interferons, particularly interferon alpha, and also with IL-2. Two recent
      studies suggest that the addition of interferon to chemotherapy may be
      beneficial. In addition, specific active immunotherapy with tumour vaccines has
      shown promise. The optimal methods of combining these treatment methods, such as
      chemotherapy and biological response modifiers/immunotherapy, however, remain to
      be defined.

PMID- 9189180
TI  - Temozolomide: a review of its discovery, chemical properties, pre-clinical
      development and clinical trials.

PMID- 9189181
TI  - Defibrillation and public expectation.

PMID- 9189182
TI  - Utstein: proactively improving the quality of cardiac arrest research.

PMID- 9189183
TI  - Repeat visits by elder emergency department patients: sentinel events.

PMID- 9189184
TI  - Who gets bystander cardiopulmonary resuscitation in a witnessed arrest?
AB  - OBJECTIVE: To identify characteristics associated with provision of bystander CPR
      in witnessed out-of-hospital cardiac arrest cases. METHODS: An observational,
      prospective, cohort study was performed using cardiac arrest cases as identified
      by emergency medical services (EMS) agencies in Oakland County. MI, from July 1,
      1989, to December 31, 1993. All patients who sustained a witnessed arrest prior
      to arrival of EMS personnel were reviewed. RESULTS: Of the 927 patients meeting
      entry criteria, the 229 patients receiving bystander CPR were younger: 60.9 +/-
      14.7 vs 67.9 +/- 14.7 years (p < 0.01). Most (76.6%) cardiac arrests occurred in
      the home. In a multivariate logistic model, only the location of arrest outside
      the home was a significant predictor of receiving bystander CPR [odds ratio (OR)
      3.8; 99% CI 2.5, 5.9]. Arrests outside the home were associated with
      significantly improved outcome, with 18.2% of out-of-home and 8.2% of in-home
      victims discharged from the hospital alive (OR 2.5; 99% CI 1.4, 4.4). CONCLUSION:
      Patients who have had witnessed cardiac arrests outside the home are nearly 4
      times more likely to receive bystander CPR, and are twice as likely to survive.
      This observation emphasizes the need for CPR training of family members in the
      authors' locale. This phenomenon may also represent a significant confounder in
      studies of out-of-hospital cardiac arrest and resuscitation.

PMID- 9189185
TI  - The effect of hypertonic sodium and dantrolene on propranolol cardiotoxicity.
AB  - OBJECTIVE: To evaluate whether measures that lower cytosolic calcium (Ca) can
      reverse propranolol (PROP) toxicity in the isolated, perfused rat heart. METHODS:
      Isolated rat hearts were perfused on a Langendorff apparatus with Krebs-Henseleit
      bicarbonate (KHB) buffer solution. Toxicity was produced by perfusing the hearts
      with PROP (5 micrograms/mL) for 30 minutes. Subsequently, the hearts were treated
      for 30 minutes with buffer containing PROP plus experimental treatment. Three
      treatments were chosen: hypertonic sodium (Na) (160 mmol), to stimulate Na-Ca
      exchange, dantrolene (DAN) (10 mumol), to inhibit Ca release from sarcoplasmic
      reticulum, and combined hypertonic Na and DAN. The hearts were paced after 20
      minutes of treatment. Heart rate (HR), left ventricular peak systolic pressure
      (LVP), the first derivative of LVP (dP/dt), and coronary flow were measured.
      RESULTS: PROP decreased HR and rendered the hearts refractory to pacing. PROP did
      not alter dP/dt. PROP increased LVP consistent with increased cytosolic Ca.
      Combined hypertonic Na and DAN treatment restored the ability to pace PROP-toxic
      hearts to the basal HR. Individually, hypertonic Na or DAN treatment partially
      restored the ability to pace toxic hearts. As experimental treatments increased
      HR, dP/dt and LVP decreased, consistent with decreased cytosolic Ca availability.
      CONCLUSION: These data are consistent with the hypothesis that bradycardia during
      beta-blocker cardiotoxicity is mediated by altered Ca homeostasis.

PMID- 9189186
TI  - Population density, automated external defibrillator use, and survival in rural
      cardiac arrest.
AB  - OBJECTIVE: To determine whether population density is an independent predictor of
      survival from out-of-hospital cardiac arrest managed by basic life support (BLS)
      services using automated external defibrillators (AEDs). METHODS: A
      retrospective, observational study in Kentucky of 34 BLS services covering 22
      counties during the years 1992 to 1994 who used AEDs to treat patients who had
      out-of-hospital cardiac arrests. RESULTS: Of 311 patients who had out-of-hospital
      cardiac arrests, 110 (35%) were defibrillated, 46 (15%) were resuscitated to
      hospital admission, and 19 (6%) survived to hospital discharge. Univariate
      predictors for survival to hospital discharge were emergency medical services
      response interval (from call receipt to ambulance arrival) < 8 minutes,
      defibrillation by the AED, initial rhythm of ventricular fibrillation or
      ventricular tachycardia (VF/VT), and population density > 100/square mile (sq mi)
      for the BLS service area (p < 0.001). A forced logistic regression model of
      survival to hospital discharge, using these 4 factors plus the presence of a
      witnessed arrest or bystander CPR, demonstrated that population density > 100/sq
      mi was highly significant (OR 9.4, 95% CI: 1.7 to 51.4, p < 0.01). Stepwise
      logistic regression models with combinations of these 6 factors found that
      survival to hospital discharge was best predicted by an initial rhythm of VF/VT
      (p = 0.004) and population density > 100/sq mi (p = 0.011). CONCLUSIONS:
      Population density is strongly associated with survival from out-of-hospital
      cardiac arrest. BLS services within areas with population densities < or = 100/sq
      mi sustained little benefit from the addition of AEDs to their treatment of
      patients who had out-of-hospital cardiac arrests.

PMID- 9189187
TI  - Calcium, magnesium, and phosphorus: emergency department testing yield.
AB  - OBJECTIVES: To investigate how often the ED ordering of stat serum calcium
      (Ca+2), magnesium (Mg+2), and phosphorus (PO4(-3)) levels affected clinical
      treatment; to define the diagnoses of patients for whom Ca+2, Mg+2, and PO4(-3)
      measurements did affect clinical therapy; and to suggest guidelines for more
      appropriate ordering of these laboratory tests. METHODS: A retrospective chart
      review was performed in an academic teaching hospital. All adult ED patients who
      had Ca+2, Mg+2, or PO4(-3) laboratory testing during the 9-month study period
      were included and evaluated for potential clinical impact of an abnormal Ca+2,
      Mg+2, or PO4(-3) laboratory test. RESULTS: 1.477 patients had Ca+2, Mg+2, or PO4(
      3) measured while in the ED during the study period. Of these, 260 patients
      (17.6%) had a total of 312 abnormal Ca+2, Mg+2, or PO4(-3) values as defined by
      results exceeding +/- 15% of normal reference values. Of these, only 5 patients
      (0.3%) received treatment for abnormal values in the ED, while 75 patients (5.1%)
      were treated once admitted to the hospital. In this study, the only diagnostic
      groups to whom significant treatment was administered were diabetic patients
      (Ca+2 and PO4(-3); alcoholic patients (Mg+2); and renal failure patients (Ca+2,
      Mg+2, and PO4(-3). CONCLUSION: These results suggest that stat Ca+2, Mg+2, and
      PO4(-3) levels seldom affect clinical treatment in the ED. The frequency of
      ordering these tests may be reduced by obtaining Ca+2, Mg+2, or PO4(-3)
      measurements only for patients known to be at risk for such abnormalities, based
      on their existing or suspected diagnoses. The authors suggest obtaining these
      tests, when indicated, on a "non-stat" basis, with the subsequent laboratory
      results becoming available in-hospital, where treatment is more likely to occur.

PMID- 9189188
TI  - Out-of-hospital experience with the syringe esophageal detector device.
AB  - OBJECTIVE: To determine the accuracy of a syringe esophageal detector device
      (EDD) for detecting esophageal intubations in an out-of-hospital setting.
      METHODS: Prospective, observational study of adult (age > or = 18 years) patients
      intubated by paramedics from October 1993 through May 1994 in an urban emergency
      medical services (EMS) system. Paramedics were instructed to record the EDD
      reading after endotracheal tube placement. However, paramedics were instructed
      not to modify their tube locations based on the EDD reading. Tube placement was
      evaluated by a physician upon patient arrival at a local ED. RESULTS: Paramedics
      performed 374 intubations during the study period, and in 213, the EDD was used.
      Of these 213 patients, 45 were excluded from analysis (32-tube placement not
      confirmed, 11-paramedic uncertain of EDD reading, 2-too young). In the remaining
      168 intubations, the EDD correctly identified 5 of 10 esophageal intubations
      (sensitivity 50%; 95% CI: 19%, 81%). The EDD correctly identified 156 of 158
      tracheal intubations (specificity 99%; 95% CI: 96%, 100%). CONCLUSIONS: In this
      paramedic field study, the EDD demonstrated poor sensitivity for esophageal
      intubations. Further EMS studies of the EDD are needed to clarify the value of
      the device in out-of-hospital emergent clinical intubations.

PMID- 9189189
TI  - Bioimpedance cardiac output measurements in patients with presumed congestive
      heart failure.
AB  - OBJECTIVE: To describe preliminary ED experience with thoracic electrical
      bioimpedance (TEB) for evaluation of patients with complaints suggestive of
      congestive heart failure (CHF). METHODS: A 6-month, prospective, observational
      study was performed using a convenience sample of patients with signs and
      symptoms consistent with CHF. Patients were excluded if they had received
      medication prior to arrival in the ED, if they were obese, and if they had
      unstable vital signs. They also were excluded if they were combative, refused to
      sign consent, or had invasive lines that did not allow for TEB lead placement.
      Patients also were excluded if the study could not be completed because the
      patient was taken from the department for a diagnostic test, or if there were no
      good follow-up records available 6-12 months after the patient's visit. The
      patient's physician was blinded to the output of the TEB monitor. Cardiac output
      (CO), stroke volume (SV), end-diastolic volume (EDV), thoracic fluid index (TFI),
      and acceleration index (ACI) were recorded at 5-minute intervals. Results were
      evaluated for the time intervals 0-5 minutes, 30-35 minutes, and 60-65 minutes.
      RESULTS: Seven patients were included in the study. The echocardiographic
      diagnoses were hypertrophic cardiomyopathy (2 cases), dilated cardiomyopathy (2
      cases), ischemic cardiomyopathy (1 case), right ventricular hypertrophy (1 case),
      and pericardial effusion (1 case). Significant changes were seen in all cardiac
      parameters, with variance from individual to individual. CONCLUSIONS: Significant
      differences in TEB variables exist between patients who appear similar on initial
      examination in the ED. Changes noted on TEB may help to further elucidate
      physiologic differences. The clinical use of TEB-based hemodynamic measurements
      to guide presumed CHF patient management remains speculative.

PMID- 9189190
TI  - Frequent users of the emergency department: can we intervene?
AB  - OBJECTIVE: To determine whether the use of individualized patient care plans and
      multidisciplinary case management would decrease ED utilization by frequent ED
      users. METHODS: The authors performed a prospective, randomized clinical trial of
      the impact of a care plan on ED use by adults with frequent ED visits. Patients
      with > 10 ED visits to a university hospital in 1993 were identified. Patients
      were matched for age, sex, and number of visits and then randomized into 2
      groups. The control group received standard emergency care. The treatment group
      was managed by a multidisciplinary team and treated in the ED according to
      individualized care plans. ED use was tracked at the university hospital and at
      the other 5 community hospitals in the city. RESULTS: Of the 70 enrolled
      patients, 25 of 37 control patients and 27 of 33 treatment patients made visits
      to the university hospital during the 1-year study period. Only those patients
      with follow-up visits were included in the data analysis. Patients remaining in
      the control group made 247 total visits (range 1-65) to the university hospital
      and 179 total visits (range 0-38) to the community hospitals during the study
      period. Patients in the treatment group made 320 total visits (range 1-72) to the
      university hospital and 254 total visits (range 0-135) to the community hospitals
      during the study period. There was no significant difference in the median number
      of visits made to either the university hospital or the community hospitals by
      the patients in the control group and those in the treatment group. CONCLUSIONS:
      The use of individualized care plans and case management did not significantly
      decrease ED utilization by frequent ED users. However, the impact of
      individualized care plans and case management on other quality-of-care measures
      (e.g., patient satisfaction, ED length of stay, hospitalizations, primary care
      visits, and health care costs) remains to be determined.

PMID- 9189191
TI  - Predictors of repeat emergency department visits by elders.
AB  - OBJECTIVE: To determine which characteristics of older patients who use a
      hospital ED are associated with repeat visits during the 90 days following the
      index visit. METHODS: The study was conducted in the ED of a 400-bed university
      affiliated acute care community hospital in Montreal. Patients aged > or = 75
      years who visited the ED between 08:00 and and 16:00 on a convenience sample of
      days over an 8-week period (July and August 1994) were assessed using a
      questionnaire, physical and cognitive status instruments, and a functional
      problem checklist. The hospital's administrative database was used to identify
      repeat visits during the 90 days following the ED visit. The representativeness
      of the sample was assessed by analyses of ED visits made by 4,466 persons aged >
      or = 65 years during a 12-month period (September 1993 to August 1994) using the
      hospital's administrative database. RESULTS: 256 patients aged > or = 75 years
      visited the ED during the study period and 167 were assessed. Of these, 54 (32%)
      were admitted to the hospital. Among the 113 patients released from the ED, 27
      (24%) made repeat visits during the next 90 days. In univariate analyses, repeat
      visits were significantly associated with the number of functional problems,
      cognitive impairment, and previous ED visits. In multiple logistic regression,
      male gender, living alone, and number of functional problems were independent
      predictors of repeat visits. In the administrative data analyses, nighttime
      arrival to the ED for the index visit was significantly associated with repeat
      visits. CONCLUSIONS: Self-reported risk factors can help to identify a group of
      elders likely to make repeated ED visits; the development of a screening
      instrument incorporating questions on these problems and implementation of
      appropriate interventions might improve these patients' quality of life and
      reduce the demand for further ED care in this age group.

PMID- 9189192
TI  - Psychosocial difficulties and emergency department use.
AB  - OBJECTIVE: To determine whether psychosocial difficulties are more prevalent
      among ambulatory patients using the ED for nonemergent complaints as compared
      with ambulatory patients having emergent complaints. METHODS: A survey of
      noncritical ED patients was performed using anonymous questionnaires addressing
      psychosocial difficulties: psychiatric illness, educational level, homelessness,
      alcohol and/or drug dependency (CAGE and DAST surveys), and depression (DSM-III
      criteria). Three independent physicians ranked each patient's chief complaint as
      either emergent or appropriate for primary care. The majority ranking was used to
      determine whether the complaint was emergent. Groups with and without specific
      psychosocial difficulties were compared for their proportion of emergent vs
      primary care complaints. RESULTS: Of 700 patients, 367 (52%) met criteria for >
      or = 1 psychosocial difficulty [acute psychosis-36 (5%), illiteracy-139 (20%),
      homelessness-45 (6%), alcohol dependency-111 (16%), drug dependency-66 (9%), and
      depression-130 (19%)]. There were 379 (54%) ED visits considered emergent.
      Patient groups with vs without > or = 1 psychosocial difficulty had similar rates
      of emergent visits (58% vs 50%, p = 0.04). Emergent visit rates also were similar
      for subgroups with vs without specific psychosocial difficulties: psychosis (56%
      vs 54%, p = 1.00) illiteracy (58% vs 53%, p = 0.89), homelessness (62% vs 54%, p
      = 0.33), alcohol dependency (62% vs 53%, p = 0.08), drug dependency (59% vs 54%,
      p = 0.47), or depression (58% vs 53%, p = 0.42). CONCLUSION: Psychosocial
      difficulties are common among ED patients; however, emergent complaints are just
      as common in these patients as they are in those without psychosocial
      difficulties.

PMID- 9189193
TI  - SAEM Kennedy Lecture--infinite needs, finite resources: the new world of health
      care.

PMID- 9189194
TI  - Recommended guidelines for reviewing, reporting, and conducting research on in
      hospital resuscitation: the in-hospital "Utstein style". A statement for health
      care professionals from the American Heart Association, the European
      Resuscitation Council, the Heart and Stroke Foundation of Canada, the Australian
      Resuscitation Council, and the Resuscitation Councils of Southern Africa.

PMID- 9189195
TI  - Core Content for emergency medicine. Task Force on the Core Content for Emergency
      Medicine Revision.

PMID- 9189196
TI  - Prospective validation of out-of-hospital spinal clearance criteria: a
      preliminary report.

PMID- 9189197
TI  - Prescreening entire mammograms for masses with artificial neural networks:
      preliminary results.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the feasibility of combining
      wavelet transform and artificial neural network (ANN) technologies to prescreen
      mammograms for masses. METHODS AND MATERIALS: Fifty-five mammograms (29 with
      masses and 26 without) were digitized to 100-mm resolution and processed by using
      wavelet transformation. These wavelets were subjected to a linear output
      sequential recursive auto-associative memory ANN and cluster analysis with
      feature vector formation. These vectors were used in two separate experiments-one
      with 13 cases and another with seven cases held out in a test set-to train feed
      forward ANNs to detect the mammograms with a mass. The experiments were repeated
      with rerandomization of the data, four and six times, respectively. RESULTS:
      There was a statistically significant correlation (P < .01) between the network's
      prediction of a mass and the presence of a mass. With majority voting, the feed
      forward ANNs detected masses with 79% sensitivity and 50% specificity.
      CONCLUSION: Although preliminary, the combination of wavelet transform and ANN is
      promising and may provide a viable method to prescreen mammograms for masses with
      high sensitivity and reasonable specificity.

PMID- 9189198
TI  - Computer-aided detection of clustered microcalcifications on digitized
      mammograms: a robustness experiment.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the performance of an existing
      computer-aided diagnosis (CAD) scheme for the detection of clustered
      microcalcifications in a large image database. METHODS: A previously developed,
      rule-based system was used to assess detectability of microcalcification clusters
      in a set of 386 digitized mammograms with 239 verified clusters visible on 191
      images. The test was performed without any reoptimization of the scheme. None of
      the 386 images had been used in any previous scheme development or testing
      procedures. RESULTS: The CAD scheme achieved 89.5% sensitivity at an average
      false-positive detection rate of 0.39 per image. In 75% of all images, no false
      positive findings occurred. Twenty-three of 25 false-negative findings (misses)
      occurred during the last two stages in the detection process. CONCLUSION: This
      scheme produced reasonable results in a large data set of images with a large
      variety of cluster characteristics.

PMID- 9189200
TI  - Experimental correlation between T2* and ultimate compressive strength in lumbar
      porcine vertebrae.
AB  - RATIONALE AND OBJECTIVES: The authors used magnetic resonance (MR) imaging to
      investigate the correlation between T2* measurements of trabecular bone and the
      ultimate compressive strength of lumbar porcine vertebrae. METHODS: Five pigs
      that weighted 25-32 kg were sacrificed and imaged with a 1.5-T MR system. T2* of
      the lumbar vertebrae was measured from gradient-echo images. The vertebrae were
      individually compressed at a fixed speed in the direction of the spine until
      crushed. The maximum load a vertebra could resist was recorded. RESULTS: T2*
      ranged from 7.1 to 14.5 msec. T2* determined from 5-mm coronal sections differed
      from that determined from axial and sagittal sections (P < .05). Between 2.9 and
      5.4 kN of force (296-550 kg) was needed to crush a vertebra. A linear correlation
      between the ultimate compressive strength and T2* of all vertebrae was observed
      for all imaging planes and section thicknesses (P < .001, except for 10-mm
      sagittal images, for which P < .002). The T2* determined for the axial plane
      showed the best correlation with the ultimate compressive strength (r = -0.83).
      CONCLUSION: The correlation between T2* values and vertebral strength indicates
      that MR imaging may potentially be used to predict fracture risks in patients.

PMID- 9189199
TI  - Surveillance mammography and stereotactic core breast biopsy for probably benign
      lesions: a cost comparison analysis.
AB  - RATIONALE AND OBJECTIVES: The authors compared the economic effect of
      stereotactic core needle biopsy (CNB) with that of short-term unilateral
      surveillance mammography in the management of probably benign breast lesions
      detected during routine screening mammography. METHODS: Published data with
      regard to the cost of stereotactic CNB and unilateral mammography were applied to
      3,184 patients who underwent surveillance mammography; including 161 patients who
      underwent biopsy. Costs of immediate tissue diagnosis were compared with costs of
      surveillance with use of ratios of published reimbursement scales to minimize
      geographic variations. Sensitivity analyses were applied to this ratio. RESULTS:
      The cost of managing probably benign breast lesions with surveillance mammography
      was $3,307,575 less than if all lesions had been managed with CNB. The ratio of
      the cost of CNB to the cost of surveillance mammography was 8:1. This ratio is
      more sensitive to the frequency of use of CNB than to reimbursement schedules.
      CONCLUSION: With similar false-negative rates, CNB is more costly than
      surveillance and has a negative effect in the management of probably benign
      breast lesions, unless interval change during surveillance prompts tissue
      diagnosis.

PMID- 9189201
TI  - Quantitation of T2 lesion load in multiple sclerosis with magnetic resonance
      imaging: a pilot study of a probabilistic neural network approach.
AB  - RATIONALE AND OBJECTIVES: To quantitate multiple sclerosis (MS) lesions in the
      brain by using computerized techniques. METHODS: MS lesions from five patients
      were quantitated with magnetic resonance (MR) imaging by using three approaches:
      a probabilistic neural network (PNN) approach, a semiautomated method that uses a
      bifeature space approach with operator intervention at each section, and the
      "gold standard" of manual outlining of lesions. Each patient underwent two MR
      studies in 1 day. RESULTS: The PNN approach allows reasonable quantitation of
      large data sets with minimal operator input. The mean intraobserver error for the
      PNN approach was competitive with the more time-consuming bifeature space
      approach (5.2% vs 4.4%, respectively). On average, both computer assisted methods
      performed better than the manual method (mean intraobserver error, 10.1%).
      CONCLUSION: The agreement between the two computerized quantitation approaches
      was good. The number of interactive steps was substantially reduced with the PNN
      technique, leading to minimal operator intervention time.

PMID- 9189202
TI  - Two-dimensional aortographic coronary arteriography with above-K-edge
      monochromatic synchrotron radiation.
AB  - RATIONALE AND OBJECTIVES: The diagnostic potential of two-dimensional
      aortographic coronary arteriography with synchrotron radiation was examined in
      dogs. METHODS: The experiment was performed at a wiggler beam line by using a
      silicon monocrystal, fluorescent plate, and avalanche-type camera. The x-ray
      energy was adjusted to just above the iodine K-edge to obtain the highest
      contrast. Quantitative densitometry was used to compare intravenous coronary
      arteriography with aortographic coronary arteriography. RESULTS: Aortographic
      coronary arteriography clearly depicted the branches of the coronary arteries
      such as the left anterior descending coronary artery, circumferential coronary
      artery, and right coronary artery to sizes of less than 0.2 mm without major
      overlap of coronary arteries. Intravenous coronary arteriography depicted only
      the branches of the left anterior descending coronary artery and right coronary
      artery with poor image quality. The ratio of contrast material dilution was about
      2.4 to 3.4 in aortographic procedures, whereas in intravenous procedures it
      ranged widely from 7.7 to 15.6. CONCLUSION: These preliminary investigations
      indicate that two-dimensional aortographic coronary arteriography with
      synchrotron radiation promises to be a minimally invasive and easily repeatable
      method of clearly imaging the coronary arteries.

PMID- 9189203
TI  - A case study of the decision in Denmark to restrict use of high-osmolar contrast
      media in intravascular radiographic procedures.

PMID- 9189204
TI  - Report of the Department of Defense, National Cancer Institute, Department of
      Health and Human Services Office of Women's Health workshop on the mobile breast
      care center.

PMID- 9189205
TI  - Skeletal muscle mass in an asymptomatic male.

PMID- 9189206
TI  - Continuing teaching education: its time has come.

PMID- 9189207
TI  - Uptake of interventions to reduce mother-to-child transmission of HIV in the
      United Kingdom and Ireland.
AB  - OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child
      transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV
      infection in pregnancy and childhood; telephone interview with key professionals
      in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women
      and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in
      breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy.
      RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV
      infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed
      after delivery. Since 1994, zidovudine use has increased in each 6-month period
      (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the
      policy of only 48% of London maternity units to offer zidovudine to HIV-infected
      women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean
      section. Since 1990, 20% of women first diagnosed in pregnancy were reported to
      have their pregnancy terminated. CONCLUSIONS: Although detection of previously
      undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and
      particularly in London, HIV-infected pregnant women who are aware of their status
      are increasingly active in taking up interventions to reduce transmission to
      their infants. If all HIV-infected women attending for antenatal care in London
      consented to testing and took up interventions and termination of pregnancy at
      the rates observed in this study, the number of vertically infected babies born
      in London each year could be reduced from an estimated 41 to 13.

PMID- 9189208
TI  - HIV/AIDS and its risk factors in Pakistan.

PMID- 9189209
TI  - Germinal centre CD4+ T cells are an important site of HIV replication in vivo.
AB  - OBJECTIVE: CD4+ T cells are the main target for HIV. However, the highest HIV
      antigen concentration in infected subjects accumulates on the cell surface of
      follicular dendritic cells in the germinal centres of the lymphoid tissue.
      Germinal centres contain a T-helper cell subset which expresses CD57 molecules.
      Here we analysed virus replication and viral load in CD57+CD4+ germinal centre T
      cells and in the CD4+ T cells found mostly outside germinal centres (CD57-CD4+).
      METHODS: Peripheral blood mononuclear cells and lymph-node cells were prepared,
      stained for CD4 and CD57 and purified by FACS. Defined cell numbers of CD4+CD57+
      cells and CD4+CD57- cells were sorted directly into polymerase chain reaction
      (PCR) tubes by FACS, equipped with an automated cell deposition unit and analysed
      by PCR to detect proviral DNA. Based on Poisson distribution, the expected level
      of infection was calculated. Viral replication was determined by amplifying
      double-spliced, single-spliced, and full-length transcripts of HIV using serially
      diluted cDNA of the FACS-sorted cells. RESULTS: An up to 10-fold higher frequency
      of infected cells was found in the CD57+CD4+ germinal centre T cells compared
      with CD57-CD4+ T cells. Furthermore, active viral replication was detected almost
      exclusively in the CD57+CD4+ T cells. CONCLUSIONS: The CD57+CD4+ germinal centre
      T cells are one of the sites of HIV infection and replication that may play a
      pivotal role in the pathogenesis of HIV infection.

PMID- 9189210
TI  - Subtype-specific problems with quantification of plasma HIV-1 RNA.
AB  - OBJECTIVE: To determine whether two commercial assays for quantification of
      plasma HIV-1 RNA levels detect different genetic subtypes of HIV-1 with equal
      efficiency. DESIGN: Blind testing of stored plasma samples from 95 individuals
      infected with different genetic subtypes of HIV-1 (27 subtype A, 24 B, 18 C, 18
      D, two E, two G, two H, and two J). The HIV-1 subtype had previously been
      determined by direct sequencing of the V3 domain of the env gene. METHODS: One
      plasma sample from each individual was tested once by the Roche HIV monitor assay
      and once by the Organon nucleic acid sequence-based amplification (NASBA) HIV-1
      RNA quantitative assay, according to the manufacturers' recommendations.
      Information about CD4+ lymphocyte counts and antiretroviral treatment was
      available. RESULTS: The results from the two assays were strongly correlated with
      each other for subtypes B, C and D, but not for subtype A because many samples
      had RNA levels close to or below the lower detection limit of the assays. Thus,
      15 out of 27 (56%) subtype A samples were negative by the HIV monitor assay and
      12 (44%) were negative by the NASBA assay. These frequently occurring negative
      results among subtype-A-infected individuals were not due to better immunological
      status, more aggressive antiretroviral treatment, or differences in sample
      storage conditions. CONCLUSIONS: The HIV monitor assay and, possibly to slightly
      lesser degree, the NASBA assay appear unable to accurately quantify HIV-1 RNA
      levels in plasma samples from many subtype-A-infected individuals. These problems
      are likely to be due to primer mismatches and they limit the possibility of using
      these assays for routine monitoring of HIV-1-infected individuals in many parts
      of the world.

PMID- 9189211
TI  - A case of ganciclovir-resistant cytomegalovirus (CMV) retinitis in a patient with
      AIDS: longitudinal molecular analysis of the CMV viral load and viral mutations
      in blood compartments.
AB  - OBJECTIVE: To study the temporal relationships between cytomegalovirus (CMV)
      viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and
      plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV
      retinitis. METHODS: Sequential PMNL and plasma samples were analysed for
      determination of the CMV viral load using non-molecular methods and a
      quantitative polymerase chain reaction (PCR) assay. Screening of the same samples
      for the most common mutations conferring ganciclovir resistance was performed
      using nested PCR and restriction enzyme analysis. RESULTS: At the time of
      progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in
      the CMV DNA load was found in both PMNL and plasma samples. This increase
      paralleled the emergence of a specific mutation (V594) in the same samples and
      recovery of ganciclovir-resistant blood isolates. In this patient, however, the
      only tests that substantially predicted the progression of CMV disease were the
      quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia
      assay. CONCLUSIONS: Quantitative evaluation of the CMV viral load in PMNL using
      sensitive assays such as PCR appears to be a promising approach for monitoring
      antiviral therapy in subjects with AIDS. In addition, common mutations conferring
      ganciclovir resistance can be detected directly in PMNL and plasma samples.

PMID- 9189212
TI  - Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results
      of a randomized controlled trial.
AB  - OBJECTIVES: To determine the efficacy of isoniazid 300 mg daily for 6 months in
      the prevention of tuberculosis in HIV-1-infected adults and to determine whether
      tuberculosis preventive therapy prolongs survival in HIV-1-infected adults.
      DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial in
      Nairobi, Kenya. SUBJECTS: Six hundred and eighty-four HIV-1-infected adults. MAIN
      OUTCOME MEASURES: Development of tuberculosis and death. RESULTS: Three hundred
      and forty-two subjects received isoniazid and 342 received placebo. The median
      CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid
      and placebo groups, respectively. The overall median follow-up from enrolment was
      1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid
      group was 4.29 per 100 person-years (PY) of observation [95% confidence interval
      (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the
      placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92
      (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid
      versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI,
      0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The
      overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95%
      CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate
      ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST
      negative subjects, 1.39 (95% CI, 0.90-2.12). CONCLUSIONS: Overall there was no
      statistically significant protective effect of daily isoniazid for 6 months in
      the prevention of tuberculosis. In the TST-positive subjects, where reactivation
      is likely to be the more important pathogenetic mechanism, there was some
      protection and some reduction in mortality, although this was not statistically
      significant. The small number of individuals in this subgroup made the power to
      detect a statistically significant difference in this subgroup low. Other
      influences that may have diluted the efficacy of isoniazid include a high rate of
      transmission of new infection and rapid progression to disease or insufficient
      duration of isoniazid in subjects with relatively advanced immunosuppression. The
      rate of drug resistance observed in subjects who received isoniazid and
      subsequently developed tuberculosis was low.

PMID- 9189213
TI  - Cost-effectiveness of cytomegalovirus (CMV) disease prevention in patients with
      AIDS: oral ganciclovir and CMV polymerase chain reaction testing.
AB  - OBJECTIVE: To perform a cost-effectiveness analysis of strategies to prevent
      cytomegalovirus (CMV) disease. METHOD: Markov model and published data. PATIENTS:
      Hypothetical HIV-infected patients with CD4 cell counts < or = 50 x 10(6)/l and
      positive CMV serologies. INTERVENTIONS: Oral ganciclovir daily versus plasma CMV
      DNA polymerase chain reaction (PCR) testing every 3 months with oral ganciclovir
      for patients with positive tests. OUTCOME MEASURES: The number of CMV disease
      cases prevented by the interventions, life expectancy, disease-free life
      expectancy, and the cost to extend life by 1 year. RESULTS: Oral ganciclovir
      preventive therapy reduces the lifetime number of CMV disease cases by 50 per
      1000 cohort, extends life expectancy by 5 days and disease-free life expectancy
      by 18 days, and costs US$ 1,762,517 per year of life extended. Periodic PCR
      testing reduces the lifetime number of CMV disease cases by eight per 1000
      cohort, extends life expectancy by 1 day and disease-free life expectancy by 3
      days, and costs US$ 495,158 per year of life extended. The prevention strategies
      could be acceptably cost effective only under a combination of optimistic
      assumptions and reduced costs. CONCLUSIONS: Oral ganciclovir preventive therapy
      and periodic plasma testing for CMV PCR with oral ganciclovir for those with
      positive tests result in small benefits at great cost. They are not cost
      effective prevention strategies for persons with advanced HIV infection and
      positive CMV serologies.

PMID- 9189214
TI  - Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a
      group of HIV-positive patients at high risk of CMV disease.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease is a major cause of morbidity in
      patients with HIV infection. Despite treatment, CMV retinitis causes substantial
      visual loss, especially in patients with CD4 cell counts below 50 x 10(6)/l.
      Although routine ophthalmological screening of these patients has been
      recommended, no controlled trials have evaluated how frequently it should be
      performed. The aim of this study was to assess whether CMV polymerase chain
      reaction (PCR) results could direct ophthalmological screening to patients at
      high risk of CMV retinitis. METHODS: In a prospective study of HIV-positive
      patients with CD4 cell counts below 50 x 10(6)/l, CMV viraemia was detected by
      qualitative PCR of whole blood. Patients who were CMV PCR-viraemic were allocated
      to monthly virological and ophthalmological follow-up; patients who were PCR
      negative received 3-monthly virological and ophthalmological follow-up. CMV viral
      load was determined in all CMV-positive samples using a quantitative competitive
      PCR. RESULTS: Nineteen out of 97 patients developed CMV disease over the first 12
      months of the study. Sixteen (59%) out of 27 patients who were CMV-positive
      developed disease compared with three (4%) out of 70 of patients who were PCR
      negative (P = 0.0001). A positive CMV PCR result was significantly associated
      with the development of disease (P = 0.0001), with a relative hazard of 20.15
      [95% confidence interval (CI), 5.80-69.98]. Median CMV viral load was
      significantly higher in those individuals who went on to develop CMV disease (P =
      0.02). In PCR-positive patients, each 0.25 log10 increase in viral load increased
      the risk of disease (relative hazard, 1.37; 95% CI, 1.15-1.63; P = 0.0004).
      CONCLUSIONS: CMV PCR predicts the development of CMV disease and can be used to
      target ophthalmological resources to those patients at highest risk of retinitis.
      Asymptomatic patients who are PCR-positive represent a high-risk group in whom
      controlled trials of pre-emptive therapy could be conducted.

PMID- 9189215
TI  - Quantification of HIV-1 viral load in lymphoid and blood cells: assessment during
      four-drug combination therapy.
AB  - OBJECTIVE: To assess the antiretroviral effect of a combination of zidovudine,
      didanosine, lamivudine and saquinavir in plasma, peripheral blood mononuclear
      cells (PBMC) and lymph-node mononuclear cells (LNMC) after 8 weeks. METHODS: Ten
      HIV-1 antiretroviral therapy-naive patients were given a combination of oral
      zidovudine (200 mg three times daily), oral didanosine (200 twice a day), oral
      lamivudine (150 mg twice a day) and oral saquinavir (600 mg three times daily).
      HIV-1 plasma RNA was measured by quantitative reverse transcriptase (RT)
      polymerase chain reaction (PCR). Infectious HIV-1 in PBMC and LNMC was measured
      by a coculture technique. HIV-1 RNA in PBMC and LNMC was quantified by RT-PCR.
      Proviral DNA titres in PBMC and LNMC were measured by endpoint dilution PCR. CD4
      T-cells were analysed by flow cytometry. RESULTS: CD4 cell counts rose in all
      patients (mean increase of 125 +/- 71 CD4 cells x 10(6)/l) and the benefit was
      greater for patients with fewer than 350 CD4 cells x 10(6)/l (mean increase of
      159 +/- 74 CD4 cells x 10(6)/l). Plasma HIV-1 RNA decreased exponentially in all
      patients (mean decrease of 3.1 log10 after 8 weeks with a mean half-life of 2.2
      +/- 0.6 days). HIV-1 RNA showed a decrease of 3.07 log10 in PBMC and of 2.1 log10
      in LNMC. The decrease in plasma HIV-1 RNA was consistently associated with the
      decrease in LNMC. These data were supported by a concomitant drop of HIV-1
      infectious titres in PBMC (mean decrease of 1.41 log10) and in LNMC (mean
      decrease of 2.54 log). CONCLUSIONS: These data show a significant antiretroviral
      effect of this four-drug combination in blood and lymphoid tissues. However, a
      greater decrease in HIV-1 RNA was observed in PBMC and in plasma than in lymph
      node cells.

PMID- 9189216
TI  - Decreased incidence of sexually transmitted diseases among trucking company
      workers in Kenya: results of a behavioural risk-reduction programme.
AB  - OBJECTIVE: To establish a cohort of high-risk individuals suitable for HIV
      prevention trials, and to measure changes in sexual behaviour and sexually
      transmitted disease (STD) incidence after a behavioural intervention. DESIGN:
      Prospective cohort study in trucking company depots in Mombasa, Kenya.
      PARTICIPANTS: A total of 556 male HIV-seronegative employees of trucking
      companies. INTERVENTIONS: HIV serological testing, individual counselling, condom
      promotion, STD diagnosis and management. MAIN OUTCOME MEASURES: Sexual risk
      behaviour and symptomatic STD incidence. RESULTS: Using time-trend modelling,
      significant declines in self-reported high-risk sexual behaviour were
      demonstrated during a 1-year follow-up. The percentage of men reporting any
      extramarital sex during the 3-month period prior to a follow-up visit decreased
      from 49% durig the first quarter of follow-up to 36% during the last quarter (P <
      0.001). The decline in reported female sex worker contact was from 12% to 6% (P =
      0.001). Approximately 30% of men reported consistent condom use during
      extramarital sex and this percentage remained unchanged during the study period.
      The incidence of STD declined from 34 per 100 person years (PY) during the first
      quarter to 10 per 100 PY during the last quarter (P = 0.001). Significant
      reductions in gonorrhoea (15 to five cases per 100 PY, P = 0.04), non-gonococcal
      urethritis (10 to two cases per 100 PY, P = 0.05), and genital ulcer disease
      (nine to two cases per 100 PY, P = 0.02) were observed. CONCLUSIONS: Among truck
      company workers who participated in a cohort study in Mombasa, Kenya, there was a
      significant decrease in sex with high-risk partners, but no change in condom use.
      The change in heterosexual risk behaviour was accompanied by a significant
      decrease in incidence of gonorrhoea, non-gonococcal urethritis, and genital ulcer
      disease.

PMID- 9189217
TI  - Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex
      workers in Nairobi, Kenya.
AB  - OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV
      related tuberculosis in a female cohort, and to investigate the relative
      importance of recently transmitted infection and reactivation in the pathogenesis
      of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of
      female sex workers in Nairobi were enrolled in a prospective study. Women were
      followed up regularly and seen on demand when sick. METHODS: Between October 1989
      and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women.
      Standard protocols were used to investigate common presentations. Cases of
      tuberculosis were identified clinically or by culture. All available
      Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS:
      Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV
      infected women; no disease was seen in seronegative sex workers (P = 0.0003). The
      overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV
      infected participants. In purified protein derivative (PPD) skin test-positive
      women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years
      in PPD-negative women. Twenty incident cases (41%) were clinically compatible
      with primary disease. DNA fingerprint analysis of strains from 32 incident cases
      identified two clusters comprising two and nine patients; allowing for index
      cases, 10 patients (28%) may have had recently transmitted disease. Three out of
      10 (30%) patients who were initially PPD skin test-negative became PPD-positive.
      Taken together, 26 incident cases (53%) may have been recently infected. DNA
      fingerprint analysis also identified two (50%) of the four recurrent tuberculosis
      episodes as reinfection. CONCLUSIONS: Substantial recent transmission of
      tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers.
      It may be incorrect to assume in other regions of high tuberculosis transmission
      that active HIV-related tuberculosis usually represents reactivation of latent
      infection.

PMID- 9189218
TI  - Modelling the economic benefits of tuberculosis preventive therapy for people
      with HIV: the example of Zambia.
AB  - OBJECTIVE: To assess the economic benefits and costs of providing isoniazid
      preventive therapy for tuberculosis (TB) in HIV-infected persons in Zambia.
      DESIGN: A spreadsheet model incorporating variables drawn from published studies
      and unpublished data. SUBJECTS: Data drawn from a number of different studies and
      published literature involving a range of subjects. SETTING: Zambia. RESULTS:
      Using data primarily from Zambia we have modelled the costs and benefits of a TB
      preventive therapy programme using daily isoniazid for 6 months. The basecase
      scenario assumes recruitment at a voluntary testing and counselling site where
      HIV seroprevalence is 30%; persons with HIV have a 25% probability of developing
      active TB during their lifetime; two additional cases of TB would be prevented
      per person completing a course of preventive therapy; compliance would be 63%,
      and the efficacy of the isoniazid in preventing active TB of 60%. The costs under
      this scenario would exceed the benefits by a factor of 1.16 [benefit: cost ratio
      (BCR) of 0.86]. However, if preventing one case of TB prevented an additional
      five cases, the benefits would exceed the costs by a significant margin (BCR of
      1.71). Other scenarios indicate that the targeted preventive therapy of persons
      with HIV whose occupation or living situation places them in contact with a large
      number of others (teachers and students, health personnel, military and police,
      miners, prisoners, etc.) would yield significant net benefit. The operational
      challenge for TB preventive therapy is thus to identify and target large numbers
      of such persons.

PMID- 9189219
TI  - Search for infectious HIV in gingival crevicular fluid and saliva of advanced
      AIDS patients with severe periodontitis.

PMID- 9189220
TI  - Low serum cholesterol and risk of death from AIDS.

PMID- 9189221
TI  - Identification of a novel HLA-B*3501-restricted cytotoxic T lymphocyte epitope
      using overlapping peptides.

PMID- 9189222
TI  - Evaluation of rapid on-site clinic HIV test, combined with counselling.

PMID- 9189223
TI  - HIV care in the community: creation of a flowchart to assist in coordinating
      patient care and data management. Stamford HIV/AIDS Care Community Needs Team.

PMID- 9189224
TI  - HIV-1 and HIV-2 AIDS in African patients living in Paris.

PMID- 9189225
TI  - Harm of not permitting personal HIV screening in developing countries.

PMID- 9189227
TI  - Marked hyperlipidaemia on ritonavir therapy.

PMID- 9189226
TI  - A placebo-controlled clinical phase I trial with combined anti-HIV-1 and anti
      interferon-alpha immunization.

PMID- 9189228
TI  - Does HIV-2 protect against HIV-1 infection?

PMID- 9189230
TI  - Dapsone and HIV-1 replication in primary cultures of lymphocytes and monocyte
      derived macrophages.

PMID- 9189229
TI  - Association of maternal drug use during pregnancy with mother-to-child HIV
      transmission. New York City Perinatal HIV Transmission Collaborative Study.

PMID- 9189231
TI  - Chemotherapy for AIDS-related malignancies does not increase HIV viraemia.

PMID- 9189232
TI  - Low HIV prevalence among childbearing women of aboriginal origin.

PMID- 9189233
TI  - Similarity in language in "AIDS" article and "AJE" article.

PMID- 9189234
TI  - The parallels between Asclepian and Hippocratic medicine on the island of Kos.
AB  - At the end of the 20th century, Hippocratic medicine--which developed at the
      cross-roads between the occidental and oriental civilisations--acts as a link, a
      bridge and a symbol for the need to combine both the experience of traditional
      (Eastern) and the trends of modern (Western) medicine. Hippocratic medicine is
      one vital pathway to the proper study of the evolution of the medical art. Not
      only is it the beginning of the art and science of medicine, but modern medicine
      can still learn from the Hellenic medicine of ancient Greece. Hippocratic
      medicine is both an antidote to an overconcentration and overemphasis on medical
      technology and a stimulus to more humane technical achievements. Hippocratic
      bedside examination has not died, but is merely pushed aside temporarily by
      modern technology. The fact that ancient Hellenic medicine was based on the
      coexistence of both Asclepian (traditional) and Hippocratic (rational) medicine
      on the island of Kos reveals and symbolises the necessary coexistence and
      cooperation of both systems, a synthesis of their concepts being essential to
      solve the problems threatening the future of humankind. Hellenic medicine serves
      to highlight that the parallels between Asclepian and Hippocratic medicine are
      closer than medical historians usually realise, and that alternative medicine may
      function in a complementary way to conventional primary medical care.

PMID- 9189235
TI  - Aretaeus on the kidney and urinary tract diseases.
AB  - Hippocratic medicine based on rational thought and clinical observation was the
      first to develop the speciality of nephrology. Five centuries later, Aretaeus of
      Cappadocia incorporated in his writings the achievements of anatomy and
      physiology from the flourishing Alexandrian School of Medicine. His work
      comprises two books on acute and two books on chronic diseases and this
      classification is extended into the field of treatment. Nephrological diseases
      are examined according to the above division and healing methods include, in
      particular, herb therapy.

PMID- 9189236
TI  - Renal diseases in the Hippocratic era.
AB  - Hippocrates and the medical school of Kos were mainly concerned with the common
      elements of various diseases and the accurate description of symptoms and signs,
      as well as their prognostic implications. In contrast, the medical school of
      Knidos (in neighbouring Asia Minor) and its chief member Euryphon were interested
      in the systematic classification of diseases according to the systems involved.
      Galen mentions that Knidian physicians were familiar with four renal diseases,
      probably the same described in the book About Inner Sufferings, whose author is
      not known with certainty; most investigators attribute it to the Knidian school
      (5th century BC), while others consider it to be a Hippocratic work. Both
      theories are logical and possible, since Hippocrates himself was familiar with
      the work of the Knidian school and a rival of Euryphon. The first renal disease
      described in the book is nephrolithiasis with renal colic. Its description is
      considered a classic one and it is well known for its accuracy and clarity. The
      second disease corresponds to renal tuberculosis, while the remaining two are
      somewhat unclear, the third resembles either renal vein thrombosis or bilateral
      papillary necrosis. The fourth disease, described in the greatest detail of all,
      corresponds to a chronic suppurative renal infection or a sexually transmitted
      urethritis, complicated by renal involvement. Some statements concerning
      treatment follow; they consist of diet modification, physical exercise, ingestion
      of herbal extracts and surgery, as a last resort. It is therefore evident that
      Hippocrates is the father of clinical nephrology and that Hippocratic medicine
      lies at the root of the development of clinical nephrology.

PMID- 9189237
TI  - Diseases in the Byzantine world with special emphasis on the nephropathies.
AB  - Using medical manuscripts and texts from the Byzantine period (330-1453), this
      article describes various, to date little discussed, aspects of Byzantine
      nosology, public health and therapeutics. Many diseases in the Byzantine era were
      widespread and had a high morbidity such as respiratory disease, various kinds of
      anaemia, pestilential diseases (e.g. quartan fever, plague, dysentery and
      cholera), parasitic diseases, orthopaedic, rheumatic and psychiatric disorders,
      trachoma and alcoholism. Other very serious and relatively frequent conditions
      included leprosy, mania, gout, cancerous tumours and ulcers. Important elements
      of nephrology and various renal diseases were described and investigated, such as
      acute and chronic renal failure, acute and chronic nephritis, pyelonephritis,
      necrotic renal diseases, crush syndrome, and ulcers of the kidneys, i.e.
      tuberculosis or renal tumours. The microhistology and physiology of the kidneys
      were first studied by Oribasius, who discerned the existence of the capillaries-
      tau rho iota chi omicron epsilon iota delta eta--some centuries before Malpighi.
      He also correctly described the blood circulation, general and pulmonary, as a
      precursor to Harvey. The first hospitals were organised during the Byzantine
      period, and the practice of Byzantine medical science and its social applications
      were regulated by a special medical legislation and deontology. Byzantine
      medicine was fruitfully connected with the Christian faith and developed the
      supreme model of the saints unmercenary--alpha nu alpha rho gamma epsilon rho
      omicron iota--physicians such as Cosmas and Damian (3rd century), Panteleemon
      (3rd-4th centuries) and the women physicians and miracle-worker saints, Zenais
      and Philonilla (1st century), the 'friends of peace', and Hermione (1st-2nd
      centuries).

PMID- 9189238
TI  - Uroscopy in Byzantium.
AB  - Macroscopic examination of the urine has been used since time immemorial for the
      diagnosis and prognosis of nearly every disease. Although the great fathers of
      antiquity, such as Hippocrates and Galen, were involved in the practice, it
      reached its heights during the Middle Ages. This article divides the Middle Ages
      into three periods--early, middle and late--and studies the use of the method and
      the contributions of its particular practitioners in the eastern part of the
      former east Roman Empire (Byzantium). Uroscopy achieved there a more scientific
      status than in Western Europe, at least during the first two periods of the
      Middle Ages, and it also influenced heavily Arabic and Jewish medicine. However,
      Byzantine urosocopy was mainly based on ancient Greek knowledge and was open to
      progressive influences by medical progress in all its neighboring countries.

PMID- 9189239
TI  - The Peri ouron treatise of Stephanus of Athens: Byzantine uroscopy of the 6th-7th
      centuries AD.
AB  - In the 6th-7th centuries AD, treatises on uroscopy were written by Theophilus,
      Magnus and the author of work transmitted through the ms. Parisinus gr. 2260,
      Stephanus of Athens. These works are the first to deal comprehensively with the
      problem of urines, uroscopy and their clinical role, so that a philological and
      content analysis and examination of their reciprocal relationships may clarify an
      important period in the birth and development of Byzantine uroscopy, which
      represents a significant epistemological passage in the medieval history of
      medicine (e.g. the positing of relationships between physical signs and systemic
      diseases).

PMID- 9189240
TI  - Influence of Judaism and Jewish physicians on Greek and Byzantine medicine and
      their contribution to nephrology.
AB  - Both the Old Testament and the Talmud contain a great deal of information on
      medicine, nephrology, health and disease. The basic premise of early Jewish
      medicine is based on the notion that disease is due to structural changes in
      internal organs. This is in contrast to the mythical dogma of humoralism as the
      basis of health and disease espoused by Hippocrates and Galen. The Old Testament
      and the Mosaic Codes provided the basis for modern public health and for the
      hygienic rules practised in our times. The Talmudists laid the foundations for
      the science of pathology as we know it today. These issues are discussed in
      detail and the contributions of three prominent medieval physicians (Asaph
      Judaeus, Isaac Judaeus and Maimonides) are presented.

PMID- 9189241
TI  - Medicinal plants for the treatment of urogenital tract pathologies according to
      Dioscorides' De Materia Medica.
AB  - The De Materia Medica of the Greek Dioscorides reports about 200 plants used for
      the treatment of pathologies of the urogenital tract during the 1st century AD.
      On the basis of explicit and implicit affirmations by Dioscorides, a theoretical
      system concerning the specific properties of these plants has been attempted.
      Comparison of the species reported by Dioscorides and Pliny the Elder for renal
      affections does not support the thesis of a close relationship between De Materia
      Medica and the Naturalis Historia.

PMID- 9189242
TI  - The bursa of Hieronymus Fabrici d'Acquapendente: past and present of an
      anatomical structure.

PMID- 9189243
TI  - The Flemish anatomist Andreas Vesalius (1514-1564) and the kidney.
AB  - Andreas Vesalius was born in Brussels on December 31, 1514 from a long line of
      physicians. He died in Zante in 1564. He was a typical son of the Renaissance. In
      1543, his two most important books were published: De Humani Corporis Fabrica,
      Libri Septum and the Epitome. The former was a book of over 700 pages with
      several illustrations, highly systematically composed and fully indexed. Andreas
      Vesalius was the first modern anatomist who based his anatomical descriptions on
      personal observation. The kidney was a fascinating organ to Vesalius, whose
      function, particularly regarding the production of urine, he did not fully grasp.
      He makes short work of the 'perforated membrane theory' which was the current
      conception of the origin of urine in the kidney. Andreas Vesalius broke with the
      established rigid and fabricated way of teaching anatomy, and introduced the
      modern concept of learning based on personal observations, using illustration
      combined with a critical spirit and sense of experiment.

PMID- 9189244
TI  - Realdo Colombo (1516-1559). A reappraisal.
AB  - A pupil and then the successor of Vesalius to the Chair of Anatomy and Surgery at
      the University of Padua, Matteo Realdo Colombo (1516-1559) was equally consumed
      by the flame of scientific inquiry and recognition. His sole contribution to the
      literature, De Re Anatomica, was published after his death in 1559. In it, he
      correctly describes the position of the right kidney as lower than that of the
      left and provides the best description of the pulmonary circulation before that
      of William Harvey, who in his text duly acknowledged Colombo's contributions. In
      the concluding chapter, he establishes the beginnings of morbid anatomy in
      describing diseased organs. De Re Anatomica was widely used as a textbook of
      anatomy, being translated into English in 1578 and German in 1609. He came to be
      sufficiently well known to become physician to the Vatican. One of his best known
      patients was Michelangelo, with whom he vainly tried to collaborate in
      illustrating De Re Anatomica. A regrettable eventuality, which could have
      reversed the fortunes of Vesalius and Colombo in the annals of the history of
      medicine.

PMID- 9189245
TI  - Marcello Malpighi (1628-1694).
AB  - The current paper is intended as a short but precise illustration of Marcello
      Malpighi's cultural life, a small tribute we deserve to a genius of such sharp
      insight. He made many discoveries in the fields of the macro- and microanatomy of
      the brain, nerves, liver, kidneys, spleen, tegument, lymph nodes, reproductive
      system and other organs, but rather than pursuing these in any detail, we have
      tried to profile Marcello Malpighi's scientific life in the cultural context of
      his time, while also providing some information on the most fascinating phases of
      his research on renal structure and function.

PMID- 9189246
TI  - Guilielmus de Saliceto and his contributions to renal medicine.
AB  - Guilielmus, one of the most outstanding physicians of the 13th century practised
      a bedside teaching method and gave guidelines for diagnosing and treating
      diseases. Written summaries of clinical case histories were his basic didactic
      instruments and his practise was characterized by a high awareness of doctor
      patient relations.

PMID- 9189247
TI  - The famous case of rheumatic hematuria described by Giammatteo Ferrari da Grado,
      professor at the University of Pavia (1432-1472).
AB  - Giammatteo Ferrari da Grado was an influential professor and teacher of medicine
      at the University of Pavia in middle of the 15th century. He authored three
      important texts, among which is the Consilia, a collection of cases he visited
      and/or consulted. Among these, Ferrari describes a case of rheumatic hematuria in
      an eminent patient, Gaston de Foix, prince of Navarre. Following a precise
      description of the symptoms, he makes a complex pathogenic interpretation based
      on the theory of humors current at the time, and goes on to offer his patient a
      generous spectrum of herbal, hygienic and dietetic remedies.

PMID- 9189248
TI  - Cistercian medicinal herbs for renal therapy in the 15th century.
AB  - The rule conceived the monastery as a citadel of divine service so that medicine,
      together with other arts, was the subject of studies and searches which
      contributed to the foundation of monastic medicine. In the 14th and 15th
      centuries, Cistercian monks did not limit themselves to the study of the ancient
      treatises on medicinal herbs, but enlarged their knowledge through clinical
      experience to such an extent that they created the principal therapy of diseases
      for about five centuries.

PMID- 9189249
TI  - History of the science of dialysis.
AB  - Thomas Graham (1805-1869), who is credited with seminal work on the nature of the
      diffusion of gases and of osmotic forces in fluids, can properly be called the
      father of modern dialysis. His apparatus to study the behavior of biological
      fluids through a semipermeable membrane clearly presaged the artificial kidney in
      clinical use today. In 1913, John Abel and coworkers reported the first
      application of the principles of diffusion to remove substances from the blood of
      living animals. Unaware of Abel's work, Georg Haas (1886-1971) performed the
      first human dialysis in the German town of Giessen in 1924. But it was not until
      1945 that Willem Johan Kolff, working under extremely difficult wartime
      conditions in The Netherlands, achieved the first clinically successful
      hemodialysis in a human patient.

PMID- 9189250
TI  - Origins and early reception of clinical dialysis.
AB  - Several medical inventors in Europe and North America brought the artificial
      kidney (hemodialysis) to practical usefulness in the late 1940s, but there were
      very few early successes. It was used at first for only desperate cases of acute
      renal failure. Renal authorities in the 'metabolic' tradition favored newly
      quantified metabolic and dietetic therapies. In part, this resistance to dialysis
      represented reasonable skepticism about results, but also preferences concerning
      what constituted 'science' within medicine.

PMID- 9189251
TI  - A history of natural membranes in dialysis.
AB  - Nature uses various natural membranes to eliminate toxic substances from the
      blood, mainly in renal failure. The membranes used for this purpose are
      predominantly those of the gastrointestinal system and the skin. Humans tried to
      imitate nature, and employed the same membranes for blood purification in
      patients with renal failure. The beginning of the practice can be dated to at
      least 4,000 years ago. However, the initiative for such clearing maneuvers was
      given by the human mind's conception for purifying the cosmos, the polis and the
      soul. This article traces similarities between such metaphysical tactics and
      procedures of the applied sciences. It also describes the historical evolution of
      the use of natural membranes for medical reasons in nephrological patients.

PMID- 9189252
TI  - Hamburger's achievement with early renal transplants.
AB  - In 1947 Hamburger mapped out his course of action to achieve successful renal
      transplantation and then undertook what he had predicted. His steps were as
      follows: in 1952, graft of a kidney from a mother to her son, a failure providing
      more information than any experimental attempt; in 1959, a transplantation from a
      non-identical twin to his irradiated brother, a rare success with this dangerous
      immunosuppression; in 1964, a successful graft from a dead donor, with Dausset's
      introduction of HLA typing to match the donor and the recipient. Hamburger's and
      Crosnier's endeavours were interwoven with those of other physicians and
      surgeons: in Paris, Kuss and Legrain, in Boston, Murray and, especially, Merrill,
      with whom Hamburger shared more than a friendship.

PMID- 9189254
TI  - Depictions of the kidney through the ages.
AB  - Recent publications [American Journal of Nephrology (1985-1995)] have contributed
      much to our understanding of the history of nephrology. Whether the earliest
      medical knowledge of the kidney was kindled in Egypt, by the Hindus in India, in
      ancient China, or by Assyro-Babylonians we cannot determine with certainty. What
      is known is that the invention of the printing press (circa 1450 AD), with the
      subsequent availability of translations of earlier writings plus new text
      editions, contributed in prodigious measure to the development of the critical
      and questioning character of medicine. The availability of different book
      illustration techniques also contributed to the development of medical knowledge.
      We have examined major descriptions of the kidney in 16th-, 17th- and 18th
      century original works, all held by the Becker Medical Library, Washington
      University. The accuracy of illustrations of the observed kidney was highly
      variable, but each description has its place in book and 'kidney' history.

PMID- 9189253
TI  - The symbolism of salt in paintings.
AB  - Many artists have used the symbol of salt in both religious and profane works,
      yet very few studies have explored the symbolism of salt as used in works of art.
      In this study, Panofsky's method has been adopted to evaluate works of art
      through an organic process articulated into three stages: (1) pre-iconographic,
      (2) iconographic and (3) iconological. The method was used for (a) religious
      paintings of the Old and New Testaments and (b) mythological and profane themes.
      Various salt-cellars were also studied. In particular, the paper examines the
      following themes: Isaac blessing Jacob, the return of Esau, Samuel consecrating
      David, the Last Supper, the suppers at Emmaus and at the house of Simon, the
      birth of St. John the Baptist, the Baptism of Constantine, the prodigal son,
      Bacchus-Apollo, the nuptial banquet of Love and Psyche, the death of the Cavalier
      of Celano, the king drinks, the landlord's visit, 'Phitopolis faisant servir des
      mets en or au roi Pithes', certain still life paintings and various salt-cellars
      including those of Cellini and Giulio Romano. The paper discusses the works of
      many artists including Raphael, Leonardo and his school (Boltraffio,
      Giampietrino, d'Oggiono, Solario), Hendricksz, Corenzio, Jean-Baptiste and
      Philippe de Champaigne, Damaskinos, Tintoretto, Titian, Romanino, Rubens,
      Bellini, Bloemaert, Veronese, Sustris, Just of Ghent, Jan Van Hemessen, Poussin,
      Loir, Giotto, Jordaens, Brueghel and Mimmo Paladino with his enchanted mountain.
      From the data examined it emerged that salt is a primary iconological presence in
      various works of art.

PMID- 9189255
TI  - The introduction of renal biopsy into nephrology from 1901 to 1961: a paradigm of
      the forming of nephrology by technology.
AB  - 'Biopsy' (Besnier 1895) became useful towards the end of the 19th century with
      the development of good histology and microbiology. Needle biopsy of the liver,
      although first performed in 1895, did not become current until 50 years later.
      Surgical biopsy of the kidney at incidental operations, particularly the then
      fashionable renal decapsulation, was performed from 1900 to 1930. Percutaneous
      needle renal biopsy was introduced after first, the successful liver biopsy and
      second, demonstration of the value of aspiration needle biopsy in tumours of the
      kidney. In addition, a number of physicians obtained renal tissue by accident and
      without problems during intended biopsies of the liver. Nils Alwall of Sweden
      performed the first systematic aspiration needle biopsies of the kidney in 1944,
      but did not publish his results because of an early death which led him to
      abandon the technique. However, when Iversen and Brun in Copenhagen described
      their results in 1951, a number of physicians around the world immediately began
      to attempt renal biopsy, using cutting as well as aspiration techniques. Success
      was inconsistent and operator dependent: the refinements of technique and needles
      introduced by the group in Chicago led by Robert Kark, plus their advocacy of the
      technique and their training of many physicians in its performance rapidly led to
      widespread acceptance. New techniques of immunofluorescence and electron
      microscopy arrived at the same time so that the technique could be fully
      exploited. The performance and interpretation of renal biopsies became, along
      with classical whole-organ and nephron physiology and the introduction of
      dialysis and transplantation, powerful agents determining the emergence of
      Nephrology as a specialty around 1960.

PMID- 9189256
TI  - Unravelling dropsy: from Marcello Malpighi's discovery of the capillaries (1661)
      to Stephen Hales' production of oedema in an experimental model (1733).
AB  - A modern understanding of oedema formation traditionally begins with Starling's
      description in 1898 of hydrostatic and oncotic forces acting on the capillary
      membrane. Clearly, hypotheses of oedema formation predating the knowledge of the
      existence of capillaries must have been incomplete. Marcello Malpighi first
      described capillaries in 1661, but although he displayed a good grasp of the
      principles of the Harveian circulation and believed that oedema fluid (the
      clinical entity dropsy) was derived from the blood rather than the tissues, we
      have found no evidence that he realised the central role played by his discovery.
      However, only 60 years later, Stephen Hales' Haemastaticks reveals the creation
      of an experimental model for dropsy which led him towards an understanding of
      oedema formation not far behind Starling.

PMID- 9189257
TI  - Renal imaging techniques.
AB  - The ancient approach to obtain an image of the kidneys (and other internal
      organs) was 'section-inspection-imaging' by drawing, painting, sculpturing, and
      modelling. The present study follows chronologically the development and use of
      sectioning techniques from ancient (often forbidden) methods to modern
      microdissection and maceration of silicone-rubber-injected tubules. Inspection
      evolved from the use of the naked eye to magnifying lenses, microscopes and
      finally electron microscopy. Pertinent examples such as the description of the
      kidneys as the site of urine formation, the visualization of loop structures in
      the renal medulla and the imaging of tight junction strands are discussed.
      Inspection or visualization of renal structure and function has been
      revolutionized by modern noninvasive techniques, such as X-ray imaging, imaging
      by radioisotopes, ultrasound, computer tomography and nuclear magnetic resonance.
      Pertinent examples are given demonstrating the potency of the various techniques.
      The contribution of computerized data evaluation is discussed. The development of
      micropuncture and microperfusion techniques has opened the field for direct
      imaging not only of renal (sub)structural details but also of functional
      parameters such as transtubular reabsorption rates, single glomerular capillary
      filtration and conductance of the paracellular pathway. We focus particularly on
      techniques specifically designed to visualize renal hemodynamic and transport
      parameters.

PMID- 9189258
TI  - History of vitamin D treatment of renal osteodystrophy.
AB  - Vitamin D treatment was tried when renal osteodystrophy was first recognized in
      the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses
      of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum
      calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25
      dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was
      applied to the treatment of renal osteodystrophy. In a preclinical study,
      especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the
      most responsive condition. These active vitamin D preparations are now widely
      used in patients with chronic renal failure under hemodialysis. Other active
      vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22
      oxacalcitriol, are also under investigation.

PMID- 9189259
TI  - Richard Bright in Hungary: a reevaluation.
AB  - Richard Bright, the highly respected physician and nephrologist at Guy's
      Hospital, had a strong liking for travel. In 1815 he traveled in Hungary and made
      very important observations about the country. His 762-page book, entitled
      Travels from Vienna through Lower Hungary has detailed, sometimes appreciative,
      sometimes very critical remarks and comments on Hungarian history, art,
      archeology, religion, the situation of nationalities, education, social
      conditions, law, farming, and mining. The Hungarians cherished the memory of
      Bright's travel in their country as reflected in several papers and on two
      commemorative tablets recognizing him as a true and sincere friend of Hungary.

PMID- 9189260
TI  - History of the crush syndrome: from the earthquakes of Messina, Sicily 1909 to
      Spitak, Armenia 1988.
AB  - Man-made or massive natural disasters may be followed by 'epidemics' of the
      muscle crush syndrome. The first descriptions of the crush syndrome were in the
      German-language literature following the earthquake of Messina in 1909 and World
      War II. On the threshold of World War II, the English-language literature was
      still unaware of the crush syndrome. During the London Blitz in 1940, Bywaters
      clearly delineated the pathogenesis of the crush syndrome and established
      guidelines for the management of casualties. The experience from the war in
      southern Lebanon in 1982 showed that early volume repletion can prevent acute
      renal failure in casualties with the crush syndrome. Following the major
      earthquake at Spitak in 1988, massive international relief effort helped to
      rescue and salvage many casualties. International preparedness contingency plans
      will increase the survival of future casualties suffering from crush injury.

PMID- 9189261
TI  - Impairment of visual object-discrimination learning after perirhinal cortex
      ablation.
AB  - Eight cynomolgus monkeys learned preoperatively 20 concurrent visual
      discriminations between pairs of colored shapes presented on a touch screen with
      24-hr intertrial intervals. Three then received bilateral perirhinal cortex
      ablation, and 5 remained controls. The ablated monkeys were severely impaired in
      reacquiring the preoperatively acquired set, whereas postoperative learning of 20
      new discriminations was not significantly affected. The task was then made more
      difficult. First, the number of foils from which the stimulus had to be selected
      was increased to 2, 4, 7, and then 14. Second, larger sets of 40, 80, and 160
      problems were presented. Both manipulations revealed some significant but
      relatively mild impairments in the monkeys with ablations. It is suggested that
      perirhinal cortex ablation impairs the monkey's capacity to identify individual
      objects, which leads to deficits in both visual-object recognition memory and
      discrimination learning.

PMID- 9189262
TI  - Lesions of the perirhinal cortex interfere with conditioned excitation but not
      with conditioned inhibition of fear.
AB  - Posttraining lesions of the perirhinal cortex (Prh) have been shown to interfere
      with the expression of fear. This study assessed whether Prh lesions would also
      disrupt the inhibition of fear as measured with conditioned inhibition of fear
      potentiated startle. Following light + shock, noise-->light-no shock conditioned
      inhibition training, rats were given Prh lesions. The lesions interfered with the
      expression of fear-potentiated startle to the light. To assess whether
      conditioned inhibition was affected, the rats were given light + retraining
      without additional noise-->light-training. The noise-conditioned inhibitor
      retained its ability to inhibit fear-potentiated startle to the retrained light.
      These results suggest that the areas of the Prh that are essential for the
      initial expression of conditioned fear are not important for the expression of
      conditioned inhibition of fear.

PMID- 9189263
TI  - Dissociable effects of selective lesions to hippocampal subsystems on exploratory
      behavior, contextual learning, and spatial learning.
AB  - Rats received excitotoxic lesions of different subsystems within the hippocampal
      system--either the hippocampus proper (cornu ammonis and dentate gyrus;
      hippocampal lesions) or the entorhinal cortex-subicular region (entorhinal
      lesions). Subsequently, their activity in an operant chamber was monitored both
      before and after footshock had been delivered (Experiment 1). Rats with
      hippocampal lesions showed enhanced activity before the delivery of footshock and
      reduced freezing after the delivery of shock. Rats with entorhinal lesions showed
      control levels of activity before the delivery of footshock and control levels of
      freezing after the delivery of footshock. Both types of lesion impaired spatial
      learning in a water maze (Experiment 2). These results suggest that the deficits
      arising from damage to the hippocampal system in contextual and spatial learning
      have different origins.

PMID- 9189264
TI  - Autonomic and behavioral correlates of appetitive conditioning in rats.
AB  - The cardiac responses accompanying conditioned stimulus- (CS)-generated
      (orienting) and unconditioned stimulus- (US)-generated appetitively motivated
      behaviors (P. C. Holland, 1977) were investigated. On the basis of contemporary
      psychophysiological research, CS-generated responses were predicted to produce
      bradycardia, and US-generated responses to produce tachycardia. Pairing a 10-s
      visual CS with food delivery produced conditioned behavioral orienting (rearing)
      during the initial portion of the CS, followed by magazine approach (US
      generated) responses as the CS progressed. CS onset produced a decrease in heart
      rate, mediated by an increase in parasympathetic stimulation of the heart, which
      persisted throughout the 10-s CS; no support for a biphasic cardiac response was
      observed. These data are discussed with respect to other conditioned autonomic
      responses and their relevance to foraging and food ingestion.

PMID- 9189265
TI  - A selective role for corticosterone in contextual-fear conditioning.
AB  - The contribution of corticosterone to contextual- and auditory-cue fear
      conditioning was examined. Adrenalectomized rats showed reduced contextual-fear
      conditioning when tested 24 hr after conditioning; however, neither immediate
      contextual- nor auditory-cue fear conditioning was impaired. Contextual-fear
      conditioning in adrenalectomized rats with corticosterone replacement during the
      4-day interval separating surgery and conditioning matched the level of controls.
      Moreover, rats exposed to the context prior to adrenalectomy showed normal long
      term contextual-fear conditioning. Corticosterone replacement administered after
      the conditioning episode also negated the effects of adrenalectomy. Thus,
      corticosterone's role in fear conditioning is selective: It appears to contribute
      to the neural processes that support the consolidation of a long-term memory
      representation of the context.

PMID- 9189266
TI  - DHEA-S selectively impairs contextual-fear conditioning: support for the
      antiglucocorticoid hypothesis.
AB  - The authors had reported that glucocorticoids play a selective role in fear
      conditioning. The adrenal steroid dehydroepiandrosterone (DHEA) has been reported
      to act as a functional antiglucocorticoid. If DHEA has antiglucocorticoid
      properties, then its effects on fear conditioning might resemble those produced
      by adrenalectomy. The authors now report that chronic exposure to high levels of
      dehydroepiandrosterone sulfate (DHEA-S; converted in vivo to DHEA) produced the
      same pattern of results as adrenalectomy. Specifically, treatment with DHEA-S
      impaired contextual fear conditioning 24 hr after conditioning but not
      immediately after conditioning, and like adrenalectomy, DHEA-S had no effect on
      auditory-cue fear conditioning. Preexposure to the context before drug treatment
      eliminated the amnestic effects of DHEA-S, suggesting that, like adrenalectomy,
      DHEA-S exerted its effect by interfering with the construction of a contextual
      memory representation. Thus, DHEA appears to act as a functional
      antiglucocorticoid in the processes that mediate learning and memory.

PMID- 9189267
TI  - Acute corticosterone replacement reinstates performance on spatial and nonspatial
      memory tasks 3 months after adrenalectomy despite degeneration in the dentate
      gyrus.
AB  - Long-term adrenalectomy (ADX) causes loss of spatial memory and of dentate gyrus
      cells. These effects are prevented by chronic replacement of corticosterone
      (CORT). The effects of acute replacement 3 months after ADX in rats classified as
      ADX or incomplete ADX (INC) on the basis of saline intake, weight, and plasma
      CORT levels were investigated. ADX rats swam longer and farther to find a
      platform in a spatial water-maze task (Exp. 1) and were impaired on a nonspatial
      object-recognition task (Exp. 2) compared with INC and SHAM rats. In both
      experiments, ADX decreased the size of the dentate gyrus, and replacement with
      CORT either 5 or 10 days prior to and during testing restored the performance of
      ADX rats without affecting the size of the dentate. CORT did not affect INC and
      SHAM rats. Thus, the adverse effects of ADX on memory may not be due to damage in
      the dentate, and the effects of CORT replacement may operate outside the
      hippocampus.

PMID- 9189268
TI  - Analyses of response patterns clarify lead effects in olfactory reversal and
      extradimensional shift tasks: assessment of inhibitory control, associative
      ability, and memory.
AB  - Rats exposed to lead (Pb) chronically from conception were tested on (a) an
      olfactory serial reversal task and (b) an extradimensional shift (EDS) task. Pb
      exposure did not impair learning of the original olfactory discrimination but did
      impair learning of the 5 reversals and the EDS task. In the reversals, Pb
      exposure tended to shorten the initial period of persistent responding to the
      previously correct cue, but significantly prolonged the postperseverative
      learning phase (both the "chance" and "greater-than-chance" components). These
      effects are similar to those produced by lesions of the amygdala, a structure
      implicated in the process by which stimuli acquire incentive value. This
      similarity, coupled with the pattern of findings, suggests that Pb-induced
      impairment of reversal learning is due to a deficiency in learning the new
      contingencies of the task (an associative deficit), not inflexibility or
      deficient inhibitory control. These findings also illustrate the importance of
      analyzing the types of errors committed, rather than focusing solely on learning
      rate.

PMID- 9189269
TI  - Double dissociation of hippocampal and dorsal-striatal memory systems by
      posttraining intracerebral injections of 2-amino-5-phosphonopentanoic acid.
AB  - Rats received an 8-trial training session on a spatial or cued task in a water
      maze, followed by a posttraining intracerebral injection of AP5 or saline. On a
      retention test 24 hr later, latency to mount the escape platform was used as a
      measure of memory. Intrahippocampal (10 micrograms), but not intra-dorsal
      striatal (2, 5, or 10 micrograms), injection of AP5 impaired memory in the
      spatial task. In contrast, intra-dorsal striatal (2 micrograms), but not
      intrahippocampal (2, 5, or 10 micrograms) injection of AP5 impaired memory in the
      cued task. Intracerebral injections of AP5 delayed 2 hr posttraining were
      ineffective. The findings indicate a double dissociation of the roles of the
      hippocampus and dorsal striatum in memory, a role for N-methyl-D-aspartate
      receptor function in posttraining memory processes, and a glutamatergic
      modulation of both hippocampal and dorsal striatal memory processes, suggesting
      that different forms of memory may share a similar neurochemical basis.

PMID- 9189270
TI  - Analysis of galanin and the galanin antagonist M40 on delayed non-matching-to
      position performance in rats lesioned with the cholinergic immunotoxin 192 IgG
      saporin.
AB  - Galanin is a 29-amino-acid neuropeptide that is overexpressed in Alzheimer's
      disease (AD) and impairs performance on rodent learning and memory tasks. M40, a
      peptidergic galanin receptor ligand, blocks galanin-induced impairments on
      delayed non-matching-to-position (DNMTP). The present experiments used the 192IgG
      saporin lesion model of AD to evaluate the actions of galanin and M40 on DNMTP
      when cholinergic transmission was reduced. Hippocampal choline acetyltransferase
      levels were correlated with DNMTP choice accuracy in lesioned rats.
      Intracerebroventricular (icv) galanin reduced choice accuracy in both the
      lesioned and sham groups. M40 alone, either icv or intrahippocampal, did not
      affect choice accuracy in either group. These results suggest that excess galanin
      can produce further deficits in DNMTP performance in a lesion model of AD, but
      blocking endogenous galanin is not sufficient alone to improve performance in
      lesioned rats.

PMID- 9189271
TI  - Cold shock before associative conditioning blocks memory retrieval, but cold
      shock after conditioning blocks memory retention in Caenorhabditis elegans.
AB  - The effects of cooling on associative learning and memory processes in
      Caenorhabditis elegans were investigated by giving the worms cold shock at
      various times before or after conditioning. A pretraining cold shock in the 30
      min immediately before conditioning and a posttraining cold shock in the 30 min
      immediately after conditioning both disrupted learning and memory processes
      tested a short time after conditioning. However, if tested 3 hr after
      conditioning, worms given a pretraining cold shock demonstrated learned
      preferences, whereas worms given a posttraining cold shock still had memory
      deficits. These results suggest that the effects of cold shock on associative
      learning and memory can be dissociated into effects on memory retrieval and
      memory retention.

PMID- 9189272
TI  - Disruption of the dopamine beta-hydroxylase gene in mice suggests roles for
      norepinephrine in motor function, learning, and memory.
AB  - Mice unable to synthesize norepinephrine (NE) were created by targeted disruption
      of the dopamine beta-hydroxylase (DBH) gene. DBH-deficient (DBH -/-) mice display
      normal home cage activity; however, they swim more slowly than their littermates,
      and some drown. The mutant mice also perform less well on a rapidly rotating rod,
      and approximately 20% do not learn to walk when the rod begins to turn.
      Restoration of NE with dihydroxyphenylserine eliminated these motor deficits. DBH
      -/- mice exhibit normal learning and retention of a passive avoidance paradigm;
      however, they do not master an active-avoidance paradigm as readily as controls
      and exhibit more rapid extinction of the active-avoidance task. DBH -/- mice
      learn to find the hidden platform in the Morris water maze in spite of their
      slower swim speed and show normal preference for the correct quadrant in the
      transfer test immediately after training. However, this preference declines
      relative to controls during the next 2 days.

PMID- 9189273
TI  - Free-field binaural unmasking in budgerigars (Melopsittacus undulatus).
AB  - The detection of signals in noise is important for understanding both the
      mechanisms of hearing and how the auditory system functions under more natural
      conditions. In humans, the auditory system gains some improvement if the signal
      and noise are separated in space (binaural masking release). Birds with small
      heads are at a disadvantage in separating noise and signal sources relative to
      large mammals, because interaural time differences are much smaller. Two binaural
      phenomena in budgerigars related to the detection of tones in noise were
      examined. Budgerigars show 8 dB of free-field binaural masking release when
      signal and noise are presented to their right side and correlated noise is
      presented to their left side. Budgerigars also show a spatial masking release of
      9 dB when a signal and noise are separated in azimuth by 90 degrees. These
      results are similar to those found in humans and other mammals with much larger
      heads.

PMID- 9189274
TI  - Species differences in V1a receptor gene expression in monogamous and
      nonmonogamous voles: behavioral consequences.
AB  - Arginine vasopressin modulates a number of species-typical social behaviors,
      including social memory in rats, scent marking and aggressive behavior in
      hamsters, and partner preference formation and paternal behavior in monogamous
      rodents. The distribution of V1a receptor binding sites in the brain varies
      greatly among species. Using in situ hybridization in 2 species of voles with
      strikingly different patterns of V1a binding sites and social behaviors, the
      authors demonstrate that differences in V1a receptor binding sites are due to
      species differences in regional V1a receptor gene expression. It is then
      demonstrated that the differences in receptor gene expression are associated with
      species differences in behavioral response to centrally administered vasopressin.
      Together, these data suggest that the phylogenetic plasticity of central
      neurohypophyseal peptide receptor expression may contribute to the evolution of
      species-typical social behaviors.

PMID- 9189275
TI  - Dopamine and sodium appetite: antagonists suppress sham drinking of NaCl
      solutions in the rat.
AB  - Sodium (Na) ingestion in rats depleted of Na is a strong, motivated behavior that
      is enhanced further when depleted rats are sham drinking. Dopamine plays a
      critical role in motivation, including reward associated with consumption of
      palatable tastes. The present studies assessed the role of dopamine in real and
      sham drinking of NaCl solutions after Na depletion with the diuretic furosemide
      (10 mg/kg). Dopamine (D2) receptor antagonists were evaluated (Haloperidol [0.1
      mg/kg] and raclopride [0.2 mg/kg]), for their effects on sham and real drinking
      of 0.3 M NaCl. Sham drinking was markedly reduced by both antagonists whereas
      real drinking was unaffected. These effects did not appear to be due to malaise
      or suppression of motor behavior because drug-treated animals were able to
      increase ingestion substantially when offered less concentrated NaCl (0.1 M).
      These results suggest that the positive motivating properties of NaCl stimulation
      in depleted, sham-drinking rats are mediated by central D2 receptors.

PMID- 9189276
TI  - Intragastric carbohydrate exerts both intake-stimulating and intake-suppressing
      effects.
AB  - Ingestion-contingent infusions of 6% carbohydrate did not affect saccharin intake
      during the first ingestive bout, but later they greatly stimulated ingestion,
      slowed the rate of decline of ingestion during bouts, and increased the average
      bout size. This suggests that the intake-stimulating effect of carbohydrate
      infusions is partly attributable to conditioned desatiation. Satiation can also
      be conditioned because more concentrated infusions (24% carbohydrate) did not
      increase daily intake or average bout size, even though both concentrations
      stimulated ingestion during the first 0.5-6.0 min of a test session, as well as
      during extinction tests when only water was infused. Increased intake may be
      partly mediated by a hedonic mechanism because naloxone, an opioid antagonist,
      decreased intake in rats infused with carbohydrate to a greater degree than it
      decreased intake in rats infused with water.

PMID- 9189277
TI  - Rats with area postrema lesions have lengthy eating and drinking bouts when fed
      ad libitum: implications for feedback inhibition of ingestive behavior.
AB  - Ad libitum ingestive behavior of rats with area postrema lesions (APX) was
      monitored electronically every 6 s for 23 hr. Whereas control rats ate on average
      32.2 g of food each day in 16.3 distinct bouts, rats with APX ate comparable
      amounts of food (28.6 g) in much fewer daily bouts (5.8) that were very large.
      Controls drank 38.4 ml of water daily in 17.8 bouts, whereas rats with APX
      consumed more than twice as much water (101.5 ml) in a similar number of bouts
      (18.5). Controls drank 5.3 ml of 0.5 M NaCl daily in 7.0 bouts, whereas rats with
      APX consumed 9 times as much saline (45.5 ml) in more bouts (18.2) that were
      relatively large. These and other results suggest that the area postrema plays an
      important role in detecting inhibitory signals generated by food or fluid intake
      and that feeding and drinking bouts may increase in size after APX, because the
      feedback inhibition provided by those signals is diminished.

PMID- 9189278
TI  - Gustatory functions, sodium appetite, and conditioned taste aversion survive
      excitotoxic lesions of the thalamic taste area.
AB  - Rats with bilateral, electrophysiologically guided, ibotenic acid lesions of the
      gustatory thalamus (THLX) were tested for their ability to perform a variety of
      taste-guided behaviors. First, in daily 30-min sessions, the rats were given
      repeated 10-s access periods to a range of concentrations of sucrose, NaCl, or
      QHCl, plus water. Both the control and the THLX rats exhibited similar
      concentration-response functions, regardless of hydrational state. Next, on 3
      trials, the rats were given 15 min access to 0.3 M l-alanine and then injected
      with LiCl (0.15 M, 1.33 ml/100 g body weight ip). All rats learned a taste
      aversion following 1 pairing with LiCl. Finally, on 3 separate occasions, the
      rats were injected with furosemide, and Na(+)-appetite was evaluated 24 hr later.
      All rats expressed an equivalent sodium appetite after the first furosemide
      injection, but only the control rats increased intake of 0.51 M NaCl with
      repeated sodium depletions. These observations reinforce prior data implying that
      an intact gustatory thalamus is not necessary for the expression of some taste
      guided behaviors.

PMID- 9189279
TI  - Lack of effects of lesions of the dorsal noradrenergic bundle on behavioral
      vigilance.
AB  - The effects of 6-hydroxydopamine (6-OHDA)-induced lesions of the dorsal
      noradrenergic bundle (DNB) were assessed in animals trained in a task designed to
      measure sustained attention, or vigilance. Infusions of 6-OHDA reduced frontal
      cortical noradrenaline contents but did not significantly affect striatal and
      hypothalamic noradrenaline contents. The performance of lesioned animals did not
      differ significantly from sham-lesioned controls. The performance of both the
      lesioned and sham-lesioned animals was impaired by the presentation of a visual
      distractor and by a decrease in the probability for a signal. The results from
      this study largely coincide with the results from previous studies on the effects
      of noradrenergic lesions on various aspects of attention. In contrast to the
      attentional functions assessed in this experiment, the ability to detect and
      select stimuli that are associated with activation of sympathetic functions is
      hypothesized to be sensitive to the effects of DNB lesions.

PMID- 9189280
TI  - Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid
      lesions.
AB  - Fear reactions of rats given bilateral lesions to the septum, hippocampus, or
      amygdala were compared with those of rats given sham lesions, in 2 animal models
      of anxiety: the shock-probe burying test and the elevated plus-maze test. Septal
      lesions produced anxiolytic effects in both tests (i.e., an increase in open-arm
      activity and a decrease in burying), whereas hippocampal and amygdaloid lesions
      produced neither of these effects. On the other hand, hippocampal and amygdaloid
      lesions impaired rats' passive avoidance of the electrified shock-probe, whereas
      septal lesions did not. These dissociations suggest that limbic structures such
      as the septum, amygdala, and hippocampus exert parallel but distinct control over
      different fear reactions.

PMID- 9189281
TI  - The Internet.

PMID- 9189282
TI  - Second chance.

PMID- 9189283
TI  - Recent progress in drug advertising.

PMID- 9189284
TI  - Are low-risk maternity clinics financially viable?

PMID- 9189285
TI  - Thoughts on the importance of being different.

PMID- 9189286
TI  - Drugs and herbal preparations: how safe are they?

PMID- 9189287
TI  - Accessing primary care services.

PMID- 9189288
TI  - Practice intensity: urban vs rural.

PMID- 9189289
TI  - Family medicine in Hong Kong. Present and future.

PMID- 9189290
TI  - Therapeutic abortions due to severe morning sickness. Unacceptable combination.

PMID- 9189291
TI  - Ophthaproblem. Central retinal vein occlusion.

PMID- 9189292
TI  - Dermacase. Gardner's syndrome.

PMID- 9189293
TI  - Removal of fish-hooks.

PMID- 9189294
TI  - Can we diagnose deep-vein thrombosis clinically?

PMID- 9189295
TI  - What is the best medical treatment for benign prostate hyperplasia?

PMID- 9189296
TI  - Maternity care and maternal serum screening. Do male and female family physicians
      care for women differently?
AB  - OBJECTIVE: To examine whether male and female family physicians practise
      maternity care differently, particularly regarding the maternal serum screening
      (MSS) program. DESIGN: Mailed survey fielded between October 1994 and March 1995.
      SETTING: Ontario family practices. PARTICIPANTS: Random sample of 2000 members of
      the College of Family Physicians of Canada who care for pregnant women. More than
      90% of eligible physicians responded. MAIN OUTCOME MEASURES: Attitudes toward,
      knowledge about, and behaviour toward MSS. RESULTS: Women physicians were more
      likely than men to practise part time, in groups, and in larger communities. Men
      physicians were more likely to perform deliveries; women were more likely to do
      shared care. Despite a shorter work week, on average, female physicians cared for
      more pregnant women than male physicians did. Among those providing intrapartum
      care, women performed more deliveries, on average, than men. Women physicians
      were more likely than men to offer MSS to all pregnant patients. Although average
      time spent discussing MSS before the test was similar, women physicians had
      better knowledge of when best to do the test and its true-positive rate. All
      differences reported were statistically significant (P < or = 0.001).
      CONCLUSIONS: Among family physicians caring for pregnant women, women physicians
      cared for more pregnant women than men did. Both spent similar time discussing
      MSS with their patients before offering screening, but more women physicians
      offered MSS to all their patients and were more knowledgeable about MSS than men
      physicians.

PMID- 9189297
TI  - Do women physicians do more STD prevention than men? Quebec study of recently
      trained family physicians.
AB  - OBJECTIVES: To examine differences attributable to sex of family physicians in
      their practices and in their perceptions of sexual history taking and safer sex
      counseling, and to ascertain whether sex of physicians influences counseling
      about condoms. DESIGN: Cross-sectional survey. SETTING: Quebec family practices.
      PARTICIPANTS: Recently graduated (1991) Quebec family physicians: 54 men and 92
      women. MAIN OUTCOME MEASURES: Frequency and content of sexual history, frequency
      of safer sex counseling, perceived level of comfort in taking a sexual history,
      perceived adequacy of medical training to take sexual histories, perceived
      difficulty with sexual history taking according to patients' characteristics, and
      perceived effectiveness of safer sex counseling. RESULTS: Response rate was 80%
      of 183 physicians contacted. There were few differences attributable to sex of
      physician in family physicians' practices and perceptions regarding sexual
      history taking. Men's perceptions regarding the difficulty of sexual history
      taking did not vary according to patient's sex, but most women reported more
      difficulty with male patients. Male physicians reported more difficulty with
      teenagers; female physicians experienced more difficulty questioning adults. More
      than 85% of male and female physicians reported recommending condom use to a
      patient in their practice at least weekly. Women physicians seemed to do more
      condom-related counseling than their male colleagues, even after controlling for
      other variables. Salaried practice in a local community health centre did not
      influence condom-related counseling. CONCLUSIONS: Women family physicians are
      more inclined than men to counsel patients about condom use. Increasing numbers
      of women in family practice could have a beneficial effect on prevention of STDs
      and undesired pregnancies.

PMID- 9189299
TI  - Internet resources for family physicians.
AB  - PROBLEM BEING ADDRESSED: The internet has experienced tremendous growth over the
      past few years and has many resources in the field of family medicine. However,
      many family physicians remain unaware of how the Internet can be used to enhance
      their practice and of how to gain access to this powerful tool. OBJECTIVE OF
      PROGRAM: To characterize components of the Internet, to explore how family
      physicians can use the Internet to enhance practice, and to increase awareness of
      how to gain access to Internet sites relevant to family medicine. MAIN COMPONENTS
      OF THE PROGRAM: An on-line search through the World Wide Web was conducted using
      multiple search engines including Lycos, WebCrawler, OpenText, and Yahoo as well
      as a conventional MEDLINE search of Internet publications for the past 5 years. A
      website containing an evolving selection of resources can be found at http:@dfcm
      18.med.utoronto.ca/anthes/hpgdfcm1.htm. CONCLUSION: The Internet has useful
      applications and resources for family physicians including rapid communication
      between physicians, access to medical literature, continuing medical education
      programs, and lists of patient support and discussion groups.

PMID- 9189298
TI  - Impact of psychotherapy. Does it affect frequency of visits to family physicians?
AB  - OBJECTIVE: To investigate whether a course of psychotherapy with a psychologist
      affected the frequency of patients' visits to their family doctors. DESIGN:
      Retrospective analysis of patients' medical records to determine the frequency of
      visits to their family doctors in the 6 months before psychotherapy, during
      therapy, and in the 6 months after therapy. SETTING: A teaching family medical
      centre in London, Ont. PARTICIPANTS: Thirty-three patients who had completed a
      course of psychotherapy between 1984 and 1991. INTERVENTIONS: Psychotherapy was
      provided by two psychologists employed at the medical centre. Patients did not
      pay a direct fee. The median length of psychotherapy was 12.5 1-hour sessions,
      and the therapeutic approach was eclectic and humanistic. MAIN OUTCOME MEASURES:
      Frequency of visits to family physicians before, during, and after psychotherapy.
      RESULTS: Frequency of visits to family doctors decreased both during and after
      psychotherapy. The decrease was especially apparent from before therapy to after
      therapy (49%, P < .001). Psychotherapy given by psychologists in a Canadian
      family medical centre appears to follow the pattern of the "offset effect," a
      reduction in medical use following psychotherapy, which has been demonstrated in
      other medical settings. CONCLUSIONS: Psychotherapy can be an effective and
      efficient part of total medical care for patients with complex psychological
      problems.

PMID- 9189300
TI  - Dilemma of rural obstetrics. One community's solution.
AB  - PROBLEM BEING ADDRESSED: Increasing workload and concerns about physician
      exhaustion necessitated reorganizing the delivery of obstetric services on
      Manitoulin Island in Ontario. OBJECTIVE OF PROGRAM: To organize obstetrics in a
      remote rural community to provide safe, accessible care, improve working
      conditions for local physicians, and involve the local hospital and health care
      workers in the solution. MAIN COMPONENTS OF PROGRAM: A prenatal clinic for all
      obstetric care on the island was established. It was based at the local hospital
      and organized by a nurse-midwife. Local physicians rotated through the clinic and
      provided obstetric coverage on their on-call days. CONCLUSIONS: The clinic has
      helped improve working conditions for local physicians and maintain high-quality
      obstetric care in this remote area. Local women's initial resistance to the
      clinic seems to be disappearing with time. Ongoing chart audits reveal
      intervention rates similar to those found in other Canadian studies of rural
      obstetric care.

PMID- 9189301
TI  - Case report: acromegaly.

PMID- 9189302
TI  - Morphological adaptations of neuromuscular junctions depend on fiber type.
AB  - The neuromuscular junction (NMJ) forms the communicative link between motoneurons
      and muscle fibers. The properties of motoneurons and muscle fibers are matched in
      different types of motor units, which are recruited selectively to accomplish
      various motor behaviors. Motor units and muscle fibers can be classified based
      upon structural and functional properties, reflecting the essential match between
      motoneuron and muscle fiber. Using a three-color immunofluorescence technique
      combined with confocal microscopy, we examined the three-dimensional structure of
      pre- and postsynaptic elements of NMJs on different fiber types in the rat
      diaphragm muscle. On type I and IIa fibers, comprising slow-twitch and fast
      twitch fatigue-resistant motor units, the structure of NMJs is far less complex
      than on type IIx6 and IIb fibers comprising fast-twitch fatigue-intermediate and
      fast-twitch fatigable motor units. We also found a greater extent of overlap
      between pre- and postsynaptic elements of NMJs on type I and IIa fibers. This
      review focuses on these normal phenotypic differences in NMJ properties and on
      the adaptations that occur under various conditions of altered use.

PMID- 9189303
TI  - Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen
      deficit.
AB  - The purpose of this study was to test the hypothesis that ingestion of creatine
      monohydrate increases anaerobic exercise capacity, as reflected by the maximal
      accumulated oxygen deficit (MAOD). Subjects were assigned, double-blind, to
      placebo (PL, n = 12) or creatine (CR, n = 14) groups and ingested 5-g doses 4
      times daily of artificial sweetener or artificially sweetened creatine
      monohydrate, respectively, for 5 days. On a separate day subjects exercised to
      exhaustion at 125% VO2max. After two familiarization trials, MAOD was again
      determined before treatment, after 5 days of PL or CR treatment, and 7 days
      later. MAOD increased after CR treatment from 4.04 +/- 0.31 to 4.41 +/- 0.34 L (p
      < .001) and remained elevated for another 7 days (4.31 +/- 0.33, p < .001). Time
      to exhaustion also increased in CR from 130 +/- 7 to 141 +/- 7 s (p < .01) and
      remained increased for another 7 days (139 +/- 8 s, p < .01). These data
      demonstrate that ingesting creatine monohydrate for 5 days increases the MAOD,
      and is likely to have an ergogenic effect on supramaximal exercise performance
      that persists for at least a week after treatment.

PMID- 9189304
TI  - Hormonal responses of multiset versus single-set heavy-resistance exercise
      protocols.
AB  - The purpose of this study was to compare serum growth hormone (GH), testosterone
      (T), cortisol (C), and whole blood lactate (L) responses to single set (1S)
      versus multiple set (3S) heavy-resistance exercise protocols. Eight
      recreationally weight-trained men completed two identical resistance exercise
      workouts (1S vs. 3S). Blood was obtained preexercise (PRE), immediately
      postexercise (OP), and 5 min (5P), 15 min (15P), 30 min (30P) and 60 min (60P)
      postexercise and was analyzed for GH, T, C, and L levels. For 1S and 3S, GH, L,
      and T significantly increased from PRE to OP and remained significantly elevated
      to 60P, except for 1S. For GH, T, and L, 3S showed significantly greater
      increases compared to 1S. For C, 3S and 1S were increased significantly from
      resting at OP, 5P, and 15P; 3S increased compared to 1S at 5P, 15P and 30P.
      Higher volumes of total work produce significantly greater increases in
      circulating anabolic hormones during the recovery phase following exercise.

PMID- 9189305
TI  - The pattern of breathing following a 10-breath voluntary hyperventilation during
      hyperoxic rebreathing.
AB  - The pattern of breathing following a 10-breath voluntary hyperventilation period
      during hyperoxic rebreathing was compared to that without hyperventilation in 6
      subjects (3 male and 3 female). The aim was to measure the posthyperventilation
      short-term potentiation of ventilation without changes in respiratory chemoreflex
      drives induced by the voluntary hyperventilation. Hyperoxia was used to reduce
      the peripheral chemoreflex drive, and rebreathing to prevent the decrease in
      arterial carbon dioxide tension normally produced by hyperventilation. There were
      significant differences between the male and female responses. However, in all
      subjects, ventilation and heart rate were increased during hyperventilation but
      end-tidal partial pressures of carbon dioxide and oxygen were unchanged.
      Following hyperventilation, ventilation immediately returned to the values
      observed when hyperventilation was omitted. Hyperventilation did not induce a
      short-term potentiation of ventilation under these conditions; changes in
      chemoreflex stimuli brought about by cardiovascular changes induced by
      hyperventilation may play a role in the short-term potentiation observed under
      other circumstances.

PMID- 9189306
TI  - Preexercise sugar feeding does not alter prolonged exercise muscle glycogen or
      protein catabolism.
AB  - The purpose of this study was to determine the effects of type of preexercise
      sugar feedings (glucose [GLU] or fructose [FRU]) on muscle glycogen and protein
      catabolism during prolonged exercise in fed men. Seven men cycled to exhaustion
      on three different occasions at 70% VO2max, 45 min after ingestion (700 ml) of
      either a 0.476 mol.L.1 carbohydrate (CHO) solution or a sweetened placebo (PLA).
      With GLU, serum insulin was significantly increased prior to exercise. As a
      result, serum glucose was significantly lower at 15 and 30 min of exercise with
      GLU, but was similar to the other treatments thereafter. Time to fatigue was
      absolutely longer with the GLU feeding, and exercise muscle glycogen catabolism
      was absolutely lower during the FRU trial, but the observed differences did not
      attain statistical significance due to intersubject variability. Protein
      catabolism was similar for all treatments. These data indicate that a 60-g
      preexercise glucose or fructose feeding following CHO loading procedures has
      minimal effects on muscle glycogen or protein catabolism during prolonged
      exercise.

PMID- 9189307
TI  - Effect of exercise intensity on free tryptophan to branched-chain amino acids
      ratio and plasma prolactin during endurance exercise.
AB  - The potential of exercise-induced changes in peripheral amino acids to alter
      blood prolactin levels through a serotonergic system modification was
      investigated in 8 male athletes. In two trials, subjects (N = 8) exercised on a
      cycle ergometer for 5 hr. The intensity of exercise corresponded to 55% VO2max
      (T55) or 75% VO2max (T75), respectively. In each trial, each subject received a
      25-g energy bar (111 kcal) every 60 min, as well as 300 ml of a 6% carbohydrate
      solution (90 kcal) every 30 min of exercise duration. Plasma glucose and insulin
      declined (p < or = .05) in both trials during exercise. Ammonia was augmented (p
      < or = .05) above the baseline concentration after 120 min in both trials. During
      the last 2 hr of exercise, plasma free fatty acids were higher (p < or = .05) in
      T75 than in T55. During this time, the plasma free TRP/BCAA ratio was also
      augmented (p < or = .05) in T75, while no change was induced in T55. Plasma
      prolactin did not change in T55, while an increase (p < or = .05) was found in
      T75. The findings may further support the hypothesis that during endurance
      exercise changes in peripheral amino acid concentration may influence prolactin
      response via serotonergic system modifications.

PMID- 9189614
TI  - Tooth morphogenesis and the differentiation of ameloblasts.
AB  - All vertebrate organs are formed from several cell types, and it is currently
      believed that interactions between the different components constitute the most
      important mechanism in the regulation of organ morphogenesis. In developing teeth
      morphogenetic interactions occur between the epithelium covering the facial
      processes and the underlying neural crest-derived mesenchyme. Morphogenesis is
      accompanied by differentiation of the various dental cell types, including the
      ameloblasts. Although ameloblasts differentiate terminally and start the
      deposition of enamel matrix only after the completion of crown morphogenesis,
      there is increasing evidence suggesting that the segregation of the ameloblast
      cell lineage may start much earlier. For example, the down-regulation of the
      North receptor, which in some other developmental system is associated with cell
      fate determination, is already seen in the dental epithelium prior to the bud
      stage. It is not known to what extent the differentiation of ameloblasts depends
      on tooth morphogenesis, and whether the same mesenchymal signals regulate
      morphogenesis and cell differentiation. There is evidence that growth factors act
      as morphogenetic signals. Bone morphogenetic proteins and fibroblast growth
      factors appear to regulate the initiation of tooth development, as well as the
      morphogenesis of the crown shape. However, the molecular nature of the signals
      regulating the advancing specialization of the cells in the ameloblast cell
      lineage remains unknown.

PMID- 9189615
TI  - Microstructure of enamel.
AB  - Enamel is a composite material consisting of mineral and organic phases. The
      properties of the mineral phase are modulated dramatically by its division into
      microscopic crystals, cemented together by the organic matrix protein polymer. A
      good concept of the 3D orientations of the crystals derives from visualizing
      their growth perpendicular to the surface in which they develop, which is pitted
      by the secretory poles of the ameloblasts. The arrangement of the crystals is the
      cause of the discontinuities, known as the prism boundaries or junctions, in the
      otherwise continuous structure. These locations acquire a more concentrated
      organic matrix during maturation, and they are both crack stoppers and crack
      propagation tracks in the adult tissue. Any tendency of prisms to cleave may be
      reduced by their varicosities, which reflect daily variations in the rate of
      production; their cross-sectional shape; the non-parallelism of adjacent groups,
      which develops through translocation of groups of cells across the surface during
      development; and the support of any one microscopic tissue element by other
      tissue, including dentine, placed to resist an applied load. Incremental growth
      lines are preferential cleavage planes within the enamel. Failure patterns of
      enamel in normal and abnormal use can be explained by these parameters, with
      additional consideration of functional variation and fatigue.

PMID- 9189616
TI  - Structure and function of secretory ameloblasts in enamel formation.
AB  - Secretory ameloblasts have multiple functions including the synthesis and
      resorption of enamel matrix proteins and calcium transport during enamel
      formation. We have examined these functions by means of cytochemistry and
      immunocytochemistry. Enamel proteins, amelogenins and enamelins are localized in
      the biosynthetic pathways of ameloblasts and in the forming enamel. Sulfated
      glycoconjugates are present in secretory ameloblasts. The distal junctional
      complex of ameloblasts may act as a permeability barrier to enamel proteins,
      thereby confining the secreted proteins to the growing enamel front. Secretory
      ameloblasts contain lysosomal enzymes in the Golgi lysosome endoplasmic reticulum
      system and also exhibit absorptive capacity, which might be associated with an
      early decrease in extracellularly degraded enamel proteins. Active calcium
      transport through the ameloblasts towards the growing enamel is indicated by the
      demonstration of Ca-ATPase activity along the plasma membranes. A calcium
      dependent modulator protein, calmodulin, is localized in ameloblasts, suggesting
      that early enamel mineralization is dependent upon calmodulin-regulated Ca-ATPase
      in ameloblasts. These results suggest that the secretory ameloblast is a highly
      specialized multifunctional cell in the production, resorption and degradation of
      enamel matrix and in the active calcium transport essential for matrix
      mineralization during enamel formation.

PMID- 9189617
TI  - Structure, crystal chemistry and density of enamel apatites.
AB  - The apatitic calcium phosphate crystals in dental enamel are too small for single
      crystal diffraction studies so the only possible direct structure determination
      must use whole-pattern-fitting Rietveld analysis of X-ray and neutron powder
      diffraction patterns. As a result, aspects of the structure are not known in
      detail. Further structural information can be obtained by consideration of
      published chemical analyses and infrared studies, taking into account studies of
      the crystal chemistry of synthetic apatitic analogues of enamel apatite. The
      apatitic constitutional water and total water content of enamel are particularly
      important, but there are difficulties in their determination. Making reasonable
      assumptions, a number of models of the unit cell can be derived. The weight per
      cent (including constitutional water) and density of the enamel apatite crystals
      for the most probable model are about 98 wt.% and 3.0 g cm-3, respectively. The
      apatite volume per cent calculated from these values is about 96%. The weight per
      cent and volume per cent of enamel apatite are higher than normally accepted
      values because of inclusion of constitutional water and use of a density for
      enamel apatite that takes into account its known lattice expansion over
      hydroxyapatite and probable lattice vacancies.

PMID- 9189618
TI  - Molecular strategies of tooth enamel formation are highly conserved during
      vertebrate evolution.
AB  - The vertebrate body plan is determined by a variety of morphoregulatory genes
      that are highly conserved throughout evolution. This review presents a
      phylogenetic analysis of selected molecular and morphological features in
      vertebrates with particular emphasis upon the phylogeny of tooth morphogenesis
      and enamel formation. Three lines of evidence support our hypothesis that the
      agnathans (e.g. hagfishes) are the most primitive extant vertebrates and that
      enamel gene products are highly conserved during vertebrate evolution. First, an
      antibody raised against the polypeptide produced by exon 4 of the mouse
      amelogenin gene recognizes proteins in hagfish, sharks, reptiles and mammals.
      Second, electron photomicrographic evidence suggests heterochronic shifts in the
      relative time and rate of enamel formation during vertebrate tooth evolution.
      Third, mRNA phenotyping suggests significant homology between amelogenin
      transcripts expressed in species of various vertebrate phyla including agnathans
      and mammals. These three lines of evidence indicate that amelogenin gene products
      are expressed in agnathan, reptilian and mammalian teeth.

PMID- 9189619
TI  - The protein composition of normal and developmentally defective enamel.
AB  - The development of human enamel involves a complex series of events including the
      secretion and degradation of a unique extracellular matrix. Ameloblasts progress
      through a succession of cellular phenotypes executing specialized secretory and
      regulatory functions. When performing optimally, ameloblasts produce a highly
      structured and mineralized tissue. Given the elaborate developmental events
      required for normal enamel formation, it is not surprising that a variety of
      enamel malformations arise from defects in matrix synthesis, secretion and
      extracellular processing. Normal matrix secretion and post-secretory processing
      by ameloblasts can be affected by a variety of hereditary and environmental
      conditions. These disturbances can result in an abnormal amount and/or
      composition of matrix proteins, and subsequently, an altered enamel structure
      and/or mineral content. For example, abnormal matrix removal during enamel
      maturation apparently contributes to hypomineralization associated with dental
      fluorosis. Incomplete matrix removal can also occur in several different forms of
      the hereditary condition amelogenesis imperfects. Specific types of this
      condition can have retention of substantial enamel protein (e.g. 5% by weight)
      that is, at least in part, composed of amelogenin and/or its breakdown products.
      Characterization of the enamel proteins in teeth affected by developmental
      disturbances can provide insight into the pathogenesis and normal formation of
      this highly specialized tissue.

PMID- 9189620
TI  - Extracellular matrix proteins of dentine.
AB  - Bone and dentine extracellular matrix proteins are similar, consisting primarily
      of type I collagen, acidic proteins and proteoglycans. Although collagen forms
      the lattice for deposition of calcium and phosphate for formation of carbonate
      apatite, the non-collagenous proteins are believed to control initiation and
      growth of the crystals. Despite this similarity, dentine contains three unique
      proteins apparently absent from bone and other tissue: dentine phosphophoryn
      (DPP), dentine matrix protein 1 (DMP1) and dentine sialoprotein (DSP). DPP and
      DMP1 are acidic phosphoproteins probably involved in the control of
      mineralization processes. DPP may localize in gap regions of collagen and
      initiate apatite crystal formation by binding large quantities of calcium in a
      conformation that promotes this process. Extensive studies have been conducted in
      our laboratory on the nature, biosynthesis, localization and gene structure of
      DSP. Immunolocalization studies showed that rat DSP, a 53 kDa sialic acid-rich
      glycoprotein, was synthesized by young and mature odontoblasts, and by dental
      pulp cells and pre-ameloblasts, but not by ameloblasts, osteoblasts, chondrocytes
      or other cell types. The cDNA sequence indicated that DSP was a 366-residue
      protein with several potential N-glycosylation sites, as well as phosphorylation
      sites, but that the amino acid sequence was dissimilar to that of other known
      proteins. Northern blot analysis detected several mRNA species near 4.6 and 1.5
      kb, indicative of alternative splicing events. Evidence for two DSP genes was
      obtained, further complicating this picture. Recent in situ hybridization studies
      utilizing rat and mouse molars and incisors indicated that DSP mRNA was expressed
      by young odontoblasts and odontoblasts in animals of all ages. Transcripts were
      also observed in pre-ameloblasts. The expression of DSP mRNA ceased when these
      cells matured to become secretory ameloblasts. DSP transcripts were not detected
      in osteoblasts or other cell types. The transient expression in pre-ameloblasts
      suggests a role of epithelial-mesenchymal interactions in the formation of the
      tooth.

PMID- 9189621
TI  - Amelogenin proteins of developing dental enamel.
AB  - The amelogenins of developing dental enamel are tissue-specific proteins, rich in
      proline, leucine, histidine and glutamyl residues, and synthesized by the
      ameloblast cells of the inner enamel epithelium. These proteins comprise the bulk
      of the extracellular matrix that becomes mineralized with a hydroxyapatite phase
      to become the mature enamel. Examination of the amino acid sequences of
      amelogenins from a range of mammals shows a high degree of evolutionary sequence
      conservation, suggestive of specialized function. Recently it has been shown that
      multiple amelogenin components, observed in the matrix, arise both by a sequence
      of post-secretory proteolytic processing and by the expression of alternatively
      spliced mRNAs generated from the amelogenin gene(s) that are located on the sex
      chromosomes. Although the function of these amelogenins in enamel
      biomineralization is unknown, physico-chemical studies of recombinant amelogenins
      have shown that they undergo a self-assembly process in vitro generating supra
      molecular 'nanosphere' structures, and recent observations in vivo point to a
      functional role for the nanospheres in the ultrastructural organization of the
      secretory enamel matrix, conducive to the organized development of the earliest
      mineral crystallites.

PMID- 9189622
TI  - Tuftelin: enamel mineralization and amelogenesis imperfecta.
AB  - Tuftelin is a novel acidic enamel protein thought to play a major role in enamel
      mineralization. Its identity and localization has been confirmed by amino acid
      composition, enzyme-linked immunosorbant assay, Western blots, indirect
      immunohistochemistry and high resolution protein-A gold immunocytochemistry. The
      deduced tuftelin protein (pI 5.2) contains 389 amino acids and has a calculated
      peptide molecular mass of 43,814 Da. Immunological studies suggest conservation
      of tuftelin structure between species throughout vertebrate evolution. The cDNA
      sequence encodes for several putative post-translation sites including one N
      glycosylation consensus site, seven O-glycosylation sites and seven
      phosphorylation sites, as well as an EF-hand calcium-binding domain (with
      mismatch), localized towards the N-terminal region. At the C-terminal region
      (residues 252-345) tuftelin contains structurally relevant determinants for self
      assembly. We recently cloned and partially sequenced the human tuftelin gene
      (four exons have now been sequenced). These sequences include exon 1 and over
      1000 bases of the putative promoter region. Employing fluorescent in situ
      hybridization, we mapped the human tuftelin gene to chromosome 1q 21-31.
      Localization of the human tuftelin gene to a well-defined cytogenetic region may
      be important in understanding the aetiology of autosomally inherited amelogenesis
      imperfecta, the most common enamel hereditary disease.

PMID- 9189624
TI  - Inherited enamel defects.
AB  - This paper describes the clinical, histological and genetic findings in
      individuals with amelogenesis imperfecta diagnosed in more than 50 families in
      the county of Vasterbotten, northern Sweden. Using pedigree analysis, families
      with autosomal and X-linked inheritance as well as sporadic cases of amelogenesis
      imperfecta have been recognized. A clinical subclassification in eight different
      variants of amelogenesis imperfecta has been made. The gene defects have been
      identified for two of these variants and the chromosomal location has been
      established for a third variant.

PMID- 9189623
TI  - Enamel maturation.
AB  - Enamel maturation is characterized by massive crystal growth in both width and
      thickness, resulting in the most highly mineralized of all mammalian skeletal
      tissues. The control of this process is mediated via a carefully orchestrated
      series of events that are temporally and spatially regulated, and it requires the
      co-ordinated degradation and removal of the endogenous enamel matrix. This is
      affected by both neutral metalloproteases and serine proteases, which are
      developmentally restricted and may be further modulated by changes in the
      chemistry of the enamel crystals themselves. Failure of these mechanisms, or the
      adventitious entry of mineral-binding proteins during the later stages of
      maturation, may result in the incomplete maturation of the enamel crystals and
      the eruption of dysplastic tissue.

PMID- 9189625
TI  - Regulation of amelogenin gene expression.
AB  - The amelogenins are found uniquely in enamel, where they constitute the
      predominant class of secreted matrix proteins and where they play a fundamental
      role in normal enamel formation. To better understand the high level of tissue
      specific expression, we cloned the bovine X and Y chromosomal amelogenin genes
      and the murine amelogenin gene and determined the DNA sequences for the regions
      upstream of the transcription start sites. We observed segments of strong
      homology among species, and identified consensus sequences for the binding of
      various transcription factors, including the glucocorticoid receptor, AP1, RXR
      and p53. Although specific sis-elements conferring enhanced transcription have
      not yet been identified, elements have been localized that have silencing effect
      in non-ameloblast cells. Conserved sequences are likely to be involved in tissue
      specific expression. Transgenic mouse studies have shown that 3.5 kb of upstream
      region is sufficient but 900 bp is insufficient for specific expression in vivo.
      Alternative splicing of the primary transcript is an effective mechanism for
      generating molecular heterogeneity. Amelogenin genes contain seven exons, and
      exons 3, 4, 5 and most of 6 can be deleted by alternative splicing. However, the
      pattern of exon splicing varies according to the species, and skipping of bovine
      exon 3 appears to be developmentally regulated. It will be important to determine
      whether the relative amounts of translation products differ among species as do
      the mRNAs, and to correlate the various protein structures with function. These
      findings also suggest that the regulation of amelogenin gene expression is
      complex and takes place at several levels.

PMID- 9189626
TI  - Molecular biology of hereditary enamel defects.
AB  - Amelogenesis imperfecta is a disfiguring inherited condition affecting tooth
      enamel. X-Linked and autosomal dominant and recessive inheritance patterns occur.
      X-Linked amelogenesis imperfecta has been studied extensively at the molecular
      level. Linkage analysis has shown that there is genetic hetetogeneity in X-linked
      amelogenesis imperfecta with two identified loci: AIH1 and AIH3. The AIH1 locus
      corresponds to the location of the amelogenin gene on the distal short arm of the
      X chromosome; various mutations in the amelogenin gene have been found in
      families with X-linked amelogenesis imperfecta. The AIH3 locus maps to the Xq24
      q27.1 region on the long arm of the X chromosome. Linkage to the long arm of
      chromosome 4 has been established in three families with autosomal dominant
      amelogenesis imperfecta. There is as yet no published evidence for genetic
      heterogeneity in autosomal dominant amelogenesis imperfecta as in X-linked
      amelogenesis imperfecta. Candidate genes for autosomal dominant amelogenesis
      imperfecta include tuftelin (1q), albumin (4q) and ameloblastin (4q) but the
      involvement of these genes in the disease has yet to be demonstrated. In view of
      the variable clinical appearances within families with autosomal dominant
      amelogenesis imperfecta and X-linked amelogenesis imperfecta, together with the
      finding that different X-linked amelogenesis imperfecta phenotypes result from
      mutations within the same gene, an alternative classification based on the
      molecular defect and mode of inheritance rather than phenotype has been proposed.

PMID- 9189627
TI  - Environmental causes of enamel defects.
AB  - A large number of causes of enamel defects, both environmental and genetic, have
      been described. However, many of these are derived from case histories and
      studies of individual conditions. What is needed now is a systematic
      investigation of the problem. The first requirement in exploring the aetiology
      further is the standardization of both the clinical diagnosis and the descriptive
      terminology. This has been provided by the Federation Dentaire Internationale
      Developmental Defects of Enamel Index. Comparing studies using standardized
      methods, including this index, has highlighted areas for closer investigation.
      The total prevalence of enamel defects in a population needs to be established as
      a baseline for studies on aetiology. Sixty-eight per cent of 1518 school children
      in London have enamel defects in the permanent dentition, with 10.5% having 10 or
      more teeth affected and 14.6% having hypoplasia, i.e. missing enamel. These
      findings are in contrast to the 37% with hypoplasia found in a group of third to
      fifth century Romano-Britons from Dorset, England, suggesting further
      consideration of possible environmental and genetic differences between the two
      populations. An overall long-term study of dental development in low birth weight
      children has shown significantly more (P < 0.001) enamel defects related to major
      health problems during the neonatal period. By using standardized, reproducible
      criteria in prevalence studies to gain an overview of the problem and then
      studying specific groups or conditions, it is possible to identify general and
      specific factors in the aetiology of enamel defects and investigate further the
      varying role of genetic and environmental effects.

PMID- 9189629
TI  - The role of enamel matrix proteins in the development of cementum and periodontal
      tissues.
AB  - The role of Hertwig's epithelial root sheath (HERS) and of the enamel-related
      proteins in the development of acellular cementum are reviewed. The inner layer
      of HERS is an apical extension of the ameloblastic layer in the crown. A number
      of studies now indicate that the cells of HERS have a secretory stage similar to
      the ameloblasts. In rats and mice the secretory product of the HERS cells does
      not seem to be amelogenin, which is the main protein of the enamel matrix. In
      humans, however, amelogenin has been demonstrated at the apical ends of the roots
      of developing teeth. The development and distribution of coronal cementum in
      various species are discussed. The amelogenins have been remarkably well
      conserved between species. Experiments in monkeys have shown that it is possible
      to induce formation of acellular cementum by application of porcine enamel matrix
      on a denuded root surface, which thereby promotes periodontal regeneration. These
      results further support the idea that enamel-related proteins are involved in
      cementum formation.

PMID- 9189628
TI  - Determinants and mechanisms of enamel fluorosis.
AB  - Enamel fluorosis occurs when fluoride concentrations in or in the vicinity of the
      forming enamel are excessive during its pre-eruptive development. Fluoride
      concentrations in plasma, enamel and other tissues reflect the difference between
      intake and excretion, i.e. fluoride balance. In addition to the diet, modern
      sources of ingested fluoride include a variety of dental products, some of which
      have been identified as risk factors for fluorosis. Fluoride absorption is
      inversely related to dietary calcium which, at high concentrations, may cause net
      fluoride secretion into the gastrointestinal tract. The excretion of absorbed
      fluoride occurs almost exclusively via the kidneys, a process which is directly
      related to urinary pH. Thus, fluoride balance and tissue concentrations and the
      risk of fluorosis are increased by factors such as high protein diets, residence
      at high altitude, and certain metabolic and respiratory disorders that decrease
      pH. Factors that increase urinary pH and decrease the balance of fluoride include
      vegetarian diets, certain drugs and some other medical conditions. Although
      several other fluoride-induced effects might be involved in the aetiology of
      fluorosis, it now appears that inhibition of enzymatic degradation of
      amelogenins, which may delay their removal from the developing enamel and impair
      crystal growth, may be of critical importance. In addition to the effects of
      fluoride, disturbances in enamel formation that can be confused with fluorosis
      are caused by chronic acidosis and hypoxia independently of the level of fluoride
      exposure.

PMID- 9189631
TI  - Antibiotic resistance: an ecological imbalance.
AB  - Antibiotic resistance thwarts the treatment of infectious diseases worldwide.
      Although a number of factors can be identified which contribute to the problem,
      clearly the antibiotic as a selective agent and the resistance gene as the
      vehicle of resistance are the two most important, making up a 'drug resistance
      equation'. Both are needed in order for a clinical problem to arise. Given
      sufficient time and quantity of antibiotic, drug resistance will eventually
      appear. But a public health problem is not inevitable if the two components of
      the drug resistance equation are kept in check. Enhancing the emergence of
      resistance is the case by which resistance determinants and resistant bacteria
      can spread locally and globally, selected by widespread use of the same
      antibiotics in people, animal husbandry and agriculture. Antibiotics are societal
      drugs. Each individual use contributes to the sum total of society's antibiotic
      exposure. In a broader sense, the resistance problem is ecological. In the
      framework of natural competition between susceptible and resistant bacteria,
      antibiotic use has encouraged growth of the resistant strains, leading to an
      imbalance in prior relationships between susceptible and resistant bacteria. To
      restore efficacy to earlier antibiotics and to maintain the success of new
      antibiotics that are introduced, we need to use antibiotics in a way which
      assures an ecological balance that favours the predominance of susceptible
      bacterial flora.

PMID- 9189630
TI  - The biomimetics of enamel: a paradigm for organized biomaterials synthesis.
AB  - The formation of enamel takes place through a sequence of processes that can be
      mimicked in inorganic materials chemistry. This chapter describes the generic
      features of enamel biomineralization in terms of a house-building analogy. Four
      stages are identified: supramolecular preorganization and spatial patterning;
      interfacial molecular recognition in inorganic nucleation; vectorial
      crystallization; and pattern evolution and hierarchy. Each of these concepts can
      be translated into synthetic approaches to the formation of inorganic materials
      with organized architectures. An example of applying this biomimetic paradigm is
      described. Supersaturated water-in-oil microemulsions have been used to
      synthesize microskeletal calcium phosphates by controlled nucleation and
      vectorial growth in constrained reaction environments. The results of these
      preliminary studies suggest that biomimetic concepts could be useful in the
      fabrication of biomaterial implants with controlled porosity and microstructure.

PMID- 9189632
TI  - Origins, acquisition and dissemination of antibiotic resistance determinants.
AB  - Since the introduction of antibiotics in the late 1940s there has been an
      inexorable propagation of antibiotic resistance genes in bacterial pathogens (and
      their relatives). This survival phenomenon was first characterized as the
      appearance of point mutations that altered drug targets, but in the mid-1950s
      transmissible antibiotic resistance genes were reported in Japan. Since this time
      both resistance strategies have been used, often in concert. For some types of
      antibiotic, only resistance by mutation has been identified, for others only
      resistance by plasmid acquisition. There is conflicting evidence with respect to
      the presence of antibiotic resistance in bacterial pathogens in the 'pre
      antibiotic' era; however, it is likely that the evolution of antibiotic
      resistance occurred over short periods. Thus, antibiotic resistance gene must be
      common in the environment, but their derivation remains to be established
      conclusively. This paper examines the proposals that antibiotic resistance genes
      originated in the bacterial population, either as bona fide resistance genes or
      genes encoding metabolic functions. In addition, the acquisition of heterologous
      resistance determinants by different genetic elements, their intergeneric
      exchange mechanisms, and the possible roles of antibiotics in the processes are
      discussed. Are there prospects for drug intervention that eliminate or retard
      these natural evolutionary processes?

PMID- 9189633
TI  - The relationship between erythromycin consumption and resistance in Finland.
      Finnish Study Group for Antimicrobial Resistance.
AB  - Because the discovery of new antimicrobial agents cannot be expected in the near
      future, we will have to manage with the antimicrobials currently available at
      least for the next decade or two. Therefore, attempts to prevent development of
      antimicrobial resistance are of major importance. The relationship of local
      antimicrobial consumption and antimicrobial resistance has been shown in many
      hospital studies but not in the community, even though this is where most
      antibiotics are used. At the beginning of 1990s, erythromycin resistance in group
      A streptococci increased rapidly in Finland. The geographical variations found
      led to a nationwide study of the possible relation between local erythromycin
      consumption and variations in erythromycin resistance in the community.
      Erythromycin resistance was found to be significantly (P = 0.006) linked to local
      consumption of erythromycin. In further experiments, we found that a new
      erythromycin resistance phenotype belonging to the T4 serotype was spread over
      the whole country; 83% of the erythromycin-resistant isolates were of this new
      phenotype in 1994. In 1991, recommendations were given to reduce use of
      erythromycin in Finland. Following these recommendations, macrolide consumption
      decreased by 40% from 1991-1994. Studies are now in progress to evaluate the
      effect of this reduction on erythromycin resistance of group A streptococci.

PMID- 9189634
TI  - The contribution of antibiotic use on the frequency of antibiotic resistance in
      hospitals.
AB  - Abundant evidence suggests a relationship between antibiotic resistance and use,
      including animal models, consistent associations between resistance and
      antibiotic use in hospitals, concomitant variation in resistance as antibiotic
      use varies, and a dose-response relationship for many pathogen/antibiotic
      combinations. Much of the evidence has come from studies performed in single
      hospitals. Most multicentre studies on resistance have not included data on
      antibiotic usage. Despite this substantial body of evidence, some studies have
      failed to demonstrate an association between antibiotic resistance and use,
      suggesting other contributing factors such as cross-transmission, inter-hospital
      transfer of resistance, a community contribution to resistance, or a complex
      relationship between resistance and the use of a variety of antibiotics. A
      multicentre study, project ICARE (Intensive Care Antimicrobial Resistance
      Epidemiology), implemented in 1994 by Centers for Disease Control and Prevention
      and Rollins School of Public Health, Emory University, has found dramatic
      differences in the patterns of antibiotic usage and resistance in US hospitals.
      The findings suggest that antibiotic usage is the major risk factor in
      development of antibiotic resistance in hospitals but the relationship can be
      complex with additional factors involved. Understanding the problem of antibiotic
      resistance in a hospital cannot be achieved without knowledge of the hospital's
      pattern of antibiotic use.

PMID- 9189635
TI  - Impact of antibiotic use in animal feeding on resistance of bacterial pathogens
      in humans.
AB  - With the exception of flavomycin and olaquindox, the antibiotics currently used
      in European countries as feed additives exert a Gram-positive spectrum of
      activity. Of these, tylosin and virginiamycin are known for cross-resistance to
      macrolides, lincosamidines and streptogramines, and avoparcin is known for cross
      resistance to vancomycin and teicoplanin. The use of avoparcin in animal
      husbandry creates a potential reservoir of transferable, vanA-mediated
      glycopeptide resistance in enterococci. A study in a rural area in Germany where
      vancomycin-resistant enterococci (VRE) were not isolated from infected humans but
      found in animal husbandry has shown that VRE are disseminated via meat products
      and are also found in faecal samples of non-hospitalized humans. VRE of different
      ecological origin from Germany (hospitals, sewage, food, animal husbandry) are
      polyclonal as evidenced by macrorestriction patterns and multilocus enzyme
      electrophoresis, suggesting a wide dissemination of the vanA gene cluster. These
      results confirm earlier observations on the spread of the sat genes, which confer
      resistance to a streptothricin antibiotic which has only been used in animal
      feeding. The resistance determinants were later also found in Escherichia coli
      from human infections and had spread in the absence of selective pressure.

PMID- 9189636
TI  - The effect of monitoring of antibiotic use on decreasing antibiotic resistance in
      the hospital.
AB  - In Greece, antibiotic over-consumption and high resistance rates run in parallel.
      In the spring of 1989 surveillance of 12500 Gram-negative strains, derived from
      55 hospitals from all over Greece, revealed that resistance rates of Pseudomonas
      aeruginosa, Enterobacter spp., Klebsiella spp. and Acinetobacter spp. to
      antimicrobial agents introduced after 1985 exceeded 50%. As a consequence, the
      application of (1) rules of hospital hygiene, (2) educational small group
      programs, and (3) an antibiotic policy aiming to restrict antibiotic use, was
      decided in Laiko General Hospital. Since 1989, imipenem, the newer quinolones,
      vancomycin, aztreonam and third-generation cephalosporins were only ordered to
      the hospital pharmacy after completion of a specific request form, which since
      1991 has been more detailed and which can be signed only by physicians with
      interest in infectious diseases. In 1991, in cooperation with the pharmacy, an
      audit program was added requiring a final inspection of the already approved
      request forms by an infectious diseases specialist. Any disagreement was
      discussed with the physicians in charge. Consumption data were analysed monthly
      and discussed with each department. Newer antibiotic consumption in a selected
      month (November) of three consecutive years, before (1991) and after the
      application of the audit program (1992-1995) has been analysed. Results reveal a
      decrease in consumption of restricted antibiotics, especially in surgical
      departments and in kidney transplantation units, without simultaneous increase in
      consumption of the non-restricted compounds. Since 1994, resistance has decreased
      remarkably. However, the resistance of quinolones is increasing steeply.
      Consequently, for the last 12 months quinolones have been removed from the
      hospital formulary. An audit program requires close co-operation of physicians,
      pharmacists and, particularly, of surgeons, in the application of a correct
      prophylaxis regimen. It seems to be efficacious in reducing both resistance rates
      and total antibiotic consumption.

PMID- 9189637
TI  - The antibiotic selective process: concentration-specific amplification of low
      level resistant populations.
AB  - The biochemistry and genetics of antibiotic resistance are far better known than
      the equally important events underlying the selection of resistant populations.
      The hidden selection of low-level resistant variants may be a key process in the
      emergence of high-level antibiotic resistance. Different low-level resistant
      bacterial subpopulations may be specifically selected by different low antibiotic
      concentrations. The space in the environment (human body) where a given selective
      concentration exists represents the selective compartment. For pharmacokinetic
      reasons, low antibiotic concentrations occur in a larger selective compartment
      and persist longer than high antibiotic concentrations. The specific selection of
      low-level variants by low concentrations of antibiotic can be reproduced in
      experimental in vitro models using mixtures of susceptible and low-level
      resistant populations. We demonstrated this in Escherichia coli strains
      harbouring TEM-1, TEM-12 and TEM-10 beta-lactamases challenged by cefotaxime, and
      also Streptococcus pneumoniae strains with various levels of penicillin
      resistance challenged by amoxicillin or cefotaxime. In both cases, four hours of
      antibiotic challenge produced selective peaks of low-level resistant variant
      populations at low-level antibiotic concentrations. We conclude that variants
      with small decreases in antibiotic susceptibility may be fully selectable under
      in vivo circumstances; on the other hand, low-level antibiotic concentrations may
      have a considerable selective effect on the emergence of antibiotic resistance.

PMID- 9189638
TI  - The within-host population dynamics of antibacterial chemotherapy: conditions for
      the evolution of resistance.
AB  - For tuberculosis and number of other bacterial infections, treatment with a
      single antimicrobial drug frequently fails due to the ascent of mutants resistant
      to that drug. To minimize the likelihood of this occurrence, multiple drugs with
      independent resistance mechanisms are used simultaneously. None the less,
      multiply resistant bacteria sometimes emerge even when patients are
      simultaneously treated with two or more drugs, and the ascent of these multiply
      resistant mutants may result in treatment failure in the patient and spread of
      these resistant bacteria to other hosts. We consider two mathematical models of
      antibacterial chemotherapy which can account for the ascent of multiple
      antibiotic resistance within hosts treated with multiple antibiotics. In both,
      multiple resistance evolves because of selection favouring mutants resistant to
      fewer than all of the chemotherapeutic agents employed, intermediates. In one
      model, this occurs because of temporal fluctuations in the concentrations of the
      antibiotics in the course of normal treatment and/or because of non-adherence to
      the treatment regime. In the other, intermediates are favoured and multiple
      resistance evolves because of tissue and somatic cell heterogeneity. In the
      effective concentrations of the antibiotics and physiological variation in the
      sensitivity of subpopulations of bacteria to different antibiotics. We discuss
      the limitations (and assets) of this model and approach and the implications for
      the design of antibiotic treatment regimes. Finally, we consider how the
      assumptions behind this model and the predictions made from its analysis could be
      tested experimentally.

PMID- 9189639
TI  - The cost of antibiotic resistance--from the perspective of a bacterium.
AB  - The possession of an antibiotic resistance gene clearly benefits a bacterium when
      the corresponding antibiotic is present. But does the resistant bacterium suffer
      a cost of resistance (i.e. a reduction in fitness) when the antibiotic is absent?
      If so, then one strategy to control the spread of resistance would be to suspend
      the use of a particular antibiotic until resistant genotypes declined to low
      frequency. Numerous studies have indeed shown that resistant genotypes are less
      fit than their sensitive counterparts in the absence of antibiotic, indicating a
      cost of resistance. But there is an important caveat: these studies have put
      antibiotic resistance genes into naive bacteria, which have no evolutionary
      history of association with the resistance genes. An important question,
      therefore, is whether bacteria can overcome the cost of resistance by evolving
      adaptations that counteract the harmful side-effects of resistance genes. In
      fact, several experiments have shown that the cost of antibiotic resistance may
      be substantially diminished, even eliminated, by evolutionary changes in bacteria
      over rather short periods of time. As a consequence of this adaptation of
      bacteria to their resistance genes, it becomes increasingly difficult to
      eliminate resistant genotypes simply by suspending the use of antibiotics.

PMID- 9189640
TI  - The evolution of beta-lactamases.
AB  - beta-lactamases, the enzymes often associated with resistance to beta-lactam
      antibiotics, are found in most bacterial species. Although these enzymes
      protected bacteria from naturally occurring beta-lactams long before the
      introduction of synthetic antimicrobial agents, the numbers and varieties of beta
      lactamases have increased dramatically with the introduction of modern
      penicillins and cephalosporins. Over the past twenty years it has become apparent
      that families of beta-lactamases have been selected as the result of
      antimicrobial usage. Outbreaks of beta-lactam-resistant bacteria can be traced to
      the introduction of specific classes of beta-lactams or to the introduction of a
      specific agent. Many of the most serious epidemics can be related to transferable
      beta-lactamase genes that are harboured on multidrug-resistant plasmids. The
      separation of beta-lactamases into three major functional groups or four
      structural classes has been proposed. Stepwise selection of variants within
      several of these classes has been documented both in the clinical setting and in
      the laboratory, e.g. the extended-spectrum (TEM and SHV) beta-lactamases and the
      inhibitor-resistant (TEM) beta-lactamases. Close relationships among the recently
      described plasmid-mediated 'cephamycinases' and the common chromosomal
      cephalosporinases have been identified. Carbapenem-hydrolysing metallo-beta
      lactamases with broad spectrum hydrolysing activity have become serious concerns
      as they begin to be described on plasmids. Factors contributing to selection of
      beta-lactam-resistant strains include decreased outer membrane permeability and
      increased beta-lactamase production.

PMID- 9189641
TI  - Molecular evolution of multiply-antibiotic-resistant staphylococci.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an intractable nosocomial
      pathogen. The chemotherapeutic intransigence of this organism stems from its
      predilection to antimicrobial resistance as a consequential response to selective
      pressures prevailing in the clinical environment. MRSA isolates are frequently
      resistant to all practicable antimicrobials except the glycopeptide, vancomycin.
      Although antimicrobial resistance sometimes arises via chromosomal mutation, the
      emergence of multiply-antibiotic-resistant staphylococci is primarily due to the
      acquisition of pre-existent resistance genes; such determinants can be encoded
      chromosomally or by plasmids and are often associated with transposons or
      insertion sequences. Clinical staphylococci commonly carry one or more plasmids,
      ranging from small replicons that are phenotypically cryptic or contain only a
      single resistance gene, to larger episomes that possess several such determinants
      and sometimes additionally encode systems that mediate their own conjugative
      transmission and the mobilization of other plasmids. The detection of closely
      related plasmids, elements and/or genes in other hosts, including coagulase
      negative staphylococci and enterococci, attests to interspecific and intergeneric
      genetic exchange facilitated by mobile genetic elements and DNA transfer
      mechanisms. The extended genetic reservoir accessible to staphylococci afforded
      by such horizontal gene flux is fundamental to the acquisition, maintenance and
      dissemination of staphylococcal antimicrobial resistance in general, and
      multiresistance in particular.

PMID- 9189642
TI  - Mobile gene cassettes and integrons: moving antibiotic resistance genes in gram
      negative bacteria.
AB  - In Gram-negative pathogens, multiple antibiotic resistance is common and many of
      the known resistance genes are contained in mobile gene cassettes. Cassettes can
      be integrated into or deleted from their receptor elements, the integrons, or
      infrequently may be integrated at other locations via site-specific recombination
      catalysed by an integron-encoded recombinase. As a consequence, arrays of several
      different antibiotic resistance genes can be created. Over 40 gene cassettes and
      three distinct classes of integrons have been identified to date. Cassette
      associated genes conferring resistance to beta-lactams, aminoglycosides,
      trimethoprim, chloramphenicol, streptothricin and quaternary ammonium compounds
      used as antiseptics and disinfectants have been found. In addition, most members
      of the commonest family of integrons (class 1) include a sulfonamide resistance
      determinant in the backbone structure. Integrons are themselves translocatable,
      though most are defective transposon derivatives. Integron movement allows
      transfer of the cassette-associated resistance genes from one replicon to another
      or into another active transposon which facilitates spread of integrons that are
      transposition defective. Horizontal transfer of the resistance genes can be
      achieved when an integron containing one or more such genes is incorporated into
      a broad-host-range plasmid. Likewise, single cassettes integrated at secondary
      sites in a broad-host-range plasmid can also move across species boundaries.

PMID- 9189643
TI  - Genetic mobility and distribution of tetracycline resistance determinants.
AB  - Since 1953, tetracycline-resistant bacteria have been found increasingly in
      humans, animals, food and the environment. Tetracycline resistance is normally
      due to the acquisition of new genes and is primarily due to either energy
      dependent efflux of tetracycline or protection of the ribosomes from its action.
      Gram-negative efflux genes are frequently associated with conjugative plasmids,
      whereas Gram-positive efflux genes are often found on small mobilizable plasmids
      or in the chromosome. The ribosomal protection genes are generally associated
      with conjugative transposons which have a preference for the chromosome.
      Recently, tetracycline resistance genes have been found in the genera
      Mycobacterium, Nocardia, Streptomyces and Treponema. The Tet M determinant codes
      for a ribosomal protection protein which can be found in Gram-positive, Gram
      negative, cell-wall-free, aerobic, anaerobic, pathogenic, opportunistic and
      normal flora species. This promiscuous nature may be correlated with its location
      on a conjugative transposon and its ability to cross most biochemical and
      physical barriers found in bacteria. The Tet B efflux determinant is unlike other
      efflux gene products because it confers resistance to tetracycline, doxycycline
      and minocycline and has the widest host range of all Gram-negative efflux
      determinants. We have hypothesized that mobility and the environment of the
      bacteria may help influence the ultimate host range of specific tet genes. If we
      are to reverse the trend towards increasingly antibiotic-resistant pathogenic
      bacteria, we will need to change how antibiotics are used in both human and
      animal health as well as food production.

PMID- 9189644
TI  - Epidemiological factors influencing the emergence of antimicrobial resistance.
AB  - Antimicrobial resistance is becoming an important public health problem for both
      hospital- and community-acquired infections. In the hospital, infections caused
      by drug-resistant Staphylococcus aureus, Mycobacterium tuberculosis, enterococci,
      and a variety of Gram-negative rods are resulting in increased morbidity,
      mortality and costs, in part because of prolonged hospitalization and the use of
      more expensive antimicrobial agents. Drug-resistant, community-acquired
      infections are also causing important problems in both the developed and the
      developing world. Although the relative importance of specific pathogens varies
      with the geographical area, community-acquired pathogens including Salmonella,
      Shigella, Neisseria gonorrhoeae, Haemophilus influenzae and Streptococcus
      pneumoniae are causing both sporadic cases and outbreaks of drug-resistant
      illness. The emergence of antimicrobial resistance is being attributed to a
      series of societal, technological, environmental and microbial changes. These
      include increasing populations of susceptible hosts, international travel and
      commerce, changes in technology and industry, microbial adaptation and change,
      and the breakdown of public health measures. Addressing emerging problems and
      antimicrobial resistance will require enhanced surveillance, prudent use of
      existing antimicrobial drugs, development of new antimicrobial agents, increased
      emphasis on infection control and hygienic practices, effective disease control
      programs, better use of existing vaccines, and development of more and better
      vaccines.

PMID- 9189646
TI  - Factors influencing the estimation of the albumin excretion rate in subjects with
      diabetes mellitus.
AB  - OBJECTIVE: To evaluate alternative methods of calculating the albumin excretion
      rate (AER) in the absence of complete and accurate patient documentation, since
      microalbuminuria in patients with diabetes mellitus is associated with serious
      complications and since patients often make errors in recording the volume and
      timing of urine collection, making AER calculations inaccurate. DESIGN:
      Prospective study. SETTING: Recruitment sites, including all native reserves,
      across southern Alberta. PARTICIPANTS: Population-based group of 1286 subjects
      with diabetes mellitus participating in the Southern Alberta Study of Diabetic
      Retinopathy. INTERVENTIONS: Timed AERs were measured in the subjects; urinary
      albumin concentration was measured by radioimmunoassay. OUTCOME MEASURES: A
      formula for the prediction of AER was based on the clinical data from the
      subjects. Several factors were considered in developing the formula: insulin
      using status, weight, sex and urine and serum creatinine concentrations. RESULTS:
      A mathematical model for estimation of the AER was developed; incorporation of
      insulin use, sex and weight provides a more accurate estimate of AER. According
      to this model, women typically appear to have a lower AER than men and heavier
      people appear to have a higher AER than people with lower body weight.
      CONCLUSIONS: The use of mathematical formulae to calculate the AER provides an
      accurate estimate of the AER, particularly when data related to the volume and
      timing of urine collection are missing. These formulae will be valuable in large
      epidemiologic screening programs.

PMID- 9189645
TI  - Glucose turnover and gluconeogenesis during pregnancy in women with and without
      insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To characterize the effect of pregnancy on glucose turnover and
      gluconeogenesis in healthy women and in women with well-controlled insulin
      dependent diabetes mellitus (IDDM). DESIGN: Prospective clinical study. SETTING:
      Clinical research unit of the Hotel-Dieu de Montreal hospital. PARTICIPANTS: Five
      healthy pregnant women and 6 pregnant women with IDDM. INTERVENTIONS: Glucose
      turnover and gluconeogenesis in the postabsorptive state at 16 and 32 weeks'
      gestation and at 24 weeks postpartum were studied with the use of a double stable
      isotope technique (D[2,3,4,6,6(2)H]-glucose and L[1,2,3(13)C]-alanine). In the
      women with IDDM, plasma glucose levels were controlled by continuous subcutaneous
      insulin infusion throughout pregnancy and with a Biostator on the morning of the
      study. RESULTS: In the women without IDDM, hepatic glucose production was 11.6
      (standard error of the mean [SEM] 2.2) mumol/kg per minute at 16 weeks'
      gestation, 12.5 (SEM 1.8) mumol/kg per minute at 32 weeks' gestation, and 13.2
      (SEM 1.9) mumol/kg per minute at 24 weeks postpartum. In the women with IDDM, it
      was 10.7 (SEM 2.4) mumol/kg per minute, 10.5 (SEM 1.2) mumol/kg per minute and
      12.3 (SEM 0.5) mumol/kg per minute at the same respective periods. The difference
      in levels between the 2 groups was not significant. Levels of the gluconeogenic
      precursors alanine and lactate were increased during pregnancy in both the women
      without IDDM (from 0.18 [SEM 0.02] mmol/L and 0.64 [SEM 0.09] mmol/L,
      respectively, to 0.25 [SEM 0.02] mmol/L and 1.15 [SEM 0.17] mmol/L, respectively,
      p < 0.01) and in those with IDDM (from 0.15 [SEM 0.01] mmol/L and 0.47 [SEM 0.04]
      mmol/L, respectively, to 0.19 [SEM 0.02] mmol/L and 0.70 [SEM 0.01] mmol/L,
      respectively, p < 0.05). After an overnight fast, gluconeogenesis from alanine
      was not affected by pregnancy in both groups of women. In the women without IDDM,
      the plasma insulin level was low in early pregnancy (33.6 [SEM 3.6] pmol/L) and
      increased in late gestation (87.6 [SEM 9.6] pmol/L) compared with postpartum
      levels (60.0 [SEM 7.8] pmol/L). Plasma glucagon levels tended to rise in late
      gestation (from 95.1 [SEM 6.7] ng/L to 116.0 [SEM 36.0] ng/L). In the women with
      IDDM, the free plasma insulin and plasma glucagon levels were higher in early
      pregnancy (55.2 [SEM 6.6] pmol/L and 196.1 [SEM 29.8] ng/L, respectively) and did
      not change significantly during pregnancy. CONCLUSION: Basal glucose turnover and
      gluconeogenesis are not increased during pregnancy in women without IDDM or in
      women with well-controlled IDDM. The decrease in the plasma glucose level during
      pregnancy suggests that the use of glucose by the growing fetus is augmented and
      that this is not totally compensated for by a rise in postabsorptive hepatic
      glucose production. The glucose requirement by the growing fetus is probably
      supplied by the increased postprandial plasma glucose level.

PMID- 9189647
TI  - Effects of substituting dietary soybean protein and oil for milk protein and fat
      in subjects with hypercholesterolemia.
AB  - OBJECTIVES: To determine whether, in individuals with hypercholesterolemia,
      substituting dietary soybean products for cows' milk products improves the plasma
      lipid profile and whether any change in the profile is due partially to soy oil.
      DESIGN: Randomized 3-treatment crossover trial. SETTING: Family practice clinics
      and an outpatient clinic in London, Ont. PARTICIPANTS: Seventeen healthy men and
      17 healthy women with elevated plasma levels of total and low-density-lipoprotein
      (LDL) cholesterol and with normal plasma levels of triglycerides. INTERVENTIONS:
      Participants incorporated into their normal diet either 2% cows' milk products,
      soybean products or a combination of skim milk products and soy oil, each over
      period of 4 weeks, with 22-week wash-out periods. Plasma lipid profile, blood
      pressure and body weight were assessed after each dietary and wash-out period.
      OUTCOME MEASURES: Plasma levels of total and lipoprotein cholesterol, plasma
      levels of triglycerides, apolipoprotein B and A1 levels, blood pressure and
      plasma lipid peroxidation. RESULTS: The change in diet had no effect on body mass
      index, levels of apolipoproteins B and A1 and most plasma lipids. During the
      soybean period, the subjects' mean level of high-density-lipoprotein (HDL)
      cholesterol increased 9% (p < 0.04) and their mean LDL/HDL cholesterol ratio
      decreased 14% (p < 0.007). These effects were less pronounced during the skim
      milk/soy oil period. In the 24 subjects with the highest initial LDL cholesterol
      level and LDL/HDL cholesterol ratio, the mean LDL cholesterol level decreased 11%
      after the soybean period. In all subjects, changes in the LDL/HDL cholesterol
      ratio induced by a soybean diet were negatively correlated with the initial
      LDL/HDL cholesterol ratio and positively correlated with the initial HDL
      cholesterol level. CONCLUSIONS: In people with hypercholesterolemia, the plasma
      lipid profile improved after treatment with a soybean-product diet, and this
      improvement was partially due to soy oil. The degree of responsiveness was
      associated with initial risk factors for coronary artery disease.

PMID- 9189648
TI  - Acetylsalicylic acid (aspirin) test for the diagnosis of renovascular
      hypertension.
AB  - OBJECTIVE: To determine whether the administration of acetylsalicylic acid (ASA,
      also known as Aspirin) differentiates patients with renovascular hypertension
      from those with essential hypertension, in order to provide a simple alternative
      to more expensive forms of diagnosis for this condition. DESIGN: Trial of ASA
      test in patients with previously diagnosed essential and renovascular
      hypertension. SETTING: Inpatient department of an academic health sciences centre
      in Poznan, Poland. PATIENTS: Forty patients with essential hypertension and 21
      patients with renovascular hypertension. INTERVENTIONS: Patients were given an
      intravenous injection of ASA (10 mg/kg body weight), blood pressure was measured
      and blood was sampled and assayed for plasma renin activity (PRA) before and 30
      minutes after the injection. RESULTS: ASA infusion in patients with renovascular
      hypertension resulted in a decrease in PRA from 15.2 (standard deviation [SD]
      12.4) ng/mL per hour to 7.2 (SD 9.8) ng/mL per hour, whereas in patients with
      essential hypertension the initial PRA was significantly lower before ASA
      administration and did not change afterward. In patients with renovascular
      hypertension, the mean systolic, diastolic and arterial pressure decreased
      significantly (p < 0.001) after ASA infusion, but these did not change in
      patients with essential hypertension. Based on the criterion of 4 mm Hg as a
      detectable decrease in mean blood pressure, the sensitivity of the ASA test was
      95.0% and the specificity 82.5%; its positive predictive value was 74% and its
      negative predictive value 97%. CONCLUSION: The precise measurement of blood
      pressure during the ASA test may provide a useful method of differentiating
      between patients with renovascular and essential hypertension.

PMID- 9189649
TI  - Multimerin: a bench-to-bedside chronology of a unique platelet and endothelial
      cell protein--from discovery to function to abnormalities in disease.
AB  - In studies conducted about 8 years ago, the author and her colleagues raised a
      monoclonal antibody that recognized an uncharacterized human platelet protein
      with a reduced molecular mass of 155 kDa. Investigations of this protein's
      nonreduced structure yielded surprising findings: in its native state, it exists
      as massive disulfide-linked multimers millions of daltons in size, making it one
      of the largest proteins found in the human body. This feature led the author to
      designate this protein "multimerin." Multimerin is found in endothelial cells as
      well as in platelets. It originates from a single subunit protein, promultimerin,
      that undergoes extensive N-glycosylation, proteolytic processing and
      polymerization during biosynthesis. Recent data from the cloning and sequencing
      of its complementary DNA indicate that multimerin is a unique protein. Like von
      Willebrand factor, it has a massive repeating structure, but these proteins are
      unrelated. Multimerin's sequence contains the adhesive motif Arg-Gly-Asp-Ser,
      central coiled-coil sequences, several epidermal growth-factor-like motifs, and a
      globular domain that is similar to a protein-binding domain found in complement
      C1q and in collagens type VIII and X. Investigations of multimerin's function
      indicate that it binds the coagulation protein factor V and its activated form,
      factor Va. In platelets, but not in plasma, all of the biologically active factor
      V is complexed with multimerin. Multimerin may also have functions as an
      extracellular matrix or adhesive protein. Recently, members of 2 Canadian
      families with puzzling autosomal-dominant bleeding disorders were found to have a
      deficiency of platelet multimerin. Studies of these patients may provide a unique
      opportunity to evaluate the functions of multimerin.

PMID- 9189650
TI  - Clinical trials and tribulations: a personal view of interacting with
      pharmaceutical manufacturers.
AB  - As grants from agencies shrink, universities and academic researchers are
      pursuing work on clinical trials funded by pharmaceutical manufacturers. The
      author, an investigator with a nonprofit research cooperative, offers insight and
      advice on industry-sponsored trials. He finds that the "doorways" to industry
      research are hidden, as are industry priorities. Researchers with limited
      experience have trouble "breaking in" and, when they do work on industry
      sponsored trials, are usually given the less interesting work at first.
      Difficulties encountered during industry-sponsored trials include lack of
      researcher input, unreasonable enrolment requirements, delays by the sponsor and
      quashing of publication of unfavourable results. On the positive side, a good
      experience can include stimulating research, with the researcher playing a
      substantial role in all phases, an adequate budget, rapid turnaround and
      publication of the results. To succeed in this environment, trialists should have
      established expertise, technical and managerial abilities, appropriate resources
      and strong personal attributes; a national or international reputation is an
      asset. Researchers can benefit from universities' industry liaison offices and
      from strong oversight by institutional review boards.

PMID- 9189651
TI  - Bill C-91: the debate continues.

PMID- 9189652
TI  - Metabolism and toxicity of 2-methylpropene (isobutene)--a review.
AB  - 2-Methylpropene (MP) or isobutene is a gaseous chemical used on a large scale in
      the synthetic rubber industry. The present review covers the rather scarce
      literature on MP with respect to its metabolic fate and toxicity in laboratory
      animals and humans. It has been shown both in vivo and in vitro that MP is
      metabolized to the primary metabolite 2-methyl-1,2-epoxypropane (MEP) by rodent
      and human liver tissue. The formation of this reactive epoxide intermediate is
      catalyzed by CYP2E1, while epoxide hydrolase and glutathione S-transferase appear
      to be involved in its inactivation. In rats, the capacity to absorb and
      metabolize MP is saturable. MP is oxidized to compounds that are mainly excreted
      in urine. Data indicate that rodents can tolerate low levels of MP without
      apparent toxicity. The primary metabolite MEP, however, is able to produce
      genetic damage in both prokaryotic and eukaryotic cells in vitro. MP is thus not
      toxic per se but elicits metabolic activation to become potentially harmful.
      Consequently, the balance between formation and detoxification of MEP plays a key
      role in determining the potential toxicity of the parent compound. Obviously,
      further research, including repeated exposure toxicity studies, is required
      before an estimation of the risk for man can be made.

PMID- 9189653
TI  - Epidemiologic evidence on the relationship between mists containing sulfuric acid
      and respiratory tract cancer.
AB  - This review identified and evaluated 25 epidemiologic studies pertaining to the
      carcinogenicity of mists containing sulfuric acid (MSA). Few studies were
      designed with acid mists as the principal exposure under investigation, and in
      all studies exposure assessment was limited. The results of the follow-up studies
      from industries with high or moderate exposure potential and the case-control
      studies indicate, in aggregate, a moderate association between MSA and larynx
      cancer. The data suggest a dose-response relationship. However, many of the
      results from individual studies are imprecise, and confounding by smoking,
      alcohol, and other occupational agents is not adequately adjusted for. The
      biologic plausibility and the possible carcinogenic mechanism remain uncertain.
      There is little evidence in support of a causal relationship between exposure to
      MSA and lung cancer. Information is inadequate for drawing any meaningful
      inference about the association between exposure to MSA and nasal cancer.

PMID- 9189654
TI  - A review of the chronic toxicity, carcinogenicity, and possible mechanisms of
      action of inorganic acid mists in animals.
AB  - Occupational exposure to inorganic acid mists containing sulfuric acid has been
      associated with increased laryngeal cancer. The primary objective of this review
      was to compile the literature regarding chronic toxicity and carcinogenicity of
      inorganic acid mists in laboratory animals. Several chronic toxicity studies had
      exposures of 1 year or longer. Whereas numbers of animals were limited, no
      evidence of neoplastic or preneoplastic lesions was reported. Two studies
      evaluated the carcinogenicity of inorganic acid mists in rats; however, one was
      limited by a short duration of exposure and the other did not achieve a maximum
      tolerated dose. A large lifetime study in hamsters evaluated the carcinogenicity
      of 100 mg/M3 sulfuric acid mist, as well as its ability to act as a promoter or
      co-carcinogen for benzo(a)pyrene. No evidence of carcinogenic potential was
      shown. Although an increase in papillomas was noted in the benzo(a)pyrene + H2SO4
      group, the co-carcinogenic or promoting potential was considered equivocal. Thus,
      no evidence from experimental animals strongly supports or refutes the induction
      of cancer by inorganic acid mists. A possible mechanism that could be associated
      with inorganic acid mist carcinogenicity relates to the genetic consequences of
      lowering the pH. Reduced pH can induce chromosomal aberrations, enhance
      depurination, and deamination of cytidine in DNA. This mechanism has not been
      evaluated in tissues of the respiratory tract.

PMID- 9189655
TI  - Structural identifiability of PBPK models: practical consequences for modeling
      strategies and study designs.
AB  - Physiologically based pharmacokinetic (PBPK) models usually contain unknown
      parameters that need to be estimated by calibration to concentration-time
      profiles from in vivo experiments. However, even with error-free data, the number
      of parameters that can be estimated in this way is limited, depending on the
      particular situation. This paper introduces the concept of structural
      identifiability of a model, a requirement to make the estimation of parameters by
      calibration a meaningful undertaking. We briefly discuss the techniques-available
      from systems analysis-for examining the identifiability of models. Two conditions
      of uniqueness are involved, one relating to the model's equations and its
      parameters, the other to the number of available observations in time. The
      assessment of the first uniqueness condition involves rather tedious matrix
      algebra, requiring the appropriate mathematical expertise. We therefore give some
      general results for a particular class of PBPK models, indicating in what
      situations the first uniqueness condition either holds or does not. The
      assessment of the second uniqueness condition does not require specialized
      skills, and the minimum number of observations in time necessary can be easily
      determined for any particular situation. The practical implications for both
      modeling strategies and experimental protocols are discussed.

PMID- 9189656
TI  - Clinicoepidemiological, toxicological, and safety evaluation studies on argemone
      oil.
AB  - Consumption of oil extracted from accidental or deliberate contamination of
      argemone seed to mustard seed is known to pose a clinical condition popularly
      referred to as Epidemic Dropsy. Several outbreaks of Epidemic Dropsy have
      occurred in the past in India as well as in Mauritius, Fiji Island, and South
      Africa. Clinico-epidemiological manifestations of argemone oil poisoning include
      vomiting, diarrhea, nausea, swelling of limbs, erythema, pitting edema,
      breathlessness, etc. In extreme cases, glaucoma and even death due to cardiac
      arrest have been encountered. The toxicity of argemone oil has been attributed to
      two of its physiologically active benzophenanthridine alkaloids, sanguinarine and
      dihydrosanguinarine. Histopathological studies suggest that liver, lungs, kidney,
      and heart are the target sites for argemone oil intoxication. Studies have shown
      to elucidate the cocarcinogenic potential of argemone oil that can be correlated
      with the binding of sanguinarine with a DNA template. Pharmacological response in
      intestine revealed immediate stimulation of tone and peristaltic movements of the
      gut in the sanguinarine-treated animals. Argemone oil/Sanguinarine caused a
      decrease in hepatic glycogen levels which may be due to the activation of
      glycogenolysis leading to an accumulation of pyruvate in the blood of Epidemic
      Dropsy cases. The increase in pyruvate levels causes uncoupling of oxidative
      phosphorylation leading to breathlessness, as observed in patients. Sanguinarine
      has been shown to inhibit Na+, K(+)-ATPase activity of different organs such as
      brain, heart, liver, intestine, and skeletal muscle, which may be due to the
      interaction with the glycoside receptor site on ATPase enzyme, thereby causing a
      decrease in the active transport of glucose. Argemone oil/alkaloid showed a Type
      II binding spectra with hepatic cytochrome P-450 (P-450) protein, thereby causing
      loss of P-450 content and an impairment of phase I and phase II enzymes. A green
      fluorescent metabolite of sanguinarine, benzacridine was detected in the milk of
      grazing animals. The delayed appearance of this metabolite in urine and feces of
      experimental animals suggests the slow elimination of the alkaloid. Argemone oil
      enhances hepatic microsomal and mitochondrial lipid peroxidation, indicating that
      these two organelles are the sites of membrane damage. Furthermore, studies
      suggest that singlet oxygen and hydroxyl radical are involved in argemone oil
      toxicity. Several bioantioxidants show protective effect in argemone oil-induced
      toxicity in experimental animals. The line of treatment in argemone-intoxicated
      epidemics has so far been only symptomatic, and specific therapeutic measures are
      still lacking, although it has been suggested that diuretics, bioantioxidants,
      steroids, vitamins, calcium- and protein-rich diet had some beneficial effects on
      Epidemic Dropsy cases.

PMID- 9189658
TI  - Update on management of patients with Nocardia infection.

PMID- 9189657
TI  - The molecular biology of neuronal nicotinic acetylcholine receptors.
AB  - The molecular cloning of genes encoding neuronal nicotinic acetylcholine
      receptors (nAChRs) has made possible a better understanding of the pharmacology
      and toxicology of cholinergic compounds. Neuronal nAChRs are related in structure
      to the nAChRs present at the neuromuscular junction. They are composed of
      multiple subunits designated either alpha and beta. Eight alpha and three beta
      subunit genes have been cloned. The alpha subunits contain the ligand binding
      sites, whereas beta subunits are structural subunits that contribute to the
      function of the receptor. A large number of nAChRs can be formed from different
      combinations of alpha and beta subunits. Different combinations of alpha and beta
      subunits can produce receptors in vitro with distinct ion conducting properties.
      Each subunit gene is expressed in a distinct pattern in the nervous system. The
      expression of at least some of the nAChR subunit genes is regulated during
      development and by cell-cell interactions. Each neuronal nAChR subtype has a
      distinct pharmacology. Both alpha and beta subunits contribute to the
      pharmacological properties of each subtype. The expression of multiple nAChR
      subtypes may allow for precise control of neurotransmission mediated by
      acetylcholine in diverse populations of neurons.

PMID- 9189659
TI  - Pertussis in the 1990s: diagnosis, treatment, and prevention.

PMID- 9189660
TI  - Pyomyositis as a nontropical disease.

PMID- 9189661
TI  - Coagulase-negative staphylococcal infections: an update regarding recognition and
      management.

PMID- 9189662
TI  - Factitious fever: a modern update.

PMID- 9189663
TI  - Radionuclide imaging of infection in soft tissue and bone.

PMID- 9189664
TI  - The varicella vaccine.

PMID- 9189665
TI  - The uncommon gastrointestinal Protozoa: Microsporidia, Blastocystis, Isospora,
      Dientamoeba, and Balantidium.

PMID- 9189666
TI  - Coccidioidomycosis.

PMID- 9189667
TI  - New fungal pathogens.

PMID- 9189668
TI  - Daily dosage of aminoglycosides.

PMID- 9189670
TI  - Bartonella infections.

PMID- 9189669
TI  - Cyclospora.

PMID- 9189671
TI  - Alcohol and infection.

PMID- 9189672
TI  - Use of oral cephalosporins in infants and children.

PMID- 9189673
TI  - The long QT syndrome.

PMID- 9189674
TI  - Basic laser principles.
AB  - Skin diseases have been treated with lasers since the early 1960s. The three
      principal chromophores in the skin--hemoglobin, melanin, and water--have
      different absorption spectra that selectively absorb certain wavelengths of
      electromagnetic radiation. A given wavelength and pulse duration will selectively
      treat a target containing a chromophore. The wide variety of lasers and their
      applications are discussed.

PMID- 9189675
TI  - Laser treatment of port-wine stains and hemangiomas.
AB  - Since their discovery, lasers have truly advanced and broadened our options for
      the treatment of port-wine stains and hemangiomas. It is a blending of many
      sciences and much effort that allows us the opportunity today to selectively
      treat these vascular processes with relative effectiveness and significant
      safety. Ongoing study and development continue to offer hope on increasing
      benefit for our patients. Laser systems with variable wavelengths, pulse
      durations, and delivery methods will help accommodate the diversity of various
      port-wine stains and hemangiomas that are encountered in medicine.

PMID- 9189676
TI  - Laser treatment of acquired vascular lesions.
AB  - Several quasi-continuous wave and pulsed lasers can effectively treat a variety
      of vascular lesions. The PDL follows the theory of selective photothermolysis, is
      safe for infants and children, and has a low incidence of side effects. It is
      successful in treating telangiectasias, spider and cherry angiomas, pyogenic
      granulomas, venous lakes, and poikiloderma of Civatte, as well as small leg
      telangiectasias. Quasi-continuous wave lasers such as the APTDL, copper vapor,
      krypton, and KTP lasers can be used to treat telangiectasias and other vascular
      lesions as well. Although they carry a higher risk of complications, they may
      prove more useful in treating larger caliber vessels. Although the PDL often
      produces superior clinical results than the quasi-continuous wave lasers, some
      patients may prefer these latter lasers because of the lack of post-operative
      purpura. Lastly, newer lasers, as well as noncoherent light sources, are being
      developed for the treatment of leg telangiectasias. Continuing advances in laser
      technology will enhance results, decrease side effects, improve equipment, and
      reduce costs, with great benefit to an increasing patient population.

PMID- 9189677
TI  - Laser treatment of pigmented lesions.
AB  - Several pigment-specific lasers can effectively treat epidermal and dermal
      pigmented lesions without complications using the basic principles of selective
      photothermolysis. Although such pigmented lesions as solar lentigines and nevi of
      Ota are relatively easy to treat using pigment-specific laser technology, cafe-au
      lait macules and melasma show variable responses to treatment. New, long-pulsed
      pigment-specific lasers may prove to further enhance the clinical results
      obtained in resistant pigmented lesions and other conditions.

PMID- 9189678
TI  - Laser treatment of tattoos.
AB  - All three Q-switched laser systems can effectively remove most tattoos with
      minimal scarring or other adverse sequelae. Despite advances in laser technology,
      all tattoos cannot be completely eliminated, and several wavelengths remain
      necessary to optimally treat multicolored tattoos. The major advantage of Q
      switched laser irradiation to effect tattoo removal is the low risk of scarring
      associated with treatment. Limitations include the need for multiple treatment
      sessions, minimal to incomplete responses in some cases, and the possibility of
      pigmentary and textural changes. Research continues in an effort to perfect laser
      removal of tattoos.

PMID- 9189679
TI  - Laser treatment of hypertrophic scars, keloids, and striae.
AB  - Lasers are now being used successfully to improve various types of scars and
      striae. It is not only imperative to properly categorize the type of scars and
      striae present, but to determine which laser or lasers can best treat them. A 585
      nm flashlamp pumped pulsed dye laser is preferred for the treatment of
      hypertrophic scars, keloids, and striae distensae. CO2 laser vaporization of
      scars that are proliferative, such as hypertrophic scars and keloids, is not
      advised due to the high rate of recurrence or worsening. When properly used,
      lasers can effect the best clinical responses in hypertrophic scars and keloids
      ever observed. Future laser technologic advances as well as the addition of
      concomitant lasers or other treatments may enhance clinical results. It appears
      evident that by promoting the remodeling phase of wound healing, abnormal
      scarring may be prevented or improved. Laser surgery may best be able to
      accomplish this by triggering regression of blood vessels and, therefore,
      fibroblasts within the scar. By so doing, further deposition of connective tissue
      may be halted.

PMID- 9189680
TI  - Laser resurfacing of rhytides.
AB  - A discussion of the pathologic findings found with aging and photodamage is used
      to formulate a rational preoperative regimen, treatment technique, and
      maintenance regimen. Details of laser treatment technique, anesthesia, and
      postoperative care are given. Possible contraindications are discussed, as are
      the pros and cons of early versus late treatment.

PMID- 9189681
TI  - Laser resurfacing of atrophic scars.
AB  - Many patients seek treatment for the disfigurement caused by obvious variations
      in skin texture secondary to atrophic scarring. Many different procedures,
      including dermabrasion, chemical peels, punch grafting, and augmentation with
      filling materials, have been implemented for the treatment of atrophic scars.
      With the advent of high-energy, pulsed and scanned CO2 laser technology,
      precisely controlled, layer-by-layer tissue vaporization may be achieved with
      minimal thermal damage to adjacent skin. Atrophic scars resulting from acne,
      surgery, or trauma respond more favorably to laser resurfacing than to other,
      more conventional forms of treatment when proper techniques are employed.

PMID- 9189682
TI  - Histology of laser resurfacing.
AB  - The development of high-peak power or scanned CO2 lasers that precisely remove
      layers of photodamaged skin has provided a novel method of skin rejuvenation.
      Clinical data suggest that laser resurfacing provides comparable or better
      results than conventional methods of chemical peeling and mechanical
      dermabrasion, with a lower risk-to-benefit ratio. Histologic studies of the
      effects of these lasers on tissue have been helpful in establishing guidelines
      for appropriate clinical use of these lasers and insights into the mechanisms
      whereby facial skin rejuvenation is achieved.

PMID- 9189683
TI  - Laser-assisted hair removal.
AB  - The use of lasers in the treatment of a number of different skin disorders and
      diseases has become commonplace. This tremendous acceptance by both physicians
      and patients is a direct reflection of the high degree of precision and
      selectivity provided by lasers, which helps to minimize the risk of side effects
      and complications while simultaneously maximizing the opportunity for obtaining a
      satisfactory outcome. In an attempt to remove unwanted or excess hair, the
      principles of selective photothermolysis have been employed with several
      different laser and light devices that permit the effective treatment of large
      areas of hair-bearing skin with minimal discomfort and with low risk of scarring
      or other complications. It is possible using current laser technology to
      permanently remove some hair and induce a prolonged delay in the regrowth of many
      hairs. With additional experience and an improved understanding of how light can
      influence the rate and quality of hair growth, it is anticipated that permanent
      hair removal will be achieved in the near future.

PMID- 9189684
TI  - Laser hair transplantation.
AB  - A review of the present state of the art of laser hair transplantation highlights
      recommendations for treatment parameters and discusses the studies published in
      the literature. An evolving field, laser hair transplantation is maturing to find
      its place in the armentarium for hair restoration surgery.

PMID- 9189685
TI  - Laser treatment of warts and other epidermal and dermal lesions.
AB  - The CO2 laser is a versatile and effective tool for the treatment of warts and
      various other epidermal and dermal lesions where there is no easily targeted
      chromophore other than water. The development of high peak power, short-pulse, or
      rapidly scanned resurfacing CO2 lasers has significantly improved the safety and
      efficacy of using the CO2 laser. Many lesions amenable to CO2 laser vaporization
      can be treated by other far less expensive treatment modalities, however, and it
      is the laser surgeon's responsibility to use the CO2 laser only in cases in which
      it is demonstrably the best treatment option. The pulsed dye laser may replace
      the CO2 laser for the treatment of recalcitrant warts if the impressive early
      cure rates reported are borne out over time. Newer laser systems such as the
      Er:YAG laser with its extremely small zone of thermal damage may supplant the CO2
      laser in the treatment of other epidermal and dermal lesions in the future.

PMID- 9189686
TI  - Current status of photodynamic therapy in dermatology.
AB  - The accessibility of skin to light treatment, as well as the expertise developed
      by dermatologists in laser surgery and phototherapy, creates an exciting
      opportunity for dermatologic PDT to become part of our standard therapeutic
      armamentarium. PDT appears to be viable alternative to conventional therapy for
      superficial BCC and Bowen's disease, although definitive controlled studies are
      lacking. The introduction of ongoing research developments, new photosensitizers,
      and better light sources into clinical PDT trials in the coming years will
      undoubtedly expand the range of indications for this novel form of therapy,
      particularly for nononcologic conditions.

PMID- 9189687
TI  - Complications of laser surgery.
AB  - Medical lasers have advanced so rapidly over the past 10 years that a thorough
      review of the complications of laser surgery must be based on fundamental laser
      physics in order to provide a general working framework of knowledge. New laser
      systems are being introduced and older systems have been improved, often making
      modern laser technology appear intimidating. In order to understand and even
      predict the side-effect profile of a specific laser, one must comprehend the
      principles on which the laser operates. The first medical lasers to be designed,
      continuous wave lasers, are effective but are extremely operator-dependent and
      can potentially result in a great deal of scarring. In 1983, the theory of
      selective photothermolysis was introduced that enabled physician-scientists to
      design lasers that were highly selective and safer to operate. Lasers designed on
      the theory of selective photothermolysis are capable of affecting a specific
      target tissue without a high risk of scarring and pigmentary changes. They
      accomplish this task by producing a wavelength and pulse duration that are best
      absorbed by a specific target. Not all modern lasers use selective
      photothermolysis and therefore may operate in either a continuous wave, quasi
      continuous wave, pulsed, or Q quality-switched mode. Continuous wave lasers are
      least selective and tend to produce unwanted tissue damage and scarring through
      heat dissipation. Quasi-continuous wave lasers attempt to limit unwanted thermal
      damage by producing a series of brief laser pulses or by chopping a continuous
      wave beam; however, they still have a relatively high risk of causing nonspecific
      tissue damage and thermal injury. The pulsed and Q-switched systems adhere most
      closely to the laws of selective photothermolysis and result in the most
      selective destruction with the lowest risk of scarring and unwanted thermal
      diffusion. Of course, any laser system can potentially result in scarring and
      tissue damage; therefore, adequate operator education and skill are essential
      when using any medical laser.

PMID- 9189688
TI  - Oral antifungal drug interactions.
AB  - The recent approval of itraconazole and terbafine for the treatment of
      onychomycosis has launched a new era in the therapeutic management of this
      previously resistant form of dermatomycoses. These agents represent safe and
      effective treatments. The clinician should, however, become knowledgeable with
      the potential drug interactions that are discussed in this article.

PMID- 9189689
TI  - Anniversaries and attitudes.

PMID- 9189690
TI  - Bisphenol-A dental sealants: the inappropriateness of continued reference to a
      single female patient.

PMID- 9189691
TI  - Alpha 2 mu, alpha 2u, or alpha 2u.

PMID- 9189692
TI  - An ecological approach to public health intervention: Ross River virus in
      Australia.
AB  - A detailed look at the ecology of a disease can lead to recommendations for
      public health interventions that are not otherwise obvious. To illustrate this
      point, this paper discusses the ecology and control of infection with the
      Australian arbovirus Ross River virus (RRV). The traditional insecticidal
      approach to mosquito control is recommended when an outbreak of RRV results from
      the expansion of an area endemic for the disease to include a population of
      previously unexposed (nonimmune) people. In contrast, if an outbreak results from
      the expansion of a non-immune population into an endemic area, an insecticidal
      approach can lead to an increased incidence of the disease. Education about
      antimosquito measures is more appropriate in the latter situation; the differing
      applicability of these intervention strategies is highlighted. Both strategies
      could be more scientifically applied if endemic areas were clearly defined by
      modeling ecological variables and if intervention were more closely linked to
      improved surveillance systems. An ecologically based control strategy must be
      developed for RRV to manage the disease appropriately when faced with its
      probable ecological changes brought about by global warming, increased rainfall,
      and demographic change. Key words: arbovirus, ecology, endemic, epidemic, global
      change, intervention.

PMID- 9189693
TI  - New model for ozone transport.

PMID- 9189695
TI  - Children and the environment.

PMID- 9189694
TI  - Biocultural perspectives on women's health.

PMID- 9189696
TI  - New questions on genomic instability.

PMID- 9189697
TI  - Priorities for endocrine disruptor research.

PMID- 9189698
TI  - Environmental justice in action.

PMID- 9189699
TI  - The NIEHS recycles.

PMID- 9189701
TI  - Rating the legislative environment.

PMID- 9189700
TI  - A decent proposal? EPA's new clean air standards.

PMID- 9189702
TI  - Dissolving the plastics problem.

PMID- 9189703
TI  - Hepatocellular carcinoma p53 G > T transversions at codon 249: the fingerprint of
      aflatoxin exposure?
AB  - The molecular epidemiology of p53 mutations allows the possibility of correlating
      particular mutations with specific environmental carcinogens and establishing one
      step in the causal pathway between exposure to carcinogens and the development of
      cancer. A striking example is the G > T transversion at the third base pair of
      codon 249 observed in liver cancer patients possibly exposed to high levels of
      aflatoxins in their agricultural products. In this paper, we describe a
      systematic review of the literature and access the quality of the available data.
      We found methodologic limitations in the studies. In particular, the key
      independent variable, aflatoxin exposure, was not assessed in these studies, with
      the exception of one study that measured a marker of exposure. Instead,
      nationality, geographic residence, or geographic site of hospital were used as
      surrogate markers for exposure. Patients from areas with high aflatoxin levels
      were more likely to have p53 mutations than were patients from areas with low
      aflatoxin levels. In the group with p53 mutations, patients from areas with high
      aflatoxin levels had higher proportions of mutations with codon 249 G > T
      transversions. The differences in proportions with p53 mutations were
      significant, as were the differences in proportions of codon 249 G > T
      transversions among patients with p53 mutations. Aflatoxin may increase the
      proportion of p53 mutations by causing a single mutation, the codon 249 G > T
      transversion, thus explaining some of the excess liver cancer associated with
      aflatoxin exposure. However, it is premature to conclude that p53 mutations are
      established markers for environmental carcinogens.

PMID- 9189704
TI  - Lead exposure in Latin America and the Caribbean. Lead Research Group of the Pan
      American Health Organization.
AB  - As a result of the rapid industrialization of Latin America and the Caribbean
      during the second half of this century, exposure to lead has become an
      increasingly important problem. To obtain an estimate of the magnitude of lead
      exposure in the region, we carried out a survey and a literature search on
      potential sources of lead exposure and on blood lead concentrations. Sixteen out
      of 18 Latin American and 2 out of 10 Caribbean countries responded to the survey.
      Lead in gasoline remains a major problem, although the lead content has decreased
      in many countries in the last few years. The impact of leaded fuel is more
      important in urban settings, given their high vehicular density. Seventy-five
      percent of the population of the region lives in urban areas, and children
      younger than 15 years of age, the most susceptible group, comprise 30% of the
      population. Other sources of lead exposure identified in the region included
      industrial emissions, battery recycling, paint and varnishes, and contaminated
      food and water. Lead is recognized as a priority problem by national authorities
      in 72% of the countries that responded to the survey, and in 50% of the countries
      some legislation exists to regulate the lead content in certain products.
      However, compliance is low. There is an urgent need for a broad-based coalition
      between policy makers, industry, workers, unions, health care providers, and the
      community to take actions to reduce environmental and occupational lead exposures
      in all the Latin American and Caribbean countries.

PMID- 9189705
TI  - Biological monitoring of child lead exposure in the Czech Republic.
AB  - The area around the Pribram lead smelter has been recognized to be heavily
      contaminated by lead (Pb). In the early 1970s, several episodes of livestock lead
      intoxication were reported in this area; thereafter, several epidemiological and
      ecological studies focused on exposure of children. In contrast to earlier
      studies, the recent investigation (1992-1994) revealed significantly lower
      exposure to lead. From 1986-1990, recorded average blood lead levels were about
      37.2 micrograms lead (Pb)/100 ml in an elementary school population living in a
      neighborhood close to the smelter (within 3 km of the plant). The present study,
      however, has found mean blood lead levels of 11.35 micrograms/100 ml (95% CI =
      9.32; 13.82) among a comparable group of children. In addition to blood lead,
      tooth lead was used to assess exposure among children. Statistically significant
      differences (p < 0.05) were observed between the geometric mean tooth lead level
      of 6.44 micrograms Pb/g (n = 13; 95% CI = 3.95; 10.50) in the most contaminated
      zone and 1.43 micrograms Pb/g (n = 35; 95% CI = 1.11; 1.84) in zones farther away
      from the point source. Both biomarkers, blood and tooth lead levels, reflect a
      similar pattern of lead exposure in children. This study has attempted a
      quantitative assessment of risk factors associated with elevated lead exposure in
      the Czech Republic. Content of lead in soil, residential distance from the
      smelter, consumption of locally grown vegetables or fruits, drinking water from
      local wells, the mother's educational level, cigarette consumption among family
      members, and the number of children in the family were factors positively related
      (p < 0.05) to blood lead levels. The resulting blood lead level was found to be
      inversely proportional to the child's age.

PMID- 9189706
TI  - Lead exposure at an early age substantially increases lead retention in the rat.
AB  - It has been hypothesized that the high rate of bone remodeling during childhood
      and the consequent high calcium and lead turnover result in a substantial
      reduction in bone lead stores so that much of the lead incorporated in bone
      during childhood does not persist into adulthood. We studied the effect of age at
      lead exposure on blood and organ concentrations of lead, calcium, and zinc 1-5
      months after termination of lead ingestion. Blood and organ lead concentrations
      and contents 4 weeks after lead exposure ceased were significantly higher in the
      rats exposed beginning at 5 weeks of age than in those exposed beginning at 10 or
      15 weeks old. Bone lead declined as the time since exposure increased. Despite
      this trend, the rats exposed when youngest had bone lead concentrations at 20
      weeks after the termination of lead exposure that were higher than those of the
      other rats only 4 weeks after cessation of lead ingestion. Multiple regression
      analysis demonstrated that age at lead exposure remained a significant predictor
      of blood and organ lead concentrations and contents even after the inclusion of
      total lead consumed, body weight, and age at organ harvesting in the regression
      analysis. There were only small differences in organ calcium and zinc
      concentrations among treatment groups except for kidney calcium. The results do
      not support the hypothesis of rapid depletion of bone lead stores in young
      animals, but rather suggest that younger age at lead exposure is associated with
      greater lead retention and toxicity even in the absence of continued lead
      exposure.

PMID- 9189707
TI  - Fish zona radiata (eggshell) protein: a sensitive biomarker for environmental
      estrogens.
AB  - Environmental estrogens have recently caused great concern because of their
      ability to mimic natural hormones and influence vital endocrine functions in
      humans and wildlife. The induction of vitellogenin (Vtg) synthesis by
      environmental estrogens in viviparous vertebrates has been proposed as an
      effective and sensitive biomarker of estrogenicity. Immunochemical analysis of
      plasma from Atlantic salmon (Salmo salar) exposed to 4-nonylphenol (NP) or to
      effluent from oil refinery treatment plant (ORTP), shows that NP and ORTP
      effluent induces Vtg and zona radiata proteins (Zrp) in a dose-dependent manner.
      However, Zrp-beta cross-reactive proteins are more responsive than Zrp-alpha, Zrp
      gamma, and Vtg. The sensitivity of Zrp induction points to the zona radiata
      proteins as alternate biomarkers of estrogenicity.

PMID- 9189708
TI  - Biological monitoring for mercury within a community with soil and fish
      contamination.
AB  - To assess the impact of elevated levels of inorganic mercury in soil and dust and
      organic mercury in fish, biological monitoring was conducted among Native
      Americans living next to an inactive mercury mine in Clear Lake, California. Of
      resident tribal members, 46% (n = 56) participated in biomonitoring. Urine
      mercury levels are equivalent to background, indicating that soil and dust
      exposures among study participants are not substantial. The average blood organic
      mercury level among study participants is 15.6 +/- 8.8 micrograms/l (n = 44),
      which is higher than levels reported by others among those who do not consume
      fish (2 micrograms/l). Consistent with results from other studies, a correlation
      between fish consumption and blood organic mercury is observed (p = 0.03). The
      margin between observed and established adverse effect levels for adults is
      examined for blood organic mercury and found to be less than 10-fold for 20% of
      the study population. Protective public health efforts for the study population
      and other similarly exposed populations, notably those who consume commercial
      fish products, are considered.

PMID- 9189710
TI  - Stress proteins in reproductive toxicology.

PMID- 9189709
TI  - Medication use modifies the health effects of particulate sulfate air pollution
      in children with asthma.
AB  - Previous controlled studies have indicated that asthma medication modifies the
      adverse effects of sulfur dioxide (SO2) on lung function and asthma symptoms. The
      present report analyzed the role of medication use in a panel study of children
      with mild asthma. Children from Sokolov (n = 82) recorded daily peak expiratory
      flow (PEF) measurements, symptoms, and medication use in a diary. Linear and
      logistic regression analyses estimated the impact of concentrations of sulfate
      particles with diameters less than 2.5 microns, adjusting for linear trend, mean
      temperature, weekend (versus weekday), and prevalence of fever in the sample.
      Fifty-one children took no asthma medication, and only 31 were current medication
      users. Most children were treated with theophylline; only nine used sprays
      containing beta-agonist. For the nonmedicated children, weak associations between
      a 5-day mean of sulfates and respiratory symptoms were observed. Medicated
      children, in contrast, increased their beta-agonist use in direct association
      with an increase in 5-day mean of sulfates, but medication use did not prevent
      decreases in PEF and increases in the prevalence of cough attributable to
      particulate air pollution. Medication use was not a confounder but attenuated the
      associations between particulate air pollution and health outcomes.

PMID- 9189711
TI  - Bacterial DD-transpeptidases and penicillin.

PMID- 9189712
TI  - Sphingolipid activator proteins.

PMID- 9189713
TI  - Oxygen toxicity, free radicals and antioxidants in human disease: biochemical
      implications in atherosclerosis and the problems of premature neonates.

PMID- 9189714
TI  - Reconstructed human skin: transplant, graft or biological dressing?

PMID- 9189715
TI  - Opsin genes.

PMID- 9189716
TI  - The roles of molecular chaperones in vivo.
AB  - Table 1 summarizes the families of chaperones mentioned in this review, and lists
      their proposed functions. Many of these proteins are named in the accompanying
      review of Burston and Clarke. Molecular chaperones are proteins which interact
      with other proteins and help them to reach their final, active conformation. They
      appear to do this by binding them in an unfolded or partially folded state and
      subsequently releasing them in an altered form. This property may endow them with
      several essential or important roles in addition to helping newly synthesized
      proteins to fold correctly, such as repairing damaged proteins and assisting
      proteins in membrane translocation. To confirm that a given protein has molecular
      chaperone activity in vivo, it is necessary to show that interactions between the
      chaperone and other proteins do occur in the cell, and that loss of the molecular
      chaperone leads to the accumulation of inactive or precursor protein. The hsp70
      protein family are highly conserved and ubiquitous. Genetic studies confirm that
      their depletion leads to the accumulation of inactive precursor or other
      proteins, and immunochemical studies show they associate with nascent
      polypeptides. They are implicated not only in protein folding, but also in
      protein transport across membranes and reactivation of heat-damaged proteins. The
      hsp60 proteins are also ubiquitous and very similar in sequence. Those found in
      bacteria and organelles, such as mitochondria (the GroEL family), are essential
      at all temperatures, and particularly after heat shock. Their loss or depletion
      leads to the formation of protein aggregates and eventual cell death. A co
      chaperone protein (GroES) is required for their function. Cytosolic homologues
      (the TCP1 family) are also essential, though not heat-shock induced; they are
      believed to have a chaperone role in tubulin assembly and their actual role in
      the cell may be much broader. Many other proteins may have a chaperone function
      in vivo. Such a function may be specific to a particular substrate (such as the
      PapD protein in E. coli); others may be more general (such as hsp90 and SecB).
      Evidence is still needed to demonstrate whether all those proteins which show
      chaperone behaviour in vitro actually have such a role in vivo. It seems likely
      that different classes of chaperone may overlap in their specificity, and it is
      certain that the various proteins classed as molecular chaperones fulfil a wide
      variety of roles in the cell.

PMID- 9189717
TI  - Molecular chaperones: physical and mechanistic properties.
AB  - Molecular chaperones can be broadly defined as proteins which interact with non
      native states of other protein molecules. This activity is important in the
      folding of newly synthesized polypeptides and the assembly of multisubunit
      structures; the maintenance of proteins in unfolded states suitable for
      translocation across membranes; and the stabilization of inactive forms of
      proteins which are turned on by cellular signals; and the stabilization of
      proteins unfolded during cellular stress. The major chaperone classes are hsp60
      (including TCP1), hsp70 and hsp90. All these proteins prevent the aggregation of
      unfolded proteins and the strength of interaction with their protein substrates
      is modified by the binding and hydrolysis of ATP. Hsp70 is a dimeric and
      ubiquitous protein which binds its substrates in an extended conformation through
      hydrophobic interactions. It binds to newly synthesized proteins and is required
      for protein transport. In its ATP-bound state it has a low protein affinity but
      when the nucleotide is hydrolysed to give the ADP state the affinity is
      increased. Hsp70 in E. coli (DnaK) is regulated by two co-proteins: DnaJ (of
      which there are homologues in eukaryotes) stimulates hydrolysis of ATP and GrpE
      promotes the dissociation of ADP to allow rebinding of ATP. Thus DnaJ promotes
      the association of substrate proteins and GrpE promotes dissociation. Hsp60 is a
      large, tetradecameric protein with a central cavity in which non-native protein
      structures are proposed to bind. It is essential for the folding of a huge
      spectrum of unrelated proteins and is present in all biological compartments
      except the ER. As in hsp70, the binding of ATP stimulates release of the
      substrate and its hydrolysis restores high binding affinity. It functions in
      conjunction with a co-protein, cpn10, which enhances its ability to eject
      proteins during the ATPase cycle. The enhancement of folding yields arises either
      from the prevention of irreversible aggregation or the ability to unfold
      misfolded structures and allow further attempts to arrive at the native state.
      Proteins of the hsp90 class are found associated with inactive or unstable
      substrate proteins within the cell, thus preventing their aggregation and/or
      permitting rapid activation.

PMID- 9189718
TI  - Affinity precipitation: a novel approach to protein purification.

PMID- 9189719
TI  - Molecular pathology of prion diseases.

PMID- 9189720
TI  - Ribozymes.

PMID- 9189721
TI  - Protein stability at high temperatures.
AB  - The enzymology of hyperthermophilic micro-organisms is a growing field. As
      increasing numbers of novel high-temperature organisms are isolated and made
      available through culture collections, and, as biomass becomes more readily
      available, more laboratories will undoubtedly expand their research interests
      into this area. The prospect of totally novel enzyme systems and of new
      approaches to the investigation of fundamental molecular properties will continue
      to stimulate interest in this field. Studies of thermostable enzymes have already
      provided valuable data on the relationships between protein stability and
      activity. The subtle molecular mechanisms which have evolved to stabilize these
      proteins provide the clues needed for the intelligent design of stabilized
      mesophilic enzymes, an important target where a combination of high activity at
      'low' temperatures and resistance to denaturation is required. The current role
      of hyperthermophilic enzymes in biotechnology is relatively minor, despite these
      enzymes having a high 'profile'. While early over-enthusiastic predictions that
      these enzymes would revolutionize biotechnology should be disregarded, it can
      reasonably be assumed that, where functional and economic criteria are suitable,
      thermophilic enzymes will be readily incorporated into current and future
      biotechnology.

PMID- 9189722
TI  - Lymphocyte proliferation in response to exercise.
AB  - Lymphocyte proliferative responses are often used to evaluate the functional
      capacity of the immune system in response to exercise. Blood mononuclear cells
      (BMNC) are stimulated in vitro with polyclonal mitogens and the incorporation of
      3H-thymidine into the DNA reflects cell proliferation. The BMNC are most often
      stimulated with either phytohaemagglutinin (PHA), poke weed mitogen (PWM),
      concanavalin A (Con-A), interleukin-2 (IL-2), or purified derivative of
      tuberculin (PPD). The literature concerning lymphocyte proliferation and exercise
      is reviewed with respect to the type and intensity of exercise, and also the
      effect of training status. The proliferative responses to exercise are highly
      heterogeneous, the most consistent finding being that PHA-stimulated cell
      responses decrease during exercise which may reflect a decreased fraction of CD3+
      cells. In contrast, reduced, elevated or even unchanged lymphocyte proliferative
      response to PHA, PWM, Con-A, IL-2 and PPD have been demonstrated in the recovery
      period following exercise. Also variable responses are present in trained
      athletes compared to less fit subjects. Even though this may reflect that the
      time of 3H-thymidine incorporation into lymphocytes varies, we conclude that a
      functional evaluation of the immune system in response to exercise cannot be
      based solely upon measurements of lymphocyte proliferation.

PMID- 9189723
TI  - Quantitative assessment of degenerative changes in soleus muscle after hindlimb
      suspension and recovery.
AB  - The aim of this study was to quantify the degenerative and regenerative changes
      in rat soleus muscle resulting from 3-week hindlimb suspension at 45 degrees tilt
      (HS group, n = 8) and 4-week normal cage recovery (HS-R group, n = 7).
      Degenerative changes were quantified by microscope examination of muscle cross
      sections, and the myosin heavy chain (MHC) composition of soleus muscles was
      studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis. At the end
      of 3-week hindlimb suspension, histological signs of muscle degenerative changes
      were detected in soleus muscles. There was a significant variability in the
      percentage of fibres referred to as degenerating (%dg) in individual animals in
      the HS group [%dg = 8.41 (SEM 0.5)%, range 4.66%-14.08%]. Moreover, %dg varied
      significantly along the length of the soleus muscle. The percentage of fibres
      with internal nuclei was less than %dg in HS-soleus muscles [4.12 (SEM 0.3)%,
      range 1.24%-8.86%]. In 4-week recovery rats, the greater part of the fibres that
      were not referred to as normal, retained central nuclei [15.8 (SEM 2.2)%, range
      6.2%-21.1%]. A significant increase in the slow isoform of MHG was recorded in
      the HS-R rats, compared to muscles from age-matched rats (P < 0.01). These
      results would suggest that a cycle of myofibre degeneration-regeneration occurred
      during HS and passive recovery, and that the increased accumulation of slow MHC
      observed in soleus muscles after recovery from HS could be related to the
      prevalence of newly formed fibres.

PMID- 9189724
TI  - Blood flow in the carotid artery during breath-holding in relation to diving
      bradycardia.
AB  - The present study investigated the mechanism of diving bradycardia. A group of 14
      healthy untrained male subjects were examined during breath-holding either out of
      the water (30-33 degrees C), in heat-out immersion, or in whole-body submersion
      (27-29 degrees C) in a diving pool. Blood velocity, blood volume flow in the
      carotid artery, diastolic blood pressure and electrocardiogram were measured and
      recorded during the experiments. The peak blood velocity increased by 13.6% (P <
      0.01) and R-wave amplitude increased by 57.1% (P < 0.005) when the subjects
      entered water from air. End-diastolic blood velocity (Ved) in the carotid artery
      increased significantly during breath-holding, e.g. Ved increased from 0.20 (SD
      0.02) m.s-1 at rest to 0.33 (SD 0.04) m.s-1 (P < 0.001) at 50.0 s in breath-hold
      submersion to a 2.0-m depth. Blood volume flow in the carotid artery increased by
      26.6% (P < 0.05) at 30 s and 36.6% (P < 0.001) at 40 s in breath-hold submersion
      to a 2.0-m depth. Diastolic blood pressure increased by 15.4% (P < 0.01) at 60 s
      during breath-holding in head-out immersion. Blood volume flow, Ved and diastolic
      blood pressure increased significantly more and faster during breath-holding in
      submersion than out of the water. There was a good negative correlation with the
      heart rate: the root mean square correlation coefficient r was 0.73 (P < 0.001).
      It was concluded that an increased accumulation of blood in the aorta and
      arteries at end-diastole and decreased venous return, caused by an increase in
      systemic peripheral resistance during breath-holding, underlies diving
      bradycardia.

PMID- 9189725
TI  - The effect of endurance exercise at moderate altitude on serum lipid peroxidation
      and antioxidative functions in humans.
AB  - We investigated the effect of training and racing at moderate altitude (MA) on
      oxidative stress by assessment of serum diene conjugation (DC) and serum
      antioxidant potential (TRAP). Nine male top level skiers were studied during a
      national race (20-30 km) at sea level (SL). Thereafter, the athletes trained for
      2 weeks at MA, after which they participated in a 20-30 km race at MA. Venous
      blood samples were taken before and after the race. The DC, indicating early
      events of lipid peroxidation, did not change during the race at SL (16 850 vs 15
      900 delta Absorbance.l-1) or at MA (19 870 vs. 20 630 delta Abs.l-1). At MA serum
      DC was higher than at SL both before (25%) and after (30%) the race, the postrace
      difference being statistically significant (P < 0.05). The TRAP increased during
      the race at MA (from 1387 to 1943 mumol.l-1, P = 0.016), but not at SL (1713 vs
      1582 mumol.l-1). These observations would suggest that the level of oxidative
      stress might be greater during living, training and racing at MA (higher DC
      levels). Increased TRAP during the race at MA may indicate that the physiological
      adaptation to extreme acute oxidative stress was altered. The physiological
      significance of this observation remains to be investigated.

PMID- 9189726
TI  - Body fluid homeostasis and cardiovascular adjustments during submaximal exercise:
      influence of chewing coca leaves.
AB  - The present study was undertaken to determine the haematological and
      cardiovascular status, at rest and during prolonged (1h) submaximal exercise
      (approximately 70% of peak oxygen uptake) in a group (n = 12) of chronic coca
      users after chewing approximately 50 g of coca leaves. The results were compared
      to those obtained in a group (n = 12) of nonchewers. At rest, coca chewing was
      accompanied by a significant increase in heart rate [from 60 (SEM 4) TO 76 (SEM
      3) beats.min-1], in haematocrit [from 53.2 (SEM 1.2) to 55.6 (SEM 1.1)%] in
      haemoglobin concentration, and plasma noradrenaline concentration [from 2.8 (SEM
      0.4) to 5.0 (SEM 0.5) mumol.l-1]. It was calculated that coca chewing for 1 h
      resulted in a significant decrease in blood [-4.3 (SEM 2.2)%] and plasma [-8.7
      (SEM 1.2)%] volume. During submaximal exercise, coca chewers displayed a
      significantly higher heart rate and mean arterial blood pressure. The exercise
      induced haemoconcentration was blunted in coca chewers compared to nonchewers. It
      was concluded that the coca-induced fluid shift observed at rest in these coca
      chewers was not cumulative with that of exercise, and that the hypovolaemia
      induced by coca chewing at rest compromised circulatory adjustments during
      exercise.

PMID- 9189727
TI  - Effects of 3 days of carbohydrate supplementation on muscle glycogen content and
      utilisation during a 1-h cycling performance.
AB  - This study compared the effects of supplementing the normal diets of six trained
      cyclists [maximal oxygen uptake (VO2max) 4.5 (0.36) l.min-1; values are mean
      (SD)] with additional carbohydrate (CHO) on muscle glycogen utilisation during a
      1-h cycle time-trial (TT). Using a randomised crossover design, subjects consumed
      either their normal diet (NORM) for 3 days, which consisted of 426 (137) g.day-1
      CHO [5.9 (1.4) g. kg-1 body mass (BM)], or additional CHO (SUPP) to increase
      their intake to 661 (76) g.day-1 [9.3 (0.7) g. kg-1 BM]. The SUPP diet elevated
      muscle glycogen content from 459 (83) to 565 (62) mmol.kg-1 dry weight (d.w.) (P
      < 0.05). However, despite the increased pre-exercise muscle glycogen stores,
      there was no difference in the distance cycled during the TT [40.41 (1.44) vs
      40.18 (1.76) km for NORM and SUPP, respectively]. With NORM, muscle glycogen
      declined from 459 (83) to 175 (64) mmol.kg-1 d.w., whereas with SUPP the
      corresponding values were 565 (62) and 292 (113) mmol.kg-1 d.w. Accordingly, both
      muscle glycogen utilisation [277 (64) vs 273 (114) mmol.kg-1 d.w.] and total CHO
      oxidation [169 (20) vs 165 (30) g.h-1 for NORM and SUPP, respectively] were
      similar. Neither were there any differences in plasma glucose or lactate
      concentrations during the two experimental trials. Plasma glucose concentration
      averaged 5.5 (0.5) and 5.6 (0.6) mmol.l-1, while plasma lactate concentration
      averaged 4.4 (1.9) and 4.4 (2.3) mmol.l-1 for NORM and SUPP, respectively. The
      results of this study show that when well-trained subjects increase the CHO
      content of their diet for 3 days from 6 to 9 g.kg-1 BM there is only a modest
      increase in muscle glycogen content. Since supplementary CHO did not improve TT
      performance, we conclude that additional CHO provides no benefit to performance
      for athletes who compete in intense, continuous events lasting 1 h. Furthermore,
      the substantial muscle CHO reserves observed at the termination of exercise
      indicate that whole-muscle glycogen depletion does not determine fatigue at this
      exercise intensity and duration.

PMID- 9189728
TI  - Effect of ubiquinone on exercise-induced lipid peroxidation in rat tissues.
AB  - Changes in the amount of thiobarbituric acid-reactive substances (TBARS), an
      index of the lipid peroxidation, were estimated in liver, heart, and the red and
      white components of gastrocnemius muscle of control (C) and ubiquinone-treated
      rats (T, 10 mg.kg-1 daily, for 4 weeks) at rest, and 3 and 24 h after running
      until the rats were exhausted. The activity of creatine kinase in serum and the
      level of the non-protein sulphhydryl groups (NP-SH) in the above organs were also
      determined. The running time until exhaustion was longer in T than in C [83.0 (SD
      13.8) vs 72.2 (SD 14.8) min, P < 0.05]. The exercise resulted in a significant
      increase (P < 0.01) in the TBARS amounts in all the tissues obtained from C and
      in the liver and heart of T. The postexercise amounts of TBARS were significantly
      higher (P < 0.01) in C than in T. The resting amounts of NP-SH in the heart and
      liver were significantly higher (P < 0.05) in C compared to T. The exercise led
      to a decrease in the NP-SH content in the heart and liver (P < 0.05) of C but did
      not seem to affect the NP-SH contents in these tissues in T. No effect of
      ubiquinone treatment on postexercise increase in the serum creatine kinase
      concentration was found. It was concluded that in rats ubiquinone treatment
      markedly suppresses exercise-induced lipid peroxidation in such organs as liver,
      heart and gastrocnemius muscle.

PMID- 9189730
TI  - Exercise-induced oxyhemoglobin desaturation and pulmonary diffusing capacity
      during high-intensity exercise.
AB  - The purpose of this investigation was to examine if exercise-induced arterial
      oxyhemoglobin desaturation selectively observed in highly trained endurance
      athletes could be related to differences in the pulmonary diffusing capacity (DL)
      measured during exercise. The DL of 24 male endurance athletes was measured using
      a 3-s breath-hold carbon monoxide procedure (to give DLCO) at rest as well as
      during cycling at 60% and 90% of these previously determined VO2max.
      Oxyhemoglobin saturation (SaO2%) was monitored throughout both exercise protocols
      using an Ohmeda Biox II oximeter. Exercise-induced oxyhemoglobin desaturation
      (DS) (SaO2% < 91% at VO2max) was observed in 13 subjects [88.2 (0.6)%] but not in
      the other 11 nondesaturation subjects [NDS: 92.9 (0.4)%] (P < or = 0.05),
      although VO2max was not significantly different between the groups [DS: 4.34
      (0.65) l/min vs NDS: 4.1 (0.49) l/min]. At rest, no differences in either DLCO
      [ml CO.mmHg-1.min-1: 41.7 (1.7) (DS) vs 41.1 (1.8) (NDS)], DLCO/VA [8.2 (0.4)
      (DS) vs 7.3 (0.9) (NDS)], MVV [l/min: 196.0 (10.4) (DS) vs 182.0 (9.9) (NDS)] or
      FEV1/FVC [86.3 (2.2) (DS) vs 82.9 (4.7) (NDS)] were found between groups (P > or
      = 0.05). However, VE/VO2 at VO2max was lower in the DS group [33.0 (1.1)]
      compared to the NDS group [36.8 (1.5)] (P < or = 0.05). Exercise DLCO (ml CO.mmHg
      1.min-1) was not different between groups at either 60% VO2max [DS: 55.1 (1.4) vs
      NDS: 57.2 (2.1)] or at 90% VO2max [DS: 61.0 (1.8) vs NDS: 61.4 (2.9)]. A
      significant relationship (r = 0.698) was calculated to occur between SaO2% and
      VE/VO2 during maximal exercise. The present findings indicate that the exercise
      induced oxyhemoglobin desaturation seen during submaximal and near-maximal
      exercise is not related to differences in DL, although during maximal exercise
      SaO2 may be limited by a relatively lower exercise ventilation.

PMID- 9189729
TI  - Early metabolic adaptations of rabbit fast-twitch muscle to chronic low-frequency
      stimulation.
AB  - To investigate early adaptive responses to chronic low-frequency stimulation
      (CLFS), rabbit tibialis anterior (TA) muscles were continuously stimulated at 10
      Hz for 8 days, allowed to rest for 1 h, and then subjected to a 15-min fatigue
      test at 10-Hz stimulation. The contralateral TA muscles which had not been
      exposed to CLFS, served as controls during the fatigue test. Compared to the
      controls, the initial tension output of the 8-day prestimulated muscles was
      reduced by 25%. However, these muscles maintained higher tensions during the
      fatigue test than the controls. Citrate synthase activity, an indicator of
      aerobic-oxidative capacity, was only slightly elevated (40%) in the 8-day
      stimulated muscles. Unlike the controls, the prestimulated muscles failed to
      produce potentiation during the fatigue test. Control muscles responded to the
      fatigue test with pronounced reductions in contents of adenosine 5'-triphosphate
      (ATP), phosphocreatine (PCr), and glycogen, as well as with large increases in
      contents of inosine monophosphate (IMP), inorganic phosphate (Pi), creatine (Cr),
      and lactate. Under the same conditions contents of ATP, PCr, Cr, glycogen,
      lactate, Pi, and IMP were unaltered in the 8-day prestimulated muscles. These
      findings demonstrated that CLFS for 8 days elicited pronounced alterations in
      energy metabolism and contractile properties. These adaptive changes occurred
      prior to fibre type transitions and substantial increases in aerobic-oxidative
      potential.

PMID- 9189731
TI  - An evaluation of exercise cardiac output using the CO2 rebreathing extrapolation
      technique.
AB  - We investigated the reproducibility of the carbon dioxide (CO2) rebreathing
      extrapolation technique of Defares to determine the mixed venous partial pressure
      of CO2 (PvCO2) using a direct, rather than the commonly used indirect,
      extrapolation method. The PvCO2 determinations were made five times a day on four
      subjects who exercised for 4 h daily on a bicycle ergometer over a period of 13
      days. The concentration of CO2 in the rebreathing bag was monitored continuously
      using a rapid-response infrared capnograph. The mean standard deviation was 1.56
      mmHg (0.21 kPa) for a mean PvCO2 of 47.6 mmHg (6.3 kPa), giving a mean
      coefficient of variation of 3.3%. This level of reproducibility agrees favourably
      with the reliability of direct measurements of pulmonary arterial partial
      pressure of CO2. We conclude that the CO2 rebreathing extrapolation technique can
      give reproducible PvCO2 values when a direct method of extrapolation is used.

PMID- 9189732
TI  - Haemodynamic response to exercise in healthy young and elderly subjects.
AB  - Whereas with advancing age, peak heart rate (HR) and cardiac index (CI) are
      clearly reduced, peak stroke index (SI) may decrease, remain constant or even
      increase. The aim of this study was to describe the patterns of HR, SI, CI,
      arteriovenous difference in oxygen concentration (Ca-vO2), mean arterial pressure
      (MAP), systemic vascular resistance index (SVRI), stroke work index (SWI) and
      mean systolic ejection rate index (MSERI) in two age groups (A: 20-30 years, n =
      20; B: 50-60 years n = 20). After determination of pulmonary function, an
      incremental bicycle exercise test was performed, with standard, gas-exchange
      measurements and SI assessment using electrical impedance cardiography. The
      following age-related changes were found: similar submaximal HR response to
      exercise in both groups and a higher peak HR in A than in B[185 (SD 9) vs 167 (SD
      14) beats.min-1, P < 0.0005]; increase in SI with exercise up to 60-90 W and
      subsequent stabilization in both groups. As SI decreased towards the end of
      exercise in B, a higher peak SI was found in A [57.5 (SD 14.0) vs 43.6 (SD 7.7)
      ml.m-2, P < 0.0005]; similar submaximal CI response-to exercise, higher peak CI
      in A [10.6 (SD 2.5) vs 7.2 (SD 1.3) 1.min-1.m-2, P < 0.0005]; no differences in
      Ca-vO2 during exercise; higher MAP at all levels of exercise in B; higher SVRI at
      all levels of exercise in B; lower SWI in B after recovery; higher MSERI at all
      levels of exercise in A. The decrease in SI with advancing age would seem to be
      related to a decrease in myocardial contractility, which can no longer be
      compensated for by an increase in preload (as during submaximal exercise).
      Increases in systemic blood pressure may also compromise ventricular function but
      would seem to be of minor importance.

PMID- 9189733
TI  - Specificity of resistance training responses in neck muscle size and strength.
AB  - This study examined hypertrophy after head extension resistance training to
      assess which muscles of the complicated cervical neuromuscular system were used
      in this activity. We also determined if conventional resistance exercises, which
      are likely to evoke isometric action of the neck, induce generalized hypertrophy
      of the cervical muscle. Twenty-two active college students were studied. [mean
      (SE) age, weight and height: 21 (1) years, 71 (4) kg and 173 (3) cm,
      respectively]. Subjects were assigned to one of three groups: RESX (head
      extension exercise and other resistance exercises), RES (resistance exercises
      without specific neck exercise), or CON (no training). Groups RESX (n = 8) and
      RES (n = 6) trained 3 days/week for 12 weeks with large-muscle mass exercises
      (squat, deadlift, push press, bent row and mid-thigh pull). Group RESX also
      performed three sets of ten repetitions of a head extension exercise 3 days/week
      with a load equal to the 3 x 10 repetition maximum (RM). Group CON (n = 8) was a
      control group. The cross-sectional area (CSA) of nine individual muscles or
      muscle groups was determined by magnetic resonance imaging (MRI) of the cervical
      region. The CSA data were averaged over four contiguous transaxial slices in
      which all muscles of interest were visible. The 3 x 10 RM for the head extension
      exercise increased for RESX after training [from 17.9 (1.0) to 23.9 (1.4) kg, P <
      0.05] but not for RES [from 17.6 (1.4) to 17.7 (1.9) kg] or CON [from 10.1 (2.2)
      to 10.3 (2.1) kg]. RESX showed an increase in total neck muscle CSA after
      training [from 19.5 (3.0) to 22.0 (3.6) cm2, P < 0.05], but RES and CON did not
      [from 19.6 (2.9) to 19.7 (2.9) cm2 and 17.0 (2.5) to 17.0 (2.4) cm2,
      respectively]. This hypertrophy for RESX was due mainly to increases in CSA of
      23.9 (3.2), 24.0 (5.8), and 24.9 (5.3)% for the splenius capitis, and
      semispinalis capitis and cervicis muscles, respectively. The lack of generalized
      neck muscle hypertrophy in RES was not due to insufficient training. For example,
      the CSA of their quadriceps femoris muscle group, as assessed by MRI, increased
      by 7 (1)% after this short-term training (P < 0.05). The results suggest that:
      (1) the splenius capitis, and semispinalis capitis and cervicis muscles are
      mainly responsible for head extension; (2) short-term resistance training does
      not provide a sufficient stimulus to evoke neck muscle hypertrophy unless
      specific neck exercises are performed; and (3) the postural role of head
      extensors provides modest loading in bipeds.

PMID- 9189734
TI  - Unchanged response to stimulation of pituitary hormone release after serial UV
      irradiation in men.
AB  - A group of 24 healthy young men were evaluated before and after serial
      suberythematous ultraviolet (UV) radiation: group I, control (no irradiation);
      groups II and III, 12 radiations in 4 weeks with two different spectra (both
      containing UV-B). Before the first and 2 days after the last exposure all the
      volunteers were given an intravenous injection of thyrotropin releasing hormone
      (TRH, protirelin 0.2 mg) and luteinizing hormone releasing hormone (LH-RH,
      gonadorelin 0.1 mg). The serum concentrations of TSH, follicle stimulating
      hormone, LH and prolactin were measured at 0, 20, 30, 45 and 60 min by
      radioimmunoassay. Neither basal nor stimulated levels of the pituitary hormones
      showed significant changes after UV radiation. The results showed that exposure
      to suberythematous doses of UV did not influence the regulation of pituitary
      hormones in these healthy individuals.

PMID- 9189735
TI  - The development of an isokinetic squat device: reliability and relationship to
      functional performance.
AB  - This study was performed to determine the reliability and validity of a new
      isokinetic squat device in comparison to knee-extension tests performed using a
      Cybex. Athletic male subjects (n = 29) performed a series of isokinetic squat
      tests at 0.4 m.s-1, knee-extension tests at 1.05, 2.09 and 3.14 rad.s-1, and a 6
      s stationary cycle test which was used as the measure of functional performance.
      The squat tests included a purely concentric squat without pre-load, a test with
      pre-load and a stretch-shorten cycle test. Two trials of each test were performed
      on one testing occasion. Intraclass correlation co-efficients (r = 0.89-0.96) and
      co-efficients of variation (3.1-8.7%) were determined between trials, and these
      indicated that all of the tests were highly reliable. The velocity
      characteristics of the newly developed system demonstrated that it was an
      effective isokinetic device, with the mean velocity of 0.41 m.s-1 varying within
      narrow limits, a relatively small velocity overshoot and an isokinetic portion of
      movement of approximately 80%. The squat tests demonstrated a higher relationship
      to cycling performance (r = 0.57-0.65) as compared to the knee-extension tests (r
      = 0.45-0.51). This difference was amplified when a more homogeneous group of
      subjects was examined. Further, the squat tests were superior to the knee
      extension tests in discriminating between differing levels of cycling performance
      ability. These differences were believed to be due to the greater specificity of
      the squat movement, in comparison to the knee extension, to the performance of
      interest.

PMID- 9189736
TI  - The relationship between plasma potassium concentration and muscle torque during
      recovery following intense exercise.
AB  - The present study investigated the relationship between plasma potassium ion
      concentration ([K+]) and skeletal muscle torque during three different 15-min
      recovery periods after fatigue induced by four 30-s sprints. Four males and one
      female completed the multiple sprint exercise on three separate days; recovery
      was passive, i.e. no cycling exercise (PRec), active cycling at 30% peak oxygen
      consumption. VO2peak (30% Rec) and active cycling at 60% VO2peak (60% Rec).
      Plasma [K+] was measured from blood sampled from an antecubital vein of subjects
      at rest and at 0, 3, 5, 10 and 15 min into each recovery. Isokinetic leg strength
      was measured at rest and at 1, 6, 11 and 16 min during each recovery. Following
      the exhaustive sprints, [K+] increased significantly from an average mean (SEM)
      resting value of 3.81 (0.07) mmol.l-1 to 4.48 (0.19) mmol.l-1 (P < 0.01). In all
      recovery conditions, plasma [K+] returned to resting levels within 3 min
      following the fourth sprint. However, in the two active recovery conditions
      plasma [K+] increased over the remainder of the recovery periods to 4.36 (0.12)
      mmol.l-1 in the 30% Rec condition and 4.62 (0.12) mmol.l-1 in the 60% Rec
      condition, the latter being significantly higher than the former (P < 0.01). The
      maximum torque measured following the sprints decreased significantly, on
      average, to 61.1 (8.36)% of peak levels (P < 0.01). After 15 min of recovery,
      maximum torque was highest in the 30% Rec condition at 92.13 (3.06)% of peak
      levels (P < 0.01), compared to 85.23 (3.64)% and 85.71 (0.82)% for the PRec and
      60% Rec conditions, respectively. In contrast to the significant differences in
      plasma [K+] across all three recovery conditions, muscle torque recovery was
      significantly different in only the 30% Rec condition. In summary, recovery of
      peak levels of muscle torque following fatiguing exercise does not appear to
      follow changes in plasma [K+].

PMID- 9189737
TI  - Habitual long-distance running does not enhance urinary excretion of 8
      hydroxydeoxyguanosine.
AB  - The energy demand during physical exercise causes an increased oxygen uptake and
      supply to active tissues, which may increase the rate of free oxygen radical
      production and thereby affect the capacity of endogenous cellular defense
      systems. This could result in DNA base modifications, among which 8
      hydroxydeoxyguanosine (8OHdG) is one of the most important and has widely been
      used as a biomarker of in vivo oxidative lesions. Therefore, we examined the
      effect of regular running exercise on the urinary levels of 8OHdG in 32 long
      distance runners and in a group of untrained healthy subjects. The range of 8OHdG
      in urine was 0.12-6.45 mumol/mol creatinine in both groups, and no significant
      difference in the mean excretion levels between runners and control probands was
      observed. This gives no reason to believe that physical exercise in trained
      individuals may induce a disturbance of the oxidant-to-antioxidant balance.

PMID- 9189738
TI  - Eosinophil protein X concentration is dependent on eosinophil concentration.
AB  - The relationship between the eosinophil concentration and the serum eosinophil
      protein X concentration was investigated in 80 subjects. Higher eosinophil counts
      resulted in obviously increased serum eosinophil protein X concentrations.
      However, the amount of eosinophil protein X released per eosinophil granulocyte
      is significantly higher in subjects with lower eosinophil counts. Atopic subjects
      (N = 19) show a significantly higher eosinophil concentration (p = 0.002) and
      eosinophil protein X concentration (p = 0.004) and a significantly lower
      eosinophil protein X/eosinophil ratio (p = 0.02), compared with non-atopic
      subjects (N = 61). However, there appears to be no difference between the
      concentration of eosinophil protein X in atopic and non-atopic subjects if the
      eosinophil concentration is taken into account. When using eosinophil protein X
      as an indicator of eosinophil activation, for instance in asthmatic subjects, the
      eosinophil count should also be considered for correct clinical interpretation of
      results.

PMID- 9189740
TI  - Anti-insulin antibodies in insulin immunometric assays: a still possible pitfall.
AB  - Insulin was assayed directly using radioimmunoassay and immunometric assay in 31
      sera containing anti-insulin antibodies. Anti-insulin antibodies were determined
      by radio-binding-assay. Insulin measurements were compared with those of free
      (unbound to antibodies, polyethylene glycol precipitated) insulin measurements.
      Compared with free insulin concentrations, radioimmunoassay and immunometric
      assay yielded falsely increased insulin results. The degree of overestimation by
      radioimmunoassay and by immunometric assay correlated with the anti-insulin
      antibody value. Anti-insulin antibodies still remain a possible pitfall in the
      insulin-specific immunometric assays which are now being widely used.

PMID- 9189739
TI  - Elimination of tritium-labelled hyaluronic acid from normal and osteoarthritic
      rabbit knee joints.
AB  - The half-life of [3H]hyaluronic acid in rabbit knee joints was estimated using
      two methods: (i) by following the [3H]hyaluronan content of the synovial fluid
      after intra-articular injection and (ii) by following the 3H2O radioactivity of
      plasma after intra-articular injection of [3H]hyaluronan. For normal rabbits we
      obtained a half-life of 15.8 hours (method I) and 17.5 +/- 1.0 hours (mean +/-
      SEM, method II), respectively. The second method was used to estimate the
      kinetics of the hyaluronan elimination from normal, sham-operated, as well as
      from osteoarthritic rabbit knee joints (Colombo model of osteoarthritis). Four
      weeks after injury, during the developing phase of osteoarthritis, the half-life
      of hyaluronan rose significantly to 23.5 +/- 2.1 hours and returned to normal
      levels (17.4 +/- 2.7 hours) 12 weeks after the operation (osteoarthritis
      developed). At the stage of developed osteoarthritis, the clearance rates were
      considerably higher than in normal rabbits.

PMID- 9189741
TI  - Buflomedil interference with the monoclonal EMIT d.a.u.
      amphetamine/methamphetamine immunoassay.
AB  - The interference of buflomedil with the monoclonal and polyclonal EMIT d.a.u.
      amphetamine immunoassays was investigated. Urine samples collected from 20
      patients taking 600 mg of buflomedil daily gave false positive results with the
      monoclonal EMIT d.a.u. assay, as did urine specimens collected 2 hours after the
      first oral dose of buflomedil. Conversely, no false positive results occurred
      with the polyclonal EMIT d.a.u. amphetamine assay. Urine samples with buflomedil
      added at concentrations greater than 100 mg/l gave false positive results with
      the monoclonal immunoassay. Buflomedil concentrations found in the patient urines
      (56-400 mg/l) failed to correlate to EMIT assay responses: this result suggests
      that one or more buflomedil metabolites, besides the unchanged drug, probably
      interfere in the monoclonal EMIT d.a.u. assay.

PMID- 9189742
TI  - Two high performance liquid chromatographic methods for the determination of
      alpha-tocopherol in serum compared to isotope dilution-gas chromatography-mass
      spectrometry.
AB  - Two high performance liquid chromatographic methods (HPLC) with isocratic
      reversed-phase separation are presented for the determination of alpha-tocopherol
      (vitamin E) in serum. In the first method alpha-tocopherol acetate is used as
      internal standard, detection of absorbance is performed at 284 nm. In the second
      method tocol is used as internal standard, detection of fluorescence is performed
      with an excitation wavelength of 292 nm and emission wavelength of 325 nm. Both
      methods require a liquid-liquid extraction as sample preparation. The results of
      both HPLC methods have been tested by method comparison for n = 25 serum samples
      versus an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) method
      using alpha-tocopherol-d6 as internal standard. The imprecision within-run was
      lower than 2.5% for the UV method and lower than 1% for the fluorescence method
      for both standards and serum pools. The between-run imprecision, obtained for
      serum pools, was below 5% for the UV method and not higher than 1.5% for the
      fluorescence method and not higher 1.8% for the ID-GC-MS. Recovery experiments
      performed by spiking pool sera with alpha-tocopherol showed recoveries between
      98.5% and 100.6% for all methods studied. The result of the method comparison was
      a coefficient of correlation of r = 0.998 for the HPLC method with fluorescence
      detection to the ID-GC-MS reference method and a coefficient of correlation of r
      = 0.981 for the HPLC method with UV detection to the ID-GC-MS reference method.
      Both methods presented are useful for the analysis of alpha-tocopherol in patient
      samples. If detection of fluorescence is used, imprecision and inaccuracy of the
      HPLC method are comparable to the ID-GC-MS chosen as reference method.

PMID- 9189743
TI  - Insulin-like growth factor-I and its binding protein-3 in serum: are they good
      screening properties for the diagnosis of growth hormone deficiency?
AB  - Serum insulin-like growth factor-I and insulin-like growth factor binding protein
      3 are simply-determined screening analytes if growth hormone deficiency is
      suspected. The analysis of growth hormone secretion using standardised
      stimulation tests and secretion profiles is complicated and expensive in
      comparison. In retrospect, we have examined the value of insulin-like growth
      factor-I and its binding protein-3 for the diagnostic clarification of patients
      with short stature (n = 117). In 39/117 patients growth hormone secretion was
      investigated as ward patients. Growth hormone deficiency was diagnosed in 10
      patients, for 16 patients the diagnosis was neurosecretory dysfunction. For all
      patients (n = 7) with lowered insulin-like growth factor binding protein-3 and
      insulin-like growth factor-I values (insulin-like growth factor binding protein-3
      < 5th percentile, insulin-like growth factor-I < 10th percentile) a growth
      hormone disorder was proven. Conversely, however, only 3/10 patients with
      classical growth hormone deficiency (n = 3) showed a lowering of both analytes.
      8/10 patients with classical growth hormone deficiency and 8/16 patients with
      neurosecretory dysfunction had at least one lowered value. Two patients showed
      normal values for insulin-like growth factor-I and insulin-like growth factor
      binding protein-3 despite biochemically proven growth hormone deficiency. The
      combined determination of insulin-like growth factor-I and insulin-like growth
      factor binding protein-3 can provide valuable help during preliminary diagnosis
      of patients of short stature, indicating a disturbance of the growth hormone
      secretion if the values are lowered. Normal values do not, however, exclude the
      possibility of a growth hormone deficiency. Inpatient endocrinological testing is
      indispensible if growth hormone deficiency is suspected.

PMID- 9189744
TI  - Intermethod variability of sodium and potassium results: patients' sera and
      commercially available control sera.
AB  - Sodium and potassium were measured in sets of 102 to 107 patients sera, and in 31
      commercially available control sera. The results from four routine analytical
      methods/systems (indirect potentiometry: two; direct potentiometry and enzymatic
      assay: one each) were compared with those from a flame photometry-based reference
      method. In the assay of patient sera, substantial agreement was observed in some
      comparisons, clinically relevant bias in others. The inter-assay changes observed
      for the control sera differed significantly from those shown by the patients sera
      (i.e. commercial control sera were non-commutable) in about 12% of the
      comparisons, as a whole. Recalculation of serum sample results with a single
      control serum as calibrator lowered or increased the bias originally present
      according to whether the serum itself was commutable or not. Moreover, the inter
      method variability in the assay of commercial control sera was lower with
      commutable sera, higher with non-commutable sera. With the exception of liquid
      sera stabilized with ethylene glycol, there was no evident link between any
      specific characteristic of the commercial control sera (matrix and physical
      state) and their degree of commutability.

PMID- 9189745
TI  - Routine serum protein analysis using capillary electrophoresis.

PMID- 9189746
TI  - The ratio of non-oxidized/oxidized forms of apolipoprotein A-I can affect
      cholesterol efflux from human skin fibroblasts mediated by high density
      lipoprotein.

PMID- 9189747
TI  - Is 570 nm the wavelength of choice for scanning protein agarose electrophoresis
      plates stained with amidoschwarz?

PMID- 9189749
TI  - Award of the Felix Hoppe-Seyler prize of the German Society for Laboratory
      Medicine, of the Gabor Szasz Prize of the German Society for Clinical Chemistry
      and of the National IFCC-AVL Award.

PMID- 9189748
TI  - Evaluation of a rapid, quantitative cardiac troponin I immunoassay.
AB  - We evaluated a rapid, quantitative immunoassay for the detection of cardiac
      troponin I. Coefficient of variation is between 1.29 and 13.63% for intra-assay
      and between 3.88 and 10.15% for inter-assay imprecision. Linearity is given up to
      35 micrograms/l. Possible interfering substances (haemoglobin, bilirubin,
      triacylglycerol and rheuma factors) do not disturb the assay. The analyte is
      stable under normal storage conditions (+20 degrees C/48 h and +4 degrees C/l
      week) with decrease up to 30% after 3 months at -20 degrees C. Reference value
      for apparently healthy individuals is < 0.1 microgram/l. In plasma cardiac
      troponin I is measured up to 30% depressed compared to serum. Comparison with
      another cardiac troponin I assay (y = 0.92x + 2.42, r = 0.940) and cardiac
      troponin T is good with y = 6.61x - 1.94, r = 0.91 for the first generation
      cardiac troponin T assay and y = 5.59x - 0.68, r = 0.87 for the second generation
      cardiac troponin T assay. In summary, the evaluated assay is fast, easy to
      perform, and can be used not only in a specialized laboratory, but is also
      suitable for emergency laboratory or smaller laboratory units.

PMID- 9189750
TI  - The integrative revolution in couple and family therapy.
AB  - A quiet revolution has resulted in significant movement toward integrative
      practice in couple and family therapy. This article examines the present status
      of integrative methods, highlighting the factors that have led to their broad
      acceptance, issues surrounding the definition of integration and the nomenclature
      used, the content of recent approaches, and specific conceptual developments and
      directions.

PMID- 9189751
TI  - Perceived family criticism and primary care utilization: psychosocial and
      biomedical pathways.
AB  - We explored the relationship of perceived family criticism to subsequent
      healthcare utilization in patients attending a family medicine center. We
      examined: a) the relationship of perceived criticism to subsequent utilization
      for biomedical and psychosocial/somatic problems; b) the mediating effects of
      self-rated mental health and physical function; and c) the mediating effects of
      social support. The analyses were adjusted for age, sex, race, education, health
      insurance, and martial status. Higher perceived criticism predicted more
      psychosocial/somatic and biomedical visits. The relationship of perceived
      criticism with psychosocial/somatic visits was entirely mediated through self
      rated mental health. The relationship of perceived criticism with biomedical
      visits was partly mediated through self-rated physical function and, in part,
      independent. Social support played no role in explaining these relationships.
      Further research is needed to determine whether lowering perceived family
      criticism lowers primary care utilization.

PMID- 9189752
TI  - Factors in Chinese marital process: relationship to marital adjustment.
AB  - This research examined the applicability, in Taiwan Chinese groups, of western
      approaches to conceptualizing and assessing aspects of martial relations. Chinese
      translations of American measures of marital adjustment (the Marital Adjustment
      Test) and marital process (the California Inventory for Family Assessment,
      measuring respondents' perceptions of their spouses' behavior) were developed to
      study a Taiwan Chinese sample of husbands and wives (N = 104 in Taiwan and N = 54
      in the United States). These translations were found to be reliable and for the
      most part to relate as expected. In accordance with Green and Werner's (1996)
      reconceptualization of the cohesion-enmeshment domain, factor analytic results
      yielded independent dimensions consistent with the western constructs of
      intrusiveness and closeness-caregiving. Results also suggested aspects of marital
      process that may distinguish Taiwan Chinese marriages from those among western
      cultures. These findings were interpreted with reference to the impact of
      modernization on Chinese marital relations.

PMID- 9189753
TI  - A brief scale for assessing parental child-rearing practice: psychometric
      properties and psychosocial correlates.
AB  - The development and initial validation of the 20-item Colorado Parental Child
      Rearing Scale (CPCRS) is described, based on three studies of college students,
      including one study that obtained data from students and their parents. The scale
      comprises four 5-item subscales that are largely uncorrelated and that reliably
      assess parental affection, punitiveness, control, and lax discipline. The first
      three of these subscales have been repeatedly found in previous studies of
      parental child-rearing, while the fourth subscale has been found somewhat less
      commonly. Many previously identified relationships linking parental child-rearing
      practice and respondent personality and demographic characteristics were
      confirmed in the present study. Data obtained from parents and siblings yielded
      descriptions of parental child-rearing practice that were generally significantly
      correlated with those obtained from index students. Suggestions for additional
      investigation of parental child-rearing practice are proposed.

PMID- 9189754
TI  - Patterns of sexual coercion in adult heterosexual relationships: an exploration
      of male victimization.
AB  - The sexual coercion of adult males by females in heterosexual relationships has
      received little empirical attention. The purpose of this study was to identify
      and describe such relationships--in comparison with relationships involving the
      sexual coercion of females, of both males and females, and of neither--through
      analysis of data for 3,032 couples that completed the Preparation for Marriage
      instrument (Holman, Busby, & Larson, 1989). Current individual and couple
      characteristics were investigated for male subjects and their partners. The
      results revealed greater deficiencies in relational resources and commitment in
      coercive versus noncoercive couples. In addition, gender differences were noted
      among results for different victim/offender configurations.

PMID- 9189755
TI  - Signal transduction via the histidyl-aspartyl phosphorelay.
AB  - The histidyl-aspartyl phosphorelay, formerly described as the two-component
      system, is the predominant mode of signal transduction in bacteria. Adaptation to
      environmental changes occurs through a sensor histidine protein kinase and a
      response regulator. The histidine protein kinase is usually a transmembrane
      receptor and the response regulator is a cytoplasmic protein. Together the
      histidyl-aspartyl phosphorelay proteins mediate reversible phosphorylation events
      that control downstream effectors. Following autophosphorylation at a conserved
      histidine residue, the histidine kinase serves as a phospho-donor for the
      response regulator. Once phosphorylated, the response regulator mediates changes
      in gene expression or cellular locomotion. The EnvZ-OmpR phosphorelay system in
      Escherichia coli, which monitors external osmolarity and responds by
      differentially modulating the expression of the OmpF and OmpC major outer
      membrane porins, will be described as a model system. While histidine kinases
      were thought to be present only in prokaryotes, they have recently been
      identified in eukaryotic systems. Here, we review the unique and conserved
      features of this growing family of signal transducers.

PMID- 9189756
TI  - Basal level transcription of the human hsp86 gene is directed by intron-based
      elements.
AB  - BACKGROUND: The heat shock response includes the syntheses of three major size
      classes of heat shock proteins (hsps) designated as class 20, 70 and 90 hsps,
      respectively. In contrast to the class 20 and 70 hsp genes, those coding for the
      class 90 hsps are already actively transcribed in the non-induced state. RESULTS:
      We have shown that the increased basal level transcription of the human hsp86
      gene depends on the presence of the first intron. Furthermore, intron 1 of the
      hsp86 gene was also capable of conferring increased basal level transcription on
      the human hsp70 promoter. Finally, the intron I-based sequence elements of the
      hsp86 gene mediated an effective rescue of 5'-truncated hsp70 and hsp86
      promoters. In contrast, such a rescue of inactivated promoters was not obtained
      with the viral SV40 gene enhancer which is often also capable of stimulating
      basal level expression. CONCLUSIONS: Element(s) which direct the basal
      transcription of the human hsp86 gene at normal physiological temperatures are
      located within the first intron of the gene. It is conceivable that this intron
      dependent activation of basal hsp86 transcription reflects a fundamental
      requirement for this protein in the context of cellular growth and metabolism
      under non-stress conditions.

PMID- 9189757
TI  - Molecular properties of the proteasome activator PA28 family proteins and gamma
      interferon regulation.
AB  - BACKGROUND: Recent cDNA cloning of two homologous proteasome activators, PA28
      alpha and PA28 beta, indicated the presence of a structurally related third
      protein, Ki antigen, but a functional relationship between Ki antigen and the two
      PA28 proteins is unknown. Accumulating evidence has implicated an important role
      for PA28 in the major histocompatibility complex (MHC) class I-restricted antigen
      processing pathway. Recently, an immunomodulatory cytokine gamma-interferon
      (gamma-IFN) was found to increase greatly the messages for PA28 alpha and PA28
      beta, but not Ki antigen, in human cells. RESULTS: Ki antigen was co
      immunoprecipitated with the 20S proteasome by anti-proteasome antibody, and
      associated reversibly with the 20S proteasome, as observed for PA28 alpha and
      PA28 beta. Therefore, Ki antigen was renamed PA28 gamma. Anti-PA28 gamma
      antibody, however, did not immunoprecipitate PA28 alpha and PA28 beta. gamma-IFN
      caused an almost complete loss of the PA28 gamma protein in cells without
      affecting its mRNA level, whereas the levels of both mRNA and protein for PA28
      alpha and PA28 beta were coordinately upregulated by gamma-IFN. Finally we showed
      that the human chromosomal genes of PA28 alpha and PA28 gamma were located on
      14q11.2 and 17q21.32-21.33, respectively. CONCLUSION: PA28 gamma (equivalent to
      Ki antigen) is a new member of the PA28 family proteins. It exists as a unique
      homopolymer under non-denaturing conditions. gamma-IFN was found to induce the
      expression of PA28 alpha and PA28 beta, whereas it caused almost complete loss of
      the PA28 gamma protein in cells. The reciprocal expression of the PA28 family
      proteins may imply their involvement in distinct biological processes.

PMID- 9189758
TI  - Proto-oncogene of int-3, a mouse Notch homologue, is expressed in endothelial
      cells during early embryogenesis.
AB  - BACKGROUND: Notch and its homologues are key regulatory receptors of the cell
      fate decision in various developmental processes. The int-3 oncogene was
      originally identified as a frequent target in Mouse Mammary Tumour Virus (MMTV)
      induced mammary tumours and has been regarded as a Notch homologue, based on its
      similarity to the intracellular domain of Notch. Studies with int-3 transgenic
      mice have suggested that the int-3 transgene affects the differentiation capacity
      of stem cells and leads to neoplastic proliferation in epithelial cells. However,
      the exact nature and the in vivo expression pattern of the int-3 proto-oncogene
      are unknown. The function of gene products in embryogenesis is also not clear.
      RESULTS: We isolated cDNA clones corresponding to the proto-oncogene of int-3 and
      analysed its overall structure. The predicted amino acid sequence of the int-3
      proto-oncogene contains the conserved motif found in Notch family receptors.
      Therefore, we name Notch-4 for the int-3 proto-oncogene. However, Notch-4 has
      fewer EGF repeats and shows less similarity to Notch, compared with other
      mammalian Notch homologues. In embryogenesis, the expression of Notch-4 was
      detected in endothelial cells of blood vessels forming tissues such as the dorsal
      aorta, intersegmental vessels, yolk sac vessels, cephalic vessels, heart, vessels
      in branchial arches, and capillary plexuses. In these tissues, Notch-4 expression
      coincided with flk-1, the major regulatory gene of vasculogenesis and
      angiogenesis. We also found that Notch-4 expression was up-regulated in vitro
      during the differentiation of endothelial cells from embryonic stem cells (ES
      cells). CONCLUSION: The endothelial cell specific expression pattern of Notch-4,
      as well as its structural similarity of Notch, suggest that Notch-4 is an
      endothelial cell specific homologue of Notch and it may play a crucial role in
      vasculogenesis and angiogenesis.

PMID- 9189759
TI  - Atonal is a proneural gene for a subset of olfactory sense organs in Drosophila.
AB  - BACKGROUND: The antenna of the adult fruit fly, Drosophila melanogaster, is
      covered with three morphologically distinct types of olfactory sense organs. In
      addition, mechano- and hygro-sensitive receptors are also present on its surface.
      While much has been learnt about the development of peripheral nervous system in
      Drosophila, the mechanisms underlying the development of olfactory sensilla are
      just beginning to be unraveled. The antennal sense organs have several properties
      that make them distinct from other sense organs. While each sensillum type is
      arranged in a well-defined region of the antenna, the position of an individual
      sensillum is not fixed. The development of these sense organs appears to combine
      an initial step of cell recruitment, as in photoreceptors, followed by cell
      lineage mechanisms, as in the development of other external sense organs. The
      earliest step in development, the selection of a sensory organ precursor,
      involves the interaction of proneural and neurogenic genes. The proneural gene
      for the antennal sense organs has been elusive so far. RESULTS: We show that the
      basic helix-loop-helix (bHLH) transcription factor encoded by atonal (ato) is a
      proneural gene for one morphological type of olfactory sensilla on the antenna
      and for all the olfactory sensilla on the maxillary palp. Loss of function and
      overexpression experiments together reveal that ato is both necessary and
      sufficient to specify these sensilla. Immunohistochemical experiments show that
      Ato expresses in a dynamic pattern in the developing antennal disc. CONCLUSIONS:
      Our results demonstrate that ato acts solely in the specification of antennal
      sensilla coeloconica. This along with our previous observation that the AS-C
      genes do not function in antenna allows us to suggest that other proneural genes
      must operate in the specification of sensilla basiconica and trichoidea. Our
      experiment involving overexpression of extramacrochaetae, a negative regulator of
      bHLH encoding genes, results in a significant reduction in the number of all
      three types of antennal sensilla. This suggests that the unidentified proneural
      gene(s) possibly encode bHLH factors.

PMID- 9189760
TI  - High-efficiency stable gene transfer of adenovirus into mammalian cells using
      ionizing radiation.
AB  - We report a novel method for targeting adenovirus-mediated gene delivery. By
      irradiating mammalian cells prior to adenoviral transduction, adenoviral gene
      transfer is greatly improved and the adenoviral genome integrates into cellular
      DNA. In this work, human and rodent cell lines were irradiated and subsequently
      transduced with the adenovirus vector Ad5CMVlacZ. Initial levels of transduction
      were as much as 40-fold higher in irradiated cells, and this improvement in
      transduction was radiation dose dependent. The duration of lacZ expression in
      irradiated cells was also much longer than in nonirradiated cells and reached a
      plateau after 21 days. At doses of 7 Gy, long-term (< 50 day) expression of lacZ
      could be detected in 15% of cells by flow cytometry. This long-lasting expression
      of lacZ was due to viral DNA integration into the host genome. Thus, pretreatment
      of cells with ionizing radiation improves both immediate transduction efficiency
      and duration of transgene expression. This may lead to the development of new
      protocols combining radiation and gene therapy in treating human malignancy.

PMID- 9189761
TI  - Vasomotor dysfunction early after exposure of normal rabbit arteries to an
      adenoviral vector.
AB  - We aimed to investigate whether infection of normal rabbit arteries with a
      recombinant adenovirus vector would result per se in alterations in contractile
      and endothelial functions. In one group of rabbits, right or left femoral and ear
      artery segments were injected in vivo with a replication-deficient adenoviral
      vector expressing a beta-galactosidase (beta-Gal) reporter gene (4 x 10(10)
      pfu/ml) to demonstrate efficient gene transfer. Contralateral arteries were
      injected with the same concentration of a recombinant adenoviral vector carrying
      no transgene (Ad.MLPnull). In another group of animals, Ad.MLPnull was injected
      into the lumen of femoral and ear artery segments. The contralateral arteries
      were used as controls with the injection of vehicle alone. Histochemical
      assessment of gene transfer using beta-Gal activity (group 1) or in vitro
      contractility and endothelial function (group 2) was performed 3 days after
      adenoviral infection. Gene transfer was efficient and reproducible in the
      endothelium and was associated with the presence of inflammatory cells in the
      media. In Ad.MLPnull-injected arteries, in vitro contractile response of femoral
      artery rings to either KCl 60 mM or phenylephrine (10 microM) was reduced to 10.5
      +/- 2.3% (n = 14; p < 0.001) and 8.8 +/- 2.0% (n = 7; p < 0.001) of the control
      values, respectively. Furthermore, in arteries injected with Ad.MLPnull, the
      endothelium-dependent relaxation produced by acetylcholine (10 microM) was
      virtually abolished. Similarly, the relaxant effects of the alpha 2
      adrenoreceptor agonist UK14304 (1 microM) or the Ca2+ ionophore A23187 (1 microM)
      were also abolished. By contrast, sodium nitroprusside (10 microM) was still able
      to relax adenovirus-infected arteries. We conclude that infection with a
      recombinant adenoviral vector can induce early severe vasomotor alterations in
      both contractile function and endothelium-mediated relaxation of normal rabbit
      arteries.

PMID- 9189762
TI  - Construction of retroviral vectors carrying human CD3 gamma cDNA and
      reconstitution of CD3 gamma expression and T cell receptor surface expression and
      function in a CD3 gamma-deficient mutant T cell line.
AB  - CD3 gamma, a subunit of the T cell receptor-CD3 (TCR/CD3) complex, helps to
      support surface TCR/CD3 expression and participates in signal transduction for
      gene induction after antigen recognition by T lymphocytes, and in TCR/CD3 down
      modulation. Humans with primary immunodeficiencies caused by inherited mutations
      in the CD3 gamma gene or in the gene encoding epsilon CD3e, another subunit of
      TCR/CD3 complex, have been previously reported. To develop a gene therapy
      protocol for CD3-deficient patients, CD3 gamma cDNA was orientationally inserted
      into two retroviral vectors (LNCX and LXSN), which resulted in recombinant
      vectors LNCG and LGSN, respectively. Two vector producer cell lines Am12/LNCG and
      Am12/LGSN were established from packaging cells GP+envAm12. Their mean viral
      titers were 6.5 x 10(6) and 2.0 x 10(7) cfu/ml, respectively, as shown by an
      improved retroviral vector production and transduction method that increases
      titers around five-fold over conventional methods. The presence of helper virus
      in vector stocks was tested by marker rescue assay and found to be < 1 cfu/ml.
      Southern blot analysis showed that multiple copies of the vectors were present in
      the genome of high-titer producers and that both vectors could transfer CD3 gamma
      cDNA into the genome of 3T3 cells. The vectors were used to correct in vitro a
      CD3 gamma-deficient Jurkat mutant cell line lacking TCR/CD3 expression and termed
      JGN (for Jurkat gamma negative). Both vectors increased TCR/CD3 expression in JGN
      (normally 2% using WT31 monoclonal antibody) to 34% and 37%, respectively, in
      G418-selected 3-week bulk cultures. Two clones from transduced JGN cells termed
      JGN/LNCG13 and JGN/LNCG15, with high TCR/CD3 expression (88% and 79%,
      respectively), were selected for further analyses. First, CD3 gamma protein
      reconstitution was demonstrated by immunoprecipitation. Second, interleukin-2
      production after TCR/CD3 engagement and TCR/CD3 down-modulation in response to
      phorbol myristate acetate were shown to be comparable to wild-type Jurkat cells.
      We conclude that LNCG and LGSN may be useful for gene therapy purposes.

PMID- 9189763
TI  - Adenoviral vector-mediated gene expression in the nervous system of
      immunocompetent Wistar and T cell-deficient nude rats: preferential survival of
      transduced astroglial cells in nude rats.
AB  - In the present paper, we examined the effect of the adenoviral vector dosage, the
      role of T cells, and the influence of the presence of replication-competent
      adenovirus (RCA) in adenoviral vector stocks, on the efficacy of adenoviral
      vector-directed transgene expression in the facial nucleus of immunocompetent
      Wistar and athymic nude rats. A small number of motor neurons and glial cells was
      transduced at low dosages of viral vector (1 x 10(6) pfu) and in the absence of
      RCA, and transgene-expressing cells persisted throughout the 3-week period of
      observation. Intraparenchymal infusion of 2 x 10(7) pfu of a recombinant
      adenoviral vector free of RCA was required for optimal transduction of facial
      motor neurons. In Wistar rats, a biphasic immune response occurred at higher
      dosages of the vector (5 x 10(6) and 2 x 10(7) pfu) that was characterized by
      early infiltration of macrophages and the occurrence of T cells during the second
      week after injection of the vector. The immune response was associated with the
      loss of transduced neural cells. In nude rats, administration of an adenoviral
      vector free of RCA resulted in a macrophage response comparable to that in the
      Wistar rat and long-term survival of transduced astroglial cells. However,
      transduced motor neurons degenerated according to a similar time course as
      observed in Wistar rats. Small amounts of RCA (2 x 10(5) pfu) injected with 2 x
      10(7) pfu recombinant viral vector particles resulted in an accelerated T cell
      response and a rapid elimination of transduced cells within 1 week in Wistar
      rats, whereas in nude rats transgene expression continued during this period.
      Taken together, these observations suggest that at the high viral vector loads
      necessary to achieve optimal transduction of the facial nucleus, T cells play a
      role in the degeneration of adenoviral vector-transduced astroglial cells. The
      adverse effects on neurons appear to be due to the observed inflammatory response
      or to direct adenoviral vector toxicity.

PMID- 9189764
TI  - Gene therapy for metastatic brain tumors by vaccination with granulocyte
      macrophage colony-stimulating factor-transduced tumor cells.
AB  - We have developed an ex vivo gene therapy paradigm for the treatment of brain
      tumors using granulocyte-macrophage colony-stimulating factor (GM-CSF). Murine
      B16 melanoma cells were infected with MFG recombinant retrovirus containing the
      mouse GM-CSF cDNA. Subcutaneous vaccination of syngeneic mice with irradiated GM
      CSF-secreting B16 melanoma cells was capable of completely protecting animals
      against subsequent intracranial B16 tumor inoculation, with up to 5 x 10(3)
      cells. Histologic evaluation revealed the presence of neutrophils, eosinophils,
      and lymphocytes, including CD4+, CD8+, and CD45R+ cells, in the intracerebral
      inoculation site, peaking 4 days after intracranial inoculation. In contrast,
      nonvaccinated animals or animals vaccinated with irradiated, nontransduced B16
      cells succumbed to intracranial tumor within 3 weeks after inoculation. Treatment
      of established intracranial B16 melanoma tumors with subcutaneous injection of
      irradiated GM-CSF-secreting B16 cells significantly delayed death, as compared to
      injection of irradiated nontransduced B16 cells or no treatment. In addition,
      treatment of established intracerebral GL261 gliomas by vaccination with
      irradiated GM-CSF-secreting B16 cells mixed with irradiated, transduced, or
      nontransduced GL261 cells also extended survival. These B16/GL261 co-vaccinations
      also improved outcome and, in some cases, induced immunological memory that
      protected survivors from subsequent intracranial challenge with GL261 tumor
      cells. These findings indicate that peripheral vaccination with irradiated tumor
      cells in the presence of GM-CSF-producing cells can initiate a potent antitumor
      immune response against intracranial neoplasms.

PMID- 9189765
TI  - Granulocyte-macrophage colony-stimulating factor and B7-2 combination immunogene
      therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme
      model.
AB  - Glioblastoma multiforme is the most common primary central nervous system
      neoplasm. Its dismal prognosis has led to investigation of new treatment
      strategies such as immunogene therapy. We transduced the human glioblastoma cell
      line D54MG in vitro with genes encoding the proinflammatory cytokine granulocyte
      macrophage colony-stimulating factor (GM-CSF), the T cell co-stimulatory molecule
      B7-2, or both (in a bicistronic vector) via retroviral vectors. Therapeutic gene
      expression by D54MG was high after transduction and selection (30 ng/10(6)
      cells/day for GM-CSF and > 2 orders of magnitude fluorescence shift on flow
      cytometry for B7-2). The effect of GM-CSF and/or B7-2 transduction on D54MG tumor
      growth in vivo was monitored in a novel allogeneic human peripheral blood
      lymphocyte-severe combined immunodeficiency mouse (Hu-PBL-SCID) model. GM-CSF- or
      B7-2-transduced tumors showed growth suppression in hu-PBL-reconstituted mice
      compared to untransduced and/or unreconstituted controls. Growth suppression was
      greatest for B7-2. Furthermore, vaccination with irradiated GM-CSF/B7-2
      transduced tumor cells markedly inhibited growth of wild-type tumors at distant
      sites. Thus, this study illustrates a potential gene therapy strategy for
      glioblastoma multiforme patients using GM-CSF and/or B7-2 transduced tumor
      vaccines. Although extension of these allogeneic studies to an autologous system
      is critical, this is the first demonstration of in vivo efficacy of combination
      GM-CSF and B7-2 immunogene therapy for human glioblastoma multiforme.

PMID- 9189766
TI  - Alveolar macrophages inhibit retrovirus-mediated gene transfer to airway
      epithelia.
AB  - Gene transfer with integrating vectors such as recombinant retrovirus has the
      potential to correct inherited lung diseases permanently. As a gene therapy
      target, the pulmonary epithelium presents several challenges to vector delivery
      in vivo. Many of the host defenses that have evolved to prevent infection from
      inhaled bacteria or viruses represent potential barriers to gene transfer to the
      lung. We performed in vitro studies to determine whether two components of the
      innate immune system of the lung, airway surface fluid and alveolar macrophages,
      inhibit retroviral gene transfer to airway epithelia. Human alveolar macrophages
      obtained by bronchoalveolar lavage from normal subjects were left untreated or
      activated with lipopolysaccharide (LPS) for 3 hr in the presence of subconfluent
      human bronchial epithelial cells (HBE); than 4 x 10(5) cfu DA-luciferase
      retrovirus was added. Three days after infection, luciferase activity was
      measured in cell lysates. When the epithelial cells were co-cultured with LPS
      activated macrophages, retroviral gene transfer to HBE cells was reduced by
      approximately 60%. Nonactivated macrophages decreased the transfection to
      approximately 55% of control values. In control experiments with either activated
      or inactivated macrophages but without epithelia, no luciferase activity was
      detected, suggesting that terminally differentiated alveolar macrophages are not
      infected by the recombinant retrovirus. Pretreatment of alveolar macrophages with
      dexamethasone restored gene transfer to approximately 60% of control values. In
      contrast, incubation of retrovirus with airway surface fluid had no inhibitory
      effect on gene transfer. These experiments document that AM inhibit retrovirus
      mediated gene transfer to airway epithelia in vitro, and may represent a barrier
      to retroviral gene transfer in vivo. These barriers may be overcome, at least
      partially, with pharmacological agents.

PMID- 9189767
TI  - Transient immunosuppression with deoxyspergualin improves longevity of transgene
      expression and ability to readminister adenoviral vector to the mouse lung.
AB  - Animal studies have suggested that the clinical usefulness of recombinant
      adenoviruses (Ad) as vectors for therapeutic gene delivery may be limited by
      their immunogenicity. Neutralizing antibodies elicited by capsid proteins reduce
      the efficiency of vector readministration whereas cytotoxic T lymphocytes (CTLs)
      directed against viral proteins and/or immunogenic transgene products expressed
      by transfected cells have the potential to limit persistence of expression. In
      this study, transient administration of the novel immunosuppressant
      deoxyspergualin (DSG) was found to inhibit the development of both humoral and
      cell-mediated immune responses against Ad vector delivered intranasally. DSG
      treatment of primed mice previously exposed to wild-type Ad impaired the
      development of antibodies in response to a secondary and even tertiary challenge
      with Ad vector. As a result, improved gene transfer was obtained upon subsequent
      administration of a beta-galactosidase (beta-Gal)-encoding Ad vector. Short-term
      administration of DSG also depressed the activation of CD4+ and CD8+ T
      lymphocytes as assessed by measurement of antigen-specific proliferation and CTL
      activity, respectively. The marked suppression of CTL activity against Ad vector
      in DSG-treated mice correlated with improved persistence of transgene expression
      in the lung.

PMID- 9189768
TI  - Gene therapy for peritoneal dissemination of pancreatic cancer by liposome
      mediated transfer of herpes simplex virus thymidine kinase gene.
AB  - Peritoneal dissemination is one of the most common complications of the
      malignancies of the digestive system, such as gastric or pancreatic cancers. Yet,
      no effective therapy has been established so far to alleviate this devastating
      and often fatal end-stage condition. Here we describe a novel approach of
      intraperitoneal (i.p.) lipofection of a suicidal gene to the pancreatic cancer
      cells in a mouse peritoneal dissemination model. A human pancreatic cancer cell
      line, PSN-1, was inoculated into the peritoneal cavity of nude mice. Eight days
      later, a herpes simplex virus thymidine kinase (HSV-TK) gene expression plasmid
      under a potent hybrid promoter CAG was injected as a DNA-lipopolyamine complex.
      Ganciclovir (GCV) was then administered for 8 days, and the mice were examined
      for tumor development at the 24th day after the tumor inoculation. Although all
      24 control mice showed macroscopic peritoneal dissemination and solid tumors on
      the pancreas, 8 of the 14 mice treated with HSV-TK and GCV were free of tumors,
      and only a few small tumors were observed in the remaining 6 mice. Treatment
      related toxicity was not observed. The semiquantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis suggested that the HSV-TK transgene
      was expressed in about 10% of tumor cells but not in the normal pancreas or in
      the small intestine. When the lacZ gene was transduced in place of the HSV-TK
      gene, the blue-stained cells were identified only in tumor nodules and not in
      normal organs. This preclinical study suggests the therapeutic feasibility of the
      i.p. lipofection-based suicidal gene/prodrug strategy for peritoneal
      dissemination of pancreatic cancer.

PMID- 9189769
TI  - Defective HIV-1 provirus encoding a multitarget-ribozyme inhibits accumulation of
      spliced and unspliced HIV-1 mRNAs, reduces infectivity of viral progeny, and
      protects the cells from pathogenesis.
AB  - A HeLa T4 cell line containing a defective human immunodeficiency virus type 1
      (HIV-1) DNA (HD4) was isolated. After transactivation with Tat, the HD4 DNA was
      transcribed into a single 3.7-kb mRNA that encodes a chimeric CD4/Env protein and
      a multitarget-ribozyme directed against multiple sites within the gp120 coding
      region of HIV-1 RNA (Chen et al., 1992). Early steps in HIV infection such as
      entry, reverse transcription, and proviral DNA formation were not affected in HD4
      cells, and HD4 was efficiently transactivated after either HIV-1 or HIV-2
      infections. HIV-2, which lacks all of the HIV-1-specific ribozyme target sites,
      replicated to high levels in HD4 cells whereas HIV-1 replication was selectively
      inhibited. Despite a reduced accumulation of all HIV-1 transcripts,
      transactivation of HD4 was efficient. Surprisingly, the most abundant, multiply
      spliced mRNAs were reduced even though they lack all of the ribozyme target
      sites. These results strongly suggest that the ribozyme co-localizes with
      unspliced HIV-1 pre-mRNA and/or genomic HIV-1 RNA in the nucleus. Cleavage of
      these precursor RNAs explains the reduction of all spliced and unspliced HIV-1
      RNAs. Cleavage of genomic RNA probably contributed to the three-fold reduction in
      the infectivity of viral progeny. Thus, the HD4 ribozyme RNA functioned as a
      ribozyme in the nucleus and as a mRNA for a chimeric CD4/Env protein in the
      cytoplasm. Its unusual large size for a ribozyme (3.7 kb) indicates that, in the
      future, other antiviral proteins, like negative transdominant mutant HIV-1
      proteins, may also be encoded to increase its antiviral potential in a gene
      therapy approach.

PMID- 9189771
TI  - Chronic pelvic pain in women--gastroenterological, gynaecological or
      psychological?
AB  - Women with chronic pelvic pain form a substantial part of the workload of
      gynaecologists, gastroenterologists and surgeons. Each investigates with their
      own diagnostic bias but the source of pain often remains obscure, with a lack of
      abnormal findings or failure of symptom resolution despite treatment of
      identified pathology. The patient's physical and social disability may become
      compounded by diagnostic confusion, and by prolonged and ineffective treatments
      including surgery. The end result is often a sense of helplessness in both the
      patient and the physician.

PMID- 9189770
TI  - Construction and biological characterization of an interleukin-12 fusion protein
      (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated
      virus.
AB  - Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on
      lymphocytes and natural killer cells and has been shown to have promise for the
      immunotherapy of cancer. The combination of the immune costimulatory molecule
      B7.1 and IL-12 has been shown to be synergistic for T cell activation. By
      transfecting tumor cells with both IL-12 and B7.1 cDNAs, it may be possible to
      use these modified targets as vaccines. A major obstacle in designing a vector to
      deliver these genes results from the structure of IL-12. Functional IL-12 is a
      heterodimer composed of two distinct subunits that are encoded by separate genes
      on different chromosomes. Production of functional IL-12 requires the coordinated
      expression of both genes. This presents several problems in vectors, particularly
      those in which additional genes, either a co-stimulatory gene or a selectable
      marker, are inserted. Therefore, we have constructed a single cDNA that encodes a
      single-chain protein, called Flexi-12, which retains all of the biological
      characteristics of recombinant IL-12 (rIL-12). The monomeric polypeptide Flexi-12
      is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce
      PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by
      preincubation, enhance the killing of K562 targets by PBLs. These phenomena are
      in a dose-dependent manner comparable to that seen with rIL-12. We have also
      shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has
      been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at
      levels similar to those seen with rIL-12. We have packaged Flexi-12 into a
      recombinant adeno-associated virus (AAV) and used this vector to infect acute
      myeloid leukemic (AML) blasts. Infected AML blasts produced between 2 and 6 ng of
      IL-12/10(6) cells per ml per 48 hr. These studies also confirm that AAV is an
      efficient delivery vehicle for cytokines to leukemic cells. Direct analysis of
      these modified cells acting as tumor vaccines is underway.

PMID- 9189772
TI  - The effect of prostaglandin E1 on experimental colitis in the rat.
AB  - Prostaglandin E1 (PGE1) is known to have a strong vasodilator effect and to block
      coagulation and inflammation in high concentrations. The aim of this study has
      been to investigate whether PGE1 has an inhibitory effect on inflammation in
      experimental colitis. Experimental colitis was produced by rectal instillation of
      10% acetic acid in 60 rats. These were divided into prostaglandin (PG) (n = 30)
      and control groups (n = 30). Twelve hours later, an intraperitoneal injection of
      2 micrograms PGE1 in 1 ml saline was given to the PG group and 1 ml saline to the
      control group. This was repeated daily and the animals were sacrificed in groups
      of 10 on the 3rd, 7th and 10th day. Histopathological examination and
      hydroxyproline determination for assessment of collagen synthesis were performed.
      PGE1 significantly decreased inflammation on third day with the hydroxyproline
      level significantly higher in the PG group compared with the control group (p <
      0.05). This difference was however not significant at the 7th and 10th day. The
      present study supports a beneficial role for prostaglandin E1 in reducing the
      severity of colonic inflammation following chemically induced colitis but only in
      the early stages of development.

PMID- 9189773
TI  - Are interpretations of video defecographies reliable and reproducible?
AB  - Video defecography is a dynamic investigation which can influence surgical
      decision making in constipated patients. A study was therefore undertaken to
      assess the inter and intraobserver variability in video defecography.
      Specifically, we sought to assess the interpretation of video defecographies by a
      group of observers with the same training, guidelines and standards. To determine
      interobserver variation, four independent observers, two blinded to the patient's
      history, reviewed 100 randomly sequenced video defecographies performed in
      constipated patients. The presence or absence of sigmoidocele, rectocele,
      intussusception or prolapse was noted. Adequate or improper function of the
      puborectalis, anal canal opening, anorectal angle (ARA) and grade of emptying of
      the rectum were also assessed. Two weeks after the initial assessment,
      intraobserver variation was determined by a repeat blinded review of unlabelled
      randomly sequenced studies. The results of interobserver accuracy for
      sigmoidoceles, rectoceles, intussusception, rectal prolapse, rectal emptying,
      opening of the anal canal, puborectalis contraction and straightening of the ARA
      and rectal emptying were 89.5%, 46.0%, 87.5%, 97.5%, 86.5%, 88.5%, 83.0%, and
      80.0%, respectively. The intraobserver variations were 88.5%, 83.8%, 80.5%,
      94.5%, 77.0%, 84.8%, 80.5% and 85.5%, respectively. Prior knowledge of the
      patient's history did not significantly influence the outcome. In summery, video
      defecography has an overall accuracy of 83.3% and as such is a valid tool in
      assessing constipated patients.

PMID- 9189775
TI  - Endorectal ultrasonography in the follow-up of rectal cancer. Is it a better way
      to detect early local recurrence?
AB  - After curative surgery for rectal cancer, diverse protocols are used in order to
      detect early possible local recurrence. Our objective was to compare the results
      obtained by the endorectal ultrasonography (EUS) with other means of assessment.
      From 1988 to 1995, 140 patients have undergone curative surgery for rectal
      cancer. The pathological and sonographic lesions were evaluated according to the
      TNM classification. In 21 patients a local recurrence was diagnosed: 5 of those
      21 were corresponding to T 3-4, N 0 and 16 to T 2-4, N 1 stage. All 21 showed
      evidence of local recurrence by EUS examination, 14 by digital rectal
      examination, 16 by colonoscopy, 18 by computed tomography, and the
      carcinoembryonic antigen level was high in 13 cases. In 12 patient who were
      asymptomatic EUS was positive in 12, digital rectal examination in 5, computer
      tomography in 9, colonoscopy in 8, and the CEA was increased in 4. Re-resection
      was possible in 15 cases, 6 with curative approach and 9 palliative. These
      findings suggest that EUS in care accurate in the early detection of local
      recurrence compared to other means of assessment review of the. The limited
      number of patients studies. Main form of assessment required further evaluation.

PMID- 9189774
TI  - The effects of the pharmacological manipulation of postoperative intestinal
      motility on colonic anastomoses. An experimental study in a rat model.
AB  - INTRODUCTION: The aim of the study was to determine the effects of
      pharmacological manipulation of postoperative intestinal motility on the
      resistance of colonic anastomoses. MATERIALS AND METHODS: Seventy-one Sprague
      Dawley rats were divided into three groups: Group 1 (n = 20; colonic
      anastomosis+1 cc of saline solution subcutaneously, daily); Group 2 (n = 29;
      colonic anastomosis+1.2 mg/100 g body weight metoclopramide in 1 cc
      subcutaneously, daily); and Group 3 (n = 22; colonic anastomosis+2 mg/100 g body
      weight hyoscine N-butyl-bromide in 1 cc subcutaneously, daily). Surviving rats
      (20 in each group) were sacrificed 4 days after surgery and adhesions were
      evaluated. Each segment containing an anastomosis was removed and the bursting
      pressure was determined. RESULTS: The cause of death during the early
      postoperative period was dehiscence in 8 cases (7 in Group 2 and 1 in Group 3).
      General adhesion scores in Group 2 were higher than in Group 3 (P = 0.003). The
      score for adhesions to the anastomosis in Group 1 was higher than in Group 2, but
      no statistically significant difference was found. Bursting-pressure was
      significantly lower in Group 2 than in other groups (P = 0.001). In all cases
      leakage of dye was observed at the anastomosis. CONCLUSION: The use of
      metoclopramide (a gastrointestinal prokinetic agent) during the early
      postoperative period was associated with an increase in dehiscence in colonic
      anastomosis and, when animals survived, there was a significant decrease in
      anastomotic resistance. Hyoscine (an inhibitor of gastrointestinal motility) did
      not improve the healing of anastomoses.

PMID- 9189776
TI  - Continence after colorectal reconstruction following resection: impact of level
      of anastomosis.
AB  - In 48 patients who had undergone anterior resection for rectal cancer with
      straight colorectal reconstruction, clinical and manometric results were
      correlated with the level of anastomosis. Patients were divided into four groups
      by anastomotic level: < or = 3, 4-6, 7-9, and > or = 10 cm. Functional outcome
      with regard to frequency of bowel movements, minor leakage, fecal incontinence.
      ability to defer stool and to differentiate consistency showed increasing
      impairment the lower the anastomotic level. Frequency, leakage owing to the
      inability to defer stool, incontinence for solid stool, inability to discriminate
      flatus from stool, and incomplete emptying were significantly different (P <
      0.05) between the patients with an anastomotic level between 3-6 cm and between 7
      9 cm. Manometric data revealed no trend or significant differences among the
      groups with regard to anal resting pressure and maximal and median squeeze
      pressure. Rectoanal inhibitory reflex was abolished in 60% of the patients. Clear
      changes, with a trend toward reduced function with lower anastomotic levels, were
      seen in the volume that produced a feeling of urgency, maximal tolerable volume,
      and neorectal compliance (between anastomotic levels 7-9 and > or = 10 cm the
      differences were significant; P < 0.05). Analysis by length of residual rectum (<
      1.5, 1.5-4.0, 4.1-6.5, > 6.5 cm) demonstrated similar findings, suggesting that
      impaired function after rectal resection is due to reduced function of the
      neorectum. Thus, as much residual rectum as possible should be preserve without
      risking cure. If the level of the anastomosis is expected to be below 6 cm, or if
      the residual rectum is less than 4 cm, the construction of a colon pouch to
      increase neorectal capacity should be considered.

PMID- 9189777
TI  - A preliminary comparison of a consecutive series of open versus laparoscopic
      abdomino-perineal resection for rectal adenocarcinoma.
AB  - AIM: To compare a consecutive series of patients who underwent laparoscopic
      abdomino-perineal resection (LAPR) versus conventional open abdomino-perineal
      resection (CAPR). MATERIAL AND METHODS: Sixteen patients (8 females) and 11
      patients (4 females) underwent LAPR and CAPR respectively. RESULTS: The median
      operative time was 110 (65-210) mins and 100 (80-185) mins for LAPR and CAPR
      respectively (P = 0.43). The median amount of blood loss were 200 (100-1000) mls
      and 100 (60-800) mls for LAPR and CAPR respectively. There was no significant
      difference in the need for post operative analgesics and time to first stoma
      function but the LAPR group showed significant improvement in starting fluids,
      diet, ambulation and discharge from hospital. CONCLUSION: The laparoscopic
      technique may be an acceptable alternative to conventional abdomino-perineal
      resection for the patient requiring anal resection for rectal cancer.

PMID- 9189778
TI  - Defaecography in patients with irritable bowel syndrome and healthy volunteers.
AB  - BACKGROUND: In patients with IBS, many symptoms have their origin in the recto
      anal segment, with motility changes in the rectum and in the internal anal
      sphincter, and alterations in rectal sensitivity. However, up to now, it is not
      known if these clinical and physiological changes are equated with morphological
      changes in the recto-anal segment. METHODS: Sixteen consecutive patients with IBS
      (mean age 22, range 18-33 years; 13 females) and 10 healthy volunteers (mean age
      34.5, range 19-50 yr.; 6 males) were evaluated prospectively with defaecography.
      RESULTS: 1) Anorectal angle: No significant differences were observed in the
      anorectal angle during rest (91.6 +/- 3.5 degrees vs 92.6 +/- 2.5 degrees) and
      during defaecation (92 +/- 5.5 degrees vs 98.7 +/- 2.6 degrees) between patients
      with IBS and healthy volunteers. However, patients with IBS were unable to widen
      the angle during defaecation, remaining the same at rest (91.6 +/- 3.5 degrees)
      as during defaecation (92 +/- 5.5 degrees). IBS patients with constipation (n =
      2) compared to those with normal frequency defaecation (n = 13) showed no
      significant differences at rest (95 +/- 6 vs 89.8 +/- 4.1 degrees) and during
      defaecation (100 +/- vs 88.9 +/- 6.4 degrees). Healthy volunteers widened the
      angle by more than 5 degrees during defaecation. 2) Perineometry: although not
      significant, patients with IBS had less perineal descent during the simulated
      defaecation (1.98 +/- 0.37 cm) than healthy subjects (2.1 +/- 0.3 cm).
      Nevertheless, during squeeze there was significantly less mobility or perineal
      descent in patients with IBS than in control subjects (0.21 +/- 0.17 vs 0.95 +/-
      0.21 cm; P = 0.01). CONCLUSIONS: The findings of this study suggest that patients
      with IBS as a whole, whether constipation predominant or not, showed changes in
      pelvic-floor mobility.

PMID- 9189779
TI  - "Life insurance and inflammatory bowel disease: is there discrimination against
      patients?".

PMID- 9189780
TI  - Dietary practices of South African ultradistance runners.
AB  - Training (T) and prerace (PR) dietary intakes of male and female athletes
      participating in a 90-km ultramarathon and the usual diets of matched, sedentary
      controls were investigated using 24-hr dietary records. Supplement use, mean
      weekly training distance, and race performance times were recorded. Macro- and
      micronutrient intakes were analyzed using computerized nutritional analysis
      programs. Total mean energy intake in the T and PR diets of the runners was 10.1
      and 12.8 MJ in the men (n = 150) and 7.5 and 9.1 MJ in the women (n = 23). Mean
      relative contribution of CHO to the runners' total kilojoule intake increased
      from 50.0 and 49.5% in the T diets to 57.7 (p < .05; n = 153) and 56.4% (p < .05;
      n = 23) in the PR diets of male and female runners, respectively, and energy
      boosting supplements were included in the PR diets of 48% of female and 59% of
      male runners. Seventy-eight percent of female and 62% of male runners used
      vitamin and mineral supplements in their T diets as opposed to 39% of female and
      28% of male controls. No statistically significant relationship was found between
      total kilojoule, CHO, fat, protein, and selected micronutrient intake during the
      3 days before the race and performance in the 90-km event in runners of
      homogenous training status and gender.

PMID- 9189781
TI  - Influence of sodium replacement on fluid ingestion following exercise-induced
      dehydration.
AB  - This study investigated the hypothesis that addition of Na+ to a rehydration
      beverage would stimulate drinking and augment restoration of body water in
      individuals dehydrated during 90 min of continuous treadmill exercise in the
      heat. Following a 3.0 +/- 0.2% decrease in body weight (BW), 6 subjects sat in a
      thermoneutral environment for 30 min to allow body fluid compartments to
      stabilize. Over the next 3 hr, subjects rehydrated ad libitum using either
      flavored/artificially sweetened water (H2O-R) or a flavored, 6% sucrose drink
      containing either 25 (LNa(+)-R) or 50 (HNa(+)-R) mmol/L NaCl. Results
      demonstrated that rapid removal of the osmotic stimulus, during H2O-R, and the
      volume-dependent dipsogenic stimuli, during HNa(+)-R, are important factors in
      limiting fluid intake during rehydration, compared to LNa(+)-R. It was also found
      that the pattern of fluid replacement and restoration of fluid balance following
      dehydration is influenced by the dehydration protocol used to induce the loss in
      total body water and the sodium content of the rehydration beverage.

PMID- 9189782
TI  - Oxidation of 13C-glucose and 13C-fructose ingested as a preexercise meal: effect
      of carbohydrate ingestion during exercise.
AB  - The oxidation of 13C-labeled glucose and fructose ingested as a preexercise meal
      between 180 and 90 min before exercise was measured on 6 subjects when either a
      placebo or sucrose was ingested during the exercise period. Labeled hexose
      oxidation, which occurred mainly during the first hour of exercise, was not
      significantly modified when sucrose was ingested, but exogenous glucose oxidation
      was significantly higher than exogenous fructose oxidation in both situations.
      The results suggest that the absorption rate of exogenous hexoses was high when
      exercise was initiated but diminished thereafter, and that glucose and fructose
      released from sucrose ingested during exercise did not compete with glucose or
      fructose ingested before exercise for intestinal absorption, for conversion into
      glucose in the liver (for fructose), or for uptake and oxidation of glucose in
      peripheral tissues. However, as already shown, in terms of availability for
      oxidation of carbohydrates provided by the preexercise meal, glucose should be
      favored over fructose.

PMID- 9189783
TI  - Glycemic and insulinemic responses to multiple preexercise carbohydrate feedings.
AB  - This investigation was undertaken to determine whether consuming several small
      feedings of preexercise carbohydrate (CHO), rather than a single bolus, would
      affect blood glucose and insulin responses during rest and exercise. Eight
      trained cyclists ingested 22.5, 45, or 75 total g maltodextrin and dextrose
      dissolved in 473 ml of water or an equal volume of placebo (PL). Drinks were
      divided into four portions and consumed at 15-min intervals in the hour before a
      120-min ride at 66% VO2max. Serum glucose values were elevated by the CHO
      feedings at rest and fell significantly below baseline and PL at 15 min of
      exercise. However, glucose concentrations were similar in each of the CHO trials.
      Insulin concentrations also increased rapidly during rest, then fell sharply at
      the onset of exercise. The findings demonstrate that CHO consumed within an hour
      before exercise, even when taken in several small feedings, can produce transient
      hypoglycemia near the onset of exercise. Additionally, the magnitude of the
      response appears to be unrelated to either the amount of CHO ingested or the
      insulin response.

PMID- 9189785
TI  - Gastric emptying and plasma deuterium accumulation following ingestion of water
      and two carbohydrate-electrolyte beverages.
AB  - The purpose of this study was to compare the gastric emptying rates (GER) of
      water, a 6% carbohydrate (CHO) beverage, and a 20% CHO beverage and to contrast
      those rates against the rate at which deuterium oxide in the drinks accumulated
      in plasma (DAR) following beverage ingestion. Ten subjects (8 males, 2 females)
      cycled at 60% VO2max for 70 min; at 13 min, the subjects ingested 400 ml of one
      of the beverages. The GER and DAR of water and 6% CHO were similar, while GER and
      DAR were both significantly slowed by ingestion of 20% CHO. Although there was a
      significant correlation (r = .63, p < .05) between GER and DAR, only 40% of the
      variation in DAR could be accounted for by variation in GER. These data support
      the contention that DAR is partially determined by GER, with differences in the
      rate of fluid absorption across the intestine and other factors accounting for
      the remaining variation in DAR.

PMID- 9189784
TI  - The effect of creatine supplementation on two 700-m maximal running bouts.
AB  - We investigated the effect of creatine supplementation on maximal running
      performance in a simulated track competition. Twelve competitive male runners
      were assigned to either a placebo or creatine supplementation group. Both groups
      completed two maximal 700-m running bouts 60 min apart on an outdoor track. A
      second identical trial was performed 7 days later, and for 5 days prior to the
      second trial, subjects ingested 20 g.day-1 of either creatine monohydrate or a
      placebo. Subjects in the placebo group ran 110.2 +/- 3.5 s and 110.4 +/- 3.0 s
      for the first trial and 108.5 +/- 2.9 s and 108.0 +/- 1.7 s for the second trial,
      while the creatine group ran 109.9 +/- 3.2 s and 110.4 +/- 3.6 s for the first
      trial and 109.7 +/- 3.3 s and 107.8 +/- 2.2 s for the second trial. There were no
      significant differences between groups by trial or Trial X Time for running time,
      postexercise blood lactate concentration, or body weight (p > .05). We concluded
      that creatine supplementation does not enhance performance of single or twice
      repeated maximal running bouts lasting 90-120 s.

PMID- 9189786
TI  - Is potassium needed in sports drinks for fluid replacement during exercise?

PMID- 9189787
TI  - Thoracoscopic dissection of the esophagus for cancer.
AB  - Eighteen patients affected by a resectable intramural tumor of the esophagus have
      undergone esophagectomy with thoracoscopic dissection of the esophagus in the
      last 4 years. All patients had a relative contraindication to transthoracic
      esophagectomy with radical lymphadenectomy. All esophagectomies were completed
      thoracoscopically and reconstruction of the digestive tract was performed in 17
      cases through cervical gastroplasty and in 1 case through cervical coloplasty.
      One cirrhotic patient died in the postoperative period due to cervical
      anastomotic leak. Six other patients experienced a postoperative complication
      (mortality rate 5.5%; morbidity rate 33.3%). After a median follow up of 17
      months, 14 patients are alive without evidence of disease. One patient, who had
      excision of a cutaneous metastasis at a trocar insertion site 6 months
      postoperatively, eventually died with locoregional recurrence 14 months
      postoperatively. Another patient died 20 months after surgery with mediastinal
      recurrence. One patient died 28 months postoperatively after massive hematemesis
      with a suspect abdominal recurrence. The results of the present series and those
      reported by other authors do not seem to indicate presently evident advantages
      from the minimally invasive procedure during resection of the esophagus for
      cancer. At the present time, no indication to this procedure exists for standard
      clinical use; wider randomized trials and longer follow-up to be performed only
      in selected centers are needed to further evaluate the procedure.

PMID- 9189788
TI  - Thoracoscopic resection of benign tumours of the esophagus.
AB  - Thoracoscopic excision of an esophageal leiomyoma was successfully performed in 5
      patients. The tumours were enucleated easily without intraoperative
      complications. A patient in whom the muscular layer was not sutured after removal
      of the myoma, one year after the operation presented an esophageal
      pseudodiverticulum requiring a thoracotomy for resection. This new procedure
      which reduces the operative trauma and postoperative pain and allows quick
      recovery is described.

PMID- 9189789
TI  - The role of thoracoscopic lymph node staging in esophageal cancer.
AB  - BACKGROUND: Unlike mediastinoscopy in lung cancer, there exists no standard
      minimally invasive test to stage esophageal cancer. If it were possible to obtain
      exact preoperative staging in esophageal cancer, patients could be separated
      prospectively to receive adjuvant therapy appropriately. METHODS: We studied the
      feasibility and efficacy of thoracoscopic lymph node staging (TSLN) and
      laparoscopic lymph node staging (LSLN) in esophageal cancer. RESULTS: TSLN was
      performed in 45 patients with biopsy proven carcinoma of the esophagus. LSLN was
      done in the last 19 patients. TSLN was aborted in 3 pts due to adhesions.
      Thoracic LN stage was N0 in 39 patients and N1 in 3; celiac LN were negative in
      13 and positive in 6 patients. Esophageal resection was performed in 30 patients
      after TSLN; 17 of these underwent LSLN. TSLN staging showed N0 lymph node status
      in 28 patients and N1 in 2 patients. Two of the 28 N0 patients (7%) were found at
      resection to have paraesophageal lymph node involvement (N1) and were thus
      understaged by TSLN. Thus TSLN was accurate in detecting the presence of thoracic
      LN in 28/30 cases (93%). LSLN staging found negative celiac nodes in 12 patients
      and positive LN in 5 patients. After esophagectomy, final pathology of the 12 N0
      patients was N0 in 11 and positive LN in one patient. Thus, LSLN was accurate in
      detecting lymph node metastases in 16/17 patients (94%).

PMID- 9189790
TI  - New tactile sensor techniques for localization of pulmonary nodules.
AB  - We developed a new method for thoracoscopically localizing pulmonary nodules
      using a tactile sensor. This sensor was originally designed to probe the hardness
      of an object, which is represented by changes in resonance frequency of the
      sensor (delta f: Hz). By moving over the lung surface, the sensor probe,
      introduced through a 10 mm trocar, was able to search for nodules within the
      pulmonary parenchyma thoracoscopically. When the sensor probe passed just above a
      nodule, which was harder than the adjacent tissue, a sudden sharp increase in the
      curve was observed. We have successfully utilized this method in 16 cases since
      August 1994. A representative case is that of a 68-year-old male who was admitted
      with an indeterminate nodule, demonstrated preoperatively in the left lung by
      chest computed tomography, which was localized with this technique and resected
      under thoracoscopic surgery.

PMID- 9189791
TI  - Methylene blue localizations of pulmonary nodules under CT-guidance: a new
      procedure used before thoracoscopic resections.
AB  - With the expending use of video-assisted thoracoscopy for a wide range of
      indications, we present our experience of CT-guided localizations of pulmonary
      nodules with methylene blue injections before their thoracoscopic resections.
      This technique was developed for deep non-palpable nodules of small size. Forty
      seven nodules in 44 patients were preoperatively localized under CT guidance and
      marked with methylene blue injections. The localizations under CT guidance of the
      47 nodules were successful in all cases. The surgeon confirmed accurate
      localization of 46 nodules. In one case, the injected methylene blue could not be
      identified during thoracoscopy. Complications of this technique included 7 cases
      of asymptomatic pneumothorax, 5 cases of local and asymptomatic pulmonary
      hemorrhage, and 2 cases of fits of coughing. Because of this technique, 46
      diagnostic thoracotomies could be avoided. CT guided localization with methylene
      blue injection is a simple and rapid technique enabling good thoracoscopic
      surgery results.

PMID- 9189793
TI  - A message from one of the last veterans in thoracoscopy.

PMID- 9189792
TI  - The evolution of thoracoscopic assisted surgery.

PMID- 9189794
TI  - Training in thoracoscopy in the Asia-Pacific.
AB  - Video-assisted thoracoscopic surgery should be within the armamentarium of every
      thoracic surgeon today. Rapid expansion in this field has led to an unprecedented
      demand from practising surgeons to acquire the new skills. Five levels of
      training can be described: (1) didactic lectures; (2) demonstration of
      procedures; (3) practice on simulators; (4) animal surgery; (5) preceptorship.
      The first four are usually provided in training courses or workshops, while the
      last requires proctering or attachment to a training centre. The ultimate goal is
      to integrate all these into the surgical residency programs. Developments in the
      virtual reality module may revolutionise training in the future.

PMID- 9189795
TI  - Instrumentation for video-assisted thoracic surgery.
AB  - Thoracoscopic surgery requires dedicated instrumentation which, in some way,
      differs from the usual laparoscopic instrumentation. Optics and instruments must
      be adapted to the anatomical features of the thorax. We describe the currently
      available reusable and disposable instruments as well as optical systems for
      video-assisted thoracic surgery. Future lines of development are given.

PMID- 9189796
TI  - The diverse potential of thoracoscopic assisted surgery.
AB  - Thoracoscopy has been a part of thoracic surgical practice for many years. The
      introduction of the camera chip and newer instrumentation has awakened a new
      interest in this technique and led to the development of video-assisted thoracic
      surgery (VATS). One hundred and seventy consecutive procedures performed on 158
      patients are reviewed. Video-assisted techniques have proven useful in a broad
      spectrum of thoracic surgical procedures both diagnostic (n = 90) and therapeutic
      (n = 80). Hospital mortality was 1.3%. Conversion to formal thoracotomy was
      required in 2.5%, and re-exploration for bleeding in 0.6%. The technique was safe
      and the incidence of complications acceptable. VATS was particularly helpful in
      diagnosing "indeterminate" pulmonary nodules (sensitivity of 95%), interstitial
      lung disease (histological diagnosis in all), anterior mediastinal masses and
      post transplant pneumonitis. VATS may now be the surgical treatment of choice in
      those with spontaneous pneumothorax, and it also proved useful in a variety of
      benign disorders. Its role in the management of empyaema is limited with a 57%
      conversion rate. While pulmonary resections are feasible, its role in the
      therapeutic management of malignancy is questioned. Further studies are required
      to define the precise role of VATS in thoracic surgery.

PMID- 9189797
TI  - Cost-effectiveness of thoracoscopy. The Asian perspective.

PMID- 9189798
TI  - Temporary main bronchial occlusion under bronchoscopic control in the evaluation
      of candidates for pneumonectomy.
AB  - BACKGROUND: In this study we report our experience with temporary main bronchial
      occlusion in the preoperative evaluation of candidates for pneumonectomy.
      METHODS: Between January 1991 and January 1994, 57 candidates for pneumonectomy
      underwent a 15-minute temporary main bronchial occlusion with an inflatable
      balloon during fiberoptic bronchoscopy. The following parameters were monitored
      during bronchial occlusion: general status, ECG, arterial pressure, heart rate
      and respiratory rate. Arterial blood gases were measured after 7 and 14 minutes.
      Values at 7 and at 14 minutes were compared with those obtained before the
      procedure. Patients were considered suitable surgical candidates for
      pneumonectomy if PaCO2 < 42 mmHg and pH > 7.35. RESULTS: Fifty-three patients
      were considered functionally operable. Three patients were considered
      functionally inoperable (PaCO2 > 42 mmHg, pH < 7.35 and appearance of dyspnea).
      One patient was excluded from the analysis because of balloon mispositioning due
      to a coughing fit. Sixteen of the operable patients underwent pneumonectomy and
      all did well without clinical evidence of respiratory insufficiency. At present
      11 patients are alive, all without chronic respiratory insufficiency (mean follow
      up 14 months). No postoperative mortality related to cardiorespiratory problems
      was observed. CONCLUSIONS: Temporary main bronchial occlusion is a simple and
      inexpensive test that can correctly predict functional resectability in
      candidates for pneumonectomy.

PMID- 9189799
TI  - In vitro laser nerve repair: protein solder strip irradiation or irradiation
      alone?
AB  - BACKGROUND: This study investigated the potential of sutureless nerve repair
      using two promising laser fusion methods: direct 2 microns irradiation of the
      epineurium, and protein solder assisted epineurial fusion using a 800 nm laser.
      MATERIALS AND METHODS: Laser anastomosis of the rat sciatic nerve was performed
      in vitro without stay sutures in two groups of six animals. In the first group,
      direct laser fusion used a pulsed Cr, Tm: YAG laser. In the second group an
      albumin-based fluid solder containing the dye indocyanine green was applied to
      the epineurium, then irradiated with a diode laser. These two techniques were
      compared with regards to coaptation success and axonal damage. RESULTS: Direct
      laser welding produced weak bonds despite microscopic investigation of the
      irradiated nerves showing fusion of the epineurium. The unsatisfactory bonding
      can be attributed to poor tissue overlap and insufficient protein in the thin
      epineurium denaturation of underlying axons was also observed. In contrast, the
      laser solder method produced successful welds with greatly reduced axonal damage,
      and significantly improved the tensile strength. CONCLUSIONS: This study
      confirmed the technical possibilities of sutureless nerve anastomosis. Laser
      activated solders enable stronger bonds, by the addition of protein to the
      anastomosis site, and less thermal damage to underlying tissue through selective
      absorption of laser energy by dye in the solder. Further in vivo studies are
      required before drawing final conclusions.

PMID- 9189800
TI  - Closure of the abdomen by mesh for planned re-laparotomy. A technical
      modification.
AB  - Temporary closure of the abdomen with a synthetic mesh and multiple planned
      relaparotomies are the essentials of the modern strategy for treating severe
      intra-abdominal sepsis or pancreatic necrosis. One of the complications
      associated with mesh closure of the abdomen is facial necrosis at the wound edges
      leading to evisceration. Tension of the strictures between mesh and facia called
      local ischemia, which combined with infection leads to the facial disintegration
      and separation of the mesh from the abdominal wall. A modified technique of
      suturing the mesh was developed in our department and its technical details are
      presented. Twenty-four patients treated with the "open abdominal technique and
      planned relaparotomies" are presented. The new technique was used in 9 patients
      for closure of evisceration after mesh separation.

PMID- 9189801
TI  - The use of intraoperative ultrasonography for detecting tumor extension in bile
      duct carcinoma.
AB  - The purpose of this study was to investigate the clinical feasibility of using
      intraoperative ultrasonography (IOUS) to detect tumor extension in bile duct
      carcinoma, especially longitudinal invasion along the bile ducts into either the
      hepatic parenchyma or adjacent hilar vessels. MATERIALS AND METHODS: The medical
      records of 14 patients with bile duct carcinoma who underwent surgical treatment
      at the First Department of Surgery, University of the Ryukyus, were
      retrospectively analyzed. All patients were examined by IOUS during the
      operation. The resected specimens were processed in order to compare the
      ultrasound images with the histological findings. RESULTS: The echo level of the
      primary lesion was not consistent. Specific echo patterns, such as a thickening
      of the echogenic layer (TEL) adjacent to the main tumor showing cancerous
      invasion, were observed in ten patients, 71.4% (nodular invasive 7, invasive 3)
      which were later confirmed by microscopic examinations and ultrasonic findings.
      The detection rate of TEL was 87.5% in nodular invasive type and 100% in invasive
      type, respectively. The TEL histologically coincided with a layer of fibrotic
      hypertrophy around the infiltrating tumor cells. The intramural invasion beyond
      the edge of TEL was detected in only 2 out of 11 patients. The accurate detection
      rate of the involvement of the portal vein and the hepatic artery by IOUS was
      83.3% and 60%, respectively. Based on the above findings, IOUS is thus considered
      to be essential for evaluating tumor extension along the bile ducts, and also
      greatly helps in selection of the most appropriate operative procedure,
      especially in hilar cholangiocarcinoma.

PMID- 9189802
TI  - Role of steroid in childhood haemangioma: a 10 years review.
AB  - 1195 cases of various type of haemangioma were treated with various steroid
      modalities. The response to intralesional steroids was excellent in strawberry
      and mixed haemangiomas. The response to oral steroids was also good in these two
      types. The response of cavernous variety was poor with either modality used alone
      but with combined modality, a moderate response can be obtained.

PMID- 9189804
TI  - Delayed cervical anastomosis of the esophagus for esophageal carcinoma.
AB  - BACKGROUND: The surgical approach for patients with advanced epidermoid
      esophageal carcinoma should provide an effective palliative effect with morbidity
      ratio as low as possible. Anastomotic leakage is a frequent complication and may
      be responsible for both early and late morbidity and, therefore, we assessed the
      role of delayed cervical esophagovisceral anastomosis technique in relation to
      the incidence of anastomotic complications. METHODS: Eight patients (Group 1) and
      12 patients (Group 2) submitted to one-stage or two-stage operation,
      respectively, were selected by an intraoperative assessment by the surgeon,
      considering mainly tissue blood flow of the replacement organ after its placement
      in the cervical region. RESULTS: In Group 1 anastomotic dehiscence was observed
      in 37.5% of patients, while in Group 2 no cases of dehiscence occurred (p =
      0.049). However, the postoperative mortality rate did not differ between the two
      groups (12.5% versus 0%, NS). CONCLUSION: When organ viability is uncertain,
      esophagovisceral anastomosis is best done by two-stage operation, since it
      decreases the incidence of anastomotic leak.

PMID- 9189803
TI  - Percutaneous large core needle biopsy versus surgical biopsy in the diagnosis of
      breast lesions.
AB  - OBJECTIVE: To value LCNB accuracy in the determination of morphobiological
      parameters and as an alternative to the open SB diagnostic procedure of breast
      lesions. SETTING: University Hospital, Italy. SUBJECTS: From May 1992 to February
      1995 196 biopsies have been performed. The diameter of the neoplasms examined
      varied from 0.6 to 7 cm with an average of 1.9 cm. MAIN OUTCOME MEASURES: The
      accuracy of the two methods in the evaluation of histological degree, receptor
      state, protein c-erb B2 and p53 were compared. RESULTS: No inadequate sampling
      were ever recorded. LCNB has shown values of 97% sensitivity and 100%
      specificity. The positivity and negativity predicted values obtained were 100%
      and 89% respectively. Retrospectively 70 sample-cases of carcinoma were selected
      and the morphobiological parameters evaluated. The correlation coefficients for
      the data obtained with SB and LCNB in the evaluation of Progesteron and Oestrogen
      receptor expression, protein c-erb B2 and p53 were excellent. Furthermore it was
      noted that LCNB allows a saving of at least 1/3 of the cost vs intraoperative SB.
      CONCLUSIONS: Percutaneous LCNB has high diagnostic accuracy for histological
      classification. LCNB has the same accuracy as SB for morphobiological parameters.
      The cost of LCNB is markedly lower than SB.

PMID- 9189805
TI  - Groin lymphorrhea postoperative nuisance.
AB  - Lymphorrhea is defined as the flow of lymph from disrupted lymphatic channels
      that drains externally or is contained within a wound. It complicates
      approximately 2% of vascular incisions in the groin. Of 116 patients who
      underwent different arterial reconstructions involving 186 groin wounds,
      lymphorrhea developed in 4 patients (3.4%) including 4 groins (2.1%). They have
      been managed in the Division of Vascular Surgery at King Khalid University
      Hospital (KKUH) in Riyadh, during a 3-year period ending in February 1996. There
      were 105 (90.5%) males and 11 (9.5%) females. The ages ranged from 32 to 96 years
      with a mean age of 63 years. All the 4 cases complicated with lymphorrhea were
      managed conservatively for a period of three to five weeks. In 2 cases, the
      lymphatic leak stopped and the patients discharged without other local
      complications. In the other 2 cases, lymphatic leakage stopped immediately and
      permanently following direct surgical ligation. The use of isosulphane blue for
      localization of the site of the lymphatic leak was a simple, reliable and
      accurate method during wound exploration. Follow-up of all cases for 6 months
      showed no recurrence, no sepsis and patent vascular graft.

PMID- 9189806
TI  - Complications of thyroid surgery.
AB  - The current study reports complications from thyroidectomy in 253 consecutive
      patients from 1988 to 1992. There were 10 temporary cases of hypoparathyroidism.
      After total thyroidectomy, one of 34 patients (3.2%) developed permanent
      hypoparathyroidism. Complications of recurrent laryngeal nerve (RLN) injury or
      hypoparathyroidism were no more common following completion thyroidectomy than
      total thyroidectomy. Unplanned RLN injury was seen in 13 patients of which 7 were
      permanent (2.1% of 334 nerves at risk). All 13 patients with RLN injury
      experienced a reduction in speech "loudness", but only 3 reported "hoarseness".
      The RLN may be injured without serious vocal disability. Eleven of 171 right
      RLN's at risk were injured as compared to 2 of 163 left RLN's. The volume of
      thyroid tissue resected was positively associated with RLN injury (p < 0.05) and
      not hypoparathyroidism. These findings are discussed. Hypoparathyroidism, not
      "symptomatic" RLN injury, is the most problematic complication impacting on the
      decision whether or not to perform total or completion thyroidectomy.

PMID- 9189807
TI  - Pelvic recurrence following resection of rectal cancer: a multivariate predictive
      model.
AB  - Local recurrence of rectal cancer (LR) after "curative" surgery is a major
      clinical problem, with a low resectability rate and a dismal prognosis.
      Prediction of LR might permit more targeted postoperative surveillance with
      earlier diagnosis of recurrent disease and might help in selecting the patients
      to be assigned to the most suitable adjuvant treatment protocol. To evaluate if a
      simple multivariate model could predict the LR and survival probability in the
      single case, we retrospectively evaluated 118 consecutive patients (63 males, 55
      females; mean age 62 +/- 12 years) operated on for rectal cancer and followed up
      for a minimum of 4 years (range 51-111 months). Local recurrence rate was 28%,
      with a 6% of local + distant failure. Age and sex of patients, type of surgery,
      location of tumour in the rectum, size, morphology and grading of the tumour were
      all unrelated to the event under investigation. At Cox regression, the Dukes'
      stage and the postoperative radiotherapy were the only independent prognostic
      factors for LR (p < 0.001). The multivariate model was able to correctly
      reclassify the patients and predict local recurrence in 86.2% of the cases.
      Prevention of LR by adequate surgery and adjuvant therapy as well as its early
      detection offer the best prospect of improving the results of surgery for rectal
      cancer.

PMID- 9189808
TI  - Enteral patch repair of the vena caval defect: an experimental study.
AB  - Three adult mongrel dogs were aseptically prepared and celiotomy performed under
      general anesthesia. The inferior vena cava below the renal veins was dissected
      and a 5.0 cm segment of the vena cava was clamped with Satinsky vena cava clamp.
      A segment of the anterior wall, 7.0 x 14.0 mm, of the vena cava was resected and
      the defect was sutured to the serosa of the adjacent small bowel wall with 3-0 or
      4-0 Dexon running sutures. The dogs were kept alive for 4 to 6 weeks
      postoperatively and the animals were reexplored and the vena cavogram was taken
      through a catheter in the common iliac vein using 60 per cent Urograffin. All
      three dogs were confirmed to have patent vena cava and the en-bloc segment of the
      vena cava and the small bowel was removed for the pathological specimen. The
      histological section of the specimen revealed a newly formed intimal layer
      covering the surface of the small bowel serosa patching the vena caval defect and
      this intimal layer was covered by a single layer of endothelial cells on the
      surface. With this result, the possibility of maintaining the full function of
      the vena cava following the repair of its defect with the enteral patch is
      confirmed. We do not have any clinical cases to be presented at this time, but
      this method may well be one of the applicable ways of repairing vena caval
      defects, although it may not be the best one.

PMID- 9189809
TI  - Hepatocellular carcinoma of the intrabiliary growth type.
AB  - BACKGROUND: To determine the optimal surgical therapy for patients with the
      intrabiliary growth type of hepatocellular carcinoma (HCC). METHODS: We evaluated
      257 patients with HCC who underwent liver resection from 1981 to 1990 in Kyushu
      University Hospital. RESULTS: There were 13 (5.1 per cent) with the intrabiliary
      growth type of HCC. Total bilirubin and r-glutamyl transpeptidase levels were
      higher (p < 0.05), and diameter of these tumors was larger in patients with
      intrabiliary growth type of HCC (p < 0.05). There were significant correlations
      between patients with the intrabiliary growth type of HCC and intrahepatic
      metastasis (p < 0.01), and portal vein infiltration (p < 0.01). Survival time of
      patients with the intrabiliary growth type was significantly shorter than that in
      the control group (p < 0.05). Nevertheless, two of three patients with the
      intrabiliary growth type of HCC who underwent resection of more than a 10 mm
      surgical margin survived for 5 years, respectively. CONCLUSIONS: A large number
      of patients with the intrabiliary growth type of HCC were advanced HCCs with
      intrahepatic metastasis or portal vein infiltration. However, we favour the view
      that patients have had a better prognosis if hepatectomy of more than a 10 mm
      surgical margin had been done.

PMID- 9189810
TI  - Rupture of thoracic aorta resulting from blunt trauma.
AB  - BACKGROUND: Traumatic rupture of thoracic aorta caused by blunt trauma has been
      observed more frequently in recent years. The aim of this study was to evaluate
      the state of the art of diagnostic methods used to identify this injury and the
      surgical techniques used to repair it. METHODS: The study was performed in 29
      patients undergoing surgery for traumatic rupture of thoracic aorta from November
      1979 to July 1995. RESULTS: All patients presented multiple blunt traumatic
      injuries. The suspicion of traumatic aortic rupture always arose when evidence of
      an enlarged mediastinal shadow was found on the chest X-ray, subsequently
      confirmed in 27 cases using aortography. During the period 1993-1995 11 patients
      underwent CT scan before aortography, which resulted false negative in 3 cases
      (27.2%). The decision to perform surgery was based on well defined priorities:
      abdominal injuries took priority over the aortic injury, and in stable patients
      with intracerebral injuries, head CT scan and neurosurgery were performed first.
      Eight patients died (overall mortality was 27.5%). CONCLUSIONS: CT scan should
      not be used for the diagnosis of aortic traumatic rupture because it is a waste
      of time (all patients have to undergo aortography before surgery) and the false
      negative rate is too high.

PMID- 9189811
TI  - Parathyroidectomy in the treatment of secondary hyperparathyroidism in chronic
      renal failure.
AB  - During the period 1983-1995, 200 chronic renal failure patients (115 males and 85
      females) were parathyroidectomized for hyperparathyroidism in our Department. In
      all of them, the presenting clinical symptoms, physical signs, biochemical and
      radiological tests were typically those of hyperparathyroidism. One hundred
      ninety patients were operated for the first time whereas 10 were re-operated due
      to relapse of the disease; 3 of these cases were primary hyperparathyroidism, 182
      secondary and 5 tertiary. All three primary hyperparathyroidism cases underwent
      removal of the adenoma; in the group of secondary hyperparathyroidism, 50
      underwent removal of all the parathyroid glands found, 25 underwent total
      parathyroidectomy with forearm or deltoid autograft and 60 subtotal
      parathyroidectomy whereas in 39 and 8 patients only 3 and 2 parathyroid glands
      were found respectively. In the group of tertiary hyperparathyroidism, we removed
      only the hyperplastic gland detected as the operative detection of the rest was
      not possible. Ten cases were re-operated for removal of the remaining glands. No
      complications were noted postoperatively, apart from severe hypocalcemia in 20
      cases, treated successfully by Calcium and Vitamin D administration. The highest
      relapse rate was noted among the 8 patients with only the 2 parathyroid glands
      removed. It seems that total or subtotal parathyroidectomy represents the most
      successful methods for surgical treatment of hyperparathyroidism complicating
      chronic renal failure.

PMID- 9189812
TI  - Pathologic intrathyroidal parathyroid glands.
AB  - BACKGROUND: Parathyroid glands originate from the third and fourth branchial
      pouches and migrate caudally to their final positions. Aberrations during
      migration result in anomalous locations. Intrathyroidal location is not common.
      METHODS: We reviewed cervical explorations performed from 1974 to 1993 in
      hyperparathyroidism patients. RESULTS: We found pathological intrathyroidal
      glands in six patients. Three patients had adenomas (left superior, left inferior
      and right inferior glands). The hyperplastic glands were left inferior in one
      patient and right inferior in the remaining two. Intraoperative diagnosis was
      made in three cases in which palpation of the thyroid gland showed a nodule that
      was suspected to be the parathyroid missing gland. In three patients it was a
      finding in thyroidectomy or hemithyroidectomy specimens, two of them with
      associated thyroid nodular disease. CONCLUSIONS: Ipsilateral thyroidotomy on the
      side of a palpable thyroid mass or blind hemithyroidectomy are justified if a
      presumably pathological intrathyroidal gland is suspected, when all other sites
      in the neck have been excluded.

PMID- 9189813
TI  - Effectiveness of hyperthermia and radiation treatments for patients with
      esophageal cancer predicted by the succinate dehydrogenase inhibition test.
AB  - We used in vitro succinate dehydrogenase inhibition test (SDI test) to predict
      the combined effects of hyperthermia and irradiation on specimens of esophageal
      cancer obtained at endoscopy. The mean activity of succinate dehydrogenase (SD)
      after combined treatment of 6 Gy of irradiation and 43.0 degrees C for 20 hours
      of hyperthermia was significantly decreased compared to findings with each single
      treatment (to irradiation; p < 0.01, to hyperthermia; p < 0.05). A correlation
      between the SD activity and the clinical remedial value was also examined in
      tissues from 47 patients with esophageal cancer, and treated with hyperthermia
      and irradiation, in combination. The clinical effect, determined
      radiographically, showed a correlation of 76.6%. Thus, hyperthermia plus
      irradiation is effective clinical treatment and the SDI test facilitates
      prediction of the outcome of this combined treatment.

PMID- 9189814
TI  - Effect of elastase on primary graft patency after femoralpopliteal arterial
      bypass for arteriosclerosis obliterans: a randomized, controlled study.
AB  - METHODS: Studies were carried out on 104 limbs with femoralpopliteal bypasses for
      arteriosclerosis obliterans (ASO). They were randomized to a group receiving
      elastase (10800 EL. U. P.O. per day) with an antiplatelet drug (Elastase group,
      58 patients) or a group receiving only the antiplatelet drug (Control group, 46
      patients). The follow-up period ranged from 24 to 36 months after operation at 22
      institutions across Japan. RESULTS: The cumulative graft patency rate was higher
      in the Elastase group than the Control group, but the difference lacked
      statistical significance. When autogenous saphenous veins were used, the
      cumulative graft patency rate was significantly higher in the Elastase group than
      the Control group. CONCLUSIONS: The present study suggests that elastase is
      effective in maintaining graft patency in femoralpopliteal arterial bypass when
      an autogenous saphenous vein is used as a graft.

PMID- 9189815
TI  - Pyogenic liver abscess: the role of surgical treatment.
AB  - MATERIALS AND METHODS: We present an analysis of 48 patients with pyogenic liver
      abscess (PLA) that were treated according to a protocol between 1975 and 1993. In
      this period, 35 patients with PLA were treated by surgical drainage (SD). The
      indication for surgical treatment of the abscess were patients in septic
      conditions, underlying intra-abdominal surgical disease and the
      failure/contraindication of other therapeutic methods. Thirty-one patients were
      submitted to surgical treatment as the initial procedure and four patients
      unsuccessfully treated by percutaneous drainage, underwent SD. RESULTS: The
      surgical approach was indicated in patients with severe disease and presented
      91.5% of good results, and a mortality rate of 8.5%. CONCLUSIONS: These results
      suggest that surgical treatment is a good alternative as a first step not only
      for the treatment of the primary cause of the abscess but also in septic patients
      with severe disease where a delay in adequate drainage, frequent in percutaneous
      management, can lead to high morbidity and mortality rates.

PMID- 9189816
TI  - Incidental cholecystectomy in the over-70 age group. A 19-year retrospective,
      comparative study.
AB  - OBJECTIVES: To analyse the outcome of incidental cholecystectomy in the over 70
      age-group during surgery for gastrointestinal malignancies. DESIGN: Nineteen-year
      retrospective, comparative study. SETTING: Department of Surgery B, Belinson
      Campus, Rabin Medical Center. SUBJECTS: The hospitalization records of 4,072
      patients who underwent cholecystectomy between 1975 and 1994 were reviewed. The
      incidental cholecystectomy cases for this period were identified and those
      performed during surgery for gastrointestinal malignancy were analysed
      separately. A sex- and age-matched control group was identified for comparison.
      MAIN OUTCOME MEASURES: Postoperative complications, overall morbidity and
      mortality, postoperative hospitalization days. Statistical differences in
      gallbladder-related complications and mortality among groups. RESULTS: Mortality
      and overall morbidity were significantly increased in the no-cholecystectomy
      group. Hospitalization days were increased significantly in the group not under
      going cholecystectomy and although it didn't reach statistical significance,
      there was a clear trend for increased number of pulmonary complication in this
      same group. Sepsis and multiorgan failure, as an expression of acutely,
      postoperative symptomatic gallbladder were the major cause of death in the no
      incidental-cholecystectomy group. CONCLUSIONS: Incidental cholecystectomy is safe
      and should be considered in every case of abdominal surgery, regardless of the
      age of the patient. In the over 70 age group, complication and mortality rates
      increase significantly and dreadfully when the gallbladder is left in situ after
      surgery for gastrointestinal tumors. Incidental cholecystectomy is not warranted
      in patients undergoing palliative procedures or in whom life expectancy is less
      than 6 months.

PMID- 9189817
TI  - Hernioscopy: technique and indications.
AB  - Hernioscopy is laparoscopy traversing a hernial sac used in the course of
      traditional treatment for groin hernia and it may be both diagnostic or
      therapeutic. The technique involves dissecting the hernial sac followed by
      incision, and the creation of a pouch into which a trocar is passed to permit
      laparoscopy. Once detected an abdominal lesion can also be treated
      laparoscopically: adhesiotomy, debridement, biopsy etc. The indications to this
      technique are: strangulated hernia after reduction of the intestinal loop;
      contralateral diagnosis of inguinal hernia in infants; hernias accompanied by
      abdominal pain or subocclusive syndromes. For surgeons who adopt the traditional
      approach to the treatment of groin hernias this technique represents an
      unexpected addition to their armoury.

PMID- 9189818
TI  - Right thoracotomy. Is it a safe approach in redo mitral valve replacement?

PMID- 9189819
TI  - Leukocyte-biomaterial interactions in the presence of Staphylococcus epidermidis:
      flow cytometric evaluation of leukocyte activation.
AB  - The adhesion of bacteria on a biomaterial surface is believed to be the first
      step in the development of biomaterial-related infection. The goal of this study
      was to investigate the mechanisms that permit adherent bacteria to persist on the
      surface of an implanted cardiovascular biomaterial. We hypothesized that
      circulating leukocytes are unable to adhere to the biomaterial surface under
      physiologic shear stress conditions, and this prevents them from interacting with
      adherent bacteria. To address this hypothesis, we investigated the adhesion
      profiles of Staphylococcus epidermidis and polymorphonuclear leukocytes (PMN),
      incubated under controlled shear stress conditions with the test biomaterial. We
      found that bacteria could adhere on the biomaterial surface, even when their
      concentration in the test medium was as low as 10(3) cfu/mL. At this
      concentration, the bacteria did not induce significant complement activation. PMN
      adhesion on the biomaterial surface was sensitive to shear stress and minimal at
      shear stress > 10 dynes/cm2. Low concentrations of bacteria could induce a
      significant increase in the expression of PMN adhesion molecules CD11b and CD11c.
      We conclude that the presence of bacteria induces PMN activation but does not
      increase PMN adhesion on biomaterial surfaces under physiologic shear stress
      conditions. This could be a major mechanism that protects adherent bacteria from
      PMN antibacterial activity.

PMID- 9189820
TI  - Ectopic bone induction in porous apatite-wollastonite-containing glass ceramic
      combined with bone morphogenetic protein.
AB  - To accelerate the integration of ceramic implants with the surrounding bone and
      to search for a suitable carrier for bone morphogenetic protein (BMP), we studied
      ectopic bone induction in porous apatite-wollastonite-containing glass ceramic (A
      W GC) combined with partially purified bovine BMP (bBMP) and recombinant Xenopus
      BMP-4/7 (rxBMP-4/7). Porous A-W GC rods [4 mm in diameter, 5 mm in height, 70%
      porosity, 200 microns mean pore size, 17.54 +/- 3.82 MPa (mean +/- SD)
      compressive strength] were used. An apatite coating formed on the surface of
      porous A-W GC that had been immersed in simulated body fluid at 36.5 degrees C
      for 7 days. In experiment 1, porous A-W GC rods were combined with either bBMP,
      collagen, or with both bBMP and collagen. The rods were implanted into
      subcutaneous pouches in rats and were harvested 4 weeks after implantation. Low
      energy radiographic, scanning electron microscopic (SEM), and histological
      examinations showed ectopic bone formation and within the rods only in the porous
      A-W GC combined with the bBMP and collagen group. Quantitative analysis also
      revealed that this group alone showed a significant increase in bone formation.
      In experiment 2, porous A-W GC rods were combined with rxBMP and collagen,
      implanted into rats, and harvested as described above. SEM and histological
      examination showed ectopic bone formation around and within the rods. Because of
      its relatively high mechanical strength, ease of handling, and good
      osteoinductivity, porous A-W GC combined with BMP and collagen may be clinically
      useful in patients with large cancellous bone defects or craniomaxillofacial
      lesions.

PMID- 9189821
TI  - Effects of cyclical mechanical stress on the controlled release of proteins from
      a biodegradable polymer implant.
AB  - The availability of osteogenic proteins for orthopedic applications has led to
      great interest in developing delivery systems for these substances. Standard
      release rate models are applicable in most biological settings, but orthopedic
      implants usually bear mechanical loads. To determine whether a release rate model
      for load bearing applications must consider mechanical stress, the effects of
      dynamic mechanical stress on the in vitro release kinetics of two model proteins,
      bovine albumin (BA) and trypsin inhibitor (TI), from a biodegradable film were
      evaluated. Biodegradable poly(lacticco-glycolic acid) cylindrical implants with
      embedded proteins were subjected to cyclic three point bending loading of 720
      cycles/day at 0.4 Hz for 2 weeks. Protein release into solution, swelling and
      mass loss changes, molecular weight degradation, and the presence of
      microstructural stress cracks and pores in the polymer carrier were evaluated.
      Cumulative BA and TI releases with time were significantly higher when a cyclic
      bending load was applied and increased with the magnitude of the load. Mass loss
      was not significantly greater, nor was swelling or molecular weight change of the
      polymer carrier in this 2-week interval. Pores on the surface of the polymer in
      the highest stress region were elongated into cracks, compared with pores in the
      low-stress region of the same implant, which were roughly circular. This implies
      that the pores probably act as stress risers to initiate cracks, which then
      expose more surface area, increasing protein release.

PMID- 9189822
TI  - In vitro evaluation of heparinized Cuprophan hemodialysis membranes.
AB  - Cuprophan hemodialysis membranes can be heparinized using N,N'
      carbonyldiimidazole (CDI) as a coupling agent. In this study, the characteristics
      of heparinized Cuprophan membranes have been evaluated. After immobilization,
      heparin partially retained its biologic activity. An anticoagulant activity of
      12.4 +/- 4.2 mU/cm2 was measured using a thrombin inactivation assay. Immobilized
      heparin also displayed an anti-complement activity. After contact with human
      serum; heparinized Cuprophan induced no generation of significant amounts of
      fluid phase terminal complement complex (TCC), whereas untreated Cuprophan
      induced the generation of substantial amounts of TCC. Heparinization did not
      affect the permeability of Cuprophan for model solutes with molecular weights up
      to 12,000 g/mol except for sulfobromophthalein sodium salt. The permeability of
      Cuprophan for sulfobromophthalein sodium salt was slightly decreased after
      heparinization. The ultrafiltration rate of Cuprophan increased by about 30%
      after heparinization, probably owing to an increased swelling of the membrane in
      water. Heparinized Cuprophan incubated in phosphate-buffered saline at 37 degrees
      C showed some release of heparin. These amounts of released heparin, however,
      were very low as compared to the amounts of heparin which are systemically
      administered during clinical hemodialysis treatment. It is concluded that
      Cuprophan membranes heparinized by means of the CDI-activation procedure are
      highly promising for application in hemodialyzers to be used for the treatment of
      patients with reduced or without systemic administration of heparin.

PMID- 9189823
TI  - Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior
      in human cell cultures.
AB  - Nickel-titanium alloy (Nitinol) is a metallic biomaterial that has a unique
      thermal shape memory, superelasticity, and high damping properties. Nitinol is
      potentially very useful in orthopedic surgery, for example. At present, there are
      not enough confirmative biocompatibility data available on Nitinol. The aim of
      our study was to clarify the primary cytotoxicity and corrosion rate of Nitinol
      in human cell cultures. Comparisons were made with stainless steel (Stst),
      titanium (Ti), composite material (C), and control cultures with no test discs.
      Human osteoblasts (OB) and fibroblasts (FB) were incubated for 10 days with test
      discs of equal size, 6 x 7 mm. The cultures were photographed and the cells
      counted. Samples from culture media were collected on days 2, 4, 6, and 8, and
      the analysis of metals in the media was done using flameless atomic absorption
      spectrophotometry. The proliferation of FB was 108% (Nitinol), 134% (Ti) (p <
      0.02), 107% (Stst), and 48% (C)(p < 0.0001) compared to the control cultures. The
      proliferation of OB was 101% (Nitinol), 100% (Ti), 105% (Stst), and 54% (C) (p <
      0.025) compared to the controls. Initially, Nitinol released more nickel (129-87
      micrograms/L) into the cell culture media than Stst (7 micrograms/L), but after 2
      days the concentrations were about equal (23-5 micrograms/L versus 11-1
      micrograms/L). The titanium concentrations from both Nitinol and Ti samples were
      all < 20 micrograms/L. We conclude that Nitinol has good in vitro
      biocompatibility with human osteoblasts and fibroblasts. Despite the higher
      initial nickel dissolution, Nitinol induced no toxic effects, decrease in cell
      proliferation, or inhibition on the growth of cells in contact with the metal
      surface.

PMID- 9189824
TI  - In vitro and in vivo studies of a polyester arterial prosthesis with a warp
      knitted sharkskin structure.
AB  - The present study was undertaken to assess the performance of a new knitted and
      gelatin-sealed polyester vascular graft that is believed to have greater
      dimensional stability than current commercial devices. Samples of the uncrimped,
      crimped, and sealed prosthesis were submitted to a series of in vitro and in vivo
      trials. Four commercial polyester knitted devices were included as controls for
      the in vitro tests, which included measurements of the textile and yarn structure
      and physical, chemical, and thermal properties of the graft, such as water
      permeability, dilatation, suture retention strength, melting point, and
      crystallinity index. The in vivo evaluation involved implanting the prototype
      device as a canine thoraco-abdominal bypass for periods ranging from 4 h to 1
      year and assessing the biocompatibility, biofunctionality, and biostability of
      the explanted specimens. The warp-knitted structure of the prototype device has a
      unique sharkskin stitch that confers a superior dilatation resistance and suture
      retention strength to the prosthesis. The animal trial demonstrated that the
      gelatin ensures initial hemostasis without preclotting. The gelatin is
      bioresorbed during the first 2 weeks of implantation, which generates a
      temporary, moderate, acute inflammatory response. An external capsule of
      granulomatous tissue and an internal collagen capsule are formed between the
      first and third month. Analysis of the textile and physical properties of the
      explanted prostheses confirmed there was neither dilatation nor significant
      changes in structure or mechanical performance during implantation, thus
      confirming the biostability of this new prototype device and opening the way for
      clinical trials.

PMID- 9189825
TI  - Differential healing and neovascularization of ePTFE implants in subcutaneous
      versus adipose tissue.
AB  - The preclinical evaluation of polymer biocompatibility is often performed using
      animal subcutaneous implant models. The choice of subcutaneous tissue as the
      implant site is due to a number of factors including simplicity of the surgery
      involved. Results from subcutaneous implants cannot necessarily be extrapolated
      to other tissues due to the differences in cellular composition of tissues. We
      have evaluated and compared the healing characteristics of expanded
      polytetrafluoroethylene (ePTFE) discs implanted in either subcutaneous tissue or
      epididymal fat pad tissue in rats. Following 3 and 5 weeks of implantation, the
      healing characteristics of discs were evaluated histologically with particular
      emphasis on tissue and polymer neovascularization. Implants placed in
      subcutaneous tissue exhibited limited formation of new microvascular elements
      within and directly in contact with the polymer, and the formation of an
      extensive fibrous capsule. In contrast, ePTFE implanted in the epididymal fat
      pads of rats exhibited extensive neovascularization of tissue surrounding the
      polymer, penetration of these microvascular cells into the graft interstices for
      distances < or = 100 microns and no morphological evidence of a fibrous capsule.
      The rat epididymal fat pad provides an alternative tissue for polymer healing
      evaluations. Due to the extensive presence of fat in subcutaneous tissue in
      humans, we suggest the fat pad model provides a more relevant preclinical
      evaluation of the healing characteristics of polymers used clinically in anatomic
      positions which contain significant amounts of fat.

PMID- 9189826
TI  - Identification of specific calcium-binding noncollagenous proteins associated
      with glutaraldehyde-preserved bovine pericardium in the rat subdermal model.
AB  - Calcification of glutaraldehyde-preserved bioprosthetic heart valves (BHVs)
      results in their clinical failure. The mechanism of this pathologic calcification
      is not well defined. Since serum proteins are known to be taken up in mineralized
      tissue, we hypothesized that serum proteins derived from several calcium-binding
      noncollagenous proteins (NCPs) of bone and teeth also may be associated with
      pathologically mineralized BHVs. Using a rat subdermal model of BHV
      calcification, glutaraldehyde-preserved bovine pericardium (GPBP) was implanted
      for 1, 3, 14, and 60 days, and then subjected to an extraction procedure designed
      to isolate only NCPs tightly bound to the mineral phase. Gel electrophoresis and
      Coomassie Brilliant Blue staining demonstrated that these proteins became
      associated with GPBP over time, paralleling reported calcium uptake by the
      tissue. Stains-All staining demonstrated a marked accumulation of highly acidic,
      phosphorylated NCPs associated with 60-day GPBP extracts. Some of these proteins
      were detected in rat serum but were absent from extracts of GPBP incubated in rat
      serum in vitro. Western blotting with antibodies to three NCPs found in bone and
      teeth-bone acidic glycoprotein 75 (BAG 75), osteopontin, and SPARC-demonstrated
      that these NCPs were tightly bound to the mineral phase of calcified GPBP. A
      fourth NCP, bone sialoprotein II (BSP II) was barely detectable. Thus each
      identified NCP showed a different pattern of GPBP association relative to mineral
      deposition, suggesting unique roles for each in pathologic calcification. SPARC
      increased within 3 days of GPBP implantation but decreased by 2 weeks. BAG 75 and
      osteopontin uptake was detected in the initial mineral deposits and increased
      mineralization proceeded. BSP II never increased significantly over the entire
      period. Further studies, which should include immunohistochemistry, will be
      important for delineating the source, location, and function of these three NCPs
      and for identifying others that also may be involved in this pathological
      process. Most important, the new insights into the mechanism of pathologic
      calcification described here present exciting opportunities for novel approaches
      to BHV calcification prevention.

PMID- 9189827
TI  - Studies on the desamidation of bovine collagen.
AB  - The most important reactive groups in collagen are amino, amido, guanidino, and
      carboxyl, all of which are present in comparatively large numbers. It is possible
      to modify amide groups present in the collagen of achilles tendons and hide
      trimmings by desamidation (DAM). DAM causes progressive hydrolysis of the amide
      groups of asparagine and glutamine side chains of collagen, thereby resulting in
      the reduction of the amide content of collagen. Loss of amide brings about an
      increase in the number of free carboxyl groups in the desamidated collagen, shown
      by reduction in its isoionic pH. The new modified collagen, like type I bovine
      collagen, has high viscosity and high hydroxyproline content. The fibril
      formation of the modified collagen showed slight variation, and polyacrylamide
      gel electrophoretic analysis indicated largely alpha components, indicating
      destruction of inter- and intramolecular crosslinks. The swelling behavior of the
      modified collagen is significantly higher compared to type I bovine collagen.

PMID- 9189828
TI  - Theoretical analysis of hydrolysis of polydimethylsiloxane (PDMS).
AB  - Silicones (polydimethylsiloxane, PDMS) are the materials currently used in most
      breast implants. ICP and FTIR analysis of the tissue capsule around aged breast
      implants and in vitro models show that Si-containing material is leaking from the
      PDMS implants. In this study, the hydrolysis of PDMS has been theoretically
      modeled using a semiempirical quantum mechanical method called AM1. The
      activation barrier for removing a methanol monomer was found to be +82 Kcal/mol
      while the removal of a methane monomer was +41 Kcal/mol. Using the same AM1
      method, hydrolysis of the identical to Si-O-Si identical to bond also has been
      modeled for pentasilicic acid and, in this study, for 1,1,3,3,
      fetramethyldisiloxane-1,3-diol. The barrier to the removal of a silicon
      containing tetrahedron for both studies was found to be +27 Kcal/mol. This is
      approximately one and a half times smaller than the energy of that needed to
      remove a methyl group. The pentacoordinated silicon-activated transition state
      for hydrolysis of PDMS may provide an energetically favorable pathway for
      development of a surface that will enhance chemisorption of charged protein
      molecules, and such a pathway may show up in NMR studies of the hydrolysis of
      PDMS.

PMID- 9189829
TI  - Characterization and development of RGD-peptide-modified poly(lactic acid-co
      lysine) as an interactive, resorbable biomaterial.
AB  - The design of biomaterials containing specific ligands on the surface offers the
      possibility of creating materials that can interact with and potentially control
      mammalian cell behavior. Biodegradable materials further provide the significant
      advantage that the polymer will disappear in vivo, obviating long-term negative
      tissue responses as well as the need for retrieval. In earlier studies we
      synthesized and characterized arginine-glycine-aspartic acid (RGD) peptide
      modified poly(lactic acid-co-lysine) (PLAL). In this study, both bulk properties
      and surface features have been characterized, with a focus on surface analysis as
      a means of interpreting observed changes in cell behavior. Bulk peptide
      attachments were performed using 1,1'-carbonyldiimidazole (CDI). Amino groups
      were measured using colorimetric assays and X-ray photoelectron spectroscopy
      (XPS). Peptides were measured by incorporating iodine into the peptide as a
      distinct elemental marker for use with XPS. Typical samples contained 13 +/- 4
      pmol/cm2 of amino groups and 4 +/- 0.2 pmol/ cm2 of peptides, as calculated from
      XPS measurements of nitrogen and iodine. The wettability and crystallinity of the
      samples were determined by contact angles and differential scanning calorimetry,
      respectively. Wettability and crystallinity were not altered by the incorporation
      of lysine or peptides. After incubating bovine aortic endothelial (BAE) cells for
      4 h on surfaces with RGD-containing peptides, the mean spread cell area increased
      from 77 +/- 2 microns2 to 405 +/- 29 microns2 compared to 116 +/- 11 microns2 on
      poly(lactic acid), 87 +/- 4 microns2 on PLAL, and 105 +/- 4 microns2 on surfaces
      with RDG-containing (control) peptides. The significance of this work is that the
      first synthetic interactive, resorbable biomaterial has been developed, and use
      of this material to control cell behavior has been demonstrated.

PMID- 9189830
TI  - Inhibition of smooth muscle cell growth in vitro by an antisense
      oligodeoxynucleotide released from poly(DL-lactic-co-glycolic acid)
      microparticles.
AB  - We fabricated poly(DL-lactic-co-glycolic acid) (PLGA) 50:50 microparticles loaded
      with an antisense (AS) oligodeoxy-nucleotide (ODN) against the rat tenascin mRNA
      and determined the effect in vitro of the AS-ODN released on smooth muscle cell
      (SMC) proliferation and migration. AS-ODN was entrapped using a double-emulsion
      solvent-extraction technique with high efficiency. Release of AS-ODN was
      characterized by a small initial-burst effect followed by a period of controlled
      AS-ODN release for up to 20 days. SMC proliferation studies exhibited dose
      dependent growth inhibition with AS-ODN-loaded microparticles. Microparticles
      loaded with scrambled (SC) ODN showed less growth inhibition than AS-ODN.
      Moreover, only the AS-ODN-loaded microparticles inhibited migration. These
      results demonstrate the feasibility of entrapping an AS-ODN to rat tenascin in
      PLGA microparticles for controlled delivery to inhibit SMC proliferation and
      migration.

PMID- 9189831
TI  - Factors which affect the calcification of tissue-derived bioprostheses.
AB  - Mineralization of implanted bioprostheses poses a major clinical problem.
      Crosslinking of collagenous matrices, a process used to render tissues relatively
      inert and nonbiodegradable, seems to encourage calcification. Residual,
      noncovalently bound glutaraldehyde, as well as glutaraldehyde crosslinks which
      can be degraded with time, seem to play a role in this connection. Our findings
      demonstrate the need to carefully remove noncovalently or labile-associated
      glutaraldehyde by thorough rinsing or neutralization before implantation.
      Components of a valve prosthesis such as cusps and aortic wall, which are known
      to vary in their proportions of collagen, elastin, and noncollagenous proteins
      and to calcify to different extents, can both be prevented from calcifying if
      treated with a biphosphonate before implantation. Calcification can also be
      reduced by selective enzymatic removal of noncollagenous materials. In addition
      to the age of rats, animals usually used to evaluate calcification, the strain of
      animal can markedly affect the response. The Fischer-344 rat, a highly inbred
      animal, will not calcify exhaustively rinsed implants. Our findings suggest that
      multifactorial approaches may have to be combined to generate the most ideal
      bioprostheses. These should include careful removal of noncovalently bound
      glutaraldehyde, neutralization of the nonbifunctionally reacted residues, removal
      of lipids and noncollagenous proteins (and possibly the more antigenic nonhelical
      collagen telopeptides), as well as inclusion of agents such as biphosphohates,
      which by interfering with crystal growth prevent the accumulation of mineral in
      the interstices of the tissue.

PMID- 9189832
TI  - Uterine artery Doppler velocimetry in pregnant women with lateral placentas.
AB  - The aim of this study was to compare the efficacy of placental, non-placental,
      mean of both uterine arteries Doppler velocimetry at 22-24 weeks gestation in the
      prediction of pregnancy induced hypertension (PIH) and intrauterine growth
      retardation (IUGR). Flow velocity waveforms were obtained by means of color and
      pulsed Doppler in 481 patients with lateral placentas at 22-24 weeks gestation.
      Placental location was determined by real time ultrasonography. Comparisons were
      performed between controls and pregnancies complicated by PIH and IUGR.
      Sensitivities, false positive rates and positive predictive values for PIH and
      IUGR of resistance indices (RI) above the 90th percentile, and diastolic notches
      in placental, non-placental or both uterine arteries were calculated. A mean
      uterine artery RI > or = 0.66 (90th centile) had better sensitivity than the
      placental (26.8% vs 17.1% for IUGR and 41.7% vs 33.3% for PIH) and the non
      placental uterine artery (26.8% vs 21.9% for IUGR and 41.7% vs 33.3% for PIH).
      The presence of a diastolic notch in the placental uterine artery increased
      sensitivity (31.7% for IUGR and 50.0% for PIH) and positive predictive value of
      the test. In patients with laterally implanted placentas a mean of both uterine
      arteries RI above the 90th centile and the presence of a diastolic notch in the
      placental uterine artery at 22-24 weeks have a higher predictive value for the
      subsequent development of PIH and IUGR than the separate evaluation of the 2
      uterine arteries.

PMID- 9189833
TI  - Perception of risk, choice of maternity site, and socio economic level of twin
      mothers.
AB  - The objective of this study was to determine if access to high level health
      facility (level 3 perinatal center) is related to socio-economic level of the
      mother and to her perception of risk for a twin birth. A retrospective
      questionnaire was administrated to the mothers of twins during the first post
      parum days in each of the 27 maternity sites within a defined geographical
      district near Paris (Hauts de Seine). The survey instrument was designed to
      precisely characterize the socioeconomic status of the parents, to measure the
      perceived risk for the twins expressed by the mother, to measure the relationship
      between the choice of a maternity site (level 1, 2 or 3) by socioeconomic level,
      and to measure the fetal and neonatal death rates by socioeconomic status. The
      opinion of mothers of twins about specific risk for her and for her children is
      very different by socioeconomic levels, as is the choice of level 3. This is
      discussed with the rates of fetal and neonatal death rates by socioeconomic
      level. In the absence of a policy of regionalization of perinatal care, the
      discriminant factor for access to high level care (level 3 maternity site) is the
      socioeconomic level.

PMID- 9189834
TI  - Measurement of surface tension in biological fluids by a pulsating capillary
      technique.
AB  - Ever since the discovery of the antiatelectatic function of the pulmonary
      surfactant, the measurement of surface tension (ST) has been of increasing
      importance in respiration physiology and clinical research. For the determination
      of ST, the elevation of the level of a fluid artificially pulsated in a capillary
      glass tube was monitored, and ST was calculated with the digitalized video
      computerized picture analysis program Surftens. The biological relevance of the
      method is given by the Gibbs-Thomson principle, according to which surface-active
      lipids stream towards the surface by an adsorptive process; on pulsation of the
      fluid in a capillary glass tube, therefore, ST is gradually decreased to a
      minimal value. ST values of 60 amniotic fluid samples collected from pregnancies
      with different gestation times were determined. A multiple regression analysis of
      the results, including other parameters (total protein content, total lipid
      content, phospholipid content and microviscosity), indicated that this method may
      enhance the precision of the determination of gestation time. Precision analysis
      of various samples proved that this technique gives well-reproducible results
      under the given standardized conditions. The main field of application of the
      method may be in clinical practice and in studies on as yet inadequately known
      factors affecting the ST of biological fluids.

PMID- 9189836
TI  - Estimation of gestational age by the length of the dorsal spine.
AB  - Gestational age assessed by dorsal spine length (DSL) was compared with that
      based on date of the last menstrual period (LMP). This study was performed in 70
      newborn infants admitted to a neonatal intensive care unit requiring chest
      radiography, by which dorsal spine length was measured (figure 1). Gestational
      age ranged from 23 to 42 weeks. Regression analysis were performed on DSL and
      gestational age. Estimation error was evaluated based on the percentage of
      agreement in weeks (validity) and the difference in averages between both methods
      (accuracy) (table I and figure 2). Variations during the first week of life were
      also studied and no significant differences were found. For infants born at 31
      weeks or less, DSL overestimated gestational age in one week. There was no
      differences between 32 and 36 weeks, and over 37 weeks, underestimation was one
      week (figure 3). With this correction a table was built estimating gestational
      age for different DSL; percentage of agreement was 91.4% for +/- 3 weeks (table
      III). This methodology assists the clinician to evaluate gestational age by an
      objective method, that does not vary during the first week of life and that can
      be obtained retrospectively.

PMID- 9189835
TI  - High sensitivity test for the early diagnosis of gestational hypertension and
      preeclampsia. II. Circadian blood pressure variability in health and hypertensive
      pregnant women.
AB  - The aim of this study was to describe the circadian pattern of non-invasive
      ambulatorily monitored blood pressure during the trimesters of pregnancy in
      clinically healthy women as well as in pregnant women who developed gestational
      hypertension or preeclampsia, and to compare sensitivity and specificity of
      diagnosis based on the average of the blood pressure series with the values
      obtained on the basis of casual measurements. We analyzed a total of 745 blood
      pressure series sampled by ambulatory monitoring for about 48 hours in each of
      several occasions in 189 women with uncomplicated pregnancies, 71 with
      gestational hypertension, and 29 with preeclampsia. The circadian pattern of BP
      variation for each group (complicated vs. uncomplicated pregnancies) and
      trimester of gestation was established by linear least-squares methods. Highly
      statistically different circadian patterns are demonstrated for systolic, mean
      arterial and diastolic blood pressure for both groups of pregnant women in all
      trimesters (P < 0.001 in all cases). Blood pressure decreases from the first
      trimester to the second and raises again in the third for healthy pregnant women,
      but continuously increases during gestation in women who developed gestational
      hypertension or preeclampsia. The differences in circadian rhythm-adjusted mean
      between complicated and uncomplicated pregnancies are highly statistically
      significant in all trimesters (P < .001). Sensitivity and specificity of
      diagnosing gestational hypertension based on the circadian mean are 73% and 48%,
      respectively, too low for a proper individualized diagnosis of gestational
      hypertension or preeclampsia. This study confirms the predictable circadian
      variability in blood pressure during gestation. The differences between healthy
      and complicated pregnancies can be observed as early as in the first trimester of
      pregnancy, but the use of the 24-hour mean BP does not provide a good approach
      for early diagnosis of gestational hypertension or preeclampsia.

PMID- 9189837
TI  - Hypokalaemia in pregnant women treated with the beta 2-mimetic drug fenoterol--a
      concentration and time dependent effect.
AB  - The effect of tocolytic treatment with fenoterol on plasma potassium
      concentrations was studied in 83 pregnant women on intravenous tocolytic therapy.
      Plasma concentrations of fenoterol and potassium were measured simultaneously,
      the time interval between initiation of therapy and taking the blood sample
      varying from 2 hours to 100 days. In a subset of 13 patients this blood sample
      was taken after two hours of therapy and pretreatment potassium concentrations
      were measured also. Pretreatment potassium concentrations were normal in these 13
      patients and declined to 2.88 mmol/L (median) fenoterol concentrations being 320
      ng/L through 1164 ng/L. Potassium concentrations measured later than 24 hours
      after initiation of therapy were all in the normal range corresponding fenoterol
      concentrations varying from 200 ng/L to 2504 ng/L. The multivariate statistical
      model for the description of all data showed that the duration of treatment was
      the only variable which explained the data to a significant extent. This might
      indicate that tolerance to the potassium lowering effect of fenoterol had
      developed within 24 hours after initiation of therapy. In the subset of 13
      patients pretreatment potassium concentrations were found to be more important in
      explaining potassium concentrations than fenoterol concentrations at two hours.
      As we did not observe any adverse events in patients with low potassium
      concentrations and potassium concentrations were normal within 24 hours, we
      conclude that hypokalaemia due to fenoterol in the treatment of premature labor
      is not of clinical concern.

PMID- 9189838
TI  - Ultrasonographic findings in the periventricular region in premature newborns
      with antenatal periventricular leukomalacia.
AB  - Cranial ultrasonography was carried out at least three times a week during the
      first 16 days of life in all 53 premature newborns born within study period. If a
      cyst of more than three mm was detected in the periventricular region by
      fourteenth day of life, it was judged to be antenatal PVL. Periventricular
      echodensity was classified into mild, moderate or severe periventricular
      echodensity (PVE). Among 53 newborns, 11 babies (20.8%) were diagnosed as having
      antenatal PVL. Cysts were observed in the first two days in 9 cases (81.8%) out
      of 11 babies, and in bilateral periventricular regions in 8 cases (72.7%) out of
      11 babies. All 3 babies with severe PVE in the periventricular region had PVL at
      the time of diagnosis or developed PVL shortely after severe PVE was detected.

PMID- 9189839
TI  - Male and female cord blood lipoprotein profile differences throughout the term
      period.
AB  - Age- and gender-related differences in cord serum lipids and lipoproteins were
      studied in 548 singletons from the Toledo Study, Spain, aged 37.0- < 42.0 wk,
      with body weight between 2.500 and 3.999 kg and Apgar score of > or = 7 at 1 min
      and > or = 9 at 5 min. Cord total cholesterol (TC) and LDL-cholesterol were
      significantly higher in females than in males (1.89 +/- 0.53 vs 1.72 +/- 0.42
      mmol/l, p < 0.001; and 0.88 +/- 0.43 vs 0.74 +/- 0.36 mmol/l, p < 0.001,
      respectively). With the exception of triglycerides which significantly increased
      through the term period in males and females (both p < 0.01), other serum and
      lipoprotein lipids remained rather constant between wks 38 and 42 in both sexes.
      However, all lipids and lipoproteins tended to be higher in 38 wk- than in 37 wk
      newborns. Females showed higher HDL-cholesterol levels (p < 0.05) at wk 37, and
      higher TC and LDL-cholesterol values (both p < 0.05) at wks 39 and 40. TC was
      more or less equivalently carried by LDL and HDL in both sexes but males
      transported significantly more cholesterol by VLDL (p < 0.001) and less by LDL (p
      < 0.05) than females. TC was significantly correlated with LDL-cholesterol (p <
      0.001) and HDL-cholesterol (p < 0.001). The different levels of TC and LDL
      cholesterol, and the cholesterol distribution for lipoproteins in male and female
      neonates suggest that gender-related factors might influence lipid levels at term
      period.

PMID- 9189840
TI  - Neonatal outcome in women treated for the antiphospholipid syndrome during
      pregnancy.
AB  - The aim of this study was to determine the neonatal outcome in women with well
      characterized antiphospholipid syndrome treated during pregnancy with low-dose
      aspirin. We compared 38 babies born after 36 pregnancies of 33 women diagnosed as
      having antiphospholipid syndrome with a group of 38 control infants matched for
      the same gestational age at birth. In all 76 newborns we studied the maternal
      events associated with the antiphospholipid syndrome, mothers' treatment and
      neonatal data. All mothers with antiphospholipid syndrome were treated with low
      dense aspirin. Prednisone was only prescribed due to maternal complications and
      heparin in a case of thrombosis. No significant relation was found between
      maternal treatment and neonatal complications. The prematurity rate in these
      newborns was high 14% and the neonatal mortality (5.8%) was only associated with
      extreme prematurity (p < 0.001). In our population the overall rate of neonatal
      complications was higher than in the general population, but when compared with a
      similar group of newborns no significant differences were found. Our results
      suggest that primary antiphospholipid syndrome appears to be improved by low-dose
      aspirin treatment, with a high rate of neonatal survival (95%). Except for
      prematurity and its potential associated complications, fetal and neonatal
      outcome is very favourable and no significant relation between maternal treatment
      and neonatal pathology has been detected.

PMID- 9189841
TI  - Anthropometric characteristics of full-term infants: effects of varying degrees
      of "normal" glucose metabolism.
AB  - Aim of this study was to examine the maternal-neonatal outcome and the neonatal
      anthropometric characteristics of a full-term mother-infant pairs group with a
      positive oral glucose challenge test (GCT) without gestational diabetes mellitus
      (GDM). Our study involved 1615 white women with singleton pregnancies who
      underwent universal screening for GDM in two periods of pregnancy. This
      population was divided into three groups according to GCT results: 1) 172
      patients with abnormal GCT in both periods; 2) 391 patient with normal GCT in the
      early period and abnormal GCT in the late period; 3) 1052 patients with normal
      GCT in both periods (control group). The incidence of LGA (large for gestational
      age) infants was higher in Group (40.7%) and Group 2 (22.0%) respect to control
      group (8.3%) (p < 0.00001 and p < 0.0001 respectively) and was significantly
      different in the two groups (p < 0.0008). Comparison among the three groups of
      LGA infants showed the following results: male and female newborns of Group I
      were heavier than those of Group 2 and of the control group, while males and
      females of the control group had significantly greater length and cranial
      circumference means. A significant decrease in ponderal index, choracic
      circumference, weight/length ratio means could be seen as well as a significative
      increase in cranial/thoracic circumference ratio means from Group I to the
      control group. These data confirm the involvement of fetal development in terms
      of weight and anthropometric characteristics in the presence of alterations in
      maternal glucose metabolism which are not currently classified as gestational
      diabetes.

PMID- 9189843
TI  - Microcephaly due to fetal brain disruption sequence. Case report.
AB  - A case of microcephaly that developed intrauterine is described. Since it began
      three weeks after a car accident during second trimester of pregnancy, we
      attribute it to "brain disruption sequence" resulting in an arrest of brain
      development after the injury.

PMID- 9189842
TI  - Comparison of two methods for the discrimination of avoidable perinatal deaths.
AB  - This paper analyzes the validity and reliability of a method proposed by HERMAN
      et al [8] used to classify avoidable neonatal deaths. This method is based on a
      list of amenable medical conditions with an a priori decision about the avoidance
      of deaths. The results obtained using this method are compared to those derived
      from the discussion of individual cases by a committee created ex profeso. The
      population under study includes all neonatal deaths occurred at a third level
      hospital in Mexico City, from January 1, 1987 to July 31, 1994 (n = 1337). Only
      56% of neonatal deaths could follow HERMAN's classification (n = 749). Poor
      concordance (Cohen's Kappa = 0.30) between the two methods was found. A high
      proportion of deaths (72.7%) was classified ambiguously (as possibly
      preventable), and also a considerable proportion of deaths could not be
      classified (44%). High sensitivity (96%) was found for the small percentage of
      cases in which avoidance was determined by the method under assessment (15%). A
      priori classification is useful for developing rough quality indicators at the
      regional level but not at hospital settings.

PMID- 9189844
TI  - Fetal ventricular rate in case of congenital complete heart block is increased by
      ritodrine. Case report.
AB  - We encountered a case of fetal bradycardia (57 bpm) induced by heart block. The
      continuous intravenous administration of ritodrine to a mother to treat fetal
      brady-cardia at 28 weeks of gestation successfully increased the fetal
      ventricular rate by 15 bpm (from 57 to 72 bpm). Pregnancy was continued for 10
      weeks, and fetal cardiac failure did not occur. The fetal ventricular rate
      gradually decreased to 52 bpm after discontinuation of the ritodrine infusion. It
      is suggested that maternal administration of ritodrine can be considered in a
      case of life-threatening fetal bradycardia induced by complete heart block.

PMID- 9189845
TI  - Walking a mile in their shoes... Symbolic interactionism for families living with
      severe mental illness.
AB  - 1. With deinstitutionalization and changes in legal rights of patients, care of
      patients with severe mental illness has shifted from a hospital-based to a
      community-centered system. 2. Families often serve as an extension of the mental
      health system, providing important case management functions such as assessment,
      monitoring, crisis management, and advocacy. 3. Symbolic interactionism provides
      a framework for understanding the role of meaning in individual and family
      responses to the disruption of life that results from severe mental illness.

PMID- 9189846
TI  - Seclusion and the lunar cycles.
AB  - 1. The lunar cycle's influence over psychological disturbances in the human being
      is known as the Transylvanian effect. 2. Seclusion is used predominantly for the
      control and management of violence and aggression in patients. 3. If the
      Transylvanian effect is supported, a relationship between lunar cycles and the
      use of seclusion should exist; no such correlation, however, was found in this
      study.

PMID- 9189847
TI  - Forensic nursing in Pakistan. Bridging the gap between victimized women and
      health care delivery systems.
AB  - 1. Women's issues tend to be more pronounced in developing countries, where they
      include extreme limited resources, poor communication, vast distances, individual
      and community poverty, and lack of education. 2. Empowerment of victimized women
      depends on support, information, resources, creativity, and positive self
      concept. 3. Through support, understanding, effort, and determination, the
      forensic nurse and Pakistani women can translate a vision into reality by the
      integration of victimized women into all aspects of society.

PMID- 9189848
TI  - Insight into Bedlam: one hospital's history.
AB  - Mental health services are in a state of flux. We struggle with the most basic
      concepts-can we distinguish between the need for "health" as opposed to "social"
      care? Mental distress is instantly recognizable, but less clear is what causes
      such distress or how we should respond to it. We have become so involved with
      current challenges that we assume that these are new-that we are living in a
      world beyond the end of psychiatric history. This article focuses on the Bethlem
      Hospital, 750 years old this year. An overview may help us to appreciate that our
      contemporary problems are the result of history and that the concept of care is a
      vital part of that. Nurses are trying to improve the response to the special
      needs of mothers with a mental illness. Such developments are the latest in a
      history of innovation and change. We too are part of that process and hopefully,
      our efforts will be seen as a meaningful contribution to the care of those with
      mental illness.

PMID- 9189849
TI  - Up in smoke? Linking patient assaults to a psychiatric hospital's smoking ban.
AB  - 1. During a smoking ban in a large public psychiatric hospital, pre-ban
      predictions of escalating patient management problems due to the ban did not
      materialize. 2. One element of the smoking ban's success was the support
      available for patients to channel their frustrations constructively, and for
      staff to be creative within the limits of the smoking ban policy. 3. Since the
      adoption of the smoking ban, New Hampshire Hospital has produced a smoke-free and
      healthier environment for patients, staff, and visitors.

PMID- 9189850
TI  - 'Never again'. Model mugging: a therapeutic resource for the psychiatric nurse.
AB  - I was in a room that had no windows and a disorienting effect. No light reached
      the room from outside and the fluorescent light gave the cement walls a
      forbidding appearance. The only sound was of my footsteps as they ricocheted off
      the walls, making them seem louder than ever. I felt cut off from the outside
      world. I was nervous, and my heart was beating loudly. I tried to remain calm,
      grounded, and in the present moment, but my mouth was dry, my shoulders tense,
      and my mind unable to focus. Seemingly out of nowhere I was grabbed from behind.
      Without thinking, my right arm swung up and around, glancing the side of my
      attacker's head. As I swung to the right with my arm. I pinched my fingers
      together and struck at his eyes. I flopped to the floor, laying on my left side
      with my right leg raised knee-to-nose and my arm raised to protect my head,
      waiting for him to come after me. He jumped on top of me but I kicked him in the
      head three times. He raised his hands to his forehead, signaling that I had hit
      his head hard enough with the heal of the foot to knock him unconscious. I stood
      up over him, stomped my foot, and yelled "No! 9-1-1!" Only then was I aware of
      the women behind me, cheering me on as I defended myself against an assault in
      the Model Mugging Program.

PMID- 9189851
TI  - Transcriptional regulation of aquaporin-2 water channel gene by cAMP.
AB  - Aquaporin-2 (AQP-2) water channel is a key molecule for urinary concentration
      whose expression is augmented by dehydration in vivo. To elucidate the regulatory
      mechanism of this phenomenon in vitro, mouse collecting duct cell lines were
      established from a transgenic mouse harboring temperature-sensitive simian virus
      40 large T antigen gene and then screened for the AQP-2 expression, using
      ribonuclease protection assay. In one cell line designated C4, the endogenous AQP
      2 mRNA level measured by ribonuclease protection assay increased fourfold after
      treatment with chlorophenylthio-cAMP (cpt-cAMP) (400 microM). In contrast,
      phorbol 12-myristate 13-acetate did not affect the AQP-2 mRNA level. To identify
      the molecular mechanism(s) of cAMP-induced upregulation of AQP-2 mRNA in C4
      cells, luciferase assay was performed using various 5'-flanking regions of the
      human AQP-2 gene. Luciferase activity in C4 cells transfected with constructs
      containing approximately 2.8-kbp or 224-bp 5'-flanking region showed a 3.5-fold
      increase by cpt-cAMP treatment, indicating that the 224-bp 5'-flanking region
      contains the elements necessary for cAMP-induced regulatory mechanisms. This
      region contains cAMP-responsive element (CRE), and the deletion of the core
      sequence of CRE (GACGTCA) or introduction of mutation into CRE (GTGGTCA)
      completely abolished the responsiveness to cpt-cAMP, confirming the key role of
      CRE in the cAMP-induced transcriptional activation of the AQP-2 gene.
      Electrophoretic mobility shift assay revealed the existence of proteins binding
      to CRE in C4 cells and in rat kidney. The binding of CRE proteins to CRE was
      increased in the nuclear extract from cpt-cAMP-treated C4 cells and dehydrated
      rat kidney compared with those from controls. These results demonstrated that the
      CRE in the AQP-2 gene promoter is a key cis-element for cAMP-mediated
      transcriptional regulation of this gene and may be important for in vivo
      regulation of AQP-2 expression in a dehydrated state.

PMID- 9189852
TI  - Adaptational changes in renal vacuolar H(+)-ATPase in the rat remnant kidney.
AB  - After 7/8 nephrectomy, the remnant kidney exhibits an adaptive increase in acid
      secretion per nephron. We studied the role of the kidney vacuolar H(+)-ATPase in
      this adaptational response by anti-H(+)-ATPase immunocytochemistry in kidneys
      from rats subjected to 7/8 nephrectomy or a sham procedure at 1, 2, and 3 wk
      after surgery. No changes in H(+)-ATPase staining were apparent in the proximal
      tubule, thick ascending limb, or distal convoluted tubule. In the cortical
      collecting ducts, the percentage of intercalated cells with well-polarized apical
      and well-polarized basolateral H(+)-ATPase staining was significantly higher in
      the remnant kidneys at 1, 2, and 3 wk. In the medullary intercalated cells of the
      sham-operated kidneys, relatively few cells had predominant plasma membrane H(+)
      ATPase staining. In the remnant kidneys, the percentage of medullary intercalated
      cells with predominant plasma membrane H(+)-ATPase staining was increased
      significantly at 1 and 2 wk after surgery, returning to sham-operated values at 3
      wk. The results indicate that intercalated cells in the collecting ducts of both
      cortex and medulla participate in the adaptation to reduction in renal mass by
      changing the steady-state distribution of H(+)-ATPase, similar to changes that
      occur with chronic acid administration.

PMID- 9189853
TI  - Minimum urine flow rate during water deprivation: importance of the nonurea
      versus total osmolality in the inner medulla.
AB  - Antidiuretic hormone leads to an increase in the permeability for water and urea
      in the inner medullary collecting duct. Hence, urea may not be an "effective"
      osmole in the inner medulla during maximal renal water conservation. Accordingly,
      the purpose of this study was to evaluate whether differences in the rate of urea
      excretion would influence maximum renal water conservation in humans. In water
      deprived rats, the concentration of urea and total osmolality were somewhat
      higher in the urine exiting the inner medullary collecting duct than in
      interstitial fluid obtained from the entire papillary tip. Nevertheless, the
      "nonurea" (total osmolality minus urea in millimolar terms) osmolality was
      virtually identical in both locations. Chronically fasted human subjects that
      were water-deprived for 16 h had a lower rate of urea excretion (71 +/- 7 versus
      225 +/- 14 mumol/min) and a somewhat lower urine osmolality (745 +/- 53 versus
      918 +/- 20 mosmol/kg H2O). Nevertheless, they had identical urine flow rates (0.5
      +/- 0.01 and 0.5 +/- 0.02 ml/min, respectively), and their nonurea osmolality
      also was similar (587 +/- 25 and 475 +/- 14 mosmol/kg H2O, respectively) to the
      water-deprived normal subjects. The composition of their urine differed in that
      the principal nonurea osmoles became NH4+ and beta-hydroxybutyrate rather than Na
      and C1. During water deprivation in normal subjects, the ingestion of urea caused
      a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise
      in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine,
      and presumably the medullary interstitial fluid as well, was inversely related to
      the urea excretion rate. In chronic fasting, the nature, but not the quantity, of
      nonurea osmoles changed. The similar minimum urine volume was predictable from an
      analysis based on nonurea osmole considerations.

PMID- 9189855
TI  - Glomerular hyperfiltration during sympathetic nervous system activation in early
      essential hypertension.
AB  - Glomerular hyperfiltration may be important for the development of essential
      hypertension. Both the renin-angiotensin system and the sympathetic nervous
      system influence renal hemodynamic regulation. To test the hypothesis that
      glomerular hyperfiltration can be unmasked by sympathetic nervous system
      activation, renal hemodynamics and humoral components of the renin-angiotensin
      system were examined at rest and during mental stress in 45 young normotensive
      healthy subjects and 37 young people with mild essential hypertension. GFR and
      renal plasma flow (RPF) were determined with inulin and para-aminohippuric acid
      clearance at rest and during stress. At rest, RPF, GFR, filtration fraction,
      plasma renin activity, angiotensin (Ang) II concentrations, and serum aldosterone
      values were similar in normotensive and hypertensive subjects. After stress,
      blood pressure increased (P < 0.01), but this was nearly identical in
      normotensive and hypertensive subjects (7.05 +/- 6.9 versus 7.03 +/- 4.6 mmHg,
      NS). The decrease in RPF (-27 +/- 54 versus -22 +/- 25 ml/min per 1.73 m2, NS)
      was also similar in the two groups. In contrast, the increase in GFR (+ 10.5 +/-
      7.2 versus 6.08 +/- 5.7 ml/min per 1.73 m2, P < 0.001) and filtration fraction
      (+2.48 +/- 1.38 versus 1.82 +/- 1.49%, P < 0.05) was more marked in hypertensive
      than in normotensive subjects. The concomitant increase in Ang II concentrations
      was greater in hypertensive than in normotensive subjects (+4.6 +/- 1.0 versus 
      1.0 +/- 0.45 pg/ml, P < 0.001). The increase in GFR during mental stress was
      correlated with the increment in Ang II concentrations (r = 0.39, P < 0.001).
      Compared with the placebo control phase, blockade of the renin-angiotensin system
      with an angiotensin-converting enzyme inhibitor attenuated the increase in GFR
      during stress in hypertensive (8.04 +/- 5.01 versus 10.1 +/- 5.7 ml/min per 1.73
      m2, P < 0.05), but not in normotensive, subjects. Even in early essential
      hypertension, glomerular hyperfiltration is evident during sympathetic nervous
      system activation, which is mediated by postglomerular vasoconstriction. This
      early stress-induced glomerular hyperfiltration may contribute to, or trigger,
      the development of essential hypertension.

PMID- 9189854
TI  - Renal nerves do not mediate vasoconstrictor responses to acute nitric oxide
      synthesis inhibition in conscious rats.
AB  - Nitric oxide is a physiologically important peripheral and renal vasodilator. The
      studies presented here were conducted in the conscious, chronically catheterized,
      unstressed rat to investigate whether NO interacts with renal efferent
      sympathetic nerve activity in control of blood pressure, renal vascular
      resistance, and sodium excretion. Renal clearance studies were conducted in
      normal rats with innervated kidneys and in a separate group of rats with chronic,
      bilateral renal denervation. Acute systemic inhibition of NO synthesis with n
      nitro L-arginine methyl ester (L-NAME) leads to hypertension, renal
      vasoconstriction, and natriuresis in rats with intact renal nerves. Chronic renal
      denervation does not diminish the pressor and renal vasoconstrictor response to
      NO synthesis inhibition, although the natriuretic response is prevented.
      Stimulation of renal NO synthesis with the substrate L-arginine produces
      selective renal vasodilation and a marked osmotic diuresis in the innervated
      kidney. Renal denervation has little impact on the responses to L-arginine. These
      studies suggest that in the normal, conscious, chronically catheterized rat in
      which the sympathetic nervous system is operating at basal levels, renal nerve
      activity does not contribute to the pressor or renal vasoconstrictor response to
      NO inhibition or the renal vasodilator response to NO stimulation. These
      observations contrast with earlier observations made under conditions of stress
      induced activation of renal nerve activity.

PMID- 9189856
TI  - Erythropoietin-induced hypertension in rat is not mediated by alterations of
      plasma endothelin, vasopressin, or atrial natriuretic peptide levels.
AB  - Regular administration of recombinant erythropoietin (EPO) in patients with
      chronic renal failure (CRF) is frequently complicated by a rise in arterial blood
      pressure. Clinical studies intended to discern the possible role of endothelin
      (ET) in the pathogenesis of EPO-induced hypertension have produced contradictory
      results. Given the limitations of the clinical studies, this placebo-controlled
      study was carried out in CRF (5/6 nephrectomized) rats treated with either EPO,
      150 U/kg intraperitoneally, or the vehicle alone twice weekly for 6 wk. Plasma ET
      was measured at baseline, and weeks 2, 4, and 6. In addition, plasma arginine
      vasopressin (AVP) and atrial natriuretic peptide (ANP) were determined at the
      conclusion of the study period. As expected, blood pressure rose markedly after 1
      wk of EPO therapy as compared with the placebo therapy. However, there was no
      significant difference in plasma ET levels between the EPO- and placebo-treated
      groups during the study period. Likewise, EPO therapy had no effect on plasma ANP
      level but depressed plasma AVP concentration. Thus, this placebo-controlled
      animal study revealed that EPO therapy markedly raised arterial blood pressure
      but had no effect on plasma ET in the CRF rats. This observation suggests that
      EPO-induced hypertension in this model is not mediated by an increased
      circulating ET level. However, the possible effect, if any, of EPO on local
      vascular tissue ET level is uncertain and awaits further investigation.

PMID- 9189857
TI  - Thrombin increases clusterin mRNA in glomerular epithelial and mesangial cells.
AB  - Clusterin, a multifunctional protein with complement blocking activity, and
      fibrin, a product of thrombin's enzymatic activity, are present in the kidney
      during acute and chronic renal failure. The role of thrombin in regulating
      clusterin mRNA in the kidney is not known. The effect of thrombin on clusterin
      mRNA expression was examined in rat glomerular mesangial and glomerular
      epithelial cells, and cultured human renal proximal tubular epithelial cells by
      northern blot. Thrombin (10(-8) M) increased clusterin mRNA levels two- to
      fourfold in glomerular mesangial, glomerular epithelial, and proximal tubule
      epithelial cells. This was a specific effect of thrombin receptor activation
      because peptides corresponding to the tethered ligand of the thrombin receptor
      were also able to increase clusterin mRNA levels. Epidermal growth factor,
      insulin-like growth factor-1, and transforming growth factor-beta 1 had little or
      no effect on clusterin mRNA levels. The protein kinase C inhibitor RO-32-0432 (1
      microM) inhibited the thrombin-induced increase in clusterin mRNA, suggesting
      that thrombin receptor activation may regulate renal clusterin mRNA levels
      through protein kinase C.

PMID- 9189858
TI  - Evidence for involvement of IgA1 hinge glycopeptide in the IgA1-IgA1 interaction
      in IgA nephropathy.
AB  - The study was performed to investigate the role of the IgA1 hinge region in the
      IgA1-IgA1 interaction, which was observed previously in IgA nephropathy. The
      competitive inhibition assays of the IgA1-IgA1 binding were performed using the
      following candidates for inhibitors: native IgA1 hinge glycopeptide (nHGP), IgA1,
      IgA2, and IgG. The IgA1-IgA1 binding was definitely inhibited by the nHGP and the
      IgA1 (maximum of percent inhibition: 66.1 and 60.5%, respectively). There was no
      obvious inhibition in the IgA2 and the IgG. The inhibition curves of the nHGP and
      the IgA1 were significantly different from that of the IgG (P < 0.01,
      respectively). Furthermore, to reveal the detailed binding sites in the
      interaction, the same inhibition assays were performed using the following
      substances composing the IgA1 hinge glycopeptide: galactose (Gal), N-acetyl
      galactosamine (GalNAc), Gal beta 1-3GalNAc, sialic acid, tetrapeptide PTPS, and
      synthesized hinge proline-rich peptide PVPSTPPTPSPSTPPTPSPS (sHP). sHP, Gal beta
      1-3GalNAc, Gal, and GalNAc inhibited the binding (69.3, 34.1, 14.9, 14.6%,
      respectively). No obvious inhibition was observed in sialic acid and tetrapeptide
      PTPS. The inhibition curve of sHP was significantly different from that of the
      PTPS (P < 0.05). Those of Gal beta 1-3GalNAc, Gal, and GalNAc were also
      significantly different from that of sialic acid (P < 0.05, respectively). These
      results suggested that the IgA1-IgA1 interaction could be mediated by the core
      structure including the peptide and the sugars, except for sialic acid in the
      hinge region, resulting in the formation of the circulating macromolecular IgA1
      in IgA nephropathy.

PMID- 9189860
TI  - Impaired Na(+)-H+ exchanger activity of hepatocytes in chronic renal failure.
AB  - Available data indicate that cation transport is impaired in many cells in
      chronic renal failure (CRF). The information on the activity of the Na(+)-H+
      exchanger in CRF is variable, and both increased and reduced activity have been
      reported. The mechanisms through which CRF may exert an effect on the Na(+)-H+
      transport are not known. Data exist indicating that PTH inhibits the Na(+)-H+
      exchange in kidney and liver, and this action of hormone is most likely due to
      its ability to raise cytosolic calcium ([Ca2+]i). Therefore, it is possible that
      excess PTH in CRF may adversely affect the activity of the Na(+)-H+ antiport.
      This study examines the activity of Na(+)-H+ antiport, intracellular pH (pHi),
      and buffering capacity of hepatocytes obtained from rats after 6 wk of CRF, from
      CRF parathyroidectomized animals, and from CRF rats and normal rats treated with
      verapamil. The pHi and the buffering capacity of hepatocytes were not different
      in all groups of animals. The activity of the Na(+)-H+ antiport of hepatocytes
      from CRF animals was significantly (P < 0.01) lower than in hepatocytes from
      normal rats, CRF parathyroidectomized rats, CRF rats treated with verapamil, and
      normal rats treated with verapamil, and the values in the latter four groups of
      animals were not different. This impaired activity of Na(+)-H+ antiport in CRF
      was observed in all external concentrations of sodium (25, 50, 75, 100, 125, and
      150 mM). Thus, CRF altered the kinetics of the transporter in that its Vmax
      decreased and its K(m) increased. The data show that: (1) CRF is associated with
      reduction in the activity of Na(+)-H+ antiport in hepatocytes; (2) this defect is
      due to the state of secondary hyperparathyroidism of CRF; and (3) excess PTH
      mediates its effect by elevating [Ca2+]i of hepatocytes because treatment of CRF
      animals with verapamil, which blocks the PTH-induced rise in [Ca2+]i of these
      cells, prevented the impairment in the activity of the Na(+)-H+ antiport.

PMID- 9189861
TI  - P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes.
AB  - In the end-stage renal disease patient, certain uremic compounds could influence
      the cellular accumulation of aluminum (Al). In this study, we examined the effect
      of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity
      of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken
      up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased
      cellular Al uptake and aspartate aminotransferase release and decreased cell
      growth when Tf-Al, not Al citrate, was added to culture media. Compounds that
      have been extracted previously from these ultrafiltrate fractions (p-cresol,
      xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested
      for their effect on Al uptake and toxicity in MH at concentrations found in
      uremic serum. Significant Al uptake by MH was observed only when p-cresol was
      added together with Tf-Al. Time-response curves showed increased Al uptake and
      toxicity at p-cresol concentrations of 3 mg/dl in culture media. Dose-response
      curves confirmed that Al uptake and cell toxicity were proportional to p-cresol
      from 1.5 mg/dl to 3 mg/dl in culture media. p-Cresol was not toxic to MH in the
      absence of Tf-Al in media. p-Cresol increased Tf-associated Al uptake only
      because there was no effect on Al uptake when Al citrate was substituted, and
      studies with Tf-I125-Al in the presence of this compound showed increased Tf-I125
      taken up by MH. p-Cresol did not increase Tf saturation with Al. p-Cresol also
      increased Tf-Al uptake in Friend erythroleukemia and neuroblastoma cells in
      culture. Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14,
      and 15 increase the uptake and toxicity of Al in cultured MH. These compounds may
      play a role in the accumulation and toxicity of Al in the liver of end-stage
      renal disease patients and possibly in all cells that express Tf receptors.

PMID- 9189859
TI  - Role of bradykinin B2 receptors in neonatal kidney growth.
AB  - The kallikrein-kinin system is developmentally expressed in newborn kidneys. In
      addition, bradykinin (BK) is mitogenic in cultured glomerular mesangial cells.
      However, the role of endogenous BK in postnatal renal development has not been
      defined. In this study, the role of the BK-B2 receptor in neonatal kidney growth
      in the rat was examined. RNA blot analysis and semiquantitative reverse
      transcription-polymerase chain reaction showed that BK-B2 mRNA levels were
      approximately 30- to 40-fold higher in newborn than adult kidneys. Treatment of
      newborn rats with the selective BK-B2 antagonist, Hoe 140 (600 micrograms/kg per
      day, sc), from days 1 through 14 of life significantly reduced body weight,
      kidney-to-body weight ratios, and kidney DNA content, compared with saline
      treated controls. Hoe 140 treatment had no effect on kidney protein or RNA
      content or the expression of transforming growth factor-beta mRNA. The growth
      retardation induced by BK-B2 blockade was observed only in the kidney and, to a
      lesser extent, in the heart. BK-B2 blockade had no effect on renal growth in
      adult rats, suggesting that these effects are developmentally regulated. In
      contrast to Hoe 140 treatment, neonatal protein undernutrition resulted in a
      generalized reduction in kidney DNA, RNA, and protein contents; increased renal
      transforming growth factor-beta gene expression; and decreased renal kallikrein
      expression and enzymatic activity. The results suggest that activation of BK-B2
      receptor expression in the neonatal kidney plays an important role in the
      regulation of DNA synthesis during the latter stages of nephrogenesis.

PMID- 9189862
TI  - Overexpression of GLUT2 gene in renal proximal tubules of diabetic Zucker rats.
AB  - Renal tubular reabsorption of glucose is substantially increased in humans and
      rats with diabetes mellitus. The influx of luminal glucose is mediated by
      Na+/glucose cotransporter system and glucose efflux from tubules to interstitium
      by facilitative glucose transporters (GLUT). In Zucker diabetic rats, GLUT2
      protein levels of renal proximal tubules were higher than in control litter
      mates: 9.67 +/- 1.95 versus 4.72 +/- 1.55 (P = 0.0073). In the same proximal
      tubules, diabetes was associated with minor decreases in GLUT1 protein levels:
      1.96 +/- 0.37 for diabetics and 2.37 +/- 0.34 for controls (P = 0.12).
      Na+/glucose cotransporter system protein levels were similar in both groups,
      whereas Na+/K+ ATPase levels were slightly decreased in diabetic rats, but the
      difference was not statistically significant. In this report, it is suggested
      that in long-term uncontrolled diabetes, GLUT2 transporters are overexpressed in
      renal tubules. This adaptation promotes low-affinity, high-capacity glucose
      efflux. The higher number of high K(m) GLUT2 ensures that glucose reabsorption is
      increased by promoting glucose efflux, which could be rate-limiting in the face
      of hyperglycemia.

PMID- 9189863
TI  - Critical role of the extracorporeal blood temperature in the hemodynamic response
      during hemofiltration.
AB  - Impaired vascular reactivity during combined ultrafiltration-hemodialysis (UF+HD)
      compared with hemofiltration (HF) remains a rather enigmatic problem, the causes
      of which are still not well understood. Although a number of factors have been
      claimed to be responsible, most recent studies point to a major role of the
      extracorporeal blood temperature, which is usually lower during HF compared with
      UF + HD. However, previous studies in which hemodynamics were studied during UF +
      HD and HF in relation to the extracorporeal blood temperature are limited by the
      use of acetate in UF + HD, and measurements were often confined to BP and heart
      rate. Therefore, arterial BP, as well as forearm vascular resistance (FVR) and
      venous tone (strain-gauge plethysmography), was measured in 11 hemodialysis
      patients during 3 h UF + HD (37.5 degrees C) and predilution HF (39.0 degrees C =
      warm HF), resulting in equivalent extracorporeal blood temperatures. Patients
      were also studied during cold HF at an infusate temperature of 36.0 degrees C. UF
      + HD and HF were matched with respect to the dialysate and infusate composition
      (bicarbonate), bio-compatibility factors, and small molecule clearance. At
      equivalent temperatures, UF + HD and HF were associated with a comparable
      vascular and BP response. Only cold HF was associated with a significant increase
      in FVR. In addition, FVR and venous tone, as well as arterial BP, were all
      significantly higher during cold HF compared with both UF + HD and warm HF. These
      results indicate that the disparity in vascular reactivity between UF + HD and HF
      is primarily related to differences in the extracorporeal blood temperature.

PMID- 9189864
TI  - Effect of controlled extracorporeal blood cooling on ultrafiltration-induced
      blood volume changes during hemodialysis.
AB  - Considerable amounts of heat may be lost or gained through the extracorporeal
      circuit during hemodialysis and influence the hemodynamic stability of the
      dialysis patient. The effects of two levels of extracorporeal heat flux (Jtherm
      in W) on blood pressures and ultrafiltration-induced blood volume changes were
      studied in eight patients on conventional hemodialysis. Treatments were
      controlled automatically for mild to medium Jtherm of either -13.4 +/- 3.3 W
      (group A) or -30.2 +/- 3.7 W (group B) (1 W = 1 J/s = 3.6 kJ/h = 0.239 cal/s =
      0.86 kcal/h) and repeated once. Values are given as mean +/- SD. With low blood
      flows (Qb = 251 +/- 21 ml/min), dialysate temperatures were automatically set at
      37.3 +/- 0.3 degrees C (group A) and 35.3 +/- 0.2 degrees C (group B) for the two
      levels of Jtherm, respectively. Arterial blood temperatures increased by 0.4 +/-
      0.4 degree C with mild extracorporeal cooling (group A), whereas arterial blood
      temperatures slightly decreased by -0.1 +/- 0.4 degree C in the group with medium
      negative heat flux (group B) (P < 0.01). Blood pressures tended to drop in the
      warm dialysate group and to remain unchanged in the cool dialysate group (P =
      NS). Relative blood volume changes calculated from on-line ultrasonic blood
      measurements were significantly larger with cool (-12.8 +/- 8.3 vol%) than with
      warm (-7.2 +/- 5.5 vol%, P < 0.05) dialysate, indicating reduced fluid removal
      from peripheral body compartments during cool hemodialysis ultrafiltration.
      Despite the larger reduction in intravascular volume, intradialytic hemodynamic
      stability was maintained with extracorporeal cooling and cool dialysate
      prescription.

PMID- 9189865
TI  - Lower probability of patient survival with continuous peritoneal dialysis in the
      United States compared with Canada. Canada-USA (CANUSA) Peritoneal Dialysis Study
      Group.
AB  - In a prospective cohort study of 680 incident continuous peritoneal dialysis (PD)
      patients in North America, dialysis in the United States compared with Canada was
      associated with a relative risk (RR) of death of 1.93 (95% confidence interval
      [CI], 1.14 to 3.28). The 2-yr survival probability was 79.7% in Canada and 63.2%
      in the United States. This difference was not explained by race, age, gender,
      functional status, insulin-dependent diabetes mellitus, history of cardiovascular
      disease (CVD), nutritional status, or adequacy of dialysis. Other potential
      explanatory variables were further evaluated. These included severity of CVD,
      residual renal function, race, differential transfer to hemodialysis or
      transplantation, patient compliance, modality selection bias, and incidence of
      endstage renal disease requiring dialysis. Cardiovascular morbidity and
      peritonitis probabilities were compared. The CVD severity index was not different
      between countries; the RR risk associated with dialysis in the United States
      remained high at 1.87 (95% CI, 1.09 to 3.19). Residual renal function at
      initiation of dialysis was not different between countries. The 2-yr survival for
      Caucasians was 77% in Canada and 55% in the United States. There was no
      difference in the probability of transfer to hemodialysis or transplantation. The
      RR of a nonfatal cardiovascular event in the United States compared with Canada
      was 1.80 (95% CI, 1.21 to 2.67). There was no difference in time to first
      peritonitis. The observed to predicted creatinine ratio, as an estimate of
      compliance, was 1.13 in Canada and 1.00 in the United States. The prevalence of
      PD in the study centers was 48% in Canada and 22% in the United States. The
      incidence of new dialysis patients in 1992 was 100/million population in Canada
      compared with 211/ million in the United States. The survival difference is not
      explained by age, gender, insulin-dependent diabetes mellitus, nutritional
      status, or adequacy of dialysis. Neither is it explained by race, severity of
      CVD, transfer to hemodialysis, transplantation, or an estimate of compliance. The
      lower proportion of patients receiving PD in the United States may represent a
      selection bias of uncertain direction. The higher acceptance rate for dialysis in
      the United States may explain, in part, the greater cardiovascular morbidity and
      the decreased survival observed.

PMID- 9189866
TI  - The meeting, the society, and the future: where do we go from here?

PMID- 9189867
TI  - 1996 Homer Smith Award Lecture. Cum grano salis: the epithelial sodium channel
      and the control of blood pressure.

PMID- 9189868
TI  - Considerations for the treatment of secondary hyperparathyroidism in renal
      failure.

PMID- 9189869
TI  - Studies on the movement of water through the isolated toad bladder and its
      modification by vasopressin. 1962.

PMID- 9189870
TI  - 1996 nephrology curriculum: American Society of Nephrology.

PMID- 9189871
TI  - Nephrology core curriculum. The American Society of Nephrology and the American
      Society of Nephrology Training Program Directors Committee.

PMID- 9189872
TI  - Mannitol-induced acute renal failure.
AB  - The osmotic diuretic mannitol may be used in diverse clinical settings, such as
      providing "renal protection" in patients at risk for acute renal failure,
      decreasing intracranial pressure in patients with intracranial trauma, and
      preventing the dialysis-disequilibrium syndrome. Mannitol is commonly used after
      cardiac catheterization, cardiovascular surgery, and exposure to intravenous
      contrast dyes. This study presents a case in which a long-term renal transplant
      recipient receiving cyclosporine therapy concomitantly developed acute renal
      failure after the administration of high-dose mannitol in an attempt to induce an
      osmotic diuresis. The diagnosis of "osmotic nephrosis" was confirmed by renal
      biopsy, and the condition was reversed by cessation of the agent. Studies in
      experimental animals indicate that cyclosporin A can potentiate the tubular
      toxicity of mannitol, but such an association has not been verified in humans.
      Numerous studies confirm the nephrotoxic potential of high-dose mannitol,
      especially in patients with renal insufficiency. The clinical utility of the
      osmolar gap in preventing mannitol nephrotoxicity is emphasized.

PMID- 9189873
TI  - Renal papillary necrosis in a patient with sickle cell trait.
AB  - A patient with sickle cell trait who presented with gross hematuria and was
      subsequently found to have renal papillary necrosis is presented. The hematuria
      resolved with conservative therapy consisting of bed rest and hydration with
      hypotonic intravenous fluids. The pathophysiology of renal abnormalities
      associated with sickle cell trait is described. The management of the primary
      clinical manifestations of this disorder, hematuria and papillary necrosis, are
      discussed.

PMID- 9189875
TI  - Diffusion-weighted MRI of myelination in the rat brain following treatment with
      gonadal hormones.
AB  - Previous studies have demonstrated the ability of high-resolution diffusion
      weighted MRI to show maturation of white-matter structures in the developing rat
      brain. The purpose of this study was to investigate the influence of gonadal
      steroid hormones on the rate of this development. Starting from their second
      postnatal day, 16 rat-pups of either sex were repeatedly treated with
      subcutaneous implants containing 17-beta estradiol or delta-androstene 3,17
      dione, respectively. Serial T1-, T2- and diffusion-weighted MRI was performed
      weekly for 8 weeks using a 4.7 T unit. Maturation of anterior optic pathways and
      hemisphere commissures was assessed. Diffusion-weighted images were processed to
      produce "anisotropy index maps", previously shown to be sensitive to white-matter
      maturation. Compared with untreated rat-pups, estrogen-treated animals showed
      accelerated, and testosterone-treated animals delayed maturation on anisotropy
      index maps and histological sections. In all animals, maturational changes
      appeared earlier on anisotropy index maps than on other MRI sequences or on
      myelin-sensitive stained sections. Diffusion-weighted imaging, and the
      construction of spatial maps sensitive to diffusion anisotropy, seem to be the
      most sensitive approach for the detection of maturational white-matter changes,
      and thus may hold potential for early diagnosis of temporary delay or permanent
      disturbances of white-matter development.

PMID- 9189874
TI  - Localised proton MR spectroscopy of brain metabolism changes in vegetative
      patients.
AB  - We examined 14 vegetative brain-injured patients with proton magnetic resonance
      single-volume spectroscopy (1H MRS) at 1.5 T to establish whether there were
      changes in relative concentrations of N-acetyl aspartate (NAA), choline (Cho) and
      creatine (CR) metabolites from those found in healthy brains. Spectra were
      obtained from two different (2 x 2 x 2 cm) volumes of interest in the left and in
      the right frontal cortex, normal on MRI. All spectra revealed abnormalities
      compared with normal spectra obtained from age-matched control subjects. Values
      outside the normal range for at least one of the metabolite ratios were observed
      in all patients. Cho/Cr was markedly higher and NAA/Cho and NAA/Cr were markedly
      lower than in the control subjects. At different times six patients regained
      awareness and the ability to obey commands, and four were re-examined; changes in
      metabolite ratios were observed, which were different in individual patients. The
      NAA/Cho ratio reaches statistical significance in discriminating between the
      patients with a poor outcome (death or prolonged vegetative state) and those who
      regained awareness; the dividing line appears to be at a value of about 1.6.

PMID- 9189876
TI  - Effects of portal-systemic shunt embolization on the basal ganglia: MRI.
AB  - We report MRI in a patient with portal-systemic encephalopathy, in which the high
      signal in the basal ganglia on T1-weighted images showed marked resolution after
      successful embolization of the intrahepatic portal-systemic venous shunt.

PMID- 9189877
TI  - MRI and MR angiography of vertebral artery dissection.
AB  - A review of 4,500 angiograms yielded 11 patients with dissection of the vertebral
      arteries who had MRI and (in 4 patients) MR angiography (MRA) in the acute phase
      of stroke. One patient with incidental discovery at arteriography of asymptomatic
      vertebral artery dissection and two patients with acute strokes with MRI and MRA
      findings consistent with vertebral artery dissection were included. Dissection
      occurred after neck trauma or chiropractic manipulation in 4 patients and was
      spontaneous in 10. Dissection involved the extracranial vertebral artery in 9
      patients, the extra-intracranial junction in 1, and the intracranial artery in 4.
      MRI demonstrated infarcts in the brain stem, cerebellum, thalamus or temporo
      occipital regions in 7 patients with extra- or extra-intracranial dissections and
      a solitary lateral medullary infarct in 4 patients (3 with intracranial and 1
      with extra-intracranial dissection). In 2 patients no brain abnormality related
      to vertebral artery dissection was found and in one MRI did not show subarachnoid
      haemorrhage revealed by CT. Intramural dissecting haematoma appeared as
      crescentic or rounded high signal on T1-weighted images in 10 patients examined 3
      20 days after the onset of symptoms. The abnormal vessel stood out in the low
      signal cerebrospinal fluid in intracranial dissections, whereas it was more
      difficult to detect in extracranial dissections because of the intermediate-to
      high signal of the normal perivascular structures and slow flow proximal and
      distal to the dissection. In two patients examined within 36 h of the onset,
      mural thickening was of intermediate signal intensity on T1-weighted images and
      high signal on spin-density and T2-weighted images. MRA showed abrupt stenosis in
      2 patients and disappearance of flow signal at and distal to the dissection in 5.
      Follow-up arteriography, MRI or MRA showed findings consistent with occlusion of
      the dissected vessel in 6 of 8 patients.

PMID- 9189878
TI  - Topographic anatomy of paraclinoid carotid artery aneurysms: usefulness of MR
      angiographic source images.
AB  - We evaluated the usefulness of magnetic resonance angiography (MRA) for showing
      the topography of paraclinoid carotid artery aneurysms in 27 patients with 30
      paraclinoid aneurysms undergoing conventional angiography, three-dimensional time
      of-flight MRA and surgery. The anatomy shown on the axial MRA source images was
      consistent with that found at surgery. The neck of the aneurysm could always be
      identified on the source images, while it could not be analysed exactly on
      conventional angiography in 3 cases (10%). The optic nerves, including those
      displaced by the aneurysm, were recognised in all patients. The anterior clinoid
      process was shown as a low-intensity rim or area contiguous with the cortical
      bone. The source images were of great value in understanding the topography of
      paraclinoid carotid artery aneurysms.

PMID- 9189879
TI  - Extracranial distal aneurysm of posterior inferior cerebellar artery.
AB  - An unusual aneurysm arising from an extracranial lateral medullary segment of the
      posterior inferior cerebellar artery (PICA) is reported. The origin of the PICA
      was also extracranial, 10 mm below the foramen magnum. The aneurysm was not seen
      on three-vessel angiography. The literature is reviewed with regard to the
      clinical and radiological features of such aneurysms. Occipital and nuchal
      headache with an altered level of consciousness, intraventricular haemorrhage,
      and hydrocephalus are suggestive of such aneurysm. The need for four-vessel
      angiography is again stressed.

PMID- 9189880
TI  - MRI of high-grade glial tumors: correlation between the degree of contrast
      enhancement and the volume of surrounding edema.
AB  - Contrast enhancement of malignant gliomas and the development of peritumoral
      edema are thought to be due to a breakdown of the blood-brain barrier (BBB). The
      degree to which these two factors are related to each other or to the degree of
      damage to the BBB is unknown. Our purpose was to quantitatively correlate the
      degree of enhancement with Gd-DTPA of anaplastic gliomas and glioblastoma
      multiforme with the volume of surrounding edema. In 14 patients, quantitative
      measurements of the volume of peritumoral edema and the degree of contrast
      enhancement were made. A high degree of correlation was found (r = 0.86, P <
      0.01). These results can be viewed as indirect, radiological evidence that edema
      production is quantitatively related to the degree of breakdown of the BBB as
      determined by gadolinium enhancement. These results imply that the origin of the
      edema is in the area of breakdown of the BBB.

PMID- 9189882
TI  - MRI of atlanto-odontoid osteoarthritis.
AB  - We present the MRI appearances of advanced degenerative changes at the atlanto
      odontoid (AO) joint. Changes including obliteration of the joint space,
      subchondral sclerosis and osteophytosis were clearly depicted on fast gradient
      echo T1-weighted MRI images. Recognition of these changes may be helpful in the
      diagnosis in patients with suboccipital pain.

PMID- 9189881
TI  - Pituitary stalk meningioma: case report.
AB  - We report a 45-year-old woman with a meningioma which was in contact with only
      the pituitary stalk on MRI. As the pituitary stalk has no dura mater, we suggest
      this tumour may have originated from the arachnoid membrane of the pituitary
      stalk. Though some reports have shown that meningiomas can arise from sites
      lacking a dural component, this is the first report of a meningioma originating
      from the pituitary stalk.

PMID- 9189883
TI  - MRI of intramedullary sarcoidosis: follow-up of a case.
AB  - Intramedullary lesions are infrequently the first manifestation of sarcoidosis.
      We present clinical and radiological follow-up of spinal cord sarcoidosis in a 68
      year-old woman, mimicking an intramedullary tumour. MRI revealed an unusual area
      of low signal intensity on T2-weighted spin-echo images at the core of the
      lesion, consistent with calcification. Clinical and MRI follow-up showed
      progressive resolution of the intraspinal lesion, except for the calcification,
      with oral steroid therapy.

PMID- 9189884
TI  - The endovascular approach in the management of patients with multiple
      intracranial aneurysms.
AB  - To investigate the role of endovascular treatment we performed a retrospective
      study of our patients with multiple intracranial aneurysms seen in our
      institution between October 1992 and March 1995. This period was chosen to study
      a homogeneous group of patients since the appearance of controlled detachable
      coils, and to obtain the largest number of patients with angiographic follow-up
      of the aneurysms treated. We studied 53 patients with a total of 128 aneurysms,
      in 46 of whom we treated 67 aneurysms by the endovascular approach. Of these, 5
      aneurysms in 3 patients were treated by occlusion of the parent vessel and 62
      aneurysms in 43 patients with coils, 52 with Guglielmi detachable coils and 10
      with mechanically detachable spirals. Complete occlusion was obtained in 58
      aneurysms, and partial occlusion in 9. The therapy caused permanent neurological
      deficit in 3 cases (6.5%), and there was 1 case of rebleeding (incomplete
      occlusion of the aneurysm). No deaths occurred. All aneurysms were treated in 29
      of the 53 patients. Endovascular procedures were used for 16 patients (30%),
      surgery was performed in 1 patient (2%) and the two were combined in 12 (23%). In
      23 of 53 cases (43%), unruptured aneurysms were left untreated, usually because
      of their small size. In 1 patient with unruptured aneurysms, the endovascular
      approach failed and the patient refused surgery.

PMID- 9189885
TI  - Bilateral cavernous carotid artery aneurysms in a 4-year-old child: endovascular
      treatment with mechanically detachable coils.
AB  - We present a 4-year-old child who suffered bilateral third nerve palsies
      secondary to bilateral giant saccular cavernous carotid artery aneurysms.
      Endovascular treatment was performed by means of direct endosaccular aneurysm
      occlusion on the right side and parent vessel occlusion on the left, using
      mechanically detachable coils. No complication occurred during or after the
      procedure. The bilateral third nerve palsies resolved over 3 months. Follow-up
      angiography at 1 year is presented.

PMID- 9189886
TI  - MRI of neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological
      study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile or
      late infantile type.
AB  - Postmortem MRI was carried out on the formalin-fixed brains of 14 patients with
      juvenile (JNCL) and two with late infantile neuronal ceroid lipofuscinosis, one
      of variant and the other of classical type. Two patients with JNCL had also
      undergone MRI during life. After MRI, specimens for histopathological analysis
      were taken from standard areas of the cerebral cortex, deep nuclei and white
      matter. The signal intensity of the periventricular white matter was usually
      higher than that of the peripheral white matter, a finding which correlated with
      the severe periventricular loss of myelin and gliosis observed histologically.
      The signal intensity was usually lower in the thalamus than in the putamen; in
      some patients the signal intensity of the thalamus was equal to or even lower
      than that of the white matter. However, myelin loss, gliosis, the storage process
      or neuronal loss in the thalamus did not correlate with the MRI findings. Since
      in one patient with JNCL the ante- and postmortem MRI did not differ basically,
      it appears probable that the periventricular changes detected in vivo on MRI are
      due to the severe loss of myelin and gliosis observed in this study. However,
      changes resulting from the fixation process must be considered, when postmortem
      and in vivo MRI are correlated.

PMID- 9189887
TI  - Improved detection of cortical and subcortical tubers in tuberous sclerosis by
      fluid-attenuated inversion recovery MRI.
AB  - We carried out fluid-attenuated inversion recovery (FLAIR) pulse sequences with
      long repetition and echo times in seven children with tuberous sclerosis, and
      compared them with conventional spin-echo (SE) sequences. FLAIR images exhibited
      higher sensitivity than conventional SE images to cortical and subcortical
      tubers. The low signal intensity of cerebrospinal fluid on FLAIR images allowed
      more accurate delineation of the cortical and subcortical tubers. However, T1
      weighted imaging was still superior for delineation of subependymal nodules.

PMID- 9189888
TI  - MRI of the brain and craniocervical junction in Morquio's disease.
AB  - We reviewed MRI of the brain and cervical spine in 11 patients with Morquio's
      disease. No abnormality was seen in the brain. The odontoid peg was abnormal in
      all patients, with varying degrees of cord compression due to an anterior soft
      tissue mass and indentation by the posterior arch of the atlas. The degree of
      cord compression was more marked than suggested by the symptoms and signs. We
      recommend MRI of the cervical spine in children with Morquio's disease before the
      development of neurological symptoms, to optimise the timing and type of surgical
      intervention.

PMID- 9189891
TI  - ATP induces Ca2+ release from IP3-sensitive Ca2+ stores exclusively in large DRG
      neurones.
AB  - PURINORECEPTOR-MEDIATED intracellular Ca2+ release was studied in freshly
      isolated adult mouse dorsal root ganglia (DRG) neurones. The cytoplasmic Ca2+
      concentration ([Ca2+]i) was measured using indo-1-based microfluorimetry. The
      application of 100 microM ATP in Ca(2+)-free solution triggered an increase in
      [Ca2+]i in 93% of large DRG neurones but in no small ones. The ATP-induced
      [Ca2+]i transients in large neurones were inhibited by cells incubation with
      thapsigargin or by intracellular dialysis with heparin-containing solution. The
      ATP-triggered increase in [Ca2+]i was not mimicked by adenosine and was blocked
      by suramin, suggesting the involvement of metabotropic (PZY) purinoreceptors. We
      conclude that large (proprioceptive) DRG neurones express PZY purinoreceptors
      linked to the inositol 1,4,5-triphosphate-Ca2+ intracellular signal transduction
      cascade, whereas small (nociceptive) DRG neurones are devoid of such a mechanism.

PMID- 9189890
TI  - The effects of Na+ channel blockers on somatosensory processing by rat dorsal
      horn neurones.
AB  - Two voltage-activated Na+ channel blockers, lamotrigine and flunarizine were
      applied ionophoretically to extracellularly recorded dorsal horn neurones to
      assess effects on activation by noxious (mustard oil) and innocuous (brush)
      stimuli. Lamotrigine and flunarizine caused significantly greater reductions in
      mustard oil-evoked activity (> 50% in both cases) than in brush-evoked activity
      (13 +/- 7% and 29 +/- 6%; p < 6%; +/- 0.005 and p < 0.05 respectively) at
      equivalent ionophoretic currents. Similar results were observed when lamotrigine
      was administered i.v. Thus, the activation of dorsal horn neurones by nociceptive
      and non-nociceptive afferent inputs can be differentiated by the blockade of a
      lamotrigine/flunarizine-sensitive Na+ channel, at a spinal site.

PMID- 9189892
TI  - Marked decrease of immunolabelled 68 kDa neurofilament (NF-L) proteins in brains
      of opiate addicts.
AB  - NEUROFILAMENT (NF) proteins, the major components of the neuronal cytoskeleton,
      have been shown to represent previously unknown targets for the chronic effects
      of morphine in rats. This study was designed to evaluate the abundance of
      immunoreactive NF-L (68 kDa) proteins in post-mortem brains of chronic opiate
      addicts who had died of a heroin or methadone overdose. Levels of NF-L proteins
      were assessed by immunoblotting techniques. Levels of immunoreactive NF-L
      proteins were markedly decreased (47%, n = 17) in the frontal cortex. The reduced
      abundance of brain NF-L proteins was not related to the post-mortem delay or to
      the plasma concentrations of opiates, suggesting that the observed changes
      represent a specific long-term effect of opiate drugs. Because of the functions
      associated with NF proteins (e.g. axonal transport), this finding suggests that
      opiate drugs may induce neuronal damage after chronic abuse in humans.

PMID- 9189893
TI  - [U-13C]glutamate metabolism in rat brain mitochondria reveals malic enzyme
      activity.
AB  - 13C nuclear magnetic resonance spectroscopy was used to study the activity of
      malic enzyme in isolated brain mitochondria from rat in the presence of
      unlabelled malate and [U-13C]glutamate. ADP, inorganic phosphate, malate and [U
      13C]glutamate were added to a suspension of oxygenated mitochondria. Typical
      tricarboxylic acid (TCA) cycle constituents (malate, 2-oxoglutarate and
      succinate) were labelled from [U-13C]glutamate and detected in the superfusion
      medium. The labelling patterns in the different atom positions of glutamate
      revealed entry of both unlabelled and labelled acetyl-CoA into the TCA cycle.
      Unlabelled acetyl-CoA was derived via pyruvate from exogenously applied malate by
      the action of mitochondrial malic enzyme, while labelled acetyl-CoA was derived
      from TCA cycle intermediates, most likely by the action of mitochondrial malic
      enzyme on malate produced from [U-13C]glutamate. The results demonstrate malic
      enzyme activity and pyruvate recycling in isolated rat brain mitochondria.

PMID- 9189894
TI  - Working memory failure by combined blockade of muscarinic and beta-adrenergic
      transmission in the rat hippocampus.
AB  - INTRAHIPPOCAMPAL administration of the muscarinic acetylcholine receptor
      antagonist scopolamine at a dose of 3.2 micrograms/side significantly increased
      the number of errors (attempts to pass through two incorrect panels of the three
      panel-gates at four choice points) in the working memory task with a three-panel
      runway setup, whereas 0.32 microgram/side scopolamine did not affect working
      memory errors. The beta-adrenoceptor antagonist propranolol (10 mg/kg, i.p.) had
      no effect on working memory error, but it produced a significant increase in
      working memory errors when administered in combination with intrahippocampal
      scopolamine at the behaviourally ineffective dose (0.32 microgram/side). The
      increase in working memory errors induced by intrahippocampal administration of
      0.32 microgram/side scopolamine to rats treated with 10 mg/kg propranolol was
      decreased by concurrent injection of the cholinesterase inhibitor physostigmine
      (3.2 micrograms/side). D-Cycloserine (the partial agonist at the glycine bindings
      site on the NMDA receptor/channel complex) at a dose of 10 micrograms/side
      reduced the increase in working memory errors induced by intrahippocampal 0.32
      microgram/side scopolamine combined with 10 mg/kg propranolol. These results
      suggest that neural mechanisms regulated cooperatively by hippocampal muscarinic
      and beta-adrenergic transmission underlie working memory performance, and that
      modification of NMDA function contributes to such interactive regulation of
      working memory processes in the hippocampus.

PMID- 9189896
TI  - ERPs to encoding and recognition in two different inter-item association tasks.
AB  - EVENT-RELATED potentials were obtained during study and recognition of word pairs
      in an incidental learning paradigm. Word pairs were studied either by performing
      a semantic judgment separately for each word (non-associative encoding) or by
      creating a semantic association between the two words (associative encoding).
      Only word pairs encoded associatively elicited a reliable dm-effect with a right
      frontal maximum. Recognition of previously studied word pairs revealed two
      topographically and temporally distinct old/new effects: an earlier parietal
      effect which was only reliable for associatively encoded items and a right
      frontal effect which was of equal magnitude for word pairs from both encoding
      tasks. The findings suggest that ERP effects of distinct memory processes are
      differentially influenced by the encoding instructions.

PMID- 9189895
TI  - Sleep deprivation increases brain serotonin turnover in the rat.
AB  - IN order to study possible time-dependent changes in serotonin metabolism in rat
      brain, male Wistar rats were subjected to 3, 6 or 12 h total sleep deprivation
      (SD) by gentle handling. In addition two groups of rats subjected first to 6 h SD
      were allowed 2 or 4 h rebound sleep. Tissue concentrations of serotonin (5-HT)
      and 5-hydroxyindoleacetic acid (5-HIAA) were measured from several brain areas
      using HPLC/ECD. SD significantly increased the 5-HIAA/5-HT ratio in frontal
      cortex, hippocampus, hypothalamus and brain stem, indicating increased 5-HT
      turnover in those areas. After 2 and 4 h rebound sleep, the 5-HIAA/5-HT ratio was
      similar to that in controls. We conclude that a short SD increases 5-HT turnover
      in the rat brain for the duration of SD only.

PMID- 9189897
TI  - Autonomous cortical rhythms affect temporal modulation transfer functions.
AB  - A correlational study between the dominant frequencies in the spontaneous local
      field potential and the single unit's best modulation frequency (BMF) for
      periodic click train stimulation in the primary auditory cortex of the cat is
      presented. Data were obtained from 251 single units recording in 29 cats. The
      correlation between spindle frequency (mean 8.2 Hz) and BMF (mean 9.3 Hz) was
      significant (r2 = 0.58, p < 0.0001). The limiting click-following rate was
      negatively correlated with the strength of the spindle rhythm: the longer the
      oscillation the lower the limiting rate. This suggests that the click-following
      responses of the primary auditory cortex depends as much on ongoing autonomous
      activity as it does on stimulus-induced activity.

PMID- 9189898
TI  - Category-specific anomia: implication of different neural networks in naming.
AB  - The occurrence of anomia specifically affecting the ability to name animals is
      described in three patients. This deficit is contrasted with their capacity to
      name actions and tools. It is suggested that it is easier to access the names of
      'operative' items, which were learned through both visual and sensorimotor
      experience, than the names of 'figurative' items, which were primarily learned
      through the visual modality. This hypothesis is consistent with the infero
      temporal location of brain damage in these patients. Their ability to retrieve
      knowledge about operative items is assumed to be due to the sparing of the
      occipito-parietal area. Because the impairment also involves the recognition of
      animals, the likely locus of damage is the semantic component of the processing
      system.

PMID- 9189899
TI  - Is MK-801 neuroprotection mediated by systemic hypothermia in the immature rat?
AB  - Hypothermia after hypoxia-ischaemia (HI) confounds the interpretation of the
      effects of neuroprotective drug intervention. The effect of 0.5 mg/kg of
      dizocilpine (MK-801) administered after HI on rectal temperature at 2-36 h and on
      brain damage 2 weeks after the insult was evaluated in the immature rat. In pups
      kept at an ambient temperature of 21 degrees C, MK-801 lowered the temperature by
      1.1 degrees C and reduced the brain damage by 45%. In pups held at an ambient
      temperature of 33 degrees C, MK-801 treatment afforded a 34% reduction of brain
      damage without lowering the rectal temperature. In conclusion, the
      neuroprotection offered by MK-801 does not depend on systemic hypothermia in this
      model.

PMID- 9189900
TI  - Differential expression of transcription factors in the accumbens of an animal
      model of ADHD.
AB  - Transcription factors have been used as neuronal markers in the nucleus accumbens
      (ACB) of male juvenile spontaneously hypertensive rats (SHR), an animal model of
      attention-deficit hyperactivity disorder (ADHD), to trace putative neural
      substrates. In SHR, immunocytochemistry and PC-assisted image analysis showed
      lower expression of pan-fos, c-fos, zif/268 in the shell, and the c-fos and
      zif/268 in the core, with an increased level of Jun-B in the core. The
      differential lower basal expression of transcription factors in the ACB of an
      animal model of ADHD implies a reduced number of modules and might represent a
      neural substrate of the attention deficits seen in SHR and children with ADHD at
      low motivational levels.

PMID- 9189902
TI  - Identification of a novel glial fibrillary acidic protein mRNA isotype related to
      memory retention in rats.
AB  - Using the polymerase chain reaction (PCR) differential display directed to
      cloning transcripts related to retention performance for the inhibitory avoidance
      learning task, we have isolated two rat cDNA fragments homologous to the 3'
      untranslated region (3'UTR) of glial fibrillary acid protein (GFAP) cDNA. The
      GFAP upper cDNA represents a new GFAP mRNA isotype which has a 7 bp insertion in
      the 3'UTR. Further analyses indicated that retention performance in rats
      containing only the new GFAP mRNA isotype was significantly better than that of
      rats containing both the new GFAP mRNA isotype and the standard GFAP mRNA
      simultaneously. These results suggest that expression of the GFAP isotypes may be
      related to memory retention in rats.

PMID- 9189901
TI  - NGF involvement in pain induced by chronic constriction injury of the rat sciatic
      nerve.
AB  - Chronic constriction injury (CCI) of the rat sciatic nerve, which within 3 days
      induces thermal and mechanical hyperalgesia and mechanical allodynia, is used as
      a model for pain resulting from nerve injury. Involvement of nerve growth factor
      (NGF) in the development of this hyperalgesia is suggested by the increase in the
      level of mRNA encoding NGF in cells in the injured area and in dorsal root
      ganglia at the level of the lesion and the greatly increased NGF levels
      (determined by ELISA) in the ganglia ipsilateral to the CCI. Application of anti
      serum to NGF at the site of CCI delayed the appearance of hyperalgesia, whereas
      pre-immune serum appeared to enhance it. These results are consistent with the
      view that NGF is an important factor in the appearance of hyperalgesia associated
      with unilateral mononeuropathy.

PMID- 9189903
TI  - Subthalamic stimulation elicits hemiballismus in normal monkey.
AB  - High frequency stimulation (HFS) of the subthalamic nucleus (STN) reduces
      parkinsonian symptoms in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      treated monkey and in human patients. The effects of stimulation on normal waking
      primates have never been evaluated. While low frequency stimulation has no
      effect, HFS induces dyskinesias contralateral to the stimulated STN resembling
      human hemiballismus and those obtained in primates after neurotoxic lesion or
      pharmacological blockade of the STN. In the normal monkey, HFS appears reversibly
      to incapacitate the STN and allow the emergence of involuntary proximal
      displacements, due to disinhibition of the thalamo-cortical pathway. In the MPTP
      treated monkey HFS buffers STN overactivity and alleviates akinesia and rigidity
      by reducing inputs to the internal segment of the globus pallidus.

PMID- 9189904
TI  - Unusual responses to light and darkness of ocular melatonin in European sea bass.
AB  - Regulation by light and darkness of melatonin rhythms in the plasma and eye of
      the European sea bass (Dicentrarchus labrax) was studied. During light-dark
      cycles, plasma and ocular melatonin exhibited day-night changes with higher
      levels at mid-dark and at mid-light, respectively. Circulating melatonin levels
      were low in constant light but high in constant darkness (DD); ocular melatonin
      levels showed the reverse pattern. Plasma melatonin exhibited circadian rhythm
      for 1 cycle but the rhythm was no longer apparent on day 2. There was no
      circadian rhythm in ocular melatonin. Acute light exposure in DD decreased plasma
      melatonin but increased ocular melatonin. These results suggest that circulating
      melatonin may be used as a signal for darkness but ocular melatonin is used as a
      signal for the light phase.

PMID- 9189905
TI  - Relation of cerebral blood flow velocity and level of vigilance in humans.
AB  - Blood flow velocities in both middle cerebral arteries (MCA) were measured using
      transcranial Doppler ultrasound (TCD) in healthy subjects engaged in a continuous
      static visual vigilance task. Stimuli comprised white vertical gratings on a
      black background with a size of 5 x 5" (non-targets) or 5 x 3.5" (targets).
      Button presses were required to the rare (8.5%) targets. Over the 30 min session
      a decrease in hit rate and an increase in reaction time were seen, indicating a
      decrease in vigilance. These performance changes were paralleled by a decrease in
      flow velocity in both MCAs. No hemispheric difference was seen. These data
      suggest a close coupling of performance and blood flow in vigilance tasks.
      Modulation of cholinergic activity during the vigilance task might be the common
      underlying mechanism.

PMID- 9189906
TI  - LIF potentiates the NT-3-mediated survival of spiral ganglia neurones in vitro.
AB  - The survival of auditory neurones depends on the continued supply of trophic
      factors. Early postnatal spiral ganglion cells (SGC) in a dissociated cell
      culture were used as a model of auditory innervation to test the trophic factors
      leukaemia inhibitory factor (LIF) and neurotrophin-3 (NT-3) for their ability,
      individually or in combination, to promote neuronal survival. The findings
      suggest that LIF supports neuronal survival in a concentration-dependent manner.
      Moreover LIF potentiated NT-3-mediated spiral ganglion neuronal survival in a
      synergistic fashion.

PMID- 9189907
TI  - Allelic variability in D21S11, but not in APP or APOE, is associated with
      cognitive decline in Down syndrome.
AB  - Genetic variation in the APOE gene and variation in chromosome 21 genotypes,
      including the APP locus, may influence age-associated cognitive decline in adults
      with Down syndrome. Molecular genetic and longitudinal neuropsychological
      analysis was performed for 41 unrelated Caucasian individuals (mean age 48.1 +/-
      1.1 years (s.c.m.)) with free trisomy 21. Allele frequencies and genotype
      distributions were compared among subgroups with or without evidence of cognitive
      decline. Genetic variability at APOE and APP was not significantly associated
      with evidence of cognitive decline. However, aged individuals with Down syndrome,
      without evidence of cognitive decline, demonstrated unusual allelic variability
      at D21S11. These findings are discussed in the context of current hypotheses of
      Alzheimer-type dementia in Down syndrome and in the general population.

PMID- 9189908
TI  - Corticopontine terminal fibres form small scale clusters and large scale lamellae
      in the cat.
AB  - We investigated whether terminal fibres in the pontine nuclei are arranged in a
      lamellar pattern like that demonstrated earlier for pontocerebellar neurones.
      Following tracer injections in visual and parietal cortices and subsequent
      computer-based 3-D analysis, we found that labelled corticopontine terminal
      fibres form numerous sharply delimited aggregates of variable shape. Several of
      the aggregates are cylindroids (diameter 200-300 microns, length 1-3 mm). The
      aggregates are confined to a lamellar subspace, the position of which depends on
      the anteroposterior location of the cortical injections. These findings suggest
      that the cerebroponto-cerebellar system may be organized according to fairly
      simple, topographical rules. We discuss the implications of our results in
      relation to the development of corticopontine topographical organization.

PMID- 9189909
TI  - Human cortico-hippocampal activity related to auditory discrimination revealed by
      neuromagnetic field.
AB  - We carried out multi-dipole estimation and pursued spatio-temporal brain activity
      on a time scale of several milliseconds during an auditory discrimination task
      using a whole-cortex type SQUID system. Neuronal activities were estimated in the
      medial (hippocampus, parahippocampal gyrus, etc.) and lateral temporal cortices
      (superior and middle temporal gyri, etc.), the dorsolateral prefrontal cortex
      (middle and inferior frontal gyri, etc.) and the parietal cortex (supramarginal
      gyrus, etc.) in the 280-400 ms latency range. The activity in the posterior
      hippocampal region was the most prominent and long-lasting in parallel with the
      activities in the other regions. Therefore, the posterior hippocampal region is a
      central structure engaged in auditory discrimination. The whole-cortex
      neuromagnetic measurements provided the possibility of imaging the time-varying
      activities of the human cortico-hippocampal neural networks.

PMID- 9189910
TI  - Physical damage to rat cortical axons mimics early Alzheimer's neuronal
      pathology.
AB  - We investigated the reactive cytoskeletal changes following physical damage to
      axons in the rodent neocortex and compared these with the earliest neuronal
      alterations seen in Alzheimer's disease (AD). Insertion of a 25 gauge needle into
      the rodent somatosensory cortex resulted in ring- and club-like axonal changes
      characterized by an accumulation of neurofilaments. Morphologically and
      neurochemically identical abnormal axons were present within neocortical beta
      amyloid deposits of individuals in the early stages of AD. Physically damaged rat
      cortical axons may therefore serve as a model for the early neuronal pathology of
      AD. Furthermore, these results suggest that insoluble beta-amyloid deposition may
      physically damage local axons, with further neurofibrillary changes due to the
      reactive neuronal response to this type of injury.

PMID- 9189911
TI  - cAMP modulates an S-type K+ channel coupled to GABAB receptors in mammalian
      respiratory neurons.
AB  - Premotor respiratory neurons from neonatal rats express a Ba(2+)-insensitive
      outward rectifying K+ channel (KOR) which is activated by gamma-aminobutyric acid
      acting at its beta receptor. The biophysical properties of KOR are similar to
      those described for the S-channel (KS) which underlies simple forms of non
      associative learning in the marine mollusc Aplysia. We show here that KOR, like
      the S-channel, is inhibited by cAMP. In addition, we demonstrate that this
      inhibition is due to a change in closed time kinetics. Our data suggests that the
      ionic and biochemical substrates underlying synaptic plasticity in Aplysia have
      been phylogenetically conserved in mammalian motor circuits such as that
      controlling rhythmic breathing movements.

PMID- 9189912
TI  - Implicit processing of somatosensory stimuli disclosed by a perceptual after
      effect.
AB  - A right-brain damaged patient (GR) showing tactile extinction, neglect and no
      hypesthesia, was asked to compare, in 30 trials, the size of two spheres of
      different size simultaneously put into each hand. Accuracy was poor because GR
      was unable to feel the sphere in his left hand and could only report the size of
      the right sphere. GR was then asked to compare two spheres of identical sizes
      although again unable to perceive the left sphere he was deceived by a perceptual
      after-effect also observed in normal subjects, and reported incorrectly the size
      of the right sphere. The left sphere although unperceived, influenced the
      perception of the right hand, thus giving the first evidence for an implicit
      processing of extinguished somatosensory information.

PMID- 9189913
TI  - Expression of SKP1 mRNA and protein in rat brain during postnatal development.
AB  - We previously isolated the cell cycle element SKP1 as a candidate plasticity gene
      in the rat visual cortex. Here, we studied the expression and localization of
      SKP1 mRNA and protein in rat brain. We found a high level of expression for the
      SKP1 gene in the cortex at different postnatal ages. SKP1 mRNA levels remained
      stable from P2 (postnatal day 2) to adulthood. SKP1 mRNA expression was also
      detected in several other brain areas. Skp1p (SKP1 protein) immunohistochemistry
      showed nuclear staining in a large majority of neurones. The pyramidal cells in
      the hippocampus, as well as cortical cells were stained. The presence of Skp1p in
      post-mitotic neurones suggests that this protein is involved in processes other
      than the cell cycles other target proteins and functions in neurones are
      currently under investigation.

PMID- 9189914
TI  - Urine and urine-derived compounds induce c-fos mRNA expression in accessory
      olfactory bulb.
AB  - Soiled bedding from male mice induced c-fos mRNA expression in the accessory
      olfactory bulb (AOB) and main olfactory bulb (MOB) of female mice. The increase
      observed in the AOB, but not the MOB, was dependent on the presence of the
      vomeronasal organ (VNO). Male urine alone also increased c-fos mRNA expression in
      the AOB. The urine-derived compounds dehydro-exo-brevicomin (DHB) and sec-butyl
      dihydrothiazole (SBT) in combination with major urinary protein (MUP) induced
      significantly greater c-fos mRNA expression in the AOB than in the MOB. The
      results indicate that compounds derived from male urine are detected at the AOB
      and suggest that specific urinary compounds play an important role in AOB
      mediated reproductive events.

PMID- 9189915
TI  - Hemispheric asymmetries in global and local processing: evidence from fMRI.
AB  - Functional magnetic resonance imaging (fMRI) was used to explore the brain
      substrate associated with global and local processing of visuospatial patterns.
      Systematic differences in activation, consistent with differences observed in
      reaction time data collected under conditions of visual hemifield presentation,
      were found in occipitotemporal regions of the right and left hemispheres. Within
      the right hemisphere, area of activation and fractional signal changes were
      greater under conditions of global processing than under local processing
      conditions. In the left hemisphere, activation to global and local input was high
      and comparable.

PMID- 9189916
TI  - Neurofilament architecture of superior and mesial premotor cortex in the human
      brain.
AB  - Monoclonal antibody (SMI-32) to neurofilament protein was used in an
      immunochemical study of the premotor cortex of two human brains in comparison
      with other architectonic techniques such as Nissi, myelin, cytochrome-oxidase and
      acetylcholinesterase staining in order to distinguish cortical subdivisions. SMI
      32 immunoreactivity technique provides 'neurofilament architecture' patterns
      specific to area 4, caudal area 6 (area 6c) and rostral area 6 (area 6r).
      Particularly, the distinction between the two subdivisions of area 6, which is
      difficult to appreciate with the usual cytochemical or enzyme architectonic
      techniques, appears very apparent with this technique. Hence, it was possible to
      localize the topographic boundaries of area 6a alpha and 6a beta of the Vogts on
      the dorso-lateral convexity and the supplementary motor area and the
      presupplementary motor area on the mexial wall of the hemisphere.

PMID- 9189917
TI  - Urocortin, a novel neuropeptide with anxiogenic-like properties.
AB  - Potential anxiogenic-like properties of urocortin, a corticotropin-releasing
      factor (CRF)-related neuropeptide, were investigated in models of anxiety in
      rodents. In the elevated plus-maze, CRF- and urocortin-treated rats (0.1 nmol,
      i.c.v.) spent less time and made fewer entries into open arms. In the light-dark
      test in mice, urocortin (0.006-0.06 nmol, i.c.v.) dose-dependently reduced time
      and number of transitions into the lit area. Urocortin also dose-dependently
      (0.02-0.2 nmol, i.c.v.) reduced mice exploratory behaviour in an open field. This
      effect was reversed by diazepam (0.1-1 mg/kg, i.p) and by the CRF receptor
      antagonist alpha-helical CRF (0.8-8 nmole, i.c.v.). These data show that
      urocortin produces anxiety-like effects in several behavioural paradigms in
      rodents.

PMID- 9189918
TI  - Temporal patterns in human epileptic activity are modulated by perceptual
      discriminations.
AB  - We studied subdural recordings from a patient with an unusually focal and stable
      occipito-temporal epileptic discharge under four experimental conditions. The
      series of time intervals between successive spike discharges displayed a few (3
      5) clusters of periodic values representing statistically significant short-term
      periodicities when tested against surrogate data. This short-term predictability
      was modulated during the different experimental conditions by periodicity shifts
      of the order of 15-30 ms. Correspondingly, there was an increased gamma-band (30
      70 Hz) coherence between the epileptic focus and surrounding recording sites. We
      conclude that the focal epileptic activity is part of an extended network of
      neural activities which exert a fast modulation reflected in changes of
      transiently periodic activities.

PMID- 9189919
TI  - Downregulation of metabotropic glutamate receptor 1a in motoneurons after
      axotomy.
AB  - Axotomized motoneurons display drastic modifications in synaptic structure and
      function related to their disconnection from the periphery and establishment of a
      regenerative metabolic functional mode. The molecular basis of these
      modifications is not fully understood. Here we describe changes in metabotropic
      glutamate receptor 1a (mGluR1a)-immunoreactivity 3, 7 or 14 days after unilateral
      aciatic transection. mGluR1a-immunoreactivity was distributed throughout the
      somatic cytoplasm and somatodendritic membrane of uninjured motoneurons and was
      significantly reduced in axotomized motoneurons. This reduction was observed at 3
      days and grew progressively over 2 weeks. These findings suggest that
      downregulation of mGluR1a could contribute to reduced excitatory
      neurotransmission in axotomized motoneurons.

PMID- 9189920
TI  - Processing of presenilin 1 in brains of patients with Alzheimer's disease and
      controls.
AB  - Mutations in the presenilin genes are involved in the aetiology of the majority
      of familial early-onset Alzheimer disease (AD) cases. Presenilin 1 (PS1) is
      proteolytically processed in vivo, resulting in the accumulation of N-terminal
      approximately 27-28 kDa and C-terminal approximately 18 kDa derivatives. To
      examine the metabolism of PS1 in brains of patients with AD harbouring PS1
      mutations I143T and G384A, we performed immunoblot analyses of brain homogenates
      using well characterized antibodies. We document that approximately 27-28 kDa N
      terminal and approximately 18 kDa C-terminal PS1 proteolytic fragments accumulate
      in brain of these individuals, and that in large part the accumulation pattern is
      indistinguishable from that observed in brains from individuals with sporadic AD
      or controls. Notably, little, if any, full-length PS1 was detected in brain
      tissue of patients carrying PS1 mutations or in those with sporadic AD,
      indicating that failed proteolysis of PS1 is not a central feature of
      pathogenesis in these patients.

PMID- 9189921
TI  - Substance P modulates taste responses in the nucleus of the solitary tract of the
      hamster.
AB  - The effects of substance (SP) microinjections on the electrophysiological
      response of gustatory neurons within the nucleus of the solitary tract (NST) were
      examined in hamsters following either anodal electrical or NaCl stimulation of
      the anterior tongue. For both types of stimulation, SP produced excitatory and
      suppressive effects on the activity of gustatory NST neurons, with excitatory
      effects being more common. In response to repetitive anodal stimulation of the
      tongue, the modulatory effect of SP lasted 30-400 s. In the presence of SP, the
      firing rate of 48% of the neurons was increased and that of 9% was decreased
      following NaCl stimulation. This dual action of SP could be due to direct
      excitation of teste-responsive neurons and to excitation of inhibitory local
      circuit neurons which, in turn, decrease the responsiveness of gustatory neurons.

PMID- 9189922
TI  - Functional asymmetry of cortical motor control in left-handed subjects.
AB  - We used positron emission tomography (PET) to investigate which cortical motor
      areas are active in relation to unilateral dominant or non-dominant finger
      movements in left-handed subjects. The right premotor area was activated by both
      contralateral and ipsilateral finger movements, in contrast to the primary motor,
      the left premotor and supplementary motor areas in which activation was only by
      contralateral movements. Bilateral finger movements activated all of these areas.
      We conclude that there exists cortical asymmetry for motor control in left
      handers which is different from that apparent in right-handers.

PMID- 9189923
TI  - Age-related changes in the expression of Alzheimer's beta APP in the brain of
      senescence accelerated mouse (SAM)-P/10.
AB  - Patients with Alzheimer's disease (AD) show loss of memory and cognitive deficits
      the molecular mechanisms of which are not completely known. We examined age
      related changes in the expression levels of beta-amyloid precursor protein (beta
      APP) in the brain of the senescence accelerated mouse (SAM) P/10, which shows age
      dependent brain atrophy and impairment in learning and memory, and in the
      senescence resistant mouse (SAM)-R/1 using reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. Levels of both beta APP mRNA and protein
      increased with age, reaching a peak at 8 months of age in the hippocampus of SAM
      P/10. In contrast, beta APP protein level decreased with age in the hippocampus
      of SAM-R/1 while beta APP mRNA level did not change significantly. Levels of beta
      APP mRNA and protein showed no change with ageing in other brain regions,
      including cerebral cortex, thalamus/midbrain and cerebellum brain stem. These
      results suggest that the beta APP over-expression in the hippocampus might be
      related to the characteristic memory loss in SAM-P/10.

PMID- 9189924
TI  - Long-term survival effects of GDNF on neonatal rat facial motoneurons after
      axotomy.
AB  - Glial cell-line derived neurotrophic factor (GDNF) has survival promoting effects
      on axotomized neonatal motoneurons. We examined how long it could sustain
      motoneurons after postnatal day O (PND) facial nerve axotomy. GDNF, or cytochrome
      c as a negative control, were locally administered by Gelfoam implants at the
      time of axotomy and some were re-implanted on PND 14. The surviving motoneurons
      were quantified on PND 14 and 28. GDNF completely rescued lesioned motoneurons
      from axotomy-induced cell death at 14 days and was still effective (about 40%) at
      PND 28. GDNF also prevented axotomy-induced atrophy at both PND 14 and 28,
      indicating that the neurotrophic effects of GDNF on neonatal motoneurons are long
      term.

PMID- 9189925
TI  - Internally coherent spatial memories in a mammal.
AB  - Children aged 3.5-4.0 years were shown objects being hidden in three different
      locations in a rectangular environment, were disoriented to disable dead
      reckoning, and were asked without feedback where each object was. Results showed
      that children's spatial memories were internally coherents the locations subjects
      chose were in a correct spatial configuration relative to one another as well as
      to environmental geometry, despite the fact that the environment's symmetry would
      have revealed any individual binding of memory for object positions to local
      environmental features. This finding of internal coherence in the spatial
      representation of one mammal is discussed relative to neural and behavioral
      findings on navigation and spatial memory in mammals more generally.

PMID- 9189926
TI  - Attention and probability effects in the human occipital cortex: an optical
      imaging study.
AB  - A new imaging technique (event-related optical signal, EROS) reveals the time
      course of neural activity in selected cortical areas of normal human subjects.
      This technique was used to study the event-related activity in striate and
      extrastriate occipital areas in an experiment in which spatial selective
      attention and stimulus probability were manipulated. The results show that
      attention effects are evident in the initial response in extrastriate cortex
      (latency < 100 ms), but not in striate cortex, confirming previous modeling
      effects. They also show that the initial response in striate cortex is modulated
      by stimulus probability, suggesting the occurrence of pre-attentive memory
      phenomena in primary visual cortex.

PMID- 9189927
TI  - Functional stability of hippocampal slices after treatment with cyclooxygenase
      inhibitors.
AB  - The influence of cyclooxygenase inhibitors on functional stability of hippocampal
      slices, determined by electrophysiological criteria of recovery after slicing and
      long-term maintainence of population activity, was studied. Transient (3 min)
      treatment of slices during slicing with indomethacin (45 microM) or aspirin (0.5
      mM) allowed registration of the population responses from the second minute. The
      activity reached 100% after 15 min incubation and could be registrated for 3 days
      under conditions of overnight hypothermia. The presence of the same drugs for the
      entire incubation period had the same effect. The present findings suggest that
      slicing is a crucial point for triggering of pathological events mediated by
      cyclooxygenase products and that blockade of cyclooxygenase provides for the
      further high longterm functional stability of brain slices.

PMID- 9189928
TI  - Left-hemisphere specialization for the processing of acoustic transients.
AB  - Previous work suggests that speech sounds incorporating short-duration spectral
      changes (such as the formation transitions of stop consonants) rely on left
      hemisphere mechanisms for their adequate processing to a greater degree than do
      speech sounds incorporating spectral changes of a longer duration (such as vowel
      sounds). Ten normal subjects were scanned using positron emission tomography
      while discriminating pure tone stimuli incorporating frequency glides of either
      short or long duration. A comparison of these two conditions yielded significant
      activation foci in left orbitofrontal cortex, left fusiform gyrus, and right
      cerebellum. Because non-linguistic stimuli were used, these foci must reflect
      some basic low level aspect of neural processing that may be relevant to speech
      but cannot be a consequence of accessing the speech system itself.

PMID- 9189929
TI  - Tryptophan is present in glial cells and photoreceptors in the chicken retina.
AB  - Tryptophan is a large neutral amino acid which is utilized in the biosynthesis of
      neuroactive substances such as serotonin and melatonin. However, it has been
      unclear where pools of tryptophan might be localized. Using a specific antiserum
      against tryptophan, we demonstrate that in the chicken retina tryptophan is
      present in radial glial cells and photoreceptors, but not in other neuronal
      elements. These data suggest that serotonergic neurones are probably dependent
      upon the transfer of tryptophan from the glial cells in order to manufacture
      serotonin and other tryptophan derivatives in the brain. If glia do supply
      tryptophan to neurones then this process will have significant practical
      implications for our basic understanding of and pharmacological manipulation of
      serotonergic systems.

PMID- 9189930
TI  - Memory-related changes of nitric oxide synthase activity and nitrite level in rat
      brain.
AB  - The changes of nitric oxide synthase (NOS) activity and nitrite level in rat
      brain regions after spatial learning were investigated. NOS activity was assayed
      by conversion of [3H]L-arginine to [3H]L-citrulline, and a sensitive fluorometric
      assay for quantification of nitrite was used. Compared with sham-trained rats,
      NOS activity and nitrite level in hippocampus and cortex, and also the nitrite
      level in cerebellum, was elevated significantly one day after rats had learnt a
      water-rewarded spatial alteration task. These results suggest a spatial memory
      related changes of endogenous NO in rat brain, and support the idea that NO
      participates in learning and memory processes.

PMID- 9189931
TI  - Interleukin-6 affects scopolamine-induced amnesia, but not brain amino acid
      levels in mice.
AB  - We have previously shown that, after peripheral administration, different
      cytokines affect cognitive functions in mice. In this study, we evaluated the
      effects of mouse interleukin-6 (IL-6) on the classical behavioural test of
      scopolamine-induced amnesia for a passive avoidance response in the mouse.
      Pretraining i.p. administration of this cytokine (0.125 and 0.5 microgram/mouse)
      significantly reduced the amnesic action of the muscarinic receptor antagonist.
      As it is well known that brain amino acids are deeply involved in the modulation
      of cognitive processes we measured the levels of glutamine, aspartic acid,
      glutamic acid and GABA in the hippocampus and hypothalamus of mice treated with
      IL-6. At both doses which affected the cognitive functions, this cytokine had no
      effect on brain levels of measured amino acids. Neither nociceptive thresholds to
      a thermal stimulus, nor spontaneous locomotor activity were modified by the acute
      administration of IL-6 (0.5 microgram/mouse). Our data confirm previous
      observations indicating that peripheral administration of cytokines affects some,
      but not other brain functions and suggest the involvement of IL-6 in the central
      modifications induced by the immune activation.

PMID- 9189932
TI  - Auditory efferents involved in speech-in-noise intelligibility.
AB  - Following studies proposing that medial olivocochlear efferents might be involved
      in the processing of complex signals in noise, we tested the involvement of
      efferent feedback in speech-in-noise intelligibility. Two approaches were used:
      measures of speech-in-noise intelligibility in vestibular neurotomized patients
      with cut efferents and comparison with normal hearing subjects; and correlations
      between effectiveness of olivocochlear feedback, assessed by contralateral
      suppression of otoacoustic emissions and speech-in-noise intelligibility in
      normal subjects. Contralateral noise improved speech-in-noise intelligibility in
      normal ears. This improvement, which was almost absent in de-efferented ears of
      vestibular neurotomized patients, was correlated with the strength of the
      olivocochlear feedback. Together, these results suggest that olivocochlear
      efferents play an antimasking role in speech perception in noisy environments.

PMID- 9189933
TI  - The first neurophysiological evidence for cognitive brain dysfunctions in
      children with CATCH.
AB  - CATCH syndrome, caused by a microdelection in chromosome 22, is characterized by
      cleft palate and cardiac anomalies. The majority of these children also have
      learning difficulties or speech and language deficits. These problems are often
      due to the dysmorphology of the articulatory system. In the present study, the
      duration of auditory sensory memory, which is of central importance to speech
      perception and understanding, was investigated. As a research method we used
      mismatch negativity (MMN), an attention independent event-related potential,
      which provides an objective electrical index of auditory sensory memory. The
      present data suggest that the duration of this memory span is considerably
      shorter in 6-10-year-old children with CATCH than in healthy controls. Thus, the
      language-related problems encountered in children suffering from CATCH syndrome
      are likely to be caused also by CNS dysfunctions.

PMID- 9189935
TI  - Gamma responses in the EEG: elementary signals with multiple functional
      correlates.
AB  - The hypothesis that electric and magnetic brain activity in the gamma range is
      related to cognitive processing is based mainly on experiments with complex
      stimuli. Our report, however, demonstrates the existence of gamma responses to
      "extremely simple" visual stimuli in several intracranial structures of the cat
      brain. This implies that the functional correlates of gamma activity are diverse,
      encompassing cognitive as well as primary sensory processing. The ubiquity of
      gamma responses strongly suggests the universal importance of gamma rhythms as
      functionally relevant elementary signals of the brain.

PMID- 9189934
TI  - Magnetic brain imaging of extinction processes in human classical conditioning.
AB  - By recording neuromagnetic events during aversive classical conditioning, we
      examined the extinction of a previously described conditioned response. Averaging
      over non-reinforced exposures to the conditioned stimulus revealed magnetic
      activity in the secondary somatosensory and insular cortices, appearing between
      110 and 140 ms after the omitted unconditioned electric shock. We suggest this
      activity to be elicited by the discrepancy between shock expectancy and
      perceptual processes associated with the omission of the unconditioned stimulus,
      reflecting one of several brain processes in extinction.

PMID- 9189936
TI  - Management of carcinoma of the superior pulmonary sulcus.
AB  - Tumors of the superior pulmonary sulcus (Pancoast tumors) are bronchogenic
      carcinomas that occur at the thoracic inlet and typically involve, by direct
      extension, the lower trunks of the brachial plexus, the intercostal nerves, the
      stellate ganglion, and adjacent ribs and vertebrae. These tumors are rare,
      comprising 5% of all lung cancers. Treatment of Pancoast tumors has traditionally
      consisted of preoperative radiation to a dose of 3,000 to 4,500 cGy followed by
      surgical resection. Overall 5-year survival rates range from 30% to 50%. Even if
      treatment achieves local disease control, distant failure (brain or bone) is
      common. Recent treatment efforts have focused on the use of induction
      chemoradiation followed by surgery and further chemotherapy. This combined
      modality approach may become the new treatment paradigm for Pancoast tumors.

PMID- 9189937
TI  - Pituitary adenomas: current methods of diagnosis and treatment.
AB  - Pituitary adenomas are benign neoplasms that can be effectively managed by a
      variety of therapeutic options. The clinician's goal in managing patients with
      these tumors should be to minimize the morbidity of each intervention used in
      diagnosis and treatment. Standard diagnostic interventions include MRI, hormonal
      assessment, and tissue diagnosis. Therapies include transsphenoidal surgery,
      external-beam radiotherapy, newer stereotactic irradiation techniques, and
      medical management. Appropriate treatment selection requires detailed knowledge
      of the expected outcomes and side effects of each option. Newer and perhaps less
      toxic treatment techniques are evolving and require further evaluation.

PMID- 9189938
TI  - Use of adjuvant analgesics profiled at pain conference.

PMID- 9189939
TI  - Radiotherapeutic management of medulloblastoma.
AB  - Although craniospinal irradiation has been employed in children with
      medulloblastoma for the past 40 years, many issues concerning its use have been
      raised and examined, and some continue to be debated. Careful radiation technique
      includes adequate irradiation of the neuraxis with special attention to the
      cribriform plate region and termination of the thecal sac. Conventional-dose
      craniospinal radiation therapy, in combination with chemotherapy, is currently
      recommended for patients with high-risk medulloblastoma. The appropriate dose of
      radiation to the craniospinal axis when this modality is combined with
      chemotherapy for low-risk medulloblastoma remains to be defined. Long-term
      results of hyperfractionated radiation therapy are likewise awaited. In an effort
      to decrease late toxicity to the immature central nervous system, radiation
      therapy can be delayed in a proportion of infants by administering chemotherapy
      after maximal tumor debulking.

PMID- 9189940
TI  - Clinical trials referral resource. Clinical trials in elderly patients.

PMID- 9189941
TI  - Current challenges of gene therapy for prostate cancer.
AB  - Gene therapy for prostate cancer faces hurdles similar to those being encountered
      for other cancers and nonmalignant processes. The greatest obstacle is the
      identification of efficient delivery systems, since numerous animal models and
      cell culture systems have shown potential efficacy when most cells express the
      introduced genetic material. Early prostate cancers are easily accessible to gene
      vector introduction, and the predictable metastatic patterns of this cancer may
      offer additional advantages for gene therapy. This article reviews gene vectors
      and gene products, as well as ongoing trials of gene therapy that have recently
      begun in prostate cancer.

PMID- 9189942
TI  - Breast cancer surgical practice guidelines. Society of Surgical Oncology practice
      guidelines.

PMID- 9189944
TI  - Ovarian cancer surgical practice guidelines. Society of Surgical Oncology
      practice guidelines.

PMID- 9189943
TI  - Lung cancer surgical practice guidelines. Society of Surgical Oncology practice
      guidelines.

PMID- 9189945
TI  - Prostate cancer surgical practice guidelines. Society of Surgical Oncology
      practice guidelines.

PMID- 9189946
TI  - Anti-HIV effects of Viracept persist during long periods of combination therapy.

PMID- 9189947
TI  - "Comanagement": a word used to hide collusion.

PMID- 9189949
TI  - A full-thickness scleral graft for the surgical management of a late filtration
      bleb leak.
AB  - BACKGROUND AND OBJECTIVES: Late bleb leak may follow months to years after
      filtration surgery. This article describes the surgical repair of eight leaking
      blebs using a full-thickness scleral graft and analyzes the efficacy of the
      procedure and its effect on intraocular pressure (IOP) control. PATIENTS AND
      METHODS: The indications for surgical bleb revision were hypotony maculopathy (2
      eyes), endophthalmitis (2 eyes), bleb infection (2 eyes), and chronic epiphora
      and blurring of vision (2 eyes). All eyes were treated surgically through bleb
      excision and repair of the scleral defect with a full-thickness scleral graft.
      Conjunctival closure was performed either by its advancement to the limbus or by
      free conjunctival autograft. Follow-up ranged from 4 months to 7 years. RESULTS:
      Surgery stopped the leak in all cases, and hypotony was relieved without loss of
      long-term IOP control. However, early postoperative IOP rises (> 30 mm Hg)
      occurred in 2 eyes and a pressure-lowering medication was necessary to achieve
      long-term IOP control (IOP < 22 mm Hg) in 3 eyes. CONCLUSIONS: The technique
      described is an effective procedure for the treatment of late bleb leaks and is
      especially useful for the treatment of leaks found in association with full
      thickness scleral defects. IOP spikes in the early postoperative period may
      occur, but long-term IOP control can be expected without the need for further
      filtration surgery.

PMID- 9189948
TI  - Bleb infections: clinically different courses of "blebitis" and endophthalmitis.
AB  - BACKGROUND AND OBJECTIVES: To assess the differences in history, clinical course,
      and response between five cases of blebitis and three cases of endophthalmitis
      following mitomycin trabeculectomy. PATIENTS AND METHODS: The authors conducted a
      retrospective review of eight consecutive cases of bleb-related infection
      following successful mitomycin trabeculectomy. RESULTS: All patients with
      blebitis responded to treatment with return of visual acuity and intraocular
      pressure to preinfection levels. In the three cases of endophthalmitis, one
      patient underwent enucleation, one had a final visual acuity of counting fingers,
      and the third had a visual acuity of 20/60. CONCLUSIONS: Blebitis, a limited form
      of bleb-related infection with thin, cystic, leaky blebs, responds to intensive
      topical antibiotic treatment, returning visual acuity and IOP to preinfection
      levels. Bleb-related endophthalmitis causes a more virulent form of bleb-related
      infection that involves thin- or thick-walled blebs, with or without leakage, and
      poor visual prognosis despite immediate intensive topical, systemic, and
      intravitreal antibiotic administration combined with core vitrectomy.

PMID- 9189950
TI  - Phacoemulsification with and without trabeculectomy in patients with glaucoma.
AB  - BACKGROUND AND OBJECTIVE: This retrospective study was performed to determine the
      postoperative intraocular pressure (IOP) control in patients with glaucoma who
      underwent phacoemulsification with and without trabeculectomy. PATIENTS AND
      METHODS: Thirty-five eyes underwent phacoemulsification, and 21 eyes underwent
      combined surgery. The minimum postoperative follow-up for both groups was 6
      months. RESULTS: The average IOP decreased from 19.7 +/- 4.6 mm Hg preoperatively
      to 16.3 +/- 3.1 mm Hg in the phacoemulsification group, and from 21.2 +/- 5.9 mm
      Hg to 14.4 +/- 3.3 mm Hg in the combined group at 6 months (statistically not
      significant). There was no statistically significant difference between the
      groups in terms of visual acuity improvement or the number of glaucoma
      medications. CONCLUSION: Cataract surgery, with phacoemulsification alone and
      combined with trabeculectomy, induces a statistically and clinically significant
      reduction of IOP in patients with glaucoma.

PMID- 9189951
TI  - Risk factors for unsatisfactory intraocular pressure control in combined
      trabeculectomy and cataract surgery.
AB  - BACKGROUND AND OBJECTIVE: Trabeculectomy combined with posterior chamber
      intraocular lens (PC IOL) insertion is often chosen for the treatment of glaucoma
      combined with cataract. In this study, the clinical prognostic indicators for
      late intraocular pressure (IOP) control in combined procedures were investigated.
      PATIENTS AND METHODS: The clinical records of 60 eyes that underwent
      trabeculectomy combined with PC IOL implantation were retrospectively analyzed
      using the Cox proportional hazards model. All of the patients received
      postoperative 5-fluorouracil injections. RESULTS: Extracapsular cataract
      extraction (ECCE) was found to be a statistically significant risk factor for
      unsatisfactory late IOP control (hazard ratio 2.54; P < .01) and for
      unsatisfactory filtering bleb appearance (hazard ratio 5; P < .001). The
      frequency of fibrin formation and the incidence of a transient IOP spike (> or =
      25 mm Hg) were significantly lower in the phacoemulsification and aspiration
      (PEA) group than in the ECCE group. In the PEA group, the probability of IOP
      control (< or = 15 mm Hg) without medication was 54%, and the probability of
      persistent filtering bleb appearance was 80% at 18 months. CONCLUSION: The PEA
      technique, not ECCE, should be employed in combined trabeculectomy and PC IOL
      implantation.

PMID- 9189952
TI  - Transscleral ciliary body photodynamic therapy using phthalocyanine and a diode
      laser: functional and morphologic implications in albino rabbits.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the morphologic and functional effects of
      ciliary body photodynamic therapy (PDT) using phthalocyanine and a diode laser.
      MATERIALS AND METHODS: The upper half of the left eye ciliary body of 16 albino
      rabbits was irradiated transsclerally using a 670-nm diode laser (400 mW/cm2)
      after intravenous injection of phthalocyanine (6 mg/kg). The animals were
      observed for a maximum of 2 months by means of tonometry, biomicroscopy, and
      fundus examination. At the end of the follow-up period, they were killed and
      their eyes were prepared for light and electron microscopy. RESULTS: Transscleral
      PDT resulted in intraocular pressure (IOP) reduction in the treated eye, which
      lasted about 2 weeks. During this time, the treated eye had IOP values that were
      significantly lower than its baseline IOP values and the IOP values of the
      untreated eye (P < .05). One month after the procedure, the IOP had returned to
      baseline values. Histologic examination revealed vascular endothelial cell damage
      causing vascular thrombosis in the treated areas. The architecture of the two
      ciliary epithelium layers showed a significant abnormality. Disappearance of
      epithelial apical junction complexes and loss of the normal b-cytomembrane
      enfolding were observed in the course of electron microscopic examination. Large
      intercellular spaces between epithelial cells were noticed. All of these changes
      had subsided by the end of the second postoperative month. CONCLUSION:
      Transscleral phthalocyanine-mediated PDT with the parameters used in this
      experiment results in significant but temporary functional and morphologic
      alterations in the ciliary bodies of albino rabbits.

PMID- 9189953
TI  - Transscleral diode laser cyclophotocoagulation on autopsy eyes with abnormally
      thinned sclera.
AB  - BACKGROUND AND OBJECTIVE: To determine, using autopsy eyes, whether diode laser
      energy adjustments are indicated in patients with thin sclera. MATERIALS AND
      METHODS: In the laboratory, the superior 180 degrees of sclera at the limbus was
      dissected to the level of barely visible anterior uvea and the opposite 180
      degrees of sclera served as the control in three human cadaver eyes. A contact G
      probe was placed at the limbus, and settings of a diode laser were increased in
      increments from 1.0 to 9.0 J at 4 burns per setting in each location. RESULTS: On
      gross examination, circular hypopigmented lesions were seen in the ciliary body
      (CB) beginning at 3.0 J in thin sclera and at 5.0 J in normal sclera. On light
      microscopic examination of thin scleral sections, CB damage began at 2.9 J and
      CB/ciliary body epithelium (CBE) damage occurred beginning at 3.5 J. In normal
      sclera, minimal CB/CBE changes occurred at 6.0 to 7.5 J. No scleral damage was
      visible in either the experimental or the control groups. CONCLUSION:
      Cycloablation energy adjustments are indicated on eyes with abnormally thin
      sclera to achieve similar histologic end points using the diode laser.

PMID- 9189954
TI  - Malignant melanoma of the lacrimal sac complicating primary acquired melanosis of
      the conjunctiva.
AB  - An 81-year-old woman with primary acquired melanosis of the conjunctiva had
      multinodular invasive malignant melanoma, with one nodule engulfing the superior
      lacrimal punctum. At exenteration, the lacrimal sac was noted to be involved with
      melanoma, and an en bloc resection of the orbital contents along with the medial
      orbital wall and the medial wall of the maxillary antrum was performed to excise
      the lacrimal drainage apparatus. In situ melanoma was found in the superior
      canaliculus with invasive melanoma in the lacrimal sac. In situ melanoma was also
      found in the ductules of the lacrimal gland and the accessory lacrimal glands of
      the fornix. The patient died 8 months later of metastatic melanoma. The
      involvement of the lacrimal drainage apparatus by primary acquired melanosis or
      in situ melanoma makes clinical monitoring and management difficult.

PMID- 9189955
TI  - Hypopyon uveitis following panretinal photocoagulation.
AB  - The authors describe the rare complication of hypopyon uveitis following
      panretinal photocoagulation. A 55-year-old man with a history of diabetes
      mellitus and previous repair of a retinal detachment by scleral buckle and
      vitrectomy was referred to the authors after a hypopyon uveitis developed
      following supplemental panretinal photocoagulation. The patient was treated with
      frequent topical steroids in addition to periocular injection of steroids with
      resolution of the inflammation. Risk factors for anterior segment ischemia, such
      as a history of a scleral buckle, may predispose diabetic patients to the
      complication of hypopyon uveitis following panretinal photocoagulation.

PMID- 9189956
TI  - Utilizing gravity in the removal of a large intraocular foreign body.
AB  - This article describes an unconventional technique for the removal of a
      nonmagnetic intraocular foreign body that is too large or too smooth to be
      grasped by intraocular forceps and does not float on perfluorocarbon liquids. By
      flipping the patient to a face-down position and allowing the gravitational
      forces to help remove the object, one can hope to avoid further ocular damage.
      This approach should be considered in similar cases of very large and smooth
      intravitreal foreign bodies to avoid severe and irreversible damage to the
      retina.

PMID- 9189957
TI  - Surgical reconstruction for angle-closure glaucoma due to a flat anterior chamber
      following trabeculectomy.
AB  - In cases in which filtration surgery such as trabeculectomy is necessary, a flat
      anterior chamber postoperatively due to overfiltration may cause severe problems
      in the control of intraocular pressure. Once a broad synechia has formed between
      the iris and the corneal endothelium, this type of refractory, surgically induced
      angle closure can be difficult to manage. This article details a case of
      refractory angle-closure glaucoma secondary to a flat anterior chamber following
      trabeculectomy. Multiple surgical treatments were performed to control
      intraocular pressure and to reconstruct the anterior segment of the eye.

PMID- 9189958
TI  - An intraocular telescopic lens for macular degeneration.
AB  - Age-related macular degeneration is a leading cause of visual loss in adults
      older than 60 years of age. Once vision has been seriously compromised, the only
      means of improving visual function are optical devices that produce magnification
      of images. These devices fall into three categories: (1) high-plus lenses, (2)
      external telescopes, and (3) a high-minus center intraocular lens combined with
      external high-plus glasses. The authors designed a new intraocular lens with an
      entire telescope in its center. In vitro tests were performed to evaluate
      modulation transfer function, visual field, and optical aberrations. Implantation
      in cadaver eyes was performed to test the surgical technique and safety. Test
      results showed that satisfactory modulation transfer function and optic
      aberration were achieved, and implantation in cadaver eyes was proven to be
      feasible and safe. It was concluded that a fully implanted intraocular telescopic
      lens is an effective optical solution for age-related macular degeneration.

PMID- 9189959
TI  - A motorized hand piece for injectable lenses.
AB  - Foldable lenses represent a major breakthrough in the effort to achieve ever
      smaller incisions. The plate-haptic or "taco-style" lenses are folded and
      implanted by a device called an injector. Although customized for each
      manufacturer's lens, the injectors all have a common design principle: the
      intraocular lens (IOL) is folded within a funnel-like structure of the tip and is
      advanced by a plunger that pushes and delivers the lens. To maintain optimal hand
      stabilization and injector management, both hands are usually required. This does
      not leave a hand to help with IOL positioning. To improve handling, a simple,
      mechanized system has been created for a new injector system that allows the
      delivery of the plate-haptic lens with one hand, in a pen-like fashion.

PMID- 9189960
TI  - "Pneumofornix" (air under the eyelid): a normal finding.
AB  - Normal pockets of air under the eyelids have not been previously described in the
      literature. To assess the incidence and patterns of normal air bubbles in the
      region of the eyelid, computed tomography (CT) scans of 126 normal orbits and 36
      orbits of patients with thyroid orbitopathy were assessed. Twenty-eight (22%) of
      the normal orbits and 14 (39%) of the thyroid orbits had a well-defined medial or
      lateral air bubble (or both) on axial views (.1 > P > .05). Oval central or
      paracentral air bubbles in sections through the superior or inferior fornix were
      seen in 19 (15%) of the normal orbits and 10 (28%) of the thyroid orbits (.1 > P
      > .05). It is important to be aware of the incidence and patterns of these normal
      air bubbles to ensure their accurate differentiation from pathologic air bubbles.

PMID- 9189961
TI  - Blood saving in paediatric anaesthesia.

PMID- 9189962
TI  - Mivacurium in infants and children.
AB  - Mivacurium is the only available short-acting nondepolarizing muscle relaxant in
      clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by
      plasma-cholinesterase into inactive compounds. The ED50 and ED95 in children are
      about 50 micrograms.kg-1 and 90 micrograms.kg-1 respectively. In infants, they
      have a tendency to be lower. A standard intubating dose of 0.25 mg.kg-1 causes
      complete neuromuscular depression in 1.5-2 min, recovery to 5% in 6-10 min, and
      complete recovery in 15-20 min. The recent tendency is to use 0.3 mg.kg-1 to
      obtain better intubating conditions with slight prolongation of effect. Since the
      recovery profile of mivacurium is independent of the dose and duration, it is
      most suitable for administration by continuous infusion. The infusion requirement
      in children is 10-16 micrograms.kg-1 min-1, which is about twice that of adults.
      Cutaneous flushes from histamine release are commonly seen with the larger doses
      of mivacurium; however, the associated hypotensive effects are minimal and
      counteracted by the tracheal intubation. The duration of action of mivacurium is
      prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular
      effects can be satisfactorily antagonized by edrophonium or neostigmine.

PMID- 9189963
TI  - Oral premedication with midazolam in paediatric anaesthesia. Effects on sedation
      and gastric contents.
AB  - The aim of this study was to assess oral premedication with midazolam in
      paediatric anaesthesia. Sedation, quality of induction, recovery time, acceptance
      and effects on gastric contents were analysed. This prospective, double blind, at
      random and controlled study was performed in 107 children, aged between three and
      ten years. They were divided into: group 1 (control, n = 29), group 2 (placebo)
      receiving 5 ml of water in the preoperative stage (n = 40), and group 3
      (midazolam) with 0.75 mg.kg-1 midazolam by mouth (n = 38). Two children refused
      to take medication. In children aged five years or more (n = 48) of groups 2 and
      3, acceptance of premedication was evaluated. The midazolam group showed a better
      level of sedation as compared with the placebo (P < 0.05). The recovery time was
      similar for the two groups. There were no statistically significant differences
      in gastric pH or residual volume among the three groups. It is concluded that
      midazolam given by mouth is an efficient and safe drug for premedication in
      paediatric anaesthesia.

PMID- 9189964
TI  - Global tissue oxygenation during normovolaemic haemodilution in young children.
AB  - Sixteen patients (1-8 years) scheduled for major general surgery were chosen for
      the study. They were divided into two groups according to the replacement
      solution used for haemodilution (HD); whether 6% middle molecular weight
      hydroxyethyl starch (HES) or 6% dextran 60 (DEX). After induction of general
      anaesthesia and pulmonary artery catheterization, a precalculated amount of
      autologous blood was withdrawn while the patient's autologous blood was
      simultaneously replaced by either HES or DEX. Autologous blood was retransfused
      at a minimum haematocrit (Hct.) of 17% or at the end of surgery. The following
      parameters were measured and/or calculated before and after HD, every 20 min
      intraoperatively and hourly for 6 h postoperatively: heart rate (HR), mean
      arterial pressure (MAP), Cardiac index (CI), Hct., arterial and mixed venous
      oxygen content (CaO2, CvO2) and arterio-venous difference of oxygen content
      (avDO2), oxygen delivery index (DO2I), oxygen consumption index (VO2I). The
      cardiovascular system remained stable. There was no significant difference as
      regards SvO2, despite a significant decrease in CaO2 to 10.8 and 10.0 ml.dl-1
      (median values) due to reduction of haemoglobin concentration in the HES and DEX
      groups respectively. In spite of the low hct. values during surgery DO2I remained
      in normal range (median value 602 and 710 ml.min-1.m-2) in HEX and DEX group
      respectively. There was no significant change in VO2I after haemodilution (median
      value 212 and 243 ml.min-1.m-2) in either group. No statistically significant
      difference was noticed between either groups regarding: CaO2, CvO2, DO2I, VO2I,
      and no side effects of the colloids were observed. Isovolaemic haemodilution
      (Hct. approximately 17%) is well tolerated by young children undergoing major
      elective surgery; global tissue oxygenation was preserved throughout the
      procedure and both solutions used for haemodilution were equally effective.

PMID- 9189965
TI  - High spinal anaesthesia for repair of patent ductus arteriosus in neonates.
AB  - General anaesthesia with high dose narcotics has traditionally been used for
      repair of patent ductus arteriosus (PDA) in high risk neonates. Spinal
      anaesthesia in infants has generally been limited to cases involving the lower
      abdomen and lower extremities. Regional anaesthesia for PDA repair could
      potentially offer a more rapid recovery and the possibility of blunting the
      stress response in this vulnerable group of patients. High spinal anaesthesia
      with tetracaine was utilized as an alternative to general anaesthesia in a series
      of fifteen consecutive patients. Patient demographics, medication dosages, level
      of anaesthesia, intraoperative and immediate postoperative data were obtained and
      recorded in a prospective fashion. Spinal anaesthesia was achieved in all
      patients. The average dose of tetracaine was 2.4 mg.kg-1. Two patients early in
      the series had an inadequate level and received supplemental isoflurane. The
      remainder of the patients received either no or minimal supplementation to the
      basic technique. Cardiovascular status of the group was very stable with minimal
      changes in blood pressure noted. Recovery was rapid. All three patients who were
      not intubated at the time of surgery were extubated soon after surgical repair
      was completed. No complications of the technique were noted. High spinal
      anaesthesia is a safe and effective alternative to general anaesthesia in high
      risk neonates. This technique may offer the advantage of a faster recovery time
      and a protective effect on the neonatal stress response. In addition the
      stability of this technique may encourage the use of higher levels of spinal
      anaesthesia in infants than has traditionally been used.

PMID- 9189966
TI  - Para-umbilical block: a new concept for regional anaesthesia in children.
AB  - This preliminary study describes a new technique to provide analgesia in children
      undergoing umbilical hernia repair. The para-umbilical block consists of
      infiltrating the anterior cutaneous branches of the two tenth spinal roots over
      and under the rectus sheath far from the operative field. Intra and postoperative
      analgesia as well as operative conditions were assessed in 11 children 16.7 +/-
      31 months old, weighing 8421 +/- 6941 g, the block being performed before surgery
      under light general anaesthesia. Intraoperative analgesia, operative conditions
      and recovery were good in all patients. Analgesia was adequate one h after
      surgery in ten patients, six h after surgery in eight. The block proved to be
      safe and on the whole effective in this short series. The study should proceed on
      a multi-centre basis if possible. Indications can be extended.

PMID- 9189967
TI  - Video-assisted thoracoscopic surgery for right middle lobectomy in children.
AB  - This case-control study was designed to evaluate the potential advantages and
      disadvantages of video-assisted thoracoscopic surgery for right middle lobectomy
      in children. Ten children (6.1 +/- 3.0 yr, mean +/- SD) who underwent right
      middle lobectomy under videoscopy were compared with 10 controls matched for age
      (6.8 +/- 3.5 yr) and operated by thoracotomy (muscle-sparing technique) during
      the same period by the same surgeon. Operating time was significantly longer in
      the videoscopy group than in the thoracotomy group (146 +/- 28 mn vs 100 +/- 27
      mn, P < 0.001). Minimum oxygen saturation values were significantly higher in the
      videoscopy group whereas oxygen requirements did not differ between groups.
      Incidence of postoperative respiratory complications (mainly atelectasis) was
      similar in the two groups. No difference in postoperative analgesic requirements
      in the postoperative period was demonstrated. No real benefit or disadvantage of
      videoscopy over standard thoracotomy could be observed in this retrospective case
      control study.

PMID- 9189968
TI  - Diclofenac vs oxybuprocaine eyedrops for analgesia in paediatric strabismus
      surgery.
AB  - Forty children undergoing strabismus surgery as day patients were randomly
      allocated to receive oxybuprocaine 0.4% eyedrops or 0.1% diclofenac eyedrops for
      perioperative analgesia. A non-invasive anaesthetic technique using the
      reinforced laryngeal mask airway was used. The study demonstrated that both
      topical analgesics provided good to excellent analgesia and the anaesthetic
      technique was associated with a relatively low incidence of nausea and vomiting.
      Complications were limited to two children who were admitted with persistent
      postoperative nausea and vomiting.

PMID- 9189969
TI  - Pain and activity disturbance after paediatric day case adenoidectomy.
AB  - Over the past two decades outpatient surgery has become standard practice in
      paediatric surgery. Adenoidectomy is a common surgical procedure in children. In
      this prospective survey pain and pain-related outcomes such as sleep and activity
      disturbance were evaluated in 167 children aged 1-7 years who had undergone
      adenoidectomy as a day case in Kuopio University Hospital. The survey
      questionnaire consisted of 76 structured questions about pain, pain medication,
      adverse effects and daily activities during first week after the operation.
      Eighty-three per cent of children had pain at home and 17% of them had moderate
      or severe pain on a four point verbal rating scale. Eighty per cent of children
      used pain medication at home. Pain medication did not cause any major adverse
      effects. Over 90% of children were back to normal daily activities during the
      first three postoperative days and nearly all were able to drink during the whole
      postoperative period. We conclude that pain is a common problem after
      adenoidectomy in children but most of the children return to normal activities
      within three days.

PMID- 9189970
TI  - A simple homemade lighted stylet for neonates and infants: a description and case
      report of its use in an infant with the Pierre Robin anomalad.
AB  - The glossoptosis and micrognathia associated with Pierre Robin anomalad can make
      tracheal intubation by conventional laryngoscopy quite difficult. Lighted stylets
      may be helpful in the successful intubation of infants with this anomalad, but
      those currently available that are small enough to accommodate 3.0 mm ID tracheal
      tubes have two major drawbacks limiting their utility: an insufficiently rigid
      stylet component and a nonadjustable, overly bright light. We describe a lighted
      stylet that can be easily assembled in the operating room which overcomes these
      problems and allowed us to successfully intubate a six-day-old with severe Pierre
      Robin anomalad.

PMID- 9189971
TI  - Perioperative considerations in a newly described subtype of congenital long QT
      syndrome.
AB  - An infant with a newly-described subtype of congenital long QT syndrome is
      presented, along with her perioperative management on three separate occasions.
      During each anaesthetic characteristic arrhythmias occurred. The available
      literature and rational approaches to these high risk patients are reviewed.

PMID- 9189972
TI  - Massive blood loss during tonsillectomy in a child with congenital venous
      malformation.
AB  - Tonsillectomy and adenoidectomy have become frequently performed outpatient
      procedures and are generally considered to have a low morbidity profile.
      Postoperative haemorrhage remains a rare but important complication, while
      intraoperative uncontrollable bleeding is extremely uncommon. A child with
      congenital vascular malformation of the lip and oropharynx undergoing
      tonsillectomy experienced massive blood loss, subsequent resuscitation and
      significant perioperative morbidity including a prolonged intensive care unit
      stay. Preoperative/preanaesthetic nasopharyngoscopic exam and magnetic resonance
      imaging did not reveal vascular prominence of the tonsils. Preoperative
      consideration of angiography or magnetic resonance angiography may be prudent to
      avoid this potentially fatal complication.

PMID- 9189973
TI  - Major limb deformities as complications of vascular access in neonates.
AB  - Four case histories are used to illustrate orthopaedic complications of vascular
      access in neonates. The two main pathologies, extravasation and thrombosis, are
      discussed and the management of each outlined. Mechanisms of avoidance of such
      complications are described and advocated.

PMID- 9189974
TI  - Anaesthetic management of children with Joubert syndrome.
AB  - We report the anaesthetic management of two children with Joubert syndrome.
      Children with this syndrome have abnormalities of respiratory control due to
      changes in the brainstem and cerebellum. They are extremely sensitive to the
      respiratory depressant effects of anaesthetic agents, including nitrous oxide.
      Anaesthesia using inhalational induction, controlled ventilation, avoidance of
      opioids, and close postoperative monitoring is recommended.

PMID- 9189975
TI  - Repair of ventricular septal defect in a child with severe pulmonary hypertension
      -response to inhaled nitric oxide.
AB  - Nitric oxide (NO), was administered successfully, to a child with severe
      pulmonary hypertension, following surgical repair of a large ventricular septal
      defect. Inhalation of NO, 20-25 parts per million (ppm) was continued for 24 h,
      resulting in mean pulmonary artery pressure (PAP) of 25 mmHg and permitting a
      reduction in both ventilatory and inotropic support. Weaning of NO was commenced.
      At 5 ppm, administration was discontinued. An immediate and dramatic increase in
      PAP occurred. A similar pattern resulted on further attempts, demonstrating the
      extreme sensitivity of the pulmonary vasculature to the effects of inhaled low
      dose NO and the selectivity of the response.

PMID- 9189976
TI  - Prevention of venous air embolism by jugular venous compression under superior
      sagittal sinus pressure monitoring in a brachycephalic patient during
      craniofacial reconstruction.

PMID- 9189977
TI  - Deep sedation with propofol for paediatric radiotherapy.

PMID- 9189978
TI  - Intrathecal morphine for a child with bronchopulmonary dysplasia.

PMID- 9189979
TI  - Parent-assisted anaesthesia.

PMID- 9189981
TI  - Differential age-related processing limitations in recall and recognition tasks.
AB  - The degree to which processing resources are responsible for age differences in
      performance on recall and recognition tasks was examined in this study. To
      examine this, a secondary task incorporating a memory component (digit preloads)
      was implemented during retrieval. Results revealed that older adults, relative to
      younger adults, exhibited greater decrements in secondary task performance as the
      difficulty of the secondary task increased. These age differences were greater in
      the recall task than in the recognition task. Hierarchical regression analyses
      indicated that speed accounted for the largest proportion of age-related variance
      in the recall task while both speed and working memory contributed to much of the
      secondary task variance. Results confirm the hypothesis that recall requires
      greater processing capacity than recognition and that older adults have greater
      processing-capacity limitations than younger adults.

PMID- 9189980
TI  - False recollection induced by photographs: a comparison of older and younger
      adults.
AB  - Looking at photographs constitutes an important everyday memory activity for
      older adults. The authors found that reviewing photographs of events seen earlier
      in a videotape increases the likelihood that both older and younger adults
      remember specific details from the reviewed event (W. Koutstaal, D. L. Schacter,
      M. K. Johnson, K. E. Angell, & M. S. Gross, 1977). In the present study, the
      authors report 2 experiments demonstrating that photo review can also produce
      false recollection in elderly adults: After reviewing photos of events that had
      not been shown earlier in a videotape, older but not younger adults were later
      more likely to "remember" that those events had been shown in the videotape.
      False recollection induced by photo review appears to reflect an age-related
      deficit in source-monitoring abilities.

PMID- 9189982
TI  - Aging or disease? Cardiovascular reactivity in Finnish men over the middle years.
AB  - Cardiovascular responses to psychological events may mediate the influence of
      stress on cardiovascular disease. In this study the authors asked whether
      cardiovascular responses to psychological challenge changed with age and whether
      such changes were intrinsic to aging or could be attributed to the influence of
      disease and medications. Cardiovascular reactivity to mental challenge was
      examined in 902 men ranging in age from 46 to 64 years who participated in the
      Kuopio Ischemic Heart Disease Risk Factor Study. A battery of 4 tasks was used to
      induce cardiovascular responses. Current disease status, age, and medication use
      were entered into hierarchical regression analyses to assess their relation with
      measures of cardiovascular reactivity. Age and hypertension contributed
      independent, approximately equal, but small amounts of variance in the cardiac
      and vascular reactivity indexes. Medications also influenced reactivity
      independently of age and disease. Performance on the tasks was more consistently
      altered by age than by disease or medication. Cardiac and vascular reactivity
      increased with increasing age and the presence of hypertension. The authors
      conclude that both age and disease state must be considered when examining
      cardiovascular reactivity as a risk factor for disease.

PMID- 9189983
TI  - Psychosocial development and life experiences in adulthood: a 22-year sequential
      study.
AB  - In this study, a model was tested postulating reciprocal relationships between
      psychosocial development and life experiences in adulthood. A sequential design
      compared college alumni (n = 99) who were age 20 in 1966, age 31 in 1977, and 42
      in 1988 (Cohort 1) with college alumni (n = 83) who were 20 in 1977 and 31 in
      1988 (Cohort 2). Path analyses testing specific hypotheses provided partial
      support for the reciprocal model. For Cohort 1 men, lower socioeconomic levels at
      age 31 were associated with higher industry versus inferiority scores at age 42.
      For Cohort 1 women, higher identity scores at the age of 31 predicted full-time
      homemaker status by age 42. The findings from 20 to 31 years were more consistent
      for Cohort 2, with college psychosocial scores predictive of greater success and
      commitment in the areas of occupation and family life. Differences between the
      cohorts were interpreted in terms of sociohistorical factors including
      differential socialization between men and women in the 1960s versus the 1970s,
      as well as peculiarities of the period of the 1960s that appeared to influence
      specifically men who were in college.

PMID- 9189984
TI  - Effects of familiarity of task and choice on the functional performance of
      younger and older adults.
AB  - An experiment was conducted to compare the functional performance of younger and
      older adults on familiar and unfamiliar tasks under 2 conditions of perceived
      control. Specifically, the relation between age and motor and process skills was
      examined. The familiar tasks were simple cooking tasks, whereas the unfamiliar
      tasks were contrived, meaningless tasks developed for this study. Younger and
      older adults did not differ in the ratings of the familiarity of the tasks, but
      results from 2 Age x Task x Choice analyses of variance demonstrated a
      significant age difference for motor and process skills under all conditions.
      This suggests that older adults demonstrate age-related decline, even with
      activities that take motivational, experiential, and ecological validity
      components into account. For the process skills scale, there was also a
      significant main effect for choice. These results support the concept that
      perceived control may improve performance, but not differentially for older
      adults; that is, younger and older adults both demonstrated improved process
      performance when given their choice of tasks.

PMID- 9189985
TI  - State-dependent learning in older and younger adults.
AB  - In this study state-dependent learning in younger and older adults was compared.
      State was manipulated by having participants rest or exercise for 5 min, followed
      by exposure to 3 learning trials of a 20-item word list. After a 20-min delay,
      participants engaged either in the congruent or in the incongruent activity
      followed by free-recall trial, cued-recall, and recognition tests. Heart rate,
      blood pressure, and self-report of distress measures verified that the
      experimental conditions influenced the participants' physiologic state, but the
      distracter tasks did not. There was no difference in learning that was due to
      initial exercise condition, but both age groups showed greater recall when state
      was congruent before learning and delayed recall. This replicates previous
      research in which consistent state-dependent learning effects in younger adults
      were found and supports research suggesting that older adults spontaneously use
      contextual information to facilitate recall. The demonstration of state-dependent
      learning in older adults is discussed as an example of implicit memory not
      affected by aging.

PMID- 9189986
TI  - Patterns of coping preferences for male and female caregivers of frail older
      adults.
AB  - The similarities and differences in male and female caregivers' preferred
      strategies for coping and the perceived helpfulness of these strategies in
      managing caregiving stressors were examined in this study. Respondents were 170
      caregivers (139 women and 31 men) who were primary caregivers for an elderly
      adult relative who was either cognitively impaired or physically frail. Results
      provide preliminary evidence that gender is related to frequency of use but not
      to the perceived helpfulness of specific coping strategies.

PMID- 9189987
TI  - A comparison of the factor structure of processing speed for younger and older
      adults: testing the assumption of measurement equivalence across age groups.
AB  - The purpose of this study was to investigate measurement equivalence of
      processing speed measures for different age groups. A structural equation
      modeling approach was used to investigate a measurement model and the factorial
      invariance between younger and older adults on speed measures. The analyses
      concurrently examined whether speed-related abilities dedifferentiate with
      increasing age. One hundred and forty-four younger and 105 older adults completed
      9 measures designed to assess motor speed, alphanumeric speed, and geometric
      speed. Results indicated that although the number of factors and the factor
      loadings were invariant across age groups, the interfactor correlations, the
      variance-covariance matrices, and the unique variances differed across groups.
      Furthermore, a second-order speed factor seemed to explain much of the variance
      in the 3 first-order factors, although this higher order factor accounted for
      slightly more variance among the older group than among the younger group. The
      results suggest that there is sufficient evidence of measurement equivalence on
      the current speed measures across the 2 adult age groups and, in addition,
      provide evidence of dedifferentiation.

PMID- 9189988
TI  - Center for Epidemiologic Studies Depression Scale (CES-D) as a screening
      instrument for depression among community-residing older adults.
AB  - The efficacy of the Center for Epidemiologic Studies Depression Scale (CES-D) as
      a screener for clinical depression was examined in a sample of 1,005 community
      residing adults (age range = 50-96). Presence of a depressive disorder was
      determined by diagnostic interview. Analyses revealed that neither age, gender,
      cognitive impairment, functional impairment, physical disease, nor social
      desirability had a significant negative effect on the psychometric properties or
      screening efficacy of the CES-D. These results indicate that there was no
      significant degradation in the ability of the CES-D to screen for depression
      among community-residing elderly adults. This conclusion must be tempered by the
      fact that the sample did not include participants with the more disabling forms
      of cognitive or functional impairment and physical illness.

PMID- 9189989
TI  - Distinctive late-life challenges: implications for coping and well-being.
AB  - Two distinctive late-life challenges, community relocation and caring for an
      adult child with mental retardation, were studied to determine their influence on
      coping and well-being. These challenges differ in terms of their normativeness,
      duration, and whether they were expected. Data from 2 ongoing longitudinal
      studies (N = 449) were used to test the hypotheses that women experiencing
      residential relocation would report higher well-being and use problem-focused
      coping more frequently than women with long-term caregiving responsibilities. As
      predicted, more positive changes in well-being across time were reported by the
      relocation sample, which also showed more problem-focused coping. Women in the
      caregiving sample, however, showed stronger relationships between coping and well
      being, underscoring possible gains in expertise that accompany challenges of
      lengthy duration.

PMID- 9189990
TI  - Mental illness in late life: socioeconomic conditions, psychiatric symptoms, and
      adjustment of long-term sufferers.
AB  - The relationships between social and economic conditions and psychiatric disorder
      among 346 older adults with severe mental illness living in the community are
      examined in this article. Measures included socioeconomic indexes, symptoms,
      diagnoses, and adjustment. As expected, socioeconomic and illness factors were
      interrelated in this sample. Diagnosis was related to both functioning and
      socioeconomic factors. As a rule, participants were financially impoverished but
      socially integrated into social networks consisting largely of kin. In spite of
      impoverishment and presence of significant symptoms, most were maintaining
      themselves in the community with at least marginal functioning, though they
      received very little support from the mental health system beyond medication.
      Compared with the younger cohort, the older cohort was functioning better, had
      fewer symptoms, and had better global adjustment. Those with coexisting psychotic
      and affective syndromes were most at risk. Future analyses with this data set
      will need to develop complex multivariate models to predict the primary
      influences on functioning and short-term stability.

PMID- 9189991
TI  - Cognitive correlates of mortality: evidence from a population-based sample of
      very old adults.
AB  - The authors examined performance on memory, visuospatial, and verbal tasks and
      subsequent mortality in adults 75-95 years. The sample consisted of 178 living
      and 44 deceased participants. Mean-level analyses revealed mortality group
      differences for all domains of cognitive functioning. A Cox regression analysis,
      independent of age, gender, education, functional ability, and chronic illness,
      indicated that measures of word recognition and category fluency were significant
      predictors of mortality status. The results indicate a relationship between
      cognitive performance and subsequent mortality status in very old age and suggest
      that episodic memory and verbal skill may be particularly sensitive in predicting
      such effects.

PMID- 9189992
TI  - Effect of age on event-based and time-based prospective memory.
AB  - The magnitude of age differences on event- and time-based prospective memory
      tasks was investigated in 2 experiments. Participants performed a working memory
      task and were also required to perform either an event- or time-based prospective
      action. Control participants performed either the working memory task only or the
      prospective memory task only. Results yielded age differences on both prospective
      tasks. The age effect was particularly marked on the time-based task. Performance
      of the event-based prospective task, however, had a higher cost to performance on
      the concurrent working memory task than the time-based task did, suggesting that
      event-based responding has a substantial attentional requirement. The older
      adults also made a significant number of time-monitoring errors when time
      monitoring was their sole task. This suggests that some time-based prospective
      memory deficits in older adults are due to a fundamental deficit in time
      monitoring rather than to prospective memory.

PMID- 9189993
TI  - Structure and variation of mood in individuals with Parkinson's disease: a
      dynamic factor analysis.
AB  - Mood structure was examined among individuals diagnosed with Parkinson's disease.
      Twelve individuals completed a measure of positive and negative affect for 70
      consecutive days. Mood structure was determined by using dynamic factor analysis
      (DFA) models that account for both concurrent and lagged relationships in
      repeated measurements. Five individuals had sufficient variability in positive
      and negative affect to conduct DFA on both sets of variables. Results showed the
      presence of 2 2-factor 1-lag models, 2 1-factor 1-lag models, and a P-technique
      model. There was sufficient variability in positive affect to conduct DFA on
      positive affect for the entire sample. Two individuals displayed 2-factor 1-lag
      models, 6 individuals had 1-factor 1-lag models, and 4 individuals showed P
      technique models. Implications of lagged relationships are discussed from
      substantive and methodological perspectives.

PMID- 9189994
TI  - Predicting episodic memory performance of very old men and women: contributions
      from age, depression, activity, cognitive ability, and speed.
AB  - Regression models were developed to explain age-related and total variance in
      memory and to determine the independent contribution from general processing
      speed, having taken into account cognitive and noncognitive individual
      differences. Episodic memory was assessed for 3 tasks in a population-based
      sample of 951 adults comprising 515 men and 436 women (aged 70-96, M = 77.6, SD =
      5.5). Correlations between age and memory accounted for 6%-9% of the variance.
      Hierarchical multiple regressions showed a reduction in this age-related variance
      by up to 94%, after entering gender, depression, health, cognitive status,
      activities, and speed. General processing speed was the major mediator of age
      related variance in memory. Although both the age-related variance and the speed
      related variance in memory were significantly reduced by prior entry of other
      individual differences variables for all 3 tasks, speed remained a significant
      mediator of remembering, and negligible differences in the residual age-related
      variance were observed by inclusion of other background variables.

PMID- 9189995
TI  - An opposition procedure for detecting age-related deficits in recollection:
      telling effects of repetition.
AB  - In 2 experiments, the advantages of placing automatic and consciously controlled
      memory processes in opposition to study age-related declines in memory
      performance were examined. Drawing on the common memory failure of mistakenly
      repeating oneself, a task was designed in which participants had to rely on
      conscious memory (recollection) to avoid repetition errors. Recollection proved
      to be severely affected by aging; older adults showed significantly more
      repetition errors than did younger adults, even at very short retention
      intervals. These results contrast sharply with the small age differences found
      with a standard recognition test. Moreover, L. L. Jacoby's (1991) process
      dissociation procedure (Experiment 2) showed that automatic memory processes were
      unaffected with age and could support recognition performance in older adults.
      The advantages of the opposition procedure for studying memory in older adults
      relative to other measures are discussed.

PMID- 9189996
TI  - Younger and older adults' on-line processing of syntactically ambiguous
      sentences.
AB  - Off-line studies of younger and older adults' processing of syntactically complex
      sentences have shown that there is a consistent negative relationship between
      task performance and working memory for older adults. However, it is not evident
      from these studies whether working memory affects the immediate syntactic
      analysis of a sentence, off-line processes, or both. In the current study an
      online reading paradigm was used to examine the working memory capacity
      constrained sentence processing model from M.C. MacDonald, M.A. Just, and P.A.
      Carpenter (1992). Working memory span, type of syntactic ambiguity (ambiguous vs.
      unambiguous), and type of syntactic ambiguity resolution (main verb vs. relative
      clause) interacted to influence younger and older adults' on-line reading times
      and off-line sentence comprehension.

PMID- 9189997
TI  - Age-related differences in an ecologically based study of route learning.
AB  - Spatial learning abilities in younger adults and in healthy elderly adults were
      examined in 2 tasks. In the first task, participants were tested for their
      ability to recall relevant route information as well as to recognize and to order
      temporally landmark information observed along the route. Older participants had
      relatively greater difficulty retracing the route and temporospatially ordering
      landmarks but were equally good at recognition of landmarks occurring on the
      route. In the second task, participants memorized a 2-dimensional representation
      of a route and subsequently navigated the route from memory. Older participants
      had greater difficulty memorizing the route and navigating it. Errors of
      omission, commission, wrong, and forced choice were analyzed. Group differences
      in the pattern of errors differed by task.

PMID- 9189998
TI  - Stress of parent care: positive and negative effects of women's other roles.
AB  - The present study focused on 296 women who were primary caregivers to an ill or
      disabled parent or parent-in-law and who simultaneously occupied 3 other roles as
      mother, wife, and employee. All women lived in separate households from their
      impaired parent and had at least 1 child 25 years of age or younger living at
      home. It was predicted that stress in the roles of mother, wife, and employee
      would exacerbate the effects of stress in the parent care role on psychological
      well-being (depression and life satisfaction) and that rewards in these 3
      additional roles would buffer the effects of parent care stress. For all 3
      additional roles, findings supported the stress exacerbation hypothesis. In
      contrast, only the employee role supported the stress-buffering hypothesis. These
      findings underscore the complex relationships that often exist between women's
      multiple role experiences and their psychological well-being.

PMID- 9189999
TI  - Thromboangiitis obliterans (Buerger's disease).

PMID- 9190000
TI  - Are drugs helpful in adults with osteogenesis imperfecta?

PMID- 9190001
TI  - Sjogren's syndrome in patients with newly diagnosed untreated non-Hodgkin's
      lymphoma.
AB  - The purpose of the study was to detect cases of Sjogren's syndrome among newly
      diagnosed untreated patients with non-Hodgkin's lymphoma and, furthermore, to
      identify in such cases clinical and serologic features known to occur more
      frequently in Sjogren's syndrome patients who evolve into lymphoma. Accordingly,
      thirty-three cases of newly diagnosed non-Hodgkin's lymphoma, prior to any
      treatment administration, were thoroughly studied for evidence of Sjogren's
      syndrome. Immunophenotyping for T and B cells and kappa and lambda light chains
      was concomitantly performed on both lymphomatous tissues and minor salivary
      glands. There were 5 patients with T cell and 28 with B cell lymphoma of various
      histologic subtypes and grades. Two of the latter (7.1%) had a positive for
      Sjogren's syndrome minor labial salivary gland biopsy, positive responses to the
      specific questionnaires for both eye and mouth dryness and abnormal Schirmer's
      and rose Bengal eye tests, substantiating the diagnosis of Sjogren's syndrome.
      Both were male with lung and stomach non-Hodgkin's lymphoma respectively,
      enlargement of the lacrimal glands, monoclonal gammapathy of the IgM kappa type
      and, one of them had high titer and of fine speckled pattern positive antinuclear
      antibodies and anti-Ro(SSA) and anti-La(SSB) antibodies in his serum. A monotypic
      infiltrate with kappa light chain restriction, identical to that in the
      lymphomatous tissue of these two patients, was present in their minor salivary
      gland biopsy as well. Such a finding was not encountered in any of the remaining
      patients. Although our sample is relatively small, our results confirm the
      relationship between Sjogren's syndrome and non-Hodgkin's lymphoma, looked at
      from the opposite direction. Obviously, studies involving larger populations
      would be more definitive, regarding the issue of what percentage of this lymphoma
      patients originates from Sjogren's syndrome.

PMID- 9190002
TI  - Evaluation of the Amor and ESSG classification criteria for spondylarthropathies
      in a Turkish population.
AB  - This study evaluated the Amor and European Spondylarthropathy Study Group (ESSG)
      classification criteria for spondyloarthropathies in Turkish patients seen from
      October 1990 to August 1993 at the Physical Medicine and Rehabilitation
      Department of the GATA Haydarpasa Training Hospital. The Amor and ESSG criteria
      were evaluated in 157 patients with spondylarthropathies and in 124 controls with
      a variety of other rheumatic diseases. The sensitivity, specificity, positive
      predictive value, and negative predictive value of each criteria set were
      calculated, as well as the sensitivity and specificity of each of the 24 criteria
      used in these sets. For Amor's criteria, sensitivity was 88.5%, specificity was
      91.9%, positive predictive value was 93.3% and negative predictive value was
      86.4%. For the ESSG criteria, sensitivity was 86.6%, specificity was 91.1%,
      positive predictive value was 92.5% and negative predictive value was 84.3%. No
      significant differences were found between the two criteria sets. Our data show
      that the Amor and ESSG criteria are of similar value for the classification of
      spondylarthropathies and are comparable in terms of sensitivity and specificity.
      They also demonstrate the need for monitoring patients with equivocal clinical
      patterns using both sets of criteria as tools that complement each other.

PMID- 9190003
TI  - Prednisolone concentrations in cerebrospinal fluid after oral prednisone.
      Preliminary data.
AB  - Penetration of prednisolone across the blood-brain barrier was studied in 17
      patients (ten women and seven men) with a mean age of 64 +/- 17 years admitted
      for nerve root pain warranting a lumbar puncture. One blood sample and one
      cerebrospinal fluid sample were obtained concomitantly from each patient, two
      hours (n = 7), four hours (n = 5) or six hours (n = 5) after an oral dose of 40
      mg of prednisone. Prednisolone was assayed in all samples using high performance
      liquid chromatography and its binding to plasma proteins was determined using
      ultrafiltration. Total plasma prednisolone levels declined over time from 597 +/-
      174 ng/ml two hours post-dose to 422 +/- 106 ng/ml four hours post-dose and 250
      +/- 85 ng/ml six hours post-dose. Plasma levels of free prednisolone were 95 +/-
      21 ng/ml, 59 +/- 17 ng/ml, and 18 +/- 14 ng/ml, respectively, at the same time
      points. Prednisolone was detectable in all cerebrospinal fluid samples, in levels
      of 14 +/- 2 ng/ml after two hours, 29 +/- 9 ng/ml after four hours and 17 +/- 7
      ng/ml after six hours. These data demonstrate that equilibration of plasma and
      cerebrospinal fluid levels is achieved after six hours.

PMID- 9190004
TI  - Contribution of calcaneal ultrasonic assessment to the evaluation of
      postmenopausal and glucocorticoid-induced osteoporosis.
AB  - We evaluated ultrasound propagation through the calcaneus using the Achilles
      Lunar unit in patients with postmenopausal or glucocorticoid-induced
      osteoporosis. Speed of sound, broadband ultrasound attenuation and a combination
      of these two parameters called stiffness were determined. Reproducibility was
      0.23%, 2.6%, and 2.6% for these three parameters, respectively. Bone mineral
      density measured at the spine and femoral neck by absorptiometry was
      significantly correlated with all three ultrasound parameters in the women with
      postmenopausal osteoporosis (n = 47) and in the controls (n = 42). In the
      patients with glucocorticoid-induced osteoporosis (n = 35), only speed of sound
      was significantly correlated with the bone mineral density measurements. Mean
      values in the subjects with postmenopausal osteoporosis and in their age-matched
      controls were 1473 +/- 27.2 m/sec versus 1500.6 +/- 29.6 m/sec for speed of
      sound, 95.3 +/- 9.6 dB/Mhz versus 105.7 +/- 10.1 dB/Mhz for broadband ultrasound
      attenuation, and 56.1 +/- 13.2 versus 70.9 +/- 14.1 for stiffness, indicating a
      significant difference (P < 0.01). Z scores were -0.91, -1.1, -0.93, -0.97, and 
      1.05 for bone mineral density at the spine, bone mineral density at the femoral
      neck, speed of sound, broadband ultrasound attenuation and stiffness,
      respectively. Receiver Operating Characteristic curves showed that there were no
      statistically significant differences between the ultrasound parameters at the
      calcaneus and the absorptiometry measurements at the spine and femoral neck. Mean
      values in glucocorticoid-treated patients and age-matched controls were 1480 +/-
      26.9 m/sec versus 1505.1 +/- 30.3 m/sec for speed of sound, 99.2/-11.4 dB/Mhz
      versus 105.9 +/- -10.2 dB/Mhz for broadband ultrasound attenuation, and 60.7 +/-
      14 versus 72.1/14.5 for stiffness, again indicating a significant difference (P <
      or = 0.01). Z scores were -0.55, -0.65, -0.8, -0.67, and -0.78 for bone mineral
      density at the spine, bone mineral density at the femoral neck, speed of sound,
      broadband ultrasound attenuation and stiffness, respectively. Our data suggest
      that ultrasound parameters measured at the calcaneus are useful for evaluating
      postmenopausal and glucocorticoid-induced osteoporosis.

PMID- 9190005
TI  - Lumbar spinal stenosis: a review.
AB  - Neurologic compromise due to degenerative disorders of the lumbar spine are
      designated by the generic term "lumbar spinal stenosis". Differences in the
      interpretation of this term exist across the fields of pathology, radiology, and
      rheumatology, creating significant confusion. Rheumatologists view lumbar spinal
      stenosis as a functional rather than an anatomic entity and hold that its
      diagnosis should be based on clinical grounds. As in disk disease, imaging
      studies lack sensitivity and specificity, are poorly correlated with the level
      and severity of manifestations and are of no assistance for predicting the
      preoperative or postoperative outcome. A detailed history is the mainstay of the
      diagnosis and also carries great weight for estimating the level of impairment
      due to spinal stenosis. In contrast, "objective" physical findings have little
      predictive value and are poorly correlated with both quality of life indicators
      and postoperative outcomes. The effect of surgery remains unpredictable in the
      individual patient. Remarkable uniformity has occurred among published series
      regarding the rate of poor surgical outcomes (about one case in three),
      postsurgical worsening of symptoms (one case in six) and postsurgical
      complications (one case in ten). Accurate data are lacking on the short-term and
      long-term efficacy of conservative therapy (local corticosteroid injections and
      kinesiology). Randomized studies are needed to compare conservative therapy and
      surgery in terms of quality of life and other long-term outcomes in patients who
      fail initially to respond to conservative management. Improved knowledge of the
      natural history of this ill-defined syndrome is among the benefits expected from
      such studies.

PMID- 9190007
TI  - Thromboangiitis obliterans with inaugural rheumatic manifestations. A report of
      three cases.
AB  - Thromboangiitis obliterans, or Buerger's disease, is a segmental occlusive
      inflammatory disorder of the small- and medium-sized arteries and veins seen in
      young adults and associated with cigarette smoking. The lesions are most marked
      in the distal limbs. We report three cases in which the first manifestations were
      rheumatic, consisting in polyarthritis in two cases and carpal tunnel syndrome in
      one. Rheumatic manifestations are infrequent and rarely inaugural in
      thromboangiitis obliterans, although they are probably underdiagnosed. Their
      pathogenesis is unclear but may involve autoimmunity. Heightened awareness of the
      possibility that rheumatic manifestations can inaugurate thromboangiitis
      obliterans may allow an earlier diagnosis of this disease, which may improve the
      functional prognosis. However, recovery can be achieved only if the patient stops
      smoking.

PMID- 9190006
TI  - Floctafenin versus acetaminophen for pain control in patients with osteoarthritis
      in the lower limbs. Franco-Belgian Task Force.
AB  - A multicenter, double-blind, cross-over, random-order study compared the efficacy
      of floctafenin, 800 mg/day and acetaminophen, 3000 mg/day, in providing pain
      relief to 192 patients with chronic pain due to osteoarthritis in the lower
      limbs. Each drug was given for 12 days and the interval between the two treatment
      periods was two days. The primary evaluation criterion was pain relief as
      assessed using the visual analog scale developed by Huskisson (mean baseline
      score, 62.7 +/- 13.6 mm). Secondary criteria were the algofunctional index, the
      investigator's overall efficacy rating and patient preference. Floctafenin
      therapy was associated with significantly better results regarding the visual
      analog scale score (P = 0.036, 149 patients in the per protocol analysis) and the
      investigator's overall efficacy rating (P = 0.0001, 169 evaluable patients).
      Among the 169 evaluable patients, 68 had no preference for either treatment and
      101 had a preference, which was for floctafenin therapy in 65% of cases (P =
      0.001). Clinical tolerance was satisfactory with both drugs. Gastrointestinal
      symptoms were the most common side effects (13% and 11% of patients with
      floctafenin and acetaminophen, respectively).

PMID- 9190008
TI  - Destructive polyarthritis due to a group B streptococcus.
AB  - A new case of destructive polyarthritis due to a Group B streptococcus is
      reported. The patient was a 55-year-old male whose predominantly axial
      manifestations in the absence of evidence of an infection initially suggested
      psoriatic arthritis. Although rare, Group B streptococcal arthritis has been
      reported outside the postpartal and neonatal periods. Monoarthritis with a
      favorable outcome has been the most common clinical pattern. Several cases of
      destructive polyarthritis with axial involvement have been reported in which the
      joint destruction and longer time to diagnosis as compared with monoarticular
      forms resulted in permanent functional impairment.

PMID- 9190009
TI  - Polyarthritis with perinuclear antineutrophil cytoplasmic antibody inaugurating
      microscopic polyangiitis. Report of a case.
AB  - Microscopic polyangiitis, a condition recently differentiated from macroscopic
      periarteritis nodosa, is characterized by small vessel damage, pauciimmune
      necrotizing glomerulonephritis and presence of perinuclear anti-neutrophil
      cytoplasmic antibody (p-ANCA). Arthralgia is a common symptom often present early
      in the disease, and other joint manifestations have also been reported. We report
      a case with polyarthritis as the first manifestation. Perinuclear ANCA was found
      in a moderate titer. A renal biopsy done six months after the onset of joint
      symptoms to investigate rapidly progressive renal failure established the
      diagnosis. The p-ANCA exhibited antimyeloperoxidase specificity. In the
      discussion we review the diagnosis of microscopic polyangiitis and of concomitant
      polyarthritis and p-ANCA production. ANCA is present in some patients with
      rheumatoid arthritis or systemic lupus erythematosus. It is important to
      determine the specificity of the ANCA since presence of p-ANCA with
      antimyeloperoxidase specificity in a patient with polyarthritis is highly
      suggestive of systemic vasculitis.

PMID- 9190010
TI  - Chemodectoma of the cauda equina.
AB  - We report a new case of chemodectoma of the cauda equina, in a 52-year-old male
      who presented with low back pain and sciatica, then rapidly developed cauda
      equina syndrome. Magnetic resonance imaging demonstrated a tumor at the L2-L3
      level. Complete excision was performed and the tumor was found to be a
      chemodectoma. Chemodectomas are rare neural crest tumors that are usually located
      at the neck. About 70 cases involving the cauda equina have been reported. Most
      are benign, although local recurrences occur in 4% of cases. A case with a
      cerebellar metastasis has been reported. Long-term follow-up should be provided.

PMID- 9190011
TI  - Spinal tuberculosis in an unusual location.

PMID- 9190012
TI  - Paraneoplastic palmar fasciitis and achalasia-like esophageal disorder in a
      patient with breast cancer.

PMID- 9190013
TI  - Adult onset Still's disease and Kikuchi's disease. A new case.

PMID- 9190014
TI  - Thromboangiitis obliterans with arthralgia, diarrhea and nodules as the first
      symptoms.

PMID- 9190015
TI  - Animal mycoplasmoses: a general introduction.
AB  - The nature of the smallest prokaryotes with autonomous replication, i.e. the
      mycoplasmas, which constitute the class Mollicutes, is presented in brief. These
      micro-organisms are extracellular parasites of the mucous membranes in animals.
      Mycoplasmas may cause infections, known as mycoplasmoses. The author describes
      current knowledge of the pathogenicity of mycoplasmas, especially in regard to
      the diverse effects on the immune system and the variability of the superficial
      antigens. Relatively few species of pathogenic mycoplasmas cause mycoplasmoses
      (both sporadic and endemic diseases) which have significant socio-economic
      consequences. The control and prevention of endemic mycoplasmoses can only be
      achieved with effective diagnostic tools and an efficient structure of
      epidemiological surveillance. The author recommends the encouragement of
      biological and genetic research on the mycoplasmas and the co-ordination of the
      development of diagnostic tests, including evaluation and validation in various
      epidemiological field situations.

PMID- 9190016
TI  - Early methods of surveillance and control for contagious bovine pleuropneumonia.
AB  - From the many existing documents on the history of contagious bovine
      pleuropneumonia, it is possible to describe the practical measures adopted for
      disease surveillance and control from ancient times until the 19th century.
      Surveillance was based on diagnosis, post-mortem examination, animal inoculation
      and also on knowledge of the conditions under which infection occurred:
      aetiology, pathogenesis, mode of infection, susceptible species, virulent
      material, incubation period, etc. The historical facts are assembled and
      compared, with comments on each of these points. Control was based upon the
      application of health control measures or vaccination. A study of these two
      procedures makes it possible to compare their efficacy and to describe the
      principal steps in their implementation.

PMID- 9190017
TI  - Manifestation and epidemiology of contagious bovine pleuropneumonia in Africa.
AB  - Contagious bovine pleuropneumonia (CBPP) is one of the major threats to cattle
      health and production in Africa. This article reviews the clinical
      manifestations, lesions and epidemiology of the disease. The clinical
      manifestations and lesions are typical and are no different in Africa from those
      seen in other countries. CBPP is a respiratory disease characterised by pneumonia
      and serofibrinous pleurisy. The usual form of this disease is acute but chronic
      forms are frequent, particularly in endemic regions. Hyperacute forms, with a
      high mortality rate, can be seen at the beginning of outbreaks in newly infected
      regions. The epidemiology of the disease in Africa is dominated by four factors,
      namely: cattle are the only species affected, there is no reservoir in wild
      animals, clinical cases or chronic carriers are the usual sources of infection,
      through direct contact, and cattle movements play a very important role in the
      maintenance and extension of the disease. CBPP is widespread in Africa and,
      according to the Office International des Epizooties and to various reports in
      1995, the disease is present in 24 countries of tropical Africa. In western
      Africa, CBPP is mainly enzootic or sporadic but in some countries the incidence
      is increasing. The situation in Central Africa is not very alarming. However, in
      eastern and south-eastern Africa, CBPP has become a major issue, placing southern
      Africa under direct threat. An evaluation of economic losses due to the disease
      and the cost-benefit ratio of control programmes is indispensable, since such
      economic assessments are needed before policy-makers decide on programmes of
      control or eradication. This is an area which needs to be addressed immediately,
      as the launching of new campaigns, particularly in eastern and southern Africa,
      is urgently needed.

PMID- 9190018
TI  - Manifestation and epidemiology of contagious bovine pleuropneumonia in Europe.
AB  - The authors describe the clinical profile and epidemiology of contagious bovine
      pleuropneumonia in Europe. This disease, once considered to have been eradicated
      several years ago, has now become endemic in southern countries of Europe. The
      status of contagious bovine pleuropneumonia in Portugal and Italy, and the
      evolution of the disease during the last ten years, are analysed in detail, in
      addition to the measures undertaken for control and eradication. The authors also
      refer to hosts and possible reservoirs of the infection.

PMID- 9190019
TI  - Contagious bovine pleuropneumonia vaccines: the current situation and the need
      for improvement.
AB  - The control of contagious bovine pleuropneumonia (CBPP) has been clearly
      identified by the Organisation of African Unity/Inter-African Bureau of Animal
      Resources as a priority. In the first part of this article, the authors introduce
      the past and present vaccines, based on the two classic strains, T1, and KH3J.
      They describe the guidelines for vaccine production technology, and the quality
      control requirements for CBPP vaccines of the Office International des
      Epizooties. The failure of the currently used T1-SR vaccine to provoke
      satisfactory immunity in cattle, particularly in the newly infected areas of
      Africa, is pointed out. Other shortcomings of the current CBPP vaccines are also
      highlighted. Thus, there is a need to improve CBPP vaccines and the authors
      propose detailed emergency measures to address this problem. In the second part
      of the article, a subunit approach using immunostimulating complex technology is
      outlined. The authors emphasise the importance of current research in cell
      mediated immunity and immunopathology, which is aimed at improving the efficacy
      of CBPP vaccines.

PMID- 9190020
TI  - Contagious caprine pleuropneumonia and other pulmonary mycoplasmoses of sheep and
      goats.
AB  - Contagious caprine pleuropneumonia (CCPP) is now a well-defined disease that is
      caused by Mycoplasma capricolum subsp. capripneumoniae. CCPP is infectious,
      contagious and fulfils the classic Koch postulates that characterise such types
      of disease. The distribution of the disease is not exactly known, but reports of
      mycoplasma isolation and official declarations to the Office International des
      Epizooties (OIE) enable a probable distribution map to be obtained. There are
      many other mycoplasmas that can infect goat and sheep lungs and induce
      pleuropneumonia. However, pleuropneumonia is often restricted to young animals
      and the prominent symptom is mastitis in lactating does. Other symptoms may also
      occur, contributing to a syndrome that has been tentatively described in this
      paper as 'MAKePS syndrome' for mastitis, arthritis, keratitis, pneumonia and
      septicaemia.

PMID- 9190021
TI  - Diagnosis and control of contagious caprine pleuropneumonia.
AB  - The diagnosis of contagious caprine pleuropneumonia (CCPP) has often been
      considered difficult. This is because of the confusion that can arise with other
      mycoplasmoses of small ruminants. Symptoms and lesions can be similar and the
      isolation of M. capricolum subsp. capripneumoniae (MccF38) requires skilled
      technicians. Once MccF38 strains are isolated, their identification should not be
      difficult. New techniques, such as polymerase chain reaction, now offer the
      possibility of identifying MccF38 directly from dried samples. However, the
      isolation of MccF38 strains is always required for an official declaration of
      infection. Until now, the official serological test has been the complement
      fixation test; the main drawbacks being lack of sensitivity and specificity and
      also the short persistence of antibodies detected by this technique. The specific
      competition enzyme-linked immunosorbent assay has now been developed and should
      enable wide serological enquiries to determine the real prevalence of the
      disease. Antibiotic treatments are effective but may not prevent persistence in
      latent carriers. An inactivated vaccine with saponin as an adjuvant has been
      produced in Kenya, which protects goats for approximately one year.

PMID- 9190023
TI  - Mycoplasmoses in poultry.
AB  - The most important mycoplasmas isolated from domestic avian species include
      Mycoplasma gallisepticum (MG), M. synoviae (MS), M. meleagridis (MM) and M. iowae
      (MI). MG causes chronic respiratory disease of chickens and infectious sinusitis
      in turkeys, resulting in economic losses. MS causes infectious synovitis or mild
      upper respiratory disease. MM infects only turkeys, causing airsacculitis and sub
      optimal production and hatchability. MI is associated with reduced hatchability
      in turkey flocks. Transmission is either direct, from bird to bird or through the
      egg, or indirect. Diagnosis is based on isolation and identification of
      mycoplasmas, according to biochemical, serological or molecular biology tests, or
      serological examination of host sera by slide agglutination, haemagglutination
      inhibition or enzyme-linked immunosorbent assay (ELISA) tests. Antibiotics (i.e.
      tetracyclines, macrolides, quinolones and tiamulin) may be used for therapeutic
      treatment or prophylactic medication. The eradication of mycoplasma infection can
      be achieved through improvements in hygiene and management practices, therapeutic
      treatment of breeder layers and/or of hatching eggs and better monitoring
      procedures.

PMID- 9190022
TI  - Mycoplasma bovis as an agent of mastitis, pneumonia, arthritis and genital
      disorders in cattle.
AB  - Bovine diseases due to Mycoplasma bovis can cause considerable economic losses in
      cattle production. While the pathogen is principally responsible for therapy
      resistant mastitis on large dairy farms, on smaller farms the typical mycoplasma
      diseases are calf pneumonia and arthritis. Moreover, the pathogen is able to
      cause genital disorders. M. bovis infection can be controlled effectively only if
      appropriate measures are implemented at the earliest possible stage. Since
      immunoprophylaxis and antibiotic treatment are known to be ineffective, control
      measures must include the introduction of strict hygiene standards, the
      restriction of animal movement out of infected herds and the culling of
      clinically diseased animals and shedders of the mycoplasma (the latter only in
      the case of mastitis and genital disorders). In this review, symptoms of the
      various diseases caused by M. bovis are described and characteristics of the
      course of infection are outlined. To clarify the origin and spread of the
      infection, the authors describe the main properties and reservoirs of the
      pathogen and summarise experimental evidence on modes of transmission to
      susceptible organs. As effective diagnosis is a prerequisite for the introduction
      of early control measures, the advantages and disadvantages of currently used
      diagnostic methods are discussed in detail. It is a serious shortcoming if
      testing for mycoplasmas is not included in routine bacterial examination of
      clinical samples. As a consequence, some M. bovis infections will remain
      undetected and outbreaks cannot be controlled properly. Finally, practical
      recommendations are given for prevention and control, including the formation of
      mycoplasma-free herds.

PMID- 9190024
TI  - Control of avian mycoplasmoses by vaccination.
AB  - Vaccination is an option for controlling Mycoplasma gallisepticum or M. synoviae
      when biosecurity measures fail to prevent the infection of poultry flocks with
      these mycoplasmas. Both killed vaccines (bacterins) and living vaccines are
      currently in commercial use. Bacterins usually contain an oil emulsion adjuvant
      and are administered by subcutaneous or intramuscular injection. They can reduce
      the decline in egg production associated with M. gallisepticum, although they do
      not prevent infection. Newer adjuvants, such as immune stimulating complexes, may
      provide effective immunity without the tissue lesions caused by oil emulsion
      adjuvants. Living M. gallisepticum vaccines include the F strain and attenuated
      strains ts-11 and 6/85. F strain is administered in drinking water or by aerosol.
      This strain reduces the decline in egg production and has been used to displace
      endemic strains in multiple-age flocks. The major disadvantage is the inherent
      virulence of F strain. Strain ts-11 is less virulent and less infectious than F
      strain and provides a somewhat weaker, but usually effective, long-term
      protective immunity, which is vaccine-dose dependent. This strain is administered
      by eye drop, persists in the chicken for long periods and stimulates a detectable
      although variable systemic antibody response. Strain ts-11 can be used safely in
      combination with respiratory virus vaccines. Strain 6/85 also stimulates a weaker
      protective immune response than F strain and is of low virulence and infectivity.
      This strain is administered by aerosol, appears not to persist in vaccinated
      birds and may fail to stimulate a detectable systemic antibody response. Strain
      MS-H is currently being evaluated as a live vaccine against M. synoviae in meat
      chicken breeder flocks and is often used in conjunction with strain ts-11.

PMID- 9190025
TI  - Avian mycoplasmosis in Asia.
AB  - Since 1954, avian mycoplasmosis has been considered a significant problem in
      chicken flocks in Japan and in other Asian countries. In Japan, Mycoplasma
      gallisepticum (MG) and M. synoviae (MS) infections were confirmed aetiologically
      in chicken flocks affected with respiratory disease or synovitis in 1962 and
      1973, respectively. In other Asian countries, including Indonesia, the People's
      Republic of China, Korea, Malaysia, the Philippines, Taipei China and Thailand,
      the occurrence of mycoplasmosis in chicken flocks has been recognised
      serologically or aetiologically. Adverse atmospheric and environmental
      conditions, in addition to mixed infections of bacterial or viral origin, play an
      important role in the spread of MG and MS within chicken flocks or in the
      induction of clinical respiratory mycoplasmosis. Serological tests are important
      in determining and monitoring the mycoplasmal infection status of chicken flocks.
      The establishment of mycoplasma-free breeding stocks is recognised as essential
      for the control of avian mycoplasmosis. To eliminate the transmission of MG to
      the egg, treatment of infected breeder flocks or their progeny with anti
      mycoplasmal antibiotics was effective in considerably reducing the infection rate
      but not in entirely eliminating MG infection. The preincubation heat treatment of
      chicken hatching eggs has proved an effective procedure for establishing MG- and
      MS-free breeding stocks in Japan. Vaccination against MG infection has been
      practised successfully in Japan and other countries.

PMID- 9190026
TI  - Swine mycoplasmoses.
AB  - Mycoplasma hyopneumoniae is the primary agent of enzootic pneumonia in pigs. The
      lung lesions, generally observed in young pigs, are characterised by a
      hyperplasia of the epithelial cells and an increased perivascular and
      peribronchiolar accumulation of mononuclear cells. Following M. hyopneumoniae
      infection, immune reactions are observed and resistance is induced in pigs.
      Laboratory diagnosis is generally performed by an immunofluorescent test and by
      enzyme-linked immunosorbent assay. Antibiotics are useful but the development of
      resistance has been described. Vaccination seems to be an effective method of
      controlling the disease. M. hyorhinis, generally transmitted by sows to piglets
      through nasal secretions, exists in a high percentage in the respiratory tract of
      healthy pigs. But some strains can induce serofibrinous to fibrinopurulent
      polyserositis and arthritis. M. hyorhinis is isolated from acute and subacute
      phase lesions and serum antibodies are detectable. M. hyosynoviae has a special
      affinity for joint tissue and may cause arthritic disease, leading to economic
      losses. This mycoplasma is generally located in the tonsils. Piglets are infected
      by sows after four to six weeks of life. Evidence of disease occurs in animals of
      between 30 to 40 kg and 100 kg, and bursae and joints are affected. A non
      suppurative viscous fluid of a serofibrinous/serosanguineous nature is reported.
      In chronic cases, the synovial membrane is affected. M. hyosynoviae is isolated
      from the joints and pharyngeal/tonsillar samples and can induce antibodies in
      blood and joint fluid. Predisposing factors play an important role. M. flocculare
      is widely distributed in swine, in normal and pneumonic lungs and in nasal
      cavities, but no pathogenic capability has been described. There is great
      interest in this mycoplasma because of the great similarity to M. hyopneumoniae.

PMID- 9190027
TI  - Evidence-based medicine.
AB  - Evidence-based medicine, whose philosophical origins extend back to mid-19th
      century Paris and earlier, is the conscientious, explicit and judicious use of
      current best evidence in making decisions about the care of individual patients.
      The practice of evidence-based medicine means integrating individual clinical
      expertise with the best available external clinical evidence from systematic
      research. By individual clinical expertise we mean the proficiency and judgment
      that we individual clinicians acquire through clinical experience and clinical
      practice. Increased expertise is reflected in many ways, but especially in more
      effective and efficient diagnosis and in the more thoughtful identification and
      compassionate use of individual patients' predicaments, rights, and preferences
      in making clinical decisions about their care. By best available external
      clinical evidence we mean clinically relevant research, often from the basic
      sciences of medicine, but especially from patient centered clinical research into
      the accuracy and precision of diagnostic tests (including the clinical
      examination), the power of prognostic markers, and the efficacy and safety of
      therapeutic, rehabilitative, and preventive regimens. External clinical evidence
      both invalidates previously accepted diagnostic tests and treatment and replaces
      them with new ones that are more powerful, more accurate, more efficacious, and
      safer. Good doctors use both individual clinical expertise and the best available
      external evidence, and neither alone is enough. Without clinical expertise,
      practice risks becoming tyrannized by external evidence, for even excellent
      external evidence may be inapplicable to or inappropriate for an individual
      patient. Without current best external evidence, practice risks becoming rapidly
      out of date, to the detriment of patients. The practice of evidence-based
      medicine is a process of life-long, self-directed learning in which caring for
      our own patients creates the need for clinically important information about
      diagnosis, prognosis, therapy, and other clinical and health care issues, and in
      which we (1) convert these information needs into answerable questions; (2) track
      down, with maximum efficiency, the best evidence with which to answer them
      (whether from the clinical examination, the diagnostic laboratory from research
      evidence, or other sources); (3) critically appraise that evidence for its
      validity (closeness to the truth) and usefulness (clinical applicability); (4)
      integrate this appraisal with our clinical expertise and apply it in practice;
      and (5) evaluate our performance.

PMID- 9190028
TI  - Fetal medicine.
AB  - Fetal medicine is the practice of medicine where the patient is the fetus. The
      traditional activities of clinical medicine: prevention, screening, diagnosis,
      and therapy are directed at decreasing, identifying and treating fetal disease.
      Examples of successful preventative, screening, diagnostic and therapeutic
      maneuvers involving the fetus are presented. A plea is made for the systematic
      evaluation of the new technology being developed in fetal medicine. The same
      standard of evidence-the randomized, controlled clinical trial-which is more and
      more applied to traditional medical practice-should also be the gold standard for
      fetal medicine.

PMID- 9190029
TI  - Red blood cell transfusions for preterm infants: the role of evidence-based
      medicine.
AB  - Increasingly clinicians attempt to base decisions regarding patient management on
      the results of clinical studies in addition to expert opinion and their own
      practical experience. In this article, the author reviews the published studies
      available to assist clinicians to make evidence-based decisions in three topics
      related to small volume red blood cell (RBC) transfusions for preterm infants;
      namely, studies examining the effects of RBC transfusions on possible symptoms of
      anemia such as tachypnea, apnea or other cardiorespiratory irregularities,
      studies investigating the collection and transfusion of umbilical cord blood and
      finally studies addressing the duration of storage and use of additive solutions
      for RBCs for transfusion to neonates. Based on the review of these studies,
      guidelines for small volume RBC transfusions in preterm infants are suggested.

PMID- 9190030
TI  - The role of erythropoietin in the anemia of prematurity.
AB  - Neonatal erythropoiesis is limited by a relatively inadequate production of
      erythropoietin. This is likely the result of dependence on the hepatic production
      of erythropoietin and an incomplete switchover to renal production. The present
      model of neonatal erythropoiesis suggests that the use of exogenous
      erythropoietin should correct the early anemia of prematurity that is observed at
      6 weeks of age in premature newborns. Randomized, controlled trials of
      erythropoietin use in very low birthweight infants are reviewed. The data support
      the conclusion that erythropoietin at doses of > or = 750 u/kg/wk started at less
      than 7 days of age results in improved reticulocyte counts and hemoglobin levels,
      but does not reduce the number of infants who will be exposed to blood products.
      Erythropoietin at doses of > or = 600 u/kg/wk started at an average of 21 days of
      life improves reticulocyte counts and hemoglobin levels, and reduces the number
      of infants will will require late transfusion, but does nothing for the bulk of
      infants who are transfused before that age.

PMID- 9190031
TI  - Neonatal sepsis: pathogenesis and supportive therapy.
AB  - Bacterial infections remain an important cause of neonatal mortality and
      morbidity. Pathogenesis of the neonate's predilection to infection are
      multifactorial. Factors directly attributable to the infant include humoral,
      phagocytic, and cellular deficiencies. Septic neonates may have reduced
      neutrophil storage pools that cause profound neutropenia. Both correlate with
      poor prognosis. Antibiotic administration is mandatory in neonatal sepsis.
      Supplementary treatments may be useful. Granulocyte transfusions, when available,
      provide neutrophils, improving the neonate's neutrophil count and neutrophil
      function. The efficacy of intravenous immunoglobulin (i.v.IG) is questionable
      because the prophylactic and therapeutic administration of i.v.IG fails to reduce
      the incidence of bacterial infections or affect the overall survival rate.
      Hyperimmune preparations seem to be more effective. The administration of
      granulocyte colony-stimulating factor induces myeloid progenitor proliferation,
      enhances the neutrophil storage pool, produces neutrophilia, and improves
      neutrophil function. More extensive, well-designed, and carefully control trials
      are needed to determine the benefit of supportive therapies for neonatal sepsis.

PMID- 9190032
TI  - The management of hemolytic disease in the fetus and newborn.
AB  - Rh hemolytic disease (HDN) is the prototype of maternal alloimmunization and
      fetal hemolytic disease. There are other antigens capable of causing
      alloimmunization and hemolytic disease such as c, Kell, and Fya. Rh immunization
      is usually caused by a prior Rh positive fetal maternal transplacental
      hemorrhage, which occurs in at least 75% of pregnancies. Unless treated,
      hemolytic disease will result in kernicterus or fetal hydrops in 25% of cases,
      respectively. Neonatal exchange transfusion has eradicated kernicterus. Measures
      available to predict severity of fetal hemolytic disease are maternal antibody
      titers, prior history of hemolytic disease, in vitro cell-mediated maternal
      antibody functional assays, amniotic fluid spectrophotometry, ultrasound fetal
      assessment, and fetal blood sampling. The Rh or Kell antigen status of the fetus
      may be determined by amniotic fluid PCR testing. The management of the severely
      affected fetus consists of early delivery, with or without fetal transfusions,
      depending on the gestation of the fetus. With the use of these diagnostic and
      treatment measures, perinatal mortality from hemolytic disease of the fetus and
      newborn has been reduced in Manitoba, population one million, from 100 per year
      in the early 1940s to 1 every 3 years in the mid 1990s.

PMID- 9190033
TI  - Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) is an uncommon (1 in 2,000
      livebirths) but serious disorder characterized by marked thrombocytopenia in the
      fetus and neonate. Platelet destruction is caused by a maternal antibody directed
      against a fetal platelet antigen inherited from the father and lacking in the
      mother's platelets. Intracranial hemorrhage (ICH) is the most devastating
      complication of NAIT, affecting approximately 20% of all proven cases, up to 50%
      of which occur antenatally. Because close to 100% of subsequent pregnancies will
      be equally or more severely affected, antenatal management directed at preventing
      ICH in utero has assumed great clinical importance. In recent years, considerable
      progress has been made in this regard, and although clinical uncertainties still
      exist, the natural history of this disease and its response to various antenatal
      interventions have become reasonably well understood. This review will focus on
      the diagnosis and current management of NAIT, including controversies surrounding
      current treatment modalities and future prospects for treatment and prevention.

PMID- 9190034
TI  - Platelet disorders in newborn infants: diagnosis and management.
AB  - Platelets are small, disc-shaped, anucleated cells formed by fragmentation of
      megakaryocytes in the bone marrow. They circulate in blood with a lifespan of 7
      to 10 days and, together with fibrin, form hemostatic plugs at sites of vessel
      injury. Abnormalities of platelets, either quantitative or qualitative, may cause
      clinically significant bleeding with resultant morbidity and, on occasion,
      mortality. This review will focus on platelet disorders in neonates, defined as
      infants of up to 4 months of age. Special emphasis will be given to the
      physiology of platelet function in healthy and sick newborn infants. The review
      will be divided into sections as follows: role of platelets in hemostasis,
      platelet function in newborn infants, quantitative platelet disorders,
      qualitative platelet disorders, and platelet transfusion therapy.

PMID- 9190035
TI  - Fetal erythropoiesis and the diagnosis and treatment of hemoglobin disorders in
      the fetus and child.
AB  - Although synthesis of adult hemoglobin (alpha 2 beta 2) is reduced or absent in
      both alpha and beta thalassemias, these disorders differ in their clinical
      significance to the fetus and neonate. alpha-Globin synthesis is observed in the
      yolk sac by 3 weeks of gestation and, by 9 weeks of gestation, alpha-globin
      represents the main alpha-like hemoglobin in the fetus. By contrast, the switch
      to beta-globin chain synthesis usually remains incomplete until 1 year after
      birth. Therefore, the clinical manifestations of homozygous beta-thalassemia may
      be ameliorated by sustained synthesis of fetal hemoglobin during the first 6
      months of life, whereas up until 10 years ago, homozygous alpha-thalassemia was
      invariably associated with death in utero. More recently, reports of infants with
      homozygous alpha-thalassemia surviving the neonatal period have emerged,
      observations particularly relevant to large numbers of immigrants to North
      America from Southeast Asia, where alpha-thalassemia is common. Studies of
      patients with the beta-globin disorders thalassemia and sickle cell disease
      showed that the severity of both disorders is ameliorated by sustained synthesis
      of fetal hemoglobin into adult life. Hence, treatment for both these disorders
      has focused on the pharmacological manipulation of fetal hemoglobin. Studies in
      vitro, in animal models, and in affected patients have shown that several
      compounds stimulate gamma-globin synthesis and fetal hemoglobin production
      through a variety of proposed mechanisms. Some of the successes in human trials
      are outlined herein.

PMID- 9190036
TI  - The relevance of developmental hemostasis to hemorrhagic disorders of newborns.
AB  - The hemostatic system is a dynamic evolving process that is age-dependent.
      Components of the hemostatic system are synthesized in early fetal life and do
      not cross the placenta from mother to fetus. However, plasma concentrations of
      proteins involved in hemostasis significantly differ from adults. Physiological
      reference ranges are available for premature infants, full-term infants and
      children from ages 1 to 16 years. In the coagulation system, plasma
      concentrations of the vitamin K-dependent and contact factors are decreased at
      birth, whereas other factors such as fibrinogen, FV, FVIII, and FXIII are similar
      or increased compared with adults at birth. In the fibrinolytic system, plasma
      concentrations of plasminogen are decreased at birth, whereas tissue plasminogen
      activator and plasminogen activator inhibitor are increased. Clinically, the
      hemostatic system of the young is effective and healthy infants do not suffer
      from spontaneous hemorrhagic complications. However, infants are more vulnerable,
      compared with older patients, for bleeding in the presence of either congenital
      or acquired haemostatic defects. Severe congenital bleeding disorders, although
      rare, frequently present in the newborn period. The most common acquired causes
      of bleeding newborns include disseminated intravascular coagulation, vitamin K
      deficiency, and liver disease. A description of these disorders and treatment
      guidelines are provided.

PMID- 9190037
TI  - The etiology, diagnosis and treatment of thrombotic disorders in newborn infants:
      a call for international and multi-institutional studies.
AB  - OBJECTIVE: To examine the present state of knowledge on the etiology, diagnosis,
      and treatment of neonatal thrombosis. METHODS: A Medline search (exp infant,
      newborn, and exp thrombosis, and prospective studies) was performed to identify
      high-quality articles that have been published during the last 30 years. RESULTS:
      The retrieval rate increased from less than one citation per year to an average
      of three per year in the current Medline file. An intravascular catheter is the
      most common risk factor for the development of neonatal thrombosis (excluding
      strokes). Little is known about the precision and accuracy of noninvasive imaging
      techniques, which are commonly used to make the diagnosis. The efficacy and
      safety of anticoagulant or thrombolytic therapy remain uncertain. CONCLUSIONS:
      The published literature on neonatal thrombotic disorders continues to show a
      shortage of well-designed international and multi-institutional studies. The
      latter are urgently needed to rationalize the management of affected infants.

PMID- 9190038
TI  - The riddle of vitamin K1 deficit in the newborn.
AB  - Vitamin K in the fetus and newborn is maintained at levels less than that
      necessary to achieve full gamma-carboxylation of the K-dependent proteins,
      including those required for hemostasis. As the infant matures and even into
      adulthood, there is no significant storage pool for this vitamin, and a K1
      deficient state can be produced by placing an adult on a K-deficient diet for 7
      to 10 days. Questions arise as to why the level of vitamin K is so rigidly
      controlled and why the placental gradient in humans and other mammals maintains
      the fetus in a K-"deficient" state. The evidence is reviewed that suggests that K
      dependent proteins are ligands for receptor tyrosine kinases, which, in the
      rapidly proliferating cell milieu of the fetus, control growth regulation.
      Increased stimuli may result in growth dysregulation whereas conversely, the
      further depletion of vitamin K-dependent proteins, as in warfarin toxicity,
      depletes the required stimuli for normal embryogenesis. These findings argue for
      the need for tightly controlled levels of vitamin K consistent with normal
      embryogenesis.

PMID- 9190039
TI  - Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome.
AB  - Approximately 10% of newborn infants with Down Syndrome develop a form of
      megakaryoblastic leukemia which usually disappears spontaneously during the first
      months of life. The evidence that this "Transient Leukemia" is truly leukemia
      includes the following: it is clonal proliferation, it can be fatal and tissue
      infiltration of leukemic cells occurs. Also in approximately 25% of cases that
      recover, Acute Megakaryoblastic Leukemia will develop in the first four years of
      life, which, if not treated, is fatal. Evidence regarding the megakaryoblastic
      nature of the leukemic cells is presented as well as a description of the lethal
      forms of the disease. The study of Transient Leukemia is of considerable
      importance because it can provide insight into both the nature of leukemia and
      its relation to trisomy 21.

PMID- 9190040
TI  - Neonatal oncology: diagnostic and therapeutic dilemmas.
AB  - Tumors are a rare but important cause of mortality and morbidity in the neonate.
      There is a wide spectrum of benign and malignant tumors that can occur, some of
      which have a unique presentation and behavior in this age group. It is important
      to recognize that tumors such as stage IVS neuroblastoma, which have a good
      prognosis in older children, may be rapidly fatal in the newborn and constitute
      an oncological emergency. Other tumors behave in a less aggressive fashion at
      this age than in the older child, and should not be overtreated. An increasing
      number of tumors are being detected by prenatal screening, and understanding of
      their natural history and management is important. Management of neonatal cancer
      requires knowledge also of the developmental biology of the neonate, of the way
      in which they handle drugs, and the increased potential for acute toxicity and
      long-term morbidity from chemotherapy and radiation therapy.

PMID- 9190041
TI  - Tyrosyl radicals in enzyme catalysis: some properties and a focus on
      photosynthetic water oxidation.
AB  - Enzymes that require a redox-active amino acid for catalysis or function have
      emerged as a distinct class of proteins. For the tyrosine-based radical enzymes,
      we show that the spin-density distribution in the radical follows an odd
      alternate pattern that is invariant to within 10% across the class. General
      properties of the radical enzymes are summarized from which we conclude that
      their essential role in catalysis is to initiate substrate metabolism by hydrogen
      atom abstraction. These ideas are extended to the YZ and YD tyrosines in
      Photosystem II and a radical-based hydrogen-atom abstraction model for water
      oxidation is discussed. Differences in rates of oxidation of YZ and YD by the
      reaction-center chlorophyll, P680+, under various conditions, are considered and
      rationalized on the basis of changes in reorganization energy induced by the
      local protein structure and by the presence or absence of the (Mn)4 cluster that
      binds substrate water.

PMID- 9190042
TI  - Interaction of MRI gadolinium contrast agents with phospholipid bilayers as
      studied by 95 GHz EPR.
AB  - Interactions of two MRI gadolinium contrast agents, gadolinium ethoxybenzyl
      diethylenetriaminepentaacetate (Gd-EOB-DTPA) and gadolinium N-pentyl-1,4,7,10
      tetraazacyclododecane-N',N",N'"- triacetic acid (Gd-DOTA-P), with multibilayer
      phospholipid dispersions prepared from 1,2-dipalmitoyl-sn-glycero-3
      phosphatidylcholine (DPPC) have been investigated with high resolution EPR
      spectroscopy at 95 GHz. At a resonance field of 3.3 T, EPR spectra of a small
      nitroxide probe, 2,2,6,6-tetramethyl-1-piperidinyloxyl (Tempo), partitioned
      between aqueous and membrane phases are clearly resolved, making measurements of
      dynamics parameters of the probe accurate and unambiguous. Results show that
      although the presence of the more lipophilic contrast agent, Gd-DOTA-P, can be
      detected within the bilayer, the structural organization of the membrane remains
      unaffected even at physiologically high (5 mM) concentrations. The temperature of
      the main phase transition of the bilayer was also unaffected to within the 0.4
      degree C accuracy of its determination.

PMID- 9190043
TI  - Segmentally distributed metamorphic changes in neural circuits controlling
      abdominal bending in the hawk moth Manduca sexta.
AB  - During the metamorphosis of Manduca sexta the larval nervous system is
      reorganized to allow the generation of behaviors that are specific to the pupal
      and adult stages. In some instances, metamorphic changes in neurons that persist
      from the larval stage are segment-specific and lead to expression of segment
      specific behavior in later stages. At the larval-pupal transition, the larval
      abdominal bending behavior, which is distributed throughout the abdomen, changes
      to the pupal gin trap behavior which is restricted to three abdominal segments.
      This study suggests that the neural circuit that underlies larval bending
      undergoes segment specific modifications to produce the segmentally restricted
      gin trap behavior. We show, however, that non-gin trap segments go through a
      developmental change similar to that seen in gin trap segments. Pupal-specific
      motor patterns are produced by stimulation of sensory neurons in abdominal
      segments that do not have gin traps and cannot produce the gin trap behavior. In
      particular, sensory stimulation in non-gin trap pupal segments evokes a motor
      response that is faster than the larval response and that displays the triphasic
      contralateral-ipsilateral-contralateral activity pattern that is typical of the
      pupal gin trap behavior. Despite the alteration of reflex activity in all
      segments, developmental changes in sensory neuron morphology are restricted to
      those segments that form gin traps. In non-gin trap segments, persistent sensory
      neurons do not expand their terminal arbors, as do sensory neurons in gin trap
      segments, yet are capable of eliciting gin trap-like motor responses.

PMID- 9190044
TI  - Multisegmental motor activity in the segmentally restricted gin trap behavior in
      Manduca sexta pupae.
AB  - Stimulation of sensory neurons innervating hairs in the gin traps on the abdomen
      of Manduca sexta pupae evokes a rapid bending of the abdomen that is restricted
      to one or more of the three articulating posterior segments. However, electrical
      stimulation of the gin trap sensory nerve in an isolated abdominal nerve cord
      evokes characteristic motor neuron activity in every abdominal segment. To
      determine if the segmentally distributed motor activity also occurred in intact
      animals and how it contributed to the segmentally restricted reflex movement,
      mechanical stimulation of the sensory hairs in intact animals was used to evoke
      reflex responses that were recorded as electromyograms synchronized with video
      recordings of the behavior. Motor activity was monitored during movements to
      determine if there was activity in many segments when the movement was restricted
      to one segment. Coordinated muscle activity was evoked throughout the abdomen in
      response to stimulation of any of the three gin traps, even when movement was
      restricted to one segment. Differences in the timing of ipsilateral and
      contralateral motor activity among segments allowed the closing of gin traps to
      be segmentally restricted. These findings suggest that the neural circuit
      underlying the gin trap reflex is distributed throughout the abdominal nerve
      cord. This network generates a complex, yet coordinated, motor pattern with
      muscular activity in many abdominal segments that produces a localized bending
      reflex.

PMID- 9190045
TI  - Short latency vestibular evoked potentials in the Japanese quail (Coturnix
      coturnix japonica).
AB  - Short-latency vestibular-evoked potentials to pulsed linear acceleration were
      characterized in the quail. Responses occurred within 8 ms following the onset of
      stimuli and were composed of a series of positive and negative peaks. The
      latencies and amplitudes of the first four peaks were quantitatively
      characterized. Mean latencies at 1.0 g ms-1 ranged from 1265 +/- 208 microseconds
      (P1, N = 18) to 4802 +/- 441 microseconds (N4, N = 13). Amplitudes ranged from
      3.72 +/- 1.51 microV (P1/N1, N = 18) to 1.49 +/- 0.77 microV (P3/N3, N = 16).
      Latency-intensity (LI) slopes ranged from -38.7 +/- 7.3 microseconds dB-1 (P1, N
      = 18) to -71.6 +/- 21.9 microseconds dB-1 (N3, N = 15) and amplitude-intensity
      (AI) slopes ranged from 0.20 +/- 0.08 microV dB-1 (P1/N1, N = 18) to 0.07 +/-
      0.04 microV dB-1 (P3/N3, N = 11). The mean response threshold across all animals
      was -21.83 +/- 3.34 dB re: 1.0 g ms-1 (N = 18). Responses remained after cochlear
      extirpation showing that they could not depend critically on cochlear activity.
      Responses were eliminated by destruction of the vestibular end organs, thus
      showing that responses depended critically and specifically on the vestibular
      system. The results demonstrate that the responses are vestibular and the
      findings provide a scientific basis for using vestibular responses to evaluate
      vestibular function through ontogeny and senescence in the quail.

PMID- 9190047
TI  - The pattern of sensory discharge can determine the motor response in young
      Xenopus tadpoles.
AB  - Young Xenopus tadpoles were used to test whether the pattern of discharge in
      specific sensory neurons can determine the motor response of a whole animal.
      Young Xenopus tadpoles show two main rhythmic behaviours: swimming and
      struggling. Touch-sensitive skin sensory neurons in the spinal cord of
      immobilised tadpoles were penetrated singly or in pairs using microelectrodes to
      allow precise control of their firing patterns. A single impulse in one Rohon
      Beard neuron (= light touch) could sometimes trigger "fictive" swimming. Two to
      six impulses at 30-50 Hz (= a light stroke) reliably triggered fictive swimming.
      Neither stimulus evoked fictive struggling. Twenty-five or more impulses at 30-50
      Hz (= pressure) could evoke a pattern of rhythmic bursts, distinct from swimming
      and suitable to drive slower, stronger movements. This pattern showed some or all
      the characteristics of "fictive" struggling. These results demonstrate clearly
      that sensory neurons can determine the pattern of motor output simply by their
      pattern of discharge. This provides a simple form of behavioural selection
      according to stimulus.

PMID- 9190046
TI  - Neural correlates of habituation of the proleg withdrawal reflex in larvae of the
      hawk moth, Manduca sexta.
AB  - The larval proleg withdrawal reflex of the hawk moth, Manduca sexta, exhibits
      robust habituation. This reflex is evoked by deflecting one or more
      mechanosensory planta hairs on a proleg tip. We examined neural correlates of
      habituation in an isolated proleg preparation consisting of one proleg and its
      segmental ganglion. Repeated deflection of a single planta hair caused a
      significant decrease in the number of action potentials evoked in the proleg
      motor nerve (which carries the axons of proleg retractor motor neurons).
      Significant response decrement was seen for interstimulus intervals of 10 s, 60 s
      and 5 min. Response decrement failed to occur in the absence of repetitive
      stimulation, the decremented response recovered spontaneously following a rest,
      and electrical stimulation of a body wall nerve facilitated the decremented
      response (a neural correlate of dishabituation). Adaptation of sensory neuron
      responses occurred during repeated hair deflections. However, when adaptation was
      eliminated by direct electrical stimulation of sensory neurons, the response in
      the proleg motor nerve still decreased significantly. Muscle recordings indicated
      that the response of an identified proleg retractor motor neuron decreased
      significantly during habituation training. Thus, habituation of the proleg
      withdrawal reflex includes a central component that is apparent at the level of a
      single motor neuron.

PMID- 9190048
TI  - Implicit memory effects when using pictures with children and adults: hypermnesia
      too?
AB  - Pictorial stimuli were used to investigate implicit- and explicit-memory
      phenomena in 3 experiments. The general procedure involved the presentation of a
      series of pictures during a study phase, followed by an implicit-memory test and
      an explicit-memory test. In the implicit-memory test, participants were presented
      with picture fragments and were instructed to write down what the fragment looked
      like. In the explicit-memory test, participants were asked to make a yes/no
      recognition decision regarding each picture. For children, implicit memory for
      pictures was robust when they were tested after a 48-hr interval, but that effect
      declined after 1 week; a similar implicit-memory effect for pictures was seen
      with college students; and the time course of the implicit-memory effect for
      pictures among college students (all short intervals of less than 1 week-1, 2, 3,
      4, and 5 days) produced a more elevated implicit-memory performance than during
      the immediate testing condition. Hypermnesia may have been the cause of the
      increase in memory performance over the short intervals.

PMID- 9190049
TI  - Recognition of student names past: a longitudinal study with N = 1.
AB  - Recognition of names of former students taught at different times by a middle
      aged college professor was tested, to investigate recognition memory over a time
      span ranging from 6 months to 26.5 years. The relationship between the d', a
      measure of strength of memory, and the retention interval can be best described
      by a logarithmic function characterized by a rapid initial drop followed by a
      slow forgetting rate. The correct responses (hits and rejections) had higher
      confidence and shorter response time than did the incorrect responses (false
      alarms and misses). The results show that an ecologically realistic longitudinal
      study with N = 1 can provide a valuable means in the study of human memory with
      very long retention intervals, which have not yet been investigated in the
      laboratory.

PMID- 9190050
TI  - Balance and source of social support in relation to well-being.
AB  - Well-being was examined as a function of the balance of provided and received
      levels of four types of social support shared by 165 college students and their
      support networks over 1 semester. Prospective hierarchical regressions of balance
      of support exchange, after controlling for Time 1 level of the dependent
      variable, showed some interactions between hassles level and balance of support
      receipt and provision for symptomatology, but not for depression. These effects
      were stronger for low than for high hassle levels at Time 1 for men, whereas the
      opposite held for women. Men who provided more informational support than they
      received reported more symptoms at Time 2 than did net recipients, if Time 1
      hassles were low. In contrast, women who received more tangible or more
      informational support than they provided at Time 1 reported more symptoms at Time
      2 than did net providers, but only at high hassle levels. Results are interpreted
      in terms of both the costs and the benefits of receiving and providing support.

PMID- 9190051
TI  - The development of gender schemata about heterosexual and homosexual others
      during adolescence.
AB  - Perceptions of heterosexual and homosexual individuals were investigated among 12
      , 16-, and 20-year-old French adolescents. Participants described heterosexual
      and homosexual males and females with typical masculine and feminine personality
      traits. Overall, they perceived heterosexual males as having more masculine
      traits than homosexual males. The 16- and 20-year-olds perceived homosexual males
      as more feminine than heterosexual males, whereas the reverse was observed in 12
      year-olds. Furthermore, the 12-year-olds perceived heterosexual females as more
      feminine than homosexual females, a difference that disappeared in the older age
      groups. Results support the view of early adolescence as a crucial period in the
      development of gender schemata about sexually significant others.

PMID- 9190052
TI  - How you know when you're stressed: self-evaluations of stress.
AB  - One hundred participants were asked to list 5 cues that they use to determine
      their level of stress. The responses were tabulated, and the 25 most frequent
      responses were retained for further analyses. A sorting task was used to assess
      the relationships among cues, and a similarity matrix was developed from the
      responses. This similarity matrix was subjected to cluster analysis. The results
      yielded a taxonomy of cues to stress.

PMID- 9190053
TI  - The role of self-esteem in typical and atypical changes in expectations.
AB  - Self-esteem was explored as a factor in appropriate (typical) and inappropriate
      (atypical) changes in performance expectations across trials of a nonthreatening
      success condition vs. a threatening failure condition. Participants (51 women, 45
      men) were randomly assigned to one of the conditions and completed a self-esteem
      scale and 8 trials of a timed digit-substitution task. Moderated multiple
      regression revealed significant interactions between self-esteem and condition
      for typical and atypical changes. A significant positive relationship between
      self-esteem and typical changes was found under success and between self-esteem
      and atypical changes under failure. Differences between conditions were evident
      only for high self-esteem, with greater typical changes for success and greater
      atypical changes for failure.

PMID- 9190054
TI  - Disgust as the source of false positive effects in the measurement of
      ophidiophobia.
AB  - Why many people who self-report high levels of fear on the Snake Anxiety
      Questionnaire (SNAQ; Klorman, Weerts, Hastings, Melamed, & Lang, 1974) do not
      show subsequent behavioral fear was investigated. Fear and disgust among 70
      female under-graduates were assessed by self-report, behavioral ratings, and
      behavioral approach measures. The results suggest that the observed discordance
      occurs because the SNAQ is strongly confounded by the emotion of disgust.

PMID- 9190055
TI  - Weight fluctuation, bulimic symptoms, and self-efficacy for control of eating.
AB  - College students who reported recent weight fluctuations of 15 pounds represented
      15% of the men (N = 161) and 22% of the women (N = 301) in the study. Comparisons
      were made with students whose weight had remained stable on 4 subscales of the
      Eating Disorders Inventory (Bulimia, Body Dissatisfaction, Drive for Thinness,
      and Interoceptive Awareness), on the Washington Self-Description Questionnaire,
      and on the Situational Appetite Measure. A MANOVA supported gender differences,
      with women showing greater levels of body dissatisfaction and concern for
      thinness. Students whose weight had fluctuated were differentiated from students
      whose weight had been stable, with weight fluctuations being most strongly
      related to greater body dissatisfaction and lower levels of self-efficacy for
      control of eating. Results support the use of a relapse model for weight
      fluctuation, emphasizing the potential importance of low self-efficacy as a
      moderator of repeated weight fluctuation.

PMID- 9190057
TI  - Gender stereotypes: a bias against men.
AB  - In a class on the psychology of male roles, 38 undergraduates (18 men, 20 women)
      participated in an activity designed to assess gender stereotypes. A chi-square
      analysis revealed that participants produced significantly more negative
      stereotypes for men than for women. These results, consistent with crosscultural
      findings, are discussed in terms of methodological issues and the differential
      socialization of men and women.

PMID- 9190058
TI  - Children's attitudes toward violence on television.
AB  - Children's attitudes toward television violence were studied. A 47-item
      questionnaire collecting attitudinal and personal information was administered to
      316 children aged 11 to 16 years. Cluster analysis was used to split the
      participants into two groups based on their attitudes toward television violence.
      A stepwise discriminant function analysis was performed to determine which
      personal characteristics would predict group membership. The only significant
      predictor of attitudes toward violence on television was the amount of television
      watched on school days (p < .05), but we also found that the impact of other
      predictor variables may have been mediated by this factor.

PMID- 9190059
TI  - Task performance of black and white children across levels of presentation
      variability.
AB  - This study is an examination of the task performance patterns of Black and White,
      working and middle-class American children across a nonvaried and a varied
      presentation format condition: the relation of such patterns to activity levels
      in the home and to standardized achievement was also examined. Performance was
      better under the varied than the nonvaried format condition. This pattern held
      for all ethnic group/class combinations with the exception of Black middle-class
      children, for whom performance under the two conditions was virtually identical.
      Moreover, Black children, especially Black working-class children, reported
      greater home activity levels than did their White counterparts. Neither home
      activity level nor achievement was functionally related to patterns of
      performance.

PMID- 9190060
TI  - Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa
      isoforms.
AB  - Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the
      mitochondrial genome and 10 in the nucleus. Little is known of the role of the
      nuclear-encoded subunits, some of which exhibit tissue-specific isoforms. Subunit
      VIa is unique in having tissue-specific isoforms in all mammalian species
      examined. We examined relative evolutionary rates for the COX6A heart (H) and
      liver (L) isoform genes along the length of the molecule, specifically in
      relation to the tissue-specific function(s) of the two isoforms. Nonsynonymous
      (amino acid replacement) substitutions in the COX6AH gene occurred more
      frequently than in the ubiquitously expressed COX6AL gene. Maximum-parsimony
      analysis and sequence divergences from reconstructed ancestral sequences revealed
      that after the ancestral COX6A gene duplicated to yield the genes for the H and L
      isoforms, the sequences encoding the mitochondrial matrix region of the COX VIa
      protein experienced an elevated rate of nonsynonymous substitutions relative to
      synonymous substitutions. This is expected for relaxed selective constraints
      after gene duplication followed by purifying selection to preserve the
      replacements with tissue-specific functions.

PMID- 9190061
TI  - A retrotransposon of the non-long terminal repeat class from the human blood
      fluke Schistosoma mansoni. Similarities to the chicken-repeat-1-like elements of
      vertebrates.
AB  - The genomes of representative species of fishes, amphibians, and reptiles contain
      non-long-terminal-repeat (non-LTR) retrotransposons showing strong sequence
      identity to the chicken repeat 1 (CR1) non-LTR retrotransposon from birds. These
      nonavian retroelements have been termed CR1-like elements. We have isolated
      sequences of a non-LTR retrotransposon from the human blood fluke Schistosoma
      mansoni. These schistosome sequences, which we have termed the SR1 family of non
      LTR retrotransposons, contain regions of deduced amino acids characteristic of
      the CR1-like elements. SR1 elements possess atypical 3' termini consisting of the
      tandem repeat (AACCATTTG)2 which are similar in structure to the imperfect tandem
      repeat of the 3' termini of CR1. There are at least 200 copies of SR1
      interspersed through the genome of S. mansoni. The structural and amino acid
      sequence similarities of SR1 with members of the CR1-like elements suggest that
      the SR1 family belongs to the CR1-like category of non-LTR retrotransposons.
      Although other non-LTR retrotransposons have been described in invertebrates,
      this is the first CR1-like element reported from a nonvertebrate taxon,
      suggesting that the phylogenetic distribution of CR1-like retrotransposons is not
      restricted to vertebrates.

PMID- 9190062
TI  - Color vision of ancestral organisms of higher primates.
AB  - The color vision of mammals is controlled by photosensitive proteins called
      opsins. Most mammals have dichromatic color vision, but hominoids and Old World
      (OW) monkeys enjoy trichromatic vision, having the blue-, green-, and red
      sensitive opsin genes. Most New World (NW) monkeys are either dichromatic or
      trichromatic, depending on the sex and genotype. Trichromacy in higher primates
      is believed to have evolved to facilitate the detection of yellow and red fruits
      against dappled foliage, but the process of evolutionary change from dichromacy
      to trichromacy is not well understood. Using the parsimony and the newly
      developed Bayesian methods, we inferred the amino acid sequences of opsins of
      ancestral organisms of higher primates. The results suggest that the ancestors of
      OW and NW monkeys lacked the green gene and that the green gene later evolved
      from the red gene. The fact that the red/green opsin gene has survived the long
      nocturnal stage of mammalian evolution and that it is under strong purifying
      selection in organisms that live in dark environments suggests that this gene has
      another important function in addition to color vision, probably the control of
      circadian rhythms.

PMID- 9190063
TI  - A molecular phylogeny of the bivalve mollusks.
AB  - A phylogenetic reconstruction based on 506 nucleotides near the 5' end of the 18S
      subunit of ribosomal DNA (rDNA) in 2 gastropod, 3 chiton and 28 bivalve mollusks
      supported the monophyly and sister group relationship of the subclasses
      Heterodonta and Palaeoheterodonta but could not confidently establish either the
      monophyly or the phylogenetic relationships of the morphologically well defined
      subclasses Pteriomorphia, Protobranchia, and Anomalodesmata. When both gastropods
      and chitons were included in the analysis, one or the other invariably emerged
      within Bivalvia. Some evidence indicates that this apparent polyphyly may be the
      consequence of unequal rates of evolution and of rapid changes in the protobranch
      and anomalodesmatan lineages. The taxa usually included in Pteriomorpha emerge as
      a grade rather than a clade, although in a sequence that differs from
      morphologically based phylogenies.

PMID- 9190064
TI  - Evolutionary relationships of sibling tapeworm species (Cestoda) parasitizing
      teleost fishes.
AB  - DNA/DNA hybridization and sequencing of rDNA (partial 18S rDNA and ITS1) were
      used to investigate phylogenetic relationships among seven host-specific
      Bothriocephalus parasites (Cestoda, Pseudophyllidae). The small nucleotide
      divergence between six of the seven bothriocephalids suggests that isolation and
      differentiation of Bothriocephalus lineages in the different host species
      probably occurred recently and over a short time span. Comparison of the
      molecular phylogeny of the parasite species to the phylogeny of their hosts
      (teleostean fishes) revealed little congruence between the branching patterns of
      hosts and parasites, suggesting that bothriocephalids have not cospeciated with
      their hosts.

PMID- 9190065
TI  - Codon bias and plasticity in immunoglobulins.
AB  - Immunoglobulin genes experience Darwinian evolution twice. In addition to the
      germline evolution all genes experience, immunoglobulins are subjected, upon
      exposure to antigen, to somatic hypermutation. This is accompanied by selection
      for high affinity to the eliciting antigen and frequently results in a
      significant increase in the specificity of the responding population. The
      hypermutation mechanism displays a strong sequence specificity. Thus arises the
      opportunity to manipulate codon bias in a site-specific manner so as to direct
      hypermutation to those parts of the gene that encode the antigen-binding portions
      of the molecule and away from those that encode the structurally conserved
      regions. This segregation of mutability would clearly be advantageous; it would
      enhance the generation of potentially useful variants while keeping mutational
      loss to acceptably low levels. But it is not clear that the advantage gained
      would be large enough to produce a measurable effect within the background
      stochasticity of the evolutionary process. I have performed a pair of statistical
      tests to determine whether site-specific codon bias in human immunoglobulin genes
      is correlated with the sequence specificity of the somatic mutation mechanism.
      The sequence specificity of the mutator was determined by analysis of a database
      of published immunoglobulin intron sequences that had experienced somatic
      mutation but not selection. The site-specific codon bias was determined by
      analysis of published sequences of human germline immunoglobulin V genes. Both
      tests strongly suggest that evolution has acted to enhance the plasticity of
      immunoglobulin genes under somatic hypermutation.

PMID- 9190066
TI  - An episodic change of rDNA nucleotide substitution rate has occurred during the
      emergence of the insect order Diptera.
AB  - We have studied the potential reasons for a conspicuous deviation of substitution
      rates in Dipteran ribosomal genes. Systematic pairwise relative-rate tests reveal
      that a significant increase in substitution rate is characteristic for Diptera,
      but not for the other insects analyzed. Estimation of sequence change in specific
      lineages reveals that most of these substitutions took place during the evolution
      of the Dipteran stem lineage. When related to the paleontologically documented
      periods of absolute time, the substitution rate in the stem lineage of the
      Diptera underwent an at least 20-fold increase compared to other insect groups
      and subsequently dropped by a factor of 10 before the diversification of the
      major Dipteran subgroups. Systematic comparisons of nucleotide composition show
      that this episodic change in substitution rate was accompanied by a significant
      increase in A+T content of Dipteran rDNA. Our data suggest that the episodic
      evolution of the Dipteran rDNA has most probably been caused by a change of
      directional mutation pressure which must have occurred during the evolution of
      the stem lineage of the Diptera.

PMID- 9190067
TI  - Rapid evolution in a conserved gene family. Evolution of the actin gene family in
      the sea urchin genus Heliocidaris and related genera.
AB  - Camarodont sea urchins possess a rapidly evolving actin gene family whose members
      are expressed in distinct cell lineages in a developmentally regulated fashion.
      Evolutionary changes in the actin gene family of echinoids include alterations in
      number of family members, site of expression, and gene linkage, and a dichotomy
      between rapidly and slowly evolving isoform-specific 3' untranslated regions. We
      present sequence comparisons and an analysis of the actin gene family in two
      congeneric sea urchins that develop in radically different modes, Heliocidaris
      erythrogramma and H. tuberculata. The sequences of several actin genes from the
      related species Lytechinus variegatus are also presented. We compare the features
      of the Heliocidaris and Lytechinus actin genes to those of the the actin gene
      families of other closely related sea urchins and discuss the nature of the
      evolutionary changes among sea urchin actins and their relationship to
      developmental mode.

PMID- 9190068
TI  - Nucleotide polymorphism in colicin E2 gene clusters: evidence for nonneutral
      evolution.
AB  - To explore the molecular mechanisms behind the diversification of colicin gene
      clusters, we examined DNA sequence polymorphism for the colicin gene clusters of
      14 colicin E2 (ColE2) plasmids obtained from natural isolates of Escherichia
      coli. Two types of ColE2 plasmids are revealed, with type II gene clusters
      generated by recombination between type I ColE2 and ColE7 gene clusters. The
      levels and patterns of DNA polymorphism are different between the two types. Type
      I polymorphism is distributed evenly along the gene cluster, while type II
      accumulates polymorphism at an elevated rate in the 5' end of the colicin gene.
      These differences may be explained by recombinational origins of type II gene
      clusters. The pattern of divergence between the ColE2 gene cluster and its close
      relative ColE9 is not correlated with the pattern of polymorphism within ColE2,
      suggesting that this gene cluster is not evolving in a neutral fashion. A
      statistical test confirms significant departures from the predictions of
      neutrality. These data lend further support to the hypothesis that colicin gene
      clusters may evolve under the influence of nonneutral forces.

PMID- 9190069
TI  - Marmoset phylogenetics, conservation perspectives, and evolution of the mtDNA
      control region.
AB  - Marmosets (genus Callithrix) are a diverse group of platyrrhine primates with 13
      15 purported taxa, many of them considered endangered. Morphological analyses
      constitute most of the basis for recognition of these forms as distinct taxa. The
      purpose of this study was to provide a molecular view, based on mitochondrial
      control region sequences, of the evolutionary history of the marmosets,
      concomitant with a molecular phylogenetic perspective on species diversity within
      the group. An additional purpose was to provide the first comparative examination
      of a complete New World monkey control region sequence with those of other
      mammals. The phylogenetic analyses provide convincing support for a split between
      the Atlantic forest and Amazonian marmosets, with the inclusion of the pygmy
      marmoset (Cebuella pygmaea) at the base of the Amazonian clade. The earliest
      branch of the Atlantic forest group was C. aurita. In the Amazonian group, the
      analyses do not support the recognition of C. humeralifer and the recently
      described C mauesi as distinct taxa. They do, however, support a clear
      distinction between C. argentata and a strongly supported mixed clade of C.
      humeralifer and C. mauesi. In the Atlantic forest group, the phylogenetic tree
      suggests mixing between C. penicillata, C. kuhli, and possibly C. jacchus. Most
      of the sequence features characteristic of other mammal control regions were also
      evident in marmosets, with the exception that conserved sequence blocks (CSBs) 2
      and 3 were not clearly identifiable. Tandem repeat units often associated with
      heteroplasmy in a variety of other mammals were not evident in the marmoset
      sequences.

PMID- 9190070
TI  - Helping heartache.

PMID- 9190071
TI  - Xenotransplantation.

PMID- 9190072
TI  - Effects of fluid shear stress on gene regulation of vascular cells.
AB  - Hemodynamic forces such as fluid shear stress play an active role in many
      physiological and pathophysiological processes of the cardiovascular system.
      Shear stress resulting from blood flow and transmural plasma flux alters the
      function of vascular cell (primarily endothelial cells), leading to both rapid
      and slower adaptive tissue responses. Transmission of the shear stress signal
      throughout the vascular cell involves a complex interplay between cytoskeletal
      and biochemical elements and results in changes in structure, metabolism, and
      gene expression. Herein we review current knowledge on flow-induced
      mechanotransduction in the vascular endothelial cell and the molecular mechanisms
      believed responsible for shear-induced endothelial and smooth muscle cell gene
      regulation with an emphasis on signal transduction.

PMID- 9190073
TI  - Biochemical engineering analysis of critical process factors in the biomass-to
      ethanol technology.
AB  - Ethanol from cellulosic biomass is a promising renewable liquid transportation
      fuel. Applied research in the area of biomass conversion to ethanol in the last
      20 years has answered most of the major challenges on the road to
      commercialization but, as with any new technology, there is still room for
      performance improvement. A verified mathematical model was used to examine the
      most critical biochemical engineering aspects of ethanol production in this
      study. Extensive simulations of the simultaneous saccharification and
      fermentation (SSF) of cellulose were conducted to identify the effects of
      operating conditions, pretreatment effectiveness, microorganism parameters, and
      enzyme characteristics on ethanol production. The results clearly show that the
      biomass-enzyme interaction plays a dominant role in determining the performance
      of SSF in batch and continuous operating modes. In particular, the digestibility
      of the substrate (as a result of pretreatment) and the cellulase enzyme dosage,
      specific activity, and composition had a profound effect on ethanol yield. This
      investigation verified the conclusion that R&D emphasis should be placed on
      developing more effective pretreatment methods and producing cellulase
      preparations of high specific activity (low cost per enzyme unit) to realize
      gains from any development of advanced hexose/pentose-fermenting organisms.

PMID- 9190074
TI  - Ultrasound stimulates ethanol production during the simultaneous saccharification
      and fermentation of mixed waste office paper.
AB  - The commercial production of ethanol from cellulose by simultaneous
      saccharification and fermentation (SSF) is prevented in part by the high cost of
      fungal cellulase enzymes. Intermittent exposure of SSF processes to ultrasonic
      energy under selected conditions (5 FPU of cellulase/g of substrate; 15 min of
      exposure/240 min cycle during the latter half of SSF) was found to increase
      ethanol production from mixed waste office paper by approximately 20%, producing
      36.6 g/L ethanol after 96 h (70% of the maximum theoretical yield). Without
      ultrasound, 10 FPU of cellulase/g of substrate was required to achieve similar
      results. Continuous exposure of the organism to ultrasonic energy was
      bacteriostatic and decreased ethanol production but may be useful for the
      controlling bacterial growth in other processes.

PMID- 9190075
TI  - Enhanced production of human mini-proinsulin in fed-batch cultures at high cell
      density of Escherichia coli BL21(DE3)[pET-3aT2M2].
AB  - Synthesis of recombinant protein (human mini-proinsulin) is investigated in fed
      batch cultures at high cell concentration of recombinant Escherichia coli
      BL21(DE3)[pET-3aT2M2]. Transcription of the recombinant gene is controlled by a
      T7 promoter system. The human mini-proinsulin is characterized by a C-chain
      peptide consisting of only nine amino acids, whereas the C-chain peptide of
      natural human proinsulin is made up of 35 amino acids. It is expressed in a
      fusion protein with a small fusion partner (a peptide with 18 amino acids) and
      finally aggregated into insoluble inclusion bodies in cytoplasm of recombinant E.
      coli. The fermentative production of this small fusion mini-proinsulin may be of
      great advantage in enhancing the yield of human insulin. To find an optimum
      induction strategy, effects of various key cultivation variables on the mini
      proinsulin production are examined in high cell density fed-batch cultures. No
      general correlation is found between preinduction specific growth rate and
      recombinant protein synthesis, which confers a flexibility in choosing the
      feeding strategy of preinduction media for achieving the high cell density
      cultures. A culture temperature below 37 degrees C is unfavorable for recombinant
      gene expression, and the T7-based expression system is almost completely
      repressed at 30 degrees C. The nutrient glucose and yeast extract concentration
      in postinduction feed media is optimized by applying a statistical method for
      medium optimization, i.e. response surface methodology, and an effective amount
      of inducer molecule (IPTG) is determined to maximize the specific recombinant
      protein formation. The mini-proinsulin production in E. coli culture is
      significantly influenced by the volumetric feed rate of postinduction media,
      which is shown to be closely related to the plasmid copy number in the
      recombinant cell. Consequently, in a single-stage fed-batch process, the mini
      proinsulin concentration is increased up to 7 g/L, approximately 62 wt % of which
      corresponds to mature human insulin. A two-stage fed-batch fermentation process,
      with recombinant cell growth occurring at a constant growth rate and constant
      cell concentration in a growth fermenter and mini-proinsulin production in an
      induction fermenter, is designed, and its efficacy in increasing volumetric
      productivity of mini-proinsulin is demonstrated.

PMID- 9190076
TI  - Continuous enzymatic hydrolysis of beta-casein and isoelectric collection of some
      of the biologically active peptides in an electric field.
AB  - Among the milk proteins, bovine beta-casein has the peculiarity of containing in
      its sequence some peptides liable to interfere in mineral nutrition and some
      peptides with opioid (casomorphines), antihypertensive, and immunomodulatory
      activities. In this work we propose a novel type of multicompartment enzyme
      reactor, operating under an electric field, for the continuous hydrolysis of milk
      proteins such as beta-casein. The enzyme trypsin is trapped, with zwitterionic
      buffering ions and its substrate beta-casein, in solution between two isoelectric
      membranes having pI values encompassing the isoelectric point of the enzyme.
      Additionally, beta-casein is captured inside the same reaction chamber with the
      aid of sieving membranes, since its pI is too far away from the pI of trypsin.
      This setup permits the continuous operation at the pH of optimum of activity. The
      peptides, arising from tryptic hydrolysis of beta-casein, are removed under the
      influence of the electric field and collected in different chambers in which they
      are isoelectric and isoionic as well. The purity of the peptides collected is
      ascertained by capillary zone electrophoresis and their identity confirmed by N
      terminal sequencing and MALDI-TOF mass spectrometry. This setup allows continuous
      harvesting of some biologically-active peptides in a pure form. The major
      advantages of such a reactor system over conventional batch reactors are the
      great increase in enzyme utilization efficiency and the overall reactor
      productivity.

PMID- 9190077
TI  - Adsorption behavior of multicomponent protein mixtures containing alpha 1
      proteinase inhibitor with the anion exchanger, 2-(diethylamino)ethyl-Spherodex.
AB  - The equilibrium binding behavior of alpha 1-proteinase inhibitor (alpha 1-PI) in
      the presence of human serum albumin (HSA) has been determined in packed bed
      systems with the anion exchanger, 2-(diethylamino)ethyl (DEAE)-Spherodex.
      Experimental data derived for the individual proteins were compared with the
      corresponding data obtained from batch adsorption studies as well as studies in
      which mixtures of these two proteins were loaded at different concentration
      ratios onto columns of the same anion exchange adsorbent. The results confirm
      that alpha 1-PI has a greater affinity for the anion exchanger, although
      competitive adsorption was observed as the inlet concentration of HSA was
      increased. Under these conditions, decreased binding capacities and lower dynamic
      adsorption rates were observed for alpha 1-PI with the DEAE-Spherodex anion
      exchange adsorbent. The results are discussed in terms of the influence which
      various contaminants that occur in multicomponent mixtures of proteins from human
      plasma can have on the equilibrium binding characteristics of a target protein
      with weak or strong ion exchange adsorbents under conditions approaching
      concentration overload in preparative chromatographic systems. These
      investigations have also addressed, as the first part of an iterative approach
      for the simulation of the adsorption behavior of multicomponent mixtures of human
      plasma proteins with ion exchange and affinity chromatographic adsorbents, the
      ability of noncompetitive and competitive Langmuirean models to simulate the
      adsorption of alpha 1-PI in the presence of different concentrations of HSA to
      DEAE-Spherodex.

PMID- 9190079
TI  - Preparative concentration and size fractionation of DNA by porous media using a
      combination of flow and low electric field strength.
AB  - The retention of DNA by porous media during chromatography with an applied axial
      electric field was investigated. DNA was retained by negative electric fields in
      columns packed with Sephadex G-75 and G-25. A negative field was defined as the
      electric field orientation in which the direction of electrophoresis was opposing
      the direction of buffer flow (positive electrode at the column inlet). A positive
      field was not effective at retaining the DNA. The electric field strength
      required to retain the DNA was dependent upon the buffer flow rate. The retention
      of DNA using Sephadex G-25, a gel filtration medium with a higher degree of cross
      linking, required higher electric fields than the more porous Sephadex G-75. A
      dilute DNA solution was concentrated at the inlet of the chromatography bed by an
      electric field. Mixtures of DNA restriction fragments were used to determine size
      dependent retention. DNA was size-fractionated by varying the electric field
      strength and flow rate. At a given electric field strength and flow rate, the
      lower molecular weight DNA fragments were not as strongly retained as the higher
      molecular weight fragments. Decreasing the flow rate or increasing the electric
      field strength resulted in increased retention of the lower molecular weight DNA
      fragments. In this manner, by selecting a specific set of conditions (packing
      material, flow rate, and electric field strength), the molecular weight of DNA
      fragments retained by the column can be adjusted. Efficient separation of high
      molecular weight DNA from bovine serum albumin, a protein with high
      electrophoretic mobility, was demonstrated using a field of 2 V/cm in a column
      packed with Sephadex G-75.

PMID- 9190081
TI  - Effect of oxygen limitations on monoclonal antibody production by immobilized
      hybridoma cells.
AB  - The productivity of an immobilized cell biocatalyst is often limited by the
      amount of oxygen that reaches cells located at interior regions of the
      biocatalyst. These diffusive limitations depend on a multitude of factors
      including the oxygen supply, the cellular uptake kinetics, and the cell density
      of the material. Large cell densities, which are desired for high productivity,
      are also likely to reduce the percentage of cells that receive an adequate supply
      of oxygen. To develop a better understanding of how different conditions affect
      biocatalyst behavior, a computational model of immobilized hybridoma cells was
      developed. The model accounts for oxygen diffusion and consumption, cell
      proliferation and death, and monoclonal antibody production. This model assumes
      that cellular productivity is limited only by the supply of oxygen and that the
      growth media is continually replenished so that nutrient levels remain high and
      wastes are eliminated. Biocatalyst performance is evaluated by monitoring the
      amount of monoclonal antibody produced by the cells. Model predictions agree with
      experimental measurements reported in the literature and indicate that for long
      operation time the supply of oxygen, biocatalyst size, and cell kinetics have a
      significant effect on biocatalyst performance, whereas the initial cell loading
      has only a relatively small effect. Under typical culture conditions, we find
      that oxygen penetrates to a maximum depth of about 0.4 mm. Accordingly, cells
      immobilized farther than this threshold distance receive an insufficient supply
      of oxygen.

PMID- 9190082
TI  - Glycosylation of CHO-derived recombinant tPA produced under elevated pCO2.
AB  - Carbon dioxide is a metabolic byproduct of mammalian cell metabolism that can
      accumulate in poorly ventilated cultures. A buildup of CO2 at constant pH will be
      accompanied by an increase in medium osmolality. We have examined the
      glycosylation of tissue plasminogen activator (tPA) produced under serum-free
      conditions by recombinant Chinese hamster ovary (CHO) cells (MT2-1-8 cell line)
      in response to elevated pCO2 at constant or elevated osmolality. The proportion
      of sialic acids comprising N-glycolylneuraminic acid decreased from 2.3-4.0%
      under 36 mmHg pCO2 to 1.5-2.2% under 250 mmHg pCO2. No changes were observed in
      the total sialic acid content, the content of other monosaccharides, the relative
      amounts of type I and type II tPAs, the distribution of surface charges, or the
      proportion of high-mannose oligosaccharides-even though these conditions have
      previously been shown to inhibit the specific growth rate of MT2-1-8 cells by 30
      40% and the specific tPA production rate by as much as 40%. These results suggest
      robust glycosylation of tPA by CHO cells.

PMID- 9190084
TI  - Folates and one-carbon metabolism in plants and fungi.
AB  - Folate-dependent pathways of one-carbon metabolism are essential for the
      synthesis of purines, formylmethionyl-tRNA, thymidylate, serine and methionine.
      These syntheses use a cellular source of one-carbon substituted, tetrahydrofolate
      polyglutamate derivatives which are the preferred substrates of most folate
      dependent enzymes. In the last decade, there have been major advances in the
      folate biochemistry of animal, bacterial, fungal and plant systems. These have
      included the refinement of methods for folate isolation and characterization,
      basic work on key enzymes of folate biosynthesis and the detailed
      characterization of proteins that catalyze the generation and utilization of one
      carbon substituted folates.

PMID- 9190085
TI  - Cytotoxic prenylated flavanones from Monotes engleri.
AB  - From the leaves of Monotes engleri, five prenylated flavanones were isolated as
      constituents that displayed cytotoxic activity against several human cancer cell
      lines. There of these substances are novel, namely, 6-(1,1
      dimethylallyl)naringenin, 6-(1,1-dimethylallyl)eriodictyol and 3'-O-methyl-6-(1,1
      dimethylallyl)-eriodictyol, with the other two active substances being the known
      flavanones, 6,8-diprenyleriodictyol and hiravanone. Additionally, two novel, but
      non-cytotoxic, biogenetically related flavanones were isolated, 6-[(2RS)-hydroxy
      3-methyl-3-butenyl]-8-prenyleriodictyol and 5,4'-dihydroxy-4",4"-dimethyl-5"
      methyl-5"H-dihydrofurano[2",3": 6,7]flavanone. The structures of the new
      compounds were determined by spectral analysis 1D- and 2D-NMR experiments.

PMID- 9190086
TI  - Nonprotein amino acids from Cycas revoluta.
AB  - Two nonprotein amino acids, cycasindene and cycasthioamide, along with eight
      known nonprotein amino acids, were isolated from the seeds of Cycas revoluta
      Thunb. The structures of cycasindene and cycasthioamide were elucidated as 3-[3'
      amino-indenyl-2]-alanine (1) and N-[glycinyl-alaninyl-11-thio]-5-one-pipecolic
      acid (2) by chemical and spectral methods.

PMID- 9190087
TI  - Clerodane diterpenoids, long chain esters of coumaric acid and other compounds
      from Baccharis myrsinites.
AB  - A new clerodane diterpenoid and two new long chain esters of trans- and cis
      coumaric acid, in addition to known triterpenoids and one known clerodane
      diterpenoid, have been isolated and characterized from Baccharis myrsinites. The
      structures were determined by spectroscopic techniques.

PMID- 9190088
TI  - [Cartilaginous tumors of the cricoid: imaging diagnosis. A case report].
AB  - Cartilaginous tumors of the larynx are rare; although chondromas are the most
      frequent of these tumors. Laryngeal chondrosarcomas are even rarer, in spite of
      this being the most frequent histological variety of sarcoma (less than 1% of all
      malignant laryngeal tumors). These tumors are slow-growing, locally aggressive,
      and tend to recur. They are less aggressive in the larynx than in other sites:
      cervical or distant metastases are rare (8.5%) and recurrences often can be
      controlled. The most common presenting symptom is hoarseness with normal indirect
      laryngoscopy. The complementary studies of choice are computed tomography (CT)
      and magnetic resonance imaging (MRI). The role of these imaging techniques in the
      study of laryngeal chondroma and chondrosarcoma was examined. These sporadic
      tumors may be overlooked, although early identification is necessary for
      effective treatment.

PMID- 9190089
TI  - Case reports: invasive Haemophilus influenzae type a infections.

PMID- 9190090
TI  - Cognitive-behavioral interventions to manage depression in patients with cancer:
      research and theoretical initiatives.
AB  - The incidence of depression is rising worldwide, possibly due to urban crowding
      and insufficient resources. This pandemic raises the possibility that disabling
      depression among patients with cancer will increase. Already, about one-third of
      patients with cancer present with depression. Although many progressive cancer
      centers are instituting psychooncology services, the projected decline in numbers
      of psychiatrists in the coming decade suggests that these programs may flounder
      unless nurses are able to provide adjuvant support. Consequently, this article
      describes the theoretical and emerging research data base regarding the treatment
      of cancer-related depression with cognitive-behavioral therapy. Implications
      drawn from this review suggest that nurses can take an active role in preventing
      and managing cancer-related depression in direct care environments by developing
      critical pathways for screening, prevention, treatment, and outcomes assessment
      using theory-based research.

PMID- 9190091
TI  - Diagnosis and treatment of major depression among people with cancer.
AB  - Although depressive disorders are common among 20-25% of people with cancer, they
      are frequently unrecognized. Untreated depression in the presence of comorbid
      conditions may result in more frequent clinic visits, increased costs, extended
      hospitalization, and reduced compliance and quality-of-life. Oncology clinicians
      need not have psychiatric expertise to play a major role in the detection and
      treatment of depression and in the prevention of suicide. Using early detection
      and screening tools, the nurse can identify depressed patients and can
      collaborate in their treatment. Approximately 80-90% of depressed patients are
      effectively treated with psychotherapy, and/or pharmacologic, or somatic,
      interventions. Failure to diagnose or reluctance to treat depression among
      patients with cancer is a common error and can increase morbidity and mortality.

PMID- 9190092
TI  - Exploring the psychosocial meaning of recurrent cancer: a descriptive study.
AB  - Many persons diagnosed with malignancy will experience one or more recurrences of
      malignancy. Little is known about the psychosocial meaning of recurrent cancer.
      Using Lazarus and Folkman's model of stress, appraisal and coping, the two
      purposes of this descriptive study were to (a) describe the meaning of a
      recurrence of cancer to the patient and (b) to explore if the patient perceives
      the diagnosis of recurrence as being different from the initial diagnosis of
      cancer. Purposeful sampling for persons with recent recurrent malignancy produced
      a sample (n = 20). Subjects completed an unstructured, indepth interview. The
      meaning of the recurrence was influenced by prior cancer-related experiences of
      the subjects and dominated by death and death-related concerns. Differences from
      the initial diagnosis included a deeper awareness of the significance of the
      "cancer diagnosis".

PMID- 9190093
TI  - Empowerment of men newly diagnosed with prostate cancer.
AB  - The purpose of this study was to explore the hypothesis that assisting men with
      prostate cancer to obtain information would enable them to assume a more active
      role in treatment decision making and decrease their levels of anxiety and
      depression. Respondents were recruited from one community urology clinic in
      Winnipeg, Manitoba. Sixty newly diagnosed men were randomly assigned to receive
      either a self-efficacy information intervention that consisted of a written
      information package with discussion, a list of questions they could ask their
      physician, and an audiotape of the medical consultation (n = 30), or a written
      information package alone (n = 30). Men completed measures of preferred
      decisional role as the pretest; anxiety and depression before the intervention,
      and at 6 weeks post-intervention; and assumed decisional role at 6 weeks post
      intervention. Results demonstrated that men in the intervention group assumed a
      significantly more active role in treatment decision making, and had lower state
      anxiety levels at 6 weeks. Levels of depression were similar for both groups at 6
      weeks. This group of older men do want to be informed and participate in medical
      decisions. Further efforts are required to evaluate the efficacy of such an
      intervention in other community urology clinics.

PMID- 9190094
TI  - Current review of cancer nursing in Hong Kong.

PMID- 9190095
TI  - Nurses' knowledge about equianalgesia and opioid dosing.
AB  - Nurses are recognized as the cornerstone of palliative care. Yet, surveys of
      nurses' knowledge of cancer pain management reveal serious knowledge deficits
      that could adversely affect the care of patients with cancer pain. Previous
      research has explored basic pain management issues such as pain assessment and
      myths and misconceptions surrounding pain, and principles of analgesic use.
      Advances in recent years have increased the demand for continuing education that
      will extend scientific advances in pain to clinical practice. The purpose of this
      article is to share results from a study which evaluated nurses knowledge
      regarding three methods of analgesic delivery that have become common in clinical
      practice: intravenous morphine, extended release morphine, and transdermal
      fentanyl. Several resources are provided to assist clinicians in the appropriate
      use of these analgesic methods.

PMID- 9190096
TI  - The genetic basis of cancer.

PMID- 9190097
TI  - Lateral pharyngeal wall motion during swallowing using real time ultrasound.
AB  - B-mode ultrasound imaging has been used primarily to detect temporal and spatial
      movements of the tongue during the oral preparatory and oral stages of
      swallowing. The purpose of this study was to investigate the application of M
      mode (motion mode) ultrasound imaging as a method to quantify the duration and
      displacement of single regions along the lateral pharyngeal wall during swallows
      of two bolus volumes and during three swallow maneuvers (supraglottic, super
      supraglottic and Mendelsohn maneuver). In 5 normal subjects, simultaneous B/M
      mode images were captured at two regions along the lateral pharyngeal wall.
      Computer-assisted video analysis of each swallow sequence provided spatial
      coordinates and durational measures. Results indicated no significant differences
      in displacements of the lateral pharyngeal wall across bolus volumes, swallow
      maneuvers, or recording sites. Significant differences (p < 0.001) in lateral
      pharyngeal wall duration occurred as a function of volitional swallow maneuvers.
      Greater durations (p < 0.05) were found for the Mendelsohn and super-supraglottic
      swallow maneuvers. The data demonstrate that B/M-mode ultrasound imaging provides
      a simple, noninvasive method to visually examine movements of the lateral
      pharyngeal wall and may provide a clinical method for assessing the effects of
      direct swallowing therapies at the level of the mid-oropharynx.

PMID- 9190098
TI  - Predictors of outcome following cricopharyngeal disruption for pharyngeal
      dysphagia.
AB  - The indications for, and predictors of outcome following cricopharyngeal
      disruption in pharyngeal dysphagia are not clearly defined. Our purpose was to
      examine the symptomatic response to cricopharyngeal disruption, by either myotomy
      or dilatation, in patients with oral-pharyngeal dysphagia and to determine pre
      treatment manometric or radiographic predictors of outcome. Using simultaneous
      pharyngeal videoradiography and manometry, we studied 20 patients with pharyngeal
      dysphagia prior to cricopharyngeal dilatation (n = 11) or myotomy (n = 8), and 23
      healthy controls. We measured peak pharyngeal pressure, hypopharyngeal intrabolus
      pressure, upper esophageal sphincter diameter, and coordination. Response rate to
      sphincter disruption was 65%. The extent of sphincter opening was significantly
      reduced in patients compared with controls (p = 0.004), but impaired sphincter
      opening was not a predictor of outcome. Increased hypopharyngeal intrabolus
      pressures (> 19 mmHg for 10 ml bolus; > 31 mmHg for 20 ml bolus) was a
      significant predictor of outcome (p = 0.01). Neither peak pharyngeal pressure nor
      incoordination were predictors of outcome. In pharyngeal dysphagia,
      hypopharyngeal intrabolus pressure, and not peak pharyngeal pressure, is a
      predictor of response to cricopharyngeal disruption. The relationship between
      intrabolus pressure and impaired sphincter opening is an indirect measure of
      sphincter compliance which helps predict therapeutic response.

PMID- 9190099
TI  - Dysphagia in progressive supranuclear palsy: radiologic features.
AB  - Progressive supranuclear palsy (PSP) is a progressive degenerative extrapyramidal
      disease that often masquerades as Parkinson's disease (PD). Similar to PD,
      dysphagia frequently complicates the course of PSP. Because there is only one
      published report characterizing dysphagia in PSP, we reviewed the neurologic
      features and dynamic videofluoroscopic swallowing function study results in 10
      dysphagic PSP patients. Abnormalities during multiple stages of ingestion were
      recorded in each patient. Uncoordinated lingual movements, absent velar
      retraction or elevation, impaired posterior lingual displacement, and copious
      pharyngeal secretions were noted in all patients. Tongue-assisted mastication,
      noncohesive lingual transfer, excessive oral bolus lingual leakage to the pharynx
      prior to active transfer, vallecular bolus retention, abnormal epiglottic
      positioning, and hiatal hernias were noted in at least half of the cohort.
      Although ingestion abnormalities in PSP are similar to those previously reported
      in PD, the number of studied patients and observed differences were too few to
      clearly differentiate the two diseases.

PMID- 9190100
TI  - The role of the insular cortex in dysphagia.
AB  - Recent data indicate that dysphagia may occur following unilateral cortical
      stroke; however, the elucidation of specific cytoarchitectonic sites that produce
      deglutition disorders remains unclear. In a previous study of unilateral cortical
      stroke patients with dysphagia, Daniels et al. proposed that the insula may be
      important in swallowing as it was the most common lesion site in the patients
      studied. Therefore, 4 unilateral stroke patients with discrete lesions of the
      insular cortex were studied to further facilitate understanding of the role of
      the insula in swallowing. Dysphagia, as confirmed by videofluoroscopy, was
      evident in 3 of the 4 patients; all had lesions that involved the anterior
      insula, whereas the only patient without dysphagia had a lesion restricted to the
      posterior insula. These data suggest that the anterior insula may be an important
      cortical substrate in swallowing. The anterior insula has connections to the
      primary and supplementary motor cortices, the ventroposterior medial nucleus of
      the thalamus, and to the nucleus tractus solitarius, all of which are important
      regions in the mediation of oropharyngeal swallowing. Therefore, discrete lesions
      of the anterior insula may disrupt these connections and, thereby, produce
      dysphagia.

PMID- 9190101
TI  - Incomplete upper esophageal sphincter relaxation: association with achalasia but
      not other esophageal motility disorders.
AB  - Incomplete upper esophageal sphincter (UES) relaxation is not well understood. We
      compared clinical and manometric characteristics of patients with normal and
      abnormal UES relaxation. Consecutive patients (n = 208) underwent manometric
      evaluation of the lower esophageal sphincter (LES), esophageal body, and
      UES/pharynx. The patients were divided into those with abnormal UES relaxation
      (residual pressure > 6.7 mmHg) (n = 21) and normal relaxation (n = 187). Clinical
      and manometric profiles were compared. Sex, age, and presenting complaint did not
      correlate with UES relaxation. Normal esophageal peristaltic sequences were more
      frequently present in the normal UES group (73.6%) compared with the abnormal
      (55.8%) (p < 0.01). The UES relaxation was shorter in the group with abnormal
      relaxation (410.0 ms vs. 510.2 ms, p < 0.001). All other manometric parameters
      were not different between the two groups. When individual manometric diagnoses
      were analyzed, only achalasia was noted to be more common in the abnormal UES
      group (23.8% vs. 9.1%, p < 0.05), and a trend was noted toward diffuse esophageal
      spasm being more common (14.3% vs. 9.6%, not significant). We conclude that
      incomplete UES relaxation is a rare manometric finding, associated with achalasia
      and not specifically associated with any other motility disturbance. This finding
      may represent a secondary response to the poor esophageal emptying seen in
      achalasia.

PMID- 9190102
TI  - A pilot exploratory study of oral electrical stimulation on swallow function
      following stroke: an innovative technique.
AB  - This pilot study investigated the effect of oral electrical stimulation on
      swallow function in stroke patients with chronic dysphagia. The purpose was to
      determine whether an innovative technique could make an improvement in swallow
      function that might be developed as a potential treatment for patients with
      persistent dysphagia. Four stroke patients with chronic dysphagia were recruited
      on the basis of videofluoroscopic findings of a delayed swallow reflex. A single
      case design was used. Oral electrical stimulation of swallowing was carried out
      using a palatal prosthesis starting at an output pulse of 0.5 mA, with a fixed
      duration of 200 microsec, repeated at 1-sec intervals. Barium paste (1 x 5 ml)
      was introduced at the level of the patient's maximum tolerance of stimulation and
      any effect on swallow function was recorded by videofluoroscopy. The findings
      from the pilot study indicated that oral electrical stimulation resulted in an
      improvement in swallow function in 2 of the 4 patients. The stimulation was well
      tolerated in all cases with no serious adverse effects. These early results are
      promising, but further research is needed.

PMID- 9190103
TI  - Primary biliary cirrhosis, sicca complex, and dysphagia.
AB  - We investigated symptoms suggestive of swallowing problems in patients with
      primary biliary cirrhosis, some of whom displayed features of sicca complex. A
      prospective study of 95 consecutive patients with primary biliary cirrhosis was
      conducted at a single teaching hospital using a questionnaire administered over
      the telephone. Some symptoms of sicca complex (dry mouth and/or dry eyes) were
      found in 65 patients (68.4%). Subjective xerostomia alone was present in 45
      patients (47.4%). The questionnaire revealed an increase in incidence of
      dysphagia in xerostomia subjects, affecting 21 of 45 patients, compared with 6 of
      50 non-xerostomia patients. Multivariate logistic regression analysis showed that
      confounding factors such as age, obesity, cigarette smoking, and medications
      associated with a dry mouth could not explain these findings. Twenty-eight
      patients complained of hoarseness, 23 of coughing, and 14 of wheezing, all of
      which were significantly more frequent than in the 50 patients without
      xerostomia. Heartburn affected 17 xerostomia patients and 15 non-xerostomia
      patients, indicating no difference in frequency between these two groups, even
      after age, obesity, cigarette smoking, and medications associated with heartburn
      were considered in the multivariate analysis. Acid regurgitation, nausea, and
      vomiting were also similar in frequency between patients with and without
      xerostomia. Swallowing problems, manifested primarily as dysphagia, are common in
      primary biliary cirrhosis patients who have subjective xerostomia.

PMID- 9190104
TI  - Function of the inferior pharyngeal constrictor muscle.

PMID- 9190105
TI  - Nutritional status of patients with amyotrophic lateral sclerosis: relation to
      the proximity of death.

PMID- 9190106
TI  - European Immunologists meet in Amsterdam.

PMID- 9190107
TI  - Antiviral immunity.

PMID- 9190108
TI  - Aspects of lymphocyte developmental biology.

PMID- 9190109
TI  - The Th1/Th2 paradigm.

PMID- 9190110
TI  - Tumor antigens recognized by T cells.

PMID- 9190111
TI  - Destruction of proteins as a creative force.

PMID- 9190112
TI  - CD40-CD40L interactions in atherosclerosis.

PMID- 9190113
TI  - IL-10: a potential therapy for allergic inflammation?

PMID- 9190115
TI  - Immunoreceptor tyrosine-based inhibition motifs.

PMID- 9190114
TI  - Natural anti-Gal antibody as a universal augmenter of autologous tumor vaccine
      immunogenicity.

PMID- 9190116
TI  - TAP off--tumors on.

PMID- 9190117
TI  - Serial triggering of TCRs: a basis for the sensitivity and specificity of antigen
      recognition.

PMID- 9190118
TI  - Dissociation of multivalent antibody-antigen interactions.

PMID- 9190119
TI  - Heritability of adaptive variation: an old problem revisited.

PMID- 9190120
TI  - Training and overtraining: an overview and experimental results in endurance
      sports.
AB  - Overtraining can be defined as "training-competition > > recovery imbalance",
      that is assumed to result in glycogen deficit, catabolic > anabolic imbalance,
      neuroendocrine imbalance, amino acid imbalance, and autonomic imbalance.
      Additional non-training stress factors and monotony of training exacerbate the
      risk of a resulting overtraining syndrome. Short-term overtraining called
      overreaching which can be seen as a normal part of athletic training, must be
      distinguished from long-term overtraining that can lead to a state described as
      burnout, staleness or overtraining syndrome. Persistent performance incompetence,
      persistent high fatigue ratings, altered mood state, increased rate of
      infections, and suppressed reproductive function have been described as key
      findings in overtraining syndrome. An increased risk of overtraining syndrome may
      be expected around 3 weeks of intensified/prolonged endurance training at a high
      training load level. Heavy training loads may apparently be tolerated for
      extensive periods of time if athletes take a rest day every week and use
      alternating hard and easy days of training. Persistent performance incompetence
      and high fatigue ratings may depend on impaired or inhibited transmission of
      ergotropic (catabolic) signals to target organs, such as: (I) decreased
      neuromuscular excitability, (II) inhibition of alpha-motoneuron activity
      (hypothetic), (III) decreased adrenal sensitivity to ACTH (cortisol release) and
      increased pituitary sensitivity to GHRH (GH release) resulting in a counter
      regulatory shift to a more anabolic endocrine responsibility, (IV) decreased beta
      adrenoreceptor density (sensitivity to catecholamines), (V) decreased intrinsic
      sympathetic activity, and (VI) intracellular protective mechanisms such as
      increased synthesis of heat-shock proteins (HSP 70) represent a complex strategy
      against an overload-dependent cellular damage.

PMID- 9190122
TI  - The influence of muscle group location and race on the relationship between
      muscle strength and power.
AB  - OBJECTIVE: This study investigated the influence of muscle group location and
      racial background on the relationship between measures of muscle strength and
      power. It was hypothesized that both African American (AA) and Caucasian American
      (CA) males would exhibit similar strength-power relationships, but these
      relationships would be dependent upon muscle group location. EXPERIMENTAL DESIGN:
      A cross-sectional, comparative design was used. SETTING: The Human Performance
      Laboratory at the U. of Oklahoma. SUBJECTS: Normal, healthy college-aged AA (n =
      14) and CA (n = 15) males volunteered for this study. MEASURES: Upper and lower
      body strength (IRM) was assessed using a Smithpress bench press and Polaris leg
      press, and upper and lower body power was measured with a piezoresistive
      accelerometer. RESULTS: When comparing power between upper and lower body muscle
      groups, both AA and CA groups exhibited similar relationships (r = 0.68 and r =
      0.61, respectively), however, the relationship between upper and lower body
      strength was relatively stronger for the AA group (r = 0.65 vs r = 0.42). When
      evaluating the strength-power relationship within a given muscle group, i.e.,
      upper or lower body, there were no racial differences, but the relationship
      between strength and power did differ with respect to muscle group location.
      CONCLUSIONS: There were stronger relationships between measures of muscular
      strength and power for the lower limbs when compared to the upper body indicating
      the importance of muscle group location rather than racial ethnicity as a
      confounding factor that can affect neuromuscular force production. This
      information is important when attempting to characterize neuromuscular function
      relative to specific skills or motor sport performance, thus emphasizing the
      principle of specificity.

PMID- 9190121
TI  - Interpreting energy expenditure for anaerobic exercise and recovery: an anaerobic
      hypothesis.
AB  - Energy expenditure during and after exercise is composed of aerobic and anaerobic
      bioenergetics and the energy demands of aerobic recovery. Current attempts to
      measure energy expenditure include an exercise oxygen uptake + oxygen debt (EPOC)
      measurement or, an oxygen deficit + exercise oxygen uptake measurement. This
      investigation illustrates how oxygen debt and oxygen deficit interpretation can
      effect a total energy expenditure measurement. It was hypothesized that the total
      energy expenditure for several intermittent bouts of exercise and recovery would
      be greater than for one bout of continuous exercise and recovery when equivalent
      work was compared. Exercise was performed under low-intensity and high-intensity
      conditions. Both oxygen debt and oxygen deficit methodology resulted in similar
      energy expenditure measurements for both intermittent and continuous exercise.
      This implies little to no recovery energy demand or considerable methodology
      errors. Differences in total energy expenditure were found when the oxygen
      deficit and parts of the oxygen debt (EPOC) were considered separate and
      independent (p < 0.05). These differences can be accounted for when the data are
      interpreted utilizing thermodynamic (2nd law) and engineering (in-series
      efficiency) concepts rather than the heat equivalent of carbohydrate oxidation
      (20.9 kJ equals one liter of O2). It is suggested that while oxygen uptake
      provides an excellent representation of aerobic metabolism during exercise and
      recovery, oxygen uptake may be an inadequate measure of the energetics of lactate
      production (fermentation). In application, energy expenditure differences appear
      realistic only for high-intensity, intermittent exercise rather than lower
      intensity exercise.

PMID- 9190123
TI  - The effect of exercise induced glycogen depletion on the lactate, ventilatory and
      electromyographic thresholds.
AB  - BACKGROUND: This study compared the integrated electromyogram (IEMG), lactate,
      and ventilatory thresholds under normal glycogen (NG) and depleted glycogen (DG)
      conditions for the purpose of determining the presence of a possible relationship
      between neuromuscular, metabolic and respiratory thresholds. MATERIALS AND
      METHODS: Six trained, male cyclists (Age = 24.0 +/- 2.45 yrs, Ht = 1.76 +/- 0.84
      m, Mass = 76.22 +/- 10.03 kg, % Fat = 8.57 +/- 1.50, VO2 peak = 68.97 +/- 10.46
      ml . kg-1 . min-1) completed a progressive, incremental cycle ergometer test
      under NG and DG conditions in a randomized order. Glycogen depletion was
      accomplished by having the subjects: (1) engage in a 12 hour fast prior to the
      exercise test, (2) complete a 1.5 hour ride at their ventilatory threshold, and
      (3) complete 4 to 8 one-minute rides at 100% of VO2 peak. Six hours following the
      depletion rides, the subjects completed the exercise test (90 rpm, 45 watts/2
      min). Blood was withdrawn through a forearm venous catheter each minute and later
      analyzed for blood lactate. Metabolic data were measured every 30s and the IEMG
      of the rectus femoris was recorded during the last 10s of each minute of the
      exercise test. Results showed that under NG, the IEMG (TIEMG), lactate (Tlac),
      and ventilatory (Tvent) thresholds occurred at a similar VO2 (TIEMG = 3.46 +/-
      0.31, Tlac = 3.51 +/- 0.34, Tvent = 3.36 +/- 0.42 L . min-1). However, under DG
      there was a significant shift in the TIEMG to a higher VO2 (TIEMG = 4.41 +/- 0.54
      L . min-1 = p 0.003). Tlac was not significantly greater following glycogen
      depletion, but had shifted to a higher VO2 in relation to the Tvent (Tlac = 3.96
      +/- 0.40 L . min-1, Tvent = 3.37 +/- 0.64 L . min-1 = p 0.01). These data show
      that lactate accumulation and muscle activation of the vastus lateralis and
      rectus femoris are not the controlling mechanisms of the ventilatory threshold
      during progressive, incremental cycling exercise.

PMID- 9190124
TI  - Physical performance of elite New Zealand Olympic class sailors.
AB  - OBJECTIVE: The purpose of this study was to compare the physical performance of
      elite New Zealand and other nations olympic class sailors and to undertake an
      initial examination of the relation between physical and sailing performance.
      EXPERIMENTAL DESIGN: A comparative study. SETTING: Healthy elite national level
      olympic class sailors were examined. PARTICIPANTS: Thirty-one elite New Zealand
      Olympic sailing squad team members and 108 Olympic team sailors from ten other
      nations. INTERVENTIONS: The data for the two groups of subjects was compared
      using unpaired "t"-tests. A qualitative analysis was used to examine the relation
      between physical and sailing performance. MEASURES: Measurements included age,
      body mass, muscular strength endurance (as assessed by the maximum number of push
      ups, pull-ups and sit-ups that could be performed) and serobic power (as assessed
      by the time taken to cover 2500 m and the distance completed in 12 minutes in a
      maximal effort rowing ergometer test). Sailing performance was assessed by
      national coach ranking of each New Zealand sailor. RESULTS: On average the New
      Zealanders were younger and lighter than the sailors from the other nations. They
      tended to have greater shoulder/arm strength endurance as reflected in their
      performance for push-ups and pull-ups, but a lesser ability in their sit-up
      performance. They also tended to be aerobically fitter. There were clear and
      logical differences between body mass and both class of vessel and the position
      of the sailor i.c. crew or helmsman. Lighter sailors sailed lighter craft whilst
      heavier sailors sailed the heavier craft. Crew members were generally heavier
      than helmsmen. Age appeared to be related to sailing performance. CONCLUSIONS:
      Elite New Zealand Olympic class sailors tend to be younger, lighter, stronger and
      aerobically fitter than elite sailors from other nations. Age appeared to be
      related to on-water sailing performance.

PMID- 9190125
TI  - Comparison of the testosterone-to-cortisol ratio values obtained from hormonal
      assays in saliva and serum.
AB  - Testosterone (T) and cortisol (C) were determined in serum and saliva, sampled
      simultaneously, from triathletes and karate athletes, in order to determine the
      T:C ratios in those body fluids and the relationship between them, as well as to
      assess the salivary T:C ratio as a measure of the so-called anabolic-catabolic
      index. Mean salivary T:C (value (1.67 +/- 0.85) was nearly 3-fold lower than that
      obtained for serum (4.87 +/- 1.86). Salivary and serum values were strongly
      correlated with one another (r = 0.874, p < 0.001) but the relationship depended
      on the range of cortisol concentrations in serum, the slope of the salive-serum
      regression line being significantly lower for serum cortisol concentrations over
      600 nmol.l-1 than for concentrations below that value (0.305 and 0.380, p < 0.05,
      respectively). It has been concluded that the salivary T:C ratio, based on values
      reflecting the levels of biologically active fractions of T and C in circulation,
      is a better measure of metabolic equilibrium conditioned by those hormones than
      the corresponding ratio obtained from total concentrations in serum.

PMID- 9190126
TI  - Salivary cortisol response to a 30 mn submaximal test adjusted to a constant
      heart rate.
AB  - BACKGROUND: The aim of this study was to analyse the salivary cortisol variations
      during a 30 min sub-maximal exercise, the load being fitted so that the heart
      rate remains constant at 170 +/- 4 bpm. METHODS: Tests were conducted at 10 a.m.
      precisely (in order to avoid circadian variations), and cortisol values were
      recorded every 5 mn by means of a sampling collector over 40 mn), (30 mn bout +
      10 mn post-exercise) and then at 30 mn, 1 h 30 mn and 5 h following the end of
      the exercise. Test values were compared to reference values, (average cortisol
      resting levels obtained at comparable hours on a previous day). Nine sport
      students, (5 boys, 4 girls) entered the study. RESULTS: The cortisol level
      presented a significant increase from the first step of the exercise and then, as
      opposed to an exercise where a constant load is applied, it did not keep
      increasing but remained steady until the end of the test. After stopping, a new
      significant increase surprisingly appeared; the values then dropped to reference
      levels, but they were still higher 1h 30 mn after exercise had stopped.
      CONCLUSIONS: It appears that when the perceived stress of the body reaches an
      equilibrium, as controlled by monitoring the heart rate, cortisol levels quickly
      rise to a steady state, about two folds higher than resting values in our
      experimental conditions.

PMID- 9190127
TI  - Effect of lactic acid on water content and osmotic fragility of erythrocytes in
      vivo.
AB  - OBJECTIVE: A coll planet centrifuge is an apparatus for the dynamic measurement
      of erythrocyte osmotic fragility, and it was applied to the observation of
      altered erythrocyte osmotic fragility induced by the lactic acid. Changes in
      intracellular water content of red cells were also measured according to the
      method, based on gas-liquid chromatography. EXPERIMENTAL DESIGN: Blood was
      withdrawn from the animal by cardiac puncture before and after lactic acid
      injection. The lactic acid was injected to rabbit through the auricular vein till
      the final concentration for the circulating blood was 0.7 mg/ml. RESULTS: The
      water content in the red cells before the lactic acid injection was between
      71.37% and 73.33%. It increased after the lactic acid injection and reached the
      maximum of 102% of the original content. Hemolysis of erythrocytes before the
      injection of lactic acid began at 108.3 to 110.3 mOsm and ended at 77.0 to 81.0
      mOsm, and after the injection it began at 117.0 to 120.7 mOsm and ended at 84.5
      to 87.3 mOsm. CONCLUSIONS: In the present experiment the decrease in pH of the
      blood in lactic acid administered rabbits was too small to cause any changes in
      the osmotic fragility, suggesting that changes of the erythrocyte membrane
      properties, owing to the presence of lactic acid in the blood had occurred.

PMID- 9190128
TI  - Changes in central motor-sensory system following voluntary movement of
      stimulated finger.
AB  - OBJECTIVE: We examined which components of somatosensory evoked potentials (SEP)
      were modulated during the voluntary movement of stimulated fingers and discuss
      our findings with respect to the decrease in SEPs in terms of both centrifugal
      and centripetal mechanisms. METHODS: The study was performed in the Laboratory of
      Physiology, Institute of Health and Sport Sciences, University of Tsukuba.
      Experiments were performed on 10 healthy young male subjects, aged 19-21 years.
      All subjects were right-handed and were free of neurological disease. RESULTS: We
      found that N20-P25 (P22 at frontal area) -N35-(N30 at frontal) P45 (P40 at
      frontal area) components at the F3, the C3' and the P3 were consistently evoked,
      but N35 was increased at P3 and N30 attenuation at F3 during a sustained
      voluntary movement. Furthermore, the present experiments showed that frontal N30
      was markedly decreased during a sustained voluntary movement. We also found that
      all SEPs components, except for parictal N35, were significantly decreased during
      sustained voluntary movement tasks. CONCLUSIONS: We concluded that the
      suppression of SEPs appeared to be due to the interaction of both centrifugal and
      centripatal mechanisms. Namely, in a particular type of movement task, more
      prenounced afferent mechanisms may contribute to the decrease in SEPs, while in
      the other types of tasks, more pronounced afferent activities may contribute to
      the decrease in SEPs.

PMID- 9190129
TI  - Low intensity physical training in older subjects.
AB  - BACKGROUND: This study was designed to evaluate the effects of a low intensity
      general training program (< 50% of heart rate reserve) on physical fitness of
      healthy older subjects, by comparing maximal and submaximal indices of training
      response. METHODS: Twenty-two volunteers over 60 years of age participated in the
      present study. The sample was randomly divided in an experimental group of 13
      older subjects (3 men and 10 women, mean age 63.5 +/- 3 years) while the
      remaining 9 subjects (3 men and 6 women, mean age 64.2 +/- 4 years) served as
      inactive control group. After medical screening all participants were evaluated
      before and after 12 weeks in which the experimental subjects underwent a low
      intensity training. Each subjects-either inactive or active-performed two
      treadmill tests at two-days interval, to measure maximal and submaximal responses
      to exercise, respectively. Heart rate (HR), oxygen uptake (VO2) and pulmonary
      ventilation (VE) were measured using a telemetric apparatus. RESULTS: The major
      finding of the study was the significant improvement in submaximal response to
      exercise of experimental subjects, expressed by the reduction in HR, VO2 VE while
      VO2 max did not change. CONCLUSIONS: Thus, it appears that a low intensity
      general training similar to that followed in the present study may represent a
      good means to improve physical fitness in healthy elderly people. Similarly, this
      study supports the effectiveness of evaluation tests based on submaximal
      responses to exercise in this population.

PMID- 9190131
TI  - Wanted: 1,289 practice opportunities.

PMID- 9190130
TI  - Applying physiological principles and assessment techniques to swimming the
      English Channel. A case study.
AB  - BACKGROUND: This study presents the use of physiological principles and
      assessment techniques in addressing four objectives that can enhance a swimmer's
      likelihood of successfully swimming the English Channel. The four objective were:
      (1) to prescribe training intensities and determine ideal swimming pace; (2) to
      determine the amount of insulation needed, relative to heat produced, to diminish
      the likelihood of the swimmer suffering from hypothermia; (3) to calculate the
      caloric expenditure for the swim and the necessary glucose replacement required
      to prevent glycogen depletion; and (4) to determine the rate of acclimatization
      to cold water (15.56 C/60 F). METHODS: The subject participated in several pool
      swimming data collection sessions including a tethered swim incremental protocol
      to determine peak oxygen consumption and onset of lactate accumulation and
      several steady state swims to determine ideal swimming pace at 4.0 mM/L of
      lactate. Additionally, these swims provided information on oxygen consumption,
      which in combination with ultrasound assessment of subcutaneous fat was used to
      assess heat production and insulation capabilities. Finally, the subject
      participated in 18 cold water immersions to document acclimatization rate.
      RESULTS: The data demonstrated the high fitness level of this subject and
      indicated that at a stroke rate of 63 stokes/min, HR was 130 heats/min and
      lactate was 4 mM/L. At this swimming pace the swimmer would need to consume 470
      kcal of glucose/hr. In addition, the energy produced at this swim pace was 13.25
      kcal/min while the energy lost at the present subcutaneous fat quantity was 13.40
      kcal/min, requiring a fat weight gain of 6,363.03 g (13.88 lbs) to resist heat
      loss. CONCLUSIONS: Finally, the data from the cold water immersions suggested
      that acclimatization occurred following two weeks of immersions. There results
      were provided to the swimmer and utilized in making decisions in preparation for
      the swim.

PMID- 9190132
TI  - The sacred trust.

PMID- 9190133
TI  - Role of indocyanine green fluorescence videoangiography in evaluation of
      subretinal disease.
AB  - BACKGROUND: Indocyanine green (ICG) is a sterile, water-soluble, tricarbocyanine
      dye that can be used in fundus angiography as an adjunct to sodium fluorescein.
      It has a peak spectral absorption of 805 nm in blood plasma or blood, as compared
      with fluorescein, which has a peak spectral absorption of 465 nm. Because the
      absorption and emission of ICG lies around 835 nm, transmission of energy by the
      retinal pigment epithelium (RPE) and serosanguinated material is more efficient
      in this region than in the region of visible light energy. ICG has the property
      of being approximately 98% bound to blood protein, disallowing extravasation of
      excessive dye in the highly fenestrated choroidal vasculature. METHODS: The
      characteristics of ICG are discussed, including administration and dosage,
      adverse reactions and use of infrared filters for fundus photography. In
      addition, two cases are presented to illustrate the clinical application of ICG
      for diagnosis and treatment of choroidal neovascular membranes. RESULTS: ICG
      videoangiography can be used to reveal subfoveal choroidal neovascular membranes
      not previously identified with fluorescein; angiograms can also be used to
      dramatically highlight retinal and choroidal changes. CONCLUSIONS: The use of ICG
      for fundus videoangiography provides a more accurate and complete evaluation in
      certain cases of subretinal and choroidal disease.

PMID- 9190134
TI  - Effects of yellow optical filters on contrast sensitivity function of albino
      patients.
AB  - BACKGROUND: Yellow ophthalmic filters are often prescribed for albino patients in
      an effort to enhance visual performance. The effects of a moderate- and a high
      excitation purity yellow filter on the contrast sensitivity function (CSF) of ten
      albino patients were investigated. Hue discrimination loss induced by each filter
      was also evaluated. METHODS: Three monocular CSF curves (best-corrected eye) were
      determined for each subject: one while viewing through a #3 Kodak Wratten filter,
      one through a #12 filter, and one used no filter. Panel D-15 color tests were
      administered to five albino patients viewing through each filter. RESULTS: Using
      an analysis of variance (ANOVA) and a Student-Newman-Keuls Analysis, no
      statistical difference at the 0.05 levels of confidence was found between using
      no filter, the #3 filter, or the #12 filter CSF curves. A statistically
      significant blue-yellow hue confusion was induced by the #12 filter. CONCLUSIONS:
      While neither filter was shown to enhance nor degrade the CSF among these
      subjects, a more extensive investigation may reveal that subtle but real contrast
      enhancement occurs with yellow filter use. High-purity filters should be avoided
      to minimize hue recognition losses.

PMID- 9190135
TI  - Visual performance and patient preference: a comparison of anti-reflection coated
      and uncoated spectacle lenses.
AB  - BACKGROUND: Anti-reflection (AR) coatings of spectacle lenses are designed to
      reduce the reflected images often found in uncoated lenses. This study examined
      the visual impact of a specific AR coating. METHODS: First, using a survey, it
      was determined if patients were aware of the AR coating and, if given an
      identical pair of lenses without the AR coating, which lenses were preferred and
      why. Second, in the laboratory, changes in visual performance were evaluated when
      an anti-reflection coating was applied to a lens. RESULTS: Verbal reports were
      obtained from 18 patients on both types of lenses. All patients were aware the AR
      coating reduced unwanted reflections, and many reported reductions in visual
      problems associated with glare. Within the laboratory, 28 patients were tested on
      a battery of clinical vision tests. Under normal room illumination, visual
      acuity, grating-contrast sensitivity, and letter-contrast sensitivity were
      identical for both coated or uncoated lenses. In a second experiment, the effects
      of AR coating on contrast sensitivity were examined when subjects viewed a dimly
      illuminated target while their eye and face were brightly illuminated. Under
      these conditions, significantly better (a factor of two) contrast sensitivity was
      observed with AR-coated lenses. CONCLUSIONS: On the basis of these findings, it
      is proposed that drivers should wear AR-coated spectacle lenses at night.

PMID- 9190136
TI  - Contact lens correction of patients with Marfan syndrome.
AB  - BACKGROUND: Marfan syndrome, a genetic connective tissue disorder, manifests many
      problems: high myopia, astigmatism, crystalline lens subluxation, and cataracts.
      No published studies have described the contact lens corrections that can be used
      with Marfan syndrome patients. This report describes the variety of contact lens
      modalities used for a subpopulation of patients with Marfan syndrome. METHODS:
      The clinical records of eight patients with Marfan syndrome (16 eyes) from two
      hospital-based contact lens practices were retrospectively reviewed. Seven
      different contact lens modalities were used for this subpopulation. RESULTS: Mean
      unaided visual acuities were 20/296, while mean best-corrected optimal spectacle
      refraction visual acuities were 20/33. Contact lenses improved the mean visual
      acuity to 20/27. Patients wore the contact lenses for an average of 12 hours per
      day. Complications of contact lens wear occurred in approximately 70% of eyes and
      included neovascularization, giant papillary conjunctivitis, 3 and 9 o'clock
      staining, and central superficial punctate staining. Additionally, ocular non
      contact lens-related complications occurred in 50% of patients. CONCLUSIONS: A
      variety of contact lens designs may be used during the care of patients with
      Marfan syndrome. However, patients may experience an increased rate of
      complications associated with contact lens wear or unrelated to lens wear, and
      thus they deserve more intensive follow-up care than non-Marfan syndrome
      patients.

PMID- 9190137
TI  - Torpedo maculopathy.
AB  - BACKGROUND: Congenital nevi of the retinal pigment epithelium (RPE) may manifest
      variable degrees of pigmentation. These nevi, which are almost always
      asymptomatic, can be either solitary or grouped. Torpedo maculopathy is a
      recently described congenital RPE nevus. METHODS: A review of congenital nevi of
      the RPE is presented to include torpedo maculopathy. RESULTS: Torpedo maculopathy
      is a solitary congenital RPE nevus; it is oval, variably pigmented, and located
      in the temporal macula. Diagnosis of this lesion is made on the basis of its
      characteristic shape and location. The etiology may be related to alterations in
      the choroidal vasculature in the macular area during the embryologic development
      of the eye. Because of the benign nature of the nevus, yearly evaluations are
      recommended. CONCLUSIONS: Classification of congenital nevi of the RPE is still
      evolving. As more is learned, a better system of organizing these lesions will be
      developed.

PMID- 9190138
TI  - Migraine-related visual-field loss with prolonged recovery.
AB  - BACKGROUND: Migraine is a complex neurologic syndrome that commonly causes visual
      disturbances. Although migraine visual disturbances are usually transient in
      nature, persistent or permanent visual field defects may occur. When persistent
      visual-field loss is found-even if migraine is suspected-appropriate workup must
      be performed to rule out other causes of vision loss. CASE REPORTS: Two patients
      went to the eye clinic for comprehensive examination. One patient with
      symptomatic visual loss and one patient with asymptomatic visual loss were
      evaluated by serial ophthalmic examinations, neurologic/medical evaluations,
      computed tomography of the head, and laboratory results. Each patient reported a
      history consistent with migraine, and each demonstrated resolution of persistent
      visual-field defects that had been present longer than 10 days. Since ophthalmic,
      medical, laboratory, and imaging results did not identify and etiology other than
      migraine as the cause of the vision loss, it is likely that each case represents
      a specific form of complicated migraine. CONCLUSIONS: Previous reports suggest
      that migraine-related visual deficits usually become permanent if persistent for
      more than 7 days. These reports demonstrate that visual recovery may still occur
      when field defects are present for 10 days or more.

PMID- 9190139
TI  - Glaucoma--a clinicolegal review.
AB  - BACKGROUND: Glaucoma is a leading cause of professional liability claims
      involving eye care practitioners. Reasons for litigation include the severe loss
      of vision that can result if the disease goes undetected and the variety of legal
      theories-breach of informed consent, negligence, and product liability-under
      which a practitioner may be held liable. METHODS: Leading cases and claims are
      reviewed to describe the variety of clinical situations in which glaucoma-related
      lawsuits have been successfully alleged. RESULTS: Eye care practitioners are most
      likely to be charged with failure to diagnose open-angle glaucoma, but failure to
      warn patients of suspicious findings and adverse effects of antiglaucoma
      medications are also significant causes of liability claims.

PMID- 9190140
TI  - Effects of long-term treatment with lansoprazole and omeprazole on serum gastrin
      and the fundic mucosa.
AB  - OBJECTIVE: To compare the effects of long-term lansoprazole and omeprazole
      treatment (6 months) on serum gastrin levels. PATIENTS: Forty duodenal ulcer
      patients without previous treatment with proton pump inhibitors were randomized
      to receive either 20 mg/day or omeprazole or 30 mg/day of lansoprazole. Serum
      gastrin levels were determined on entry and every 2 months. On finalizing the
      study antral and fundic biopsies were obtained for immunohistochemical analysis
      of the enterochromaffin-like cell population. RESULTS: Before starting the
      treatment fasting serum gastrin was similar in both groups (108.7 +/- 60.9 pg/mL
      omeprazole; 102.7 +/- 56.9 pg/mL lansoprazole). The treatment with either
      omeprazole or lansoprazole increased serum gastrin levels, but the increase was
      mild, maximal at 2 months and similar between omeprazole and lansoprazole (113.44
      +/- 114.9 pg/mL omeprazole vs 166.1 +/- 117.9 pg/mL lansoprazole; p > 0.05). When
      serum gastrin levels were individually analyzed by patient, most were below 200
      pg/mL and only 3 patients (1 omeprazole/2 lansoprazole) had levels near 500 pg/mL
      which were not correlated with enterochromaffin-like cell hyperplasia.
      CONCLUSIONS: Long-term treatment with either omeprazole or lansoprazole is safe,
      at least during 6 months, and results in mild hypergastrinemia. No differences
      between these two drugs were observed.

PMID- 9190141
TI  - Seasonal influence in exacerbations of inflammatory bowel disease.
AB  - Several epidemiological studies have suggested a possible seasonality in the
      presentation and course of inflammatory bowel disease. Our aim was to investigate
      whether in our area there is a seasonality in the presentation and evolution of
      inflammatory bowel disease. In this retrospective evaluation 255 patients were
      included, of whom 141 patients were diagnosed with ulcerative colitis and 114
      with Crohn's disease according to conventional criteria, with histological
      confirmation in 225 patients. Relapse was defined as the development of symptoms
      that required an increase or change in the usual treatment. Periods of activity
      were related to the month and grouped within one of four seasonal periods:
      December to February, March to May, June to August and September to November.
      Bouts of ulcerative colitis and Crohn's disease were most frequently diagnosed in
      the period June to August (p < 0.05). Both diseases showed similar seasonality,
      and analysis of the 305 attacks did not show any significant trend. In
      conclusion, inflammatory bowel disease begins more frequently in the period June
      to August, but its course does not show consistent seasonal variations.

PMID- 9190142
TI  - Treatment of achalasia with botulinum toxin.
AB  - We studied the efficacy of local injections of botulinum toxin in the treatment
      of patients with achalasia. Four patients diagnosed of achalasia using
      manometric, radiologic and endoscopic criteria, were treated with botulinum toxin
      (80 U) injected directly into lower esophageal sphincter (LES), via a
      sclerotherapy injector. Response to treatment was assessed by changes in symptom
      scores and LES pressure. All determinations were repeated after 10, 30, 90, 120
      and 180 days of treatment. The patients improved after the initial injection.
      This improvement was accompanied by improved relaxation of the LES. Two patients
      relapsed after 30 and 65 days and the other two patients remained symptom-free 5
      months after treatment. CONCLUSION: Botulinum toxin is probably a safe and
      effective alternative for the treatment of achalasia and should be considered in
      patients in whom pneumatic dilation has failed or who are poor surgical
      candidates. Long-term evaluation of the safety and efficacy of botulinum toxin in
      the treatment of achalasia is required.

PMID- 9190143
TI  - Combined small bowel and reduced liver transplantation in pigs.
AB  - PURPOSE: Small bowel transplantation is a last resort treatment for intestinal
      insufficiency. Although the disorder is occasionally associated with chronic
      hepatopathy of variable severity, it may require simultaneous liver
      transplantation. We present a new model of heterotopic small bowel and reduced
      partial liver transplantation to an infrahepatic site. SUBJECTS AND METHODS:
      "Mini-pig" breed pigs weighing 28 to 35 kg were divided into four experimental
      transplant groups: intestine only (IO) without immunosuppression (group 1A, n =
      11); IO with immunosuppression (group 1B, n = 10); intestine + reduced liver
      (IRL) without immunosuppression (group 2A, n = 12); IRL with immunosuppression
      (group 2B, n = 10). RESULTS: Overall mortality from technical causes (first 3
      days) was 23/43 animals (53.4%). All animals in group 1A displayed rejection,
      which was the main cause of death. Rejection occurred in 1 animal in each of the
      other three groups. CONCLUSIONS: Heterotopic small bowel-reduced liver transplant
      is a multivisceral model that has the technical advantage of not requiring
      hepatectomy, and the immunological advantages of delayed appearance of acute
      rejection and the possibility of reducing immunosuppression during the first
      postoperative days.

PMID- 9190144
TI  - Above the glass ceiling? A comparison of matched samples of female and male
      executives.
AB  - In this study the authors compare career and work experiences of executive women
      and men. Female (n = 51) and male (n = 56) financial services executives in
      comparable jobs were studied through archival information on organizational
      outcomes and career histories, and survey measures of work experiences.
      Similarities were found in several organizational outcomes, such as compensation,
      and many work attitudes. Important differences were found, however, with women
      having less authority, receiving fewer stock options, and having less
      international mobility than men. Women at the highest executive levels reported
      more obstacles than lower level women. The gender differences coupled with
      women's lower satisfaction with future career opportunities raise questions about
      whether women are truly above the glass ceiling or have come up against a 2nd,
      higher ceiling.

PMID- 9190145
TI  - Support for affirmative action, justice perceptions, and work attitudes: a study
      of gender and racial-ethnic group differences.
AB  - Do gender and race-ethnicity moderate people's reactions to perceptions that
      their organization supports affirmative action/equal opportunity (AA/EO)? This
      study compared relationships between perceptions of support for AA/EO,
      distributive and procedural justice, career development opportunities, and work
      attitudes in 4 groups of federal employees: White men (n = 4,919), White women (n
      = 1,622), Blacks/Hispanics (n = 492), and Asians (n = 195). Surprisingly, White
      men did not associate support for AA/EO with a loss in career development
      opportunities, organizational injustice, or negative work attitudes. For women
      and racial-ethnic minorities, support for AA/EO was positively linked to
      perceptions of organizational justice and increased career development
      opportunities. As predicted, Blacks/Hispanics had more positive reactions than
      other employee groups. We conclude that support for AA/EO is generally viewed as
      fair and has positive attitudinal consequences.

PMID- 9190146
TI  - A test of the influence of goal orientation on the feedback-seeking process.
AB  - A longitudinal field study (N = 44) and a scenario study (N = 239) were conducted
      to investigate the influence of the individual difference of goal orientation (an
      orientation toward developing or demonstrating one's ability) on feedback-seeking
      behavior by the inquiry method. The results of the 2 studies were consistent with
      the hypotheses of a positive relationship between a learning-goal orientation and
      feedback seeking and of a negative relationship between a performance-goal
      orientation and feedback seeking. Also as hypothesized, the perceived cost and
      perceived value of feedback seeking mediated these relationships. The theoretical
      and practical implications of the research are discussed.

PMID- 9190147
TI  - Job-related and psychological effects of sexual harassment in the workplace:
      empirical evidence from two organizations.
AB  - Previous evidence regarding the outcomes of sexual harassment in the workplace
      has come mainly from self-selected samples or analogue studies or those using
      inadequate measures. The sexual harassment experiences, coping responses, and job
      related and psychological outcomes of 447 female private-sector employees and 300
      female university employees were examined. Discriminant function analyses
      indicated that women who had not been harassed and women who had experienced low,
      moderate, and high frequencies of harassment could be distinguished on the basis
      of both job-related and psychological outcomes. These outcomes could not be
      attributed to negative affective disposition, attitudes toward harassment, or
      general job stress. Results suggest that relatively low-level but frequent types
      of sexual harassment can have significant negative consequences for working
      women.

PMID- 9190148
TI  - Reaction time and assessments of cognitive effort as predictors of eyewitness
      memory accuracy and confidence.
AB  - The authors investigate reaction time, subjective assessments of memory
      processing, and confidence as predictors of memory for the details of a crime.
      The authors also examine the mediation of a previously identified difference
      between recognition tasks and recall tasks in the correlation between confidence
      and accuracy. College undergraduates (n = 111) answered either recognition or
      recall questions. Reaction time and subjective assessments of cognitive effort
      were both negatively related to confidence and accuracy. Subjective assessments,
      however, were superior predictors of confidence, whereas reaction time was a
      unique predictor of accuracy. The reaction time-confidence and reaction time
      accuracy correlations were stronger under recall conditions than under
      recognition conditions. Multiple regression results suggested a possible
      explanation for the superior insight of recall participants into memory accuracy.

PMID- 9190149
TI  - [The syncytial effect of herpes virus.I--Action of UV-inactivated viruses on
      rabbit renal cell monolayers].

PMID- 9190150
TI  - [Virologic and serologic study on subjects vaccinated with Sabin vaccine, living
      in a community].

PMID- 9190151
TI  - [Adenovirus 9 nosocomial infection].

PMID- 9190153
TI  - [Ultrastructure of bacterial fimbriae in E. coli and Sh. flexneri].

PMID- 9190152
TI  - [Sinusitis in ducklings caused primarily by a serologically filtrable agent
      related to N virus (Dinter, 1949)].

PMID- 9190155
TI  - [Applicability of passive cutaneous anaphylaxis test (Ovary) to the study of
      toxoplasmosis].

PMID- 9190154
TI  - [Ultrastructural features of Entamoeba histolytica. Electron microscopy studies].

PMID- 9190156
TI  - [Base composition of deoxyribonucleic acids in L. plantarum].

PMID- 9190158
TI  - Megatrials.

PMID- 9190157
TI  - [The problem of toxin and virus migration along the nervous trunks].

PMID- 9190159
TI  - Osteoporosis: highlights from recent conferences.

PMID- 9190160
TI  - [The laryngeal mask--an expanding concept in airway safety].

PMID- 9190161
TI  - [Craniosynostosis operations in childhood].
AB  - Premature osteosynthesis of one or more cranial bones, either intrauterine or
      within the first postnatal months, is defined as craniosynostosis. The resulting
      limitation of intracranial space can cause retardation of cranial growth which,
      in turn, leads to craniostenosis with increasing intracerebral pressure. Complex
      forms of craniosynostosis with concomitant malformations (i.e. Apert-, Crouzon-,
      and Pfeiffer syndromes) must be principally distinguished from simple
      craniosynostosis. This complex cranio-facial dysostosis is a premature
      osteosynthesis of cranial and facial bones. In general, as far as Germany is
      concerned, the incidence of cranio-synostosis amounts to 1/1000 births. If they
      remain untreated, many of these children will suffer from cortex-associated
      retardation of intelligence. Surgical management, therefore, is initiated at a
      very early stage, and should be performed in specialised centres. Recommendations
      for operation vary from an age of 4 to 36 months. However, an age of 6 months or
      more is the most frequently preferred age for surgical intervention. Severe
      respiratory disorders, as well as impossibility of enteral intake of nourishment,
      are considered absolute indications for surgery, independent of the age;
      elimination of the stigmatisation regarding environmental contacts of the child
      is another mandatory indication for operation. The goal of early surgery is
      reconstruction of physiological, cranial, and facial bone structures ("fronto
      orbital" or "fronto-facial advancement"). Correction of craniofacial malformation
      may be associated with--in part--severe complications for the child. From the
      anaesthesiologist's point of view, this disease demands highly qualified
      perioperative management, since a variety of idiosyncrasies and risks must be
      taken into account: These are, for example, venous air embolism, hypothermia,
      disorders of water and electrolyte equilibrium, and, extremely vital, difficult
      intubation and substantial blood loss.

PMID- 9190162
TI  - [Experiences with use of the laryngeal mask with flexible, wire reinforced tube
      for ENT interventions in childhood].
AB  - This is a report on experiences regarding the use of the reinforced laryngeal
      mask airway for 121 minor operations in paediatric otolaryngology. By far the
      most interventions were adeno-tonsillectomies (104), which until now were
      performed under general anaesthesia with tracheal intubation. RESULTS: The rate
      of observed complications was surprisingly low. 117 children were able to undergo
      their operation using the laryngeal mask airway. Tracheal intubation became
      necessary four times (failure to bring laryngeal mask into position occurred
      twice, laryngospasm occurred once, cough/pressing caused by lack of adequate
      depth of anaesthesia in two cases). In five cases there were problems of
      ventilation (4.1%), provoked by the Boyle-Davis gag. Seven children complained of
      postoperative sore throat, a complication that could be avoided later by
      measuring the cuff pressure (25-70 cm H2O). Aspiration was not observed in any of
      the cases. The complete absence of choking or pressing was regarded as
      particularly favourable by both the anesthetist and the surgeon. CONCLUSION: The
      use of the reinforced laryngeal mask airway during paediatric otolaryngological
      operations in the hand of an experienced anaesthetist appears to be a promising
      alternative to tracheal intubation and merits more widespread use.

PMID- 9190163
TI  - [Use of the laryngeal mask in adenoidectomy in childhood--a comparison with
      endotracheal intubation].
AB  - PURPOSE: Anaesthesia for adenoidectomy is possible during infancy without
      succinylcholine. One possibility is intubation with vecuronium bromide, whereas
      another possibility is the use of the laryngeal mask (LMN). The conditions for
      intubation as well as further details during anaesthesia are listed and compared.
      METHODS: 200 children are divided into 4 groups. Group A: intubation with
      thiopental and vecuronium bromide. Group B: LMN with thiopental, Group C and D:
      as A and B but the thiopental replaced by propofol. The following aspects are
      compared: the conditions of intubation; circulation conditions; oxygen
      saturation; the behaviour when coming out of anaesthesia; complications; the
      assessment by the surgeons. A further control of 100 routine LMN covers the
      complications which arose. RESULTS: Adenoidectomy can be carried out successfully
      with both kinds of anaesthesia. Tracheal intubation attained a better assessment
      by most surgeons and is easier to administer. Brief declines in the saturation of
      oxygen occur more frequently when using LMN. LMN has its advantages in the low
      irritation of the respiratory mucous membranes and results in improved behaviour
      on coming out of the anaesthesia, especially if used with propofol. Problems
      arise mainly through the use of the mouth clamp which can result in obstructions
      of the respiratory tract and re-intubation. These problems arise less frequently
      when the use of this method has become routine. CONCLUSION: LMN takes time to get
      used to, and places greater demands on the anaesthetist. Success of LMN depends
      on the cooperation and collaboration to the surgeon to lower the risk of
      complications. Once specific improvements in the LMN have been made, it may
      become the standard method for adenoidectomy in future. It is already used by us
      and in some outpatient departments, as well as in England and America. Our
      suggestions are as follows: Aims at convincing the surgeons and improving their
      co-operation; No routine fixation of the laryngeal mask. The laryngeal mask
      should be kept slightly taut before opening--preferably slowly--the mouth clamp;
      possible technical modifications of the mouth clamp itself, which produce a wider
      gap, could be adapted to the new conditions of the wider LM; reaching the
      necessary depth of anaesthesia through higher doses of propofol or possibly by
      total intravenous anaesthesia; routine wearing of the LM in the recovery room
      until it is no longer tolerated by the child.

PMID- 9190164
TI  - [Fiber optic intubation using a modified laryngeal mask. Report of experiences
      with use in 105 patients].
AB  - PURPOSE: This study was made to investigate the suitability of a modified
      laryngeal mask airway as an aid for fibreoptic endotracheal intubation in
      patients with a difficult airway. We used a laryngeal mask airway split
      lengthwise on its convex site, the incision going from a point corresponding to
      the teeth down to the base of the cuff. The cuff remains uncut. By this
      modification it is possible to ventilate an anaesthetised patient and to pass
      down a fibreoptic bronchoscope via splitting of the laryngeal mask airway into
      the trachea at the same time. An endotracheal tube of any diameter already
      mounted over the bronchoscope is then guided into the trachea. The feasibility of
      this technique was tested and haemodynamic reactions and changes of the
      parameters of respiration were recorded. METHODS: This technique was used in 105
      patients, 68 male and 37 female, mean age 34 years, when difficult intubation was
      expected or occurred. Blood pressure, pulse rate and peripheral oxygen saturation
      was recorded on arrival in the anaesthetic room, after induction of anaesthesia,
      during and after fibreoptic endotracheal intubation. The respiratory minute
      volume was measured after insertion of the laryngeal mask airway and during the
      course of fibreoptic intubation. The time needed was recorded. RESULTS: In all
      cases endotracheal intubation was successful using this technique. The time
      needed was between 4 and 16 minutes. There was a statistically significant
      increase in peripheral oxygen saturation and decrease of the pulse rate after
      induction of anaesthesia. There were no further significant changes of the
      recorded haemodynamic parameters and the oxygen saturation during and after
      fibreoptic intubation compared to the results after induction of anaesthesia.
      CONCLUSION: It could be demonstrated that a fibreoptic intubation is possible in
      cases of a difficult airway using the technique described here. There is no
      haemodynamic strain on the patient. This method can be carried out without
      pressure of time and without to endanger the patient by hypoxia as the patient
      can be ventilated during the fibreoptic intubation. In cases of impossible
      intubation and insufficient mask ventilation it can be tried to establish
      ventilation and to avoid a emergency surgical airway or transtracheal jet
      ventilation by using this technique.

PMID- 9190165
TI  - [Risks and side effects of diagnostic bronchoalveolar lavage in ventilated
      patients].
AB  - Bronchoalveolar lavage is used increasingly often as a diagnostic tool in
      critically ill patients undergoing mechanical ventilation. Most patients, even
      those with haemodynamic instability or respiratory failure, tolerate the
      procedure without marked adverse effects. A relatively small proportion of
      patients, however, will experience potentially deleterious side effects like
      prolonged deterioration of pulmonary mechanics, oxygen desaturation or sepsis
      like symptoms. Despite all precautions, it is not possible to date to identify
      increased-risk patients beforehand. The potential benefits, namely, early
      diagnosis of an aetiological agent who is responsible for infection, must
      therefore be carefully weighted against the risks.

PMID- 9190166
TI  - [Medico-legal aspects of anesthesia and intensive care medicine. 1: The treatment
      error].

PMID- 9190167
TI  - [Severe aspiration pneumonia with the laryngeal mask].
AB  - The anaesthesia management of a 10-year old girl with a fracture to her distal
      arm is presented, using inhalational anaesthesia with a laryngeal mask and a
      supplementary axillary plexus block. Due to light anaesthesia the patient vomited
      during the course of surgery resulting in a severe pulmonary aspiration
      necessitating four days of mechanical ventilation in the ICU. The safety of the
      laryngeal mask airway for emergency surgery is discussed.

PMID- 9190169
TI  - [Natural atomic radiation and phenomenon of life].

PMID- 9190168
TI  - [Special anesthesiological aspects in patients with Niikawa-Kuroki ("Kabuki Make
      Up") syndrome].
AB  - The Niikawa-Kuroki ("Kabuki Make-up") syndrome (NKS) is a rare disease with a
      characteristic array of multiple congenital anomalies. The syndrome is
      characterised by distinct craniofacial dysmorphias, moderate mental retardation,
      skeletal abnormalities, cardiovascular and urogenital disorders, growth
      retardation and skeletal muscle abnormalities. The inheritance of NKS is not
      completely clear. However, the available data are compatible with an autosomal
      dominant mutation with variable expressivity. There is no specific treatment for
      NKS. The patients require intensive support for the development of their mental
      and physical capabilities. Furthermore, therapy includes operative correction of
      the multiple anomalies. The risk of anaesthesia is increased in these patients
      because of a possible difficult airway, cardiovascular and urogenital diseases,
      and abnormalities of the skeletal muscles. Special problems associated with the
      anaesthetic management in patients with NKS are discussed in this case report.

PMID- 9190170
TI  - [Direction of the vasomotor effects of thrombin is regulated by the vessel
      tonus].

PMID- 9190171
TI  - [Balance of neuromediatory amino acids and impairment of integral brain activity
      caused by local ischemia of frontal lobe in rats: effects of piracetam and
      glycine].

PMID- 9190172
TI  - [Use of phosphatidylcholine liposomes for correction of phospholipid composition
      of mitochondria from medulla oblongata and frontal lobe during hemorrhagic shock
      in cats].

PMID- 9190173
TI  - [Calcium causes decrease in membrane potentials of mitochondria from cultured rat
      cerebellar granular cells during toxic exposure to glutamate].

PMID- 9190174
TI  - [Activity of enzymes of antioxidant protection and level of lipid peroxidation in
      intact NZW mice and mice exposed to mutagens].

PMID- 9190176
TI  - [Asymmetry of electrodermal activity and its dynamics during flight over time
      zones].

PMID- 9190175
TI  - [The loss of sensitivity of the respiratory system to carbon dioxide during
      activation of GABAergic brain structures].

PMID- 9190177
TI  - [The effect of low-intensity laser radiation on functional potential of
      leukocytes].

PMID- 9190178
TI  - [The effect of dithiothreitol on the ultrastructure of cardiomyocytes from the
      pro-oxidant heart region in rats with experimental cardiac insufficiency].

PMID- 9190179
TI  - [Effect of electric skin stimulation on the level of succinate dehydrogenase
      activation and changes in the parameters of glutamatergic synaptic transmission
      in response ro sensory stimulation].

PMID- 9190180
TI  - [DNA repair and O(-)2-generating system of nonspecific defense during induced
      radioresistance].

PMID- 9190181
TI  - [Protective and inhibitory effect of brain extracts on bacterial growth].

PMID- 9190182
TI  - [Mechanisms of histamine-induced raise in calcium levels in cardiomyocytes;
      relative effectiveness of histamine receptors blockers].

PMID- 9190183
TI  - [Effect of synthetic analog of leu-enkephalin on the intensity of DNA synthesis
      in insects].

PMID- 9190184
TI  - [Correction with alpha-tocopherol in combination with nicotinamide and methionine
      of xenobiotics biotransformation during ultrasound-induced liver injury].

PMID- 9190185
TI  - [Biological effect of chorionic gonadotropin and its synthetic peptide fragment
      on cell line HL-60].

PMID- 9190186
TI  - [Reaction to antigenic information after treatment with elevated doses of
      angiogenin].

PMID- 9190187
TI  - [Isolation and partial characteristics of T-cell clones specific for
      mycobacterial antigens in mice with genetically determined differences in
      sensitivity to tuberculosis].

PMID- 9190188
TI  - [Effect of different regimens of gamma-irradiation on formation of cell complexes
      in a population of cultured HeLa cells].

PMID- 9190189
TI  - [Enhancement of antineoplastic activity of sarcolysin by the means of
      transforming it into lipid derivative and incorporating into liposomal membranes
      containing carbohydrate vector].

PMID- 9190190
TI  - [Thermodynamic parameters of binding of murine antitheophylline monoclonal
      antibodies 2G3 with theophylline].

PMID- 9190191
TI  - [Biological effects of synthetic peptide, a fragment of C-terminal region of
      human interferon-2alpha, in a Daudi cell line].

PMID- 9190192
TI  - [Pathogenetic factors of menstrual function disorders in women with pathological
      puberty].

PMID- 9190193
TI  - [Biological and clinical effects of violet and blue light].

PMID- 9190194
TI  - [Effect of diaminodiphenylsulfone on parameters of diurnal rhythm of
      hematological indices in mice].

PMID- 9190195
TI  - [Morpho-functional characteristics of exocrine pancreas during parathyroidectomy
      induced hypocalcemia].

PMID- 9190196
TI  - [Morpho-functional basis for the use of hyaluronic acid in the treatment of acute
      pancreatitis].

PMID- 9190197
TI  - [Interaction of micro-organisms with enterocytes during peroral administration of
      pesticides].

PMID- 9190198
TI  - [The state of biogenic amines in rats with experimental chronic allergic
      encephalitis].

PMID- 9190199
TI  - [Dynamometric equipment for the study of mechanical properties of hollow organs
      of small laboratory animals].

PMID- 9190200
TI  - [Hydrodynamic basis for the choice of cavo-pulmonary anastomosis].

PMID- 9190201
TI  - Keith R. Porter Lecture, 1996. Of mice and men: genetic disorders of the
      cytoskeleton.
AB  - Since the time when I was a postdoctoral fellow under the supervision of Dr.
      Howard Green, then at the Massachusetts Institute of Technology, I have been
      interested in understanding the molecular mechanisms underlying growth,
      differentiation, and development in the mammalian ectoderm. The ectoderm gives
      rise to epidermal keratinocytes and to neurons, which are the only two cell types
      of the body that devote most of their protein-synthesizing machinery to
      developing an elaborate cytoskeletal architecture composed of 10-nm intermediate
      filaments (IFs). Our interest is in understanding the architecture of the
      cytoskeleton in keratinocytes and in neurons, and in elucidating how
      perturbations in this architecture can lead to degenerative diseases of the skin
      and the nervous system. I will concentrate on the intermediate filament network
      of the skin and its associated genetic disorders, since this has been a long
      standing interest of my laboratory at the University of Chicago.

PMID- 9190202
TI  - Sec31 encodes an essential component of the COPII coat required for transport
      vesicle budding from the endoplasmic reticulum.
AB  - The COPII vesicle coat protein promotes the formation of endoplasmic reticulum-
      (ER) derived transport vesicles that carry secretory proteins to the Golgi
      complex in Saccharomyces cerevisiae. This coat protein consists of Sar1p, the
      Sec23p protein complex containing Sec23p and Sec24p, and the Sec13p protein
      complex containing Sec13p and a novel 150-kDa protein, p150. Here, we report the
      cloning and characterization of the p150 gene. p150 is encoded by an essential
      gene. Depletion of this protein in vivo blocks the exit of secretory proteins
      from the ER and causes an elaboration of ER membranes, indicating that p150 is
      encoded by a SEC gene. Additionally, overproduction of the p150 gene product
      compromises the growth of two ER to Golgi sec mutants: sec16-2 and sec23-1. p150
      is encoded by SEC31, a gene isolated in a genetic screen for mutations that
      accumulate unprocessed forms of the secretory protein alpha-factor. The sec31-1
      mutation was mapped by gap repair, and sequence analysis revealed an alanine to
      valine change at position 1239, near the carboxyl terminus. Sec31p is a
      phosphoprotein and treatment of the Sec31p-containing fraction with alkaline
      phosphatase results in a 50-75% inhibition of transport vesicle formation
      activity in an ER membrane budding assay.

PMID- 9190203
TI  - Molecular dissection of a LIM domain.
AB  - LIM domains are novel sequence elements that are found in more than 60 gene
      products, many of which function as key regulators of developmental pathways. The
      LIM domain, characterized by the cysteine-rich consensus CX2CX16-23HX2CX2CX2CX16
      21 CX2-3(C/H/ D), is a specific mental-binding structure that consists of two
      distinct zinc-binding subdomains. We and others have recently demonstrated that
      the LIM domain mediates protein-protein interactions. However, the sequences that
      define the protein-binding specificity of the LIM domain had not yet been
      identified. Because structural studies have revealed that the C-terminal zinc
      binding module of a LIM domain displays a tertiary fold compatible with nucleic
      acid binding, it was of interest to determine whether the specific protein
      binding activity of a LIM domain could be ascribed to one of its two zinc-binding
      subdomains. To address this question, we have analyzed the protein-binding
      capacity of a model LIM peptide, called zLIM1, that is derived from the
      cytoskeletal protein zyxin. These studies demonstrate that the protein-binding
      function of zLIM1 can be mapped to sequences contained within its N-terminal zinc
      binding module. The C-terminal zinc-binding module of zLIM1 may thus remain
      accessible to additional interactive partners. Our results raise the possibility
      that the two structural subdomains of a LIM domain are capable of performing
      distinct biochemical functions.

PMID- 9190204
TI  - Topogenesis of a nucleolar protein: determination of molecular segments directing
      nucleolar association.
AB  - To identify the element(s) in nucleolar proteins which determine nucleolus
      specific topogenesis, we have used different kinds of cDNA constructs encoding
      various chimeric combinations of mutants of the constitutive nucleolar protein
      NO38 (B23): 1) with an amino terminally placed short "myc tag"; 2) with two
      different carboxyl terminally attached large alpha-helical coiled coil
      structures, the lamin A rod domain or the rod domain of vimentin; 3) with the
      sequence-related nucleoplasmic histone-binding protein nucleo-plasmin; and 4)
      with the soluble cytoplasmic protein pyruvate kinase. To avoid the problem of
      formation of complexes with endogenous wild-type (wt) molecules and "piggyback"
      localization, special care was taken to secure that the mutants and chimeras used
      did not oligomerize as is typical of protein NO38 (B23). Using microinjection and
      transfection of cultured cells, we found that the segment comprising the amino
      terminal 123 amino acids (aa) alone was sufficient to effect nucleolar
      accumulation of the construct molecules, including the chimeras with the entire
      rod domains of lamin A and vimentin. However, when the amino-terminal 109 aa were
      deleted, the molecules still associated with the nucleolus. The results of
      further deletion experiments and of domain swaps with nucleoplasmin all point to
      the topogenic importance of two independent molecular regions located at both the
      amino- and carboxyl-terminal end. Our definition of dominant elements determining
      the nucleolar localization of protein NO38 (B23) as well as of diverse
      nonnucleolar proteins will help to identify its local binding partner(s) and
      functions, the construction of probes examining other proteins or sequence
      elements within the nucleolar microenvironment, and the generation of cells with
      an altered nuclear architecture.

PMID- 9190205
TI  - Mitogen-activated protein kinase activation down-regulates a mechanism that
      inactivates cyclin B-cdc2 kinase in G2-arrested oocytes.
AB  - The G2 arrest of oocytes from frogs, clams, and starfish requires that preformed
      cyclin B-cdc2 complexes [prematuration-promoting factor (MPF)] be kept in an
      inactive form that is largely due to inhibitory phosphorylation of this pre-MPF.
      We have investigated the role of mitogen-activated protein (MAP) kinase in the
      activation of this pre-MPF. The cytoplasm of both frog and starfish oocytes
      contains an activity that can rapidly inactivate injected MPF. When the MAP
      kinase of G2-arrested starfish or Xenopus oocytes was prematurely activated by
      microinjection of c-mos or Ste-11 delta N fusion proteins, the rate and extent of
      MPF inactivation was much reduced. Both effects were suppressed by expression of
      the specific MAP kinase phosphatase Pyst 1. These results show that MAP kinase
      down-regulates a mechanism that inactivates cyclin B-cdc2 kinase in Xenopus
      oocytes. In starfish oocytes, however, MAP kinase activation occurs only after
      germinal vesicle breakdown, much after MPF activation. In this case, down
      regulation of the cyclin B-cdc2 inhibiting pathway is a sensitive response to
      hormonal stimulation that does not require MAP kinase activation.

PMID- 9190206
TI  - An essential role of the yeast pheromone-induced Ca2+ signal is to activate
      calcineurin.
AB  - Previous studies showed that, in wild-type (MATa) cells, alpha-factor causes an
      essential rise in cytosolic Ca2+. We show that calcineurin, the Ca2+/calmodulin
      dependent protein phosphatase, is one target of this Ca2+ signal. Calcineurin
      mutants lose viability when incubated with mating pheromone, and overproduction
      of constitutively active (Ca(2+)-independent) calcineurin improves the viability
      of wild-type cells exposed to pheromone in Ca(2+)-deficient medium. Thus, one
      essential consequence of the pheromone-induced rise in cytosolic Ca2+ is
      activation of calcineurin. Although calcineurin inhibits intracellular Ca2+
      sequestration in yeast cells, neither increased extracellular Ca2+ nor defects in
      vacuolar Ca2+ transport bypasses the requirement for calcineurin during the
      pheromone response. These observations suggest that the essential function of
      calcineurin in the pheromone response may be distinct from its modulation of
      intracellular Ca2+ levels. Mutants that do not undergo pheromone-induced cell
      cycle arrest (fus3, far1) show decreased dependence on calcineurin during
      treatment with pheromone. Thus, calcineurin is essential in yeast cells during
      prolonged exposure to pheromone and especially under conditions of pheromone
      induced growth arrest. Ultrastructural examination of pheromone-treated cells
      indicates that vacuolar morphology is abnormal in calcineurin-deficient cells,
      suggesting that calcineurin may be required for maintenance of proper vacuolar
      structure or function during the pheromone response.

PMID- 9190208
TI  - Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by
      site-specific phosphorylation.
AB  - The retinoblastoma protein (pRb) inhibits progression through the cell cycle.
      Although pRb is phosphorylated when G1 cyclin-dependent kinases (Cdks) are
      active, the mechanisms underlying pRb regulation are unknown. In vitro
      phosphorylation by cyclin D1/Cdk4 leads to inactivation of pRb in a
      microinjection-based in vivo cell cycle assay. In contrast, phosphorylation of
      pRb by Cdk2 or Cdk3 in complexes with A- or E-type cyclins is not sufficient to
      inactivate pRb function in this assay, despite extensive phosphorylation and
      conversion to a slowly migrating "hyperphosphorylated form." The differential
      effects of phosphorylation on pRb function coincide with modification of distinct
      sets of sites. Serine 795 is phosphorylated efficiently by Cdk4, even in the
      absence of an intact LXCXE motif in cyclin D, but not by Cdk2 or Cdk3. Mutation
      of serine 795 to alanine prevents pRb inactivation by Cdk4 phosphorylation in the
      microinjection assay. This study identifies a residue whose phosphorylation is
      critical for inactivation of pRb-mediated growth suppression, and it indicates
      that hyperphosphorylation and inactivation of pRb are not necessarily synonymous.

PMID- 9190207
TI  - Down-regulation of G-protein-mediated Ca2+ sensitization in smooth muscle.
AB  - Prolonged treatment with guanosine 5'-[gamma-thio]triphosphate (GTP gamma S; 5-16
      h, 50 microM) of smooth muscle permeabilized with Staphylococcus aureus alpha
      toxin down-regulated (abolished) the acute Ca2+ sensitization of force by GTP
      gamma S, AIF-4, phenylephrine, and endothelin, but not the response to phorbol
      dibutyrate or a phosphatase inhibitor, tautomycin. Down-regulation also abolished
      the GTP gamma S-induced increase in myosin light chain phosphorylation at
      constant [Ca2+] and was associated with extensive translocation of p21rhoA to the
      particulate fraction, prevented its immunoprecipitation, and inhibited its ADP
      ribosylation without affecting the immunodetectable content of G-proteins
      (p21rhoA, p21ras, G alpha q/11, G alpha i3, and G beta) or protein kinase C
      (types alpha, beta 1, beta 2, delta, epsilon, eta, theta, and zeta). We conclude
      that the loss of GTP gamma S- and agonist-induced Ca2+ sensitization through
      prolonged treatment with GTP gamma S is not due to a decrease in the total
      content of either trimeric (G alpha q/11, G alpha i3, and G beta) or monomeric
      (p21rhoA and p21ras) G-protein or protein kinase C but may be related to a
      structural change of p21rhoA and/or to down-regulation of its (yet to be
      identified) effector.

PMID- 9190209
TI  - Expression of an activated rasD gene changes cell fate decisions during
      Dictyostelium development.
AB  - It has been previously demonstrated that the expression of an activated rasD gene
      in wild-type Dictyostelium cells results in formation of aggregates with
      multitips, instead of the normal single tips, and a block in further development.
      In an attempt to better understand the role of activated RasD development, we
      examined cell-type-specific gene expression in a strain stably expressing high
      levels of RasD[G12T]. We found that the expression of prestalk cell-specific
      genes ecmA and tagB was markedly enhanced, whereas the expression of the prespore
      cell-specific gene cotC was reduced to very low levels. When the fate of cells in
      the multitipped aggregate was monitored with an ecmA/lacZ fusion, it appeared
      that most of the cells eventually adopted prestalk gene expression
      characteristics. When mixtures of the [G12T]rasD cells and Ax3 cells were induced
      to differentiate, chimeric pseudoplasmodia were not formed. Thus, although the
      [G12T]rasD transformant had a marked propensity to form prestalk cells, it could
      not supply the prestalk cell population when mixed with wild-type cells. Both
      stalk and spore cell formation occurred in low cell density monolayers of the
      [G12T]rasD strain, suggesting that at least part of the inhibition of stalk and
      spore formation during multicellular development involved inhibitory cell
      interactions within the cell mass. Models for the possible role of rasD in
      development are discussed.

PMID- 9190210
TI  - The nfkb1 promoter is controlled by proteins of the Ets family.
AB  - The gene encoding NFKB1 is autoregulated, responding to NF-kappa B/Rel activation
      through NF-kappa B binding sites in its promoter, which also contains putative
      sites for Ets proteins. One of the Ets sites, which we refer to as EBS4, is
      located next to an NF-kappa B/Rel binding site, kB3, which is absolutely required
      for activity of the promoter in Jurkat T cells in response to activation by
      phorbol 12-myristate 13-acetate (PMA), PMA/ionomycin, or the Tax protein from
      human T cell leukemia virus type I. We show that EBS4 is, required for the full
      response of the nfkb1 promoter to PMA or PMA/ionomycin in Jurkat cells. EBS4 is
      bound by Ets-1, Elf-1, and other species. Overexpression of Ets-1 augments the
      response to PMA/ionomycin and this is reduced by mutation of EBS4. Elf-1 has less
      effect in conjunction with PMA/ionomycin, but by itself activates the promoter 12
      fold. This activation is only partly affected by mutation of EBS4, and a mutant
      promoter that binds Ets-1, but not Elf-1, at the EBS4 site responds to
      PMA/ionomycin as efficiently as the wild-type. Ets proteins may be responsible
      for fine-tuning the activity of the nfkb1 gene in a cell-type-specific manner.

PMID- 9190212
TI  - Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the
      integrin lymphocyte function-associated molecule-1.
AB  - Intracellular signals are required to activate the leukocyte-specific adhesion
      receptor lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) to bind
      its ligand, intracellular adhesion molecule-1 (ICAM-1). In this study, we
      investigated the role of the cytoskeleton in LFA-1 activation and demonstrate
      that filamentous actin (F-actin) can both enhance and inhibit LFA-1-mediated
      adhesion, depending on the distribution of LFA-1 on the cell surface. We observed
      that LFA-1 is already clustered on the cell surface of interleukin
      2/phytohemagglutinin-activated lymphocytes. These cells bind strongly ICAM-1 and
      disruption of the actin cytoskeleton inhibits adhesion. In contrast to
      interleukin-2/phytohemagglutinin-activated peripheral blood lymphocytes, resting
      lymphocytes, which display a homogenous cell surface distribution of LFA-1,
      respond poorly to intracellular signals to bind ICAM-1, unless the actin
      cytoskeleton is disrupted. On resting peripheral blood lymphocytes, uncoupling of
      LFA-1 from the actin cytoskeleton induces clustering of LFA-1 and this, along
      with induction of a high-affinity form of LFA-1, via "inside-out" signaling,
      results in enhanced binding to ICAM-1, which is dependent on intact intermediate
      filaments, microtubules, and metabolic energy. We hypothesize that linkage of LFA
      1 to cytoskeletal elements prevents movement of LFA-1 over the cell surface, thus
      inhibiting clustering and strong ligand binding. Release from these cytoskeletal
      elements allows lateral movement and activation of LFA-1, resulting in ligand
      binding and "outside-in" signaling, that subsequently stimulates actin
      polymerization and stabilizes cell adhesion.

PMID- 9190211
TI  - Bax- and Bak-induced cell death in the fission yeast Schizosaccharomyces pombe.
AB  - The effects of the expression of the human Bcl-2 family proteins Bax, Bak, Bcl-2,
      and Bcl-XL were examined in the fission yeast Schizosaccharomyces pombe and
      compared with Bax-induced cell death in mammalian cells. Expression of the
      proapoptotic proteins Bax and Bak conferred a lethal phenotype in this yeast,
      which was strongly suppressed by coexpression of the anti-apoptotic protein Bcl
      XL. Bcl-2 also partially abrogated Bax-mediated cytotoxicity in S. pombe, whereas
      a mutant of Bcl-2 (Gly145Ala) that fails to heterodimerize with Bax or block
      apoptosis in mammalian cells was inactive. However, other features distinguished
      Bax- and Bak-induced death in S. pombe from animal cell apoptosis. Electron
      microscopic analysis of S. pombe cells dying in response to Bax or Bak expression
      demonstrated massive cytosolic vacuolization and multifocal nuclear chromatin
      condensation, thus distinguishing this form of cell death from the classical
      morphological features of apoptosis seen in animal cells. Unlike Bax-induced
      apoptosis in 293 cells that led to the induction of interleukin-1 beta-converting
      enzyme (ICE)/CED-3-like protease activity, Bax- and Bak-induced cell death in S.
      pombe was accompanied neither by internucleosomal DNA fragmentation nor by
      activation of proteases with specificities similar to the ICE/CED-3 family. In
      addition, the baculovirus protease inhibitor p35, which is a potent inhibitor of
      ICE/CED-3 family proteases and a blocker of apoptosis in animal cells, failed to
      prevent cell death induction by Bax or Bak in fission yeast, whereas p35
      inhibited Bax-induced cell death in mammalian cells. Taken together, these
      findings suggest that Bcl-2 family proteins may retain an evolutionarily
      conserved ability to regulate cell survival and death but also indicate
      differences in the downstream events that are activated by overexpression of Bax
      or Bak in divergent cell types.

PMID- 9190215
TI  - Proceedings of the XIII Seminar on Amebiasis. Mexico City, Mexico, January 29-31,
      1997.

PMID- 9190216
TI  - International Symposium on Radioiodine. Rochester, Minnesota, August 24-27, 1996.
      Proceedings and abstracts.

PMID- 9190213
TI  - Functional interactions between the proline-rich and repeat regions of tau
      enhance microtubule binding and assembly.
AB  - Tau is a neuronal microtubule-associated protein that promotes microtubule
      assembly, stability, and bundling in axons. Two distinct regions of tau are
      important for the tau-microtubule interaction, a relatively well-characterized
      "repeat region" in the carboxyl terminus (containing either three or four
      imperfect 18-amino acid repeats separated by 13- or 14-amino acid long inter
      repeats) and a more centrally located, relatively poorly characterized proline
      rich region. By using amino-terminal truncation analyses of tau, we have
      localized the microtubule binding activity of the proline-rich region to Lys215
      Asn246 and identified a small sequence within this region, 215KKVAVVR221, that
      exerts a strong influence on microtubule binding and assembly in both three- and
      four-repeat tau isoforms. Site-directed mutagenesis experiments indicate that
      these capabilities are derived largely from Lys215/Lys216 and Arg221. In marked
      contrast to synthetic peptides corresponding to the repeat region, peptides
      corresponding to Lys215-Asn246 and Lys215-Thr222 alone possess little or no
      ability to promote microtubule assembly, and the peptide Lys215-Thr222 does not
      effectively suppress in vitro microtubule dynamics. However, combining the
      proline-rich region sequences (Lys215-Asn246) with their adjacent repeat region
      sequences within a single peptide (Lys215-Lys272) enhances microtubule assembly
      by 10-fold, suggesting intramolecular interactions between the proline-rich and
      repeat regions. Structural complexity in this region of tau also is suggested by
      sequential amino-terminal deletions through the proline-rich and repeat regions,
      which reveal an unusual pattern of loss and gain of function. Thus, these data
      lead to a model in which efficient microtubule binding and assembly activities by
      tau require intramolecular interactions between its repeat and proline-rich
      regions. This model, invoking structural complexity for the microtubule-bound
      conformation of tau, is fundamentally different from previous models of tau
      structure and function, which viewed tau as a simple linear array of
      independently acting tubulin-binding sites.

PMID- 9190214
TI  - Evidence for physical and functional interactions among two Saccharomyces
      cerevisiae SH3 domain proteins, an adenylyl cyclase-associated protein and the
      actin cytoskeleton.
AB  - In a variety of organisms, a number of proteins associated with the cortical
      actin cytoskeleton contain SH3 domains, suggesting that these domains may provide
      the physical basis for functional interactions among structural and regulatory
      proteins in the actin cytoskeleton. We present evidence that SH3 domains mediate
      at least two independent functions of the Saccharomyces cerevisiae actin-binding
      protein Abp1p in vivo. Abp1p contains a single SH3 domain that has recently been
      shown to bind in vitro to the adenylyl cyclase-associated protein Srv2p.
      Immunofluorescence analysis of Srv2p subcellular localization in strains carrying
      mutations in either ABP1 or SRV2 reveals that the Abp1p SH3 domain mediates the
      normal association of Srv2p with the cortical actin cytoskeleton. We also show
      that a site in Abp1p itself is specifically bound by the SH3 domain of the actin
      associated protein Rvs167p. Genetic analysis provides evidence that Abp1p and
      Rvs167p have functions that are closely interrelated. Abp1 null mutations, like
      rvs167 mutations, result in defects in sporulation and reduced viability under
      certain suboptimal growth conditions. In addition, mutations in ABP1 and RVS167
      yield similar profiles of genetic "synthetic lethal" interactions when combined
      with mutations in genes encoding other cytoskeletal components. Mutations which
      specifically disrupt the SH3 domain-mediated interaction between Abp1p and Srv2p,
      however, show none of the shared phenotypes of abp1 and rvs167 mutations. We
      conclude that the Abp1p SH3 domain mediates the association of Srv2p with the
      cortical actin cytoskeleton, and that Abp1p performs a distinct function that is
      likely to involve binding by the Rvs167p SH3 domain. Overall, work presented here
      illustrates how SH3 domains can integrate the activities of multiple actin
      cytoskeleton proteins in response to varying environmental conditions.

PMID- 9190217
TI  - [Patterns in the restoration of skin derivatives in warm-blooded animals].
AB  - It is known that the skin derivatives in homeothermic animals appear in the early
      prenatal period of development and do not form during postnatal development.
      However, during skin regeneration, a process of secondary development, it was
      shown experimentally on eight homeothermic animals, in which full-layered
      fragments of skin were removed from different morphofunctional regions of skin,
      that in the skin regenerates its derivatives are formed: hair, sebaceous and
      sweat glands, and skin folds. The data obtained suggest that formation of the
      hair and sebaceous glands requires the presence of special dermal fibroblasts in
      the young connective tissue of regenerants, which are capable of induction of the
      potencies of regenerating epidermis for organogenesis.

PMID- 9190218
TI  - [Electromagnetic information in the phenomenon of life].

PMID- 9190220
TI  - [The Mongolian saiga: its present status and preservation outlook].
AB  - The taxonomic status of the Mongolian saiga has been considered. Data are
      provided about historical findings, and its possible relationship to the
      Pleistocene saiga (Saiga borealis) is reviewed. The current distribution and the
      changes in the Mongolian saiga abundance during recent decades are discussed on
      the basis of published data and the author's field observations. Organization of
      a reserve in Shargin Gobi and additional protected territories beyond its limits
      is substantiated, where some animals from the main preserved population should be
      reintroduced. This will allow preservation of this unique dweller of semideserts
      in western Mongolia during unfavorable conditions, such as epizootics,
      starvation, etc.

PMID- 9190221
TI  - [The concept of medical entomology: the management of the influence of arthropods
      on human health].
AB  - The tasks of medical entomology are analyzed with special reference to the
      development of methods of protection against the harmful influence of arthropods
      on human health and the use of these animals in health sciences. Special
      attention is paid to the following problems: characterization of individual and
      group features of humans and their relationship with arthropods, elucidation of
      the properties of arthropods, determination of the state of their populations,
      estimation of the efficiency of controlling measures, their ecological
      consequences, etc.

PMID- 9190222
TI  - [Carbon dioxide--a universal inhibitor of the generation of active oxygen forms
      by cells (deciphering one enigma of evolution)].
AB  - Studies were carried out on blood phagocytes and alveolar macrophages of 96
      humans, on the cells of the viscera and tissue phagocytes (liver, brain,
      myocardium, lungs, kidneys, stomach, and skeletal muscle), and liver mitochondria
      of 186 random bred white mice. Generation of the active oxygen forms was
      determined using different methods after direct effect of CO2 on the cells and
      biopsies and indirect effect of CO2 on the integral organism. The results
      obtained suggest that CO2 at a tension close to that observed in the blood (37.0
      mm Hg) and high tensions (60 or 146 mm Hg) is a potent inhibitor of generation of
      the active oxygen forms by the cells and mitochondria of the human and tissues.
      The mechanism of CO2 effect appears to be realized, partially, through inhibition
      of the NADPH-oxidase activity. The results are important for deciphering of a
      paradox of evolution, life preservation upon appearance of oxygen in the
      atmosphere and succession of anaerobiosis by aerobiosis, and elucidation of some
      other problems of biology and medicine, as well as analysis of the global
      bioecological problem, such as ever increasing CO2 content in the atmosphere.

PMID- 9190219
TI  - [The effect of antioxidant on the growth and lipid composition of Saccharomyces
      cerevisiae yeasts at different phases of the development of a culture].

PMID- 9190223
TI  - [The cellular aspects of amyloid angiopathies of the iris in open-angle
      glaucoma].
AB  - We studied cellular aspects of amyloid angiopathy of the iris upon decompensation
      of ocular pressure and the role of microcirculatory pathology in pathogenesis of
      the open angle glaucoma. A total of 115 iris biopsies were studied, which were
      taken during antiglaucoma operations and stained by Congo rot and thioflavine for
      amyloid and Toluidine blue for glycosaminoglycans. The biopsies from nine
      patients were studied at the ultrastructural level. Intravasal increase of the
      concentration of preamyloid proteins during spasms of the arterioles and
      capillaries should be considered as a provoking moment of the iris
      amyloidogenesis. Blockade of reticular structures of the microcirculatory basal
      membranes by preamyloid serum proteins, which provides for shedding of amyloid
      fibrils, dystrophic changes and detachment of the endothelial cells from the
      basal membrane, obliteration of lumens of the capillaries and arterioles,
      disturbed integrity of the microvascular barrier and accumulation of preamyloid
      and amyloid proteins in the extracellular matrix, ischemia and focal
      microinfarctions of the iris, and dystrophia of the melanocytes, are subsequent
      key factors. Amyloid angiopathy of the iris is a cause of ischemia of the
      anterior eye part, thus creating conditions for increased intraocular pressure
      and glaucoma.

PMID- 9190225
TI  - [The effect of modified forms of vasopressin on the rat hemostatic system].
AB  - The effect of modified forms of vasopressin (MFV) that do not possess hormonal
      activity on homeostasis in rats was studied. One of the major effects of
      vasopressin (AVP) and its analogs on the blood clotting system, changes in
      fibrinolytic activity (FA) and the activity of plasminogen activator (APA),
      depends on modifications of the amino acid sequence in the peptide molecule. The
      presence of glycinamide in the AVP molecule enhances FA and APA. AVP molecules
      without the glycinamide group exert a more marked influence on procoagulant
      activity in blood.

PMID- 9190224
TI  - [The nature of an anticoagulant isolated from peonies in the central zone of
      Russia].
AB  - The nature of the anticoagulant isolated from the Chinese peony roots has been
      determined. Physicochemical analysis (infrared and mass spectroscopy, and
      polyacrylamide gel electrophoresis) demonstrated the presence of a glycopeptide
      in Paeonia suffraticosae roots. This glycopeptide shares a structural similarity
      with heparin.

PMID- 9190226
TI  - [N. A. Umov's physicomechanical model of living matter (on the 150th anniversary
      of his birth)].
AB  - In 1901, N. A. Umov described his physicomechanical model of living matter and
      later continued to develop it as the most important element of his scientific
      picture of the world. The model contains a definition of life, an indication of
      the source of living matter activity, analysis of the entropy to evolution ratio
      and the role of entropy in the evolution of psychics, and the principles of
      theoretical biology, including the principle of preservation of the amount of
      living matter during evolution. The Universe as a whole is proposed as a
      guarantor of life origin.

PMID- 9190227
TI  - [Pulmonary tuberculosis in youth treated at the Clinic of Lung Diseases and
      Tuberculosis in 1990-1994].
AB  - An analysis of pulmonary tuberculosis morbidity risk factors has been presented
      among patients treated in the Clinic during the period 1990-94. Among the
      morbidity risk factors, apart from the presence of concomitant diseases, the
      deterioration of the standard of living of the population and the low level of
      health education, observed even among people with higher education, was of prime
      importance, followed by a limited number of radiographic, catastral examinations.

PMID- 9190228
TI  - [Difficulties with diagnosis of lung cancer].
AB  - 52 year old patient with pulmonary tuberculosis in the past, was admitted to
      hospital because of massive hemoptysis. The cause of hemoptysis was not find
      during routine examinations. TK of lungs revealed only cirrhosis and
      bronchiectases in upper right lobe. During thoracotomy lung cancer was
      recognised.

PMID- 9190229
TI  - [Tuberculous meningitis--a diagnostic and treatment problem].
AB  - Tuberculous meningitis is one of the most serious form of tuberculosis. The delay
      in diagnosing of tuberculous meningitis results in high mortality. An early
      diagnosis allows to achieve successful effects of treatment.

PMID- 9190230
TI  - [Harmful effects of organic dust on the respiratory system].

PMID- 9190231
TI  - [The role of Lung Diseases and Tuberculosis Clinics of Academic Medicine in
      teaching phthisiology and pneumonology in Lublin].

PMID- 9190232
TI  - [The activity of the Lublin branch of the Polish Society of phthisiopneumonology
      in 1948-1995].

PMID- 9190233
TI  - [Exposure to organic dust and microorganisms as a factor affecting respiratory
      function of workers of purebred horse farms].
AB  - In two farms of purebred horses, microbiological studies of the air and medical
      examination of the workers were performed. The concentration of microorganisms in
      the air were within the range 29.2-336.0 cfu x 10(3)/m3. The respirable fraction
      in most cases was between 30-60% of the total count. The levels of dust and
      endotoxin were low except for one sampling point where the concentration of
      endotoxin was as high as 3.44 g/m3. As many as 16 workers out of the total of 31
      examined reported occurrence of work-related symptoms. However, the results of
      physical examination and of lung function tests were within normal range. A high
      proportion of workers showed a positive skin response to Saccharopolyspora
      rectivirgula (51.6%) and the presence of precipitins to Acinetobacter
      calcoaceticus (32.3%). No significant relationship could be found between the
      presence of symptoms and positive allergological reactions. Total medical results
      indicate the probability of the occurrence of Organic Dust Toxic Syndrome in high
      proportion of the workers.

PMID- 9190234
TI  - [Microflora of the air in sawmills as a potential occupational hazard:
      concentration and composition of microflora and immunologic reactivity of workers
      to microbial aeroallergens].
AB  - Microbiologial studies of the air and allergological examinations of the workers
      were performed in two sawmills processing deciduous wood (mainly oak) and in one
      sawmill processing coniferous wood (mainly pine). The concentration of
      microorganisms in the air was of the order 10(3)-10(4) cfu/m3. The most common
      organisms were corynebacteria (Arthrobacter, Corynebacterium, Brevibacterium,
      Microbacterium), spore-forming bacilli (Bacillus), Gram-negative bacteria
      (rahnella) and filamentous fungi (Aspergillus, Penicillium). The workers
      responded to the extract of pine dust with much higher frequency than to the
      extract of oak dust. The workers processing pine were often sensitized to
      Rahnella while those processing oak were commonly sensitized to Penicillium.
      Precipitin reactions were rare and occurred only with the antigen of Rahnella.

PMID- 9190235
TI  - [The effect of wood dust on the respiratory system. Medical examination of
      furniture factory workers].
AB  - The medical-environmental questionnaire, physical examination and pre-shift and
      post-shift spirometry have been performed in 48 furniture factory workers. The
      workers showed the work-related symptoms: cough, shortness of breath, chest pain,
      headache, general malaise, skin symptoms, eye symptoms, rhinitis. No relationship
      was found between the spirometry values and the frequency of the symptoms. The
      exposed workers showed a significant post-shift reduction of the FVC, FEV1,
      FEV1%VC and PEF (p < 0.001). The higher drops of the spirometric parameters
      occurred in younger workers. The presented data show that processing of wood may
      be associated with the work-related respiratory symptoms and diseases in exposed
      workers.

PMID- 9190236
TI  - [Microflora of the in furniture factors as a potential occupational hazard:
      concentration and composition of microflora and immunologic reactivity of workers
      to microbial aeroallergens].
AB  - Microbiologial studies of the air were performed in two furniture factories. The
      concentration of microorganisms in the air was low, being of the order 10(3)
      cfu/m3. The most common organisms were corynebacteria (Arthrobacter,
      Corynebacterium, Brevibacterium, Microbacterium) and fungi (Aspergillus
      fumigatus, Rhodotorula rubra). Some of the species found in this environment
      possess known allergenic properties. Allergological examinations of the workers
      with environmental aeroallergens have been performed in three departments of one
      factory. The highest frequency of positive skin reactions were observed among the
      workers of the varnishing department which may be due to synergistic effects of
      chemical pollutants. The incidence of precipitin reactions was low among all
      workers.

PMID- 9190237
TI  - [Cytologic and histopathologic examinations of polyps and mucosa in chronic
      allergic and nonallergic rhinitis].
AB  - We evaluated cytograms and tissue sections of nasal polyps and mucosa of 30
      patients with chronic allergic and nonallergic rhinitis. We compared them with
      cytograms and biopsies of 20 asymptomatic persons. We noticed a presence of
      neutrophils in cytograms and in biopsies of patients with allergic rhinitis and
      with nonallergic eosinophilic rhinitis. We observed the metaplasia of endothelium
      in allergic rhinitis, aspirin intolerance and in control group. The obtained data
      create integral view of alterations on the surface and inside of mucosa. Their
      analysis permits for correct classification and treatment of rhinitis.

PMID- 9190238
TI  - [Special issue: Assistant professor of medical studies, Biruta Fafrowicz--head,
      division of pulmonology, Lublin Medical school].

PMID- 9190240
TI  - [Blood platelets as one hemostatic indicator in patients with bronchial asthma].
AB  - Phospholipids forming blood platelets membrane are substrates for oxidative
      phosphorylation in electric and chemical activation of these cells. Beneficial
      effect of corticosteroids on the course of asthma is connected with inhibition of
      phospholipase A2. This enzyme is responsible for the generation of allergic
      reaction membrane mediators like leukotrienes, prostaglandins and other
      lipoxygenase products. Three groups of asthmatic patients were observed: I group-
      patients with mild asthma, II group--patients with moderate asthma, III group-
      patients with severe, corticosteroid-dependent bronchial asthma. Changes of
      platelets membrane phospholipids structure in these groups of asthmatic patients
      were analyzed. There were significant differences in membrane phospholipids
      structure between II and III group of patients and control subjects (p < 0.01).

PMID- 9190239
TI  - [Phenotype of lymphocytes in bronchoalveolar lavage and peripheral blood with
      different clinical presentations of sarcoidosis].
AB  - The aim of this study was to investigate the relationship between the
      bronchoalveolar cell counts, the phenotypic characteristics of bronchoalveolar
      lavage and peripheral lymphocytes and the clinical manifestation of sarcoidosis.
      24 patients with sarcoidosis of the lung were examined. Patients were divided
      into groups based on the presence and the type of clinical symptoms (patients
      with symptoms of Lofgren syndrome, with constitutional and respiratory symptoms
      and symptomless patients). The lymphocyte subtypes were analysed using the panel
      of monoclonal antibodies Simultest IMK Plus with the flow cytometry (Orto Cytoron
      Absolute). The highest ratio CD4/CD8 in BALF was found in patients with symptoms
      of Lofgren Syndrome (mean 11.4), the lowest in symptomless patients (mean 4.5).
      The bronchoalveolar cell count and the percentages of phenotypes of peripheral
      blood lymphocytes did not differ significantly between the groups of patients.
      The bronchoalveolar lavage performed in patients with sarcoidosis indicates
      various intensity of alveolitis dependent on the clinical manifestation.

PMID- 9190241
TI  - [The influence of selected antibiotics on the central action of aminophyllines-
      experimental studies].
AB  - Methylxanthines and some antibiotics can cause side effects, provoked by their
      central action, e.g. seizures. The epileptogenic effects of given drugs can be
      intensified during combined treatment, as a result of pharmacological
      interactions. In the present study the author investigated the influence of some
      commonly used antibiotics: benzylpenicillin, cefuroxime, doxycycline and amikacin
      upon central activity of methylxanthines in mice. The obtained results suggest,
      that all tested antibiotics, mainly benzylpenicillin, enhanced epileptogenicity
      of aminophylline in chemical seizures test. benzylpenicillin as only one among
      chosen antibiotics presented her own convulsant activity. During
      electrostimulation test, benzylpenicillin, doxycycline and amikacin intensified
      convulsions induced by methylxanthines. Only cefuroxime had no influence upon
      central action of methylxanthines in that experiments. Analysis of drugs' plasma
      levels, with using immunofluorescence methods, excluded pharmacokinetic
      interactions between them. Results of present investigation indicate, that there
      is a possibility of intensification of drugs' convulsant activity during combined
      treatment-aminophylline with some antibiotics in medical practice.

PMID- 9190242
TI  - [Effect of beta 2-adrenergic agonists on neurotoxic action of aminophyllines].
AB  - The purpose of the present investigation was to evaluate whether the beta 2
      adrenergic agonists affect the pharmacodynamics and pharmacokinetics of
      aminophylline-induced seizures. Adult male Albino Swiss mice were treated i.p.
      with salbutamol, fenoterol or terbutaline and 30 min. later they received
      i.p.aminophylline. During 90 min. observation clonic and tonic seizures and also
      mortality of mice were registered. Moreover the influence of beta 2
      adrenomimetics on electroshock-induced seizure threshold (CS 50) and on plasma
      aminophylline concentration was estimated. It was found that pretreatment with
      salbutamol, fenoterol and terbutaline decreased the ED 50 (for clonic and tonic
      seizures) and LD 50 of aminophylline. Fenoterol decreased but terbutaline
      increased the CS 50 in mice. Only terbutaline elevated significantly the plasma
      concentration of aminophylline. The data indicate that concomitant treatment with
      beta 2-adrenergic agonists together with aminophylline increase the risk of
      aminophylline-induced seizures. Thus plasma monitoring of aminophylline
      concentration could be used in all patients treated simultaneously with beta-2
      adrenergic agonists and aminophylline.

PMID- 9190244
TI  - [Bacterial endotoxins produced by Alcaligenes faecalis and Erwinia herbicola as
      potential occupational hazards for agricultural workers].
AB  - Laboratory animals (guinea pigs and rabbits) were exposed to the inhalation of
      aerosolized endotoxins derived from the cell mass of Alcaligenes faecalis and
      Erwinia herbicola, the Gram-negative bacteria commonly occurring in organic
      dusts. Single 1 hour-lasting exposure caused the significant increase in the
      number of free lung cell, mostly lymphocytes, compared to the control group
      exposed to saline (P < 0.001). Prolonged exposure to tested endotoxins (Fifteen 1
      hour-lasting exposures every second day) caused both specific and non specific
      immunological changes: enhanced inhibition of leukocyte migration production of
      precipitins, and activation of alveolar macrophages, wes assessed by greater
      antibacterial activity and increased interleukin I (IL-I) production. The results
      indicate that the endotoxins of examined bacteria represent a potential risk of
      inflammatory lung reaction and respiratory disease for agricultural workers
      inhaling organic dusts contaminated with these organisms.

PMID- 9190243
TI  - [The influence of organic dust on the chemotaxis of lung cells. Experimental
      studies].
AB  - Mechanisms of chemotaxis of alveolar macrophages (AMs) and neutrophils (PMNs) in
      response to microbial products derived from organic dust were studied using
      blindwell chemotaxis chamber technique. Seven different agents (extract and
      endotoxin of Erwinia herbicola, extracts from Thermoactinomyces vulgaris and
      Aspergillus fumigatus, thermophilic protease and two preparations of glucans),
      were used for experiments. These agents were evaluated for their ability to
      direct attraction of AMs and PMNs and stimulation of alveolar macrophages to
      release chemotactic factors for other AMs and PMNs. The microbial products were
      able to attract both AMs and PMNs directly in a dose-dependent manner and the
      exposure of cultured AMs to most agents were stimulatory for production of
      chemotactic activity for AMs and PMNs. The generation and release of this
      activity by AMs may provide a mechanisms for the initiation and amplification of
      inflammatory reactions in the lung after inhalation of organic dust. Results of
      these in vitro studies may be relevant to the pathogenesis of alveolitis in
      organic dust-induced lung diseases.

PMID- 9190245
TI  - [Clinical evaluation of efficacy and tolerance of oral treatment with ambroxol in
      patients with chronic bronchitis].
AB  - This study was designed to examine the efficacy and tolerability of ambroxol
      (Ambrosol) on the symptomatology of chronic bronchitis among in- and out
      patients. Seventy patients were included in the trial and divided into two random
      groups. The patients were treated in a double-blind way with either Ambrosol or a
      placebo for 2 months. The physician and the patient assessed the following
      points: the feeling general well-being, the symptoms of a cold and of fever, the
      need for treatment with antibiotics, the amount, viscosity and colour of sputurn,
      the difficulty in expectoration, the severity of coughing and any changes in
      breathlessness while at rest. In order to carry out these subjective assessments
      we used a scoring system. We observed that, breathlessness while at rest and the
      rate of exacerbation was significantly lower in the Ambrosol group after 2 weeks
      of therapy. Sputum viscosity, difficulty in expectoration and severity of
      coughing were reduced in this group after 4 or 8 weeks. Throughout the 2-month
      period of therapy, the tolerability of ambroxol was good. A total of 4 patients
      reported side-effects of various degrees of severity. One patient stopped the
      therapy due to these side-effects (dizziness). There was no significant
      difference in the number of side-effects between the two groups (Ambrosol vs
      Placebo).

PMID- 9190246
TI  - [The effect of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on
      results of spirometric measurements].
AB  - The effect of fiberoptic bronchoscopy and bronchoalveolar lavage on the
      functioning of the respiratory system was studied in 72 patients (42 males and 30
      females). The bronchoscopy was performed in the sitting position. Supplemental
      oxygen was not given to all the evaluated patients. The group included 24
      patients with lung cancer, 9 with sarcoidosis, 12 with tuberculosis, 1 with
      farmer's lung and 10 with other lung diseases (pneumonia, COPD). A control group
      consisted of 16 patients who were undergoing routine diagnostic endoscopy but who
      were seen to be without lung disease. Group BF (39 individuals) received only a
      bronchoscopic examination, group BF+BAL (33 persons) received a bronchoscopy
      followed by BAL using 140 ml. of normal saline solution as a lavage fluid. After
      the bronchoscopic examination there were significant differences in all
      spirometric measurements, except MEF25. The bronchoscopy and bronchoalveolar
      lavage caused a transient fall in FEV1, VC, MEF50, MEF75 (7.7-9.4%) which was
      similar in both groups. These measurements returned to normal after 24 hours. The
      testing of pulmonary functioning before the bronchoscopy was seen to be
      clinically important for safety of the patient undergoing this procedure.

PMID- 9190248
TI  - [Effects of microgravity on indices of hemodynamics in monkeys during postural
      tests].
AB  - Effects of the 6-day flight on board Cosmos 1667 on the dynamics of arterial
      pressure (AP) and the linear velocity of blood flow in the common carotid artery
      were studied with modified postural tests in the experiment with Macaca mulatta
      No. 18933. Initially, the postural test procedure and the method of mitigating
      the psychoemotional stress due to transition of the tilt-table were tried out on
      21 primates. Administration of the functional test in microgravity was found to
      exert both qualitative and quantitative effects. The last mentioned were
      registered only in the primates tilted downward and included lowered AP vs.
      elevated AP in the control, and absence of typical bradycardia.

PMID- 9190247
TI  - Effects of haloperidol and cocaine pretreatments on brain distribution and
      kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application
      of PET to drug pharmacokinetic study.
AB  - Repeated administration of methamphetamine (MAP) causes behavioral sensitization
      in animals. We previously reported that the maximum accumulation level of
      [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the
      control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist)
      prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake
      blocker) has the cross-behavioral sensitization with MAP. In the present study,
      to elucidate the relation between the MAP-induced behavioral sensitization and
      the pharmacokinetics of MAP, we investigated the effects of haloperidol and
      cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP
      using positron emission tomography (PET). A significant increase of [11C]MAP
      uptake into the sensitized dog brain was prevented by haloperidol and cocaine
      pretreatments. These pharmacokinetic changes were not due to the changes in the
      rate of MAP metabolism. These results suggest haloperidol and cocaine can change
      the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The
      variations of MAP-accumulation may affect the development or expression of MAP
      induced behavioral sensitization.

PMID- 9190249
TI  - [Effects of the tone of arterial vessels on the antiorthostatic response of
      hemodynamics].
AB  - Contribution of the original angiotensin-2 controlled arterial tone to the shifts
      in systolic and diastolic arterial pressure (AP) was assessed in unconscious rats
      during tail-suspension. With this technique, values of original mean AP were
      elevated from 80-110 to 111-140 mm Hg. In the head-down position, rise in the
      tone was concurrent to a twofold increase in the number of "uncompensated"
      responses and a similar decrease in the number of test-resistant responses. The
      original arterial tone high, maximum decline of diastolic pressure was
      significantly less pronounced. Recovery of both systolic and diastolic arterial
      pressures was more dynamic against the background of high original tone.
      Magnitude of the diastolic AP variation dominated over that of systolic AP. These
      results are being analyzed in comparison with the data about orthostatic
      compensatory reactions.

PMID- 9190250
TI  - [Prophylactic use of prostatilen in rats prior to exposure to +Gz loads as a way
      of reducing changes in urogenital organs].
AB  - Experimental verification of prostatilen prophylactics of changes in the
      urogenital organs consequent to g-loads was the idea of the work. The experiment
      was performed with 37 mongrel white male rats weighing 200-250 g who were exposed
      to the head-pelvis g-loads (+Gl) at 10 units. Behavior reactions of the rats were
      assessed with the "open field" technique immediately after centrifugation;
      weighing coefficients of the urogenital organs (the organ/body mass relation)
      were determined, and histological and morphometric analyses of prostate, testis
      and kidney were made. A significant moderating effect of prophylactic prostatilen
      on the stress-reactions in animals was first revealed; prostatilen was also found
      to speed up adaptation. This was concluded from normalization of the
      hemodynamics, a decrease in venous plethora and epithelial dystrophy, absence of
      basophilia in conjunctive tissue of the urogenital organs. Distention and
      overfilling of acini by secret and the number of epithelial acinus hulled into
      the lumen were markedly less in prostate. Spermatogenesis in testis was
      normalized, too. The histological profile of kidney approached the norm. Results
      of the experiment showed that prostatilen is a promising preparation from the
      standpoint of moderation of stress-reactions and counteraction of disorders in
      the urogenital organs caused by g-loads.

PMID- 9190251
TI  - [Impairment of antiviral cellular resistance and possibilities of its correction
      during acute altitude hypoxia].
AB  - Antiviral cell resistance of blood monocytes and lymphocytes was studied in 29
      healthy human subjects subjected to acute altitude hypoxia (AAH) in climatic
      chamber TABAI, and 39 healthy males during rapid ascent from the sea level up to
      3250 m. The antiviral resistance of immune cells was found to be suppressed by
      AAH. Double blind method was used to compare effects of placebo, dexamethasone
      and olifen (approved by the Pharmacology Committee of the Russian Ministry of
      Health as an antihypoxic preparation) on the antiviral resistance of cells during
      AAH. Unlike dexamethasone, from the onset of AAH olifen prevented decline of the
      antiviral resistance of cells; olifen successfully remedied disorders resulted
      from stay in AAH.

PMID- 9190252
TI  - [Effects of a hypoxic stimulus on the dependence of tissue respiration on oxygen
      pressure in vitro].
AB  - Experimental studies of the dynamics of energy exchange in tissues of the rats'
      visceral organs (brain, heart, liver, and kidney) shortly after hypoxic
      stimulation displayed substantial variations in the respiratory activity of
      visceral tissues, and Km for oxygen at the start of the follow-on reaction (24 h,
      72 h, and 120 h) which subsided later on (240 h and 360 h). These were in concert
      with a gross decline in the intensity of visceral tissue breathing at the initial
      oxygen pressure in vitro and a rise at critical pO2, a decrease in the affinity
      of cardiac, hepatic and renal tissues for oxygen at the onset of the follow-on
      reaction and an increase in the affinity at subsequent time points. Throughout
      the period of observation, high affinity for oxygen was observed in cerebral
      tissues. Combination of alpha-tocopherol and the hypoxic stimulus substantially
      suppressed the respiratory activity in all the visceral tissues of rats at the
      initial oxygen pressure and in the liver and kidney, at critical pO2. Increased
      utilization of the low pressure oxygen was observed in the brain and the heart.
      More pronounced changes in tissue affinity for oxygen were revealed in the heart
      and the liver, and least pronounced, in the brain and the kidney. A conclusion is
      drawn that alpha-tocopherol can strongly influence moderation of the stressful
      factor on the level of tissue homogenates.

PMID- 9190253
TI  - [Combined effects of various forms of motor deprivation and gamma irradiation on
      the higher nervous activity in rats].
AB  - Effects of gamma-radiation at a dose of 3 Gy against either antiorthostatic
      hypodynamia (AOH) or hypokinesia (HK) on formation of the differentiated motor
      drinking reflex (DR) were compared. Each of the forms of motor deprivation
      hindered the elaboration of DR; gamma-irradiation aggravated these disorders. At
      the same time, AOH led to significantly more severe disturbances in the higher
      nervous activity including the generalized excitation, pathologic aggressiveness
      and neurotization of animals. In contrast, hypokinesia stimulated the active
      elements of behavior which inhibit the passive-defensive behavior and a fear
      reaction. Therefore, the modifying effect of irradiation becomes apparent only if
      combined with AOH.

PMID- 9190254
TI  - [Improvement of protective and survival means as a current ecological-ergonomic
      problem in aviation].
AB  - Science and application aspects of the ergonomic enhancement of protective and
      survival means for aviation personnel under the present-day operational
      environment have been studied. Substantiated and presented is a concept of
      ergonomic enhancement of these means and possibly marked improvement of
      professional readiness, and maintenance of work capacity and occupational health
      of aviation personnel affected by a combination of adverse factors by way of a
      more thorough consideration of human operator's characteristics in the process of
      design and evaluation of protective means. Methods proposed for evaluation of
      environmental effects on and assessment of the ergonomic stimulation of the
      quality and intensity of flying activity have been analyzed.

PMID- 9190255
TI  - [Mast cells as a test of body state during electromagnetic exposure of varying
      intensity].
AB  - Effects of single and repeated exposure of mice, rats, and rabbits in magnetic
      fields at 50 Hz and 2 kA/m, 16 kA/m, and 32 kA/m on the populations of dermal,
      intestinal, and popliteal lymph node labrocytes were studied immediately and
      within one month after exposure. Single exposure in the magnetic fields of 2 kA/m
      and 16 kA/m for 4 hours did not produce any changes in labrocytes of these
      organs. Repeated exposure to 2 kA/m, 16 kA/m, and 32 kA/m for 4 hours during 5
      days modulated the functional activity of labrocytes in all the organs. More
      extended (1.5-2 months) repeated exposure to the intensive magnetic field (32
      kA/m) stimulated adaptation and regain of labrocyte populations in the dermal and
      popliteal lymph nodes whereas enhanced secretion, i.e. degranulation of
      labrocytes persisted in the intestine. Following one month after the 1.5-2-month
      exposure to 32 kA/m, labrocyte populations were recovered with the maximum effect
      in the lymph nodes. High magnetic sensitivity of labrocytes revealed in this
      study can be used as a test of body reactivity and adaptation to this physical
      agent. Differences in the reactivity of labrocytes of individual organs and
      species must be taken into account.

PMID- 9190256
TI  - [Use of fast-acting adaptogens and symptomatic means during evacuation of trauma
      victims by air transportation].

PMID- 9190257
TI  - [Development of aviation medicine in Germany].

PMID- 9190258
TI  - [Bion-11 project: preliminary results and outlook for the future].

PMID- 9190259
TI  - [The Second Symposium: Science-NASA].

PMID- 9190260
TI  - Synaptic Plasticity and Cellular Mechanisms of Memory. Aussois, France, June 3-7,
      1996. Proceedings and abstracts.

PMID- 9190261
TI  - Ultrastructure of infection, development and gametocyst formation of
      Ascogregarina taiwanensis (Apicomplexa: Lecudinidae) in its mosquito host, Aedes
      albopictus (Diptera: Culicidae).
AB  - The life history of the protozoan parasite Ascogregarina taiwanensis in mosquito
      larvae (Aedes albopictus, collected in southern Taiwan) was shown to consist of
      two consecutive stages--intracellular and extracellular. Light microscopy showed
      that most trophozoites moved into the Malpighian tubules and developed into giant
      trophozoites during the first day pupa. The locomotion may be associated with
      bristle-like ridges of the trophozoite. The stage for sexual reproduction, i.e.,
      the gamete, was then formed by segmentation of the giant trophozoite and twisting
      off the anucleate extremities of the body. Sexual reproduction occurred via
      fertilization by fusion of two resulting gametes, presumably two opposed sexes.
      The fused gametes finally generate the formation of the gametocyst, within which
      oocysts develop by budding from the cytoplasmic mass. This type of sexual
      reproduction has not been reported previously in any gregarine protozoa. We here
      proposed it as a new hypothesis for further elucidation of the protozoan
      reproduction.

PMID- 9190262
TI  - Germination of Nosema algerae (Microspora) spores: conditional inhibition by D2O,
      ethanol and Hg2+ suggests dependence of water influxupon membrane hydration and
      specific transmembrane pathways.
AB  - The germination of microsporidian spores under conditions expected to affect
      water flow across the plasma membrane-wall complex was studied by assessing their
      responses to in vitro stimulation with Na+ or K+. Partial or full substitution of
      common water with D2O, which more effectively coats ions and electrostatically
      charged cell surfaces with relatively stable hydration layers, delayed and
      inhibited spore germination in a concentration-dependent manner; yet,
      preincubation in 100% D2O did not change the normal response to standard
      stimulation. Water structure-breaking conditions, such as an increase in
      temperature (within the 15 degrees C to 40 degrees C range) or in ionic strength
      (1- to 10-fold normal), opposed the inhibition by D2O and allowed significant
      stimulation by Li+, the monovalent cation with the largest hydration diameter and
      a usually weak stimulant action on the spores. Ethanol, known to reduce water
      permeation across cell membranes and phospholipid bilayers, also caused a
      powerful and dose-dependent (1% to 4% v/v) inhibition of spore germination, but
      pretreatment with ethanol did not affect the normal response. HgCl2, an inhibitor
      of specific water channels, blocked spore germination at just 250 microM in the
      normal stimulation solution irrespective of the temperature, and permitted only a
      delayed response in high salt stimulation solutions. However,the inhibition by
      Hg2+ was abolished by the simultaneous presence of 2-mercaptoethanol in the
      medium. These results suggest (1) that spore germination is keenly dependent upon
      the hydration states of both the plasma membrane-wall complex and the stimulant
      ions, and (2) that osmotic water flows into the spores through specific
      transmembrane pathways with critical sulfhydryl groups, i.e., analogous to the
      water channels that facilitate water movements across the plasma membranes of
      highly permeable cells.

PMID- 9190263
TI  - An NADP-glutamate dehydrogenase from the green alga Bryopsis maxima. Purification
      and properties.
AB  - NADP-glutamate dehydrogenase (EC 1.4.1.4:NADP-GDH) was purified to
      electrophoretic homogeneity from the multinuclear-unicellular green marine alga
      in Siphomales, Bryopsis maxima, and its properties were examined. M(r) of the
      undenatured enzyme was 280 kDa, and the enzyme is thought to be a hexamer of 46
      kDa subunit protein. Optimum pHs for the reductive amination and oxidative
      deamination were 7.5 and 8.2-9.0 respectively. The enzyme displayed NADPH/NADH
      specific activities with a ratio of 18:1. Apparent K(m) values for 2
      oxoglutarate, ammonia, NADPH, glutamate and NADP+ were 3.0, 2.2, 0.03, 3.2 and
      0.01 mM respectively. The enzymochemical characteristics of the GDH were studied
      and compared to those of other species. The B. maxima GDH was insensitive to 5 mM
      Ca(2+) and to 1 mM EDTA in contrast to higher plant NAD-GDHs. Chemical
      modifications with DTNB and pCMBS suggested that cysteine residues are essential
      for the enzymatic activity as in other species GDHs. The GDH was not affected by
      1 mM purine nucleotides, suggesting that the enzyme is not allosteric, in
      contrast to animal NAD(P)-GDHs and fungal NAD-GDHs.

PMID- 9190264
TI  - [Ecology-related health problems in the Far North].

PMID- 9190265
TI  - [Characteristics of respiratory and cardiovascular systems of workers with
      extended length of service at asbestos plants].
AB  - Examination of 72 individuals (including 62 workers of asbestos production and 10
      silicosis patients) revealed that asbestos dust primarily causes hypoxemia
      followed by pulmonary ventilation disorders and characteristic X-ray signs of
      asbestosis. Hypoxemia is associated by reliable changes in functioning of left
      ventricle and central hemodynamics. Degree of hypoxemia appeared to correlate
      with echocardiographic signs of malfunction of left ventricle and chronic heart
      failure.

PMID- 9190266
TI  - [Changes in the state of monooxygenase system and lipid peroxidation under the
      effects of carcinogenic dust].
AB  - The work was aimed to study relationship of monooxygenase system and lipid
      peroxidation in experiments and in clinical group. The examinees were workers
      engaged into graphite ware production and exposed to low fibrogenic dust of coke
      and graphite with carcinogens (including 3,4-benzpyrene). The experimental data
      and examination materials prove the carcinogens to alter seriously those systems.
      Long stimulation of monooxygenase system and activation of lipid peroxidation
      could result in more intensive carcinogenic effects of polycyclic aromatic
      hydrocarbons being a component of coal pitch.

PMID- 9190267
TI  - [Morphogenesis of occupational fluoride osteopathy].
AB  - Fluor osteopathy, as the authors suppose, is a morphologic repetition of
      phylogenesis early stages in osteogenesis. Thus, osteosclerosis and osteoporosis
      demonstrated by X-ray should be considered as manifestation of bone fluorosis.
      Fluor-induced changes of bone tissue could not be adequately termed as
      "osteoporosis" and "osteosclerosis", so is defined as "fluor osteopathy".

PMID- 9190268
TI  - [State of the nervous system in workers engaged in the production of plastic
      materials: data of screening and electrophysiologic studies].
AB  - Moderate levels of dioctyl phthalate, hydrogen chloride and carbon monoxide are
      features of ambient air in production of linoleum, polyvinylchloride decorative
      filv and in other modern plastic materials production shops. The workers were
      diagnosed as having latent signs of neurotoxicity--vegetative dysfunction with
      prevalent parasympathetic tone and inactive polyneuropathy shown by
      electroneuromyography (higher thresholds of pain sensation and muscular
      excitability, altered morphology of motor response, trend to longer final
      latency.

PMID- 9190269
TI  - [Evaluation intensity and hardness of work in conditions of high altitude
      migration].

PMID- 9190270
TI  - [Mobile mining machines as example of autonomic complex automatization in
      industrial medicine].

PMID- 9190271
TI  - [Epidemiologic study of mortality of workers of metallurgy enterprise in Nizhni
      Tagil].
AB  - The article studies long-term effects of occupational factors on metallurgists'
      health. The epidemiologic research revealed that hard physical work in chronic
      and intensive heating microclimate with high levels of dust increases the
      mortality risk among workers engaged into open-hearth, necking, converter and
      blast furnace shops (the death causes--arterial hypertension, coronary heart
      disease, pneumonia, bronchitis, tracheal and bronchial cancer, lung and
      pancreatic carcinoma). The auxiliary workers of those shops, who face
      intermittent influence of the same factors demonstrated the mortality levels
      insignificantly different from those of a reference region. Influence of
      chemicals containing carcinogens increases the mortality among workers or non
      coke and coke shops (the death causes--tracheal, bronchial and lung cancer.

PMID- 9190272
TI  - [Hearing function of workers of "noisy" occupations at the Podolsk machinery
      plant and effectiveness of therapeutic measures].
AB  - In recent years noise and vibration have become dominant hazards influencing
      workers' health. A significant share of the resulting disease in covered by
      occupational deafness. The article demonstrates data of hearing examination among
      262 workers exposed to intermittent noise of 95-100 dB A. Slow progress of
      occupational deafness and bilateral cochlear neuritis with over 15 years of
      service appeared to be characteristic for the examinees. Helium neon laser
      applied on mastoid process and general improving treatment appeared to be
      effective.

PMID- 9190273
TI  - [Hygienic characteristics of work conditions at large Hydroelectric Power Plants
      with mechanization and automatization].
AB  - The article touches upon hygienic problems associated with mechanization and
      automation of major hydroelectric power stations. The authors present criteria to
      evaluate work conditions of the main occupations participating in the technologic
      process of hydroelectric power stations.

PMID- 9190274
TI  - [Prevention of ophthalmic coniosis in workers of railway car construction plant
      in Kralyovo].

PMID- 9190275
TI  - [Hygienic evaluation of an enameled bathtub and washer plant].

PMID- 9190276
TI  - [Use of pattern recognition methods in solving tasks of ecological epidemiology].

PMID- 9190277
TI  - Comments on Mayes and Downes: "What do theories of the functional deficit(s)
      underlying amnesia have to explain?".

PMID- 9190278
TI  - [Low loosening rate of a cemented titanium straight shaft prosthesis in long-term
      follow-up].
AB  - Aseptic loosening is still a major problem in total hip replacement. We studied
      the mid-term results of a straight stem femoral prosthesis made from titanium
      alloy (BiContact) and implanted with the use of bone cement. 250 hips in 238
      patients have been implanted between 8/87 and 12/88 and followed up. 172 patients
      were alive and could be reached after 7 years. Two patients had to undergo
      revision surgery within the follow up period, and in two other patients
      radiolucencies could be found. A loosening rate of 1.2% and a rate of
      radiolucencies of another 1.2% indicate that the combination of a titanium alloy
      stem prosthesis with bone cement not necessarily leads to early loosening or a
      high loosening rate, which has been supposed by several authors. The design of
      the individual prosthesis seems to be of greater importance than the materials
      used.

PMID- 9190279
TI  - [Fixation of femoral shaft fractures from a Swiss viewpoint. An international
      prospective controlled study by the Study Group for Osteosynthesis Problems].
AB  - A prospective, controlled study of fixation for femoral shaft fractures was
      undertaken by the Documentation Centre of the Association for the Study of
      Internal Fixation (AO/ASIF) at 7 Swiss and 5 foreign clinics in Europe, South
      America and Asia. 283 fractures in 272 patients were evaluated. 17% of all
      patients suffered a polytrauma. Only two fractures (1%) were treated
      conservatively. Ten percent of all fractures were stabilised by external
      fixation, 35% were plated and 54% were treated by reamed intramedullary nailing.
      An ARDS and deep venous thrombosis occurred in 1% respectively. The local
      infection rate was 2%. Seven patients (2.5%) died perioperatively. 32 fractures
      (12%) were reoperated. At follow-up 86% of all fractures appeared consolidated on
      radiography. Full limb function was restored in 61% of all patients, slight
      impairment persisted in 32% and 6% of all patients remained severely handicapped.
      The average age of the female patients was significantly higher in Europe. Wide
      differences existed in the administration of prophylactic antibiotics and
      antithrombotic drugs. In some centers antithrombotic drugs were not part of the
      treatment scheme. Femoral shaft fractures were treated with high priority in
      Switzerland. Patients profited from short transport ways and from the routine use
      of high end material. Most operations in Switzerland were performed by
      registrars. Their assessment of stability of the fixation was high, as 90% of all
      patients were allowed to bear weight postoperatively. There is an international
      consensus on the need for surgical stabilisation of femoral shaft fractures.
      However divergent views on surgical management and perioperative care remain.

PMID- 9190280
TI  - [The UFN-system (unreamed femoral nail)--avoidable intra- and postoperative
      complications].
AB  - We give an account of the first Austrian clinical results of a prospective study
      dealing with fractures of the femoral shaft treated with the UFN-system, the
      intraoperative handling especially considering the intra- and postoperative
      complications. The UFN-system combines the advantages of numerous proximal
      interlocking options for the treatment of nearly all femoral fracture patterns
      with that of the unreamed nailing (biological osteosynthesis, primary stability
      with individual after-treatment, high patient's comfort and early mobilisation).
      Within two years (VII/94-VII/96) sixty closed and four second degree open
      fractures were stabilized with the unreamed femoral nail. In twelve cases we used
      the spiral blade interlocking technique. Five times we changed from external
      fixator to the UFN. The fractures were classified according to the AO
      classification. In 64 implanted UFN there occurred twelve intraoperative and four
      postoperative complications. In five cases reoperation was necessary. Failings in
      the operative technique, numerous different experienced surgeons and a deficient
      after_treatment led to our pitfalls.

PMID- 9190281
TI  - [Vienna Shoulder Score (VSS) and Vienna Shoulder Formula (VSF) for follow-up and
      assessment of shoulder and shoulder girdle injuries].
AB  - The Vienna Shoulder Score (VSS) was screened by two groups of patients for use in
      medical expertises and follow-up examinations. One group (n = 157) consisted of
      patients with healed clavicular bone fractures, the other group (n = 130)
      consisted of healthy individuals. The study proved that the VSS is a useful,
      exact and fast method of shoulder evaluation after injuries to the shoulder and
      shoulder girdle. The side dominance is of no influence to the outcome of the VSS.
      The Vienna Shoulder Formula (VSF) helps to equalize the age factor in shoulder
      examinations.

PMID- 9190282
TI  - [The treatment of therapy-resistant lateral epicondylitis].
AB  - Failed treatment for chronic or refractory lateral epicondylitis can successfully
      be avoided strictly respecting guidelines in diagnosis, treatment and patient
      selection. Co-existing or simply other pathologic conditions as radial nerve
      compression neuropathy or instability of the elbow are evident reasons for
      failure and have to be treated accordingly to the condition. Inadequate patient
      selection, lack of compliance in performing therapy as well as ongoing cumulative
      trauma exposure are further factors compromising correct treatment and have to be
      ruled out prior to surgical therapy.

PMID- 9190283
TI  - [Early functional treatment of a 5th metatarsal fracture using an orthopedic
      boot].
AB  - The fracture of the base of the fifth metatarsal bone is a common fracture of the
      foot. We differentiate avulsion fractures of the apophysis from meta-diaphysial
      of the Jones-Type. In the literature you find many different methods of treatment
      extending from simple immobilization through functional strapping to
      osteosynthesis of the fracture. Depending on the method of treatment the results
      are quite different especially in the period of immobilization and the period of
      sick-leave. From March 1988 to September 1991 52 patients of the orthopedic
      clinic Kantonsspital Liestal/Switzerland with a fracture of the base of their
      fifth metatarsal bone were treated functionally with a special orthopedic shoe
      and were studied prospectively. This treatment allowed them full weightbearing
      after approx. 9 days, the average time of sick-leave was 19 days. Longterm
      results showed no complications. The majority of patients (92%) were satisfied
      with this treatment. We consider the early functional treatment of a fracture of
      the base of the fifth metatarsal bone with an orthopedic boot as a reliable and
      cost effective treatment.

PMID- 9190284
TI  - [The value of diagnostic peritoneal lavage in emergency situations].
AB  - PURPOSE: The literature on diagnostic peritoneal lavage in the assessment of
      blunt abdominal trauma reflects an ongoing controversy. Therefore we conducted a
      prospective evaluation of the diagnostic management of blunt abdominal trauma
      used at our clinic, in which this procedure plays a substantial role. During the
      years 1993 and 1994 a total of 75 patients could be included in the study. The
      study population consisted of all patients with a diagnosis of blunt abdominal
      trauma. In addition, all trauma patients who were unresponsive on admission to
      the emergency receiving unit underwent the same program of diagnostic work-up.
      This group included polytraumatized patients, patients with craniocerebral
      injuries and all those who had been intubated prior to admission. Patients with
      stable vital signs were evaluated first by sonography of the abdomen, whereas
      those showing signs of hypovolemic shock received a diagnostic peritoneal lavage
      as the first evaluation of abdominal trauma. In order to assess the relative
      value of the two diagnostic methods, all patients who had had ultrasound as their
      first examination subsequently also underwent peritoneal lavage. RESULTS: 37
      patients (49%) had lavage evidence of intraperitoneal bleeding. Of these 22 (29%
      of the total) subsequently underwent emergency laparotomy with lesions requiring
      surgical treatment found in 21 (95%). Only in one patient (1.3% of the study
      population) laparotomy failed to reveal a lesion requiring surgical correction.
      The accuracy of peritoneal lavage findings as an indication for laparotomy was
      99%, compared to 82% for ultrasonography used as a initial diagnostic procedure.
      Diagnostic peritoneal lavage is quick, safe and almost independent of the
      experience of the investigating physician. It can be performed during other
      diagnostic procedures and can be repeated at will. If beyond macroscopical
      evaluation the lavage fluid is assessed chemically, even duodenal and pancreatic
      lesions as well as injuries to other hollow viscera can be suspected. With a
      sensitivity of 100% and a specificity of 98%, diagnostic peritoneal lavage is an
      extremely reliable diagnostic tool. It should be used as the initial diagnostic
      procedure in all hypovolemic and/or unresponsive patients suspected of having
      suffered blunt abdominal trauma. In conscious patients with stable vital signs,
      ultrasonography can be used for initial diagnosis. It should, however, be
      complemented by subsequent peritoneal lavage whenever the clinical course gives
      rise to suspicion.

PMID- 9190285
TI  - Consensus chemistry and beta-turn conformation of the active core of the insect
      kinin neuropeptide family.
AB  - BACKGROUND: Neuropeptides are examples of small, flexible molecules that bind to
      receptors and induce signal transduction, thereby eliciting biological activity.
      The multifunctional insect kinin neuropeptides retain full activity when reduced
      to only their carboxy-terminal pentapeptide (Phe1-X2-X3-Trp4-Gly5-NH2), thereby
      allowing extensive structure-function studies and conformational analysis.
      RESULTS: A combined experimental and theoretical analysis of the insect kinin
      carboxy-terminal pentapeptide was used to probe the role of each residue, define
      the bioactive conformation, and design a constrained bioactive analog. Coupling
      receptor-binding data with two biological activity assays allowed receptor
      binding and signal transduction to be differentiated. A preferred beta-turn
      conformation, found for residues 1-4 by molecular dynamics simulations, was
      tested by designing a conformationally restricted cyclic hexapeptide. This cyclic
      analog showed a preference for the beta-turn conformation, as shown by a
      conformational search and nuclear magnetic resonance spectroscopy, and it showed
      stronger receptor binding but decreased activity relative to highly active linear
      analogs. CONCLUSIONS: Each residue of the insect kinin carboxy-terminal
      pentapeptide has a distinct role in conformational preference, specific receptor
      interactions or signal transduction. The beta-turn preference of residues Phe1-X2
      X3-Trp4 implicates this as the bioactive conformation. The amidated carboxyl
      terminus, required for activity in many neuropeptide families, may be generally
      important for signal transduction and its inclusion may therefore be essential
      for agonist design.

PMID- 9190286
TI  - Observation of metastable Abeta amyloid protofibrils by atomic force microscopy.
AB  - BACKGROUND: Brain amyloid plaque, a diagnostic feature of Alzheimer's disease
      (AD), contains an insoluble fibrillar core that is composed primarily of variants
      of the beta-amyloid protein (Abeta). As Abeta amyloid fibrils may initiate
      neurodegeneration, the inhibition of fibril formation is a possible therapeutic
      strategy. Very little is known about the early steps of the process, however.
      RESULTS: Atomic force microscopy was used to follow amyloid fibril formation in
      vitro by the Abeta variants Abeta1-40 and Abeta1-42. Both variants first form
      small ordered aggregates that grow slowly and then rapidly disappear, while
      prototypical amyloid fibrils of two discrete morphologies appear. Abeta1-42
      aggregates much more rapidly than Abeta1-40, which is consistent with its
      connection to early-onset AD. We propose that the metastable intermediate species
      be called Abeta amyloid protofibrils. CONCLUSIONS: Abeta protofibrils are likely
      to be intermediates in the in vitro assembly of Abeta amyloid fibrils, but their
      in vivo role has yet to be determined. Numerous reports of a nonfibrillar form of
      Abeta aggregate in the brains of individuals who are predisposed to AD suggest
      the existence of a precursor form, possibly the protofibril. Thus, stabilization
      of Abeta protofibrils may be a useful therapeutic strategy.

PMID- 9190287
TI  - FR900482, a close cousin of mitomycin C that exploits mitosene-based DNA cross
      linking.
AB  - BACKGROUND: The class of antitumor antibiotics that includes FR900482 has a very
      close structural analogy to the mitomycins, one of which, mitomycin C, has been
      in widespread clinical use for more than 20 years. Like mitomycin C, these
      antitumor antibiotics are reductively activated in vivo and covalently cross-link
      DNA as a result of activity of the mitosene moiety generated on reduction. Owing
      to differences in structure and the attendant mechanistic differences in
      bioreductive activation between the mitomycins and FR900482, FR900482 does not
      produce an adventitious superoxide radical anion during reductive activation and
      thus does not exhibit oxidative strand scission of DNA. It is postulated that the
      low clinical toxicity of FR900482 relative to mitomycin C is a direct
      manifestation of the mechanistic differences of bioreductive activation leading
      to the highly reactive DNA cross-linking mitosenes. RESULTS: Using Fe(II)-EDTA
      footprinting, we showed that the two natural products FR900482 (1) and dihydro,
      FR66979 (3), and the semi-synthetically derived triacetate FK973 (2), display
      remarkable selectivity for 5' deoxy-CG sequences of DNA, and that this
      selectivity is abolished upon deletion of the exocyclic N2 amine of either
      participating guanosine residue. In addition, we investigated the mono alkylation
      abilities of FR66979 with respect to a number of inosine-substituted
      oligonucleotides and observed that the FR900482 class of compounds were able to
      give rise to easily separable orientation isomers of their respective cross
      links. CONCLUSIONS: The FR900482 class of antitumor antibiotics cross-link DNA in
      a fashion analogous to the mitomycins. The cross-linking reaction yields two
      orientation isomers which are of vastly different electrophoretic mobility and
      which also exhibit radically different DNA-protein recognition properties upon
      reaction with AluI restriction endonuclease. In addition, mono-alkylation of DNA
      by FR66979 shows little, if any, dependence upon pre-covalent interactions deemed
      necessary for the mitomycins. These insights support the proposal that the
      FR900482 class of compounds represents a compelling clinical replacement for
      mitomycin C, given its greatly reduced host toxicity and superior DNA interstrand
      cross-linking efficacy.

PMID- 9190288
TI  - Leptomycin B is an inhibitor of nuclear export: inhibition of nucleo-cytoplasmic
      translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and
      Rev-dependent mRNA.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) regulatory protein
      Rev is required for unspliced and incompletely spliced viral mRNAs to appear in
      the cytoplasm and thus for viral replication. Translocation of Rev from the
      nucleus to the cytoplasm is essential if Rev is to function. We wanted to
      identify inhibitors of this transport process because they would be potential
      antiviral agents. RESULTS: The Streptomyces metabolite, leptomycin B, and other
      antibiotics of the leptomycin/kazusamycin family were identified as inhibitors of
      the nucleo-cytoplasmic translocation of Rev at nanomolar concentrations. Rev
      dependent export of mRNA into the cytoplasm is also blocked by leptomycin B,
      which inhibits Rev-dependent, but not Rev-independent gene expression in a short
      term transfection assay. In primary human monocytes, leptomycin B suppresses HIV
      1 replication. CONCLUSIONS: Leptomycin B is the first low molecular weight
      inhibitor of nuclear export to be identified. Although it cannot be used
      therapeutically, it should serve as a valuable tool for dissecting nuclear export
      pathways.

PMID- 9190289
TI  - A combinatorial approach for determining protease specificities: application to
      interleukin-1beta converting enzyme (ICE).
AB  - BACKGROUND: Interleukin-1beta converting enzyme (ICE/caspase-1) is the protease
      responsible for interleukin-1beta (IL-1beta) production in monocytes. It was the
      first member of a new cysteine protease family to be identified. Members of this
      family have functions in both inflammation and apoptosis. RESULTS: A novel method
      for identifying protease specificity, employing a positional-scanning substrate
      library, was used to determine the amino-acid preferences of ICE. Using this
      method, the complete specificity of a protease can be mapped in the time required
      to perform one assay. The results indicate that the optimal tetrapeptide
      recognition sequence for ICE is WEHD, not YVAD, as previously believed, and this
      led to the synthesis of an unusually potent aldehyde inhibitor, Ac-WEHD-CHO (Ki =
      56 pM). The structural basis for this potent inhibition was determined by X-ray
      crystallography. CONCLUSIONS: The results presented in this study establish a
      positional-scanning library as a powerful tool for rapidly and accurately
      assessing protease specificity. The preferred sequence for ICE (WEHD) differs
      significantly from that found in human pro-interleukin-1beta (YVHD), which
      suggests that this protease may have additional endogenous substrates, consistent
      with evidence linking it to apoptosis and IL-1alpha production.

PMID- 9190290
TI  - A new class of models for computing receptor-ligand binding affinities.
AB  - Models for predicting the binding affinities of molecules in solution are either
      very detailed, making them computationally intensive and hard to test, or very
      simple, and thus less informative than one might wish. A new class of models that
      focus on the predominant states of the binding molecules promise to capture the
      essential physics of binding at modest computational cost.

PMID- 9190291
TI  - Discriminating among the discriminator bases of tRNAs.
AB  - Aminoacyl-tRNA synthetases must select their specific tRNAs from the 20
      structurally similar tRNAs present in a cell. The discriminator base, at position
      73 of the tRNA, is important for this selection but its effects on aminoacylation
      are variable depending on context. Recent structural studies provide insight into
      this variability.

PMID- 9190293
TI  - Reply to A.R.Green--narrative, history and accuracy.

PMID- 9190292
TI  - Glycosphingolipid antigens and cancer therapy.
AB  - Specific types of glycosphingolipid (GSL), which are chemically detectable in
      normal cells, are more highly expressed in tumors. The high level of expression
      on the surfaces of tumor cells causes an antibody response to these GSLs, which
      can therefore be described as tumor-associated antigens. Some of these GSLs have
      been shown to be adhesion molecules involved in tumor cell metastasis, and to be
      modulators of signal transduction controlling tumor cell growth and motility.
      Tumor-associated GSL antigens have been used in the development of antitumor
      vaccines. GSLs and sphingolipids involved in adhesion and signaling are therefore
      targets for cancer therapy.

PMID- 9190294
TI  - Antibiotic resistance in respiratory tract pathogens: clinical and therapeutic
      consequences. Proceedings of a symposium. Stockholm, Sweden, October 31-November
      1, 1994.

PMID- 9190295
TI  - The envelope in bacterial physiology and antibiotic action. Part I. Proceedings
      of a symposium. Verona, Italy, September 10-14, 1995. To the memory of Professor
      Giuseppe Satta.

PMID- 9190296
TI  - The envelope in bacterial physiology and antibiotic action. Part II. Proceedings
      of a symposium. Verona, Italy, September 10-14, 1995.

PMID- 9190297
TI  - Glutaraldehyde-resistant Mycobacterium chelonae from endoscope washer
      disinfectors.
AB  - Glutaraldehyde is used to disinfect flexible and other heat-sensitive endoscopes
      often with the aid of automated systems. Mycobacterium chelonae is being isolated
      with increasing frequency from these washer disinfectors and processed
      endoscopes. This has, on occasions, led to misdiagnosis and iatrogenic
      infections. Recent reports suggest that disinfecting machines, on a sessional or
      regular basis, with 2% glutaraldehyde may have selected and therefore encouraged
      the growth of strains of Myco. chelonae, possibly in biofilm, with decreasing
      susceptibility to glutaraldehyde. In view of this, the resistance of three
      strains of Myco. chelonae var. chelonae (the type strain NCTC 946 and two machine
      isolates) was tested against 2% glutaraldehyde and a wide range of alternative
      disinfectants. Disinfectants tested were a chlorine releasing agent, sodium
      dichloroisocyanurate at 1000 ppm and 10,000 ppm av Cl, 0.35% peracetic acid
      (NuCidex, Johnson & Johnson), 70% industrial methylated spirit (IMS), 1%
      peroxygen compound ('Virkon', Antec International) and 10% succine dialdehyde
      ('Gigasept', Sanofi Winthrop). Suspension and carrier tests were carried out in
      the presence and absence of an organic load. Results showed the type strain,
      which had not been exposed to the selective pressure of disinfectant usage, to be
      very sensitive to most disinfectants with the exception of 1% Virkon. The washer
      disinfector isolates, on the other hand, were extremely resistant to 2%
      glutaraldehyde and showed greater resistance to 1% Virkon and 1000 ppm NaDCC.
      Purchasing machines in which the entire fluid pathways, including those for
      delivering rinse water, are disinfected with an appropriate agent during each
      cycle are preferred. If this is not possible then sessional cleaning and
      disinfection at the start of each day and regular maintenance should prevent
      biofilm formation and contamination with disinfectant-resistant strains of
      mycobacteria. In addition to machine disinfection, the use of sterile or bacteria
      free (filtered < 0.45 microm) water is essential for bronchoscopes and all
      invasive endoscopes. If there is doubt that the effectiveness of the machine
      disinfection procedure or water quality, the channels and surfaces of endoscopes
      may be rinsed with 70% IMS after automated processing.

PMID- 9190298
TI  - 6th International Symposium for Health Professionals in Rheumatology. Pellenberg,
      Belgium, 19-21 September 1996. Abstracts.

PMID- 9190300
TI  - [Lymphedema after breast carcinoma. A study of 5868 cases].
AB  - BASIC PROBLEM AND OBJECTIVE: According to published reports, the incidence of
      lymphoedema of the arm in patients with cancer of the breast, treated by either
      surgery or radiotherapy, varies widely. We obtained basic data on the treatment
      of breast cancer in a large number of patients in order to determine the
      relationship between the incidence of lymphoedema and the radical nature of the
      primary treatment. PATIENTS AND METHODS: Data were collected on all women with
      lymphoedema of the arm after treatment for breast cancer between 1972 and 1995.
      The increase in arm circumference was measured by a standardised method. Only
      those patients were included in the final analysis whose arm circumference had
      increased by at least 2 cm. The type of operation and(or) radiotherapy, tumor
      histology and TNM classification were recorded. RESULTS: There were 1405 cases of
      arm lymphoedema after treatment of 5868 cases of breast cancer (24%). 2515 breast
      cancers had been treated surgically. 3353 surgically and by radiotherapy.
      Lymphoedema occurred in 22.3% after radical mastectomy without radiotherapy and
      in 44.4% with it; after modified radical mastectomy without radiotherapy in
      19.1%, in 28.9% with radiotherapy; after breast-preserving operation without
      radiotherapy in 6.7%, with radiotherapy in 10.1%. Until the 1970s radical
      mastectomy with conventional postoperative radiotherapy has been the treatment of
      choice, with 38% cases of lymphoedema. This incidence gradually decreased to 16%
      in subsequent years. CONCLUSION: The incidence of lymphoedema of the arm depends
      on the radical nature of the primary treatment. The quality of life could be
      easily improved through minimising the incidence of lymphoedema if current
      standards of breast-preserving surgery were generally practised.

PMID- 9190299
TI  - [Ambulatory therapy of multiple myeloma with vincristine, adriamycin and
      dexamethasone].
AB  - BACKGROUND AND OBJECTIVE: If multiple myeloma (MM) progresses in patients after
      chemotherapy with alkylating agents, the combination of vincristine, adriamycin
      and dexamethasone (VAD) can achieve a response in 40-70% of cases. Because of its
      low toxicity for haematopoetic stem-cells this form of chemotherapy is often
      undertaken before high-dose blood stem-cell transplantation. It was the objective
      of this study to examine effectiveness and complications of ambulant VAD
      treatment. PATIENTS AND METHODS: Within four years VAD chemotherapy was given to
      62 ambulant MM patients, administered by microprocessor-regulated pumps via
      intravenously polyurethane catheters with a safety valve. Response to treatment,
      treatment-associated complications and infections were documented prospectively
      and analysed. RESULTS: VAD treatment achieved tumour reduction of more than 25%
      in 50 of 62 patients. This treatment had to be discontinued in two of 192 pump
      infusions because of irreversible catheter occlusion. Eight patients were
      hospitalised because of infections and two for noninfectious complications.
      Severe infectious complications (> or = WHO grade III) occurred in 4% of
      treatment cycles. CONCLUSION: VAD chemotherapy can be performed with a low rate
      of infection in ambulant patients despite the need for prolonged intravenously
      infusion of the drugs. But to avoid complications by intravenously catheters,
      random prospective tests should first be done with oral alkylating agents.

PMID- 9190301
TI  - [Mycoplasma hominis. A rare causative agent of acute pyelonephritis].
AB  - HISTORY AND CLINICAL FINDINGS: A 23-year-old woman was admitted with typical
      signs of an acute urinary tract infection: fever, pain on tapping over both renal
      areas and in both flanks, urgency and dysuria. She had a history of renal colic
      with spontaneous passage of a renal stone. INVESTIGATIONS: There was marked
      leukocytosis and raised C-reactive protein, leukocyturia and haematuria, but no
      nitrites or protein in the urine. All blood and urine cultures were sterile and
      renal ultrasound was unremarkable. DIAGNOSIS, TREATMENT AND COURSE: As signs and
      laboratory data indicated acute pyelonephritis (PN) she was treated with gyrase
      inhibiting antibiotics. But while symptoms improved, fever, leukocyturia and
      haematuria continued; no micro-organism could be demonstrated. Mycoplasma was
      therefore considered as a rare cause of PN. Special urine cultures then grew M.
      hominis, > 10(5) organisms/ml. On the basis of sensitivity tests doxycycline was
      administered. All symptoms quickly improved and all inflammation parameters and
      urine sediments became normal. CONCLUSION: In rare instances M. hominis may be
      isolated as the causative organism of PN. If, in cases with appropriate symptoms,
      routine tests fail to demonstrate the causative agent, M. hominis should be
      included in the differential diagnosis.

PMID- 9190302
TI  - [The diagnosis of dyskinesias of Oddi's sphincter].

PMID- 9190303
TI  - [Heart tumors--their manifestation through uncharacteristic symptoms].

PMID- 9190304
TI  - [Holism and medicine].

PMID- 9190305
TI  - [Cryofibrinogenemia caused by monoclonal antifibrinogen antibodies. Pseudo
      cryofibrinogenemia].

PMID- 9190306
TI  - [Periodic paralysis as the first manifestation of hyperthyroidism].

PMID- 9190307
TI  - [The decision for complementary medicine--fact-oriented or irrational?].

PMID- 9190308
TI  - [The significance of risk-adapted antiviral prophylaxis and modern virus
      diagnosis for organ survival after kidney transplantation].
AB  - BASIC PROBLEM AND OBJECTIVE: Viral, especially cytomegalovirus (CMV), infections
      are after rejection reaction the most serious problem following organ
      transplantation. The risk of disease correlates with the CMV donor/recipient
      constellation and the degree of immunosuppression. The importance of antiviral
      prophylaxis remains unresolved. Whether drug prophylaxis adapted to the
      individual risk is of clinical value was investigated in a prospective study.
      PATIENTS AND METHODS: A risk-adapted stepwise antiviral prophylactic regimen was
      given to 62 patients with renal transplants. All patients at risk of CMV
      infection were given acyclovir, 200 mg four times daily for 3 months. Patients
      with rejection reaction for which they were receiving i.v. immunosuppressive
      treatment additionally received CMV hyperimmunoglobulin (2 ml/kg body weight on
      days 1 and 14). High-risk patients (donor CMV positive and recipient CMV
      negative) were given as basic prophylaxis CMV hyperimmunoglobulin i.v. on days 1
      and 14 after transplantation, and additionally i.v. ganciclovir during any
      rejection treatment. The results were compared with those of a retrospectively
      selected patient cohort (n = 52) who had received only acyclovir as basic
      prophylaxis. The diagnosis of CMV infection was made by demonstrating CMVpp65
      antigen in blood. In the prospectively studied patients measurement of beta 2
      microglobulin concentration was used to determine viruria in 24-hour urine.
      RESULTS: Among the high-risk group (donor CMV positive/recipient CMV negative)
      the additional prophylactic regimen significantly reduced the proportion of CMV
      associated cases of rejection (14% compared with 42%, P < 0.05) in the basic
      prophylaxis only group. Similar results were obtained for CMV-caused transplant
      loss within the first 3 years (19% vs 50%, P < 0.05). The additional prophylaxis
      had no influence on the incidence of CMV infection. In case of active infection
      an isolated rise of beta 2-microglobulin in urine occurred in active infection at
      a mean of 6 days before CMVpp65 antigenaemia (sensitivity of 89%). CONCLUSIONS:
      These results indicate that risk-adapted antiviral prophylaxis can decisively
      influence the long-term prognosis for a renal transplant, but not the incidence
      of CMV infection. The early and reliable diagnosis of active CMV infection is
      made possible by the combined use of beta 2-microglobulinuria and pp65
      antigenaemia.

PMID- 9190310
TI  - [Stents for the palliative treatment of malignant gastric outlet stenoses].
AB  - HISTORY: Two patients were admitted because of subtotal gastric outlet
      obstruction. In case 1, a 56-year-old man, who 16 months previously had undergone
      a pancreatic resection and Billroth II gastrectomy for pancreatic carcinoma,
      started to vomit due to a subtotal obstruction at the Billroth II anastomosis. In
      case 2, a 53-year-old woman with incurable metastasising gall-bladder carcinoma
      was seven months later found to have almost complete obstruction in the
      postgastric portion of the duodenum. Both patients vomited even after liquid food
      and had to be fed intravenously. FINDINGS: Radiology revealed some markedly
      twisted and high-grade stenoses in the postgastric small intestine. TREATMENT AND
      COURSE: In the first patient (postgastrectomy) a wall stent, 10 cm long and 2.2
      cm in diameter, was placed across the stenosis without difficulty. In the other
      patient a similar stent was placed, but with great difficulty. Both patients were
      afterwards able to eat normal food without problem. CONCLUSION: Even when normal
      gastric anatomy has been preserved endoscopic placement of a stent can provide
      optimal results without surgery. Further advances will be achieved without great
      expense by further improving the equipment used for introducing the stent.

PMID- 9190311
TI  - [Diagnostic imaging of hepatocellular carcinoma].

PMID- 9190309
TI  - [Neonatal Basedow's disease in twins from a mother with severe T3
      hyperthyroidism].
AB  - HISTORY AND CLINICAL FINDINGS: Dizygotic twin sisters were born to a woman who,
      shortly before becoming pregnant, had developed Graves' disease with markedly
      elevated triiodothyronine (T3) levels and highly positive TSH receptor antibody
      titres (TRAb: 169 mU/ml). From the second week of life onwards they had a goitre
      and hyperexcitability, tachycardia and failure to thrive were noted. In addition,
      twin I had mild exophthalmos. As thyrostatic treatment of the mother was very
      difficult, intrauterine hypothyroidism or transitory hyperthyroidism had
      presumably occurred in the twins. INVESTIGATIONS: Twin I had maximal thyroxine
      (T4) concentration of 26.2 micrograms/dl, while it was 24.7 micrograms/dl in twin
      II with suppressed TSH. Both twins had high concentrations of TRAb and antibodies
      against thyroid peroxidase. DIAGNOSIS, TREATMENT AND COURSE: With the diagnosis
      of neonatal Graves' disease established, both twins were treated with propranolol
      (2 mg/kg.d) and phenobarbitone (2-4 mg/kg.d). Twin I, whose symptoms were more
      severe, also received propylthiouracil (5 mg/kg.d) until euthyroidism had been
      achieved. Although twin II became euthyroid spontaneously, she gained weight only
      slowly and microcephaly developed together with definite motor and mental
      retardation. It remains unclear whether these were consequences of intrauterine
      hypothyroidism or post-partum hyperthyroidism. CONCLUSION: Graves' disease during
      pregnancy demands interdisciplinary collaboration between gynaecologist,
      physician and paediatrician to prevent severe sequelae in the children. Early
      risk assessment is possible by measuring the TSH receptor antibody titre in
      umbilical blood.

PMID- 9190312
TI  - [Meta-analysis].

PMID- 9190313
TI  - [Intensive care precautions for brain-dead pregnant women in law and ethics].

PMID- 9190314
TI  - [Otothermometry].

PMID- 9190315
TI  - [Hypoplasia of the left heart ventricle--casuistic contribution to the
      development of this heart malformation].
AB  - The case report describes and compares an univentricular heart of a calf with
      hypoplasias of left ventricles of two further calves and a newborn moufflon. In
      all cases there is also stenosis of the aortic arch. The functional effects of
      the malformations are discussed. The hypothesis is proposed that an
      univentricular heart may be the extreme variant of hypoplasia of the left heart
      when there is an additional aortic stenosis.

PMID- 9190316
TI  - [Frequency and etiology of calf losses and calf diseases in cow-calf farms. I.
      Methods of data collection, calf mortality, and calf morbidity].
AB  - An observational study was initiated to provide general information on calf
      health and estimates of frequency and of economic impact of calf diseases in
      farms with extensive beef production. The study was planned as a cohort study and
      included all calves born during the calving season of 1993/94 in 105 cow-calf
      farms in western Switzerland. The total preweaning mortality was 8.5% (123 calves
      out of 1452 calvings); 2.5% of the calves were stillborn, and 6.0% died or were
      euthanized before weaning. Forty-four percent of all losses were recorded in the
      perinatal period (i.e. the first 48 hours p. p.). The average preweaning
      mortality among liveborn calves at farm level was 6.1%. A large variation in
      mortality was observed from farm to farm (0-50%). In 50% of the post mortem
      analyses, respiratory disease was diagnosed as the cause of death. Twenty-two
      percent of all calves were treated at least once by a veterinarian. Thirty-six
      percent of all treatments were performed because of diarrhea, 26% because of
      respiratory disease and 15% because of umbilical problems. From birth to weaning
      age, the average treatment costs including calving assistance, medication and
      prophylactic measures were SFr, 23.80 per calf.

PMID- 9190317
TI  - [Space required for sheep during transport].
AB  - Space required for different body, positions was investigated for sheep of
      different weight and genetic background in undisturbed housing conditions. Body
      temperature, as stress indicator, was measured at different intervals during
      transport. The loading situation caused a distinct increase; a slight increase
      was measured after unloading. During transport, the values did not reach those
      taken before loading. Concerning the space required for resting, the present
      results indicate that sheep (weighing between 32 and 35 kg) being transported
      with a space allowance of 0.16, 0.26, 0.27, 0.42 and 0.45 m2/animal showed an
      appreciable amount of resting behaviour only at lower densities, i.e. with space
      allowance of more than 0.40 m2. The recommended space allowance by the EU of 0.21
      to 0.23 m2 for sheep of this weight group has to be considered as too low to
      permit effective resting behaviour. The problem of supplying sheep with water and
      feed during transport has not yet been solved. The question is not only how much
      space the animals need for feeding but also a matter of the technical equipment
      for supplying feed and water so that all animals are able to reach it.

PMID- 9190318
TI  - [Case report: tympany and diarrhea in calves].
AB  - Diarrhoea and meteorism was observed in calves, that were fed on hay, linseed and
      milk replacer. Different factors were found in the feedstuffs, which could have
      caused these symptoms. The feeding value of the hay was not high enough due to
      intense lignification, while the milk replacer showed a slightly impaired
      hygienic quality. The linseed contained cyanogenic glycosides in higher
      concentrations (226 mg HCN/kg).

PMID- 9190319
TI  - [The complexity of physiopharmacologic aspects of pain].
AB  - Understanding pain or, more precisely, the different types of pain, is above all
      a question of understanding its physiological mechanisms and, in this regard, the
      role of basic research has without doubt been to trigger the development of new
      therapeutic strategies. In an approach to these problems, the main international
      teams involved in pain research have attempted to develop models of experimental
      pain in rats. Clearly, research aimed at developing these models is controlled by
      certain ethical considerations; however, in this context, the end must surely
      justify the means. The main models used (acute or chronic inflammation,
      rheumatoid arthritis, peripheral neuropathy) certainly do not give a
      comprehensive representation of all the pain syndromes encountered in clinical
      practice, but they do provide new data concerning the physiological, behavioural
      and pharmacological aspects of pain. While giving a brief description of the
      complexity of the pain circuit, this article also makes reference to certain
      pharmacological approaches to the treatment of pain. Peripheral nociceptive
      messages are conveyed by a mosaic of unmyelinated free fibres distributed
      throughout cutaneous, muscular and articular tissue, and within the visceral
      walls. They are then transmitted via various nerve endings (polymodal
      nociceptors) by small diameter A delta and C fibres, which are activated by
      mechanical, thermal and chemical stimuli. It is nevertheless difficult to
      ascertain whether these small diameter fibres are involved only in nociception
      (specific nociceptors) or whether pain causes an excessive activation of these
      receptors, which under normal conditions have a role in the reflex that regulates
      various functions (nonspecific nociceptors). Numerous chemical substances play a
      part in generating nociceptive impulses (e.g. histamine, serotonin,
      prostaglandins). Furthermore, the role of neuropeptides, such as calcitonin gene
      related peptide and particularly substance P, has been clearly demonstrated in
      the activation of early neurogenic inflammation. Other substances, such as
      bradykinin and cytokines, are involved in prolonging the sensation of pain. Nerve
      growth factor also prolongs the sensation of pain by increasing the cellular
      excitability of nociceptors and promoting the action of the sympathetic nervous
      system, which has a major role in controlling pain. The very great diversity of
      all these interacting substances makes the pharmacological treatment of pain
      extremely complex. Nevertheless, new therapeutic advances are providing
      interesting approaches, particularly the development of specific inhibitors of
      cyclo-oxygenase 2 (COX 2), which is produced by the inflammatory process. Such
      inhibitors would preserve COX 1, which is both constitutive and physiological,
      and thereby provide improved tolerability compared with currently used NSAIDs,
      which act upon both COX pathways. A major focus of research relating to new
      analgesics is the development of synthetic antagonists of bradykinin, substance P
      and N-methyl-D-aspartate receptors. An improved understanding of anatomical and
      electrophysiological processes has led to the discovery of new ascending pathways
      that transmit nociceptive messages to the reticular formation, the hypothalamus,
      and the amygdala, as well as to certain areas of the cortex. As a result the
      notion of one single pain centre is no longer valid. This idea is further
      reinforced by the knowledge that, at different stages of the pain pathway,
      different control systems constantly modulate the transmission of nociceptive
      information. Consequently, at a spinal level, activation of the large diameter
      cutaneous fibres (A alpha et beta) blocks pain stimuli transmitted by the small
      diameter fibres. Knowledge of this "gate control' mechanism of the posterior horn
      of the spinal cord is put to practical application in treatments involving
      transcutaneous electrical nerve stimulation. (ABSTRACT TRUNCATED)

PMID- 9190320
TI  - [Review of current pharmacologic treatment of pain].
AB  - Pain is the main reason prompting patients to consult their physicians. In acute
      conditions, pain has a very particular significance as a warning sign, enabling
      the physician to attempt a diagnosis. Nevertheless, its detrimental effect upon
      the individual (even in the case of acute pain) and its cost to society are now
      widely acknowledged. There can be no doubt about the physical component of pain,
      but the psychological and social aspects should not be ignored, particularly in
      the case of chronic pain. There is no single therapeutic approach to pain and,
      more often than not, successful treatment comprises a combination of several.
      Pharmacological treatments are undeniably the most common approach. In clinical
      practice, recent advances have been based upon an improved understanding of 'old'
      substances such as morphine and, at the same time, research continues in the hope
      of finding the 'ideal' analgesic-effective in most situations but without adverse
      effects: this appears to be a somewhat utopian arm at present, considering the
      number of different causes of pain. An improved understanding of the
      physiological mechanisms of pain has led, within the field of clinical practice,
      to several methods of differentiating pain. These depend on whether or not pain
      responds to morphine, or on the type of pain: pain due to an excess of
      nociception, pain resulting from deafferentation (caused by damage to nerve
      pathways) in the central or peripheral nervous system and psychogenic
      (idiopathic) pain. Likewise, there are several different ways of classifying
      analgesic treatments: according to the intensity of pain, as with use of the WHO
      ladder (which is based on the notion of steps) for the treatment of cancer pain;
      according to the presumed physiopathological mechanism and, in particular, the
      response to morphine, and according to the presumed central or peripheral
      mechanism of the drugs. In reality, peripherally acting drugs can also have a
      central mechanism of action, just as drugs known to have a central mechanism of
      action can also have peripheral activity. As a result, several therapeutic
      classes have been identified. Firstly NSAIDs, which act by inhibiting the enzymes
      that synthesise prostaglandins, cyclooxygenases (COX-1, COX-2), but which also
      act upon lipo-oxygenases: Their efficacy is interesting, although somewhat
      limited by both their ceiling effect and the frequent adverse gastrointestinal
      reactions they produce. Specific inhibitors of COX-2 could well reduce the risk
      of adverse effects. Opioids constitute the first-line treatment for pain,
      particularly severe pain. There are several classifications for these drugs.
      Firstly, weak opioids (such as codeine) and strong opioids (such as morphine) are
      differentiated. Secondly, a distinction is made between pure agonists (such as
      morphine), partial agonists (such as buprenorphine), agonist-antagonists (such as
      nalbuphine) and antagonists (such as naloxone). Finally, agents are distinguished
      on the basis of their chemical structure (synthetic, semi-synthetic or natural
      derivatives). These molecules act upon different receptors (mu, delta, kappa,
      sigma) and, although peripheral mechanisms have been described, their activity
      occurs mainly at spinal and supraspinal levels. They provide a potent analgesic
      effect but are also responsible for various adverse effects-nausea, vomiting,
      sedation, constipation and respiratory depression-which seriously limit their
      use. As long as the indication is appropriate, these drugs should not be withheld
      because of fear of dependence or abuse. It has been observed that other adjuvant
      therapeutic approaches, generally used to treat conditions other than pain,
      provide pain relief in certain situations. These include corticosteroids, which
      are-widely used in rheumatology and oncology, and antidepressants, which are
      frequently used to treat chronic pain, especially that with a neuropathic
      component. Anti-epileptics are also used, particularly for excrutiating

PMID- 9190321
TI  - [Pharmacology of tramadol].
AB  - (+/-)-Tramadol is a synthetic 4-phenyl-piperidine analogue of codeine. It is a
      central analgesic with a low affinity for opioid receptors. Its selectivity for
      mu receptors has recently been demonstrated, and the M1 metabolite of tramadol,
      produced by liver O-demethylation, shows a higher affinity for opioid receptors
      than the parent drug. The rate of production of this M1 derivative (O-demethyl
      tramadol), is influenced by a polymorphic isoenzyme of the debrisoquine-type,
      cytochrome P450 2D6 (CYP2D6). Nevertheless, this affinity for mu receptors of the
      CNS remains low, being 6000 times lower than that of morphine. Moreover, and in
      contrast to other opioids, the analgesic action of tramadol is only partially
      inhibited by the opioid antagonist naloxone, which suggests the existence of
      another mechanism of action. This was demonstrated by the discovery of a
      monoaminergic activity that inhibits noradrenaline (norepinephrine) and serotonin
      (5-hydroxytryptamine; 5-HT) reuptake, making a significant contribution to the
      analgesic action by blocking nociceptive impulses at the spinal level. (+/-)
      Tramadol is a racemic mixture of 2 enantiomers, each one displaying differing
      affinities for various receptors. (+/-)-Tramadol is a selective agonist of mu
      receptors and preferentially inhibits serotonin reuptake, whereas (-)-tramadol
      mainly inhibits noradrenaline reuptake. The action of these 2 enantiomers is both
      complementary and synergistic and results in the analgesic effect of (+/-)
      tramadol. After oral administration, tramadol demonstrates 68% bioavailability,
      with peak serum concentrations reached within 2 hours. The elimination kinetics
      can be described as 2-compartmental, with a half-life of 5.1 hours for tramadol
      and 9 hours for the M1 derivative after a single oral dose of 100mg. This
      explains the approximately 2-fold accumulation of the parent drug and its M1
      derivative that is observed during multiple dose treatment with tramadol. The
      recommended daily dose of tramadol is between 50 and 100mg every 4 to 6 hours,
      with a maximum dose of 400 mg/day; the duration of the analgesic effect after a
      single oral dose of tramadol 100mg is about 6 hours. Adverse effects, and nausea
      in particular, are dose-dependent and therefore considerably more likely to
      appear if the loading dose is high. The reduction of this dose during the first
      days of treatment is an important factor in improving tolerability. Other adverse
      effects are generally similar to those of opioids, although they are usually less
      severe, and can include respiratory depression, dysphoria and constipation.
      Tramadol can be administered concomitantly with other analgesics, particularly
      those with peripheral action, while drugs that depress CNS function may enhance
      the sedative effect of tramadol. Tramadol should not be administered to patients
      receiving monoamine oxidase inhibitors, and administration with tricyclic
      antidepressant drugs should also be avoided. Tramadol has pharmacodynamic and
      pharmacokinetic properties that are highly unlikely to lead to dependence. This
      was confirmed by various controlled studies and postmarketing surveillance
      studies, which reported an extremely small number of patients developing
      tolerance or instances of tramadol abuse. Tramadol is a central acting analgesic
      which has been shown to be effective and well tolerated, and likely to be of
      value for treating several pain conditions (step II of the World Health
      Organization ladder) where treatment with strong opioids is not required.

PMID- 9190322
TI  - [Tramadol in acute pain].
AB  - Tramadol has been in clinical use in Germany since the late 1970s and has proven
      effective in both experimental and clinical pain without causing serious
      cardiovascular or respiratory side effects. Moreover, the negligible abuse
      potential of tramadol has meant that it has never been a restricted drug, and it
      therefore very quickly became the most popular analgesic of its class in Germany.
      Although tramadol has been used in myocardial emergencies, in trauma and
      obstetric pain, or to supplement balanced anaesthesia, most studies have
      investigated postoperative patients. The focus of this article is to review
      clinical experience with tramadol in the treatment of acute postoperative pain.
      Tramadol, a synthetic opioid of the aminocyclohexanol group, is a centrally
      acting analgesic with weak opioid agonist properties, and effects on
      noradrenergic and serotonergic neurotransmission. In addition, these opioid and
      nonopioid modes of action appear to act synergistically. Tramadol has been shown
      to provide effective analgesia after both intramuscular and intravenous
      administration for the treatment of postoperative pain. The drug is available in
      formulations suitable for oral, rectal and parenteral administration. Clinically
      effective analgesic doses of tramadol were comparable to those of pethidine
      (meperidine) and about 10 times higher than those of morphine. 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. A randomised double-blind study reported acceptable analgesia with
      postoperative intravenous tramadol 50mg, repeated once if required after 30
      minutes. It produced an effect similar to that of morphine 5mg or the alpha 2
      agonist, clonidine 150 micrograms. In another study, it was shown that the 50mg
      dose of tramadol fulfilled the requirements of an analgesic for the treatment of
      moderate postoperative pain, whereas for severe pain a higher dose was
      recommended. Tramadol is generally well tolerated, the most common adverse events
      being nausea and vomiting. In contrast to agents such as morphine and pethidine,
      clinically relevant respiratory depression is rarely observed during tramadol
      administration at equipotent doses and consequently it can be recommended for
      first-line management of postoperative pain instead of morphine. It is also
      associated with a low incidence of cardiac depression and significantly less
      dizziness and drowsiness than morphine. Finally, the dependence and abuse
      potential with tramadol is negligible. Comparative studies have generally shown
      that tramadol is more effective than NSAIDs for controlling post operative pain.
      Use of a combination of tramadol and NSAIDs allows the tramadol dose to be
      reduced and results in a lower incidence of adverse effects. Patient controlled
      analgesia (PCA) with tramadol has been frequently used and is well accepted by
      patients. Wide individual variations exist with regard to analgesic requirements
      and, nowadays, it is generally accepted that adequate pain management implies
      systematic individualisation of the therapy, i.e. titration of the analgesic
      effect to individual needs. Demand and loading doses play a decisive role in the
      success of PCA. Analgesic failures requiring rescue medication are rare, but it
      should be stressed that these can always occur with weak opioids. In conclusion,
      tramadol can be recommended as a basic analgesic for the treatment of moderate to
      severe pain. In the event of analgesic failure with tramadol, there is no reason
      not to switch to more potent opioids. Although no studies are available regarding
      its use in the management of postoperative pain after day case surgery, tramadol
      is frequently administered with good results in such patients. The most important
      side effects of tramadol are nausea and emesis, which can often be prevented by
      slow injection and administration of a prophylactic antiemetic such as
      metoclopramid

PMID- 9190323
TI  - [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot
      study versus clomipramine with or without levomepromazine].
AB  - To date, no universally applicable recommendations are available for the
      treatment of patients with postherpetic neuralgia. A mixture of clinical
      anecdotes, experimental findings and observations from clinical trials form the
      basis of the medical arsenal for this condition. Tricyclic antidepressants are
      commonly used, and clinical experience and several investigations have documented
      their effectiveness. Today, single entity antidepressants, which can be combined
      with neuroleptics to increase analgesia, are generally recommended for the
      treatment of postherpetic neuralgia. Some authors also recommend the additional
      administration of an opioid if analgesia is inadequate. Just over a decade ago,
      opioids were considered ineffective for the treatment of neuropathic pain;
      however, more recent investigations relating to the use of opioids, primarily in
      the treatment of nontumour-related chronic pain, have led to a revision of their
      use in neuropathic pain. Nevertheless, the use of opioid therapy for neurogenic
      pain remains controversial. Tramadol is a synthetic, centrally acting analgesic
      with both opioid and nonopioid analgesic activity. The nonopioid component is
      related to the inhibition of noradrenaline (norepinephrine) reuptake and
      stimulation of serotonin (5-hydroxytryptamine; 5-HT) release at the spinal level.
      In this regard, there are parallels with antidepressants, which are believed to
      potentiate the effect of biogenic amines in endogenous pain-relieving systems.
      There is evidence that, in tramadol, both mechanisms act synergistically with
      respect to analgesia. The aim of this pilot study was to investigate, for the
      first time, the analgesic efficacy and tolerability of tramadol, compared with
      the antidepressant clomipramine, in the treatment of postherpetic neuralgia. If
      necessary, clomipramine was used in combination with the neuroleptic
      levomepromazine. The study allowed individualised dosages at predetermined
      intervals up to a maximum daily dose of tramadol 600mg and clomipramine 100mg, or
      clomipramine 100mg with or without levomepromazine 100mg. 21 (60%) of 35
      randomised patients (> or = 65 years) received the study medication over the 6
      week period [tramadol n = 10; clomipramine with or without levomepromazine) n =
      11]. After 3 weeks' treatment the dosage in both groups remained almost constant
      for the rest of the 6-week treatment phase (mean daily dose: tramadol 250 to
      290mg; clomipramine 59.1 to 63.6mg). Only 3 patients required the combination of
      clomipramine and levomepromazine. At the outset, both groups recorded an average
      pain level of 'moderate' to 'very severe'. In correlation with increasing the
      study medication, this had decreased to 'slight' by the end of the treatment,
      when 9 of 10 patients in the tramadol group and of 6 of 11 patients in the
      clomipramine group retrospectively rated their analgesia as excellent, good or
      satisfactory. The psychological/physical condition of the patients did not change
      significantly during tramadol treatment. Sensitivity and depression parameters
      decreased in the clomipramine group. The incidence of adverse events for all
      patients was similar in both groups (tramadol 76.5%; clomipramine with or without
      levomepromazine 83.3%). In conclusion, tramadol would appear to be an interesting
      therapeutic alternative for pain relief in postherpetic neuralgia, particularly
      in patients who are not depressed. In clinical practice, tramadol and
      clomipramine can best be used differentially. For example, tramadol could be the
      drug of first choice in patients with obvious cardiovascular disease (not an
      uncommon problem in the > or = 65 year age group) in whom antidepressants are
      contraindicated, and similarly in patients in whom an antidepressant effect is
      not required. (ABSTRACT TRUNCATED)

PMID- 9190324
TI  - [Effectiveness and tolerance of tramadol in cancer pain. A comparative study with
      respect to buprenorphine].
AB  - Opioid analgesics represent one of the most important tools in a sequential
      pharmacological approach to oncological pain relief. They are recommended by the
      WHO when nonsteroidal anti-inflammatory drugs (NSAIDs) no longer provide adequate
      analgesia. However, the use of opioids is limited because of their numerous and
      often severe adverse effects. This aspect of opioids has motivated continuous
      research projects aimed at discovering drugs that can provide maximum pain relief
      but with improved tolerability. Tramadol is a new, centrally acting analgesic
      with a dual mechanism of action. It shows a selective interaction with mu
      receptors, which are responsible for nociception, and has weak pharmacodynamic
      activity on other opioid receptors. At the same time, it acts synergistically on
      neuroamine transmission by inhibiting synaptic noradrenaline (norepinephrine)
      reuptake and inducing intrasynaptic serotonin (5-hydroxytryptamine; 5-HT)
      release. From a pharmacokinetic standpoint, tramadol offers high bioavailability,
      with similar patterns after oral or parenteral administration (half-life 5 to 7
      hours, time to peak plasma concentration 3.1 hours, and approximately 20% plasma
      protein binding). Although the efficacy of tramadol is comparable to that of
      other drugs with similar modes of action, the incidence of side effects such as
      constipation and respiratory depression is lower. The frequency of euphoria and
      dysphoria is negligible, resulting in little risk of abuse or dependence. It
      therefore seemed appropriate to further investigate the efficacy and tolerability
      of tramadol, defined as having only weak potency, in comparison with a widely
      used opioid, in oncological pain. Buprenorphine was selected as an opioid with a
      potency equivalent to half that of morphine, but with tolerability that is
      partially limited by the fact that it frequently gives rise to adverse reactions
      considered typical of stronger opioids. To compare the analgesic effect and
      tolerability of tramadol and buprenorphine, 60 patients (44 men, 16 women;
      average age 61.4 years), all presenting with advanced tumours, were treated
      orally in a controlled crossover trial with randomised sequences. Patients took
      both drugs, each for a week, with a 24-hour washout period between treatments.
      Tramadol was prescribed at the daily dose of 300mg, orally, and buprenorphine at
      0.6 mg/day, as a sublingual preparation. Assessments were made of Karnofsky
      performance status and severity of pain before and during the 4 hours after
      taking the 2 drugs. Each patient also completed a daily diary recording the
      severity of pain 1 hour after the dose, the evolution of pain during the day and
      its severity compared with that on the previous day. They also assessed the
      duration and quality of sleep. The Karnofsky index changed little with either
      treatment, but all other variables showed worthwhile improvement, indicating the
      significant analgesic effect of both drugs. Buprenorphine and tramadol had a
      similar analgesic effect, although the improvement with the test drug was
      significant within 1 hour of administration (p < 0.05 compared with baseline) and
      more marked (p < 0.05 on day 2 compared with buprenorpine). At the end of
      tramadol treatment, sleep had also improved, both quantitatively and
      qualitatively (both p < 0.05). The final assessment was significantly in favour
      of tramadol as regards efficacy (p < 0.05) and patient acceptability (p < 0.01).
      Thus, tramadol was better tolerated than buprenorphine, and caused fewer and
      milder adverse reactions. Only 1 patient discontinued tramadol, compared with 18
      using reference therapy. Tramadol, although theoretically less potent,
      nevertheless brought about as much pain relief as the comparator opioid. In
      conclusion, for this class of drug, tramadol provides an excellent balance
      between efficacy and tolerability, confirming preliminary studies.

PMID- 9190325
TI  - [Tolerance and safety of tramadol use. Results of international studies and data
      from drug surveillance].
AB  - This article presents a summary of drug safety data concerning the use of
      tramadol hydrochloride and an outline of the specific aspects of this analgesic
      in particular with regard to respiratory depression and dependence potential.
      Information from phase II to IV clinical studies, postmarketing surveillance
      studies (covering safety data from a total of more than 21,000 patients) and the
      spontaneous reporting system have been taken into consideration. The data from
      the spontaneous reporting system covers the period between 1977 and 1993, during
      which more than one billion single dose units were distributed throughout the
      world. The phase II to IV studies compare acute intravenous, acute intramuscular,
      acute oral and multiple dose oral administration Postmarketing surveillance
      studies provide a picture of everyday use of tramadol in general medical
      practice. Further analyses were performed to provide information about the gender
      , age- and dose-related distribution of adverse reactions The prevalence of side
      effects was calculated by comparing the number of symptoms with the number of
      patients. The pooled data from the clinical studies and the postmarketing
      surveillance studies reveal that the most commonly observed side effects were
      nausea, dizziness, drowsiness, tiredness, sweating, vomiting and dry mouth, with
      an overall incidence of between 1 and 6%. In the postmarketing surveillance
      studies on long term and acute administration, the profile of adverse events was
      qualitatively almost identical to that in the phase II to IV studies. However,
      there were distinct quantitative differences it favour of the long term studies.
      In the postmarketing surveillance study on acute parenteral administration, the
      incidences of nausea and vomiting were only 4.2 and 0.5% respectively, which is
      significantly lower than the 20.7 and 11.4% in the patient-controlled analgesia
      studies. Nevertheless, it is important to take into consideration the different
      conditions in these studies. All the postmarketing surveillance studies were
      outpatient studies, whereas almost all of the phase II to IV studies were carried
      out in hospitals. The studies with intravenous and intramuscular administration
      were mainly postoperative, which explains the relatively high incidence of nausea
      and vomiting, 17.8 and 7.0%, respectively, with intramuscular administration. The
      different conditions in the phase II to IV studies and the postmarketing
      surveillance studies are also reflected in the occurrence of dizziness and
      postural hypotension: The incidence of dizziness in the postmarketing
      surveillance studies is slightly higher than that observed in the phase II to IV
      studies. Particularly in the studies with intravenous and intramuscular
      administration, the patients were confined to bed and were therefore much less
      sensitive to dizziness than those in the long term oral and postmarketing
      surveillance studies, who were all outpatients. On the other hand, postural
      hypotension played almost no role in the multiple dose studies, in which the oral
      formulation were used most frequently. It is interesting to note that diarrhoea,
      pruritus and gastrointestinal disorder (except nausea and vomiting) are mainly
      reported in the multiple dose studies in the groups receiving oral tramadol, and
      also in the postmarketing surveillance studies. Once again, the study conditions
      may well be the explanation. The adverse effects reported in both clinical and
      postmarketing surveillance studies are similar to those in the spontaneous
      reports. The most frequently documented adverse effects in clinical and
      postmarketing surveillance studies, i.e. nausea/vomiting, dizziness, drowsiness,
      tiredness, sweating and dry mouth, are noted very infrequently in spontaneous
      reports, since in medical practice these side effects are usually known and are
      described in the product information. Almost all reports referring to
      abuse/dependence are connected with pain therapy; they give no reason to suspect
      any pro

PMID- 9190326
TI  - [The bioindication of mutagens in the soil of rural districts].
AB  - The cumulative mutagenic activity (CMA) of soil pollution was investigated in
      rural areas. The use of pesticides in agricultural practice increased soil
      mutagen levels. There was also higher mutagenic pollution for soil along the road
      with heavy traffic.

PMID- 9190327
TI  - [The terminology in assessing the recovery of human work capacity].
AB  - The paper deals with the scientific and practical expediency of using the unified
      terminology in the rehabilitation of working capacity in man. The term
      "recreation" is proposed to define the processes and phenomena associated with
      recovered functions and forces of the human body, which have been lost at work.

PMID- 9190328
TI  - [The work conditions and health status of women working in the gas-processing
      industry].

PMID- 9190329
TI  - [The importance of collagen in the biological value of meat].
AB  - Rat experiments showed that increases in the levels of collagen from 6.1 to 15.5%
      of the total content of meat proteins enhanced the growth and weight indices of
      animals. The differences in the biological value of the above quantity of
      collagen for man and rats were attributable to different physiological
      requirements for the quality of protein. Therefore, the findings in man are in
      agreement with those in rats.

PMID- 9190330
TI  - [Problems in the hygienic rationalization of the therapeutic and prophylactic
      nutrition of industrial workers].
AB  - Based on generalization and analysis of instructions and guidelines for
      therapeutical and prophylactic diets of workers, ways of its optimization were
      proposed, by using bifide-containing acid dairy products as a preventive agent
      against possible occupational diseases caused by occupational factors.

PMID- 9190331
TI  - [The health status of children in the new type of educational institutions].
AB  - The impact of a teaching process on the working capacity of schoolchildren at new
      type educational establishments (lycees, colleges), as well as at general
      educational schools was studied. There was a correlation between the pupils'
      health status and immunity and the level of educational workload, the air
      environment of institutional rooms, regimens.

PMID- 9190332
TI  - [The assessment of the mental health of children with psychosomatic diseases].
AB  - The mental health of children and adolescents who suffered from gastrointestinal
      diseases due to psychosomatic causes (duodenal ulcer, chronic gastroduodenitis)
      was examined. Those with the diseases are a group at risk for nervous and mental
      disorders, and impaired psychophysical adaptation.

PMID- 9190333
TI  - [The dynamic physical development of schoolchildren in Nizhni Novgorod].
AB  - In the past 55 years, the trends in the physical development of school children
      of a large industrial city have been in agreement with the global ones in the
      growth and development of children and adolescents. In the past decade, there
      have been unfavourable tendencies in the physical development of schoolchildren.
      The physical development of children is an indicator of the social and economic
      status, living conditions, and the environment. Follow-ups should be an
      obligatory element of monitoring the population's health.

PMID- 9190334
TI  - [The validation of a system of indices for social hygiene monitoring at the local
      level].

PMID- 9190335
TI  - [The relationship of cancer morbidity to air pollution].

PMID- 9190336
TI  - [The characteristics of external respiratory function in students].

PMID- 9190337
TI  - [The need to development a new concept in the study of habitat factors].

PMID- 9190338
TI  - [The effect of sodium nitrite on the functions of the gastrointestinal tract].

PMID- 9190339
TI  - [The effect of polymeric materials on the animal organism in ontogeny].

PMID- 9190340
TI  - [The effect of the noise factor on patients with cardiovascular diseases at a
      sanatorium].

PMID- 9190341
TI  - [The dynamics of environmental factors, morbidity and demographic indices in
      Zaporozhye].

PMID- 9190342
TI  - [A sanitary chemical evaluation of polyether urethane endoprostheses].

PMID- 9190343
TI  - [Harmful habits and the morbidity of the population of Pomorze Zachodnie,
      Poland].

PMID- 9190344
TI  - [The role of hygiene departments in the system for training health officers].

PMID- 9190345
TI  - [Methodological aspects in the study and assessment of the health status of the
      population].

PMID- 9190346
TI  - [The estimation of the real hazards of chemical substances based on an analysis
      of the concentration (dose)-body status relationship].

PMID- 9190347
TI  - [The validation of the maximum permissible concentration of pyromellitic
      dianhydride in the atmosphere].
AB  - The maximum allowable concentration (MAC) of pyromellitic acid dianhydride (PMAD)
      in the ambient air was substabtiated by physiological, hematological, and
      physiological methods. The inhalation of this substance by animals reduced their
      body weight, erythrocytic osmotic resistance, enhanced animals' sensitization.
      The mean daily MAC of PMAD was found to be 0.01 mg/m3. PMAD was considered to be
      Hazard Class 2.

PMID- 9190348
TI  - [The spectrophotometric determination of naphthylmaleimide and pyridylmaleimide].

PMID- 9190349
TI  - [A theoretical analysis of paired empirical relationships of the type
      concentration-time and structure-activity from the viewpoint of biokinetics].

PMID- 9190350
TI  - [The hygienic evaluation of a local unit for sewage treatment].
AB  - A complex of hygienic criteria was proposed to assess a Bioclere local unit for
      sewage treatment. These included: the effects of the organoleptic properties of
      sewage, better sanitary and chemical parameters, lower levels of inorganic and
      organic chemicals, surfactants, microbiological parameters, stability of
      treatment regimens. The Bioclere unit has some advantages over the similar ones
      and may be useful when an object cannot be connected to the sewage network.

PMID- 9190351
TI  - [Manual intrauterine aspiration in the treatment of incomplete abortion].
AB  - Manual vacuum aspiration (MVA) is a method proposed for uterine evacuation in
      cases of incomplete abortion, using a syringe of plastic material to produce
      negative pressure. With this technique, we treated 122 cases of different types
      of abortion at The Instituto Nacional de Perinatologia, and results obtained were
      compared with those of 126 women treated with standard dilation and curettage
      (D&C). The sociodemographic characteristics of the two groups were similar. Molar
      pregnancy and blind ova were more frequent in cases treated with MVA. Types of
      anesthesia used were similar in both groups with the exception of 10 cases of
      MVA, that received paracervical block. Four surgical complications occurred, one
      of hemorrhage in each group and two cases of incomplete evacuation in the MVA
      group. Histopathological examinations using morphometric techniques showed
      similar proportions, of fetal parts, villi, decidua, myometrial cells and blood
      clots for both groups. It was concluded that MVA is as effective and safe as D&C,
      it is easy to perform, and is not associated with important complications. It can
      be used as an advantageous option for the evacuation of molar pregnancy.

PMID- 9190352
TI  - [Attitude to and acceptance of prenatal cytogenetic diagnosis by pregnant women].
AB  - Methods for cytogenetic prenatal diagnosis available in Mexico require from women
      to accept the risk of procedures and to take a decision in the case of an
      abnormal result. We applied a questionnaire to 264 pregnant women from August
      1990 to July 1991 with the purpose of describing the characteristics of these
      women and the factors involved in making the decision. Two hundred and nine
      patients (79%) accepted the procedures. The acceptance was related with a high
      level of studies and inversely related to their religious beliefs. The
      interviewer did not influence the decision; but it was important to have previous
      information about the procedures. Those women with the highest social, financial,
      and study level and those who did not practice their religion accepted the
      possibility of an abortion.

PMID- 9190354
TI  - [Caudal appendix in sequential defects of amniotic rupture. A case report].
AB  - We present the case of a stillbirth, who presented with constrictive amniotic
      bands, amniotic adhesions, limb-body-wall complex, and the presence of a
      pseudotail that was studied at the Pathology Unit of the Acapulco General
      Hospital. This entity, formerly termed cyllosomus and pleurosomus, is rare. The
      anomalies were interpreted as being band- and/or compression-related defects. The
      latter included limb deficiency, body wall deficiency, neural tube defects,
      scoliosis, postural deformations, growth deficiency and short umbilical cord. The
      scanty literature on this subject in Mexico is due to the lack of interest to
      report isolated cases like the one we comment here, which depends on local
      interest in teratology.

PMID- 9190353
TI  - [Determination by ultrasound of chorionicity in twin pregnancy].
AB  - Twins, specially those of monochorionic and monoamniotic pregnancies, are exposed
      to many perinatal risks and complications. The objective of this study was to
      evaluate the usefulness of ultrasonographic determination of the chorionicity of
      human placental by counting the number of layers in amniotic membranes. Thirty
      eight patients with twin pregnancies were studied prospectively. The
      ultrasonographic evaluation of membranes layers was made only once, between the
      weeks and 16 and 30 of pregnancy. When two layers were identified, the
      placentation was determined as monochorionic, and when four layers were seen, the
      diagnosis of bichorionic placentation was made. The type of chorionicity was
      confirmed by histologic study of the placenta. With ultrasound, the chorionicity
      was correctly determined in 36 out of 38 cases, for a total predictive value of
      94.6%. The capacity for diagnosing bichorionic (4 layers) placentation was 100%
      (22/22) and 87.6% (14/16) for monochorionic (2 layers) placentation. The
      ultrasonographic evaluation of the amniotic membranes number is an efficient
      method to recognize the chorionicity of placenta and constitutes an useful and
      simple method giving important information in perinatal prognosis.

PMID- 9190355
TI  - [Obstetric hysterectomy. Review of 675 cases at the Instituto Nacional de
      Perinatologia].
AB  - A retrospective study of 675 patients subject to obstetric hysterectomy from
      January 1st, 1985 to December 31st, 1995 at the Instituto Nacional de
      Perinatologia was carried out. The incidence of this procedure reached its
      highest level in patients from 26 to 40 years, which represented 60.5% (409
      cases) of the studied population. Patients with one previous cesarean section
      comprised 34.8% of total obstetric hysterectomies, followed by women with two to
      three previous cesarean sections (24.5% and 22.2%, respectively). As for
      gestational age, it reached term in 51.1% (345 cases), pre-term in 38% (257),
      post-term in 1.4% (10), and less than 20 weeks in 9.3% (63 cases). Main
      indications for obstetric hysterectomy included placenta accreta in 34.07% (230
      cases), uterine atony in 32.4% (219), deciduomyometritis in 6.3% (43 cases), and
      uterine rupture in 4.5% (31). Most frequent complications included hypovolemia
      (12.1%), bladder injury (5.4%), and ureteral injury (0.7%). Postoperative
      complications included anemia (61.6%), febrile syndrome (7.5%), mechanic ileum
      (7.5%), wall abscess (3.4%), and vesicovaginal fistula (1.6%). A total of eight
      maternal deaths (1.1%) was reported.

PMID- 9190356
TI  - [Immunological aspects of endometriosis].
AB  - The effect of adherence process on Fallopian tubes and ovaries in late stages
      endometriosis is clear, but it is more important to understand pathophysiologic
      mechanism of infertility in minimal, mild endometriosis. Although the etiology of
      endometriosis is unknown, components of the immune system may be involved and
      play a central role in the pathogenesis of the disease by immunologically
      altering the peritoneal microenvironment. Increased number and activity of
      leucocyte subpopulations in the peritoneal fluid result in cytotoxic effects that
      exert adverse influence on spermatozoa, oocyte, germ cell interaction, and early
      embryo development, while cytokine and growth factor secretion stimulates or
      promotes cellular proliferation of endometriotic tissue in an "immunological
      tolerance" environment. The immunological aspects of endometriosis, including
      autocrine or paracrine pathways of intercellular communication, are reviewed.

PMID- 9190357
TI  - [Usefulness of fresh wet mount examination in the diagnosis of vaginal
      candidiasis].
AB  - A prospective study was done at the Clinic for Sexually Transmitted Diseases of
      the Department of Infectology, Instituto Nacional de Perinatologia, Mexico City,
      in order to validate the fresh wet mount examination as a confirmatory test for
      vaginal candidiasis. Ninety six patients with cervico-vaginal infection were
      included, 22 of them had clinical candidiasis (22.9%). The fresh wet mount
      examination showed the presence of yeast and/or pseudomycelium in all 2 samples
      (100%). The presence of Candida in the cultures was confirmed in 18 of the 22
      specimens (81.8). Negative in 71/96 (73.9%) (Three cultures were not processed).
      The fresh wet mount examination had a sensitivity of 100% and a specificity of
      94.8%. The positive predictive value was 88.8% while the negative predictive
      value was 100%. It can be concluded that the fresh wet mount examination is very
      recommendable, useful, economic and easy to practice at the physician's office
      for the confirmation of vaginal candidiasis.

PMID- 9190358
TI  - [Breast tuberculosis, A case report and a review of the literature].
AB  - Breast tuberculosis is considered a rare entity throughout the world. A case of
      tuberculous mastitis in a 39 year woman who presented with a breast mass with
      initial diagnosis of carcinoma is described. A review of literature was also
      done.

PMID- 9190359
TI  - [Apparent heterogeneous distribution of progesterone receptors in certain cases
      of endometrial carcinoma].
AB  - The progesterone receptor contents in the cytosol of two of three samples of same
      tumor was measured in 19 cases of endometrial cancer. The receptor concentration
      in one sample of each tumor was calculated by Scatchard analysis of specific
      binding data; in the other, one or two samples of each tumor, the receptor
      concentration was calculated by using a single point. All tumors did have
      receptors at least in one of the two or three samples. Ten tumors showed certain
      consistency in the receptor content in the two or three samples. On the other
      hand, a striking variability in the receptor content between the two or three
      samples of each of the remaining tumors was found, ranging from zero to several
      hundred femtomoles/mg of protein. In seven cases, follow-up was possible during
      66 months, and the response to progestagen treatment was independent from the
      progesterone-receptor content. Our results suggest that the analysis of a single
      site of a tumor would reveal values that might not be representative of the tumor
      and, furthermore, it would explain, at least partially, the uncertain response to
      progestagen therapy that has been frequently described.

PMID- 9190361
TI  - Special issue in memoriam of Albert Valek.

PMID- 9190360
TI  - Heterogeneity of gonadoblastoma germ cells: similarities with immature germ
      cells, spermatogonia and testicular carcinoma in situ cells.
AB  - Gonadoblastoma is defined as a neoplasm containing nests of germ cells and cells
      resembling Sertoli cells or granulosa cells. Gonadoblastomas arise almost
      exclusively in dysgenetic gonads. They are associated with an increased risk of
      developing germ cell tumours. Testicular germ cell tumours in adults are preceded
      by carcinoma in situ cells, which are characterized by their morphology, by their
      immunohistochemical expression of placental-like alkaline phosphatase, the proto
      oncogene c-kit and/or epitopes for the monoclonal antibodies M2A, 43-9F and TRA-1
      60, and by their aneuploid DNA content. In order to elucidate if gonadoblastomas
      are in situ neoplasms from the beginning, showing similarities with carcinoma in
      situ cells in otherwise normal testes, we investigated the germ cells in
      gonadoblastomas for their expression of the immunohistochemical markers of
      carcinoma in situ cells from six patients aged 8 1/2 months to 20 years and 4
      months. In addition, the DNA content of the germ cells from five of the six
      patients was also determined by densitometric measurement on Feulgen stained
      specimens. The germ cell populations were heterogeneous both within the same
      patient and between the patients. Expression of the testicular carcinoma in situ
      markers was detected in specimens from all the patients and germ cells with an
      aneuploid DNA distribution pattern in accordance with testicular carcinoma in
      situ cells were detected. However, apparently normal immature germ cells were
      also present in four of the patients of whom two also had germ cells with a
      morphology similar to normal spermatogonia. Thus, gonadoblastoma is most likely
      an in situ germ cell neoplasia from the beginning. It seems probable that the
      germ cell tumours associated with gonadoblastomas originate from the carcinoma in
      situ cells inside the gonadoblastoma. Our findings of carcinoma in situ cells in
      gonadoblastomas from children support the theory that the cells arose prenatally.

PMID- 9190363
TI  - [Determination of the facial morphology and its reconstruction].

PMID- 9190362
TI  - Protein kinase A anchoring.

PMID- 9190364
TI  - [Study on intentional replantation in rats--comparison between germ-free rats and
      those raised in a normal environment].

PMID- 9190365
TI  - [Development of a new method to detect bacterial receptors by using TLC blotting
      and its application to the causative agents of oral infections].

PMID- 9190366
TI  - [Highly elastic wire made of a Co-Ni-Cr-Mo alloy for orthodontic use].

PMID- 9190367
TI  - [Analysis of gene Fringe related to neurogenesis using chick embryo].

PMID- 9190368
TI  - [Pericranial sinus].
AB  - This study concerns four cases of sinus pericranii observed at the Neurological
      Department of Nancy. Sinus pericranii is a direct communication between the outer
      surface of the skull and the intracranial venous sinuses. It may be congenital,
      acquired or traumatic. This abnormality, usually located in the midline and often
      in the frontal region, is usually symptomless, but some patients complain of
      headache, nausea and vertigo. Sinus pericranii shows as a fluctuating non
      pulsatile mass of reddish or bluish colour, expanding when the patient bends his
      head down. Radiography usually shows one or several bone defects opposite the
      lesion found at CT bone window. On soft tissue window the mass is not calcified
      and usually enhanced by contrast injection. It is sometimes possible to visualize
      the vascular communication between the extracranial region and the underlying
      dural sinus. When visualization is blurred, or CT shows intracerebral
      abnormalities, MRI examination is required. Angiography with subtraction in
      venous phase (40 to 60 seconds after the injection), sometimes aided by films
      taken in head down position. It is of interest only in cases where CT and MRI
      have shown associated vascular abnormalities. Otherwise, direct injection of
      contrast medium into the malformation makes it possible to assert the diagnosis
      of sinus pericranii and to determine the flow rate within the malformation, which
      to some extent commands the the therapeutic technique. In patients with small and
      asymptomatic sinus pericranii absention is the rule. When the sinus is of
      moderate size, and the flow rate not rapid and when there is no significant
      communication with the cerebral veins, endovascular sclerosis may be advocated.
      In all other cases, surgical removal is recommended and is usually easy.

PMID- 9190369
TI  - [Reformatting 3-dimensional medical images. Application to MRI and scanners].
AB  - Several kinds of images, each giving a different information, are now available
      to radiologists. The MRI images have excellent contrast resolution and enable
      soft tissues to be differentiated, but they do not distinguish structures with
      low water content, notably air and bone, whereas these are easily recognized by
      CT. The aim of this study is to present a simple, entirely radiologist-supervised
      method to examine the radiological data of any patient, obtained from several
      kinds of images. MRI is performed using a GEMS Signa, 1.5 Tesla, 4.9 version
      magnet. Acquisitions are T1- or T2-weighted spin-echo or gradient sequences, with
      a 256 or 512 matrix, on axial sections, with of without contrast injection. CT is
      performed using a GEMS Hi Speed scanner. Acquisitions are obtained on a 512
      matrix and with a "Soft" or "Bone" filter, without contrast injection. The two
      series of sections are transmitted, through an Etherne network, to a Sun console
      where the two corresponding volumes are reconstructed on a GEMS Voxtol by means
      of a 3-dimensional soft ware for image treatment. At least 3 couples define the
      rotation and translation required for one of the two volumes to reset it in the
      guide mark of the other. The soft ware then looks for the best transformation, in
      terms of least square, between the two 3-dimensional volumes. The calculation
      demands only a few seconds. One of the two objects is then recalculated in the
      guide mark of the other. The cursor positioned by the user on any point of the
      object is linked to a second cursor which will automatically position itself on
      the corresponding point of the other object. The accuracy obtained (about one
      millimeter) is specified by the soft ware which indicates how to improve
      resetting. In addition to its teaching value, this superimposition image can help
      in the diagnosis and can be used for surgical stimulation because it is possible
      to mix the images. This mixing gives access to a new type of imaging, since the
      images spared can be reconstructed in volume, and treated in all planes, as a CT
      or MRI examination. The term "Anatomical Reconstruction Images" may be suggested
      for this new type of examination. Beside intermodal comparison, one may also
      imagine that the soft ware can be used to follow up the patient over time (repeat
      MRI) or to make comparisons between several objects, although the elastic
      resetting method is more often appropriate in the second case.

PMID- 9190370
TI  - [Cerebral lesions following convulsive partial status epilepticus. Clinical,
      neuroradiologic and PET study of a case].
AB  - An 11-year-old girl developed signs of intracranial hypertension after status
      epilepticus with convulsive movements of her right upper limb. Computerized
      tomography revealed left hemispheric hypodensity with mass effect, attributed to
      vasogenic edema. Intracranial hypertension was controlled under intracranial
      pressure monitoring and clinical status slowly improved. The patient was aphasic
      and right hemiplegic when she recovered consciousness but she remarkably
      recovered from her neurological deficits during the following two years despite
      neuroradiological evolution demonstrating extensive destruction of the left
      cortex and white matter. Two positron emission tomography (PET) scans were
      performed respectively six weeks and eight months after status epilepticus, and
      both demonstrated profound left hemispheric hypometabolism except in the
      lenticular nucleus and a restricted area of motor/premotor cortex. On the other
      hand, glucose metabolism in the right hemisphere was heterogeneously increased on
      the second PET when compared with the first PET. We concluded that, in this case,
      clinical recovery might have implicated functional reorganization arising from
      the intact hemisphere.

PMID- 9190371
TI  - [Computed tomographic aspects of secondary cholesteatomas of the middle ear and
      petrous bone].
AB  - The authors present their experience of secondary cholesteatomas of the middle
      ear explored by computerized tomography (CT). Following a brief
      anatomicopathological description of secondary petrous bone cholesteatomas, and
      of the CT technique used for their exploration, they describe and illustrate the
      classical "bag-shaped" internal or external attical forms usually extended to the
      antrum and the mastoid process, and the less common locations often due to
      relapse or postoperative recurrences (anterior hypotympanic or posterior
      mastoidal). The holotympanic forms, usually due to "lamellar" cholesteatomas,
      create diagnostic problems with other opacities in the cavity, as also do certain
      forms that are evacuated spontaneously or by aspiration. One of the qualities of
      CT lies in the preoperative extension assessment. The lesion may extend towards
      the internal wall of the cavity (lateral semicircular canal, second portion of
      the facial nerve), towards the labyrinth to the petrosal apex and/or the
      geniculate ganglion, and above all towards the inferior labyrinth which might
      bring the cholesteatoma into contact with large vessels (e.g. jugular vein bulb
      for postero-inferior extensions, carotid canal for antero-inferior extensions).
      Extension into anfractuosities of the cavity walls (sinus tympani, subratubal
      fossette) must be systematically looked for in order to avoid postoperative
      recurrences.

PMID- 9190372
TI  - [The value of magnetic resonance imaging in the diagnosis of spinal cord
      hemangioblastoma. Apropos of 12 cases].
AB  - This study concerned a series of 12 patients, 4 of whom had Von Hippel-Lindau
      disease. Six of these patients were explored by myelography, 6 by spinal cord
      angiography, 8 by CT scan with contrast injection and 12 by MRI, with gadolinium
      injection in 8. MRI proved to be the choice examination for the diagnosis of
      spinal cord tumor, but gadolinium injection was necessary since it made it
      possible to detect the tumoral bud and its intense enhancement. The absence of
      gadolinium injection led us to an erroneous initial diagnosis of syringomyelia in
      two patients and glioma in one. Sagittal sections made it easier to evaluate the
      tumoral extension in patients with evidence or suspicion of Von Hippel-Lindau
      disease. Arteriography was indicated, as it provided a preoperative map and
      diagnosed punctiform lesions.

PMID- 9190374
TI  - [Torticollis and C1-C2 rotation subluxation. Apropos of a case. The value of a
      dynamic scanner and of a 3-dimensional scanner].
AB  - The authors report the rare and complex case of a girl who had been followed
      since the age of 3 years for hydrocephalus the cause of which was found only when
      she was 6-year old. The causative agent was a pilocytic astrocytoma of the
      cerebellum. On April 10, 1990, she underwent subtotal excision of the tumour,
      associated with radiotherapy. Four months later she developed an increasingly
      painful and irreducible torticollis which did not respond to tractions. Dynamic
      CT scans and 3-dimensional CT scans were performed in the fourth month and
      provided a diagnosis of right C1-C2 rotatory subluxation. There was no history of
      injury and no sign of inflammatory process. Rotatory subluxation is a very rare
      lesion difficult to diagnose, and few cases have been published, although the
      signs are those of classical torticollis in children. When medical treatment
      fails, often due to belated diagnosis, the only surgical treatment is uni- or
      bilateral C1-C2 arthrodesis. If the diagnosis can be made at an early stage,
      reduction of the rotatory luxation is usually easy and without consequences to
      the child. It is therefore recommended to perform a dynamic CT scan and a 3D CT
      scan as soon as possible in all children with lasting painful torticollis.

PMID- 9190375
TI  - Lucien Appel prize for neuroradiology 1994.

PMID- 9190373
TI  - [Complications of the intravascular treatment of intracranial aneurysms using
      metal microcoils. Embolization using coils in intracranial aneurysms].
AB  - Embolization of intracranial aneurysms with coils. The authors present the
      results and complications of microcoils embolization of intracranial aneurysms in
      28 patients. Fibers platinum microcoils were used (Target Therapeutic) 28
      patients (males: 6, females: 22; mean age: 51 years) were treated, 27 suffered
      from sub-arachnoid hemorrhage (SAH) and one presented with a pseudotumoral
      syndrome (giant aneurysm). All patients were evaluated on the day of treatment,
      according to the World Federation of Neuro-Surgeon classification (W.F.N.S.) of
      SAH and after 4 months of follow-up. At a mean follow-up period of 4 months,
      according to Glasgow Outcome Scale (G.O.S.) there were 13 cases of good results,
      5 cases of "moderate disability", 2 cases of "severe disability", 2 cases of
      "vegetative state" and 6 deaths. Complications were observed in 11/28 cases.
      Coils migration and malposition in the parent artery were linked to the procedure
      (mechanical detachable coil) and resulted in severe deficit (one case), transient
      disability (one case) or went unnoticed (4 cases). Primary or secondary complete
      occlusion was achieved in 8/28 patients (32%). A majority of cases (11 cases)
      ended with stable residual aneurysmal sac lumen while rebleeding occurred in 3
      patients and was responsible for 2 deaths. In the third case a favourable outcome
      was obtained after balloon occlusion of the parent artery.

PMID- 9190376
TI  - [Imaging diagnosis and functional tests--paranasal sinus cyst].

PMID- 9190377
TI  - [New trial of medical education at Fukushima Prefecture Medical School during
      last 3 years--seminar by the student for education of neurophysiology].

PMID- 9190378
TI  - Cloning of the cDNA encoding a neuronal myosin heavy chain from mammalian brain
      and its differential expression within the central nervous system.

PMID- 9190379
TI  - IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Human
      Immunodeficiency Viruses and Human T-Cell Lymphotropic Viruses. Lyon, France, 1
      18 June 1996.

PMID- 9190380
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 1. Current status and problems related to setting
      reference criteria (normal].

PMID- 9190381
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 10. The results of the analysis conducted to set
      reference ranges for 13].

PMID- 9190383
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 4. An IFCC international reference for plasma
      protein (CRM 470/RPPHS)--its].

PMID- 9190382
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 11. A practical list of reference intervals for
      13 items of serum proteins].

PMID- 9190384
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 5. A system for the analysis of 13 items of serum
      proteins--the analytical theory].

PMID- 9190385
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 6. Statistical methods for setting reference
      criteria--Problems].

PMID- 9190386
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 2. The organization and activities of a project
      to set the reference].

PMID- 9190387
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 7. Analysis of physiological factors for
      fluctuations of the 13 items].

PMID- 9190388
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 8. Evaluation of inter-organizational
      discrepancies in the].

PMID- 9190389
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 3. Determination of reference intervals].

PMID- 9190391
TI  - [From sample collection to testing].

PMID- 9190390
TI  - [Standards for ranges of 13 items of blood proteins among Japanese adults-
      results of a joint project of 7 organizations based on NCCLS Document C28-P and
      International Reference CRM470. 9. The background for the basic group composed of
      healthy reference].

PMID- 9190392
TI  - [General tests. C. Effects of a toilet sanitizer on the immunologic fecal occult
      blood reaction].

PMID- 9190393
TI  - [General hematological tests--factors responsible for errors in sampling for
      general hematological tests and their prevention].

PMID- 9190394
TI  - [General hematological tests. A. Effects of the blood sample containers and
      anticoagulants on the determination of lymphocyte surface markers].

PMID- 9190395
TI  - [General hematological tests. B. Evaluation of basophilic fractions by using
      Hemogard Plus].

PMID- 9190396
TI  - [General hematological tests. C. Sampling for bone marrow testing].

PMID- 9190397
TI  - [Blood coagulation tests].

PMID- 9190398
TI  - [Fibrinolysis tests--with special reference to FDP test].

PMID- 9190399
TI  - [Chemical analysis--incidence of sampling errors in clinical chemistry and their
      countermeasures].

PMID- 9190400
TI  - [Blood chemical analysis. A. Effects of sample collection and subsequent
      processing on the test results--determination of blood ammonia level by direct
      deproteinization colorimetry].

PMID- 9190401
TI  - [Blood chemical analysis. B. Stability of ketone bodies in the arterial blood].

PMID- 9190402
TI  - [Blood chemical analysis. C. Key points in sampling for ionized Ca
      determination].

PMID- 9190403
TI  - [Blood chemical analysis. D. Stability of serum lipids and lipoproteins in a
      preserved sample].

PMID- 9190404
TI  - [Blood chemical analysis. E. Effects of human erythrocyte K transport,
      temperature, and drugs on plasma (serum) K value].

PMID- 9190405
TI  - [Blood chemical analysis. F. Fluctuations in the bilirubin contents caused by
      changes in instrument, reagents, and sample containers used in the test].

PMID- 9190406
TI  - [Blood chemical analysis. G. Development of a new blood anticoagulant].

PMID- 9190408
TI  - [Hormone tests. Factors responsible for fluctuations of catecholamine levels].

PMID- 9190407
TI  - [Hormone tests (blood and urine)].

PMID- 9190409
TI  - [From sample collection to testing. B. Evaluation of sample condensation in a
      container without a cover].

PMID- 9190410
TI  - [Tests for immune sera].

PMID- 9190411
TI  - [Immune serum tests. Sampling for complement tests--determination of serum
      complement hemolytic activity (CH50) and problems associated with handling of
      samples].

PMID- 9190412
TI  - [Bacteriological tests].

PMID- 9190413
TI  - [Bacteriological tests: quantitative bacterial cultivation by the spiral system].

PMID- 9190414
TI  - [Virological tests].

PMID- 9190415
TI  - [Tests related to nucleic acids and DNA].

PMID- 9190416
TI  - [Tests related to nucleic acids and DNA: effects of time lag between sample
      collection and examination on HBV-DNA polymerase activity].

PMID- 9190417
TI  - [From sample collection to testing. C. Evaluation of efficacy of blood-collecting
      tubes designed for hemodialysis].

PMID- 9190418
TI  - [TDM and sampling].

PMID- 9190419
TI  - [Transition and the current status of sampling equipment].

PMID- 9190420
TI  - [From sample collection to testing. D. Designing of a transcutaneous blood
      collecting tube].

PMID- 9190422
TI  - [From sample collection to testing. F. Blood specimen collection from newborn
      infants].

PMID- 9190421
TI  - [From sample collection to testing. E. Evaluation of tubes for collecting minute
      quantities of blood for emergency testing of newborn infants].

PMID- 9190423
TI  - [From sample collection to testing. G. Preanalytic phase error in health
      screening tests].

PMID- 9190424
TI  - [Sample handling and risk prevention].

PMID- 9190425
TI  - [Methods to prevent accidental switching of samples].

PMID- 9190426
TI  - [Effects of anticoagulants used at blood specimen collection on clinical test
      results].

PMID- 9190427
TI  - [From sample collection to testing. A. A cover effect of a separating agent in a
      separator-containing vacuum blood-collecting tube].

PMID- 9190428
TI  - [General tests--factors responsible for errors in sampling of urine, feces,
      cerebrospinal fluid, saliva, and other body fluids and prevention of these
      errors].

PMID- 9190429
TI  - [General tests. A. A need for preservatives in saving urinary samples].

PMID- 9190430
TI  - [General tests. B. Effects of bacteria in urinalysis and changes in cellular
      components].

PMID- 9190431
TI  - [The application of molecular biology to thrombosis and hemostasis].
AB  - Current biological science has been revolutionized by a series of new
      investigative molecular techniques developed within the last 15 years. These
      techniques allow the detection of gene mutations responsible for congenital
      diseases including thrombophilia and hemorrhagic disorders. Here, we provide a
      short introduction to polymerase chain reaction (PCR), single-strand
      conformational polymorphism (SSCP), restriction fragment length polymorphism
      (RFLP) and northern blot techniques and present the results of DNA sequence
      analyses of 4 different types of antithrombin III abnormalities and one IIB-type
      von Willebrand disease examined in our laboratory. In addition, we briefly
      summarize the gene mutations reported in patients with activated protein C
      resistance, hemophilia A and hemophilia B.

PMID- 9190432
TI  - [Model for computation of regional cerebral blood flow volume using 123I-IMP].

PMID- 9190433
TI  - [Personal evaluation of the surveillance on tuberculosis and mycobacterial
      infections--is the incidence of tuberculosis declining?].

PMID- 9190434
TI  - [Surveillance on tuberculosis and other infections (Tuberculosis Monthly)].

PMID- 9190435
TI  - [Yield of blood cultures in relation to the cultured blood volume in Bactec 6A
      bottles].
AB  - BACKGROUND: Concentration of microorganisms in blood is low in bacteremia from
      extravascular sources. The best yield from blood cultures is achieved by
      culturing a minimum of 10-20 ml, although in some processing blood culture
      systems such as Bactec NR-860, smaller volume is used. The objectives of the
      present study were to establish the frequency in which inadequate small blood
      volumes are employed for culturing and to analyze the relation between the
      cultured blood volume in Bactec 6A bottles and the yield achieved. MATERIAL AND
      METHODS: We weighed 2000 Bactec 6A bottles pertaining to consecutive blood
      cultures obtained from untreated patients with clinical suspicion of Infection.
      The cultured blood volume was estimated subtracting the mean empty bottle weight.
      RESULTS: Microorganisms were recovered from 251 bottles (12.5%). One hundred and
      thirty one (6.8%) isolates were considered as clinically significant and 115
      (5.7%) as contaminant. The inoculated blood volume in both significant (5.532 +/-
      1.587 ml) and non-significant (5.471 +/- 1.563 ml) recoveries was superior than
      that of bottles without microbiologic growth (5.209 +/- 1.575 ml, p = 0.016 and p
      = 0.06, respectively). A linear positive trend was found between the cultivated
      blood volume and the rate of recoveries (p = 0.008). Within the range of 1 up to
      10 ml, the rate of recoveries increased 2.28% for each additional ml of
      cultivated blood (r = 0.953, p < 0.0001). Out of the 2,000 weighed bottles 127
      (6.3%) contained less than 3 ml of blood and 576 (29%) between 3 and 5 ml.
      CONCLUSIONS: We have proved that the rate of recoveries from Bactec 6A bottles
      increased with the volume of cultured blood. In untreated patients, this increase
      is maintained up to volumes of 7 to 10 ml.

PMID- 9190436
TI  - [One-week treatment with omeprazole, clarithromycin and amoxicillin: high
      efficacy in the eradication of Helicobacter pylori and cicatrization of duodenal
      ulcer].
AB  - BACKGROUND: To evaluate the efficacy of one-week therapy with omeprazole,
      clarithromycin and amoxycillin in eradicating Helicobacter pylori and healing
      duodenal ulcer. PATIENTS AND METHODS: One-hundred and thirty-four consecutive
      duodenal ulcer patients (mean age 47 +/- 13 yrs, 66% males) with H. pylori
      infection were prospectively studied. At endoscopy, biopsies from both gastric
      antrum and body were obtained for histologic study (H/E). A 15C-urea breath test
      was also performed in 98 patients. Omeprazole 20 mg b.i.d., amoxycillin 1 g
      b.i.d., and clarithromycin 500 mg b.i.d. were administered only for 1 week, and
      no therapy was administered thereafter. Endoscopy with biopsies and breath test
      were repeated 1 month after completing therapy. RESULTS: Eradication was achieved
      in 87.3% of patients (n = 93; 95% CI = 82-93%). In the multivariate analysis the
      variables which influenced H. pylori eradication were: time of evolution of ulcer
      disease (p = 0.002) and active chronic gastritis in the antrum (p = 0.04) (chi 2
      model = 15.8; p = 0.001). Ulcer healing was demonstrated in 89.5% of patients (84
      95%), and healing rate was higher when eradication was achieved (94%; 90-98%)
      than in H. pylori-positive patients (59%; 36-78%) (p < 0.001). In the
      multivariate analysis the variables which influenced ulcer healing were: age (p =
      0.02) and H. pylori eradication (p = 0.001) (chi 2 model = 21.2; p = 0.0001). An
      improvement of histologic gastritis was observed when eradication was achieved (p
      < 0.001). Compliance of therapy was complete in all patients but one and no
      relevant adverse effects were reported. CONCLUSION: One-week triple therapy with
      omeprazole, clarithromycin and amoxycillin administered on a twice daily basis
      achieves a high efficacy in eradicating H. pylori and healing duodenal ulcer.
      Moreover, this therapy regimen is simple and is associated with a low incidence
      of adverse effects and a low cost.

PMID- 9190437
TI  - [Changes in insulin secretion in familial combined hyperlipemia].
AB  - BACKGROUND: We have studied the abnormalities in glucose and insulin metabolism
      in a group of nondiabetic subjects with familial combined hyperlipidemia (FCH) in
      order to ascertain the contribution of metabolic risk factors to the elevated
      coronary heart disease incidence observed in FCH. PATIENTS AND METHODS: The study
      includes 42 non-diabetic subjects (25 male and 17 women, mean age 49.1 +/- 9.3
      years), diagnosed with FCH by clinical and analytical studies of the probands and
      first degree relatives. Forty two control subjects of similar age, sex and body
      weight were also studied. In both groups plasma lipids and lipoproteins, plasma
      glucose and insulin basal and after oral glucose tolerance test (OGTT) were
      studied. RESULTS: The mean age, BMI and the separation by gender was similar in
      the two groups. The mean systolic and diastolic blood pressures were higher (p <
      0.01) in the FCH group compared with controls (145.4/90.1 and 131.5/76.3 mmHg,
      respectively). The levels of lipids and apo B were also higher in the FCH group.
      The plasma glucose values were significantly higher at 30, 60, 90 and 120 minutes
      during OGTT and the plasma insulin at 0, 60, 90 and 120 minutes of OGTT in FCH
      respect to controls. The area under the curve of the secretion of insulin was
      11652.0 +/- 2281.1 and 7205.4 +/- 2289.1 pmol/l/min in FCH and controls (p <
      0.01), respectively. The percentage of subjects with basal hyperinsulinemia was
      66.6% in the FCH group and 9.5% in the controls (p < 0.01); at 2 hours OGTT,
      78.5% and 9.5% in FCH and controls, respectively (p <0.01). The insulin secretion
      was significantly related with the plasma triglycerides levels, cholesterol
      bourded to very low density lipoproteins and systolic and diastolic blood
      pressure. CONCLUSIONS: Hyperinsulinism is a frequent finding in non-diabetic
      subjects with FCH, both with normal and abnormal glucose tolerance and could
      contribute to the high incidence of cardiovascular risk in these patients.

PMID- 9190438
TI  - [Blood cultures in the polymerase chain reaction age].

PMID- 9190439
TI  - [Transmission of viral hepatitis from the physician to the patient: an
      exceptional circumstance].

PMID- 9190441
TI  - [Triplet repeat expansions in hereditary neurodegenerative diseases].

PMID- 9190440
TI  - [Diagnosis of renovascular disease by heart catheterization].
AB  - Atherosclerotic renovascular disease is a common entity, particularly in persons
      older than 50 years of age and especially in those patients with other evidence
      of atherosclerotic vascular disease. The illness clearly progresses in some
      patients, and progression rate appears to be highly variable. Taken into account
      the apparent high prevalence of renovascular disease in older persons, it is
      possible that this disorder be the cause of end stage renal disease in 5% to 15%
      of patients currently entering the dialysis program each year. Surgery and
      percutaneous angioplasty can both improve renal function in patients with renal
      artery stenosis. We describe a patient in whom the detection of renovascular
      disease was made accidentally at the time of coronary arteriography. He presented
      an acute renal failure after use of angiotensin-converting enzyme inhibitors
      and/or contrast media associated nephrotoxicity, and was treated with
      percutaneous transluminal balloon angioplasty and had a successful outcome.

PMID- 9190442
TI  - [Left hemiparesis with atypical course in a 79-year-old man (clinico-pathologic
      conference)].

PMID- 9190443
TI  - [Contribution of liver transplantation to the scientific production of a
      hospital].

PMID- 9190444
TI  - [Burkitt's lymphoma with onset in the thyroid gland. A case report].

PMID- 9190445
TI  - [Isolated ACTH deficiency associated with partially empty sella turcica].

PMID- 9190446
TI  - [Economic costs of autologous hematopoietic progenitor cell transplantation].

PMID- 9190448
TI  - [Ethical scrutiny of medical research on humans. Legislation is necessary!].

PMID- 9190447
TI  - [The refugee problem and cost savings challenge medical ethics. A new Internet
      forum may be instructive].

PMID- 9190449
TI  - [Medical ethics and refugee politics. A statement from the Medical Society is
      needed].

PMID- 9190450
TI  - [The absolute truth about snuff is often a utopia].

PMID- 9190451
TI  - [Why is the Riskronden not distributed to all physicians?].

PMID- 9190453
TI  - [Misleading information about examination and treatment of urinary tract
      infections!].

PMID- 9190452
TI  - [Private practitioners see through Ringholm's demagogy].

PMID- 9190454
TI  - [A pearl in the nose--can it be "cured" with white pepper?].

PMID- 9190455
TI  - [Avoid physicians' beepers!].

PMID- 9190456
TI  - [Chloroquine resistance and prophylaxis].

PMID- 9190457
TI  - [New series: action mechanisms of drugs].

PMID- 9190458
TI  - [New tests for diagnosis of primary aldosteronism].

PMID- 9190459
TI  - [Varying success in manifest or occult mental retardation. Mildly retarded
      individuals obtained permanent employment].

PMID- 9190461
TI  - [Pulmonary atresia with intact ventricular septum. A congenital heart defect with
      improved prognosis].

PMID- 9190460
TI  - [Selective inhibitors of cyclooxygenase-2. New agents against pain and
      inflammation].
AB  - Peripherally active analgesics are considered to exert their effect by blocking
      the enzyme, cyclo-oxygenase (COX), thus inhibiting the biosynthesis both of
      prostaglandins and of thromboxanes. It was recently found that there are two
      enzymes which can form prostaglandins: COX-1 and COX-2. Whereas COX-1 is normally
      expressed in many tissues, expression of COX-2 can be induced in response to
      inflammation. New experimental findings in 'knockout' mice have suggested that
      subgrouping of cyclo-oxygenases as 'good' (COC-1) and 'bad' (COX-2) may be
      inappropriate. COX-2 specific NSAIDs (non-steroidal anti-inflammatory drugs) may
      be potent antiinflammatory and analgesic agents with no serious side-effects,
      though this has yet to be confirmed in clinical trials.

PMID- 9190462
TI  - [Resources for the surgery of heart defects in children. Now the there is a
      better way to use the records].

PMID- 9190463
TI  - [Severe adverse effect of methotrexate in rheumatoid arthritis. Don't forget
      security routines in intercurrent disease!].

PMID- 9190464
TI  - [A case report: abdominal pain of TBC was misjudged as urethritis].

PMID- 9190465
TI  - [Poor quality of care of asthmatic patients].

PMID- 9190467
TI  - [John Locke, physician and philosopher. "The most sensible man on earth"].

PMID- 9190466
TI  - [Migration of an aspired piece of plastics. ECMO in respiratory failure optimizes
      bronchoscopy].

PMID- 9190469
TI  - [Decentralized drug budget. Distribute resources in primary health care].

PMID- 9190468
TI  - [The physician and the computer--a view at the grass-root level. Central
      coordination is needed for the IT system in health care].

PMID- 9190470
TI  - [Sick-listing rules a modern precipice].

PMID- 9190471
TI  - [Ampicillin esters are environment friendly].

PMID- 9190472
TI  - [A reminder of bleeding risk with diclofenac administration].

PMID- 9190473
TI  - [A serious debate on euthanasia requires counter-arguments based on facts].

PMID- 9190474
TI  - [Medicine needs critical reflections!].

PMID- 9190475
TI  - [Epilepsy care. Not only a question of reducing seizures].

PMID- 9190476
TI  - [Promising effects of the new antipsychotic agents in schizophrenia. But
      recommendations of the Medical Products Agency are conservative].

PMID- 9190477
TI  - [Radiotherapy of lung cancer. Optimized radiotherapy improves survival].

PMID- 9190478
TI  - [An attempt to evaluate intervention. A questionnaire about the smoking habits
      school children].

PMID- 9190479
TI  - [Warning signals in acute abdominal disorders. Lactate is the best marker of
      mesenteric ischemia].
AB  - An increased plasma lactate concentration (PLC) is a recognized danger signal
      often found in cases of shock, septicaemia, hepatic and renal failure, and
      diabetic ketoacidosis. In 120 patients with abdominal complaints, we found the
      PLC to be above normal limits in 96 per cent (24/25) of the mesenteric ischaemia
      subgroup, in all 20 of the general bacterial peritonitis subgroup, in 30 per cent
      (6/20) of the acute pancreatitis subgroup, and in about half of the 25 cases of
      intestinal obstruction. In all other abdominal conditions represented (n = 30),
      comprising various inflammatory or infectious abdominal diseases, the PLC was
      within the normal range. In patients with abdominal complaints, an increased PLC
      usually indicates the needs of emergency surgery. In the present series, the PLC
      manifested a sensitivity of 96 per cent and a specificity of 38 per cent as a
      marker of mesenteric ischaemia, and was also found to be a useful aid in the
      diagnosis of bowel obstruction and general bacterial peritonitis.

PMID- 9190480
TI  - [Epidemiology in epilepsy. Epilepsy primarily affects small children and the
      elderly].
AB  - Epilepsy is one of the commonest neurological/disorders, with peak incidences
      among the elderly and among children in the first year of life. Approximately
      60,000 (0.7 per cent) of the Swedish population, 50,000 adults and 10,000
      children, have active epilepsy. Stroke is the aetiology most commonly identified.
      The majority of those with a first-ever unproven seizure suffer no further
      seizures. Of those who do have further seizures (i.e., who develop epilepsy), 65
      85 per cent eventually become free from seizures, and many of them are able to
      cease antiepileptic medication. Epilepsy is a heterogeneous disorder. The larger
      proportion of patients who are otherwise healthy, and who respond readily to
      antiepileptic treatment and manifest no side effects or only mild ones, are
      characterised by the best prognosis and are able to terminate treatment within 2
      5 years without recurrence. At the other extreme is the smaller group of patients
      with onset of epilepsy very early in life, and characterised by multiple severe
      neurological defects, severe daily seizures, resistance (more or less) to all
      available treatment, and high mortality. In many cases of epilepsy, however,
      severity and prognosis lie somewhere between these two extremes.

PMID- 9190481
TI  - [The "green keyhole" project for public health. The effect of society's impact on
      health is difficult to measure].

PMID- 9190482
TI  - [Controlling of intrauterine devices should increase in Sweden].

PMID- 9190483
TI  - [Patients with diabetes: eye examination should be done prior to ECT].

PMID- 9190484
TI  - [A unique chance to study breast cancer. A Saudi Arabian hospital concentrates on
      treatment and research].

PMID- 9190485
TI  - [The importance of follow-up of wound infections. 100 percent registration at the
      Ostra hospital in Gothenburg].

PMID- 9190486
TI  - [Dfferent priorities in ambulance transportation. High competence is necessary
      for everybody].

PMID- 9190487
TI  - [Laboratory training--a learning aid].

PMID- 9190488
TI  - Keep guard up against HIV-1-related lung infections, say experts.

PMID- 9190490
TI  - [Tumor disseminate in site following laparoscopic cholecystectomy].

PMID- 9190489
TI  - Confidentiality at risk in the electronic age.

PMID- 9190491
TI  - [Evaluation of ischemic liver reperfusion injury by plasma phosphatidylcholine
      hydroperoxide].

PMID- 9190492
TI  - Tobacco litigation.

PMID- 9190493
TI  - Tobacco litigation.

PMID- 9190494
TI  - Tobacco litigation.

PMID- 9190495
TI  - Tobacco litigation.

PMID- 9190496
TI  - Induced abortion and the risk of breast cancer.

PMID- 9190497
TI  - Induced abortion and the risk of breast cancer.

PMID- 9190498
TI  - Early ERCP and papillotomy for acute biliary pancreatitis.

PMID- 9190499
TI  - Early ERCP and papillotomy for acute biliary pancreatitis.

PMID- 9190500
TI  - Acute pancreatitis during primary HIV-1 infection.

PMID- 9190501
TI  - Propagation of a human herpesvirus from AIDS-associated Kaposi's sarcoma.

PMID- 9190502
TI  - Prevention of atherosclerosis in coronary-artery bypass grafts.

PMID- 9190503
TI  - Cost effectiveness of coronary bypass surgery versus angioplasty.

PMID- 9190504
TI  - Access to health care for women.

PMID- 9190505
TI  - [Protection against diphtheria].
AB  - An epidemic of (lethal) diphtheria emerged a few years ago in the former Soviet
      Union where the vaccination density was low. In order to prevent an outbreak in
      the Netherlands after import of diphtheria, the Health Council went into the
      degree of protection and measures to increase it. At least one-third of the
      population are protected insufficiently; they have neither been re-vaccinated in
      time, nor have they built up immunity by circulation of Corynebacterium strains.
      Education and (re-)vaccination of risk groups. such as persons having been in
      contact with an index patient, would appear to be adequate measures.

PMID- 9190506
TI  - [Micropenis in children: etiology, diagnosis and therapy].
AB  - The term 'micropenis' is applied if the measured penile length is more than 2.5
      standard deviations below the mean for the age; in neonates born at term this
      means a penile length of less than 2 cm. Micropenis is the consequence of a
      defect which develops after the 14th week of pregnancy. The cause may be hormonal
      (hypothalamo-hypophysial (hypogonadotropic hypogonadism), testicular
      (hypergonadotropic hypogonadism) or end organ resistance), but also iatrogenic
      (medication during the pregnancy). In addition, micropenis occurs as a part of a
      number of syndromes. The diagnostic investigation comprises history-taking,
      physical examination, specific hormonal testing and, if considered necessary,
      chromosomal and imaging examinations. In the treatment of micropenis, a trial
      treatment with testosterone plays an important part.

PMID- 9190507
TI  - [Clinical judgement and decision making in practice. A patient with hemoptysis].
AB  - A 43-year-old man was admitted because of severe and recurring haemoptysis, which
      was eventually ascribed to Goodpasture's syndrome. In case of an aspecific sign
      such as haemoptysis experienced clinicians will try to restrict the differential
      diagnosis by concentrating on other signs that are relevant to the main problem.
      In haemoptysis these other signs are general illness, fever, shortness of breath,
      painful respiration, chronic productive cough, and signs or a history of cardiac
      or pulmonary disease. If the differential diagnosis consists mainly of rare
      disorders or rare manifestations of common disorders, all possibilities should be
      considered. If Goodpasture's syndrome is suspected, further specific diagnostic
      tests should be done without delay.

PMID- 9190508
TI  - [Acute asthma in children; guidelines by pediatric pulmonologists for diagnosis
      and treatment].
AB  - The diagnostic phase in a child with acute asthma should be short and comprise a
      brief history-taking, inspection and auscultation of the thorax, transcutaneous
      oxygen measurement and, if possible, peak flow measurement. Blood picture. sputum
      culture and chest X-ray may be included in the diagnostics if indicated. The
      primary treatment consists of administration of bronchodilators (beta-2
      sympathicomimetics) by inhalation, using a spacer. Repeated inhalation of
      salbutamol and ipratropium may be necessary. In case of inadequate improvement
      (spraying necessary every 3 hours for 24-48 hours), hospitalization and systemic
      administration of corticosteroids are indicated. Other reasons for
      hospitalization are a transcutaneous oxygen saturation lower than 91%,
      complications such as subcutaneous emphysema and pneumothorax, exhaustion of
      child or parents, and rapid aggravation of the clinical picture with rising Pco2
      and falling pH in capillary or arterial blood.

PMID- 9190509
TI  - [Mohs' method of micrographic surgery as treatment for recurrent basal cell
      carcinoma].
AB  - OBJECTIVE: Evaluation of Mohs' micrographic surgery as treatment for recurrent
      basal cell carcinoma of the skin. DESIGN: Retrospective. SETTING: University
      Hospital Maastricht, the Netherlands. METHOD: In the period April 1992 to
      December 1995, 91 recurrent basal cell carcinomas (88 patients) were treated by
      Mohs' micrographic surgery. Medical records were analysed retrospectively with
      respect to different aspects. RESULTS: The mean age of the patients was 69 years.
      The recurrent basal cell carcinomas, with an mean diameter of 19.7 mm, were
      mainly localized on the nose and forehead. There were equal numbers of solid and
      morphea-like types of basal cell carcinomas. Most of these tumours had been
      treated by means of surgical excision in the past. The last treatment had taken
      place 3 years previously on average. Reconstruction was performed by means of
      primary closure, a graft or a flap. The mean follow-up period after Mohs'
      micrographic surgery was 12 months, in which one tumour recurred. CONCLUSION:
      Mohs' micrographic surgery is a surgical technique which provides the best
      prospect of total tumour removal together with maximal functional and cosmetic
      preservation. Mohs' micrographic surgery is of particular value for the treatment
      of recurrent basal cell carcinomas.

PMID- 9190510
TI  - [Favorable effects of breathing and relaxation instructions in heart
      rehabilitation: a randomized 5-year follow-up study].
AB  - OBJECTIVE: To determine the effect of breathing and relaxation instruction of
      patients after a myocardial infarction on the occurrence of cardiac events during
      5 years. DESIGN: Prospective randomised. SETTING: Kennemer Gasthuis, Haarlem, the
      Netherlands. METHOD: In the period 1981-1983, 156 myocardial infarction patients
      were randomly assigned to either rehabilitation plus relaxation therapy (six
      weekly sessions of breathing and relaxation instruction) (n = 76) or cardiac
      rehabilitation alone (n = 80). The occurrence of cardiac events and the amount of
      medical consumption on the two treatments was compared during 5 years. RESULTS:
      At five-year follow-up, 12 cardiac deaths had occurred, 5 in the relaxation group
      and 7 in the control group, reinfarction was observed in 10 and 12 patients, and
      cardiac surgery was performed in 2 and 11, respectively. In total 15 (20%) and 26
      patients (33%), respectively, had at least one of these events (odds ratio (OR)
      for the relaxation group: 0.51; 95% confidence interval (CI): 0.25-1.06). Medical
      consumption (counted as cardiac events and cardiac hospitalisations) was 30
      patients (39%) experiencing 52 cardiac events in the relaxation group, for which
      the patients were hospitalized for a total of 476 days, and 38 patients (48%)
      experiencing 78 cardiac events in the control group (OR: 0.72; 95% CI: 0.38-1.36)
      with a total of 719 hospitalisation days; the total number of hospitalisations
      was reduced by 31% by relaxation instruction. CONCLUSION: In the long run, the
      disease course after myocardial infarction is probably influenced favourably by
      adding relaxation instruction to cardiac rehabilitation. The extra costs are
      compensated for by a decrease in hospitalisation for cardiac problems.

PMID- 9190511
TI  - [Spondylodiscitis caused by Streptococcus agalactiae].
AB  - Two previously healthy adults, a man aged 69 and a woman aged 51 years, presented
      with spondylitis caused by Streptococcus agalactiae. One patient had fever and
      acute pain in the neck, the other progressive pain in the lower back. From
      cultures of blood and bone respectively. S. agalactiae was isolated. Both
      patients recovered after treatment with benzylpenicillin. S. agalactiae (group B
      streptococcus) is a wellknown cause of invasive infections in neonates and
      pregnant adults. Infections in nonpregnant adults are increasingly reported.
      Chronic conditions such as diabetes mellitus are strongly associated with disease
      caused by S. agalactiae.

PMID- 9190512
TI  - [Microscopic tumor embolisms in metastasized breast carcinoma].
AB  - In two patients, women of 54 and 46 years old, with metastatic carcinoma of the
      breast, multiple microscopic tumour emboli in the lungs were found at autopsy.
      Ante mortem, unexplained respiratory distress in the former and an atypical
      thrombotic thrombocytopenic purpura-like syndrome in the latter were the most
      characteristic clinical features. Pulmonary microscopic tumour embolism is a rare
      diagnosis but it may occur in all types of cancer. Clinically, thrombotic
      pulmonary emboli are difficult to distinguish from microscopic tumour embolism.
      Special attention is to be paid to typical findings on radionuclide perfusion
      lung scanning (multiple subsegmental perfusion defects at the periphery of the
      bronchopulmonary segments with a normal ventilation named "segmental contour
      pattern'). Microangiopathic haemolytic anaemia and consumption coagulopathy are
      associated disorders. Tumour-directed therapy is the treatment of choice.

PMID- 9190513
TI  - [Severe hepatitis attributed to paroxetine (Seroxat)].
AB  - A 52-year-old man suffering from chronic hepatitis B related liver cirrhosis was
      treated for depression with paroxetine (Serotax) 5 mg and subsequently 15 mg once
      daily. A severe hepatitis with liver failure (jaundice, hypoalbuminaemia, edemas,
      and ascites) developed. After the drug was withdrawn the patient recovered
      completely. The adverse reaction may be explained by a change in the
      pharmacokinetics of the drug caused by the liver cirrhosis. Caution is required
      in prescribing long-term paroxetine therapy for patients with documented liver
      cirrhosis. The liver function should be monitored and administration of the drug
      should be discontinued when functional disturbances are noticed.

PMID- 9190514
TI  - [Pieter van Foreest: physician on the threshold of a new era].
AB  - In a variety of ways attention is being drawn nowadays to the fact that Pieter
      van Foreest (1521-1597) died four hundred years ago. The question arises,
      however, whether such a comprehensive commemoration is justified by Van Foreest's
      contribution to the development of medical science. Medical history certainly
      does not attribute concrete substantial new findings to his name. Nevertheless,
      he earned the longstanding epithet 'Dutch Hippocrates' by his writings.
      Especially, his Observationes et curationes medicinales c.q. chirurgicales
      remained on vogue for some centuries after his death, mainly due to the accurate
      description of symptomatology of a wide variety of diseases. Van Foreest should
      be considered as a conspicuous representative of the new empirical medicine which
      gained favour after the humanistic rediscovery of the classical Greek authors,
      especially Hippocrates.

PMID- 9190515
TI  - [How meaningful is the aspiration of injection solution after inserting the
      injection needle for the intramuscular administration of vaccines?].

PMID- 9190516
TI  - [Is smoking cigars or pipes harmful?].

PMID- 9190517
TI  - [The floating kidney].

PMID- 9190518
TI  - [The floating kidney].

PMID- 9190519
TI  - [Sleeping disorders rarely come singly].
AB  - Four patients, a woman aged 60 and three men aged 61, 53 and 56 years, presented
      with hypersomnia during the day. The cause was determined by polygraphic
      registration and was a variable combination of sleep apnoea syndrome, narcolepsy
      and periodic movements of the limbs in sleep syndrome (PMLS). Such a combination
      may lead to a therapeutic paradox as the treatment of one disturbance may lead to
      aggravation of another one. Therapy is possible but only when it is completely
      clear which component of the disorder prevails. Whole night polygraphy is
      indispensable for this approach.

PMID- 9190520
TI  - [Structured care for stroke patients: stroke units and transmural stroke
      services].
AB  - Following the successful introduction of Coronary Care Units for patients after a
      myocardial infarction, Stroke Units were designed where the specialized care for
      patients who had suffered a stroke might be concentrated. A meta-analysis in 1993
      indicated that patients indeed benefited from treatment in such a unit. Stroke is
      the third cause of death in the Netherlands, with a prevalence in people aged 55
      and more of 3.5% in men and of 1.9% in women. A Stroke Unit is part of a
      hospital; a Transmural Stroke Service in which neurologists and general
      practitioners participate, may deliver the appropriate care in the appropriate
      setting: patients may quickly be admitted to the hospital, an outpatient clinic
      can limit unnecessary hospitalization, and the general practitioner supervises
      chronic home treatment. The possibilities are there, now they have to be
      implemented.

PMID- 9190521
TI  - [Treatment of stroke in Europe: the Helsingborg Declaration].
AB  - Late in 1995, the Helsingborg Declaration was adopted, a European consensus text
      on the basic elements for policy in, and objectives of treatment of strokes. This
      declaration was prompted by the fact that the differences in incidence in
      different European countries, and the changes of the incidence in the course of
      the years suggest a great importance of environmental factors that can be
      influenced. The organizers of this consensus meeting might have enhanced the
      value of the document by more exactly indicating the (scientific) strength of the
      argumentation for each recommendation. Nevertheless, many of the recommendations
      are based on solid evidence. A plea is made to structure stroke care, measure the
      quality of care, facilitate early diagnosis and therapy after stroke, improve the
      possibilities for rehabilitation, and apply appropriate secondary prevention.

PMID- 9190522
TI  - [Contact allergy for perfume ingredients in cosmetics and toilet articles].
AB  - Fragrance materials are not only present in products primarily used for their
      scent such as perfume, eau de toilette, deodorant and aftershave, but also in
      cosmetics, toiletries, household products and industrial materials. Of the
      general population, approximately one percent are allergic to fragrance
      materials, men nearly as frequent as women. Of patients consulting the
      dermatologist because of dermatitis, 6-11% have a positive patch test to the
      fragrance mix. Allergic contact dermatitis due to fragrances usually consists of
      erythema and desquamation, often localized in the neck, behind the ears, in the
      arm-pits or around the eyes. It can worsen pre-existing dermatoses such as hand
      eczema, atopic dermatitis, perianal dermatitis or vulvar dermatitis. The
      diagnosis of contact allergy to fragrances is made by epicutaneous tests with the
      European standard series (including some markers for fragrance sensitivity: the
      fragrance mix, balsam of Peru and colophony) and the patient's own contact
      materials. A positive patch test reaction must be followed by evaluation of its
      relevance. Advice to the patient is directed towards avoidance of fragranced
      products, if possible, and explanation of how use tests can identify fragranced
      products which can be used without ill effects.

PMID- 9190523
TI  - [Controversies in hospital guidelines for non-resuscitation decisions].
AB  - Guidelines regarding non-resuscitation decisions sometimes raise conceptual and
      ethical questions. Establishing blood circulation and gas exchange is no useful
      criterium to determine the efficacy of resuscitation. A professional assessment
      of efficacy or medical futility of resuscitation may involve value judgements.
      These value judgements should not concern the life of the individual patient, but
      rather the objective of resuscitation in general. Furthermore, these judgements
      ought to be grounded on professional consensus. A patient should be informed of a
      non-resuscitation decision that has been taken, since in the normal course of
      events resuscitation is the correct treatment. Furthermore, a conversation serves
      not only to obtain informed consent but also to align the views and expectations
      of the patient and his treating physician. Suspension of a non-resuscitation
      policy during operations should be discussed with the patient. A physician is
      allowed to define the limits to the risks to which he wants to expose the
      patient.

PMID- 9190524
TI  - [Reserve concerning pulmonary angiography in pulmonary embolism is not
      justified].
AB  - OBJECTIVE: Evaluation of the safety of pulmonary angiography in patients with
      clinically suspected pulmonary embolism. DESIGN: Retrospective cohort study.
      SETTING: Academic Hospital, Rotterdam, the Netherlands. METHOD: The data on
      complications of pulmonary angiography were collected from four Dutch hospitals
      over a period of about five years (Academic Medical Centre and Slotervaart
      Hospital, Amsterdam; St. Elisabeth Hospital, Tilburg and Dr. Daniel den Hoed
      Cancer Centre/University Hospital Rotterdam). RESULTS: Pulmonary angiography was
      performed in 697 patients. No fatal complications were noted (mortality: 0%; 95%
      confidence interval (95% CI); 0.00-0.53). Complications were seen in 3 patients;
      dissection of the pulmonary artery in I patient and contrast extravasation in 2
      patients (morbidity: 0.4%; 95% CI: 0.09-1.25). CONCLUSION: In patients with
      clinically suspected pulmonary embolism, pulmonary angiography is a safe
      diagnostic modality. It is recommended that, in patients in whom the diagnosis of
      pulmonary embolism cannot be confirmed or excluded by noninvasive diagnostic
      methods, pulmonary angiography should be performed (according to the Dutch
      consensus "Diagnostic pulmonary embolism').

PMID- 9190525
TI  - [Tuberculosis in asylum seekers in The Netherlands].
AB  - OBJECTIVE: To compare data of some features and treatment results of asylum
      seekers with TB in whom the diagnosis was made by a roentgenologic examination of
      the thorax a short time after arrival in the Netherlands with data of other TB
      patients. DESIGN: Retrospective. SETTING: The Netherlands. METHOD: Data of
      patients with tuberculosis are collected in the National Tuberculosis Register.
      In 1993 this register included data of 1582 patients, among them III asylum
      seekers in whom TB was diagnosed after obligatory roentgenologic screening a
      short time after arrival in the Netherlands. The reason for examination, presence
      of complaints, forms of tuberculosis, presence of bacteriological confirmation,
      drug-resistance and results of treatment of them were compared with the data of
      other asylum seekers (n = 169) and other TB-patients (n = 1302). RESULTS: The
      diagnosis TB in asylum seekers who are screened obligatorily was
      bacteriologically confirmed in 34 of III (31%) of the cases, while in 72 of 169
      (43%) other asylum seekers and in 729 of 1302 (56%) of the other TB-patients (p <
      0.001 for the difference between obligatory screened asylum seekers and other TB
      patients). Resistance against isoniazide and streptomycin was more frequent in
      asylum seekers (n = 106; 13% and 19% respectively) than in Dutch patients (n =
      338; 2% and 3% respectively) (p < 0.001). Obligatory screened asylum seekers with
      bacteriologically confirmed TB were cured in 82% of the cases and this did not
      differ from the other groups. Asylum seekers and other immigrants showed a higher
      default-rate than Dutch patients did (p < 0.001). CONCLUSION: Among asylum
      seekers with tuberculosis discovered by the first obligatory screening was a
      lower percentage of bacteriological confirmation and a higher percentage of drug
      resistance and defaulters. The results of treatment of asylum seekers with
      bacteriologically confirmed TB were good.

PMID- 9190526
TI  - [Transverse presentation due to coprostasis].
AB  - A multiparous woman was admitted at 32 weeks to evaluate the reason for a
      persistency in transverse lie. Ultrasound examination at 25 and 32 weeks revealed
      a circular echogenic structure near the cervix. It was considered to be a
      fibroid. At rectovaginal examination a compact faecal mass was identified. The
      woman never had complained of abnormal bowel function: however, daily diarrhoea
      had occurred since 3 months gestational age. Several times it was necessary to
      apply oil rectally for softening, enabling digital faecal extraction; phosphate
      enemas and warm water enemas led to considerable faeces production. Near term a
      healthy daughter was delivered vaginally. Chronic constipation was diagnosed,
      worsened by pregnancy and an inadequate diet.

PMID- 9190527
TI  - [Linguistics in blood group serology].
AB  - With a view to terminological uniformity, blood group serologists, immunologists
      and transfusion physicians should refer only to the "ABo' (zero) in stead of the
      "ABO' system. They also should use "HLA antibodies' in stead of "anti HLA
      antibodies'. The new Dutch spelling "resus' in stead of "Rhesus' is incorrect
      from a historical point of view.

PMID- 9190528
TI  - [Short lingual frenum].

PMID- 9190529
TI  - [Short lingual frenum].

PMID- 9190530
TI  - [Short lingual frenum].

PMID- 9190531
TI  - [Short lingual frenum].

PMID- 9190532
TI  - [Depression following a first heart infarct; similarities with and differences
      from 'ordinary' depression].

PMID- 9190533
TI  - [Mycobacterium avium infection in HIV-infected patients: epidemiology, diagnosis,
      prevention and treatment].

PMID- 9190534
TI  - [Congenital nephrogenic diabetes insipidus: a difficult diagnosis?].
AB  - In five patients (a boy aged 10 years, a boy aged 3 months, his brother aged 1
      week, the brother of the mother of the last-mentioned two boys who had died at
      the age of one, and a girl of kindergarten age) congenital nephrogenic diabetes
      insipidus was diagnosed. This rare syndrome (prevalence 1:500,000) is caused by
      renal insensitivity to the antidiuretic hormone arginine vasopressin. In infancy
      the symptoms of this disorder are aspecific, and the main symptoms of the
      disease, polyuria and polydipsia, often remain unnoticed at this young age. A
      simple anamnesis and a few laboratory tests should suggest the diagnosis. Early
      diagnosis and genetic counselling are possible as the molecular effects involved
      have been elucidated.

PMID- 9190535
TI  - [Creutzfeldt-Jakob disease; one year later].
AB  - During the last year the knowledge of the transmission of prion diseases has
      increased. New diagnostic methods were developed: investigation of cerebrospinal
      fluid for the 14-3-3 protein and tonsillar biopsy to detect protease resistant
      prion protein. Indirect evidence of a causal relation between new variant
      Creutzfeldt-Jakob disease (nvCJ) and bovine spongiform encephalopathy (BSE) is
      accumulating, although epidemiological data do not indicate that the incidence of
      CJ is increasing.

PMID- 9190536
TI  - [Malignant hyperthermia as a complication of anesthesia: predisposition is
      hereditary].
AB  - The frequency of malignant hyperthermia in the Netherlands is about 1 in 200,000
      anaesthesias. Five times a year, an anaesthetic procedure will be complicated by
      a malignant hyperthermic metabolic disturbance, which can cause death if
      treatment is not instituted rapidly, by the administration of dantrolene.
      Suxamethonium and all the anaesthetic vapours can trigger such a reaction.
      Malignant hyperthermia patients are healthy patients who have a mutation of the
      ryanodine receptor gene RYR. Predisposition to malignant hyperthermia is
      inherited as an autosomal dominant condition. So far a genetic malignant
      hyperthermia test is not available because of genetic heterogeneity. The in-vitro
      contracture test in skeletal muscle is currently used as a diagnostic test for
      malignant hyperthermia. Patients who are likely to be at risk based on a clinical
      grading score, and family members with at least a 25% chance of inheriting
      malignant hyperthermia, are eligible for this test.

PMID- 9190538
TI  - [Referral to a clinical-genetic center for genetic counseling in mental
      disorders].
AB  - OBJECTIVE: Evaluation of the genetic counselling for psychiatric disorders in a
      clinical genetic service. DESIGN: Retrospective. SETTING: Clinical Genetic
      Service Rotterdam, the Netherlands. METHOD: Evaluation of the psychiatric genetic
      counselling during the period 1985-1992 (n = 49). RESULTS: Psychiatric disorders
      were the indication for genetic counselling in 1%. A minority of the consultants
      were referred by the psychiatrist. The most common question was the risk of
      future children becoming affected by a psychiatric disorder already present in
      the family. The male-female ratio was about one for the whole group of
      consultants. Affected relatives were significantly more frequent in the woman's
      family than in the man's. The average number of affected individuals in a family
      was 3.6. CONCLUSION: Genetic counselling for psychiatric disorders in a clinical
      genetic service is requested infrequently considering the frequency of these
      problems. This may be related to a lack of need for information and counselling
      in potential consultants or to adequate information by treating physicians, but
      also to insufficient recognition by general practitioners and psychiatrists of
      questions patients and their family have.

PMID- 9190537
TI  - [Molecular-genetic aspects of neurofibromatosis].
AB  - Two forms of neurofibromatosis, type 1 (NF1) and type 2 (NF2) are connected with
      genes localized on chromosomes 17 and 22, respectively. The genes that are
      inactivated in neurofibromatosis code for the proteins neurofibromine and
      merline, respectively. Since inactivation leads to neoplasia, they are called
      tumour suppressor genes. Neurofibromine shows resemblances to proteins that serve
      to inactivate oncogenes. Merline has a relationship with proteins that connect
      the cytoskeleton and the cell membrane. The precise function of the proteins is
      still unknown. The NF1 gene is characterized by extraordinarily high sensitivity
      to mutation; half the NF1 patients have not inherited the disease. In the
      familial form of neurofibromatosis, a mutated gene is inherited and the normal
      allele in the tumour is inactivated, making tumour growth possible. In the
      sporadic form of neurofibromatosis, both normal alleles are inactivated locally
      in the tissue so that a tumour develops in that place.

PMID- 9190539
TI  - [Variable rates of diseases in health survey and family practitioners'
      registries].
AB  - OBJECTIVE: To compare the data from the health survey of the Central Bureau for
      Statistics (CBS: about episodes of chronic diseases experienced by those
      questioned) and from general practice registration projects (regarding episodes
      of care). DESIGN: Descriptive. SETTING: Department of General Practice, Academic
      Medical Centre, Amsterdam, the Netherlands. METHOD: Frequency figures from the
      CBS health survey regarding chronic diseases for 1992 were compared with data
      from three large continuous general practice registration projects: the Amsterdam
      Transition Project, the Nijmegen Continuous Morbidity Registration and the fourth
      British National Morbidity Study. From the Transition Project not only one-year
      data were used but also data referring to a four-year period (1989/'93). RESULTS:
      Incidence and prevalence figures concerning illness and care were in good
      agreement regarding cardiovascular diseases, uterine prolapse, diabetes mellitus,
      thyroid disorders, epilepsy and cancer. The health survey had higher frequencies
      than the GP registration for respiratory disorders, hypertension (both mostly in
      the age group 25-44 years) gastrointestinal disorders, articular disorders and
      migraine. With regard to a number of diseases, the four-year registration was in
      better agreement with the health survey than the one-year registration (e.g.
      joint disorders): with other disorders the reverse was true (e.g. stroke).
      CONCLUSION: There were similarities as well as differences between the
      frequencies from the health survey and the general practice registration
      projects. Regarding a number of these differences interpretation was possible by
      using not only one-year data from the GP practice but also data concerning a
      longer period (4 years) and by comparing the information for different age
      groups.

PMID- 9190540
TI  - [Neurofibromatosis type 2].
AB  - Neurofibromatosis type 2 (NF2) is a complex and progressively disabling disease,
      resulting from development of multiple central nervous system tumours. Two case
      studies, one of a woman who suffered hearing problems from the age of 17 and one
      of a man with cataract as the first symptom at the age of five, illustrate the
      complex course of the disease. The first patient died of her disease, the second
      due to a traffic accident. It is necessary to anticipate the frequent development
      of new neoplasms. The regular communication between the various disciplines
      involved in the patient's care is instrumental to reach this goal. This
      multidisciplinary approach should also play a part in the screening of patients
      at risk for NF2.

PMID- 9190541
TI  - [Peer review in requests for subsidy].
AB  - There is peer review by scientific journals and by fund granting institutions.
      The former is usually a very thorough procedure with the authors being informed
      of the reasons for rejection of the article, whereas the latter often leaves the
      applicants with doubts as to the thoroughness and the fairness of the procedure.
      It is suggested that grant peer review follow the rules for scientific journal
      peer review including information of the applicants of the referees' findings and
      opinions. Moreover there is a need for an ombudsperson to deal with complaints.

PMID- 9190542
TI  - [Psychiatric disorders and somatic diseases].

PMID- 9190543
TI  - [Psychiatric disorders and somatic diseases].

PMID- 9190544
TI  - [Klippel-Trenaunay-type congenital angiodysplasia syndrome; medical and
      psychological aspects].

PMID- 9190545
TI  - [A patient with an unexplained low level of high-density-lipoprotein
      cholesterol].

PMID- 9190546
TI  - [Clinical judgement and decision making in clinical practice. A free spirit with
      imminent paraplegia].

PMID- 9190547
TI  - [The antecedents of the 1876 Legislation No. XIV: The Hungarian Council of Public
      Health (1868), the Hungarian Society for Public Health (1886) and the Judiciary
      Medical Council (1890)].

PMID- 9190548
TI  - [Black bile. Development of a concept in medical history from antiquity to modern
      times].

PMID- 9190549
TI  - [Kaposi sarcoma-associated herpesvirus; human herpesvirus 8].
AB  - The discovery of a new human herpesvirus in Kaposi's sarcoma tissues of AIDS
      patients has opened up new facts in virology and oncology. This herpesvirus was
      first descriptively named Kaposi's sarcoma-associated herpesvirus, but was
      recently renamed human herpesvirus 8. Human herpesvirus 8 DNA has been
      consequently found in all forms of Kaposi's sarcoma, suggesting that it might be
      involved in the pathogenesis of the disease. Additionally, human herpesvirus 8
      can be detected in both malignant and benign lymphoproliferative diseases, such
      as body-cavity-based B-cell lymphomas and multicentric Castleman disease. The
      virus was also recently found in rare vascular tumors in patients with
      angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia.
      Although only a limited portion of the viral DNA has been sequenced, it has
      become evident that the new herpesvirus is equipped with genes that could confer
      oncogenic potential. The virus can now be cultured, providing the possibility for
      studies of viral replication and the mode of transmission, and also for the
      development of serologic tests.

PMID- 9190550
TI  - [Immune responses of IgG, IgA and anti-CagA IgG to Helicobacter pylori in
      dyspeptic and peptic ulcer patients].
AB  - The anti-H. pylori IgG, IgA, and anti CagA responses in dyspeptic patients have
      been evaluated. Of 481 patients 76% tested positive for IgG anti-H. pylori, 57%
      for anti-CagA, and 52% IgA for anti H. pylori. There was a significant age
      related increase in IgG anti-H. pylori and IgA anti-H. Pylori prevalence, whereas
      anti-CagA positives were unreliable in this respect. The IgG seropositivity was
      the highest (93%) in duodenal ulcers (DU), 82% in antral gastritis and/or
      bulbitis (AG +/- /B), and 71% in gastric ulcer (GU). GU patients compared with DU
      and AG +/- /B ones tended to have the highest IgA anti-H. pylori prevalence (78%
      vs. 66% and 61%). The anti-CagA seropositivity was the most pronounced (80%) in
      DU followed by GU (72%) and AG +/- /B (68%). It is suggested that the
      serodiagnosis including IgG, IgA anti-H. pylori and anti-CagA determinations can
      not replace endoscopy in revealing the exact nature of gastroduodenal lesions.
      IgA anti-H. pylori determination in female patients with GU can be a valuable
      diagnostic tool. It is stated that in Hungary the prevalence of CagA positive H.
      pylori strains in anti-H. pylori IgG positive dyspeptic patients is 85%.

PMID- 9190551
TI  - [Pleomorphic xanthoastrocytoma].
AB  - Pleomorphic xantho-astrocytoma (PXA) is a relatively rare brain tumor of
      adolescents and young adults characterized by its superficial location with
      frequent involvement of the meninges, and its slow growth despite features of
      histological atypia. The authors present a retrospective immunohistochemical
      analysis of 8 surgically treated cases in order to determine the expression of
      glial and neuronal markers, and to assess the proliferating cell fraction. The
      study population comprised 1 female and 7 male patients with a mean age of 26.7
      years, most tumors being located in one of the temporal lobes. Epilepsy
      predominated as a presenting symptom. Five cases were assigned WHO graded II,
      while the diagnosis of anaplasia (WHO grade III) was established in three, based
      either on elevated mitotic counts or the presence of necrosis. Immunostaining
      with the proliferation marker MIB-1 was present in 2.05% of cells in the former
      groups, while 4.66% showed labeling in the latter. Postoperative follow-up
      averaged 6.7 years, with only one recurrence of an anaplastic tumor. All tumors
      expressed some amount of glial fibrillary acidic protein and were shown to
      elaborate a characteristic pericellular reticulin network. There was focal
      reactivity for alpha-1-antitrypsin, but neither the monocyte-macrophage
      associated antigen CD68 nor lysozym could be detected in neoplastic cells. In 7
      cases, scattered individual tumor cells exhibited synaptophysin positivity. The
      authors review problems and prognostic issues of the histologic diagnosis of
      anaplasia occurring in some 20% of the cases. A possible dysontogenic origin of
      PXA and its nosologic relationship to the so-called desmoplastic neuroepithelial
      tumors of infancy are discussed. This is the first study of pleomorphic
      xanthoastrocytoma in the Hungarian literature.

PMID- 9190552
TI  - [Experience with the first thousand cases of short-term postpartum hospital stay
      in Hungary].
AB  - There is an international trend shortening postpartum hospital stay. While less
      than 2 days care initiated harsh response in the USA, questions and anxiety were
      provoked here by reducing puerperal hospital stay from 5-7 to 2 days. Thousand
      cases out of 7,277 deliveries were discharged early following appropriate
      education and normal pregnancy. Response from the affected patients and local
      doctors are discussed. Maternal and neonatal readmission rate call for careful
      decision making concerning early discharge. Social motivation has to enjoy
      priority over economic measures.

PMID- 9190554
TI  - Simplified treatment of acute staphylococcal osteomyelitis of childhood. The
      Finnish Study Group.
AB  - OBJECTIVE: Recommendations on treatment of acute staphylococcal osteomyelitis of
      children, based mostly on retrospective analyses, comprise surgical drainage, up
      to 6 weeks fo antimicrobials guided by the erythrocyte sedimentation rate, and
      the possibility of switching to the oral route only if monitoring of serum
      bactericidal titer is guaranteed. A prospective study was conducted to test
      whether the treatment could be simplified. DESIGN: Fifty pediatric cases of acute
      Staphylococcus aureus osteomyelitis were randomized to receive 150 mg/kg/day of
      cephradine divided in four doses, or 40 mg/kg/day in four doses of clindamycin.
      The treatment was initiated intravenously, but switched to oral administration
      mostly within 4 days, using the same doses. The peak antimicrobial serum
      inhibitory titer or bactericidal titer was not measured. The course of illness
      was monitored by blood leukocytes, erythrocyte sedimentation rate, and serum C
      reactive protein. The follow-up was extended to 1 year posthospitalization.
      SETTING: Eight tertiary pediatric-orthopedic hospitals in Finland. MAIN OUTCOME
      MEASURE: Full recovery and remaining healthy at least 12 months from hospital
      discharge. RESULTS: The lower and upper extremities were affected in 72% and 8%
      of patients, respectively. No surgery at all or needle aspiration only was
      performed in 62% and drilling in 38%. C-reactive protein and the sedimentation
      rate normalized within 9 days and 29 days, respectively. X-ray changes developed
      in 68% but had no prognostic significance. The mean hospitalization time was 11
      days, and the total duration of antimicrobials was 23 days. No failure has
      occurred nor have long-term sequelae been observed in any patient. CONCLUSIONS:
      Treatment of pediatric acute staphylococcal osteomyelitis can be simplified and
      costs reduced by keeping surgery at a minimum, shortening hospitalization and the
      course of antimicrobials, switching quickly to the oral route, and not monitoring
      serum bactericidal activity.

PMID- 9190553
TI  - Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital
      diaphragmatic hernia. The Neonatal Inhaled Nitric Oxide Study Group (NINOS).
AB  - OBJECTIVE: We designed and conducted a randomized, double-masked, controlled
      multicenter study to determine whether inhaled nitric oxide (INO) in term and
      near-term infants with congenital diaphragmatic hernia (CDH) would reduce the
      occurrence of death and/or the initiation of extracorporeal membrane oxygenation
      (ECMO). PATIENTS AND METHODS: Infants of 34 weeks gestation or more, <14 days of
      age with CDH, without known structural heart disease, requiring assisted
      ventilation for hypoxemic respiratory failure with two oxygenation indices (OIs)
      of 25 or more at least 15 minutes apart, were eligible for this trial. Infants
      were centrally randomized and then received masked treatment with 20 ppm NO or
      100% oxygen as control. Infants with less than a full response to 20 ppm NO
      (increase in PaO2 > 20 Torr) after 30 minutes were evaluated at 80 ppm NO/control
      study gas. RESULTS: The 28 control and 25 treated infants enrolled by the 13
      participating centers were not significantly different at randomization for any
      of the measured variables including prerandomization therapies and initial OIs
      (45.8 +/- 16.3 for controls, 44.5 +/- 14.5 for INO). Death at <120 days of age or
      the need for ECMO occurred in 82% of control infants compared with 96% of INO
      infants (ns). Death occurred in 43% of controls and 48% of the INO group (ns),
      and ECMO treatment was used for 54% of control and 80% of INO-treated infants.
      There was no significant improvement in PaO2 (delta PaO2 7.8 +/- 19.8 vs 1.1 +/-
      7.6 Torr, ns) nor significant reduction in OI (-2.7 +/- 23.4 vs 4.0 +/- 14.8, ns)
      associated with INO treatment. Mean peak nitrogen dioxide (NO2) concentration was
      1.9 +/- 1.3 ppm and the mean peak methemoglobin was 1.6 +/- 0.8 mg/dL. No infant
      had study gas discontinued for toxicity. There were no differences between the
      control and INO groups for the occurrence of intracranial hemorrhage, specific
      grades of intracranial hemorrhage, periventricular leukomalacia, brain
      infarction, and pulmonary or gastrointestinal hemorrhages. CONCLUSIONS: Although
      the immediate short-term improvements in oxygenation seen in some treated infants
      may be of benefit in stabilizing responding infants for transport and initiation
      of ECMO, we conclude that for term and near-term infants with CDH and hypoxemic
      respiratory failure unresponsive to conventional therapy, inhaled NO therapy as
      used in this trial did not reduce the need for ECMO or death.

PMID- 9190555
TI  - Adolescents and anabolic steroids: a subject review. American Academy of
      Pediatrics. Committee on Sports Medicine and Fitness.

PMID- 9190556
TI  - Evaluation and medical treatment of the HIV-exposed infant. American Academy of
      Pediatrics. Committee on Pediatric AIDS.
AB  - As a result of the expanding human immunodeficiency virus (HIV) infection
      epidemic and recently published recommendations for routine HIV testing with
      consent for all pregnant women in the United States, pediatricians are becoming
      increasingly involved in providing care to infants born to HIV-infected women.
      This article provides guidelines about counseling the parent or care giver of the
      infant, use of antiretroviral therapy to reduce the risk of infection in the
      infant, medical treatment of the HIV-exposed infant, laboratory testing to
      determine the infection status of the infant, laboratory monitoring of
      hematologic and immunologic parameters, prophylaxis for Pneumocystis carinii
      pneumonia, and recommendations for immunizations and tuberculosis screening.

PMID- 9190558
TI  - Echocardiography in infants and children. American Academy of Pediatrics. Section
      on Cardiology.

PMID- 9190557
TI  - Use of codeine- and dextromethorphan-containing cough remedies in children.
      American Academy of Pediatrics. Committee on Drugs.
AB  - Numerous prescription and nonprescription medications are currently available for
      suppression of cough, a common symptom in children. Because adverse effects and
      overdosage associated with the administration of cough and cold preparations in
      children have been reported, education of patients and parents about the lack of
      proven antitussive effects and the potential risks of these products is needed.

PMID- 9190559
TI  - Medication for children with attention disorders.

PMID- 9190560
TI  - Central opiate receptor blockade by naloxone impairs thalamic and hypothalamic
      autoregulation in the cat.
AB  - Experiments were carried out in order to determine the effects of centrally
      induced opiate receptor blockade on the autoregulation of the regional cerebral
      blood flow (rCBF, measured by the H2-gas clearance technique) of the
      anesthetized, ventilated cats. General opiate receptor blockade was induced by
      intracerebroventricularly (i.c.v) injected naloxone. Changes of teh lower limit
      of hypothalamic, thalamic and white matter blood flow autoregulation were studied
      by reducing the systemic mean arterial pressure (MAP) in a stepwise manner to 80
      mmHg, 60 mmHg and 70 mmHg by hemorrhage. Centrally administered naloxone (10
      microg/10 microl/kg, i.c.v) resulted in an abolishment of the autoregulatory
      mechanisms in the hypothalamic and thalamic regions but caused no such changes in
      the white matter. These observations suggest that 1.) intracerebral opiate
      receptors and/or central opioid peptiderg mechanisms play a significant role in
      the maintenance of the thalamic and hypothalamic blood flow autoregulation during
      hemorrhagic hypotension and 2.) the involvement of the endogenous opioid peptide
      system in rCBF autoregulatory mechanisms is regionally different.

PMID- 9190561
TI  - (R)-methanandamide inhibits receptor-induced calcium responses by depleting
      internal calcium stores in cultured astrocytes.
AB  - The effect of (R)-methandamide, a chiral analog of the endogenous cannabimimetic
      anandamide, was investigated on calcium signalling in cultured rat astrocytes
      loaded with Indo-1. Pretreatment of astrocytes with (R)-methandamide resulted in
      the inhibition of calcium responses induced by endothelin-1 or glutamate. Test of
      the filling level of internal calcium stores and biochemical assays of
      phospholipase C activity suggested that this inhibition resulted from the
      depletion of internal pools. This effect occurred in a reversible time- and dose
      dependent manner, and was prevented by treating the cells with pertussis toxin
      (PTX) but was not reproduced by similar concentrations of arachidonic acid.
      Altogether, these observations demonstrate that this stable analog of anandamide
      controls calcium signalling in astrocytes through a PTX-sensitive mechanism which
      leads to the depletion of fast mobilizable internal stores.

PMID- 9190563
TI  - [Standardization of back treatment].

PMID- 9190562
TI  - Intracellular Ca2+ distribution in migrating transformed epithelial cells.
AB  - Migration of transformed Madin-Darby canine kidney (MDCK-F) cells depends on the
      polarized activity of a Ca2+-sensitive K+ channel. We tested whether a gradient
      of intracellular Ca2+-concentration ([Ca2+]i) underlies the horizontal
      polarization of K+ channel activity. [Ca2+]i was measured with the fluorescent
      dye fura-2/AM. Spatial analysis of [Ca2+]i indicated that a horizontal gradient
      exists, with [Ca2+]i being higher in the cell body than in the lamellipodium.
      Resting and maximal levels during oscillations of [Ca2+]i in the cell body were
      found to be 135 +/- 34 and 405 +/- 59 nml/l, respectively, whereas they were 79
      +/- 18 and 307 +/- 102 nmol/l in the lamellipodium. This gradient can partially
      explain the preferential activation of K+ channels in the plasma membrane of the
      cell body. We applied a local superfusion technique during migration experiments
      and measurements of [Ca2+]i to test whether its maintenance is due to an uneven
      distribution of Ca2+ influx into migrating MDCK-F cells. Locally superfusing the
      cell body of migrating MDCK-F cells with La3+ alone or together with
      charybdotoxin, a specific blocker of Ca2+-sensitive K+ channels, slowed migration
      to 47 +/- 10% and 9 +/- 5% of control, respectively. Local blockade of Ca2+
      influx into the cell body and the lamellipodium with la3+ was followed by a
      decrease of [Ca2+]i at both cell poles. This points to Ca2+ influx occurring over
      the entire cell surface. This conclusion was confirmed by locally superfusing
      Mn2+ over the cell body and the lamellipodium. Fura-2 fluorescence was quenched
      in both areas, the decrease of fluorescence being two to three times faster in
      the cell body than in the lamellipodium. However, this difference is insufficient
      to account for the observed gradient of [Ca2+]i. We hypothesize that the
      polarized distribution of intracellular Ca2+ stores contributes significantly to
      the generation of a gradient of [Ca2+]i.

PMID- 9190564
TI  - [Surgery of lumbar disk prolapse in Scandinavia. A questionnaire study in
      Scandinavian neurosurgical departments in 1993].
AB  - This article consists in a review of treatment for lumbar disc prolapse in 1993,
      as reported by all 22 neurosurgery units in the Nordic countries, serving a total
      population of 23.5 million. Of surgical operations for the condition, 37 per cent
      were performed by neurosurgeons-using standard lumbar discectomy in 61.3 per cent
      of cases, microsurgical techniques in 36 per cent of cases, and percutaneous
      lumbar discectomy in the remaining 2.7 per cent. Chemonucleolysis is no longer
      considered a viable therapeutic alternative. In the Nordic countries as a whole,
      the annual incidence of lumbar disc prolapse surgery is 52.5 per 100,000, though
      the figure varies from one country to another.

PMID- 9190565
TI  - [Dyspepsia treatment program needs scientific assessment].

PMID- 9190566
TI  - [Laser treatment of benign prostatic hyperplasia].
AB  - Transurethral resection of the prostate (TURP) has been the gold standard for BPH
      for over 50 years. For the last five years laser treatment of BPH has been
      developed as a new modality. The principles of laser surgery and the options
      available in clinical practice today are outlined. A survey of indications,
      patient selection, results and complications are given based on the authors' own
      experience and reports from the international literature.

PMID- 9190567
TI  - [Windows of opportunity].

PMID- 9190568
TI  - [Qualitative methods in empirical health research. III. The individual in-depth
      interview].
AB  - This third article in this series provides a review of various qualitative
      research methods which are appropriate to the health care setting. The in-depth
      interview is distinguished from other forms of interview, and practical aspects
      of its application, such as preparation, setting, context, and recording are
      discussed in detail.

PMID- 9190569
TI  - [Retinal calcium-binding proteins--their function and pathology].
AB  - Calcium is involved in most cellular processes through calcium-binding proteins,
      belonging to the EF-hand superfamily. Recently new members of this family were
      found in the retina of vertebrates. Functions of these proteins and their
      relations to some neurological diseases are reviewed. Other EF-hand proteins
      found in the retina are also described.

PMID- 9190570
TI  - [Metabolism of nicotine--mechanism and clinical effects of toxicity].
AB  - Nicotine is a major constituent of tobacco and exerts a number of physiological
      effects. Metabolism of nicotine in animal and human tissues is reviewed. Clinical
      considerations regarding the problems of toxic effects of nicotine in human and
      molecular basis of carcinogen mechanism of nicotine derivatives are discussed.

PMID- 9190571
TI  - [Allergic inflammation--participation and role of adhesion molecules].
AB  - Adhesion molecules (AMs) are one of the main research areas in biology, cytology
      and medicine. During last years a great number of AMs was discovered and employed
      in several mechanisms, including inflammation. Bronchial asthma, allergic
      rhinitis and conjunctivitis are considered as inflammatory disorders. Based on
      both in vitro and in vivo studies several mechanisms of selective recruitment
      eosinophils and basophils through AMs have been developed. Moreover, cytocines,
      biological peptides and other mediators play role in expression and function of
      adhesion molecules. Although several aspects of these processes still remains
      unclear, in vivo data (from animal and human experiments) document the existing
      of some of these mechanisms. Additional studies, including the use of adhesion
      molecule antagonists, will clarify the importance of leukocyte adhesion in the
      pathophysiology of allergic diseases. This review article describes
      characteristics, properties, regulation of expression and the role of leukocyte
      endothelial adhesion molecules in pathogenesis of allergic diseases.

PMID- 9190572
TI  - [Calcium deficiency as on of the risk factors of osteoporosis].
AB  - An adequate calcium intake is important to attain peak bone mass and to oppose
      that component of age-related bone loss. Calcium deficiency is one of the risk
      factors for osteoporosis. Calcium supplements is particularly important for
      preventing bone loss and fractures.

PMID- 9190573
TI  - [Progress in diagnosis of infections brought on by Helicobacter pylori].
AB  - A wide range of techniques was developed for identification of Helicobacter
      pylori, since the association of the microorganism with gastritis and peptic
      ulcer has been established in 1983. Up to now, isolation and identification of H.
      pylori from the gastric biopsy, remains the standard diagnostic procedure.
      However, attention is focused on rapid non-invasive tests, for monitoring the
      infection, such as urea breath test. Serological methods as ELISA and Western
      blot are suitable for estimation of specific anti-H. pylori local and systemic
      humoral response. Molecular tests based on PCR reaction allow the detection of H.
      pylori in biopsy specimens and recently in other clinical samples as saliva or
      faeces. They are also very promising in epidemiological studies.

PMID- 9190574
TI  - [Selenium in the cytotoxicity of cisplatin].
AB  - Cisplatin is a widely used chemotherapeutic agent, highly effective in the
      treatment of various types of human malignancies. The antitumor activity of
      cisplatin is attributed mainly to its ability to form adducts with DNA. Cisplatin
      may react with proteins and also with glutathione forming complex GS-Pt. This
      agent causes haematological, neurological toxicity and changes function of
      different cells. Recently, is has been reported that administration of sodium
      selenite reduces cisplatin toxicity without inhibiting the antitumour activity of
      cisplatin. This review focuses on the mechanism of cisplatin-induced cytotoxicity
      and the protective role of selenium.

PMID- 9190575
TI  - [The phenomenon of aggressive behavior and potential violence in children and
      adolescents].

PMID- 9190576
TI  - [Childhood and violence: perpetrator and victim perspectives from the viewpoint
      of criminology].
AB  - Police crime statistics show a significant increase in the rates of violent
      crimes committed by children during the last two years. However, since in Germany
      children under the age of 14 are not accountable for criminal offences, these
      statistics are highly selective. On the other hand, police crime statistics also
      show a huge increase of violent crimes committed by juveniles and young adults
      which cannot be explained by changes of police intervention strategies. It seems
      reasonable to attribute this mainly to changed living conditions of young people,
      particularly the increase proportion of children and adolescents living below the
      thresholds of poverty. To put the issue of violence and children in perspective,
      the victimization of children should not be overlooked. Criminological as well as
      psychological research show the devastating consequences of physical and sexual
      abuse experiences during childhood. Results of a representative german survey
      concerning the prevalence of violent victimization experiences during childhood
      are presented. 13.5% of the male and 16.1% of the female respondents had been
      victims of severe physical or sexual abuse during childhood. If repeatedly
      witnessing parental violence is additionally taken into consideration, these
      rates are 18.3% for male and 20.5% for female respondents. A comparison of age
      groups failed to identify significant differences of victimization rates, except
      the rates of minor violence committed by parents. Thus it can be assumed
      tentatively, that the proportion of children subjected to severe violent acts
      committed by closely related adults as well as the rate of those witnessing
      parental violence has remained constant over time.

PMID- 9190577
TI  - [Aggression and violence in children in different contexts].
AB  - Starting with the hypothesis that children's aggressive and potentially violent
      behavior is the climax of escalating conflicts that cannot be expressed or showed
      in any other way, we analyse, in the following article, the conditions from which
      these behavior pattern arise. We have focused on the following areas; the
      individual, the family, the school and society, and we have tried to show how the
      development of children's aggressive behavior is determined by the problem
      constellations in these different contexts. Insecure and disorganised early
      bonding experiences and/or dysfunctional family relationship patterns combined
      with parental upbringing methods that support or condone aggressive behavior, can
      lead to children having fewer resources or social skills available than their
      peers in kindergarten and school. This may result in conflict and lack of social
      integration in these institutions.

PMID- 9190578
TI  - [Violence in the school--analysis of the problem and possible interventions].
AB  - This article deals with a topic being controversially discussed in public for
      several years now: violence in school. Following the outlining of the current
      state of research and the naming of causes is a representation of the research
      project "Violence in School' sponsored by the German Research Community (Deutsche
      Forschungsgemeinschaft, DFG). This four-stage program which was designed to
      analyze and prevent violence in school has set itself the aim to get a
      comprehensive idea of extent and appearance of violent behavior as well as to
      find condition-constellations in the school environment and also externally.
      Finally, some ideas for prevention and intervention of violence in school are
      given. Those recommendations represent a set of proposals that can be found in
      the bibliography.

PMID- 9190579
TI  - [Management of violent acts within the scope of a pedagogic concept of self and
      social development--or: talking with school children about violence].
AB  - In order to deal with physical aggression in schools it is necessary to develop
      an educational concept in which the teachers parallel to their observations of
      the subject orientated learn-track include the relationship- and the self
      development-track (three-track-education). In this concept of classifying dialogs
      which follow the conflict situations have equal importance to other events during
      school-lessons. The dialogs take place parallel to the lessons. This method
      requires a flexible organisation of the lessons in which the pupils are used to
      work on their own. An extension of the teachers competence is necessary. The
      extension of competence is related to a close observation of social events and to
      a development of models to explain the problematic behavior of pupils. If it
      becomes possible for example to interpret part of the pupils' behavior as scenic
      acting this new point of view may lead to new solutions. The educational concept
      is orientated on a model of psychoanalytical explanation in which the current
      situation stands in the foreground. The problem which thus becomes apparent can
      be now be handled by reconstructing the exterior events (interactions) and by the
      symbolic presentation of the interior perception (annoyance, anger, rage). Thus
      the pupils learn to deal with their inner turbulences in the constructive manner.
      For the acting in the public forms of making amends are practised. Physical
      aweness and fitness is seen as an important base for self- and social processes.
      The work of a man within a boys' group and of a woman within a girls' group
      offers the possibility of sexual identity.

PMID- 9190580
TI  - [Decreasing violence in the school: study of a cooperative intervention].
AB  - Can physically aggressive behavior among pupils be reduced by some easily
      applicable interventions? The teaching staffs of four elementary schools were
      advised (1) to hold regular classroom meetings (on rules of behavior, helping
      attacked peers etc), (2) to stop acute aggressive behavior and encourage positive
      behavior, and (3) to change some situational factors (especially during break
      time). Preliminary results suggest that a highly committed staff can reduce
      aggressive behavior by these interventions. Further study is needed, however, as
      to the contribution of individual measures and the extent and stability of the
      effects to be obtained.

PMID- 9190581
TI  - [Aggression, inanimate objects and fantasy of invulnerability].
AB  - Some highly aggressive children prefer to symbolize and express their inner
      experiences by toys, which represent "things" and not living creatures. The
      special function of this preference represents a defense structure of deanimation
      after traumatization. It implicates the phantasy, that inanimated objects are not
      part of the vivid dialogue and can "survive" every attack. Thus in the
      transferential relationship the deanimation can slowly be reanimated by borrowing
      the undestroyable aspects of a thing in combination with the suffering feelings
      of the therapist.

PMID- 9190582
TI  - [Systemic counseling in dyssocial behavior, delinquency and violence].
AB  - The article summarizes characteristic interactive patterns in social systems
      concerned with acting-out, delinquent and violent behavior in adolescents. As a
      consequence, it develops a multi systems consultation approach. Core features of
      such an approach are the clarification of service demands and of available
      resources, the development of new and sometimes unusual cooperation, positive
      connotation of distrust and chaos, and an intelligent questioning of the
      usefulness of ones owen professional activities. At the end the question is
      raised, whether and in which ways educators, physicians and psychologists could
      involve themselves in political decision processes about media, work and welfare
      legislation, which influence their adolescent clients life situation.

PMID- 9190583
TI  - [Behavior therapy with aggressive children].
AB  - Modern behavior therapy strategies which reduce aggressive behavior are based on
      developmental psychopathological assessments. These help to confirm intervention
      steps adapted to each specific age group. The extensive spectrum of methods in
      child behavior therapy offers different cognitive and social elements which are
      used to help the child effectively. The training for aggressive children by
      PeTERMANN and PeTERMANN (1994) which generally includes behavior-oriented family
      counselling shall be considered.

PMID- 9190584
TI  - [FAUSTLOS--a curriculum for promoting social competence and preventing aggressive
      and violent behavior in children].
AB  - FAUSTLOS is a curriculum that has been developed for the prevention of aggression
      and potentially violent behavior in children in nursery and primary school. A
      lack of social skills is regarded as one of the fundamental causes that
      deteriorates problem and conflict solving. FAUSTLOS is the German version of an
      American program called Second Step that has been developed by the Committee for
      Children in Seattle and has been successfully put into practice in several
      American states over the last eight years. The project "Kinder und Gewalt" has
      adapted it for the German speaking countries. FAUSTLOS is at present in its pilot
      phase. The following is a general survey of the inception, contents and methods
      of the curriculum and the planning and execution of the pilot phase.

PMID- 9190585
TI  - [The toxicological characteristics of Gastrofenzin. IV. Its gonadotropic action].
AB  - An evaluation of the gonadotropic effect of Gastrofenzin has been carried out in
      conditions of 45-day and 90-day oral application (daily, 5 times per week) in
      male white rats. The experiments are performed in doses 1/20, 1/100 and 1/200
      LD50, respectively 33.8, 6.7 and 3.4 mg.kg-1. Functional and morphologic methods
      of investigation have been used-count, character and mobility, acid and osmotic
      resistance of the sperm cells, mean number of sperm cells in the sperm tube,
      spermatogenesis' indices, morphological characteristic of the testes as well as
      autoradiographic method for determining the proteolytic activity of the acrosome.
      Irrespective of the application term the highest dose (33.8 mg.kg-1) causes
      systemic deviations in the functional indicators and physiologic fluctuation of
      the morphologic parameters characterizing the spermatogenic epithelium at
      preserved proteolytic activity of the acrosome. The dose 1/20 LD50 (33.8 mg.kg-1)
      is considered to be effective on the gonads in conditions of three-month chronic
      oral application of Gastrofensin and the threshold of the gonadotoxic activity is
      about 1/100 LD50-6.7 mg.kg-1.

PMID- 9190587
TI  - [A chemical hygiene assessment of point emitters and of an unorganized source of
      air pollution from copper smelting at Nipkitoks in the city of Pernik].
AB  - Concentrations of adverse substances in air emissions of a copper manufacture
      have been determined. There have been found out dust, soot, copper, tin, lead.
      The generated emissions of these toxic elements from the investigated point
      generator are not above the admissible ranges and the established technologic
      conditions are not problematic. The concentrations of vinilchloride, carbon
      monoxide and carbon dioxide in the air of the working environment are below the
      respective admissible concentrations and the manufacture is not a source of
      pollution for the environment.

PMID- 9190586
TI  - [The dust factor of the work and adjacent environments in the working of
      manganese ore].
AB  - The dust professional exposition of the above ground workers in the mines
      "Obrochishte" at the village of Tsurkva, Varna Province has been evaluated as
      well as the dust pollution in the atmosphere of the village in respect to the
      hygienic standards for quartz-containing sand and manganic aerosol. The results
      show that the pollution with quartz-containing dust is in the normal ranges
      according to all hygienic parameters for fibrogenic dusts in working environment
      and the workers are not exposed to risk of silicosis. A greater than the standard
      exposition to manganic aerosol (from 1.1 to 5 PDK) has been found out in some
      groups of workers in the ore-dressing plant, in truck drivers of the intra-fabric
      transport, in fadromists and heavy scraper workers. The manganic aerosol is found
      to be a pollutant of the atmosphere also, and the cause of this is thought to be
      the mine storages in the open-air and the poor state of the intra-fabric roads.

PMID- 9190588
TI  - [A membrane filter sampling method for determining microbial air pollution].
AB  - The method is a contribution in the evaluation of the exposition and the control
      of the standards for organic powders. The method concerns the sample-taking
      procedure and the analysis-making technique for determining of the concentration
      of the microbial pollution of the air. It is based on filtering of some amount of
      air through a membrane filter which is then processed for cultivating of
      microbial colonies on its surface. The results are obtained in number of
      microbial colonies per unit of air. The method presents opportunity to select and
      vary the filtered volume of air, to determine the respirable fraction, to
      determine the personal exposition, as well as for the simultaneous determining of
      the microbial pollution together with other important parameters of the particle
      pollutants of the air (metal, fibre and others).

PMID- 9190590
TI  - [A health status study of the population subjected to combined exposures to
      ionizing and nonionizing radiation factors].
AB  - The values of the dose effective extrinsic and intrinsic radiation of humans in
      the regions near to urane mines and urane plants in Bulgaria are pointed out.
      Some aspects of investigation of the health and risk evaluation of the population
      and of the former workers are reviewed.

PMID- 9190589
TI  - [Changes in the humoral immune response in occupational exposure to metal
      aerosols].
AB  - The object of the study is to screen the state of the humoral immune response in
      the workers at the chemical plan Khimko AD-Vratsa who are in professional contact
      with metal aerosols, containing Cr, Ni, Cu, Fe, Zn, Mn, Al, nitric oxides,
      ammonia, carbon oxide and dust. 60 workers have been covered (exposed group) with
      working experience of 9.89 +/- 4.07 years and the control group consisted of 60
      persons from the same region working at two other plants. A comparatively high
      rate was established of infections of the upper respiratory ways (rhinitis,
      laryngitis, chronic bronchitis, rhinopharyngitis and conjunctivitis) in the both
      groups: in the exposed group-in 12 persons (20%) and in the control group-in 5
      (8.3%) persons. The study of the humoral immune response showed activated immune
      defence, expressed in increasing of the serum IgG and IgA (18.56 +/- 4.79 g/l and
      3.64 +/- 1.32 g/l respectively) and of C3-fraction of the complement (1.14 +/-
      0.25 g/l) in comparison to the control group 0.96 +/- 0.21 g/l, p < 0.00003). In
      32 (53%) exposed workers an increased values of serum IgG have been found out.
      This rate is considerably higher than the one of the control group (33%, p <
      0.05). An increased level of HBsAg-11.7% (7/60) and 8.3% (5/60), respectively in
      the exposed and control groups is reported. The authors have not found convincing
      evidence for autoimmune response in the exposed group of workers. These facts can
      be hardly interpreted at this stage as trace reaction resulting from frequent
      infections. It is possible that this activation of the humoral immunity is
      related to the environment-polluting metal aerosols which influence the immune
      system.

PMID- 9190591
TI  - [Psychosocial factors in the family environment of chronic patients and of
      healthy pupils of elementary school age].
AB  - The performed inquiry covers 376 primary school-aged children from whom 103--with
      chronic diseases and 273--healthy. Some psychological and social factors which
      could influence adversely the health state of the children, like single parent,
      bad relations between the parents and between parents and children, etc. have
      been studied. The data reveal unfavourable tendency in respect to adaptation
      abilities of children with chronic diseases.

PMID- 9190592
TI  - [The communal hygiene problems of hospital institutions].
AB  - The study covers 17 hospitals on the territory of the Capital Community,
      including their clinics, departments and rooms for treating of social significant
      and other diseases. The analysis reveals a number of negative aspects:
      inappropriate situation, insufficiency or lack of green areas, unfavourable
      aspect of the rooms, overcrowding, insufficient area of the windows, irrational
      heating regime, lack of ventilation regime, etc. Undesirable parameters of the
      microclimate are observed in the patients' rooms and this leads to discomfort to
      the patients and prolonging of the convalescent period. A study on a large scale
      for the town of Sofia is presented which aims at revision of the current building
      norms and requirements in respect of their correction and the improving the
      future building of hospitals in our country.

PMID- 9190593
TI  - [The physical capacity of Bulgarian boys from homes for children and youth].
AB  - The educational effects and living conditions' impact on the physical activity of
      boys with unequal social status have been investigated. Children from under
      school age to secondary school age, living in different towns and regions of the
      country have been studied. The indicators used for physical activity are 60
      meters sprint, long jump, right and left hand small ball throw. A comprehensive
      analysis of the studied indicators is made. It has been found out that the boys
      from the asylums aged from 3 to 6 years living in town have significantly poorer
      results in the sprint events compared to the mean standards for the age.

PMID- 9190594
TI  - [A method for studying the dynamic mental work capacity of pupils from upper
      grades].
AB  - The presented methods include mechanical studies of the changes in the vision
      movement reaction, the stability of the attention and mental activity; subjective
      evaluation of the tiredness, self-esteem, activity and temper as well as of some
      individual features. The methods have been approbated on students at XI, XII
      grade of SOU and present possibilities for evaluation of the correspondence
      between strain and physiologic and psychologic changes in the students during
      training.

PMID- 9190595
TI  - [The microclimate conditions of the environment for treating patients in hospital
      clinics and wards (a review)].
AB  - The problem of the microclimatic parameters of the environment in some clinics
      and hospital departments is discussed as well as their significance in the
      general therapeutic course. The impact of the air environment as a potent
      therapeutic factor is outlined. It is stated that the temperature regime in the
      rooms must be differentiated in accordance to the climatic conditions, seasons,
      patient's age, the nosologic group. Discussing the problem with regard to the
      balance "man-environment" it is outlined that the adaptive capabilities, which
      are narrowed and altered in the patient, can not compensate for the unfavourable
      conditions of the environment. The authors point at differentiated values of the
      microclimatic parameters for the rooms in some clinics and departments.

PMID- 9190596
TI  - [The effect of the factors of the working and living environment on
      oxidative/antioxidative balance (a review)].
AB  - Because of the high reactivity of the free oxygen radicals the maintaining of a
      certain balance between the activity of the antioxidative system and the level of
      the free radicals is of great importance for the health of man. Literary data are
      reviewed concerning the shifting of this balance towards oxidants' excess due to
      many factors like ionizing radiation, hyperoxia, toxic noxae, considerable
      physical overstrain, overcooling, stress and others. The antioxidative and pro
      oxidative food composition is of special importance for maintaining of the
      oxidative/antioxidative balance of the organism. The nutrition regiment could
      mould the toxicity of some of the mentioned agents.

PMID- 9190597
TI  - [A national plan for action on the environment and health].
AB  - Preserving the environment and human health is an irreversible part of the
      activity towards stable development. Acknowledging the necessity of such
      development, the European countries commence working out of plans that
      subordinate their policy to this object. Concerning the health policy the new
      strategy requires improving of the integrated system for environmental and health
      control-an administrative framework that reflects the partnership between health
      and environmental institutions and the other sectors at all levels of control.
      The main means and instruments for control of health and the environment are: 1)
      information system for health and environment; 2) identification and evaluation
      of the health and environmental risks; 3) a framework of the current legislation;
      4) additional measures for control, including economical and fiscal instruments;
      5) professional training and qualification; 6) public information and health
      education; 7) public participation; 8) researches and technological works. The
      correct functioning of the complex "taking decisions-control system" and the
      expected results depend on the adequate working out and application of the above
      mentioned means. The national action plan for environment and health is a
      fundamental project on a large scale for preserving the health and environmental
      interests of the country targeting at its stable progress.

PMID- 9190598
TI  - [The hygienic ergonomic protection of speech communication over time].
AB  - In the course of the experimental laboratory studies it was found out a
      significant impairment of the communication following a 2-hour processing of
      speech signals in conditions of masking noise. In order to diminish the auditory
      exhaustion in impeded communication the authors created physiologically grounded
      model of the working and resting regime in accordance to the experimental data,
      which require the including of two breaks in the first half of the working day,
      i.e. after a two hour exposition to masking noise. The minimal duration of the
      break at the end of the second hour (according to the experimental data) must be
      not less than 10 minutes in order to reach the initial or near to it speech
      communication. The time of the second break may coincide with the regulated lunch
      time. The created working and resting regime was approbated in working conditions
      at DF "Kremikovtsi". It was found out that following the introduction of the
      physiological regime of work and rest, the auditory exhaustion decreased which
      was expressed in lowering of the rate of tone-intensity steps.

PMID- 9190599
TI  - [Regulative music therapy and training as a means for enhancing adaptive
      potentials and for overcoming fatigue and stress].
AB  - The method of regulative music therapy (RMT) by C. Schwabe is presented-its
      mechanisms, the caring out procedure, usability and application domains. RMT can
      help to cope with mental and physical overstrain, resulting in variety of
      disorders regarding sleep and cardiovascular system; stomach and muscle pains,
      irritability and lack of balance, anxiety. RMT is based on the learning of
      specific perception form-efficient observation on: one's own personality, body,
      functions, thoughts, emotions, and not reasoning. In this way the pathogenic
      attention narrowing is overwhelmed and the behavior changes which reflect on the
      general well-being and self-tolerance. The music in RMT has a starting function.
      RMT is used not only in the case of neurosis therapy, it is successfully applied
      in the preventive medicine as a training method to cope with over-tension and as
      means to prevent emotional alienation in every day life.

PMID- 9190600
TI  - [The general and specific mechanisms of adaptation of the body to extreme
      exposures].
AB  - The authors studied the dynamic of changes in auditory-vestibular system as well
      as the mechanisms of general and specific adaptation of organism to different
      extreme effects. 94 volunteers were examined in conditions of hyperbarism,
      hypobarism, hypergravitation and sea extreme factors. For registration of
      morphological changes and their correlation with biochemical and
      electrophysiological changes, experiments were performed on 272 animals using the
      same extreme factors. Complex clinical, biochemical, electrophysiological
      psychophysiological, and in the animals-morphological studies were performed. The
      state of the auditory-vestibular, cardiovascular, nerve, respiratory systems as
      well as the metabolism of carbohydrates, proteins, lipids, mineral-electrolytes
      and biogenic amines are followed up. It is well known that the immediate
      adaptation to extreme effects occurs on three levels-biochemical, anatomo
      physiological and nerve-psychic. These levels are comparatively independent but
      also mutually related and determining each other. It was found out that in the
      different types of extreme effects the leading role is played by a different
      level. For example in sea extreme effects the nerve psychic adaptation level is
      dominating while in hyperbaric overstrain the anatomo-physiologic level plays the
      leading role. It is found out that 70% of the incidents during divers' experience
      is due to changes mainly in the middle year and in the labyrinth. Attention is
      paid on the role of genotype characteristics of adaptation as well as on the
      organism's tolerance towards the nitrous narcosis and oxidative intoxication. An
      interesting finding is that the animals and volunteers who decrease the blood
      serotonin values following the extreme effect are with higher stability and the
      immediate adaptation occurs quicker and is more effective. There is no data in
      the literature on this topic. These results could be used for prognosing the
      stability of the organism and for decreasing the health risk for the working
      under extreme effects, for their prevention and treatment as well as in the
      professional selection.

PMID- 9190601
TI  - [Complex biomedical studies of the body under conditions of extreme marine
      factors].
AB  - The results of experiments with 50 volunteers are presented, exposed to
      conditions, similar to those of ship-wreck-on rafts and boats anchored in the sea
      and with restricted taking of food and water. Complex medical studies have been
      accomplished. The state of the cardio-vascular, nerve, respiratory and sensor
      systems and the metabolism of certain substances are followed up. The
      electrophysiological studies include: EKG, EEG, ENG, SPO, ZPO, SSEP,
      craniocorpography, computer analysis of the cardiac variability. A part of these
      have been monitored during the whole experiment using Holter records or by cable
      and telemetric way in special laboratories on the beach. The biochemical studies
      include indicators characterizing the metabolism of carbohydrates, lipids,
      proteins, mineral-electrolytes and biogenic amines. Some individual features in
      the course of sea-sickness are described according to the phenotype and the
      genotype characteristics of the adaptation processes. Special attention is paid
      to vestibular-vegetative, neurologic and psychic changes as well as on the
      manifestations of orthostatic collapse, sometimes ending by loss of consciousness
      or epi-fainting. It is considered that the orthostatic collapse is due to the
      combined influence of prolonged vestibular overstrain, hypokinesia, starvation,
      thirst and psycho-emotional stress. This is the possible main cause for the death
      of some saved ship-wreckers. An actualization of the instruction for saving of
      ship-wreckers is recommended with including of a special movement regime in the
      saving devices. Sibellium (flunarizin) is offered as a prophylactic and
      therapeutic agent against sea-sickness.

PMID- 9190602
TI  - [An experimental study of the skin- and eye-irritating action of an artichoke
      preparation].
AB  - Studies for evaluation of the acute and subacute (21 day) dermal toxicity, skin
      irritating, eye-irritating and skin-sensitizing effects of the preparation
      "Artishok" are carried out in order to determine the professional risk in direct
      skin contact during its production. The experiments are performed according to
      the Bulgarian standards and the requirements of OES. It is considered on the
      basis of the studies that the preparation is not able to produce dermal
      intoxications. The maximal single dose of 6000 mg.kg-1 is LD0. After 21 day
      dermal application of the preparation in doses 1000 and 3000 mg.kg-1 there are
      not observed any signs of intoxication, cumulative effect or changes in the
      integral, haematologic and biochemical studies of the white rats. These doses are
      considered to be inefficient. Neither skin-irritating nor eye-irritating effect
      has been proved. The determining of the skin-sensitizing potential of the
      preparation in guinea pigs through a maximizing test reveals lack of skin
      allergic reaction in the conditions of the experiment.

PMID- 9190603
TI  - [The toxicological characteristics of Gastrofenzin. I. Its acute toxicity (oral,
      subcutaneous and intravenous)].
AB  - The acute toxicity of the antiulcer drug "Gastrofenzin", synthesized in Bulgaria
      has been studied in oral, subcutaneous and intravenous application in white rats
      "Wistar" and white mice "ICR". The main toxicometric parameters (LD50, LD16, LD84
      and others) have been determined. The clinical picture of intoxication is
      characterized mainly by symptoms deriving from in the central and vegetative
      nerve system. According to the parameters of acute oral toxicity (LD50 for male
      white rats is 665.0 mg.kg-1 and for female--876 mg.kg-1) and to the
      classification of Hodge & Stemer Gastrofenzin refers to the group of slightly
      toxic drugs. The LD50 in subcutaneous application is 938.0 mg.kg-1 for the male
      and 891.0 mg.kg-1 for the female rats. For the intravenous application LD50 is
      50,1 mg.kg-1 for the male and 43.6 mg.kg-1 for the female rats. The coefficient
      of lethal intoxication danger is below 0.1 in the three ways of application which
      confirms its status according to the upper classification. A significant sex
      difference in the indicators of acute oral toxicity for the white rats and white
      mice has not been observed. The white mice of both sexes seem to be more
      sensitive to the drugs' effects than the white rats.

PMID- 9190604
TI  - [The toxicological characteristics of Gastrofenzin. II. Its subacute oral
      toxicity].
AB  - The subacute (30 day) oral toxicity of Gastrofenzin has been investigated in
      white rats "Wistar" of both sexes, treated with 0.7 and 33 mg.kg-1 for the male
      and 0.9 and 44 mg.kg-1 for the female rats. The applied doses respond
      respectively to the control doses, 1/100 and 1/20 LD50 of the preparation. A
      complex of integral, behaviour, laboratory biochemical and histological methods
      has been used. The findings show that Gastrofenzin in doses 1/100 and 1/20 LD50
      does not exert cumulative effect, reported by the lack of lethal effect among the
      animals. With the help of actograph "AIDA" an increased spontaneous activity is
      reported in the rats from both sexes treated with dose 1/20 LD50 of the
      preparation. Under the experimental conditions the doses of 7 and 9 mg.kg-1
      (1/100 LD50) and 33 and 44 mg.kg-1 (1/20 LD50) do not exert toxic effect on the
      liver, kidneys and brain. Deviations are observed which show increasing of the
      oxidative-metabolic processes and trigger adaptation mechanisms in the above
      mentioned organs.

PMID- 9190606
TI  - The evaluation of forensic DNA evidence. Excerpt from the Executive Summary of
      the National Research Council Report.
AB  - The following is an excerpt from the Executive Summary of the National Research
      Council Report.

PMID- 9190605
TI  - [The toxicological characteristics of Gastrofenzin. III. Its chronic oral
      toxicity].
AB  - A risk evaluation has been carried out under conditions of chronic three-month
      experiment in oral application of Gastrofenzin in doses 1/20, 1/100 and 1/200
      LD50 for male and female white rats, respectively 33.2 and 43.8; 6.7 and 8.8; 3.4
      and 4.4 mg.kg-1. There have been applied integral, behavioural, laboratory,
      biochemical (serum, liver, kidney, brain, brain mitochondria), histologic and
      electron microscopic methods. The highest doses cause functional and biochemical
      changes in the nerve system, liver and the kidneys without involving the
      structural elements of the respective tissues. Significant changes have not been
      observed in the doses 1/100 LD50 and 1/200 LD50. A dose-effect increase has been
      found out in the level of cytochrome-P-450 in the liver tissue, but the data are
      insufficient for determining the type of the caused induction. The results of the
      complex study show that in the three-month application in doses 1/20, 1/100 and
      1/200 LD50 Gastrofenzin does not cause development of significant deviation in
      the organism of the mice from both sexes and its toxicological characteristic is
      comparatively favourable.

PMID- 9190607
TI  - [Photostability of antifungal agents. 2. Photostability of polyene antibiotics].
AB  - The polyene antibiotics amphotericin B, natamycin and nystatin are rapidly
      degraded under the influence of light. Amphotericin B as a heptaene has a
      markedly higher photostability than the tetraenes natamycin and nystatin. With a
      new HPLC method for the separation of the different polyene components we could
      perform a quantitative analysis of the photodegradation process. Initially
      degradation products with unchanged spectrophotometric absorption spectra are
      formed from each of the three polyene antibiotics. Longer light exposure leads to
      the subsequent degradation of the polyene structures. This photochemical
      instability was also detected in various drug products with polyene antibiotics
      as active ingredient. On direct sun exposure of topically applied polyene
      antibiotics a pronounced photodeactivation of the drug substances is expected.

PMID- 9190608
TI  - ["Gentle psychiatry--metamorphosis of violence?"].

PMID- 9190609
TI  - [Mother-child treatment in psychiatry. I: Overview of experiences up to now].
AB  - Basing on the growing interest in the work with relatives of mentally ill people,
      psychiatric inpatient treatment of mentally ill mothers together with their
      infants or toddlers is described. The introductory overview gives an account of
      various international experiences with psychiatric inpatient treatment of mother
      and child, the conditions existing especially in England are described, and hints
      are given in respect of the need to adopt that treatment model.

PMID- 9190610
TI  - [Quality of life for schizophrenic patients--that is.... Results of a survey of
      psychiatrists].
AB  - 605 German psychiatrists were asked what they consider important ingredients of
      the quality of life of schizophrenic patients. Most frequently, quality of life
      was associated with social integration. Work, social contacts and acceptance on
      the part of their environment were considered particularly important in this
      respect. The second rank was occupied by the absence of symptoms of the disorder
      and a sufficient capacity and fitness for work, as well as social competence to
      meet the demands of their social environment, and to be capable of living
      independently. In addition, the limitation to a minimum of suffering from the
      side-effects of psychopharmacotherapy was held to be relevant for the patients'
      quality of life. Adequate psychiatric care was least frequently regarded as a
      prerequisite.

PMID- 9190611
TI  - [The first panic attack: a missed chance for prevention of panic disorder and its
      complications].
AB  - OBJECTIVE: Assessment and analysis of first medical consultations and their
      significance in panic disorder patients. METHODS: 90 panic disorder patients were
      interviewed concerning their experiences with the medical system at the time of
      their first panic attack. RESULTS: Panic disorder patients contacted mostly non
      psychiatric medical services at the time of their first panic attack. The correct
      diagnosis was established in only 4 cases (5.6%). CONCLUSIONS: An important
      chance for secondary prevention of the development of panic disorder is missed,
      probably due to the poor education of physicians on panic attacks.

PMID- 9190612
TI  - [Psychotic symptoms as the initial manifestation of multiple sclerosis?].
AB  - Five case reports with psychiatric disorders prior to the diagnosis of multiple
      sclerosis are presented and discussed in relation to relevant scientific
      literature. Particularly the possibility of a causal correlation between
      psychopathological abnormalities and the CNS-inflammation is investigated.
      According to several reports and the own observations one has to consider the
      possibility of a (pure) psychotic onset of multiple sclerosis. The differential
      diagnosis in patients with psychotic illness should therefore include the
      encephalitic form of MS. Further studies with a standardized setting and a
      definite population basis are necessary to expand the knowledge in the
      epidemiology of psychiatric disturbances in MS.

PMID- 9190613
TI  - [Color vision defects in endogenous depression].
AB  - 8% of the men and approximately 0.5% of the women in a normal population suffer
      from congenital colour anomaly. We examined 75 women suffering from endogenous
      depressions. We found disturbed colour vision in 63% of them. We discuss the
      aetiopathogenic relationship between endogenous depression and disturbed colour
      vision.

PMID- 9190614
TI  - [Subjective criteria of schizophrenic patients in selecting a physician in
      ambulatory care].
AB  - PURPOSE: Several studies Conducted during the last 30 years have shown the high
      prevalence of mental disorder among patients of general practitioners (GPs). The
      integration of out patients care of schizophrenics into primary care remains
      controversial. Yet there is a lack of studies determining the subjective view of
      clients on their choice of their physician. METHODS: In this study we interviewed
      in patient schizophrenics on their choice of physician for out patient care.
      RESULTS: 27.3% were being treated only by a GP, 29.9% only by a psychiatrist and
      36.4% by a GP and a psychiatrist. Those treated only by a GP knew him a lot
      longer. The appraisal was more positive for those treated only by a GP, while
      those treated by both psychiatrist and GP rated the competence of the
      psychiatrist more positive by. CONCLUSIONS: Those treated by both GP and
      psychiatrist had the longest length of illness, yet the lowest rate of
      rehospitalisation. Although these results cannot only be seen as a result of the
      choice of physician, they still confirm the importance of interdisciplinary
      cooperation and should encourage GPs and psychiatrists to recommend their
      schizophrenics to be treated cooperatively.

PMID- 9190615
TI  - [Group stability and open setting in psychiatric therapy groups].
AB  - Psychotherapeutical groups in Psychiatry--different to traditional Psychotherapy-
      are often carried out as open groups; the patient, not bound to a previous
      commitment to long-term and reliable attendance, is authorized to determine for
      himself how long he will take part in the group. Though in this way it is
      possible to decrease the threshold of participation in the group, on the other
      hand this may cause risk of an extreme high fluctuation. The analysis of a group
      of psychiatric patients shows that in spite of the open form, lack of a waiting
      list, and a faint motivation of newly admitted participants, considerable
      stability can be obtained.

PMID- 9190616
TI  - [Patients of a crisis intervention unit 3 and 9 years after their admission].
AB  - 369 patients of a crisis intervention center, treated in 1985, were seen in
      follow-up-studies 3 and 9 years after admission. The catamnesis was done by an
      open questionnaire and standardized inventories. The mean value of hospital stay
      was 3.98 days. Complete data were received from 144 resp. 138 persons. 9 persons
      died by suicide during the first three years after admission. During the next 6
      years most of the patients were stabilized. Minimal effectivity and stability was
      observed for alcoholics and drug dependent patients.

PMID- 9190617
TI  - [Degree of disability of demented patients as judged by relatives and experts
      (disability insurance)].
AB  - Health insurance companies commission medical expert opinions rating the severity
      of clinical improvement in order to provide adequate nursing support. We compared
      these ratings on 28 demented patients with the ratings from carers and with our
      own examination. The results indicate that the expert opinions underestimated the
      severity of improvement and adequate support in some of the cases. We discuss
      whether these discrepancies may be due to the peculiarities of dementia.

PMID- 9190618
TI  - [Risperidone after clozapine in therapy refractory schizoaffective psychosis--a
      case report].
AB  - Recently, American authors pronounced the hypothesis that Clozapine-response may
      be considered as a predictor of response to atypical neuroleptic. We report the
      history of a schizoaffektive patient unresponsive to butyrophenone and
      phenothiazine neuroleptic who was first treated with Clozapine and then with
      Risperidone and who reacted very differently to these atypical neuroleptic.

PMID- 9190619
TI  - [Psychosis in the early stage of HIV infection].

PMID- 9190620
TI  - [What is psychiatry? Psychiatry in German language textbooks--I].

PMID- 9190621
TI  - [Considerations on aging in Cuba].
AB  - This article presents some considerations about how the elderly Cuban population
      is behaving and the challenges for the near future. It also offers information on
      the main characteristics of the old woman in Cuba.

PMID- 9190622
TI  - [Coronary disease in women].
AB  - Coronary heart disease is the leading cause of death among women, with a high
      prevalence in the older women. Women have a less favorable outcome after
      myocardial infarction and after myocardial revascularization procedures. We have
      revised the most up to date published information about risk factors for coronary
      heart disease in women. The most salient features concerning lipids,
      hypertension, diabetes, cigarette smoking, physical activity and obesity are
      summarized. The differences on clinical manifestations of coronary heart disease
      among men and women are also presented. The salient data about estrogen
      replacement therapy effect on coronary heart disease on postmenopausal women is
      also summarized.

PMID- 9190623
TI  - [Dental treatment under general anesthesia offered at the Hospital Pediatrico
      Universitario de Puerto Rico during the years 1989-1994].
AB  - One hundred and fourteen mentally retarded (MR) and non-mentally retarded (NMR)
      patients were divided into two groups and categorized according to the condition
      presented. Age, sex, and type of procedure performed were recorded for each
      patient. On the MR group 32% were over 17 years of age. On the NMR group 51% were
      under 6 years of age. The sex distribution was similar in both groups. Exodontia
      was the most frequently performed dental procedure. The MR group was composed of
      those who presented only mental retardation (42%), cerebral palsy (17%), epilepsy
      (15%), syndromes (7%), endocrinopathies (7%), hydrocephalus (5%) and other
      conditions (7%). The NMR group was composed of those who presented cardiopathy
      (7%), bottle syndrome (42%), hemotopathy (11%), maxillofacial disorders (24%) and
      other conditions (16%).

PMID- 9190624
TI  - [Graduation discourse].

PMID- 9190625
TI  - [Ethical implications of genetic manipulation of life].

PMID- 9190626
TI  - [Results of treatment with continuous ambulatory peritoneal dialysis. One year
      observation].
AB  - Results of one-year dialysis adequacy monitoring in 20 patients treated with
      continuous ambulatory peritoneal dialysis with Baxter dialysis systems were
      presented. Relatively low mortality rate (10%), stable, within accepted range,
      peritonitis rate (1 episode per 16.4 patient-months), and high percentage of
      patients dialysed adequately (75%), let us to conclude, that CAPD may be a safe
      renal replacement therapy modality, which may be, in selected cases, an
      alternative method to hemodialysis.

PMID- 9190627
TI  - [The influence of some surgical procedures on the activity of protein C].
AB  - Protein C is the important regulating factor of coagulation and fibrinolytic
      system. It is known that surgery causes disturbances of haemostasis. The aim of
      work was to study the influence of different kind of surgery on the protein C
      activity. The study contained 102 operated patients in whom vascular operation
      (20), operation of prostate because of carcinoma (20) and hypertrophy (40),
      cholecystectomy (12) and operation of hernia (10) were performed. Protein C
      activity was measured using Kabi Diagnostika test applying chromogenic substrate.
      In the most of patients surgery caused on the 0 and 1st postoperative day the
      decrease of protein C activity and the return to the preoperative values in the
      next few days. The exception was the hernia operation which did not diminish
      protein C activity. It seems that the decrease of protein C after surgery was the
      effect of consumption of it in the extremely activated coagulation and
      fibrinolytic system during operation.

PMID- 9190628
TI  - [Pulmonary complications after partial laryngectomies for cancer].
AB  - The material of patients after partial laryngectomies due to the laryngeal cancer
      in light of pulmonary complications was analyzed. Patients were divided into two
      groups depending on kind of performed operation. The first group consisted of
      patients after vertical laryngectomies, the second after horizontal operations.
      The important protective function of the larynx in comparison with lower airway
      was emphasized. It was pointed out, that after horizontal laryngectomies this
      protective mechanism becomes not sufficient. Cases of aspiration pneumonia as a
      result of horizontal operations were introduced. The important contraindications
      to the horizontal laryngectomies were presented.

PMID- 9190629
TI  - [Secondary osteoporosis in patients with steroid-dependent asthma].
AB  - The aim of the trial was estimation of frequency and degree of osteoporosis in
      steroid-dependent asthma patients (48 persons: 18 men and 30 women). Control
      group created 36 healthy persons. Following measurements were done: quantitative
      computed tomography, radiological estimation of thoracic and lumbal spinal column
      and hands, in serum total alkaline phosphatase, calcium, phosphate, in urine
      excretion of calcium, phosphate and creatinine. Quantitative computer tomography
      revealed secondary osteoporosis in 40.5% asthma patients. These results were
      correlated with estimation of roentgenograms of thoracic and lumbal spinal column
      and metacarpal measurements and less well with total alkaline phosphatase. Time
      of duration of steroid therapy and time of asthma had influence on degree of
      osteoporosis. Moderate development of osteoporosis is probably the result of low
      dose of steroids.

PMID- 9190630
TI  - [Relationship between heart rate and general mortality and that caused by
      cardiovascular diseases].
AB  - The sample of 1309 men and 1337 women, aged 35-64, randomly selected for the
      first Warsaw Pol-Monica screening performed in 1984, was followed up in 1992. All
      deaths were registered according to the cause of death based on death certificate
      diagnosis. The proportional hazard Cox model was used for univariate heart rate
      (HR) analysis and for multivariate analysis after adjustment for covariates (HR
      divided into 4 subgroups). Out of screened subjects 263 persons died (139 due to
      cardiovascular disease CVD). Mean baseline HR of persons who died was 76.8 (+/-
      11.5) versus 73.9 (+/- 10.2) for subjects who survived (p = 0.0001). In the
      univariate analysis the heart rate was significantly positively related both to
      all cause mortality (relative risk RR = 1.29, p = 0.0001) as well as to
      cardiovascular mortality (RR = 1.31, p = 0.0025). In the multivariate analysis HR
      was significantly positively related to all cause mortality (standardized RR =
      1.24, p = 0.0012), but almost significantly related to cardiovascular mortality
      (SRR = 1.20, p = 0.052).

PMID- 9190631
TI  - [The levels of adenine nucleotides and hypoxanthine in blood of patients on long
      term hemodialysis using dialysis fluid containing acetate or bicarbonate].
AB  - Intraerythrocyte adenine nucleotides concentration reflects energy balance of red
      cells and plays pivotal role in their function. In hemodialysed patients both ATP
      and ADP concentration in red cells was higher than in controls, p < 0.001 and p <
      0.005 respectively. But AMP and hypoxanthine did not differ from control. No
      change of ATP, ADP and AMP was observed after hemodialysis, but hypoxanthine fall
      significantly, p < 0.001. The pattern of nucleotides concentration and its
      changes during hemodialysis was the same regardless of the mode of the therapy;
      e.g. acetate or bicarbonate.

PMID- 9190632
TI  - [Environmental factors and blood pressure].

PMID- 9190633
TI  - [The role of calcium antagonists on coronary artery spasm and prevention of
      restenosis after angioplasty].
AB  - Classification, mechanism of action, hemodynamic and electrophysiological effects
      of calcium antagonists also structure of L-type calcium channel (cell receptor
      for this group of drugs) have been presented. Current views about the role of
      calcium channel antagonists in treatment of vasospastic angina pectoris, in
      particular Prinzmetal's angina, have been discussed. The use of calcium
      antagonists for the prevention of coronary restenosis after successful
      percutaneous transluminal coronary angioplasty have been analysed. Beneficial
      effects of calcium channel blockers (diltiazem 180 mg per day and verapamil 480
      mg per day) for the prevention of restenosis after coronary angioplasty in a
      group of patients with stable angina pectoris have been demonstrated. Future
      directions in the trials on the calcium antagonists were been also presented.

PMID- 9190634
TI  - [Arrhythmogenic dysplasia of the right heart ventricle].
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a heart muscle disease in
      which muscle tissue has been partially replaced by adipose or fibro-adipose
      tissue. Morphologic changes in the right ventricle and ventricular arrhythmias
      are characteristic. Pathomorphological changes should be confirmed by NMR or
      endomyocardial biopsy. Morphological changes ought to be found by ultrasound
      methods or angiographic examination. ECG exercise test, Holter monitoring, late
      potentials, total ventricular activation time and programmed stimulation of right
      ventricle are used to evaluate the risk of sudden death due to ventricular
      arrhythmias which is the most important problem. Those methods indicate
      pharmacologic or invasive therapy (RF ablation, implanted cardioverter
      defibrillators), and are used to establish the effectiveness of treatment.

PMID- 9190635
TI  - [Radioisotopic methods of estimating perfusion and viability (metabolism) of the
      myocardium].
AB  - Radioisotope methods play a special role in cardiological diagnostics. At
      present, studies of myocardial perfusion also allow the estimation of
      cardiomyocyte metabolism. These methods are suitable for the detection of
      stunned, hibernating or scarred myocardium as well. The radiopharmaceuticals
      which accumulate in myocardium proportionally to regional blood flow (thallium
      201, MIBI-Tc99m, teboroxime-Tc99m, tetrophosmin-Tc99m, furifosmin-tc99m) are used
      for the estimation of perfusion. In the nuclear medicine departments myocardial
      perfusion imaging can be performed with planar or tomographic (SPECT) methods.
      The techniques have high sensitivity (80%, 90%) and specificity (90%, 80%) for
      detection of coronary artery diseases. The radioisotopic methods have higher
      sensitivity than other noninvasive techniques (ECG sensitivity-60%, specificity
      85%, ECHO sensitivity-81%, specificity-89%). Positron emission tomography is
      still the "gold" standard for the estimation of myocardial viability. This method
      uses substrates for different metabolic pathways (acetate-C-11, amino-acids-C-11,
      fatty acids-C-11, fluorodeoxyglocuse-F-18) labelled with positron emitters.
      Modifications in thallium protocols make estimation of myocardial metabolism
      possible. Recently MIBI-Tc99m has also been used in the assessment of myocardial
      viability. Results of these studies are of great clinical importance. They allow
      to predict a success of a surgical revascularysation and the return of normal
      myocardial function.

PMID- 9190636
TI  - [Peritoneum as a dialysis membrane. II. Pathology].
AB  - Peritoneal dialysis is an established method of treatment of chronic renal
      failure. In that paper morphological and functional changes of peritoneum due to
      the process of long-term dialysis are presented. Morphological changes are
      observed in mesothelial cells, intercellular junctions, interstitial tissue and
      blood vessels. Moreover morphological changes in typical complications of chronic
      peritoneal dialysis, e. g. peritonitis, eosinophilic peritonitis, and sclerosing
      encapsulating peritonitis are described. Mechanisms of functional disorders
      during chronic peritoneal dialysis, involving the decreased permeability of the
      peritoneum, the increased permeability of the peritoneum and the enhanced
      lymphatic drainage are discussed. The article is the second of two parts
      presenting physiology and pathology of peritoneum as dialysis membrane.

PMID- 9190637
TI  - [The influence of multiple dialyzer reuse on selected coagulation parameters].
AB  - The aim of the study was to follow effects of multiple dialyzer reuse on some
      coagulation parameters. In a random group of 10 patients undergoing intermittent
      hemodialysis treatment, platelet coagulant, fibrinogen, BTG and PF4
      concentrations were determined after 1st dialyzer usage and after 2 consecutive
      dialysis sessions after which the dialyzer was reused by manual method with 1%
      Dialyne solution. An increase in fibrinogen concentration after 240 min of HD
      procedure was shown when dialyzer was used for 1st and 3rd time. BTG activity
      increased after 240 min of HI procedure when the dialyzer was used for 3rd time.
      There was a fall in platelet count after 30 min of HD during the 1st and the 3rd
      dialyzer use. The fall in platelet count lasted all dialysis session when
      dialyser was used for 3rd time. The PF4 activity was decreased after 30 min of HD
      session after the 1st and the 2nd dialyzer use.

PMID- 9190638
TI  - [The influence of exertion on the incidence and course of diabetes mellitus].
AB  - Regular physical activity brings some benefits for patients with diabetes: it
      decreases insulin resistance, improves glycaemic tolerance and the state of the
      cardiovascular system, regulates blood lipid profiles and increases the
      fibrinolytic activity of plasma. All these factors improves the quality of life
      and professional rehabilitation of diabetic patients. Taking into consideration
      all contraindications kinesis therapy, together with diet and pharmacological
      treatment should be recommended as an important factor in the management of
      diabetes mellitus, especially NIDDM.

PMID- 9190639
TI  - [The role of intracellular activation of enzymes in pathogenesis of acute
      pancreatitis--literature review].
AB  - Pathophysiology of acute pancreatitis (AP) is not full clear to present-day.
      Current review shows an importance of experimental models of AP with observations
      of intracellular changes during early stages of disease. One of the actual
      opinion suggest that abnormality in intracellular transport, secretion with
      intracellular activation of enzyme protein plays an important role in evolution
      of AP. These events further start cascade reactions and lead to autodigestion of
      pancreas.

PMID- 9190640
TI  - [Foreign body imitating bronchial neoplasm].
AB  - A case of 53 year-old male admitted to the Clinic with fever and persisting cough
      with a muco-purulent secretion, varying in intensity for about 4 months, was
      presented. Prior to the admission to the Clinic the patient was treated with
      antibiotics, which only slightly relieved the symptoms mentioned above. The
      patient was admitted to the Clinic with diagnosis of chronic bronchitis, right
      sided bronchopneumonia with a suspicion of lung cancer. Performed chest X-ray
      seemed to confirm this diagnosis. Later on, tomography scans and bronchoscopy
      demonstrated a foreign body in the bronchus. Bronchoscopy not only allowed to
      exclude neoplastic change but also enabled us to "treat" the patient by
      extracting his molar tooth remained in the main right bronchus, which caused
      purulent inflammatory changes in this bronchus. After subsequent antibiotic
      therapy patient's general condition improved and radiological chest image
      returned to normal. Persistent cough and recurrent fever are often the symptoms
      of the lung cancer. It should be emphasised that in the observed case longterm
      treatment of these changes lasted for 4 months without chest radiological
      examination.

PMID- 9190641
TI  - [Acute renal insufficiency during Candida albicans candidiasis in a 2-month old
      infant].
AB  - In this paper has been described the case of 2-month old infant with acute renal
      insufficiency caused by mechanical obstacle of fungal bezoars. Bilateral
      pyelostomy has been performed and fungal masses have been washed out from kidney
      pelvis. The applied treatment including administration of Fluconazole
      intravenously caused disappearance of acute renal insufficiency. In this paper
      authors described pathogenesis, clinical symptoms, and treatment of urinary tract
      fungal infection.

PMID- 9190642
TI  - [What is your diagnosis? Scimitar syndrome (= hypogenetic lung syndrome)].

PMID- 9190643
TI  - [Can myocardial damage following heart infarct be reversible?].

PMID- 9190644
TI  - [Cardiac interventions in Switzerland].
AB  - For the year 1995, as for the previous 10 years, a survey of cardiac invasive and
      surgical procedures in Switzerland was carried out by a standardised
      questionnaire. At the 25 Swiss centres (10 public non academic, 10 private and 5
      academic centres) a total of 11,198 coronary revascularisation procedures were
      performed, the majority of them (60%) by percutaneous transluminal coronary
      angioplasty (PTCA). Of all PTCAs, 89% were single vessel interventions. PTCA for
      ongoing infarction accounted for 6% of all PTCAs. The use of coronary stents has
      increased to 28% of all angioplasties. Other devices like directional atherectomy
      and rotablations have lost ground (41 cases). Thirteen interventions with
      intracoronary laser catheters were recorded. Among the new diagnostic tools, only
      coronary ultrasound has been used regularly (191 cases). Percutaneous balloon
      valvuloplasties (64 cases) and catheter closure of congenital shunt defects (32
      cases) remained rare interventions. Procedure related mortality for PTCA was
      0.7%, infarction occurred in 1.1% and emergency coronary artery bypass grafting
      (CABG) became necessary in 0.7%. For the first time, the total number of CABGs
      (4485) decreased. Among the 2077 non-coronary operations, 56% were performed for
      valve disease and 44% for congenital heart disease. Heart transplantation was
      performed in 44 patients. The majority of interventional catheter procedures were
      performed at the 5 university centres whereas the majority of CABGs were carried
      out at private centres. Four centres performed diagnostic procedures,
      exclusively. In-house surgical stand-by for PTCA was present in 17 of the 21
      interventional centres.

PMID- 9190645
TI  - [Magnetic resonance tomography in osteoid osteoma: more confusion than benefit?].
AB  - The purpose of this evaluation was the description of potentially misleading MR
      appearances of osteoid osteoma. The MR images of 10 patients with osteoid osteoma
      were retrospectively evaluated and compared to radiographic, intraoperative and
      histologic findings. 4 of the 10 abnormalities were located in the proximal
      femur, two in the lumbar spine, and one each in the tibial plateau, in the
      cervical spine, in the sacrum and in the first metacarpal. 8 of the 9 nidi
      visible on standard radiographs and/or CT scans were demonstrated on MR images.
      Edema was visible within the bone marrow in 3, within soft tissue in 2 and in
      both locations in 4 MR examinations. The soft tissue abnormalities were
      circumscribed in 3 patients and could be misdiagnosed as soft tissue tumors or an
      abscess in these patients. One of 5 osteoid osteomas located in the proximity of
      a joint mimicked septic arthritis. The MR appearance of osteoid osteoma may be
      misleading. However, false diagnoses usually can be avoided with a careful search
      of a nidus. MR imaging in osteoid osteoma is important for differential
      diagnosis.

PMID- 9190646
TI  - [Indications in sleep-apnea syndrome. When and why is further assessment
      meaningful?].
AB  - Forms of sleep apnea syndrome: Interrupted breathing and hypoventilation during
      sleep lead to sleep disorders and to cardiovascular sequelae. In the common
      obstructive sleep apnea syndrome (OSAS) apneas are related to intermittent
      obstruction of the upper airways. In the rarer central sleep apnea syndrome
      certain cardiovascular or central nervous system disorders lead to disturbed
      regulation of respiration connected with periodic breathing. Signs indicating
      OSAS: Loud, cyclic snoring, interrupted by cessation of breathing during sleep
      observed by relatives and excessive daytime to diurnal sleepiness indicate OSAS.
      Furthermore alteration of personality, headache in the morning, non-refreshing
      sleep and nocturnal choking sensations may indicate OSAS. When is evaluation
      necessary? Patients with complaints possibly induced by OSAS should be further
      evaluated since nocturnal application of continuous positive airway pressure
      (CPAP) by means of a nose mask and other treatment forms often lead to
      significant improvement of OSAS. In addition patients with untreated OSAS have an
      increased risk for car accidents and premature death as consequence of
      cardiovascular diseases. The type and extent of a supposed respiratory disorder
      is evaluated by means of a sleep study.

PMID- 9190647
TI  - [Cholestasis and increase in transaminases in pregnancy].

PMID- 9190648
TI  - [Experimental enteral segmental transplant. Functional response and surgical
      complications].
AB  - BACKGROUND DATA: Total enteral transplant associated or not to other abdominal
      organs has a high degree of morbidity due to immunologic and functional
      complications that have limited its therapeutic application. Segmentary
      transplants have demonstrated experimentally to have a better control to immune
      response, however there are still doubts on its functional effectiveness in terms
      of other segments. OBJECTIVE: In order to evaluate surgical and functional
      morbidity without immunologic interference, syngenic segmentary enteral
      transplants were done, from three different levels in the intestine. METHOD:
      Growing syngenic Lewis rats were randomly divided into five groups; four of them
      had 90% enterectomy with a simultaneous transplant of a 30% of the proximal,
      medial and distal segments in the first three groups and 90% in the fourth one.
      The fifth group was used as a control. RESULTS: Of the 54 rats that were
      transplanted, one third developed late complications. Only half of them showed
      controllable causes, the complications were proportional in all groups. Among
      surviving four months after transplant, no group had stopped growing, however,
      the proximal transplant group had significant (P < 0.05) deficit in weight with
      respect to the other groups. All the other groups showed growth patterns similar
      to the control group. Plasma concentrations of tryglicerydes, cholesterol and
      glucose after the maltosa test were similar in all animals. Low albumin
      concentrations were observed only in the proximal transplant group (P < 0.05).
      CONCLUSIONS: Medial and listal segmentary transplants showed the best functional
      adaptability in terms of ponderal growth, similar to animals with total enteral
      restitution or intestinal integrity.

PMID- 9190649
TI  - [Helicobacter pylori infection and gastric cancer in Mexico. A challenge for
      prevention and population control].
AB  - The International Agency for Research on Cancer (IARC) of the WHO has recognized
      a cause-effect relationship between Helicobacter pylori (Hp) infection and
      gastric cancer of such magnitude that the presence of this infection increases
      the risk of gastric cancer approximately four times. Gastric cancer is currently
      the second cause of mortality due to malignant neoplasms in Mexico City. This
      article explores the association between Hp infection and gastric cancer
      incidence through an epidemiological study including 109 gastric cancer patients
      and 177 hospital controls in Mexico City. The study estimates that, in the
      population studied, Hp infection was present in 87.2% of the cases, compared with
      82.5% of the controls. The odds ratio of having gastric cancer if infected with
      Hp was 1.44 IC95% 0.7-2.8. In addition, it was calculated that with eradication
      of Hp infection in the general population, gastric cancer incidence would
      decrease by at least 26.6%. An improvement of the actual sanitary conditions
      along with the development of an effective vaccine for Hp infection and the
      existence of increasingly effective treatments to eradicate the bacteria are the
      necessary next step for populational prevention and control of gastric cancer.

PMID- 9190650
TI  - [Endoscopic management of biliary fistula].
AB  - OBJECTIVE: To assess safety and efficacy of endoscopic therapy for patients with
      a postoperative biliary fistula. BACKGROUND: Biliary fistula that occur after
      operations on the biliary tract may be due to bile duct injury or distal bile
      duct obstruction. These fistulas has been managed with surgical correction. At
      present, endoscopic methods of improving biliary drainage has been found to be
      highly successful in the management of postsurgical biliary leaks. PATIENTS
      METHODS-RESULTS: By endoscopic cholangiopancreatography (ERCP) we diagnosed 35
      patients (23 females and 12 males) with postoperative biliary fistula. Four
      patients had history of laparoscopic cholecystectomy. We used endoscopic
      sphincterotomy (18 cases) or endoprosthesis placement (17 cases) in the
      treatment. Seventeen patients with fistula plus common bile duct (CBD) stones and
      one patient with benign papillary stenosis were treated with endoscopic
      sphincterotomy alone. Seventeen patients without CBD stones were treated with
      only endoprosthesis placement. A second ERCP confirmed healing of the leakage
      after 4-16 weeks. CONCLUSIONS: Postoperative bile leakage could be diagnosed
      safely and effectively by ERCP, subsequent endoscopic management in most cases is
      successful. Sphincterotomy alone is the preferred treatment for biliary fistula
      complicating surgery for gallstone disease. Alternatively, when a fistula is
      large, endoscopic placement of an endoprosthesis can be proposed as the first
      treatment.

PMID- 9190651
TI  - [Hepatocellular carcinoma. Experience at the Instituto Nacional de Cancerologia].
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a rare tumor in Mexico. Stands in
      the 21st place, corresponding to 1.4% of all malignant tumors. However in
      Southeast Asia, Japan and Sub-Sahara Africa, its incidence is very high.
      Frequently this tumor is diagnosed in late clinical stages and curative surgery
      is difficult to perform. OBJECTIVES: To analyze the general features of patients
      with HCC, and its management in our hospital. METHODS: An observational,
      transversal retrospective study was performed with 63 patients with histological
      proved HCC. RESULTS: Thirty-two were male (50.7%) and 31 female, the mean age was
      56 years, 18 had history of alcohol abuse. Liver enlargement, abdominal pain and
      weight loss were the most common clinical manifestations. The alpha-fetoprotein
      (AFP) was positive in 55% of the patients, ultrasonography and computed
      tomography were the most useful studies. Fifty-six percent had associated chronic
      liver pathology, of which 51% had alcoholic cirrhosis, 43% had cirrhosis of other
      undetermined origin, and 6% had chronic hepatitis. Seventy percent were diagnosed
      in clinical stage II, 17% in stage III. Only 31% were taken to surgery, of which
      laparotomy and liver biopsy was performed in 70%, liver resection in 15%, liver
      dearterialization in 15%. Fifty-four percent of all cases did not received any
      kind of treatment. Postoperative complications occurred in 25% and the operative
      mortality was 20%, with a mean survival time of 10 months. CONCLUSIONS: HCC is a
      rare tumor in our country. All cases were diagnosed in late clinical stages. The
      male-female ratio was 1:1. AFP was positive in only 55% of cases. Due to the late
      stages at presentation or poor clinical conditions, most tumors were considered
      irresectable, thereby other forms of management need to be evaluated in order to
      define its place. It is important to identify patients with higher risk of HCC
      for an early detection and management.

PMID- 9190652
TI  - [Mexican consensus on Helicobacter pylori. National Consensus Group of the
      Mexican Association of Gastroenterology].

PMID- 9190653
TI  - [Colitis cystica profunda. A case report].
AB  - OBJECTIVE: To present a pathology not previously informed in national literature.
      BACKGROUND: Colitis cystica profunda (CCP) is a rare benign entity and with an
      unknown etiology. There are 148 cases documented in world literature at the
      present time. Histologically it is defined as the obliteration of lamina propria
      by fibroblasts and the presence of submucous cysts. It comes in localized,
      segmental or diffuse forms and associated to other entities as solitary rectal
      ulcer, rectal prolapse, alterations in the pelvic floor, etc. Treatment can be
      medical or surgical according to severity of its manifestations. METHOD: A case
      of CCP is revised as well as the treatment effectuated. RESULTS: A case of
      patient with the diagnosis of CCP of localized type is presented, which principal
      symptom was transanal mucous secretion; on physical exploration a sessile mucous
      polypoid formation at 8 cm from anal verge was found and was treated with
      surgical resection with a satisfactory outcome. CONCLUSIONS: In a patient with
      alterations in pelvic floor or puborectal bundle contraction and sigmoidorectal
      intussusception CCP must be suspected. Treatment can be medical with a high
      percentage of failure being optimal treatment the surgical one.

PMID- 9190654
TI  - [Treatment of liver metastasis of endocrine tumors of the pancreas].
AB  - The aim of this review article is to analyze the diagnostic approach,
      presentation and therapeutic modalities in patients with liver metastasis from
      endocrine tumors. The paper shows the "state of the art" of therapeutic
      approaches with emphasis on the roll of different surgery, radio and
      chemotherapy, arterial embolization and other palliative procedures. The overall
      results of each of this modalities are also shown.

PMID- 9190656
TI  - [Clinical images in gastroenterology. Barrett esophagus of distinctive type and
      adenocarcinoma].

PMID- 9190655
TI  - [Clinical images in gastroenterology. Caroli's disease and congenital liver
      fibrosis].

PMID- 9190657
TI  - [Biographical sketch of Dr. Manuel Arnoldo Barrera Maldonado].

PMID- 9190658
TI  - [Biographical sketch of Dr. Rodrigo F. Barragan Villarreal].

PMID- 9190659
TI  - [Biographical sketch of Dr. Alfonso Perches Vega].

PMID- 9190660
TI  - [Presidential transition address: the Mexican Association of Gastroenterology].

PMID- 9190661
TI  - [Presidential acceptance address: the Mexican Association of Gastroenterology].

PMID- 9190662
TI  - [Treatment of irritable colon with lidamidine and support psychotherapy].
AB  - To evaluate the usefulness of lidamidine treatment in patients with irritable
      colon syndrome, a controlled double blind study was carried out. Forty patients
      with Manning symptom criteria and negative screening to stool examination,
      rectosigmoidoscopy and barium enema were included. Four groups of treatment were
      randomly integrated: Lidamidine with and without group psychotherapy and placebo
      with and without group psychotherapy, for six weeks. After a washout period,
      treatment was switched. Thirty-eight patients with a total of 76 observations
      were evaluated. Favorable response was shown by 94.7% and 68.4% of those who
      received only lidamidine and placebo, respectively, and by 84.3% and 63.2% of
      those who additionally received psychotherapy. Difference with or without
      psychotherapy was not significant. Globally, response was better with lidamidine
      than with placebo (89.5% vs 65.8%, p = 0.02). Adverse reactions were minimum.
      Lidamidine can be a useful drug in the treatment of irritable colon syndrome.

PMID- 9190663
TI  - [HIV infection: future perspective for a so-called fatal disease?].
AB  - During the last 18 months, our knowledge and possibilities in the field of HIV
      infections have progressed in four principal domains: (1) better understanding of
      the dynamics of HIV infections and in particular of the importance of viral
      replication during the phase of latency, (2) possibility of measuring the viral
      charge and its use for diagnosis and to follow treatment, (3) access to very
      effective new anti-retroviral substances which permit hope of long-term
      stabilization of the infection, (4) clinical demonstration that combined
      treatments are superior to monotherapy. While, at the beginning of 1996, only
      three medications were commercialized, there were eight at the end of that year.
      This paper describes the implications for daily practice of recent scientific
      discoveries in the field of HIV infection. The importance of compliance is
      discussed, as well as that of clinical research.

PMID- 9190664
TI  - [Community-acquired pneumonia: considerations on ambulatory management].
AB  - Community-acquired pneumonia is a frequent disease in outpatients; its incidence
      is highest among persons at the extremes of age. Hospitalization is rarely
      required. Since most clinical studies are performed with hospitalized patients,
      available data are not always representative of the general population. For
      instance, the importance of some organisms, such as Mycoplasma pneumoniae, is
      underestimated, and the severity of the prognosis is overestimated in the
      literature. Identification of the causative organism is usually not cost
      effective in outpatients. Therefore, therapy is most often empirical. In
      Switzerland, the majority of patients can be successfully treated with
      macrolides. Antibiotics may also be chosen according to the most probable
      organisms in a given patient, based on his age and underlying diseases; this last
      strategy may be more logical from the point of view of public health.

PMID- 9190665
TI  - [Routine cases in intestinal parasitology].
AB  - The majority of intestinal parasites isolated in Switzerland is imported by
      refugees and travellers. Nematodes are more frequently isolated in the first
      group, whereas Giardia duodenalis and Strongyloides stercoralis predominate in
      the second. Symptoms are usually mild, but occasionally diarrhea, abdominal pain
      and weight loss may be encountered. Hypereosinophilia occurs frequently with some
      parasites. Four cases chosen from the outpatient department of a Swiss medical
      polyclinic are presented and serve as a basis for discussing persistent and
      chronic diarrhea, acute traveller's diarrhea, and hypereosinophilia. Differential
      diagnosis according to type and duration of symptoms, laboratory findings and
      treatment of the most frequently encountered parasites are reviewed.

PMID- 9190666
TI  - [Quality of care: from theory to practice].
AB  - Quality of care is growing concern among health care professionals and managers.
      As a multidimensional concept, it cannot be reduced to simple customer
      satisfaction. Taking into account the views of the three major players in the
      health care system-patients, providers and payers-quality can be defined as the
      capacity to satisfy patients' needs according to professional knowledge and
      within available resources. Efficacy, efficiency, appropriateness, acceptability,
      legitimacy and equity are dimensions of health care quality. Contrary to popular
      belief, quality is neither maximum performance, nor satisfaction at all costs,
      nor punishment or elimination of "bad apples". In ambulatory medicine, quality
      implies first of all the ability to master the processes occurring during an
      office visit. However, although history taking and physical examination are the
      cornerstones of medical practice, they have not been well studied. Improving
      quality of care in the ambulatory sector will require better knowledge about
      medical decision-making processes, in particular identification of the most
      relevant information required for a decision and the optimal way of obtaining it
      in any specific clinical situation.

PMID- 9190667
TI  - [Chronic occlusive arteriopathy of the lower limbs: therapeutic approach].
AB  - Chronic arterial insufficiency of the lower limbs is characterized by
      intermittent claudication often localized to the calf. These early clinical
      symptoms are the results of the atherosclerotic process of the vasculature of the
      lower extremities. The treatment is aimed at reducing or eliminating the ischemic
      pain and at preventing progression of the atherosclerotic disease. Whether
      surgical or nonsurgical measures are used, the cornerstone of patient care lies
      in correction of the risk factors. Smoking cessation and exercise therapy remain
      the fundamental measures in medical treatment of intermittent claudication.
      percutaneous transluminal angioplasty is an appropriate therapeutic option under
      certain criteria, especially for the iliac arteries. In the absence of randomized
      studies, surgery remains the treatment of choice for peripheral revascularization
      in presence of limb-threatening ischemia or ischemic ulcers. New procedures and
      materials are presently under trial to test the safety and efficacy of
      alternative methods or revascularization that would provide better long-term
      patency rates and shorter hospitalization periods.

PMID- 9190669
TI  - [Hydatid cyst of the kidney].

PMID- 9190668
TI  - [Is molecular biology useful to the practitioner?].
AB  - The relative importance of molecular biology in clinical practice is often
      underestimated. However, numerous procedures in clinical diagnosis and new
      therapeutic drugs have resulted from basic molecular research. Furthermore,
      understanding of the physiological and physiopathological mechanisms underlying
      several human diseases has been improved by the results of basic molecular
      research. For example, cloning of the gene encoding leptin has provided
      spectacular insights into the understanding of the mechanisms involved in the
      control of food intake and body weight maintenance in man. In cystic fibrosis,
      the cloning and identification of several mutations in the gene encoding the
      chloride channel transmembrane regulator (CFTR) have resolved several important
      issues in clinical practice: cystic fibrosis constitutes a molecular defect of a
      single gene. There is a strong correlation between the clinical manifestations or
      the severity of the disease (phenotype) with the type of mutations present in the
      CFTR gene (genotype). More recently, identification of mutations in the gene
      encoding a subunit of the renal sodium channel in the Liddle syndrome has
      provided important insight into the physiopathological understanding of
      mechanisms involved in this form of hereditary hypertension. Salt retention and
      secondary high blood pressure are the result of constitutive activation of the
      renal sodium channel by mutations in the gene encoding the renal sodium channel.
      It is speculated that less severe mutations in this channel could result in a
      less severe form of hypertension which may correspond to patients suffering from
      high blood pressure with low plasma renin activity. Several tools, most notably
      PCR, are derived from molecular research and are used in everyday practice, i.e.
      in prenatal diagnosis and in the diagnosis of several infectious diseases
      including tuberculosis and hepatitis. Finally, the production of recombinant
      proteins at lower cost and with fewer side effects is used in everyday clinical
      practice. Gene therapy remains an extraordinary challenge in correcting severe
      hereditary or acquired diseases. The use of genetically modified animal cell
      lines producing growth factors, insulin or erythropoetin, which are subsequently
      encapsulated and transferred to man, represents an attractive approach for gene
      therapy.

PMID- 9190670
TI  - Phylogenetic analysis.

PMID- 9190671
TI  - Evaluating biologics.

PMID- 9190672
TI  - How much pain for cardiac gain?

PMID- 9190673
TI  - A scientific result without the science.

PMID- 9190674
TI  - Can cloning help save beleaguered species?

PMID- 9190676
TI  - Stretching is good for a cell.

PMID- 9190675
TI  - A new face for human ancestors.

PMID- 9190677
TI  - Type Ia supernovae: their origin and possible applications in cosmology.
AB  - Spectroscopic and photometric evidence indicates that Type Ia supernovae (SNe Ia)
      are the thermonuclear explosions of accreting white dwarfs. However, the
      progenitor binary systems and hydrodynamical models for SNe Ia are still
      controversial. The relatively uniform light curves and spectral evolution of SNe
      Ia have led to their use as a standard candle for determining cosmological
      parameters, such as the Hubble constant, the density parameter, and the
      cosmological constant. Recent progress includes the calibration of the absolute
      maximum brightness of SNe Ia with the Hubble Space Telescope, the reduction of
      the dispersion in the Hubble diagram through the use of the relation between the
      light curve shape and the maximum brightness of SNe Ia, and the discovery of many
      SNe Ia with high red shifts.

PMID- 9190678
TI  - Antiretroviral drug trials.

PMID- 9190679
TI  - Antiretroviral drug trials.

PMID- 9190680
TI  - May I see your license, please? Varmus to rule in fight over cell-sorting
      technology.

PMID- 9190681
TI  - May I see your license, please? PCR patent tangle slows quick assay of HIV
      levels.

PMID- 9190682
TI  - May I see your license, please? Exclusive license rankles genome researchers.

PMID- 9190684
TI  - Partners heed Japan's funding plea.

PMID- 9190683
TI  - Privatized cancer journal triggers Senate reaction.

PMID- 9190685
TI  - How the nucleus gets it together.

PMID- 9190686
TI  - Physics, biology meet in self-assembling bacterial fibers.

PMID- 9190687
TI  - No bones about a genetic switch for bone growth.

PMID- 9190688
TI  - Breathing with chlorinated solvents.

PMID- 9190689
TI  - Twins: en route to QTLs for cognition.

PMID- 9190690
TI  - Lessons from litigation over silicone breast implants: a call for activism by
      scientists.

PMID- 9190691
TI  - Dating the Ngandong humans.

PMID- 9190692
TI  - Arachnoid cysts in adults: experience with internal shunts to the subdural
      compartment.
AB  - Twelve patients (10 males, 2 females) with symptomatic arachnoid cysts of the
      middle cranial fossa (9 patients) or overlying the frontal cortex (3 patients)
      were included. Under local anesthesia, an internal shunt was implanted from the
      cyst to the subdural compartment. Postoperative computed tomography scans showed
      volume reduction in eight patients. Permanent clinical improvement was also seen
      in eight patients. In the remaining four, the improvement was only temporary or
      partial, necessitating additional surgery in three patients. Complications (two
      subdural hematomas, one subdural infusion), were observed in three patients, all
      with large cysts. The complications were treated without sequelae. Internal
      shunts may be tried in adults as the first treatment for this condition.

PMID- 9190693
TI  - Management outcome in third ventricular colloid cysts in a defined population: a
      series of 40 patients treated mainly by transcallosal microsurgery.
AB  - BACKGROUND: Third ventricular colloid cysts account for 0.5% - 1.5% of all
      intracranial tumors. A thorough search of the world literature since 1858
      revealed 1167 cases, for which a more than one-third (36%) management mortality
      was estimated. One third of the reported cases had modern diagnostics and surgery
      with minimal morbidity and nearly no mortality. The primary goal of this study
      was to assess the incidence and present-day management outcome of these lesions
      in the strictly defined area of Eastern Finland. METHODS: In a series of 2000
      patients with brain tumors from our catchment area (870,000 inhabitants in
      eastern Finland) during a 14.5-year period (years 1980-1994), 40 patients (mean
      age, 45 years; range, 19-75 years, with 21 females) had a third ventricular
      colloid cyst. Thirty-one patients had transcallosal extirpation of their cysts.
      One additional tumor was extirpated by the infratentorial supracerebellar route
      to include simultaneous biopsy of a tectal tumor (lipoma). One elderly male with
      severe cardiac disease received a ventriculoatrial shunt. Five patients, admitted
      deeply unconscious, died. In two of these five patients, desperate shunting
      operations were done, but, in the remaining three moribund patients, no treatment
      was considered to be of any benefit. Two patients with small tumors are being
      followed up. RESULTS: The far lateral transcallosal transforaminal extirpation of
      the cyst has served our patients well. There was no surgical mortality. The
      outcome was excellent in 30 patients and good in 3 patients. Follow-up time
      ranged from 2 months to 14.5 years (mean, 4.3 years). There were no tumor
      recurrences. Despite good surgical results, management mortality was as high as
      13%, CONCLUSIONS: The incidence of third ventricular colloid cysts is at least
      3.2/1 million/1 year. Even nowadays, up to one fifth of these completely benign
      and treatable tumors are detected too late, with calamitous consequences.

PMID- 9190694
TI  - Dissecting aneurysm of the anterior cerebral artery causing hemorrhagic
      infarction.
AB  - BACKGROUND: Dissecting aneurysms of the cerebral arteries are infrequent, and
      they occur preferentially in the middle cerebral, internal carotid, and
      vertebrobasilar arteries. The anterior cerebral artery (ACA) is usually involved
      in association with dissection in other locations, but a lesion confined to the
      ACA is an extremely rare event. No previous reports have well documented the
      clinical and pathological features of the ACA dissection. Moreover, surgical
      management for this lesion has not been reported. CASE REPORT: A case of
      dissecting aneurysm confined to the ACA causing hemorrhagic infarction is
      presented. To prevent subsequent rupture, we employed a trapping procedure 12
      days after the onset. A dark purplish discoloration of the right A2 portion was
      encountered, with an intact anterior communicating complex. The involved vessel
      was partly sectioned for further pathological examination. RESULTS:
      Pathologically, subintimal clots dissected the vascular lumen in the inner layer
      of the media. Other abnormalities such as deficiency of the internal elastic
      lamina and medial defects were not found. The postoperative clinical course was
      not eventful. CONCLUSIONS: This is the first case to document an ACA dissecting
      aneurysm treated by a direct surgical approach. Spontaneous resolution is not
      infrequent in cerebral dissection, but subsequent rupture has commonly resulted
      in poor outcome. Surgical management is thought to be the most effective method
      to prevent further hemorrhagic event, even for an ACA dissection.
      Revascularization distal to the compromised artery should be considered whenever
      necessary.

PMID- 9190695
TI  - Giant posterior cerebral artery aneurysm in a 4-year-old child: case report.
AB  - Posterior cerebral artery aneurysms in children aged 5 years or less are very
      rare. We were able to find only 10 cases previously described in the literature.
      We present a case of giant bilobulated aneurysm of the distal right posterior
      cerebral artery in a 4-year-old child with an initial history of spontaneous
      subarachnoid hemorrhage. The aneurysm was clipped and the patient had full
      recovery. Based on the literature review, we discuss the characteristics of these
      rare aneurysms, making a comparison with different age groups.

PMID- 9190696
TI  - A large thrombosed superior cerebellar artery aneurysm: a case report.
AB  - MATERIAL AND RESULT: A large thrombosed aneurysm arising from the distal superior
      cerebellar artery was successfully resected. DISCUSSION AND CONCLUSION: An
      aneurysm in this location is very rare. Accumulation of intraoperative
      hemodynamic data may be useful in evaluating the capacity of collateral
      circulation.

PMID- 9190697
TI  - Vein of Galen aneurysmal malformation in an adult: a case report.
AB  - We report a 19-year old woman with a choroidal-type vein of Galen aneurysmal
      malformation who presented with hydrocephalus. This venous malformation was fed
      by multiple fistulas and drained into the superior sagittal sinus through a
      persistent falcine sinus (precursor of the straight sinus). The hydrocephalus was
      treated by ventriculoperitioneal shunting, and the patient remained well for 9
      years. At this time, magnetic resonance imaging (MRI) and magnetic resonance
      angiography demonstrated a vein of Galen aneurysmal malformation in the right
      thalamus, with a Chiari I appearance. This case may provide valuable data
      regarding the natural history of such venous malformations.

PMID- 9190698
TI  - Intracranial extension of paranasal sinus mucocele: two case reports.
AB  - In two cases intracranial extension of mucoceles of the paranasal sinus was
      safely removed by intranasal evacuation and drainage of the lesions located in
      the paranasal sinus. The diagnosis was ascertained in both cases via intranasal
      approach. In addition, the volume of the intracranial lesions was reduced. This
      procedure is both effective and a less invasive diagnostic treatment for the
      lesion.

PMID- 9190699
TI  - Central neurocytoma: clinical, immunohistologic, and biologic findings of a human
      neuroglial progenitor tumor.
AB  - BACKGROUND: Central neurocytomas are rare brain tumors recognized by their
      typical radiologic and histologic features. In general, a good prognosis is
      achieved by total removal. The histogenesis is still under debate, but a neuronal
      origin is widely assumed. METHODS: This study presents the clinical and
      immunohistologic findings of five patients and the results of cell culture
      experiments of two patients with central neurocytoma treated surgically between
      1983 and 1993. RESULTS: The patient age at diagnosis ranged from 21 to 30 years
      (mean, 25 years). The male-to-female ration was 1:4. Raised intracranial pressure
      due to hydrocephalus was the main cause of the clinical manifestations. Total
      resection was achieved in two cases. Four patients received radiotherapy. One
      patient suffered a recurrence 1 year after surgery, requiring a second resection
      and radiotherapy. Follow-up studies took place between 1 and 10.5 years (mean,
      7.1 years). To date, all patients are free of their tumors. Two patients suffered
      from permanent memory disturbances after surgery. Immunohistochemistry confirmed
      the neuronal nature of the tumors. Cell-culture studies, which have been carried
      out for the first time, demonstrated concomitant expression of neuronal
      (synaptophysin) and glial (GFAP) markers. CONCLUSION: Total removal is the
      therapy of choice. In tumor recurrence or limited surgery (e.g. due to severe
      affliction of the fornical structures), radiotherapy has shown to be efficacious.
      The cell-culture experiments give new insight on the histogenesis of central
      neurocytoma, indicating that the tumor arises from an undifferentiated precursor
      cell with the capacity of bipotential neuroglial differentiation.

PMID- 9190700
TI  - Neurocysticercosis and HIV infection: report of two cases and review.
AB  - BACKGROUND: With the progression of acquired immunodeficiency virus (AIDS) and
      human immunodeficiency virus (HIV) infection to endemic areas of cysticercosis,
      the simultaneous diagnosis of both diseases is an expected event. METHODS: Among
      91 patients with AIDS or HIV infection studied from 1987 to 1993 at a neurologic
      reference center in Mexico City, 2 patients with AIDS and neurocysticercosis were
      found. Five previously reported cases were jointly reviewed. RESULTS: The first
      patient presented with increased intracranial pressure of rapid progression. A
      single giant cyst was surgically excised and cysticercus was confirmed on
      histopathologic examination. The second patient had brain toxoplasmosis and
      concurrent neurocysticercosis as an incidental finding. CONCLUSIONS:
      Neurocysticercosis in HIV infection/AIDS may appear as a life-threatening
      condition or as an incidental finding. All reported cases have been found in
      advanced stages of HIV infection. Management must be individualized depending on
      the clinical form of cysticercosis, stage of HIV infection, and coexisting
      opportunistic conditions. Surgery may be lifesaving and some patients apparently
      responded to cysticidal drugs.

PMID- 9190701
TI  - Neurochemical effects of static magnetic field exposure.
AB  - BACKGROUND: There has been considerable interest in both the lay and scientific
      media concerning the putative effects of exposure to electromagnetic fields. An
      assessment of the effects of static magnet exposure on neurochemistry was
      undertaken to determine potential risks to patients and staff involved with
      magnetic resonance imaging and spectroscopy. METHODS: One set of rats were
      exposed to weak static field (800 gauss [G]) in an otherwise normal laboratory
      surrounding. Another set of rats were exposed to 7-Tesla fields, both with
      suitable controls. RESULTS: Exposure of rats (n=8) to weak static fields for
      periods between 12 hours and 8 days produced no significant change in nighttime
      pineal or serum melatonin levels, as compared to controls, nor did it
      significantly influence levels of pontine medullary 5-hydroxytryptamine [5-HT]
      and hypothalamic 5-hydroxyindoleacetic acid [5-HIAA]. Placing rats in a 7-Tesla
      MRI magnet for 45 minutes produced similar results. CONCLUSIONS: These
      experiments suggest that daily light/dark cycle has much greater influence on
      levels of melatonin, catecholamines, serotonin, or their metabolites than does
      exposure to a static magnetic field.

PMID- 9190702
TI  - Flies with many eyes: first master gene found.

PMID- 9190703
TI  - The falling sickness arises.

PMID- 9190704
TI  - On the past of Hungarian neurosurgery and its present state: a typical east
      European story(?).

PMID- 9190705
TI  - Is there a disease afflicting neurosurgeons worldwide?

PMID- 9190706
TI  - [Venous leg ulcers].

PMID- 9190707
TI  - [Imported diseases].

PMID- 9190708
TI  - [Why does the prostate grow? Possible role of growth factors for development of
      benign prostatic hyperplasia].

PMID- 9190709
TI  - [Venous leg ulcer].
AB  - The article summarizes current views regarding venous leg ulcers. Venous ulcers
      are resource-demanding and affect 1% of the population. Superficial and/or deep
      venous insufficiency is to be found combined with perforator insufficiency in the
      ankle are. The pathogenesis is still open to debate, but is presumably related to
      capillary leakage, with seepage of blood components and ensuing
      lipodermatosclerosis, as well as to multiple capillary thromboses. Inappropriate
      leucocyte activation might also play a part. Compression stabilizes capillary
      function and thus is the cardinal treatment both regarding healing and
      prophylaxis. In 90% of cases there is no recurrence following superficial vein
      surgery, so long as the deep veins remain unaffected. In patients with deep
      venous insufficiency the risk of failure following-such surgery, perforator
      resection included, is related to the degree of insufficiency. If conventional
      treatment fails, reconstruction of the deep veins may be considered. Concomitant
      conditions such as arterial insufficiency and systemic diseases make treatment
      difficult, and the presence of Pseudomonas aeruginosa may in certain cases delay
      healing.

PMID- 9190710
TI  - [Surgical wound infections--have we achieved all that is possible?].
AB  - There is still a solid foundation for a further reduction of surgical wound
      infections. Every twentieth surgical bed is occupied by a patient with this
      complication. Though three out of four wards register the infections, serious
      problems with the methods have been established. Thus, it would not be
      justifiable to use the current registrations for monitoring for clinical and
      administrative purposes. Death or serious health consequences are to many
      patients the reality after a wound infection; the social and economical costs are
      also important. Better systems for surveillance of infections or complications
      must be developed specifically for the Danish hospitals. The hygienic expertise
      must be strengthened. Increased resources based on long-term planning are
      required to prevent more wound infections. Hospital hygiene will be a suitable
      subject for quality improvement. The surgical specialties should be encouraged to
      settle standards for specific procedures as to acceptable levels of infection.

PMID- 9190711
TI  - [Group homes for the mentally ill I. A description of access and residents].
AB  - In a cross-sectional study, we assessed social and psychiatric characteristics of
      71 residents in the group home programme for the mentally ill in Copenhagen. The
      majority suffered from long-term functional or organic psychosis, dominated by
      anxiety and residual symptoms of schizophrenia. Social functioning was impaired
      to a moderate degree. Emotional and social support were among the main functions
      of the staff. More than 60% regarded the group home as a temporary residence, but
      the length of stay varied between a few months and 5.7 years. All residents were
      treated in the local outpatient psychiatric service. This type of housing support
      should be regarded as an important part of a comprehensive community care
      service.

PMID- 9190712
TI  - [Group homes for the mentally ill II. Resident satisfaction and experience of
      support].
AB  - The aim of this cross-sectional study was to evaluate aspects of user
      satisfaction and subjective change in functional status of 71 long-term mentally
      ill group home residents in Copenhagen. Satisfaction rate varied between 52 and
      89%, and though distress caused by fellow residents was seen in 76%, around 80%
      also experienced some degree of reciprocal supportive relationship with the
      others. More than half of the residents would prefer to live alone, with a
      partner or a friend. General life satisfaction was improved in 72%, and improved
      status within various life domains was reported in 32-78%. The group homes
      represent a large potential for improving functional status in the severely
      mentally ill.

PMID- 9190713
TI  - [Occurrence of hepatitis A infection in Denmark].
AB  - Hepatitis A is a mandatory notifiable disease in Denmark. The number of notified
      cases of hepatitis A was compiled over a period of 16 years, 1980-1995. A total
      of 3790 were included in the study. The average incidence was 4.6 per 100,000
      population per year, but the number of cases declined slightly through the
      period. Median age among Danes were 27 years and among immigrants seven years.
      The male to female ratio was 1.5 among Danes and 1.1 among foreigners. The
      incidence was highest in the capital area. Two-thirds of the notified persons
      were infected in Denmark, among whom the source of infection was unknown for half
      of the cases. The two most important sources of infection were household
      contracts and i.v. drug abuse. A total of 73 persons were infected in connection
      with their occupation in Denmark. Workers in day care centres, sewage workers and
      cleaners may be particularly at risk, although the risk is still low. The
      relevance of vaccination recommendations for special groups is considered.

PMID- 9190714
TI  - [Breaking bad news--experience and attitude of young physicians].
AB  - This survey reports the attitude among second year medical doctors towards giving
      patients bad news. The questionnaire contained a mixture of open and closed
      questions. The questionnaire was returned by 88/119 (74%). All doctors felt that
      a patient who suffers from a serious, incurable disease has the right to be told
      the diagnosis, 98% of the doctors had broken bad news-most of them had done it
      several times. More than 90% of the doctors judged that their knowledge
      concerning breaking bad news, communication and crisis- and grief-reactions was
      average or above, but less than 10% thought that their knowledge was adequate.
      All the responders wanted instructions on how to break bad news, but only 45% had
      received some.

PMID- 9190715
TI  - [Frequency of infections after shunting of hydrocephalus. An analysis of 884
      shunts].
AB  - Postoperative infections are major complications to cerebrospinal fluid (CSF)
      shunting in the treatment of hydrocephalus and other conditions with impeded CSF
      transportation. In a retrospective study 884 first-time shunts inserted in the
      years 1958-1989 are investigated. Infection rate is studied including influence
      of following variables: time period, age of patient, education of neurosurgeon,
      length and time of operation and placement of the distal drain. Overall infection
      rate for all implanted CSF shunts is 7.4% (5.7-9.3%) and acute rate of infection
      is 6.2% (4.6-7.9%). Rate of infection is virtually constant for all variables
      except education of the neurosurgeon. Neurosurgical trainees have significantly
      higher infection rates. Use of prophylactic antibiotics is still controversial No
      prospective, double blinded studies including sufficient number of patients to
      evaluate this issue exist today. Meta-analysis studies conclude that use of
      prophylactic antibiotics is associated with a significant reduction in subsequent
      CSF shunt infection. We recommend that shunt implantation primarily be performed
      by highly trained neurosurgeons and that there should be increased supervision
      during CSF shunt operations performed by neurosurgical trainees.

PMID- 9190716
TI  - [Giant cell arteritis, temporal arteritis. A quality assurance project of medical
      records, biopsies and histological assessment].

PMID- 9190717
TI  - [Cat-scratch disease--an overlooked disease in Denmark?].
AB  - Only one patient with cat-scratch disease (CSD) has been reported in Denmark. A
      case and retrospective investigation among patients admitted to the ward is
      presented. Over a period of 3.5 years, six patients were found to have suffered
      from CSD. The yearly incidence was calculated to 2.6/100,000. The patients were
      tested for antibodies against Bartonella (Rochalimaea) henselae with a new test
      developed at the Danish Serum Institute. Only two of the patients with CSD had
      titres of antibodies higher than 400 (positive). Tested again with an improved
      test five of the six patients were found to have antibodies against B. henselae.
      It is assumed that CSD is found with the same incidence as the USA and Holland.
      It is recommended that examination for chronic lymphadenopathy includes questions
      about cat contact and testing for antibodies against Bartonella henselae.

PMID- 9190718
TI  - [Nitric oxide treatment of children with impairment of oxygenation].
AB  - It is well-known that inhaled nitric oxide improves the perfusion of ventilated
      regions, thus reducing intrapulmonary shunting and improving arterial
      oxygenation. However, most cases describe treatment of neonates and adults, only
      few studies describe effects of inhaled nitric oxide in children with severe
      impairment of oxygenation. Four cases of severe hypoxaemic respiratory failure in
      children treated successfully with inhaled nitric oxide are described.

PMID- 9190719
TI  - [Use of cellular telephones and automobile driving].

PMID- 9190720
TI  - [Hearing on research quality and continuing education, Wednesday, 19 March 1997].

PMID- 9190721
TI  - [Injuries caused by vibrating equipment].

PMID- 9190723
TI  - [Gastroscopy in children].

PMID- 9190722
TI  - [Acute water intoxication caused by intranasal desmopressin--Minirine].

PMID- 9190724
TI  - [Nuclear medicine].

PMID- 9190725
TI  - [Dementia].

PMID- 9190726
TI  - [Prognosis in hepatic steatosis].

PMID- 9190727
TI  - [Uncomplicated gallstones: who should be operated on?].
AB  - Gallstones are common and occur asymptomatically or symptomatically with or
      without complications. Treatment is only required for symptomatic gallstones and
      complications in gallstones. Laparoscopic cholecystectomy is the treatment of
      choice for symptomatic gallstones and is performed with an increasing frequency.
      One may fear, that the indications for cholecystectomy have changed, and surgery
      is now undertaken for a lesser degree of morbidity. Cholecystectomy does not
      increase life expectancy, and 20-30% of patients cholecystectomized for
      symptomatic gallstones complain of abdominal pain of unknown origin after the
      operation. New valid parameters in order to predict which patients will benefit
      from cholecystectomy are therefore necessary. Symptoms specific to gallstones are
      not precisely known, and greatest success in treatment seems to be related to the
      occurrence of severe, often steady pain, of hours' duration, often located in the
      epigastrium or upper right quadrant, with or without radiation and/or vomiting.
      Dyspepsia alone is not an indication for cholecystectomy. Psychological
      vulnerability may predict a poor outcome after cholecystectomy and should lead to
      reconsideration of the indication for surgery.

PMID- 9190728
TI  - [Marked increase in incidence of non-Hodgkin's lymphoma among young people in
      Denmark during 1943-1989].
AB  - Time related trends in incidence of non-Hodgkin's lymphoma in Denmark in the
      period 1943-1989 were analysed. A total of 13,822 patients were included in the
      study. World standardized incidence rates per 100,000 population increased from
      2.5 in men and 1.9 in women in 1943-1947 to 9.3 in men and 6.5 in women in 1988
      1989. Trends in age-specific incidence were analysed for two periods, i.e. 1943
      1977 and 1978-1989. In both periods, the incidence of NHL increased in all age
      groups. In general, the rate of increase was higher in the recent period, with
      the exception of the oldest age-group among whom the incidence increased by 7%
      annually between 1943 and 1962. In recent years an increase in incidence
      averaging 8% annually was observed in men and women aged 40 to 49 years. The
      remarkable and parallel time trends observed in young men and women in recent
      years indicate that factors other than AIDS must be contemplated.

PMID- 9190729
TI  - [Survival in ovarian cancer treated in a gynecological department of a central
      hospital].
AB  - The characteristics of 73 patients with all stages of epithelial ovarian cancer
      were retrospectively analysed with emphasis on prognostic factors and survival.
      The patients underwent total hysterectomy, bilateral oophorectomy and infracolic
      omentectomy. Efforts were made to reduce the tumor burden as much as possible
      without endangering the general health status of the patient. Postoperative
      treatment was cisplatin 60 mg/m2 body surface and cyclophosphamide 50 mg/m2 every
      four weeks (CP). Patients with low general health status were offered either
      treosulphane 1 g daily for four weeks alternating with four weeks without
      treatment, or no treatment. Patients in FIGO stage IA and B generally received no
      postoperative chemotherapy treatment. Fifteen percent were in FIGO stage I, 7% in
      stage II, 5% in stage III and 23% in stage IV. Fifteen patients could be
      radically operated, however, only three patients who were in stage III. Fifty
      four patients were treated with CP, 11 with treosulphane and eight patients did
      not receive postoperative treatment. In 28 patients second look laparotomy was
      performed. Only six patients had a complete pathological response, two of these
      in stage III. Stage and tumour grade could be identified as prognostic factors.
      Three-year survival was 70% in stage I, 67% in stage II, 28% in stage III and 0%
      in stage IV. Survival in 43 patients in stage III and IV was statistically
      compared to 265 patients from a prospective, randomized study by the Danish
      Ovarian Cancer Group (DACOVA), comparing cyclophosamide and cisplatin with and
      without doxorubicin. We found no statistical difference in survival between
      patients in our material and the DACOVA-material except in patients with low
      grade tumours whose survival in the CAP-arm of the DACOVA-study was superior. The
      rate of complete pathological response was significantly better in the DACOVA
      study.

PMID- 9190730
TI  - [Microalbuminuria as predictor of atherosclerotic cardiovascular disease in
      IDDM].
AB  - The aim of this follow-up study was to assess whether slightly elevated urinary
      albumin excretion, i.e., microalbuminuria, precedes development of
      atherosclerotic vascular disease in IDDM. Out of 259 IDDM-patients 30 developed
      vascular disease during 2,457 person-years. Microalbuminuria was significantly
      predictive of vascular disease (hazard ratio (95% confidence interval) 1.06 (1.02
      1.18) per 5 mg/24 hours increase in urinary albumin excretion; p = 0.002). The
      predictive effect was independent of age, sex, blood pressure, tobacco smoking,
      serum concentrations of total-cholesterol, HDL-cholesterol, sialic acid, and von
      Willebrand factor, and of haemoglobin A1c, insulin dose, diabetes duration, and
      diabetic nephropathy (hazard ratio (95% confidence interval) 1.04 (1.01-1.08) per
      5 mg/24 hours increase in urinary albumin excretion; p = 0.03). It is concluded
      that slightly elevated urinary albumin excretion is an independent predictor of
      atherosclerotic vascular disease in insulin-dependent diabetes mellitus.

PMID- 9190731
TI  - [Esophago-gastro-duodenoscopy of pediatric patients].
AB  - In total 199 oesophago-gastro-duodenoscopies (OGD) were performed in 71 female
      and 71 male paediatric patients (three months-15 years, median 8 years 2 months).
      The endoscopy was performed in general anaesthesia in children less than five
      years old, and in an intravenous sedation in older patients. The indications for
      OGD were: recurrent abdominal pain and concomitant positive antibodies against
      Helicobacter pylori as a part of a scientific project, upper dyspepsia, upper
      gastrointestinal bleeding, failure to thrive, coeliac disease, suspicion of
      chronic inflammatory bowel disease and a percutaneous gastrostomy. Seventy-two
      OGD were carried out in general anaesthesia, 86 in intravenous sedation with
      midazolam and pethidine and 41 in intravenous midazolam sedation. Complications
      related to the sedation or to the endoscopy were not observed. Amnesia was
      reported in 94/95 children who were sedated intravenously with midazolam and
      pethidine or midazolam alone. Six endoscopies could not be carried out in
      intravenous sedation because of agitation. In the primary OGD endoscopy revealed
      a normal mucosa in 121/142 (85%), oesophagitis in four (3%), nodular mucosa in
      six (4%), gastritis in four (3%) and a duodenal ulcer in one (0.7%). Histology
      disclosed active or inactive chronic gastritis at the primary endoscopy in 35/69
      (51%) of the children with recurrent abdominal pain and antibodies against H.
      pylori. In children with failure to thrive an avillous duodenal mucosa was seen
      in 3/32 (9%). A comparison between histological and stereomicroscopical
      evaluation of the duodenal biopsies revealed agreement in 41/47 (87%). We
      conclude that OGD is a safe and tolerable procedure in paediatric patients, in
      whom possible morphological changes are suspected. The indications for an OGD
      need further evaluation.

PMID- 9190732
TI  - [CT of primary cerebral lymphoma in non-immunosuppressed patients].
AB  - In the last 10-15 years primary lymphoma of the brain has tripled in frequency in
      the non-immunosuppressed population. The correct diagnosis by CT-examination is
      difficult as primary lymphoma imitates different pathological conditions. Five
      examples from a series of 13 patients are presented.

PMID- 9190733
TI  - [Alzheimer's disease precipitating mutations in presenile genes result in
      increased production of amyloid peptide A beta(42)].

PMID- 9190734
TI  - [CT and MR scanners].

PMID- 9190735
TI  - [Pneumococcal vaccination and diabetes].

PMID- 9190736
TI  - How not to give a lecture.

PMID- 9190737
TI  - ["Magic triangle": patient competence--living will--legal guardianship].

PMID- 9190738
TI  - [Accident incidence at various ages].
AB  - The number of accidents happening at different stages of life is dependent on
      many factors. While most accidents caused by drivers in their early adult life
      result from a lack of experience and overestimation on their own skills,
      illnesses and physiological deficiencies brought about by old age account for an
      ever increasing percentage of the accidents caused by old drivers. These changes
      in the state of the health of old drivers that are potential causes of accidents
      are not reflected by official accident statistics and can therefore only be
      described according to their risk potential. Surveys among individual risk groups
      or certain groups of patients show that various health problems lead to a much
      higher risk of accidents that can be seen from the statistics. The increasing
      number of relatively old people that are in possession of a driving licence will
      have a large-scale effect on insurances, damage calculations and possibly make
      regulating measures necessary also for experienced drivers similar to the system
      of restricted driving licence introduced in Germany where beginners have to prove
      their driving ability over a period of two years.

PMID- 9190739
TI  - [Typical sports injuries, sports specific risks and comparison with other sources
      of accidents].
AB  - In the discussion of limiting the growth of medical spending there are intentions
      to exclude the costs of sport injuries from coverage by the public health
      insurance system. The aim of this study is to analyse typical sport injuries and
      to compare them with injuries from other fields of accidents and thus to deliver
      arguments in the discussion of costs in public health system.

PMID- 9190740
TI  - [Fatal post-traumatic alcohol delirium--compensation responsibility in private
      accident insurance?].
AB  - While several case reports about fatal posttraumatic alcohol withdrawal deliriums
      after minor traumas and compensation by legal insurance have been published this
      problem has been hardly addressed regarding private accidance insurance. Based on
      the very comprehensive definition of an accident in the private insurance law
      posttraumatic deaths by alcohol withdrawal deliriums can be causally related even
      to minor traumas and compensations by private insurance are justified. However
      according to section 8 AUB 88 the contribution of preexisting alcoholism and
      alcohol related organ damage to the lethal outcome must be subtracted.

PMID- 9190741
TI  - [Detection of so-called "cervical whiplash trauma"].
AB  - For the evidence of causality of an accident for a cervical injury without any
      contact with the interior, it is necessary to provide a interdisciplinary
      expert's opinion. According to the state of experts knowledge for reconstruction
      of accidents a slight cervical injury can be precluded if the alteration of speed
      of the pushed car ist less than 15 km/h. Medical diagnoses are only valid if they
      have been proved by objective results. A diagnose based only on a subjective
      information is to be considered as a suspicious diagnose.

PMID- 9190742
TI  - [Geriatric orthopedic treatment of Jehovah's Witnesses?].
AB  - The proceedings in elective surgery on "Jehova's Witnesses" differ from customary
      operations. Intensive physical therapy, high complaint, internal and
      anesthesiologic examination, exact information about the risks and facilities as
      "cell-saving" etc. and postoperative planing are necessarily required ahead of
      the indication to operate. Additional complications may be possible. The higher
      costs are balanced by avoiding, respectively getting rid of disability,
      immobilisation and the needing of care. A religious dogma leads to a special
      point of view towards life, death, health and expectations towards' the life and
      its quality as well as social support. It is a difficult undertaking in elective
      surgery to bring this dogma and our ethic and moral values into accord. It is not
      medicine vs. religion, but to point out a way and the limits by respecting the
      individual ideology, abstract conceptions and philosophy of life.

PMID- 9190744
TI  - [Comment on A Regenauer: Prognostic aspects of the metabolic syndrome].

PMID- 9190743
TI  - [Traumatic splenic rupture--fatal increase in thrombocytes after splenectomy].
AB  - A patient with CMGM developed after traumatic splenectomy a severe thrombocytosis
      up to 4 millions. 25 days after the accident he died of acute right heart failure
      caused by vascular occlusion of lung vessels due to thrombocyte aggregations.
      According to the regulations of professional cooperatives in Germany the death is
      caused by the occupational accident. A bereaved pension will be payed. For the
      private life insurance the blood disease is with 33% partial responsible for the
      fatal development and reduces the payment. According to german penal law the
      death of the victim will tighten the punishment, if someone else is guilty for
      the accident. A professional error on the part of a doctor is not provable.

PMID- 9190745
TI  - [The combined prevention of meteoropathological reactions in patients with
      circulatory encephalopathy].

PMID- 9190746
TI  - [Thermal vibromassage in the treatment of children with dyskinesia of the biliary
      tract].
AB  - Combined use of tubage with 2% solution of natural agent Shirsal and
      thermovibromassage of the right hypochondrium area for biliary dyskinesia
      promotes normalization of biliary system motility. The course of the procedures
      enhances the positive clinical trend and induces remission which persists for 6-8
      months.

PMID- 9190748
TI  - [The combined use of mud applications and the drinking of carbonate mineral water
      in patients with gastric and duodenal peptic ulcer].

PMID- 9190747
TI  - [The effect of the combined use of mineral water and rutin on the function of the
      adrenal cortex and pancreatic islet apparatus (an experimental study)].
AB  - Before modelling of experimental ulcer according to I. S. Zavodskaia the animals
      (157 male Wistar rats) were given for 24 days mineral water Essentuki N 17 and
      rutin in a dose 20 or 40 mg. Those given 20 mg of rutin in combination with
      mineral water demonstrated a higher rise in blood concentrations of
      hydrocortisone, insulin and thyroxine. Gastric mucosa and levels of serum alpha
      1, alpha-2, beta-globulins and albumins were less damaged.

PMID- 9190749
TI  - [Galvanization of the liver in the prevention of cholelithiasis in patients with
      chronic cholecystitis].
AB  - It is shown in 22 patients with chronic noncalculous cholecystitis that hepatic
      exposure of such patients to constant current changes chemical composition of
      bile components in such a way that bile lithogenic characteristics make formation
      of choleliths less probable.

PMID- 9190750
TI  - [The mechanism of action of low-intensity laser radiation].
AB  - The authors review primary mechanisms of action of low-intensity laser radiation
      used in physiotherapy. The hypothesis suggested by the authors allows one to
      compare efficacy of bioenergetic action of electromagnetic radiation varying in
      ranges, of therapeutic lasers, in particular. However, animal experiments have
      shown greater than bioenergetic action efficacy of the mechanism used by the
      nervous system in response to laser radiation.

PMID- 9190751
TI  - [Swimming as a means of enhancing the adaptive potentials of the disabled after
      amputation of the lower extremities].
AB  - The studies of adaptive-compensatory reactions in low-limb amputees on training
      swimming regimens registered changes in vegetative regulation, predominance of
      the sympathetic component, low cardiovascular adaptive potential. High
      amputations led to arterial hypertension. Swimming and underwater exercise
      suppressed the influence of the sympathetic component of the autonomic nervous
      system, promoted enhancement of automatic regulation of the cardiac rhythm,
      lowering of arterial pressure. Pool exercise are recommended for rehabilitation
      of amputees.

PMID- 9190752
TI  - [Information network systems].

PMID- 9190753
TI  - [The reaction of the cardiovascular system to terrain cure in patients with
      ischemic heart disease who have undergone surgical myocardial revascularization].
AB  - Muscular training in IHD patients who have undergone surgical revascularization
      of the myocardium should be planned on the individual basis regarding functional
      condition of the cardiovascular system. Patients with reduced left ventricular
      contractility should exercise under Holter ECG monitoring to control episodes of
      ventricular arrhythmia.

PMID- 9190754
TI  - [The organization of the rehabilitation of children from ecologically unhealthy
      territories].

PMID- 9190755
TI  - [A self-contained unit for preparing and performing dry-air radon baths].

PMID- 9190756
TI  - [The dynamics of the autonomic indices during the health resort treatment of
      children who live in areas contaminated by radiation].

PMID- 9190757
TI  - [The problems and paths of development in clinical physiotherapy].

PMID- 9190758
TI  - [Physiotherapeutic prescribing in gynecological practice (a short guidebook)].

PMID- 9190759
TI  - [The use of sodium chloride baths in children with a heart lesion subjected to
      long-term exposure to low radiation doses].
AB  - Children exposed to low-dose radiation are often treated in sanatoria with
      mineral baths. Of the latter balneoprocedures widely practiced are sodium
      chloride (SC) baths with mineralization 20-30 g/l. Mineralization 40 g/l is less
      frequently used. To specify changes in the function of cardiovascular system
      induced by SC baths of different concentration (40 versus 20 g/l) 131 senior
      schoolchildren exposed to low-dose radiation or other environmental pollutants
      were examined both after a single balneological procedure and after the course
      treatment (maximum 10 procedures). The baths lasted 8-15 min at water temperature
      36-38 OC in a day intervals. The response was assessed by ECG, tetrapolar chest
      rheography, bicycle exercise. All the children had cardiovascular disorders of
      non-rheumatic origin. Therapeutic effect was more pronounced after baths with SC
      concentration 40 g/l. These baths are recommended for improvement of vegetative
      regulation of the heart, correction of hemodynamic defects. Baths with
      mineralization 20 g/l are better in upgrading function of the autonomic nervous
      system.

PMID- 9190760
TI  - [Educational programs for hypertension patients and their realization under
      sanatorium-health resort conditions].

PMID- 9190761
TI  - [The immunomodulating effects of low-intensity laser radiation].

PMID- 9190762
TI  - [Outstanding Moscow specialists in health resort medicine V. A. Aleksandrov (1877
      1956) and G. M. Danishevskii (1890-1971)].

PMID- 9190763
TI  - [Treatment by Schrott's method in the health resorts of Austria and Germany].

PMID- 9190764
TI  - [Prognostic criteria of the efficacy of magnetic and magnetic-laser therapy in
      patients with the initial stages of hypertension].
AB  - Study of the efficacy of a course of exposures to travelling pulsed magnetic
      field and magnetic laser sessions in 97 patients with stages I-II essential
      hypertension showed a high efficacy of travelling pulsed magnetic field in
      patients with hyperkinetic hemodynamics and initially just slightly shifted blood
      rheology and platelet hemostasis. Magnetic laser therapy is more effective in
      patients with eukinetic and hypokinetic hemodynamics and initially sharply
      expressed disorders of blood rheology and platelet hemostasis.

PMID- 9190765
TI  - [Pharmacological therapy in erectile dysfunction--current standards and new
      viewpoint].
AB  - Intracavernous pharmacotherapy of erectile dysfunction has been established for
      over 10 years, with prostaglandin E1 (PGE1) being the standard substance with the
      lowest rate of side effects. Recent investigations deal with the identification
      of intracellular mechanisms of smooth muscle relaxation in cavernous tissue as
      the most important aspect of penile erection. Nitric oxide and specific
      phosphodiesterase-isoenzymes seem to play a central role. This resulted in
      clinical studies with the intracavernous injected nitric oxide-donor linsidomine
      (SIN 1) and the orally given phosphodiesterase-inhibitor sildenafil. Furthermore
      new ways of pharmaco-application are tested, e.g. transdermal treatment with
      nitroglycerin, minoxidil or papaverine, as well as intraurethral injection of
      prostaglandin E1.

PMID- 9190766
TI  - [Psychological aspects of erectile dysfunction].
AB  - It is widely accepted opinion that male sexuality comprises more than an erected
      penis. This fact should be considered in the management of erectile dysfunction.
      Therefore, the valuation of sexual disturbances have to be essentially included
      in the general examination programme of erectile impotence. Several causes are
      known to contribute to an erectile dysfunction. The anamnesis can be taken as an
      important tool for classification of the erectile dysfunction. The following
      questions are helpful in the clinical practice: erectile dysfunction during
      sexual intercourse only but also during masturbation; spontaneous erections;
      dependence of the erectile impotence on special situations, partners and events;
      questions for somatic and psychosocial risks. Sexual therapy represents a complex
      intervention will be aim of improvement of the functional disturbances in
      consideration of the general risks for sexual impairments.

PMID- 9190767
TI  - [2 dictionaries--on disks: the CD-ROM publication of Roche Lexikon Medizin and of
      the clinical thesaurus].

PMID- 9190768
TI  - [Therapy of male subfertility].
AB  - The possibilities of treating male subfertility are still limited. Approaches at
      medical therapy include stimulation of spermatogenesis at the testicular level,
      improvement of epididymal function (sperm maturation), influence on sperm
      transport and activation of sperm metabolism with improvement of sperm motility.
      Causal therapy has been most successful in patients with hormonal insufficiency
      and male adnexitis, while microsurgical reconstructive measures have yielded best
      results in cases of occlusion within the efferent seminal ducts. New therapeutic
      approaches include the use of mast cell blockers and alpha blockers as well as
      vitamin C/E as an antioxidative treatment to reduce reactive oxygen species. If
      medical or surgical therapy has failed, methods for improvement of sperm quality
      in vitro must be considered (swim-up technique, glass wool filtration,
      migration/sedimentation technique, density gradient centrifugation). In cases of
      severe male sterility factor, intracytoplasmic sperm injection (ICSI) has been a
      breakthrough in the therapy of childlessness. A further progress is the
      collection of spermatozoa from the epididymis (MESA = microsurgical epididymal
      sperm aspiration) or testis (TESE = testicular sperm extraction). Finally,
      pressure in terms of time and organization can now be avoided by the use of
      cryopreserved spermatozoa from the ejaculate, epididymis or testicular tissue so
      that microinjection may be planned independently of the partner. In any case, a
      close cooperation between gynecologist and andrologist is of utmost importance.

PMID- 9190769
TI  - [Spermiogram findings following antegrade sclerosing of a varicocele].
AB  - Antegrade scrotal sclerotherapy is an established method for treatment of
      varicocele. Semen analysis of 103 patients at least 6 months postoperatively
      showed an significant increase of progressive motility from 36.5 +/- 20.7% to
      51.7 +/- 20%. Evaluation of sperm density and morphology showed a significant
      increase too. In 79% we found an improvement of sperm density, in 63% of normal
      morphology and in 71% of progressive motility. There was no correlation between
      preoperative size of varicocele to postoperative findings in semen analysis. In
      42% (n = 38) of inability to conceive the partners became pregnant. These results
      show that antegrade scrotal sclerotherapy is equivalent to other kinds of
      operative treatment for varicocele with regard to improvement of fertility
      parameters.

PMID- 9190770
TI  - [Current aspects of hormone diagnosis in andrology--predictive values for the
      preservation of spermatogenesis].
AB  - The occurrence of hormonal disorders in 1.4 to 9.7% of the patients of andrology
      units justify a corresponding hormone analysis. Besides helping to make the
      differential-diagnosis of a disease hormone results are important for the
      description of preservation of spermatogenesis in cases of aspermia or
      azoospermia. Indications of a rest-spermatogenesis or a spermatozoon-pool could
      be crucial for assisted reproduction. Spermatological and testis-histological
      data of 2 independent collectives (n1 = 138; n2 = 110) were correlated with basal
      levels of FSH, LH, PRL, T, free T, and E2. Serum FSH appears with a sensitivity
      of 88.8% and a specification of 94.1% as good, but not absolutely certain
      discriminator of preserved or disturbed spermatogenesis. The inclusion of testis
      volume improves the diagnostic reliability only negligibly--the critical size is
      16 ml. Because of its low diagnostic sensitivity the serum LH alone gives not
      much information but it can indicate together with serum testosterone causally
      relevant disorders in androgen metabolism (i.e. androgen resistance syndrome.
      Klinefelter-syndrome). PRL, T, free T, and E2 gave no conclusion of occurrence of
      disturbed or preserved spermatogenesis. For indication of performing testis
      biopsy because of diagnosis and therapeutic considerations further factors of
      spermatogenesis are required.

PMID- 9190771
TI  - [Intracytoplasmic sperm injection--importance and challenge].
AB  - The male factor is going to be one of the major problems in the treatment of
      infertility. In addition to the standard methods of assisted reproduction new
      microtechniques of assisted fertilization have been developed to increase success
      rate in cases of male factor infertility. Of these methods especially
      intracytoplasmatic sperm injection (ICSI) has been described as beneficial in
      which one spermatozoa is injected directly into oolemma of an oocyte. ICSI can be
      carried out with ejaculated spermatozoa, with epididymal spermatozoa and with
      spermatozoa isolated from a testicular biopsy. In all cases high fertilization
      and pregnancy rates comparing with standard in-vitro fertilization were achieved.
      It may be recommended that the couples undergo prenatal diagnosis and participate
      in a prospective follow-up study of children born after ICSI. In management of
      ICSI all specialists in gynecology, embryology, andrology, medical genetics and
      urology should go together.

PMID- 9190772
TI  - [Ethical questions and marginal problems in assisted reproduction].
AB  - Assisted reproduction is subject of ethical controversies as it depends very much
      on our understanding of both the human being and of individual dignity. The
      ethical and technical boundaries have changed very much over the last decades.
      The main focus of the debate until the eighties was to avert manipulation and
      hazards to human health (surrogate mothers, chimeras). Speculations which
      exceeded the real possibilities of biomedicine were common. Finally the
      technology was restrained by an ethical and legal framework: in Germany the
      parliament passed the "Embryo protection act" (Embryonenschutzgesetz). Since the
      beginning of the nineties the focus of ethical problems has shifted towards the
      legal overregulation, which is in fact hampering the application of helpful and
      humane technology, like for instance preimplantation diagnosis. Ethical
      discussion and analysis should be directed at regulations that promote the
      dignity of the individual as well as the search of consensus positions, which can
      live up to the realities of a pluralistic society.

PMID- 9190773
TI  - [Is there a renaissance of conservative therapy in plastic penile induration?].
AB  - The management of Peyronies's disease should include an exact pretherapeutic
      staging. Diagnostic methods like ultrasound imaging, X-ray using "mammography
      technique" and magnetic resonance imaging are modalities of choice. The good
      results of new conservative therapy options have to be evaluated in randomized
      multicentric studies. Surgical therapy shows good results in patients with
      calcified plaques.

PMID- 9190774
TI  - [Population growth and public health: a complementary consideration].

PMID- 9190775
TI  - [Temporary medicosocial admission: alternative to hospitalization of elderly
      persons?].
AB  - The orientation of elderly patients, temporarily disabled, to acute care beds is
      inappropriate because of its adverse effects on functional status and its costs.
      The creation of short-stay units (SSU) in nursing homes provides an alternative
      to acute care hospitalization. The aim of this retrospective study, involving the
      first 64 patients oriented to the SSU from the emergency center, was to evaluate
      this new health care network. The analysis was focused on the rate of appropriate
      orientation (site of living at four month; subsequent medical events), as well as
      the functional quality of this health care network. Information were collected
      from medical records of the 64 patients oriented to SSU and 64 sex- and age
      matched patients admitted during the same period, and the opinion of the
      network's partners. The mean age of patients and controls was 82 years. Four
      months after admission to the SSU, the orientation was considered appropriate in
      58% of the cases (living at home without subsequent hospitalization), doubtful in
      8%, and inappropriate in 33%; 27% of patients and 13% of controls were living
      definitely in nursing homes (p < 0.1). No medical or social characteristics was
      correlated to inappropriate orientations. In conclusion, the creation of SSU may
      be considered as an improvement in the care of elderly patients. The main problem
      of this orientation was the high percentage of patients living permanently in a
      nursing home four months later. Accurate assessment's tools capable to predict
      the subsequent decrease of the functional status should be used in the daily
      practice in order to improve the orientation of elderly patients.

PMID- 9190777
TI  - [Income, health, and health services utilization in Germany 1992].
AB  - Data from the 1992 wave of the Socioeconomic Panel were used to analyse the
      relation between incomes, need for and utilisation of health care in East- and
      West Germany employing methods coming from the economic measurement of income
      distributions. "Self assessed health" and "restricted activities of daily living"
      were employed as need indicators. Utilisation was measured by the number of
      "visits to physicians" and "days in hospital". Data was available for 6435
      individuals (west) and 3928 individuals (east). Income was defined as equivalent
      net household income with an equivalence scale derived from the german social
      assistance program. Compared to the concentration of income all variables in the
      scope of this study were only marginally concentrated (i.e. equally distributed).
      A slight concentration of need amongst the lower income was overcompensated by
      utilisation. Thus a very small impact of the German health care system favouring
      lower income individuals was measured. The study shows methodological problems
      when combining data from regions with strongly different income levels instead of
      analysing them separately. A combined analysis tends to underestimate
      concentration.

PMID- 9190776
TI  - [HIV prevention in Turkish immigrants in a general internal medicine outpatient
      service].
AB  - This study investigates the level of knowledge about mechanisms of HIV
      transmission and risk behaviour for HIV infection in Turkish immigrants in Basel,
      Switzerland. In addition, the effectiveness of physician based HIV counseling in
      a general internal medicine outpatient clinic was evaluated. Two consecutive
      samples of 150 and 98 Turkish patients with a first clinic contact, were
      recruited 6 months apart. The first group was exposed to an interpreter assisted
      counseling on HIV prevention (intervention group), the control group received no
      systematic counseling. Knowledge about mechanisms of HIV transmission and risk
      behaviour for HIV infection was assessed by a 29 item questionnaire at baseline
      and by interview at follow-up. One year follow-up was possible in 49% of the
      patients. At baseline, Turkish patients had statistically significant lower
      global scores on knowledge about HIV than a second control group of 148 Swiss
      patients. Mean percentage scores of correct answers in the whole Turkish study
      population improved from 49.3% to 60.0% (p < 0.0001). However, the difference of
      gained knowledge between intervention and control groups was only of borderline
      significance (p = 0.059). Study design and low follow-up limit conclusions from
      this study. From 1992 to 1994 knowledge about HIV infection had improved in
      Turkish patients, but was still inferior to the knowledge of Swiss patients.

PMID- 9190778
TI  - [Educational strategies and tools in a public health program at the University of
      Geneva].
AB  - In the Swiss context, the newly developed MPH programme at the University of
      Geneva is experimental in educational matters. Indeed the programme is fully
      learner-centered and community-oriented. Throughout the curriculum students plan,
      implement and evaluate intervention programmes or/and research projects related
      to health problems of the communities they are in charge of. In this article, we
      describe the educational strategies and tools used in this MPH curriculum
      (professional profile, mind-mapping procedures, field-work either on research
      projects or on intervention programmes, group work and evaluation procedures).
      These strategies and tools might assist some educational experimentation in MPH
      programmes in search of public health relevance and pedagogic efficacy.

PMID- 9190779
TI  - [Evaluation of methods for preparing chicken feces from the veterinary hygienic
      aspect].
AB  - Fresh and dried faeces of laying hens from battery fattening and faeces from
      complete confinement rearing were investigated with bacteriological and physico
      chemical methods. The comparison shows that ventilated faeces from conveyor belts
      with significantly higher values of the autochthonous faecal flora (endogerms,
      coliform germs, faecal streptococci) are most unfavourable from an
      epidemiological-bacteriological point of view. Salmonellae occurred very
      frequently both in fresh faeces (in 76.9% of the samples) and in ventilated
      faeces from conveyor belts (in 83.9% of the samples), whereas this agent was only
      detectable in 1.9% of the samples of faeces from complete refinement rearing.
      Fifteen serovar were isolated, most frequently S. enteritidis (29.4%), but S.
      typhimurium only once (1.96%). The highest amount of salmonellae germs was found
      with 105 g in faeces from conveyor belts. There are no objections to the direct
      utilization of faeces as fertilizers from an epidemiological point of view. For
      epidemiological reasons, ventilated faeces from conveyor belts should not be
      directly sprayed over the soil. After air-drying in henhouses, these faeces
      should be stored and composted before they are used in agriculture. It was not
      possible to cultivate salmonellae and E. coli in summer and winter after the
      composting of dried hens' faeces. The salmonellae were no longer detectable from
      the 4th day onwards, native salmonellae from the 7th day (summer) and the 25th
      day (winter) onwards, and E. coli from the 88th day onwards. If all parameters,
      particularly the grain size, are observed, an epidemiologically perfect product
      comes into being after the fast drying of faeces.

PMID- 9190780
TI  - [Detection methods for Salmonella abortus ovis and examinations in sheep flocks
      in northern Baden-Wurttemberg].
AB  - Investigations into the incidence of Salmonella abortus ovis (S. abortus ovis)
      infections should not be neglected in diagnosis of ovine abortion cases. For
      detection of this pathogen agent, direct cultivation, as well as pre-enrichment
      combined with enrichment procedures in tetrathionate or Rappaport-Vassiliadis
      medium, should be performed with respect to the features of S. abortus ovis. The
      detection limit of S. abortus ovis using pre-enrichment and enrichment media
      could be determined using 6.5 x 10(3)-6.5 x 10(4) bacteria. For subsequent
      cultivation of S. abortus ovis Gassner, XLD or Rambach agar are suitable. In
      infected sheep showing no excretion of S. abortus ovis, the pathogen can be
      detected by serological studies using microagglutination or the ELISA test. The
      ELISA test proved to be more sensitive than the microagglutination test,
      detecting antibodies against S. abortus ovis in 17% of the 814 sheep tested. The
      microagglutination test revealed positive results in only 2% of the sheep tested.

PMID- 9190781
TI  - Clinical interpretation of "The efficacy of an early prevention program
      facilitated by occupational therapists: a follow-up study".

PMID- 9190782
TI  - [Changes in pesticide residues during various stages of preserved food
      production].

PMID- 9190783
TI  - [Fluorine and sciences].

PMID- 9190784
TI  - Infection control: past, present, and future.

PMID- 9190785
TI  - Network organization of cell metabolism: monosaccharide interconversion.
AB  - The structural properties of carbohydrate metabolism are being studied. The
      present contribution focuses mainly on those processes involving the transfer of
      carbon fragments among sugars. It is shown how enzymatic activities fix the way
      the system self-organizes stoichiometrically at the steady state. It is proven
      that there exists a specific correspondence between the set of all possible
      enzymic activities, the activity set, and the set of stoichiometrically
      compatible flux distributions through the pathway. On the one hand, there are
      enzymic activities that do not allow a stoichiometrically feasible coupling at
      the steady state of the reactions involved in the conversion. On the other hand,
      there are enzymic activities that are related to one or more flux distributions
      at the steady state (i.e. with one or several rate vectors respectively). For
      this latter group, it can be demonstrated that the structure of the system
      depends on other non-structural factors, such as boundary constraints and the
      kinetic parameters. As a consequence, it is suggested that this kind of metabolic
      process must be viewed as a complex reaction network instead of a sequential
      number of steps. Some implications of these derivations are illustrated for the
      particular conversion of CO2 --> C3. General remarks are also discussed within
      the framework of network models of cell metabolism.

PMID- 9190786
TI  - [Isolation and partial structural characteristics of major toxic components of
      Latrodectus pallidus venom].
AB  - Toxic components of the Latrodectus pallidus spider venom were isolated and
      characterized. The venom was shown to contain a toxin specific for mammals and at
      least one insectospecific toxin. Partial amino acid sequences of both toxins were
      determined, and their high structural homology with previously studied alpha
      latrotoxin and alpha-latroinsectotoxin from L. mactans tredecimguttatus was
      found.

PMID- 9190787
TI  - [Lysine residue as an amino acid substitute for conformational constraint of Xaa
      Asp fragment of biologically active peptides using side chain lactamization].
AB  - The model cyclopeptide Ac-Lys-Asp-NHMe was used to test Lys as a possible
      substitute for Xaa in peptide fragment Xaa-Asp whose conformational mobility
      would be constrained by lactamization of the Lys and Asp side chains. By means of
      theoretical conformational analysis, such a lactam was shown to be capable of
      fixing several conformations of the peptide. Among them, 32 conformations
      corresponded to 8 low-energy regions of the linear peptide Ac-Ala-Asp-NHMe, which
      was chosen as a model for the peptide fragment Xaa-Asp. In this case, the
      conformational possibilities of the Xaa residue were constrained to two regions
      of the Phi, Psi-map, (A + G) and C according to Zimmermann-Sheraga notation.

PMID- 9190789
TI  - [Cloning and expression of cDNA for tobacco rab1, and structural-functional
      analysis of the protein].
AB  - rab1 cDNA coding for a small GTP binding protein Rab1 was isolated from cDNA
      library of tobacco (Nicotiana tabacum) leaves. The primary structure of this
      protein was deduced from the rab1 structure. Tobacco rab1 cDNA was expressed in
      Escherichia coli, and the product was purified and shown to exhibit GTPase
      activity. A set of Rab1 mutants with altered GTP binding and/or GTPase activities
      was obtained. Polyclonal antipeptide antibodies were raised against a sequence in
      the C-terminal region of the tobacco Rab1 capable of recognizing this protein.

PMID- 9190788
TI  - [Activity of alpha-chymotrypsin immobilized in nanocapsules of poly(N,N-didodecyl
      N,N-diallylammonium bromide)].
AB  - Biocatalytic nanocapsule systems containing alpha-chymotrypsin in the inner
      aqueous cavity were synthesized. These systems can function in both organic
      solvents and aqueous media. To this end, the reversed hydrated micelles of N,N
      diallyl-N,N-didodecylammonium bromide (DDAB) in cyclohexane (w0 = 22) with alpha
      chymotrypsin encapsulated were subjected to UV-induced polymerization. After
      precipitation with acetone, the nanocapsules were transferred into water with the
      use of AOT and subsequent sonication. The unilamellar liposomes thus formed have
      an inner monolayer from the polyDDAB network, an outer monolayer from the AOT
      molecules, and contain alpha-chymotrypsin in the inner aqueous medium. According
      to the light scattering data, the mean outer diameter of the nanocapsules is 20
      nm. When compared with free enzyme in respect to p-nitrophenyl acetate
      hydrolysis, the alpha-chymotrypsin encapsulated in the liposomes exhibits the
      same K(m) value, but its values of kcat and of the inhibition constant by the
      reaction product Kp decreased by factors of 1.2 and 1.6, respectively. The alpha
      chymotrypsin immobilized in the nanocapsules is thermally stable and
      catalytically active up to 80 degrees C. The polymer network hinders
      conformational rearrangements of the enzyme molecule upon heating.

PMID- 9190790
TI  - [Sensitized photomodification by binary systems. I. Synthesis of oligonucleotide
      reagents, and the effect of their structure on the efficacy of target
      modification].
AB  - A highly effective sensitized photomodification of the target DNA by a binary
      system of oligonucleotide reagents complementary to adjacent regions of the
      target was accomplished. One of the oligonucleotides carries a photoregent p
      azidotetrafluorobenzamide, and the other carries a pyrene sensitizer. Synthesis
      of the oligonucleotide derivatives was described. The rate and efficacy of the
      direct and sensitized target photomodifications depending on the location of the
      photoreagent and sensitizer at the 3'- and 5'-terminal phosphates and on the
      length of the linker between the sensitizer and addressed nucleotide were
      studied. The oligonucleotide derivatives with the photoreagent at the 3' terminus
      proved to be more effective (yield of the covalent adducts 70%). The rate of
      photomodification sensitized by UV light (365-390 nm) is 100-1500-fold higher
      than that of the direct site-specific modification and decreases with an
      increasing length of the linker. In all cases, modification occurs at the
      guanosine residue located near the photoreagent.

PMID- 9190791
TI  - [Regulation of translation of the distal lacZ gene in polycistronic mRNA by the
      ribosome stream from the proximal gene].
AB  - Four series of plasmids (pNSI, pNSII, pNLI, and pNLII) with artificial
      polycistrons containing the lacZ test gene were constructed. These plasmids coded
      for polycistronic mRNAs with two different types of cistron (orfZ and lacZ)
      coupling: in pNSI and pNLI, the orfZ termination codon and the lacZ initiation
      codon overlapped (type I); in pNSII and pNLII, the orfZ termination codon, was
      located upstream of the lacZ SD sequence. The length of the orfZ cistron was 60
      bp in pNSI and pNSII or 300 bp in pNLI and pNLII. Plasmids with the same type of
      cistron coupling contained the same lacZ translation initiation region, whereas
      the structure of the orfZ translation initiation region varied, thereby providing
      varying efficiency of the orfZ gene translation. The effect of these variations
      on the efficiency of the lacZ gene translation was evaluated by direct
      measurement of the beta-galactosidase activity in Escherichia coli cells
      transformed with the corresponding plasmids. We found that the level of
      translation of the distal lacZ gene depended on the ribosome stream from the
      proximal gene and was maximal at the optimal ribosome stream level, which, in
      turn, depended on the type of cistron coupling.

PMID- 9190792
TI  - [New allele-specific primers for detection of Leiden mutation in exon 10 of
      factor V gene in thrombophilias].
AB  - New allele-specific primers were developed which enable the facile and effective
      identification of the Leiden mutation in the human genome using PCR. One of the
      primers (allele-nonspecific), which is complementary to the nucleotide sequence
      of the intron 10 sense strand, [(5')TCTCTTGAAGGAAATGCCCCATTA], was described by
      B. Dahlback in 1994. Two other primers (allele-specific),
      (5')TAAGAGCAGATCCCTGGACAGCCA and (5')TAAGAGCAGATCCCTGGACACGCA), contained a 3'
      terminal nucleotide corresponding to the nucleotide of the mutant allele, as well
      as a nucleotide noncomplementary to the template DNA near the 3'-end (shown by
      boldface type). When used in combination with allele-nonspecific primers, both
      allele-specific primers were equally effective in detecting the Leiden mutation
      in the human factor V gene. Using these primers, two Leiden mutations in the
      heterozygous state were found in 20 patients with deep vein thromboses and
      pulmonary thromboembolia.

PMID- 9190793
TI  - [Artificially functionalized polyenoic fatty acids--a new lipid bioregulators].
AB  - Dopamine, histamine, serotonin, and serotonin analogs were acylated with
      arachidonic and eicosapentaenoic acids, and the reaction products were named as
      artificially functionalized fatty acids (AFFA). The amides of arachidonic acid
      with serotonin, dopamine, and histamine were found to inhibit human platelet
      aggregation induced by ADP, arachidonic acid and adrenaline. Amides of
      arachidonic and eicosapentaeonic acids with serotonin and dopamine protect sea
      urchin early embryos against cytotoxic action of serotonin and histamine
      antagonists. These effects are not connected with the possible hydrolytic
      cleavage of AFFA to their constituent polyenoic fatty acids and amines.
      Arachidonic acid dopaminamide was shown to be a substrate of soybean 15
      lipoxygenase, whereas the arachidonic acid amides with serotonin and its
      derivatives were resistant to this enzyme. Moreover, arachidonic acid
      serotoninamide turned out to be an irreversible lipoxygenase inhibitor.
      Considerable amount of hydroxyl radicals (fluorescent assay) were found for the
      first time to accompany lipoxygenase oxidation of linoleic acid; arachidonic acid
      serotoninamide blocked this process completely. Therefore, it was concluded that
      AFFA possess specific biological activity and can be considered as a novel group
      of lipid bioregulators.

PMID- 9190794
TI  - [The first member of a novel family of eukaryotic transcription factors detected
      by the heterospecific complementation].
AB  - The cDNA of a previously uncharacterized gene fet5 (factor of eukaryotic
      transcription, clone no. 5) of the fission yeast Schizosaccharomyces pombe was
      cloned by the heterospecific complementation of a conditional mutant of
      Saccharomyces cerevisiae defective in the function of the RNA polymerases I-III
      common subunit ABC10 beta. The gene encodes a new factor of eukaryotic
      transcription, Fet5, the first member of a superfamily of proteins for which the
      area of functioning is determined. The Fet5-superfamily consists of three
      distinct families of proteins highly evolutionarily conserved and widely spread
      among eukaryotes. Features of the Fet5 amino acid sequence suggest that it
      belongs to ATP/GTP-binding proteins.

PMID- 9190795
TI  - Interactions of the RepA1 protein with its replicon targets: two opposing roles
      in control of plasmid replication.
AB  - By studying the interaction of derivatives of RepFIC miniplasmids, we were able
      to demonstrate that under certain conditions the RepA1 initiator protein inhibits
      plasmid replication. An analysis of cloned derivatives whose replication is
      inhibited by the RepA1 protein revealed the existence of two areas of the RepFIC
      genome that interact with RepA1 in the inhibition reaction. One of these areas,
      which occurs in the origin region, was explored by in vivo methylation protection
      footprinting studies. The protected area was 200 bp long and showed a definite
      periodicity of protected and hypersensitive sites, suggesting that RepA1 promotes
      a topological change in the RepFIC genome. The significance of our results is
      discussed in the context of plasmid replication control.

PMID- 9190796
TI  - The rnhB gene encoding RNase HII of Streptococcus pneumoniae and evidence of
      conserved motifs in eucaryotic genes.
AB  - A single RNase H enzyme was detected in extracts of Streptococcus pneumoniae. The
      gene encoding this enzyme was cloned and expressed in Escherichia coli, as
      demonstrated by its ability to complement a double-mutant rnhA recC strain.
      Sequence analysis of the cloned DNA revealed an open reading frame of 290 codons
      that encodes a polypeptide of 31.9 kDa. The predicted protein exhibits a low
      level of homology (19% identity of amino acid residues) to RNase HII encoded by
      rnhB of E. coli. Identification of the S. pneumoniae RNase HII translation start
      site by amino-terminal sequencing of the protein and of mRNA start sites by
      primer extension with reverse transcriptase showed that the major transcript
      encoding rnhB begins at the protein start site. Comparison of the S. pneumoniae
      and E. coli RNase HII sequences and sequences of other, putative bacterial rnhB
      gene products surmised from sequencing data revealed three conserved motifs. Use
      of these motifs to search for homologous genes in eucaryotes demonstrated the
      presence of rnhB genes in a yeast and a roundworm. Partial rnhB gene sequences
      were detected among expressed sequences of mouse and human cells. From these
      data, it appears that RNase HII is universally present in living cells.

PMID- 9190797
TI  - The WH11 gene of Candida albicans is regulated in two distinct developmental
      programs through the same transcription activation sequences.
AB  - Candida albicans strain WO-1 undergoes two developmental programs, the bud-hypha
      transition and high-frequency phenotypic switching in the form of the white
      opaque transition. The WH11 gene is expressed in the white budding phase but is
      inactive in the white hyphal phase and in the opaque budding phase. WH11
      expression, therefore, is regulated in the two developmental programs. Through
      fusions between deletion derivatives of the WH11 promoter and the newly developed
      Renilla reniformis luciferase, the WH11 promoter has been characterized in the
      two developmental programs. Three transcription activation sequences, two strong
      and one weak, are necessary for the full expression of WH11 in the white budding
      phase, but no negative regulatory sequences were revealed as playing a role in
      either the white hyphal phase or the opaque budding phase. These results suggest
      that regulation is solely through activation in the white budding phase and the
      same mechanism, therefore, is involved in regulating the differential expression
      of WH11 in the alternative white and opaque phases of switching and the budding
      and hyphal phases of dimorphism.

PMID- 9190798
TI  - Size of cotA and identification of the gene product in Synechocystis sp. strain
      PCC6803.
AB  - cotA of Synechocystis sp. strain PCC6803 is a gene involved in light-induced
      proton extrusion (A. Katoh, M. Sonoda, H. Katoh, and T. Ogawa, J. Bacteriol.
      178:5452-5455, 1996). There are two possible initiation codons in cotA, and
      either long (L-) or short (S-) cotA encoding a protein of 440 or 247 amino acids
      could be postulated. To determine the gene size, we inserted L-cotA and S-cotA
      into the genome of a cotA-less mutant (M29) to construct M29(L-cotA) and M29(S
      cotA), respectively. M29(L-cotA) showed essentially the same net proton movement
      profile as the wild type, whereas no light-induced proton extrusion was observed
      with M29(S-cotA). Two kinds of antibodies were raised against partial gene
      products of the N- and C-terminal regions of L-cotA, respectively, fused to
      glutathione S-transferase expressed in Escherichia coli. Both antibodies cross
      reacted with a band at 52 kDa in both cytoplasmic and thylakoid membrane
      fractions of the wild-type cells. The same cross-reacting band was present in the
      membranes of M29(L-cotA) but not in M29 or M29(S-cotA). These antibodies cross
      reacted more strongly with the cytoplasmic membrane fraction than with the
      thylakoid membrane fraction. The antibody against NrtA, a nitrate transporter
      protein present only in the cytoplasmic membrane, also cross-reacted with the
      thylakoid membrane fraction strongly. Based on these results we concluded that
      CotA of 440 amino acids (51 kDa) is located in the cytoplasmic membrane. Whether
      CotA is absent in the thylakoid membrane remains to be solved.

PMID- 9190800
TI  - Oxidation of aliphatic olefins by toluene dioxygenase: enzyme rates and product
      identification.
AB  - Toluene dioxygenase from Pseudomonas putida F1 has been studied extensively with
      aromatic substrates. The present work examined the toluene dioxygenase-catalyzed
      oxidation of various halogenated ethenes, propenes, butenes and nonhalogenated
      cis-2-pentene, an isomeric mix of 2-hexenes, cis-2-heptene, and cis-2-octene as
      substrates for toluene dioxygenase. Enzyme specific activities were determined
      for the more water-soluble C2 to C5 compounds and ranged from <4 to 52 nmol per
      min per mg of protein. Trichloroethene was oxidized at a rate of 33 nmol per min
      per mg of protein. Products from enzyme reactions were identified by gas
      chromatography-mass spectrometry. Proton and carbon nuclear magnetic resonance
      spectroscopy of compounds from whole-cell incubation confirmed the identity of
      products. Substrates lacking a halogen substituent on sp2 carbon atoms were
      dioxygenated, while those with halogen and one or more unsubstituted allylic
      methyl groups were monooxygenated to yield allylic alcohols. 2,3-Dichloro-1
      propene, containing both a halogenated double bond and a halogenated allylic
      methyl group, underwent monooxygenation with allylic rearrangement to yield an
      isomeric mixture of cis- and trans-2,3-dichloro-2-propene-1-ol.

PMID- 9190799
TI  - Role of the nhaC-encoded Na+/H+ antiporter of alkaliphilic Bacillus firmus OF4.
AB  - Application of protoplast transformation and single- and double-crossover
      mutagenesis protocols to alkaliphilic Bacillus firmus OF4811M (an auxotrophic
      strain of B. firmus OF4) facilitated the extension of the sequence of the
      previously cloned nhaC gene, which encodes an Na+/H+ antiporter, and the
      surrounding region. The nhaC gene is part of a likely 2-gene operon encompassing
      nhaC and a small gene that was designated nhaS; the operon is preceded by novel
      direct repeats. The predicted alkaliphile NhaC, based on the extended sequence
      analysis, would be a membrane protein with 462 amino acid residues and 12
      transmembrane segments that is highly homologous to the deduced products of
      homologous genes of unknown function from Bacillus subtilis and Haemophilus
      influenzae. The full-length version of nhaC complemented the Na+-sensitive
      phenotype of an antiporter-deficient mutant strain of Escherichia coli but not
      the alkali-sensitive growth phenotypes of Na+/H+-deficient mutants of either
      alkaliphilic B. firmus OF4811M or B. subtilis. Indeed, NhaC has no required role
      in alkaliphily, inasmuch as the nhaC deletion strain of B. firmus OF4811M, N13,
      grew well at pH 10.5 at Na+ concentrations equal to or greater than 10 mM. Even
      at lower Na+ concentrations, N13 exhibited only a modest growth defect at pH
      10.5. This was accompanied by a reduced capacity to acidify the cytoplasm
      relative to the medium compared to the wild-type strain or to N13 complemented by
      cloned nhaC. The most notable deficiency observed in N13 was its poor growth at
      pH 7.5 and Na+ concentrations up to 25 mM. During growth at pH 7.5, NhaC is
      apparently a major component of the relatively high affinity Na+/H+ antiport
      activity available to extrude the Na+ and to confer some initial protection in
      the face of a sudden upshift in external pH, i.e., before full induction of
      additional antiporters. Consistent with the inference that NhaC is a relatively
      high affinity, electrogenic Na+/H+ antiporter, N13 exhibited a defect in
      diffusion potential-energized efflux of 22Na+ from right-side-out membrane
      vesicles from cells that were preloaded with 2 mM Na+ and energized at pH 7.5.
      When the experiment was conducted with vesicles loaded with 25 mM Na+, comparable
      efflux was observed in preparations from all the strains.

PMID- 9190801
TI  - Altered localization of HrpZ in Pseudomonas syringae pv. syringae hrp mutants
      suggests that different components of the type III secretion pathway control
      protein translocation across the inner and outer membranes of gram-negative
      bacteria.
AB  - Pseudomonas syringae pv. syringae 61 (Pss61) secretes the HrpZ harpin by a type
      III protein secretion pathway encoded by a cluster of hrp (hypersensitive
      response and pathogenicity) and hrc genes. The nine hrc genes represent a subset
      of hrp genes that are also conserved in the type III virulence protein secretion
      systems of animal pathogenic Yersinia, Shigella, and Salmonella spp. The hrpJ and
      hrpU operons contain seven hrc genes (counting hrcQ(A) and hrcQ(B) as one gene),
      all with additional homologs involved in flagellar biogenesis and secretion, and
      five of which encode predicted inner membrane proteins. The hrpC and hrpZ operons
      encode HrcC and HrcJ, respectively, which are associated with the outer membrane.
      Interposon mutants affected in all of the hrc genes in the hrpJ and hrpU operons
      and TnphoA-induced hrcC and hrcJ mutants were assayed for altered localization of
      HrpZ in mid-log-phase cultures by immunoblotting sodium dodecyl sulfate
      polyacrylamide gels that were run with various cell fractions. The hrpJ and hrpU
      operon mutants revealed a novel phenotype of partially reduced accumulation of
      HrpZ in the total culture (despite wild-type levels of hrpZ operon
      transcription), all of which was cell bound and equivalent in level to that of
      cell-bound HrpZ in the wild type. The hrcC and hrcJ mutant cultures accumulated
      the same total amount of HrpZ as the wild type, but the HrpZ was cell bound.
      Among all the strains tested, only the hrcC mutant accumulated significant
      amounts of HrpZ in the periplasm, as indicated by selective release through
      spheroplasting. Analysis of nonpolar mutations in the hrpU and hrpC operons
      support the results obtained with polar mutations. These observations indicate
      that a constant pool of HrpZ is maintained in the cytoplasm of Pss61 despite
      secretion deficiencies, that the hrpJ and hrpU operons encode an alternative to
      the Sec (general protein export) pathway for translocation across the inner
      membrane, that genes in the hrpC operon are necessary for translocation across
      the outer membrane, and that the Pss61 Hrp system permits study of two
      genetically distinguishable stages in type III protein secretion.

PMID- 9190802
TI  - AUT3, a serine/threonine kinase gene, is essential for autophagocytosis in
      Saccharomyces cerevisiae.
AB  - Autophagocytosis is a starvation-induced process, carrying proteins destined for
      degradation to the lysosome. In the yeast Saccharomyces cerevisiae, the
      autophagic process is visualized by the appearance of autophagic vesicles in the
      vacuoles of proteinase yscB-deficient strains during starvation. aut3-1 mutant
      cells which exhibit a block in the autophagic process have been isolated
      previously. By using the drastically reduced sporulation frequency of homozygous
      aut3-1 diploid cells, the AUT3 gene was cloned by complementation. The Aut3
      protein consists of 897 amino acids. The amino-terminal part of the protein shows
      significant homologies to serine/threonine kinases. aut3 null mutant cells are
      fully viable on rich media but show a reduced survival rate upon starvation. They
      are unable to accumulate autophagic vesicles in the vacuole during starvation.
      Starvation-induced vacuolar protein breakdown is almost completely impaired in
      aut3-deficient cells. Vacuolar morphology and acidification are not influenced in
      aut3-deficient cells. Also, secretion of invertase, endocytic uptake of Lucifer
      Yellow, and vacuolar protein sorting appear wild type like in aut3-deficient
      cells, suggesting autophagocytosis as a novel route for the transport of proteins
      from the cytosol to the vacuole. By using a fusion of Aut3p with green
      fluorescent protein, Aut3p was localized to the cytosol.

PMID- 9190803
TI  - In vivo and in vitro effects of thiolactomycin on fatty acid biosynthesis in
      Streptomyces collinus.
AB  - A stable-isotope assay was used to analyze the effectiveness of various
      perdeuterated short-chain acyl coenzyme A (acyl-CoA) compounds as starter units
      for straight- and branched-chain fatty acid biosynthesis in cell extracts of
      Streptomyces collinus. In these extracts perdeuterated isobutyryl-CoA was
      converted to isopalmitate (a branched-chain fatty acid), while butyryl-CoA was
      converted to palmitate (a straight-chain fatty acid). These observations are
      consistent with previous in vivo analyses of fatty acid biosynthesis in S.
      collinus, which suggested that butyryl-CoA and isobutyryl-CoA function as starter
      units for palmitate and isopalmitate biosynthesis, respectively. Additionally, in
      vitro analysis demonstrated that acetyl-CoA can function as a starter unit for
      palmitate biosynthesis. Palmitate biosynthesis and isopalmitate biosynthesis in
      these cell extracts were both effectively inhibited by thiolactomycin, a known
      type II fatty acid synthase inhibitor. In vivo experiments demonstrated that
      concentrations of thiolactomycin ranging from 0.1 to 0.2 mg/ml produced both a
      dramatic decrease in the cellular levels of branched-chain fatty acids and a
      surprising three- to fivefold increase in the cellular levels of the straight
      chain fatty acids palmitate and myristate. Additional in vivo incorporation
      studies with perdeuterated butyrate suggested that, in accord with the in vitro
      studies, the biosynthesis of the palmitate from butyryl-CoA decreases in the
      presence of thiolactomycin. In contrast, in vivo incorporation studies with
      perdeuterated acetate demonstrated that the biosynthesis of palmitate from acetyl
      CoA increases in the presence of thiolactomycin. These observations clearly
      demonstrate that isobutyryl-CoA is a starter unit for isopalmitate biosynthesis
      and that either acetyl-CoA or butyryl-CoA can be a starter unit for palmitate
      biosynthesis in S. collinus. However, the pathway for palmitate biosynthesis from
      acetyl-CoA is less sensitive to thiolactomycin, and it is suggested that the
      basis for this difference is in the initiation step.

PMID- 9190804
TI  - Evidence that the N-terminal part of the S-layer protein from Bacillus
      stearothermophilus PV72/p2 recognizes a secondary cell wall polymer.
AB  - The S-layer of Bacillus stearothermophilus PV72/p2 shows oblique lattice symmetry
      and is composed of identical protein subunits with a molecular weight of 97,000.
      The isolated S-layer subunits could bind and recrystallize into the oblique
      lattice on native peptidoglycan-containing sacculi which consist of peptidoglycan
      of the A1gamma chemotype and a secondary cell wall polymer with an estimated
      molecular weight of 24,000. The secondary cell wall polymer could be completely
      extracted from peptidoglycan-containing sacculi with 48% HF, indicating the
      presence of phosphodiester linkages between the polymer chains and the
      peptidoglycan backbone. The cell wall polymer was composed mainly of GlcNAc and
      ManNAc in a molar ratio of 4:1, constituted about 20% of the peptidoglycan
      containing sacculus dry weight, and was also detected in the fraction of the S
      layer self-assembly products. Extraction experiments and recrystallization of the
      whole S-layer protein and proteolytic cleavage fragments confirmed that the
      secondary cell wall polymer is responsible for anchoring the S-layer subunits by
      the N-terminal part to the peptidoglycan-containing sacculi. In addition to this
      binding function, the cell wall polymer was found to influence the in vitro self
      assembly of the guanidinium hydrochloride-extracted S-layer protein. Chemical
      modification studies further showed that the secondary cell wall polymer does not
      contribute significant free amino or carboxylate groups to the peptidoglycan
      containing sacculi.

PMID- 9190805
TI  - Compositional biases of bacterial genomes and evolutionary implications.
AB  - We compare and contrast genome-wide compositional biases and distributions of
      short oligonucleotides across 15 diverse prokaryotes that have substantial
      genomic sequence collections. These include seven complete genomes (Escherichia
      coli, Haemophilus influenzae, Mycoplasma genitalium, Mycoplasma pneumoniae,
      Synechocystis sp. strain PCC6803, Methanococcus jannaschii, and Pyrobaculum
      aerophilum). A key observation concerns the constancy of the dinucleotide
      relative abundance profiles over multiple 50-kb disjoint contigs within the same
      genome. (The profile is rhoXY* = fXY*/fX*fY* for all XY, where fX* denotes the
      frequency of the nucleotide X and fY* denotes the frequency of the dinucleotide
      XY, both computed from the sequence concatenated with its inverted complementary
      sequence.) On the basis of this constancy, we refer to the collection [rhoXY*] as
      the genome signature. We establish that the differences between [rhoXY*] vectors
      of 50-kb sample contigs of different genomes virtually always exceed the
      differences between those of the same genomes. Various di- and tetranucleotide
      biases are identified. In particular, we find that the dinucleotide CpG=CG is
      underrepresented in many thermophiles (e.g., M. jannaschii, Sulfolobus sp., and
      M. thermoautotrophicum) but overrepresented in halobacteria. TA is broadly
      underrepresented in prokaryotes and eukaryotes, but normal counts appear in
      Sulfolobus and P. aerophilum sequences. More than for any other bacterial genome,
      palindromic tetranucleotides are underrepresented in H. influenzae. The M.
      jannaschii sequence is unprecedented in its extreme underrepresentation of CTAG
      tetranucleotides and in the anomalous distribution of CTAG sites around the
      genome. Comparative analysis of numbers of long tetranucleotide microsatellites
      distinguishes H. influenzae. Dinucleotide relative abundance differences between
      bacterial sequences are compared. For example, in these assessments of
      differences, the cyanobacteria Synechocystis, Synechococcus, and Anabaena do not
      form a coherent group and are as far from each other as general gram-negative
      sequences are from general gram-positive sequences. The difference of M.
      jannaschii from low-G+C gram-positive proteobacteria is one-half of the
      difference from gram-negative proteobacteria. Interpretations and hypotheses
      center on the role of the genome signature in highlighting similarities and
      dissimilarities across different classes of prokaryotic species, possible
      mechanisms underlying the genome signature, the form and level of genome
      compositional flux, the use of the genome signature as a chronometer of molecular
      phylogeny, and implications with respect to the three putative eubacterial,
      archaeal, and eukaryote domains of life and to the origin and early evolution of
      eukaryotes.

PMID- 9190806
TI  - New classes of mutants in complementary chromatic adaptation provide evidence for
      a novel four-step phosphorelay system.
AB  - Complementary chromatic adaptation appears to be controlled by a complex
      regulatory system with similarity to four-step phosphorelays. Such pathways
      utilize two histidine and two aspartate residues for signal transduction.
      Previous studies of the signaling system controlling complementary chromatic
      adaptation have uncovered two elements of this pathway, a putative sensor, RcaE,
      and a response regulator, RcaC. In this work, we describe a second response
      regulator controlling complementary chromatic adaptation, RcaF, and identify
      putative DNA binding and histidine phosphoacceptor domains within RcaC. RcaF is a
      small response regulator with similarity to SpoOF of Bacillus subtilis; the
      latter functions in the four-step phosphorelay system controlling sporulation. We
      have also determined that within this phosphorelay pathway, RcaE precedes RcaF,
      and RcaC is probably downstream of RcaE and RcaF. This signal transduction
      pathway is novel because it appears to use at least five, instead of four,
      phosphoacceptor domains in the phosphorelay circuit.

PMID- 9190807
TI  - Contribution of partner switching and SpoIIAA cycling to regulation of sigmaF
      activity in sporulating Bacillus subtilis.
AB  - sigmaF, the first compartment-specific transcription factor in sporulating
      Bacillus subtilis, is negatively regulated by an anti-sigma factor, SpoIIAB.
      SpoIIAB has an alternative binding partner, SpoIIAA. To see whether (as has been
      proposed) SpoIIAB's binding preference for SpoIIAA or sigmaF depends on the
      nature of the adenine nucleotide present, we used surface plasmon resonance to
      measure the dissociation constants of the three complexes SpoIIAA-SpoIIAB-ADP,
      sigmaF-SpoIIAB-ADP, and sigmaF-SpoIIAB-ATP. The results suggested that SpoIIAB's
      choice of binding partner is unlikely to depend on the ATP/ADP ratio in the cell.
      The intracellular concentrations of sigmaF, SpoIIAB, SpoIIAA, and SpoIIAA
      phosphate (SpoIIAA-P) were measured by quantitative immunoblotting between 0 and
      3 h after the beginning of sporulation (t0 to t3). sigmaF and SpoIIAB were barely
      detectable at t0, but their concentrations increased in parallel to reach maxima
      at about t1.5. SpoIIAA-P increased steadily to a maximum at t3, but
      nonphosphorylated SpoIIAA was detectable only from t1.5, reached a maximum at
      t2.5, and then declined. Kinetic studies of the phosphorylation of SpoIIAA
      catalyzed by SpoIIAB suggested that the reaction was limited by a very slow
      release of one of the products (SpoIIAA-P or ADP) from SpoIIAB, with a turnover
      of about once per 20 min. This remarkable kinetic property provides an unexpected
      mechanism for the regulation of sigmaF. We propose that when SpoIIE (which
      dephosphorylates SpoIIAA-P) is active at the same time as SpoIIAB, SpoIIAA cycles
      repeatedly between the phosphorylated and nonphosphorylated forms. This cycling
      sequesters SpoIIAB in a long-lived complex and prevents it from inhibiting
      sigmaF.

PMID- 9190808
TI  - Vfr controls quorum sensing in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa controls several genes in a cell density-dependent manner
      through a phenomenon termed quorum sensing. The transcriptional activator protein
      of the las quorum-sensing system is encoded for by the lasR gene, which is at the
      top of a quorum-sensing hierarchy. The activation of LasR as a transcriptional
      activator induces the expression of multiple genes that code for factors
      important for virulence, and rhlR, which encodes the transcriptional activator
      protein of the P. aeruginosa rhl quorum-sensing system. Elucidating the method of
      lasR regulation is crucial to understanding P. aeruginosa quorum sensing. In this
      report, we present studies on the transcriptional control of lasR. We identified
      two distinct transcriptional start sites for lasR that were located 201 bp
      (transcript T1) and 231 bp (transcript T2) upstream from the lasR start of
      translation. With the use of transcriptional lasRp-lacZ fusions, we showed that
      in P. aeruginosa, lasR expression is cell density dependent. This gene was
      expressed at a basal level until it was induced during the second half of log
      phase growth, with expression becoming maximal during stationary-phase growth. We
      also showed that lasR expression was regulated through the cyclic AMP receptor
      protein (CRP)-binding consensus sequence in its promoter region. Our results from
      P. aeruginosa mutant studies and gel retardation assays indicated that this
      regulation was mediated by Vfr, a homolog of the Escherichia coli CRP.

PMID- 9190809
TI  - Functional analyses of a variety of chimeric dioxygenases constructed from two
      biphenyl dioxygenases that are similar structurally but different functionally.
AB  - The biphenyl dioxygenases (BP Dox) of strains Pseudomonas pseudoalcaligenes KF707
      and Pseudomonas cepacia LB400 exhibit a distinct difference in substrate ranges
      of polychlorinated biphenyls (PCB) despite nearly identical amino acid sequences.
      The range of congeners oxidized by LB400 BP Dox is much wider than that oxidized
      by KF707 BP Dox. The PCB degradation abilities of these BP Dox were highly
      dependent on the recognition of the chlorinated rings and the sites of oxygen
      activation. The KF707 BP Dox recognized primarily the 4'-chlorinated ring (97%)
      of 2,5,4'-trichlorobiphenyl and introduced molecular oxygen at the 2',3'
      position. The LB400 BP Dox recognized primarily the 2,5-dichlorinated ring (95%)
      of the same compound and introduced O2 at the 3,4 position. It was confirmed that
      the BphA1 subunit (iron-sulfur protein of terminal dioxygenase encoded by bphA1)
      plays a crucial role in determining the substrate selectivity. We constructed a
      variety of chimeric bphA1 genes by exchanging four common restriction fragments
      between the KF707 bphA1 and the LB400 bphA1. Observation of Escherichia coli
      cells expressing various chimeric BP Dox revealed that a relatively small number
      of amino acids in the carboxy-terminal half (among 20 different amino acids in
      total) are involved in the recognition of the chlorinated ring and the sites of
      dioxygenation and thereby are responsible for the degradation of PCB. The site
      directed mutagenesis of Thr-376 (KF707) to Asn-376 (LB400) in KF707 BP Dox
      resulted in the expansion of the range of biodegradable PCB congeners.

PMID- 9190810
TI  - Isolation and analysis of the Xanthomonas alkyl hydroperoxide reductase gene and
      the peroxide sensor regulator genes ahpC and ahpF-oxyR-orfX.
AB  - From Xanthomonas campestris pv. phaseoli, we have isolated by two independent
      methods genes involved in peroxide detoxification (ahpC and ahpF), a gene
      involved in peroxide sensing and transcription regulation (oxyR), and a gene of
      unknown function (orfX). Amino acid sequence analysis of AhpC, AhpF, and OxyR
      showed high identity with bacterial homologs. OrfX was a small cysteine-rich
      protein with no significant homology to known proteins. The genes ahpC, ahpF,
      oxyR, and orfX were arranged in a head-to-tail fashion. This unique arrangement
      was conserved in all of the Xanthomonas strains tested. The functionalities of
      both the ahpC and oxyR genes were demonstrated. In X. campestris pv. phaseoli,
      increased expression of ahpC alone conferred partial protection against growth
      retardation and killing by organic hydroperoxides but not by H2O2 or superoxide
      generators. These genes are likely to have important physiological roles in
      protection against peroxide toxicity in Xanthomonas.

PMID- 9190811
TI  - Characterization of transcription organization and analysis of unique expression
      patterns of an alkyl hydroperoxide reductase C gene (ahpC) and the peroxide
      regulator operon ahpF-oxyR-orfX from Xanthomonas campestris pv. phaseoli.
AB  - We have analyzed the transcription organization of ahpC, ahpF, oxyR, and orfX
      from Xanthomonas campestris pv. phaseoli. ahpC was transcribed as a monocistronic
      0.6-kb mRNA, while ahpF-oxyR-orfX were transcribed as a polycistronic
      approximately 3.0-kb-long mRNA. The novel transcription organization of these
      genes has not observed in other bacteria. Western analysis showed that oxidants
      (peroxides and superoxide anions), a thiol reagent (N-ethylmaleimide), and CdCl2
      caused large increases in the steady-state level of AhpC. Growth at alkaline pH
      also moderately induced AhpC accumulation. Thermal and osmotic stresses did not
      alter the levels of AhpC. Northern blotting results confirmed that oxidant- and
      CdCl2-induced AhpC accumulation was due to increased levels of ahpC transcripts.
      Analysis of oxyR expression revealed a unique pattern. Unlike other bacterial
      systems, peroxides and a superoxide generator induced accumulation of OxyR.
      Northern blotting results confirmed that these oxidants induced expression of
      oxyR operon. This novel regulatory pattern could be generally important. The
      transcription organization and patterns of chemicals and stress induction of ahpC
      and oxyR differed from those of other bacteria and are likely to be important for
      X. campestris pv. phaseoli survival during exposure to oxidants.

PMID- 9190812
TI  - Molecular characterization of the mde operon involved in L-methionine catabolism
      of Pseudomonas putida.
AB  - A 15-kb region of Pseudomonas putida chromosomal DNA containing the mde operon
      and an upstream regulatory gene (mdeR) has been cloned and sequenced. The mde
      operon contains two structural genes involved in L-methionine degradative
      metabolism: the already-identified mdeA, which encodes L-methionine gamma-lyase
      (H. Inoue, K. Inagaki, M. Sugimoto, N. Esaki, K. Soda, and H. Tanaka. J. Biochem.
      (Tokyo) 117:1120-1125, 1995), and mdeB, which encodes a homologous protein to the
      homodimeric-type E1 component of pyruvate dehydrogenase complex. A rho
      independent terminator was present just downstream of mdeB, and open reading
      frames corresponding to other components of alpha-keto acid dehydrogenase complex
      were not found. When MdeB was overproduced in Escherichia coli, the cell extract
      showed the E1 activity with high specificity for alpha-ketobutyrate rather than
      pyruvate. These results suggest that MdeB plays an important role in the
      metabolism of alpha-ketobutyrate produced by MdeA from L-methionine. Accordingly,
      mdeB encodes a novel E1 component, alpha-ketobutyrate dehydrogenase E1 component,
      of an unknown alpha-keto acid dehydrogenase complex in P. putida. In addition, we
      found that the mdeR gene was located on the opposite strand and began at 127 bp
      from the translational start site of mdeA. The mdeR gene product has been
      identified as a member of the leucine-responsive regulatory protein (Lrp) family
      and revealed to act as an essential positive regulator allowing the expression of
      the mdeAB operon.

PMID- 9190813
TI  - sar Genetic determinants necessary for transcription of RNAII and RNAIII in the
      agr locus of Staphylococcus aureus.
AB  - The temporal expression of most virulence factors in Staphylococcus aureus is
      regulated by pleiotropic loci such as agr and sar. We have previously shown that
      the sar locus affects hemolysin production because it is required for agr
      transcription. To delineate the sar genetic determinant required for agr
      transcription, single copies of fragments from the sar locus, encompassing the
      individual sar transcripts (sarA, sarC, and sarB), were introduced into a sar
      mutant via the integration vector pCL84. Although a DNA fragment encompassing the
      sarA transcript plus a 189-bp upstream region was sufficient for agr expression,
      complementation analysis revealed that the sarB transcript was the most effective
      in augmenting agr transcription as determined by RNAII and RNAIII transcription
      and gel retardation assays with the P2 and P3 promoters of agr. As the region
      upstream of the sarA transcript encodes a 39-amino-acid open reading frame, ORF3,
      it is possible that posttranslational cooperation between the sarA gene product
      and ORF3 may be necessary for optimal agr expression. Deletion studies
      demonstrated that an intact sarA gene is essential for agr transcription.
      However, mutagenesis and in vitro translation studies revealed that unlike the
      agr locus, the required element is the SarA protein and not the RNA molecule.
      Taken together, these results indicate that the sarA-encoded protein, possibly in
      conjunction with peptides encoded in the upstream region, regulates hemolysin
      production by controlling agr P2 and P3 transcription.

PMID- 9190814
TI  - Pathways for utilization of carbon reserves in Desulfovibrio gigas under
      fermentative and respiratory conditions.
AB  - The sulfate-reducing bacterium Desulfovibrio gigas accumulates large amounts of
      polyglucose as an endogenous carbon and energy reserve. In the absence of
      exogenous substrates, the intracellular polysaccharide was utilized, and energy
      was conserved in the process (H. Santos, P. Fareleira, A. V. Xavier, L. Chen, M.
      Y. Liu, and J. LeGall, Biochem. Biophys. Res. Commun. 195:551-557, 1993). When an
      external electron acceptor was not provided, degradation of polyglucose by cell
      suspensions of D. gigas yielded acetate, glycerol, hydrogen, and ethanol. A
      detailed investigation of the metabolic pathways involved in the formation of
      these end products was carried out, based on measurements of the activities of
      glycolytic enzymes in cell extracts, by either spectrophotometric or nuclear
      magnetic resonance (NMR) assays. All of the enzyme activities associated with the
      glycogen cleavage and the Embden-Meyerhof pathway were determined as well as
      those involved in the formation of glycerol from dihydroxyacetone phosphate
      (glycerol-3-phosphate dehydrogenase and glycerol phosphatase) and the enzymes
      that catalyze the reactions leading to the production of ethanol (pyruvate
      decarboxylase and ethanol dehydrogenase). The key enzymes of the Entner-Doudoroff
      pathway were not detected. The methylglyoxal bypass was identified as a second
      glycolytic branch operating simultaneously with the Embden-Meyerhof pathway. The
      relative contribution of these two pathways for polyglucose degradation was 2:3.
      13C-labeling experiments with cell extracts using isotopically enriched glucose
      and 13C-NMR analysis supported the proposed pathways. The information on the
      metabolic pathways involved in polyglucose catabolism combined with analyses of
      the end products formed from polyglucose under fermentative conditions provided
      some insight into the role of NADH in D. gigas. In the presence of electron
      acceptors, NADH resulting from polyglucose degradation was utilized for the
      reduction of sulfate, thiosulfate, or nitrite, leading to the formation of
      acetate as the only carbon end product besides CO2. Evidence supporting the role
      of NADH as a source of reducing equivalents for the production of hydrogen is
      also presented.

PMID- 9190815
TI  - Translation of the leaderless Caulobacter dnaX mRNA.
AB  - The expression of the Caulobacter crescentus homolog of dnaX, which in
      Escherichia coli encodes both the gamma and tau subunits of the DNA polymerase
      III holoenzyme, is subject to cell cycle control. We present evidence that the
      first amino acid in the predicted DnaX protein corresponds to the first codon in
      the mRNA transcribed from the dnaX promoter; thus, the ribosome must recognize
      the mRNA at a site downstream of the start codon in an unusual but not
      unprecedented fashion. Inserting four bases in front of the AUG at the 5' end of
      dnaX mRNA abolishes translation in the correct frame. The sequence upstream of
      the translational start site shows little homology to the canonical Shine
      Dalgarno ribosome recognition sequence, but the region downstream of the start
      codon is complementary to a region of 16S rRNA implicated in downstream box
      recognition. The region downstream of the dnaX AUG, which is important for
      efficient translation, exhibits homology with the corresponding region from the
      Caulobacter hemE gene adjacent to the replication origin. The hemE gene also
      appears to be translated from a leaderless mRNA. Additionally, as was found for
      hemE, an upstream untranslated mRNA also extends into the dnaX coding sequence.
      We propose that translation of leaderless mRNAs may provide a mechanism by which
      the ribosome can distinguish between productive and nonproductive templates.

PMID- 9190816
TI  - Mutations in sdh (succinate dehydrogenase genes) alter the thiamine requirement
      of Salmonella typhimurium.
AB  - Mutants lacking the first enzyme in de novo purine synthesis (PurF) can
      synthesize thiamine if increased levels of pantothenate are present in the
      culture medium (J. L. Enos-Berlage and D. M. Downs, J. Bacteriol. 178:1476-1479,
      1996). Derivatives of purF mutants that no longer required pantothenate for
      thiamine-independent growth were isolated. Analysis of these mutants demonstrated
      that they were defective in succinate dehydrogenase (Sdh), an enzyme of the
      tricarboxylic acid cycle. Results of phenotypic analyses suggested that a defect
      in Sdh decreased the thiamine requirement of Salmonella typhimurium. This reduced
      requirement correlated with levels of succinyl-coenzyme A (succinyl-CoA), which
      is synthesized in a thiamine pyrophosphate-dependent reaction. The effect of
      succinyl-CoA on thiamine metabolism was distinct from the role of pantothenate in
      thiamine synthesis.

PMID- 9190817
TI  - A genetic locus involved in iron utilization unique to some Campylobacter
      strains.
AB  - Two genes involved in iron utilization in Campylobacter coli VC167 T1 have been
      characterized. The cfrA gene encodes a protein with a predicted Mr of 77,653
      which, after processing of the leader sequence, has a predicted Mr of 75,635.
      This protein has significant sequence identity to siderophore receptors of
      several bacteria, and site-specific mutants defective in cfrA do not synthesize
      one of two major iron-repressible outer membrane proteins. An adjacent gene
      encodes a TonB-like protein; a mutant in this gene lost the ability to utilize
      hemin, ferrichrome, and enterochelin as iron sources. The cfrA and tonB genes of
      VC167 T1 hybridized to all strains of C. coli and most strains of C. jejuni
      examined but did not hybridize to several other strains of C. jejuni, suggesting
      that the thermophilic campylobacters can be separated into two categories based
      on the presence of these two iron utilization genes.

PMID- 9190818
TI  - Comparative characterization of SecA from the alpha-subclass purple bacterium
      Rhodobacter capsulatus and Escherichia coli reveals differences in membrane and
      precursor specificity.
AB  - We have cloned the secA gene of the alpha-subclass purple bacterium Rhodobacter
      capsulatus, a close relative to the mitochondrial ancestor, and purified the
      protein after expression in Escherichia coli. R. capsulatus SecA contains 904
      amino acids with 53% identity to E. coli and 54% identity to Caulobacter
      crescentus SecA. In contrast to the nearly equal partitioning of E. coli SecA
      between the cytosol and plasma membrane, R. capsulatus SecA is recovered
      predominantly from the membrane fraction. A SecA-deficient, cell-free synthesis
      translocation system prepared from R. capsulatus is used to demonstrate
      translocation activity of the purified R. capsulatus SecA. This translocation
      activity is then compared to that of the E. coli counterpart by using various
      precursor proteins and inside-out membrane vesicles prepared from both bacteria.
      We find a preference of the R. capsulatus SecA for the homologous membrane
      vesicles whereas E. coli SecA is active with either type of membrane.
      Furthermore, the two SecA proteins clearly select between distinct precursor
      proteins. In addition, we show here for the first time that a bacterial c-type
      cytochrome utilizes the canonical, Sec-dependent export pathway.

PMID- 9190819
TI  - Localized frameshift mutation generates selective, high-frequency phase variation
      of a surface lipoprotein encoded by a mycoplasma ABC transporter operon.
AB  - The wall-less mycoplasmas have revealed unusual microbial strategies for adaptive
      variation of antigenic membrane proteins exposed during their surface
      colonization of host cells. In particular, high-frequency mutations affecting the
      expression of selected surface lipoproteins have been increasingly documented for
      this group of organisms. A novel manifestation of mutational phase variation is
      shown here to occur in Mycoplasma fermentans, a chronic human infectious agent
      and possible AIDS-associated pathogen. A putative ABC type transport operon
      encoding four gene products is identified. The 3' distal gene encoding P78, a
      known surface-exposed antigen and the proposed substrate-binding lipoprotein of
      the transporter, is subject to localized hypermutation in a short homopolymeric
      tract of adenine residues located in the N-terminal coding region of the mature
      product. High-frequency, reversible insertion/deletion frameshift mutations lead
      to selective phase variation in P78 expression, whereas the putative nucleotide
      binding protein, P63, encoded by the most 5' gene of the operon, is continually
      expressed. Mutation-based phase variation in specific surface-exposed microbial
      transporter components may provide an adaptive advantage for immune evasion,
      while continued expression of other elements of the same transporter may preserve
      essential metabolic functions and confer alternative substrate specificity. These
      features could be critical in mycoplasmas, where limitations in both
      transcriptional regulators and transport systems may prevail. This study also
      documents that P63 contains an uncharacteristic hydrophobic sequence between
      predicted nucleotide binding motifs and displays an amphiphilic character in
      detergent fractionation. Both features are consistent with an evolutionary
      adaptation favoring integral association of this putative energy-transducing
      component with the single mycoplasma membrane.

PMID- 9190820
TI  - Stereochemical course of two arene-cis-diol dehydrogenases specifically induced
      in Pseudomonas putida.
AB  - Catabolism of nonphenolic arenes is frequently initiated by dioxygenases,
      yielding single isomer products with two adjacent hydroxylated asymmetric
      centers. The next enzymic reaction dehydrogenates these cyclic cis-diols, with
      aromatization yielding catechols for ring cleavage. There are two stereochemical
      questions to answer. (i) To which face of NAD is hydride transferred giving NADH?
      (ii) Which hydrogen of the arene-cis-diols is donated to NAD? We report the
      results of 1H nuclear magnetic resonance [1H NMR] experiments for two diol
      dehydrogenases induced during growth of Pseudomonas putida PaW1(TOL) and JT105
      with p-xylene and p-toluate, respectively. per-[2H5]benzoate-1,2-dihydrodiol and
      per-[2H7]- and specifically [2H]p-toluate-2,3-dihydrodiols were the substrates
      used to examine this by 1H NMR, as the two protons of the prochiral center (C-4
      of the nicotinamide ring) are easily distinguished in the region of 2.6 to 2.7
      ppm. We found that with the partially purified dehydrogenases (i) 2H from the
      (2R) center of per-(1S,2R)-benzoate-1,2-dihydrodiol was donated to the Si-face of
      NAD to give (4S)-NAD2H; (ii) p-toluate-2,3-diol dehydrogenase also provided
      exclusively (4S)-NAD2H, but the 2H was transferred from both the 2- and 3-C atoms
      of (2S,3R)-p-toluate-2,3-dihydrodiol with specifically deuterated species in
      approximately equal amounts; and (iii) the unexpected lack of stereo- and
      regioselectivity of p-toluate-2,3-diol dehydrogenase was supported by kinetic
      isotope effect studies.

PMID- 9190821
TI  - Genetic analysis of second-site revertants of bacteriophage lambda integrase
      mutants.
AB  - Bacteriophage lambda site-specific recombination is catalyzed by the phage
      encoded integrase (Int) protein. Using a collection of 21 recombination-defective
      Int mutants, we performed a second-site reversion analysis. One of the primary
      mutants contained a valine-to-glutamic acid change at position 175 (V175E), and a
      pseudorevertant with a lysine change at this site (V175K) was also isolated.
      Relative to the wild-type protein, the V175E protein was defective in its ability
      to form the attL complex and to catalyze excision in vivo and in vitro. A mutant
      containing an alanine substitution (V175A) was made by site-directed mutagenesis,
      and it was more efficient than the V175K protein in forming the attL complex and
      promoting excision. These results indicate that a nonpolar side chain at residue
      175 is required for function. The second primary mutant contained a proline-to
      leucine change at position 243 (P243L). A true second-site revertant was isolated
      that contained a glutamic acid-to-lysine change (E218K). The P243L-E218K protein
      promoted recombination and bound arm-type sites more efficiently than the
      original P243L protein but not as efficiently as the protein containing the E218K
      substitution alone. The E218K substitution also restored activity to a mutant
      with a threonine-to-isoleucine substitution at position 270 (T270I). This result
      showed that suppression by the E218K change is not allele specific and suggests
      that the substitution improves an inherent activity of Int rather than directly
      compensating for the defect caused by the primary substitutions. Results with
      challenge phages carrying attL sites with altered core sites indicate that the
      E218K change may improve binding to the core site.

PMID- 9190823
TI  - Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio
      harveyi.
AB  - Different species of bacteria were tested for production of extracellular
      autoinducer-like activities that could stimulate the expression of the
      luminescence genes in Vibrio harveyi. Several species of bacteria, including the
      pathogens Vibrio cholerae and Vibrio parahaemolyticus, were found to produce such
      activities. Possible physiological roles for the two V. harveyi detection
      response systems and their joint regulation are discussed.

PMID- 9190822
TI  - Multiple transcribed elements control expression of the Escherichia coli btuB
      gene.
AB  - Repression by vitamin B12 of the cobalamin transport protein BtuB in the outer
      membrane of Escherichia coli operates at both the transcriptional and
      translational levels and is controlled by transcribed sequences within the leader
      and proximal portion of the btuB coding sequence. The effects of deletions from
      either end of this region on repression and expression were determined with lac
      fusions. An element at the 5' end of the transcript and the putative attenuator
      within the coding sequence were required for transcriptional repression. The
      presence of either element caused a marked reduction in btuB-lacZ expression
      which was reversed by the presence of a conserved sequence element in the leader,
      suggesting the importance of long-range interactions in the btuB leader for
      expression and regulation.

PMID- 9190824
TI  - Identification of the ahp operon of Salmonella typhimurium as a macrophage
      induced locus.
AB  - Previously, we tagged a macrophage-induced Salmonella typhimurium locus with
      Mudlux (K. P. Francis and M. P. Gallagher, Infect. Immun. 61:640-649, 1993). The
      insertion lies within the OxyR-regulated ahpC locus and conveys alkyl peroxide
      sensitivity. Plasmid-encoded ahp reverses sensitivity but reduces luminescence.
      This suggests that OxyR is titrated by the multicopy ahp promoter.

PMID- 9190825
TI  - Isolation and expression of the catA gene encoding the major vegetative catalase
      in Streptomyces coelicolor Muller.
AB  - We isolated the catA gene for the major vegetative catalase from Streptomyces
      coelicolor Muller. It encodes a polypeptide of 488 residues (55,440 Da) that is
      highly homologous to typical monofunctional catalases. We investigated catA
      expression by analyzing both catA mRNA and catalase activity. catA expression was
      increased by H2O2 treatment but did not increase during stationary phase. A
      putative catalase (CatB) cross-reactive with anti-CatA antibody appeared during
      stationary phase and in the aerial mycelium.

PMID- 9190826
TI  - Acyl-acyl carrier protein is a donor of fatty acids in the NodA-dependent step in
      biosynthesis of lipochitin oligosaccharides by rhizobia.
AB  - NodA controls transfer of a fatty acid in the biosynthesis of lipochitin
      oligosaccharides by rhizobia. In an in vitro assay, we used de-N-acetylated
      chitin oligosaccharides substituted with an O-acetyl moiety as acyl acceptor
      substrates. We show that acyl-acyl carrier protein is used as a donor in NodA
      directed fatty acid transfer.

PMID- 9190827
TI  - Characterization of the L-malate permease gene (maeP) of Streptococcus bovis ATCC
      15352.
AB  - A gene which was shown to be cotranscribed with the NAD+-dependent malic enzyme
      gene (maeE) of Streptococcus bovis ATCC 15352 was revealed to encode L-malate
      specific permease (MaeP), which showed high activity at low pHs (pH 5.1 to 5.9).
      MaeP was strongly inhibited by the ionophores nigericin and valinomycin.

PMID- 9190828
TI  - A putative monofunctional glycosyltransferase is expressed in Ralstonia eutropha.
AB  - A gene, mgt, encoding a protein homologous to the N-terminal module of class A
      high-molecular-mass penicillin-binding proteins was identified in Ralstonia
      eutropha. By using specific antibodies, the corresponding Mgt protein was
      detected in association with the membrane, confirming that the N-terminal
      hydrophobic segment functioned as a membrane anchor. A derivative in which the
      hydrophobic sequence was deleted was overexpressed as a maltose-binding fusion
      protein in Escherichia coli. Cleavage of the product resulted in substantial
      amounts of soluble Mgt derivative, indicating that folding occurs independently
      on other proteins or on homologous domains of penicillin-binding proteins.

PMID- 9190829
TI  - Structural studies of malate dehydrogenases (MDHs): MDHs in Brevundimonas species
      are the first reported MDHs in Proteobacteria which resemble lactate
      dehydrogenases in primary structure.
AB  - The N-terminal sequences of malate dehydrogenases from 10 bacterial strains,
      representing seven genera of Proteobacteria, were determined. Of these, the
      enzyme sequences of species classified in the genus Brevundimonas clearly
      resembled those malate dehydrogenases with greatest similarity to lactate
      dehydrogenases. Additional evidence from subunit molecular weights, peptide
      mapping, and enzyme mobilities suggested that malate dehydrogenases from species
      of the genus Brevundimonas were structurally distinct from others in the study.

PMID- 9190831
TI  - A signal transducer for aerotaxis in Escherichia coli.
AB  - The newly discovered aer locus of Escherichia coli encodes a 506-residue protein
      with an N terminus that resembles the NifL aerosensor and a C terminus that
      resembles the flagellar signaling domain of methyl-accepting chemoreceptors.
      Deletion mutants lacking a functional Aer protein failed to congregate around air
      bubbles or follow oxygen gradients in soft agar plates. Membranes with
      overexpressed Aer protein also contained high levels of noncovalently associated
      flavin adenine dinucleotide (FAD). We propose that Aer is a flavoprotein that
      mediates positive aerotactic responses in E. coli. Aer may use its FAD prosthetic
      group as a cellular redox sensor to monitor environmental oxygen levels.

PMID- 9190830
TI  - Identification and DNA sequence of the mobilization region of the 5
      nitroimidazole resistance plasmid pIP421 from Bacteroides fragilis.
AB  - The nucleotide sequence of the DNA mobilization region of the 5-nitroimidazole
      resistance plasmid pIP421, from strain BF-F239 of Bacteroides fragilis, was
      determined. It contains a putative origin of transfer (oriT) including three sets
      of inverted repeats and two sequences reminiscent of specific integration host
      factor binding sites. The product of the mobilization gene mob421 (42.2 kDa) is a
      member of the Bacteroides mobilization protein family, which includes the MobA of
      pBI143, NBUs, and Tn4555. Sequence similarity suggests that it has both oriT
      binding and nicking activities. The transfer frequency of pIP421 in a B. fragilis
      donor strain possessing a Tc(r) or Tc(r) Em(r)-like conjugative transposon was
      significantly enhanced by tetracycline. Moreover, the mobilization region of
      pIP421 confers the ability to be mobilized from Escherichia coli by an IncP
      plasmid.

PMID- 9190832
TI  - Differential reinforcement of low rate performance, pharmacokinetics and
      pharmacokinetic-pharmacodynamic modeling: independent interaction of alprazolam
      and caffeine.
AB  - To investigate the interaction between alprazolam and caffeine, performance on a
      differential reinforcement of low-rate behavior schedule and the respective
      pharmacokinetics (PK) were explored in concurrent studies. Alprazolam PK was not
      altered by caffeine, but alprazolam retarded caffeine absorption indirectly, as
      inferred by the lack of i.v. drug administration PK interaction, thereby
      decreasing serum methylxanthine concentrations. Inasmuch as alprazolam was more
      potent and short-lived than caffeine in decreasing the reinforcement rate
      (consonant with their respective t(1/2) values, 0.44 and 3.1 hr), the
      alprazolam/caffeine potency ratio decreased across the session time, which
      determined the expression of the combined effects. Thus, the decreased
      methylxanthine level yielded slightly less disruption in performance for the
      observed combined effect, compared to the expected calculated effect, only near
      the end of a session. The interaction was PK linked and mainly not
      distinguishable from independence as indicated by the Poch dose-response curve
      method and the integration of PK and pharmacodynamics. The sigmoid maximal effect
      link pharmacodynamic model indicated that caffeine did not alter the
      concentration at half of the maximal effect value of alprazolam and suggested
      that the interaction is not competitive, but independent. Although the nature of
      the benzodiazepine-methylxanthine interaction has been controversial in other
      behavioral studies, as is the role of PK in determining behavior, this and our
      previous study make it evident that the interaction is independent not only
      across doses and routes of administration, but also with respect to two indices
      of differential reinforcement of low rate performance.

PMID- 9190833
TI  - Cannabinoid-induced hypotension and bradycardia in rats mediated by CB1-like
      cannabinoid receptors.
AB  - Previous studies indicate that the CB1 cannabinoid receptor antagonist, N
      (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-met hyl-1H-pyrazole
      3-carboxamide HCl (SR141716A), inhibits the anandamide- and delta9
      tetrahydrocannabinol- (THC) induced hypotension and bradycardia in anesthetized
      rats with a potency similar to that observed for SR141716A antagonism of THC
      induced neurobehavioral effects. To further test the role of CB1 receptors in the
      cardiovascular effects of cannabinoids, we examined two additional criteria for
      receptor-specific interactions: the rank order of potency of agonists and
      stereoselectivity. A series of cannabinoid analogs including the enantiomeric
      pair (-)-11-OH-delta9-THC dimethylheptyl (+)-11-OH-delta9-THC dimethylheptyl were
      evaluated for their effects on arterial blood pressure and heart rate in urethane
      anesthetized rats. Six analogs elicited pronounced and long lasting hypotension
      and bradycardia that were blocked by 3 mg/kg of SR141716A. The rank order of
      potency was (-)-11-OH-delta9-THC dimethylheptyl > or = (-)-3-[2-hydroxy-4-(1,1
      dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]c yclohexan-1-ol > (-)-3-[2-hydroxy-4
      (1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy-propyl]c yclohexan-1-ol > THC >
      anandamide > or = (-)-3-[2-hydroxy-4-(1,1-dimethyl-heptyl)phenyl]-4-[3-hydroxy
      propyl]c yclohexan-1-ol, which correlated well with CB1 receptor affinity or
      analgesic potency (r = 0.96-0.99). There was no hypotension or bradycardia after
      palmitoylethanolamine or (+)-11-OH-delta9-THC dimethylheptyl. An initial pressor
      response was also observed with THC and anandamide, which was not antagonized by
      SR141716A. We conclude that the similar rank orders of potency, stereoselectivity
      and sensitivity to blockade by SR141716A indicate the involvement of CB1-like
      receptors in the hypotensive and bradycardic actions of cannabinoids, whereas the
      mechanism of the pressor effect of THC and anandamide remains unclear.

PMID- 9190834
TI  - Beta adrenergic receptor stimulated prostacyclin synthesis in rabbit coronary
      endothelial cells is mediated by selective activation of phospholipase D:
      inhibition by adenosine 3'5'-cyclic monophosphate.
AB  - Activation of beta adrenergic receptors in the isolated rabbit heart by
      catecholamines stimulates prostacyclin (PGI2) synthesis, which is inhibited by
      adenosine 3'5'-cyclic monophosphate (cAMP). The purpose of this study was to
      determine if activation of beta adrenergic receptors in cultured coronary
      endothelial cells (CEC) of rabbit heart with isoproterenol (ISOP) stimulates PGI2
      synthesis and if cAMP inhibits the synthesis of this prostanoid and to
      investigate the underlying mechanism. Incubation of CEC with ISOP increased
      production of cAMP and PGI2, measured as immunoreactive cAMP and 6-keto
      prostaglandin F1alpha, (6-keto-PGF1alpha), respectively. Forskolin, an activator
      of adenylyl cyclase, increased cAMP accumulation and inhibited ISOP-stimulated 6
      keto-PGF1alpha synthesis. 8-(4-chlorophenyl-thio) cAMP also inhibited ISOP
      induced 6-keto-PGF1alpha production. However, miconazole, an inhibitor of
      adenylyl cyclase, reduced cAMP accumulation and enhanced ISOP-stimulated 6-keto
      PGF1alpha synthesis in CEC. ISOP-induced 6-keto-PGF1alpha synthesis was
      attenuated by C2-ceramide, an inhibitor of phospholipase D (PLD) by propranolol,
      a beta-AR antagonist that also inhibits phosphatidate phosphohydrolase and by the
      diacylglycerol lipase inhibitor 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane
      (RHC 80267). Acetylcholine (ACh) induced 6-keto-PGF1alpha synthesis was also
      inhibited by these agents. Both ISOP and ACh increased PLD activity, which was
      inhibited by C2-ceramide but not by RHC 80267 or propranolol. ACh but not ISOP
      increased phospholipase A2 activity in CEC. ISOP- but not ACh-induced increase in
      PLD activity was attenuated by forskolin and 8-(4-chlorophenyl-thio)-adenosine 3'
      5'-cyclic monophosphate and augmented by miconazole. These data suggest that beta
      adrenergic receptors activation promotes PGI2 synthesis in the CEC by selective
      activation of PLD and that cAMP decreases PGI2 synthesis by decreasing PLD
      activity. Moreover, beta adrenergic receptors activated PLD appears to be
      distinct from that stimulated by ACh.

PMID- 9190835
TI  - Differences in platelet-activating factor receptor mediated Ca++ response between
      hamster and guinea pig alveolar macrophages.
AB  - The different platelet-activating factor (PAF) receptor subtypes were identified
      in alveolar macrophages of hamster and guinea pig, based on the distinct
      characteristics of PAF-induced Ca++ responses and PAF antagonist potencies to
      these responses. PAF, but not lyso-PAF (inactive PAF), induced Ca++ release from
      intracellular Ca++ stores and the influx of extracellular Ca++ in a dose
      dependent manner in both hamster and guinea pig alveolar macrophages. The potency
      for PAF-stimulated Ca++ release, however, was significantly different between the
      two species with EC50 values being 30- and 50-fold higher in Ca++ release and
      Ca++ influx responses in guinea pig than hamster, respectively. In addition,
      there were distinct differences in Ca++ influx characteristics between the two
      species; guinea pig macrophages exhibiting a rapid Ca++ extrusion and high
      sensitivity to thapsigargin (depletion of intracellular Ca++ store). The PAF
      induced Ca++ response was sensitive to G-protein inhibitor pertussis toxin in
      hamster but not in guinea pig, suggesting the coupling of different types of G
      proteins to PAF receptors. Pretreatment of macrophages with tyrosine kinase
      inhibitor, herbimycin A, caused a dose-dependent decrease in PAF-induced Ca++
      response in guinea pig but surprisingly an increased response in hamster. These
      observations suggest the possibility of a dual mechanism, for G-protein and
      tyrosine kinase, in PAF-induced phospholipase C activation of macrophages from
      both species and thus Ca++ signaling in response to PAF-mediated receptor signal
      transduction cascade. The PAF-induced Ca++ response was desensitized by
      repetitive stimulation with PAF or pretreatment with protein kinase C activator,
      mitogen-activated protein kinase, which had a slightly greater potency in guinea
      pig than hamster. Importantly, three structurally distinct PAF antagonists,
      WEB2086, L659,989 and CL184005, blocked PAF-induced Ca++ responses in a dose
      dependent manner with a markedly different potencies between the two species. The
      IC50 values for inhibiting PAF-induced Ca++ release were 2.5- (WEB2086), 650-
      (L659,989) and 120- (CL184005) fold less in hamster than in guinea pig. The
      relative potencies of these PAF antagonists in hamster macrophages were L659,989
      > CL184005 > WEB2086. However, in guinea pig these three antagonists showed
      roughly the same potency. Interestingly, the opposite inhibitory effects of these
      antagonists on PAF-induced Ca++ influx were found in the two species, in which
      the IC50 were 15- (WEB2086) and 5- (CL184005) fold greater in hamster than in
      guinea pig but no difference in the IC50 value of L659,989 between the two
      species. Pretreatment of macrophages from both species with these antagonists had
      no effect on ATP-induced Ca++ response, suggesting that the antagonism is
      specific to PAF receptors. Based on our data, it was concluded that the alveolar
      macrophages isolated from the bronchoalveolar lavage of hamsters contain a
      distinct subtype PAF receptor that differs from that of guinea pigs in modulating
      a different signal transduction pathway.

PMID- 9190836
TI  - alpha-Ketoglutarate transport in rat renal brush-border and basolateral membrane
      vesicles.
AB  - The dicarboxylate, alpha-ketoglutarate (alphaKG), has been identified as the most
      likely physiological anion involved in renal proximal tubule basolateral membrane
      (BLM) dicarboxylate/organic anion exchange. In the present study, we
      characterized the uptake of alphaKG in BLM and brush-border membrane (BBM)
      vesicles isolated from rat kidney. In both membrane preparations, alphaKG uptake
      was Na+-dependent, saturable, electrogenic and inhibited by Li+. The initial rate
      of alphaKG (5 microM) uptake in BLM vesicles was twice that in BBM vesicles (258
      +/- 8.2 vs. 126 +/- 3.9 pmol/mg/5 sec). The BLM transporter had a high affinity
      for alphaKG (apparent Km = 15.2 microM), but a relatively low transport capacity
      (Vmax = 386 pmol/mg/5 sec). In contrast, the BBM transporter had characteristics
      of a low-affinity (Km = 158 microM), high-capacity (Vmax = 1106 pmol/mg/5 sec)
      system. Other dicarboxylates such as succinate, malate, fumarate and glutarate at
      a concentration of 1 mM inhibited alphaKG uptake into BLM and BBM vesicles to the
      same extent (>90%). The tricarboxylate, citrate, also inhibited alphaKG uptake
      (70-80%). However, of these Krebs' cycle intermediates, only alphaKG and
      glutarate were able to affect p-aminohippurate (PAH) uptake into BLM vesicles.
      These results lend further support for a BLM PAH/alphaKG exchanger. Furthermore,
      if extracellular alphaKG plays a role in the operation of the PAH/alphaKG
      exchanger, the high-affinity Na+-dependent alphaKG transporter located in the BLM
      is the likely source of the organic anion.

PMID- 9190837
TI  - Nonpeptide angiotensin II antagonist losartan inhibits thromboxane A2-induced
      contractions in canine coronary arteries.
AB  - We investigated the selectivity of a nonpeptide angiotensin II AT1 receptor
      antagonist losartan for the vascular thromboxane A2 (TxA2)/prostaglandin
      endoperoxide (PGH2) receptor in canine coronary arteries. Isometric tension was
      measured in canine coronary artery rings suspended in organ chambers perfused
      with 95% O2/5% CO2. The TxA2 analog, U46619, produced dose-dependent
      vasoconstdction in coronary rings (EC50, 10.6 +/- 0.9 nmol/l). Pretreatment with
      losartan (10(-8)-10(-5) mol/l) inhibited the contractile response of U46619 and
      shifted the concentration-response curve to the right in dose-dependent manner.
      The EC50 of U46619 was increased 3- and 13-fold in the presence of both 1 and 10
      micromol/l of losartan without a change in maximal contraction. The selective
      TxA2/PGH2 receptor antagonist SQ29548 blocked U46619-induced contraction with
      greater potency than losartan in isolated coronary arteries. The active
      metabolite of losartan EXP3174 at 1 micromol/l did competitively block U46619
      induced contractions in canine coronary rings. In contrast, the contractile
      responses produced by U46619 were unaffected by exposure to the nonpeptide AT1
      receptor antagonist CV11974, the AT2 receptor antagonist PD123319 or the
      nonselective peptide angiotensin II antagonist Sar1Thr8-Ang II, each at 1
      micromol/l concentration. These data indicate that losartan and its active
      metabolite EXP3174 are antagonists to the TxA2/PGH2 receptor in canine coronary
      arteries. The antagonistic effect of losartan and EXP3174 on the vascular TxA2/
      PGH2 receptor may contribute to the long-term blood pressure-lowering effects of
      angiotensin antagonists in hypertension.

PMID- 9190838
TI  - Excretion and metabolism of propionyl-L-carnitine in the isolated perfused rat
      kidney.
AB  - Propionyl-L-carnitine (PLC) is an ester of L-carnitine (LC) under evaluation for
      the treatment of cardiovascular disorders. The renal disposition of PLC was
      studied in the isolated perfused rat kidney with deuterium-labeled derivative
      (PLC-CD3). Kidneys of male Sprague-Dawley rats were perfused at initial PLC-CD3
      concentrations of 10 (n = 4) and 200 microM (n = 5). High-performance liquid
      chromatography/mass spectrometry was used to quantify PLC-CD3, deuterated L
      carnitine (LC-CD3) and acetyl-L-carnitine (ALC-CD3) in perfusate and urine. PLC
      CD3 in perfusate decreased in a monoexponential manner with a half-life of 90 +/-
      24 min (S.D.) (10 microM) and 94 +/- 11 min (200 microM). The renal excretory
      clearance of PLC-CD3 was significantly lower (P < .05, unpaired t test) at an
      initial concentration of 10 microM (45 +/- 23 microl/min) than at 200 microM (85
      +/- 28 microl/min), but in both cases it was substantially less than the
      glomerular filtration rate, which indicates extensive tubular reabsorption. The
      renal excretory clearance of PLC-CD3 represented less than 6% of the total
      clearance, which suggests that metabolism is the major renal elimination route
      for this compound. The appearance in perfusate and urine of LC-CD3 and ALC-CD3
      provided additional evidence for a metabolic role of the kidney. The apparent
      renal excretory clearance values for these metabolites were always significantly
      higher than the values obtained for the corresponding endogenous compounds, which
      suggests that LC-CD3 and ALC-CD3, as formed metabolites, underwent passive or
      carrier-mediated movement directly into urine.

PMID- 9190839
TI  - Possible mechanism of palytoxin-induced Ca++ mobilization in porcine coronary
      artery.
AB  - We investigated the mechanisms involved in palytoxin (PTX)-induced cytosolic Ca++
      ([Ca++]i) mobilization and contraction in porcine coronary arteries using a
      fluorescent Ca++ indicator fura-PE3. PTX (1 pM-10 nM) induced concentration
      dependent and sustained increases in [Ca++]i and tension, both of which were
      partially inhibited by 10 microM verapamil or 1 microM nicardipine. In Ca++-free
      solution containing 1 mM EGTA, PTX did not increase [Ca++]i. In nominally Ca++
      free solution (no EGTA), however, PTX increased [Ca++]i, which was presumed to be
      due to release of Ca++ from intracellular stores. PTX-induced rise in [Ca++]i was
      dependent on external Na+ because it did not increase [Ca++]i in Na+-free
      solutions containing verapamil. An increase in [Ca++]i in response to 65.4 mM KCl
      also involved a verapamil-resistant but external Na+-dependent component. After
      blockage of voltage-dependent Ca++ channels with verapamil, elevation of external
      K+ to 65.4 mM enhanced the responses of [Ca++]i and tension to PTX. PTX at 10 and
      100 pM depolarized the membrane by 4.5 +/- 0.8 and 18.6 +/- 1.7 mV, respectively.
      Because PTX is known to increase membrane Na+ permeability, our results suggest
      that an increase in cytosolic Na+ and the depolarization were primary events
      required for the PTX-induced Ca++ mobilization and that Ca++ influxes through
      voltage-dependent Ca++ channels and Na+-Ca++ exchange and Ca++ release from Ca++
      stores, which was triggered by increased Ca++ entry, were responsible for the PTX
      induced increase in [Ca++]i.

PMID- 9190840
TI  - Bioavailability, antinociceptive and antiinflammatory properties of BP 2-94, a
      histamine H3 receptor agonist prodrug.
AB  - (R)alpha-Methylhistamine [(R)alpha-MeHA], a potent and selective histamine H3
      receptor agonist in vitro and in vivo in rodents, was found to display
      comparatively low plasma level in healthy human volunteers, attributable to an
      extensive methylation of the drug's imidazole ring by histamine-N
      methyltransferase. To limit this inactivation process, BP 2-94, ie., (R)-(-)-2
      [[N-[1-(1H-imidazol-4-yl)-2-propyl]imino]phenylmethyl] phenol, was selected as a
      prodrug. A sensitive radioimmunoassay was developed to study the generation of
      (R)alpha-MeHA slowly released from BP 2-94 in vitro and in vivo by chemical
      hydrolysis. In mice after oral administration of BP 2-94 high levels of both
      prodrug and (R)alpha-MeHA were detected in plasma and various tissues except in
      the brain. In humans receiving 0.1 mmol BP 2-94 orally, plasma levels of (R)alpha
      MeHA-like immunoreactivity decayed with a t(1/2) more than 24 hr, the area under
      the curve being two orders of magnitude higher than after oral administration of
      (R)alpha-MeHA. BP 2-94 displayed antiinflammatory and antinociceptive properties
      in rodents, related to the H3 receptor stimulation. It dose-dependently inhibited
      capsaicin-induced plasma protein extravasation in many rat tissues with ED50s of
      0.6 to 14 micromol/kg p.o., and maximal reductions by 35 to 87%. BP 2-94 also
      reduced zymosan-induced paw swelling in mice with an ED50 of 1 micromol/kg p.o.
      and showed marked activity in the phenylbenzoquinone-induced writhing (ED50 =
      0.03 micromol/kg, p.o.) or formalin tests in mice, but not in the hot plate jump
      test. From its pharmacokinetics and pharmacological profile BP 2-94 appears to be
      a promising novel therapeutic agent in disorders such as asthma, migraine or a
      variety of inflammatory diseases and pain associated with these disorders.

PMID- 9190841
TI  - Partial agonism by 3alpha,21-dihydroxy-5beta-pregnan-20-one at the gamma
      aminobutyric acidA receptor neurosteroid site.
AB  - 3alpha,21-Dihydroxy-5alpha-pregnan-20-one (5alpha-THDOC) and 3alpha-hydroxy
      5alpha-pregnan-20-one (3alpha,5alpha-P) have full efficacy as allosteric
      modulators of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to sites
      on the gamma-aminobutyric acid (GABA) type A receptor complex (GRC). Relative to
      3alpha,5alpha-P and 5alpha-THDOC, 3alpha,21-dihydroxy-5beta-pregnan-20-one (5beta
      THDOC) has limited efficacy as an allosteric modulator of [35S]TBPS binding.
      Interactions between 3alpha,5alpha-P, 5alpha-THDOC and 5beta-THDOC were examined
      to determine whether these neuroactive steroids share a common site for
      modulation of the GRC. The concentration-response curves for both 3alpha,5alpha-P
      and 5alpha-THDOC modulation of [35S]TBPS binding to brain and recombinantly
      derived GRCs are shifted rightward in the presence of various concentrations of
      5beta-THDOC. Similarly, 5beta-THDOC modulates GABA-evoked Cl- currents with low
      efficacy and inhibits the potentiation of GABA-evoked Cl- currents by
      3alpha,5alpha-P. Furthermore, behavioral studies reveal that 5beta-THDOC
      antagonizes 3alpha,5alpha-P-induced loss of the righting reflex in mice at a dose
      that has no effect alone. These results represent the first demonstration of
      antagonist-like actions of a neuroactive steroid on the GRCs at levels ranging
      from the receptor to animal behavior and suggest the existence of partial agonist
      neurosteroids.

PMID- 9190842
TI  - Pharmacokinetics and pharmacodynamics of the enantiomers of gallopamil.
AB  - The pharmacokinetics and pharmacodynamics of the enantiomers of the calcium
      antagonist gallopamil have been investigated in six healthy volunteers. Each
      subject was studied on five occasions after receiving, in randomized order:
      placebo, 25 mg of (R)-gallopamil, 25 mg of (S)-gallopamil, 50 mg of pseudoracemic
      [25 mg of deuterated (S)-gallopamil and 25 mg of (R)-gallopamil] and 100 mg of
      (R)-gallopamil HCl orally. After separate administration, the apparent oral
      clearances of both enantiomers were similar [(R), 15.1 +/- 9.9 liters/min; (S),
      11.0 +/- 6.0 liters/min], indicating that gallopamil first-pass metabolism is not
      stereoselective. After coadministration, the apparent oral clearance of each
      enantiomers decreased [(R), 5.9 +/- 2.8 liters/min; (S), 5.8 +/- 2.66
      liters/min], suggesting that a partial saturation of first-pass metabolism occurs
      because the dose was twice as high than for the single enantiomers. Serum protein
      binding and renal elimination of gallopamil are stereoselective, favoring (S)
      gallopamil. Analysis of urine samples revealed a marked degree of
      stereoselectivity in the formation of O- and N-dealkyl metabolites. Because these
      showed opposite stereoselectivity, canceling out each other, the net result was
      no or only marginal stereoselectivity. Twenty-five milligrams of (S)-gallopamil
      prolonged the PR interval in all subjects; however, a greater effect was elicited
      by 50 mg of (RS)-gallopamil. (R)-Gallopamil (100 mg) did not significantly alter
      the PR interval, although higher concentrations were attained than after the
      pseudoracemate. Based on a consideration of (S)-gallopamil serum concentrations,
      a comparable relationship between (S)-gallopamil level and effect occurred after
      (S)- and (RS)-gallopamil, indicating that the pharmacological effect produced by
      the racemate could be totally accounted for by the higher concentrations of (S)
      gallopamil attained.

PMID- 9190843
TI  - Differential muscarinic receptor binding of acetylcholinesterase inhibitors in
      rat brain, human brain and Chinese hamster ovary cells expressing human
      receptors.
AB  - Displacement of muscarinic radioligands by the cholinesterase inhibitors
      parathion, paraoxon, physostigmine and phenyl saligenin cyclic phosphate was
      examined in rat cortex and brain stem, human cortex and brain stem, and in
      Chinese hamster ovary (CHO) cells expressing human M2 or M4 muscarinic
      acetylcholine receptors. None of the cholinesterase inhibitors tested
      significantly affected binding of the antagonist [3H]quinuclinidyl benzilate.
      However, the agonist [3H]oxotremorine-methiodide (3H]oxo-M) was displaced by all
      compounds tested in a differential manner. Parathion only marginally displaced
      [H]oxo-M binding with pKi values < 5 in all tissue or cell types. In rat brain
      paraoxon, physostigmine and phenyl saligenin cyclic phosphate displaced [3H]oxo-M
      with pKi values of 7.5, 7.0 and 6.1, respectively. The cholinesterase inhibitors
      displaced [3H]oxo-M in human brain at 15- to 250-fold higher concentrations, that
      is with pKi values of 6.3, 4.6 and 4.2, respectively. Maximal displacement of
      [3H]oxo-M varied between 25% and 95%, depending on the species and the compound.
      Human receptors in brain and in CHO cells were equally sensitive to displacement
      of [3H]oxo-M by parathion, physostigmine and phenyl saligenin cyclic phosphate.
      However, paraoxon displaced [3H]oxo-M at > or = 35-fold lower concentrations from
      human receptors in brain than in CHO cells. In conclusion, the data show that
      cholinesterase inhibitors interfere with agonist binding to muscarinic
      acetylcholine receptors. The species-selectivity of the displacement appears to
      result from differences between rat and human muscarinic acetylcholine receptors.
      In addition, for paraoxon marked differences exist between the sensitivity of
      human muscarinic acetylcholine receptors in brain tissue and of those expressed
      in clonal CHO cells.

PMID- 9190844
TI  - Anticonvulsant action of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline in
      immature rats: comparison with the effects on motor performance.
AB  - Anticonvulsant action of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline
      (NBQX), a competitive antagonist at non-N-methyl-D-aspartate receptors for
      excitatory amino acids, was studied in a model of cortical epileptic
      afterdischarges (ADs) in 12-, 18- and 25-day-old rat pups with implanted
      electrodes. Electrical stimulation of sensorimotor cortex was repeated four times
      with 20-min intervals, NBQX (in doses of 10, 30, 60 or 90 mg/kg i.p.) or solvent
      (dimethyl sulfoxide, 1 ml/kg i.p.) were injected 10 min after the first
      afterdischarge. Dimethyl sulfoxide did not change the phenomena recorded; NBQX
      shortened ADs or at least blocked progressive prolongation observed under control
      conditions. Intensity of movements accompanying stimulation decreased after NBQX,
      and clonic movements accompanying ADs were suppressed in a dose-dependent manner.
      The highest dose of NBQX disabled the animals; therefore, the action of this drug
      on motor skills was studied in another group of animals. Even the dose of 30
      mg/kg NBQX interfered with motor performance in 12- and 18-day-old rat pups, 25
      day-old rat pups were more resistant to this action. NBQX exhibited only moderate
      antiepileptic action (suppression of progressive lengthening of ADs) at doses
      where unwanted side effects were absent.

PMID- 9190845
TI  - The treatment of animal models of malaria with iron chelators by use of a novel
      polymeric device for slow drug release.
AB  - The hydrophilic desferrioxamine (DFO) and the lipophilic salicylaldehyde
      isonicotinoyl hydrazone (SIH) are iron chelators which inhibit in vitro
      proliferation of Plasmodium falciparum with similar potency (IC50 approximately
      20 microM in 24- to 48-h tests). The in vivo assessment of these drugs was
      performed on Swiss mice infected with Plasmodium vinckei petteri with novel modes
      of drug administration and release. The drugs were delivered postpatently either
      by multiple i.p. injections or by a single i.p. or s.c. insertion of a drug
      containing polymeric device which released most of the drug within 7 days at
      apparently first-order rates. A regimen of three daily i.p injections of 5 mg DFO
      for 3 consecutive days or a 70-mg dose of the drug given as an i.p. or s.c.
      polymer implant evoked similar delay and reduction in peak parasitemias and
      reduced mortality with no apparent signs of toxicity. Relatively faster, but
      otherwise similar results were obtained with the less hydrophilic SIH. In
      combination, the two drugs apparently potentiated each other. The polymeric
      devices were particularly useful for treating Plasmodium berghei K173-infected
      C57Bl mice, a suggested model of cerebral malaria, in which classical methods of
      DFO delivery were ineffective. The insertion of a 140-mg DFO-containing device on
      day 6 postinfection (parasitemia approximately 1%) led to a marked reduction in
      parasite proliferation, appearance of neurological sequelae and mortality of
      mice. Our studies indicate that polymeric devices for slow drug release might be
      highly advantageous for both hydrophilic and lipophilic drugs whose antimalarial
      efficacy might depend on the maintenance of sustained blood levels. The results
      obtained with slow-release devices have implications for malaria chemotherapy as
      well as for iron chelation therapy in iron overload conditions.

PMID- 9190846
TI  - Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols
      and anesthetics.
AB  - 5-Hydroxytryptamine type 2A receptors (5-HT2A) are G protein-coupled receptors
      that increase intracellular Ca2+ concentrations via activation of phospholipase C
      beta and elevation of myo-inositol-1,4,5-triphosphate levels. In the central
      nervous system, these receptors are involved in regulating sleep and alertness.
      We now report that ethanol inhibited (IC50 = 41 mM) 5-HT2A receptor-induced Ca2+
      dependent Cl- currents in Xenopus laevis oocytes. Pharmacologically relevant
      concentrations of other n-alcohols (propanol to octanol) also inhibited 5-HT
      responses; however, longer-chain alcohols (decanol, undecanol and dodecanol) had
      little or no effect. The protein kinase C inhibitor GF109203X and the nonspecific
      protein kinase inhibitor staurosporine abolished the inhibitory effects of
      ethanol and octanol on 5-HT2A receptors. GF109203X enhanced 5-HT2A receptor
      function when administered alone. In addition, the volatile anesthetics halothane
      and 1-chloro-1,2,2-trifluorocyclobutane decreased 5-HT2A responses in a
      concentration-dependent manner. The inhibitory effects of the volatile
      anesthetics were also attenuated in oocytes treated with GF109203X. The
      intravenous anesthetics propofol, ketamine, pentobarbital and etomidate did not
      affect 5-HT2A receptor function. The modulation of 5-HT2A receptor-dependent
      current was also investigated using two novel halogenated compounds that do not
      produce anesthesia. The nonanesthetic compound 2,3-chloro-octafluorobutane had no
      effects on 5-HT-induced currents; however, the nonanesthetic compound 1,2
      dichlorohexafluorocyclobutane had an inhibitory effect at lower concentrations
      than the predicted anesthetic concentration. Thus, 5-HT2A receptors are inhibited
      by alcohols and volatile anesthetics, and these actions are dependent on protein
      kinase C.

PMID- 9190847
TI  - Pharmacological control of the mevalonate pathway: effect on arterial smooth
      muscle cell proliferation.
AB  - The mevalonate (MVA) pathway is involved in cell proliferation. We investigated
      drugs acting at different enzymatic steps on rat aorta smooth muscle cell (SMC)
      proliferation. Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (0.1-10 microM) dose-dependently decreased (up to 90%) SMC
      proliferation. This effect was prevented by 100 microM MVA, 10 microM all-trans
      farnesol (F-OH) and 5 microM all-trans geranylgeraniol (GG-OH), precursors of
      protein prenyl groups, but not by 2-cis GG-OH, precursor of dolichols, squalene
      and ubiquinone. The same inhibitory effect was obtained with 6-fluoromevalonate
      (1-50 microM), an inhibitor of MVA-pyrophosphate decarboxylase. Partial recovery
      of cell proliferation was possible by all-trans F-OH and all-trans GG-OH, but not
      MVA. Squalestatin 1 (1-25 microM), a potent squalene synthase inhibitor, blocked
      cholesterol synthesis and slightly inhibited (21% decrease) SMC proliferation
      only at the highest tested concentration. NB-598 (1-10 microM), a potent squalene
      epoxidase inhibitor, blocked cholesterol synthesis without affecting SMC
      proliferation. Finally, the benzodiazepine peptidomimetic BZA-5B (10-100 microM),
      a specific inhibitor of protein farnesyltransferase, time- and dose-dependently
      decreased SMC proliferation (up to 62%) after 9 days. This effect of BZA-5B was
      prevented by MVA and all-trans GG-OH, but not by all-trans F-OH. SMC
      proliferation was not affected by the closely related compound BZA-7B, which does
      not inhibit protein farnesyltransferase. Altogether, these findings focus the
      role of the MVA pathway in cell proliferation and call attention to the
      involvement of specific isoprenoid metabolites, probably through farnesylated and
      geranylgeranylated proteins, in the control of this cellular event.

PMID- 9190848
TI  - Human pharmacology of the opioid neuropeptide dynorphin A(1-13).
AB  - We evaluated the human pharmacology of dynorphin A(1-13) and determined whether
      this peptide can modulate naloxone-precipitated withdrawal effects. Such
      information could help determine its receptor mechanism of action and whether
      dynorphin is useful for treating opioid dependence. Six opioid-experienced
      subjects participated in a within-subject, placebo-controlled design. There were
      two phases, each with four test sessions. In phase 1, volunteers who were not
      physically dependent were administered 0, 0.1, 0.32 and 1 mg/kg dynorphin (15-min
      i.v. infusion) in ascending order, and subjective, observer-rated and
      physiological effects were monitored. Dynorphin produced brief, dose-related
      increases in drug effect ratings with both good and bad drug effects reported by
      different subjects. There were no significant changes in pupil size, respiratory
      rate, skin temperature, heart rate or blood pressure, These data are consistent
      with preclinical findings that dynorphin has a short duration of action and does
      not primarily exert its direct effects through mu-opioid receptors. In four
      separate sessions of phase 2, acute morphine pretreatment (45 mg/70 kg i.m.) was
      followed 15 or 18 hr later by dynorphin (0 vs. 1 mg/kg, 15-min i.v.) and then
      naloxone (1 or 3 vs. 10 mg/70 kg, 5-min i.v.). Under these conditions, dynorphin
      weakly potentiated naloxone-precipitated withdrawal. These data contrast with
      those of previous preclinical studies showing dependence-attenuating effects of
      dynorphin and fail to support its use as an antiwithdrawal agent in humans.

PMID- 9190849
TI  - Analgesia by dihydrocodeine is not due to formation of dihydromorphine: evidence
      from nociceptive activity in rat thalamus.
AB  - Dihydrocodeine is increasingly used in slow-release preparations for the
      treatment of chronic pain on step 2 of the "analgesic ladder" of the World Health
      Organization. Dihydrocodeine is suggested to act after O-demethylation to
      dihydromorphine. To test this possibility, experiments were carried out on rats
      under urethane anesthesia in which nociceptive activity was evoked by electrical
      stimulation of afferent C fibers in the sural nerve and recorded from neurons in
      the ventrobasal complex of the thalamus. Dihydrocodeine administered by
      intravenous injection reduced the evoked nociceptive activity in a dose-dependent
      manner. Like morphine, dihydrocodeine was capable of completely suppressing the
      evoked activity. Maximum depression was caused by 2 mg/kg, and the ED50 is 0.47
      mg/kg. Naloxone (0.2 mg/kg) reversed the effect of dihydrocodeine (2 mg/kg). To
      inhibit O-demethylation of dihydrocodeine to dihydromorphine, metyrapone or
      cimetidine (50 mg/kg) was injected intraperitoneally 20 min before dihydrocodeine
      (1 and 2 mg/kg). This failed to markedly reduce the effect of dihydrocodeine.
      Dihydromorphine injected intravenously also reduced the evoked activity in a dose
      dependent way. Maximum depression occurred at a dose of 4 mg/kg, and the ED50 is
      0.97 mg/kg. Dihydrocodeine and dihydromorphine were equieffective when
      administered by intrathecal injection at a dose of 100 microg. It is concluded
      that dihydrocodeine causes analgesia independent of biotransformation to
      dihydromorphine.

PMID- 9190850
TI  - Characterization of alpha-2D adrenergic receptor subtypes in bovine ocular tissue
      homogenates.
AB  - The alpha-2 adrenergic receptors are known to be present in the mammalian eye and
      to mediate the effects of alpha-2 agonists used in the treatment of glaucoma.
      Little is known, however, regarding the relative densities of the three alpha-2
      subtypes in the various tissues of the eye. We used receptor binding experiments
      with the radioligand [3H]RX821002 to characterize the alpha-2 adrenergic
      receptors in three tissues of the bovine eye, the ciliary body, retinal pigment
      epithelium/choriocapillaris and iris. The K(D) values in the three tissues were
      similar (0.12-0.14 nM), and the Bmax values ranged from 100 fmol/mg of protein
      for the ciliary body and retinal pigment epithelium/choriocapillaris to 200
      fmol/mg of protein for the iris. The pharmacological characteristics of the alpha
      2 receptors in all three tissues of the bovine eye, as assessed by competition
      studies, were essentially identical and were similar to the characteristics of
      the alpha-2A/D receptors of the bovine neurosensory retina. The correlation
      coefficients between the logarithms of the Ki values for the three tissues and
      the neurosensory retina for nine adrenergic agents were .98 to .99. We conclude
      that the alpha-2 adrenergic receptors in the ciliary body, iris and retinal
      pigment epithelium/choriocapillaris of the bovine eye are mainly alpha-2D.

PMID- 9190851
TI  - Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in
      vivo: evidence that thrombin mediates platelet aggregation and subsequent
      thromboxane A2 formation during coronary thrombolysis.
AB  - We examined the effect of a specific thrombin inhibitor, Ro 46-6240, alone and
      combined with an antagonist of the platelet GP IIb/IIIa, Ro44-9883, on the
      response to tissue-type plasminogen activator in a canine model of thrombolysis.
      Platelet activity was determined by measuring the excretion of 2,3
      dinorthromboxane (TX)B2, an enzymatic metabolite of TXA2. Ro 46-6240 administered
      before tissue-type plasminogen activator induced a dose-dependent prolongation of
      the activated partial thromboplastin time and prothrombin time. The time to
      reperfusion decreased dose-dependently (P < .01) to 10 +/- 6 min vs. 52 +/- 5 min
      in controls. Ro 46-6240 also prevented reocclusion, which occurred in every case
      in control experiments. Urinary excretion of 2,3-dinor-TXB2 increased from 3 +/-
      1 to 37 +/- 9 ng/mg creatinine in controls after reperfusion. This increase was
      reduced in a dose-dependent fashion by Ro 46-6240, such that at the highest dose,
      urinary 2,3-dinor-TXB2 after reperfusion was 5.6 +/- 1 ng/mg creatinine. Similar
      functional and biochemical effects were seen when a subthreshold dose of Ro 46
      6240 was combined with Ro 44-9883. At the dose used, Ro 44-9883 alone abolished
      platelet aggregation ex vivo but failed to modify the response to tissue-type
      plasminogen activator or the excretion of 2,3-dinor-TXB2 after reperfusion (51 +/
      6 ng/mg creatinine, n = 3). However, the combination of Ro 44-9883 and Ro 46
      6240 reduced the time to reperfusion (40 +/- 8 vs. 68 +/- 15 min; n = 7, P <
      .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5
      +/- 1 ng/mg creatinine, n = 4). These findings suggest that thrombin mediates
      platelet activation during coronary thrombolysis. The increased platelet activity
      results in platelet aggregation and a subsequent increase in TXA2 formation.

PMID- 9190852
TI  - Stimulation of airway mucociliary transport and epithelial ciliary motility by
      the triazolopyridazin derivative TAK-225.
AB  - To elucidate whether a newly developed antiallergic drug, the triazolopyridazin
      derivative TAK-225, alters airway mucociliary clearance and, if so, what the
      mechanism of action is, we measured mucociliary transport in the rabbit tracheal
      mucosa ex vivo and ciliary motility of the tracheal epithelium in vitro.
      Mucociliary transport function was determined by the transport rate of Evans blue
      dye that had been placed on the mucosal surface above the carina. Oral
      administration of TAK-225 (0.3-30 mg/kg) increased Evans blue transport toward
      the larynx in a dose-dependent manner. Addition of TAK-225 caused a rapid and
      sustained increase in the ciliary beat frequency of tracheal epithelium, as
      assessed by photoelectric method; the maximal increase from the base-line value
      was 25.1 +/- 4.6% (P < .01), and the concentration required to produce a half
      maximal effect (EC50) was 3.1 +/- 0.8 x 10(-7) M. This effect was greatly
      attenuated by pretreatment with the cAMP antagonist adenosine 3',5'-cyclic
      monophosphorothioate, but not by Ca++-free medium containing ethylene glycol-bis
      [3-aminoethyl ether] N,N,N',N'-tetraacetic acid and [1,2
      bis(2)aminophenoxy]ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester.
      Incubation of tracheal epithelium with TAK-225 increased intracellular cAMP
      contents in a concentration-dependent manner. These results suggest that TAK-225
      enhances airway mucociliary clearance probably through cAMP-mediated stimulation
      of ciliary motility of airway epithelium.

PMID- 9190853
TI  - The stereo-isomers of the anticonvulsant ARL 12495AA limit sustained repetitive
      firing and modify action potential properties of rat hippocampal neurons in
      vitro.
AB  - The effects of the resolved enantiomers of the anticonvulsant ARL 12495AA ((S,R)
      1-methyl-1,2-diphenylethylamine-monohydrochloride), (S)-ARL 12495 and (R)-ARL
      12495, on (1) sustained repetitive firing and (2) action potential properties of
      rat hippocampal neurons were assessed. Whole-cell current-clamp recordings were
      made from CA1 neurons in slices of adult rat brain. Sustained repetitive firing
      was evoked by injection of long duration (500 msec) depolarizing (20-400 pA)
      current pulses. Sustained repetitive firing was inhibited by (S)-ARL 12495 and by
      (R)-ARL 12495; the threshold concentration was 5 microM reaching a near maximum
      at 400 microM. Comparing the potencies of the two isomers, IC50 values of 55 and
      39 microM were calculated for (S)-ARL 12495 and (R)-ARL 12495, respectively. The
      actions of the two drugs on neuronal firing were not therefore markedly
      stereoselective. Examination of individual spike properties revealed a
      concentration-related (12-400 microM) and time-dependent increase in the spike
      duration by (S)-ARL 12495 and (R)-ARL 12495. The spike amplitude and rate-of-rise
      were attenuated significantly by these two drugs. Both isomers decreased the
      after-hyperpolarization after a single spike and after trains of spikes. No clear
      stereoselectivity was demonstrable for the effects of the two enantiomers on
      action potential properties. Possible mechanisms of action for (S)-ARL 12495 and
      (R)-ARL 12495 including partial blockade of voltage-sensitive sodium channels and
      modulation of potassium channels are considered. The possibility that multiple
      mechanisms of action contribute to the therapeutic efficacy of the anticonvulsant
      ARL 12495AA is discussed.

PMID- 9190854
TI  - Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2
      hydroxylation: a study using microsomes obtained from putative extensive and poor
      metabolizers of S-mephenytoin and eleven recombinant human CYPs.
AB  - Cytochrome P450 (CYP) involved in the two major pathways of imipramine (IMI) was
      reappraised using human liver microsomes phenotyped for S-mephenytoin 4'
      hydroxylation in vitro and 11 recombinant human CYP isoforms. Individual Eadie
      Hoffstee plots for IMI N-demethylation and 2-hydroxylation showed a monophasic
      profile in microsomes obtained from three putative S-mephenytoin poor metabolizer
      (PM) livers, whereas the plots gave a biphasic relationship (except for one case
      in 2-hydroxylation) in those from the three extensive metabolizer (EM) livers.
      Effects of CYP-selective inhibitor/substrate probes on the two metabolic
      reactions were examined at the two IMI concentrations (2 and 400 microM) with
      microsomes obtained from the two PM and three EM livers. S-mephenytoin inhibited
      IMI N-demethylation by 50% at the low concentration in microsomes from the EM
      livers with no discernible effect on this pathway in those from the PM livers.
      Furafylline inhibited the N-demethylation by about 60% at the low and high
      substrate concentrations in microsomes from both the EM and PM livers. Quinidine
      abolished the 2-hydroxylation at the low and high concentrations in microsomes
      from both the EM and the PM livers. Among the recombinant human CYPs, CYP2C19,
      2C18, 2D6, 1A2, 3A4 and 2B6 in rank order catalyzed the N-demethylation, whereas
      CYP2D6, 2C19, 1A2, 2C18 and 3A4 catalyzed the 2-hydroxylation. The Km values
      obtained from recombinant CYP2C19 and 1A2 approximated those of the high- and low
      affinity components from human liver microsomes for IMI N-demethylation,
      respectively. For IMI 2-hydroxylation, the respective Km values obtained from
      recombinant CYP2D6 and 2C19 were close to those of the high- and low-affinity
      components from human liver microsomes. Our human liver microsomal study using
      the near-therapeutic IMI concentration (2 microM) suggests that 1) CYP2C19 and
      1A2 are involved in the N-demethylation and the 2-hydroxylation is mediated
      exclusively by CYP2D6 and partially by CYP2C19 in the EM livers, and 2) CYP1A2
      and 2D6 play a major role in IMI N-demethylation and 2-hydroxylation,
      respectively, in the PM livers. Our recombinant human CYP isoform study, in
      general, supports this conclusion.

PMID- 9190855
TI  - The passage of azidodeoxythymidine into and within the central nervous system:
      does it follow the parent compound, thymidine?
AB  - The transport of azidodeoxythymidine (AZT) into and within the central nervous
      system (CNS) has special clinical significance due to the ability of AZT to
      alleviate certain neurological symptoms associated with the acquired
      immunodeficiency syndrome (AIDS). AZT was thought to be similar to its parent
      compound, thymidine, in that it entered the CNS via the choroid plexuses (blood
      CSF barrier) and could not cross the blood-brain barrier (BBB). However, a
      saturable transport system for thymidine at the BBB has recently been identified.
      The aim of this study was to test the hypothesis that AZT follows its
      physiological counterpart in its mode of entry into and movement within the CNS.
      Initial experiments using the in situ brain perfusion technique indicated that
      the blood-to-CNS transfer constants for [3H]AZT (blood-to-cerebrum; 0.95 +/- 0.12
      microl/min/g) were significantly lower than those determined for [3H]thymidine.
      Also, [3H]AZT entered the CNS purely by a diffusive process. The movement of
      [3H]AZT within the CNS was further investigated by a ventriculocisternal
      perfusion technique and indicated that the majority of intraventricularly
      perfused [3H]AZT remained within the ventricles (79.9%), with little escaping to
      blood (14.1 +/- 3.1%) or brain (6.0 +/- 1.3%). Overall, these results suggest
      that the choroid plexus/CSF pathway was unlikely to be solely responsible for the
      levels of [3H]AZT observed in brain and that the BBB plays a significant role in
      the brain entry of this analog. However, in contrast to thymidine, AZT enters the
      CNS purely by a diffusional process.

PMID- 9190856
TI  - Spinal infusion of N-methyl-D-aspartate antagonist MK801 induces hypersensitivity
      to the spinal alpha-2 agonist ST91 in the rat.
AB  - MK801 (MK), an N-methyl-D-aspartate (NMDA) receptor antagonist, attenuates
      tolerance to spinal opioids. Whether this applies to other G-protein-coupled
      receptor systems is unknown. This study examines the effects of continuous spinal
      MK on tolerance to the antinociceptive effect of continuous spinal infusion of
      the alpha-2 agonist ST91 (ST). Intrathecal (i.t.) infusion pumps were implanted
      in rats which delivered for 7 days: saline (1 microl/h); ST (40 nmol/microl/h);
      MK (10 nmol/microl/h) + ST (40 nmol/microl/h); or MK (10 nmol/microl/h).
      Antinociception was measured daily on the hot plate. On day 8, groups received
      i.t. boluses of ST to generate dose-response curves. A separate ST-infused group
      received MK (10 nmol i.t.) on day 7. Each group received ST (40 nmol i.t.) 7 days
      after discontinuation of infusion. Co-infusion of MK with ST resulted in
      attenuation of the right shift in dose response seen in ST-infused rats and a
      small preservation of effect on daily testing. However, MK-infused rats showed a
      significant left shift in ST dose response. Acutely administered, MK did not
      restore ST sensitivity. One week after cessation of infusion, ST and ST + MK
      groups showed shorter duration of effect after i.t. ST bolus than controls. In
      conclusion, chronic spinal MK partially attenuates loss of sensitivity to chronic
      spinal ST. This supports the hypothesis that opioid- and adrenoceptor-induced
      tolerances are similarly modulated by the NMDA receptor. However, the increased
      sensitivity induced by MK alone suggests that NMDA receptor antagonism may not
      prevent the development of tolerance itself but may alter the expression of
      tolerance by inducing sensitivity via other alterations in cellular function.

PMID- 9190857
TI  - Multidrug resistance-reversing agents increase vinblastine distribution in normal
      tissues expressing the P-glycoprotein but do not enhance drug penetration in
      brain and testis.
AB  - The aim of this study was to assess whether P-glycoprotein (Pgp) inhibitors
      altered the blood-brain barrier and enhanced vinblastine (VBL) distribution in
      brain, testis and other Pgp-expressing tissues. Trifluoperazine, cyclosporin A,
      amiodarone, quinidine, the nifedipine analog Bay K8644 and verapamil were
      selected among Pgp inhibitors and were administered intraperitoneally 1 hr before
      an intravenous dose of 10 mg/kg VBL. Trifluoperazine and cyclosporin A were also
      administered intraperitoneally for 7 days before VBL. VBL and its metabolite O4
      deacetylvinblastine were measured in tissues by high-performance liquid
      chromatography assay. None of the reversing agents (RA) appreciably raised VBL
      concentrations in brain and testis, whereas all except quinidine significantly
      enhanced VBL distribution in liver and kidney; the most effective were
      trifluoroperazine and cyclosporin A. In mice treated with RA and VBL combined, O4
      deacetylvinblastine levels in liver and kidney reached either the same or higher
      levels than in mice treated with VBL alone, indicating that the increase in VBL
      levels is not due to inhibition of its metabolism. The main conclusions are that
      (1) inhibitors of Pgp, even at high doses, do not increase the permeability of
      the blood-brain barrier in mice, suggesting caution in the clinical use of RA
      combined with antitumor agents for brain tumors; and (2) several RA achieve high
      enough concentrations to enhance the distribution of VBL in other normal tissues
      expressing Pgp, thus potentially increasing VBL toxicity.

PMID- 9190858
TI  - CP-96,345, which inhibits [3H] substance P binding, selectively inhibits the
      behavioral response to intrathecally administered N-methyl-D-aspartate, but not
      substance P, in the mouse.
AB  - ((2S,3S)-[cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-az
      abicyclo[2.2.2]octan-3-amine]) (CP-96,345) noncompetitively inhibits substance P
      (SP) binding at the neurokinin-1 (NK-1) site and has been widely used to
      determine the extent of NK-1 activity in nociception. To test the selectivity of
      this compound in vivo regarding other putative nociceptive transmitters, such as
      excitatory amino acids, we compared the actions of CP-96,345 to those of ((2R,3R)
      [cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-az abicyclo[2.2.2]octan-3
      amine]), a less active isomer, on behavioral responses induced by SP, N-methyl-D
      aspartate (NMDA) and kainic acid (KA) injected intrathecally in mice. When
      injected intrathecally, SP, NMDA or KA produce a caudally directed biting and
      scratching behavior that lasted for approximately 60 to 90 sec. At a dose as high
      as 2 nmol, CP-96,345 had no effect on responses induced by a single injection of
      22.5 pmol of SP. In contrast, NMDA-induced behaviors were inhibited by CP-96,345
      in a dose-related fashion beginning at a dose as low as 0.02 nmol. There was also
      an inhibitory effect of CP-96,345 on KA-induced activity that was not dose
      related. The more potent inhibitor of [3H] SP binding, (+)-(2S,3S)-3-(2
      methoxybenzylamino)-2-phenylpiperidine (CP-99,994), was approximately 10 times
      more potent in inhibiting NMDA-induced activity than CP-96,345. CP-99,994 also
      inhibited NMDA-induced activity at doses that failed to inhibit SP-induced
      behavior. Also attenuated by CP-96,345 was the development of sensitization to
      the behavioral effects produced by repeated injections of KA and desensitization
      to repeated injections of SP, phenomena linked to an action of the N-terminus of
      SP. NMDA-induced behaviors and sensitization to KA were found to be sensitive to
      verapamil, consistent with their mediation by calcium. These results indicate
      that either CP-96,345 and CP-99,994 do not inhibit NK-1-induced activity in the
      mouse spinal cord, or that exogenously administered SP does not induce behavioral
      responses by an interaction with NK-1 receptors. Whether CP-96,345 acts by a
      mechanism that involves inhibition of calcium channels and/or SP N-terminal
      activity requires further testing.

PMID- 9190859
TI  - Pharmacodynamics of acute tolerance to multiple nicotinic effects in humans.
AB  - Tolerance is an important determinant of addiction as well as therapeutic and/or
      toxic effects of drugs. The development of acute tolerance to various effects of
      nicotine was studied in nine healthy smokers who were abstaining from tobacco.
      Nicotine was infused rapidly to reach a concentration of about 25 ng/ml, followed
      by a computer-controlled infusion to maintain that concentration. A novel
      semiparametric model of nicotine effects and tolerance was developed. Tolerance
      to various effects of nicotine (increases in heart rate, blood pressure, plasma
      epinephrine and energy expenditure) occurred within the range of nicotine levels
      found in smokers. However, the rate of tolerance development varied considerably.
      The half-lives of tolerance ranged from 3.5 min for the increase in energy
      expenditure to 70 min for systolic blood pressure. There was no apparent
      tolerance to the effects on free fatty acid concentrations, which reflects
      lipolysis. Differences in the pharmacodynamics of tolerance may reflect
      differences in rate of desensitization of various subtypes of nicotinic receptors
      and/or differences in mechanisms of tolerance for various nicotinic effects.

PMID- 9190860
TI  - Characterization of nifedipine block of the human heart delayed rectifier,
      hKv1.5.
AB  - Nifedipine antagonizes L-type Ca+ channels found throughout the cardiovascular
      system, but also blocks Kv channels, which are members of the same supergene
      family. We have examined nifedipine actions on the human heart K+ channel
      (hKv1.5) expressed in human embryonic kidney cells. Peak and steady-state
      currents on depolarization were reduced by nifedipine with Kd values of 18.6 +/-
      2.7 and 6.3 +/- 0.5 microM respectively at +40 mV, and with Hill coefficients of
      0.75 +/- 0.04 and 0.93 +/- 0.03. Block increased rapidly between -10 mV and +10
      mV, coincident with channel opening and suggested an open channel block
      mechanism, which was confirmed by tail current crossover on repolarization
      (unblock on channel closing). At more positive potentials than +20 mV, block was
      relieved. The time constants (tau2) for nifedipine block of hKv1.5 were
      concentration and voltage dependent. At +40 mV, tau2 was 16.7 +/- 0.8 (10
      microM), and 4.8 +/- 0.6 msec (50 microM), (n = 4-8). Using a first order kinetic
      analysis, apparent binding constants were 5.64 x 10(6) M(-1) s(-1) (k(+1), on
      rate) and 37.5 s(-1) (k(-1), off-rate), with a Kd of 6.65 microM, close to that
      obtained from the dose-response curve. An increase in the off-rate (k(-1)) could
      explain relief of block > +20 mV. The rank order of block under different patch
      configurations was whole-cell approximately = outside-out > inside-out >> cell
      attached macropatches. Together, these suggested a binding site for nifedipine at
      the extracellular pore of hKv1.5 or at a hydrophobic channel domain within the
      lipid bilayer at a site that is more accessible from the extracellular side.

PMID- 9190861
TI  - Regulation of [Ca++]i in human neuroblastoma (SH-SY5Y) cells expressing
      recombinant rat angiotensin1A receptors by angiotensin II and carbachol.
AB  - The ability of angiotensin II (AII) to regulate [Ca++]i in human neuroblastoma
      (SH-SY5Y) cells stably expressing recombinant rat AT1A receptors was investigated
      using microfluorimetric methods, and compared to responses obtained by
      stimulation of native muscarinic receptors. Applications of AII or carbachol
      produced biphasic rises of [Ca++]i, but in Ca++-free solutions (containing 1 mM
      ethylene glycol-bis (beta-aminoethyl ether)N,N,N,'N'-tetraacetic acid), both
      agonists produced only transient monophasic rises of [Ca++]i, and second
      applications were without effect. Application of Ca++(o) (2.5 mM) to cells after
      exposure to either agonist produced a Ni2+-sensitive rise of [Ca++]i in the
      absence of agonist ("capacitative Ca++ influx"). After removal of Ca++(o), both
      AII and carbachol elicited a second rise of [Ca++]i. Thapsigargin (1 microM)
      prevented these second rises of [Ca++]i. During capacitative Ca++ influx,
      application of AII failed to produce a further rise of [Ca++]i. In contrast,
      carbachol produced a further rise of [Ca++]i, attributable to activation of both
      nicotinic and muscarinic receptors, because it was reduced (but not abolished) by
      mecamylamine (1 microM) and was observed when muscarine was used as the agonist.
      Thus, activation of recombinant AT1A and muscarinic receptors in SH-SY5Y cells
      leads to mobilization of Ca++ from a common intracellular pool, and stimulates
      capacitative Ca++ influx. Muscarinic (but not AII) receptor occupancy is capable
      of stimulating an additional Ca++ influx pathway.

PMID- 9190862
TI  - Platelet-activating factor contributes to immune cell and oxidant-mediated
      intestinal secretion.
AB  - The sensitivity of the Ussing-chambered rat colon to stimulation of Cl- secretion
      (as measured by the change in short-circuit current) by exogenous platelet
      activating factor (PAF) was increased significantly by washing the colon in vitro
      with Ringer's solution containing fatty acid-free albumin. When the wash solution
      was extracted with chloroform/methanol and the lipid extract was added back to
      Ussing-chambered colons, inhibition of PAF-stimulated short-circuit current was
      observed, whereas short-circuit current responses to bradykinin or vasoactive
      intestinal peptide were not affected. Hypoxia appears to be an important trigger
      for the down-regulation of the PAF response. These data suggest that hypoxia
      releases PAF or an endogenous lipid PAF inhibitor that desensitizes PAF receptors
      on colonic epithelial or mucosal cells. The short-circuit current response of
      rabbit colon to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine was
      not inhibited by any PAF antagonist devoid of cyclooxygenase inhibitory activity
      but was strongly inhibited by indomethacin. In contrast, anti-IgE- or H2O2
      stimulated short-circuit current in rat colon was inhibited by specific PAF
      antagonists, and this inhibition was additive with indomethacin. Both anti-IgE
      and H2O2 significantly increased PAF production by rat colon. These data suggest
      that PAF plays an important role in oxidant (H2O2)- and anti-IgE-mediated colonic
      Cl- secretion but not in Cl- secretion mediated by formyl-methionyl-leucyl
      phenylalanine-stimulated phagocytes.

PMID- 9190863
TI  - Pharmacological characterization of the uroselective alpha-1 antagonist Rec
      15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity,
      part I.
AB  - Alpha adrenoceptor antagonists have been convincingly shown to be beneficial in
      reducing both subjective and objective indices of urethral obstruction in benign
      prostatic hyperplasia. Rec 15/2739 (SB 216469) is a novel alpha-1 adrenoceptor
      (alpha-1 AR) antagonist currently being developed for benign prostatic
      hyperplasia. When evaluated in radioligand binding assays with expressed animal
      or human alpha-1 ARs, Rec 15/2739 shows marked to moderate selectivity for the
      alpha-1a AR subtype. Its affinity for the recombinant alpha-2 AR subtypes or
      native dopaminergic D2 receptor was about 100-fold lower than that for alpha-1a
      AR subtype. In canine tissues, Rec 15/2739 was 20-fold more potent as an
      inhibitor of [3H]prazosin binding to prostate vis-a-vis aorta. Functional studies
      in isolated rabbit tissues also confirmed the uroselectivity of Rec 15/2739, with
      substantially higher affinity (Kb = 2-3 nM) being observed in urethra and
      prostate, compared with ear artery and aorta (Kb = 20-100 nM). The in vitro
      selectivity observed with Rec 15/2739 was confirmed in vivo in the anesthetized
      dog, comparing potency against norepinephrine- or hypogastric nerve stimulation
      induced urethral contraction with its ability to reduce diastolic blood pressure.
      In this model, Rec 15/2739 had greater selectivity than any other alpha-1 AR
      antagonist examined, including terazosin and tamsulosin. Based on the low potency
      of prazosin and some of its structural analogs in the rabbit and dog lower
      urinary tract tissues, it appears that norepinephrine contracts these tissues via
      activation of the alpha-1L AR. Hence this alpha-1 AR subtype, rather than the
      alpha-1A AR, may mediate the contraction in vivo.

PMID- 9190865
TI  - Neurokinin A-induced vasoconstriction and muscular contraction in the rat
      isolated stomach: mediation by distinct and unusual neurokinin2 receptors.
AB  - This study examined the pharmacological identity of the tachykinin receptors
      which in the rat stomach mediate vasoconstriction and muscular contraction. The
      vasculature of the rat isolated stomach was perfused with oxygenated Krebs buffer
      containing 3% dextran. Vasoconstrictor responses were recorded as increases in
      the vascular perfusion pressure and gastric contractions were measured as
      increases in the intraluminal pressure. By examining the effects of selective
      agonists and antagonists for tachykinin neurokinin (NK)1, NK2 and NK3 receptors
      it was found that the vasculature contained only NK2 receptors that were
      activated by the NK2 receptor agonist [betaAla8]-NKA-(4-10) and inhibited by the
      NK2 receptor antagonists MEN-10,627 and GR-94,800. However, the vasoconstrictor
      action of NKA was blocked only when the preparations were exposed to a
      combination of NK1, NK2 and NK3 receptor antagonists (SR-140,333, MEN-10,627, PD
      161,182). In contrast, the NKA-evoked contraction of the gastric musculature was
      suppressed by NK2 receptor antagonists but little affected by NK1 or NK3 receptor
      antagonists. This observation was consistent with the predominance of NK2
      receptors on the muscle as revealed by the effects of receptor-selective NK1, NK2
      and NK3 agonists and antagonists. These results demonstrate that the major
      tachykinin receptor type present on the gastric vasculature and musculature is a
      NK2 receptor that is sensitive to receptor-selective agonists and antagonists.
      The NKA-evoked gastric contraction is also primarily due to NK2 receptor
      activation, whereas the NKA-induced vasoconstriction is mediated by a distinct
      and unusual type of NK2-like receptor that is blocked by a combination of NK1,
      NK2 and NK3 receptor antagonists only.

PMID- 9190864
TI  - Pharmacological characterization of the uroselective alpha-1 antagonist Rec
      15/2739 (SB 216469): role of the alpha-1L adrenoceptor in tissue selectivity,
      part II.
AB  - The aim of the present work was to investigate whether or not the uroselectivity
      of Rec 15/2739 and several other alpha-1 adrenoceptor (alpha1-AR) antagonists
      observed in the anesthetized dog could be related to selectivity of these
      compounds for a particular alpha-1 AR subtype. The binding affinity of the tested
      compounds for canine prostate alpha-1 ARs and their in vitro functional affinity
      for the alpha-1 ARs of rabbit urethra and prostate correlated with their
      functional affinity for the alpha-1L AR subtype, but not with the binding
      affinity for recombinant animal and human alpha-1a, alpha-1b and alpha-1d AR
      subtypes. Similar results were obtained when the in vivo potency on urethral
      pressure was correlated with the affinity for the alpha-1 AR subtypes; also in
      this case alpha-1L AR gave the best correlation. No correlation was obtained by
      considering the other alpha-1 AR subtypes. The in vivo hypotensive effects
      observed in dog after i.v. administration of the considered compounds correlated
      only with the binding affinity for the animal and human alpha-1d subtype. In
      conclusion, the results shown in the present paper indicate that the potencies of
      different alpha-1 antagonists against the contractions induced by norepinephrine
      on tissues of the lower urinary tract of rabbits and dogs are better correlated
      with their affinity for the putative alpha-1L subtype than for the alpha-1a
      subtype. Only the compounds showing selectivity for the alpha-1L subtype versus
      the alpha-1d subtype proved highly selective in vivo for the lower urinary tract
      versus the vascular tissues.

PMID- 9190866
TI  - Nonpeptide tachykinin receptor antagonists: I. Pharmacological and
      pharmacokinetic characterization of SB 223412, a novel, potent and selective
      neurokinin-3 receptor antagonist.
AB  - The in vitro and in vivo pharmacological profile of SB 223412 [(S)-(-)-N-(alpha
      ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carbo xamide], a novel human NK-3 (hNK
      3) receptor antagonist, is described. SB 223412 demonstrated enantioselective
      affinity for inhibition of [125I][MePhe7]neurokinin B (NKB) binding to membranes
      of CHO cells expressing the hNK-3 receptor (CHO hNK-3). SB 223412, the (S)
      isomer, (Ki = 1.0 nM), has similar affinity as the natural ligand, NKB (Ki = 0.8
      nM) and another nonpeptide NK-3 receptor antagonist, SR 142801 (Ki = 1.2 nM). SB
      223412 was selective for hNK-3 receptors compared with hNK-1 (>10,000-fold
      selective) and hNK-2 receptors (>140-fold selective), and selectivity was further
      demonstrated by its lack of effect, in concentrations up to 1 or 10 microM, in
      >60 receptor, enzyme and ion channel assays. SB 223412 enantioselectively
      inhibited the NKB-induced Ca++ mobilization in HEK 293 cells stably expressing
      the hNK-3 receptor. SB 223412 (10-1,000 nM) produced concentration-dependent
      rightward shifts in NKB-induced Ca++ mobilization concentration-response curves
      with a Kb value of 3 nM. In addition, SB 223412 antagonized senktide-induced
      contraction in the isolated rabbit iris sphincter muscle (Kb = 1.6 nM). In mice,
      oral administration of SB 223412 produced dose-dependent inhibition of behavioral
      responses induced by the NK-3 receptor-selective agonist, senktide (ED50 = 12.2
      mg/kg). Pharmacokinetic evaluation of SB 223412 in rat and dog indicated low
      plasma clearance, oral bioavailability and high and sustained plasma
      concentrations after 4 to 8 mg/kg oral dosages. The preclinical profile of SB
      223412 (high affinity, selectivity, reversibility and oral activity) suggests
      that it will be a useful tool compound to define the physiological and
      pathophysiological roles of NK-3 receptors.

PMID- 9190867
TI  - Effect of cisapride and renzapride on gastrointestinal motility and plasma
      motilin concentration in dogs.
AB  - The effects of cisapride and renzapride (BRL 24924), on plasma concentration of
      motilin and gastroduodenal motility were studied in seven dogs with implanted
      force transducers in the antrum and duodenum. In the interdigestive state, the
      i.v. administration of cisapride (5 mg) or renzapride (5 mg) administered in
      phase I resulted in a prompt and marked increase in plasma motilin concentration
      and in gastroduodenal motility. Mean plasma motilin levels during the first 30
      min after cisapride and after renzapride injection were 85.0 +/- 6.5 (+/- S.E.)
      and 96.1 +/- 6.3 pM., respectively. These values were significantly greater (P <
      .001) than those for the corresponding time period of the control cycle, 52.2 +/-
      5.6 and 57.4 +/- 5.3 pM (mean phase III level, 120 +/- 8.1 pM), respectively. The
      increases in the motilin level after cisapride or renzapride coincided with
      significant increases in contractile activities of the antrum to 43.2 +/- 5.3%
      and 44.9 +/- 4.6% and of the duodenum to 28.4 +/- 3.1% and 34.2 +/- 2.2% of phase
      III activity (100%) from that in the corresponding control period, 0.7 +/- 0.4%
      and 0.2 +/- 0.1%, respectively. The changes in both plasma motilin and motility
      in response to the two drugs were abolished completely by the i.v. administration
      of atropine. The drugs also enhanced the meal-induced contractile activities of
      the antrum as well as the duodenum but failed to influence the postprandial
      plasma motilin concentration. We conclude that cisapride and renzapride have
      similar effects on plasma motilin and gastroduodenal motility: 1) the two drugs
      increase plasma motilin levels and stimulate gastroduodenal motility in the
      interdigestive state, and 2) in the digestive state, both drugs enhance motility
      without influencing the plasma motilin levels.

PMID- 9190868
TI  - Alprazolam in young and elderly men: sensitivity and tolerance to psychomotor,
      sedative and memory effects.
AB  - This study was designed to determine whether age influences sensitivity to
      alprazolam and/or rate of acute tolerance development to the effects of
      alprazolam. Three treatments were each separated by 4 weeks. Twenty-five young
      (ages 22-35) and 13 elderly (ages 65-75) men received 2 mg of alprazolam/2 min
      i.v. Blood samples were obtained over 48 hr, and sedative, psychomotor and memory
      effects were assessed serially for 12 hr. Clearance was lower (P = .05) and
      elimination t[1/2] was longer (P = .005) in the elderly, but area under the
      concentration curve to 12 hr and maximum concentration did not differ by age
      group. Maximum impairment was greater in the elderly for all assessments. Mean
      EC50 values differed between the elderly (25.3 and 25.0 ng/ml) and the young
      (39.8 and 36.5 ng/ml) on card sorting and digit symbol substitution, respectively
      (P < .001). Bolus treatment data were used to individualize doses for the
      crossover of placebo and alprazolam; infusions were designed to maintain a
      plateau alprazolam concentration between 1 and 9 hr. Alprazolam concentrations
      through 12 hr did not differ between the young and elderly. Median t[1/2] for
      offset of effect for digit symbol substitution was 2.8 hr in the young and 4.9 hr
      in the elderly (P = .05). Therefore, aging decreases alprazolam clearance and
      increases sensitivity to effects of alprazolam through a mechanism other than
      pharmacokinetics; aging also decreases the rate of offset of effect of
      alprazolam. In addition, the data provide insight into the intensity of initial
      effect as a determinant of rate of tolerance development.

PMID- 9190869
TI  - Enhancement of amphetamine- and cocaine-induced locomotor activity after chronic
      ethanol administration.
AB  - The effects of amphetamine and cocaine on locomotor activity in mice were studied
      after 3 weeks of chronic administration of ethanol by liquid diet. When testing
      was started 24 h after cessation of the ethanol treatment, no differences were
      seen on the first administration between the effects of the psychostimulants in
      controls and ethanol-treated animals, but after subsequent daily injections of
      amphetamine and cocaine, at doses that were insufficient to cause sensitization
      in controls, sensitization to both of these drugs was seen in ethanol-treated
      mice. When testing was started on the sixth day after cessation of the ethanol
      treatment, the effects of amphetamine on the first administration were
      significantly greater in ethanol-treated animals than in controls. After
      subsequent repeated daily injections, the locomotor stimulant effects of cocaine
      were greater in ethanol-treated mice than in controls. Administration of
      amphetamine for the first time 2 months after cessation of ethanol treatment also
      had a greater stimulant effect, compared with that in control animals. Two months
      after cessation of ethanol treatment, the first dose of cocaine caused a
      locomotor stimulation that was not seen in control animals, but sensitization was
      not seen after repeated cocaine administration in either group of animals. No
      differences in the effects of amphetamine or cocaine were seen after only 7 days
      of ethanol treatment. The results indicate that changes are still present in the
      CNS long after ethanol withdrawal hyperexcitability has subsided and that these
      changes result in increases in the effects of amphetamine and cocaine. Analysis
      of brain concentrations of the two psychostimulants suggested that metabolic
      changes were not responsible for the differing effects in control and ethanol
      treated animals. It is possible that alterations in mesolimbic dopamine
      transmission are responsible for the effects of the ethanol treatment.

PMID- 9190870
TI  - Acute effects of nitric oxide and cyclic GMP on human myocardial contractility.
AB  - Evidence that the activity of nitric oxide synthase and the generation of nitric
      oxide (NO) within the myocardium are enhanced in several cardiovascular disorders
      is increasing. Findings whether NO exerts a direct effect on cardiac
      contractility are contradictory. Therefore, the direct effect of the NO donor
      sodium nitroprusside (SNP) on isometric force of contraction of human atrial and
      ventricular myocardium was investigated, and the question was addressed whether
      the effects of NO on cardiac contractility are mediated via cGMP. Experiments
      were performed on isolated electrically driven (1 Hz, 37 degrees C) human right
      atrial trabecula and left ventricular papillary muscle preparations from
      nonfailing and terminally failing hearts. SNP led to a concentration-dependent
      decrease of force of contraction (FOC) with a maximum effect at 100 micromol/l.
      In atrial trabecula, SNP (100 micromol/l) caused an acute decrease in basal FOC
      as well as in FOC after application of isoprenaline or IBMX by 12.5 +/- 5% (P <
      .05), 16.6 +/- 3.7% (P < .05) and 18.3 +/- 4.2% (P < .05), respectively. The
      negative inotropic effects could be attenuated by the guanylyl cyclase inhibitor
      methylene blue. In papillary muscle preparations, NO release caused a maximum
      decrease in basal and in isoprenaline-enhanced FOC of 11.0 +/- 1.9% (P < .05) and
      23.6 +/- 1.5% (P < .05), respectively. In the presence of isoprenaline, the
      reduction of FOC was less pronounced in failing than in nonfailing papillary
      muscles. 8-bromo-cGMP caused a 38.2 +/- 5.2% decrease in atrial trabecula
      contractility. Both SNP and 8-bromo-cGMP caused a shortening of the contractile
      twitch with a premature onset of relaxation. As determined by radioimmunoassay,
      exposure of atrial trabecula to SNP (100 micromol) led to a 6-fold increase in
      myocardial cGMP concentrations, which could be attenuated by methylene blue. In
      conclusion, NO exerts a negative inotropic effect on human atrial and ventricular
      myocardium which seems to be mediated via generation of cGMP. The release of NO
      within the myocardium in a variety of cardiovascular disorders might explain
      decreases in cardiac contractility. The control of NO release could be an
      important target for future therapeutical interventions in these pathological
      conditions.

PMID- 9190871
TI  - Differential effects of naltrindole on morphine-induced tolerance and physical
      dependence in rats.
AB  - This study investigated the effect of delta opioid receptor blockade by
      naltrindole on the development of physical dependence and tolerance to the
      antinociceptive and respiratory depressive effects of morphine in rats. Chronic
      morphine was delivered either by s.c. injection of increasing amounts of morphine
      over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated
      with saline or naltrindole. Antinociception and respiratory depression were
      assessed after administration of a challenge dose of morphine, and withdrawal
      signs were determined after naloxone challenge. Naltrindole significantly
      attenuated the development of antinociceptive tolerance after all three chronic
      treatment regimens. In addition, rats pretreated with naltrindole displayed
      significantly fewer withdrawal symptoms and less weight loss after a naloxone
      challenge. In contrast, naltrindole did not prevent the development of tolerance
      to morphine-induced respiratory depression. These results imply that tolerance to
      antinociception and physical dependence involves adaptations at interacting mu
      and delta receptor populations, whereas tolerance to respiratory depression
      reflects actions of independent mu and delta receptor populations. These findings
      suggest that delta antagonists may have potential clinical application for
      decreasing the rapid development of tolerance to opiate-induced analgesia, while
      allowing for the development of protective tolerance to respiratory depression.

PMID- 9190872
TI  - Effects of drugs on response duration differentiation. V: differential effects
      under temporal response differentiation schedules.
AB  - The effects of methamphetamine, phencyclidine and delta9-tetrahydrocannabinol on
      responding under temporal response differentiation schedules were studied under
      three different time requirements. Under the schedules studied, Sprague-Dawley
      rats were required to make a continuous response for at least a minimum time
      duration, but not more than a maximum. Baseline performance under a temporal
      differentiation schedule usually produces a normal frequency distribution of
      response durations with the peak at or near the minimum duration required for
      delivery of the reinforcer. These frequencies were summed to calculate cumulative
      frequencies that were plotted as sigmoidal curves. Under the temporal
      differentiation 1-1.3 sec schedule, methamphetamine increased the frequency of
      short response durations at low doses, whereas high doses produced both long and
      short response durations, flattening the relative frequency distribution. Under
      the temporal differentiation 4-5.2 sec and 10-13 sec schedules, methamphetamine
      produced only short response durations, which shifted the relative frequency and
      cumulative frequency distribution of response durations leftward. delta9
      Tetrahydrocannabinol had little effect under the temporal differentiation 1-1.3
      sec and 4-5.2 sec schedules, but it greatly increased the relative frequency of
      short response durations under the 10-13 sec schedule. Phencyclidine produced a
      similar effect under all temporal differentiation schedules, increasing the
      relative frequency of short response durations. Thus the effect of drugs on
      timing behavior under these temporal differentiation schedules not only depended
      on the drug, but also depended on the dose and the time parameters of the
      schedule. These data suggest that drugs produce multiple effects on timing
      behaviors that depend on complex interactions among several factors.

PMID- 9190873
TI  - Effects of drugs on response duration differentiation. VI: differential effects
      under differential reinforcement of low rates of responding schedules.
AB  - The effects of methamphetamine, phencyclidine and delta9-tetrahydrocannabinol on
      responding under differential reinforcement of low rate schedules (DRL schedules)
      were studied under three different DRL time requirements. Under the DRL schedules
      studied, rats were required to space responses at least a minimum, but not more
      than a maximum, time interval apart. The time intervals between responses
      (interresponse times, or IRTs), when plotted as a frequency distribution, were
      usually a normal distribution with the peak at or near the minimum IRT required
      for delivery of the reinforcer. Methamphetamine flattened the IRT distribution
      and increased the frequency of long pauses under the DRL 1-1.3 sec schedule, but
      shifted the IRT distribution toward shorter IRTs under the DRL 4-5.2 and 10-13
      sec schedules. Under the DRL 1-1.3 sec schedule, phencyclidine also increased
      long pauses. Under the DRL 4-5.2 sec and 10-13 sec schedules, phencyclidine
      produced dual effects on the IRT relative frequency distributions producing
      increases in the proportion of short IRTs similar to methamphetamine at low
      doses, but higher doses increased long pauses as well. delta9
      Tetrahydrocannabinol had little effect on responding under the DRL 1-1.3 sec and
      DRL 4-5.2 sec schedules, but it greatly increased the relative frequency of short
      IRTs under the DRL 10-13 sec schedule. Thus the effects of drugs on responding
      under these DRL schedules depended on the drug, the dose and the time
      requirements of the schedule, which suggests that a simple description of the
      effects of drugs on timing behavior or time perception is inadequate.

PMID- 9190874
TI  - Effects of intrathecal or intracerebroventricular administration of nonsteroidal
      anti-inflammatory drugs on a C-fiber reflex in rats.
AB  - A C-fiber reflex elicited by electrical stimulation within the territory of the
      sural nerve was recorded from the ipsilateral biceps femoris muscle in
      anesthetized rats. The temporal evolution of the response was studied using a
      constant stimulus intensity (3 times threshold), and recruitment curves were
      built by varying the stimulus intensity from 0 to 7 times threshold. The
      intrathecal (i.t.) but not i.c.v. administration of aspirin, indomethacin,
      ketoprofen and lysine clonixinate resulted in dose-dependent depressions of the C
      fiber reflex. In contrast, saline was ineffective. Regardless of the route of
      administration, the drugs never produced disturbances in heart rate and/or acid
      base equilibrium. When a constant level of stimulation was used, 500 microg of
      aspirin i.t. induced a blockade of the reflex immediately after the injection,
      followed by a partial recovery. Indomethacin produced a stable depression, which
      reached 80 to 90% with an i.t. dose of 500 microg. Ketoprofen and lysine
      clonixinate produced a more stable effect; the highest doses (500 microg)
      produced a steady-state depression of approximately 50% for approximately 30 min.
      When the recruitment curves were built with a range of nociceptive stimulus
      intensities, all of the drugs except for indomethacin produced a dose-dependent
      decrease in the slopes and the areas under the recruitment curves without major
      modifications in the thresholds; indomethacin also induced a significant dose
      related increase in the threshold. The orders of potency for both stimulation
      paradigms with the i.t. route were the same, namely aspirin > indomethacin >
      lysine clonixinate > or = ketoprofen. It is concluded that nonsteroidal anti
      inflammatory drugs elicit significant antinociceptive effects at a spinal level,
      which do not depend on the existence of a hyperalgesic or inflammatory state.
      Such effects were not seen after injections within the lateral ventricle.

PMID- 9190875
TI  - Glucocorticoids and behavioral effects of psychostimulants. I: locomotor response
      to cocaine depends on basal levels of glucocorticoids.
AB  - In this study, we explored the influence of corticosterone, the major
      glucocorticoid in the rat, on the locomotor response to cocaine. In particular,
      in a first series of experiments, we determined the effects of suppressing
      endogenous glucocorticoids by adrenalectomy on a full dose-response curve of
      cocaine-induced locomotion and the influence, on this behavioral response, of
      different corticosterone concentrations, by implanting different corticosterone
      pellets in adrenalectomized rats. Adrenalectomy decreased the locomotor response
      to cocaine, inducing a vertical shift in the dose-response curve, and
      corticosterone dose-dependently reversed the decrease induced by adrenalectomy.
      The effects of adrenalectomy were fully replicated by the acute central infusion
      of corticosteroid receptor antagonists, and the action of glucocorticoids did not
      seem to depend on nonspecific effects such as a general alteration of motor
      responses or drug metabolism. Thus, neither adrenalectomy, corticosterone
      receptor antagonists nor corticosterone replacement modified saline-induced
      locomotion and the administration of corticosterone did not increase locomotion.
      Furthermore, adrenalectomy slightly increased brain concentrations of cocaine, an
      effect that cannot account for the decrease in drug-induced locomotion it
      induced. In a second series of experiments, we tested whether corticosterone
      levels at the time of adrenalectomy could influence the outcome of this surgical
      procedure on the locomotor response to cocaine. We thus adrenalectomized rats
      under different conditions resulting in different levels of the hormone.
      Corticosterone levels at the moment of adrenalectomy had dose-dependent long-term
      facilitatory effects on the response to the drug. These findings underline a
      facilitatory role of glucocorticoids in the behavioral effects of psychostimulant
      drugs.

PMID- 9190876
TI  - Glucocorticoids and behavioral effects of psychostimulants. II: cocaine
      intravenous self-administration and reinstatement depend on glucocorticoid
      levels.
AB  - Observations suggest that corticosterone, the principal glucocorticoid hormone in
      the rat, can modulate the behavioral effects of drugs of abuse. In this report,
      the influence of corticosterone on intravenous self-administration of cocaine was
      studied. In the first experiment, cocaine intravenous self-administration in
      adrenalectomized rats and in adrenalectomized rats receiving corticosterone
      replacement treatments was studied as a function of corticosterone concentrations
      and as a function of cocaine doses (0.025, 0.05, 0.1, 0.2, 0.4, 0.8
      mg/kg/infusion). In a second experiment, we tested, in intact rats, the effect of
      different doses of corticosterone (0.09, 0.18, 0.37, 0.58, 0.75 mg/kg) on the
      reinstatement of an extinguished cocaine self-administration behavior. It is
      reported that adrenalectomy markedly shifts the cocaine self-administration dose
      effect curve downward. This effect was dose-dependently reversed by
      corticosterone; a complete restoration being obtained for corticosterone levels
      in the range of those induced by stress. Corticosterone administration also
      precipitated dose-dependently the reinstatement of cocaine self-administration.
      The maximal effect was obtained for a dose of corticosterone producing an
      increase in plasma levels similar to the increase produced by an intense stress.
      In conclusion, our results show that glucocorticoids facilitate the reinforcing
      effects of cocaine and support the hypothesis that glucocorticoids are one of the
      biological factors determining vulnerability to substance abuse.

PMID- 9190877
TI  - Functional activation of cerebral blood flow abolished by scopolamine is reversed
      by cognitive enhancers associated with cholinesterase inhibition: a positron
      emission tomography study in unanesthetized monkeys.
AB  - The effects of somatosensory stimulation on the regional cerebral blood flow
      (rCBF) response were studied in unanesthetized monkeys before and after treatment
      with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine)
      that inhibit cholinesterase, using 15O-labeled water and high-resolution positron
      emission tomography. Under control conditions, somatosensory stimulation induced
      a significant increase in the rCBF response in the contralateral somatosensory
      cortex of monkey brain. Intravenous administration of scopolamine (50 microg/kg)
      resulted in abolishment of the rCBF response to stimulation. The rCBF response
      abolished by pretreatment with scopolamine was recovered by administration of
      physostigmine (1 or 10 microg/kg), E2020 (10 or 100 microg/kg) or tacrine (100 or
      1000 microg/kg), in a dose-dependent manner. The effect of E2020 (100 microg/kg)
      on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and
      tacrine were of shorter duration. These findings suggest that these compounds
      reversed the scopolamine-abolished rCBF response to somatosensory stimulation via
      enhancement of cholinergic neurotransmission, which was mainly induced by
      cholinesterase inhibition.

PMID- 9190878
TI  - Characterization of stably transfected kidney epithelial cell line expressing rat
      H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta
      lactam antibiotics.
AB  - We established stably transfected LLC-PK1 cells expressing the rat H+/peptide
      cotransporter PEPT1 (designated LLC-rPEPT1) and examined membrane localization
      and uptake by rat PEPT1 of oral beta-lactam antibiotics. The LLC-rPEPT1 cells
      expressed a novel PEPT1 protein with an apparent molecular mass of 75 kdaltons,
      which was found in rat intestinal membranes. The cell surface biotinylation of
      LLC-rPEPT1 cell monolayers grown on membrane filters showed that PEPT1 was
      localized predominantly on the apical membranes and, to a lesser extent, on the
      basolateral membranes. The amount of [14C]glycylsarcosine uptake in LLC-rPEPT1
      cell monolayers was 3-fold greater from the apical, than from the basolateral
      side, which suggested that rat PEPT1 expressed on both membranes was functionally
      active. LLC-rPEPT1 cells grown on plastic dishes transported differently charged
      oral cephalosporins such as ceftibuten (divalent anion lacking an alpha-amino
      group) and cephradine (zwitterion with an alpha-amino group) in the presence of
      an inward H+ gradient, whereas those transfected with the vector alone did not
      have transport activity. Kinetic analysis revealed that the LLC-rPEPT1 cells had
      much higher affinity for ceftibuten than for cephradine. Di- and tripeptides and
      bestatin, a dipeptide-like antineoplastic drug, potently inhibited the uptake of
      these cephalosporins. These results suggest that the LLC-rPEPT1 cells serve as a
      useful model with which to analyze the mechanisms involved in membrane targeting
      and substrate recognition by rat PEPT1.

PMID- 9190879
TI  - Immunochemical assay for recognition of 2-S-glutathionyl acetate, a glutathione
      conjugate derived from 1,1-dichloroethylene-epoxide.
AB  - Cytotoxicities induced by 1,1-dichloroethylene (DCE) are ascribed to cytochrome
      P450-dependent metabolism to an epoxide. Conjugation of the DCE-epoxide with
      glutathione (GSH) results in the formation of the conjugates 2-S-glutathionyl
      acetate (GTA) and 2-(S-glutathionyl) acetyl glutathione (GAG); GAG undergoes
      hydrolysis to form GTA, and thus GTA is a major metabolite of DCE metabolism. Our
      objective is to develop an antiserum against the chemically synthesized GTA, and
      for immunization, we have used a hapten that consists of GTA conjugated to bovine
      serum albumin (BSA) as the carrier protein and glutaraldehyde (GLUT) as a
      chemical cross-linker. The antisera were raised in rabbits and were characterized
      by using the following synthesized structural analogs: GTA, glycine-GLUT-BSA (GLY
      GLUT-BSA), GTA-GLUT-ovalbumin (GTA-GLUT-OVB), GTA-1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide-BSA (GTA-EDC-BSA), TRIS-GLUT-BSA, glutathione
      GLUT-BSA (GSH-GLUT-BSA). The enzyme-linked immunosorbent assay (ELISA) and slot
      immunoblotting were used to characterize the specificity of the antisera.
      Noncompetitive ELISA experiments showed that the reaction of the antiserum with
      the antigen was concentration-dependent. In the competitive ELISA, GTA-GLUT-BSA
      inhibited binding efficiently; in contrast, the unconjugated GTA did not inhibit
      binding to the antigen. Competitive studies with the other analogs indicated low
      or minimal reactivities with the antibodies, which were blocked by incubation
      with GLY-GLUT-BSA. However, there was residual reactivity with the antigen that
      was not competitively inhibited by either the GTA-EDC-BSA or the GSH-GLUT-BSA
      conjugates. Slot-blotting experiments confirmed the findings of the ELISA studies
      and revealed high specificity of the antiserum to detect the hapten. These
      results demonstrated the successful development of polyclonal antibodies to
      detect GTA and hence DCE-epoxide.

PMID- 9190880
TI  - In vivo characterization of sustained-release formulations of human growth
      hormone.
AB  - Long-acting formulations of recombinant human growth hormone (rhGH) were prepared
      by stabilizing and encapsulating the protein into three different injectable,
      biodegradable microsphere formulations composed of polymers of lactic and
      glycolic acid. The formulations were compared in juvenile rhesus monkeys by
      measuring the serum levels of rhGH and two proteins induced by hGH, insulin-like
      growth factor-I and IGF binding protein-3 (IGFBP-3) after single s.c.
      administration. All three formulations, which differed principally in the
      composition of the polymer, provided sustained elevated levels of all three
      proteins for several weeks, and the rate of release of rhGH differed among the
      formulations consistent with the molecular weight of the polymer used. All three
      formulations induced a higher level of insulin-like growth factor-I and insulin
      like growth factor binding protein than was induced by daily injections of the
      same amount of rhGH in solution. After three monthly injections of one of the
      formulations, both the rhGH and IGF-I levels remained elevated for nearly 90
      days. Immunogenicity of the rhGH released from this formulation, as assessed by
      the incidence of seroconversion to hGH and the titer of anti-hGH antibody in both
      the rhesus monkeys and transgenic mice expressing rhGH, was no greater than that
      of the unencapsulated protein. In addition, the microsphere injection sites
      appeared normal by macroscopic evaluation between 1 to 2 mo after microsphere
      administration and by microscopic evaluation between 2 to 3 mo. These results
      show that serum levels of a therapeutic protein can be sustained for an extended
      period when encapsulated into different formulations of injectable, biodegradable
      microspheres.

PMID- 9190881
TI  - Phosphate excretion and phosphate transporter messenger RNA in uremic rats
      treated with phosphonoformic acid.
AB  - The prevention of phosphate retention in chronic renal disease may reduce both
      renal osteodystrophy and disease progression. We evaluated the expression of the
      sodium-dependent phosphate transporter, NaPi-2, and the response to
      phosphonoformic acid (PFA) in rats with 5/6 nephrectomy-induced renal failure.
      Partial nephrectomy resulted in a significant proteinuria and reduced renal
      function. In addition, there was an approximately 50% reduction in the expression
      of NaPi-2 mRNA. Treatment of rats for 48 hr with PFA (0.6% in glucose drinking
      fluid) had no effect on NaPi-2 mRNA; however, PFA resulted in a significant
      increase in fractional phosphate excretion in both normal (7 +/- 0.5% vs. 3 +/-
      0.2%) and uremic (60 +/- 4% vs. 36 +/- 4%) rats. Plasma phosphate concentration
      was higher in uremic rats (2.5 +/- 0.1 mM) compared with normal rats (1.9 +/-
      0.04 mM) but not in uremic rats treated with PFA (2.1 +/- 0.04 mM). These data
      suggest that PFA can increase renal phosphate excretion independent of changes in
      phosphate transporter expression and prevent phosphate retention.

PMID- 9190883
TI  - Effects of rebamipide in a model of experimental diabetes and on the synthesis of
      transforming growth factor-beta and fibronectin, and lipid peroxidation induced
      by high glucose in cultured mesangial cells.
AB  - Oxidative stress has been proposed as the basis for the pathogenesis of diabetic
      nephropathy. Rebamipide is a novel antiulcer drug that has, in addition, oxygen
      radical scavenging activity. Our study examines whether rebamipide could
      ameliorate the pathophysiology associated with experimental diabetes in vivo,
      such as microalbuminuria, and to reverse the increased production of transforming
      growth factor-beta1 and fibronectin in SV-40 transformed murine mesangial cells
      in culture that were stimulated with high glucose. Chronic administration of
      rebamipide (100 mg/kg/day, p.o., for 3 wk) to rats, in which diabetes was
      previously induced by the i.v. injection of streptozotocin 50 mg/kg, reversed
      hyperglycemia, which would contribute to prevent the increases in urinary
      excretion rates of albumin and lipid peroxides observed in this experimental
      model. Rebamipide, at this dose level, did not cause any discernible effect on
      age-matched control rats. Rebamipide 2 mM was as effective as 20 mM of
      dimethylthiourea, a known hydroxyl radical scavenger, in inhibiting the increase
      in lipid peroxides, transforming growth factor-beta1, fibronectin mRNAs and
      proteins induced by incubation of cultured mesangial cells with high glucose. Our
      data suggest that rebamipide attenuates high glucose-induced nephropathy, which
      is attributable, in part, to its antioxidative property and, in part, to its
      effect on reversing hyperglycemia.

PMID- 9190882
TI  - Inhibition of growth factor-mediated tyrosine phosphorylation in vascular smooth
      muscle by PD 089828, a new synthetic protein tyrosine kinase inhibitor.
AB  - PD 089828, a novel protein tyrosine kinase inhibitor of a new structural class,
      the 6-aryl-pyrido-[2,3-d]pyrimidines, was identified by screening a compound
      library with assays that measured protein tyrosine kinase activity. PD 089828 was
      found to inhibit human full-length fibroblast growth factor (FGF) receptor-1
      (FGFR-1), platelet-derived growth factor (PDGF) receptor beta subunit (PDGFR
      beta), Src nonreceptor tyrosine kinase (c-Src) and epidermal growth factor (EGF)
      receptor (EGFR) tyrosine kinases with half-maximal inhibitory potencies (IC50
      values) of 0.15 +/- 0.02 (n = 4), 0.18 +/- 0.04 (n = 3), 1.76 +/- 0.28 (n = 4)
      and 5.47 +/- 0.78 (n = 6) microM, respectively. PD 089828 was further
      characterized as an ATP competitive inhibitor of the growth factor receptor
      tyrosine kinases (FGFR-1, PDGFR-beta and EGFR) but a noncompetitive inhibitor of
      c-Src tyrosine kinase with respect to ATP. In addition, PD 089828 inhibited PDGF-
      and EGF-stimulated receptor autophosphorylation in vascular SMC (VSMC) and basic
      FGF-mediated tyrosine phosphorylation in A121 cells with IC50 values similar to
      the potencies observed for inhibition of receptor tyrosine kinase activity. The
      inhibition of PDGF receptor autophosphorylation in VSMC by PD 089828 occurred
      rapidly, with maximal effects reached within 5 min of drug exposure. Inhibition
      after single exposure was long lasting but also rapidly reversible, occurring
      within 5 min after drug removal. The PDGF-induced association of downstream
      signaling proteins, including phosphoinositide-3-kinase (PI-3K), growth factor
      receptor binding protein-2 (GRB2), SH-2 domain and collagen like (Shc) and
      phospholipase Cgamma (PLCgamma), with VSMC PDGF receptors was also blocked as a
      result of the inhibition of PDGF-stimulated receptor autophosphorylation by PD
      089828. PD 089828 also inhibited the PDGF-induced tyrosine phosphorylation of the
      44- and 42-kDa mitogen-activated protein kinase isoforms. Moreover, the effects
      of PD 089828 were demonstrated in functional assays in which PDGF-stimulated DNA
      synthesis, PDGF-directed migration and serum-stimulated growth of VSMC were all
      inhibited to the same extent as PDGF receptor autophosphorylation (IC50 = 0.8,
      4.5 and 1.8 microM, respectively). These results highlight the biological
      characteristics of PD 089828 as a novel, broadly active protein tyrosine kinase
      inhibitor with long-lasting but reversible cellular effects. The potential
      therapeutic use of these broadly acting, nonselective inhibitors as
      antiproliferative and antimigratory agents could extend to such diseases as
      cancer, atherosclerosis and restenosis in which redundancies in growth-signaling
      pathways are known to exist.

PMID- 9190884
TI  - Involvement of nitric oxide in nicotinic receptor-mediated myopathy.
AB  - Previous studies have shown that nicotinic cholinergic agonists induce muscle
      cell degeneration. Although an involvement of calcium is well documented,
      subsequent intracellular steps have not been identified. The present experiments
      test whether nitric oxide (NO) may play such a role. Both the irreversible nitric
      oxide synthase inhibitor L-5N-iminoethyl ornithine and L-nitroarginine methyl
      ester, a reversible inhibitor, protected the muscle cells from the myopathic
      effects of nicotine. These results may suggest that nicotinic receptor
      stimulation produces an increase in NO that results in muscle cell degeneration.
      In line with this interpretation, exposure of the muscle cultures to the NO donor
      sodium nitroprusside resulted in a dose-dependent decline in myotube branch
      points. Neither L-5N-iminoethyl ornithine nor nitroprusside altered the binding
      of the nicotinic receptor agonist 125I-alpha-bungarotoxin to muscle cells in
      culture, which indicates that the effect of these agents was not mediated through
      an interaction at the nicotinic receptor recognition site. The results with
      agents that inhibit guanylate cyclase or modify extracellular levels of cGMP
      suggest an involvement of this cyclic nucleotide in the nicotinic receptor
      mediated myopathy. To conclude, the present results suggest that nicotinic
      receptor activation causes skeletal muscle degeneration through an increase in NO
      production and a possible involvement of cGMP.

PMID- 9190885
TI  - Effects of preconditioning with ebselen on glutathione metabolism and stress
      protein expression.
AB  - Selenium induces several proteins, including glutathione and stress proteins.
      These proteins have been shown to be cardioprotective against oxidative injury.
      To determine whether ebselen, a seleno-organic compound, can also induce these
      proteins and exert cardioprotective action, we examined the effects of
      preconditioning with ebselen on glutathione metabolism and stress protein
      expression and on myocyte injury induced by oxidative stress. Treatment of
      cultured cardiac myocytes with ebselen (0.3-30 microM) for 24 hr increased the
      reduced glutathione content. Glutathione reductase activity, but not glutathione
      peroxidase activity, was significantly elevated in a dose-dependent manner.
      Pretreatment with ebselen increased the expression of such stress proteins as
      heat shock protein 70 and heme oxygenase-1 (heat shock protein 32) in cardiac
      myocytes, as assessed by Western blotting. Expression of heat shock protein 70
      was increased only at a higher dose of ebselen (30 microM), whereas expression of
      heme oxygenase-1 was markedly increased at a lower dose of ebselen (3 microM).
      Under these conditions, the myocyte injury induced by hydrogen peroxide or
      simulated ischemia/reperfusion, assessed by the release of lactate dehydrogenase
      into the culture medium, was reduced by ebselen pretreatment in a dose-dependent
      manner. Results indicated that cardiac myocytes pharmacologically preconditioned
      with ebselen for 24 hr exhibited resistance to oxidative injury, possibly via the
      up-regulation of glutathione metabolism and the expression of stress proteins.

PMID- 9190886
TI  - Changes in the association of G protein subunits with the cloned mouse delta
      opioid receptor on agonist stimulation.
AB  - G proteins couple delta opioid receptors to multiple cellular effector systems
      and are critical components of the delta opioid signal transduction cascade. To
      investigate the physical association of delta opioid receptors with G proteins,
      the cloned mouse delta opioid receptor was solubilized, and the G proteins
      associated with the receptor were identified through coimmunoprecipitation of the
      receptor/G protein complexes with antisera directed against different G(alpha)
      and G(beta) subunits. The delta receptor associates with G(i alpha1), G(i
      alpha3), G(o alpha), G(beta1) and G(beta2) subtypes. On agonist binding to the
      receptor, a greater proportion of the receptor is associated with G(i alpha) than
      with G(o alpha), G(i alpha1) dissociates from the receptor and G(i alpha2)
      associates with the receptor, whereas G(i alpha3) and the G(beta) subunits remain
      coupled to the delta receptor. These findings reveal dynamic changes in the G
      proteins associated with the receptor after agonist binding that may be linked to
      the activation of the delta receptor. In addition to pertussis toxin-sensitive G
      proteins, the delta receptor physically interacts with the pertussis toxin
      insensitive G proteins G(q alpha) and G(z alpha). These interactions may be
      critical in linking delta receptors to phospholipase C. The diversity of G
      proteins associated with the delta opioid receptor may form the basis for the
      selective coupling of these receptors to multiple cellular effector systems.

PMID- 9190887
TI  - Selective serotonin reuptake inhibitors dissociate fenfluramine's anorectic and
      neurotoxic effects: importance of dose, species and drug.
AB  - Fenfluramine, a clinically prescribed appetite suppressant, has been found to
      damage brain serotonin (5-HT) neurons in every animal species tested to date.
      Recent findings indicate that fluoxetine, a selective 5-HT reuptake inhibitor
      (SSRI), can prevent fenfluramine-induced 5-HT neurotoxicity without blocking
      fenfluramine-induced appetite suppression. The purpose of our studies was several
      fold: 1) To determine whether the ability for fluoxetine to dissociate
      fenfluramine-induced anorexia and neurotoxicity is dose-related; 2) to ascertain
      whether other SSRIs also prevent fenfluramine-induced neurotoxicity without
      altering its anorectic effect; 3) to determine whether similar
      fluoxetine/fenfluramine interactions are seen in another animal species (i.e.,
      mice) and 4) to determine whether decreases in food intake seen after the
      fluoxetine/fenfluramine combination can be attributed to nonspecific behavioral
      suppression. Results from our studies indicate that fluoxetine's effects are,
      indeed, dose-related, because higher doses of fluoxetine are required to protect
      against the 5-HT neurotoxic effects of higher doses of fenfluramine. Further, our
      results indicate that fluoxetine's effects generalize to all other SSRIs tested
      (citalopram, paroxetine and sertraline), as well as to other species (mice).
      Finally, our results demonstrate that anorexia in animals receiving the
      fenfluramine/fluoxetine combination is not secondary to nonspecific behavioral
      suppression, because water intake is increased although food intake is decreased
      in the same animals. Together, these data suggest that the anorectic and 5-HT
      neurotoxic effects of fenfluramine may involve different mechanisms, and that by
      combining fenfluramine with SSRIs, it may be possible to exploit fenfluramine's
      clinically useful properties (e.g., anorexia) without risking brain 5-HT neural
      injury.

PMID- 9190888
TI  - Investigation of aortic CYP3A bioactivation of nitroglycerin in vivo.
AB  - Nitroglycerin (GTN) has been used to treat heart disease for many years. It is
      generally believed that GTN is a prodrug; however, the mechanism for GTN
      bioactivation remains unknown. Recent studies, using hepatic microsomes, have
      suggested the involvement of cytochrome P450 3A (CYP3A) in GTN biotransformation.
      Here, we used an animal model to test the hypothesis that aortic CYP3A plays a
      role in the bioactivation of GTN in vivo. Ketoconazole (KCZ), a potent CYP3A
      inhibitor, was given to rats (50 mg/kg i.p.) 1 hr before a bolus dose of GTN (2
      mg/rat i.v.). KCZ decreased GTN-induced cGMP (cyclic guanosine monophosphate)
      levels by 20 to 30% (P < .05), without affecting basal or S-nitroso, N-acetyl
      penicillamine-induced levels of cGMP. When rats received dexamethasone (DEX, 30
      mg/kg, 4 days i.p.), a strong CYP3A inducer, they exhibited a significant
      (approximately 50%) higher cGMP response to GTN than the control group. When rats
      received the combination treatment of both DEX and KCZ, they responded to GTN to
      the same extent as control rats. Although the effect of KCZ on aortic CYP3A
      activity cannot be detected (activity in control rats is below the detection
      limit), KCZ markedly inhibited CYP3A activity in rat livers (2.02 +/- 0.04 vs.
      0.31 +/- 0.04 nmol/mg prot/min, P < .05, in control vs. KCZ-treated rats,
      respectively) and in DEX pretreated rat aorta (0.145 +/- 0.036 vs. 0.042 +/-
      0.037 nmol/mg prot/min, P < .05, in rats treated with DEX alone vs. rats treated
      with both DEX and KCZ, respectively). KCZ did not elicit an effect on aortic
      glutathione S-transferases, another major metabolic enzyme responsible for GTN
      biotransformation. DEX enhanced the aortic GST mu activity by 3-fold. However,
      the activity of GST in aorta did not correlate with the cGMP response to GTN. In
      conclusion, our results demonstrate that CYP3A activity in aorta is correlated
      with GTN bioactivation in vivo, but the contribution of this enzyme to overall
      GTN bioactivation is limited.

PMID- 9190889
TI  - Affinity labeling displays the stepwise activation of ICE-related proteases by
      Fas, staurosporine, and CrmA-sensitive caspase-8.
AB  - The activation of multiple interleukin-1beta converting enzyme-related proteases
      (caspases) in apoptotic mammalian cells raises questions as to whether the
      multiple active caspases have distinct roles in apoptotic execution as well as
      how these proteases are organized in apoptotic signaling pathways. Here we used
      an affinity-labeling agent, YV(bio)KD-aomk, to investigate the caspases activated
      during apoptotic cell death. YV(bio)KD-aomk identified six distinct polypeptides
      corresponding to active caspases in Fas-stimulated Jurkat T cells. On
      staurosporine treatment, four polypeptides were detected. Competition experiments
      showed that the labeled caspases have distinct substrate preferences. Stepwise
      appearance of the labeled caspases in each cell death event was consistent with
      the view that the activated caspases are organized into protease cascades.
      Moreover, we found that stepwise activation of caspases similar to that induced
      by Fas ligation is triggered by exposing non-apoptotic Jurkat cell extracts to
      caspase-8 (MACH/FLICE/Mch5). Conversely, CrmA protein, a viral suppressor of Fas
      induced apoptosis, inhibited the protease activity of caspase-8. Overall, these
      findings provide evidence that caspase-8, a CrmA-sensitive protease, is
      responsible for initiating the stepwise activation of multiple caspases in Fas
      stimulated cells.

PMID- 9190890
TI  - Radiation-induced apoptosis is not enhanced by expression of either p53 or BAX in
      SW626 ovarian cancer cells.
AB  - The p53 protein is known to play a central role in mediating G1 arrest or
      apoptosis in response to ionizing radiation in some cell types. It has been
      proposed that the link between p53 and induction of apoptosis is provided in part
      by p53-mediated upregulation of BAX. In this study, we used the human SW626
      ovarian cancer cell line, which lacks functional p53, to further investigate the
      relationship between wildtype p53, BAX, and apoptosis. SW626 cells expressing a
      temperature sensitive (ts) p53 mutant did not undergo G1 arrest or apoptosis and
      did not exhibit enhanced sensitivity to radiation at the permissive temperature
      of 32 degrees C. The tsp53 protein was functional in these cells as evidenced by
      rapid induction of p21 at 32 degrees C, but not at 37 degrees C. Interestingly,
      restoration of wildtype p53 function at 32 degrees C was not associated with BAX
      upregulation. In addition, stable overexpression of BAX in SW626 cells was not
      capable of enhancing apoptotic cell death in response to radiation. Thus, failure
      of p53 to upregulate BAX is not the sole reason for its inability to promote
      radiation-induced apoptosis in SW626 cells. Taken together, our data suggest that
      neither p53 nor BAX upregulation is sufficient for the induction of apoptosis in
      response to genotoxic damage in some cell types.

PMID- 9190891
TI  - Apoptosis in small intestinal epithelial from p53-null mice: evidence for a
      delayed, p53-independent G2/M-associated cell death after gamma-irradiation.
AB  - The death of small intestinal epithelial cells has been characterized and
      quantitated after irradiation of mice rendered homozygously null for the p53
      gene. In wild-type animals homozygous for p53 a rapid (4.5 h) elevation of p53
      protein was observed in the proliferative compartment of the crypts after 8 Gy of
      irradiation. Cells underwent cell death by apoptosis in this region. We had
      reported previously a total repression of apoptosis in small intestinal crypt
      epithelia 4.5 h after the gamma-irradiation (8 Gy) of p53 homozygously null
      animals. Thus, while 400 apoptotic cells were observed in 200 half crypts taken
      from wild-type animals at 4.5 h, this fell to background levels (10-30) in the
      p53 null animals (Merritt et al., 1994) and did not increase by 12 h. However, we
      have now found a delayed initiation of a p53-independent apoptosis after 8 Gy of
      gamma-radiation: at 24 h, approximately 100 apoptotic cells were observed in 200
      half crypts. This late wave of apoptosis was not observed after 1 Gy of gamma
      radiation. The morphological appearance of this p53-independent apoptosis
      suggested that death may have arisen as the result of aberrant mitosis. Analysis
      of the regeneration of crypts 3 days after irradiation of mice with between 11
      and 17 Gy showed that there was no significant increase (P=0.135) in the
      potential of clonogenic cells from the p53 null animals to repopulate the crypts.
      The data support the idea that a p53-independent apoptotic mechanism permits the
      engagement of apoptosis, probably by a mitotic catastrophe, after 8 Gy of gamma
      irradiation in vivo and that a loss of p53 does not make these epithelial cells
      radioresistant in vivo to doses of 8 Gy and above. In contrast, irradiation with
      1 Gy failed to induce a p53-independent apoptosis in vivo, suggesting that the
      p53 'sensor' of damage was more sensitive than that engaging the p53-independent
      mechanism of cell death.

PMID- 9190892
TI  - Inhibition of tumor growth and metastasis of human breast cancer cells
      transfected with tissue inhibitor of metalloproteinase 4.
AB  - We recently identified, cloned, and characterized a novel human tissue inhibitor
      of metalloproteinases-4, TIMP-4 (Greene et al., 1996). To determine if TIMP-4 can
      modulate the in vivo growth of human breast cancers, we transfected a full-length
      TIMP-4 cDNA into MDA-MB-435 human breast cancer cells and studied the orthotopic
      growth of TIMP-4-transfected (TIMP4-435) versus control (neo-435) clones in the
      mammary fat pad of athymic nude mice. TIMP4-435 clones expressed TIMP-4 mRNA and
      produced anti-metalloproteinase (MMP) activity, while neo-435 clones did not
      express TIMP-4 mRNA or produce detectable anti-MMP activity. Overexpression of
      TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion
      assay. When injected orthotopically into nude mice, TIMP-4 transfectants were
      significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes;
      and in an axillary lymph node and lung metastasis as compared with controls.
      These results suggest the therapeutic potential of TIMP-4 in treating cancer
      malignant progression.

PMID- 9190893
TI  - Deletion of c-myb exon 9 induced by insertion of repeats.
AB  - A simple repeat was found to be inserted into exon 9 of the c-myb gene in three
      out of 20 bovine T lymphomas. The repeat was composed of multiple copies of a 12
      nucleotide motif and had no significant homology to the sequences reported so
      far. Tumor cells containing the repeat expressed two kinds of c-myb mRNA: (1) are
      that included the repetitive sequence in exon 9, and (2) are that lacked the
      whole sequence of exon 9. Transfection of an expression vector containing exon
      and intron sequences and reverse transcriptase-polymerase chain reaction (RT-PCR)
      analysis of the mRNA demonstrated that the insertion of the repeat enhanced exon
      skipping of the transfected minigene. These observations imply that the insertion
      of the repeat may enhance exon skipping of the c-myb pre-mRNA. Although the
      transcription-activating activity by the c-Myb with the repeat was low, that by
      the c-Myb without exon 9 was three- to eightfold higher than the wild-type c-Myb.
      These data suggest that insertion of the 12-nucleotide repeat in codon 359 may
      result in c-Myb proteins having high- and low-transcription-activating activity.

PMID- 9190894
TI  - Functional interaction of the HTLV-1 transactivator Tax with activating
      transcription factor-4 (ATF4).
AB  - The Tax protein of the Human T-cell Leukemia Virus (HTLV) activates the
      expression of viral mRNA through a three 21 bp repeat enhancer located within the
      HTLV-1 LTR. Since Tax does not bind to the 21 bp DNA repeats directly, it has
      been speculated that Tax interacts with cellular protein(s) which mediate binding
      to the enhancer. We employed the yeast two hybrid system to identify host
      proteins that are potentially relevant to Tax transactivation. We identified a
      Tax binding protein encoded from a cDNA expression library derived from
      peripheral blood lymphocytes. The corresponding cDNA has sequence identity with a
      known transcription factor, activating factor-4 (ATF-4). ATF-4 also binds to GST
      Tax fusion protein in vitro. Tax mutants that did not transactivate the HTLV-1
      LTR also failed to bind ATF-4. The critical domain for Tax binding resides in a
      85 amino acid stretch in the C-terminus of ATF-4, which contains the basic domain
      and leucine zipper. We further demonstrated that both full length and N-terminal
      truncated ATF-4 were able to enhance Tax transactivation. Thus, ATF-4 may act as
      an adapter between Tax and the TRE (Tax responsive element), and play an
      important role in Tax-mediated transactivation.

PMID- 9190895
TI  - Transforming activity and mitosis-related expression of the AKT2 oncogene:
      evidence suggesting a link between cell cycle regulation and oncogenesis.
AB  - The AKT2 oncogene encodes a protein-serine/threonine kinase containing a
      pleckstrin homology domain characteristic of many signaling proteins. Recently,
      it was shown that AKT2 kinase activity can be induced by platelet-derived growth
      factor through phosphatidylinositol-3-OH kinase, suggesting that AKT2 may be an
      important signal mediator that contributes to the control of cell proliferation.
      We previously reported amplification and overexpression of AKT2 in human cancers.
      To investigate the transforming activity of AKT2, we used a retrovirus-based
      construct to express AKT2 in NIH3T3 cells. Overexpression of AKT2 was found to
      transform NIH3T3 cells, as determined by growth in soft agar and tumor formation
      in nude mice. The oncogenic activity of AKT2 was diminished by truncation of a 70
      amino acid proline-rich region at the carboxyl-terminus. To facilitate the
      characterization of AKT2, we generated monoclonal and polyclonal antibodies
      against this protein. AKT2 was localized to the cytoplasm by cell fractionation
      experiments, immunocytochemistry, and immunofluorescence. Protein levels were
      more abundant in mitotic cells than in interphase cells. Western blot analysis of
      synchronized pancreatic cancer cells demonstrated that the expression level of
      AKT2 protein in mitotic cells is three to fivefold higher than in their
      interphase counterparts. A time-course study of phytohemagglutinin-stimulated
      lymphocytes revealed that AKT2 mRNA and AKT2 protein levels are highest 48-72 h
      after addition of mitogen, when cells are actively dividing. These data suggest
      that AKT2 could play a significant role in cell cycle progression and that the
      oncogenic activity of overexpressed AKT2 may be mediated by aberrant regulation
      of cellular proliferation.

PMID- 9190896
TI  - Stimulated human leukocytes cause activating mutations in the K-ras
      protooncogene.
AB  - Human tissues which are chronically infiltrated with inflammatory leukocytes are
      more likely to develop malignancies than non-inflamed tissues, however the
      mechanism(s) by which leukocytes contribute to carcinogenesis is unknown.
      Stimulated human leukocytes release superoxide anion and hydrogen peroxide which,
      in the presence of iron, can be converted into the potent oxidant, hydroxyl
      radical (.OH). Previous studies have shown that leukocyte-derived .OH (or a .OH
      like species) can cause DNA damage, however a relationship between leukocyte
      induced DNA damage and carcinogenesis has not been established. The present
      report demonstrates that leukocyte-derived .OH-induced DNA damage can cause K-ras
      oncogene activation, and suggests that there may be a characteristic pattern of
      .OH-induced K-ras oncogene activation. Since activation of the K-ras oncogene is
      believed to play a crucial role in the pathogenesis of many human malignancies,
      .OH-induced K-ras oncogene activation could be an important mechanism by which
      human leukocytes contribute to carcinogenesis.

PMID- 9190897
TI  - Geldanamycin-stimulated destabilization of mutated p53 is mediated by the
      proteasome in vivo.
AB  - Mutation of the tumor suppressor gene p53 is the most common genetic abnormality
      detected in human cancers. Wild type p53 is a short-lived protein with very low
      basal intracellular levels. Most mutated forms of the protein, however, display
      markedly increased intracellular levels as an essential feature of their positive
      transforming activity. In this report, we have used selective inhibitors of the
      20S proteasome to demonstrate that processing of p53 by ubiquitination and
      proteasome-mediated degradation is impaired by commonly occuring mutations of the
      protein. We found that this impairment of p53 turnover can be reversed by
      treatment of tumor cells with the benzoquinone ansamycin, geldanamycin, leading
      to a marked reduction in intracellular p53 levels. Finally, using cells which
      over-express a mutant p53 protein, we were able to demonstrate that restoration
      of proteasome-mediated degradation by geldanamycin is accompanied by p53
      polyubiquitination. Although much remains to be learned about the mechanisms
      involved, our data demonstrate that selective de-stabilization of mutant
      transforming proteins such as p53 can be achieved pharmacologically with agents
      such as geldanamycin which modify the function of molecular chaperone proteins
      within tumor cells.

PMID- 9190898
TI  - Expression of CD44 isoforms in neuroblastoma cells is regulated by PI 3-kinase
      and protein kinase C.
AB  - With respect to a potential role for CD44 in neuronal tumors, we investigated the
      regulation of variant CD44 exon containing isoforms (CD44V) in the human
      neuroblastoma cell line SK-N-SH in response to treatment with differentiation
      inducing and mitogenic factors. While the standard form of CD44 was expressed at
      high levels in both treated and untreated cells, variant isoforms were strongly
      upregulated in response to treatment with 12-O-tetradecanoyl phorbol-13-acetate
      (TPA), insulin-like growth factor-1 (IGF-1) and platelet-derived growth factor
      (PDGF) as shown by RT-PCR and immunofluorescence. One of the CD44 isoforms
      contains sequences encoded by variant exon v6 (CD44V6), which was originally
      described as a metastasis-associated antigen. Using specific inhibitors, we
      explored the signal transduction pathways involved in the expression of variant
      CD44. GF-109203X, a specific inhibitor of protein kinase C effectively blocked
      TPA- and IGF-1-upregulated expression of CD44v6. Wortmannin, a specific inhibitor
      of phosphoinositide 3-kinase (PI 3-kinase) partly reduced IGF-1 and PDGF induced
      CD44v6 expression. The induction of CD44V by TPA, IGF-1 or PDGF was correlated
      with an increased cellular binding to hyaluronic acid, a major counterreceptor
      for CD44. The increased binding caused by TPA or IGF-1 could specifically be
      blocked by the above inhibitors. Thus, PKC and PI 3-kinase are likely to
      transduce growth factor induced signals that upregulate specific CD44 splice
      variants.

PMID- 9190899
TI  - Myc represses the growth arrest gene gadd45.
AB  - The c-Myc protein strongly stimulates cellular proliferation, inducing cells to
      exit G0/G1 and enter the cell cycle. At a molecular level, Myc prevents growth
      arrest and drives cell cycle progression through the transcriptional regulation
      of Myc-target genes. Expression of the growth arrest and DNA damage inducible
      gene 45 (gadd45) is elevated in response to DNA damaging agents, such as ionizing
      radiation via a p53-dependent mechanism, upon nutrient deprivation, or during
      differentiation. Gadd45 holds a vital role in growth arrest as ectopic expression
      confers a strong block to proliferation. Exposure of quiescent cells to mitogen
      stimulates a rapid increase in c-Myc expression which is followed by the
      subsequent reduction in gadd45 expression. The kinetics of these two regulatory
      events suggest that Myc suppresses the expression of gadd45, contributing to
      G0/G1 phase exit of the cell cycle. Indeed, ectopic Myc expression in primary and
      immortalized fibroblasts results in the suppression of gadd45 mRNA levels, by a
      mechanism which is independent of cell cycle progression. Using an inducible
      MycER system, rapid suppression of gadd45 mRNA is first evident approximately 0.5
      h following Myc activation. The reduction in gadd45 mRNA expression occurs at the
      transcriptional level and is mediated by a p53-independent pathway. Moreover, Myc
      suppression and p53 induction of gadd45 following exposure to ionizing radiation
      are non-competitive co-regulatory events. Myc suppression of gadd45 defines a
      novel pathway through which Myc promotes cell cycle entry and prevents growth
      arrest of transformed cells.

PMID- 9190900
TI  - Cell-cycle progression is not essential for c-Myc to block differentiation.
AB  - The c-myc proto-oncogene has been shown to cause blockages to differentiation in
      many cell lineages. Although the mechanism by which c-Myc affects this process
      remains unknown, it is considered that it might result indirectly as an outcome
      of the continued cell-cycle progression invoked by c-Myc in cells which must
      growth arrest in order to differentiate. However, as there is little evidence to
      support this hypothesis, it is equally possible that a differentiation blockage
      occurs through a mechanism independent of c-Myc's involvement in cell-cycle
      progression. To explore this possibility we utilised a differentiation-defective
      variant of the U937 cell line, which still responds to the differentiation
      inducer by undergoing rapid growth arrest. Analysis of this line during growth
      arrest revealed that, although the expression of the Myc target gene, ornithine
      decarboxylase (ODC) was down-regulated, the cells differed from those of the
      parental line in that they continued to express high levels of c-Myc protein, but
      did not maintain high levels of expression of the Myc antagonists, mad1 and mxi1.
      Moreover, antisense down-regulation of the c-Myc protein levels in these growth
      arrested cells revealed that this continued c-Myc expression was essential for
      their differentiation blockage. These data therefore indicate that c-Myc can
      block differentiation by a mechanism dissociated from its ability to direct cell
      cycle progression or the expression of ODC.

PMID- 9190901
TI  - ETS1, NFkappaB and AP1 synergistically transactivate the human GM-CSF promoter.
AB  - Activation of helper T cells results in coordinate expression of a number of
      cytokines involved in differentiation, proliferation and activation of the
      haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM-CSF)
      is one such cytokine, whose increased expression results mostly from increases in
      transcription. Cis-acting elements with NFkappaB, AP1 and ETS-like binding motifs
      have been identified in the promoter region of the GM-CSF gene, and are important
      or essential for transcriptional activity following T cell activation. ETS1 is a
      transcription factor of the ETS family that is expressed in T cells. We have
      previously shown that ETS1 can transactivate GM-CSF in Jurkat T cells, but only
      after the cells have been stimulated by treatment with PMA and ionomycin, agents
      that mimic T cell activation. Thus we proposed that ETS1, which is expressed
      constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible
      factors. Here we show that ETS1 can transactivate a GM-CSF reporter construct in
      unstimulated Jurkat cells, providing that either NFkappaB or AP1 transcription
      factors are supplied by co-transfection. We confirm that binding of endogenous
      NFkappaB and AP1 is induced following PMA/ionomycin treatment of T cells.
      Transactivation by ETS1, NFkappaB and AP1 is synergistic, and mutation of the
      individual binding sites reveals that the transcriptional activities of these
      factors are interdependent. Our results suggest that constitutive ETS1, and
      inducible NFkappaB and AP1, cooperate as part of a higher order transcriptional
      complex in activated T cells.

PMID- 9190903
TI  - Mice lacking reduced nicotinamide adenine dinucleotide phosphate oxidase activity
      show increased susceptibility to early infection with Listeria monocytogenes.
AB  - Mice lacking the gp91 protein of reduced nicotinamide adenine dinucleotide
      phosphate oxidase showed heightened susceptibility to Listeria infection. The
      enhanced susceptibility was noted 2 days after infection, the usual peak time of
      the neutrophil-dependent lesion in the liver. Infected gp91phox -/- mice had an
      increase of approximately 30-fold in Listeria in the liver and an increase in the
      number of microabscesses. The study of the gp91phox mice underscores the early
      role of the neutrophil and of an oxidative burst in this infection with an
      intracellular pathogen. These results contrast with others showing that the late
      macrophage-dependent stage of the infection is dependent on nitric oxide.

PMID- 9190902
TI  - Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair
      of oxidative DNA damage.
AB  - We report the cloning of a human homolog of the yeast OGGC1 gene, which encodes a
      DNA glycosylase that excises an oxidatively damaged form of guanine, 8
      hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine). Since the deduced amino
      acid sequence (68 amino acids) of a human expressed sequence tag, N55394, matched
      a short stretch of yeast OGG1 protein with greater than 40% amino acid identity,
      a full length cDNA clone was isolated from a HeLa cell cDNA library with the
      N55394 clone as a probe. The cDNA clone encodes a predicted protein of 345 amino
      acids which is homologous to yeast OGG1 protein throughout the entire polypeptide
      sequence and shares 38% amino acid identity with yeast OGG1 protein. Moreover, we
      found that both a human homolog and yeast OGG1 protein possess two distinct DNA
      binding motifs, a helix-hairpin-helix (HhH) motif and a C2H2 zinc finger like
      motif, and a domain homologous to human and E. coli MutY proteins. Expression of
      a human homolog suppressed spontaneous mutagenesis of an E. coli (mutM mutY)
      mutant as in the case of yeast OGG1 protein. The gene was ubiquitously expressed
      in a variety of human organs and mapped to chromosome 3p26.2. These results
      strongly suggest that the gene isolated here is a human counterpart of the yeast
      OGGI gene and is involved in the repair of oxidative DNA damage in human cells.

PMID- 9190904
TI  - Specialization of mucosal follicular dendritic cells revealed by mucosal
      addressin-cell adhesion molecule-1 display.
AB  - Follicular dendritic cells (FDC) in the mucosal lymphoid organs, Peyer's patches
      (PP), display mucosal vascular addressin-cell adhesion molecule-1 (MAdCAM-1).
      MAdCAM-1 decorates interlacing dendritic cells throughout PP follicles and is
      accentuated on FDC of the germinal center (GC) light zone and on "junctional"
      dendritic cells overlapping the B/T border and subepithelial dome region, sites
      associated with microenvironmental homing decisions. In contrast, MAdCAM-1 is
      rarely displayed by coronal or junctional FDC in peripheral lymph node follicles
      and is largely confined to the GC after lymph node immunization. FDC-associated
      MAdCAM-1 plays a prominent role in lymphocyte adhesion to GC in PP frozen
      sections and participates significantly in binding to GC in chronically
      stimulated lymph nodes and spleen, but not to GC in lymph nodes after primary
      immunization (where binding is dominated by vascular cell adhesion molecule-1).
      Differential display of MAdCAM-1 by FDC could contribute to the specialization of
      mucosal vs nonmucosal immune responses.

PMID- 9190905
TI  - Corticosteroids inhibit IL-12 production in human monocytes and enhance their
      capacity to induce IL-4 synthesis in CD4+ lymphocytes.
AB  - We examined the effects of corticosteroids on IL-12 production by human monocytes
      and on cytokine synthesis in T cells. To distinguish the effects of
      corticosteroids on the APC used to activate the T cell from direct effects of
      corticosteroids on the T cell, experiments were performed by exposing the APC and
      not the T cell to corticosteroids. We found that corticosteroids significantly
      inhibited the production in monocytes of IL-12, a cytokine that is extremely
      potent in enhancing IFN-gamma and inhibiting IL-4 synthesis in T cells. We
      demonstrated that reduced production of IL-12 in corticosteroid-treated monocytes
      resulted in a decreased capacity of the monocytes to induce IFN-gamma and an
      increased ability to induce IL-4 in T cells. These results suggest that although
      corticosteroids may be beneficial for the treatment of asthma or allergic disease
      due to direct inhibitory effects of corticosteroids on cytokine synthesis in T
      cells, chronic corticosteroid therapy may indirectly exacerbate the long-term
      course of allergic disease. This deleterious effect of corticosteroids would
      result from a limitation in IL-12 production in tissue monocytes and macrophages,
      which would enhance production of Th2 cytokines (which augment allergic disease),
      and would reduce production of Th1 cytokines (which attenuate allergic disease)
      in T cells that subsequently infiltrate the tissues.

PMID- 9190906
TI  - Autocrine and paracrine regulation of human T cell IL-10 production.
AB  - We confirm that IL-10 is produced comparatively late after the activation of
      human T cells via CD3 stimulation, after IL-2 and IFN-gamma. Furthermore we show
      that IL-10 production by human T cell lines, such as IFN-gamma and IL-2, is
      inhibited by the immunosuppressive drugs cyclosporin A and FK506. However, a
      third immunosuppressive drug, rapamycin, normally associated with inhibiting the
      effects, but not the production, of cytokines, inhibited IL-10, but not IFN
      gamma, production. This implies that IL-10 induction may be a secondary event in
      T cell activation. Since IL-2 is the major growth factor for T cells and is
      detected before IL-10, we focused on this factor as a potential activator of IL
      10 production. We showed that IL-10 production by human T cell lines stimulated
      by immobilized anti-CD3 in the presence of neutralizing Abs to IL-2 and IL-2R
      (anti-CD25) was inhibited, whereas addition of exogenous IL-2 enhanced IL-10
      production, indicating that IL-10 production by human T cells can be driven by
      stimulation via IL-2. As the IL-2R shares the common gamma-chain component with
      IL-4, IL-7, and IL-15, we investigated the possibility that they may all enhance
      anti-CD3-induced IL-10 production and established that this was the case. Since
      IL-10 has been previously described as a direct inhibitor of Ag presentation and
      of IL-2 production, our finding that IL-2 is capable of inducing its own
      inhibitor demonstrates a feedback mechanism within the immune system that could
      limit ongoing T cell activation and possibly inflammation.

PMID- 9190907
TI  - Close phenotypic and functional similarities between human and murine alphabeta T
      cells expressing invariant TCR alpha-chains.
AB  - Several studies have demonstrated the existence of a murine NK1.1+ alphabeta T
      cell subset expressing V alpha14+ TCR alpha-chains with highly conserved
      invariant junctional sequences and able to secrete Th2 cytokines when exposed to
      CD1+ stimulator cells. In humans, alphabeta T cells carrying invariant V alpha24+
      TCR alpha-chains highly homologous to those expressed by murine NK1.1 cells have
      been recently described. Here we show that these cells (referred to as V
      alpha24inv T cells) and murine NK1.1+ alphabeta T cells resemble each other in
      several ways. First, like their murine counterparts, T cells expressing high
      levels of V alpha24inv TCRs can be either CD4- CD8- double negative (DN) or CD4+,
      but they never express heterodimeric CD8 molecules. Second, most V alpha24inv T
      cells are brightly stained by NKRP1-specific mAb but not by mAb directed against
      other type II transmembrane proteins of the NK complex. Third, DN and
      particularly CD4+ V alpha24inv T cells are greatly enriched for IL-4 producers.
      The concomitant expression of highly conserved TCRs of a particular set of NK
      markers and of Th2 cytokines in human and murine alphabeta T cells suggests a
      coordinate acquisition of these phenotypic and functional properties.
      Furthermore, the relatively high frequency of human V alpha24inv T cells, which
      are presently shown to represent on average 1/500 PBL, and the high
      interindividual variations of the size of this cell subset under physiologic
      conditions go for a major role played by alphabeta T cells carrying invariant TCR
      in a large array of immune responses.

PMID- 9190908
TI  - IL-2 induces Fas ligand/Fas (CD95L/CD95) cytotoxicity in CD8+ and CD4+ T
      lymphocyte clones.
AB  - IL-2 is a T cell growth factor that has pleiotropic functions in T cell
      differentiation, induction of lymphokine-activated killer cells, and regulation
      of immune responses. In studying TCR triggering of perforin or Fas ligand
      (FasL)/Fas (CD95 ligand/CD95) cytotoxicity in our influenza-specific T cell
      clones, we found that IL-2 can also induce FasL/Fas cytotoxicity. IL-2 induces
      FasL/Fas cytotoxicity in our CD8+ and CD4+ Th1 clones, but not in our CD4+ Th2
      clones. IL-2 induction of cytolytic activity occurs when the CD8+ T cells are
      refractory to IL-2-induced proliferation. This killing is Ag independent, MHC
      unrestricted, and blocked by Fas.Fc fusion protein. IL-2 induces FasL/Fas
      cytotoxicity in a dose-dependent manner, but does not induce high levels of FasL
      expression as detected by flow cytometry. TCR triggered FasL/Fas cytotoxicity is
      detectable in CD8+ and Th1 clones by 3 h and peaks at 6 h; high levels of killing
      are maintained for at least 24 h. Similarly, IL-2 induces FasL/Fas killing in
      CD8+ and Th1 clones within 3 h of stimulation and maintains high levels for at
      least 24 h. TCR-triggered FasL/Fas killing is inhibited by emetine and
      cyclosporin A, whereas IL-2-induced FasL/Fas killing is inhibited by emetine, but
      not by cyclosporin A. These results demonstrate a second mechanism to induce
      FasL/Fas cytotoxicity in CD8+ and Th1 clones and may explain IL-2 induction of Ag
      independent MHC-unrestricted lymphokine-activated killer cell activity.

PMID- 9190909
TI  - Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell
      1 dominant state.
AB  - Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively
      used in Japan for adjuvant cancer therapy. Using a C57BL/6 mouse model, OK-432
      was found to induce multiple cytokines including the Th1 polarizing cytokine IL
      12. Expression of IL-12 protein by murine splenocytes was restricted to
      macrophages and B cells and led to high levels of IFN-gamma production from both
      CD4+ and CD8+ T cells. Of the Th2 cytokines IL-4 and IL-10, only IL-10 protein
      was detected and originated primarily from the adherent cell population. Its
      expression was delayed relative to IL-12. A similar pattern of cytokine induction
      was observed from human PBMCs. OK-432-driven IFN-gamma production was inhibited
      by anti-IL-12 Ab, anti-IL-2 Ab, anti-TNF-alpha Ab, and anti-IL-2R alpha Ab,
      suggesting that IFN-gamma production from Th1 cells is induced by the cooperation
      action of these cytokines through the IL-2R alpha pathway. When compared with
      another widely used immunopotentiator bacillus Calmette-Guerin (BCG), OK-432 was
      a stronger IL-12 and IFN-gamma inducer. Furthermore, the mechanism of IFN-gamma
      induction by OK-432 differed from BCG in that coincident granulocyte-macrophage
      CSF and IL-1 expression played little to no role. These results suggest that OK
      432 is a potent multicytokine inducer, specifically a strong inducer of IL-12,
      and that OK-432 may exert its antitumor effect by promoting a Th1-dominant state.

PMID- 9190910
TI  - Induction of human T helper cell type 1 differentiation results in loss of IFN
      gamma receptor beta-chain expression.
AB  - Differential expression of cytokine receptors accounts for an important
      regulatory mechanism in differentiation of Th1/Th2 subsets. Here, we report that
      human Th0 and Th2 clones constitutively express transcripts for the IFN-gammaR
      beta-chain, whereas mRNA for this signaling component of the IFN-gamma receptor
      is absent in Th1 clones. Activation of T cell clones, however, resulted in a
      transient induction or enhancement of IFN-gammaR beta-chain mRNA expression in
      Th1 clones and Th0/Th2 clones, respectively. IL-12-mediated Th1 cell
      differentiation of naive CD4+, CD45RA+ cord blood T cells, which constitutively
      express IFN-gammaR beta-chain mRNA, resulted in a loss of expression of this
      cytokine receptor chain after 6 to 12 days of culture. In contrast, Th2
      populations, differentiated from CD4+, CD45RA+ cord blood T cells in the presence
      of IL-4, continued to express high levels of IFN-gammaR beta-chain transcripts.
      The loss of IFN-gammaR beta-chain expression in Th1 populations was accompanied
      by a failure of IFN-gamma to induce the expression of the IFN-gamma-inducible
      gene, IFN response factor-1, whereas IFN-gamma was effective in inducing IFN
      response factor-1 mRNA expression in Th0 and Th2 cells. These results indicate
      that down-regulation of the IFN-gammaR beta-chain correlates with impaired IFN
      gamma-induced signaling in Th1 cells. Finally, Th2 populations, generated in the
      presence of both IL-4 and IFN-gamma, expressed levels of IFN-gammaR beta-chain
      transcripts similar to those produced by cells differentiated in the presence of
      IL-4 only, demonstrating that IFN-gamma does not modulate the expression of its
      receptor. Together, these data indicate that human Th0/Th2 and Th1 subsets,
      respectively, can be distinguished based on the expression of the IFN-gammaR beta
      chain.

PMID- 9190911
TI  - The TCR-delta repertoire in human intestine undergoes characteristic changes
      during fetal to adult development.
AB  - The TCR-delta repertoire in adult human intestine is oligoclonal and unique in
      each individual. In the present study, changes in the junctional regions of TCR
      delta transcripts in human intestine that occur during development from fetal to
      adult life were used to characterize fundamental changes in the TCR-delta
      repertoire in the human intestinal tract during ontogeny. At mid-gestation, the
      fetal repertoire was polyclonal, but limited, in its junctional diversity by the
      relative lack of N region nucleotide additions and by the frequent formation of
      coding region joins at regions of short sequence homology. In addition, identical
      TCRDV2 transcripts that resemble canonical TCR-delta sequences in mice were
      present in the intestine of different fetuses. In the early period after birth,
      the intestinal TCR-delta repertoire was polyclonal, and more diverse than the
      fetal repertoire, with junctional regions that contained extensive N nucleotide
      additions and frequently were as complex as those of adults. The intestinal TCR
      delta repertoire showed increasing restriction with age and, by 14 to 17 yr, the
      repertoire was oligoclonal and resembled the repertoire of individuals in the
      sixth to seventh decade. Moreover, the adult TCR-delta repertoire was almost
      identical at multiple sites throughout the intestine, suggesting a model in which
      gammadelta T cell clones, selected by ligands in the intestinal tract, undergo
      expansion and recirculation before lodging throughout the small intestine or
      colon.

PMID- 9190912
TI  - The regulation of p27Kip1 expression following the polyclonal activation of
      murine G0 T cells.
AB  - Polyclonal activation of murine G0 T cells with immobilized anti-CD3 induces
      entry into the cell cycle as well as the subsequent cytokine-dependent
      proliferative response. G0 T cells express high levels of p27Kip1 protein and
      specific mRNA, which decline rapidly following activation. The decline in the
      expression of p27Kip1 and sequestering of the inhibitory protein by cdk4 and cdk6
      correlated with the increase in cdk2 kinase activity during the G1 phase. Anti
      CD3 activation of G0 T cells in the presence of cyclosporin A or rapamycin
      inhibited the down-regulation of p27Kip1, the cellular levels of the inhibitor
      remained high, and the cells remained in the G1 phase. PBu2 activation of G0 T
      cells also did not result in the down-regulation of p27Kip1 and the cells
      remained in G1. In each instance IL-2 restored the down-regulation of p27Kip1,
      resulting in a significant reduction in the level of the inhibitor, and
      stimulated the cells to progress through the cell cycle. Jurkat cells transfected
      with the p27GL-988 plasmid containing +1 to -988 nt of the p27Kip1 promoter
      region and subsequently exposed to rIL-2 resulted in a significant reduction in
      the activity of the p27Kip1 promoter. These findings suggest that in addition to
      providing the signals required for activated T cells to traverse G1/S, IL-2 also
      influences the promoter function of p27Kip1, which effectively induces
      transcriptional down-regulation of the gene.

PMID- 9190913
TI  - Role of CD19 tyrosine 391 in synergistic activation of B lymphocytes by
      coligation of CD19 and membrane Ig.
AB  - CD19 and CD21, which form a complex on B lymphocytes, are required for normal Ab
      responses to T-dependent Ags. Coligation of the CD21/CD19 complex with membrane
      IgM (mIgM) powerfully enhances B cell activation in vitro and in vivo. To
      determine how CD19-mIgM synergy is produced, we examined immediate and downstream
      signaling events after ligation of either complex alone or after CD19-mIgM
      coligation in normal and lymphoblastoid B cells. Ligation of mIgM alone is known
      to result in tyrosine phosphorylation of CD19 and association of CD19 with
      phosphatidylinositol 3-kinase and Vav, and these events are not enhanced by
      coligation. In contrast, tyrosine phosphorylation of phosphatidylinositol 3
      kinase and Vav is markedly enhanced after CD19-mIgM coligation. Coligation also
      results in synergistic, prolonged enhancement of mitogen-activated protein kinase
      activity, relative to ligation of either receptor complex alone. Mutation of CD19
      Y391, the site at which Vav binds, but not mutation of CD19 Y482 and Y513, the
      sites of association with phosphatidylinositol 3-kinase, blocks the enhancement
      of mitogen-activated protein kinase activation. These findings suggest that the
      synergistic enhancement of B cell activation following CD19-mIgM coligation
      results from greater tyrosine phosphorylation of Vav and Vav-dependent enhanced
      activation of mitogen-activated protein kinases.

PMID- 9190914
TI  - Natural killer cell- and macrophage-mediated rejection of concordant xenografts
      in the absence of T and B cell responses.
AB  - Hyperacute, complement-mediated xenograft (Xg) rejection is a first major hurdle
      for xenotransplantation. Thereafter, cellular immunity, including T and B
      lymphocytes, NK cells, and macrophages may become involved as well. In the
      present study, hamster heart Xgs were performed in Leflunomide (LF)-treated nude
      rats. These animals, which are genetically T cell deficient, are known to have a
      strong NK activity. Moreover, xenoantibody (XAb) formation by B lymphocytes was
      previously shown to be blocked in nude rats by LF. Hence, this model was well
      suited to study the role of NK cells and macrophages in Xg rejection. Despite a
      total suppression of XAb formation, LF-treated nude rats rejected hamster heart
      Xgs at a same speed (3 days) as untreated nude rats. NK cells played a major role
      in this rejection process. Indeed, an NK cell-dominated cellular infiltration was
      noticed in the rejected Xgs and the addition of an anti-NK cell serum, anti
      Asialo GM-1 (ASGM-1), to the LF treatment resulted in a significant delay of Xg
      rejection (from 3 days to 6 days; p < 0.0001) that seemed to be mediated by
      activated macrophages because 1) spleens from rejecting animals showed an
      increased percentage of macrophages (ED1+ or ED2+) and 2) rejected Xgs were
      infiltrated predominantly by macrophages. Moreover, splenocytes taken from rats
      that rejected Xgs despite a treatment with LF + ASGM-1 provoked an acceleration
      of Xg rejection when transferred to newly transplanted LF + ASGM-1-treated nude
      rats, and finally, the latter accelerating effect disappeared when macrophages
      were first depleted from the adoptively transferred splenocytes. This study thus
      shows that NK cells and macrophages can be activated in the absence of T cells or
      XAbs to directly reject Xgs.

PMID- 9190915
TI  - Overexpression of the heat shock protein 70 enhances the TCR/CD3- and Fas/Apo
      1/CD95-mediated apoptotic cell death in Jurkat T cells.
AB  - To investigate whether the protective effects of the 70-kDa heat shock protein
      (hsp70) extend to the apoptotic mode of cell death, we transfected Jurkat T cells
      with the gene for the human hsp70 and challenged the cells with an anti-Fas mAb
      or with two different murine anti-CD3 mAbs. The anti-Fas mAb-triggered apoptotic
      cell death and the anti-CD3 mAb-mediated activation-induced cell death were
      significantly enhanced in the gene-transfected Jurkat cells overexpressing hsp70
      compared with the unmanipulated and the vector-transfected cells. On the other
      hand, the well-established protective effect that this protein offers to the
      cells was unaffected, as determined by enhanced viability of gene-transfected
      cells exposed to a lethal heat shock. To investigate the mechanisms that are
      responsible for the increased susceptibility of the gene-transfected cells to
      apoptotic death, we studied the TCR/CD3-initiated events that showed a
      significant down-regulation of the protein tyrosine phosphorylation levels and
      the cytoplasmic free Ca2+ responses. As for the Fas/Apo-1/CD95-mediated early
      events, the activity of protein serine/threonine phosphatases was markedly
      increased in the cells overexpressing hsp70. Our study demonstrates that hsp70
      overexpression offers thermoprotection but enhances TCR/CD3- and the Fas-induced
      apoptotic cell death. This phenomenon is associated with a down-regulation of the
      Ag receptor-initiated early signal transduction pathways and with an up
      regulation of Fas-mediated early metabolic events.

PMID- 9190916
TI  - Fas ligand (CD95L) and B7 expression on dendritic cells provide counter
      regulatory signals for T cell survival and proliferation.
AB  - Activation of T cells is induced efficiently by dendritic cells (DC), but little
      is known about the role of DC in the regulation of T cell death. In this study,
      highly purified DC (DEC-205+, MHC class II(high), B7-1+ [CD80+], B7-2high
      [CD86high], CD40+, CD11c+) grown from normal mouse bone marrow in granulocyte
      macrophage CSF + IL-4 were found to express FasL (CD95L) mRNA by reverse
      transcriptase PCR and to uniformly express FasL by both flow cytometric and
      immunocytochemical analyses. These cells, but not DC propagated from FasL
      deficient (B6.gld) mice, induced dose-dependent increases in DNA fragmentation in
      Fas+ Jurkat T cells over 18 h coculture. Addition of mouse Fas-Fc fusion protein
      at the start of the cultures diminished this effect. Even at high relative
      concentrations, however, B7-2high DC induced only low levels of DNA fragmentation
      in Con A or alloactivated splenic T cells, as determined by radio- or
      spectrofluorometric assays and by in situ nick-end labeling. However, in the
      presence of CTLA4Ig, a molecule that blocks the B7-CD28 costimulatory pathway, DC
      that failed to stimulate in primary MLR induced markedly augmented levels of
      apoptosis in alloactivated T cells. CTLA4Ig treatment also increased the level of
      DNA fragmentation induced by FasL-deficient DC, indicating the existence of
      additional potential (Fas-independent) pathways of DC-induced T cell death. These
      findings suggest that the costimulatory (B7-CD28) and T cell death-inducing
      pathways may play important counter-regulatory roles in dictating the outcome of
      (allogeneic) DC-T cell interactions.

PMID- 9190917
TI  - Evidence for self and nonself peptide partial agonists that prolong clonal
      survival of mature T cells in vitro.
AB  - When examining the effects of peptide analogues without proliferation-inducing
      activity on three human CD4+ T cell clones with distinct TCRbeta recognizing a
      nonself mycobacterial bacillus Calmette-Guerin a (BCGa) peptide fragment
      (EEYLILSARDVLAVVSK)/HLA-DR14 complex, we found that 1) stimulation of T cells
      with a one-residue-substituted analogue or a minimally homologous self peptide
      fragment derived from human connexin 26 (IMILVVAAKEVWGDEQA) can prolong the in
      vitro survival of T cells, in a clone specific-manner; 2) this prolongation is
      associated with the up-regulation of Bcl-xL without proliferation; and 3) these
      peptide-clone combinations are capable of inducing lymphokine secretion. Thus,
      peptide partial agonism may play a role in the survival of not only thymocytes
      but also mature T cells, in the absence of wild-type ligands.

PMID- 9190918
TI  - Differential target cell sensitivity to CTL-activated death pathways in hepatitis
      B virus transgenic mice.
AB  - The current study was designed to explore the relative contribution of Fas ligand
      (FasL), perforin, IFN-gamma, and TNF-alpha-induced death pathways in the
      pathogenesis of CTL-induced liver disease. Hepatitis B virus-specific CTL that
      are genetically unable to produce either FasL, perforin, or IFN-gamma were
      injected into Fas-competent and Fas-deficient hepatitis B virus transgenic mice
      that are either sensitive or resistant to the cytopathic effects of IFN-gamma
      based on the extent to which their hepatocytes retain hepatitis B surface Ag
      (HBsAg). The results of these experiments indicate that FasL- and perforin
      dependent signals are primarily responsible for the induction of liver disease in
      the absence of HBsAg retention, but both signaling pathways must be activated
      simultaneously by the CTL in order to kill the hepatocyte in vivo. In contrast,
      neither FasL nor perforin are required to kill hepatocytes that retain HBsAg as
      long as the CTL secrete IFN-gamma on antigen recognition. Finally the results
      indicate that, irrespective of their HBsAg content, hepatocytes are much less
      sensitive to destruction by TNF-alpha than by the other death pathways. While all
      of these death pathways appear to be operative during a normal CTL response, the
      current experiments suggest that the target cell determines which pathway is
      dominant and selects its mode of execution.

PMID- 9190919
TI  - Involvement of IL-4-producing Vbeta8.2+ CD4+ CD62L- CD45RB- T cells in non-MHC
      gene-controlled predisposition toward skewing into T helper type-2 immunity in
      BALB/c mice.
AB  - It was found that freshly isolated BALB/c CD4+ T cells produced high levels of IL
      4 and IL-10 in response to immobilized anti-CD3 mAb, while C57BL/6 CD4+ T cells
      produced low amounts of IL-4 and IL-10. The high IL-4-producing ability of BALB/c
      mice was demonstrated to be genetically dominant and it was controlled by non-MHC
      gene (or genes). The cells responsible for IL-4 production in BALB/c mice were
      defined as TCRVbeta8.2+ CD4+ CD62L- CD45RB- memory-type T cells, which were
      distinct from NK1.1+ CD4+ NKT cells. Although these memory-type T cells were also
      detected in C57BL/6 mouse spleen at the same frequency, they showed a
      functionally different property from BALB/c CD4+ CD62L- CD45RB- T cells in terms
      of IL-4 production. The fact that germfree BALB/c mouse spleen cells also
      produced high levels of IL-4 suggested that the IL-4 producer in BALB/c mice
      might be developed under the influence of unknown factors other than
      environmental Ags. The CD4+ CD62L- CD45RB- T cells obtained from BALB/c mice
      accelerated the development of IL-4-producing memory-type CD4+ T cells from CD4+
      CD62L+ CD45RB+ naive T cells prepared from OVA-specific TCR-transgenic mice.
      Therefore, IL-4-producing CD4+ CD62L- CD45RB- T cells might play an important
      role in the preferential induction of Th2-dominant immunity in BALB/c mouse
      strain.

PMID- 9190921
TI  - Functional in vivo MHC class II loading by endogenously synthesized glycoprotein
      during viral infection.
AB  - MHC class II presentation of antigenic peptides derived from soluble proteins is
      usually preceded by antigenic uptake via (nonreceptor-mediated) endocytosis by
      professional APCs, followed by processing in endosomal compartments. Although in
      vitro alternative pathways for MHC class II loading have been described for
      certain intracellularly synthesized proteins, the importance of these pathways
      has not been assessed in vivo. We have shown previously that endogenously
      produced membrane-associated glycoprotein (GP) of lymphocytic choriomeningitis
      virus (LCMV), a noncytopathic virus, can be presented in vitro on MHC class II
      molecules in the absence of the invariant chain (Ii), whereas the cytosolic LCMV
      nucleoprotein (LCMV-NP) failed to be presented under the same conditions. Taking
      advantage of this system, we analyzed presentation of LCMV-GP and LCMV-NP in vivo
      in Ii-deficient mice and followed the induced Th cell and B cell responses. At
      early time points after LCMV infection of li-deficient mice, we found in vivo MHC
      class II loading exclusively by the endogenously synthesized LCMV-GP, whereas no
      MHC class II loading by LCMV-NP could be detected. As a direct consequence, LCMV
      specific Th cells exhibited initially only LCMV-GP specificity. In contrast, both
      LCMV-GP- and LCMV-NP-derived epitopes were presented in comparable amounts on
      APCs upon LCMV infection of normal mice, and LCMV-GP- as well as LCMV-NP-specific
      Th cells were comparably induced in vivo. Thus, cell internal MHC class II
      loading pathways are functional in vivo and may become dominant if the usual Ag
      presentation pathways are hampered.

PMID- 9190920
TI  - Regulation of thymocyte lineage commitment by the level of classical protein
      kinase C activity.
AB  - Thymocyte-positive selection involves signaling through TCR and accessory
      molecules, and the signaling intensity appears to be critical for this event. The
      specific inhibitor of classical Ca2+-dependent protein kinase C (cPKC), Go 6976,
      inhibited positive selection in fetal thymus organ culture, indicating that cPKC
      activation is essential for positive selection. The major protein kinase C
      isoforms in CD4+ CD8+ thymocytes are cPKC-alpha, cPKC-beta, and the novel Ca2+
      independent protein kinase C, nPKC-epsilon. To analyze the effect of cPKC
      activation level on positive selection, we used thymocytes from TCR transgenic
      mice with nonselecting and RAG-2 -/- backgrounds as they were developmentally
      arrested at the CD4+ CD8+ stage without positive selection signals. These
      thymocytes survived and acquired CD4/CD8 lineage commitment in suspension culture
      upon transient stimulation with limited concentrations of the selective activator
      of cPKC-alpha and -beta, thymeleatoxin, and the calcium ionophore, ionomycin.
      However, neither 12-deoxyphorbol 13-phenylacetate 20-acetate, which selectively
      activates cPKC-beta, nor ingenol 3,20-dibenzoate, which selectively activates
      nPKC-epsilon, exerted such an effect. The thymeleatoxin/ionomycin concentrations
      corresponded to those that inhibit glucocorticoid-induced apoptosis in thymocytes
      and were lower than those that induce proliferation of mature T cells. The CD4
      lineage commitment required a higher level of cPKC activity than the CD8 lineage
      commitment. CD8alpha or CD4 mRNA expression was down-regulated. Functional helper
      and killer T cells were induced from the CD4 and CD8 lineage-committed cells,
      respectively, by additional stimulation. These results suggest that thymocyte
      lineage commitment in positive selection is regulated by the level of cPKC-alpha
      activity or by the levels of cPKC-alpha and -beta activities.

PMID- 9190922
TI  - Association of the common gamma-chain with the human IL-7 receptor is modulated
      by T cell activation.
AB  - IL-7 acts on both resting and activated T cells. The functional IL-7R is reported
      to consist of two subunits, the ligand binding IL-7R and the common gamma-chain
      (gamma c chain), where IL-7R:gamma c chain association is driven solely by ligand
      binding. However, we now demonstrate that in primary T cells this event is also
      controlled by cellular activation. We show that IL-7R:gamma c chain complexes are
      detected in activated, but not in resting, T cells despite similar levels of
      gamma c chain expression, implying that the gamma c chain is not associated with
      the IL-7R in unstimulated T cells. Furthermore, IL-7R:gamma c chain association
      correlates with the expression of JAK-3 in T cells, but not in transfected COS-7
      cells. The finding that IL-7R:gamma c chain assembly is controlled at a level
      beyond that of receptor expression has important implications for the control of
      cytokine function in T cells.

PMID- 9190924
TI  - TCR-gamma genes are rearranged but not transcribed in IL-7R alpha-deficient mice.
AB  - IL-7, a cytokine produced by bone marrow and thymic stroma, is a growth factor
      for B and T lymphocytes very early in their development. The IL-7R is a
      heterodimer of an alpha-chain that specifically binds IL-7 and the common gamma
      chain, gamma(c), which is also a component of the receptors for IL-2, IL-4, IL-9,
      and IL-15. IL-7 has also been hypothesized to play a role in the differentiation
      of gammadelta T cells, which is supported by the recent findings that mice
      deficient in the alpha-chain of the IL-7R (IL-7R alpha -/-) or IL-7 (IL-7 -/-)
      have a complete absence of gammadelta T cells, but not alphabeta T cells. We show
      in this work that Vgamma4 and Vgamma6 TCR genes are rearranged, and sterile
      Vgamma4 and Vgamma6 TCR-gamma transcripts are expressed in IL-7R alpha -/-
      thymocytes, but these TCR-gamma genes, and Vgamma5, are not transcribed in
      thymocytes from IL-7R alpha -/- mice. RAG-1 and RAG-2 genes are transcriptionally
      active in fetal and adult IL-7R alpha -/- thymocytes. The IL-7-inducible
      transcription factor, STAT5, is not active in the fetal thymus of IL-7R alpha -/-
      compared with IL-7R alpha +/+ mice. These data point to a specific role for IL
      7/IL-7R signaling in regulating the transcriptional activity, possibly mediated
      by STAT5, of the rearranged TCR-gamma complex during development of gammadelta T
      cells, and point to mechanistic differences in the regulation of rearrangement of
      Vgamma4 and Vgamma6 genes vs Vgamma5.

PMID- 9190923
TI  - The CD94/NKG2-A inhibitory receptor complex is involved in natural killer cell
      mediated recognition of cells expressing HLA-G1.
AB  - Human NK cells bear surface receptors that inhibit their cytolytic activity upon
      specific recognition of MHC class Ia Ags; little is known about the capacity of
      class Ib molecules to regulate NK cell function. We have studied the roles of
      different NK inhibitory receptors in recognition of the class Ib HLA-G. To this
      end, we analyzed the ability of an HLA-defective tumor cell line (721.221)
      transfected with the membrane form of HLA-G1, which contains the three external
      domains, to inhibit the cytolytic activity mediated by a panel of NK clones from
      several donors. A substantial proportion of peripheral blood NK clones appeared
      to be significantly inhibited by the HLA-G1-transfected cell line (referred to as
      .221-G1); nevertheless, no relation was observed between the expression and the
      function of serologically identifiable Ig-SF receptors (p58/p70) and specific
      recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG
      soluble fusion proteins specifically bound to 721.221 transfectants bearing their
      corresponding HLA-C ligands, but only a weak reactivity with .221-G1 cells was
      detectable. By contrast, most NK clones blocked by HLA-G1 expressed the CD94/NKG2
      A inhibitory receptor, and moreover, CD94-specific mAbs reconstituted their
      cytolytic activity comparably to anti-HLA class I mAbs. These data support the
      idea that the CD94/NKG2 receptor complex is involved in the recognition of cells
      expressing HLA-G1.

PMID- 9190925
TI  - Stress and autoimmunity: the neuropeptides corticotropin-releasing factor and
      urocortin suppress encephalomyelitis via effects on both the hypothalamic
      pituitary-adrenal axis and the immune system.
AB  - Corticotropin-releasing factor (CRF) exerts a major role in the stress response.
      Both CRF and urocortin, a newly discovered neuropeptide homologous to CRF,
      suppressed experimental autoimmune encephalomyelitis (EAE). Suppression of
      paralysis with CRF involved stimulation of the hypothalamic-pituitary-adrenal
      axis and inhibitory effects on an encephalitogenic T cell line. While CRF
      increased glucocorticoid production, which is known to block EAE, it also
      suppressed EAE in adrenalectomized rats, where glucocorticoid stimulation via CRF
      plays no role. Moreover, the encephalitogenicity of a T cell line exposed to CRF
      in vitro was reduced. Stress may influence autoimmune disease through the
      hypothalamic-pituitary-adrenal axis and directly via the immune system.

PMID- 9190926
TI  - Phosphatidylinositol-based glycolipid-anchored proteins enhance proximal TCR
      signaling events.
AB  - Previous reports suggested that T lymphocyte activation through
      phosphatidylinositol-based glycolipid (GPI)-anchored molecules is dependent on
      surface expression of the TCR. Here we show that stimulation of the TCR in five
      mutant cell lines with deficiencies in GPI biosynthesis fails to induce tyrosine
      phosphorylation of the TCR zeta-chain and ZAP-70, indicating that early events in
      TCR-mediated signal transduction are affected in these mutants. The Src kinases
      Fyn and Lck coprecipitating with activated TCR complexes are significantly less
      kinase active in the GPI-processing mutants than in wild-type cells. These data
      suggest that GPI-anchored proteins may play an important role in the initiation
      of TCR signal transduction by contributing to the accumulation of Src kinase
      activity in the TCR complex.

PMID- 9190927
TI  - Fas ligand-mediated bystander lysis of syngeneic cells in response to an
      allogeneic stimulus.
AB  - Using a mouse allospecific lymph node (LN) CTL (H-2b) response to transplanted
      cells (H-2k), effector cells were shown to lyse C3H/HeJ or L929-Fas (H-2k) target
      cells in either a perforin-dependent or a Fas ligand (FasL)-dependent manner.
      C3H/HeJ.lpr targets or L929 targets lacking Fas were not sensitive to these
      effectors generated in perforin-deficient (Po) mice. By contrast, C3H/HeJ.lpr
      target cells and L929 were as responsive as C3H/HeJ and L929-Fas targets to the
      effectors generated in perforin wild-type (P+/+) mice. To measure potential
      bystander lysis in allogeneic responses, these same effector LN from either
      C57BL/6 P+/+ or P(o) mice were examined for lysis of C3H/HeJ (or C3H/HeJ.lpr) or
      L929-Fas (or L929) cocultured with 51Cr-labeled C57BL/6 (H-2b) target cells.
      Bystander lysis of C57BL/6 targets was observed only in those allogeneic
      responses where FasL was the defined mechanism of lysis. By contrast, perforin
      mediated lysis was restricted by allo-recognition. Syngeneic (H-2b) targets that
      were not sensitive to Fas-mediated lysis were not lysed in a bystander fashion.
      Depletion of subsets of LN Po effectors (b anti-k) demonstrated that CD4+ T cells
      were primarily responsible for FasL-mediated direct and bystander lysis. FasL
      mediated bystander lysis was also observed in H-2k anti-b reactions, except when
      the effectors were FasL mutant (gld). These data suggest that CTL responses to
      foreign Ag may evoke a certain amount of collateral damage to local host Fas
      sensitive cells.

PMID- 9190928
TI  - Aberrant TCR-mediated signaling in CD45-null thymocytes involves dysfunctional
      regulation of Lck, Fyn, TCR-zeta, and ZAP-70.
AB  - CD45 is a transmembrane phosphotyrosine phosphatase expressed on all nucleated
      hemopoietic cells. Targeting of CD45 exon 9 has generated a mouse line completely
      lacking CD45 expression (CD45-null) in which there are severe abnormalities in T
      cell development. Defects in TCR-mediated signals underlying these abnormalities
      have now been investigated using CD45-null T cells. No T cell proliferation was
      detected in response to a CD3 mAb. In thymocytes the p56(lck) and p59(fyn)
      tyrosine kinases were hyperphosphorylated, and p56(lck) was in its inactive
      conformation. Both basal and TCR-stimulated tyrosine phosphorylation of TCR-zeta
      and CD3-epsilon were much reduced, and TCR stimulation induced an abnormal p18
      phosphoisomer of TCR-zeta previously noted in T cells stimulated by altered
      peptide ligands. These defects were associated with the failure of ZAP-70 kinase
      recruitment to the TCR-zeta chain. TCR coupling to the tyrosine phosphorylation
      of several proteins, including HS1 and p120(cbl), was also much reduced. However,
      TCR-induced signaling was not ablated, and significant inositol phosphate and
      calcium signals were observed in CD45-null thymocytes. Our molecular analysis
      suggests that the threshold for TCR signal transduction is greatly increased in
      CD45-null T cells, thus explaining the profound defects in thymic development.

PMID- 9190929
TI  - Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that
      mediated by whole cytotoxic lymphocytes.
AB  - Two pathways have been implicated in the induction of apoptosis by cytotoxic T
      cells: the granule exocytosis pathway and a pathway using CD95 (Fas/APO-1). To
      test whether apoptosis induced by either of these pathways could be blocked by
      Bcl-2, we exposed bcl-2-transfected cells to CTL derived from normal, perforin
      deficient, or CD95 ligand mutant (gld) mice. Although the levels of Bcl-2
      expression achieved were able to protect FDC-P1 and Yac-1 transfectants from a
      variety of apoptotic stimuli, the cells were not protected from cytolysis
      mediated by CTL from any of these sources, by NK cells, or granules isolated from
      CTL. However, Bcl-2 expression significantly inhibited apoptosis induced by
      purified granzyme B and perforin. These results suggest that while Bcl-2 is
      capable of inhibiting the apoptotic pathway utilized by perforin and granzyme B,
      other granule components can bypass this block. We conclude that CTL harbor
      potent killing mechanism(s) in addition to those provided by CD95 ligand or
      perforin and granzyme B that cannot be overcome by Bcl-2.

PMID- 9190930
TI  - IL-6 rescues resting mouse T cells from apoptosis.
AB  - It has previously been demonstrated that mature mouse T cells live for many weeks
      in vivo. In contrast, explanted lymph node or splenic T cells undergo spontaneous
      death within days, suggesting that survival factors supplied in vivo are not
      present in normal tissue culture medium. We discovered that IL-6 can rescue
      resting T cells from apoptosis in vitro. We show that recombinant mouse IL-6 as
      well as IL-6 in endothelial cell supernatants are sufficient to rescue T cells
      from death in the absence of additional cytokines. We show that CD4+ T cells
      express Bcl-2 immediately following isolation from the mouse, but after 24 h in
      culture Bcl-2 is undetectable. If during this time period the T cells are
      incubated with rIL-6, Bcl-2 expression is not down-regulated. It is, therefore,
      possible that IL-6 rescue from death is mediated by maintenance or induction of
      Bcl-2 expression. Addition of rIL-6 does not by itself induce blastogenesis or
      proliferation, and therefore, this cytokine appears to be a true survival factor
      rather than a mitogenic factor for resting T cells. Together, these results
      support a potential role for IL-6 as one of the factors important for prolonging
      resting T cell survival in vivo.

PMID- 9190931
TI  - A naturally processed peptide presented by HLA-A*0201 is expressed at low
      abundance and recognized by an alloreactive CD8+ cytotoxic T cell with apparent
      high affinity.
AB  - In contrast to T cells that respond to peptides presented by self MHC molecules,
      alloreactive T cells recognize determinants expressed on nonself MHC molecules.
      Because current positive selection models suggest that T cell affinity toward a
      nonself MHC molecule would be lower than that toward a self MHC molecule, we
      previously proposed that vigorous alloreactive responses would be generated
      preferentially toward those antigenic peptide complexes presented at the highest
      density on the cell surface. The high abundance of two class I MHC-associated
      peptides that have been identified as allo- or xenoantigens is consistent with
      this hypothesis. We report here the identification of a naturally processed
      peptide YLDPAQQNL that is presented by HLA-A*0201 and recognized by an
      alloreactive T cell clone. This peptide appears to originate from an unknown
      member of the zinc finger proteins. Quantitation by mass spectrometry indicates
      that this peptide is present on the surface at 85 to 125 copies per cell,
      comparable with the density of several other epitopes presented by HLA-A*0201 to
      self MHC-restricted T cells. In addition, based on the affinity of the peptide
      for HLA-A*0201 and the half-maximal peptide concentration required for T cell
      sensitization, this alloreactive T cell appears to have an affinity similar to or
      higher than that of many self MHC-restricted T cells. These data suggest that
      allogeneic responses can be directed against antigenic determinants of low
      abundance and that recognition of alloreactive peptides is not limited by a lower
      affinity of T cells for nonself MHC molecules.

PMID- 9190932
TI  - Intermediate TCR cells in mouse lung: their effector function to induce
      pneumonitis in mice with autoimmune-like graft-versus-host disease.
AB  - The lung comprises lymphocytes even under noninflammatory conditions. We
      investigated the presence of NK cells, extrathymic T cells, and thymus-derived T
      cells in this organ. As shown previously in mouse liver, two-color staining for
      CD3 and IL-2R beta-chain (IL-2Rbeta) identifies CD3- IL-2Rbeta+ NK cells, CD3int
      IL-2Rbeta+ cells (int indicates intermediate; of extrathymic origin), and CD3high
      IL-2Rbeta- cells (high indicates high; of thymic origin). These populations were
      present in the lungs of normal mice in a unique manner (i.e., NK cells > CD3high
      cells > CD3int cells). The proportion of CD3int cells increased in the lung with
      age. In athymic mice, only CD3int cells were detected in the lung. In contrast to
      CD3int cells in the liver, the majority of these cells in the lung did not
      express NK1.1 Ags. Other properties of CD3int cells in the lung were the same as
      those in the liver, e.g., double-negative CD4- 8- cells and gammadelta T cells.
      CD3int cells in the lung contained forbidden clones similar to those in other
      organs. When (B6 x bm12) F1 mice (Ly5.2) were injected with CD3high cells of B6
      Ly5.1 origin, F1 mice fell victim to chronic graft-vs-host disease and
      pneumonitis, showing the expansion of CD3int cells. Almost all of them were of
      recipient origin (Ly5.2+). More importantly, such CD3int cells induced autoimmune
      like pneumonitis when injected into irradiated F1 mice. CD3int cells isolated
      from the lung in mice with graft-vs-host disease exerted autologous cytotoxicity
      against thymocytes in vitro. These results suggest that extrathymic T cells exist
      in the lung and that their expansion may be responsible for inflammatory lung
      diseases.

PMID- 9190933
TI  - A tandem GC box motif is necessary for lipopolysaccharide-induced transcription
      of the type II TNF receptor gene.
AB  - LPS induces the expression of the gene encoding the type II TNF-alpha receptor in
      mononuclear phagocytes. To elucidate the nuclear signaling mechanisms involved in
      this response, a 772-bp fragment of the TNFRII gene promoter was analyzed by
      deletion and site-specific mutagenesis following transient transfection in the
      macrophage-like cell line RAW264.7. A region located between -100 and -75
      relative to the transcription start site was found to be essential for LPS
      sensitivity. This contained a GC-rich region composed of two tandemly arrayed Sp
      1 sites. While mutation of this region confirmed that it was essential for LPS
      sensitivity, the sequence was not able to confer LPS sensitivity upon a
      heterologous promoter. Internal deletion and site-specific mutagenesis of the 100
      bp fragment identified regions immediately flanking an initiator region (Inr)
      site that were also necessary for sensitivity to LPS. Electrophoretic mobility
      shift assays demonstrated that the GC box bound Sp-1 and Sp-3, although the level
      of binding activity did not vary with LPS stimulation. An oligonucleotide probe
      containing nucleotide positions -45 to -18 also bound several protein complexes,
      but these were not enhanced by LPS. These findings indicate that the tandem GC
      box is necessary, but not sufficient, for LPS-mediated transcription of the
      TNFRII gene. A second apparently novel motif, located within 15 nucleotides of
      the Inr, is also necessary.

PMID- 9190934
TI  - The human heavy chain Ig V region gene repertoire is biased at all stages of B
      cell ontogeny, including early pre-B cells.
AB  - The expressed human Ig repertoire is not an equal representation of all V(H)
      segments present in genomic DNA. Studies have shown that a restricted set of V(H)
      gene segments are over-represented in Ab repertoires of fetal/neonatal and adult
      B cells. Additionally, this restricted set of V(H) genes is frequently expressed
      by autoimmune and tumor B cells. To investigate at which developmental stage a
      bias in the repertoire begins, we compared the V(H)3 and V(H)4 family repertoires
      of pre-B and immature B cells from bone marrow and mature B cells from peripheral
      blood of two adults. We found that the V4-34 and V4-59 gene segments of the V(H)4
      family and the V3-23 gene segment of the V(H)3 family dominate the repertoires of
      the surface Ig-negative early pre-B as well as immature and mature B cells.
      Furthermore, the pattern of utilization of other V(H)3 family members suggests
      that certain genes that are frequently rearranged during early stages of B cell
      development are subsequently disfavored during later stages of B cell maturation.
      We conclude that the over-representation of certain V genes could arise from
      sequential mechanisms operating at both early and later stages of B cell
      development. These V(H)-mediated mechanisms might include preferential
      rearrangement and/or efficiency of pairing with the surrogate light chain at the
      surface Ig-negative, early pre-B cell stage and ligand selection at more mature,
      surface Ig-positive, B cell stages.

PMID- 9190935
TI  - An octamer element functions as a regulatory element in the differentiation
      responsive CD11c integrin gene promoter: OCT-2 inducibility during myelomonocytic
      differentiation.
AB  - The integrin CD11c/CD18 mediates leukocyte adhesion to endothelium and other cell
      types and is a receptor for LPS, iC3b, and fibrinogen. CD11c expression is
      restricted to myeloid and activated B cells, is regulated during leukocyte
      differentiation, and constitutes a diagnostic tool for hairy cell leukemia.
      Mapping of in vivo DNA-protein interactions in the CD11c proximal promoter
      revealed three adjacent myeloid-specific interactions, one of which lies on an
      octamer consensus sequence, ATTT GCAT (Oct185). Oct185 disruption increased the
      CD11c promoter activity while decreasing its myeloid differentiation
      responsiveness, indicating that Oct185 contributes to the activity of the CD11c
      promoter and suggesting that Oct185 is a negative regulatory element whose
      function changes during myeloid differentiation. Oct185 is recognized by the
      ubiquitous Oct-1 factor in all cell lineages and by Oct-2 in B lymphoid lineage
      cells. Unexpectedly, Oct-2 binding to Oct185 was induced de novo upon monocytic
      differentiation of U937 and HL-60 cells but not during HL-60 granulocytic
      differentiation, as determined by electrophoretic mobility shift assays and
      immunochemical studies, and Oct-2 complexes were also observed in cultured
      adherent monocytes. Western blotting showed that the pattern of Oct-2 isoforms in
      myeloid cells is similar to that seen in B cells. The Oct-2 up-regulated
      expression in differentiating myeloid cells and its binding to the Oct185
      negative regulatory element suggests its involvement in the differentiation
      regulated activity of the CD11c promoter and might represent an important
      parameter for the myeloid- and B cell-restricted expression of the CD11c/CD18
      integrin and other molecules with similar patterns of expression.

PMID- 9190936
TI  - Regulatory factor X, a bare lymphocyte syndrome transcription factor, is a
      multimeric phosphoprotein complex.
AB  - Regulatory factor X (RFX) is a transcription factor that binds the conserved X1
      box of MHC class II promoters and is essential for transcription of class II
      genes. The subunit structure of the native RFX complex was examined by
      coimmunoprecipitation using polyclonal antisera to the 75-kDa subunit of RFX,
      RFX5. Two polypeptides with apparent masses of 41 and 36 kDa coimmunoprecipitated
      with RFX5 and appear to be subunits of the native RFX complex. Metabolic labeling
      of wild-type and mutant B cells with [32P]orthophosphate demonstrated that each
      of the RFX subunits was phosphorylated in vivo and that the phosphorylation of
      the RFX subunits was independent of the essential MHC class II regulatory factor,
      CIITA. The trimeric RFX complex was also present in fibroblast cells with or
      without IFN-gamma treatment. Both the p41 and p36 subunits were absent in
      immunoprecipitations of RFX5 from lysates of independently established B cell
      lines from bare lymphocyte syndrome complementation groups B and D. Together,
      these results suggest that RFX complex assembly is required for class II
      expression and that the mutations in bare lymphocyte syndrome complementation
      groups B and D result in an inability to assemble the RFX complex.

PMID- 9190937
TI  - Allotype-associated variation in the human gamma3 switch region as a basis for
      differences in IgG3 production.
AB  - High and low serum concentrations of IgG3 are associated with the human G3 m(b)
      and G3 m(g) allotypes, respectively. We previously hypothesized that a low
      frequency of switching is the most likely defect in (g) allotype-positive
      individuals, and therefore analyzed the structure, recombination breakpoints, and
      binding of nuclear proteins to the switch (S)gamma3 regions of these two
      allotypes. There are no allotype-associated differences in the length and basic
      structure of the Sgamma3, since both contain eighteen 79-bp repeats. However, we
      found a number of allotype-associated nucleotide changes. As in the mouse system,
      there is a preferential switching to the B site, or switch nuclear
      protein/nuclear factor-kappaB motif, with a clustering of switch breakpoints at
      the most 5' residue of the B site. The B site sequence used most frequently in
      switching was found to be mutated at this nucleotide in the (g) allotype
      associated Sgamma3. This change was shown by electrophoretic mobility shift assay
      to alter the binding of the switch nuclear protein/nuclear factor-kappaB protein
      to the B site. Taken together, these data suggest that polymorphism within
      Sgamma3 may contribute to allotype-associated differences in IgG3 switching, and
      that specific sequences within the Sgamma3 79-bp repeats could be mechanistically
      important for switch recombination.

PMID- 9190938
TI  - The IL-4 receptor alpha-chain cytoplasmic domain is sufficient for activation of
      JAK-1 and STAT6 and the induction of IL-4-specific gene expression.
AB  - The common gamma-chain (gamma(c)) is a functional component of the IL-4R, yet
      cells lacking gamma(c) are able to respond to IL-4. This has led to the
      suggestion that a surrogate gamma'-chain, which can interact with the IL-4R alpha
      chain to mediate signaling, is expressed on cells lacking gamma(c). An
      alternative possibility is that in the absence of gamma(c), the IL-4R alpha chain
      is able to transduce signals by homodimerization. To test this latter
      possibility, a chimeric receptor containing the extracellular domain of c-kit
      (the stem cell factor (SCF) receptor) and the cytoplasmic and transmembrane
      domains of the IL-4R alpha chain was generated. Treatment of cells expressing the
      chimeric receptor kit/IL-4R alpha with SCF induces activation of the IL-4R alpha
      associated kinase JAK-1 and the transcription factor STAT6. However, tyrosine
      phosphorylation of JAK-3, which associates with gamma(c), is not induced by SCF
      in these cells. SCF-mediated ligation of kit/IL-4R alpha is sufficient to elicit
      IL-4-specific gene expression, including up-regulation of CD23 and synthesis of
      germ-line epsilon transcripts. In the T cell line CTLL2, ligation of kit/IL-4R
      alpha induces cellular proliferation. Finally, in JAK-1-deficient HeLa cells,
      STAT6 activation by IL-4 is completely abolished. Together, these data
      demonstrate that the IL-4R alpha cytoplasmic domain is sufficient to activate JAK
      1 and STAT6 and to induce expression of IL-4 target genes, thus identifying a
      mechanism by which IL-4 signaling can proceed in the absence of JAK-3 and
      gamma(c).

PMID- 9190939
TI  - Four conserved promoter motifs regulate transcription of the gene encoding human
      complement component C2.
AB  - The early complement components of the classical activation pathway of the
      complement cascade include the components C1, C4, C2, and C3. These components
      act in concert to opsonize bacteria, clear immune complexes, and produce
      inflammatory mediators. They are not structurally homologous nor are they
      coordinately regulated. The expression of the early complement components is
      divergent in terms of cytokine responsiveness and tissue specificity. The only
      pattern of expression shared by the early complement components is inducibility
      by gamma-IFN and expression in cells of hepatic or monocytic lineage.
      Nevertheless, four novel conserved promoter motifs were identified in the 5'
      flanking region of multiple early complement component promoters. Mutation of
      these four motifs in the C2 promoter decreased transcription in hepatoma cells in
      transient transfection analyses, and a synthetic promoter consisting of just the
      four motifs supported transcription in hepatoma cells. Electrophoretic mobility
      shift assays demonstrate that three of the four conserved elements bind DNA
      binding proteins in a tissue-specific manner. One DNA-binding protein is
      expressed ubiquitously, but the other three are restricted to cells of monocytic
      or hepatic lineage. Two of the DNA-binding proteins appear to be members of the
      zinc-finger family of transcription factors. Therefore, these four motifs appear
      to bind DNA-binding proteins that may function in the tissue-specific expression
      of C2. Conservation of these four motifs in multiple early complement component
      genes suggests that these may represent a conserved transcriptional strategy.

PMID- 9190940
TI  - The transcription factor B cell-specific activator protein (BSAP) enhances both
      IL-4- and CD40-mediated activation of the human epsilon germline promoter.
AB  - Induction of isotype switching to a particular C(H) gene correlates with the
      transcriptional activation of the same gene in germline configuration. Induction
      of correctly spliced germline transcripts is necessary to target a switch region
      for recombination and switching. Different cytokines activate transcription at
      different germline promoters. Because binding sites for the B cell-specific
      transcription factor BSAP are located upstream of several switch regions in the
      Ig locus, BSAP might play a role in isotype switching by regulating germline
      transcription. We investigated whether BSAP plays a role in the transcriptional
      regulation of the epsilon germline promoter in human B cells. We identified human
      EBV-negative B cell lines that express epsilon germline transcripts upon
      stimulation with IL-4. Electrophoretic mobility shift assay analysis showed that
      the human epsilon germline promoter binds BSAP. BSAP activity was expressed
      constitutively and was not affected by stimulation with IL-4 and/or anti-CD40
      mAb. Reporter assays with constructs containing a luciferase gene driven by the
      epsilon germline promoter, with or without mutations in the BSAP binding site,
      showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated
      up-regulation of human epsilon germline transcription. Furthermore, epsilon
      germline promoter activity was abrogated in REH cells that express a BSAP
      polypeptide truncated in the trans-activation domain. Among the transcription
      factors that regulate epsilon germline expression, BSAP is unique, in that it is
      B cell-specific and is at the merging point of two signaling pathways that are
      distinct but both critical for the induction of IgE switching.

PMID- 9190941
TI  - Adoptive transfer of gut intraepithelial lymphocytes protects against murine
      infection with Toxoplasma gondii.
AB  - Intraepithelial lymphocytes (IEL) of the gut represent a primary immune barrier
      against infection by orally acquired pathogens. Naturally acquired infection with
      Toxoplasma gondii induces the proliferation of CD8+ T cells in both the gut and
      spleen. Gut-derived CD8alpha/beta+ IEL exhibit MHC-restricted cytotoxicity
      against parasite-infected enterocytes and macrophages. In a murine model, we
      demonstrate that the adoptive transfer of IEL obtained from inbred mice at day 11
      postinfection is able to protect against a virulent challenge in syngenic
      recipients. In CBA mice, the parasite cyst load within the brain of the
      recipients receiving primed IEL was reduced by 90%. In BALB/c and C57BL/6 mice, a
      50% decrease in mortality was observed following adoptive transfer of primed IEL.
      To determine the T cell subset responsible for protective immunity, a purified
      CD8alpha/beta+ IEL population was isolated from infected mice at day 11
      postinfection. These cells were able to protect naive mice by adoptive transfer
      against a lethal parasite challenge. RNA analysis by reverse-transcriptase PCR
      revealed that primed CD8alpha/beta+ IEL produce significant message for IFN
      gamma, an essential cytokine for host protection against toxoplasmosis.
      Administration of anti-IFN-gamma at the time of adoptive transfer of primed IEL
      abrogated protection. The adoptive transfer of these protective IEL was not
      restricted to the Ld class I locus. These data demonstrate that IFN-gamma
      producing IEL may be an important primary barrier against acute and perhaps
      recurrent infection with T. gondii.

PMID- 9190942
TI  - Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from
      Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory
      cytokines by macrophages.
AB  - Components of Trypanosoma cruzi able to induce the production of IL-12 and other
      proinflammatory cytokines by macrophages were identified. Murine inflammatory
      macrophages were cultured with live parasites or with cellular components from
      different developmental forms of T. cruzi (i.e., trypomastigotes, amastigotes,
      metacyclic trypomastigotes, and epimastigotes), and the cytokine levels were
      measured after 24 and 48 h. Our results indicate that live trypomastigotes or
      live amastigotes (but not live epimastigotes or live metacyclic trypomastigotes)
      as well as trypomastigote extracts (but not extracts derived from epimastigotes)
      induce IL-12 and TNF-alpha synthesis by macrophages. Such biological activity is
      enhanced in membrane preparations from trypomastigotes. Further enrichment of the
      trypomastigote-derived monokine-inducing factor was obtained by solvent
      extraction and hydrophobic-interaction chromatography. The resultant purified
      molecules are a family of closely related glycoconjugates with predominant
      species at 70 to 80 and 120 to 200 kDa. These molecules are composed of
      carbohydrate chains O-linked to a polypeptide backbone that is anchored to the
      trypomastigote membrane via a glycosylphosphatidylinositol structure. The
      trypomastigote-derived glycoconjugates are active in inducing cytokine synthesis
      by macrophages at concentrations of 100 ng/ml. These effects are highly
      potentiated by IFN-gamma. Mapping of the glycoconjugate molecules to characterize
      the structural requirements for macrophage activation suggested that nonsaturated
      acyl fatty acid chains and periodate-sensitive units from the
      glycosylphosphatidylinositol anchor are important elements for the infective
      trypomastigote form to initiate cytokine synthesis by macrophages.

PMID- 9190943
TI  - TCR beta-chain variable region-driven selection and massive expansion of HLA
      class I-restricted antitumor CTL lines from HLA-A*0201+ melanoma patients.
AB  - Recognition of a given melanoma Ag involves a limited array of T cell clones
      bearing a structurally defined TCR. The aim of this study was to verify whether
      this information can be used to isolate and expand such anti-tumor effectors from
      fresh lymphocyte populations. We found that one to three different TCR beta-chain
      variable (TCRBV) regions were significantly expanded in 4-wk mixed lymphocyte
      tumor cultures (MLTC) from six HLA-A*0201+ melanoma patients, and that the T
      cells expressing the expanded TCRBV regions were involved in HLA class I
      restricted lysis of the tumor. T cell activation by mAbs to MLTC-selected TCRBV
      region and CD28 resulted in large scale expansion (1-10 x 10(9) cells) of T cell
      lines, highly enriched for the expression of a single TCRBV region and for CD8+ T
      cells. The TCRBV-driven selection was equally effective when applied to patients'
      or healthy donors' lymphocytes, and the T cell lines isolated from melanoma
      patients exerted HLA class I-restricted lysis of the autologous tumor. MLTC and
      TCRBV-selected lines recognized allogeneic melanomas sharing HLA-A and -B alleles
      with the autologous tumor, but only two of the HLA-A2-restricted lines were
      directed to a known peptide from melanoma-associated Ags. Single-strand
      conformation polymorphism analysis indicated a polyclonal composition of both
      MLTC and TCRBV-selected lines, but expansion of clonotypes with identical CDR3
      length was observed only in the MLTC lines. Thus, TCRBV-driven selection can be
      exploited to obtain large scale expansion of antitumor CTL lines from melanoma
      patients.

PMID- 9190944
TI  - B7-2 requirement for helminth-induced granuloma formation and CD4 type 2 T helper
      cell cytokine expression.
AB  - B7 ligands on APCs engage CD28/CTLA4 counter-receptors on T cells critical for T
      lymphocyte activation and functional differentiation of T helper subsets. To
      examine whether the ligands B7-1 (CD80) and B7-2 (CD86) affect gene expression of
      Th2 cytokines and development of Th2-mediated pathologic tissue reactions, mice
      were treated with anti-B7-1 or anti-B7-2 at the time of sensitization to footpad
      inoculation of Schistosoma mansoni eggs or induction of pulmonary granuloma by
      i.v. injected eggs. Anti-B7-2 treatment inhibited pulmonary granuloma formation
      by 74% and decreased levels of lung IL-5 and IL-13 transcripts compared with
      those in animals given control Ig by 20- and 5-fold, respectively, while anti-B7
      1 administration has no effect. Anti-B7-2 treatment blocked CD4 cell gene
      expression of IL-4, IL-5, and IL-13, but had no effect on IFN-gamma or IL-10 in
      animals inoculated with S. mansoni ova, larvae from the filarial helminth Brugia
      malayi, or CFA. Anti-B7-1 administration had no effect on CD4 cell transcript
      levels of IL-4 and IL-5, but inhibited IFN-gamma in mice inoculated with ova.
      Similar effects of anti-B7-2 on CD4 cell cytokine expression were observed in IL
      4 knockout mice, indicating the existence of an alternative pathway for induction
      and/or expression of these cytokine genes. These findings suggest a possible role
      for anti-B7-2 in the therapy of infectious and atopic diseases in which
      immunopathologic reactions are mediated by selected Th2 cytokines.

PMID- 9190945
TI  - Functions and specificity of T cells following nucleic acid vaccination of mice
      against Mycobacterium tuberculosis infection.
AB  - The 38-kDa glycolipoprotein of Mycobacterium tuberculosis has been known to evoke
      prominent T cell and Ab responses in patients with active tuberculosis. In this
      study, we investigated its protective capacity using plasmid DNA immunization in
      a mouse experimental model. Prior knowledge of several antigenic determinants has
      been beneficial for analyzing the phenotype and specificity of T cells, which
      determine the efficacy of this vaccination procedure. C57BL/6 mice responded to
      the 38-kDa gene-pcDNA3 plasmid with strong CD4+ Th1 and CD8+ cytotoxic T cell
      responses of the IFN-gamma-producing Tc1 phenotype. After challenge with virulent
      tubercle bacilli, the bacterial load in the spleens and lungs of vaccinated mice
      was reduced to a level similar to that imparted by Mycobacterium bovis Bacille
      Calmette-Guerin vaccination. Notably, the specificity of CD4+ and CD8+ T cells
      from DNA-vaccinated and tubercle-infected mice was found to be strikingly
      different in respect of several peptide epitopes. The identified peptides
      recognized by T cells from protected mice are of further interest for the
      development of subunit-based vaccines against tuberculosis.

PMID- 9190946
TI  - The differential ability of IL-8 and neutrophil-activating peptide-2 to induce
      attenuation of chemotaxis is mediated by their divergent capabilities to
      phosphorylate CXCR2 (IL-8 receptor B).
AB  - IL-8 and neutrophil-activating peptide-2 (NAP-2) are two closely related C-X-C
      chemokines that differ in their abilities to induce chemotaxis of human
      polymorphonuclear leukocytes (PMN). Although two IL-8R types are expressed by
      PMN, only CXCR2 binds NAP-2 and IL-8 with equally high affinity. By using
      enriched CXCR2-transfected 293 cells, we show that high doses of IL-8 induce
      attenuation of chemotaxis, while equivalent doses of NAP-2 do not.
      Phosphorylation analysis shows that IL-8 induces higher levels of phosphorylation
      of the carboxyl terminus of CXCR2 than does NAP-2, suggesting that the level of
      phosphorylation contributes to the ability of the chemokines to attenuate the
      chemotactic response. To directly evaluate this difference, we analyzed the
      ability of receptors mutated to delete regions that highly express potential
      phosphorylation sites to be phosphorylated and to mediate chemotactic
      attenuation. We found that a carboxyl terminus-truncated mutant of CXCR2 was not
      phosphorylated by high doses of IL-8, as determined by in vivo phosphorylation
      assays and by analysis of the electrophoretic mobility of the receptors on SDS
      PAGE gels. This mutated receptor had a significantly lower ability to attenuate
      IL-8-induced chemotaxis, indicating that the attenuation of chemotaxis is
      mediated by chemokine-induced receptor phosphorylation. In conclusion, the data
      show that the greater ability of IL-8 to induce receptor phosphorylation
      contributes to its more potent attenuation of chemotaxis as compared with NAP-2.
      This differential phosphorylation by IL-8 and NAP-2 of CXCR2 provides a basis for
      the divergent outcome of PMN-induced inflammation in response to these two
      closely related C-X-C chemokines.

PMID- 9190947
TI  - Impaired activation of nuclear factor-kappaB in endotoxin-tolerant rats is
      associated with down-regulation of chemokine gene expression and inhibition of
      neutrophilic lung inflammation.
AB  - We postulated that repeated injections of endotoxin could induce a state of
      endotoxin tolerance in rats that is mediated at least partially through a nuclear
      factor (NF)-kappaB-dependent mechanism. We treated rats with four doses of
      endotoxin (0.06 or 0.6 mg/kg/day) and evaluated the ability of these treatments
      to modulate activation of the transcription factor NF-kappaB induced by treatment
      with high dose endotoxin (6 mg/kg). In lung tissue, NF-kappaB activation in
      response to i.p. injection of high dose endotoxin was blocked by treatment with
      four daily doses of endotoxin at 0.6 mg/kg/day. Endotoxin tolerance in rats was
      associated with diminished endotoxin-induced mRNA expression of the NF-kappaB
      dependent rat chemokine, cytokine-induced neutrophil chemoattractant. Treatment
      of rats with four daily doses of 0.6 mg/kg/day of endotoxin almost completely
      abolished the neutrophilic alveolitis that occurs in rats following i.p.
      injection of high dose endotoxin. These data indicate that in vivo tolerance to
      endotoxin challenge is associated with and possibly mediated by inhibition of NF
      kappaB activation. Potentially, endotoxin tolerance could be exploited to limit
      inflammation in disease states whose pathobiology is related to excessive or
      unregulated inflammation.

PMID- 9190948
TI  - Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and
      its role in the pathophysiology of neutrophil-induced liver injury in murine
      endotoxin shock.
AB  - Polymorphonuclear leukocytes (neutrophils) can cause hepatic parenchymal cell
      injury during endotoxin (ET) shock. Because adhesion molecules are critical for
      inflammatory cell damage, the role of vascular cell adhesion molecule-1 (VCAM-1)
      was studied in the pathophysiology of ET shock. ET-sensitive mice (C3Heb/FeJ)
      were treated with 700 mg/kg galactosamine in combination with 100 microg/kg
      Salmonella abortus equi ET, 15 microg/kg TNF-alpha, or 13 to 23 microg/kg IL-1.
      VCAM-1 mRNA formation was strongly activated in animals treated with ET, TNF
      alpha, or IL-1. In contrast, only TNF-alpha and IL-1, not ET, induced VCAM-1 gene
      transcription in livers of ET-resistant mice (C3H/HeJ). Immunohistochemistry and
      isolation of liver cells during endotoxemia indicated that VCAM-1 mRNA and
      protein were only formed in endothelial cells and Kupffer cells, not in
      hepatocytes. Galactosamine/ET induced neutrophil accumulation in sinusoids (515
      +/- 30 neutrophils/50 high power fields) followed by transmigration at 7 h. At
      that time, severe liver injury was observed (necrosis, 53 +/- 5%). An anti-VCAM-1
      Ab (3 mg/kg) attenuated the area of necrosis by 60%. The Ab reduced neutrophil
      transmigration by 84%, but had no effect on the total number of cells in the
      liver vasculature. Flow cytometric analysis identified the presence of very late
      Ag-4 on mouse peripheral neutrophils. Our data demonstrated cytokine-dependent
      VCAM-1 gene transcription and protein expression in the liver during endotoxemia.
      Neutrophils were able to use very late Ag-4/VCAM-1 interactions to transmigrate
      into liver parenchyma in vivo. Preventing transmigration by blocking VCAM-1
      protected hepatocytes against neutrophil-induced injury.

PMID- 9190949
TI  - Extracellular release of the type I intracellular IL-1 receptor antagonist from
      human airway epithelial cells: differential effects of IL-4, IL-13, IFN-gamma,
      and corticosteroids.
AB  - Three IL-1R antagonists (IL-1Ra) exist: secreted IL-1Ra and intracellular IL-1Ra
      (icIL-1Ra) types I and II. We have previously reported that human airway
      epithelial cells (HAEC) express icIL-1Ra type I, which can be up-regulated by
      corticosteroids. This study assessed whether cytokines and corticosteroids
      differentially effect icIL-1Ra type I protein release from HAEC to the
      extracellular compartment. We report that icIL-1Ra type I mRNA and intracellular
      protein are up-regulated in NCI-H292 cells, a human pulmonary mucoepidermoid
      carcinoma cell line, in response to IL-4, IL-13, IFN-gamma, and dexamethasone.
      The icIL-1Ra type I protein was detected in concentrated cell culture
      supernatants from NCI-H292 cells and normal human bronchial epithelial cells. The
      release of biologically relevant concentrations of active IL-1Ra from normal
      human bronchial epithelial cells was demonstrated by the ability of a
      neutralizing anti-IL-1Ra Ab to augment IL-1beta-mediated IL-8 secretion. IL-4, IL
      13, and IFN-gamma induced immunoreactive IL-1Ra release into supernatants from
      NCI-H292 cells. Dexamethasone inhibited constitutive and cytokine-induced release
      of immunoreactive IL-1Ra. The release of icIL-1Ra type I protein was not related
      to cytotoxicity, as measured by lactate dehydrogenase. We propose that icIL-1Ra
      type I release from HAEC represents a novel mechanism by which IL-1 bioactivity
      in the airway microenvironment may be modulated. Cytokine-mediated icIL-1Ra type
      I synthesis may increase both intracellular protein and release to the
      extracellular space, where cell surface IL-1R can be antagonized. In contrast,
      corticosteroid-induced increases in icIL-1Ra type I synthesis and inhibition of
      extracellular protein release promote accumulation of icIL-1Ra type I protein
      within the intracellular compartment.

PMID- 9190950
TI  - Contribution of the complement control protein modules of C2 in C4b binding
      assessed by analysis of C2/factor B chimeras.
AB  - To identify the complement control protein (CCP) module(s) of C2 that are
      required for C4b recognition, we constructed a panel of C2/factor B chimeras by
      substituting intact or partial factor B CCP modules for the corresponding ones of
      C2. Epitope mapping indicated that the anti-C2b mAb 3A3.3, which inhibits binding
      of C2 to C4b, reacts with the second CCP of C2 and similarly the anti-Ba mAb HA4
      1A, which inhibits binding of factor B to C3b, reacts with the second CCP of
      factor B. The hemolytic activity of the chimeras CP1, CP2, and CP3a containing
      CCP1, CCP2, and a fragment of CCP3 of factor B, respectively, was substantially
      decreased compared with that of wild-type C2. The CP3 and CP1-3 chimeras, in
      which CCP3 and all three CCP modules of factor B, respectively, were substituted,
      had no hemolytic activity. Loss of activity could be attributed to the resistance
      of these two chimeras to C1s cleavage, which was probably due to conformational
      changes of the cleavage site. The combined results indicate that all three CCP
      modules of C2 contribute structural elements to the C4b-binding site of C2b. This
      site has been shown previously to be necessary for the initial binding of C2 to
      C4b which leads to the formation of the classical pathway C3 convertase.

PMID- 9190951
TI  - Transendothelial migration of lymphocytes from HIV-1-infected donors: a mechanism
      for extravascular dissemination of HIV-1.
AB  - To identify factors that cause HIV-1 to establish perivascular foci of infected
      cells, we studied the transendothelial migration of blood mononuclear leukocytes
      (MNL) from 76 HIV+ patients and 41 controls. The fraction of patients'
      lymphocytes that migrated across endothelial cell monolayers in vitro was
      significantly increased (p < or = 0.03) compared with that of control donors.
      Migration of patients' CD4+ T cells was particularly enhanced, whereas the
      migration of monocytes did not differ between patients and controls. Lymphocyte
      migration correlated with expression of CD11a/CD18 and CD49d/CD29 and with the
      quantity of TNF-alpha produced as MNLs migrated through the endothelium.
      Measurement of HIV-1 proviral DNA copies in the patients' MNLs (n = 26) suggested
      that in half the cases virus-infected cells accumulated preferentially amidst the
      migratory leukocytes. We observed the same behavior with normal donor MNLs
      infected, in vitro, with each of 4 strains of HIV-1. The number of HIV-1 proviral
      DNA copies per million MNLs was 40 to 178 times higher in the migratory
      population than in the original population added to the endothelium. To test
      whether only certain strains of HIV-1 stimulate transendothelial migration of
      infected cells, we used single strand conformation polymorphism analysis to
      identify quasispecies of HIV-1 in the MNLs. If all strains of HIV-1 were equal in
      their ability to stimulate transendothelial migration, we expected to find no
      differences in the quasispecies present in the original and migratory cell
      populations. In fact the quasispecies differed in 14 of 19 paired samples,
      suggesting that only certain HIV-1 quasispecies promote transendothelial
      migration of infected cells.

PMID- 9190952
TI  - IL-15 enhances immune functions during HIV infection.
AB  - IL-15, a new cytokine primarily produced by macrophages, has been shown to
      exhibit several functional properties shared with IL-2. Treatment of PBMC from
      HIV-infected patients with IL-15 resulted in an increase in NK cell cytotoxicity
      to levels similar to those of untreated PBMC from healthy donors. This effect is
      independent of several well-characterized regulatory cytokines, as it is not
      prevented by Abs that neutralize IFNs, TNF-alpha, IL-2, or IL-12. Enhanced
      cytotoxicity was accompanied by a significant increase in expression of cytotoxic
      granules. IL-15 enhanced the proliferative ability in both controls and HIV
      seropositive in response to mitogen and recall Ags. Although the addition of IL
      15 has a preventive effect on the appearance of spontaneous cell death, this
      effect was not seen during mitogen-induced apoptosis. The production of IL-15 by
      PBMC from patients in response to Staphylococcus aureus Cowan strain 1 appeared
      heterogeneous and was not negatively regulated by cytokines that inhibited IL-12
      production. No correlation was found between in vitro HIV infection and IL-15
      production, as viral infection had no effect on the ability of monocytes to
      produce IL-15 in response to S. aureus. Interestingly IL-15 restored the
      deficient production of IL-12 by PBMC from HIV+ people and had no major effect on
      modulating viral expression in latently infected cell lines or PBMC from
      naturally infected people. Taken together, these results suggest a potent
      immunoregulatory role of IL-15 during HIV infection.

PMID- 9190953
TI  - Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic
      mice.
AB  - We previously demonstrated that increased Fas expression in T cells of aged CD2
      fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T
      cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the
      average life span of Fas-Tg mice is comparable with that of nontransgenic (non
      Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of
      the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas
      no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition
      was observed primarily in glomeruli by using immunohistochemical stains and
      electron microscopy. The full-length amino acid coding sequence of serum amyloid
      A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible
      BALB/c mice. Although there was no significant difference in steady-state serum
      amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice
      with staphylococcal enterotoxin B resulted in significantly higher serum levels
      of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of
      weight loss on day 7 in aged Fas-Tg mice compared with young mice. These
      parameters, at the indicated time points, were equivalent between young and aged
      non-Tg mice. Taken together, our data suggest that prevention of T cell
      senescence in Fas-Tg mice may be a factor in induction of an excessive acute
      phase response triggered by T cell activation. The Fas-Tg mice are a novel model
      for understanding the immunologic mechanisms leading to secondary amyloidosis.

PMID- 9190954
TI  - IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context
      of a deviant effector response.
AB  - Experimental autoimmune uveitis (EAU) is a T cell-mediated disease that targets
      the neural retina and serves as a model of human uveitis. Uveitogenic effector T
      cells have a Th1-like phenotype (high IFN-gamma, low IL-4), and genetic
      susceptibility to EAU is associated with an elevated Th1 response. Here we
      investigate whether the ability to produce IFN-gamma is necessary for the
      development of EAU by immunizing IFN-gamma-deficient (GKO) mice with the
      uveitogenic protein interphotoreceptor retinoid binding protein (IRBP) and
      characterize the associated immunologic responses. GKO mice developed EAU
      comparable in severity and incidence to that of their wild-type littermates.
      However, the cytokine profile in their uveitic eyes as well as the cytokines
      produced by primed lymph node cells in response to IRBP showed a distinct
      profile: undiminished TNF-alpha and elevated IL-5, IL-6, IL-10, and lymphotoxin
      (but not IL-4) responses. The inflammatory infiltrate in GKO eyes contained an
      excess of granulocytes and IL-5- and IL-6-producing cells, but uveitic GKO mice
      did not up-regulate inducible nitric oxide synthase. GKOs had enhanced lymphocyte
      proliferation and delayed-type hypersensitivity responses to IRBP. Histology of
      the delayed-type hypersensitivity lesion in GKO had superimposed elements of an
      allergic-like response. Anti-IRBP Ab isotypes of GKO mice showed a reduction of
      IgG2a, but no enhancement of IgG1. Comparison of responses in +/+ and +/- wild
      type mice revealed some limited evidence of a gene-dose effect. We conclude that
      IFN-gamma is not required for priming of pathogenic T cells or for effecting the
      retinal damage and photoreceptor loss typical of EAU. However, what appears to be
      a grossly similar disease is caused in the GKO by a deviant type of effector
      response.

PMID- 9190955
TI  - Experimental autoimmune myasthenia gravis in B10.BV8S2 transgenic mice:
      preferential usage of TCRAV1 gene by lymphocytes responding to acetylcholine
      receptor.
AB  - Multiple TCRBV genes have been implicated in experimental autoimmune myasthenia
      gravis (EAMG) pathogenesis in susceptible H-2(b) strains of mice. We studied the
      contribution of specific TCRBV and AV genes in EAMG pathogenesis using B10.BV8S2
      transgenic mice (H-2[b]). The TCR transgenic mice predominantly have TCRBV8S2
      transgene, but can use any of the endogenous AV gene repertoire. The transgenic
      mice were immunized with acetylcholine receptor (AChR) in CFA and evaluated for
      EAMG pathogenesis. Although the lymphocyte responses to AChR in B10.BV8S2
      transgenic and nontransgenic TCR wild-type mice were equivalent, a marked
      reduction in lymphocyte response to the dominant AChR alpha chain peptide 146-162
      was observed in the TCR transgenic mice. After boosting with AChR in CFA, anti
      AChR Abs were detected in the serum, and 14 of 42 (33%) of the TCR transgenic
      mice developed clinical EAMG. Furthermore, EAMG in TCR transgenic mice was
      prevented by treatment with mAb to TCRBV8, which depleted BV8-expressing T cells.
      Cloning and sequencing of TCRAV genes from AChR-reactive T cells from B10.BV8S2
      transgenic mice revealed a pattern of restricted TCRAV gene usage. The majority
      (60%) of the clones sequenced showed a sequence identical with that of the
      TCRAV1S8 gene. In the normal spleen cells of TCR transgenic mice, AV gene usage
      was more random. Thus, despite the presence of a complete endogenous TCRAV
      repertoire in B10.BV8S2 transgenic mice, T cells responding to AChR
      preferentially used a single endogenous TCRAV gene, thus implicating the
      involvement of the TCRAV1S8 gene in EAMG pathogenesis.

PMID- 9190957
TI  - Functional dissection of systemic lupus erythematosus using congenic mouse
      strains.
AB  - We describe the in vivo phenotypes associated with three genomic intervals
      containing systemic lupus erythematosus (SLE)-susceptibility genes derived from
      the SLE-prone NZM2410 strain on a C57BL/6 genome. These intervals were identified
      previously via a genome-wide analysis of SLE susceptibility in a (NZM2410 x
      C57BL/6)F1 x NZM2410 backcross, and transferred independently on a C57BL/6
      background to produce three congenic strains: B6.NZMc1 carrying Sle1, B6.NZMc4
      carrying Sle2, and B6.NZMc7 carrying Sle3. B6.NZMc1 develops high titers of IgG
      anti-nuclear autoantibodies in the absence of any severe nephritis. B6.NZMc4
      spontaneously develops elevated levels of IgM, but not IgG Abs against several
      Ags, indicative of polyclonal activation or polyreactivity affecting the B cell
      lineage. B6.NZMc7 causes the production of IgM and IgG Abs against both nuclear
      and non-nuclear Ags and the development of severe lupus nephritis. Therefore, our
      results show that three defined genomic intervals from the NZM2410 SLE-prone
      strain each contribute specific component phenotypes that have been associated
      with SLE, which in combination can mediate severe disease.

PMID- 9190956
TI  - Restricted TCR V alpha repertoire in the T cell response to a tolerogenic
      determinant of type II collagen.
AB  - Tolerization of B10.RIII mice (H-2r) with i.v.-injected type II collagen (CII)
      renders the animals resistant to induction of collagen-induced arthritis (CIA).
      The B10.RIII mouse is of particular interest, in that the T cell determinants
      that induce tolerance are different from those that induce arthritis. To
      characterize T cells that react with the tolerogenic determinant and play a role
      in regulation of arthritis, we have developed a panel of T cell hybridomas
      reactive with the tolerogenic T cell epitope, CII 607-621. None of the hybrids
      cross-reacted with either the arthritogenic CII 445-453 or murine CII. As
      determined by PCR and immunofluorescence, the T cell response to the tolerogenic
      determinant was oligoclonal, with evident preferential usage of V alpha. Through
      the analysis of a large panel of T cell hybridomas, preferential usage of V
      alpha2, J alpha44, J beta2.7, and D beta2.1 was observed. Characterization of T
      cells reactive with the immunodominant determinant, CII 607-621, responsible for
      the induction of tolerance should prove important in developing novel therapeutic
      approaches for the treatment of autoimmune diseases.

PMID- 9190959
TI  - How should we monitor women treated for endometrial carcinoma?

PMID- 9190958
TI  - Diminished HIV-specific CTL activity is associated with lower type 1 and enhanced
      type 2 responses to HIV-specific peptides during perinatal HIV infection.
AB  - The early development of symptoms and the rapid progression of disease in some
      vertically infected infants are thought to reflect in part the immaturity of
      their immune systems. We examined the relationship between HIV-specific CTL
      activity and the profile of cytokine production induced by mAb to CD3 and HIV
      envelope (env) peptides P18 and T1 in PBMC derived from 0.6- to 3.6-yr-old
      children with perinatal HIV infection. Cellular immunity against HIV was
      demonstrated only during early stages of disease, whereas the responses were
      either undetectable or at background levels in HIV-infected children with rapidly
      progressing disease and in uninfected children of HIV+ and HIV- mothers. Levels
      of IL-2 mRNA in anti-CD3 mAb- and env peptide-induced PBMC varied and were
      increased in the infected children with high frequencies of HIV-specific CTL
      precursors. Analysis of IFN-gamma and IL-4 production by CD4+ T cell clones
      obtained from cultures stimulated with anti-CD3 mAb or the env peptides showed an
      increased proportion of Th2 and Th0 clones in HIV-infected children with lower
      HIV-specific CTL activity, whereas children with high CTL activity had increased
      numbers of Th1 clones. The results of these studies suggest that decreases in CTL
      activity to the virus might be associated with the induction of a type 2 cytokine
      response. These findings underline the role of cytokines in the generation of HIV
      specific CTL responses and may be important for the development of
      immunomodulatory and vaccine strategies to interrupt vertical transmission of
      HIV.

PMID- 9190960
TI  - Risk-specific follow-up for endometrial carcinoma patients.
AB  - OBJECTIVE: To propose a risk-specific follow-up protocol for endometrial
      carcinoma patients. METHODS: A retrospective cohort of endometrial carcinoma
      patients was used to identify risk factors for recurrence. Based on a profile of
      risk factors, women were classified at either low or high risk for recurrence
      (median follow-up 70 months). The classification system was validated on a
      subsequent cohort. RESULTS: Surgical stage, grade, and histology were found to be
      significant predictors (P < 0.001) of recurrence. In the original cohort,
      patients with stage Ia, grade 1 or 2, or stage Ib, grade 1 adenocarcinoma, had a
      recurrence rate of 4/98 (4.1%). The remaining high-risk patients had a recurrence
      rate of 37/158 (23.4%). When applied to the subsequent cohort, the rates were
      similar: low risk 3/113 (2.7%) and high risk 30/140 (21.4%). Seventy-five percent
      of recurrences occurred within 3 years of diagnosis and the majority were
      heralded by site-specific symptoms. CONCLUSIONS: Women with endometrial carcinoma
      can be successfully classified for low or high risk of recurrence. It is proposed
      that low-risk patients not be maintained on routine follow-up and that a tailored
      schedule of follow-up be used for high-risk patients. These changes would serve
      patients more appropriately and use health care resources more efficiently.

PMID- 9190961
TI  - Prospective study to compare endometrial cytology and transvaginal
      ultrasonography for identification of endometrial malignancies.
AB  - We compared transvaginal ultrasonography (TVS) and endometrial cytology by the
      Endocyte method for endometrial cancer screening. A total of 600 postmenopausal
      women who hoped for endometrial cancer screening (mean age, 61.1 +/- 8.8 years;
      range, 44-87 years) underwent TVS, endometrial cytology (Endocyte method), and
      endometrial histology. The endometrial borders could be visualized by TVS in all
      women studied. However, cytology could not be performed in 59 women (9.8%) due to
      cervical stenosis. These 59 women were excluded from further study. Of the 541
      remaining women, 38 had pathologic conditions (16 had endometrial cancer and 22
      had endometrial hyperplasia). One (6.3%) of the 16 endometrial cancer patients
      and 10 (45.5%) of the 22 hyperplasia patients were asymptomatic. One hundred
      thirty-nine (83.7%) of the 166 women with postmenopausal bleeding had no
      pathological condition. When the cutoff value of endometrial thickness was set at
      4 mm for women <5 years since menopause and 3 mm for those > or =5 years since
      menopause, TVS showed a 97.4% sensitivity, 75.7% specificity, 23.8% positive
      predictive value, and 99.7% negative predictive value. Thirty-seven of the 38
      patients with endometrial disease were detected by TVS. Eight patients with a
      benign Endocyte examination were found to have endometrial hyperplasia. However,
      all endometrial cancers were detected by cytological examination. The Endocyte
      method exhibited 78.9% sensitivity, 95.4% specificity, 56.6% positive predictive
      value, and an 88.5% negative predictive value. In conclusion, TVS is thought to
      be useful for identification of patients who required further diagnostic
      investigation including endometrial histology.

PMID- 9190962
TI  - Loss of heterozygosity at the alpha-inhibin locus on chromosome 2q is not a
      feature of human granulosa cell tumors.
AB  - The alpha-inhibin gene has been shown in knockout mouse models to be a suppressor
      of granulosa tumorigenesis in the mouse. To determine if alpha-inhibin has the
      same function in humans, we have assessed the frequency of loss of heterozygosity
      (LOH) of the alpha-inhibin gene locus on chromosome 2q in 17 human granulosa cell
      tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%)
      epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data
      suggest that in contrast to the suggestions from the mouse model alpha-inhibin
      does not function as a granulosa cell tumor suppressor gene in the human.
      Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to
      detect either LOH or point mutations, indicating that they have a developmental
      pathway distinct from that of epithelial ovarian tumors.

PMID- 9190963
TI  - Tumor lymphocytes in patients with advanced ovarian cancer: changes during in
      vitro culture and implications for immunotherapy.
AB  - Tumor specimens and ascites of patients with advanced ovarian cancer were
      utilized to obtain both primary ovarian carcinoma cell cultures and lymphocytes:
      tumor-infiltrating lymphocytes (TILs) from solid tumor tissue and tumor
      associated lymphocytes (TALs) from peritoneal fluid. Tumor lymphocytes were grown
      in coculture with autologous tumor cells and recombinant human IL-2 (rhIL-2) for
      up to 4 weeks and at weekly intervals these were examined with respect to
      phenotype and cytotoxicity. The phenotype was studied using flow cytometry for a
      variety of human immunocompetent cell surface markers (CD3, CD4 CD8, CD16, CD56,
      TCR alphabeta, TCRgammadelta). Cytotoxicity was investigated using 4-hr 51Cr
      release assays with the primary ovarian carcinoma cell cultures and the K562 cell
      line as target cells. The tumor lymphocytes did not demonstrate any obvious trend
      in phenotype changes during culture, although for different cultures a large
      range was noted for the various lymphocyte populations studied. Cytotoxicity
      against both autologous and allogeneic targets declined with culture length for
      the majority (6/7) of the lymphocyte cell lines tested (greatest at 1 week and
      least at 3 weeks). These initial results indicate that an in vitro non-MHC
      restricted cytotoxic function of peritoneal lymphocytes can be effectively
      activated with IL-2 and autologous tumor cells. However, if activated lymphocytes
      are to be employed as a form of immunotherapy, they should be given within the
      first week of culture for maximum cytotoxic effect.

PMID- 9190964
TI  - Different detectability of high-risk HPV in smears from incident and prevalent
      high-grade squamous intraepithelial lesions of the cervix.
AB  - Human papillomavirus (HPV) status in cervical smears from cervical
      intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history
      of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in
      40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all
      patients cervical smears for HPV testing and cytology and two cervigrams were
      taken. The scrapes were collected in hybrid capture assay solution and analyzed
      with the hybrid capture and general primer/type-specific primer polymerase chain
      reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and
      prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out
      under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4%
      (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in
      prevalent CIN 2/3 (P = 0.003). Using hybrid capture, smears of incident CIN 2/3
      were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN
      2/3 (P = 0.006). High-risk HPVs were significantly less common in smears from
      incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P
      = 0.001) and 47.2% vs 80% by hybrid capture assay (P = 0.003), respectively.
      Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher
      than of incident CIN 2/3 using semiquantitative PCR (P = 0.0005). Thus, high-risk
      HPV types were detected less frequently and in lower concentration in smears from
      incident CIN 2/3 than in smears from prevalent CIN 2/3.

PMID- 9190965
TI  - Use of the omental J-flap for prevention of postoperative complications following
      radical abdominal hysterectomy: report of 140 cases and literature review.
AB  - Over a 7-year period from 1989 to 1996, 140 patients had an omental J-flap placed
      following type III radical abdominal hysterectomy. There were no complications as
      a result of omentopexy, and postoperatively no patient developed urinary fistula,
      pelvic infection or abscess, or intestinal obstruction even in the 35 patients
      who received whole pelvic radiation therapy postoperatively. The omental J-flap
      is a rapid, effective means of minimizing surgical morbidity following radical
      abdominal hysterectomy and merits consideration for routine placement at the
      conclusion of radical abdominal hysterectomy.

PMID- 9190966
TI  - Transvaginal sonography as a screening method for the detection of early ovarian
      cancer.
AB  - From December 1987 to December 1993, 6470 women underwent screening with
      transvaginal sonography (TVS) as part of the University of Kentucky Ovarian
      Cancer Screening Project. Two groups of women were eligible to participate in
      this investigation: (i) asymptomatic postmenopausal patients or patients >50
      years of age, and (ii) asymptomatic women >30 years of age with a family history
      of ovarian cancer. Ovarian volume was calculated using the prolate ellipsoid
      formula (length x height x width x 0.523). An abnormal sonogram was defined by
      (1) an ovarian volume >10 cm3 in postmenopausal women or >20 cm3 in premenopausal
      women, and (2) a papillary or complex tissue projection into a cystic ovarian
      tumor. All women with an abnormal TVS had a repeat sonogram in 4-6 weeks.
      Patients with persistently abnormal scans had a serum CA-125 determination, tumor
      morphology indexing, and color Doppler sonography. Ninety patients (1.4%) with a
      persisting abnormality on TVS underwent exploratory laparotomy or laparoscopy for
      tumor removal. Thirty-seven patients had serous cystadenomas and six had primary
      ovarian cancers. Five patients had Stage IA ovarian cancer and one patient had
      Stage IIIB disease. Only one of the ovarian cancer patients had a palpable
      abnormality on pelvic examination, and none had an elevated (>35 u/ml) serum CA
      125. All these patients are presently alive and well 1-5 years after conventional
      therapy. There was one false negative in this study, a 38-year-old white female
      who was noted to have a small ovarian cancer at the time of laparoscopic
      prophylactic oophorectomy 11 months after a normal scan. Over 17,000 screening
      years have been accrued and there have been no deaths from primary ovarian cancer
      in the screened population. A cost analysis of TVS screening is presented.

PMID- 9190967
TI  - Intrauterine sonography for preoperative assessment of cervical invasion in
      endometrial carcinoma.
AB  - Cervical involvement is one of the major prognostic factors in carcinoma of the
      endometrium confined to the uterus. The purpose of this study was to determine
      whether intrauterine ultrasound with a high-frequency miniature probe can depict
      the degree of cervical involvement of the disease. Thirty-two women with
      endometrial carcinoma underwent preoperative transvaginal and intrauterine
      sonography. By both scans, the degree of cervical involvement was prospectively
      evaluated. Sonograms were compared with the findings from histologic examination.
      Intrauterine sonography was completed in 30 of the 32 patients. In these 30
      patients, the degree of cervical involvement (none, endocervical gland, or
      cervical stroma) based on transvaginal scan was correct in 23 cases (77%), and
      that based on intrauterine scan was correct in 26 cases (87%). Three tumors with
      endocervical glandular involvement were correctly diagnosed by intrauterine
      sonography, whereas they were incorrectly diagnosed by transvaginal scan. The
      specificity and positive predictive value of intrauterine sonography for the
      assessment of the presence of cervical stromal invasion are 100% (26/26 and 3/3,
      respectively). Although this study is preliminary, our experience with
      intrauterine sonography shows that it has potential for assessing cervical
      stromal invasion in endometrial carcinoma.

PMID- 9190968
TI  - Therapeutic value of neoadjuvant intra-arterial chemotherapy (cisplatin) and
      irradiation for locally advanced uterine cervical cancer.
AB  - We analyzed long-term treatment results in 51 patients with locally advanced
      uterine cervical carcinoma (IIB, 4; IIIB, 43; IVA, 4) treated with neoadjuvant
      intra-arterial (I-A) chemotherapy (cisplatin) via the uterine artery and
      irradiation. Thirty patients (58.8%) developed recurrence. Twelve had pelvic
      recurrence alone, 8 had distant metastases alone, and 10 had both pelvic and
      distant failure. The 5-year cumulative pelvic control rate, absolute survival
      rate, and disease-free survival rate were 55.3, 47.1, and 39.4%, respectively.
      Eight of 51 patients (15.7%) suffered late complications. These results suggest
      that our neoadjuvant I-A chemotherapy prior to irradiation has limited additional
      value for long-term prognosis in patients with locally advanced uterine cervical
      carcinoma.

PMID- 9190969
TI  - Epidermal growth factor receptor in vulvar malignancies and its relationship to
      metastasis and patient survival.
AB  - OBJECTIVE: To evaluate the level of epidermal growth factor receptor (EGF-R)
      expression in vulvar malignancies and to determine if a correlation exists
      between EGF-R levels and metastasis or patient survival. METHODS: All patients
      with a diagnosis of invasive squamous cell carcinoma of the vulva who were
      treated at our institution with a primary radical vulvectomy and inguinal lymph
      node dissection from 1983 to 1993 were eligible for the study. Sixty-one patients
      with available tissue blocks of benign vulvar epithelium, the primary malignant
      vulvar lesion, and groin node metastasis (when positive) were included in the
      study. Semiquantitative EGF-R expression was determined in a blinded fashion
      utilizing immunohistochemical staining of appropriate tissue samples. Survival
      was calculated utilizing Kaplan-Meier life table analysis based upon disease-free
      survival. RESULTS: A significant increase (P < 0.001) in mean EGF-R levels was
      demonstrated in the primary tumor (67%) versus benign vulvar epithelium (31%). In
      the 14 patients with lymph node metastasis, the mean EGF-R level in the primary
      tumor was 65% versus 88% in the metastatic lesion (P < 0.001). The likelihood of
      lymph node metastasis was elevated in those patients with a benign tissue EGF-R
      level > or =40% (P < 0.03) and in those patients with a primary tumor EGF-R level
      > or =90% (P < 0.025). Life table analysis revealed a cumulative disease-free
      survival of 45% for all patients. Disease-free survival in those patients with
      EGF-R levels > or =90% in the primary tumor was 25%, contrasting with a disease
      free survival of 54% in those patients with EGF-R levels <90% (P < 0.05).
      CONCLUSIONS: There is a progressive increase in EGF-R expression from benign
      vulvar epithelium to primary malignant tissue to metastatic lesions within the
      same patient. Increased expression of EGF-R in the primary vulvar malignancy is
      significantly associated with lymph node metastasis and decreased patient
      survival. Increased expression of EGF-R in histologically benign vulvar
      epithelium has a significant association with lymph node metastasis and may
      predict decreased patient survival.

PMID- 9190970
TI  - Histology/cytology discrepancies in HIV-infected obstetric patients with normal
      pap smears.
AB  - OBJECTIVE: To estimate the frequency of cervical cytologic/histologic
      discrepancies in a group of obstetric patients diagnosed as HIV infected by
      routine prenatal screening. Also, to determine if serum CD4 levels or sexually
      transmitted diseases (STDs) are associated with the occurrence of preinvasive
      cervical disease in these women. METHOD: Thirty-two women who presented for
      routine prenatal care to Medical Center of Louisiana were diagnosed as HIV
      infected by ELISA and Western blot testing and had normal Pap smears. These
      patients then agreed to undergo the following: colposcopy with directed biopsies;
      chlamydia, gonorrhea, and syphilis screening; and serum CD4 level. RESULTS: No
      patients had AIDS-defining diagnoses other than CD4 < 200/mm3. Ten of 32 (31%)
      had cervical intraepithelial neoplasia (CIN) despite normal cytology. Six of 32
      (19%) had STDs. One of 10 in the group with CIN had a STD. The mean CD4 level in
      those patients with CIN was 249/mm2 (range 1-524) vs 501/mm2 (range 210-979) in
      those without CIN. (P = 0.0118) CONCLUSIONS: Newly diagnosed HIV-infected
      pregnant women without clinical evidence of AIDS are noted to have CIN at a rate
      similar to nonpregnant HIV-infected women. The Pap smear appears to have a
      significant false-negative rate in this group. STDs, while common, were not
      directly associated with false-negative Pap smears. CIN is associated with
      immunosuppression, as measured by low CD4 counts.

PMID- 9190971
TI  - Continued chemosensitivity to cisplatin/carboplatin in ovarian carcinoma despite
      treatment with multiple prior platinum-based regimens.
AB  - While it is well recognized that individuals with ovarian cancer who have
      previously responded to platinum-based therapy can achieve a second response to
      cisplatin or carboplatin at the time of relapse, limited data exist in the
      oncologic literature regarding the number of times this process can be repeated.
      We briefly report here three patients with ovarian cancer currently being cared
      for in the Gynecologic Oncology program of the Cleveland Clinic Foundation who
      have achieved four (1 patient) or five (2 patients) separate clinical responses
      to cisplatin or carboplatin-based chemotherapy and have survived >4 years since
      the date of first relapse. This experience emphasizes the point that platinum
      resistance cannot be defined based on total treatment courses or the number of
      prior platinum-based regimens delivered, but only by objective evidence of
      failure of the drugs in an individual patient.

PMID- 9190972
TI  - Microinvasive carcinoma of the uterine cervix: histological findings on cone
      specimens related to residual neoplasia on hysterectomy.
AB  - The treatment of cervical microinvasive carcinoma is controversial. Hysterectomy
      is performed in almost all cases, associated or not with more radical procedures.
      Currently, there is a tendency to adopt conservative management to treat patients
      with early invasion, as long as it can be assured that the whole lesion has been
      removed. The aim of this study was to establish which histological information
      should be obtained from the cones that would give the best possible assurance of
      absence of residual neoplasia in the patient. This was done by comparing cone and
      hysterectomy specimens from each patient. One hundred sixty-three cases, treated
      from 1967 to 1994, underwent simple or radical hysterectomy following cone
      biopsy. We evaluated the following histological features in the cones: (i)
      invasion depth, (ii) lateral extension of the lesion, (iii) unifocal or extensive
      lesion, (iv) vascular invasion, (v) morphological signs of HPV infection, and
      (vi) free or involved cone surgical margins. Residual neoplasia in the
      hysterectomy was more frequent when the margins of the cone were involved by
      atypical epithelium, and in cases with signs of HPV infection. However, according
      to statistical analysis, these two variables were not mutually independent, and
      the only important parameter to predict residual neoplasia in the hysterectomy
      specimens was involved surgical margins in the cone.

PMID- 9190973
TI  - The frequency of human papillomavirus detection in postmenopausal women on
      hormone replacement therapy.
AB  - Postmenopausal women enrolled in the Iowa portion of the postmenopausal
      estrogen/progestin interventions randomized clinical trial (n = 105) during 1989
      1991 were studied for (i) the prevalence of human papillomavirus (HPV) in this
      older age population (ages 45-64), and (ii) the association between hormone
      replacement therapies (HRTs) and changes in detection of HPV over a 2-year time
      period. HPV is causative in most cervical and some other genital cancers and in
      the presence of steroid hormones has been shown to increase neoplastic
      transformation by HPV in vitro. Using PCR to detect HPV DNA, the overall
      frequency of the virus regardless of time period was 50.3% (n = 53) with a
      baseline (BL) frequency of 38.1% and the second year follow-up (FU) of 22.9%. The
      oncogenic types HPV-16 (75.5%) and HPV-31 (20.8%) were the most commonly
      reported. All those with persistently detected infection (10.5%), defined as HPV+
      at both BL and FU, were identified with HPV-16 or -18. Between these two time
      periods there were no significant differences in HPV frequency between the
      placebo and combined HRT groups (BL-/FU+, 21% vs 18%; BL+/FU-, 71% vs 80%). While
      the study is based on a small sample, the findings suggest that short-term use of
      HRTs is not associated with an increased risk of HPV detection, but assessment of
      effects from long-term use is needed. The data also indicate that the frequency
      of HPV found in older women is higher than previously suspected but that short
      term changes in HPV detected in this age group are unrelated to the development
      of precancerous cervical lesions.

PMID- 9190974
TI  - Juvenile granulosa cell tumors of the ovary in children and adolescents: results
      from 33 patients registered in a prospective cooperative study.
AB  - Clinical and pathological data from 33 prospective registered patients who
      suffered from juvenile granulosa cell tumors (JGCT) were evaluated according to
      treatment and outcome. The median age at the time of diagnosis was 7.6 years
      (range, 6 months to 17.5 years). Fourteen patients showed signs of a pseudo
      precocious puberty. In 1 patient premenarcheal bleeding was the only clinical
      symptom of the disease. A pelvic tumor or an abdominal distention was found in 6
      children, revealing signs of an acute abdomen in 3 children. Tumor staging was
      performed according to the FIGO (International Federation of Gynecology and
      Obstetrics) classification for ovarian tumors. Twenty children and adolescents
      were classified as FIGO stage Ia; 8 children had stage Ic tumors. In 4 patients
      stage IIc and in 1 patient stage IIIc tumors were observed. For local tumor
      control all 33 patients underwent tumor resection and oophorectomy, which was
      complete in 28 patients. Adjuvant combination chemotherapy was used in 1 girl who
      presented with high mitotic pathological index features in FIGO stage Ia. In 8
      other children between FIGO stage Ic and IIIc, treatment was also intensified by
      multidrug chemotherapy. After a follow-up period of 168 months, an event-free
      survival of 0.75 +/- 0.07 was observed. From our data we conclude that multidrug
      chemotherapy including cisplatin-based regimens may be useful to enhance
      treatment results of JGCT, especially in advanced FIGO stages.

PMID- 9190975
TI  - Long-term survival with whole abdominopelvic irradiation in platinum-refractory
      persistent or recurrent ovarian cancer.
AB  - The purpose of this study is to retrospectively evaluate the efficacy and
      toxicity of whole abdominopelvic irradiation (WAI) in patients with persistent or
      recurrent epithelial ovarian carcinoma who failed chemotherapy. Between 1970 and
      1995, 41 women with persistent or recurrent ovarian carcinoma after initial
      treatment with surgical debulking and chemotherapy (4 to 18 cycles; median, 8)
      were treated with WAI. Thirty-one patients had received platinum-based regimens,
      and 22 of these had failed within 6 months after completion of chemotherapy
      ("platinum-refractory"). Prior to WAI, 11 (27%) patients had microscopic residual
      disease, 21 (51%) had gross residual disease up to 1.5 cm, and 9 (22%) had
      residual tumors greater than 1.5 cm in maximal diameter. Median doses of 28 Gy to
      the abdomen and 48 Gy to the pelvis were delivered using open-field techniques
      and liver and kidney shielding. With follow-up of 1 month to 16.5 years (median
      potential follow-up, 1.4 years), the 5-year actuarial disease-specific survival
      was 47% in all 41 patients, and 50% in the 22 platinum-refractory patients. Both
      residual tumor size at WAI (P < 10(-4)) and initial stage (P = 0.003) were of
      prognostic value. Five-year disease-specific survival of all patients with
      residual tumors less than 1.5 cm was 53%; 0% for patients with tumors greater
      than 1.5 cm. Five-year disease-specific survivals by initial stage were: stage I
      and II, 75%; stage III, 40%; and stage IV, 15%. Stage I, II, or III patients with
      residual disease up to 1.5 cm before WAI had a 10-year actuarial disease-specific
      survival of 40%. Twelve patients (29%) failed to complete the planned course of
      WAI due to acute toxicity (most often due to prolonged thrombocytopenia). Late
      toxicity (requiring surgery) included bowel obstruction in two patients and
      fistula in one patient. Whole abdominopelvic irradiation should be considered in
      selected patients who fail initial chemotherapy, especially in patients who can
      or have been debulked to small amounts of residual disease. With acceptable
      toxicity, WAI results appear to be as good as or better than second-line
      chemotherapy, particularly in platinum-refractory patients.

PMID- 9190976
TI  - Erythropoietin treatment under polychemotherapy in patients with gynecologic
      malignancies: a prospective, randomized, double-blind placebo-controlled
      multicenter study.
AB  - In order to examine the influence of erythropoietin (rHuEPO) on serum hemoglobin
      levels, transfusion requirements, and quality of life in patients with
      gynecologic malignancies under polychemotherapy and chronic tumor anemia
      (hemoglobin <11 g/dl), we performed a prospective, randomized, double-blinded
      placebo-controlled clinical trial. Between October 1992 and October 1993, 35
      patients from 5 gynecologic departments were entered into this trial. Inclusion
      criteria were hemoglobin level <11 g/dl, ferritin level >29 ng/ml, stool negative
      for occult blood, and life expectancy for more than 3 months. Patients received
      either 150 U/kg body wt rHuEPO (Erypo by Cilag-Janssen) sc three times a week for
      12 weeks (n = 23) or a placebo (n = 12). If the hemoglobin levels of the 4th,
      8th, or 12th week were >2 g/dl above the baseline value and/or >12 g/dl, the
      patient was classified as a responder. Patients who required blood transfusions
      (hemoglobin <8 g/dl, erythrocytes <3 x 10(6)/ml, or clinical symptoms of anemia)
      were classified as nonresponders. A nonvalidated quality of life questionnaire
      was completed by the patient at the beginning of the treatment and then every
      fourth week before receiving chemotherapy. In the rHuEPO group 56.6% of the
      patients responded to the treatment (chi2 = 10.79, P = 0.001) and only 5 patients
      (21.7%) required blood transfusions, whereas 8 of 12 patients in the placebo
      group (66.6%) had to be transfused (chi2 = 6.81, P = 0.009). Quality of life did
      not differ significantly between the rHuEPO group and the placebo group of
      patients. Within the rHuEPO group those patients that responded showed a
      significant increase in physical activity after response in comparison to the
      preresponsive phase (P = 0.02, paired t test). We therefore concluded that rHuEPO
      significantly increases serum hemoglobin levels and decreases transfusions
      requirements while maintaining quality of life in patients with gynecological
      malignancies who are undergoing polychemotherapy.

PMID- 9190977
TI  - Significance of lymph node sampling in epithelial carcinoma of the ovary.
AB  - From 1979 to 1984, 127 patients operated on for ovarian cancer underwent pelvic,
      para-aortic, or pelvic and para-aortic lymph node sampling. Forty-seven patients
      proved to be stage I(14 IA and 33 IC), 14 were stage II(3 IIA, 8 IIB, and 3 IIC),
      58 were stage III (7 IIIA, 13 IIIB, and 38 IIIC), and 8 were stage IV. Positive
      lymph nodes were found in 4.2% of patients at stage I, 35.7% at stage II, 41.3%
      at stage III, and 87.5% at stage IV. With regard to grading, positive lymph nodes
      were found in 4.4% of G1, in 21.6% of G2, and in 49.1% of G3. A significant
      increase in survival (P = 0.04) was found for patients classified as stage IIIC
      only according to lymph node involvement compared to patients in peritoneal stage
      IIIC with positive lymph nodes (3-year survival: 46% vs 12%). A small increase in
      survival was observed for N- patients compared to N+ patients, at both stage III
      and IV, even with same residual tumor size, but the difference is not
      statistically significant. All other things being equal, because the prevalence
      of lymph node positivity depends closely on the number of lymph nodes removed and
      examined (OR = 3.9 for >10 lymph nodes removed compared to 1-5 lymph nodes
      removed), lymph node sampling does not seem to be a reliable method for
      evaluating the retroperitoneal status. With regard to the therapeutic role of
      systematic lymphadenectomy, few data in literature are available and, most
      important, are not derived from experimental studies. Probably, only randomized
      studies with a large number of patients will provide useful answers.

PMID- 9190978
TI  - Whole abdominal external beam radiation in the treatment of primary carcinoma of
      the fallopian tube.
AB  - Thirty-two patients with adenocarcinoma of the fallopian tube, treated between
      1975 and 1990, were studied. Thirteen patients had stage I disease, 9 stage II,
      and 10 stage III. All patients underwent bilateral salpingo-oophorectomy, total
      abdominal hysterectomy, and subcolic omentectomy. All patients received
      postoperative primary whole abdominal external beam radiotherapy. Seventeen
      patients (53.1%) of the treated group survived NED for at least 5 years. Survival
      was 76.9% for stage I, 55.6% for stage II, and 20% for stage III. In the Cox
      multivariate analysis, two variables were independently related to survival:
      stage of disease and size of residual disease after surgery. Postoperative
      teleradiotherapy was totally ineffective in gross residual (>2 cm in diameter)
      disease (0% 5-year NED survivors) and not effective enough in small residual
      disease (<2 cm in diameter) (33% 5-year NED survivors). Despite postoperative
      whole abdominal external beam radiotherapy, 3 patients with microscopic, 4 with
      small, and 4 with gross residual disease did fail within the peritoneal cavity.

PMID- 9190979
TI  - A randomized study comparing retroperitoneal drainage with no drainage after
      lymphadenectomy in gynecologic malignancies.
AB  - OBJECTIVE: To evaluate the clinical effectiveness of retroperitoneal drainage
      following lymphadenectomy in gynecologic surgery. METHODS: One hundred thirty
      seven consecutive patients undergoing systematic lymphadenectomy for gynecologic
      malignancies were randomized to receive (Group A, 68) or not (Group B, 69)
      retroperitoneal drainage. The pelvic peritoneum and the paracolic gutters were
      not sutured after node dissection. Perioperative data and complications were
      recorded. RESULTS: Clinical and surgical parameters were comparable in the two
      groups. Postoperative hospital stay was significantly shorter in Group B (P <
      0.001), whereas the complication rate was significantly higher in Group A (P =
      0.01). This was mainly due to a significant increase in lymphocyst and lymphocyst
      related morbidity. Sonographic monitoring for lymphocyst showed free abdominal
      fluid in 18% of drained and 36% of not-drained patients (P = 0.03). Symptomatic
      ascites developed in 2 drained (3%) and 3 not-drained (4%) patients (NS),
      respectively. CONCLUSIONS: Prophylactic drainage of the retroperitoneum seems to
      increase lymphadenectomy-related morbidity and postoperative stay. Therefore,
      routine drainage following lymphadenectomy seems to be no longer indicated when
      the retroperitoneum is left open.

PMID- 9190981
TI  - The role of whole-pelvic irradiation in the treatment of early-stage uterine
      carcinosarcoma.
AB  - Thirty-eight patients with Stage I and II uterine carcinosarcoma were treated by
      surgery with and without whole-pelvic irradiation (WPI) at our institution from
      1975 to 1993. Ten patients (8 Stage I and 2 Stage II) were treated with surgery
      alone, while 28 patients (20 Stage I and 8 Stage II) received WPI in addition to
      surgery. With a median follow-up of 75 months (range 25-220 months), a trend
      toward a decreased rate of pelvic recurrence in those receiving WPI (6/28, 21%)
      compared to those treated with surgery alone (5/10, 50%) was observed (P = 0.09).
      There was no difference in the rate of distant recurrence between those receiving
      WPI (12/28, 43%) and those who did not (4/10, 40%) (P = 0.9). There was also no
      difference in the 2- and 5-year Kaplan-Meier survival estimates for the patients
      receiving WPI (79 and 59%, respectively) compared to those who did not receive
      WPI (60 and 60%, respectively) (P = 0.84). In this small series, the addition of
      whole-pelvic irradiation to primary surgery did not improve survival; however, a
      trend toward improved pelvic control was observed, suggesting a possible benefit
      for pelvic irradiation that should be studied in future trials.

PMID- 9190980
TI  - Effects of beta-carotene and other factors on outcome of cervical dysplasia and
      human papillomavirus infection.
AB  - Women with histopathologically confirmed cervical intraepithelial neoplasia (CIN)
      were followed at 3-month intervals in a randomized double-blinded trial to
      evaluate the efficacy of beta-carotene to cause regression of CIN. Questionnaire
      data, plasma levels of micronutrients, and a cervicovaginal lavage for human
      papillomavirus (HPV) detection were obtained at each visit, and an endpoint
      biopsy was performed at 9 months. Sixty-nine subjects had a biopsy endpoint
      evaluation; 9 of 39 (23%) subjects in the beta-carotene group versus 14 of 30
      (47%) in the placebo group had regression of CIN (P = 0.039). Independent risk
      factors for persistent CIN at 9 months included type-specific persistent HPV
      infection (OR = 11.38, P = 0.006) and continual HPV infection with a high viral
      load (OR = 14.25, P = 0.007) at baseline and 9 months, an initial diagnosis of >
      or =CIN II (OR = 6.74, P = 0.016), and older age (OR for > or =25 years = 4.10, P
      = 0.072). After controlling for these factors, the beta-carotene and placebo
      groups did not differ in risk for having CIN at 9 months (OR = 1.53, P = 0.550).
      Resolution of baseline HPV infection was significantly correlated with non-high
      risk HPV types (RR = 2.94, P = 0.015), age <25 years (RR = 2.62, P = 0.014), and
      douching after sexual intercourse (RR = 3.02, P = 0.012), but not with
      randomization group. Our data indicate that a large proportion of mild CIN
      lesions regress; age and HPV infection play an important role in the natural
      course of CIN; and repeated HPV testing may have a value in distinguishing women
      who need aggressive treatment for CIN versus those who do not. Supplementation of
      beta-carotene does not appear to have a detectable benefit in treatment of CIN.

PMID- 9190983
TI  - Radiation therapy results for patients undergoing inappropriate surgery in the
      presence of invasive cervical carcinoma.
AB  - Total vaginal or abdominal hysterectomy was considered an inadequate treatment
      method for invasive uterine cervix cancer. Usually the procedure was
      inadvertently performed on patients who were thought preoperatively to have
      benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing
      hysterectomy in the presence of invasive cervical cancer were treated with
      external radiation therapy and/or intracavitary radiotherapy. Preoperative
      diagnoses were carcinoma in situ (36), severe dysplasia (2), and early invasive
      cancer (14), and others were benign disease. Overall 5-year survival and relapse
      free survival rates were 75.8 and 77.5%, respectively. For patients in
      retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5
      year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients
      developed treatment failure; most of them (10/13) were patients with gross
      residual disease. Patients with early invasive cervical cancer (stage IA) had no
      treatment-related failure. Prognostic factors affecting survival by univariate
      analysis were retrospective stage (P = 0.0000) and preoperative diagnosis (P =
      0.0021). Tumor histology was marginally significant factor (P = 0.0938). By
      multivariate analysis, only retrospective stage was significant prognostic factor
      (P = 0.0001). Adjuvant radiotherapy appears to be an effective treatment method
      for patients with presumed stage IA and IB after inadvertent hysterectomy.
      Survival for patients with gross disease remaining after inappropriate
      hysterectomy is poor. So, early cancer detection and proper management with
      precise pretreatment staging is necessary to avoid inadherent hysterectomy,
      especially in cases of gross residual disease.

PMID- 9190982
TI  - Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian
      cancer patients with minimal residual disease at second look: a prospective
      randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.
AB  - From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal
      (less than 2 cm) residual disease after platinum-based front-line chemotherapy
      and second-look laparotomy entered a cooperative randomized study aimed at
      evaluating the effectiveness and the toxicity of the addition of interferon
      alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were
      randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28
      days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin
      400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with
      interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and
      anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were
      significantly more frequent in the combination arm. No difference in
      gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up
      time of 13 months (range 1-72) 71 patients showed a disease progression (31
      CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median
      progression-free survival was 11 months in the CBDCA group and 10 months in the
      CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN
      arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem
      to improve the results achievable with intraperitoneal carboplatin in this subset
      of patients, while the toxicity and the costs of the combination are consistently
      higher than with chemotherapy alone.

PMID- 9190984
TI  - Multiple immunoreactive inhibin proteins in serum from postmenopausal women with
      epithelial ovarian cancer.
AB  - Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be
      elevated in serum of women with ovarian cancer. However, inhibin is secreted in
      multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin
      precursors (pro-alphaC), each of which can now be specifically measured. We have
      examined the secretion of inhibin B and pro-alphaC inhibin in serum from women
      with epithelial ovarian cancer (EOC) for the first time, and have compared these
      analytes to inhibin A and total inhibin (inhibin A + B + pro-alphaC) as potential
      serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin
      proteins studied, the best serum marker was pro-alphaC, with 22% of women with
      EOC having levels that exceeded the range of values in women without EOC. Since
      CA 125 and pro-alphaC levels were not significantly correlated, combination of
      these markers resulted in 87% of EOC cases having elevated preoperative serum
      levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin
      secretion, especially pro-alphaC, may be useful in addition to CA 125 as a serum
      marker for EOC in postmenopausal women.

PMID- 9190985
TI  - Ovarian carcinoma metastatic to the choroid of the eye.
AB  - A case of papillary serous ovarian adenocarcinoma with choroidal metastasis to
      the eye is reported. Central nervous system metastasis of any kind is rare from
      this tumor, and only three cases of choroidal metastases have been reported to
      date. A 67-year-old women presented 2 years after diagnosis of Stage IIIC
      papillary serous ovarian adenocarcinoma with complaints of a "teardrop"-shaped
      visual field defect in her right eye. Fundoscopic examination revealed metastasis
      to the superior-temporal right choroid. No coexisting sites of recurrence were
      discovered. This case highlights the need to thoroughly and promptly investigate
      the etiology of visual field complaints in patients with a history of ovarian
      cancer.

PMID- 9190986
TI  - Neovaginal malignant melanoma following surgery and radiation for vulvar squamous
      cell carcinoma.
AB  - The causal link between therapeutic irradiation and malignant melanoma has not
      been firmly established. The authors report a novel case of a malignant melanoma
      arising from a therapeutically irradiated neovagina reconstructed from skin flaps
      following radical vulvectomy with inguinal lymph node dissection 16 years
      earlier. The diagnosis was established by light microscopy and
      immunohistochemical staining. Reports of melanoma arising from sites of previous
      radiation therapy are reviewed. Our observations suggest that therapeutic
      radiation may be a factor in the development of malignant melanoma, particularly
      in non-sun-exposed areas, including the genital tract.

PMID- 9190987
TI  - Malignant mixed mullerian tumor of the female peritoneum: treatment and outcome
      of three cases.
AB  - Three cases of malignant mixed mullerian tumor of the peritoneum are presented.
      One patient had a complete clinical and pathologic response and remains disease
      free 42 months following diagnosis. As with peritoneal carcinoma and ovarian
      sarcoma, aggressive surgical cytoreduction and postoperative chemotherapy appear
      indicated.

PMID- 9190988
TI  - Small cell carcinoma of the vagina causing Cushing's syndrome by ectopic
      production and secretion of ACTH: a case report.
AB  - BACKGROUND: Small cell carcinomas of pulmonary or extrapulmonary origin are
      neuroendocrine tumors classically associated with ectopic hormone production,
      particularly ACTH secretion resulting in Cushing's syndrome. However, ectopic
      Cushing's syndrome has not previously been reported in the setting of small cell
      carcinoma of the vagina. METHODS: A primary vaginal tumor with hepatic metastases
      was evaluated with light microscopy. Serum cortisol and plasma ACTH levels were
      evaluated by radioimmunoassay and immunoradiometric assay, respectively, during a
      standard high-dose (8 mg) overnight dexamethasone suppression test. RESULTS:
      Vaginal small cell carcinoma with hepatic metastases was demonstrated.
      Electrolyte abnormalities, elevated cortisol and ACTH levels, and failure to
      suppress ACTH secretion during high-dose dexamethasone administration confirmed
      the diagnosis of ectopic ACTH syndrome. CONCLUSIONS: This case report establishes
      a clinical association between vaginal small cell carcinoma and ectopic Cushing's
      syndrome, confirming the neuroendocrine potential of this malignancy and features
      common to small cell neoplasms originating in other sites.

PMID- 9190989
TI  - Endometrial adenocarcinoma metastatic to the scalp: case report and literature
      review.
AB  - A rare case of scalp metastasis from endometrial adenocarcinoma, demonstrating
      the poor prognosis for these patients, is reported. A 56-year-old woman with FIGO
      Stage IC, Grade 1 endometrial adenocarcinoma presented 15 months after initial
      surgery and radiation therapy with a scalp metastasis. Metastatic evaluation
      revealed widespread extrapelvic disease. She did not respond to chemotherapy and
      died 3 months after recurrence. Her course typifies that of patients with other
      cutaneous metastases as described in the literature: disease noted elsewhere at
      the time of recurrence, poor response to therapy, and death within 6 months.

PMID- 9190990
TI  - Large B-cell lymphoma of the uterine corpus: case report with immunohistochemical
      and molecular study.
AB  - Primary lymphoma of the uterine corpus (PLUC) is an extremely rare neoplasm. We
      report a case of PLUC in a 78-year-old woman with vaginal bleeding without
      hepatosplenomegaly, adenopathies, or bone marrow infiltration, classified as
      stage I. A diagnosis of diffuse large B-cell lymphoma was made in endometrial
      curettage tissue. Immunohistochemical study showed tumoral cells of B-cell
      nature. Two different polymerase chain reaction (PCR) techniques showed
      immunoglobulin heavy chain gene rearrangement and we could not demonstrate, with
      PCR technique, either Epstein-Barr virus or papilloma virus infection. Total
      hysterectomy with bilateral salpingo-oophorectomy was carried out and adjuvant
      chemotherapy was given. She was alive and free of disease after a follow-up
      period of 7 years, and the patient has been in perfect health.

PMID- 9190991
TI  - Malignant acanthosis nigricans and tripe palms in a patient with endometrial
      adenocarcinoma--a case report and review of literature.
AB  - BACKGROUND: In the world literature, uterine carcinoma associated with
      paraneoplastic malignant acanthosis nigricans and tripe palms has been mentioned
      in two review articles. Endometrial adenocarcinoma associated with malignant
      acanthosis nigricans without tripe palms has been cited in three case reports,
      and endometrial adenocarcinoma associated with tripe palms without malignant
      acanthosis nigricans has been cited in one case report. We present the case of a
      patient with endometrial adenocarcinoma associated with acanthosis nigricans and
      tripe palms which we have been following for the past 7 years. METHODS: Our 54
      year-old patient had been operated for moderately differentiated endometrial
      adenocarcinoma. She had also received postoperative radiotherapy. RESULTS: Three
      years after surgery, tripe palms and acanthosis nigricans with generalized
      pruritus occurred. After treatment with etretinate, the skin symptoms were
      somewhat mitigated while the pruritus persisted. Six years after gynecologic
      treatment, a solitary inguinal metastatic lymph node of endometrial carcinoma was
      detected. Following lymphadenectomy there was additional but not complete
      mitigation of skin symptoms including pruritus. CONCLUSIONS: In clinical practice
      the association of malignant acanthosis nigricans and tripe palms with
      endometrial adenocarcinoma is found extremely rarely. Although the survival time
      of adenocarcinoma patients with malignant acanthosis nigricans is short, our
      patient has been treated and followed for more than 7 years.

PMID- 9190992
TI  - Ovarian carcinoma initially presenting as metastatic axillary lymphadenopathy.
AB  - BACKGROUND: Ovarian carcinoma usually presents at advanced stage due to diffuse
      intraabdominal disease. Presenting signs and symptoms often relate to the degree
      of intraabdominal spread. It is rare to have distant lymph node metastases, in
      conjunction with minimal intraabdominal disease, at initial presentation. CASE: A
      78-year-old woman was noted to have an enlarged axillary lymph node on a routine,
      screening mammogram. Biopsy revealed metastatic adenocarcinoma, consistent with
      primary breast cancer. Physical examination, diagnostic mammogram, and magnetic
      resonance imaging of the breasts were normal. A pelvic computed tomography scan
      revealed a 7-cm complex, right adnexal mass. At exploratory laparotomy, there was
      minimal intraabdominal tumor burden; only a 6-cm right ovarian tumor and a single
      1.0-cm nodule adherent to the bladder peritoneum were found. After optimal
      cytoreductive surgery, she received tamoxifen for presumed metastatic breast
      cancer. One year later, recurrent disease developed in the pelvis. After
      reexploration and excision of all gross pelvic disease, a revised diagnosis of
      recurrent ovarian cancer was made, and therapy was changed to carboplatin and
      paclitaxel chemotherapy. The patient is currently without evidence of disease.
      CONCLUSION: Ovarian carcinoma usually presents with signs and symptoms related to
      the tumor burden within the peritoneal cavity. The finding of isolated, distant
      metastatic lymphadenopathy with minimal intraabdominal disease is very unusual.
      Immunohistochemical tumor markers can help determine the origin of a metastatic
      adenocarcinoma when the clinical presentation is atypical.

PMID- 9190993
TI  - Endometrial carcinoma in 45,X Turner's syndrome without hormone replacement
      therapy.
AB  - An endometrial carcinoma developing in a patient with pure Turner's syndrome was
      described. The patient showed typical Turner's phenotype and analysis of
      karyotype revealed only 45,X. Secondary sexual development had been seen until
      age 20 and she had no history of hormone replacement therapy (HRT). The enlarged
      uterus and normal appearance of bilateral ovaries were detected at laparotomy. A
      well-differentiated adenocarcinoma of the endometrium and a graafian follicle of
      the left ovary were histologically confirmed. This seems to be the first report
      of the occurrence of endometrial carcinoma in possibly pure Turner's syndrome
      without HRT.

PMID- 9190994
TI  - Vaginal radical hysterectomy.

PMID- 9190995
TI  - Increasing role of immunopathology in diagnosis of malignant mesothelioma.

PMID- 9190997
TI  - Observer variability in the histopathological reporting of needle biopsy
      specimens of the prostate.
AB  - The Scottish Pathology Consistency Group has in previous studies examined the
      consistency of histopathological reporting of biopsies from the cervix, bladder,
      bronchus, and rectum. In the current study, consisting of 100 needle biopsy
      specimens of the prostate, a single hematoxylin-eosin (H&E) slide from each case
      was circulated in batches of 10 to the 12 pathologists, who filled in a simple
      proforma. This had two sections: a diagnostic category (benign; suspicious or
      malignant) along with a standard Gleason score for those regarded as malignant.
      The majority diagnosis of the 100 cases was benign, 53; suspicious, 1; and
      malignant, 46. The Kappa value for benign cases versus others was 0.86 and for
      malignant cases versus others was 0.91. Analysis of the data on Gleason scores
      showed a value of 0.54 when cases were divided into two categories (2 to 6 v 7 to
      10) and 0.41 when three categories were used (2 to 4; 5 to 6; 7 to 10). Although
      not initially part of the design of the study, the majority diagnosis was
      compared with the original reported diagnosis. In a small subset, examination of
      further levels, basal cell antibody staining, along with further clinical
      information, was obtained. With this added information, it appears that there
      were probably 52 benign and 48 malignant cases. Of the 48 malignant cases, the
      group majority diagnosis was malignant, 46; suspicious, 1; and benign, 1. The
      original reported diagnosis was 56 benign, 1 suspicious, and 43 malignant. The
      group therefore appeared to perform better than the original reporting
      pathologists. When compared with the results of our previous studies, this study
      has shown that the diagnosis of carcinoma of the prostate on a needle biopsy is
      robust.

PMID- 9190996
TI  - Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in
      lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues.
AB  - The differential diagnosis of pleural mesotheliomas and lung adenocarcinomas
      presents a continued challenge in the practice of surgical pathology. Paraffin
      immunohistochemistry (IHC) using different panels of antibodies can be helpful in
      some cases, but, as yet, no antigen is expressed specifically in mesotheliomas
      nor in adenocarcinomas. Using well characterized monoclonal antibodies (MAb) that
      recognized distinct mesenchymal and epithelial adhesion proteins, N-cadherin
      (13A9 MAb) and E-cadherin (E9 MAb), respectively, we found previously that in
      frozen-section IHC mesotheliomas and adenocarcinomas had distinct cadherin
      phenotypes: mesotheliomas were positive for N-cadherin, and lung adenocarcinomas
      were positive for E-cadherin. Using antigen-retrieval methods, we successfully
      extended our study to formalin-fixed, paraffin-embedded tissue sections. Tumors
      from 28 patients (14 originally diagnosed as mesotheliomas, and 14 diagnosed as
      adenocarcinomas) were stained with 13A9 MAb and E9 MAb. Review of hematoxylin
      eosin sections excluded from analysis one case previously diagnosed as
      mesothelioma, which represented a hemangiopericytoma. Of the remaining 27 cases,
      12 of 13 mesotheliomas were positive for N-cadherin and negative for E-cadherin.
      The exception was a multifocal microscopic papillary tumor of apparent
      mesothelial origin, which was negative for both N-cadherin and E-cadherin.
      Conversely, 13 of 14 adenocarcinomas were E-cadherin positive and N-cadherin
      negative except for one adenocarcinoma with focal N-cadherin expression. One case
      of a poorly differentiated adenocarcinoma invading skeletal muscle was negative
      for both 13A9 and E9. These studies confirmed the utility of the cadherin
      antibodies in distinguishing pleural mesotheliomas from lung adenocarcinomas. The
      reactivity of the cadherin-specific antibodies with antigens in paraffin sections
      make them powerful and reliable markers in the practice of diagnostic surgical
      pathology.

PMID- 9190998
TI  - The histological spectrum of chronic necrotizing forms of pulmonary
      aspergillosis.
AB  - Chronic necrotizing pulmonary aspergillosis (CNPA) is a rare locally destructive
      form of chronic aspergillosis that is recognized as a clinical syndrome, but has
      been poorly defined histologically. In this study, 10 cases of CNPA were
      evaluated from a morphological perspective. Three distinct forms of CNPA emerged.
      One form (n = 4) resembled a necrotizing granulomatous pneumonia centered around
      a central zone of infarct-like necrosis of parenchyma resulting from
      angioinvasive aspergillus. The second pattern (n = 4) was that of a granulomatous
      bronchiectatic cavity with a central fungus ball and subtle tongues of necrosis
      and inflammation extending into and through the fibrous wall of the cavity. A
      final form (n = 2) had a bronchocentric granulomatosis-like appearance with a
      necrotizing granulomatous bronchitis/bronchiolitis associated with luminal
      necrotic debris and replacement of mucosa by a palisaded histiocytic reaction.
      Despite the varied histomorphology, all patients survived the aspergillus
      infection after antifungal therapy and surgical resection. The different forms of
      pulmonary aspergillosis are briefly discussed, and the differential diagnosis,
      with particular regard to mycetomas and allergic forms of bronchocentric
      granulomatosis, is highlighted.

PMID- 9190999
TI  - Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong
      Kong Chinese and its relationship with p53 gene mutation.
AB  - There is no scientific study that has investigated the association between human
      papilloma virus (HPV) and p53 mutation in Hong Kong Chinese patients with
      esophageal cancers. The aim of this survey is to evaluate in details the
      prevalence and relationship of HPV and p53 mutation in these patients with
      esophageal squamous cell carcinomas. Fresh tissues from the resected specimens of
      70 Chinese patients (59 men, 11 women) with primary esophageal squamous cell
      carcinomas (20 well-differentiated, 36 moderately differentiated, and 14 poorly
      differentiated squamous cell carcinomas) were tested for the presence of HPV and
      p53 mutation using the polymerase chain reaction (PCR), single-strand
      conformational polymorphism (SSCP) analysis, and DNA sequencing. No HPV type 18
      was detected, whereas HPV type 16 was identified in 8.6% (6 of 75) of the cases.
      p53 mutation was found in 44% (31 of 70) of the tumors. The mean ages of HPV
      positive and HPV-negative groups of patients were 55 and 64 years, respectively
      (P = .046, t-test). There was no correlation between the prevalence of HPV and
      p53 mutation in these tumors. The presence of HPV and p53 also had no relation to
      the sex of the patients or to the grade of the carcinomas. It is concluded that
      the overall low prevalence of HPV in esophageal carcinomas may suggest that the
      virus may not play an important role in the pathogenesis of these tumors in Hong
      Kong Chinese patients. Also, p53 mutation and integrated HPV DNA are not mutually
      exclusive in esophageal cancer.

PMID- 9191000
TI  - Spindle cell carcinoma of the larynx: review of 26 cases including DNA content
      and immunohistochemistry.
AB  - Spindle cell carcinoma (SpCC) is uncommon, with a predilection for the upper
      aerodigestive tract. Its histogenesis has not been resolved, although most
      authors support the sarcomatoid carcinoma concept. Ploidy analysis and
      proliferation indices have not been reported for laryngeal SpCCs. The authors
      examined the pathological and clinical features of 26 patients (25 men, 1 woman;
      mean age, 64 years) with laryngeal SpCC treated at the Mayo Clinic from 1960 to
      1990. Twenty-three tumors were examined with digital image analysis for DNA
      content of the spindle cell population (13 tumors had a sufficient squamous
      component to be analyzed separately). The glottis was involved most frequently
      (19 patients); 21 tumors were grossly polypoid. Twenty-three tumors were
      biphasic, and three were monophasic. Overall, 17 tumors (65%) showed keratin
      positivity in the spindle cell component. Polyclonal antikeratin (15 positive
      cases), 34betaE12 (15 positive), and AE1/AE3 (12 positive) were the most
      sensitive markers. Spindle cells were diploid in 5 tumors (22%) and nondiploid in
      18 (78%); conventional squamous cell carcinoma was diploid in 4 cases and
      nondiploid in 9. DNA ploidy results were concordant between the two populations
      in 11 of 13 tumors (85%). Mean percent MIB-1 staining was 31% in the sarcomatoid
      component and 45% in the squamous component. In our primary treatment group of 22
      patients (median follow-up, 6.4 years), 4 (18%) had local recurrence, 3 (14%) had
      distant metastasis, and 4 (18%) died of disease. Presence of a nondiploid spindle
      cell population in 78% of cases of laryngeal SpCC is interpreted as evidence of a
      neoplastic rather than reactive process. Keratin positivity in nearly two thirds
      of tumors supports the theory of epithelial origin of these tumors (sarcomatoid
      carcinoma).

PMID- 9191002
TI  - Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms
      predicts shorter survival.
AB  - Certain cancers exhibit derangement of de novo fatty acid biosynthesis,
      manifested as overexpression and hyperactivity of the lipogenic enzyme fatty acid
      synthase (FAS). Correlation of elevated FAS with high tumor grade and advanced
      stage in primary breast, prostate, and colorectal cancers has drawn attention to
      the enzyme as a possible marker of poor prognosis. To find a similar utility of
      FAS in ovarian neoplasms, we compared FAS expression in 68 ovarian tumors with
      their histological features and clinical outcome. Immunohistochemical
      localization of FAS was observed in 48 (71%) cases in which staining was either
      focal (defined as positive staining in 1% to 20% of cells) or multifocal/diffuse
      (positive staining in >20% of cells). Most (83%) of the 48 cases were represented
      by endometrioid, serous, or mucinous carcinomas and malignant mixed mullerian
      tumors (MMMTs). In contrast, ovarian adenomas and tumors of low malignant
      potential (LMPs) contained little or no FAS. Association between FAS expression
      and histological diagnosis was statistically significant. The extent of FAS
      immunostaining was also predictive of prognosis. Among all patients with ovarian
      malignancies (including LMPs), median survival was 64.8 months, when their tumors
      exhibited no or focal immunostaining for FAS, as opposed to 31.2 months, when
      staining was multifocal/diffuse (P = .005). Similar median survival values were
      obtained when cases were limited to endometrioid, serous, and mucinous
      carcinomas. Short-term survival at 1 and 2 years was significantly higher in
      patients whose tumors showed no or focal expression of FAS compared with
      multifocal/diffuse expression. Thus, elevated FAS may serve as an independent
      marker for predicting poor clinical outcome in patients with ovarian cancer.

PMID- 9191001
TI  - Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and
      functional evidence for cytotoxic T lymphocyte differentiation.
AB  - Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of
      peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed
      clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas
      are limited; functional characteristics of these lymphomas are unknown. We have
      undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic,
      and functional analysis of three hepatosplenic gammadelta TCLs. All patients
      presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe
      neutropenia; terminal blastlike transformation occurred in one patient.
      Combination chemotherapy had no response in two patients, but induced complete
      remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta
      gene rearrangements were documented in each case. Two different subsets of
      gammadelta TCL were identified based on delta chain variable region usage; two
      lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and
      Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q
      and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the
      Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated
      antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector
      proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each
      lymphoma; dense core cytolytic granules were observed by electron microscopy in
      both lymphomas studied. Functional studies performed in two cases showed TCR
      mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected
      cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma
      secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These
      studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain
      functional activity in vitro, and are derived from at least two gammadelta T cell
      subsets.

PMID- 9191003
TI  - Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal
      cortical neoplasms.
AB  - Alteration of the retinoblastoma (RB) gene, located on chromosome 13q14, has been
      implicated in the pathogenesis and biological behavior of several human cancers.
      We investigated the RB gene status by Western blotting and immunohistochemical
      analysis, as well as loss of heterozygosity (LOH) at the RB locus in 21 primary
      human renal neoplasms (including 3 oncocytomas). In only 1 of 21 tumors was there
      a discrepancy between Western blot and immunochemical staining. Overall, LOH was
      noted in 6 of 12 informative cases. However, only one of the tumors with LOH at
      the RB locus had loss of RB protein expression by both Western blot and
      immunohistochemical analysis. Loss of RB function was found in 4 of 18 carcinomas
      and in none of 3 oncocytomas as determined by absent RB nuclear staining in tumor
      cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high
      stage tumors and in patients with poor outcome. These results imply that (1)
      there is likely another tumor-suppressor gene on chromosome 13 involved in renal
      carcinogenesis, (2) LOH at chromosome 13q loci may be associated with aggressive
      behavior, and (3) the loss of RB function may have a role in a subset of renal
      carcinomas.

PMID- 9191004
TI  - Expression of vascular endothelial growth factor in normal liver and
      hepatocellular carcinoma: an immunohistochemical study.
AB  - Angiogenesis is of vital importance during the development and progression of
      solid tumors. To examine the role of vascular endothelial growth factor (VEGF) in
      hepatocarcinogenesis, we evaluated the expression of peptide in normal human
      liver (n = 6) and in 36 cases of hepatocellular carcinoma (HCC). Immunoreactivity
      for VEGF was present in the extracellular matrix of the portal tracts in the
      normal and nontumor part of liver, but not in hepatocytes and bile duct
      epithelium. For HCC, variable amounts of VEGF were expressed in 13 cases (36.1%)
      of tumor cells. Using a logistic regression model, expression of VEGF was
      significantly associated with a higher proliferative index (P = .01) and
      sonographic portal vein thrombosis (P = .05). However, VEGF expression did not
      correlate with a biochemical liver profile, alpha-fetoprotein levels,
      histological grading, gender, or clinical stage of cirrhosis (P > 0.1,
      respectively). Log-rank test showed that evaluation of VEGF did not provide more
      prognostic information (P > .5) than that from tumor volume and portal vein
      thrombosis (P < .01, respectively). In addition, VEGF was always present in the
      fibrovascular stroma or pericellular matrix of HCC, although no strong
      relationship was observed with the expression of VEGF in tumor cells (P > .5).
      Our data suggested that expression of VEGF may characterize a progression toward
      higher proliferation in hepatocarcinogenesis in vivo. The relevance of VEGF
      existing in the extracellular matrix of the normal liver and HCC remains to be
      clarified.

PMID- 9191005
TI  - Pathology of lung allografts in children and young adults.
AB  - Heart-lung and lung transplantation have become acceptable therapeutic modalities
      for end-stage lung and heart conditions in children and young adults, but the
      posttransplantation pulmonary pathology in this age-group is poorly
      characterized. We present our experience with the pathology of lung
      transplantation in a cohort of 11 patients with a median age of 12.5 years, and
      median posttransplantation follow-up of 8.3 months. The findings are based on
      histological examination of 98 specimens, including five autopsy specimens from
      patients 20 years of age or younger. Our experience, combined with the data in
      other pediatric series, suggest that there is not a significant difference in the
      prevalence or severity of acute rejection or bronchiolitis obliterans (BO)
      between adult and pediatric lung transplant recipients. Lymphocytic
      bronchitis/bronchiolitis showed a more prominent association with BO in our
      series than previously reported in adult studies. Chronic vascular rejection in
      the pediatric lung transplant recipients can occur earlier than reported in
      adults and is associated with a grave prognosis. Overwhelming infection was a
      major cause of death in our experience. In particular, our data combined with the
      previous reports indicate that adenoviral pneumonia is a relatively common
      pathogen in the pediatric population and is a major cause of mortality in this
      age-group.

PMID- 9191006
TI  - Immunohistochemical examination of proliferative potentials and the expression of
      cell cycle-related proteins of intracranial chordomas.
AB  - The difference in biological features between recurrent and nonrecurrent
      intracranial chordomas has not been studied. In this study, proliferative
      potentials of chordomas were studied with an immunohistochemical staining method,
      mainly using anti-Ki-67 antibody, MIB-1, which is known to be available for
      archival paraffin sections, together with immunohistochemical studies on the
      expression of cell cycle or apoptosis-related proteins, including p53, cyclin D1,
      and bcl-2 proteins. The correlation among MIB-1 staining indices, the
      immunoreactivities of these proteins, and clinical courses of intracranial
      chordomas were analyzed retrospectively, and the statistically significant
      correlation between MIB-1 staining index (SI) and recurrence has been clarified.
      The mean MIB-1 SI of recurrent tumors was 10.2%, being shown to be higher than
      that of nonrecurrent tumors (2.8%). The immunohistochemically positive staining
      of cell cycle-related protein, especially p53 and cyclin D1 proteins, correlated
      well with recurrence and high MIB-1 SI. In conclusion, both the examination of
      proliferative potentials of chordomas using MIB-1 SI and the study of the
      immunoreactivity of p53 and cyclin D1 proteins are important for their biological
      and histopathological analyses and the prediction of future recurrence.

PMID- 9191007
TI  - Involvement of neutrophil elastase in crescentic glomerulonephritis.
AB  - To elucidate the role of neutrophils in the tissue damage of crescentic
      glomerulonephritis (GN), we examined neutrophils infiltrated in renal tissues and
      the localization of neutrophil elastase (NE), as a neutrophil-derived tissue
      destructive mediator, using an immunohistochemical technique with antibodies
      specific for neutrophils and neutrophil elastase; the enzyme histochemical
      technique (chloroesterase staining) also was used to detect neutrophils. In
      normal controls, neutrophil infiltration was scarce, and NE was localized in
      neutrophil cytoplasm. Neutrophils were abundant in crescentic GN and infiltrated
      in the glomerulus and interstitium; the infiltrating neutrophils were often
      aggregated. NE was localized in the cytoplasm of neutrophils and also appeared
      extracellularly (in granular or diffuse patterns) in glomerular necrotizing
      lesions, crescents, ruptured portions of Bowman's capsules, and in periglomerular
      and perivascular sites of the interstitium. Moreover, urinary concentration of NE
      measured by enzyme-linked immunosorbent assay (ELISA) in crescentic GN patients
      was significantly higher than in normals (93.6 +/- 13.3 v 1.4 +/- 0.5 microg/g x
      Cr, respectively; P < .001). These data suggest that NE plays a significant role
      in renal tissue damage, especially in the formation of glomerular necrotizing and
      crescentic lesions and in periglomerular interstitial lesions of crescentic GN.

PMID- 9191008
TI  - The clinical significance of focal active colitis.
AB  - Focal crypt injury by neutrophils (cryptitis/crypt abscesses), or focal active
      colitis (FAC), is a common isolated finding in endoscopic colorectal biopsies.
      Focal active colitis is often thought of as a feature of Crohn's disease, but may
      also be seen in ischemia, infections, partially treated ulcerative colitis, and
      as an isolated finding in patients undergoing endoscopy to exclude neoplasia.
      Clinical, endoscopic, and pathological data were retrospectively reviewed from 49
      patients with focal active colitis, who had no other diagnostic findings on
      colorectal biopsy and no history of chronic inflammatory bowel disease. The
      histological findings were correlated with clinical diagnoses. Follow-up
      information was available for 42 of 49 focal active colitis patients. None
      developed inflammatory bowel disease; however, 19 patients had an acute self
      limited colitis-like diarrheal illness, 11 had incidental focal active colitis
      (patients without diarrhea that were endoscoped to exclude colonic neoplasia and
      found to have asymptomatic FAC), 6 had irritable bowel syndrome, 4 had antibiotic
      associated colitis, and 2 had ischemic colitis. Twenty patients were
      immunosuppressed, and 19 were taking nonsteroidal anti-inflammatory drugs. No
      histological features predicted final diagnoses. FAC did not predict the
      development of chronic colitis, even when mild crypt distortion or slight basal
      plasmacytosis was present. The preponderance of acute self-limited colitis and
      antibiotic-associated colitis among the FAC patients, along with the high number
      of immunosuppressed patients, support the conclusion that most FAC cases are
      infectious. The incidental detection of FAC in patients undergoing endoscopy to
      exclude colonic neoplasia was not clinically significant. The role of
      nonsteroidal anti-inflammatory drugs in FAC deserves further study.

PMID- 9191009
TI  - Expression of E-cadherin and N-cadherin in surface epithelial-stromal tumors of
      the ovary distinguishes mucinous from serous and endometrioid tumors.
AB  - This study examines the expression of E-cadherin and N-cadherin in the most
      common epithelial tumors of the ovary. The homotypic interactions of distinctive
      members of the cadherin family of cell-cell adhesion molecules segregate cells
      into tissues during embryonic development, and their expression in tumors can be
      used to trace the histogenesis of tumor cells. Because the surface epithelium of
      the ovary is a modified mesothelium, we speculated that the expression of E
      (epithelial)-cadherin and N (neural, mesodermal)-cadherin may provide clues about
      the controversial origin of common epithelial ovarian tumors.
      Immunohistochemistry was performed in paraffin sections using well-characterized
      monoclonal antibodies to E- and N-cadherin and heat-induced antigen-retrieval
      methods. We found that serous and endometrioid tumors express both E- and N
      cadherin. In contrast, mucinous tumors strongly express E-cadherin, but no N
      cadherin. The presence of N-cadherin in serous and endometrioid tumors traces
      their origin to the mesoderm-derived ovarian surface epithelium. The absence of N
      cadherin in mucinous tumors clearly distinguishes them from the former,
      suggesting histogenesis from a cell lineage other than the ovarian surface
      epithelium or aberrant differentiation mechanisms associated with neoplastic
      transformation.

PMID- 9191010
TI  - MN antigen expression in normal, preneoplastic, and neoplastic esophagus: a
      clinicopathological study of a new cancer-associated biomarker.
AB  - Recently, a novel tumor-associated protein, termed MN, has been described in
      carcinomas of the uterine cervix, where its expression has been shown to be
      associated with malignant transformation. Because malignant transformation in the
      esophagus develops through a dysplasia-carcinoma sequence similar to that which
      occurs in the cervix, this study was performed to evaluate MN expression in
      normal, preneoplastic, and neoplastic tissues of the esophagus. Esophageal tumor
      resection specimens from 27 patients (12 squamous cell carcinomas, one multifocal
      squamous dysplasia, 10 Barrett's-associated adenocarcinomas, two Barrett's
      esophagus with dysplasia, two adenosquamous carcinomas) were
      immunohistochemically stained with a monoclonal antibody (clone M75) directed
      against the MN antigen. The localization of MN antigen, as well as the proportion
      of positively stained cells, were determined in sections of normal, dysplastic,
      and carcinomatous tissues. The staining characteristics were correlated with the
      pathological features of the tumors. Weak intracellular MN expression was
      detected only in the basal cells of normal squamous epithelium. However, inflamed
      and reactive squamous epithelium showed increased staining in the basal layer and
      in the overlying mature squamous cells. MN expression was significantly increased
      in dysplastic squamous epithelium (P < .001). All esophageal squamous cell
      carcinomas (100%) stained positively for MN antigen, where the pattern of
      staining was predominantly membranous. However, the degree of MN staining did not
      correlate with any of the pathological features of the tumors. In Barrett's
      epithelium, MN stained positively in all types of metaplastic cells and showed no
      difference in dysplastic epithelium. In contrast to squamous cell carcinomas,
      only 80% of esophageal adenocarcinomas were positive for MN, but the degree of MN
      expression was inversely correlated with histological tumor differentiation (P <
      .015). The results of this study suggest that (1) the tumor-associated MN antigen
      may play a role in proliferation and regeneration in esophageal squamous
      epithelium, and (2) loss of MN expression may be related to cancer progression in
      Barrett's-associated adenocarcinomas.

PMID- 9191011
TI  - Florid reactive periostitis.
AB  - An 11-year-old boy developed florid reactive periostitis several years after
      minor trauma. The symptoms responded initially to antibiotics, but after
      cessation, rapidly recurred and progressed, requiring a ray amputation to relieve
      the pain and to achieve a functional hand. The reactive periostitis affected the
      volar aspect of two adjacent phalanges with sparing of the intervening joint,
      confirming that this is a reactive process rather than a benign neoplasm.

PMID- 9191012
TI  - Microsatellite instability in KSHV/HHV-8 positive body-cavity-based lymphoma.
AB  - Body-cavity-based lymphoma (BCBL) is a rare non-Hodgkin-'s lymphoma (NHL) type
      growing in liquid phase in the body cavities. Virtually all BCBL associate with
      Kaposi's sarcoma-associated herpesvirus/human herpesvirus type-8 infection in the
      absence of molecular alterations typical of other NHL categories. Microsatellite
      instability (MSI), a specific variant of genomic instability frequently
      associated with human cancers, has not been tested in BCBL thus far. In this
      report, we have analyzed the presence of MSI in the tumor cells of a male patient
      affected by AIDS-related BCBL. The genomic configuration of 12 distinct
      microsatellite loci was investigated by polymerase chain reaction amplification
      of DNA obtained from the patient's tumor cells and from autologous peripheral
      blood mononuclear cells. MSI was observed at 4/12 microsatellite repeats tested.
      Absence of the germline allele at one microsatellite locus mapping to chromosome
      X indicates that, in this BCBL case, MSI represents a clonal genetic lesion
      affecting virtually all tumor cells. These data suggest that MSI may be
      potentially involved in the pathogenesis of AIDS-related BCBL.

PMID- 9191013
TI  - Glomus tumor with diffuse infiltration of the quadriceps muscle: a case report.
AB  - A case of a diffuse growing glomus tumor with interstitial infiltration of the
      musculus vastus medialis and intermedius (quadriceps muscle) in a 21-year-old
      woman is reported. The tumor was diagnosed by needle biopsy and then removed with
      wide margins. The typical histological appearance and the immunohistochemical
      findings in the resected specimen confirmed the diagnosis. Histogenesis and the
      biological behavior of glomus tumors are discussed.

PMID- 9191014
TI  - The Center for Environmental Pathology and Toxicology at the Armed Forces
      Institute of Pathology.

PMID- 9191016
TI  - Lymphatic targeting of anti-HIV nucleosides: distribution of 2',3'-dideoxyinosine
      after intravenous and oral administration of dipalmitoylphosphatidyl prodrug in
      mice.
AB  - In the search for prodrugs of 2',3'-dideoxyinosine (ddI) with potential for
      improving the delivery of the nucleoside analogue to the lymphatic system, we
      synthesized dipalmitoylphosphatidyl-2',3'-dideoxyinosine (DPP-ddI) and its
      pharmacokinetics were investigated in mice. The disposition of ddI in plasma and
      lymph nodes was examined following intravenous and oral administration of parent
      nucleoside (100 mg/kg) and DPP-ddI (400 mg/kg, equivalent to 100 mg/kg of ddI).
      Concentrations of ddI were determined by HPLC. Pharmacokinetic parameters were
      estimated by area/moment analysis. Intravenous administration of DPP-ddI resulted
      in a pattern of lower peak concentrations of ddI and more sustained exposure of
      parent nucleoside in plasma and lymph nodes compared to administration of the
      parent nucleoside. Both ddI and DPP-ddI yielded similar AUC values in lymph
      nodes. Oral administration of the prodrug resulted in lower concentrations and
      AUC values of ddI in plasma and lymph nodes when compared to administration of
      the parent nucleoside. The bioavailability of ddI following ddI and DPP-ddI
      administration was 15 and 8%, respectively. The results of the present study
      demonstrate that DPP-ddI administered intravenously shows potential for targeting
      and sustaining level of ddI in the nodular lymphatic tissues.

PMID- 9191015
TI  - In vitro antiviral activities of myristic acid analogs against human
      immunodeficiency and hepatitis B viruses.
AB  - A group of myristic acid analogs, designed as alternative substrates for N
      myristoyltransferase (NMT), were evaluated against human immunodeficiency virus
      (HIV), hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) in vitro.
      Antiviral potency was increased when S or O was substituted for -CH2- in myristic
      acid and selectivity was affected by the presence and position of the heteroatoms
      and phenyl groups. A correlation was established among anti-HIV activity, Log P
      and Log D7.4 and between anti-HIV activity and carbonyl-heteroatom interatomic
      distances in the myristoyl analogs. 12-Thioethyldodecanoic acid 6 was moderately
      active (EC50 = 9.37 microM) against HIV-infected T4-lymphocytes (CEM-SS cell
      line), and it exhibited in vitro activity (EC50 = 17.8 microM) against HBV
      producing 2.2.15 cell cultures derived from a human hepatoblastoma cell line (Hep
      G2). 12-Methoxydodecanoic acid 1 exhibited in vitro activity (EC50 = 20-30
      microM) against hepatitis B in the HBV DNA-transfected 2.2.15 cell line. At a
      concentration of 10 microg/ml, none of the fatty acids significantly inhibited
      the replication of DHBV in infected hepatocytes.

PMID- 9191017
TI  - Inhibition of coxsackievirus B3 carrier state infection of cultured human
      myocardial fibroblasts by ribavirin and human natural interferon-alpha.
AB  - As enterovirus infections of the heart cause myocarditis and eventually
      congestive heart failure, the antiviral activity of ribavirin was studied in
      coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial
      fibroblasts. Cultures were infected 7 days before application of ribavirin and
      effects were evaluated over a period of 16 days by plaque assays and in situ
      hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin
      was highly active in reducing infectious virus yields in human myocardial
      fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x
      10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls).
      Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny
      in two of three cultures, and reduced the number of infected cells from 14.3 to
      0.3% as determined by in situ hybridization, whereas up to 3200 microg
      ribavirin/ml did not result in a significant cytotoxic effect. Interaction with
      interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the
      number of infected cells and virus yields. In conclusion, our results suggest a
      cell-specific high activity of ribavirin in human myocardial fibroblasts and
      indicate the importance of using organ-specific cells for testing antiviral
      agents in myocarditis. Furthermore, the usefulness of in situ hybridization for
      determining the long term effects of antivirals in carrier state cell cultures
      was demonstrated.

PMID- 9191018
TI  - Inhibitory activity of 3'-fluoro-2' deoxythymidine and related nucleoside
      analogues against adenoviruses in vitro.
AB  - Antiviral effects of nucleoside analogues against human adenoviruses (ADV)
      belonging to subgroup B (ADV3) and C (ADV2) were comparatively analysed using
      focus reduction assay on Fogh and Lund (FL) cells. 3'-Fluoro-2'-deoxythymidine
      (FTdR), 3'-fluoro-2'-deoxyuridine (FUdR), 2',3'-dideoxycytidine (ddC) and 3'
      fluoro-2'-deoxyguanosine (FGdR) emerged as potent and selective inhibitors. They
      were nontoxic for the FL cells at the tested doses. FTdR was proved to be the
      most effective inhibitor against both serotypes ADV2 and ADV3 (0.05 microM/0.02
      microM). The inhibitory effect of FTdR was also analyzed on the level of viral
      proteins and viral DNA synthesis using radioimmunoprecipitation and PCR,
      respectively. Neither the main structural protein of ADV, the hexon, nor viral
      DNA could be detected in ADV-infected FL cells that had been exposed to FTdR.

PMID- 9191019
TI  - Protection of hu-PBL-SCID/beige mice from HIV-1 infection by a 6-mer modified
      oligonucleotide, R-95288.
AB  - We analyzed the anti-HIV-1 activity of an oligonucleotide derivative, R-95288, in
      severe combined immunodeficient (SCID/beige) mice transplanted with normal human
      peripheral blood leukocytes (PBLs), designated hu-PBL-SCID/beige mice. The human
      chimeric mice were inoculated with HIV-1(CC1) 3 weeks after the transplantation
      and sacrificed 2 weeks later. Virus infection was determined by coculture of
      splenocytes with fresh human PBLs and also by detection of HIV- specific DNA
      sequences using the polymerase chain reaction. No evidence of infection was
      observed in mice treated with R-95288 (100 mg/kg/day) using intraperitoneal
      delivery by osmotic minipumps starting 1 day before virus challenge. In contrast,
      virus infection was observed in over 80% of the saline-treated control mice. In
      addition, partial inhibition of HIV-1 infection was obtained in mice treated
      subcutaneously with R-95288 (100 mg/kg/day). Toxicity towards the engrafted human
      cells was not observed by flow cytometric analysis. Moreover, R-95288 failed to
      inhibit lymphocyte proliferation (CC50 > 400 microg/ml), while 90% inhibition of
      HIV-1 replication was achieved at 3.1 microg/ml in vitro. These results suggest
      the ability of R-95288 to protect the human chimeric mice against HIV-1
      infection.

PMID- 9191020
TI  - Lack of mitochondrial toxicity in CEM cells treated with carbovir.
AB  - Carbovir (CBV) is a guanine nucleoside analog with potent in vitro anti-HIV
      activity. A prodrug of CBV is currently being evaluated in clinical trials as a
      potential agent for the treatment of AIDS. The ability of CBV to inhibit
      mitochondrial DNA synthesis in intact CEM cells was evaluated in the present
      study, because most of the currently available anti-HIV nucleoside analogs have
      significant toxicities that result from their inhibition of mitochondrial DNA
      synthesis. No delayed cytotoxicity was observed in CEM cells treated with 50
      microM CBV for 4 weeks. In addition, CBV at concentrations as high as 1 mM did
      not cause a decline in mitochondrial DNA levels and only minimally increased the
      concentration of lactic acid in the medium. In contrast to these results with
      CBV, treatment of CEM cells with 0.5 microM 2',3'-dideoxycytidine resulted in
      delayed cytotoxicity, a decrease in mitochondrial DNA content and increases in
      lactic acid levels in the medium. These results indicated that treatment of CEM
      cells with CBV did not result in the inhibition of mitochondrial DNA synthesis
      and suggested that treatment of AIDS patients with CBV, or a prodrug of CBV,
      would not result in some of the toxicities seen with the other anti-HIV
      nucleoside analogs.

PMID- 9191021
TI  - Suppressive effects of destruxin B on hepatitis B virus surface antigen gene
      expression in human hepatoma cells.
AB  - Destruxin B, a cyclodepsipeptide was originally identified as a plant pathogen
      from the fungus, Alternaria brassicae. We examined the antiviral activity of
      destruxin B and found that it suppresses the expression of the hepatitis B viral
      surface antigen (HBsAg) gene in human hepatoma Hep3B cells which carry an
      integrated viral gene in its chromosome. In contrast, destruxin B shows no
      cytotoxic effect on the viability of the cells. Furthermore, it can be shown that
      destruxin B can reversibly suppress HBsAg production by Hep3B cells in a
      concentration-dependent manner with EC50 of 0.5 microM. Northern blot analysis
      indicates that the suppression of HBsAg gene expression by destruxin B is mainly
      at the mRNA level. Destruxin B not only suppresses the endogenously expressed
      HBsAg in the Hep3B cells but also suppresses the HBsAg produced either from the
      stable transfected HBV DNA in another human hepatoma HuH-7 cell line which carry
      no endogenous HBV genome. These results suggest that destruxin B may have future
      potential for development as a specific anti-HBV drug.

PMID- 9191022
TI  - DNA polymerase delta, an essential enzyme for DNA transactions.
AB  - Many DNA transactions, such as replication, repair and recombination involve DNA
      synthesis and consequently require the action of DNA synthesizing enzymes called
      DNA polymerases (Pol). Eukaryotic cells contain at least six different Pols,
      named alpha, beta, gamma, delta, epsilon, and zeta. Among them Pol delta occupies
      important roles in DNA replication, nucleotide excision repair, base excision
      repair and VDJ recombination. Pol a has been extremely conserved in evolution
      from yeast to man. The function of Pol delta must be considered in the context of
      two other factors, called proliferating cell nuclear antigen and replication
      factor C, two protein complexes that build together the moving platform for Pol
      delta. This moving platform provides an important framework for dynamic
      properties of an accurate Pol delta such as its recruitment when its function is
      needed, the facilitation of Pol delta binding to the primer terminus, the
      increase in Pol delta processivity, the prevention of non-productive binding of
      the Pol delta to single-stranded DNA, the release of Pol delta after DNA
      synthesis and the bridging of Pol delta interactions to other replication
      proteins. In this review we summarize the current knowledge of Pol delta and will
      focus in particular to its structural conservation, its functional tasks in the
      cell and its interactions with other proteins.

PMID- 9191023
TI  - Topography of ribosomes and initiation complexes from rat liver as revealed by
      atomic force microscopy.
AB  - Atomic force microscopy (AFM) was used to image ribosomes and ribosomal subunits
      (60S, 40S and native 40S ribosomal subunits) isolated from rat liver. A variety
      of topographic images were obtained directly and found to be consistent with
      models established by other biophysical methods. In addition, the ternary complex
      of eIF-2 x GTP x Met-tRNA(i) and the 43S preinitiation complex have been
      discerned by AFM directly. Detailed information about the binding sites for eIF
      1A, eIF-2, eIF-3, and Met-tRNA(i) on the 40S ribosomal subunit was derived from
      the AFM images. Finally, factors which may give rise to artifactual images,
      namely, convolution of the AFM tip on ribosomes, surface tension collapse effect
      and dehydration, are discussed. This work demonstrates that AFM is useful for
      imaging ribosomes and translational complexes and provides valuable information
      that can be used to complement other well-established techniques.

PMID- 9191024
TI  - Transcription factor C/EBPalpha: novel sites of expression and cloning of the
      human gene.
AB  - We describe the characterization of recombinant clones for the human
      transcription factor CCAAT/enhancer binding protein alpha (hC/EBP alpha). The
      intronless hC/EBP alpha gene is almost 90% homologous to its rat and mouse
      counterparts. The gene copies of more distant species are less conserved, but the
      alignment reveals a striking homology in five regions, of which four may be
      involved in transactivation functions while the fifth concerns the carboxy
      terminal bZip sequences (basic region and leucine zipper) mediating sequence
      specific DNA-binding. In addition to the usual expression sites, significant
      transcript levels were detected in the epidermal compartment of human skin and in
      rat aorta by northern analysis. The presence of hC/EBP alpha is further
      documented by immunohistochemical analysis of human skin biopsies and cultured
      keratinocytes showing the nuclear presence of the protein, notably in the
      suprabasal layers of the epidermis and in human keratinocytes induced to
      differentiate.

PMID- 9191026
TI  - Mouse DNA methyltransferase (MTase) deletion mutants that retain the catalytic
      domain display neither de novo nor maintenance methylation activity in vivo.
AB  - The mammalian genome encodes a DNA cytosine-5-methyltransferase (MTase) of about
      170 kDa that is apparently responsible for both de novo and maintenance
      methylation at CpG sites. Both methylation activities have to be regulated
      accurately to ensure correct developmental and cell type-specific gene activity.
      Distorted DNA methylation patterns have been associated with cell aging and
      diseases such as cancer and fragile X syndrome. Structural and functional in
      vitro studies of the mouse MTase have indicated that the enzyme has both a
      regulatory and a catalytic region located in the N-terminal and C-terminal parts
      of the protein, respectively. The regulatory region includes the nuclear
      localization signal (NLS), the sequence for DNA targeting and the Zn-binding
      domain. The catalytic domain carries the ten consensus sequence motifs specific
      for all known pro- and eukaryotic DNA cytosine-5-methyltransferases. In an
      attempt to separate regulatory and catalytic functions of the enzyme in vivo, we
      have tested various deletion mutations by means of transient and stable cell
      transfection experiments. Expression of the transgenes, all of which retained the
      C-terminal catalytic domain, was monitored by immunofluorescence staining,
      Northern blot analysis and SDS gel electrophoresis. Despite high levels of
      transgene expression, the truncated MTase molecules exhibited neither de novo nor
      maintenance methylation activity. These findings might indicate that in vivo, an
      efficient control mechanism prevents the ectopic activity of the DNA MTase that
      is structurally compromised in its N-terminal regulatory region.

PMID- 9191025
TI  - Functional analysis of the yeast 40 kDa cyclophilin Cyp40 and its role for
      viability and steroid receptor regulation.
AB  - We have identified and characterized a homolog of the 40 kDa cyclophilins in the
      budding yeast Saccharomyces cerevisiae. At the amino acid level, this novel yeast
      cyclophilin, termed Cyp40, is 47% identical to human cyclophilin-40. Recombinant
      Cyp40 produced in bacteria has a peptidyl-prolyl cis-trans isomerase activity
      with a catalytic efficiency (k[cat]/K[m]) of 0.5 x 10(6)M(-1)s(-1), which can be
      inhibited by cyclosporin A with an IC50 value of 60nM. Using a polyclonal
      antibody against Cyp40 we have found that Cyp40 is predominantly cytoplasmic, and
      that its expression is induced 3-4-fold by heat shock. Moreover, Cyp40 can be
      coprecipitated from yeast extracts with the cytosolic molecular chaperone Hsp90.
      Surprisingly, a Cyp40-deficient yeast strain is fully viable at normal and
      elevated temperatures. Cyp40 is also dispensable for normal regulation of
      vertebrate steroid receptors in yeast. While other immunophilins could
      conceivably compensate a Cyp40 defect, our results are compatible with the notion
      that immunophilins may be fortuitous partners in the biochemically established
      steroid receptor-Hsp90 complex.

PMID- 9191027
TI  - Dam methyltransferase from Escherichia coli: kinetic studies using modified DNA
      oligomers: nonmethylated substrates.
AB  - Steady-state kinetics of the N6-adenine Dam methyltransferase have been measured
      using as substrates non-self-complementary tetradecanucleotide duplexes that
      contain the GATC target sequence. Modifications in the GATC target sequence of
      one or both of the strands included substitution of guanine by hypoxanthine,
      thymine by uracil or 5-ethyl-uracil and adenine by diamino-purine (2-amino
      adenine). Thermodynamic parameters for the 14-mer duplexes were also determined.
      DNA methylation of duplexes containing single dl for dG substitution of the Dam
      recognition site was little perturbed compared with the canonical substrate.
      Replacement of dG residues by dl in both strands resulted in a decrease of the
      specificity constant. Substitution in both strands appears to be cumulative.
      Substitution of the methyl-accepting adenine residues by 2-amino-adenine resulted
      in surprisingly little perturbation. Dam methyltransferase is rather tolerant to
      different substitutions. The results show much less spread than those for the
      analogous hemimethylated substrates studied previously (Marzabal et al., 1995).
      The absence of the methylation marker appears to be deleterious to the
      specificity of the transition state of the active complex, while the binding of
      the DNA substrate to the enzyme appears to be mostly determined by the
      thermodynamic stability of the DNA duplex.

PMID- 9191028
TI  - Neutrophils in beige mice secrete normal amounts of cathepsin G and a 46 kDa
      latent form of elastase that can be activated extracellularly by proteolytic
      activity.
AB  - Among other phenotypic defects, the beige mouse is susceptible to infection and
      has large neutrophil granules that apparently secrete a decreased amount of
      elastolytic activity. We have shown using in vitro methods that cytosolic
      inhibitors in beige neutrophils are normal. Although cathepsin G is tightly bound
      to lysosomal membranes, normal amounts of activity are released in response to
      degranulating agents. Decreased elastolytic activity is secreted by beige
      neutrophils because elastase is present in the granules as a 46 kDa proenzyme,
      which can be activated extracellularly by a protease-dependent mechanism. The
      current experiments were undertaken to explore the in vivo functions of
      neutrophils from C57 BI/6J (bg/bg) beige mice using the model of casein-induced
      acute peritonitis; normal C57 BI/6J (+/+) mice served as controls. The kinetics
      of neutrophil accumulation in the peritoneum were normal, suggesting normal
      neutrophil migration. Cathepsin G activity in the cell-free supernatant of
      peritoneal lavage fluid was normal; elastolytic activity was initially very low
      but increased to about twice baseline level after 4 h at 25 degrees C and to
      about 20-fold at 36 h. The appearance of this activity was inhibited to varying
      degree (54 to 83%) by different protease inhibitors (pepstatin, antipain,
      aprotinin, leupeptin and chymostatin). We conclude that the decreased amount of
      elastolytic activity secreted by beige neutrophils into an inflammatory exudate
      is due to a genetic defect that results in production of a 46 kDa proelastase
      rather than the normal 29 kDa active elastase; the proelastase can be
      spontaneously activated by a protease-dependent mechanism. In light of these
      data, the use of the beige mouse as a model for the Chediak-Higashi syndrome, and
      as a model in which neutrophils do not produce elastase, must be reconsidered.

PMID- 9191029
TI  - Influences of intraperitoneally and dietary administered vitamin E and selenium
      on the lipid composition in reproductive organs of male animals.
AB  - The aim of this work was to determine the protective effect of intraperitoneally
      and dietary administered vitamin E and selenium (Se) on the total lipid,
      cholesterol, and fatty acid composition in rat and lamb testes. The level of
      total lipid in rat testes was significantly decreased (p < 0.001) in the
      combination group as compared to the control group but slightly decreased in lamb
      testes (p < 0.05). In addition, the level of total lipid in lamb testes was
      significantly decreased (p < 0.001) by the Se alone. The content of total
      cholesterol in rats was higher in the Se group and its level in lamb testes was
      higher in the vitamin E groups than in the control group (p < 0.001). In rats
      testes, the amounts of palmitic, oleic, arachidonic acids, the total fatty acid,
      total unsaturated and total omega 6 acids were higher (p < 0.001) in the Se
      group. The proportions of palmitic and arachidonic acids were reduced in the
      vitamin E group and linoleic acid, total unsaturated, and total omega 6 fatty
      acids were high (p < 0.05) in the vitamin E and combination groups. In lamb
      testis tissues, the amounts of palmitic, arachidonic, total unsaturated and total
      omega 6 fatty acids were decreased in the vitamin E group in comparison to the
      control (p < 0.05). However, the amounts of arachidonic and total omega 6 fatty
      acids increased (p < 0.05) in the Se group. The proportions of arachidonic acid,
      total unsaturated fatty acid and total omega 6 fatty acids were high (p < 0.05)
      in the Se and combination groups. We concluded that the level of total lipid in
      testis tissues was reduced by dietary and intraperitoneally administered vitamin
      E and Se together. In contrast, it seems that the proportions of unsaturated and
      essential fatty acids in examined tissues are increased by vitamin E and Se.

PMID- 9191030
TI  - Protein disulfide isomerase in spore germination and cell division.
AB  - Protein disulfide isomerase (PDI) is a protein of the endoplasmic reticulum (ER)
      that is essential for the unscrambling of nonnative disulfide bonds. Here, we
      have determined the importance of PDI to both spore germination and vegetative
      cell division. To vary the concentration of PDI in the ER, we used plasmids that
      direct the expression of rat PDI fused at its N terminus to either the alpha
      factor pre-pro segment or the alpha-factor pre sequence, and fused at its C
      terminus to either the mammalian (KDEL) or the yeast (HDEL) ER retention signal.
      Classical yeast genetic (tetrad) analyses, and plasmid loss and plasmid shuffling
      experiments were used to evaluate the ability of these constructs to complement
      haploid Saccharomyces cerevisiae cells in which the endogenous PDI1 gene had been
      deleted. We find that basal levels of PDI in the ER are sufficient for vegetative
      growth. In contrast, high levels of PDI in the ER are required for efficient
      spore germination. Thus, catalysis of the unscrambling of nonnative disulfide
      bonds in cellular proteins is more important during spore germination than during
      vegetative cell division.

PMID- 9191032
TI  - Update: outbreaks of cyclosporiasis -- United States and Canada, 1997.
AB  - Since April 1997, CDC has received reports of outbreaks of cyclosporiasis in the
      United States and Canada (1,2). As of June 11, there have been 21 clusters of
      cases of cyclosporiasis reported from eight states (California, Florida,
      Maryland, Nebraska, Nevada, New York, Rhode Island, and Texas) and one province
      in Canada (Ontario). These clusters were associated with events (e.g.,
      receptions, banquets, or time-place-related exposures [meals in the same
      restaurant on the same day]) that occurred during March 19-May 25 and comprise
      approximately 140 laboratory-confirmed and 370 clinically defined cases of
      cyclosporiasis. In addition, four laboratory-confirmed and approximately 220
      clinically defined cases have been reported among persons who, during March 29
      April 5, were on a cruise ship that departed from Florida. Approximately 70
      laboratory-confirmed sporadic cases (i.e., cases not associated with events, the
      cruise, or recent overseas travel) have been reported in the United States and
      Canada. The most recent laboratory-confirmed sporadic case occurred in a person
      who had onset of symptoms on June 3.

PMID- 9191031
TI  - Cleavage of the complement system C3 component by HIV-1 proteinase.
AB  - The C3 factor of the complement system and its C3b fragment are cleaved in vitro
      by the proteinase of the human immunodeficiency virus, type 1 (HIV PR). The
      cleavage occurs in the alpha-chain of both substrates at multiple sites yielding
      a 100 kDa fragment of the C3 alpha-chain and multiple fragments of the C3b alpha
      chain. The scissile bonds are: Ala86-Glu87, Leu310-Leu311, His641-Trp642 and
      Arg649-Ser650. The resulting fragments resemble the physiologically occurring
      inactive fragments of C3: C3c and C3d, suggesting a possible biological role of
      the HIV-proteinase in the complement inactivation process.

PMID- 9191033
TI  - Lactic acidosis traced to thiamine deficiency related to nationwide shortage of
      multivitamins for total parenteral nutrition -- United States, 1997.
AB  - Since November 1996, there has been a nationwide shortage of intravenous (IV)
      multivitamins (MVIs) used in U.S. hospitals and home-health-care agencies for
      total parenteral nutrition (TPN). Patients receiving TPN without MVI
      supplementation are at risk for thiamine deficiency and life-threatening
      complications associated with severe deficiency of thiamine, a coenzyme necessary
      for oxidation of keto acids (Figure 1). This report describes three patients
      receiving TPN who had thiamine deficiency-related lactic acidosis in 1997 and
      presents recommendations for alternatives to parenteral MVI during the shortage.

PMID- 9191034
TI  - Heat-related deaths -- Dallas, Wichita, and Cooke counties, Texas, and United
      States, 1996.
AB  - During July 2-8, 1996, high maximum daily temperatures in Dallas County, Texas,
      ranged from 101 F (38.3 C) to 106 F (41.1 C), and high maximum daily heat indexes
      (a measure of the effect of combined elements [e.g., heat and humidity] on the
      body) ranged from 105 F (40.6 C) to 112 F (44.4 C). Although guidelines for
      issuing heat advisories or warnings vary by geographic location and climate, the
      National Weather Service generally suggests issuing a heat advisory when a
      daytime heat index reaches > or =105 F (> or =40.6 C), and a night time minimum
      ambient temperature of 80 F (26.7 C) persists for at least 48 hours. In Dallas
      County, the criterion used by the medical examiner's (ME's) office to designate a
      heat wave is > or =3 consecutive days of temperatures > or =100 F (37.8 C). This
      report describes four cases of heat-related death in Dallas, Wichita, and Cooke
      counties, Texas, in 1996; summarizes risk factors for this problem; and reviews
      measures to prevent heat-related morbidity and mortality. The findings in this
      report indicate that, although a large proportion of heat-related deaths occur
      during the summer and during heat waves, such deaths occur year-round.

PMID- 9191035
TI  - Lyme disease -- United States, 1996.
AB  - Lyme disease (LD) is caused by the tickborne spirochete Borrelia burgdorferi
      sensu lato and is the most common vectorborne disease in the United States.
      Surveillance for LD was initiated by CDC in 1982, and the Council of State and
      Territorial Epidemiologists designated it a nationally notifiable disease in
      January 1991. For surveillance purposes, LD is defined as the presence of an
      erythema migrans rash > or =5 cm in diameter or laboratory confirmation of
      infection with evidence of at least one manifestation of musculoskeletal,
      neurologic, or cardiovascular disease (1). This report summarizes the provisional
      number of cases of LD reported to CDC during 1996 and indicates that the number
      of cases reported to CDC was a record high.

PMID- 9191036
TI  - Malaria in an immigrant and travelers -- Georgia, Vermont, and Tennessee, 1996.
AB  - Each year, approximately 1000 cases of malaria are reported in the United States,
      nearly all among persons with histories of antecedent international travel.
      Failure to use appropriate measures to prevent infection when traveling in areas
      with endemic disease and delays in diagnosis and treatment can result in severe
      complications and death. This report presents three recent cases of malaria that
      illustrate the importance of following the fundamental measures for preventing
      malaria.

PMID- 9191037
TI  - Sarcoidosis among U.S. Navy enlisted men, 1965-1993.
AB  - Sarcoidosis is a multisystem granulomatous disease of unknown etiology with
      highest incidence among young and middle-aged adults. In the United States, the
      risk for sarcoidosis is substantially higher among blacks than among other races
      (1,2); however, the reasons for this association are unknown. In response to the
      occurrence of a case of sarcoidosis in a U.S. Navy (USN) enlisted man, CDC's
      National Institute for Occupational Safety and Health (NIOSH) analyzed USN data
      on cases of sarcoidosis diagnosed among active-duty enlisted personnel during
      1965-1993. This report summarizes the findings of this analysis, which indicate
      that the incidence of sarcoidosis declined among USN enlisted men during 1965
      1993, particularly among blacks, and that the risk for sarcoidosis was
      statistically associated with the assignment of USN enlisted men to aircraft
      carriers.

PMID- 9191038
TI  - Histidine kinases in signal transduction pathways of eukaryotes.
AB  - Autophosphorylating histidine kinases are an ancient conserved family of enzymes
      that are found in eubacteria, archaebacteria and eukaryotes. They are activated
      by a wide range of extracellular signals and transfer phosphate moieties to
      aspartates found in response regulators. Recent studies have shown that such two
      component signal transduction pathways mediate osmoregulation in Saccharomyces
      cerevisiae, Dictyostelium discoideum and Neurospora crassa. Moreover, they play
      pivotal roles in responses of Arabidopsis thaliana to ethylene and cytokinin. A
      transmembrane histidine kinase encoded by dhkA accumulates when Dictyostelium
      cells aggregate during development. Activation of DhkA results in the inhibition
      of its response regulator, RegA, which is a cAMP phosphodiesterase that regulates
      the cAMP dependent protein kinase PKA. When PKA is activated late in the
      differentiation of prespore cells, they encapsulate into spores. There is
      evidence that this two-component system participates in a feedback loop linked to
      PKA in prestalk cells such that the signal to initiate encapsulation is rapidly
      amplified. Such signal transduction pathways can be expected to be found in a
      variety of eukaryotic differentiations since they are rapidly reversible and can
      integrate disparate signals.

PMID- 9191039
TI  - Changes in histone synthesis and modification at the beginning of mouse
      development correlate with the establishment of chromatin mediated repression of
      transcription.
AB  - The transition from a late 1-cell mouse embryo to a 4-cell embryo, the period
      when zygotic gene expression begins, is accompanied by an increasing ability to
      repress the activities of promoters and replication origins. Since this
      repression can be relieved by either butyrate or enhancers, it appears to be
      mediated through chromatin structure. Here we identify changes in the synthesis
      and modification of chromatin bound histones that are consistent with this
      hypothesis. Oocytes, which can repress promoter activity, synthesized a full
      complement of histones, and histone synthesis up to the early 2-cell stage
      originated from mRNA inherited from the oocyte. However, while histones H3 and H4
      continued to be synthesized in early 1-cell embryos, synthesis of histones H2A,
      H2B and H1 (proteins required for chromatin condensation) was delayed until the
      late 1-cell stage, reaching their maximum rate in early 2-cell embryos. Moreover,
      histone H4 in both 1-cell and 2-cell embryos was predominantly diacetylated (a
      modification that facilitates transcription). Deacetylation towards the
      unacetylated and monoacetylated H4 population in fibroblasts began at the late 2
      cell to 4-cell stage. Arresting development at the beginning of S-phase in 1-cell
      embryos prevented both the appearance of chromatin-mediated repression of
      transcription in paternal pronuclei and synthesis of new histones. These changes
      correlated with the establishment of chromatin-mediated repression during
      formation of a 2-cell embryo, and the increase in repression from the 2-cell to 4
      cell stage as linker histone H1 accumulates and core histones are deacetylated.

PMID- 9191040
TI  - Translocation of a UV-damaged DNA binding protein into a tight association with
      chromatin after treatment of mammalian cells with UV light.
AB  - A UV-damaged DNA binding protein (UV-DDB) is the major source of UV-damaged DNA
      binding activity in mammalian cell extracts. This activity is defective in at
      least some xeroderma pigmentosum group E (XP-E) patients; microinjection of the
      UV-DDB protein into their fibroblasts corrects nucleotide excision repair (NER).
      In an in vitro reconstituted NER system, small amounts of UV-DDB stimulate repair
      synthesis a few fold. After exposure to UV, mammalian cells show an early dose
      dependent inhibition of the extractable UV-DDB activity; this inhibition may
      reflect a tight association of the binding protein with UV-damaged genomic DNA.
      To investigate the dynamics and location of UV-DDB with respect to damaged
      chromatin in vivo, we utilized nuclear fractionation and specific antibodies and
      detected translocation of the p127 component of UV-DDB from a loose to a tight
      association with chromatinized DNA immediately after UV treatment. A similar
      redistribution was found for other NER proteins, i.e. XPA, RP-A and PCNA,
      suggesting their tighter association with genomic DNA after UV. These studies
      revealed a specific protein-protein interaction between UV-DDB/p127 and RP-A that
      appears to enhance binding of both proteins to UV-damaged DNA in vitro, providing
      evidence for the involvement of UV-DDB in the damage-recognition step of NER.
      Moreover, the kinetics of the reappearance of extractable UV-DDB activity after
      UV treatment of human cells with differing repair capacities positively correlate
      with the cell's capacity to repair 6-4 pyrimidine dimers (6-4 PD) in the whole
      genome, a result consistent with an in vivo role for UV-DDB in recognizing this
      type of UV lesion.

PMID- 9191041
TI  - Plasma membrane targetting, vesicular budding and release of galectin 3 from the
      cytoplasm of mammalian cells during secretion.
AB  - Galectin 3, a 30 kDa galactoside-binding protein distributed widely in epithelial
      and immune cells, contains no signal sequence and is externalized by a mechanism
      independent of the endoplasmic reticulum (ER)-Golgi complex. We show here that
      hamster galectin 3 overexpressed in transfected cos-7 cells is secreted at a very
      low rate. A chimaera of galectin 3 fused to the N-terminal acylation sequence of
      protein tyrosine kinase p56(lck), Nt-p56(lck)-galectin 3, which is myristoylated
      and palmitoylated and rapidly transported to plasma membrane domains, is
      efficiently released from transfected cells indicating that movement of
      cytoplasmic galectin 3 to plasma membrane domains is a rate limiting step in
      lectin secretion. N-terminal acylation is not sufficient for protein secretion
      since p56(lck) and the chimaera Nt-p56(lck)-CAT are not secreted from transfected
      cells. The amino-terminal half of galectin 3 is sufficient to direct export of a
      chimaeric CAT protein indicating that part of the signal for plasma membrane
      translocation lies in the N-terminal domains of the lectin. Immunofluorescence
      studies show that Nt-p56(lck)-galectin 3 aggregates underneath the plasma
      membrane and is released by membrane blebbing. Vesicles of low buoyant density
      isolated from conditioned medium are enriched in galectin 3. The lectin is
      initially protected from exogenous collagenase but is later released in soluble
      protease-sensitive form from the lectin-loaded vesicles. Using murine
      macrophages, which secrete their endogenous galectin 3 at a moderate rate
      especially in the presence of Ca2+-ionophores, we were also able to trap a
      galectin 3-loaded vesicular fraction which was released into the culture
      supernatant.

PMID- 9191042
TI  - Cytomechanics of neurite outgrowth from chick brain neurons.
AB  - Mechanical tension is a direct and immediate stimulus for neurite initiation and
      elongation from peripheral neurons. We report here that the relationship between
      tension and neurite outgrowth is equally initimate for embryonic chick forebrain
      neurons. Culture of forebrain neurons was unusually simple and reliable, and some
      of these cells undergo early events of axonal-dendritic polarity. Neurite
      outgrowth can be initiated de novo by experimental application of tension to the
      cell margin of forebrain neurons placed into culture 8-12 hours earlier, prior to
      spontaneous neurite outgrowth. Experimentally induced neurite elongation from
      these neurons shows the same robust linear relationship between elongation rate
      and magnitude of applied tension as peripheral neurons, i.e. both show a fluid
      like growth response to tension. Although forebrain and sensory neurons manifest
      a similar distribution of growth sensitivity to tension (growth rate/unit
      tension), chick forebrain neurons initiated and elongated neurites at
      substantially lower net tensions than peripheral neurons. This is because, unlike
      peripheral neurons, there is no minimum threshold tension required for elongation
      in forebrain neurons; all positive tensions stimulate neurite outgrowth.
      Consistent with this observation, chick forebrain neurons showed weak retractile
      behavior in response to slackening compared to sensory neurons. Neurites that
      were slackened showed only transient elastic behavior and never actively produced
      tension, as do chick sensory neurons after slackening. We conclude that tension
      is an important regulator of both peripheral and central neuronal growth, but
      that elastic behavior is much weaker for forebrain neurons than peripheral
      neurons from the same developing organism. These data have significance for the
      understanding of the morphogenetic events of brain development.

PMID- 9191043
TI  - Pronounced cytoplasmic pH gradients are not required for tip growth in plant and
      fungal cells.
AB  - The existence of pronounced cytoplasmic pH gradients within the apices of tip
      growing cells, and the role of cytoplasmic pH in regulating tip growth, were
      investigated in three different cell types: vegetative hyphae of Neurospora
      crassa; pollen tubes of Agapanthus umbellatus; and rhizoids of Dryopteris affinis
      gametophytes. Examination of cytoplasmic pH in growing cells was performed by
      simultaneous, dual emission confocal ratio imaging of the pH-sensitive probe
      carboxy SNARF-1. Considerable attention was paid to the fine tuning of dye
      loading and imaging parameters to minimise cellular perturbation and assess the
      extent of dye partitioning into organelles. With optimal conditions, cytoplasmic
      pH was measured routinely with a precision of between +/-0.03 and +/-0.06 of a pH
      unit and a spatial resolution of 2.3 microm2. Based on in vitro calibration,
      estimated values of mean cytoplasmic pH for cells loaded with dye-ester were
      between 7.15 and 7.25 for the three cell types. After pressure injecting
      Neurospora hyphae with dextran-conjugated dye, however, the mean cytoplasmic pH
      was estimated to be 7.57. Dextran dyes are believed to give a better estimate of
      cytoplasmic pH because of their superior localisation and retention within the
      cytosol. No significant cytoplasmic pH gradient (delta pH of >0.1 unit) was
      observed within the apical 50 microm in growing cells of any of the three cell
      types. Acidification or alkalinisation of the cytoplasm in Neurospora hyphae,
      using a cell permeant weak acid (propionic acid at pH 7.0) or weak base
      (trimethylamine at pH 8.0), slowed down but did not abolish growth. However,
      similar manipulation of the cytoplasmic pH of Agapanthus pollen tubes and
      Dryopteris rhizoids completely inhibited growth. Modification of external pH
      affected the growth pattern of all cell types. In hyphae and pollen tubes,
      changes in external pH were found to have a small transient effect on cytoplasmic
      pH but the cells rapidly readjusted towards their original pH. Our results
      suggest that pronounced longitudinal gradients in cytoplasmic pH are not
      essential for the regulation of tip growth.

PMID- 9191044
TI  - Localization of five annexins in J774 macrophages and on isolated phagosomes.
AB  - Annexins are a family of structurally related proteins which bind phospholipids
      in a calcium-dependent manner. Although the precise functions of annexins are
      unknown, there is an accumulating set of data arguing for a role for some of them
      in vesicular transport and, specifically, in membrane-membrane or membrane
      cytoskeletal interactions during these processes. Here we describe our
      qualitative and quantitative analysis of the localization of annexins I-V in J774
      macrophages that had internalized latex beads, both with and without IgG
      opsonization. Our results show that whereas all these annexins are present on
      both the plasma membrane and on phagosomes, the localization on other organelles
      differs. Annexins I, II, III and V were detected on early endosomes, while only
      annexin V was seen on late endocytic organelles and mitochondria. Annexins I and
      II distributed along the plasma membrane non-uniformly and co-localized with F
      actin at the sites of membrane protrusions. We also investigated by western blot
      analysis the association of annexins with purified phagosomes isolated at
      different time-points after latex bead internalization. While the amounts of
      annexins I, II, III and V associated with phagosomes were similar at all times
      after their formation, the level of annexin IV was significantly higher on older
      phagosomes. Whereas annexins I, II, IV and V could be removed from phagosome
      membranes with a Ca2+ chelator they remained membrane bound under low calcium
      conditions. In contrast, annexin III was removed under these conditions and
      needed a relatively high Ca2+ concentration to remain phagosome bound. Because of
      their purity and ease of preparation we suggest that phagosomes are a powerful
      system to study the potential role of annexins in membrane traffic.

PMID- 9191045
TI  - Molecular cloning, over-expression, developmental regulation and
      immunolocalization of fragminP, a gelsolin-related actin-binding protein from
      Physarum polycephalum plasmodia.
AB  - FragminP is a Ca2+-dependent actin-binding and microfilament regulatory protein
      of the gelsolin family. We screened a Physarum polycephalum cDNA library with
      polyclonal fragminP antibodies and isolated a cDNA clone of 1,104 bp encoding 368
      amino acids of fragminP, revealing two consensus phosphatidylinositol 4,5
      bisphosphate-binding motifs in the central part of the protein. The first
      methionine is modified by an acetyl group, and three amino acids were missing
      from the protein coded for by the cDNA clone. Full-length recombinant fragminP
      was generated by PCR, purified after over-expression from Escherichia coli and
      displayed identical properties to native Physarum fragminP. Northern blot
      analysis against RNA, isolated from cultures at various stages of development,
      indicated that fragminP is absent from amoebae and that expression is initiated
      at an early stage during apogamic development, in a similar way to that observed
      for the profilin genes. In situ immunolocalization of fragminP in Physarum
      microplasmodia revealed that the protein is localized predominantly at the plasma
      membrane, suggesting a role in the regulation of the subcortical actin meshwork.
      Our data indicate that we have isolated the plasmodium-specific fragminP cDNA
      (frgP) and suggest that, in each of its two vegetative cell types, P.
      polycephalum uses a different fragmin isoform that performs different functions.

PMID- 9191046
TI  - Mesenchyme-mediated effects of retinoic acid during rat intestinal development.
AB  - In previous experiments we showed that intestinal development was dependent upon
      epithelial-mesenchymal cell interactions. The aim of this study was to
      investigate the possible role of retinoic acid (RA), a morphogenetic and
      differentiating agent, on the gut epithelial-mesenchymal unit. For this purpose
      we first analyzed the effects of a physiological dose of RA on 14-day fetal rat
      intestine using short-term organ culture experiments, or long-term grafts under
      the skin of nude mice. In these conditions, RA accelerated villus outgrowth and
      epithelial cell differentiation as assessed by the onset of lactase expression,
      and it also stimulated muscle and crypt formation. In order to analyze potential
      effects of RA mediated by mesenchymal cells, we isolated and characterized gut
      mucosa mesenchyme-derived cell cultures (mesenchyme-derived intestinal cell
      lines, MIC). These cells were shown to express mRNAs for retinoid binding
      proteins similar to those expressed in situ in the intestinal mesenchyme. MIC
      cells co-cultured with 14-day intestinal endoderms promoted endodermal cell
      adhesion and growth, and the addition of exogeneous RA enhanced epithelial cell
      polarization and differentiation assessed by cytokeratin and lactase
      immunostaining. Such a differentiating effect of RA was not observed on
      endodermal cells when cultured without a mesenchymal feeder layer or maintained
      in conditioned medium from RA-treated MIC cells. In the co-cultures,
      immunostaining of laminin and collagen IV with polyclonal antibodies, as well as
      alpha1 and beta1 laminin chains mRNAs (analyzed by RT-PCR) increased concurrently
      with the RA-enhanced differentiation of epithelial cells. It is worth noting that
      this stimulation by RA was also obvious on the mesenchymal cells cultured alone.
      These results show that RA plays a role in intestinal morphogenesis and
      differentiation. In addition, they indicate that RA acts on the mesenchymal cell
      phenotype and suggest that RA may modify the mesenchymal-epithelial cell
      interactions during intestinal development.

PMID- 9191047
TI  - Golgi membrane skeleton: identification, localization and oligomerization of a
      195 kDa ankyrin isoform associated with the Golgi complex.
AB  - To extend our finding of a Golgi-localized form of the membrane skeleton protein
      spectrin, we have identified an isoform of ankyrin that associates at steady
      state with the Golgi complex. Immuno-light and -electron microscopy show that
      this ankyrin isoform localizes to the perinuclear cytoplasm on tubular vesicular
      structures that co-stain with Golgi marker proteins. An antiserum raised against
      erythrocyte ankyrin, which was used to identify the Golgi ankyrin, recognized
      three prominent polypeptides of 220, 213 and 195 kDa in MDCK cells. Affinity
      purification of this antiserum against each of these MDCK cell ankyrins revealed
      that only an antibody specific for the 195 kDa form retained the ability to stain
      the Golgi complex; affinity purified antibody preparations specific for both the
      220 and 213 kDa forms stained punctate and reticular cytoplasmic structures
      distinct from the Golgi complex. Antibody specific for the 195 kDa ankyrin did
      not recognize a recently identified 119 kDa ankyrin that is also localized to the
      Golgi. The 195 kDa Golgi ankyrin binds purified erythrocyte spectrin, and rapidly
      co-sediments with Golgi beta-spectrin during brief, low speed centrifugation of
      Triton X-100 extracts of MDCK cells. Golgi ankyrin and beta-spectrin are retained
      on tubular vesicular 'Golgi ghosts' following extraction of cultured cells with
      Triton X-100. Significantly, Golgi ghost tubules containing ankyrin/spectrin are
      co-linear with individual microtubules, suggesting a role for both Golgi membrane
      skeleton and microtubules in spatial localization of the Golgi. Golgi ankyrin
      dissociates from Golgi membranes during mitosis and in cells treated with
      brefeldin A, indicating that Golgi ankyrin has a dynamic assembly state similar
      to that of Golgi spectrin and other Golgi membrane coat proteins.

PMID- 9191048
TI  - Cyclin dependent kinase 5, cdk5, is a positive regulator of myogenesis in mouse
      C2 cells.
AB  - We have examined the expression, activity and localization of cyclin dependent
      kinase 5 (cdk5), during myogenesis. Cdk5 protein was found expressed in adult
      mouse muscle. In murine C2 cells, both the protein level and kinase activity of
      cdk5 showed a marked increase during early myogenesis with a peak between 36 and
      48 hours of differentiation, decreasing as myotubes fuse after 60 to 72 hours.
      This increase in cdk5 protein level was specific for differentiation and not
      simply related to cell cycle arrest since it was not observed in fibroblasts
      grown for 48 hours in low serum medium. Indirect immunofluorescence using
      monospecific purified anti-cdk5 antibodies showed a low level cytoplasmic
      staining in proliferative myoblasts, a rapid increase in nuclear staining during
      the initial 12 hours of differentiation and a predominant nuclear staining in
      myotubes. Microinjection of plasmids encoding wild-type cdk5 into C2 myoblasts
      enhanced differentiation as assessed by both myogenin and troponin T expression
      after 48 hours of differentiation. In contrast, microinjection of plasmids
      encoding a dominant negative mutant of cdk5 inhibited the onset of
      differentiation. These data imply a previously unsuspected role for cdk5 protein
      kinase as a positive modulator of early myogenesis.

PMID- 9191049
TI  - Bcl-2 reduces lymphomagenesis in deltaV-TCRbeta transgenic mice.
AB  - Overexpression of the bcl-2 oncogene in the lymphoid compartment of transgenic
      mice prolongs the lifespan of lymphocytes and leads to a low incidence of
      lymphomas at later age. Transgenic mice carrying a mutated T-cell receptor
      lacking the variable domain (deltaV-TCRbeta) suffer from lymphocyte depletion and
      are highly predisposed to lymphoma development. We intercrossed Bcl-2-Ig and
      deltaV-TCRbeta transgenic mice to assess whether Bcl-2 could synergize with
      deltaV-TCRbeta in tumorigenesis as reported previously for other oncogenes.
      Surprisingly, bitransgenic deltaV-TCRbeta; bcl-2-Ig mice showed a reduction in
      the incidence of lymphomas. Analyses of prelymphomatous mice showed that Bcl-2
      restored some of the phenotypic aberrations caused by the deltaV-TCRbeta
      transgene in the lymphoid compartment. The inhibitory activity of Bcl-2 on
      deltaVTCRbeta-induced lymphomagenesis was not observed when both transgenes were
      crossed into the RAG-1-/- background suggesting an important role for more mature
      lymphocytes in this phenomenon. These results show that, depending on the
      specific conditions, overexpression of Bcl-2 can both promote as well as impair
      lymphoma development.

PMID- 9191050
TI  - The p53 activation and apoptosis induced by DNA damage are reversibly inhibited
      by salicylate.
AB  - Treatment of mouse (12)1/CA cells with adriamycin or irradiation with U.V.C.
      induces p53-dependent transcription of a beta-galactosidase reporter and the
      endogenous p21/Waf1/Cip1 gene. Despite the induction of Waf1, the cells arrest
      only transiently in G1 or G2, then resume growth and eventually undergo
      apoptosis. In situ analysis of beta-galactosidase activity in U.V.C.-irradiated
      cells revealed a much higher level of p53-dependent transcription in cells
      undergoing apoptosis compared to transiently arrested cells. Incubation of the
      treated cells with salicylate, which inhibits the activation of protein kinases
      and transcription factors involved in stress responses, inhibits both p53
      dependent transcription and apoptosis. The inhibition of transcription is due
      mainly to impairment of the ability of p53 to bind to DNA. The treated cells
      resume their p53-dependent programs whenever the salicylate is removed, even
      after as long as 60 h after the DNA has been damaged. Therefore, the p53
      activating signals generated by adriamycin or U.V.C. are very long lived. The
      resumption of p53-dependent transcription is not accompanied by additional
      accumulation of the p53 protein, indicating that the activation of p53 is
      regulated by a separate pathway.

PMID- 9191051
TI  - Regulation of DNA binding and transactivation in p53 by nuclear localization and
      phosphorylation.
AB  - Compelling evidence indicates that p53 acts as a transcription factor and that
      this activity is regulated by several factors including subcellular localization
      and phosphorylation status of the protein. To learn more about how these two
      processes determine whether p53 becomes activated, we studied the temperature
      sensitive murine p53, p53val135. At nonpermissive temperatures, p53val135 remains
      sequestered in the cytoplasm of cells which express it. Electrophoretic mobility
      shift assays demonstrated that, under these conditions, the protein lacked DNA
      binding activity. However, by shifting to the permissive temperature, p53val135
      became concentrated in the nucleus, hyperphosphorylated, and had acquired the
      ability to bind DNA in a sequence specific manner. This was accompanied by the
      induction of two p53 regulated genes, mdm2 and p21waf1, which indicated that
      p53val135 had become an active transcription factor. Two dimensional gel
      electrophoresis and tryptic peptide mapping showed that entry into the nucleus
      resulted in the appearance of new phosphorylated isoforms and that the protein
      had become extensively phosphorylation at the N-terminus. Notably,
      phosphorylation at the N-terminus occurred only in the nucleus, whereas
      phosphorylation at the C-terminus could occur in both the cytoplasm and the
      nucleus. Based on these observations, we suggest that phosphorylation of p53's N
      terminus is compartmentally restricted.

PMID- 9191052
TI  - The highest affinity DNA element bound by Pbx complexes in t(1;19) leukemic cells
      fails to mediate cooperative DNA-binding or cooperative transactivation by E2a
      Pbx1 and class I Hox proteins - evidence for selective targetting of E2a-Pbx1 to
      a subset of Pbx-recognition elements.
AB  - Oncoprotein E2a-Pbx1 contains the N-terminal transactivation domains of E2a and
      the majority of the homeodomain protein, Pbx1. Using recombinant proteins, both
      Pbx1 and E2a-Pbx1 heterodimerize with Hox proteins on bipartite elements, Pbx1
      binding a 5' TGAT core and Class I Hox proteins binding adjacent 3' TAAT, TTAT,
      or TGAT cores. In contrast to these in vitro results, nuclear extracts from E2a
      Pbx1-transformed cells assemble an abundant Pbx-containing complex on TGATTGAT
      that excludes E2a-Pbx1, suggesting that an uncharacterized in vivo partner
      discriminates between E2a-Pbx1 and Pbx proteins, distinguishing it from Hox
      proteins. Here, we describe the DNA-binding properties of this complex, and
      identify TGATTGAC (PCE; Pbx Consensus Element) as its optimal recognition motif.
      In vitro, the PCE fails to bind heterodimers of Class I Hox proteins plus either
      Pbx1 or E2a-Pbx1. Likewise, in vivo, the PCE fails to mediate cooperative
      transactivation by E2a-Pbx1 plus Class I Hox proteins. Thus, the PCE binds a Pbx
      dimer partner that behaves unlike Class I Hox proteins. Competition analysis
      indicates that the Pbx-containing complex that binds the PCE also binds the
      TGATTGAT Pbx-Hox element and binds promoter elements required for tissue-specific
      expression of a number of cellular genes. Thus, different Pbx partners dictate
      targetting of Pbx heterodimers to related DNA motifs that differ in the sequence
      of their 3' half-sites, and E2a-Pbx1 heterodimerizes with only a subset of Pbx
      partners, restricting its potential DNA targets.

PMID- 9191053
TI  - Regulated ectopic expression of cyclin D1 induces transcriptional activation of
      the cdk inhibitor p21 gene without altering cell cycle progression.
AB  - Cyclin D1 plays a key regulatory role during the G1 phase of the cell cycle and
      its gene is amplified and overexpressed in many cancers. To address the
      relationship between cyclin D1 and other cell cycle regulatory proteins, we
      established human glioma and rodent fibroblast cell lines in which cyclin D1
      expression could be regulated ectopically with tetracycline. In both of these
      cell lines, we found that ectopic expression of cyclin D1 in asynchronously
      growing cells was accompanied by increased levels of the p53 tumor suppressor
      protein and the cyclin/cdk inhibitor p21. Despite the induction of these cell
      cycle inhibitory proteins, cyclin D1-associated cdk kinase remained activated and
      the cells grew essentially like that of the parent cells. Although growth
      parameters were unchanged in these cells, morphological changes were clearly
      identifiable and anchorage independent growth was observed in NIH3T3 cells. In a
      first step toward elaborating the mechanism for cyclin D1-mediated induction of
      p21 gene expression we show that co-expression of E2F-1 and DP-1 can specifically
      transactivate the p21 promoter. In support of these findings and a direct effect
      of E2F on induction of p21 gene expression a putative E2F binding site was
      identified within the p21 promoter. In summary, our results demonstrate that
      ectopic expression of cyclin D1 can induce gene expression of the cdk inhibitor
      p21 through an E2F mechanism the consequences of which are not to growth arrest
      cells but possibly to stabilize cyclin D1/cdk function.

PMID- 9191054
TI  - Differentiation dependent expression and distinct subcellular localization of the
      protooncogene product, PEBP2beta/CBFbeta, in muscle development.
AB  - The Pebpb2/Cbfb gene encodes the non-DNA binding subunit of the heterodimeric
      transcription factor, PEBP2/CBF. To examine the expression of the
      PEBP2beta/CBFbeta protein in vivo, we carried out immunohistochemistry using the
      tissues from adult mice as well as embryos. Although PEBP2beta/CBFbeta was
      detected in various tissues to various degrees, interesting features of
      expression were observed in the skeletal myogenic cells. Here PEBP2beta/CBFbeta
      was found mainly to occur as cytoplasmic staining and the intensity of this
      staining increased depending on the differentiation stage of the cells. In the
      undifferentiated myoblasts PEBP2beta/CBFbeta was undetectable, whereas moderate
      levels of PEBP2beta/ CBFbeta were detected in the elongated and aligned myocytes.
      PEBP2beta/CBFbeta appeared to accumulate further when the cells fused to each
      other to become multinucleated myotubes. Once the muscle fibers were established,
      PEBP2beta/CBFbeta was relocated onto or around the Z-lines. PEBP2beta/CBFbeta was
      also detected in the cytoplasm of cardiac myocytes and in the smooth muscle cells
      of the digestive tract. In all the above, the skeletal myotubes were the only
      case that showed both nuclear and cytoplasmic staining of PEBP2beta/CBFbeta.
      Thus, we could show differentiation dependent pattern of PEBP2beta/CBFbeta
      expression in muscle development and establish PEBP2beta/CBFbeta to be a
      cytoplasmic as well as nuclear protein in vivo.

PMID- 9191055
TI  - Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723
      phosphospecific antibody.
AB  - The macrophage colony stimulating factor receptor (CSF-1R), the product of the c
      fms proto-oncogene, plays an important role in regulating the normal
      proliferation and differentiation of macrophages and trophoblasts. However, the
      abnormal expression of CSF-1R transcripts and protein by human breast carcinomas
      has been shown to correlate with advanced stage and poor prognosis. Ligand
      activated CSF-1R dimers transphosphorylate several tyrosines in their cytoplasmic
      domains which provide recognition sites for various effector proteins in multiple
      signal transduction pathways. In cells transformed by the c-fms oncogene, one of
      the major CSF-1R phosphotyrosines, pTyr723 is important for phenotypic expression
      of anchorage-independent growth and metastasis. In order to investigate the
      relationship between receptor activation/phosphorylation and cellular phenotypes
      in vitro and in vivo, we prepared a CSF-1R phosphorylation-state specific
      antibody raised against a specific phosphopeptide of CSF-1R, which included
      phosphorylated tyrosine 723. On immunoblots of lysates from cells expressing CSF
      1R, this antibody recognizes phosphorylated CSF-IR in CSF-1 stimulated cells but
      not in unstimulated cells. As an immunohistochemical reagent, this antibody
      stained 52% of invasive human breast tumors (72% of CSF-1R positive cases) in a
      sample of 114 cases and 38% of carcinoma in situ. This data represents the first
      direct evidence of in vivo phosphorylation of CSF-1R in human breast carcinomas.

PMID- 9191056
TI  - Elevated urokinase-type plasminogen activator receptor expression in a colon
      cancer cell line is due to a constitutively activated extracellular signal
      regulated kinase-1-dependent signaling cascade.
AB  - The urokinase-type plasminogen activator receptor (u-PAR) facilitates
      extracellular matrix degradation in part by accelerating plasmin formation at the
      cell surface. We previously reported that u-PAR expression is elevated in colon
      cancer cell lines characterized by their in vitro invasive capacity. Since, u-PAR
      expression is increased by a variety of growth factors, which signal through the
      extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2), we determined if
      these mitogen-activated protein kinases (MAPKs) regulate u-PAR expression in two
      cultured colon cancer cell lines. An in-gel kinase assay showed that ERK1
      activity was considerably higher in RKO cells, which display > or = 10(5)
      receptors/cell, than the GEO cells which have approximately 10(4) urokinase
      receptors per cell. The expression of either an ERK-inactivating phosphatase
      (CL100), or a kinase-defective ERK1, decreased the activity of a u-PAR promoter
      driven CAT reporter in RKO cells. Immune complex kinase assays indicated that the
      constitutive ERK1 activity in RKO cells was largely a result of an activated
      MEK1. Further, treatment of RKO cells with a specific inhibitor (PD 098059) of
      MEK1 activation, which diminished ERK1 activity, reduced the amount of urokinase
      specifically bound to the cell surface and this was associated with reduced
      laminin degradation. The expression of a dominant negative c-Raf-1 also reduced u
      PAR promoter activity suggesting that MEK1 activation involved an activator at,
      or upstream, of this serine-threonine kinase. Transfection of the u-PAR-deficient
      GEO cells with a constitutively activated MEK1 expression construct up-regulated
      u-PAR promoter activity. Similarly treatment of GEO cells with a phosphatase
      inhibitor (sodium vanadate) caused a dose-dependent increase in ERK1 activity
      which paralleled increased cell surface binding of urokinase. Taken together,
      these data suggest that elevated u-PAR expression, in at least a sub-population
      of colon cancer, is partly a consequence of a constitutively activated ERK-1
      dependent signaling cascade.

PMID- 9191057
TI  - Relief of cyclin A gene transcriptional inhibition during activation of human
      primary T lymphocytes via CD2 and CD28 adhesion molecules.
AB  - Cyclin A transcription is cell cycle regulated and induced by cell proliferative
      signals. To understand the mechanisms underlined in this regulation in normal
      human cells, we have analysed in vivo protein-DNA interactions at the Cyclin A
      locus in primary T lymphocytes. Stimulation of purified T lymphocytes by a
      combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules
      gives rise to a long lasting proliferation in the absence of accessory cells.
      Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas
      stimulation by anti CD2 or anti CD28 alone was not effective. In vivo genomic DMS
      footprinting revealed upstream of the major transcription initiation sites, the
      presence of at least three protein binding sites, two of which were
      constitutively occupied. They bind in vitro respectively ATF-1 and NF-Y proteins.
      The third site was occupied in quiescent cells or in cells stimulated by anti CD2
      or anti CD28 alone. The mitogenic combination of anti CD2 + anti CD28 released
      the footprint as cells were committed to proliferation. Consistent with theses
      results, nuclear extracts prepared from quiescent cells formed a specific complex
      with this element, whereas extracts prepared from cells treated with anti CD2 +
      anti CD28 failed to do so after cells entered a proliferative state.

PMID- 9191058
TI  - A threshold nuclear level of the v-Rel oncoprotein is required for transformation
      of avian lymphocytes.
AB  - The net distribution of eukaryotic transcription factors between the cytoplasm
      and the nucleus provides an effective mechanism for controlling gene expression.
      We have utilized cis-acting signals for both nuclear import and nuclear export to
      experimentally manipulate the distribution of the v-Rel oncoprotein between the
      nucleus and the cytoplasm. The respective abilities of the v-Rel oncoprotein to
      localize to the nucleus in chicken embryo fibroblasts, to activate kappaB
      dependent transcription in yeast, and to transform avian lymphoid cells were each
      markedly reduced by the fusion of a cis-acting nuclear export signal onto v-Rel.
      Our results demonstrate that a threshold nuclear function of v-Rel is required
      for manifestation of its oncogenic properties. In contrast, while increased
      expression of the avian IkappaB-alpha protein was able to prevent nuclear
      localization of v-Rel in chicken embryo fibroblasts, coexpression of IkappaB
      alpha with v-Rel in the target cell for v-Rel mediated transformation did not
      reduce the ability of v-Rel to transform avian lymphoid cells or alter the
      distribution of v-Rel between the nucleus and the cytoplasm in v-Rel-transformed
      cells. Our results suggest that the ability of IkappaB-alpha to inhibit nuclear
      localization of v-Rel is affected by cell-type specific differences between
      fibroblasts and lymphoid cells.

PMID- 9191060
TI  - Somatic in frame deletions not involving juxtamembranous cysteine residues
      strongly activate the RET proto-oncogene.
AB  - Somatic RET mutations have been identified in a variable proportion (about 30
      70%) of sporadic Medullary Thyroid Carcinoma (MTC) cases. They are represented by
      the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type
      2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of
      five critical cysteine residues (exons 10 and 11) typical of MEN type 2A (MEN2A).
      An in vitro transforming activity has already been demonstrated for these
      mutations. A few different MTC somatic mutations have been reported so far whose
      biological activity has still to be tested. In this paper we report the
      identification, in two MTC tumor samples, of two interstitial deletions of 48 bp
      and 6 bp occurred in exons 10 and 11 respectively. Both were somatic heterozygous
      in frame mutations, not involving any cysteine residue. Moreover, the expression
      of a full length RET cDNA carrying one of the two deletions demonstrated a strong
      transforming capacity in NIH3T3 cells.

PMID- 9191059
TI  - K-ras modulates the cell cycle via both positive and negative regulatory
      pathways.
AB  - The effect of activated human K-ras on cell cycle proteins was studied by use of
      a stable MCF-7 transfectant expressing inducible activated K-ras under the
      control of a tetracycline (Tet)-responsive promoter. Induction of activated K-ras
      by Tet withdrawal accelerated cell growth and entry into S-phase. To understand
      the mechanism(s) by which activated K-ras exerts its effect on the cell cycle,
      expression of both cell cycle stimulatory proteins as well as cell cycle
      inhibitors was examined. Upon induction of activated K-ras, several cell cycle
      stimulators were up-regulated, including cyclins A, D3, and E, and the E2F family
      of transcription factors, which was accompanied by increased cyclin A-associated
      kinase activity and E2F transcriptional activity, respectively. Up-regulation of
      cyclin A occurred at the transcriptional level and in a serum-dependent manner.
      Furthermore, induction of activated K-ras down-regulated p27Kip1 and up-regulated
      p53. Up-regulation of p53 was correlated with enhanced p53 transactivation and
      accompanied by up-regulation of p21Waf1 and Gadd 45, two p53 effectors and
      negative cell cycle regulators. In addition, activated K-ras up-regulates bcl-2
      but has no effect on bax or bcl-x expression. Taken together, these data indicate
      that activated K-ras affects the cell cycle by modulating both positive and
      negative cell cycle regulatory pathways.

PMID- 9191062
TI  - Inhibition of Escherichia coli protein synthesis by abortive translation of phage
      lambda minigenes.
AB  - Escherichia coli mutants defective in peptidyl-tRNA hydrolase activity are unable
      to maintain bacteriophage lambda vegetative growth. Phage mutants, named bar,
      overcome the host limitation to support viral growth. Multicopy expression of
      lambda wild-type bar regions is deleterious to hydrolase-defective cells because
      it provokes arrest of protein synthesis. We noticed that the bar regions include
      minigenes whose transcripts would contain a Shine-Dalgarno-like sequence
      appropriately spaced for translation from a two codon open reading frame. To
      investigate the mechanism of bar inhibition, we asked if transcripts of the barI
      region function as mRNAs in their ribosomal interactions. We found that bar
      containing RNA associates with ribosomes, forms ternary initiation complexes,
      yields a toeprint signal, and can be removed from ribosomes by run-off
      translation, as authentic mRNA. Since bar-containing RNA has the properties of a
      messenger, we propose that its translation leads to drop-off and accumulation of
      peptidyl-tRNA in pth-defective cells. Starvation of the tRNA(s) sequestered in
      pepidyl-tRNA(s) eventually causes inhibition of protein synthesis.

PMID- 9191061
TI  - Apparent protection from instability of repeat sequences in cancer-related genes
      in replication error positive gastrointestinal cancers.
AB  - Genomic instability at simple repeated sequences has been observed in various
      types of human cancers and is considered an important mechanism in tumorigenesis.
      Alterations at microsatellite loci have been reported scattered throughout the
      genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta
      RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to
      have inactivating mutations within coding microsatellite sequences. The
      demonstration of mutations in two growth regulatory genes supports the idea that
      other regulatory genes with repeat sequences may also be targets in tumours with
      defective mismatch repair. We examined genes involved in tumour suppression, cell
      adhesion and cell cycle regulation for mutations at small repeat sequences in
      replication error positive gastrointestinal cancers. Several polymorphisms were
      found which exhibited instability, but no other instability was present in the
      regions examined.

PMID- 9191063
TI  - Leading strand specific spontaneous mutation corrects a quasipalindrome by an
      intermolecular strand switch mechanism.
AB  - Imperfect inverted repeats or quasipalindromes can undergo spontaneous, often
      complex mutational events that correct them to perfect palindromes. Two models
      that depend on the quasipalindrome providing a template for a specific mutational
      event have been described to explain this mutation: an intramolecular and an
      intermolecular strand switch model. A 17bp quasipalindrome containing a -1
      deletion within the chloramphenicol acetyl transferase (CAT) gene in plasmid pJT7
      undergoes a spontaneous +1 frameshift mutation that creates a perfect inverted
      repeat and a Cm(r) phenotype. By analyzing this mutation frequency in two
      plasmids that contain the CAT gene in either orientation with respect to the
      origin of replication, we show that the specific frameshift occurs preferentially
      in the leading strand during DNA replication. Due to the availability and
      proximity of the lagging strand template as a single strand during replication of
      the quasipalindrome in the leading but not lagging strand, we suggest that the
      specificity for the leading strand correction is due to a leading strand specific
      intermolecular strand switch rather than an intramolecular strand switch. To test
      this hypothesis, we have designed a genetic selection to detect a leading strand
      intermolecular strand switch. This selection utilizes asymmetric
      quasipalindromes, one of which contains two central stop codons. When cloned into
      the CAT gene in pJT7, reversion to Cm(r) requires inversion of the stop codons
      and addition of a +1 frameshift to correct the reading frame. The inversion of
      the central stop codons, which is predicted by an intermolecular but not an
      intramolecular strand switch, occurs concomitant with the specific correction of
      the original 17 bp quasipalindrome. Inversion of an asymmetric center can also be
      demonstrated when not under selective pressure using a quasipalindrome lacking
      central stop codons. These results are consistent with the correction of a
      quasipalindrome occurring predominantly by an intermolecular strand switch during
      replication of the leading strand.

PMID- 9191064
TI  - Characterization and divalent metal-ion dependence of in vitro selected
      deoxyribozymes which cleave DNA/RNA chimeric oligonucleotides.
AB  - By in vitro selection, a variety of catalytic DNA oligonucleotides were obtained
      which cleave chimeric oligonucleotides at a single ribonucleotide position
      embedded within a deoxyribonucleotide context in the presence or absence of
      divalent metal ions. After several cycles of selection/amplification in the
      absence and in the presence of low amounts of Mg2+ two different types of
      catalysts emerged: one type depended strongly on Mg2+ or other divalent metal
      ions, the other type performed cleavage reactions independently of Mg2+ in the
      presence of spermine. Experimental analysis of the secondary structure of some of
      the selected deoxyribozymes was carried out by chemical probing. The
      ribonucleotide in the selected catalysts is unpaired and presents the cleavage
      site to the attacking nucleophile. Our results suggest that the main selection
      criterion under metal-free conditions was a favourable arrangement of the
      attacking nucleophile and the phosphate leaving group. The cleavage rates of the
      selected divalent metal independent catalysts are within the same order of
      magnitude as the rate of metal independent substrate hydrolysis in the hammerhead
      ribozyme. One of the metal dependent catalysts showed an unexpected preference
      for Ca2+ instead of Mg2+. In this deoxyribozyme binding of Ca2+ occurred co
      operatively whereas binding of Mg2+ did not. Comparison of the secondary
      structure and reactivity of this catalyst with Mg2+ and Ca2+ suggests that here a
      special binding pocket for Ca2+ was selected. This deoxyribozyme achieved a rate
      acceleration of substrate cleavage in the order of at least 10(4) compared to the
      uncatalysed reaction performing a cleavage mechanism similar to that of the
      hammerhead or hairpin ribozyme.

PMID- 9191065
TI  - Regulation and trafficking of three distinct 18 S ribosomal RNAs during
      development of the malaria parasite.
AB  - The human malaria parasite Plasmodium vivax has been shown to regulate the
      transcription of two distinct 18 RNAs during development. Here we show a third
      and distinctive type of ribosome that is present shortly after zygote formation,
      a transcriptional pattern of ribosome types that relates closely to the
      developmental state of the parasite and a phenomenon that separates ribosomal
      types at a critical phase of maturation. The A-type ribosome is predominantly
      found in infected erythrocytes of the vertebrate and the mosquito blood meal.
      Transcripts from the A gene are replaced by transcripts from another locus, the O
      gene, shortly after fertilization and increase in number as the parasite develops
      on the mosquito midgut. Transcripts from another locus, the S gene, begins as the
      oocyst form of the parasite matures. RNA transcripts from the S gene are
      preferentially included in sporozoites that bud off from the oocyst and migrate
      to the salivary gland while the O gene transcripts are left within the oocyst.
      Although all three genes are typically eukaryotic in structure, the O gene
      transcript, described here, varies from the other two in core regions of the rRNA
      that are involved in mRNA decoding and translational termination. We now can
      correlate developmental progression of the parasite with changes in regions of
      rRNA sequence that are broadly conserved, where sequence alterations have been
      related to function in other systems and whose effects can be studied outside of
      Plasmodium. This should allow assessment of the role of translational control in
      parasite development.

PMID- 9191066
TI  - Fibrillogenesis of Alzheimer Abeta peptides studied by fluorescence energy
      transfer.
AB  - Pathogenesis of Alzheimer's disease is associated with the polymerization of the
      Abeta peptide into fibrils that accumulate to form plaques. One strategy for
      therapy is the targeting of inhibitors against fibrillogenesis; however, prior to
      the formulation of specific tactics, a thorough understanding of the
      polymerization mechanism is essential. We have applied the principle of
      fluorescence energy transfer to monitor fibrillogenesis. In theory, this method
      is capable of measuring fibrillogenesis at physiological concentrations of
      peptide. Using this assay, we have determined that: fibril formation by Abeta(9
      25) is reversible and cooperative, there are two imidazole-carboxylate salt
      bridges per monomer, monomers are in free exchange with fibrils, and the exchange
      process displays measurable kinetics.

PMID- 9191067
TI  - Solution structure of r(gaggacug):d(CAGTCCTC) hybrid: implications for the
      initiation of HIV-1 (+)-strand synthesis.
AB  - The three-dimensional solution structure of the hybrid duplex
      r(gaggacug):d(CAGTCCTC) has been determined by two-dimensional NMR, distance
      geometry (DG), restrained molecular dynamics (rMD) and NOE back-calculation
      methods. This hybrid, consisting of a purine-rich RNA strand and a pyrimidine
      rich DNA strand, is related to the polypurine (+)-strand primer formed after (-)
      strand DNA synthesis and RNase H degradation of the viral RNA strand and contains
      the site of a specific cleavage by reverse transcription (RT) RNase H at the end
      of the HIV-1 polypurine tract. This polypurine primer is an important
      intermediate in the formation of virally encoded double-stranded DNA prior to HIV
      1 retrovirus integration. The correct processing of this primer is vital in the
      life cycle of the human immunodeficiency virus type (HIV-1) retrovirus. The
      structure of the r(gaggacug):d(CAGTCCTC) hybrid, as determined in solution by
      NMR, is intermediate between canonical A-type and B-type double helices, and has
      mixed structural characteristics. It is quantitatively different from the
      previously determined solution structures of other RNA-DNA hybrids, particularly
      in the width and shape of the major groove, which is wider than the major groove
      of other hybrids and is close to the dimension of the major groove of B-type DNA
      duplexes. The structure of this hybrid duplex contains a prominent bend in the
      double helix with a magnitude and direction similar to the bend in Okazaki
      fragments. The structural features of the present duplex may explain the unique
      interactions of this sequence with HIV-1 RT during both (-)-strand and (+)-strand
      DNA synthesis.

PMID- 9191068
TI  - Protein folding simulations with genetic algorithms and a detailed molecular
      description.
AB  - We have explored the application of genetic algorithms (GA) to the determination
      of protein structure from sequence, using a full atom representation. A free
      energy function with point charge electrostatics and an area based solvation
      model is used. The method is found to be superior to previously investigated
      Monte Carlo algorithms. For selected fragments, up to 14 residues long, the
      lowest free energy structures produced by the GA are similar in conformation to
      the corresponding experimental structures in most cases. There are three main
      conclusions from these results. First, the genetic algorithm is an effective
      method for searching amongst the compact conformations of a polypeptide chain.
      Second, the free energy function is generally able to select native-like
      conformations. However, some deficiencies are identified, and further development
      is proposed. Third, the selection of native-like conformations for some protein
      fragments establishes that in these cases the conformation observed in the full
      protein structure is largely context independent. The implications for the nature
      of protein folding pathways are discussed.

PMID- 9191069
TI  - The domains in gammaB-crystallin: identical fold-different stabilities.
AB  - gammaB-crystallin from vertebrate eye lens is an all beta-sheet two-domain
      protein with a high degree of intrachain symmetry. Its N and C-terminal domains
      show high levels of sequence similarity and structural identity. In natural
      gammaB-crystallin, the domains fold independently. The recombinantly expressed
      isolated domains are stable monomeric proteins, which do not associate
      spontaneously to form a gammaB-like dimer. In contrast to their identical folding
      topology, the two domains obviously follow different folding mechanisms. While
      the two-state model is valid for the C-terminal domain, the folding behaviour of
      the N-terminal domain is more complex. The stability of the C-terminal domain is
      strongly dependent on pH. At pH 2, the C-terminal domain in its isolated form is
      significantly less stable than within the gammaB-molecule. In contrast, the
      isolated N-terminal domain does not differ in its stability from the N-terminal
      domain in wild-type gammaB-crystallin. The strongly decreased stability of the C
      terminal domain at acid pH allowed a dissection of the intrinsic stabilities of
      the domains and their interactions in gammaB-crystallin. At pH 2, domain
      interactions contribute -16 kJ/mol to the overall stability of gammaB-crystallin.

PMID- 9191070
TI  - A structural and functional comparison of staphylococcal enterotoxins A and C2
      reveals remarkable similarity and dissimilarity.
AB  - Staphylococcal enterotoxins and toxic shock syndrome toxin-1 are known as
      superantigens due to their ability to activate a large number of T-cells by
      crosslinking the major histocompatibility complex class II molecules with the T
      cell receptor. Although superantigens seem to act by a common mechanism, they
      vary in many of their specific interactions and biological properties. A
      structural comparison of staphylococcal enterotoxins A and C2, members of the
      staphylococcal superantigens, has shown large conformational differences at the
      putative TcR interaction site (loops between alphaN-alpha2, alpha4-beta9 and
      beta10-alpha5 in staphylococcal enterotoxin A) that could explain the variability
      in their T-cell receptor specificity. A common Zn2(+)-binding site was identified
      in both staphylococcal enterotoxin A and C2 that is superimposable but differs
      somewhat in its coordination geometry between the two molecules.

PMID- 9191071
TI  - Analysis of protein-protein interactions and the effects of amino acid mutations
      on their energetics. The importance of water molecules in the binding epitope.
AB  - A modeling analysis has been conducted to assess the determinants of binding
      strength and specificity for three crystal complexes; the anti-hen egg white
      lysozyme antibody D1.3 complexed with hen egg white lysozyme (HEL), the D1.3
      antibody complexed with the anti-lysozyme antibody E5.2, and barnase complexed
      with barstar. The strengths of individual binding components within these
      interfaces are evaluated using a model of binding free energy that is based on
      pairwise surface preferences. In all cases the energetics of binding are
      dominated by a relatively small number of interfacial residues that define the
      binding epitope. A precise geometric arrangement of these residues was not found;
      they were either localized to one region, or distributed throughout the binding
      interface. Surprisingly, interfacial crystal water molecules were calculated to
      contribute around 25% of the total calculated binding strength. Theoretical
      alanine mutations were completed by atomic deletions of the wild-type complexes.
      Strong correlations were observed between the calculated changes in binding free
      energy (deltadeltaG(calculated)) and the experimental values
      (deltadeltaG(observed)) for all but three of the 30 single residue mutations in
      the D1.3-HEL, D1.3-E5.2 and barnase-barstar systems and for all of the double
      mutations in the barnase-barstar system. This analysis finds that the observed
      differences in binding strength are consistent with a model that accounts for the
      changes in binding energy from the direct contacts between each member of the
      complex and indirect changes due to released crystallographic water molecules
      that are near the mutation site. The observed energy changes for double mutations
      in the barnase-barstar system is fully accounted for by considering water
      molecules bound jointly by each member of the complex.

PMID- 9191072
TI  - Opioid receptor expression in the rat gastrointestinal tract: a quantitative
      study with comparison to the brain.
AB  - The present study was undertaken to analyze the expression of two opioid receptor
      genes (mu and kappa) in different gastrointestinal regions of the rat. A
      combination of mRNA quantification and immunohistochemical visualization was used
      to characterize their expression. Using naive animals, RNA was extracted from
      tissues and used in RNase protection assays: both receptor mRNAs were expressed
      in all investigated areas but displayed different expression profiles across the
      various regions of the digestive tract. Stomach and proximal colon appeared to
      have the highest expression levels of both receptors, whereas the lowest
      expression levels were found in the duodenum. Expression levels for both
      receptors were always lower in the gastrointestinal tract compared to the brain.
      However, the kappa-receptor expression in the proximal colon represented 40% of
      the amount found in the brain, which is almost 4 times as high as the respective
      mu-receptor expression. In contrast to smooth muscle cells, myenteric plexus
      perikarya of the rat stomach and colon were immunoreactive with antibodies raised
      against the C-termini of both kappa- and mu-opioid receptors. Numerous nerve
      fibers were also immunoreactive for both mu- and kappa-receptors and distributed
      in the longitudinal and circular muscle layers. Small perikarya immunoreactive
      for mu-receptor were localized around the myenteric plexus and at the submucosal
      border of the circular muscle, whereas only few perikarya were immunoreactive for
      the kappa-receptor. We conclude that at least in rat stomach and colon, mu- and
      kappa-opioid receptors may directly control neuronal communication but seem to
      have no direct influence on smooth muscle cells.

PMID- 9191073
TI  - Differential proopiomelanocortin gene expression in the medial basal hypothalamus
      of rats during pregnancy and lactation.
AB  - Hypothalamic proopiomelanocortin (POMC) gene expression was determined using in
      situ hybridization histochemistry (ISHH) during pregnancy and lactation in rats
      with and without prior reproduction experience. POMC mRNA levels in the arcuate
      nucleus were compared between primigravid (first pregnancy) and multigravid
      (second pregnancy) and primiparous and multiparous lactating rats, and between
      these groups and age-matched, regularly cycling, nulliparous females in diestrus.
      Hybridizations were performed using a digoxigenin-labeled riboprobe complementary
      to 837 bp of the POMC gene. The number of cells expressing POMC mRNA in the
      arcuate nucleus decreased in primiparous rats on day 12 of lactation when
      compared with the number of POMC cells in the arcuate nucleus of nulliparous rats
      in diestrus. In addition, the number of cells expressing POMC mRNA in multigravid
      animals was significantly less than in the primigravid group on days 7 and 21 of
      pregnancy, and on day 12 of lactation in primiparous animals. Repeated
      reproductive experience affected the number of POMC mRNA positive cells; there
      were fewer cells expressing POMC mRNA in the multigravid females on day 7 of
      pregnancy and an increase in the number of POMC cells in the multiparous group on
      day 12 of lactation compared to the primiparous animals. Optical density
      measurements revealed a significant increase in reaction product in the labeled
      cells on all days of pregnancy compared with virgin females in diestrus and a
      significant decrease in reaction product on day 12 of lactation in the
      multiparous group. The results of the present study indicate that POMC gene
      expression changes across pregnancy and lactation and that repeated reproductive
      experience has long-term, possibly permanent, effects on the endogenous opioid
      system.

PMID- 9191074
TI  - Extensive splice variation and localization of the EHK-1 receptor tyrosine kinase
      in adult human brain and glial tumors.
AB  - EHK-1 is a neuronal ELK-related receptor tyrosine kinase which interacts with
      multiple, membrane-anchored ligands. Recent experiments have suggested a role for
      some of these ligands in the formation of neuronal pathways. Here, we report the
      isolation of human EHK-1 cDNAs and the localization of the human EHK-1 gene to
      chromosome 4q12. Six EHK-1 mRNA splice variants encoding cell-surface receptors
      with catalytic domains were identified in adult human brain where a 120-kDa EHK-1
      protein predominates. Immunohistochemistry for EHK-1 reveals a dendritic staining
      pattern in cortical neurons and cerebellar Purkinje cells and a marked
      accumulation of EHK-1 in the somas of pyramidal neurons within the cortex and
      hippocampus. Interestingly, we have identified lineage aberrant expression of EHK
      1 in a number of human gliomas. In addition to functions during development, EHK
      1 may be involved in the maintenance of the adult nervous system and contribute
      to glioma development.

PMID- 9191075
TI  - Chronic food restriction and streptozotocin-induced diabetes differentially alter
      prodynorphin mRNA levels in rat brain regions.
AB  - It was previously reported that chronic food restriction and streptozotocin
      induced diabetes lead to brain region-specific changes in levels of Prodyn
      derived peptides. These changes parallel behavioral adaptations that are reversed
      by opioid antagonists. In the present study, effects of food restriction and
      diabetes on Prodyn gene expression were measured in rat brain regions using a
      quantitative solution hybridization mRNA assay. Picogram amounts of Prodyn mRNA
      were determined in extracts of five brain regions. The highest density of Prodyn
      mRNA was observed in extracts of nucleus accumbens (4.68 pg/microg total RNA),
      bed nucleus of the stria terminalis (4.18 pg/microg), and in caudate nucleus
      (3.51 pg/microg). Lower levels were observed in the lateral hypothalamus (1.87
      pg/microg) and central nucleus of the amygdala (1.22 pg/microg). Food restriction
      and diabetes both markedly increased the levels of Prodyn mRNA in the central
      amygdala (163% and 93%, respectively). Levels in the lateral hypothalamus were
      also increased (35% and 29%, respectively), though only the food-restriction
      effect was statistically significant. Neither treatment altered prodynorphin mRNA
      levels in the caudate nucleus, nucleus accumbens or bed nucleus of the stria
      terminalis. These results suggest that dynorphin neurons in central amygdala and
      lateral hypothalamus may be involved in behavioral or physiological adaptations
      to sustained metabolic need.

PMID- 9191077
TI  - Aging-related regulation of myo-inositol 1,4,5-trisphosphate signal transduction
      pathway in the rat striatum.
AB  - To determine the effects of the aging process on the regulation of
      phosphoinositide signal transduction pathway, inositol 1,4,5-trisphosphate and
      inositol 1,4,5-trisphosphate receptor-associated parameters were examined in the
      striatum of brains removed from young (3 months), adult (12 months) and senescent
      (25 months) male Fischer 344 rats. Inositol 1,4,5-trisphosphate content was
      significantly increased (P < or = 0.01) at 25 months of age compared to 3 and 12
      months. No age-related differences in phosphatidylinositol 4,5-bisphosphate
      hydrolysis were found in striatal slices after stimulation with trans-(1S,3R)-1
      aminocyclopentane-1,3-dicarboxylate, a metabotropic glutamatergic receptor
      agonist. Phosphatidylinositol 4,5-bisphosphate hydrolysis following stimulation
      with (R,S)-alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid, a
      glutamatergic/quisqualate agonist, showed a significantly increased accumulation
      of net [3H]inositol 1,4,5-trisphosphate in senescent striatum whereas the
      muscarinic cholinergic agonist carbachol induced highest response in the young
      striatum. In each case, agonist-stimulated response was significantly reduced in
      the presence of the receptor-associated antagonist. The density of inositol 1,4,5
      trisphosphate receptor in the particulate membranes derived from 12- and 25-month
      old rats was decreased (P < 0.01) compared to that from young rats. Binding
      affinity of inositol 1,4,5-trisphosphate receptor for [3H]inositol 1,4,5
      trisphosphate was increased (P = 0.05) only at 25 months of age when compared
      with 3 months of age. Incubation of partially purified inositol 1,4,5
      trisphosphate receptor with striatal cytosol in the presence of Ca2+ showed an
      age-dependent susceptibility to proteolytic degradation of this receptor that was
      completely inhibited by calpain I inhibitor peptide. Paradoxically, the quantity
      of inositol 1,4,5-trisphosphate receptor mRNA-encoding transcripts was increased
      (P < or = 0.01) at 25 months of age, suggesting an age-dependent change in either
      transcriptional rate, stability or processing of inositol 1,4,5-trisphosphate
      receptor mRNAs in the striatum. The activity of inositol 1,4,5-trisphosphate3
      kinase decreased (P < or = 0.01) with age whereas the activity of soluble
      inositol 1,4,5-trisphosphate 5-phosphatase was highest at 3 months but
      significantly decreased at 12 months of age. However, the activity of inositol
      1,4,5-trisphosphate 5-phosphatase remained unchanged between 12 and 25 months of
      age, suggesting possible developmental modulation of the activity of the enzyme.
      Taken together with the established 'cross-talk' between signal transduction
      systems, the present data suggest that molecular/cellular changes in striatal
      inositol 1,4,5-trisphosphate/Ca2+ signal transduction pathway along with neuronal
      cell loss may contribute to aging-related decrease in striatal functioning.

PMID- 9191076
TI  - Deprenyl induces the tyrosine hydroxylase enzyme in the rat dopaminergic
      nigrostriatal system.
AB  - Chronic treatment of aged rats with deprenyl prevents age-induced protein
      oxidation in substantia nigra and protects tyrosine hydroxylase (TH) enzyme
      against inactivation [11]. With these precedents, we treated adult rats with
      deprenyl for 3 weeks in order to get further insight in the mechanism by which
      deprenyl exerts such actions. After completing the treatment, dopamine (DA)
      levels markedly increased in both striatum and substantia nigra while levels of
      the acid DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic
      acid (HVA), decreased in the two brain areas, thus proving MAO-inhibiting
      properties of the treatment. We then studied the cellular expression of TH mRNA
      by in situ hybridization. Following treatment with deprenyl, levels of TH mRNA
      were significantly higher in individual dopaminergic nigral cell bodies than in
      those of control rats (+74%). Western blotting analysis of TH enzyme amount
      revealed a positive effect of the treatment in both the terminal field (+44%) and
      the cell body region (+31%). This correlation between TH mRNA and amount was also
      extended to TH enzyme activity in the two brain areas studied, which
      significantly increased in striatum (+57%) and substantia nigra (+35%) following
      deprenyl treatment. Taken together, our results clearly suggest a TH-inducing
      effect of deprenyl in the dopaminergic nigrostriatal system, which seems to be
      independent of its protective action against oxidative stress described
      previously. These results expand our knowledge about the beneficial effect of
      deprenyl in the therapy of Parkinson's disease.

PMID- 9191078
TI  - Regional and cellular expression patterns of four K+ channel mRNAs in the adult
      rat brain.
AB  - Potassium (K+) channels are involved in the modulation and fine tuning of the
      excitable properties of neurons and glia in the nervous system. In the present
      report, in situ hybridization histochemistry was used to determine the regional
      and cellular distribution patterns in the adult rat brain of four mRNAs encoding
      subunits of voltage-gated K+ channels. These are Kv1.1, Kv1.6, K13 and IK8. All
      K+ channels examined showed distinct yet overlapping expression patterns.
      Expression of Kv1.1 mRNA was high in cells of certain motor-related structures of
      the brainstem. Kv1.6 mRNA expression was observed in cerebellar Purkinje cells
      and in various olfactory and amygdaloid structures. K13 was the only mRNA
      expressed in both neuronal and non-neuronal cell populations, including the cells
      of choroid plexus and pia. IK8 expression was observed only in the forebrain
      structures. In many brain regions, mRNAs for Kv1.1 and Kv1.6, both encoding K+
      channel subunits belonging to the Shaker subfamily, were co-expressed, a
      necessary condition for heteromultimer formation.

PMID- 9191079
TI  - Olfactory memory and maternal behaviour-induced changes in c-fos and zif/268 mRNA
      expression in the sheep brain.
AB  - In sheep maternal behaviour and the formation of the selective olfactory,
      ewe/lamb bond are induced by feedback to the brain from stimulation of the vagina
      and cervix during parturition. In the present study, we have used in situ
      hybridization histochemistry to quantify changes in cellular expression of two
      immediately-early genes, c-fos and zif/268, in order to identify activated brain
      regions during the induction of maternal behaviour and olfactory bonding as well
      as regions where plastic changes are occurring during with the formation of the
      olfactory memory associated with bonding. Three different treatment groups were
      used. One group gave birth normally, became maternal and were allowed to interact
      with their lambs for 30 min. A second group received exogenous treatment with
      oestradiol and progesterone to induce lactation and then received a 5-min period
      of artificial stimulation of the vagina and cervix (VCS) which reliably induces
      maternal behaviour but could not interact with lambs. A final control group
      received exogenous hormone treatment but no VCS or interaction with lambs.
      Compared to the control group, post-partum animals and animals that had received
      VCS showed increased c-fos expression in a number of cortical regions (cingulate,
      entorhinal and somatosensory), the mediodorsal thalamic nucleus and the lateral
      habenula, the limbic system (bed nucleus of the stria terminalis, lateral septum,
      medial arnygdala, dentate gyrus and the CA3 region of the hippocampus) and the
      hypothalamus (medial preoptic area, mediobasal hypothalamus, paraventricular
      nucleus, supraoptic nucleus and periventricular complex). The group that gave
      birth and had contact with their lambs for 30 min had significantly enhanced c
      fos mRNA expression in the cingulate cortex compared to those receiving VCS and
      additionally showed significantly increased c-fos mRNA expression in olfactory
      processing regions (olfactory bulb, piriform cortex and orbitofrontal cortex).
      Expression of zif/268 was significantly increased in the entorhinal cortex,
      orbitofrontal cortex and dentate gyrus of the parturition group compared to
      either the control or the VCS alone groups. These results show a clear
      differentiation between neural substrates controlling the expression of maternal
      behaviour and those involved in the olfactory memory process associated with
      selective recognition of offspring although at the level of the hippocampus and
      cingulate cortex there may be some degree of overlap. Alterations in zif/268 at
      tertiary processing sites for olfactory information (orbitofrontal cortex) and
      the entorhinal cortex and dentate gyrus may reflect plastic changes occurring
      during the early stages of olfactory memory formation.

PMID- 9191080
TI  - Effects of ethanol on muscarinic receptor-stimulated c-fos expression in human
      neuroblastoma cells.
AB  - The effect of ethanol exposure on muscarinic receptor-stimulated expression of c
      fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced
      carbachol-stimulated c-fos mRNA expression, analyzed with Northern blot, and
      Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre
      incubation with muscarinic antagonists or the protein kinase C inhibitor
      GF109203X demonstrated that, in both control and ethanol-treated cells, carbachol
      induced c-fos expression was mediated via muscarinic M1 receptors and to a large
      extent through protein kinase C. However, phorbol ester-induced c-fos expression
      was unaffected in ethanol-treated cells. Acute exposure to ethanol caused a
      suppression of both carbachol- and phorbol ester-stimulated c-fos expression.
      These results demonstrate that muscarinic receptor-stimulated gene expression is
      sensitive to both acute and long-term ethanol exposure.

PMID- 9191081
TI  - An anti-chi-1 antibody recognizes a heavily glycosylated protein in rat brain.
AB  - The chi(-1) subunit is a recently identified member of a new class of the
      ionotropic glutamate receptor family that attenuates NMDA receptor current. We
      have generated a polyclonal C-terminal antibody to the chi(-1) subunit which
      recognizes a 135-kDa protein in membranes prepared from chi(-1) transfected HEK
      293 cells and in rat brain. In the post-natal day 7 (P7) rat brain, Western blot
      analysis revealed a 135-kDa band in the thalamus and cortex but not the striatum,
      cerebellum or peripheral tissues. De-glycosylation of the chi(-1) subunit in both
      transfected cell lines and in the brain reduced the 135-kDa band to 110 kDa, near
      the predicted molecular weight of the chi(-1) subunit. These studies demonstrate
      the chi(-1) subunit is expressed as a glycosylated protein subunit in a
      distribution that parallels that observed for chi(-1) mRNA by in situ
      hybridization.

PMID- 9191082
TI  - Transgene expression of plasmid DNAs directed by viral or neural promoters in the
      rat brain.
AB  - The use of circular plasmid DNA may be an alternative method for the transfer of
      genes into the brain and is presumably easier to use than other vectors, such as
      viruses or genetically engineered cells. The effectiveness and time course of the
      expression of a reporter gene (LacZ), directed by appropriate promoters, was
      studied after stereotaxic injection of naked plasmid DNAs into the rat thalamus,
      cortex or cerebellum. The efficiencies of three different promoters, the human
      cytomegalovirus (HCMV) promoter and the glial fibrillary acidic protein (GFAP)
      and neuron-specific enolase (NSE) promoters (specific for astrocytes and neurons,
      respectively) to drive reporter gene expression were compared. Efficient
      expression of beta-gal, detected by X-gal histochemistry or immunochemistry,
      required the use of 50 microg of DNA and was detectable as early as 48 h after
      injection. Expression increased until day 8, remained stable until day 15, then
      decreased over 2 months, probably as a result of non-specific degradation of the
      plasmids within the transfected cells rather than from specific down-regulation
      of promoters, as the same time course was seen with all three promoters tested.
      Depending on the promoter used (GFAP or NSE), LacZ was preferentially expressed
      within astrocytes or neurons, respectively. The GFAP promoter was found to be as
      efficient as the HCMV promoter, possibly due to the reactive gliosis induced by
      plasmid injection which is known to up-regulate GFAP expression.

PMID- 9191083
TI  - Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid
      receptor binding and mRNA levels in several rat brain regions.
AB  - Previous data showed the development of tolerance to a variety of pharmacological
      effects of plant and synthetic cannabinoids when administered chronically. This
      tolerance phenomenon has been related both to enhancement of cannabinoid
      metabolism and, in particular, to down-regulation of brain CB1 cannabinoid
      receptors, although this has been only demonstrated in extrapyramidal areas. In
      the present study, we have tested, by using autoradiographic analysis of CB1
      receptor binding combined with analysis of CB1 receptor mRNA levels in specific
      brain regions by Northern blot, whether the reduction in binding levels of CB1
      receptors observed in extrapyramidal areas after a chronic exposure to delta9
      tetrahydrocannabinol (delta9-THC), also occurs in most brain areas that contain
      these receptors. Results were as follows. The acute exposure to delta9-THC
      usually resulted in no changes in the specific binding of CB1 receptors in all
      brain areas studied, discarding a possible interference in binding kinetic of the
      pre-bound administered drug. The only exceptions were the substantia nigra pars
      reticulata and the cerebral cortex, which exhibited decreased specific binding
      after the acute treatment with delta9-THC presumably due to an effect of the pre
      bound drug. The specific binding measured in animals chronically (5 days) exposed
      to delta9-THC decreased ranging from approximately 20 up to 60% of the specific
      binding measured in control animals in all brain areas. Areas studied included
      cerebellum (molecular layer), hippocampus (CA1, CA2, CA3, CA4 and dentate gyrus),
      basal ganglia (medial and lateral caudate-putamen and substantia nigra pars
      reticulata), limbic nuclei (nucleus accumbens, septum nucleus and basolateral
      amygdaloid nucleus), superficial (CxI) and deep (CxVI) layers of the cerebral
      cortex and others. There were only two brain regions, the globus pallidus and the
      entopeduncular nucleus, where the specific binding for CB receptors was unaltered
      after 5 days of a daily delta9-THC administration. In addition, we have analyzed
      the levels of CB1 receptor mRNA in specific brain regions of animals chronically
      exposed to delta9-THC, in order to correlate them with changes in CB1 receptor
      binding. Thus, we observed a significant increase in CB1 receptor mRNA levels,
      but only in the striatum, with no changes in the hippocampus and cerebellum. In
      summary, CB1 receptor binding decreases after chronic delta9-THC exposure in most
      of the brain regions studied, although this was not accompanied by parallel
      decreases in CB receptor mRNA levels. This might indicate that the primary action
      of delta9-THC would be on the receptor protein itself rather than on the
      expression of CB1 receptor gene. In this context, the increase observed in mRNA
      amounts for this receptor in the striatum should be interpreted as a presumably
      compensatory effect to the reduction in binding levels observed in striatal
      outflow nuclei.

PMID- 9191084
TI  - Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in the
      mesencephalic trigeminal nucleus of the rat after transsection of the masseteric
      nerve.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the VIP
      (vasoactive intestinal polypeptide) family of peptides, has been demonstrated in
      neurons of the sensory system. PACAP expression of these neurons is sensitive to
      nerve damages such as nerve crush or axotomy. In the present study, PACAP
      expression in the mesencephalic trigeminal nucleus of the rat was examined after
      transsection of the main trunk of the masseteric nerve. The primary sensory
      neurons of the nucleus are considered to have purely proprioceptive functions. By
      quantitative in situ hybridization using a PACAP [35S]cRNA probe, an increase in
      PACAP mRNA was observed on the side ipsilateral to transsection already after 3 h
      and the expression reached a peak 24 h after surgery after which the levels
      gradually decreased during the next 14 days. A low and constant expression of
      PACAP mRNA could be seen on the side contralateral to transsection. PACAP
      immunoreactivity was demonstrated on the ipsilateral side after 18 h, using a
      specific monoclonal PACAP antibody. Co-existence of PACAP with NPY and galanin
      was demonstrated 7 days after transsection. Analysis of the masseteric nerve by
      radioimmunoassay on transsected and normal nerve stumps revealed an increase of
      PACAP-38 immunoreactivity in the nerve proximal to the transsection compared to
      the normal side (15.3 vs. 6.1 pmol/g wt). The results suggest that PACAP has a
      role in the early phase of adaptation to nerve injury in the proprioceptive
      neurons.

PMID- 9191085
TI  - Nerve growth factor mRNA stability is controlled by a cis-acting instability
      determinant in the 3'-untranslated region.
AB  - Nerve growth factor (NGF) mRNA is rapidly degraded in many non-neuronal cell
      types with a half-life of between 30 and 60 min. Similar to other short-lived
      mRNAs the 3'-untranslated region (3'-UTR) of the NGF mRNA contains a short AU
      nucleotide-rich sequence. To implicate this region as a cis-acting determinant of
      NGF mRNA instability, expression vectors containing NGF cDNA with and without the
      3'-UTR, and vectors containing only the 3'-UTR were constructed and used in cell
      transfection experiments. Transfection of HEK293 or NIH3T3 cells with these
      expression vectors followed by measurement of NGF mRNA half-life indicated that
      NGF mRNA without the AU-rich 3'-UTR was approximately 3-fold more stable than NGF
      mRNA containing the 3'-UTR. Similar results were seen in a polysome-based cell
      free RNA decay assay using NGF mRNA with and without the 3'-UTR prepared from
      transfected cells. Addition of a short RNA containing the AU-rich 3'-UTR to the
      cell-free RNA decay system prolonged the half-life of the full-length NGF mRNA,
      suggesting competition between these two RNA species for polysome-associated
      factors which degrade the NGF mRNA. Moreover, transfection of HEK293 or
      astroglial cells with vectors designed to express only the AU-rich region of the
      3'-UTR resulted in enhanced expression of NGF mRNA. The results indicate that the
      3'-UTR of the NGF mRNA contains a cis-acting instability determinant which,
      perhaps by interacting with trans-acting RNA-binding proteins, controls the rate
      of NGF mRNA turnover.

PMID- 9191086
TI  - Comparison of the effects of an ampakine with those of methamphetamine on
      aggregate neuronal activity in cortex versus striatum.
AB  - The present study used in situ hybridization to c-fos mRNA to compare the effects
      of an 'ampakine' (a positive modulator of AMPA type glutamate receptors) with
      those of methamphetamine on the balance of aggregate neuronal activity in the
      cortex versus striatum. Methamphetamine (n = 11) induced a marked increase in c
      fos mRNA in the dorsomedial quadrant of the striatum and a 21% smaller, but still
      reliable, increase in the ventrolateral quadrant. The drug also elevated c-fos
      mRNA levels in the ventral and medial segments of the orbitofrontal cortex but
      had no detectable effects in motor and somatosensory neocortices. The ampakine (n
      = 11) caused a near inverse pattern of changes; i.e. a sizable increase in
      somatosensory labeling and a significant decrease in striatal labeling with
      statistically insignificant effects in motor and orbitofrontal cortex. Within-rat
      cortical and striatal values were correlated in both the vehicle (n = 11) and
      ampakine groups, and appropriate comparisons established that the ampakine caused
      27-55% increases in the ratio of cortical to striatal labeling. These results are
      in accord with the idea that facilitation of glutamatergic transmission has
      'network level' effects that are opposite in nature to those resulting from
      enhanced dopaminergic transmission. The potential relevance of ampakines alone or
      in conjunction with dopamine antagonists for the treatment of schizophrenia is
      discussed.

PMID- 9191087
TI  - Expression and functional role of the Id HLH family in cultured astrocytes.
AB  - The Id family of helix-loop-helix factors (Id1, Id2, and Id3) expressed in many
      types of cells has been reported to negatively regulate myoblast differentiation
      and is required for G1/S progression of arrested fibroblasts. Our previous
      studies have indicated that Id1, Id2, and Id3 mRNA expression appear in the
      subventricular zone of 1-day-old rat brains. At later ages, Id3 mRNA was only
      expressed in astrocytes. We now report that Id1 and Id3 mRNA expression increased
      in astrocytes during the first hour of serum stimulation. Subsequently, the Id1
      and Id3 mRNA levels gradually declined to basal level as observed in cultures
      without serum stimulation. However, there was no significant difference in Id2
      mRNA expression between serum-treated and control astrocyte cultures within 1 h
      of serum induction. In addition, a strong nuclear immunostaining for Id2 and Id3
      proteins was observed 24 h after serum stimulation. This observation is
      consistent with our results that show an increase in Id2 and Id3 protein levels
      following 24 h serum induction. Furthermore, DNA synthesis in FCS-stimulated
      astrocytes was blocked by antisense oligonucleotides against Id3 mRNA. The
      addition of Id3 antisense oligonucleotides caused approximately 50% reduction in
      Id3 mRNA and protein levels when compared to that in sense-treated cultures. The
      results indicate that the inhibition of DNA synthesis in FCS-stimulated
      astrocytes is due to a decrease in Id3 levels by the antisense. These
      observations suggest that Id3 may play an important role in the regulation of
      astrocyte proliferation.

PMID- 9191088
TI  - NGFI-A expression in the rat brain after sleep deprivation.
AB  - The effects of total sleep deprivation (SD) on the expression of the immediate
      early gene NGFI-A were studied in the rat brain by in situ hybridization. Rats
      were manually sleep-deprived for 3, 6, 12 and 24 h starting at light onset (08:00
      h) and for 12 h starting at dark onset (20:00 h). SD performed during the day
      induced a marked increase in NGFI-A mRNA levels with respect to sleep controls in
      many cerebrocortical areas and caudate-putamen, which was most evident after 6 h
      SD. A decrease was seen in hippocampus and thalamus, particularly after 12 h SD.
      Rats sleep-deprived for 12 h during the night showed an increase in NGFI-A
      expression in some cortical areas while rats sleep-deprived for 24 h showed few
      changes with respect to controls. The pattern of NGFI-A expression after forced
      wakefulness showed some differences from that observed after spontaneous
      wakefulness [M. Pompeiano, C. Cirelli and G. Tononi, Immediate early genes in
      spontaneous wakefulness and sleep: expression of c-fos and NGFI-A mRNA and
      protein, J. Sleep Res., 3 (1994) 80-96]. These observations are discussed with
      respect to the functional consequences of wakefulness in specific brain areas.

PMID- 9191089
TI  - Elevated expression of glutathione peroxidase in PC12 cells results in protection
      against methamphetamine but not MPTP toxicity.
AB  - In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system
      which may be due in part to the generation of reactive oxygen species (ROS). The
      resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the
      effects of both MPTP and MA suggests the involvement of superoxide in the
      resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to
      hydrogen peroxide, which itself can cause cellular degeneration by reacting with
      free iron to produce highly reactive hydroxyl radicals resulting in damage to
      proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also
      been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed
      during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA
      induced dopamine release from synaptic vesicles within nerve terminals. To test
      whether hydrogen peroxide is an important factor in the toxicity of either of
      these two neurotoxins, we created clonal PC12 lines expressing elevated levels of
      the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation
      of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid
      peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx
      also appeared to prevent decreases in transport-mediated dopamine uptake produced
      via MA administration as well as to attenuate toxin-induced cell loss as measured
      by either MTT reduction or LDH release. Our data, therefore, suggest that
      hydrogen peroxide production likely contributes to MA toxicity in dopaminergic
      neurons.

PMID- 9191090
TI  - Pharmacological modulation of Alzheimer's beta-amyloid precursor protein levels
      in the CSF of rats with forebrain cholinergic system lesions.
AB  - Abnormal deposition and accumulation of Alzheimer's amyloid beta-protein (A beta)
      and degeneration of forebrain cholinergic neurons are among the principal
      features of Alzheimer's disease. Studies in rat model systems have shown that
      forebrain cholinergic deficits are accompanied by induction of cortical beta
      amyloid precursor protein (beta-APP) mRNAs and increased levels of secreted beta
      APP in the CSF. The studies reported here determined whether the CSF levels of
      secreted beta-APP could be altered pharmacologically. In different experiments,
      rats with lesions of the forebrain cholinergic system received injections of
      vehicle, a muscarinic receptor antagonist scopolamine, or one of two
      cholinesterase inhibitors - diisopropyl phosphorofluoridate (DFP) or phenserine.
      Scopolamine was administered to determine whether the levels of beta-APP in the
      CSF could be increased by anticholinergic agents. The cholinesterase inhibitors
      were administered to determine whether the forebrain cholinergic system lesion
      induced increases in CSF beta-APP could be reduced by cholinergic augmentation.
      Scopolamine administration led to a significant increase in the CSF levels of
      secreted beta-APP in sham-lesioned rats. Phenserine, a novel, reversible acetyl
      selective cholinesterase inhibitor, significantly decreased the levels of
      secreted beta-APP in the CSF of forebrain cholinergic system-lesioned rats
      whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect
      CSF levels of secreted beta-APP. These results suggest that the levels of
      secreted beta-APP in the CSF can be pharmacologically modulated but that this
      modulation is dependent upon the status of the forebrain cholinergic system and
      the pharmacological properties of the drugs used to influence it.

PMID- 9191091
TI  - Distribution and polysome association of full-length and 3' truncated
      preproenkephalin mRNA in the guinea-pig brain.
AB  - The preproenkephalin gene is expressed in the mammalian central and peripheral
      nervous system as well as in other tissues, including the pituitary, adrenal
      medulla, lymphocytes, and reproductive and digestive systems. In the guinea-pig
      brain, preproenkephalin mRNA transcripts are cleaved at a specific site located
      in the 3' untranslated region. We used a solution hybridization RNAse protection
      assay to measure total levels of preproenkephalin mRNA and to determine the ratio
      of full-length to truncated forms in the pituitary and 12 brain regions of the
      guinea-pig. The overall distribution of preproenkephalin mRNA was found to be
      similar to that observed in other species in which it has been measured, with the
      highest levels of expression located in the caudate putamen and nucleus
      accumbens. The 3' truncated form was found throughout the brain in varying levels
      depending on the region. In nine regions examined, levels of the shorter form
      varied between 35 and 59% of total preproenkephalin mRNA content. The cerebellum
      and pons/medulla contained 17% each. In the pituitary, the only non-brain tissue
      studied, the truncated form constituted only 4% of total preproenkephalin mRNA.
      No correlation between absolute mRNA levels and the distribution between the two
      forms was observed. Both the full-length and 3' truncated mRNA forms were
      associated with polysomes isolated from the guinea-pig caudate putamen by sucrose
      density gradient centrifugation, suggesting that both mRNA forms may be actively
      translated. The distribution between the two forms, however, was different on the
      polysomal and dissociated monosomal gradients: the polysomal preproenkephalin
      mRNA contained a higher proportion of the full-length form whereas the monosomal
      fractions contained slightly more of the truncated form. This discontinuity in
      the amount of the two forms between polysomal and non-polysomal mRNA may suggest
      that the full-length form is more readily incorporated into polysomes.

PMID- 9191092
TI  - Induction of FOS and JUN proteins during focal epilepsy: congruences with and
      differences to [14C]deoxyglucose metabolism.
AB  - fos and jun belong to multigene families coding for transcription factors. These
      cellular immediate-early genes (IEGs) are thought to be involved in coupling
      neuronal excitation to changes of target gene expression. Immunocytochemistry
      with specific antisera was used to assess regional levels of five IEG-encoded
      proteins (c-FOS, FOS B, c-JUN, JUN B and JUN D) in a rat model of penicillin
      induced focal epilepsy. To assess whether brain regions with post-ictal de novo
      transcription factor synthesis correspond to those areas with increased glucose
      metabolism, IEG expression patterns were compared with [14C]deoxyglucose
      autoradiography performed in a subset of animals. The results demonstrated marked
      induction of c-FOS, FOS B, c-JUN and JUN B but not JUN D in the cortical
      epileptic focus. Thereby, individual IEG-encoded proteins exhibited differential
      temporal and spatial expression patterns. Within the epileptic focus, IEG
      expression correlated with increased glucose metabolism. In contrast, IEG
      induction was not observed in brain areas distant from the epileptic focus that
      also demonstrated increased glucose metabolism, such as homotopic contralateral
      motor cortex and ipsilateral thalamic nuclei. These findings indicate that in
      focal epilepsy changes of the genetic programme are restricted to neurons of the
      epileptic focus. In contrast, the increased [14C]deoxyglucose metabolism in
      contralateral motor cortex and ipsilateral thalamus seems to indicate functional
      changes.

PMID- 9191093
TI  - Cloning and characterization of Kir3.1 (GIRK1) C-terminal alternative splice
      variants.
AB  - Southern blot analysis of RT-PCR products from brain and heart revealed multiple
      products for a C-terminal region of Kir3.1. Sequencing yielded clones for wild
      type Kir3.1 and three Kir3.1 C-terminal alternative splice variants, including a
      unique alternative exon. Two of these variants encoded truncated Kir3.1
      molecules. Tissue distribution and electrophysiological characterization of a
      single truncated variant, Kir3.1(00) were then examined. Kir3.1 channels are
      gated by G-protein beta gamma-subunits binding to the C-terminal domain, thus,
      the truncation of Kir3.1(00) removes a major functional domain. When incorporated
      into heteromeric channels with other family members (Kir3.1, 3.2 or 3.4) several
      functional changes were observed: (1) Kir3.1(00) changes G-protein activation of
      Kir3 channels; (2) Kir3.1(00) is restricted in its ability to assemble with other
      channel subunits as heteromers; and (3) incorporation of Kir3.1(00) into
      heteromeric channel complexes alters the kinetics of channel re-activation.

PMID- 9191094
TI  - Tissue-specific methylation occurs in the essential promoter element of the
      tyrosine hydroxylase gene.
AB  - Expression of tyrosine hydroxylase (TH) is regulated in a tissue-specific manner
      by multiple mechanisms. In catecholaminergic cells, the expression of TH-mRNA is
      up-regulated by forskolin (FK) and is suppressed by retinoic acid (RA). We have
      previously provided evidence that, in N-18 cells, the expression of TH-mRNA is
      suppressed by DNA methylation of the TH gene itself. In the present study, using
      a catecholaminergic cell line, N1E-115, we performed deletional and mutational
      analyses on the 5'-flanking region of the mouse TH gene. The results indicate
      that a cAMP response element (CRE) mediates constitutive transcription of the TH
      gene, as well as responsiveness to FK and RA. Using bisulfite sequencing methods,
      we analyzed the methylation status of the TH gene 5'-flanking region in various
      cell lines and rat tissues. We found that three cytosine residues in the domain
      surrounding the CRE of the TH gene promoter were specifically methylated in N-18
      cells and TH non-expressing rat tissues. In contrast, these cytosines were
      undermethylated in TH expressing cell lines and tissues. The inverse correlation
      between the frequency of cytosine methylation at these specific sites and the
      levels of TH expression supports a role for DNA methylation in the regulation of
      tissue-specific gene expression.

PMID- 9191095
TI  - Transcriptional regulation of the human S100 beta gene.
AB  - S100 beta is a calcium-binding protein produced and secreted by glial cells in
      the central and peripheral nervous systems. S100 beta promotes neuronal
      differentiation and survival but may be detrimental to cells if overexpressed.
      The selective overproduction of S100 beta has been implicated in the progression
      of the neuropathological changes in Alzheimer's disease. In addition, at high
      concentrations, S100 beta stimulates toxic intracellular pathways in cultured
      cells. To begin to define the regulation of S100 beta expression, we
      characterized the human S100 beta promoter and mapped its upstream regulatory
      elements by using a luciferase reporter system. The functional S100 beta promoter
      was localized to a region -168/ +697 containing 168 bp upstream of the
      transcription initiation site of the gene. This minimal promoter was active in a
      variety of cell types, including those of glial, neuronal, and non-neural origin.
      The human S100 beta promoter activity is regulated by both positive and negative
      regulatory elements located upstream in the 5' flanking DNA regions. The regions 
      788/ -391 and -1012/ -788 contain strong positive, cell type-specific regulatory
      elements. Negative regulatory elements were mapped to the more distal -4437/ 
      1012 and -1012/ -788 regions of the gene. The -4437/ -1012 negative element
      suppressed promoter activity in all cell types examined, except C6 glioma cells.
      These data demonstrate that the expression of the human S100 beta gene is under
      complex transcriptional regulation that allows for precise control of the S100
      beta level in the nervous system.

PMID- 9191096
TI  - Localization of mRNA for fatty acid transport protein in developing and mature
      brain of rats.
AB  - Gene expression for rat fatty acid transport protein (FATP) and fatty acid
      translocase (FAT) were examined by Northern and in situ hybridization analysis.
      In Northern blot analysis of developing brain, FATP mRNA was detected weakly
      throughout all developing stages without any changes in the expression level,
      while no gene expression for FAT mRNA was detected at any stages. By in situ
      hybridization histochemistry, intense expression was seen in the ventricular
      germinal zone on pre- and perinatal stages, whereas distinct expression was
      observed in the cerebellar Purkinje and granule cell during postpostnatal
      development. No expression was detected in the cerebellar external granule cell
      layer. Because of the high expression of FATP mRNA in the embryonic ventricular
      zone and the postnatal cerebellar cortical neurons in parallel to the gene
      expression for fatty acid binding protein (FABP) which we have recently reported,
      co-operated involvement of FATP and FABP in the active uptake of long-chain fatty
      acids is plausible in these cells.

PMID- 9191097
TI  - Distribution of the neuropeptide Y Y2 receptor mRNA in rat central nervous
      system.
AB  - Our group has recently reported the expression cloning of the human neuropeptide
      Y Y2 receptor DNA and subsequently the cloning of the rat homologue. These
      studies have made it possible to localize the mRNA encoding this NPY receptor
      subtype in rat tissues. We have, thus, carried out in situ hybridization studies,
      using radiolabeled oligonucleotide probes to the rat Y2 receptor mRNA, to
      determine the distribution of Y2 mRNA in rat brain and limited peripheral
      ganglia. Probe specificity was confirmed by testing antisense and sense probes in
      transfected cells. In rat brain, hybridization signals obtained with the
      antisense probes were discrete and were restricted to neuronal profiles in
      specific subregions of the cortex, hippocampus, amygdala, thalamus, hypothalamus,
      mesencephalon and pons. Among the regions exhibiting the most intense labeling
      were the CA3 region of the hippocampus, the arcuate nucleus of the hypothalamus
      and layer 3 of the piriform cortex. Other regions containing labeled neurons
      included the medial amygdala, the centromedial thalamic nucleus, the dorsal
      raphe, the dorsal motor nucleus of the vagus and the trigeminal ganglion. The
      present results indicate that the mRNA encoding the Y2 receptor is discretely
      localized in the rat brain and that the distribution is generally consistent with
      previous radioligand-binding studies. This study should help clarify the
      relationship between the Y2 receptor distribution and functional studies of NPY
      receptor subtype classification and provides further evidence for the involvement
      of the Y2 receptor in multiple physiological processes.

PMID- 9191098
TI  - Induction of Na+/myo-inositol co-transporter mRNA after rat cryogenic injury.
AB  - Myo-inositol is one of the major organic osmolytes in the brain. It is stored in
      the cells by the Na+/myo-inositol co-transporter (SMIT) which is regulated by
      extracellular osmolality. First, in order to confirm that local change of the
      osmolality induces alteration of the SMIT mRNA in brain, we examined change of
      SMIT mRNA of the animals with hypertonic NaCl application to the cortex.
      Application of hypertonic NaCl up-regulated the SMIT mRNA expression widely
      surrounding the application site. We next investigated the role of SMIT in brain
      during vasogenic edema, we examined expression of SMIT mRNA in the rat brain
      after cryogenic injury. The expression of SMIT mRNA was markedly increased 12 h
      after surgery and the induction of the mRNA extended to the entire cortex of the
      affected side. Up-regulated expression was found predominantly in the neurons in
      remote areas. The induction of SMIT mRNA was found until the 3rd day after
      surgery. These findings suggest that osmotic stress may spread over a wide area
      in the cortex in case of vasogenic edema produced by cryogenic injury and that
      the cells respond to this stress by increasing SMIT expression.

PMID- 9191099
TI  - The melanin-concentrating hormone gene in human: flanking region analysis, fine
      chromosome mapping, and tissue-specific expression.
AB  - Genomic sequences encoding the human melanin-concentrating hormone (MCH) were
      isolated from a YAC library and subcloned in pUC vector using a novel E. coli
      transformation method. A 4.1-kb fragment encompassing approximately 1.0 kb of the
      5'-end-flanking region, the three exons-two introns of the coding region and
      approximately 1.7 kb of the 3'-end-flanking region, was sequenced. Comparison
      with the rat MCH gene indicated strong conservation in the 5'-flanking region, in
      particular over the putative TATA box, CAAT box, GRE and AP-1 elements that could
      potentially regulate MCH gene expression. FISH with a fluorescent MCH genomic
      probe on human chromosomes and PCR analysis of a YAC panel mapped MCH to
      chromosome 12q23.1 in a region flanked by D12S1074 and D12S1030 markers.
      Expression of the MCH RNA species and pro-MCH-derived peptides (MCH and NEI) was
      investigated in human tissues by combining Northern blotting, RT-PCR, in situ
      hybridization, immunohistochemistry and RIA. In the human brain, MCH mRNA and
      MCH/NEI peptides were predominantely expressed in the lateral hypothalamus in
      agreement with the known distribution of MCH expression in rat. In addition, MCH
      gene products were detected in extra-hypothalamic sites, such as the pallidum,
      neocortex and cerebellum. In peripheral tissues, MCH mRNA was identified in
      several organs, including the thymus, brown adipose tissue, duodenum and testis.
      An additional shorter MCH gene transcript, likely the result of alternate
      splicing, was revealed in several brain areas and peripheral tissues. While only
      fully processed MCH and NEI were found in hypothalamus, a different peptide form,
      bearing MCH and NEI epitopes, was detected in peripheral organs. This represents
      the first evidence for differential processing of pro-MCH in mammals.

PMID- 9191100
TI  - Differential distribution of mRNAs encoding phosphatidylinositol transfer
      proteins alpha and beta in the central nervous system of the rat.
AB  - The expression of the alpha and beta isoforms of phosphatidylinositol transfer
      protein (PI-TP alpha and PI-TP beta) in the adult rat brain was examined by in
      situ hybridization analysis with isoform-specific RNA probes. PI-TP alpha mRNA
      was detected in rather restricted regions of the brain whereas PI-TP beta mRNA
      was widely distributed in the brain. PI-TP alpha mRNA signals were remarkable in
      neocortex layers II/III and V/VI, Purkinje cell layer, deep cerebellar nuclei of
      the cerebellum, red nucleus and most part of brain stem. Low levels of PI-TP
      alpha transcript were present in CA3 of the hippocampus, ventral and dorsal
      thalamic nuclei, and motoneurons of spinal cord. No hybridization signals was
      obtained in the olfactory bulb, basal ganglia, amygdala, hypothalamus, and
      pituitary gland. In contrast, strong signals of PI-TP beta mRNA were detected in
      the dentate gyrus. The beta isoform mRNA was moderately expressed in olfactory
      bulb, layers II/III of the neocortex, striatum, CA1-CA4 regions of the
      hippocampus, medial habenula, cerebellum, amygdala, hypothalamus, spinal cord,
      and pituitary gland. Thalamus and brain stem contained relatively low, but
      significant levels of PI-TP beta transcript. The distinct distribution of PI-TP
      alpha and PI-TP beta mRNAs suggests different functional roles for each of the
      gene products in the mature nervous system.

PMID- 9191101
TI  - A newly identified membrane protein localized exclusively in intracellular
      organelles of neurons.
AB  - We report here cloning of the cDNA of a novel membrane protein, termed p24,
      which, of the eight mouse tissues tested, was found only in brain where it is
      localized exclusively in neurons. The cDNA encodes 196 amino acids with a
      molecular weight of approximately 24000. P24 contains two putative membrane
      spanning domains and a sequence in the hydrophilic tail homologous to the
      microtubule-binding domain of microtubule-associated proteins, such as TAU and
      MAP-2. We prepared antibodies to p24 and demonstrated that the protein is rich in
      nerve fibers of the cerebral cortex, anterior cerebral nuclei and hypothalamus.
      When neuroblastoma Neuro 2a cells were treated with retinoic acid to induce
      differentiation, p24 mRNA increased but the p24 protein was not detected. The
      protein expressed from the p24 cDNA in non-neuronal Cos-7 cells was 24 kDa in
      size and were localized only in lysosomes. These findings indicate that p24 is a
      neuron-specific membrane protein localized in intracellular organelles of highly
      differentiated neural cells and suggest that it may play a role in the neural
      organelle transport system.

PMID- 9191102
TI  - TrkB expression in dentate granule cells is associated with a late phase of long
      term potentiation.
AB  - Recent studies have demonstrated that the neurotrophins nerve growth factor (NGF)
      and brain-derived neurotrophic factor (BDNF) are induced in hippocampal neurons
      following the induction of long-term potentiation (LTP), a model of memory, and
      that BDNF and NT-3 (but not NGF) can induce LTP-like increases in synaptic
      efficacy. Receptors for these neurotrophins have been cloned and characterized
      and we investigated whether LTP alters the expression of two neurotrophin
      receptors, trkB (BDNF receptor) and trkC (NT-3 receptor) in dentate granule
      neurons of the hippocampus using in situ hybridization analysis. Results show
      that trkB is strongly induced in these neurons in an N-methyl-D-aspartate (NMDA)
      receptor-dependent manner. Moreover, the induction of trkB and trkC mRNAs was
      attenuated by sodium pentobarbital, which interferes with the durability of LTP.
      Low-frequency stimulation of the perforant path had no effect on trkB mRNA levels
      but significantly reduced trkC mRNA in dentate granule cells. Thus, both BDNF and
      its receptor trkB are induced in granule cells by stimulation that produces
      durable LTP, suggesting that this neurotrophin and its receptor play an important
      role in memory formation and may be suitable targets for the development of
      cognitive-enhancing drugs in the treatment of diseases, such as Alzheimer's.

PMID- 9191103
TI  - Distribution of AMPA receptor subunit mRNAs in the human basal ganglia: an in
      situ hybridization study.
AB  - The distribution of AMPA receptor subunit mRNAs (spliced flip and flop variants
      of GluR-A to GluR-D) in the human post-mortem striatum, nucleus accumbens, globus
      pallidus and basal nucleus of Meynert was determined by in situ hybridization
      histochemistry. In the striatum and nucleus accumbens, for each subunit, the mRNA
      for the flop variant was more enriched than that for the corresponding flip
      variant. The GluR-C(flop) mRNA was most abundant, followed by the GluR-A(flop)
      mRNA. Transcripts for flop forms were evenly distributed in these regions,
      whereas those for flip forms showed a dorsoventral increasing gradient of the
      hybridization signals. The signals in these areas were found to originate mainly
      from medium-sized neurons. In the globus pallidus, mRNAs encoding GluR-A(flop)
      and GluR-C(flop) were also abundantly expressed. The basal nucleus of Meynert was
      enriched for mRNAs of flop forms. In conclusion, AMPA receptors in these areas of
      the human basal ganglia appeared to be mainly composed of flop variants,
      especially GluR-A(flop) and GluR-C(flop). However, the finding that flip
      transcripts were more abundant in the nucleus accumbens than in the striatum
      implies differences in functions of AMPA receptors between the two regions.

PMID- 9191104
TI  - Regulation of hippocampal 5-HT1A receptor mRNA and binding in transgenic mice
      with a targeted disruption of the glucocorticoid receptor.
AB  - Corticosterone is known to suppress levels of 5-HTA(1A) receptor mRNA in rat
      hippocampus. We describe hippocampal 5-HT(1A) receptor mRNA regulation in mice
      that have a targeted disruption of the glucocorticoid receptor gene. 5-HT(1A)
      receptor mRNA levels as well as binding of [3H]8-OH-DPAT, were measured in the
      hippocampus of heterozygous and homozygous GR-deficient mice and in wild-type
      control mice. The effect of adrenalectomy in wild-type mice and heterozygous
      knockouts was also studied. We hypothesized that if the glucocorticoid receptor
      is important as a mediator of the suppressive effect of corticosterone, this
      would be revealed by changed (enhanced) expression of 5-HT(1A) receptor mRNA in
      mice with a genetically changed glucocorticoid receptor status. It was found that
      5-HT(1A) receptor mRNA levels and 5-HT(1A) receptor binding were not different in
      GR-deficient mice. The 5-HT(1A) receptor mRNA levels were responsive to
      corticosterone, as adrenalectomy led to increased levels of hippocampal 5-HT(1A)
      receptor mRNA both in wild-type as in heterozygous knockout mice. These increases
      were paralleled by small but statistically significant changes in [3H]8-OH-DPAT
      binding. These results support a suppressive control of B over 5-HT(1A) receptor
      expression in the hippocampus of the mouse, which is predominantly mediated via
      the mineralocorticoid receptor. The data indicates that no interaction between
      the two corticosteroid receptors is required for this effect of corticosterone,
      and that mineralocorticoid receptor-mediated suppression of gene expression can
      take place in the complete absence of glucocorticoid receptor.

PMID- 9191105
TI  - Induction of heat-shock protein (HSP72) in the cingulate and retrosplenial cortex
      by drugs that antagonize the effects of excitatory amino acids.
AB  - To address the issue of the cytotoxicity of glutamate antagonists, we
      administered representative agents to rats and used HSP72 immunocytochemistry as
      a measure of neuronal injury in the brain. The doses studied spanned the reported
      neuroprotective range for each compound. Some, but not all, glutamate antagonists
      induce neuronal injury in the brain. The non-competitive NMDA antagonists (MK801
      and dextrorphan) demonstrate maximum toxicity. Competitive NMDA antagonists (CGS
      19755 and MDL 100,453) may or may not induce neuronal injury depending on the
      particular compound. The polyamine site (SL 82.0715-10) antagonist does not
      result in neuronal injury. Cingulate and retrosplenial cortex neurotoxicity is
      not a ubiquitous feature of neuroprotective agents that block excitotoxcity, but
      is limited to NMDA antagonists and may depend upon the duration and completeness
      of the blockade of the NMDA receptor.

PMID- 9191106
TI  - Visual sensitivities of nur77 (NGFI-B) and zif268 (NGFI-A) induction in the
      suprachiasmatic nucleus are dissociated from c-fos induction and behavioral phase
      shifting responses.
AB  - Mammalian circadian rhythms are regulated by a pacemaker in the suprachiasmatic
      nucleus of the hypothalamus. Recent work from several laboratories has shown that
      light induces the IEGs, c-fos and jun-B, in the rodent suprachiasmatic nucleus.
      In hamsters, there is a strong correlation between circadian entrainment and the
      induction of c-fos and jun-B in the suprachiasmatic nucleus by light. Previous
      work has shown that the IEGs, nur77 and zif268, both of which encode
      transcription factors, are also light-inducible in the rat suprachiasmatic
      nucleus [Rusak, B., McNaughton, L., Robertson, H.A. and Hunt, S.P., Circadian
      variation in photic regulation of IEG mRNAs in rat suprachiasmatic nucleus cells,
      Mol. Brain Res., 14 (1992) 124-130.; Sutin, E.L. and Kilduff, T.S., Circadian and
      light-induced expression of IEG mRNAs in the rat suprachiasmatic nucleus, Mol.
      Brain Res., 15 (1992) 281-290.]. To characterize the photic-regulation of these
      genes in the suprachiasmatic nucleus of golden hamsters, we used in situ
      hybridization to measure nur77 and zif268 mRNA levels with 33P-labeled
      complementary RNA probes. 5-min monochromatic light pulses at CT19 induced a
      dramatic increase in both nur77 and zif268 mRNA levels. Peak mRNA levels occurred
      45-60 min after light onset for both nur77 and zif268. In addition, the induction
      of both nur77 and zif268 mRNA levels was gated by the circadian pacemaker. Light
      pulses during subjective day (CT3 and CT9), which do not cause behavioral phase
      shifts, did not significantly alter mRNA levels of either nur77 or zif268;
      whereas light pulses during the subjective night (CT14 and CT19), which induce
      phase-shifts, dramatically increased both nur77 and zif268 mRNA levels. In
      contrast to c-fos induction, which has a photic threshold indistinguishable from
      that of the behavioral phase-shifting response, nur77 and zif268 mRNA induction
      were found to have visual sensitivities greater than the phase-shifting response
      by 1-2 log units (10-100-fold). Although light and circadian phase regulate nur77
      and zif268 expression in the SCN, these results demonstrate that their induction
      is not rate-limiting for photic entrainment of the hamster circadian system.

PMID- 9191107
TI  - Identification in the rat neurotensin receptor of amino-acid residues critical
      for the binding of neurotensin.
AB  - In order to identify charged amino-acid residues of the cloned rat brain
      neurotensin (NT) receptor (NTR) that are critical for NT binding, we performed
      site-directed mutagenesis on the cDNA encoding this protein, followed by
      transient expression into mammalian COS-7 cells and in Xenopus laevis oocytes.
      Point substitutions of charged residues in the N-terminal part and in the 2nd and
      3rd extracellular loop of the receptor either did not affect (125)I-Tyr3-NT
      binding or resulted in a decrease in binding affinity by a factor of 2-3.
      Mutations of amino acids Asp113 in the second transmembrane domain (TM) and of
      Arg149 or Asp150 in TM III yielded receptors that bound NT as efficiently as the
      native receptor. By contrast, replacement of the Asp139 residue in the 1st
      extracellular loop, or of Arg143 or Arg327-Arg328 residues at the top of TM III
      and in TM VI, respectively, completely abolished ligand binding. Confocal and EM
      immunocytochemical studies of the expression of these affected receptors, tagged
      with the C-terminal sequence of the vesicular stomatitis virus glycoprotein (VSV
      G), indicated that this loss of binding was not due to altered receptor
      expression or to their improper insertion into the plasma membrane. When these
      mutated forms of neurotensin receptor were expressed into Xenopus oocytes, Asp139
      Gly- and Arg143-Gly-modified receptors remained functional in spite of a lowered
      response to NT whereas the Arg327-Arg328 mutant form was totally insensitive to
      NT at concentrations up to 10 microM. In the case of the Arg327-Arg328 mutation,
      the observed insensibility to NT could be the result of a drastic conformational
      alteration of this mutant protein. By contrast, it would appear that Asp139 and
      Arg143 residues located in the first extracellular loop of the receptor may be
      directly involved in the interaction of the receptor with neurotensin.

PMID- 9191108
TI  - Temporal and spatial expression of glutamic acid decarboxylases in human fetal
      brain.
AB  - The expression of two isoforms of glutamic acid decarboxylase, GAD67 and GAD65,
      was analyzed in central nervous system (CNS) tissues obtained from normal second
      trimester human fetuses after elective termination of pregnancy. After RT-PCR
      amplification of sequences contained in total RNA extracts, Southern blotting
      indicated that GAD67 and GAD65 mRNAs can be detected in frontal pole tissue as
      early as the 12th week of gestation (12 GW). GAD67 message is strongly expressed
      during early second trimester and decreases slightly thereafter but remains
      abundant. In contrast, GAD65 message decreases rapidly and becomes undetectable
      by the 19 GW. However, GAD67 and GAD65 are similar in their spatial expression in
      the CNS at 22 GW. GAD67 and GAD65 messages are highly expressed in the cerebellum
      but expressed in low levels, if at all, in the spinal cord during this
      gestational period. These results suggest that GAD67 may have a greater role in
      neuron differentiation than GAD65 during human brain development.

PMID- 9191109
TI  - Opioidergic and dopaminergic gene expression in the caudate-putamen and accumbens
      of the mutant mouse, tottering (tg/tg).
AB  - Expression of preproenkephalin, dynorphin and D2 dopamine receptor mRNAs was
      examined in selected regions of the forebrain of homozygous and heterozygous
      tottering mice, using in situ hybridization histochemistry. Homozygous tottering
      mice carry an autosomal recessive mutation causing them to exhibit petit mal-like
      epilepsy. Preproenkephalin mRNA levels were significantly higher in the lateral
      caudate and the core of the nucleus accumbens of homozygous tottering mice
      compared to wild-type controls. No differences were observed in the expression of
      dynorphin and D2 receptor mRNA distribution in brain regions examined in the
      mutant mice as compared to wild-type controls.

PMID- 9191110
TI  - Anoxia regulates gene expression in the central nervous system of Drosophila
      melanogaster.
AB  - We took advantage of the Drosophila melanogaster's extraordinary resistance to
      anoxia to study the molecular mechanisms underlying this phenomenon. We analyzed
      mRNA expression of heat shock proteins (HSP) (HSP26 and HSP70), ubiquitins (UB)
      (UB3 and UB4), cytochrome oxidase I (COXI) and superoxide dismutase (SOD) using
      slot blot analysis. The expression of HSP genes, especially HSP70, was remarkably
      up-regulated (up to a thousand-fold) while those of UB4 and COXI were down
      regulated (10-60%) in response to the anoxic stress. The expression of UB3 gene
      was up-regulated by 1.5x and the expression of SOD gene was not significantly
      affected. In response to heat shock stress, the expression of HSP genes increased
      by up to several thousand-fold, the expression of UB genes increased modestly (23
      91%) but the expression of SOD and COXI genes was reduced by 25%. Furthermore,
      the expression patterns of HSP genes under anoxia and heat shock were clearly
      different. The expression of HSP genes peaked by 15 min into anoxia and then
      declined but stayed above baseline. In contrast, their expression increased as a
      function of time during heat exposure. From these results, we conclude that: (1)
      different forms of stress regulates gene expression in different ways; (2) anoxia
      differentially regulates gene expression; and (3) the up-regulation of HSP70 and
      down-regulation of UB4 by anoxia are consistent with the idea that Drosophila
      melanogaster resist anoxia, at least in part, by protecting proteins against
      degradation.

PMID- 9191111
TI  - Molecular cloning of a new unc-33-like cDNA from rat brain and its relation to
      paraneoplastic neurological syndromes.
AB  - Anti-CV2-autoantibodies from patients with paraneoplastic neurological syndromes
      were used to purify protein(s) related to this disease. A novel cDNA, c-22, was
      obtained by PCR with primers based on amino-acid sequence of peptides obtained
      from this protein and rat brain cDNA as template. The deduced amino-acid sequence
      of c-22 shows homology to the Unc-33 gene from C. elegans in which mutations lead
      to defects in neuritic outgrowth and axonal guidance and cause uncoordinated
      movements of the nematode. Several consensus sites for putative protein kinase C
      phosphorylation were found, suggesting that the c-22 gene product may be a
      phosphoprotein. Northern hybridizations show that the apparently unique 3.8-kb
      mRNA of c-22 is present in rat brain tissue and its expression is developmentally
      regulated: the levels of C-22 mRNA, detectable in brain at embryonic day 17
      (E17), increase up to post-natal day 7 (P7) and decline rapidly to an almost
      undetectable level in adult.

PMID- 9191112
TI  - Absence of neuroanatomical and behavioral deficits in L7/pcp-2-null mice.
AB  - L7/pcp-2 is expressed exclusively in cerebellar Purkinje and retinal bipolar
      neurons. While the function of L7/pcp-2 is unknown, its mRNA is trafficked into
      dendrites, suggesting a role in dendritic physiology. To elucidate its function,
      L7/pcp-2-null mice were generated. These mice are neurologically normal with no
      signs of cerebellar or retinal dysfunction. The mice are indistinguishable from
      wild-type littermates with regards to gross neuroanatomy and fine structure of
      Purkinje cell dendrites.

PMID- 9191113
TI  - Calcium- and calmodulin-dependent phosphorylation of AMPA type glutamate receptor
      subunits by endogenous protein kinases in the post-synaptic density.
AB  - We have detected immunoreactivities of AMPA receptor subunits GluR1-4 in post
      synaptic density (PSD) fraction and tested whether they can be phosphorylated by
      endogenous kinases. Incubation of PSD with Ca2+ and calmodulin increased
      phosphorylation of GluR1 and GluR2/3. The phosphorylation of GluR1 was largely
      blocked by a Ca2+/calmodulin-dependent protein kinase type II inhibitor. Thus
      Ca2+/calmodulin-dependent phosphorylation of glutamate receptor may be a
      mechanism underlying enhanced post-synaptic receptor responsiveness in LTP.

PMID- 9191114
TI  - Ovariectomy and estradiol treatment affect the dopamine transporter and its gene
      expression in the rat brain.
AB  - The impact of gonadal hormone withdrawal and estrogen therapy was investigated on
      the rat dopamine transporter (DAT). Short-term ovariectomized (ST-OVX, 2 weeks)
      and long-term ovariectomized (LT-OVX, 3 months) rats were treated or not with
      17beta-estradiol (E2) for 2 weeks. DAT mRNA expression was measured by in situ
      hybridization in the substantia nigra pars compacta (SNc) for the nigrostriatal
      pathway and the ventral tegmental area (VTA) for the mesolimbic pathway whereas
      DAT levels were assessed by [3H]GBR-12935 autoradiography, respectively, in the
      striatum and the nucleus accumbens. Ovariectomy produced a time-dependent
      decrease of the DAT density in the striatum and the nucleus accumbens and the E2
      treatment did not significantly restore these DAT levels. Neither ST-OVX nor E2
      treatment of the ST-OVX animals altered the DAT mRNA expression in the SNc and
      the VTA. However, LT-OVX animals showed increased DAT mRNA levels in these
      regions. E2 treatment of LT-OVX animals partially restored DAT mRNA levels in the
      SNc and left these levels unchanged in the VTA. These opposite variations induced
      by OVX on the DAT density and their mRNA levels suggest the involvement of non
      genomic mechanisms, such as post-transcriptional events and/or membrane effects.
      Altered neurotransmission following gonadal hormone withdrawal may contribute to
      CNS disorders occurring at menopause in predisposed women. Ovariectomized rats
      constitute a useful model to study the changes in neurotransmitters balance
      occurring after menopause.

PMID- 9191116
TI  - Histones, nucleosomes and the roles of chromatin structure in transcriptional
      control.

PMID- 9191115
TI  - Regulation of the activity of the transcription factors AP-1 and NFAT during
      differentiation of precursor CD4+ T-cells into effector cells.

PMID- 9191117
TI  - Stat4- and Stat6-deficient mice as models for manipulating T helper cell
      responses.

PMID- 9191118
TI  - TcR zeta/CD3 signal transduction in T-cells: downstream signalling via ZAP-70,
      SLP-76 and FYB.

PMID- 9191119
TI  - Haemopoietic growth factors and leukaemogenesis.

PMID- 9191120
TI  - Interleukin 15.

PMID- 9191121
TI  - Intracellular targeting, interaction with Src homology 3 (SH3) domains and
      rolipram-detected conformational switches in cAMP-specific PDE4A
      phosphodiesterase.

PMID- 9191122
TI  - Regulation of the expression of distinct human secreted IgE proteins produced by
      alternative RNA splicing.
AB  - The use of splice sites for human epsilon mRNAs is tightly regulated, as the
      potential number of splice products far exceeds that actually produced. Our
      studies show that use of the epsilon alternative splices is regulated by a
      limited number of stimuli, and the relative production of the epsilon mRNA
      variants follows a developmental profile. In addition, we have found disease
      related changes in the pattern of epsilon mRNA variants encoding distinctive IgE
      isoforms. Analysis of the biological activity of expressed recombinant IgE
      proteins and measurement of their levels in disease conditions will directly
      answer questions as to the biological relevance of the changes observed in
      epsilon mRNA splicing. This information will then be able to be used for rational
      therapeutic design interventions in IgE-mediated disorders.

PMID- 9191123
TI  - Structure-based design of peptides that inhibit IgE binding to its high-affinity
      receptor Fc epsilon RI.

PMID- 9191124
TI  - The low-affinity receptor for IgE (Fc epsilon RII or CD23) as a therapeutic
      target.

PMID- 9191125
TI  - Use of peptides to selectively modulate CD4+ T-cell responses.

PMID- 9191127
TI  - cAMP and 'death signals' in a myeloid leukaemia cell: from membrane receptors to
      nuclear responses: a review.

PMID- 9191126
TI  - Regulation of apoptosis through CD95 (APO-I/Fas) receptor-ligand interaction.

PMID- 9191128
TI  - Multi-site phosphorylation of p53 by protein kinases inducible by p53 and DNA
      damage.

PMID- 9191129
TI  - Regulation of lymphocyte migration into lymph nodes by high endothelial venules.

PMID- 9191130
TI  - High-endothelial-venule ligands for L-selectin: identification and functions.

PMID- 9191131
TI  - Structure and function of the mucosal T-cell integrin alpha E beta 7.

PMID- 9191132
TI  - Positive and negative signal co-operativity in the immune system: the BCR, Fc
      gamma RIIB, CR2 paradigm.

PMID- 9191133
TI  - Tyrosine phosphatases in T-cell development and signalling.

PMID- 9191134
TI  - Interleukin 4 and interleukin 13: same response, different receptors.

PMID- 9191135
TI  - Mucosal immunoglobulins and their contribution to defence mechanisms: an
      overview.

PMID- 9191136
TI  - Complement in IgA immune-complex-induced neutrophil activation.

PMID- 9191137
TI  - IgA antibody as a non-inflammatory regulator of immunity.

PMID- 9191138
TI  - Recombinant secretory IgA for immune intervention against mucosal pathogens.

PMID- 9191139
TI  - The polymeric immunoglobulin receptor: structure and synthesis.

PMID- 9191140
TI  - New functions of the MHC class I-related Fc receptor, FcRn.
AB  - FcRn was originally identified as the receptor responsible for IgG binding to the
      intestinal epithelium of neonatal rats and mice. FcRn transports IgG from milk
      across the intestinal epithelial cells of the suckling animal. Subsequently, FcRn
      was detected in tissues involved in the transmission of IgG from mother to fetus:
      rat fetal yolk sac, mouse fetal yolk sac and human placental syncytiotrophoblast.
      In addition, FcRn mRNA has been detected in many tissues of adult rats, mice and
      humans, and FcRn is present in several adult tissues and in cell lines. The
      selective protection from catabolism of IgG compared with other immunoglobulins
      is lost in mice that lack functional FcRn. One function of FcRn in tissues that
      do not transport IgG, and beyond the perinatal period, is thus to rescue
      circulating IgG from degradation. These recent observations reveal a more
      widespread use of FcRn than had been supposed.

PMID- 9191141
TI  - Origin and structure of pathogenic IgA in IgA nephropathy.

PMID- 9191142
TI  - Novel components of mammalian stress-activated protein kinase cascades.

PMID- 9191143
TI  - Regulation of transcription factor function by proteolysis.

PMID- 9191144
TI  - Intracellular signalling pathways regulating initiation factor eIF4E
      phosphorylation during the activation of cell growth.

PMID- 9191146
TI  - Signalling and adhesive properties of the integrin leucocyte function-associated
      antigen 1 (LFA-1).

PMID- 9191145
TI  - Role of the double-stranded RNA-activated protein kinase (PKR) in cell
      regulation.

PMID- 9191147
TI  - Peripheral blood fibrocytes: novel fibroblast-like cells that present antigen and
      mediate tissue repair.

PMID- 9191148
TI  - Expression of extracellular matrix molecules, proliferation markers and cyclin
      dependent kinase inhibitors in inflamed tissues.

PMID- 9191149
TI  - T-lymphocyte-fibroblast interactions.
AB  - At the end of the immune response, activated T-cells are cleared by apoptosis. T
      cell apoptosis induced by cytokine deprivation can be inhibited by the addition
      of exogenous cytokines or by a fibroblast-derived survival factor. Under normal
      circumstances, fibroblast-mediated T-cell survival may allow persistence of a
      small number of primed T-cells in tissues, which can be reactivated to initiate a
      secondary immune response. In abnormal situations, fibroblast-mediated T-cell
      survival may lead to the persistence of large numbers of T-cells producing a
      chronic inflammatory state. Evidence derived from wound healing suggests that a
      bidirectional interaction is possible, and T-cells are also capable of regulating
      fibroblast behaviour. Persistent T-cells in the wound site thus prolong a
      scarring response. Potential manipulation of these interactions would provide a
      novel strategy for developing new therapeutic interventions. For example,
      administration of the fibroblast survival factor that inhibits T-cell apoptosis
      may prolong lymphocyte survival in lymphopenic states such as AIDS. Inhibition of
      the survival factor on the other hand not only has potential in the treatment of
      chronic inflammatory states, but may also be of value in regulating scar
      formation with implications for the treatment of many diseases.

PMID- 9191150
TI  - Gene therapy for arthritis: principles and clinical practice.

PMID- 9191151
TI  - Gene therapy for primary immunodeficiency.

PMID- 9191152
TI  - Tumour-reactive cytotoxic T-lymphocytes specific for normal cellular proteins.

PMID- 9191153
TI  - Antigens recognized by T-lymphocytes on human tumours.

PMID- 9191155
TI  - Regulation of the stress response by ceramide.

PMID- 9191154
TI  - Sphingolipids as differential regulators of cellular signalling processes.

PMID- 9191156
TI  - Regulation of Raf-1 kinase by interaction with the lipid second messenger,
      phosphatidic acid.

PMID- 9191157
TI  - Protein kinase D: a novel target for diacylglycerol and phorbol esters.

PMID- 9191158
TI  - Nuclear diacylglycerol, the cell cycle, the enzymes and a red herring (or how we
      came to love phosphatidylcholine).

PMID- 9191159
TI  - Determinants of steroid hormone bioavailability.

PMID- 9191160
TI  - Tissue-specific modulation of glucocorticoid action by the 11 beta-hydroxysteroid
      dehydrogenases.

PMID- 9191161
TI  - Update on the human iodothyronine selenodeiodinases, the enzymes regulating the
      activation and inactivation of thyroid hormone.

PMID- 9191162
TI  - Subnuclear trafficking of steroid receptors.

PMID- 9191163
TI  - Steroid-independent activation of steroid receptors in mammalian and yeast cells
      and in breast cancer.

PMID- 9191164
TI  - Mechanisms of transcriptional activation by retinoic acid receptors.

PMID- 9191166
TI  - Three steps in the regulation of transcription by the thyroid hormone receptor:
      establishment of a repressive chromatin structure, disruption of chromatin and
      transcriptional activation.

PMID- 9191165
TI  - TIF1 alpha: a chromatin-specific mediator for the ligand-dependent activation
      function AF-2 of nuclear receptors?

PMID- 9191167
TI  - T-cells with two T-cell receptors: are they important in autoimmunity?

PMID- 9191168
TI  - Role of CD4+CD8- thymocytes in the prevention of autoimmune diabetes.

PMID- 9191169
TI  - Immune deviation towards Th2 inhibits Th-1-mediated autoimmune diabetes.

PMID- 9191170
TI  - Pathogenesis and treatment of virus-induced autoimmune diabetes: novel insights
      gained from the RIP-LCMV transgenic mouse model.

PMID- 9191171
TI  - Molecular mimicry with MHC-derived peptides: does this underlie MHC association
      with autoimmune disease?

PMID- 9191172
TI  - Molecular mechanisms regulating B-cell negative selection.

PMID- 9191173
TI  - The identification of Bruton's tyrosine kinase and Wiskott-Aldrich syndrome
      protein associated proteins and signalling pathways.

PMID- 9191174
TI  - CD28 co-receptor signal transduction in T-cell activation.

PMID- 9191175
TI  - Fine specificity of myelin basic protein reactive T-cells: implications for T
      cell receptor antagonism.

PMID- 9191177
TI  - Enhancement of HLA class II restricted antigen presentation by mannose-receptor
      mediated uptake.

PMID- 9191176
TI  - Nasal tolerance to dominant and subdominant epitopes of collagen type II and
      protection against collagen-induced arthritis.

PMID- 9191178
TI  - Heterogeneity and immunotherapy of specific T-cells in myasthenia gravis.

PMID- 9191179
TI  - Microglia in health and disease.

PMID- 9191180
TI  - T-lymphocyte activation and regulation in the central nervous system.

PMID- 9191181
TI  - Regulation of inducible nitric oxide synthase expression in human glia:
      implications for inflammatory central nervous system diseases.

PMID- 9191182
TI  - The immune response in the Alzheimer's disease brain.

PMID- 9191183
TI  - Natural killer cell regulation during viral infection.

PMID- 9191184
TI  - Molecular genetics of the natural killer gene complex and innate immunity.

PMID- 9191185
TI  - Development and function of natural killer 1+ T-cells.

PMID- 9191186
TI  - Role of natural killer and NK1+ T-cells in regulating cell-mediated immunity
      during Toxoplasma gondii infection.

PMID- 9191187
TI  - Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody
      (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma.

PMID- 9191188
TI  - Recombinant RFB4 single-chain immunotoxin that is cytotoxic towards CD22-positive
      cells.

PMID- 9191189
TI  - Single-chain Fv antibodies for targeting cancer therapy.

PMID- 9191190
TI  - Targeted gene therapy for cancer: herpes simplex virus thymidine kinase gene
      mediated cell killing leads to anti-tumour immunity that can be augmented by co
      expression of cytokines in the tumour cells.

PMID- 9191191
TI  - Do endothelial cells fit the paradigm of antigen-presenting cells?

PMID- 9191192
TI  - Accessory molecules utilized by endothelial cells for allogeneic stimulation of T
      lymphocytes.

PMID- 9191193
TI  - Non-conventional mechanisms of T-cell co-stimulation by endothelial cells.

PMID- 9191194
TI  - Development of a flow-cytometric assay to identify and quantify lymphocytes that
      bind to endothelial and epithelial cells.

PMID- 9191195
TI  - A novel flow-cytometric assay to assess neutrophil adhesion in whole blood.

PMID- 9191196
TI  - DNA vaccination as cancer immunotherapy.

PMID- 9191197
TI  - The regulation of TCF transcription factors by MAP kinase cascades.

PMID- 9191198
TI  - NF-kappa B involvement in IL-1 beta-induction of GM-CSF and COX-2: inhibition by
      glucocorticoids does not require I-kappa B.

PMID- 9191199
TI  - Cytokine regulation of matrilysin gene expression.

PMID- 9191200
TI  - The role of Sp1 in the diet-induced regulation of the rat fatty acid synthase
      [FAS] gene.

PMID- 9191201
TI  - Regulation of the fatty acid synthase gene by retinoic acid in HepG2 cells is
      mediated by an E-box-containing multihormonal response element and two
      neighbouring upstream sequences.

PMID- 9191202
TI  - Specific cytotoxicity against cells bearing HIV1 gp120 antigen by bacteriophage
      encapsidated ricin A chain: implications for cell specific drug delivery.

PMID- 9191203
TI  - Immunological effects of grain dust.

PMID- 9191204
TI  - Epitope mapping of bovine alpha-lactalbumin using a random phage display peptide
      library.

PMID- 9191205
TI  - Detailed epitope mapping of bovine beta lactoglobulin.

PMID- 9191206
TI  - Existence and dissemination of blood serum immunoglobulins in the tissue of the
      rat nerve ganglia.

PMID- 9191207
TI  - Cyclic AMP potentiates the induction of Thy-1 mRNA expression in murine B cells.

PMID- 9191208
TI  - The influence of interleukin-2 administration on met-enkephalins in patients with
      renal carcinoma.

PMID- 9191209
TI  - The down-regulation of MHC class I antigens in rat oligodendrocytes is mediated
      by negative regulatory elements in the class I promoter.

PMID- 9191210
TI  - Reactive oxygen species in experimental allergic encephalomyelitis.

PMID- 9191211
TI  - N-methyl-D-aspartate receptor-mediated events contribute to neurovascular
      breakdown during experimental allergic encephalomyelitis.

PMID- 9191212
TI  - Anti-myelin antibodies modulate experimental allergic encephalomyelitis in Biozzi
      ABH mice.

PMID- 9191213
TI  - Evidence that an anti-SERCA1 monoclonal antibody recognizes the SERCA2b calcium
      pump in pig brain.

PMID- 9191214
TI  - Expression of adhesion molecules on human foetal cerebral vessels: relationship
      to colonisation by microglial precursors.

PMID- 9191215
TI  - Anti-P53 antibodies in the serum of patients with paraneoplastic disease of the
      nervous system.

PMID- 9191216
TI  - CD1 expression in human peripheral nerve of GBS patients.

PMID- 9191217
TI  - Scrapie in immunodeficient mice.

PMID- 9191218
TI  - NK cell lines of different maturational status can be obtained from mouse foetal
      liver.

PMID- 9191219
TI  - Natural killer cell function is altered by freezing in DMSO.

PMID- 9191220
TI  - Genetic regulation of interferon-gamma production.

PMID- 9191221
TI  - Identification of an intragenic promoter in the human CD45 gene.

PMID- 9191222
TI  - NF kappa B in Crohn's disease.

PMID- 9191223
TI  - Cyclic AMP-mediated control of LDL receptor gene expression in human skin
      fibroblasts.

PMID- 9191224
TI  - Expression of constructs between the glucose-6-phosphatase promoter and a
      reporter gene in an insulinoma cell line: regulation by glucose, dibutyryl cAMP
      and dexamethasone.

PMID- 9191225
TI  - UDP-glucuronyl transferase enzyme family in both human and Balb/c mouse lung.

PMID- 9191226
TI  - Endoplasmic reticulum systems in developing human oesophagus.

PMID- 9191227
TI  - Glucose-6-phosphatase activity: a determinant of brain microsomal intactness.

PMID- 9191228
TI  - Yeast as a tool for the expression of mutant and wildtype glucose-6-phosphatase.

PMID- 9191229
TI  - Induction of the adhesion molecule CD44 by the pro-inflammatory cytokine
      interleukin-1 in endothelial cells.

PMID- 9191230
TI  - Characterisation of the human secretory component gene promoter.

PMID- 9191231
TI  - A NF-AT related protein is implicated in the induction of the immunoglobulin
      kappa 3'-enhancer activity after B cell stimulation.

PMID- 9191232
TI  - The E. coli cAMP receptor protein can be used in a eukaryotic system as a
      repressor activated by cAMP.

PMID- 9191233
TI  - Glucocorticoid inhibition of cytokine-induced E-selectin promoter activation.

PMID- 9191235
TI  - Regulation of initiation factor eIF-2B by GSK-3 regulated phosphorylation.

PMID- 9191234
TI  - Studies on the phosphorylation of eIF4E in Xenopus (XIK-2) kidney cells.

PMID- 9191236
TI  - Signalling pathways which regulate eIF4E.

PMID- 9191237
TI  - Modulation of iron-regulatory protein (IRP) activity in monocytes by nitric
      oxide, phorbol ester and gamma-interferon.

PMID- 9191238
TI  - Heparin modulates endothelial production of monocyte chemotactic peptide-1
      following interferon-gamma stimulation.

PMID- 9191239
TI  - Endothelial cells: heparin modulates the induction of functional antigen
      presentation by IFN-gamma.

PMID- 9191240
TI  - Characterisation and expression of the novel lymphocyte activation antigen using
      the monoclonal antibody 6B2D.

PMID- 9191241
TI  - Monitoring neutrophil phagocytosis in lung cancer patients or normal stem cell
      donors, treated with G-CSF.

PMID- 9191242
TI  - Workers exposed to respiratory hazards show altered expression of cell surface
      markers.

PMID- 9191243
TI  - An assay of neutrophil adhesion to fibronectin and its attenuation by
      pentoxifylline and nitric oxide.

PMID- 9191244
TI  - Generation of a primary immune response to a genetically inactivated (DISC)
      herpes simplex virus and wild type virus.

PMID- 9191245
TI  - Is the success of BCG tumour immunotherapy due to the induction of co-stimulatory
      molecules?

PMID- 9191246
TI  - Clonal T cell responses reflect the expression of multiple DQ genes in cattle.

PMID- 9191247
TI  - Cloning of avian and bovine CD80 using chimeric fusion proteins to detect
      expression.

PMID- 9191248
TI  - Induction of human T cell responses to tumour-associated neoantigens and virus
      antigens using cultured dendritic cells.

PMID- 9191249
TI  - Phagocytic processing of two M protein T-cell epitopes from viable group A
      streptococci.

PMID- 9191250
TI  - Comparison of effects of beta-carotene and lycopene supplementation on the
      expression of functionally associated molecules on human monocytes.

PMID- 9191251
TI  - HLA-DR expression in synovial membrane of juvenile rheumatoid arthritis (JRA)
      versus osteoarthritis (OA).

PMID- 9191252
TI  - The structure and function of the novel MHC class II molecule, HLA-DM.

PMID- 9191253
TI  - The role of neurotrophins in pathological pain states: a novel transgenic rat
      model of hyperalgesia.

PMID- 9191254
TI  - Stimulation of gene expression in neonatal cardiac myocytes by raised
      extracellular pH.

PMID- 9191255
TI  - Protein kinase C isoform expression during differentiation of 3T3-F442A
      preadipocytes.

PMID- 9191256
TI  - Endogenous inhibitors of protein kinase C in pancreatic beta-cells.

PMID- 9191257
TI  - Is type IV phospholipase A2 involved in the regulation of insulin secretion?

PMID- 9191258
TI  - Ganglioside GM1 potentiates the effect of IL-1 beta on neutral sphingomyelinase
      activity in rat brain synaptosomes.

PMID- 9191259
TI  - The human high affinity IgG receptor (Fc gamma RI) signals through the
      immunoreceptor tyrosine-based activation motif (ITAM) of the gamma chain of Fc
      epsilon RI.

PMID- 9191260
TI  - Stimulation of tyrosine phosphorylation and phosphatidylinositol 3-kinase by MCP
      1 in THP-1 cells.

PMID- 9191261
TI  - Differential effects of CB1 and CB2 agonists on cAMP levels and MAP kinase
      activation in human peripheral blood mononuclear cells.

PMID- 9191263
TI  - Dysfunctional focal adhesion kinase (pp125FAK) expression in HIV-infected donor T
      cells.

PMID- 9191262
TI  - Alterations in expression and function of signal transducing proteins in tumor
      associated T and natural killer cells in ovarian carcinoma.

PMID- 9191264
TI  - A recombinant HIV gag p17 protein suppresses the function of normal T cells.

PMID- 9191265
TI  - Cell stresses regulate the phosphorylation state of c-Jun and ATF2 in ventricular
      myocytes.

PMID- 9191266
TI  - Phosphorylation c-Jun and ATF2 in ventricular myocytes by endothelin and
      phenylephrine.

PMID- 9191267
TI  - Activation of gene expression in cardiac myocytes by an antisense to MAP kinase
      phosphatase-1.

PMID- 9191268
TI  - Identification of the transporter for the M-factor mating pheromone in fission
      yeast.

PMID- 9191269
TI  - Characterisation of a phospholipase C delta from Schizosaccharomyces pombe.

PMID- 9191270
TI  - Identification of a putative G protein-coupled receptor kinase in
      Schizosaccharomyces pombe.

PMID- 9191271
TI  - Isolation of yeast mutants hypersensitive to mating pheromones.

PMID- 9191273
TI  - The role of Sxa1 in pheromone recovery in Schizosaccharomyces pombe.

PMID- 9191272
TI  - Sxa2, a carboxypeptidase that degrades extracellular pheromone in fission yeast.

PMID- 9191274
TI  - Pro-sequence removal is not sufficient for activation of the kexin Krp1.

PMID- 9191275
TI  - Induction of tumour necrosis factor-alpha release by hypoxia.

PMID- 9191277
TI  - Tonsil stromal cell lines expressing follicular dendritic cell-like properties-
      isolation, characterization and interaction with B lymphocytes.

PMID- 9191276
TI  - Inflammatory cytokines stimulate human biliary epithelial cells to express
      interleukin-8 and monocyte chemotactic protein-1.

PMID- 9191278
TI  - Metalloproteinases and TIMP-1 in proliferative vitreoretinopathy.

PMID- 9191279
TI  - CCAAT/enhancer binding protein positively regulates the rat 11 beta
      hydroxysteroid dehydrogenase type 1 promoter in liver cells.

PMID- 9191280
TI  - Glucocorticoid receptor mutations in genetically hypertensive rats: markers of
      glucocorticoid insensitivity?

PMID- 9191281
TI  - Multiple copies of the idiotope from the V-88 autoantibody are present in
      germline DNA of both normal and lupus mice.

PMID- 9191282
TI  - Antigen presentation of type II collagen by B cells.

PMID- 9191283
TI  - Generation of autoreactive CD4 T cells in Lewis rats after immunisation and
      culture with bovine type II collage.

PMID- 9191284
TI  - Induction of apoptosis within T lymphoblastoid cells by a topoisomerase I
      inhibitor.

PMID- 9191285
TI  - Activation of phosphatidylinositol 3-kinase following Fas engagement is not
      required for Fas-mediated apoptosis in Jurkat T cells.

PMID- 9191286
TI  - The regulation of apoptosis in resting T lymphocytes.

PMID- 9191287
TI  - Regulation of granulocyte apoptosis by PKC inhibition and elevation of [Ca2+]i.

PMID- 9191289
TI  - Interleukin-10 does not directly affect the constitutive rate of human neutrophil
      or eosinophil apoptosis.

PMID- 9191288
TI  - Transforming growth factor-beta increases the inhibitory effects of GM-CSF and
      dexamethasone on neutrophil apoptosis.

PMID- 9191290
TI  - Effect of the protein phosphatase inhibitors, okadaic acid and calyculin A, on
      dexamethasone-mediated inhibition of neutrophil apoptosis.

PMID- 9191291
TI  - Regulation of human T-lymphocyte proliferative responses by the lipoxygenase
      product 15-HETE.

PMID- 9191292
TI  - beta Galactoside binding protein inhibits B cell growth and induces cell
      apoptosis.

PMID- 9191293
TI  - Glutamine utilization by rat neutrophils.

PMID- 9191294
TI  - Induction of TNF alpha and IL-1 beta mRNA in monocytes by methylglyoxal- and
      advanced glycated endproduct-modified human serum albumin.

PMID- 9191295
TI  - Expression of haematopoietic cell markers by retinal pigment epithelial cells and
      Muller cells.

PMID- 9191297
TI  - Inhibition of neutrophil priming by inhibitors of farnesyl transferase.

PMID- 9191296
TI  - Activated N-RAS causes differentiation of K562 cells.

PMID- 9191298
TI  - Differentiation dependent switch in signalling pathways initiated by Fc gamma RI.

PMID- 9191299
TI  - Interactions with T cells induce expression of VCAM-1 by human intrahepatic
      endothelial cells in vitro.

PMID- 9191300
TI  - Cultured human intrahepatic endothelial cells stimulate alloproliferative
      responses in highly purified CD4 and CD8+ T cells in vitro.

PMID- 9191301
TI  - Vascular adhesion protein-1 and intercellular adhesion molecule-1 mediate T-cell
      binding to human hepatocellular carcinoma.

PMID- 9191302
TI  - Selective migration of highly differentiated primed T cells across human
      umbilical vein endothelial cells.

PMID- 9191303
TI  - Intracellular and cell surface mapping of HLA DR in the presence and absence of
      the invariant chain.

PMID- 9191304
TI  - Purification of L-selectin ligands synthesised by rat peripheral lymph nodes and
      cultured high endothelial cells.

PMID- 9191305
TI  - Adhesion molecules used by T lymphoblasts to interact with cultured high
      endothelial cells.

PMID- 9191306
TI  - Antimalarial activity of nitric oxide: cytostasis and cytotoxicity towards
      Plasmodium falciparum.

PMID- 9191307
TI  - NK cell evolution: studies on Xenopus.

PMID- 9191308
TI  - Interleukin-8 as a growth factor for human colorectal carcinoma cells in vitro.

PMID- 9191309
TI  - IL-1 gene expression in human mammary tumour xenografts after treatment with
      hexadecylphosphocholine.

PMID- 9191310
TI  - HLA class I alterations in head and neck squamous cell carcinoma.

PMID- 9191311
TI  - An assessment of cytokines expressed during antibody-mediated killing of
      colorectal tumour cells using murine and humanised antibodies.

PMID- 9191312
TI  - Isolation of anti-colorectal tumour antibodies from a phage-display library.

PMID- 9191313
TI  - Intracellular colocalisation of the translationally controlled protein P23 with
      cytoskeletal structures.

PMID- 9191314
TI  - Antiproliferative effect of IL-6 on transitional cell carcinoma of the bladder.
      Insight into mechanisms of bacillus Calmette-Guerin immunotherapy.

PMID- 9191315
TI  - Phenotypic and functional analyses of fresh and recombinant interleukin-2
      cultured tumour-infiltrating lymphocytes derived from malignant human liver
      tumours.

PMID- 9191316
TI  - Large scale comparison of adjuvant effects on immunogenicity and protection in a
      herpes simplex virus type 1 vaccination model.

PMID- 9191317
TI  - Cellular and humoral immunity to foot-and-mouth disease virus and its non
      structural proteins in infected swine.

PMID- 9191318
TI  - Immunogenicity & reactogenicity of a recombinant HPV6 fusion protein vaccine
      adjuvanted with monophosphoryl lipid A.

PMID- 9191319
TI  - Cellular immune response to foot-and-mouth disease virus.

PMID- 9191320
TI  - In vivo analysis of immune responses to Cryptococcus neoformans--role of
      interferon-gamma in host resistance.

PMID- 9191322
TI  - Herpes virus-specific immune responses in individuals experiencing recurrent
      genital herpes.

PMID- 9191321
TI  - Theileria annulata "superantigen" activity--TCB usage by responding bovine CD4+
      cells from uninfected donors.

PMID- 9191323
TI  - Early immune events following experimental infection of lambs with Mycobacterium
      avium subspecies paratuberculosis.

PMID- 9191324
TI  - In-situ localisation of immunocompetent cells in Fasciola hepatica infestation in
      rats and mice.

PMID- 9191325
TI  - Immunogenic properties of human papilloma virus type 16 (HPV-16) E5 polypeptide.

PMID- 9191326
TI  - Expression of interleukin-10 mRNA in herpes simplex virus-infected keratinocytes
      in vivo and in vitro.

PMID- 9191327
TI  - Equine dendritic cell infection with equid herpesvirus type 1 reduces their
      ability to support mitogenic T cell proliferation.

PMID- 9191329
TI  - Cytokine profiling of simian immunodeficiency virus infection of cynomologus
      macaques. Pathogenic SIVmac251 pJ5C versus non-pathogenic attenuated SIVmac251
      pC8C reveals divergence.

PMID- 9191328
TI  - Comparison of peripheral blood phenotype in pathogenic and attenuated SIV
      infection.

PMID- 9191330
TI  - C-reactive protein increases C3 deposition on Leishmania donovani promastigotes
      in human serum.

PMID- 9191331
TI  - Interferon-gamma mediates host resistance in a murine model of melioidosis.

PMID- 9191332
TI  - Paracrine enhancement of porcine to murine islet xenograft survival by
      simultaneous fetal pancreas and fetal liver isografts.

PMID- 9191333
TI  - Observations on the biological reactivity of recombinant ovine interleukin-5
      (rovIL-5).

PMID- 9191334
TI  - Interleukin-4 induces myofibroblast differentiation is synovial fibroblasts.

PMID- 9191335
TI  - Modulation of bovine T cell responses by IL-12 and the influence of IL-4 on
      interferon-gamma responses to respiratory syncytial virus.

PMID- 9191336
TI  - The effect of hyperoxia on the expression of cytokine mRNA in endothelial cells.

PMID- 9191337
TI  - Interleukin 4 and ultraviolet light induced immunosuppression.

PMID- 9191338
TI  - The differential effect of various cytokines on Jar cell proliferation.

PMID- 9191339
TI  - Sex differences in interleukin-4 synthesis by BALB/c mice in response to
      staphylococcal enterotoxin B.

PMID- 9191340
TI  - Medroxyprogesterone acetate reduces the production of cytokines and serotonin
      involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of
      cancer patients.

PMID- 9191341
TI  - Enhancement of immunogenicity of recombinant antigens by production of a cytokine
      antigen fusion protein for vaccination.

PMID- 9191342
TI  - Pulmonary production of cytokines in sudden infant death syndrome.

PMID- 9191343
TI  - CD40 signalling in B cell apoptosis and rescue.

PMID- 9191344
TI  - Lipid signalling in lymphocyte activation and cell death.

PMID- 9191345
TI  - Newborn and adult CD4+CD45RA+ T-cells express similar tyrosine phosphorylation
      profiles.

PMID- 9191346
TI  - T-cell antigen receptor signal transduction in CD45-/- thymocytes.

PMID- 9191347
TI  - Altered protein tyrosine phosphorylation in rheumatoid T cells which is mimicked
      by hydrogen peroxide.

PMID- 9191348
TI  - A p38 MAP kinase inhibitor SB203580 inhibits CD28-dependent T cell proliferation
      and IL-2 production.

PMID- 9191349
TI  - Phorbol esters modulate the coupling of the T cell costimulatory molecule CD28 to
      phosphatidylinositol 3-kinase.

PMID- 9191350
TI  - Distinct mechanisms for rescue from apoptosis in Ramos human B cells by
      signalling through CD40 and interleukin-4 receptor: role for inhibition of an
      early response gene, Berg36.

PMID- 9191351
TI  - T lymphocyte activation and the cellular form of the prion protein, PrPc.

PMID- 9191352
TI  - Analysis of heat shock protein 60 epitopes in transgenic mice.

PMID- 9191353
TI  - A self-peptide with poor stimulatory activity induces T cell tolerance in a self
      reactive human T cell clone.

PMID- 9191354
TI  - Framework and CDR structures of anti-DNA antibodies are implicated in antigen
      binding.

PMID- 9191356
TI  - T-cell subsets in autoimmune haemolytic anaemia.

PMID- 9191355
TI  - T cell cytokine responses to cartilage aggrecan in BALB/c mice.

PMID- 9191357
TI  - Serum galactosyltransferase as a marker of disease activity in rheumatoid
      arthritis.

PMID- 9191358
TI  - Individuals from multiplex insulin dependent diabetes mellitus families express
      higher levels of TCRBV2S1 than controls.

PMID- 9191359
TI  - Iron in synovial fluid: removal by lactoferrin, and relationship to iron
      regulatory protein (IRP) activity.

PMID- 9191360
TI  - Active immunization with anti-DNA autoantibody idiopeptide 88H.64-80 is
      nephritogenic in (NZB x NZW)F1 and Balb/c mice.

PMID- 9191361
TI  - Antibodies to lactoferrin--a possible link between cow's milk intolerance and
      autoimmune disease.

PMID- 9191362
TI  - Functionality of inducible major histocompatibility class II expression by
      specialised non-lymphoid cells.

PMID- 9191363
TI  - Complement is involved in the mechanism of IDDM serum induced pancreatic beta
      cell cytotoxicity.

PMID- 9191364
TI  - Anti-cardiolipin antibodies in blood donors.

PMID- 9191366
TI  - The comparison of the neutrophil respiratory burst elicited by human secretory
      IgA or serum IgA.

PMID- 9191365
TI  - A human monoclonal antiendothelial cell autoantibody uses a VH gene associated
      with an anti-DNA autoantibody.

PMID- 9191367
TI  - Mutagenesis of J chain residues critical for IgA dimer assembly.

PMID- 9191368
TI  - Immunoglobulin genes from human duodenal and colonic plasma cells are mutated.

PMID- 9191370
TI  - Smoking and immune responses in pigeon fanciers' lung.

PMID- 9191371
TI  - A single diversified VH gene family dominates the bovine immunoglobulin
      repertoire.

PMID- 9191372
TI  - Multiple transcripts of human IgA Fc receptor CD89 in neutrophils, eosinophils
      and the monocyte-like cell line THP-1.

PMID- 9191373
TI  - Probing the Fc alpha R binding site on IgA by mutagenesis of the IgA Fc region.

PMID- 9191374
TI  - The effect of mutagenesis of the human IgA1 hinge residue Thr228 on cleavage by
      IgA1-specific proteases.

PMID- 9191375
TI  - Development of a human IgA antibody specific for the tumour antigen TAG-72.

PMID- 9191376
TI  - Purification of high Mr forms of IgA1 from human serum: demonstration of binding
      to human B-lymphocytes.

PMID- 9191377
TI  - Differential activation of peripheral blood monocytes using various forms of
      human IgA.

PMID- 9191378
TI  - Human neutrophil Fc alpha R and Fc gamma RIIa but not Fc gamma RIIIb generate
      intracellular calcium signals which trigger the respiratory burst.

PMID- 9191379
TI  - Characterisation of serum and mucosal antibodies against Helicobacter pylori.

PMID- 9191380
TI  - Characterization of gene expression following intranasal immunization with
      nucleic acid.

PMID- 9191381
TI  - Mucosal delivery of nucleic acid elicits both cellular and humoral immunity.

PMID- 9191382
TI  - Potential of particulate carriers for the mucosal delivery of DNA vaccines.

PMID- 9191383
TI  - Cellular and humoral responses to microencapsulated Yersinia pestis subunit
      vaccines following oral delivery.

PMID- 9191384
TI  - Influence of maternal nutrition and stress on gut permeability to immunoglobulin
      in newborn lambs.

PMID- 9191385
TI  - A single oral dose of inactivated rotavirus and ISCOM matrices induces partial
      protection in lambs.

PMID- 9191386
TI  - Mechanisms of immunity to the respiratory pathogen Bordetella pertussis in normal
      and gene knockout mice: clearance of primary infection is not enhanced by
      therapeutic interleukin-12.

PMID- 9191387
TI  - Protective mechanisms by omega-6 lipids in experimental autoimmune
      encephalomyelitis (EAE) are associated with cytokines and eicosanoids.

PMID- 9191388
TI  - Effect of omega-6 lipid-rich borage oil feeding on immune function in healthy
      volunteers.

PMID- 9191389
TI  - Transference of fatty acids from macrophages to lymphocytes in culture.

PMID- 9191390
TI  - Macrophages transfer cholesterol to lymphocytes in culture.

PMID- 9191391
TI  - Membrane phosphatidylcholine composition of human lymphocytes in neonates.

PMID- 9191392
TI  - Cytokine secretion by human T cell clones is differentially regulated by
      eicosanoids.

PMID- 9191393
TI  - Serum amyloid A has little effect on high density lipoprotein (HDL) binding to
      U937 monocytes but may influence HDL mediated cholesterol transfer.

PMID- 9191394
TI  - Lipids derived from the mevalonate pathway in HL-60 cells modulate the
      interactions of beta 2 integrins with their ligands.

PMID- 9191395
TI  - The effect of chronic consumption of monounsaturated fat on immune function in
      middle-aged men.

PMID- 9191396
TI  - Dietary fish oil diminishes the antigen presentation activity of rat dendritic
      cells.

PMID- 9191397
TI  - Studies on the down-regulation of major histocompatibility complex class I gene
      expression in adenovirus-transformed cells.

PMID- 9191398
TI  - The mechanism of down-regulation of major histocompatibility complex (MHC) class
      I antigens in highly oncogenic adenovirus 12-transformed cells.

PMID- 9191399
TI  - Herpesvirus saimiri CD59--baculovirus expression and characterisation of
      complement inhibitory activity.

PMID- 9191400
TI  - Protective immunity, but suppressed immune responses to third party antigens are
      generated in cotton rats during measles virus infection.

PMID- 9191401
TI  - CD44 expression in human breast cancer cell lines is related to oestrogen
      receptor (ER) status and confluency in vitro.

PMID- 9191403
TI  - The state of aggregation of MHC class II molecules at the cell-surface is
      temperature dependent.

PMID- 9191402
TI  - Mutations to the alpha-2 domain of human class II molecules alters the efficiency
      of peptide loading and antigen presentation.

PMID- 9191404
TI  - Evidence for ubiquitin-mediated degradation of the DNA repair enzyme for O6
      methylguanine in non-tumour derived human cell and tissue extracts.

PMID- 9191405
TI  - Single particle imaging of cell-surface HLA-DR tetramers.

PMID- 9191406
TI  - Scanning alanine mutagenesis of the second Ig domain of Fc gamma RI indicates
      critical residues for ligand recognition.

PMID- 9191407
TI  - Comparative analysis of phenylalanine hydroxylase A104D mutant, associated with
      variant phenylketonuria, and wild-type enzyme.

PMID- 9191408
TI  - Are gamma delta T lymphocytes involved in intravesical bacillus Calmette-Guerin
      immunotherapy of bladder cancer?

PMID- 9191409
TI  - Ex vivo generation and function of dendritic cells in multiple myeloma.

PMID- 9191410
TI  - Purification and characterisation of soluble intercellular adhesion molecule-1
      and its effect on cell-mediated cytolysis of bladder tumour cells.

PMID- 9191411
TI  - Regulation of superoxide production in human polymorphonuclear leukocytes (PMNs).

PMID- 9191412
TI  - Investigation of the mechanisms of complement mediated cell death in lymphocytes.

PMID- 9191413
TI  - The use of an in vitro wound healing model, the tri-layered skin equivalent, to
      study the effects of cytokines on the repopulation of the wound defect by
      fibroblasts and keratinocytes.

PMID- 9191414
TI  - Comparison of IgA-alpha 1-antitrypsin levels in rheumatoid and reactive
      arthritis.

PMID- 9191415
TI  - Selective migration of the human helper/inducer T-cell subset (CD4+) in BCG
      induced arthritis.

PMID- 9191417
TI  - Characterisation of anti-IgG monoclonal antibody A57H by epitope mapping.

PMID- 9191416
TI  - Effects of Helicobacter pylori colonisation on the adherent gastric mucus
      barrier.

PMID- 9191418
TI  - The universality of immuno-PCR for ultrasensitive antigen detection.

PMID- 9191419
TI  - An enzyme-linked immunosorbent assay for the detection of antigen-specific rat
      immunoglobulin E with improved sensitivity upon a conventional horseradish
      peroxidase-based ELISA method.

PMID- 9191420
TI  - The establishment of an animal model for the screening of food products with
      potentially allergenic constituents.

PMID- 9191421
TI  - Ultrasound characteristics of five common soft-tissue tumours in the hand and
      forearm.
AB  - PURPOSE: This retrospective investigation reviewed the ultrasound images of 96
      benign soft-tissue tumours of the hand and forearm. The aim of the investigation
      was to determine whether there was any correlation between the ultrasound picture
      and the histopathological diagnosis. MATERIAL AND METHODS: Five common types of
      benign tumour in the hand and forearm were studied: localized villonodular
      synovites, haemangiomas, lipomas, nerve tumours, and glomus tumours. Only tumours
      that had been operated on and sent for histopathological examination were
      investigated. RESULTS AND CONCLUSION: The study found 5 key ultrasound
      characteristics that were important for differentiating the tumours: existence or
      not of vessels, existence or not of a capsule, echogenicity, echo structure, and
      pattern of growth. Taking these traits into consideration should make it easier
      for the examiner to make the right diagnosis with a reasonable degree of
      accuracy.

PMID- 9191422
TI  - A statistical model for ultrasound diagnosis of soft-tissue tumours in the hand
      and forearm.
AB  - PURPOSE: The ultrasound characteristics of 5 common tumours of the hand and
      forearm were used to build a statistical model that could assess the weight of
      each trait or combination of traits in the correct diagnosing of the tumours. The
      model was used for calculating the first and second diagnostic alternatives.
      MATERIAL AND METHODS: The basic data of the model were the ultrasound findings in
      previously presented material on the 5 common benign soft-tissue tumours. The
      material consisted of 96 tumours: 18 villonodular synovites, 26 haemangiomas, 14
      lipomas, 27 nerve tumours, and 11 glomus tumours. To build the statistical model,
      the ultrasound characteristics that were significant at 5% level were calculated.
      With stepwise logistic regression, 3 of these were selected as explaining
      variables. The degree of influence of the explaining variable on the response
      variable was calculated by way of odds quotients. The material was then analysed
      by means of the statistical model. The correct diagnosis was calculated as first
      and second alternatives for each tumour and for the whole material. RESULTS: The
      diagnostic accuracy for the whole material was 51% in the first choice and 77% in
      first plus second choices. CONCLUSION: Ultrasound should be the first imaging
      modality for soft-tissue tumours of the hand. However, MR should also be
      performed when diagnosis continues to be obscure and when malignancy is
      suspected.

PMID- 9191423
TI  - Isolated fracture of the posterolateral tibial lip (Volkmann's triangle).
AB  - PURPOSE: To retrospectively evaluate the underlying pathomechanism of isolated
      fracture of the posterolateral tibial lip (Volkmann's triangle), and to
      demonstrate associated radiographic methods. MATERIAL AND METHODS: Retrospective
      analysis of 2500 ankle lesions showed an isolated fracture of the dorsal tibial
      lip in 25 cases. Distal tibial lesions of growing individuals were not
      considered. All patients were examined by radiography in internal oblique and
      lateral views. RESULTS: Sixteen of 25 patients had had their accident during
      winter; 11 had slipped on ice or snow. All 25 patients showed a closed ankle
      lesion in the correct joint position with no clinical signs of instability.
      Evaluation of the standard images showed isolated fracture of the posterolateral
      tibial lip in 24 patients. The fracture was best recognized in the standard
      lateral view in 22 patients. In 2 patients the lateral stress projection
      demonstrated the fracture (20 degrees internal rotation). In one case the
      fracture was only seen on axial CT images. Twenty-two patients with small wedge
      fragments were treated conservatively; 3 with a displaced and large fragment had
      surgical revision and stabilization. Sixteen cases were examined by conventional
      radiography at follow-up examination and 5 of these showed radiological signs of
      arthrosis. CONCLUSION: Plain conventional radiography is still necessary in the
      primary diagnosis of ankle joint lesions. The isolated fracture of the dorsal
      tibial margin is best seen in the standard lateral view. Indication for CT in
      routine diagnostics is limited to cases showing clinical evidence of ankle injury
      without roentgenological signs of a fracture in the standard images. Differential
      diagnoses include the pilon lesion and the Maison-neuve-type fracture.

PMID- 9191424
TI  - Relevancy of radiographic features in elbow fractures.
AB  - PURPOSE: To correlate radiographic and clinical findings of elbow fractures.
      MATERIAL AND METHODS: A retrospective study was made of 110 consecutive adult
      elbow fractures of various types involving the humerus, the ulna, and the radius.
      RESULTS: Twenty-seven fractures with radiographically conspicuous distortions
      healed. Of these only 15 had clinical sequelae. Five had clinical sequelae
      without showing conspicuous radiographic distortions after healing. CONCLUSION:
      For radiographic evaluation and classification purposes, it would seem to be
      important to note the status of the capitellum, the capitellum-trochlear plane,
      and the combination of a distal humerus and a proximal ulna fracture. The outcome
      of common olecranon fractures and injuries to the radial head would seem to
      depend less on a detailed radiographic description.

PMID- 9191425
TI  - Intramuscular myxoma and fibrous dysplasia of bone--Mazabraud's syndrome. A case
      report.
AB  - We present a case of Mazabraud's syndrome, a rare benign disease, with multiple
      intramuscular myxomas of the thoracic wall associated with fibrous dysplasia of
      bone. CT, MR imaging and ultrasonography (US) of the thorax showed 2 well
      circumscribed homogeneous intramuscular tumors. A US-guided needle biopsy with a
      large-core needle (2.0 mm) and a fine needle (0.8 mm) showed that the tumors were
      intramuscular myxomas with no sign of malignancy. 99mTc bone scintigraphy showed
      a markedly increased uptake in the right lower skull, and multiple smaller foci.
      CT of the skull revealed a right-sided unilateral bone thickening of the orbit
      and the ethmoidal cells, and right-sided exophthalmia. This case history suggests
      that patients with multiple intramuscular myxomas should be preoperatively
      examined for osseous lesions. A postoperative follow-up should also be performed
      to detect other soft-tissue myxomas not as yet clinically detectable, or rare
      osseous complications.

PMID- 9191426
TI  - Frequency of unexpected multifocal metastasis in patients with acute spinal cord
      compression. Evaluation by low-field MR imaging in cancer patients.
AB  - PURPOSE: The aim of the study was to estimate, in an acute care service, the
      frequency of multiple-level lesion involvement in patients with clinically
      suspected spinal cord compression or spinal blockage. MATERIAL AND METHODS: Over
      a period of 17 months, 240 patients with symptoms of acute spinal cord
      compression underwent acute MR examination of the spine in a 0.1 T MR unit. The
      cervical spine was only added to the examination if there was clinical suspicion
      of cord compression above Th1. RESULTS: In 65 (27%) of the 240 patients,
      involvement of at least one level was found. Of these patients, 32 (49%) showed
      involvement of more than one level. This high rate was surprising, since only 14
      (44%) of the 32 multiple lesions had been clinically suspected. There was no
      correlation to age or original type of cancer. CONCLUSION: MR accurately
      demonstrates the anatomy of the spine and spinal cord, showing the level and
      complexity of spinal lesions. Multiple lesions may be underestimated when the
      combination of myelography/radiculography and CT is used.

PMID- 9191427
TI  - Ultrasound-guided 1.2-mm cutting-needle biopsies of head and neck tumours.
AB  - PURPOSE: To establish the role of ultrasound-guided cutting-needle biopsy in the
      diagnostic-work-up of tumours in the head and neck region. MATERIAL AND METHODS:
      Seventy-two patients (74 biopsies) with tumours in the head and neck were
      biopsied by means of a biopsy gun fitted with a 1.2-mm biopsy needle (midsized
      needle biopsy, MNB). Twenty-four biopsies were taken from salivary glands, 29
      from lymph nodes, and 21 from miscellaneous locations. Thirty-three of the
      patients were biopsied by MNB under ultrasound guidance after a blinded fine
      needle aspiration biopsy (FNAB) was considered non-diagnostic or non
      representative. RESULTS: In 91% of the cases, the MNB diagnosis was identical to
      the final diagnosis (surgical or radiological/clinical follow-up: at least 6
      months), 9% were false-negative/ non-representative. In 17/33 patients MNB was
      considered to provide more diagnostic information than FNAB, the methods had
      equal accuracy in 12 patients, and in 4 patients the information already gained
      with FNAB was superior to that provided by MNB. The non-diagnostic sampling rate
      for FNAB was 25% versus 3% for MNB. In 26 patients with malignant lymphoma, MNB
      results were diagnostically correct in all but 2 cases. FNAB was correct in 2 of
      9 cases. There were no biopsy-related complications. CONCLUSION: MNB was found to
      be safe and to possess a high degree of diagnostic accuracy, and could therefore,
      particularly in patients with lymphoma, be considered a diagnostic alternative to
      FNAB.

PMID- 9191428
TI  - Gliomatosis cerebri--an appropriate diagnosis? Case reports.
AB  - PURPOSE: To evaluate the premises for the diagnosis gliomatosis cerebri in
      relation to diffuse astrocytomas. MATERIAL AND METHODS: CT, MR images and
      pathological analyses were used to assess the cases of 4 patients with diffusely
      infiltrating astrocytic tumours that radiologically, clinically and
      pathologically resembled gliomatosis cerebri. RESULTS AND CONCLUSION: Some
      astrocytomas have an immense potential for diffuse infiltration and they would
      seem to be more frequent than recognized hitherto. The definition of gliomatosis
      cerebri as a separate entity is questionable, and a diagnosis of diffusely
      infiltrating astrocytoma is recommended in such cases.

PMID- 9191429
TI  - The shortening fraction of myocardial fibers and its layered distribution, as
      derived from cine-MR imaged left ventriculograms. An approach for evaluating
      globar left ventricular function.
AB  - PURPOSE: To evaluate the mean shortening fraction and its SD through the wall
      calculated from multiple cine-MR views, as an estimate of left ventricular globar
      function. MATERIAL AND METHODS: The average myocardial fiber shortening fraction
      was calculated by means of a simple truncated ellipsoid nested shell model. Left
      ventricular parameters, acquired by cine-MR imaging, from 20 healthy volunteers
      served as input. Fiber angles, ventricular torsion and a gradient increase in
      wall thickening from epicard to endocard were part of the model. RESULTS: The
      average fiber shortening fraction was 0.203 (0.158-0.246) +/- 0.021 diastolic
      lengths. It varied only moderately with variations in fiber angle values and not
      at all when the torsion angles were varied within physiological limits. The
      average shortening fraction correlates well with the systolic increase in chamber
      oblonguity (k = 0.837), with the ejection fraction (k = 0.877), and even better
      with the calculated wall thickening (k = 0.973). The average epicardial
      shortening fraction 0.169 (0.142-0.202) +/- 0.016 increased gradually through the
      wall to the endocardial value 0.250 (0.212-0.290) +/- 0.024. The increase in
      chamber length-width ratio from diastole to systole reduced the SD of the
      shortening fraction through the wall layers to a minimum. CONCLUSION: The fiber
      shortening fraction expresses the layered contraction of the myocardial wall, the
      wall thickening, and also the endocardial wall motion. The ejection fraction
      expresses only the latter. The shortening fraction and its SD through the wall
      may prove a valuable additional tool for estimating ventricular globar function.

PMID- 9191430
TI  - CT of experimental hepatoma using the hepatocyte-specific lipid emulsion FP 736
      03.
AB  - PURPOSE: The aim of the study was to investigate whether moderately to well
      differentiated hepatocellular carcinomas (HCC) possess the same ability to take
      up a new lipid emulsion contrast medium, FP 736-03, as do hepatocytes. MATERIAL
      AND METHODS: A rat model of an experimental HCC was used. CT was performed before
      and after an i.v. bolus injection of 1.0 ml FP 736-03/kg b.w. Attenuation values
      of normal liver parenchyma and tumour tissue were measured over time. RESULTS:
      The contrast medium was taken up by the normal liver parenchyma but not by the
      tumour tissue for which the attenuation remained virtually constant over the
      observation period. CONCLUSION: The study demonstrated that FP 736-03 was not
      taken up by the HCC, thus producing a high lesion-to-liver contrast.

PMID- 9191431
TI  - CT with the hepatocyte-specific contrast medium FP 736-04 in an experimental
      model of liver steatosis.
AB  - PURPOSE: To investigate whether liver uptake of the iodinated hepatocyte-specific
      lipid emulsion FP 736-04 is altered by fatty infiltration of the liver. MATERIAL
      AND METHODS: Fatty infiltration of the liver was induced in female Sprague-Dawley
      rats by an intraperitoneal injection of L-ethionine preceded by 15 h of food
      withdrawal. CT of the liver was performed before and 24 h after the
      administration of L-ethionine and, in addition at the latter time point, after an
      i.v. injection of 1.0 ml/kg b.w. of FP 736-04. A control group was subjected to
      the same CT examination protocol. RESULTS: Intraperitoneal administration of L
      ethionine caused liver steatosis, as established by liver triglyceride analysis,
      leading to a significant decrease in the liver attenuation, from 69.2 +/- 2.4 to
      27.8 +/- 12.0 HU. The uptake of FP 736-04 by the fatty liver was significantly
      reduced, yielding a maximum enhancement of 22.3 +/- 7.9 HU as compared to a value
      of 32.3 +/- 5.0 HU in the control group. CONCLUSION: Enhancement by FP 736-04 was
      reduced in the steatotic liver compared with the normal liver. It remains to be
      established whether this degree of enhancement is sufficient for reliable lesion
      detection.

PMID- 9191432
TI  - Percutaneous microwave coagulation therapy in liver tumors. A 3-year experience.
AB  - PURPOSE: Percutaneous microwave coagulation therapy (PMCT) is an interventional
      alternative for inoperable malignant liver tumors. In this paper, we report the
      results of our 3-year experience of PMCT in order to establish suitable
      indications for this treatment. MATERIAL AND METHODS: We studied a total of 27
      inoperable liver tumors in 24 patients. Histology of the tumors showed 20
      hepatocellular carcinomas (HCCs) (13 well differentiated, 4 moderately
      differentiated, and 3 poorly differentiated) and 7 metastases. These tumors were
      treated by PMCT and were followed for 4-40 months (average 18 months). Under US
      guidance, the tumors were coagulated by microwaves emitted from an electrode. The
      changes of tumor size after PMCT were evaluated by CT. When the tumors
      disappeared or were reduced in size after treatment, PMCT was regarded as
      effective. Complications from PMCT were also evaluated. The patient survival rate
      was obtained by means of the Kaplan-Meier method. RESULTS: In tumors of 30 mm or
      less, treatment response was obtained in 70% of cases, while 55% of tumors larger
      than 30 mm responded. The tumor became smaller or disappeared in 85% of the well
      differentiated HCCs, and in 25% of the moderately differentiated HCCs, but none
      of the poorly differentiated HCCs responded. In metastatic tumors, PMCT was
      effective in 57% of cases. Slight pain (24%), fever (20%) and subcutaneous
      hematoma (8%) were experienced immediately after PMCT. In 2 poorly differentiated
      HCCs, needle tract seeding was observed. No case of liver dysfunction was seen
      after PMCT. The overall survival rate was 83.1% at 1 year and 68.7% at 2 years.
      CONCLUSION: Good therapeutic results were achieved with PMCT in lesions of 30 mm
      or less, and in well differentiated HCCs.

PMID- 9191433
TI  - Rim enhancement in colorectal metastases at CT during infusion hepatic
      arteriography. Does it represent liver parenchyma or live tumor cell zone?
AB  - PURPOSE: To evaluate the morphologic substrate of the rim enhancement of of
      colorectal metastases seen at CT during infusion hepatic arteriography (CTIHA).
      MATERIAL AND METHODS: Eleven sector defects in the enhancing rim of 9 metastases
      at CTIHA were analyzed. The corresponding pathologic specimens were investigated
      for sector defects of liver parenchyma. We investigated whether there was a
      correlation between the central angle of the sector defects of rim enhancement at
      CTIHA and that of sector defects in the zone of liver parenchyma in histologic
      slices. The inner and outer diameters of the enhancing rim were also compared
      with the diameter of the metastases as seen at CT during arterial portography
      (CTAP). RESULTS: There was a significant correlation between the central angle of
      sector defects of rim enhancement at CTIHA and the angle of sector defects in the
      zone of liver parenchyma in histologic slices (p = 0.008, Spearman's test). The
      diameter of the metastases measured at CTAP was larger than the inner diameter
      and smaller than the outer diamter of the enhancing rim in CTIHA, i.e. the
      margins of the nodules as seen in CTAP are located in liver parenchyma and not in
      tumor tissue. CONCLUSION: The morphologic substrate of the rim enhancement of
      colorectal metastases seen at CTIHA is liver parenchyma.

PMID- 9191434
TI  - Visualization of tumor vessels in hepatocellular carcinoma. Power Doppler
      compared with color Doppler and angiography.
AB  - PURPOSE: To assess the visualization of tumor vessels in hepatocellular carcinoma
      (HCC) by power Doppler sonography. MATERIAL AND METHODS: We examined 40 patients
      with 47 HCC lesions by means of power Doppler sonography and compared its
      visualization of tumor vessels with those of color Doppler and angiography.
      RESULTS: In 38 (81%) of the 47 lesions, power Doppler sonography improved the
      visualization of tumor vessels compared with color Doppler sonography; in the
      remaining lesions no significant difference was noted. In lesions located within
      7 cm in depth, there was no significant difference between power Doppler
      sonography and angiography. In 10 (83%) out of 12 small (< or = 2 cm in diameter)
      lesions and in 11 (85%) out of 13 hypovascular lesions, power Doppler sonography
      performed considerably better than angiography. In deeper-seated lesions,
      however, angiography was significantly superior to power Doppler sonography.
      CONCLUSION: Power Doppler sonography is more sensitive in detecting the fine
      tumor vessels in most HCCs than color Doppler sonography. In addition, power
      Doppler sonography can replace angiography in evaluating tumor vascularity in
      HCCs except in lesions that are deep-seated or located near the heart. In these
      lesions, angiography can complement power Doppler sonography in demonstrating
      tumor vessels.

PMID- 9191435
TI  - Agenesis of the right lobe of the liver. Case report.
AB  - Agenesis of the right lobe of the liver is an extremely rare congenital anomaly,
      usually accompanied by additional anomalies such as a retrohepatically or
      suprahepatically located gallbladder. In this report we present a new case of
      agenesis of the right lobe of the liver with the Chiliaditi syndrome and a
      subdiaphragmatic hydatid cyst, diagnosed by CT and CT-cholangiography.

PMID- 9191436
TI  - Yield and complications in percutaneous renal biopsy. A comparison between
      ultrasound-guided gun-biopsy and manual techniques in native and transplant
      kidneys.
AB  - PURPOSE: To compare the yield and complications of ultrasound-guided gun-biopsy
      and manual Tru-Cut techniques in percutaneous renal biopsy. MATERIAL AND METHODS:
      A total of 448 biopsies were reviewed. They comprised 124 manual and 131 gun
      biopsies in native kidneys, and 111 manual and 82 gun-biopsies in transplant
      kidneys. The gun-biopsies were performed under real-time ultrasound (US)
      guidance. The manual technique used US mainly for marking the position of the
      kidney. RESULTS: There was a significantly higher diagnostic yield and fewer
      complications in the gun-biopsy group. A total of 8 major complications were
      found, all in the manual group. CONCLUSION: Provided that the operator is
      experienced in US scanning, a switch from the manual technique to real-time US
      guided gun-biopsy will result in the improvement of diagnostic accuracy together
      with a reduced risk of complications.

PMID- 9191437
TI  - Rectal tumours--MR imaging with endorectal and/or phased-array coils, and
      histopathological staging on giant sections. A comparative study.
AB  - OBJECTIVE: To investigate the accuracy of MR imaging in the preoperative staging
      of patients with clinically resectable rectal tumours. MATERIAL AND METHODS:
      Forty-eight consecutive patients with rectal tumours were examined, 29 with a
      pelvic phased-array coil and 19 with a multi-coil arrangement including a pelvic
      phased-array coil and an endorectal coil. MR images and histopathological
      specimens and sections were reviewed independently and tumours were staged
      according to the TNM classification. RESULTS: A more complete visualisation of
      the various layers of the rectal wall was achieved on the endorectal MR images
      than on the pelvic phased-array images. The sensitivity of MR in correctly
      staging T3 tumours compared with histopathology was 81% with a specificity of
      82%. Penetration of the rectal wall was predicted with a sensitivity of 82% and a
      specificity of 87%. Sensitivity and specificity in predicting lymph node
      metastases was 83% and 74% respectively. CONCLUSION: MR imaging with both pelvic
      phased-array and endorectal coils allowed the preoperative staging of rectal
      tumours with a high degree of accuracy.

PMID- 9191438
TI  - Effect of ultrasound contrast medium in color Doppler and power Doppler
      visualization of blood flow in canine kidneys.
AB  - PURPOSE: To examine the effect of an ultrasound contrast medium (UCM) in the
      visualization of parenchymal blood flow by means of color Doppler and power
      Doppler sonography. MATERIAL AND METHODS: Nonenhanced and UCM-enhanced Doppler
      images of canine kidneys were obtained in a transversal plane during various
      states of flow reduction in the anterior branch of the renal artery. The UCM
      consisted of air-filled shell-stabilized microballoons (half-life approximately 2
      min). The images were evaluated blindly by 4 observers who rated the amount of
      flow signal in the cortex and medulla, and categorized the flow state (normal,
      reduced or no flow) in the anterior part of the kidney. RESULTS: The UCM
      increased the area of Doppler signals in the cortex and outer medulla during
      normal or reduced blood flow. The border between nonperfused and normally
      perfused parenchyma was more distinct with the UCM. The categorization of the
      regional flow state was more correct with the UCM. Improvement with the UCM was
      greatest when the nonenhanced Doppler images had suboptimal intensity, but
      positive effects with the UCM were also seen in recordings with adequate
      precontrast intensity. Color blooming artifacts sometimes occurred on the side of
      the kidney facing away from the transducer. CONCLUSION: The UCM improved the
      color Doppler and power Doppler visualization of the parenchymal blood flow in
      the canine kidney, and allowed a more correct categorization to be made of the
      regional blood flow state.

PMID- 9191439
TI  - Percutaneous nephrostomy with real-time sonographic guidance.
AB  - PURPOSE: Percutaneous nephrostomy (PCN) is an effective method for achieving
      temporary drainage of the obstructed urinary system and is usually performed
      under fluoroscopic guidance alone or more commonly under combined sonographic and
      fluoroscopic guidance. We undertook a retrospective analysis of 273 PCNs
      performed solely under ultrasound (US) guidance with the aim of evaluating the
      technique and the safety and efficacy of the procedure. MATERIAL AND METHODS: A
      total of 273 PCN procedures in 267 patients were performed under real-time US
      guidance using the Seldinger technique. The indications for PCNs comprised benign
      (n = 215) and malignant (n = 46) urinary obstruction, and urinary fistulae (n =
      6). RESULTS: PCN was successful in 269 of the 273 attempts (98.5%). Satisfactory
      catheter placement was achieved in 245 of the 269 procedures (91.1%) under US
      guidance. Fluoroscopic assistance for catheter repositioning was required in 24
      PCNs owing to the unsatisfactory position of the catheter tip. Major
      complications occurred in 15 patients (5.6%). Catheter dislodgement and catheter
      blockage was seen in respectively 12.6% and 3.3% of procedures. CONCLUSION: In
      most patients, PCN can be performed safely using real-time sonographic guidance.

PMID- 9191440
TI  - Adding a visual linear scale probability to the PIOPED probability of pulmonary
      embolism.
AB  - PURPOSE: Reporting a lung scintigraphy diagnosis as a PIOPED categorical
      probability of pulmonary embolism offers the clinician a wide range of
      interpretation. Therefore the purpose of this study was to analyze the impact on
      lung scintigraphy reporting of adding a visual linear scale (VLS) probability
      assessment to the ordinary PIOPED categorical probability. MATERIAL AND METHODS:
      The study material was a re-evaluation of lung scintigrams from a prospective
      study of 170 patients. All patients had been examined by lung scintigraphy and
      pulmonary angiography. The scintigrams were re-evaluated by 3 raters, and the
      probability of pulmonary embolism was estimated by the PIOPED categorization and
      by a VLS probability. The test was repeated after 6 months. RESULTS: There was no
      significant difference (p > 0.05) in the area under the ROC curve between the
      PIOPED categorization and the VLS for any of the 3 raters. Analysis of agreement
      among raters and for repeatability demonstrated low agreement in the mid-range of
      probabilities. CONCLUSION: A VLS probability estimate did not significantly
      improve the overall accuracy of the diagnosis compared to the categorical PIOPED
      probability assessment alone. From the data of our present study we cannot
      recommend the addition of a VLS score to the PIOPED categorization.

PMID- 9191441
TI  - The value of MR imaging in prevention of unsuccessful back surgery. A case
      report.
AB  - MR imaging helped in diagnosing a spinal schwannoma, and intradural space surgery
      was thus avoided.

PMID- 9191442
TI  - Plasma levels of prekallikrein, alpha-2-macroglobulin and C1-esterase inhibitor
      in patients with urticarial reaction to contrast media.
AB  - PURPOSE: The plasma levels of prekallikrein, alpha-2-macroglobulin and C1
      esterase inhibitor (C1 INH) in patients with previous urticarial reaction to
      contrast media (CM) were compared to those of a group of nonreacting age- and sex
      matched controls. This study evaluated the value of these laboratory variables in
      predicting acute and delayed urticarial-type reactions. MATERIAL AND METHODS: The
      study comprised 44 patients (reactors) with acute (n = 29) or delayed (n = 15)
      urticaria after administration of CM, and a group of age- and sex-matched
      controls. RESULTS: In the reactors, the levels of prekallikrein and alpha-2
      macroglobulin were higher (p < 0.0001) and the level of C1 INH lower (p < 0.0001)
      than those of the controls. The level of prekallikrein decreased with increasing
      age (p = 0.02) and women had higher values than men (p = 0.0054). The level of
      alpha-2-macroglobulin was age-dependent (p = 0.006). CONCLUSION: Although high
      plasma prekallikrein activity, high plasma alpha-2-macroglobulin activity, and
      low plasma C1 INH activity are associated with urticaria-type reaction to CM,
      their value in predicting urticarial reaction is limited because prekallikrein is
      age- and sex-dependent, and alpha-2-macroglobulin is age-dependent.

PMID- 9191443
TI  - Thrombolysis for acute stroke: a new era in treatment.

PMID- 9191444
TI  - Is more rapid diagnosis of heart attack worthwhile?

PMID- 9191445
TI  - Judging the guidelines for colorectal cancer screening.

PMID- 9191446
TI  - Rural practice and obstetrics fellowships for family physicians.

PMID- 9191447
TI  - Limitations of 'personal formularies'.

PMID- 9191448
TI  - Counseling adolescents about responsible sexual behavior.

PMID- 9191450
TI  - Ascites and malignant ovarian neoplasms.

PMID- 9191449
TI  - Fracture of the os peroneum: an unusual cause of foot pain.

PMID- 9191451
TI  - Screening for coarctation of the aorta.

PMID- 9191452
TI  - Brain attack: emergency treatment of ischemic stroke.
AB  - Thrombolysis has been demonstrated to be an effective treatment for ischemic
      stroke. The major obstacles to more widespread use of this therapy are lack of
      awareness that the treatment is possible and the short (less than three hours)
      therapeutic window. Indiscriminant use of this therapy can lead to an
      unacceptably high rate of intracerebral hemorrhage. Early recognition of the
      onset of stroke. Immediate transfer to a suitably equipped treatment facility and
      careful screening of a computed tomographic scan of the head for signs of early
      infarction are necessary for the safe administration of intravenous thrombolysis.

PMID- 9191453
TI  - Using serum markers in the early diagnosis of myocardial infarction.
AB  - Because thrombolytic therapy can save lives and salvage left ventricular function
      after acute myocardial infarction, rapid and precise diagnosis is essential.
      Electrocardiographic changes, and the patient's history and physical examination
      may not confirm the diagnosis of myocardial infarction. Serum markers have
      specific advantages and disadvantages in confirming this diagnosis. An
      understanding of the advantages and disadvantages of using serum markers can
      enhance the clinician's ability to efficiently and accurately triage patients to
      appropriate care.

PMID- 9191454
TI  - Evaluation and management of facial fractures.
AB  - Facial fractures may portend intracranial and skullbase injury and may lead to
      rapid compromise of the airway. Primary care physicians may provide emergency
      care for patients who have sustained facial trauma. After immediate resuscitation
      and stabilization, management of facial fractures requires knowledge of the
      anatomy, rapid treatment methods and identification of potential associated
      injuries for each type of facial fracture. Differentiation between the life
      threatening aspects of these injuries and the less urgent, but more apparent,
      facial injuries will lessen the risk of complications such as bleeding,
      meningitis and asphyxia. Knowledge of the anatomy of the facial skeleton and of
      the potential injuries associated with each of the various types of facial
      fractures will facilitate effective management decisions. Consultation should be
      sought when functional features are involved or when the injury threatens to
      produce future cosmetic anomalies.

PMID- 9191455
TI  - Comorbid disease in geriatric patients: dementia and depression.
AB  - As the population ages, Alzheimer's disease and depression are becoming
      increasingly common concerns for primary care physicians. While the comorbidity
      of Alzheimer's disease and depression presents a complex diagnostic and
      management challenge, treatment can improve the patient's quality of life.
      Changes in functional status, complaints of pain and fluctuations in mental
      status may signify the onset of depression in a patient with dementia. Because of
      differences in treatment, it is important to separate depression from other
      disruptions in behavior. Unfortunately, screening tools for depression and
      cognitive function are of limited usefulness in patients with Alzheimer's
      disease. Improvement with antidepressant therapy is often diagnostic. The
      caregiver plays a large role in assisting with the diagnosis and assessing the
      effectiveness of therapy.

PMID- 9191456
TI  - Autoimmune bullous diseases.
AB  - Patients with autoimmune bullous diseases are occasionally encountered in primary
      care practice, usually in middle-aged and older patients. The differential
      diagnosis includes nonimmune causes, such as contact dermatitis, infections and
      bullous reactions to drugs or insect bites. An autoimmune blistering disease may
      be distinguished by the age of the patient when the disease first appears, the
      morphology and distribution of the lesions and the presence or absence of mucosal
      lesions and scarring. Because the clinical presentations of blistering disorders
      are often similar, special immunofluorescence tests are used to confirm the
      specific diagnosis. Since diagnosis and management of an autoimmune bullous
      disease may involve systems other than the skin, coordination by the primary care
      physician is crucial.

PMID- 9191457
TI  - Acute ankle injuries: clinical decision rules for radiographse.
AB  - The need to perform "routine" radiographs after every case of ankle trauma has
      been repeatedly questioned, since less than 15 percent of ankle injuries are
      found to involve a significant fracture. Several authors have proposed guidelines
      to define clinical characteristics that may help physicians identify patients
      with a higher probability of having a fracture on the radiograph. The Ottawa
      ankle rules are the latest guidelines developed for the management of ankle
      injuries. These highly sensitive decision rules may allow a significant reduction
      in the number of ankle radiographic series ordered and may decrease patients'
      waiting times and costs without an increased rate of missed fractures or patient
      dissatisfaction.

PMID- 9191458
TI  - Management of diabetes in pregnancy.
AB  - A team approach to diabetes management optimizes pregnancy outcomes for mother
      and baby. Patients with preexisting diabetes require intensive insulin therapy
      before conception and during pregnancy. Glucose self-monitoring assists in
      achieving near-normal glucose levels during pregnancy, with the goal of
      maintaining fasting glucose levels from 60 to 105 mg per dL (3.3 to 5.8 mmol per
      L) and postprandial levels less than 120 mg per dL (6.7 mmol per L). Universal
      screening at 24 to 28 weeks of gestation identifies women with gestational
      diabetes. Dietary measures are used initially in the management of gestational
      diabetes, with the addition of insulin therapy if glucose levels exceed 105 mg
      per dL (5.8 mmol per L) in a fasting state or 120 mg per dL (6.7 mmol per L) two
      hours postprandial. Self-monitoring of blood glucose levels four or more times a
      day guides insulin and dietary modifications. Women with gestational diabetes
      have a higher risk of developing non-insulin-dependent diabetes later in life
      and, thus, warrant long-term follow-up.

PMID- 9191459
TI  - Management of chronic viral hepatitis.
AB  - Chronic viral hepatitis is a leading cause of death worldwide. Four of the six
      identifiable hepatitis viruses are associated with chronic disease. Until
      recently, the only accepted treatment has been injected interferon alfa. New
      antiviral medications currently hold promise in the treatment of hepatitis B.
      Hepatitis C remains more difficult to treat than hepatitis B, but involving the
      patient in selecting the treatment and identifying patients with better responses
      to interferon may help the physician direct the management of such patients more
      successfully.

PMID- 9191461
TI  - Significant FDA approvals in 1996.

PMID- 9191460
TI  - Treatment strategies for Helicobacter pylori infection.
AB  - Peptic ulcer disease is strongly associated with infection by Helicobacter
      pylori, a spiral-shaped, flagellated organism found predominantly in the gastric
      antrum. More than 90 percent of duodenal ulcers and adenocarcinomas of the distal
      stomach are associated with H. pylori infection. Eradication of the organism
      effectively prevents relapses of gastroduodenal ulcers associated with H. pylori.
      In patients undergoing endoscopy, the rapid urease test is highly sensitive and
      specific in diagnosing H. pylori infection. Noninvasive diagnostic methods
      include serologic antibody measurements and urea breath testing. Empiric therapy
      may be tried if the diagnosis is suspected on a clinical basis. Traditional 14
      day "triple therapy" with bismuth, metronidazole and either amoxicillin or
      tetracycline has consistently produced eradication rates of approximately 90
      percent. Newer combination regimens have shown promise in a smaller number of
      studies. No single agent given as monotherapy has proved to be acceptably
      effective in clinical studies.

PMID- 9191462
TI  - AAP establishes treatment recommendations for invasive pneumococcal infections.

PMID- 9191463
TI  - Of mites and men: trypsin-like proteases in the lungs.
AB  - It is no surprise to anyone who has tried to memorize clotting and complement
      cascades that there are a great many trypsin-like proteases-too many, it may
      seem. This fecund enzyme family encompasses such a range of biological roles that
      other important members and functions are sure to await discovery. Of known
      trypsin-like proteases, few, if any, are lung-specific. Nonetheless, many
      contribute in ways critical to lung function, such as fighting microbial
      invaders, regulating the formation and removal of polymerized fibrin, and
      rejecting tumors or transplanted tissues. Some of these enzymes, such as
      plasminogen activators and mast cell tryptases, are native to the lung and live
      where they work; identical enzymes live and work in other tissues. Other enzymes,
      such as most complement and hemostatic proteases, are migrants, typically born
      elsewhere (e.g., the liver). They pass through the lung, looking for something to
      do; if nothing is found, they pass on, circulating, perhaps to return later.
      Still others are unwanted, uninvited intruders, such as dust mite proteases. This
      minireview provides a selective glimpse of the lives of some of the trypsin-like
      enzymes at work in the lung and airways.

PMID- 9191464
TI  - Expression and activity of nitric oxide synthases in human airway epithelium.
AB  - Nitric oxide (NO) synthesized by airway epithelium may be important in the
      regulation of airway inflammation and reactivity. As such, the expression and
      localization of nitric oxide synthase (NOS) isoforms was assessed in human airway
      tissue obtained following thoracotomy, and in cultured human airway epithelial
      (BEAS-2B) cells. NOS expression was determined by reverse transcription
      polymerase chain reaction (RT-PCR)/Southern blot analysis, and localized by in
      situ hybridization and immunohistochemistry. No synthesis by cell cultures was
      detected by nitrite assay. Endothelial and neuronal constitutive NOS mRNAs were
      not detected in airways or cell cultures. Inducible NOS (iNOS) mRNA was detected
      in 5 of 6 airway specimens, and in situ hybridization demonstrated iNOS mRNA
      expression in columnar epithelial cells. This was confirmed by
      immunohistochemistry using an iNOS specific antibody. BEAS-2B cell cultures were
      stimulated with (I) combinations of tumor necrosis factor alpha (TNF alpha) (50
      2,000 U/ml)/interferon gamma (IFN gamma) (20-500 U/ml)/lipopolysaccharide (LPS)
      (10 micrograms/ml) or (2) histamine (10(-3) M-10(-5) M). Cell cultures treated
      with TNF alpha/IFN gamma/LPS in combination expressed iNOS mRNA, and this was
      associated with increases in supernatant nitrite concentrations over 24 h;
      however, this response diminished with successive passage of cells. Histamine
      treatment did not result in iNOS mRNA expression or detectable NO synthesis. We
      conclude that iNOS in human airway tissue is localized to the airway epithelium.
      Cytokine/ LPS stimulation, but not histamine, results in iNOS mRNA expression and
      NO synthesis in BEAS-2B cells. BEAS-2B cells may not be a suitable model for the
      study of NO biology in airway epithelium.

PMID- 9191465
TI  - In vivo gene delivery to the pulmonary circulation in rats: transgene
      distribution and vascular inflammatory response.
AB  - Although gene delivery to the pulmonary circulation has both experimental and
      therapeutic potential, the delivery methods, distribution of transgene, and
      subsequent inflammatory response have been poorly characterized to date. To
      address these issues, we utilized a 0.76-mm OD (outside diameter) end hole
      catheter inserted into the internal jugular vein of adult Sprague-Dawley rats,
      directing the tip into a pulmonary capillary wedge position. We then compared
      infusion of polycationic lipid:DNA complexes to replication-defective adenovirus
      with respect to magnitude and distribution of transgene expression using either
      chloramphenicol acetyltransferase (CAT) or human placental alkaline phosphatase
      (hpAP) reporter genes. Both lipid:DNA and adenovirus resulted in detectable
      transgene expression, though maximum lung CAT activity using lipid (gamma AP
      DLRIE/DOPE) was approximately 2% of maximum activity using adenovirus (Ad-CAT).
      Further characterization of expression after transfection with 10(8) pfu (plaque
      forming units) of Ad-CAT demonstrated persistence of transgene for at least 14
      days (lung CAT activity 27% of maximum). Alkaline phosphatase staining
      demonstrated that both large and small pulmonary arteries as well as the alveolar
      wall expressed transgene. Although little inflammatory response was detected in
      conduit arteries, a predominantly mononuclear cell infiltrate surrounded small
      pulmonary arteries as well as the alveolar spaces in transfected areas of lung.
      We conclude that percutaneous catheter-mediated gene delivery to the pulmonary
      circulation in rats using non-viral and viral vectors is feasible. Although an
      inflammatory response to first generation replication-defective adenovirus was
      detected, it appeared to be largely restricted to the distal pulmonary
      circulation and airspace. This technique should prove useful for investigations
      requiring overexpression of novel genes in the pulmonary artery wall, and could
      ultimately be used to develop gene-based therapies for pulmonary vascular
      diseases.

PMID- 9191466
TI  - Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage
      supernatants and to lavage fluids from crocidolite-exposed rats.
AB  - An early phase of proliferation by mesothelial cells and fibroblasts occurs in
      the lung after asbestos deposition, but the source and identity of the
      cytokine(s) involved is not clear. In the present study, rats received
      crocidolite asbestos intratracheally and were killed at 1 and 6 wk later, animals
      received tritiated thymidine 1 h before death. An increase in inflammatory cells
      was found in bronchoalveolar and pleural lavage fluids at both times, and after 6
      wk the lungs showed fibrosis which was confirmed biochemically. Asbestos fibers
      were found in alveolar and interstitial macrophages but not in pleural
      macrophages. In autoradiographs, both mesothelial cells and fibroblasts showed
      increased DNA synthesis at 1 wk, but only fibroblast labeling was increased at 6
      wk. Lavaged macrophages from the lung (alveolar macrophages; AM) and the pleura
      (pleural macrophages; PLM) were cultured and supernatants tested on rat lung
      mesothelial cells and fibroblasts in vitro; concentrated lavaged fluids were also
      tested. At 1 wk, macrophages secreted growth factors for both cell types but the
      effect was more pronounced using lavage fluids, particularly from the pleura. The
      increase in fibroblast growth was reduced by an antibody to platelet-derived
      growth factor, but this had no effect on mesothelial cells. The growth
      stimulation of these cells was blocked by an antibody to keratinocyte growth
      factor (KGF). Using cell supernatants and lavage fluids from rats 6 wk after
      asbestos, growth stimulation was only observed in fibroblasts. The results
      suggest at least 2 cytokine effects in the lung and pleural space after asbestos
      exposure; one responsible for fibroblast stimulation is seen up to 6 wk later,
      while the other, probably involving KGF, stimulates mesothelial cell
      proliferation in the early response phase after a single exposure to crocidolite.

PMID- 9191467
TI  - CFTR gene transfer reduces the binding of Pseudomonas aeruginosa to cystic
      fibrosis respiratory epithelium.
AB  - Much of the morbidity and mortality seen in cystic fibrosis (CF) is related to
      chronic infection of the respiratory tract with Pseudomonas aeruginosa. Some
      studies have attributed the strong relationship between CF and Pseudomonas
      colonization to the presence of increased numbers of specific cell-surface
      receptors, although other work suggests that this relates to the presence of
      mucus. Several groups are now assessing the use of gene transfer as a novel form
      of treatment for CF. We have examined whether P. aeruginosa binding to freshly
      obtained CF respiratory epithelial cells is increased, and have studied the
      effects of transfer of the CF transmembrane conductance regulator (CFTR) gene on
      this attachment. Binding of P. aeruginosa to noncultured nasal epithelial cells
      from both CF patients (n = 31) and healthy controls (n = 15) was studied with
      scanning electron microscopy. Binding was also assessed for CF cells following
      transfection with CFTR/liposome complexes. Epifluorescence microscopy was used to
      assess the effects of gene transfer on chloride fluxes. Adherence of P.
      aeruginosa directly to the cell surface of CF airway epithelium was significantly
      (P < 0.001) increased over that in non-CF controls. Liposome-mediated CFTR gene
      transfer resulted in a significant (P < 0.01) reduction in the numbers of
      bacteria bound to ciliated epithelial cells. Fluorescence microscopy confirmed
      correction of the basic chloride defect. Thus, in CF, the absence of normal CFTR
      results in increased binding of P. aeruginosa to respiratory epithelial cells.
      This abnormality can be corrected in vitro by restoration of CFTR function. This
      has important implications both for the pathogenesis of CF and for the future
      application and assessment of gene therapy for this disease.

PMID- 9191468
TI  - Myofibroblast involvement in the allergen-induced late response in mild atopic
      asthma.
AB  - We undertook a detailed cellular and ultrastructural examination of bronchial
      biopsies from seven allergic asthmatic patients and 10 nonasthmatic control
      subjects (five atopic and five nonatopic) to determine the nature of the
      inflammation that occurs during allergen-induced late-phase responses (LPRs). The
      asthmatic subjects had mild asthma (FEV1 = 94 +/- 9% predicted; mean +/- SEM) and
      required only intermittent use of beta 2-agonists. Airway mucosal biopsy
      specimens were obtained on a single occasion from the nonasthmatic controls and
      on two occasions from the asthmatic subjects, at 24 h after diluent challenge and
      24 h after challenge with allergen 3 wk later. The mean maximal decrease in FEV1
      during the late response after allergen challenge was 30%, and that after
      administration of diluent was 4%. In coded plastic sections, subepithelial cells
      were counted with both light and electron microscopy, and the numbers present
      were expressed per 0.1 mm2 of tissue. Light microscopy revealed statistically
      significant increases in the total number of inflammatory cells (P < 0.02) and in
      "activated fibroblasts" after allergen challenge (P < 0.05). Electron microscopy
      showed significant increases after allergen challenge in the total number of
      eosinophils (P < 0.05) and cells with the ultrastructural features of
      myofibroblasts. The latter cells constituted 1.5% of cells after administration
      of diluent, and this increased to 15.5% after allergen challenge (P < 0.05). Mast
      cells were significantly more abundant in the atopic nonasthmatic controls than
      in the asthmatic subjects after allergen challenge. The study demonstrates that
      the profile of inflammatory cells in asthma at 24 h after allergen challenge is
      distinct from that in stable asthma and in nonasthmatic controls, and that
      migratory cells with a contractile phenotype appear in greater numbers in the
      late response. We propose that subjects who repeatedly develop a late response
      have increased numbers of migrating, contractile cells that may contribute to
      formation of the increased bronchial smooth-muscle mass observed in fatal asthma.

PMID- 9191469
TI  - Allergen-specific IgE and IL-5 are essential for the development of airway
      hyperresponsiveness.
AB  - The mechanisms underlying the development of airway hyperresponsiveness are not
      fully delineated. We addressed this question by studying the effects of passive
      sensitization with anti-OVA IgE on the development of altered airway
      responsiveness (AR) following local challenge with OVA in normal and athymic
      mice. Both normal and athymic BALB/c mice developed allergen-specific immediate
      cutaneous hypersensitivity after passive sensitization with anti-OVA IgE. In
      contrast, the combination of local challenge with allergen via the airways and
      passive sensitization triggered the development of airway hyperresponsiveness
      only in normal but not in athymic mice. Treatment of athymic mice with IL-5
      significantly increased eosinophil accumulation in the lungs after local
      challenge with OVA; increased airway reactivity was only observed in athymic mice
      which received anti-OVA IgE, not an unrelated IgE, plus IL-5 treatment and airway
      challenge with OVA. These findings identify the requirement for allergen-specific
      IgE and IL-5 for the development of airway hyperresponsiveness following allergen
      challenge via the airways.

PMID- 9191470
TI  - Induction of urokinase-type plasminogen activator receptor by IL-1 beta.
AB  - Extensive tissue remodeling occurs in survivors of acute lung injury, leading to
      nearly normal histology and physiology in the majority of individuals, whereas
      others suffer significant impairment due to the development of pulmonary
      fibrosis. Alveolar epithelial cells play a central role in the repair process.
      They are strategically located to directly participate in the solubilization of
      intraalveolar fibrin deposits, and have the capacity to promote fibrinolysis. We
      have previously reported that interleukin-1 beta (IL-1 beta), an important
      inflammatory mediator in acute lung injury, upregulates urokinase-type
      plasminogen activator expression by human A549 cells (1). In this work, we show
      that IL-1 beta increases cell-surface plasmin generation, mediated in part by
      increased expression of urokinase receptor (u-PAR). Northern blot analyses
      demonstrated that IL-1 beta rapidly induces accumulation of u-PAR messenger RNA
      (mRNA) in a dose-dependent fashion, and that this effect is blocked by
      actinomycin. The IL-1 beta-mediated increase in u-PAR mRNA is inhibited by: (1)
      the relatively specific protein kinase C (PKC) inhibitors 1-(5-isoquinoline
      sulfonyl)-2-methylpiperazine (H7) and calphostin C; and (2) prolonged
      pretreatment of cells with phorbol myristate acetate (PMA), suggesting that PKC
      is an important component of the signaling pathway. Okadaic acid, an inhibitor of
      serine/threonine phosphatases, markedly potentiates the effect of IL-1 beta on u
      PAR mRNA levels. In contrast, dexamethasone, in concentrations as low as 10(-8)
      M, completely blocks the IL-1 beta-mediated increase in u-PAR mRNA. Half-life
      experiments show that dexamethasone has no effect on u-PAR mRNA stability.
      Aldosterone, at concentrations in which it binds primarily to the
      mineralocorticoid receptor, has no effect on u-PAR expression, suggesting that
      the glucocorticoid effect is due to a transrepressive mechanism. In summary, IL-1
      beta increases cell-surface plasmin generation in A549 cells by coordinately
      upregulating urokinase and u-PAR expression. Transcriptional activation of the u
      PAR gene involves PKC-dependent mechanisms, and glucocorticoid suppression is
      probably due to interactions between the glucocorticoid receptor and another
      transcriptional activating system such as activator protein-1 (AP-1) and/or
      nuclear factor-kB (NF-kB).

PMID- 9191471
TI  - Identification of cytokine and adhesion molecule mRNA in murine lung tissue and
      isolated T cells and eosinophils by semi-quantitative reverse transcriptase
      polymerase chain reaction.
AB  - We have used a semi-quantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) assay to detect the expression of mRNA for inflammatory cytokines,
      integrins and selectins in murine lung tissue, and T cells and eosinophils
      isolated from lung and bronchoalveolar lavage (BAL) fluid in an in vivo model of
      ovalbumin (OA)-induced airway inflammation. RNA was isolated from whole lung
      tissue at 1, 6, 24, 48, 72 h, and 7 days after OA inhalation. mRNA for the Th2
      cytokines, IL-4, -5, -6, -10 and -13 in OA-sensitized mice were significantly
      elevated compared with non-sensitized mice. IL-2, TNF-beta, and eotaxin mRNA were
      also increased, but IFN-gamma mRNA was not. P- and E-selectin mRNA levels were
      also enhanced in lung tissue between 6 and 72 h after challenge. Lung T cells
      were isolated by cell sorting with a flow cytometer at 3, 12, 24, 48 and 72 h
      after challenge. mRNA levels for IL-5 and -10 were greater in T cells from OA
      sensitized and -challenged mice than controls at 24 h. BAL fluid from OA
      sensitized and -challenged mice also had significantly higher IL-5 levels than
      controls. BAL fluid T cells and eosinophils were obtained at 48 and 72 h after
      aerosol challenge and were purified by cell sorting. Messenger RNA for IL-1
      alpha, -2, -4, -5, -10, IFN-gamma, and beta 1 were detected in T cells at both
      time points. Transcripts for IL-1 alpha, -4, -5, -13, TNF-alpha and beta, and
      alpha 4, beta 1 and beta 7 were also identified in BAL eosinophils. These data
      show that in addition to murine lung T cells, airway eosinophils may also
      contribute to the inflammatory response by their ability to express mRNA for
      cytokines and integrins.

PMID- 9191472
TI  - Effect of IL-1 beta on responses of cultured human airway smooth muscle cells to
      bronchodilator agonists.
AB  - Decreased beta-adrenergic responsiveness is a characteristic feature of asthma.
      In order to determine whether cytokines released in the asthmatic airway
      contribute to this phenomenon, we measured changes in stiffness of cultured human
      airway smooth muscle (HASM) cells induced by isoproterenol (ISO) in control HASM
      cells and HASM cells pretreated with IL-1 beta (20 ng/ml for approximately 42 h).
      Stiffness was measured by magnetic twisting cytometry. HASM cells were obtained
      from normal tracheal tissue obtained at lung transplant, and studied in passages
      4-7. In control cells, ISO caused a dose-related decrease in cell stiffness. IL-1
      beta had no effect on baseline cell stiffness. However, IL-1 beta caused a
      rightward shift in the concentration-response curve to ISO and decreased the
      maximal effectiveness of this agonist. Decreased responses to ISO were also
      obtained with 2 ng/ml IL-1 beta, or when cells were pretreated with IL-1 beta (20
      ng/ml) for 22 h. This effect of IL-1 beta was not altered by pretreatment of the
      cells with pertussis toxin (100 ng/ml throughout the IL-1 beta exposure period).
      IL-1 beta also significantly attenuated the ability of prostaglandin E2 (PGE2) to
      decrease cell stiffness. In contrast, IL-1 beta had no effect on cell stiffness
      responses to dibutryl cAMP, a cell permeant analog of cAMP suggesting that the
      cytokine does not influence either the ability of cAMP to activate kinases, or
      the targets of these kinases which ultimately mediate cell relaxation. IL-1 beta
      (20 ng/ml for 40 h) caused a small (30%) but significant (P < 0.02) increase in
      basal cAMP, but also resulted in a 2-3-fold decrease in the changes in cAMP
      formation induced by either ISO or PGE2. In contrast, IL-1 beta had no effect on
      cAMP formation in response to forskolin, suggesting that IL-1 beta does not
      mediate its effects via changes in the expression or activity of adenylyl
      cyclase. Pretreatment with IL-1 beta had no significant effect on beta 2
      adrenoceptor number assessed by [125I]-CYP binding in these cells, nor was there
      any significant effect of IL-1 beta on Gsa expression assessed by Western blot.
      In summary, our results indicate that IL-1 beta causes a concentration- and time
      dependent decrease in responses of HASM cells to ISO and are consistent with the
      hypothesis that the effects of IL-1 beta are mediated by uncoupling of beta
      receptors from Gs-induced activation of adenylyl cyclase.

PMID- 9191473
TI  - Tumor progression and cellular differentiation of pulmonary adenocarcinomas in
      SV40 large T antigen transgenic mice.
AB  - Transgenic mice harboring the SV40 early region genes under transcriptional
      control of regulatory regions from the human surfactant protein C (SP-C) gene
      were used to study the progression of pulmonary adenocarcinomas in vivo. SP
      C/SV40 early region gene (SP-C/TAg) transgenic mice consistently developed
      pulmonary adenocarcinomas. Distinct neoplasia was first detected at 4 wk of age
      and large tumor nodules were observed by 20-29 wk of age. SV40 large T mRNA was
      detected in distal bronchiolar and alveolar epithelial cells prior to tumor
      formation and in neoplastic cells at all stages of tumor development. SV40 large
      T mRNA correlated with cyclin-dependent kinase 1 (cdk1) mRNA expression, a marker
      of cellular proliferation. The nonciliated bronchiolar cell marker, CC10 mRNA,
      was detected in the majority of lung tumors at all ages, but was consistently
      decreased in the larger tumor nodules at later stages of tumor progression. CC10
      mRNA was not detected in multiple murine lung epithelial (MLE) cell lines derived
      from the SP-C/TAg mice when cultured in vitro; but was induced in the MLE-15
      clonal cell line when propagated in vivo in the flanks of nude mice. SP-C mRNA,
      an alveolar Type II cell marker, was also expressed in the MLE-15 cells when
      grown in nude mice. However, CC10 and SP-C mRNAs were expressed in distinct,
      nonoverlapping regions of the MLE-15 tumors. These studies support the concept
      that tumor progression is associated with changes in respiratory epithelial cell
      differentiation, and that the expression of bronchiolar and alveolar cell
      specific markers can be induced in a clonal cell line with changes in cellular
      environment.

PMID- 9191474
TI  - Regulation of the secretory phenotype of human airway epithelium by retinoic
      acid, triiodothyronine, and extracellular matrix.
AB  - The purpose of our studies was to identify factors which regulate the composition
      of airway secretions produced by normal human tracheobronchial epithelial (NHTBE)
      cells. Individual factors were removed from the culture media of NHTBE cells
      grown in air-liquid interface (ALI) cultures (which support mucociliary
      differentiation) and the effects on mucin, lysozyme (LZ), and secretory leukocyte
      protease inhibitor (SLPI) secretion and gene expression were examined. Deletion
      of hydrocortisone, epinephrine, transferrin, or gentamycin-amphotericin from the
      media had no reproducible effects; deletion of insulin was incompatible with
      culture growth. We identified 3 factors, namely retinoic acid (RA),
      triiodothyronine (T3) and collagen gel substratum, which had a major impact on
      the profile of NHTBE secretions. Removal of RA from the media caused a drastic
      decrease in mucin secretion and a decrease in expression of the mucin genes MUC2
      and MUC5AC.LZ and SLPI secretions were increased in these cultures. Paradoxically
      LZ mRNA was decreased, while SLPI mRNA levels were increased. Removal of T3
      selectively increased mucin secretion, MUC2 gene expression was not affected, but
      MUC5AC mRNA levels reproducibly increased, suggesting that the expression of
      these two mucin genes is differentially regulated. LZ and SLPI secretion levels
      were not significantly affected by deletion of T3 from the culture media;
      however, LZ mRNA levels were increased in the absence of T3 while SLPI transcript
      levels were not affected. Omission of the attachment substratum, type I collagen
      gel, resulted in significant increases in all 3 secretory products. MUC2 and
      MUC5AC steady state mRNA levels were not consistently affected. In contrast LZ
      and SLPI gene expression were reproducibly increased. Our studies show that
      individual factors in the epithelial environment can regulate expression of
      specific secretory cell gene products in a highly selective manner.

PMID- 9191475
TI  - Positron emission tomography in cardiovascular disease.
AB  - Positron emission tomography (PET) represents an advanced form of nuclear imaging
      technology. The use of positron emitting isotopes, such as C-11, O-15, N-13, and
      F-18 permit radiolabelling of naturally occurring compounds in the body or close
      analogues. This, combined with technical advantages of PET imaging, allow
      quantification of physiological processes in humans. PET has become established
      as the most accurate noninvasive means for the diagnosis of coronary artery
      disease using myocardial perfusion radiotracers, which include rubidium-82, N-13
      amonia, and O-15-water. These approaches have also been applied for long term
      evaluation of the effects of therapy and for the quantification of myocardial
      bloodflow. Radiolabelling of metabolic substrates, including C-11 palmitate, C-11
      acetate and F-18 flurodeoxyglucose (FDG) have permitted evaluation of myocardial
      metabolism. F-18 FDG PET imaging has been established as the best means for
      defining viable myocardium in patients with reduced ventricular function being
      considered for revascularization. FDG PET can also identify patients being
      considered for cardiac transplant, who may be candidates for revascularization.
      In this review, other applications for metabolic, autonomic nervous system and
      receptor imaging are also discussed. The availability of cardiac PET in Canada is
      currently limited. However, with the reducing costs of capital and more cost
      effectiveness data, PET may become more widely available. Cardiac PET imaging is
      established as a tremendous diagnostic tool for defining viable myocardium,
      assessment of perfusion and long term evaluation of therapy without invasive
      procedures. PET is also a vital research tool capable of evaluating flow,
      metabolism, myocardial receptors, autonomic nervous system and potentially
      radiolabelled drugs. Cardiac PET imaging will continue to provide important
      insight, expanding our understanding and treatment of patients with
      cardiovascular disease.

PMID- 9191476
TI  - A lipid clinic associated with a research laboratory working on
      dyslipoproteinemias and atherosclerosis.
AB  - BACKGROUND: Atherosclerosis is a widespread disease in affluent societies.
      Dyslipidemias and susceptibility genes enhance the likelihood of developing
      coronary artery disease, its most dreaded complication. There is a need for rapid
      transfer of advances in knowledge to the care of patients with conditions
      predisposing to atherosclerosis. A lipid clinic associated with a research
      laboratory, a 'lipid unit', provides an optimal setting to achieve this goal.
      OBJECTIVE: To describe the organization, function, usefulness and modus operandi
      of a lipid unit. DESIGN: Review of nearly 30 years' experience in directing a
      lipid unit. SETTING: A basic research laboratory associated with an outpatient
      lipid clinic and day care unit in a clinical research institute with academic
      affiliations. MEASUREMENTS: Examples of advances made within the framework of a
      lipid unit are used for illustration. RESULTS: Major advantages may be derived
      from a close interaction between clinical and laboratory staffs in a lipid unit
      and the medical community at large. Such interactions provide a strong incentive
      for research, foster discoveries of new diseases and facilitate transfer of new
      knowledge in diagnosis and treatment to patient care. A referral centre for
      complex problems allows access to unusual cases which may become a starting point
      for research and discovery. An integrated lipid unit may become a major
      contributor to medical education and community health care when a dialogue is
      established with referring physicians. CONCLUSIONS: The concept of an integrated
      lipid unit with a role in medical education and health care is viable.

PMID- 9191477
TI  - Interventions for coronary stenosis--a Canadian experience of 30 revolutionary
      years.
AB  - OBJECTIVE: To report 2324 coronary stenosis interventions (Vineberg procedures
      [VbP], coronary artery bypass graft operations [CABG] and percutaneous
      transluminal coronary angioplasties [PTCA]), in 1711 patients of a Canadian
      military hospital between 1965 and 1995 and to report their evolution and
      interaction in a historical context. DESIGN: Retrospective examination of
      clinical and angiographic findings in hard records, collected from the beginning
      for long term follow-up and later embedded in a custom-designed computer
      database. PATIENTS: Most were male, mean ages 43.2 and 43.3 years for first and
      second VbPs; 48.9 and 58.2 years for first and repeat CABGs; and 53.4 and 59.9
      years for first and repeat PTCAs, respectively; 12% of all patients were 39 years
      old or younger at the first intervention. INTERVENTIONS: There were 160 VbPs,
      1637 CABGs and 527 PTCAs. Of 1711 subjects, 74% had only one procedure, 15% had
      more than one of the same kind, and 11% had more than one of different kinds.
      MAIN RESULTS: Perioperative mortality for VbPs was 4.4%; for 'isolated' first
      CABGs it was 1.4% and 6.6% for reoperations, when other concurrent major cardiac
      procedures, excepting ventricular aneurysm repair, were excluded. It was 0.4% for
      PTCAs. Perioperative mortality for all 1761 'isolated' coronary interventions
      necessitating thoracotomy, during 30 years, was 2.4%. Angiographic follow-up
      rates were high and some findings are reported, including early postoperative
      patency rates for 5065 coronary bypass grafts, and long term follow-up data on
      graft patency and disease. CONCLUSIONS: Each intervention was used to circumvent
      or relieve coronary stenosis, in the early years when it became available and,
      later, as was most appropriate for dealing with specific clinical problems. The
      impact of advances in the evolution of these interventions on therapeutic
      decision-making is discussed. Finally, tributes are paid to those responsible for
      making these procedures possible, including a Canadian surgeon whose role was
      pivotal.

PMID- 9191478
TI  - The acute coronary ischemic syndromes--the central role of thrombosis.
AB  - The postulate that thrombotic coronary occlusion was the underlying
      pathophysiologic event in the acute coronary ischemic syndromes was developed
      over the years 1912-60. This concept prompted the development of anticoagulant
      and thrombolytic therapies and the use of acetylsalicylic acid in such patients.
      A central role for coronary thrombus came to be questioned in the 1970s and the
      use of anticoagulants dramatically decreased and thrombolytic therapy was little
      used. Coronary angiographic studies among patients during the early hours of
      evolving myocardial infarction re-established the etiologic role of coronary
      thrombosis in the acute coronary ischemic syndromes, and were supplemented by
      careful autopsy studies. The concepts of meta-analysis lead to more accurate
      interpretations of earlier randomized, controlled trials of anticoagulant,
      antiplatelet and thrombolytic therapies. Large clinical trials have provided
      confirmatory evidence and have established the benefits of antiplatelet and
      thrombolytic agents in the acute ischemic syndromes. The benefit of long term
      anticoagulation following myocardial infarction has been demonstrated, although
      the benefit during the acute in-hospital phase of myocardial infarction is still
      uncertain. Currently, clinical trials are evaluating new antithrombins,
      antiplatelet agents, and thrombolytic agents and regimens among patients with
      unstable angina, acute myocardial infarction, and undergoing angioplasty for
      complex coronary lesions.

PMID- 9191479
TI  - Evolution of the CCU from rhythm, function and protection to reperfusion and
      beyond: a personal journey and perspective.
AB  - OBJECTIVE: To trace the evolution of coronary care and the management of acute
      coronary syndromes. STUDY SELECTION: Landmark articles and selected personal
      experiences. DATA SYNTHESIS: The evolution of coronary care falls into four major
      categories and decades: the 1960s during which it was recognized that
      resuscitation from myocardial infarction through closed chest resuscitation (CPR)
      and defibrillation were possible and attention was directed towards the
      recognition and management of cardiac dysrhythmias; in the 1970s it became
      appreciated that infarct size was directly related to prognosis and modifiable.
      Hemodynamic monitoring was introduced and made significant contributions to the
      identification of prognostic subsets and the pharmacologic management of pump
      failure; thrombolytic therapy was introduced in the 1980s and has markedly
      altered the care of patients with acute myocardial infarction who have ST
      elevation. Primary angioplasty is an important therapeutic alternative especially
      in selected subsets; in the 1990s attention shifted to opportunities for
      favourable impact on ventricular remodelling after myocardial infarction, more
      cost effective therapy, enhancement of the process of care, and the
      identification of low and high risk subsets that might lead to more efficient
      diagnostic triage early after symptom presentation. CONCLUSIONS: There has been a
      profound evolution of the coronary care unit since its inception in Canada in
      1962. It has proved a remarkable environment for education and clinical
      investigation through which patient care has been substantially improved. Lessons
      learned have favourably impacted on the process of care, the creation of new
      national and international standards and a fertile environment for continuous
      future evaluation and improvement.

PMID- 9191480
TI  - Importance of outside hospital mortality as a first acute ischemic heart event:
      the Quebec Cardiovascular Study.
AB  - Among 4371 men aged 35 to 64 in 1973 who were randomly selected, living in Quebec
      City suburbs, without clinical evidence of ischemic heart disease (IHD) at entry
      and followed for 16 years, 426 had a first acute IHD event; of these, 296 had a
      nonfatal myocardial infarction (MI), 50 a fatal MI (death within four weeks of
      the acute event) and 80 an early death, ie, they died before the diagnosis of MI
      was made. Among these 80 early deaths attributed to IHD in the absence of any
      other apparent cause, 55 men died within 1 h from the onset of symptoms or were
      found dead in their bed (group A) while 25 died more than 1 h after the onset of
      symptoms (group B). In this population, a first acute IHD event carried a 31%
      (130 of 426) case fatality within the first four weeks. Groups A and B accounted
      for 42% (55 of 130) and 19% (25 of 130) of the total acute ischemic mortality,
      respectively. As expected, fatal events increased with age, but the proportion of
      early deaths over the total IHD mortality was as frequent in younger men as in
      older men. Smoking, increased systolic and diastolic blood pressure and serum
      cholesterol were associated with increased nonfatal events. A similar
      association, except for serum cholesterol, was observed for all fatal events. No
      significant risk factor profile differentiated early from late fatal events. In
      conclusion, in this population, nearly a third of men with a first IHD event
      died, most of them outside the hospital. None of the main established risk
      factors differentiated men with a fatal MI from those with an early death.

PMID- 9191481
TI  - Coronary stenting in acute myocardial infarction--patency demonstrated
      postmortem.
AB  - This report describes a patient with an acute anterior myocardial infarction
      treated by primary angioplasty and stenting of the infarct-related artery. The
      patient died 48 h later and at postmortem examination, patency of the stented
      artery was demonstrated, despite the adverse conditions which preceded death.

PMID- 9191482
TI  - A pragmatic approach to the use of angiotensin-converting enzyme inhibitors in
      acute myocardial infarction.
AB  - Which patients with an acute myocardial infarction should be treated with an
      angiotensin-converting enzyme (ACE) inhibitor and when should this treatment be
      initiated? Combining pathophysiological evidence with the findings of large
      clinical trials, it is recommended that in the postinfarction setting ACE
      inhibitors should be given only to high risk patients, ie, patients with arterial
      hypertension, patients in Killip class II or III, patients with an acute anterior
      myocardial infarction, patients with left ventricular dysfunction and patients
      with a previous myocardial infarction. Treatment should be started as soon as it
      is considered safe.

PMID- 9191483
TI  - Lower ischemic heart disease incidence and mortality among vitamin supplement
      users.
AB  - OBJECTIVE: This study assessed the relationship between vitamin supplement use
      and the occurrence of ischemic heart disease (IHD). DESIGN: A cohort study was
      conducted between 1985 and 1991 in Quebec City. In 1985, 2313 men provided
      baseline information on vitamin supplement use and IHD risk factors. Incidence of
      IHD events was ascertained over the first five years of follow-up. Cox regression
      models were used to assess the relation between vitamin supplement use and
      occurrence of IHD events while controlling for confounders. MAIN RESULTS: Vitamin
      supplement use was consistently associated with a lower incidence of IHD. The
      adjusted rate ratios and their 95% confidence intervals were: 0.31 (0.09-0.99)
      for IHD death, 0.53 (0.24-1.11) for MI, 0.76 (0.44-1.65) for angina and 0.73
      (0.44-1.22) for a first IHD event. The associations were stronger for IHD death
      and myocardial infarction, two events assessed with high validity. The inverse
      association with IHD was more consistent for vitamin E than for any other
      vitamin. CONCLUSION: This study suggests that the inverse association between
      vitamin supplement use and IHD is real. The causal nature of the association can
      only be demonstrated in the context of a randomised intervention trial such as
      the HOPE study.

PMID- 9191484
TI  - Viral myocarditis: balance between viral infection and immune response.
AB  - Myocarditis is an inflammatory disorder of the heart muscle, and is often
      underdiagnosed in clinical practice. It presents more dramatically in the young
      with acute heart failure and more insidiously in adults with chronic dilated
      cardiomyopathy. The etiology is most often viral in North America, with a wide
      spectrum of natural history. The majority of patients recover spontaneously, but
      those with persistent ventricular dysfunction face a 20% one-year mortality.
      Myocarditis initiates as viral disease, and molecular techniques have confirmed
      viral persistence. The immune response follows as a two-edged sword-both
      inadequate and excessive immune responses lead to disease. Finally, the myocyte
      is the target of the above processes, and expresses molecular, cytokine and
      vascular changes that lead to dilated cardiomyopathy and heart failure. The gold
      standard for diagnosis still relies on the overly strict Dallas criteria for
      evaluating myocardial biopsies. Molecular techniques are playing an increasingly
      important role in both diagnosis and prognosis. Clinical suspicion is still the
      key towards an early diagnosis. Treatment must be early and persistent-generally
      supportive initially, with immunosuppression now playing a secondary role in
      temporizing those with exuberant immune response. Newer treatments for dilated
      cardiomyopathy such as amlodipine and carvedilol are equally appropriate for
      postmyocarditis patients. Future treatment may involve specific biological
      agents, immune therapy, antiviral strategies and molecular gene therapy.

PMID- 9191485
TI  - Reverse cholesterol transport: its contribution to cholesterol catabolism in
      normal and disease states.
AB  - OBJECTIVES: To review the reverse cholesterol transport (RCT) model and its
      contribution to cholesterol catabolism in normal and disease states. DATA
      SOURCES: Pertinent articles were identified through a MEDLINE search of the
      English language literature from 1983 to 1995, followed by a manual search of the
      bibliographies of pertinent articles. STUDY SELECTION: Review articles,
      laboratory and clinical studies and case reports. DATA EXTRACTION: The physiology
      of the RCT pathway as well as alterations observed in individuals with diseases
      or lifestyle changes were reviewed. DATA SYNTHESIS: Data were derived mainly from
      laboratory studies and clinical observations. The RCT model is proposed to
      explain the removal of excess cholesterol from extrahepatic tissues and its
      delivery to liver for catabolism. This involves several regulated steps mediated
      by the plasma apolipoproteins and two key enzymes, lecithin:cholesterol
      acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). In essence
      free cholesterol in peripheral tissues is taken up by nascent high density
      lipoprotein (HDL) particles, converted to cholesteryl esters (by LCAT), and then
      transferred to apo B-containing lipoproteins (by CETP) for hepatic removal.
      Altered cholesterol catabolism may occur in individuals with disorders of a
      genetic or acquired nature as well as lifestyle changes, as a result of
      alterations in one of several of the putative steps or enzymes involved in RCT.
      CONCLUSIONS: The proposed antiatherogenic role of RCT remains to be validated as
      a review of the possible alterations noted in various disorders showed
      conflicting results in atherogenic propensity.

PMID- 9191486
TI  - Doppler-derived diastolic indices in dilated cardiomyopathy: a hemodynamic
      evaluation relating pre- and afterload parameters to flow velocity.
AB  - OBJECTIVE: To explain the well known finding of a normal early diastolic filling
      velocity in advanced grade heart failure due to dilated cardiomyopathy (DCM)
      exclusively by hemodynamics and to relate Doppler-flow velocity parameters to
      indices representing pre- and afterload. DESIGN: DCM was hypothesized to be a
      disorder in which pre- and afterload contribute in equal proportion to cardiac
      insufficiency independently from ischemic impairment of relaxation. PATIENTS:
      Twenty patients with DCM were enroled in the study after definitive exclusion of
      coronary and valvular heart disease. METHODS: Diastolic transmitral and
      transtricuspid Doppler readings and hemodynamic measurements were done
      simultaneously by two blinded observers. A Swan-Ganz catheter was employed. MAIN
      RESULTS: Simple and multiple regression analyses revealed early diastolic filling
      velocity to depend on hemodynamic parameters representing afterload. Pulmonary
      capillary wedge pressure (PCWP) was found to be directly related to early
      diastolic filling velocity. An inverse relation between early diastolic filling
      velocity and parameters representing afterload (systemic vascular resistance and
      mean arterial pressure) was demonstrated; however the most significant
      correlation using multiple regression analysis was shown between mitral early
      diastolic peak-flow velocity (dependent) and PCWP as well as systemic vascular
      resistance index (independents) (r = 0.75; P < 0.001). Correspondingly, the
      transtricuspid early diastolic peak-flow velocity was shown to be related to the
      equilibrium of right atrial pressure and pulmonary vascular resistance index. The
      atrial diastolic flow velocity parameters were found not to be related to
      hemodynamic indices. CONCLUSION: A definitive but not one-to-one relationship
      between early diastolic Doppler-flow indices and hemodynamic parameters was
      defined. A functional coupling of pre- and afterload can be considered the main
      determinant of early diastolic filling velocity in DCM.

PMID- 9191487
TI  - Left ventricular diastolic function in young men with high normal blood pressure.
AB  - OBJECTIVE: Abnormalities in left ventricular (LV) diastolic filling have been
      reported in hypertensive patients. This study was designed to compare LV
      diastolic filling between individuals with high normal blood pressure (HNBP) and
      optimal blood pressure (OBP). SUBJECTS AND DESIGN: From a survey of 219 young
      male individuals (age 21 +/- 0.1 years), two groups were selected according to
      their BP (group A: systolic BP [SBP] 120 mmHg and diastolic BP [DBP] 80 mmHg, n =
      23 and group B: SBP 130 to 139 mmHg and/or DBP 85 to 89 mmHg, n = 21). Subjects
      habits, anthropometric characteristics, LV structure and systolic and diastolic
      function were compared. RESULTS: No differences were detected between the two
      groups in habits, systolic function or early diastole. LV mass index (LVMI) was
      higher in group B (103.6 +/- 4.58 g/m2 versus 90.49 +/- 3.27 g/m2 in group A, P <
      0.05), though the values were not high enough to indicate LV hypertrophy. The
      pattern of LV late filling was different between the two groups. The peak late
      diastolic flow velocity (A) was 0.45 +/- 0.02 m/s in group B and 0.52 +/- 0.03
      m/s in group A (P < 0.05). The early peak velocity (E):A ratio was 1.82 +/- 0.08
      in group A and 1.59 +/- 0.08 in group B (P < 0.05). The early filling fraction
      also demonstrated a significant shift to more prominent late diastolic filling in
      group B (0.68 +/- 0.01% versus 0.73 +/- 0.01% in group A, P < 0.05). This pattern
      in LV filling did not correlate to inheritance, age, sex, heart rate, habits or
      body mass index. CONCLUSIONS: This shift in filling pattern to a late flow in
      young men with HNBP seemed to be an early indicator of an increased dependence of
      LV filling on atrial contraction and may reflect an impairment in LV relaxation.

PMID- 9191488
TI  - Interventional cardiology for the adult patient with congenital heart disease:
      the Toronto Hospital experience.
AB  - Interventional cardiac procedures for patients with congenital heart disease,
      developed for the pediatric patient, have been adapted for the adult patient. In
      this review these unique procedures are reviewed with emphasis on the experience
      at The Toronto Congenital Cardiac Centre for Adults. Procedures directed to
      closing shunts include: occlusion of patent ductus arteriosus, coil embolization
      of aorto-systemic collaterals, coronary fistulas, and Blalock-Taussig shunts, and
      early attempts at nonsurgical occlusion of atrial septal defects. Balloon
      dilation procedures include management of pulmonary valve stenosis, peripheral
      pulmonary artery stenosis, and more recently the application of stents in
      dilation of coarctation of the aorta. Development of interventional techniques
      for adult congenital heart disease involves a diverse number of procedures which
      provide successful nonsurgical options for many patients with congenital heart
      disease.

PMID- 9191489
TI  - Use of the newer antiarrhythmic drugs in patients with supraventricular
      tachyarrhythmias: let's not throw out the baby with the bath water.
AB  - Although recent advances have expanded the therapeutic choices for patients with
      supraventricular tachyarrhythmias, most of these patients will still require
      either short or long term treatment with antiarrhythmic drugs. Unfortunately,
      some practitioners have reacted to recent reports emphasizing the hazards of
      antiarrhythmic drug therapies by adopting an attitude of avoidance of these
      therapies. Although critical analyses of available data indicate that many
      antiarrhythmic drugs may have an unfavourable risk-benefit balance in patients
      with low risk arrhythmias who also have atherosclerotic heart disease and/or
      congestive heart failure, the same cannot be said for patients with high risk
      arrhythmias, for patients without atherosclerotic heart disease or congestive
      heart failure, or for patients whose symptoms require antiarrhythmic therapy to
      prevent physical and emotional disability despite a small risk of therapy. These
      patients are not benefits by the prevalent nihilistic attitude of antiarrhythmic
      drug avoidance. The purpose of this review is to provide an electrophysiologic
      background for the rational selection of antiarrhythmic drug therapy for patients
      with supraventricular tachyarrhythmias with an accent of the newer agents that
      have been demonstrated to be useful for this purpose.

PMID- 9191490
TI  - Atrial septal defect in adults.
AB  - BACKGROUND: The value of operation of atrial septal defect (ASD) in adults,
      especially after 40 years, is still discussed. METHODS AND RESULTS: In 1994-95 57
      adults with unoperated ASD were examined clinically, echocardiographically and in
      75% by catheterization. Type primum was present in 11%, type secundum in 77% and
      sinus venosus in 11%. Group A comprised 28 patients aged 20 to 40 years (average
      29), group B comprised 29 patients aged 40 to 62 years (average 51). The groups
      (B:A) did not differ in pulmonary to systemic flow (Qp/Qs) (2.4:2.2) or pulmonary
      arteriolar resistance (PAR) (group B 2 U.m2, group A 1.7 U.m2), the older
      patients had worse New York Heart Association (NYHA) classification, more
      frequent tricuspid regurgitation (group B 96%, group A 45%), significantly larger
      right ventricles and pulmonary arteries, higher mean pulmonary artery pressure
      (group B 26 mmHg, group A 17 mmHg) and right ventricle end-diastolic pressure
      (RVEDP group B 10, group A 8.8 mmHg). All defects larger than 10 mm by
      transesophageal echocardiography (TEE) had Qp/Qs 1.5 or more. Forty patients were
      operated with zero mortality, in three cases by minithoracothomy.
      Postoperatively, 50% of group A and 63% of group B felt better, NYHA
      classification was significantly better in both groups. Tricuspid regurgitation
      decreased in both groups as well as the size of right ventricle. The size of the
      left ventricle enlarged after operation in group A. CONCLUSION: This study
      suggests to operate adults with ASD larger than 10 mm by TEE with signs of right
      ventricle overload and/or Qp/Qs 1.5 or more, who have normal PAR. Operative
      mortality was zero in both age groups, the functional repair was better in
      younger patients (under 40 years).

PMID- 9191491
TI  - Recurrent unexplained syncope: diagnostic and therapeutic approach.
AB  - Patients with syncope of unknown etiology may suffer from recurrent disability.
      Syncopal episodes are often too infrequent and unpredictable for detection with
      conventional ambulatory monitoring techniques. A symptom-rhythm correlation is a
      frequently unattainable gold standard in many patients. Clinicians must often
      rely on the results of laboratory testing to make an inferential determination of
      the etiology of spontaneous syncope. Electrophysiological testing has a role in
      patients with structural heart disease and suspected ventricular arrhythmias, but
      is negative in 14% to 70% of patients studied and has a limited role in patients
      without structural heart disease. The external loop recorder is an ambulatory
      device worn for weeks or even months that freezes the preceding rhythm strip
      after an episode of spontaneous syncope. This device is useful in patients with
      frequent symptoms but is hampered by lack of patient compliance and technical
      limitations. In the absence of a diagnosis after extensive testing, an empirical
      trial based on index of suspicion may be warranted. This may include implantation
      of a pacemaker for suspected bradycardia or empirical therapy directed at a
      tachycardia. Finally, recent reports of an insertable loop recorder suggest a
      high diagnostic yield with a broad spectrum of etiologies in patients with
      recurrent syncope in spite of negative noninvasive and electrophysiological
      testing. In the future, such a device may assume a prominent role in the
      investigation of syncope.

PMID- 9191492
TI  - The promise and practice of cardiovascular risk reduction: a disease management
      perspective. Clinical Quality Improvement Network (CQIN) Investigators.
AB  - OBJECTIVE: Interpretive analysis of epidemiological, clinical trials and practice
      pattern data for cardiovascular risk reduction in the contemporary setting of
      unprecedented demographic changes. DATA SOURCES: Literature review and audit
      results of the Clinical Quality Improvement Network (CQIN). DATA SYNTHESIS:
      Coronary artery disease (CAD) is the largest single cause of death in Canada. CAD
      is age-related and the population is rapidly ageing, a combination that threatens
      an epidemic of future CAD events. Epidemiological data demonstrate a direct
      relation of CAD risk and serum cholesterol levels and no threshold cholesterol
      level below which there is no CAD risk. The epidemiological data also suggest CAD
      risk can be reduced by lowering serum cholesterol and this hypothesis has now
      been incontrovertibly confirmed by repeated randomized clinical trials. Most
      recently, reduction of all-cause mortality with cholesterol-lowering therapy in
      high risk subjects has also been confirmed. Despite the overwhelming trials and
      epidemiological evidence, CQIN effectiveness analyses reveal far from optimal
      risk assessment and management practices among high risk patients. CONCLUSIONS:
      Serum cholesterol is directly related to CAD risk. Reduction of cholesterol
      reduces CAD, and all-cause, mortality in high risk patients. There is a large
      window of opportunity to improve lipid-lowering practices, and patient outcomes,
      for the most deadly diseases in our society.

PMID- 9191493
TI  - Economic impact of cardiovascular disease in Canada.
AB  - OBJECTIVE: To estimate the total cost of cardiovascular disease in Canada.
      DESIGN: Prevalence-based study estimating disease-related costs generated by
      individuals with cardiovascular disease in 1994, from a societal viewpoint. The
      human capital approach was used to estimate the value of lost productivity due to
      illness. SETTING: Canada. OUTCOME MEASURES: First, direct costs, in terms of
      expenditures on hospital care, other institutions, physician services, other
      health professionals, drugs, research and other items; and second, indirect
      costs, in terms of lost productivity due to premature mortality or disability.
      MAIN RESULTS: The total cost of cardiovascular disease was $18.0 billion in 1994,
      with direct and indirect cost components at $10.4 and $7.6 billion, respectively.
      Based on the sensitivity analysis, the lower and upper bounds were $14.1 and
      $20.4 billion, respectively. CONCLUSIONS: This study highlights the scope and
      magnitude of cardiovascular disease through its economic consequences. While the
      figures calculated herein do not give an indication of the appropriateness of
      current health expenditures on cardiovascular disease, they provide guidance in
      the setting of national priorities for research and prevention activities.

PMID- 9191494
TI  - Basic research: a continuing imperative for clinical practice.
AB  - Basic biomedical research is essential to progress in prevention and treatment of
      disease and often results in massive economic benefits to society. Despite this,
      the financial and institutional bases that support basic scientists is under
      threat in our rapidly changing society. Polio vaccination is cited as an
      outstanding example of both an unexpected outcome of basic research and an
      enormous economic return to society on the original research investment.
      Interventional catheterization and the potential of successful gene therapy for
      cystic fibrosis are further examples of great potential economics benefits
      flowing from fundamental research. One great impediment to adequate investment in
      basic research is the lack of understanding of its nature. Canadian scientists
      need to be much more active in bridging the cultural gap between science and
      society and especially in educating national policy makers about the major
      economic benefits resulting from previous investments in basic biomedical
      research.

PMID- 9191495
TI  - Mechanical circulatory support as a bridge to transplantation: past, present and
      future.
AB  - OBJECTIVE: Historical and state-of-the-art review of clinical mechanical
      circulatory assist and replacement devices. Recent clinical experience at the
      University of Ottawa Heart Institute with various mechanical circulatory assist
      devices as a bridge to transplant, and experimental results with the development
      and testing of a new electrohydraulic ventricular assist device, are described in
      detail. DATA SOURCES: A Medline search of the English literature from 1980 to
      1996 was done using the following words: artificial heart; ventricular assist
      device; and transplantation. STUDY SELECTION: Papers were selected to provide
      both a historical perspective and an overview of the current status and future
      prospects of mechanical circulatory assist devices and artificial hearts. DATA
      SYNTHESIS: Since the implantation in animals of the first devices in the 1960s
      and 70s, there have been astounding improvements in design, available materials
      and implementation of these devices. Increases in the understanding and
      management of thrombogensis and immunosuppressive drugs as well as developments
      in the fields of miniaturization, pumps and power sources will lead to
      concomitant improvements in these devices. CONCLUSIONS: The use of these devices
      has become an accepted treatment for end-stage heart disease. Additional
      development and testing is required to address persistent complications in most
      models if they are to become alternatives to cardiac transplantation. The basis
      of the future successes is dependent on both technological refinements in the
      developments of new devices and on continued research into the physiological
      effects of mechanical circulatory support. However, these devices are used both
      as a bridge to recovery and a bridge to cardiac transplant and it is expected
      that they will be used increasingly to provide permanent circulatory assistance
      or replacement.

PMID- 9191496
TI  - The clinical case report: a tool for hypothesis generation.
AB  - The clinical case report is generally limited to a description of unusual
      examples of the complications of disease or responses to therapy. However, it can
      also be used to present novel hypotheses which have been derived from individual
      cases. Two examples of this latter genre are presented and updated. These are
      Syndrome X and the stiff left atrial syndrome. In both instances, general and
      novel formulations were derived from single cases. With respect to Syndrome X, a
      hypothesis was generated that the chest pain and ST abnormalities in these
      patients represent excess activation of adenosine A1 receptors in the absence of
      myocardial ischemia. With respect to the stiff left atrial syndrome, recognition
      of the first case led to the recognition of the problem in many others. Now, a
      variant of the syndrome has been recognized in which mitral regurgitation is also
      present. In addition, the possibility that tricuspid annuloplasty may rescue
      patients dying of cardiac cachexia due to right heart failure caused by combined
      pressure and volume overload of the right ventricle is outlined.

PMID- 9191497
TI  - Endurance athletes, insulin secretion and muscle quality.
AB  - OBJECTIVE: To study how muscle ubiquinone content (MUQ) and percentage slow
      twitch (%ST) of muscle fibres in the thighs of male healthy subjects with a low
      or high insulin response to glucose infusion tests (GIT) affected blood glucose
      control (BGC). DESIGN: People with a low insulin response were recruited from
      sedentary low insulin responders (LIRs) or endurance trained LIRs. A group of men
      with high insulin response (HIRs) was used for comparison. In addition to GIT,
      glucose metabolism was estimated with somatostatin-insulin-glucose infusion tests
      (SIGIT; insulin sensitivity). RESULTS: Sedentary LIRs and HIRs had low exercise
      capacities and an increased BGC with increased exercise capacity. BGC in
      sedentary LIRs, in contrast to HIRs increased with MUQ and/or %ST. Only trained
      LIRs showed an elevated peripheral insulin receptor sensitivity despite a
      decreasing MUQ with %ST. This relationship indicated muscle metabolic lesions in
      trained LIRs with a high %ST and additional compensatory BGC mechanisms in
      trained LIRs. CONCLUSION: BGC in HIRs was maintained with insulin and an exercise
      regulated insulin sensitivity, BGC in sedentary LIRs with a good muscle membrane
      and metabolic control due to adequate MUQ depots, and BGC in trained LIRs with an
      elevated insulin sensitivity. Trained LIRs rich in %ST had a low MUQ indicative
      of muscle lesions such as from 'overuse injury'.

PMID- 9191498
TI  - Heart failure and Starling's Law of the heart.
AB  - Coronary artery disease and ischemic myocardial damage form the most common cause
      of failure of the heart to pump enough blood for oxygenation of the body at a
      healthy blood pressure and at a low pressure in the veins. This paper gives an
      overview of the mechanisms involved in excitation-contraction coupling which are
      important to control of the force of the heartbeat. The inability of the heart in
      failure to eject a sufficient amount of blood in order to meet the needs of the
      body is thought to result from molecular changes in cardiac cells causing
      decreased active (systolic) force and impaired (diastolic) relaxation together
      with a greater stiffness of the remodelled ventricular wall. The failure to
      generate a forceful contraction is in part a consequence of derailment of the
      processes in the failing cardiac cells to manipulate calcium ions, despite the
      increased stimulus from nervous and hormone systems to enhance cardiac
      performance. By lack of adequate release and uptake of calcium ions, the amount
      of mechanical work that can be put out by the heart muscle is diminished and the
      heart may fail. Uptake of calcium ions by the intracellular store-the
      sarcoplasmic reticulum-is impaired in congestive heart failure probably as result
      of inadequate gene expression. In consequence, the amount of calcium that is
      released during each heartbeat is less than normal, thus force is reduced; in
      addition, the positive response of force to increased heart rate is lost. In
      normal heart muscle, the response of the contractile filaments to calcium ions
      depends strongly on sarcomere length thus explaining Starling's Law of the heart.
      Recent evidence suggests that this sensitivity is largely lost in congestive
      heart failure thereby reducing the effectiveness of stretch of cardiac cells on
      the mechanical output. The reduction of the maximal velocity of shortening of the
      cardiac sarcomere in heart failure is not well understood, but may in part be
      related to changes in the internal load as a result of changes in visco-elastic
      components of the myocardium Lastly, the effect of longstanding sympathetic drive
      to the heart during the development of heart failure induces a loss of
      sensitivity of the myocardium to catecholamines by loss of beta 1 receptors and
      partial uncoupling of the beta receptors from production of cyclic AMP; hence the
      effect of sympathetic activation is diminished and the heart has to rely more on
      Starling's Law. Increase of the filling pressure of the left ventricle may in
      part accommodate the ongoing demands of the body. However, in the case of a
      stenosed coronary arterial system, the increased end-diastolic pressure carries
      the substantial risk of aggravating pre-existent myocardial ischemia.

PMID- 9191499
TI  - Ventricular interaction and venous capacitance modulate left ventricular preload.
AB  - The concept of left ventricular (LV) 'preload' has seemed simple and
      straightforward. Similarly, the capacitance function of the veins seemed to be
      defined, in spite of the fact that 'venous return' might be said to be increased
      in heart failure when it was obvious that cardiac output was substantially
      decreased. In studies during the past several years, we have demonstrated that
      pericardial pressure, as a major modulator of ventricular interaction, must be
      accounted for before preload, myocardial compliance or contractility can be
      assessed reliably. Also, using a new conceptual model based on venous pressure
      volume relations that explains how changes in venous capacitance modulate
      ventricular preload, we have defined the comparative capacitance-conductance
      effects of various vasodilators in a model of heart failure. We conclude that
      left ventricular preload is significantly modulated by both changes in
      ventricular interaction and venous capacitance. To optimize the care of patients
      with heart disease, it is important to understand both these mechanisms.

PMID- 9191500
TI  - Sarcoplasmic reticular Ca2+ pump ATPase activity in congestive heart failure due
      to myocardial infarction.
AB  - OBJECTIVE: Earlier studies have shown a depression in the sarcoplasmic reticular
      (SR) Ca2+ uptake and gene expression in Ca2+ pump ATPase protein in congestive
      heart failure subsequent to myocardial infarction. It is the objective of this
      study to understand further the mechanisms of depressed SR Ca2+ pump activity in
      the failing heart. METHODS: Heart failure in rats was induced by occluding the
      left coronary artery for 16 weeks and the viable left ventricle was processed for
      the isolation of SR membranes. Sham-operated animals were used as control. The
      characteristics of SR Ca2+ pump ATPase in the presence of different
      concentrations of K+, Ca2+ and ATP were examined and the purity of these
      membranes was monitored by determining the marker enzyme activities. In addition
      to measuring changes in cyclic adenosine monophosphate (cAMP) protein kinase and
      Ca(2+)-calmodulin induced phosphorylation, alterations in SR phospholipid
      composition as well as sulfhydryl (SH) group content were investigated. RESULTS:
      Ca(2+)-stimulated ATPase activity, unlike Mg(2+)-ATPase activity, was depressed
      in the left ventricular SR from failing hearts as compared to control. The
      decrease in Ca(2+)-stimulated ATPase activity was seen at different
      concentrations of Ca2+, K+ and ATP but no changes in the affinities of the enzyme
      for Ca2+ and ATP were evident. The SR Ca(2+)-stimulated ATPase activities in the
      presence of both cAMP-dependent protein kinase and Ca(2+)-calmodulin were
      markedly decreased in the failing hearts when compared to control preparations.
      Furthermore, the 32P incorporation in the presence of cAMP-dependent protein
      kinase or Ca(2+)-calmodulin was also reduced in the experimental heart SR
      membranes. The phospholipid composition of the SR membranes from the failing
      heart was markedly altered. No changes in SH-group or the degree of cross
      contamination with other membranes were apparent in the failing heart SR.
      CONCLUSIONS: These results suggest that abnormalities in membrane phospholipid
      composition and phosphorylation of the enzyme may partly explain the observed
      depression in SR Ca2+ pump ATPase activity in heart failure following myocardial
      infarction.

PMID- 9191501
TI  - The sodium-hydrogen exchange system in the heart: its role in ischemic and
      reperfusion injury and therapeutic implications.
AB  - OBJECTIVES: To review evidence supporting a role for sodium-hydrogen exchange
      (Na/H exchange) in mediating myocardial ischemic and reperfusion injury, and to
      outline clinical implications in terms of the development of novel
      cardioprotection strategies. DATA SOURCES: Various sources were used including
      MEDLINE and Reference Update. Only articles written in the English language were
      used. DATA EXTRACTION: A wide range of publications dealing with cardiac injury
      and particularly studies involving intracellular pH regulation and Na/H exchange
      activity. The vast majority of papers cited were published since 1986, with a
      large percentage appearing within the past five years. DATA SYNTHESIS: Na/H
      exchange is a major mechanism for restoration of intracellular pH after ischemia,
      although its activation during both ischemia and reperfusion has been shown to be
      involved in a paradoxical induction of cell injury. This likely reflects the fact
      that activation of the exchanger is closely coupled to sodium influx and, as a
      consequence, to elevation in intracellular calcium concentrations through sodium
      calcium exchange. In addition to intracellular acidosis, other factors can
      stimulate the exchanger, including various autocrine and paracrine factors such
      as endothelin-1 and activation of alpha 1 adrenergic receptors, both of which
      likely act through signal transduction processes including activation of protein
      kinase C. Although at least 5 Na/H exchange isoforms have been identified, it
      appears that subtype 1, termed NHE-1, is the predominant isoform in the mammalian
      myocardium. Effective pharmacological inhibitors of Na/H exchange, including
      those that are NHE-1 specific, have been developed. These have been extensively
      demonstrated to protect the ischemic and reperfused myocardium, as shown by
      improved systolic and diastolic function, preservation of cellular ultrastructure
      and reduced incidence of arrhythmias. Moreover, the salutary effects of these
      agents have been demonstrated by a variety of experimental models and animal
      species, suggesting that the role of Na/H exchange in mediating injury is not
      species-specific. CONCLUSION: Na/H exchange is an important target for
      pharmacological intervention in attenuation of ischemia- and reperfusion-induced
      cardiac injury. Coupled with the low potential for toxicity by the agents, Na/H
      exchange inhibition could emerge as an effective therapeutic strategy in cardiac
      disorders, particularly involving conditions associated with ischemia and
      reperfusion.

PMID- 9191502
TI  - Superoxide dismutase and catalase in protection of cardiopulmonary bypass-induced
      cardiac dysfunction and cellular injury.
AB  - BACKGROUND: Cardiac dysfunction following cardiopulmonary bypass (CPB) is well
      known. Various possible sources for increased levels of oxygen free radicals
      (OFRs) exist during CPB and OFRs depress cardiac function. Postpump (following
      CPB) cardiac dysfunction may be due to increased levels of OFRs. METHODS: This
      study investigated the effects of cold crystalloid cardioplegia with and without
      superoxide dismutase (SOD) and catalase (CAT) on cardiac function (cardiac index
      [CI], left ventricular work index [LVWI]), cardiac contractility (+dp/dt,
      +dp/dt/PAW [pulmonary arterial wedge pressure], +dp/dt/LVEDP [left ventricular
      end-diastolic pressure]), diastolic compliance (-dp/dt), OFR-producing activity
      of polymorphonuclear leukocytes (PMNL-CL); creatine kinase (CK) and MB isoenzyme
      of CK (MBCK), malondialdehyde (MDA), and white blood cells (WBC) and PMNLs from
      coronary sinus blood; and lactate levels in arterial blood in anesthetized dogs
      at various times (up to 90 mins) of reperfusion following 90 mins of hypothermic
      ischemic cardiac arrest. The dogs were divided into three groups: group I, sham
      bypass; group II, cold crystalloid cardioplegic cardiac arrest; group III,
      similar to group II but received SOD and catalase treatment. RESULTS: Postpump
      decreases in cardiac function, contractility and diastolic compliance were
      associated with increases in PMNL-CL activity, blood MDA, plasma CK and MBCK, and
      plasma lactate, and decreases in WBC and PMNLs. Prevention of postpump cardiac
      dysfunction (function and contractility) by SOD and CAT was associated with
      restoration in PMNL-CL activity, plasma CK and MBCK activity, and blood MDA
      towards control values although not complete. The levels of plasma lactate, total
      WBC and PMNLs were similar in group II and group III. CONCLUSIONS: These results
      suggest that postpump depression of cardiac function and contractility could be
      due to increased levels of OFRs and that SOD and CAT scavengers of superoxide
      anion and hydrogen peroxide respectively may be effective in preventing postpump
      cardiac dysfunction.

PMID- 9191503
TI  - Responses of heart function and intracellular free Ca2+ to phosphatidic acid in
      chronic diabetes.
AB  - OBJECTIVE: In view of the crucial role of phosphatidic acid (PA) in signal
      transduction and Ca(2+)-handling in myocardium, it was the objective of this
      study to examine the effects of PA on cardiac contractile force and intracellular
      free Ca2+ in control and chronic diabetic rats. METHODS: Diabetes was induced in
      rats by a single intravenous injection of streptozotocin (65 mg/kg.) and the
      animals were used for experiments eight weeks after the injection. Heart function
      was measured by using the isolated perfused heart preparations, and values for
      systolic pressure, diastolic pressure, rate of contraction (+dP/dt) and rate of
      relaxation (-dP/dt) were monitored. Intracellular free Ca2+ in cardiomyocytes was
      estimated by employing Fura-2/AM method. RESULTS: PA (5 x 10(-8) to 1 x 10(-5) M)
      produced a concentration-dependent increase in +dP/dt and -dP/dt in the isolated
      heart; however, these responses were significantly attenuated in diabetic hearts.
      ATP also caused a positive inotropic effect at concentrations of 1 x 10(-5) to 1
      x 10(-4) M but the magnitude of these responses was similar in both control and
      diabetic groups. Using freshly isolated cardiomyocytes and Fura-2 technique, PA
      (1 x 10(-6) to 1 x 10(-4) M) was observed to evoke a concentration-dependent
      increase in [Ca2+]i in both control and diabetic groups. The EC50 and EC95 values
      for PA were not different but the maximum increase of [Ca2+]i in diabetic hearts
      was significantly lower in comparison to the control group (152 +/- 41 versus 304
      +/- 56 nM). On the other hand, no difference in the increase of [Ca2+]i due to
      ATP or potassium chloride was seen between control and diabetic cardiomyocytes.
      Adrenaline pretreatment enhanced [Ca2+]i responses to ATP and PA in both groups;
      however, the PA-induced increase in [Ca2+]i, unlike the ATP-induced increase, was
      lower in the diabetic group compared to the control cells with similar
      pretreatment with adrenaline. The diminished increase in [Ca2+]i due to PA was
      also observed in cardiomyocytes obtained from rats in which diabetes was induced
      by intravenous alloxan (65 mg/kg). CONCLUSIONS: PA induced [Ca2+]i mobilization
      and positive inotropic response were depressed in diabetic heart; this defect in
      the signal transduction mechanism may contribute to the lower tonic responses of
      certain inotropic agents in chronic diabetes.

PMID- 9191504
TI  - Anti-free radical mechanisms in captopril protection against reperfusion injury
      in isolated rat hearts.
AB  - OBJECTIVE: Captopril, an angiotensin-converting enzyme (ACE) inhibitor, is known
      to modulate ischemia-reperfusion injury in the isolated hearts. This study was
      designed to examine the involvement of anti-free radical mechanisms in this
      protection. METHODS: Isolated perfused rat hearts were subjected to 60 mins of
      global ischemia and 30 mins of reperfusion with or without captopril (100
      mumol/L). Myocardial resting tension and contractile force were recorded. At the
      end of reperfusion, hearts were analyzed for the activities of antioxidant
      enzymes, superoxide dismutase, glutathione peroxidase and catalase, as well as
      for the extent of lipid peroxidation. Another potent ACE inhibitor, enalapril
      (100 mumol/L) was used for comparison. RESULTS: Captopril significantly improved
      the recovery of contractile function as well as attenuated the rise in resting
      tension in the ischemic-reperfused hearts as compared to the control. Captopril
      exposed ischemic-reperfused hearts showed an increase in the activity of
      superoxide dismutase with no change in glutathione peroxidase and catalase enzyme
      activities. Lipid peroxidation at the end of reperfusion was significantly
      attenuated in the captopril-exposed hearts compared to the control. Enalapril had
      no protective effect against ischemia-reperfusion induced contractile failure or
      rise in resting force. CONCLUSIONS: These results suggest that cardioprotection
      by captopril, against ischemia-reperfusion injury, may involve an anti-free
      radical mechanism independent of its ACE inhibition property.

PMID- 9191505
TI  - Effect of transthoracic electric current on the coronary circulation of the dog.
AB  - OBJECTIVE: In vitro experiments have shown that an electric field changes
      coronary vascular resistance (CVR) tone and damages the vascular endothelium. The
      effect of transthoracic electric current in dogs on the vasodilatory responses
      mediated through the endothelium and reactive hyperemia were studied. The manner
      of delivery of the electric current was similar to that used clinically during
      cardiac resuscitation. DESIGN: Eight mongrel dogs of either sex weighing between
      15 and 22 kg were anesthetized with sodium pentobarbital. The lungs were
      mechanically ventilated and the thorax was opened. Circumflex coronary flow was
      measured with an electromagnetic flowmeter. Mean aortic pressure and the heart
      rate were kept constant and left ventricular systolic and diastolic pressures did
      not change during the procedures. The changes in CVR produced by different
      intracoronary doses of acetylcholine and reactive hyperemia to 10 and 30 s of
      circumflex coronary occlusion were measured before and after the transthoracic
      delivery of five synchronized electric shocks, 300 J each 1 min apart. MAIN
      RESULTS: CVR decreased by 32.8 +/- 2.1% (P < 0.01) from the effects of the
      electric shocks in spite of no changes in heart rate, ventricular systolic and
      diastolic pressures nor left ventricular oxygen consumption. After the delivery
      of the electric shocks, the vasodilatory response to acetylcholine decreased by a
      mean value of 35.9 +/- 2.6% for the different doses (P < 0.001) and reactive
      hyperemia decreased by 42.5 +/- 5.5% (P < 0.001) and by 31.5 +/- 9.6% (P < 0.02)
      for the 10 and 30 s occlusion duration, respectively. The intracoronary infusion
      of sodium nitroprusside decreased the coronary vascular resistance to a minimal
      value lower than that obtained by the maximal dose of acetylcholine but similar
      to before and after the passage of the electrical current revealing the
      preservation of the coronary vasodilatory reserve after the electrical shocks.
      CONCLUSIONS: These results show that transthoracic electrical shocks as used
      clinically induce coronary vasodilation but simultaneously produce endothelial
      dysfunction.

PMID- 9191506
TI  - Cardiac manifestations of Lyme disease.

PMID- 9191507
TI  - Pathology of sudden death in the young.
AB  - Sudden death is a relative concept, but generally refers to death occurring soon
      after symptom onset. In this review, cardiac causes of sudden death, designated
      coronary and noncoronary, are addressed. In the coronary category, coronary
      artery anomalies and altered coronary tone are discussed, while myocardial
      causes, valvular causes, aortic dissection and conduction system are outlined as
      part of noncoronary causes of sudden death. Sudden death in athletes and
      exercising youth also receives special comment.

PMID- 9191508
TI  - Sudden cardiac death in the young.
AB  - This review summarizes the clinical aspects of sudden cardiac death in the
      pediatric population. The scope of the problem is defined by examining findings
      from autopsy series and from clinical series of survivors of out-of-hospital
      cardiac arrest. Representative lesions from different etiological categories
      serve as discussion points.

PMID- 9191509
TI  - Sudden cardiac death in the adult with congenital heart disease.
AB  - Preliminary results of a review of sudden cardiac death in the adult with
      congenital heart disease were presented at the Canadian Adult Congenital Heart
      (CACH) Network meeting during the Canadian Cardiovascular Society's annual
      meeting in October 1994. Of 125 patients who were known to have died, sufficient
      details were available for 92 to determine the circumstance of death. Sudden
      death occurred in 23 patients (estimated incidence 5.3 per 1000 patients followed
      per year) at an average age of 33.5 +/- 11.9 years. Surgical procedures included
      intracardiac repair in 12, palliative procedures in only six and no cardiac
      surgery in six. Nine patients with sudden death had Eisenmenger syndrome. Right
      or left ventricular abnormalities were present in 15 of 21 patients with
      premorbid echocardiographic evaluation. A prior history of ventricular arrhythmia
      was available in only three patients. Sudden death is a significant cause of
      mortality in adults with congenital heart disease. Determination of risk factors
      will be an important aspect of the patient database under development by the CACH
      Network.

PMID- 9191510
TI  - Assessment of the cardiac patient for fitness to drive: 1996 update.

PMID- 9191511
TI  - PROTECT (Prospective Reinfarction Outcomes in the Thrombolytic Era Cardizem CD
      Trial): a randomized, double-blind clinical trial of diltiazem versus atenolol in
      secondary prophylaxis post non-Q wave myocardial infarction.
AB  - OBJECTIVE: To describe the rationale and design of the Prospective Reinfarction
      Outcomes in the Thrombolytic Era Cardizem CD Trial (PROTECT). DESIGN: A
      multicentre, randomized, double-blind, parallel-group comparison of once daily
      beta-therapy versus heart rate lowering calcium channel blocker therapy, in the
      reduction of one-year nonfatal reinfarction and cardiovascular death (combined
      primary end-point) initiated 24 to 96 h post non-Q wave myocardial infarction.
      SETTING: One hundred and twenty hospitals across Canada. PATIENTS: Over 7500
      women and men aged 21 years or older with enzyme-confirmed non-Q wave infarction
      and without significant left ventricular systolic dysfunction will be recruited
      over two years. INTERVENTIONS: Once daily beta-blocker therapy (oral atenolol, 50
      to 200 mg) versus once daily calcium channel blocker therapy (oral diltiazem 120
      to 360 mg) with follow-up for up to three years. CONCLUSIONS: The PROTECT will be
      the largest all-Canadian cardiovascular trial to date and will compare two
      commonly prescribed agents for secondary prophylaxis following non-Q wave
      infarction. The scientific question addressed by the PROTECT is of major public
      health importance and the results of the study will directly affect current
      clinical practice.

PMID- 9191512
TI  - A dose-response study of perindopril in hypertension: effects on blood pressure 6
      and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group.
AB  - OBJECTIVE: To examine the dose-response characteristics of perindopril at the
      time of its peak and trough antihypertensive effects, with the primary outcome
      measure being changes in diastolic blood pressure. DESIGN: After a four-week,
      single-blind placebo run-in, patients were randomly allocated to four doses of
      perindopril or placebo using a parallel group design. SETTING: Sixteen specialist
      centres in the United States. PATIENTS: Of 483 patients entered into the run-in
      phase, 293 were eligible for randomization to perindopril or placebo therapy,
      with 260 patients included in the final efficacy analysis. INTERVENTIONS:
      Eligible patients were randomized to 12 weeks of therapy with perindopril 2, 4, 8
      or 16 mg or placebo. MAIN RESULTS: At the final visit, all doses of perindopril
      significantly (P < 0.05) lowered diastolic blood pressure compared with placebo.
      The ratio of changes in placebo-corrected diastolic blood pressure at 24 versus 6
      h for perindopril 2, 4 and 8 mg was 1.0, 1.0 and 0.97, respectively. The maximum
      antihypertensive effect was seen with perindopril 8 mg, with the 16 mg dose
      providing no additional response. Changes in systolic and diastolic blood
      pressure were similar. CONCLUSIONS: Perindopril is most effective at doses of 4
      and 8 mg once daily, with similar reductions in diastolic blood pressure present
      at 6 and 24 h after dosing.

PMID- 9191513
TI  - Unusual accelerated progression of saccular aneurysms in an ectatic right
      coronary artery.
AB  - Localized aneurysmal dilation or ectasia of coronary arteries is a relatively
      uncommon angiographic finding, of which the pathophysiological mechanism remains
      speculative. The majority of patients diagnosed with this clinical entity usually
      present with angina pectoris. Furthermore, it is rare to find isolated ectasia or
      aneurysm dilation of the coronary arteries in patients with no prior history of
      coronary artery disease. The natural course is usually slowly progressive. This
      case demonstrates an unusual accelerated dilation of coronary saccular aneurysms,
      within a year of diagnosis, in a patient who presented with new onset congestive
      heart failure. Although the diagnosis was made with coronary angiography, both
      magnetic resonance imaging and transesophageal echocardiography were of critical
      diagnostic value to identify the size and extension of the aneurysms as well as
      the presence of intraluminal thrombi.

PMID- 9191514
TI  - Determining ejection fraction by Doppler echocardiography.

PMID- 9191515
TI  - Darwin's clinical relevance.

PMID- 9191516
TI  - 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future
      challenges.
AB  - BACKGROUND: Photodynamic therapy (PDT) for cancer patients has developed into an
      important new clinical treatment modality in the past 25-years. PDT involves
      administration of a tumor-localizing photosensitizer or photosensitizer prodrug
      (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and
      the subsequent activation of the photosensitizer by light. Although several
      photosensitizers other than ALA-derived protoprophyrin IX (PpIX) have been used
      in clinical PDT, ALA-based PDT has been the most active area of clinical PDT
      research during the past 5 years. Studies have shown that a higher accumulation
      of ALA-derived PpIX in rapidly proliferating cells may provide a biologic
      rationale for clinical use of ALA-based PDT and diagnosis. However, no review
      updating the clinical data has appeared so far. METHODS: A review of recently
      published data on clinical ALA-based PDT and diagnosis was conducted. RESULTS:
      Several individual studies in which patients with primary nonmelanoma cutaneous
      tumors received topical ALA-based PDT have reported promising results, including
      outstanding cosmetic results. However, the modality with present protocols does
      not in general, appear to be superior to conventional therapies with respect to
      initial complete response rates and long term recurrence rates, particularly in
      the treatment of nodular skin tumors. Topical ALA-PDT does have the following
      advantages over conventional treatments: it is noninvasive; it produces excellent
      cosmetic results; it is well tolerated by patients; it can be used to treat
      multiple superficial lesions in short treatment sessions; it can be applied to
      patients who refuse surgery or have pacemakers and bleeding tendency; it can be
      used to treat lesions in specific locations, such as the oral mucosa or the
      genital area; it can be used as a palliative treatment; and it can be applied
      repeatedly without cumulative toxicity. Topical ALA-PDT also has potential as a
      treatment for nonneoplastic skin diseases. Systemic administration of ALA does
      not seem to be severely toxic, but the advantage of using this approach for PDT
      of superficial lesions of internal hollow organs is still uncertain. The ALA
      derived porphyrin fluorescence technique would be useful in the diagnosis of
      superficial lesions of internal hollow organs. CONCLUSIONS: Promising results of
      ALA-based clinical PDT and diagnosis have been obtained. The modality has
      advantages over conventional treatments. However, some improvements need to be
      made, such as optimization of parameters of ALA-based PDT and diagnosis;
      increased tumor selectivity of ALA-derived PpIX; better understanding of light
      distribution in tissue: improvement of light dosimetry procedure; and development
      of simpler, cheaper, and more efficient light delivery systems.

PMID- 9191517
TI  - The value of DNA flow cytometry in predicting the development of lymph node
      metastasis and survival in patients with locally recurrent oral squamous cell
      carcinoma.
AB  - BACKGROUND: DNA flow cytometry studies of squamous cell carcinoma of the head and
      neck have shown that patients with diploid tumors have favorable prognoses,
      whereas the outcomes of those with, aneuploid tumors are poor. This study was
      conducted to examine the importance of DNA ploidy in patients with locally
      recurrent oral carcinoma. METHODS: DNA flow cytometry was performed on 93 primary
      oral carcinomas and their subsequent recurrences. RESULTS: Eight patients with
      diploidy of both the primary tumor and the recurrence never developed lymph node
      metastasis. The 5-year overall survival rate of this group was 87%. For 80
      aneuploid primary carcinomas, recurrences developed that were also aneuploid.
      Only 31% of these patients were 5-year survivors (P < 0.001). Lymph node
      metastasis at presentation was found in 55% of this group, whereas 13% of
      initially lymph node negative patients presented with regional disease at second
      surgery. Five of 13 diploid primary tumors recurred with aneuploid cell lines.
      Three of these five patients died, two with regional metastasis. The 5-year
      survival rate of patients with aneuploid recurrences who were never afflicted
      with lymph node involvement (41%) was better (P < 0.05) than the 5-year survival
      rate of those with metastasis at presentation or at second surgery (26%).
      CONCLUSIONS: The excellent prognosis of patients with diploid primary tumors can
      be reestablished by treating local recurrences with radical surgery, if the
      surgery is performed before aneuploid cell lines have emerged. It appears that
      aneuploid tumor cell lines acquire unique properties that make them capable of
      invasion and metastasis.

PMID- 9191518
TI  - Detection of numeric abnormalities of chromosome 17 and p53 deletions by
      fluorescence in situ hybridization in pleomorphic adenomas and carcinomas in
      pleomorphic adenoma. Correlation with p53 expression.
AB  - BACKGROUND: A fluorescence in situ hybridization (FISH) technique using specific
      DNA probes allows for the detection of chromosomal aberrations and gene deletions
      and gains, even in interphase nuclei in human solid tumors. A high frequency of
      aberrations of chromosome 17 and mutation of the p53 gene have been reported in
      some human tumors. The correlation of p53 expression with abnormalities of
      chromosome 17 and p53 gene deletion in salivary gland tumors has not yet been
      investigated. METHODS: The authors analyzed the numeric aberrations of chromosome
      17 and p53 gene deletions in 11 paraffin embedded pleomorphic adenomas (PA) and 9
      carcinomas in pleomorphic adenoma (CIPA), using FISH techniques. The centromere
      specific DNA probe for chromosome 17 and p53 cosmid DNA probe was used. The
      aberrations of chromosome 17 and p53 deletion were correlated with
      immunohistochemical detection of p53 protein. RESULTS: Monosomy 17 was detected
      in 30.8% of CIPA cells and 29.6% of PA cells, and polysomy 17 was detected in
      19.6% of CIPA cells and 9.6% of PA cells. p53 protein expression was observed in
      6 of 9 CIPA specimens (66.7%) and 2 of 75 PA specimens (2.7%). Deletion of the
      p53 gene was frequent in p53 protein positive specimens. A statistically
      significant correlation existed between p53 protein expression and polysomy 17 (P
      = 0.0417). CONCLUSIONS: It was observed that loss of chromosome 17 may occur in
      PA before its transformation to carcinoma. p53 expression was frequently
      associated with deletion of the p53 gene as detected by FISH. Polysomy 17 was
      more frequent in CIPA than PA and was associated with mutation of p53.

PMID- 9191519
TI  - The prognostic significance of intratumoral natural killer cells in patients with
      colorectal carcinoma.
AB  - BACKGROUND: Natural killer (NK) cells have a spontaneous cytotoxic capacity
      against tumor cells. These cells represent a small proportion of human colon
      carcinoma-infiltrating lymphocytes. Their prognostic significance in these tumors
      has yet to be determined. METHODS: One hundred and fifty-seven patients who each
      had a colectomy for large bowel adenocarcinoma were studied. No patient received
      adjuvant therapy. Immunohistochemical stains were performed for NK cells using
      the monoclonal antibody CD57. The number of NK cells was counted using a MICRON
      image analyzer. The total area studied for each tumor was 1 cm2. In this area, 50
      intratumoral fields of 0.173 mm2 were selected. The degree of NK infiltration was
      classified as little (< 50 NK cells), moderate (50-150 NK cells), and extensive
      (> 150 NK cells). The Kaplan-Meier method was used to obtain survival figures.
      Multivariate analyses were performed using the Cox regression model. RESULTS: At
      5 years, patients with little and moderate NK infiltration showed significantly
      shorter survival rates (overall and disease free survival) than those with
      extensive infiltration (P < 0.01). Three significant factors affecting survival
      were selected in a stepwise fashion in increasing order as follows: TNM stage, NK
      infiltration, and lymphocytic infiltration. Patients with TNM Stage III disease
      and extensive NK infiltration showed significantly longer survival rates than
      those with little or moderate infiltration (P < 0.001). In these patients,
      multivariate analysis using the Cox regression model identified two significant
      variables: number of involved lymph nodes and NK cells infiltration. CONCLUSIONS:
      In patients with colorectal carcinoma, an extensive intratumoral infiltration of
      NK cells is associated with a favorable tumor outcome. Intratumoral infiltration
      of NK cells can be used as a variable with prognostic value, especially in
      patients with TNM Stage III disease.

PMID- 9191520
TI  - The impact of treatment factors on local control in T2-T3 anal carcinomas treated
      by radiotherapy with or without chemotherapy.
AB  - BACKGROUND: This study was conducted to investigate the influence of therapeutic
      parameters on local control (LC) in the sphincter-conserving treatment of T2-T3
      anal carcinoma. METHODS: From 1976 to 1993, 137 patients with anal carcinoma
      classified as T2 (85 patients) or T3 (52 patients) were treated curatively by
      radiotherapy (RT) alone (54 patients) or by concomitant chemotherapy and RT (83
      patients). RT was delivered in two sequences, with a median gap of 46 days
      between the sequences. The first sequence was delivered at a median dose of 39.6
      gray (Gy) using megavoltage photon beams. Boost treatment consisted of either
      192Ir implantation or external beam RT (median dose, 20 Gy). Chemotherapy started
      on Day 1 and generally consisted of 1 cycle of mitomycin C (10 mg/m2) and a 5-day
      infusion of 5-fluorouracil (600-800 mg/m2/day). For surviving patients, median
      follow-up was 83 months. Univariate and multivariate analyses were performed to
      determine therapeutic parameters affecting LC after adjustment for clinical
      factors. RESULTS: The 5-year actuarial LC was 76%. Factors associated with poorer
      LC (univariate) were as follows: age < 66 years (LC was 67% with the factor vs.
      85% without), male gender (65% vs. 81%), tumor extent > 1/3 canal circumference
      (67% vs. 90%), lymph node involvement (64% vs. 81%), use of external beam boost
      (62% vs. 79%), and overall treatment time (OTT) > or = 75 days (69% vs. 85%). In
      multivariate analysis, no therapeutic parameters remained significant when
      adjusted for significant clinical factors, although OTT was of borderline
      significance (P = 0.09). CONCLUSIONS: The results of this multivariate analysis
      suggest that therapeutic factors have a less marked effect on LC compared with
      clinical parameters; the only factor that appeared to have some effect was OTT.
      Efforts to improve LC in patients with poor prognoses should concentrate on
      optimizing OTT and the chemotherapeutic aspects of treatment (in other words,
      attempts should be made to provide more effective agents and optimize
      scheduling).

PMID- 9191521
TI  - Overexpression of resistance-related proteins (metallothioneins, glutathione-S
      transferase pi, heat shock protein 27, and lung resistance-related protein) in
      osteosarcoma. Relationship with poor prognosis.
AB  - BACKGROUND: The prognosis for patients with osteosarcoma has improved over the
      past 20 years, mainly due to developments in chemotherapy. Some proteins have
      been reported to show drug resistance. Theoretically, overexpression of some of
      these proteins makes treatment difficult, leading to poorer outcome. METHODS:
      Specimens taken from conventional osteosarcomas of the extremity bones from 60
      patients younger than 30 years were used. In all cases, preoperative oncostatic
      chemotherapy was undertaken after biopsy. If available, biopsy specimens were
      also used for sequential comparison. Among resistance-related proteins,
      expression of metallothioneins (MTs), glutathione-S-transferase pi (GST pi), heat
      shock protein 27 (Hsp27), and lung resistance-related protein (LRP) was evaluated
      immunohistochemically in paraffin sections. The log rank test was used for
      univariate analysis and the Cox regression model for multivariate analysis.
      RESULTS: At biopsy, only overexpression of Hsp27 was associated with poor
      prognosis. At surgery, a relationship was observed between poor prognosis and
      overexpression of GST pi, Hsp27, and LRP. Groups overexpressing one protein
      tended to overexpress another. Overexpression of these proteins in surgical
      specimens also correlated with histologic response to preoperative chemotherapy
      and clinical stage. In multivariate analysis, Hsp27 overexpression at biopsy was
      an independent prognostic factor. CONCLUSIONS: Inherent overexpression of Hsp27
      is independently related to poor outcome in osteosarcoma patients. Overexpression
      of GST pi, Hsp27, and LRP at surgery might be associated with failure of
      preoperative chemotherapy. Control of the expression of these proteins may
      improve the outcome for patients with osteosarcoma.

PMID- 9191522
TI  - Prolonged survival of 2 years or longer for patients with disseminated melanoma.
      An analysis of related prognostic factors.
AB  - BACKGROUND: Once melanoma has metastasized to distant sites, the prognosis is
      usually poor, showing an overall median survival of 6-8 months. Long term
      survival is extremely rare, and there is still controversy concerning the
      prognostic significance of therapeutic modalities. The aim of the current study
      was to identify important prognostic factors associated with Stage IV melanoma.
      METHODS: The current study was based on data for 3258 melanoma patients, for whom
      clinical, pathologic, and long term follow-up information was recorded during the
      period 1976-1996 at the Eberhard-Karls-University in Tuebingen. Germany. The
      attainment of 2 years' or longer survival time by patients with disseminated
      melanoma was addressed, and a multivariate analysis of related prognostic factors
      was performed by logistic regression. RESULTS: Four hundred forty-two patients
      (13.6%) developed distant metastasis. The median survival time was 7 months, and
      the 2-year, 5-year, and 10-year survival rates were 11.9%, 6.7%, and 4.7%,
      respectively. Forty-five patients had prolonged survival of 2 years or longer.
      Significantly more females belonged to the group of long term survivors (P =
      0.0186). Of the modalities of therapy given, only surgery was associated with
      prolonged survival (P < 0.0001). Primary metastasis to the skin (P = 0.006), the
      brain (P = 0.015), more than a single metastatic site (P = 0.002), and Karnofsky
      performance status of less than 80 (P = 0.0035) were significantly related to
      short term survival. In addition, subsequent development of two or more new
      metastatic sites was also associated with short term survival (P = 0.0025).
      CONCLUSIONS: In the current analysis, prolonged survival of 2 years or longer for
      patients with disseminated melanoma was shown to depend on gender, site of
      primary metastasis, number of metastatic sites, and Karnofsky performance status.
      Of the modalities of therapy given, only surgery significantly influenced
      survival. However, in a small percentage of patients, long term complete
      remission was achieved with chemotherapy alone or in combination with surgery,
      suggesting that such regimens might be curative in selected cases.

PMID- 9191523
TI  - Postsurgical adjuvant therapy for melanoma. Evaluation of a 3-year randomized
      trial with recombinant interferon-alpha after 3 and 5 years of follow-up.
AB  - BACKGROUND: Early surgical intervention is still the most successful therapy for
      patients with melanoma. The results obtained with medical therapies are still
      quite disappointing, with better results observed in soft tissue and lymph node
      metastasis. There currently is no standardized adjuvant therapy for primary
      melanoma. On the basis of the activity demonstrated in vitro against melanoma
      cell lines and the results obtained in many clinical trials in patients with
      advanced melanoma, the authors chose to study the use of recombinant interferon
      alpha (IFN-alpha) as adjuvant therapy for patients with Stage I and Stage II
      melanoma. METHODS: A randomized multicenter trial based on the use of recombinant
      IFN-alpha-2b for 3 years at the dose of 3 MU given intramuscularly 3 times a week
      for a period of 6 months with a 1-month interval between cycles was conducted in
      Stage I and Stage II melanoma patients (using the American Joint Committee on
      Cancer classification). The efficacy of this treatment was evaluated calculating
      the incidence of recurrence after 3 and 5 years. RESULTS: Results were collected
      at the end of the treatment period and after 5 years of follow-up for a smaller
      number of patients. Statistical evaluation showed a significant difference
      between treated patients and untreated controls with regard to progression of the
      disease. In particular, IFN-alpha appears to be more effective in patients with
      worse prognosis lesions. CONCLUSIONS: IFN-alpha appears to be effective as
      adjuvant therapy for high risk melanoma patients and the risk/benefit ratio
      appears to be very favorable. The authors' next goal is to separate those
      patients who might benefit from adjuvant therapy from those who are cured after
      the surgical intervention only.

PMID- 9191524
TI  - Ultra-late recurrence (15 years or longer) of cutaneous melanoma.
AB  - BACKGROUND: Melanoma can remain clinically quiescent for decades before regional
      or distant recurrence appears. This protracted disease free interval challenges
      the concept of a "cure" for melanoma. METHODS: To understand this prolonged
      dormancy better, the authors retrospectively studied patients who developed
      recurrent melanoma 15 years or longer after their initial diagnosis ("ultra-late"
      recurrence). These cases were identified from 2766 melanoma diagnoses available
      in the Cancer Registry at the Massachusetts General Hospital (MGH). Histologic
      features of the primary lesion were also included when possible. RESULTS: Twenty
      cases were retrieved from the MGH database. There were equal numbers of women and
      men, although women were younger at the time of initial diagnosis (mean age of
      women: 29.8 years vs. 43.0 years for men). No patients had more than one primary
      cutaneous melanoma. The trunk was the most common primary site (35%), although
      there was no predominant anatomic localization. The average disease free interval
      was 17.3 years for women, 20.0 years for men, 18.1 years for patients with
      regional recurrence, and 19.0 years for patients with distant metastases. Distant
      recurrence was the most common type of recurrence (50% of women and 60% of men).
      The estimated probability of survival (5 years after recurrence) was 0.8 for
      regional disease and 0.2 for distant disease. With the available histologic
      records, it appears that almost all tumors were Clark Level III or IV with
      thicknesses ranging from 0.8-2.3 mm. In contrast to the published cases, this
      study did not find that women with lower extremity melanomas were at higher risk
      for developing ultra-late recurrence. CONCLUSIONS: Ultra-late recurrence of
      melanoma, although uncommon, can occur in any patient without identifiable risk
      factors. Because many prognostically favorable melanomas (thin melanomas on
      extremities) can recur after prolonged disease free intervals, the possibility of
      delayed recurrence remains and must be kept in mind.

PMID- 9191525
TI  - Flow cytometric DNA content analysis of 185 soft tissue neoplasms indicates that
      S-phase fraction is a prognostic factor for sarcomas. French Federation of Cancer
      Centers (FNCLCC) Sarcoma Group.
AB  - BACKGROUND: The authors determined the flow cytometric (FCM) DNA characteristics
      of 53 benign tumors and 132 malignant (71 primary, 61 recurrent) soft tissue
      sarcomas to investigate their heterogeneity and to evaluate the prognostic values
      of DNA ploidy status and S-phase fraction (SPF). METHODS: One to 11 frozen
      samples were collected from 185 tumors at 10 participating centers of the French
      Federation of Cancer Centers (FNCLCC). All FCM analyses were performed in the
      same laboratory. Histologic diagnoses were collegially reviewed, and grade was
      assessed by the pathologists of the FNCLCC Sarcoma Group. Relationships between
      FCM, clinical, and pathologic data were investigated using univariate and
      multivariate analyses for risks of mortality and metastasis. RESULTS: All except
      2 of the 53 benign lesions were DNA diploid. One schwannoma and one desmoid tumor
      exhibited small abnormal DNA peaks. SPF was low in all benign lesions. One-third
      of the sarcomas were DNA diploid, whereas two-thirds were DNA aneuploid.
      Relationships were found between aneuploidy and mitotic count, grade, and
      histologic subtype of malignant fibrous histiocytoma. DNA ploidy status did not
      influence the clinical outcome. Multiple sampling performed in 32 sarcomas showed
      both diploid and aneuploid samples in 6 tumors. Heterogeneity was related to
      tumor size. SPF evaluated in 85 sarcomas was related to DNA ploidy status,
      mitotic count, and grade. SPF > or = 4% was significantly associated with a low
      overall survival rate. In a multivariate analysis performed for the whole group
      of 132 patients, the single factors with independent prognostic value for patient
      mortality were disease free status after the treatment course (P < 0.0001) and
      SPF (P = 0.03). In the subgroup of patients who were initially free of metastases
      and free of tumor after the treatment course, SPF remained the only factor that
      significantly influenced the overall survival rate (P = 0.021). CONCLUSIONS:
      Despite its high failure rate, SPF is an independent factor in the prognosis of
      soft tissue sarcoma and should be considered when patients with a high mortality
      risk need to be selected for adjuvant chemotherapy.

PMID- 9191526
TI  - Multidisciplinary breast cancer clinics. Do they work?
AB  - BACKGROUND: In an attempt to improve the care they provide for their patients
      with breast cancer, the authors' institution developed a multidisciplinary breast
      cancer clinic (MDBCC) to offer "one-stop shopping" consultation and support for
      newly diagnosed breast cancer patients. METHODS: One hundred sixty-two patients,
      the control group for this study, were evaluated at Henry Ford Hospital during
      the year prior to the opening of the MDBCC. These patients, who were referred in
      the traditional sequential consultation manner, were compared with the first 177
      patients seen during the first year of the clinic's operation. Retrospective
      chart reviews were conducted to assess treatment timeliness, and anonymous
      questionnaires were used to assess patient satisfaction. RESULTS: The authors
      found that the MDBCC increased patient satisfaction by encouraging involvement of
      patients' families and friends and by helping patients make treatment decisions
      (P < 0.001). The time between diagnosis and the initiation of treatment was also
      significantly decreased (42.2 days vs. 29.6 days; P < 0.0008). CONCLUSIONS:
      Although planning and operating a multidisciplinary clinic is not a new venture,
      to the best of the authors' knowledge, they have provided the first report
      demonstrating the benefits described above.

PMID- 9191527
TI  - Overexpression of eukaryotic initiation factor 4E (eIF4E) in breast carcinoma.
AB  - BACKGROUND: Eukaryotic initiation factor 4E (eIF-4E) is a 25-kilodalton
      phosphoprotein that binds specifically to mRNA as the initial step for mRNA
      translation. An elevated level of eIF4E has been associated with the up
      regulation of various protooncogene products. Transfection of cell lines by viral
      vectors with eIF4E overexpression has resulted in malignant transformation. The
      objective in this study was twofold: to examine benign and malignant breast
      specimens for eIF4E expression, and to determine whether eIF4E overexpression may
      have prognostic potential. METHODS: Western blot analysis was performed on benign
      and malignant breast specimens using anti-eIF4E rabbit antiserum. Quantification
      was accomplished by developing blots with nitroblue tetrazolium and 5-bromo-4
      chloro-3-indolyl phosphate and densitometry. Confirmation of eIF4E overexpression
      at the cellular level was performed using immunohistologic staining in situ.
      RESULTS: The authors examined 112 breast specimens for eIF4E protein expression.
      Of the 52 benign breast specimens examined, none showed eIF4E overexpression. All
      12 ductal carcinoma in situ specimens were found to overexpress eIF4E in the
      intermediate range (mean elevation: 2.5-fold). Of the 48 breast carcinoma
      specimens examined, all had eIF4E elevation at levels of 3-30-fold (mean: 10.5 +/
      0.9-fold). Charts from 39 patients with Stage I, II, and III breast carcinoma
      were reviewed. In ten patients with eIF4E overexpression of < sevenfold, there
      was no recurrence or death from breast carcinoma. In the 29 breast carcinoma
      patients with > or = 7-fold eIF4E overexpression, 9 patients had breast carcinoma
      recurrences and 5 had died from disease at last follow-up. The median follow-up
      in this study was 34.5 months. CONCLUSIONS: Overexpression of eIF4E was observed
      in malignant breast specimens but not in normal or benign breast tissues. In
      patients with breast carcinoma, the group with high eIF4E overexpression (> or =
      7-fold) experienced a worse clinical outcome (higher recurrences and death)
      compared with the group with low eIF4E overexpression (< 7-fold).

PMID- 9191529
TI  - Perineal talc exposure and risk of ovarian carcinoma.
AB  - BACKGROUND: Clinical and epidemiologic studies have indicated the possible
      existence of an association between ovarian carcinoma and talcum powder use. Talc
      particles have been detected in histologic sections of ovarian carcinomas. It has
      also been demonstrated that inert particles travel from the perineum to the
      ovaries. Results from epidemiologic investigations have varied, from risks
      increased by twofold to no significant risk detected. METHODS: A total of 450
      patients with borderline and invasive ovarian carcinoma and 564 population
      controls in metropolitan Toronto and nearby areas of southern Ontario, Canada,
      were identified. These subjects were interviewed about their reproductive and
      menstrual histories as well as their exposure to dusting powders. Continuous
      unconditional logistic regression methods were used for analysis. RESULTS:
      Exposure to talc, via sanitary napkins, direct application to the perineum, or
      both, was significantly associated with risk of ovarian carcinoma (odds ratio
      [OR] 1.42, 95% confidence interval [CI] 1.08-1.86). A borderline-significant
      association was detected between duration of talc exposure and risk (OR 1.09, 95%
      CI 0.98-1.21, per 10 years of exposure). No significant association was found
      between frequency of exposure and risk. In comparing invasive and borderline
      carcinomas, risk remained elevated for both carcinoma types. Only risk for
      invasive carcinoma was statistically significant. CONCLUSIONS: This investigation
      supports previous contentions that exposure to talc may increase risk of ovarian
      carcinoma. Questionable trends in duration and frequency of exposure suggest that
      further studies may be needed to clarify the role of talc in the etiology of this
      disease.

PMID- 9191528
TI  - A phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in the
      treatment of metastatic carcinoma of the uterine cervix.
AB  - BACKGROUND: Patients with metastatic carcinoma of the uterine cervix have limited
      survival. Thus, new chemotherapeutic agents and combinations are needed to
      improve patient outcome. METHODS: Twenty-seven patients with Stage IV primary or
      recurrent carcinoma of the uterine cervix were assigned to chemotherapy treatment
      at 4-week intervals with methotrexate, vinblastine, doxorubicin, and cisplatin
      (MVAC). The treatment was comprised of methotrexate, 30 mg/m2 administered
      intravenously (i.v.) on Days 1, 15, and 22; vinblastine, 3 mg/m2 i.v. on Days 2,
      15, and 22; doxorubicin, 30 mg/m2 i.v. on Day 2; and cisplatin, 70 mg/m2 i.v. on
      Day 2. Granulocyte-colony stimulating factor (G-CSF) was given subcutaneously on
      Days 6-10 at a dose of 5 micrograms/kg. RESULTS: After a median of 4 cycles (a
      maximum of 6 in responders), the authors observed objective responses in 14
      patients (52%), including 3 complete responses (11%) and 11 partial responses
      (41%). Median overall survival was 11 months (range, 4-15+ months), and median
      progression free survival of the responders was 8 months (range, 6-15+ months).
      Toxicity was acceptable and included neutropenia, alopecia, vomiting, and
      stomatitis. CONCLUSIONS: MVAC is an active regimen in the treatment of patients
      with advanced or recurrent carcinoma of the uterine cervix. It produced responses
      in one-half of the patients in this study, and it can be administered on an
      outpatient basis. The addition of G-CSF appears to reduce hematologic toxicity.

PMID- 9191530
TI  - Detection of circulating prostate carcinoma cells via an enhanced reverse
      transcriptase-polymerase chain reaction assay in patients with early stage
      prostate carcinoma. Independence from other pretreatment characteristics.
AB  - BACKGROUND: Circulating prostate cells can be detected in the venous blood of
      patients with clinically localized prostate carcinoma by applying reverse
      transcriptase-polymerase chain reaction (RT-PCR) techniques using primers
      specific for the prostate specific antigen (PSA) gene. This study evaluates
      whether the detection of circulating cells correlates with established prognostic
      factors, treatment, and pathologic stage. METHODS: Two hundred and twenty-seven
      patients with clinically localized adenocarcinoma of the prostate had an RT-PCR
      assay performed as part of their staging evaluation. No treatment decisions were
      made on the basis of the RT-PCR results. Of these, 156 patients were treated with
      radical prostatectomy (RP) and 71 with radical external beam radiotherapy (EBRT).
      Forty-eight patients were treated with hormonal therapy prior to RP (n = 39) or
      EBRT (n = 9). The prognostic factors analyzed for their relationship to RT-PCR
      were clinical stage, pretreatment serum PSA levels, Gleason score of the biopsy
      specimen, and Gleason score of the surgical specimen. An analysis of the
      relationship between treatment and RT-PCR results was also performed.
      Multivariate logistic regression analysis of predictors of RT-PCR positivity was
      performed as well. In addition, univariate and multivariate analyses of
      predictors of pathologic stage, including RT-PCR, were performed. RESULTS: Sixty
      one patients (26.9%) had a positive RT-PCR assay. There was no relationship
      between clinical stage, pretreatment PSA, biopsy Gleason score, or surgical
      Gleason score and RT-PCR positivity. In univariate analysis, patients treated
      with RP had a higher rate of RT-PCR positivity than patients treated with EBRT (P
      = 0.054). However, in multivariate logistic regression analysis no factor,
      including treatment with RP, was a significant predictor of RT-PCR positivity. RT
      PCR and pretreatment PSA predicted pathologic stage in univariate and
      multivariate analyses (P < 0.0001 and P = 0.002, respectively). CONCLUSIONS: The
      detection of circulating prostate cells using RT-PCR occurs in approximately 25%
      of early stage prostate carcinoma patients and is independent of other
      established prognostic factors. In addition, a positive RT-PCR assay is a strong
      predictor of pathologic upstaging in patients with clinically organ-confined
      disease.

PMID- 9191531
TI  - Will primary central nervous system lymphoma be the most frequent brain tumor
      diagnosed in the year 2000?
AB  - BACKGROUND: There has been a dramatic increase in the diagnosis of primary
      lymphoma of the brain during the past decade, prompting speculation that it may
      become the most frequently diagnosed tumor of the central nervous system by the
      year 2000. The current analysis drew from the updated Surveillance, Epidemiology,
      and End Results (SEER) database to establish projections for the incidence of
      brain lymphoma. The study also attempted to determine whether increased incidence
      rates are attributable to the increasing incidence of acquired immunodeficiency
      syndrome (AIDS) and whether there is gender or age dependence. METHODS: Primary
      brain lymphoma case data and population census data for calculating incidence
      rates for the period 1973-1992 were obtained from the SEER program. In an attempt
      to determine the contribution of AIDS to the increasing incidence of the disease,
      separate analyses were performed with and without the inclusion of never married
      men (a high risk group for the development of AIDS). Separate analyses were also
      performed within the San Francisco SEER registry because a higher incidence of
      AIDS-related cancers has been documented in this geographic region. Finally, a
      piece-wise linear model (using one regression line until 1982 and another
      regression line from 1982 onward) was used to predict incidence rates for the
      year 2000. RESULTS: During the period of study, the incidence rates of brain
      lymphoma increased more than 10-fold, from 2.5 cases per 10 million population in
      1973 to 30 in 1991-1992 (chi-square trend, 17.76: P < 0.0001). These increased
      incidence rates were independent of age and gender. The incidence rates of
      primary brain lymphoma did not differ significantly when comparing the San
      Francisco registry with the remainder of the SEER database for any comparison
      that excluded never married males. However, when the analysis included never
      married males, a statistically significantly higher incidence rate of primary
      central nervous system lymphoma was observed among San Franciscans compared with
      age-matched controls from the remainder of the SEER database. In the year 2000,
      the projected incidence rate of brain lymphoma would reach 51.1 per 10 million
      population and 118.2 per 10 million population, with never married men excluded
      and included, respectively. These incidence rates would still fall below the
      corresponding projections for glioma and glioblastoma multiforme. CONCLUSIONS:
      There continues to be a significantly increasing incidence of brain lymphoma that
      is independent of age and gender. Indirect evidence implicates the AIDS epidemic
      as a contributor to this trend. Although the rate of increase in the incidence of
      non-Hodgkin's lymphoma of the brain is higher than for peripheral non-Hodgkin's
      lymphoma and other glial tumors, brain lymphoma is not projected to surpass glial
      tumors as the most frequently diagnosed intracranial malignancy by the year 2000.

PMID- 9191532
TI  - A comparison of different staging systems predictability of patient outcome.
      Thyroid carcinoma as an example.
AB  - BACKGROUND: There is no consensus regarding the comparison of staging
      classifications. Recently, numerous staging classifications for thyroid carcinoma
      have been described. This study was performed to evaluate the relative
      discriminating ability of these different staging systems. METHODS: A literature
      review was conducted to identify the available staging classifications used for
      thyroid carcinoma. To compare the various staging classifications, cause specific
      survival data from a retrospective review of 382 patients with papillary and
      follicular thyroid carcinoma treated at Princess Margaret Hospital were applied
      to the various staging classifications. The ability of these classifications to
      distinguish the stage groupings were compared in the following ways: 1)
      tabulating the numbers of patients within each stage group; 2) collapsing stage
      groupings into high and low risk groups and calculating mortality rates at 10 and
      15 years; 3) summing observed deviations at 5, 10, and 15 years; and 4)
      calculating the proportion of variance explained (PVE) for each staging
      classification, using each classification separately as a prognostic factor in a
      Cox regression model. RESULTS: The application of the PVE model, the only method
      of the four that used statistical inference, showed no statistically significant
      superiority of any system over the TNM classification of the American Joint
      Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in
      their ability to discriminate stage groupings. CONCLUSIONS: Because the TNM
      classification of the AJCC and UICC is universally available and widely accepted
      for other disease sites, the authors recommend it for all reports of the
      treatment and outcome of patients with thyroid carcinoma. Individual research
      groups also may use an alternative, validated classification to report results,
      provided that the outcomes are also reported using the TNM classification to
      facilitate comparison between different centers.

PMID- 9191533
TI  - Association between human cancer and two polymorphisms occurring together in the
      p21Waf1/Cip1 cyclin-dependent kinase inhibitor gene.
AB  - BACKGROUND: The cyclin-dependent kinase inhibitor gene p21Waf1/Cip1 plays a role
      in signaling cellular growth arrest. In response to DNA damage, p21 is induced by
      the p53 gene, thereby playing a direct role in mediating p53-induced G1 arrest.
      Alterations in this gene may adversely affect regulation of cellular
      proliferation and increase susceptibility for cancer. Two polymorphisms have
      previously been characterized in the p21 gene: a C-->A transversion at codon 31
      (ser-->arg) and a C-->T transition 20 nucleotides downstream from the 3' end of
      exon 3. METHODS: The codon 31 polymorphism in exon 2 of the p21 gene was
      identified by restriction digestion (Alw26I) of products amplified by polymerase
      chain reaction (PCR). The polymorphism downstream from exon 3 of the p21 gene was
      identified by single strand conformation polymorphism (SSCP) analysis of PCR
      amplified products and was confirmed by PstI enzyme restriction digestion. DNA
      variant alleles were confirmed by direct DNA sequencing. The entire coding region
      and the promoter region (p53 binding domain) of the p21 gene were screened for
      mutations by SSCP analysis or DNA sequencing. RESULTS: The two polymorphisms were
      found in 18 of 96 tumor samples lacking p53 alterations (18.8%). Nine of 54
      prostate adenocarcinoma samples (16.7%) contained both p21 variants, whereas 9 of
      42 squamous cell carcinomas of the head and neck (21.4%) displayed both
      polymorphisms. Of the 110 controls examined, 10 (9.1%) had both alterations. Both
      p21 polymorphisms occurred together in all samples examined and there was no
      indication of mutation in the coding region of the p21 gene or in the p53 binding
      domain of the promoter region. CONCLUSIONS: These data suggest that p21 gene
      variants may play a role in increased susceptibility for the development of some
      types of cancer. In the current study, the authors demonstrated that the
      occurrence of these two polymorphisms is increased in prostate adenocarcinoma and
      squamous cell carcinoma of the head and neck. The polymorphic sites may be
      directly responsible for this apparent increased susceptibility or they may be
      linked to regulatory region alterations.

PMID- 9191534
TI  - Differential expression of p53, c-kit, and CD34 in prepubertal and postpubertal
      testicular germ cell tumors.
AB  - BACKGROUND: The origin of testicular germ cell tumors (TGCTs) in children is
      poorly understood. There are clear differences between tumors in young children
      and those in adolescents and adults, which may suggest that they follow different
      pathways of tumorigenesis. METHODS: Tissue sections from 25 TGCTs (15 from
      patients age 4 years or younger and 10 from adolescents or adults) were stained
      immunohistochemically with anti-p53 (DO-1), CD34, and c-kit proto-oncogene
      protein product. RESULTS: CD34 expression was noted only in 5 prepubertal tumors.
      Expression of c-kit was observed in 9 of the 15 prepubertal tumors versus 2 of
      the 10 postpubertal cases. The intensity of expression was equal to that of the
      adjacent normal tubules in the prepubertal tumors, whereas the intensity was less
      in the postpubertal tumors. Expression of p53 was strong in 8 of the 10 tumors in
      adolescents or adults, with a 40-70% positivity, whereas only 6 of 15 prepubertal
      tumors expressed p53, with < 10% positivity. CONCLUSIONS: CD34 expression in
      tumors in the group of young children suggests a possible link to teratomas and
      further provides insight into the fundamental differences between this group and
      the adolescent/adult group. The expression of c-kit and p53 provides further
      evidence that c-kit/SCF signaling and p53 play potentially different roles in the
      initiation and progression of these tumors. Future studies will be required to
      clarify this issue.

PMID- 9191535
TI  - Venoocclusive disease of the liver after chemotherapy with vincristine,
      actinomycin D, and cyclophosphamide for the treatment of rhabdomyosarcoma. A
      report of the Intergroup Rhabdomyosarcoma Study Group. Childrens Cancer Group,
      the Pediatric Oncology Group, and the Pediatric Intergroup Statistical Center.
AB  - BACKGROUND: Venoocclusive disease (VOD) of the liver is a common complication
      after allogenic and autologous bone marrow transplantation for malignant disease.
      The authors report the unusual and unexpected complication of VOD of the liver
      occurring in children with rhabdomyosarcoma who were receiving vincristine,
      actinomycin D, and cyclophosphamide (VAC) according to the chemotherapy regimens
      of the Intergroup Rhabdomyosarcoma Study (IRS) IV. METHODS: The authors evaluated
      821 patients with newly diagnosed rhabdomyosarcoma receiving treatment according
      to IRS IV who were considered at risk for VOD. RESULTS: Ten patients developed
      VOD of the liver for an overall incidence of 1.2%. VOD was found only after the
      administration of VAC chemotherapy. The highest incidence of VOD was observed
      among patients who had previously received vincristine and melphalan (Regimen
      48). None of the patients receiving the chemotherapy regimen of vincristine and
      actinomycin D (Regimen 44) developed VOD. CONCLUSIONS: Patients receiving VAC
      containing regimens on the IRS IV were found to be at risk for VOD. The VAC
      combination was used extensively in previous IRS studies (I, II, and III) and VOD
      was not reported during these studies, strongly suggesting that the escalation of
      the cyclophosphamide dose to 2.2 g/m2 (with the vincristine and actinomycin D
      doses and schedule remaining unchanged) triggered the development of VOD. The
      contributing role of previous therapy or events is unknown. At last follow-up,
      none of the nine surviving patients had developed recurrent VOD on continuation
      of chemotherapy.

PMID- 9191536
TI  - Brain metastases in children with melanoma.
AB  - BACKGROUND: Brain metastases complicate the course of malignant melanoma in at
      least 20% of adult cases. These events are commonly preceded by metastases to
      other sites. Due to the rarity of malignant melanoma in children, little is known
      about the incidence, clinical features, and outcome of children with melanoma who
      develop brain metastases. METHODS: The authors reviewed the records of 44
      children with malignant melanoma treated at St. Jude Children's Research Hospital
      over a 33-year period. Eight (18%) developed brain metastases during the course
      of their disease. The authors reviewed the clinical and radiologic features of
      six of these cases, for whom complete clinical information and imaging studies
      were available. RESULTS: The median age at diagnosis of malignant melanoma was 15
      years (range, 11-21 years). Brain metastases developed a median of 20 months
      (range, 0-50 months) after diagnosis and were preceded by metastases to other
      organs in 5 patients. In most cases, lesions were supratentorial and multiple.
      Most showed radiologic signs of intralesional hemorrhage. All patients received
      whole brain radiotherapy, and one had surgical resection. Three patients received
      chemotherapy. Five patients died a median of 5 months (range, 2-10 months) after
      diagnosis of brain involvement. One patient, who had a single brain metastasis at
      diagnosis, is alive more than 34 months later. CONCLUSIONS: Brain metastases
      develop in a significant proportion of children with malignant melanoma and are
      associated with a poor outcome. The incidence, features, and outcome in children
      do not appear to differ from those in adults.

PMID- 9191537
TI  - Psychometric analysis of the Functional Assessment of Cancer Therapy-General
      (FACT-G) scale in a rural sample.
AB  - BACKGROUND: Quality of life for persons with cancer has been studied extensively
      in urban populations. The Functional Assessment of Cancer Therapy-General (FACT
      G) scale was developed for use in clinical trials. The authors tested the
      psychometric properties of the FACT-G scale in a sample of rural cancer patients.
      METHODS: A systematic replication of the 1993 study by Cella et al., in which
      FACT-G was developed, was employed to assess the reliability, validity, and
      factor structure of the scale. RESULTS: The reliability and validity of the FACT
      G scale for evaluating rural cancer patients was determined to be sufficient for
      research purposes. The factor structure was the same as that reported by Cella et
      al. CONCLUSIONS: The FACT-G scale is appropriate for use in studies of the
      quality of life of rural cancer patients.

PMID- 9191538
TI  - The search continues--an ideal marker of GFR.

PMID- 9191539
TI  - Trade-offs in mass spectrometry.

PMID- 9191541
TI  - Genetic mutations of butyrylcholine esterase identified from phenotypic
      abnormalities in Japan.
AB  - We have identified 12 kinds of genetic mutations of butyrylcholine esterase
      (BCHE) from phenotypic abnormalities, showing that BCHE activities were deficient
      or diminished in sera. These genetic mutations, detected by PCR-single-strand
      conformation polymorphism analysis and direct sequencing, consisted of one
      deletion (BCHE*FS4), nine missense (BCHE*24 M, *1005, *250P, *267R, *330I, *365R,
      *418S, *515C, *539T), and two nonsense mutations (BCHE*119STOP, *465STOP). All of
      the individuals deficient in serum BCHE activity were homozygous for silent genes
      (6 of 6). Fifty-eight percent of the individuals (31 of 53) with slightly reduced
      serum BCHE activity were heterozygous for silent genes. They also showed a higher
      frequency (47% as allele frequency) of the K-variant than the general population
      (17.5%). Finally, we confirmed low serum BCHE activity in 10 of 23 individuals
      heterozygous for silent genes.

PMID- 9191540
TI  - Denaturing gradient-gel electrophoresis screening of familial defective
      apolipoprotein B-100 in a mixed Asian cohort: two cases of arginine3500-
      >tryptophan mutation associated with a unique haplotype.
AB  - The Arg-to-Trp substitution at codon 3500 in the apolipoprotein (apo) B-100 gene
      is established as a cause of familial defective apo B-100 (FDB), a functional
      mutation, resulting in reduced LDL receptor binding and manifest
      hypercholesterolemia. In a search for similar mutations in 163 Malaysians, we
      screened the putative receptor-binding region (codons 3456-3553) of the apo B-100
      gene by PCR amplification and denaturing gradient-gel electrophoresis. Four
      single-base mutations were detected and confirmed by DNA sequencing. Two females,
      a Chinese and a Malay, had the same CGG3500-->TGG mutation, resulting in an
      Arg3500-to-Trp substitution. This is the second published report of such an
      independent mutation involving the same codon as the established Arg3500-to-Gln
      mutation. The two other mutations detected, CTT3517-->CTG and GCC3527-->GCT,
      resulted in degenerate codons with no amino acid substitutions. All four
      mutations were associated with a unique apo B haplotype, different from those
      found in Caucasian FDB patients but concurring with that previously reported for
      two other Asians with FDB.

PMID- 9191542
TI  - Use of polymerase chain reaction to identify pneumococcal infection associated
      with hemorrhage and shock in two previously healthy young children.
AB  - A PCR assay was developed for detection of Streptococcus pneumoniae in clinical
      specimens including blood and paraffinized tissues. We were able to detect one
      organism of purified DNA or 4.5 colony-forming units in blood. The primers did
      not cross-react with other upper respiratory tract streptococci or with pathogens
      commonly found in clinical specimens. This assay was used in an investigation of
      an outbreak of severe illness characterized by septic shock and hemorrhage in
      previously healthy children. PCR detected S. pneumoniae in cerebrospinal fluid
      and autopsy tissues of the two infants who died. The findings from this assay
      indicated that PCR offers increased specificity and sensitivity over latex
      agglutination and counterimmunoelectrophoresis and should prove useful in the
      identification of additional cases of severe illness caused by S. pneumoniae.

PMID- 9191543
TI  - Rapid and large-scale method to detect K-ras gene mutations in tumor samples.
AB  - We have developed a rapid and large-scale method for the detection of K-ras gene
      mutations in tumors. First, DNA is amplified by an asymmetric PCR; second, the
      single-strand dinitrophenyl (DNP)-labeled amplified DNA is hybridized
      specifically to oligonucleotide probes affixed on a tube. Finally, perfectly
      matched duplexes are easily detected by a monoclonal anti-DNP antibody bearing
      125I. The usefulness of this technique is illustrated by analyzing K-ras codon 12
      mutations in human colorectal samples. This reliable assay procedure can be
      applied to the rapid screening of virtually any genetic disease caused by
      previously described point mutations.

PMID- 9191544
TI  - Enzyme immunoassay for measuring 25-hydroxyvitamin D3 in serum.
AB  - We developed a rapid, competitive enzyme immunoassay (EIA) for measuring 25
      hydroxyvitamin D3 [25(OH)D3] in serum. The EIA was based upon 25(OH)D3-3
      hemisuccinate covalently coupled to secondary amino groups grafted onto the
      polystyrene surface of microtiter wells. Optimal coupling conditions were
      established, and we found that inclusion of 40 mumol/L chloramine T, an agent not
      previously described for use in coupling to these plates, resulted in both more
      reproducible coupling as well as more than a twofold increase in the coupling
      efficiency. Before EIA, 25(OH)D3 was extracted from the serum samples by
      acetonitrile, and the redissolved extract was incubated with polyclonal rabbit
      antibody raised against 1,25-dihydroxyvitamin D3-3-hemisuccinate conjugated to
      bovine serum albumin. Peroxidase-labeled antibody raised in goat against rabbit
      immunoglobulins was used for detection. The detection limit of the EIA was 4.4
      micrograms/L; recovery 102%; on-plate CV 11%; within-run CV including extraction
      12%, and between-run CV 15%. There was no clinically important cross-reactivity
      with other vitamin D metabolites, and results obtained by the EIA were compared
      with results obtained by a previously described RIA.

PMID- 9191545
TI  - Growth hormone (GH) assays: influence of standard preparations, GH isoforms,
      assay characteristics, and GH-binding protein.
AB  - The impact of the adoption of the new biosynthetic growth hormone (GH) WHO
      International Reference Preparation (IRP 88/624), and the recommendation to
      report results in microgram/L instead of mU/L, is described. Conversion factors
      were determined by comparing both the linear and nonlinear relations of the GH
      values. The Pharmacia polyclonal IRMA (p-IRMA) and the DELFIA monoclonal time
      resolved immunofluorometric assay (trIFMA) with kit calibrators calibrated either
      against the pituitary-derived WHO IRP 80/505 or the new 88/624 were evaluated.
      Conversion factors of 4.17 mU/L = 1 microgram/L for the p-IRMA and 4.31 mU/L = 1
      microgram/L for the trIFMA were necessary. Different cross-reactivity patterns
      for the deaminated and dimer 22-kDa, 20-kDa, and 17-kDa GH isoforms were found.
      Expected GH recovery was similar when the measured values were adjusted according
      to the results of the cross-reactivity study.

PMID- 9191546
TI  - Misleading results from immunoassays of serum free thyroxine in the presence of
      rheumatoid factor.
AB  - A novel interference with measurements of serum free thyroxine (FT4) caused by
      rheumatoid factor (RhF) is described. We found misleading, sometimes gross,
      increases of FT4 results in 5 clinically euthyroid elderly female patients with
      high RhF concentrations. All 5 patients had high FT4 on Abbott AxSYM or IMx
      analyzers. "NETRIA" immunoassays gave misleading results in 4 of the 5 patients;
      Amerlex-MAB in 2 of 4 patients; AutoDELFIA in 2 of the 5; and Corning ACS-180 and
      Bayer Diagnostics Immuno 1 in 1 of the 5. BM-ES700 system results for FT4 in
      these women remained within the reference range. Results for serum T4, thyroid
      stimulating hormone, free triiodothyronine, thyroid-hormone-binding globulin, and
      FT4 measured by equilibrium dialysis were normal in all 5 patients. Drugs,
      albumin-binding variants, and anti-thyroid-hormone antibodies were excluded as
      interferences. Addition to normal serum of the RhF isolated from each of the 5
      patients increased the apparent FT4 (Abbott AxSYM). Screening of 83 unselected
      patients demonstrated a highly significant positive correlation between FT4
      (Abbott AxSYM) and RhF concentrations. Discrepant, apparently increased FT4 with
      a normal result for thyroid-stimulating hormone should lead to measurement of the
      patient's RhF concentration.

PMID- 9191547
TI  - Free triiodothyronine concentration in serum of 1050 euthyroid children is
      inversely related to their age.
AB  - Free triiodothyronine was assayed in serum of 1050 euthyroid children with the
      Amerlex-MAB method. We studied 50 samples for each year of age, from < 1 to 20,
      and no child had more than one sample taken. A gradient of values was observed,
      increasing by 31% from 5.04 pmol/L as the mean of 20-year-old patients to 6.59
      pmol/L in the serum of children younger than 1 year. For practical reasons the
      lower normal limit was proposed to remain at 3.4 pmol/L for all patients; the
      higher limit can be set at 8.3 (0 to 3 years), 7.8 (4 to 7 years), 7.1 (8 to 11
      years), 6.8 (12 to 15 years), and 6.7 (16 to 19 years). Preferably, the
      regression line of the mean + 2 SD can be used, resulting in a high normal limit
      of 8.3 pmol/L at birth to 6.3 pmol/L at 20 years, decreasing by 0.1 pmol/L per
      year.

PMID- 9191548
TI  - Evaluation of the Menarini-Arkray HA 8140 hemoglobin A1c analyzer.
AB  - We describe a multinational evaluation of the Menarini-Arkray HA 8140 hemoglobin
      (Hb) A1c analyzer, which utilizes a high degree of automation, including bar code
      reading, cap piercing, and whole-blood sampling. With-in- and between-batch CVs
      were < 2%. Linearity was confirmed throughout the working range of the analyzer.
      Common Hb variants, including Hb S, Hb C, and Hb F, did not interfere with the Hb
      A1c separation, and the potentially interfering labile Schiff base was
      effectively removed during the chromatographic procedure. The HA 8140 analyzer
      displayed good correlation to the Bio-Rad Variant analyzer, Tinaquant
      immunoassay, affinity chromatography, and an optimized "in-house" HPLC Hb A1c
      method. The methods when compared by Altman and Bland plots showed bias (upper,
      lower 95% confidence limits) of: Variant minus HA 8140 = 0.99 (0.23, 1.74),
      Tinaquant minus HA 8140 = 0.14 (-0.71, 0.98); affinity minus HA 8140 (after log
      transformation) = 1.13 (0.90, 1.41), and "in house" HPLC minus HA 8140 (after log
      transformation) = 0.91 (0.82, 1.01).

PMID- 9191549
TI  - Cardiac troponin I, cardiac troponin T, and creatine kinase MB in dialysis
      patients without ischemic heart disease: evidence of cardiac troponin T
      expression in skeletal muscle.
AB  - Serum cardiac troponin T (cTnT) concentrations are frequently increased in
      chronic dialysis patients as measured by the first-generation ELISA immunoassay,
      as is creatine kinase (CK) MB mass in the absence of acute ischemic heart
      disease. We designed this study to compare four serum markers of myocardial
      injury [CK-MB mass, first-generation ELISA cTnT, second-generation Enzymun cTnT,
      and cardiac troponin I (cTnI)] in dialysis patients without acute ischemic heart
      disease. We also evaluated skeletal muscle from dialysis patients as a potential
      source of serum cTnT. No patients in the clinical evaluation group (n = 24)
      studied by history and by physical examination, electrocardiography, and two
      dimensional echocardiography had evidence of ischemic heart disease. Biochemical
      markers were measured in serial predialysis blood samples with specific
      monoclonal antibody-based immunoassays. For several patients at least one sample
      measured above the upper reference limit: CK-MB, 7 of 24 (30%); ELISA cTnT, 17 of
      24 (71%); Enzymun cTnT, 3 of 18 (17%); and cTnI, 1 of 24 (4%). In a separate
      group of dialysis patients (n = 5), expression of cTnT, but not cTnI, was
      demonstrated by Western blot analysis in 4 of 5 skeletal muscle biopsies. Chronic
      dialysis patients without acute ischemic heart disease frequently had increased
      serum CK-MB and cTnT. The specificity of the second-generation cTnT (Enzymun)
      assay was improved over that of the first-generation (ELISA) assay; cTnI was the
      most specific of the currently available biochemical markers. cTnT, but not cTnI,
      was expressed in the skeletal muscle of dialysis patients.

PMID- 9191550
TI  - Semiautomated procedures for evaluation of carbohydrate-deficient transferrin in
      the diagnosis of alcohol abuse.
AB  - Carbohydrate-deficient transferrin (CDT) may now be the most valuable biological
      marker for diagnosis of alcohol abuse. We compared the diagnostic performance of
      two new CDT tests, Axis %CDT turbidimetric immunoassay (TIA) and Axis %CDT HPLC,
      against Specialty Laboratories' isoelectric focusing/immunoblotting/laser
      densitometry (IEF/IB/LD). Both Axis tests include one-half the concentration of
      trisialotransferrin isoforms in their CDT quantitation schemes. Considering an
      alcohol abuse prevalence of 7%, Axis %CDT TIA shows a sensitivity of 87% at 98%
      specificity and a positive predictive value (PPV) of 0.75; %CDT HPLC shows a
      sensitivity of 87% at 100% specificity for a PPV of 1, and the IEF/IB/LD shows
      81% sensitivity at 94% specificity for a PPV of 0.5. All three CDT tests show the
      same negative predictive value (0.98). Both Axis procedures perform better than
      IEF/IB/LD in the diagnosis of alcohol abuse; %CDT TIA is available in several
      semiautomated, cost-effective formats.

PMID- 9191551
TI  - Cardiac troponin I and T alterations in hearts with severe left ventricular
      remodeling.
AB  - Cardiac troponin T (cTnT) and troponin I (cTnI) have been suggested as new, more
      specific markers of myocardial cellular damage. The objective of this study was
      to examine how the distributions of cTnI and cTnT were affected in postinfarction
      left ventricular remodeled (LVR) myocardium. At 2 months postinfarct in a porcine
      heart failure model, both Western blot and biochemical assay analyses were
      performed on left ventricular myocardium remote from the infarct zone in ligation
      animals (n = 8). Results were compared with data from the left ventricular
      myocardium from similar sized healthy (control) pigs (n = 7). Autoradiograms from
      Western blot analysis showed that the protein mass for cTnI and cTnT in LVR
      hearts decreased 80% (P < 0.001) and 40% (P < 0.02), respectively, when compared
      with nondiseased tissue. Similarly, the concentrations for cTnI and cTnT in LVR
      hearts decreased 42% (P < 0.05) and 70% (P < 0.001), respectively, compared with
      nondiseased normal tissue. The clinical assumption is that the appearance of cTnI
      and cTnT in the blood is proportional to chronic loss of cTnI and cTnT from
      injured myocardium associated with left ventricular remodeling.

PMID- 9191552
TI  - Microalbuminuria and borderline-increased albumin excretion determined with a
      centrifugal analyzer and the Albumin Blue 580 fluorescence assay.
AB  - We report a new automated fluorescence assay for determination of albumin in
      urine. The dye Albumin Blue 580 specifically binds to albumin with exhibition of
      strong red fluorescence. The albumin concentration is calculated from emission
      intensity at 616 nm (excitation at 590 nm) and a calibration curve. Two Cobas
      Fara programs cover working ranges of 2-200 and 1-50 mg/L with detection limits
      of 1.4 and 0.4 mg/L, respectively. Within-run CVs (n = 10) ranged from 1.7% (189
      mg/L) to 8.9% (7.2 mg/L) for 2-200 mg/L and from 2.9% (43.3 mg/L) to 5.7% (2.3
      mg/L) for the 1-50 mg/L range. A test of urine samples (n = 100) submitted to
      routine analysis gave results that agreed well with those by the Behring
      nephelometric assay: AB 580 = 0.922 (+/-0.010) BNA + 4.16 (+/-0.78). No
      interference was detected from other urine components, including several proteins
      and 46 drugs. The high specificity and sensitivity make the method ideal for
      determination of microalbuminuria. In addition, the method is fast, inexpensive,
      and well-suited for clinical laboratory application and thus may be used instead
      of immunoassays.

PMID- 9191553
TI  - Highly sensitive gas chromatographic analysis of ethanol in whole blood, serum,
      urine, and fecal supernatants by the direct injection method.
AB  - A highly sensitive, reproducible, and rapid gas chromatographic method for
      ethanol determination in various biological specimens (human whole blood, serum,
      urine, and fecal supernatants) was developed. The method involves direct
      injection of the biological specimen into the gas chromatograph, without any
      pretreatment. Contamination of the gas chromatographic column with nonvolatile
      material was prevented by the use of a glass liner in the injector. This liner,
      which acted as a precolumn, was partly filled with small glass beads. Injection
      was performed in between the glass beads. More than 50 injections of the various
      biological specimens could be done before the liner had to be replaced by a new
      one. This injection technique between glass beads allows direct injection of
      large sample volumes up to 10 microL without disturbing the gas chromatographic
      separation. Injection of these large sample volumes made the method very
      sensitive. The detection limit for ethanol amounted to 0.1 mg/L (2 mumol/L) when
      using an injection volume of 5 microL. Attention has also been paid to
      simultaneously monitoring ethanol, methanol, acetaldehyde, and acetone in blood
      and urine of control subjects.

PMID- 9191554
TI  - Determination of D-lactate by enzymatic methods in biological fluids: study of
      interferences.
AB  - Analysis of nondeproteinized samples with an enzymatic method to determine D
      lactate indicated interferences. The presence of L-lactate dehydrogenase (LD) and
      L-lactate in the sample led to underestimation of D-lactate content when a sample
      blank was processed and overestimation when it was omitted. We proved that this
      interference is not due to lack of D-LD stereospecificity. Moreover, assessment
      of D-LD and L-LD KM for NAD+ allowed us to rule out the different affinities for
      this coenzyme as a cause of the interference. Our results underline the
      importance of deproteinizing samples for D-lactate analysis when enzymatic
      methods are used. The ultrafiltration procedure we propose is convenient and
      shows acceptable mean recovery (108%) and good imprecision (within-run CV = 4.2%
      and 3.0% for D-lactate at 31 and 107 mumol/L, respectively; between-run CVs were
      7.3% at 49 mumol/L D-lactate and 3.1% at 115 mumol/L D-lactate).

PMID- 9191555
TI  - Initial evaluation of cystatin C measurement by particle-enhanced
      immunonephelometry on the Behring nephelometer systems (BNA, BN II).
AB  - Serum cystatin C has been suggested as a new marker of glomerular filtration rate
      (GFR). We describe a fully automated and rapid particle-enhanced nephelometric
      immunoassay (PENIA) for measuring serum cystatin C on the Behring nephelometer
      systems (BNA, BN II). Each sample is analyzed in 6 min with as many as 75 samples
      per batch. The assay covers the range 0.23-7.25 mg/L, up to seven times the upper
      limit of normal. The intra- and interassay imprecision are < 3.3% and < 4.5%,
      respectively. There is absolute linearity across the assay range (r2 = 0.997),
      with analytical recovery by cystatin C addition between 95% and 109% (mean 102%).
      Hemoglobin (< or = 8.0 g/L), bilirubin (< or = 488 microL), triglycerides (< or =
      23 mmol/L), rheumatoid factor (< or = 2000 kIU/L), and myeloma paraprotein (< or
      = 41 g/L) do not interfere with the assay. This assay agreed well with an in
      house particle-enhanced turbidimetric immunoassay (PETIA) (mean difference = 1.73
      +/- 2.10) and a commercial PETIA (mean difference = 1.13 +/- 0.86). This is a new
      assay by which cystatin C may be effectively used as a marker of GFR estimation.

PMID- 9191556
TI  - Gastrointestinal absorption, tissue retention, and urinary excretion of dietary
      aluminum in rats determined by using 26Al.
AB  - We used accelerator mass spectrometry (AMS) and 26AI to study the plasma
      concentration, urinary excretion, and retention in bone, brain, and liver of a
      single dose of a dietary concentration of aluminum ingested either with or
      without citrate by 2-month-old Wistar rats. In the absence of citrate, cumulative
      urinary excretion and skeleton retention were each approximately 0.05% of the
      total 26AI dose ingested. 26AI retention in brain and liver were approximately 4
      x 10(-8) and 2 x 10(-6), respectively. Concomitant citrate intake increased these
      median values by about two- to fivefold, although this factor was highly variable
      in individual rats. Independent of citrate administration, 90% of the 26AI
      excreted in urine (measured cumulatively over 30 days) was excreted within the
      first 48 h. Uptake by bone was rapid (approximately 1 h) and permanent over the
      30-day duration of the experiment.

PMID- 9191557
TI  - Simultaneous identification and quantitation of codeine, morphine, hydrocodone,
      and hydromorphone in urine as trimethylsilyl and oxime derivatives by gas
      chromatography-mass spectrometry.
AB  - Following enzymatic hydrolysis of urine, a gas chromatography-mass spectrometry
      method for the simultaneous determination of codeine, morphine, hydrocodone, and
      hydromorphone uses hydroxylamine to form oxime derivatives of the keto-opiates
      (i.e., hydrocodone, hydromorphone, oxycodone, and oxymorphone). These
      trimethylsilyl-derivatized forms no longer interfere with the detection and
      quantitation of codeine and morphine. Samples are extracted on solid-phase
      columns and quantitated by deuterated internal calibrations of each analyte with
      selected ion monitoring. Codeine, morphine, hydrocodone, and hydromorphone are
      completely separated, allowing simultaneous quantitation without interference and
      a chromatographic analysis time < 9 min.

PMID- 9191558
TI  - Evaluation of selected-ion storage ion-trap mass spectrometry for detecting
      urinary anabolic agents.
AB  - Limits of detection are important issues for GC/MS screening for anabolic agents
      and for confirmation of various drugs of abuse. We compared a quadrupole ion trap
      (QIT) operated in two different selected-ion storage modes and a quadrupole mass
      filter (QMF) operated in the selected-ion monitoring mode. Results with the model
      compound tetrachlorobenzene indicate that, for simultaneous monitoring of more
      than four ions, the QIT operated in a frequency-modulated selected-ion storage
      mode has better limits of detection than the QMF. Use of a single-ion storage
      technique gave results similar to those of the QMF. We also evaluated both QIT
      selected-ion storage approaches for the limits of detection of the trimethylsilyl
      derivatives of four anabolic steroid metabolites and the beta-agonist
      clenbuterol. We found no improvement in detection limits over that of a similar
      method with selected-ion monitoring and a QMF when four anabolic steroid
      metabolites and clenbuterol were extracted from a urine matrix. The lack of
      improvement in the limit of detection resulted from matrix background signals at
      masses similar to those of the steroids.

PMID- 9191559
TI  - Comparison of two assays for measuring LDL cholesterol.
AB  - The purpose of this study was to evaluate the LipiDirect assay (L-LDL) against
      the Direct LDL immunoseparation method (D-LDL) and beta quantification (BQ-LDL)
      for measurement of LDL cholesterol (LDL-C) in patients with normo- and
      hypertriglyceridemia. Samples from 156 patients [triglyceride (Tg) range 0.61
      9.95 g/L] were assayed for LDL-C concentrations with the three methods. An
      additional seven patients with type III hyperlipidemia and 25 paired sera from
      fasting and nonfasting individuals also were analyzed by the three methods. Both
      assays displayed excellent precision. The mean LDL-C value from L-LDL was
      significantly higher than BQ-LDL and D-LDL in normo- and hypertriglyceridemic
      samples (P < 0.001). The mean absolute bias of L-LDL vs BQ-LDL was 12.7% for Tg <
      4 g/L and 30.6% for Tg > or = 4 g/L, compared with 6.2% and 12.5%, respectively,
      for D-LDL. L-LDL correctly classified only 68% of patients with LDL-C < 1.30 g/L
      and 57% of patients with LDL-C between 1.30-1.59 g/L as compared with 98% and
      93%, respectively, for D-LDL (P < 0.001). In patients with type III
      hyperlipidemia, L-LDL had a 130% positive bias with BQ-LDL as compared with a 14%
      negative bias for D-LDL. With all three methods there were no significant
      differences between samples from fasting and nonfasting individuals. On the basis
      of these findings, the D-LDL assay appears to be superior to the L-LDL assay.

PMID- 9191560
TI  - Evaluation of two homogeneous methods for measuring high-density lipoprotein
      cholesterol.
AB  - We evaluated the performance of two homogeneous assays for quantifying HDL
      cholesterol (HDL-C) and compared them with the phosphotungstic acid (PTA)/ MgCl2
      assay. Both homogeneous HDL-C assays were precise, having a within-run CV of <
      1.20% and a between-run CV of < 4.07%. The HDL-C values (y) measured by the two
      homogeneous methods correlated well with those by the PTA/MgCl2 method (x): y =
      1.00x + 64.98 mg/L, r = 0.987, Sy/x = 27.99 mg/L (n = 152) for the polyethylene
      glycol-modified enzymes/alpha-cyclodextrin sulfate (PEGME) assay (Kyowa), and y =
      0.84x + 106.51 mg/L, r = 0.984, Sy/x = 26.10 mg/L (n = 152) for the polyanion
      polymer/detergent (PPD) assay (Daiichi). The specificity of the PEGME method
      seemed better than that of the PPD method, as the PPD method was markedly
      interfered with by supplemental LDL-C. Addition of 20 g/L triglycerides produced
      a negative error of approximately 18% in both homogeneous assays. Bilirubin and
      hemoglobin had little influence on the PEGME method; hemoglobin had little effect
      on the PPD method. Bilirubin, however, markedly decreased the readings by the PPD
      method. We found the PEGME assay superior to the PPD assay for routine HDL-C
      testing, because the PPD assay is relatively inaccurate and not specific.

PMID- 9191561
TI  - Assessment of a portable clinical blood analyzer during space flight.
AB  - This study was designed to validate the utility of a commercial portable clinical
      blood analyzer (PCBA) in ground-based studies and on the space shuttle. Ionized
      calcium, pH, electrolytes, glucose, and hematocrit were determined. Results
      agreed well with those from traditional laboratory methods, and the PCBA
      demonstrated good between-day precision for all analytes. In-flight analysis of
      control samples revealed differences in one analyte (sodium). There were few
      changes in crew members' results during flight, and these were expected.
      Potassium increased in flight compared with before flight, and potassium, pH, and
      hematocrit decreased after flight. Ionized calcium was decreased in flight and on
      landing day. Changes during flight were likely related to sample collection
      technique. Postflight changes likely reflected the fluid redistribution that
      occurs after exposure to weightlessness. These data confirm that the PCBA is a
      reliable instrument for most analytes, and can provide important medical data in
      remote locations, such as orbiting spacecraft.

PMID- 9191563
TI  - Platelet distribution width for differential diagnosis of thrombocytosis.
AB  - Differential diagnosis of thrombocytosis is not always obvious. The routine
      clinical chemistry laboratory classically provides only limited help in
      distinguishing between reactive thrombocytosis (RT) and autonomous
      thrombocytosis, where platelet production escapes normal regulatory processes,
      and which is seen in myeloproliferative diseases (MPD) such as essential
      thrombocythemia and polycythemia vera. We explored the clinical use of platelet
      distribution width (PDW) in the differential diagnosis of thrombocytosis. During
      a 3-month period, 250 patients presenting with a platelet count > 500 x 10(9)/L
      were studied; 174 were classified as having RT, 42 had a diagnosis of MPD, and 34
      patients were excluded because they had a hemopathy different from MPD, and
      either did or did not present a known etiologic factor for RT. First, we
      determined that in the RT group the value of PDW was closely linked to both mean
      platelet volume (MPV) and platelet count (PLT) (PDW = 79.5-0.005 PLT -3.5 MPV; r
      = 0.848, R2 = 0.720). Therefore a new parameter, PDWresidual was defined
      (PDWresidual = PDWobserved -PDWexpected). Second, the discrimination between
      reactive and autonomous thrombocytosis obtained with PDWresidual was compared
      with that obtained with either PDW, MPV, or PLT. PDWresidual provided much more
      powerful than each of the other parameters used separately: 76% of MPD patients
      had a PDWresidual above the 95th percentile value of the RT population and none
      of the MPD patients had a PDWresidual below the 50th percentile. Thus, the
      combined interpretation of PLT, MPV, and PDW through the use of a PDWresidual
      appears highly useful in the differential diagnosis of thrombocytosis. Also,
      through simple modeling, more information can be drawn from parameters such as
      PDW that hitherto were mostly discarded as being without clinical interest.

PMID- 9191562
TI  - Reference values for retinol, tocopherol, and main carotenoids in serum of
      control and insulin-dependent diabetic Spanish subjects.
AB  - To establish reference ranges for use in clinical and epidemiological studies, we
      determined concentrations of retinol, alpha-tocopherol, beta-carotene, alpha
      carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene in 450 Spanish
      control subjects and 123 Spanish patients with insulin-dependent diabetes
      mellitus (IDDM). Results were grouped according to sex, and samples were
      collected throughout the year. Concentrations of retinol were significantly lower
      and beta-carotene and alpha-carotene were higher in women than in men, both in
      controls and IDDM subjects, whereas beta-cryptoxanthin concentrations were higher
      only in control women. Conditional logistic regression analysis showed that
      retinol, beta-carotene, and lycopene were the variables associated with diabetes.
      In comparison with other populations, our controls showed, in general, ordinary
      concentrations of retinol, comparatively low beta-carotene and high beta
      cryptoxanthin concentrations, and a relatively high alpha-tocopherol/ cholesterol
      ratio.

PMID- 9191564
TI  - Are cystatin C and beta 2-microglobulin better markers than serum creatinine for
      prediction of a normal glomerular filtration rate in pediatric subjects?

PMID- 9191565
TI  - Interference of methylene blue with CO-Oximetry of hemoglobin derivatives.

PMID- 9191566
TI  - Determination of MEGX by HPLC with fluorescence detection.

PMID- 9191567
TI  - PCR-based test for two cystic fibrosis mutations (A455E, 711 + 1 G-->T) common
      among French Canadians.

PMID- 9191568
TI  - Effect of high room temperature on urinary iodine assay.

PMID- 9191569
TI  - Clinical evaluation of the Cell-Dyn 1700CS blood counter.

PMID- 9191570
TI  - Analytical performance of the Sanofi Access cardiac troponin-I procedure.

PMID- 9191571
TI  - Comparison of methods for measurement of Na+/U+ countertransport across the
      erythrocyte membrane.

PMID- 9191572
TI  - Antioxidant activity of the stilbene astringin, newly extracted from Vitis
      vinifera cell cultures.

PMID- 9191573
TI  - Microalbumin and freezing.

PMID- 9191574
TI  - Handling of blood samples for determination of thalidomide.

PMID- 9191576
TI  - Undisclosed radioactivity in specimens: how much of a problem?

PMID- 9191575
TI  - Nonisotopic method for precise detection of (CAG)n repeats.

PMID- 9191577
TI  - Rapid qualitative TSH test to screen for primary hypothyroidism.

PMID- 9191578
TI  - Pitfalls in discriminating sulfhemoglobin from methemoglobin.

PMID- 9191579
TI  - Hair iron content: possible marker to complement monitoring therapy of iron
      deficiency in patients with chronic inflammatory bowel disease?

PMID- 9191580
TI  - Equivalence of critical error calculations and process capability index Cpk.

PMID- 9191581
TI  - Objective measurement of sleepiness in summer vacation long-distance drivers.
AB  - The study investigated whether sleepiness at the wheel is a problem in non
      commercial drivers going on summer vacation. All drivers, who stopped at a rest
      area on a large European freeway while one of the interviewers was available,
      were systematically approached and asked to respond to a questionnaire. All
      subjects who had driven at least 400 km (240 miles), whose age was between 20 and
      46 years of age, and who agreed to participate were asked to undergo a longer
      investigation that included a short sleep/wake diary describing overall sleep
      habits during the year, a sleep/wake log covering the days just prior to
      departure, an analog visual scale indicating sleepiness at time of interview, and
      a polygraphically monitored two nap sleep test (TNST). A control group was
      recruited that consisted of subjects of the same age range, normal sleep habits,
      and normal nocturnal sleep time before administration of the TNST. One hundred
      and four drivers (2 women) participated between 08:00 and 20:00 h. The total
      group was subdivided into 6 subgroups based upon the time of day of their
      investigation (08:00-10:00 h, 10:01-12:00 h, etc.). The control group included 50
      men with 50-55% of control subjects, relative to the total number of index-cases,
      in each subgroup. Eighty-eight percent (n = 92) of studied drivers had
      experienced acute sleep deprivation within one day prior to departure due to the
      planned long driving. The TNST demonstrated that, overall, drivers had a
      significantly shorter sleep latency in nap 1 and nap 2 than controls, had a
      significantly longer sleep duration in nap 1 and nap 2, and there was a
      significant correlation between the sleep debt prior to departure and the sleep
      stage reached during the TNST. It is concluded that the TNST is a test which
      allows the objective study of sleepiness in drivers without the burden of the
      multiple sleep latency test. Many drivers are excessively sleepy when making long
      summer vacation journeys.

PMID- 9191582
TI  - Heart rate variability: sleep stage, time of night, and arousal influences.
AB  - Spectral analysis was used to assess heart rate variability in consecutive 5-min
      epochs during the night in 12 normal adults. Simultaneous time coding of EEG and
      digitized EKG allowed examination of heart rate variability as a function of
      sleep stage, time of night and presence of EEG arousal. The results replicated
      previous studies in showing increases in high frequency components and decreases
      in low frequency components of heart rate variability across NREM sleep stages
      and opposite changes in REM sleep and wake. These results are consistent with
      sympathetic nervous system activation during REM sleep and wake periods. The
      shift in heart rate variability seen during REM sleep began in NREM sleep several
      minutes prior to standardly scored REM and often continued beyond the end of REM
      sleep. EEG arousals during Stage 2 and to some extent REM sleep were also
      associated with changes in heart rate variability which were consistent with
      sympathetic activation. An examination of beat to beat intervals in proximity to
      EEG arousals showed heart rate acceleration at least 10 beats prior to the EEG
      arousal. The arousal data along with Stage 2 sleep transition data support the
      contention that increases in central nervous system sympathetic activity precede
      and possibly play a role in the initiation of REM sleep and arousals during
      sleep.

PMID- 9191583
TI  - Sleep latency measures of caffeine effects during sleep deprivation.
AB  - Studies of stimulants during sleep deprivation have used performance assessment
      batteries (PABs) and occasionally the multiple sleep latency test (MSLT) as
      measures. Another type of sleep latency test, the maintenance of wakefulness test
      (MWT), assesses ability to remain awake without assistance, rather than ability
      to go to sleep. The MWT previously has not been used in studies of stimulants
      during sleep deprivation. This study of caffeine during 64 h without sleep
      included a PAB, the MSLT, and a single MWT trial per day. The PAB and the MSLT
      were sensitive to caffeine effects during the first 24 h without sleep. The MWT
      demonstrated that caffeine improved ability to remain awake even after 2 nights
      of sleep deprivation. Ability to go to sleep and ability to stay awake during
      sleep deprivation appear to be affected differently by caffeine. PAB testing may
      fail to detect this stimulant effect because technicians prevent subjects from
      nodding off during PAB testing, an external support not available to subjects
      during the MWT and also not available in many real-world work environments. The
      MWT was more sensitive to stimulant amelioration of sleep-deprivation effects.
      The findings need to be validated with MWTs at other times of day and with other
      stimulants.

PMID- 9191584
TI  - Caffeine effects on perceptual and motor processes.
AB  - The effects of a single dose of caffeine on specific information processing
      operations were examined by using a visual selective attention task in which
      subjects were asked to select between a left and right hand response on the basis
      of two different target letters. The target was presented on a predefined
      position in the visual field and was either presented alone or with flanker
      letters, calling for the correct, the incorrect or no specific response. A dose
      of 3 mg/kg body weight caffeine or lactose, dissolved in a cup of decaffeinated
      coffee, was administered double blind and deceptively to overnight abstinence
      coffee drinkers. Behavioural measures were supplemented by psychophysiological
      measures. The present results replicated the basic findings obtained in this
      paradigm. The results indicated that the time to localise the target decreased
      and response preparation started earlier after caffeine than after placebo. These
      caffeine effects did not interact with the time subjects spent on the task or
      with the reaction time distribution, which might be due to a high level of
      practice.

PMID- 9191585
TI  - Extracranial localization of intracranial interictal epileptiform activity using
      LORETA (low resolution electromagnetic tomography).
AB  - Besides the standard clinical methods of EEG waveshape analysis, mathematical
      models for reconstruction of dipolar sources from the digitized surface EEG have
      been introduced in epilepsy research. Although useful for localizing focal
      sources, these methods are inadequate for analyzing widespread epileptiform
      activity. A recently introduced alternative method called LORETA (low resolution
      electromagnetic tomography, Pascual-Marqui et al., 1994), directly computes the
      current distribution throughout the full brain volume, assuming that neighboring
      neuronal populations are simultaneously and synchronously activated. In
      mathematical terms the method selects the smoothest of all possible 3-dimensional
      current distributions, inherently introducing a certain amount of dispersion. In
      7 patients, undergoing simultaneous EEG recording from 10 intracranial (subdural)
      and 22 extracranial electrodes, 111 subdural discharges (61 subtemporal and 50
      lateral temporal) were identified. The exact time point of maximal intracranial
      activity was automatically identified, and the LORETA solution at that timepoint
      was computed from the surface EEG. Statistical comparison revealed significantly
      higher LORETA current density in the area corresponding to the subdurally
      recorded spike compared to other areas, and a more anterior and more medial
      LORETA location for subtemporal compared to lateral temporal spikes. This study
      indicates that the LORETA technique may become a useful method to localize
      electrical activity in the brain.

PMID- 9191586
TI  - Possibilities and limitations of magnetic source imaging of methohexital-induced
      epileptiform patterns in temporal lobe epilepsy patients.
AB  - The usefulness of MEG-based techniques in lateralizing and localizing the
      epileptogenic area was investigated in the present study. Spontaneous and
      methohexital-induced spikes were studied in a group of 15 patients with
      temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the
      magnetic source imaging was compared to the results of electrocorticographic
      (ECoG) recordings. Differences of drug-induced spike densities in the MEG
      recordings between both sides confirmed a similar lateralizing power of the MEG
      and ECoG recordings. Source location analyses based on a moving dipole model
      resp. a rotating dipole model were performed using a spherical head model. After
      subdivision of the volume of each patient's head, 8 cm3 cubicles containing at
      least 3 source locations were projected onto the individual MRI scan and resulted
      in source locations within or close to the presurgically defined primary
      epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital
      has the advantage of shortening the recording period as compared to recordings of
      interictal epileptiform discharges. However, the correlation analyses of spike
      densities from MEG and ECoG recordings and the source location analyses from MEG
      recordings indicate that spike generated in deep temporomesial structures may
      escape the MEG registration.

PMID- 9191587
TI  - Epileptiform and non-epileptiform paroxysmal activity from isolated cortex after
      functional hemispherectomy.
AB  - The relationship of acute complete cortical isolation to paroxysmal cerebral
      activity was examined in 16 patients with electrocorticography (ECOG) before and
      after functional hemispherectomy (FH). Burst-suppression activity appeared over
      isolated cortex in all cases, the severity of which could be increased by
      systemic administration of propofol or methohexital. Interictal epileptiform
      activity (EA) recorded from frontal or parietal-occipital cortex before FH
      invariably persisted after FH (11 cases). No EA was recorded before or after FH
      in 3 cases while in 2 cases EA appeared following FH which had not been present
      before FH. The intensity of burst-suppression activity was not related to the
      presence or absence of post-excision EA. In total, 30 disconnected cortices were
      recorded from; relative abundance of EA was increased in 10, unchanged in 17, and
      decreased in 3 cases. Unrelated to the induction of burst-suppression activity,
      cortical isolation may decrease the threshold for expression of interictal EA.

PMID- 9191588
TI  - Induction of burst-suppression and activation of epileptiform activity after
      methohexital and selective amygdalo-hippocampectomy.
AB  - Electrocorticography (ECOG) compared the effects of methohexital (MTH) and
      selective amygdalo-hippocampectomy (selAH) upon lateral temporal neocortical
      epileptiform activity (EA) in 31 patients with mesial temporal epilepsy. Pre
      excision ECOG showed independent neocortical EA before MTH in 12/31 and after MTH
      in 18/31. MTH (20-50 mg) activated neocortical EA in 12 cases and induced burst
      suppression (BS) over temporal neocortex in 14/31. Post-excision ECOG showed
      neocortical EA in 21/31 and BS in 27/31: compared with pre-excision ECOG before
      MTH, selAH activated neocortical EA in 15 cases. Significant correlations were
      found between presence of pre-excisional neocortical EA and presence of post
      excisional neocortical EA (P < 0.001) and between activation of pre-excisional
      neocortical EA by MTH and activation of (post-excisional) neocortical EA by selAH
      (P < 0.006). Presence or severity of BS in the post-excision ECOG was not
      correlated with presence, absence or activation of post-excisional EA. Presence
      of neocortical EA was significantly correlated with a higher pre-operative
      seizure frequency (P < 0.001) but not with duration of epilepsy nor surgical
      outcome. Both MTH and selAH can induce neocortical BS, likely through chemical
      and surgical disconnection of cortex, respectively. Unrelated to induction of BS,
      MTH and selAH appear to decrease threshold for expression of neocortical EA in a
      similar fashion.

PMID- 9191589
TI  - A systematic evaluation of the spherical model accuracy in EEG dipole
      localization.
AB  - This paper presents a study of the intrinsic localization error bias due to the
      use of a spherical geometry model on EEG simulated data obtained from
      realistically shaped models. About 2000 dipoles were randomly chosen on the
      segmented cortex surface of a particular subject. Forward calculations were
      performed using a uniformly meshed model for each dipole located at a depth
      greater than 20 mm below the brain surface, and locally refined models were used
      for shallower dipoles. Inverse calculations were performed using four different
      spherical models and another uniformly meshed model. It was found that the best
      spherical model lead to localization errors of 5-6 mm in the upper part of the
      head, and of 15-25 mm in the lower part. The influence of the number of
      electrodes upon this intrinsic bias was also studied. It was found that using 32
      electrodes instead of 19 improves the localization by 2.7 mm on average, while
      using 63 instead of 32 electrodes lead to improvements of less than 1 mm.
      Finally, simulations involving two simultaneously active dipoles (one in the
      vicinity of each auditory cortex) show localization errors increasing by about 2
      3 mm.

PMID- 9191590
TI  - Collagen fibril orientation in the human corneal stroma and its implications in
      keratoconus.

PMID- 9191591
TI  - Morphometric analysis of the choroid, Bruch's membrane, and retinal pigment
      epithelium in eyes with age-related macular degeneration.

PMID- 9191592
TI  - Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate
      of retinal precursor cells.
AB  - PURPOSE: To study the expression patterns of the homeobox genes Pax-6, Prox 1,
      and Chx10 during chick retinal development in vivo and in vitro. METHODS:
      Sections of paraformaldehyde-fixed, paraffin-embedded eyes were obtained at a
      range of developmental stages. In situ hybridization was carried out on tissue
      sections using digoxigenin-labeled sense and antisense RNA probes that recognize
      chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken
      Chx10 (which was cloned and sequenced as part of this study). Selected
      developmental stages were also studied by immunocytochemistry with antibodies
      against Pax-6 and Prox 1, and by Northern blot analysis using 32P-labeled probes.
      RESULTS: Until embryonic day (ED) 5, in situ hybridization shows widespread,
      diffuse distribution of all three genes. Between ED 6 and ED 8, however, they
      acquire distinct, topographically specific patterns of expression. The Prox 1
      signal is predominantly expressed in the prospective horizontal cell layer of the
      neuroepithelium, decreases vitreally, and is absent from ganglion cells and the
      prospective photoreceptor layer. Pax-6 is strongly expressed only in the
      prospective ganglion-cell and amacrine-cell regions at the same stages, and is
      not detected in prospective photoreceptors. Chx10 expression becomes concentrated
      in the future bipolar-cell region of the inner nuclear layer. Similar patterns
      are maintained by ED 15 through ED 18, after cell differentiation has taken
      place. Pax-6 and Prox 1 immunoreactive materials showed nuclear localization and
      a pattern of laminar distribution equivalent to that seen by in situ
      hybridization. CONCLUSIONS: These results suggest that the differentiated fate of
      retinal precursor cells may be influenced by Pax-6, Prox 1, or Chx10, this
      hypothesis is now being tested using dissociated chick embryo retinal cell
      cultures.

PMID- 9191593
TI  - Submicrometer precision biometry of the anterior segment of the human eye.
AB  - PURPOSE: To demonstrate the feasibility of measuring the anterior structures of
      the human eye by partial coherence interferometry and to determine its precision
      for eyes under normal and cycloplegic conditions. METHODS: The dual-beam version
      of partial coherence interferometry, a recently developed noninvasive optical
      ranging technique, enables high resolution measurements of several intraocular
      distances with unprecedented precision. A modified, more sensitive scanning
      version of this technique was used to assess the central and peripheral corneal
      thickness, the anterior chamber depth, and the lens thickness of 20 healthy,
      emmetropic to moderately myopic eyes. Furthermore the anterior structures of
      three eyes were measured under cycloplegia (1% cyclopentolate) to investigate the
      influence on the precision of this technique after suppression of residual
      accommodations. RESULTS: The mean geometric precision (standard deviation) of the
      measurement of the central corneal thickness was 0.29 micron (range, 0.22 micron
      to 0.38 micron) and 0.43 micron (range, 0.27 micron to 0.56 micron) for the
      peripheral corneal thickness at a distance 2 mm from its apex. The precision for
      measuring the anterior chamber depth and the lens thickness for fixation at
      infinity was 8.7 microns (range, 3.9 microns to 16.8 microns) and 8.9 microns
      (rang, 2.9 microns to 14.4 microns) for noncycloplegic eyes and 1.9 microns
      (range, 1.7 microns to 2 microns) and 1.4 microns (range, 0.7 micron to 1.8
      microns) for cycloplegic eyes, respectively. CONCLUSIONS: The dual-beam partial
      coherence interferometry enables fast, noninvasive, submicrometer precision
      biometry of the anterior segment of the eye. The precision of determining the
      anterior chamber depth and the lens thickness is more than one order of magnitude
      better than that of the currently used ultrasound and optical techniques, and it
      can be improved by a factor of 5 by using cycloplegia.

PMID- 9191594
TI  - Stiffness of the inferior oblique neurofibrovascular bundle.
AB  - PURPOSE: To assess the mechanical ability of the inferior oblique
      neurofibrovascular bundle (NFVB) to act as an ancillary origin for the inferior
      oblique muscle after anterior transposition. METHODS: Stress-strain relations and
      Young's modulus of elasticity, a measure of tissue stiffness, were determined for
      the NFVB in vitro, in situ, and in vivo in dynamic and static conditions. For
      comparison, similar studies were performed in vitro on the superior oblique
      tendon (SOT). RESULTS: Young's moduli for NFVB in situ (6.3 MPa [megapascals])
      and in vivo (11.8 MPa) were approximately 2 and 4 times greater (P < 0.05),
      respectively, than those of isolated NFVB in vitro at 5% to 10% dynamic strain (3
      MPa). In dynamic conditions, Young's moduli in vitro for the NFVB and the SOT
      were similar. CONCLUSIONS: The NFVB is a biomaterial that has stiffness
      properties similar to the SOT. Within the range of forces typical of normal eye
      movements (79 to 393 mN), the NFVB alone can tolerate forces of 98 mN at 0% to
      10% strain and 393 mN at 15% to 20% strain, based on dynamic in vitro analysis.
      The greater measured stiffness in situ and in vivo suggest that the NFVB in the
      intact orbit potentially has a resting strain of 15% to 20%, and additional
      tissues in parallel with the NFVB also contribute to total stiffness. These data
      support the hypothesis that the NFVB, acting alone or in concert with adjacent
      orbital tissues, may form an ancillary origin for the inferior oblique muscle
      after anterior transposition.

PMID- 9191595
TI  - Light scattering by donor lenses as a function of depth and wavelength.
AB  - PURPOSE: To determine quantitatively dependence on the wavelength and angle, as a
      function of depth, of light scattering in the human lens. To compare the result
      for forward directions with psychophysical data. To derive candidate particle
      distributions that might be responsible for nuclear light scattering as
      significant in the psychophysical situation. METHODS: The amount of light
      scattered by donor lenses (n = 15, ages 48 to 82 years) from a 1-mm x 0.1-mm
      white slit beam was measured as a function of depth in the lens for seven angles
      from 10 degrees to 165 degrees, and for four wavelengths from 400 to 700 nm.
      Absolute values for light scattering (Rayleigh ratios) were derived. RESULTS: The
      light-scattering data are confounded by the short wavelength-absorbing pigments
      in the lens. After correction, backward light scattering in the nucleus followed
      wavelength to a power of -4. In the superior layers and for forward directions in
      the nucleus, light scattering was less dependent on wavelength. The nuclear data
      could be explained on the basis of a bimodal protein particle distribution:
      particles much smaller than wavelength, in quantitative accordance with the
      literature, and particles larger than wavelength, which control forward light
      scattering. CONCLUSIONS: The particles of significance for forward light
      scattering have, on average, a mean radius of 692 nm and constitute only 0.000003
      of the volume. The wavelength dependence of retinal stray light is lessened by:
      the large sizes, the contribution of superficial lenticular layers, the
      lenticular pigments, and the contribution of other components of the eye.

PMID- 9191596
TI  - Peroxynitrite and oxidative damage in experimental autoimmune uveitis.
AB  - PURPOSE: Results of a previous study demonstrated the presence of superoxide and
      nitric oxide in experimental autoimmune uveitis (EAU). These two chemical
      entities have recently been shown to combine rapidly to form one of the most
      potent known biologic oxidants, peroxynitrite. As an extension of the previous
      study, the current study was proposed to determine whether peroxynitrite is
      generated in EAU and the site and extent of any oxidative damage thereby
      inflicted. METHODS: Experimental uveitis was induced in Lewis rats with retinal S
      antigen. The localization of peroxynitrite was carried out by immunohistochemical
      detection of its nitration product, nitrotyrosine, using polyclonal rabbit
      antinitrotyrosine antibody. The lipid peroxides in the membrane were detected by
      fluorescent labeling of their secondary carbonyl products with 3-hydroxy-2
      naphthoic acid hydrazide. This fluorescent product was also visualized by
      coupling with Fast Blue B. A confocal laser scanning microscope was used for
      detection. RESULTS: In EAU, the peroxynitrite plaques were observed to
      concentrate in the photoreceptors but were also visible in some inner retinal
      areas, including ganglion cell layers, nerve fiber layers, and retinal blood
      vessels. The lipid peroxides were localized exclusively in the photoreceptors,
      concentrating in the vicinity of the infiltrating phagocytes but not localized on
      the phagocytic cells themselves. Similar peroxide lesions in the photoreceptors
      were also generated by aerobically exposing the naive, open eyecups to a radical
      generator, 2,2'azobis(2-amidinopropane) hydrochloride. CONCLUSIONS: In EAU, there
      was a substantial concentration of peroxynitrite in the photoreceptors. The
      presence of this oxidant appears to correlate with the pathologic oxidation
      demonstrated in this area. The photoreceptors are especially prone to radical
      induced lipid peroxidation caused by the high concentration of docasahexaenoic
      acid that is contained in these structures.

PMID- 9191597
TI  - Effect of synthetic metalloproteinase inhibitor or citrate on neutrophil
      chemotaxis and the respiratory burst.
AB  - PURPOSE: A topical synthetic metalloproteinase inhibitor (SIMP) has been reported
      to reduce the incidence of corneal ulcerations in the alkali-injured eye by the
      putative mechanism of collagenase inhibition. The current study was performed to
      determine whether SIMP has a direct inhibitory effect on the activation of
      neutrophils and to compare any such effect with that of citrate, a known
      inhibitor of polymorphonuclear leukocyte (PMNL) activity. METHODS: The effect of
      SIMP or citrate was tested on chemotaxis of PMNL and the respiratory burst in
      vitro. RESULTS: Synthetic metalloproteinase inhibitor (1 mM) or citrate (12 mM)
      produced significant inhibition of chemotaxis of PMNL and the accompanying
      behavioral characteristics of motility. Synthetic metalloproteinase inhibitor,
      but not citrate, generated a dramatic respiratory burst when incubated with
      resting PMNL. Both SIMP and citrate inhibited the respiratory burst of PMNL in
      the presence of opsonized zymosan. For a brief, initial period each substance
      enhanced the respiratory burst generated by the metabolic stimulant from alkali
      degraded corneas, followed by a rapid decline in activity that was associated
      with cell death. CONCLUSIONS: Although SIMP has been shown to exhibit powerful
      collagenase inhibition, its inhibitory effect on chemotaxis of PMNL might be the
      primary mechanism in reducing the incidence of ulceration in the alkali-injured
      cornea. Very significant reduction in the accumulation of PMNL in SIMP-treated
      corneas supports this conviction. Activation by SIMP of the respiratory burst in
      resting PMNL is of concern, but overall its beneficial effect is favorable, as
      demonstrated in prior alkali-injured animal models. The dual effect of inhibition
      of chemotaxis of PMNL and activity of collagenase makes SIMP a potential drug for
      combating ulceration in the alkali-injured cornea.

PMID- 9191598
TI  - Characterization of cytokine mRNA transcripts in conjunctival cells in patients
      with allergic conjunctivitis.
AB  - PURPOSE: The host response to allergens appears to be regulated by specific
      patterns of local cytokine production. More than 20,000 conjunctival superficial
      cells were collected with a special brush, a smaller version of the Cytobrush
      used in cervical cytology, from the upper palpebral conjuntiva. METHODS: Samples
      were obtained by cytology brush from seven patients with allergic conjunctivitis
      and from seven healthy volunteers. Giemsa staining, immunocytochemistry, and flow
      cytometric analysis were performed. Cytokine gene expression was assayed by the
      reverse-transcription-polymerase chain reaction method. RESULTS: Giemsa staining
      of cytocentrifuged preparations from patients with allergic conjunctivitis showed
      conjunctival epithelial cells with lymphocytes, mast cells, and eosinophils. In
      an immunohistochemical study, a few CD3- and CD4-bearing cells, but not CD20- and
      CD14-bearing cells, were seen in patients. In 82.6 +/- 17% of the samples
      obtained from allergic patients, HLA-DR was present, but it was present in only
      34.2 +/- 17.8% of samples from control subjects (P = 0.0001) using flow
      cytometric analysis. Steady state transcripts of mRNA for cytokines were analyzed
      with RT-PCR in conjunctival cell samples, and results showed that samples from
      allergic conjunctivitis expressed increased transcripts of interleukin 4 and
      interleukin 13 but virtually no interleukin 2 or interferon-gamma; six samples
      from seven healthy subjects expressed no interleukin 2, interleukin 4,
      interleukin 13, or interferon-gamma transcripts. CONCLUSIONS: These results
      suggest that the clinical features of allergic conjunctivitis in humans are
      associated with a specific local pattern of proinflammatory cytokine expression.

PMID- 9191599
TI  - Induction of basic fibroblast growth factor mRNA by basic fibroblast growth
      factor in Muller cells.
AB  - PURPOSE: To investigate the induction of basic fibroblast growth factor (bFGF)
      gene expression in cultured rat Muller cells by bFGF and to study the mechanism
      of induction. METHODS: Muller cells from 1- to 3-day-old Sprague-Dawley rats were
      isolated and cultured with Dulbecco's modified Eagle's medium with 10% fetal calf
      serum. Cultured cells were identified by immunocytochemistry using antibodies
      against vimentin, carbonic anhydrase II, and glutamine synthetase. Cells of
      passages 1 through 4 were treated with bFGF, the protein kinase C (PKC)
      inhibitor, H-7; calphostin C, or the PKC activator, PMA; and protein kinase A
      (PKA) inhibitor, H-89; as well as the adenylate cylase activator, forskolin; or
      the adenylate cyclase inhibitor, SQ22536. Northern blot analysis was performed to
      determine the mRNA expression of bFGF, ciliary neurotrophic factor (CNTF) and
      brain-derived neurotrophic factor (BDNF). RESULTS: Addition of bFGF to culture
      medium induced bFGF gene expression in a dose- and time-dependent manner.
      Induction of bFCF mRNA started at a bFGF concentration of 0.1 ng/ml. The bFGF
      mRNA level was elevated by 2-fold at 1 ng/ml of bFGF, 2.8-fold at 5 ng/ml, and
      reached a peak of 4-fold at 10 ng/ml and 3.7-fold at 50 ng/ml. At 10 ng/ml of
      bFGF, induction of bFGF mRNA was observed as early as 2 hours (2-fold) after
      treatment. The bFGF mRNA level continued to increase to 3.7-fold by 4 hours, and
      reached a maximum of 4.4-fold by 8 hours. A slow decline of the bFGF mRNA level
      was observed after 8 hours of bFGF treatment (3.5-fold by 12 hours, and 3-fold by
      24 hours). This induction of bFGF gene expression was blocked by PKC inhibitors H
      7 (30 microM). The PKC activator PMA (0.1 microM) also upregulated bFGF gene
      expression, but the effects of bFGF and PMA were not additive. An adenylate
      cyclase inhibitor, SQ22536 (100 microM), did not inhibit bFGF-induced bFGF gene
      expression. Although forskolin (5 microM), an adenylate cyclase activator, also
      upregulated the level of bFGF mRNA, the effects of forskolin and bFGF were
      additive. In addition, no inhibitory effect on bFGF-induced expression of bFGF
      mRNA was found using H-89 (1 microM). Exogenous bFGF did not alter the mRNA
      levels of CNTF and BDNF. CONCLUSIONS: These results indicate that bFGF induces
      bFGF gene expression in cultured rat Muller cells through PKC activation. The
      authors' findings raise the possibility that Muller cells in vivo also respond to
      available bFGF (for example, that released from the endogenous reservoirs in the
      case of injury) or to exogenous bFGF by producing more bFGF, which could in turn
      promote photoreceptor survival.

PMID- 9191601
TI  - MK-801 has neuroprotective and antiproliferative effects in retinal laser injury.
AB  - PURPOSE: Treatment of the retina by laser photocoagulation often is complicated
      by an immediate side effect of visual impairment, caused by unavoidable, laser
      induced destruction of healthy tissue adjacent to the lesion. A neuroprotective
      therapy that salvages this healthy tissue might enhance the benefit obtained from
      the treatment. This study was proposed to determine whether glutamate-receptor
      blockers can provide adjuvant neuroprotection during laser photocoagulation. The
      effect of MK-801, an NMDA-receptor antagonist, on laser-induced retinal injury
      was examined, in a rat model. METHODS: Argon laser lesions were created in the
      retinas of 36 DA rats, and were followed immediately by intraperitoneal
      injections of MK-801 (2 mg/kg) or saline. The animals were killed after 3, 20, or
      60 days and the retinal lesions were evaluated histologically and
      morphometrically. RESULTS: Photoreceptor-cell loss was significantly less in MK
      801-treated rats than in control animals. The proliferative membrane composed of
      retinal pigment epithelial cells and neovascular blood vessels, which was seen at
      the base of the lesion in control group retinas, was smaller in the MK-801
      treated retinas. In rats treated with a higher dose of MK-801, the lesions showed
      almost no proliferative reaction. CONCLUSIONS: A potent noncompetitive NMDA
      receptor blocker, MK-801 exhibits neuroprotective and antiproliferative
      properties in the retina. Glutamate-receptor blockers should be investigated
      further as potential adjuvant therapy in retinal photocoagulation treatments.

PMID- 9191600
TI  - Repair phenotype in corneal fibroblasts is controlled by an interleukin-1 alpha
      autocrine feedback loop.
AB  - PURPOSE: To explore the role of autocrine interleukin-1 alpha (IL-1 alpha) as a
      central regulator of the repair phenotype in corneal fibroblasts. METHODS:
      Disruption of the actin cytoskeleton with cytochalasin B (CB), which mimics
      changes in shape that occur in repair tissues, was used to stimulate repair gene
      expression in early-passage fibroblasts. Changes in expression of IL-1 alpha, IL
      8, collagenase, and ENA-78 were determined by Northern blot analysis,
      radioimmunoassay, and an enzyme-amplified sensitivity immunoassay (EASIA).
      Expression of repair genes was also examined in repair fibroblasts, isolated from
      healing, penetrating keratectomy wounds in rabbits. RESULTS: Blocking IL-1 alpha
      activity prevented both constitutive and stimulated increases in synthesis of IL
      8 and collagenase in early-passage cultures of corneal fibroblasts, demonstrating
      the role of IL-1 alpha as a necessary intermediate for expression of these genes.
      Evidence is also presented that the IL-1 alpha autocrine controls expression of
      an IL-8 related factor, ENA-78. Unlike early-passage fibroblasts, fibroblasts
      freshly isolated from the uninjured cornea did not express IL-1 alpha. However,
      fibroblasts freshly isolated from remodeling corneal repair tissue 3 weeks after
      injury were found to express substantial levels of IL-1 alpha, regulated through
      an autocrine feedback loop. Neutralization experiments demonstrated that the IL-1
      alpha autocrine is largely responsible for controlling both collagenase and IL-8
      synthesis in repair fibroblasts, as it is in early-passage fibroblasts.
      CONCLUSIONS: These findings provide evidence that activation of an autocrine IL-1
      alpha feedback loop is an important mechanism by which fibroblasts adopt a repair
      phenotype during remodeling of the cornea.

PMID- 9191603
TI  - The role of Schwann cells during retinal ganglion cell regeneration induced by
      peripheral nerve transplantation.
AB  - PURPOSE: To investigate the key role of Schwann cells in retinal ganglion cell
      regeneration elicited by peripheral nerve autotransplantation. METHODS: Three
      kinds of autografts, Schwann-cell graft (intact sciatic nerve, consisting of
      living Schwann cells and their basal laminae). Schwann-cell-eliminated graft
      (consisting mainly of Schwann cell basal laminae) and partial Schwann-cell graft
      (consisting of basal laminae and diffusible factors secreted by Schwann cells)
      were prepared and autotransplanted to the adult rat optic nerve. The membrane
      specialization between regenerating axons and Schwann cells was observed by
      electron microscopy. The expression of cell adhesion molecules was demonstrated
      by Western blot analysis and immunohistochemistry. RESULTS: Retinal ganglion cell
      axons were observed to regenerate into the Schwann-cell graft in contact with
      Schwann cells but not into the Schwann-cell-eliminated graft. The regeneration
      was not observed in the empty basal laminae of the partial Schwann-cell graft.
      Most of regenerating axons contacted astrocytes in the optic nerve segment, and
      Schwann cells in the graft. At the interface of regenerating axon and Schwann
      cell, in addition to immunoreactivity of N-CAM and LI, short focal tight
      junctions were observed. CONCLUSIONS: These results suggested that viable Schwann
      cells are good substrate for retinal ganglion cell regeneration, the intimate
      contact with viable Schwann cell surface plays an important role in retinal
      ganglion cell regeneration, tight junctions, and cell adhesion molecules (LI, N
      CAM) are observed between the regenerating axon and Schwann cell.

PMID- 9191602
TI  - Induction of apoptosis in cultured human retinal pigment epithelial cells is
      counteracted by flupirtine.
AB  - PURPOSE: The aim of the study was to determine whether flupirtine can counteract
      the induction of apoptosis in cultured retinal pigment epithelium (RPE) cells.
      METHODS: Confluent cultures were subjected to experimental ischemia (medium free
      of serum, glucose, and oxygen) with or without various substances for specific
      periods. The cells were then examined for breakdown of DNA by the TUNEL procedure
      and agarose gel electrophoresis. Moreover cells were processed for the
      localization of oncogene proteins (bcl-2, TIAR, ICH-1t) associated with
      apoptosis. The effect of flupirtine on reactive oxygen species also was
      determined. RESULTS: When RPE cells were subjected to ischemia for 72 hours
      approximately 65% of cells remained attached to the coverslips and approximately
      65% of their nuclei showed clear fragmentation of DNA by TUNEL. Most of the cells
      exhibited a shrunken appearance typical of apoptosis. Fragmentation of the DNA
      from cells given ischemia for 72 hours was also confirmed by agarose gel
      electrophoresis. Inclusion of flupirtine (flupirtine gluconate, 100 microM) or
      10% fetal calf serum in the medium prevented ischemia-induced apoptosis occurring
      after 72 hours. Neither N-methyl-D-aspartate (NMDA) (100 microM) nondeferoxamine
      (100 microM) nor the NMDA antagonists dextromethorphan (100 microM), memantine
      (100 microM), and MK-801 (10 microM) had a similar effect. NMDA, and to a lesser
      extent memantine, induced apoptosis independently. Treatment of RPE cells in
      serum-free medium with flupirtine (flupirtine gluconate, 100 microM) for 72 hours
      caused an upregulation of bcl-2 protein. In contrast, the oncogene proteins for
      TIAR and ICH-1t, were lower in flupirtine-treated cells than in control cells.
      Flupirtine, like deferoxamine, prevents iron-ascorbate-induced reactive oxygen
      species formation in retinal cells, but only flupirtine prevents ischemia-induced
      apoptosis in RPE cells. CONCLUSIONS: The combined data demonstrate that
      flupirtine is an effective agent in preventing death by apoptosis. Flupirtine
      reduces formation of reactive oxygen species in retinal dissociates and causes
      changes in various oncogene products in RPE cultures, which may explain its
      action in preventing apoptosis induced by ischemia. The current results also
      suggest that NMDA receptors are not involved in the induction of ischemia-induced
      apoptosis in RPE, cells.

PMID- 9191604
TI  - Systemic cytokine immunotherapy for experimental cytomegalovirus retinitis in
      mice with retrovirus-induced immunodeficiency.
AB  - PURPOSE: To evaluate and compare the in vivo administration of interleukin-2 (IL
      2) or interleukin-12 (IL-12) in the immunotherapy of necrotizing retinitis caused
      by murine cytomegalovirus (MCMV) in mice with a retrovirus-induced
      immunodeficiency syndrome (MAIDS). METHODS: Adult C57BL/6 mice with MAIDS of 8
      weeks' duration were treated with either a single intramuscular injection of
      polyethylene glycol-modified human recombinant IL-2 (PEG-IL-2) or multiple
      intramuscular injections of murine recombinant IL-12; untreated mice with MAIDS
      received phosphate-buffered saline. Two days later, the left eyes of all mice
      were inoculated with MCMV by subretinal injection and evaluated at day 6 for
      intraocular MCMV titers or at day 10 for frequency of necrotizing MCMV retinitis.
      RESULTS: Infectious MCMV was significantly reduced in whole eyes of PEG-IL-2
      treated mice with MAIDS (2.8 log10), but not in whole eyes of IL-12-treated
      animals (4.4 log10) when compared with whole eyes of untreated animals with MAIDS
      (4.5 log10). Similarly, whereas eyes from approximately 80% of IL-12-treated and
      untreated mice with MAIDS showed histopathologic features consistent with classic
      necrotizing MCMV retinitis (full-thickness retinal necrosis associated with virus
      inclusions and cytomegalocytes), none (0%) of PEG-IL-2-treated animals with MAIDS
      showed classic MCMV retinitis. Instead, eyes from these animals showed either
      retinal folding or outer retinal atrophy, a pattern of histopathology similar to
      that observed in eyes from immunologically normal C57BL/6 mice inoculated
      subretinally with MCMV. CONCLUSIONS: These results provide proof-of-principle for
      the hypothesis that systemic cytokine immunotherapy will reduce the frequency of
      CMV retinitis in a setting of retrovirus-induced immunosuppression. Because of
      the striking differential effects of IL-2 and IL-12 on MCMV-retinitis in mice
      with MAIDS, the authors conclude that cytokine immunotherapy for cytomegalovirus
      induced retinitis is cytokine-specific, even for such cytokines as IL-2 and IL-12
      that have T cell regulation in common.

PMID- 9191605
TI  - Prophylactic and therapeutic efficacy of immunoglobulin G antibodies to
      Pseudomonas aeruginosa lipopolysaccharide against murine experimental corneal
      infection.
AB  - PURPOSE: To evaluate the efficacy of lipopolysaccharide (LPS)-specific antibodies
      administered prophylactically or therapeutically to protect against corneal
      challenge with Pseudomonas aeruginosa. METHODS: The prophylactic efficacy of
      active immunization with purified P. aeruginosa LPS was evaluated in a murine
      corneal-scratch model of P. aeruginosa keratitis. The same model was used to
      evaluate both the prophylactic and the therapeutic efficacy of systemic passive
      transfer of variable region-identical, isotype-switched, LPS-specific, murine
      immunoglobulin M (IgM) and immunoglobulin G (IgG) monoclonal antibodies (mAbs).
      The mAbs were injected intraperitoneally at various times either before or after
      corneal challenge and the corneal response was monitored macroscopically. In
      addition, immune rabbit sera were used to evaluate the efficacy of treatment.
      RESULTS: Active immunization with homologous, but not heterologous, LPS before
      challenge reduced the severity of corneal disease and protected challenged mice
      against permanent corneal damage. Passive transfer of the LPS-specific IgM mAb
      1F6 before challenge did not prevent corneal damage at any dose tested and had no
      effect on the course of disease. However, results of dose-response studies of the
      passive transfer of a variable region-identical IgG2b mAb, 2H3, before challenge
      indicated a 50% protective dose of 11.8 micrograms. When mAb 2H3 was administered
      at a dose of 50 micrograms before challenge and the challenge inoculum was
      increased, all mice were protected from corneal damage up to a challenge inoculum
      of 2.2 x 10(8) CFU/eye. When given 2 or 4 hours after corneal challenge with P.
      aeruginosa strain 6294 (which invades corneal epithelial cells during infection)
      but not when given at 8 or 24 hours, 50 micrograms of mAb 2H3 conferred
      significant protection (P < 0.05). The maximal interval after challenge during
      which this antibody could be administered and still protect 50% of mice was
      calculated by probit analysis to be 9.4 hours. Administration of homologous LPS
      specific rabbit antiserum to mice at various times after challenge with P.
      aeruginosa strain 6206 (which is cytotoxic to corneal epithelial cells and does
      not remain in these cells during infection) resulted in significant protection
      when administered 4 or 8 hours after infection. Although probit analysis could
      not be performed with the available data, 50% of mice were completely protected
      when the antiserum was given up to 24 hours after challenge. CONCLUSIONS: In an
      experimental model of P. aeruginosa keratitis, systematically delivered IgG
      antibodies directed against the O-side-chain antigens of P. aeruginosa, LPS
      conferred protection against severe corneal damage when administered both
      prophylactically and therapeutically.

PMID- 9191606
TI  - The HNK-1 epitope and the elastic fiber system of the human ciliary body. An
      immunoelectron microscopic study.
AB  - PURPOSE: To localize at the electron microscopic level the cell adhesion-related
      HNK-1 carbohydrate epitope in the inner connective tissue layer (ICTL) of the
      human ciliary body. METHODS: Seven specimens representing the pars plicata (age
      range, 12 to 86 years) and three specimens representing the pars plana (age
      range, 29 to 71 years) of the ciliary body were sampled at death from eight
      normal human eyes. Three additional specimens from the pars plicata were taken
      from three eyes with exfoliation syndrome (age range, 78 to 81 years). All
      specimens were embedded in LR white resin and studied by postembedding immunogold
      labeling using two monoclonal antibodies (mAbs) HNK-1 and NC-1 in detecting the
      HNK-1 epitope. RESULTS: In the ICTL of the pars plicata and the pars plana, mAbs
      HNK-1 and NC-1 constantly bound to the surface of fibroblast-like cells present
      in the subepithelial connective tissue matrix. The immunoreaction was localized
      along the cell membrane, both around the cell body and around its long, slender
      cytoplasmic processes. Long microfibrillar bundles, which consisted of
      approximately 10-nm thick microfibrils in close association with these
      subepithelial matrix cells and elastic fibers, were also labeled. The periphery
      of elastic fibers was likewise immunolabeled for the HNK-1 epitope. The reaction
      pattern was essentially the same, regardless of age and presence or absence of
      exfoliation syndrome. CONCLUSIONS: At the ultrastructural level, the HNK-1
      epitope in the ICTL is a common denominator to the subepithelial matrix cells,
      microfibrillar bundles, and elastic fibers. This suggests that the subepithelial
      matrix cells secrete this epitope, and that molecules hearing it may be involved
      in joining these connective tissue elements that structurally stabilize the
      ciliary body.

PMID- 9191607
TI  - Muscarinic receptor subtypes in human iris-ciliary body measured by
      immunoprecipitation.
AB  - PURPOSE: To determine the relative levels of the five muscarinic receptor
      subtypes in the anterior segment of the human eye. METHODS: Antisera selective
      for each of the five muscarinic receptor proteins were incubated with [3H]-QNB
      bound receptors solubilized from human iris sphincter, ciliary muscle, and
      ciliary processes. Precipitation of the radiolabeled receptor-antibody complexes
      and scintillation counting enabled quantitation of the subtypes in the various
      tissues. Reverse transcription-polymerase chain reaction was performed on the
      tissues and cultured smooth muscle cells derived from them. RESULTS:
      Approximately 60% to 75% of the muscarinic receptors in the human iris sphincter
      and ciliary body are the m3 subtype. Lower levels (5% to 10%) of the m2 and m4
      receptors are present in these tissues. The m1 receptor (7%) was detected in the
      ciliary processes and iris sphincter and the m5 receptor (5%), which is usually
      found only in the central nervous system, was present in the iris sphincter.
      CONCLUSIONS: The m3 subtype is the predominant muscarinic receptor in the
      anterior segment of the human eye. The extensive heterogeneity of muscarinic
      receptors makes it difficult to predict whether subtype-selective drugs will have
      an improved efficacy and side-effect profile.

PMID- 9191608
TI  - Foveal cone function in nonproliferative diabetic retinopathy and macular edema.
AB  - PURPOSE: To study results of foveal cone electroretinography (ERG) in patients
      with nonproliferative diabetic retinopathy (NPDR), with and without clinically
      significant macular edema (CSME). METHODS: Electroretinograms of foveal cones
      were elicited, with a dual-beam stimulator-ophthalmoscope, from 18 consecutive
      patients with bilateral NPDR and unilateral CSME. RESULTS: Analysis of resulting
      data revealed that mean amplitude was significantly lower in eyes with CSME and
      in eyes without CSME., compared with that in normal eyes. Mean implicit time was
      significantly longer in eyes with CSME compared with that in normal eyes, but in
      eyes of diabetic patients without CSME., mean implicit time was the same as that
      in normal eyes. Amplitudes were directly correlated and implicit times were
      inversely correlated with best-corrected Snellen visual acuity in eyes with and
      without CSME. Eyes with CSME had significantly lower amplitudes and longer
      implicit times than their fellow eyes without CSME. In addition, eyes with NPDR,
      with or without CSME, did not exhibit the normal rise in amplitude with
      increasing duration of light exposure. CONCLUSIONS: Electroretinographic findings
      showed abnormalities in foveal cone responses in eyes with NPDR, particularly in
      the presence of CSME. These results may support a functional role for outer
      retinal dysfunction in patients with diabetic retinopathy and loss of central
      vision.

PMID- 9191609
TI  - Decreased nitric oxide production accounts for secondary arteriolar constriction
      after retinal branch vein occlusion.
AB  - PURPOSE: After retinal branch vein occlusion (BVO), the arteriole crossing the
      occluded territories is often constricted. This constriction persists up to
      several weeks and is correlated with the development of extended territories of
      nonperfused capillaries. These are results of an investigation supporting the
      hypothesis that decrease in the production of nitric oxide (NO) accounts for the
      observed arteriolar constriction. METHODS: Preretinal [NO] was measured using an
      NO microprobe in the anesthetized miniature pigs, before and during the first 4
      hours after experimental branch vein occlusion. Modifications of arteriolar
      diameter were correlated to preretinal [NO] changes. The retinal arteriolar
      sensitivity to constitutive NO was checked by applying preretinal puff injections
      of nitro-L-arginine (L-NA) after both systemic hypoxia and branch vein occlusion.
      RESULTS: Two hours after branch vein occlusion there was a 73.7 +/- 4% decrease
      in preretinal [NO] and a simultaneous 25.4 +/- 3.4% decrease in the diameter of
      the arteriole in the affected territory. Both persisted for at least 4 hours
      after branch vein occlusion. Applying a puff of L-NA to an arteriole previously
      dilated by systemic hypoxia induced a vasoconstriction. However, no arteriolar
      constriction was observed when a puff was applied to an arteriole after branch
      vein occlusion. CONCLUSIONS: These results show that experimental branch vein
      occlusion induces in the affected retina an impairment in the release of
      constitutive NO and an arteriolar constriction, which, in turn, contributes to
      the development of hypoxia in tissue and neuronal swelling and death in the inner
      retina.

PMID- 9191610
TI  - Flow cytometry in impression cytology specimens. A new method for evaluation of
      conjunctival inflammation.
AB  - PURPOSE: To investigate feasibility and potential uses of flow cytometry in
      impression cytology as a new procedure to assess and quantify conjunctival
      inflammation. METHODS: Specimens for cytology were collected by impression from
      30 patients with various chronic ocular surface disorders and from 10 normal
      subjects. Two specimens were obtained in each eye: One was transferred onto a
      glass slide and processed by immunofluorescence with antibodies to human
      leukocyte antigen (HLA)-DR antigens; cells from the other were suspended in
      phosphate-buffered saline for flow cytometry. Monoclonal antibodies to HLA-DR
      antigens and CD23, the low affinity receptor to immunoglobulin E, were used.
      RESULTS: Abnormal expression of HLA-DR and CD23 by conjunctival cells was found
      in 13 of 18 dry eyes and in 20 of 22 eyes with chronic conjunctivitis, whereas
      specimens remained almost negative (less than 10% of cells were positive) in
      normal eyes. Percentages of positive cells ranged between 20% and 98% of all
      conjunctival cells. Correlation between the two methods, immunocytology and flow
      cytometry, was highly significant (coefficient of correlation 0.77, P = 0.0001).
      Moreover, HLA-DR positivity, at its strongest intensity, was observed in a
      minority of cells (1% to 12%), most of which were resident class II-expressing
      dendritic cells. Percentages of those cells expressing high levels of HLA-DR were
      3 +/- 1.2% in normal eyes, 5.8 +/- 4% in dry eyes (P = 0.05), and 5.9 +/- 3.5% in
      eyes with chronic conjunctivitis (P = 0.02). CONCLUSIONS: Results of this
      preliminary study confirm that conjunctival epithelial cells may abnormally
      express inflammatory markers in chronic ocular surface disorders. Development of
      flow cytometry in analysis of cytologic specimens provides a new, sensitive, and
      objective tool for exploring conjunctival pathology.

PMID- 9191611
TI  - The other side of the bed.

PMID- 9191612
TI  - Attitudes toward treating depression.

PMID- 9191613
TI  - Cost-effectiveness analysis.

PMID- 9191614
TI  - Cost-effectiveness analysis.

PMID- 9191615
TI  - Prayer in office practice.

PMID- 9191616
TI  - Bypass surgery vs angioplasty in multivessel CAD.

PMID- 9191617
TI  - Treatment of dysthymia.

PMID- 9191618
TI  - Maternal fever after epidural analgesia.

PMID- 9191619
TI  - Safety and efficacy of first-line antihypertensives.

PMID- 9191620
TI  - Serious bacterial infection in children.

PMID- 9191621
TI  - Perioperative steroids for secondary adrenal insufficiency.

PMID- 9191622
TI  - Propionyl-L-carnitine for intermittent claudication.

PMID- 9191623
TI  - Carotid endarterectomy without arteriography.

PMID- 9191624
TI  - Intrathecal analgesia for labor.
AB  - Intrathecal analgesia is a highly effective technique for pain relief in the
      first stage of labor. It is a technically simple procedure that can be easily
      learned by family physicians currently performing diagnostic lumbar puncture. Its
      effectiveness, simplicity, and low incidence of serious complications make it
      especially applicable to the practices of physicians delivering babies in areas
      where continuous epidural anesthesia is not available. This article describes the
      procedure of intrathecal analgesia, and discusses advantages, complications, side
      effects, and applications.

PMID- 9191625
TI  - Do cost-effectiveness analyses cause you dyspepsia?

PMID- 9191626
TI  - Between research and practice in family medicine: the gulf resolution.

PMID- 9191627
TI  - Evaluation of the dyspeptic patient: a cost-utility study.
AB  - BACKGROUND: Traditionally, patients presenting with uncomplicated dyspepsia have
      been managed using empiric antisecretory therapy, followed by endoscopy in the
      event of persistent symptoms or complication. Since Helicobacter pylori is now
      accepted as an important and potentially reversible cause of ulcer disease, it is
      important to reevaluate the management of dyspepsia. The goal of this study is to
      evaluate seven outpatient strategies for the management of dyspeptic patients
      using a cost-utility analysis. METHODS: The study design was that of a cost
      utility analysis. The model assumes that an adult patient with signs of dyspepsia
      but no signs of complication presents to the outpatient office of a primary care
      physician. Seven strategies are modeled: empiric antisecretory therapy; empiric H
      pylori eradication using oral omeprazole (20 mg [corrected] twice daily),
      clarithromycin (500 mg twice daily), and amoxicillin (1000 mg twice daily); use
      of either upper endoscopy, an upper gastrointestinal barium study (an upper GI),
      or the serum titer for H pylori as a diagnostic test to identify patients for H
      pylori eradication; or use of an initial diagnostic test followed by the serum
      titer for H pylori. The primary outcome was the cost per quality-adjusted life
      year (QALY) for each strategy for a 1-year period from presentation; secondary
      outcomes included the probability of symptomatic ulcer recurrence, cost per ulcer
      cure, and mortality. RESULTS: Three strategies were similarly cost-effective:
      empiric H pylori eradication ($1198 per QALY), use of a serum H pylori titer as
      an initial diagnostic test ($1214 per QALY), and empiric antisecretory therapy
      ($1288 per QALY). Empiric antisecretory therapy, however, was associated with
      significantly more symptomatic ulcer recurrences and deaths than any other
      strategy. CONCLUSIONS: This cost-utility analysis suggests that two strategies
      are reasonable for patients presenting with dyspepsia: (1) empiric H pylori
      eradication and (2) use of a serum H pylori titer to identify patients who might
      benefit from H pylori eradication. The latter strategy may be preferable because
      it is less likely to lead to antibiotic resistance. Strategies utilizing an upper
      GI or upper endoscopy (either with or without serum H pylori titer) or empiric
      antisecretory therapy do not improve outcomes and are associated with greater
      cost, morbidity, and/or mortality.

PMID- 9191628
TI  - Do low-risk prenatal patients really need a screening glucose challenge test?
AB  - BACKGROUND: It is common practice to routinely screen pregnant women for
      gestational diabetes. The screening technique typically used is the 1-hour 50-g
      oral glucose tolerance test (OGTT), with a subsequent 3-hour 100-g OGTT for women
      whose 1-hour test was positive. This process can be both time-consuming and
      inconvenient for patients. Additionally, its sensitivity and specificity are
      estimated to be 70% and 87% respectively, and data about the effect of screening
      and treatment on low-risk pregnancy outcomes are limited. The objective of this
      study was to reassess the value of routine screening of all pregnant patients
      with a 1-hour glucose challenge test. METHODS: At a university-based family
      practice center with a predominantly low-risk population, a retrospective
      analysis was performed of all patients (n = 595) who received prenatal care and
      gave birth between January 1988 and December 1993. Among women in whom
      gestational diabetes was diagnosed on the basis of glucose tolerance testing, we
      identified those with risk factors for the disease, and examined whether a
      selective screening program based on risk factors alone would have resulted in
      correct diagnoses of gestational diabetes. RESULTS: Of the 595 patients, 544
      (91.4%) were screened with a 1-hour 50-g OGTT. This initial screening test was
      positive in 76 women (12.8%). Of these, 58 (76.3%) then had a 3-hour 100-g OGTT,
      and 13 received a diagnosis of gestational diabetes. Nine of these 13 women had
      risk factors for gestational diabetes. We determined that less than 1% of
      prenatal patients without risk factors for gestational diabetes were ultimately
      found to have gestational diabetes. CONCLUSIONS: Screening with a 1-hour 50-g
      OGTT only those women who have identifiable risk factors for gestational diabetes
      is a reasonable approach to identifying the disease in a low-risk population. All
      pregnant women should have a thorough history taken to determine whether they
      have risk factors for gestational diabetes.

PMID- 9191630
TI  - Evaluation and treatment of respiratory infections: does managed care make a
      difference?
AB  - BACKGROUND: Primary care physicians frequently use antibiotics for nonindicated
      conditions and conditions for which antibiotics have not been shown to be
      effective. The intention of this study was to determine whether shifting the
      costs from the insurer to physicians in a staff model health maintenance
      organization (HMO) influenced antibiotic prescribing. METHODS: A random sample of
      patients in whom upper respiratory infections (URIs) (n = 334) or acute
      bronchitis (n = 218) were diagnosed within a 12-month period was selected from a
      large multispecialty group practice whose population was predominantly fee-for
      service (FFS) and from a staff model HMO. Detailed chart reviews were performed
      to verify the diagnosis and note secondary diagnoses, identify whether an
      antibiotic or other medication was prescribed, assess whether diagnostic testing
      was performed, and determine the specialty of the clinician. RESULTS: After
      excluding patients seen with sinusitis, otitis media, or streptococcal
      pharyngitis, 334 patients with URIs and 218 patients with acute bronchitis
      remained for analysis. For URIs, antibiotic prescribing was higher in the HMO
      population than in the FFS group (31% vs 20%, P = .02). In patients with acute
      bronchitis, HMO patients were also more likely to have an antibiotic prescribed,
      but the difference was not statistically significant (82% vs 73%, P = .11).
      Further analyses showed that while HMO physicians were more likely to prescribe
      antibiotics, they were less likely to prescribe other medications for acute
      bronchitis or use diagnostic tests for evaluation of patients with URIs or
      bronchitis. CONCLUSIONS: Shifting costs from insurer to physicians through
      managed care appears to reduce diagnostic testing for URIs and acute bronchitis,
      but does not decrease excessive use of antibiotics and may actually increase
      antibiotic use for URIs.

PMID- 9191629
TI  - The education of depressed primary care patients: what do patients think of
      interactive booklets and a video?
AB  - BACKGROUND: Clinicians, policy makers, and health care administrators are
      attempting to improve depression outcomes in the primary care setting. Despite
      positive evidence about the efficacy of self-help materials and psychoeducational
      interventions, use of educational materials designed for the primary care patient
      are receiving little attention in present depression initiatives. The present
      study describes the use and evaluation of three educational materials by
      depressed primary care patients. METHODS: As a part of a randomized control
      trial, depressed primary care patients were identified by primary care physicians
      and randomized to a clinical trial exploring a new method of treating depression.
      Patients assigned to the new method of treatment received a package of
      educational materials at the time of the baseline interview. These materials
      included two brief interactive booklets (medication booklet, behavioral health
      booklet) and a short video. The present analysis concerns data obtained from 108
      intervention patients in a telephone survey conducted 1 week after they received
      the package of educational materials. RESULTS: Approximately three quarters of
      the subjects reported that they read or viewed all of the educational products.
      The majority rated the products as somewhat to significantly helpful: medication
      booklet 81%; behavioral health booklet 82%; and video 69%. Previously reported
      results include findings of significantly better medication adherence and
      improved clinical outcomes by patients with major depression who received a
      primary care intervention that included the educational products discussed in
      this paper. CONCLUSIONS: Educational materials may play a significant role in
      improving depression treatment outcomes in the primary care setting.

PMID- 9191631
TI  - Smoking cessation interventions in rural family practices: an UPRNet study.
AB  - BACKGROUND: Primary care physicians are urged to offer smoking cessation
      counseling to their patients. Many studies have sought to determine which smoking
      interventions are most effective in medical office settings. As a result, routine
      identification of smokers, brief counseling, referral to smoking cessation
      programs, and nicotine replacement therapy are advocated. The context of patient
      visits during which smoking cessation advice is given, however, has received
      little attention. The objective of this study was to determine if patients'
      reasons for visits and self-reported readiness to quit smoking are associated
      with likelihood and type of smoking cessation intervention offered by family
      physicians. METHODS: The study was conducted in the Upper Peninsula Research
      Network (UPRNet), a voluntary association of family physicians in 15 medical
      clinics located in rural areas of northern Michigan. Practice coordinators
      administered a 1-page exit questionnaire to every other adult patient seen by a
      participating physician immediately after the office visit. Clinicians were
      blinded to the specific purpose of the questionnaire. During the study, 2317
      questionnaires were administered, yielding information on 455 smokers. RESULTS:
      The overall rate of physicians' providing any smoking cessation intervention at
      any type of visit was 47%. There was a significant association between frequency
      of smoking cessation intervention and reasons for visits (chi 2 = 10.46, P =
      .01). There was a statistically significant difference between stages of
      readiness to quit and frequency of smoking cessation intervention offered (chi 2
      = 26.5, P < .001). Clinicians offered smoking cessation interventions to smokers
      in the precontemplative stage significantly less often than to smokers in the
      contemplation, preparation, or action stages. CONCLUSIONS: UPRNet practitioners
      vary the frequency of smoking cessation interventions according to patients'
      reasons for the medical visit and their readiness to quit smoking.

PMID- 9191632
TI  - Helping our cause by getting on board.

PMID- 9191633
TI  - Osteoradionecrosis of the jaws: a retrospective study of the background factors
      and treatment in 104 cases.
AB  - PURPOSE: This study analyzed potential risk factors in patients who received
      radiation therapy and then developed osteoradionecrosis (ORN). PATIENTS AND
      METHODS: A group of 104 patients who developed osteoradionecrosis of the jaws
      were reviewed treated between 1972 and 1992. RESULTS: The most common affected
      site was the mandible (99 cases, 95.2%), followed by the maxilla (5 cases, 4.8%).
      Among all cases, 93 (89.4%) were induced-trauma ORN, and 11 (10.6%) were
      spontaneous ORN. The following risk factors were considered as predisposing
      factors for the appearance of ORN: Anatomic location of the tumor, tumor surgery,
      total radiation dose, dose rate/day, mode of radiation delivery, time from
      radiation therapy until the onset of ORN, and dental status. ORN developed more
      frequently with oral cancer than other head and neck cancers. The size of the
      tumor seemed not to influence the incidence of ORN except when the tumor invade
      the adjacent bone. Type of radiation delivery total bone dose, and modes of
      radiation appeared to influence the risk of ORN occurrence. After conservative
      treatment, 44 (42.3%) cases had complete healing and resolution 34 (32.6%) cases
      had a stable, chronic ORN process, and 26 (25.1%) cases had acute and progressive
      ORN. CONCLUSION: An understanding of the risk factors is important in preventing
      ORN after radiation therapy.

PMID- 9191634
TI  - Mandibular metastatic hepatocellular carcinoma: a case involving severe
      postbiopsy hemorrhage.
AB  - PURPOSE: To highlight the hemorrhagic character of metastatic hepatocellular
      carcinoma. PATIENT AND METHOD: A case report of a patient with mandibular
      metastatic hepatocellular carcinoma, who had severe postbiopsy hemorrhagic
      episodes, and literature review is presented. CONCLUSIONS: Mandibular metastatic
      hepatocellular carcinoma is a hemorrhagic tumor because of its hypervascular
      nature. Any rapidly enlarging swelling with ill-defined mandibular destruction
      suggestive of malignancy should be considered for metastatic hepatocellular
      carcinoma. Only a needle biopsy should be attempted in view of the hemorrhagic
      nature of the tumor. Palliative radiotherapy can be useful for the control of
      local expansile symptoms of the tumor and because of its possible role in the
      prevention of hemorrhage.

PMID- 9191635
TI  - Percutaneous injuries during oral and maxillofacial surgery procedures.
AB  - PURPOSE: This study estimated the frequency of percutaneous injuries (Pls) to
      dental health-care workers during oral and maxillofacial surgery and examined the
      circumstances surrounding the incidents. MATERIAL AND METHODS: A self-reported,
      prospective study was conducted to document Pls incurred during oral and
      maxillofacial surgery performed on outpatients and inpatients over 1-month and 6
      month periods, respectively. Among the study variables examined were the numbers
      of patients treated, number and types of procedures performed, duration of
      treatment, numbers and types of health care workers at risk, treatment setting,
      and number of injuries. RESULTS: Four injuries were recorded during 362 operating
      room procedures on 236 inpatients, for a rate of 1.1 Pls per 100 procedures (95%
      confidence interval: 0.3 to 2.8) and 1.7 Pls per 100 patients (95% confidence
      interval: 0.5 to 4.6). These four injuries occurred during 1,665 person
      procedures (mean number of workers present at each procedure times the total
      number of procedures) for a rate of 0.24 Pls per 100 person-procedures (95%
      confidence interval: 0.1 to 1.0). Three injuries took place during fracture
      reductions; two were caused by surgical wire and the third by a needlepoint Bovie
      tip. One injury occurred during orthognathic surgery and involved a Woodson
      elevator. Residents recorded no injuries while treating 521 outpatients (0 Pls
      per 100 patients; 95% confidence interval: 0 to 0.6). CONCLUSION: The results
      support previous findings that Pls rarely occur during outpatients oral and
      maxillofacial surgery procedures. However, the findings suggest that operating
      room procedures for oral and maxillofacial surgery that use wire or involve
      fracture reduction may be associated with an increased risk of injury. Strategies
      such as using a cork or sponge to cap sharp wires or instruments, and protecting
      hands and fingers by double gloving, may be used to decrease the risk of Pl.

PMID- 9191636
TI  - Outpatient orthognathic surgery: review of 205 cases.
AB  - PURPOSE: This article reviews the evolution of outpatient orthognathic surgery
      from 1988 to 1995 at the University of Texas Health Science Center at San
      Antonio. PATIENTS AND METHODS: A total of 328 patients had orthognathic surgery
      from 1988 to 1995. Two hundred and five (124 females, 81 males) were treated on
      an outpatient basis in the surgical suite of the dental school. Procedures
      included bilateral sagittal split osteotomies (BSSO), Le Fort I osteotomies
      (LFI), horizontal mandibular osteotomies (HMO), rapid palatal expansions (RPE),
      and combinations of the above. Additional procedures such as submental
      liposuction, blepharoplasty, dorsoseptorhinoplasty, and otoplasty were performed
      on 22 patients. Patient age ranged from 13 to 64 years, (average age 25).
      RESULTS: Ninety-four (46%) of the patients were discharged the day of surgery.
      One hundred and two (51%) were admitted for 23-hour observation, and five (2.4%)
      were admitted for longer than the 23-hour observation period. Anesthesia time
      over 4:28 significantly correlated with admission for observation status. There
      was no significant difference between LFI and BSSO in relation to admission for
      observation status. CONCLUSIONS: The number and complexity of orthognathic
      procedures increased dramatically over the study period. The length of anesthesia
      time, but not the specific procedure, correlated significantly with admission to
      observation status. There were few unexpected complications, with considerable
      cost reduction and convenience for the patients.

PMID- 9191637
TI  - Public attitudes toward oral surgery: results of a Gallup poll.
AB  - PURPOSE: This article reports the results of a 1994 Gallup survey on public
      attitudes and experience regarding oral surgery. PATIENTS AND METHODS: A
      telephone interview was used to address three areas of concern to both dental
      patients and dental professionals: surgery-related anxiety, anesthesia
      preferences, and preoperative information or counseling needs. Of the 1,008 adult
      respondents, 595 (57%) had undergone oral surgery at some time, 222 (22%) within
      the last 5 years. Among these patients, more than one in five (22%) had suffered
      anxiety levels high enough to delay them from seeking prompt treatment. An
      additional 31% reported moderate anxiety levels, whereas 48% reported no anxiety
      before oral surgery. RESULTS: Sixty-five percent of respondents preferred an
      anesthetic method that would allow them to be pain-free, but conscious, and 56%
      percent expressed a preference for anesthesia-induced amnesia. Virtually all
      respondents (98%) valued receiving pretreatment information about their oral
      surgery procedure and the type of anesthesia to be used. A substantial majority
      (90%) of respondents reported overall satisfaction with their oral surgery,
      rating their treatment as 3 or higher on a 6-point scale. CONCLUSION: The
      characteristics patients valued most in anesthesia-wakefulness, insensibility to
      pain, rapid recovery, and procedure-specific amnesia-all support a growing trend
      toward the routine use of conscious sedation in the oral and maxillofacial
      surgeon's office. Patients overwhelmingly want to know all about the procedure
      they will have, how it will be done, and what analgesic modalities are available.

PMID- 9191638
TI  - A comparison of skeletal stability after mandibular advancement and use of two
      rigid internal fixation techniques.
AB  - PURPOSE: Two different methods of rigid fixation were compared for postoperative
      stability 6 months after mandibular advancement for treatment of Class II
      malocclusion. MATERIAL AND METHODS: Sixty (30 + 30) patients from two different
      oral and maxillofacial units treated for a Class II malocclusion by bilateral
      saggital split osteotomy (BSSO), and two different methods of internal rigid
      fixation were prospectively investigated. Two groups (S1, n = 15; S2, n = 15) had
      bicortical noncompressive screws inserted in the gonial area through a
      transcutaneous approach, and the other two groups (P1, n = 15; P2, n = 15) had
      the bone segments fixed with unicortical screws and miniplates on the lateral
      surface of the mandibular body. Cephalograms were taken preoperatively, 2 days
      postoperatively and 6 months after the operation. A computer program was used to
      superimpose the three cephalograms and to register the mandibular advancement and
      postoperative change both sagittally and vertically. RESULTS: These were minor
      differences in the advancement and postoperative changes between the four groups,
      but statistically no significant difference was shown in either sagittal or
      vertical directions. However, statistically verified differences proved that
      increasing age was associated with a smaller amount of postsurgical relapse. Low
      angle cases (ML/NSL < 25 degrees) had a bigger amount of surgical (P = .0008) and
      postsurgical (P = .0195) movement compared with the patients in the high-angle
      group (ML/NSL < 38 degrees). Using a multiple regression test, a positive
      correlation was also shown between the amount of surgical advancement and the
      amount of postsurgical instability (P = .018). CONCLUSIONS: This prospective dual
      center study indicates that the two different methods of internal rigid fixation
      after surgical advancement of the mandible by BSSO did not significantly differ
      from each other, and it is up to the individual operator to choose the method for
      internal rigid fixation.

PMID- 9191639
TI  - Use of endosseous implants for dental reconstruction of patients with grafted
      alveolar clefts.
AB  - PURPOSE: The purpose of this study was to investigate the clinical application of
      endosseous implants placed into grafted alveolar clefts and to evaluate the short
      term outcome. PATIENTS AND METHODS: Nineteen patients (6 males and 13 females;
      mean age, 17.9 years; range, 9.7 to 33.6 years at first implant surgery),
      including 11 with unilateral cleft lip and palate, and eight with unilateral
      cleft lip and alveolus, were studied. All patients except for one who underwent
      periosteoplasty received grafts of autogenous particulate cancellous bone and
      marrow (PCBM) obtained from the llium. After bone bridge formation, orthodontic
      treatment and preparation for implant placement were performed. RESULTS: A total
      of 21 implants were placed in the bone-grafted alveoli of the 19 patients. The
      most frequently used length was 15 mm. In five patients with insufficient
      alveolar bone height, a chin bone onlay graft was combined with simultaneous
      implant insertion. The follow-up period ranged from 1 year to almost 3 years
      after implant placement, and the clinical outcome was excellent in all except one
      patient. In this short-term study, the overall survival rate was 90.5%.
      CONCLUSION: The grafted alveoli were well suited to the placement of endosseous
      implants, and this treatment was shown to be a viable option for the dental
      reconstruction of alveolar clefts. However, the interdental alveolar bone height
      was insufficient for implant installation in a few patients. Further longitudinal
      studies are required to determine the optimal timing between secondary bone
      grafting and implant placement.

PMID- 9191640
TI  - Trends in the incidence and cause of sport-related mandibular fractures: a
      retrospective analysis.
AB  - PURPOSE: This study assessed changes in the incidence and causes of mandibular
      fractures occurring in innsbruck, Austria between 1984 and 1993. PATIENTS AND
      METHODS: Records from 712 patients sustaining 982 mandibular fractures were
      reviewed and analyzed according to age, sex, date of fracture, place of trauma,
      cause, anatomic site of fracture, and associated orofacial and craniocerebral
      injuries. RESULTS: Sports were the most common cause of mandibular fractures,
      accounting for 31.5% of the entire sample, followed by road traffic accidents
      (27.2%) and falls (20.8%). The yearly distribution of sport-related mandibular
      fractures showed an increase from 28.6% in 1984 to 1988 to 34.5% in 1989 to 1993.
      The major causative factor in sports-related mandibular fractures was skiing
      (55.3%), whereas cycling and soccer accounted for 25.4% and 8.9%, respectively.
      Significant changes in the occurrence of cycling-related mandibular fractures
      were observed, with an increase of 19.3% from 1984 to 1988 to 1989 to 1993,
      whereas skiing-related mandibular fractures showed a decrease of similar
      magnitude (19.5%). Sex distribution showed a male-to-female ratio of 2.5:1, with
      the percentage of females involved increasing. In cases of cycling-related
      accidents, there was a considerable prevalence of associated injuries (133.3
      injuries per 100 mandibular fractures), with significantly higher rates of facial
      lacerations (73.2), tooth fractures (39), tooth luxations (24.4), and orbital
      fractures (3.7) than in the case of skiing-related injuries, whereas in patients
      sustaining mandibular fractures caused by soccer, mucosal lacerations, tooth
      luxations, and cerebral concussions were the only associated injuries found.
      CONCLUSIONS: The results of this study indicate a considerable change in the
      cause of mandibular fractures, showing that sporting injuries are becoming
      increasingly common. The high incidence of associated maxillofacial injuries in
      patients involved in skiing and cycling accidents may suggest an increasing need
      for preventive and protective measures.

PMID- 9191641
TI  - Utility of square-wave gratings to assess perioral spatial acuity.
AB  - PURPOSE: The usefulness of square-wave gratings to assess perioral spatial
      resolution acuity was evaluated. MATERIALS AND METHODS: A psychophysical tracking
      procedure was used to estimate the threshold groove width for discriminating
      orientation (horizontal or vertical) of square-wave gratings pressed into the
      skin. Ten positionally matched sites on the two sides of the face of 36 right
      handed, healthy young adults were studied. Commercially available gratings
      provided alternating ridge- and-groove stimuli with element widths from 0.35 to
      3.0 mm. RESULTS: Thirty-three of the 36 subjects could discriminate orientation
      at all six sites on the vermilion (threshold width averaged 1.06 mm for grooves
      and for ridges). Thresholds were lower on the mid-portion of the lower vermilion
      than on the mid-portion of the upper vermilion (P < .05). Moreover, thresholds
      were lower on the right side of the vermilion than on the left side (P < .02). In
      contrast to the vermilion, only 25 and 30 subjects could discriminate orientation
      on the left and right hairy upper lip, respectively; and two or fewer subjects,
      at each of 12 sites on the chin and cheeks. CONCLUSIONS: Clinical use of small
      square-wave gratings with ridge and groove widths of 3 mm or smaller is limited
      to the vermilion. Moreover, baseline values are needed for individual patients to
      minimize false-positive diagnoses of sensory impairment. The size required of
      coarser gratings to test other perioral sites may preclude their use for
      evaluation of discrete, suspect skin areas.

PMID- 9191642
TI  - Wurzburg lag screw plate versus four-hole miniplate for the treatment of condylar
      process fractures.
AB  - PURPOSE: The purpose of this study was to compare the biomechanical stability of
      rigidly fixed condylar neck fractures using either a conventional four-hole
      miniplate system or the Wurzburg lag screw plate system. MATERIALS AND METHODS:
      Ten identical synthetic mandibles were used for this study. Simulated bilateral
      condylar neck fractures were fixed with the lag screw plate system on one side
      and the miniplate system on the other. The mandibles were loaded with an MTS
      servohydraulic testing machine at a rate of 1 cm/min until failure was reached.
      Data for resistance to motion and ultimate strength for each fixation device were
      compared by paired Student t-tests. RESULTS: The mean resistance to motion for
      the four-hole miniplate was 64.0 kg/mm (SD = 10.1; range = 52-94) and for the lag
      screw system was 80.2 kg/mm (SD = 24.0; range = 55 to 126). The mean failure
      strength was 4.0 kg (SD = 0.9) (range = 2.6 to 5.5) for the miniplate system and
      5.0 kg (SD = 2.5; range = 3.4 to 7.2) for the lag screw system. The lag screw
      system was significantly (P < .05) better than the miniplate for both parameters
      measured. CONCLUSION: In laboratory testing using synthetic mandibles, the
      Wurzburg lag screw-plate fixation system proved superior to a four-hole miniplate
      system in regard to resistance to motion and failure strength. Clinical trials
      are necessary to substantiate these laboratory data and determine whether the
      system can be effectively applied by the surgeon.

PMID- 9191643
TI  - Recurrent chin swelling.

PMID- 9191644
TI  - The molecular biology of oral carcinogenesis: toward a tumor progression model.
AB  - PURPOSE: An understanding of the molecular basis of oral carcinogenesis will
      alter our clinical approach to oral cancer. The nomenclature and major themes of
      molecular oral tumor biology are reviewed, beginning with the regulation events
      governing normal cellular physiology. In carcinogenesis, chromosomal or
      cytogenetic alterations lead to deregulation of tightly controlled stimulatory
      and inhibitory pathways, growth-promoting proto-oncogenes are mutated into
      overactive oncogenes, and growth-suppressing or tumor suppressor genes are
      inactivated. Recent advances in defining these fundamental mechanisms of tumor
      biology may allow prevention, diagnosis, and treatment of oral cancer to be
      approached at the molecular level.

PMID- 9191645
TI  - Gastrointestinal cyst of the tongue: a possible duplication cyst of foregut
      origin.

PMID- 9191646
TI  - Basaloid monomorphic adenoma presenting as an expanding buccal mass: a case
      report.

PMID- 9191647
TI  - Application of B-scan ultrasonography for analysis of callus distraction in
      vascularized fibular grafts of the mandible: a report of three patients.

PMID- 9191648
TI  - Esophageal carcinoma metastatic centrally to the mandible: a case report with
      implication of cell proliferating marker Ki-67.

PMID- 9191649
TI  - Bilateral dislocation of the temporomandibular joints in a 2-year-old child:
      report of a case.

PMID- 9191650
TI  - Reversal of blindness after facial fracture repair by prompt optic nerve
      decompression.

PMID- 9191651
TI  - Hyoid myotomy and suspension for obstructive sleep apnea syndrome.

PMID- 9191652
TI  - A Canadian National Trauma Registry: the time is now.

PMID- 9191653
TI  - Lateral impact motor vehicle collisions: significant cause of blunt traumatic
      rupture of the thoracic aorta.
AB  - BACKGROUND: This study was undertaken to determine the relationship between
      traumatic rupture of the thoracic aorta (TRA) and the direction of impact at the
      time of motor vehicle crash. METHODS: Retrospective review of TRA patients from
      two different databases over a 4.5-year period (January 1, 1991 to June 30,
      1995): (1) Ontario Coroner's Office records of motor vehicle deaths from
      Metropolitan Toronto, and (2) the trauma registries of Sunnybrook Health Science
      Centre and St. Michael's Hospital in Metropolitan Toronto. RESULTS: Ninety-seven
      patients (81 from the coroner's database and 16 from the adult trauma unit
      registries) sustained traumatic rupture of the thoracic aorta. Forty-eight cases
      (49.5%) were a result of lateral impact crashes. Twenty-eight drivers (22
      ipsilateral and six contralateral) and 20 passengers (16 ipsilateral and four
      contralateral) sustained TRA from lateral impact crashes. Ninety-one TRAs (94%)
      occurred at the peri-isthmic region. CONCLUSION: Lateral impact crashes are a
      significant cause of TRA. Traumatic rupture of the aorta should be considered
      with a high index of suspicion after serious lateral impact crashes, just as
      physicians now consider patients at high risk of TRA after serious frontal impact
      crashes.

PMID- 9191654
TI  - Long-term outcomes in open pelvic fractures.
AB  - BACKGROUND: Open pelvic fractures represent one of the most devastating injuries
      in orthopedic trauma. The purpose of this study was to document the injury
      characteristics, complications, mortality, and long-term, health-related quality
      of life outcomes in patients with open pelvic fractures. METHODS: The trauma
      registry at an adult trauma center was used to identify all multiple system blunt
      trauma patients with a pelvic fracture from January of 1987 to August of 1995 (n
      = 1,179). Demographic data, mechanism of injury, and fracture type were
      determined from hospital records. Short-term outcome measures included infectious
      complications, mortality, and length of stay in hospital. Long-term outcomes of
      survivors were obtained by telephone interview using the SF-36 Health Survey and
      the Functional Independence Measure. RESULTS: Open pelvic fractures were
      uncommon, occurring in 44 patients (4%). Patients with open fractures were about
      9 years younger, on average, than patients with closed fractures (30 vs. 39, p <
      0.001). Similarly, patients with open fractures were more likely to be male (75
      vs. 57%, p < 0.02), more likely to have been involved in a motorcycle crash (27
      vs. 6%, p < 0.001), and more likely to have an unstable pelvic ring disruption
      (45 vs. 25%, p < 0.001). Open pelvic fracture patients required more blood than
      closed pelvic fracture patients, both in the first day (16 vs. 4 units, p <
      0.001) and during the total hospital admission (29 vs. 9 units, p < 0.001). Five
      patients with perineal wounds did not receive a diverting colostomy; in turn,
      these individuals had a total of six pelvic infectious complications (one
      abscess, two with osteomyelitis, and three perineal wound infections). Overall,
      11 patients died, six patients were lost to follow-up, and 27 were long-term
      survivors (mean duration of 4 years). Chronic disability was common after a
      pelvic fracture, with problems related to physical role performance and physical
      functioning, and was particularly severe after an open pelvic fracture (p < 0.05
      for both as measured by the SF-36). CONCLUSIONS: Patients with open pelvic
      fractures often survive, need to be treated with massive blood transfusions, and
      often require a colostomy. They are frequently left with chronic pain and
      residual disabilities in physical functioning and physical roles, and many remain
      unemployed years after injury.

PMID- 9191655
TI  - Long-term outcomes in blunt trauma: who goes back to work?
AB  - BACKGROUND: Trauma patients continue to improve after discharge from the trauma
      center, but the completeness of this recovery remains uncertain. The purpose of
      this study was to compare the characteristics of patients who do and who do not
      return to work after blunt trauma. METHODS: Consecutive survivors of blunt trauma
      discharged from a regional trauma center over a 1-year interval (July of 1994 to
      June of 1995) were included in the study. Patients completed the SF-36 Health
      Survey and some additional questions related to employment status both at
      discharge and again after 1 year. Our principal analysis compared patients who
      were employed and unemployed at 1-year follow-up. RESULTS: Complete data were
      available for 195 patients. The typical patient was a young man who had been in a
      motor vehicle collision and had an injury severity score of 25. At 1-year follow
      up, 101 patients had returned to work and 94 remained unemployed. Employed
      individuals were younger (31 vs. 44 years, p < 0.0001), less severely injured
      (mean injury severity score 23 vs. 27, p < 0.001), and more likely to hold
      professional jobs (50 vs. 16%, p < 0.0001). Patterns of injury and operative
      procedures were similar for employed and unemployed patients. However, the
      average employed patient had fewer days in the intensive care unit (2 vs. 5 days,
      p < 0.001), a shorter total hospitalization (19 vs. 28 days, p < 0.01), and was
      more likely to be discharged to home (62 vs. 39%, p < 0.01). At discharge, those
      who went on to employment had marginally better SF-36 Health Survey scores on
      seven of the eight scales (all except general health). During the year after
      discharge, both groups improved significantly, although employed individuals to a
      greater extent on all scales of the SF-36 Health Survey. CONCLUSIONS: Almost one
      half of the multiple system blunt trauma patients remain unemployed 1 year after
      hospital discharge. Those patients who return to work are usually young
      professionals with a lower severity of injury. Functional status at discharge
      predicts future employment status, but underestimates the extent of long-term
      recovery.

PMID- 9191656
TI  - Predictors of fetal mortality in pregnant trauma patients.
AB  - BACKGROUND: Fetal mortality after trauma is significant. This study was aimed at
      identifying factors responsible for this high fetal mortality. METHODS: All
      pregnant trauma patients admitted to the two major Toronto trauma institutions
      during the period of November of 1991 to February of 1996 with an Injury Severity
      Score (ISS) > or = 12 were assessed. Data on age, gestation, hypotension, ISS,
      hemoglobin, blood transfusion, length of stay, disseminated intravascular
      coagulation (DIC), and specific maternal injury were analyzed retrospectively to
      determine predictors of fetal mortality by comparison of patients with and
      without fetal survival. RESULTS: Twenty of a total of 68 pregnant trauma patients
      qualified for entry into the trauma registry by having an ISS > or = 12. Overall
      fetal mortality was 65% (13 of 20) for ISS > or = 12, and there was one maternal
      death (age, 29 years; ISS, 66). There were no statistically significant
      differences between the fetal death and fetal survival groups in age (29.2 +/-
      6.2 vs. 30.4 +/- 3.9 years), gestation (25.3 +/- 10.5 vs. 24.1 +/- 9.2 weeks),
      lowest systolic blood pressure (98.3 +/- 33.8 vs. 112 +/- 18.0 mm Hg), head
      injury rate (3 of 13 vs. 1 of 7), extremity injury rate (8 of 13 vs. 2 of 7),
      abdominal injury rate (4 of 13 vs. 0 of 7), pelvic fracture rate (6 of 13 vs. 1
      of 7), and chest injury rate (5 of 13 vs. 3 of 7). However, ISS (27.7 +/- 3.5 vs.
      14.2 +/- 11.4), lowest hemoglobin level (78.8 +/- 17.0 vs. 101.9 +/- 17.1), blood
      transfusions (10.8 +/- 6.3 vs. 0.9 +/- 1.6 units), length of stay (20.9 +/- 16.7
      vs. 8.2 +/- 4.9 days), and the incidence of DIC (8 of 13 vs. 0 of 7) were
      statistically significantly different between the two groups (p < 0.05). All
      eight patients with abruptio placentae had associated fetal mortality.
      CONCLUSIONS: Apart from ISS, blood loss, and abruptio placentae; the presence of
      DIC was the most significant predictor of fetal mortality. This finding may
      represent stimulation of DIC by placental products entering the maternal
      circulation after significant intrauterine injury.

PMID- 9191657
TI  - Effect of the prehospital trauma life support program (PHTLS) on prehospital
      trauma care.
AB  - BACKGROUND: Improvement in trauma patient outcome has been demonstrated after the
      implementation of the Prehospital Trauma Life Support (PHTLS) program in Trinidad
      and Tobago. This study was aimed at identifying prehospital care factors that may
      explain this improvement. METHODS: All patients transferred by ambulance to the
      major trauma referral hospital had assessment of airway control, oxygen use,
      cervical (C)-spine control, and hemorrhage control, as well as splinting of
      extremities during pre-PHTLS (July of 1990 to December of 1991; n = 332) and post
      PHTLS periods (January of 1994 to June of 1995; n = 350). Pre-PHTLS data were
      compared with post-PHTLS data by chi 2 analysis with a p value < or = 0.05 being
      considered statistically significant. RESULTS: The frequency (%) increased in the
      post-PHTLS period for airway control (10 vs. 99.7%), C-spine control (2.1 vs.
      89.4%), splinting of extremities (22 vs. 60.6%), hemorrhage control (16 vs.
      96.9%), and oxygen use (6.6 vs. 89.5%) when no specific problem was identified.
      When a specific problem was identified in these areas, the post-PHTLS percentage
      also increased for airway control (16.2 vs. 100%), C-spine control (25 vs. 100%),
      splinting of extremities (33.9 vs. 100%), hemorrhage control (18 vs. 100%), and
      oxygen use (43.2 vs. 98.9%). CONCLUSIONS: Prehospital trauma care has changed
      after the introduction of the PHTLS program as indicated by more frequent airway
      control, use of oxygen, control of cervical (C)-spine and hemorrhage, as well as
      splinting of fractures. This finding was evident not only as a routine but
      particularly when a specific related problem was identified. This change in
      prehospital care could be responsible for the improved trauma patient outcome
      after PHTLS.

PMID- 9191658
TI  - Recovery of biceps function after delayed repair for brachial plexus injury.
AB  - BACKGROUND: In many cases of severe closed injury involving the upper trunk of
      the brachial plexus, the proximal stump is too damaged to permit direct repair.
      Under these circumstances, several alternative sources of neurotization have been
      described, three of which are analyzed here. METHODS AND RESULTS: Thirteen
      patients with brachial plexus injury had paralysis of elbow flexion owing to
      damage of either the upper trunk or the lateral cord. In four patients, the
      musculocutaneous nerve was reinnervated through cross-union with the
      thoracodorsal nerve; all regained strong elbow flexion. One of three the patients
      with cross-union between the lateral or medial pectoral nerve regained useful
      elbow flexion. Of six patients with nerve grafting between spinal accessory and
      musculocutaneous nerves, four regained useful elbow flexion. CONCLUSION: Cross
      union between thoracodorsal and musculocutaneous nerves appears to be a reliable
      method of restoring elbow function even when delayed for 2 years after injury.
      Return of elbow flexion should be an obtainable goal in most brachial plexus
      injuries.

PMID- 9191660
TI  - Effect of thyroid hormone (T3)-responsive changes in surfactant apoproteins on
      surfactant function during sepsis.
AB  - BACKGROUND: Long surfactant phospholipids are altered during sepsis; the role of
      surfactant apoproteins is unknown. This study investigates the effect of cecal
      ligation and puncture (CLP) on surfactant functional effectiveness and apoprotein
      transcriptional activity with or without T3 replacement. METHODS: Male Sprague
      Dawley rats underwent sham laparotomy or CLP with or without T3 replacement. Lung
      compliance, surfactant adsorption, and surface tension were measured with a
      surfactometer. Surfactant apoproteins A, B, and C (SP-A, SP-B, SP-C) mRNA was
      quantified by Northern blot analysis. RESULTS: Lung compliance was significantly
      decreased by sepsis; initial surface tension and adsorption values in CLP animals
      reflected apoprotein dysfunction. Sepsis decreased SP-A mRNA levels and increased
      SP-B mRNA; SP-C mRNA were unchanged. T3 treatment improved compliance,
      adsorption, and ST isotherms in septic animals. CONCLUSION: T3 attenuated sepsis
      induced surfactant dysfunction and SP-A and SP-B transcriptional changes during
      sepsis. This suggests an interaction between the thyroid, surfactant apoproteins,
      and lung surfactant functional effectiveness and requires further study.

PMID- 9191659
TI  - Randomized trial of immune-enhancing enteral nutrition in burn patients.
AB  - BACKGROUND: "Immune-enhancing" diets (IEDs) are aimed at improving outcomes in
      patients suffering trauma and infection. This study was conducted to evaluate a
      popular IED in patients suffering burn injury. METHODS: Fifty burned patients
      were randomized to receive either Impact (Sandoz Nutrition, Minneapolis, Minn),
      an IED enhanced with omega-3 fatty acids, arginine, and RNA, or Replete (Clintec,
      Deerfield, Ill), our standard high-protein diet. Feedings were begun within 48
      hours of injury, and continued until patients supported themselves with oral
      intake. RESULTS: Forty-nine patients completed the study. The two feeding groups
      did not differ with respect to age, burn size, incidence of inhalation injury, or
      the quantity of calories and protein received. There were no differences between
      groups in mortality, length of hospitalization, hospital charges, days of
      ventilator support, or incidence of complications. Patients with inhalation
      injuries required more ventilatory support, and had longer lengths of
      hospitalization and higher costs. CONCLUSIONS: Administration of an IED has no
      clear advantages over the use of less expensive high-protein enteral nutrition in
      burn patients.

PMID- 9191661
TI  - Benchmarking the quality-monitoring process: a comparison of outcomes analysis by
      trauma and injury severity score (TRISS) methodology with the peer-review
      process.
AB  - BACKGROUND: One measure of optimal function within a trauma center is the ability
      to critically examine outcomes from the process of care within the institution,
      yet guidelines for evaluation of the peer-review process are lacking. This study
      was conducted to determine the correlation between mortality analysis performed
      by the peer-review process (PR) within a trauma division and outcome analysis as
      determined by Trauma and Injury Severity Score (TRISS) methodology. METHODS: The
      mortality peer-review data for an entire year at our level I trauma center served
      as the study population. Information was obtained on probability of survival, and
      a determination of preventability was made using standard, preexisting criteria.
      Peer review involves assigning each outcome to a specific category through the
      process of multidisciplinary assessment. Probability of survival data was not
      used for this purpose. Kappa analysis was performed to determine the degree of
      agreement in each category and then tested for significance. RESULTS: One hundred
      four deaths in 1,868 trauma patients (5.5%) were reviewed at our
      multidisciplinary conference. Outcomes were judged as preventable, potentially
      preventable, or nonpreventable. Death directly related to exsanguination was
      typically categorized as potentially preventable. Kappa analysis demonstrated the
      greatest agreement between PR and TRISS in the nonpreventable category (kappa =
      0.213) and the least agreement in the potentially preventable category (kappa = 
      0.197). Overall, the kappa Z statistic was nonsignificant (Z = 1.24).
      CONCLUSIONS: Multidisciplinary peer-review outcomes analysis is at least as
      effective as the computer-generated TRISS probability of survival data for
      evaluating quality of care in a trauma center and may be more effective for
      analysis of potentially preventable outcomes.

PMID- 9191662
TI  - Neurosurgical trauma call: use of a mathematical simulation program to define
      manpower needs.
AB  - Resource criteria for trauma centers (TC) mandate a first plus backup
      neurosurgeon (NS) coverage, an unnecessary expense for TC treating few
      neurosurgery patients. This report uses a mathematical modeling system to define
      optimal NS trauma coverage. Random data from 749 patients treated with emergency
      neurosurgery operations (OR) within 24 hours of admission at 97 TC were used to
      create a 1-year profile of admission by month, day, and hour, operation times,
      and operation duration. These data were entered into a simulation program to
      define the frequency that a patient needing a NS consult would wait beyond 30
      minutes because the NS was in the operating room at a trauma center with one,
      two, or three neurosurgeons on-call. One thousand iterations were done for each
      sample size of 25 to 300 patients in 25-patient increments. The probability that
      a patient could not be seen promptly by one NS in a trauma center operating on
      25, 50, 75, or 100 patients per year is 0.23, 0.9, 1.6, and 3.66 patients per
      year. Fewer than one patient (0.75) per year will wait more than 30 min in a
      trauma center doing 225 emergency ORs when two neurosurgeons are on-call. One
      patient in 10 years would wait more than 30 min in a trauma center doing 300 ORs
      with a third NS on-call. Mathematical modeling of patient data helps define
      optimal hospital resources. Mandatory NS backup for TC performing fewer than 25
      neurosurgery procedures is unneeded.

PMID- 9191663
TI  - Diagnostic and therapeutic laparoscopy for penetrating abdominal trauma: a
      multicenter experience.
AB  - BACKGROUND: Considerable skepticism still exists about the role of diagnostic
      laparoscopy in the evaluation of penetrating abdominal trauma. The reported
      experience with therapeutic laparoscopy has been limited. METHODS: Retrospective
      analysis of a collective experience from three large urban trauma centers with
      510 patients (316 stab wounds, 194 gunshot wounds) who were hemodynamically
      stable and had no urgent indications for celiotomy. RESULTS: Laparotomy was
      avoided in 277 of the 510 patients (54.3%) either because of nonpenetration or
      insignificant findings on laparoscopy. All were discharged uneventfully after a
      mean hospital stay of 1.7 days. Twenty-six had successful therapeutic procedures
      on laparoscopy (diaphragmatic repair in 16 patients, cholecystectomy in 1
      patient, hepatic repair in 6 patients, and closure of gastrotomy in 3 patients)
      with uneventful recovery. In the remaining 203 patients, laparotomy was
      therapeutic in 155. Fifty-two patients had nontherapeutic celiotomy for exclusion
      of bowel injuries or as mandatory laparotomy for penetrating gunshot wounds
      (19.7%). The overall incidence of nontherapeutic laparotomy was 10.2%.
      Complications from laparoscopy were minimal (10 of 510) and minor. CONCLUSIONS:
      Laparoscopy has an important diagnostic role in stable patients with penetrating
      abdominal trauma. In carefully selected patients, therapeutic laparoscopy is
      practical, feasible, and offers all the advantages of minimally invasive surgery.

PMID- 9191664
TI  - Efficacy of prehospital surgical cricothyrotomy in trauma patients.
AB  - OBJECTIVE: The use of surgical cricothyrotomy (SC) in the prehospital setting is
      controversial, and the need to teach this procedure to paramedics and
      intermediate emergency medical technicians remains unclear. The purpose of this
      study is to define the efficacy, complication rate, and overall survival after SC
      performed in the prehospital setting. METHODS: In our region, emergency medical
      technicians receive training in this technique using an animal model with bi
      annual updates required. We retrospectively reviewed data in our regional trauma
      register (15,686 injured patients) for the years 1991-1995. RESULTS: Prehospital
      emergency airway intubation was required in 376 patients, 56 of whom received SC.
      The primary indications for SC were facial fractures and deformities (32%) and
      blood in the airway (30%). In 79% of the patients requiring SC, attempted
      orotracheal intubation prior to SC was unsuccessful, with a mean of 1.9 attempts
      per patient. SC was judged to provide an adequate airway in the field in 89% of
      attempts. Complications at the scene included six failed attempts, one case of
      excessive bleeding, and one adverse patient reaction (agitation). When patients
      arrived at the trauma center, the SC was judged to be acceptable in 64%, whereas
      16% were functioning with some question of adequacy and required airway
      manipulation (most commonly a mainstem bronchial intubation). Overall survival to
      hospital discharge was 27%; however, survival to emergency department discharge
      (an indicator of emergency airway adequacy) was 62%. Using TRISS methodology,
      there were five unexpected survivors and six unexpected deaths. Only three
      patients were discharged with a "good neurologic recovery." CONCLUSION: (1)
      Prehospital SC can be performed effectively with few complications after training
      on animal models (2) Good neurologic outcome is rare after the use of this
      procedure. (3) Although it is effective, clear indications must be developed and
      followed for the prehospital use of SC.

PMID- 9191665
TI  - Right ventricular volumes overestimate left ventricular preload in critically ill
      patients.
AB  - BACKGROUND: Studies have shown right ventricular end-diastolic volume (RVEDV) to
      be a more accurate estimate of left ventricular preload than pulmonary artery
      wedge pressure. We prospectively evaluated the ability of RVEDV to predict left
      ventricular end-diastolic volume (LVEDV) in critically ill patients. METHODS:
      Thirty critically ill patients in the surgical intensive care unit underwent
      concurrent measurement of RVEDV and LVEDV. RVEDV was measured using a residual
      fraction Swan-Ganz catheter (RF Swan). LVEDV was measured using transesophageal
      echocardiography with acoustic quantification. Intracardiac, intra-abdominal, and
      ventilatory pressures were also measured. RESULTS: RVEDV as measured by the RF
      Swan was significantly larger (by a factor of 2) than LVEDV (p < 0.0001 analysis
      of variance). However, the RVEDV and LVEDV were strongly correlated (r = 0.71, p
      < 0.0001, Pearson's correlation). CONCLUSIONS: RVEDV from the RF Swan markedly
      overestimated left ventricular preload. If RVEDV is used as an absolute value for
      determining preload, patients may be underresuscitated. Transesophageal
      echocardiography in conjunction with RF Swan can be used to more accurately
      determine preload and cardiac performance than RF Swan alone in critically ill
      patients.

PMID- 9191666
TI  - Pulmonary hypertension and systemic vasoconstriction may offset the benefits of
      acellular hemoglobin blood substitutes.
AB  - OBJECTIVE: We tested the hypothesis that the pharmacologic properties of a small
      volume of alpha alpha-cross-linked hemoglobin (alpha alpha Hb) could effectively
      resuscitate pigs subjected to hemorrhage. METHODS: Fourteen pigs hemorrhaged to a
      mean arterial pressure (MAP) of 40 mm Hg for 60 minutes were treated with a 4
      mL/kg 2-minute infusion of 10 g/dL alpha alpha Hb or 7 g/dL human serum albumin,
      an oncotically matched control solution. RESULTS: The removal of blood (17 +/-
      1.5 mL/kg) caused the typical physiologic responses to hemorrhagic hypovolemia.
      Infusion of alpha alpha Hb restored mean arterial pressure and coronary perfusion
      pressure, but cardiac output and mixed venous O2 saturation did not improve
      significantly. Pulmonary arterial pressure and pulmonary vascular resistance
      increased markedly and were higher than baseline levels after alpha alpha Hb.
      Infusion of human serum albumin produced only minor hemodynamic changes. Brain
      blood flow did improve to baseline values after alpha alpha Hb, but was the only
      tissue to do so. In the human serum albumin group, superior mesenteric artery
      blood flow recovered to baseline values, whereas brain blood flow did not. Blood
      flows to other tissues were similar in both groups. CONCLUSION: Small-volume
      infusion of alpha alpha Hb restored mean arterial pressure and brain blood flow,
      but pulmonary hypertension and low peripheral perfusion may offset benefits for
      trauma patients.

PMID- 9191668
TI  - Relationship of interleukin-10 plasma levels to severity of injury and clinical
      outcome in injured patients.
AB  - Interleukin-10 (IL-10) markedly inhibits lymphocyte and phagocytic functions,
      which are essential for an adequate immune response to invading microbes.
      Although various animal and clinical studies revealed an increased release of IL
      10 during sepsis, alterations of circulating IL-10 after injury and potential
      relationships to severity of injury and clinical outcome are unknown. Injured
      patients (n = 417) showed elevated (p < 0.001) IL-10 levels throughout the
      observation period of 21 days compared with healthy volunteers (n = 137).
      Patients with severe injury (Injury Severity Score > or = 25 points) demonstrated
      significantly increased IL-10 levels compared with patients with minor trauma
      (Injury Severity Score < 25 points). Patients who died from injury or developed
      posttraumatic complications (sepsis, multiple organ dysfunction syndrome)
      revealed elevated IL-10 levels in comparison with injured patients with
      uneventful posttraumatic course. Thus, trauma causes an enhanced release of IL-10
      dependent on the severity of injury. Because increased IL-10 levels are
      significantly related to posttraumatic complications, IL-10 may be involved in
      their pathogenesis.

PMID- 9191667
TI  - Predicting life-threatening coagulopathy in the massively transfused trauma
      patient: hypothermia and acidoses revisited.
AB  - BACKGROUND: Recalcitrant coagulopathy "the bloody vicious cycle," produces the
      majority of deaths after torso trauma. A model predicting this life-threatening
      complication may facilitate clinical decision-making. METHODS: We prospectively
      analyzed patients > 15 years old who received a massive transfusion (> 10 units
      of packed red blood cells (PRBC)/24 h) over a 2-year period. Excluding massive
      head injuries and pre-existing disease, the 58 study patients had a mean age =
      35.4 years, Injury Severity Score (ISS) = 30.6, and PRBC = 24.2 units/24 h.
      RESULTS: Defined as prothrombin time of two times that of normal laboratory
      controls and partial thromboplastin time as two times that of normal laboratory
      controls, 27 patients (47%) developed life-threatening coagulopathy. Using a
      multiple logistic regression model, the four significant risk factors (with odds
      ratio) were (1) pH < 7.10 (12.3), (2) temperature < 34 degrees C (8.7), (3) ISS >
      25 (7.7), and (4) systolic blood pressure < 70 mm Hg (5.8). The conditional
      probability of developing coagulopathy was ISS > 25 + systolic blood pressure <
      70 mm Hg = 39%, ISS > 25 + temperature < 34 degrees C = 49%, ISS > 25 + pH < 7.10
      = 49%; with all four risk factors the incidence was 98%. CONCLUSION: Postinjury
      life-threatening coagulopathy in the seriously injured requiring massive
      transfusion is predicted by persistent hypothermia and progressive metabolic
      acidosis.

PMID- 9191669
TI  - Postburn constitutional changes in T-cell reactivity occur in CD8+ rather than in
      CD4+ cells.
AB  - BACKGROUND: Impairment of T-helper cell function and polarization toward T-helper
      2-type cytokine synthesis have been postulated to represent a major cause for
      posttraumatic immunodeficiency. With a recently developed technology for
      intracellular cytokine measurement, a new diagnostic tool has become available to
      discriminate, within hours, a shift of functionality in T-cell subsets via their
      individual cytokine profiles. Thus, it was the objective of this study to obtain
      further insight into the constitutional, phenotype-dependent changes of T-helper
      1 (TH1) and T-helper 2 (TH2), respectively, signature lymphokine synthesis under
      traumatic stress. METHODS: Peripheral blood mononuclear cells from 10 patients
      with major burn injury on day 1, 3, 5, and 7 after injury and from 15 healthy
      individuals were separated and incubated (5 hours) for cytokine production
      induced with the accessory cell-independent stimulus of ionomycin and phorbol 12
      myristate 13-acetate. After fixation and permeabilization, cell samples were
      immunofluorescently stained for cell surface antigens (CD4 and CD8) as well as
      for intracellular interferon (IFN)-gamma and interleukin (IL)-4 synthesis.
      Results were correlated with corresponding enzyme-linked immunosorbent assay
      measurements of the culture supernatants. RESULTS: Phenotypic assessment of
      peripheral blood mononuclear cells showed a continuously diminished percentage of
      CD8+ cells during the immediate posttraumatic course compared with controls,
      whereas the number of CD4+ cells was found to be within the range of the control
      group. The production of IL-4, the index cytokine of TH2 cells, was excessively
      up-regulated (from 437.8 +/- 137.0 pg/mL on day 1 to 1,333.6 +/- 532.7 pg/mL on
      day 7 burns vs. 82.3 +/- 15.8 pg/mL controls), whereas the release of IFN-gamma,
      the index cytokine of TH1 cells, however, was only slightly increased. The
      predominant cellular source of IL-4 after burn trauma has been shown to be the
      CD8+ cell with a nearly fivefold elevated production on day 5 (7.2 +/- 2.6%)
      versus 1.5 +/- 0.4% in controls. Although CD8+ cells are also capable of
      enhancing their IFN-gamma synthesis under stress by about 60%, the CD4+ IFN-gamma
      release remained largely unchanged. CONCLUSION: Our data corroborate that major
      burn trauma will induce a significant shift of cytokine response toward the TH2
      direction and demonstrate that the CD8+ rather than the CD4+ phenotype is the
      crucial cell for the polarization toward a TH2-driven immune response.

PMID- 9191670
TI  - Mechanism of splenic immunosuppression during sepsis: key role of Kupffer cell
      mediators.
AB  - Studies indicate that the liver, in particular the Kupffer cells, appear to be
      key contributors in the systemic inflammatory mediator response associated with
      shock and sepsis. Although several of these agents have been implicated as
      mediators of depressed immunoresponsiveness observed during sepsis, it remains
      unknown whether or not mediators released specifically by Kupffer cells play any
      significant role in producing the cellular dysfunction in distant organs. The aim
      of this study, therefore, was to determine whether or not acute Kupffer cell
      reduction before the onset of sepsis would protect splenic lymphocyte function.
      Kupffer cell number was reduced by prior (48 hours) treatment of mice with
      gadolinium chloride (GdCl2, 10 mg/kg of body weight, intravenously) or saline
      vehicle. Animals were then subjected to either sham-CLP (sham) or polymicrobial
      sepsis in the form of cecal ligation and puncture (CLP). Plasma and splenocytes
      were harvested at 2 or 24 hours after CLP. Splenocyte cultures were exposed to
      2.5 micrograms concanavalin A/mL to assess their ability to release lymphokines.
      Cytokine (interleukin (IL)-2, IL-6, interferon-gamma, tumor necrosis factor
      alpha) concentration in plasma or cell supernatants was assessed by bioassay. The
      results indicated that GdCl2 treated mice exhibited a marked reduction in
      circulating IL-6 levels at both 2 and 24 hours after CLP. Furthermore, the
      reduction of Kupffer cell number before the onset of sepsis completely prevented
      the depression of splenocyte IL-2 and interferon-gamma release, capacity. Thus
      mediators released by Kupffer cells during the systemic inflammatory response to
      polymicrobial sepsis play a significant role in producing immune dysfunction in
      resident splenic lymphocytes. In view of this, it appears that modulation of
      Kupffer cell hyperactivity during sepsis may be a novel approach for maintaining
      distant organ host defense mechanisms.

PMID- 9191671
TI  - Altered monocyte calcium dynamics in sepsis.
AB  - PURPOSE: This study was designed to evaluate monocyte calcium concentration and
      mobilization in normal and septic surgical patients. METHODS: Monocytes were
      isolated from 15 "septic" surgical patients, washed, and loaded with the
      fluorescent calcium chelator, FURA-2. Monocytes from 20 normal volunteers served
      as controls. Intracellular calcium concentration ([Ca2+]i) was measured by means
      of fluorescent spectrophotometry before, during, and after stimulation with
      concanavalin A. Differences were evaluated for statistical significance by
      analysis of variance. The study was repeated using normal monocytes preincubated
      in "septic" serum and "septic" monocytes preincubated in normal serum. Additional
      paired whole blood specimens were obtained from the control group and were
      incubated with Escherichia coli endotoxin. Monocytes were then isolated and
      evaluated as described. RESULTS: Sepsis was associated with significantly low
      resting monocyte calcium concentrations. Although concanavalin A stimulation
      resulted in marked calcium mobilization in both normal and septic cells, final
      cellular calcium concentration was significantly lower in the stimulated "septic"
      monocytes. Similar alterations were seen in normal cells incubated with septic
      serum, but could not be reproduced by incubation with endotoxin. This deficiency
      could not be corrected in septic cells incubated in normal serum. CONCLUSION:
      Sepsis is associated with a significant alteration of monocyte calcium dynamics
      in both resting and stimulated cells. These changes appear to be modulated by a
      serum factor other than endotoxin.

PMID- 9191672
TI  - The immune microenvironment of human fracture/soft-tissue hematomas and its
      relationship to systemic immunity.
AB  - The immune environment of human soft-tissue injury is unstudied. We studied
      fracture soft-tissue hematomas (FxSTH) in 56 patients with high-energy bony
      fractures. FxSTH serum and mononuclear cells (MNC) as well as fracture patient
      plasma and blood MNC were studied. Twenty healthy controls donated plasma and
      MNC. Soluble tumor necrosis factor (TNF)-alpha, interleukin (IL-1 beta, IL-2, 6,
      8, 10, 12, and interferon-gamma were studied by enzyme linked immunosorbent
      assay. Cells were studied by flow cytometry after cell-membrane stains for CD-14,
      TNF-alpha (mTNF), and human leukocyte antigen-DR, or intracellular stains for TNF
      (icTNF) and IL-10. Thirty-six patients with Injury Severity Score < 15 were
      analyzed further to evaluate the effects of isolated fracture on systemic
      immunity. Cytokines were rarely detectable in control plasma. TNF-alpha, IL-1
      beta, IL-2, and interferon-gamma were rarely found in FxSTH serum or fracture
      patient plasma. All FxSTH sera were rich in IL-6, peaking before 48 hours (12,538
      +/- 4,153 vs. 3,494 +/- 909 pg/mL, p = 0.02, U test). In Injury Severity Score <
      15, IL-6 was not detectable in most early fracture patient plasma, but rose after
      48 hours (p = 0.028). FxSTH serum IL-8 peaked after 48 hours (440 +/- 289 vs.
      4,542 +/- 1,219 pg/mL, p = 0.006) and circulating IL-8 appeared after 72 hours.
      IL-6 and IL-8 showed gradients from FxSTH serum to paired PtS (p < 0.05,
      Wilcoxon). IL-10 was abundant (884 +/- 229 pg/mL) in FxSTH serum < 24 hours old.
      FxSTH serum IL-12 peaked late (3,323 +/- 799 pg/mL, day 4-7) then fell (p <
      0.001, analysis of variance). Only IL-12 was higher in fracture patient plasma
      (1,279 +/- 602 pg/mL) than FxSTH serum (591 +/- 327 pg/mL) during the first 48
      hours (p = 0.032, U test). On flow cytometry, control monocytes expressed 201 +/-
      31 mTNF sites/cell, but icTNF was absent. mTNF was up-regulated after injury more
      in FxSTH monocytes (3,202 +/- 870 sites/cell) than peripheral blood monocytes
      (584 +/- 186 sites/cell) (p < 0.05 vs. peripheral blood monocytes by Wilcoxon, p
      < 0.001 vs. control monocytes by U test). Intracellular IL-10 was abundant in all
      MNC, but varied widely after injury. Fracture and peripheral blood monocytes
      expressed far less human leukocyte antigen-DR than control monocytes. Fractures
      create an inflammatory local environment. Proximal mediators are cell-associated
      and relatively confined to the wound, but soluble IL-6, IL-8, and IL-10 are
      abundant and probably exported. Systemic MNC have complex responses to local
      injuries. These may reflect the combined impact of multiple soluble cytokines
      initially generated within the wound. FxSTH appear to be a potentially important
      source of immunomodulatory cytokines in trauma.

PMID- 9191673
TI  - Acute management of complex cardiac injuries.
AB  - BACKGROUND: Injury to the heart has been studied extensively. However, a small
      group of patients with injuries to the coronary arteries or intracardiac
      structures may require a different operative approach. METHODS: Retrospective
      review of a cardiovascular injury database. RESULTS: Over a 20-year period, 711
      cardiac injuries were treated. The mean age of the victims was 31.1 (90% men).
      Causes were primarily stab wounds (54%) and gunshot wounds (42%). Cardiac
      chambers injured included the right ventricle (40%), left ventricle (40%), right
      atrium (24%), and left atrium (3%). The overall mortality was 47%. Sixty complex
      injuries occurred. Of 21 left anterior descending coronary artery injuries (76.2%
      mortality), two patients presented with sufficient signs of life to warrant
      emergent coronary artery bypass (mortality 50%). There were seven
      circumflex/obtuse marginal coronary artery injuries, all treated with ligation
      (mortality 71.4%). Eight right/posterior descending coronary artery injuries
      (mortality 62.5%) were seen, and all but one were treated with ligation. The one
      patient not treated with ligation underwent coronary bypass and died. Delayed
      mitral valve replacement was performed for two valvular injuries (mitral). There
      were a total of 14 intracardiac fistulas (mortality 35.7%). All six of the
      surviving patients with ventricular septal defect required reoperation.
      CONCLUSION: The mortality for complex injuries (coronary, septal, valvular) was
      53%. This group was a specific population that self-selected by surviving to
      operation. Acute operations for complex injuries (beyond cardiorrhaphy) were
      primarily heroic life-saving efforts. Reoperation for cardiac injuries was most
      common for septal or valvular injuries. Only 2% of all survivors required
      reoperation to correct a residual defect.

PMID- 9191675
TI  - Rehabilitation results of patients with multiple injuries and multiple organ
      failure and long-term intensive care.
AB  - BACKGROUND: Multiple organ failure is regarded to be the major complication of
      trauma victims treated in the intensive care unit. Long-term rehabilitation
      results of this special group of patients have not been analyzed so far. METHODS:
      Fifty patients with multiple injuries and multiple organ failure (Injury Severity
      Score > or = 36.8) were followed-up 4.9 +/- 0.3 years after the trauma. To show
      any organotopic sequelae, laboratory tests for the function of lungs, liver,
      kidney, and the hematologic system were performed. Additionally their functional
      (locomotion and neurologic system) and occupational rehabilitation results were
      investigated. RESULTS: The laboratory tests showed entirely normal results. The
      only pathologic values could be found in the lung function tests. Nineteen
      percent of the patients showed nonphysiologic results in either spirometry, body
      plethysmography, or diffusion capacity of carbon monoxide. In more than 25% of
      the patients, permanently decreased range of motion (limitation of more than 30%
      of the entire range of motion) of the elbow, hip, knee, or ankle joint were
      found. In 40% of the patients, permanent motoric nerve lesions were identified;
      in 50% of the patients, permanent sensoric nerve lesions could be verified. The
      return to work rate was 60%. CONCLUSIONS: Patients with multiple injuries, who
      survived multiple organ failure during their long-term intensive care treatment,
      show an excellent functional and occupational rehabilitation result. They show no
      major sequelae in their organ function even years after the trauma. Although
      often these patients suffer from permanent central or peripheral paralysis and
      decreased range of motion, this finding does not correlate with the patients'
      ability to return to work.

PMID- 9191674
TI  - Inferior vena cava injuries: noninvasive follow-up of venorrhaphy.
AB  - BACKGROUND AND METHODS: Recent reports have documented a reduced mortality from
      injuries to the inferior vena cava (IVC). Few reports, however, have addressed
      the follow-up of the repaired IVC. From January of 1984 to December of 1995, we
      prospectively collected data on all patients with IVC injuries at Lincoln Medical
      and Mental Health Center, an urban Level I trauma center. RESULTS: There were 81
      patients with IVC injuries: 60 gunshot wounds, 17 stab wounds, and four blunt
      injuries. Overall, 45 patients survived (56%). Excluding those who arrived
      without vital signs and those who did not have emergency department
      thoracotomies, the survival was 68%. Of the survivors, 38 patients received
      lateral venorrhaphy, and seven patients underwent ligation. Of the 38 survivors
      with lateral venorrhaphy, 30 patients (79%) underwent noninvasive follow-up: 13
      patients by sonography, 11 patients by computed tomographic scan, and six
      patients by both modalities. The IVC was visualized in 28 patients (93%) and was
      found to be patent in 24 (86%). There were four thromboses documented
      noninvasively, with three cases being confirmed by contrast venorrhaphy. All
      three resolved with systemic anticoagulation. CONCLUSIONS: We conclude that
      sonography and computed tomographic scan provide reliable noninvasive evaluation
      of the repaired IVC. We recommend that all patients with an IVC injury, which has
      been repaired, undergo evaluation for patency before discharge.

PMID- 9191676
TI  - Ax injuries of the hand.
AB  - OBJECTIVE: To review a series of ax injuries of the hand. DESIGN: Retrospective
      epidemiological review of 125 cases. MATERIALS: Assessment from the notes of all
      injuries, with more detailed follow-up of 26 cases. MEASUREMENTS: Levels of
      injury, surgery required, complications, results, patient satisfaction, methods
      of prevention. CONCLUSIONS: Ax injuries are rare. They usually affect the thumb
      and index finger of the nondominant hand. As with all hand injuries, expertise in
      dealing with bone, tendon, nerve, and skin cover is essential. Even "minor"
      injuries may give rise to considerable morbidity. Our complication rate in
      replantation was 50%. Care should be taken here not to compromise the result by
      attempting to maintain the length of the bony skeleton. The long-term results (at
      11 months to 12 years) were generally satisfactory, but cold intolerance may
      persist for many years. As with all accidents, prevention would be better than
      cure. Neither we nor the patients could think of any way of significantly
      reducing the incidence of these accidents. However, holding the ax by the neck
      seemed a common way of sustaining injury.

PMID- 9191677
TI  - Effects of an immune-enhancing diet in critically injured patients.
AB  - OBJECTIVE: To determine the effects of an immune-enhancing experimental diet (XD
      = supplemental arginine, trace elements, and increased omega-3 fatty acids)
      versus standard diet (SD), on immune cell function and clinical outcome of
      critically injured patients. DESIGN: Prospective randomized clinical trial of
      patients admitted to the surgical intensive care unit after trauma (Injury
      Severity Score > 13). MATERIALS AND METHODS: Patients received early enteral
      nutrition with either XD or SD for a minimum of 5 days. MEASUREMENTS: Mortality,
      intensive care unit, ventilator, and hospital days, as well as incidence of adult
      respiratory distress syndrome (ARDS) and infectious complications were recorded.
      Nutritional parameters were also studied. Peripheral blood leukocytes were
      isolated from normal volunteers and from patients on days 1, 6, and 10 of
      feeding. MAIN RESULTS: Demographics and injury severity were similar in both
      groups. Both SD (n = 21) and XD (n = 22) groups revealed depressed monocyte
      function (tumor necrosis factor, prostaglandin E2, and procoagulant activity) on
      day 1 compared with a reference group (p < 0.05). However, monocytes from XD
      patients began to "normalize" their response (tumor necrosis factor,
      prostaglandin E2, and procoagulant activity) by day 6. Although ARDS occurred
      more frequently in the XD group (45 vs. 19%), the majority of ARDS in both groups
      occurred very early, with only three patients in the XD (13.6%) and one patient
      in the SD (4.7%) groups developing ARDS after study entry. XD patients remained
      on the ventilator longer (16.4 vs. 9.7 days) and in the hospital longer (32.9 vs.
      22 days) compared with the SD group, but overall mortality was nearly identical
      (4.5 vs. 5%). CONCLUSION: The exact role and timing for diets with immune
      enhancing effects has yet to be defined.

PMID- 9191678
TI  - Reemployment of patients with surgical salvage of open, high-energy tibial
      fractures: an outcome study.
AB  - Between January 1, 1988, and December 31, 1990, 36 patients with 37 type III high
      energy open tibial shaft fractures were treated at Lehigh Valley Hospital.
      Patients with primary amputations were excluded. All patients with high-energy
      open tibial fractures with an intact posterior tibial nerve, protective
      sensations of the plantar surface of the foot, and warm ischemia time of less
      than 6 hours were considered salvageable. A retrospective review of the charts
      was completed. Twenty-eight patients with 29 fractures were interviewed for work
      status, an average of 39 months after treatment. Twenty-five patients with 25
      fractures were working at the time of the accident. Three patients with four
      fractures were not working at the time of the accident. Nineteen of 25 patients
      (76%) returned to work. Sixteen of 25 patients (64%) returned to work at a
      similar level of manual labor. The average delay between injury and return to
      work was 11 months (range, 3-18 months). Two of the 36 patients (5.5%) required
      secondary amputations. Twenty-five of 28 patients (89%) interviewed reported one
      or more subjective complaints. The two amputees reported no subjective
      complaints.

PMID- 9191680
TI  - Long-term outcome of isolated lesser tuberosity fractures of the humerus.
AB  - Ten cases of an isolated fracture of the lesser tuberosity and their long-term
      outcome are described. The patient ages at the time of injury ranged from 11 to
      68 years, averaging 30 years. In six cases, the injury was acute; in four cases,
      it had occurred more than 6 months previously. Of the six acute cases: three were
      treated conservatively, and the result was satisfactory for all of them; surgery
      was carried out in the other three cases, of which, two outcomes were judged to
      be excellent, and one outcome was satisfactory. Regarding the four chronic cases,
      muscle-strengthening exercises were given in two cases, whereas an operation was
      performed after exercise failed in the remaining two cases. The results of all
      four cases were graded as excellent. The combination of open reduction and
      internal fixation is the method most often recommended for acute cases. In
      chronic cases, conservative treatment is usually the most appropriate. However,
      when conservative treatment proves to be ineffective, then open reduction and
      internal fixation should be considered.

PMID- 9191679
TI  - Intramedullary pressure and bone marrow fat intravasation in unreamed femoral
      nailing.
AB  - OBJECTIVE: To investigate whether intramedullary pressure and bone marrow fat
      embolization are different in unreamed compared with conventional reamed femoral
      nailing. The null hypothesis is that there is no difference between the two
      techniques. DESIGN: A prospective consecutive nonrandomized clinical trial.
      METHODS: Intramedullary pressure was measured in the distal femoral fracture
      fragment at the supracondylar region. Bone marrow fat intravasation was measured
      by means of the modified Gurd-test. Monitoring was carried out in 31 unreamed and
      eight reamed intramedullary femoral nailing procedures. RESULTS: Intramedullary
      pressure increased in the unreamed group to 82 +/- 11 mm Hg during the insertion
      of 9-mm and 10-mm nails and in the reamed group to 396 +/- 85 mm Hg during
      reaming of the medullary cavity. Insertion of nails after reaming led to an
      increase in intramedullary pressure of 79 +/- 13 mm Hg. A positive correlation
      between fat intravasation and intramedullary pressure was found in each group (rs
      = 0.73), resulting in less liberation of bone marrow fat in the unreamed group
      than in the reamed group. CONCLUSIONS: Intramedullary pressure increased
      significantly in the reamed more than in the unreamed group. Bone marrow fat
      intravasation depended on the rise in intramedullary pressure, and occurred less
      frequently in unreamed than in reamed intramedullary femoral fracture
      stabilization.

PMID- 9191681
TI  - Limitations of transesophageal echocardiography for the diagnosis of traumatic
      injuries to aortic branches.

PMID- 9191682
TI  - Multimodality treatment for grade V hepatic injuries: perihepatic packing,
      arterial embolization, and venous stenting.

PMID- 9191683
TI  - Assessment of blunt aortic-brachiocephalic trauma: should angiography be
      supplanted by transesophageal echocardiography?

PMID- 9191684
TI  - Pulmonary contusion: review of the clinical entity.
AB  - Pulmonary contusion is a common lesion occurring in patients sustaining severe
      blunt chest trauma. Alveolar hemorrhage and parenchymal destruction are maximal
      during the first 24 hours after injury and then usually resolve within 7 days.
      The diagnosis of traumatic lung injury is usually made clinically with
      confirmation by chest x-ray films. The chest computed tomography scan is highly
      sensitive in identifying pulmonary contusion and may help predict the need for
      mechanical ventilation. Respiratory distress is common after lung trauma, with
      hypoxemia and hypercarbia greatest at about 72 hours. Although management of
      patients with pulmonary contusion is supportive, pneumonia and adult respiratory
      distress syndrome with long-term disability occur frequently.

PMID- 9191685
TI  - Internal fixation in pelvic fractures and primary repairs of associated
      genitourinary disruptions: a team approach.

PMID- 9191686
TI  - Early fracture fixation may be deleterious after head injury.

PMID- 9191687
TI  - Early fracture fixation may be deleterious after head injury.

PMID- 9191688
TI  - Early fracture fixation may be deleterious after head injury.

PMID- 9191689
TI  - Avoidance of hypotension: conditio sine qua non of successful severe head-injury
      management.

PMID- 9191691
TI  - Guidelines for the management of severe head injury: what we know and what we
      think we know.

PMID- 9191690
TI  - Therapy of patients with head injuries: key parameters for management.
AB  - BACKGROUND: Secondary brain injury, presumed secondary to ischemia, increases the
      mortality and morbidity of traumatic brain injury. Although many mechanisms
      appear to be involved, many potential ischemic insults results from changes in
      readily observable physiologic variables. METHODS: A focused search of scientific
      articles published in English to determine what data are available to suggest
      parameters within which key physiologic variables should be maintained. RESULTS:
      Few data demonstrate that maintenance of variables within specific ranges alters
      outcome; however, considerable evidence establishes association with poor outcome
      and hypotension, intracranial hypertension, and cerebral venous saturation. Key
      parameters vary somewhat based upon the phase of treatment after injury. Other
      variables, such as systemic oxygen delivery and brain saturation measured by near
      infrared spectroscopy, are less well linked to outcome. CONCLUSIONS: Further
      research is necessary to establish that manipulation of physiologic variables to
      maintain them within preset ranges improves outcome.

PMID- 9191692
TI  - Physiologic principles for volume regulation of a tissue enclosed in a rigid
      shell with application to the injured brain.
AB  - BACKGROUND: Preservation of a high cerebral perfusion (mean arterial) pressure to
      prevent ischemia has become the primary focus during treatment of severe head
      trauma because ischemia is favored as a triggering mechanism behind intracellular
      brain edema development and poor outcome. A high cerebral perfusion pressure,
      however, simultaneously may increase the hydrostatic vasogenic edema. The present
      paper evaluates the mechanisms behind the vasogenic edema by analyzing the
      physiologic hemodynamic mechanisms controlling the volume of a tissue that is
      enclosed in a rigid shell, possesses capillaries permeable for solutes, and has
      depressed autoregulation. RESULTS AND CONCLUSIONS: We contend that in the long
      run, the interstitial volume in such a tissue can be reduced only through
      reduction in arterial inflow pressure providing an otherwise optimal therapy to
      improve microcirculation. Therefore we argue, in contrast to the conventional
      view, that antihypertensive and antistress therapy may be of value by reducing
      the interstitial tissue volume during treatment of brain edema, and that the
      problem with ischemia during such therapy can be handled when considering an
      otherwise optimal intensive care. These physiologic principles of interstitial
      tissue volume regulation form the basic concept for the "Lund therapy" of severe
      head injuries, which is a new and controversial therapy of posttraumatic brain
      edema.

PMID- 9191693
TI  - Multimodal monitoring in patients with head injury: evaluation of the effects of
      treatment on cerebral oxygenation.
AB  - BACKGROUND: Recently, invasive intensive care unit monitoring of cerebral
      oxygenation has become feasible. The purpose of this study was to investigate the
      effects of standard therapeutic interventions used in the treatment of
      intracranial hypertension on cerebral oxygenation and other physiologic
      parameters in comatose patients. METHODS: In the neurosurgical intensive care
      unit, Ptio2, and jugular bulb oxygen saturation (Sjvo2), arterial blood pressure,
      intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were
      prospectively studied (0.1 Hz acquisition rate) with a multimodal monitoring
      system in 21 patients with severe traumatic brain injury during various treatment
      modalities: dopamine and mannitol infusion, head positioning, and induced
      arterial hypocapnia. RESULTS: For baseline CPP values below 40 mm Hg, dopamine
      infusion was more effective in decreasing ICP and improving Ptio2 and Sjvo2 than
      for initial CPP values above 60 mm Hg. Treatment with mannitol, although
      improving CPP and lowering ICP, did not affect Ptio2 and Sjvo2. CPP in this
      group, however, was always above 60 mm Hg. Forced hyperventilation to an end
      tidal Pco2 of 21 mm Hg normalized ICP and CPP, but significantly reduced cerebral
      oxygenation. CONCLUSION: A CPP > 60 mm Hg emerges as the crucial factor
      guaranteeing sufficient brain oxygenation. Any intervention used to further
      elevate CPP does not improve cerebral oxygenation, to the contrary, forced
      hyperventilation even bears the risk of inducing brain ischemia.

PMID- 9191694
TI  - Endothelial cell swelling and brain perfusion.
AB  - BACKGROUND: Whereas the contribution of glial swelling to no-reflow conditions in
      the ischemic penumbra or during reperfusion after after global ischemia is widely
      discussed, little is known about cell volume control of endothelial cells under
      reperfusion conditions. METHODS: The effect of extracellular acidosis-a key
      mediator of secondary brain damage-on cell volume was studied in the GM7373
      endothelial cell line. Experiments were performed at pH = 6.0 in the presence or
      absence of bicarbonate, and during exposure to inhibitors of specific transport
      systems such as ethyl isopropyl amiloride or 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid. RESULTS: Endothelial swelling to 111.1 +/- 3.4% was found at pHe
      = 6.0 in bicarbonate-buffered media. In hydroxyethyl piperin ethanesulfonic acid
      buffered media, swelling was only 107.9 +/- 0.3%. 4,4'-Diisothiocyanatostilbene
      2,2'-disulfonic acid reduced swelling to 102.8 +/- 0.6% in bicarbonate media,
      whereas swelling was completely prevented in the presence of ethyl isopropyl
      amiloride in hydroxyethyl piperin ethanesulfonic acid-buffered media.
      CONCLUSIONS: Endothelial swelling can be expected to occur in severely ischemic
      tissue sections and may then advance no-reflow. Therapeutic strategies should be
      established to prevent acidosis-induced endothelial swelling, e.g., by specific
      antagonists of the transport systems involved, or to reduce swelling by osmotic
      treatment such as hypertonic-hyperoncotic solutions.

PMID- 9191695
TI  - Hypertonic/hyperoncotic saline attenuates microcirculatory disturbances after
      traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) induces an acute inflammatory response
      characterized by early recruitment of inflammatory cells (white blood cells).
      Rapid resuscitation of TBI with hypertonic saline/dextran (HS/DEX) yields
      promising results in clinical and experimental studies. The purpose of this paper
      was to test the hypothesis that HS/DEX exerts its effects in part through a
      modulation of the acute inflammatory response to TBI. METHODS: Rabbits equipped
      with chronic cranial windows underwent fluid-percussion injury and were followed
      up for 6 hours. Intravital fluorescence videomicroscopy technique was used to
      visualize white blood cell trafficking and to measure pia vessel diameters and
      venular shear rates. Three groups were studied: sham (group I, n = 5), trauma
      (group II, n = 7), and trauma and 4 mL/kg 7.2% NaCl/10% dextran 60 IV over 5
      minutes at 10 minutes after TBI (group III, n = 7). RESULTS: TBI in groups II and
      III led to significant increases of intracranial pressure. Arteriolar diameters
      after trauma increased by 17 +/- 8% at 6 hours in group II. Infusion of HS/DEX
      completely prevented this secondary diameters increase. At 6 hours, the increase
      of "sticking" white blood cells in group III was reduced by approximately 90%
      compared with group II. CONCLUSIONS: Whether the anti-inflammatory effect of
      HS/DEX plays a role in reducing delayed brain damage (> 6 hours after TBI) or
      other systemic complications of TBI arises as an important question and should be
      investigated further.

PMID- 9191696
TI  - Effect of small-volume resuscitation on intracranial pressure and related
      cerebral variables.
AB  - BACKGROUND: Head injury outcome is adversely affected by the presence of
      hypotension. Therapies directed at rapidly correcting hypotension may improve
      outcome. METHODS: In two separate studies, we investigated small-volume
      resuscitation (4 mL/kg) using Ringer's lactate, hypertonic saline and dextran,
      and diaspirin cross-linked hemoglobin in a porcine model of cryogenic brain
      injury and shock. RESULTS: Small-volume resuscitation with hypertonic saline and
      dextran and diaspirin cross-linked hemoglobin significantly improved mean
      arterial pressure and cerebral perfusion pressure compared with Ringer's lactate.
      These data suggest that small-volume resuscitation with hypertonic saline and
      dextran or diaspirin cross-linked hemoglobin may effectively limit or prevent
      secondary ischemic brain injury after head injury and shock.

PMID- 9191697
TI  - Hypertonic saline administration attenuates spinal cord injury.
AB  - BACKGROUND: This manuscript describes the results of three studies designed to
      test the hypothesis that the intravenous administration of hypertonic saline
      could help to preserve spinal cord function after injury. METHODS: A static
      compression model was used to injure rat spinal cords. Somatosensory evoked
      potentials and spinal cord blood flow changes were monitored in the acute
      studies. The first study compared the effects of administration of hypertonic
      saline with isotonic saline solutions. The second study evaluated the effect of
      hypertonic saline administration at 5, 15, and 60 minutes after injury. A chronic
      injury model was evaluated in the third study. Spontaneous voiding, neurologic
      function, and evidence of histologic changes were evaluated. RESULTS AND
      CONCLUSIONS: The administration of hypertonic saline after spinal cord injury
      increased blood flow and helped preserve spinal cord function in the acute
      models. The rate of recovery with the chronic model was significantly faster in
      hypertonic saline treated animals.

PMID- 9191698
TI  - Individual patient cohort analysis of the efficacy of hypertonic saline/dextran
      in patients with traumatic brain injury and hypotension.
AB  - BACKGROUND: Resuscitation with hypertonic saline/dextran (HSD) has been suggested
      to be efficacious in patients who have traumatic brain injury and are
      hypotensive. We undertook a cohort analysis of individual patient data from
      previous prospective randomized double-blinded trials to evaluate improvements in
      survival at 24 hours and discharge after initial treatment with HSD in patients
      who had traumatic brain injury (head region Abbreviated Injury Score > or = 4)
      and hypotension (systolic blood pressure < or = 90 mm Hg). METHODS: All variables
      and end points were defined before initiation of data handling. Investigators
      were blind as to the treatment. Case report forms were received from six studies.
      Of these, 223 patients met the inclusion for traumatic brain injury. Comparisons
      between HSD and standard of care were made using stratified analysis and logistic
      regression to assess efficacy, confounding, and interaction. Potential
      confounding variables of pre-fluid treatment, Glasgow Coma Scale score (3-8 vs. 9
      15), injury type, and systolic blood pressure can be considered a priori factors
      that were known before randomization. Effects of the various trials was also
      considered. RESULTS: Treatment with HSD resulted in a survival until discharge of
      37.9% (39 of 103) compared with 26.9% (32 of 119) with standard of care (p =
      0.080). Using logistic regression, adjusting for trial and potential confounding
      variables, the treatment effect can be summarized by the odds ratio of 2.12 (p =
      0.048) for survival until discharge. CONCLUSIONS: Patients who have traumatic
      brain injuries in the presence of hypotension and receive HSD are about twice as
      likely to survive as those who receive standard of care.

PMID- 9191699
TI  - Management of patients with severe head injury in the preclinical phase: a
      prospective analysis.

PMID- 9191701
TI  - Research without billing data. Econometric estimation of patient-specific costs.
AB  - OBJECTIVES: This article describes a method for computing the cost of care
      provided to individual patients in health care systems that do not routinely
      generate billing data, but gather information on patient utilization and total
      facility costs. METHODS: Aggregate data on cost and utilization were used to
      estimate how costs vary with characteristics of patients and facilities of the US
      Department of Veterans Affairs. A set of cost functions was estimated, taking
      advantage of the department-level organization of the data. Casemix measures were
      used to determine the costs of acute hospital and long-term care. RESULTS:
      Hospitalization for medical conditions cost an average of $5,642 per US Health
      Care Financing Administration diagnosis-related group weight; surgical
      hospitalizations cost $11,836. Nursing home care cost $197.33 per day,
      intermediate care cost $280.66 per day, psychiatric care cost $307.33 per day,
      and domiciliary care cost $111.84 per day. Outpatient visits cost an average of
      $90.36. These estimates include the cost of physician services. CONCLUSIONS: The
      econometric method presented here accounts for variation in resource use caused
      by casemix that is not reflected in length of stay and for the effects of medical
      education, research, facility size, and wage rates. Data on non-Veteran's Affairs
      hospital stays suggest that the method accounts for 40% of the variation in acute
      hospital care costs and is superior to cost estimates based on length of stay or
      diagnosis-related group weight alone.

PMID- 9191700
TI  - Clinical quality measurement. Comparing chart review and automated methodologies.
AB  - OBJECTIVES: This study investigates the use of data from automated systems within
      a large managed care plan to create indicators of clinical quality. METHODS:
      Measures from the first year of Health Plan Employer Data and Information Set,
      HEDIS 2.0, are used to compare chart review and automated analysis methodologies.
      The contributions of various data systems in creating clinical quality measures
      are evaluated. RESULTS: Chart review data usually are better for creating
      clinical quality indicators, although the level of agreement between the two
      methodologies often is quite high. Computerized patient record systems are found
      to be the most reliable automated data source, and automated claims are found to
      be the least reliable. This study's findings suggest that automated encounter
      systems may provide relatively reliable data. CONCLUSIONS: Managed care plans may
      not want to rely on automated data alone for clinical quality measurement. The
      results reported here support the use of combined methodologies such as the
      "hybrid" method, which utilizes both automated and chart-review data.

PMID- 9191702
TI  - Family care in the United States. A national profile.
AB  - OBJECTIVES: The authors describe the epidemiology of family care in the United
      States. METHODS: A cross-sectional analysis of data from the household component
      of the 1987 National Medical Expenditure Survey was performed. A representative
      sample of the civilian, noninstitutionalized US population was analyzed.
      Participants in the study were all households with at least a mother between the
      ages of 18 and 55 years and at least one child younger than age 18 (n = 2,975).
      For this analysis, family care was defined as all families in which there was
      provider congruence between at least one parent and one child, compared with
      individual care, defined as families with separate providers. RESULTS: Family
      care occurred in 35% of families studied. As opposed to individual care, family
      care was more prevalent in families that resided in non-standard metropolitan
      statistical area regions and outside of the Northeast, as well as in families
      whose female heads of household were less educated, older, and had higher
      unhealthy behavior scores. Except for unhealthy behavior scores, these results
      remained significant after multivariate adjustment for race, marital status,
      family income, insurance status, and health care attitudes. Family or general
      practitioners were more likely than other physicians to provide family care.
      CONCLUSIONS: Family care occurs in a significant proportion of US families, and
      location and education are significant determinants of this kind of care. This
      descriptive epidemiologic analysis of a nationally representative sample provides
      a foundation for studies examining the cost and quality implications of family
      care.

PMID- 9191703
TI  - The effect of certificate of need and moratoria policy on change in nursing home
      beds in the United States.
AB  - OBJECTIVES: This study examined the effects of state certificate of need and/or
      moratorium requirements on the change in nursing home bed growth in states over a
      13-year period. METHODS: Data were collected from five telephone surveys of state
      officials about state certificate of need and moratorium policies, state Medicaid
      nursing home reimbursement rates, and the licensed nursing home beds in each
      state for the 1979 through 1993 period. Two-stage least squares regression
      analysis treated certificate of need and/or moratorium and Medicaid reimbursement
      rates as endogenous variables in predicting the change in nursing home beds per
      aged population in states. RESULTS: States that had a certificate of need and/or
      moratorium did have significant reductions in the growth in nursing home beds but
      Medicaid nursing home reimbursement rates were not related to change in bed
      stock. The percentage of the population living in a metropolitan area, the
      personal income per 1,000 population, the percent unemployed, a state's tax
      effort, and time were positively associated with change in nursing home beds. The
      ratio of nursing home beds per 1,000 aged population in the previous year was a
      negative predictor of change in bed stock in a given year. CONCLUSIONS: State
      regulatory policies have an effect on bed growth in contrast to reimbursement
      policies.

PMID- 9191704
TI  - International Classification of Diseases, 9th Revision, Clinical Modification
      codes in discharge abstracts are poor measures of complication occurrence in
      medical inpatients.
AB  - OBJECTIVES: The authors tested the ability of International Classification of
      Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes in discharge
      abstracts to identify medical inpatients who experienced an in-hospital
      complication, using complications identified through chart review as the gold
      standard. METHODS: Two sets of ICD-9-CM codes were used: an inclusive set
      including many medical diagnoses that may also be coexistent complicating
      conditions on admission rather than complications and an exclusive set consisting
      primarily of ICD-9-CM-specified complication and adverse drug event codes.
      RESULTS: Neither set performed well as a diagnostic test for complication
      occurrence according to receiver operating characteristic analysis (ROC areas
      were 0.61 for the inclusive set and 0.55 for the exclusive set). Sensitivities of
      the ICD-9-CM codes for complications were 0.34 for the inclusive set and 0.14 for
      the exclusive set. Corresponding positive predictive values were 0.32 and 0.37,
      respectively. Sensitivities of code definitions for individual complications were
      generally poor, less than 0.5 in most cases. CONCLUSIONS: The authors conclude
      that ICD-9-CM codes in discharge abstracts are poor measures of complication
      occurrence.

PMID- 9191705
TI  - Physicians' judgments of the risks of cardiac procedures. Differences between
      cardiologists and other internists.
AB  - OBJECTIVES: The authors compared judgments of the population risks of invasive
      cardiac procedures made by cardiologists and other internal medicine physicians.
      Our main hypotheses were that cardiologists' judgments would differ from those
      made by the other physicians and that cardiologists' judgments would be more
      accurate than those of other physicians. METHODS: This was a cross-sectional
      survey of senior staff and physician-trainees at two teaching hospitals
      affiliated with a US medical school, Emergency Department physicians at a
      community hospital in the same metropolitan area, and senior staff and trainees
      at two teaching hospitals affiliated with a UK school. Judgments of the risks of
      severe morbidity and death due to Swan-Ganz catheterization, cardiac
      catheterization, percutaneous coronary angioplasty, and coronary artery bypass
      grafting were assessed. RESULTS: Nineteen cardiologists judged the risks of
      severe morbidity due to all procedures and the risks of death due to all
      procedures except coronary artery bypass grafting to be significantly lower than
      did the 78 other internists. Cardiologists more frequently made accurate
      judgments of the rates of morbidity and death due to cardiac catheterization than
      did the other internists; other internists more frequently made accurate
      judgments for the rates of morbidity due to Swan-Ganz catheterization.
      CONCLUSIONS: Disagreements about the risks of procedures may arise from a paucity
      of published data, or from an over-supply of confusing data.

PMID- 9191706
TI  - Understanding the state variation in Medicare home health care. The impact of
      Medicaid program characteristics, state policy, and provider attributes.
AB  - OBJECTIVES: During the past 7 years there has been a significant increase in the
      use of the Medicare home health benefit. In this article, the authors document
      trends in the use of the benefit and develop multivariate models to identify the
      factors that explain state variation in its use. METHODS: To develop quantitative
      models, the authors collected state information on all variables for each of 3
      years: 1991, 1992, and 1993. The authors chose to focus on those variables that
      had been found to be significant in other research as well as those that we
      posited would likely influence utilization. The authors tested similar sets of
      explanatory variables for each year of the analysis. The unit of analysis is the
      "state" and depending on data availability, the number of states included in the
      analyses range from between 46 to 49. (Arizona does not have a state Medicaid
      program.) RESULTS: The authors' analysis shows that interaction exists between
      state policies and use of the benefit. Utilization is higher in states that face
      greater fiscal pressure concerning their Medicaid budgets; the lack of state
      personal care programs increases Medicare use, and, when Medicaid home health
      expenditures decline, the number of Medicare home health care users increases.
      There is also an inverse relationship between the number of long-term care and
      skilled nursing facilities in a state and the use of the benefit. Thus, for some,
      the benefit serves as a substitute for long-term care needs and, for others, for
      postacute care needs. CONCLUSIONS: The overlap between the population served and
      the services provided by state programs and Medicare has given states and
      providers an opportunity to leverage Federal dollars in lieu of state program
      dollars. As the Federal government attempts to control expenditure growth, policy
      makers must be mindful of how state actions can influence the level and type of
      Federal expenditure.

PMID- 9191707
TI  - The effects of health care reforms on job satisfaction and voluntary turnover
      among hospital-based nurses.
AB  - OBJECTIVES: Among the consequences of downsizing and cost containment in
      hospitals are major changes in the work life of nurses. As hospitals become
      smaller, patient acuity rises, and the job of nursing becomes more technical and
      difficult. This article examines the effects of changes in the hospital
      environment on nurses' job satisfaction and voluntary turnover between 1993 and
      1994. METHODS: Data were collected in a longitudinal survey of 736 hospital
      nurses in one hospital to examine correlates of change in aspects of job
      satisfaction and predictors of leaving among nurses who terminated in that
      period. RESULTS: Unadjusted results showed decline in most aspects of
      satisfaction as measured by Hinshaw and Atwood's and Price and Mueller's scales.
      Multivariate analysis indicated that the most important determinants of low
      satisfaction were poor instrumental communication within the organization and too
      great a workload. Intent to leave was predicted by the perception of little
      promotional opportunity, high routinization, low decision latitude, and poor
      communication. Predictors of turnover were fewer years on the job, expressed
      intent to leave, and not enough time to do the job well. CONCLUSIONS: The authors
      conclude that although many aspects of job satisfaction are diminished, some
      factors predicting low satisfaction and turnover may be amenable to change by
      hospital administrators.

PMID- 9191708
TI  - An evaluation of the impact of nonresponse bias on patient satisfaction surveys.

PMID- 9191710
TI  - Boston Working Group on Improving Health Care Outcomes Through Geriatric
      Rehabilitation.
AB  - Geriatric rehabilitation is a multidisciplinary set of evaluative, diagnostic,
      and therapeutic interventions whose purpose is to restore functional ability or
      enhance residual functional capability in elderly people with disabling
      impairments. The Boston Working Group on Improving Health Care Outcomes Through
      Geriatric Rehabilitation was convened to begin a dialogue among experts in
      rehabilitation, quality of care, and health services research to consider ways to
      measure, improve, and ensure the quality of geriatric rehabilitation services.
      The conference centered around four major themes: the definition of
      disability/disablement; the patient's experience of rehabilitative care; the role
      of clinical practice guidelines; and the need for casemix and severity or risk
      adjustment procedures and measures. The plenary speaker discussed potential new
      directions in each of these areas and reviewed the contribution of these
      innovations to improved means of outcomes assessment. Each of the four themes was
      addressed in the form of a paper by an expert in the field. Two reactors with
      different viewpoints responded to these papers, and small working groups of
      participants, convened by topic, contributed to discussions later summarized and
      presented in plenary session by a spokesperson for each group. In one small
      group, two reporters represented the majority and minority opinions. A summary
      speaker presented an overview of the conference deliberations and focused on four
      of the critical points raised by the working groups: (1) the need to define and
      describe geriatric rehabilitation in lay terms; (2) the need for more research to
      link process with outcome; (3) the need to balance long-term measurement of
      process and outcome with short-term analysis that facilitates creative response
      to accelerating changes in the health care sector; and (4) the need to convince a
      diverse audience of the role of geriatric rehabilitation in providing high
      quality care, good health status, and functional outcomes for older patients.

PMID- 9191711
TI  - Improving outcomes in rehabilitation. A call to arms (and legs).
AB  - In rehabilitation, assessment of outcomes requires refinement of existing
      measurement and analysis tools. A suitable taxonomy of outcomes, risk factors,
      and treatment modalities must be developed to reflect the field's complexity and
      the multiplicity of care providers. The goal of outcomes studies is to
      distinguish the effects of treatment from improvement resulting from the natural
      course of illness. Outcomes researchers must adjust for casemix and be alert to
      possible selection effects. A common set of outcome measures is needed to measure
      disability. Those currently in use reflect both nursing home and rehabilitation
      care. They rely on provider information and measure patients' performance, but
      they do not record patients' perceptions of important components of outcomes.
      Current techniques for describing treatment are inadequate. Outcomes assessment
      must include adjustment for prognostic factors and must be measured against
      baseline information at the onset of treatment. Although patients' perception of
      care is recognized as important to outcomes assessment, patients should also play
      a central role in decision-making about care and in weighting the importance of
      the various outcomes. In an era of managed care, the major challenge for
      rehabilitation care is to demonstrate its cost-effectiveness. Clear and precise
      analysis of the salient issues and a dynamic model of outcomes measurement will
      facilitate this goal and will permit incorporation of new learning in this field.

PMID- 9191712
TI  - Disablement outcomes in geriatric rehabilitation.
AB  - Until recently, knowledge in the field of geriatric rehabilitation has been based
      largely on empirical findings. There is a need for greater conceptual clarity
      about major disablement outcomes to provide a foundation for future theoretical
      research. Disablement terms promulgated by the World Health Organization's (WHO)
      International Classification of Impairments Disabilities and Handicaps (ICIDH)
      are reviewed and compared with those of an alternative model proposed by Saad
      Nagi in 1965. Distinctions are drawn between the disablement concepts each system
      includes to refer to (1) inherent attributes of patients and (2) the interaction
      of the patient with the social and physical environment. The importance of a
      disablement model reflecting this distinction between inherent and relational
      concepts is emphasized. Areas for fertile research opportunities in which the
      disablement concepts could be used are discussed. It is suggested that improved
      understanding of disablement outcomes could be most readily achieved by
      application of an epidemiologic model separating the factors affecting outcomes
      into three sets of variables: the host factors representing intra-individual
      attributes; the agent factors, which are the external event or events causing the
      disability; and the environmental factors, which relate to the physical or social
      surroundings in which the disability occurs. In future research efforts, a more
      theoretical approach to studying disablement outcomes is advocated as a basis for
      improvements in geriatric rehabilitation.

PMID- 9191713
TI  - Disablement outcomes in geriatric rehabilitation. Report: Group D.

PMID- 9191714
TI  - Rehabilitation care and outcomes from the patient's perspective.
AB  - In the past, quality of health care was measured principally with reference to
      provider-established norms. More recently, increased attention has been paid to
      patients' views on care delivery and outcomes. However, in rehabilitation
      medicine, this trend has not been established: provider-assessed outcomes during
      short stays in specific settings are the focus of care. This article offers a
      theoretic framework for the assessment of rehabilitative care from the patient's
      perspective. Four domains of the patient's experience and the specific dimensions
      of each domain are discussed, and their influence on the measurement of quality
      from the patient's viewpoint is reviewed. A similar comparison is made between
      patient and provider perspectives on care outcomes. Examples are provided of
      patient-based outcome measures. Emphasis is placed on the importance of
      distinguishing between provider and patient perspectives and on giving the
      patient's views a primary role in evaluating care and outcomes.

PMID- 9191715
TI  - Rehabilitation care and outcomes from the patient's perspective. Report: Group E.

PMID- 9191716
TI  - Can clinical practice guidelines increase the cost-effectiveness of geriatric
      rehabilitation?
AB  - The need for guidelines stems from the human and economic burdens of
      disabilities, from variations in practice patterns, and from controversy over the
      effectiveness of rehabilitation. This article describes the development of the
      stroke rehabilitation guidelines and highlights several recommendations that have
      implications for geriatric rehabilitation more generally. It then describes a
      pilot test of resulting review criteria and a study in progress that is examining
      the extent to which rehabilitation referrals after acute strokes follow guideline
      recommendations. Finally, it closes by underscoring several policy challenges
      that will be critical to achieving more cost-effective use of rehabilitation
      resources.

PMID- 9191717
TI  - Can clinical practice increase the cost-effectiveness of geriatric
      rehabilitation? Small Work Group majority report.

PMID- 9191718
TI  - Can clinical practice guidelines increase the cost-effectiveness of geriatric
      rehabilitation? Small Work Group minority report.

PMID- 9191719
TI  - Measuring casemix, severity, and complexity in geriatric patients undergoing
      rehabilitation.
AB  - Geriatric rehabilitation is intended to maintain or restore function, maximize
      life satisfaction, enhance psychologic well-being, and maintain the social status
      of older persons. For clinical services to operate efficiently and equitably,
      payment must be based on rules that are clinically sound and thus reinforce the
      objectives of the services provided. This article presents a theoretical basis
      for casemix measurement in medical rehabilitation, contrasts structure of the
      functional independence measure-function-related groups (FIM-FRGs) intended for
      casemix measurement to the diagnosis-related groups (DRGs) and resource
      utilization groups (RUG) III systems designed for acute and long-term care
      settings, focuses on special issues of relevance to the rehabilitation of older
      persons, and provides four challenges in an effort to stimulate discussion.

PMID- 9191720
TI  - Measuring casemix, severity, and complexity in geriatric patients undergoing
      rehabilitation. Small Work Group I report.

PMID- 9191721
TI  - Measuring casemix, severity, and complexity in geriatric patients undergoing
      rehabilitation. Small Work Group II report.

PMID- 9191722
TI  - Improving health care outcomes through geriatric rehabilitation. Conference
      summary.
AB  - The Boston Working Group on Improving Health Care Outcomes Through Geriatric
      Rehabilitation was structured around four major themes: (1) defining disability
      or disablement; (2) the patient's experience of the processes and outcomes of
      care; (3) the role and value of clinical practice guidelines; and (4) the need
      for casemix and severity or risk adjustment procedures and measures. These
      discussions produced opening statements of policy or empiric issues and
      recommendations about the best means of demonstrating the benefits of geriatric
      rehabilitation and, in particular, how to measure, ensure, and improve the
      quality of rehabilitation services, especially for the elderly. This article
      summarizes the reports from the work groups and identifies some common themes.
      Critical points include: (1) the need to define and describe geriatric
      rehabilitation better for nonexperts in the health field and for patients and
      consumers in general; (2) the need for more research to link rehabilitation
      processes with measurable and clinically important outcomes; (3) the breadth and
      depth of domains of processes and outcomes of care that ideally could and should
      be measured; and (4) the need to reach many audiences with a clear message about
      the importance of geriatric rehabilitation in ensuring high quality of care and
      good health status and functional outcomes for all elderly patients.

PMID- 9191723
TI  - Services for epilepsy in the United Kingdom.

PMID- 9191724
TI  - Patterns of epilepsy care in Japan.

PMID- 9191725
TI  - Perspectives on epilepsy care in Denmark.

PMID- 9191726
TI  - Perspectives of epilepsy care in Norway.

PMID- 9191727
TI  - Epilepsy care in Germany: a clinical perspective.

PMID- 9191728
TI  - Patterns of care for patients with epilepsy in France.

PMID- 9191729
TI  - Perspectives of epilepsy care in the United States: children and the
      developmentally disabled.

PMID- 9191730
TI  - Care of adults with epilepsy in the United States.

PMID- 9191731
TI  - Helicobacter pylori-associated gastroduodenal disease in childhood.
AB  - Helicobacter pylori is responsible for one of the most frequently encountered
      infectious diseases worldwide. Infection due to H pylori can lead to the
      development of gastritis and peptic ulcer disease. The presence of H pylori in
      the human stomach also represents an increased risk for gastric cancer and
      gastric lymphoma. Recent epidemiologic data obtained in adults suggest that the
      actual colonization with H pylori is in fact determined by childhood factors.
      Therefore, the pediatric age group represents the ideal target population for
      studies concerning the pathogenesis and epidemiology of H pylori infection. This
      review addresses the spectrum of H pylori-associated gastroduodenal disease in
      childhood.

PMID- 9191732
TI  - Roles of mental health professionals in multidisciplinary medically supervised
      treatment programs for obesity.
AB  - Excess weight is a major medical problem for more than one third of Americans
      and, after cigarette smoking, is the second largest cause of death. However,
      obesity treatments remain controversial, and only surgical therapies have patient
      volume and appropriate follow-up adequate to prove effectiveness. National
      Institutes of Health conferences on obesity treatments and the Institute of
      Medicine have suggested that all obesity treatment programs, including those
      which are medically supervised, should be multidisciplinary, involving
      professionals from the behavioral, nutritional, and exercise fields to facilitate
      delivery of a patient-treatment matching strategy. There are no models to suggest
      how these recommendations should be accomplished or whether they are financially
      feasible. We present a case management model that includes psychotherapists in a
      multidisciplinary obesity treatment program. More data are needed to show whether
      these suggestions improve cost-effectiveness of obesity treatments.

PMID- 9191734
TI  - The culture of morning report: ethnography of a clinical teaching conference.
AB  - We studied the structure, process, and subjective meaning of "morning report," a
      time-honored, medical teaching conference attended by faculty, house officers,
      and students at a pediatric teaching hospital. Methods included participant
      observation, focused interviews, and content analyses. Results showed substantial
      variation by rank in behavior, perception, and participation based on a highly
      structured division of labor. The most frequent suggestion for improving morning
      report was to shorten it. Data indicate that morning report, at least at our
      study site, is out of step with current learner-centered models, seems
      perfunctory, and may be costly in the current climate of decreased revenues and
      downsizing. The persistence of morning report, despite these liabilities, attests
      to its significance as a cultural event.

PMID- 9191733
TI  - Sarin poisoning on Tokyo subway.
AB  - On the day of the disaster, 641 victims were seen at St. Luke's International
      Hospital. Among those, five victims arrived with cardiopulmonary or respiratory
      arrest with marked miosis and extremely low serum cholinesterase values; two died
      and three recovered completely. In addition to these five critical patients, 106
      patients, including four pregnant women, were hospitalized with symptoms of mild
      to moderate exposure. Other victims had only mild symptoms and were released
      after 6 hours of observation. Major signs and symptoms in victims were miosis,
      headache, dyspnea, nausea, ocular pain, blurred vision, vomiting, coughing,
      muscle weakness, and agitation. Almost all patients showed miosis and related
      symptoms such as headache, blurred vision, or visual darkness. Although these
      physical signs and symptoms disappeared within a few weeks, psychologic problems
      associated with posttraumatic stress disorder persisted longer. Also, secondary
      contamination of the house staff occurred, with some sort of physical abnormality
      in more than 20%.

PMID- 9191736
TI  - Neurologic and neuropsychiatric complications of Crohn's disease.
AB  - The literature contains sporadic accounts of neurologic complications occurring
      in patients with Crohn's Disease (CD). The pathogenesis of these is unknown and
      little has been reported about their incidence. Our review of the medical records
      of 253 patients with confirmed CD showed that neurologic and neuropsychiatric
      complications were evident in 84 of the patients, an incidence of 33.2%. In some
      the association could be casual, but in others the incidence of such
      complications was higher than that in the general population, suggesting a direct
      relationship with CD in 19.3%. Our study revealed a variety of neurologic and
      neuropsychologic events, such as seizure disorder, cerebrovascular accident,
      headache, peripheral neuropathy, myopathy, and major depression. We believe that
      an autoimmune phenomenon affecting the small vessels of the central and
      peripheral nerves may cause the most common neurologic complications of CD.

PMID- 9191735
TI  - Tobacco smoking: a survey in a community with excess lung cancer.
AB  - Duval County, Florida (Jacksonville) has had one of the highest lung cancer
      mortality rates among large US cities in recent decades. This survey was
      conducted to determine whether this might be due in part to higher prevalence or
      amount of smoking. Telephone interviews using a random digit dialing technique
      were conducted with 3,105 residents. Questions on cigarette smoking were taken
      from national surveys, and Jacksonville rates were compared with US rates. The
      percentage of persons in Jacksonville who had ever smoked was similar to the
      national percentage. Among whites, however, the prevalence of current smokers was
      slightly higher, and of heavy smokers was significantly higher, than national
      rates for whites; while among blacks, smoking prevalence and amount were below
      national rates for blacks. Up to one third of the excess lung cancer mortality
      rates in male and female whites in Jacksonville might be accounted for by the
      heavier amounts smoked by residents.

PMID- 9191737
TI  - Characteristics of patients with rapidly growing cervical cancer.
AB  - Between April 1983 and December 1990, 387 newly diagnosed cervical cancer cases
      were managed at our institution. We retrospectively reviewed 59 of those cases,
      which were identified as having developed within 3 years of the patients' last
      normal Pap smear. Squamous cell carcinoma was found in 45 patients, and 33 had
      poorly differentiated lesions. Six cases had typical histology. However, 27 cases
      (82%) had distinctive histologic features that have not been previously described
      in rapidly progressive cervical cancer. Thirty-seven patients had surgical
      treatment; 7 (19%) died of disease. Twenty-two patients had radiation; 10 (45%)
      died of disease. Patients who have invasive cervical cancer after a recent normal
      Pap smear may have unusual histologic types, and some with early-stage disease
      may have better outcome if treated with radical surgery.

PMID- 9191738
TI  - Use of emergency departments by the elderly in rural areas.
AB  - Sparse information is available concerning use of emergency departments (EDs) by
      the elderly in rural areas. We reviewed records of all patients seeking care at
      EDs of three rural hospitals during 7 days in October 1991. We found that elderly
      people did not use EDs in proportion to their numbers in the community (15.2%
      versus 19.3%). Compared with younger ED patients, more elderly patients required
      an ambulance (40.8% versus 10.7%), more needed hospitalization (38.4% versus
      11.9%), and their ED stays were longer (140 minutes versus 89 minutes).
      Falls/injuries (18.7%) and cardiac illness (18.1%) were the most frequent reasons
      for ED visits by the elderly, and relatively few (2.8%) had confusion. More
      elderly patients arrived during daytime hours than during the night, and more on
      weekends than weekdays. Also, we found no difference between patients in the 65-
      to 74-year-old age group and those aged 75 years and older.

PMID- 9191739
TI  - In vitro activities of oral antimicrobial agents against penicillin-resistant
      Streptococcus pneumoniae: implications for outpatient treatment.
AB  - We tested 83 penicillin-intermediate (Peni) and 50 penicillin-resistant (Penr)
      isolates of Streptococcus pneumoniae against eight oral antimicrobials.
      Clarithromycin's MICs (minimal inhibitory concentration) were generally the same
      or one to two dilutions less than those of azithromycin. Seventy-two percent of
      Peni isolates were susceptible to clarithromycin and azithromycin, in contrast to
      42% and 40%, respectively, of Penr isolates. Cefuroxime activity exceeded that of
      cefprozil, which exceeded that of cefaclor, in Peni isolates. For all three
      cephalosporins, MICs of 90% of isolates tested were > or = 3 dilutions higher for
      Penr isolates than for Peni isolates. Percentages of Peni isolates susceptible to
      clindamycin and tetracycline were 92% and 83%, respectively, and 78% and 82% for
      Penr. Only 49% of Peni isolates and 4% of Penr isolates were susceptible to
      trimethoprim-sulfamethoxazole. Azithromycin, clarithromycin, cefuroxime,
      cefprozil, clindamycin, and tetracycline may be useful in treating infections
      caused by Peni S pneumoniae, but Penr isolates are frequently resistant to both
      old and newer agents.

PMID- 9191740
TI  - Ventilator management of infants before extracorporeal membrane oxygenation.
AB  - The aim of this project was to review the course of infants referred for
      consideration of extracorporeal membrane oxygenation (ECMO) to identify maximal
      ventilator settings that, when exceeded, did not provide clinical benefit to the
      patient. These settings might then be used in defining failure of conventional
      mechanical ventilation. We reviewed referral records and hospital charts of all
      infants treated for severe respiratory failure due to meconium aspiration
      syndrome during the 52.5 month period from March 15, 1985, to August 1, 1989. At
      an inspiratory pressure > 35 cm H2O, 75% (43/57) of patients eventually required
      ECMO, and 28% (4/14) of the infants who did not receive ECMO died. When the
      inspiratory pressure was > or = 40 cm H2O, 39/49 patients required ECMO, and 30%
      (3/10) of those not treated with ECMO died. Once the inspiratory pressure was >
      45 cm H2O, 91% (29/32) of patients required ECMO, and only one third of those not
      treated with ECMO survived. Although the limitations for conventional therapy
      suggested in this paper may be helpful to clinicians, each center needs to
      establish guidelines for maximal conventional ventilator support. If these
      guidelines are clearly defined, alternative methods of therapy can be used once
      these criteria are achieved.

PMID- 9191741
TI  - Isolated splenic metastases from colon cancer.
AB  - Metastatic tumors of the spleen are rare and usually occur in the presence of
      disseminated visceral metastases. The liver is the most common site of metastatic
      spread from colon cancer. We report a case of isolated intrasplenic metastasis
      from sigmoid colon cancer and review the possible reasons for the rarity of
      splenic metastasis. This represents the fifth reported case of isolated splenic
      metastasis from colon cancer. Splenectomy may be justified in presence of
      isolated metastatic disease, since it is an operation with a low complication
      rate and may provide potential long-term survival in colon cancer.

PMID- 9191742
TI  - Ferrous sulfate-induced increase in requirement for thyroxine in a patient with
      primary hypothyroidism.
AB  - Recent studies have shown that under experimental conditions ferrous sulfate may
      reduce the gastrointestinal absorption of orally administered levothyroxine
      sodium in patients with primary hypothyroidism. We describe a patient who became
      hypothyroid while taking ferrous sulfate. The hypothyroid status was corrected by
      increasing the dose of levothyroxine. Subsequently, when ferrous sulfate was
      discontinued, the patient became hyperthyroid while taking the higher dose of
      thyroid hormone preparation. Since both hypothyroidism and iron deficiency anemia
      may coexist, additional thyroid function testing is recommended in patients
      treated concurrently with ferrous sulfate and L-thyroxine.

PMID- 9191743
TI  - Lemierre's syndrome.
AB  - Lemierre's syndrome is an acute medical condition characterized by anaerobic
      oropharyngeal infection leading to septic thrombophlebitis of the internal
      jugular vein. The illness is often complicated by septic pulmonary emboli and
      distant metastatic infections. Treatment consists of surgical drainage of
      purulent collections and long-term intravenous antibiotic therapy. Although
      Lemierre's syndrome is rare, it is potentially fatal and remains an important
      entity for clinicians to recognize and treat appropriately.

PMID- 9191744
TI  - Delayed onset of pseudomembranous colitis after rifampin therapy.
AB  - Rifampin therapy is an infrequently reported cause of pseudomembranous colitis. A
      low index of suspicion may account for this lack of recognition. Awareness of
      this potentially hazardous complication of rifampin therapy is encouraged,
      especially since increasing numbers of patients infected with the human
      immunodeficiency virus, who may have diarrhea from other etiologies, require
      rifampin therapy.

PMID- 9191745
TI  - Campho-Phenique ingestion: an intentional overdose.
AB  - We report a suicide attempt with the camphorated phenol preparation Campho
      Phenique. The total dose ingested was 68 mg/kg of camphor and 28.9 mg/kg of
      phenol. The patient had grand mal seizures minutes after ingestion. Supportive
      medical care and intubation resulted in full recovery within 12 hours. Although
      Campho-Phenique has been discussed extensively in the pediatric literature and
      its accidental ingestion by adults has occasionally been reported, intentional
      ingestion of the preparation has not been reported. We discuss our unusual case
      and review the literature.

PMID- 9191746
TI  - Pneumococcal sacroiliitis.
AB  - We report an unusual case of Streptococcus pneumoniae sacroiliitis in a
      previously healthy 31-year-old woman. Six cases of pneumococcal sacroiliitis have
      been reported; the only two cases in adults occurred in young women in the
      preantibiotic era. Our patient had fever and a depressed level of consciousness,
      with subsequent right buttock and thigh pain. Blood cultures revealed S
      pneumoniae, and a bone scan showed increased tracer activity in the right
      sacroiliac joint. Although the cerebrospinal fluid white blood cell count was
      only 3/microL, culture of cerebrospinal fluid grew S pneumoniae. Our patient was
      successfully treated with a 6-week course of intravenous antibiotics (penicillin
      G after an initial week of ceftriaxone), followed by 2 weeks of oral penicillin
      therapy.

PMID- 9191747
TI  - Late recurrence of seminoma.
AB  - Patients with testicular cancer usually are cured if they survive disease-free
      for 2 years after therapy. We report a case of documented seminoma that recurred
      at both 21 years and 32 years after the patient's orchiectomy. We discuss late
      recurrences in germ cell cancer, possible mechanisms of recurrence, and the need
      for life-long surveillance.

PMID- 9191748
TI  - Systemic ehrlichiosis presenting as progressive hepatosplenomegaly.
AB  - A 42-year-old white man had headache, fever, chills, abdominal pain, nausea and
      vomiting, night sweats, and dark urine for 3 days before admission; he had
      history of a tick bite 6 weeks earlier. Progressive systemic deterioration,
      heralded by progressive hepatosplenomegaly and pancytopenia, occurred despite
      doxycycline therapy. Subsequent recovery was preceded by progressive resolution
      of hepatosplenomegaly. Progressive hepatosplenomegaly has not been previously
      reported in association with systemic monocytic ehrlichiosis.

PMID- 9191749
TI  - Primary breast cancer in aberrant breast tissue in the axilla.
AB  - Primary breast cancer in aberrant axillary breast tissue is rare. Breast cancer
      in the axilla is most often due to lymph node metastases from an ipsilateral
      breast tumor or from an occult primary lesion. We describe two patients with
      primary breast cancer in aberrant breast tissue in the axilla, and review the
      literature to define guidelines for diagnosis and treatment.

PMID- 9191750
TI  - Tick-borne diseases in the United States.

PMID- 9191751
TI  - Endarterectomy for asymptomatic internal carotid artery stenosis.

PMID- 9191752
TI  - Apraxia of lid opening: a review.

PMID- 9191753
TI  - Unusual causes of headache.

PMID- 9191754
TI  - Use of gold weights to correct lagophthalmos in neuromuscular disease.
AB  - Upper eyelid gold-weight implants are widely used in the correction of
      lagophthalmos in many neuromuscular conditions, most commonly facial palsy. The
      paralytic lagophthalmos that occurs in facioscapulohumeral muscular dystrophy
      (FSHD) is common and can cause severe ocular complications. It is not usually
      considered for surgical correction. Upper lid loading with 24K gold implants and
      reconstructive lower lid surgery in a 64-year-old woman with FSHD corrected
      eyelid deformity and exposure keratitis. Surgical treatment also markedly
      improved facial appearance. This treatment may merit wider use in FSHD.

PMID- 9191755
TI  - Silicone breast implants and neurologic disorders. Report of the Practice
      Committee of the American Academy of Neurology.

PMID- 9191756
TI  - Clinical dementia rating training and reliability in multicenter studies: the
      Alzheimer's Disease Cooperative Study experience.
AB  - Global ratings of dementia severity are used increasingly in clinical trials of
      antidementia compounds. Such ratings are clinically relevant, but their
      reliability in multicenter settings has not been determined. To evaluate the
      reliability of one global scale, the Clinical Dementia Rating (CDR), 82
      investigators of the multicenter Alzheimer's Disease Cooperative Study
      participated in a training and reliability protocol using videotaped assessments
      of subjects in various stages of Alzheimer's disease. Following training, overall
      agreement of the investigators with "gold standard" CDR scores was 83%. These
      results indicate that the training protocol is useful for establishing good
      levels of agreement in staging dementia severity and that the CDR can be
      standardized as a clinical global scale for multicenter studies of Alzheimer's
      disease.

PMID- 9191757
TI  - The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline
      cognitive performance in multicenter Alzheimer's disease trials.
AB  - The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is
      used as an efficacy measure in clinical drug trials of Alzheimer's disease (AD).
      We used data from 1,648 AD participants in two identical 26-week multicenter drug
      trials to examine the distribution of baseline ADAS-Cog scores in relation to
      selected demographic and clinical variables, Mini-Mental State Exam (MMSE),
      Global Deterioration Scale (GDS), and Geriatric Evaluation by Relative's Rating
      Instrument (GERRI) scores. At baseline, the mean (+/-SD) MMSE score was 18 +/- 4,
      the ADAS-Cog score was 28 +/- 11, and most subjects were in GDS stage 4 or 5. The
      ADAS-Cog score was statistically significantly correlated with MMSE (R = -0.76, p
      < 0.0001) and GERRI (R = 0.40, p < 0.0001) total scores. Correlations among the
      ADAS-Cog items ranged from 0.19 to 0.59 and all were statistically significant (p
      < 0.0001). In a multiple regression model, younger age, male gender, older age at
      onset of dementia, use of concurrent estrogen, and use of concurrent anti
      inflammatory agents were statistically significantly associated with superior
      cognitive performance. We also present data on the distribution of ADAS-Cog
      scores in relation to subjects' age, level of education, MMSE score, and GDS
      stage. Because age, MMSE score, and GDS stage (and not the ADAS-Cog) are commonly
      used to select subjects for AD clinical trials, our data should improve the
      ability of sponsors to predict ADAS-Cog scores of the subjects in their trials on
      the basis of the inclusion criteria used. Our data also suggest that age, gender,
      age at onset of dementia, level of education, and use of estrogen (in women) or
      anti-inflammatory drugs are related to cognitive abilities in AD. Further studies
      are needed to assess how and when cognitive differences related to these
      variables arise.

PMID- 9191758
TI  - A prospective study of estrogen replacement therapy and the risk of developing
      Alzheimer's disease: the Baltimore Longitudinal Study of Aging.
AB  - Previous reports have suggested that estrogen replacement therapy (ERT) in women
      may exert a protective effect on their risk of developing Alzheimer's disease
      (AD). We investigated this relationship in the Baltimore Longitudinal Study of
      Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by
      the National Institute on Aging. The sample consisted of 472 post- or
      perimenopausal women followed for up to 16 years in the BLSA. We documented ERT
      prospectively at each BLSA visit, and we categorized women who had used oral or
      transdermal estrogens at anytime as ERT users. We used Cox proportional hazards
      models with time-dependent covariates to estimate the relative risk of developing
      AD after ERT as compared with women who had not used estrogen replacement.
      Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34
      incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine
      estrogen users. After adjusting for education, the relative risk for AD in ERT
      users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a
      reduced risk of AD for women who had reported the use of estrogen. Our data did
      not show an effect for duration of ERT usage. Our finding offers additional
      support for a protective influence of estrogen in AD. Randomized clinical trials
      are necessary to confirm this association, which could have significant public
      health impact.

PMID- 9191759
TI  - EEG spectral abnormalities and psychosis as predictors of cognitive and
      functional decline in probable Alzheimer's disease.
AB  - We examined whether either psychotic features (e.g., delusions and
      hallucinations) or EEG abnormalities are associated with more rapid progression
      of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG
      abnormalities than those without psychosis, and both abnormal EEG and psychosis
      have been noted to be predictors of functional and cognitive decline in AD.
      Ninety-five probable AD patients participating in a longitudinal study of
      dementia had an EEG and a semistructured psychiatric interview at baseline. Using
      EEG spectral analysis, we classified records as normal/abnormal based on the
      parasagittal mean frequency. Patients with abnormal EEGs were more functionally
      (e.g., Blessed Rating Scale for activities of daily living) and cognitively
      (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients
      with psychosis were only more functionally impaired than patients without
      psychosis. A two-factor analysis showed no interaction between abnormal EEG and
      psychosis. In addition, using a Cox proportional hazard model adjusted for age
      and education, the presence of an abnormal EEG or psychotic symptom at study
      entry was associated with higher risk of reaching severe cognitive and functional
      impairment during follow-up. Neither abnormal EEG nor the presence of psychosis
      predicted death. These results indicate that both abnormal EEG and psychosis are
      independent predictors of disease progression but not of physical survival.

PMID- 9191761
TI  - Spatial dysgraphia and cerebellar lesion: a case report.
AB  - Spatial dysgraphia is a writing disorder that occurs in patients with right
      hemisphere lesion. We report a patient with cerebellar atrophy and spatial
      dysgraphia. To explain this finding, we hypothesize a discoordination between
      planning of the movement and performance due to a lack of the cerebellar
      modulation between supratentorial (premotor cortex) and peripheral
      (proprioceptive) afference during the ongoing handwriting movement.

PMID- 9191760
TI  - Apolipoprotein E gene and sporadic frontal lobe dementia.
AB  - The apolipoprotein E gene has been associated with various types of dementia. We
      studied the connection between the APOE gene and the risk and onset of disease in
      34 patients with clinically diagnosed frontal lobe dementia (FLD) derived from a
      population-based study in the Netherlands. A significant increased risk of FLD
      (odds ratio, 4.9; 95% CI, 1.1-20.1) was found for the apoE4E4 genotype when
      adjusting for age, sex, and family history of dementia other than FLD. The age at
      onset of the disease decreased as the number of APOE*4 alleles increased. Our
      population-based study suggests that persons who are homozygous for the APOE*4
      allele are at increased risk for developing FLD.

PMID- 9191762
TI  - Disruption of short-duration timing associated with damage to the suprachiasmatic
      region of the hypothalamus.
AB  - The neural bases of circadian rhythmicity have been demonstrated in a variety of
      animal species, including primates. Yet, the brain mechanisms underlying time
      experience and the timing of behaviors of shorter duration are still not well
      understood. In the present study, we demonstrate disruption of short-duration
      timing capacity in AH, a patient with damage to the suprachiasmatic (SCN) region
      of the hypothalamus. AH exhibited extreme inconsistency in her rate of tapping
      production on a motor continuation paradigm. Her inter-response intervals (IRIs)
      were extremely large compared with normal control subjects and were similar to
      those previously reported in patients with cerebellar dysfunction. Increased
      variability of both central timing and motor implementation processes was evident
      compared with both age-matched and elderly normal control subjects. Severe
      impairment of time perception was also evident on duration discrimination,
      whereas auditory loudness discrimination was intact. These findings suggest that
      a hierarchic relationship between long-duration (circadian) and short-duration
      timing exists, and that in addition to the cerebellum, intact hypothalamic
      functioning is necessary for short-duration timing.

PMID- 9191763
TI  - Analgesic rebound as a cause of hemicrania continua.
AB  - Hemicrania continua is a rare unilateral headache of unknown etiology that
      characteristically responds to indomethacin. Most previous case reports fail to
      mention analgesic use by these patients or the results of analgesic avoidance.
      This is a case report of a 42-year-old woman with persistent unilateral headaches
      that ceased 3 weeks after administration of analgesics was stopped. Thus,
      hemicrania continua can be caused by analgesic rebound.

PMID- 9191764
TI  - A study of the effects of sumatriptan on myocardial perfusion in healthy female
      migraineurs using 13NH3 positron emission tomography.
AB  - Sumatriptan, a 5-HT1D receptor agonist, is believed to alleviate migraine attacks
      by extracerebral vasoconstriction. Chest pain associated with myocardial ischemia
      may occur after sumatriptan administration. We investigated the effect of a
      single 6-mg subcutaneous dose of sumatriptan on myocardial perfusion (MP) as
      measured by 13NH3 positron emission tomography (PET) in a randomized, double
      blind, placebo-controlled, crossover trial at the Clinical PET Centre, Guy's and
      St. Thomas' Hospitals, London. Nineteen volunteer female migraineurs, age range
      33 to 62 years, at low risk for ischemic heart disease were included. All bad
      undergone previous treatment with oral or intravenous sumatriptan. Patients were
      recruited by advertisement and referral from local neurology specialists. Each
      volunteer underwent two scanning sessions. On each occasion, a baseline dynamic
      13NH3 PET scan was acquired followed by a 13NH3 PET scan 10 minutes after
      subcutaneous injection of placebo or 6 mg of sumatriptan. Regional MP was
      measured in five myocardial regions using the Patlak system of image analysis.
      The mean % change from baseline (+/-SD) in global MP after placebo was +9.5% +/-
      18.0 and after sumatriptan was +6.6% +/- 18.8 (repeated measures ANOVA for
      treatment effect p = 0.56). There were no significant differences in MP changes
      from baseline observed in any of the five myocardial regions (treatment p = 0.32
      to 0.84). These data suggest that in healthy female migraineurs, a single 6-mg
      subcutaneous dose of sumatriptan does not cause a significant change in regional
      or global myocardial perfusion.

PMID- 9191765
TI  - HLA DR15 (DR2) and DQB1*0602 typing studies in 188 narcoleptic patients with
      cataplexy.
AB  - Narcolepsy is considered a homogeneous clinical entity when excessive daytime
      sleepiness and cataplexy are present. Cataplexy is a polymorphic symptom that can
      be very mild and is thus subjectively defined. The Multiple Sleep Latency Test
      (MSLT) is widely used as a diagnostic test for narcolepsy. A short mean sleep
      latency and multiple sleep onset REM periods (SOREMPs) are typically observed in
      narcoleptic patients. The discovery of a tight association of narcolepsy with HLA
      class II antigens offers a unique opportunity to explore the respective value of
      the MSLT or of the presence of clear-cut cataplexy in defining an etiologically
      homogeneous group of narcoleptic patients. In this study, we carried out HLA
      typing for DR15(DR2) and DQB1*0602 in 188 narcoleptic patients with cataplexy in
      three ethnic groups (24 Asians, 61 Blacks, and 103 Caucasians). These results
      confirm the importance of DQB1*0602 typing rather than DR15 (DR2) typing in Black
      narcoleptic patients and demonstrate that the presence of clear-cut cataplexy is
      a better predictor for DQB1*0602 positivity than the presence of abnormal MSLT
      results.

PMID- 9191766
TI  - Longitudinal study of soluble adhesion molecules in multiple sclerosis:
      correlation with gadolinium enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To assess whether serial serum levels of soluble forms of
      intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1
      (sVCAM-1) are useful as surrogate markers of disease activity in multiple
      sclerosis (MS). BACKGROUND: Increased levels of sICAM-1 and sVCAM-1 have been
      described in cross-sectional, but not longitudinal, studies of patients with MS.
      Although they appear to correlate with clinical and MRI markers of disease
      activity, their role as potential surrogate markers remains undefined. METHODS:
      Serial serum levels of sICAM-1 and sVCAM-1 were measured in patients with MS
      undergoing monthly gadolinium-enhanced MRI studies of the brain (462 gadolinium
      enhanced MRI in 57 patients) and in 12 normal control subjects. Ten patients had
      primary progressive (PP), 22 relapsing remitting (RR), and 25 secondary
      progressive (SP) disease. RESULTS: Levels of sICAM-1 and sVCAM-1 were increased
      intermittently in patients with all subtypes of MS. Median levels of sICAM-1 were
      elevated in patients with MS compared with normal controls (normal controls
      median [interquartile range] = 176[119-209] compared with PP = 502[194-1768], RR
      = 419[158-481], and SP = 352[196-469] ng/mL; p = 0.04). After excluding patients
      with PP MS, patients with high sICAM-1 levels had a greater number of gadolinium
      enhancing lesions per study (1.9[0.9-4.3]) than patients with normal levels
      (0.4[0-2.7], p = 0.03), and patients with MRI studies with no gadolinium
      enhancing lesions had lower associated sICAM-1 levels (200 ng/mL[85-561]) than
      patients with only persistent (349 ng/mL[82-615]) or new enhancing lesions (497
      ng/mL[108-667], p = 0.03). Patients with RR or SP disease that progressed
      clinically during the study had a greater number of gadolinium-enhancing lesions
      per MRI study (3.5[0.4-5.5]) than did patients in whom disease did not progress
      (1.2 [0.3-2.7], p = 0.03). The patients with progressive disease tended to have
      higher sICAM-1 levels (469 ng/mL [196-1019]) than patients in whom disease did
      not progress (353 ng/mL [171-469], p = 0.07). Although MS patients tended to have
      higher sVCAM-1 levels than did normal controls, this finding was not significant.
      No correlation could be found between levels of sVCAM-1 and gadolinium
      enhancement on MRI. CONCLUSIONS: Patients with MS have elevated levels of sICAM
      1, which correlate with gadolinium enhancement on MRI and possibly short-term
      disease progression. Soluble ICAM-1, and not sVCAM-1, may therefore be suitable
      as a long-term surrogate marker of disease activity in MS.

PMID- 9191767
TI  - Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple
      sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission
      tomography study.
AB  - To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose
      metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose.
      Applying the Fatigue Severity Scale (FSS), we first compared MS patients with
      severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS
      NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric
      Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the
      whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In
      addition, we determined global CMRGlu by region-of-interest analysis. Sixteen
      healthy subjects served as control subjects (CON). Global CMRGlu was
      significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9
      mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related
      to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed
      predominant CMRGlu reductions bilaterally in a prefrontal area involving the
      lateral and medial prefrontal cortex and adjacent white matter, in the premotor
      cortex, putamen, and in the right supplementary motor area of MS-FAT. In
      addition, there were CMRGlu reductions in the white matter extending from the
      rostral putamen toward the lateral head of the caudate nucleus. FSS values were
      inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the
      cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in
      MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS
      values. Our data suggest that fatigue in MS is associated with frontal cortex and
      basal ganglia dysfunction that could result from demyelination of the frontal
      white matter.

PMID- 9191768
TI  - Secondary dystonia and the DYTI gene.
AB  - Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a
      single founder mutation in the DYT1 gene on chromosome 9q34, as determined by
      very strong linkage disequilibrium with a haplotype of 9q34 alleles at
      surrounding marker loci. The role of this mutation in individuals with secondary
      causes for dystonia has never been tested, although environmental insults, such
      as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate
      dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in
      40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms,
      including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of
      the 25 patients with early onset, 9 were considered phenocopies of DYT1 having
      normal examinations except for dystonia, normal radiographic and other laboratory
      studies, and onset in a limb or the neck. Only one individual whose dystonia
      developed in the setting of a measles infection carried the associated haplotype.
      Our findings indicate that clinical diagnostic criteria that include historical
      information to detect tardive dystonia and perinatal asphyxia discriminate
      primary dystonia due to the DYT1 founder mutation. We found no evidence that the
      DYT1 founder mutation contributes to secondary dystonia.

PMID- 9191769
TI  - [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive
      Parkinson's disease: implications for the symptomatic threshold.
AB  - To estimate the threshold of nigrostriatal dysfunction required for symptomatic
      Parkinson's disease (PD), we employed [11C]RTI-32 and PET to study the dopamine
      transporter in striatal subdivisions of 11 L-dopa-naive patients with very early
      parkinsonism. As compared with the controls (N = 10), the PD group had on the
      side contralateral to the maximal clinical symptoms, significantly reduced
      binding in the posterior putamen (-56%) and anterior putamen (-28%), with the
      reduction in caudate (-12%) not significantly different. To the extent that
      dopamine transporter binding accurately reflects the number of nigrostriatal
      dopamine nerve terminals, these findings suggest that the clinical threshold for
      PD in the middle-age human is approximately 50% loss of dopaminergic innervation
      to the posterior putamen. Our data also suggest that damage to the putamen
      component of the striatum is sufficient for the clinical expression of PD.

PMID- 9191770
TI  - Environmental risk factors and Parkinson's disease: a case-control study in
      Taiwan.
AB  - To explore environmental risk factors for Parkinson's disease (PD) in Taiwan, we
      investigated 120 patients with PD and 240 hospital control subjects matched with
      patients on age (+/-2 years) and sex. Based on a structured open-ended
      questionnaire, we carried out standardized interviews to obtain history of
      exposure to environmental factors, including place of residence, source of
      drinking water, and environmental and occupational exposures to various
      agricultural chemicals. In the univariate analysis, the history of living in a
      rural environment, farming, use of herbicides/pesticides, and use of paraquat
      were associated with an increased PD risk in a dose-response relationship. After
      adjustment for multiple risk factors through conditional logistic regression, the
      biological gradient between PD and previous uses of herbicides/pesticides and
      paraquat remained significant. The PD risk was greater among subjects who had
      used paraquat and other herbicides/pesticides than those who had used
      herbicides/pesticides other than paraquat. There were no significant differences
      in occupational exposures to chemicals, heavy metals, and minerals between PD
      patients and matched control subjects. The duration of drinking well water and
      alcohol consumption was not significantly associated with PD. There was an
      inverse relationship between cigarette smoking and PD. Environmental factors,
      especially exposures to paraquat and herbicides/pesticides, may play important
      roles in the development of PD in Taiwan.

PMID- 9191772
TI  - Embolic brain infarction in nonrheumatic atrial fibrillation: a clinicopathologic
      study in the elderly.
AB  - Although CT studies have addressed symptomatic and asymptomatic cerebral
      infarctions in nonrheumatic atrial fibrillation (NRAF), pathologic verification
      of the results is lacking. The purpose of this study was to assess the frequency,
      location, and extent of symptomatic and asymptomatic brain infarction in autopsy
      specimens from elderly patients with NRAF. We examined autopsy specimens from 136
      consecutive NRAF patients 70 years of age or older who received no anticoagulant
      therapy during their lifetime and compared them with 231 age-matched control
      subjects with similar health histories except for the absence of NRAF.
      Symptomatic cerebral infarctions were present in 82 (60.3%) NRAF patients and in
      55 (23.8%) control subjects (p < 0.0001). Of symptomatic cerebral infarctions,
      cardioembolic infarction was present in 53 (64.6%) NRAF patients and in two
      (3.6%) of the control subjects (p < 0.0001), atherothrombotic infarction in 13
      (15.9%) NRAF patients versus 36 (65.5%) control subjects (p < 0.0001), and
      lacunar infarction in four (4.9%) NRAF patients versus 12 (21.8%) control
      subjects (p < 0.01). Stroke-related death occurred in 34 (25.0%) NRAF patients
      and in 18 (7.8%) control subjects (p < 0.0002). Symptomatic cerebral infarction
      was generally accompanied by asymptomatic infarctions in both NRAF patients and
      control subjects. Asymptomatic cortical infarctions were more common in NRAF
      patients, but asymptomatic infarctions in the white matter or deep structures
      were more common in control subjects. In this autopsy series of individuals over
      70 years of age, symptomatic brain infarction was 2.5 times more common in NRAF
      patients than in NRAF-free control subjects; two-thirds of the infarctions in the
      NRAF cases were judged to be cardioembolic in origin. Most asymptomatic cerebral
      infarctions in the NRAF patients were located in the cortices.

PMID- 9191771
TI  - Evaluation of four candidate genes encoding proteins of the dopamine pathway in
      familial and sporadic Parkinson's disease: evidence for association of a DRD2
      allele.
AB  - We assessed the role of four candidate genes encoding proteins involved in
      dopaminergic transmission, the dopamine transporter (DAT), the dopamine receptor
      D2 (DRD2), and the main catabolic enzymes of dopamine, monoamine oxidase A (MAOA)
      and B (MAOB), through allelic association studies in a population of familial and
      sporadic Parkinson's disease (PD). Using intronic polymorphisms of the four
      candidate genes, we studied the allelic distributions of the polymorphic markers
      in 18 affected members, one patient was chosen randomly from each PD family; 60
      sporadic PD and 60 healthy unrelated control subjects were matched for sex and
      for country of origin. All subjects were white. To complete the study of the
      DRD2, we subsequently tested 40 additional sporadic PD and 40 control patients,
      who were recruited using a similar procedure. For DAT, MAOA, MAOB polymorphisms,
      similar allelic frequencies were present in familial, sporadic PD and control
      patients. In contrast, at the DRD2 locus, the overall allelic distribution was
      significantly different in the sporadic PD (p < 0.01) and in the familial PD
      groups (p < 0.05), each was compared with the controls. The odd ratios were
      significant (p < 0.01) in sporadic PD and in familial PD for allele 3 with
      respective values of 1.84 (95% CI, 1.23-2.74) and 2.83 (95% CI, 1.32-6.08).
      Individuals who were homozygous for allele 3 were 2.3 times more frequent in the
      sporadic PD than in controls. Results suggest that DRD2, but not DAT, MAOA and
      MAOB, might be a genetic determinant of PD in the population tested.

PMID- 9191773
TI  - Clinical characteristics and management of acute stroke in patients with atrial
      fibrillation admitted to US university hospitals.
AB  - The optimal evaluation and management of patients with atrial fibrillation who
      suffer an acute ischemic stroke remains controversial. METHODS: Medical records
      of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S.
      university hospitals were reviewed. Data collected included the use of
      antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke
      risk factors, and contraindications to anticoagulation. RESULTS: Mean age was
      75.4 years. Cardiovascular risk factors associated with increased stroke risk
      were present in 87%; 35% had at least one contraindication to anticoagulation.
      Half of the patients with stroke risk factors and no contraindications to
      anticoagulation were not receiving any antithrombotic therapy at the time of
      admission. Of the 22 patients who were treated with warfarin, and had INR values
      on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and
      3.0. Transthoracic echocardiography was performed in 107 patients (63%);
      intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed
      hemorrhagic transformation in nine. Heparin was used in 93 patients (54%),
      usually within 48 hours of stroke onset. Patients who received delayed heparin
      typically did not have repeat brain imaging prior to starting heparin. One
      patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were
      discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7%
      with other antithrombotic therapies, and 18% with no antithrombotic therapy.
      CONCLUSION: Antithrombotic therapy was underutilized and inadequately monitored
      in atrial fibrillation patients prior to stroke onset. After hospital admission,
      a wide range of diagnostic and management strategies, which often did not follow
      current recommendations, were employed.

PMID- 9191774
TI  - Fibromuscular dysplasia with dissection of basilar artery presenting as "locked
      in-syndrome".
AB  - We report on a young man with fibromuscular dysplasia involving the basilar
      artery detected at autopsy. He presented with sudden onset of stroke, and the
      lesion was complicated by thrombosis and dissection of the vessel wall. The
      organizing thrombotic lesion of the basilar artery was responsible for the
      ventral pontine infarct that resulted in "locked-in syndrome."

PMID- 9191775
TI  - Barbiturate coma in severe hemispheric stroke: useful or obsolete?
AB  - Barbiturates are administered in a variety of clinical conditions to control
      elevated intracranial pressure (ICP). However, their routine use to treat
      elevated ICP has been questioned because it may cause severe side effects. We
      therefore investigated the effect of high-dose barbiturate therapy on ICP and
      outcome in patients with severe brain edema after severe middle cerebral artery
      (MCA) or hemispheric infarction. Barbiturate coma was induced with thiopental
      infusion in 60 patients with critically increased ICP due to large hemispheric or
      MCA territory infarction, defined by CT. ICP was monitored in all patients during
      barbiturate therapy. Barbiturate coma was induced after a standardized treatment
      protocol for increased ICP after failure of osmotherapy and mild
      hyperventilation. During barbiturate administration, cerebral perfusion pressure
      (CPP) and mean arterial pressure were recorded. Clinical outcome of these
      patients and the individual effect on ICP were analyzed. Only five of 60 patients
      who were treated with barbiturate coma survived (8%). All other patients died
      after transtentorial herniation with subsequent brain death. Barbiturate infusion
      was followed by a drop in ICP in 50 patients and showed no effect on ICP values
      in 10 patients. CPP decreased with a mean of 9 mm Hg (range, 5 to 20 mm Hg).
      Although barbiturates were initially effective, only in some patients was ICP
      control sustained. Severe side effects of barbiturate therapy, besides arterial
      hypotension, were seen in 15 patients (25%). Barbiturate coma in the therapy of
      increased ICP after severe ischemic hemispheric stroke can lower critically
      elevated ICP levels. However, it seems to have no positive effect on neurologic
      outcome.

PMID- 9191776
TI  - Local thrombolytic therapy in deep cerebral venous thrombosis.
AB  - Thrombosis of the deep cerebral venous system is a rare entity with a very poor
      prognosis. We report two patients with thrombosis of the internal cerebral veins
      and vein of Galen who responded to local urokinase. We review all 49 cases of
      deep cerebral venous thrombosis in the English literature. The mortality rate for
      patients treated with either IV heparin or local thrombolytics was 13% compared
      with 48% in untreated patients (p = 0.037). Based on this retrospective review of
      the literature and our two cases, we support the use of heparin or local
      thrombolytics in individual cases of deep cerebral venous thrombosis.

PMID- 9191777
TI  - A case of acute monocytic ehrlichiosis with prominent neurologic signs.
AB  - Human monocytic ehrlichiosis is a recently described tick-borne infection with
      the rickettsial organism Ehrlichia chaffeensis. We describe a patient with
      documented E chaffeensis infection and multiple organ system involvement.
      Prominent neurologic symptoms and signs included severe headache, meningismus,
      and altered mental status. Additional neurologic findings included unilateral arm
      weakness and a Bell's palsy. Biopsy of brain and meninges demonstrated an
      infiltrate of atypical lymphoid cells in the leptomeninges with involvement of
      blood vessel walls and extension into the Virchow-Robin spaces. Bone marrow
      biopsy revealed fibrin-ringed granulomas. The patient also developed a
      nonspecific increase in immunoglobulin production. Host immune response may play
      a critical role in the pathophysiology of ehrlichiosis.

PMID- 9191778
TI  - Leber's hereditary optic neuropathy: biochemical effect of 11778/ND4 and 3460/ND1
      mutations and correlation with the mitochondrial genotype.
AB  - To clarify the bioenergetic relevance of mtDNA mutations in Leber's hereditary
      optic neuropathy (LHON), we investigated affected individuals and healthy
      carriers from six Italian LHON families harboring the 11778/ND4 and the 3460/ND1
      mtDNA mutations. The enzymatic activities of mitochondrial complex I and its
      sensitivity to the potent inhibitors rotenone and rolliniastatin-2 were studied
      in mitochondrial particles from platelets, in correlation with mtDNA analysis of
      platelets and leukocytes. In platelets homoplasmic for mutant mtDNA, both
      11778/ND4 and 3460/ND1 mutations induced resistance to rotenone and the 3460/ND1
      mutation also provoked a marked decrease in the specific activity of complex I.
      Individuals heteroplasmic in platelets for either mutation showed normal
      biochemical features, indicating functional complementation of wild-type mtDNA.
      There was no correlation between the clinical status and mtDNA homo/heteroplasmy
      in platelets, but the biochemical features correlated with the mitochondrial
      genotype of platelets. In some cases, the degree of mtDNA heteroplasmy differed
      in platelets and leukocytes from the same individual with a prevalence of wild
      type mtDNA in the platelets. These results imply that biochemical studies on
      mitochondrial diseases should always be integrated with mtDNA analysis of the
      same tissue investigated and also suggest that the mtDNA analysis on the
      leukocyte fraction, as usually performed in LHON, does not necessarily reflect
      the mutant genotype level of other tissues. The differential tissue heteroplasmy
      may be more relevant than previously thought in determining disease penetrance.

PMID- 9191779
TI  - DMD-specific FISH probes are diagnostically useful in the detection of female
      carriers of DMD gene deletions.
AB  - The challenge of Duchenne muscular dystrophy (DMD) carrier identification resides
      in the ability to identify the presence of a mutant gene over the background
      contributed by the normal allele. Current diagnosis of carrier status when a
      deletion has been identified in a proband is based on an analysis of a gene
      dosage. We present a diagnostic strategy that uses fluorescence in situ
      hybridization (FISH) to detect female carriers with major deletions in the
      dystrophin gene. We screened a human X-chromosome-derived genomic library with a
      full-length dystrophin cDNA and isolated 15 dystrophin-specific cosmids that
      contain DMD gene exons. Six cosmids were further tested as FISH probes in control
      individuals and subsequently applied on chromosomes from eight males with DMD and
      known deletions and on samples from three female carriers. As expected, X
      chromosomes in normal females displayed four signals, two for the DMD-specific
      probe and two for the X-chromosome centromeric probe. Hybridization on
      chromosomal spreads from carriers of deletions revealed only one signal from the
      DMD-specific probe and two from the control centromeric probe. Males carrying
      deletions showed no DMD-specific signal for the deleted exons tested. Our data
      indicate that FISH could represent an alternative method for the detection of
      female carriers with DMD gene deletions.

PMID- 9191780
TI  - Reactivity of T cells from seronegative patients with myasthenia gravis to T cell
      epitopes of the human acetylcholine receptor.
AB  - Seronegative (SN) patients with myasthenia gravis (MG) have clinical and
      electrophysiologic features similar to those of seropositive (SP) patients, and
      they respond to the same therapeutic measures. However, because SN patients lack
      detectable (by standard radioimmunoassays) serum antibodies to acetylcholine
      receptor (AChR), which are considered to have a crucial role in MG, the
      pathophysiologic basis for the disease is not clear. We therefore compared the
      ability of peripheral blood lymphocytes (PBL) of SN patients (11) and SP patients
      (39) to respond to myasthenogenic T cell epitopes of human AChR. We tested two
      aspects that relate to T-cell immunity: 1) T cell responses to myasthenogenic
      peptides by proliferation and IL-2 production, and 2) the ability of antigen
      presenting cells to bind these T-cell epitopes. T cells of SN patients did not
      differ from those of SP patients in their ability to respond and to bind the two
      human AChR-derived myasthenogenic peptides. This supports the belief that most SN
      patients indeed suffer from an autoimmune disease directed against the AChR. The
      presence of T-cell immunity in the absence of antibodies may emphasize the
      importance of AChR-specific T cells in MG.

PMID- 9191781
TI  - Th1 epitope repertoire on the alpha subunit of human muscle acetylcholine
      receptor in myasthenia gravis.
AB  - In myasthenia gravis (MG), CD4+ T helper cells recognize the muscle acetylcholine
      receptor (AChR) alpha subunit. We investigated the epitope repertoire of anti
      AChR blood CD4+ Th1 cells from 13 myasthenic patients and three healthy controls,
      using overlapping synthetic peptides screening the alpha subunit sequence and an
      enzyme-linked immunospot (ELISPOT) assay that detects antigen-induced interferon
      gamma secretion of individual Th1 cells. All patients recognized a pool of the
      alpha subunit peptides. All but one patient recognized numerous peptides. Each
      patient had an individual pattern of peptide recognition, but most or all
      patients recognized four sequences (residues 48-67, 101-137, 304-322, and 403
      437) that stimulated relatively large numbers of Th1 cells. They include
      previously identified "immunodominant" sequences recognized by AChR-specific CD4+
      T cell lines from myasthenic patients. Peptide 1-14 was also recognized
      frequently. The controls recognized, with a low precursor frequency, the peptide
      pool and a few peptides that frequently included the immunodominant sequences
      described above. The present results demonstrate that Th1 cells are involved in
      the anti-AChR response in MG and that their epitope repertoire is very complex.
      This indicates that when MG is clinically evident, the AChR itself is the
      sensitizing antigen and the target of the autoimmune Th1 cells, although it does
      not exclude that molecular mimicry between one AChR epitope and a microbial
      structure may have triggered this autoimmune response. Although the complexity of
      the Th1 repertoire suggests that development of specific immunosuppressive
      treatments targeted on epitopes recognized by autoimmune T cells will be
      difficult, the existence of immunodominant T epitope sequences might facilitate
      that task.

PMID- 9191782
TI  - Characterizing swallowing abnormalities in progressive supranuclear palsy.
AB  - The dysphagia that occurs as an early sign of progressive supranuclear palsy
      (PSP), and which may predispose patients to aspiration pneumonia, has never been
      fully characterized. We evaluated 27 patients (mean +/- SEM: age, 64.9 +/- 1
      years; symptom duration, 52 +/- 5 months) who met the clinical National Institute
      of Neurological Disorders and Stroke and Society for PSP (NINDS-SPSP) criteria
      for possible or probable PSP, with a swallowing questionnaire, an oral motor and
      speech examination, and either a modified barium swallow or ultrasound studies.
      Twenty-eight age- and sex-matched healthy controls (age, 65.6 +/- 1.5 years) were
      also evaluated with the questionnaire, oral examination, and the ultrasound
      study. We used ANOVA statistics to evaluate differences between groups;
      nonparametric correlations to assess associations between swallowing and motor
      and cognitive abnormalities; and logistic regression analysis to determine if the
      items of the questionnaire or oral examination predicted ultrasound or modified
      barium swallow abnormalities. While PSP patients had at least one complaint on
      the swallowing questionnaire (mean, 6.6), healthy controls had fewer and less
      relevant complaints (0.3). Patients with moderate-to-severe cognitive
      disabilities had significantly more complaints of dysphagia than those with mild
      or no impairment. PSP patients' oral motor skills and speech were mildly impaired
      but significantly different from those of controls. In the ultrasound studies,
      PSP patients had significantly fewer continuous swallows and required a longer
      duration to complete their swallows than did healthy controls. They also had mild
      to-moderate abnormalities in the modified barium swallow study. The swallowing
      questionnaire, oral motor examination, and speech production examination
      accurately predicted the abnormalities detected with the swallowing studies.
      While 75% of patients had abnormal speech, all but one had abnormal swallowing
      studies. Thus, although dysphagia is associated with dysarthria, the two
      conditions are not always paired in the same patient. Our results suggest that
      the swallowing questionnaire and oral motor examination are an easy and cost
      effective method to predict the swallowing disturbances in PSP.

PMID- 9191783
TI  - Somatosensory evoked potentials in adrenomyeloneuropathy.
AB  - Adrenomyeloneuropathy (AMN) is an X-linked metabolic disorder causing
      accumulation of very-long-chain fatty acids with multifocal nervous system
      demyelination of the peripheral nerves, spinal cord, and cerebrum. The extent to
      which the disorder affects upper versus lower limbs or peripheral versus CNS has
      not been electrophysiologically defined in a large population nor differentiated
      in men and women. To determine patterns of nervous system demyelination and
      define gender differences, we studied 83 AMN patients with short latency median
      and posterior tibial nerve somatosensory evoked potentials (SSEPs). Most women
      (10/16) had abnormal median SSEPs all involving central pathways, whereas most
      men (59/67) had abnormal median SSEPs involving both peripheral and central
      pathways. Tibial SSEPs were abnormal in both sexes (14/15 women, 67/67 men), with
      either peripheral or central pathway involvement. This study demonstrates the
      frequent widespread involvement of both peripheral nerve and central
      somatosensory pathways in men with AMN and the predominantly central involvement
      in women.

PMID- 9191784
TI  - A trinucleotide deletion in the transthyretin gene (delta V 122) in a kindred
      with familial amyloidotic polyneuropathy.
AB  - A 63-year-old white man of Ecuadorian origin had a subarachnoid hemorrhage at age
      57 followed by numbness and paresthesia in his lower extremities. He subsequently
      developed sexual impotence, alternating constipation and diarrhea, urinary
      frequency, and difficulty in walking. Rectal biopsy revealed amyloid deposits
      immunohistochemically reactive with antitransthyretin antisera. Direct DNA
      sequencing of the transthyretin gene of the patient showed a trinucleotide
      deletion in exon 4. This deletion resulted in the loss of one of two valines at
      position 121 or 122. DNA analysis on 11 family members at risk revealed four
      mutant gene carriers. Plasma transthyretin levels in the mutant gene carriers
      measured by nephelometry were very low. Peptide sequence analysis revealed that
      most of plasma transthyretin was normal with only a small amount of variant
      protein. This is the first report of a DNA deletion in the transthyretin gene. We
      speculate that the loss of valine in the carboxyl terminal region of the
      transthyretin monomer alters stability of the tetrameric protein, which leads to
      rapid clearance from the plasma and amyloid deposition in the tissue.

PMID- 9191785
TI  - Lymphoproliferative disorders and motor neuron disease: an update.
AB  - We studied 26 patients with both motor neuron disease and lymphoproliferative
      disease (LPD). Twenty-three patients had definite or probable upper motor neuron
      signs; none had electrophysiologic evidence of motor neuropathy. LPD syndromes
      comprised Waldenstrom's macroglobulinemia, multiple myeloma, chronic lymphocytic
      leukemia, follicular cell lymphoma, and Hodgkin's disease. In all but one
      patient, the cause of disability or death was neurologic. LPD was confined to
      bone marrow in 14 patients; eight of 14 had monoclonal paraproteinemia. One
      patient had LPD discovered at autopsy. Treatment of LPD in 20 patients resulted
      in neurologic improvement in 1 patient and arrest in another; both had
      progressive spinal muscular atrophy. Eleven patients were worse and 13 died. At
      least 30 cases have been reported from other centers, bringing the total to 56.
      Among the unusual reported concomitants were POEMS (polyneuropathy, organomegaly,
      endocrinopathy, myeloma, and skin changes) syndrome of myeloma and angiotropic
      lymphoma.

PMID- 9191786
TI  - Acute intermittent porphyria: clinicopathologic correlation. Report of a case and
      review of the literature.
AB  - Acute intermittent porphyria (AIP), an autosomal dominant disorder, results from
      a deficiency of the enzyme hydroxymethylbilane synthase. Despite important
      advances in the characterization of AIP, the pathophysiology of the neurologic
      manifestations is not clearly understood. We present a patient with AIP followed
      for 31 years with multiple episodes of hyponatremia during AIP exacerbations. We
      discuss the clinicopathologic correlation and possible explanations for the
      morphologic findings, including discrete hypothalamic changes.

PMID- 9191787
TI  - Hereditary thermosensitive neuropathy: an autosomal dominant disorder of the
      peripheral nervous system.
AB  - We report the clinical and electrophysiologic characteristics of eight patients
      (four men and four women) with a hereditary neuropathy with probable
      thermosensitivity (HTN) of autosomal dominant inheritance. Patients presented
      reversible episodes of ascending muscle weakness, paresthesiae, and areflexia
      apparently triggered by an elevation of body temperature over 38.5 degrees C.
      Mean age at onset was 13 +/- 12 (SD; range 6 to 43). Four patients had suffered
      up to five attacks. EMG and pathologic findings were compatible with a reversible
      demyelinating neuropathy such as Guillain-Barre syndrome. We excluded loci
      causing other hereditary demyelinating neuropathies, such as Charcot-Marie-Tooth
      disease type I (CMT type I) and hereditary neuropathy with liability to pressure
      palsies (HNPP), by linkage analysis; thus, HTN is not allelic to either CMT type
      I or to HNPP.

PMID- 9191788
TI  - Chronic relapsing axonal neuropathy responsive to intravenous immunoglobulin.
AB  - Chronic relapsing axonal neuropathy is uncommon. I describe a 68-year-old patient
      who responded rapidly and repeatedly to intravenous immunoglobulin treatment.

PMID- 9191789
TI  - Axonal pathology in Japanese Guillain-Barre syndrome: a study of 15 autopsied
      cases.
AB  - We assessed the frequency and extent of axonal involvement in the ventral spinal
      roots in 15 Japanese autopsied patients with Guillain-Barre syndrome (GBS).
      Teased-fiber preparation revealed that five had predominantly axonal pathology
      with minimal segmental demyelination, seven had predominantly segmental
      demyelination with minimal axonal changes, two patients showed a mixture of both
      conditions, and one patient did not show any particular pathologic changes. We
      confirmed axon loss by immunohistochemical analysis of high-molecular-weight
      neurofilament protein. Macrophage invasion was a prominent feature in nerves with
      predominantly axonal changes. Two patients with severe axonal involvement and
      prolonged clinical courses exhibited motor neuron loss with astrogliosis in the
      ventral horns. These results suggest that autopsy-verified axonal involvement is
      more frequent among Japanese GBS patients than in Caucasian populations but less
      frequent than that reported from northern China.

PMID- 9191790
TI  - Band heterotopia or double cortex in a male: bridging structures suggest
      abnormality of the radial glial guide system.
AB  - A moderately retarded Japanese boy, with a normal male karyotype (46,XY), was
      diagnosed to have a subcortical band heterotopia or double cortex syndrome. The
      band heterotopia was relatively thick compared with that of other patients
      reported. On T2-weighted coronal MR sections, there were numerous radial linear
      structures between the cortex and the band, probably representing the trace of
      radial fibers. He had no family members with seizures or mental retardation. Over
      50 described patients with this malformation have been female except two patients
      briefly mentioned by several investigators. Band heterotopia or the double cortex
      syndrome is inherited as a sex-linked dominant condition. Affected mothers may
      have affected daughters or sons with lissencephaly, suggesting a link between
      these disorders. This is the first detailed description of a male with band
      heterotopia.

PMID- 9191791
TI  - Chemotherapy of human malignant glioma: prevention of efficacy by dexamethasone?
AB  - Steroids are commonly administered for the control of edema, mass effect, and
      side effects from therapy to patients with malignant glioma who are receiving
      radiotherapy and chemotherapy. Here, we report that therapeutic concentrations of
      dexamethasone (DEX) attenuate cytotoxicity and growth inhibition of human
      malignant glioma cells induced by exposure to several chemotherapeutics,
      including ACNU, VM-26, vincristine, cytarabine, methotrexate, and adriamycin. DEX
      mediated cytoprotection is not linked to DEX effects on glioma cell
      proliferation. However, the cytoprotective effects of DEX appeared to be more
      prominent in cell lines with wild-type p53 status (n = 2) than in p53 mutant cell
      lines (n = 3). Further, DEX-mediated rescue from chemotherapy does not directly
      involve Bcl-2 family proteins since DEX failed to change the expression of Bcl-2
      or Bax proteins and since bcl-2 gene transfer-mediated cytoprotection was not
      redundant with the effects of DEX. DEX thus appears to control a common, bcl-2
      independent death pathway in glioma cells that is not limited to specific drug
      actions. Chemotherapy is usually given as an elective, adjuvant treatment to
      glioma patients in stable condition who can tolerate steroid withdrawal. To
      maximize therapeutic efficacy, steroids should be withdrawn from glioma patients
      prior to chemotherapy.

PMID- 9191792
TI  - Chondrosarcoma of the spine and thyroid carcinoma following radiation therapy for
      Hodgkin's lymphoma.
AB  - Second malignant neoplasms are an infrequent but well-documented sequelae of
      radiation therapy for childhood cancer. We report a 34-year-old man with
      chondrosarcoma of the spine and thyroid carcinoma diagnosed 24 years after
      radiation therapy for Hodgkin's lymphoma. Both tumors arose in the previously
      irradiated field and were not detected until the patient presented with
      paraplegia. The propensity of these neoplasms to arise in the previously
      irradiated field warrants physicians to be alert to any manifestations arising in
      this anatomic area.

PMID- 9191793
TI  - Bradycardia and asystole induced by partial seizures: a case report and
      literature review.
AB  - Bradyarrhythmias associated with partial seizures are uncommon, with most
      reported patients having temporal lobe seizure foci on scalp EEG recordings. We
      report a patient with bradycardia and sinus arrest during a complex partial
      seizure documented during bilateral subdural EEG and EEG and simultaneous video
      and EEG recordings. The seizure began in the left temporal lobe and spread to the
      right temporal region, with bradycardia occurring 55 seconds after ictal onset
      and asystole after 60 seconds.

PMID- 9191794
TI  - Clinical effectiveness of lamotrigine and plasma levels in essential and
      symptomatic trigeminal neuralgia.
AB  - This paper reports on the effectiveness of oral lamotrigine in 15 patients
      suffering from "essential" trigeminal neuralgia and in five patients suffering
      symptomatic trigeminal neuralgia concomitant with multiple sclerosis. We recorded
      objective and subjective pain ratings and correlated them to daily dosage (400 mg
      maximum) and plasma levels of the drug. We detected pain relief proportional to
      daily dosage and to drug plasma levels. Eleven of the cases affected by the
      "essential" form of neuralgia showed complete pain relief on reaching their
      maximum daily dosage. All cases affected by the symptomatic form had complete
      pain relief. We could detect no changes from these results by the end of the
      follow-up period (3 to 8 months after the study ended).

PMID- 9191795
TI  - Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) patients suffer from disabling physical and mental
      fatigue. Circulating autoimmune antibodies may produce symptoms of muscular
      fatigue by reacting with acetylcholine receptors or calcium binding channels.
      They can also produce mental status changes by reacting with central nervous
      system (CNS) antigens. We thoroughly investigated the presence of circulating
      antimuscle and anti-CNS antibodies in 10 CFS patients and 10 controls. We were
      unable to detect any pathogenic antibodies.

PMID- 9191796
TI  - Further evidence supporting linkage of hereditary neuralgic amyotrophy to
      chromosome 17q.
AB  - Hereditary neuralgic amyotrophy is a rare autosomal dominant disorder of the
      peripheral nervous system. Previous segregation analysis in two large pedigrees
      suggested linkage to distal 17q. Linkage data obtained in the present study
      investigating a three generation pedigree confirm linkage to 17q24-q25.

PMID- 9191797
TI  - The role of technology in neurologic specialization in America.

PMID- 9191798
TI  - Carpet carrier's palsy: musculocutaneous neuropathy.

PMID- 9191799
TI  - Neurologic complications of lumbar epidural analgesia: spinal and paraspinal
      abscess.

PMID- 9191800
TI  - Around the WORLD backward: an algorithm for scoring the MMSE WORLD item.

PMID- 9191801
TI  - Posttraumatic headache.

PMID- 9191802
TI  - Posttraumatic headache.

PMID- 9191803
TI  - Pure transient amnesia during nonconvulsive status epilepticus.

PMID- 9191804
TI  - Pure transient amnesia during nonconvulsive status epilepticus.

PMID- 9191805
TI  - Treatment with fetal allografts.

PMID- 9191806
TI  - Myofascial pain and fibromyalgia syndromes.

PMID- 9191807
TI  - Myofascial pain and fibromyalgia syndrome.

PMID- 9191808
TI  - Myofascial pain and fibromyalgia syndrome.

PMID- 9191809
TI  - Myofascial pain and fibromyalgia syndrome.

PMID- 9191810
TI  - Myofascial pain and fibromyalgia syndrome.

PMID- 9191811
TI  - Myofascial pain and fibromyalgia syndrome.

PMID- 9191812
TI  - Endarterectomy on asymptomatic patients.

PMID- 9191813
TI  - Endarterectomy on asymptomatic patients.

PMID- 9191814
TI  - Clearing up misunderstandings about clinical trial methodology: a reply to
      Barnett et al.'s commentary on the ACAS Trial. ACAS Executive Committee, ACAS
      Data and Safety Monitoring Committee.

PMID- 9191815
TI  - G-pers creepers, where'd you get those papers? A reassessment of the literature
      on the hepatitis G virus.

PMID- 9191816
TI  - Early changes in hemoglobin and hematocrit levels after packed red cell
      transfusion in patients with acute anemia.
AB  - BACKGROUND: Equilibration of hemoglobin concentration after transfusion has been
      estimated to take about 24 hours, but some studies have shown that earlier
      measurements reflect steady-state values in persons who have not bled recently.
      This study was aimed at assessing the changes over time in hemoglobin
      concentration after transfusion in acutely anemic patients because of recent
      bleeding. STUDY DESIGN AND METHODS: Thirty-two normovolemic patients recovering
      from an acute bleeding episode who were no longer thought to be bleeding and who
      received a 2-unit red cell transfusion were studied. At baseline and 15, 30, 60,
      and 120 minutes and 24 hours after transfusion, hemoglobin concentration and
      hematocrit values were measured. RESULTS: The administration of 2 units of packed
      red cells elicited a 24-hour increase of 22.4 +/- 6.8 g per L in hemoglobin
      concentration. Hemoglobin values were not different at any of the defined
      posttransfusion times. Hematocrit levels experienced similar changes over time.
      Agreement between 15-minute and 24-hour values was excellent, as only 6 percent
      of patients exhibited a clinically significant difference (> 6 g/L) between the
      hemoglobin measurements. CONCLUSION: Hemoglobin and hematocrit values rapidly
      equilibrate after transfusion in normovolemic patients who are recovering from an
      acute bleeding episode. This fact would allow a rapid assessment of the effects
      of transfusion and of the recurrence of bleeding in patients remaining at risk.

PMID- 9191817
TI  - Effectiveness of a prospective physician self-audit transfusion-monitoring
      system.
AB  - BACKGROUND: The purpose of this study was to search for a more effective
      transfusion-monitoring system than the existing system of retrospective peer
      review. STUDY DESIGN AND METHODS: This research used a study-control,
      preintervention and postintervention design, to evaluate the effectiveness of a
      prospective physician self-audit transfusion-monitoring system that functioned
      without the direct involvement of transfusion service physicians. This research
      also evaluated the effectiveness of issuing to physicians a memo with transfusion
      guidelines. Three process indicators were used to assess physician behavior at
      various stages of the blood-ordering process: 1) the number of crossmatches
      ordered per admission, 2) the transfusion-to-crossmatch ratio, and 3) the number
      of blood units returned to the laboratory after physician self-auditing. The
      study used two outcome indicators to reflect overall blood utilization: 1) the
      percentage of patients who received red cell transfusions and 2) the number of
      blood units transfused per recipient each month. RESULTS: The prospective
      physician self-audit system implemented at the study hospital did not reverse
      physician transfusion decisions, and the process of issuing to physicians a memo
      with transfusion guidelines at the control hospital failed to reduce blood usage.
      However, a transient reduction in blood utilization was observed at the study
      hospital. CONCLUSION: The reduction was hypothesized to be due to a Hawthorne
      effect, in which observed behavior is affected by the subject's awareness of the
      research study.

PMID- 9191818
TI  - Liquid nitrogen freezers: a potential source of microbial contamination of
      hematopoietic stem cell components.
AB  - BACKGROUND: The recent report of hepatitis B transmission between hematopoietic
      progenitor and putative stem cell (HPC) components stored in liquid nitrogen led
      to the questioning of whether evidence existed for similar contamination by
      bacterial or fungal elements. STUDY DESIGN AND METHODS: Microbial contamination
      rates were reviewed for 704 HPC components from 255 patients over an 18-month
      period. Five liquid nitrogen freezers were surveyed for microbial contamination.
      The literature was reviewed to ascertain the published experience of other
      laboratories with HPC component contamination first documented on thawing.
      RESULTS: Seven (1.2%) of 583 thawed components were found to be contaminated with
      a variety of environmental or waterborne organisms, despite a meticulous protocol
      to prevent contamination during thawing. All of these components had been sterile
      on cryopreservation. Literature review revealed a similar incidence of post-thaw
      contamination from other centers. Microbial survey of liquid nitrogen freezers
      revealed low-level contamination in four of five. The organisms represented were
      similar to those cultured from thawed HPC components. One freezer was heavily
      contaminated by Aspergillus species. CONCLUSION: Liquid nitrogen freezers are not
      sterile, and both the liquid and vapor phases are potential sources of microbial
      contamination of HPC components. While low-level contamination by environmental
      organisms may be common, the occurrence of heavy contamination by potential
      pathogens such as Aspergillus species suggests that monitoring of liquid nitrogen
      sterility may be indicated. Strategies to assess and prevent microbial
      transmission from liquid nitrogen to HPC components need further development.

PMID- 9191819
TI  - Shelf-life of photodynamically sterilized red cell concentrates with various
      numbers of white cells.
AB  - BACKGROUND: Phthalocyanines are useful sensitizers for the photodynamic
      sterilization of red cell concentrates. The use of the phthalocyanine Pc4
      (HOSiPcOSi(CH3)2(CH2)3N(CH3)2) and red light is very efficient in killing various
      viruses. The addition of scavengers of Type I photodynamic reactions and the use
      of cremophor to deliver Pc4 give protection to the red cells. STUDY DESIGN AND
      METHODS: Various red cell components, either white cell-enriched, buffy coat
      removed, or white cell-reduced, have been used to study the effect of
      photodynamic treatment with Pc4 on hemoglobin and potassium leakage and on ATP
      and glucose levels after prolonged storage. RESULTS: After treatment, storage
      interval-dependent damage to the red cells could be observed. In components with
      26 x 10(9) white cells per L, virus inactivation was less efficient than that in
      components with no or 2 x 10(9) white cells per L. Similarly, red cells were less
      affected by the treatment in components with a large number of white cells.
      Pretreatment storage and use within 1 week after photodynamic treatment induce
      less damage to the red cells at the moment of transfusion. CONCLUSION: Various
      improvements in the treatment protocol may ultimately lead to the implementation
      of photodynamic treatment in transfusion practice. In this respect, the white
      cell content of the red cell concentrates should be taken into account.

PMID- 9191820
TI  - Microdroplet fluorochromatic assay for the enumeration of white cells (WBCs) in
      WBC-reduced blood components: validation and application for evaluating newly
      developed WBC-reduction filters.
AB  - BACKGROUND: Sensitive and accurate counting methods are required to assess the
      residual white cells (WBCs) in WBC-reduced blood components. The Nageotte
      hemocytometer, widely used for this purpose, is cumbersome, and its efficacy is
      dependent upon the skill of the operator. The performance of a simple
      fluorochromatic assay using tissue-typing microdroplet trays is presented here.
      STUDY DESIGN AND METHODS: Undiluted samples of blood components were mixed with a
      fluorochromatic dye in trays. WBCs were counted under an epifluorescence
      microscope. The accuracy and sensitivity of this method were compared with those
      of the reference Nageotte hemocytometer method by using serial dilution of
      samples of platelets and red cells containing known concentrations of WBCs and by
      calculating the standard curves. The Nageotte hemocytometer and the microdroplet
      fluorochromatic assay (MFA) were also compared in terms of count correlation and
      reproducibility in 320 paired counts of plateletpheresis samples. MFA was used to
      evaluate a newly developed WBC-reduction red cell filter. RESULTS: The MFA for
      platelets and red cells was linear to 0.1 and 0.03 WBCs per microL, respectively.
      The linear regression line of log10 MFA versus log10 Nageotte method had a slope
      of 0.963, intercept of -0.04, and r2 of 0.968. The Nageotte method gave an
      estimation of WBC content 12 to 20 percent greater than that of the MFA. The MFA,
      with a larger neat sample volume, showed precision comparable to that of the
      Nageotte method. The filters demonstrated a median WBC reduction of 4.8 log10.
      CONCLUSION: The MFA is a sensitive and accurate method for quality control
      processes to assess the residual WBCs in WBC-reduced blood components.

PMID- 9191821
TI  - Blood group antigens Rb(a), Tr(a), and Wd(a) are located in the third ectoplasmic
      loop of erythroid band 3.
AB  - BACKGROUND: Rb(a), Tr(a), and Wd(a) are three low-incidence blood group antigens
      that have not been assigned to a particular structure of the red cell membrane.
      Recent genetic and serologic data suggested erythroid band 3 as a possible
      carrier of these three antigens. STUDY DESIGN AND METHODS: Ten band 3 gene exons
      that encode the membrane domain of band 3 were screened for single strand
      conformation polymorphism (SSCP). Exons displaying SSCP were cloned and
      sequenced, and the presence of the mutations was verified by restriction
      digestion. RESULTS: Substitutions 548 Pro-->Leu, 551 Lys-->Asn, and 557 Val-
      >Met, all located in the third ectoplasmic loop of band 3, were detected in the
      subjects with Rb(a+), Tr(a+), and Wd(a+) red cells, respectively. The presence of
      the Rb(a) and Wd(a) mutations was confirmed in additional carriers of these blood
      group antigens. Chymotryptic cleavage at Tyr 553 and Tyr 555 abolished the
      agglutinability of Tr(a+) and Wd(a+) cells with the corresponding antisera,
      further demonstrating that the epitopes are located in the third ectoplasmic loop
      of band 3. Similar quantities of mRNA corresponding of the two band 3 alleles, a
      normal pattern of red cell membrane proteins, and normal DIDS (4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid, disodium salt)-inhibitable
      sulfate flux were detected, which suggests that the mutations do not affect band
      3 mRNA stability or band 3 protein expression and transport function. CONCLUSION:
      Wd(a) and Rb(a), and tentatively Tr(a), can be assigned to the Diego blood group
      system.

PMID- 9191822
TI  - Lower antigen site density and weak D immunogenicity cannot be explained by
      structural genomic abnormalities or regulatory defects of the RHD gene.
AB  - BACKGROUND: The weak D phenotype is characterized serologically by a weak or
      negative agglutination reaction with polyclonal anti-D in an immediate-spin test.
      Agglutination is enhanced in the indirect antiglobulin test. Red cells that are
      typed weak D have a much lower number of apparently complete D antigens at their
      cell surface and are associated with considerably weaker immunogenicity than are
      red cells with normal D. In a previous study, the number of D sites per cell was
      determined in eight unrelated weak D individuals to range from 490 to 1870 D
      sites per cell, which corresponded to 4 to 14.2 percent of the number of D sites
      in CcDee samples. STUDY DESIGN AND METHODS: The RHD gene was investigated for
      structural abnormalities by Southern blot experiments and polymerase chain
      reaction-based RHD typing in these individuals. In addition, abnormalities in the
      transcription process were studied by sequence analysis of RH transcripts and by
      comparing the relative amounts of RHD mRNA in weak D to those in CcDee, CcDEe,
      and -D- samples by using a semiquantitative reverse transcriptase-polymerase
      chain reaction analysis. RESULTS: The RHD gene in weak D phenotypes does not show
      any abnormalities at either the genomic or the transcriptional level when
      compared to the RHD gene in normal D phenotypes. CONCLUSION: The weaker
      immunogenicity of weak D is not explained by structural difference in the RHD
      gene itself. The weaker expression of D might be caused by factors involved in
      the Rh-related complex or by an as yet unidentified suppressor gene. This study
      supports the concept that weak D phenotypes carry complete D polypeptides and
      reflect a quantitative rather than a qualitative variation of D.

PMID- 9191823
TI  - Crossmatch-compatible platelets improve corrected count increments in patients
      who are refractory to randomly selected platelets.
AB  - BACKGROUND: HLA-matched platelets and crossmatch-compatible platelets are used to
      support thrombocytopenic patients who are refractory to randomly selected
      platelets. Data supporting the effectiveness of crossmatch-compatible platelets
      are limited, being essentially restricted to the subset of refractory patients
      previously shown to be alloimmunized. The authors' hospital does not test for
      alloimmunization. To determine the effectiveness of crossmatch-compatible
      platelets in an unselected group of refractory patients, the use of such
      platelets for all patients who are refractory to random-donor platelets was
      reviewed. STUDY DESIGN AND METHODS: All patients who received crossmatch
      compatible platelets between January 1991 and May 1994 were retrospectively
      reviewed. All study patients were refractory to random-donor platelets, having
      two consecutive corrected count increments (CCIs) of < 10,000. A solid-phase red
      cell adherence method was used for platelet crossmatching, and CCI was used to
      monitor the effectiveness of each platelet transfusion. RESULTS: A total of 475
      crossmatch-compatible platelet components were administered to 66 evaluable
      patients who were refractory to random-donor platelets. A significant improvement
      was found in the mean CCI when crossmatch-compatible platelets were compared with
      randomly selected platelets (p < 0.0001): an increase of 8000 +/- 6100 (mean +/-
      SD). In 59 percent (39/ 66) of the patients, the mean CCI improved to at least
      7,500 and in 41 percent (27/66) to at least 10,000. If the 10 patients for whom
      crossmatch-compatible platelets were not identified are included, the mean CCI in
      51 percent (37/76) of the refractory patients improved to at least 7,500; in 36
      percent (27/76), it improved to at least 10,000. The effectiveness of crossmatch
      compatible platelets did not decline with continued use. CONCLUSION: Crossmatch
      compatible platelet components significantly improve the mean CCI for
      approximately one-half of patients who are refractory to random-donor platelets,
      even when the patients are not preselected for having alloimmunization to explain
      their refractory state.

PMID- 9191824
TI  - The COBE Spectra cell separator is more effective than the Haemonetics MCS-3P
      cell separator for peripheral blood progenitor cell harvest after mobilization
      with cyclophosphamide and filgrastim.
AB  - BACKGROUND: Peripheral blood is rapidly replacing bone marrow as a source of
      hematopoietic progenitor cells for autologous transplantation. The advantages of
      peripheral blood progenitor cell transplantation are enhanced by the ability to
      collect sufficient progenitor cells to ensure rapid neutrophil and platelet
      recovery in a single procedure on some cell separators. STUDY DESIGN AND METHODS:
      A prospective randomized study was undertaken to compare peripheral blood
      progenitor cell yields from two cell separators (MCS-3P, Haemonetics and Spectra,
      COBE). Fifteen consecutive patients were mobilized with cyclophosphamide 2 g per
      m2 (Day 0) and filgrastim 10 micrograms per kg (Days 1-11). Consecutive
      collections (Day 10, Day 11) were performed with each machine once: patients were
      randomly assigned to either machine for the initial collection. RESULTS:
      Collection time was longer on the MCS-3P (p = 0.001), and the volume processed
      was greater with the Spectra (p < 0.0001). Despite similar nucleated cell yield
      (p = 0.62), the yield of CD34+ cells (p = 0.001) and colony-forming units
      granulocytic-monocytic (p = 0.0001) was significantly higher with the Spectra.
      The yield of nucleated cells per unit of blood volume processed was higher for
      the MCS-3P (p = 0.0007), while the CD34+ cell yield (p = 1) and colony-forming
      units-granulocytic-monocytic yield (p = 1) per unit of blood volume processed
      were similar for the two machines. The collection of CD34+ cells at levels > 2 x
      10(6) per kg (p = 0.063), 5 x 10(6) per kg (p = 0.031), and colony-forming units
      granulocytic-monocytic > 1 x 10(5) per kg (p = 0.25) after a single collection
      was superior for the Spectra. CONCLUSION: The yield of progenitor cells after
      collection on the Spectra was superior to that achieved with the MCS-3P, because
      of the larger volume of blood processed per procedure. This would permit more
      patients to undergo only one collection.

PMID- 9191825
TI  - A method for estimating hepatitis B virus incidence rates in volunteer blood
      donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor
      Study.
AB  - BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections
      in the blood donor setting that are based solely on data for seroconversion to
      hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the
      transient nature of antigenemia. Estimates based on antibody to hepatitis B core
      antigen will overestimate the incidence due to false-positive results caused by
      the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results
      were obtained from multiple-time volunteer donors at five United States blood
      centers from January 1991 through December 1993. The observed HBsAg
      seroconversion rate was multiplied by an adjustment factor, derived from the
      weighted average probability of a positive HBsAg test for HBV-infected donors who
      become chronic carriers, for donors with a primary antibody response without
      detectable antigenemia, and for donors who develop transient antigenemia.
      RESULTS: Among 586,507 multiple-time donors giving 2,318,356 donations and
      observed for 822,426 person-years, the HBsAg incidence rate was 4.01 per 100,000
      person-years. On the basis of prior reports of the duration of HBsAg positivity
      and the observed distribution of interdonation intervals among the study group,
      there was an estimated 53-percent chance that an HBV-infected donor with
      transient antigenemia would have a positive HBsAg test result. If 70 percent of
      newly HBV-infected adults have transient antigenemia, 25 percent have a primary
      antibody response without primary antigenemia, and 5 percent become chronic
      carriers, the overall chance of being detected by the HBsAg test was 42 percent,
      for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was
      estimated to be 9.54 per 100,000 person-years. CONCLUSION: The crude HBV
      incidence rate observed from HBsAg test results will underestimate the true rate.
      The adjusted HBV incidence rate should be used in applications such as
      estimations of residual HBV risk to the blood supply and projections of the
      benefits of screening for HBV DNA.

PMID- 9191826
TI  - Role of screening for hepatitis C virus in children with malignant disease and
      who undergo bone marrow transplantation.
AB  - BACKGROUND: Children with malignant disease who received multiple blood
      transfusions before the clinical definition of hepatitis C virus (HCV) require
      evaluation for HCV infection. STUDY DESIGN AND METHODS: The role of HCV infection
      in 54 children with primary malignant disease was evaluated in terms of the
      following aspects: prevalence of HCV infection, distribution of HCV subtype, the
      benefit of screening of blood donors, and the presence of chronic liver disease.
      The benefit of screening for HCV in a subset of patients who underwent bone
      marrow transplantation (BMT) was also evaluated. RESULTS: Seventeen patients
      (31.4%) of 54 tested were seropositive in a second-generation HCV antibody test.
      Thirteen patients (24.0%) were also positive for circulating HCV RNA. HCV subtype
      1b and HCV subtype 2b were found in six and two patients, respectively. Multiple
      HCV genotypes were present in two patients. One of these two patients had
      relatively progressive liver disease. Before the introduction of blood screening
      with a second-generation HCV antibody test, 15 of 35 patients seroconverted,
      whereas none of 7 patients seroconverted after the screening was used (p =
      0.032). For patients who underwent BMT, the screening drastically decreased the
      seroconversion rate, from 7 of 11 patients to 0 of 6 (p = 0.016). CONCLUSION: A
      considerable number of children with primary malignant disease who received
      multiple blood transfusions became infected by HCV before HCV screening was used.
      Patients who underwent BMT were at high risk for HCV infection. Screening with a
      second-generation HCV antibody test has proven to be remarkably beneficial in
      preventing HCV infection in these children.

PMID- 9191827
TI  - Prevalence of hepatitis G virus RNA in French blood donors and recipients.
AB  - BACKGROUND: Recently, cases of chronic hepatitis were linked to the presence of
      genomic sequences of a newly described RNA virus termed hepatitis G virus (HGV)
      and belonging to the Flaviviridae family. STUDY DESIGN AND METHODS: The presence
      of HGV RNA was searched for by polymerase chain reaction in a population of blood
      donors and in patients who had received multiple blood component transfusions
      and/or intravenous immunoglobulin (IVIG) infusions. RESULTS: Twenty-one (4.2%) of
      500 donors were positive for HGV RNA as were 21 (10.7%) of 196
      nonimmunosuppressed patients who had received multiple transfusions of packed red
      cells, 4 (8.7%) of 46 common variable immune deficiency (CVID) patients who had
      received only IVIG, and 22 (24.7%) of 89 bone marrow transplant (BMT) patients
      who had received IVIG and cellular components. The proportion of HGV-positive
      individuals was significantly higher in the immunosuppressed recipients (CVID and
      BMT patients) than in the nonimmunosuppressed patients who were multiply
      transfused with packed red cells (p < 0.03). The proportion of HGV-positive
      individuals was significantly higher in the BMT patients who had received IVIG
      and cellular components than in the CVID patients who had received IVIG only (p <
      0.03). Eight (17.0%) of the 47 HGV-positive recipients and 48 (16.9%) of the 284
      HGV-negative recipients had a serum alanine aminotransferase level higher than
      the upper limit of normal (nonsignificant difference). The medical history of HGV
      positive donors failed to reveal a particular at-risk event. The large majority
      of HGV-infected patients had a normal serum alanine aminotransferase level, and
      the proportion of patients with elevated alanine aminotransferase was the same in
      HGV-positive and in HGV-negative recipients. CONCLUSION: The pathological
      significance of HGV infection remains unelucidated, and the classification of HGV
      as a new hepatitis virus was perhaps premature.

PMID- 9191828
TI  - Prevalence of hepatitis G virus and its strain variant, the GB agent, in blood
      donations and their transmission to recipients.
AB  - BACKGROUND: Hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C)
      are independent isolates of a recently identified non-A through -E hepatitis
      virus. Prevalence in United States volunteer blood donors is 1.5 to 1.9 percent,
      but no data on European blood donors are available. Epidemiologic data suggest a
      preferred parenteral transmission route. The prevalence of HGV/GBV-C in European
      blood donors and the efficiency of transmission to transfusion recipients were
      investigated. STUDY DESIGN AND METHODS: Plasma samples from unpaid volunteer
      German blood donors were tested for HGV/GBV-C by in-house reverse transcription
      polymerase chain reaction. Positive donors were independently retested and
      interviewed for parenteral transmission risks. Amplification products were
      sequenced and subjected to phylogenetic analysis. Recipients of reverse
      transcription-polymerase chain reaction-positive donations were traced and tested
      for HGV/GBV-C infection. RESULTS: A total of 14 (1.34%) of 1048 donors (alanine
      aminotransferase < 45 IU/L) were repeatedly positive for HGV/GBV-C with 9 (2.18%)
      of 413 urban and 5 (0.78%) of 635 rural donors (chi 2-test; p = 0.04). Isolates
      differed in nucleotide sequence homology over a range of 12.5 to 19.6 percent.
      All but one positive donor reported parenteral transmission risks. Transmission
      of HGV/GBV-C was detected in 4 of 9 transfusion recipients. The prevalence of
      HGV/GBV-C in donors with an alanine aminotransferase level > 45 IU per L was 3
      percent (3/100). Two mother/child pairs were identified with highly homologous
      isolates. CONCLUSION: A significantly greater prevalence of HGV/GBV-C was
      detected in urban volunteer blood donors than in rural donors. The high
      prevalence in urban donors (2.18%) suggests specific transmission risks for this
      group. The less than 50-percent efficiency of HGV/GBV-C transmission via blood
      components may indicate the presence of defective viruses with reduced
      infectivity. There is evidence for vertical transmission.

PMID- 9191829
TI  - Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C),
      among blood donors in Japan.
AB  - BACKGROUND: The purpose of the study was to survey the epidemiology of recently
      reported non-A through -E hepatitis virus designated hepatitis G virus (HGV) and
      its strain variant, the GB agent (GBV-C). STUDY DESIGN AND METHODS: Pilot samples
      from 2461 blood donors in Japan, randomly selected to form cohorts with different
      levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or
      hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV-C by reverse
      transcription-polymerase chain reaction with nested primers deduced from the 5'
      noncoding region. RESULTS: HGV/GBV-C RNA was detected in 23 (7.4%) of the 361
      donors with anti-HCV and HCV RNA. This detection is more frequent than that in
      donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis
      B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46
      and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L
      (5/361; 1.4%), and donors with anti-HCV but without detectable HCV RNA (1/93;
      1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were
      infected with HGV/GBV-C, and the prevalence was much higher in those with HCV
      RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae,
      either alone or in concert with the other hepatitis viruses, screening of blood
      units for HGV/GBV-C would deserve consideration.

PMID- 9191831
TI  - Transfusion: the first decade: volume 6.

PMID- 9191832
TI  - Interpretation of false-positive human immunodeficiency virus type 1 western blot
      assays in blood donors.

PMID- 9191830
TI  - Early observations about the ABO blood groups.

PMID- 9191833
TI  - Very anemic donors may pass copper sulfate screening tests.

PMID- 9191834
TI  - Large-volume leukapheresis in pediatric patients.

PMID- 9191835
TI  - Recruitment of CD34+ cells during large-volume leukapheresis.

PMID- 9191837
TI  - Measles virus infection of human T cells modulates cytokine generation and IL-2
      receptor alpha chain expression.
AB  - Measles virus (MV) suppresses specific functions in cells of the immune system
      and causes a generalized immunosuppression by mechanisms which remain undefined.
      It has been previously established that mitogen-induced proliferation of
      peripheral blood mononuclear cells (PBMC) is suppressed by infection with MV. Our
      current study demonstrates that MV infection inhibits antigen-specific
      proliferation of T lymphocytes. The inhibition of proliferation was not due to a
      decrease in IL-2 production. IL-2 production in cultures of infected and
      uninfected antigen-specific T cells was similar. In contrast, we found that
      expression of the IL-2R alpha subunit was decreased in mitogen-stimulated, MV
      infected PBMC and antigen-stimulated, MV-infected T lymphocytes compared to
      stimulated but noninfected T cells. However, the expression of the IL-2R beta
      subunit was not altered in MV-infected T cells. We also examined the influence of
      MV infection on the production of the cytokines IL-4, IL-6, IL-10, and IFN-gamma
      by T lymphocytes. By comparing infected versus uninfected antigen-specific T cell
      lines, we found that MV infection of antigen-specific activated T cells caused no
      substantial change in generation of IFN-gamma, IL-6, or IL-10. There was a 50%
      reduction in IL-4 generation following MV infection. These data indicate that the
      immunosuppression by acute MV infection is not associated with a generalized
      inhibition of cytokine production. One mechanism for the suppression of
      proliferation following acute MV infection may be a block in the expression of
      the IL-2R alpha subunit by activated T cells.

PMID- 9191838
TI  - Replication signals in the genome of vesicular stomatitis virus and its defective
      interfering particles: identification of a sequence element that enhances DI RNA
      replication.
AB  - We have analyzed the role of terminal sequences of a defective interfering (DI)
      particle RNA of vesicular stomatitis virus (VSV) in replication. A series of
      internal deletion mutants of DI cDNA was generated to obtain DI genomic RNAs that
      differed from one another by the presence of different lengths of 3'-terminal
      and/or 5'-terminal sequences. Analyses of the mutant. RNAs for their ability to
      replicate in cells transfected with the corresponding plasmids suggested that
      distinct regions at the termini of DI RNA are important for RNA replication.
      Region I, encompassing nucleotides 1-24, is absolutely required for replication
      since DI RNA genomes lacking any part of this region failed to replicate. Region
      II, spanning nucleotides 25-45, is not essential for replication but it functions
      as an enhancer of replication in that the presence of these specific sequences
      confers high efficiency of replication to the template. Deleting these specific
      sequences from both termini of DI RNA but maintaining the length of terminal
      complementarity as seen in wild-type DI RNA resulted in a template that
      replicated poorly (about 20-fold less efficiently). Furthermore, insertion or
      substitution of these sequences into the 3'-terminus of a VSV minigenome resulted
      in a template that replicated more efficiently (at least 4-fold to as high as 15
      fold) than the parental minigenome. These results strongly support the conclusion
      that the presence of specific sequences rather than the extent of complementarity
      at the termini of DI RNA is a major determinant of the efficiency of replication.
      The presence of the specific sequences at the 3'-terminus of both genomic and
      antigenomic DI RNAs may explain in part the replicative dominance of DI RNA over
      the full-length VSV genome which contains these sequences only at the 3'-terminus
      of the antigenome.

PMID- 9191839
TI  - The assembly of the measles virus nucleoprotein into nucleocapsid-like particles
      is modulated by the phosphoprotein.
AB  - Measles virus nucleoprotein encoded from the vaccinia virus genome assembles into
      nucleocapsids similar in many respects to those observed during a natural measles
      virus infection. The influence of the measles virus phosphoprotein on
      nucleocapsid assembly has been studied using a vaccinia virus recombinant
      encoding both the nucleoprotein and the phosphoprotein. Infection of cells with
      the virus recombinant resulted in the formation of cytoplasmic inclusions in
      which the nucleoprotein and the phosphoprotein colocalized. Electron microscopic
      examination suggested that these inclusions contained characteristic nucleocapsid
      filaments. The buoyant density of nucleocapsids assembled in the presence of the
      phosphoprotein was found to be slightly higher than that of nucleocapsids
      assembled in its absence. Furthermore, the phosphoprotein partially inhibited the
      formation of nucleocapsids, a process which was extremely efficient when the
      nucleoprotein was expressed alone. Analysis of the nucleic acid content of
      nucleocapsids showed that they packaged heterologous RNA into a micrococcal
      nuclease-resistant form. These experiments demonstrate that the measles virus
      phosphoprotein regulates the efficiency with which the nucleoprotein assembles
      into nucleocapsids and the structural conformation they acquire.

PMID- 9191840
TI  - Regulation of a geminivirus coat protein promoter by AL2 protein (TrAP): evidence
      for activation and derepression mechanisms.
AB  - Tomato golden mosaic virus (TGMV) is a bipartite member of the subgroup III
      Geminiviridae. Like all geminiviruses, TGMV replicates in the nucleus of
      susceptible cells by rolling circle replication (RCR). Double-stranded
      replicative form DNA generated during RCR serves as template for the
      transcription of viral genes by RNA polymerase II and the associated cellular
      transcription machinery. Previous studies in tobacco protoplasts and Nicotiana
      benthamiana leaf discs have shown that the viral AL2 gene product transactivates
      expression of the coat protein (CP) and BR1 movement protein genes, and that
      activation occurs at the level of transcription. Because of its function and
      properties, we propose the name TrAP, transcriptional activator protein, for the
      AL2 gene product. Using transgenes consisting of complete and truncated versions
      of the CP promoter fused to the GUS reporter gene, we show in the studies
      presented here that TrAP is required for CP gene expression in both mesophyll and
      phloem tissues. Surprisingly, TrAP appears to induce CP expression by different
      mechanisms in different cell types: it may activate the CP promoter in mesophyll
      cells, and acts to derepress the promoter in phloem tissue. In addition, TrAP is
      clearly capable of inducing the expression of responsive chromosomal promoters
      and could, in principle, activate host genes. Distinct viral sequence elements
      mediate expression and derepression in phloem and activation in mesophyll,
      suggesting that TrAP interacts with different components of the cellular
      transcription machinery to accomplish CP gene expression in different cell types,
      and underscoring the intricacy and complexity of virus-host interactions.

PMID- 9191841
TI  - Changes in the dengue virus major envelope protein on passaging and their
      localization on the three-dimensional structure of the protein.
AB  - To help define the molecular events involved in dengue virus adaptation during
      serial passage in vivo and in cultured cells, we have sequenced the structural
      protein genes of three dengue type 3 isolates after intracerebral passage in mice
      and after passage in cultured monkey kidney (Vero) and Aedes albopictus
      (mosquito) cells. Passaging in each host selected for amino acid changes in the
      envelope protein E and occasionally in prM but not in the capsid protein. Most
      changes were first apparent within five passages. Nineteen of twenty mutations in
      the structural protein genes resulted in amino acid changes concentrated on 12
      residues; 9 of the 12 amino acid changes were at residues which are conserved
      between the four dengue virus serotypes. Certain amino acid changes were
      repeatedly selected on passage in cell culture. In six independent Vero cell
      passage series, changes were observed in E at residues 191 (four times), 202
      (twice), 266 and 268 (three times), and 291; change in prM was seen in two
      passage series at residue 26. Two independent passage series in mosquito cells
      each resulted in the loss of a conserved glycosylation site at Asn 153 in E.
      Passage in mouse brain selected for mutations at E residues 18, 54, 277, 401, and
      403. Residues which altered on passaging have been localized on the three
      dimensional structure of the tick-borne encephalitis virus E protein soluble
      fragment (F. A. Rey, et al., 1995, Nature 375, 291-298). Residues 54, 191, 202,
      266, 268, and 277 map to a postulated "hinge" region between domains I and II
      which may be involved in fusion of flaviviruses with cell membranes. The
      oligosaccharide at Asn 153 also appears to be involved in flavivirus fusion.
      Changes in the fusion characteristics of the passaged viruses were demonstrated.

PMID- 9191842
TI  - Replacement of posttranscriptional regulation in SIVmac239 generated a Rev
      independent infectious virus able to propagate in rhesus peripheral blood
      mononuclear cells.
AB  - Lentiviruses control virion production via posttranscriptional regulation
      mediated by the viral Rev protein. In this study, we demonstrate that the Rev
      regulation of SIVmac239 can be replaced by the presence of the cis-acting
      transport element (CTE) of the type D simian retroviruses 1 (SRV-1). To avoid the
      possibility of generating revertants, the Rev-Independent SIV clones have both
      rev and the Rev responsive element (RRE) destroyed by multiple point mutations
      that do not affect the overlapping tat and env open reading frames. Virus stocks
      generated from these Rev-independent SIV molecular clones can infect and can be
      propagated in rhesus peripheral blood mononuclear cells (PBMCs). Therefore, the
      Rev/RRE system of SIVmac239 can be replaced by the SRV-1 CTE as previously shown
      for HIV-1. In both rhesus and human primary cells, the replicative capacity of
      the Rev-independent SIV is 10- to 20-fold lower than that of the wild-type virus.
      Rhesus PBMC-derived virus stocks of the Rev-independent SIV have lower
      infectivity. Interestingly, in CEM x 174 cells, no difference in replicative
      capacity between wild-type and Rev-independent SIV has been observed. The Rev
      independent SIV has a stable genotype after several passages in primary cells.
      The availability of such Rev-Independent viruses will allow the study of the role
      of Rev in pathogenesis and the potential generation of attenuated SIV strains.

PMID- 9191843
TI  - DNA replication promotes high-frequency homologous recombination during
      Autographa californica multiple nuclear polyhedrosis virus infection.
AB  - The relative ease with which foreign genes can be incorporated into the genome of
      the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV)
      indicates that a highly efficient recombinational process exists within infected
      cells. However, it is unclear whether this is due to marker transfer mediated by
      host cell enzymes or recombination events promoted by AcMNPV itself. To address
      the latter possibility, a pair of inverted repeat IS50 elements derived from the
      bacterial transposon Tn5 was inserted into the polyhedrin gene locus of the
      AcMNPV genome. Inversion of Tn5 sequences arising from recombination between its
      IS50 repeats could be readily detected in this virus, indicating that AcMNPV DNA
      undergoes high-frequency recombination during infection. To further characterize
      this process, a transient recombination assay was developed and used to identify
      the cis- and trans-acting requirements for Tn5 inversion in AcMNPV. A transfected
      Tn5-containing plasmid was found to undergo the same sequence inversion events
      seen in the viral genome, but only if it also contained a putative AcMNPV origin
      of replication (homologous region 2) in cis and was replicated by AcMNPV gene
      products supplied in trans. Taken together, these results indicated that
      recombination events which occur in infected cells were strictly dependent upon
      AcMNPV-mediated DNA replication. Direct support for this hypothesis was provided
      by the observation that the minimal set of AcMNPV genes that was essential for
      plasmid DNA replication also promoted recombination events leading to Tn5
      inversion in the absence of any other viral function. Finally, using a panel of
      deletion mutants of the IS50 elements in Tn5, sequence inversion was shown to be
      the result of homologous rather than site-specific recombination, since it
      occurred independently of a discrete sequence within the transposon. These
      results demonstrate that the AcMNPV DNA replication machinery exhibits a strong
      propensity to promote homologous recombination events during infection and is
      likely to play a role in the high frequency of marker transfer observed in this
      virus.

PMID- 9191844
TI  - Continued evolution of H1N1 and H3N2 influenza viruses in pigs in Italy.
AB  - Swine influenza viruses possessing avian genes were first detected in Europe in
      1979 (Scholtissek et al., 1983, Virology, 129, 521-523) and continue to circulate
      in pigs in that region of the world. To characterize the molecular epidemiology
      of swine influenza viruses currently circulating in Europe, we used dot-blot
      hybridization and sequence analysis to determine the origin of the genes encoding
      the nonsurface proteins ("internal" genes) of 10 H1N1 and 11 H3N2 swine influenza
      viruses isolated in Italy between 1992 and 1995. All of the 126 genes examined
      were of avian origin; thus the currently circulating H3N2 strains which possess
      A/Port Chalmers/1/73-like surface glycoproteins appear to be descendants of the
      reassortant human-avian viruses that emerged between 1983 and 1985 in Italy.
      Sequence analysis of matrix (M), nonstructural, and nucleoprotein genes, as well
      as phylogenetic analysis of M gene showed that the H1N1 and H3N2 viruses from the
      pigs were closely related to recent isolates of the avian-like swine H1N1
      influenza strain currently circulating in northern Europe and were
      distinguishable from the genes of viruses isolated from European swine in 1979.
      To evaluate the frequency of transmission of swine H1N1 and H3N2 viruses to man,
      we tested 123 human sera for hemagglutination-inhibiting antibodies against avian
      and mammalian H1N1 and H3N2 virus strains. Our findings indicate that swine
      influenza viruses possessing A/Port Chalmers/1/73-like hemagglutinin may have
      transmitted to approximately 20% of young persons under 20 years of age who had
      contact with pigs. Thus, H3N2 swine viruses, possibly possessing avian-derived
      internal genes, may be entering humans more often than was previously thought. We
      strongly recommend that pigs be regularly monitored as a potential early warning
      system for detection of future pandemic strains.

PMID- 9191845
TI  - Activity of human immunodeficiency virus type 1 promoter/TAR regions and tat1
      genes derived from individuals with different rates of disease progression.
AB  - Different rates of disease progression may be associated with different human
      immunodeficiency virus type 1 (HIV-1) promoter and/or transactivator activities.
      We therefore analyzed the sequences and activities of the first exon of Tat,
      tat1, and the promoter/trans-acting responsive (TAR) regions amplified directly
      from peripheral blood mononuclear cells obtained from five long-term
      nonprogressors and eight progressing HIV-1-infected individuals. The majority of
      tat1 alleles and promoter/TAR regions from all patients were intact and showed
      comparable activities in transient reporter assays. A substantial number of point
      mutations and some length variations were observed in the promoter/TAR region. In
      a single nonprogressor, the Sp1 binding site 3 was consistently altered and the
      transcriptional activity in the presence of Tat was diminished. Some LTR clones
      from a rapid progressor contained a fourth Sp1 binding site, which was associated
      with an elevated basal promoter activity. These data suggest that defects in the
      promoter/TAR region or tat1 are rare and that different promoter/transactivator
      activities are not commonly associated with different progression rates.

PMID- 9191846
TI  - Phosphorylation of the adeno-associated virus replication proteins.
AB  - The adeno-associated virus (AAV) replication proteins Rep78 and Rep68 regulate
      viral gene expression and DNA amplification. Their effects on both processes
      suggest that they play roles in all phases of the virus life cycle. We have
      investigated Rep protein phosphorylation to determine if this modification might
      alter Rep function. All four Rep proteins were found to be phosphorylated in AAV
      and adenovirus co-infected cell cultures, and Rep proteins contained phospho
      serine whereas no phospho-threonine or -tyrosine was detected. We also observed
      that when viral DNA synthesis was inhibited, there was a significant decrease in
      the level of Rep78/68 phosphorylation. Our results suggest a plausible mechanism
      whereby AAV Rep 78/68 function may be regulated by phosphorylation.

PMID- 9191847
TI  - The long terminal repeats of human immunodeficiency virus type-1 and human T-cell
      leukemia virus type-I are activated by 12-O-tetradecanoylphorbol-13-acetate
      through different pathways.
AB  - The LTRs of HIV-1 and HTLV-I have been shown by several laboratories to be
      activated by 12-O-tetradecanoylphorbol-13-acetate (TPA). This agent is a potent
      activator of protein kinase C (PKC). However, long exposure to TPA downregulates
      PKC in many cell types. We demonstrated that TPA treatment of Jurkat cells for
      more than 24 hr resulted in a sever depletion of this enzyme. Therefore, to
      explore the role of PKC in the effect of TPA on these LTRs, we transfected Jurkat
      cells with HIV-1 LTR-CAT or HTLV-I LTR-CAT construct after 72 hr of TPA
      pretreatment. While this TPA pretreatment considerably reduced the HIV-1 LTR
      basal expression, it strongly stimulated the expression of HTLV-I LTR.
      Furthermore, when TPA was added after transfection, a strong stimulation of HIV-1
      LTR was observed, which could be abrogated by PKC inhibitors like H7 and
      chelerythryn. However, under these conditions TPA stimulated HTLV-I LTR to a
      lesser extent than did the long-term TPA pretreatment. Moreover, this stimulation
      was enhanced by the PKC inhibitors. Thus our data indicate that while the effect
      of TPA on HIV-1 LTR is strictly dependent on PKC activity, its effect on HTLV-I
      LTR is exerted via a different pathway that not only does not require PKC
      activation but rather seems to be antagonized by the activated PKC. Using a
      deletion mutant of HTLV-I LTR we mapped the PKC-independent effect of TPA to the
      c-ets responsive region 1 (ERR-1) located in U3 of this LTR.

PMID- 9191848
TI  - Specification of receptor-binding phenotypes of influenza virus isolates from
      different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and
      H3 influenza A and influenza B viruses share a common high binding affinity for
      6'-sialyl(N-acetyllactosamine).
AB  - Synthetic sialylglycoconjugates bearing 3'-sialyllactose, 6'-sialyllactose, or 6'
      sialyl(N-acetyllactosamine) moieties attached to the polyacrylic acid carrier (P
      3-SL, P-6-SL, and P-6-SLN, respectively) were prepared and tested for their
      ability to bind to influenza virus isolates from different hosts in a competitive
      solid phase assay. The virus panel included egg-grown avian and porcine strains,
      as well as human viruses isolated and propagated solely in mammalian (MDCK) cells
      and their egg-adapted variants. A clear correlation was observed between the
      pattern of virus binding of two glycopolymers, P-3-SL and P-6-SLN, and the host
      species from which the virus was derived. Avian isolates displayed a high binding
      affinity for P-3-SL and a two to three orders of magnitude lower affinity for P-6
      SLN. By contrast, all non-egg-adapted human A and B viruses bound P-6-SLN
      strongly but did not bind P-3-SL. Unlike the "authentic" human strains, their egg
      adapted counterparts acquired an ability to bind P-3-SL, indicative of a shift in
      the receptor-binding phenotype toward the recognition of Neu5Ac2-3Gal-terminated
      sugar sequences. Among the porcine viruses and human isolates with porcine
      hemagglutinin, few displayed an avian-like binding phenotype, while others
      differed from both avian and human strains by a reduced ability to discriminate
      between P-3-SL and P-6-SLN. Our data show that sialylglycopolymers may become a
      useful tool in studies on molecular mechanisms of interspecies transfer, tissue
      specificity, and other structure-function relationships of the influenza virus
      hemagglutinin.

PMID- 9191849
TI  - Bovine herpesvirus 1-induced apoptosis occurs at the G0/G1 phase of the cell
      cycle.
AB  - We have previously shown that bovine herpesvirus 1 (BHV-1), even when
      inactivated, induces apoptotic cell death in mitogen-stimulated bovine peripheral
      blood mononuclear cells (PBMCs) (Hanon et al., 1996, J. Virol. 70, 4116-4120). In
      order to gain insight into this process, we have investigated the cell cycle
      phase at which BHV-1 induces apoptosis in PBMCs. Our results show that the
      percentage of cells that progress through the S phase was always lower in BHV-1
      infected PBMCs than in control cells. This effect was not due to a defective
      activation of mitogen-stimulated PBMCs since BHV-1 only slightly affected the
      percentage of cells expressing BoCD25, a well-known lymphocyte activation marker.
      Furthermore, mimosine and cyclosporine A, two chemicals that inhibit entry into
      the S phase of the cell cycle by different pathways, did not affect the ability
      of BHV-1 to induce apoptosis. BHV-1-induced apoptosis also occurred in
      unstimulated PBMCs and interestingly, this was associated with the expression of
      c-myc and BoCD25 proteins both of which are related to cell cycle progression.
      All together, these data provide evidence demonstrating that BHV-1-induced
      apoptosis occurs at the G0/G1 phase of the cell cycle.

PMID- 9191850
TI  - The N-terminal portion of the 216-kDa polyprotein of Commelina yellow mottle
      badnavirus is required for virus movement but not for replication.
AB  - Commelina yellow mottle virus (CoYMV) is the type member of the badnaviruses, a
      genus of plant pararetroviruses. The N-terminus of the polyprotein encoded by ORF
      III has limited similarity to known cell-to-cell movement proteins. To test the
      hypothesis that the N-terminus is required for viral movement, the phenotypes
      caused by mutations constructed in this region were determined. Similar to
      mutants affected in the reverse transcriptase, mutants affected in the putative
      movement protein were unable to cause a systemic infection. However, when the
      abilities of the mutated viral genomes to direct virion assembly and replication
      were tested using an in vitro stem-culture system, the mutants affected in the
      putative movement protein were found to assemble virions, whereas the reverse
      transcriptase mutants were unable to do so. Moreover, the putative movement
      protein mutants were shown to be replication competent by detection and mapping
      of one of the genomic discontinuities that are the hallmark of replication by
      reverse transcription. Thus the N-terminal region of ORF III is required for the
      systemic movement but not for the replication of CoYMV.

PMID- 9191851
TI  - Transcriptional induction of multiple cytokines by human respiratory syncytial
      virus requires activation of NF-kappa B and is inhibited by sodium salicylate and
      aspirin.
AB  - Infection of the lung epithelial cell line A549 by respiratory syncytial virus
      (RSV) resulted in the elevated synthesis of multiple cellular cytokines,
      including a number of interleukins (ILs). Detailed studies of IL-11 induction
      revealed that it required infection by viable virus and involved a net increase
      in the steady state level of IL-11 mRNA. Nuclear run-on assays showed a direct
      effect of RSV on IL-11 gene transcription. Mutational analysis of the IL-11
      promoter fused to a reporter luciferase gene demonstrated the requirement of a
      region 720 nucleotides upstream of the mRNA start site in the transcriptional
      induction of IL-11 by RSV. Two nearly identical 10-nucleotide-long sequences
      GGGGTCTCCC and GGGTCTCCCC in this region resembled the NF-kappa B consensus
      motif. Mutation of either sequence greatly reduced RSV-mediated induction of IL
      11 promoter activity. NF-kappa B sites in IL-1 alpha, IL-6, and IL-8 promoters
      were also required for RSV-mediated induction of transcription of these
      promoters. Immunological studies and use of reporter gene constructs provided
      direct evidence for the activation and nuclear translocation of NF-kappa B by
      RSV. Sodium salicylate and aspirin, inhibitors of NF-kappa B activation,
      abolished transcriptional induction of all these cytokines by RSV. Together,
      these studies demonstrated an essential role of NF-kappa B in RSV-mediated
      transcription of multiple cytokines genes and suggested a possible use of
      salicylates in managing airway inflammation and viral pathogenesis during RSV
      infection.

PMID- 9191852
TI  - Cell proliferation is not required for productive HIV-1 infection of macrophages.
AB  - Lentiviruses, including HIV-1, are considered a rare example of retroviruses
      which do not require cell proliferation for their replication. However, this
      notion was questioned in several publications where productive HIV-1 infection
      was found to be restricted to a small fraction of macrophages with proliferative
      capacity. Since the mode of HIV-1 replication in macrophages is of great clinical
      relevance, we performed a single-cell analysis of HIV-1 replication and
      [3H]thymidine incorporation. Our results indicate that while 17% macrophages were
      detected as HIV-1 DNA-positive 12 hr after infection, only 2% of those cells had
      incorporated tritium, about the same percentage as in the uninfected cell
      population. Forty-eight hours after infection, 38% macrophages were HIV-1 DNA
      positive and 47% of those had incorporated tritium, while the percentage of
      tritium-positive uninfected cells did not change (1%). These results demonstrate
      directly that HIV-1 DNA does not colocalize with [3H]thymidine and support the
      notion that cell proliferation is not required for HIV-1 infection of
      macrophages.

PMID- 9191853
TI  - Molecular studies on bromovirus capsid protein. III. Analysis of cell-to-cell
      movement competence of coat protein defective variants of cowpea chlorotic mottle
      virus.
AB  - To determine whether the role of coat protein (CP) in cell-to-cell movement of
      dicot-adapted cowpea chlorotic mottle bromovirus (CCMV) is distinct from that of
      monocot-adapted brome mosaic bromovirus (BMV), two reporter genes, beta
      glucuronidase (GUS) and enhanced green fluorescent protein (EGFP), were
      substituted for the CP in a biologically active clone of CCMV RNA3 (C3). Primary
      leaves of Nicotiana benthamiana, Chenopodium quinoa, and cowpea were co
      inoculated with wild-type (wt) CCMV RNA 1 and -2 and either C3/delta CP-GUS or
      C3/delta CP-EGFP and analyzed for GUS activity or the presence of green
      fluorescence. The visual appearance of infections caused by GUS or EGFP variants
      indicated that, in CCMV, epidermal cell-to-cell movement can occur without a
      functional CP. By contrast, inoculation of MP defective variants of C3/delta CP
      GUS or C3/delta CP-EGFP resulted in subliminal infections. Additional experiments
      examining the infectivity of wt BMV RNA 1 and -2 and a BMV RNA3 variant bearing
      the EGFP in the place of CP (B3/delta CP-EGFP) confirmed previous observations
      that, unlike CCMV, epidermal cell-to-cell movement of BMV is dependent on the
      expression of a functional CP. Taken together, the results demonstrate that BMV
      and CCMV use different mechanisms for initial epidermal cell-to-cell spread, and
      the individual role played by the respective CP genes in this active process is
      discussed.

PMID- 9191854
TI  - Lack of evidence for the transmission of JC polyomavirus between human
      populations.
AB  - Human polyomavirus JC virus (JCV), the causative agent of progressive multifocal
      leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically
      then persisting in renal tissue. Since JCV DNA can readily be detected from
      urine, it should be a useful tool with which to study the mode of virus
      transmission in humans. Based on this notion, we examined the extent to which JCV
      was transmitted from the American to Japanese populations in Okinawa Island,
      Japan. (A population of about 50 000 American soldiers and families have been
      stationed in Okinawa since 1945.) Four JCV types (A to D) were identified in
      American populations in U.S.A., whereas only type B was prevalent in elder
      Japanese in Okinawa who had reached adulthood by 1945. Thus, types A, C, and D
      served as indicators of the transmission of JCV from American to Japanese
      populations. We then examined whether types A, C, and D were detectable in
      Japanese in Okinawa aged 30-50 years who may have been in contact with Americans
      during childhood. However, all the 125 isolates from the younger Japanese
      population were type B without exception. From this finding, we concluded that
      JCV is rarely transmitted between human populations.

PMID- 9191855
TI  - The herpes simplex virus type 1 ribonucleotide reductase is required for acute
      retinal disease.
AB  - We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR)
      null mutant (ICP6 delta) to determine if the HSV-1 RR is required for acute
      retinal disease. Injection of the ICP6 delta mutant into the vitreous induced
      mild transient signs of infection (vitreal infiltrate, retinal inflammation, and
      changes in retinal cytology). In contrast, the parental KOS and a revertant virus
      (ICP6 delta + 3.1) in which the RR gene had been restored, caused severe
      retinitis. Injection of media alone also induced mild transient signs of disease.
      Two months after infection, ICP6 delta injected eyes could not be distinguished
      from normal eyes. Repeated injection of ICP6 delta (3 times, 2 weeks apart)
      resulted in vitreal infiltrate near the site of injection but the retina did not
      appear damaged. The mutant, ICP6 delta, grew to peak titers 1 x 10(3) to 1 x
      10(5)-fold lower and cleared faster than KOS or ICP6 delta + 3.1 in the injected
      eyes suggesting that the reduced virulence was due to reduced ability of the
      virus to grow. These results show that the viral RR is required for acute retinal
      disease.

PMID- 9191856
TI  - The dengue virus nonstructural-1 protein (NS1) generates antibodies to common
      epitopes on human blood clotting, integrin/adhesin proteins and binds to human
      endothelial cells: potential implications in haemorrhagic fever pathogenesis.
AB  - Antibody responses generated by mice to the dengue-2 virus NS1 protein (D-2V NS1)
      were influenced by MHC class II (I-A) haplotype but each antiserum cross-reacted
      with human fibrinogen, thrombocytes and endothelial cells. To investigate these
      findings, a highly avid subclone (MAb 1G5.4-A1-C3) was selected from a parent
      hybridoma that secreted a monoclonal antibody (MAb) specific for the native
      dimeric form of D-2V NS1. When MAb reactions were compared using a panel of
      overlapping synthetic peptides covering the entire protein sequence, dimer
      specificity was found to be a weak reaction with multiple ELK-type motifs present
      in either the positive (E/D-hydrophobic-K/R) or negative (K/R-hydrophobic-D/E)
      orientations. MAb 1G5.4-A1-C3 and highly avid anti-NS1 polyclonal antisera
      reacted with the NS1 proteins of the four dengue virus serotypes, but only weakly
      reacted with the NS1 proteins of the other flaviviruses. MAb 1G5.4-A1-C3 and
      several other anti-NS1 MAbs produced haemorrhage in mice, cross-reacted with
      human fibrinogen, thrombocytes and endothelial cells, with known epitopes or
      active sites on human clotting factors and integrin/adhesin proteins present on
      these cells. D-2V NS1 bound to human endothelial cells via a site within its N
      terminal region, which led to significantly increased binding of avid anti-NS1
      antibodies. These results identified a potential role of both 'antigenic' and
      'biochemical' mimicry in dengue haemorrhagic fever pathogenesis, consistent with
      clinical data.

PMID- 9191857
TI  - Distribution and relevance of equine herpesvirus type 2 (EHV-2) infections.
AB  - Equine herpesvirus type 2 (EHV-2) is a slow-growing, cytopathogenic
      gammaherpesvirus, which is suggested to be ubiquitous in the equine population.
      However, its precise role as a pathogen and its tissue tropism remains uncertain.
      To estimate the prevalence of EHV-2 in Germany and to investigate the possible
      pathogenicity of the virus, peripheral blood leucocytes (PBL) from 172 horses
      were examined for EHV-2 DNA by a sensitive and specific nested PCR based on the
      EcoRI-N genomic fragment and by classical cocultivation. PBL samples from 51% of
      the horses were positive by PCR and virus was isolated from 31% of the horses by
      cocultivation. However, almost all animals were seropositive for EHV-2. This may
      indicate that PBL do not harbour EHV-2 indefinitely after infection. Furthermore,
      a correlation between clinical signs and EHV-2 as a causative agent could not be
      determined. Nevertheless, the prevalence of virus was high among horses with
      upper respiratory tract disease, abortion and severe ataxia. The products of the
      second round of the PCR reactions showed size polymorphism. Sequencing of the
      products revealed that these size differences were due to repetition of the motif
      (AGACAGGGGCCATGCTGGC) between 9-16 times depending on the isolate, suggesting
      that the nested PCR might be a useful tool for the differentiation of EHV-2
      isolates.

PMID- 9191858
TI  - Establishment of serial persistent infections with bovine viral diarrhoea virus
      in cattle and sheep and changes in epitope expression related to host species.
AB  - A pestivirus was transmitted by contact from a persistently infected (P.I.)
      bullock to pregnant sheep. This resulted in the birth of P.I. lambs, one of which
      in turn was able to transmit virus by contact to pregnant cattle. Two of these
      animals gave birth to P.I. calves, from one of which the virus was again
      transmitted by contact with pregnant sheep, leading to another generation of P.I.
      lambs. The expression of one or more epitopes on the E2 glycoprotein of the
      viruses isolated from this series of alternate cattle-sheep transmissions
      appeared to depend on the host species. Thus, several monoclonal antibodies which
      bound strongly to, and neutralised, viruses isolated from the bovine hosts,
      failed to bind or neutralise in the case of sheep isolates. The viral consensus
      sequences of the E2 gene as well as parts of the 5' untranslated region and of
      the Npro and capsid genes were compared between the different isolates. This
      revealed a high degree of genetic stability. However, a single codon change at
      amino acid position 9 of the E2 gene correlated with and was able to cause the
      loss of particular epitopes.

PMID- 9191859
TI  - Involvement of dsRNA virus in the protein composition and growth kinetics of host
      Trichomonas vaginalis.
AB  - Trichomonas vaginalis harbors a double-stranded (ds)-RNA virus, and the presence
      of virus is related to upregulated expression and phenotypic variation of a
      prominent immunogen (Khoshnan A, Alderete JF (1994) J Virol 68: 4035-4038). To
      further test the influence of virus on T. vaginalis, virus-infected (V+) isolates
      were compared to virus-free (V-), agar-cloned progeny trichomonads derived from
      the parental isolates for accumulation of total proteins and cysteine
      proteinases. Comparative high resolution two dimensional (2D)-SDS-PAGE was
      performed of trichomonads grown in a chemostat under identical conditions. At
      least 47 proteins were identified as specifically expressed by representative V+
      isolate 347, and approximately 41 spots were specific to the corresponding V-
      progeny, showing an association between virus and the presence and absence of
      parasite proteins. Qualitatively and quantitatively dissimilar cysteine
      proteinase patterns were detected from numerous V+ isolates and the V- progeny. A
      2D analysis for isolate 347 showed the appearance of unique proteinase activities
      for parental parasites and presence of at least one proteinase in the V- progeny.
      Finally, the V+ T. vaginalis isolate 347, but not the V- isolate 347 progeny nor
      other V+ isolates, underwent fluctuations in density during chemostat growth
      allowing for purification of virus particles from the V+ isolate 347 supernatants
      during decreased parasite density.

PMID- 9191860
TI  - Bovine papillomavirus E5 oncogene stimulates DNA synthesis in C127 fibroblasts
      without general effects on growth factor responsive protein phosphorylations.
AB  - The bovine papillomavirus (BPV) transforming gene E5 is thought to modulate
      growth factor receptor function leading to a stimulation of growth factor signal
      transduction pathways. However, the influence of E5 on the range of receptor
      mediated changes in protein phosphorylation has not been addressed. We looked for
      the influence of E5 on DNA synthesis as well as the phosphorylation of over 1000
      cellular phosphoproteins in mouse C127 fibroblasts and subclones harboring wild
      type (ID13)-, E5- mutant (XL3-2), and E6- (E6oCl) mutant BPVs. The cells
      containing E5 had an altered growth response to fresh serum or PDGF but we
      observed no general influences of E5 transformation on sets of serum-, phorbol
      ester-, and PDGF-responsive phosphoproteins, comprising 25, 18, and 16
      overlapping members, respectively. Indeed, most of the phosphoproteins comprising
      these sets remain equally responsive to these growth factors in all four cell
      lines. The only evidence of an E5-specific influence on protein phosphorylation
      was with 4 phosphoproteins, two whose PDGF-responsiveness was abolished and two
      with abolished serum-, phorbol ester- and PDGF-responsiveness. Thus E5 modulates
      only a subset of the cascade of receptor-mediated downstream protein
      phosphorylations.

PMID- 9191861
TI  - Nucleotide sequence comparison of the segments S10 of the nine African
      horsesickness virus serotypes.
AB  - Segments 10 (S10) of the double-stranded RNA (ds RNA) genomes from African
      horsesickness virus (AHSV) serotypes 2, 4, 5, 6 and 7 were cloned and sequenced.
      Direct sequencing of previously reverse transcribed amplified (RT)-PCR segments
      S10 was also performed. Nucleotide sequences of two strains (the virulent
      Moroccan strain and a vaccine strain) of the same serotype (4) were determined.
      Sequences of the viral serotypes were analysed and compared to each other. Two in
      phase ATG codons were conserved in the S10 of AHSV-2, AHSV-4, AHSV-5, AHSV-6 and
      AHSV-7 and were considered candidate translation initiation codons of NS3 and
      NS3A respectively. A close relationship between serotypes 4, 5 and 9 and between
      serotypes 3 and 7 were described. Closer relationships of serotype 2 to the 1 and
      8 group on one hand and of serotype 6 to the 4, 5 and 9 group on the other hand
      were observed.

PMID- 9191862
TI  - Polymorphism of rabies viruses within the phosphoprotein and matrix protein
      genes.
AB  - Although the rabies virus P and M genes, encoding the viral phosphoprotein and
      matrix protein respectively, have been characterised for a few laboratory-adapted
      strains, there is essentially no information on the variability of these two
      genes in wild-type rabies viruses. In this study rabies viruses, responsible for
      epizootics in different wildlife species in three geographically distinct areas
      of North America, have been characterised at the P and M gene loci. These data
      reveal that the M gene and its encoded product are much more conserved than the P
      gene and its encoded phosphoprotein. The latter product harbors two variable
      domains which contribute to different hydropathy profiles for this protein for
      each of the rabies virus strains studied. Phylogenetic analysis of the nucleotide
      sequences generated in this study, together with data generated previously on the
      N and G genes of these rabies virus strains, indicated that similar evolutionary
      relationships are predicted regardless of the portion of the viral genome
      targeted.

PMID- 9191864
TI  - Analysis of canine herpesvirus gB, gC and gD expressed by a recombinant vaccinia
      virus.
AB  - The genes encoding the canine herpesvirus (CHV) glycoprotein B (gB), gC and gD
      homologues have been reported already. However, products of these genes have not
      been identified yet. Previously, we have identified three CHV glycoproteins, gp
      145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To
      determine which CHV glycoprotein corresponds to gB, gC or gD, the putative genes
      of gB, gC, and gD of CHV were inserted into the thymidine kinase gene of vaccinia
      virus LC16mO strain under the control of the early-late promoter for the vaccinia
      virus 7.5-kilodalton polypeptide. We demonstrated here that gp145/112, gp80 and
      gp47 were the translation products of the CHV gB, gC and gD genes, respectively.
      The antigenic authenticity of recombinant gB, gC and gD were confirmed by a panel
      of MAbs specific for each glycoprotein produced in CHV-infected cells.
      Immunization of mice with these recombinants produced high titers of neutralizing
      antibodies against CHV. These results suggest that recombinant vaccinia viruses
      expressing CHV gB, gC and gD may be useful to develop a vaccine to control CHV
      infection.

PMID- 9191863
TI  - Genetic variation and phylogenetic relationships of 22 porcine reproductive and
      respiratory syndrome virus (PRRSV) field strains based on sequence analysis of
      open reading frame 5.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) strains from 13
      states in the United States, Guatemala and Canada were used to compare the
      envelope glycoprotein gene (ORF 5) nucleotide and deduced amino acid sequences.
      The gene was the same size, 603 nt, for all the 22 field strains. These strains
      had 89-94% amino acid identity compared to reference strain VR 2332. A putative
      signal sequence and cleavage site between residues 31 and 32 was identified and
      three potential glycosylation sites were present on all but two strains.
      Hydrophobicity/hydrophilicity and surface probability analyses reveal a primary
      structure for the envelope glycoprotein (E protein) with six potential surface
      regions that could be antigenic sites. Similar E protein structural features are
      conserved for the prototype European PRRSV-Lelystad virus.

PMID- 9191865
TI  - Rabies viruses infect primary cultures of murine, feline, and human microglia and
      astrocytes.
AB  - Recent studies have reported the detection of rabies viral antigens and virions
      in astrocytes and microglia of rabies-infected animals. As a first step toward
      understanding whether these glial cells may be involved in rabies virus
      replication, persistence, and/or pathogenesis, we explored their potential to be
      infected in vitro. Primary cultures of murine, feline, and human microglia and
      astrocytes were infected with several different rabies viruses: two unpassaged
      street virus isolates, a cell culture-adapted strain, and a mouse brain-passaged
      strain. Infection, as determined by immunofluorescence, was detected in 15 of the
      16 (94%) virus-glial cell combinations. Replication of infectious virus,
      determined by infectivity assay, was detected in 7 of the 8 (88%) virus-cell
      combinations. These results show that astrocytes and microglia can be infected by
      rabies viruses, suggesting that they may have a potential role in disease,
      perhaps contributing to viral spread, persistence and/or neuronal dysfunction.

PMID- 9191866
TI  - New variant groups identified from HGV isolates.
AB  - We have determined the primary sequence of the 5' noncoding region (5' NCR) and
      putative helicase regions (NS-3) of hepatitis G virus (HGV) and GB virus C (GBV
      C) that were isolated in Japan from suspected cases of nonA-nonB and/or nonA-nonB
      nonC viral hepatitis by using RT-PCR, and we compared the newly isolated
      sequences with three established isolates. The addition of a "G" residue was
      found at the 5' terminus of all 8 Japanese isolates. These isolates were more
      clearly distinguished from the prototype viruses by comparison with the 5' NCR
      sequence than by comparison with the NS-3 region. Our results suggested that at
      least three distinct genomic variants of HGV exist. Genotyping of HGV by using RT
      PCR based on the sequence of the 5' NCR seems highly feasible.

PMID- 9191867
TI  - Conserved vRNA end sequences of Thogoto-orthomyxovirus suggest a new panhandle
      structure.
AB  - Panhandles are dsRNA structures formed by conserved sequences at the 5' and 3'
      ends of the influenza virus genomic RNA. They consist of two stems separated by a
      flexible bulge and serve as promoter for the viral polymerase. In the outer stem,
      melting of base pairs is a prerequisite for initiation of transcription. We
      compared the terminal sequences of Thogoto virus (THOV), a tick-borne
      orthomyxovirus, with those of influenza virus. Despite their overall similarity,
      the first U downstream of the 5' end of the panhandle (position 3 in influenza
      virus) is found at position 8 in the THOV sequence. This shift from position 3 to
      position 8 results in a radical change of the predicted secondary structure. In
      the outer stem, intra-strand base pairings are clearly favoured above inter
      strand hybridizations. As this secondary structure can explain the functioning of
      a mutant promoter of influenza virus with twice the activity of the wild-type, we
      propose a general validity of our "hook-like" panhandle structure.

PMID- 9191868
TI  - AZT blocks down-regulation of IL-2 and IFN-gamma gene expression in HIV acutely
      infected cells.
AB  - HIV infection causes dysregulation of cytokine gene expression in CD4+ T cells of
      the infected host. Azidothymidine (AZT) inhibits HIV replication by blocking
      reverse transcription. Using a one-stop cell-to-cell HIV infection model, we have
      investigated the expression of several key cytokines in HIV infected T cells in
      the absence or presence of AZT treatment. Acute HIV infection of T cells resulted
      in dramatic down regulation of the expression of IL-2 and INF-gamma mRNA. While
      beta-actin mRNA levels remained constant in both AZT-free and AZT treated
      cultures after HIV infection, it was found that AZT blocked the down regulation
      of IL-2 mRNA and INF-gamma mRNA in CD4+ T cells acutely infected with HIV.

PMID- 9191869
TI  - Genetic characterisation of an influenza A virus of unusual subtype (H1N7)
      isolated from pigs in England.
AB  - An H1N7 influenza A virus, isolated from pigs in England in 1992, was examined
      genetically to determine the characteristics and probable origin of the eight
      gene segments. Six of the RNA segments encoding PB2, PB1, PA, HA, NP and NS were
      related most closely to those of human viruses, whilst two of the RNA segments
      (NA and M) were related most closely to those of equine viruses. The HA gene was
      most similar to that of A/USSR/90/77 (H1N1) but amino acid differences suggested
      independent genetic drift. In contrast, there were relatively few changes in the
      NA and M genes compared to those of A/equine/Prague/1/56 (H7N7).

PMID- 9191870
TI  - Evidence for in vitro and in vivo autocatalytic processing of the primary
      translation product of beet necrotic yellow vein virus RNA 1 by a papain-like
      proteinase.
AB  - Beet necrotic yellow vein virus RNA 1 contains a single long ORF corresponding to
      the theoretical translation product of 237 kDa which contains the information
      necessary for replication of the viral genome. This ORF contains a putative
      papain-like proteinase domain which has been localized, on the basis of sequence
      alignments, between the helicase and polymerase domains. Here we show that the
      RNA 1 primary translation product can be cleaved autocatalytically in vitro into
      two species of 150 kDa and 66 kDa, the latter of which probably contains the
      entire polymerase domain. A 66 kDa protein was detected immunologically in
      infected C. quinoa protoplasts using an antiserum specific for the C-terminal
      region of the RNA 1 primary translation product, confirming that processing also
      occurs in vivo.

PMID- 9191871
TI  - Comparative amino acid sequence analysis of the outer capsid protein VP4 from
      four lapine rotavirus strains reveals identity with genotype P[14] human
      rotaviruses.
AB  - The genes encoding the outer capsid VP4 proteins of four lapine rotavirus
      strains, three isolated in the US (ALA, C-11 and BAP-2) and one isolated in Japan
      (R-2) were sequenced, and the predicted amino acid (aa) sequence was compared to
      all known rotavirus genotypes. A high degree of aa identity (96.8-98.9%) was
      found among the American lapine strains, while the Japanese rotavirus strain R-2
      shared less aa identity (89.5-90.0%) with the American strains. The four lapine
      rotaviruses shared the closest aa identity (90.6-94.9%) with the P[14] genotype,
      consisting of viruses isolated from humans in Italy, Finland and Thailand. These
      results indicate that the VP4 protein of the four lapine strains are genotype
      P14, and that among lapine strains there are possibly two subtypes, one
      represented by the American lapine strains and the other by the Japanese R-2
      strain.

PMID- 9191873
TI  - Phase IB trial of picibanil (OK-432) as an immunomodulator in patients with
      resected high-risk melanoma.
AB  - The microbial immunostimulant OK-432 has been studied intensively in preclinical
      systems and has shown promise as an anticancer agent in trials that have been
      conducted over the past 20 years in Japan. To date, no systematic dose response
      evaluation of this agent has defined its dose-limiting toxicity or
      immunobiological activity. A phase IA study has been conducted in 25 patients
      with metastatic cancer at the University of Pittsburgh Cancer Institute Melanoma
      Center, establishing 30 KE as the maximal tolerable dosage, on the basis of
      cutaneous reactions. Subsequently, 48 patients with resected high-risk melanoma
      participated in a phase IB study of OK-432. This study has evaluated the
      immunomodulatory activity of OK-432 at five dosages ranging from 1 KE to 20 KE,
      administered ID twice weekly for 3 months. A formal analysis of the treated
      population in comparison to the randomized control group has been conducted, and
      profound immunological effects have been defined in the group of patients treated
      with OK-432. Patients who participated in this trial had a significant depression
      of OK-432-inducible cytokine production (interleukin-1 beta, interferon gamma,
      and tumor necrosis factor alpha) at baseline. Treatment with OK-432 reversed this
      deficit for interferon gamma (IFN gamma) production in a dose-dependent manner,
      and mitigated the inhibition for interleukin-1 (IL-1) across all dosage groups.
      The impact of OK-432 upon other immunological functions of the treated cohorts is
      more variable, with durable suppression of mononuclear cell superoxide
      production, and in vitro cytotoxicity to tumor. Immunological characteristics of
      the entire cohort demonstrate a strong and significant correlation of elevated
      blood CD16+ cell counts and natural killer activity with early tumor progression
      and death due to melanoma. Favorable prognosis is associated with monocyte
      capacity to produce tumor necrosis factor (TNF), and polymorphonuclear leukocyte
      formylmethionyl-leucylphenylalanine-inducible superoxide release. This study
      reveals several new immunological correlates of tumor progression and lethal
      outcome in resected high-risk melanoma. It demonstrates that the depressed IL-1,
      TNF, and IFN gamma release associated with melanoma may be mitigated by treatment
      with OK-432. This study has defined treatment and dose response patterns of
      immunomodulation associated with one of the most complex immunological agents yet
      evaluated in phase IB trials, in a well-defined population of high-risk patients
      with resected melanoma.

PMID- 9191872
TI  - Toxicological and immunological evaluation of the MHC-non-restricted cytotoxic T
      cell line TALL-104.
AB  - The human MHC-non-restricted cytotoxic T cell line TALL-104 has been shown to
      display potent antitumor effects in several animal models with spontaneous and
      induced malignancies. In view of its potential future use in cancer therapy, we
      investigated the tolerability and target-organ toxicity of these cells in various
      animal species. The acute toxicity of TALL-104 cell administrations was evaluated
      in: (a) healthy immunocompetent mice and immunodeficient (SCID) mice bearing
      human tumors using multiple (up to 15) intraperitoneal (i.p.) injections, and (b)
      healthy dogs, tumor-bearing dogs, and healthy monkeys using multiple (up to 17)
      intravenous (i.v.) injections. TALL-104 cells were gamma-irradiated (40 Gy) prior
      to administration to mice and dogs, but administered without irradiation in
      monkeys. Cell doses ranged from 5 x 10(7)/kg to 10(10)/kg for each injection. All
      regimens were well tolerated, the main clinical signs observed being transient
      gastrointestinal effects. Moderate and transient increases in liver transaminase
      levels were observed in all animal species. Discrete and transient leukocytosis
      with neutrophilia was also noted in dogs and monkeys after i.v. injections of
      TALL-104 cells. Histological analysis revealed foci of hepatic necrosis with
      lympho-/mono-/granulocytic infiltration in immunocompetent mice injected i.p.
      with 5 x 10(9)-10(10) cells/kg. In the same mice, the colon showed an increased
      number of muciparous cells and alterations in the villi structure: these
      alterations were completely reversed by 72 h after the last injection, while
      liver alterations reversed more slowly (1 week). No delayed or chronic toxicity
      was observed in any of the animals even when non-irradiated TALL-104 cells were
      administered: both immunocompetent mice and healthy dogs were found to be grossly
      and histopathologically normal when sacrificed (1 year and 1 month after the last
      TALL-104 injection respectively). TALL-104 cells did not persist in these hosts.
      In addition, monkeys showed no molecular signs of TALL-104-cell-induced leukemia
      in their blood 1 year after the last cell injection. Despite immunosuppression,
      most of the tumor-bearing dogs as well as the healthy dogs and monkeys developed
      both humoral and cellular immune responses against TALL-104 cells. The data
      derived from these preclinical studies suggest that administration of high doses
      of irradiated TALL-104 cells is well tolerated and would be unlikely to induce
      severe toxicity if applied in clinical trials to the treatment of patients with
      refractory cancer.

PMID- 9191874
TI  - Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in
      mistletoe-treated cancer patients.
AB  - Mistletoe (Viscum album) extracts are widely used in adjuvant cancer therapy. We
      have investigated the in vitro responsiveness of T cells from mistletoe-treated
      cancer patients and untreated healthy donors to various preparations of mistletoe
      extracts. Proliferation of peripheral blood mononuclear cells from treated but
      not from untreated patients was observed in response to therapeutically used
      mistletoe extracts prepared from apple (mali) or pine (pini) host trees. The
      strongest proliferation was induced by a vesicle preparation of mali extract.
      Activation was strongly inhibited by interleukin-10. Using a newly developed flow
      cytometry assay, we determined that cell growth was restricted to CD4 T cells.
      Analysis with a panel of monoclonal antibodies against the variable region of the
      T cell receptor beta chain (V beta) revealed an oligoclonal pattern of CD4 T cell
      activation. These results indicate that therapeutic administration of mistletoe
      extracts sensitizes a restricted set of CD4 T lymphocytes in mistletoe-treated
      patients.

PMID- 9191875
TI  - Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal
      growth-factor receptor in patients with advanced malignant glioma.
AB  - Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF
      R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal
      antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed
      against EGF-R was produced for therapeutic use. Eight patients with primary or
      recurrent, EGF-R-positive glioblastomas entered the study, which was designed to
      evaluate the clinical effect of the mAb. In order to achieve a high tumor cell
      saturation, the mAb was injected intratumorally twice weekly through an
      implantable catheter. The total administered dose varied between 4 mg and 120 mg.
      In 3 patients with solid tumors, a massive tumor necrosis was noted, with
      infiltration of macrophages, granulocytes and T cells. A further 3 patients
      developed clinical and radiological signs of an intense, local, inflammatory
      reaction. There may be a relation between the mAb dosage and the antitumor
      effect, insofar as higher doses seemed to cause a more pronounced, inflammatory
      reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This
      anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable
      necrosis in glioblastoma. However, the planned schedule could not be completed,
      even after the dose level was re-adjusted, owing to inflammatory reactions, which
      were severe without prior tumor debulking.

PMID- 9191876
TI  - Role of macrophage-colony-stimulating factor in regulating the accumulation and
      phenotype of tumor-associated macrophages.
AB  - In order to better define the role played by tumor-cell-derived macrophage-colony
      stimulating factor (M-CSF) in regulating the recruitment and phenotype of tumor
      associated macrophages, Polyoma large T-transformed fibroblastoid cell lines,
      derived from M-CSF-deficient osteopetrotic op/op mice and their phenotypically
      normal op/+ littermate controls, were inoculated into SCID (severe combined
      immunodeficiency) recipients and both the proportion and phenotype of the
      macrophages present within the tumors generated were determined. The results
      obtained indicate that, although tumors derived from M-CSF-deficient and M-CSF
      producing tumor cell inoculate contain a similar proportion of macrophages, the
      macrophages isolated from tumors lacking M-CSF appear morphologically less mature
      and express lower levels of interleukin 1 beta, tumor necrosis factor alpha and
      FcR gamma II mRNA. Taken together, these data suggest that, although M-CSF does
      not appear to play a critical role in determining the macrophage content of these
      tumors, it does play a role in modulating the phenotype, and potentially the
      functional activity of the macrophages present within the tumor microenvironment.

PMID- 9191877
TI  - Postural effects on peritoneal transport and systemic uptake of radiolabeled
      monoclonal antibodies.
AB  - To optimize the regional delivery advantage with i.p. administration of
      monoclonal antibody (mAb) for radioimmunotherapy, it may be possible to delay the
      rate and extent of mAb absorption from the peritoneal cavity by simply altering
      the position of a patient after radioantibody administration. It has been shown
      that the hydrostatic pressure against the diaphragm plays a major role in the
      rate of egress of radioantibodies from the peritoneal cavity and that fluid
      removal from the peritoneal cavity can be altered by posture. The current study
      examined postural effects in normal rats following the i.p. injection of 125I
      5G6.4 murine IgG2a anticarcinoma antibody (45 microCi). A 10-ml injection volume
      of the radioantibody solution was administered to rats restrained in either a
      supine or inclined (reverse Trendelenburg; feet down at a 45 degrees angle)
      position. Pharmacokinetic analysis confirmed that the appearance of the
      radioantibody into the systemic circulation was delayed in the inclined group.
      The time to peak blood concentration was prolonged from 14.7 (supine) to 19.2
      (inclined) hours (P = 0.005). All other pharmacokinetic parameters were
      equivalent across the treatment groups. The mean half-life of 166 h, mean blood
      clearance of 9 ml/min, and mean steady-state volume of distribution of 36 ml were
      consistent with previous experience with this radioantibody in the rat. The
      intrinsic absorption profile indicated that the mean percentage absorption from
      the peritoneal cavity to the blood stream was greater in the supine animals from
      4 h after i.p. injection until absorption was complete. By 10 h after injection,
      absorption from the peritoneal cavity was essentially complete in the supine
      dosed animals, while those restrained in an inclined position had cleared only
      50% of the total absorbed dose. Hence, the regional delivery advantage afforded
      by intraperitoneal administration of the radioantibody may be further exploited
      by maintaining an inclined position throughout the absorption phase, a strategy
      that may be applicable to radioimmunotherapy of patients.

PMID- 9191878
TI  - Advantage of residualizing radiolabels for an internalizing antibody against the
      B-cell lymphoma antigen, CD22.
AB  - LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has
      a high sensitivity for detecting B-cell, non-Hodgkin's lymphoma (NHL), as well as
      an antitumor efficacy in therapeutic applications. The aim of this study was to
      determine whether intracellularly retained radiolabels have an advantage in the
      diagnosis and therapy of lymphoma with LL2. In vitro studies showed that
      iodinated LL2 is intracellularly catabolized, with a rapid release of the
      radioiodine from the cell. In contrast, residualizing radiolabels, such as
      radioactive metals, are retained intracellularly for substantially longer. In
      vivo studies were performed using LL2-labeled with radioiodine by a non
      residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine,
      DLT), or with a radioactive metal (111In). The biodistribution of a mixture of
      125I (non-residualizing chloramine-T compared to residualizing DLT), 111In
      labeled LL2 murine IgG2a or its fragments [F(ab')2, Fab'], as well as its
      humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell
      NHL cell line. Radiation doses were calculated from the biodistribution data
      according to the Medical International Radiation Dose scheme to assess the
      potential advantage for therapeutic applications. At all assay times, tumor
      uptake was higher with the residualizing labels (i.e., 111In and DLT-125I) than
      with the non-residualizing iodine label. For example, tumor/blood ratios of 111In
      labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing
      iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained
      for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ
      ratios also were higher with residualizing labels. No significant differences in
      tumor, blood and organ uptake were observed between murine and humanized LL2. The
      conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values
      comparable to those of iodinated LL2, the uptake of both antibodies being
      strongly dependent on tumor size. These data suggest that, with internalizing
      antibodies such as LL2, labeling with intracellularly retained isotopes has an
      advantage over released ones, which justifies further clinical trials with
      residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and 90Y
      labels for therapy.

PMID- 9191879
TI  - Protein tyrosine phosphatase roles in the regulation of lymphocyte signaling.
AB  - Tyrosine phosphorylation-based signaling cascades represent an integral component
      of the signaling circuitry connecting extracellular stimuli to cell response. As
      the molecular elements which drive such cascades have become increasingly well
      characterized, appreciation has grown for the critical roles played by protein
      tyrosine phosphatases (PTPs) in intracellular signal relay and for the capacity
      of PTPs to act not only as a counterbalance for protein kinase activities, but
      also as pivotal enzymes in directing and modulating signal relay and the
      translation of given stimuli to cell behaviour. PTP function has been
      particularly well studied in relation to lymphocyte antigen receptor signaling
      and the results of these studies have provided many novel and significant
      insights into the biochemical mechanisms whereby PTPs participate in the
      integration and interpretation of the complex transmembrane stimulatory signals
      driving cell function and development.

PMID- 9191880
TI  - The C1q-binding cell membrane proteins cC1q-R and gC1q-R are released from
      activated cells: subcellular distribution and immunochemical characterization.
AB  - Two types of widely coexpressed cell surface C1q-binding proteins (C1q-R): a 60
      kDa calreticulin-homolog which binds to the collagen-like "stalk" of C1q and a 33
      kDa protein with affinity for the globular "heads" of the molecule, have been
      described. In this report, we show that the two molecules are also secreted by
      Raji cells and peripheral blood lymphocytes and can be isolated in soluble form
      from serum-free culture supernatant by HPLC purification using a Mono-Q column.
      The two purified soluble proteins had immunochemical and physical characteristics
      similar to their membrane counterparts in that both bound to intact C1q and to
      their respective C1q ligands, cC1q and gC1q. In addition, N-terminal amino acid
      sequence analyses of the soluble cC1q-R and gC1q-R were found to be identical to
      the reported sequences of the respective membrane-isolated proteins. Ligand blot
      analyses using biotinylated membrane or soluble cC1q-R and gC1q-R showed that
      both bind to the denatured and nondenatured A-chain and moderately to the C-chain
      of C1q. Moreover, like their membrane counterparts, the soluble proteins were
      found to inhibit serum C1q hemolytic activity. Although cC1q-R was released when
      both peripheral blood lymphocytes and Raji cells were incubated in phosphate
      buffered saline for 1 hr under tissue culture conditions, gC1q-R was releasable
      only from Raji cells, suggesting that perhaps activation or transformation
      leading to immortalization is required for gC1q-R release. Subcellular
      fractionation of Raji cells and analyses by enzyme-linked immunosorbent assay and
      Western blotting showed that the two molecules are present in the cytosolic
      fractions as well as on the membrane. The data suggest that soluble forms of both
      C1q-binding molecules are released from cells and that these molecules may play
      important roles in vivo as regulators of complement activation.

PMID- 9191881
TI  - Vaccine-induced IgG antibodies to the linear epitope on the PorB outer membrane
      protein promote opsonophagocytosis of Neisseria meningitidis by human
      neutrophils.
AB  - The serotype 15 PorB protein of Neisseria meningitidis contains an N-terminal
      linear immunodominant B-cell epitope located on the putative loop 1 (VR1) region.
      This epitope has previously been shown to stimulate antibody formation in 74% of
      the vaccinees after three doses of the Norwegian group B outer-membrane vesicle
      (OMV) vaccine. In the present study, the purified PorB protein and the 23mer
      synthetic peptide D63b2 covering VR1 region were immobilized onto N
      hydroxysuccinimide-activated matrix and used for affinity purification of the
      specific IgG antibodies from sera of three selected vaccinees. PorB- and peptide
      D63b2-specific IgG preparations bound to the PorB protein on immunoblots and
      reacted with strain 44/76 and OMV complexes expressing the serotype 15 PorB
      protein, but not with the PorB-deficient mutant, suggesting high specificity for
      the PorB protein. Both PorB- and peptide D63b2-specific IgG were marginally
      bactericidal, but enabled strong opsonophagocytosis measured as respiratory burst
      response of human neutrophils and internalization of opsonized FTTC-labeled
      meningococci. The data indicate that about 30-57% of the bulk serum opsonic
      activity for the 44/76 bacteria could be ascribed to linear epitope-specific
      IgG1, thus contributing to vaccine-induced protection against systemic
      meningococcal disease via the opsonophagocytic route of pathogen clearance.

PMID- 9191882
TI  - Relationship of plasma HIV-RNA levels and levels of TNF-alpha and immune
      activation products in HIV infection.
AB  - The goal of this study was to determine the relationship between plasma human
      immunodeficiency virus (HIV) load and cytokine expression. HIV-RNA plasma levels
      were determined in 34 HIV-seropositive (HIV+) asymptomatic subjects [range: 0.5
      to 211 kiloequivalents (kEq)/ml HIV-RNAJ, by a modified branched-DNA (bDNA)
      assay. Plasma HIV-RNA levels were positively correlated with increased plasma
      levels of TNF-alpha, soluble TNF receptor type II, soluble IL-2 receptor, beta 2
      microglobulin, and neopterin, but not with plasma IL-6 levels. In contrast,
      increased viral load and diminished CD4 counts correlated weakly. TNF-alpha mRNA
      levels, as determined by bDNA technology, were not significantly increased in
      peripheral blood mononuclear cells (PBMC) isolated from HIV-infected subjects,
      compared to HIV-seronegative (HIV-) subjects, and were not correlated with plasma
      levels of HIV-RNA, cytokines, or activation markers. These results are consistent
      with the hypothesis that a self-reinforcing mechanism exists between TNF-alpha
      production and generalized immune activation on one hand with HIV replication on
      the other.

PMID- 9191883
TI  - Immunophenotyping of T lymphocytes by three-color flow cytometry in healthy
      newborns, children, and adults.
AB  - Reagents are now available which allow simultaneous assessment of three different
      fluorescence wave-lengths on most commercially available flow cytometers. Such
      three-color analyses provide more information than single- or dual-color
      analyses. The present study was undertaken in order to establish age-related
      differences in lymphocyte subpopulations by simultaneously measuring three
      surface antigens in newborns, children, and adults. A whole blood method was used
      to label cells with antibodies conjugated to FITC, PE, and perCP. We found that
      the percentage of lymphocytes expressing HLA-DR/CD28/CD8, HLA-DR/ CD38/CD8,
      CD95/CD45RO/CD8, CD95/CD45RO/CD4, CD95/CD4, and CD95/CD8 showed relative
      increases with age. The percentage of lymphocytes expressing CD28/CD8, CD38/CD8,
      and CD38/CD4 showed relative decreases with age, while the subset HLA-DR/CD38/
      CD4 did not change. Three-color flow cytometry is a powerful tool to more
      precisely define lymphocyte subsets than the current two-color methods. We
      present values using a three-color panel in healthy newborns, children, and
      adults.

PMID- 9191884
TI  - Quantitative analysis of leukocyte membrane antigen expression on human fetal and
      cord blood: normal values and changes during development.
AB  - We studied the antibody binding capacity (ABC) of various cell-surface antigens
      in normal human fetuses and term neonates on lymphocyte, monocyte, and
      polymorphonuclear (PMN) cells by quantitative flow cytometry also designated by
      quantimetry. Analysis of changes of expression level on these leukocytes during
      the developmental process was also investigated. The results indicated that the
      ABC values of most studied markers change during the maturational process. The
      ABC of lymphocyte-associated antigens studied such as CD5 and CD7 showed only a
      decrease from fetus to adult, whereas according to the type of molecule on
      monocyte and PMN there was either an increase or a decrease of ABC values
      dependent on the stage of the developmental process, from fetus to neonate or
      from neonate to adult. However, the ABC values of leukocyte membrane antigens
      such as CD16, CD46, and CD55 on all leukocytes and CD11b, CD11c, and CD35 on
      myeloid cells did not change. Their expression level was already mature in
      fetuses compared with adult cells. In addition, in this quantimetric approach,
      the analysis of the results for CD11a and CD8 suggested that the changes of CD11a
      expression level on lymphocyte subsets can depend on one mechanism, whereas there
      are probably at least two for CD8. Furthermore, the expression patterns of CD5,
      CD7, and CD11a change during maturation. We concluded that, even if the neonate
      response pattern to immunological challenge differs from an adult and this is
      based primarily on the relative numbers and functional activity of lymphocyte T
      subsets (especially TH1/TH2) and their cytokine profiles, these quantitative and
      qualitative phenotypical differences might also contribute to explain the
      functional peculiarities of leukocyte fetal and cord blood cells. All these
      findings support the notion of immaturity and maturity of ABC expression.

PMID- 9191885
TI  - Analysis of IgG subclasses of human antitopoisomerase I autoantibodies suggests
      chronic B cell stimulation.
AB  - Antitopoisomerase I autoantibodies are highly specific of scleroderma and are
      mainly IgG. The present study was designed to evaluate the prevalence of each IgG
      antitopoisomerase I subclass. An ELISA for the detection of IgG antitopoisomerase
      I subclasses was standardized and used to study the antibodies from 49
      antitopoisomerase I-positive patients identified from a total of 541 patients.
      Correlations and multivariate analysis were performed to determine the frequency
      of associations between the IgG antitopoisomerase I subclasses. All IgG
      antitopoisomerase I subclasses were found. Twelve patients (24.5%) had all four
      IgG antitopoisomerase I subclasses, 13 (26.5%) had three, 16 (32.7%) had two, and
      7 (14.3%) had only one antitopoisomerase I subclass. The presence of all four IgG
      antitopoisomerase I subclasses suggests that this specific B-cell is the target
      of multiple activation pathways which indicate that there is a complex T-cell
      cytokine-driven process. Together with the absence of other autoantibodies in
      these sera, our results support the concept of a multiple but highly selected and
      chronic B-cell activation in scleroderma patients with antitopoisomerase I.

PMID- 9191886
TI  - A primatized MAb to human CD4 causes receptor modulation, without marked
      reduction in CD4+ T cells in chimpanzees: in vitro and in vivo characterization
      of a MAb (IDEC-CE9.1) to human CD4.
AB  - A Primatized anti-CD4 monoclonal antibody (MAb), CE9.1, with V-domain from
      cynomolgus macaque (showing 92% homology with human consensus sequence V
      domains), and a human IgG1 constant region, was characterized in vitro and in
      vivo in chimpanzees. This MAb binds human CD4 with Kd of 1.0 nM and was also able
      to bind to human IgG Fc receptors (Fc gamma R). However, despite being of the
      IgG1 subclass, CE9.1 did not bind to complement component C1q, nor did it mediate
      complement-dependent cytotoxicity. Examination of T cells from a number of
      species showed restricted reactivity for CE9.1, recognizing only human and
      chimpanzee CD4. In both human and chimpanzee MLRs, it had an IC50 of about 10.0
      ng/mL. Therefore, a chimpanzee in vivo model was used to characterize CE9.1,
      CE9.1 caused transient decrease in the number of lymphocytes bearing the CD4
      receptor starting at doses of 0.3 mg/kg in an in vivo dose ranging study in one
      chimpanzee. This effect was reversed within approximately 7 days. In a multiple
      high-dose study in which 10.0 mg/kg of CE9.1 was administered at intervals of 1-3
      months, there was a dramatic loss of CD4 marker with a reciprocal increase in the
      number of CD3+ CD8- CD4- cells. The CD4 receptor was totally undetectable on
      these lymphocytes for 1-2 weeks, with a gradual, but complete, reversal within 4
      weeks. We interpret these observations as receptor modulation because, although
      there was apparent loss of CD4+ lymphocytes, an equivalent number of CD3+CD8- T
      lymphocytes were present in circulation in all four chimpanzees treated with 10.0
      mg/kg CE9.1. Even at this high dose, only limited reduction of CD4+ T lymphocytes
      was observed in these animals. These observations are in sharp contrast to what
      has been reported in rodents or in human clinical studies using other IgG1 mAbs
      to human CD4. CD8 counts, although variable, remained unaffected by CE9.1
      treatment. No adverse events were observed following administration of CE9.1 to
      chimpanzees, and there was no detectable host immune responses to the Primatized
      MAb.

PMID- 9191887
TI  - Cytokine dichotomy in peripheral nervous system influences the outcome of
      experimental allergic neuritis: dynamics of mRNA expression for IL-1 beta, IL-6,
      IL-10, IL-12, TNF-alpha, TNF-beta, and cytolysin.
AB  - Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease of
      the peripheral nervous system (PNS) that can be actively induced in Lewis rats by
      immunization with bovine PNS myelin and Freund's complete adjuvant. EAN is used
      as an animal model of the Guillain-Barre syndrome (GBS) in humans. To study the
      potential role of cytokines in EAN, we used in situ hybridization to detect mRNA
      expression of interleukin 1 beta (IL-1 beta), IL-6, IL-10, IL-12, tumor necrosis
      factor-alpha (TNF-alpha), TNF-beta, and cytolysin in sciatic nerve sections over
      the course of EAN. Cells expressing IL-1 beta and IL-6 mRNA appeared early and
      peaked on Day 7 postimmunization (p.i.), i.e., at onset of clinical signs of EAN,
      consistent with a role of these cytokine in an early immune response leading to
      autoaggressive immunity in EAN. TNF-alpha, TNF-beta, and IL-12 mRNA expression
      was maximally upmodulated on Day 14 p.i., i.e., at height of clinical EAN,
      favoring a role for these cytokines in disease development. On the contrary,
      transcription of cytolysin and IL-10 in sciatic nerves reached maxima during
      clinical improvement of EAN. The data argue for a major proinflammatory role for
      IL-1 beta, IL-6, TNF-alpha, TNF-beta, and IL-12 and a disease downregulating
      function for both cytolysin and IL-10 at the target site in EAN. These findings
      have relevance for future studies on pathogenesis and treatment of GBS in humans.

PMID- 9191888
TI  - Association of Sjogren's syndrome with hereditary angioneurotic edema: report of
      a case.
AB  - A case of hereditary angioneurotic edema (HANE) associated with Sjogren's
      syndrome is presented. One of the members of a pedigree of HANE due to deficiency
      of C1 inhibitor (C1INH) had a positive titer for anti-SS-A and anti-SS-B
      antibodies in the serum, complaining of symptom of dry eyes and dry mouth. A lip
      biopsy revealed lymphocytic infiltration of minor salivary glands. The patient
      had renal tubular acidosis (RTA). Thus the patient was diagnosed as suffering
      from Sjogren's syndrome with RTA.

PMID- 9191889
TI  - Uncoupling of T-cell antigen receptor and downstream protein tyrosine kinases in
      common variable immunodeficiency.
AB  - Patients with common variable immunodeficiency (CVID) are heterogeneous in the
      clinical manifestations of the disease and the underlying mechanisms leading to
      the immunodeficiency. Although the overt defect is an impairment in B-cell
      function, there is increasing evidence of primary T-cell dysfunctions in a
      proportion of patients with CVID. We have analyzed T-cells from six CVID patients
      for activation of both early and late events in response to TCR triggering. The
      data showed that T-cells from three of six CVID patients were defective in the
      capacity to initiate the TCR/CD3 signaling pathway by activating intracellular
      tyrosine kinases, associated with impaired proliferative responses to TCR/CD3
      triggering. Since both surface expression of the TCR/CD3 complex and
      intracellular expression of key tyrosine kinases such as p56lek and ZAP-70 were
      normal in these patients, our data suggest a defect in the earliest step of TCR
      signal transduction.

PMID- 9191891
TI  - Computational modelling of low-energy electron-induced DNA damage by early
      physical and chemical events.
AB  - Modelling and calculations are presented as a first step towards mechanistic
      interpretation and prediction of radiation effects based on the spectrum of
      initial DNA damage produced by low energy electrons (100 eV-4.5 keV) that can be
      compared with experimental information. Relative yields of single and clustered
      strand breaks are presented in terms of complexity and source of damage, either
      by direct energy deposition or by reaction of OH radicals, and dependence on the
      activation probability of OH radicals and the amount of energy required to give a
      single strand break (ssb). Data show that the majority of interactions in DNA do
      not lead to damage in the form of strand breaks and when they do occur, they are
      most frequently simple ssb. However, for double-strand breaks (dsb), a high
      proportion (approximately 30%) are of more complex forms, even without
      considering additional complexity from base damage. The greater contribution is
      from direct interactions in the DNA but reactions of OH radicals add
      substantially to this, both in terms of the total number of breaks and in
      increasing the complexity within a cluster. It has been shown that the lengths of
      damaged segments of DNA from individual electron tracks tend to be short,
      indicating that consequent deletion length (simply by loss of a fragment between
      nearby dsb) would be short, very seldom exceeding a few tens of base pairs.

PMID- 9191890
TI  - The molecular regulation of apoptosis and implications for radiation oncology.
AB  - One of the major goals of cancer research is to identify and understand the
      causes of cellular proliferation. The role of cell death, or lack thereof, in
      carcinogenesis, tumour growth, metastatic spread and response to treatment has
      been largely overlooked even though the morphology of apoptosis (programmed cell
      death) was clearly described over 20 years ago, and its importance in cancer
      speculated on at that time. Over the last 5 years, however, an explosion of
      research has focused on delineating the molecular components of the apoptotic
      pathways and examining the role of apoptosis in a tumour's growth and response to
      treatment. This review highlights the aspects of apoptosis most relevant to
      radiation oncologists and radiobiologists. The apoptotic pathways will be
      described, with attention to the stimuli that initiate apoptosis, the oncogenes
      and tumour suppressor genes that mediate apoptosis, and the effector enzymes
      (proteases and endonucleases) responsible for the execution of apoptosis. In
      addition, we review the effect of classically described radiobiology cell
      survival parameters-cell cycle stage, dose rate, linear energy transfer, oxygen,
      total dose, and fractionation-on radiation induced apoptosis.

PMID- 9191892
TI  - Calculation by microdosimetric methods of the formation by a single high-energy
      photon or electron of two lesions in the same DNA molecule.
AB  - The formation by a single high-energy photon or electron of two lesions (such as
      double-strand breaks) in the same DNA molecule is calculated by microdosimetric
      methods. The result is similar to a previous calculation using a target theory
      approach. Thus, it is reasonably certain that, for > or = 1 Gy of sparsely
      ionizing radiation acting on a DNA molecule of > or = 10(6) base pairs, < or = 3%
      of two-hit events such as deletions are from a single radiation event.

PMID- 9191893
TI  - Centric rings, acentric rings and excess acentric fragments based on a random
      walk interphase chromosome model.
AB  - Excess acentric fragments, consisting of acentric rings and acentric linear
      fragments, are among the most frequent kinds of chromosome-type aberrations
      produced by radiation. The frequency of acentric rings cannot be obtained
      directly by experiment but is estimated here from the ratio of acentric to
      centric rings, evaluated using a random-walk model for the organization of
      chromatin during interphase and an assumption that the probability of an exchange
      formation is proportional to the rate of collision between two DSB. This ratio is
      calculated to be 2.5 in low-LET irradiated human fibroblasts, significantly
      greater than the ratio if proximity effects are not considered. The calculated
      frequency of acentric rings is insufficient to account for all the observed
      excess acentric fragments. Assuming that the rest of the excess acentric
      fragments are due to incomplete exchanges, all possible recombinations between
      two DSB that result in acentric rings and acentric linear fragments have been
      identified. From the chromosome aberration data, the incompleteness parameter has
      been estimated. Intra-arm chromosome exchanges, either complete or incomplete,
      were estimated to account for more than 50% of the excess acentric fragments in
      human fibroblasts.

PMID- 9191894
TI  - Genetic factors influencing alpha-particle-induced chromosomal instability.
AB  - Alpha-particle-induced chromosomal instability in haemopoietic cells obtained
      from the CBA/H, DBA/2 and C57BL/6 inbred strains of mouse has been demonstrated
      at frequencies dependent on genotype. The CBA/H and DBA/2 strains may be regarded
      as 'sensitive' and the C57BL/6 strain as 'resistant'; resistance was dominant in
      cells from F1 hybrids. Previously, in cultures where we demonstrated radiation
      induced chromosomal instability we also demonstrated an enhanced and persisting
      oxyradical activity. Quantitative differences in superoxide generation have now
      been correlated with genetically determined differences in the expression of
      chromosomal instability. Our findings demonstrate an important influence of
      genetic factors in alpha-particle-induced chromosomal instability.

PMID- 9191895
TI  - Adenine-induced arrest of mammalian cells in early S-phase is related to the
      prevention of DNA synthesis inhibition caused by gamma-irradiation.
AB  - Adenine prevents the down-regulation of DNA synthesis in gamma-irradiated EAT and
      HL60 cells. This protective effect is related to the initiation of DNA
      replication. The effectiveness of this protection increases with the
      concentration of adenine in both cell lines. The maximum protective effect of
      adenine induced in EAT cells occurs at about 10 times lower concentration as
      compared with HL60 cells; however, the level of this effect is almost the same in
      both cell lines. The results indicate that the prevention of the down-regulation
      of DNA synthesis in gamma-irradiated EAT and HL60 cells is conditioned mainly by
      the arrest of the cells in the early S-phase. It is evident that DNA synthesis in
      cells beyond G1/S boundary is insensitive to gamma-radiation.

PMID- 9191896
TI  - Whole library-amplification and labelling of human chromosome-specific composite
      probes for fluorescence in situ hybridization (FISH) using PCR.
AB  - Chromosome painting with human-specific, whole-plasmid library probes has become
      a widespread technique in cytogenetic research and radiation biology. Fast and
      convenient methods for probe amplification and labelling are required that
      conserve the complexity of the libraries and stain the entire length of selected
      chromosomes. The present study uses PCR for amplification and labelling of the
      whole bluescribe plasmid libraries pBS1, pBS4 and pBS12 using M13 forward and
      reverse sequencing primer. Amplification and labelling can be accomplished within
      a few hours with a minimum of laboratory equipment and costs. It is therefore
      suitable for all laboratories that do not have the facilities for growing
      transformed bacteria containing plasmids with inserts of human origin.

PMID- 9191897
TI  - Heat-induced apoptosis and p53 in cultured mammalian cells.
AB  - Heat-induced apoptosis was studied in M10 and MOLT-4 cells by determining nuclear
      morphological changes, decrease in cell size, DNA degradation into fragments of
      about 30 kbp, and the appearance of internucleosomal DNA fragments (DNA ladders).
      Morphological changes in the nucleus were detected within 30 min after heat
      treatment at 44 degrees C in M10 cells, but much later (> 5 h) in MOLT-4 cells.
      In M10 cells, 30 kbp-DNA fragments were observed even at the end of the heat
      treatment and decreased 10 min later, while the DNA ladder increased at 10-30 min
      after heat treatment. DNA fragments of 30 kbp appeared in MOLT-4 cells at 1 h
      after the heat-treatment and apparently accumulated for up to 24 h. Heat
      treatment increased p53 protein in MOLT-4 cells but not in M10 cells. Analysis of
      the DNA sequence of the p53 gene revealed that M10 cells have a heterozygous
      mutation in codon 173 of exon 5. These results suggest that apoptosis is induced
      by hyperthermia in a cell-line dependent manner, that the formation of 30 kbp-DNA
      fragments is a very early event in apoptosis, that DNA fragmentation into a DNA
      ladder occurs via the 30 kbp fragments, and that apoptosis in heat-treated M10
      cells may be independent of p53.

PMID- 9191898
TI  - Quantifying the position and steepness of radiation dose-response curves.
AB  - Radiation dose-response curves are of fundamental importance both in practical
      radiotherapy and as the basis of more theoretical considerations concerning the
      potential benefit to be gained from modified dose-fractionation schedules or of
      the effects of dosimetric and biological variability. The steepness of the dose
      response curve is a key parameter and quantitative measures of steepness derived
      from clinical data are strongly needed. Unfortunately, there are many ambiguities
      associated with quantifying the steepness of radiation dose-response curves and
      these are identified and discussed in the present paper. The following problems
      are reviewed. (1) In the literature, various descriptors of 'steepness' are
      reported. We focus on the normalized dose-response gradient, gamma, and the dose
      response slope, theta. The mathematical properties and the relationship between
      these are discussed. (2) Steepness estimates depend on the mathematical model
      used to describe the dose response relationship. Three standard formulations are
      considered: the Poisson, the logistic and the probit dose-response model. The
      magnitude of the model dependence is influenced by the range of the empirical
      dose-response data available, and is most pronounced for data concentrated around
      very low or very high response levels. (3) Reparametrizations of the standard
      models in terms of position and steepness are given, and it is pointed out that
      some previously published formulas are only approximations. (4) The method of
      analysis can influence the steepness estimate. An analysis of a specific data set
      shows that the use of the least-squares method rather than the preferred maximum
      likelihood method may influence both the steepness estimate and its confidence
      interval. (5) Dose-response data generated with a fixed number of fractions
      rather than a fixed dose per fraction will produce steeper dose-response curves.
      The approximation involved in describing such a set of dose-response data by a
      position and a single steepness parameter is discussed. (6) The importance of
      specifying the statistical uncertainty of the steepness estimate is stressed. All
      of these problems are illustrated by a practical example, in which dose-response
      data from the literature are re-analysed.

PMID- 9191900
TI  - The damage to phospholipids caused by free radical attack on glycerol and
      sphingosine backbone.
AB  - The effect of gamma-radiation on aqueous solutions of saturated phospholipids,
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3
      phosphoglycerol (DPPG), 1-palmitoyl-2-lyso-sn-glycero-3-phosphocholine (lysoPC),
      and bovine brain sphingomyelin (SM) has been investigated. It is shown that the
      phospholipids with an OH group in beta-position to the P-O bond (DPPG and
      lysoPC), or to the amide bond (SM), undergo a free radical fragmentation. As a
      result of such fragmentation, stearoylamide, palmitoxyacetone and phosphatidic
      acid are formed from SM, lysoPC and DPPG, respectively. In parallel with the
      formation of hydrophobic fragments, an accumulation of hydrophilic species such
      as oxyacetone and phosphocholine in the irradiated DPPG and lysoPC dispersions
      was observed. On the basis of the data obtained for free radical transformation
      of phospholipids and their simplest analogs, such as glycero-1-phosphate,
      triacetin and 1,2-isopropylidene glycerol, it is suggested that the fragmentation
      of the radicals derived from the above compounds proceed by a concerted mechanism
      through a five-membered transition state. The accumulation of hydrophobic
      fragments in phospholipid membranes is shown to influence the temperature and co
      operativity of the 'gel-to-liquid crystal' phase transition. An assumption is
      made that the fragmentation of phospholipids caused by free radical attack on the
      hydrophilic moiety, along with lipid peroxidation, may constitute principal
      mechanisms of radiation-induced damage of biological membranes.

PMID- 9191899
TI  - Radiolysis of DNA in the presence of a protein studied by HPL-gel chromatography.
AB  - The influence of bovine serum albumin (BSA) on the radiolysis of double-stranded
      DNA was studied by measuring the loss of highly polymerized DNA with HPL-gel
      chromatography. The scavenger capacity of BSA for OH.-radicals kBSA [BSA] was
      kept constant. at 7.8 x 10(5) s-1, when DNA (0.1 mg/ml) was irradiated under
      different gas conditions (air, N2 and N2O), at pH 7 and 5 and with different
      ionic conditions. The resulting protein radicals react with DNA producing DNA
      protein crosslinks and DNA double-strand breaks. The yield and the kind of DNA
      damage depend on the nature of the protein radicals and their association with
      DNA. High phosphate concentration prevents the association of BSA with DNA and
      causes a reduction of the protection by BSA against double-strand break-age of
      DNA. Radiolysis in the presence of BSA in perchlorate solution leads to more
      strand breakage and less protein crosslinking than in phosphate solution because
      perchlorate is more chaotropic than phosphate. Changing the pH from 7 to 5
      increases the protection by BSA against DNA strand breakage.

PMID- 9191901
TI  - Gamma-irradiation and UV-C light-induced lipid peroxidation: a Fourier transform
      infrared absorption spectroscopic study.
AB  - Fourier transform-infrared spectroscopy of dry, multibilayer films has been used
      to study gamma-radiation and UV-C light induced lipid peroxidation in 1,2
      dilinoleoyl-sn-glycero-3-phosphocholine liposomes. The observed spectral changes
      were compared with the results obtained from measurement of hydroperoxides,
      conjugated dienes and to the formation of thiobarbituric acid reactive
      substances, such as malondialdehyde (MDA) or MDA-like substances. Upon
      irradiation a decrease in intensity of the asymmetric C - H stretching vibration
      (va(CH2)) of the isolated cis C = C - H groups (3010 cm-1) was observed. Directly
      correlated with the decrease of the va(CH2) absorption was a shift of the
      asymmetric phosphate ester stretching vibration (va(P = O)) towards smaller
      wavenumbers (1260-->1244 cm-1), indicating that the lipid peroxidation induced
      molecular alterations in the fatty acid chains influence the packing of the
      phospholipids in dry multibilayer films. In addition, the formation of a new
      absorption band at 1693 cm-1 could be detected, the intensity of which was
      comparable with the formation of thiobarbituric acid reactive substances and,
      therefore, attributed to the (C = O) stretching of alpha, beta unsaturated
      aldehydes. Dose-dependent studies using ionizing radiation showed that the
      decrease of va(CH2) was directly correlated with an increase in absorption of the
      conjugated dienes at 234 nm and with the formation of hydroperoxides suggesting
      that the absorption at 3010 cm-1 is solely due to isolated cis C = C - H groups
      and hence subject to the early stages of the radical chain reaction. UV-C light
      induced lipid peroxidation revealed a non-linear decrease of I3010, which was
      directly correlated with the formation of hydroperoxides. The observed early
      saturation of the conjugated dienes was attributed to an early photodecomposition
      of the conjugated double bonds.

PMID- 9191902
TI  - The number of clonogenic cells in crypts in three regions of murine large
      intestine.
AB  - Data are presented for the kinetics of repair of sub-lethal damage in the large
      intestine of mice. The results are based on experiments using the crypt
      microcolony assay with two equal sized doses which were delivered with a variable
      interval of time between the doses. These show that this split-dose repair was
      largely complete after 5 h, and that there were no significant differences
      between three regions of the large intestine. Overall the half-time for the
      repair was 2.3 +/- 0.8 h, and the maximum split-dose repair ratio (the proportion
      of damage recovered by splitting the dose into two fractions) was 22 +/- 2% and
      the mean recovery factor (the ratio of the number of surviving crypts using long
      interfraction intervals to that at zero time) was 11 +/- 2. The split-dose
      approach (Hendry 1979) using a 5 h interval has been used to estimate the number
      of clonogenic cells in large intestinal crypts. A range of single and paired
      doses between 7 Gy and 10.5 Gy were used. There were significant differences
      between the three regions of the large intestine, the caecum, mid-colon and
      rectum. The estimate of the number of clonogens also depended in a significant
      way on the dose of radiation used to make the estimate. At low doses large
      intestinal crypts contain between 5 and 10 clonogenic cells while if high doses
      were used they contain an estimated 16 to 36 clonogenic cells. Considerable
      similarity exists between the small intestine and the large intestine for; (a)
      the repair kinetics (b), the clonogenic estimates, and (c) their dependence on
      dose.

PMID- 9191903
TI  - Changes in gut neurotensin and modified colonic motility following whole-body
      irradiation in rat.
AB  - Exposure to ionizing radiation induces gastrointestinal dysfunction often
      associated with disorders of intestinal motility. Neurotensin is one of the
      mediators involved in the control of intestinal muscle activity. The aim of this
      study was to relate neurotensin tissue content and specific receptor binding with
      contractile effect of neurotensin in rat colon after irradiation. Rats were
      exposed to whole-body gamma-irradiation (60Co; 6 Gy). Intestinal (caecum, colon)
      neurotensin-like immunoreactivity, colonic muscle neurotensin receptor binding
      and neurotensin-induced contractions in isolated colon were investigated 3 and 7
      days after irradiation. Irradiation produced a marked increase in the intestinal
      muscle content of neurotensin-like immunoreactivity (2.5-fold in caecum, 5-fold
      in colon) 3 days post-irradiation. At 7 days, the intestinal neurotensin content
      was close to that of the control values. Three days after irradiation,
      neurotensin receptors in colonic muscle were characterized by the appearance of a
      transient second class of sites of low affinity-high capacity. A three-fold
      increase in the total number of sites was observed. In addition, effects of
      neurotensin on isolated colon preparations showed an increase (37%) of potency
      but a decrease (7-fold) of efficacy. Seven days after irradiation, the efficacy
      was close to the control. Modifications of intestinal neurotensin content and
      specific receptor characteristics induced by irradiation can influence the
      colonic contractile activity.

PMID- 9191904
TI  - The risk of non-melanoma skin cancer incidence in the Japanese atomic bomb
      survivors.
AB  - The latest Japanese atomic bomb survivor non-melanoma skin cancer incidence
      dataset is analysed and indicates substantial curvilinearity in the dose-response
      curve, consistent with a possible dose threshold of about 1 Sv, or with a dose
      response in which the excess relative risk is proportional to the fourth power of
      dose, with a turning-over in the dose-response at high doses (> 3 Sv). The time
      distribution of the radiation-induced excess risk is best described by a model in
      which the relative excess risk is proportional to a product of powers of time
      since exposure and attained age. The fits of generalized relative risk models
      with exponential functions of time and age at exposure (and in particular of
      attained age) to adjust the relative risk are less satisfactory, as also are the
      fits of other models in which products of powers of time since exposure, age at
      exposure and attained age adjust the excess absolute risk. Sensitivity analyses
      indicate the importance of likely adjustments to the Hiroshima neutron doses for
      the optimal model parameters, particularly if values of the neutron relative
      biological effectiveness (RBE) of more than 5 are assumed. If adjustments
      recently proposed are made to the Hiroshima neutron doses, then using the optimal
      model (in which excess risk is proportional to the fourth power of dose) the best
      estimate of the neutron RBE is 1.3 (95% CI < 07.1). However, uncertainties in
      skin dose estimates for the atomic bomb survivors means that the findings with
      respect to the neutron RBE and the non-linearity in the dose-response curve
      should be treated with caution.

PMID- 9191905
TI  - Analysis of cancer mortality among atomic bomb survivors registered at Hiroshima
      University.
AB  - The aim of this study was to investigate the late effect on cancer mortality risk
      of the radiation exposure of atomic bomb survivors who comprised a study
      population different from that previously studied by the Radiation Effects
      Research Foundation (RERF). We examined survivors residing in Hiroshima
      Prefecture, who were followed up between 1968 and 1989 by the Research Institute
      for Radiation Biology and Medicine (RIRBM) at Hiroshima University. We used the
      dose-evaluation system known as Atomic Bomb Survivors 1993 Dose (ABS93D), which
      was based on the Dosimetry System 1986 for the survivors registered with RERF.
      The dose estimation was applied in a total of 35,123 subjects. Among survivors
      who had been alive for > 20 years after the bombing, the relative mortality risk
      of leukaemia at 1 Gy of organ dose was 2.37 (90% confidence interval: 1.36-3.39),
      which was significantly higher than the zero dose control group. Similarly,
      significantly higher risks were observed for all cancers except leukaemia,
      including cancers of the lung, colon and female breast. Comparison is made with
      RERF results regarding temporal changes in the relative risk. Although we
      observed slightly lower relative risks than RERF values for the cancer of the
      stomach and lung, and for all cancer except leukaemia, no marked trends for any
      cancer were observed in this study. Though there were some differences in
      population between RERF and RIRBM, no marked discrepancies were observed.

PMID- 9191906
TI  - Evaluation of the efficiency of DTPA and other new chelating agents for removing
      neptunium from target organs.
AB  - Diethylenetriamine pentaacetic acid (DTPA) has been tested with 8 other new
      chelators for neptunium decorporation after systemic contamination in the rat.
      The ligands were injected intravenously at a dosage of 30 mumol kg-1 and the
      animals killed 24 h later. The results show that none of the chelators tested was
      efficient in removing significant amounts of the radionuclide from the body. In
      order to understand why these chelators were ineffective, in vitro approaches
      have since been developed in which high concentrations of DTPA were added to Np
      bearing ligands in the blood, liver and skeleton. The main conclusions were that
      under our experimental conditions neptunium was not chelatable after its organ
      deposition.

PMID- 9191907
TI  - Research strategies for the prevention of early events in human radiation
      carcinogenesis. Report on the 7th LH Gray Workshop held in the Radiation Science
      Centre, Dublin from 5th-8th December 1996.

PMID- 9191908
TI  - Destabilization of potato spindle tuber viroid by mutations in the left terminal
      loop.
AB  - Infectivity studies with highly infectious RNA inocula generated by ribozyme
      cleavage were used to compare the biological properties of three apparently
      nonviable mutants of potato spindle tuber viroid (PSTVd). One of these mutants
      (PSTVd-P) contains three nucleotide substitutions in the left terminal loop, and
      mechanical inoculation of tomato seedlings with RNA transcripts at levels
      equivalent to 10(3)-10(5) times the ID50 for PSTVd-Intermediate failed to result
      in systemic infection. Viable progeny containing a spontaneous C-->G change at
      position 4 could, however, be recovered from transgenic Nicotiana benthamiana
      plants that constitutively expressed PSTVd-P RNA. The initial mutations in PSTVd
      P led to an overall weakening of its native structure in vitro, and the precisely
      full-length molecule released by ribozyme cleavage in vivo was also unstable.
      Even RT-PCR analysis failed to reveal detectable amounts of circularized PSTVd-P
      among the RNAs isolated from uninfected plants. Predicted stabilizing effects of
      a spontaneous mutation at position 4 suggest that the appearance of viable
      progeny was dependent on a combination of events: errors by host RNA polymerase
      II during transcription of the mutant transgene coupled with a strong selective
      pressure against alterations in the native structure of PSTVd.

PMID- 9191909
TI  - Evidence for heterologous encapsidation of potato spindle tuber viroid in
      particles of potato leafroll virus.
AB  - The aphid Myzus persicae (Sulz.) was shown to transmit potato spindle tuber
      viroid (PSTVd) to potato clone DTO-33 from source plants doubly infected with
      potato leafroll virus (PLRV) and PSTVd. Transmission was of the persistent type
      and did not occur when the insects were allowed to feed on singly infected
      plants. Only low levels of PSTVd were associated with purified PLRV virions, but
      its resistance to digestion with micrococcal nuclease indicates that the viroid
      RNA is encapsidated within the PLRV particles. Epidemiological surveys carried
      out at three locations in China revealed a strong correlation between PSTVd
      infection and the presence of PLRV, suggesting that PLRV can facilitate PSTVd
      spread under field conditions.

PMID- 9191910
TI  - Presentation of a foreign peptide on the surface of tomato bushy stunt virus.
AB  - A 13-amino-acid peptide derived from the V3 loop of human immunodeficiency virus
      (HIV-1) glycoprotein 120 (gp120) was attached as a C-terminal gene fusion to the
      coat protein of tomato bushy stunt virus (TBSV). The architecture of this plant
      virus permitted external display of the foreign sequence 180 times on the surface
      of the chimaeric virus particle. The chimaera replicated to a level similar to
      wild-type TBSV and the foreign sequence was retained through six sequential
      passages in plants. The HIV epitope was detected on the surface of the virus
      capsid by a V3-specific monoclonal antibody and by human sera from HIV-1-positive
      patients, demonstrating the potential of using plant-derived chimaeric particles
      for diagnostic purposes. Chimaeric virus also induced a specific immune response
      to the foreign HIV epitope when injected into NMRI mice.

PMID- 9191911
TI  - Molecular analysis of the pothos latent virus genome.
AB  - Pothos latent virus (PoLV) is an isometric virus with a positive-sense, single
      stranded RNA genome of 4415 nt. The genome contains five open reading frames
      (ORF), coding for five proteins with approximate molecular masses of 25, 84, 40,
      27 and 14 kDa, respectively. In vitro synthesized PoLV RNA was infectious to
      Nicotiana benthamiana plants and protoplasts, but could not support replication
      of the defective interfering (DI) and satellite RNAs associated with Cymbidium
      ringspot tombusvirus. No DI RNA related to PoLV was generated after repeated
      passaging with infected sap. Mutagenesis studies defined the role of the ORF 4
      product (27 kDa) as a movement protein, and the ORF 5 product (14 kDa) as being
      responsible for symptom severity. Moreover, it was shown that the coat protein
      (CP) is important in regulating synthesis of the 14 kDa protein, excess
      production of which is lethal to infected plants. CP mutants defective in capsid
      formation infected plants systemically and induced severe necrotic symptoms.
      Conversely, CP mutants able to form apparently normal virus particles induced
      symptoms indistinguishable from those elicited by wild-type virus.

PMID- 9191912
TI  - Secondary structure-dependent evolution of Cymbidium ringspot virus defective
      interfering RNA.
AB  - Mutational analysis of defective interfering (DI) RNAs of Cymbidium ringspot
      virus (CymRSV) was used to study the mechanism of DI RNA evolution. It was shown
      that a highly base-paired structure in the 3' region of the longer DI RNA
      directed the formation of smaller DI RNA molecules. Mutations which increased the
      stability of the computer-predicted, highly structured 3' region of the longest
      DI RNA of CymRSV significantly enhanced the generation and accumulation of the
      smaller derivatives. Sequence analysis of smaller progeny molecules revealed that
      the highly base-paired region was deleted from the precursor DI RNA. Moreover,
      sites of recombination were found in other regions of the DI RNA progenies due to
      transposition of the highly base-paired structure. It is likely that the deletion
      event was structure- and not sequence-specific, and operated when a foreign
      sequence containing a 37-nt-long base-paired stem was inserted at the appropriate
      position of DI RNA.

PMID- 9191913
TI  - Complete nucleotide sequence of tobacco necrosis virus strain DH and genes
      required for RNA replication and virus movement.
AB  - The complete genome sequence of tobacco necrosis virus strain D (Hungarian
      isolate, TNV-DH) was determined. The genome (3762 nt) has an organization
      identical to that reported for TNV-D. Highly infectious synthetic transcripts
      from a full-length TNV-DH cDNA clone were prepared, the first infectious
      necrovirus transcript reported. This clone was used for reverse genetic studies
      to map the viral genes required for replication and movement. Protoplast
      inoculation with delta 22 and delta 82 mutants revealed that both the 22 kDa and
      82 kDa gene products are required for RNA replication. Although the products of
      three small central genes (p7(1), p7a and p7b) were not essential for RNA
      replication in protoplasts, mutations in these ORFs prevented infection of
      plants. In contrast, viral RNA accumulation and cell-to-cell movement were
      observed in the inoculated, but not the systemically infected, leaves of
      Nicotiana benthamiana challenged with RNA lacking the intact coat protein (CP)
      gene. These results strongly suggest that p7(1), p7a, p7b and CP are involved in
      TNV-DH cell-to-cell and long-distance movement, respectively.

PMID- 9191914
TI  - Movement protein-derived resistance to triple gene block-containing plant
      viruses.
AB  - Two mutant potato virus X (PVX) movement protein (MP) genes (m 12K-Sal and m 12K
      Kpn) were obtained by inserting specific linkers at the boundary between the N
      terminal hydrophobic and putative transmembrane segment, and the central
      invariant hydrophilic region of the respective 12 kDa, 12K, triple gene block
      (TGB) protein. Several transgenic potato lines which expressed m 12K-Sal or m 12K
      Kpn to different degrees were resistant to infection by PVX, potato aucuba mosaic
      potexvirus and the carlaviruses potato virus M and S over a wide range of
      inoculum concentrations (3-300 micrograms/ml). However, they were not resistant
      to potato virus Y, which lacks a TGB protein. We suggest that the resistance of m
      12K-Sal and m 12K-Kpn transgenic potato lines is MP-derived and not RNA-mediated.

PMID- 9191915
TI  - Mutation of the GKS motif of the RNA-dependent RNA polymerase from potato virus X
      disables or eliminates virus replication.
AB  - The RNA-dependent RNA polymerase (RdRp) of potato virus X (PVX) contains a
      glycine-lysine-serine (GKS) motif. This motif is present in the replication
      enzyme of many RNA viruses and is thought to be required for nucleoside
      triphosphate-binding. Three single amino acid changes, glycine to alanine (AKS),
      lysine to asparagine (GNS) and lysine to glutamate (GES) within the GKS motif of
      the PVX RdRp were tested for their effect on PVX accumulation. The GNS and GES
      mutations rendered the virus unable to accumulate in either tobacco plants or
      protoplasts, whereas substitution of glycine with alanine had only a minor effect
      on accumulation of PVX. The glycine to alanine mutation reverted to wild-type
      after passage on Nicotiana clevelandii plants. These findings suggest that the
      GKS motif is required for PVX replication and that strong selection pressures are
      active to maintain necessary sequences of the viral RdRp.

PMID- 9191916
TI  - Analysis of the sequence diversity of the P1, HC, P3, NIb and CP genomic regions
      of several yam mosaic potyvirus isolates: implications for the intraspecies
      molecular diversity of potyviruses.
AB  - Partial sequences from serologically characterized yam mosaic potyvirus (YMV)
      isolates were determined in conserved (helper-component proteinase, HC; nuclear
      inclusion b, NIb) and variable (first protein, P1; third protein, P3; and coat
      protein, CP) regions of the potyviral genome in order to investigate the
      intraspecies molecular diversity of YMV. Multiple sequence alignments and
      pairwise comparisons were used to quantify the sequence polymorphism in these
      regions. Two levels of diversity were observed among YMV isolates: above 90%
      nucleotide (nt) sequence identities were found between YMV isolates of the same
      group (intragroup) regardless of the region considered, whereas identities
      between isolates from different groups (intergroup) were lower and depended upon
      the protein chosen. For instance, the average intergroup nt sequence identity
      between YMV isolates was about 65% in the P1 protein and the N terminus of the CP
      while there was more than 80% nt identity in the HC, P3 and NIb proteins. Thus P3
      appeared to be conserved between YMV isolates even though this region was
      variable between potyvirus species. Similar analysis of the intraspecies
      molecular diversity of other potyviruses (potato virus Y, zucchini yellow mosaic
      virus, plum pox virus, pea seed-borne mosaic virus) led to the same results: (i)
      two levels of intraspecies molecular diversity were found (intragroup and
      intergroup); (ii) intraspecies molecular diversity differed from interspecies
      molecular diversity in the P3, P1 and N-terminal regions.

PMID- 9191917
TI  - Maize streak virus coat protein binds single- and double-stranded DNA in vitro.
AB  - Maize streak virus (MSV) coat protein (CP) is required for virus movement within
      the plant. Deletion or mutation of MSV CP does not prevent virus replication in
      single cells or protoplasts but leads to a loss of infectivity in the inoculated
      plant. The mechanism by which MSV CP mediates the transfer of MSV DNA from cell
      to cell and through the vascular bundle is still unknown. Towards understanding
      the role of MSV CP in virus movement, the interaction of the CP with viral DNA
      was investigated using the 'south-western' assay. Wild-type and truncated MSV CPs
      were expressed in E. coli and the expressed CPs were used to investigate
      interactions with single-stranded (ss) and double-stranded (ds) DNA. The results
      showed that MSV CP bound ss and ds viral and plasmid DNA in a sequence non
      specific manner. The binding domain was mapped to within the 104 N-terminal amino
      acids of the MSV CP. We propose that the binding of CP to MSV DNA is involved in
      viral DNA nuclear transport as well as encapsidation and thus may have a role in
      intra- and inter-cellular movement as well as systemic infection.

PMID- 9191918
TI  - Replication of wild-type and mutant clones of satellite tobacco mosaic virus in
      Nicotiana benthamiana protoplasts.
AB  - RNA transcribed from cloned satellite tobacco mosaic virus (STMV) cDNA replicated
      in Nicotiana benthamiana protoplasts when co-inoculated with tobacco mild green
      mosaic virus (TMGMV) genomic RNA, but degraded when inoculated alone. STMV
      genomic RNA extracted from wild-type virions replicated in protoplasts when co
      inoculated with TMGMV, tobacco mosaic virus (TMV) or tomato mosaic virus (ToMV).
      Transcripts from clones of two STMV coat protein (CP) mutants accumulated to the
      same level as wild-type transcripts in protoplasts when co-inoculated with TMGMV,
      whereas a third mutant accumulated to detectable levels in some, but not all,
      experiments. These results confirm that STMV RNA requires helper virus for
      replication, and that the helper specificity exhibited by cloned STMV reflects a
      specific requirement for the TMGMV replicase. It also demonstrates that the low
      accumulation of STMV CP mutants observed previously in whole plants cannot be
      attributed to inefficient RNA replication.

PMID- 9191919
TI  - Trans-acting untranslated elements of groundnut rosette virus satellite RNA are
      involved in symptom production.
AB  - Isolates of groundnut rosette umbravirus (GRV) contain a satellite RNA (sat-RNA),
      about 900 nucleotides (nt) in length, different variants of which are responsible
      for the symptoms of different forms of rosette disease in groundnuts and, in the
      particular instance of sat-RNA YB3b, for the production of yellow blotch symptoms
      in Nicotiana benthamiana. Sat-RNA YB3b does not affect the accumulation of GRV
      genomic or subgenomic RNAs in infected plants. Replication of sat-RNA YB3b and
      induction of yellow blotch symptoms do not require the production of any sat-RNA
      encoded proteins. Experiments with deletion mutants identified three functional
      untranslated elements in sat-RNA YB3b. One (designated R) comprises nt 47-281, is
      essential for sat-RNA replication and appears to be cis-acting. The other two
      (designated A and B) comprise nt 280-470 and 629-849, respectively, are both
      involved in yellow blotch symptom production and can act in trans. Element A
      contains the determinant that is unique to sat-RNA YB3b. The process of symptom
      induction by sat-RNA YB3b apparently involves a novel type of specific
      interaction of two untranslated RNA elements, which can complement each other,
      with a host factor or factors.

PMID- 9191920
TI  - The diversity of measles virus in the United Kingdom, 1992-1995.
AB  - Three distinct genotypes were identified amongst 50 measles virus (MV) strains
      characterized in the UK between 1992 and 1995 by direct sequencing of the RT-PCR
      products amplified from clinical specimens. All three genotypes were related to
      viruses previously reported in the United States or in continental Europe.
      Phylogenetic analyses of 255 and 152 nucleotide sequences from the N and M genes,
      respectively, generated very similar lineages. The degree of divergence between
      genotypes was 3.5-16% and 2.6-7.9% in the N and the M genes, respectively. MV
      genotypes which circulated during the 1970s and 1980s in the UK were not detected
      in this period. Comparison of the C-terminal regions of the N gene sequences of
      UK strains isolated or detected between 1974 and 1995 suggests that there have
      been multiple genotypes of MV circulating in the UK over the past 20 years.

PMID- 9191921
TI  - Antibodies to a new linear site at the topographical or functional interface
      between the haemagglutinin and fusion proteins protect against measles
      encephalitis.
AB  - The haemagglutinin protein (H) of measles virus (MV) binds to susceptible cells
      and collaborates with the fusion protein (F) to mediate fusion of the virus with
      the cell membrane. Binding and fusion activity of the virus can be monitored by
      haemagglutination and haemolysis, respectively, of monkey erythrocytes. Most
      monoclonal antibodies (MAbs) with haemolysis inhibiting activity (HLI+) are
      either MV-F specific and do not inhibit haemagglutination (HI-), or they bind to
      MV-H and are HI+ by interfering with virus binding. We describe here a small
      panel of H-specific MAbs (BH47, BH59, BH103, BH129) which bind to a new linear
      neutralizing epitope, H244-250 (SELSQLS; NE domain), and which prevent virus-cell
      fusion (HLI+) but not virus binding (HI-). These antibodies also protect against
      MV encephalitis in an animal model. They do not compete with an HLI+/HI+ antibody
      (BH216) which binds to the haemagglutinin noose epitope (HNE). The antibodies
      described here and the HNE-specific antibodies are functionally distinct and
      define two topographically non-overlapping interfaces, supposedly with a bias
      towards the host cell MV-receptor and the fusion protein respectively. The
      proximity of the CD46 downregulating amino acid Arg-243 may suggest a functional
      link between the domain described here and the CD46 binding domain. This new
      protective linear site is also of potential interest for the design of a subunit
      based vaccine.

PMID- 9191922
TI  - Human parainfluenza virus type 2 phosphoprotein: mapping of monoclonal antibody
      epitopes and location of the multimerization domain.
AB  - The epitopes recognized by 42 monoclonal antibodies directed against the human
      parainfluenza virus type 2 (hPIV-2) phosphoprotein (P) were mapped on the primary
      structure of the P protein by testing their reactivities with deletion mutants.
      By Western Immunoblotting with these monoclonal antibodies and P protein deletion
      mutants the region essential for P-P interactions was determined. The P protein
      region encompassing amino acids 211-248 was required for proper folding and
      oligomerization which is mediated by predicted coiled-coils in this region. The
      oligomer was shown to be a homotrimer by chemical cross-linking experiments.

PMID- 9191923
TI  - Genome organization and transcription strategy in the complex GNS-L intergenic
      region of bovine ephemeral fever rhabdovirus.
AB  - A 1622 nucleotide region of the bovine ephemeral fever virus (BEFV) genome,
      located between the second glycoprotein (GNS) gene and the polymerase (L) gene,
      has been cloned and sequenced in Australian (BB7721) and Chinese (Beijing-1)
      isolates of the virus. In the Australian isolate, the region contains five long
      open reading frames (ORFs) organized into three coding regions (alpha, beta and
      gamma), each of which are bound by a consensus transcription initiation and
      transcription termination-polyadenylation-like sequences. The alpha coding region
      contains three long ORFs (alpha 1, alpha 2 and alpha 3). The alpha 1 ORF encodes
      a 10.6 kDa polypeptide which contains hydrophobic and highly basic regions
      characteristic of a viroporin. The alpha 2 ORF encodes a 13.7 kDa polypeptide and
      overlaps the alpha 3 ORF which encodes a 5.7 kDa polypeptide. The beta coding
      region contains a single long ORF encoding a polypeptide of 12.2 kDa. The gamma
      coding region, which does not occur in Adelaide River virus (ARV), contains a
      single long ORF encoding a polypeptide of 13.4 kDa. The Chinese isolate shares
      91% nucleotide sequence identity with the Australian isolate. The organization of
      the alpha, beta and gamma coding regions is preserved and the sequences of the
      encoded polypeptides are similar to those of BB7721. The major transcription
      products of the region were identified in BB7721 as polycistronic alpha (alpha 1
      alpha 2-alpha 3) and beta-gamma mRNAs. Sequence similarities in the BEFV alpha
      beta and beta-gamma gene junctions, and the gamma-L and beta-L gene junctions of
      BEFV and ARV, suggest that the gamma gene may have evolved from the beta-gene by
      sequence duplication.

PMID- 9191924
TI  - Nucleotide sequence of the glycoprotein gene of viral haemorrhagic septicaemia
      (VHS) viruses from different geographical areas: a link between VHS in farmed
      fish species and viruses isolated from North Sea cod (Gadus morhua L.).
AB  - RT-PCR methods have been applied to the detection and sequencing of the
      glycoprotein gene of viral haemorrhagic septicaemia virus (VHSV), the rhabdovirus
      which causes viral haemorrhagic septicaemia (VHS) in farmed salmonid fish.
      Phylogenetic analysis of a 360 nt region of the glycoprotein gene from a range of
      marine and fresh water VHSV isolates identified three genogroups, I-III.
      Significantly, two virus isolates recovered from ulcerated North Sea cod caught
      off the Shetland Islands, and an isolate recovered from diseased turbot farmed on
      the island of Gigha, Scotland were assigned to the same genogroup. Moreover, a
      virus isolated from diseased turbot farmed on the Baltic Sea coast shared 99.4%
      nucleotide sequence similarity with a virus associated with a VHS outbreak in
      rainbow trout. This is the first time that a genetic link between a VHS outbreak
      and natural VHSV infections of marine fish species has been demonstrated.

PMID- 9191925
TI  - A highly cytopathogenic influenza C virus variant induces apoptosis in cell
      culture.
AB  - An influenza C virus variant, C/AA-cyt, was identified as the agent responsible
      for highly effective induction of cytopathogenicity in MDCK cells. The
      cytopathogenic effect was manifested by cell rounding, cell shrinkage and foci of
      cell destruction leading finally to disruption of the monolayer in a virus dose
      dependent manner. Virus-induced cytopathogenicity was suppressed by temperatures
      nonpermissive for virus replication. Maintenance of plasma membrane integrity
      post-infection, in connection with induction of a DNA fragmentation ladder,
      revealed the characteristic picture of apoptosis. In support of this,
      quantitative analysis demonstrated high levels of apoptosis-like oligonucleosomal
      DNA. The results indicate that influenza C viruses can induce programmed cell
      death, as formerly reported for influenza type A and B viruses.

PMID- 9191926
TI  - Analysis of hepatitis C virus core protein interaction domains.
AB  - Hepatitis C virus (HCV) core protein forms the internal viral coat that
      encapsidates the genomic RNA and is enveloped in a host cell-derived lipid
      membrane. As the single capsid protein, core should be capable of multimerization
      but attempts to produce virus-like particles following expression of HCV
      structural proteins have not been successful. In this study, we have analysed the
      interaction capacity of full-length and truncated HCV core using the yeast two
      hybrid system. Full-length core containing or lacking the translocation signal
      for the E1 glycoprotein did not interact with full-length or truncated core
      proteins. Truncation to the N-terminal 122 aa revealed an interaction domain
      which was mapped to the tryptophan-rich sequence from aa 82-102 and was termed
      the main homotypic interaction domain. The C-terminal hydrophobic fragment of
      core (aa 122-172) was incapable of interacting with itself but interacted with
      the main homotypic interaction domain in trans (the weak heterotypic interaction
      domain). Core proteins truncated at their N and C termini (aa 46-102) were trans
      activating when fused to the DNA-binding domain of GAL4. Based on our results, we
      suggest that the C-terminal segment may interact in cis with the main homotypic
      interaction domain and thereby prevent multimerization. Core-core interaction was
      also observed for in vitro-translated proteins bound to truncated immobilized
      core 102. However, interaction was less specific in this system suggesting that
      protein interaction and possibly conformational alteration of core may be
      dependent on the experimental system.

PMID- 9191927
TI  - Complete nucleotide sequence of a type 4 hepatitis C virus variant, the
      predominant genotype in the Middle East.
AB  - Hepatitis C virus (HCV) type 4 is the predominant genotype found throughout the
      Middle East and parts of Africa, often in association with high population
      prevalence as in Egypt. To investigate more fully its evolutionary relationship
      with other genotypes of HCV, and to study its overall genome organization, we
      have determined the entire sequence encompassing the coding region of the
      genotype 4a isolate ED43, obtained from an HCV-infected individual from Egypt.
      The sequence of ED43 contained a single open reading frame encoding a polyprotein
      of 3008 amino acids (aa), smaller than that reported for other HCV genotypes
      which vary from 3010 aa to 3037 aa. The nucleotide and amino acid sequences were
      compared with the full-length sequences already reported for genotypes 1a, 1b,
      1c, 2a, 2b, 2c, 3a, 3b and those of isolates JKO49 and JKO46 described as types
      10a and 11a. The differences in length of the polyprotein originated in variable
      regions in the E2 and NS5A genes. The complete sequence of ED43 confirmed the
      classification of type 4 as a separate major genotype.

PMID- 9191928
TI  - Genetic variation among strains of wild-type yellow fever virus from Senegal.
AB  - We have examined and compared at the molecular level three strains of wild-type
      yellow fever (YF) virus isolated from Senegal in 1927, 1953 and 1965, termed
      French viscerotropic virus, Rendu and Dak1279 respectively. Over the structural
      protein genes, Rendu differed from the other two strains by 8% at the nucleotide
      level. Rendu also differed antigenically, possessing a 'vaccine'-specific
      envelope (E) protein epitope (i.e. an epitope previously shown to be found on 17D
      and French neurotropic vaccine viruses only and not wild-type strains of YF
      virus). Consequently, we propose that at least two distinct genotypes of wild
      type YF virus have been present in Senegal. Since Rendu virus was isolated from a
      fatal case of YF, it would indicate that the vaccine-specific epitope on the E
      protein is not associated with attenuation of the viscerotropism of wild-type YF
      virus.

PMID- 9191929
TI  - Yellow fever virus envelope protein has two discrete type-specific neutralizing
      epitopes.
AB  - Two monoclonal antibody neutralization resistant (MAbR) variants of the yellow
      fever (YF) 17D-204 vaccine virus strain were selected using YF type-specific MAb
      B39. These B39R variants were compared with the variant virus selected by Lobigs
      et al. (Virology 161, 474-478, 1987) using a second YF-type specific MAb (2E10)
      which mapped to amino acid position 71/72 in the envelope (E) protein.
      Neutralization assays with a panel of MAbs suggested that these two YF-type
      specific epitopes are located in two discrete regions of the folded E protein.
      Each of the B39R variants had a single nucleotide mutation which encoded an amino
      acid substitution at either position E-155 or E-158. Thus, YF type-specific
      epitopes map to both domain I (B39) and II (2E10) of the YF virus E protein. The
      B39 defined epitope represents the first flavivirus neutralizing epitope
      localized to this region of domain I of the E protein.

PMID- 9191930
TI  - Phylogenetic analysis of pestiviruses from domestic and wild ruminants.
AB  - Infections with pestiviruses occur in cattle, sheep, pigs and also in numerous
      other ungulate species. In the present study, pestiviruses from goat, buffalo,
      deer and giraffe were analysed at the molecular level; unusual strains from
      cattle and pigs were also included. A phylogenetic analysis of the respective
      pestiviruses was undertaken on the basis of a fragment from the 5' noncoding
      region as well as the gene encoding autoprotease Npro. Statistical analyses of
      the respective phylogenetic trees-based on the 5' NCR revealed low confidence
      levels for most of the branches, while the structure of the tree based on the
      Npro gene was supported by high bootstrap values. Accordingly, the isolates from
      goat, buffalo and deer can be grouped together with bovine viral diarrhoea virus
      (pestivirus type 1); within this genotype three subgroups and one disparate virus
      have been identified. One isolate from pig and one from cattle belong to the
      group of 'true' border disease virus (pestivirus type 3), which can be further
      subdivided into two major subgroups. Interestingly, the giraffe isolate does not
      belong to one of the four established pestivirus genotypes. The phylogenetic
      analysis strongly suggests that genotype 1 pestiviruses occur world-wide in many
      ruminant species. Furthermore, phylogenetic trees based on the Npro gene
      nucleotide sequences show that the respective sequences do not segregate into
      discrete lineages based on host-species origin.

PMID- 9191931
TI  - Solubilized and cleaved VP7, the outer glycoprotein of rotavirus, induces
      permeabilization of cell membrane vesicles.
AB  - It has been previously shown that rotavirus triple-layered particles induce
      permeabilization of liposomes and membrane vesicles. These effects were mediated
      by one or both of the solubilized outer-capsid proteins, VP4 and VP7.
      Permeabilization was dependent on trypsin treatment of the viral particles,
      suggesting that VP4 was involved. To analyse the respective roles of the outer
      capsid proteins in this permeabilization process, we have used membrane vesicles
      loaded with carboxyfluorescein and virus-like particles derived from insect cells
      co-expressing various sets of capsid proteins. Virus-like particles containing
      VP2, VP6 and VP7 (VLP2/6/7) are as efficient in permeabilizing vesicles as triple
      layered particles. As with double-layered particles, virus-like particles made of
      VP2 and VP6 had no effect on vesicle permeabilization. Permeabilization of
      membrane vesicles required trypsinization of the VP7 solubilized from VLP2/6/7.
      These results show that solubilized and trypsinized VP7 is able to induce
      membrane permeabilization, independently of the presence of VP4.

PMID- 9191932
TI  - A novel human rotavirus serotype with dual G5-G11 specificity.
AB  - Rotavirus serotype G5 isolates were recently recovered from children with
      diarrhoea in Brazil. Like most human strains, they exhibited long
      electropherotypes and subgroup II and Wa-like VP4 specificity. We report the
      successful propagation and the molecular and antigenic characterization of one of
      these isolates (IAL-28). Cross-neutralization of IAL-28 and a single gene
      reassortant, UK x IAL-28, which contains the gene encoding the IAL-28 VP7 in the
      UK genomic background, with prototype G1 to G14 rotaviruses demonstrated that IAL
      28 has antigenic determinants specific for both G5 and G11 serotypes. Sequence
      analysis of the gene encoding VP7 suggested that one or two amino acid
      substitutions at positions 96 and 100 on IAL-28 VP7 were possibly responsible for
      the additional G11 specificity. G5 rotaviruses are found in horses and
      predominate in piglets, whereas G11 has been identified exclusively as a swine
      pathogen.

PMID- 9191933
TI  - Cloning, sequence analysis and expression of the major outer capsid protein gene
      of an aquareovirus.
AB  - The nucleotide and deduced amino acid sequences of genome segment 10 of
      aquareovirus strain SBR, encoding the major outer capsid protein (VP7), have been
      determined. Genome segment 10 of SBR virus is 986 nucleotides long and encodes a
      polypeptide of 298 amino acids with a predicted molecular mass of 32,430 Da.
      There are 26 non-translated nucleotides at the 5' end and 66 non-translated
      nucleotides at the 3' end. Using a recombinant baculovirus system, the VP7
      protein of SBR virus was expressed to a high level. The baculovirus-produced VP7
      protein was similar both in its size and antigenic properties to the authentic
      aquareovirus VP7 protein. Antiserum from a rabbit immunized with the baculovirus
      produced VP7 protein failed to neutralize the homologous aquareovirus strain. As
      determined by Western blotting, this antiserum reacted with aquareovirus strains
      belonging to the same genogroup as SBR virus, but did not react with aquareovirus
      strains belonging to the other genogroups.

PMID- 9191934
TI  - Identification of a new genogroup of aquareovirus by RNA-RNA hybridization.
AB  - The relative mobilities of the 11 dsRNA genomic segments of 22 aquareovirus
      isolates from fish and shellfish obtained from different geographical areas of
      the world were compared by PAGE. Using reciprocal RNA-RNA dot blot hybridization,
      a new sixth genetic group of aquareovirus (genogroup F) was identified. Genogroup
      A was represented by eight and genogroup B by 12 isolates. The remaining two
      isolates represented the new sixth genogroup (genogroup F). The genetic
      relationship of these aquareoviruses with mammalian rotavirus group A (SA 11) was
      also examined by reciprocal RNA-RNA blot hybridization but none was found under
      any of the stringency conditions used.

PMID- 9191935
TI  - Degenerate and specific PCR assays for the detection of bovine leukaemia virus
      and primate T cell leukaemia/lymphoma virus pol DNA and RNA: phylogenetic
      comparisons of amplified sequences from cattle and primates from around the
      world.
AB  - Degenerate and specific PCR assays were developed for bovine leukaemia virus
      (BLV) and/or primate T cell leukaemia/lymphoma viruses (PTLV). The degenerate
      assays detected all major variants of the BLV/PTLV genus at a sensitivity of 10
      100 copies of input DNA; the specific systems detected 1-10 copies of input
      target. Sensitivity was 100% in specific DNA-PCR assays done on peripheral blood
      from seropositive BLV-infected cattle and HTLV-I- or HTLV-II-infected humans, and
      62% in RNA/DNA-PCR assays on sera from BLV seropositive cattle. The pol fragments
      from 21 different BLV strains, isolated from cattle in North and Central America,
      were cloned and sequenced, and compared to other published BLV and PTLV pol
      sequences. BLV and PTLV sequences differed by 42%. Sequence divergence was up to
      6% among the BLV strains, and up to 36% among the PTLV strains (with PTLV-I and
      PTLV-II differing among themselves by 15% and 8%, respectively). Some cows were
      infected with several BLV strains. Among retroviruses, BLV and PTLV sequences
      formed a distinct clade. The data support the interpretation that BLV and PTLV
      evolved from a common ancestor many millennia ago, and some considerable time
      before the PTLV-I and PTLV-II strains diverged from each other. The dissemination
      of the BLV strains studied probably resulted from the export of European cattle
      throughout the world over the last 500 years. The relatively similar mutation
      rates of BLV and PTLV, after their various points of divergence, suggest that
      there could be a much wider genetic range of BLV than has currently been defined.

PMID- 9191936
TI  - Identification and characterization of bovine herpesvirus-1 glycoproteins E and
      I.
AB  - To identify the products of the bovine herpesvirus-1 (BHV-1) gE and gI genes, we
      constructed baculovirus recombinants containing the putative gE or gI genes.
      These recombinant viruses synthesized BHV-1 gE and gI with apparent molecular
      masses of 84 and 41 kDa, respectively. Polyclonal antibodies against these
      recombinant gE or gI proteins were produced and by using these antibodies, we
      showed the presence of gE and gI with apparent molecular masses of 94 and 45 kDa,
      respectively, in purified BHV-1 virions. We also demonstrated that like their
      herpes simplex virus-1 and pseudorabies virus counterparts BHV-1 gE and gI form a
      complex. A gI- BHV-1 mutant failed to express gI but gE was found in the virions.
      On the other hand, neither gE nor gI was found in the virions of a gE- BHV-1
      mutant. In the gE- BHV-1 mutant, gI was produced but released into the medium
      without being integrated in the virions.

PMID- 9191937
TI  - Herpesvirus saimiri-immortalized human T-cells support long-term, high titred
      replication of human immunodeficiency virus types 1 and 2.
AB  - Herpesvirus saimiri strain C488 transforms human CD4+ T-lymphocytes to continuous
      interleukin-2-dependent growth. Unlike human T-cell lines derived from tumours or
      those transformed by human T-lymphotropic virus 1, herpesvirus saimiri
      immortalized T-cells (HVS T-cells) retain many functions of primary activated T
      lymphocytes. We have characterized the course of human immunodeficiency virus
      types 1 and 2 (HIV-1/-2) infection in three HVS T-cell lines. Our results confirm
      that HVS T-cells are highly permissive to both HIV-1/-2 prototype viruses and to
      poorly replicating HIV-2 strains of restricted cell tropism. However, the
      infection was persistently productive for up to 5 months. The down-regulation of
      surface CD4 molecules was delayed and virus yields significantly exceeded those
      obtained in T-cell lines.

PMID- 9191938
TI  - Identification of a cis-acting element within the herpesvirus saimiri ORF 6
      promoter that is responsive to the HVS.R transactivator.
AB  - We have previously demonstrated that two distinct transcripts are produced from
      ORF 50, the major transcriptional activating gene of herpesvirus saimiri. The
      products of these transcripts trans-activate the delayed-early ORF 6 promoter,
      though to different degrees. Deletion analysis demonstrated that the ORF 50
      responsive elements are contained in a 132 bp fragment situated 127-259 bp from
      the transcription initiation site within the ORF 6 promoter. This fragment
      conferred ORF 50-responsiveness on an enhancerless simian virus 40. Gel
      retardation analysis further mapped the responsive elements to a 38 bp fragment.

PMID- 9191939
TI  - Direct demonstration of persistent Epstein-Barr virus gene expression in
      peripheral blood of infected common marmosets and analysis of virus-infected
      tissues in vivo.
AB  - Epstein-Barr virus (EBV) infection in animal model systems has been studied
      previously in marmosets and tamarins using serology and PCR of saliva. Here we
      directly demonstrated long-term persistence of EBV in the peripheral blood of
      marmosets by assaying EBER RNA expression. A new reverse transcription-PCR assay,
      able to distinguish a naturally occurring strain polymorphism in EBER 2 that may
      be useful as a strain marker for monitoring persistence and interactions between
      multiple strains in the same animal or person, has been developed. In situ
      hybridization and immunohistochemistry have also been used to search for EBV
      infected cells in the animals. The carrier state in the common marmoset is
      similar to that of humans in that it is asymptomatic, long-lived and displays a
      very low level of circulating virus-infected cells. It differs from the human in
      lacking the characteristic antibody response to EBNA 1.

PMID- 9191940
TI  - Genetic content and preliminary transcriptional analysis of a representative
      region of murine gammaherpesvirus 68.
AB  - Murine gammaherpesvirus 68 (MHV-68) is a relatively recently discovered pathogen
      of wild rodents and provides a unique opportunity to explore in detail the
      interactions of a gammaherpesvirus with its natural host. It may also provide a
      much needed small animal model for human gammaherpesviruses. As a step in the
      detailed analysis of virus gene structure and expression we have sequenced over
      20 kb of the MHV-68 genome and mapped gene transcripts by Northern blot
      hybridization. The region we chose to analyse contains several conserved gene
      blocks as well as some less well conserved genes and allowed us to estimate the
      relationship of this virus to other herpesvirus family members. Of particular
      interest is the fact that none of the characteristic Epstein-Barr virus (EBV)
      genes is present at this genomic locus although MHV-68 does have one gene
      encoding a membrane glycoprotein, 9p150, which shows similarities to the major
      membrane glycoprotein of EBV. Our results further confirm that MHV-68 is a
      gammaherpesvirus marginally more closely related to a cluster of
      gammaherpesviruses including herpesvirus salmiri than to EBV. Northern analysis
      shows that the temporal regulation of expression is broadly similar to that of
      other herpesviruses in this region of the genome. We also show that like other
      gammaherpesviruses, MHV-68 splices its homologue of the EBV transcriptional
      activator gene BMRF1.

PMID- 9191941
TI  - Self-assembly of the JC virus major capsid protein, VP1, expressed in insect
      cells.
AB  - The major capsid protein of human polyomavirus JC virus, VP1, has been cloned
      into a baculovirus genome and expressed in insect cells. The VP1 protein was
      expressed in the cytoplasm and transported into the nucleus. It was then purified
      by a sucrose cushion and CsCI density gradient centrifugation to near
      homogeneity. Electron microscopy showed that isolated recombinant VP1 protein
      self-assembled into a capsid-like structure similar to the natural empty capsid.
      Both chelator (EDTA) and reducing agent (DTT) are required to disrupt the capsid
      structure into the pentameric capsomeres, as demonstrated by haemagglutination
      assay and electron microscopy. These results suggest that JC virus VP1 can be
      transported into the nucleus and self-assembled to form capsid-like particles
      without the involvement of the viral minor capsid proteins, VP2 and VP3. In
      addition, metal ions and disulphide bonds appear to be important in maintaining
      the integrity of the viral capsid structure.

PMID- 9191942
TI  - Interaction of human papillomavirus type 16 and adeno-associated virus type 2 co
      infecting human cervical epithelium.
AB  - Recently, we hypothesized that the tumour-suppressive, human helper-virus
      dependent, adeno-associated parvoviruses (AAV) may interfere with transforming
      functions of human papillomaviruses (HPV) in the development of cervical
      carcinoma. Here, we demonstrate that in cervical epithelium containing
      papillomavirus DNA, AAV DNA can be detected in a replication-competent form and
      that AAV proteins are expressed. In cultured cells containing integrated AAV-2
      DNA, transfection of HPV-16 DNA induced rescue of infectious AAV-2, revealing
      helper functions of HPV-16. Similarly, cotransfection of HPV-16 and AAV-2 DNAs
      into human epithelial cell lines led to replication of AAV-2, and, in
      keratinocytes, to a cytopathic effect. These data suggest an interaction of the
      two viruses, possibly influencing the development of HPV-related lesions.

PMID- 9191943
TI  - Assembly of adeno-associated virus type 2 capsids in vitro.
AB  - Capsid proteins VP1, VP2 and VP3 of adeno-associated virus type 2 (AAV-2) were
      separately expressed by recombinant baculoviruses, purified under denaturing
      conditions and renatured in the presence of 0.5 M arginine, followed by dialysis
      against buffers of physiological ionic strength. At a protein concentration of
      0.05 mg/ml, the three capsid proteins predominantly formed monomers and, to a
      lesser extent, oligomers, as determined by sedimentation analysis.
      Oligomerization increased at higher protein concentrations. The capsid protein
      oligomers consisted of globular, non-capsid-like structures, as detected by
      electron microscopy. Addition of a HeLa cell extract significantly stimulated
      oligomerization of the capsid proteins, probably due to interactions with HeLa
      cell proteins. Characterization of structures sedimenting around 60S by
      immunoprecipitation and electron microscopy showed that, in addition to other
      aggregates, empty capsid-like structures were formed in vitro. The identity of
      these structures as empty AAV capsids was verified by immunoelectron microscopy.
      Analysis of capsid formation in HeLa cells by transfection of VP expression
      constructs allowing separate expression of VP1, VP2 and VP3 showed that they were
      able to form capsids, although with a reduced efficiency as compared to VP
      proteins expressed from the wt cap gene. This finding suggests that the mutations
      introduced to allow separate capsid protein expression reduced the efficiency of
      capsid assembly in vivo and might also explain the reduced recovery of empty
      capsids employing the in vitro assembly procedure.

PMID- 9191944
TI  - Production of hepatitis B virus covalently closed circular DNA in transfected
      cells is independent of surface antigen synthesis.
AB  - Covalently closed circular DNA (cccDNA) is the first hepatitis B virus (HBV) DNA
      replicative intermediate formed from the genomic DNA and serves as the template
      for synthesis of viral mRNA and pregenomic RNA. It also appears to be produced by
      intracellular recycling of relaxed circular DNA intermediates. Here, we report
      that none of the forms of HBV surface antigen affect this intracellular recycling
      of HBV DNA. Elimination of the initiation codons for the large and middle surface
      proteins did not affect the detection of surface antigen in culture supernatants.
      In contrast, detection of surface antigen was eliminated by the removal of, or
      the introduction of two stop codons downstream of, the initiation codon of the
      small (major) surface antigen. None of the mutations affected the production, in
      transfected HepG2 cells, of HBV DNA replicative intermediates, including cccDNA.

PMID- 9191945
TI  - Hepatitis B virus X gene 1751 to 1764 mutations: implications for HBeAg status
      and disease.
AB  - A translational stop in the hepatitis B virus (HBV) precore codon 28 and specific
      changes in the core promoter region of the X gene have been suggested to
      influence the level of circulating HBeAg in patients. We analysed the core
      promoter region and precore sequences from 59 HBV strains (including 14 from the
      databank) of different genotypes and from patients with different HBeAg/anti-HBe
      patterns. The initiator and TATA elements for transcription of precore and
      pregenomic RNA were highly conserved. The majority of X gene deletions in the
      core promoter region would lead to translational frame-shifts and stops,
      truncating the C-terminal end of the X protein. We found significant associations
      between specific changes in core promoter positions 1762 to 1764, or in precore
      codon 28, and absence of circulating HBeAg. For the core promoter mutations
      alone, this association was related to the apparent degree of liver damage (as
      estimated by alanine aminotransferase levels) at the time of sampling. Mutations
      at nucleotides 1762 and/or 1764 were often accompanied by point mutations at
      positions 1751 to 1755. Since mutations at nucleotide positions 1762 and 1764
      have recently been shown by in vitro studies to suppress HBeAg production with a
      concomitant enhancement of virus production, disappearance of the HBeAg-positive
      phenotype associated with 1762 to 1764 mutations may thus have at least as much
      significance for the course of infection as HBeAg absence associated with precore
      codon 28 stop mutations. These observations are considered against a secondary
      structural model for the 3' end of HBV pregenomic RNA which also predicts
      enhancement of virus replication after mutation at positions 1762 and 1764.

PMID- 9191946
TI  - Reduced antigen production by hepatitis B virus harbouring nucleotide deletions
      in the overlapping X gene and precore-core promoter.
AB  - Hepatitis B virus (HBV) genomes with deletions in the precore-core (preC-C)
      promoter have been detected in HBV infections without serological markers. To
      address whether the mutations are responsible for the reduced production of virus
      antigenes, either an 8 bp (8d, position 1763 to 1770) or a 20 bp (20d, 1753 to
      1772) deletion was created in a wild-type (wt) HBV clone. Both mutations cause
      premature termination of the overlapping X ORF. When introduced into HepG2 cells,
      both mutants produced reduced amounts of HBsAg, HBcAg and HBeAg, but released the
      same or more virion-associated DNA compared with the wt. A co-transfection of the
      20d mutant with a small amount of intact X gene resulted in a 3-fold increase of
      HBcAg production compared to transfection with either the 20d or wt alone. When
      the promoter region was cloned into CAT plasmids, the 8d preC promoter showed
      weak activity and its initiation site was shifted 6 to 10 bp downstream. The preC
      promoter activity of 20d was not detectable by CAT ELISA and 5' RACE. The levels
      of C transcripts of both mutants were higher than that of the wt, and their start
      sites were not altered. Therefore, the deletions cause the reduction of HBsAg,
      HBcAg and HBeAg although the mutant viruses can still replicate in cultured
      cells. The reduction of HBeAg is due to both the reduced preC promoter activity
      and the defect in HBx. The reduction of HBcAg is due to the disrupted X gene,
      despite augmented C promoter activity.

PMID- 9191947
TI  - The hepatitis B virus MHBst167 protein is a pleiotropic transactivator mediating
      its effect via ubiquitous cellular transcription factors.
AB  - C-terminally truncated surface proteins of hepatitis B virus (HBV) are frequently
      translated from genomically integrated viral sequences. They may be relevant for
      hepatocarcinogenesis by stimulating gene expression. First, we examined the
      transactivating potential of middle hepatitis B surface protein truncated at
      amino acid (aa) position 167 (MHBst167) on the HBV regulatory element. In
      transient cotransfection assays using Chang liver or HepG2 cell lines and
      chloramphenicol acetyltransferase (CAT) reporter constructs only the HBV enhancer
      I, but no other HBV regulatory elements like the X promoter, the S1 or S2
      promoter or the enhancer II/core promoter could be stimulated by MHBst167. Since
      there is no evidence for a direct interaction of MHBst167 with DNA, we
      subsequently analysed whether cellular transcription factors were involved in
      mediating transactivation. This was tested both with isolated transcription
      factor-binding sites and in the natural context of viral and cellular promoter
      elements. Deletion analysis and electrophoretic mobility shift assays revealed
      that Sp1, AP1 and NF-kappa B can mediate transactivation by MHBst167. No
      involvement of CREB, NF1 or the liver-specific factor C/EBP was found. These data
      indicate that MHBst167 is a pleiotropic, non-liver-specific transactivator which
      exerts its effect via ubiquitous cellular transcription factors that are also
      involved in the regulation of expression of cellular genes relevant for
      proliferation and inflammation.

PMID- 9191948
TI  - Identification and functional analysis of a non-hr origin of DNA replication in
      the genome of Spodoptera exigua multicapsid nucleopolyhedrovirus.
AB  - The genome of Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV) was
      screened for the presence of putative origins of DNA replication (oris). Using a
      transient DNA replication assay, several fragments were identified that underwent
      SeMNPV-dependent DNA replication in Spodoptera frugiperda cells (Sf-AE-21).
      Preliminary sequence data revealed the presence of multiple copies of homologous
      repeats (hrs). Restriction fragment Xbal-F2 showed a distinct sequence
      reminiscent of Autographa californica and Orgyla pseudotsugata MNPV (AcMNPV and
      OpMNPV) non-hr oris. Deletion analysis of this fragment indicated that the
      essential sequences of this putative non-hr ori mapped within a region of 800 bp.
      Sequence analysis of this region showed a unique distribution of six different
      (im)-perfect palindromes, several polyadenylation motifs and the occurrence of
      multiple direct repeats. No sequence homology or similarities to other reported
      baculovirus oris were detected. The spatial and modular distribution of these
      motifs are similar to those of the non-hr oris of AcMNPV and OpMNPV. Comparison
      of baculovirus non-hr and consensus eukaryotic oris revealed no consensus ori but
      indicated that each of the non-hrs studied so far is unique. From the structural
      similarity, however, it was concluded that the SeMNPV Xbal-F2 ori represents a
      baculovirus non-hr type ori. In addition, evidence is provided that SeMNPV
      renders more specificity to baculovirus DNA replication than AcMNPV.

PMID- 9191949
TI  - Baculovirus transactivator IE1 is functional in mammalian cells.
AB  - IE1 of Autographa californica multicapsid nuclear polyhedrosis virus acts as a
      transactivator of several viral promoters in insect cells. Transient expression
      assays indicate that IE1 is involved in the activation of the early promoter he65
      in both insect TN-368 and mammalian BHK-21 cell lines. IE1 activation of the he65
      promoter was compared with IE1 activation of the early 39K promoter. In contrast
      to the he65 promoter, the 39K promoter was not inducible by IE1 in BHK-21 cells.

PMID- 9191951
TI  - 9-Benzyladenines: potent and selective cAMP phosphodiesterase inhibitors.

PMID- 9191950
TI  - Novel conformationally extended naphthalene-based inhibitors of
      farnesyltransferase.

PMID- 9191952
TI  - Substituted [(4-phenylpiperazinyl)-methyl]benzamides: selective dopamine D4
      agonists.

PMID- 9191953
TI  - Synthesis and biological evaluation of the enantiomers of the potent and
      selective A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbonyl)]
      xanthine.
AB  - The individual enantiomers 8 and 12 of the potent and highly selective racemic A1
      adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthine (ENX, 4)
      were synthesized utilizing asymmetric Diels-Alder cycloadditions for the
      construction of the norbornane moieties. The absolute configuration of 12 was
      determined by X-ray crystallography of the 4-bromobenzoate 14, which was derived
      from the bridged secondary alcohol 13. The latter was obtained from 12 by an acid
      catalyzed intramolecular rearrangement. The binding affinities of the enantiomers
      8 and 12 and the racemate 4 at guinea pig, rat, and cloned human A1- and A2a
      adenosine receptor subtypes were determined. The S-enantiomer 12 (CVT-124)
      appears to be one of the more potent and clearly the most A1-selective antagonist
      reported to date, with K1 values of 0.67 and 0.45 nM, respectively, at the rat
      and cloned human A1-receptors and with 1800-fold (rat) and 2400-fold (human)
      subtype selectivity. Both enantiomers, administered intravenously to saline
      loaded rats, induced diuresis via antagonism of renal A1-adenosine receptors.

PMID- 9191954
TI  - Non-peptide glycoprotein IIb/IIIa inhibitors. 17. Design and synthesis of orally
      active, long-acting non-peptide fibrinogen receptor antagonists.
AB  - The synthesis and pharmacological evaluation of 5 (L-738, 167), a potent,
      selective non-peptide fibrinogen receptor antagonist is reported. Compound 5
      inhibited the aggregation of human gel-filtered platelets with an IC50 value of 8
      nM and was found to be > 33000-fold less effective at inhibiting the attachment
      of human endothelial cells to fibrinogen, fibronectin, and vitronectin than it
      was at inhibiting platelet aggregation. Ex vivo platelet aggregation was
      inhibited by > 85% 24 h after the oral administration of 5 to dogs at 100
      micrograms/kg. The extended pharmacodynamic profile exhibited by 5 appears to be
      a consequence of its high-affinity binding to GPIIb/IIIa on circulating platelets
      and suggests that 5 is suitable for once-a-day dosing.

PMID- 9191955
TI  - Address and message sequences for the nociceptin receptor: a structure-activity
      study of nociceptin-(1-13)-peptide amide.
AB  - Nociceptin (NC) and some of its fragments as well as nociceptin-(1-13)-peptide
      amide [NC- (1-13)-NH2] and a series of its analogues were prepared and tested in
      the mouse vas deferens in an attempt to identify the sequences involved in the
      activation (message) and in the binding (address) of nociceptin to its receptor.
      The NC receptor that inhibits the electrically evoked twitches of the mouse vas
      deferens was demonstrated to be distinct from the delta opioid receptor, since
      naloxone and Dmt-Tic-OH (a selective delta opioid receptor antagonist) block the
      delta opioid receptor but have no effect on the nociceptin receptor. Results from
      structure-activity experiments suggest that (a) the entire sequence of NC may not
      be required for full biological activities, since NC(1-13)-NH2 is as active as
      NC; (b) fragments of NC have however to be amidated as in NC(1-13)-NH2 in order
      to be protected from degradation by proteases; (c) cationic residues (as Arg8,12,
      Lys9,13) appear to play a functional role, since their replacement with Ala in
      the sequence of NC(1-13)-NH2 leads to inactivity; (d) the N-terminal tetrapeptide
      Phe-Gly-Gly-Phe is essential for activity: its full length and flexibility appear
      to be required for NC receptor activation and/or occupation; (e) Phe4 and not
      Phe1 appears to be the residue involved in receptor activation, since the
      replacement of Phe1 with Leu has no effect, while that of Phe4 leads to
      inactivity. Results summarized in this paper indicate that the structural
      requirements of NC for occupation and activation of its receptor are different
      from that of opioids, particularly delta agonists.

PMID- 9191956
TI  - Discovery of a novel class of selective non-peptide antagonists for the human
      neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework.
AB  - A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor
      antagonists, featuring the 4-quinolinecarboxamide framework, has been designed
      based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33
      76, prompted by chemical modifications of the prototype 4, have been
      characterized by binding analysis using a membrane preparation of chinese hamster
      ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and
      clear structure-activity relationships (SARs) have been established. From SARs,
      (R)-N-[alpha-(methoxycarbonyl)benzyl]-2-phenylquinoline-4-carboxamide (65, SB
      218795, hNK-3-CHO binding Ki = 13 nM) emerged as one of the most potent compounds
      of this novel class. Selectivity studies versus the other neurokinin receptors
      (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3
      versus hNK-2 receptors (hNK-2-CHO binding Ki = 1221 nM) and over 7000-fold
      selective versus hNK-1 receptors (hNK-1-CHO binding Ki = > 100 microM). In vitro
      functional studies in rabbit isolated iris sphincter muscle preparation
      demonstrated that 65 is a competitive antagonist of the contractile response
      induced by the potent and selective NK-3 receptor agonist senktide with a Kb = 43
      nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor
      antagonist and a useful lead for further chemical optimization.

PMID- 9191957
TI  - Novel and selective partial agonists of 5-HT3 receptors. 2. Synthesis and
      biological evaluation of piperazinopyridopyrrolopyrazines,
      piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines.
AB  - In continuation of our previous work on piperazinopyrrolothienopyrazine
      derivatives, three series of piperazinopyridopyrrolopyrazines,
      piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines were
      prepared and evaluated as 5-HT3 receptor ligands. The chemical modifications
      performed within these new series led to structure-activity relationships
      regarding both high affinity and selectivity for the 5-HT3 receptors that are in
      agreement with those established previously for the pyrrolothienopyrazine series.
      The best compound (8a) obtained in these new series is in the picomolar range of
      affinity for 5-HT3 receptors with a selectivity higher than 10(6). Four of the
      high-affinity 5-HT3 ligands (8a, 15a,b, and 16d) were selected in both the
      pyridopyrrolopyrazine and the pyrroloquinoxaline series and were characterized in
      vitro and in vivo as agonists or partial agonists. Compound 8a was also evaluated
      in the light/dark test where it showed potential anxiolytic-like activity at very
      low doses per os.

PMID- 9191958
TI  - Tyrosine kinase inhibitors. 12. Synthesis and structure-activity relationships
      for 6-substituted 4-(phenylamino)pyrimido[5,4-d]pyrimidines designed as
      inhibitors of the epidermal growth factor receptor.
AB  - A series of 6-substituted 4-anilinopyrimido[5,4-d]pyrimidines has been prepared
      and shown to be potent inhibitors of the tyrosine kinase activity of the
      epidermal growth factor receptor (EGFR). These compounds are structurally related
      to the pyrido[3,2-d]- and pyrido[3,4-d]-pyrimidines previously shown to be EGFR
      inhibitors. Their structure-activity relationships (SAR) for inhibition of the
      isolated enzyme more closely resemble those of the [3,2-d] than the [3,4-d]
      pyridopyrimidine isomers. This suggests the requirement of an aza atom in the 7-
      but not the 5-position (i.e., a carbon atom in the 5-position) for the enhanced
      potency shown by 6-N-methylated derivatives in each series. X-ray crystal
      structures were determined for the three NHMe derivatives 2, 3, and 5c in the
      pyrido[9,2-d]-, pyrido[3,4-d]-, and pyrimido[5,4-d]-pyrimidine series,
      respectively. These show that a carbon rather than a nitrogen atom at the 5
      position leads to significant conformational changes in the molecule (a longer
      C5a-C4 bond and a 30 degrees out-of-plane rotation of the phenyl group), due to
      the requirement to relieve nonbonding interactions between the C5 and N9 protons.
      Pyrimido[5,4-d]pyrimidine analogues bearing bulky, weakly basic solubilizing side
      chains linked to the 6-position through a secondary amine generally retained
      potency both against the isolated enzyme and for inhibition of
      autophosphorylation of EGFR in intact A431 cells. This agrees with a recent
      binding model that suggests this general class of compounds binds to EGFR with
      the 6-position located in an area of comparative bulk tolerance at the entrance
      to the ATP-binding pocket. While these solubilized pyrimido[5,4-d]pyrimidine
      analogues were less potent than the NHMe derivative 5c in the isolated enzyme
      assay, some were considerably superior to 5c (and among the most potent ever
      reported) as inhibitors of EGFR autophosphorylation in cellular assays.

PMID- 9191959
TI  - Structure-cytoprotective activity relationship of simple molecules containing an
      alpha,beta-unsaturated carbonyl system.
AB  - In previous reports we attributed the cytoprotective activity of several
      sesquiterpene lactones to the presence of a nonhindered electrophilic acceptor in
      their structure. We suggested that the mechanism of protection would be, at least
      in part, mediated through a reaction between the electrophilic acceptor and the
      sulfhydryl-containing groups of the mucosa. We report here the gastric
      cytoprotective effect of simple molecules containing an alpha, beta-unsaturated
      carbonyl group. In the present paper, we undertake the study of molecular
      accessibility and molecular shape, in addition to conformational, electronic, and
      steric factors. Our results helped to establish two important facts connecting
      chemical structure with cytoprotective effect. Firstly, an adequate molecular
      accessibility appears to be necessary to produce the biological response, and
      secondly, the alpha,beta-unsaturated carbonyl system has to be included in a
      cyclic structure or, at least, in the proximity of a cyclic system.

PMID- 9191960
TI  - A technetium-99m SPECT imaging agent which targets the dopamine transporter in
      primate brain.
AB  - The dopamine transporter (DAT), located presynaptically on dopamine neurons,
      provides a marker for certain neurological diseases. In particular, the DAT is
      depleted in Parkinson's disease, and the extent of depletion correlates with the
      loss of dopamine. Herein we describe the design, synthesis, and biological
      evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which
      targets the dopamine transporter in striatum. We have demonstrated that the DAT
      can accommodate a chelating unit attached to the 8-amine function of a tropane
      skeleton. Further, we have demonstrated for the first time that a molecule can be
      designed to carry the radionuclide 99mTc across the blood-brain barrier in
      sufficient quantity to obtain in vivo images of the striatum in monkeys. This
      advance will undoubtedly lead to the design of new receptor and transporter
      mediated 99mTc agents which can label specific transporter and receptor targets
      in the central nervous system.

PMID- 9191961
TI  - Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
AB  - A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6
      (phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1
      activity. In particular, the influence of substitution of the terminal hydroxy
      group of the acyclic structure of HEPT and the structural rigidity of this side
      chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives
      were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the
      primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29
      were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with
      diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in
      which the N-1 side chain is rigidified by incorporation of an E-configured double
      bond, were obtained by palladium(0)-catalyzed coupling of several different 6
      (arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13,
      40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side
      chain, were found to be more potent than the known diphenyl-substituted HEPT
      analog BPT (2), two of them, 40c,d, being 10-fold more active.

PMID- 9191962
TI  - Simulation of protein-sugar interactions: a computational model of the complex
      between ganglioside GM1 and the heat-labile enterotoxin of Escherichia coli.
AB  - The cholera toxin from Vibrio cholerae (CT) and the 80% homologous heat-labile
      toxin of Escherichia coli (LT) are two well-known cases of sugar-binding
      proteins. The GM1:toxin complexes were chosen as test cases for the elaboration
      of a computational approach to the modeling of protein-saccharide interactions.
      The reliability of the method was evaluated on the LT:lactose complex. A model of
      this complex was built by performing a MC/EM conformational search of the sugar
      moiety within the binding pocket of LT, using the AMBER* force field and the
      GB/SA solvation model. The results are a reasonable reproduction of the reported
      X-ray structure of the complex. The same protocol was then applied to the LT:GM1
      complex. The calculations were performed on a substructure that includes the
      protein shell within 5 A from GM1, three water molecules solvating Glu-51
      carboxylate, and two water molecules at crystallographic sites 2 and 3. A
      satisfactory agreement was found with the recently published X-ray structure of
      the CT:GM1 complex. All the relevant interactions between the sugar and the
      residues involved in binding are well reproduced by the calculations. These
      results suggest that the substructure here identified can be taken as a realistic
      representation of the toxin binding surface and that the method presented in this
      paper can be used as a predictive tool in designing artificial LT (CT) binders
      and thus potential anticholera drugs.

PMID- 9191963
TI  - Neurotrophic 3,9-bis[(alkylthio)methyl]-and-bis(alkoxymethyl)-K-252a derivatives.
AB  - A series of 3,9 disubstituted [(alkylthio)methyl]- and (alkoxymethyl)-K-252a
      derivatives was synthesized with the aim of enhancing and separating the
      neurotrophic properties from the undesirable NGF (trk A kinase) and PKC
      inhibitory activities of K-252a. Data from this series reveal that substitution
      in the 3- and 9-positions of K-252a with these groups reduces trk A kinase
      inhibitory properties approximately 100- to > 500-fold while maintaining or in
      certain cases enhancing the neurotrophic activity. From this research, 3,9
      bis[(ethylthio)methyl]-K-252a (8) was identified as a potent and selective
      neurotrophic agent in vitro as measured by enhancement of choline
      acetyltransferase activity in embryonic rat spinal cord and basal forebrain
      cultures. Compound 8 was found to have weak kinase inhibitory activity for trk A,
      protein kinase C1 protein kinase A, and myosin light chain kinase. On the basis
      of the in vitro profile, 8 was evaluated in in vivo models suggestive of
      neurological diseases. Compound 8 was active in preventing degeneration of
      cholinergic neurons of the nucleus basalis magnocellularis (NBM) and reduced
      developmentally programmed cell death (PCD) of female rat spinal nucleus of the
      bulbocavernosus motoneurons and embryonic chick lumbar motoneurons.

PMID- 9191964
TI  - Novel prodrugs of cyanamide that inhibit aldehyde dehydrogenase in vivo.
AB  - S-Methylisothiourea (4), when administered to rats followed by a subsequent dose
      of ethanol, gave rise to a 119-fold increase in ethanol-derived blood
      acetaldehyde (AcH) levels-a consequence of the inhibition of hepatic aldehyde
      dehydrogenase (A1DH)-when compared to control animals not receiving 4. The
      corresponding O-methylisourea was totally inactive under the same conditions,
      suggesting that differential metabolism may be a factor in this dramatic
      difference between the pharmacological effects of O-methylisourea and 4 in vivo.
      The S-n-butyl- and S-isobutylisothioureas (8 and 9, respectively) at doses
      equimolar to that of 4 were nearly twice as effective in raising ethanol-derived
      blood AcH, while S-allylisothiourea (10) was slightly less active. However, blood
      ethanol levels of all experimental groups were indistinguishable from controls.
      Pretreatment of the animals with 1-benzylimidazole, a known inhibitor of the
      hepatic mixed function oxidases, followed sequentially by either 8, 9, or 10 plus
      ethanol, reduced blood AcH levels by 66-88%, suggesting that the latter compounds
      were being oxidatively metabolized to a common product that led to the inhibition
      of AcH metabolism. In support of this, when 8 was incubated in vitro with rat
      liver microsomes coupled to catalase and yeast A1DH, the requirement for
      microsomal activation for the inhibition of A1DH activity was clearly indicated.
      We suggest that S-oxidation is involved and that the S-oxides produced in vivo
      inhibited A1DH directly, or spontaneously released cyanamide, an inhibitor of
      A1DH. Indeed, incubation of 8 with rat liver microsomes and NADPH gave rise to
      cyanamide as metabolite, identified as its dansylated derivative. Cyanamide
      formation was minimal in the absence of coenzyme. Extending the side chain was
      detrimental, since S-benzylisothiourea (11) and S-n-hexadecylisothiourea (12)
      were toxic, the latter producing extensive necrosis of the liver and kidneys when
      administered to rats.

PMID- 9191965
TI  - Discovery and biological activity of orally active peptidyl trifluoromethyl
      ketone inhibitors of human neutrophil elastase.
AB  - Previously we had shown that tripeptidyl trifluoromethyl ketones (TFMKs)
      possessing an N-terminal diarylacylsulfonamide, such as ICI 200,880 and ICI
      200,355, displayed unparalleled protection against the lung damage induced by
      human neutrophil elastase (HNE) when the inhibitors were administered
      intratracheally. Since the diarylacylsulfonamides were designed specifically to
      afford a long residence time in the lung, it was not unexpected that inhibitors
      from this class of TFMKs were not active when administered orally. Upon
      evaluating a large number of peptidyl TFMKs possessing a variety of N-terminal
      groups, several compounds were identified which demonstrated oral activity.
      Compounds were evaluated for their oral activity by measuring their ability to
      inhibit the increase in lung weight relative to body weight (Lw/Bw), the increase
      in red blood cells, and the increase in white blood cells induced by
      intratracheally administered HNE (100 micrograms/hamster). A number of
      tripeptidyl trifluoromethyl ketones containing neutral N-terminal groups
      displayed good oral activity, while those containing basic, acidic, or polar
      groups did not. Compound 50, possessing an N-terminal 4-(CH3O)C6H4CO group, was
      particularly effective, reducing Lw/Bw by 77%, red cells by 89%, and white cells
      by 91% when dosed at 37.5 mg/kg orally. Thus, by modifying the N-terminal group
      of tripeptidyl TFMKs, inhibitors can be designed which are effective in vivo when
      administered either orally or intratracheally.

PMID- 9191966
TI  - Structural studies on bioactive compounds. 28. Selective activity of triazenyl
      substituted pyrimethamine derivatives against Pneumocystis carinii dihydrofolate
      reductase.
AB  - Triazenyl-substituted pyrimethamine derivatives 10a-s have been prepared by
      coupling diazotized 2,4-diamino-5-(3-amino-4-chlorophenyl)-6-ethyl pyrimidine
      (1c) with a series of secondary amines in aqueous sodium carbonate solution. The
      triazenes which are stable and poorly soluble as free bases form more soluble,
      but unstable, salts with alkanesulfonic acids. The lead dimethyltriazene 2,4
      diamino-5[4-chloro-3-(3,3-dimethyltriazen-1-yl)phenyl]-6-et hylpyrimidine (4a)
      forms a crystalline ethanesulfonic acid salt (solvated with 2-propanol), which is
      protonated at the pyrimidine N-1 position, as determined by X-ray
      crystallography. The ability of these new triazenes to inhibit Pneumocystis
      carinii dihydrofolate reductase in vitro has been compared to that of triazene
      4a. The most potent and selective compound, 2,4-diamino-5-[3-[3-[2
      (acetyloxy)ethyl]-3-benzyltriazen-1-y l]-4- chlorophenyl]-6-ethylpyrimidine
      (14a), has an IC50 value of 0.17 microM against the microbial enzyme and
      potentially useful selectivity (rat liver IC50/P. carinii IC50 = 114).

PMID- 9191967
TI  - Design and synthesis of potent antitumor 5,4'-diaminoflavone derivatives based on
      metabolic considerations.
AB  - Recently, we reported that 5,4'-diaminoflavone (1) exhibits potent and specific
      growth-inhibitory activity against the estrogen receptor (ER)-positive human
      breast cancer cell line MCF-7. However, when compound 1 was incubated with S-9
      mix, its metabolites were observed. Moreover, addition of S-9 mix to the medium
      caused the drastic decrease in activity of compound 1. Since the 6-, 8-, and 3'
      positions were considered to be metabolized oxidatively in vivo from MO
      calculations, a series of 5,4'-diaminoflavone derivatives substituted at such
      putative metabolic positions with various functional groups were synthesized
      aiming at the metabolically stable derivatives. Among them, 5,4'-diamino-6,8,3'
      trifluoroflavone (14d) exhibited strong growth-inhibitory activity against MCF-7
      cells even in the presence of S-9 mix. Moreover, orally administered compound 14d
      completely suppressed the growth of MCF-7 inoculated into nude mice, and the
      effect was more potent than that of compound 1. In addition to ER-positive breast
      cancer cells, compound 14d exhibited growth-inhibitory activity against a panel
      of human cancer cell lines including a part of ER-negative breast, endometrial,
      ovarian, and liver cancers. From these results, fluorine introduction to the
      putative metabolic positions of compound 1 was elucidated to be effective in the
      enhancement of the in vivo antitumor activity, probably due to the block of the
      metabolic deactivation.

PMID- 9191968
TI  - Substituted N-phenylisothioureas: potent inhibitors of human nitric oxide
      synthase with neuronal isoform selectivity.
AB  - S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both
      the human constitutive and inducible isoforms of nitric oxide synthase. A series
      of substituted N-phenylisothiourea analogues was synthesized to investigate the
      structure-activity relationship of this class of inhibitor. Each analogue was
      evaluated for human isoform selectivity. One analogue, S-ethyl N-[4
      (trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold
      selectivity for the neuronal isoform versus the inducible and endothelial derived
      constitutive isoforms, respectively. Studies have shown the substituted N
      phenylisothiourea 39 binds competitively with L-arginine.

PMID- 9191969
TI  - Dual inhibition of human leukocyte elastase and lipid peroxidation: in vitro and
      in vivo activities of azabicyclo[2.2.2]octane and perhydroindole derivatives.
AB  - A series of potent and selective human leukocyte elastase (HLE) inhibitors of the
      Val-Pro-Val type has been developed. Initially, the central proline residue was
      replaced by nonnatural amino acids Phi ((2S,3aS,7aS)-perhydroindole-2-carboxylic
      acid) and Abo ((3S)-2-azabicyclo-[2.2.2]octane-3-carboxylic acid), and secondly
      several groups able to confer antioxidant properties to the molecule were
      introduced at the lipophilic N-terminal side chain. When compared to reference
      inhibitors, in vitro HLE inhibitory potency was maintained (10-100 nM) both with
      compounds containing the antioxidant moiety at the end of the N-terminal side
      chain and with compounds in which the N-terminal valine of the tripeptidic
      sequence had been replaced by a epsilon-substituted lysine. The lipidic
      peroxidation inhibitory potency of this series of inhibitors was found to be
      similar to that of the reference antioxidant compounds (around 1 microM).
      Moreover, HLE-induced hemorrhage in the hamster lung was effectively prevented
      (40-60% at 15 micrograms/kg) by most of the inhibitors tested when administered
      intratracheally 3 h before instillation of elastase. Among the most active
      analogs, compounds 11a,c,g were still active when administered 18 h before
      elastase. Interestingly, compound 14a was able to prevent HLE-mediated lung
      damage when administered 72 h prior to enzymatic challenge, indicating
      exceptional stability and retention in the lung. Finally, in a 14-day chronic
      model of emphysema in the hamster, 14a significantly conserved alveolar spaces, a
      marker of lung tissue destruction, and was more potent than reference inhibitor
      ICI 200 880. This indicates that addition of peroxidation inhibitory properties
      to an HLE inhibitor can provide a powerful in vivo inhibitor of pulmonary tissue
      destruction.

PMID- 9191970
TI  - Structure-activity relationships for acridine-substituted analogues of the mixed
      topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.
AB  - The mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4
      carboxamide (DACA) is currently in clinical trial as an anticancer drug. A series
      of acridine-substituted analogues were prepared, using a new synthetic route to
      substituted acridine-4-carboxylic acids (conversion of substituted diphenylamine
      diacid monoesters to the corresponding aldehydes and mild acid-catalyzed ring
      closure to form the acridines directly). The analogues were evaluated in a panel
      of cell lines which included wild-type (JLC) and mutant (JLA and JLD) forms of
      the human Jurkat leukemia line. The latter mutant lines are resistant to
      topoisomerase II targeted agents due to lower levels of the enzyme. Structure
      activity studies suggest that the electronic properties of the substituents do
      not markedly affect cytotoxicity, but steric bulk is important, with larger
      groups leading to loss of activity. The compounds fell broadly into two
      categories. The majority had cytotoxicities similar to (or lower than) that of
      DACA itself and were equitoxic in all the Jurkat lines, suggesting a relatively
      greater effect on topoisomerase I compared with topoisomerase II. Most of the 5
      substituted derivatives and the 7-Ph compound were more cytotoxic than DACA, but
      were less effective against JLA and JLD cell lines than in the wild-type JLC,
      suggesting a mode of cytotoxicity largely mediated by effects on topoisomerase
      II. Both DACA and selected acridine-substituted analogues were active in the
      relatively refractory subcutaneous colon 38 tumor model in vivo.

PMID- 9191972
TI  - Toward a novel metal-based chemotherapy against tropical diseases. 3. Synthesis
      and antimalarial activity in vitro and in vivo of the new gold-chloroquine
      complex [Au(PPh3)(CQ)]PF6.

PMID- 9191971
TI  - Synthesis and biological activities of conformationally restricted, tricyclic
      nonclassical antifolates as inhibitors of dihydrofolate reductases.
AB  - Seven novel tricyclic pyrimido[4,5-c][2,7]naphthyridones 5-8 and the
      corresponding naphthyridines 9-11 were synthesized as conformationally restricted
      inhibitors of dihydrofolate reductase (DHFR) and as antitumor and/or
      antiinfectious agents. The analogues were designed to orient the side chain
      trimethoxyphenyl group in different conformationally defined positions in order
      to explore the effect of the side chain orientation on binding affinity and
      selectivity for DHFR from various species. The semirigid orientations were
      achieved by bridging the C5 and N10 of compound 12 with a N-ethyl bridge and by
      variation of the position of double bonds in rings B and C as well as
      substitution at the 2',6'-positions of the phenyl ring. The synthesis of
      compounds 5-11 were accomplished by cyclocondensation of the appropriate keto
      ester (as the biselectrophile) with 2,4,6-triaminopyrimidine to afford the lactam
      5. The dehydrolactams 6 and 7 were prepared by air oxidation and PtO2-catalyzed
      dehydrogenation of 7, respectively. The dichloro dehydro lactam 8 was obtained by
      refluxing lactam 5 and/or 6 in POCl3 or a mixture of POCl3/PCl5. Compounds 9-11
      were obtained by two methods, direct borane reduction of lactam 5 or 6 or
      thiation of the dipivoylated lactam 15 followed by reductive dethiation.
      Compounds 9-11 were interconverted by air oxidation or PtO2-catalyzed
      reduction/oxidation, respectively. The compounds were evaluated as inhibitors of
      DHFR from Pneumocystis carinii (pc) and Toxoplasma gondii (tg) with rat liver
      (rl) serving as the reference mammalian enzyme. In the lactam series 5-8, the
      most unsaturated analogue 7 showed an IC50 of 86 nM against rlDHFR, almost 100
      fold more active than 5 and 3-fold more active than 6. The 2',6'-dichloro dehydro
      lactam 8 was less active than the corresponding dehydro lactam 6 against rlDHFR.
      In the naphthyridine series 9-11, the dehydro analogue 10 was more active than 9
      against rlDHFR. The fully reduced analogue 11 (as a mixture of cis and trans
      isomers) was the most active in the naphthyridine series. The analogues were, in
      general, more inhibitory against rlDHFR than against pcDHFR, or tgDHFR, and thus
      lacked selectivity. In addition, they were less potent than the bicyclic
      compounds trimetrexate 3 (TMQ) and piritrixim 4 (PTX).

PMID- 9191973
TI  - Glucocorticoids induce corticosteroid-binding globulin biosynthesis by immature
      mouse liver and kidney.
AB  - Marked changes in mouse corticosteroid-binding globulin (CBG) gene expression in
      the liver and kidney occur postnatally. To study the influence of glucocorticoids
      on the initiation of mouse CBG biosynthesis in these tissues during the first two
      weeks after birth, we administered dexamethasone (0.5 microgram/g body wt/day) to
      4- and 11-day-old pups for three days. This resulted in higher serum CBG and
      hepatic CBG mRNA levels in animals, irrespective of their ages. Higher relative
      amounts of CBG mRNA in the kidneys of 14-day-old pups after three days of
      dexamethasone treatment co-incided with higher amounts of intact and
      proteolytically cleaved CGB in their urine, and both are indicative of increased
      CGB production by the developing renal tubules. When an additional group of 11
      day-old pups (n = 4) was treated with 0.25 microgram dexamethasone/g body weight
      per day for five days, this also resulted in significantly higher levels of serum
      CBG (P < 0.01), hepatic CBG mRNA (P < 0.01) and renal CBG mRNA (P < 0.05),
      compared to littermates treated with the oil vehicle alone. In contrast, serum
      CBG levels progressively decreased in adult female mice during five days of
      treatment with 0.5 microgram dexamethasone/g body weight per day. Taken together,
      these data indicate that glucocorticoids induce murine CBG gene expression in the
      immature liver and kidney, and support the concept that the effects of
      glucocorticoids on CBG gene expression are developmentally stage-specific.

PMID- 9191974
TI  - Developmental response by Leydig cells to acidic and basic fibroblast growth
      factor.
AB  - The present study examines the effects of acidic (FGF-1) and basic (FGF-2)
      fibroblast growth factors on Leydig cell steroidogenesis by cells from 5-, 21-
      and 90-day-old rats. These ages represent three distinct time points in Leydig
      cell development: fetal Leydig cells (day 5), immature Leydig cells (day 21) and
      adult Leydig cells (day 90). The results demonstrate that the actions of the two
      growth factors on steroidogenesis are developmentally regulated, and require the
      presence of heparan sulphate proteoglycans (HSPG). FGF-1 and FGF-2 both had
      stimulatory effects on basal, but not maximally LH-stimulated, testosterone
      production by fetal Leydig cells, and both growth factors stimulated basal 5
      alpha-androstane-3 alpha, 17 beta-diol production by immature Leydig cells. These
      effects were mediated by heparan sulphate-proteoglycans (HSPG), as they were
      blocked by the addition of protamine sulphate and sodium chlorate. FGF-1 and FGF
      2 had no effect on basal testosterone production by adult Leydig cells, however,
      FGF-1 alone inhibited LH-stimulated testosterone production by adult Leydig cells
      in a dose-dependent manner. These data demonstrate that the effects of FGF-1 and
      FGF-2 are dependent on the specific stage of Leydig cell differentiation and
      development and may vary accordingly. Furthermore, although FGF-1 and FGF-2 are
      closely related structurally, a different effect of these two growth factors can
      be observed on the same type of Leydig cells. The data therefore suggest that
      these growth factors may have different but specific roles in the regulation of
      Leydig cell steroidogenesis, at different stages of development.

PMID- 9191975
TI  - In vitro binding of vitamin D receptor occupied by 24R,25-dihydroxyvitamin D3 to
      vitamin D responsive element of human osteocalcin gene.
AB  - We previously reported that 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] activates
      the human osteocalcin gene (hOC) through vitamin D receptor (VDR) and vitamin D
      responsive element (VDRE) in the same manner as 1 alpha,25-dihydroxyvitamin D3 [1
      alpha,25(OH)2 D3] [17]. In the present study, the interaction of 24R,25(OH)2D3
      liganded VDR [24R,25(OH)2D3-VDR] with the hOC VDRE in vitro was investigated. The
      electrophoretic mobility shift assay (EMSA) revealed that the binding of
      24R,25(OH)2D3-liganded VDR to the hOC VDRE was weak, even at concentrations of
      24R,25(OH)2D3 10(5)-fold higher than 1 alpha,25(OH)2D3. The effect of the nuclear
      accessory factor (NAF), which is required for the high affinity interaction of
      the VDR to the VDRE, on the binding of the 24R,25(OH)2D3-VDR to the VDRE was
      studied using hOC VDRE affinity column chromatographic assays. In the absence of
      NAF, the 24R,25(OH)2D3-VDR associated weakly with the VDRE compared to the 1
      alpha,25(OH)2D3-liganded VDR [1 alpha,25(OH)2D3-VDR], whereas the NAF enhanced
      the binding of the 24R,25(OH)2D3-VDR for the VDRE. In the absence of the hOC
      VDRE, the binding affinity of the 24R,25(OH)2D3-VDR for the NAF was weaker than
      that of 1 alpha,25(OH)2D3-VDR. These results suggest that the weak interaction of
      the 24R,25(OH)2D3-VDR with both NAF and hOC VDRE is responsible for the weak
      binding of the 24R,25(OH)2D3-VDR to the VDRE detected in EMSA. In terms of VDR
      function, 24R,25(OH)2D3 was more potent in transactivation than in vitro binding.

PMID- 9191976
TI  - Calmidazolium and other imidazole compounds affect steroidogenesis in Y1 cells:
      lack of involvement of the peripheral-type benzodiazepine receptor.
AB  - Calmidazolium potently stimulated steroidogenesis in a mouse adrenocortical Y1
      cell line, in a Ca(2+)-independent manner, an effect similar to that reported by
      Choi and Cooke [1] for rat primary adrenocortical and Leydig cells. Calmidazolium
      analogues, econazole and miconazole, were shown to inhibit both this
      calmidazolium-stimulated rate and the endogenous rate of steroidogenesis. In
      determining the mechanism by which imidazole compounds affect steroidogenesis,
      they were found not to act directly on the mitochondrial Cyt P-450scc enzyme,
      making it likely that they act instead on the intramitochondrial transport of
      cholesterol. Using competition binding studies, calmidazolium, econazole and
      miconazole were subsequently identified as novel ligands for the peripheral-type
      benzodiazepine receptor (PBR). Econazole and miconazole were found to inhibit
      stimulation by PK 11195 (a specific PBR ligand) of steroidogenesis, whereas
      treatment of the cells with calmidazolium and PK 11195 at the same time resulted
      in an additive stimulatory effect on steroidogenesis. These results suggest that
      the effects of these substituted imidazoles on steroidogenesis in Y1 cells is not
      mediated through their interaction with the PBR.

PMID- 9191977
TI  - RU486 is a potent inhibitor of aromatase induction in human breast adipose tissue
      stromal cells.
AB  - Aromatization of circulating androgens in adipose tissue is a major source of
      estrogens in postmenopausal women. As part of our efforts to elucidate the
      mechanism of aromatase induction in human breast adipose tissue, we tested the
      effects of the antiglucocorticoid and antiprogestin, RU486, on aromatase
      induction in primary cultures of adipose tissue stromal cells in a serum-free
      system devoid of phenol-red. Under these conditions 1 microM cortisol alone
      induces low levels of aromatase activity within one day, whereas platelet-derived
      growth factor BB (PDGF) potentiates this effect two- to three-fold. The well
      known strong inductive effect of dibutyryl-cAMP (db-cAMP) is also augmented by
      cortisol, but is inhibited by PDGF in the absence of cortisol. RU486 completely
      prevented aromatase induction by cortisol and PDGF. Induction by db-cAMP in the
      presence and absence of cortisol was significantly inhibited by RU486. Even lower
      activities were measured when RU486 was added to cells stimulated with PDGF and
      db-cAMP in the absence or presence of cortisol. Similar results were obtained
      after prolonged incubation. The inhibitory effects of RU486 are dose dependent,
      less than 1 microM completely blocking the effects of cortisol, whereas 10 microM
      are needed to block db-cAMP induction. RU486 does not affect cell number,
      cellular protein, viability or house-keeping enzymes such as lactate
      dehydrogenase (LDH), and therefore seems to act specifically. The time course of
      RU486 action on the db-cAMP induction of aromatase indicates that it acts via a
      newly synthetized mediator or target in stromal cells. These results suggest that
      all known inducers of aromatase in adipose tissue depend upon the action of
      signalling molecules (probably members of the nuclear receptor superfamily) which
      can be blocked by RU486. The inhibitory action of PDGF seems to be independent of
      steroid hormone action, as seems some basal activity induced by db-cAMP. In
      conclusion, this in vitro study suggests that RU486 might be a useful tool for
      the therapy of estrogen-dependent tumours through its inhibition of aromatase
      induction.

PMID- 9191978
TI  - Glucocorticoid receptors and actions in the spinal cord of the Wobbler mouse, a
      model for neurodegenerative diseases.
AB  - We have studied glucocorticoid receptors (GR) and actions in the spinal cord of
      the Wobbler mouse, a model for amyotrophic lateral sclerosis and infantile spinal
      muscular atrophy. Basal and stress levels of circulating corticosterone (CORT)
      were increased in Wobbler mice. Single point binding assays showed that cytosolic
      type II GR in the spinal cord of Wobbler mice of both sexes were slightly reduced
      compared with normal littermates. Saturation analysis further demonstrated a non
      significant reduction in Bmax with increased Kd. In the hippocampus, however, we
      found down-regulation of GR, a probable response to increased CORT levels. We
      also found that the basal activity of ornithine decarboxylase (ODC), a rate
      limiting enzyme of polyamine biosynthesis, was higher in Wobbler mice than in
      control animals. Both groups showed a two-fold stimulation of ODC activity after
      treatment with dexamethasone (DEX). Additionally, Wobbler mice presented with an
      intense proliferation of astrocytes immunoreactive (ir) for glial fibrillary
      acidic protein (GFAP) in grey and white matter of the spinal cord. The enhanced
      GFAP-ir was attenuated after four days of treatment with a corticosterone (CORT)
      pellet implant, producing a pharmacological increase in peripheral circulating
      CORT. Taking into consideration the content of GR and the changes in ODC activity
      and GFAP-ir brought about by glucocorticoids, we suggest that Wobbler mice are
      hormone responsive. Further elucidation of glucocorticoid effects in this model
      may be relevant for understanding the possible use of hormones in human
      neurodegenerative diseases.

PMID- 9191979
TI  - Enhancement of potassium-, and angiotensin II-stimulated aldosterone production
      by the calcium chelator EGTA in bovine adrenal glomerulosa cells in vitro.
AB  - The present study was designed to assess the effect of the calcium chelator EGTA
      (ethylenglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1.0 mM) on
      potassium (8 mM)- and angiotensin II (AII; 10 nM)-stimulated aldosterone
      production in bovine adrenal glomerulosa cells in vitro. The combined
      administration of EGTA and potassium, or of EGTA and AII, yielded a significant
      increase in the levels of aldosterone production. The net increment in
      aldosterone production after the combined administration of EGTA and potassium,
      or that after the combined administration of EGTA and AII was also significantly
      higher than the sum of that evoked by EGTA and potassium alone, or the sum of
      that evoked by EGTA and AII alone, respectively. At similar concentrations of
      extracellular ionized calcium ([Ca2+]out) or magnesium, the levels of agonist
      stimulated aldosterone production were markedly elevated by the administration of
      EGTA. These results indicate that lowering [Ca2+]out concentrations with EGTA
      enhances potassium- and AII-stimulated aldosterone production in bovine adrenal
      glomerulosa cells in vitro. This enhancement may be predominantly due to another
      effect of EGTA, in addition to the stimulation of calcium entry into the cells.

PMID- 9191980
TI  - Epidermal growth factor and transforming growth factor alpha mRNA expression in
      human breast cancer biopsies; analysis in relation to estradiol, progesterone and
      EGF receptor content.
AB  - Among the peptide growth factors active in breast glandular cell proliferation
      epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha)
      are thought to play a major role in tumour development. They operate through
      binding to and activation of a common membrane receptor, defined as EGF-R. Their
      production is modulated by hormones and local growth factors. After it was shown
      by previous investigation in this laboratory that EGF-R could be detected in 90%
      of the tumours, but was masked by endogenous ligand in 36% of them, the question
      was raised as to the level of the ligand's expression in tumour tissue biopsies.
      Therefore, we investigated the expression of EGF and TGF alpha mRNA in 146 breast
      cancer biopsies by slot blot analysis using specific 32P-labelled probes. The
      data were correlated with sex steroids and EGF receptor content. Our results
      showed that EGF and TGF alpha coexisted in all tumour samples, and that their
      level of mRNA expression was similar in half of the tumours. Northern blot and
      polymerase chain reaction (PCR) analysis validated these findings. A significant
      direct correlation was found between the level of TGF alpha/EGF mRNA expression
      and the ER/progesterone receptor (PGR) content. TGF alpha and EGF mRNA levels
      were significantly higher in ER+ (P = 0.0015 and P = 0.0001, respectively) and in
      PGR+ tumours (P < 0.005 and P = 0.0001) than in their negative counterparts.
      Moreover, TGF alpha mRNA expression negatively correlated with the number of EGF
      R binding sites measured by the standard method (P = 0.02), and it was
      significantly related to the number of sites occupied by endogenous ligand. In
      conclusion, it was shown that TGF alpha and EGF mRNA were coexpressed in all the
      tumour biopsies tested and that their level was higher in the hormone receptor
      positive than in negative samples. The correlation between the presence of ER/PGR
      sites, high level of TGF alpha/EGF mRNA and EGF-R occupancy by endogenous ligand
      is in favour of ER mediated control of TGF alpha and EGF production.

PMID- 9191981
TI  - High-affinity binding of corticosterone to mammalian neuronal membranes: possible
      role of corticosteroid binding globulin.
AB  - The signal transduction mechanisms mediating rapid steroid actions are poorly
      understood. To characterize corticosteroid interaction with neuronal membranes in
      a species with rapid behavioral responses to corticosterone, we examined
      [3H]corticosterone binding to membranes prepared from prairie vole brains. At 22
      degrees C, the rates of association and dissociation of [3H]corticosterone with
      well-washed synaptosomal membranes were very rapid. Specific binding was
      characterized by high affinity (Kd = 6.01 nM) and low density (Bmax = 63.1
      fmol/mg protein). The binding sites were highly specific for naturally occurring
      glucocorticoids and the density of binding sites appeared to vary by
      neuroanatomical region. Unlike most G-protein-coupled receptors, the high
      affinity binding of [3H]corticosterone to vole brain membranes was unaffected by
      the addition of Mg2+ or guanyl nucleotides. Surprisingly, saline perfusion of
      vole brains before tissue homogenization greatly reduced high-affinity binding.
      In addition, the affinity and specificity of corticosteroid binding sites were
      similar in vole neuronal membranes and vole plasma. These data suggest that
      corticosteroid binding globulins may facilitate [3H]corticosterone binding to
      neuronal membranes. However, the addition of blood to perfused brains before
      homogenization did not restore high-affinity binding, so the role of plasma
      binding globulins is unclear. Whether these binding phenomena represent a
      technical artifact or a regulatory mechanism for corticosteroid action has yet to
      be determined.

PMID- 9191982
TI  - Androgen stimulation of lacrimal gland function in mouse models of Sjogren's
      syndrome.
AB  - Sjogren's syndrome, an autoimmune disease that occurs primarily in women, causes
      extensive inflammation and significant dysfunction in the lacrimal gland, and is
      one of the leading causes of dry eye syndromes throughout the world. Recently,
      our research has shown that androgen treatment causes a significant suppression
      of the immunopathological lesions in lacrimal tissues of female mouse models
      (MRL/Mp-lpr/lpr [MRL/lpr] and NZB/NZW F1 [F1]) of Sjogren's syndrome. To extend
      these findings, the objective of the present study was to determine whether this
      androgen-induced anti-inflammatory action may be paralleled by an increase in the
      functional activity of lacrimal glands in these autoimmune mice. Towards this
      end, we measured the tear levels of immunoglobulin A (IgA), which originates from
      lacrimal tissue and whose concentration is known to be diminished in mucosal
      sites in Sjogren's syndrome. For comparative purposes, we also evaluated whether
      the administration of other steroid hormones or immunosuppressive agents might
      duplicate possible androgen effects on the secretory function of lacrimal tissue.
      Female MRL/lpr and F1, as well as non-autoimmune BALB/c, mice were treated with
      vehicle, steroids or immunosuppressive compounds for 17 to 54 days after the
      onset of disease. Lacrimal glands, tears and sera were collected immediately
      before (pretreatment), or after, therapy and processed for the analysis of either
      tear IgA (enzyme-linked immunosorbent assay; ELISA) and protein content or the
      magnitude of lymphocyte infiltration (computer-assisted image analysis). Our
      findings demonstrated that testosterone treatment stimulated a significant
      increase in the concentration and total amount of tear IgA, as well as tear
      protein, compared to levels in pretreatment or placebo controls. This hormone
      action was reproduced by exposure to a diverse array of "anabolic" and
      "androgenic" androgen analogues, but not by treatment with estradiol, danazol,
      cyclosporine A, dexamethasone or cyclophosphamide. In contrast, only
      dexamethasone increased serum IgA concentrations. Of particular interest is the
      fact that the androgen control of IgA output by the lacrimal gland appeared to be
      independent of this steroid's suppression of lymphocyte infiltration in lacrimal
      tissue. Overall, these results show that androgen therapy enhances the functional
      activity of the lacrimal gland in mouse models of Sjogren's syndrome.

PMID- 9191983
TI  - 11 beta-Hydroxysteroid dehydrogenase 1 activity and gene expression in human
      adipose stromal cells: effect on aromatase activity.
AB  - The biological activity of glucocorticoids in target tissues can be influenced by
      locally produced 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the enzyme
      responsible for the interconversion of cortisol and its inactive metabolite
      cortisone. In human adipose stromal cells, glucocorticoids are potent stimulators
      of the conversion of androgens to estrogens (aromatase activity). The present
      study was designed to determine whether 11 beta-HSD activity was present in human
      adipose stromal cells, and if changes in the activity of this enzyme could
      influence aromatase activity. 11 beta-HSD activity was determined by a
      radiometric conversion assay in breast adipose tissue from six patients. It was
      found that both dehydrogenase (cortisol to cortisone) and reductase (cortisone to
      cortisol) activities were present in all six subjects, and the reductase activity
      was always predominant. Carbenoxolone (CBX), a potent inhibitor of 11 beta-HSD,
      added to the culture medium at 50 and 200 microM, resulted in 39 +/- 4% and 85 +/
      1% inhibition, respectively, of both reductase and dehydrogenase activity of 11
      beta-HSD. To determine whether alterations in 11 beta-HSD could influence
      aromatase activity, the effect of CBX (200 microM) on cortisol- and cortisone
      induced changes in the conversion of androstenedione to estrone was examined. CBX
      prevented the stimulatory effect of cortisone and minimally potentiated the
      stimulatory effect of cortisol on aromatase activity, reflecting an inhibition of
      the local activation of cortisone and the local metabolism of cortisol,
      respectively. In order to determine whether the product of the 11 beta-HSD 1 gene
      was responsible for the observed 11 beta-HSD activity, total RNA extracts from
      these cells were subjected to Northern blot analysis using human 11 beta-HSD 1
      cDNA as the probe. A single 1.8 11 beta-HSD 1 transcript was detected, and its
      abundance was reduced by CBX. No 11 beta-HSD 2 mRNA was detected. The present
      results demonstrate that the 11 beta-HSD 1 gene is expressed and functional in
      human breast adipose stromal cells and that changes in 11 beta-HSD 1 activity
      result in alterations in aromatase activity.

PMID- 9191984
TI  - Isotope effect in the binding of tritium and 14C-labelled cortisol to
      corticosteroid-binding-globulin in serum.
AB  - We have determined the free cortisol concentration in serum using either the
      Amicon MPS-1 ultrafiltration-centrifugation method (I) or equilibrium dialysis
      (II). If procedure I was used we found that [1,2,6,7-3H]-, and [4-14C]cortisol
      had a lower affinity than unlabelled cortisol for corticosteroid binding globulin
      (CBG). The binding affinity (Ka) to three separate CBG-containing samples was 8
      18 times lower for [1,2,6,7-3H]cortisol and 30-90 times lower for [4
      14C]cortisol, when compared with that of unlabelled cortisol. This difference in
      affinity to CBG was not observed if method II was used for the free cortisol
      determinations. The observed isotope effect in method I is not caused by
      unspecific binding to material such as the Amicon MPS-1 chamber or to impurities
      in the tracer. We suggest that the centrifugation step during ultrafiltration
      changed the conformation of CBG, thereby reducing its affinity for labelled
      cortisol. It is concluded that incorrect results will be obtained if
      radiolabelled is cortisol used for determining the free cortisol content of
      plasma with the Amicon MPS-1 device.

PMID- 9191986
TI  - Neuro-immune pathobiology of infectious enteric disease.
AB  - Recent knowledge of neuro-endocrine-immune communication in the intestinal mucosa
      has provided a new paradigm for the pathophysiology of diarrheal disease that
      will significantly alter and advance therapeutic strategies. Mast cells,
      enteroendocrine cells and phagocytes are the proximate mediators of signalling
      cascades activated by parasitic nematodes and food allergens, enterotoxigenic
      bacteria, and at least some of the invasive pathogens, respectively. These
      proximate, trigger cells give rise to products that affect epithelial function
      directly, or indirectly through stimulation of prostaglandin production by
      mesenchymal cells, and enteric nerve stimulation, which can markedly amplify the
      initial stimulus. The enteric nervous system in fact may mediate the majority of
      the secretory response induced by enterotoxins or phagocytes. The signalling
      network mediated by cells in the lamina propria provides new points of control
      for pharmacological therapy.

PMID- 9191985
TI  - Comparative histopathology of intestinal infections.
AB  - Intestinal infections are characterized by a range of histologic changes. Some
      examples (moving progressively deeper into the tissue from the intestinal lumen)
      are: 1) Enterotoxigenic E. coli infections are characterized by layers of E. coli
      adherent to villous epithelium, usually with little or no apparent structural
      damage to the mucosa. 2) The term enteropathogenic E. coli infection designates a
      disease characterized by E. coli attached intimately to the epithelial cell
      surface membrane with effacement of brush border microvilli. 3) Rotavirus
      infections are characterized by destruction of villous epithelial cells.
      Parvovirus infections are characterized by destruction of crypt epithelial cells.
      4) Some intracellular infections with Campylobacter-like organisms are
      characterized by epithelial cell hyperplasia. 5) Hemorrhagic colitis in humans,
      caused by enterohemorrhagic E. coli strains, is characterized by mucosal
      hemorrhage and edema indicative of vascular necrosis. 6) Most of these lesions
      are accompanied by some degree of inflammation. Neurophils and lymphocytes
      mediate some of the structural and functional changes characteristic of these
      infections. Some changes are mediated directly by microbial products. Additional
      examples of the complexity of these diseases are: 1) Edema disease of swine is
      characterized both by adherent E. coli and vascular necrosis (each process
      mediated by a different bacterial virulence attribute). 2) Rotavirus infections
      are characterized both by destruction of villous epithelial cells and
      compensatory hyperplasia of crypt epithelial cells. 3) There is suggestive
      evidence that enterohemorrhagic E. coli infections may involve: a) destruction of
      epithelial brush border by attaching-effacing E. coli, b) neutrophil mediated
      epithelial cell destruction, c) Shiga-like toxin mediated epithelial cell
      destruction and d) Shiga-like toxin mediated vascular necrosis which in turn
      causes ischemic damage to epithelium.

PMID- 9191987
TI  - Application of intestinal xenografts to the study of enteropathogenic infectious
      disease.
AB  - We have developed, characterized and utilized paired segments of fetal intestine
      subcutaneously transplanted into heterogenic nude or SCID mice as a model system
      for the study of viral, bacterial and protozoal pathogens. The xenografted
      intestine matures in the recipient mouse and is biochemically and anatomically
      comparable to intestine from age-matched, whole-animal controls. The grafted
      tissue is free of ingesta, intestinal flora, extra-intestinal secretions and host
      immune functions. The transplanted intestine is long-lived and easily accessible
      to manipulation and harvest. Tissue from a single fetal donor can be used to
      create numerous xenografts allowing for tightly controlled experiments.
      Xenografts enable the study of species-specific intestinal pathogens in the
      homologous intestinal tissue thus preserving biological applicability of results.
      Xenografts can be used to study pathogenesis, pathophysiology and therapeutics of
      enteric disease in situations where such study might otherwise be prohibitively
      expensive or confounded by intercurrent variables inherent to whole animals.
      Xenografts have important advantages over in vitro models that may not
      approximate the in vivo biology of the intestine in the disease process.

PMID- 9191988
TI  - An overview of immunological and genetic methods for detecting swine
      coronaviruses, transmissible gastroenteritis virus, and porcine respiratory
      coronavirus in tissues.
AB  - Transmissible gastroenteritis (TGE) is an enteric disease of swine caused by a
      coronavirus, designated as transmissible gastroenteritis virus (TGEV). Commonly
      used methods for TGEV detection include viral isolation and detection of the
      viral antigen by indirect immunofluorescence (IFA), immunoperoxidase, and
      immunogold silver staining. Each of these techniques has some advantages and
      disadvantages. In general IFA and immunohistochemistry are preferred over viral
      isolation as TGEV isolation is not very reliable because not all field isolates
      replicate in cell cultures. The diagnosis of TGEV has become more complicated
      since the emergence of porcine respiratory coronavirus (PRCV). PRCV is believed
      to be a TGEV mutant, and can not be easily differentiated from TGEV by
      immunological tests. Nucleic acid probes and polymerase chain reaction (PCR) have
      successfully been used to detect and differentiate these viruses. These
      techniques can detect viral nucleic acids in the specimen but do not provide
      information on the cell types infected by these viruses. Recently we have
      developed isotopic and nonisotopic in situ hybridization techniques (ISH) for the
      detection of these viral nucleic acids in formalin-fixed paraffin-embedded
      tissues. Furthermore, this procedure can differentiate between TGEV- and PRCV
      infected cells. By ISH, TGEV is detected in the mature absorptive enterocytes of
      tissues infected by TGEV and the crypt epithelial cells are also infected but to
      a lesser extent. For PRCV, the main infected cells are epithelial cells of the
      bronchioles, type II pneumocytes, and alveolar and septal macrophages. ISH is an
      excellent tool for studying molecular pathogenesis of these two viruses
      especially when used in combination with immunohistochemistry.

PMID- 9191989
TI  - Pathogenesis of O157:H7 Escherichia coli infection in neonatal calves.
AB  - Cattle have been implicated as an important reservoir of Shiga-like toxin
      producing Escherichia coli (SLTEC) O157:H7, enterohemorrhagic E. coli (EHEC) that
      cause hemorrhagic colitis and hemorrhagic uremic syndrome in humans. Naturally-
      or experimentally-infected cattle can shed low levels of E. coli O157:H7 long
      term, but little is known about the pathogenesis of E. coli O157:H7 infection in
      cattle. E. coli O157:H7 induce characteristic attaching and effacing (A/E)
      mucosal lesions in ceca and colons of 1-day-old gnotobiotic piglets and this
      model is used to study the pathogenesis of SLTEC infections. A/E lesions were not
      detected in histologic sections of the intestines from adult cattle or 3- to 14
      week-old calves infected with E. coli O157:H7. Our objective was to determine if
      E. coli O157:H7 induce A/E lesions in neonatal calves. Colostrum-deprived calves
      (< 12-h-old) were bottle-fed with antibiotic-free milk replacer containing 10(10)
      colony forming units (CFU) of O157:H7 (SLT-I+, SLT-II+) or nonpathogenic E. coli,
      necropsied 18 h postinfection and their intestines examined histologically.
      Bacterial attachment, effacement of microvillous borders, and destruction of
      epithelium were observed in the intestines of the neonatal calves inoculated with
      E. coli O157:H7. No lesions were observed in calves inoculated with nonpathogenic
      E. coli. The distribution of intestinal lesions in neonatal calves resembled that
      in gnotobiotic pigs. Neonatal calves are apparently more susceptible to A/E
      lesions induced by E. coli O157:H7 than are older calves or adult cattle and
      provide a model for studying the pathogenesis of E. coli O157:H7 infections in
      cattle.

PMID- 9191990
TI  - Variation in virulence in the gnotobiotic pig model of O157:H7 Escherichia coli
      strains of bovine and human origin.
AB  - Escherichia coli strains of serotype O157:H7 have been incriminated in outbreaks
      and sporadic cases of food-borne illness, including diarrhea, hemorrhagic
      colitis, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Food
      producing animals, particularly cattle, are believed to be reservoirs of the
      organism. Whether all strains of bovine origin pose human health risk is unknown
      and was the impetus for this investigation. We compared the virulence of ten SLT
      I, SLT-II, and eae DNA probe-positive O157:H7 strains from cattle to 10 like
      strains associated with human diarrheal disease outbreaks for virulence in one
      day-old gnotobiotic pigs. All strains caused diarrhea, and only four pigs
      inoculated with either of two bovine strains failed to develop that condition.
      Signs of central nervous system disease, death, debilitation requiring euthanasia
      before the end of an eight day observation period, and/or encephalomalacia
      occurred in 32/42 pigs inoculated with the strains isolated from human beings,
      13/39 pigs inoculated with strains from cattle, and 7/7 pigs inoculated with a
      positive control strain. More strains of human origin (9/10) than bovine origin
      (5/10) caused these effects. The results of this study indicate considerable
      variability in virulence of O157:H7 strains possessing the same known virulence
      determinants, and suggest that disease outbreaks tend to be caused by the more
      virulent of these strains.

PMID- 9191991
TI  - Attaching and effacing E. coli. Microscopic and ultrastructural observation of
      intestinal infections in pigs.
AB  - Pigs aged from neonate to 8 weeks with naturally occurring diarrhoea were
      submitted to a Veterinary Investigation Centre for routine diagnosis. They were
      retrospectively found to be infected with "attaching and effacing" E. coli (AEEC)
      on histological and ultrastructural examination of the intestinal tract.
      Subcultures of E. coli isolated from some of the affected pigs were tested
      against standard anti-sera and probed for the presence of verotoxin (VT) and
      "cae" genes. One strain of E. coli was positive for the VT gene and three VT
      negative strains possessed the "cae" gene. This preliminary report suggests that
      in naturally occurring diarrhoea of suckling and weaned pigs, AEEC infection can
      be identified by histological examination of the intestinal mucosa and confirmed
      by electron microscopy, in the abscence of infection by recognised enteric
      pathogens on microbiological examination.

PMID- 9191992
TI  - Dynamics of Clostridium difficile infection. Control using diet.
AB  - Understanding the dynamics of the establishment of C. difficile within the gut is
      vital to effective prevention, control and therapy of disease due to this
      nosocomial pathogen. Factors affecting the establishment of C. difficile in the
      gut were investigated including the role of bacterial metabolic products (BMPs),
      the composition of colonic flora, diet, and properties of the infecting strain.
      Concentrations of 9/12 bacterial metabolic products (BMPs), both volatile and non
      volatile were significantly higher in mice which eliminated oral challenge with
      10(8) spores of C. difficile (E mice) than in mice harbouring the organism (H
      mice). Growth of C. difficile in vitro was inhibited 10(4) fold at combinations
      of BMPs at concentrations found in stools of E mice but not in stools of H mice.
      The in situ production and concentrations of BMPs were increased by augmenting
      the amount of fermentable fibre in the diet. This resulted in elimination of C.
      difficile from 6/7 C. difficile colonized mice within 6 days of beginning a diet
      containing 20% fermentable fibre. Whereas mice fed diets containing 2%
      fermentable fibre or 20% non-fermentable fibre continued excreting the organism.
      Elimination of C. difficile was associated with increased concentrations of BMPs
      and changes in the numbers of organisms already present within the colonic flora.
      Properties of two microbial phenotypes (smooth (S), and rough (R)) of one strain
      of C. difficile were examined in vitro and the ID50s determined. The S phenotype
      survived, germinated and grew in media containing higher concentrations of BMPs,
      acquired iron when grown under iron restriction, utilized haem and bound Congo
      red more readily than the R phenotype. In mice fed the 2% fermentable fibre diet
      the ID50 for the S phenotype was 10(3) spores and 10(8) spores for the R
      phenotype, whereas for mice fed the 20% fermentable fibre diet it was > 10(6)
      spores for the S phenotype. The ability of this opportunistic pathogen to adapt
      to changing environmental conditions is an important factor in determining
      whether the organism will colonize and cause disease. Diets supplemented with
      fermentable fibre may be a valuable method of preventing and treating C.
      difficile related disease.

PMID- 9191993
TI  - Detection and differentiation of 3 K88 serogroups using polymerase chain reaction
      techniques. K88 serogroup detection and differentiation.

PMID- 9191994
TI  - Specific identification of Escherichia coli O157:H7 using a multiplex PCR assay.

PMID- 9191995
TI  - Variation in manifestation of E. coli H7 antigen.

PMID- 9191996
TI  - Verotoxigenic Escherichia coli in slaughter cattle and ground beef in South
      Dakota.

PMID- 9191997
TI  - Immunoglobulin response to Salmonella enteritidis outer membrane proteins. Use
      for evaluating infectious status.

PMID- 9191998
TI  - Sequence analysis of VP7 gene of a bovine rotavirus with G6 subtype.

PMID- 9191999
TI  - Detection of the fimbrial gene F18 (F107) from swine enteritis Escherichia coli.

PMID- 9192000
TI  - A chick model for the study of "attaching and effacing Escherichia coli"
      infection.
AB  - Young chicks were experimentally infected with 6 strains of AEEC isolated from
      calves, pigs, chicks, and humans. AEEC colonized the cecum of chicks and induced
      the AE lesions on the mucosal surface. In the early stages of the AE lesions,
      AEEC attached to the enterocyte were enfolded with the microvilli. In the
      advanced stages, microvilli and cytoskeletons of the enterocytes were disrupted,
      and cytoplasmic cups and pedestal-like protrusions were formed on the cell
      surface. The AE lesions interconnected with the adjacent lesions, and it formed
      the network on the mucosal surface. Leukocytes infiltrated in the mucosa
      associated with AE lesions, and lymphatic nodules also developed. The results of
      these studies support the conclusion that chicks can be used as a model for the
      study of the lesions caused by AEEC.

PMID- 9192001
TI  - Immunological cross reactivity of eaeA (intimin) from E. coli that cause
      attaching and effacing lesions in humans and rabbits.

PMID- 9192002
TI  - Characterization of the EaeA protein of attaching and effacing Escherichia coli
      O45 from pigs using monoclonal antibodies.

PMID- 9192003
TI  - Interactions between the enteric pathogen and the host. An assortment of
      bacterial lectins and a set of glycoconjugate receptors.
AB  - Bacteria have been associated with a wide variety of syndromes in animals and
      humans. These include enteropathies, urinary infections, meningitis and
      septicemia. Among the distinct set of tactics to prevail within the host, is the
      ability of bacteria to adhere to cellular targets. Adhesion to the gut by enteric
      bacteria occurs via several types of adhesins. During the last 15 years, much
      information has become available on bacterial adhesins and mechanisms governing
      bacteria-host interactions. Due to their location on the cell surface,
      establishing a carbohydrate frontier, and their inherent variability,
      glycosphingolipids and glycoproteins provide a wide range of binding sites for
      bacteria, toxins and more generally lectins. Bacterial lectins are localized
      either on the tip or along fimbrial filaments or on nonfimbrial structures. We
      examine in this short review, a collection of pathogen lectins, through their
      different receptor specificities. For sialic acid-binding lectins, the
      conformation of terminal sialic acid is essential for adhesion, whereas for other
      bacterial lectins, complementary sugars may be arranged in specific linear and/or
      branched sequences. Finally, it appears that the composition and structure of
      cell carbohydrates could in part explain the bacterial tropism and susceptibility
      or resistance of the host to enteric diseases.

PMID- 9192005
TI  - Characterization of a porcine enterocyte receptor for group A rotavirus.
AB  - We have identified, purified to apparent homogeneity and chemically characterized
      a biologically-relevant porcine enterocyte receptor for group A porcine
      rotavirus. Ceramide glycanase digestion followed by acid hydrolysis and
      monosaccharide compositional analyses indicated the receptor is a family of two
      GM, gangliosides, one containing N-glycolyl-neuraminic acid and the other N
      acetylneuraminic acid. Both gangliosides displayed dose-dependent inhibition of
      rotavirus binding to, and infectivity of, host cells. Inhibition of infectivity
      in a focus-forming-unit-reduction assay was achieved with as little as 2 nmols of
      NeuGcGM3 (50% inhibition with 3.97 nmol) or NeuAcGM3 (50% inhibition with 9.84
      nmol) per 10(4) FFU of virus. Preliminary data suggest specific porcine GM3
      carbohydrate fine structure or spatial orientation of the sialyloligosaccharide
      epitopes of the holoGM3 gangliosides may be crucial to enterocyte receptor
      recognition by rotavirus. We have quantified both NeuGcGM3 and NeuAcGM3 in
      enterocytes of various-aged pigs from newborn through 16 weeks and have found
      with increasing age the amount of both GM3 derivatives, especially NeuGcGM3 per
      gram (dry weight) intestinal brush border decreases rapidly from newborn through
      4 weeks of age. These results may help explain the age-sensitivity of piglets to
      severe rotavirus diarrhea.

PMID- 9192004
TI  - Virus-receptor interactions in the enteric tract. Virus-receptor interactions.
AB  - Expression of specific virus receptors on the surface of intestinal epithelial
      cells or M cells can determine whether or not a animal is susceptible to
      infection with an enterotropic virus. Receptors for many animal viruses have been
      identified. The specificity of virus-receptor interactions clearly affects the
      species specificity of virus infection, and in some instances may be an important
      determinant of viral tissue tropism. In this paper, the specificity of
      coronavirus-receptor interactions is summarized. Porcine and human coronaviruses
      utilize aminopeptidase N as their receptors, but in a species-specific manner.
      Mouse hepatitis virus uses several rodent glycoproteins in the carcinoembryonic
      antigen family as receptors. In addition, some coronaviruses can interact with
      carbohydrate moieties on the cell surface. Understanding the molecular mechanisms
      of virus-receptor interactions may lead to development of novel strategies for
      the control of enteric viral diseases.

PMID- 9192006
TI  - A 50 kDa membrane protein from bovine kidney cells is a putative receptor for
      bovine viral diarrhea virus (BVDV).
AB  - A 50 kDa cell surface protein from MDBK cells has been identified as a putative
      receptor for bovine viral diarrhea virus (BVDV) by using a BVDV specific anti
      idiotypic antibody (Anti-D89). This study delineates further characterization of
      the receptor protein. Protease treatment of cultured MDBK cells adversely
      affected the receptor thus abolishing the binding of anti-D89 to the cells.
      However, pretreatment of the cells with either phospholipases or glycosidases did
      not signficantly alter the extent of anti-D89 binding. Additionally, pretreatment
      of cell monolayers with proteases decreased BVDV attachment and replication in
      the cells. These results suggested that the receptor for BVDV is a protein in
      nature, and glycosylation and phosphorylation of the receptor protein may not
      play a direct role in BVDV attachment to cells. The BVDV receptor protein
      gradually regenerated on cells when they were maintained in culture following
      protease treatment. The purified 50 kDa receptor protein also significantly
      inhibited BVDV infection in a plaque reduction assay.

PMID- 9192007
TI  - Fimbrial adhesins of Salmonella typhimurium. Role in bacterial interactions with
      epithelial cells.
AB  - S. typhimurium initiates infection of its mammalian host by attachment to mucosal
      surfaces in the intestine and subsequent invasion of epithelial cells. To date,
      three S. typhimurium fimbrial operons, fim, lpf and pef, have been characterized.
      This analysis suggests that fimbrial adhesins fulfill multiple functions during
      the initial phase of an infection. In addition to their role in colonization of
      the small intestine, adhesins contribute to the tissue tropism for Peyer's
      patches, which is characteristic for Salmonella infections. Furthermore, by
      mediating the initial contact to epithelial cells, fimbrial adhesins appear to be
      necessary for invasion and possibly for elicitation of an inflammatory response.
      Thus, fimbriae are important virulence factors of S. typhimurium and their future
      analysis promises to yield fascinating new insights into host-parasite
      interactions of this pathogen.

PMID- 9192008
TI  - Phenotypic and genotypic profiles of human, canine, and porcine spirochetes
      associated with colonic spirochetosis correlates with in vivo brush border
      attachment.
AB  - A group of phenotypically and genotypically distinct weakly beta-hemolytic
      intestinal spirochetes (WBHIS) have been associated with a diarrheal disease of
      humans, dogs and swine, designated colonic spirochetosis (CS). Because attachment
      of spirochetes to the brush border of colonic enterocytes is a consistent feature
      of CS, it may represent an important virulence mechanism. In this study, pure
      cultures of WBHIS obtained from humans, dogs, and swine with clinical signs or
      lesions of CS were compared with Serpulina innocens using biochemical, genotypic
      and an in vivo brush border attachment assay CS-associated WBHIS did not form
      genotypic and an in vivo brush border attachment assay CS-associated WBHIS did
      not form indole, but hydrolyzed hippurate. Analysis of genomic DNA using
      arbitrarily primed-PCR (AP-PCR) revealed that the CS-associated WBHIS had a
      closely related pattern which was distinctly different from that of S. innocens.
      For in vivo brush border attachment assays, one-day old chicks were inoculated by
      crop gavage with either sterile trypticase soy broth or broth containing either
      S. innocens or CS-associated WBHIS. On day 7 post-inoculation, the ceca of sham
      inoculated control chicks and S. innocens-inoculated chicks had tall columnar
      enterocytes without spirochetes, and no spirochetes were isolated by culture on
      selective medium. Focal to segmental attachment of spirochetes to the brush
      border of superficial enterocytes was present in the ceca of chicks inoculated
      with WBHIS, and weakly beta-hemolytic spirochetes with effacement of the
      microvillous brush border of colonic enterocytes. Complete agreement between
      hippurate hydrolysis, specific- and AP-PCR assays and in vivo brush border
      attachment studies confirms the enteropathogencity of CS-associated WBHIS.

PMID- 9192009
TI  - A three-receptor model for the interaction of the K88 fimbrial adhesin variants
      of Escherichia coli with porcine intestinal epithelial cells.
AB  - Four phenotypes of pigs distinguished by the variant(s) of K88 fimbrial adhesin
      (K88ab, K88ac, K88ad) that bind to their intestinal epithelial cells (I-none of
      the variants, II-K88ad, III-K88ab and K88ac, and IV-all three variants) have been
      identified. We hypothesize that the differences between the phenotypes are
      defined by the presence or absence of K88 adhesin receptors. We propose a three
      receptor model to account for the observed phenotypes: 1) Receptor bed which
      binds all three variants and is found in phenotype IV, 2) Receptor be which binds
      K88ab and K88ac and is found in phenotype III and IV, and 3) Receptor d which
      binds K88ad and is found in phenotype II. We have identified the be receptor
      activity as a pair of mucin-type sialoglycoproteins (210 and 240 kDa). Although
      neither the bcd nor d receptor has been identified biochemically, their presence
      has been established using both blocking and receptor localization studies.
      Blocking studies using phenotype IV brush borders demonstrated that K88ab and
      K88ac fimbriae block the binding of E. coli expressing any of the K88 variants,
      but K88ad fimbriae block only K88ad E. coli binding. These results indicate that
      two receptors (bcd and bc) exist in the phenotype IV animals. Receptor
      localization studies on intestinal sections from phenotype IV animals showed that
      K88ab and K88ac adhesin binding is continuous from the crypt to the tip of the
      villus. The binding of the K88ad adhesin binding is multifocal in phenotype IV
      pigs, but continuous from crypt to tip of the villus in sections of phenotype II
      pigs. These studies verify the presence of two receptors (bcd and bc) in
      phenotype IV animals, and indicate that the K88ad receptor in phenotype IV
      animals (bcd) is different than in phenotype II animals (d).

PMID- 9192010
TI  - Fimbrial colonisation factors F18ab and F18ac of Escherichia coli isolated from
      pigs with postweaning diarrhea and edema disease.
AB  - During the last 5 years at least four new types of colonisation factors have been
      described in association with porcine postweaning diarrhea and edema disease
      strains of E. coli. Recently, evidence was presented that these fimbrial factors
      are closely related to each other, and therefore the common denomination F18 was
      proposed. Until now, two variants F18ab and F18ac were identified that can be
      distinguished by serology. Alternatively, to circumvent elaborate growth
      conditions for the optimal expression of F18 fimbriae in vitro, PCR and
      subsequent restriction enzyme digestion of the amplification product can be used
      to differentiate F18ab from F18ac positive isolates. Reports that studied the
      prevalence of F18 positive E. coli show that this factor is present in about 30%
      to more than 50% of the PWD or ED strains negative for F4, F5, F6 or F41.
      Susceptibility of pigs to colonisation depends on the availability of intestinal
      receptors, and is under the control of a chromosomal locus. In young pigs
      susceptibility increases with age. Intestinal infection with F18 positive E. coli
      induces protection against repeated colonisation with E. coli bearing the
      homologous or the heterologous fimbrial variant of F18. Finally, preliminary
      passive protection studies suggest that F18 antibodies inhibit the colonisation
      of the pig's intestine by F18ab and F18ac positive strains.

PMID- 9192011
TI  - Plasminogen receptors. Turning Salmonella and Escherichia coli into proteolytic
      organisms.
AB  - We evaluated in vitro the hypothesis that bacterial adhesiveness to the mammalian
      extracellular matrix and the activation of plasminogen on bacterial plasminogen
      receptors promote bacterial penetration through basement membranes. We used the
      strain SH401 of Salmonella enterica serovar Typhimurium, which adheres to the
      high-mannose chains of laminin, a major glycoprotein of basement membranes, and
      expresses plasminogen receptors. Bacterium-bound plasmin was able to degrade
      laminin and extracellular matrix preparations as well as to potentiate the
      penetration of bacteria through a reconstituted basement membrane. The results
      suggest that metastatic tumour cells and bacterial pathogens use similar
      mechanisms to penetrate through tissue barriers.

PMID- 9192012
TI  - Evaluation of DNA "fingerprinting" for predicting the potential of E. coli
      O157:H7 isolates to cause hemolytic uremic syndrome (HUS).
AB  - Escherichia coli O157:H7 has been recognized since 1982 as a serious human
      pathogen spread by contaminated food and water. Pulsed-field gel electrophoresis
      has proven useful for identification of specific isolates/strains of this
      organism. Hemolytic uremic syndrome (HUS), generally occurring in children or the
      aged, is the most severe sequela associated with E. coli O157:H7 infection. The
      presently described work was designed to compare the genomic profile of isolates
      known to have caused HUS with those having had no such involvement. We asked the
      question: "Can we develop the means to recognize an 'HUS-prone' E. coli isolate
      and thereby alert medical personnel to the increased risk?" Twenty-two HUS
      related and 10 HUS-unrelated E. coli O157:H7 samples were chosen for genomic
      analysis. Isolates were cultured overnight prior to being embedded in agarose gel
      plugs. Plugs were digested, using Xbal restriction endonuclease, and subjected to
      pulsed-field gel electrophoresis (PFGE) for 20 hours. Gels were stained with
      ethidium bromide, photographed under ultraviolet light, and Southern blotted.
      Radiolabeled toxin gene probes were used for hybridization assays. The two
      classes of isolates were compared by optical imaging software. A computer
      generated dendrogram, based on restriction profiles, offered strong initial
      evidence that the HUS sequela may be produced by a particularly virulent and
      identifiable clone. The predictive value of this finding appears to be
      substantial.

PMID- 9192013
TI  - Fermentation and growth response of a primary poultry isolate of Salmonella
      typhimurium grown under strict anaerobic conditions in continuous culture and
      amino acid-limited batch culture.
AB  - Salmonella typhimurium is a significant hazard to consumer health that is carried
      asymptomatically in poultry gastrointestinal tracts. Nurmi cultures may prevent
      Salmonella colonization in young chicks, but the mechanism of competitive
      exclusion is unclear. Modeling Salmonella's metabolism in pure culture may allow
      for greater definition in choosing strains for Nurmi cultures. The growth rates
      and affinity constants of S. typhimurium growing in amino acid-limited conditions
      were determined in batch culture and compared to primary poultry isolates of
      cecal strains. Serine and NH4Cl were the best N sources for growth of all
      organisms tested in this study. The fermentation response of S. typhimurium was
      also monitored in continuous culture at a slow dilution rate of 0.021 h-1. S.
      typhimurium was found to adapt to VL media, with trends in protein disappearance,
      Yglucose, and Yprotein. This may show that amino acid or protein concentrations
      may be an integral component of the initial establishment of S. typhimurium in
      the cecum.

PMID- 9192014
TI  - Distribution of K88-adhesive and non-adhesive phenotypes among four popular
      breeds of pigs.

PMID- 9192015
TI  - Elucidating the cell entry mechanisms of porcine rotaviruses.

PMID- 9192016
TI  - Adherence and invasion of Aeromonas caviae to monolayer cells. Adherence and
      invasion of Aeromonas caviae.

PMID- 9192017
TI  - F107-binding immunoassay detects porcine intestinal receptors for F107 fimbriae
      of Escherichia coli.

PMID- 9192018
TI  - Intracellular transport and processing of protein toxins produced by enteric
      bacteria.
AB  - Bacterial toxins are associated with disease in humans and animals. Toxins can
      either be preformed in food or produced by bacteria in the intestine. There are
      two types of toxins: heat-labile protein toxins and heat stabile toxins. Heat
      labile toxins are produced by Bacillus cereus, Clostridium perfringens,
      Escherichia coli, and Vibrio cholerae, and heat-stabile enterotoxins consisting
      of relatively few amino acids are produced by Escherichia coli and acts by
      activation of guanylate cyclase. Similarly, heat-stabile entero-toxins are also
      produced by Staphylococcus aureus, a common cause of food poisoning in the United
      States, and Yersenia enterocolitica. Protein toxins produced by enteric bacteria
      can intoxicate intestinal cells and can also be taken up from the gut and reach
      other cells in the body. For example the Shiga-like toxins (vero-toxins) can
      intoxicate endothelial cells in the kidney and cause kidney failure.
      Intracellular transport and processing of a few of the protein toxins produced by
      enteric bacteria, namely Clostridium difficile toxin A and B, cholera toxin and
      the related heat-labile toxin produced by Escherichia coli, and Shiga toxin and
      Shiga-like toxins are presented.

PMID- 9192019
TI  - Murine model of rotavirus infection.
AB  - The murine model of homologous rotavirus infection has been used to study the
      determinants of protection. The local IgA immune response appears to be the
      critical factor in generating protective immunity after natural infection. A
      series of knockout mice were used to evaluate the contribution of T cells and B
      cells to immunity and resolution from primary infection. Both arms of immune
      system played a role in the resolution of primary infection but antibody was much
      more important for prevention of reinfection.

PMID- 9192020
TI  - Cloning of the RDEC-1 locus of enterocyte effacement (LEE) and functional
      analysis of the phenotype on HEp-2 cells.
AB  - EPEC Escherichia coli are an important cause of epidemic diarrhea in infants. The
      disease is characterized by attaching and effacing (A/E) lesions where the
      bacteria attach intimately to the enterocyte surface resulting in localized
      destruction of microvilli. A 35-kb chromosomal locus termed LEE (locus of
      enterocyte effacement) in an EPEC strain (E2348/69) has recently been found and
      is thought to contain all the necessary genes for A/E lesions. RDEC-1 is a strain
      of E. coli that causes diarrhea in rabbits by a similar mechanism and serves as a
      model for human EPEC disease. We report 1) the cloning of the RDEC-1 LEE, 2) show
      that the RDEC-1 LEE is similar in size to the LEE in E2348/69, 3) the RDEC-1 LEE
      possesses all four regions of the E2348/69 LEE, 4) there are restriction site
      polymorphisms between the RDEC-1 LEE and that of E2348/69, and 5) the RDEC-1 LEE
      clone is functionally similar to E2348/69 in its fluorescent actin staining test
      and suggests that the LEE may be sufficient for the production of A/E lesions by
      these strains.

PMID- 9192021
TI  - Characterization of the agfBA fimbrial operon encoding thin aggregative fimbriae
      of Salmonella enteritidis.

PMID- 9192022
TI  - Cell membrane permeability- and mitochondrial dysfunction-inducing activities in
      cell free supernatants from Serpulina hyodysenteriae serotypes 1 and 2.

PMID- 9192023
TI  - CO2 regulation of virulence genes in enteropathogenic Escherichia coli.

PMID- 9192024
TI  - Binding of human enterotoxigenic Escherichia coli expressing coli surface antigen
      6 to rabbit intestinal enterocytes and glycoproteins.

PMID- 9192025
TI  - Functional analysis of Serpulina hyodysenteriae hemolysin lytic activity.

PMID- 9192026
TI  - Cloning, sequencing, and expression of a Campylobacter jejuni periplasmic binding
      protein (P29) involved in histidine transport.

PMID- 9192028
TI  - AF/R2 adhesin and cytopathic effect as virulence traits of diarrhea-inducing
      Escherichia coli O103 in European rabbit.

PMID- 9192027
TI  - Norepinephrine-induced growth and alteration of molecular fingerprints in
      Escherichia coli O157:H7.

PMID- 9192029
TI  - Apoptosis of crypt cells and inflammatory reactions in the small intestine of
      mice challenged with staphylococcal enterotoxin B.

PMID- 9192030
TI  - Serovar specific differences in Salmonella survival within macrophage cells.

PMID- 9192031
TI  - Genetics of virulence of enteropathogenic E. coli.
AB  - Enteropathogenic E. coli (EPEC) are a major cause of diarrhea in infants
      throughout the world. Although this pathogen was described 50 years ago, it is
      only recently that the pathogenic mechanisms employed by this organism have been
      elucidated. The characteristic histopathology induced by this organism, called
      "attaching and effacing", consists of intimate adherence of the bacterium to the
      epithelial cell with marked cytoskeletal changes including effacement of
      microvilli. A 35 kb region of chromosomal DNA, called the LEE for locus of
      enterocyte effacement has recently been described which contains all known genes
      necessary for production of this characteristic histopathology. Within this
      region is the eae gene encoding intimin, a 94 kDa OMP involved in intimate
      adherence. Also within this region are genes encoding proteins secreted
      extracellularly by EPEC (esp) and a type III secretion apparatus (sep) which
      shares homology with similar systems in Yersinia, Shigella, and Salmonella.
      Additional genes on a 60 MDa plasmid encode a type IV pilus (BFP) and a positive
      transcriptional activator (per) of multiple chromosomal and plasmid virulence
      genes.

PMID- 9192032
TI  - Interactions of enteric pathogens with human epithelial cells. Bacterial
      exploitation of host processes.
AB  - Many bacterial pathogens interact with surfaces on the body resulting in disease.
      These interactions are usually tightly regulated. Several of these pathogens also
      exploit host processed which contribute to their pathogenesis. Enteropathogenic
      existing epithelial cells using sophisticated mechanisms that exploit existing
      epithelial signal transduction pathways and host cytoskeleton components. Unlike
      EPEC, Salmonella species actually enter into epithelial cells (invade) and
      function as intracellular parasites. During invasion Salmonella exploit various
      host signal transduction pathways and cause cytoskeletal rearrangements.
      Salmonella enter an intracellular vacuole which remains separated from the main
      epithelial cell, Salmonella species trigger the formation of a novel
      intracellular organelle which is associated with intracellular growth. Comparison
      of the virulence mechanisms used by these two pathogens and their exploitation of
      epithelial cells illustrates several principles used by bacterial pathogens to
      cause disease.

PMID- 9192033
TI  - Hemolysin phenotypes and genotypes of eaeA-positive and eaeA-negative bovine
      verotoxigenic Escherichia coli.
AB  - Intimin or EaeA protein has been implicated in the attaching/effacing lesion
      caused by entero-hemorrhagic Escherichia coli (EHEC) in the intestine but it is
      not produced by all EHEC and is therefore not adequate as a marker for EHEC.
      Hemolysins are produced by a high percentage of verotoxigenic E. coli (VTEC) and
      could be a marker for EHEC, but their distribution and relation to virulence are
      not known. We used PCR amplification to determine the presence or absence of eaeA
      sequences in 281 VTEC isolates from the feces of healthy cattle. There were 101
      eaeA-positive isolates, which belonged to O groups 5, 26, 69, 80, 84, 98, 103,
      111, 119, 145, 157 and 108 eaeA-negative isolates, which belonged to O groups 8,
      22, 38, 113, 119, 116, 132, 153, 156 or untypable. All isolates were tested for
      hemolysis on horse blood agar and on washed sheep blood agar. PCR amplification
      was used to test for EHEC hemolysin, Ehly1, Ehly2 and alpha-hemolysin D
      sequences. Among eaeA-positive isolates 98% were positive for EHEC hemolysin
      sequences and were hemolytic on washed sheep red blood cell agar; the
      corresponding percentage for eaeA-negative isolates was 36%. Ehly1 and Ehly2
      sequences were present in only 11 isolates (O groups 26, 84, 119 and 132). None
      of the eaeA-positive and 13 of the eaeA-negative isolates (including all 11
      isolates of O group 132) were positive for alpha-hemolysin D gene sequences by
      PCR and alpha-hemolysin production on horse blood agar. We conclude that since
      Ehly1, Ehly2 and alpha-hemolysin occur at low frequency among bovine VTEC and
      serotypes implicated in human disease they are unlikely to be significant
      virulence factors. In contrast, EHEC hemolysin was present in almost all eaeA
      positive VTEC isolates and in approximately one-third the eaeA-negative ones; it
      may be both a virulence marker and virulence factor but further testing is
      required. The study identified isolates with all combinations of eaeA and EHEC
      hly, which may be useful for further testing.

PMID- 9192034
TI  - Regulators of Escherichia coli K99 region 1 genes.
AB  - Expression of K99 is highly regulated being dependent on 8 K99-specific genes and
      several host-specific genes including cyclic AMP receptor protein (Crp) and
      leucine responsive protein (Lrp). The 8 K99-specific genes are organized into 3
      separately regulated clusters (regions I-III) with region I and II genes being
      dependent on Crp. Using TnphoA tagged K99 genes, Lrp was shown to be required for
      expression of region I genes. Differential methylation of GATC boxes is a common
      method by which Lrp functions as a regulator. Two GATC boxes are present adjacent
      to the 5' end of fanA, the first gene. Using the restriction enzymes Dpn I and
      Mbo I which recognize methylated and non-methylated GATC boxes, respectively, it
      was shown that differential methylation was not a mechanism regulating K99
      expression. Using a gel mobility shift assay and protein extracts from various
      strains, it was shown that a 625 bp DNA fragment adjacent to the 5' end of fanA
      bound protein prepared from Lrp+ strains but not from Lrp- strains. While region
      I genes also require CRP for expression, the same degree of gel shift was
      observed when the extract was prepared from a Crp- strain. The products of fanA
      and fanB are believed to be positive regulators. However, protein extracts from
      strains with or without fanA and fanB caused the same degree of gel shift. Thus,
      while there are a variety of regulators necessary for region I gene expression,
      only Lrp or Lrp regulated proteins bind to the promoter region 5' to fanA.

PMID- 9192035
TI  - Pathotypes of bovine verotoxigenic Escherichia coli isolates producing
      attaching/effacing (AE) lesions in the ligated intestinal loop assay in rabbits.
AB  - Effacement of the microvilli and intimate attachment to the enterocytes (AE
      lesions) are two common properties of enteropathogenic (EPEC) and many
      verotoxigenic (VTEC) E. coli isolates from humans and animals. However not all of
      the several chromosomal and plasmidic genes and loci involved in the pathogenesis
      of the human EPEC strain E2348/69 are present in EPEC and VTEC isolates from
      animal species. We here report that in addition to verotoxin-encoding genes,
      bovine VTEC isolates harbour a variant of the original eaeA gene, confirming
      previous results, but neither the eaf nor the hfp loci which are involved in
      early attachment stage, and that not all of them possess an eaeB gene, as
      determined by the colony hybridization assay. Have these bovine VTEC isolates
      lost some of the loci or are they not necessary for the production of AE lesions
      in vivo? We also report the results of the ligated intestinal loop assay in
      rabbits with several bovine VTEC isolates. The production of AE lesions was
      correlated with the presence of an eaeA gene, but not with the presence of an
      eaeB gene, and was of course independent of the presence of the eaf and bfp loci.
      The eaeA-negative VTEC isolates produced no AE lesions. Either the eaeB gene is
      unnecessary for the production of AE lesions in the rabbit ligated intestinal
      loop assay or bovine VTEC possess other loci coding for similar functions. As to
      the adhesins involved in the early attachment step of bovine VTEC, they are most
      probably specific to cattle.

PMID- 9192036
TI  - Pathogenicity and sequence analysis studies suggest potential role of gene 3 in
      virulence of swine enteric and respiratory coronaviruses.
AB  - Coronaviruses have been commonly associated with enteric and respiratory
      diseases. Two of the swine coronaviruses, namely transmissible gastroenteritis
      virus (TGEV) and porcine respiratory coronavirus (PRCV), have been extensively
      studied. TGEV replicates in both the enteric and respiratory tracts and causes
      enteric disease, whereas, PRCV replicates in the respiratory tract with limited
      to no replication in the enteric tract. We have isolated PRCV from swine herds
      with respiratory disease and have reproduced moderate pneumonia in gnotobiotic
      and conventionally reared pigs with two of the PRCV isolates. We have also
      identified two PRCV isolates with low virulence. One consistent difference that
      we have observed between PRCV isolates of different pathogenicities is in gene 3.
      The gene 3 is intact in the two virulent PRCV isolates, whereas gene 3 is altered
      in the two low virulence isolates. A similar observation has been reported for
      TGEV as a nonpathogenic TGEV mutant with a small plaque morphology had a deletion
      in gene 3. We have also observed that one of the low virulence PRCV isolates, IA
      1894, which has a deletion in gene 3, replicates poorly in cell cultures.
      Collectively these studies suggest that gene 3 may be an important determinant
      for in vivo virulence and in vitro replication of coronaviruses.

PMID- 9192037
TI  - Studies of the astrovirus signal that induces (-1) ribosomal frameshifting.
AB  - Human astroviruses use a (-1) ribosomal frameshift mechanism to regulate
      expression of the viral RNA-dependent RNA polymerase gene. To evaluate the
      efficiency of the astrovirus frameshift signal in cell culture, different regions
      of the frameshift signal were cloned into the rhesus rotavirus VP4 gene and
      expressed in an infection-transfection transient expression cell-culture system.
      The various astrovirus-VP4 constructs were transfected into BHK-21 cells infected
      with a recombinant vaccinia virus that expresses T7 RNA polymerase (vTF7-3). All
      constructs contain a T7 promoter, a picornavirus internal ribosome entry site,
      and a T7 terminator. Frameshifted and non-frameshifted proteins were
      distinguished by immunoprecipitation with monoclonal antibodies specific for
      either the VP4 amino- or carboxy-terminus. Frameshifting efficiency was
      calculated as the ratio of radioactive counts in the frameshifted protein to the
      total counts in both the frameshifted and nonframeshifted proteins as determined
      by Phosphorimager analysis. We found the efficiency of astrovirus frameshifting
      in intact cells to be 25-28%, significantly greater than the 5-7% efficiency
      reported previously in a cell-free uncoupled translation system. Since the
      transfected plasmid is expressed in the cytoplasm in the infection-transfection
      system, the frameshifting efficiency determined by this assay may be a more
      accurate reflection of the level of frameshifting for this RNA virus in which
      transcription and translation are likely coupled in the cytoplasm of infected
      cells. This hypothesis is supported by the observation that the level of
      astrovirus frameshifting is increased three-fold when evaluated in a cell-free
      coupled transcription-translation system. These studies also confirm in intact
      cells what was previously determined in cell-free studies: the shifty heptamer is
      an absolute requirement for astrovirus ribosomal frameshifting, but deletion of
      sequences downstream of the stem-loop that are potentially involved in pseudoknot
      formation does not affect the efficiency of frameshifting.

PMID- 9192038
TI  - Norepinephrine induced growth and expression of virulence associated factors in
      enterotoxigenic and enterohemorrhagic strains of Escherichia coli.
AB  - The small intestine is richly innervated by the sympathetic nervous system. High
      concentrations of monoamines, most notably norepinephrine, are found throughout
      the various intestinal layers. In order to determine whether norepinephrine is
      capable of influencing bacterial pathogenesis, the growth and production of
      virulence factors in ETEC and EHEC were examined in a physiologically relevant
      medium utilizing very low initial bacterial inoculums to more closely mimie in
      vivo conditions. The growth of ETEC strain B44 and the production of the K99
      pilus adhesin on a protein equivalent basis was greatly increased in the presence
      of norepinephrine. Growth of EHEC O157:H7 was also increased in norepinephrine
      containing medium as well as production of SLT-I and SLT-II. The ability of
      norepinephrine to increase both bacterial growth and expression of virulence
      factors was shown to be non-nutritional in nature. Given the abundant adrenergic
      innervation in the small intestine, these in vitro results suggest that the
      neurohumoral environment of the host may play a role in bacterial growth and
      expression of virulence factors.

PMID- 9192039
TI  - Unique Salmonella choleraesuis surface protein affecting invasiveness. Possible
      inv related sequence.
AB  - TnphoA mutagenesis of a Salmonella choleraesuis isolate recovered from septicemic
      infection of feeder pigs resulted in 56 PhoA+ KnR StrR mutants. Thirty-five
      mutants exhibited reduced levels of invasion in the Hep-2 cell model and were
      examined by SDS-PAGE Western Blot analysis using an anti-alkaline phosphatase
      antibody to visualize the insertion gene products. A mutant which produced a gene
      fusion product of 95 kDa and exhibited > 90% reduction in invasion was subcloned.
      A 10 Kb BamHI fragment of the chromosome containing the phoA insert was detected
      by hybridization and cloned into a pGEM vector. The resulting 1657 base sequence
      contained a 1104 bp ORF with two short regions of homology with S. typhimurium
      invF and invG. one region of homology with lcrD of Yersinia pseudotuberculosis
      but contained largely unique sequences not contained in Gene Bank. The full
      length sequence was not obtained as there was no stop codon detected. The % G+C
      was 44%, considerably lower than that of the Salmonella chromosome, but
      compatible with the proposed Yersinia origin of the inv genes. The NH2 387 a.a.
      sequence includes 5 transmembrane regions, resembling the model derived from the
      hydrophobicity plot of S. typhimurium InvA.

PMID- 9192040
TI  - A novel regulatory mechanism for a novel phase-variable outer membrane protein of
      Escherichia coli.
AB  - Antigen 43 (Ag43) is a prominent hetero-oligomeric protein complex in the outer
      membrane of Escherichia coli. It is composed of two subunits. alpha 43 (M(r) 60,
      000) and beta 43 (M(r) 53, 000) in 1:1 stoichiometry. alpha 43 is surface
      expressed, extends beyond the O-side chains of smooth lipopolysaccharide and is
      bound to the cell surface through an interaction with beta 43, itself an integral
      outer membrane protein, alpha 43 shows limited sequence homology with some
      enterobacterial adhesins. Expression of Ag43 is subject to reversible phase
      variation, the rates of variation from the Ag43+ve to Ag43-ve states in liquid
      minimal medium being approximately 2.2 x 10(-3), the corresponding rates from
      Ag43-ve to Ag43+ve states being approximately 1 x 10(-3). Phase switching of
      genes encoding Ag43 are transcriptionally regulated by DNA methylation
      (deoxyadenosine methylase [dam] mutants being "locked OFF") and by OxyR (oxyR
      mutants being "locked ON"). It is proposed that OxyR acts as a repressor of Ag43
      transcription by binding to unmethylated GATC sites in the regulatory region of
      the gene. Sequencing and mapping has identified Ag43 as the likely product of the
      metastable flu gene first described in 1980 by Diderichsen and responsible for
      colony form variation in E. coli.

PMID- 9192041
TI  - Adhesion of K88ab fimbriated E. coli in piglet small intestines in relation with
      iron transport molecules.
AB  - Enteropathogenic K88 fimbricated E. coli colonize the piglet small intestine. In
      swine, it has been previously established that some pigs lack intestinal
      receptors for K88 lectins and that these animals are resistant to infections by
      K88-positive E. coli. The receptor is inherited as a simple mendelian character.
      The interactions established between the glycoconjugate receptors of pig brush
      borders and K88 lectins are mediated by O- and N-linked glycoproteins which
      differ between adhesive and non-adhesive piglets. In this study the adhesion of
      E. coli K88+ in crossbred F2 (LW x MS) x (LW x MS) populations. By using in vitro
      brush border test, we observed modulation of the adhesion of K88 fimbriae and
      distinguished high and low affinity receptors. Furthermore, we correlated the
      attachment with glycoprotein pattern of epithelial cells and mucus. Epithelial
      cells and mucus contained several glycopeptides (from 42 to 74 kDa) recognized by
      K88ab fimbriae. The 74 kDa glycoprotein was characteristic of adhesive phenotype
      and was a mucosal transferrin (iTf). It appeared that iTf was more abundant in
      adhesive intestines than in non-adhesive ones, suggesting that
      susceptibility/resistance phenotype could be related to iron metabolism in the
      intestinal tract. Furthermore, we visualized the intestinal transferrin receptors
      on the brush border membrane of epithelial cells, probably implicated in iron
      absorption.

PMID- 9192042
TI  - Interaction of Escherichia coli producing cytotoxic necrotizing factor with HeLa
      epithelial cells.
AB  - Cytotoxic necrotizing factors (CNF) constitute a group a cell-associated proteic
      toxins of 110-115 kDa produced by some clinical isolates of Escherichia coli from
      man and animals. Purified CNFs are known to exacerbate actin polymerization in
      exposed cells, a property that has been ascribed to their ability to modify rho a
      small GTP-protein involved in the regulation of the cytoskeleton. We speculated
      that, in spite of their lack of excretion in broth culture supernatants, CNF
      might be expressed upon direct interaction of organisms with infected cells. To
      test this hypothesis, we set up a model of interaction using epithelial cell line
      HeLa and the CNF1-producing strain BM2-1, which is adherent to Hela cells. An
      interaction of four hour duration triggers the progressive development of a dose
      dependent cytopathic effect (CPE) with following characteristics: (1) intense
      cell enlargement with formation of a dense network of stress fibers, (2)
      inhibition of cell mitosis due to an irreversible block in G2/M transition phase,
      (3) nucleus swelling and fragmentation, and (4) cell death starting five days
      after infection. The three last features clearly differentiate CPE from the
      effect produced by CNF1 alone. In addition CPE, was not produced by cell-free
      culture supernatants nor abolished by an antiserum neutralizing CNF1. Tn5::PhoA
      insertion in the 3' end of cnf1 structural gene abolished CPE, which was not
      restored by trans complementation with cloned cnf1. These results demonstrate
      that CNF1-producing E. coli exert a specific pathogenic effect in HeLa cells,
      which is determined by cnf1 and at least one additional gene, located downstream
      cnf1.

PMID- 9192043
TI  - Adherence patterns of bacterial diarrheal agents in AIDS.

PMID- 9192044
TI  - In defense of mucosal surfaces. Regulation and manipulation of the mucosal immune
      system.
AB  - The mucosal immune system defends the host against pathogens, most of which
      invade through mucosal surfaces. Antigen sampling in the mucosal immune system in
      the intestine occurs constantly in specialized inductive sites known as gut
      associated lymphoreticular tissue or GALT. Antigen-primed cells then migrate to
      effector sites in the gut lamina propria and epithelium as well as to other
      mucosal tissues. A variety of strategies are being pursued to develop effective
      oral vaccines that will protect mucosal surfaces. Some approaches involve
      recently identified mucosal adjuvants, the best known of which is cholera toxin.
      One approach is illustrated in which antigen and adjuvant are incorporated in the
      inner water phase of a water-in-oil-in-water or multiple emulsion, thus
      protecting antigen and delivering it into GALT.

PMID- 9192045
TI  - Virus-like particle vaccines for mucosal immunization.
AB  - Viruses which infect the gastrointestinal tract are well suited for examining the
      immune response(s) to oral delivery of antigen and exploring the advantages and
      pitfalls of oral vaccines. We have used recombinant DNA techniques to produce
      nonreplicating self-assembled virus-like particles (VLPs) from two
      gastrointestinal viruses, rotavirus and Norwalk virus. Both of these viruses
      normally cause acute gastroenteritis in man or animals. The VLPs are
      morphologically and antigenically similar to the native virus and quite stable,
      features which are advantageous for their use as subunit vaccines. In addition,
      these VLPs could be useful as carriers of foreign epitopes from heterologous
      pathogens or of drugs which need to be delivered to the gastrointestinal track.
      This paper briefly reviews the properties of these VLPs made in insect cells and
      data showing their potential as subunit vaccines for parenteral or oral delivery.

PMID- 9192046
TI  - Comparative studies of the pathogenesis, antibody immune responses, and
      homologous protection to porcine and human rotaviruses in gnotobiotic piglets.
AB  - Gnotobiotic piglets serve as a useful animal model for studies of rotavirus
      pathogenesis and immunity. An advantage over laboratory animal models is the
      prolonged susceptibility of piglets to rotavirus-induced disease, permitting an
      analysis of cross-protection and active immunity. Studies from our laboratory of
      the pathogenesis of human rotavirus infections in gnotobiotic piglets have
      confirmed that villous atrophy is induced in piglets given virulent but not
      attenuated human rotavirus (Wa strain) and have revealed that factors other than
      villous atrophy may contribute to the early diarrhea induced. To facilitate and
      improve rotavirus vaccination strategies, it is important to identify correlates
      of protective immunity. Comparison of antibody immune responses induced by
      infection with virulent porcine and human rotaviruses (mimic host response to
      natural infection) with those induced by live attenuated human rotavirus (mimic
      attenuated oral vaccines) in the context of homotypic protection has permitted an
      analysis of correlates of protective immunity. Our results indicate that the
      magnitude of the immune response is greatest in lymphoid tissues adjacent to the
      site of viral replication (small intestine). Secondly there was a direct
      association between the degree of protection induced and the level of the
      intestinal immune response, with primary exposure to virulent rotaviruses
      inducing significantly higher numbers of IgA ASC and complete protection against
      challenge. These studies thus have established basic parameters related to immune
      protection in the piglet model of rotavirus-induced disease, verifying the
      usefulness of this model to apply new strategies for the design and improvement
      of rotavirus vaccines.

PMID- 9192047
TI  - Maternal immunization of pregnant cattle with recombinant VP8* protein of bovine
      rotavirus elicits neutralizing antibodies to multiple serotypes. Colostral
      neutralizing antibody by rotavirus VP8*.
AB  - Neonatal calf diarrhoea caused by bovine rotavirus is one of the most common
      diseases in cattle. VP8 portion of the rotavirus VP4 protein is known to contain
      neutralizing epitopes and hemagglutination activity. We expressed the VP8*
      portion of bovine rotavirus strain C486 (G6P1 serotype) in E. coli, and examined
      potential of the recombinant VP8* protein for induction of neutralizing antibody
      responses in host animals. One hundred twenty pregnant beef cows were selected
      and immunized eight weeks prior to parturition with the recombinant VP8* protein.
      Colostral and milk samples were collected 12 hours and 10 days post-calving,
      respectively, and the virus neutralizing titers elicited by the recombinant
      subunit antigen were determined by plaque reduction assay. Colostral antibody
      titres of the vaccinated group were significantly higher than those of the
      unvaccinated control group, and these titers were equivalent to the titers
      elicited by a commercial vaccine. While titers of the control group rapidly
      decreased to 220 after 10 days of calving, neutralizing titers in the milk of the
      vaccinees remained 510. Rabbit and bovine antibodies induced by the recombinant
      VP8* protein were also able to neutralize bovine rotavirus P5 serotype (B641) at
      significant level and P11 serotype (B223) moderately. Our results suggest that
      the E. coli-produced recombinant VP8* protein can be an useful subunit vaccine
      candidate to prevent rotavirus infection in new-born calves.

PMID- 9192048
TI  - Immunoprophylaxis of Salmonella gallinarum infection by Salmonella enteritidis
      immune lymphokines in broiler chicks.
AB  - Research on the control of intestinal and tissue colonization of breeder and
      table-egg producing flocks by invasive Salmonella enteritidis (SE) has focused on
      the advancement of anti-salmonella feed additives, microbiological strategies,
      and the development of vaccines. Recent investigations in our laboratories have
      concentrated on the development of immunoprophylactic measures to control
      Salmonella infections. We have found an increased resistance to Salmonella
      enteritidis (SE) organ infectivity in chickens conferred by the prophylactic
      administration of SE-immune lymphokines (SE-ILK). Fowl typhoid, caused by
      Salmonella gallinarum (SG), is a septicemic disease of domestic birds resulting
      in morbidity with moderate to very high mortality within the first 2 weeks of
      age. The objective of the present studies was to evaluate the effect of a
      prophylactic treatment of neonatal broiler chicks with lymphokines derived from
      S. enteritidis (SE)-immunized chickens (SE-ILK) on the birds' resistance to an
      experimental infection with S. gallinarum (SG). On the day-of- hatch, chicks were
      intraperitoneally administered either SE-ILK, control nonimmune lymphokines
      (NILK), or nothing. Thirty min later, all chicks were gavaged with either 10(4)
      cfu or 10(6) cfu SG. For 10 days after challenge, the chicks were observed twice
      daily for morbidity and mortality. Chicks that died during the experiment had
      their livers cultured for SG. Chicks that survived throughout the 10 day
      experimental period were killed and their livers, spleens, and cecal tonsils
      cultured for SG. The prophylactic treatment of chickens with SE-ILK induced
      significant protection against an extraintestinal SG infections when compared to
      NILK as evidenced by: 1) a significant reduction (P < 0.005) in the mortality of
      chicks challenged with either 10(4) and 10(6) cfu sg; 2) increased average weight
      gains of chicks challenged with either 10(4) and 10(6) efu SG; and 3) a
      significant (P < 0.001) reduction in the total number of SG-organ-culture
      positive chicks. The results suggest that the prophylactic administration of SE
      ILK can non-specifically confer protection to chicks against a pathogenic
      salmonellae as seen by reduced morbidity, mortality, and organ infectivity of SG
      in broiler chicks while enhancing weight gain during the first ten days of life.

PMID- 9192049
TI  - Current concepts of competitive exclusion cultures for the control of salmonellae
      in domestic poultry.
AB  - Two defined competitive exclusion (CE) cultures (CF-I and CF-II) and a
      characterized CE culture (CF-III), which are composed of mixtures of
      nonpathogenic bacteria, were developed from anaerobic continuous-flow (CF)
      cultures that had been inoculated with cecal contents from adult chickens. After
      the primary CF cultures attained homeostasis, 13 bacteria (11 facultative
      anaerobes and 2 obligate anaerobes) representing 6 genera were isolated from CF
      I; II bacteria (9 facultative anaerobes and 2 obligate anaerobes) representing 7
      genera were isolated from CF-II; and 29 bacteria (15 facultative anaerobes and 14
      obligate anaerobes) representing 14 genera were isolated from CF-III. Newly
      hatched chicks were treated orally with each primary CF culture; challenged on
      day 3 with Salmonella typhimurium; and cultured on day 10. Each culture
      significantly (p < 0.05) reduced salmonellae intestinal colonization and organ
      invasion. From the reconstituted CF-I and CF-II cultures, all organisms were
      isolated and their fermentation parameters and efficacy against salmonellae
      challenge were similar, if not identical, to the primary cultures. The CF-I and
      CF-II cultures satisfied the 5 requirements for defined CE cultures: 1) the
      primary CE culture must be efficacious; 2) all bacteria must be isolated and
      identified; 3) the fermentation parameters of the reconstituted CE culture must
      be similar to those of the primary culture; 4) all bacteria from the
      reconstituted culture must be isolated and identified; and 5) the efficacy of the
      reconstituted culture must be very similar to the primary culture. From these
      integrated studies, 3 mechanisms were demonstrated for preventing the enteric
      colonization of salmonellae in newly hatched chicks that were pretreated with CE
      cultures. First, the component organisms in the CE culture establish a normal
      enteric flora prior to salmonellae exposure. Second, the CE organisms compete
      with salmonellae for essential nutrients. Third, the CE organisms produce
      concentrations of volatile fatty acids at low pH levels that are bacteriostatic
      for salmonellae.

PMID- 9192050
TI  - Selection of swine resistant to F4-positive Escherichia coli.

PMID- 9192051
TI  - Hemagglutinin-esterase glycoprotein gene of bovine corona virus delivered by
      adenovirus vector induces mucosal immunity in cotton rats.

PMID- 9192052
TI  - Role of metabolic products produced by competitive exclusion cultures for the
      control of salmonellae in domestic poultry.

PMID- 9192053
TI  - Two UK Government proposals bearing on drug safety.

PMID- 9192054
TI  - Paracetamol.

PMID- 9192055
TI  - The effects of alcohol on the heart.
AB  - We have discussed in this review many features and possible mechanisms
      responsible for the development of alcoholic cardiomyopathy. The evidence
      suggests that defects in myofibrillar protein turnover occur in both acute and
      chronic alcohol studies. Possible mechanisms to explain poor contractile function
      include alterations in cellular calcium, magnesium or phosphate homeostasis. The
      toxic effects of acetaldehyde or the formation of fatty acid ethyl esters may
      cause impairment of mitochondrial oxidative phosphorylation. Alternatively,
      reduced amounts of heat shock proteins may result in poor assembly and protection
      of proteins. In acute ethanol toxicity ischaemia may occur, possibly due to
      increased xanthine oxidase activity or beta-adrenergic stimulation. Chronic
      alcohol consumption can also lead to the development of hypertension via
      magnesium loss and consequent alterations in peripheral vascular calcium
      regulation. However, these are only a few facets of a complex relationship
      between alcohol and the cardiovascular system.

PMID- 9192056
TI  - Methaemoglobinaemia.

PMID- 9192057
TI  - Ulcerative colitis: a genetic disease?
AB  - A number of lines of evidence support the hypothesis that ulcerative colitis is
      an inherited disorder in a proportion of cases. First, there is a pattern of
      familial aggregation. Second, there are differences in the prevalence of the
      disease in different ethnic groups. Finally, the concordance rate in monozygotic
      twin pairs is higher than that of dizygotic twin pairs, although not as high as
      the concordance rates observed in Crohn's disease. Genetic models of the
      inheritance patterns suggest that ulcerative colitis is probably caused by one
      major gene, although that gene (or genes) remains to be identified. While at
      least one localization for susceptibility to Crohn's disease now seems certain,
      efforts to localize and characterize the susceptibility genes involved in the
      inheritance of ulcerative colitis are still underway. While the genes of the
      major histocompatibility complex have been imputed as causal in susceptibility to
      ulcerative colitis, a consensus of proof continues to elude us.

PMID- 9192058
TI  - Ulcerative colitis: an epithelial disease?
AB  - There is now considerable evidence that abnormalities of the structure and
      function of the colonic epithelium are present in patients with ulcerative
      colitis and that many of these may occur independently of mucosal inflammation.
      It is proposed that epithelial abnormalities are the central defect that underlie
      the development of mucosal inflammation and its chronicity. A simple model for
      pathogenesis is proposed in which inflammation develops only when epithelial
      barrier function is impaired to an extent which permits the influx of luminal pro
      inflammatory molecules to the lamina propria. Several candidate hypotheses
      regarding the molecular basis for the abnormality are addressed. The mechanism by
      which the barrier function is critically impaired involves the interaction of the
      abnormal epithelium with luminal, mucosal and systemic factors. Focusing on the
      epithelium would potentially lead to a conceptually different management approach
      and the development of novel therapeutic strategies.

PMID- 9192059
TI  - Ulcerative colitis: an immunological disease?
AB  - Ulcerative colitis is an inflammatory disease of the large intestine of unknown
      aetiology. The nature of the inflammatory infiltrate together with the response
      to corticosteroids suggests that an abnormal immune response is at work. The key
      question of whether the immune system is responding to an abnormal breach in the
      mucosa due to another primary abnormality or whether the primary defect lies
      within the immune response itself has not been answered. Thus far, it is clear
      that both T and B cell compartments are involved in the persistence of
      inflammation but the initial interactions that take place in the mucosa in terms
      of antigen processing and presentation have not been adequately investigated.
      Those critical steps and potential defects that push T cells and B cells into a
      heightened state of activation need to be identified.

PMID- 9192060
TI  - The natural history of ulcerative colitis.
AB  - The majority of patients with ulcerative colitis (UC) will run a typical chronic,
      relapsing course. The proportion with chronic, continuous symptoms diminishes
      with time. The greatest impact of the disease is in the first few years after
      diagnosis, especially in patients with extensive or severe colitis. After this
      time, the likelihood of requiring surgery declines rapidly, and survival is no
      different from that of the general population. The long-term course can be best
      predicted by the course in the preceding period. Most patients are able to lead
      an essentially normal lifestyle, at work and at home, with either medical or
      surgical treatment. Awareness of how the patient feels the disease affects his or
      her life is important. Educating the patient about their illness will also help
      in management.

PMID- 9192061
TI  - Colonoscopy and biopsy.
AB  - The place of colonoscopy in the management of ulcerative colitis is restricted to
      clinical situations where the information provided will change clinical
      management. The information provided will be answers to the
      questions?inflammatory bowel disease, o r, in the patient with known colitis:
      inflammatory bowel disease?type?activity extent?dysplasia. Biopsy is pivotal to
      the diagnosis and provides the certainty of tissue diagnosis, assessment of
      activity and detection of dysplasia. Sigmoidoscopy is sufficient for providing
      information for clinical management in most circumstances, but colonoscopy is
      important where clinical features are disproportionate to sigmoidoscopic findings
      and systemic parameters of inflammatory activity; to determine type and extent of
      inflammatory bowel disease and when surveillance needs to start; and for biopsy
      to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for
      differential diagnosis, and is the unique definer of total colonoscopy.

PMID- 9192062
TI  - Investigation of the patient with abnormal liver function tests.
AB  - About one-half of patients with ulcerative colitis develop abnormal liver
      function tests at some time during the course of the illness. This should prompt
      an investigation for primary sclerosing cholangitis and other common
      hepatobiliary diseases. Primary sclerosing cholangitis occurs in 2-10% of
      patients with ulcerative colitis. The diagnosis of primary sclerosing cholangitis
      is most often made by endoscopic retrograde cholangiography. Liver histopathology
      is often inconclusive but magnetic resonance cholangiography shows promise as a
      useful non-invasive diagnostic tool. Cholangiocarcinoma complicates 20-40% of
      patients with end-stage primary sclerosing cholangitis and is now one of the most
      common causes of death in patients with ulcerative colitis. Distinction between
      benign and malignant strictures can be difficult and is best done with a
      combination of clinical suspicion, repeated imaging for mass lesions,
      cholangiography, and endoscopic brushings and/or biopsies. Dominant lesions of
      the common bile duct or common hepatic duct produce progressive jaundice and
      liver damage. Early treatment may improve prognosis. Single strictures can be
      dilated endoscopically. If the stricture is more complicated and extends into the
      intrahepatic ducts or there is suspicion of cholangiocarcinoma, surgical
      resection may be more appropriate. Liver transplantation should be considered in
      end-stage disease.

PMID- 9192063
TI  - Innovations in topical therapy.
AB  - Topical therapy can be considered the standard treatment for distal ulcerative
      colitis. The group of drugs of first choice are the aminosalicylates which are
      effective in inducing remission in acute disease as well as in preventing
      relapse. Corticosteroids appear to be slightly less effective and have no proven
      benefit in maintenance therapy. With new topical steroids, such as budesonide,
      systemic effects can be minimized. The major role of corticosteroids is to
      complement aminosalicylates, when necessary. The new topical compounds appear to
      be especially valuable when there is a long-term requirement for corticosteroids.
      With the vast majority of patients obtaining remission with standard treatment,
      it is difficult to make the case for alternative substances. Short-chain fatty
      acids, local anaesthetics and bismuth compounds seem to be the most promising
      innovations in topical therapy although their equivalence or even superiority to
      mesalazine has not been established.

PMID- 9192064
TI  - Safety of corticosteroids and immunosuppressive agents in ulcerative colitis.
AB  - For many years, corticosteroids have been the mainstay for treating acute
      ulcerative colitis. In patients with refractory disease, immunosuppressive
      therapy may be indicated, including azathioprine or its metabolite 6
      mercaptopurine, cyclosporin and possibly methotrexate. Their benefits in
      ulcerative colitis must be weighed up against their possible adverse effects, the
      availability of surgical cure for this condition, and the long-term risk of
      carcinoma complicating colitis that applies in patients with chronic extensive
      disease. Information about the safety of corticosteroids and immunosuppressive
      agents has accumulated as a result of their extensive use in inflammatory bowel
      disease, organ transplantation and various other disorders.

PMID- 9192065
TI  - Management of the first presentation of severe acute colitis.
AB  - Prompt diagnosis and exclusion of infection requires a minimum of rigid
      sigmoidoscopy, rectal mucosal biopsy and stool culture. Admission to hospital is
      mandatory for patients with features of severe disease, or who are in their first
      attack of ulcerative colitis and have bloody diarrhoea, even if the criteria for
      severe disease are not met. Once admitted, the patient should be monitored by
      plain abdominal X-ray, full blood count, serum albumin and C reactive protein on
      alternate days; temperature and pulse rate should be recorded four times per day.
      Treatment should be instituted as soon as the diagnosis is made with an
      intravenous corticosteroid (hydrocortisone 100 mg intravenously, four times
      daily, or equivalent). Antibiotics may be included if infection cannot be
      confidently excluded. Free diet can be allowed but attention should be given to
      nutritional, fluid and electrolyte status with intravenous replacement if
      necessary. Any evidence of colonic dilatation occurring despite maximal therapy
      should be regarded as an absolute indication for colectomy. The patient should be
      kept fully informed from an early stage about the likely natural history of the
      condition and about the possible therapeutic options including surgery.
      Cyclosporin therapy should be reserved for patients who have a poor response to
      the first 3-4 days of corticosteroid therapy, particularly those with serum C
      reactive protein > 45 mg/l and who do not yet have absolute indications for
      colectomy. Most patients who have not convincingly responded within 10 days of
      starting full medical therapy should undergo colectomy, although partial
      responders who are afebrile may reasonably continue for up to 14 days before a
      final decision. Approximately 30-40% of patients with severe colitis will need
      colectomy within the first 6 months. With optimal management, mortality should be
      zero, but better medical therapies are urgently needed to reduce the colectomy
      rate.

PMID- 9192066
TI  - Nutrition and ulcerative colitis.
AB  - The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC)
      remains uncertain. Impaired utilization by colonocytes of butyrate, a product of
      bacterial fermentation of dietary carbohydrates escaping digestion, may be
      important. Sulphur-fermenting bacteria may be involved in this impaired
      utilization. Oxidative stress probably mediates tissue injury but is probably not
      of causative importance. Patients with UC are prone to malnutrition and its
      detrimental effects. However, there is no role for total parenteral nutrition and
      bowel rest as primary therapy for UC. The maintenance of adequate nutrition is
      very important, particularly in the peri-operative patient. In the absence of
      massive bleeding, perforation, toxic megacolon or obstruction, enteral rather
      than parenteral nutrition should be the mode of choice. Nutrients may be
      beneficial as adjuvant therapy. Butyrate enemas have improved patients with
      otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre
      supplements are of benefit in rats with experimental colitis. Eicosapentaenoic
      acid in fish oil has a steroid-sparing effect which, although modest, is
      important, particularly in terms of reducing the risk of osteoporosis, but it
      seems to have no role in the patient with inactive disease. gamma-Linolenic acid
      and anti-oxidants also are showing promise. Nutrients may also modify the
      increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA
      but there are no data published at present on possible protection from oral anti
      oxidants. Butyrate protects against experimental carcinogenesis in rats with
      experimental colitis. Folate supplementation is weakly associated with decreased
      incidence of cancer in UC patients when assessed retrospectively. Vigilance
      should be maintained for increased micronutrient requirements and supplements
      given as appropriate. Calcium and low-dose vitamin D should be given to patients
      on long-term steroids and folate to those on sulphasalazine.

PMID- 9192067
TI  - Ileal pouches: adaptation and inflammation.
AB  - Ileal pouch-anal anastomosis (IPAA) has become the operation of choice following
      proctocolectomy for ulcerative colitis (UC) and familial adenomatous polyposis.
      Functioning ileal pouch mucosa undergoes histological changes resembling the
      colon (colonic metaplasia). The possible role of stasis and luminal factors--bile
      acids, short-chain fatty acids and bacteria--are discussed. It seems likely that
      colonic metaplasia is an adaptive response to the new luminal environment in
      IPAA. Inflammation in the ileal reservoir ('pouchitis') is the most significant
      late complication in IPAA. It occurs in 20-30% of patients and is virtually
      confined to those with prior UC. The clinical picture in pouchitis is highly
      variable; however, it can be easily categorized into three groups. Nevertheless,
      in most cases it is likely to represent recurrent UC in the ileal pouch. Current
      treatments and possible preventative strategies for pouchitis have been outlined.

PMID- 9192068
TI  - NMR methods for the study of protein structure and dynamics.
AB  - An understanding of the role played by a protein in cellular function requires a
      detailed picture of its three-dimensional structure as well as an appreciation of
      how the structure varies as a function of time as a result of molecular dynamics.
      Over the past several years, multidimensional, multinuclear solution NMR
      spectroscopy has become a powerful technology for obtaining both structural and
      dynamical information on proteins and protein-ligand systems. In the present
      review, a number of new methodological advances are highlighted that have
      significantly improved the quality of NMR spectra of biomolecules and have
      increased the molecular weight limitations previously imposed on NMR-based
      structural studies of macromolecules. Applications of this technology to a number
      of protein systems currently studied in my laboratory are presented.

PMID- 9192069
TI  - Protein phosphatases: structures and implications.
AB  - Protein phosphatases are signal transducing enzymes that dephosphorylate
      intracellular proteins phosphorylated on serine, threonine, and tyrosine
      residues. This brief review surveys recently determined structures of members of
      the protein tyrosine phosphatase and protein serine/threonine phosphatase
      families. In each family, characteristic and distinct structures confer different
      enzymatic mechanisms in catalyzing dephosphorylation reactions. Within each
      family, however, there exists remarkable similarity in active-site conformation
      and catalytic mechanism despite, in some cases, little or no sequence homology.
      The crystal structures also provide the basis for understanding the substrate
      binding specificity, inhibition by physiologically relevant compounds, and
      regulation of the protein phosphatases.

PMID- 9192070
TI  - Activation of protein kinase C during newt limb regeneration: effect of
      denervation.
AB  - Blastema cell proliferation during newt limb regeneration is a nerve-dependent
      process. The present study was undertaken to determine whether or not that
      process is mediated by protein kinase C (PKC) activation during limb regeneration
      in Pleurodeles walt. Analysis included evaluation of PKC activity and its
      subcellular localization at various stages of regeneration, both in vivo and in
      vitro. The data reveal an increase in PKC activity in both the cytosol and
      particulate fractions of whole blastemas reaching a maximum at the mid-bud stage,
      which correlates with blastema cell proliferation rate. Denervation significantly
      reduces blastema cell proliferation and also causes a reduction in membrane
      associated PKC activity. The effect of PKC activity appears to be restricted to
      the blastemal mesenchyme, which exhibits a dramatic reduction in activity 96 h
      after denervation. In contrast, PKC activity in the epidermal cap did not change.
      Cultured whole blastemas likewise express a decrease in particulate PKC activity
      and therefore mimic denervated blastemas in this parameter. Co-culture of
      blastemas with spinal ganglia partially reduces the decline in PKC activity, and
      the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, a direct activator of
      PKC, also prevents the fall in membrane-bound PKC activity while stimulating
      blastema cell proliferation, in vitro. These data indicate that blastema cell
      (mesenchyme) proliferation is related to increased PKC activity and that PKC may
      therefore be involved in the nerve-dependent signalling pathway regulating the
      early phase of urodele limb regeneration.

PMID- 9192071
TI  - Modulation and phosphorylation of calbindin-D28K correlates with protein kinase C
      activation1.
AB  - Calbindin-D28K is a vitamin D3 dependent calcium-binding protein expressed in
      renal distal tubules. We previously reported that 24 h treatment with 1 alpha, 25
      dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D3, induces calbindin
      D28K and activates protein kinase C (PKC) in MDBK (Madin-Darby bovine kidney)
      cells. In contrast, 24 h treatment with the phorbol ester 12-O
      tetradecanoylphorbol-3-acetate (TPA) downregulates calbindin-D28K and PKC
      activity. In the present studies, we demonstrate that TPA rapidly enhances
      calbindin-D28K expression in MDBK cells in the absence of 1,25-D3. The
      enhancement of calbindin-D28K expression is preceded by activation and
      translocation of PKC alpha. Further, we show that PKC directly phosphorylates
      calbindin-D28K in a calcium- and phospholipid-dependent manner in vitro. In MDBK
      cells, the calbindin-D28K antibody immunoprecipitates a 28 kDa protein for which
      phosphorylation is enhanced after treatment for 1 h with TPA or 24 h with 1,25
      D3. Consistent with amino acid sequence analysis of calbindin-D28K indicating two
      threonine residues that fit the consensus for PKC phosphorylation, TPA-treated
      MDBK cells exhibit enhanced expression of a phosphothreonine-containing protein
      that co-migrates with calbindin-D28K. These studies offer the first report that
      calbindin-D28K is a phosphoprotein and implicate the PKC signal transduction
      pathway in its regulation.

PMID- 9192072
TI  - Effects of acute and chronic hindlimb suspension on sensitivity and
      responsiveness to insulin in the rat soleus muscle.
AB  - The effects of acute (24 h) and chronic (5 weeks) hindlimb suspension on insulin
      stimulated glucose utilization by the rat soleus muscle were studied in vitro.
      Hindlimb suspension resulted in an enhancement of basal glucose transport,
      lactate production, and glycogen synthesis. An increase in the sensitivity of
      these processes to insulin occurred as early as 24 h and persisted for 5 weeks of
      the muscle unloading. An increased responsiveness to insulin was found only for
      glucose transport after 24 h. The present data do not support the concept that
      the enhanced glucose utilization and improved muscle insulin sensitivity during
      hindlimb suspension are related to muscle atrophy, which is not observed in the
      early stage of muscle unweighting.

PMID- 9192073
TI  - Bacterial overexpression, isotope enrichment, and NMR analysis of the N-terminal
      domain of human apolipoprotein E.
AB  - The nucleotide sequence encoding the N-terminal domain (residues 1-183) of human
      apolipoprotein E3 (apoE3) was cloned into the pET expression vector and
      introduced into Escherichia coli. Induction of protein expression with isopropyl
      beta-D-thiogalactopyranoside resulted in production of recombinant apoE3(1-183).
      Immunoblot analysis revealed that recombinant protein was present in both the
      cell pellet and cell culture supernatant. Analysis revealed that a significant
      portion of the rApoE3(1-183) in the cell pellet still possessed the bacterial N
      terminal pel B leader sequence, encoded by plasmid DNA directly upstream of the
      apoE3(1-183) coding sequence. By contrast, this hydrophobic leader sequence had
      been removed from recombinant protein specifically accumulating in the culture
      medium. This behavior is novel for bacterial expression of apolipoprotein E and
      its truncated variants and permits efficient overexpression of the recombinant
      protein (> 100 mg/L cell culture). Recombinant apoE3(1-183) was isolated by a
      combination of heparin-Sepharose chromatography and reverse-phase HPLC.
      Electrospray mass spectrometry provided a mass of 21 191 daltons, corresponding
      directly to that expected from the known sequence. Circular dichroism
      spectroscopy revealed that the recombinant protein possesses significant amounts
      of alpha-helical secondary structure. The lipid binding ability of rApoE3(1-183)
      was evaluated using an in vitro lipoprotein binding assay. It was observed that
      recombinant apoE3(1-183) protected human low density lipoprotein (LDL) from lipid
      accumulation induced particle aggregation, indicating that it is capable of
      associating with lipoprotein surfaces. In addition, rApoE3(1-183) forms disk
      complexes with the model phospholipid dimyristoylphosphatidylcholine. In
      competition experiments, it was observed that rApoE3(1-183) phospholipid disks
      compete with 125I-LDL for binding to the apoB/E receptor on human skin
      fibroblasts to an extent similar to that observed for intact rApoE3. Taken
      together, these data show that recombinant apoE3(1-183) is fully functional as an
      apolipoprotein and receptor ligand. Given the high expression level and its known
      existence as a monomer in solution, we evaluated the potential for application of
      NMR spectroscopy to study the structure-function relationship of rApoE3(1-183).
      Bacteria were cultured in media supplemented with 15NH4Cl or [15N]glycine and the
      isotopically labeled recombinant apoE3(1-183) was analyzed by heteronuclear
      single quantum correlation NMR spectroscopy. The data revealed that rApoE3(1-183)
      is an excellent candidate for solution structure studies by NMR, including
      conformational adaptations associated with lipid association.

PMID- 9192074
TI  - Detection of an unfolding intermediate in alpha-urease with enhanced affinity for
      ANSA.
AB  - Protein aggregation is believed to be due to conformers that expose hydrophobic
      clusters that promote protein association. Such conformers can be detected using
      a fluorescent probe like 8-anilino 1-naphthalenesulfonic acid (ANSA). Here we
      show that urease exposed to 1.0 M guanidine-hydrogen chloride has a higher
      affinity for ANSA that native or denatured urease. The binding occurs over a
      narrow range of denaturant concentration, well below the concentration required
      to induce denaturation. The impact of ANSA on urease aggregation was further
      studied by fluorescence, light-scattering, and activity measurements. We found
      that ANSA modifies urease aggregates and can provide partial protection against
      inactivation arising from thermally induced aggregation. It seems that the well
      known susceptibility of urease to aggregation is due to an intermediate that can
      be populated in the absence of denaturation. Such a rationale would explain why
      folding stability of urease is a poor indicator of long-term stabilization by
      various media.

PMID- 9192075
TI  - Essential arginine residues in isoprenylcysteine protein carboxyl
      methyltransferase.
AB  - We used specific amino acid modifying reagents to characterize the
      isoprenylcysteine carboxyl methyltransferase in kidney membranes. The enzyme was
      inactivated by reagents specific for arginine, histidine, cysteine, and
      tryptophan residues. Protection by the product and inhibitor S-adenosyl-L
      homocysteine was observed for arginine modification by phenylglyoxal and
      tryptophan modification by N-bromosuccinimide. We focused on modification by
      phenylglyoxal, a highly specific modifier of arginine residues. The inactivation
      of methyltransferase by phenylglyoxal follows pseudo-first-order kinetics and the
      order of the reaction, n, with respect to phenylglyoxal was 1.2. The inactivation
      increased with the alkalinity of the preincubation medium and was maximal at pH
      10. Kinetic analysis showed that the K(m) for S-adenosyl-L-methionine is not
      significantly affected by treatment with phenylglyoxal but that the Vmax is
      reduced p-Hydroxyphenylglyoxal, a more hydrophilic derivative of phenylglyoxal,
      was a less potent inactivator of methyltransferase than phenylglyoxal, suggesting
      that arginine residues modified are in a hydrophobic environment. The
      methyltransferase is protected from phenylglyoxal modification by S-adenosyl-L
      homocysteine but not S-adenosyl-L-methionine, sinefungin, N-acetyl-S-farnesyl-L
      cysteine, or farnesylthioacetate. The arginine residue modified may thus be
      located either at the active site or at another additional binding site for S
      adenosyl-L-homocysteine. These results indicate that arginine residues are
      essential for the enzymatic activity of isoprenylcysteine carboxyl
      methyltransferase.

PMID- 9192076
TI  - Ligation, inhibition, and activation of cytochrome c oxidase by fatty acids.
AB  - Free fatty acids bind to beef heart cytochrome c oxidase and induce spectral
      shifts similar to those obtained with high spin ligands. Oleic (18:1(n-9)) and
      linoleic (18:2(n-6)) acids induce substantial blue shifts of the Soret peak of
      oxidized enzyme. Small saturated fatty acids (< 15 carbon atoms) shift the Soret
      peak to the red, and longer chain acids induce smaller blue shifts. Formate
      induced spectral shifts are modified by short chain fatty acids but are
      unaffected by longer chain fatty acids for which effects are additive with those
      of formate. Inhibition by formate is partially relieved by all fatty acids
      tested. Palmitic and linoleic acids increase turnover at low cytochrome c levels
      and decrease the K(m) for cytochrome c at high cytochrome c levels. Oleic acid
      protects the enzyme against acid denaturation during turnover. Bovine serum
      albumin produces a red shift in the oxidase Soret peak and inhibits turnover of
      the isolated enzyme. Oleic acid and serum albumin modify the electron
      paramagnetic resonance spectrum of oxidized oxidase, oleic acid shifting the g =
      3 (cytochrome a) peak towards low field and albumin towards higher field
      strengths. The oxidase may possess at least two fatty acid binding sites at one
      of which cytochrome c binding is modulated and at another spectral changes may be
      induced. One site is close enough to the binuclear centre to interact
      allosterically with ligand binding at that centre.

PMID- 9192077
TI  - No mechanical role for vinculin in strain transduction in primary bovine
      osteoblasts.
AB  - Vinculin is thought to play a central role in linking the actin cytoskeleton to
      the integrin adhesion proteins of focal contacts and also in cell-cell adhesion
      sites. We have investigated aspects of attachment and the transduction of
      mechanical stimulation on the function of vinculin and its assembly in primary
      bovine osteoblasts. The dynamic attachment process was concomitant with the
      reassembly of vinculin from a soluble cytoplasmic pool into Triton-insoluble
      focal adhesions. Immunoblotting experiments demonstrated a slight increase in the
      amount of vinculin concentrated in focal contacts that was paralleled by a
      discrete decrease in the Triton-soluble fraction of cytoplasmic vinculin. Sixty
      cycles of 1 Hz deformations at 0.02% (hypophysiological, no change in cell
      division rate), 0.2% (within the normal physiological range), and 1%
      (hyperphysiological) resulted in a rapid and reversible disassembly of vinculin
      from focal contacts to a homogeneous cytoplasmic localization, although
      alterations in the shape and morphology of cells could not be detected. Although
      all mechanical loading protocols dramatically depleted vinculin from focal
      contacts, its initial distribution in adhesion plaques was fully restored within
      the next 60 min, demonstrating the highly dynamic and reversible shift of this
      protein from a membrane-associated pool to the cytoplasm. By first depleting
      vinculin from the focal adhesion sites by applying 0.02% strain, waiting 60 s,
      and then applying 0.2% strain, we show that the transduction of mechanical
      deformation was identical with controls that had not been pretreated. This
      indicates that vinculin does not play a role in mechanical transduction, that
      significant mechanical forces are not transmitted through vinculin, and also that
      loss of vinculin at the focal adhesion site does not have significant effects, in
      the short term, on cell adhesion.

PMID- 9192078
TI  - epsilon(gamma-Glutamyl)lysine crosslinks are concentrated in a non-collagenous
      microfibrillar fraction of cartilage.
AB  - Fractions of rib cartilage were obtained by homogenization and extracted with 4 M
      guanidinium chloride, and the washed residue was digested with purified
      collagenase. Differential centrifugation of the insoluble residue from this
      digestion yielded a non-collagenous fraction that earlier work had shown to
      contain microfibrils. This material contains a much higher concentration of
      epsilon(gamma-glutamyl)lysine than the ribs or any of the other cartilage
      fractions. This transglutaminase-derived crosslink may be a common component of
      extracellular matrix microfibrils.

PMID- 9192079
TI  - Substances in the aqueous fraction of cigarette smoke inhibit lipid peroxidation
      in synaptosomes of rat cerebral cortex.
AB  - The effects of water-soluble substances in cigarette smoke on lipid peroxidation
      were investigated using nerve terminals prepared from the rat cerebral cortex.
      The prepared smoke-substances significantly reduced the spontaneous increase in
      thiobarbituric acid-reactive substances in synaptosomes in a dilution factor
      dependent manner. Furthermore, the aqueous extract also inhibited the elevation
      of lipid peroxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride,
      a peroxyl radical generator. Smoke-substances scavenged superoxide radicals
      generated from stimulated human leukocytes and from the xanthine/xanthine oxidase
      system. These effects were not mimicked by nicotine. The antioxidant effects of
      smoke-substances were preserved for several days at 5 degrees or -80 degrees C.
      The results suggest that the smoke-substances may possess long half-lives and
      scavenge the radicals which cause lipid-peroxidation in synaptosome membranes.

PMID- 9192080
TI  - Protein involvement in thermally induced structural transitions of pig
      erythrocyte ghosts.
AB  - Thermal transitions in pig erythrocyte ghosts were studied by differential
      scanning calorimetry and thermal gel analysis (TGA). Heating of the suspension of
      pig erythrocyte ghosts induced at least six thermodynamically irreversible
      transitions. Each of these transitions is believed to be due to a localized
      structural transition induced by thermal stress. Using TGA and covalent
      attachment of the anionic transport inhibitor regions in the thermograms
      corresponding to the heat sorption of some proteins of the pig erythrocyte ghosts
      were identified.

PMID- 9192081
TI  - Functioning of oligomeric-type light-harvesting antenna.
AB  - In our previous work, we developed, for the first time, a theory of excitation
      energy transfer within an oligomeric-type light-harvesting antenna and, in
      particular, within the chlorosome of green bacteria (Biophys.J., 1996, vol.71,
      pp.995-1010). The theory was recently developed for a new original exciton model
      of aggregation of chlorosomal pigments, bacteriochlorophylls (BCh1) c/d/e
      (Biochem, Mol.Biol.Int., 1996, vol.40, No.2, pp. 243-252). In this paper, it was
      demonstrated with picosecond fluorescence spectroscopy that this theory explains
      the antenna-size-dependent kinetics of fluorescence decay in chlorosomal antenna,
      measured for intact cells of different cultures of the green bacterium Chlorobium
      limicola with different chlorosomal antenna size determined by electron
      microscopic examination of the ultrathin sections of the cells. According to our
      model, the energy transfer dynamics within the chlorosome imply the formation of
      a cylindrical exciton, delocalized over a tubular aggregate of BCh1 c chains, and
      inductive-resonance-type transfer of such a cylindrical exciton between the
      nearest tubular BCh1 c aggregates and to BCh1 a of the chlorosome.

PMID- 9192082
TI  - ATP/ADP antiporter- and aspartate/glutamate antiporter-mediated fatty acid
      induced uncoupling of liver mitochondria in incubation media differing in ion
      composition.
AB  - Substitution of potassium cloride for sucrose in the incubation medium of liver
      mitochondria or addition of magnesium cloride to the sucrose medium produces a
      small (if any) effect on the palmitate-induced uncoupling and its sensitivity to
      carboxyatractylate and aspartate, but it exerts a pronounced increase in the
      recoupling effect of glutamate on this uncoupling. 20-40 microM cetyltrimethyl
      ammonium bromide increases the recoupling effect of glutamate and aspartate but
      decreases that of carboxyatractylate. The data are in line with suggestion that
      both ATP/ADP antiporter and aspartate/glutamate antiporters are involved in the
      fatty acid-induced uncoupling.

PMID- 9192083
TI  - Hydroxyl and superoxide anion radical scavenging activities of natural source
      antioxidants using the computerized JES-FR30 ESR spectrometer system.
AB  - Free radical scavenging activities of water-soluble extracts from some natural
      sources, health foods, and antioxidant substances were measured using the JES
      FR30 JEOL spectrometer. The objective was to develop a standardized method
      whereby comparison could be made between the radical scavenging activities of
      complex mixtures. Scavenging of hydroxyl radical was determined using DMPO.
      Activity was calibrated using a standard material, L-ascorbic acid 2-[3,4-dihydro
      2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen
      phosphate] potassium salt (EPC-K1), an analog of vitamin C and vitamin E which is
      water soluble and stable at room temperature. The order of greatest hydroxyl
      radical scavenging activity was green tea extract, pine bark extract
      (Pycnogenol), Ginkgo Biloba extract (EGb 761), a flavonoid blend of several fruit
      and vegetable extracts (GNLD), and Bio-Normalizer (Sun-O Corp). Activity was
      determined after treatment of samples with ascorbic acid oxidase. This treatment
      revealed the presence of ascorbate in some natural extracts and commercial
      preparations. The pine bark extract was the most heat resistant and had ascorbate
      like activity in the preparations. Scavenging of superoxide anion was determined
      using the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and analyzed by
      comparison with a standard curve made with superoxide dismutase. Comparison of
      the water solubilized components of natural source antioxidants showed that
      filtrates fractionated using centrifuge type Millipore filter tubes (M.W. <
      100,000; M.W. < 10,000) also had almost the same SOD-like activity. Samples were
      also treated with ascorbate oxidase or by heating (100 degrees C for 10 min). The
      order of activity, from greatest to least, was Ginkgo biloba extract EGb 761,
      pycnogenol, beta-catechin, tea and BioNormalizer.

PMID- 9192084
TI  - Evaluation of antisense inhibition in a B cell model.
AB  - An in vitro model has been developed in an attempt to optimise antisense
      inhibition in B cells as a prelude to transgenic studies. The hypotheses tested
      were that i) the 3'-untranslated region would be an appropriate target for
      antisense inhibition; 2) the immunoglobulin heavy chain intronic enhancer could
      be used to enhance antisense inhibition via increased production of antisense
      transcripts; and 3) the mouse metallothionein-1 promoter would allow induction of
      antisense inhibition in B cells. Secreted IgM protein and mRNA were monitored
      following the stable transfection of a B cell line, HO-2.2, with a series of
      plasmid constructs containing antisense or sense target sequence DNA under the
      control of either the mouse metallothionein-1 promoter or homologous (ie same
      promoter as target sequence) immunoglobulin heavy chain promoter. The 3'
      untranslated region proved to be an appropriate target resulting in 70%
      inhibition of IgM secretion. Compared with untransfected and sense controls,
      significant decreases in IgM secretion (and RNA levels) were detected in clones
      transfected with antisense constructs utilising the mouse metallothionein-1
      promoter and the immunoglobulin heavy chain intronic enhancer elements. These
      clones exhibited a further significant reduction in secreted IgM production upon
      zinc induction. Hybridisation studies demonstrated that decreased protein
      production was most likely attributable to reduction in RNA levels. In contrast,
      transfection with antisense constructs had no effect on membrane IgM protein
      levels which not only confirmed the specificity of antisense action but meant
      that the B cell remained sensitive to receptor ligation. We conclude that
      reasonable antisense inhibition of gene product expression can be achieved in B
      cells by targeting the 3'-untranslated region and using both an inducible
      promoter (mouse metallothionein-1) and the IgH enhancer to aid antisense RNA
      production.

PMID- 9192086
TI  - Mouse deoxyribonuclease I (DNase I): biochemical and immunological
      characterization, cDNA structure and tissue distribution.
AB  - Mouse urinary deoxyribonuclease I (DNase I) resembles rat and human DNase Is in
      terms of its proteochemical and enzymological properties. Furthermore, mouse
      DNase I was demonstrated to be immunologically closer to the rat than to the
      human enzyme. A 1176 bp full length cDNA encoding mouse DNase I was constructed
      from RNA obtained from the kidney and parotid glands. The amino acid sequence up
      to the 45th residue from the N-terminal of the mature enzyme was identical to
      that deduced from the cDNA sequence. This DNase I was distributed most densely in
      the parotid glands from the standpoint of both enzyme activity and gene
      transcript levels.

PMID- 9192085
TI  - Nanomolar concentrations of gangliosides stimulate primary humoral response.
AB  - Exogenous gangliosides act as immunosuppressors when applied at micromolar
      concentrations corresponding to their average level in human plasma. Here we show
      that at nanomolar concentrations the gangliosides GD3, GD1a and GM1 can act as
      immunostimulators markedly enhancing the number of plaque-forming cells in mouse
      splenocyte culture responding to sheep erythrocytes. At such low concentration
      these gangliosides as well as GM3 were not able to influence significantly
      proliferative responses of splenic B and T lymphocytes or of cytotoxic T-cells.
      Neither did they change significantly the production of IL-1 by antigen-
      representing cells, or of IL-2 by Con A-induced blasts in the splenocyte culture.
      It is suggested that the stimulatory effect of low ganglioside concentrations on
      humoral response is due to their influence on cooperative cell-cell interactions
      required for the differentiation of B-cells into Ig-secreting cells.

PMID- 9192087
TI  - Binding of the bovine caseinoglycopeptide to the platelet membrane glycoprotein
      GPIb alpha.
AB  - The bovine caseinoglycopeptide (residues 106-169), the C-terminal part of kappa
      casein, inhibited the von Willebrand factor-dependent platelet aggregation in a
      dose-dependent manner. An affinity matrix made of the caseinoglycopeptide
      selectively bound the platelet membrane glycoprotein GPIb alpha which contains
      the von Willebrand factor binding site. The amino acid residues of GPIb alpha
      participating in the caseinoglycopeptide binding were located after residue Glu
      90.

PMID- 9192088
TI  - cDNA sequence analysis of cardiotoxin variants from Taiwan cobra.
AB  - Five cDNAs encoding cardiotoxin variants were constructed from the cellular RNA
      isolated from the venom glands of Naja naja atra by reverse transcription
      polymerase chain reaction. A high degree of nucleotide sequence homology was
      observed between these variants and other determined ones. Among them, a novel
      cardiotoxin 6 had 61 amino acid residues rather than 60 ones that usually
      observed with Naja naja atra cardiotoxins. The other cardiotoxin variants were
      the homologues of cardiotoxins 1, V or N with one or two amino acid
      substitutions, respectively. These results probably reflect the involvement of
      RNA editing in the production of cardiotoxin variants in the venom of Taiwan
      cobra.

PMID- 9192089
TI  - Enhanced in vivo catalytic activity of PEG-modified cellulase complex from
      Trichoderma reesei.
AB  - The cellulase complex from Trichoderma reesei was polyethylene glycol (PEG)
      modified with considerable retention of endo-beta-1,4-glucanase activity, as
      evaluated by the carboxymethylcellulase (CMCase) assay. While resistance towards
      heat denaturation was the same for either form, susceptibility towards
      proteolysis was slightly greater for the PEG-conjugate, in contrast to most
      reports using other enzymes. The circulatory life of endoglucanase activity
      associated with the complex was enhanced upon PEG-modification. This was
      confirmed by demonstrating degradation of chromogen-labelled substrate injected
      (i.v.) after 24hr of administration of the PEG-ylated enzymes; in contrast the
      substrate remained undegraded in mice pretreated with the native complex. The PEG
      modified complex could be a good candidate for the treatment of pneumoconioses of
      textile workers exposed to cotton dust.

PMID- 9192090
TI  - dl-propranolol negatively regulates the transcription of proliferating cell
      nuclear antigen (PCNA)-gene and thereby suppresses DNA synthesis in regenerating
      rat liver.
AB  - Previous reports have suggested that dl-propranolol (PRL) suppresses DNA
      synthesis by blocking cAMP-mediated signaling in rat liver after partial
      hepatectomy (PH). Here, we examined if PRL negatively regulates the expression of
      genes involved in cell cycle progression. Immunoblotting assays showed that the
      protein levels of cyclins A and E, Cdk2, p21WAF1, and p27KIP1 did not
      significantly change in liver tissues from either vehicle- or PRL-injected rats
      after PH. However, the levels of PCNA and PCNA-mRNA markedly decreased in the
      remnant liver in response to PRL-injection. Similarly, PCNA-CRE binding activity
      of nuclear 43kDa CREB was suppressed, although the protein levels were not
      altered. We suggest that PRL negatively regulates the PCNA-gene transcription by
      interfering with the cAMP/PKA-mediated induction of CREB binding to the CRE
      sequences and thereby suppresses DNA synthesis in regenerating rat liver.

PMID- 9192091
TI  - Thromboxane A2 mediates cisplatin-induced apoptosis of renal tubule cells.
AB  - The purpose of this study was to elucidate the role of thromboxane A2 (TXA2) in
      cisplatin-induced apoptosis of mouse renal cells derived from the terminal
      proximal tubule (S3). RT-PCR analysis revealed that S3 cells express TXA2
      receptor mRNA. A TXA2 receptor antagonist, KW-3635, dose-dependently inhibited
      cisplatin-induced apoptosis of S3 cells. Treatment of S3 cells with a TXA2
      agonist, STA2, induced a significant decrease in their viability and resulted in
      the characteristic ladder pattern resulting from intranucleosomal DNA cleavage.
      Treatment with KW-3635 resulted in attenuation of the increase in c-fos mRNA
      expression level in cisplatin-treated S3 cells. In conclusion, TXA2 appears to
      mediate cisplatin-induced apoptosis of S3 cells by inducing an increase in the
      level of c-fos mRNA expression.

PMID- 9192092
TI  - Effect of free fatty acids on erythrocyte morphology and membrane fluidity.
AB  - Changes in red blood cell shape and membrane properties in response to the
      interaction with free fatty acids and their derivatives were studied by light
      scattering at small and large angles, light microscopy and fluorescence
      anisotropy. The influence of these agents depended on the end groups and
      increased with increasing chain length. The fatty acids exerted a biphasic effect
      on the cell size, shape and surface properties, and induced erythrocyte
      aggregation. After transient size alteration with a reduction in diameter, caused
      by low free fatty acid concentrations (up to 5-10 microM in the case of palmitic
      acid), fatty acids increased the erythrocyte diameter at higher concentrations
      (20-60 microM in the case of palmitic acid). The aliphatic aldehydes and methyl
      esters of fatty acids significantly decreased the cell diameter at the
      concentrations used. Changes in erythrocyte shape and size were accompanied by
      changes in membrane microviscosity. Palmitic acid decreased the rotational
      diffusion of the fluorescence probe incorporated into the membrane whereas methyl
      ester of palmitic acid and lauric aldehyde increased probe mobility. Also the
      erythrocyte modification by malondialdehyde influenced cell morphology and highly
      decreased membrane fluidity.

PMID- 9192093
TI  - Influence of Mycobacterium tuberculosis catalase gene (KatG) expression on nitric
      oxide production and the intracellular growth of transfected Mycobacterium
      smegmatis strains within murine macrophages.
AB  - Expression or possession of catalase gene may interfere with the iNOS/NO pathway
      in mycobacteria, hence altering their capacity to survive within macrophages.
      Therefore, strains of M. smegmatis with an inactive catalase-peroxidase gene
      (KatG), or into which the KatG gene of Mycobacterium tuberculosis had been
      transfected, were used to study the influence of catalase on nitric oxide (NO)
      production and mycobacterial survival within infected murine 1774 macrophages.
      High levels of nitrite (40-70 nM) were detected in IFN-gamma and LPS activated,
      infected murine cell culture supernatants, however, NO2- titres produced by
      infected murine cells did not differ between various catalase phenotype strains.
      Similarly, no significant difference in mycobacterial killing was also observed
      among the five strains of M. smegmatis tested over a 3 day infection period.

PMID- 9192094
TI  - Relation of biological activity of mutant forms of recombinant human tumor
      necrosis factor alpha and accumulation of sphingosine in murine liver.
AB  - TNF-alpha induced sphingomyelin hydrolysis by sphingomyelinase and both
      sphingosine and ceramide generation have been reported to be implicated in a
      number of TNF-alpha responses, including cytotoxicity and apoptosis. We found
      that sphingosine, a highly cytotoxic product of enzymatic degradation of
      sphingomyelin, is accumulated in liver of mice treated with TNF-alpha. To
      determine the role of sphingosine in TNF-alpha toxicity, TNF-alpha mutants
      differing in their cytotoxicity to L929 cells as well as haemorrhagic tumor
      necrosis, tumor regression and lethal toxicity in mice were used in our
      experiments. The mutants with highest toxicity and tumor-necrotizing activity
      caused accumulation of sphingosine exceeded its control level 5,5 times in murine
      liver cells. TNF-alpha variants which caused moderate increase in sphingosine
      content were significantly less toxic. The observed relationship between toxicity
      of TNF-alpha mutants, the toxicity of sphingosine, and the extent of its
      accumulation in murine liver provides evidence to suggest that this sphingomyelin
      metabolite may be mediator of TNF-alpha-induced cell damage and death.

PMID- 9192095
TI  - Suppression of Helicobacter pylori urease activity by sucralfate and
      sulglycotide.
AB  - The effect of gastroprotective agents, sucralfate and sulglycotide, on the in
      vitro activity of H. pylori urease was investigated. The bacterium was subjected
      to sonication, centrifuged, and the supernatant used as an enzyme source. The
      assays revealed that the rate of urea degradation was proportional to enzyme
      protein up to 100 micrograms and remained constant with time for 10 min.
      Introduction of sucralfate or sulglycotide to the assay system led to the
      reduction in the rate of ammonia production. With both drugs the optimal
      inhibition was attained at 10 micrograms/ml, at which dose a 63.1% decrease in
      urease activity occurred with sucralfate and a 70.2% inhibition was obtained with
      sulglycotide. The findings demonstrate that the inhibitory action of sucralfate
      and sulglycotide on H. pylori urease activity may be of value in the treatment of
      gastric disease associated with H. pylori infection.

PMID- 9192096
TI  - A specific assay for discriminating between peroxidase and lipoxygenase
      activities.
AB  - Peroxidases are widespread heme-containing enzymes able to catalyze the oxidation
      of a large array of organic substrates. There is growing interest in the
      measurements of peroxidase activity. We noticed that many substrates used in the
      routine assays for the biological and cytological determinations of peroxidase
      could be oxidized by lipoxygenase. We found interesting to set up a procedure to
      detect selectively peroxidase. In the present note, we report a fluorometric test
      for peroxidase detection using phenolic compounds or hydroxycoumarins.

PMID- 9192097
TI  - Simple and reliable procedure for PCR amplification of genomic DNA from yeast
      cells using short sequencing primers.
AB  - Yeast is widely used in molecular biology. Heterologous expression of recombinant
      proteins in yeast involves screening of a large number of recombinants. We
      present an easy and reliable procedure for amplifying genomic DNA from freshly
      grown cells of the methylotrophic yeast Pichia pastoris by means of PCR without
      any prior DNA purification steps. This method involves a simple boiling step of
      whole yeast cells in the presence of detergent, and subsequent amplification of
      genomic DNA using short sequencing primers in a polymerase chain reaction assay
      with a decreasing annealing temperature.

PMID- 9192098
TI  - Selective excitation of tryptophans in OmpF: a fluorescence emission study.
AB  - The fluorescence studies of E. coli porin OmpF at pH 7.5 were carried out using
      excitation at 280 and 305 nm. Similar studies were performed in presence of a
      denaturant (urea) and a quencher (KI). Results show that both the tryptophans
      present in OmpF (residue numbers 61 and 214) contribute to fluorescence at 280 nm
      excitation, whereas only one residue shows fluorescence emission when excited at
      305 nm. Based on these findings and the available crystal structure, it is
      speculated that tryptophan 61 of OmpF is selectively excited at 305 nm. The
      present studies point out some interesting features of the tryptophan
      microenvironments in OmpF.

PMID- 9192099
TI  - Further biochemical and biophysical characterisation of scyllin, Scylla serrata
      hemolymph lectin.
AB  - The amino acid and carbohydrate analysis of scyllin, a low molecular weight
      lectin purified from Scylla serrata (edible crab) haemolymph reveal that scyllin
      is rich in acidic and neutral amino acids and contains high amount of mannose. UV
      absorption of scyllin is perturbed by DMSO at 272 nm showing the presence of
      tryptophan molecule in scyllin exposed and accessible to the solvent. The
      oxidation of tryptophan molecule by N-bromosuccinimide results in loss of
      haemagglutinating activity of lectin. The study of thermodynamic parameters of
      scyllin-glycoproteins interaction suggests that ceruloplasmin is the most potent
      inhibitors of scyllin of all the glycoproteins studied.

PMID- 9192100
TI  - Ontogeny of neurotransmitter amino acids in human fetal brains.
AB  - A wide spectrum of developmental profiles is presented for a few important
      neurotransmitter amino acids, namely gamma-aminobutyric acid, glycine, glutamic
      acid, aspartic acid and taurine as well as the key enzymes involved in their
      metabolism in human fetal brains of different gestational ages. Besides taurine
      almost all these amino acids and their key metabolic enzymes were found to be
      progressively enhanced upto the mid period of third trimester of pregnancy
      indicating a rapid growth of nerve processes, myelination and maturation of fetal
      brains particularly during this period. Interestingly taurine showed an inverse
      relationship of ontogenic pattern with respect to its biosynthesizing enzyme in
      fetal brains.

PMID- 9192101
TI  - Acetylcholinesterase activity of normal and diabetic human erythrocyte membranes:
      the effect of oxidative agents.
AB  - The activity characteristics of membrane acetylcholinesterase from red blood
      cells of diabetic patients are very different from those of healthy donors: the
      limiting enzyme reaction rate is 17.2 +/- 0.8 mumol acetylthiocholine per ml
      packed cells per min compared with 13.1 +/- 0.8 mumol for control cells. This
      Michaelis constants for substrate are the same: 0.061 +/- 0.007 mM for diabetic
      and 0.061 +/- 0.004 mM for control cells. Cell exposure to oxidative agent (t
      butyl hydroperoxide) significantly changes the enzyme activity parameters. The
      limiting enzyme reaction rate increases but the affinity for the substrate
      decreases at lower oxidant concentrations (up to 0.1 mM for the "diabetic"
      erythrocytes and up to 0.4 mM for the control ones). At higher oxidant
      concentrations both the limiting reaction rate and the Michaelis constant
      decrease. The susceptibility of erythrocyte membranes of diabetic patients to
      oxidative stress is much higher in comparison with control erythrocyte membranes.

PMID- 9192102
TI  - Half-life of Escherichia coli polyadenylated lipoprotein mRNA.
AB  - In the light of recent evidence that the half-life of bacterial mRNA may be
      modulated by polyadenylation at the 3' end, we determined the half-life of
      polyadenylated lpp mRNA, which is an abundant and comparatively stable message
      encoding a major lipoprotein of the outer membrane. Messenger RNAs were pulse
      labeled with [3H] adenosine and poly(A) RNA was isolated at various times after
      pulse-labeling by affinity chromatography on oligo(dT) cellulose. The amount of
      lpp mRNA remaining was quantitated by hybridization with the antisense strand of
      the lpp gene cloned in M13mp18. The observed half-life for polyadenylated lpp
      mRNA was 12 min. This represents the first half-life measurement for a specific
      polyadenylated mRNA in E. coli, and is slightly longer than the half-life of
      total lpp RNA reported earlier. It coincides with the functional half-life for
      lpp mRNA determined by Inouye and coworkers by measuring the rate of lipoprotein
      synthesis at various times after rifampicin addition. This suggest that
      polyadenylated lpp RNA is the predominant and translationally active form of lpp
      mRNA within the cell.

PMID- 9192103
TI  - Systematic analysis of post-administrative saiboku-to urine by liquid
      chromatography to determine pharmacokinetics of traditional Chinese medicine.
AB  - To disclose the mystery of a traditional Chinese medicine and to identify
      biologically active components, we analysed post-administrative urine for Saiboku
      To, an anti-asthmatic Chinese herbal remedy. Systematic analysis of the
      components appearing in the urine was carried out by high-performance liquid
      chromatography (HPLC) with normal- and reversed-phase modes in combination. beta
      D-glucuronidase-treated urine was subjected to rapid-flow fractionation (RFF) to
      achieve fractional extraction of lipophilic components with exhaustive recovery
      rates. The extracts were analysed by HPLC equipped with a multi-channel UV
      detector. In the first stage of HPLC, we conducted a normal-phase mode run to
      find magnolol derived from Magnolia officinalis, as the most hydrophobic
      component showing minimum retention time among the urinary products of Saiboku
      To. In the next stage, mobile phase solvent composition for reversed-phase HPLC
      was optimized so as to retain magnolol up to 60 min. Under these conditions,
      other Saiboku-To urinary products, which were more polar than magnolol, appeared
      within 60 min. Our HPLC method used marker compounds like magnolol and could
      indicate the terminal peak position on the reversed-phase chromatography. We
      found a total of eight components in the post-administrative Saiboku-To urine.
      Structure identification of the isolated pure materials was achieved using
      nuclear magnetic resonance (NMR)-, mass (MS)- and UV-spectra, and HPLC retention
      profiles. They were magnolol and 8,9-dihydroxydihydromagnolol stemming from M.
      officinalis, medicarpin and liquiritigenin from Glycyrrhiza glabra, baicalein,
      wogonin, and oroxylin A from Scutellaria baicalensis, and davidigenin of an
      unknown origin. The pharmacological mystery of Saiboku-To should be disclosed by
      resolving the pharmacokinetics and pharmacodynamics of these urinary products
      independently and synergistically.

PMID- 9192104
TI  - Determination of saccharides labelled with a fluorescent reagent, DBD-ProCZ, by
      liquid chromatography.
AB  - Saccharides were determined by high-performance liquid chromatography (HPLC)
      after precolumn tagging with 4-(2-carbazoylpyrrolidin-1-yl)-7-(N,N
      dimethylaminosulphonyl )-2,1, 3-benzoxadiazole (DBD-ProCZ). The tagging
      conditions were optimized with D-glucose. Monosaccharides and oligosaccharides
      were efficiently labelled under conditions of 65 degrees C for 180 min in water:
      acetonitrile mixture containing 0.5% trichloroacetic acid (TCA). The resulting
      derivatives were detected at 540 nm (excitation at 450 nm) after separation by
      HPLC. The separation of individual saccharides was possible using water:
      acetonitrile as the mobile phase using a reversed-phase column (Inertsil ODS-80A)
      and a normal-phase column (TSKgel Amide-80). N-Acetyl-D-glucosamine (GluNAC), N
      acetyllactosamine (LacNAC) and tri-N-acetyl-chitotriose (tri-N-AceChito), which
      are components of glycoconjugates, were completely separated with an isocratic
      elution using as Inertsil ODS column. The on-column detection limit with the
      proposed HPLC separation and fluorescence detection at the low pmol level.

PMID- 9192105
TI  - 1-(5-Dimethylamino-1-naphthalenesulphonyl)-(S)-3-aminopyrrolidine (DNS-Apy) as a
      fluorescence chiral labelling reagent for carboxylic acid enantiomers.
AB  - 1-(5-Dimethylamino-1-naphthalenesulphonyl)-(S)-3-aminopyrrolidi ne (DNS-Apy) has
      been synthesized for the separation of carboxylic acid enantiomers by high
      performance liquid chromatography (HPLC) and sensitive detection. The reagent
      reacts with carboxylic acids at room temperature in the presence of activation
      agents 2,2'-dipyridyl disulphide (DPDS) and triphenylphosphine (TPP). The maximum
      emission of the diastereomeric amide derived from (S)-phenylpropionic acid and
      ketoprofen derivatives of DNS-Apy was at 530 nm with excitation at 340 nm. The
      emission wavelength shifted towards the blue and the fluorescence intensities
      increased with increasing acetonitrile concentration in the medium. The
      diastereomers derived from anti-inflammatory drugs were efficiently resolved with
      a reverse-phase column using water:acetonitrile mixture as mobile phase. All of
      the racemate of arylpropionic acid derivatives gave equal fluorescence intensity
      of the two enantiomers with the exception of ketoprofen derivatives where the
      intensity of the first eluting enantiomer was half that of the second.

PMID- 9192106
TI  - Accumulation pattern of pesticides in tropical fresh waters.
AB  - High-performance liquid chromatography has been used to study the persistence of
      commonly used organophosphorus and carbamate pesticides-carbaryl, carbendazim,
      carbofuran, dimethoate, malathion and methyl parathion in river water in the
      presence of bottom sediment in laboratory aquaria. The fate of pesticides in
      water and sediment in pre- and post-monsoon water from three sources has been
      compared. It has been established that rapid degradation occurs once the
      pesticide leaches into sediment from water. Degradation was at a much faster rate
      in post-monsoon water and sediment. It was found that pH and organic matter
      content affect rate of decay.

PMID- 9192107
TI  - A simple method for the purification of type 1 RIPs.
AB  - We describe a straightforward and simple method for obtaining pure and active
      preparations of type 1 ribosome inactivating proteins (RIPs). The very high
      isoelectric point values, characteristic of these proteins, allow this
      purification in a single chromatographic step.

PMID- 9192108
TI  - Selective and sensitive determination of protein and non-protein amino acids by
      capillary gas chromatography with nitrogen-phosphorus selective detection.
AB  - A selective and sensitive method for the determination of protein and non-protein
      amino acids by capillary gas chromatography (GC) has been developed. The amino
      acids were converted into their N(O,S)-isobutoxycarbonyl methyl ester derivatives
      and measured by GC with nitrogen-phosphorus selective detection using a DB-17ht
      capillary column. Using this method, the derivatives of the 21 protein amino
      acids and the 33 non-protein amino acids provided excellent NPD responses, and
      were quantitatively and reproducibly resolved within 28 min. The detection limits
      of these amino acids were 6-150 pg per injection. The calibration curves were
      linear in the range 0.02-2 micrograms for each amino acid, the correlation
      coefficients being above 0.990. This method was successfully applied to small
      urine samples without prior clean-up, and analysed without any influence from
      coexisting substances. Overall recoveries of amino acids added to urine sample
      were 83-108%. The analytical results of free amino acid contents in urine samples
      of normal subjects are presented.

PMID- 9192109
TI  - TLC characterization of liposomes containing angiotensinogen, angiotensine I,
      angiotensine II and saralazin.
AB  - Recent studies have described intracellular binding sites for angiotensine II. In
      vascular smooth muscle it was found that intracellular injection of angiotensin
      II increases the Ca2+ level. An alternative method for intracellular delivery of
      drugs is represented by using liposomes. Thus, the aim of this study was to
      characterize liposomes filled with angiotensinogen, angiotensine I (Ang I),
      angiotensine II (Ang II), and saralasin by a TLC method and examine the
      physiological effects of these on rat vascular smooth muscle. Ang II (for all
      concentrations tested in the aqueous phase) and Ang I (for concentrations less
      than 10(-4)M) did not affect the thin-layer chromatography migration of this type
      of vesicle, suggesting that dose-dependent effects on physio-pharmacological
      experiments could be studied. On the other hand, this type of experiment could
      not be performed for salarasin- or angiotensinogen-filled liposomes.
      Administration of liposomes containing Ang II (10(-6)M), Ang I (10(-6)M),
      angiotensinogen (10(-6)M) and saralasine (10(-6)M) caused the contraction to
      isolated rat aorta smooth muscle, suggesting the presence of active intracellular
      binding sites.

PMID- 9192110
TI  - Removal of endotoxin from aqueous solutions by affinity membrane.
AB  - Endotoxin was removed by affinity membranes with histidine immobilized as
      affinity ligand. Macropore cellulose membrane was prepared from filter paper by
      alkaline treatment and chemical crosslinking, and was used as matrix for the
      immobilization of affinity ligand. The matrix membrane was derived by
      hexamethylenediamine and activated by glutaraldehyde before histidine was
      immobilized. Membrane cartridges containing 40 or 80 sheets of affinity membrane
      were also prepared, which can be used to remove pyrogen from aqueous solutions.
      Using a cartridge with 40 sheets of affinity membrane, the endotoxin content in
      solution can be reduced to a minimum of 0.12 EU/mL.

PMID- 9192111
TI  - Cyclohexylamine additives for enhanced peptide separations in reversed phase
      liquid chromatography.
AB  - While the choice of stationary phase, organic modifier, and gradient strength can
      have significant effects on biomolecule separations, mobile phase additives can
      also have a significant effect on the chromatographic selectivity, recovery,
      efficiency and resolution. Given the importance of stationary phase coverage, the
      beneficial, silanol-masking properties of amines, and the potential for
      selectivity modification through ion-pair interactions, cyclohexylamine was
      examined as a mobile phase additive and compared with triethylamine and
      trifluoroacetic acid. Greatly improved separation was possible when
      cyclohexylamine was used as compared with phosphate buffer, and cyclohexylamine
      did not require purification before use, while triethylamine required
      distillation before 'clean' chromatograms were obtained.

PMID- 9192112
TI  - Insertion of MAP4-VP1 peptide into lipid monolayers and bilayers.
AB  - Myscibility of dipalmitoylphosphatidylcholine (DPPC) with
      dipalmitoylphosphatidylglycerol (DPPG), cardiolipine (CL) and
      dipalmitoylphosphatidylethanolamine (DPPE) was studied using monomolacular layers
      of different compositions. The influence of MAP4-VP1 peptide construct related to
      HAV protein in mixed monolayers of the above cited lipid components was
      determined following penetration kinetics and compression isotherms. Moreover,
      liposomes with the same composition as monolayers were saturated with ANS or DPH
      and incubated with MAP4VP1, and polarization values as well as transition
      temperatures were determined. In general interaction is maximum with DPPC/DPPG
      mono and bilayers, followed by DPPC/CL. In these systems electrostatic repulsive
      forces seem to play a strong role.

PMID- 9192113
TI  - Enantiomeric determination of the phenylmorpholinol metabolite of bupropion in
      human plasma using coupled achiral-chiral liquid chromatography.
AB  - A coupled achiral-chiral stationary phase liquid chromatographic technique was
      developed to separate and quantitate the enantiomers of the phenylmorpholinol
      metabolite (2) of the antidepressant bupropion (1) in human plasma. At the
      retention time of 2, a switching valve loaded a portion of the eluting compound
      onto a protein-bonded chiral stationary phase which resolved 2 into the (+) and (
      ) stereoisomers using an aqueous mobile phase of potassium phosphate (pH = 6.25)
      and 5% 2-propanol. All eluting compounds were monitored using UV detection at 214
      nm, and no plasma endogenous material or other commonly used psychotropic drugs
      were found to interfere. Within-day and between-day variation were less than 6%
      over the expected concentration range, and a limit of quantitation of about 125
      ng/mL of 2 was observed. Steady-state plasma samples from 17 patients receiving 1
      were found to contain the (-) enantiomer to the extent of about 96% of total 2.
      The potential clinical implications of these results are not known since all
      previous pharmacological studies were carried out with the racemic 2.

PMID- 9192115
TI  - Family doctors: players or spectators in the future?

PMID- 9192116
TI  - Beta adrenergic blocking drugs and the Borg rating scale of perceived exertion.

PMID- 9192114
TI  - Affinity chromatography of yeast alcohol dehydrogenase using immobilized
      monochlorotriazine colourless compounds.
AB  - Four new symmetrical colourless biomimetics bearing two monochlorotriazine rings
      have been rationally designed and synthesized. These immobilized colourless
      ligands and one analogue of Cibacron Blue F3GA on Sepharose CL-4B were used to
      purify alcohol dehydrogenase from baker's yeast extract. Twenty-two-fold
      purification with 78% enzyme recovery was achieved in a single step with specific
      elution of NAD+ (5 mM) from the colourless absorbent comprised of two ortho
      aminobenzene sulphonates as terminal rings, which is comparable to the result
      obtained from the analogue of Cibacron Blue F3GA. Differential spectra between
      ligand-enzyme complexes and free ligands were studied.

PMID- 9192117
TI  - Gymnastics: changing for the better?

PMID- 9192118
TI  - Rugby, injury, and the lions.

PMID- 9192119
TI  - Sports injury clinics.

PMID- 9192120
TI  - Management of groin pain in athletes.
AB  - Groin pain is a difficult clinical problem because of the variety of conditions
      that are potentially responsible. Much of the "theory" of groin pain is just
      that, theory, and much needs to be done to document the pathomechanics and
      symptomatology of this anatomical region. Notwithstanding the above, clinicians
      should be comfortable in the knowledge that they can provide relief in most cases
      and a cure in more than a few. The recommended diagnostic approach is anatomical,
      supported by judicious selection of diagnostic imaging techniques. Management
      then comprises a considered approach to functional recovery, allowing time to
      heal, regain strength, and restore mobility. Patients should be reminded that
      there are no short cuts and precipitate return to sport is not worth the risk in
      most cases.

PMID- 9192121
TI  - Role of ankle taping and bracing in the athlete.
AB  - Adhesive tape is often used to help athletes recover from ligament sprains of the
      ankle or to prevent further injury. The choice of taping technique or material is
      often decided by personal preference, superstition, or anecdote. More recently,
      the use of ankle braces has become more prevalent, but reasons for their use are
      similarly variable. As ankle sprains are a major cause of an athlete's disability
      and time off sport, the choice of the method of support should be more
      scientifically reasoned. This paper attempts to review the literature concerning
      the effects of various methods of ankle support on swelling, stability, range of
      movement, proprioception, muscle function, gait, and performance tests. There is
      still some contradiction in the literature about the effects of taping and braces
      in both the acute and chronic phases of ligament sprains of the ankle.

PMID- 9192122
TI  - An investigation into the relation between step height and ground reaction forces
      in step exercise: a pilot study.
AB  - The aim of this study was to investigate the effect that changing step height had
      on ground reaction force. Using a randomised crossover design, 12 volunteers with
      no previous experience of step aerobics were recruited to perform at three
      different step heights: 6, 8 and 10 inches. Subjects performed a basic step at a
      cadence of 120 beats/min and performed three one minute trials during which
      ground reaction force was measured. Measurement of peak impact force, time to
      achieve peak impact, and total time of foot contact was made, and impulse of the
      force was calculated. Statistically significant differences were found to exist
      for peak impact force between the 6 and 8 inch and 6 and 10 inch, but not between
      the 8 and 10 inch conditions. No significant differences were found in any other
      parameters. The study supports the present advice that participants should use
      low step heights, and possible mechanisms of injury are discussed.

PMID- 9192123
TI  - Use of ratings of perceived exertion for predicting maximal work rate and
      prescribing exercise intensity in patients taking atenolol.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of Borg's rating
      of perceived exertion (RPE) scale to predict maximal exercise levels to control
      exercise intensity in patients taking atenolol for the treatment of essential
      hypertension. Normally, a standard formula (220-age) is used for calculating a
      percentage of exercise intensity, but beta blockade can cause reductions in
      maximal heart rate of between 20 and 30%. METHODS: Patients were split into a
      control group-10 men and 10 women, aged 50 (SD 12) and 46 (9) respectively, who
      had risk factors for cardiovascular disease but were not taking any drugs, and a
      treatment group-11 men and 11 women, aged 53 (13) and 55 (13) respectively, who
      were established on 25-100 mg of atenolol. All patients performed two submaximal
      tests on a cycle ergometer. Test 1 was an estimation test, during which the RPE
      was reported for each increment in work rate. Test 2 was an RPE production test,
      during which the patient regulated the work rate according to his/her perception
      of effort at four predetermined points on the RPE scale (RPE 9, 13, 15, 17).
      RESULTS: In both tests the individual correlations (r) between RPE, heart rate,
      and work rate ranged from 0.96 to 0.99. Analysis of variance showed no
      significant difference in maximal heart rate and maximal power output for the
      control group when predicted from the regression lines of RPE versus heart rate
      and RPE versus power output in the estimation test. However, the prediction of
      maximal power output was lower in the women in the control group and patients in
      the treatment group when this was predicted from the effort production protocol
      (P < 0.01). When exercise intensity at each RPE was expressed relative to maximal
      power output there were no differences between treatment and control groups.
      CONCLUSION: The findings from this study confirmed the strong positive relation
      between RPE, heart rate, and work rate in these patients in both passive effort
      estimation and active effort production protocols. However, caution in applying
      these procedures is required because the prediction of maximal exercise levels
      may be lower when effort production procedures are used.

PMID- 9192124
TI  - Exercise metabolism in healthy volunteers taking celiprolol, atenolol, and
      placebo.
AB  - OBJECTIVE: Previous studies have shown that beta 1 selective agents have fewer
      adverse effects on exercise metabolism than nonselective beta blockers, and this
      has been attributed to their reduced blockade of beta 2 receptors. This study
      aimed at determining whether a beta blocker with partial agonist activity at beta
      1 and beta 2 receptors (celiprolol) was better than a conventional beta 1
      receptor-blocker (atenolol) in prolonging exercise capabilities. METHODS: After
      four days of treatment with celiprolol 200 mg, atenolol 50 mg, or placebo, 22
      healthy volunteers exercised on a treadmill for two hours at 50% of their maximal
      oxygen uptake. Resting heart rate and blood pressure were recorded before and
      after exercise. During exercise, fat oxidation, plasma free fatty acids,
      glycerol, glucose, and ammonia were measured together with heart rate and
      perceived exertion. RESULTS: Mean exercising heart rate was significantly lower
      in those taking either of the beta blockers than in those taking placebo, and
      significantly lower for those taking atenolol rather than celiprolol. Fat
      oxidation was significantly lower for those taking celiprolol (38.8 (SD 12.2)%, P
      < 0.01) and atenolol (36.6 (15.9)%, P < 0.01) compared with placebo (45.6
      (14.1)%). For the first 15 minutes of exercise, fat oxidation was significantly
      lower for those taking atenolol (24.6 (12.8)%, P < 0.01) than celiprolol (29.6
      (14.3)%). The rise in plasma free fatty acids and glycerol during exercise was
      also significantly attenuated by both beta blockers in comparison with the rise
      in those taking placebo (P < 0.01). CONCLUSIONS: Both celiprolol and atenolol
      reduced fat oxidation compared with placebo. For the first 15 minutes of exercise
      fat oxidation was preserved by celiprolol, but not atenolol. This preservation of
      fat oxidation during the early part of exercise may confer some small benefit to
      patients who take beta blockers and intend to exercise regularly. However, we did
      not detect significant differences between atenolol and celiprolol in overall
      mean fat oxidation or perceived exertion in this study.

PMID- 9192125
TI  - Drug doping in senior Australian rules football: a survey for frequency.
AB  - OBJECTIVES: To determine by survey whether the frequency of use of performance
      enhancing drugs (drug doping) is significant in elite players of Australian Rules
      football, and to compare this frequency with that in other competitions. METHODS:
      Randomised unannounced prospective urine testing during the period 1990-95 of
      players from the Australian Football League out of competition, in competition
      matches, and in finals matches; testing was performed according to Olympic
      International Committee protocols and standards. The players' identities and
      clubs were unknown during testing. RESULTS: Of 900 random urine tests, no
      positive results were obtained for anabolic steroids, diuretics, caffeine, or
      peptide hormones. Five positive results (0.6%) were obtained-for pseudoephedrine
      in two instances, and for probenecid, methoxyphenamine, and dextropropoxyphene in
      one instance each. Each were inadvertent medical doping and declared before
      testing. CONCLUSIONS: Drug doping is not a problem in the Australian Football
      League. This is probably because no doping method is considered to be of value to
      Australian Rules football, because an educational programme is run by football
      authorities, and because random during season and out of season testing for drugs
      occurs.

PMID- 9192126
TI  - General practitioner knowledge of prohibited substances in sport.
AB  - OBJECTIVES: To assess general practitioner knowledge of banned substances in
      sport. METHODS: Postal questionnaire sent to all general practitioners in West
      Sussex. RESULTS: Only 55 (35%) of those who responded (157 in total) were aware
      that guidelines are to be found in the British National Formulary, and 19 (12%)
      of respondents believed that medical practitioners are allowed to prescribe
      anabolic steroids for non-medical reasons. CONCLUSIONS: General practitioner
      knowledge of which substances are prohibited in sports is poor. There is a lack
      of awareness of Sports Council guidelines which are to be found in the British
      National Formulary. Tackling drug abuse in sport requires education of both
      athletes and doctors.

PMID- 9192127
TI  - Injury consequences from participation in professional rugby league: a
      preliminary investigation.
AB  - OBJECTIVE: To conduct a preliminary investigation to determine if injuries
      sustained while playing professional rugby league have long term consequences for
      players after retirement from their playing careers. METHOD: Twenty eight retired
      players, who had competed in the professional Australian Rugby League
      competition, responded to a 23 item survey. Respondents were asked to recall all
      injuries that resulted in them being unable to play for five or more consecutive
      games. The survey asked players to provide information about age, playing weight,
      number of games played, position played, number and type of major injuries
      sustained during their career, and the effects of these injuries both during
      their career and after retirement. RESULTS: Within the limitations of this
      study's small sample, it is suggested that players with long term consequences of
      injury may experience a variety of detrimental effects into retirement, including
      job limitations, reduced income earning potential, and increased personal medical
      costs. CONCLUSION: Although research relating to the type and severity of
      injuries sustained while playing rugby league has been previously undertaken,
      investigation into the effect injuries sustained during a professional career
      have on players after retirement has been neglected. This preliminary
      investigation suggests that retired professional rugby league players may have at
      least one long term consequence of injuries sustained during their playing
      career.

PMID- 9192128
TI  - Influence of players' physique on rugby football injuries.
AB  - OBJECTIVES: To determine whether there is an association between a player's
      physique and injuries incurred while playing rugby football. METHODS: A cohort
      study was carried out involving all senior rugby clubs in the Scottish Borders
      during the 1993-1994 rugby season. Somatotype estimates were determined for 1152
      (95%) of the 1216 eligible players. Body mass index (BMI), chest to waist ratio,
      and the ponderal index (PI) were used to classify players' physique as
      endomorphic (obese), mesomorphic (muscular), and ectomorphic (linear). RESULTS: A
      strong association was found between physique and age (chi 2 test: chi 2 = 317.2,
      df = 10, P < 0.0001). More younger players were ectomorphs. Older players were
      more often endomorphic. The physiques of forwards and backs were significantly
      different (chi 2 test: chi 2 = 58.6, df = 2, P < 0.0001), with forwards being of
      a heavier build than three-quarters, even after adjustment for age. Endomorphic
      players were more likely than ectomorphs to be injured in a match after
      adjustment for age (age-adjusted mean BMI for players who were injured in a match
      was 25.4 compared with 24.6 for players who were not injured in a match, P <
      0.0001; adjusted chest to waist ratio means were 1.136 and 1.125 respectively, P
      = 0.0307; adjusted PI means were 0.414 and 0.417 respectively, P = 0.0056).
      Increased risk of injury may occur when players play out of position, since one
      fifth of all injuries occurred in this circumstance. CONCLUSIONS: Further
      research needs to be conducted using a more objective method of measuring
      somatotype on a further cohort of players so that the risk of injury for
      different body types can be examined more closely and related to other potential
      confounding factors. The level of increased risk for individuals playing out of
      their usual playing position needs to be established with a greater degree of
      certainty.

PMID- 9192129
TI  - Responses of young girls to two modes of aerobic training.
AB  - OBJECTIVES: To investigate the physiological effects of two different three times
      a week, eight week training programmes on the aerobic fitness of nine to ten year
      old girls. METHODS: Treadmill determined peak VO2, submaximal heart rates, and
      submaximal blood lactate were the criterion measures. Seventeen girls completed a
      programme of "aerobics" training where sessions lasted 20-25 minutes. Eighteen
      girls followed a cycle ergometer training programme which involved pedalling
      continuously for 20 minutes with the heart rate maintained between 160 and 170
      beats/minute. A control group of 16 girls completed the criterion tests but did
      not train. In the cycle ergometer group and eight control subjects plasma total
      cholesterol and high density lipoprotein cholesterol were determined before and
      after training. RESULTS: Peak VO2 did not change significantly with training in
      either training group, neither were there any significant changes in submaximal
      heart rates. Blood lactate declined significantly at the two lowest submaximal
      exercise intensities in the cycle ergometer training group (from 2.3 (1.1) to 1.4
      (0.06) mmol/l at stage 1 and from 2.1 (1.2) to 1.6 (0.06) mmol/l at stage 2;
      means (SD); P < 0.01). Total cholesterol and high density lipoprotein cholesterol
      remained unchanged with training. CONCLUSIONS: These findings suggest that an
      eight week structured exercise programme produces minimal changes in either the
      aerobic fitness or blood lipids of young girls. It may be more beneficial for
      long term health to promote enjoyment in activity and positive attitudes to
      exercise rather than attempting to enhance aerobic fitness through strenuous
      exercise programmes.

PMID- 9192130
TI  - Bone mineral density in professional female dancers.
AB  - OBJECTIVES: To measure the long term effects of dance training and the
      contribution of the timing and duration of any menstrual disruption on bone
      mineral density (BMD). DESIGN: Measurement of BMD in 57 premenopausal, previously
      professionally dance trained women and the relationship to menstrual and training
      history. MAIN OUTCOME MEASURES: Bone density measurements at lumbar spine and
      femoral neck by dual energy x-ray absorptiometry. RESULTS: The average Z score
      for BMD at the lumbar spine in the amenorrhoeic dancers was significantly below
      that for the normal population. The average Z score for BMD at the femoral neck
      in the eumenorrhoeic dancers was significantly above that for the normal
      population. There was a significant difference between the average Z score for
      BMD at both the lumbar spine and femoral neck between the amenorrhoeic and
      eumenorrhoeic dancers. Significant negative relationships were found between BMD
      at the lumbar spine and (1) age at menarche, (2) duration of amenorrhoea, (3) BMD
      at the femoral neck, and (4) the variable of ideal minus lowest weight, which was
      independent of amenorrhoea. No significant relationships were found between
      duration of oral contraceptive pill usage and BMD at either the lumbar spine or
      the femoral neck in eumenorrhoeic or amenorrhoeic dancers. In order to quantify
      the effect of a combination of these significant factors, a model of BMD was
      constructed using multiple regression incorporating the variables duration of
      amenorrhoea, age at menarche, and ideal minus lowest body weight. In this model
      R2 was 33.6%, in other words 33.6% of the total variation in the Z score for BMD
      at the lumbar spine could be accounted for by these factors. CONCLUSION:
      Professional female dancers with a history of delayed menarche and amenorrhoea
      have been identified as another group of premenopausal women potentially at risk
      of developing osteoporosis because of a decrease in BMD at the lumbar spine. The
      femoral neck in dancers with a history of amenorrhoea was partially protected
      from loss of BMD by virtue of being the major weight bearing site in previous
      dance training, and in eumenorrhoeic dancers BMD was significantly increased at
      this site.

PMID- 9192131
TI  - Developing a health surveillance strategy for professional footballers in
      compliance with UK health and safety legislation.
AB  - The need for health surveillance for professional footballers has been assessed
      against criteria specified in UK health and safety legislation. As footballers
      suffer from chronic injuries under normal playing conditions, professional
      football clubs have a requirement to implement health surveillance programmes to
      protect their players. A health surveillance programme, based on benchmarking a
      player's fitness and addressing the issues of pre-recruitment, pre-season, during
      season, post-season, and rehabilitation assessment, is proposed.

PMID- 9192132
TI  - Moderate altitude has no effect on choice reaction time in international rugby
      players.
AB  - There are only a few conflicting reports on the effects of moderate altitude on
      cognitive factors that could affect sporting performance. An investigation of
      choice reaction time in international rugby players at various altitudes was
      therefore carried out. The results suggest that moderate altitude has no
      significant effect on this parameter in highly trained competitive athletes.

PMID- 9192134
TI  - Traumatic occlusion of the external iliac artery in a racing cyclist: a cause of
      ill defined leg pain.
AB  - Stenosis of the external iliac artery in healthy athletes, although uncommon, has
      been reported in competition cyclists. A case of a racing cyclist whose chronic
      vague leg symptoms were incorrectly attributed to L4/5 nerve root irritation is
      reported. This highlights the importance of clinical vascular testing when
      assessing ill defined leg pain. The role of trauma as a causative factor in this
      condition has not been previously documented.

PMID- 9192133
TI  - Recovery from infectious mononucleosis after altitude training in an elite middle
      distance runner.
AB  - OBJECTIVES: This investigation was designed to monitor altitude acclimatisation
      in an elite cohort of distance runners and follow the subsequent recovery from
      infectious mononucleosis which developed in one of these athletes. METHODS:
      Twenty six national standard distance runners performed treadmill tests 24 days
      before they travelled to an altitude camp (1500 to 2000 m). One of these athletes
      was diagnosed as suffering from infectious mononucleosis 14 days after return to
      sea level. A physician prescribed an individualised training programme which was
      designed to maximise recovery from the condition, which was monitored on days 16
      and 147 after altitude training. RESULTS AND CONCLUSIONS: The data suggest that
      the athlete was in a state of over-reaching during the altitude sojourn. After
      return to sea level, the early stages of infectious mononucleosis resulted in a
      marked impairment in physiological response to endurance exercise, which improved
      over time. Longitudinal physiological monitoring in conjunction with a carefully
      prescribed training programme made recovery from this condition possible.

PMID- 9192135
TI  - Dynamic obstruction of the external iliac artery in endurance athletes and its
      relationship to endothelial function: the case of a long distance runner.
AB  - There have been recent reports of exercise induced claudication in endurance
      trained athletes attributed to narrowing of the external iliac artery. Most
      patients have been competitive cyclists, and intimal hyperplasia has been cited
      as the cause. The case is reported here of a long distance runner who presented
      with similar symptoms.

PMID- 9192136
TI  - Assessing physiological responses to training in young children.

PMID- 9192137
TI  - Sternal fracture in a female army officer cadet.

PMID- 9192138
TI  - Exercise induced leg pain.

PMID- 9192139
TI  - Turf-toe: super league toe.

PMID- 9192140
TI  - Long-term psychological adjustment to witnessing interparental physical conflict
      during childhood.
AB  - A retrospective survey of undergraduate students was used to examine the long
      term psychological impact of witnessing interparental physical aggression during
      childhood. Two hundred and three of 1,452 young adults surveyed (14%) reported
      witnessing as children at least one incident of physical aggression between their
      parents. Both men and women who witnessed interparental physical conflict
      reported higher levels of current psychological distress than a comparison group
      of young adults who never observed physical aggression between their parents.
      This group difference remained even after controlling for parental divorce,
      parental SES, physical abuse of the child, parental alcoholism, and nonphysical
      discord witnessed between parents. Additional analyses found that the negative
      effect of witnessing interparental aggression was intensified when the aggression
      was serious enough to warrant some type of outside assistance for the victim and
      when the parent of the same-sex was seen being victimized. Although these
      findings provided support for the theory that witnessing interparental physical
      aggression is a traumatic experience that may have long-term psychological
      ramifications, we also found that a substantial proportion of the variance
      accounted for in adult adjustment by interparental physical conflict was mediated
      through decreased parental caring and warmth during childhood. Implications for
      these results, limitations of the present study, and directions for further
      research are discussed.

PMID- 9192141
TI  - Families of homeless and runaway adolescents: a comparison of parent/caretaker
      and adolescent perspectives on parenting, family violence, and adolescent
      conduct.
AB  - OBJECTIVE: Almost all of what is known about the families of runaways and
      homeless adolescents is based on adolescent self-reports. The validity of such
      research is currently being questioned by policy makers. The purpose of this
      study was to compare runaway and homeless adolescent reports and parent/caretaker
      reports on measures of parenting, family violence, and adolescent conduct.
      METHOD: Reports of 120 runaway adolescents and their parents/caretakers from four
      Midwestern states were compared on measures of parental monitoring, parental
      warmth and supportiveness, parental rejection, physical and sexual abuse, and
      adolescent conduct. Comparison groups of nonrunaway adolescents and their mothers
      in two-parent and single-parent families from the same geographical area were
      also used for parenting and adolescent conduct measures. RESULTS: The findings
      indicated that although there were significant differences in means between
      adults and adolescents regardless of runaway status, adults and adolescent
      reports were in the same direction and present similar portraits of families of
      runaway and homeless young people. Both the parents/caretakers and their runaway
      adolescents reported lower levels of parental monitoring and warmth and
      supportiveness and higher levels of parental rejection than comparison groups of
      nonrunaway families. Parents/caretakers and runaway adolescents reported high
      levels of family violence and sexual abuse. Similarly, they concur regarding
      conduct problems for the adolescents. CONCLUSIONS: The findings suggest that
      runaway and homeless adolescents accurately depict the troubled family situations
      that they choose to leave. The policy implications for recent debates involving
      criminalization and mandatory return to parental custody of homeless and runaway
      youth are discussed.

PMID- 9192143
TI  - Effects of ritual abuse: the results of three surveys in The Netherlands.
AB  - OBJECTIVE: We decided to document the behavior of 87 children involved in
      multiple victim/multiple perpetrator sexual abuse by developing and administering
      surveys to families. Data gathered at 2 1/2 years (1990) and 7 years (1994) after
      the disclosures indicated the behavioral status of the children at different
      developmental stages. This data was compared to clinical information available
      prior to the abuse, and initial survey data rendered at 6 weeks after disclosure
      (Jonker & Jonker-Bakker, 1991). The objective was to document the behavior of the
      victims during the healing process. METHODOLOGY: A questionnaire was sent to the
      parents of 87 children who were abused in 1987. The parents returned the
      completed questionnaire, and were interviewed in our clinic. RESULTS: Data from
      the 1990 and 1994 surveys indicate that 39% of the children involved, who lived
      in supportive family environments, had changed as a result of the abuse. They
      exhibited behavior within acceptable, normal guidelines for childhood
      development. In 1994, 7% of the children involved showed signs of more severe
      behavioral disorders. CONCLUSIONS: The findings indicate that physical and
      behavioral signs apparent in the 1990 and 1994 surveys were not recognized at the
      time the abuse occurred. Many of the children exhibit normal, acceptable behavior
      at the time of the most recent survey (1994).

PMID- 9192142
TI  - Multiple substance use among adolescent physical and sexual abuse victims.
AB  - OBJECTIVE: This study was conducted to examine the relationship between substance
      use patterns among adolescents and their histories of physical and/or sexual
      abuse. METHOD: The Minnesota Student Survey was administered in 1995 to 122,824
      public school students in Grades 6, 9, and 12. Substance user groups were created
      based on frequency of use and the number of substances used. Use of individual
      substances, use of multiple substances, age of first use, and reasons for use
      were examined with respect to histories of physical and/or sexual abuse. RESULTS:
      Physical and sexual abuse were associated with an increased likelihood of the use
      of alcohol, marijuana, and almost all other drugs for both males and females in
      the three grades surveyed. Use of multiple substances was highly elevated among
      victims of abuse, with the highest rates seen among students who reported both
      physical and sexual abuse. Abuse victims also reported initiating substance use
      earlier than their nonabused peers and gave more reasons for using, including use
      to cope with painful emotions and to escape from problems. CONCLUSION: Because of
      their increased vulnerability, young victims of physical and sexual abuse need
      improved prevention, early intervention, and treatment services related to
      substance use.

PMID- 9192144
TI  - On the threshold of disclosure. The effects of a mass media field experiment.
AB  - OBJECTIVE: To assess whether the number of disclosures of child abuse changed as
      a result of a prevention strategy on a national scale in a West-European country.
      The child abuse involved child sexual and physical abuse, both ongoing and past.
      METHODS: In order to assess possible intervention effects, changes in calling the
      Child Line were measured. For this, a 4 year longitudinal design, starting before
      the intervention and ending 2 and 1/2 years after it was used (N = 3,117
      disclosures). In addition, data were collected from the Dutch Telecom and a
      newely developed Child Abuse Form (N = 1,227). Finally, two measures were
      introduced, the disclosure coefficient and the relative disclosure coefficient.
      RESULTS: Most calls were silent calls, a phenomenon that deserves more attention
      in disclosure research. Compared to pre-intervention data, the amount of
      disclosures almost tripled during the intervention and was even further enhanced
      in the post-intervention and follow-up. In nine out of 10 cases, ongoing abuse
      was disclosed. Marked differences between child physical abuse and child sexual
      abuse were observed. CONCLUSION: It is concluded that mass media communication,
      if well implemented, can positively influence the process of disclosure of
      ongoing child abuse.

PMID- 9192145
TI  - What determines post-traumatic stress disorder symptomatology for survivors of
      childhood sexual abuse?
AB  - OBJECTIVE: The aim of this paper was to ascertain which childhood abuse
      experiences are associated with post-traumatic stress disorder (PTSD)
      symptomatology for women survivors of childhood sexual abuse (CSA). METHOD:
      Seventy-three women attending a Family Health Counselling Service's Sexual Abuse
      Program were invited to participate in a study looking at the effectiveness of
      sexual abuse counselling. Initially, the women completed a series of self-report
      questionnaires including a measure of PTSD symptoms, and were interviewed about
      childhood abuse experiences. RESULTS: PTSD symptoms were associated with higher
      levels of all psychopathology. However, more interestingly, the severity of PTSD
      symptoms was also associated with the extent of CSA which involved actual sexual
      intercourse. This association of repeated abuse involving sexual intercourse with
      PTSD symptoms was still significant (partial coefficient = .30, p, .000) even
      when controlling for general level of psychopathology. CONCLUSIONS: One of the
      long-term effects of child sexual abuse (CSA) is post-traumatic stress disorder
      (PTSD), and the women who reported multiple abusive episodes which involved
      sexual intercourse had increased symptoms of PTSD.

PMID- 9192147
TI  - Clinical correlates of changes in self-perceived oral health in older adults.
AB  - Although numerous investigators have reported on self-perceived oral health
      status in adult and older adult populations, few have examined how these
      perceptions change over time. This paper uses data from a longitudinal oral
      health survey of community-dwelling Canadians aged 50 years and over to explore
      this issue. Data were collected at baseline and after 3 years. Change was
      assessed using a global transition judgement and change scores on four subjective
      oral health status indicators. These indicators addressed chewing capacity, oral
      and facial pain symptoms, other oral symptoms, and the psychosocial impact of
      oral disorders. Overall, 23.0% reported that their oral health had worsened over
      this period, 66.5% that it had remained the same and 10.5% that it had improved.
      Change scores on the four indicators showed a similar pattern and were
      significantly associated with these global judgements. Over the same period,
      substantial proportions lost one or more teeth, acquired new coronal or root DFS
      increments or experienced loss of periodontal attachment. An additional 17%
      complained of dry mouth. However, the only clinical indicator associated with
      changing perceptions of oral health was tooth loss. Of interest was the fact that
      rates of tooth loss were equally high among those who reported a worsening of
      oral health and those who reported an improvement. This suggests that the impact
      of tooth loss on health status may be positive or negative depending upon the
      condition of the teeth lost.

PMID- 9192146
TI  - Association between carriage of oral yeasts, malnutrition and HIV-1 infection
      among Tanzanian children aged 18 months to 5 years.
AB  - The objective was to determine whether there is an association between carriage
      of oral yeasts, malnutrition and HIV-1 infection among Tanzanian children. A case
      control study design within a cross-sectional study was used, and the outcome was
      carriage of oral yeasts. The exposure variables were malnutrition and HIV-1
      antibody, and confounders to be adjusted for were age, sex, and breastfeeding.
      The study was carried out in Dar-es-Salaam, Tanzania, in two maternal and child
      health (MCH) clinics that offer routine medical checkups to all expectant mothers
      and children aged between 0 and 5 years in the catchment area. A total of 882
      children aged between 18 months and 5 years participated. Smears from the tongue
      and buccal mucosa were examined for oral yeasts. Malnutrition was categorized
      according to standards on the MCH chart and World Health Organization/Centers for
      Disease Control (WHO/CDC) standards as weight-for-height (wasted), weight-for-age
      (underweight), and height-for-age (stunted). HIV-1 infection was determined by an
      enzyme-linked immunosorbent assay. Reactive sera were confirmed by Western Blot.
      About 27% of the children were slightly or severely malnourished according to
      standards on the MCH chart. According to WHO/CDC standards, 2.6% were wasted,
      16.3% were underweight, and 29.6% were stunted. Fourteen (1.6%) were seropositive
      for HIV-1 antibody. Hyphal forms and blastospores were much more frequent among
      children infected with HIV-1 with odds ratios ranging from 3.8 (95% CI: 1.3;11.2)
      to 6.2 (95% CI: 2.1;18.4) depending on categorization of malnutrition.
      Malnutrition was a risk factor, too, albeit to a much lesser and insignificant
      degree. The study supports our previous findings that malnutrition may predispose
      to carriage of oral yeasts and subsequent infection. However, in this study
      population HIV infection was clearly the predominant risk factor.

PMID- 9192149
TI  - Prevalence of perceived symptoms of dry mouth in an adult Swedish population-
      relation to age, sex and pharmacotherapy.
AB  - The aim of the study was to evaluate the prevalence of subjective perception of
      dry mouth in an adult population and to determine the prevalence of
      pharmacotherapy in this population. An additional aim was to assess a possible co
      morbidity between symptoms of dry mouth and continuing pharmacotherapy. Four
      thousand-two-hundred persons were selected at random from the national census
      register of the adult population of the southern part of the province of Halland,
      Sweden. The sample was stratified according to age and sex, and 300 men and an
      equal number of women aged 20, 30, 40, 50, 60, 70 and 80, were included. A newly
      developed questionnaire was mailed to each individual. In addition to questions
      about subjective perception of dry mouth, the subjects were asked to report on
      present diseases and continuing pharmacotherapy. Three-thousand-three-hundred and
      thirteen (80.5%) evaluable questionnaires were returned. The estimated prevalence
      of xerostomia in the population was 21.3% and 27.3% for men and women,
      respectively. This difference between the sexes was statistically significant. In
      non-medicated subjects, women tended to report a higher prevalence of xerostomia
      compared with men, 18.8% vs. 14.6%, and also among medicated subjects the
      estimated prevalence of dry mouth was higher for women than for men, 32.5% vs.
      28.4%. There was a strong association between xerostomia and increasing age and
      also between xerostomia and continuing pharmacotherapy. The average prevalence of
      dry mouth among medicated and non-medicated subjects was 32.1% and 16.9%,
      respectively, the difference being statistically significant. There was also a
      strong association between xerostomia and the number of medications. In a
      logistic regression, the probability of reporting mouth dryness was significantly
      greater in older subjects and in women, and the probability increased with the
      number of medications taken. In conclusion, this epidemiological survey of an
      adult population has demonstrated that women, independent of age, do report a
      higher prevalence of xerostomia than men and that the symptom of dry mouth is
      strongly associated with age and pharmacotherapy. It is, however, not possible to
      discriminate between disease and pharmacotherapy as causal factors.

PMID- 9192148
TI  - Predictors of tooth loss over 10 years in adult and elderly Chinese.
AB  - This study describes the incidence of tooth loss over a 10-year period in a
      population of rural Chinese, initially aged between 20 and 80 years. Among the
      587 persons who participated in a baseline examination in 1984, 440 persons were
      available for a follow-up study in 1994. A total of 31 persons, mainly aged 50+
      years at baseline, had become completely edentulous. Between 45% and 96% of the
      persons lost at least one tooth, and the average number of teeth lost ranged
      between 1.0 and 7.2. The distribution of the number of teeth lost was skew,
      indicating that a minor group of subjects had a substantially higher risk of
      tooth loss than the majority. Logistic regression analysis identified six
      significant predictors of tooth loss among those who remained dentate: age, a
      high number of teeth with dentinal caries lesions, a high number of teeth with
      caries lesions of any type, presence of teeth with attachment loss > or = 7 mm,
      presence of mobile teeth, and a low percentage of sites with subgingival calculus
      deposits. At the subject level, caries variables and periodontal disease
      variables seemed equally important predictors of the incidence of tooth loss over
      10 years, but at the tooth level caries was a predominant cause of tooth loss in
      all age groups.

PMID- 9192151
TI  - A comparison of patient satisfaction and dentist evaluation of overdenture
      therapy.
AB  - It has been argued that the retention of some teeth in the jaws as overdenture
      abutments prevents negative feelings about the loss of natural teeth. This study
      set out to evaluate how satisfied a group of patients were with wearing
      overdentures, and to compare their subjective evaluations with those of a dentist
      using objective criteria to examine the prostheses. A questionnaire was developed
      using questions adapted from several other studies. It was pretested, modified
      and used on all patients who were members of a longitudinal study of overdentures
      that started in 1974, and who returned on recall. At the end of 9 months, 101
      subjects had completed the questionnaire and examination. The mean age of the
      patients was 65.9 years with an age range of 35 to 88 years. There were 68 men
      and 33 women in this study and 62 of them were satisfied with their dentures; 33
      were satisfied, but felt they had some faults. Only 6 were unhappy about wearing
      the overdentures. The average length of time the dentures had been worn was 6.9
      years, with a range of 1 to 15 years. The most frequent complaints were loss of
      retention (65.4%) and discomfort (62.2%) of the mandibular dentures. A number of
      correlations were evaluated and some significant relationships were found between
      dentist and patient evaluation of the dentures. The best predictor of patient
      satisfaction with denture wearing was the patient's perception of retention and
      appearance. In the maxilla the patient's ability to chew and the dentist's
      evaluation of occlusion were also significant predictors. In the mandible the
      only other factors apart from retention and appearance were patient comfort and
      age.

PMID- 9192150
TI  - A comparison of the subjective oral health status of older adults from deprived
      and affluent communities.
AB  - A comparative study of the subjective oral health status of 60-65-year-old
      residents was undertaken in two Liverpool electoral wards, Vauxhall, the most
      deprived, and Woolton, the most affluent in the city. The measuring instrument
      used was the Subjective Oral Health Status Indicators (SOHSI) questionnaire
      devised by Locker. The questionnaire was administered by post to random samples
      of 250 residents from each ward. The main aim of the study was to compare the
      reported impact of oral conditions on the lives of individuals living in deprived
      and affluent communities. Responses of 59.6% for the deprived ward and 77.7% for
      the affluent ward were achieved. The literature suggested that significant
      differences could be expected between the wards in the reporting of subjective
      impact. However, significantly greater impact for only one functional sub-scale
      and one psycho-social sub-scale was reported by residents from the deprived ward.
      Further analysis of the relationship between impact and socio-demographic
      variables revealed a strong association between self-reported general health
      status and the subjective oral health indicators. Finally, a stepwise regression
      analysis found that pain and chewing problems were the only significant
      predictors of psycho-social impact. This finding confirms that the individual's
      socio-economic circumstances are of secondary importance to pain and functional
      problems in determining the psycho-social effects of oral conditions, as
      predicted by the conceptual model on which the measuring instrument is based.

PMID- 9192152
TI  - Understanding decision-making processes for sugar consumption in adolescence.
AB  - The mechanisms by which adolescents make food choices are not clear. The
      interaction and combination of the many social and psychological factors must be
      considered when examining adolescents' decision-making processes for sound food
      choices. The aim of this investigation is to examine one specific food choice,
      namely, the use of sucrose in hot drinks. One hundred and eighty-seven
      adolescents in their 16th year completed a questionnaire on the consumption of
      sugar using the method developed by AJZEN & FISHBEIN in their 'Theory of Reasoned
      Action'. The group was randomly divided into two groups so that decision-making
      processes with respect to two behavioural intentions-adding sugar to tea and
      coffee and excluding it-could be examined. The findings suggest that the
      immediate pleasurable taste of sugar outweighed and deferred the recognition of
      dangers associated with its consumption. Past dental health experiences,
      behaviours and education together with the role of parental figures acted as
      important influences. An awareness of these factors should assist dental health
      professionals to highlight the importance of sound food choices when negotiating
      dental health goals with adolescents.

PMID- 9192153
TI  - Antecedents of dental anxiety: learned responses versus personality traits.
AB  - The origins of dental fear and anxiety are numerous and complex. The purpose of
      the present study was to evaluate the relative effects of learned responses and
      subjective personality traits on the development of dental anxiety. The study was
      carried out in kibbutzim (closed homogeneous societies) in Israel where all
      subjects had received dental treatment from the same dentist since childhood with
      no choice of dentist. Subjects were requested to fill out questionnaires
      concerning their dental anxiety (DAS) in the past and at present, an evaluation
      of their dentist in the past and at present, and a psychopathologic symptom
      survey (SCL-90). The results show that dental anxiety at present correlates
      significantly with the evaluation of the present dentist; with dental anxiety as
      remembered from childhood; and with the following SCL-90 scales: interpersonal
      sensitivity, anxiety, phobic anxiety and Positive Symptom Distress Index. The
      best predictors of dental anxiety at present were the evaluation of the present
      dentist and past dental anxiety (as remembered from childhood). The results
      suggest that the level of the subject's dental anxiety is affected by
      environmental factors (evaluation of the present dentist, memories of anxiety
      from childhood), and by personality traits as evaluated by the SCL-90
      questionnaire.

PMID- 9192154
TI  - Electronic diagnosis of occlusal caries in vitro: adaptation of the technique for
      epidemiological purposes.
AB  - Most studies on electronic diagnosis of occlusal caries have involved taking site
      specific conductance measurements. Airflow around the electronic caries monitor
      probe removes superficial moisture and the conductance measurement reflects the
      caries status of that part of the fissure beneath the probe tip. This is an
      appropriate technique for a clinician to use to monitor caries status, and it
      could be adapted for use in epidemiological studies and clinical trials. The
      present work investigated an alternative technique using a jelly as a contact
      medium over the entire fissure system so that the probe might record the overall
      caries status of the tooth reflecting the worst affected site. Readings were
      taken on 96 extracted teeth with dye-coloured jelly acting as a contact medium.
      Readings were repeated on 32 teeth. Histological validation of caries status was
      carried out by visual examination of serial sections through each tooth to note
      the deepest lesion. The sensitivity and specificity of the overall electronic
      caries monitor readings were calculated for all lesions and dentine lesions only
      using selected resistance cut-off points and presented as a series of Receiver
      Operating Characteristic (ROC) curves. The optimum sensitivity and specificity
      values were, for all lesions: 61% and 86%, and for dentine lesions: 76% and 76%
      respectively. The reproducibility of the readings was acceptable (Kappa values
      for all lesions = 0.76, for dentine lesions = 0.55). The technique warrants
      further study as an overall reading may be more appropriate for epidemiological
      and clinical trial use.

PMID- 9192155
TI  - Radiographic criteria employed to diagnose and treat approximal caries by final
      year dental students in Mexico City.
AB  - A total of 407 final-year dental students in Mexico City were asked about the
      radiographic criteria they employed when assessing treatment needs for caries in
      a standardized patient case. 45.2% of participants would restore lesions confined
      to enamel; 60.7% believed that a lesion which had not passed the dentino-enamel
      junction would cavitate; and 65.4% said it would take on average 6 months or less
      for a lesion to progress from outer enamel to the dentino-enamel junction.
      Radiographic criteria appeared to reflect fears of rapid, inevitable progression
      of lesions. While local caries experiences had been reported to be high, there
      seems to be room for re-evaluating some clinical criteria employed to manage
      caries.

PMID- 9192156
TI  - A 48-month survival analysis comparing sealant (Delton) with fluoride varnish
      (Duraphat) in 6- to 8-year-old children.
AB  - The objective of this study was to compare Delton visible-light fissure sealant
      with Duraphat fluoride varnish in the prevention of occlusal caries in permanent
      first molars. A 48-month clinical trial was carried out in three groups of 6- to
      8-year-old schoolchildren: a sealant group (104 children), in which Delton was
      used; a varnish group (112 children), in which Duraphat was used; and a control
      group (128 children). Sealant or varnish was applied to all sound permanent first
      molars, according to group. Replacement (sealant) and reapplication (varnish) was
      carried out every 6 months. A survival analysis was used to describe the molar
      failures over time in the three groups. A Cox proportional hazards regression
      model was built to test the influence of group on molar failure. The median
      survival times were 28.6 months for the control molars and more than 48 months
      for both sealed and varnished molars. The Cox model indicated a hazard ratio of
      0.177 for the sealant vs control comparison, 0.463 for varnish vs control and
      0.382 for sealant vs varnish.

PMID- 9192158
TI  - The functional status of the masticatory system of 11-16-year-old adolescents:
      classification and validity.
AB  - Epidemiological studies to assess the prevalence and course of functional
      disturbances of the masticatory system should be based on a valid and reliable
      measure of the functional status of the masticatory system. NIELSEN et al. (2, 3)
      proposed a classification method that included three different classes of
      dysfunction. This classification was used to compare the results of a sample of
      447 11-16-year-old Swiss adolescents with those of the Danish study and to test
      the validity of this classification method. The two studies showed similar
      prevalences in two of the three dysfunction classes and a similar pattern of
      dysfunction categories. Concurrent and construct validity analyses showed
      significant correlations between the assessment from clinical examination and the
      subjective judgments of the adolescents. The results demonstrated cross- and
      concurrent validation of the "Nielsen index" but also stressed the necessity of a
      careful re-evaluation of the "severe" class criterion. The limitations of the
      Nielsen index led to the construction of a "Zurich-MAP index". The potential
      applications of both indices are discussed.

PMID- 9192157
TI  - Two types of intraoral distribution of fluorotic enamel.
AB  - Different distributions of fluorotic dental enamel within the dentition have been
      described in the literature. This report describes two patterns of intraoral
      distribution. In nine Tanzanian low fluorosis communities with a prevalence of
      pitting fluorosis of less than 2% and in five moderate fluorosis communities with
      a prevalence of pitting fluorosis of 16-59%, incisors and first molars were the
      least affected teeth. In four high fluorosis communities with a prevalence of
      pitting fluorosis of 86-97%, maxillary incisors exhibited lower Thylstrup
      Fejerskov Index values than the maxillary canines, premolars and molars. The
      mandibular teeth exhibited increasing Thylstrup-Fejerskov Index values from the
      anterior to the posterior region. The curves presenting the intraoral
      distribution of the severity of dental fluorosis corresponded with the curve
      presenting the completion time of primary enamel formation of the various tooth
      types, with the exception of the first molars in high fluorosis communities. The
      similarity of the curves suggests that the later in life enamel is completed, the
      higher is the severity of dental fluorosis. This relation seems to be explained
      by the prevailing feeding and dietary habits, which result in minimal intake of
      fluoride in the first 18 months of life during breastfeeding, followed by
      increasing fluoride ingestion in the following years through consumption of tea,
      seafish and F-containing magadi salt.

PMID- 9192159
TI  - Menadione-induced oxidative stress accelerates onset of Emory mouse cataract in
      vivo.
AB  - PURPOSE: We evaluated the effect of the free-radical generator, menadione, on the
      time of occurrence of cataract in the Emory mouse, a model for human cataract.
      Concomitant experiments were done to compare production and level of reactive
      metabolites of oxygen in the Emory mouse and its cataract resistant (CR) genetic
      control. METHODS: Test and control mice were fed both a normal diet and a diet
      supplemented with menadione, and the lenses were evaluated for the time of
      occurrence of cataract and the level of membrane ATPases. Effects of menadione
      were determined on incubated lenses of Emory and CR mice, assaying reactive
      species of oxygen, levels of antioxidant enzymes, and formation of the lipid
      peroxidation product, malondialdehyde. RESULTS: Systemic administration of
      menadione markedly accelerated the onset of Emory mouse cataract, and decreased
      ATPase activities suggested oxidative damage to membrane proteins. Cumulative
      levels of O2.-, H2O2, .OH and malondialdehyde were significantly higher than
      controls in the lenses incubated in the presence of menadione, showing that it
      generates oxidative stress. However, [GSH] in lenses decreased equally in test
      and control mice. The observed increases in catalase and glutathione peroxidase
      activities in the test lenses indicated an early protective response to oxidative
      insult. CONCLUSIONS: Acceleration by menadione of the appearance of cataract in
      the Emory mouse demonstrates that oxidative stress is a risk factor in late-onset
      cataract. This quinone caused a greater increase in the production and levels of
      reactive metabolites of oxygen in Emory mice than in CR mice, indicative of a
      higher susceptibility of the former to oxidative insult.

PMID- 9192160
TI  - Regional glycoprotein expression in the chicken lens.
AB  - PURPOSE: Several previous studies have shown that glycoconjugates of
      extracellular matrix, cell membrane and nucleus play an important role in the
      mediation of cell proliferation, migration and differentiation. Lens epithelial
      cells and lens fiber cells show regional differences with regard to these
      parameters. If glycoconjugates participate in the regulation of these patterns in
      the lens, there should be regional differences in the expression of
      glycoconjugates. The investigation was focused on the anterior pole, equator and
      nuclear bow regions, which differ extensively in lens cell proliferation and
      differentiation. METHODS: To check this hypothesis, the regional binding pattern
      of twelve different FITC-conjugated lectins was studied glycohistochemically,
      using paraffin embedded material. The investigation was focused on the anterior
      pole, equator and nuclear bow regions. RESULTS: Regional differences in lectin
      binding patterns were identified in the lens capsule, epithelium and the nuclear
      bow regions. The lens capsule was fluorescently labeled with GS-I, UEA-I, LPA,
      MAA, SNA only at the anterior pole and with CON-A, WGA, DBA, SBA only at the
      equator. Staining of the entire anterior surface of the lens capsule was observed
      with LFA. Cell membranes of the lens epithelium showed binding of MAA and LFA
      only at the equator. LFA, LPA, MAA and SNA only stained the nuclei of fiber cells
      at the nuclear bow region but not of lens epithelial cells. WGA strongly labeled
      the nuclei of equatorial epithelial cells and fiber cells at the bow region.
      CONCLUSIONS: It is assumed that the observed regional variations in glycoprotein
      expression in the extracellular matrix and lens cells contribute to the
      regulation of cell behavior in different areas of the lens.

PMID- 9192161
TI  - Changes in corneal and lens autofluorescence and blood glucose levels in
      diabetics: parameters of blood glucose control.
AB  - PURPOSE: We investigated corneal and lens autofluorescence in patients with
      proliferative diabetic retinopathy (PDR) to determine a correlation between the
      two parameters and blood glucose levels and HbA1c. METHODS: Corneal and lens
      autofluorescence levels in 17 PDR patients and 8 healthy controls were measured
      with a fluorophotometer fitted with an anterior segment adapter. We measured the
      lower blood glucose level (BS1), corneal autofluorescence (CA1), and lens
      autofluorescence (LA1) simultaneously and the higher blood glucose level (BS2),
      CA2, and LA2 simultaneously on the same day. We defined parameter changes as:
      delta BS = BS2 - BS1, delta CA = CA2 - CA1, and delta LA = LA2 - LA1. RESULTS:
      Corneal and lens autofluorescence significantly increased in the patients,
      compared with the controls (p < 0.001). Lens autofluorescence had a significant
      positive correlation with HbA1c (r = 0.656, p < 0.01) in the patients. delta CA
      (ngEq/ml) correlated significantly with delta BS (mg/dl) (r = 0.631, P < 0.01).
      CONCLUSIONS: Results suggest that lens autofluorescence might represent the long
      term control of diabetes, and corneal autofluorescence levels may represent short
      term changes in the blood glucose level, because hyperglycemia accelerates with
      increasing corneal autofluorescence in PDR patients. Corneal and lens
      autofluorescence may be related to the breakdown of the blood-aqueous barrier.

PMID- 9192162
TI  - A genetic basis for corneal sensitivity to ultraviolet light among recombinant
      SWXJ inbred strains of mice.
AB  - PURPOSE: To examine a possible genetic basis for corneal sensitivity to UV-B
      light exposure. METHODS: To this end, adult male mice from the 14 SWXJ
      recombinant inbred albino strains (originating from SJL/J and SWR/J parental
      strains) were subjected to ultraviolet (UV) radiation exposure of 0.078 J/cm2 and
      photographed four days post-exposure, to assess corneal opacity and the possible
      correlation with corneal aldehyde dehydrogenase (ALDH) activity, alcohol
      dehydrogenase (ADH) activity and soluble protein content. RESULTS: Those
      recombinant strains that exhibited the SWR/J strain phenotype of having low
      levels of ALDH and decreased soluble protein levels also exhibited greater levels
      of corneal clouding after UV-exposure than the other strains, which exhibited
      "normal" levels of both ALDH activity and soluble protein in the cornea.
      CONCLUSIONS: These data support an hypothesis for a major role for ALDH in
      assisting the cornea to protect the eye against UV-induced tissue damage.

PMID- 9192163
TI  - Selective IL-10 inhibition of HLA-DR expression in IFN-gamma-stimulated human
      retinal pigment epithelial cells.
AB  - PURPOSE: Human RPE cells express HLA-DR antigens, bind leukocytes via ICAM-1, and
      secrete IL-8 and MCP-1, which attract and activate leukocytes. Since little is
      known concerning endogenous cytokines that may alter ocular immunologic and
      inflammatory mechanisms, we investigated whether IL-10, an immunosuppressive
      cytokine, modulates these HRPE features. METHODS: IL-10 effects on HLA-DR and
      ICAM-1 were examined by HRPE exposures to: (1) IFN-gamma (10-1000 U/ml) + IL-10
      (1-100 U/ml) and (2) IL-10 pre-incubation followed by IFN-gamma + IL-10.
      Immunohistochemistry for HLA-DR and ICAM-1 was graded by masked observers. Flow
      cytometric analysis quantitated HRPE HLA-DR and ICAM-1. Effects of IL-10 on IL-1
      beta (0.2 or 2 ng/ml)-, or TNF-alpha (0.2 or 2 ng/ml)-induced IL-8 and MCP-1
      secretion and gene expression were assessed using enzyme-linked immunosorbent
      assay (ELISA) and Northern blot analysis. RESULTS: HLA-DR expression, detected by
      immunohistochemistry and flow cytometric analysis, showed dose-dependent
      increases to IFN-gamma. IL-10 pre-/co-incubation, but not co-incubation alone,
      markedly reduced HLA-DR expression, but did not modulate constitutive or IFN
      gamma-induced ICAM-1. IL-10 alone did not induce MCP-1 or IL-8 secretion or
      steady-state mRNA expression, nor modulate IL-1 beta-, TNF-alpha- or IFN-gamma
      induced IL-8 or MCP-1. CONCLUSIONS: This study suggests that HRPE HLA-DR antigens
      are selectively inhibited by IL-10, but the timing of IL-10 exposure may be
      crucial.

PMID- 9192165
TI  - Cysteine and ascorbate loss in the diabetic rat lens prior to hydration changes.
AB  - PURPOSE: Glutathione (GSH) loss precedes vacuole formation in the diabetic rat
      lens, but the cause of this loss is not known. Cysteine availability is a rate
      limiting factor to glutathione biosynthesis in rat and human lenses but its
      concentration is not known; therefore free cysteine was measured prior to lens
      hydration in the diabetic rat lens. GSH can regenerate ascorbate from
      dehydroascorbate within the lens and potentially modulate the ascorbate pool;
      therefore ascorbate loss is also a possibility that has not been examined
      previously. METHODS: Diabetes was induced in Wistar rats to provide a slowly
      progressing model of cortical cataract. Age-matched control rats were injected
      with buffer vehicle only. Lens condition was monitored by binocular slit-lamp
      microscope after pupil dilation. Lens cysteine and glutathione were measured in
      the same lens, while ascorbate and total ascorbate (ascorbate + dehydroascorbate)
      of the contralateral lens were quantified by high performance liquid
      chromatography electrochemical detection. The 1- and 2-week periods of diabetes
      were chosen as they both preceded lens hydration changes and Na+/K+ changes, to
      avoid leakage due to ruptured cell membranes. RESULTS: Lens weights were not
      significantly different compared to controls at either the 1- or 2-week periods,
      and lenses were completely free of initial vacuole formation. Lens GSH
      concentration was diminished by 72% compared with controls after 1 week of
      diabetes and 74% after 2 weeks of diabetes. Lens free cysteine was decreased by
      62% and 78% compared with controls after 1 and 2 weeks of diabetes, respectively.
      Total lens ascorbate concentration was decreased by 34% after 1 week of diabetes
      and 48% after 2 weeks of diabetes. Dehydroascorbate levels represented less than
      10% of the total lens ascorbate pool in all experimental groups. GSH and
      ascorbate concentration were correlated after 1 week of diabetes (p < 0.005) and
      after 2 weeks of diabetes (p < 0.001). GSH and cysteine concentration were also
      correlated after 1 week of diabetes (p < 0.001) and after 2 weeks of diabetes (p
      < 0.001). CONCLUSIONS: Decreased free cysteine, in the diabetic rat lens,
      precedes hydration changes and vacuole formation, contributing to decreased
      glutathione content. While cysteine was not abundant in the lens, its
      concentration is greater than previously supposed. The lens ascorbate pool was
      also diminished prior to lens hydration.

PMID- 9192164
TI  - Porcine model of proliferative vitreoretinopathy with platelets.
AB  - PURPOSE: To develop an experimental model of proliferative vitreoretinopathy
      (PVR) in the pig, and determine the efficacy of platelet-derived growth factor
      (PDGF) compared with different platelet plasma concentrates in its development.
      METHODS: Animals were divided into four groups of 12 pigs each. Group 1, 2, and 3
      underwent four 3-mm-long retinotomies, a partial mechanical vitrectomy, and six
      transconjunctival retinal cryoapplications and were injected intravitreally with,
      respectively, 0.2 ml of platelet rich plasma, 0.2 ml of a solution containing 200
      ng of porcine PDGF, and 0.2 ml of platelet concentrated plasma. Group 4 received
      only an intravitreal injection of 0.2 ml of porcine PDGF. RESULTS: In Group 1,
      retinal detachments (RDs) developed in six eyes (50%) (two eyes, total RDs; four,
      extensive RDs). In Group 2, focal RDs developed in six eyes (50%). In Group 3, 11
      eyes (92%) developed Rds (six eyes, total RDs; three, extensive RDs, two, focal
      RDs). Group 4, did not develop lesions. Statistically significant differences
      were found between Group 3 and the other groups. Group 2 RDs were associated with
      the presence of vitreoretinal membranes but there were no signs of PVR. In Groups
      1 and 3, signs of anterior PVR, posterior PVR, and retinal holes with rolled
      edges were observed. CONCLUSIONS: We have developed a model of PVR in the pig,
      the retina of which more closely resembles that of humans. Platelet plasma more
      effectively contributed to the development of an experimental model of porcine
      PVR than 200 ng of PDGF. The efficacy depends on the platelet concentration of
      the plasma. These results suggest that other growth factors and plasma components
      may interact synergistically with PDGF in the pathogenesis of PVR.

PMID- 9192166
TI  - Effect of mitomycin-C on human retinal pigment epithelium in culture.
AB  - PURPOSE: To determine the effect of mitomycin-C on confluent and non-confluent
      human retinal pigment epithelium (RPE) in tissue culture. METHODS: The effect of
      mitomycin-C on confluent RPE was determined by treating first passage confluent
      cells with 0.01, 0.1, 1, 10, 100 or 1000 micromolar (microM) mitomycin-C for 1,
      3, or 7 days. The cell viability after treatment was determined by using an
      esterase stain. The effect of mitomycin-C on proliferating RPE was determined by
      incubating non-confluent cells with the above concentrations of mitomycin-C for
      20 min, 1 hour or 24 hours. RESULTS: Mitomycin-C can be toxic to a confluent RPE
      monolayer, and the LD50 is 421, 28.8 or 0.0632 microM when cells are continually
      exposed to mitomycin-C for 1, 3 or 7 days, respectively. Exposure to mitomycin-C
      at concentrations > or = 10 microM for 20-60 min significantly inhibits
      proliferation of non-confluent RPE. A 24 hour exposure of RPE to 1 microM
      mitomycin-C markedly inhibits proliferation of non-confluent RPE with minimal
      toxicity to confluent RPE. CONCLUSIONS: Since exposure of human RPE to mitomycin
      C for 24 hours can inhibit cell proliferation at concentrations which are well
      tolerated by confluent RPE, mitomycin-C may be a suitable agent for inhibiting
      RPE proliferation in vivo.

PMID- 9192167
TI  - Diurnal variations in tear glycoproteins: evidence for an epithelial origin for
      the major non-reducible > or = 450 kDa sialoglycoprotein(s).
AB  - PURPOSE: To characterize the nature and origin of changes in tear glycoproteins
      accompanying eye closure. METHODS: Reflex (R) and overnight closed (C) eye tears
      collected by capillary tubes were centrifuged with the resulting R pellets
      (primarily desquamated epithelial cells) and C pellets (primarily PMN and some
      epithelial cells) extracted in acidic PBS. Extracts and supernatants were
      separated by size-exclusion HPLC and/or SDS-PAGE. Gels were stained or blotted
      and immune- or lectin-probed. An HPLC glycoprotein fraction of > or = 450 kDa
      isolated from all four sources was characterized before and after partial
      deglycosylation, using antibodies specific to known mucin and carbohydrate
      epitopes. Immunofluorescence microscopy was carried out on human conjunctiva,
      using as probe a MAb to salivary mucin specific for a sialyl Lea epitope, which
      was found to cross-react specifically with the major non-reducible high molecular
      weight sialoglycoproteins (SGs) in tears. These SGs were immunoprecipitated and
      blot-probed along with tissue extracts. RESULTS: R fluid contained minor amounts
      of numerous glycoproteins, including probably several of inducible lacrimal
      secretory origin. Results confirmed sIgA as the principal source of the intense
      reducible glycoprotein bands common to C fluid. Smaller amounts of free secretory
      component and serum glycoproteins were also visualized. The HPLC fraction (> or =
      450 kDa) consisted of four major non-reducible glycoproteins. In R fluid, this
      fraction (< 1% total protein) consisted primarily of two entities: a 450-500 kDa
      SG and a larger asialoglycoprotein. The SG accounts for as much as 85% of the
      total protein in the R pellet extract. C fluid was associated with a selective
      increase in SGs and a shift in distribution to two SGs > 500 kDa. All SGs
      exhibited a common antigenicity reacting specifically with the MAb for the sialyl
      Lea epitope. SGs indistinguishable in size and antigenicity were recovered in
      epithelial extracts. Immunofluorescence microscopy revealed that reactivity was
      localized to the epithelial plasma membrane, increasing in intensity from basal
      to apical cells. Although these SGs exhibited some properties in common with
      MUC1, immunological and other data suggest a unique SG. CONCLUSIONS: Tear
      glycoproteins are derived from four principal sources. In R fluid, an inducible
      lacrimal secretion predominates. In C fluid, a constitutive sIgA secretion
      predominates, augmented by a serum exudate and SGs derived at least in part from
      the epithelium. In R fluid and pellet extracts, the SGs consist primarily of a
      450-500 kDa species that is most probably derived from the plasma membrane.
      Larger antigenically related SGs are prevalent in C fluid.

PMID- 9192168
TI  - Determination of ascorbic acid in human vitreous humor by high-performance liquid
      chromatography with UV detection.
AB  - PURPOSE: Ascorbic acid (AA) accumulates in vitreous at a concentration several
      times higher than in plasma. It has been suggested that AA may serve as an
      antioxidant that protects ocular tissues from free radical attack. There are many
      reports about the concentration of AA in ocular tissues. However, AA in adult
      human vitreous humor has not been determined. We measured concentrations of AA
      from pathologic human vitreous samples and compared the results. METHODS: AA was
      measured by high-performance liquid chromatography (HPLC) with UV detection.
      Human vitreous humor was collected from patients undergoing pars plana
      vitrectomy. RESULTS: AA was quantified in vitreous humor of proliferative
      diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), macular hole
      (MH), idiopathic premacular fibrosis (PMF), and Terson syndrome (Terson). The
      concentrations of AA were 120.9 +/- 36.3 micrograms/ml (mean +/- SD), 129.8 +/-
      36.6, 311.5 +/- 126.7, 446.9 +/- 154.2 and 406.0 +/- 22.0, respectively. There
      was no significant difference between the PDR and the PVR groups (unpaired t
      test). Patients with PDR and PVR showed significantly lower concentrations of AA
      than those with MH, PMF, and Terson (p < 0.01). CONCLUSIONS: These findings
      suggest that increased oxidative stress may be produced in the ocular tissues of
      eyes with PDR and PVR, and AA appears to be consumed (oxidized) in performing its
      protective role.

PMID- 9192169
TI  - Effects of aldose reductase inhibitor CT-112 on the corneal epithelial barrier of
      galactose-fed rats.
AB  - PURPOSE: To investigate whether the barrier function of the corneal epithelium is
      disrupted in galactosemic rats, and to assess the effects of the aldose reductase
      inhibitor CT-112, in the form of eyedrops, on the corneal epithelial barrier in
      galactosemic rats. METHODS: Forty rats were divided into 3 groups based on their
      diet: a control group, a galactose group and a CT-112 treated galactose group (CT
      112 group). After 3 weeks, 31 rats from the 3 groups were subjected to
      fluorophotometry, in which fluorescein (F) was instilled into one eye and
      carboxyfluorescein (CF) was instilled into the other eye in a random fashion. The
      F and CF uptakes were then measured at the central cornea by a slit-lamp
      fluorophotometer. Three rats from each group were exposed to a horseradish
      peroxidase (HRP) solution for one hour, and the HRP-reactive substances within
      the corneal epithelium were also examined via electron microscopy. RESULTS: There
      was significantly higher F uptake in the galactose group than in the control (p =
      0.003) and CT-112 groups (p = 0.028). There were no significant differences in CF
      uptake between the 3 groups. Histologically, HRP-reactive substances were found
      in much greater quantities within the superficial corneal cells of the galactose
      group than in the control or CT-112 groups. CONCLUSIONS: These results suggest
      that cell membrane disruption, as detected by F uptake and HRP penetration, was
      found in the superficial corneal cells of galactose-fed rats, and that
      intercellular junction integrity can be assayed by CF uptake and histological
      evaluation. Moreover, CT-112 eyedrops were effective in improving the corneal
      epithelial barrier dysfunction of galactose-fed rats.

PMID- 9192170
TI  - Histidine-like immunoreactivity in the rat retina.
AB  - PURPOSE: Histidine is an indispensable amino acid with an imidazole ring and it
      is a precursor of histamine, carnosine, and anserine. Histidine has been proposed
      to act as a neurotransmitter or neuromodulator in mammalian central nervous
      system (CNS), including retina. In this study, we report histidine-like
      immunoreactivity in the rat retina with the use of antibodies raised against
      histidine coupled to bovine serum albumin (BSA) with glutaraldehyde. METHODS: In
      order to confirm the specificity of the antiserum toward histidine, immunodots
      were carried out. Only the histidine conjugate showed immunoreactivity. The rat
      retinas fixed with glutaraldehyde were used for immunocytochemistry. RESULTS:
      Histidine immunoreactivity was identified in the ganglion cell layer (GCL), inner
      nuclear layer (INL), inner plexiform layer (IPL), and Muller cells of rat retina.
      CONCLUSIONS: Histidine may be a precursor of histamine in the inner retina, and
      Muller cells may play some role in the metabolism of histidine.

PMID- 9192171
TI  - Keratocyte migration and peptide growth factors: the effect of PDGF, bFGF, EGF,
      IGF-I, aFGF and TGF-beta on human keratocyte migration in a collagen gel.
AB  - PURPOSE: Peptide growth factors are known accelerators of corneal wound healing,
      probably mediated through increased proliferation of the cells; however,
      information about their effect on keratocyte motility is lacking. The influence
      of peptide growth factors on keratocyte migratory activity was investigated,
      using the following growth factors: platelet derived growth factor (PDGF-BB),
      epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), basic
      fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I) and
      transforming growth factor-beta-1 (TGF-beta 1). METHODS: Keratocytes were seeded
      on gels of type 1 collagen, growth factor added, and the cells left to migrate
      for 72 hours. Subsequently, the number of keratocytes at the different levels in
      the collagen gel was evaluated by optically sectioning the gel at 20 microns,
      intervals, with an inverted phase contrast microscope. RESULTS: PDGF, EGF and
      bFGF at 10 ng/ml, all increased the number of keratocytes at the different levels
      of the gel as compared to a non-stimulated control (p < 0.05 or p < 0.01,
      students t-test). TGF-beta proved to be a strong inhibitor of keratocyte
      migration, decreasing the number of keratocytes observed at every level in the
      gel (p < 0.05 and p < 0.01, students t-test), whereas no effect of IGF-I and aFGF
      was found. During the 72 hours of migration, no contraction of the collagen gels
      was observed. Autoradiography of histological sections of the gels showed that
      during the 72-hour period only TGF-beta and 10% fetal bovine serum induced an
      increase in keratocyte proliferation. CONCLUSION: PDGF, EGF and bFGF increase
      keratocyte migration, independent of proliferation in a collagen gel invasion
      assay and might promote corneal wound healing, not only by increasing cell
      proliferation, but also through increased motility.

PMID- 9192172
TI  - M3 muscarinic receptor mediates regulation of protein secretion in rabbit
      lacrimal gland.
AB  - PURPOSE: To identify which muscarinic receptor subtypes mediate protein secretion
      in isolated rabbit lacrimal glands. To compare protein secretory profiles in
      vitro with those in rabbit tears. METHODS: Rabbit lacrimal gland slices were
      incubated with carbachol in the presence and absence of different muscarinic
      antagonists. Protein secretion into the incubation medium was characterized with
      a Bio-Rad protein assay dye reagent in conjunction with Laemmli's method of SDS
      PAGE. The medium protein profile was compared to that in tear samples. RESULTS:
      Dose dependent increases in protein secretion were elicited by carbachol between
      10(-7) and 10(-4) M. During the first 20 min period, a maximal increase of 64%
      above the basal level was seen at the highest concentration. With 10(-4) M
      carbachol, the response was transient because after 100 min it decreased to its
      basal level. The increases in protein secretion caused by 10(-4) M carbachol were
      completely suppressed in the presence of 10(-5) M atropine. On the other hand,
      the relatively selective M1 antagonist, pirenzepine, at concentrations from 10(
      6) M to 10(-4) M, had no effect on either the basal levels or the stimulatory
      effects of carbachol. Similarly, the relatively selective M2 antagonist,
      gallamine, at concentrations from 10(-6) M to 10(-4) M, had no effect on either
      of these levels. In contrast, the relatively selective M3 antagonist, 4-DAMP, at
      concentrations from 10(-6) M to 10(-4) M, progressively suppressed the stimulated
      level of protein secretion elicited by 10(-4) M carbachol without affecting the
      basal level. The protein profiles found in the tears and in the incubation medium
      were similar to one another. CONCLUSION: In vitro rabbit lacrimal gland protein
      secretion is comparable to that in vivo. Cholinergic-mediated control of rabbit
      lacrimal gland protein secretion occurs through stimulation of the M3 muscarinic
      receptor subtype.

PMID- 9192173
TI  - Fluorescent Gram stain in the microbiologic diagnosis of infectious keratitis and
      endophthalmitis.
AB  - PURPOSE: To verify the sensitivity of a recently described technique of
      fluorescent Gram stain (FGS) and evaluate its role in direct microscopic
      examination of clinical ocular samples. METHODS: In the first part of the study,
      culture suspensions of 10 bacterial isolates were stained, using FGS and
      conventional Gram stain (CGS), and were assessed for morphology, and Gram sign.
      In the second part, 39 corneal scrapings and 18 vitreous biopsy materials were
      stained and observed by both methods. RESULTS: Gram reaction and morphology of
      the bacteria, using CGS and FGS, were compared against culture. In both parts of
      the study, the sensitivity of CGS was significantly higher than FGS in the
      detection of Gram positive reaction (p = 0.01, 0.02). The specificities and
      predictive values of CGS and FGS were comparable in the evaluation of clinical
      samples. The bacterial morphology was demonstrated better (p = 0.01) with CGS.
      Significant quenching of fluorescence and change in Gram reaction with time were
      noted in FGS. CONCLUSIONS: The low sensitivity, quenching of fluorescence and
      change in Gram reaction presently preclude the usage of FGS as a diagnostic tool
      in ocular infections.

PMID- 9192174
TI  - Regulation of iron metabolism in eukaryotes.
AB  - Iron metabolism is regulated in cells to ensure that iron supplies are adequate
      and nontoxic. The expression of iron metabolism is regulated primarily by
      posttranscriptional mechanisms. Ferritin, eALAS, SDHb of Drosophila, and
      mammalian mitochondrial aconitase are translationally regulated. The TfR is
      regulated at the level of mRNA stability. Iron regulatory proteins are regulated
      either by assembly or by disassembly of an iron-sulfur cluster (IRP1) or by rapid
      degradation in the presence of iron (IRP2). The list of targets for IRP-mediated
      regulation is growing longer, and a range of possibilities for versatile
      regulation exists, as each IRP can bind to unique targets that differ from the
      consensus IRE. The reactivity of iron with oxygen and the creation of toxic by
      products may be the evolutionary stimulus that produced this system of tight
      posttranscriptional gene regulation.

PMID- 9192175
TI  - Structure, mechanism, and specificity of protein-tyrosine phosphatases.

PMID- 9192177
TI  - Aging and regulation of apoptosis.
AB  - When Lockshin and Zakeri discussed the relevance of apoptosis to aging, the
      common view was that apoptosis had primarily a negative impact on aging by
      destroying essential and often irreplaceable cells. That view has now changed to
      one that acknowledges that there are two general ways in which apoptosis can play
      a role in aging: (1) elimination of damaged and presumably dysfunctional cells
      (e.g., fibroblasts, hepatocytes) which can then be replaced by cell
      proliferation, thereby maintaining homeostasis and elimination of essential
      postmitotic cells (e.g., neurons) which cannot be replaced, thereby leading to
      pathology. Evidence exists in two systems (fibroblasts and
      thymocytes/lymphocytes) that there are age-related decreases in the potential for
      apoptosis, although the molecular bases for these decreases appear to differ
      (Table II). Fibroblasts (and neurons?) lose the ability to downregulate bcl-2 in
      response to an apoptotic signal; thus, apoptosis is blocked even though an
      initiating signal has been received. In contrast, thymocytes/lymphocytes lack the
      ability to initiate the signal due to downregulation of the cell surface receptor
      Fas. There is limited information available for other tissue types, and nothing
      is known about why and how these age-related changes occur. An interesting
      observation, but not necessarily a critical one, is that the frequency of
      upregulation of the bcl-2 gene due to chromosome translocation increases with
      age. The role of apoptosis in regulating cell number is also a promising area of
      research. The studies on liver damage and neoplastic lesions suggest an extremely
      important role for apoptosis in controlling cancer. This may be particularly
      important in the prostate, where hypertrophy and cancer are a virtual certainty
      with ever-increasing age. It is not known whether the ability to undergo
      apoptosis declines in the prostate with increasing age, but it appears likely
      that it does. One problem in answering questions about the actual regulation of
      apoptosis is the lack of a quantitative assay. Apoptosis appears to be either
      "on" or "off" in cells, while the basic cell-killing machinery may often be
      present, but in an inactive form. Most assays for apoptosis are microscopic
      rather than kinetic, and the rate-limiting step may be at the level of the
      initiating signal. Thus, if CR, which extends the life span of rodents, does
      upregulate apoptosis, it is not clear how to quantify the magnitude of this
      effect or what should be quantified. The best one can do is to measure the
      frequency of occurrence of apoptotic bodies. This is essentially a pool size
      assay which provides little knowledge about how rapidly cells are leaving and
      entering the pool. Nevertheless, the results currently available do suggest that
      apoptosis is a process which may be important in aging, at least in some tissues,
      and the mechanism of its regulation needs to be understood. Although a variety of
      tumor suppressor gene and oncogene products are known to be involved in signal
      transduction associated with apoptosis, it remains to be shown which of these, if
      any, are actually involved in "on-off" switches for apoptosis and which might
      regulate the intrinsic rate of apoptosis. As Driscoll has already pointed out:
      "regulation and execution of cell death is an absolutely critical process that
      interfaces with nearly every aspect of life. Future investigation of the links of
      cell death to cellular aging and the aging of organisms should be an exciting
      enterprise."

PMID- 9192176
TI  - Regulation of Fas-mediated apoptosis.

PMID- 9192178
TI  - Gene regulation by reactive oxygen species.

PMID- 9192179
TI  - Regulation of NF-kappa B and disease control: identification of a novel serine
      kinase and thioredoxin as effectors for signal transduction pathway for NF-kappa
      B activation.
AB  - We have identified novel signal transduction cascades in activating NF-kappa B,
      as well as its pathogenetic roles in various disease processes. By applying the
      basic knowledge obtained through these studies, we hope to find new therapeutic
      measures against currently incurable diseases such as hematogenic cancer cell
      metastasis, rheumatoid arthritis, and AIDS. We also propose a novel strategy in
      screening effective inhibitors against transcription factors. Elucidation of the
      cis-regulatory element for expression of pathogenetic genes and identification of
      the responsible transcription factor will not only facilitate the study of
      pathogenesis but will also promote the development of effective therapy.
      Recognition of control mechanisms of the NF-kappa B activation pathway has
      explained the therapeutic efficacy of various compounds with different
      pharmacologic actions. A similar strategy may be applicable for other inducible
      transcription factors. From the medical point of view, one of the purposes of
      these approaches is to find small molecular weight compounds that can be
      administered orally and that are effective in controlling gene expression of
      pathogenetic genes.

PMID- 9192180
TI  - Regulation of bacterial responses to oxidative stress.

PMID- 9192181
TI  - Mechanism and regulation of bone resorption by osteoclasts.

PMID- 9192182
TI  - Effects of single and repeated administration of sulthiame on amygdaloid kindled
      seizures in rats.
AB  - In this study, we assessed the anti-convulsive effects of sulthiame (SUL) in
      amygdaloid (AM) kindled rats. Electrodes were implanted into the left AM of adult
      male Wistar rats. The animals were kindled at the after-discharge (AD) threshold.
      Upon completion of kindling, a generalized seizure triggering threshold was
      determined. The drugs were administered intraperitoneally in rats which
      reproducibly exhibited generalized convulsions at the near-threshold stimulation.
      Single administration of SUL (25-200 mg; n = 7-9) reduced the forelimb clonus
      (FCL) duration, but only the highest dose significantly regressed the secondarily
      generalized convulsion. During repeated administration of SUL, 50 mg/kg for 8
      days, FCL duration was significantly alleviated until the fifth treatment day.
      With the dose of 200 mg/kg, significant suppression of secondary generalization
      was noted only until the second test day. On the other hand, significant
      reductions of FCL and AD duration were preserved afterwards. The anti-convulsive
      effects of SUL indicated in this study were not comparable to those of other
      standard anti-epileptic drugs reported from our laboratory.

PMID- 9192183
TI  - Fos-immunoreactive responses in inferior colliculi of rats with experimental
      audiogenic seizure susceptibility.
AB  - Audiogenic seizure (AGS) susceptibility is a reflex epilepsy of rodents in which
      acoustic stimulation evokes wild running attacks and subsequent convulsions.
      Susceptibility can be induced in non-susceptible strains by treatments causing
      transient or permanent hearing losses as long as these occur during the neonatal
      period. The defect which is the basis of susceptibility has been proposed to be a
      failure of developmental organization of inferior colliculus (IC) into frequency
      selective zones. That is, high frequency stimuli evoke responses in broader
      arrays of neurons in ICs of susceptible rats than in those of neonatally
      untreated (non-susceptible) controls. Nonetheless, this observation has been made
      only in rats in which susceptibility was induced by exposure to intense noise on
      postnatal day (PND) 14. By contrast, the present study examines whether unusually
      broad topographic responses are also characteristic in ICs of rats made
      susceptible by the neonatal administration of low doses of the ototoxic
      antibiotic, kanamycin (KM). Patterns of Fos-like immunoreactivity (Foslir)
      induced by seizures or pure tone stimuli were compared in ICs of adult Wistar
      rats which neonatally had been (a) sham-treated; (b) noise-exposed on PND 14; or
      (c) injected on PNDs 9-12 with 100 mg/kg KM. It was found that sound-triggered
      seizures in the two experimental groups resulted in induction of Foslir primarily
      within cortical areas of IC. By contrast, pure tones evoked unusually broad
      responses in the central nucleus of ICs of both susceptible groups but not in
      those of controls. Additionally, in the KM-treated rats, the range of frequencies
      evoking abnormal responses extended one octave lower than was characteristic of
      noise-exposed rats. The earlier schedule of treatments in the KM model may
      account for this inasmuch as low frequency response domains undergo development
      at younger ages. The similarity of results in the two models suggests failure of
      development of frequency selective fields in IC is indeed the common basis of
      experimentally induced susceptibility to sound-triggered seizures.

PMID- 9192184
TI  - Longitudinal distribution of hippocampal atrophy in mesial temporal lobe
      epilepsy.
AB  - Patients with mesial temporal lobe epilepsy (MTLE) have asymmetric hippocampal
      volumes with atrophy that sometimes by visual inspection appears to favor
      different regions along the longitudinal axis of the affected hippocampus.
      Histological studies suggest that cell loss may affect the anterior hippocampus
      preferentially, and that hippocampal sclerosis (HS) limited to the anterior of
      the hippocampus may indicate better surgical outcome. We used volumetric magnetic
      resonance imaging (MRI): (1) to objectively describe the distribution of volume
      loss in HS; and (2) to relate this distribution to outcome of temporal lobectomy.
      Hippocampal volumes and anterior and posterior subvolumes (AHV, PHV) were
      measured from MP-RAGE MRI in 43 temporal lobectomy patients with MTLE determined
      by pathological findings of HS and compared to 23 age-matched controls. Atrophy
      was defined as 'anterior', 'diffuse', 'posterior', or 'normal' depending on
      position of AHV and PHV relative to the mean +/- 2 S.D. of regional volumes of
      control hippocampi. Anterior to posterior ratios (APR = AHV/PHV) were also
      calculated. Mean APR of hippocampi ipsilateral to lobectomy cannot be
      distinguished from hippocampi contralateral to lobectomy or from controls. AHV
      and PHV from hippocampi contralateral to temporal lobectomy were smaller than
      controls but larger than hippocampi ipsilateral to lobectomy. Surgical outcome
      was independent of longitudinal distribution of atrophy. We determined that
      overall volume loss in HS is diffuse, neither clearly favoring the head nor body
      tail. Surgical outcome for MTLE is not related to the longitudinal distribution
      of atrophy revealed by volumetric MRI.

PMID- 9192185
TI  - Post-ictal depression transiently inhibits induction of LTP in area CA1 of the
      rat hippocampal slice.
AB  - We tested the effects of electrographic seizures (EGSs) elicited in a remote site
      (area CA3) on the induction of long-term potentiation (LTP) in area CA1 of the
      rat hippocampal slice. Induction of LTP was inhibited only when the LTP-inducing
      stimulus was delivered during the period of post-ictal depression (5-10 min
      period of field response depression) following an evoked EGS. It was not
      inhibited during the tonic firing phase of the EGS. The time course for the
      recovery of the ability to induce LTP after an EGS matched the recovery of field
      responses from post-ictal depression. Moreover, the magnitude of LTP was
      inversely proportional to the duration of post-ictal depression. Delaying the
      onset of depression with the adenosine A1 receptor antagonist 8
      cyclopentyltheophylline (CPT) permitted LTP induction at a time point when it
      would normally be suppressed. Finally, the inhibitory effects of post-ictal
      depression on LTP induction were not restricted to electrically evoked EGSs, as
      LTP could not be induced during the depressed phase following a spontaneous EGS
      elicited in 10 mM K+ medium. These results demonstrate that the inhibition of LTP
      induction following epileptiform activity in vitro is in part a consequence of
      post-ictal depression of responses.

PMID- 9192186
TI  - Assessing changes over time in temporal lobectomy: outcome by scoring seizure
      frequency.
AB  - Current methods of evaluating seizure outcome after anterior temporal lobectomy
      (ATL) have major limitations. We evaluated the usefulness of a recently proposed
      system in our study of the stability of seizure frequency after ATL in 184
      patients with intractable epilepsy. Data collection by chart review was
      supplemented by an intensive program of follow-up by our survey research center
      through correspondence or phone calls according to a protocol approved by our
      Institutional Review Board. Seizure frequency during each 12-month period after
      ATL was scored for each patient. The only statistically significant change in
      seizure frequency scores during follow-up was between the third and the fourth
      years (means of 2.61 and 2.11; P < 0.045). Further assessment showed that the
      change was most likely due to an increase in the proportion of patients who
      achieved a score of 0 when they successfully stopped taking antiepileptic
      medications (9.1% in the third year and 22.5% in the fourth year; P < 0.05).
      There was no statistically significant difference between follow-up years in the
      proportion of patients achieving excellent outcome (i.e. scores of 0-4). Outcome
      remained unchanged when follow-up at each year was confined to the same patients
      throughout their postsurgical course. By using the Seizure Frequency Scoring
      System, we have demonstrated that seizure outcome remains stable after ATL. The
      scoring system facilitates the detection of subtle changes in the postoperative
      course. The advantages and the limitations of the system are discussed.

PMID- 9192187
TI  - Coupling of cortical and thalamic metabolism in experimentally induced visual and
      somatosensory focal epilepsy.
AB  - Focal epileptic activity induces widespread metabolic disturbances beyond the
      area of the electroencephalographically detectable focus. In order to find out
      whether the metabolic coupling between the epileptic focus and other brain
      regions depends on the localization of the focus, two groups of rats with
      epileptic foci at different sites were investigated. In the first group acute
      epileptic activity was induced by application of penicillin to the secondary
      visual cortex (Oc2), and in the second group to the primary somatosensory cortex
      (Par1). Metabolism was analyzed using the [14C]deoxyglucose autoradiographic
      method. In both groups of animals, hypermetabolism in the area of the focus and
      in specific functionally coupled thalamic nuclei was observed. Focal epileptic
      activity in the secondary visual cortex induced significant hypometabolism in
      remote ipsilateral cortical areas. In rats with epileptic foci in the primary
      somatosensory cortex hypometabolism in extrafocal ipsilateral cortical areas was
      less prominent. These findings provide further support for the integral
      involvement of the thalamus in modulating metabolism in remote cortical brain
      regions during focal epileptic activity. The extent of metabolic alterations may
      depend on the site of the epileptic focus and the connectivity of the recruited
      thalamic nuclei.

PMID- 9192188
TI  - Properties of interictal discharges induced by hippocampal kindling.
AB  - The present experiment was designed to reveal the characteristics of interictal
      discharges (IIDs) induced by kindling of the rabbit hippocampus. Out of 21
      animals, 13 developed stage 5 convulsions with a mean of 18 stimulations (Kindled
      (K) group), whereas the remaining eight animals did not (incomplete kindling (IK)
      group). A correlation between the duration of the afterdischarge and the
      behavioral stages was found in the K group. However, changes in frequency of
      total IIDs during kindling did not differ between the two groups. In the acute
      experiments performed after kindling, IIDs were classified into two types: simple
      and complex IIDs. The former was further classified into two subtypes (A and B)
      according to the laminar profile in the CA1 region. The A type of simple IIDs
      showed a negative polarity in the apical dendritic layer, while the B type showed
      a negative polarity in the basal dendritic layer. Complex IIDs basically
      consisted of two to three simple IIDs and were often followed by large irregular
      activity. Retrospective analysis was done, based on the classification of IIDs in
      the acute experiments (n = 12). Consequently, in the K group (n = 7), the
      frequency of complex IIDs rather than that of simple ones was closely related to
      the enhancement of behavioral responses during kindling. On the other hand, in
      the IK group (n = 5), simple IIDs occurred at a higher frequency, and did not
      parallel the changes in seizure behavior. It is concluded that complex IIDs play
      an important role in the propagation as well as the evolution of kindling
      effects.

PMID- 9192189
TI  - Chocolate--divine food, fattening junk or nutritious supplementation?

PMID- 9192190
TI  - Response rates with different distribution methods and reward, and
      reproducibility of a quantitative food frequency questionnaire.
AB  - OBJECTIVES: To evaluate the use of a self-administered quantitative food
      frequency questionnaire (QFFQ) in a national dietary survey concerning (a)
      response rates with different distribution methods and reward; (b) degree of
      underreporting of energy intake; (c) reproducibility of the QFFQ; and (d)
      seasonal variation on reported intake. DESIGN AND SUBJECTS: A pilot study was
      performed in 1992 to test response rates to the QFFQ with three different
      distribution methods, with and without reward, in a random sample of 1200 adults
      aged 16-79 y. In another study, the QFFQ was distributed to a nation-wide,
      representative random sample of 5008 adults aged 16-79 y during June, September,
      November 1993 and March 1994. Reproducibility was evaluated among 90 responders
      to the survey who answered another QFFQ six weeks later. RESULTS: The
      distribution method combining postal distribution and collecting the QFFQ by
      interviewer as well as an offer to participate in a lottery, gave the highest
      response rate (72%). The possibility to get a reward increased the response rate
      by 9, 14 and 57%, respectively, depending on the distribution method used. The
      mean daily energy intake and the percentage of subjects claiming to have unlikely
      low energy intake did not differ significantly between the different ways of
      distribution. In the main survey the mean ratio between energy intake and
      estimated basal metabolic rate was 1.58 among men and 1.47 among women, and 37%
      of men and 45% of women had a ratio below 1.35. Spearman rank correlations
      between the two QFFQ ranged from 0.48 (edible fats) to 0.91 (coffee) with a
      median coefficient of 0.70. For nutrients correlations ranged from 0.55
      (carbohydrate E%) to 0.81 (alcohol), with a median coefficient of 0.72. The
      season of questionnaire administration was of minor importance for the reported
      intake of the main foods and nutrients. CONCLUSIONS: The QFFQ-method is suitable
      for use in a Norwegian nutritional surveillance system. SPONSORSHIP: National
      Nutrition Council, Ministry for Agriculture, Ministry for Health and Social
      Affairs and Norwegian Research Council.

PMID- 9192191
TI  - Food patterns associated with intakes of fat, carbohydrate and dietary fibre in a
      cohort of Danish adults followed for six years.
AB  - OBJECTIVE: To examine associations between food consumption patterns, measured by
      a short food frequency questionnaire (FFQ), and the intakes of fat, carbohydrates
      and fibre over time, and in relation to recommended guidelines. DESIGN: The same
      329 individuals had their diet intake measured by a short FFQ and a thorough diet
      history interview, first in 1987/88, and again six years later in 1993/94.
      SETTING: The County of Copenhagen, Denmark. SUBJECTS: Three hundred and twenty
      nine men and women, aged 35-65 y selected randomly from a large population
      sample. RESULTS: At both examinations fat energy displayed the strongest positive
      associations with the intake of animal fats and negative correlations with the
      vegetables. These food items explained most of the total explained variation in
      fat intake. In general the associations between food items and intakes of
      carbohydrates and fibre were similar but inverse, to those found for fat. During
      the study period median fat energy decreased from 41-38%. A less frequent intake
      of animal fats over time predicted an increase in fat energy both among men and
      women, while a more frequent intake of fruit and pasta, and a less frequent
      intake of cakes was associated with an increase in dietary fibre. CONCLUSIONS:
      Food items like animal fats, vegetables and certain high starch foods can predict
      compliance to dietary guidelines for fat and carbohydrates. The study also shows
      that the food pattern of this Danish cohort has changed in the direction of a
      more healthy diet during the six years of follow-up. SPONSORSHIP: This study was
      granted by the Danish Agricultural and Veterinary and Danish Medical Councils and
      the Danish Health Insurance foundation.

PMID- 9192193
TI  - The use of nutritional supplements by 4-12 year olds in England and Scotland.
AB  - OBJECTIVE: To determine the levels of and factors associated with the use of
      nutritional supplements by children participating in the National Study of Health
      and Growth (NSHG). DESIGN: Cross-sectional study. SETTING: Fifty-six study areas
      in England and Scotland. SUBJECTS: Fifteen thousand, two hundred and seventy five
      children aged between 4 and 12 y. INTERVENTIONS: Parental completion of a self
      administered questionnaire on the child's health, social background and
      supplement use. Height, weight and skinfold measurements. RESULTS: An 88%
      response rate to the supplement question, 15.9% of responders reported using a
      supplement. Multivitamins were the most commonly consumed supplement (84%) with
      52% taking a supplement daily. Younger children, those whose mothers reached
      further education, whose fathers were in non-manual occupations or who lived in
      the Midlands or South were significantly more likely to use a supplement, as were
      children from smaller families or whose parents were non-smokers. There was no
      significant association between supplement use and sex, height, birthweight,
      length of gestation, father's education, number of parents in the home or
      vegetarianism. Significant differences were found in the use of supplements
      between the ethnic origin groups. Children of Afro-Caribbean, Asian or other
      origin were more likely to take a supplement compared to white English and
      Scottish groups. There were differences in the type of supplements used with Afro
      Caribbean and other origin children using more cod liver oil. CONCLUSION: We
      support the findings of other studies which show that children with the least
      need for supplements as defined by socio-economic variables are more likely to
      receive them and suggest that cultural background is also an important factor in
      influencing supplement use. SPONSORSHIP: This study was supported by grants from
      the Department of Health in England and the Scottish Home and Health Department.

PMID- 9192192
TI  - Association of alcohol consumption with HDL subpopulations defined by
      apolipoprotein A-I and apolipoprotein A-II content.
AB  - OBJECTIVE: To investigate the relationship between alcohol intake and serum level
      of high-density lipoprotein (HDL) subfractions defined on the basis of their
      apolipoprotein A-I and A-II content (LpA-I and LpA-I: A-II). DESIGN:
      Observational study. SETTING: Institute of Internal Medicine and Medical
      Physiopathology, IRCCS Maggiore Hospital, University of Milan. SUBJECTS: One
      hundred healthy males with a mean age of 42 +/- 11.1 y, selected among blood
      donors. RESULTS: Both LpA-I and LpA-I:A-II were significantly higher in men
      drinking more than 30 g a day of alcohol than in non-drinkers (LpA-I: difference
      between means 6.5 mg/dL, 95% C.I. 1.14-11.9; LpA-I:A-II difference between means
      11.5 mg/dL, 95% C.I. 0.52-22.5). The association of alcohol consumption with LpA
      I and LpA-I:A-II levels was independent from age, body mass index, physical
      activity, serum triglycerides and diet composition. CONCLUSIONS: Alcohol
      consumption is associated with an increase of serum levels of both LpA-I and LpA
      I:A-II particles and this may, at least in part, explain the reduced
      cardiovascular morbidity observed in subjects drinking moderate amounts of
      alcoholic beverages. SPONSORSHIP: Supported by grants from Ricerca Corrente
      Ospedale Maggiore di Milano IRCCS, Milan Italy.

PMID- 9192195
TI  - Effect of soluble or partly soluble dietary fibres supplementation on absorption
      and balance of calcium, magnesium, iron and zinc in healthy young men.
AB  - OBJECTIVES: This study is aimed at investigating the effect of feeding a soluble
      or partly soluble fibre rich-diet on the apparent absorption and balance of
      calcium, magnesium, iron and zinc in healthy young men, by using a chemical
      balance technique. STUDY DESIGN: Nine healthy young men were given a control diet
      or the same diet complemented with either inulin (soluble) or sugar beet fibre
      (partly soluble) during 28 d periods according to a 3 x 3 latin square design
      with three repetitions. During the 20 d adaptation period to fibre ingestion,
      experimental fibres were incorporated into bread (60%) and liquid foods (40%) up
      to a maximum of 40 g/d. Ca, Mg, Fe and Zn were measured in diets and in a 8 d
      urine and faecal composites to assess mineral absorption and balance. RESULTS:
      The dietary mineral intake provided (mg/d) 859 +/- 196 of Ca; 311 +/- 43 of Mg;
      11.6 +/- 1.7 of Fe; and 11.1 +/- 1.6 of Zn from the control diet. The apparent
      absorption of minerals from the control diet was (%) Ca: 21.3 +/- 12.5; Mg: 46.3
      +/- 10.9; Fe: 21.8 +/- 12.3 and Zn: 14.0 +/- 14.5 (mean +/- s.d.). Ingestion of
      inulin significantly increased the apparent absorption and the balance of Ca.
      Sugar beet fibre ingestion resulted in a significant increase in Ca intake and
      balance, without modification its apparent absorption. Apparent absorption and
      balance of Mg, Fe and Zn were not significantly altered by the ingestion of
      either experimental fibre. CONCLUSIONS: Addition of the two experimental fibres
      (inulin or sugar beet fibre) to normal mixed diets can improve Ca balance without
      adverse effects on other mineral retention. SPONSORSHIP: This project was
      supported by the French Ministry of Agriculture, Fisheries and Foods (programme
      Aliment #2002-Aliment Demain; No. 906335). The authors acknowledge the societe
      Agro Industries, Recherche et Developpement (Mr R. De Baynast) who supplied them
      with the experimental fibres.

PMID- 9192194
TI  - Energy expenditure and substrates oxidative patterns, after glucose, fat or mixed
      load in normal weight subjects.
AB  - OBJECTIVES: To evaluate energy balance after three isocaloric oral loads of
      different composition and to establish possible relationships between the
      substrates oxidative patterns and the modifications of insulin and free fatty
      acids (FFA) plasma profiles. DESIGN: Each subject received, in a randomized
      order, three oral loads of 2658 +/- 45 kJ (636 +/- 11 Kcal) either as glucose,
      lipids (cream) or a mixture (glucose+cream). SETTING: The experiments were
      performed at the University Hospital of Geneva. SUBJECTS: Ten normal body-weight
      volunteers. METHODS: Energy expenditure (EE) and substrates oxidation were
      measured by indirect calorimetry during 8 h following each load. Plasma glucose,
      insulin and FFA were also measured. RESULTS: EE was 1776 +/- 107, 1818 +/- 125
      and 1785 +/- 117 KJ over 8 h after glucose, mixed and lipids load, respectively.
      Glucose oxidation was the highest after oral glucose as compared to mixed and
      lipids load, while the highest value of lipids oxidation was measured after fat
      load. A significant relationship linked fat oxidation to plasma FFA (r = 0.54, P
      < 0.002) as well as to insulin (r = -0.40, P < 0.002). CONCLUSIONS: (a) The
      energetic cost of glucose and fat intake is the same; (2) after each load, the
      main source of energy corresponds to the substrate administered; (3) both plasma
      insulin and FFA influence the substrate oxidative patterns observed after each
      load; (4) alimentary fat may contribute to fat oxidation by maintaining elevated
      plasma FFA levels.

PMID- 9192196
TI  - Weekly iron supplementation is as effective as 5 day per week iron
      supplementation in Bolivian school children living at high altitude.
AB  - OBJECTIVE: To compare the efficacy of a daily and a weekly iron supplementation
      on the hematological status of anemic children living at high altitude. DESIGN:
      Double blind iron supplementation trial including a placebo control group.
      SETTING: A socioeconomically disadvantaged district of La Paz, Bolivia (altitude
      of 4000 m). SUBJECTS: Anemic (hemoglobin concentration < or = 144 g/L), 3.3-8.3 y
      old children of both sexes. INTERVENTION: Children received a placebo (n = 57) or
      a dose of 3-4 mg of elemental iron per kg body weight (FeSO4 tablets) 1 d per
      week (n = 58) or 5 d per week (n = 58) for 16 weeks. RESULTS: Hemoglobin and zinc
      erythrocyte protoporphyrin concentrations improved significantly in supplemented
      groups but not in the placebo group. Changes in hemoglobin during the study were
      not significantly different between supplemented groups (weekly group: 15.2 +/-
      6.9 g/L and daily group: 18.6 +/- 11.1 g/L) but were different from the placebo
      group (0.5 +/- 7.1 g/L, P < 0.001). At the end of the supplementation period, the
      hemoglobin distribution was Gaussian, and similar in both supplemented groups.
      Adjusting for the initial hemoglobin concentration, final hemoglobin and its
      changes were similar in both supplemented groups. CONCLUSION: Weekly iron
      supplementation is as efficacious as daily iron supplementation in improving iron
      status and correcting moderate iron deficiency anemia in Bolivian school children
      living at high altitude. SPONSORSHIP: Program supported in part by ORSTROM, the
      French Ministry of Foreign Affairs and the National Secretary's Office of Health,
      Bolivia.

PMID- 9192197
TI  - The association between dietary patterns and cardio vascular disease risk
      indicators in healthy youngsters: results covering fifteen years of longitudinal
      development.
AB  - OBJECTIVE: To examine longitudinal relationships between nutrition and risk
      indicators for cardio vascular diseases (CVD) during adolescence and young
      adulthood. DESIGN: A longitudinal study over fifteen years. SUBJECTS: 98 females
      and 84 males, from 13 to 27 years. METHODS: By means of six interviews dietary
      patterns were determined. Blood samples were analyzed for serum concentration of
      total cholesterol (TC), and high-density-lipoprotein (HDL), blood pressure, body
      fat and maximal aerobic power (VO2max) were determined. The longitudinal
      relations were analyzed with generalized estimation equations (GEE), a
      statistical technique in which relations at different time-points are tested
      simultaneously. RESULTS: Compared to Dutch recommendations six out of seven macro
      nutrients appear to be unfavorable with respect to CVD. Borderline or high CVD
      risk values are apparent at 27 y in more than 25% of the subjects with respect to
      percentage body fat and serum total cholesterol in both sexes. In males 40% or
      more show borderline hypertension. The 'univariate' longitudinal analyses showed
      significantly positive relations: (1) between the intake of animal protein,
      saturated fat (SFA), cholesterol (Cho1) and TC, and HDL; (2) between total energy
      intake (EN) and systolic blood pressure, and VO2max. Significantly negative
      associations were found: (1) between EN, poly-unsaturated fat (PUFA) and TC
      concentrations; (2) between EN and sum of four skinfolds (SSF). CONCLUSIONS: With
      increasing age, over a period of 15 y in both sexes the SFA and Cho1 intake
      relate significantly to the development of a negative CVD risk profile. The
      intake of PUFA relates positive to a CVD risk profile. The significantly negative
      relation between EN intake and body fat (SSF) is partly explained by the relation
      between EN and VO2max.

PMID- 9192198
TI  - The effect of dietary sodium on calcium metabolism in premenopausal and
      postmenopausal women.
AB  - OBJECTIVE: To investigate the effects of high and low sodium diets on urinary
      calcium, bone turnover and calcium absorption in pre and postmenopausal women.
      DESIGN: Experimental, prospective and longitudinal study. SETTING: Samples were
      taken at the hospital and the diets were followed at home. SUBJECTS: Volunteers
      were recruited from the hospital and were either hospital staff or post-graduate
      students. No volunteers failed to complete the study but one was omitted from
      analysis due to lack of compliance. INTERVENTIONS: Eleven healthy premenopausal
      women aged 22-47 y and 11 healthy postmenopausal women ages 45-70 y followed a
      high (300 mmol/d) and a low (50 mmol/d) sodium diet for one week each. On the 7th
      day of each diet, blood and urine samples were taken. RESULTS: On the high sodium
      diet 24 h urinary sodium and calcium values relative to creatinine were
      significantly higher for all subjects (P < 0.05). Postmenopausal women on the
      high sodium diet had biochemical evidence of increased bone resorption in
      relation to the low sodium diet. However in premenopausal women there was no such
      change. Calcium absorption did not change significantly in either group.
      CONCLUSIONS: It appears that postmenopausal, but not premenopausal, women respond
      to a high sodium diet by an increase in bone resorption which may lead to reduced
      bone density. SPONSORSHIP: Arthritis and Rheumatism Council Project Grant R44.

PMID- 9192199
TI  - Selenium status of a group of Scottish adults.
AB  - OBJECTIVE: To examine dietary selenium intake and indices of selenium status
      (plasma and red blood cell selenium and glutathione peroxidase activities) in
      apparently healthy Scottish individuals. DESIGN AND SUBJECTS: One hundred
      subjects, aged between 40 and 60 y, completed a seven day weighed food intake and
      provided blood samples for selenium status analysis. SETTING: Inverurie,
      Aberdeenshire, Scotland. RESULTS: Average reported selenium intake was low (43
      micrograms/d). A significant number of subjects had reported intakes below the
      RNI. Low levels of plasma selenium were also found but no subject had values
      below 40 micrograms/1. Red blood cell selenium was within the reference range
      established for a healthy UK population. Smoking status had no consistent effect
      on selenium status. CONCLUSIONS: The results of the present study suggest that
      selenium status of certain Scottish individuals may be compromised and that
      further studies are warranted. SPONSORSHIP: BASF, Germany; The Tobacco Products
      Research Trust, UK; Scottish Office Agriculture Environment and Fisheries
      Department.

PMID- 9192201
TI  - Reproductive toxicity testing of pharmaceutical compounds to support the
      inclusion of women in clinical trials.
AB  - 1. The potential for toxicity to reproduction and the developing fetus is an
      important concern requiring attention during the development of new medicines.
      However, there are differences in the opinions of the regulatory authorities in
      Europe, Japan and the USA regarding the nature and amount of data from
      reproductive toxicity tests that should be available at the various stages of
      clinical development. 2. Forty-one companies or their subsidiaries from Europe,
      Japan and the USA provided data for a questionnaire-based study, carried out in
      1994, to ascertain the practices of pharmaceutical companies and their views on
      an ideal approach to the timing of reproduction and development toxicity studies
      in relation to clinical investigation. 3. Differences were identified in the
      stage of drug development at which animal studies were completed, the sequence of
      completion of specific studies, and the extent of reproduction testing completed
      to support the inclusion of women in clinical trials. 4. A harmonised, but
      flexible, guidelines, encompassing the timing of reproductive toxicity studies in
      relation to clinical trials, would permit better integration between clinical and
      non-clinical studies in an international drug development programme.

PMID- 9192200
TI  - Validation of dietary intakes of protein and energy against 24 hour urinary N and
      DLW energy expenditure in middle-aged women, retired men and post-obese subjects:
      comparisons with validation against presumed energy requirements.
AB  - OBJECTIVES: To compare validation of reported dietary intakes from weighed
      records against urinary nitrogen excretion and energy expenditure measured by
      DLW, and to examine the utility of the Goldberg cut-off for EI:BMR in the
      identification of under-reporters. DESIGN: Energy (EI) and nitrogen (protein)
      intake (NI) were measured by 16 d of weighed diet records collected over 1 y.
      They were validated against urinary nitrogen excretion in 5-8 (mean 6.0) 24 h
      urine collections and total energy expenditure (EE) measured by doubly labelled
      water (DLW). Basal metabolic rate (BMR) as measured by whole body calorimetry in
      women or bedside ventilated hood (Deltatrac) in men. Individual subjects were
      identified as under-reporters if Urine N:NI was > 1.00 or if EI:EE was < 0.79.
      The agreement between the two ratios in detecting under-reporting was examined.
      The results from the direct validation by DLW were also compared with validation
      using the Goldberg cut-off for EI:BMR (Goldberg et al, 1991). SUBJECTS: Eighteen
      women aged 50-65 y and 27 men aged 55-87 y were selected from participants in two
      larger dietary surveys as representing the full range of dietary reporting as
      measured by Urine N:NI. Data from a previous study of 11 post-obese subjects were
      also included. RESULTS: The two ratios, Urine N:NI and EI:EE, were significantly
      related (r = -0.48, P < 0.01). Using the above cut-offs, seven (4F, 3M) subjects
      were identified as under-reporters by both methods, one (1M) by Urine N:NI only
      and 8 (3F, 5M) by EI:EE only. There was close agreement in post-obese subjects
      where 6 subjects showed a substantial degree of under-reporting by both methods
      (r = -0.87, P < 0.001). The correlation between direct validation by DLW and
      EI:BMRest was 0.65 (P < 0.001). Some limitations of the Goldberg cut-off for
      identifying individual under-reporters were demonstrated. CONCLUSIONS: EI:EE
      provides an estimate of the degree of under-reporting of energy at the group and
      individual level. Urine N:NI identifies under-reporting of protein intake and the
      most obvious under-reporters of energy, but is probably of lesser value in
      estimating the overall degree of under-reporting of energy at group level. Good
      validation by EI:BMR depends on knowledge of physical activity at both group and
      individual level. However, the correlation of 0.65 between EI:EE and EI:BMRest
      suggests that EI:BMR could be usefully incorporated into analysis of data from
      epidemiological studies. Validation measures consisting of at least predicted
      EI:BMR ratios and urinary measures should be incorporated into dietary surveys.
      SPONSORSHIP: This work was funded by the Ministry of Agriculture Fisheries and
      Food, the Medical Research Council, the Cancer Research Council and the Swedish
      Medical Research Council and the Henning and Johan Throne-Holst Foundation.

PMID- 9192202
TI  - Presence of methenamine/glutathione mixtures reduces the cytotoxic effect of
      sulphur mustard on cultured SVK-14 human keratinocytes in vitro.
AB  - The basal epidermal keratinocytes of the skin are a main target for the
      vesicating agent, sulphur mustard (SM). A human keratinocyte cell line (SVK-14)
      has been used to model the effects of SM on the basal epidermal keratinocytes and
      subsequently to test the efficacy of potential prophylactic compounds in reducing
      the SM-induced cytotoxicity. The cultures were pretreated with mixtures of
      methenamine (HMT) and glutathione (GSH) for 1 h prior to exposure to 10 microM
      SM. The viability of the cultures was then assessed using neutral red (NR) dye
      uptake and crystal violet DNA staining assays at 24 h intervals post exposure.
      Pretreatment led to a 1.9 fold increase in culture viability (NR assay) compared
      to those exposed to SM only, and a 2.3 fold increase in cell number (crystal
      violet assay). Photomicrography showed that pretreatment preserved the morphology
      of the cultured cells and maintained their mitotic activity whereas those exposed
      to SM only show non-proliterative cultures with extensive cellular damage. The
      results of this study show that it is possible to protect mitotically active
      cultures from the effects of SM, however the measures must be in place prior to
      SM exposure.

PMID- 9192203
TI  - Reactive oxygen species involvement in ricin-induced thyroid toxicity in rat.
AB  - Ricin is known to have diverse effects on the cells of different organs like
      liver, kidney, pancreas, intestines and parathyroid. Acute decrease in serum
      thyroid hormone level 24 h after ricin administration (1.5 micrograms/100 g) led
      us to suspect the toxic action of ricin on the thyroid. We monitored the lipid
      peroxidation (LP) and anti-oxidant status of the thyroid tissue to determine the
      role, if any, played by reactive oxygen species (ROS) in this pathology. An
      increase of 39% in LP and 47% in superoxide dismutase, along with a 8.5% decrease
      in catalase points to the imbalance in the antioxidant defence involving hydrogen
      peroxide and its univalent reduction product, the hydroxyl radical. Thyroid
      histopathology shows destruction of thyroid follicles and necrosis, which may be
      due to ROS and may partly explain the 50% reduction in circulating thyroid
      hormones seen after ricin administration.

PMID- 9192205
TI  - Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2
      propanol and selectively inhibits CYP2E1 activity in the rat.
AB  - The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome
      P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity
      in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively
      inhibited enzyme markers for CYP2E1 activity, and provided substantial protection
      against DCP hepatotoxicity. At a higher dose (25 mg/kg), DEDC also inhibited an
      enzyme marker for CYP1A2 activity and provided complete protection against DCP
      hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a
      selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is
      mediated principally by CYP2E1, with a possible contribution from CYP1A2.

PMID- 9192204
TI  - Pro- and anti-oxidant parameters in rat liver after short-term exposure to
      hexachlorobenzene.
AB  - The association between an in vivo oxidative stress condition of the liver and
      hepatic porphyria during HCB intoxication is postulated. After 30 days of
      treatment, HCB (25 mg/kg b.w.) promotes an induction of microsomal cytochrome
      P450 system, increase in microsomal superoxide anion generation accompanied by
      increased levels of liver lipid peroxidation, as measured by the production of
      thiobarbituric acid reactants and by spontaneous visible chemiluminescence.
      Concomitantly, liver antioxidant defenses are slightly modified, with decreased
      activity of glutathione peroxidase, superoxide dismutase and glucose-6-phosphate
      dehydrogenase contributing to an oxidative stress condition of the liver. These
      liver biochemical alterations are closely related to increased levels of urinary
      coproporphyrin, plasma AST and ALT activities and to the onset of liver
      morphological lesions.

PMID- 9192206
TI  - In utero and lactational exposure of carbofuran to rats: effect on testes and
      sperm.
AB  - Male offspring of adult females treated with 0.2 or 0.4 mg/kg during either the
      whole of pregnancy or the whole of the lactation period did not induce
      generalised toxic effects. A significant alteration in enzymatic activities i.e.
      SDH (decreased), LDH and Y-GT (increased) were observed in testes only at 0.4
      mg/kg. A decrease in sperm motility, sperm count along with increase in percent
      abnormal sperm was observed at 0.4 mg/kg dose level. Histopathological
      examination revealed loss of spermato-genesis, degenerative changes in Sertoli
      cells which are well supported with biochemical studies indicating that
      carbofuran interferes with the maturation process of testis. No such effects were
      observed at 0.2 mg/kg. The testicular and spermatotoxic effects observed in rats
      given in utero or lactational exposure may be due to transfer of carbofuran or
      its metabolites through placenta or mothers milk.

PMID- 9192208
TI  - Acute hydrogen selenide gas poisoning admissions in one of the hospitals in
      Delhi, India: case report.
AB  - Acute gas poisoning is one of the most important medicosocial problems in the
      developing countries. An outbreak of acute inhalation exposure to hydrogen
      selenide occurred in Delhi, India. This report includes our findings on
      epidemiological, clinical and biochemical investigations in 31 cases hospitalized
      immediately after the gas poisoning.

PMID- 9192207
TI  - Ocular injury with xylene--a report of two cases.
AB  - Xylene is a hydrocarbon solvent found in various industrial preparations such as
      paint and is widely used in pathology laboratories. When inadvertently instilled
      into the eye significant ocular injury can occur with the potential for
      blindness. Such injuries to the ocular surface resemble those due to alkali.
      Ocular surface injury due to xylene has not been reported previously in the
      literature. We strongly recommend that these injuries be treated as emergencies
      in a similar way to alkali burns in the Eye department since the chemical mixture
      of which xylene forms a part may be alkaline. Such an approach is vital in order
      to save sight.

PMID- 9192209
TI  - Intravenous organophosphate injection: an unusual way of intoxication.
AB  - Organophosphate insecticides strongly inhibit both true cholinesterase and
      pseudocholinesterase activities. In this report, we have reported a patient who
      injected himself a strong organophosphate compound, methamidophos, and showed the
      typical clinical picture of organophosphate intoxication. As far as we know, this
      is the first case of intoxication by intravenous (i.v.) injection. With the
      appropriate therapy, his symptoms disappeared in a few days.

PMID- 9192210
TI  - Lead exposure in papier mache workers.
AB  - Lead exposure was assessed in a random cohort of 70 male papier mache workers and
      compared with 35 age and sex matched controls. Blood-lead levels in workers were
      significantly higher than in controls (Mean 68.07 +/- 44.64 ug/dl vs 25.52 +/-
      16.56 ug/dl respectively; P < 0.001). Urinary lead was also higher in workers
      (128.53 +/- 52.61 ug/l) compared to controls (91.18 +/- 27.06, P < 0.001), but
      excretion of urinary coproporphyrin in the two groups was not significantly
      different (102.78 +/- 153.42 vs 70.03 +/- 27.06 ug/l, P > 0.05). Blood levels
      bore a significant correlation with age but did not bear any correlation with the
      duration of exposure. Various modes of exposure to lead included hand mixing of
      paints, skin application of the paint to match shades and making point of the
      brush using lips and the tongue.

PMID- 9192211
TI  - Changes in immunoglobulin concentrations and urinary 2,5-hexanedione
      concentrations.

PMID- 9192212
TI  - Occupational medicine in Chile.

PMID- 9192214
TI  - Risk of spontaneous abortion and maternal exposure to organic solvents in the
      shoe industry.
AB  - OBJECT: A high risk of spontaneous abortion was observed in women exposed to
      organic solvents during pregnancy. Since this risk was not found in the shoe
      industry, where these solvents are widely used, we carried out a case-control
      study on the risk of spontaneous abortion in a health district (Veneto, Northern
      Italy) where about 8,000 people work in shoe manufacturing. Aliphatic
      hydrocarbons were generally used; their concentrations were repeatedly below the
      mixture TLVs in the observation period. METHODS: Cases (clinically recognized
      spontaneous abortion, ICD codes 632-634-636) and age-/year-/residence-matched
      controls (admitted for normal delivery) were traced in the files of the regional
      hospital discharges register. Data on 108 cases (81% response) and the same
      number of reference subjects were collected on questionnaires completed by nurses
      trained in occupational medicine. There were questions on confounding and
      occupational factors, and an open question to ensure a complete description of
      work done during pregnancy. An occupational physician, working blind, then coded
      exposure to organic solvents according to a three-level polytomous variable (no,
      low, high exposure). RESULTS: The cases/controls not exposed, exposed to low
      levels and exposed to high levels of organic solvents were 78/88, 12/12, and 18/8
      respectively. Adjusted for the confounding factors, the relative risk (RR) of
      spontaneous abortion for high exposure to organic solvents during pregnancy was
      3.85, with 95% confidence intervals (CI) ranging from 1.24 to 11.9. RR was 1.58
      (CI = 0.62-4.06) in women exposed to low solvent concentrations. CONCLUSIONS: Our
      results support the hypothesis that spontaneous abortion may be an adverse effect
      of exposure to high levels of organic aliphatic solvents in women employed in
      shoe manufacture.

PMID- 9192213
TI  - Changes in natural killer cell subpopulations in lead workers.
AB  - To investigate the effects of lead on human immune system, we analyzed T cell
      subpopulations (CD4+, CD8+ and CD3+ cells), natural killer (NK) cell
      subpopulations (CD16+ and CD57+ cells) and B (CD19+) cells in peripheral blood in
      29 male lead workers. All were engaged in manufacturing lead stearate in a
      chemical factory. They were aged 23-74 (mean 49) years. Their blood lead
      concentrations (PbB) were between 7 and 35 (mean 18) micrograms/dl. They were
      divided into two groups according to their PbB: a high-PbB group (> or = 20
      micrograms/dl), and a low-PbB group (< 20 micrograms/dl). The control group
      consisted of 19 "healthy" male workers without a history of occupational exposure
      to lead or to other hazardous substances, aged 48-67 (mean 58) years. The number
      and percentage of CD16+ cells in the high-PbB group were significantly lower than
      those in the controls and in the low-PbB group. There was significant negative
      correlation between the number of CD16+ cells and PbB in the lead workers. The
      percentage of CD8+ cells in the high-PbB group was larger than that in the
      controls and in the low-PbB group. It is suggested that the CD16+ NK cell should
      be a major site of the effects of lead on lymphocyte subpopulations.

PMID- 9192215
TI  - Frequency of patients with acute asthma in relation to ozone, nitrogen dioxide,
      other pollutants of ambient air and meteorological observations.
AB  - OBJECTIVE: To study the association of the daily frequency of registration of
      patients with acute asthma at the emergency department of a central hospital in
      the south-west of Sweden with levels of air pollution and meteorological
      observations. METHODS: A retrospective longitudinal study was made of asthma
      patients taken from a hospital registry. This information was correlated with
      measurements of ozone, nitrogen dioxide, sulphur dioxide, toluene, temperature
      and relative humidity. Patients were from the catchment area of the Central
      Hospital of Halmstad containing around 120,000 inhabitants. A total of 4127
      visits of patients with acute asthma to the emergency department at the Central
      Hospital of Halmstad were registered during a period of 1247 days from January
      1990 to May 1993. The differential optical absorption spectroscopy (DOAS)
      technique was used to monitor levels of air pollutants over a distance of 1000 m
      in the central part of the town of Halmstad. Data on temperature, relative
      humidity, precipitation, wind speed and wind direction for the time period were
      supplied by the Swedish Meteorological and Hydrological Institute (SMHI).
      RESULTS: There were many statistically significant correlations between the
      levels of air pollutants and the meteorological measurements and a strong
      negative correlation between ozone and nitrogen dioxide. There was a
      statistically significant effect on asthma visits in children of low temperature
      and high nitrogen dioxide levels, and on asthma visits in adults of high
      temperature and high levels of ozone. CONCLUSIONS: There was a different reaction
      pattern in children and adults with asthma regarding temperature and
      ozone/nitrogen dioxide. The strong correlations between temperature and air
      pollution and between the levels of ozone and nitrogen dioxide made the true
      relation between asthma, air pollution and temperature hard to evaluate
      statistically.

PMID- 9192216
TI  - Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode
      producing plant: biological monitoring of 1-hydroxypyrene and monohydroxylated
      metabolites of phenanthrene.
AB  - OBJECTIVE: The objective of this study was to assess external and internal
      exposure to polycyclic aromatic hydrocarbons (PAHs) of workers who are employed
      in a graphite-electrode producing plant. Additionally we wanted to contribute to
      the question of biological limit values in order to reduce exposure to tolerable
      levels. METHODS: At five different working places 12 stationary and 16 personal
      air measurements were carried out to determine the concentrations of
      phenanthrene, fluoranthene, pyrene, benz[a]anthracene, chrysene,
      benzo[b]fluoranthene, benzo[a]pyrene and dibenz[a, h]anthracene in air. In
      addition, we investigated the excretion of 1-, 2 + 9-, 3- and 4
      hydroxyphenanthrene and of 1-hydroxypyrene in the urine of 67 workers by a very
      sensitive and practical high-performance liquid chromatographic (HPLC) method
      with fluorescence detection; 2- and 9-hydroxyphenanthrene could not be separated
      with our analytical method. RESULTS: During the production of graphite electrodes
      significantly higher PAH exposures were found in the baking and impregnation area
      than in the crushing, graphitisation and conditioning area. The results of
      personal air measurements (mean values of the sum of eight PAHs) are: 29.3
      (baking), 23.4 (impregnation), 5.2 (crushing), 1.3 (graphitisation) and 0.4
      microgram/m3 (conditioning). Stationary air measurements yielded similar
      concentrations. Workers employed in the baking and impregnation areas excreted
      the highest amount of PAH metabolites in urine. The 1-hydroxypyrene
      concentrations (median) were: 23.4 (baking), 22.0 (impregnation), 9.6 (crushing),
      1.8 (graphitisation) and 2.3 micrograms/g creatinine (conditioning). The
      corresponding concentrations of the sum of monohydroxylated phenanthrene
      metabolites (median) were: 23.1, 36.0, 10.4, 4.6 and 7.6 micrograms/g creatinine.
      Within the monohydroxylated phenanthrene metabolites 3-hydroxyphenanthrene
      predominates with a percentage of 43%. Our results showed that a benzo[a]pyrene
      concentration in air of 2 micrograms/m3 would lead to 1-hydroxypyrene
      concentrations in urine of 20-74 micrograms/g creatinine. That means that
      corresponding values in the literature which lie between 4.4 and 6.2 micrograms/g
      creatinine are due to other conditions of exposure and cannot be applied to
      graphite-electrode producing plants. CONCLUSIONS: Although to date there are no
      obligatory biological exposure limits for metabolites of PAHs in urine, it must
      be concluded that the internal PAH exposure is too high at some work places in
      this plant, as is generally the case in graphite-electrode producing plants. This
      is probably caused by skin absorption of PAHs. So for the prevention of health
      hazards by PAH, internal exposure must be measured using biological monitoring.
      Although it has not been possible to establish biological exposure limits for
      PAHs until now, we suggest a reduction in skin contact with these substances and
      thereafter use of the 90th percentile of the results of biological monitoring as
      "action levels" for corrective measures.

PMID- 9192217
TI  - Neurotoxicity of long-term low-level exposure to carbon disulphide: results of
      questionnaire, clinical neurological examination and neuropsychological testing.
AB  - OBJECTIVE: Carbon disulphide (CS2) is highly neurotoxic. There is ample evidence
      of damage to the peripheral and central nervous system. The air concentration at
      which such adverse effects can first be observed is presently a subject of
      controversy. METHODS: In a cross-sectional study of CS2-exposed workers from the
      viscose industry and healthy controls, data on neurological complaints, basic
      laboratory diagnosis, clinical neurological examination and neuropsychological
      testing were evaluated. Data were from 222 workers in the viscose industry
      exposed to CS2 and 191 employees from the same factory with similar physical and
      psychological stress factors but without occupational contact with neurotoxic
      substances. Multiple linear or multiple logistic regression analysis was used to
      check for statistical differences. RESULTS: The median of the CS2-measurements
      using personal air sampling was below the current maximum concentration
      permissible (MAK value) in Germany (10 ppm) in all departments. The threshold
      limit value was, however, exceeded in almost 10% of the persons investigated.
      Exposure fluctuated between < 0.2 and 65.7 ppm (median of all departments was
      4.02 ppm). As a parameter of internal exposure, CS2-metabolite 2-thio-1,3
      thiazolidine-4-carboxylic acid (TTCA) concentrations in the urine of the exposed
      persons were between < 0.16 and 10.9 mg/g creatinine (median 1.43 mg/g).
      CONCLUSIONS: Neither an increase in subjective complaints nor an increase in
      pathological findings in clinical-neurological and neuropsychological examination
      could be found in persons exposed to CS2 at the exposure levels described.

PMID- 9192218
TI  - Allergic disease, immunoglobulins, exposure to mercury and dental amalgam in
      Swedish adolescents.
AB  - High-dose exposure to inorganic mercury in man can influence the immune system
      and in rare cases cause immune-related disease. Some experimental animals also
      react with autoimmunity after low doses of inorganic mercury. Glomerulonephritis
      and an increased formation of immunoglobulin type E (IgE) are characteristic of
      these reactions. A recent study of 15-year-old adolescents demonstrated an
      association between immunoglobulin type A (IgA) and mercury concentration in
      plasma (P-Hg). There was also an association between allergic disease and IgA
      levels. The present study included 54 male and 23 female 19-year-old students who
      were recruited from a cohort that had been previously defined in a survey of
      allergic disease. Of the students, 39 (51%) had asthma, allergic
      rhinoconjunctivitis or eczema. Similar amalgam burden and P-Hg levels were
      observed in students with (n = 39) and without (n = 38) allergic disease (P =
      0.48 and P = 0.98, respectively). As expected, IgE levels were significantly
      higher in the group with allergic disease (P = 0.006), but there was no
      association between P-Hg and IgE. The P-Hg levels were very low (median 1.50
      nmol/l) and correlated significantly (r = 0.31) with the small number of amalgam
      surfaces (P = 0.007). Thirty-seven students had no amalgam fillings. P-Hg levels
      did not associate significantly with IgA, but did so with IgG2 (r = 0.33; P =
      0.003). No conclusive correlation was observed between IgG2 and amalgam fillings.
      The findings of this study in 19-year-old subjects differ from earlier data
      obtained in a sample 4 years younger. The possibility of chance in the
      association between P-Hg levels and IgG2 must, however, be considered.

PMID- 9192220
TI  - Pulmonary function and symptoms of welders.
AB  - OBJECTIVE: As the findings on changes in pulmonary function of welders have been
      inconsistent, this study aimed to analyze respiratory symptoms and pulmonary
      function among welders and controls with particular emphasis on small airways
      dysfunction. METHODS: Cross-sectional analysis, using spirometry and a
      standardized questionnaire, was used to evaluate 521 participants, 166 of whom
      (64 welders and 102 controls) were evaluated for pulmonary symptoms, occupational
      inhalative exposures, leisure time activities, and anamnestic data. RESULTS: The
      welders reported more pulmonary symptoms than the controls. They exhibited a
      decreased mean expiratory flow (MEF) at 25% and 50% of vital capacity (MEF25,
      MEF50) while the other parameters tested (forced vital capacity, forced
      expiratory volume in 1 s) were unchanged compared with the controls. Multivariate
      regression analysis revealed that smoking explained the observed variance; only
      in MEF25 the duration of welding exposure had a significant influence on this
      parameter. CONCLUSIONS: The significantly reduced flow values among the welders
      compared with the controls indicates the presence of small airways disease.
      Differences in smoking habits accounted for more than double the differences in
      MEF25 than did chronic welding fume exposure, confirming the role of the former
      as the main risk factor leading to the decline in lung function. Longitudinal
      studies are needed to evaluate the long-term effects of chronic welding fume
      exposure, in particular with a view to identifying especially susceptible
      workers.

PMID- 9192219
TI  - Ethnic differences in biological monitoring of several organic solvents. I. Human
      exposure experiment.
AB  - OBJECTIVES: In order to improve the reliability of biological monitoring and the
      development of biological limit values, ethnic differences for several organic
      solvents were studied in Orientals and Caucasians. METHODS: Six Caucasian and six
      Oriental volunteers were exposed to each organic solvent in an exposure chamber
      for 6 h. Exposure concentration to each organic solvent studied was 50 ppm for
      perchloroethylene, 50 ppm for styrene and 100 ppm for m-xylene, respectively.
      Biological monitoring was carried out for the parent organic solvents in exhaled
      air and in blood, and for the metabolites in urine during and after exposure.
      RESULTS: Caucasians showed higher concentrations of perchloroethylene in exhaled
      air than Orientals after exposure. But Caucasians showed lower concentrations of
      styrene in the exhaled air than Orientals during the second half of exposure and
      after it. Orientals showed lower concentrations of urinary metabolites than
      Caucasians except for mandelic acid. There were no statistically significant
      differences in the concentrations of solvent in blood for all three solvents.
      CONCLUSIONS: Implications of these differences in biological levels, under
      identical exposure conditions, are discussed in the context of biological
      monitoring.

PMID- 9192221
TI  - Do weekly and fast-rotating shiftwork schedules differentially affect duration
      and quality of sleep?
AB  - Characteristics of shiftwork schedules can have distinct impacts on workers'
      sleep. This report presents comparisons of the effects of two different shiftwork
      schedules on duration and quality of the main sleep episodes in comparable worker
      populations at two different petrochemical plants. No significant differences
      were found for sleep duration in comparing the two plants. However, within each
      plant's shift cycles, morning and night shifts showed shorter sleep durations
      than all other workdays and days off. Quality of sleep was perceived as lowest
      for night shifts of both plant schedules, and of lesser quality for weekly than
      for fast-rotating shifts. These results support recommendations for reducing the
      number of consecutive nights of shiftwork. However, before recommending any
      optimal shift schedule, interactions of sleep duration and quality with shift
      schedules need much further evaluation.

PMID- 9192222
TI  - Korean analytical quality assurance (KAQUA) program for biological monitoring.
AB  - The Korean analytical quality assurance (KAQUA) program on biological monitoring
      was performed by the Industrial Health Research Institute in Korea in spring,
      1995. The object of the KAQUA program is to improve the analysis capability for
      the biological monitoring of hazardous chemicals and to confirm the reliability
      of data from each laboratory. The items chosen for the first round were analyses
      of lead in blood (PbB) and of hippuric acid in urine (HAU). Eighty-eight
      laboratories in Korea participated in this program. Two levels of samples,
      randomly chosen among six levels for each item, were sent to the participants.
      The consensus value from participants and reference laboratories was determined
      by statistical analysis and used as a reference value. The tolerance range was +/
      15% (+/-6 micrograms/dl for PbB below 40 micrograms/dl) of the reference value.
      The mean proficiency rate of analytical data increased dramatically in the first
      round compared with a pre-round that was provided as part of a training course
      for participants before performing the first round. The mean proficiency rate of
      PbB was 69% at pre-round and increased at 91% at the first round; for HAU the
      increase was from 58% to 88%. Not only the analytical results but also raw data
      were reviewed to find problems which might have arisen during the analytical
      process. Re-education courses provided after final evaluation of each participant
      by means of telephone discussion, correspondence course, and experimental
      practice, were helpful in achieving the purpose of the analytical quality
      assurance program.

PMID- 9192223
TI  - Hyperviscosity and microproteinuria in central obesity: relevance to
      cardiovascular risk.
AB  - OBJECTIVES: To investigate the role of blood rheology changes in the occurrence
      of glomerular proteinuria in obese patients with central fat distribution.
      SUBJECTS: Fifty-nine obese out-patients (31 with central and 28 with peripheral
      body fat distribution) and 24 healthy subjects. MEASUREMENTS: Blood and plasma
      viscosity (Rotational viscometer CV100 HAAKE), erythrocyte deformability (whole
      blood filtration time), fibrinogen (nephelometry), urinary excretion rates of
      albumin, IgG, transferrin and IgA (nephelometry). RESULTS: Higher blood viscosity
      (at low and high shear-rates), plasma viscosity, fibrinogen, erythrocyte
      aggregability and lower erythrocyte deformability were found in patients with
      central obesity than in patients with peripheral obesity (P < 0.01) and in
      healthy subjects (P < 0.001). Furthermore an increased urinary excretion rate of
      albumin (P < 0.001), IgG (P < 0.001), transferrin (P < 0.01) and IgA (P < 0.05)
      was found in patients with central obesity than in the other two groups. Blood
      hyperviscosity (at shear-rate 1 s-1 and 1/200 ratio) significantly correlated
      with the amount of urinary excretion of proteins independently of the other
      clinical and metabolic variables. CONCLUSIONS: The data demonstrated
      haemorheologic disorders related to pathologic proteinuria in patients with
      central obesity. The interaction between these two components may increase the
      risk of widespread cardiovascular disease.

PMID- 9192224
TI  - Body mass index and all-cause mortality among people age 70 and over: the
      Longitudinal Study of Aging.
AB  - OBJECTIVES: To assess the relationship between body mass index (BMI; kg/m2) and
      mortality in a large nationally representative sample of US adults over age 70
      years. DESIGN: Prospective longitudinal cohort study, the Longitudinal Study of
      Aging (LSOA). Subjects were all those 7260 black and white people (2769 men, 4491
      women) initially interviewed in 1984 for whom height and weight were available.
      These subjects were followed through to 1990. MEASUREMENTS: Measurements included
      self-reported height and weight, date of death if subjects died, sex, age, race,
      measures of socio-economic status, number of living first degree relatives, and
      responses to questions asking whether the subject had retired due to poor health,
      had difficulty eating, worried about their health, and felt their health was
      worse than during the prior year. Smoking status was not assessed. RESULTS: When
      analyzed via Cox proportional hazard regression, the relationship between BMI and
      mortality, represented by means of hazard ratio, was clearly U-shaped for both
      men and women. The base of the curves was fairly wide suggesting that a broad
      range of BMIs are well tolerated by older adults. The minimum mortality
      (estimated from the fitted proportional hazard models) occurred at a BMI of
      approximately 31.7 for women and 28.8 for men. The results were essentially
      unchanged, if analyses were weighted, if various disease states were controlled
      for, and if apparently unhealthy subjects were excluded. CONCLUSIONS: The finding
      of the relatively high BMI (27-30 for men, 30-35 for women) associated with
      minimum hazard in persons older than seventy years supports some previously
      documented findings and opposes others and, if confirmed in future research, has
      implications for public health and clinical recommendations.

PMID- 9192225
TI  - Women's reproductive health: the role of body mass index in early and adult life.
AB  - BACKGROUND: Higher risks of menstrual problems and infertility have been found in
      underweight and overweight women but evidence is inconsistent especially in
      relation to the effect of age of onset of obesity. OBJECTIVE: To determine
      whether body mass index (BMI) in adulthood or childhood affects the reproductive
      health of women. METHODS: Heights, weights (at 7, 11, 16, 23 and 33y) and
      reproductive data were available for 5799 females in the 1958 British birth
      cohort study. Body mass index (BMI) was calculated as weight/height2. Age
      specific cut-offs were used to define overweight and obesity. Reproductive
      outcomes reported at age 33 included: menstrual problems (also reported at 16y),
      hypertension in pregnancy and subfertility. RESULTS: Early menarcheal age was
      associated with higher risks of menstrual problems by 16y but this relationship
      did not persist to 33y. Obesity at 23y and obesity at 7y both independently
      increased the risk of menstrual problems by age 33 (OR = 1.75, OR = 1.59
      respectively) after adjusting for other confounding factors. Obesity at 23y
      increased the risk of hypertension in pregnancy (OR = 2.37), after adjusting for
      confounders. Consistent with these findings, obese women at 23y were less likely
      to conceive within 12 months of unprotected intercourse after adjustment for
      confounders (RR = 0.69). CONCLUSIONS: Overweight and obesity in early adulthood
      appears to increase the risk of menstrual problems, hypertension in pregnancy and
      subfertility. Other than menstrual problems, childhood body mass index had little
      impact on the reproductive health of women.

PMID- 9192226
TI  - Decreased white fat cell thermogenesis in obese individuals.
AB  - OBJECTIVE: To investigate whether white adipocyte thermogenesis and energy
      metabolism are reduced in obese individuals. SUBJECTS: Eight lean and 15 obese
      men and women; BMI 19-41. DESIGN: Isolated subcutaneous adipocytes were
      maintained in agarose gel for 20h under basal conditions and subsequently for 10h
      after stimulation with 1 microM isoprenaline. Direct microcalorimetry was
      performed continuously over 30h while biochemical measures were obtained after 0,
      20, 25 and 30h. MEASUREMENTS: Total cellular thermogenesis, oxygen consumption,
      glycolysis, lipolysis, triglyceride/FFA substrate cycle, adenine nucleotides, DNA
      content as basis of reference. RESULTS: Under basal and stimulated conditions,
      thermogenesis (5.6 and 8.6 microW/microgDNA, respectively; P < 0.0001) correlated
      negatively (P < 0.01 and P < 0.05, respectively) with the BMI and positively with
      O2 and glucose consumption, lactate, glycerol, FFA release and FFA re
      esterification. Reduced basal lactate production with increased BMI (P < 0.05)
      indicates a more aerobic adipocyte metabolism in obese individuals. Negative
      correlation between BMI and stimulated triglyceride/FFA substrate cycle activity
      (P < 0.01) explains the decreased hormone induced adipocyte heat production in
      the obese. CONCLUSIONS: The results suggest that a reduction of total body energy
      expenditure, which is discussed to cause obesity, can be associated with distinct
      metabolic alterations at a cellular level. However, since the estimated total
      body fat cell thermogenesis does not exceed 7% of the resting metabolic rate, the
      observed decrease of adipocyte heat production in the face of augmented BMI can
      only in part be responsible for the development of obesity.

PMID- 9192227
TI  - The relationship between weight and response to cholesterol-lowering diets in
      women.
AB  - OBJECTIVE: To determine whether factors related to body weight might influence
      the cholesterol lowering response to diet. DESIGN: Run-In diet followed by
      crossover to low fat diets; average response is reported. SUBJECTS: Sixty-three
      subjects (30 men and 33 women) with moderately elevated plasma cholesterol
      levels. MEASUREMENTS: Lipid and anthropometric measurements. Data were analyzed
      as a repeated measures analysis of variance with lipid lowering response in all
      combined cholesterol lowering diets compared to baseline. RESULTS: LDL
      cholesterol lowering was significantly affected by BMI in women (P = 0.01) but
      not in men (P = 0.54). There was also a weak effect of waist-hip (W/H) ratio on
      response (P = 0.127) in women, with the lower responders having a higher W/H
      ratio but there was no effect of W/H ratio in men (P = 0.86). CONCLUSION: These
      results suggest that overweight women with elevated plasma cholesterol may be
      less responsive to reducing their cholesterol levels with diet.

PMID- 9192228
TI  - Overweight and obesity in infants of mothers with long-term insulin-dependent
      diabetes or gestational diabetes.
AB  - OBJECTIVES: To analyse the development of body weight and frequencies of
      overweight and obesity in infants of long-term insulin-dependent diabetic mothers
      as compared to those of gestational diabetic mothers. DESIGN: Retrospective
      study. SUBJECTS: Two hundred infants of mothers with pregestational insulin
      dependent diabetes mellitus (IDM) and 117 infants of gestational diabetic mothers
      (IGDM) born between 1980 and 1990 at the Clinic of Obstetrics and Gynaecology,
      Berlin-Kaulsdorf, Germany. MEASUREMENTS: Birth weight, birth length, plasma
      insulin, interscapular skinfold, symmetry index (SI) and body mass index (BMI) at
      birth; SI and BMI in childhood (1-9y of age). RESULTS: Neonatally, mean relative
      weight (SI) was found to be increased in both groups of infants. It was
      positively correlated to interscapular skinfold (P < 0.001) and insulin (P <
      0.005). However, IDM had higher insulin levels (P < 0.001) and a higher frequency
      of obesity (P < 0.05) than IGDM at birth. Throughout childhood frequencies of
      overweight (SI > 1.1) were elevated in both IDM as well as IGDM. In IDM the
      percentage of obesity (SI > 1.2) displayed a significant increase from 11.2% in
      children 1-4y old up to 25.8% at 5-9y (P < 0.05). Similar frequencies and a
      highly significant increase of overweight during childhood of IDM (P < 0.005)
      were observed when BMI > or = 95th percentile was used to determine overweight.
      Relative weight in childhood was positively correlated to relative weight at
      birth (P < 0.05). Large-for-gestational-age infants displayed a significantly
      higher percentage of overweight (SI > 1.1) in childhood than appropriate-for
      gestational-age infants (P < 0.05). CONCLUSIONS: Infants of mothers with diabetes
      during pregnancy are predisposed to develop overweight and obesity during
      childhood. These alterations seem to be related to insulin and relative body
      weight at birth. Pathophysiological mechanisms which might be involved into the
      development of these changes are discussed. Prophylactic measures are recommended
      to reduce morbidity in infants of diabetic mothers.

PMID- 9192229
TI  - Preventing weight gain in adults: design, methods and one year results from the
      Pound of Prevention study.
AB  - OBJECTIVE: To describe the design, methods, and first year results of the Pound
      of Prevention (POP) study, a randomized trial examining whether weight gain with
      age can be prevented using low intensity intervention. DESIGN: Participants were
      randomized to either (1) no-contact control, (2) education through monthly
      newsletters and semiannual classes on nutrition and exercise, and (3) education
      plus a lottery incentive for participation. SUBJECTS: Two hundred and twenty
      eight men, 594 high-income women, and 404 low-income women. Entry requirements
      were age 20-45 y, healthy, and willing to participate for three years.
      MEASUREMENTS: At baseline and one year later, participants were weighed and
      completed questionnaires about behaviors and attitudes related to weight and
      weight control. RESULTS: Mean body mass indices at baseline were 28.1, 26.1, and
      28.2 for men, high-income women and low-income women, respectively. After one
      year, participants in the intervention conditions reported significantly
      increased frequency of weight monitoring, but no change in other targeted
      behaviors. One year weight changes in the control, education, and education plus
      lottery groups were 1.94 lb, 0.72 lb, and 0.21 lb in men; 1.38 lb, 1.03 lb, and
      0.51 lb in high-income women; and 1.30 lb, 2.11 lb, and 3.23 lb in low-income
      women. CONCLUSIONS: These one-year results suggest that the intervention may be
      having a greater impact on high than low-income participants.

PMID- 9192230
TI  - Appearance of brown adipocytes in white adipose tissue during CL 316,243-induced
      reversal of obesity and diabetes in Zucker fa/fa rats.
AB  - BACKGROUND: In our previous studies, chronic treatment of rats with a new beta 3
      adrenoceptor agonist, CL 316,243, retarded diet-induced obesity and promoted
      thermogenesis in young animals and reversed established diet-induced obesity in
      older animals that continued to eat a high fat diet. Reversal of obesity was
      associated with shrinking of enlarged white adipocytes but the number of mature
      white adipocytes, which had not been increased by the diet, was not reduced. Drug
      treatment induced appearance of abundant brown adipocytes in white adipose tissue
      (WAT) depots as well as hypertrophy of brown adipose tissue (BAT) in both lean
      and diet-induced obese rats. OBJECTIVES: To find out whether the known
      hyperplasia of white adipocytes in the obese fa/fa rat could be reversed by CL
      316,243-treatment and whether the grossly enlarged WAT depots of the obese fa/fa
      rat contain precursors to brown adipocytes. RESULTS: CL 316,243 infusion (1
      mg/kg/d) reduced abdominal fat. The loss of fat was due to a decrease in white
      adipocyte size, with no loss of the markedly elevated number of adipocytes in the
      fa/fa rats. Resting metabolic rate increased by 40% in lean rats, by 70% in fa/fa
      rats. Food intake decreased in the hyperphagic fa/fa rats but did not change in
      lean rats, in both lean and fa/fa rats, a marked increase in protein content of
      retroperitoneal WAT was associated with appearance of abundant densely-stained
      brown adipocytes expressing uncoupling protein (UCP) but total number of cells
      (from DNA content) actually decreased. Hyperinsulinemia and hyperglycemia of
      fa/fa rats were reduced by treatment, indicating improved sensitivity to insulin.
      CONCLUSIONS: Abundant precursors to brown adipocytes are present in WAT depots of
      fa/fa rats and much of the exaggerated increase in resting metabolic rate induced
      by CL 316,243 occurs in these cells. This beta 3-adrenoceptor agonist is an
      effective anti-obesity and anti-diabetic agent in fa/fa rats. It does not bring
      about disappearance of mature white adipocytes but does bring about a remodelling
      of WAT, with a marked change in cell composition.

PMID- 9192231
TI  - Impact of waist-hip-ratio and body-mass-index on hormonal and metabolic
      parameters in young, obese women.
AB  - BACKGROUND: To investigate the impact of predominantly upper body fat
      localisation on the hormonal and metabolic profile in obese, infertile women.
      DESIGN: Prospective observational study of premenopausal women with obesity,
      infertility and menstrual dysfunction. SETTING: Department of Endocrinology and
      Reproduction of the University Hospital of Obstetrics and Gynaecology of
      Heidelberg. SUBJECTS: Eighteen women with android type obesity (waist-hip-ratio =
      WHR > 0.85, group 1) and 22 women with gynoid type obesity (WHR < or = 0.85,
      group 2) in a group of 58 premenopausal obese women (median age 28 y) with
      infertility. Twenty-nine women took part in a weight reducing program lasting 32
      +/- 14 (mean +/- s.d.) weeks. MEASUREMENTS: BMI, WHR and blood pressure. Plasma
      lipids and liver enzymes. Blood glucose, insulin, C-peptide and different steroid
      and pituitary hormones during oral glucose loading. RESULTS: In the total group
      of 58 obese women, WHR was directly correlated to plasma triglycerides, AST, ALT
      and cholesterol/HDL-cholesterol-ratio. WHR correlated inversely with HDL
      cholesterol. Insulin resistance was greater with increasing WHR. Systolic blood
      pressure, glucose, insulin, C-peptide, triglycerides, cholesterol/HDL-cholesterol
      ratio, aspartate (AST) and alanine aminotransferase (ALT) were significantly
      greater in group 1. Group 2 had greater HDL-cholesterol levels. One subject in
      group 1, five women in group 2 conceived spontaneously after weight reduction.
      CONCLUSIONS: Determination of the WHR is a simple measurement to identify obese
      patients who are at a greater risk of developing the metabolic syndrome. WHR is
      important in preventive medicine, as typical metabolic profiles are already
      present in young women before clinical manifestation. Women with android obesity
      seem to be more prone to develop menstrual irregularity and infertility. The
      hyperinsulinaemia may be the pathway.

PMID- 9192232
TI  - Body mass index variations by age and sex, and prevalence of overweight in
      Japanese adults.
AB  - OBJECTIVE: To determine the reference value of BMI for Japanese subjects and to
      estimate the prevalence of overweight based on this reference value. DESIGN:
      Epidemiological analysis with the LMS method, which provides a way of obtaining
      normalized BMI distributions. SUBJECTS: 7508 Japanese subjects aged 18-69 y in
      1993. MEASUREMENTS: Height, age and body weight. CALCULATION: BMI was calculated
      and tables for percentiles of BMI were plotted against age and sex. Furthermore,
      the prevalence of overweight was estimated based on 85th percentile of BMI in the
      men and women 20-29 y of age, who were considered the reference group. RESULTS:
      The geometric mean BMI and the prevalence of overweight in men was highest in the
      30-39 y age group. For women the maximum BMI and prevalence of overweight
      occurred in the decade 50-59 y. The cut-off points for overweight in this sample
      were 24.7 kg/m2 for men and 22.6 kg/m2 for women. These are considerably lower
      than the figures of 27.8 kg/m2 and 27.3 kg/m2 estimated for Americans.
      CONCLUSIONS: The prevalence of obesity in Japanese populations should be
      estimated using ethnic specific values of BMI, rather than those drawn from
      Caucasians who tend to have higher BMI in each age group. The prevalence of
      overweight is increased as age increased in both sexes, especially in women.

PMID- 9192233
TI  - Novel polymorphism of the human ob gene promoter in lean and morbidly obese
      subjects.
AB  - OBJECTIVE: Leptin, the circulating product of the human ob gene, may play role in
      control of appetite and metabolic rate. We screened the proximal promoter area of
      the ob gene for mutations and common polymorphisms in order to find out whether
      genetic variation in the regulatory area of this gene plays a role in human
      obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP)
      was applied to screen for the promoter area of the ob gene for genetic
      alterations in morbidly obese patients. SUBJECTS: A total of 249 morbidity obese
      (present or past body mass index [BMI] > or = 40 kg/m2) and 141 lean (BMI < or =
      25 kg/m2) subjects. MEASUREMENTS: DNA analysis was carried out using a single
      strand conformation polymorphism (SSCP) technique and PCR followed by digestion
      with the restriction enzyme BssHll. Leptin was determined by radioimmunoassay in
      obese subjects. Serum lipids, glucose and insulin concentrations in the obese
      subjects were also determined. RESULTS: A new polymorphism C(-188)A was
      identified in the promoter region of the ob gene. This polymorphism was detected
      with allelic frequencies of 0.06 in morbidly obese subjects and 0.09 in lean
      controls (P = 0.28). Initial studies failed to show an association of this
      polymorphism with serum leptin, response to treatment for obesity, history and
      extent of weight gain, or serum insulin, glucose of lipid concentrations.
      CONCLUSIONS: We have identified a common polymorphism in the promoter area of the
      human ob gene which appears to be very useful for genetic association and linkage
      studies. Further studies are needed to elucidate its potential role in the
      regulation of the human ob gene and in human metabolic disorders.

PMID- 9192234
TI  - Removal of endogenous leptin from the circulation by the kidney.
AB  - OBJECTIVE: This study was performed to test the hypothesis that the kidneys play
      a primary role in the clearance of endogenous leptin from the circulation of
      obese rats. DESIGN: Zucker (fa/fa) obese rats were anaesthetized and subjected to
      various surgical manipulations of the kidneys. One hour after surgery arterial
      blood samples were taken at 1 h intervals for times upto 8 h. Plasma leptin
      concentrations were determined by radioimmunoassay. RESULTS: Bilateral
      nephrectomy induced a rapid increase in plasma leptin concentrations above
      control values. In contrast, continuous intravenous re-injection of voided urine
      did not increase circulating leptin concentrations, indicating that leptin is not
      present in the urine in large quantities. This conclusion was confirmed by the
      very low levels of detectable leptin in urine. Leptin is not metabolized across
      the renal circulation and is extracted intact by the kidney. Simultaneous
      measurement of renal plasma flow established renal leptin extraction at
      approximately 59 ng/ min for both kidneys. Following intravenous infusion of
      leptin, renal clearance and whole body clearance were equal. This finding
      indicates that the kidneys alone are responsible for the systemic elimination of
      leptin in Zucker rats. Seven hours after bilateral ureteral ligation, a procedure
      which lowers glomerular filtration, plasma leptin concentrations were elevated.
      The renal extraction of leptin did not change over a wide range of plasma leptin
      concentrations suggesting that renal leptin extraction is a high capacity, non
      saturable process most probably glomerular filtration. CONCLUSION: Endogenous
      leptin is rapidly cleared from the circulation by the kidney by glomerular
      filtration followed by metabolic degradation in the renal tubules.

PMID- 9192235
TI  - Determining the optimum dose for the intravenous administration of nicardipine in
      the treatment of acute heart failure--a multicenter study. The Nicardipine Heart
      Failure Study Group.
AB  - Nicardipine is a potent arteriolar vasodilator with a negligible negative
      inotropic effect. Although intravenous administration of this drug has been
      reported to be effective in the treatment of heart failure, the optimal dose by
      this route is not clear. This study was designed to determine the optimum dose
      for the intravenous infusion of nicardipine in the treatment of heart failure. In
      Trial 1, nicardipine was administered intravenously at a dose of 0.5 microgram/kg
      per min to 14 patients with acute heart failure. The dose was increased to 1.0
      microgram/kg per min in 13 cases with marked improvement at 2 h. In Trial 2,
      nicardipine was administered in a double-blind manner to 53 patients at 3
      different rates of infusion for 2 h: 1.0 (Group 1, n = 19), 2.0 (Group 2, n =
      15), and 3.0 (Group 3, n = 19) micrograms/kg per min. Neither heart rate nor mean
      right atrial pressure changed in any of the 3 groups. Favorable hemodynamic
      effects were evident in all groups beginning 30 min after the start of infusion,
      with an increase in cardiac index (control vs 2 h after infusion, L/min per m2)
      (Group 1: 2.2 +/- 0.4 vs 3.1 +/- 0.8, Group 2: 2.2 +/- 0.4 vs 2.9 +/- 0.5, Group
      3: 2.3 +/- 0.3 vs 3.1 +/- 0.7, all p < 0.01 compared to the control) and a
      decrease in diastolic pulmonary artery pressure (Group 1: 26 +/- 10 vs 19 +/- 7,
      Group 2: 27 +/- 10 vs 20 +/- 8, Group 3: 26 +/- 7 vs 18 +/- 5 mmHg, all p <
      0.01). The decrease in systolic pressure was greatest in Group 3 (Group 1: 141 +/
      31 vs 119 +/- 18, Group 2: 149 +/- 25 vs 118 +/- 17, Group 3; 147 +/- 27 vs 107
      +/- 14 mmHg, all p < 0.01 compared to control, and p < 0.05 between Groups 1 and
      3). The intravenous drip infusion of nicardipine is effective in the treatment of
      heart failure by inducing an increase in cardiac output and a decrease in
      pulmonary artery wedge pressure. The optimal dose in this study was 1.0
      microgram/kg per min.

PMID- 9192236
TI  - Balloon angioplasty for aortic coarctation--report of a questionnaire survey by
      the Japanese Pediatric Interventional Cardiology Committee.
AB  - The aim of this study was to analyze the results of a questionnaire survey
      regarding acute and late effects of balloon angioplasty for aortic coarctation in
      Japan. Considerable controversy still exists regarding the effectiveness and
      safety of balloon angioplasty in native coarctation. Moreover, little information
      about this mode of treatment is available from Japan. A questionnaire was sent to
      55 Japanese institutions with pediatric cardiology units. A total of 208 patients
      from 35 institutions were reported and analyzed for indications for balloon
      angioplasty, acute and late results, and complications. Balloon angioplasty was
      performed in 56 patients with native coarctation (group I) and in 152 patients
      with postoperative recoarctation (group II). In group I, the pressure gradient
      across the coarcted site decreased significantly from 34 +/- 19 to 16 +/- 21 mmHg
      (p < 0.001), and the diameter of the coarcted site increased significantly from
      3.7 +/- 1.7 to 6.0 +/- 2.5 mm (p < 0.001). In group II the pressure gradient
      significantly decreased from 41 +/- 20 to 15 +/- 15 mmHg (p < 0.001) and the
      diameter of the coarcted site significantly increased from 4.2 +/- 2.2 to 6.8 +/-
      3.1 mm (p < 0.001). The restenosis rate was significantly higher in group I
      (19/41, 46%) than in group II (25/139, 18%) (p = 0.0006). Redilation was
      successfully performed in 27 of 29 of the patients with restenosis. Major
      complications included femoral pulse loss, transient bradycardia, and arrhythmia.
      No patient died of a cardiac event related to the procedure. The significant risk
      factors for late restenosis included type of coarctation, age under 4 months,
      balloon size used, pressure gradient and coarctation diameter before the
      procedure. Balloon angioplasty is a suitable treatment for aortic coarctation in
      both native coarctation and postoperative recoarctation. Restenosis was
      significant after initial balloon angioplasty in native coarctation but
      redilation was effective in most cases. The most significant risk group for
      restenosis is young children with native coarctation.

PMID- 9192237
TI  - Microatelectasis in patients with secundum atrial septal defect and its relation
      to pulmonary hypertension.
AB  - In patients with secundum atrial septal defect, pulmonary hypertension appears to
      be attributable to microatelectasis of the lung. To confirm this hypothesis,
      pulmonary arteries in surgical biopsy specimens from 72 patients with atrial
      septal defect and pulmonary hypertension were subjected to morphometric
      examination. Thirty eight of the 72 patients (53%) were found to have
      microatelectasis of the lung, which suggests that an even higher frequency would
      have been found if the entire organ had been examined. Atelectatic changes were
      found in 21 of 39 patients with plexogenic pulmonary arteriopathy (54%), 8 of 15
      with musculoelastosis (53%), and 9 of 13 with both of these lesions (69%). No
      such changes were observed in 5 patients with atrial septal defect who showed
      thromboembolism-type lesions of the pulmonary arteries. On the other hand,
      microatelectasis was not observed in another 5 patients with atrial septal defect
      who did not exhibit pulmonary hypertension. The medial smooth muscles of
      pulmonary arteries in atelectatic areas were thicker (16.4 +/- 4.0 microns) than
      those in non-atelectatic areas (10.3 +/- 3.3 microns). The index of pulmonary
      vascular disease was not significantly different between atelectatic (2.0 +/-
      0.6) and non-atelectatic areas (1.9 +/- 0.5). We conclude that in
      microatelectatic areas, which may tend to develop after respiratory infections in
      patients with atrial septal defect, hypoxic vasoconstriction of the small
      pulmonary arteries is liable to occur, which causes hypertrophy of the media.
      This is likely to lead to the elevation of pulmonary arterial pressure and
      sustained pulmonary hypertension.

PMID- 9192238
TI  - Effect of coronary risk factors on coronary angiographic morphology in patients
      with ischemic heart disease.
AB  - We investigated the effects of hypercholesterolemia, hypertension, and diabetes
      mellitus, which are major coronary risk factors, on the angiographic morphology
      of coronary artery lesions in 204 patients with previous myocardial infarction or
      stable-effort angina: 39 patients with hypercholesterolemia (serum total
      cholesterol > 240 mg/dl) without hypertension and diabetes, 51 patients with
      hypertension without diabetes and hypercholesterolemia, 24 patients with diabetes
      without hypertension and hypercholesterolemia, and 90 patients without any of
      these 3 risk factors (control). Patients without coronary artery lesions were
      excluded. The severity of coronary artery lesions is expressed as the Gensini
      score and the morphology is classified according to Rosch's classification. The
      distribution of coronary artery lesions did not differ significantly between the
      4 groups. The Gensini score was significantly higher in the hypercholesterolemia
      group than in the other groups (p < 0.05). Short concentric lesions were more
      frequent in the hypercholesterolemia group than in the control group (p < 0.01),
      and tubular regular lesions were more frequent in the hypertension and diabetes
      groups than in the control group (p < 0.01). These results suggest that
      hypercholesterolemia has a greater influence on the severity of coronary artery
      lesions than does hypertension or diabetes, and that the progression of coronary
      atherosclerosis may differ among patients with these risk factors.

PMID- 9192239
TI  - Postoperative influences of surgical cryoablation for Wolff-Parkinson-White
      syndrome--a analysis of myocardial enzymes and function.
AB  - We evaluated postoperative myocardial enzymes and function associated with
      cryoablation in 20 patients with Wolff-Parkinson-White syndrome undergoing
      surgical treatment for a single left-sided accessory conduction pathway. Ten
      patients underwent endocardial atrial incision with cryoablation using CO2 at -60
      degrees C for 120 sec (group A), while the remaining 10 patients did not receive
      cryoablation (group B). Levels of aspartate aminotransferase (GOT), lactate
      dehydrogenase (LDH), and creatine kinase (CK-MB) on postoperative days 1, 2, and
      3 were higher in patients in group A than in group B (p < 0.05). However, mean
      values remained low (GOT, 120.5 IU/L; LDH, 1105.1 IU/L; CK-MB, 76.3 IU/L). No
      electrocardiographic changes were detected. Parameters of cardiac function,
      including cardiac index, stroke volume index, systemic vascular resistance, and
      ejection fraction, remained unchanged during the postoperative period in both
      groups. Furthermore, 201Tl cardiac scintigraphy demonstrated no evidence of
      myocardial perfusion defects due to cryoablation in group A. In conclusion,
      myocardial damage induced by cryoablation is very minor and is not associated
      with any clinical impairment of cardiac function.

PMID- 9192240
TI  - Alveolar-arterial gas tension differences during progressive exercise in patients
      after the Fontan operation.
AB  - We investigated alveolar-arterial gas tension differences as a measurement of
      ventilatory impairment during exercise in patients who had undergone the Fontan
      operation. The ventilatory response to exercise in 13 operated patients was
      compared with that of 11 control subjects. The difference between end-tidal and
      arterial oxygen tension (P(ET-a)DO2) and between arterial and end-tidal carbon
      dioxide tension (P(a-ET)DCO2) as well as the physiologic dead space-tidal volume
      ratio were calculated during progressive treadmill exercise testing. In the
      Fontan group, P(ET-a)DO2 and P(a-ET)DCO2 were significantly higher than in
      control subjects and increased in parallel during the study period. The
      physiologic dead space-tidal volume ratio was higher in the Fontan group than in
      the control group, and the difference in these ratios between the values obtained
      using end-tidal carbon dioxide tension and those using arterial carbon dioxide
      tension correlated well with P(a-ET)DCO2 (r = -0.79 to -0.98, p < 0.001). The
      physiologic dead space-tidal volume ratio during exercise was significantly
      higher in patients with low exercise capacities than in those with high exercise
      capacities (p < 0.05). The alveolar-arterial gas tension differences during
      exercise were greater in Fontan patients than in control subjects. We conclude
      that the size of the physiologic dead space can be evaluated from measurements of
      arterial carbon dioxide tension and is correlated with impaired exercise capacity
      after the Fontan operation.

PMID- 9192241
TI  - Prolonged arterial occlusion caused by thrombus development at sites of arterial
      bifurcation.
AB  - Although thrombogenic atheromas frequently develop at sites of arterial branching
      or bifurcation, the nature of such thrombus formation remains unclear. In this
      study, small rat mesenteric arteries (about 0.3 mm id) were observed using a
      video-microscope system. Exposure of the media by inducing compression damage
      over a short segment caused occlusive thrombus formation and subsequent
      spontaneous reperfusion repeatedly over about 30 min. Compression damage was
      induced either at a site just distal to the bifurcation (group 1, n = 7) or 5-10
      mm downstream from the bifurcation (group 2, n = 7). The number of thrombotic
      occlusions was similar in the 2 groups, but the total duration of occlusion was
      significantly higher in group 1 (540 +/- 47 sec) than in group 2 (295 +/- 24 sec)
      (p < 0.01). The total duration of occlusion in group 1 was significantly reduced
      to 273 +/- 16 sec (p < 0.01) by mechanical interruption of flow in the other,
      intact, arterial branch. In the presence of blood flow through the intact branch,
      the occlusive thrombus at the bifurcation further enlarged in the direction of
      the intact branch, resulting in a significantly larger thrombus than in the
      absence of blood flow (17.1 +/- 2.1 vs 9.2 +/- 0.9 x 10(-2) mm2, p < 0.01).
      Stasis of the arterial blood per se did not affect the duration of thrombotic
      occlusion or increase plasma fibrinolytic activity. Thus, arterial occlusion
      caused by a thrombus arising at arterial bifurcations may be prolonged because of
      enlargement of the thrombus owing to the action of platelets in blood flowing
      through the intact branch.

PMID- 9192242
TI  - Cardiovascular and renal effects of the combination of felodipine and metoprolol
      during a high-salt and a moderate-salt diet in spontaneously hypertensive rats.
AB  - In the present study the influence of dietary salt on the cardiovascular and
      renal effects of the calcium channel blocker felodipine (1.2 mg/kg sc) and the
      beta 1-adrenoceptor blocking drug metoprolol (250 mg/kg po), alone and in
      combination, was examined in the spontaneously hypertensive rats (SHRs) in a 4
      week study. In addition, the influence of different diet and drug regimens on
      vascular functions was assessed by measuring the vascular relaxation and
      contractile responses of mesenteric arterial rings in vitro at the end of the
      experimental period. In SHRs, a high-salt diet caused a marked rise in blood
      pressure, impaired the endothelium-dependent vascular relaxation responses to
      acetylcholine and induced left ventricular hypertrophy (LVH) and renal
      hypertrophy. Metoprolol had little if any effect on salt-induced changes in blood
      pressure, endothelium-dependent vascular relaxation or renal hypertrophy, but it
      partially prevented the development of salt-induced LVH. Felodipine during the
      high-salt diet lowered blood pressure to normotensive level and completely
      prevented salt-induced left ventricular and renal hypertrophy as well as
      endothelial dysfunction. Felodipine produced tachycardia, especially at the
      beginning of drug treatment. The combination of felodipine and metoprolol
      abolished the effects of the individual drugs on heart rate. The drug combination
      also completely prevented the detrimental cardiovascular and renal effects
      induced by a high salt intake. Although salt restriction did not further enhance
      the profound antihypertensive effect of the combination of metoprolol and
      felodipine, it enhanced the effects of the drug combination on LVH and renal
      hypertrophy. Our findings indicate that felodipine treatment, alone and in
      combination with metoprolol, normalizes blood pressure and prevents the
      development of salt-induced LVH and renal hypertrophy. During the high-salt diet
      the beneficial vascular effects of felodipine as well as those of the combination
      of felodipine and metoprolol are mediated, at least in part, by prevention of
      salt-induced endothelial dysfunction. The only apparent benefit from the use of
      metoprolol in combination with a relatively high dose of felodipine was the
      prevention of tachycardia.

PMID- 9192243
TI  - Dynamic intravenous coronary arteriography using synchrotron radiation and its
      application to the measurement of coronary blood flow.
AB  - We have developed dynamic intravenous coronary arteriography (IVCAG) using a
      monochromatic (33.3 keV), 2-dimensional X-ray beam (70 x 70 mm) generated from
      synchrotron radiation. To investigate its use to visualize the coronary arteries
      and to estimate coronary blood flow, we performed IVCAG in 10 dogs and 1 goat.
      The animals were irradiated with the synchrotron beam after intravenous injection
      of a contrast agent, and images were obtained using a TV camera and
      videorecorder. In the dogs, blood flow in the left anterior descending coronary
      artery (LAD) was also estimated from the images by applying a transit-time
      analysis. We obtained dynamic IVCAG images in the dogs and goat and could
      visualize even a deliberately created coronary stenosis about 1 mm in length. In
      addition, coronary blood flow could be estimated with an acceptable degree of
      accuracy. LAD flow calculated from IVCAG was 14.7 +/- 5.1 ml/min, whereas
      measured LAD flow was 16.6 +/- 4.8 ml/min. There was a close correlation between
      the estimated and measured LAD flows (r = 0.90, p < 0.01). Thus, dynamic IVCAG is
      minimally invasive, permits the simultaneous evaluation of coronary anatomy and
      blood flow, and may be feasible for clinical application.

PMID- 9192244
TI  - Roles of nitric oxide and adenosine in the regulation of coronary conductance in
      the basal state and during reactive hyperemia.
AB  - Nitric oxide (NO) and adenosine are important mediators in the regulation of
      coronary vascular tone and are released into the interstitium from the vascular
      endothelium and myocardium, respectively. The roles of these autacoids in the
      regulation of coronary flow in the basal and reactive hyperemic states were
      examined in Langendorff rabbit hearts perfused with oxygenated Krebs-Henseleit
      solution at 37 degrees C and 110 mmHg pressure. Instantaneous perfusion pressure
      flow relationships were analyzed to derive coronary conductance both in the basal
      state and during the early phase of reperfusion (hyperemic state). N omega-nitro
      L-arginine methyl ester (L-NAME) at increasing concentrations (10(-6) to 10(-4)
      mol/L) (n = 7) and 8-phenyltheophylline (8-PT) at increasing concentrations (10(
      9) to 10(-6) mol/L) (n = 7) were applied to assess the role of NO and adenosine,
      respectively. L-NAME dose-dependently reduced the coronary conductance in both
      the basal and early hyperemic states, while 8-PT dose-dependently reduced
      conductance only in the hyperemic state. Changes in conductance during the early
      hyperemic phase correlated well with changes in the debt repayment ratio for
      either L-NAME (r = 0.94) or 8-PT (r = 0.99). These data suggest that a flow
      related NO release mechanism regulates the coronary conductance in both the basal
      and hyperemic states while the metabolic regulation of adenosine release plays a
      role in the presence of ischemia.

PMID- 9192245
TI  - Arthritis and meningitis--the first manifestations of bacterial endocarditis in 2
      patients.
AB  - We have encountered 2 patients in whom the first manifestations of bacterial
      endocarditis were arthritis (in 1 case septic arthritis and in the other
      nonseptic arthritis) and bacterial meningitis. These presentations were followed
      by acute heart failure due to aortic valve destruction, although the patients
      showed no significant cardiovascular manifestations on admission. Aortic valve
      replacement was performed in each case and the patients' postoperative course was
      comfortable. We would like to emphasize the following points. (1) Arthritis and
      meningitis are uncommon in patients with bacterial endocarditis. However, it is
      necessary to consider the possibility of bacterial endocarditis when these
      clinical manifestations present together. Such a combination can cause rapid
      valve destruction. When more than 2 rare complications of bacterial endocarditis
      coexist, surgery should be considered as soon as the definite diagnosis of
      bacterial endocarditis is established, even if congestive heart failure has not
      yet developed. (2) Arthritis associated with bacterial endocarditis might be
      truly septic rather than mediated by circulating immune complexes as is commonly
      believed.

PMID- 9192246
TI  - Disappearance of the 'no-reflow' phenomenon after adjunctive intracoronary
      administration of nicorandil in a patient with acute myocardial infarction.
AB  - Adjunctive intracoronary administration of nicorandil, an ATP-sensitive potassium
      channel opener, after successful coronary revascularization was performed in a 54
      year-old patient with acute myocardial infarction. The 'no-reflow' phenomenon
      disappeared after nicorandil administration and significant functional recovery
      of the infarcted myocardium was achieved. This suggests that nicorandil could
      eliminate the 'no-reflow' phenomenon after successful coronary revascularization.

PMID- 9192247
TI  - [Effect of imipenem/cilastatin combined with vancomycin for MRSA infection].
AB  - Therapeutic efficacy of the combined regimen, imipenem/cilastatin (IPM/CS) plus
      vancomycin (VCM), was examined in a total of 13 patients infected with MRSA (10
      patients with pneumonia, 2 with sepsis and 1 with urinary tract infection). Based
      on the results of determination of FIC indices, in vitro combined effects were
      synergistic in 4 strains and additive in 3 strains. There was, however, no
      apparent correlation between the in vitro combined effect in terms of FIC index
      and clinical outcome. No side effects or abnormal laboratory findings were
      observed. The average daily doses of IPM/CS and VCM were 1.2 g and 1.25 g and the
      average administration periods were 17.5 and 14.9 days, respectively. The present
      results suggested that simultaneous use of IPM/CS and VCM at the standard doses
      could yield an enhancement of both bacteriological and clinical efficacies in
      treatment of the patients with MRSA infection.

PMID- 9192248
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1995). III.
      Differences in susceptibilities from previous years].
AB  - Susceptibilities to various antimicrobial agents were examined for Enterococcus
      faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and
      Pseudomonas aeruginosa that were isolated from patients with urinary tract
      infections (UTIs) in 11 hospitals during June, 1995 through May, 1996, and the
      results were compared with those obtained during the same period in earlier
      years. 1. Macrolide resistant E. faecalis isolated from uncomplicated UTIs during
      the latest study period appeared to have increased compared to those in previous
      study periods. More than 50% of the isolated E. faecalis during the latest study
      period were resistant to macrolide antibiotics, for the first time in our
      history. 2. No obvious changes were observed through the years for
      susceptibilities of S. aureus to various antimicrobial agents. Vancomycin (VCM)
      showed the highest activity against S. aureus, with MICs below 2 micrograms/ml or
      below. 3. Among E. coli strains, those with low susceptibilities to quinolones
      appeared to have increased over the years with MIC90 changed from between 0.125
      microgram/ml or below and 0.5 microgram/ml in the 1989-1990 period to between 8
      micrograms/ml and 128 micrograms/ml in the latest study period. 4. Klebsiella
      spp. showed higher resistance to most antimicrobial agents during periods of 1993
      1994 and 1994-1995, but somewhat lower resistance during period of 1995-1996. No
      resistant Klebsiella spp. were detected from uncomplicated UTIs during the latest
      study period. 5. Among P. aeruginosa isolates from complicated UTIs, resistance
      isolates to gentamicin appeared to be increasing over the years. Resistant
      strains to quinolones were isolated at lower frequencies during periods of 1991
      1994, but higher frequency was observed in the latest period, and MIC50s were
      between 0.5 and 4 micrograms/ml during 1991-1994, but were 16-32 micrograms/ml
      during 1995-1996. These susceptibility changes should be utilized in determining
      clinical treatments.

PMID- 9192249
TI  - [Combination effect between panipenem and vancomycin on highly methicillin
      resistant Staphylococcus aureus].
AB  - We investigated the in vitro and in vivo combination effects between panipenem
      (PAPM) and vancomycin (VCM) on highly methicillin-resistant strains of
      Staphylococcus aureus (MRSA) isolated from various clinical specimens.
      Examination of combination between panipenem and vancomycin using checkerboard
      titration showed a good effect with mean fractional inhibitory index of 0.32 +/-
      0.12 on 40 MRSA strains, and the effects were judged as synergistic against 33
      strains (83%) and additive against 7 strains (17%). In the combination of PAPM
      and VCM at 1/4 MIC each against exponentially growing MRSA, bactericidal activity
      was found when PAPM was added at 1 hour or 2 hours prior to VCM-addition, and
      PAPM with VCM was added simultaneously, although bactericidal activity was
      scarcely demonstrated when VCM was added at 1 hour or 2 hours prior to PAPM
      addition. Bactericidal activity was enhanced against MRSA in the combination of
      PAPM and VCM at 1/4 MIC each for MRSA than the bactericidal activity of VCM at 1
      MIC alone, and the combination showed a strong bactericidal activity against P.
      aeruginosa. VCM alone, however, had no bactericidal activity in the in vitro
      mixed cultures of the two bacteria. Furthermore, the combination of PAPM and VCM
      induced a marked damage to cell surface and bacteriolysis against MRSA and P.
      aeruginosa in the mixed cultures, although VCM alone induced only slight
      morphological alterations. Penicillin-binding proteins (PBPs) including MRSA
      specific PBP 2' were decreased greatly in the amounts in MRSA-cells with the
      increase of VCM-treated concentration. The combination therapy of PAPM and VCM
      showed a greater efficacy than the therapeutic efficacy of each antibiotic alone
      against mixed infection in burned mice caused by MRSA and P. aeruginosa, and the
      activity was judged as synergistic based on the FED index smaller than 0.34.

PMID- 9192250
TI  - How doctors and patients discuss routine clinical decisions. Informed decision
      making in the outpatient setting.
AB  - OBJECTIVE: To characterize the informed consent process in routine, primary care
      office practice. DESIGN: Cross-sectional, descriptive evaluation of audiotaped
      encounters. SETTING: Offices of primary care physicians in Portland, Oregon.
      PARTICIPANTS: Internists (54%) and family physicians (46%), and their patients.
      MEASUREMENTS AND MAIN RESULTS: Audiotapes of primary care office visits from a
      previous study of doctor-patient communication were coded for the number and type
      of clinical decisions made. The discussion between doctor and patient was scored
      according to six criteria for informed decision making: description of the nature
      of the decision, discussion of alternatives, discussion of risks and benefits,
      discussion of related uncertainties, assessment of the patient's understanding
      and elicitation of the patient's preference. Discussions leading to decisions
      included fewer than two of the six described elements of informed decision making
      (mean 1.23, median 1.0), most frequent of these was description of the nature of
      the decision (83% of discussion). Discussion of risks and benefits was less
      frequent (9%), and assessment of understanding was rare (2%). Discussions of
      management decisions were generally more substantive than discussions of
      diagnostic decisions (p = .05). CONCLUSIONS: Discussions leading to clinical
      decisions in these primary care settings did not fulfill the criteria considered
      integral to informed decision making. Physicians frequently described the nature
      of the decision, less frequently discussed risks and benefits, and rarely
      assessed the patient's understanding of the decision.

PMID- 9192251
TI  - Preferences of physicians and their patients for end-of-life care.
AB  - OBJECTIVE: Both physicians and patients view advance directives as important, yet
      discussions occur infrequently. We assessed differences and correlations between
      physicians' and their patients' desires for end-of-life care for themselves.
      MEASUREMENTS AND MAIN RESULTS: Study physicians (n = 78) were residents and
      faculty practicing in an inner-city, academic primary care general internal
      medicine practice. Patients (n = 831) received primary care from these physicians
      and were either at least 75 or between 50 and 74 years of age, with selected
      morbid conditions. Physicians and patients completed identical questionnaires
      that included an assessment of their preferences for six specific treatments if
      they were terminally ill. There were significant differences between physicians'
      and patients' preferences for all six treatments (p < .0001), with physicians
      wanting less treatment than their patients for five of them. Patients desiring
      more care (p < .01) were more often male (odds ratio [OR] 1.7). African-American
      (OR 1.6), and older (OR 1.02 per year). There were no such correlates with
      physicians' preferences. A treatment preference score was calculated from
      respondents' desires to receive or refuse the six treatments. Physicians' scores
      were highly correlated with those of their enrolled primary care patients (r =
      .51, p < .0001). CONCLUSIONS: Although patients and physicians as groups differ
      substantially in their preferences for end-of-life care, there was significant
      correlation between individual academic physicians' preferences and those of
      their primary care patients. Reasons for this correlation are unknown.

PMID- 9192252
TI  - The impact of feedback to medical housestaff on chart documentation and quality
      of care in the outpatient setting.
AB  - OBJECTIVE: To determine whether feedback from attending physicians to residents
      about outpatient medical records improves chart documentation and quality of
      care. DESIGN: Cross-sectional study with repeated measures. SETTING: Primary care
      internal medicine clinic at a metropolitan community hospital.
      PATIENT/PARTICIPANTS: Fifteen interns and 20 residents. INTERVENTION: Attending
      physicians reviewed at least two charts for each resident on three occasions
      about 4 months apart and then discussed their findings with the residents.
      MEASUREMENTS AND MAIN RESULTS: Explicit criteria defined the extent of chart
      documentation and the comprehensiveness of care delivery. Attending physicians
      also made a subjective assessment of the overall quality of care. All results
      were converted to 0-to-1 scales. From the first to the third period, chart
      documentation increased from 0.60 to 0.86 (p < .001), but there were no
      significant changes in the delivery of care or in the subjective assessments of
      the overall quality of care. CONCLUSIONS: Both review of residents' outpatient
      medical records and periodic feedback from attending physicians improve how well
      medical housestaff document care in the chart.

PMID- 9192255
TI  - Why should I live in pain?

PMID- 9192253
TI  - Redesigning primary care processes to improve the offering of mammography. The
      use of clinic protocols by nonphysicians.
AB  - OBJECTIVE: To develop, within the framework of continuous quality improvement,
      new processes for offering mammography and determine whether protocols executed
      completely by nonphysicians would increase mammography utilization. DESIGN: A
      prospective follow-up study with patients from an intervention clinic and two
      control clinics. SETTING: Three general internal medicine clinics in a large,
      urban teaching hospital in Detroit, Michigan. PATIENTS/PARTICIPANTS: A total of
      5,934 women, aged 40 through 75 years, making 16,546 visits to one of the clinics
      during the study period (September 1, 1992, through November 31, 1993).
      INTERVENTION: Medical assistants and licensed practical nurses in the
      intervention clinic were trained to identify women due for screening mammography,
      and to directly offer and order a mammogram if patients agreed. MEASUREMENTS AND
      MAIN RESULTS: Patients were considered up-to-date with screening if they had a
      mammogram within 1 year (if age 50-75) or 2 years (if age 40-49) prior to the
      visit or a mammogram within 60 days after the visit. The proportion of visits
      each month in which a woman was up-to-date with mammography was calculated using
      computerized billing records. Prior to the intervention, the proportion of visits
      in which women were up-to-date was 68% (95% confidence interval [CI] 63%, 73%) in
      the intervention clinic and 66% (95% CI 61%, 71%) in each of the control clinics.
      At the end of the evaluation, there was an absolute increase of 9% (95% CI 2%,
      16%) in the intervention clinic, and a difference of 1% (95% CI -5%, 7%) in one
      of the control clinics and -2% (95% CI -3%, 5%) in the other. In the intervention
      clinic, the proportion of visits in which women were up-to-date with mammography
      increased over time and was consistent with a linear trend (p = .004).
      CONCLUSIONS: Redesigning clinic processes to make offering of mammography by
      medical assistants and licensed practical nurses a routine part of the clinic
      encounter can lead to mammography rates that are superior to those seen in
      physicians' usual practice, even when screening levels are already fairly high.
      Physicians need not be considered the sole, or even the primary, member of the
      health care team who can effectively deliver some preventive health measures.

PMID- 9192254
TI  - Tube feeding preferences among nursing home residents.
AB  - OBJECTIVE: To determine the preferences of nursing home residents regarding the
      use of tube feedings and to characterize the clinical, functional, and
      psychosocial factors that are associated with preferences. DESIGN: In-person
      survey. SETTING: Forty-nine randomly selected nursing homes.
      PATIENTS/PARTICIPANTS: Three hundred seventy-nine randomly selected, decisionally
      capable, nursing home residents. MAIN RESULTS: Thirty-three percent of
      participants would prefer tube feedings if no longer able to eat because of
      permanent brain damage. Factors positively associated with preferences for tube
      feedings include male gender. African-American race, never having discussed
      treatment preferences with family members or health care providers, never having
      signed an advance directive, and believing that tube feeding preferences will be
      respected by the nursing home staff. Twenty-five percent of the participants
      changed from preferring tube feedings to not preferring tube feedings on learning
      that physical restraints are sometimes applied during the tube feeding process.
      CONCLUSIONS: Demographic and social factors are associated with preferences for
      tube feedings. The provision of information about the potential use of physical
      restraint altered a proportion of nursing home residents' treatment preferences.

PMID- 9192256
TI  - Chronic venous insufficiency and venous ulceration.
AB  - OBJECTIVE: To review and summarize the literature on the normal venous
      circulation of the leg, and the epidemiology, pathophysiology, and treatment of
      chronic venous insufficiency (CVI). DATA SOURCES: English-language articles
      identified through a MEDLINE search (1966-1996) using the terms venous
      insufficiency or varicose ulcer and epidemiology, pathophysiology, diagnosis, and
      clinical trial (pt), and selected cross-references. STUDY SELECTION: Articles on
      epidemiology, pathophysiology, and treatment of CVI. Randomized, controlled
      studies were specifically sought for treatment efficacy. DATA EXTRACTION: Data
      were manually extracted from selected studies and reviews: emphasis was placed on
      information relevant to the general internist. DATA SYNTHESIS: Chronic venous
      insufficiency is a common primary care problem associated with significant
      morbidity and health care costs. The clinical spectrum of disease ranges from
      minor cosmetic concerns to severe fibrosing panniculitis and ulceration. Duplex
      Doppler ultrasonography may be the single best test to rule out deep venous
      thrombosis and other entities that can mimic CVI. Leg elevation and compression
      stockings are effective treatments for CVI; recalcitrant cases may require
      intermittent pneumatic compression. Topical antiseptics, antibiotics, enzymes, or
      growth factors offer no clear advantages in ulcer healing. Ulcer dressings remain
      a matter of convenience, cost, and physician judgment. The role of surgery in CVI
      appears to be limited. CONCLUSIONS: Chronic venous insufficiency is a
      recalcitrant, recurrent medical problem. This condition can be managed by primary
      care physicians with relatively inexpensive treatment modalities in association
      with lifestyle modification.

PMID- 9192257
TI  - The efficacy of selective serotonin reuptake inhibitors for the management of
      chronic pain.
AB  - OBJECTIVE: To assess the effectiveness of selective serotonin reuptake inhibitors
      (SSRIs) in the management of chronic pain. METHODS: Randomized, controlled trials
      of SSRIs in the management of chronic pain were identified by searching MEDLINE
      from 1966 to 1997 and by contacting the manufacturers of SSRIs available in the
      United States. MAIN RESULTS: Nineteen studies were identified, including 10 on
      the treatment of headache, 3 on diabetic neuropathy, 3 on fibromyalgia, and 3 on
      mixed-chronic pain. SSRIs were consistently helpful for mixed-chronic pain.
      Results were conflicting for migraine headache, tension headache, diabetic
      neuropathy, and fibromyalgia. CONCLUSIONS: SSRIs appear to be beneficial for
      mixed-chronic pain. It is unclear, from the available evidence, whether SSRIs are
      beneficial for migraine headaches, tension headaches, diabetic neuropathy, or
      fibromyalgia. For those patients it may be reasonable to reserve SSRIs for those
      who fall to respond to other medications or who are intolerant of their side
      effects.

PMID- 9192258
TI  - Internal medicine residency training and outcomes.
AB  - OBJECTIVE: To review the impact of the clinical education of internal medicine
      residents on patients' outcomes. DATA SOURCES AND STUDY SELECTION: English
      language studies of the relation between internal medicine housestaff training
      and patients' outcomes were systematically identified by a MEDLINE search and
      from bibliographies and reference lists of recently published articles. MAIN
      RESULTS: We hypothesized that the primary impact of internal medicine residency
      training on patients' outcomes would be the result of: (1) the inexperience of
      the residents; (2) the heavy workload these inexperienced residents are expected
      to manage: or (3) some structural feature of the internal medicine teaching
      services, such as the discontinuity of patient care inherent in night float
      systems and the fact that residents rotate to different services each month. We
      also hypothesized that residents may in may ways provide superior care, and many
      actually improve certain patient outcomes. Housestaff inexperience, workload, and
      structural features that promote discontinuity have been shown to affect
      especially outcomes of resource utilization, length of stay, and patient
      satisfaction. No study has demonstrated that internal medicine residents
      contribute to excess patient morbidity or mortality. However, the published
      studies in this area are for the most part retrospective and were conducted 10 to
      15 years ago. The full extent of the untoward (or the beneficial) effects of
      internal medicine residency training on patients' outcomes is unknown.
      CONCLUSIONS: Multisite, prospective studies would remedy the deficiencies in the
      published research in this area and would yield the most valid insight into the
      range and extent of the effects of housestaff training on patients' outcomes. In
      the absence of such studies and in a rapidly changing managed care environment,
      academic medical centers and departments of medicine need to be aware of those
      aspects of the clinical education of residents that are most likely to affect
      patients' outcomes.

PMID- 9192260
TI  - Costly outcomes of education--another case of nature versus nurture.

PMID- 9192259
TI  - How and when should physicians discuss clinical decisions with patients?

PMID- 9192261
TI  - Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall
      syndrome.
AB  - Pallister-Hall syndrome is a human developmental disorder that is inherited in an
      autosomal dominant pattern. The phenotypic features of the syndrome include
      hypothalamic hamartoma, polydactyly, imperforate anus, laryngeal clefting, and
      other anomalies. Here we describe the clinical characterisation of a family with
      22 affected members and the genetic mapping of the corresponding locus. Clinical,
      radiographic, and endoscopic evaluations showed that this disorder is a fully
      penetrant trait with variable expressivity and low morbidity. By analysing 60
      subjects in two families using anonymous STRP markers, we have established
      linkage to 7p13 by two point analysis with D7S691 resulting in a lod score of 7.0
      at theta = 0, near the GLI3 locus. Deletions and translocations in GLI3 are
      associated with the Greig cephalopolysyndactyly syndrome. Although Greig
      cephalopolysyndactyly syndrome has some phenotypic overlap with Pallister-Hall
      syndrome, these two disorders are clinically distinct. The colocalisation of loci
      for these distinct phenotypes led us to analyse GLI3 for mutations in patients
      with Pallister-Hall syndrome. We have previously shown GLI3 mutations in two
      other small, moderately affected families with Pallister-Hall syndrome. The
      linkage data reported here suggest that these larger, mildly affected families
      may also have mutations in GLI3.

PMID- 9192262
TI  - The incidence of deafness is non-randomly distributed among families segregating
      for Waardenburg syndrome type 1 (WS1).
AB  - Waardenburg syndrome (WS) is caused by autosomal dominant mutations, and is
      characterised by pigmentary anomalies and various defects of neural crest derived
      tissues. It accounts for over 2% of congenital deafness. WS shows high
      variability in expressivity within families and differences in penetrance of
      clinical traits between families. While mutations in the gene PAX3 seem to be
      responsible for most, if not all, WS type 1, it is still not clear what accounts
      for the reduced penetrance of deafness. Stochastic events during development may
      be the factors that determine whether a person with a PAX3 mutation will be
      congenitally deaf or not. Alternatively, genetic background or non-random
      environmental factors or both may be significant. We compared the likelihoods for
      deafness in affected subjects from 24 families with reported PAX3 mutations, and
      in seven of the families originally described by Waardenburg. We found evidence
      that stochastic variation alone does not explain the differences in penetrances
      of deafness among WS families. Our analyses suggest that genetic background in
      combination with certain PAX3 alleles may be important factors in the aetiology
      of deafness in WS.

PMID- 9192263
TI  - Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of
      37 children and adolescents with VCFS.
AB  - We report data on a group of 37 VCFS patients with specific reference to their
      intelligence, behaviour, and social competence. Fifty five percent of the
      children had a borderline to normal IQ. Mental retardation (defined as IQ < 70 or
      > -2 SD below the mean) was found in 45%. In the majority, the mental retardation
      was mild (38%) and only two patients had moderate mental retardation. Severe
      mental retardation seems to be rare in VCFS. The present study shows also that
      the incidence of mental retardation is much higher in the familial than the de
      novo group. Intelligence is not correlated with the presence or absence of a
      heart defect. Significantly higher verbal IQs than performance IQs (probably
      related to deficits in visuospatial-perceptual functioning) were found. Problems
      in social-emotional functioning and attention were also found. Further
      longitudinal studies are necessary to provide an accurate prognosis and
      appropriate intervention for VCFS children.

PMID- 9192264
TI  - The uptake and acceptability to patients of cystic fibrosis carrier testing
      offered in pregnancy by the GP.
AB  - OBJECTIVE: To determine the uptake and acceptability of cystic fibrosis (CF)
      carrier testing when offered to women at the first antenatal booking appointment
      by their general practitioner. SETTING: Eight-general practices in the north west
      region with a combined patient list size of 42000. DESIGN: Offer of carrier
      screening at first antenatal booking appointment to pregnant women below 14
      weeks' gestation; women accepting were alternately allocated to either couple
      testing (with full disclosure) or stepwise testing: SUBJECTS: Six hundred and
      twenty three women were offered CF carrier testing. MAIN OUTCOME MEASURES: (1)
      Acceptance of the offer of CF carrier testing. (2) Acceptability of the test to
      women following screening, evaluated through (i) postal questionnaire, (ii)
      semistructured interview. RESULTS: Five hundred and twenty-nine (84.9%) women
      accepted the test; the level of uptake varied across the eight practices (range
      11-99%). In 26/249 (10%) couple tests no paternal sample was provided. When asked
      what had influenced their decision to be tested, 59/377 (16%) women did not refer
      to CF in their answers and six (2%) said that they did not feel they could refuse
      the test. After receiving their results, 368/379 (97%) women felt that they had
      made the right decision to be tested, but two carriers and three non-carriers had
      felt unhappy about testing. Couple testing with full disclosure was associated
      with lower anxiety levels two weeks after receiving the result for the pregnancy
      than stepwise testing and 82/278 (29%) non-carriers believed that they had no
      residual risk in relation to CF. CONCLUSIONS: The response from women accepting
      CF carrier testing was largely positive but a minority of women expressed concern
      about the test and the way it was offered and a substantial proportion of women
      were falsely reassured by their "negative" result. Higher levels of acceptance
      tended to occur in the practices which offered the test there and then rather
      than giving couples more time to decide about testing. Some women appeared to
      have accepted the test because of a belief in the importance of testing in
      pregnancy rather than because of the disease in question.

PMID- 9192265
TI  - Arch fingerprints, hypotonia, and areflexia associated with X linked mental
      retardation.
AB  - A syndrome with distinctive facies, poor muscle tone, absent deep tendon
      reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild
      moderate mental retardation has occurred in four males in two generations of a
      white family of European ancestry. The facies are characterised by square
      configuration, tented upper lip, and thickening of the helices, upper eyelids,
      and alae nasi. At birth and at maturity, growth (head circumference, height,
      weight) of affected males is comparable to or greater than unaffected male sibs.
      Moderate impairment of cognitive function was documented (IQ scores between 40
      51). Carriers show no heterozygote manifestations. This X linked condition
      appears to be different from other syndromes with mental retardation, although
      there are certain similarities with the alpha thalassaemia-mental retardation
      syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in
      Xq13 and Xq21 respectively.

PMID- 9192266
TI  - Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal
      recessive muscular dystrophy (LGMD2D).
AB  - Sarcoglycanopathies are a genetically heterogeneous group of autosomal recessive
      muscular dystrophies in which the primary defect may reside in any of the genes
      coding for the different partners of the sarcolemmal sarcoglycan (SG) complex:
      the alpha-SG (LGMD2D at 17q21.2), the beta-SG (LGMD2E at 4q12), the gamma-SG
      (LGMD2C at 13q12), and the delta-SG (LGMD2F at 5q33). We report a series of 20
      new unrelated families with 14 different mutations in the alpha-SG gene. Along
      with the mutations that we previously reported this brings our cohort of patients
      with alpha-sarcoglycanopathy to a total of 31 unrelated patients, carrying 25
      different mutations. The missense mutations reside in the extracellular domain of
      the protein. Five of 15 missense mutations, carried by unrelated subjects on
      different haplotype backgrounds and of widespread geographical origins, account
      for 58% of the mutated chromosomes, with a striking prevalence of the R77C
      substitution (32%). The severity of the disease varies strikingly and correlates
      at least in part with the amount of residual protein and the type of mutation.
      The recurrent R284C substitution is associated with a benign disease course.

PMID- 9192267
TI  - Improved molecular diagnosis of facioscapulohumeral muscular dystrophy (FSHD):
      validation of the differential double digestion for FSHD.
AB  - A major advance in the molecular diagnosis of facioscapulohumeral muscular
      dystrophy is the recently reported elimination of confounding DNA fragments
      arising from homologous sequences located at 10q26. In order to evaluate the
      specificity and sensitivity of this important diagnostic test, we have compared a
      group of 130 patients fulfilling the diagnostic criteria for FSHD with 200
      control subjects not known to have an increased risk of having an FSHD mutation.
      Among the FSHD cases the smallest BlnI/EcoRI fragment sizes ranged from 10 to >
      48 kb with 94.6% (95% CI 89.2-97.8%) of cases having fragment sizes of 34 kb or
      less. Among the 400 chromosomes from controls the smallest BlnI/EcoRI fragment
      observed with the EcoRI/BlnI double restriction enzyme digest was 38 kb +/- 2 kb,
      suggesting a test specificity at a fragment size < 34 kb of or very near to 100%
      (lower 95% CI 98.2%). Test sensitivity at < 34 kb is estimated at 94.6% (95% CI
      89.2-97.8%), all outliers having fragments > 38 kb. The Southern blot analysis
      with DNA probe p13E-11 has created a valuable molecular diagnostic test for FSHD.

PMID- 9192268
TI  - Large scale deletions in the GPC3 gene may account for a minority of cases of
      Simpson-Golabi-Behmel syndrome.
AB  - AIMS OF THE STUDY: To identify the proportion and type of deletions present in
      the glypican 3 (GPC3) gene in a group of patients with Simpson-Golabi-Behmel
      syndrome (SGBS). SUBJECTS AND METHODS: PCR analysis using primer pairs which
      amplify fragments from each of the eight exons of the GPC3 gene was carried out
      in a series of 18 families with SGBS (approximately half of reported cases).
      RESULTS: Deletions were detected in only five families (one reported previously).
      We found deletions in all exons of the gene except exon 3. CONCLUSIONS: Our
      results suggest that large scale deletions may be less common in SGBS than was
      originally thought. One patient, with an exon 4 and 5 deletion, lacked the
      characteristic facial dysmorphic features. This raises the possibility of
      involvement of GPC3 gene defects in a wider range of overgrowth disorders.

PMID- 9192269
TI  - Identification of novel Bruton's tyrosine kinase mutations in 10 unrelated
      subjects with X linked agammaglobulinaemia.
AB  - Mutations of the Bruton's tyrosine kinase (Btk) gene cause X linked
      agammaglobulinaemia (XLA). This inherited immunodeficiency disease causes an
      arrest in B cell differentiation of pre-B cells to mature B cells. In this study
      we report the characterisation of mutations in the Btk gene in 10 unrelated XLA
      families. The screening approach we used was based on reverse transcriptase PCR
      and direct cycle sequencing of the amplified products followed by analysis of the
      observed mutations at the level of genomic DNA. The single strand confirmation
      polymorphism (SSCP) technique was used for assessment of the carriers in some of
      these families. Various mutations throughout the coding gene were observed,
      including missense and nonsense mutations, a deletion, and several splicing
      defects. None of the mutations except one has been previously described. There
      were three point mutations resulting in a single amino acid substitution. One of
      these missense mutations was observed in a conserved region of the PH domain, the
      other two were found in the src homology domain 2 that is involved in
      phosphotyrosyl peptide binding. Two mutations were single base pair substitutions
      resulting in premature stop codons. In four patients abnormal Btk transcripts
      were found that were the result of aberrant splicing. One small deletion was
      observed causing a frameshift and a secondary premature termination signal.
      Characterisation of the mutations responsible for XLA allowed us to diagnose the
      disease conclusively and identify the phenotypically normal female carriers.

PMID- 9192270
TI  - Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT
      gene.
AB  - Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inborn error
      of glyoxylate metabolism caused by deficiency of the hepatic peroxisomal enzyme
      alanine:glyoxylate aminotransferase. This enzyme is encoded by the AGXT gene on
      chromosome 2q37.3. DNA samples from 79 PH1 patients were studied using single
      strand conformation polymorphism analysis to detect sequence variants, which were
      then characterised by direct sequencing and confirmed by restriction enzyme
      digestion. Four novel mutations were identified in exon 7 of AGXT: a point
      mutation T853C, which leads to a predicted Ile244Thr amino acid substitution,
      occurred in nine patients. Two other mutations in adjacent nucleotides, C819T and
      G820A, mutated the same codon at residue 233 from arginine to cysteine and
      histidine, respectively. The fourth mutation, G860A, introduced a stop codon at
      amino acid residue 246. Enzyme studies in these patients showed that AGT
      catalytic activity was either very low or absent and that little or no
      immunoreactive protein was present. Together with a new polymorphism in exon 11
      (C1342A) these findings underline the genetic heterogeneity of the AGXT gene. The
      novel mutation T853C is the second most common mutation found to date with an
      allelic frequency of 9% and will therefore be of clinical importance for the
      diagnosis of PH1.

PMID- 9192271
TI  - Metachromatic leucodystrophy in three families from Nova Scotia, Canada: a
      recurring mutation in the arylsulphatase A gene.
AB  - Metachromatic leucodystrophy (MLD) is a lysosomal storage disease resulting from
      a deficiency of arylsulphatase A. We have identified a child with infantile onset
      MLD who is homozygous for an A212V mutation, a mutation previously reported but
      not further characterised. We have introduced this mutation into an
      arylsulphatase A expression vector by site directed mutagenesis. Transient
      expression of this mutant plasmid in COS cells yields very low levels of
      arylsulphatase A activity consistent with the patient's phenotype. The
      arylsulphatase A pseudodeficiency also segregates in this family causing
      difficulty in interpreting enzyme levels in the absence of DNA data. Two other
      patients from the same province, also carrying the A212V allele, have juvenile
      and adult onset MLD and are heterozygous for P426L ("A" allele) and I179S alleles
      respectively, known late onset alleles.

PMID- 9192272
TI  - Pure hereditary spastic paraplegia.

PMID- 9192273
TI  - Linkage mapping of a large Colombian family segregating for X linked
      retinoschisis: refinement of the chromosomal location.
AB  - Juvenile X linked retinoschisis (RS) is a bilateral vitreoretinal dystrophy that
      develops early in life. Previous linkage studies have localised the RS gene to
      Xp22.1-p22.3 between DXS207 and AFM 291Wf5, which represents a genetic distance
      of approximately 3.7 cM. In an effort to facilitate the eventual cloning of the
      RS gene, we have analysed a large Colombian family, using 10 microsatellite
      markers that have been mapped to the region Xp22.1-p22.3. A total of 93 members,
      including 19 affected and eight unaffected males, two affected females, and six
      obligate carrier females were analysed. Close linkage was observed between the
      disease locus and DXS999 (Zmax = 2.27, theta max = 0.05), DXS987 (Zmax = 2.61,
      theta max = 0.1), DXS443 (Zmax = 4.23, theta max = 0.1), and DXS274 (Zmax = 3.49,
      theta max = 0.05) markers. Recombination with the RS locus was found for all
      marker loci except DXS197, DXS43, and DXS1195. These results place the RS locus
      within an interval of approximately 2 cM between the flanking markers DXS1053 and
      DXS999, approximately 1.7 cM closer than the previously reported boundary. The
      results also further confirm the lack of genetic heterogeneity of RS.

PMID- 9192274
TI  - SMN gene analysis of the spinal form of Charcot-Marie-Tooth disease.
AB  - The spinal form of Charcot-Marie-Tooth disease (spinal CMT) is a rare genetic
      disorder of the peripheral nervous system, the genetic basis of which remains
      unknown. To test the hypothesis that a defect of survival motor neuron (SMN), the
      determining gene for spinal muscular atrophy (SMA), would result in spinal CMT,
      18 unrelated spinal CMT patients were studied. Nine of them were sporadic cases
      and the other nine belonged to unrelated autosomal dominant pedigrees. None of
      the 18 patients showed deletions involving SMN exons 7 or 8, the most frequent
      gene alteration found in SMA. In addition, haplotype analysis in two large
      autosomal dominant pedigrees showed that the 5q13 locus was not segregating with
      the spinal CMT locus. Therefore, neither the sporadic nor the familial cases of
      spinal CMT are associated with a SMN gene deletion, nor are the familial cases
      linked to the 5q13 region, indicating that this neuropathy is genetically
      different from SMA.

PMID- 9192275
TI  - Molecular analysis of the human vitamin D binding protein (group specific
      component, Gc) in tuberous sclerosis complex (TSC).
AB  - Group specific component (Gc) is an abundant plasma protein whose functional role
      is not clearly established. Gc protein is synthesised in the liver and is known
      to bind vitamin D, vitamin D metabolites, and G actin; Gc protein is also
      implicated in macrophage activation. Several polymorphic electrophoretic variants
      of Gc protein are found in all human populations; the most common alleles are Gc
      1f, Gc-1s, and Gc-2. In previous studies, Gc allele frequencies, determined using
      isoelectric focusing or immunofixation or both, were significantly different in
      patients with tuberous sclerosis complex (TSC) from matched controls, with an
      excess of Gc-2 in patients. Linkage association between Gc and TSC is unlikely
      since the Gc locus maps to chromosome 4q12, whereas the two common forms of TSC
      map to 9q34 and 16p13.1, respectively. However, a direct cause and effect
      relationship between Gc protein and TSC symptoms is possible. To investigate
      further the relationship between the Gc locus and TSC, two Gc restriction site
      polymorphisms, HaeIII and StyI, were typed in 43 unrelated white subjects with
      TSC. The frequencies of the restriction site polymorphisms in the TSC patients
      did not differ from those in control populations. Therefore a direct association
      between Gc type and TSC is unlikely. The previously reported association was
      either spurious or the result of typing errors in plasma from subjects with
      underlying abnormalities in plasma proteins.

PMID- 9192276
TI  - Mosaicism for trisomy 3q arising from an unbalanced, de novo t(3;15).
AB  - We report on a 2 1/2 year old girl who is dysmorphic, developmentally delayed,
      and mosaic for an unbalanced, de novo translocation between chromosomes 3 and 15.
      The karyotype from peripheral blood lymphocytes is 46,XX (50) and the karyotype
      from skin fibroblasts is 46,XX (28)/46,XX,der(15)t(3;15)(q11;p11) (23). The
      mechanism for the generation of this unbalanced, de novo translocation is
      discussed.

PMID- 9192277
TI  - Delineation of 14q32.3 deletion syndrome.
AB  - A patient with a 14q32.3 terminal band deletion and cat cry is reported. Review
      of four other 14q32.3 deletion cases suggests the possible presence of a
      recognisable 14q32.3 terminal deletion syndrome, which is characterised by (1)
      apparently postnatal onset of small head size in comparison to body size, (2)
      high forehead with lateral hypertrichosis, (3) epicanthic folds, (4) broad nasal
      bridge, (5) high arched palate, (6) single palmar crease, and (7) mild to
      moderate developmental delay. Although none of the above seven features in unique
      to this syndrome, and indeed are quite common in other chromosomal disorders or
      genetic syndromes, patients with a terminal 14q32.3 deletion do show a
      recognisable facial gestalt. Interestingly, unlike ring chromosome 14, the
      14q32.3 terminal deletion has rarely been reported, possibly because it is harder
      to detect, and an optimal chromosome preparation is required for its
      identification.

PMID- 9192278
TI  - Lethal femoral-facial syndrome: a case with unusual manifestations.
AB  - The femoral-facial syndrome is a very rare syndrome of uncertain inheritance
      comprising hypoplastic femora, microretrognathia, and a peculiar facies. We
      report an additional observation detected by ultrasound at 25 weeks and diagnosed
      at birth. In addition to the malformations usually described in this syndrome,
      there were heterotopias of the brain, partial agenesis of the corpus callosum,
      bilobed lungs, intestinal malrotation, and vertebral segmentation defects.

PMID- 9192279
TI  - A maternally transmitted lethal neonatal progeroid syndrome with prominent
      genitourinary and gastrointestinal features.
AB  - Twin brothers and their maternal uncle with a previously undescribed neonatal
      progeroid syndrome are presented. In addition to progeroid features, they had
      pseudo-obstruction of the urinary and gastrointestinal tracts, severe
      leucocytosis, liver dysfunction, and low complex III and IV in muscle but not in
      liver. Previously described neonatal progeroid syndromes and syndromes featuring
      pseudo-obstruction are discussed. The two most likely aetiological mechanisms are
      an X linked single gene disorder or a mitochondrial disorder. The evidence for
      these possibilities is presented.

PMID- 9192280
TI  - Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia.
AB  - A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR)
      gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR
      activity and associated with modestly increased plasma homocysteine
      concentrations. Since underlying maternal vascular disease increases the risk of
      pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would
      have an increased T677 allele frequency compared with controls. The MTHFR
      genotypes were determined in 67 pre-eclampsia patients, 98 normal pregnant women,
      and 260 healthy adults by the PCR/RFLP method. The T677 allele and the genotype
      homozygous for the T677 allele were significantly increased in the pre-eclamptic
      group compared with the controls (p < 0.02 and p < 0.004, respectively). The data
      indicate that the T677 variant of the MTHFR gene is one of the genetic risk
      factors for pre-eclampsia.

PMID- 9192281
TI  - Presynaptic terminals in hyaline cells of normal and overstimulated chick inner
      ears.
AB  - Hyaline cells are non-sensory epithelial cells of the vibrating part of the
      basilar membrane of chicks; they receive an extensive efferent innervation.
      Although these anatomical features suggest roles in auditory transduction, very
      little is known about the function of these cells. One possible way to understand
      function is by lesion experiments. We used synapsin-specific antibodies to study
      changes that occur in the pattern of efferent innervation in hyaline cells after
      lesion of the sensory epithelium induced by acoustic overstimulation. We found
      only small changes in hyaline cells after such trauma. These included a small
      increase in size and a small decrease in density of nerve terminals on hyaline
      cells. This suggests that hyaline cells and their nerve terminals are less
      susceptible to acoustic trauma than hair cells. Using neurofilament-specific
      antibodies we found little or no trauma-induced change in the density of nerve
      fibres that cross the basilar papilla and reach the hyaline cell region. This
      finding suggested that trauma to the hair cells does not necessarily lead to
      changes in the efferent fibres that cross the papilla and extend into the hyaline
      cell region. Using the trauma and the morphological parameters studied here, it
      appears that a moderate lesion in the hair cell region in the avian inner ear
      does not influence the hyaline cells or their innervation.

PMID- 9192282
TI  - Ontogenetic development of diffusional restriction to protein at the pial surface
      of the rat brain: an electron microscopical study.
AB  - Blood-brain, blood-CSF and ventricular CSF-brain barriers to protein are present
      very early in brain development. In order to determine whether the outer pial
      surface of the brain also restricts free penetration of macromolecules, the dorso
      lateral part of the sensorimotor cortex from rats at embryonic day 12 (E12), 14,
      16, and 18, the day of birth (P0), and adult rat, was studied by electron
      microscopical techniques. Potassium ferrocyanide, Ruthenium Red and immunogold
      labelling of endogenous albumin were used to investigate junctional structures
      and the sites of restriction to albumin diffusion. At E12, large fenestrated
      sinusoids were present in the pia-arachnoid and the brain surface was formed by
      an incomplete layer of neuroepithelial and presumptive radial glial end feet, but
      capillaries in the pia-arachnoid showed no fenestrations at E14 or later. From
      E14, we observed the progressive appearance of distinct junctional structures
      between the glial end feet which, to our knowledge, have not been described
      before. Analysis of albumin distribution from E16 to P0 suggests that the
      junctions may contribute to restriction of diffusion between the subarachnoid
      space and the brain extracellular fluid. The restriction to the penetration of
      protein at both the pial and the ependymal surfaces may ensure the isolation of
      the neural environment during a critical phase in development of the nervous
      system. The changes in the structure of the junctions between E12 and P0 suggests
      a transitional series of embryonic junctional types, which eventually give way to
      the mature junctions of the adult. Parallels between the embryonic glial
      junctions and junctions described in adult invertebrate brain, suggest some
      interesting parallels in junctional development in phylogeny and ontogeny.

PMID- 9192283
TI  - The regional distribution of myelin oligodendrocyte glycoprotein (MOG) in the
      developing rat CNS: an in vivo immunohistochemical study.
AB  - Using an immunohistochemical approach we have characterized the in vivo
      developmental distribution of myelin oligodendrocyte glycoprotein within the rat
      CNS. Myelin oligodendrocyte glycoprotein expression emerged in a non-uniform
      manner during the first 3 postnatal weeks. Although it was absent throughout the
      CNS of the newborn rat at postnatal day 0(P0), it had appeared in the spinal cord
      and brainstem by P7. The forebrain and cerebellum remained devoid of
      immunoreactivity until after P14. Myelin oligodendrocyte glycoprotein emerged at
      different times within the closely associated fasciculi of the dorsal funiculus.
      It appeared in the fasciculus cuneatus during the first postnatal week and in the
      fasciculus gracilis and corticospinal tracts during weeks 2 and 3 respectively.
      Myelin oligodendrocyte glycoprotein expression developed along a caudo-rostral
      gradient from spinal cord to forebrain and along an antero-posterior gradient
      within the CNS in general. The relationship between the onset of myelin
      oligodendrocyte glycoprotein expression and myelinogenesis was also investigated.
      In most regions, myelin oligodendrocyte glycoprotein expression lagged behind the
      initial appearance of myelin basic protein and Luxol Fast Blue-stained myelin by
      at least 1 week. These observations support the idea that myelin oligodendrocyte
      glycoprotein is the latest myelin protein to appear in development, only being
      expressed during the final stages of oligodendrocyte differentiation.
      Furthermore, the pattern of staggered expression within the dorsal columns
      indicates that localized, region-specific interactions may comprise a key element
      in the control of the terminal phases of oligodendrocyte differentiation.

PMID- 9192284
TI  - Calcitonin gene-related peptide and alpha-CGRP mRNA expression in cranial
      motoneurons after hypoglossal nerve injury during postnatal development.
AB  - Changes in calcitonin gene-related peptide (CGRP) immunoreactivity and alpha-CGRP
      mRNA expression were determined in the hypoglossal nucleus after the nerve was
      crushed or transected in rats at 10, 14 and 21 days postnatal. alpha-CGRP mRNA
      expression was determined in normal, noninjured, hypoglossal nuclei at the three
      ages and after both injuries in 10 and 21 days postnatal rats. Reinnervation and
      neuronal survival were assayed. Although the three age groups expressed
      comparable levels of alpha-CGRP mRNA and its peptide in intact, hypoglossal
      nuclei, axonal injury produced age-dependent alterations in alpha-CGRP mRNA and
      CGRP. In the 21 days postnatal rats, changes in alpha-CGRP mRNA and peptide
      mimicked those reported in adult motoneurons after the same injuries. CGRP was
      elevated until reinnervation after nerve crush, whereas biphasic elevations
      occurred after nerve transection. In 21 days postnatal rats, increases in alpha
      CGRP mRNA preceded elevations of the peptide but a greater increase resulted
      initially after nerve transection. An upregulation of alpha-CGRP mRNA also
      developed initially after both injuries in 10 days postnatal rats but subsequent
      elevations of alpha-CGRP mRNA did not materialize. In contrast, CGRP
      immunoreactivity did not increase after either injury in 10 days postnatal rats
      and, in fact decreased. Levels of CGRP immunoreactivity did not differ from
      normal amounts after either nerve injury in 14 days postnatal rats. Substantial
      neuronal cell loss occurred after each injury in 10 and 14 days postnatal rats
      but was not found in 21 days postnatal rats. Tongue reinnervation by surviving
      motoneurons was established after all injury paradigms except 10 days postnatal
      transection. The current findings demonstrate an age-dependent correlation
      between injury-induced expression of CGRP and hypoglossal motoneuron survival.

PMID- 9192285
TI  - Expression of the dm-20 isoform of the plp gene in olfactory nerve ensheathing
      cells: evidence from developmental studies.
AB  - The olfactory bulb is a specialized area of the CNS with well-defined areas
      containing both myelinated, and non-myelinated axons. The presence of plp gene
      transcripts has been demonstrated previously in the olfactory bulb, but no
      detailed description of plp gene activity in this complex area of the CNS is
      available. In this study we describe the developmental expression of the two plp
      gene isoforms, plp and dm-20, and their products in the mouse olfactory bulb. plp
      gene activity was present in the non-myelinated olfactory nerve layer of the bulb
      from E14 through to adult ages. Expression in the deeper layers of the bulb,
      associated with myelination of the second order axons, was apparent from P10
      onwards. dm-20 was the predominant isoform expressed at the transcript level in
      the olfactory nerve layer and was the only isoprotein demonstrable by
      immunostaining. This expression was associated with the resident glial cell of
      the non-myelinated olfactory nerve layer, the olfactory nerve ensheathing cell.
      Selective expression of the DM-20 isoprotein in the non-myelin forming olfactory
      nerve ensheathing cells implies a role for DM-20 other than as a structural
      myelin protein. Further study of this specialized glial cell may prove useful in
      elucidating the specific functions(s) of the DM-20 isoprotein.

PMID- 9192286
TI  - Use of a rat Y chromosome probe to determine the long-term survival of glial
      cells transplanted into areas of CNS demyelination.
AB  - A lack of suitable markers for cells which undergo division following
      transplantation has hindered studies assessing the long-term survival of glial
      cell grafts in the CNS. A probe specific to the rat Y chromosome was used to
      identify male glial cells grafted into an area of ethidium bromide-induced
      demyelination in syngeneic adult female rat spinal cord 4 weeks, 6 months and 12
      months post-transplantation. At all time points there was extensive
      oligodendrocyte remyelination of transplanted lesions, and graft-derived cells
      were present within the lesion up to 12 months post-transplantation. In order to
      demonstrate graft-derived oligodendrocytes in the remyelinated region at 6 and 12
      months, double-labelling studies were performed using the oligodendrocyte
      specific antibodies carbonic anhydrase II or phosphatidyl ethanolamine-binding
      protein in combination with the Y chromosome probe. It was found that the
      majority of oligodendrocytes in the transplanted region were graft-derived. Graft
      mediated remyelination was associated with a reduction in myelin sheath thickness
      and increase in nodal frequency similar to that observed in spontaneous
      remyelination, suggesting that, like axons remyelinated spontaneously, axons
      remyelinated by grafted cells will be capable of secure conduction. An alteration
      in the immunoreactivity of oligodendrocytes from carbonic anhydrase II-negative
      in the unlesioned dorsal funiculus to carbonic anhydrase II-positive in the
      remyelinated dorsal funiculus was considered to reflect a reduction in the amount
      of myelin supported by each oligodendrocyte, leading to the proposal that
      carbonic anhydrase II immunoreactivity may provide a means of identifying areas
      of remyelination in normally carbonic anhydrase II-negative white matter tracts.

PMID- 9192288
TI  - Does the reticular thalamic nucleus project to the midbrain?
AB  - In this study, we investigated whether the reticular thalamic nucleus has a
      projection to major centres of the midbrain in rats, rabbits and cats. Various
      tracers (biotinylated dextran, cholera toxin B subunit, fluorescent latex beads)
      were injected either into the midbrain tectum (deep layers of the superior
      colliculus) or tegmentum (midbrain reticular and pedunculopontine nuclei). In
      other experiments, different coloured latex beads (red and green) were injected
      into the deep layers of the superior colliculus and into the midbrain reticular
      nucleus of the same animal (rabbits). Our major finding is that in rats, rabbits
      and cats, there are no retrogradely labelled cells in the reticular thalamic
      nucleus after tracer injections into the above mentioned midbrain centres. In
      rabbits and cats, however, there are retrogradely labelled cells lying close to
      the ventromedial edge of the reticular thalamic nucleus after such injections. We
      show, by means of immunocytochemical double-labelling, that these retrogradely
      labelled cells do not lie in the reticular thalamic nucleus as suggested by
      previous studies, but in the inner small-celled region, a group of small cells
      that forms part of the zona incerta. Although these appears to be no clear
      topography of projection of the inner small-celled region, our tracer double
      labelling experiments show that separate cells in the inner small-celled region
      project to individual centres of the midbrain (i.e., there are very few double
      labelled cells after double injections). In rats, unlike in rabbits and cats,
      there is no clearly defined inner small-celled region and there are no
      retrogradely labelled cells seen along the ventromedial edge of the reticular
      thalamic nucleus. Our results suggest that in rats, rabbits and cats, there is no
      projection of the reticular thalamic nucleus to major centres of the midbrain,
      suggesting that the nucleus may not have a very strong influence on midbrain
      function, as it does on dorsal thalamic function.

PMID- 9192287
TI  - Axonal cytoskeletal changes after non-disruptive axonal injury.
AB  - In animal models of human diffuse axonal injury, axonal swellings leading to
      secondary axotomy occur between 2 and 6 h after injury. But, analysis of
      cytoskeletal changes associated with secondary axotomy has not been undertaken.
      We have carried out a quantitative analysis of cytoskeletal changes in a model of
      diffuse axonal injury 4 h after stretch-injury to adult guinea-pig optic nerves.
      The major site of axonal damage was the middle portion of the nerve. There was a
      statistically significant increase in the proportion of small axons with a
      diameter of 0.5 micron and smaller in which there was compaction of
      neurofilaments. Axons with a diameter greater than 2.0 microns demonstrated an
      increased spacing between cytoskeletal elements throughout the length of the
      nerve. However, in the middle segment of the nerve these larger axons
      demonstrated two different types of response. Either, where periaxonal spaces
      occurred, there was a reduction in axonal calibre, compaction of neurofilaments
      but no change in their number, and a loss of microtubules. Or, where
      intramyelinic spaces occurred there was an increased spacing between
      neurofilaments and microtubules with a significant loss in the number of both.
      Longitudinal sections showed foci of compaction of neurofilaments interspersed
      between regions where axonal structure was apparently normal. Neurofilament
      compaction was correlated with disruption of the axolemma at these foci present
      some hours after injury. We suggest that the time course of these axonal
      cytoskeletal changes after stretch-injury to central axons is shorter than those
      changes documented to occur during Wallerian degeneration.

PMID- 9192289
TI  - Nimodipine maintains in vivo the increase in GFAP and enhances the astroglial
      ensheathment of surviving motoneurons in the rat following permanent target
      deprivation.
AB  - Facial and hypoglossal nerves were resected unilaterally in a total of 108 rats.
      Rats were divided into two groups; one group received standard food pellets
      (placebo), the other received food pellets containing the Ca(2+)-blocking agent
      nimodipine. The expression of glial fibrillary acidic protein was examined in
      paraffin sections of the brainstem using light microscopical immunocytochemistry,
      and the degree of glial process ensheathment of the surviving neuronal perikarya
      in the hypoglossal and facial nuclei quantified on electron micrographs. Up to 28
      days post-axotomy no differences in glial fibrillary acidic protein
      immunoreactivity were observed between placebo and nimodipine-treated animals. By
      42-56 days, glial fibrillary acid protein-immunoreactivity was stronger in the
      nimodipine treated animals and by 112 days, glial fibrillary acid protein
      immunoreactive astrocytes occurred only in nimodipine-treated animals. Thin
      astrocytic processes were seen to ensheath neurons in both placebo and nimodipine
      treated animals. By 28 days post axotomy, lesioned neurons in nimodipine treated
      animals were covered by a mean of 2.6 (hypoglossal) and 2.9 (facial nucleus)
      astrocytic lamellae, compared with 1.7 lamellae in the placebo group. This
      relatively greater ensheathment of hypoglossal and facial neurons was maintained
      up to 112 days post-lesion, but reduced in the placebo-treated group to
      approximately 1.4 lamellae. It is concluded that nimodipine enhances the
      formation of astrocytic lamellae on lesioned neurons and that this process may be
      associated with a protective role for activated astrocytes directed towards
      motoneurons suffering from permanent target-deprivation.

PMID- 9192290
TI  - Morphological plasticity of cultured astrocytes derived from the subfornical
      organ of the adult rat.
AB  - The morphological plasticity of astrocytes from the subfornical organ of the
      adult rat has been examined using an explant culture preparation. Astrocytes
      migrate out of the explant and form a monolayer of amorphous, non-stellate cells.
      This non-stellate form was maintained when cultures were incubated in a HEPES
      buffered salt solution (HBSS) for 50 minutes. The fraction of cells that was
      stellate in these cultures was significantly increased when cultures were
      incubated in HBSS supplemented with forskolin (5 microM; but not 1,9
      dideoxyforskolin) or with nitroprusside (10-100 microM) indicating that elevation
      of intracellular cAMP or cGMP mediates stellation. The stellation responses
      induced by forskolin and by nitroprusside were blocked by inclusion of serum
      (0.5%) or of LY83,583 (10 microM), an inhibitor of soluble guanylate cyclase, in
      the incubation medium. The relevance of the data to neuroglial plasticity in the
      subfornical organ in vivo is discussed.

PMID- 9192291
TI  - Gonadal steroid preservation of central synaptic input to hamster facial
      motoneurons following peripheral axotomy.
AB  - In recent work, we have demonstrated that testosterone propionate accelerates
      recovery from facial nerve injury in the adult male hamster. Central synaptic
      stripping following peripheral motor neuron damage is a well-established
      component of the injury response. Gonadal steroids regulate synaptogenesis in the
      normal nervous system. In this study, we tested the hypothesis that testosterone
      propionate administration at the time of facial nerve transection alters the
      synaptic connectivity of injured facial motoneurons. Adult hamsters were
      subjected to right facial nerve transection at the level of the stylomastoid
      foramen. Half the animals received subcutaneous implants of testosterone
      propionate; the other half were sham implanted. At 5 days postoperative, the
      animals were killed by intracardiac perfusion-fixation, and the control and
      axotomized facial nuclear groups from the brainstems of nonhormone- and
      testosterone propionate-treated animals processed for routine transmission
      electron microscopy. Quantiative analysis of the synaptic ratio (percent somal
      membrane covered by synaptic profiles) and the average length of axosomatic
      synapses was accomplished. The results indicate that axotomy alone resulted in an
      81% reduction in the synaptic ratio and a 26% decrease in the average synaptic
      length of axosomatic synapses. Exposure to testosterone propionate from the time
      of facial nerve transection resulted in only a 48% reduction in the synaptic
      ratio and a 16% decrease in the average synaptic length of axosomatic synapses
      following injury. Thus, testosterone propionate significantly attenuated the
      amount of synaptic stripping that occurred at 5 days postoperative and the
      decrease in average length of the remaining synapses as well. It is concluded
      that gonadal steroids modulate central synaptic plasticity following peripheral
      nerve injury. The results are discussed in light of our recent findings of
      steroidal effects on the central astrocyctic response to facial nerve injury as
      well.

PMID- 9192292
TI  - The temporal progression of the myelination defect in the taiep rat.
AB  - The Sprague Dawley myelin mutant, the taiep rat, demonstrates a defect in CNS
      myelination which worsens with age and which is associated with abnormal
      accumulations of microtubules in oligodendrocytes. Quantitative and qualitative
      electron microscopic studies of myelin development and oligodendrocyte morphology
      were used to describe the temporal development of the defect in this mutant, in
      three regions of the CNS. The results indicate that the time of onset of
      myelination is similar in mutant and control rats, however the amount of myelin
      formed is reduced in the mutant, compared to controls, and there is a loss of
      myelin from the taiep CNS as the animals age. Thus the myelination defect in
      taiep has features of both hypomyelination and demyelination. Oligodendrocyte
      microtubule abnormalities were noted in each region of the taiep CNS at the time
      of onset of myelination. The earliest changes seen were close associations of
      oligodendrocyte microtubules with endoplasmic reticulum, with marked
      accumulations of microtubules filling the cytoplasm of oligodendrocytes from
      older taiep rats. These findings suggest that the microtubule abnormality in the
      taiep mutant inhibits both the initial formation and the long-term maintenance of
      myelin by the oligodendrocyte. In addition, there is also evidence to suggest
      that although the microtubule abnormality is present in oligodendrocytes
      throughout the taiep CNS, it results in a more marked defect in the myelination
      of axons of small diameter.

PMID- 9192293
TI  - Temporal and spatial patterns of expression of p35, a regulatory subunit of
      cyclin-dependent kinase 5, in the nervous system of the mouse.
AB  - The protein p35 is a regulatory subunit of cyclin-dependent kinase 5. It has no
      recognized homology to cyclins but binds to and activates cyclin-dependent kinase
      5 directly in the absence of other protein molecules. Cyclin-dependent kinase 5
      was initially isolated by homology to the key cell cycle regulator cdc2 kinase
      and later identified as a neuronal kinase that phosphorylates histone H1, tau or
      neurofilaments. This kinase is localized in axons of the developing and mature
      nervous system. To understand the role of p35 as a regulator of cyclin-dependent
      kinase 5 activity in the CNS, we examined the pattern of expression of p35 mRNA
      in the nervous system of embryonic, early postnatal and adult mice. In separate
      experiments, we also examined the spatial distribution of cyclin-dependent kinase
      5 mRNA and the activity of cyclin-dependent kinase 5/p35 kinase complex.
      Postmitotic cells express p35 mRNA immediately after they leave the zones of cell
      proliferation. It is also expressed in developing axonal tracts in the brain.
      Cyclin-dependent kinase 5 mRNA is present in postmitotic and in proliferative
      cells throughout the embryonic central nervous system. During early postnatal
      period signal for p35 mRNA declines while that for cyclin-dependent kinase 5 mRNA
      increases throughout the brain. In the adult brain although both p35 and cyclin
      dependent kinase 5 mRNAs are expressed at relatively high levels in certain
      structures associated with the limbic system, considerable differences exist in
      the patterns of their distribution in other parts of the brain. These data
      suggest that the p35/cyclin-dependent kinase 5 complex may be associated with
      early events of neuronal development such as neuronal migration and axonal growth
      while in the limbic system of the mature brain it may be associated with the
      maintenance of neuronal plasticity.

PMID- 9192294
TI  - Putative odour receptors localize in cilia of olfactory receptor cells in rat and
      mouse: a freeze-substitution ultrastructural study.
AB  - Two different polyclonal antibodies were raised to synthetic peptides
      corresponding to distinct putative odour receptors of rat and mouse. Both
      antibodies selectively labelled olfactory cilia as seen with cryofixation and
      immunogold ultrastructural procedures. Regions of the olfactory organ where label
      was detected were consistent with those found at LM levels. Immunopositive cells
      were rare; only up to about 0.4% of these receptor cells were labelled. Despite
      chemical, species, and topographic differences both antibodies behaved
      identically in their ultrastructural labelling patterns. For both antibodies,
      labelling was very specific for olfactory cilia; both bound amply to the thick
      proximal and the thinner and long distal parts of the cilia. Dendritic knobs
      showed little labelling if any. Dendritic receptor cell structures below the
      knobs, supporting cell structures, and respiratory cilia did not immunolabel.
      There were no obvious differences in morphology between labelled and unlabelled
      receptor cells and their cilia. Labelling could be followed up to a distance of
      about 15 microns from the knobs along the distal parts of the cilia. When
      labelled cells were observed, this signal was detectable in two, sometimes three,
      sections taken through these cells while being consistently absent in
      neighbouring cells. This pattern argues strongly for the specificity of the
      labelling. In conclusion, very few receptor cells labelled with the antibodies to
      putative odour receptors. Additionally the olfactory cilia, the cellular regions
      that first encounter odour molecules and that are thought to transduce the
      odorous signal, displayed the most intense labelling with both antibodies.
      Consequently, the results showed these cilia as having many copies of the
      putative receptors. Finally, similar patterns of subcellular labelling were
      displayed in two different species, despite the use of different antibodies.
      Thus, this study provides compelling evidence that the heptahelical putative
      odour receptors localize in the olfactory cilia.

PMID- 9192295
TI  - The cone synapses of cone bipolar cells of primate retina.
AB  - One each of bipolar cell types DB2 and DB4, together with a flat and an
      invaginating midget bipolar cell, were taken from a Golgi-stained rhesus macaque
      retina; then serially sectioned for EM examination of their synapses with cone
      pedicles. The cone input to the dendrites of the DB2 cell was exclusively at
      basal junctions; it had a characteristic distribution. Fifty per cent of the
      basal synapses were with cone pedicle membrane immediately adjacent to the
      dendrite of a bipolar cell invaginating to end opposite the ribbon of a cone
      triad (this, therefore, is called triad-associated). The remainder were one or
      more synapses distant from the triad-associated position (and, therefore, non
      triad associated). The DB4 cell had both basal (predominantly in the triad
      associated position) and ribbon-related synaptic input. But the basal to
      invaginating ratio differed from that of our previously published cell; 56%
      basal, 43% invaginating, as compared with 31% basal and 69% invaginating. Like
      foveal IMB cells the synapses of the mid-peripheral invaginating midget bipolar
      cell were exclusively invaginating; but were about 25% more numerous. The flat
      midget bipolar cell made exclusively basal synapses. These were 2.5 times more
      numerous than those of foveal flat midget bipolar cells, and 3.5 times the number
      of invaginating midget bipolar synapses at equivalent eccentricity. The synapses
      between cones and diffuse and midget bipolar cells are characteristic for each
      particular bipolar cell type, but the details depend on a cell's distance from
      the fovea (eccentricity). A rather constant number of cone pedicle synaptic
      ribbons 38.6 +/- 2.5 (n = 60) was found across mid-peripheral macaque and vervet
      monkey retinae. The smaller mean number for vervet monkey, 27.4 +/- 3.5 (n = 23),
      suggests there can also be generic differences in synaptic detail at cone bipolar
      cell synapses.

PMID- 9192296
TI  - The relationship between developing oligodendrocyte units and maturing axons
      during myelinogenesis in the anterior medullary velum of neonatal rats.
AB  - Myelinogenesis was investigated in whole-mounted anterior medullary vela from
      rats aged postnatal day (P) 10-12, using double immunofluorescence labelling with
      Rip and anti-neurofilament 200 (NF200) antibodies, to identify oligodendrocytes
      and axons, respectively. A number of discrete phases of maturation of
      oligodendrocyte units were recognised. (1) Promyelinating oligodendrocytes co
      expressed Rip and Myelin basic Protein and formed axonal associations, prior to
      ensheathment. (2) Transitional oligodendrocytes contained both ensheathing and
      non-ensheating processes. (3) Myelinating oligodendrocytes were established after
      a period of remodelling (in which non-ensheathing processes were lost), appearing
      as oligodendrocyte unit morphological phenotypes with a definitive number of
      incipient myelin sheaths. (4) Maturation of myelinating oligodendrocytes was
      defined as the establishment of internodal sheath lengths and the redistrubution
      of myelin basic protein from the cell somata and radial processes into the myelin
      sheaths only. Myelination was probably related to the maturational state of the
      axons, since it was initiated when the latter had attained a critical diameter of
      between approximately 0.2 and 0.4 micron, coincident with the expression of
      NF200. Oligodendrocyte differentiation and myelination of the AMV were
      asynchronous and multifocal, and at P10: (1) axons which were destined to be of
      the largest calibre in the adult AMV were already myelinated by early developing
      oligodendrocytes, whilst those which were destined to be the smallest calibre in
      the adult were unmyelinated, but ultimately became ensheathed by late developing
      oligoendrocytes; (2) axons were sequentially ensheathed by early developing
      myelinating oligodendrocytes and late developing promyelinating oligodendrocytes;
      (3) all axons were small calibre; (4) oligodendrocyte units exhibited
      polymorphism. Thus, the development of oligodendrocyte morphological phenotypes
      was not related solely to either the physical dimension of axon calibre at the
      time of ensheathment, nor oligodendrocyte birth dates.

PMID- 9192297
TI  - Diphenylpiperazines enhance regeneration after facial nerve injury.
AB  - Immature rat facial motoneurons are very sensitive to injury with nearly 80%
      dying during the first week after axotomy. This motoneuron death is apoptotic,
      similar to that induced in neurons after tropic factor withdrawal. The
      diphenylpiperazines, flunarizine and cinnarizine, protect dorsal root ganglion
      neurons from death after withdrawal of trophic support, i.e., nerve growth factor
      withdrawal, in vitro. Similarly, the monoamine oxidase inhibitor, deprenyl,
      promotes survival of facial motoneurons after axotomy. These pharmacological
      agents were assessed both alone and in combination for their ability to prevent
      death in non-nerve growth factor dependent CNS motoneurons after facial nerve
      axotomy in newborn rats. Long-term experiments were done with the
      diphenylpiperazines to evaluate potential enhancement of regeneration. Facial
      nerve transection resulted in 78% neuronal loss in the injured compared with the
      contralateral, uninjured nucleus. Systemic administration of diphenylpiperazines
      for 1 week after facial nerve transection doubled the number of surviving
      motoneurons from 23% to 47%. Similar results were obtained with deprenyl.
      Combinations of diphenylpiperazines and deprenyl provide a similar degree of
      neuronal protection 1 week after injury as that obtained by either agent alone.
      We assessed the ability of diphenylpiperazines to protect facial motoneurons from
      death over a prolonged period and enhance subsequent regeneration. Motor neuron
      counts in rats treated with diphenylpiperazines for 1 month after injury and
      assessed 2 months later demonstrated long-term enhancement of neuronal protection
      with an increase of 45% in the number of horseradish peroxidase-labelled
      motoneurons. The diphenylpiperazines group had approximately 80% more regenerated
      myelinated axons in the distal facial nerve than the control group. Thus,
      diphenylpiperazine treatment during the first month after injury provides long
      term protection of non-nerve growth factor dependent CNS motoneurons with
      subsequent potentiation of long-term facial nerve regeneration.

PMID- 9192298
TI  - Simultaneous measurement of intracellular Ca2+ and asynchronous transmitter
      release from the same crayfish bouton.
AB  - 1. A technique has been developed to monitor neurotransmitter release
      simultaneously with intracellular Ca2+ concentration ([Ca2+]i) in single release
      boutons whose diameters range from 3 to 5 microns. 2. Using this technique, we
      have found a highly non-linear relationship between the rate of asynchronous
      release and [Ca2+]i. The Hill coefficient lies between 3 and 4. 3. The affinity
      (Kd) of the putative release-related Ca2+ receptor for asynchronous release was
      calculated to be in the range of 2-4 microM. 4. The same range of values of Hill
      coefficient and Kd were obtained when [Ca2+]i was elevated both by bath
      application of ionomycin and by repetitive stimulation at high frequency. 5. Our
      results show that the Ca2+ receptor(s) associated with asynchronous release
      exhibits high affinity for Ca2+.

PMID- 9192299
TI  - Sodium channel distribution within the rabbit atrioventricular node as analysed
      by confocal microscopy.
AB  - 1. Paired 20 microns thick sections of fresh frozen tissue taken from the frontal
      plane of the rabbit atrioventricular (AV) nodal region were processed for
      histology and immunohistochemistry. Confocal microscopy was used to image the
      distribution of sodium channels using IgG (R12) developed against a highly
      conserved sequence in the interdomain 3-4 region of cloned sodium channels. 2. In
      ventricular and atrial cells, sodium channel immunofluorescence was localized to
      lateral membranes and T-tubules. In the open AV node, levels of sodium channel
      immunofluorescence in the transitional cell zone and in the lower nodal cell
      tract were comparable to that found in the atrial and ventricular myocardium. 3.
      In the enclosed AV node a gradation of sodium channel immunofluorescence is
      present such that peripherally located circumferential transitional cells display
      high levels of immunofluorescence, comparable to that of atrial and ventricular
      myocardium, while centrally located midnodal cells display decreased levels of or
      no immunofluorescence. 4. In order to correlate the distribution of sodium
      channels with the distribution of gap junctions, we used IgG directed against the
      carboxyl terminus of connexin43 (CT-360). Ventricular cell immunofluorescence was
      localized primarily to the intercalated disk region, while in the AV node, the
      pattern of distribution was found to be similar to that of sodium channels. 5.
      The reduced levels of and/or absence of immunofluorescence in the midnodal cell
      region indicates a paucity of sodium channel and connexin43 protein expression in
      this region of the AV node that would favour slow impulse conduction.

PMID- 9192300
TI  - The prostacyclin analogue carbacyclin inhibits Ca(2+)-activated K+ current in
      aortic baroreceptor neurones of rats.
AB  - 1. Previous studies indicate that prostacyclin (PGI2) increases the activity of
      baroreceptor afferent fibres. The purpose of this study was to test the
      hypothesis that PGI2 inhibits Ca(2+)-activated K+ current (IK(Ca))in isolated
      baroreceptor neurones in culture. 2. Rat aortic baroreceptor neurones in the
      nodose ganglia were labelled in vivo by applying a fluorescent dye (DiI) to the
      aortic arch 1-2 weeks before dissociation of the neurones. Outward K+ currents in
      baroreceptor neurones evoked by depolarizing voltage steps from a holding
      potential of -40 mV were recorded using the whole-cell patch-clamp technique. 3.
      Exposure of baroreceptor neurones to the stable PGI2 analogue carbacyclin
      significantly inhibited the steady-state K+ current in a dose-dependent and
      reversible manner. The inhibition of K+ current was not caused indirectly by
      changes in cytosolic Ca2+ concentration. The Ca(2+)-activated K+ channel blocker
      charybdotoxin (ChTX, 10(-7) M) also inhibited the K+ current. In the presence of
      ChTX or in the absence of Ca2+, carbacyclin failed to inhibit the residual K+
      current. Furthermore, in the presence of high concentrations of carbacyclin, ChTX
      did not cause further reduction of K+ current. 4. Carbacyclin-induced inhibition
      of IK(Ca) was mimicked by 8-bromo-cAMP and by activation of G-protein with GTP
      gamma S. The inhibitory effect of carbacyclin on IK(Ca) was abolished by GDP beta
      S, which blocks G-protein activation, and by a selective inhibitor of cAMP
      dependent protein kinase, PKI5-24. 5. The results demonstrate that carbacyclin
      inhibits ChTX-sensitive IK(Ca) in isolated aortic baroreceptor neurones by a G
      protein-coupled activation of cAMP-dependent protein kinase. This mechanism may
      contribute to the PGI2-induced increase in baroreceptor activity demonstrated
      previously.

PMID- 9192301
TI  - 'Quantal' calcium release operated by membrane voltage in frog skeletal muscle.
AB  - 1. Ca2+ transients and Ca2+ release flux were determined optically in cut
      skeletal muscle fibres under voltage clamp. 'Decay' of release during a
      depolarizing pulse was defined as the difference between the peak value of
      release and the much lower steady level reached after about 100 ms of
      depolarization. Using a double-pulse protocol, the inactivating effect of release
      was measured by 'suppression', the difference between the peak values of release
      in the test pulse, in the absence and presence of a conditioning pulse that
      closely preceded the test pulse. 2. The relationship between decay and
      suppression was found to follow two simple arithmetic rules. Whenever the
      conditioning depolarization was less than or equal to the test depolarization,
      decay in the conditioning release was approximately equal to suppression of the
      test release. Whenever the conditioning depolarization was greater than that of
      the test, suppression was complete, i.e. test release was reduced to a function
      that increased monotonically to a steady level. The steady level was the same
      with or without conditioning. 3. These arithmetic rules suggest that inactivation
      of Ca2+ release channels is strictly and fatally linked to their activation. More
      than a strict linkage, however, is required to explain the arithmetic properties.
      4. The arithmetic rules of inactivation result in three other properties that are
      inexplicable with classical models of channel gating: constant suppression,
      incremental inactivation and increment detection. These properties were first
      demonstrated for inositol trisphosphate (IP3)-sensitive channels and used to
      define IP3-induced release as quantal. In this sense, it can now be stated that
      skeletal muscle Ca2+ release is activated by membrane voltage in a quantal
      manner. 5. For both classes of intracellular Ca2+ channels, one explanation of
      the observations is the existence of subsets of channels with different
      sensitivities (to voltage or agonist dose). In an alternative explanation,
      channels are identical, but have a complex repertoire of voltage- or dose
      dependent responses.

PMID- 9192302
TI  - Functional and morphological features of skeletal muscle from mutant mice lacking
      both type 1 and type 3 ryanodine receptors.
AB  - 1. We generated mice with targeted disruptions in the genes for both ryanodine
      receptor type 1 (RyR-1) and type 3 (RyR-3) to study the functional roles of RyR
      subtypes in skeletal muscle. 2. In permeabilized myocytes lacking both the RyRs,
      the Ca(2+)-induced Ca2+ release (CICR) mechanism was completely lost, and
      caffeine failed to induce Ca2+ release. 3. Replacement of potassium
      methanesulphonate in an experimental intracellular solution with choline chloride
      resulted in Ca2+ release in the wild-type muscle but not in the mutant muscle
      lacking RyR-1. 4. The double-mutant mice exhibited more severe muscular
      degeneration than RyR-1-deficient mice with formation of large vacuoles and
      swollen mitochondria while structural coupling between T-tubules and the
      sarcoplasmic reticulum was retained. 5. These results demonstrate that CICR is
      mediated solely by RyR-1 and RyR-3 in skeletal muscle cells, and suggest that RyR
      1 is involved in Cl(-)-induced Ca2+ release. The results also suggest the
      presence of molecular components other than RyRs responsible for the triad
      formation. RyR-3 may have a role in the normal morphogenesis of skeletal muscle
      cells, although functionally it can be replaced by RyR-1.

PMID- 9192303
TI  - A novel role for HERG K+ channels: spike-frequency adaptation.
AB  - 1. The regular firing of a Hodgkin-Huxley neurone endowed with fast Na+ and
      delayed K+ channels can be converted into adapting firing by appending HERG
      (human eag-related gene) channels. 2. The computer model predictions were
      verified by studying the firing properties of F-11 DRG neurone x neuroblastoma
      hybrid cells induced to differentiate by long-term exposure to retinoic acid.
      These cells, which express HERG currents (IHERG), show clear spike-frequency
      adaptation of their firing when current clamped with long depolarizations. 3. In
      agreement with the prediction, the selective blocking of IHERG by class III
      antiarrhythmic drugs always led to the disappearance of the spike-frequency
      adaptation, and the conversion of adapting firing to regular firing. 4. It is
      proposed that, in addition to their role in the repolarization of the heart
      action potential, HERG channels may sustain a process of spike-frequency
      adaptation, and hence contribute to the control of burst duration in a way that
      is similar to that of the K+ currents, IAHP, IC and IM. In addition to the known
      cardiac arrhythmia syndrome (LQT2), genetic mutations or an altered HERG
      expression could lead to continuous hyperexcitable states sustained by the
      inability of nerve or endocrine cells to accommodate to repetitive stimuli. This
      might help in clarifying the pathogenesis of still undefined idiopathic familial
      epilepsies.

PMID- 9192304
TI  - K+ channels which contribute to the acetylcholine-induced hyperpolarization in
      smooth muscle of the guinea-pig submucosal arteriole.
AB  - 1. Membrane potentials were recorded from submucosal arterioles (diameter, 30-80
      microns) of the guinea-pig small intestine, using conventional microelectrode
      techniques. In control solution the resting membrane potential was about -73 mV,
      and the addition of 0.5 mM Ba2+ depolarized the membrane to about -43 mV. 2. ACh
      (10 nM to 10 microM), or substance P (0.1 microM), caused a membrane
      hyperpolarization in preparations which had been depolarized by Ba2+ but not in
      control preparations. ACh produced a sustained hyperpolarization, whereas
      substance P produced a transient hyperpolarization, without being affected by
      either nitroarginine (0.1 mM) or indomethacin (10 microM). 3. In the presence of
      50 microM BAPTA (acetoxymethyl ester form), the membrane potentials were not
      altered in the control solution or in the presence of Ba2+, but Ba2+ caused a
      smooth depolarization of the membrane. Following this procedure, both ACh and
      substance P caused membrane depolarization instead of hyperpolarization,
      suggesting that the ACh- and substance P-induced hyperpolarization in arteriolar
      smooth muscle are intracellular [Ca2+] dependent. 4. In short segments (200-500
      microns) of arteriole, the time constant of electrotonic potentials produced by
      passing current pulses through the recording electrode was about 75 ms. The
      addition of Ba2+ increased both the input resistance and the time constant. 5.
      The hyperpolarizations produced by ACh or substance P were associated with a
      reduction in the amplitude and the time constant of electrotonic potential. 6.
      The reversal potential for the ACh-induced hyperpolarization, estimated from the
      current-voltage relationship, was about -86 mV, a value close to the equilibrium
      potential for K+. 7. In the presence of 50 nM charybdotoxin the hyperpolarization
      produced by ACh became transient and was reduced in amplitude: the residual
      response was further reduced by apamin (0.1 microM). The response produced by
      substance P was also reduced by 50 nM charybdotoxin: again the residual response
      was sensitive to 0.1 microM apamin. The hyperpolarizations produced by either ACh
      or substance P were insensitive to glibenclamide (10 microM) and 4-aminopyridine
      (1 mM). 8. It is suggested that in submucosal arterioles of the guinea-pig ileum,
      ACh- or substance P-induced hyperpolarizations of smooth muscle result from
      activation of both charybdotoxin-sensitive and apamin-sensitive K+ channels, with
      the former being predominant. The results are discussed in relation to the
      possible involvement of one or more endothelium-dependent hyperpolarizing factors
      in ACh- and substance P-induced hyperpolarization.

PMID- 9192305
TI  - Evidence against the involvement of cytochrome P450 metabolites in endothelium
      dependent hyperpolarization of the rat main mesenteric artery.
AB  - 1. The influence of different inhibitors of cytochrome P450 mono-oxygenase on the
      endothelium-dependent and -independent hyperpolarization in the isolated rat main
      mesenteric artery was investigated. 2. Application of acetylcholine (ACh; 1
      microM) for 10 min evoked an endothelium-dependent peak hyperpolarization of
      about 18 mV followed by a partial recovery to a level 7 mV more negative than the
      resting value (-50.2 +/- 0.5 mV). 3. Proadifen (30 microM) completely and
      reversibly inhibited the ACh-induced hyperpolarization. Conversely, the imidazole
      antimycotics clotrimazole (30 microM) and miconazole (100 microM) had less effect
      on the peak endothelium-dependent hyperpolarization. The suicide substrate
      inhibitors 17-octadecynoic acid (17-ODYA; 5 microM) and 1-aminobenzotriazole (1
      ABT; 2 mM) did not significantly influence endothelium-dependent
      hyperpolarization. 4. The endothelium-independent hyperpolarization (16 mV)
      evoked by leveromakalim (300 nM) was completely inhibited by proadifen as well as
      by clotrimazole and miconazole but was not affected by 17-ODYA or 1-ABT. 5. These
      results do not support the view that the ACh-induced endothelium-dependent
      hyperpolarization in the rat mesenteric artery is mediated by cytochrome P450
      mono-oxygenase metabolites. Proadifen and imidazole antimycotics impair the
      activation of ATP-regulated K+ channels in mesenteric artery cells, rendering non
      specific inhibition of smooth muscle K+ channel activation an alternative
      explanation for the inhibitory influence of some (but not all) P450 inhibitors on
      endothelium-dependent hyperpolarization in this preparation.

PMID- 9192306
TI  - Stretch-activated whole-cell currents in smooth muscle cells from mesenteric
      resistance artery of guinea-pig.
AB  - 1. Stretch-activated (SA) channels were studied in smooth muscle cells isolated
      from mesenteric resistance arteries using the whole-cell patch-clamp method.
      Membrane stretch was achieved by cell inflation after application of positive
      pressure through a patch electrode. 2. In the voltage-clamp configuration, cell
      inflation increased and cell deflation decreased the membrane conductance.
      Conductance of the evoked current depended on the increase in cross-sectional
      area of the cell. The current-voltage relationship was linear between -80 and 0
      mV, while further hyperpolarization showed a slight inward rectification. 3. The
      reversal potential of the SA current depended on the extracellular Na+
      concentration, suggesting that the inward SA current was carried predominantly by
      Na+. The SA current was also carried by other cations, suggesting that the
      channel responsible for this current is a non-selective cation channel. The
      permeability sequence of cations as assessed by reversal potential was as
      follows: K+ > or = CS+ > or = Na+ > Li+. The channel was also permeable to Ca2+.
      4. Extracellular Ca2+ and Gd3+ inhibited the SA current carried by monovalent
      cations in a concentration-dependent manner with IC50 (concentration giving 50%
      of maximal inhibition) values of 0.9 mM and 14 microM, respectively. 5. In the
      current-clamp configuration, membrane stretch depolarized the cell, and 100
      microM Gd3+ inhibited the stretch-induced depolarization. 6. The results suggest
      that SA cation channels exist in arterial smooth muscle cells. Activation of the
      channels may modify membrane potential and intracellular ionic environment, and
      promote stretch-mediated cell responses.

PMID- 9192307
TI  - pH-dependent interactions of Cd2+ and a carboxylate blocker with the rat C1C-1
      chloride channel and its R304E mutant in the Sf-9 insect cell line.
AB  - 1. Gating of the skeletal muscle chloride channel (ClC-1) is sensitive to
      extracellular pH. In this study, whole-cell recording of currents from wild-type
      (WT) ClC-1 and a mutant, R304E, expressed in the Sf-9 insect cell line was used
      to investigate further the nature of the pH-sensitive residues. 2. Extracellular
      Cd2+ produced a concentration-dependent block of WT ClC-1 with an IC50 of 1.0 +/-
      0.1 mM and a Hill coefficient of 2.0 +/- 0.3. This block was sensitive to
      external pH, reducing at low pH, with an apparent pKa of 6.8 +/- 0.1 and a Hill
      coefficient for proton binding of 3.0 +/- 0.3. Anthracene-9-carboxylate (A-9-C)
      block of WT ClC-1 was also pH sensitive, increasing at low pH, with an apparent
      pKa of 6.4 +/- 0.1 and a Hill coefficient for proton binding of 1.0 +/- 0.2. 3.
      Compared with WT ClC-1, R304E had a lower affinity for Cd2+ (IC50, 3.0 +/- 0.3
      mM) but it had a similar Hill coefficient for transition metal ion binding. The
      Hill coefficient for proton binding to the Cd2+ binding site was reduced to 1.4
      +/- 0.3. In contrast, the A-9-C binding site in R304E showed the same pH
      sensitivity and affinity for the blocker as that seen in WT ClC-1. 4. ClC-1 has
      at least two binding sites for Cd2+, each of which has at least three residues
      which can be protonated. Binding of A-9-C is influenced by protonation of a
      single residue. Arg 304 is not sufficiently close to the A-9-C binding site to
      affect its characteristics, but it does. alter Cd2+ binding, indicating that
      transition metal ions and aromatic carboxylates interact with distinct sites. 5.
      The block of ClC-1 by transition metal ions and the apparent pKa of this block,
      together with the apparent pKa for A-9-C block and gating are all compatible with
      the involvement of His residues in the pore and gate of ClC-1.

PMID- 9192308
TI  - Amine precursor uptake and decarboxylation: significance for processing of the
      rat gastrin precursor.
AB  - 1. Conversion of prohormone precursors to smaller active products occurs in
      secretory granules, which also have the capacity to concentrate biogenic amines.
      We have examined how processing of the gastrin precursor, progastrin, in rat
      antral mucosa is influenced by modulation of the biogenic amine content of
      secretory granules. 2. Newly synthesized progastrin-derived peptides in rat
      antral mucosa were labelled in vitro with 35SO4(2-) using a pulse-chase protocol
      and detected after immunoprecipitation by HPLC with on-line liquid scintillation
      counting. Secretory granule morphology was examined by electron microscopy. The
      effects of experimentally manipulating secretory granule pH and amine content
      were examined. 3. The dopamine precursor L-beta-3,4-dihydroxyphenylalanine (L
      DOPA) inhibited cleavage of 35S-labelled thirty-four amino acid amidated gastrin,
      i.e. [35S]G34, and of [35S]G34 with COOH-terminal glycine, i.e. [35S]G34-Gly, at
      a pair of lysine residues, but did not influence cleavage of progastrin at pairs
      of arginine residues. The effect of L-DOPA was reversed by reserpine, which
      inhibits the amine-proton exchangers VMAT1 and VMAT2, and by carbidopa, which
      inhibits aromatic L-amino acid decarboxylase. 4. Treatments that raise
      intragranular pH, e.g. the weak base chloroquine, the ionophore monensin and the
      vacuolar proton pump inhibitor bafilomycin A1, had similar effects to L-DOPA. 5.
      Electron microscopical studies showed that the electron-dense aggregrates in
      gastrin cell secretory granules were lost after inhibition of the vacuolar proton
      pump. Treatment with L-DOPA produced reserpine-sensitive dissipation of the
      electron-dense aggregates, compatible with the idea that increased amine delivery
      raised intragranular pH. 6. The data suggest that the processes of amine
      precursor uptake, decarboxylation and sequestration in secretory granules are
      associated with selective modulation of progastrin cleavage, possibly by raising
      intragranular pH and thereby inhibiting pH-sensitive prohormone convertases.

PMID- 9192309
TI  - Contribution of selectins to leucocyte sequestration in pulmonary microvessels by
      intravital microscopy in rabbits.
AB  - 1. Sequestration of leucocytes in the lung is the net result of leucocyte rolling
      and sticking in pulmonary arterioles and venules and their retention in alveolar
      capillaries. 2. In order to investigate whether adhesion molecules of the
      selectin family contribute to these phenomena the effects of fucoidin (an
      inhibitor of L- and P-selectin) on microhaemodynamics and leucocyte kinetic were
      studied in pulmonary arterioles, capillaries and venules by means of intravital
      fluorescence microscopy in a rabbit model. 3. Fucoidin reduced leucocyte rolling
      in pulmonary arterioles and venules by 75 and 83%, respectively, without
      affecting leucocyte sticking. In alveolar capillaries, fucoidin reduced leucocyte
      retention and accelerated leucocyte passage, thus reducing the alveolar transit
      time of leucocytes by 62%. 4. It is concluded that rolling of leucocytes in
      pulmonary microvessels is mediated by selectins, whereas sticking relies on
      selectin-independent mechanisms. 5. Leucocyte retention in alveolar capillaries
      is not due solely to mechanical hindrance of leucocyte passage through narrow
      vessel segments, as previously hypothesized, but also depends on interaction of
      leucocytes with the capillary endothelium.

PMID- 9192311
TI  - Spatial and temporal frequency selectivity of cells in area 21a of the cat.
AB  - 1. The spatial and temporal response properties of single cells in area 21a of
      the anaesthetized cat were assessed using drifting sinusoidal gratings presented
      at the optimum orientation for each cell. 2. Responses to sinusoidal gratings
      were dominated by an elevation of the mean discharge, with a relatively small
      modulated component at the temporal frequency of grating drift. The relative
      modulation ratio for the majority of cells was less than 1, similar to complex
      cells in the striate cortex. 3. Of those cells responsive to stimulation with
      sinusoidal gratings, 94% displayed spatial bandpass characteristics. Values
      derived from spatial frequency tuning curves were: mean optimum spatial
      frequency, 0.26 cycles deg-1; mean spatial resolution, 0.86 cycles deg-1; mean
      spatial bandwidth, 1.8 octaves; and mean normalized bandwidth, 1.3. Two cells
      (6%) displayed spatial low-pass characteristics. 4. Approximately half our sample
      of cells (44%) displayed temporal low-pass tuning, while 35% displayed temporal
      bandpass characteristics. The mean optimum temporal frequency of bandpass cells
      was 3.3 Hz and the mean temporal bandwidth 1.9 octaves. The remaining cells were
      classified as temporal broadband (17%) and temporal high-pass (4%). 5. We
      conclude that the dominant functional input to cells with relatively high spatial
      frequency selectivity and/or temporal low-pass response properties most probably
      arises from area 17. The responses of the remaining cells may be explained by
      input from area 17 or 18.

PMID- 9192310
TI  - Presubicular and parasubicular cortical neurons of the rat: functional separation
      of deep and superficial neurons in vitro.
AB  - 1. The presubiculum and parasubiculum are retrohippocampal structures bordered by
      the subiculum and medial entorhinal cortex. Deep layer (IV-VI) neurons from this
      region exhibit stable synaptically triggered burst behaviour which distinguishes
      them from superficial layer (I-III) cells. This functional separation was
      examined with intracellular and field potential recordings from horizontal slices
      of rat brain. Neurobiotin labelling and rapid Golgi techniques were used to
      obtain anatomical evidence of axonal trajectories. 2. Extracellular stimulation
      of the subiculum, deep medial entorhinal cortex or superficial pre- or
      parasubiculum caused, in deep layer cells only, a short latency burst discharge
      which could be followed by one or more after-discharges. Bursts appeared after
      repetitive stimulation and were stable for the life of the slice. Each event was
      supported by giant excitatory postsynaptic potentials (EPSPs). Events were
      similar whether they were evoked in horizontal slices or slices cut perpendicular
      to the horizontal plane. 3. Bath application of the NMDA receptor antagonist 3-[2
      carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP; 5 microM) elevated the
      threshold for evoking the giant EPSP. Higher concentrations (10-15 microM)
      reduced the amplitude and duration of the giant EPSP. Bath application of the
      AMPA receptor antagonist beta-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5 microM)
      eliminated the evoked EPSP. 4. In intact slices, superficial layer neurons of pre
      and parasubiculum could exhibit EPSPs coincident with bursts recorded in the
      deep layers. However, in isolated subsections of horizontal slices or in
      'vertical slices', both of which contained only pre- and/or parasubiculum, evoked
      or picrotoxin-induced bursts occurred only in deep layer cells. Superficial layer
      cells in these subsections showed no response to deep layer events. 5. Antidromic
      population spikes confirmed projections from superficial cell layers of pre- and
      parasubiculum down to their deep cell layers. Reciprocal antidromic responses
      were absent. 6. Axons of superficial layer stellate and pyramidal cells had
      horizontal collaterals and at least one ascending and one descending collateral.
      Branches of the descending collaterals were given off in layer V and some axons
      were found to reach the angular bundle. Axons of deep layer stellate and
      pyramidal cells also had horizontal collaterals and descending collaterals which
      could be traced to the angular bundle. One ascending axon collateral was found
      among the thirty-one deep layer cells examined morphologically. 7. We conclude
      that the deep layer cells of the presubiculum and parasubiculum are richly
      interconnected with excitatory synapses. These interconnections can generate
      giant excitatory synaptic potentials that support the bursting behaviour
      exhibited by these neurons. Any of the excitatory inputs to deep layer cells can
      trigger the population bursts and specific inputs from entorhinal cortex produce
      the after-discharges. Further, connections between superficial and deep layer
      cells appear to be almost exclusively in the direction of superficial to deep.
      The absence of significant ascending input can account for the functional
      separation of superficial and deep layer neurons of presubiculum and
      parasubiculum.

PMID- 9192312
TI  - Non-NMDA receptors modulate respiratory drive in fetal sheep.
AB  - 1. Experiments were carried out in unanaesthetized fetal sheep to evaluate the
      significance of non-N-methyl-D-aspartate (non-NMDA) receptor neurotransmission in
      the expression of fetal breathing movements. Catheters placed in the trachea and
      amniotic fluid and electrodes beneath the parietal bones and in the nuchal muscle
      were used to monitor breath amplitude and frequency and fetal behavioural state.
      2. Experiments were carried out by instillation of neurotransmitter agonists,
      antagonists or receptor modulators into the cerebrospinal fluid (CSF) of the
      fourth ventricle by means of a chronic catheter introduced through the foramen
      magnum. 3. The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) decreased respiratory rate in a dose dependent manner by lengthening both
      inspiratory time (T1) and expiratory time (T0). 4. Kainate and (R,S)-alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) increased breath amplitude.
      Instillation of the antagonist 2,3-dihydro-6-nitro-7-sulphamoyl-benzo(f)
      quinoxaline (NBQX) prior to administering AMPA resulted in apnoea, which was not
      overcome by the agonist. 5. Cyclothiazide, which has been shown to prevent
      desensitization of AMPA receptors, caused an increase in both breath amplitude
      (152 +/- 73%; mean +/- S.D.; P = 0.004) and frequency (46 +/- 37%; P = 0.049). 6.
      These data suggest that glutamate acting at non-NMDA receptors is an essential
      component for the expression of fetal breathing movements, and that under resting
      conditions these non-NMDA receptors are desensitized following glutamate synaptic
      release.

PMID- 9192313
TI  - Chemosensory and cholinergic stimulation of fictive respiration in isolated CNS
      of neonatal opossum.
AB  - 1. The aim of the present experiments was to characterize the central chemical
      drive of fictive respiration in the isolated CNS of the newborn opossum,
      Monodelphis domestica. This opossum preparation, in contrast to those of neonatal
      rats and mice, produces respiratory rhythm of high frequency in vitro. 2. Fictive
      respiration was recorded from C3-C5 ventral roots of the isolated CNS of 4- to 14
      day-old opossums using suction electrodes. At room temperature (21-23 degrees C)
      the frequency of respiration was 43 +/- 5.3 min-1 (mean +/- S.E.M., n = 50) in
      basal medium Eagle's medium (BMEM) equilibrated with 5% CO2-95% O2, pH 7.37-7.40.
      Respiratory discharges remained regular throughout 8 h experiments and continued
      for more than 20 h in culture. 3. Superfusion of the brainstem confirmed that
      solutions of pH 6.3-7.2 increased both the amplitude and frequency of
      respiration. High pH solutions (7.5-7.7) had the opposite effect and abolished
      the rhythm at pH 7.7. Addition of ACh (50-100 microM) or carbachol (0.01-10
      microM) to the brainstem superfusion also increased the amplitude and frequency
      of respiratory activity, as did physostigmine (50-100 microM) or neostigmine (20
      50 microM). Conversely, scopolamine (50-100 microM) reduced the amplitude and
      frequency of the basal respiratory rhythm by about 30%. 4. H(+)- and cholinergic
      sensitive areas on the surface of the isolated CNS were explored with a small
      micropipette (outer tip diameter, 100 microns) filled with BMEM (pH 6.5) or 1
      microM carbachol. Carbachol applied to H(+)- and cholinergic-sensitive areas in
      the ventral medulla mimicked the changes of respiratory pattern produced by low
      pH application. Responses to altered pH and carbachol were abolished by
      scopolamine (50 microM). Histochemistry demonstrated several medullary groups of
      neurons stained for acetylcholinesterase. The superficial location of one of
      these groups coincided with a functional and anatomically well-defined pH- and
      carbachol-sensitive area placed medial to the hypoglossal roots. 5. Exploration
      of chemosensitive areas revealed that application of drugs or solutions of
      different pH to a single well-defined spot could have selective and distinctive
      effects upon amplitude and frequency of respiratory activity. 6. These results
      show that fictive respiration in the isolated CNS of the newborn opossum is
      tonically driven by chemical- and cholinergic-sensitive areas located on the
      ventral medulla, the activity of which regulates frequency and amplitude of
      respiration. They suggest that a cholinergic relay, although not essential for
      rhythm generation, is involved in the central pH chemosensory mechanism, or that
      cholinergic and chemical inputs converge upon the same input pathway to the
      respiratory pattern generator.

PMID- 9192315
TI  - Is energy expenditure in the hamster primarily under homeostatic or circadian
      control?
AB  - 1. In order to discriminate between homeostatic and circadian control of energy
      expenditure, this paper considers whether a shorter circadian cycle will produce
      a proportional reduction in energy expenditure (so that expenditure per unit time
      is conserved) or alternatively whether energy expenditure will be compressed into
      the shorter cycle (so that energy expenditure per cycle is conserved). To answer
      this question, we measured energy expenditure in tau mutant hamsters (whose free
      running circadian period has been reduced to about 20 h by a single gene
      mutation) and wild-type hamsters (whose free-running circadian period is about 24
      h). 2. In one experiment, the circadian rhythm of running-wheel activity of tau
      mutant hamsters was compared with that of wild-type hamsters. The rate of running
      was not affected by the mutation and, consequently, the total amount of activity
      per cycle was significantly less in mutants than in wild-type hamsters, whereas
      the total amount of activity per unit time was nearly the same. 3. In a second
      experiment, we measured energy expenditure by indirect calorimetry. Metabolic
      rate was not affected by the mutation and, consequently, the total amount of
      energy expended per cycle was significantly less in mutants than in wild-type
      hamsters but equivalent per unit time. 4. Because the amount of energy
      expenditure and locomotor activity was found to be proportional to the circadian
      cycle, we conclude that expenditure per unit time-rather than expenditure per
      circadian cycle-is conserved in the mutant animals. Therefore, we infer that
      energy expenditure in hamsters is primarily under homeostatic, not circadian,
      control. Further research is necessary to determine whether this inference can be
      applied to other species.

PMID- 9192314
TI  - The roles of adenosine in regulating the respiratory and cardiovascular systems
      in chronically hypoxic, adult rats.
AB  - 1. We have investigated the roles of adenosine in regulating the respiratory and
      cardiovascular systems of rats that were made chronically hypoxic for 3-4 weeks
      from 6 weeks of age (CH rats) in an hypoxic chamber at 12% O2. They were studied
      under anaesthesia while breathing 12% O2 and during acute hypoxia (breathing 8%
      O2 for 5 min) before and after addition of the adenosine receptor antagonist 8
      phenyltheophylline (8-PT, 10 mg kg-1). The results were compared with those
      obtained from normoxic (N) rats in a previous study. 2. CH rats breathing 12% O2
      had greater minute ventilation (VP) than N rats breathing air, but their levels
      of arterial blood pressure (ABP), heart rate (HR), femoral vascular conductance
      (FVC) and cerebral vascular conductance (CVC) were fully comparable. 8-PT
      increased tidal volume (VT) in CH rats indicating a greater tonic central
      inhibitory influence of adenosine on VT than in N rats. However, 8-PT had no
      effect on cardiovascular variables, indicating no tonic cardioinhibitory or
      vasodilator influence of adenosine in CH rats. 3. Acute hypoxia in CH rats
      increased VE such that at the 5th minute of 8% O2 absolute VE was comparable to
      that of N rats breathing 8% O2. Moreover, in CH rats 8-PT increased VT at the 5th
      minute of 8% O2 indicating that the central inhibitory influence of adenosine
      limits the ability to maintain VT in acute hypoxia as it does in N rats. 4. Eight
      per cent O2 also produced a full in ABP in CH rats that was comparable to that
      induced in N rats by the larger change from air to 8% O2. However, the changes in
      HR were similar in CH and N rats while the increases in FVC and CVC were smaller
      in CH rats. This suggests that the ability of the secondary effects of
      hyperventilation and of the baroreceptor reflex to maintain cardiac output and
      thereby ABP is reduced in CH rats. 5. Whereas 8-PT substantially reduced the
      hypoxia-induced increases in FVC and CVC in N rats, it had a small effect in CH
      rats (P = 0.054 and 0.06, respectively). Further, acute hypoxia in CH rats had no
      effect on the K+ concentration in the venous efflux of hindlimb K+ (KV+) before
      or after 8-PT treatment. We suggest that in CH rats, the dilator influence of
      adenosine in acute hypoxia occurs via actions on the blood vessel walls: there
      was no evidence that adenosine can release dilator concentrations of K+ from
      skeletal muscle fibres in CH rats as proposed for N rats.

PMID- 9192316
TI  - Maximum rate of oxygen uptake by human skeletal muscle in relation to maximal
      activities of enzymes in the Krebs cycle.
AB  - 1. Ten subjects performed incremental exercise up to their maximum work rate with
      the knee extensors of one leg. Measurements of leg blood flow and femoral
      arteriovenous differences of oxygen were made in order to be able to calculate
      oxygen uptake of the leg. 2. The volume of the quadriceps muscle was determined
      from twenty-one to twenty-five computer tomography section images taken from the
      patella to the anterior inferior iliac spine of each subject. 3. The maximal
      activities of three enzymes in the Krebs cycle, citrate synthase, oxoglutarate
      dehydrogenase and succinate dehydrogenase, were measured in biopsy samples taken
      from the vastus lateralis muscle. 4. The average rate of oxygen uptake over the
      quadriceps muscle at maximal work, 353 ml min-1 kg-1, corresponded to a Krebs
      cycle rate of 4.6 mumol min-1 g-1. This was similar to the maximal activity of
      oxoglutarate dehydrogenase (5.1 mumol min-1 g-1), whereas the activities of
      succinate dehydrogenase and citrate synthase averaged 7.2 and 48.0 mumol min-1 g
      1, respectively. 5. It is suggested that of these enzymes, only the maximum
      activity of oxoglutarate dehydrogenase can provide a quantitative measure of the
      capacity of oxidative metabolism, and it appears that the enzyme is fully
      activated during one-legged knee extension exercise at the maximal work rate.

PMID- 9192317
TI  - Paraesthesiae induced by prolonged high frequency stimulation of human cutaneous
      afferents.
AB  - 1. The present study has explored the behaviour of human cutaneous afferents
      following conduction of prolonged trains of impulses at 200 Hz for 10-20 min,
      correlating the resultant changes in excitability with the perception of
      paraesthesiae. 2. Tetanization for 10 min resulted in activity-dependent changes
      in axonal excitability, with an initial period of hyperexcitability, followed by
      a long-lasting subexcitability. All subjects experienced paraesthesiae soon after
      cessation of the tetanic train, and these subsided gradually over 16 min. 3.
      Longer tetanic trains of 20 min duration resulted in greater changes in axonal
      excitability, but with paraesthesiae of a similar time course. The post-tetanic
      increase in excitability was abolished when short tetanic trains were delivered >
      30 min before long trains, but all subjects still experienced paraesthesiae. 4.
      Threshold distributions following tetanic stimulation for both 10 and 20 min
      established that all axons contributing to the sensory volley underwent a uniform
      pattern of post-tetanic threshold changes. There was no evidence of a bimodal
      distribution with some axons hyperpolarized and others depolarized, as occurs
      with motor axons. However, the excitability changes were graded, with axons of
      lowest threshold undergoing a proportionately greater increase in excitability
      than axons of higher threshold. 5. The post-tetanic excitability changes were
      greater at the site of stimulation than elsewhere along the peripheral nerve.
      However, DC polarizing currents applied at this site failed to alter the
      sensation of paraesthesiae in the post-tetanic period. Furthermore, local
      anaesthetic block of the peripheral nerve proximal to the stimulation site failed
      to suppress the paraesthesiae. 6. The uniform pattern of post-tetanic threshold
      changes for cutaneous afferents differs from the bimodal distribution seen with
      post-ischaemic and post-tetanic motor axons. This difference in behaviour may
      reflect greater inward rectification and greater expression of a non-inactivating
      threshold conductance in cutaneous afferents. It is suggested that the ectopic
      activity responsible for paraesthesiae in the post-tetanic period arises from a
      more central site than the peripheral nerve.

PMID- 9192319
TI  - It's good to talk--and listen.

PMID- 9192318
TI  - Evidence suggesting a transcortical pathway from cutaneous foot afferents to
      tibialis anterior motoneurones in man.
AB  - 1. Stimulation of the superficial peroneal or the sural nerve (3 shocks, 3 ms
      interval, 1 ms duration, 2.5 x perception threshold) evoked a reflex activation
      of the tibialis anterior muscle at a latency of approximately 70-95 ms in all of
      nine healthy human subjects. Stimulation of the medial plantar nerve only rarely
      produced similar effects. The possibility that a transcortical pathway
      contributes to these late reflex responses was investigated by combining the
      cutaneous stimulations and a transcranial magnetic stimulation of the
      contralateral motor cortex. 2. A significant facilitation of short-latency peaks
      in the post-stimulus time histogram of single tibialis anterior motor units
      evoked by the transcortical magnetic stimulation was observed in eight out of
      nine subjects following stimulation of the superficial peroneal or sural nerves
      at the latency of the long-latency reflex. In contrast such a facilitation was
      only rarely seen when the medial plantar nerve was stimulated. 3. With the same
      timing for the stimuli, the superficial peroneal and sural nerve stimulations
      also produced a significant increase in the short-latency, presumed monosynaptic,
      facilitation of the tibialis anterior H reflex produced by the brain stimulation.
      4. Similar facilitatory effects of the cutaneous stimuli could not be
      demonstrated when the magnetic stimulation of the cortex was replaced with
      electrical stimulation, implying that cortical excitability is affected by a
      conditioning cutaneous stimulation. 5. It is suggested that the long-latency
      reflexes in the tibialis anterior muscle evoked by activation of cutaneous
      afferents from the human foot are, at least partly, mediated by a transcortical
      pathway.

PMID- 9192320
TI  - Psoriasis.

PMID- 9192321
TI  - Recent advances in atopic dermatitis.

PMID- 9192322
TI  - Skin cancer.

PMID- 9192323
TI  - Ultraviolet phototherapy.

PMID- 9192324
TI  - Medication for older people. Summary and recommendations of a report of a working
      party of The Royal College of Physicians.

PMID- 9192325
TI  - Improving communication between doctors and patients. Summary and recommendations
      of a report of a working party of The Royal College of Physicians.

PMID- 9192326
TI  - Increasing demand for dermatological services: how much is needed?

PMID- 9192327
TI  - Paradise regained: insights into coronary heart disease prevention from recent
      clinical trials and basic research.
AB  - Many of the uncertainties regarding the place of lipid lowering in the prevention
      of coronary heart disease have recently been resolved. Some of the newer findings
      are reviewed, and the scope for a revised clinical approach examined. The results
      of trials of lipid lowering, based on clinical end-points and particularly on
      angiographic end-points, and their meta-analyses are discussed. The close
      relation between coronary-angiographic and clinical outcomes is reviewed in
      relation to recent advances in understanding of the underlying arterial
      pathology, and possible underlying mechanisms are proposed. The variables
      predictive of progression of coronary artery disease, including nutrient intake,
      are examined. The management of hyperlipidaemia requires that treatment and
      therapeutic goals are consonant with the patient's cardiovascular risk; for this
      purpose, clinical and biochemical assessment of risk may be enhanced by
      angiographic and non-invasive methods to detect potentially-infarctogenic
      atherosclerotic lesions.

PMID- 9192328
TI  - Managing heart failure in a specialist clinic.
AB  - Patients with heart failure are often inadequately investigated and treated in
      general practice. To improve the management of heart failure locally we initiated
      a specialist clinic in 1994. After its first 18 months, we audited the outcome of
      general practitioners' referrals to the clinic to examine its effectiveness in
      improving the diagnosis and treatment of heart failure. Eighty-five patients were
      referred with suspected heart failure. However, only 48% had echocardiographic
      evidence of left ventricular systolic dysfunction. Following referral, 80% of
      these patients were given a trial of angiotensin-converting enzyme inhibitors
      compared with 27% before referral. Six patients were receiving angiotensin
      converting enzyme inhibitors unnecessarily, and five patients had significant
      structural cardiac disorders. Referral to a specialist clinic improved the
      accuracy of diagnosis and the number of patients on appropriate treatment.
      Greater use of open access echocardiography prior to referral might have allowed
      a more selective (and cost-effective) utilisation of the clinic.

PMID- 9192329
TI  - Management and health status in the first year after out-of-hospital cardiac
      arrest.
AB  - The one-year survival, functional and cerebral capacity and patient management
      following out-of-hospital cardiac arrest were examined in a follow-up study of
      143 prospectively identified patients discharged from a West Yorkshire hospital
      between January 1987 and July 1993. One-year survival was 87%; 13 of the 18
      deaths were cardiac related; 89% of survivors had no further cardiac related
      admissions; 98% of patients surviving to one year were capable of independent
      daily activities. There was low utilisation of simple drug therapy: 23% of
      patients were discharged taking beta-blockers and 52% aspirin; 50% of patients
      discharged after a primary arrhythmic event were taking antiarrhythmic therapy or
      were given an implantable defibrillator. Irrespective of the availability of
      invasive cardiac facilities, there was underutilisation of investigations: only
      39% of patients were seen by a cardiologist and 54% were not evaluated for
      ischaemic risk. Significant improvements in patient management could probably be
      achieved quickly without substantial increases in resources.

PMID- 9192330
TI  - Continuing health care criteria: their use in a specialist disability service.
AB  - OBJECTIVE: to evaluate the British National Health Service (NHS) criteria for
      determining eligibility for continuing health care when applied to a population
      of younger people with severe, usually neurological disability. DESIGN: an
      observational study with descriptive analysis of the data. SETTING: the
      specialist disability service catering to the population of Oxfordshire
      (560,000). SUBJECTS: 196 patients in contact with the specialist services in
      January 1996. INTERVENTION: senior staff graded the extent to which each patient
      had one or more of five health and three non-health needs addressed by the
      service (rated on a scale of 0-3 for each item). MEASURES: the Oxfordshire Health
      Authority guidelines for determining eligibility were used, with an additional
      three criteria covering non-health needs (social interaction, supporting carers,
      supporting Social Service care packages). RESULTS: 196 patients were assessed:
      128 (65%) had all health and non-health needs being satisfied by the service;
      multiple needs were being met in 165 (84%). Only 18 (9%) had no health needs
      being met. There was no clear-cut separation either between different categories
      of health need or between health and non-health needs. CONCLUSION: the current
      categories cannot be applied at the level of individual patients without conflict
      because: they are unclear, not being based on any logical, coherent framework in
      almost all patients the needs being met by health services include many non
      health needs.

PMID- 9192331
TI  - Folate assays: serum or red cell?
AB  - Tests for folate and vitamin B12 deficiency are frequently requested by
      clinicians in many different specialties. An audit of folate assay methodology
      was undertaken to establish the number of tests and types of assay performed in
      different centres, and to analyse the indications for these investigations, with
      a view to advising on the most appropriate assay for use in the laboratory. A
      questionnaire was sent to 30 centres, 24 (80%) of which participated in the
      audit. The types of folate assay performed, number of requests, reference range
      and method of analysis differed between centres. The major specialty users of the
      service were general practitioners, general physicians and geriatricians. A
      detailed analysis of 1,259 consecutive requests for folate assays from a single
      representative laboratory showed a significant correlation between serum and red
      cell folate levels (r = 0.49, p < 0.001). However, in patients with low serum
      folate, there was no correlation with red cell folate in the absence of
      macrocytosis. The major indication for folate analysis was for haematological
      abnormalities but 36% of cases were for nonspecific indications. A haematologist
      with an interest in folate metabolism was invited to moderate the results at an
      audit meeting of haematologists. The consensus was that the most appropriate
      screening test for folate deficiency is the serum assay, which can be combined
      easily with vitamin B12 assay.

PMID- 9192332
TI  - Detecting homicide in hospital.
AB  - The Beverly Allitt case and the subsequent inquiry have focused attention on the
      detection of covert hospital homicide. Effective investigation can only take
      place if there is prompt recognition of circumstances that justify suspicion
      about a death and immediate action is taken to retrieve potentially vital
      evidence. The hospital itself must take responsibility for the detection of
      covert homicide. Confidence that such deaths will be uncovered by 'routine'
      investigation through the existing coroner system, including postmortem
      examination, is misplaced.

PMID- 9192333
TI  - Notification of tuberculosis: an updated code of practice for England and Wales.

PMID- 9192334
TI  - Health profiles of current and former smokers and lifelong abstainers. OXCHECK
      Study Group. OXford and Collaborators HEalth ChecK.
AB  - The aim of this study was to determine the extent to which smokers and smoking
      quitters differ in habits and risk factors from non-smokers. Subjects comprised
      8,109 patients aged 35-67 years having health checks in British primary care. We
      compared lifestyle and measured cardiovascular risk factors in smokers, former
      smokers and lifelong abstainers in cross-sectional analyses, and in prospective
      data in quitters. Results were adjusted for confounding factors. Considering 25
      aspects of lifestyle, smokers had significantly worse habits in 20 compared to
      abstainers, and in 17 compared to former smokers. These included eating more
      white bread, full cream milk, fried food and meat, and less fruit and vegetables,
      wholemeal bread and bran cereals. Smokers report drinking more alcohol and taking
      less exercise. Smokers' mean serum levels were higher for total and low density
      lipoprotein cholesterol and triglycerides and lower for high density lipoprotein
      cholesterol. Within five years ex-smokers' data became comparable to lifelong
      abstainers for most factors, with apparent attenuation over up to 20 years for
      triglyceride, body mass index and scores for fibre and polyunsaturated fat
      intake. Smokers who quit after initial examinations had better health profiles
      even before quitting (p = 0.016) and subsequently made more beneficial health
      changes (p = 0.039) than continuing smokers. Smoking is associated with
      relatively poor health choices and risk factor levels. Stopping smoking is
      associated with a wide range of improved health markers beyond avoidance of
      tobacco toxicity.

PMID- 9192335
TI  - Computers can be compatible with confidentiality.

PMID- 9192337
TI  - The development and testing of a cardiac rehabilitation audit tool.
AB  - Cardiac rehabilitation is a multidisciplinary activity and as such necessitates
      the development of audit systems that cut across professional boundaries. The
      objective of this paper is to describe the development and testing of an audit
      tool for cardiac rehabilitation. The tool, based on published guidelines,
      comprised three proformas: one for each patient entering a cardiac rehabilitation
      programme, one for a summary of a series of patients and one for the facilities
      available. The proformas were tested in three centres that were assessed as
      either 'high', 'moderate' or 'low' providers of cardiac rehabilitation. The
      cardiac rehabilitation programme coordinator of each centre examined a
      consecutive series of 30 patients' case notes and completed the proformas. The
      proformas were found to be clear and easy to use. Information was obtained that
      informed users of current practice and provided pointers to improvements in the
      provision of care. In conclusion, the cardiac rehabilitation audit tool proved to
      be effective in determining the documented evidence of practice, was better for
      determining the level of provision than a purely subjective judgement and
      provided information indicating an individual programme's strengths and
      weaknesses. This is the first attempt at producing an audit tool for cardiac
      rehabilitation. However, further work may be required in its refinement.

PMID- 9192336
TI  - Cardioversion of atrial arrhythmias: audit of anticoagulation management.
AB  - Patients undergoing cardioversion for chronic atrial fibrillation should receive
      anticoagulation for three weeks before and four weeks after the procedure.
      Patients with atrial flutter and acute atrial fibrillation are also at risk of
      thromboembolic complications, so they too should be anticoagulated for
      cardioversion. Of the 36 acutely admitted patients who were cardioverted, 18 were
      in atrial fibrillation and 18 in atrial flutter. All except three of those in
      fibrillation were anticoagulated with heparin before cardioversion, but only
      seven received warfarin after cardioversion. Of those in flutter, 10 received
      heparin and eight received no anticoagulation before cardioversion. One patient
      underwent transoesophageal echocardiography before cardioversion to exclude
      atrial thrombi. Only two patients received warfarin for a month after
      cardioversion. Of the 20 elective cardioversions, 10 were in atrial fibrillation
      and 10 in atrial flutter. Five of those in fibrillation had received at least
      three weeks' treatment with warfarin before cardioversion and two underwent
      transoesophageal echocardiography; the other three received either up to two
      hours of heparin or no anticoagulation before cardioversion. Only five patients
      received warfarin for a month after cardioversion. Nine of those in flutter
      received a few hours of heparin before cardioversion and one was not
      anticoagulated; none underwent transoesophageal echocardiography or received
      warfarin after cardioversion. The results of this audit demonstrate that
      anticoagulation for atrial arrhythmias was inconsistent and often inadequate. A
      formal anticoagulation policy for cardioversion has now been adopted.

PMID- 9192338
TI  - Exploring vascular nitric oxide in health and disease. The Goulstonian Lecture
      1996.

PMID- 9192339
TI  - Molecular medicine: from laboratory to clinical practice.

PMID- 9192340
TI  - The college suspended.
AB  - A satirical account of the raising of the Royal College of Physicians and its
      suspension from a balloon for three months is included among Baron Munchausen's
      later surprising adventures. Portrayals by artists of this flight of fancy
      involving the College are not widely known. Three pictorial representations of
      the raising of the College are shown and some of the historical context of the
      tall tale is given.

PMID- 9192341
TI  - Failure of patients to attend a medical outpatient clinic.

PMID- 9192342
TI  - Failure of patients to attend a medical outpatient clinic.

PMID- 9192343
TI  - Power without responsibility.

PMID- 9192344
TI  - Urinary tract infection in women.

PMID- 9192345
TI  - Cardiac catheterisation in patients with infective endocarditis.

PMID- 9192346
TI  - Calman's not for me.

PMID- 9192347
TI  - The acute uraemic emergency.

PMID- 9192348
TI  - 'Brain attack'.

PMID- 9192349
TI  - Dame Mary Page.

PMID- 9192350
TI  - Recombinant viral vector vaccines for the veterinary use.
AB  - Recently, genetically engineering using recombinant DNA techniques has been
      applied to design new viral vaccines in order to reduce some problems which
      present viral vaccines have. Up to now, many viruses have been investigated for
      development of recombinant attenuated vaccines or live viral vectors for delivery
      of foreign immunogenic antigens. In this review, we introduced three kind of
      viruses; herpesviruses, vaccinia viruses, and adenoviruses, which have best
      widely been studied as recombinant vaccines or delivery vaccines for the
      veterinary use.

PMID- 9192351
TI  - Effects of quaternary ammonium compounds with 0.1% sodium hydroxide on swine
      vesicular disease virus.
AB  - The effects of quaternary ammonium compounds (QACs) with sodium hydroxide on
      swine vesicular disease virus (SVDV), an enterovirus were studied.
      Didecyldimethylammonium chloride (DDAC) with 0.1% NaOH showed a stronger effect
      against SVDV than other QACs with 0.1% NaOH. The effect of DDAC with 0.1% NaOH
      was strong at 40 degrees C. DDAC was effective against SVDV at pH values around
      11.0, but not in the distilled water control. The effect of DDAC with 0.1% NaOH
      was already observed at 1 min after mixing of the DDAC with SVDV. Observation
      under an electron microscopy revealed that the probable mechanism of inactivation
      of DDAC with 0.1% NaOH is as follows: The virus particles were partially
      destroyed by 0.1% NaOH. DDAC gathered these affected particles and formed a
      micelle, then SVDV lost its infectivity. From these results, QACs with 0.1% NaOH
      are considered to be very effective against SVDV representing enteroviruses.

PMID- 9192352
TI  - Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in
      adult rats with special reference to inhibin secretion.
AB  - Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male
      rats were examined. To clarify the role of adrenal glucocorticoids in gonadal
      function, the effects of adrenalectomy and Dexamethasone treatment were also
      investigated. Ether stress increased the plasma concentrations of ACTH and
      corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and
      testosterone. The pituitary responsiveness to LH-RH for LH release and testicular
      responsiveness to the endogenous LH for testosterone release were maintained in
      stressed rats. Adrenalectomy caused an increase in the plasma concentrations of
      ACTH, but decreased the plasma concentrations of LH, FSH and testosterone.
      Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma
      gonadotropins to control levels. The concentration of plasma inhibin did not
      change in adrenalectomized rats, but it was decreased compared to control rats by
      Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted
      in a decline in plasma levels of testosterone and inhibin without a decrease in
      the levels of LH and FSH, indicating the direct effect of Dexamethasone on the
      testes. These results indicate that increased ACTH secretion in stressed rats is
      probably due to hypersecretion of CRH from the hypothalamus, which suppresses
      gonadotropin secretion via the inhibition of LH-RH. The decreased levels of
      testosterone may be caused by a stress-induced decrease in plasma LH
      concentrations and increased secretion of corticosterone in the ether stressed
      rats. The low levels of plasma inhibin in stressed rats was also probably due to
      the direct effect of corticosterone on the Sertoli cells.

PMID- 9192353
TI  - Application of maximal removal rate of indocyanine green to the determination of
      hepatic functional mass in conscious rats.
AB  - We established a versatile method for the measurement of indocyanine green
      maximal removal rate (ICG Rmax) to detect hepatic functional mass in conscious
      rats using a repeated blood sampling procedure. On investigation of the optimal
      technical conditions, the appropriate intravenous administered doses of ICG were
      2.5, 5, 10 or 20 mg/kg, and the best blood collection times for calculating
      plasma half-life at these doses were immediately before, and 4, 7 and 10 min
      after ICG injection. The interval among the respective ICG injections was more
      than 4 hr. In hepatectomized rats, the ICG Rmax value was reduced to about 50%
      and 20% of sham-operated rats in mean 2/3 and 4/5 liver resections, respectively,
      suggesting that it would almost extrapolate to hepatic surviving reserves under
      these experimental conditions. In rats treated subcutaneously with carbon
      tetrachloride (CCl4, 0.1 and 0.25 ml/kg) thrice weekly during a 17-week period
      (120 days), a decrease in ICG Rmax value did not correlate with increases in
      serum alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin
      values throughout the experimental periods. However, the reduced ICG Rmax well
      correlated with decreases in serum albumin and cholinesterase (CHE) values from
      day 50. Histological examinations in the liver revealed that nodules of
      hepatocytes were separated by thick fibrous bands, defining the typical aspect of
      cirrhosis on day 30 to 90. These results suggest that the measurement of ICG Rmax
      is a valuable tool for the estimation of hepatic functional integrity in rats.

PMID- 9192354
TI  - A possible role of a blood vessel in formation of the fat area in the quadrate
      lobe of porcine liver.
AB  - Approximately a half of swine examined had a fat storing area (F-area) in the
      quadrate lobe of the liver. This area was stained strongly by Sudan Black B (fat
      staining) and PAS (carbohydrate staining). The area was light brown to greyish
      yellow in appearance due to the deposition of lipid droplets. In cross section
      the F-area was wedge-shaped, and had a specific venous supply which directly
      connected it to the right gastric vein. The larger the connecting vein the wider
      the F-area, indicating that the connecting vein, not reported so far, is a key
      factor in the formation of the F-area. This would be a good model for the
      formation of partial fatty liver.

PMID- 9192355
TI  - Comparison of systemic and renal hemodynamics measured by Doppler ultrasonography
      in canine experimental hypovolemia.
AB  - The aim of this study was to examine renal hemodynamics at the hypovolemic and
      recovery phases in two different hypovolemic shock models using Doppler
      ultrasonography, and to compare this with systemic hemodynamics. In experiment 1,
      the hypovolemic phase was induced in 6 mongrel dogs by removing arterial blood at
      30 ml/kg for 60 min. In the recovery phase, this blood was reinfused at 30 ml/kg
      over 60 min. In experiment 2, hypovolemia was induced in 12 beagle dogs by rapid
      blood removal until blood pressure decreased to 40 mmHg and was maintained at
      this pressure for 30 min. Six of the dogs were then infused with 20 ml/kg
      hydroxyethyl starch over 5 min, and the other 6 were infused with 60 ml/kg
      lactated Ringer's solution also over 5 min. Parameters for systemic and renal
      hemodynamics were measured by using a polygraph and the Doppler method,
      respectively. The decrease of diastolic blood flow, resulted in an increase of
      vessel resistance, and was detected in the hypovolemic kidney by the Doppler
      method. The rapid and large volume infusion of resuscitation fluids was effective
      for the recovery of both systemic circulation and renal blood flow, however this
      induced an increase of kidney vessel resistance, a result of the autoregulation
      mechanism of the kidney. The changes in these parameters at the main renal artery
      and interlobar artery were similar.

PMID- 9192356
TI  - Apoptosis-like cell death in experimentally-induced cryptorchidism in adult mice.
AB  - In order to elucidate the mechanism of germ cell degeneration in experimental
      cryptorchidism, we examined the testes of adult mice from a morphological
      standpoint. Adult ICR mice were made cryptorchid either unilaterally or
      bilaterally. In some mice, testes were surgically replaced back into the scrotum
      at 2 months after induction of cryptorchidism to observe the regenerative
      process. Morphological changes of cryptorchid and replaced testes have been
      studied by light and electron microscopy. Testes were also examined by the TUNEL
      (TdT-mediated dUTP-biotin nick end labelling) method to evaluate whether the
      degenerative cells, spermatocytes and spermatids, were dying by apoptosis or by
      any other process(es). At 8 weeks after the induction of cryptorchidism, the
      seminiferous epithelium consisted only of Sertoli cells, spermatogonia, and some
      spermatocytes of early meiotic stages. Soon after the replacement of testes to
      the scrotum, most of the seminiferous tubules resumed spermatogenic processes.
      Many degenerating cells, especially the spermatocytes, showed condensation of the
      nucleus and cytoplasm in cryptorchid testes. Although the cytoplasm was markedly
      eosinophilic under a light microscope to imply condensation of the cytoplasm, the
      extent of the condensation was not as pronounced under an electron microscope as
      reported in previous publications. The cytoplasm showed no expansion. By the
      TUNEL method, many of the degenerating cells, mainly the spermatocytes, have been
      shown as undergoing apoptosis. These data provide evidence that at least some of
      the cells die by apoptosis, or by a process similar to apoptosis.

PMID- 9192357
TI  - Variation from cytopathogenic biotype to non-cytopathogenic biotype is correlated
      with the deletion of cellular sequence from bovine viral diarrhea viruses.
AB  - Non-cytopathogenic (NCP) viruses of bovine viral diarrhea (BVD) virus were
      detected at a low ratio by the reverse plaque formation method from virus samples
      after several plaque clonings of cytopathogenic (CP) BVD viruses; NADL and Osloss
      strains. This phenomenon suggests that the NCP BVD viruses are produced at a low
      ratio during the propagation of CP BVD viruses in vitro. To investigate the
      differences between the parent CP BVD virus and the NCP BVD virus as a real
      progeny, the regions flanking the insertion of cellular mRNA in the p125 domain
      of NADL and Osloss strains were amplified by RT-PCR and cloned into pGEM 3Z
      plasmid vector, and then sequenced. Consequently, it was confirmed that sequences
      of cellular mRNA insertion of CP BVD viruses, NADL and Osloss strains, were
      completely and exactly deleted from the NCP BVD viruses which were real progeny
      of CP BVD viruses, NADL and Osloss strains. These results suggest that NCP BVD
      viruses may revert from CP biotype to NCP biotype by the deletion of cellular
      mRNA insertion in the viral genome of CP BVD viruses (NADL and Osloss strains).

PMID- 9192358
TI  - Ultrasound-guided follicle aspiration and IVF in dairy cows treated with FSH
      after removal of the dominant follicle at different stages of the estrous cycle
      [corrected].
AB  - Recently, transvaginal ultrasound-guided follicle aspiration technology has been
      found to be of great value for in vitro fertilization (IVF) programs, even though
      the oocyte recovery rate and cleavage rate of transferrable embryos were low. In
      this study, we investigated the effect of the removal of the dominant follicle at
      different stages of the estrous cycle on the ovarian response of donor cows. Four
      experiments (EXPs) were devised. In EXP 1, 3 cows received 20 mg FSH on Day 1,
      ovulation occurred on Day 0, and on Day 3 follicles were aspirated. In EXP 2, the
      dominant follicle of the first wave was removed on Day 6 from 3 cows which
      received 20 mg FSH on Day 7 and on Day 9 follicles were aspirated. In EXP 3, 2
      pregnant cows received 20 mg FSH on 70 d of pregnancy and 48 hr later follicles
      were aspirated a total of 5 times at 5-day intervals. In EXP 4, after ovulation
      on Day 0, 9 cows received 20 mg FSH on Days 8 to 14 of the estrous cycle and 48
      hr after the last injection, follicles were aspirated once. The respective mean
      +/- SD numbers of aspirated follicles and recovered oocytes were higher (p <
      0.01) in EXP 1 (13.4 +/- 1.7 and 8.7 +/- 2.3), EXP 2 (12.1 +/- 1.4 and 7.7 +/-
      1.7) and EXP 3 (10.7 +/- 2.1 and 7.0 +/- 2.2) than in EXP 4 (5.8 +/- 2.3 and 3.1
      +/- 1.6). The oocyte recovery rates were higher (p < 0.05) in EXP 1, EXP 2 and
      EXP 3 than in EXP 4. Similarly, the respective numbers of viable oocytes and
      cleavage rates were higher in EXP 1, EXP 2 and EXP 3 (6.0 +/- 1.3, 5.0 +/- 1.1
      and 4.6 +/- 1.5 viable oocytes (p < 0.01); 66, 73 and 65% cleavage rates (p <
      0.05)) than in EXP 4 (2.4 +/- 1.1; 46%). The numbers of morulae and blastocysts
      were higher (p < 0.05) in EXP 1, EXP 2 and EXP 3 than in EXP 4. In conclusion 1)
      removal of the dominant follicles from lactating and pregnant cows enabled viable
      oocytes to be recovered constantly and repeatedly by aspiration at different
      reproductive stages, and that viable blastocysts can be produced after IVF. 2)
      The presence or absence of a dominant follicle significantly affects the ovarian
      responses to FSH treatment. 3) This ultrasound-guided procedure proved to be an
      effective, repeatable and safe method for viable oocyte recovery from valuable
      pregnant donors.

PMID- 9192359
TI  - Virus neutralizing antibody titer to feline immunodeficiency virus isolates of
      subtypes A, B and D in experimentally or naturally infected cats.
AB  - Six strains of feline immunodeficiency virus (FIV) classified into subtypes A, B
      and D were examined by cross-neutralization test using Kumi-1 cells (CD4+, CD8+,
      and CD9+), an interleukin-2 dependent feline T-lymphocyte cell line. Neutralizing
      activities against these six FIV strains were also investigated in 50 FIV
      antibody-positive serum samples collected from different geographical regions in
      Japan. The cross-neutralization test revealed that antisera against the six
      strains tended to possess high neutralizing activity against the homologous
      strain. These antisera were also capable of neutralizing viral strains of the
      same subtype. However, some of the antisera were broadly crossreactive with all
      six FIV strains. Serum samples collected from naturally infected cats in the
      field showed various neutralization patterns for the six FIV strains. These
      observations reflect the antigenic diversity in FIV strains prevailing in the
      field. There were also broadly crossreactive serum samples, and 36% (18/50
      samples) showed neutralization for all six FIV strains.

PMID- 9192360
TI  - Malignant aortic body tumor in a Holstein cow.
AB  - A malignant aortic body tumor was observed in a 5-year-old female Holstein cow.
      The neoplastic mass, of 22 x 17 x 15 cm in size, was located at the base of the
      left atrium, having irregular lobular structures. The tumor cells had slightly
      eosinophilic cytoplasm, and a round or oval nucleus. Metastasis was only present
      in the premediastinal lymph node. The tumor cells exhibited intense
      immunoreactivity for neuron-specific enolase (NSE) and synaptophysin, and were
      moderately positive for chromogranin A. Electronmicroscopy revealed membrane
      limited granules in the cytoplasm. The cultured cells were spindle in shape, and
      having projectional cytoplasm. They were intensely positive for NSE,
      synaptophysin, chromogranin A, and neurofilament (200 kD). Consequently, this
      case was diagnosed as a malignant aortic body tumor from the neuroecrodermal
      origin.

PMID- 9192361
TI  - Olecranon lesions caused by Onchocerca skrjabini in wild Japanese serows
      (Capricornis crispus).
AB  - Wild Japanese serows (Capricornis crispus) were found to have parasitic lesions
      in tendons that attached the musculus tricepus brachii to the olecranon.
      Histopathological study of the lesions showed chronic tendinitis with multiple
      granulation nodules around the worms. The lesions were found in 138 of the 353
      serows examined and were more frequent in aged animals than young ones.
      Transverse ridges on the cuticle of the female midbody, the sizes and
      morphological features of the spicules, and the arrangement of the caudal
      papillae of the males showed the parasite to be Onchocerca skrjabini. Therefore,
      O. skrjabini causes olecranon lesions in addition to fibrous bursa formation in
      carpal and tarsal regions of the Japanese serows.

PMID- 9192362
TI  - Immunomapping of basement membrane zone macromolecules in canine salt-split skin.
AB  - Certain macromolecules of human and canine cutaneous basement membrane zone (BMZ)
      have shown to have responsibilities for pathogenesis of mechanobullous skin
      diseases. Salt-split skin by 1 M NaCl have been used for diagnosis of human
      mechanobullous diseases. However, there have been no studies to characterize
      canine salt-split skin. Electron microscopy of canine salt-split skin showed the
      separation within lamina lucida. Indirect immunofluorescence revealed the roof of
      the cleft was labeled by human patient serum with bullous pemphigoid, whereas
      laminin, laminin 5, type IV and type VII collagen were labeled at the bottom of
      the cleft. It is suggested that immunomapping of salt-split skin may be useful
      for the differential diagnosis of canine mechanobullous diseases.

PMID- 9192364
TI  - Characterization and treatment of 20 canine dominance aggression cases.
AB  - This study was undertaken to characterize 20 cases of dominance aggression seen
      at Tufts University School of Veterinary Medicine and to investigate the efficacy
      of our non-confrontational behavior modification program for 8 weeks. The 20
      cases included 18 pure breed and 2 mixed breed dogs. Thirteen of the dogs were
      male. The dogs' ages ranged from 7 to 84 months (mean 32.1 +/- 22.64 SE). There
      was no correlation between the severity of dominance aggression and the
      signalment of the dogs. At the conclusion of the eight week follow up period, 14
      dogs (70%) were reported to have responded to the treatment to some degree. Six
      dogs did not demonstrate any noticeable reduction in aggressive behavior or
      became more aggressive. The results of the study is powerful evidence of the
      efficacy of the non-confrontational behavior modification program.

PMID- 9192363
TI  - Serum concentration of circulating immune complexes in cats infected with feline
      immunodeficiency virus detected by immune adherence hemagglutination method.
AB  - Circulating immune complexes (CIC) in the sera from 45 clinically healthy cats
      and 23 feline immunodeficiency virus (FIV) infected cats were measured by an
      immune adherence hemagglutination (IAHA) method. The level of CIC in the sera
      from FIV sera-negative healthy cats was 47.2 +/- 47.3 micrograms/ml when
      expressed as heat aggregated feline IgG equivalent value in IAHA reactivity. On
      the other hand, the level of CIC in the sera from FIV infected cats was 757.4 +/-
      910.5 micrograms/ml, which was significantly higher than that of healthy ones.
      CIC levels of 11 symptomatic cats and 12 asymptomatic ones were 837.8 +/- 1138.2
      micrograms/ml and 683.0 +/- 684.2 micrograms/ml, respectively. These results
      showed that IAHA method was reliable to detect CIC levels of cat sera and that
      CIC levels in the sera of cats infected with FIV were higher than those of
      healthy ones.

PMID- 9192365
TI  - A novel developmental process of intestinal epithelial lesions in a calf infected
      with attaching and effacing Escherichia coli.
AB  - A comparative study on the adhesion of attaching and effacing Escherichia coli
      (AEEC) to the enterocytes between the colon of a calf and the jejunum of a piglet
      showed differences in the developmental process of attaching and effacing (AE)
      lesions. In the calf, pedestals consisted of fused microvilli, while in the
      piglet they developed from the apical epithelial cell membranes after effacing
      microvilli. Microvilli adjacent to the AEEC attachment site were atrophic in the
      calf, whereas they were elongated in the piglet. The production of AE lesions in
      the calf may be indicative of a novel developmental process with AEEC infection.

PMID- 9192367
TI  - Distributions of the cardiac plexuses and ganglia in the Beijing duck.
AB  - Distributions of the cardiac plexuses and cardiac ganglia were gross-anatomically
      and histologically studied in eight Beijing ducks. The cardiac plexuses consisted
      of two components, the cardiac nerve arising from the sympathetic trunk and the
      cranial and caudal cardiac nerves arising from the vagus. Branches of these
      nerves made the cardiac plexuses on the epicardium. The cardiac plexuses could be
      divided into the six plexuses, that is, the right and left coronary plexuses,
      pericardiac transverse sinus plexus, caudal cardiac plexus, and right and left
      superior cardiac plexuses. There were small ganglia in the caudal cardiac plexus
      and the right and left coronary plexuses. These ganglia containing multipolar
      neurons were found like a linking chain in a single nerve.

PMID- 9192366
TI  - Analysis of extracellular matrix proteins in malignant chicken cell lines.
AB  - The adherent chicken cell line, MDCC-MSB1-41C, was highly transplantable and
      metastatic in vivo, compared with the parental non-adherent cell line MDCC-MSB1
      from Marek's disease (MD) lymphoblastoid tumor. For clarification of differences
      in extracellular matrix proteins in MSB1-41C and MSB1 cells, examination was made
      of various components of extracellular matrix proteins. A detachment experiment
      indicated the protein(s) recognizing the Arg-Gly-Asp (RGD) sequence, the minimum
      structure required for recognition by the cell-surface receptors, is essential
      for the adherent character. Immunoblot assay using antibodies showed increased
      expression of fibronectin, fibronectin receptors, and vinculin on MSB1-41C cell
      lines. RGD-directed integrins mediate important cell-cell adhesive interaction
      and these interactions with extracellular matrix proteins may thus possibly be
      requisite for migration, proliferation and metastatic dissemination of MDCC-MSB1
      41C cells. The RGD-containing peptide in the culture medium could cause
      detachment of cultured adhesive lymphoid leukosis LSCC-1104X5 cells from the dish
      too.

PMID- 9192368
TI  - Effects of soft X-ray irradiation on NK cell activity and the percentage of
      asialo GM1-positive cells in spleen cells of mice.
AB  - Effects of soft X-ray irradiation on the natural killer (NK) cell activity and
      the percentage of asialo GM1-positive cells of spleen cells in mice were
      investigated by using a soft X-ray generator intended for non-destructive
      radiological examination. Soft X-ray irradiation in graded doses of more than
      25.8 mC/kg indicated dose dependent reductions in the NK cell activity in the
      spleen of irradiated mice. Significant reductions in the population of asialo GM1
      positive cells in spleen cells were also observed. These results suggest that a
      soft X-ray generator could also be useful in immuno-irradiation studies.

PMID- 9192369
TI  - Expression of envelope protein (E2) of bovine viral diarrhea virus in insect
      cells.
AB  - The gene encoding the envelope glycoprotein (E2) of bovine viral diarrhea virus
      (BVDV) was expressed in a baculovirus. The expressed protein was detected on the
      surface of infected cells by immunofluorescence. Western blotting analysis showed
      the presence of the expressed protein of a similar molecular size to the E2
      protein. The antigenicity of expressed protein were tested in guinea pigs and
      cattle. The immunized animals developed neutralizing antibodies against BVDV.

PMID- 9192370
TI  - A field trial of oil adjuvanten trivalent Actinobacillus pleuropneumoniae
      vaccine.
AB  - The trivalent vaccine of A. pleuropneumoniae serotype 1, 2 and 5 (AP3V) was
      prepared in the oil-in-water type adjuvanten form. At an SPF farm, the vaccinated
      pigs were observed for their antibody response, finishing rate, and lung lesions
      at the time of slaughter and for injection scars. The CF titers against serotype
      1, 2 and 5 started to rise after the second injection, showed the highest titer
      at 30 days after injection and then gradually decreased in vaccinated pigs. The
      finishing rate in the vaccinated group was 91.6% and that in the control group
      immunized with commercial vaccine was 60%. The lungs in the control pigs showed
      severe pneumonia with hyperemia, pleural adhesion and abscess. In contrast,
      vaccinated pigs showed slight pneumonia. Injection scars were not observed in
      vaccinated pigs 100 days after the second injection. In conclusion, the pigs
      immunized with AP3V were sufficiently protected against A. pleuropneumoniae
      infection and the trial proved to be satisfactory in the safety of the vaccine
      under field conditions.

PMID- 9192371
TI  - Review on traumatic subarachnoid hemorrhage.
AB  - Recent studies demonstrated clinical significance of the presence of traumatic
      subarachnoid hemorrhage (tSAH) on the initial CT-scan after head injury.
      Investigations show similarities between traumatic and aneurysmal SAH suggesting
      that a similar therapeutic approach as used in spontaneous SAH patients might be
      beneficial in tSAH patients. Evidence of the clinical significance of the finding
      of tSAH on CT after head injury and the beneficial use of the calcium antagonist
      nimodipine in tSAH patients are reported.

PMID- 9192372
TI  - Brain tissue pO2-monitoring in comatose patients: implications for therapy.
AB  - Monitoring of brain tissue partial pressure of O2 (ti-pO2) is a promising new
      technique that allows early detection of impending cerebral ischemia in brain
      injured patients. The purpose of this study was to investigate the effects of
      standard therapeutic interventions used in the treatment of intracranial
      hypertension in comatose patients on cerebral oxygenation. In the neurosurgical
      intensive care unit ti-pO2, arterial blood pressure, intracranial pressure (ICP),
      cerebral perfusion pressure (CPP) and jugular bulb oxygen saturation (SjvO2) were
      prospectively studied (0.1 Hz acquisition rate) in 23 comatose patients (21 with
      severe traumatic brain injury, 2 with intracerebral hematoma) during various
      treatment modalities: elevation of CPP with dopamine (n = 35), lowering of the
      head (n = 22), induced arterial hypocapnia (n = 13), mannitol infusion (n = 16),
      and decompressive craniotomy (n = 1). Ischemic episodes ('IE' = ti-pO2 < 10 mmHg
      for > 15 min) within the first week after the insult were always associated with
      unfavorable neurological outcome. Elevation of CPP from 32 +/- 2 to 67 +/- 4 mmHg
      significantly improved ti-pO2 by 62% (13 +/- 2 to 21 +/- 1 mmHg) and reduced ICP
      indicating intact cerebral autoregulation. Further raising CPP from 68 +/- 2 to
      84 +/- 2 mmHg did not alter ti-pO2. Mannitol-induced ICP reduction from 23 +/- 1
      to 16 +/- 2 mmHg did not affect ti-pO2, nor did lowering of the head from 30
      degrees to 0 degree. Hyperventilation from an endtidal pCO2 of 29 +/- 3 to 21 +/-
      3 mmHg normalized ICP and CPP, but significantly reduced ti-pO2 from 31 +/- 2 to
      14 +/- 3 mmHg. Decompressive craniotomy in a 15-year old patient with refractory
      intracranial hypertension instantly restored ti-pO2. Based on the present data,
      our understanding of many interventions previously believed to improve brain
      oxygenation might have to be re-evaluated. A CPP > 60 mmHg emerges as the most
      important factor determining sufficient brain tissue pO2. Any intervention used
      to further elevate CPP does not improve ti-pO2, to the contrary, hyperventilation
      even bears the risk of inducing brain ischemia.

PMID- 9192373
TI  - Brain tissue pO2-monitoring: catheterstability and complications.
AB  - The authors report on the stability and complications of 73 LICOX brain ti-pO2
      microcatheters in 70 patients. Mean monitoring time was 7.5 +/- 4.0 days.
      Patients prone to cerebral hypoxia (after severe head injury (GCS < 9) or a
      subarachnoid hemorrhage) had a ti-pO2-microcatheter inserted next to the ICP
      probe in the typical frontal position. After the first 15 insertions, instead of
      the 3-way-screw (needing a 6 mm burrhole), a 1-way-screw (needing a 2.7 mm
      burrhole) was used for fixation in the bone; by doing so, the procedure can be
      performed in the ICU and takes only 15 min. Whenever possible a calibration at
      room air (to determine the sensitivity-drift) and in oxygen free solution (to
      determine the zero-drift) was performed after removal of the catheters. Ideally
      the expected pO2 at room air was around 154 mmHg (temperature dependent) and at
      zero calibration 0 mmHg. Mean sensitivity-drift for 54 catheters was -8.5 +/-
      15.4%. Dividing the catheters into groups, depending on the duration of
      monitoring (1-4, 5-8 and 9-16 days), revealed that the greatest part of the
      (negative) sensitivity-drift occurred during day 1-4 after insertion. After 1
      week of monitoring sometimes a positive drift occurred (being far less than the
      negative drift during the first 4 days). Compared to the old catheters (-10.3 +/-
      17.3%) (on the first half of the patients) the new ones showed a lower
      sensitivity-drift (-6.8 +/- 13.4%). The zero-drift of 56 catheters was low with
      mean drift after 7.5 +/- 4.0 days of 1.5 +/- 1.5 mmHg. Here also the highest
      drift occurred on day 1-4 after insertion. No infection was seen and 2 times
      (2.7%) a small hematoma, not needing evacuation occurred. As the ti-pO2-catheter
      (having a smaller diameter) and the ICP-catheter were inserted at the same time,
      one cannot distinguish which catheter caused the hematoma. A possible explanation
      for the occurrence of the two hematomas is the insertion of the catheters too
      close to the midline. The authors conclude that LICOX ti-pO2-monitoring is a safe
      and reliable method. Further decrease of the complication rate and increase of
      the catheter-stability may be expected.

PMID- 9192374
TI  - Dynamic changes of cerebral oxygenation measured by brain tissue oxygen pressure
      and near infrared spectroscopy.
AB  - The aim of this study was to find out whether a correlation exists between
      changes in brain tissue oxygen pressure (ti-pO2) and hemoglobin oxygenation
      (HbO2) measured by near-infrared spectroscopy. We studied 10 patients with severe
      head injury. A ti-pO2 monitoring device was introduced in the frontal white
      matter as soon as possible after administration. Additionally a NIRS sensor was
      placed at the forehead. All data were recorded simultaneously. Changes of the ti
      pO2 curve were defined as events with the following criteria: > 10% change from
      the baseline value, > 3 min duration, clearly not an artifact. 137 events were
      found with a mean change of ti-pO2 of 8.3 +/- 10.2 mmHg. In 77.4% we observed a
      corresponding change of the HbO2. In 7 patients we found a good correlation (r >
      0.7) between change ti-pO2 and change HbO2. In 3 patients the correlation was
      poor. The reason for poor correlation might be poor signal quality of the NIRS
      sensor or inhomogenous distribution of ischemic areas in the whole brain. We
      conclude that under the condition of a stable NIRS signal and a diffuse brain
      lesion, changes of ti-pO2 are well reflected by NIRS.

PMID- 9192376
TI  - Role of fibroblast growth factors in neural trauma.
AB  - Following a traumatic insult to the adult mammalian central nervous system (CNS),
      a complex of molecular and cellular responses ensues. Several peptide growth
      factors seem implicated in the CNS traumatic response. Furthermore, several of
      them, like some of the members of the fibroblast growth factor family of
      polypeptides seem to have a protective role. The purpose of this article is to
      point toward some basic aspects of FGFs neuroprotective activity against
      traumatic CNS injuries for the development of novel therapeutic strategies in
      neural trauma.

PMID- 9192375
TI  - Influence of body position on tissue-pO2, cerebral perfusion pressure and
      intracranial pressure in patients with acute brain injury.
AB  - It is a common practice to position head-injured patients in bed with the head
      elevated above the level of the heart in order to reduce intracranial pressure
      (ICP). This practice has been in vivid discussion since some authors argue a
      horizontal body position will increase the cerebral perfusion pressure (CPP) and
      therefore improve cerebral blood flow (CBF). However, ICP is generally
      significantly higher in the horizontal position. The aim of this study was to
      evaluate changes in regional microcirculation using tissue pO2 (ti-pO2), as well
      as changes in cerebral perfusion pressure (CPP) and intracranial pressure induced
      by changes in body position in patients with head injury. The effect of 0 degree
      and 30 degrees head elevation on ti-pO2. CPP, ICP and arterial blood pressure
      (MABP) was studied in 22 head injured patients during day 0-12 after trauma. The
      mean ICP was significantly lower at 30 degrees head elevation than at 0 degree
      (14.1 + 8.6 vs. 19.9 + 8.3 mmHg). While MABP was unaffected by head elevation,
      CPP was slightly higher at 30 degrees than at 0 degree (76.5 + 13.5 vs. 71.5 +
      13.2 mmHg). However, regional ti-pO2 was unaffected by body position (30 degrees
      vs. 0 degree: 24.9 + 13.1 vs. 24.7 + 12.9 mmHg). In addition, there was no change
      in the time course after trauma concerning these findings in the individual
      patients. The data indicate that a moderate head elevation of 30 degrees reduces
      ICP without jeopardizing regional cerebral microcirculation as monitored using a
      polarographic ti-pO2 microcatheter.

PMID- 9192377
TI  - Early dynamics of acute extradural and subdural hematomas.
AB  - In a retrospective study volumes of 42 extradural and 102 subdural traumatic
      hematomas were evaluated. Results were related with the time interval between
      injury and initial CT scan, outcome, coma grade and subject age. Mean volumes
      were found to increase with time after the injury. In the first hour volumes of 8
      intracranial hematomas were hardly space consuming, while they became clearly
      space consuming in the second and in later hours after the injury. It was
      therefore concluded that it should not take longer than one hour until a CT scan
      be performed when an intracranial post-traumatic hematoma is suspected in the
      comatose patient.

PMID- 9192378
TI  - Traumatic brain injury registry in Taiwan.
AB  - This project was designed to examine the epidemiology of traumatic brain injury
      (TBI) in Taiwan. A total of 58,563 cases of TBI was collected from 114 hospitals
      in Taiwan during the period July 1, 1988-June 30, 1994. Traffic accident was the
      major cause of TBI (69.4%), followed by falls and assaults. Motorcyclists
      accounted for the vast majority of TBI cases among traffic accident victims
      (64.5%). The Glasgow Coma Scale was used in assessing the severity. 41,646 cases
      (79.5%) were considered mild, 4,637 cases (8.9%) moderate, and 6,078 cases
      (11.6%) severe. Skull x-ray showed fracture in 7,663 cases (14.6%). Intracranial
      hemorrhage was identified in 28.6% of patients receiving CT scanning. Craniotomy
      was performed in 5,226 cases (9%). The outcome of TBI was determined by the
      Glasgow Outcome Scale. Death occurred in 2,621 cases (5.4%), vegetative state in
      429 cases (0.9%), severe disability in 1,293 cases (2.6%), moderate disability in
      1,890 cases (3.9%), and good recovery in 42,596 cases (87.2%). The severity and
      outcome were worse than those of Western reports. In order to alleviate this
      problem, a helmet use persuasion program was conducted by the Police Department
      in Taipei City from January to June, 1994. Results of this program showed a
      significant reduction of TBI-related hospitalization, severity and fatality
      during this period of intervention. This study points out the seriousness of TBI
      in Taiwan and suggests some approaches and priorities for prevention.

PMID- 9192379
TI  - Multiparametric continuous monitoring of brain metabolism and substrate delivery
      in neurosurgical patients.
AB  - Brain function and tissue integrity are highly dependent on continuous oxygen
      supply and clearance of CO2. Aerobic metabolism is the major energy source to
      normal brain, however, during hypoxia and ischemia, lactate accumulation may
      sometimes be seen, indicating anaerobic glycolysis after severe head injury.
      Current monitoring techniques often fail to detect such events which can affect
      substrate delivery to the injured brain. We have recently adapted a method for
      continuous monitoring of brain tissue pO2, pCO2, pH and temperature, using a
      single sensor. The multiparameter sensor is inserted into brain tissue, via a new
      three lumen bolt, together with a standard ventriculostomy catheter and a
      microdialysis probe. The system has been left in place as long as needed, but
      never more than 7 days. All readings were compared to clinical parameters, and
      outcome. Stable measurements could be obtained in the first group of 20 patients,
      after calibration and rigid fixation, using the new bolt. Severely head injured
      patients had brain oxygen levels of less than 25-30 mmHg for the first hours
      after injury. Thereafter two patterns could be seen. Patients with favorable
      outcome had a slow increase in brain oxygen, and brain CO2 decreased to normal
      values, as long as the cerebral perfusion pressure (CPP) was kept above 70 mmHg.
      However, in those patients with secondary ischemic events, and bad outcome, a
      further decline in brain oxygen to anaerobic levels (< 20 mmHg) was seen. For
      these patients, both decreased and increased brain CO2 levels could be seen.
      Brain CO2 levels of 90-150 mmHg were consistently seen after brain death. Brain
      pH was inversely related to brain CO2 for all patients. Brain glucose and lactate
      in patients with poor outcome were 639 microM l-1 +/- 330, and 1642 microM l-1 +/
      788, whereas patients with good outcome had brain glucose levels of 808 microM l
      1 +/- 321 and lactate levels of 1001 microM l-1 +/- 417. Extended neuromonitoring
      using a combined sensor for brain oxygen, CO2, pH and temperature measurements,
      as well as a microdialysis probe for glucose and lactate analysis may optimize
      the management of comatose neurosurgical patients in the future, by allowing a
      fuller understanding of dynamic factors affecting brain metabolism.

PMID- 9192380
TI  - Outcome after severe head injury: an analysis of prediction based upon comparison
      of neural network versus logistic regression analysis.
AB  - More reliable prediction of outcome would be helpful for clinicians who treat
      severely head-injured patients. To determine if neural network modeling would
      improve outcome prediction compared with standard logistic regression analysis
      and to determine if data available 24 h after severe head injury allows better
      prediction than data obtained within 6 h, we tested the ability of both
      techniques at these two times to predict outcome (dead versus alive) at 6 months.
      One thousand sixty-six consecutive patients with Glasgow Coma Scale scores of 8
      or less during the first 24 h after injury were randomly divided into two groups.
      Data from the first group (n = 799) were used to develop the models; data from
      the second group (n = 267) were used to test the accuracy, sensitivity, and
      specificity of the models by comparing predicted and actual outcomes. The 6-month
      mortality rate was 63.5%. Our findings confirm the importance of age, Glasgow
      Coma Scale scores, and hypotension in predicting outcome. Using data available at
      24 h improved the predictive power of both models compared with admission data;
      at both time points, however, the differences in the results obtained with the
      two models were negligible. We conclude that outcome (dead versus alive) at 6
      months after severe head injury can be predicted with logistic regression or
      neural network models based on data available at 24 h. Critical therapeutic
      decisions, such as cessation of therapy, should be based on the patient's status
      1 day after injury and only rarely on admission status alone.

PMID- 9192381
TI  - Microdialysis in the human brain: review of its applications.
AB  - The analysis of brain extracellular fluid can provide essential information about
      both the physiology and the pathology of the human nervous system. The
      introduction of microdialysis into the clinical sciences has provided a new
      opportunity to study this environment. Using microdialysis, endogenous substances
      can be obtained and drugs can be delivered in very close proximity to the
      receptors and ion channels on neuronal membranes. In this sense, microdialysis
      can be regarded as a novel technique since it can continuously measure
      interstitial brain activity in living tissue while causing minimal adverse
      effects. Although it has been well established as an experimental technique for
      neurochemistry, the true utility of microdialysis as a clinical tool is still
      being defined. The potential clinical applications of microdialysis to
      characterize the human brain extracellular environment in patients with
      pathologic conditions has grown rapidly. The number of publications in which
      microdialysis has been performed in clinical studies has been increasing during
      recent years and this article gives a summary of those reports where
      microdialysis was applied in the study of human brain disorders.

PMID- 9192382
TI  - Effect of a single huge dose of methylprednisolone on blood flow, evoked
      potentials, and histology after acute spinal cord injury in the rat.
AB  - Effects of a single, huge dose of methylprednisolone on post-traumatic spinal
      cord blood flow (SCBF), evoked potentials and histological changes were studied
      in a rat model of spinal cord injury. The purpose of this study was to assess the
      optimal dose of methylprednisolone for the treatment of rat spinal cord injury.
      Twenty-five male Wistar rats were subjected to an acute clip compression injury
      at 51 g for 1 min at C8-T1, and then received an intravenous bolus injection of
      one of the following 30 min after injury: vehicle, 30, 60, 120 or 240 mg kg-1
      methylprednisolone. SCBF was measured at the injury site and an adjacent area
      with the hydrogen clearance technique. Sensory evoked potentials following
      sciatic stimulation were recorded from the somatosensory and cerebellar cortices.
      Descending volleys were recorded from T9-10 spinal cord following cerebellar
      stimulation. SCBF and evoked potential recordings were repeated until perfusion
      fixation at 4 h after injury. After injury, SCBF at both levels significantly
      dropped, and all evoked potentials disappeared in all animals. None of the doses
      of methylprednisolone improved post-traumatic SCBF, or evoked potentials.
      Quantitative histological assessment of the injured cords revealed no significant
      differences in hemorrhages or cavitation in the spinal cord among the treatment
      groups. This study showed that a single huge dose of methylprednisolone from 30
      to 240 mg kg-1 had no beneficial effects on the traumatized rat spinal cord in
      the acute stage.

PMID- 9192383
TI  - Effect of VA-045, a novel apovincaminic acid derivative, on closed head injury
      induced neurological dysfunction in aged rats.
AB  - Effects of VA-045, a novel apovincaminic acid derivative, on behavioral outcome
      following closed head injury (CHI) were examined in aged (21-28 months) rats. CHI
      was induced by dropping a 400 g weight through a tube from 150 cm above a steel
      helmet placed on the vertex. Beam balancing latency, neurological deficits and
      body weight were recorded before CHI and for up to 14 days after CHI. When
      compared with the sham group, all measurements of parameters of behavioral
      outcome in the CHI group were significantly worsened after CHI. Intraperitoneal
      administration of VA-045 (1 and 3 mg kg-1) or thyrotropin-releasing hormone (TRH,
      10 mg kg-1) and vehicle was started 24 h after CHI, and continued once daily for
      13 days. VA-045 but not TRH significantly overcame the CHI-induced neurological
      deficits, shortened the latency of beam balancing and decreased body weight loss.
      VA-045 may prove useful for treating aged patients with disturbances of
      consciousness or motor deficits after CHI.

PMID- 9192384
TI  - Clinical predictors of the psychosocial long-term outcome after brain injury.
AB  - The correlation of clinical with psychological and social data is an attempt to
      find predictors of the definite long-term outcome after brain injury. 34 patients
      were reexamined 3 to 8 years after the accident using a number of psychological
      tests. Additionally, life quality was defined and evaluated. Only patients with
      an initial Glasgow Coma Scale-Score of 3-12, an intracranial traumatic lesion on
      computertomography and age 16-65 years at the time of accident were included in
      this study. Patients exhibited a uniform pattern of disturbances in psychosocial
      long-term outcome. These disturbances were compared with initial clinical data:
      memory, attention and learning were significantly correlated with the duration of
      coma and the presence of additional extracerebral injuries. From the initial
      computerized tomography, the findings 'compression of basal cisterns' and
      'intracerebral contusion' showed to be predictors of the cerebral function. Late
      social status and behavior, defined as quality of life, were clearly related with
      initial clinical findings. In conclusion, there are early clinical predictors of
      the long term social and psychological outcome after brain injury.

PMID- 9192385
TI  - Post-cranioplasty cerebrospinal fluid hydrodynamic changes: magnetic resonance
      imaging quantitative analysis.
AB  - The syndrome of the trephined has been described in many patients with cranial
      defects as an indication for cranioplasty. Cerebral blood flow changes, the
      effect of the atmospheric pressure on the brain, as well as cerebrospinal fluid
      hydrodynamic changes have been postulated as the possible reasons for this
      syndrome. Using dynamic phase-contrast magnetic resonance imaging we measured
      arterial, venous, and cerebrospinal fluid flow into and out of the skull, before
      and after cranioplasty in one patient whose bone flap was removed because of
      osteomyelitis. We report significant changes in the oscillatory CSF flow after
      cranioplasty. A moderate increase in venous outflow as well as a two-fold
      increase in craniocaudal cerebrospinal fluid systolic flow velocity was measured
      after the skull closure. The changes in the cerebrospinal fluid oscillatory flow
      at the level of the craniovertebral junction could reflect changes in the
      compliance of the craniospinal system produced by closure of the cranial defect.

PMID- 9192386
TI  - Neurotraumatology: ultrasonic evaluation of the central nervous system.
AB  - In this study we describe the technique of intraoperative ultrasound imaging of
      brain and spinal cord in trauma patients. The images are shown and their
      interpretation is discussed. This intraoperative imaging allows for localization
      of hematomas, bone fragments and indriven foreign bodies (i.e., pieces of
      plastic, glass, metal, etc.). Disc material and bone fragments deep to the spinal
      cord can be localized with this technique. Real-time ultrasound can be used to
      guide instruments within the brain and, thereby, provide dynamic guidance for
      removal of bone fragments and foreign bodies dynamically. In summary,
      intraoperative real-time ultrasonic imaging is of use to the neurosurgeon in the
      treatment of the neurotrauma patient.

PMID- 9192387
TI  - Transcutaneous functional neuromuscular stimulation of certain traumatic complete
      thoracic paraplegics for independent short-distance ambulation.
AB  - The paper describes a system for transcutaneous functional neuromuscular
      stimulation (FNS) of certain traumatic thoracic-level complete paraplegics for
      independent unbraced short distance ambulation. The system described has been
      approved by the FDA in 1994 for that purpose. Its design, control, operation
      principles and parameters are described. Patient acceptance criteria and
      contraindications are outlined as is patient's training. Ambulation results are
      discussed and clinical and medical observations are reviewed. Finally general
      comments are made on the system's shortcomings and on possible improvements.

PMID- 9192388
TI  - Mitochondrial dysfunction after experimental and human brain injury and its
      possible reversal with a selective N-type calcium channel antagonist (SNX-111).
AB  - We have recently demonstrated in a rat model that traumatic brain injury induces
      perturbation of cellular calcium homeostasis with an overload of cytosolic
      calcium and excessive calcium adsorbed on the mitochondrial membrane,
      consequently the mitochondrial respiratory chain-linked oxidative phosphorylation
      was impaired. We report the effect of a selective N-type calcium channel blocker,
      SNX-111 on mitochondrial dysfunction induced by a controlled cortical impact.
      Intravenous administration of SNX-111 at varying times post injury was made. The
      concentration titration profile revealed SNX-111 at 4 mg kg-1 to be optimal, and
      the time window to be administration at 4 h post-injury, in line with that
      reported on the effect of SNX-111 in experimental stroke. Under optimal
      conditions, SNX-111 significantly improved the mitochondrial respiratory chain
      linked functions, such as the electron transfer activities with both succinate
      and NAD-linked substrates, and the accompanied energy coupling capacities
      measured as respiratory control indices (RCI) and ATP synthesis (P/O ratio), and
      the energy linked Ca2+ transport. In order to assess the applicability of these
      data to the clinical setting, we have initiated studies with brain tissue which
      has to be resected during surgical treatment. Five patients suffered from brain
      trauma, one from intracranial hypertension due to stroke (noninfarcted tissue was
      taken), and one from epilepsy. Our data revealed that brain mitochondria derived
      from the patient with intracranial hypertension and the patient with epilepsy
      were tightly coupled with good respiratory rates with glutamate and malate as
      substrates, and high P/O ratios. The rates of respiration and ATP synthesis were
      severely impaired in the brain mitochondria isolated from traumatized patients.
      These results indicate that investigation of brain mitochondrial functions can be
      used as a measure for trauma-induced impairment of brain energy metabolism. The
      time window for the effect of SNX-111 in mitochondrial function and the
      (preliminary) similarity between mitochondrial dysfunction in experimental
      animals and humans make the drug appear to be well suited for clinical trials in
      severe head injury.

PMID- 9192389
TI  - Computer simulation of neuronal toxicity in the spinal cord.
AB  - The use of computers to model biological systems is a relatively new research
      tool. For example, it is possible to write mathematical systems to model neuronal
      activity involved in memory and learning and to model blood flow in any organ
      such as the brain. There is also an interest in designing computer-controlled
      machines to simulate human activities such as hand movements and vision. One of
      the most important uses of computer modeling is as a research tool to test
      hypotheses and aid in formulating new hypotheses. This enables the investigator
      to apply preliminary tests on several experimental strategies and select for
      animal experimentation the ones that are most likely to produce unambiguous and
      interpretable results. In the following article, we describe a computer model of
      neuron toxicity in the mammalian spinal cord.

PMID- 9192390
TI  - Dietary intake in relation to restrained eating, disinhibition, and hunger in
      obese and nonobese Swedish women.
AB  - The aims of this study were to: describe dietary intakes of obese and nonobese
      middle-aged women using a validated food frequency questionnaire; to assess
      dietary restraint, disinhibition, and hunger by the three factor eating
      questionnaire (TFEQ) in obese and nonobese samples and determine which of the
      factors are independently associated with obesity; and to examine correlations
      between selected nutritional variables and the TFEQ factors. Subjects studied
      included 179 obese Swedish women (BMI > 32) and 147 nonobese population-based
      controls (BMI < 28). Age-adjusted mean energy intake was significantly higher in
      obese women (2730 +/- 78 vs. 2025 +/- 85 kcal, p < 0.0001). In absolute and
      relative terms, fat intake was higher and alcohol intake was lower in the obese
      subjects. Disinhibition was the strongest TFEQ factor independently
      differentiating the obese and nonobese states, i.e., after adjustment for
      restraint and hunger. Within the obese sample, strong associations were seen
      between energy intake and disinhibition (p = 0.0005) and hunger (p = 0.0004). The
      association between energy intake and restrained eating was negative and weaker
      (p = 0.04). No such associations were seen in nonobese women. Thus, using a
      dietary instrument that is valid and unbiased with respect to obesity, strong
      psychological correlates, possibly causal, of variability in energy intake were
      detected in middle-aged women with obesity. Disinhibition is associated with both
      obesity and high-energy intakes and is therefore an important factor to consider
      in the treatment of women with obesity.

PMID- 9192391
TI  - Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP)
      and electrophoretic assays for the mouse obese (Lepob) mutation.
AB  - Three polymerase chain reaction-based assays for the mouse Lepob mutation are
      described: Dde I site created by the C-->T transversion characterizing Lepob
      enables positive detection of the mutant allele; positive detection of the wild
      type Lep allele is achieved by the use of primer sequence which introduces an A-
      >C substitution, creating an Msp I site in the normal allele; and an
      electrophoretic assay which positively identifies the heterozygote.

PMID- 9192392
TI  - Abdominal visceral fat is associated with a BclI restriction fragment length
      polymorphism at the glucocorticoid receptor gene locus.
AB  - Several investigations have suggested that body fat distribution is influenced by
      nonpathologic variations in the responsiveness to cortisol. Genetic variations in
      the glucocorticoid receptor (GRL) could therefore potentially have an impact on
      the level of abdominal fat. A restriction fragment length polymorphism (RFLP) has
      previously been detected with the BclI restriction enzyme in the GRL gene
      identifying two alleles with fragment lengths of 4.5 and 2.3 kb. This study
      investigates whether abdominal fat areas measured by computerized tomography (CT)
      are associated with this polymorphism in 152 middle-aged men and women. The less
      frequent 4.5-kb allele was found to be associated with a higher abdominal
      visceral fat (AVF) area independently of total body fat mass (4.5/4.5 vs. 2.3/2.3
      kb genotype; men: 190.7 +/- 30.1 vs. 150.7 +/- 33.3 cm2, p = 0.04; women: 132.7
      +/- 37.3 vs. 101.3 +/- 34.5 cm2, p = 0.06). However, the association with AVF was
      seen only in subjects of the lower tertile of the percent body fat level. In
      these subjects, the polymorphism was found to account for 41% (p = 0.003) and 35%
      (p = 0.007), in men and women, respectively, of the total variance in AVF area.
      The consistent association between the GRL polymorphism detected with BclI and
      AVF area suggests that this gene or a locus in linkage disequilibrium with the
      BclI restriction site may contribute to the accumulation of AVF.

PMID- 9192393
TI  - The effect of dietary energy restriction on body weight gain and the development
      of noninsulin-dependent diabetes mellitus (NIDDM) in Psammomys obesus.
AB  - Food intake was restricted to 75% of ad libitum levels in 37 male Psammomys
      obesus (Israeli Sand Rats) from the ages of 4 (weaning) to 10 weeks. Energy
      restriction reduced the mean bodyweight at 10 weeks by 29% compared with 44 ad
      libitum fed controls. Hyperglycemia was prevented completely in the food
      restricted group, and mean blood glucose concentrations were significantly
      reduced (3.8 +/- 0.2 vs. 5.5 +/- 0.4 mumol/L; p < 0.05) compared with control
      animals. Plasma insulin concentrations were also decreased significantly compared
      with ad libitum fed controls (105 +/- 13 vs. 241 +/- 29 mU/L; p < 0.05). Although
      energy restriction prevented hyperglycemia from developing in 10-week-old P.
      obesus, 19% of the food restricted animals still developed hyperinsulinemia. We
      concluded that hyperphagia between the ages of 4 to 10 weeks may be essential for
      the development of noninsulin-dependent diabetes mellitus in P. obesus, but that
      hyperinsulinemia may still occur in the absence of hyperphagia and hyperglycemia,
      suggesting a significant genetic influence on the development of hyperinsulinemia
      in this animal model.

PMID- 9192394
TI  - Location and effect of obesity on putative anorectic binding sites in the rat
      brain.
AB  - Anorectic drugs such as mazindol bind to a class of low-affinity, sodium
      sensitive sites in the brain which are affected by ambient glucose concentrations
      and a predisposition to develop diet-induced obesity (DIO). This study used
      quantitative autoradiography of 10 nM 3H-mazindol binding to identify the
      cellular location of these putative anorectic binding sites in the brain and to
      assess the way in which the development of DIO affected their binding. We
      previously showed that chow-fed, obesity-prone rats have widespread increases in
      brain 3H-mazindol binding to these low-affinity sites as compared with diet
      resistant (DR) rats. Here, low-affinity 3H-mazindol binding was assessed in the
      brains of eight rats which developed DIO vs. eight which were DR after three
      months on a high-energy diet. DIO rats gained 89% more weight and had 117% higher
      plasma insulin levels but no difference in plasma glucose levels compared with DR
      rats. Along with these differences, low-affinity 3H-mazindol binding in DIO rats
      was identical to that in DR rats in all of the 23 brain areas assessed. This
      suggested that this binding was downregulated by the development of obesity in
      DIO rats. In other chow-fed rats, stereotaxic injections of 5,7
      dihydroxytryptamine and 6-hydroxydopamine (6OHDA) to ablate serotonin and
      catecholamine nerve terminals in the ventromedial nucleus of the hypothalamus
      (VMN) had no effect on 3H-mazindol binding. However, ibotenic acid injected into
      the VMN, substantia nigra, pars reticulata, and pars compacta destroyed intrinsic
      neurons and/or their local processes and decreased low-affinity 3H-mazindol
      binding by 13%-22%. Destruction of dopamine neurons in the substantia nigra, pars
      compacta, and noradrenergic neurons in the locus ceruleus with 6OHDA also reduced
      3H-mazindol binding in those areas by 9% and 12%, respectively. This suggested
      that up to 22% of putative anorectic binding sites may be located on the cell
      bodies of dopamine, norepinephrine, and other neurons, but not on serotonin or
      catecholamine nerve terminals in the brain. Binding to these sites may be
      downregulated by the development of DIO, possibly as a result of the concomitant
      hyperinsulinemia.

PMID- 9192395
TI  - Differences in binding of hepatic nuclear proteins from lean and obese rats to
      the 5'-upstream region of tyrosine aminotransferase.
AB  - The glucocorticoid effects on liver tyrosine aminotransferase mRNA levels have
      been studied in young, lean, and obese Zucker (fa/fa) rats and 5'-upstream
      regions of the tyrosine aminotransferase (TAT) gene have been used in gel
      retardation studies to investigate nuclear protein binding. Hepatic TAT mRNA
      levels were increased in obese fa/fa rats but were normalized seven days after
      adrenalectomy. Corticosterone replacement to adrenalectomized rats restored the
      increased levels of TAT mRNA in the obese animals. A 60-bp fragment of upstream
      TAT DNA (-2463 to -2403) was identified which showed higher levels of band
      shifting after incubation with hepatic nuclear proteins of obese rats compared
      with the proteins from lean animals. This differential level of gel retardation
      was substantially reduced by alkaline phosphatase treatment of nuclear proteins.
      Gel retardation was reduced when nuclear proteins were prepared from
      adrenalectomized obese rats, and increased with nuclear proteins from
      adrenalectomized rats replaced with corticosterone. DNA affinity chromatography
      and gel electrophoresis identified three proteins of approximately 58, 62, and 65
      kDa in the DNA-protein complex. Increased amounts of these three proteins were
      purified from nuclei of obese rats. HNF3 alpha antibodies induced hypershift of
      the gel retardation pattern implicating HNF3 alpha as one of the proteins that
      binds to the 60 bp DNA fragment. The data support the hypothesis that decreased
      phosphorylation of nuclear proteins in obese rats is glucocorticoid-dependent and
      may contribute to the altered transcriptional activity of glucocorticoid
      responsive genes.

PMID- 9192396
TI  - Lifestyle modification in the pharmacologic treatment of obesity: a pilot
      investigation of a potential primary care approach.
AB  - This study examined a new method of providing brief, individual lifestyle
      modification to obese individuals treated by pharmacotherapy. Twenty-six women
      with a mean (+/- SD) age of 47.0 +/- 7.2 years, weight of 97.6 +/- 13.0 kg, and
      body mass index of 36.5 +/- 5.0 kg/m2 were prescribed 60 mg/d of fenfluramine and
      15 mg/d of phentermine for one year. In addition, half of the women were randomly
      assigned to traditional group behavior modification, conducted by a nutritionist,
      which included 32 75-minute sessions during the year. The other half were
      provided lifestyle modification by a physician during 10 15-20 minute structured
      visits. All participants received identical treatment manuals and comparable
      assignments for behavior change. At the end of one year, patients in the
      physician group achieved the same highly successful weight losses as those
      treated by group behavior modification (13.9 +/- 9.6 kg vs. 15.4 +/- 7.9 kg,
      respectively). Treatment was associated with highly significant improvements in
      lipids and lipoproteins, as well as in mood and several measures of appetite.
      Weight loss the first four weeks, as well as patient completion of daily food
      records during the first 18 weeks, correlated positively with weight loss at
      weeks 18, 26, and 52. Results of this study await replication using larger
      samples but strongly suggest that effective lifestyle modification can be
      provided during brief, structured physician visits. The findings are discussed in
      terms of their implications for the treatment of obesity in primary care
      practice.

PMID- 9192397
TI  - Comparison of attitudes and behaviors related to nutrition, body size, dieting,
      and hunger in Russian, black-American, and white-American adolescents.
AB  - Attitudes and behaviors related to nutrition are known to differ between white
      American and black-American adolescents, however, little is known about teenagers
      from Russia. We hypothesized that, compared with white-American or black-American
      teenagers, Russian teenagers would prefer a larger body size, be less likely to
      diet, and be less concerned about being overweight. Self-administered
      questionnaires were completed by 196 students in Moscow, 326 white-American, and
      239 black-American adolescents who attended school in North Carolina (mean age =
      16). Ideal body mass index (BMI) was calculated from measured height and the
      response to the question, "What do you consider to be your ideal weight?" Mean
      ideal BMI was higher in black-American boys (25.1) and girls (21.4) than in white
      American boys (22.1) and girls (19.2), and Russian boys (21.8) and girls (19.1).
      After controlling for BMI, black-American girls were less than half as likely to
      report dieting compared with white-American girls. There were no significant
      differences among white-American girls and Russian girls, and there were no
      ethnic differences between boys in the prevalence of dieting. White-American
      girls and black-American girls were much more likely to identify being overweight
      as an important nutritional concern than were Russian girls (odds ratios > 10),
      and there were no ethnic differences among boys. We conclude that preferences for
      body size, the prevalence of dieting, and concerns about being overweight were
      similar in Russian and white-American teens, with the exception of Russian
      teenaged girls who were less likely than American girls to identify being
      overweight as an important concern. Overall, weight-related attitudes and
      behaviors in Russian teenagers were more similar to those of white-American
      teenagers than those of black-American teenagers.

PMID- 9192398
TI  - Psychosocial concerns and health-compromising behaviors among overweight and
      nonoverweight adolescents.
AB  - OBJECTIVE: To compare weight-specific and global psychosocial concerns and health
      compromising behaviors among overweight and nonoverweight youth across gender and
      ethnicity. METHODS: A cross-sectional school-based survey of 31,122 adolescents
      in grades 7 to 12. Based on self-reported heights and weights, respondents were
      categorized as nonoverweight (body mass index (BMI) < 85th percentile),
      moderately overweight (85th percentile < BMI < 95th percentile), or severely
      overweight (BMI > 95th percentile). RESULTS: Global psychosocial concerns, such
      as emotional well-being, suicidal ideation, future job concerns, and peer
      concerns, did not differ greatly between nonoverweight, moderately overweight,
      and severely overweight adolescents. Substance abuse behaviors were equally or
      less prevalent among the overweight group. Overweight girls were significantly
      less likely to consume alcohol, whereas overweight boys were at lower risk for
      marijuana use. In contrast, overweight youth were more likely to perceive their
      health as only fair or poor and were more likely to express weight-specific
      concerns and engage in behaviors such as chronic dieting and binge eating than
      nonoverweight youth. Overweight American Indian girls perceived their physical
      health more positively than nonoverweight American Indian girls. Strong
      associations were found between overweight status and chronic dieting among
      African American boys and girls. CONCLUSIONS: Nutritional counseling and
      educational programs need to address the weight-specific concerns and behaviors
      of overweight adolescents. However, assumptions regarding global psychosocial
      concerns and health-compromising behaviors among overweight adolescents of
      different genders and ethnicities should be avoided. These broad issues need to
      be explored in more depth at both the research and intervention levels.

PMID- 9192399
TI  - Serial measurements of body composition in obese subjects during a very-low
      energy diet (VLED) comparing bioelectrical impedance with hydrodensitometry.
AB  - Bioelectrical impedance analysis (BIA) is a convenient, inexpensive, and
      noninvasive technique for measuring body composition. BIA has been strongly
      correlated with total body water (TBW) and also has been validated against
      hydrodensitometry (HD). The accuracy and clinical utility of BIA and HD during
      periods of substantial weight loss remain controversial. We measured body
      composition in moderately and severely obese patients serially using both methods
      during a very-low-energy diet (VLED). Mean initial weight in these patients was
      116 (+/-30) kg (range, 74-196 kg). Mean weight loss was 24 (+/-13) kg with a
      decrease in fat mass (FM) by HD of kg (p < 0.001) and a decrease in fat-free mass
      (FFM) of 3.6 kg (p < 0.05). Loss of FFM is best predicted by the rate (kg/wk) of
      weight loss (r2 = 0.86, p < 0.0001). FFM, as predicted from BIA equations, was
      highly correlated with FFM as estimated by HD during all testing sessions (r =
      0.92-0.98). Although highly correlated, BIA overestimated FFM relative to HD and
      this difference appeared to be more pronounced for taller patients with greater
      truncal obesity. Although the discrepancy was no greater during weight-loss
      treatment, the level of disagreement was considerable. Therefore, the two methods
      cannot be used interchangeably to monitor relative changes in body composition in
      patients with obesity during treatment with VLED. The discrepancy between BIA and
      HD may be caused by body mass distribution considerations and by perturbations in
      TBW which affect the hydration quotient for FFM (BIA) and/or which affect the
      density constants for FFM and FM (HD).

PMID- 9192400
TI  - Dietary and exercise interventions for juvenile obesity: long-term effect of
      behavioral and public health models.
AB  - We investigated the influence of nutrition and exercise interventions within
      cognitive/behavioral and public health formats on weight and blood lipid profiles
      in obese children. Compliance was also examined as well as the relationship of
      the compliance measures with clinical outcome variables. Three conditions were
      compared over 16 sessions: nutrition and eating-habit change followed by exercise
      (NE), exercise followed by nutrition and eating-habit change (EN), and an
      information control (INFO). NE and EN were presented in a cognitive/ behavioral
      framework which focused on the development of self-regulation whereas the INFO
      condition received the same material in a public health/educational model. NE and
      EN participants evidenced modest, yet significant, reductions in weight and blood
      lipids, and the impact of these two interventions endured at a five-year follow
      up. In contrast, INFO participants displayed stable weight and blood lipids
      during the course of the program, and most remained morbidly obese at follow-up.
      Improved nutrition, increased physical activity and fitness were significantly
      correlated with weight and lipid reductions.

PMID- 9192401
TI  - Aqueduct occlusion does not impair feeding induced by either third or fourth
      ventricle galanin injection.
AB  - Exogenous galanin stimulates feeding when injected into forebrain and hindbrain
      sites, including the third and fourth ventricles (3V and 4V), amygdala,
      paraventricular nucleus of the hypothalamus (PVN), and nucleus of the solitary
      tract (NTS). Because the PVN and NTS border the ventricular space, it is possible
      that feeding stimulated by injection of galanin at these sites may be caused by
      the transport of galanin through the ventricular system to a remote site of
      action. The role of ventricular transport of galanin between the 3V and 4V in
      galanin-induced feeding was examined in this study. Rats were implanted with two
      guide cannula assemblies: one dorsal to the mesencephalic aqueduct and the other
      in the 3V or 4V. Feeding in response to 3V or 4V galanin injection was first
      measured after sham-occlusion of the aqueduct. Subsequently, flow of
      cerebrospinal fluid between the forebrain and hindbrain ventricles was acutely
      interrupted by injection of a silicone grease plug into the mesencephalic
      aqueduct just before assessment of the feeding response to 4V or 3V galanin
      injection. Aqueduct occlusion did not alter the feeding induced by either 3V or
      4V galanin injection, indicating that galanin terminals in both the diencephalon
      and hindbrain are involved in control of food intake.

PMID- 9192402
TI  - Conflicts in the care of overweight patients: inconsistent rules and insufficient
      money.

PMID- 9192403
TI  - Growth of a molecular base for feeding: the mind body dualism.

PMID- 9192404
TI  - Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats. 1985.

PMID- 9192405
TI  - Cholecystokinin decreases food intake in rats. 1973.

PMID- 9192406
TI  - Eating or drinking elicited by direct adrenergic or cholinergic stimulation of
      hypothalamus. 1960.

PMID- 9192407
TI  - Superficial hemangiomas: associations and management.
AB  - The vast majority of hemangiomas, the most common skin tumor of infancy, are
      small lesions, easily recognized by their clinical features, and left to involute
      spontaneously. Hemangiomas also grow in a number of visceral locations, although
      rarely. In addition, associated malformations are reported. We analyzed 175 cases
      of severe superficial hemangiomas that represented approximately 10% of all
      hemangiomas evaluated from 1980 to 1995. In this particular group of severe
      hemangiomas, with marked female preponderance (6.6:1), symptomatic visceral
      hemangiomas were present in 20 of 175 patients (11.4%) and associated
      malformations were present in 12 patients (6.9%), with both present in 4
      patients. We describe these associations and discuss which hemangiomas required
      active treatment and which therapeutic modalities can be used. Progress has been
      made in the management of problem hemangiomas.

PMID- 9192409
TI  - Mal de Meleda: a report of four cases from the United Arab Emirates.
AB  - Mal de Meleda (MDM), or recessive transgressive palmoplantar keratoderma, is a
      rare disorder. MDM may have originated as a founder mutation that occurred on the
      island of Meleda, now Mljet, in Croatia, where it was first described. However,
      the condition has also been observed in countries distant from Mljet. The
      presentation of the disease in young patients has not been reported and the
      progressiveness of the lesions is debated. We examined four young United Arab
      Emirates nationals patients (ages 7 months to 12 years) who presented with
      keratoderma palmoplantaris (KPP) and transgressive pachyderma (TP) that had both
      been present before 1 year of age. KPP and TP were more pronounced in the two
      oldest patients. Family histories were consistent with autosomal recessive
      inheritance. The development of MDM lesions appears to be age-related. However,
      environment and individual factors may also play a role in the development and
      persistence of the lesions. Molecular genetic studies are necessary to establish
      whether the broad clinical presentation of the disease is due to allelic or
      genetic heterogeneities.

PMID- 9192408
TI  - Psychosocial stress and adaptive functioning in children and adolescents
      suffering from hypohidrotic ectodermal dysplasia.
AB  - In its fully manifest form, hypohidrotic ectodermal dysplasia (HED) leads to a
      typical dysmorphia of the face, referred to as "old man" facies. Few studies have
      been conducted on how children and adolescents deal with and adapt to the effects
      of this illness. The psychosocial stress and adaptive functioning of such
      patients was investigated by means of a semistructured interview conducted on a
      sample of 14 children and adolescents with varying degrees of this disease. The
      results revealed that adaptive functioning is not only dependent on the severity
      of symptoms. The child's intellectual potential and personality, how the disease
      is dealt with within the family, and reactions from the child's environment
      influence adaptive functioning in different ways.

PMID- 9192410
TI  - Microbiology of nonbullous impetigo.
AB  - Our objective was to establish the aerobic and anaerobic microbiology of
      nonbullous impetigo (NI) in children. We used a retrospective review of clinical
      microbiology laboratory and patients' records. Specimens were obtained from 40
      patients with NI lesions and showed bacterial growth. Aerobic or facultative
      anaerobic bacteria only were present in 24 patients (60%), strict anaerobic
      bacteria only in 5 patients (12.5%), and mixed anaerobic-aerobic flora was
      present in 11 patients (27.5%). Sixty-four isolates were recovered (1.6 per
      specimen): 43 aerobic or facultative, and 21 anaerobic. The predominant aerobic
      and facultative bacteria were Staphylococcus aureus (29 isolates), Group A beta
      hemolytic streptococcus (GABHS) (13 isolates), and Escherichia coli (1 isolate).
      The predominant anaerobes were Peptostreptococcus spp. (12), pigmented Prevotella
      spp. (5), Fusobacterium spp. (2), and Bacteroides fragilis (1). Single bacterial
      isolates were recovered in 17 patients (42.5%), 13 of which were S. aureus. S.
      aureus alone or mixed with GABHS or Peptostreptococcus spp. were isolated from
      all body sites. Mixed flora of Peptostreptococcus spp. with Prevotella spp. or
      Fusobacterium spp. was mostly found in infections of the head and neck, while E.
      coli mixed with B. fragilis and Peptostreptococcus spp. were isolated from one
      infection of the buttocks area. Thirty-three organisms isolated from 32 patients
      (80%) produced the enzyme beta-lactamase. This study demonstrates the
      polymicrobial aerobic-anaerobic microbiology of NI lesions.

PMID- 9192411
TI  - Hair whorl as an indicator of a mediastinal plexiform neurofibroma.
AB  - We report a boy with neurofibromatosis type 1 (NF-1) who had nonspecific
      respiratory symptoms and a mediastinal mass. In addition to multiple cate au lait
      macules and subcutaneous neurofibromas, he had a hair whorl over the spine at the
      level of a deep mediastinal mass demonstrated by CT scan and MR examination.
      Thoracoscopy and biopsy of the mass revealed a plexiform neurofibroma. The
      clinical sign of a hair whorl may assist the clinician in early recognition of a
      paraspinal plexiform neurofibroma.

PMID- 9192412
TI  - Cellular blue nevus of the scalp infiltrating the underlying bone: case report
      and review.
AB  - Cellular blue nevi (CBN) are benign tumors of the skin derived from dermal
      melanocytes histologically characterized by increased cellularity and often by a
      dual cell population of nevoid cells. CBN rarely tend to invade the underlying
      tissues. Only six cases of CBN of the scalp invading the skull have been
      reported. A new case of a CBN infiltrating the underlying bone is presented. The
      patient, a 23-year-old woman, had a large hairless area on her right parietal
      scalp, present since the early months of life. Her past medical history included,
      on the same site, the presence, at birth, of a raised, dark, soft and hairless
      mass that was subsequently electrodesiccated. Radiographs of the skull showed an
      area of osteolysis underlying the cutaneous lesion. Histologic examination of a
      biopsy specimen revealed a CBN of the scalp infiltrating the underlying bone.
      Surgical resection of the entire lesion was planned. There were no other
      anomalies or malignancies. The patient is currently being followed in our clinic.

PMID- 9192413
TI  - Granulomatous slack skin in childhood.
AB  - Granulomatous slack skin is an uncommon cutaneous T-helper cell lymphoma closely
      related to mycosis fungoides. To the best of our knowledge this disease has not
      been previously described in children. We report on an 11-year-old boy who
      presented with painless slack skin masses in the neck, right axilla and arm,
      anterior wall of the abdomen, both inguinal regions, and the malleolar and dorsal
      aspects of the feet. The disease started 3 years earlier with erythematous
      lesions on the neck and wrists. Histologic examination of a specimen from the
      abdominal mass revealed an extensive lymphoid infiltrate with scattered
      multinucleated giant cells extending from the papillary dermis to the subcutis.
      The lymphoid cells showed the following immunophenotype: CD43+ (MT1), CD45+,
      CD45RO+, CD20-. The phenotype of the giant cells was lysozyme positive, CD68+ and
      Mac387-. The tumoral lymphoid cells had clonal rearrangement for the gene of the
      beta chain of the T-cell receptor (C beta TCR). The disease could be controlled
      with systemic glucocorticoids. Due to the presence of many histiocytes arranged
      in aggregates in the papillary and mid-dermis, this case was initially considered
      to be a cutaneous form of histiocytosis. We recommend deep and extensive biopsies
      in patients with slack skin disease.

PMID- 9192415
TI  - Pyogenic granuloma with multiple dissemination in a burn lesion.
AB  - Pyogenic granuloma is a common vascular lesion in childhood. The occurrence of
      pyogenic granulomas after various kinds of trauma to the skin is quite common;
      however, multiple lesions secondary to a burn are very rare. For this reason, an
      18-month-old girl with multiple pyogenic granulomas following a second-degree
      burn is reported.

PMID- 9192414
TI  - Fish tank granuloma in a 14-month-old girl.
AB  - A 14-month-old girl developed a persistent ulcerated nodule on her right lower
      leg associated with further nodules along the thigh. A clinical diagnosis of fish
      tank granuloma was suspected because of tropical fish tanks at home. The
      diagnosis was confirmed when Mycobacterium marinum was isolated from low
      temperature culture of skin tissue. The child made a complete recovery following
      treatment with rifampicin for 6 months despite in vitro sensitivity tests
      reporting resistance. M. marinum infection is uncommon in children, but the
      diagnosis should be considered in children presenting with chronic skin lesions
      spreading in a sporotrichoid pattern.

PMID- 9192416
TI  - Lipodystrophia centrifugalis abdominalis infantilis: a case report.
AB  - We describe a typical case of lipodystrophia centrifugalis abdominalis
      infantilis. This rare disorder is almost exclusively seen in Japanese children.
      The patient, a 3-year-old girl of Chinese ancestry, had a depressed area of skin
      in the right groin which gradually spread across the abdomen. The lesion had a
      distinctive, slightly erythematous, raised border and regional lymphadenopathy
      was present.

PMID- 9192417
TI  - Demodicidosis in an immunodeficient child.
AB  - A 15-month-old girl developed acute lymphoblastic leukemia. Chemotherapy had
      induced a complete remission and she was continued on maintenance therapy. At 3
      years of age, she developed an eruption consisting of excoriated papules and
      pustules on the face. Demodex folliculorum seemed to be the cause. Topical
      treatment with metronidazole applied twice a day over a period of 2 weeks
      resulted in partial improvement. The dermatosis finally cleared gradually with
      oral erythromycin therapy and one overnight application of 1% lindane cream per
      week for 2 successive weeks.

PMID- 9192418
TI  - Neonatal lupus erythematosus related to maternal leukocytoclastic vasculitis.
AB  - Neonatal lupus erythematosus (NLE) is an autoimmune disease whose major findings
      are skin lesions and congenital heart block. Affected infants have maternal,
      transplacentally acquired, autoantibodies to Ro/SSA, La/SSB, or U1-RNP antigens.
      Anti-Ro/SSA is the predominant autoantibody, present in about 95% of cases.
      Mothers of babies with NLE may be asymptomatic initially or may have Sjogren
      syndrome, lupus erythematosus, overlap syndrome or, uncommonly, leukocytoclastic
      vasculitis. When evaluating a young woman with a cutaneous leucocytoclastic
      vasculitis, dermatologists should be aware of the possible presence of antibodies
      related to NLE. If any patient suffering a disorder related to NLE becomes
      pregnant, testing for autoantibodies and close obstetric prenatal care with fetal
      echocardiogram is necessary. In cases of fetal bradycardia, treatment with
      dexamethasone or betamethasone should be considered, as these drugs are
      accessible to the fetal circulation.

PMID- 9192419
TI  - Congenital syphilis associated with hyperlipoproteinemia.
AB  - An infant with congenital syphilis associated with transient disturbances of
      lipoprotein metabolism is reported. The dominant clinical sign was
      hepatosplenomegaly. Laboratory investigation upon admission revealed
      hyperimmunoglobulinemia and hyperchylomicronemia. After the administration of
      penicillin, the chylomicronemia ceased, but an increase of very low density
      lipoprotein fraction was observed. As the infant recovered, all the laboratory
      findings returned to normal. Hyperchylomicronemia was attributed to
      hyperimmunoglobulinemia. Absorption of immunoglobulins to lipoproteins can
      inhibit lipoprotein lipase activity. The increase in the very low density
      lipoprotein fraction was probably caused by the increase in serum lipoprotein
      production and the decrease in lipoprotein clearance that are frequently seen in
      patients with infectious diseases.

PMID- 9192420
TI  - Tinea capitis in a newborn caused by two organisms.
AB  - Tinea capitis is a common infection of childhood. There have been several reports
      of tinea capitis in newborns. Our patient presented at 19 days of age to the
      emergency room with a scalp lesion of 5 days duration. The fungal culture grew
      both Trichophyton rubrum and Trichophyton mentagrophytes. The patient was
      successfully treated with oral griseofulvin.

PMID- 9192421
TI  - Acute annular urticaria in infants and children.
AB  - Characteristic features of acute annular urticaria in 34 infants and small
      children were large, erythematous annular and polycyclic lesions with violaceous
      centers, eyelid, hand, and foot edema, absence of angioedema of the airway,
      absence of pruritus, spontaneous resolution in 8 to 10 days, and frequent history
      of furazolidone medication for diarrhea. Nondermatologists often misdiagnose
      acute annular urticaria as erythema multiforme and unnecessarily overtreat
      patients. The differential diagnosis with other conditions presenting with
      annular lesions in children is discussed.

PMID- 9192423
TI  - What syndrome is this? Ectrodactyly, ectodermal dysplasia, and cleft palate (EEC)
      syndrome.

PMID- 9192422
TI  - Treatment of childhood vulvar lichen sclerosus with potent topical
      corticosteroid.
AB  - Potent topical corticosteroid is recognized as the treatment of choice for vulvar
      lichen sclerosus in adults. A series of 11 children with vulvar lichen sclerosus
      were treated with the potent topical corticosteroid betamethasone dipropionate
      0.05%, seven using an optimized vehicle preparation. There was an excellent
      response to therapy in all cases. No serious adverse effects or unwanted sequelae
      occurred. Eight of the 11 children experienced complete remission after 3 months
      of therapy. In these children no maintenance therapy has been necessary during
      follow-up periods ranging from 3 to 18 months. Three children required
      maintenance therapy with a mild topical corticosteroid. We conclude that in
      children, as in adults, potent topical corticosteroid is a safe and effective
      treatment for vulvar lichen sclerosus.

PMID- 9192424
TI  - Congenital palmar nodule in an infant. Congenital fibrosarcoma.

PMID- 9192425
TI  - Localized elastosis perforans serpiginosa in a boy with Down syndrome.

PMID- 9192426
TI  - The successful treatment of oral candidiasis (thrush) in a pediatric patient
      using itraconazole.

PMID- 9192427
TI  - Pulse corticosteroid therapy in juvenile dermatomyositis.

PMID- 9192428
TI  - Linear and whorled nevoid hypermelanosis. A spectrum of pigmentary disorders.

PMID- 9192429
TI  - Gallbladder abnormalities associated with hypoplasia of the right lobe of the
      liver.
AB  - PURPOSE: We investigated the gallbladder abnormalities associated with anomalous
      right hepatic lobes using US, CT, and/or MRI. MATERIALS AND METHODS: The
      patients, four men and four women, ranged in age from 15 to 91 years, with a mean
      age of 59.5 years. The right lobe was hypoplastic in seven patients and was
      completely absent in one patient. RESULTS: The gallbladder was normally
      positioned in two patients (infrahepatic) and was absent in two patients. The
      gallbladder was located posterior to the liver in one patient (retrohepatic) and
      was located below the right hemidiaphragm in two patients (suprahepatic).
      Gallstones were present in one patient with jaundice and epigastralgia.
      CONCLUSION: Anomalous position or agenesis of the gallbladder often accompanies
      hypoplasia of the right hepatic lobe. Gallbladder position could be a good
      indicator of right hepatic lobe anomaly.

PMID- 9192430
TI  - Comparison of fast spin-echo and conventional spin-echo sequences in the MR
      diagnosis of rotator cuff tears.
AB  - The fast spin-echo (FSE) technique has been a successful alternative to
      conventional spin-echo (CSE) imaging in the brain, spine, and pelvis, but not in
      the knee. This study evaluated the performance of the FSE technique in comparison
      with the established CSE technique as a reference standard. Oblique coronal
      images of 30 shoulders were obtained by both FSE and CSE techniques. The FSE
      images were compared with CSE images in terms of blurring and motion artifact,
      fat signal intensity, structural conspicuity, and visualization of joint effusion
      and rotator cuff tears. We imaged 30 consecutive patients with suspected rotator
      cuff tears who were referred for MR examination. FSE images often were worse in
      blurring and motion artifact than CSE images. FSE images showed higher fat signal
      intensity, but visualized structural conspicuity, joint effusion, and rotator
      cuff tear as well as CSE images. Our results suggest that the FSE technique is
      not equal to the CSE technique but can be used for the diagnosis of rotator cuff
      tears.

PMID- 9192431
TI  - Value of low-dose gallium-67 imaging in detection of non-Hodgkin's lymphoma
      recurrence.
AB  - We evaluated the usefulness of low-dose Ga-67 scintigraphy as a diagnostic tool
      for the detection of non-Hodgkin's lymphoma recurrence. Forty-six patients were
      included in this retrospective study. Anterior and posterior whole body images
      were obtained two or three days after the injection of 74 MBq of Ga-67. Inter-
      and intraobserver variability in scintigraphic imaging interpretation was
      analyzed using the kappa (kappa) statistics. Ga-67 scintigraphy allowed correct
      detection of recurrence in 18 of 22 events (sensitivity, 82%), and excluded
      relapse in 34 of 39 events (specificity, 87%). The positive predictive value was
      0.78 and negative predictive value 0.89. All cases involving superficial lymph
      nodes (10/ 10) could be detected by Ga-67. Chest lesions were diagnosed with a
      sensitivity of 86% (6/7), bone and soft tissue 83% (5/6), and abdomen 80% (8/10).
      The sensitivity and specificity of CT were 91% (22/24) and 67% (8/12),
      respectively. In abdominal lesions, ultrasonography had sensitivity and
      specificity of 93% (14/15) and 94% (15/16), respectively. Kappa (kappa)
      statistics demonstrated good to strong inter- and intraobserver agreement in the
      interpretation of Ga-67 scintigraphy. The diagnostic results of low-dose Ga-67
      scans, currently applied in Japan, were similar to those reported by the authors
      using high doses of 296 MBq to 370 MBq. Ga-67 scintigraphy, even at low dose, is
      useful in the detection of non-Hodgkin's lymphoma recurrence.

PMID- 9192432
TI  - Assessment of breast cancer with dynamic gadolinium-enhanced MR imaging combined
      with magnetization transfer contrast using a newly developed breast surface coil
      for the supine position.
AB  - To assess the value of dynamic gadolinium-enhanced MR imaging combined with
      magnetization transfer contrast (MTC) of breast cancer by SPGR sequence, 15
      patients with breast cancer were imaged in the supine position with the newly
      developed breast coil in a 1.5 Tesla imager. Dynamic gadolinium-enhanced MR
      imaging combined with MTC (10 cases) and conventional dynamic gadolinium-enhanced
      MR imaging (5 cases) were performed after the administration of Gd-DTPA (0.2
      ml/kg). Sagittal images were obtained every 22 seconds during the first 264
      seconds. Thus, a total of 15 images were obtained in each lesion. The signal
      intensity ratio (SIR) of lesion to mammary glarid was calculated for each image
      as follows: (SI lesion/SI mammary gland)/(SI (pre)lesion/SI (pre)mammary gland).
      Dynamic gadolinium-enhanced MR imaging with MTC always allowed better SIR at 88
      seconds than conventional dynamic gadolinium-enhanced MR imaging after bolus
      injection (p < 0.01). Dynamic gadolinium-enhanced MR imaging with MTC improved
      detection of the boundary of the lesion and mammary gland.

PMID- 9192433
TI  - Lung cancer associated with punctate calcification: CT and histological
      correlation.
AB  - The etiology of punctate calcifications in lung cancer was evaluated on the basis
      of CT and histological correlations. Seven cases of lung cancer with punctate
      calcifications were demonstrated on CT. The patients had undergone surgical
      resection (five men and two women, 60-70 years old; six adenocarcinomas and one
      squamous cell carcinoma), and each case was evaluated for its CT appearance and
      histological findings. The number of calcifications observed on CT varied from
      one to six. Most were eccentric, but some calcifications in four cases were
      within the more central portion of the nodules. Overall, in six of seven cases
      the calcifications were histologically estimated to be due to preexisting old
      granulomatous fibrotic changes or fragments of bronchial cartilage incorporated
      within the growing tumors. In only one case were the calcifications psammoma
      bodies within the tumor. We conclude that punctate calcifications in lung cancers
      correspond mostly to preexisting calcified granuloma or degenerated bronchial
      cartilage.

PMID- 9192434
TI  - Long-term results of ethanol embolization of renal cell carcinoma.
AB  - This retrospective study was conducted to evaluate the long-term results of
      transarterial embolization with absolute ethanol (ethanol-TAE) for patients with
      renal cell carcinoma (RCC). Twenty-eight patients, including 15 stage IVb
      patients, underwent ethanol-TAE, with 12 of them followed by nephrectomy. The
      cumulative survival rates after 1, 3, and 5 years were 71%, 54%, and 54% in the
      surgical group, and 54%, 33%, and 22% in the non-surgical group. From the
      results, we recommend ethanol-TAE for advanced stage patients for the following
      reasons: first, it can be a useful alternative to nephrectomy in high-risk
      patients; second, ethanol-TAE can decrease the primary tumor size increasing
      operability; and third, local tumor control may result in longer survival.

PMID- 9192435
TI  - Glottic cancer with subglottic extension.
AB  - The outcomes of 27 patients with glottic cancer extending into the subglottis
      (GCSE) who were treated by surgery and radiation (n = 17) or radiation alone (n =
      10) during a 13-year period were retrospectively reviewed. Since this study was
      nonrandomized and retrospective, the patient groups were not equally matched with
      regard to age (p > 0.05), gender (p > 0.30), or disease stage (p > 0.05). The
      locoregional failure rate was 18 +/- [95% CI] 20% in patients who received
      combined therapy and 40 +/- 31% in persons treated by radiation alone (p = 0.20);
      the corresponding survival rates at two years were 53 +/- 24% and 42 +/- 31% (p >
      0.50). These findings suggest that GCSE may be better managed by a combination of
      surgery and radiotherapy than by the use of radiotherapy alone.

PMID- 9192436
TI  - Dedifferentiated chordoma arising in irradiated sacral chordoma.
AB  - A patient who received radiation therapy for a sacral lesion 10 years ago and
      eventually developed dedifferentiated chordoma at the primary site is reported.
      Initially, the patient received 54 Gy with Co-60 to the sacral tumor, and 6 years
      later an additional 50 Gy with 10 MV X-rays to the local recurrence. Four years
      later, an evident sacral tumor was noticed. When readmitted for re-confirmation
      of histology, a large rapidly growing lung metastasis was observed. The patient
      eventually died of progressive disease with incidental aspiration pneumonia. At
      autopsy, 10 years after the initial treatment, the recurrent sacral tumor proved
      to be dedifferentiated chordoma accompanied by typical chordoma. Although this
      case suggests the possible malignant transformation of chordoma rather than
      collision, the factors inducing this change remain unknown.

PMID- 9192437
TI  - Aggressive appearance of non-ossifying fibroma with pathologic fracture: a case
      report.
AB  - An 11-year-old boy presented with a lytic lesion in the proximal humeral
      metaphysis. In spite of an aggressively reactive appearance on plain radiography
      and MR imaging, this lesion proved to be a non-ossifying fibroma. Fracture of the
      cortical shell probably contributed to the relatively wide zone of transition and
      periosteal reaction on plain radiography and the reactive change on MR imaging.

PMID- 9192439
TI  - Synovial sarcoma in the prevertebral space of the neck: CT and MR findings.
AB  - Synovial sarcoma is a malignant soft tissue tumor arising in the vicinity of
      joints. However, synovial sarcoma can arise in the neck, and few imaging studies
      have demonstrated this situation. We report a case of synovial sarcoma in the
      prevertebral space of the neck, which was well demonstrated by MRI. Synovial
      sarcoma should be considered as a possibility in prevertebral pathological
      conditions.

PMID- 9192438
TI  - Pulmonary sclerosing hemangioma: report of a case with emphasis on dynamic MR
      imaging findings.
AB  - We report a case of pulmonary sclerosing hemangioma, a rare benign neoplasm.
      Marked homogeneous enhancement was noted on postcontrast CT. On the dynamic
      magnetic resonance (MR) imaging study, peak enhancement occurred 2 minutes after
      the administration of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).

PMID- 9192440
TI  - Intraosseous ganglion communicating with soft tissue counterpart.
AB  - We report the imaging and pathological findings of a rare case of intraosseous
      ganglion communicating with extraosseous counterpart. Both counterparts contain
      air and show rim-enhancement on T1-weighted images. Histopathologically, the
      enhanced-rim consists of reactive proliferation of capillary vessels due to
      degeneration.

PMID- 9192441
TI  - Hemodynamics in and around the ischemic focus: a local angiographic study via
      catheterization to the middle cerebral artery of the cat.
AB  - Local hemodynamics in and around the ischemic focus following middle cerebral
      artery occlusion (MCA) were investigated on angiography by direct infusion of
      contrast material into the MCA. In anesthetized cats, a catheter was introduced
      just distal to the site of MCA occlusion through the transorbital approach. MCA
      stump pressure following occlusion was approximately 20 mmHg. Solute infusion
      with hydrostatic pressure exceeding stump pressure by approximately 20 mmHg was
      found to be sufficient to perfuse the entire territory of the MCA. Serial
      angiography revealed that cortical MCA branches were fully opacified first, and
      within 10 seconds disappeared centrifugally from the penumbral area. When vessels
      were occluded together with the internal carotid artery and anterior cerebral
      artery, backflow was delayed such that the contrast material remained longer
      within the ischemic focus. This new technique provides a sound basis not only for
      investigating local hemodynamics but also for direct pharmacological manipulation
      of the ischemic vessels and brain tissues.

PMID- 9192442
TI  - Significance of informed consent and truth-telling for quality of life in
      terminal cancer patients.
AB  - For 12 patients with terminal stage cancer who died within the period from June
      1995 to the present, we retrospectively evaluated the correlation between the
      "information" concerning disclosure of the "diagnosis," "pathology," and
      "prognosis," with the length of the last admission before the death, "sedation"
      near death, and the choice of "do not resuscitate (DNR)." The average length of
      admission before death was markedly shorter for patients who had been told either
      the "diagnosis," "pathology," or "prognosis" than for patients who had not. A
      statistically significant difference was observed between those who had been told
      and those who had not been told the "pathology." Similarly, "sedation" tended to
      be done for those who had been provided with information on cancer. It was
      suggested that telling patients with terminal stage cancer the truth about
      "diagnosis," "pathology," and "prognosis" is important for them to spend a
      fulfilling terminal stage.

PMID- 9192443
TI  - Fully parametric and semi-parametric regression models for common events with
      covariate measurement error in main study/validation study designs.
AB  - The derivation of the likelihood function for binary data from two types of main
      study/validation study designs where model covariates are measured with error is
      elaborated. Rather than limiting consideration to a restricted family of models
      with convenient mathematical properties, we suggest that empirical
      considerations, customized to the data at hand, should drive model choices. The
      joint likelihood function for the main study, in which the covariates are
      measured with error, and the validation study, in which they are not, is
      maximized, and estimation and inference proceeds using standard theory. Although
      the choice of the measurement error model is driven by empirical considerations,
      the relatively small validation study sizes typically seen may lead to
      misspecification, resulting in bias in estimation and inference about exposure
      disease relationships. By using a nonparametric form for the measurement error
      model, the resulting semi-parametric methods suggested by Robins, Rotnitzky, and
      Zhao (1994, Journal of the American Statistical Association 89, 864-866) and
      Robins, Hsieh, and Newey (1995, Journal of the Royal Statistical Society, Series
      B 57, 409-424) are free from bias due to misspecification of the measurement
      error model, trading efficiency for robustness as usual. These fully and semi
      parametric methods are illustrated with a detailed example from a main
      study/validation study of the health effects of occupational exposure to
      chemotherapeutics among pharmacists (Valanis et al., 1993, American Journal of
      Hospital Pharmacy 50, 455-462). A constant, prevalence ratio model for common
      binary events, with gamma covariate measurement error, is derived and empirically
      verified by the available data. A careful reanalysis of the data, taking
      measurement error fully into account, leads to a threefold increase in the log
      relative risk and no loss of statistical power. The semi-parametric estimates are
      consistent with the parametric results, providing reassurance that important bias
      due to misspecification of the measurement error model is unlikely.

PMID- 9192444
TI  - Estimating medical costs from incomplete follow-up data.
AB  - Estimation of the average total cost for treating patients with a particular
      disease is often complicated by the fact that the survival times are censored on
      some study subjects and their subsequent costs are unknown. The naive sample
      average of the observed costs from all study subjects or from the uncensored
      cases only can be severely biased, and the standard survival analysis techniques
      are not applicable. To minimize the bias induced by censoring, we partition the
      entire time period of interest into a number of small intervals and estimate the
      average total cost either by the sum of the Kaplan-Meier estimator for the
      probability of dying in each interval multiplied by the sample mean of the total
      costs from the observed deaths in that interval or by the sum of the Kaplan-Meier
      estimator for the probability of being alive at the start of each interval
      multiplied by an appropriate estimator for the average cost over the interval
      conditional on surviving to the start of the interval. The resultant estimators
      are consistent if censoring occurs solely at the boundaries of the intervals. In
      addition, the estimators are asymptotically normal with easily estimated
      variances. Extensive numerical studies show that the asymptotic approximations
      are adequate for practical use and the biases of the proposed estimators are
      small even when censoring may occur in the interiors of the intervals. An ovarian
      cancer study is provided.

PMID- 9192445
TI  - Bayesian design and analysis of two x two factorial clinical trials.
AB  - The 2 x 2 factorial design has been advocated for improving the efficiency of
      clinical trials. Most such trials are designed on the assumption that there is no
      interaction between the levels of the factors and outcome. This assumption is
      often problematic, however, because interactions are usually possible in clinical
      trials and the sample sizes often used provide little power in testing for
      interactions. We consider the use of Bayesian methods for the design and analysis
      of 2 x 2 factorial clinical trials. This approach avoids the need to dichotomize
      one's assumptions that interactions either do or do not exist and provides a
      flexible approach to the design and analysis of such clinical trials. Exact
      results are developed for balanced factorial designs with normal response.
      Approximations are then presented for factorial designs based on the logistic
      model for binary response or the proportional hazards model for time-to-event
      data. The resulting approximate posterior distributions are normal and hence no
      extensive computations are required. Suggestions for specification of prior
      distributions are presented.

PMID- 9192446
TI  - Predictive variable selection for the multivariate linear model.
AB  - We develop a predictive Bayesian approach to variable selection in the
      multivariate linear model. A criterion derived from the Bayesian predictive
      density is proposed and a calibration is provided for it. Reference and
      informative priors are discussed, and an automated method that focuses on the
      response variable is proposed for specifying informative priors for the
      regression parameters. Relationships between the proposed criterion and other
      several well-known criteria are examined. Illustrative examples involving real
      data are given to demonstrate the methodology.

PMID- 9192447
TI  - Testing for treatment related trend with partially exchangeable clustered data.
AB  - When testing for treatment related effect, it is common to focus on data that
      describe some primary response, even though an experiment might yield data on
      secondary, less conspicuous effects. An example of such an experiment can be
      found in developmental toxicity studies, where a primary response might be the
      presence of skeletal malformation in a fetus, and a secondary effect might be
      reduced weight. In such studies, weight reduction may occur not only among
      malformed fetuses, but also among normal fetuses. In this paper, we use a
      likelihood ratio procedure to construct treatment related trend tests for
      developmental experiments with such outcomes. We assume that within each cluster,
      data are partially exchangeable and we use the presence or absence of
      malformations as categorical covariates. Two models are considered for the
      covariance structures: In the general model, partially exchangeable covariance
      matrices are used for each cluster within dose groups. In the homogeneous model,
      a common exchangeable covariance matrix is used for all clusters. Maximum
      likelihood estimates (MLEs) of unknown parameters in the general model are
      obtained by directly maximizing the log-likelihood function through careful
      numerical consideration, while MLEs of parameters of teh homogeneous model are
      obtained through an iterative procedure. Two applications to developmental
      toxicity data are described.

PMID- 9192448
TI  - Large sample tests for binary outcomes in fixed-dose combination drug studies.
AB  - Several test statistics are developed for testing the hypothesis that the
      combination of two drugs at a fixed-dose regimen is more effective than both of
      the single drugs used alone with respect to a dichotomous response variable. The
      response probability, logit, and arcsine-root scales are considered. The power
      function and the significance level are derived for large samples. For the sample
      size per group of 20 or greater, the power and type I error rate can be
      accurately calculated using the large sample power function when the response
      probability ranges from 0.2 to 0.8. These tests have similar power behaviors. In
      small samples, the large sample power functions of two of the tests can severely
      underestimate the type I error rate while overestimation can occur with one other
      test. The utilities of these tests are extended to unbalanced sample size cases.
      Generally speaking, there is a loss of power with unequal sample size allocation,
      but the loss is not severe.

PMID- 9192449
TI  - Analysis of aerial survey data on Florida manatee using Markov chain Monte Carlo.
AB  - We assess population trends of the Atlantic coast population of Florida manatee,
      Trichechus manatus latirostris, by reanalyzing aerial survey data collected
      between 1982 and 1992. To do so, we develop an explicit biological model that
      accounts for the method by which the manatees are counted, the mammals' movement
      between surveys, and the behavior of the population total over time. Bayesian
      inference, enabled by Markov chain Monte Carlo, is used to combine the survey
      data with the biological model. We compute marginal posterior distributions for
      all model parameters and predictive distributions for future counts. Several
      conclusions, such as a decreasing population growth rate and low sighting
      probabilities, are consistent across different prior specifications.

PMID- 9192450
TI  - A stochastic model for the analysis of bivariate longitudinal AIDS data.
AB  - We present a model for multivariate repeated measures that incorporates random
      effects, correlated stochastic processes, and measurement errors. The model is a
      multivariate generalization of the model for univariate longitudinal data given
      by Taylor, Cumberland, and Sy (1994, Journal of the American Statistical
      Association 89, 727-736). The stochastic process used in this paper is the
      multivariate integrated Ornstein-Uhlenbeck (OU) process, which includes Brownian
      motion and a random effects model as special limiting cases. This process is an
      underlying continuous-time autoregressive order [AR(1)] process for the
      derivatives of the multivariate observations. The model allows unequally spaced
      observations and missing values for some of the variables. We analyze CD4 T-cell
      and beta-2-microglobulin measurements of the seroconverters at multiple time
      points from the Los Angeles section of the Multicenter AIDS Cohort Study. The
      model allows us to investigate the relationship between CD4 and beta-2
      microglobulin through the correlations between their random effects and their
      serial correlation. The data suggest that CD4 and beta-2-microglobulin follow a
      bivariate Brownian motion process. The fit of the model implies that an increase
      in beta-2-microglobulin is associated with a decrease in future CD4 but not vice
      versa, agreeing with immunologic postulates about the relationship between these
      two variables.

PMID- 9192451
TI  - Signed rank statistics for coherent predictions.
AB  - A generalization of Wilcoxon's signed rank test is proposed for testing a dose
      response relationship with one or more outcomes. The test is useful in matched
      observational studies or in nonrandomized experiments that use dose-response
      relationships and predictions about multiple outcomes in an effort to distinguish
      actual treatment effects from hidden biases. A sensitivity analysis indicating
      whether a dose-response relationship or multiple predictions are confirmed with
      sufficient strength to reduce sensitivity to hidden bias is performed. Together,
      the test and the sensitivity analysis help to quantify the degree to which a
      coherent pattern of associations is present or absent, and the degree to which
      this strengthens or fails to strengthen evidence of cause and effect. Formal
      properties of tests of this kind are examined. The form of the optimal test is
      determined, though this test is not usable because it depends upon the values of
      the unknown parameters under study. Also examined are the conditions under which
      the proposed test resembles the optimal test, as well as the impact of various
      violations of those conditions on power. An example involving matched pairs
      exposed to varying doses of cadmium is considered in detail.

PMID- 9192452
TI  - Nonparametric analysis of clustered ROC curve data.
AB  - Current methods for estimating the accuracy of diagnostic tests require
      independence of the test results in the sample. However, cases in which there are
      multiple test results from the same patient are quite common. In such cases,
      estimation and inference of the accuracy of diagnostic tests must account for
      intracluster correlation. In the present paper, the structural components method
      of DeLong, DeLong, and Clarke-Pearson (1988, Biometrics 44, 837-844) is extended
      to the estimation of the Receiver Operating Characteristics (ROC) curve area for
      clustered data, incorporating the concepts of design effect and effective sample
      size used by Rao and Scott (1992, Biometrics 48, 577-585) for clustered binary
      data. Results of a Monte Carlo simulation study indicate that the size of
      statistical tests that assume independence is inflated in the presence of
      intracluster correlation. The proposed method, on the other hand, appropriately
      handles a wide variety of intracluster correlations, e.g., correlations between
      true disease statuses and between test results. In addition, the method can be
      applied to both continuous and ordinal test results. A strategy for estimating
      sample size requirements for future studies using clustered data is discussed.

PMID- 9192453
TI  - Nonparametric estimation of solid cancer size at metastasis and probability of
      presenting with metastasis at detection.
AB  - Two probabilistic characterizations of the relationship between the size of
      primary cancers and the occurrence of metastases are considered. The first is the
      distribution of tumor size at the point of metastatic transition, while the
      second is the probability that detectable metastases are present when cancer
      comes to medical attention. We show that the general model for this problem
      developed by Kimmel and Flehinger (1991, Biometrics 47, 987-1004) is
      unidentifiable. That is, the quantities to be estimated cannot be uniquely
      determined by the available information. An identifiable model that includes one
      limiting model of Kimmel and Flehinger (1991) as a special case is developed by
      using odds ratios. Under the new model, both quantities of interest are estimated
      by using a nonparametric maximum likelihood approach. The results are applied to
      two lung cancer data sets.

PMID- 9192454
TI  - Predictive model selection for repeated measures random effects models using
      Bayes factors.
AB  - The random effects model fit to repeated measures data is an extremely common
      model and data structure in current biostatistical practice. Modern data analysis
      often involves the selection of models within broad classes of prespecified
      models, but for models beyond the generalized linear model, few model-selection
      tools have been actively studied. In a Bayesian analysis, Bayes factors are the
      natural tool to use to explore these classes of models. In this paper, we develop
      a predictive approach for specifying the priors of a repeated measures random
      effects model with emphasis on selecting the fixed effects. The advantage of the
      predictive approach is that a single predictive specification is used to specify
      priors for all models considered. The methodology is applied to a pediatric pain
      data analysis.

PMID- 9192456
TI  - Effect of omitted confounders on the analysis of correlated binary data.
AB  - Marginal analysis using the generalized estimating equation approach is widely
      applied to correlated observations, as occur in studies with clusters and in
      longitudinal follow-up of individuals. In this article, we investigate the effect
      of confounding in such models. We assume that a risk factor x and a confounder z
      are related by a generalized linear model to the outcome y, which can be binary
      or ordinal. In order to investigate confounding arising from the omission of z, a
      joint structure for x and z must be specified. Modeling normally distributed
      (x,z) as sums of between- and within-individual (or cluster) components allows us
      to incorporate different degrees of between- and within-individual correlation.
      Such a structure includes, as special cases, cohort and period effects in
      longitudinal settings and random intercept models. The latter situation
      corresponds to allowing z to vary only on the between-individual (or cluster)
      level and to be uncorrelated with x, and leads to attenuation of the coefficient
      of x in marginal models with the logit and probit links. More complex situations
      occur when z is allowed to also vary on the within-individual (or cluster) level
      and when z is correlated with x. We examine the model specification and the
      expected bias when fitting a marginal model in the presence of the omitted
      confounder z. We derive general formulas and interpret the parameters and results
      in an ongoing cohort study. Testing for omitted covariates is also discussed.

PMID- 9192455
TI  - General formulas for obtaining the MLEs and the asymptotic variance-covariance
      matrix in mapping quantitative trait loci when using the EM algorithm.
AB  - We present in this paper general formulas for deriving the maximum likelihood
      estimates and the asymptotic variance-covariance matrix of the positions and
      effects of quantitative trait loci (QTLs) in a finite normal mixture model when
      the EM algorithm is used for mapping QTLs. The general formulas are based on two
      matrices D and Q, where D is the genetic design matrix, characterizing the
      genetic effects of the QTLs, and Q is the conditional probability matrix of QTL
      genotypes given flanking marker genotypes, containing the information on QTL
      positions. With the general formulas, it is relatively easy to extend QTL mapping
      analysis to using multiple marker intervals simultaneously for mapping multiple
      QTLs, for analyzing QTL epistasis, and for estimating the heritability of
      quantitative traits. Simulations were performed to evaluate the performance of
      the estimates of the asymptotic variances of QTL positions and effects.

PMID- 9192457
TI  - Estimation of excess risk from case-control data using Aalen's linear regression
      model.
AB  - We introduce methods for statistical inference in Aalen's non-parametric linear
      regression model of disease incidence (Aalen, 1989, Statistics in Medicine 8, 907
      925) from nested case-control data. These methods provide the basis for
      estimation of excess risk as a linear function of dose and absolute risk for a
      given exposure history. The methods are illustrated by estimating excess and
      absolute risks associated with radon exposure and smoking from nested case
      control samples from the Colorado Plateau uranium miners cohort.

PMID- 9192458
TI  - A latent process regression model for spatially correlated count data.
AB  - This paper proposes a regression model for spatially correlated count data that
      generalizes the work of Zeger (1988, Biometrika 75, 621-629) developed in a time
      series setting. In this approach, spatial correlation is introduced through a
      latent process, and the marginal mean function may contain spatial trends and
      covariates. Generalized estimating equations are used to estimate and perform
      marginal inference on the spatial trend and covariate effects. The feasibility of
      this approach is demonstrated using an example of the distribution of neuronal
      cell counts in a laboratory culture dish.

PMID- 9192459
TI  - Assessing interrater agreement from dependent data.
AB  - Estimation of interrater agreement for ordered categorical data is examined when
      the same sample is being assessed by various raters with different methods. We
      investigate the use of a latent model proposed by Qu, Piedmonte, and Medendorp
      (1995, Biomerics 51, 268-275) to estimate the correlation between raters for each
      method, and test for their equality. For each of the assessment methods, these
      correlations can be interpreted as the variance components of random effects
      representing subject and rater. This method is applied to an HIV study, in which
      the amount of ectopy on a woman's cervix is measured by both direct visual
      assessment and a computer planimetry method.

PMID- 9192460
TI  - Two-stage method of estimation for general linear growth curve models.
AB  - We extend the linear random-effects growth curve model (REGCM) (Laird and Ware,
      1982, Biometrics 38, 963-974) to study the effects of population covariates on
      one or more characteristics of the growth curve when the characteristics are
      expressed as linear combinations of the growth curve parameters. This definition
      includes the actual growth curve parameters (the usual model) or any subset of
      these parameters. Such an analysis would be cumbersome using standard growth
      curve methods because it would require reparameterization of the original growth
      curve. We implement a two-stage method of estimation based on the two-stage
      growth curve model used to describe the response. The resulting generalized least
      squares (GLS) estimator for the population parameters is consistent,
      asymptotically efficient, and multivariate normal when the number of individuals
      is large. It is also robust to model misspecification in terms of bias and
      efficiency of the parameter estimates compared to maximum likelihood with the
      usual REGCM. We apply the method to a study of factors affecting the growth rate
      of salmonellae in a cubic growth model, a characteristic that cannot be analyzed
      easily using standard techniques.

PMID- 9192461
TI  - Weighted logrank tests to detect a transient improvement in survivorship.
AB  - In investigating whether an intervention has an effect on survival, we exploit
      the flexibility of weighted logrank tests for constructing optimal tests
      sensitive to specified patterns of changes in the ratios or differences of the
      hazards as a function of time. The tests presented seem appropriate if either the
      intervention on trial imposes changes in life style, such as a diet modification
      or an exercise regimen, or if the effect of therapy itself is limited in
      duration, such as in the case of drugs for AIDS that may induce drug resistant
      viruses. For such problems, we postulate no difference between the hazards of the
      two groups initially, increased discrepancies as time goes on, and an eventual
      leveling-off of the discrepancies in hazards perhaps due to compliance problems
      or to adoption of the behavior change under study by individuals in the control
      group. We suggest a quadratic weight function for such problems and show how to
      evaluate the power of the proposed tests as well as their efficiency relative to
      other logrank tests. Other uses of quadratic weight functions, for example for
      evaluating effects with lag times, and for some parametric procedures are also
      described. Additive and multiplicative models are presented and both discrete and
      continuous times are considered.

PMID- 9192462
TI  - A random walk rule for phase I clinical trials.
AB  - We describe a family of random walk rules for the sequential allocation of dose
      levels to patients in a dose-response study, or phase I clinical trial. Patients
      are sequentially assigned the next higher, same, or next lower dose level
      according to some probability distribution, which may be determined by ethical
      considerations as well as the patient's response. It is shown that one can choose
      these probabilities in order to center dose level assignments unimodally around
      any target quantile of interest. Estimation of the quantile is discussed; the
      maximum likelihood estimator and its variance are derived under a two-parameter
      logistic distribution, and the maximum likelihood estimator is compared with
      other nonparametric estimators. Random walk rules have clear advantages: they are
      simple to implement, and finite and asymptotic distribution theory is completely
      worked out. For a specific random walk rule, we compute finite and asymptotic
      properties and give examples of its use in planning studies. Having the finite
      distribution theory available and tractable obviates the need for elaborate
      simulation studies to analyze the properties of the design. The small sample
      properties of our rule, as determined by exact theory, compare favorably to those
      of the continual reassessment method, determined by simulation.

PMID- 9192463
TI  - Estimation of absolute risk from nested case-control data.
AB  - Benichou and Gail (1995, Biometrics 51, 182-194) describe methods for estimating
      the absolute risk of developing disease given a set of covariate values over a
      specified time interval from a case-control study within a cohort. The methods
      are most suitable for unmatched case-control studies, and are restricted to
      categorical covariates. Expanding on methods for estimating relative mortality
      from nested case-control studies presented in Borgan and Langholz (1993,
      Biometrics 49, 593-602), we present methods for estimating absolute risk from
      individually matched nested case-control data. These methods accommodate
      continuous and time-dependent covariate histories, the sampling of cases, and
      various control sampling designs.

PMID- 9192465
TI  - Occurrence of non-ortho, mono-ortho and di-ortho substituted PCB congeners in
      polecats, stone martens and badgers from the state of Baden-Wurttemberg, Germany.
AB  - The concentrations of non-ortho, mono-ortho and di-ortho substituted PCB
      congeners in tissues of three European mustelid species--polecat, stone marten
      and badger--were determined. Median congener concentrations are comparable in the
      three species and are lower than in previous studies on polecats. In all samples
      PCB-126 contributes most to the TCDD-TEQ; it occurs in considerably higher
      concentrations in polecats. Additionally, amphibs, the main prey of polecats,
      were analysed. The total PCB intake of polecats feeding solely on amphibs would
      be below a critical level, considering the NOAEL for the reproduction of mink, a
      closely related species.

PMID- 9192464
TI  - Cytochrome P450 3A4 mediated metabolism of 2,4-dichlorophenol.
AB  - The metabolism of the environmental pollutant and hepatocarcinogen 2,4
      dichlorophenol (2,4-DCP) was studied using microsomal fractions and whole-cells
      of Saccharomyces cerevisiae containing human cytochrome P450 3A4. 2,4-DCP
      exhibited a typical type I substrate binding spectrum with a K, of 75 microM. 2,4
      DCP was metabolised into two major metabolites identified as 2-chloro-1,4
      hydroxyquinone and 2-chloro-1,4-benzoquinone in microsomal fractions and whole
      cells of yeast expressing human cytochrome P450 3A4. A further metabolite, 1,2,4
      hydroxybenzene, was also detected during biotransformation by whole cells, but
      was not observed in microsomal fractions. 2,4-DCP metabolism was dependent on
      NADPH in microsomal fractions and no activity was observed in microsomal
      fractions or whole cells of control transformants. Metabolites were identified by
      TLC followed by GC-MS.

PMID- 9192466
TI  - Species-specific selection on soil fungal population after olive mill waste-water
      treatment.
AB  - Soil was treated with olive mill waste water (OMW) in order to study the effect
      of this agriculture waste on soil fungal population. Changes in fungal
      composition were observed after soil pollution. In order to test OMW selective
      pressure, growth kinetics of Penicillium cyclopium, Scopulariopsis brevicaulis
      and Cladosporium cladosporioides were studied on solid media supplemented with
      different OMW concentrations. S. brevicaulis and C. cladosporioides did not grow
      at OMW concentration higher than 50%, while at concentrations lower than 50% a
      growth decrease was observed. Instead, P. cyclopium was able to actively grow at
      all concentrations of OMW tested. Therefore the OMW can influence and modify the
      soil fungal homeostasis.

PMID- 9192467
TI  - Biodegradation of [S,S], [R,R] and mixed stereoisomers of ethylene diamine
      disuccinic acid (EDDS), a transition metal chelator.
AB  - An in-depth biodegradation test program was executed on the hexadentate ligand
      Ethylene Diamine Di Succinate (EDDS). The EDDS structure contains two chiral
      carbon atoms, and has three stereoisomers ([R,R], [R,S]/[S,R], [S,S]). Our
      research has focused on the isomer mixture (i.e. 25%[S,S]; 25%[R,R];
      50%[S,R]/[R,S], as produced from the reaction of ethylene diamine with maleic
      anhydride) and on the single [S,S]- and [R,R]-isomers. Biodegradation screening
      of the 14C-labelled EDDS isomer mixture in a Batch Activated Sludge (BAS) test
      with various inocula revealed incomplete mineralization, up to ca. 65% after 28
      days. N-(2-aminoethyl) aspartic acid (AEAA), probably the d-isomer, was
      identified as the major portion of the 14C-material remaining in solution.
      Further testing revealed that the [S,S]-isomer is rapidly and completely
      mineralized in all test systems. By contrast, [R,R]-EDDS remained undegraded in a
      Sturm (OECD 301B) test, but was very slowly biotransformed into the recalcitrant
      metabolite AEAA in a BAS test. The [S,R]/[R,S] form undergoes biotransformation
      to AEAA in both high and low biomass systems. In a sewage treatment simulation
      test (OECD 303) the steady state DOC removal of mixture-EDDS in a CAS test was
      limited to 25-35%, even after extensive pre-acclimation, while the [S,S]-isomer
      achieved nearly complete removal (96%). This study illustrates the importance
      stereospecificity may have on the biodegradation and metabolite formation of a
      chemical. A biodegradation scheme for the different EDDS stereoisomers is
      proposed.

PMID- 9192468
TI  - Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in Baikal
      seal.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were
      determined in blubber tissue of one 3 month and two adult female seals from Lake
      Baikal. High PCDD and PCDF concentrations were found in the Baikal seal. The
      levels are comparable with those reported for ringed seals (phoca hispida) living
      in the Baltic sea, and Barrow Strait and Admiralty Inlet in the Canadian Arctic.

PMID- 9192469
TI  - Background contamination by coplanar polychlorinated biphenyls (PCBs) in trace
      level high resolution gas chromatography/high resolution mass spectrometry
      (HRGC/HRMS) analytical procedures.
AB  - The addition of the "dioxin-like" polychlorinated biphenyl (PCB) congeners to the
      assessment of risk associated with the 2,3,7,8-chlorine substituted dioxins and
      furans has dramatically increased the number of laboratories worldwide that are
      developing analytical procedures for their detection and quantitation. Most of
      these procedures are based on established sample preparation and analytical
      techniques employing high resolution gas chromatography/high resolution mass
      spectrometry (HRGC/HRMS), which are used for the analyses of dioxin/furans at low
      parts-per-trillion (ppt) levels. A significant and widespread problem that arises
      when using these sample preparation procedures for the analysis of coplanar PCBs
      is the presence of background levels of these congeners. Industrial processes,
      urban incineration, leaking electrical transformers, hazardous waste accidents,
      and improper waste disposal practices have released appreciable quantities of
      PCBs into the environment. This contamination has resulted in the global
      distribution of these compounds via the atmosphere and their ubiquitous presence
      in ambient air. The background presence of these compounds in method blanks must
      be addressed when determining the exact concentrations of these and other
      congeners in environmental samples. In this study reliable procedures were
      developed to accurately define these background levels and assess their
      variability over the course of the study. The background subtraction procedures
      developed and employed increase the probability that the values reported
      accurately represent the concentrations found in the samples and were not biased
      due to this background contamination.

PMID- 9192470
TI  - Response of higher plants to lead contaminated environment.
AB  - Lead concentration is increasing rapidly in the environment due to increased use
      of its sources by human society. Alarming concentrations of the metal have been
      reported in dust of densely populated urban areas and, water and land of various
      areas near the industrial waste disposals. Plants absorb lead and accumulation of
      the metal have been reported in roots, stems, leaves, root nodules and seeds etc.
      which increases with the increase in the exogenous lead level. Lead affects plant
      growth and productivity and the magnitude of the effects depend upon the plant
      species. Photosynthesis has been found to be one of the most sensitive plant
      processes and the effect of the metal is multifacial. Nitrate reduction is
      inhibited drastically in roots by the metal but in the leaves a differential
      effect is observed in various cultivars. Lead also inhibits nodulation, N
      fixation and ammonium assimilation in the root nodules. It appears that the toxic
      effect of the metal is primarily at physiological level and provision of certain
      inorganic salts can antagonize the toxic effects to some extent. Further
      responses of plants to the metal depend on various endogenous, environmental and
      nutritional factors. Some plants are able to tolerate excess of Pb+2 by involving
      processes like exclusion, compartmentalization or synthesizing metal detoxifying
      peptides-the phytochelatins.

PMID- 9192471
TI  - Biotechnological aspects of membrane function.
AB  - An overview is given of the biotechnological utilizability of various features of
      cell membranes. Techniques are given that describe how to make use of the barrier
      and transport functions of membranes for biotechnological purposes, ranging from
      cell permeabilization and construction of immobilized biocatalysts to
      manipulating excretion and uptake properties of the membranes by various methods.
      Glucose transporters, iron-transporting membrane systems, and pumps engaged in
      pleiotropic drug resistance are treated in more detail as particularly
      biotechnologically important membrane proteins.

PMID- 9192472
TI  - Effect of some environmental factors on the content and composition of microbial
      membrane lipids.
AB  - Lipids are known as a part of an effective adaptation mechanism reflecting the
      changes in the extracellular environment. The fluidity of biological membranes is
      influenced by the lipid structure and the portion of saturated, unsaturated,
      branched, or cyclic fatty acids in individual phospholipids. For all living
      organisms undergoing environmental adaptation, the fluidity can be changed only
      to a relatively small extent. This range is genetically determined and it is
      specific for every microorganism. This article presents recent knowledge about
      the influence of some environmental parameters (temperature, osmotic pressure,
      pH, the presence of salt or ethanol in medium) on a microbial membrane with the
      emphasis on regulation aspect in fatty acid biosynthesis. The main tools for
      regulation of membrane fluidity, for example, fatty acid desaturation or
      incorporation of branched and cyclic fatty acids into phospholipids, are
      discussed in more detail.

PMID- 9192473
TI  - Breaking the barrier: methods for reversible permeabilization of cellular
      membranes.
AB  - Plasma membrane constitutes a major barrier for the entry of hydrophilic
      molecules into the cell interior. Selective and reversible permeabilization of
      this barrier is a prerequisite for many biotechnological applications. This
      article reviews general principles of membrane permeabilization based on
      biological, chemical, and physical methods and mechanisms of the delivery of
      extrinsic substances to cell interior. The emphasis is given on the methods that
      have significantly contributed to our understanding of biological phenomena on
      membrane level or have been widely used in current biotechnology, such as
      delivery by membrane vehicles, electropermeabilization, microinjection, and
      biolistics. The mechanisms of the internalization of extrinsic substances and the
      advantages and drawbacks of individual techniques are discussed with respect to
      specific applications in biotechnology.

PMID- 9192474
TI  - Animal membrane receptors and adhesive molecules.
AB  - This review summarizes some important data, principles, opinions, commentaries,
      and modern methodology concerning the receptor structure, interactions, signaling
      and receptor-mediated cell functions. Three sections give a brief overview of the
      signaling synergy, multivariant signaling, and some reactions in phosphorylation
      networks. A concise report about the cytotoxic reaction of NK cells represents an
      example of multistage recognition reaction, involving differently acting
      receptors, changes in affinities of cell-cell interactions, and secretion of
      regulatory and cytotoxic molecules. Some interesting trends in receptor
      engineering, including antibody molecules as a special receptor phenomenon are
      mentioned in the final section.

PMID- 9192475
TI  - Targeting of drugs to cell surface receptors.
AB  - The new approach to the treatment of cancer or to immunomodulation is drug
      targeting. The effort to achieve either an absolute or a relative amplification
      of the tumoricidal effect of anticancer drugs through increased generation or
      acquisition of reactive molecules at the tumor site or a reduction of the toxic
      molecules available to the periphery has led to a number of strategies. Among
      them are (1) targeting using antibodies to their fragments, hormones,
      carbohydrates, and growth factors; (2) retargeting using bispecific antibodies;
      (3) construction of chimeric genes; (4) streptavidin-biotin based immunotherapy;
      (5) prodrug activation strategies (ADEPT); (6) antibody-targeted superantigens;
      and (7) gene delivery for the purpose of gene therapy.

PMID- 9192477
TI  - Mitral, tricuspid, and aortic valve repair or reconstruction.
AB  - The term repair is most properly applied to disease affecting the mitral and
      tricuspid valves or their annuli. The rationale, description, and analyses of the
      most recent evolution in these repair techniques are reviewed. The aortic valve
      cannot easily be repaired in the true sense of the word. The more proper term is
      sparing of the aortic valve in diseases that primarily affect the aortic root and
      annulus or reconstruction of the valve using pericardium in disease that
      primarily affects the valve. The evolution and current rationale for these
      techniques are also reviewed, and opinions regarding their future potential are
      rendered.

PMID- 9192476
TI  - Changing the transport of a cell.
AB  - The review deals with some of the transport functions of different systems that
      have been implicated with several pathological disorders. Membrane transport role
      in parasitic diseases and metal resistance is discussed as a few selected
      examples. Among various limitations that are encountered in recombinant
      technology and in heterologous expression of proteins, transport functions of the
      host organisms cannot be ignored. Recently, membrane transport has acquired a new
      emerging role in multidrug resistance. Several membrane transporters,
      particularly ATP binding cassette (ABC) proteins that are involved in drug
      resistance, have been identified throughout the evolutionary scale. The review
      briefly emphasizes that membranes are not only important as structural elements
      but are also adopted to perform diverse functions.

PMID- 9192478
TI  - Transesophageal echocardiography and the perioperative management of valvular
      heart disease.
AB  - Transesophageal echocardiography (TEE) is an integral part of decision-making and
      monitoring in the perioperative period for patients undergoing valvular heart
      surgery. Multiplanar probes with improved pre- and intraoperative evaluation, eg,
      improved accuracy of estimation of mitral regurgitation jet size, have led to a
      more precise surgical approach. In the intensive care unit, TEE is proving
      invaluable in diagnosing occult causes of clinical instability that are usually
      surgically correctable. Advances in imaging technology with three- and four
      dimensional TEE will facilitate preoperative decision-making, determine
      intraoperative approaches to valvular surgery, and provide earlier recognition of
      complications in the intensive care unit.

PMID- 9192480
TI  - Endocarditis.
AB  - Endocarditis remains a major worldwide problem despite significant advances in
      diagnostic and therapeutic interventions. This review centers on the recent
      studies that have been published in the past year concerning the epidemiologic,
      diagnostic, and therapeutic aspects of infective and noninfective endocarditis in
      both the general and special high-risk populations (eg, drug users, HIV-infected
      patients, and elderly patients).

PMID- 9192479
TI  - Allograft valves for aortic and mitral valve replacement.
AB  - Allograft valves have been used in cardiac valve replacement for 35 years. During
      much of this time, certain centers have used allograft aortic valves for aortic
      valve replacement and have reported excellent long-term results. After an initial
      period of failure using allograft mitral valves for mitral valve replacement, the
      technical problems of papillary muscle dehiscence and mitral regurgitation appear
      minimized by current investigators who now report encouraging early results. The
      current status of allograft use for aortic and mitral valve replacement is
      reviewed.

PMID- 9192481
TI  - The brouhaha surrounding cardiac transplantation: the need to place outcomes in
      perspective.

PMID- 9192482
TI  - Predicting outcome after cardiac transplantations: lessons from the Cardiac
      Transplant Research Database.
AB  - Survival and quality of life after transplantation are limited by posttransplant
      events such as rejection and infection. The description and subsequent prediction
      of these and other events is the goal of the Cardiac Transplant Research Database
      group. This paper provides a description of the purpose, methods of data
      collection and analysis, and results of the published data from the Cardiac
      Transplant Research Database. A review of the analyses of death, rejection, and
      infection is made along with a discussion of the clinical application of these
      data. Utilizing the data from the Cardiac Transplant Research Database, the
      clinician may apply established risk factors for posttransplant adverse events to
      individual patients.

PMID- 9192483
TI  - The challenge of endomyocardial biopsy interpretation in assessing cardiac
      allograft rejection.
AB  - The endomyocardial biopsy has long been the preferred technique for monitoring
      the rejection status of the cardiac allograft. During the past year, published
      reports have addressed important issues concerning the endomyocardial biopsy,
      including the reliability of the International Society for Heart and Lung
      Transplantation grading system; problem areas in posttransplantation biopsy
      interpretation, including grade 2 rejection and myocyte injury, Quilty lesions,
      and ischemic injury; the natural history of grade 2 rejection; the necessity of
      surveillance biopsies late in the posttransplantation course; and the efficacy of
      numerous noninvasive techniques in diagnosing or predicting rejection. No
      technique developed to date has been shown to have the sensitivity or specificity
      needed to replace the endomyocardial biopsy as a diagnostic tool. In addition,
      studies of endomyocardial biopsy specimens have furthered our understanding of
      the pathobiology of rejection and other transplant-related conditions.

PMID- 9192484
TI  - Pathophysiology and treatment of lipid perturbation after cardiac
      transplantation.
AB  - In this review we examine the complex interactions between lipoprotein
      metabolism, immunosuppressive drug therapy, and inflammation and the potential
      benefits of lipid-lowering drug therapy after heart transplantation. The newer
      formulations of cyclosporine, Neoral (Novartis Pharmaceuticals; Basle,
      Switzerland), and other newer agents such as tacrolimus may have advantages in
      regard to lipid metabolism as compared with traditional triple-drug
      immunosuppression. Lipoprotein levels may influence both the toxicity and
      efficacy of cyclosporine. Dyslipidemia may adversely influence inflammation and
      rejection in the allograft. Two recent clinical trials have shown that lipid
      lowering therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
      alone or in combination with low-density lipoprotein apheresis may confer
      significant benefits toward preventing transplant coronary artery disease.

PMID- 9192485
TI  - The use of tacrolimus and mycophenolate mofetil after cardiac transplantation.
AB  - Despite the advances in immunosuppressive therapy over the past 10 years, acute
      and recurrent cardiac allograft rejection remain significant problems. Although a
      number of immunosuppressive drugs and techniques are under development, few have
      progressed into clinical trials. Two novel agents, tacrolimus and mycophenolate
      mofetil, have recently undergone trials in liver, kidney and most recently,
      cardiac transplantation. Both agents are potent immunosuppressive agents, with
      quite different mechanisms of action and different side-effect profiles. Although
      the clinical trials information is currently limited, these drugs will likely
      play significant roles in the armamentarium of cardiac transplant
      immunosuppression.

PMID- 9192486
TI  - Radical alternatives to transplantation.
AB  - Because of the lack of donor hearts, thousands of patients annually die with end
      stage heart failure. Surgical alternatives to transplantation include partial
      left ventricular resection, dynamic cardiomyoplasty, and left ventricular assist
      devices. Partial left ventricular resection is an innovative procedure in which
      the heart is surgically reduced in size and cardiac function is dramatically
      improved immediately after surgery. Long-term follow-up is required to determine
      the success of this procedure. Dynamic cardiomyoplasty has been in use for 12
      years. In properly selected patients, it results in significant amelioration of
      symptoms and improvement in quality of life. Improved survival and objective
      physiologic improvement have not been documented. A randomized trial is now in
      progress to evaluate survival with surgical therapy versus survival with medical
      therapy. Left ventricular assist devices have been shown to be extremely
      effective as a short- and long-term "bridge" to heart transplantation in mortally
      ill patients. They are not approved for long-term support as an alternative to
      transplantation in the United States, but a randomized trial is now underway to
      compare the efficacy of these devices with the efficacy of medical therapy in New
      York Heart Association functional class IV patients.

PMID- 9192487
TI  - Cardiac xenotransplantation.
AB  - The severe shortage of human donor hearts has prompted several investigators to
      develop alternative strategies using cross-specie organs or xenografts. Unlike
      human allotransplantation, in which the important antigenic differences between
      donor and recipient are confined to the major histocompatibility and blood group
      antigens, xenotransplantation is confronted with the potential for multiple
      antigenic differences. In the pig-to-primate model of xenotransplantation, the
      primary obstacle to cross-species transplantation has been hyperacute rejection
      mediated by complement fixing antibodies directed against galactose alpha 1,3
      galactose (Gal alpha 1,3-Gal) epitopes on the pig endothelium. Conventional
      immunosuppression is unable to overcome hyperacute rejection; however, recent
      efforts in molecular biology have focused on genetically engineering porcine
      donors to express human proteins in their tissue. Transgenic pigs that express
      human complement regulatory proteins on their endothelium have been developed.
      Heterotopic transplantation of these transgenic donor hearts have had only
      moderate success. Alternative approaches attempt to eliminate the Gal alpha 1,3
      Gal epitopes by genetically "knocking out" the enzyme necessary for its
      synthesis, or to reduce the expression of Gal alpha 1,3-Gal epitopes by
      genetically inserting enzymes that redirect precursor molecules into alternative
      synthetic pathways. The technology to knock out the necessary enzymes in pigs is
      not yet available; however, pigs expressing the H-transferase gene have been
      developed and show reduced levels of Gal alpha 1,3-Gal epitopes. Although this
      "new breed" of transgenic pigs may overcome the barrier of hyperacute rejection,
      special strategies will need to be developed that target the next barrier of
      xenograft rejection.

PMID- 9192488
TI  - The new thinking on lipids and coronary artery disease.
AB  - Detection and treatment of high blood cholesterol has significantly reduced
      cardiovascular events. However, most individuals with coronary artery disease do
      not have hypercholesterolemia. Atherosclerosis is a complex interaction of
      inherited susceptibility and environmental issues that combine to create an
      atherogenic milieu. Appropriate diagnosis and treatment of patients with coronary
      artery disease can be of significant benefit, but if treatment is not
      individualized to the patient's individual metabolic abnormality, many patients
      will receive little to no benefit despite improved lipid profiles.

PMID- 9192489
TI  - The role of antioxidants in preventive cardiology.
AB  - Vitamin C, carotenoids, and vitamin E, the three main dietary sources of
      antioxidants, each effect lipid peroxidation and may reduce atherogenesis and
      lower the risk of coronary heart disease (CHD). Crosscultural studies of
      antioxidants find that regions with relatively low dietary intake tend to have
      higher rates of CHD, but in these studies it is difficult to account for other
      important cardiovascular risk factors. Evidence from observational studies with
      more detailed information do not support a cardiovascular benefit for vitamin C,
      although the cardiovascular effect of vitamin C supplementation among populations
      with marginal vitamin C deficiency is not known. Results from recent clinical
      trials of beta-carotene supplementation show no cardiovascular benefit, although
      several observational studies have found an inverse association between
      carotenoid intake or plasma levels and risk of CHD. The benefit reported in the
      observational studies may be due to consumption in foods rich in beta-carotene
      rather than the beta-carotene itself. The evidence for a cardiovascular benefit
      of antioxidants is strongest for vitamin E. Three large prospective studies find
      that vitamin E supplement users have approximately 40% lower rates of CHD. Short
      durations and doses of less than 100 IU/d (when data were available) have no
      significant effect. The effect of dietary vitamin E may be more modest but still
      associated with lower risk of CHD in populations in which vitamin E
      supplementation is infrequent. In a large randomized trial, a nonsignificant
      reduction in CHD risk was reported for 50 IU/d, although the dose may have been
      insufficient. A secondary prevention trial of 400 and 800 IU/day reported a
      strong reduction in nonfatal myocardial infarction, further supporting the large
      body of evidence that suggests that high doses of vitamin E reduce risk of CHD.

PMID- 9192490
TI  - Preventive cardiology in the elderly.
AB  - Cardiovascular disease is the leading cause of death world-wide in populations
      older than 65 years of age. The variation in cardiovascular mortality rates in
      this population indicates a substantial potential for effective coronary
      prevention. The highest risk for development of coronary heart disease is in
      individuals older than 65 years of age; many of the risk factors for coronary
      disease are modifiable, such that an older population may benefit substantially
      from a preventive program aimed at reducing coronary heart disease. The promotion
      of cardiovascular health at elderly age requires emphasis on the adoption of
      healthy lifestyles and the use of pharmacologic intervention when appropriate.

PMID- 9192491
TI  - Role of sodium reduction in the treatment and prevention of hypertension.
AB  - Evidence relating dietary sodium and blood pressure comes from a variety of
      sources: animal experiments, observational epidemiologic studies, migration
      studies, and randomized controlled trials. In this review, we examine new
      findings in each of these areas published during 1995 and 1996. Results from both
      observational epidemiologic studies and randomized controlled trials demonstrated
      a dose-response association between dietary sodium and blood pressure in humans.
      The relationship of dietary sodium to blood pressure was modified by age, race,
      body weight, and initial level of blood pressure. On average, a 100-mmol decrease
      in urinary sodium was associated with a reduction of approximately 3 mm Hg in
      systolic and a 2 mm Hg in diastolic blood pressure. In a general population, this
      blood pressure reduction would substantially reduce the societal burden of
      cardiovascular and renal diseases.

PMID- 9192492
TI  - Valvular heart disease.

PMID- 9192493
TI  - Heart transplantation.

PMID- 9192494
TI  - Prevention.

PMID- 9192495
TI  - D-glucose-sensitive neurosecretory cells of the crab Cancer borealis and negative
      feedback regulation of blood glucose level.
AB  - We studied the effects of glucose on cultured X-organ neurons of the crab Cancer
      borealis using single-electrode current- and voltage-clamp techniques. A
      subpopulation of the cells responded to D-glucose with a hyperpolarization. These
      cells, but not glucose-insensitive cells, showed immunoreactivity to crustacean
      hyperglycemic hormone (CHH), the hormone responsible for the elevation of blood
      glucose levels in crustaceans. Glucose-sensitive cells were also inhibited by
      serotonin and gamma-aminobutyric acid but were not affected by dopamine and Leu
      enkephalin. The response was specific for D-glucose, with an EC50 of 0.25 mmoll
      1. No response was seen to L-glucose, sucrose, galactose, mannose or fructose.
      The glucose response persisted in the absence of extracellular Na+ and in low
      Ca2+/Mn2+ saline. In voltage-clamp experiments, D-glucose evoked a small current
      with a reversal potential close to that of voltage-dependent K+ currents. We
      conclude that D-glucose activates a K+ current in CHH-immunoreactive cells that,
      in normal saline, induces a hyperpolarization. We propose that this enables
      glucose to regulate directly the release of CHH into the hemolymph, thus
      constituting a negative feedback mechanism regulating hemolymph glucose
      concentration.

PMID- 9192496
TI  - Modulation of ciliary beat frequency by neuropeptides from identified molluscan
      neurons.
AB  - Prior work in the nudibranch Tritonia diomedea indicated that certain
      identifiable pedal ganglion neurons (Pd5 and 6) innervating the foot synthesize
      three novel peptides (TPeps) that resemble Pedal peptide (Pep) identified in the
      sea hare Aplysia californica. We report here that when TPeps are applied directly
      to isolated ciliated patches of Tritonia diomedea foot epithelium, there is an
      increase in ciliary beating that normally drives locomotion. Exposure to TPeps
      also increases the ciliary beat frequency of cells isolated from the pedal
      epithelium, suggesting that the observed ciliomotor effects are direct and not
      mediated by intervening cells. Antibodies to TPep bind to specific cells of the
      brain and foot and to ciliated peripheral tissues in Tritonia diomedea and in the
      pulmonate gastropod Lymnaea stagnalis. We suggest, therefore, that TPeps may
      regulate the activity of ciliated cells responsible for pedal locomotion and
      other functions in gastropod molluscs.

PMID- 9192497
TI  - Rates of rewarming, heart and respiratory rates and their significance for oxygen
      transport during arousal from torpor in the smallest mammal, the Etruscan shrew
      Suncus etruscus.
AB  - We investigated the process of rewarming from torpor with respect to respiratory
      and circulatory oxygen transport properties in the smallest mammal, the Etruscan
      shrew Suncus etruscus. In seven adult Etruscan shrews with a mean body mass of
      2.4g, torpor was induced by deprivation of food and a cold environment. During
      arousal from torpor at an ambient temperature of 22 degrees C, the shrews
      actively rewarmed from the lowest mean (+/- S.D.) body temperature (Tb) of 12.1
      +/- 1.2 degrees C to 20 degrees C at a rate of 0.43 +/- 0.14 degree C min-1, from
      20 to 24 degrees C at a rate of 0.8 degree C min-1, and from 24 to 36 degrees C
      at a rate of 1.1 +/- 0.1 degrees C min-1. The mean rate from 12 degrees C to
      normothermia amounted to 0.83 degree C min-1, which is among the highest values
      recorded in mammals. During rewarming, the heart rate increased exponentially
      (Q10 = 2.2) from 100 to 800-1200 min-1, whereas the respiratory rate increased
      linearly from 50 to 600-800 min-1. These rates are higher than the heart and
      respiratory rates reported for other small mammals at the same Tb. The fraction
      of brown adipose tissue (BAT) was 9.2 +/- 1.6% of body mass, which is higher than
      in any other mammal. Up to a body temperature of approximately 17 degrees C, the
      heat for rewarming was mainly produced in the BAT; above this value, considerable
      activity of the skeletal muscles enhanced thermogenesis. Estimation of the mixed
      venous oxygen partial pressure showed that, at the tissue level, the rewarming
      process corresponds to heavy work conditions. The ventilatory system is adapted
      such that during rewarming, in addition to the appropriate oxygen transport
      capacity, there is also a capacity for hyperventilation.

PMID- 9192499
TI  - Reporter gene constructs suggest that the Caenorhabditis elegans avermectin
      receptor beta-subunit is expressed solely in the pharynx.
AB  - Gene promoter/LacZ reporter constructs were made in order to analyse the
      expression of the beta-subunit of the Caenorhabditis elegans glutamate-gated Cl-
      channel (Glu-Cl) receptor. Southern blot analysis of the C. elegans cosmid C35E8
      identified a 4kbp EcoRI fragment which contained the 5' portion of the Glu-Cl
      beta coding sequence together with 5' flanking sequences. This was subcloned and
      used as the template for polymerase chain reaction (PCR) amplification of a DNA
      fragment encoding the first 24 amino acid residues of Glu-Cl beta together with
      1.4 kbp of 5' genomic sequence. The fragment was subcloned into the LacZ
      expression vector pPD22.11 to form a translational reporter fusion. After
      injection of the construct into worms, six stably transformed lines were
      established and assayed for beta-galactosidase activity. Stained nuclei were
      observed in the pharyngeal metacorpus in adults and in all larval stages, and
      stained nuclei were seen in many embryos undergoing morphogenesis. Additional
      stained nuclei towards the terminal bulb of the pharynx were observed in larval
      stages. These results provide further evidence that the Glu-Cl receptor mediates
      the glutamatergic inhibition of pharyngeal muscle via the M3 motor neurone and
      point to inhibition of pharyngeal pumping as a major mode of action for
      avermectins.

PMID- 9192498
TI  - Molecular analysis of FMRFamide- and FMRFamide-related peptides (FaRPS) in the
      cuttlefish Sepia officinalis.
AB  - The display of complex color patterns of the cuttlefish Sepia officinalis is
      under the regulation of the FMRFamide-related peptide (FaRP) family, but their
      exact identities are unknown. We report the isolation and characterization of a
      full-length FaRP cDNA from the brain of S. officinalis. This cDNA is 1850 base
      pairs long, including an open reading frame of 996 base pairs. The cDNA encodes a
      precursor protein containing four FaRPs: ALSGDAFLRF, FIRF, FLRF and FMRF. Each
      propeptide has a C-terminal glycine residue that is presumably converted post
      translationally to an amide. Every FaRP propeptide is also flanked by basic amino
      acid residues at the amino and carboxy termini, indicative of putative cleavage
      sites during post-translational processing. Each of the four FaRPs encoded by
      this cDNA causes chromatophore expansion when assayed in an in vitro
      chromatophore bioassay. Thus, it is likely that one or more of the FaRPs
      identified in this study are involved in controlling chromatophore activity in
      cuttlefish.

PMID- 9192500
TI  - Hummingbird hovering energetics during moult of primary flight feathers.
AB  - How does a hovering hummingbird compensate for the loss of flight feathers during
      moult when the mechanism of lift force generation by flapping wings is impaired?
      The flight performance of five individual ruby-throated hummingbirds with
      moulting primary flight feathers and reduced wing area was compared with that
      before their moult. Hummingbirds were flown in reduced air densities using
      normoxic heliox so that a range of flight energetics was displayed. The rate of
      moulting and the extent of wing area loss varied among individuals. One female
      could tolerate a 30% loss of wing area in moulting and flew with only three outer
      primaries per wing. Further exploratory study using the artificial reduction of
      wing area, either by cutting the tips of the outer primaries of a male or by
      plucking the secondaries of two females, suggested that secondaries play a minor
      role in lift force generation during hovering whereas the tip area of primaries
      is crucial. For the five birds, ranges of whole-bird oxygen consumption rates,
      wingbeat kinematics (stroke amplitude) and lift coefficients did not vary during
      the moult. This constancy was mainly achieved through weight loss that alleviated
      aerodynamic force requirements for weight support during hovering. Since the
      metabolic power expenditure during moult was similar to that of normal birds but
      the mechanical power requirement was reduced, the flight efficiency also showed a
      sharp reduction during moult. This increased cost of flight may result from
      disruption of the integrity of the flight machinery. Overall, the control of body
      mass in hummingbirds can provide similar aerodynamic, muscle mechanical and
      physiological capacities under conditions of variable flight demand.

PMID- 9192501
TI  - [The National Society Mitt Livstestament (My Living Will)--promotes active
      euthanasia].

PMID- 9192502
TI  - Androgen-receptor blockade does not impair bone mineral density in adolescent
      females.
AB  - The effect of peripheral androgen hypersensitivity on bone mineral density (BMD)
      was investigated in a group of adolescent women with idiopathic hirsutism (n =
      17; mean age 17.0 +/- 1.7 years). The effect of long-term androgen-receptor
      blockade with flutamide (500 mg daily in two divided doses for 12 months) on BMD
      was assessed too. BMD was measured at lumbar spine (L2-L4) by a dual energy X-ray
      densitometer. Before flutamide treatment, patient BMD (1.14 +/- 0.07 g/cm2) was
      not significantly different from that of the control group (1.16 +/- 0.12 g/cm2,
      n = 22), and was normal for age and sex (BMD 0.14 +/- 0.69 SDS, P = NS vs. 0).
      After 12 months of treatment, absolute BMD in patients increased (1.18 +/- 0.08
      g/cm2, P < 0.002), but SDS BMD did not change (0.21 +/- 0.72, P = NS vs.
      baseline). Flutamide treatment determined a clinical, marked improvement of
      androgen hypersensitivity (Ferriman-Gallwey score: before 22.0 +/- 6.2; 6 months:
      13.2 +/- 6.4, P < 0.003; 12 months; 7.6 +/- 4.1, P < 0. 001; acne score: before
      3.8 +/- 0.8; 3 months 0.8 +/- 0.5, P < 0. 001; later disappeared). The serum
      levels of 3alpha-androstenediol-glucoronide decreased (before: 8.6 +/- 1.1
      microg/liter; 12 months: 7.2 +/- 1.0 microg/liter, P < 0.02), whereas the other
      endocrinological parameters did not change. No relationship was found between BMD
      and clinical or biochemical parameters of hyperandrogenism. We concluded that in
      adolescent women, peripheral hyperandrogenism is not associated with abnormal
      BMD; long-term treatment with flutamide, which blocks the androgen receptor, does
      not alter their BMD.

PMID- 9192503
TI  - The response to calcitriol therapy in postmenopausal osteoporotic women is a
      function of initial calcium absorptive status.
AB  - Calcitriol is used in the treatment of osteoporosis but the indications for its
      use have not been clearly defined. Because it stimulates calcium absorption, we
      have tended to select osteoporotic patients with low calcium absorption for this
      therapy and now report the results. We measured the hourly fractional rate of
      calcium absorption (alpha) with 45Ca and fasting urinary calcium/creatinine
      (Ca/Cr) and hydroxyproline/creatinine (OHPr/Cr) in 103 postmenopausal women aged
      68 (0.67SE) years with vertebral compression fractures (77) or forearm or
      vertebral bone density below the young normal range (26). They were given 0.25
      microg daily of calcitriol (Rocaltrol, Roche, Basle, Switzerland) with a 1 g
      calcium supplement daily for 6-12 weeks, when the biochemical tests were
      repeated. Initial OHPr/Cr was inversely related to initial alpha (P = 0.001) and
      positively to initial Ca/Cr (P < 0.001). alpha rose on therapy from 0.47 (0.018)
      to 0.59 (0.018) per hour (P < 0. 001) and OHPr/Cr fell in the whole group from
      19.1 (0.83) to 13.8 (0. 58) (P < 0.001). The change in alpha on therapy
      (corrected for the "regression to the mean effect") was inversely related to
      initial alpha (P < 0.001) as was the change in OHPr/Cr (P = 0.001). There was no
      relationship, however, between initial Ca/Cr and either the rise in alpha or the
      fall in OHPr/Cr on therapy. The data support the concept that low calcium
      absorption is a cause of negative calcium balance in postmenopausal osteoporosis
      and that the effectiveness of calcitriol therapy is inversely related to the
      initial rate of calcium absorption.

PMID- 9192504
TI  - Equivalence of nasal spray and subcutaneous formulations of salmon calcitonin.
AB  - The aim of this study was to assess the efficacy and safety of nasal spray and
      subcutaneous formulations of salmon calcitonin. Two-hundred-four patients, 27
      males and 177 females, aged 72 years on average, with a recent, painful,
      vertebral crush fracture were given either 50 IU/day of subcutaneous salmon
      calcitonin (SCSCT, 102 patients) or 200 IU/day of intranasal salmon calcitonin
      (INSCT, 102 patients) for 30 consecutive days, according to a double-blind,
      double-placebo design. The two-sided 95% confidence interval of the difference
      between the two formulations for the pain on D30 assessed by Huskisson's Visual
      Analogue Scale (VAS) [-5.3 mm, 7.9 mm] was included in the [-10 mm, 10 mm]
      reference interval. Equivalence of the two formulations, was demonstrated. At the
      end of the study, the 95% confidence intervals of VAS of both treatment groups
      were included in the [0 mm, 30 mm] interval, which is considered to be clinically
      pertinent. Relief was obtained in less than 10 days for more than 50% of
      patients. The urinary hydroxyproline/creatinine and calcium/creatinine ratios
      remained constant between D1 and D30 with both formulations. General safety was
      comparable between the two formulations. Local safety of INSCT was similar to
      that of its placebo.

PMID- 9192505
TI  - Cytokines expressed in multinucleated cells: Paget's disease and giant cell
      tumors versus normal bone.
AB  - Human osteoclasts are well characterized multinucleated cells whose function is
      the directed resorption of normal bone (NB). Osteoclastic bone destruction
      accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of
      bone and giant cell tumors of bone (GCTB). The mechanism of this stimulation of
      osteoclastic bone resorption is unknown. This study was designed to detect
      cytokines present in the multinucleated cells of PD and GCTB in order to
      determine whether cytokine abnormalities exist to account for bone lysis. Nine
      cytokines, representing the functions of bone resorption, angiogenesis, tumor
      necrosis, bone cell proliferation, and osteoblast-osteoclast coupling, were
      examined by immunohistochemistry using tissue samples from 15 NB, 17 PD, and 19
      GCTB patients. Standard nonparametric statistical analysis showed a significant
      increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB
      for interleukin-6 (Il-6), tumor necrosis factor beta (TNFbeta), epidermal growth
      factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth
      factor (bFGF). There was a statistically significant decrease in immunostaining
      of giant cells of GCTB as compared with NB for transforming growth factor beta
      (TGFbeta), but no other differences from normal osteoclasts. The increase in
      staining of PD osteoclasts over the giant cells of GCTB was significant (P <
      0.01) for Il-6, TNFbeta, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P <
      0. 05) for Il-1 and EGF. It was concluded that marked cytokine differences exist
      in vivo between osteoclasts of NB and PD lesions consistent with stimulated
      resorption. Alternatively, "osteoclastoma" cells in the center of the tumor did
      not overexpress the cytokines associated with bone lysis, suggesting some other
      mechanism for stimulated resorption.

PMID- 9192506
TI  - Increased bone mineral density after prolonged electrically induced cycle
      training of paralyzed limbs in spinal cord injured man.
AB  - Spinal cord injured (SCI) individuals have a substantial loss of bone mass in the
      lower limbs, equaling approximately 50% of normal values in the proximal tibia,
      and this has been associated with a high incidence of low impact fractures. To
      evaluate if this inactivity-associated condition in the SCI population can be
      reversed with prolonged physical training, ten SCI individuals [ages 35.3 +/- 2.3
      years (mean +/- standard error [SE]); post injury time: 12.5 +/- 2.7 years, range
      2-24 years; level of lesion: C6-Th4; weight: 78 +/- 3.8 kg] performed 12 months
      of Functional Electrical Stimulated (FES) upright cycling for 30 min per day, 3
      days per week, followed by six months with only one weekly training session. Bone
      mineral density (BMD) was determined before training and 12 and 18 months later.
      BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by
      dual energy absorptiometry (DEXA, Nordland XR 26 MK1). Before training, BMD was
      in the proximal tibia (52%), as well as in the femoral neck, lower in SCI
      subjects than in controls of same age (P < 0.05). BMD of the lumbar spine did not
      differ between groups (P > 0.05). After 12 months of training, the BMD of the
      proximal tibia had increased 10%, from 0.49 +/- 0.04 to 0. 54 +/- 0.04 g/cm2 (P <
      0.05). After a further 6 months with reduced training, the BMD in the proximal
      tibia no longer differed from the BMD before training (P > 0.05). No changes were
      observed in the lumbar spine or in the femoral neck in response to FES cycle
      training. It is concluded that in SCI, the loss of bone mass in the proximal
      tibia can be partially reversed by regular long-term FES cycle exercise. However,
      one exercise session per week is insufficient to maintain this increase.

PMID- 9192507
TI  - Water bath and contact methods in ultrasonic evaluation of bone.
AB  - Ultrasonic devices for the measurement of speed of sound (SOS) and broadband
      ultrasonic attenuation (BUA) generally use either a contact or water bath method.
      The aim of this study was to compare these two methods while determining the
      influence of soft tissue, pathlength (heel width and bone width), and a fixed
      heel dimension on SOS (m/second) and BUA (dB/MHz). Ultrasonic measurements were
      made using a CUBA Research system utilizing a pair of 1 MHz unfocused transducers
      with mean precision CV = 0.7% and 6.0% for all SOS and BUA measurements,
      respectively. SOS and BUA were determined in 24 human cadaveric heels under three
      conditions: contact method (heel intact), water bath method (heel intact), water
      bath method (no soft tissue). Although there were significant differences between
      measurements using contact and water bath techniques (heel intact), their
      correlations were high (r = 0.858 for SOS and r = 0. 937 for BUA; P < 0.001).
      After removal of soft tissue, SOS significantly increased (78 m/second; P <
      0.001) whereas there was no change in BUA (P > 0.05). Heel width correlated with
      SOS measurements (-0.224 < r < -0.347; P < 0.001) and bone width correlated with
      BUA measurements (0.198 < r < 0.276; P < 0.001). The practice of using a fixed
      heel dimension (Lunar Achilles) was investigated by comparing SOS calculated with
      measured heel thickness and a value of 4 cm (Lunar Achilles). SOS increased by 42
      m/second (2.7%) using the fixed heel dimension compared with measured heel
      widths. This study demonstrates the similarity between contact and water bath
      based methods, while showing that the presence of soft tissue reduces SOS but has
      no effect on BUA. The use of a fixed heel dimension for calculation of SOS
      overestimates values obtained when using measured heel dimensions, though the
      values correlate highly (r = 0.98, P < 0.001). In addition, an increase in heel
      width tends to cause an underestimation of SOS whereas an increase in bone width
      tends to overestimate BUA, although the effects are relatively small.

PMID- 9192508
TI  - Bone mineral density in patients with human immunodeficiency virus infection.
AB  - The Object of this study was to determine whether HIV infection is associated
      with decreased bone mineral density (BMD). BMD was measured by dual-energy X-ray
      absorptiometry at total body, lumbar spine, and hip in 45 men with HIV infection
      and compared with sex, age, and weight-matched controls. Repeat scans were
      performed after a mean interval of 15 months in 21 patients to determine whether
      there were detectable losses of BMD. Compared with controls, the HIV patients had
      marginally lower BMD at the lumbar spine (P = 0.04) but there was no significant
      difference in total body or hip BMD. None of the patients had reduced BMD to
      levels associated with a diagnosis of osteoporosis. On longitudinal follow-up, a
      small decrease in total body BMD (-1.6%; P = 0.02) was observed but there was no
      significant change in spine and hip BMD. In spite of the many features of HIV
      infection that might be expected to cause a reduction in BMD such as cytokine
      activation, decreased physical activity, small bowel disease, hypogonadism, and
      direct infection of osteogenic cells by HIV, we found only minimal differences in
      BMD between HIV patients and controls. Furthermore, the HIV patients studied did
      not appear to show excessive loss in bone mineral over time.

PMID- 9192509
TI  - Growth hormone, osteoblasts, and marrow adipocytes: a case report.
AB  - Though growth hormone stimulates markers of bone formation in adults, its in vivo
      effect on osteoblasts is unknown. We have used histomorphometry of fluorochrome
      labeled iliac crest biopsies along with biochemical markers to assess bone
      formation and resorption rates before and after treatment with growth hormone
      (Genotropin; 3. 0 IU/day for 6 months) in combination with calcitonin (Miacalcin
      nasal: 200 IU daily) in a man with osteonecrosis and decreased spinal bone
      mineral density (BMD). Treatment resulted in increases in indices of bone
      formation and a marked increase in osteoblast number and osteoid surface, with a
      concomitant decrease in the number and size of marrow adipocytes. There was no
      change in spinal or total BMD. These data confirm the stimulatory effect of
      growth hormone on the osteoblast population and suggest that this may occur by
      the commitment of early precursor cells to the osteoblastic as opposed to the
      adipocytic lineage.

PMID- 9192510
TI  - Familial hypocalciuric hypercalcemia in Israel: a preliminary report.
AB  - Familial hypocalciuric hypercalcemia (FHH) is often considered in the
      differential diagnosis of hyperparathyroidism, but is rarely diagnosed. So far,
      FHH has not been documented in Israel. This report presents preliminary evidence
      for the occurrence of FHH in Israel.

PMID- 9192511
TI  - Comparison of calcitriol treatment with etidronate-calcitriol and calcitonin
      calcitriol combinations in Turkish women with postmenopausal osteoporosis: a
      prospective study.
AB  - Calcitriol has been widely used in the management of osteoporosis, but its
      efficiency is a matter of controversy. It is not known whether combinations of
      calcitriol and antiresorptive agents such as etidronate and calcitonin are
      superior to calcitriol alone in the treatment of postmenopausal osteoporosis. To
      make this determination, 30 Turkish women with postmenopausal osteoporosis
      between 45 and 68 years of age were randomized to receive either intermittent
      cyclical etidronate (400 mg/day, for 14 days) followed by 60 days of cyclical
      calcitriol therapy 0.25 microg twice daily (group 1; n = 10), or calcitriol 0.25
      microg twice daily (group 2; n = 10), or calcitriol 0.25 microg/day in
      combination with 100 IU intranasal salmon calcitonin taken every other day (group
      3; n = 10) through a 1-year period. Bone mineral density (BMD) of lumbar spine
      (L2 to L4) was determined for each patient by dual-photon absorptiometry (153Gd)
      at baseline, after 6 months, and at the end of the study. There was no
      significant difference among groups with respect to mean spinal BMD at baseline,
      after 6, and after 12 months. No significant spinal BMD changes occurred in any
      group from baseline, after 6 months, and after 12 months. Four patients in groups
      1 and 2 and five patients in group 3 developed hypercalcemia at least once during
      therapy. Hypercalciuria occurred at least once in 9, 10, and 7 patients in groups
      1, 2, and 3, respectively. One patient in group 2 developed a renal stone at the
      end of the study. Mean urine hydroxyproline levels did not change significantly
      in any group with respect to baseline. The data suggest that one-year treatment
      with calcitriol, given either alone or in combination with antiresorptive agents,
      does not improve spinal BMD in Turkish women with postmenopausal osteoporosis,
      and is associated with a high rate of adverse events.

PMID- 9192512
TI  - Total body bone measurements in spinal osteoporosis by dual-energy X-ray
      absorptiometry.
AB  - Changes in total body bone mineral content (BMCTB) and density (BMDTB), and the T
      score of BMCTB and (BMDTB) were evaluated in relation to the number of vertebral
      fractures in women with postmenopausal osteoporosis for the purpose of defining
      deviations in these parameters that could be predictive of the occurrence of
      vertebral fracture. The study group consisted of 62 women diagnosed with
      postmenopausal osteoporosis. All of them had two or more spinal fractures.
      Regression analysis of the number of fractures against each parameter studied
      indicated that the following were predictive of the risk of fracture: a reduction
      of -0.5 in the T-score of both BMCTB and BMDTB (P < 0.0001) and a loss of about
      135 g of BMCTB or 0. 058 g/cm2 of BMDTB (P < 0.0001). The fact that such changes
      were found during the follow-up of women with osteoporosis highlights the
      importance of bone mass measurements during follow-up.

PMID- 9192513
TI  - Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on
      four cases in one family.
AB  - Moderate increases in "classical" biochemical markers of bone turnover have been
      described only in some patients with Camurati-Engelmann disease. However, the
      determination of the following "new" markers has not been previously performed:
      serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal
      propeptide of type I procollagen (PICP), aminoterminal propeptide of type I
      procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide
      carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR),
      crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a
      determination may improve the evaluation of the disease activity. To evaluate the
      usefulness of biochemical markers of bone turnover reflecting Camurati-Engelmann
      disease activity we measured the levels of all these markers in four affected
      patients. The results were compared with bone scintigraphic indices of disease
      activity. Except for PICP and TRAP, bone formation and resorption markers were
      abnormal in all patients and were related to bone scan indices of disease
      activity. Among the markers of bone formation PINP, BAP, and BGP showed the
      highest values, whereas NTX and CL were the most sensitive markers of bone
      resorption. These results suggest that the determination of NTX or CL, and PINP
      or either BAP and BGP, associated with bone scan evaluation, provides the best
      assessment of Camurati-Engelmann disease activity.

PMID- 9192514
TI  - Parathyroid hormone versus phorbol ester stimulation of activator protein-1 gene
      family members in rat osteosarcoma cells.
AB  - We have previously shown that in the rat osteoblastic osteosarcoma cell line-UMR
      106-01-PTH induces maximal collagenase mRNA levels at 4 hours. Since this
      response to PTH requires de novo protein synthesis, it may be mediated by the
      combined temporal expression of members of the activator protein-1 (AP-1) gene
      family. We have demonstrated that maximal mRNA levels of two of the members of
      this family, c-fos and c-jun, occur 30 min after stimulation by PTH. Phorbol
      myristate acetate (PMA) elicits a similar increase in c-fos and c-jun mRNAs, but
      is unable to stimulate transcription of collagenase in these cells. To
      investigate further the involvement of the AP-1 gene family, we examined PTH and
      PMA stimulation of jun-B, jun-D, fos B, and fra-1 mRNAs in UMR 106-01 cells. The
      mRNA for jun-D was abundant under control conditions and showed no variation in
      response to PTH (10(-8) M). The fos B transcripts were not detected under control
      conditions, whereas jun-B and fra-1 mRNAs were present at low basal levels. PTH
      caused an increase in fos B mRNA that reached a maximal 4- to 5-fold plateau
      between 45 and 60 min. An increase in jun-B mRNA in response to PTH was
      detectable at 30 min, but reached a maximal 6- to 7-fold increase at 2 hours.
      After PTH stimulation, the fra-1 transcript showed a 10- to 11-fold peak at 4
      hours. PMA (2.6 x 10(-7) M) stimulated fos B mRNA to maximal abundance at 1 hour,
      similar to PTH. In contrast, PMA caused a maximal increase in jun-B mRNA at 30
      min and fra-1 mRNA at 2 hours, which was earlier than the response to PTH. To
      determine whether an increase in jun-B at the same time as c-fos and c-jun would
      inhibit collagenase gene transcription, we cotransfected an expression vector for
      jun-B with a rat collagenase promoter-reporter gene construct. This resulted in a
      decrease in PTH-stimulation of promoter activity. Thus, it appears that the
      differential temporal stimulation of the AP-1 genes by PTH and PMA, particularly
      an increase in jun-B at the same time as c-fos and c-jun, explains the difference
      seen in their ability to induce transcription of collagenase.

PMID- 9192515
TI  - Inhibition of matrix metalloproteinase-1 by dichloromethylene bisphosphonate
      (clodronate).
AB  - Interstitial collagenase present in human jaw cyst extract and purified human
      fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by
      clodronate, an osteoactive, antiresorptive bisphosphonate. The IC50 of clodronate
      to inhibit MMP-1 is 150 microM. These findings suggest an extended and hitherto
      undescribed properties for clodronate/biphosphonates in prevention and treatment
      of tissue degradation in both bone and soft tissue destructive diseases.

PMID- 9192516
TI  - Comparison of in vitro response to growth hormone by chondrocytes from mandibular
      condyle cartilage of young and old mice.
AB  - In several aspects the features of aging resemble those of the state of growth
      hormone (GH) deficiency. Alterations of bone density and increased incidence of
      osteoporosis are some of the characteristics of aging that are similar to the
      findings in GH-deficient adults. Osteoarthritis (OA), a nonfatal condition
      predominating in old age, is characterized by the slowly progressive destruction
      of articular cartilage of joints. OA lesions are observed in the
      temporomandibular joint of ICR mice aged 7 months and older. The aim of the
      present study was to compare the response of chondrocytes from mandibular condyle
      cartilage of young and old mice to GH and to ascertain whether chondrocytes of
      old animals could still be stimulated to proliferate and to synthesize matrix
      components under the direct effect of GH in vitro. Mandibular condyles from young
      (3-month-old) and old (20-month-old) female ICR mice were cultured up to 72 hours
      in the presence of recombinant rat GH (0.1-100 ng/ml). 3H-Thymidine and 35S
      sulfate were introduced during the last 24 hours of culture. Administration of GH
      appeared to increase only slightly the incorporation of 3H-thymidine in cartilage
      from young compared with the response in cartilage from old animals which was
      much more significant at 24 hours and 48 hours in culture. The same pattern was
      seen for the effect of GH on the incorporation of 35S-sulfate. Cartilage from
      young animals responded only slightly to GH, whereas a significant response was
      observed in cartilage from old animals after 24 and 48 hours in vitro. DNA
      contents were significantly elevated at all time intervals in both old and young
      animals, yet more significantly in cultures from old animals. In contrast, the
      activities of both alkaline and acid phosphatases were elevated at all time
      intervals in cultures from young animals, whereas no induction was observed in
      cultures from old animals. Tissue sections from cultures of old animals treated
      with GH (10 ng/ml, 48 hours) revealed atypical hypertrophic cells along the
      articular surface and also dark staining along the cartilage-bone interface.
      Exposure to tetracycline (10 mg/ml, 24 hours) resulted in an induced
      fluorescence, indicating enhanced mineralization in this region. Results of this
      study indicate that mandibular condyle cartilage from OA old mice responds in
      vitro to the addition of GH via anabolic activities of cell proliferation,
      sulfated proteoglycan synthesis, and possibly enhanced mineralization.

PMID- 9192517
TI  - Mechanism of the morphological changes induced by staurosporine in rat
      osteoblasts.
AB  - Protein kinase C (PKC) plays an important role in the differentiation of cells,
      however, little is known about its relationship to bone metabolism. We have
      previously demonstrated that staurosporine concentration dependently transformed
      the cultured rat osteoblasts into stellate cells. In this study, we further
      investigated the possible mechanisms and significance of the morphological
      changes of osteoblasts induced by staurosporine. The morphological changes
      induced by staurosporine were inhibited by microtubule depolymerizers or elevated
      intracellular calcium, however, actin depolymerizers enhanced the effects of
      staurosporine. Fluorescence labeling showed that staurosporine caused the
      dissolution of the actin microfilaments, but left the microtubules and vimentin
      filaments intact. PKC activators partially antagonized the morphological changes
      induced by staurosporine. Inhibition of protein kinase A or calmodulin-dependent
      kinase is less effective in the induction of stellate cell formation. These
      results suggest that the morphological changes of osteoblasts induced by
      staurosporine may be partly due to PKC inhibition, but other mechanisms may also
      be involved.

PMID- 9192518
TI  - Effect of sodium chloride solutions on mineralized and unmineralized turkey leg
      tendon.
AB  - Previous studies showed that the equatorial diffraction spacing of the collagen
      molecules in mineralized tissues decreases when the tissue is dried and that the
      spacing in totally dried tissue is about the same (1.1 nm) whether mineralized or
      not. Here we report that spacing decreases were observed in both mineralized and
      unmineralized turkey leg tendon after soaking in various sodium chloride
      solutions up to 4.0 M concentration. The effect was seen by X-ray diffraction as
      well as by neutron diffraction. No effect was seen in turkey leg tendon soaked in
      3.0 M ethylene glycol solution. The spacing in unmineralized tissue decreased
      from 1.459 +/- 0.011 nm in 0.15 M saline to 1.403 +/- 0.025 nm in 1.5 M saline, a
      change of 0.056 +/- 0.03 nm or 3.84%. In mineralized turkey leg tendon the
      corresponding spacings were 1.387 +/- 0.012 and 1.321 +/- 0.019 nm, a change of
      0.046 +/- 0.02 nm or 3.4%. No significant dimensional change was noted in the
      thickness even though the equatorial diffraction spacing decreased by 3.4%.
      Electron microscopy showed the collagen fibrils within the mineralized turkey leg
      tendon to be surrounded by highly mineralized material. Presumably the
      composition of the extrafibrillar material is different from the intrafibrillar
      and therefore the extrafibrillar material is a different kind of composite. If it
      is assumed that the extrafibrillar material does not change dimensions
      significantly, then the collagen molecules in the fibrils can be mobile within
      the dimensionally stable cage-like structure.

PMID- 9192520
TI  - Hip fracture-associated mortality reconsidered.

PMID- 9192519
TI  - Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not
      bone strength, in rabbits.
AB  - We hypothesized that fluoride partly acts by changing the levels of circulating
      calcium-regulating hormones and skeletal growth factors. The effects of oral
      fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The
      rabbits were divided into two study groups, one control and the other receiving
      about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of
      fluoride dosing, all rabbits were euthanized and bone and blood samples were
      taken for analyses. Fluoride treatment increased serum and bone fluoride levels
      by over an order of magnitude (P < 0.001), but did not affect body weight or the
      following serum biochemical variables: urea, creatinine, phosphorus, total
      protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal
      fluorosis or osteomalacia was observed histologically, nor did fluoride affect
      serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by
      fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40%
      (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial
      ash weight by 10% (P < 0.05). However, the increases in bone mass and bone
      formation were not reflected in improved bone strength. Fluoride decreased bone
      strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck
      (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in
      fluoride-treated bones (P < 0.001), and there was a negative association between
      crystal width and fracture stress of the femur (P < 0.02). In conclusion,
      fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1
      was increased by fluoride and was associated with increased bone turnover, but
      was not correlated with bone formation markers. High-dose fluoride treatment did
      not improve, but decreased, bone strength in rabbits, even in the absence of
      impaired mineralization.

PMID- 9192537
TI  - Treatment algorithms in child psychopharmacology research.
AB  - Clinical trials in child psychiatry research have increased in complexity.
      Several factors have contributed to this change, including the need to compare
      multiple therapies, to re-create clinically relevant situations in research, to
      standardize treatment approaches, to account for the impact of comorbidity, to
      respond to the needs of individual patients, and to optimize treatment
      accordingly. To preserve the clinical and internal validity of the experimental
      interventions vis-a-vis their increasing complexity, researchers have started
      developing treatment algorithms. These deductive systems for handling data allow
      us to standardize and incorporate clinical judgment into study designs through
      the adoption of a stepwise decision making process. Treatment algorithms are
      different from treatment guidelines. Guidelines are general recommendations that
      apply to groups of patients with certain characteristics; they are not fully
      detailed and are created with the expectation that clinical judgment will be
      applied in individual cases. Algorithms are patient specific, are intended to
      capture all the relevant details of the clinical situation, and require minimal
      clinical judgment for their clinical application; they are designed to minimize
      the role of clinical judgment in research protocols. The entire multistep
      algorithm is tested in a clinical trial, not the single steps that constitute the
      algorithm, so proving the efficacy of an algorithm cannot replace a controlled
      assessment of the individual treatments embedded in the algorithm. Some
      characteristics, properties, and limitations of algorithms in child psychiatry
      and psychopharmacology research are presented along with two examples of
      algorithms currently used in child and adolescent psychopharmacology. Although
      treatment algorithms seldom have been used in pediatric psychiatry and
      psychopharmacology, there are indications that their use will increase in the
      near future and will allow the standardized introduction of clinical judgment
      into research design.

PMID- 9192538
TI  - Sertraline treatment of transition-associated anxiety and agitation in children
      with autistic disorder.
AB  - The intolerance of children with autistic disorder to changes in their routine or
      environment is well known, typically presenting with acute symptoms of anxiety,
      panic, irritability, or agitation. In a clinical sample of children (6-12 years
      old) with autistic disorder and transition-induced behavioral deterioration, 8 of
      9 patients showed a clinically significant improvement in response to sertraline
      treatment. Only one child was taking concurrent psychotropic medication.
      Therapeutic doses were surprisingly low in all cases (25-50 mg daily), with a
      clinical response appearing generally in 2-8 weeks. Adverse effects were minimal
      (one child developed stomachaches), except for apparent sertraline-induced
      behavioral worsening in 2 children when their doses were raised to 75 mg daily.
      In 3 children, an initial satisfactory clinical response appeared to diminish
      after 3-7 months of treatment, despite steady or increased doses. In 6 patients,
      the beneficial effects persisted throughout the several-month follow-up period.
      Only four of the children's families were identified as having mood and/or
      anxiety disorders. This open-label study suggests that short-term sertraline
      treatment may reduce the behavioral reactions seen in association with
      situational transitions or environmental changes in children with autistic
      disorder, though the beneficial effect may be only temporary in some children.
      Our experience suggests that small doses of sertraline may be effective and that
      some children may require divided doses of sertraline during the day. Controlled
      studies are needed to determine the efficacy, safety, and pharmacokinetics of
      sertraline in treating this "need for sameness," both in short-term and long-term
      studies of children with autistic disorder.

PMID- 9192539
TI  - Open fluoxetine treatment of mixed anxiety disorders in children and adolescents.
AB  - An open-label pilot study examined fluoxetine treatment in 16 outpatients (9-18
      years old) with mixed anxiety disorders. Following nonresponse to psychotherapy,
      fluoxetine monotherapy was started at 5 mg daily and was increased weekly by 5 or
      10 mg daily for 6-9 weeks until improvement occurred or to a maximum of 40 mg
      (children under 12) or 80 mg (adolescents). Among patients on fluoxetine,
      severity of illness ratings were "much improved" (mean final Clinical Global
      Impression scale score 2.8 +/- 0.7). Clinical improvement occurred in 10 of 10
      patients with current separation anxiety disorder, 8 of 10 with social phobia, 4
      of 6 with specific phobia, 3 of 5 with panic disorder, and 1 of 7 with
      generalized anxiety disorder. Mean time to improvement was 5 weeks. Mean doses
      were 24 mg (0.7 mg/kg) for children and 40 mg (0.71 mg/kg) for adolescents. Side
      effects were transient and included drowsiness (31% of patients), sleep problems
      (19%), decreased appetite (13%), nausea (13%), abdominal pain (13%), and
      excitement (13%). No patient developed disinhibition, akathisia, or suicidality.
      These preliminary findings suggest fluoxetine effectiveness in separation anxiety
      disorder and social phobia. Youths with only one anxiety disorder appeared to
      respond to lower doses of fluoxetine than patients with multiple anxiety
      disorders (0.49 +/- 0.14 versus 0.80 +/- 0.28 mg/kg, p < 0.05).

PMID- 9192540
TI  - Effects of serotonin reuptake inhibitors on aggressive behavior in
      psychiatrically hospitalized adolescents: results of an open trial.
AB  - Low concentrations of the neurotransmitter serotonin and its 5
      hydroxyindoleacetic acid metabolite in the central nervous system have been
      associated with increased aggressive behavior in animals and humans. Controlled
      clinical trials of serotonin agonists in depressed adults have suggested that
      aggressive behavior is less likely during treatment with these medications than
      with placebo, but there have been no previous studies of selective serotonin
      reuptake inhibitors (SSRIs) and aggression in children. We prospectively followed
      the course of aggressive behavior in 19 psychiatrically hospitalized adolescents
      (not selected for aggressiveness) who received open clinical trials of
      fluoxetine, paroxetine, or sertraline. The patients received standard doses
      (equivalent to fluoxetine 10-40 mg daily) for a minimum of 5 weeks. The starting
      dose was 15 +/- 5 mg, and dosages were raised at a mean rate of 5 mg every 4 days
      up to a mean dose of 25 +/- 10 mg daily. Results from trials of the three SSRIs
      were clustered because the sample sizes were not sufficient for separate
      analyses. Overall, there were no statistically meaningful improvements in the
      level of aggressive behavior, as measured on a modified version of the Overt
      Aggression Scale, over the course of these patients' SSRI trials. Symptoms of
      physical aggression toward others or self were manifest in 12 of the 19 patients
      while on SSRIs. Of the 19 patients, 13 were assessed both on and off SSRIs:
      verbal aggression (p = 0.04), physical aggression toward objects (p = 0.05), and
      physical aggression toward self (p < 0.02) occurred significantly more frequently
      on SSRIs than off; no increase was observed in physical aggression toward others.
      Patients with the highest baseline aggressivity scores did not show greater
      improvement during SSRI treatment. Further research is warranted, particularly to
      explore whether SSRIs may have therapeutic effects on aggression at higher (or
      lower) doses than were administered in this open trial.

PMID- 9192542
TI  - Attenuation of antipsychotic-induced hyperprolactinemia with clozapine.
AB  - Hyperprolactinemia is a well-known consequence of conventional antipsychotic
      therapy. The atypical antipsychotic clozapine is reported to lack this effect. We
      describe a case of attenuated serum prolactin levels after conversion to
      clozapine therapy in an adolescent. A 13-year-old female patient developed
      hyperprolactinemia with galactorrhea and amenorrhea while receiving thioridazine
      300 mg daily. These symptoms continued throughout 3 years of treatment with
      haloperidol 10 mg daily and then fluphenazine 10 mg daily. Subsequently, after an
      incomplete improvement in her psychiatric symptoms and hyperprolactinemia on
      thioridazine 150 mg and bromocriptine 15 mg daily, the patient was changed to
      clozapine at age 16. Clozapine 150 mg twice daily improved her psychiatric status
      and corrected her serum prolactin concentrations after 2 weeks; bromocriptine was
      able to be discontinued. We recommend systematic evaluation of atypical
      neuroleptics as alternative treatments for refractory hyperprolactinemia induced
      by conventional antipsychotics.

PMID- 9192543
TI  - Bait poisoning and why kids complain about their medication.

PMID- 9192541
TI  - Cardiovascular effects of tricyclic antidepressants in childhood asthma: a case
      series and review.
AB  - Children with asthma frequently have significant anxiety and depression that
      interfere with treatment outcome. Although the use of antidepressants may be
      helpful, in the one published study of antidepressant use in pediatric asthma,
      significant side effects necessitated discontinuance; these side effects were
      increased motor activity, impulsive behavior, insomnia, postural hypotension,
      premature auricular contractions, diastolic hypertension, and generalized
      seizure. The objective of this retrospective chart review was to examine whether
      antidepressants could be tolerated and administered safely to children on asthma
      medications. Forty pediatric inpatients (mean age 13.3 years, range 7-19) with
      varying levels of asthma severity (5 mild, 11 moderate, 24 severe) and an average
      duration of asthma treatment of 10.0 years were administered antidepressants
      while also taking an average of 5 medications for asthma (range 2-7). Ten of the
      patients had an additional comorbid medical diagnosis. There were 17 children
      diagnosed with a primary affective disorder; 7 with a primary anxiety disorder;
      and 16 with both an affective and anxiety disorder. Thirty-six children
      ultimately were continued on an antidepressant: 13 on desipramine, 9 on
      nortriptyline, 6 on imipramine, 4 on fluoxetine, 3 on bupropion, and 1 on
      sertraline. Significant cardiovascular side effects (tachycardia, hypertension,
      and postural hypotension) occurred in 4 subjects on tricyclic antidepressants
      (TCAs) and 1 subject on a non-TCA (fluoxetine); 3 of these subjects were able to
      continue treatment with an antidepressant. Two subjects were taken off
      antidepressants because of hypomanic symptoms (increased motor activity, mood
      lability, impulsive behavior, and insomnia). No medications were discontinued
      because of electrocardiogram changes, arrhythmias, or seizures. Doses of TCAs
      were comparable to those in previous studies, but the asthma medications
      differed. Discussion of current anti-asthmatic medications and potential for
      interactions with antidepressants is included.

PMID- 9192544
TI  - The future role for oral exfoliative cytology--bleak or bright?
AB  - The role of exfoliative cytology in the screening for oral cancer has never
      achieved the same success as it has for diagnosing cancer of the uterine cervix.
      Yet the recent application of quantitative and immunocytochemical techniques has,
      to some extent, refined its potential role. However, the absence of a marker,
      present in all malignant lesions but never seen in benign lesions, limits its
      clinical utility and argues for the identification of a combination of markers,
      whose sensitivity and specificity require evaluation. It may well be that oral
      exfoliative cytology will enjoy its greatest success, not so much in screening,
      but rather as providing samples of DNA from biopsy proven oral cancers. Greater
      understanding of the type of mutation present may, in the future, predict not
      only tumour behaviour, but also its response to both traditional and novel forms
      of therapy.

PMID- 9192545
TI  - p53 In biopsies of oral squamous cell carcinoma. A comparative study with a
      malignancy grading system.
AB  - The relationship between the histological grading of malignancy and p53 protein
      expression was studied in 40 biopsies of oral squamous cell carcinomas. An
      immunohistochemical analysis was carried out using the streptavidin method
      preceded by a treatment with citric acid in a microwave oven. All cases were
      classified according to the histological malignancy grading system proposed by
      Anneroth et al. (Scandinavian Journal of Dental Research 1987, 95, 229-249). The
      expression of p53 was found in 62.5% of the carcinomas studied. Positivity of p53
      staining showed a correlation with the histological grade of malignancy and with
      the degree of keratinisation, nuclear polymorphism and number of mitoses.

PMID- 9192546
TI  - Oral Cancer Case Finding Program (OCCFP).
AB  - The aim of the Oral Cancer Case Finding Program (OCCFP) is to reduce the
      morbidity and mortality rates of oral cancer in Cuba. This program is based on
      health education of the whole population and a thorough examination of the oral
      complex, by specially trained stomatologists, of patients attending every
      stomatological care centre. Between 1983 and 1990, 10,167,999 such patients were
      examined country-wide and a total of 30,478 were referred as presenting some sort
      of alteration; 8259 complied with their referral. In this group, 2367
      leucoplakias and 853 other precancerous lesions were diagnosed and treated. These
      3220 premalignancies should have some influence on the cancer morbidity rates.
      Five hundred and eighty-one epidermoid carcinomas and 127 other malignant
      neoplasms were also detected for a total of 708 malignancies. The effectiveness
      of this program can be evaluated by the increments in diagnoses of Stage I oral
      cancer from 22.8% to 48.2% on account of the most advanced stages (II, III and
      IV) which decreased from 77.2% to 51.8%. The object of this paper is to present
      the results of OCCFP up to 1990.

PMID- 9192547
TI  - Assessment of proliferating cell nuclear antigen in nasopharyngeal carcinoma
      tissue and its relation to clinical findings.
AB  - 47 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were studied
      using the proliferating cell nuclear antigen (PCNA) immunostaining technique. The
      results were reproducible as shown by assessment of three separate sections
      performed for each patient. No statistical correlation was found between PCNA
      labelling index (LI) and Ho's clinical staging or time required to achieve
      complete remission of the local disease. A higher PCNA LI was associated with a
      poorer disease-free survival. The literature on the use of PCNA in human tumours
      is reviewed.

PMID- 9192548
TI  - Correlation of lectin binding with lymph node metastasis in oral cancers.
AB  - Lymph node metastasis is an important factor that influences the treatment policy
      and prognosis of oral cancers. The cell membrane is known to play a role in the
      metastatic process. The aim of the present study was to evaluate the relationship
      of lectin binding frequency of oral cancer cells to their capacity to metastasize
      to the lymph node. Smears collected from tumours of 66 untreated patients were
      stained with Jackfruit lectin (JFL) conjugated with horseradish peroxidase (HRP),
      with diaminobenzidine dihydrochloride (DAB) as the visualant. The frequency of
      cells showing lectin binding was evaluated. The results showed that tumours with
      a high frequency of JFL binding cells had higher risk of lymph node metastasis
      (RR = 1.5). It was also found that a combined score integrating the percentage of
      lectin binding cells with known clinical parameters, like primary tumour size,
      local invasion and histological subgroup, had better utility than any of these
      individually in assessing risk of lymph node metastasis. The density of sugar
      residues on the cell surface may be of importance in determining the lymph node
      metastatic potential of oral cancers, and the present study suggests the need for
      further research in this area.

PMID- 9192549
TI  - Ultrastructural morphometry of parotid acinar cells following fractionated
      irradiation.
AB  - The aim of this study was to evaluate the long term effects on the ultrastructure
      of parotid glands after fractionated irradiation. The method implemented involved
      5 x 6 Gy and 5 x 8 Gy, Monday to Friday 6 MV photons. By unilateral irradiation,
      the contralateral parotid gland served as a control. Although irradiation
      diminished the acinar cell density in light microscopic sections from 75 to 32%
      after 5 x 8 Gy of irradiation, ultrastructural morphometry could not detect any
      statistically significant differences in acinar cell size, nuclear size, nuclear
      density, granule area, mean granule size, or granule density. In general, greater
      differences were seen between rats receiving 30 or 40 Gy, on both the irradiated
      and the control size, than between the irradiated side and the control side. This
      was interpreted as due to differences in the nutritional state of the animals.
      This analysis concluded that individual acinar cells that survive irradiation
      seem not to be damaged in the long term when evaluated at the ultrastructural
      level. The study further stresses the importance of adequate sampling sizes and
      the use of adequate controls.

PMID- 9192550
TI  - The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in
      human benign and malignant epithelial lesions of the parotid gland.
AB  - Immunoreactivity of proliferating cell nuclear antigen (PCNA) was assessed in
      formalin-fixed, paraffin-embedded sections from human normal parotid gland (N; n
      = 12), chronic sialadenitis (CS; n = 8), Warthin's tumour (W; n = 10), benign
      pleomorphic adenoma (BPA; n = 11), mucoepidermoid carcinoma (MEC; n = 14),
      carcinoma in pleomorphic adenoma (CPA; n = 10) and adenoid cystic carcinoma (ACC;
      n = 12) of the parotid gland, using the monoclonal antibody PC 10. The
      morphometric parameters measured comprised PCNA labelling induces (PI = the
      numerical percentage of PCNA positive nuclei) and volume densities of PCNA
      positive nuclei(VV, PEP = the relative volume of positive nuclei per unit volume
      of reference epithelium). All parameters were expressed in relation to total
      positive, as well as to strongly- and weakly-positive nuclei. In general, the
      values of PCNA parameters increased progressively in benign lesions in comparison
      with the N group, and in malignant neoplasms in comparison with non-neoplastic
      groups and benign lesions. The strongly-positive parameters showed more
      statistically significant differences than weakly-positive ones, suggesting that
      weakly-stained nuclei may include some non-cycling cells and, therefore, that
      weakly-positive parameters may not be reliable proliferation markers. Values for
      all parameters in CPA were significantly higher than those in BPA, suggesting
      that these parameters may be used as diagnostic discriminators. Spearman rank
      correlation analysis showed a highly positive correlation between the
      morphometric parameters and the severity of the lesions. Furthermore, the mean
      values of PISP were significantly higher in patients who died of the malignant
      tumours than in those patients who survived. Our results indicate that PCNA
      indices might be useful markers for discriminating between benign (BPA) and
      malignant tumours of the parotid gland and that the parameter PISP may have
      prognostic applications.

PMID- 9192551
TI  - Mouth care for nasopharyngeal cancer patients undergoing radiotherapy.
AB  - A randomised trial was undertaken to compare the effect of three oral care
      protocols in delaying the onset of stomatitis and reducing oral injury in
      nasopharyngeal cancer patients undergoing radiotherapy, 30 eligible patients with
      a mean age of 56.2 years were recruited and evenly allocated to one of the three
      groups using a randomly permuted blocks method. Patients allocated to group E1
      and group E2 were given the same instructions on oral care at 1 day, and 1 week
      before radiotherapy, respectively, while those allocated to the control group
      were given no instructions. We use the Oral Assessment Guide to assess the oral
      physical conditions of these patients daily. Our findings revealed that the
      patients in the E2 group not only had later onset of stomatitis than those in the
      control and the E1 groups, but also had lesser degree of oral injury measured by
      the overall assessment score. We thereby recommend the use of the E2 protocol for
      delaying the onset of stomatitis and reducing oral injury in nasopharyngeal
      cancer patients undergoing radiotherapy.

PMID- 9192553
TI  - Transforming growth factor-beta 3 mediated modulation of cell cycling and
      attenuation of 5-fluorouracil induced oral mucositis.
AB  - Mucositis is a common, dose-limiting complication in patients receiving cancer
      chemotherapy, which derives from damage to the epithelial cell layer. We have
      shown that transforming growth factor-beta 3 (TGF-beta 3) negatively regulates
      epithelial cell proliferation and reduces the incidence of oral mucositis. Here,
      we report the findings of a large study examining the effects of TGF-beta 3
      administration in a hamster model on oral epithelial cell cycling in vivo, on
      oral mucositis, on weight retention and on survival. Topical application of TGF
      beta 3 to the buccal mucosa significantly reduced basal cell proliferation, as
      measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and
      DNA ploidy. Administration of topical TGF-beta 3 prior to chemotherapy with 5
      fluorouracil (5-FU) significantly reduced the severity of mucositis with respect
      to time, reduced chemotherapy-associated weight loss and increased survival.

PMID- 9192552
TI  - Correlation between p53 mutation and cyclin D1 amplification in had and neck
      squamous cell carcinoma.
AB  - Mutations in the p53 tumour suppressor gene and amplification of the cyclin D1
      (CCND1) oncogene have been commonly reported in various malignancies. In the
      present study of 39 squamous cell carcinomas of the head and neck, p53 mutations
      were manifest in 11 (28%) of the cases, whereas CCND1 amplification was seen in 6
      (16%) of 37 analysed tumours. The 10 mutations occurring in coding sequences of
      p53 were found in exon 5 (4 cases), exon 6 (3 cases),f and exon 8 (3 cases). No
      mutation was found in exon 7. Eight of the 10 exon nucleotide substitutions were
      missense mutations and two were nonsense mutations. All six tumours with CCND1
      amplification also had p53 mutations, while an additional five tumours manifested
      p53 mutations in the absence of CCND1 amplification. There was a statistically
      significant positive correlation between these two gene alterations. This raises
      the possibility that mutation of p53 precedes CCND1 amplification in
      carcinogenesis.

PMID- 9192554
TI  - Oral tylosis: a re-appraisal.
AB  - The oral lesions in patients with tylosis (palmoplantar keratoderma) associated
      with oesophageal cancer, are evaluated, based on their clinical presentation,
      histological features and long term follow-up. The terminology of these lesions
      is discussed, together with a proposed reclassification of some forms of
      palmoplantar keratoderma.

PMID- 9192555
TI  - Development of squamous cell carcinoma in hepatitis C virus-associated lichen
      planus.
AB  - The hepatitis C virus may occasionally be associated with oral lichen planus. The
      present report details the features of a patient with hepatitis C virus infection
      and oral lichen planus who developed a squamous cell carcinoma of the tongue.

PMID- 9192556
TI  - Simulation modeling: a powerful tool for process improvement.
AB  - Simulation modeling provides an efficient means of examining the operation of a
      system under a variety of alternative conditions. This tool can potentially
      enhance a benchmarking project by providing a means for evaluating proposed
      modifications to the system or process under study.

PMID- 9192557
TI  - Development of an outcomes management program at an academic medical center.
AB  - BACKGROUND: With the advent of managed care, academic medical centers have been
      challenged to lower costs and to document their claims of high quality outcomes.
      A successful method to achieve these objectives must not interfere with the
      academic missions of research and teaching. At M. D. Anderson Cancer Center, we
      initiated a program that would reduce practice variability and increase quality
      with a model that was familiar to the faculty. METHODS: Professional staff
      members were divided into disease site groups that included physicians, nurses,
      and other allied health staff. Each group developed practice guidelines and
      Collaborative Care Paths, based on evidence in the publications and on expert
      opinion. Desired outcomes were prospectively defined during this process. Before
      implementation, paths and guidelines underwent peer review. RESULTS: The faculty
      actively participated in the development and implementation of the program that
      was viewed as a means of empowerment to deal with managed care. Nearly 1000
      patients have been entered on the B8 paths that have been implemented to date.
      CONCLUSION: A physician-driven outcomes management program permits delivery of
      high quality care and supports outcomes research while decreasing cost in an
      academic setting.

PMID- 9192558
TI  - Three alternative methods of developing critical pathways cost and benefits.
AB  - Three common methods of determining optimum pathways and their attendant cost and
      time requirements will be evaluated. Popular methods used for the development and
      adaptation of pathways are the use of published guidelines, the creation of
      pathways within an existing health care system and the use of an automated tool.
      The cost and time required for each of these methods vary tremendously.

PMID- 9192559
TI  - Essential ingredients for a successful hospital-physician partnership.
AB  - Our hospital and a nearby multispecialty physician group practice over- came a
      competitive relationship to become successful partners in meeting the needs of
      the community.

PMID- 9192560
TI  - Effective block scheduling strategies.
AB  - The scheduling of surgery provides opportunities to orchestrate a wide variety of
      resources that have a significant impact on both hospitals, physicians, and
      patients. This article presents the successful development and implementation of
      a block scheduling system in a large operating room setting. Strategies include
      process redesign, automation, and physician empowerment to achieve outcomes of
      improved efficiency, customer satisfaction and physician self-governance.

PMID- 9192561
TI  - Using physician work relative value units to profile surgical packages: methods
      and results for kidney transplant surgery.
AB  - BACKGROUND: This investigation outlines an approach for using the physician work
      relative value units (RVUs) in the Medicare Fee Schedule (MFS) to profile
      physician clinical activities. These techniques were then used to profile the
      physician services associated with kidney transplant patients at Emory University
      System of Health Care. METHODS: All physician services associated with 179
      patients who had kidney transplant surgery in 1993 were studied. By using billing
      data, physician work RVUs were assigned to each service and the results were
      analyzed by type of service and the hospital department providing the service for
      physician work RVUs and physician charges. RESULTS: A mean of 130.4 physician
      work RVUs were involved in the 179 episodes of care. Surgical services
      represented 48.7% of the physician work activity in the kidney transplant. Visit
      and consultative services make up the next highest share with 25.5% of the
      physician work RVUs, whereas anesthesia makes up 13.3% of physician work RVUs.
      Physician charges totaled $16,249 for kidney transplants in 1993 dollars.
      Surgical services accounted for 54.2% of physician charges connected with kidney
      transplants, whereas visits and consultative services represented 20.6% of
      physician charges. CONCLUSIONS: Physician work RVUs in the MFS offer a unique and
      much needed perspective on physician clinical activities. Physician work RVUs are
      an important new tool for healthcare and researchers and their use needs to be
      more fully explored and benchmarks developed for all major medical and surgical
      services.

PMID- 9192562
TI  - Making the transition to critical pathways--a community behavioral health
      center's approach.
AB  - BACKGROUND: Shawnee Hills, Inc., formally began the transition to critical
      pathways in January 1996. The goal was to design and implement a service delivery
      model with clearly defined clinical paths and appropriate and functional
      technical support systems. No specific goal date for full implementation was
      designated; however, the intent was to move into the new system in a manner that
      allowed both consumer and employee participation in the planning process and to
      accommodate the organization's transition from a fee-for-service to a capitated
      model of contracting for services. The target date for completion of phase one,
      research and initial planning, was March 1, 1996. Although there were a number of
      benefits anticipated in adopting the critical paths method (CPM), the primary
      rationale was threefold: (1) standardizing the quality of care and treatment, (2)
      cost containment, and (3) better positioning of the organization for success
      within a capitated funding environment. A review of the publications indicated
      that the CPM had proved to be effective in other healthcare fields. In addition,
      the goals and approaches inherent within the CPM were consistent with the
      organization's total quality management (TQM) philosophy and operational
      practices. METHOD: By using the approach common to the organization since the
      adoption of the principles and practices of TQM in early 1992, a team was
      appointed with the mission of reengineering the clinical services delivery model.
      Unlike previous instances, however, this team was comprised largely of senior
      leadership, and two staff members were assigned on a full-time basis. A more
      detailed review of publications was conducted and, where possible, identification
      of critical pathways developed within the mental health field in other states
      were secured. Focus groups were used to address "best" or "preferred" practices
      for specific populations and age groups. Team members provided an orientation to
      the process, along with the opportunity to critique proposed pathways and models
      for service delivery as they were drafted to all employees through participation
      in ongoing staff development efforts. The center leadership was kept informed and
      was provided additional opportunities for input through regular presentations to
      the Quality Council that meets on a weekly basis. RESULTS: The first phase of the
      transition, research and initial planning, was completed on March 1, 1996. To
      date, the team has adopted or developed initial drafts of proposed clinical
      pathways for frequently occurring diagnoses within adult and child mental health,
      adult and child substance abuse, and specific to early childhood for the mental
      retarded or developmentally delayed. A model for clinical pathways was developed
      incorporating the JCAHO requirements to address assessment, care, and education
      at the major junctures of service delivery. In addition, the team formulated
      recommendations specific to priority areas for each major pathway and the
      approach to be taken in the transition from a fee-for-service to a capitated
      environment. A service delivery model built around acute care and continuing care
      was outlined, but remains a work-in-progress at this time. Finalizing the model
      and the completion of the clinical pathways for specific diagnostic groupings are
      two priorities for the second phase, product development-continued planning and
      transition, now underway. CONCLUSIONS: Although the effort is very much outcomes
      oriented, data are not available at this early stage in the process. (ABSTRACT
      TRUNCATED)

PMID- 9192563
TI  - Benchmarking, monitoring and moving through the continuum of the clinical pathway
      system.

PMID- 9192564
TI  - Flow chart to benchmark.
AB  - BACKGROUND: Benchmarking is the process used to search for best-in-class, compare
      results, discover the enablers of superior process performance, and take action
      to achieve quantum process improvement. It sounds simple, but all too often
      benchmarking efforts fail. The first obstacle often is failing to understand how
      work is currently being performed. METHODS: Through linear flow charts,
      connection charts, and cross-functional flow charts, teams identify each step in
      a process, see how the people in the process interact, follow the work flow, and
      label the type of a step. When this is accompanied by supporting documentation,
      this method provides teams a way to visually see the work flow and know where
      there are glitches and where things are going well. RESULTS: Through flow
      charting, benchmarking teams can understand what they are doing so they know what
      to look for in a benchmarking partner and how to identify the enablers of a
      superior performance. CONCLUSIONS: Without flow charting, teams will not get the
      maximum benefit from benchmarking.

PMID- 9192565
TI  - A clinical path in an acute care hospital.

PMID- 9192566
TI  - Benchmarks of successful physician-hospital organizations.
AB  - In recent years, there have been a proliferation of physician-hospital
      organizations (PHOs) in the medical community across the country. To date, many
      of them have been ineffective with unproven track records. This article will
      explore some of the benchmarks of successful PHOs.

PMID- 9192567
TI  - Factors related to rehospitalization within thirty days of discharge after
      coronary artery bypass grafting.
AB  - BACKGROUND: Early rehospitalization after coronary artery bypass grafting (CABG)
      is an expensive and frequently adverse outcome. Rehospitalization rates after
      various surgical procedures have been used as an indicator of quality of care.
      Determining the extent to which rehospitalization rates reflect patient case mix
      and severity of illness rather than quality of care requires detailed information
      regarding the patients, the care they received, and the reasons for their
      rehospitalization. METHODS: We conducted a nested case control study comparing
      110 CABG patients who were rehospitalized within 30 days after discharge with 224
      control patients. Control patients were randomly selected from patients
      undergoing CABG during the same time frame as the cases and were matched on age,
      gender, and priority of surgery. A detailed chart review provided information
      regarding treatment in the postsurgical period, in addition to the preoperative
      information collected on all CABG patients as part of an ongoing regional
      prospective study. RESULTS: The overall rehospitalization rate was 13.8%. The
      most common reasons for rehospitalization included: wound infection (19%), atrial
      fibrillation (13%), pleural effusion (11%), and thromboembolic event (10%).
      Preoperative severity of illness and comorbidity accounted for 24% of the total
      variance. After adjustment for these factors, discharge hematocrit less than 30%
      (OR = 2.01, p = 0.018) and several discharge medications including:
      antiarrhythmics (OR = 3.26, p = 0.047), diuretics (OR = 2.18, p = 0.055), beta
      blockers (OR = 0.44, p = 0.036), and long length of stay (more than 7 days; OR =
      2.09, p = 0.029) were the most important predictors of rehospitalization risk.
      CONCLUSIONS: Although the reasons for rehospitalization after CABG are
      heterogeneous and related to patient severity of illness as well as comorbid
      status, several of the most common are potentially preventable and related to
      quality of care. Rehospitalization was not related to early discharge.

PMID- 9192568
TI  - Developing clinical program guidelines for subacute care.
AB  - Providers of subacute care are now faced with the reality of demonstrating their
      claims that they offer cost-effective programs. Developing internal standards or
      guidelines from an organizational and clinical perspective can help to assure and
      validate quality service delivery.

PMID- 9192570
TI  - Critical path case management: the headache clinic.
AB  - A practical application of a neurology case management healthcare delivery mode
      results in increased access to specialty providers, shorter follow-up periods,
      and improved continuity of medical care. The program described in the following
      sections was developed at a naval hospital for the ongoing evaluation of
      therapeutic schemes to optimize headache therapy and, 1 year after
      implementation, shows improvement in patient outcomes and resource use.

PMID- 9192569
TI  - Perceived barriers in reporting medication administration errors.
AB  - BACKGROUND: Assuring that medication administration error (MAE) reports are
      reliable and valid is of great significance for the patient, the hospital, and
      the nurse. In most hospitals, MAE reporting relies on the nurse who discovers an
      error to initiate an error report, whether the error was committed by that nurse
      or someone else. Because of the potential for negative consequences, there may be
      significant disincentives for the nurse to report the error. This, the first of
      two articles, describes the results of a large-scale survey designed to assess
      nurses' perceptions of the reasons why MAE may not be reported. The companion
      article compares nurses' estimates of the extent to which MAEs are reported with
      the actual reported medication error rates. METHODS: Nurses in 24 acute-care
      hospitals were surveyed to determine perceptions of reasons why medication errors
      may not be reported. RESULTS: The factor analysis reveals four factors explaining
      why staff nurses may not report medication errors: fear, disagreement over
      whether an error occurred, administrative responses to medication errors, and
      effort required to report MAEs. CONCLUSIONS: There are potential changes in both
      systems and management responses to MAEs that could improve current practice.
      These changes need to take into account the influences of organizational,
      professional, and work group culture.

PMID- 9192571
TI  - Benchmarking patient satisfaction.
AB  - Asking the patient is a critical step-but the format of a patient satisfaction
      survey has a significant impact on your perceptions. Design it carefully.

PMID- 9192572
TI  - Clinical practice guidelines and no-fault programs.

PMID- 9192573
TI  - Clinical practice guidelines: quality improvement tools versus legal norms.
AB  - The role of clinical guidelines in malpractice litigation has been controversial.
      The primary purpose of guidelines as a quality improvement tool must be
      sustained, and applications of guidelines beyond this purpose must be done
      carefully, with full recognition of inherent limitations.

PMID- 9192574
TI  - Risk management issues in benchmarking: a practical perspective on avoiding
      liability exposure.
AB  - Liability exposures may occur from the development, implementation, or misuse of
      benchmarks. Identifying and rectifying risk-prone practices can have a salutary
      effect on limiting such liability exposures.

PMID- 9192575
TI  - Using benchmarking in the hospital environment: a case study.
AB  - As the industry becomes more competitive, many hospitals and other healthcare
      companies are turning to benchmarking to help them make appropriate changes to
      their organizations. Benchmarking allows companies to identify "best practices"
      and make process comparisons with other organizations. The University of
      Cincinnati Hospital is one example of a hospital that has effectively used
      benchmarking for process improvement.

PMID- 9192576
TI  - Benchmarking: a management tool for academic medical centers.
AB  - With a careful cost-restructuring plan based on benchmark information, The Foster
      G. McGaw Hospital of Loyola University reduced its operating budget by $33
      million and put in place the structure for sustained progress in cost reduction.

PMID- 9192577
TI  - The development of The Society of Thoracic Surgeons voluntary national database
      system: genesis, issues, growth, and status.
AB  - BACKGROUND: The purpose of this communication is to demonstrate the feasibility
      of a voluntary national cardiac surgical database. METHODS: The genesis of the
      Society of Thoracic Surgeons (STS) National Cardiac and General Thoracic Surgery
      Databases in the interval of 1986 to 1990 is described. The issues facing the
      Committee in the initial decision making processes are discussed choosing a
      society-based, in-house activity versus using an outside vendor, private practice
      needs versus academic ones; open versus closed membership and vendors, risk
      stratification; data quality; audit; and access to data. RESULTS: In the 6 years
      of operation the STS cardiac surgical database has grown from 41,000 to 706,000
      patients. The number of practice groups, hospitals, and surgeons has increased
      from 26 to 624, 32 to 750, and 120 to 1850, respectively. All but one state is
      represented, as are more than 400 teaching hospitals, including 28 Veterans
      Administration hospitals and 60 university centers. CONCLUSIONS: The STS database
      system has become firmly established and is a model for other societies and
      associations. The data placed yearly in the public domain have become a national
      standard.

PMID- 9192578
TI  - Benchmarking, benchmarks, or best practices? Applying quality improvement
      principles to decrease surgical turnaround time.
AB  - BACKGROUND: The processes of benchmarking, benchmark data comparative analysis,
      and study of best practices are distinctly different. The study of best practices
      is explained with an example based on the Arthur Andersen & Co. 1992 "Study of
      Best Practices in Ambulatory Surgery". METHODS: The results of a national best
      practices study in ambulatory surgery were used to provide our quality
      improvement team with the goal of improving the turnaround time between surgical
      cases. The team used a seven-step quality improvement problem-solving process to
      improve the surgical turnaround time. RESULTS: The national benchmark for
      turnaround times between surgical cases in 1992 was 13.5 minutes. The initial
      turnaround time at St. Joseph's Medical Center was 19.9 minutes. After the team
      implemented solutions, the time was reduced to an average of 16.3 minutes, an 18%
      improvement. Cost-benefit analysis showed a potential enhanced revenue of
      approximately $300,000, or a potential savings of $10,119. CONCLUSIONS: Applying
      quality improvement principles to benchmarking, benchmarks, or best practices can
      improve process performance. Understanding which form of benchmarking the
      institution wishes to embark on will help focus a team and use appropriate
      resources. Communicating with professional organizations that have experience in
      benchmarking will save time and money and help achieve the desired results.

PMID- 9192580
TI  - Establishing a proper perspective on clinical pathways before implementing a
      clinical improvement program.
AB  - The presumed stellar characteristics of clinical pathways have grown in unearthly
      proportions to the extent that our expectations of pathway utilization are
      unrealistic and unfounded. Therefore, before expectations go unmet and
      dissatisfaction with clinical pathway outcomes becomes prevalent, we must
      objectively analyze the clinical pathway phenomenon and understand the origins,
      elements, and purpose of this clinical improvement technique.

PMID- 9192579
TI  - Strategic dislocation: reconsidering the role of benchmarking in the development
      of core competencies.
AB  - American healthcare is under tremendous pressure to make difficult choices to
      stay even with patient and payer expectations. The answer lies not in
      benchmarking incremental improvement alone but in benchmarking the processes to
      nurture core competencies.

PMID- 9192582
TI  - Composing our future: a retrospective and forecast of a specialty practice's
      achievements in a best practice.
AB  - This article documents the practice's achievements resulting from the planning
      efforts and suggests that several key factors, such as establishing and
      communicating a practice direction and empowering and valuing people, resulted in
      the physicians' successful planning.

PMID- 9192581
TI  - The use of support groups among pregnant substance abusers: implications for
      managed care.
AB  - The Better Chance Program offers a model for coordinating managed care for
      pregnant substance abusers. Support groups may prove useful for other high-risk
      segments of society inasmuch as they are enrolled in more restrictive health
      delivery systems.

PMID- 9192583
TI  - The evolution of change: from nurse auditor to clinical reimbursement specialist.
AB  - The nurse auditor's role remains essentially to improve documentation and
      billing, with the commitment to quality improvement.

PMID- 9192584
TI  - Overcoming barriers to benchmarking in healthcare organizations.
AB  - Healthcare organizations can avoid many commonly encountered obstacles to
      benchmarking. Avoiding them requires attention to organization, content area and
      methodologic factors.

PMID- 9192585
TI  - Integrating the physician into the organization decision-making process.
AB  - Physicians need to be involved in organizational decision making, and
      institutional goals are achieved through the integration of operational quality
      committees.

PMID- 9192586
TI  - Recognizing organizational impediments to the total quality management process.
AB  - Continual evaluation of institutional policies and systems can lead to better
      customer service and organizational success through TQM.

PMID- 9192588
TI  - Managed care strategy.
AB  - Managed care is, in reality, managed payment delivered through exclusive price
      competitive contracts that require healthcare providers to reorganize to
      participate as equals in the division of premium dollars.

PMID- 9192587
TI  - Cost containment in cardiac surgery: results with a critical pathway for coronary
      bypass surgery at the New York hospital-Cornell Medical Center.
AB  - PURPOSE: A multidisciplinary project was undertaken at The New York Hospital
      Cornell Medical Center to develop critical pathways for open-heart surgery to
      help reduce cost, shorten hospital length of stay (LOS), and streamline patient
      care. METHODS: A critical pathway for elective coronary artery bypass grafting
      instituted on March 1, 1995, was developed through a cooperative effort involving
      surgeons, anesthesiologists, nurses, social workers, physical therapists,
      nutritionists, and patient case managers. Prospective data collected on
      consecutive patients forming a critical pathway group (n = 114) over a 6-month
      period were compared with retrospective data on consecutive patients forming a
      cohort group (n = 382) who underwent elective coronary artery bypass grafting in
      1994. RESULTS: The critical pathway group of patients experienced a significantly
      shorter total hospital LOS (7.7 +/- 2.3 days vs 11.1 +/- 6 days, p < 0.0001) and
      shorter intensive care unit LOS (1.5 +/- 0.9 days vs 2.0 +/- 2.8 days, p <
      0.0001). Direct costs were computed by use of hospital charges multiplied by the
      Medicare cost-to-charge ratio. Mean hospital direct cost (ancillary resources)
      was $1181 lower in the critical pathway group when compared with the control
      group (p < 0.0001). The postoperative mortality and readmission rates were
      similar for the two groups of patients. CONCLUSIONS: The ongoing analysis of
      cost, LOSs, and outcomes has made possible a process of continuous quality
      improvement on the cardiothoracic service in which further areas for improvement
      are identified and studied. The use of a critical pathway for elective coronary
      artery bypass grafting at our institution significantly reduced hospital LOS and
      direct costs while maintaining the overall quality of patient care.

PMID- 9192589
TI  - The challenge of benchmarking: surgical volume and operative mortality in
      Veterans Administration Medical Centers.
AB  - BACKGROUND: This study examines the relationship between hospital surgical volume
      and operative modality rate. Emphasis is placed on the role of referral patterns;
      the effects of variation in patient condition, operative procedures, and hospital
      characteristics, and the contribution of volume of related procedures, in
      addition to specific-procedure volume, the definition of operative mortality, and
      their influence on surgical outcome. METHODS: This cohort study included all
      Department of Veterans Affairs Medical Centers with surgery programs. All
      patients in five operation-diagnosis sets (colectomy for cancer, colectomy
      without cancer, amputation above the knee, coronary artery bypass grafting for
      old myocardial infarction, and open-heart valvuloplasty), discharged from 1987
      through 1989, were assessed to determine the risk-adjusted 30-day postoperative
      morality rate. RESULTS: Only one of the studied groups, valvuloplasty,
      demonstrated a significant inverse relationship between hospital surgical volume
      and operative mortality rate. No additional effect on outcome owing to related
      procedure volume was noted. CONCLUSIONS: This study demonstrates some of the
      difficulties in assessing surgical results and that we should be skeptical of the
      intuitively attractive notion that high annual volumes of operations will
      necessarily result in improved outcomes. This is congruent with recent literature
      in which there is no broad-based evidence that hospital surgical volume affects
      operative mortality rate.

PMID- 9192590
TI  - Best practice: clinical pathways for uncomplicated births.
AB  - BACKGROUND: A level II hospital with births exceeding 2000 annually was
      challenged by managed care companies to develop high-quality, cost-effective, and
      clinically efficient obstetric and newborn care under the constraints of a
      reduced length of stay. METHODS: As a result of the challenge, clinical pathways
      were initiated for vaginal and cesarean section births and for normal newborns.
      RESULTS: Successful implementation of the clinical pathways has decreased the
      average length of stay for uncomplicated deliveries from 2.02 to 1.67 days and
      for normal newborns from 1.99 to 1.43 days. CONCLUSIONS: Data from quality
      outcome indicators that measure the rate of occurrence of emergency department
      admissions or hospital readmissions for either mother or newborn within 14 days
      of birth reveal no increase in either variance since the clinical pathways were
      implemented.

PMID- 9192591
TI  - Assessing facility and space resources in an academic health science center: a
      process that works.
AB  - BACKGROUND: The authors served as external consultants to an academic health
      science center in the eastern United States to identify current and future space
      needs in response to reported deficiencies, especially in the medical school.
      This work established a framework to identify, prioritize, and plan future
      facility and space improvement projects. METHODS: The authors used several
      methods to quantify and profile current space needs and future space
      requirements, including data and plan reviews, surveys and questionnaires, and on
      site facility tours and inspections. Most important, the consultants brought
      their collective experience as well as their proprietary planning database and
      guidelines to formulate findings and develop practical recommendations. RESULTS:
      The engagement substantiated faculty's concerns and perceptions that additional
      space was necessary for many existing programs, especially the medical school.
      However, specific space needs, by department or program, frequently differed from
      faculty's perceived needs as well as those of the university administration.
      CONCLUSIONS: Several important conclusions dealt with the client's need to
      develop and formalize the space planning and management process. Appropriate
      guidelines for space planning purposes for this academic health science center
      also were identified as were the "next steps" to build on this successful study.

PMID- 9192592
TI  - The impact of restructuring and work design on nursing practice and patient care.
AB  - The purpose of this study was to examine if registered nurses' (RNs) reports of
      the structure, work processes and performance of Massachusetts hospitals have
      changed over a five year period. Responses of 928 randomly selected RNs surveyed
      in 1989 and 858 randomly selected RNs in 1994 to the RN Quality of Worklife
      Survey (RNQOWS) were compared. Data analysis was performed with a between
      subjects multivariate analysis of covariance, controlling for number of years as
      an RN and as a member of a collective bargaining unit. Significant differences
      were found in the variables that measure human resources, administrative
      motivating conditions, task effectiveness, and efficiency (p < 0.001). The
      implications of the findings for nursing practice in hospitals is discussed and
      recommendations are made for further research.

PMID- 9192593
TI  - Measuring the performance of behavioral healthcare organizations: a proposed
      model.
AB  - Practitioners in the field of behavioral healthcare are under increasing pressure
      to demonstrate the effective and efficient delivery of services. While there are
      a variety of models that provide important elements of a framework for defining
      and measuring organizational performance, few appear to integrate the unique
      perspectives of all the organization's key constituent or customer groups.

PMID- 9192594
TI  - Outcomes and benchmarks in the home medical equipment services industry: the time
      is now.
AB  - The home medical equipment services industry has started to participate in
      outcomes measurement and benchmarking. As a result, the industry now will be able
      to capture and to compare treatment, performance, and outcome data to make
      informed decisions about the benefit and the value of various options to treat
      illness or to maintain wellness in the home setting.

PMID- 9192595
TI  - A new use for focus groups--building and empowering a culturally diverse team.
AB  - BACKGROUND: The success of a cultural diversity training program in an acute care
      health facility was due in large part to the use of the focus group method.
      METHOD: This method enabled us to identify sensitive issues to be addressed in
      educational programs for staff. Some of the criteria for successful use of the
      focus group method applied to our situation. RESULT: We found that much of the
      traditional wisdom did not necessarily apply in a diversity program. CONCLUSION:
      Several additional benefits such as ethnic group empowerment and the enhancement
      of a more team-oriented approach made use of the focus group method a very
      worthwhile venture for this project.

PMID- 9192596
TI  - Improving laboratory results turnaround time.
AB  - BACKGROUND: Physicians need prompt results of laboratory tests before early
      morning rounds or on a stat basis to support time-critical decisions that can
      impact patient care or length of stay. At The Methodist Hospital, we formed a
      multidisciplinary performance improvement team that was successful in reducing
      the length of time between collection of specimen and availability of laboratory
      test results (turnaround time). Our goals were to have Stat results available in
      less than 60 minutes, and results for morning blood tests available by 8 AM for
      acute care units and 7 AM for critical care units. METHODS: Before making
      changes, we first devised a system of measurement. The most efficient way to
      obtain data was to query the mainframe laboratory information system for times of
      specimen collection, times for reception in the laboratory, and times for results
      verification. We also decided that patient-specific information on specimens that
      did not meet the goals-exceptions-would be crucial for effective follow-up and
      corrective action. During several measurement and assessment cycles, we
      identified opportunities to improve our process. RESULTS: The percentage of early
      morning specimens meeting the specified turnaround time improved from 60% in
      August 1995, to greater than 90% in May 1996. The average turnaround time for
      early morning specimens takes only 95 minutes rather than 186 minutes. The
      average turnaround time for a stat specimen declined from 69 minutes to 45
      minutes during this process. The volume of stat specimens has also declined
      significantly. CONCLUSION: Laboratory test results turnaround time is impacted by
      a variety of health-care providers, and a multidisciplinary team can work
      together to improve prompt availability of test results to support time-critical
      decisions.

PMID- 9192597
TI  - Building effective working relationships with healthcare executives.
AB  - Managed care challenges physicians to learn to collaborate with healthcare
      executives to achieve cost containment while enhancing quality of patient care.
      This report describes specific steps to successful working relationships between
      physicians and healthcare executives. "Learning the culture," recognizing
      differences, offering assistance, taking steps toward closer collaboration, and
      avoiding pitfalls are interpersonal skills and behaviors that allow physicians to
      become part of the decision process in a managed care environment.

PMID- 9192598
TI  - Predicting surgical outcome for pain relief and return to work.
AB  - BACKGROUND: We evaluated a new psychological test (Paindex) for identifying and
      quantifying psychological factors associated with poor surgical outcome, and
      predicting the degree of pain relief and return to work. METHOD: This test was
      administered to 120 randomly selected patients before carpal tunnel and
      laminectomy surgeries. RESULTS: This test correctly predicted the probability of
      pain relief and return to work in 46 of the 50 laminectomy patients (92%), and 63
      of the 70 carpal tunnel patients (90%). The overall test sensitivity was 86% and
      the specificity 94%. CONCLUSION: These findings indicate that this can be a
      useful adjunctive test for identifying psychological problems that could have a
      bearing on the decision to operate and then problems that could occur after
      surgery, particularly in cases where the extent and degree of pain and disability
      are judged to be considerably in excess of the objective medical findings.

PMID- 9192599
TI  - Developing an economic model to reduce costs in a reengineered hospital
      environment.
AB  - In its recent reengineering efforts, the Mount Sinai Hospital developed economic
      tools to assure that this major restructuring project would reach its
      predetermined financial objectives. We discuss how these tools were designed and
      implemented and what impact they had.

PMID- 9192600
TI  - Building effective working relationships with healthcare executives.
AB  - Managed care challenges physicians to learn to collaborate with healthcare
      executives to achieve cost containment while enhancing quality of patient care.
      This report describes specific steps to successful working relationships between
      physicians and healthcare executives. "Learning the culture," recognizing
      differences, offering assistance, taking steps toward closer collaboration, and
      avoiding pitfalls are interpersonal skills and behaviors that allow physicians to
      become part of the decision process in a managed care environment.

PMID- 9192601
TI  - Benchmarking surgeon satisfaction at academic health centers: a nationwide
      comparative survey.
AB  - BACKGROUND: Forty-six academic health centers (AHCs) belonging to the University
      HealthSystem consortium joined forces to compare the efficiency of their surgical
      services and to identify best practices. In addition to measures of operational
      performance, surgeon satisfaction with the surgical services provided was
      measured by using a standardized questionnaire. METHODS: From hospital records,
      indicators of the efficiency of surgical services were collected in three main
      areas: scheduling, preoperative testing and assessment, and the intraoperative
      process. Responding to a mail questionnaire, a sample of surgeons rated their
      satisfaction with key aspects of surgical services including scheduling,
      operating room staff, and equipment/supplies. On the basis of a review of the
      operational measures and the survey results, high performers were identified.
      Site visits were made to several of these high performers to uncover the critical
      factors responsible for their success. RESULTS: The survey revealed distinct
      variations in surgeon satisfaction across the participating institutions.
      Numerical benchmarks were obtained for surgeon satisfaction with each key
      component of surgical services. Scheduling was the most important component of
      overall surgeon satisfaction, explaining 71% of the variance in the rating of
      overall satisfaction with surgical services. High operational efficiency and high
      surgeon satisfaction were not incompatible. Several of the participating
      institutions were able to achieve both. These results were disseminated to all of
      the participants at a national meeting as well as in written form. CONCLUSIONS:
      The surgeon satisfaction survey allowed the participants to establish benchmarks
      for surgeon satisfaction for each key component of the surgical services they
      receive. The site visits revealed several common characteristics of highly
      efficient surgical services. Taken by themselves, the participating institutions
      might have been reluctant to consider adopting these best practices for fear of
      alienating the surgical staff. The availability of data on surgeon satisfaction
      showed the participants that these best practices can coexist with high levels of
      surgeon satisfaction. This has helped to promote their adoption by the other
      participating institutions.

PMID- 9192602
TI  - Statistical approaches to outcomes assessment.
AB  - BACKGROUND: Statistical methods and software can be useful for evaluating
      clinical outcomes data. METHOD: The use of control charts and regression analysis
      can be particularly helpful in outcomes assessment. Control charts can reveal
      outlier events and patterns that require additional review leading to changes
      that improve outcomes. Regression analysis can show factors that affect process
      characteristics. This article uses examples derived from hospital outcomes
      assessment activities relating to length of stay, treatment planning, insurance
      coverage, patient characteristics, and clinical decision making. RESULTS: Minitab
      statistical software is used to create control charts and perform regression
      analysis, and essential Minitab commands are explained. CONCLUSION: Through the
      use of the techniques described the clinical and manager can more effectively
      evaluate clinical outcomes data to improve healthcare quality.

PMID- 9192603
TI  - Launching a self-assessment process for systems integration: framework and
      findings.
AB  - The National Chronic Care Consortium developed the SASI tool to help health-care
      networks plan, implement, and measure chronic care integration across their full
      continuums of care. An integrated network for chronic care can be applied to any
      care population, and the SASI tool can assist in integration efforts in a variety
      of circumstances.

PMID- 9192604
TI  - Predicting surgical outcome for pain relief and return to work.
AB  - BACKGROUND: We evaluated a new psychological test (Paindex) for identifying and
      quantifying psychological factors associated with poor surgical outcome, and
      predicting the degree of pain relief and return to work. METHOD: This test was
      administered to 120 randomly selected patients before carpal tunnel and
      laminectomy surgeries. RESULTS: This test correctly predicted the probability of
      pain relief and return to work in 46 of the 50 laminectomy patients (92%), and 63
      of the 70 carpal tunnel patients (90%). The overall test sensitivity was 86% and
      the specificity 94%. CONCLUSION: These findings indicate that this can be a
      useful adjunctive test for identifying psychological problems that could have a
      bearing on the decision to operate and then problems that could occur after
      surgery, particularly in cases where the extent and degree of pain and disability
      are judged to be considerably in excess of the objective medical findings.

PMID- 9192605
TI  - Clinical pathway for pneumonia: development, implementation, and initial
      experience.
AB  - BACKGROUND: As part of a large multidisciplinary project to reduce cost, decrease
      hospital length of stay, and improve efficiency of patient care at Saint Mary's
      Hospital, a clinical pathway for pneumonia was developed and implemented.
      METHODS: After using analysis of severity-adjusted data to determine which
      conditions would be best targets for improvement, a utilization management
      steering committee created a multidisciplinary group to develop a clinical
      pathway for pneumonia. This group was led by physician champions and consisted of
      representatives from nursing, respiratory therapy, pharmacy, and home healthcare.
      With information gained from chart abstraction, which identified "best practice"
      patterns, guidance from the medical literature, and local expertise, this group
      developed a clinical pathway that included an auxiliary protocol for respiratory
      care and a detailed educational brochure for patients. Before implementing the
      clinical pathway, extensive educational activities were undertaken involving the
      medical staff, house staff, nurses, and other staff. Data collected on
      consecutive patients discharged after implementation of the pathway were compared
      with data collected on patients discharged before the pathway in 1994. RESULTS:
      For DRG 89, the patients who were on the pathway in comparison to the control
      patients from 1994 had a lower average length of stay by 1.45 days (5.84 vs. 7.29
      days) and a lower average total charge by $1,453 ($9,511 vs. $10,964). For DRG
      90, the patients who were on the pathway in comparison to the control patients
      from 1994 had a lower average length of stay by 1.83 days (3.45 vs. 5.28 days)
      and a lower average total charge by $1319 ($5450 vs. $6769). CONCLUSIONS: The
      pneumonia clinical pathway that was implemented was associated with reductions in
      the length of stay and total charges. These reductions were seen in relationship
      to historical controls and to patients cared for concurrently who were not placed
      on the pathway. Although not fully used on all pneumonia patients, the presence
      of the pathway probably had some positive effects even on patients not formally
      on the pathway, through systems changes and educational influences. The pathway
      also positively influenced other conditions by the use of ancillary algorithms
      for conditions other than pneumonia, and the more rapid administration of
      antibiotics for other infectious diseases. Also, lessons learned in the creation
      of this first pathway have been helpful in streamlining the process of future
      pathway development.

PMID- 9192606
TI  - Benchmarking: a case report.
AB  - In mid 1993, administrators and physicians at Bristol Medical Center teams up
      with HCIA to perform clinical pathway analysis on five diagnosis related groups.
      The major goal of this project was to establish a partnership between the
      hospital administration and the medical staff to meet or beat existing
      benchmarks.

PMID- 9192609
TI  - Nonenzymatic and enzymatic hydrolysis of alkyl halides: a theoretical study of
      the SN2 reactions of acetate and hydroxide ions with alkyl chlorides.
AB  - The SN2 displacements of chloride ion from CH3Cl, C2H5Cl, and C2H4Cl2 by acetate
      and hydroxide ions have been investigated, using ab initio molecular orbital
      theory at the HF/6-31+G(d), MP2/6-31+G(d), and MP4/6-31+G(d) levels of theory.
      The central barriers (calculated from the initial ion-molecule complex) of the
      reactions, the differences of the overall reaction energies, and the geometries
      of the transition states are compared. Essential stereochemical changes before
      and after the displacement reactions are described for selected cases. The gas
      phase reactions of hydroxide with CH3Cl, C2H5Cl, and C2H4Cl2 have no overall
      barrier, but there is a small overall barrier for the reactions of acetate with
      CH3Cl, C2H5Cl, and C2H4Cl2. A self-consistent reaction field solvation model was
      used to examine the SN2 reactions between methyl chloride and hydroxide ion and
      between 1,2-dichloroethane and acetate in solution. As expected, the reactions in
      polar solvent have a large barrier. However, the transition state structures
      determined by ab initio calculations change only slightly in the presence of a
      highly polar solvent as compared with the gas phase. We also calibrated the PM3
      method for future study of an enzymatic SN2 displacement of halogen.

PMID- 9192612
TI  - Peptidyl-transferase inhibitors have antiviral properties by altering programmed 
      1 ribosomal frameshifting efficiencies: development of model systems.
AB  - The effects of two peptidyl-transferase inhibitors, anisomycin and sparsomycin,
      on ribosomal frameshifting efficiencies and the propagation of yeast double
      stranded RNA viruses were examined. At sublethal doses in yeast cells these drugs
      specifically alter the efficiency of -1, but not of +1, ribosomal frameshifting.
      These compounds promote loss of the yeast L-A double-stranded RNA virus, which
      uses a programmed -1 ribosomal frameshift to produce its Gag-Pol fusion protein.
      Both of these drugs also change the efficiency of -1 ribosomal frameshifting in
      yeast and mammalian in vitro translation systems, suggesting that they may have
      applications to control the propagation of viruses of higher eukaryotes, which
      also use this translational regulatory mechanism. Our results offer a new set of
      antiviral agents that may potentially have a broad range of applications in the
      clinical, veterinary, and agricultural fields.

PMID- 9192613
TI  - The heat shock-induced hyperphosphorylation of tau is estrogen-independent and
      prevented by androgens: implications for Alzheimer disease.
AB  - We have shown that heat shock induces rapid dephosphorylation of tau in both
      female and male rats followed by hyperphosphorylation only in female rats. To
      investigate the role of gonadal hormones, rats were ovariectomized (OVX),
      orchiectomized (ORX), or sham-gonadectomized and received replacement therapy
      with estradiol benzoate (EB), testosterone propionate (TP), or sesame oil (SO)
      vehicle for 2-3 weeks, respectively. At 0, 3, 6, and 12 hr after heat shock,
      immunoblot analysis of SDS cerebral extracts was performed using phosphate
      dependent and -independent anti-tau antibodies. Seven groups of rats were
      analyzed: (i) sham-OVX + SO; (ii) OVX + SO; (iii) OVX + EB; (iv) sham-ORX + SO;
      (v) ORX + SO; (vi) ORX + TP; and (vii) ORX. In all seven groups, there was
      dephosphorylation of tau at 0 hr after heat shock. In all three groups of female
      rats, there was hyperphosphorylation of tau at 3 hr after heat shock, and its
      degree and temporal pattern were identical between the OVX + SO and OVX + EB
      groups. In male rats, there was hyperphosphorylation of tau at 3 hr after heat
      shock in both ORX + SO and ORX groups, and its degree was reduced in the ORX + TP
      group. Thus, dephosphorylation of tau is gonadal hormone-independent, but while
      its hyperphosphorylation is estrogen-independent it is prevented by androgens.
      Because tau is abnormally hyperphosphorylated in Alzheimer disease, which is more
      frequent in women than men, these findings suggest that androgens may exert a
      neuroprotective effect.

PMID- 9192614
TI  - Prion-inducing domain 2-114 of yeast Sup35 protein transforms in vitro into
      amyloid-like filaments.
AB  - The yeast non-Mendelian genetic factor [PSI], which enhances the efficiency of
      tRNA-mediated nonsense suppression in Saccharomyces cerevisiae, is thought to be
      an abnormal cellular isoform of the Sup35 protein. Genetic studies have
      established that the N-terminal part of the Sup35 protein is sufficient for the
      genesis as well as the maintenance of [PSI]. Here we demonstrate that the N
      terminal polypeptide fragment consisting of residues 2-114 of Sup35p, Sup35pN,
      spontaneously aggregates to form thin filaments in vitro. The filaments show a
      beta-sheet-type circular dichroism spectrum, exhibit increased protease
      resistance, and show amyloid-like optical properties. It is further shown that
      filament growth in freshly prepared Sup35pN solutions can be induced by seeding
      with a dilute suspension of preformed filaments. These results suggest that the
      abnormal cellular isoform of Sup35p is an amyloid-like aggregate and further
      indicate that seeding might be responsible for the maintenance of the [PSI]
      element in vivo.

PMID- 9192615
TI  - An extended DNA structure through deoxyribose-base stacking induced by RecA
      protein.
AB  - The family of proteins that are homologous to RecA protein of Escherichia coli is
      essential to homologous genetic recombination in various organisms including
      viruses, bacteria, lower eukaryotes, and mammals. In the presence of ATP (or
      ATPgammaS), these proteins form helical filaments containing single-stranded DNA
      at the center. The single-stranded DNA bound to RecA protein is extended 1.5
      times relative to B-form DNA with the same sequence, and the extension is
      critical to pairing with homologous double-stranded DNA. This pairing reaction,
      called homologous pairing, is a key reaction in homologous recombination. In this
      NMR study, we determined a three-dimensional structure of the single-stranded DNA
      bound to RecA protein. The DNA structure contains novel deoxyribose-base stacking
      in which the 2'-methylene moiety of each deoxyribose is placed above the base of
      the following residue, instead of normal stacking of adjacent bases. As a result
      of this deoxyribose-base stacking, bases of the single-stranded DNA are spaced
      out nearly 5 A. Thus, this novel structure well explains the axial extension of
      DNA in the RecA-filaments relative to B-form DNA and leads to a possible
      interpretation of the role of this extension in homologous pairing.

PMID- 9192617
TI  - The rational design and construction of a cuboidal iron-sulfur protein.
AB  - Rational protein design is an emerging approach for testing general theories of
      protein chemistry through the creation of new structures and functions. Here we
      present the first successful introduction by rational design of a [Fe4S4]
      cuboidal cluster into the hydrophobic core of Escherichia coli thioredoxin, a
      protein normally devoid of metal centers. Cuboidal [Fe4S4] is one of the stable
      forms of self-assembled iron-sulfur clusters that are thought to represent some
      of the earliest evolved biological redox centers. [Fe4S4] clusters have been
      recruited for use in a variety of proteins whose functions are central to many of
      the major biochemical processes ranging from simple soluble electron-transfer
      agents, to membrane-bound components of electron-transfer chains, to electron
      reservoirs in complex metalloenzymes such as nitrogenase. By situating an [Fe4S4]
      cluster into a protein environment not previously adapted by evolution we can
      explore the factors by which their activity is modulated by the protein matrix.

PMID- 9192616
TI  - Covalent modification of the active site threonine of proteasomal beta subunits
      and the Escherichia coli homolog HslV by a new class of inhibitors.
AB  - The proteasome is a multicatalytic protease complex that plays a key role in
      diverse cellular functions. The peptide vinyl sulfone, carboxybenzyl-leucyl
      leucyl-leucine vinyl sulfone (Z-L3VS) covalently inhibits the trypsin-like,
      chymotrypsin-like and, unlike lactacystin, also the peptidylglutamyl peptidase
      activity in isolated proteasomes, and blocks their function in living cells.
      Although described as a class of mechanism-based inhibitors for cysteine
      proteases, the peptide vinyl sulfone Z-L3VS and a 125I-labeled nitrophenol
      derivative (125I-NIP-L3VS) covalently modify the active site threonine of the
      catalytic beta subunits of the proteasome. Modification of Thermoplasma
      proteasomes demonstrates the requirement for a hydroxyl amino acid (threonine,
      serine) as nucleophile at the beta subunit's NH2 terminus. 125I-NIP-L3VS
      covalently modifies the HslV subunit of the Escherichia coli protease complex
      HslV/HslU, a reaction that requires ATP, and supports a catalytic mechanism
      shared with that of the eukaryotic proteasome.

PMID- 9192618
TI  - Modular organization of the catalytic center of RNA polymerase.
AB  - The Fe2+ ion that specifically replaces Mg2+ in the active center of RNA
      polymerase generates reactive hydroxyl radicals that cause highly localized
      cleavage of polypeptide chains. Mapping of the cleavage sites revealed the
      overall architecture of the active center. Nine distinct sites, five in the beta
      subunit and four in the beta' subunit of Escherichia coli RNA polymerase, all at
      or near highly conserved sequence motifs, are brought together in the enzyme's
      ternary structure within the distance of approximately 1 nm from the active
      center Me2+. These sites are located in at least six different domains of the
      subunits, reflecting modular organization of the active center.

PMID- 9192619
TI  - Defective prohormone processing and altered pancreatic islet morphology in mice
      lacking active SPC2.
AB  - The prohormone convertase SPC2 (PC2) participates in the processing of
      proinsulin, proglucagon, and a variety of other neuroendocrine precursors, acting
      either alone or in conjunction with the structurally related dense-core granule
      convertase SPC3 (PC3/PC1). We have generated a strain of mice lacking active SPC2
      by introducing the neomycin resistance gene (Neor) into the third exon of the
      mSPC2 gene. This gene insertion results in the synthesis of an exon 3-deleted
      form of SPC2 that does not undergo autoactivation and is not secreted. The
      homozygous mutant mice appear to be normal at birth. However, they exhibit a
      small decrease in rate of growth. They also have chronic fasting hypoglycemia and
      a reduced rise in blood glucose levels during an intraperitoneal glucose
      tolerance test, which is consistent with a deficiency of circulating glucagon.
      The processing of proglucagon, prosomatostatin, and proinsulin in the alpha,
      delta, and beta cells, respectively, of the pancreatic islets is severely
      impaired. The islets in mutant mice at 3 months of age show marked hyperplasia of
      alpha and delta cells and a relative diminution of beta cells. SPC2-defective
      mice offer many possibilities for further delineating neuroendocrine precursor
      processing mechanisms and for exploring more fully the physiological roles of
      many neuropeptides and peptide hormones.

PMID- 9192620
TI  - Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli
      single-stranded DNA-binding protein determined by multiwavelength x-ray
      diffraction on the selenomethionyl protein at 2.9-A resolution.
AB  - The crystal structure of the tetrameric DNA-binding domain of the single-stranded
      DNA binding protein from Escherichia coli was determined at a resolution of 2.9 A
      using multiwavelength anomalous dispersion. Each monomer in the tetramer is
      topologically similar to an oligomer-binding fold. Two monomers each contribute
      three beta-strands to a single six-stranded beta-sheet to form a dimer. Two dimer
      dimer interfaces are observed within the crystal. One of these stabilizes the
      tetramer in solution. The other interface promotes a superhelical structure
      within the crystal that may reflect tetramer-tetramer interactions involved in
      the positive cooperative binding of the single-stranded DNA-binding protein to
      single-stranded DNA.

PMID- 9192621
TI  - c-Myc transactivation of LDH-A: implications for tumor metabolism and growth.
AB  - Cancer cells are able to overproduce lactic acid aerobically, whereas normal
      cells undergo anaerobic glycolysis only when deprived of oxygen. Tumor aerobic
      glycolysis was recognized about seven decades ago; however, its molecular basis
      has remained elusive. The lactate dehydrogenase-A gene (LDH-A), whose product
      participates in normal anaerobic glycolysis and is frequently increased in human
      cancers, was identified as a c-Myc-responsive gene. Stably transfected Rat1a
      fibroblasts that overexpress LDH-A alone or those transformed by c-Myc
      overproduce lactic acid. LDH-A overexpression is required for c-Myc-mediated
      transformation because lowering its level through antisense LDH-A expression
      reduces soft agar clonogenicity of c-Myc-transformed Rat1a fibroblasts, c-Myc
      transformed human lymphoblastoid cells, and Burkitt lymphoma cells. Although
      antisense expression of LDH-A did not affect the growth of c-Myc-transformed
      fibroblasts adherent to culture dishes under normoxic conditions, the growth of
      these adherent cells in hypoxia was reduced. These observations suggest that an
      increased LDH-A level is required for the growth of a transformed spheroid cell
      mass, which has a hypoxic internal microenvironment. Our studies have linked c
      Myc to the induction of LDH-A, whose expression increases lactate production and
      is necessary for c-Myc-mediated transformation.

PMID- 9192622
TI  - Bipartite substrate discrimination by human nucleotide excision repair.
AB  - Mammalian nucleotide excision repair (NER) eliminates carcinogen-DNA adducts by
      double endonucleolytic cleavage and subsequent release of 24-32 nucleotide-long
      single-stranded fragments. Here we manipulated the deoxyribose-phosphate backbone
      of DNA to analyze the mechanism by which damaged strands are discriminated as
      substrates for dual incision. We found that human NER is completely inactive on
      DNA duplexes containing single C4'-modified backbone residues. However, the same
      C4' backbone variants, which by themselves do not perturb complementary hydrogen
      bonds, induced strong NER reactions when incorporated into short segments of
      mispaired bases. No oligonucleotide excision was detected when DNA contained
      abnormal base pairs without concomitant changes in deoxyribose-phosphate
      composition. Thus, neither C4' backbone lesions nor improper base pairing
      stimulated human NER, but the combination of these two substrate alterations
      constituted an extremely potent signal for double DNA incision. In summary, we
      used C4'-modified backbone residues as molecular tools to dissect DNA damage
      recognition by human NER into separate components and identified a bipartite
      discrimination mechanism that requires changes in DNA chemistry with concurrent
      disruption of Watson-Crick base pairing.

PMID- 9192623
TI  - Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the
      Drosophila discs large tumor suppressor protein.
AB  - The 9ORF1 gene encodes an adenovirus E4 region oncoprotein that requires a C
      terminal region for transforming activity. Screening a lambdagt11 cDNA expression
      library with a 9ORF1 protein probe yielded a novel cellular PDZ domain-containing
      protein, 9BP-1, which binds to wild-type, but not a transformation-defective, C
      terminal, mutant 9ORF1 protein. The fact that PDZ domains complex with specific
      sequences at the free C-terminal end of some proteins led to the recognition that
      the 9ORF1 C-terminal region contained such a consensus-binding motif. This
      discovery prompted investigations into whether the 9ORF1 protein associates with
      additional cellular proteins having PDZ domains. It was found that the 9ORF1
      protein interacts directly, in vitro and in vivo, with the PDZ domain-containing
      protein hDlg/SAP97 (DLG), which is a mammalian homolog of the Drosophila discs
      large tumor suppressor protein and which also binds the adenomatous polyposis
      coli tumor suppressor protein. Of interest, in forming complexes, the 9ORF1
      protein preferentially associated with the second PDZ domain of DLG, similar to
      adenomatous polyposis coli protein. Human T cell leukemia virus type 1 Tax and
      most oncogenic human papillomavirus E6 oncoproteins also possessed PDZ domain
      binding motifs at their C termini and, significantly, human T cell leukemia virus
      type 1 Tax and human papillomavirus 18 E6 proteins bound DLG in vitro.
      Considering the requirement of the 9ORF1 C-terminal region in transformation,
      these findings suggest that interactions with the cellular factor DLG may
      contribute to the tumorigenic potentials of several different human virus
      oncoproteins.

PMID- 9192624
TI  - In vitro and in vivo characterization of novel mRNA motifs that bind special
      elongation factor SelB.
AB  - The special elongation factor SelB of Escherichia coli promotes selenocysteine
      incorporation into formate dehydrogenases. This is thought to be achieved through
      simultaneous binding to selenocysteyl-tRNASec and, in the case of formate
      dehydrogenase H, to an fdhF mRNA hairpin structure 3' adjacent to the UGA
      selenocysteine codon. By in vitro selection, novel RNA sequences ("aptamers"),
      which can interact tightly and specifically with SelB, were isolated from an RNA
      library. The library was comprised of mutagenized variants of the wild-type fdhF
      mRNA hairpin. One-half of the selected sequences contained the apical stem-loop
      of the fdhF mRNA hairpin highly conserved. Some of the aptamers showed deviations
      in the primary sequence within this region of the wild-type fdhF hairpin motif
      while still binding with high affinity to SelB. Binding studies performed with
      truncated versions of SelB revealed that aptamers binding to different sites on
      the protein have been selected. To dissect SelB binding to the fdhF hairpin from
      the overall biological function of this complex, four selected aptamers were
      analyzed in vivo for UGA readthrough in a lacZ fusion construct. Among these, one
      promoted UGA readthrough in vivo. Three of the aptamers, however, were
      drastically reduced or unable to replace the fdhF mRNA hairpin in vivo, despite
      the similar secondary structure and binding affinities of these RNAs compared
      with the wild-type motif. This finding implies functions of the fdhF hairpin that
      go beyond the mere tethering of selenocysteyl-tRNASec to the UGA codon.

PMID- 9192625
TI  - Pacifastin, a novel 155-kDa heterodimeric proteinase inhibitor containing a
      unique transferrin chain.
AB  - A 155-kDa proteinase inhibitor, pacifastin, from plasma of the freshwater
      crayfish, Pacifastacus leniusculus, was found to be composed of two covalently
      linked subunits. The two subunits are encoded by two different mRNAs, which were
      cloned and sequenced. The heavy chain of pacifastin (105 kDa) is related to
      transferrins, containing three transferrin lobes, two of which seem to be active
      for iron binding. The light chain of pacifastin (44 kDa) is the inhibitory
      subunit, and has nine cysteine-rich inhibitory domains that are homologous to
      each other and to low molecular weight proteinase inhibitors isolated from the
      grasshopper, Locusta migratoria. The nine light chain domains and the Locusta
      inhibitors share a characteristic cysteine array (Cys-Xaa9-12-Cys-Xaa2-Cys-Xaa
      Cys-Xaa6-8-Cys-Xaa4++ +-Cys) distinct from any described proteinase inhibitor
      family, suggesting that they constitute a new family of proteinase inhibitors.
      Pacifastin is the first known protein that has combined properties of a
      transferrin-like molecule and a proteinase inhibitor.

PMID- 9192626
TI  - DNA damage-dependent transcriptional arrest and termination of RNA polymerase II
      elongation complexes in DNA template containing HIV-1 promoter.
AB  - We have developed a new biochemical method to isolate a homogeneous population of
      RNA polymerase II (RNA pol II) elongation complexes arrested at a DNA damage
      site. The method involves triple-helix formation at a predetermined site in DNA
      template with a third strand labeled with psoralen at its 5'-end and a biotin at
      the 3'-end. After triplex formation and near-ultraviolet irradiation (360 nm),
      DNA templates modified with psoralen were immobilized on streptavidin-coated
      magnetic beads and used for in vitro transcription reactions with HeLa nuclear
      extracts. Separation of magnetic beads from solution results in isolation of
      arrested elongation complexes on the immobilized DNA templates. We have applied
      the method to arrest RNA pol II elongation complexes on a DNA template containing
      HIV-1 promoter. Our results indicate that psoralen crosslink in the template
      strand efficiently arrests elongation complexes, and psoralen monoadducts
      terminate transcription. Our results also demonstrate that a triple-helical
      structure stabilized by an intercalator, acridine, attached to the third strand
      of the helix inhibits transcription by a termination pathway. Isolation of stable
      RNA pol II elongation complexes arrested at DNA damage sites is a remarkable
      finding. This result demonstrates that arrested elongation complexes are
      impervious to DNA damage repair machinery and other regulatory proteins present
      in HeLa nuclear extracts. The method of delivering site-specific psoralen damage
      by a triplex structure and isolation of arrested RNA pol II elongation complexes
      should be generalizable to any promoter and DNA template sequences. This strategy
      provides a new approach to study the mechanism of transcription elongation and
      transcription-coupled DNA damage repair.

PMID- 9192627
TI  - Monomeric isomers of human interleukin 5 show that 1:1 receptor recruitment is
      sufficient for function.
AB  - The normally dimeric human interleukin 5 (IL-5) was re-engineered into two
      monomeric isomer forms to investigate mechanistic features of receptor
      recognition. One form, denoted GM1-IL-5, is a CD-loop expanded form, in which an
      8-residue linker designed for flexibility was inserted between residues 85 and
      86. The second, denoted DABC-IL-5, is a circularly permuted form of human IL-5 in
      which a chain discontinuity was introduced in the CD loop and the two consequent
      chain fragments were joined at the normal N and C termini by a di-glycyl linker.
      Both IL-5 isomers folded into stable monomers in solution as shown by
      sedimentation equilibrium and CD and formed an intrachain disulfide bond
      predicted from the structure of wild type IL-5. From titration microcalorimetry
      and optical biosensor analyses, both monomers were shown to interact with the IL
      5 receptor alpha chain with 1:1 stoichiometry and affinities 30- to 40-fold
      weaker than for the dimeric wild type protein. And both monomers stimulated cell
      proliferation of human IL-5 receptor positive cells with a concentration
      dependence close to that of wild type. The data show that both monomeric and
      dimeric forms of IL-5 function through similar 1:1 receptor alpha chain
      recruitment processes and that it is the helical packing of the monomeric four
      helix bundle unit in IL-5, rather than the helical connectivity itself, that
      appears to play the major role in presenting structural epitopes to trigger
      functional receptor activation.

PMID- 9192628
TI  - Mutations in HIV reverse transcriptase which alter RNase H activity and decrease
      strand transfer efficiency are suppressed by HIV nucleocapsid protein.
AB  - Structural studies of authentic HIV reverse transcriptase (RT) suggest a role for
      the p51 carboxyl terminus in forming an active RNase H conformation [Rodgers, D.
      W., Gamblin, S. J., Harris, B. A., Ray, S., Culp, J. S., Hellmig, B., Woolf, D.
      J., Debouck, C. & Harrison, S. C. (1995) Proc. Natl. Acad. Sci. USA 92, 1222
      1226]. We have purified mutant RT heterodimers containing deletion of 5, 9, or 13
      amino acids from the p51 carboxyl terminus. These "selectively deleted"
      heterodimers have been analyzed for changes in RNA-dependent DNA polymerase
      activity, RNase H activity, and the ability to catalyze DNA strand transfer. As
      deletions extended into the p51 subunit, a decrease in the stability of the RT
      DNA complex was apparent. The largest effect was observed for p66/p51Delta13 RT,
      which showed a 3-fold decrease relative to wild-type RT. RNase H activity was
      measured by digestion of the RNA in a 5' 32P-labeled RNA/DNA hybrid. Deletion of
      5 or 9 amino acids from p51 had little effect on synthesis-dependent and
      synthesis-independent RNase H activities. In contrast, deletion of 13 amino acids
      from p51 increased the length of the hydrolysis products of both RNase H
      activities by 8-10 bp, thus changing the spatial relationship between the
      polymerase and RNase H active sites from a distance of 17-18 bp to 26-27 bp. The
      Delta13 derivative was also incapable of efficient DNA strand transfer. This
      defect in strand transfer could be suppressed by the 71-amino acid form of HIV
      nucleocapsid protein (NC) but not by the 55-amino acid form (NC55) or by equine
      infectious anemia virus NC. These results provide evidence for the existence of a
      specific complex between RT and NC and are discussed in terms of the role of this
      complex in proviral DNA synthesis.

PMID- 9192629
TI  - The recombination hotspot Chi is recognized by the translocating RecBCD enzyme as
      the single strand of DNA containing the sequence 5'-GCTGGTGG-3'.
AB  - The RecBCD enzyme of Escherichia coli functions in the seemingly disparate roles
      of homologous recombination and the degradation of DNA. Which of these two roles
      it assumes is regulated by the 8-base recombination hotspot, Chi. Using double
      stranded DNA substrates that are heteroduplex at the Chi locus we have
      established the determinants for Chi recognition. Our results show that an
      actively translocating RecBCD enzyme requires only the sequence information in
      the 5'-GCTGGTGG-3'-containing strand to recognize and to be regulated by Chi.
      Furthermore, the RecBCD enzyme can translocate through DNA heteroduplex bubbles
      as large as 22 bases, and still recognize a Chi sequence embedded in this region.
      This implies that recognition of Chi occurs following the unwinding of the DNA.

PMID- 9192630
TI  - Alterations of the outer membrane composition in Escherichia coli lacking the
      histone-like protein HU.
AB  - Escherichia coli cells lacking the histone-like protein HU form filaments and
      have an abnormal number of anucleate cells. Furthermore, their phenotype
      resembles that of rfa mutants, the well-characterized deep-rough phenotype, as
      they show an enhanced permeability that renders them hypersensitive to
      chloramphenicol, novobiocin, and detergents. We show that, unlike rfa mutants,
      hupAB mutants do not have a truncated lipopolysaccharide but do have an abnormal
      abundance of OmpF porin in their outer membrane. While the complete absence of HU
      does not abolish the osmoregulation of OmpF protein synthesis, the steady-state
      level of micF RNA, the negative regulator of OmpF, decreases in bacteria lacking
      HU, increasing the basal level of this membrane protein. These findings
      demonstrate a novel link between a bacterial chromosomal protein and the outer
      membrane composition.

PMID- 9192631
TI  - Activation of RNA polymerase II by topologically linked DNA-tracking proteins.
AB  - Almost all proteins mediating transcriptional activation from promoter-distal
      sites attach themselves, directly or indirectly, to specific DNA sequence
      elements. Nevertheless, a single instance of activation by a prokaryotic
      topologically linked DNA-tracking protein has also been demonstrated. The scope
      of the latter class of transcriptional activators is broadened in this work.
      Heterologous fusion proteins linking the transcriptional activation domain of
      herpes simplex virus VP16 protein to the sliding clamp protein beta of the
      Escherichia coli DNA polymerase III holoenzyme are shown to function as
      topologically DNA-linked activators of yeast and Drosophila RNA polymerase II.
      The beta:VP16 fusion proteins must be loaded onto DNA by the clamp-loading E.
      coli gamma complex to be transcriptionally active, but they do not occupy fixed
      sites on the DNA. The DNA-loading sites of these activators have all the
      properties of enhancers: they can be inverted and their locations relative to the
      transcriptional start site are freely adjustable.

PMID- 9192632
TI  - The abalone egg vitelline envelope receptor for sperm lysin is a giant
      multivalent molecule.
AB  - Abalone sperm lysin is a 16-kDa acrosomal protein, which nonenzymatically and
      species selectively creates a hole in the egg vitelline envelope (VE) through
      which the sperm passes to reach the egg cell membrane. The crystal structures of
      both monomeric and dimeric lysins have been solved and the sequences of lysins
      from 20 abalone species have been determined. As a first step in understanding
      the molecular mechanism by which lysin creates a hole in the VE, its VE receptor
      was isolated. The VE receptor for lysin (VERL) is an unbranched, rod-like
      molecule with an approximate relative molecular mass of 2 million; half the mass
      being carbohydrate. Fluorescence polarization studies showed positive
      cooperativity in the binding of lysin to VERL (EC50 approximately 9 nM) and were
      consistent with the species selectivity of lysin in dissolving VEs. Each molecule
      of VERL bound between 126 and 142 molecules of monomeric lysin (two independent
      assays), showing that VERL possesses repetitive lysin-binding motifs.

PMID- 9192633
TI  - Similar processes mediate glycopeptide export from the endoplasmic reticulum in
      mammalian cells and Saccharomyces cerevisiae.
AB  - Glycopeptides are transported from the lumen of the yeast endoplasmic reticulum
      (ER) to the cytosol and in contrast to secretory proteins do not enter ER-to
      Golgi transport vesicles. In a cell-free system, this process is ATP- and cytosol
      dependent. While yeast cytosol promotes the export of glycopeptides from
      mammalian ER in vitro, glycopeptide release cannot be detected in the presence of
      mammalian cytosol. We demonstrate that this is due to an N-glycanase activity in
      mammalian cytosol rather than lack of glycopeptide transport activity in
      mammalian microsomes. Monitoring the amount of glycopeptide enclosed in ER
      membranes we show the cytosol- and ATP-dependent release of glycopeptide from
      mammalian microsomes. The fact that glycopeptide export can be achieved with ER
      and cytosol derived from heterologous sources indicates that glycopeptide export
      from the ER is an important process conserved during evolution.

PMID- 9192634
TI  - Estimation of mean exocytic vesicle capacitance in mouse adrenal chromaffin
      cells.
AB  - Whole-cell membrane capacitance measurements are frequently used to monitor
      neuronal and nonneuronal secretory activity. However, unless individual fusion
      events can be resolved, the type of the fusing vesicles cannot be identified in
      these experiments. Here we apply statistical analysis of trial-to-trial
      variations between depolarization-induced capacitance increases of mouse adrenal
      chromaffin cells and obtain estimates for the capacitance contribution of
      individual exocytic vesicles between 0.6 and 2 fF. For comparison, measurements
      of membrane capacitance were combined with amperometric recordings of
      catecholamine release during intracellular perfusion of chromaffin cells with
      high [Ca2+]. Crosscorrelation of both signals yielded a mean capacitance
      contribution of individual catecholaminergic vesicles of 1.3 fF. We suggest that
      depolarization-induced capacitance increases in mouse adrenal chromaffin cells
      mainly represent fusion of chromaffin granules.

PMID- 9192635
TI  - Voltage gating of Escherichia coli porin channels: role of the constriction loop.
AB  - In the homotrimeric OmpF porin from Escherichia coli, each channel is constricted
      by a loop protruding into the beta-barrel of the monomer about halfway through
      the membrane. The water-filled channels exist in open or closed states, depending
      on the transmembrane potential. For the transition between these conformations,
      two fundamentally different mechanisms may be envisaged: a bulk movement of the
      constriction loop L3 or a redistribution of charges in the channel lumen. To
      distinguish between these hypotheses, nine mutant proteins were constructed on
      the basis of the high-resolution x-ray structure of the wild-type protein.
      Functional changes were monitored by measuring single-channel conductance and
      critical voltage of channel closing. Structural alterations were determined by x
      ray analysis to resolutions between 3.1 and 2.1 A. Tethering the tip of L3 to the
      barrel wall by a disulfide bridge (E117C/A333C), mobilizing L3 by perturbing its
      interaction with the barrel wall (D312N, S272A, E296L), or deleting residues at
      the tip of the loop (Delta116-120) did not alter appreciably the sensitivity of
      the channels to an external potential. A physical occlusion, due to a gross
      movement of L3, which would cause the channels to assume a closed conformation,
      can therefore be excluded.

PMID- 9192636
TI  - Identification of a nuclear matrix targeting signal in the leukemia and bone
      related AML/CBF-alpha transcription factors.
AB  - Transcription factors of the AML (core binding factor-alpha/polyoma enhancer
      binding protein 2) class are key transactivators of tissue-specific genes of the
      hematopoietic and bone lineages. Alternative splicing of the AML-1 gene results
      in two major AML variants, AML-1 and AML-1B. We show here that the
      transcriptionally active AML-1B binds to the nuclear matrix, and the inactive AML
      1 does not. The association of AML-1B with the nuclear matrix is independent of
      DNA binding and requires a nuclear matrix targeting signal (NMTS), a 31 amino
      acid segment near the C terminus that is distinct from nuclear localization
      signals. A similar NMTS is present in AML-2 and the bone-related AML-3
      transcription factors. Fusion of the AML-1B NMTS to the heterologous GAL4-(1-147)
      protein directs GAL4 to the nuclear matrix. Thus, the NMTS is necessary and
      sufficient to target the transcriptionally active AML-1B to the nuclear matrix.
      The loss of the C-terminal domain of AML-1B is a frequent consequence of the
      leukemia-related t(8;21) and t(3;21) translocations. Our results suggest this
      loss may be functionally linked to the modified interrelationships between
      nuclear structure and gene expression characteristic of cancer cells.

PMID- 9192637
TI  - Vacuolar H+-ATPase in ocular ciliary epithelium.
AB  - The mechanisms controlling the production of aqueous humor and the regulation of
      intraocular pressure are poorly understood. Here, we provide evidence that a
      vacuolar H+-ATPase (V-ATPase) in the ocular ciliary epithelium is a key component
      of this process. In intracellular pH (pHi) measurements of isolated ciliary
      epithelium performed with 2',7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF),
      the selective V-ATPase inhibitor bafilomycin A1 slowed the recovery of pHi in
      response to acute intracellular acidification, demonstrating the presence of V
      ATPase in the plasma membrane. In isolated rabbit ciliary body preparations
      examined under voltage-clamped conditions, bafilomycin A1 produced a
      concentration-dependent decrease in short-circuit current, and topical
      application of bafilomycin A1 reduced intraocular pressure in rabbits, indicating
      an essential role of the V-ATPase in ciliary epithelial ion transport.
      Immunocytochemistry utilizing antibodies specific for the B1 isoform of the V
      ATPase 56-kDa subunit revealed localization of V-ATPase in both the plasma
      membrane and cytoplasm of the native ciliary epithelium in both rabbit and rat
      eye. The regional and subcellular distribution of V-ATPase in specific regions of
      the ciliary process was altered profoundly by isoproterenol and phorbol esters,
      suggesting that change in the intracellular distribution of the enzyme is a
      mechanism by which drugs, hormones, and neurotransmitters modify aqueous humor
      production.

PMID- 9192638
TI  - Developmental regulation and the role of insulin and insulin receptor in
      metanephrogenesis.
AB  - The insulin family of peptides and their receptors influence cellular growth in
      very early preimplantation embryos. In this study their expression and role in
      renal organogenesis was investigated. By immunofluorescence microscopy and in
      situ hybridization, insulin receptor (IR) expression was seen in the ureteric bud
      branches and early nephron precursors in mouse metanephroi harvested at day 13 of
      gestation. The expression gradually decreased in successive stages of gestation,
      and it was confined mainly to renal tubules in 1-week-old mice. Similar
      developmental regulation of the IR and insulin was observed by reverse
      transcriptase-polymerase chain reaction (RT-PCR) analyses. Addition of insulin
      into the culture medium at low concentrations, ranging from 40 to 400 ng/ml,
      induced trophic changes and increased [3H]thymidine incorporation in the
      embryonic renal explants, and inclusion of IR beta-subunit-specific antisense
      oligodeoxynucleotide caused marked dysmorphogenesis and growth retardation of the
      metanephroi. Specificity of the antisense effect was reflected by
      immunoprecipitation experiments in which translational blockade of the beta
      subunit of the IR was observed. RT-PCR analyses revealed that the alpha subunit
      of the IR was unaffected by the antisense treatment of metanephric explants.
      Concomitantly, de novo synthesis of morphogenetic regulatory extracellular matrix
      proteins, especially the proteoglycans, was decreased. Gel-shift analyses
      indicated a failure in the activation of c-fos promoter region binding protein(s)
      by insulin in the antisense oligodeoxynucleotide-treated explants. These studies
      suggest that insulin and its putative receptor are developmentally regulated in
      the murine embryonic metanephros, and they play a role in renal organogenesis,
      possibly by affecting other modulators of morphogenesis-i.e., extracellular
      matrix proteins and protooncogenes.

PMID- 9192639
TI  - Constitutive activation of a slowly migrating isoform of Stat3 in mycosis
      fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis
      fungoides tumor cell lines.
AB  - Mycosis fungoides (MF) is a low-grade cutaneous T cell lymphoma of unknown
      etiology. In this report, the Jak/Stat (Janus kinase/signal transducer and
      activator of transcription) signaling pathway was investigated in tumor cell
      lines established from skin biopsy specimens from a patient with MF. Jaks link
      cytokine receptors to Stats, and abnormal Jak/Stat signaling has been observed in
      some hemopoietic cancers. In MF tumor cells, a slowly migrating isoform of Stat3,
      Stat3(sm), was found to be constitutively activated, i.e., (i) Stat3(sm) was
      constitutively phosphorylated on tyrosine residues, and tyrosine phosphorylation
      was not enhanced by growth factor stimulation; (ii) band shift assays and
      immunoprecipitations of DNA/Stat complexes showed constitutive DNA-binding
      properties of Stat3(sm); and (iii) Stat3(sm) was constitutively associated with
      Jak3. The abnormal activation of Stat3(sm) was highly specific. Thus, neither the
      fast migrating isoform of Stat3 (Stat3(fm)) nor other Stats (Stat1, Stat2, and
      Stat4 through Stat6) were constitutively activated. The Jak kinase inhibitor,
      tyrphostin AG490, blocked the constitutive activation of Stat3(sm) and inhibited
      spontaneous as well as interleukin 2-induced growth of MF tumor cells. In
      conclusion, we have provided evidence for an abnormal Jak/Stat signaling and
      growth regulation in tumor cells obtained from affected skin of an MF patient.

PMID- 9192640
TI  - Purification and molecular cloning of a secreted, Frizzled-related antagonist of
      Wnt action.
AB  - Frizzled polypeptides are integral membrane proteins that recently were shown to
      function as receptors for Wnt signaling molecules. Here, we report the
      identification of a novel, secreted 36-kDa protein that contains a region
      homologous to a putative Wnt-binding domain of Frizzleds. This protein, called
      Frizzled-related protein (FRP), was first identified as a heparin-binding
      polypeptide that copurified with hepatocyte growth factor/scatter factor in
      conditioned medium from a human embryonic lung fibroblast line. Degenerate
      oligonucleotides, based on the NH2-terminal sequence of the purified protein,
      were used to isolate corresponding cDNA clones. These encoded a 313-amino acid
      polypeptide, containing a cysteine-rich domain of approximately 110 residues that
      was 30-40% identical to the putative ligand-binding domain of Frizzled proteins.
      A 4.4-kb transcript of the FRP gene is present in many organs, both in the adult
      and during embryogenesis, and homologs of the gene are detectable in DNA from
      several vertebrate species. In biosynthetic studies, FRP was secreted but, like
      Wnts, tended to remain associated with cells. When coexpressed with several Wnt
      family members in early Xenopus embryos, FRP antagonized Wnt-dependent
      duplication of the embryonic dorsal axis. These results indicate that FRP may
      function as an inhibitor of Wnt action during development and in the adult.

PMID- 9192641
TI  - In vivo repopulating hematopoietic stem cells are present in the murine yolk sac
      at day 9.0 postcoitus.
AB  - The murine yolk sac, being the first site of embryonic blood cell production, has
      long been theorized to contain the migrating hematopoietic stem cells (HSC) that
      seed the liver and initiate hematopoiesis on day 10.0 postcoitus (pc). However,
      it remains controversial whether yolk sac cells isolated before day 11.0 pc
      possess any long-term repopulating HSC activity upon transplantation into adult
      recipient mice. We hypothesized that failure to demonstrate engraftment of day
      <11.0 yolk sac cells in adult hosts may result from an inability of yolk sac
      cells to home to the active adult hematopoietic sites (spleen and bone marrow).
      In the present studies, we transplanted yolk sac cells into conditioned newborn
      mice in whom the liver, as well as the spleen and bone marrow, concomitantly
      function as a site of blood cell formation. We report that yolk sac cells
      isolated from day 9.0 pc embryos provide long-term multilineage reconstitution
      for at least 11 months in primary conditioned newborn mice and for at least 6
      months in secondary recipients. Donor yolk sac HSC progeny repopulated mature
      peripheral blood, thymus, spleen, and bone marrow lymphoid, myeloid, and
      erythroid compartments. Thus, day 9.0 pc yolk sac HSC can contribute to
      definitive multilineage hematopoiesis in transplanted recipients. Determination
      of HSC activity in the day 9.0 pc murine yolk sac suggests that yolk sac HSC are
      available to seed the liver on day 10.0 pc when definitive hematopoiesis is
      initiated.

PMID- 9192643
TI  - Continuous in vitro propagation of the malaria parasite Plasmodium vivax.
AB  - The difficulty in controlling Plasmodium vivax, the most common cause of human
      malaria, has been complicated by growing drug resistance. We have established a
      method to cycle parasite generations in continuous culture using human blood
      cells. Chesson strain parasites were passaged from owl monkey erythrocytes to
      human reticulocytes in McCoy's 5A medium modified with L-glutamine with 25 mM
      Hepes buffer supplemented with 20% AB+ human serum. Reticulocytes were separated
      by differential centrifugation in homologous plasma from the peripheral blood of
      a hemochromatosis patient. Parasites were grown during each 48-hr cycle in a
      static candle jar environment until the beginning of schizogony, at about 36-40
      hr, when reticulocytes were added and cultures transferred to a shaker for 10-12
      hr. The addition of a concentration of 10% reticulocytes resulted in stabilizing
      parasite densities between 0.28 and 0.57 after cycle 3 and increasing the total
      number of parasites at least 2-fold with each generational cycle. Cultured
      parasites successfully infected an owl monkey. The morphology of cultured
      parasites was typical of P. vivax, with highly ameboid trophozoites evident;
      however, infected erythrocytes were enlarged and distorted on thin film
      preparations. The species identity of cultivated parasites was confirmed by
      analysis of the A and C 18S rRNA genes from genomic DNA and expression of only
      the A gene during erythrocytic asexual growth. The ability to culture P. vivax
      opens new opportunities to develop vaccines, test drugs, and clone parasites for
      genome sequencing.

PMID- 9192642
TI  - A "knockdown" mutation created by cis-element gene targeting reveals the
      dependence of erythroid cell maturation on the level of transcription factor GATA
      1.
AB  - The hematopoietic-restricted transcription factor GATA-1 is required for both
      mammalian erythroid cell and megakaryocyte differentiation. To define the
      mechanisms governing its transcriptional regulation, we replaced upstream
      sequences including a DNase I hypersensitive (HS) region with a neomycin
      resistance cassette by homologous recombination in mouse embryonic stem cells and
      generated mice either harboring this mutation (neoDeltaHS) or lacking the
      selection cassette (DeltaneoDeltaHS). Studies of the consequences of these
      targeted mutations provide novel insights into GATA-1 function in erythroid
      cells. First, the neoDeltaHS mutation leads to a marked impairment in the rate or
      efficiency of erythroid cell maturation due to a modest (4- to 5-fold) decrease
      in GATA-1 expression. Hence, erythroid differentiation is dose-dependent with
      respect to GATA-1. Second, since expression of GATA-1 from the DeltaneoDeltaHS
      allele in erythroid cells is largely restored, transcription interference imposed
      by the introduced cassette must account for the "knockdown" effect of the
      mutation. Finally, despite the potency of the upstream sequences in conferring
      high-level, developmentally appropriate expression of transgenes in mice, other
      cis-regulatory elements within the GATA-1 compensate for its absence in erythroid
      cells. Our work illustrates the usefulness of targeted mutations to create
      knockdown mutations that may uncover important quantitative contributions of gene
      function not revealed by conventional knockouts.

PMID- 9192644
TI  - Defensive production of formic acid (80%) by a carabid beetle (Galerita
      lecontei).
AB  - The carabid beetle Galerita lecontei has a pair of abdominal defensive glands
      that secrete a mixture of formic acid, acetic acid, and lipophilic components
      (long-chain hydrocarbons and esters). Formic acid, at the concentration of 80%,
      is the principal constituent. The beetle ejects the secretion as a spray, which
      it aims accurately toward parts of the body subjected to assault. At full
      capacity, the glands store 4.5 mg of formic acid (3% of body mass), enough for
      upward of six ejections. The beetle reloads the glands at a rate of 126 microg of
      formic acid per day. For the approximately 500 secretory cells of the glands,
      this means an hourly output of 10 ng of formic acid per cell, or about 5% of cell
      volume. Replenishing empty glands to their full formic acid load takes the beetle
      an estimated 37 days. Replenishing the 0.7 mg of formic acid expended in a single
      discharge takes 5.5 days.

PMID- 9192645
TI  - Evolution subverting essentiality: dispensability of the cell attachment Arg-Gly
      Asp motif in multiply passaged foot-and-mouth disease virus.
AB  - Aphthoviruses use a conserved Arg-Gly-Asp triplet for attachment to host cells
      and this motif is believed to be essential for virus viability. Here we report
      that this triplet-which is also a widespread motif involved in cell-to-cell
      adhesion-can become dispensable upon short-term evolution of the virus harboring
      it. Foot-and-mouth disease virus (FMDV), which was multiply passaged in cell
      culture, showed an altered repertoire of antigenic variants resistant to a
      neutralizing monoclonal antibody. The altered repertoire includes variants with
      substitutions at the Arg-Gly-Asp motif. Mutants lacking this sequence replicated
      normally in cell culture and were indistinguishable from the parental virus.
      Studies with individual FMDV clones indicate that amino acid replacements on the
      capsid surface located around the loop harboring the Arg-Gly-Asp triplet may
      mediate in the dispensability of this motif. The results show that FMDV
      quasispecies evolving in a constant biological environment have the capability of
      rendering totally dispensable a receptor recognition motif previously invariant,
      and to ensure an alternative pathway for normal viral replication. Thus,
      variability of highly conserved motifs, even those that viruses have adapted from
      functional cellular motifs, can contribute to phenotypic flexibility of RNA
      viruses in nature.

PMID- 9192646
TI  - Ligand binding was acquired during evolution of nuclear receptors.
AB  - The nuclear receptor (NR) superfamily comprises, in addition to ligand-activated
      transcription factors, members for which no ligand has been identified to date.
      We demonstrate that orphan receptors are randomly distributed in the evolutionary
      tree and that there is no relationship between the position of a given liganded
      receptor in the tree and the chemical nature of its ligand. NRs are specific to
      metazoans, as revealed by a screen of NR-related sequences in early- and non
      metazoan organisms. The analysis of the NR gene duplication pattern during the
      evolution of metazoans shows that the present NR diversity arose from two waves
      of gene duplications. Strikingly, our results suggest that the ancestral NR was
      an orphan receptor that acquired ligand-binding ability during subsequent
      evolution.

PMID- 9192648
TI  - Likelihood-mapping: a simple method to visualize phylogenetic content of a
      sequence alignment.
AB  - We introduce a graphical method, likelihood-mapping, to visualize the
      phylogenetic content of a set of aligned sequences. The method is based on an
      analysis of the maximum likelihoods for the three fully resolved tree topologies
      that can be computed for four sequences. The three likelihoods are represented as
      one point inside an equilateral triangle. The triangle is partitioned in
      different regions. One region represents star-like evolution, three regions
      represent a well-resolved phylogeny, and three regions reflect the situation
      where it is difficult to distinguish between two of the three trees. The location
      of the likelihoods in the triangle defines the mode of sequence evolution. If n
      sequences are analyzed, then the likelihoods for each subset of four sequences
      are mapped onto the triangle. The resulting distribution of points shows whether
      the data are suitable for a phylogenetic reconstruction or not.

PMID- 9192649
TI  - Exon/intron structure of aldehyde dehydrogenase genes supports the "introns-late"
      theory.
AB  - Whether or not nuclear introns predate the divergence of bacteria and eukaryotes
      is the central argument between the proponents of the "introns-early" and
      "introns-late" theories. In this study we compared the goodness-of-fit of each
      theory with a probabilistic model of exon/intron evolution and multiple
      nonallelic genes encoding human aldehyde dehydrogenases (ALDHs). Using a
      reconstructed phylogenetic tree of ALDH genes, we computed the likelihood of
      obtaining the present-day ALDH sequences under the assumptions of each competing
      theory. Although on the grounds of its own assumptions each theory accounted for
      the ALDH data significantly better than its rival, the introns-early model
      required frequent intron slippage, and the estimated slippage rates were too high
      to be consistent with reported correlations between the boundaries of ancient
      protein modules and the ends of ancient exons. Because the molecular mechanisms
      proposed to explain intron slippage are incapable of providing such high rates
      and are incompatible with the observed distribution of introns in higher
      eukaryotes, the ALDH data support the introns-late theory.

PMID- 9192650
TI  - Construction and characterization of a reovirus double temperature-sensitive
      mutant.
AB  - The infectious reovirus RNA system was used to construct a mutant with two
      temperature-sensitive (ts) lesions in genome segments M2 and S2, respectively.
      The double mutant is about 300 times more ts than either of its parents, which
      are about 1,500 and 170 times more ts than their wild-type parent reovirus ST3
      strain Dearing. At 39 degrees C the double mutant is essentially unable to
      multiply. In spite of its striking temperature sensitivity, the double mutant
      elicits the formation of significant amounts of neutralizing antibodies in
      newborn mice. Possible mechanisms responsible for this are discussed, as is the
      significance of this double ts mutant in relation to current searches for safe
      and efficient vaccine strains.

PMID- 9192651
TI  - Selective amplification via biotin- and restriction-mediated enrichment (SABRE),
      a novel selective amplification procedure for detection of differentially
      expressed mRNAs.
AB  - We present a novel subtractive enrichment protocol for the identification of
      differentially expressed mRNA species. This procedure, called SABRE (selective
      amplification via biotin- and restriction-mediated enrichment), uses selective
      streptavidin-biotin affinity and restriction enzyme site reconstitution to enrich
      for cDNA species more abundant in one population than in another. Analysis of
      liver cDNA from a mouse strain expressing the neomycin resistance gene
      demonstrated that this procedure is capable of identifying species present in one
      population but absent from another. Furthermore, experiments to identify genes
      with circadian expression patterns in mouse liver demonstrated that SABRE is
      capable of detecting even modest 2- to 10-fold differences in accumulation of
      moderately rare mRNA species, representing as little as 0.03% of total mRNA.
      These experiments identified the gene encoding coumarin 7-hydroxylase as
      displaying circadian expression in mouse liver.

PMID- 9192652
TI  - Photocarcinogenesis and inhibition of intercellular adhesion molecule 1
      expression in cells of DNA-repair-defective individuals.
AB  - Cells from patients with xeroderma pigmentosum complementation group D (XP-D) and
      most patients with trichothiodystrophy (TTD) are deficient in excision repair of
      ultraviolet (UV) radiation-induced DNA damage. Although in both syndromes this
      defect is based on mutations in the same gene, XPD, only XP-D, not TTD,
      individuals have an increased risk of skin cancer. Since the reduction in DNA
      repair capacity is similar in XP-D and TTD patients, it cannot account for the
      difference in skin cancer risk. The features of XP-D and TTD might therefore be
      attributable to differences in the immune response following UV-irradiation, a
      factor which is presumed to be important for photocarcinogenesis. We have
      measured the capacity of UVB radiation to inhibit expression of the immunological
      key molecule intercellular adhesion molecule 1 (ICAM-1) in cells from three
      healthy individuals in comparison to cells from three XP-D and three TTD
      patients. Cells from XP-D patients, but not from TTD patients, exhibited an
      increased susceptibility to UVB radiation-induced inhibition of ICAM-1
      expression. Transfection of XP-D cells with the wild-type XPD cDNA, but not with
      XPC cDNA, corrected this abnormal phenotype. Thus, the skin cancer risk in DNA
      repair-defective individuals correlated with the susceptibility of their cells to
      UVB radiation-induced inhibition of ICAM-1 expression, rather than with their
      defect in DNA repair. The XPD protein has dual roles: in DNA repair and
      transcription. The transcriptional role might be important for the control of
      expression of immunologically relevant genes and thereby contribute to the skin
      cancer risk of a DNA-repair-deficient individual.

PMID- 9192653
TI  - Impaired fertility in mice deficient for the testicular germ-cell protease PC4.
AB  - PC4 is a member of the proprotein convertase family of serine proteases
      implicated in the processing of a variety of polypeptides including prohormones,
      proneuropeptides, and cell surface proteins. In rodents, PC4 transcripts have
      been detected in spermatocytes and round spermatids exclusively, suggesting a
      reproductive function for this enzyme. In an effort to elucidate this function,
      we have disrupted its locus (Pcsk4) by homologous recombination in embryonic stem
      cells and have produced mice carrying the mutation. In intercrosses of
      heterozygous mutant mice, there was low transmission of the mutant Pcsk4 allele
      to the progeny, resulting in lower than expected incidence of heterozygosity and
      null homozygosity. The in vivo fertility of homozygous mutant males was severely
      impaired in the absence of any evident spermatogenic abnormality. In vitro, the
      fertilizing ability of Pcsk4 null spermatozoa was also found to be significantly
      reduced. Moreover, eggs fertilized by these spermatozoa failed to grow to the
      blastocyst stage. These results suggest that PC4 in the male may be important for
      achieving fertilization and for supporting early embryonic development in mice.

PMID- 9192654
TI  - Removal of polymerase-produced mutant sequences from PCR products.
AB  - Heteroduplex DNA lacking d(GATC) methylation is subject to mismatch-provoked
      double-strand cleavage at d(GATC) sites in a reaction dependent on MutH, MutL,
      MutS, and ATP. We have exploited this reaction to develop a method for removal of
      polymerase-produced mutant sequences that arise during sequence amplification by
      PCR. After denaturation and reannealing, the PCR product pool is subjected to
      MutH, MutL, and MutS mismatch repair proteins under double-strand cleavage
      conditions, followed by isolation of uncleaved product by size selection. Use of
      an Escherichia coli lac forward mutation assay has shown that this procedure
      reduces the incidence of polymerase-induced mutant sequences by an order of
      magnitude. Twenty mutants that originated from three independent PCR
      amplification reactions and survived MutHLS treatment all were found to contain
      an infrequently occurring A.T --> T.A transversion mutation at a unique position
      within the product. By contrast, the majority of mutations in untreated PCR
      products were transitions occurring throughout the amplified region, although
      frameshifts and transversions also were observed. The MutHLS method thus can be
      used to effectively remove the majority of mutant sequences produced by
      polymerase errors during PCR amplification.

PMID- 9192656
TI  - The distribution of genes in the genomes of Gramineae.
AB  - Recent investigations showed that most maize genes are present in compositional
      fractions of nuclear DNA that cover only a 1-2% GC (molar fraction of guanosine
      plus cytosine in DNA) range and represent only 10-20% of the genome. These
      fractions, which correspond to compositional genome compartments that are
      distributed on all chromosomes, were collectively called the "gene space."
      Outside the gene space, the maize genome appears to contain no genes, except for
      some zein genes and for ribosomal genes. Here, we investigated the distribution
      of genes in the genomes of two other Gramineae, rice and barley, and used a new
      set of probes to study further the gene distribution of maize. We found that the
      distribution of genes in these three genomes is basically similar in that all
      genes, except for ribosomal genes and some storage protein genes, were located in
      gene spaces that (i) cover GC ranges of 0.8%, 1.0%, and 1.6% and represent 12%,
      17%, and 24% of the genomes of barley, maize, and rice, respectively; (ii) are
      due to a remarkably uniform base composition in the sequences surrounding the
      genes, which are now known to consist mainly of transposons; (iii) have sizes
      approximately proportional to genome sizes, suggesting that expansion-contraction
      phenomena proceed in parallel in the gene space and in the gene-empty regions of
      the genome; and (iv) only hybridize on the gene spaces (and not on the other DNA
      fractions) of other Gramineae.

PMID- 9192655
TI  - Gene targeting by linear duplex DNA frequently occurs by assimilation of a single
      strand that is subject to preferential mismatch correction.
AB  - To study targeted recombination, a single linear 2-kb fragment of LEU2 DNA was
      liberated from a chromosomal site within the nucleus of Saccharomyces cerevisiae,
      by expression of the site-specific HO endonuclease. Gene targeting was scored by
      gene conversion of a chromosomal leu2 mutant allele by the liberated LEU2
      fragment. This occurred at a frequency of only 2 x 10(-4), despite the fact that
      nearly all cells successfully repaired, by single-strand annealing, the
      chromosome break created by liberating the fragment. The frequency of Leu+
      recombinants was 6- to 25-fold higher in pms1 strains lacking mismatch repair. In
      70% of these cases, the colony was sectored for Leu+/Leu-. Similar results were
      obtained when a 4. 1-kb fragment containing adjacent LEU2 and ADE1 genes was
      liberated, to convert adjacent leu2 and ade1 mutations on the chromosome. These
      results suggest that a linear fragment is not assimilated into the recipient
      chromosome by two crossovers each close to the end of the fragment; rather,
      heteroduplex DNA between the fragment and the chromosome is apparently formed
      over the entire region, by the assimilation of one of the two strands of the
      linear duplex DNA. Moreover, the recovery of Leu+ transformants is frequently
      defeated by the cell's mismatch repair machinery; more than 85% of mismatches in
      heteroduplex DNA are corrected in favor of the resident, unbroken (mutant)
      strand.

PMID- 9192657
TI  - Gene identification and DNA sequence analysis in the GC-poor 20 megabase region
      of human chromosome 21.
AB  - In contrast to the distal half of the long arm of chromosome 21, the proximal
      half of approximately 20 megabases of DNA, including 21q11-21 bands, is low in GC
      content, CpG islands, and identified genes. Despite intensive searches, very few
      genes and cDNAs have been found in this region. Since the 21q11-21 region is
      associated with certain Down syndrome pathologies like mental retardation, the
      identification of relevant genes in this region is important. We used a different
      approach by constructing microdissection libraries specifically for this region
      and isolating unique sequence microclones for detailed molecular analysis. We
      found that this region is enriched with middle and low-copy repetitive sequences,
      and is also heavily methylated. By sequencing and homology analysis, we
      identified a significant number of genes/cDNAs, most of which appear to belong to
      gene families. In addition, we used unique sequence microclones in direct
      screening of cDNA libraries and isolated 12 cDNAs for this region. Thus, although
      the 21q11-21 region is gene poor, it is not completely devoid of genes/cDNAs. The
      presence of high proportions of middle and low-copy repetitive sequences in this
      region may have evolutionary significance in the genome organization and function
      of this region. Since 21q11-21 is heavily methylated, the expression of genes in
      this region may be regulated by a delicate balance of methylation and
      demethylation, and the presence of an additional copy of chromosome 21 may
      seriously disturb this balance and cause specific Down syndrome anomalies
      including mental retardation.

PMID- 9192659
TI  - A critical role for neutralizing-antibody-producing B cells, CD4(+) T cells, and
      interferons in persistent and acute infections of mice with lymphocytic
      choriomeningitis virus: implications for adoptive immunotherapy of virus
      carriers.
AB  - This study demonstrates that neutralizing-antibody-producing B cells, CD4(+) T
      cells, and interferons (IFNs) are of key importance in virus control both in
      adoptive immunotherapy of persistent infection and in the late phase of acute
      infection with the WE strain of lymphocytic choriomeningitis virus (LCMV). We
      report the following results. (i) Clearance of LCMV-WE from C57BL/6 carrier mice
      by adoptive transfer of memory spleen cells requires B cells and CD4(+) T cells
      but not necessarily CD8(+) T cells. (ii) At the doses examined, CD8(+) T cells
      contribute to the initial reduction of viral titers but are alone not sufficient
      to clear the virus because they are exhausted. (iii) In the presence of
      functional IFN-gamma, virus clearance correlates well with the generation of
      neutralizing antibodies in the treated carrier mice. (iv) In the absence of
      receptors for IFN-gamma, virus clearance is not achieved. (v) Adoptive
      immunotherapy of mice persistently infected with a distinct virus isolate, LCMV
      Armstrong, revealed only low levels of neutralizing antibodies; in this case,
      CD8(+) T cells were needed for virus clearance in addition to B and CD4(+) T
      cells. (vi) After low dose infection of C57BL/6 mice with LCMV-WE, virus is
      eliminated below detectable levels by CD8(+) T cells, but long-term (>2 months)
      virus control is usually not achieved in the absence of B cells or CD4(+) T
      cells; reappearance of the virus is paralleled either by exhaustion of virus
      specific cytotoxic T lymphocytes or lethal immunopathology. These findings are of
      importance for adoptive immunotherapy strategies against persistent virus
      infections in humans.

PMID- 9192660
TI  - The three-dimensional structure of an H-2Ld-peptide complex explains the unique
      interaction of Ld with beta-2 microglobulin and peptide.
AB  - Solution at 2.5-A resolution of the three-dimensional structure of H-2Ld with a
      single nine-residue peptide provides a structural basis for understanding its
      unique interaction with beta-2 microglobulin (beta2m) and peptide. Consistent
      with the biological data that show an unusually weak association of Ld with
      beta2m, a novel orientation of the alpha1/alpha2 domains of Ld relative to beta2m
      results in a dearth of productive contacts compared with other class I proteins.
      Characteristics of the Ld antigen-binding cleft determine the unique motif of
      peptides that it binds. Ld has no central anchor residue due to the presence of
      several bulky side chains in its mid-cleft region. Also, its cleft is
      significantly more hydrophobic than that of the other class I molecules for which
      structures are known, resulting in many fewer H-bonds between peptide and cleft
      residues. The choice of Pro as a consensus anchor at peptide position 2 appears
      to be related to the hydrophobicity of the B pocket, and to the unique occurrence
      of Ile (which mirrors Pro in its inability to form H-bonds) at position 63 on the
      edge of this pocket. Thus, the paucity of stabilizing H-bonds combined with poor
      complementarity between peptide postion 2 Pro and the B pocket contribute to the
      weak association between Ld and its peptide antigen. The unique structural
      interactions of Ld with beta2m and peptide could make Ld more suited than other
      classical class I molecules to play a role in alternative pathways of antigen
      presentation.

PMID- 9192661
TI  - Major histocompatibility complex class II-transfected tumor cells present
      endogenous antigen and are potent inducers of tumor-specific immunity.
AB  - We have developed an immunotherapy in which tumor cells transfected with
      syngeneic major histocompatibility complex (MHC) class II genes are cell-based
      vaccines for the treatment of established tumor and metastatic disease. If this
      strategy is to be used clinically, convenient methods for generating class II+
      tumor cells are necessary. Interferon-gamma treatment or transduction of the
      class II transactivator (CIITA) gene induces class II expression but also up
      regulates the class II-associated accessory molecules, invariant chain (Ii) and
      DM. To determine if interferon-gamma treatment and CIITA transduction are
      potential immunotherapies, we assessed the tumorigenicity of sarcoma cells
      expressing combinations of class II, Ii, and DM. Since we hypothesized that class
      II-transfected tumor cells not coexpressing Ii and DM present endogenously
      encoded tumor peptides, we have assessed the transfectants for antigen
      presentation activity to MHC class II-restricted antigen-specific CD4(+) T cells.
      Tumor challenge studies demonstrate that tumor cells expressing class II without
      coexpression of Ii or Ii plus DM are highly immunogenic and preferentially
      present endogenous antigens, while tumors coexpressing class II with Ii or Ii
      plus DM are not effective immunogens. Because tumor rejection correlates with
      expression of class II without coexpression of Ii and DM, the most efficacious
      vaccines will express MHC class II without coexpression of Ii and DM and will
      preferentially present endogenous antigen.

PMID- 9192662
TI  - Selective binding of bacterial toxins to major histocompatibility complex class
      II-expressing cells is controlled by invariant chain and HLA-DM.
AB  - Bacterial superantigens (SAgs) bind to major histocompatibility complex (MHC)
      class II molecules and activate T cells in a Vbeta-restricted fashion. We
      recently identified subsets of HLA-DR1 molecules that show selectivity for SAgs.
      Here, we extend these observations by showing that different cell lineages
      demonstrate distinct SAg-binding specificities although they all express HLA-DR1.
      Indeed, B cells bind staphylococcal enterotoxin A (SEA) and toxic shock syndrome
      toxin 1 (TSST-1) with high affinity while staphylococcal enterotoxin B (SEB)
      binding is barely detectable. In contrast, DR1-transfected HeLa cells show
      efficient binding of SEB, but not of SEA or TSST-1. We investigated the class II
      maturation events required for efficient interaction with SAgs and found that the
      ability of cells to bind and present the toxins can be drastically modulated by
      coexpression of the class II-associated invariant chain (Ii) and HLA-DM. SEA
      binding to DR1 molecules required coexpression of Ii, whereas TSST-1 binding was
      selectively enhanced by DM. Binding of SEB was affected by cell type-specific
      factors other than Ii or DM. The selectivity of SAgs for different MHC class II
      populations was minimally affected by HLA-DR intrinsic polymorphism and could not
      be explained by binding to alternative sites on DR molecules. Our results
      indicate that SAgs are sensitive to structural heterogeneity in class II
      molecules, which is consequent to the differential regulation of expression of
      antigen processing cofactors. Therefore, we speculate that Staphylococcus aureus
      have retained the ability to express numerous SAgs in adaptation to the micro
      heterogeneity displayed by MHC class II molecules and that this may relate to
      their ability to infect different tissues.

PMID- 9192663
TI  - Ly-6C regulates endothelial adhesion and homing of CD8(+) T cells by activating
      integrin-dependent adhesion pathways.
AB  - Ly-6C belongs to the Ly-6 family of glycosyl phosphatidylinositol-anchored
      surface glycoproteins and is expressed on a subset of mature CD8(+) T cells. Ly
      6C ligation can mediate T cell activation and causes interleukin 2 secretion in
      cytolytic T cell clones. We characterize herein a new mAb 1G7.G10 against Ly-6C
      that recognizes an epitope involved in lymphocyte adhesion and in lymphocyte
      homing. Pretreatment of lymph node lymphocytes and of purified CD8(+) T cells
      (but not of lymphocytes depleted of CD8(+) T cells) with 1G7.G10 reduced their in
      vitro binding to lymph node high endothelial venules by 28% and 34%,
      respectively. This effect was bypassed by cross-linking Ly-6C molecules with
      1G7.G10 and a second-step antibody. The in vivo homing of (donor) CD8(+) T
      lymphocytes to lymph nodes was reduced by Ly-6C blocking with 1G7. G10 (whole
      antibody) or with its fragments [F(ab) or F(ab)2] by 20% or by 32% and 48%,
      respectively. Cross-linking of Ly-6C in vitro induced very late antigen-4 and
      lymphocyte function-associated antigen 1-mediated aggregation of CD8(+) T cells,
      suggesting that ligand binding to Ly-6C leads to activation of integrins. This
      activation may facilitate homing of Ly-6C+ CD8(+) T cells in vivo.

PMID- 9192664
TI  - The human cytomegalovirus US6 glycoprotein inhibits transporter associated with
      antigen processing-dependent peptide translocation.
AB  - In its attempt to evade cytotoxic T cell recognition, human cytomegalovirus
      encodes several genes that target MHC class I molecules at different points in
      their assembly pathway. We show here that the human cytomegalovirus US6 gene
      encodes a 22-kDa glycoprotein that binds the transporter-associated with antigen
      processing (TAP)/class I complex and inhibits translocation of peptide from the
      cytosol to the endoplasmic reticulum. Major histocompatibility complex class I
      molecules are therefore unable to load TAP-dependent peptides, resulting in the
      retention of MHC class I molecules in the endoplasmic reticulum, with a
      consequent reduction in class I at the cell surface. Interferon-gamma treatment
      of US6 transfected cells overcomes this inhibition of peptide translocation and
      restores class I at the cell surface to wild type levels. The functional
      consequence of TAP inhibition is that US6 transfected cells are unable to present
      endogenous antigen to cytotoxic T lymphocytes and are therefore resistant to
      cytotoxic T lymphocyte lysis.

PMID- 9192665
TI  - The amino terminus of JAK3 is necessary and sufficient for binding to the common
      gamma chain and confers the ability to transmit interleukin 2-mediated signals.
AB  - JAK3 is a protein tyrosine kinase that specifically associates with the common
      gamma chain (gammac), a shared subunit of receptors for interleukin (IL) 2, 4, 7,
      9, and 15. Patients deficient in either JAK3 or gammac presented with virtually
      identical forms of severe combined immunodeficiency (SCID), underscoring the
      importance of the JAK3-gammac interaction. Despite the key roles of JAK3 and
      gammac in lymphocytic development and function, the molecular basis of this
      interaction remains poorly understood. In this study, we have characterized the
      regions of JAK3 involved in gammac association. By developing a number of
      chimeric JAK3-JAK2 constructs, we show that the binding specificity to gammac can
      be conferred to JAK2 by transferring the N-terminal domains of JAK3. Moreover,
      those JAK3-JAK2 chimeras capable of binding gammac were also capable of
      reconstituting IL-2 signaling as measured by inducible phosphorylation of the
      chimeric JAK3-JAK2 protein, JAK1, the IL-2 receptor beta chain, and signal
      transducer and activator of transcription 5A. Subsequent deletion analyses of
      JAK3 have identified the N-terminal JH7-6 domains as a minimal region sufficient
      for gammac association. Furthermore, expression of the mutant containing only the
      JH7-6 domains effectively competed with full-length JAK3 for binding to gammac.
      We conclude that the JH7-6 domains of JAK3 are necessary and sufficient for
      gammac association. These studies offer clues toward a broader understanding of
      JAK-mediated cytokine signaling and may provide a target for the development of
      novel therapeutic modalities in immunologically mediated diseases.

PMID- 9192666
TI  - Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno
      associated virus.
AB  - We describe a general approach for achieving efficient and cell type-specific
      expression of exogenous genes in photoreceptor cells of the mammalian retina.
      Recombinant adeno-associated virus (rAAV) vectors were used to transfer the
      bacterial lacZ gene or a synthetic green fluorescent protein gene (gfp) to mouse
      or rat retinas after injection into the subretinal space. Using a proximal murine
      rod opsin promoter (+86 to -385) to drive expression, reporter gene product was
      found exclusively in photoreceptors, not in any other retinal cell type or in the
      adjacent retinal pigment epithelium. GFP-expressing photoreceptors typically
      encompassed 10-20% of the total retinal area after a single 2-microl injection.
      Photoreceptors were transduced with nearly 100% efficiency in the region directly
      surrounding the injection site. We estimate approximately 2.5 million
      photoreceptors were transduced as a result of the single subretinal inoculation.
      This level of gene transfer and expression suggests the feasibility of genetic
      therapy for retinal disease. The gfp-containing rAAV stock was substantially free
      of both adenovirus and wild-type AAV, as judged by plaque assay and infectious
      center assay, respectively. Thus, highly purified, helper virus-free rAAV vectors
      can achieve high-frequency tissue-specific transduction of terminally
      differentiated, postmitotic photoreceptor cells.

PMID- 9192667
TI  - Effect of tissue factor deficiency on mouse and tumor development.
AB  - Previous reports suggest that tissue factor (TF) may play an essential role in
      embryonic vascular development and tumor angiogenesis. To further examine this
      relationship, the morphology of fully developed TF-deficient embryos and the
      growth of TF-deficient teratomas and teratocarcinomas were analyzed. In a 129/Sv
      genetic background, TF null embryos do not survive beyond mid-gestation. In
      contrast, 14% of 129/Sv x C57BL/6 TF-deficient embryos escape this early
      mortality and survive to birth. On gross and microscopic inspection, these late
      gestation, TF-deficient embryos appear normal. The growth and vascularity of
      TF(+/+), TF(+/-), and TF(-/-) teratomas and teratocarcinomas are
      indistinguishable. Thus, tumor-derived TF is not required for tumor growth and
      angiogenesis and the combined data do not support an essential role for TF in
      embryonic vascular development.

PMID- 9192668
TI  - RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51
      protein.
AB  - The human RAD51 protein is a homologue of the bacteria RecA and yeast RAD51
      proteins that are involved in homologous recombination and DNA repair. RAD51
      interacts with proteins involved in recombination and also with tumor suppressor
      proteins p53 and breast cancer susceptibility gene 1 (BRCA1). We have used the
      yeast two-hybrid system to clone murine cDNA sequences that encode two RAD51
      associated molecules, RAB22 and RAB163. RAB163 encodes the C-terminal portion of
      mouse BRCA2, the homologue of the second breast cancer susceptibility gene
      protein in humans, demonstrating an in vitro association between RAD51 and BRCA2.
      RAB22 is a novel gene product that also interacts with RAD51 in vitro. To detect
      RAD51 interactions in vivo, we developed a transient nuclear focus assay that was
      used to demonstrate a complete colocalization of RAB22 with RAD51 in large
      nuclear foci.

PMID- 9192669
TI  - Loss of the retinoblastoma protein-related p130 protein in small cell lung
      carcinoma.
AB  - The retinoblastoma gene family consists of the tumor suppressor protein pRB and
      its two relatives p107 and p130. These proteins have been implicated in the
      regulation of cell cycle progression, in part, through inactivation of members of
      the E2F transcription factor family. Overexpression of pRB, p107, or p130 leads
      to growth arrest in the G1 phase of the cell cycle, and this arrest is abolished
      by complex formation with the adenovirus E1A, human papilloma virus E7, or simian
      virus 40 T oncoproteins. Inactivation of pRB by gross structural alterations or
      point mutations in the RB-1 gene has been described in a variety of human tumors,
      including retinoblastomas, osteosarcomas, and small cell lung carcinomas. Despite
      the structural and functional similarity between pRB, p107, and p130, alterations
      in the latter two proteins have not been identified in human tumors. We have
      screened a panel of 17 small cell lung carcinoma cell lines for the presence of
      functional p107 and p130 by evaluating their ability to form complexes with E1A
      in vitro. In the GLC2 small cell lung carcinoma cells no p130 protein was
      detected. The loss of the p130 protein is the result of a single point mutation
      within a splice acceptor sequence in the GLC2 genomic DNA. This mutation
      eliminates exon 2, leading to an in-frame stop codon, and no detectable protein
      is produced. These data are, to our knowledge, the first to describe the loss of
      p130 as a consequence of a genetic alteration, suggesting that not only pRB but
      also the other members of the family may contribute to tumorigenesis, providing a
      rationale for the observation that the DNA tumor viruses selectively target all
      the members of the retinoblastoma protein family.

PMID- 9192670
TI  - Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA
      damage-induced apoptosis.
AB  - Cytochrome C is a mitochondrial protein that induces apoptosis when released into
      the cytosol or when added to cell-free extracts. Here we show that cells that
      overexpress the Bcl-2-related protein Bcl-xL fail to accumulate cytosolic
      cytochrome C or undergo apoptosis in response to genotoxic stress.
      Coimmunoprecipitation studies demonstrate that Bcl-xL associates with cytochrome
      C. Cytochrome C binds directly and specifically to Bcl-xL and not to the
      proapoptotic Bcl-xs protein. The results also demonstrate that Bcl-xs blocks
      binding of cytochrome C to Bcl-xL. Our findings support a role for Bcl-xL in
      protecting cells from apoptosis by inhibiting the availability of cytochrome C in
      the cytosol.

PMID- 9192671
TI  - Dwarfism and age-associated spinal degeneration of heterozygote cmd mice
      defective in aggrecan.
AB  - Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused
      by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in
      cartilage. The homozygotes (-/-) are characterized by cleft palate and short
      limbs, tail, and snout. They die just after birth because of respiratory failure,
      and the heterozygotes (+/-) appear normal at birth. Here we report that the
      heterozygotes show dwarfism and develop spinal misalignment with age. Within 19
      months of age, they exhibit spastic gait caused by misalignment of the cervical
      spine and die because of starvation. Histological examination revealed a high
      incidence of herniation and degeneration of vertebral discs. Electron microscopy
      showed a degeneration of disc chondrocytes in the heterozygotes. These findings
      may facilitate the identification of mutations in humans predisposed to spinal
      degeneration.

PMID- 9192672
TI  - Molecular delineation of the smallest commonly deleted region of chromosome 5 in
      malignant myeloid diseases to 1-1.5 Mb and preparation of a PAC-based physical
      map.
AB  - Loss of a whole chromosome 5 or a deletion of the long arm, del(5q), is a
      recurring abnormality in malignant myeloid diseases. In previous studies, we
      delineated a commonly deleted segment of approximately 4 Mb within band 5q31 that
      was flanked by IL9 on the proximal side and D5S166 on the distal side. We have
      generated a physical map of P1 (PAC), bacterial (BAC), and yeast artificial
      chromosome (YAC) clones of this interval. The contig consists of 108 clones (78
      PACs, 2 BACs, and 28 YACs) to which 125 markers (5 genes, 11 expressed sequence
      tags, 12 polymorphisms, and 97 sequence-tagged sites) have been mapped. Using PAC
      clones for fluorescence in situ hybridization analysis of leukemia cells with a
      del(5q), we have narrowed the commonly deleted segment to 1-1.5 Mb between D5S479
      and D5S500. To search for allele loss, we used 7 microsatellite markers within
      and flanking the commonly deleted segment to examine leukemia cells from 28
      patients with loss of 5q, and 14 patients without cytogenetically detectable loss
      of 5q. In the first group of patients, we detected hemizygous deletions,
      consistent with the cytogenetically visible loss; no homozygous deletions were
      detected. No allele loss was detected in patients without abnormalities of
      chromosome 5, suggesting that allele loss on 5q is the result of visible
      chromosomal abnormalities. The development of a stable PAC contig and the
      identification of the smallest commonly deleted segment will facilitate the
      molecular cloning of a myeloid leukemia suppressor gene on 5q.

PMID- 9192673
TI  - Superoxide and peroxynitrite generation from inducible nitric oxide synthase in
      macrophages.
AB  - Superoxide (O-2) and nitric oxide (NO) act to kill invading microbes in
      phagocytes. In macrophages NO is synthesized by inducible nitric oxide synthase
      (iNOS, NOS 2) from L-arginine (L-Arg) and oxygen; however, O-2 was thought to be
      produced mainly by NADPH oxidase. Electron paramagnetic resonance (EPR) spin
      trapping experiments performed in murine macrophages demonstrate a novel pathway
      of O-2 generation. It was observed that depletion of cytosolic L-Arg triggers O-2
      generation from iNOS. This iNOS-mediated O-2 generation was blocked by the NOS
      inhibitor N-nitro-L-arginine methyl ester or by L-Arg, but not by the
      noninhibitory enantiomer N-nitro-D-arginine methyl ester. In L-Arg-depleted
      macrophages iNOS generates both O-2 and NO that interact to form the potent
      oxidant peroxynitrite (ONOO-), which was detected by luminol luminescence and
      whose formation was blocked by superoxide dismutase, urate, or L-Arg. This iNOS
      derived ONOO- resulted in nitrotyrosine formation, and this was inhibited by iNOS
      blockade. iNOS-mediated O-2 and ONOO- increased the antibacterial activity of
      macrophages. Thus, with reduced L-Arg availability iNOS produces O-2 and ONOO-
      that modulate macrophage function. Due to the existence of L-Arg depletion in
      inflammation, iNOS-mediated O-2 and ONOO- may occur and contribute to
      cytostatic/cytotoxic actions of macrophages.

PMID- 9192674
TI  - Cloning and characterization of the R1 and R2 subunits of ribonucleotide
      reductase from Trypanosoma brucei.
AB  - Ribonucleotide reductase (RNR) catalyzes the rate limiting step in the de novo
      synthesis of deoxyribonucleotides by directly reducing ribonucleotides to the
      corresponding deoxyribonucleotides. To keep balanced pools of
      deoxyribonucleotides, all nonviral RNRs studied so far are allosterically
      regulated. Most eukaryotes contain a class I RNR, which is a heterodimer of two
      nonidentical subunits called proteins R1 and R2. We have isolated cDNAs encoding
      the R1 and R2 proteins from Trypanosoma brucei. The amino acid sequence
      identities with the mouse R1 and R2 subunits are 58% and 63%, respectively.
      Recombinant active trypanosome R1 and R2 proteins were expressed in Escherichia
      coli and purified. The R2 protein contains an iron-tyrosyl free radical center
      verified by EPR spectroscopy and iron analyses. Measurement of cytidine 5'
      diphosphate reduction by the trypanosome RNR in the presence of various
      allosteric effectors showed that the activity is highest with dTTP, dGTP, or dATP
      and considerably lower with ATP. The effect of dGTP is either activating (alone)
      or inhibitory (in the presence of ATP). Filter binding studies indicated that
      there are two classes of allosteric effector binding sites that bind ATP or dATP
      (low-affinity dATP site) and ATP, dATP, dGTP, or dTTP (high-affinity dATP site),
      respectively. Therefore, the structural organization of the allosteric sites is
      very similar to the mammalian RNRs, whereas the allosteric regulation of cytidine
      5'-diphosphate reduction is unique. Hopefully, this difference can be used to
      target the trypanosome RNR for therapeutic purposes.

PMID- 9192675
TI  - Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2.
AB  - PKD1 and PKD2 are two recently identified genes that are responsible for the vast
      majority of autosomal polycystic kidney disease, a common inherited disease that
      causes progressive renal failure. PKD1 encodes polycystin, a large glycoprotein
      that contains several extracellular motifs indicative of a role in cell-cell or
      cell-matrix interactions, and the PKD2 encodes a protein with homology to a
      voltage-activated calcium channel and to PKD1. It is currently unknown how
      mutations of either protein functionally cause autosomal polycystic kidney
      disease. We show that PKD1 and PKD2 interact through their C-terminal cytoplasmic
      tails. This interaction resulted in an up-regulation of PKD1 but not PKD2.
      Furthermore, the cytoplasmic tail of PKD2 but not PKD1 formed homodimers through
      a coiled-coil domain distinct from the region required for interaction with PKD1.
      These interactions suggest that PKD1 and PKD2 may function through a common
      signaling pathway that is necessary for normal tubulogenesis and that PKD1 may
      require the presence of PKD2 for stable expression.

PMID- 9192677
TI  - An intestinal mucin is the target substrate for a baculovirus enhancin.
AB  - An invertebrate intestinal mucin (IIM) was identified from a lepidopterous
      insect, Trichoplusia ni. The IIM is a major protein constituent of the
      peritrophic membrane that facilitates the digestive process, as well as
      protecting invertebrate digestive tracts from microbial infections. The IIM
      demonstrated biochemical characteristics similar to vertebrate mucins, but
      exhibited strong association with the chitin-containing peritrophic membrane
      matrix. We have demonstrated that a baculovirus enhancin, which is encoded and
      carried by specific baculoviruses, has mucin-degrading activity both in vitro and
      in vivo. The in vivo degradation of IIM by enhancin was correlated with the
      enhancement of baculovirus infections in insects. These findings have shown that
      viruses have evolved a novel strategy to overcome intestinal mucinous barriers
      against microorganisms by utilizing a mucin-degrading enzyme.

PMID- 9192676
TI  - Virus dynamics and drug therapy.
AB  - The recent development of potent antiviral drugs not only has raised hopes for
      effective treatment of infections with HIV or the hepatitis B virus, but also has
      led to important quantitative insights into viral dynamics in vivo.
      Interpretation of the experimental data depends upon mathematical models that
      describe the nonlinear interaction between virus and host cell populations. Here
      we discuss the emerging understanding of virus population dynamics, the role of
      the immune system in limiting virus abundance, the dynamics of viral drug
      resistance, and the question of whether virus infection can be eliminated from
      individual patients by drug treatment.

PMID- 9192679
TI  - "Willed action": a functional MRI study of the human prefrontal cortex during a
      sensorimotor task.
AB  - Functional MRI (fMRI) was used to examine human brain activity within the
      dorsolateral prefrontal cortex during a sensorimotor task that had been proposed
      to require selection between several responses, a cognitive concept termed
      "willed action" in a positron emission tomography (PET) study by Frith et al.
      [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R.
      Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which
      the subject chooses to move either of two fingers after a stimulus, by fMRI
      experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired
      from four coronal slices in the prefrontal cortex from nine healthy subjects.
      Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial
      resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with
      the PET results in that we saw similar bilateral activations. The present results
      are compared with our previously published fMRI study of a verbal fluency task,
      which had also been proposed by Frith et al. to elicit a "willed action"
      response. We find a clear separation of activation foci in the left dorsolateral
      prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency
      (Brodmann area 45) tasks. Hence, assigning a particular activated region to
      "willed action" is not supported by the fMRI data when examined closely because
      identical regions are not activated with different modalities. Similar modality
      linked activations can be observed in the original PET study but the greater
      resolution of the fMRI data makes the modality linkages more definite.

PMID- 9192678
TI  - Novel expression mechanism for synaptic potentiation: alignment of presynaptic
      release site and postsynaptic receptor.
AB  - A combination of experimental and modeling approaches was used to study cellular
      molecular mechanisms underlying the expression of short-term potentiation (STP)
      and long-term potentiation (LTP) of glutamatergic synaptic transmission in the
      hippocampal slice. Electrophysiological recordings from dentate granule cells
      revealed that high-frequency stimulation of perforant path afferents induced a
      robust STP and LTP of both (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated
      synaptic responses. However, the decay time constant for STP of the AMPA receptor
      mediated excitatory postsynaptic potential was approximately 6 min, whereas the
      decay time constant for STP of the NMDA receptor-mediated excitatory postsynaptic
      potential was only 1 min. In addition, focal application of agonists during the
      expression of STP revealed that the magnitude of conductance change elicited by
      NMDA application was significantly enhanced, whereas the magnitude of conductance
      change elicited by application of AMPA remained constant. These findings are most
      consistent with a postsynaptic mechanism of STP and LTP. Different putative
      mechanisms were evaluated formally using a computational model that included
      diffusion of glutamate within the synaptic cleft, different kinetic properties of
      AMPA and NMDA receptor/channels, and geometric relations between presynaptic
      release sites and postsynaptic receptor/channels. Simulation results revealed
      that the only hypothesis consistent with experimental data is that STP and LTP
      reflect a relocation of AMPA receptor/channels in the postsynaptic membrane such
      that they become more closely "aligned" with presynaptic release sites. The same
      mechanism cannot account for STP or LTP of NMDA receptor-mediated responses;
      instead, potentiation of the NMDA receptor subtype is most consistent with an
      increase in receptor sensitivity or number.

PMID- 9192680
TI  - Area-specific regulation of gamma-aminobutyric acid type A receptor subtypes by
      thalamic afferents in developing rat neocortex.
AB  - Targeting and innervation of the cerebral cortex by thalamic afferents is a key
      event in the specification of cortical areas. The molecular targets of thalamic
      regulation, however, have remained elusive. We now demonstrate that thalamic
      afferents regulate the expression of gamma-aminobutyric acid type A (GABAA)
      receptors in developing rat neocortex, leading to the area-specific expression of
      receptor subtypes in the primary visual (V1) and somatosensory (S1) areas. Most
      strikingly, the alpha1- and alpha5-GABAA receptors exhibited a reciprocal
      expression pattern, which precisely reflected the distribution of thalamocortical
      afferents at postnatal day 7. Following unilateral lesions at the birth of the
      thalamic nuclei innervating V1 and S1 (lateral geniculate nucleus and ventrobasal
      complex, respectively), profound changes in subunit expression were detected 1
      week later in the deprived cortical territories (layers III-IV of V1 and S1). The
      expression of the alpha1 subunit was strongly down-regulated in these layers to a
      level comparable to that in neighboring areas. Conversely, the alpha5 subunit was
      up-regulated and areal boundaries were no longer discernible in the lesioned
      hemisphere. Changes similar to the alpha5 subunit were also seen for the alpha2
      and alpha3 subunits. These results indicate that the differential expression of
      GABAA receptor subtypes in developing neocortex is dependent on thalamic
      innervation, contributing to the emergence of functionally distinct areas.

PMID- 9192681
TI  - Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse
      brain and other tissues.
AB  - Leptin's effects are mediated by interactions with a receptor that is
      alternatively spliced, resulting in at least five different murine forms: Ob-Ra,
      Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re. A mutation in one splice form, Ob-Rb, results in
      obesity in mice. Northern blots, RNase protection assays, and PCR indicate that
      Ob-Rb is expressed at a relatively high level in hypothalamus and low level in
      several other tissues. Ob-Ra is expressed ubiquitously, whereas Ob-Rc, -Rd, and 
      Re RNAs are only detectable using PCR. In hypothalamus, Ob-Rb is present in the
      arcuate, ventromedial, dorsomedial, and lateral hypothalamic nuclei but is not
      detectable in other brain regions. These nuclei are known to regulate food intake
      and body weight. The level of Ob-Rb in hypothalamus is reduced in mice rendered
      obese by gold thioglucose (GTG), which causes hypothalamic lesions. The obesity
      in GTG-treated mice is likely to be caused by ablation of Ob-Rb-expressing
      neurons, which results in leptin resistance.

PMID- 9192682
TI  - Heat transduction in rat sensory neurons by calcium-dependent activation of a
      cation channel.
AB  - The mechanism of heat transduction in vertebrate sensory neurons was investigated
      in vitro by using cultured dorsal root ganglion neurons from adult rat. In
      response to a physiologically relevant range of stimulus temperatures (23-45
      degrees C), a subpopulation of small dorsal root ganglion neurons are depolarized
      by a cation current (heat-activated current, Iheat) that is antagonized by
      extracellular cesium. Heat-induced single-channel currents in cell-attached
      patches are evoked at a similar range of temperatures. Iheat is a calcium
      dependent current activated indirectly by heat-evoked release of calcium from
      intracellular stores. This suggests that the channel itself is not the transducer
      of thermal energy. Similar to nociceptive heat sensation in vivo, Iheat is
      enhanced by the hyperalgesic agent prostaglandin E2 and only partially adapts
      during prolonged heat stimuli. To our knowledge, these data provide the first
      demonstration that ion channels can mediate heat transduction in mammalian
      sensory neurons and provide evidence that heat causes the channels to open via an
      increase in the intracellular second messenger calcium.

PMID- 9192683
TI  - Extracellular calcium sensed by a novel cation channel in hippocampal neurons.
AB  - Extracellular concentrations of Ca2+ change rapidly and transiently in the brain
      during excitatory synaptic activity. To test whether such changes in Ca2+ can
      play a signaling role we examined the effects of rapidly lowering Ca2+ on the
      excitability of acutely isolated CA1 and cultured hippocampal neurons. Reducing
      Ca2+ excited and depolarized neurons by activating a previously undescribed
      nonselective cation channel. This channel had a single-channel conductance of 36
      pS, and its frequency of opening was inversely proportional to the concentration
      of Ca2+. The inhibition of gating of this channel was sensitive to ionic strength
      but independent of membrane potential. The ability of this channel to sense Ca2+
      provides a novel mechanism whereby neurons can respond to alterations in the
      extracellular concentration of this key signaling ion.

PMID- 9192684
TI  - Neurturin shares receptors and signal transduction pathways with glial cell line
      derived neurotrophic factor in sympathetic neurons.
AB  - Neurturin (NTN) is a neurotrophic factor that shares homology with glial cell
      line-derived neurotrophic factor (GDNF). Recently, a receptor complex has been
      identified for GDNF that includes the Ret tyrosine kinase receptor and a
      glycosylphosphatidylinositol-linked protein termed "GDNFRalpha." However,
      differences in the phenotype of Ret and GDNF knockout animals suggest that Ret
      has at least one additional ligand. In this report, we demonstrate that NTN
      induces Ret phosphorylation in primary cultures of rat superior cervical ganglion
      (SCG) neurons. NTN also caused Ret phosphorylation in fibroblasts that were
      transfected stably with Ret and GDNFRalpha but not in cells expressing Ret alone.
      A glycosylphosphatidylinositol-linked protein also was important for NTN and GDNF
      signaling in SCG neurons; phosphatidylinositol-specific phospholipase C treatment
      of SCG cultures reduced the ability of NTN to phosphorylate Ret and the ability
      of NTN or GDNF to activate the mitogen-activated protein kinase pathway. NTN and
      GDNF also caused sustained activation of Ret and the mitogen-activated protein
      kinase pathway in SCG neurons. Finally, both NTN and GDNF activated the
      phosphatidylinositol 3-kinase pathway in SCG neurons, which may be important for
      the ability of NTN and GDNF to promote neuronal survival. These data indicate
      that NTN is a physiologically relevant ligand for the Ret receptor and suggest
      that NTN may have a critical role in the development of many neuronal
      populations.

PMID- 9192685
TI  - Glutamine synthetase protects against neuronal degeneration in injured retinal
      tissue.
AB  - The neurotransmitter glutamate is neurotoxic when it is accumulated in a massive
      amount in the extracellular fluid. Excessive release of glutamate has been shown
      to be a major cause of neuronal degeneration after central nervous system injury.
      Under normal conditions, accumulation of synaptically released glutamate is
      prevented, at least in part, by a glial uptake system in which the glia-specific
      enzyme glutamine synthetase (GS) plays a key role. We postulated that glial cells
      cannot cope with glutamate neurotoxicity because the level of GS is not high
      enough to catalyze the excessive amounts of glutamate released by damaged
      neurons. We examined whether elevation of GS expression in glial cells protects
      against neuronal degeneration in injured retinal tissue. Analysis of lactate
      dehydrogenase efflux, DNA fragmentation, and histological sections revealed that
      hormonal induction of the endogenous GS gene in retinal glial cells correlates
      with a decline in neuronal degeneration, whereas inhibition of GS activity by
      methionine sulfoximine leads to increased cell death. A supply of purified GS
      enzyme to the culture medium of retinal explants or directly to the embryo in ovo
      causes a dose-dependent decline in the extent of cell death. These results show
      that GS is a potent neuroprotectant and that elevation of GS expression in glial
      cells activates an endogenous mechanism whereby neurons are protected from the
      deleterious effects of excess glutamate in extracellular fluid after trauma or
      ischemia. Our results suggest new approaches to the clinical handling of neuronal
      degeneration.

PMID- 9192686
TI  - Membrane-associated molecules regulate the formation of layer-specific cortical
      circuits.
AB  - The columnar organization of the mammalian neocortex is based on radially
      oriented axon collaterals which precisely link cells from distinct cortical
      layers. During development, these interlaminar connections are specific from
      their initial outgrowth: collaterals form only in the target layers and there are
      no transient axonal collaterals in the nontarget layers. To examine whether
      positional cues within individual cortical layers regulate the laminar
      specificity of collateral formation, explants of cells destined for different
      cortical layers were cultured on membranes prepared from target and nontarget
      layers. Axonal growth and branching were examined on homogeneous membrane
      substrates and on alternating stripes of membranes from different layers. Results
      show that axons branch preferentially on membrane substrates from those layers
      that they would target in vivo. In addition, when cortical axons were given a
      choice to grow on membranes from either their target or their nontarget layer,
      they exhibited a clear preference for the target layers. This indicates that
      membrane-associated cues confined to individual layers regulate the formation of
      collaterals of cortical axons and restrict their growth to their target layers.
      Heat inactivation of membranes from target layers resulted in reduced axonal
      branching. The same manipulation of membranes from nontarget layers increased
      axonal branching for one population of cortical neurons. Taken together, these
      results suggest that membrane-associated molecules confined to individual layers
      induce and prevent the formation of axon collaterals in distinct populations of
      cortical neurons. Thus, the expression of layer-specific cues provides important
      constraints for the remodeling of local circuits during cortical development.

PMID- 9192687
TI  - In vivo activity-dependent plasticity at cortico-striatal connections: evidence
      for physiological long-term potentiation.
AB  - The purpose of the present study was to investigate in vivo the activity
      dependent plasticity of glutamatergic cortico-striatal synapses. Electrical
      stimuli were applied in the facial motor cortex and intracellular recordings were
      performed in the ipsilateral striatal projection field of this cortical area.
      Recorded cells exhibited the typical intrinsic membrane properties of striatal
      output neurons and were identified morphologically as medium spiny type I
      neurons. Subthreshold cortical tetanization produced either short-term
      posttetanic potentiation or short-term depression of cortically-evoked excitatory
      postsynaptic potentials. When coupled with a postsynaptic depolarization leading
      the membrane potential to a suprathreshold level, the tetanus induced long-term
      potentiation (LTP) of cortico-striatal synaptic transmission. Induction of
      striatal LTP was prevented by intracellular injection of a calcium chelator
      suggesting that this synaptic plasticity involves an increase of postsynaptic
      free calcium concentration. Contrasting with previous in vitro studies our
      findings demonstrate that LTP constitutes the normal form of use-dependent
      plasticity at cortico-striatal synapses. Since excitation of striatal neurons
      produces a disinhibition of premotor networks, LTP at excitatory striatal inputs
      should favor the initiation of movements and therefore could be critical for the
      functions of basal ganglia in motor learning.

PMID- 9192688
TI  - Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways
      in a late memory consolidation phase of aversively motivated learning in rats.
AB  - cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been recently
      proposed to participate in both the late phase of long term potentiation in the
      hippocampus and in the late, protein synthesis-dependent phase of memory
      formation. Here we report that a late memory consolidation phase of an inhibitory
      avoidance learning is regulated by an hippocampal cAMP signaling pathway that is
      activated, at least in part, by D1/D5 receptors. Bilateral infusion of SKF 38393
      (7.5 microg/side), a D1/D5 receptor agonist, into the CA1 region of the dorsal
      hippocampus, enhanced retention of a step-down inhibitory avoidance when given 3
      or 6 h, but not immediately (0 h) or 9 h, after training. In contrast, full
      retrograde amnesia was obtained when SCH 23390 (0.5 microg/side), a D1/D5
      receptor antagonist, was infused into the hippocampus 3 or 6 h after training.
      Intrahippocampal infusion of 8Br-cAMP (1.25 microg/side), or forskolin (0.5
      microg/side), an activator of adenylyl cyclase, enhanced memory when given 3 or 6
      h after training. KT5720 (0.5 microg/side), a specific inhibitor of PKA, hindered
      memory consolidation when given immediately or 3 or 6 h posttraining. Rats
      submitted to the avoidance task showed learning-specific increases in hippocampal
      3H-SCH 23390 binding and in the endogenous levels of cAMP 3 and 6 h after
      training. In addition, PKA activity and P-CREB (phosphorylated form of cAMP
      responsive element binding protein) immunoreactivity increased in the hippocampus
      immediately and 3 and 6 h after training. Together, these findings suggest that
      the late phase of memory consolidation of an inhibitory avoidance is modulated
      cAMP/PKA signaling pathways in the hippocampus.

PMID- 9192689
TI  - A 10-amino acid sequence of fibroblast growth factor 2 is sufficient for its
      mitogenic activity on neural progenitor cells.
AB  - During development of the central nervous system, neurons and glia are generated
      from immature neural progenitor cells (NPCs). Basic fibroblast growth factor (FGF
      2) is a mitogen for these cells both in vitro and in vivo. However, it is not
      known whether other members of the FGF family have similar mitogenic effects on
      NPCs. We have found that FGF-4, in addition to FGF-2, is a mitogen for NPCs
      isolated from fetal and adult central nervous systems. Other family members have
      no proliferative effects on these cells. FGFs transduce signals to the cytoplasm
      through a family of transmembrane tyrosine kinase receptors (FGFR-1-4) or their
      isoforms. The high-affinity receptor binding sites are found in two regions of
      the FGF-2 molecule. We have examined the involvement of these sites in mitogenic
      signaling. Synthetic peptides corresponding to sequences in FGF-2 receptor
      binding sites were examined in [3H]thymidine incorporation assays for their
      agonist or antagonist activity. A 10-aa sequence present in the first receptor
      binding domain has been found to act as an antagonist, blocking the mitogenic
      effects of FGF-2. Chemical crosslinking studies using 125I-labeled FGF-2 showed
      specific reduction in binding of radiolabeled FGF-2 to its receptors present on
      the membranes of NPCs. The identification of this sequence will assist in the
      study of pathways involved in signal transduction for mitogenesis in these cells
      and elucidate the role of FGF-2 and FGF-4 during normal development and in the
      pathogenesis of disease.

PMID- 9192690
TI  - 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: a partial
      modulator of AMPA receptor desensitization devoid of neurotoxicity.
AB  - In cerebellar granule neurons of neonatal rats micromolar concentrations of 7
      chloro-3-methyl-3,4-dihydro-2H-1,2, 4-benzothiadiazine S,S-dioxide (IDRA-21) and
      cyclothiazide, two negative modulators of the spontaneous agonist-dependent rapid
      desensitization of alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA)
      gated ion channels, facilitate AMPA receptor function by increasing the content
      of free cytosolic Ca2+ as measured by single-cell fura-2 acetoxymethyl ester
      (Fura-2) Ca2+-dependent fluorescence and intracellular Na+ measured with the
      sodium-binding bezofuran isophthalate acetoxymethyl ester fluorescence indicator.
      IDRA-21 increases intracellular Na+ transient with a threshold (5 microM) that is
      approximately 10 times higher and has an intrinsic activity significantly lower
      than that of cyclothiazide. By virtue of its low intrinsic activity, IDRA-21
      elicits a free cytosolic Ca2+ transient increase that is shorter lasting than
      that elicited by cyclothiazide even when the drug is left in contact with
      cultured granule cells for several minutes. Additionally, while dose dependently,
      5-25 microM cyclothiazide in the presence of AMPA is highly neurotoxic, IDRA-21
      (up to 100 microM) is devoid of neurotoxicity. The neurotoxicity elicited by
      cyclothiazide persists in the presence of dizocilpine (an antagonist of N-methyl
      D-aspartate-selective glutamate receptors) but is blocked by 2,3-dihydroxy-6
      nitrosulfamoylbenzo[f]quinoxaline (a competitive AMPA receptor antagonist) and
      the 1-(aminophenyl)-4-methyl-7, 8-methylendioxy-5H-2,3-benzodiazepine (GYKI
      52466; a noncompetitive AMPA receptor antagonist). Since the doses of IDRA-21
      that enhance cognitive processes in rats and monkeys are several orders of
      magnitude lower than those required to elicit marginal neurotoxicity in cultured
      neurons, it can be surmised that IDRA-21 is a potent cognition-enhancing drug
      virtually devoid of neurotoxic liability because it acts as a partial negative
      allosteric modulator of AMPA receptor desensitization.

PMID- 9192691
TI  - Molecular characterization of the sodium channel subunits expressed in mammalian
      cerebellar Purkinje cells.
AB  - Inactivating and noninactivating Na+ conductances are known to generate,
      respectively, the rising phase and the prolonged plateau phase of cerebellar
      Purkinje cell (PC) action potentials. These conductances have different voltage
      activation levels, suggesting the possibility that two distinct types of ion
      channels are involved. Single Purkinje cell reverse transcription-PCR from guinea
      pig cerebellar slices identified two Na+ channel alpha subunit transcripts, the
      orthologs of RBI (rat brain I) and Nach6/Scn8a. The latter we shall name CerIII.
      In situ hybridization histochemistry in rat brain demonstrated broad CerIII
      expression at high levels in many neuronal groups in the brain and spinal cord,
      with little if any expression in white matter, or nerve tracts. RBII (rat brain
      II), the most commonly studied recombinant Na+ channel alpha subunit is not
      expressed in PCs. As the absence of Scn8a has been correlated with motor endplate
      disease (med), in which transient sodium currents are spared, RBI appears to be
      responsible for the transient sodium current in PC. Conversely, jolting mice with
      a mutated Scn8a message demonstrates PC abnormalities in rapid, simple spike
      generation, linking CerIII to the persistent sodium current.

PMID- 9192692
TI  - Relationships between enzymatic flux capacities and metabolic flux rates:
      nonequilibrium reactions in muscle glycolysis.
AB  - The rules that govern the relationships between enzymatic flux capacities (Vmax)
      and maximum physiological flux rates (v) at enzyme-catalyzed steps in pathways
      are poorly understood. We relate in vitro Vmax values with in vivo flux rates for
      glycogen phosphorylase, hexokinase, and phosphofructokinase, enzymes catalyzing
      nonequilibrium reactions, from a variety of muscle types in fishes, insects,
      birds, and mammals. Flux capacities are in large excess over physiological flux
      rates in low-flux muscles, resulting in low fractional velocities (%Vmax = v/Vmax
      x 100) in vivo. In high-flux muscles, close matches between flux capacities and
      flux rates (resulting in fractional velocities approaching 100% in vivo) are
      observed. These empirical observations are reconciled with current concepts
      concerning enzyme function and regulation. We suggest that in high-flux muscles,
      close matches between enzymatic flux capacities and metabolic flux rates (i.e.,
      the lack of excess capacities) may result from space constraints in the
      sarcoplasm.

PMID- 9192693
TI  - Activation of heteromeric G protein-gated inward rectifier K+ channels
      overexpressed by adenovirus gene transfer inhibits the excitability of
      hippocampal neurons.
AB  - G protein-gated inward rectifier K+ channel subunits 1-4 (GIRK1-4) have been
      cloned from neuronal and atrial tissue and function as heterotetramers. To
      examine the inhibition of neuronal excitation by GIRKs, we overexpressed GIRKs in
      cultured hippocampal neurons from 18 day rat embryos, which normally lack or show
      low amounts of GIRK protein and currents. Adenoviral recombinants containing the
      cDNAs for GIRK1, GIRK2, GIRK4, and the serotonin 1A receptor were constructed.
      Typical GIRK currents could be activated by endogenous GABAB, serotonin 5-HT1A,
      and adenosine A1 receptors in neurons coinfected with GIRK1+2 or GIRK1+4. Under
      current clamp, GIRK activation increased the cell membrane conductance by 1- to 2
      fold, hyperpolarized the cell by 11-14 mV, and inhibited action potential firing
      by increasing the threshold current for firing by 2- to 3-fold. These effects
      were not found in non- and mock-infected neurons, and were similar to the effects
      of muscarinic stimulation of native GIRK currents in atrial myocytes. Two
      inhibitory effects of GIRK activation, hyperpolarization and diminution of
      depolarizing pulses, were simulated from the experimental data. These inhibitory
      effects are physiologically important in the voltage range between the resting
      membrane potential and the potential where voltage-gated Na+ and K+ currents are
      activated; that is where GIRK currents are outward.

PMID- 9192694
TI  - The AP2 domain of APETALA2 defines a large new family of DNA binding proteins in
      Arabidopsis.
AB  - APETALA2 (AP2) plays an important role in the control of Arabidopsis flower and
      seed development and encodes a putative transcription factor that is
      distinguished by a novel DNA binding motif referred to as the AP2 domain. In this
      study we show that the AP2 domain containing or RAP2 (related to AP2) family of
      proteins is encoded by a minimum of 12 genes in Arabidopsis. The RAP2 genes
      encode two classes of proteins, AP2-like and EREBP-like, that are defined by the
      number of AP2 domains in each polypeptide as well as by two sequence motifs
      referred to as the YRG and RAYD elements that are located within each AP2 domain.
      RAP2 genes are differentially expressed in flower, leaf, inflorescence stem, and
      root. Moreover, the expression of at least three RAP2 genes in vegetative tissues
      are controlled by AP2. Thus, unlike other floral homeotic genes, AP2 is active
      during both reproductive and vegetative development.

PMID- 9192695
TI  - Stress proteins on the yeast cell surface determine resistance to osmotin, a
      plant antifungal protein.
AB  - Strains of the yeast Saccharomyces cerevisiae differ in their sensitivities to
      tobacco osmotin, an antifungal protein of the PR-5 family. However, cells
      sensitive to tobacco osmotin showed resistance to osmotin-like proteins purified
      from the plant Atriplex nummularia, indicating a strict specificity between the
      antifungal protein and its target cell. A member of a gene family encoding stress
      proteins induced by heat and nitrogen limitation, collectively called Pir
      proteins, was isolated among the genes that conveyed resistance to tobacco
      osmotin to a susceptible strain. We show that overexpression of Pir proteins
      increased resistance to osmotin, whereas simultaneous deletion of all PIR genes
      in a tolerant strain resulted in sensitivity. Pir proteins have been
      immunolocalized to the cell wall. The enzymatic digestion of the cell wall of
      sensitive and resistant cells rendered spheroplasts equally susceptible to the
      cytotoxic action of tobacco osmotin but not to other osmotin-like proteins,
      indicating that the cell membrane interacts specifically with osmotin and
      facilitates its action. Our results demonstrate that fungal cell wall proteins
      are determinants of resistance to antifungal PR-5 proteins.

PMID- 9192696
TI  - A novel subviral agent associated with a geminivirus: the first report of a DNA
      satellite.
AB  - Numerous plant RNA viruses have associated with them satellite (sat) RNAs that
      have little or no nucleotide sequence similarity to either the viral or host
      genomes but are completely dependent on the helper virus for replication. We
      report here on the discovery of a 682-nt circular DNA satellite associated with
      tomato leaf curl geminivirus (TLCV) infection in northern Australia. This is the
      first demonstration that satellite molecules are not limited to RNA viral
      systems. The DNA satellite (TLCV sat-DNA) is strictly dependent for replication
      on the helper virus replication-associated protein and is encapsidated by TLCV
      coat protein. It has no significant open reading frames, and it shows no
      significant sequence similarity to the 2766-nt helper-virus genome except for two
      short motifs present in separate putative stem-loop structures: TAATATTAC, which
      is universally conserved in all geminiviruses, and AATCGGTGTC, which is identical
      to a putative replication-associated protein binding motif in TLCV. Replication
      of TLCV sat-DNA is also supported by other taxonomically distinct geminiviruses,
      including tomato yellow leaf curl virus, African cassava mosaic virus, and beet
      curly top virus. Therefore, this unique DNA satellite does not appear to strictly
      conform with the requirements that dictate the specificity of interaction of
      geminiviral replication-associated proteins with their cognate origins as
      predicted by the current model of geminivirus replication.

PMID- 9192697
TI  - Expression of a mutant alpha-zein creates the floury2 phenotype in transgenic
      maize.
AB  - The maize floury2 mutation results in the formation of a soft, starchy endosperm
      with a reduced amount of prolamin (zein) proteins and twice the lysine content of
      the wild type. The mutation is semidominant and is associated with small,
      irregularly shaped protein bodies, elevated levels of a 70-kDa chaperone in the
      endoplasmic reticulum, and a novel 24-kDa polypeptide in the zein fraction. The
      24-kDa polypeptide is a precursor of a 22-kDa alpha-zein protein that is not
      properly processed. The defect is due to an alanine-to-valine substitution at the
      C-terminal position of the signal peptide, which causes the protein to be
      anchored to the endoplasmic reticulum. We postulated that the phenotype
      associated with the floury2 mutation is caused by the accumulation of the 24-kDa
      alpha-zein protein. To test this hypothesis, we created transgenic maize plants
      that produce the mutant protein. We found that endosperm in seeds of these plants
      manifests the floury2 phenotype, thereby confirming that the mutant alpha-zein is
      the molecular basis of this mutation.

PMID- 9192698
TI  - Overexpression of an Arabidopsis thaliana high-affinity phosphate transporter
      gene in tobacco cultured cells enhances cell growth under phosphate-limited
      conditions.
AB  - A higher plant homologue to the high-affinity phosphate transporter gene of yeast
      (Saccharomyces cerevisiae) PHO84 was isolated from Arabidopsis thaliana.
      Expression of the Arabidopsis gene PHT1 at high levels in tobacco-cultured cells
      increased the rate of phosphate uptake. The uptake activity attributable to the
      transgene was inhibited by protonophores, suggesting an H+ cotransport mechanism
      of phosphate uptake, and had a Km of 3.1 microM which is within limits
      characteristic of high-affinity transport mechanisms. These results indicate that
      PHT1 encodes a high-affinity phosphate transporter. The transgenic cells
      exhibited increased biomass production when the supply of phosphate was limited,
      establishing gene engineering of phosphate transport as one approach toward
      enhancing plant cell growth.

PMID- 9192700
TI  - The hippocampus and memory for orderly stimulus relations.
AB  - Human declarative memory involves a systematic organization of information that
      supports generalizations and inferences from acquired knowledge. This kind of
      memory depends on the hippocampal region in humans, but the extent to which
      animals also have declarative memory, and whether inferential expression of
      memory depends on the hippocampus in animals, remains a major challenge in
      cognitive neuroscience. To examine these issues, we used a test of transitive
      inference pioneered by Piaget to assess capacities for systematic organization of
      knowledge and logical inference in children. In our adaptation of the test, rats
      were trained on a set of four overlapping odor discrimination problems that could
      be encoded either separately or as a single representation of orderly relations
      among the odor stimuli. Normal rats learned the problems and demonstrated the
      relational memory organization through appropriate transitive inferences about
      items not presented together during training. By contrast, after disconnection of
      the hippocampus from either its cortical or subcortical pathway, rats succeeded
      in acquiring the separate discrimination problems but did not demonstrate
      transitive inference, indicating that they had failed to develop or could not
      inferentially express the orderly organization of the stimulus elements. These
      findings strongly support the view that the hippocampus mediates a general
      declarative memory capacity in animals, as it does in humans.

PMID- 9192701
TI  - Spatial and temporal coherence in perceptual binding.
AB  - Component visual features of objects are registered by distributed patterns of
      activity among neurons comprising multiple pathways and visual areas. How these
      distributed patterns of activity give rise to unified representations of objects
      remains unresolved, although one recent, controversial view posits temporal
      coherence of neural activity as a binding agent. Motivated by the possible role
      of temporal coherence in feature binding, we devised a novel psychophysical task
      that requires the detection of temporal coherence among features comprising
      complex visual images. Results show that human observers can more easily detect
      synchronized patterns of temporal contrast modulation within hybrid visual images
      composed of two components when those components are drawn from the same original
      picture. Evidently, time-varying changes within spatially coherent features
      produce more salient neural signals.

PMID- 9192703
TI  - The effect of cadmium on the immune behaviour of guinea pigs with experimental
      ascariasis.
AB  - The subchronic effect of cadmium on selected immunological parameters was studied
      in guinea pigs with experimental ascariasis. Cadmium chloride given orally for 28
      days caused a considerable suppression of T- and B-cells in the lymphoid organs
      of intoxicated animals, of the metabolic activity of their peritoneal macrophages
      and a moderate decline in the level of complement CH50 and AH50 from day 1 to day
      28 of the experiment, in comparison with the initial value. After a subsequent
      infection of the subchronically intoxicated guinea pigs the values for both the
      cell populations and the macrophage metabolic activity remained considerably
      suppressed, compared with infected control animals. The phagocytic and metabolic
      activity of macrophages as well as the CH50 and AH50 level, however, increased
      conspicuously for a short time after application of heavy metal and after
      infection but it did not reach the level of the infected group. The level of
      specific circulating antibodies was not affected by intoxication. Compared with
      the controls, the mean intensity of infection with Ascaris larvae migrating in
      the lungs of intoxicated animals increased by 20%. The results have established
      the negative effect of cadmium on the immunological parameters of the cellular
      immunity and humoral immunity studied and the impairment of the organism's
      response to the antigenic stimulus after an A. suum infection.

PMID- 9192704
TI  - Proteoglycans from adult worms of Schistosoma haematobium.
AB  - Different types of proteoglycans (PGs) from adult worms of Schistosoma
      haematobium, were sequentially extracted using chaotropic agents under
      associative conditions (0.5 M GnCl), dissociative conditions (4 M GnCl) and
      detergents (Triton X-100 and SDS). The extracts were designated F1, F2, F3 and
      F4, respectively. The highest amount of uronic acid and carbohydrate was detected
      in the associative extract (F1) while the highest amount of protein was detected
      in the SDS extract (F4). Agarose polyacrylamide gel electrophoresis (A-PAGE)
      indicated the presence of a different PG in each extract with different
      electrophoretic mobilities. Agarose gel electrophoresis of glycosaminoglycan
      (GAG) separated from GnCl, associative and dissociative extracts, and the residue
      suggested the presence of dermatan sulphate in the two extracts and the residue,
      in addition to a GAG-like material found in the associative extract only. This
      glycosaminoglycan showed resistance to digestion with all mucopolysaccharidases
      and nitrous acid treatment. Gel filtration chromatography of associative extract
      on Sepharose CL-6B indicated the presence of three main uronic acid peaks (P1, P2
      and P3). Chondroitin sulphate was the main GAG that could be detected in peak one
      (P1). Peak two (P2) contains carbohydrate and uronic acid but has no protein or
      absorbance at 280 nm. P2 has two types of GAGs: dermatan sulphate and a GAG-like
      material. The role of this PG in helping the adult schistosomes in evading
      immobilization by the host blood clotting cascade is discussed. Antibodies to
      peak one and peak two were detected in hamster sera infected with S. haematobium
      and S. mansoni using the ELISA test. The specificity of peak two was found to be
      evident in its low cross-reactivity (18.9%) when confronted with S. mansoni
      infected sera.

PMID- 9192709
TI  - Helminth detoxification mechanisms.

PMID- 9192707
TI  - Comparison of human and murine isolates of Schistosoma mansoni from Richard-Toll,
      Senegal, by isoelectric focusing.
AB  - Studies on human and murine isolates of Schistosoma mansoni, from Richard-Toll,
      Senegal, were carried out by isoelectric focusing in polyacrylamide gels. Seven
      enzyme systems; lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glucose
      6-phosphate dehydrogenase (G6PD), acid phosphatase (AcP), hexokinase (HK),
      glucose phosphate isomerase (GPI), and phosphoglucomutase (PGM), were used to
      compare the two isolates. All systems tested, apart from LDH, were found to be
      polymorphic for both isolates. Interestingly, one phenotype is more frequent than
      the remainder. The results show that there is no significant genetic variation
      between the S. mansoni isolates from man and the rodents, Arvicanthis niloticus
      and Mastomys huberti.

PMID- 9192710
TI  - Detection of gastrointestinal helminth infections using coproantigen and
      molecular diagnostic approaches.

PMID- 9192711
TI  - Schistosomiasis in the Senegal River Basin: before and after the construction of
      the dams at Diama, Senegal and Manantali, Mali and future prospects.
AB  - Ecological changes in the Senegal River Basin (SRB) resulting from the
      construction of a barrage at Diama, Senegal on the Senegal River to prevent the
      intrusion of sea water into the river, and a dam at Manantali, Mali on the Bafing
      River to control the flow of water and to generate electricity, have been
      responsible for changes in the epidemiology of human schistosomiasis. The
      introduction of Schistosoma mansoni into the Lower and Middle Valleys of the SRB
      and subsequent spread of the parasite in the human population is recorded with
      regard to prevalence and intensity. New foci of S. haematobium are described. The
      reduction in salinity and change from an acidic to an alkaline environment in the
      water are beneficial to both the fecundity and growth of freshwater snails and
      transmission of the parasite. The creation of new irrigation canals and expansion
      of the rice fields have provided new habitats for intermediate hosts to colonize.
      The evidence for praziquantel resistance/tolerance by populations of S. mansoni
      and the possibilities of the development, production and testing of a vaccine
      against human schistosomiasis are discussed. Future studies will monitor the
      spread of human urinary and mesenteric schistosomiasis in the SRB, will evaluate
      further the presence of praziquantel resistance/tolerance in S. mansoni, will
      examine the heavily infected human population for pathological symptoms and
      determine the most appropriate methods to control this severe outbreak of human
      schistosomiasis.

PMID- 9192712
TI  - The effect of dexamethasone on resistance of older lambs to infection with
      Nematodirus battus.
AB  - Old lambs (8 months of age) infected with 50,000 L3 of Nematodirus battus had
      larvae developing normally in their tissues on day 4 post-infection (P.I.), but
      by day 8 P.I. there were only 4105 +/- 1044 worms left in the alimentary tract.
      Some of these worms contained crystals in their intestine. Eight-month-old lambs
      treated with dexamethasone and infected with 50,000 L3 of N. battus contained a
      mean worm burden of 7878 +/- 1262 on 18 days P.I. Untreated 8-month-old lambs
      similarly infected were virtually worm free by day 18 P.I. Peripheral
      eosinophilia became elevated in the untreated lambs over the course of infection
      and, at post-mortem, the tissue mast cell and eosinophil counts were much higher
      than in the dexamethasone treated group. Although the phenomenon of age
      resistance is thought to have a strong immunological component, there may also be
      other physiological factors, resulting in fewer nematodes and lower fecundity of
      the worms.

PMID- 9192713
TI  - In vitro effects of Trichinella spiralis on muscle cells.
AB  - Introduction of excretory/secretory (ES) products of both infective-stage and
      newborn larvae of Trichinella spiralis into cultures of primary rat myocytes
      elicited morphological and structural changes in the myotubes. They appeared more
      granular, thinner, and failed to form networks. The most prominent lesion was the
      formation of 'nodular' structures, each bearing an enlarged nucleus, along the
      myotubes. Each node contained numerous cavities enclosed by an intact sarcolemma.
      Co-culture of myocytes with newborn larvae also elicited nodular formation but
      each node contained a large central cavity encircled by smaller ones. An
      immunocytolocalization study using IFAT and laser confocal microscopy showed the
      presence of parasitic epitopes inside the nodes. However, ES products from adult
      worms did not affect the myotubes.

PMID- 9192714
TI  - Immunization of mice against Trichinella spiralis and T. britovi using excretory
      and secretory antigens.
AB  - Immune responses to immunization and infection with Trichinella spiralis and T.
      britovi were studied in NIH high-responder mice. Overall it was shown that T.
      britovi was the more immunogenic, immunization and challenge with this species
      giving greater host-protective immunity. This greater immunogenicity was
      reflected in higher proliferative responses when mesenteric node lymphocytes
      (MLNC) from immunized mice were restimulated with T. britovi antigens in vitro
      and in higher levels of T helper 2 (Th2) lymphocyte-dependent specific IgG1
      antibody responses against this species. MLNC from mice immunized against T.
      britovi released more IL-5 when restimulated in vitro, again suggesting a greater
      T helper 2 subset response, but after infection the highest levels of IL-5 were
      recorded from MLNC taken from T. spiralis challenged mice. These data are
      discussed in relation to current understanding of immunological differences
      between species and isolates of the genus Trichinella.

PMID- 9192715
TI  - Patterns of epidemiology and control of onchocerciasis in west Africa.

PMID- 9192717
TI  - How proteins are transported from cytoplasm to the nucleus.
AB  - Nuclear proteins are transported actively through nuclear pores by a selective,
      mediated process. The process is mediated by a nuclear localization signal (NLS),
      and can be divided into at least two steps, (a) targeting to the pores and (b)
      translocation through the pores. The first step involves the formation of a
      stable complex containing a nuclear protein, termed nuclear pore-targeting
      complex (PTAC), in the cytoplasm. The second step, translocation, requires at
      least two soluble factors, a small GTPase Ran and its interacting protein
      p10/nuclear transport factor 2 (NTF2), along with nuclear pore complex
      components. These findings have been generally obtained by using the NLS of SV40
      large T-antigen, and data concerning the detailed mechanism are now accumulating.
      Transport pathways other than for the SV40 T-antigen, for example, extracellular
      signal-dependent nuclear protein import pathway, have also recently been studied.
      Considering all these observations, one should be able to attain an understanding
      of the mechanism of intracellular information transduction between cytoplasm and
      the nucleus.

PMID- 9192718
TI  - Fluorescence spectrometry in studies of carbohydrate-protein interactions.
AB  - Fluorometric spectroscopy is a powerful tool for investigating the interaction
      between a carbohydrate ligand and binding proteins. The measurement is done in
      situ and thus circumventing the need for separation of bound ligand from the free
      ligand. The source of the fluorophore can be intrinsic, i.e., the tryptophan in
      the protein, or extrinsic (contained in the ligand). Techniques for assessing the
      affinity used are measurement on fluorescence intensity change, lifetime,
      polarization anisotropy, and energy transfer. The last technique can also be used
      to study conformational structures of glycopeptides. It is also useful in
      designing substrates for endo-type enzymes which allow continuous monitoring of
      the reaction.

PMID- 9192719
TI  - Crystallization and preliminary X-ray crystallographic study of Streptomyces
      olivaceoviridis E-86 beta-xylanase.
AB  - beta-Xylanase from Streptomyces olivaceoviridis E-86 has been crystallized by the
      hanging drop vapor diffusion method from 25% saturated ammonium sulfate and 2%
      McIlvaine buffer, pH 5.7. The crystals diffract to at least 1.9 A resolution, and
      belong to space group P2(1)2(1)2(1), with unit-cell dimensions of a=79.6 A,
      b=95.2 A, and c=140.3 A. There are probably two xylanase molecules (MW=45 K) per
      asymmetric unit.

PMID- 9192720
TI  - Crystallization and preliminary X-ray diffraction studies of methyl-coenzyme M
      reductase from methanobacterium thermoautotrophicum.
AB  - Methyl-coenzyme M reductase isoenzyme I from the methanogenic Archaeon,
      Methanobacterium thermoautotrophicum (strain Marburg), was crystallized by vapor
      diffusion methods. Crystal form M obtained with 2-methyl-2,4-pentanediol as the
      precipitant displayed space group P2(1), with unit cell parameters of a=83.2 A,
      b=117.4 A, c=125.1 A, and beta= 92.6 degrees, and diffracted at better than 2.8 A
      resolution. Crystal form P grown from polyethylene glycol 400 belonged to space
      group P2(1), and had unit cell parameters of a=83.1 A, b=120.2 A, c=123.1 A, and
      beta=91.7 degrees, diffracting at least to 1.7 A resolution. Both crystal forms
      have one molecule per asymmetric unit and are suitable for X-ray structure
      analysis.

PMID- 9192721
TI  - An engineered bivalent single-chain antibody fragment that increases antigen
      binding activity.
AB  - Bivalent single chain Fv (scFv) was constructed by fusing a polypeptide extension
      containing one or two cysteines to the COOH-terminus of an scFv antibody
      fragment. The scFv protein was expressed and secreted in a recombinant Pichia
      pastoris system as a dimer with a C-terminal disulfide bridge, as determined by
      Western blot analysis under non-reducing conditions. We found that the scFv
      construct with one cysteine in the C-extension (scFv-1Cys) exhibited a much
      higher dimer/monomer ratio than the two cysteine counterpart (scFv-2Cys). Binding
      activity measurements performed by means of a competitive radioimmunoassay showed
      that scFv-1Cys exhibited specific antigen binding activity, which was almost the
      same as that of the parental MAb, and approximately four- and fortyfold higher
      than those of the control scFv monomer and scFv-2Cys.

PMID- 9192722
TI  - Subunit association and monomer structure of CINC/Gro revealed by 1H-NMR.
AB  - Rat CINC/Gro is a 72 residue chemotactic factor of neutrophils, and a member of
      the CXC chemokine family, that includes IL-8 and MGSA/GRO. Although the three
      dimensional structure of CINC/Gro had previously been determined to be that of a
      dimer with 200 mM NaCl, it was shown on both ultracentrifugation analysis and 1H
      NMR spectral analysis that CINC/Gro exists mainly as a monomer at a physiological
      concentration, similar to other proteins belonging to this family. By reducing
      the NaCl concentration, the equilibrium could be shifted to the monomer, making
      it possible to observe the monomer and dimer resonances in 1H-NMR spectra. There
      were no significant chemical shift changes of alpha protons in the beta sheet
      between the monomer and dimer, suggesting that the beta sheet structure was
      retained in the monomer. Instead, the chemical shift changes of a protons were
      significant at I18 and K21, which are located in the long loop region interacting
      with the alpha helix, and V59 at the beginning of the a helix, indicating
      structural changes in the relative positions of the alpha helix and beta sheet.

PMID- 9192723
TI  - Purification and characterization of glutaredoxin (thioltransferase) from rice
      (Oryza sativa L.).
AB  - We purified and characterized glutaredoxin (thioltransferase), which catalyzes
      thiol/disulfide exchange reaction, for the first time in plants. The purification
      procedure employed an immunoabsorbent, antiglutaredoxin-Sepharose. Glutaredoxin
      was purified about 2,200-fold from rice bran and it appeared to be homogeneous on
      SDS-PAGE. MALDI-TOF mass spectrometry revealed that the protein has a molecular
      mass of 11,097.9 Da. Rice glutaredoxin consists of 105 amino acid residues,
      containing the tetrapeptide -Cys-Phe-Pro (Tyr)-Cys-, which constitutes the active
      site of Escherichia coli and mammalian glutaredoxins. Inactivation assay also
      indicated that cysteine residues are responsible for enzyme activity. Kinetic
      analyses revealed that the enzyme did not exhibit normal Michaelis-Menten
      kinetics. The enzyme has an optimum pH of about 8.7 with 2-hydroxyethyl disulfide
      as a substrate. In addition, rice glutaredoxin has dehydroascorbate reductase
      activity, like mammalian glutaredoxin.

PMID- 9192725
TI  - Expression of the long arm sequence of mouse laminin alpha1, beta1, or gamma1
      chain in COS1 cells and assembly of monkey-mouse hybrid laminin.
AB  - Mouse laminin alpha1, beta1, or gamma1 sequence covering truncated regions of the
      long arm was transiently expressed in monkey COS1 cells. Unlike natural laminins,
      in which only alpha beta gamma trimers are selectively assembled and disulfide
      bonded at the long arm, a large fraction of mouse chains formed disulfide-bonded
      homopolymers. However, a small fraction of mouse beta1 (or gamma1) formed hybrid
      beta1gamma1 dimers with endogenous monkey gamma1 (or beta1). These hybrid
      beta1gamma1 dimers formed alpha1 beta1 gamma1 trimer with monkey alpha1. Mouse
      alpha1 also formed disulfide bonds with monkey beta1gamma1 dimer. Thus, a common
      mechanism is shared by laminin chains of different animal origins. Sequences in
      the E8 region at the C-terminal end of the long arm were crucial for this chain
      selective assembly. When the C-terminal sequence of mouse beta1 long arm was
      extended beyond the alpha-loop, the hybrid trimer formation was diminished. This
      supported the model of altered chain arrangement around the alpha-loop.

PMID- 9192724
TI  - Role of histidine 46 in the hydrolysis and the reverse transphosphorylation
      reaction of RNase Rh from Rhizopus niveus.
AB  - In order to study the reaction mechanism of RNase Rh from Rhizopus niveus, the
      rates of cleavage of four 2',3'-cyclic nucleotides by mutant enzymes of RNase Rh,
      H46F, H109F, E105Q, and K108L were measured. H46F is virtually inactive towards
      cyclic nucleotides, but H109F hydrolyzed these substrates at 0.7-4.5% of the
      rates of the native RNase Rh. The other mutants hydrolyzed 2',3'-cyclic
      nucleotides at 15-20% of the rates of the native enzyme. Relative enzymatic
      activities towards four cyclic nucleotides of H109F in the hydrolysis reaction
      (2nd step) were much higher than in the transphosphorylation reaction (the 1st
      step). In the presence of a 13-fold excess of uridine, H109F catalyzed the
      transphosphorylation reaction of 2',3'-cyclic AMP (A>p) to ApU. However, this
      reaction was not catalyzed by H46F mutant or native RNase Rh. These results
      showed that His46 is crucial to the hydrolysis reaction, and to the reversed
      reaction of the transphosphorylation reaction. We suggest that His46 in RNase Rh
      plays a major role in these reactions by acting as a base catalyst to activate
      water and the 5'-hydroxyl group of nucleosides, respectively.

PMID- 9192726
TI  - Involvement of intracellular cyclic GMP and cyclic GMP-dependent protein kinase
      in alpha-elastin-induced macrophage chemotaxis.
AB  - alpha-Elastin with an average molecular mass of 70 kDa, an oxalic acid
      fragmentation product of highly purified insoluble elastin, induced the migration
      of macrophages, with maximum activity at 10(-1) microg/ml. Relative to the
      positive control of 10(-8) M N-formylmethionyl-leucyl-phenylalanine (fMLP), the
      responsiveness of macrophages to alpha-elastin was nearly the same. Checkerboard
      analysis demonstrated that the cell movement is chemotaxis and not chemokinesis.
      A homologous deactivation test showed the possibility of the existence of alpha
      elastin-recognizing sites on macrophages. In connection with macrophage
      chemotaxis in response to alpha-elastin, the intracellular signaling pathway was
      examined. The guanosine 3', 5'-cyclic monophosphate (cGMP) level was enhanced in
      macrophages stimulated by alpha-elastin, whereas the adenosine 3',5'-cyclic
      monophosphate (cAMP) level was not. Chemotaxis assaying of macrophages treated
      with 8-Br cGMP- and dibutyryl cAMP-loaded macrophages indicated that cGMP
      promotes cell movement and cAMP suppresses cell locomotion. The possible
      involvement of protein kinases in the alpha-elastin signaling pathway was
      explored by use of inhibitors specific for cGMP-dependent protein kinase (PKG),
      cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and tyrosine kinase.
      The macrophage chemotactic response to alpha-elastin was inhibited by the PKG
      inhibitor, but not by the PKA, PKC, or tyrosine kinase inhibitor. These results
      suggested that the increase in the cGMP level and the activation of PKG in
      macrophages are involved in alpha-elastin induced macrophage chemotaxis.

PMID- 9192727
TI  - Isolation and molecular cloning of epidermal- and hair follicle-specific
      peptidylarginine deiminase (type III) from rat.
AB  - Peptidylarginine deiminase (PAD) is a post-translational modification enzyme that
      catalyzes deimination of arginine residues of proteins in the presence of calcium
      ions. There are three types of PAD in rodent tissues: PAD types I, II, and III
      [Terakawa et al. (1991) J. Biochem. 110, 661-666]. Type III enzyme was detected
      only in the epidermis and in hair follicles. In this study, we have purified PAD
      type III from 2-day-old rat epidermis by a four-step procedure that included
      soybean trypsin inhibitor-affinity chromatography. The enzyme was purified about
      600-fold from the crude extract and the recovery was 23%. The final preparation
      of the enzyme gave only a single protein band on SDS-PAGE and showed an apparent
      molecular weight of 76,000. Subsequently, we cloned and sequenced the full-length
      cDNA encoding rat PAD type III by reverse transcription-polymerase chain reaction
      (RT-PCR) using degenerate oligonucleotide primers designed from the internal
      amino acid sequences and by the rapid amplification of the cDNA ends method. The
      composite cDNA sequence contained a 5' untranslated region of 42 bp, an open
      reading frame of 1,995 bases that encoded 664 amino acids (Mr=75,036), a 3'
      untranslated region of 1,063 bp, and part of a poly(A)+ tail. The entire reading
      frame sequence of rat PAD type III showed 51% homology with that of rat PAD type
      II, and the C-terminal region is highly conserved between the two types. The
      cloned gene was expressed in Escherichia coli cells to produce PAD type III,
      which had not only enzymatic activity, but also immunoreactivity against specific
      antibodies toward PAD type II. Furthermore, the specific expression of the enzyme
      in the epidermis and hair follicles was confirmed by RT-PCR assays of mRNAs from
      several tissues.

PMID- 9192728
TI  - Functional expression and site-directed mutagenesis of photoactive yellow
      protein.
AB  - The gene encoding photoactive yellow protein (PYP) was isolated from
      Ectothiorhodospira halophila, and a high-level expression system for PYP was
      constructed in Escherichia coli. The molecular weight and the absorption spectrum
      of PYP expressed in E. coli were identical with those of the native PYP isolated
      from E. halophila. The amino acid residues which might interact with the
      chromophore (Tyr42, Glu46, Thr50, Arg52, and Cys69) were mutated by site-directed
      mutagenesis and the absorption spectra of these mutants were examined to study
      the chromophore/protein interaction in PYP. The former three substitutions (Y42F,
      E46Q, and T50V) brought about red-shifts of the absorption spectra, but the
      substitution of Arg52 (R52Q) brought about no change and that of Cys69 (C69S) led
      to no formation of pigments. These results suggest that Tyr42, Glu46, and Thr50
      strongly interact with the chromophore, while Arg52 does not contribute the color
      tuning of PYP.

PMID- 9192730
TI  - HSDJ, a human homolog of DnaJ, is farnesylated and is involved in protein import
      into mitochondria.
AB  - The role of HSDJ, a human homolog of bacterial DnaJ and yeast YDJ1p/MAS5, in
      mitochondrial protein import was examined. Recombinant HSDJ was purified and an
      antibody was prepared. HSDJ mRNA was heat-induced in cultured cells. In pulse
      labeling and chase experiments using COS-7 cells, the endogenous HSDJ homolog was
      prenylated. Transiently expressed HSDJ was also prenylated, whereas its mutant
      C394S in which cysteine of the "CaaX box" was mutated to serine, was not. HSDJ,
      but not C394S, synthesized in rabbit reticulocyte lysate was farnesylated. The
      HSDJ antibody inhibited import of ornithine transcarbamylase precursor (pOTC)
      into isolated mitochondria when added prior to pOTC synthesis, but not when added
      prior to import assay. In transient expression of pOTC in COS-7 cells, pOTC was
      synthesized and processed to the mature form with an apparent half-life of 2-3
      min. Coexpression of HSDJ or C394S resulted in slight retardation of the pOTC
      processing. These results indicate that HSDJ is involved in an early step(s) of
      protein import into mitochondria.

PMID- 9192729
TI  - cDNA cloning of nuclear localization signal binding protein NBP60, a rat
      homologue of lamin B receptor, and identification of binding sites of human lamin
      B receptor for nuclear localization signals and chromatin.
AB  - We previously purified and characterized a nuclear localization signal (NLS)
      binding protein, NBP60, in rat liver nuclear envelopes. In this study, we cloned
      and sequenced the cDNA of rat NBP60, and predicted an amino acid sequence
      comprising 620 amino acids. The sequence revealed that NBP60 is a rat homologue
      of lamin B receptor (LBR), and is 79 and 63% identical in amino acids to human
      and chicken LBR, respectively. Using three fusion proteins containing different
      parts of the amino-terminal domain of human LBR, it was shown that the stretch
      comprising amino acids 1 to 89, which contains a Ser-Arg rich region (RS region),
      binds to nucleoplasmin and that the binding was inhibited by a common NLS
      peptide. These results suggested that the amino-terminal domain of LBR contains
      an NLS-binding site. Furthermore, it was shown that the stretch comprising amino
      acids 1 to 53, which does not contain the RS region or the predicted DNA-binding
      site, binds to Xenopus laevis sperm chromatin.

PMID- 9192731
TI  - Interaction of the pre-domain of interleukin-1 with the mature domain.
AB  - The two interleukin 1 precursors (preIL-1alpha and beta) with a molecular mass of
      33 kDa are proteolytically processed to the mature carboxyl-terminal 17-kDa
      proteins. In this study we newly developed a monoclonal antibody against the
      precursor domain of IL-1beta (ED7), of which the binding to preIL-1beta was
      hindered by a polyclonal antibody against the mature domain of IL-1beta.
      Immunoprecipitation of limited proteolysed preIL-1beta by ED7 suggested that the
      epitope for ED7 may not be localized at the junction between preIL-1beta and
      mature IL-1beta. We therefore examined the possibility that the pre-domain of IL
      1beta might interact with the mature domain by using chemical cross-linking. V8
      protease yielded a mature 17.5-kDa protein from untreated preIL-1beta, but not
      chemically cross-linked preIL-1beta. However, cleavage of the cross-link with 2
      mercaptoethanol liberated a mature 17.5-kDa protein from preIL-1beta, suggesting
      that the pre-domains of IL-1beta might interact with the mature domain. Similar
      phenomena were observed with preIL-1alpha. Such an intermolecular interaction may
      inhibit or modulate the biological activity of mature IL-1s.

PMID- 9192732
TI  - Two genes encoding serine protease homologues in Serratia marcescens and
      characterization of their products in Escherichia coli.
AB  - A serine protease (SSP) of Serratia marcescens is one of the extracellular
      enzymes secreted from this Gram-negative bacterium. SSP is produced as a large
      precursor and converted to a mature protein by cleavages removing an NH2-terminal
      signal sequence and a COOH-terminal pro-region. This COOH-terminal pro-region is
      integrated into the outer membrane and has a functional role for the export of
      the mature protein across the outer membrane. Southern hybridization analysis
      with a DNA fragment encoding the COOH-terminal pro-region as the probe showed a
      wide distribution of nucleotide sequences encoding SSP exporter-like proteins
      among Serratia species. Moreover, S. marcescens IFO 3046, from which the ssp gene
      had been cloned, was found to contain two ssp homologues (ssp-h1 and ssp-h2).
      They were cloned and their nucleotide sequences were determined. The two ssp
      homologues were found to exist in tandem on the genome and their amino acid
      sequences showed 81% identity to each other. Both of them showed 55% identity in
      amino acid sequence to preproSSP. In addition, both showed end-to-end similarity
      to the 100 kDa serotype-specific antigen (Ssa1) of Pasteurella haemolytica.
      Escherichia coli JM105 containing ssp-h1 gene produced a 53 kDa protein
      corresponding to the NH2-terminal portion and a 49 kDa protein corresponding to
      the COOH-terminal portion, both of which were rigidly integrated in the outer
      membrane. Consistent with the significant similarity of the COOH-terminal
      portions of the homologues to that of SSP, they showed the ability to translocate
      the mature SSP part across the outer membrane into the medium. Furthermore, the
      NH2-terminal portion of the homologue was not translocated into the outer
      membrane without its COOH-terminal part. All of these data show that the SSP
      homologues are outer membrane proteins that are translocated into the outer
      membrane with the aid of the translocator function of their COOH-terminal part.

PMID- 9192733
TI  - Structural interlock between ligand-binding site and stalk-like region of beta1
      integrin revealed by a monoclonal antibody recognizing conformation-dependent
      epitope.
AB  - Integrin activation and sebsequent ligand binding to it are regulated by
      intracellular mechanisms called inside-out signaling, which are not fully
      understood and are accompanied by dynamic structural changes of the integrin
      molecule itself. A monoclonal antibody recognizing a conformation-dependent
      epitope on human beta1 integrin was produced and characterized in detail. This
      antibody, AG89, reacted with human integrin beta1 chain regardless of the alpha
      subunit. AG89 can recognize resting state beta1 integrin on the cells, but the
      reactivity is increased approximately 2-fold upon integrin activation by
      activating anti-beta1 antibodies and approximately 3-fold by Mn2+. Furthermore,
      occupation of the ligand-binding pocket by a soluble ligand (RGD peptide for
      alpha(v)beta1 and CS-1 peptide for alpha4beta1) resulted in maximum binding of
      AG89, indicating that the epitope for AG89 is exposed during the conformational
      changes of beta1 integrin upon activation/ligation. Epitope mapping by using
      interspecies chimeric beta1 revealed that the epitope for AG89 lies within
      residues 426-587, which corresponds to the cysteine-rich repeat structure located
      in the middle of the beta1 chain. The fact that binding of AG89 itself could
      activate the resting beta1 integrin indicates that exposure of the AG89 epitope
      in the membrane-proximal stalk-like domain and "opening" of the ligand-binding
      pocket at the outermost domain are physically linked. We propose that the
      integrin "signaling" is mediated by this direct physical transduction of
      conformational information along the integrin molecule.

PMID- 9192734
TI  - Transcriptional activation of H+/K+-ATPase genes by gastric GATA binding
      proteins.
AB  - H+/K+-ATPase (composed of alpha and beta subunits) and histamine H2 receptor are
      specifically expressed in gastric parietal cells. The GATA binding proteins (GATA
      GT1 and GATA-GT2, also called GATA-6 and GATA-4, respectively) originally found
      in the gastric mucosa recognized a sequence motif [gastric motif,
      (G/C)PuPu(G/C)NGAT(A/T)PuPy] in the upstream regions of the ATPase genes [Tamura,
      S., Wang, X.-H., Maeda, M., and Futai, M. (1993) Proc. Natl. Acad. Sci. USA 90,
      10876-10880]. These proteins activated the transcription of the reporter gene
      ligated downstream of the control region of the rat ATPase alpha or beta subunit
      gene but had no effect on the same reporter ligated downstream of the H2 receptor
      gene. Deletion analyses suggested that the upstream 249 (alpha gene) and 323
      (beta gene) base pair sequences from the first letter of the initiation codon are
      sufficient for activation by the GATA proteins. Interestingly, two and three
      gastric motifs are located near the TATA-boxes of the alpha and beta genes,
      respectively. Mutagenesis studies demonstrated that the two motifs proximal to
      the TATA-box sequences of the ATPase alpha and beta subunit genes were essential
      for the activation. These results suggest that both the alpha and beta subunit
      genes are regulated similarly by the GATA binding proteins. The expression system
      established in this study is a useful system for analyzing the roles of GATA
      proteins in transcriptional regulation of the H+/K+-ATPase gene.

PMID- 9192735
TI  - Renaturation, purification, and characterization of human plasminogen activator
      inhibitor type 2 (PAI-2) accumulated at high level in Escherichia coli.
AB  - Plasminogen activator inhibitor 2 (PAI-2) is an important regulator of
      plasminogen activation, which inhibits both tissue-type plasminogen activator
      (tPA) and urokinase-type plasminogen activator (uPA). In this study we have
      developed a high-level expression system by inserting a modified PAI-2 gene
      downstream of the T7 promoter. The expression level of recombinant PAI-2 amounted
      to 55-60% of total microbial protein. By efficient renaturation and one-step
      purification, the recombinant protein was purified to homogeneity. The specific
      activity and yield of recombinant PAI-2 reached 33,000 IU/mg and 10 mg per gram
      wet weight of Escherichia coli cells, respectively. The second-order rate
      constant for uPA was 2.6-2.8 x 10(6) M(-1) x s(-1).

PMID- 9192736
TI  - Identification of multiple regulatory elements of human L-histidine decarboxylase
      gene.
AB  - Previously, we reported the structure of human L-histidine decarboxylase gene. To
      identify the regions that regulate the tissue-specific expression of HDC, we
      constructed a fusion DNA with the 5'-flanking region from -1003 to +99 of the HDC
      gene and chloramphenicol acetyltransferase (CAT) gene, which was then transfected
      into human basophilic leukemia KU-812-F cells or human epithelial carcinoma HeLa
      cells. The 1102 bp DNA fragment stimulated the CAT activity in KU-812-F cells,
      but not in HeLa cells. CAT analysis with a series of 5'-deletion constructs of
      the HDC-CAT gene revealed the existence of two positive and one negative
      regulatory elements at -855 to -841 and -532 to -497 and -829 to -821,
      respectively. Sequence analysis showed a nuclear factor c-Myb binding motif,
      TAACTG, at position -520. Gel mobility shift analysis showed that the nuclear
      extract of KU-812-F cells, but not that of HeLa cells, contains a factor which
      can bind to this motif. These results suggest that the 5'-flanking region of the
      HDC gene contains multiple regulatory elements for HDC gene expression and that
      at least one element, including a c-Myb binding motif, is responsible for the
      tissue-specific expression of HDC.

PMID- 9192737
TI  - A novel human PACE4 isoform, PACE4E is an active processing protease containing a
      hydrophobic cluster at the carboxy terminus.
AB  - PACE4 is a processing protease which processes the precursor protein to the
      mature protein. Currently, four PACE4 isoforms have been reported [Tsuji, A. et
      al. (1994) Biochem. Biophys. Res. Commun. 200, 943 950]. In this study, we have
      cloned cDNA encoding a novel isoform, PACE4E, by screening the human brain
      cerebellum cDNA library and reverse transcriptase polymerase chain reaction
      analysis of total RNA from human hepatoma HepG2 cells. The PACE4E cDNA encoded an
      amino acid sequence of 975 residues. The sequence from the amino terminus to
      Arg900 of PACE4E was identical to the corresponding sequence of PACE4A, but the
      carboxy terminal sequence (75 residues) was unique and contained a hydrophobic
      cluster (Leu952-Gly968). PACE4E cDNA was transiently transfected in COS-1 cells,
      and the expressed proteins were a 112-kDa precursor form and a 105-kDa mature
      form. They were secreted into the culture medium, but their secretion was
      retarded compared with that of PACE4A. The expression of a mutant of PACE4E
      truncated up to the hydrophobic cluster from the carboxy terminus resulted in a
      remarkable increase in secretion level, suggesting that PACE4E tends to be
      retained intracellularly due to interaction with the membrane through the
      hydrophobic cluster. On the contrary, the transient expression experiment of
      PACE4C showed that only 68-kDa protein (precursor form) was detected in the cell
      and not secreted into the medium. In addition, coexpression experiment revealed
      that PACE4E was able to process the precursor form of von Willebrand factor to
      the mature form, but PACE4C did not process it.

PMID- 9192738
TI  - Potentiation of chemotactic peptide-induced superoxide generation by CD38
      ligation in human myeloid cell lines.
AB  - CD38 is a type II transmembrane glycoprotein possessing an NAD+ glycohydrolase
      activity in its extracellular domain. We previously reported that the ligation of
      CD38 by a monoclonal antibody (mAb), HB-7, induces the tyrosine phosphorylation
      of cellular proteins including p120(c-cbl) in differentiated human myeloid cell
      lines and that the phosphorylated p120(c-cbl) is capable of binding to
      phosphatidylinositol (PI) 3-kinase. In the present study, we found that the
      agonistic anti-CD38 mAb markedly potentiates superoxide generation stimulated by
      chemotactic formyl-Met-Leu-Phe receptors in the CD38-producing cells. HB-7
      neither generated superoxide by itself nor enhanced the cell response induced by
      phorbol 12-myristate acetate, indicating that the potentiating action of the anti
      CD38 mAb is specific for the stimulation by the GTP-binding protein (G1)-coupled
      membrane receptors. The potentiation by HB-7 was abolished by prior treatment of
      the cells with a tyrosine kinase inhibitor, pertussis toxin, or a potent PI 3
      kinase inhibitor, wortmannin. HB-7 also enhanced the product formation of PI 3
      kinase in response to the chemotactic receptor stimulation, without significant
      changes in the receptor-stimulated accumulations of inositol-1,4,5-trisphosphate,
      arachidonate release, and intracellular Ca2+. These results indicate that the
      CD38-induced tyrosine phosphorylation has a cross-talk with the chemotactic
      receptor/G1-mediated signal transduction pathway resulting in the enhancement of
      superoxide generation, probably through the activation of PI 3-kinase.

PMID- 9192739
TI  - Effect of ammonia starvation on hydroxylamine oxidoreductase activity of
      Nitrosomonas europaea.
AB  - A technique for detection of the activity of hydroxylamine oxidoreductase (HAO)
      involving denaturing SDS-polyacrylamide gels was developed. The activity of HAO
      of Nitrosomonas europaea was assayed using this technique, which revealed a
      single active band of 140 kDa. The HAO activity of other ammonia-oxidizers was
      also resistant to SDS, the molecular weights being identical to that of N.
      europaea. N. europaea cells starved of ammonia for up to 72 h retained a
      considerable amount of HAO, as detected on Western blot analysis, and a
      significant level of its activity, as found on assaying at the end of the
      starvation period. Only after 4 h incubation of starved N. europaea cells with
      2.0 mM ammonia was some increase in the HAO level observed. The results indicate
      that HAO remains highly stable during ammonia starvation of N. europaea.

PMID- 9192740
TI  - The binding ability to matrix proteins and the inhibitory effects on cell
      adhesion of synthetic peptides derived from a conserved sequence of integrins.
AB  - The beta peptide (113-125), derived from a conserved sequence of the beta subunit
      of integrins, was synthesized to investigate its adhesive properties to matrix
      proteins and the effects on cell adhesion to immobilized fibronectin. In this
      study, we observed that the biotinylated beta peptide was able to bind
      efficiently to immobilized fibronectin, fibrinogen, collagen Type I and
      vitronectin with different degrees of affinity. It was also demonstrated that
      biotinylated fibronectin or fibrinogen could bind to the coated beta peptide.
      This kind of binding, which might be non-covalent linkage, was partially blocked
      by coincubation with the peptide GRGDS or EDTA, but not by SDGRG. Cell adhesion
      experiments were performed to study the effect of the beta peptide. The data
      showed that the beta peptide partially inhibited both fibroblast L929 and MC3T3
      E1 osteoblastic cells from adhering to immobilized fibronectin in a dosage
      dependent manner. In the presence of 100 microM concentration of the beta
      peptide, the inhibition rate of cell adhesion was 34% for fibroblast L929 cells
      and 54.1% for MC 3T3-E1 osteoblastic cells. This research suggests that the beta
      peptide might act independently as an adhesive region of the beta subunit of
      integrins and may occupy the cell-binding site within fibronectin.

PMID- 9192741
TI  - Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets,
      is a normal constituent of human plasma and serum.
AB  - Although sphingosine 1-phosphate (Sph-1-P) is reportedly involved in diverse
      cellular processes and the physiological roles of this bioactive sphingolipid
      have been strongly suggested, few studies have revealed the presence of Sph-1-P
      in human samples, including body fluids and cells, under physiological
      conditions. In this study, we identified Sph-1-P as a normal constituent of human
      plasma and serum. The Sph-1-P levels in plasma and serum were 191+/-79 and 484+/
      82 pmol/ml (mean+/-SD, n=8), respectively. Furthermore, when Sph-1-P was measured
      in paired plasma and serum samples obtained from 6 healthy adults, the serum Sph
      1-P/plasma Sph-1-P ratio was found to be 2.65+/-1.26 (mean+/-SD). It is most
      likely that the source of discharged Sph-1-P during blood clotting is platelets,
      because platelets abundantly store Sph-1-P compared with other blood cells, and
      release part of their stored Sph-1-P extracellularly upon stimulation. We also
      studied Sph-1-P-related metabolism in plasma. [3H]Sph was stable and not
      metabolized at all in plasma, but was rapidly incorporated into platelets and
      metabolized mainly to Sph-1-P in platelet-rich plasma. [3H]Sph-1-P was found to
      be unchanged in plasma, revealing that plasma does not contain the enzymes needed
      for Sph-1-P degradation. In summary, platelets can convert Sph into Sph-1-P, and
      are storage sites for the latter in the blood. In view of the diverse biological
      effects of Sph-1-P, the release of Sph-1-P from activated platelets may be
      involved in a variety of physiological and pathophysiological processes,
      including thrombosis, hemostasis, atherosclerosis and wound healing.

PMID- 9192742
TI  - Binding mode of CA074, a specific irreversible inhibitor, to bovine cathepsin B
      as determined by X-ray crystal analysis of the complex.
AB  - The binding mode of CA074 [N-(L-3-trans-propylcarbamoyl-oxirane-2-carbonyl)-L
      isoleucyl-L-pr oline], a specific irreversible inhibitor, to bovine spleen
      cathepsin B was elucidated by X-ray crystal structure analysis of the complex at
      2.2 A resolution (conventional R=0.185). Inconsistently with our model used for
      the development of CA074, the L-isoleucyl-L-proline and propylcarbamoyl moieties
      are located at the S' and S subsites, respectively. This unexpected binding is
      primarily due to (i) similar extended chain conformations (due to the same S
      configurations) at the oxirane C2 and C3 atoms of CA074 and (ii) the just fit
      formation of double hydrogen bonds between the carboxyl oxygens of L-proline and
      the imidazole nitrogens of His-110 and His-111 residues (these residues are
      missing in papain, the tertiary structure of which was used for the design of
      CA074). The oxirane C3 atom possessing the P' substituent is covalently bound to
      the Cys-29 Sgamma atom (C3-Sgamma=1.79 A) and the S configuration is maintained.
      The present result will provide useful information for characterizing the
      substrate-specificity of cathepsin B.

PMID- 9192743
TI  - 1-Alkenyl group of ethanolamine plasmalogen derives mainly from de novo
      synthesized fatty alcohol within peroxisomes, but not extraperoxisomal fatty
      alcohol or fatty acid.
AB  - The origin of the 1-alkenyl group of ethanolamine plasmalogen was investigated.
      Three candidates were examined for the fatty alcohol forming the 1-alkenyl group.
      [1-(14)C]Hexadecanoic acid, [1-(14)C]hexadecanol, or [1-(14)C]lignoceric acid was
      administered to rats treated with 0.25% clofibrate-chow for 2 weeks. At 0.5, 1,
      2, 3, and 4 h after administration of the radiolabeled compound, rats were killed
      and ethanolamine-containing phosphoglyceride (EPG)-rich fraction was isolated
      from the liver. The components of the 1-radyl group in EPG-rich fraction were
      separated and the radioactivity was determined. The radiolabel after
      administration of [1-(14)C]hexadecanoic acid or [1-(14)C]hexadecanol was almost
      wholly incorporated into diacyl-type glycerophosphoethanolamine (GPE), and was
      predominantly found in hexadecanoic acid fraction. Therefore, the long-chain
      fatty acid may be incorporated intact into the diacyl groups, and the long-chain
      fatty alcohol may be similarly incorporated after oxidation to the acid. In
      contrast, the radiolabel after the administration of [1-(14)C]lignoceric acid was
      found in the 1-alkenyl group of ethanolamine plasmalogen. After hydrolysis of the
      1-alkenyl group by treatment of the plasmalogen with HCl vapor, the radiolabeled
      products were chiefly stearaldehyde and palmitaldehyde. The above data indicate
      that nascent fatty alcohol de novo synthesized from acetyl-CoA derived by
      peroxisomal beta-oxidation is almost exclusively used as the fatty alcohol
      forming the 1-alkenyl group of ethanolamine plasmalogen.

PMID- 9192744
TI  - Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase:
      regulation by autoinhibitory and visinin-like domains.
AB  - A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with
      a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain
      was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad.
      Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132].
      The mechanisms of CCaMK activation by calcium and calcium/calmodulin were
      investigated using various deletion mutants. The use of deletion mutants of CCaMK
      lacking either one, two, or all three calcium-binding EF hands indicated that all
      three calcium-binding sites in the visinin-like domain were crucial for the full
      calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was
      deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase
      activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the
      visinin-like domain containing three EF hands and the calmodulin-binding domain
      was constitutively active, indicating the presence of an autoinhibitory domain
      around the calmodulin-binding domain. By using various synthetic peptides and the
      constitutively active mutant, we have shown that CCaMK contains an autoinhibitory
      domain within the residues 322-340 which overlaps its calmodulin-binding domain.
      Kinetic studies with both ATP and the GS peptide substrate suggest that the
      autoinhibitory domain of CCaMK interacts only with the peptide substrate binding
      motif of the catalytic domain, but not with the ATP-binding motif.

PMID- 9192745
TI  - Clarification of an uncertain intron within the cDNA sequences of arrowhead
      proteinase inhibitors A and B.
AB  - An uncertain intron of 87 bp within the cDNA sequences of arrowhead proteinase
      inhibitors A and B was clarified. By site-directed mutation with either a stop
      codon inside the uncertain intron or mutated codons at both its 5' and 3' ends,
      it was proved that there was neither a translation intron nor a protein intron
      present in the cDNA sequences of proteinase inhibitors A and B. The primary
      structure of inhibitor B was then reexamined by mass spectrometry molecular
      weight determination and partial amino acid sequencing. A 38 residue peptide was
      derived by degradation of inhibitor B with lysylendopeptidase, and purified,
      which was not found in the previous work, and its N-terminal part was none other
      than the missed 29 residue peptide encoded by the uncertain intron. The 38
      residue peptide was very hydrophobic, while the 29 residue peptide it included
      was even more hydrophobic. The N-terminal part of the missed peptide was also
      aligned within a BrCN-degraded fragment of the inhibitor. In this paper the cause
      of the overlooking of this 29 residue peptide in the previous work and some
      unexpected problems which arose during the former sequence analysis are
      explained.

PMID- 9192746
TI  - A tribute to Jan Gosta Waldenstrom.

PMID- 9192747
TI  - Use of recombinant human erythropoietin outside the setting of uremia.

PMID- 9192748
TI  - Tissue factor pathway inhibitor blocks cellular effects of endotoxin by binding
      to endotoxin and interfering with transfer to CD14.
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type plasma protease inhibitor
      that inhibits factor Xa and the factor VIIa/tissue factor catalytic complex. It
      plays an important role in feedback inhibition of the coagulation cascade (Broze,
      Annu Rev Med 46:103, 1995). TFPI has also been used successfully to prevent
      lethality and attenuate coagulopathic responses in a baboon model of septic shock
      (Creasey et al, J Clin Invest 91:2850, 1993; and Carr et al, Circ Shock 44:126,
      1995). However, the mechanism of reduced mortality in these animals could not be
      explained merely by the anticoagulant effect of TFPI, because TFPI-treated
      animals also had a significantly depressed interleukin-6 response. Moreover,
      inhibition of coagulopathic responses by other anticoagulants has failed to block
      the organ damage or lethal effect of endotoxic shock (Coalson et al, Circ Shock
      5:423, 1978; Warr et al, Blood 75:1481, 1990; and Taylor et al, Blood 78:364,
      1991). We show here that recombinant TFPI can bind to endotoxin in vitro. This
      binding prevents interaction of endotoxin with both lipopolysaccharide binding
      protein and CD14, thereby blocking cellular responses.

PMID- 9192749
TI  - Detection of trisomy 12 and Rb-deletion in CD34+ cells of patients with B-cell
      chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is a slowly progressive disease
      characterized by the clonal expansion of CD5+/CD23+ B lymphocytes. The malignant
      transformation is assumed to occur at the level of mature B lymphocytes. We asked
      whether CD34+ progenitor cells are involved in the malignant process in B-CLL.
      Furthermore, we investigated the possibility of aberrant CD34 expression by the
      malignant B-cell clone. Bone marrow and peripheral blood samples from 75 patients
      with B-CLL were tested for the presence of trisomy 12 and deletion of the
      retinoblastoma gene (Rb) by fluorescence in situ hybridization. CD34+
      subpopulations were isolated by fluorescence-activated cell sorting and analyzed
      for the presence of the informative genetic marker. Bone marrow and peripheral
      blood samples of 10 B-CLL patients were analyzed for coexpression of
      CD34/CD5/CD20. Trisomy 12 was detected in 15 of 75 (20%) and Rb-deletion was
      detected in 6 of 30 patients (20%). In 7 patients with trisomy 12, hematopoietic
      progenitor cells were sorted, with the sort purity being between 85% and 99.8%.
      The genetic marker was detected in the CD34+/CD38+ cells as well as in the
      CD34+/38- subsets in 3 patients. Progenitor cells were also sorted in 2 patients
      with Rb-deletion. In 1 patient, Rb-deletion was present in 10% of CD34+/38+
      cells. In the other patient, Rb-deletion was neither detected in the CD34+/38+
      nor in the CD34+/CD38- subsets. In all 10 patients investigated for coexpression
      of CD34/CD5/CD20, we could not find a subpopulation coexpressing these markers.
      We conclude that trisomy 12 and Rb-deletion are present in a considerable subset
      of patients with B-CLL. In part of these patients, the genetic marker was
      detected at the level of CD34+ stem cells. CD34 expression is not related to an
      aberrant phenotype of the malignant B-cell clone. These results suggest that the
      malignant transformation in B-CLL may involve early hematopoietic stem cells and
      place a note of caution on future strategies using autologous stem cell
      transplantation.

PMID- 9192750
TI  - A retinoid-resistant acute promyelocytic leukemia subclone expresses a dominant
      negative PML-RAR alpha mutation.
AB  - The unique t(15;17) of acute promyelocytic leukemia (APL) fuses the PML gene with
      the retinoic acid receptor alpha (RAR alpha) gene. Although retinoic acid (RA)
      inhibits cell growth and induces differentiation in human APL cells, resistance
      to RA develops both in vitro and in patients. We have developed RA-resistant
      subclones of the human APL cell line, NB4, whose nuclear extracts display altered
      RA binding. In the RA-resistant subclone, R4, we find an absence of ligand
      binding of PML-RAR alpha associated with a point mutation changing a leucine to
      proline in the ligand-binding domain of the fusion PML-RAR alpha protein. In
      contrast to mutations in RAR alpha found in retinoid-resistant HL60 cells, in
      this NB4 subclone, the coexpressed RAR alpha remains wild-type. In vitro
      expression of a cloned PML-RAR alpha with the observed mutation in R4 confirms
      that this amino acid change causes the loss of ligand binding, but the mutant PML
      RAR alpha protein retains the ability to heterodimerize with RXR alpha and thus
      to bind to retinoid response elements (RAREs). This leads to a dominant negative
      block of transcription from RAREs that is dose-dependent and not relieved by RA.
      An unrearranged RAR alpha engineered with this mutation also lost ligand binding
      and inhibited transcription in a dominant negative manner. We then found that the
      mutant PML-RAR alpha selectively alters regulation of gene expression in the R4
      cell line. R4 cells have lost retinoid-regulation of RXR alpha and RAR beta and
      the RA-induced loss of PML-RAR alpha protein seen in NB4 cells, but retain
      retinoid-induction of CD18 and CD38. Thus, the R4 cell line provides data
      supporting the presence of an RAR alpha-mediated pathway that is independent from
      gene expression induced or repressed by PML-RAR alpha. The high level of retinoid
      resistance in vitro and in vivo of cells from some relapsed APL patients suggests
      similar molecular changes may occur clinically.

PMID- 9192751
TI  - Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial
      and smooth muscle cells.
AB  - There is evidence to suggest that elevated plasma levels of lipoprotein (a)
      [Lp(a)] represent a risk factor for the development of atherosclerotic vascular
      disease, but the mechanism by which this lipoprotein localizes to involved
      vessels is only partially understood. In view of studies suggesting a link
      between inflammation and atherosclerosis and our previous finding that leukocyte
      defensin modulates the interaction of plasminogen and tissue-type plasminogen
      activator with cultured human endothelial cells, we examined the effect of this
      peptide on the binding of Lp(a) to cultured vascular endothelium and vascular
      smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial cells
      approximately fourfold and to smooth muscle cells approximately sixfold. Defensin
      caused a comparable increase in the amount of Lp(a) internalized by each cell
      type, but Lp(a) internalized as a consequence of defensin being present was not
      degraded, resulting in a marked increase in the total amount of cell-associated
      lipoprotein. Abundant defensin was found in endothelium and in intimal smooth
      muscle cells of atherosclerotic human cerebral arteries, regions also invested
      with Lp(a). These studies suggest that defensin released from activated or
      senescent neutrophils may contribute to the localization and persistence of Lp(a)
      in human vessels and thereby predispose to the development of atherosclerosis.

PMID- 9192752
TI  - Hematopoietic potential and retroviral transduction of CD34+ Thy-1+ peripheral
      blood stem cells from asymptomatic human immunodeficiency virus type-1-infected
      individuals mobilized with granulocyte colony-stimulating factor.
AB  - The potential of hematopoietic stem cells (HSCs) from human immunodeficiency
      virus type-1 (HIV-1)-infected individuals, eg, self-renewal and multilineage
      differentiative capacity, might be perturbed due to the underlying disease. In
      this study, we assessed the HSC activity in the CD34+ Thy-1+ cell population of
      peripheral blood stem cells (PBSCs) of three asymptomatic HIV-1-infected
      individuals after granulocyte colony-stimulating factor (G-CSF; 10 microg/kg/d)
      mobilization. On day 4 of G-CSF treatment, 0.8% to 1% of the total blood
      mononuclear cells were CD34+. Leukapheresis followed by a two-step cell isolation
      process yielded a CD34+ Thy-1+ cell population of high purity (76% to 92% CD34+
      Thy-1+ cells). This cell population showed no evidence of HIV-1-containing cells
      based on a semiquantitative HIV-1 DNA polymerase chain reaction. Furthermore, the
      purified cells showed normal hematopoietic potential in in vitro clonogenic
      assays. Successful gene transfer into committed progenitor cells (colony-forming
      units-cells) and more primitive stem/progenitor cells (long-term culture colony
      forming cells) could be shown after amphotropic retroviral transduction. These
      data provide evidence that the CD34+ Thy-1+ stem cell compartment can be
      mobilized and enriched in early stage HIV-1-infected patients. Furthermore,
      successful transduction of this cell population as a prerequisite for stem cell
      based clinical gene therapy protocols was demonstrated.

PMID- 9192753
TI  - Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive
      cells in normal human bone marrow transplanted into immunodeficient mice.
AB  - Based on initial observations of human CD34+ Thy-1+ cells and long-term culture
      initiating cells (LTC-IC) in the bone marrow of some sublethally irradiated
      severe combined immunodeficient (SCID) mice transplanted intravenously with
      normal human marrow cells, and the subsequent finding that the NOD/LtSz-scid/scid
      (NOD/SCID) mouse supports higher levels of human cell engraftment, we undertook a
      series of time course experiments to examine posttransplant changes in the
      number, tissue distribution, cycling activity, and in vivo differentiation
      pattern of various human hematopoietic progenitor cell populations in this latter
      mouse model. These studies showed typical rapid posttransplant recovery curves
      for human CD34- CD19+ (B-lineage) cells, CD34+ granulopoietic, erythroid, and
      multilineage colony-forming cells (CFC), LTC-IC, and CD34+ Thy-1+ cells from a
      small initial population representing <0.1% of the original transplant. The most
      primitive human cell populations reached maximum values at 5 weeks
      posttransplant, after which they declined. More mature cell types peaked after
      another 5 weeks and then declined. A 2-week course of thrice weekly injections of
      human Steel factor, interleukin (IL)-3, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), and erythropoietin (administered just before the mice were
      killed for analysis) did not alter the pace of regeneration of either primitive
      or mature human hematopoietic cells, or their predominantly granulopoietic and B
      lymphoid pattern of differentiation, although a significant enhancing effect on
      the level of human cell engraftment sustained after 3 months was noted. Cycling
      studies showed the human CFC present at 4 to 5 weeks posttransplant to be rapidly
      proliferating even in mice not given human growth factors. However, by 10 weeks
      and thereafter, only quiescent human CFC were detected; interestingly, even in
      mice that were given the 2-week course of growth factor injections. These studies
      indicate the use of this model for future analysis of the properties and in vivo
      regulation of primitive human hematopoietic cells that possess in vivo
      repopulating ability.

PMID- 9192754
TI  - Expression and function of murine receptor tyrosine kinases, TIE and TEK, in
      hematopoietic stem cells.
AB  - Two highly related receptor tyrosine kinases, TIE and TEK, comprise a family of
      endothelial cell-specific kinase. We established monoclonal antibodies against
      them and performed detailed analyses on their expression and function in murine
      hematopoietic stem cells (HSCs). TIE and TEK were expressed on 23.7% and 33.3% of
      lineage marker-negative, c-Kit+ and Sca-1+ (Lin- c-Kit+ Sca-1+) HSCs that contain
      the majority of day-12 colony-forming units-spleen (CFU-S) and long-term
      reconstituting cells, but not committed progenitor cells. Lin- c-Kit+ Sca-1+
      cells were further divided by the expression of TIE and TEK. TIE+ and TEK+ HSCs
      as well as each negative counterpart contained high proliferative potential
      colony-forming cells and differentiated into lymphoid and myeloid progenies both
      in vitro and in vivo. However, day-12 CFU-S were enriched in TIE+ and TEK+ HSCs.
      Our findings define TIE and TEK as novel stem cell marker antigens that segregate
      day-12 CFU-S, and provide evidence of novel signaling pathways that are involved
      in the functional regulation of HSCs at a specific stage of differentiation,
      particularly of day-12 CFU-S.

PMID- 9192755
TI  - Erythropoietin induces tyrosine phosphorylation of the interleukin-3 receptor
      beta subunit (betaIL3) and recruitment of Stat5 to possible Stat5-docking sites
      in betaIL3.
AB  - The receptors for erythropoietin (Epo) and interleukin-3 (IL-3) both induce the
      ligand-dependent activation of the Jak2 tyrosine kinase. Activated Jak2 then
      phosphorylates these receptors and thereby recruits various signaling molecules
      containing the Src homology (SH)-2 domain, including Stat5, to the tyrosine
      phosphorylated receptors. In the present study, we demonstrate that Epo
      stimulation induces unidirectional cross-phosphorylation of the IL-3 receptor
      beta subunit (betaIL3) on tyrosines and its rapid and transient association with
      Stat5 in murine IL-3-dependent cell lines engineered to express the Epo receptor
      (EpoR). Using cell lines expressing various EpoR mutants, it was demonstrated
      that the Epo-induced tyrosine phosphorylation of betaIL3 is dependent on the
      membrane-proximal EpoR cytoplasmic region involved in the activation of Jak2, but
      not on the extracellular and transmembrane regions or on the carboxy-terminal 145
      amino acid region containing all the intracellular tyrosine residues. It was also
      shown that IL-3 induces rapid and dose-dependent association of Jak2 with
      betaIL3. However, Epo failed to induce any detectable association of betaIL3 with
      Jak2 or the EpoR. The present study also demonstrates that in IL-3-stimulated
      cells, an ovine Stat5 mutant harboring a substitution of Tyr694 to Phe, which
      abolishes the tyrosine phosphorylation required for activation, fails to dimerize
      with endogenous Stat5, shows sustained binding with tyrosine-phosphorylated
      betaIL3, and inhibits the tyrosine phosphorylation of endogenous Stat5. These
      results suggest that betaIL3 may have Stat5 docking sites, similar to those found
      in the EpoR, that facilitate the activation of Stat5 by Jak2 and raise the
      possibility that Epo may cross-activate or transmodulate the IL-3 receptor
      signaling pathways.

PMID- 9192756
TI  - In vitro maintenance of highly purified, transplantable hematopoietic stem cells.
AB  - The cellular and molecular mechanisms that regulate the most primitive
      hematopoietic stem cell are not well understood. We have undertaken a systematic
      dissection of the complex hematopoietic microenvironment to define some of these
      mechanisms. An extensive panel of immortalized stromal cell lines from murine
      fetal liver were established and characterized. Collectively, these cell lines
      display extensive heterogeneity in their in vitro hematopoietic supportive
      capacity. In the current studies, we describe a long-term in vitro culture system
      using a single stromal cell clone (AFT024) that qualitatively and quantitatively
      supports transplantable stem cell activity present in highly purified
      populations. We show multilineage reconstitution in mice that received the
      equivalent of as few as 100 purified bone marrow and fetal liver stem cells
      cultured for 4 to 7 weeks on AFT024. The cultured stem cells meet all functional
      criteria currently ascribed to the most primitive stem cell population. The
      levels of stem cell activity present after 5 weeks of coculture with AFT024 far
      exceed those present in short-term cytokine-supported cultures. In addition,
      maintenance of input levels of transplantable stem cell activity is accompanied
      by expansion of other classes of stem/progenitor cells. This suggests that the
      stem/progenitor cell population is actively proliferating in culture and that the
      AFT024 cell line provides a milieu that stimulates progenitor cell proliferation
      while maintaining in vivo repopulating activity.

PMID- 9192757
TI  - The carbohydrate moiety of factor V modulates inactivation by activated protein
      C.
AB  - An important risk factor for thrombosis is the polymorphism R506Q in factor V
      that causes resistance of factor Va to proteolytic inactivation by activated
      protein C (APC). To study the potential influence of the carbohydrate moieties of
      factor Va on its inactivation by APC, factor V was subjected to mild
      deglycosylation (neuraminidase plus N-glycanase) under nondenaturing conditions.
      The APC resistance ratio values (ratio of activated partial thromboplastin time
      [APTT] clotting times with and without APC) of the treated factor V were
      increased (2.4 to 3.4) as measured in APTT assays. O-glycanase treatment of
      factor V did not change the APC resistance ratio. The procoagulant activity of
      factor V as well as its activation by thrombin was not affected by mild
      deglycosylation. Treatment of factor V with neuraminidase and N-glycanase mainly
      altered the electrophoretic mobility of the factor Va heavy chain, whereas
      treatment with O-glycanase changed the mobility of the connecting region. This
      suggests that the removal of the N-linked carbohydrates from the heavy chain of
      factor Va, which is the substrate for APC, is responsible for the increase in
      susceptibility to inactivation by APC. Thus, variability in carbohydrate could
      account for some of the known variability in APC resistance ratios, including the
      presence of borderline or low APC resistance ratios among patients who lack the
      R506Q mutation.

PMID- 9192758
TI  - Role of glycoprotein V in the formation of the platelet high-affinity thrombin
      binding site.
AB  - The glycoprotein (GP) Ib-IX-V complex contains a high-affinity binding site for
      thrombin on the platelet surface with a poorly defined role in platelet
      activation by this agonist. Four polypeptides comprise the complex: GP Ib alpha,
      GP Ib beta, GP IX, and GP V. The site within the complex that binds thrombin has
      been localized to a 45-kD region at the amino terminus of GP Ib alpha, which also
      contains the site through which the complex interacts with von Willebrand factor.
      A GP Ib-IX complex that lacks GP V can be efficiently expressed on the surface of
      transfected cells. We examined the ability of L cells expressing the GP Ib-IX
      complex (L2H cells) to bind thrombin at high affinity, and found no increase over
      the level of thrombin binding to control L cells. Because it is one of the few
      substrates for thrombin on the platelet surface, GP V has also been implicated as
      possibly participating in thrombin's actions on the platelet. To examine the role
      of GP V in forming the high-affinity thrombin-binding site, we compared the
      binding of thrombin to L2H cells versus cells that express the entire GP Ib-IX-V
      complex (L2H/V cells). Surface expression of GP Ib alpha was equivalent in these
      two stable cell lines. Thrombin binding to L2H/V cells was detectable at 0.25
      nmol/L thrombin and reached a plateau at 1 nmol/L. No binding to L2H cells was
      detectable at these concentrations. Comparable results were obtained when
      thrombin binding to L2H cells transiently expressing GP V was compared with its
      binding to sham-transfected L2H cells. Again, only cells transiently expressing
      GP V bound thrombin specifically. As with the platelet polypeptide, thrombin
      cleaved GP V from the surface of L2H/V cells. To test whether GP V cleavage was
      required for enhancing thrombin binding to the complex, we tested the binding of
      enzymatically inactive D-phenylalanyl-L-prolyl-L-arginine chloromethylketone
      (PPACK)-thrombin to L2H and L2H/V cells. Like native thrombin, PPACK-thrombin at
      1 nmol/L bound only to L2H/V cells, indicating that GP V cleavage is not a
      prerequisite for the formation of the high-affinity thrombin receptor. These data
      provide the first indication of a physiologic function for GP V, and suggest that
      formation of the high-affinity thrombin receptor on the platelet surface has
      complex allosteric requirements.

PMID- 9192759
TI  - Genetic and phenotypic analysis of a large (122-member) protein S-deficient
      kindred provides an explanation for the familial coexistence of type I and type
      III plasma phenotypes.
AB  - Protein S deficiency is a known risk factor for thrombosis. The coexistence of
      phenotypic type I (reduction in total and free antigen) and type III (reduction
      in free antigen only) protein S deficiencies in 14 of 18 families was recently
      reported. We investigated the cause of this phenotypic variation in the largest
      of these families (122 family members, including 44 affected individuals) using
      both molecular genetic and phenotypic analysis. We have identified a sole
      causative mutation (Gly295Val) in three family members representative of the
      variable phenotype. Complete cosegregation of the mutation with reduced free
      protein S antigen levels was found, regardless of the total antigen level.
      Analysis of phenotypic data showed high correlations between total protein S
      antigen and age in both normal and protein S-deficient family members,
      irrespective of gender. Free protein S antigen levels were not influenced by age,
      a finding explained by an association between beta-chain containing C4b-binding
      protein (C4bBP-beta+) antigen levels and age. We propose that the identified
      Gly295Val mutation causes quantitative, or type I, protein S deficiency, and that
      as age increases the total protein S antigen level normalizes with respect to the
      reference plasma pool, giving rise to a type III protein S-deficient phenotype.

PMID- 9192760
TI  - The missense mutation Arg593 --> Cys is related to antibody formation in a
      patient with mild hemophilia A.
AB  - The development of inhibitory antibodies to factor VIII in patients affected by a
      mild form of hemophilia A (factor VIII > 0.05 IU/mL) is considered a rare event.
      In this study, we evaluated the relationship between genotype and anti-factor
      VIII antibody formation in a patient with mild hemophilia A. Mutation analysis
      showed that a missense mutation in the factor VIII gene leading to replacement of
      Arg593 by Cys in the A2 domain of factor VIII was associated with hemophilia A in
      this patient. The anti-factor VIII antibodies present in the patient's plasma
      were characterized using metabolically labeled factor VIII fragments expressed in
      insect cells. The anti-factor VIII antibodies, composed of subclasses IgG2 and
      IgG4, reacted with both the fragment corresponding to the factor VIII heavy chain
      and the A2 domain. The Arg593 --> Cys substitution was introduced into the cDNA
      encoding the A2 domain of factor VIII and the resulting construct was expressed
      in insect cells. Strikingly, the metabolically labeled A2 domain carrying the
      Arg593 --> Cys mutation was not recognized by the anti-factor VIII antibodies
      present in the plasma of the patient. These data indicate that the anti-factor
      VIII antibodies are exclusively directed against exogenous factor VIII. This
      strongly suggests that the Arg593 --> Cys substitution results in recognition of
      wild-type factor VIII as nonself and is thereby related to the formation of anti
      factor VIII antibodies after factor VIII replacement therapy in this particular
      patient.

PMID- 9192761
TI  - Thrombin generation by apoptotic vascular smooth muscle cells.
AB  - Thrombin activation requires assembly of a prothrombinase complex of activated
      coagulation factors on an anionic phospholipid surface, classically provided by
      activated platelets. We have previously shown that anionic phosphatidylserine is
      exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after
      serum withdrawal. In this study, using a chromogenic assay, we have shown
      thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area
      under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak
      thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the
      apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003
      for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets
      (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2).
      Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8
      nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001
      for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than
      after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human
      coronary atherosclerotic plaques that apoptose even in serum also generated
      thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude
      that apoptotic VSMCs possess a significant thrombin-generating capacity secondary
      to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques
      may allow local thrombin activation, thereby contributing to disease progression.

PMID- 9192762
TI  - Reassessment of protein tyrosine phosphorylation in thrombasthenic platelets:
      evidence that phosphorylation of cortactin and a 64-kD protein is dependent on
      thrombin activation and integrin alphaIIb beta3.
AB  - Tyrosine phosphorylation of a number of platelet proteins is dependent on
      platelet integrin alphaIIb beta3 (also termed GPIIb-IIIa) and its engagement in
      aggregation. For instance, in type I thrombasthenic platelets, which lack
      alphaIIb beta3 and do not aggregate, several substrates are either poorly or not
      phosphorylated. We have compared thrombasthenic platelets of type I, type II (15%
      alphaIIb beta3, functional), and variant type (50% alphaIIb beta3, no fibrinogen
      binding). The platelets from the three patients exhibited the same low tyrosine
      phosphorylation profiles, confirming the key role of functional alphaIIb beta3 in
      initiating protein tyrosine phosphorylation. We noted that in addition to the
      characteristic absence of the 100 to 105 kD doublet, a 77 to 80 kD doublet and to
      a lesser extent a 64-kD band, exhibited low phosphorylation kinetics, but with
      normal initial phosphorylation rates (up to 60 seconds). Similar results were
      obtained by inhibition of thrombin aggregation of control platelets by alphaIIb
      beta3 antagonists (the RGDS peptide or the monoclonal antibody 10E5), or in the
      absence of stirring (fibrinogen binding, but no aggregation). These results
      suggest that tyrosine phosphorylation of the 77 to 80 kD doublet, identified by
      immunoprecipitation as the cytoskeletal protein cortactin, and the 64 kD band are
      dependent both on thrombin activation during early steps and on the late steps of
      alphaIIb beta3 engagement in aggregation. Implications as to involvement of step
      specific kinase and/or phosphatase activities are discussed.

PMID- 9192763
TI  - The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus
      aureus-induced disseminated intravascular coagulation in guinea pigs: substantial
      reduction in mortality and morbidity.
AB  - An animal model of gram-positive septicemia was developed to evaluate the effects
      of antithrombin (AT) concentrates on morbidity, mortality, and laboratory
      consequences of disseminated intravascular coagulation (DIC). DIC was induced in
      guinea pigs by infusing Staphylococcus aureus (SA) isolated from blood cultures
      of patients with DIC (DIC-SA) or without DIC (non-DIC-SA). The non-DIC-SA animals
      and animals infused with sterile saline served as controls. Varying doses of AT
      were administered either 30 minutes or 24 hours after infusion of SA. DIC was
      confirmed within 4 hours by changes in prothrombin time, activated partial
      thromboplastin time, fibrinogen, fibrinogen-fibrin degradation products, and AT
      activity. Clinical bleeding was also evident. Mortality of untreated DIC-SA
      animals was 36% within 24 hours and up to 75% by 72 hours. Intervention with any
      dose of AT between 125 and 1,000 IU/kg 30 minutes after DIC-SA infusion was
      associated with 100% survival (P < or = .05 in the 250 IU/kg group) and sustained
      increases in AT activity and fibrinogen concentrations (P < or = .05). When AT
      was administered in combination with low molecular weight heparin (LMWH) or if
      LMWH was adminstered alone, mortality from DIC-SA was slightly, but not
      significantly reduced compared with untreated DIC-SA. Gross hemorrhage was
      observed premortem and at autopsy in all of the DIC-SA animals but in
      substantially fewer animals that received AT (P < or = .001 in the 250, 500, and
      1,000 IU/kg groups). In contrast, groups treated with LMWH, alone or with AT,
      experienced hemorrhage and appeared to develop pathologic DIC. Fibrin formation
      in end-organs was detected in all guinea pigs in the untreated DIC-SA group and
      in the groups treated with 125 IU/kg AT and LMWH alone. AT doses between 250 and
      1,000 IU/kg administered 30 minutes after DIC-SA infusion prevented fibrin
      formation in end-organs (P < or = .001 in the 250 and 1,000 IU/kg groups). AT
      administered 24 hours after DIC-SA could not reverse pre-existing histopathologic
      evidence of DIC but favorably affected survival, which reached statistical
      significance in the 1,000 IU/kg AT group (P < or = .025). In summary,
      suprapharmacologic doses of AT concentrate significantly decreased morbidity and
      mortality and ameliorated adverse changes in laboratory measures induced by DIC
      SA in this guinea pig model and were not associated with untoward hemorrhagic
      complications. These findings provide justification for studying the use of AT
      therapy in patients with DIC-SA.

PMID- 9192764
TI  - Frequency of immune thrombocytopenia in newborns: a prospective study. Immune
      Thrombocytopenia Working Group.
AB  - Thrombocytopenia is a common condition in distressed newborns, but little is
      known about thrombocytopenia in an unselected cohort of neonates. In an attempt
      to address this issue, a multicenter prospective study was conducted in three
      obstetrical wards of AP-HP in Paris. We found the frequency of neonatal
      thrombocytopenia (<150 x 10(9)/L) to approximate 0.9% (48 of 5,632 appropriate
      samples). An immune mechanism was likely to be the cause of thrombocytopenia in
      10 of the 33 cases studied, implying an incidence of 0.3% of immune neonatal
      thrombocytopenia in the general population. The frequency of alloimmune
      thrombocytopenia was 1.5/1,000 liveborn neonates, and 1/1,000 when considering
      anti-HPA-1a allo-immunization. Because thrombocytopenia, whatever its cause, was
      often silent and delayed, it appears that the only way to detect neonatal
      thrombocytopenia in time to prevent its potential disastrous complications would
      be to perform a systematic neonatal blood sampling for platelet count. All cases
      of ascertained thrombocytopenia should then be screened for an immune mechanism
      to enable early detection of autoimmune diseases in mothers and careful
      monitoring of subsequent pregnancies and deliveries, leading to appropriate
      prevention of potential severe deleterious effects in the offspring.

PMID- 9192765
TI  - The conversion of fibrinogen to fibrin: recombinant fibrinogen typifies plasma
      fibrinogen.
AB  - Plasma fibrinogen is a mixture of multiple molecular forms arising mainly through
      alternative mRNA processing and subsequent posttranslational modification.
      Recombinant fibrinogen is synthesized without alternative mRNA processing in a
      cultured cell system that may generate novel posttranslational modifications.
      Thus, to show that recombinant fibrinogen can serve as a functional model for
      plasma fibrinogen, we have examined the conversion of fibrinogen to fibrin,
      comparing the recombinant with the plasma protein. We examined the kinetics of
      (1) thrombin-catalyzed fibrinopeptide release, (2) thrombin-catalyzed
      polymerization of fibrinogen, (3) the polymerization of fibrin monomers, and (4)
      FXIIIa-catalyzed cross-link formation. We saw small differences in
      polymerization, suggesting that the ordered assembly of protofibrils and fibers
      was not identical. In all other analyses, we found that plasma fibrinogen and
      recombinant fibrinogen were remarkably similar. Using electron microscopy, we
      examined the structures of individual fibrinogen molecules and fibrin clots.
      Individual fibrinogen molecules were predominantly three nodule structures for
      both recombinant and plasma proteins. Both samples also displayed four nodule
      structures, but fewer four nodule structures were found with recombinant
      fibrinogen. Fibrin clot structures were essentially indistinguishable. We
      concluded that recombinant fibrinogen can serve as a accurate model for plasma
      fibrinogen.

PMID- 9192766
TI  - Interleukin-13 in combination with CD40 ligand potently inhibits apoptosis in
      human B lymphocytes: upregulation of Bcl-xL and Mcl-1.
AB  - Interleukin-13 (IL-13) is a novel T-cell-derived cytokine with IL-4-like effects
      on many cell types. In human B lymphocytes, IL-13 induces activation, stimulates
      proliferation in combination with anti-IgM or anti-CD40 antibodies, and directs
      Ig isotype switching towards IgE and IgG4 isotypes. We show here that IL-13 also
      regulates human B-cell apoptosis. IL-13 reduced spontaneous apoptosis of
      peripheral blood B cells in vitro, as shown by measurement of DNA fragmentation
      using the TUNEL and Nicoletti assays. The inhibition of cell death by IL-13 alone
      was significant but modest, but was potently enhanced in combination with CD40
      ligand (CD40L), a survival stimulus for B cells by itself. Interestingly, IL-13
      increased the expression of CD40 on peripheral blood B cells, providing a
      possible mechanism for the observed synergy. IL-13 alone was a less potent
      inhibitor of apoptosis than IL-4. Moreover, there was no additive effect of
      combining IL-4 and IL-13 at supraoptimal concentrations, which is consistent with
      the notion that the IL-4 and IL-13 binding sites share a common signaling
      subunit. The combination of IL-13 with CD40L augmented the expression of the Bcl
      2 homologues Bcl-xL and Mcl-1, suggesting this as a possible intracellular
      mechanism of induced survival. By contrast, levels of Bcl-2, and two other Bcl-2
      family members, Bax and Bak, remained unaltered. Given the importance of the CD40
      CD40L interaction in B-cell responses, these results suggest a significant role
      of IL-13 in the regulation of B-cell apoptosis.

PMID- 9192767
TI  - Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy
      is established.
AB  - The majority of BALB/c mice immunized with the BCL1 lymphoma-derived idiotype
      (Id+) IgM and subsequently challenged with BCL1 tumor cells develop a state of
      tumor dormancy. The vast majority of dormant lymphoma cells are in cell cycle
      arrest, but there are also residual replicating cells. In the present studies, we
      attempted to define features of both the dormant lymphoma cells and the host that
      lead to escape from dormancy. Escape from dormancy occurs at a steady rate over a
      2-year period, suggesting that it is a stochastic process. We found that, in the
      majority of mice, escape was due to the emergence of genetic variants that were
      no longer susceptible to the anti-Id-mediated induction of dormancy. Ten percent
      of these variants were Id-; the remainder were Id+ but could grow in the presence
      of anti-Id antibodies, suggesting that there were mutations in molecules involved
      in one or more mIg-mediated negative-signaling pathways. In two of five such
      escapees, alterations in either Syk, HS1, and/or Lyn were observed. In a small
      percentage of mice, a low titer of circulating anti-Id antibody before tumor
      challenge correlated with a subsequent, more rapid loss of dormancy.

PMID- 9192768
TI  - Chimeric CLL-1 antibody fusion proteins containing granulocyte-macrophage colony
      stimulating factor or interleukin-2 with specificity for B-cell malignancies
      exhibit enhanced effector functions while retaining tumor targeting properties.
AB  - Although monoclonal antibody (MoAb) therapy of the human malignant lymphomas has
      shown success in clinical trials, its full potential for the treatment of
      hematologic malignancies has yet to be realized. To expand the clinical potential
      of a promising human-mouse chimeric antihuman B-cell MoAb (chCLL-1) constructed
      using the variable domains cloned from the murine Lym-2 (muLym-2) hybridoma,
      fusion proteins containing granulocyte-macrophage colony-stimulating factor (GM
      CSF) (chCLL-1/GM-CSF) or interleukin (IL)-2 (chCLL-1/IL-2) were generated and
      evaluated for in vitro cytotoxicity and in vivo tumor targeting. The glutamine
      synthetase gene amplification system was employed for high level expression of
      the recombinant fusion proteins. Antigenic specificity was confirmed by a
      competition radioimmunoassay against ARH-77 human myeloma cells. The activity of
      chCLL-1/GM-CSF was established by a colony formation assay, and the bioactivity
      of chCLL-1/IL-2 was confirmed by supporting the growth of an IL-2-dependent T
      cell line. Antibody-dependent cellular cytotoxicity against ARH-77 target cells
      demonstrated that both fusion proteins mediate enhanced tumor cell lysis by human
      mononuclear cells. Finally, biodistribution and imaging studies in nude mice
      bearing ARH-77 xenografts indicated that the fusion proteins specifically target
      the tumors. These in vitro and in vivo data suggest that chCLL-1/GM-CSF and chCLL
      1/IL-2 have potential as immunotherapeutic reagents for the treatment of B-cell
      malignancies.

PMID- 9192769
TI  - Molecular cloning and characterization of a cDNA, CHEMR1, encoding a chemokine
      receptor with a homology to the human C-C chemokine receptor, CCR-4.
AB  - Chemokines refer to a rapidly expanding family of small cytokines whose primary
      function is recruitment of leukocytes to inflammatory sites. These are known to
      bind to seven-transmembrane-domain containing receptors. A cDNA clone, CHEMR1,
      resembling the typical G protein-coupled receptor, was isolated from a mouse
      cytotoxic T-lymphocyte (CTL) library. Northern blot analysis in mouse cell lines
      suggests that its expression is found in a variety of cells, including T cells, B
      cells, and macrophages. The CHEMR1 gene Scya3r2 is a single-copy gene whose open
      reading frame may be in a single exon and maps to the distal region of mouse Chr
      9 where the mouse macrophage inflammatory protein-1alpha (MIP-1alpha) receptor
      gene Scya3r and two related C-C chemokine receptor-like genes reside. Amino acid
      sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating
      that CHEMR1 is likely to be a mouse CCR-4. Binding assays using 125I-labeled C-C
      chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha,
      RANTES, or MIP-1beta, whereas CCR-1 binds MIP-1alpha and RANTES. Our result is
      different from the reported properties of human CCR-4. This suggests that CHEMR1
      may be a receptor for unidentified C-C chemokine or a low-affinity receptor for
      MIP-1alpha.

PMID- 9192770
TI  - Interleukin-10 inhibits interferon-gamma-induced intercellular adhesion molecule
      1 gene transcription in human monocytes.
AB  - Interleukin-10 (IL-10) is a potent monocyte regulatory cytokine that inhibits
      gene expression of proinflammatory mediators. In this study, we investigated the
      mechanism by which IL-10 downregulates expression of intercellular adhesion
      molecule-1 (ICAM-1) on the cell surface of normal human monocytes activated with
      interferon-gamma (IFN-gamma). IL-10 inhibition of IFN-gamma-induced ICAM-1
      expression was apparent as early as 3 hours and was blocked by an anti-IL-10
      antibody but not by an isotype-matched control antibody. Northern blot analysis
      showed that IL-10 reduced the accumulation of ICAM-1 mRNA in IFN-gamma-stimulated
      monocytes. IL-10 inhibition of ICAM-1 steady-state mRNA was detected at 3 hours
      and remained at 24 hours. Nuclear run-on transcription assays showed that IL-10
      inhibited the rate of IFN-gamma-induced transcription of the ICAM-1 gene, and
      mRNA stability studies showed that IL-10 did not alter the half-life of IFN-gamma
      induced ICAM-1 message. Thus, IL-10 inhibits IFN-gamma-induced ICAM-1 expression
      in monocytes primarily at the level of gene transcription. Activation of IFN
      gamma-responsive genes requires tyrosine phosphorylation of the transcriptional
      factor STAT-1alpha (signal transducer and activator of transcription-1alpha).
      However, IL-10 did not affect IFN-gamma-induced tyrosine phosphorylation of STAT
      1alpha or alter STAT-1alpha binding to the IFN-gamma response element (IRE) in
      the ICAM-1 promoter. Instead, IL-10 prevented IFN-gamma-induced binding activity
      at the NF-kappaB site of the tumor necrosis factor alpha (TNF-alpha)-responsive
      NF-kappaB/C-EBP composite element in the ICAM-1 promoter. These data indicate
      that IL-10 inhibits IFN-gamma-induced transcription of the ICAM-1 gene by a
      regulatory mechanism that may involve NF-kappaB.

PMID- 9192771
TI  - Retinoid induced apoptosis in leukemia cells through a retinoic acid nuclear
      receptor-independent pathway.
AB  - Trans retinoic acid (RA) has proven to be a potent therapeutic agent in the
      treatment of acute promyelocytic leukemia. Unfortunately, other subtypes of acute
      myelogenous leukemia are resistant to the antiproliferative and differentiating
      effects of RA. In this report, we describe a novel retinoid 6-[3-(1-adamantyl)-4
      hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN; CD437) that not only totally
      inhibits the proliferation of RA-resistant leukemic cell lines HL-60R and K562
      but also induces apoptosis in these cells. Exposure of HL-60R to CD437 results in
      the rapid (within 30 minutes) increase of the cyclin-dependent kinase inhibitor
      p21(waf1/cip1) as well as GADD45 mRNA. Manifestations of CD437-mediated
      programmed cell death are noted within 2 hours, as indicated by both the cleavage
      and activation of the CPP32 protease and cleavage of poly (ADP-ribose)
      polymerase. This is followed by cleavage of bcl-2 and internucleosomal DNA
      degradation. HL-60R cells do not express the retinoid nuclear receptor RAR beta
      and RAR gamma and express a truncated RAR alpha. Thus, CD437 induction of
      p21(waf1/cip1) and GADD45 mRNAs and apoptosis occurs through a unique mechanism
      not involving the retinoid nuclear receptors. CD437 represents a unique retinoid
      with therapeutic potential in the treatment of myeloid leukemia.

PMID- 9192772
TI  - Bcl-2 does not protect Burkitt's lymphoma cells from oxidant-induced cell death.
AB  - Bcl-2 is an oncogene that confers deregulated growth potential to B lymphocytes
      through its ability to inhibit apoptotic cell death. A specific molecular
      activity for the Bcl-2 protein has not been identified, but several lines of
      evidence have supported a role in protection of cells from oxidative stress. We
      investigated whether there is a correlation between expression of high levels of
      Bcl-2 and susceptibility of human Burkitt's lymphoma cell lines to H2O2-induced
      killing. The amount of H2O2 required to kill 50% of cells in 24 hours varied
      widely in the seven different lymphoma cell lines that were tested, ranging from
      35 to 500 micromol/L H2O2. However, expression of high levels of endogenous Bcl-2
      did not protect the cells from H2O2-induced killing, even though it was effective
      in protecting the cells from apoptosis induced by agents such as A23187. Thus,
      Bcl-2 was functional in preventing apoptosis but did not act in an antioxidant
      capacity. The results were confirmed using a Burkitt's lymphoma cell line
      overexpressing transfected bcl-2. The results may be explained by the observation
      that H2O2 was inefficient at inducing apoptosis in these mature B-cell lines.
      Nonapoptotic death induced by H2O2 was not prevented by Bcl-2.

PMID- 9192773
TI  - In vivo efficacy and toxicity of a single-chain immunotoxin targeted to CD40.
AB  - G28-5 sFv-PE40 is a single-chain immunotoxin targeted to CD40, which is highly
      expressed on human hematologic malignancies, including non-Hodgkin's lymphoma, B
      lineage leukemias, multiple myeloma, and Hodgkin's disease, as well as certain
      carcinomas. In vitro analysis showed that this monovalent immunotoxin had a
      binding affinity of 3 nmol/L, within 15-fold of the bivalent parental monoclonal
      antibody. G28-5 sFv-PE40 was stable when incubated in mouse serum at 37 degrees C
      for 6 hours and cleared from the circulation of mice with a half-life of 16.7
      minutes. This immunotoxin was effective in treating human Burkitt's lymphoma
      xenografted SCID mice with complete responses, defined by an asymptomatic
      phenotype for greater than 120 days, obtained at doses of 0.13 to 0.26 mg/kg. The
      efficacy of treatment was dependent on the schedule used, with every three days
      for five injections being the most effective tested. The toxicity of G28-5 sFv
      PE40 was examined in SCID mice, rats, and monkeys, with the maximum tolerated
      dose being 0.48, 1.0, and 1.67 mg/kg, respectively. Comparative immunohistology
      showed that the G28-5 specificity was qualitatively similar between human and
      monkey tissue. In summary, G28-5 sFv-PE40 was effective at inducing complete
      antitumor responses in lymphoma xenografted mice at doses that were well
      tolerated in mice, rats, and monkeys.

PMID- 9192775
TI  - Evaluation of the Revised European-American Lymphoma classification confirms the
      clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin's
      lymphoma.
AB  - The Revised European-American Lymphoma (REAL) classification has been criticized
      for its emphasis on the unproven clinical relevance of immunophenotype. A worse
      prognosis for peripheral T-cell non-Hodgkin's lymphomas (PTCLs) has been
      inconsistently reported in part because the definition of PTCL has been imprecise
      (eg, T-cell-rich B-cell non-Hodgkin's lymphomas [TCRBCLs] have been misdiagnosed
      as PTCLs in the past) and because its correlation with other known prognostic
      factors has not been studied by multivariate analysis. We analyzed six protocols
      from 1984 to 1995 with Working Formulation intermediate grade and immunoblastic
      lymphomas (exclusive of mantle cell) and selected only those cases in which
      immunophenotyping was performed and was conclusive. Of a total of 560 evaluable
      patients, 68 were PTCLs (12%) and the remaining 492 (88%) were B-cell non
      Hodgkin's lymphomas, including 16 TCRBCLs (3% of total). The 5-year failure-free
      survival (FFS) for PTCLs and B-cell large-cell lymphomas (BCLCLs) is 38% and 55%,
      respectively (P < .0001) and the 5-year overall survival (OS) is 39% and 262%,
      respectively (P < .001). The M.D. Anderson prognostic tumor score (MDATS) and
      International Prognostic Index (IPI) for all patients was calculated. With MDATS
      of less than 3 (good prognosis), the 5-year FFS for PTCL and BCLCL is 56% and
      69%, respectively (P = .01), and the 5-year OS is 64% and 77%, respectively (P =
      .06). With MDATS of greater than 2 (poor prognosis), 5-year FFS for PTCL and
      BCLCL is 26% and 38%, respectively (P = .03), and the 5-year OS is 24% and 41%,
      respectively (P = .02). With an IPI of less than 3 (good prognosis), the 5-year
      FFS for PTCL and BCLCL is 49% and 64%, respectively (P = .001), and the 5-year OS
      is 55% and 71%, respectively (P = .013). With an IPI greater than 2 (poor
      prognosis), the 5-year FFS for PTCL and BCLCL is 11% and 35%, respectively (P =
      .044), and the 5-year OS is 10% and 40%, respectively (P = .011). Multivariate
      analysis shows that MDATS, IPI, and T-cell phenotype are totally independent and
      are the most significant predictors of FFS and OS. The 68 PTCLs include 45 PTCLs
      unspecified, 10 Ki-1 anaplastic (ALCL), 8 angioimmunoblastic, and 5 angiocentric
      lymphomas. Angiocentrics were usually refractory (1 of 5 remissions only). ALCL
      rarely relapsed late. We conclude that the immunophenotypic basis of the REAL
      classification is clinically relevant and that, although other prognostic
      features also influence outcome, the T-cell phenotype still remains an
      independent and significant prognostic factor.

PMID- 9192774
TI  - Nonnasal lymphoma expressing the natural killer cell marker CD56: a
      clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.
AB  - Expression of the natural killer (NK) cell antigen CD56 is uncommon among
      lymphomas, and those that do are almost exclusively of non-B-cell lineage and
      show a predilection for the nasal and nasopharyngeal region. This study analyzes
      49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize
      the clinicopathologic spectrum of these rare neoplasms. All patients were
      Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma
      (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including
      25 men and 9 women. They presented with extranodal disease, usually in multiple
      sites. The commonest sites of involvement were skin, upper aerodigestive tract,
      testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%)
      apparently had stage I disease. The neoplastic cells were often pleomorphic, with
      irregular nuclei and granular chromatin, and angiocentric growth was common. The
      characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases
      (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in
      29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5
      months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively.
      (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with
      hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly
      or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic
      granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+
      CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within
      6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled
      those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative
      and both cases were EBV-. One patient was alive with disease at 10 months and one
      was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8)
      included one case each of hepatosplenic gammadelta T-cell lymphoma and S100
      protein+ T-cell lymphoproliferative disease and two cases each of T-chronic
      lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic
      lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5
      months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly
      aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK
      cell leukemia/lymphoma show distinctive clinicopathologic features and a very
      strong association with EBV. Blastoid NK cell lymphoma appears to be a different
      entity and shows no association with EBV.

PMID- 9192776
TI  - Isolation and characterization of transformed human T-cell lines infected by
      Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) is a human lymphotropic virus whose main targets have
      traditionally been described as B lymphocytes and epithelial cells. Here we
      report the isolation and characterization of largely monoclonal transformed human
      T-cell lines infected by EBV. The transformed T cells expressed CD2, CD3, and
      either CD4 or CD8 surface molecules and more generally displayed the phenotype of
      naive T cells with a complete and clonal rearrangement of the T-cell receptor.
      None of the cell lines expressed B cells, natural killer, or myeloid antigens or
      had immunoglobulins genes rearrangement. They grew in the absence of growth
      factor; however, they all secreted interleukin-2 after mitogenic activation.
      Polymerase chain reaction (PCR) analysis showed the presence of EBV DNA in all
      these cell lines. Moreover, Southern blot analysis of one of these cell lines
      shows the presence of circular episomic EBV DNA, and by Northern blot or reverse
      transcriptase-PCR analysis, only the expression of Epstein-Barr nuclear antigen-1
      (EBNA-1) and latent membrane protein-1 (LMP-1) genes was detected. Finally, the
      complete transformed phenotype of this T-cell line was shown by its injection
      into nude or recombination activating gene 2 (RAG2)-deficient mice that led to
      the formation of solid tumors.

PMID- 9192778
TI  - Distribution of ABL and BCR genes in cell nuclei of normal and irradiated
      lymphocytes.
AB  - Using dual-color fluorescence in situ hybridization (FISH) combined with two
      dimensional (2D) image analysis, the locations of ABL and BCR genes in cell
      nuclei were studied. The center of nucleus-to-gene and mutual distances of ABL
      and BCR genes in interphase nuclei of nonstimulated and stimulated lymphocytes as
      well as in lymphocytes stimulated after irradiation were determined. We found
      that, after stimulation, the ABL and BCR genes move towards the membrane, their
      mutual distances increase, and the shortest distance between heterologous ABL and
      BCR genes increases. The distribution of the shortest distances between ABL and
      BCR genes in the G0 phase of lymphocytes corresponds to the theoretical
      distribution calculated by the Monte-Carlo simulation. Interestingly, the
      shortest ABL-BCR distances in G1 and S(G2) nuclei are greater in experiment as
      compared with theory. This result suggests the existence of a certain regularity
      in the gene arrangement in the G1 and S(G2) nuclei that keeps ABL and BCR genes
      at longer than random distances. On the other hand, in about 2% to 8% of
      lymphocytes, the ABL and BCR genes are very close to each other (the distance is
      less than approximately 0.2 to 0.3 microm). For comparison, we studied another
      pair of genes, c-MYC and IgH, that are critical for the induction of t(8;14)
      translocation that occurs in the Burkitt's lymphoma. We found that in about 8% of
      lymphocytes, c-MYC and IgH are very close to each other. Similar results were
      obtained for human fibroblasts. gamma-Radiation leads to substantial changes in
      the chromatin structure of stimulated lymphocytes: ABL and BCR genes are shifted
      to the nuclear center, and mutual ABL-BCR distances become much shorter in the G1
      and S(G2) nuclei. Therefore, we hypothesize that the changes of chromatin
      structure in the irradiated lymphocytes might increase the probability of a
      translocation during G1 and S(G2) stages of the cell cycle. The fact that the
      genes involved in the t(8;14) translocation are also located close together in a
      certain fraction of cells substantiates the hypothesis that physical distance
      plays an important role in the processes leading to the translocations that are
      responsible for oncogenic transformation of cells.

PMID- 9192777
TI  - Engraftment of allogeneic hematopoietic progenitor cells with purine analog
      containing chemotherapy: harnessing graft-versus-leukemia without myeloablative
      therapy.
AB  - The immune-mediated graft-versus-leukemia effect is important to prevent relapse
      after allogeneic progenitor cell transplantation. This process requires
      engraftment of donor immuno-competent cells. The objective of this study was to
      assess the feasibility of achieving engraftment of allogeneic peripheral blood or
      bone marrow progenitor cell after purine analog containing nonmyeloablative
      chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS)
      who were not candidates for a conventional myeloablative therapy because of older
      age or organ dysfunction were eligible. All patients had an HLA-identical or one
      antigen-mismatched related donor. Fifteen patients were treated (13 with acute
      myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71
      years). Twelve patients were either refractory to therapy or beyond first
      relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with
      idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or
      melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine
      at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients
      received allogeneic peripheral blood stem cells and 1 received bone marrow after
      chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of
      cyclosporine and methyl-prednisolone. Treatment was generally well tolerated,
      with only 1 death from multiorgan failure before receiving stem cells. Thirteen
      patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10
      days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of
      20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78
      days). Eight patients achieved complete remissions (bone marrow blasts were < 5%
      with neutrophil recovery and platelet transfusion independence) that lasted a
      median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade
      > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of
      8 patients achieving remission showed > or = 90% donor cells between 14 and 30
      days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90
      days continued to have > or = 80% donor cells. We conclude that purine analog
      containing nonmyeloablative regimens allow engraftment of HLA-compatible
      hematopoietic progenitor cells. This approach permits us to explore the graft
      versus-leukemia effect without the toxicity of myeloablative therapy and warrants
      further study in patients with leukemia who are ineligible for conventional
      transplantation with myeloablative regimens either because of age or concurrent
      medical conditions.

PMID- 9192780
TI  - Isolation and characterization of complement receptor type 1 (CR1) storage
      vesicles from human neutrophils using antibodies to the cytoplasmic tail of CR1.
AB  - Neutrophil (PMN) activation is associated with increased surface expression of
      several membrane proteins that are translocated from intracellular pools.
      Indirect evidence suggests that the intracellular storage pools of complement
      receptor type 1 (CR1) in resting PMN are distinct from traditional granules and
      may be the secretory vesicles in which albumin is also stored, but it is not
      known if this compartment is homogeneous or heterogeneous. To isolate and
      characterize the CR1-containing vesicles, we used antibodies against unique
      sequences in the cytoplasmic tail of CR1. Affinity-purified IgG was used to
      adsorb CR1 storage vesicles from the light membrane fraction (gamma-band) of
      nitrogen cavitates of resting PMN. The immunoadsorbent could quantitatively
      remove the CR1-containing vesicles, whereas control adsorbents with nonimmune IgG
      showed no specific binding of CR1. Immunoblots of specifically isolated vesicles
      also showed enrichment of albumin, decay-accelerating factor, Fc gammaRIII, and
      CR3; whereas HLA class I was not detectable in these vesicles. Enzyme assay of
      specifically isolated vesicles after treatment with Triton X-100 showed that
      these vesicles contained most of the cells' latent alkaline phosphatase. An
      additional population of vesicles containing albumin, but not CR1, and that did
      not bind to anti-CR1 adsorbent was also identified. Immunoelectron microscopy
      showed that the specifically isolated vesicles had mean diameters of 0.086 to 0.1
      microm and stained positive for CR1 and albumin. These results indicate that CR1
      storage vesicles can be isolated with antibodies against the cytoplasmic tail of
      CR1 and show that these vesicles also contain albumin as well as
      glycosylphosphatidyl inositol-anchored proteins. These results are most
      compatible with the hypothesis that CR1-containing vesicles have arisen by
      endocytic retrieval of proteins that had been on the plasma membrane.

PMID- 9192779
TI  - GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase
      promoter.
AB  - Neutrophil elastase (NE) is a serine protease that is transcriptionally regulated
      during early myeloid differentiation. The murine NE (mNE) promoter contains
      functionally important c-Myb, C/EBP, and ets binding sites. Deletion of the ets
      site reduced promoter activity by 90%. Although the ets transcription factor,
      PU.1, bound to this ets site, it only modestly activated the mNE promoter. Here,
      we show that a second transcription factor from myeloid cells-GABP-binds to the
      mNE ets site but strongly activates the mNE promoter. GABP is a heteromeric
      transcription factor complex that consists of GABP alpha, an ets factor, and GABP
      beta, a Notch-related protein. GABP alpha bound to the mNE ets site and, in turn,
      recruited GABP beta to form a transcriptionally active complex. GABP alpha and
      PU.1 competed with each other for binding to the mNE ets site. GABP increased the
      activity of the mNE promoter sevenfold in U937 myeloid cells. GABP cooperated
      with c-Myb and C/EBP alpha to activate the mNE promoter more than 85-fold in
      otherwise nonpermissive, nonhematopoietic NIH 3T3 cells. Thus, GABP binds to the
      crucial mNE promoter ets site and powerfully activates its expression alone and
      in cooperation with the transcription factors c-Myb and C/EBP.

PMID- 9192781
TI  - Pertussis toxin shows distinct early signalling events in platelet-activating
      factor-, leukotriene B4-, and C5a-induced eosinophil homotypic aggregation in
      vitro and recruitment in vivo.
AB  - The present study was performed to investigate the early signalling events
      responsible for eosinophil activation in response to platelet-activating factor
      (PAF), C5a, and leukotriene B4 (LTB4). We evaluated the effect of pertussis toxin
      (PTX) on eosinophil aggregation in vitro and cutaneous eosinophil recruitment in
      vivo. Further studies using the protein kinase inhibitors Ro 31-8220 and
      staurosporine were performed in vitro to assess in more detail the early
      signalling events induced by these three mediators. Our results show that C5a and
      LTB4 signal predominantly or exclusively through a PTX-sensitive G protein that
      is negatively modulated by protein kinase C, possibly at the level of
      phospholipase C-beta. In contrast, PAF activates eosinophils independent of Gi by
      a mechanism that is abolished by Ro 31-8220, a selective protein kinase C
      inhibitor. In addition, these results show for the first time that a receptor
      operated event on the eosinophil is essential for chemoattractant-induced
      eosinophil recruitment in vivo.

PMID- 9192782
TI  - Plasmin is a potent and specific chemoattractant for human peripheral monocytes
      acting via a cyclic guanosine monophosphate-dependent pathway.
AB  - We have previously reported that the serine protease plasmin generated during
      contact activation of human plasma triggers biosynthesis of leukotrienes (LTs) in
      human peripheral monocytes (PMs), but not in polymorphonuclear neutrophils
      (PMNs). We now show that purified plasmin acts as a potent chemoattractant on
      human monocytes, but not on PMNs. Human plasmin or plasminogen activated with
      urokinase, but not active site-blocked plasmin or plasminogen, elicited monocyte
      migration across polycarbonate membranes. Similarly, stimulation of monocytes
      with plasmin, but not with active site-blocked plasmin or plasminogen, induced
      actin polymerization. As assessed by checkerboard analysis, the plasmin-mediated
      monocyte locomotion was a true chemotaxis. The plasmin-induced chemotactic
      response was inhibited by the lysine analog trans-4-(aminomethyl)cyclohexane-1
      carboxylic acid (t-AMCA), which prevents binding of plasmin/ogen to the
      appropriate membrane binding sites. In addition, active site-blocked plasmin
      inhibited monocyte migration triggered by active plasmin. Further, plasmin
      induced monocyte chemotaxis was inhibited by pertussis toxin (PTX) and 1-O
      hexadecyl-2-O-methyl-rac-glycerol (HMG) and chelerythrine, two structurally
      unrelated inhibitors of protein kinase C (PKC). Plasmin, but not active site
      blocked plasmin or plasminogen, triggered formation of cyclic guanosine
      monophosphate (cGMP) in monocytes. LY83583, an inhibitor of soluble guanylyl
      cyclase, inhibited both plasmin-induced cGMP formation and the chemotactic
      response. The latter effect could be antagonized by 8-bromo-cGMP. In addition,
      KT5823 and (Rp)-8-(p-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate
      [(Rp)-8-pCPT-cGMPs], two structurally unrelated inhibitors of cGMP-dependent
      protein kinase, inhibited plasmin-mediated monocyte chemotaxis. Thus, beyond
      being a stimulus for lipid mediator release, plasmin is a potent and specific
      chemoattractant for human monocytes acting via a cGMP-dependent mechanism.
      Therefore, plasmin represents a proinflammatory activator for human monocytes.

PMID- 9192783
TI  - Spectrin St Claude, a splicing mutation of the human alpha-spectrin gene
      associated with severe poikilocytic anemia.
AB  - An alpha-spectrin variant with increased susceptibility to tryptic digestion,
      alpha(II/47), was previously observed in a child with severe, recessively
      inherited, poikilocytic anemia. The molecular basis of this variant, spectrin St
      Claude, has now been identified as a splicing mutation of the alpha-spectrin gene
      due to a T --> G mutation in the 3' acceptor splice site of exon 20. This
      polypyrimidine tract mutation creates a new acceptor splice site, AT --> AG, and
      leads to the production of two novel mRNAs. One mRNA contains a 12 intronic
      nucleotide insertion upstream of exon 20. This insertion introduces a termination
      codon into the reading frame and is predicted to encode a truncated protein (108
      kD) that lacks the nucleation site and thus cannot be assembled in the membrane.
      In the other mRNA, there is in-frame skipping of exon 20, predicting a truncated
      (277 kD) alpha-spectrin chain. The homozygous propositus has only truncated 277
      kD alpha-spectrin chains in his erythrocyte membranes. His heterozygous parents
      are clinically and biochemically normal. This allele was identified in 3% of
      asymptomatic individuals from Benin, Africa.

PMID- 9192784
TI  - Mechanisms of stroke in sickle cell disease: sickle erythrocytes decrease
      cerebral blood flow in rats after nitric oxide synthase inhibition.
AB  - The etiology of stroke in sickle cell disease is unclear, but may involve
      abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered
      vasomotor tone regulation. Therefore, we examined both the adhesion of sickle
      (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood
      flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was
      studied in the rat cerebral microcirculation using either a cranial window for
      direct visualization of infused RBCs or laser Doppler flowmetry (LDF) to measure
      RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs
      had increased adhesion to rat cerebral microvessels compared with control AA-RBCs
      (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with
      LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase
      inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), or the control isomer,
      D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a
      significant decrease in LDF and died within 30 minutes after the RBC infusion (P
      = .0012). In contrast, all control groups completed the experiment with stable
      LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1
      mmol/L) through the cranial window followed by infusion of SS-RBCs. Total
      cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats
      within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is
      critical in maintaining cerebral blood flow in the presence of SS-RBCs in this
      rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain
      microvessels may contribute to cerebral vaso-occlusion either directly, by
      disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

PMID- 9192785
TI  - Cyanocobalamin [c-lactam] inhibits vitamin B12 and causes cytotoxicity in HL60
      cells: methionine protects cells completely.
AB  - The [c-lactam] derivative of cobalamin antagonizes vitamin B12 in vivo.
      Therefore, we investigated its effects in tissue culture to develop a model in
      which to study vitamin B12-deficient hemopoiesis. HL60 cells were cultured in
      medium containing either methionine or L-homocysteine thiolactone, and various
      concentrations of 5-methyltetrahydrofolate or pteroylglutamic acid. In medium
      with L-homocysteine thiolactone, 5-methyltetrahydrofolate, and dialyzed serum,
      cyanocobalamin [c-lactam] caused cell death, reversible by additional vitamin
      B12. Pteroylglutamic acid did not prevent this cytotoxic effect. Methionine
      completely protected cells against cyanocobalamin [c-lactam] for periods of up to
      4 months of culture, irrespective of the folate source. Cyanocobalamin [c-lactam]
      reversibly impaired the incorporation of 5-[14CH3]-tetrahydrofolate and [1-(14)C]
      propionic acid by intact cells, consistent with inhibition of methionine synthase
      and methylmalonyl-CoA mutase. A substantial proportion of 5-[14CH3]
      tetrahydrofolate uptake could not be suppressed by methionine and may, therefore,
      have occurred outside of the methionine synthase pathway. These findings are the
      first indication that cyanocobalamin [c-lactam] antagonizes vitamin B12 in vitro
      and causes cell death from methionine deficiency. The model should be valuable
      for investigating the biochemical pathology of vitamin B12-deficient hemopoiesis.
      The results suggest that methylfolate is not trapped when methionine synthase is
      inhibited in HL60 cells, but they do not disprove the methylfolate trap
      hypothesis as applied to normal blood cells.

PMID- 9192786
TI  - Organization of the human LU gene and molecular basis of the Lu(a)/Lu(b) blood
      group polymorphism.
AB  - The Lutheran (Lu) blood group antigens and the B-cell adhesion molecule (B-CAM)
      epithelial cancer antigen are carried by recently cloned integral glycoproteins
      that belong to the Ig superfamily. We have previously shown that the Lu and B-CAM
      antigens are encoded by the same gene, LU, and that alternative splicing of the
      primary transcript most likely accounts for the presence of both antigens on two
      isoforms that differ by the length of their cytoplasmic tails. In the present
      report, we isolated the human LU gene by cloning a 20-kb HindIII fragment from
      Lu(a - b+) genomic DNA. The LU gene is organized into 15 exons distributed over
      12.5 kb. Alternative splicing of intron 13 generates the 2.5- and 4.0-kb
      transcript spliceoforms encoding the long tail and the short tail Lu
      polypeptides, respectively. Sequencing of the major mRNA species (2.5 kb)
      amplified from human bone marrow, kidney, placenta, and skeletal muscle did not
      suggest the presence of tissue-specific Lu glycoprotein isoforms. The same
      transcription initiation point, located 22 bp upstream from the initiation codon,
      was characterized in several tissues. In agreement with the wide tissue
      distribution of the Lu messengers, the GC-rich proximal 5' flanking region of the
      LU gene does not contain TATA or CAAT boxes, but includes several potential
      binding sites for the ubiquitous Sp1 transcription factor. In addition, the
      distal 5' region, encompassing nucleotides -673 to -764, contains clustered
      binding sequences for the GATA, CACCC, and Ets transcription factors. Analysis of
      the coding sequences amplified from genomic DNA of Lu(a + b-) or Lu(a - b+)
      donors showed a single nucleotide change in exon 3 (A229G) that correlates with
      an Aci I restriction site polymorphism and results in a His77Arg amino-acid
      substitution. Polymerase chain reaction/restriction fragment length polymorphism
      analysis indicated that the A229G mutation is associated with the Lu(a)/Lu(b)
      blood group polymorphism. When expressed in Chinese hamster ovary (CHO) cells, Lu
      cDNAs carrying the A229 or the G229 produced cell surface proteins that reacted
      with anti-Lu(a) or anti-Lu(b) antibodies, respectively, showing that these
      nucleotides specify the Lu(a) and Lu(b) alleles of the Lutheran blood group
      locus. CHO cells expressing recombinant short-tail or long-tail Lu glycoproteins
      reacted as well with anti-Lu as with anti-B-CAM antibodies, providing the
      definitive proof that the Lu blood group and B-CAM antigens are carried by the
      same molecules.

PMID- 9192787
TI  - Apoptosis of late-stage erythroblasts in megaloblastic anemia: association with
      DNA damage and macrocyte production.
AB  - An in vitro model of folate-deficient erythropoiesis has been developed using
      proerythroblasts isolated from the spleens of Friend virus-infected mice fed an
      amino acid-based, folate-free diet. Control proerythroblasts were obtained from
      Friend virus-infected mice fed the same diet plus 2 mg folic acid/kg diet. Our
      previous studies showed that, after 20 to 32 hours of culture in folate-deficient
      medium with 4 U/mL of erythropoietin, the folate-deficient proerythroblasts
      underwent apoptosis, whereas control erythroblasts survived and differentiated
      into reticulocytes over a period of 48 hours. The addition of folic acid or
      thymidine to the folate-deficient medium prevented the apoptosis of the folate
      deficient erythroblasts, thereby implicating decreased thymidylate synthesis as
      the main cause of apoptosis in the folate-deficient erythroblasts. In the study
      reported here, we examined intracellular folate levels, uracil misincorporation
      into DNA, p53 and p21 proteins, and reticulocyte formation in erythroblasts
      cultured in folate-deficient or control medium. In all experiments, the folate
      deficient erythroblasts cultured in folate-deficient medium gave results that
      varied significantly from folate-deficient erythroblasts cultured in control
      medium or control erythroblasts cultured in either folate-deficient or control
      media. Folate-deficient erythroblasts cultured in folate-deficient medium had
      marked decreases in all coenzyme forms of folate that persisted throughout
      culture, increased uracil misincorporation into DNA, persistent accumulations of
      p53 and p21, and decreased reticulocyte production but increased size of
      individual reticulocytes. A model of folate-deficient erythropoiesis based on
      apoptosis of late stage erythroblasts is presented. This model provides
      explanations for the clinical findings in megaloblastic anemia.

PMID- 9192788
TI  - Molecular analysis of eight biochemically unique glucose-6-phosphate
      dehydrogenase variants found in Japan.
AB  - We analyzed the molecular mutations of eight known Japanese glucose-6-phosphate
      dehydrogenase (G6PD) variants with unique biochemical properties. Three of them
      were caused by novel missense mutations: G6PD Musashino by 185 C-->T, G6PD
      Asahikawa by 695 G-->A, and G6PD Kamiube by 1387 C-->T. Predicted amino acid
      substitutions causing asymptomatic variants G6PD Musashino (62 Pro-->Phe) and
      G6PD Kamiube (463 Arg-->Cys) were located in regions near the amino or carboxyl
      end of the polypeptide chain, whereas an amino acid change 232 Cys-->Tyr causing
      a class 1 variant G6PD Asahikawa was located in the region where amino acid
      alterations in some class 1 variants were clustered. The other five variants had
      known missense mutations, namely, G6PD Fukushima, 1246 G-->A, G6PD Morioka, 1339
      G-->A, and G6PD Iwate, G6PD Niigata and G6PD Yamaguchi, 1160 G-->A, which cause
      variants, G6PD Tokyo, G6PD Santiago de Cuba, and G6PD Beverly Hills,
      respectively.

PMID- 9192789
TI  - Familial erythrocytosis associated with a short deletion in the erythropoietin
      receptor gene.
AB  - Familial erythrocytosis (familial polycythemia) inherited as an autosomal
      dominant trait has recently been reported to be associated with mutations in the
      gene encoding the erythropoietin receptor (EpoR) in a small number of families.
      We studied a new kindred with dominantly inherited familial erythrocytosis
      associated with heterozygosity for a deletion of seven nucleotides between
      positions 5985 and 5991 in exon 8 of the EpoR gene, resulting in an EpoR peptide
      that is truncated by 59 amino acids at its C-terminus. A 7-bp direct repeat is
      present in the normal EpoR gene at the site of this mutation, consistent with the
      slipped mispairing model for the generation of short deletions during DNA
      replication. Hypersensitivity to Epo of erythroid progenitors from an affected
      individual was observed in in vitro methylcellulose cultures, as indicated by
      more numerous and larger colonies compared with those of a control subject. To
      study mutant EpoR function, the cDNA encoding the mutant EpoR was synthesized by
      reverse transcription-polymerase chain reaction of peripheral blood RNA from the
      proband and stably tranfected into murine interleukin-3-dependent 32D cells. Epo
      dose-response assays showed that cells expressing the mutant EpoR displayed
      fivefold to 10-fold increased sensitivity to Epo compared with cells expressing
      similar numbers of the wild-type EpoR.

PMID- 9192790
TI  - Prevention of graft-versus-host disease in mice using a suicide gene expressed in
      T lymphocytes.
AB  - Alloreactive T cells present in a bone marrow transplant are responsible for
      graft-versus-host disease (GVHD), but their depletion is associated with impaired
      engraftment, immunosuppression, and loss of the graft-versus-leukemia effect. We
      developed a therapeutic strategy against GVHD based on the selective destruction
      of these alloreactive T cells, while preserving a competent T-cell pool of donor
      origin. We generated transgenic mice expressing in their T lymphocytes the Herpes
      simplex type 1 thymidine kinase (TK) suicide gene that allows the destruction of
      dividing T cells by a ganciclovir treatment. T cells expressing the TK transgene
      were used to generate GVHD in irradiated bone marrow grafted mice. We show that a
      short 7-day ganciclovir treatment, initiated at the time of bone marrow
      transplantation, efficiently prevented GVHD in mice receiving TK-expressing T
      cells. These mice were healthy and had a normal survival. They maintained a T
      cell pool of donor origin that responded normally to in vitro stimulation with
      mitogens or third party alloantigens, but were tolerant to recipient
      alloantigens. Our experimental system provides the proof of concept for a
      therapeutic strategy of GVHD prevention using genetically engineered T cells.

PMID- 9192791
TI  - Persistence of antibody to human parvovirus B19 after allogeneic bone marrow
      transplantation: role of prior recipient immunity.
AB  - Human parvovirus B19 (B19) IgG was studied retrospectively in 66 allogeneic bone
      marrow transplantation (BMT) patients using an enzyme-linked immunosorbent assay.
      Recipient and donor sera had been stored pre-BMT together with sequential sera
      thereafter. Approximately half of donors and recipients had anti-B19 IgG pre-BMT
      and thus the relative contributions of donor and recipient immunity to antibody
      production after transplantation could be assessed. For each patient, a serum
      taken 2 to 3 years after BMT was also tested and the results show that
      persistence of B19 antibody depends on prior recipient (P = .0003) but not on
      donor immunity (P = .8). The findings were similar in both sibling and (VUD) BMT
      volunteer unrelated donor patients. Analysis of sequential post-BMT sera from 41
      of the patients, for whom appropriately timed samples were available, showed
      primary B19 infection in 3 seronegative individuals, whereas 5 others who were
      seropositive before BMT underwent recurrent infection. Sequential results from
      the remaining 33 patients without recent B19 infection showed no evidence for
      donor antibody transfer and confirmed that antibody persistence depends on prior
      recipient immunity. B19 IgG levels decreased variably with time and some patients
      eventually became seronegative. It is concluded that this long-term persistence
      of B19 antibody post-BMT is most probably due to the existence of long-lived
      recipient plasma cells.

PMID- 9192792
TI  - Expression of the T-cell activation antigen, OX-40, identifies alloreactive T
      cells in acute graft-versus-host disease.
AB  - The OX-40 molecule is expressed on the surface of recently activated T
      lymphocytes. The presence of OX-40 on CD4+ T cells was analyzed in a rat haplo
      identical (parental --> F1) bone marrow transplant model of acute graft-versus
      host disease (aGVHD). Increased numbers of activated CD4+ T cells that expressed
      the OX-40 antigen were detected in peripheral blood soon after transplantation
      before the earliest sign of disease. The peak of OX-40 expression occurred 12
      days posttransplantation with a range of 18% to 36% of circulating T cells and
      remained 10-fold above background, never returning to baseline. A slight increase
      in OX-40 expression (range, 1% to 6%) was also detected on peripheral blood
      lymphocytes from control syngeneic F1 --> F1 recipients. OX-40+ T cells were
      isolated from spleen, skin, lymph node, and liver tissue of rats undergoing
      aGVHD, but not in syngeneic transplants. OX-40+ T cells isolated from these
      tissues were of donor origin and were shown to be alloreactive. These data raise
      the possibility of using the OX-40 antibody to detect and deplete selectively the
      T cells that cause aGVHD.

PMID- 9192795
TI  - RH gene structure: reassignment of two exon-exon junctions.

PMID- 9192793
TI  - Blast crisis of chronic myelogenous leukemia in long-lasting systemic lupus
      erythematosus: regression of both diseases after autologous bone marrow
      transplantation.

PMID- 9192794
TI  - Circulating immature cell counts on the harvest day predict the yields of CD34+
      cells collected after granulocyte colony-stimulating factor plus chemotherapy
      induced mobilization of peripheral blood stem cell.

PMID- 9192796
TI  - Use of the polymerase chain reaction-sequence specific oligonucleotide technique
      for the detection of the K1/K2 polymorphism of the Kell blood group system.

PMID- 9192797
TI  - Thrombopoietin in Upshaw-Schulman syndrome.

PMID- 9192798
TI  - Adenoviral vectors in hematology: purging, stem cell gene transfer, or both.

PMID- 9192799
TI  - Acute lymphoblastic leukemia/lymphoblastic lymphoma of natural killer (NK)
      lineage: quest for another NK-lineage neoplasm.

PMID- 9192800
TI  - Enhanced expression of prostate-specific membrane antigen gene in prostate cancer
      as revealed by in situ hybridization.
AB  - Recently, the cDNA encoding a novel candidate for prostate cancer-specific
      antigen, named prostate-specific membrane antigen (PSM), was cloned from the
      LNCaP prostate cancer cell line (R. S. Israeli, C. T. Powell, W. R. Fair, and W.
      D. W. Heston, Cancer Res., 53: 227-230,1993). More recently, they also identified
      an alternatively spliced variant of PSM in normal prostate tissues (S. L. Su, I
      P. Huang, W. R. Fair, C. T. Powell, and W. D. W. Heston, Cancer Res., 55: 1441
      1443, 1995). The cDNA of this variant, named PSM', lacks 266 nucleotides present
      in PSM cDNA, so the transcripts derived from this particular nucleotide sequence
      can be regarded as PSM-specific transcripts. In this study, we investigated the
      expression of PSM-specific transcripts in 15 specimens of prostate cancer
      obtained by needle biopsy using in situ hybridization with a newly developed RNA
      probe. PSM-specific transcripts were detected in most of the carcinoma cells in
      all of the specimens examined, and the level of expression was higher in
      carcinoma cells from hormone-refractory patients than in the cells of those who
      showed a good response to hormonal therapy. In addition, increased expression of
      PSM-specific transcripts was also associated with an increased Gleason score. In
      the normal prostate, on the other hand, PSM-specific transcripts were limited to
      the basal cells of the prostate glands. These results clearly show that
      expression of PSM-specific transcripts is closely associated with malignant
      transformation of the prostate; thus, in situ hybridization for detection of the
      transcripts is useful for the diagnosis of prostate cancer.

PMID- 9192801
TI  - Multidrug resistance protein (MRP) expression in retinoblastoma correlates with
      the rare failure of chemotherapy despite cyclosporine for reversal of P
      glycoprotein.
AB  - Failure of chemotherapy associated with expression of the multidrug resistance
      protein p170 frequently occurs in retinoblastoma (RB). Despite using
      cyclosporine, which inhibits p170 and improves our chemotherapy results, rare
      failures occur. In nonmetastatic primarily enucleated RBs, we show expression of
      p170 in 3 of 18 samples and expression of multidrug resistance protein (MRP), the
      second protein associated with resistance to chemotherapy, in 1 of 18 samples.
      All three RBs that failed chemotherapy without cyclosporine expressed MRP with
      p170. All three RBs that were enucleated immediately when chemotherapy failed
      despite the addition of cyclosporine expressed only MRP. One RB enucleated 2
      years after failing chemotherapy with cyclosporine, despite radiation and salvage
      chemotherapy, expressed both p170 and MRP. Two metastatic RBs that expressed both
      p170 and MRP at diagnosis and at recurrence failed chemotherapy without
      cyclosporine, whereas one metastatic RB that expressed neither protein was cured
      by chemotherapy without cyclosporine. MRP may result in failure of chemotherapy
      despite the elimination of p170-expressing clones by cyclosporine.

PMID- 9192802
TI  - Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma
      of the lung.
AB  - Comparative genomic hybridization was used to screen 25 adenocarcinomas and 25
      squamous cell carcinomas of the lung for chromosomal imbalances. DNA copy number
      decreases common to both entities were observed on chromosomes 1p, 3p, 4q, 5q,
      6q, 8p, 9p, 13q, 18q, and 21q. Similarly, DNA gains were observed for chromosomes
      5p, 8q, 11q13, 16p, 17q, and 19q. Adenocarcinomas showed more frequently DNA
      overrepresentations of chromosome 1q and DNA losses on chromosomes 3q, 9q, 10p,
      and 19, whereas squamous cell carcinomas were characterized by increased
      overrepresentations of chromosome 3q and 12p as well as deletions of 2q. For the
      first time, we used a histogram representation and statistical analysis to
      evaluate the differences between both tumor groups. In particular, the
      overrepresentation of the chromosomal band 1q23 and the deletion at 9q22 were
      significantly associated with adenoid differentiation, whereas the DNA loss of
      chromosomal band 2q36-37 and the overrepresentations at 3q21-22 and 3q24-qter
      were statistically significant markers for the squamous cell type. The study
      strengthens the notion that different tumor subgroups of the respiratory tract
      are characterized by distinct patterns of chromosomal alterations.

PMID- 9192803
TI  - Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both
      familial and sporadic basal cell carcinoma.
AB  - Recently, a human homologue of the Drosophila patched gene, PTCH, was identified
      as a putative tumor suppressor mutated in both hereditary and sporadic basal cell
      carcinomas. Because PTCH controls its own transcription, inactivating mutations
      in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of
      autoregulation. The present study is aimed at evaluating whether deregulation of
      PTCH mRNA expression is a general feature of BCCs of varying histological growth
      pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA
      was overexpressed consistently as determined by in situ hybridization in all of
      the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression
      was found in all of the tumor cells but appeared stronger in the peripheral
      palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells
      or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear
      immunostaining for p53 was found in scattered cells, whereas seven tumors
      completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH
      mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH
      signaling pathway constitutes an early rate-limiting event in BCC development.

PMID- 9192804
TI  - Potent growth inhibitory activity of zidovudine on cultured human breast cancer
      cells and rat mammary tumors.
AB  - Originally designed as an antitumor agent, zidovudine (AZT) has exhibited only
      marginal tumor growth inhibitory activity. Recently, three abstracts have
      described positive clinical outcomes for a small number of patients with advanced
      breast cancer treated with weekly infusions of either methotrexate or cisplatin
      and AZT. Consequently, we conducted a preclinical study of the anti-breast cancer
      and anti-mammary tumor activity of AZT. Here we have demonstrated that AZT,
      alone, has a preferential in vitro and in vivo effect on breast and mammary
      cancer cells. It is 1000 times as potent as an inhibitor of the in vitro growth
      of the human breast cancer cell line MCF-7 (IC50 = 10 +/- 5 nM) than of the
      growth of the T-cell leukemia cell line CEM (IC50 = 14 +/- 2 microM). A novel
      mechanism for this preferential effect on growth is indicated by the 3-4-fold
      increase in production of phosphorylated AZT (mono-, di-, and triphosphate) in
      MCF-7 relative to CEM. We extended these in vitro observations to in vivo studies
      in rats and found that AZT is a potent in vivo inhibitor of the growth of
      methylnitrosourea-induced rat mammary tumors without any apparent toxic effects
      on internal organs. These preclinical results demonstrate, for the first time,
      that AZT has significant anti-breast cancer activity and strongly suggest that
      the clinical usefulness of this drug is worthy of investigation.

PMID- 9192805
TI  - Trioma-based vaccination against B-cell lymphoma confers long-lasting tumor
      immunity.
AB  - A major goal of tumor immunotherapy is the induction of a systemic immune
      response against tumor antigens such as the tumor-specific immunoglobulin
      idiotype (Id) expressed by lymphomas of the B-cell lineage. We describe an
      approach based on specific redirection of the tumor Id toward professional
      antigen-presenting cells (APCs), thereby overcoming the inefficient presentation
      on the parental transformed B cell. Lymphoma cells are fused to a xenogeneic
      hybridoma cell line that secretes an antibody against a surface molecule on APCs.
      Due to preferential assembly between heavy and light chains of antibodies of
      different species-origin, the resulting "trioma" cells produce at high yield a
      bispecific antibody containing the lymphoma Id and the APC-binding arm, which
      redirects the Id to APCs. Processing and presentation of the Id will lead to T
      cell activation. An absolute requirement for inducing a complete tumor protection
      was the immunization with antibody-secreting trioma cells as a cell-based vaccine
      instead of the soluble bispecific antibody. Tumor immunity was specific and long
      lasting. Both CD4+ and CD8+ T cells were necessary for inducing tumor immunity.

PMID- 9192806
TI  - Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal
      tumors.
AB  - The E2F group of transcription factors transactivates genes that promote
      progression through the G1-S transition of the cell cycle. Members of the
      retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function.
      E2F-4, one example of the E2F group, functions as an oncogene when transfected
      into nontransformed cells in vitro. On the other hand, mice that are homozygously
      lacking a normal E2F-1 gene develop cancers, consistent with a tumor-suppressive
      role for this gene. The exact function of E2Fs has thus been unclear; moreover,
      direct involvement of this gene in primary human tumorigenesis has not been
      shown. We, therefore, investigated mutation within the E2F-4 coding region in 16
      primary gastric adenocarcinomas, 12 ulcerative colitis-associated neoplasms, 46
      sporadic colorectal carcinomas, 9 endometrial cancers, and 3 prostatic
      carcinomas. We limited our investigation to the serine repeat within E2F-4,
      reasoning that this tract might be altered in genetically unstable tumors
      (replication error-positive, or RER+). All tumors were RER+, with the exception
      of a control group of 15 RER- sporadic colorectal carcinomas. PCR with
      incorporation of [32P]dCTP was performed using primers flanking the serine
      trinucleotide (AGC) repeat. Twenty-two of 59 gastrointestinal tumors (37%)
      contained E2F-4 mutations; these comprised 5 of 16 gastric tumors (31%), 4 of 12
      ulcerative colitis-associated neoplasms (33%, including 1 dysplastic lesion), and
      13 of 31 sporadic colorectal cancers (42%). No mutation was present in any of the
      endometrial, prostate, or RER- colorectal tumors. Of note, homozygous mutations
      occurred in three cases, and two of seven informative patients showed loss of one
      E2F-4 allele in their tumors. Furthermore, the RER+ sporadic colorectal tumors
      were evaluated at trinucleotide repeats within the genes for N-cadherin and B
      catenin; no tumors demonstrated mutation of these genes. These data suggest that
      E2F-4 is a target of defective DNA repair in these tumors.

PMID- 9192807
TI  - Expression of CD66a (human C-CAM) and other members of the carcinoembryonic
      antigen gene family of adhesion molecules in human colorectal adenomas.
AB  - Among the members of the carcinoembryonic antigen (CEA) family, CD66a (human C
      CAM) and CGM2 (CEA gene family member 2) mRNAs are frequently down-regulated in
      colorectal cancer. In contrast, nonspecific cross-reactive antigen (NCA) mRNA is
      overexpressed in the majority of these carcinomas. In animal models, the rodent
      homologues of CD66a have been shown to act as tumor suppressors, suggesting an
      important role in carcinogenesis. Here we investigate the mRNAs of CD66a, CGM2,
      and NCA in 22 human colorectal adenomas and the respective normal mucosa
      specimens by Northern blots. The expression of both CD66a and CGM2 changed in a
      concomitant fashion. Using oligonucleotides specific for the N-terminal domains,
      two CD66a transcripts 3.9 and 1.5 kb in size were identified. These showed a
      greater than 50% down-regulation in 20 of 22 and 18 of 22 adenomas, respectively.
      Reduction of the CGM2 message was observed in 21 of 22 cases. Complete or near
      complete losses of the CD66a 3.9-kb mRNA and the CGM2 message were found in 13 of
      22 and 15 of 22 of the tumors, respectively. The medians of CD66a and CGM2
      expressions were between 0.3 and 0.0, respectively. The tumor:normal ratio of NCA
      mRNA expression was increased up to 2.4-fold in 11 of 22 adenomas. Altogether,
      these results compare well to the changes reported previously for colorectal
      carcinomas. The high frequency and early appearance of dysregulation of members
      of the carcinoembryonic antigen family during colorectal tumorigenesis suggests
      that these changes may be important for the development of the malignant
      phenotype.

PMID- 9192808
TI  - Absence of G(s)alpha gene mutations in childhood thyroid tumors after Chernobyl
      in contrast to sporadic adult thyroid neoplasia.
AB  - Heterotrimeric G proteins participate in the signal transduction cascade. Adult
      thyroid tumors have been shown to harbor specific point mutations in codons 201
      and 227 of the G(s)alpha subunit of the adenylate cyclase stimulator. This
      protein affects the GDP/GTP turnover and finally results in an enhanced
      activation of G(s) and thus adenylate cyclase. We attempted to find out if
      G(s)alpha gene mutations were present in thyroid tumors of children from Belarus
      after the Chernobyl nuclear accident. Paraffin sections of 20 thyroid tumors were
      used for PCR amplification by oligonucleotide intron primers flanking exons 8 and
      9, encompassing codon 201 and 227, respectively. By direct sequencing of the 274
      bp amplification product, we did not detect any mutations of the G(s)alpha gene
      in codon 201 or 227. In contrast to thyroid neoplasia of adults, G(s)alpha gene
      mutations do not play a role in the development of childhood thyroid tumors after
      the Chernobyl reactor accident.

PMID- 9192809
TI  - Expression of the tumor-associated gene MN: a potential biomarker for human renal
      cell carcinoma.
AB  - MN is a novel cell surface antigen originally detected in human HeLa cells.
      Although it is also expressed in normal gastric mucosa, this antigen was
      previously found to be expressed in cells with a malignant phenotype in certain
      tissues of the female genital tract (cervix and ovary). Using an oligonucleotide
      primer set specific for MN-complimentary DNA, we performed reverse transcription
      PCR assays on RNAs extracted from human cell lines and tissues to evaluate
      whether this marker might be expressed at other sites. RNA libraries extracted
      from normal human heart, lung, kidney, prostate, peripheral blood, brain,
      placenta, and muscle were negative for MN expression. RNAs extracted from liver
      and pancreatic tissue were positive for MN expression. Three of six renal cancer
      cell lines tested revealed MN expression. In addition, 12 of 17 samples of human
      renal cell carcinoma tissue tested positive for MN, all 12 of which were clear
      cell adenocarcinomas. This survey identified a unique association of MN
      expression with renal cell cancers, especially those of the clear cell variety,
      suggesting that MN is a potential marker for the diagnosis, staging, and
      therapeutic monitoring of renal cell carcinoma in humans.

PMID- 9192810
TI  - Overexpression of CDC25A and CDC25B in head and neck cancers.
AB  - The deregulation of several cell cycle-related genes participates in neoplastic
      transformation. Cell cycle progression is driven by cyclin-dependent kinases,
      which are positively regulated by association with cyclins and negatively
      regulated by binding to inhibitory subunits. The activity of cyclin-dependent
      kinases is also regulated by the phosphorylation status, which is controlled by
      the antagonistic action of wee1 kinase and CDC25 phosphatases. Three CDC25 genes
      are present in human cells: CDC25A, CDC25B, and CDC25C. These three genes
      function at different phases of the cell cycle. Whereas CDC25A and CDC25B are
      expressed throughout the cell cycle, with peak expression in G1 for CDC25A and in
      both G1-S-phase and G2 for CDC25B, CDC25C is predominantly expressed in G2.
      Several lines of evidence suggest a role for CDC25s as oncogenes. CDC25A and
      CDC25B cooperate with Ha-ras or loss of Rb1 in the oncogenic transformation of
      rodent fibroblasts. Moreover, they are transcriptional targets of c-myc, and
      CDC25A in particular plays an important role as a mediator of myc functions. On
      the basis of the evidence that CDC25 phosphatases can act as oncogenes, we
      analyzed the expression of CDC25A, CDC25B, and CDC25C genes in 20 squamous cell
      carcinomas of the head and neck by quantitative reverse transcription-PCR. Our
      results show that whereas CDC25C is expressed at a low level with no relevant
      differences between neoplastic tissue and normal mucosa, CDC25A and CDC25B are
      overexpressed in a large fraction of tumors.

PMID- 9192811
TI  - Mutations of the PATCHED gene in several types of sporadic extracutaneous tumors.
AB  - Patients with basal cell nevus syndrome have a high incidence of multiple basal
      cell carcinomas, medulloblastomas, and meningiomas. Because somatic PATCHED
      (PTCH) mutations have been found in sporadic basal cell carcinomas, we have
      screened for PTCH mutations in several types of sporadic extracutaneous tumors.
      We found that 2 of 14 sporadic medulloblastomas bear somatic nonsense mutations
      in one copy of the gene and also deletion of the other copy. In addition, we
      identified missense mutations in PTCH in two of seven breast carcinomas, one of
      nine meningiomas, and one colon cancer cell line. No PTCH gene mutations were
      detected in 10 primary colon carcinomas and eighteen bladder carcinomas.

PMID- 9192812
TI  - Telomerase expression in respiratory epithelium during the multistage
      pathogenesis of lung carcinomas.
AB  - To investigate the role of telomerase in the multistage pathogenesis of lung
      cancer, we examined 205 fresh and archival tissue samples obtained from 40
      patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS)
      without invasion, and 1 without lung carcinoma. We analyzed samples for
      telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat
      amplification protocol assay (131 samples) or by a radioactive in situ
      hybridization method for expression of the RNA component of human telomerase
      (hTR; 74 samples). A subset of samples was assayed by both methods, and the
      correlation was excellent (30 of 36; 83%). With the exception of a carcinoid
      tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to
      strongly positive for both hTR and telomerase activity, except for foci of
      keratinization in squamous cell carcinomas. Telomerase positivity, with weak
      enzyme activity and/or low hTR expression, was present in basal epithelial cells
      of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in
      23% of peripheral lung samples (in epithelium of small bronchi and bronchioles or
      lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia,
      and CIS) were associated with telomerase dysregulation. Dysregulation in
      preneoplasia was manifested in three ways: almost all such lesions expressed hTR,
      although enzyme activity levels were several-fold lower than in the corresponding
      invasive tumors; cells throughout these multilayered processes expressed hTR; and
      intense, focal up-regulation of hTR occurred in CIS foci in the vicinity of
      invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia
      (possible precursor lesions for peripheral adenocarcinomas) were negative. Our
      studies demonstrate that dysregulation of telomerase occurs early in the
      multistage pathogenesis of bronchogenic lung carcinomas and that intense focal
      localized hTR expression in CIS may indicate imminent invasion.

PMID- 9192813
TI  - Characterization of the human homologue of RAD54: a gene located on chromosome
      1p32 at a region of high loss of heterozygosity in breast tumors.
AB  - A search of the Human Genome Sciences database of expressed sequence-tagged DNA
      fragments, for sequences containing homology to known yeast DNA recombination and
      repair genes, yielded a cDNA fragment with high homology to RAD54. Here we
      describe the complete cDNA sequence and the characterization of the genomic locus
      coding for the human homologue of the yeast RAD54 gene (hRAD54). The yeast RAD54
      belongs to the RAD52 epistasis group and appears to be involved in both DNA
      recombination and repair. The hRAD54 gene maps to chromosome 1p32 in a region of
      frequent loss of heterozygosity in breast tumors and encodes a protein of M(r)
      93,000 that displays 52% identity to the yeast RAD54 protein. The hRAD54 protein
      sequence additionally contains all seven of the consensus segments of a
      superfamily of proteins with presumed or proven DNA helicase activity. Mutations
      in genes with consensus helicase homology have been found in cancer-prone
      syndromes such as xeroderma pigmentosum and Bloom syndrome as well as Werner's
      syndrome, in which patients age prematurely, and the X-linked mental retardation
      with alpha-thalassemia syndrome, ATR-X. We have examined the hRAD54 gene in
      several breast tumors and breast tumor cell lines and, although the gene region
      appears to be deleted in several tumors, at present we have found no coding
      sequence mutations.

PMID- 9192814
TI  - Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after
      transfection with the metastasis suppressor gene, KiSS-1.
AB  - Based on the observation that chromosome 1q deletions are not infrequent in late
      stage human breast carcinomas, we tested whether the recently discovered human
      melanoma metastasis suppressor gene, KiSS-1, which maps to chromosome 1q32-q41,
      could suppress metastasis of the human breast carcinoma cell line MDA-MB-435.
      Parental, vector-only transfectants and KiSS-1 transfectant clones were injected
      into the mammary fat pads of athymic nude mice and assessed for tumor growth and
      spontaneous metastasis to regional lymph nodes and lungs. Expression of KiSS-1
      reduced metastatic potential by 95% compared to control cells but did not
      suppress tumorigenicity. Metastasis suppression correlated with a decreased
      clonogenicity in soft (0.3%) and hard (0.9%) agar. Although the overall rate of
      cell adhesion to extracellular matrix components was unaffected, KiSS-1
      transfectants spread on immobilized type-IV collagen more rapidly than did
      control populations. Invasion and motility were unaffected by KiSS-1. Based on
      the predicted structure of the KiSS-1 protein, our results imply a mechanism
      whereby KiSS-1 regulates events downstream of cell-matrix adhesion, perhaps
      involving cytoskeletal reorganization. In addition to its already described role
      in melanoma, our results show that KiSS-1 also functions as a metastasis
      suppressor gene in at least some human breast cancers.

PMID- 9192815
TI  - Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer
      cells grown as multicellular tumor spheroids.
AB  - Tumor cells grown as multicellular spheroids are known to be intrinsically more
      resistant to a large and diverse array of anticancer chemotherapeutic drugs
      compared to the same cells grown as dispersed monolayer cell cultures. Some
      drugs, however, seem relatively insensitive to this multicellular drug
      resistance, e.g., cisplatinum. Whether the cytotoxic effects of Taxol, an
      anticancer drug of growing importance in the treatment of breast and ovarian
      carcinomas, are diminished by multicellular growth conditions is unknown. To
      study this question, we examined the relative sensitivity of a panel of four
      different human ovarian carcinoma cell lines to either Taxol or cisplatinum. Upon
      exposure to Taxol, all the cell lines manifested a relative drug-resistant
      phenotype when grown as multicellular tumor spheroids, compared to the same cells
      grown as sparse monolayer cultures. This multicellular-dependent drug-resistant
      phenotype was not observed when the same cells were exposed to cisplatinum for an
      equivalent length of time. Monolayer but not spheroid cultures exposed to Taxol
      demonstrated an accumulation of cells at G2-M and a sub-G1 apoptotic region. In
      addition, Taxol-induced apoptosis was detected in monolayer conditions but not in
      the spheroid cultures. The relative sensitivity of the monolayer cell cultures
      was associated with a decrease in bcl-X(L) protein levels after Taxol exposure,
      an effect not observed in drug-exposed spheroids. Taken together, these results
      suggest that some aspects of intrinsic Taxol resistance in ovarian carcinoma may
      be due to multicellular-dependent or -associated mechanisms. This raises the
      possibility of using antiadhesive agents to reverse multicellular-dependent Taxol
      resistance in certain circumstances as a potential means of increasing the
      initial efficiency of Taxol therapy against ovarian carcinoma.

PMID- 9192816
TI  - Metal ion-dependent hydrogen peroxide-induced DNA damage is more sequence
      specific than metal specific.
AB  - The frequency of oxidative base damage along the human p53 and PGK1 genes was
      determined at nucleotide resolution by cleaving DNA at oxidized bases with
      endonuclease III and formamidopyrimidine DNA glycosylase and then using the
      ligation-mediated PCR technique to map induced break frequency. Damage was
      induced either in vivo by exposing cultured human male fibroblasts to H2O2 or in
      vitro by exposing purified genomic DNA to H2O2 plus ascorbate in the presence of
      Cu(II), Fe(III), or Cr(VI) metal ions. All four base damage patterns from either
      in vivo or in vitro treatments were nearly identical in both regions of the
      genome. The frequency of base damage varied along the DNA, with guanine being the
      most commonly damaged base. In the Fe(III)-mediated in vitro reactions, single
      stranded breaks were almost completely suppressed by addition of sucrose, which
      facilitated mapping of base damage. The in vitro base damage pattern generated by
      Cr(VI), ascorbate, and H2O2 was similar to that of the other metal ions, with the
      exception of several unique positions; these were heavily damaged only in the
      presence of Cr(VI). Isolated nuclei suffered little oxidative base damage in the
      presence of ascorbate and H2O2, and we conclude that during H2O2 in vivo
      treatment of cells, metal ions (or metal-like ligands) are freed from the
      cytoplasm to migrate into the nucleus and supply the redox cycling ligands
      necessary for oxidative base damage. These data simplify the complexity of H2O2
      induced oxidative damage and mutagenesis studies by demonstrating the commonality
      of damage catalyzed by different transition metal ions and by showing that the
      pattern of H2O2-mediated oxidative base damage is determined almost entirely by
      the primary DNA sequence, with chromatin structure having a limited effect. Our
      data suggest a model for base damage in which DNA-metal ion binding domains can
      equally accommodate a variety of different metal ions and thus are a key factor
      in determining the local probability of DNA damage.

PMID- 9192817
TI  - Toxin-induced increase in survival factor receptors: modulation of the threshold
      for apoptosis.
AB  - The threshold at which toxins induce cell death is thought to directly relate to
      the amount of injury sustained. We show that the threshold at which a cell
      initiates toxin-induced death may vary in response to changes in the trophic
      environment. Treatment of Rat-1 fibroblasts with 50-175 mM dimethylformamide
      (DMF) induced cell death by apoptosis. Addition of insulin-like growth factor 1
      (IGF-1; 100 ng/ml) and/or overexpression of the IGF-1 receptor (IGF-1R)
      attenuated the cytotoxicity of DMF. Furthermore, 95-99% of cells were protected
      from DMF-induced apoptosis if cells were pretreated with platelet-derived growth
      factor (5 ng/ml) for 16 h before treatment with DMF in the presence of IGF-1.
      Platelet-derived growth factor induced the expression of IGF-1R mRNA. The ability
      of cells to proliferate and survive after a 24-h treatment with DMF was
      determined by colony formation; whereas treatment with concentrations of >130 mM
      DMF reduced cellular survival, exposure to concentrations of <130 mM unexpectedly
      increased the colony-forming ability of treated cells when compared to that of
      controls. Treatment of Rat-1 fibroblasts with 75 and 130 mM DMF induced IGF-1R
      mRNA as determined by reverse transcription-PCR analysis. Serum withdrawal also
      transiently increased the expression of IGF-1R mRNA in Rat-1 fibroblasts. These
      results show that cells can actively adapt to pathological and physiological
      stress by up-regulating receptors that provide signals for cellular survival. We
      suggest that the threshold for toxin-induced apoptosis is determined not only by
      the extent of cytotoxic damage but also by the trophic environment and the
      ability of a cell to modulate survival signals that attenuate toxicity.

PMID- 9192818
TI  - Vitamin E inhibits apoptosis, DNA modification, and cancer incidence induced by
      iron-mediated peroxidation in Wistar rat kidney.
AB  - We have developed an experimental model of iron-induced oxidative nephrotoxicity
      and renal cancer. Using this model, the effect of vitamin E, a known antioxidant,
      was investigated. Three-week-old male Wistar rats were fed with vitamin E
      sufficient (control) and vitamin E-supplemented diets throughout the experiment.
      After 1 month of feeding, iron-induced tissue lipid peroxidation, apoptosis, and
      formation of 8-hydroxydeoxyguanosine, a known DNA oxidative modification, were
      observed by cold Schiff staining, in situ labeling method (staining by terminal
      deoxynucleotidyl transferase-mediated nick end labeling), and high-performance
      liquid chromatography with electrochemical detection system, respectively, in the
      groups of rats treated with ferric nitrilotriacetate (Fe-NTA; Fe, 10 mg/kg body
      weight). For the vitamin E intervention study on Fe-NTA-induced renal
      carcinogenesis, two groups of rats fed vitamin E-sufficient and vitamin E
      supplemented diets (30 and 20 rats, respectively) were treated with Fe-NTA (Fe,
      7.5 mg/kg body weight once or twice a week) i.p. for 3 months and observed for 9
      additional months. Five of the vitamin E-sufficient rats died during the first 3
      month period. The results showed that vitamin E could inhibit tissue lipid
      peroxidation, apoptosis, 8-hydroxydeoxyguanosine formation, and the development
      of cancer [11 of 25 rats (44%) for vitamin E-sufficient versus 1 of 20 rats (5%)
      for vitamin E-supplemented rats, respectively]. These studies strongly suggest
      that in Fe-NTA-induced renal cancer, as with certain other types of cancer,
      oxidative stress plays an important role in carcinogenesis, and an antioxidant is
      an effective chemopreventive measure.

PMID- 9192819
TI  - Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice.
AB  - Gene targeting was used to obtain mice defective in the MGMT gene, encoding O6
      methylguanine-DNA methyltransferase [Tsuzuki et al., Carcinogenesis (Lond.), 17:
      1215-1220, 1996]. These MGMT-/- mice were most sensitive to the alkylating
      carcinogen, methylnitrosourea; when varied doses of methylnitrosourea were
      administered to 6-week-old mice and survivals at the 30th day were determined,
      LD50s of MGMT-/- and MGMT+/+ mice were 20 and 240 mg/kg of body weight,
      respectively. MGMT+/- mice were as resistant as MGMT+/+ mice, but some difference
      in survival time was noted when the two genotypes of mice were exposed to a
      relatively high dose of methylnitrosourea. A large number of thymic lymphomas, as
      well as lung adenomas, occurred in MGMT-/- mice exposed to methylnitrosourea at a
      dose of 2.5 mg/kg of body weight. In case of exposure to the same dose of drug,
      no or few tumors occurred in the MGMT+/+ and MGMT+/- mice. It appears that the
      DNA repair methyltransferase protein protected these mice from methylnitrosourea
      induced tumorigenesis.

PMID- 9192820
TI  - Effect of dietary 2(3)-tert-butyl-4-hydroxyanisole on the metabolism and action
      of estradiol and estrone in female CD-1 mice.
AB  - Administration of 0.75% 2(3)-tert-butyl-4-hydroxyanisole (BHA) in AIN-76A diet to
      female CD-1 mice for 3 weeks increased liver microsomal glucuronidation of
      estradiol, estrone, 4-aminophenol, and 4-nitrophenol by 103, 187, 162, and 92%,
      respectively (at pH 7.4). The overall rate of NADPH-dependent metabolism of
      estradiol and estrone by liver microsomes of BHA-treated animals as determined by
      substrate disappearance was increased by 20-40% over that by liver microsomes
      from control animals. The rate of 2-hydroxylation of estradiol and estrone (the
      major metabolic pathway) was increased by 24-38%, the rate of formation of 6alpha
      hydroxyestradiol plus 6beta-hydroxyestradiol was increased by 90-115%, and the
      rate of 6beta-hydroxyestrone formation (a minor metabolite formed in liver
      microsomes from control mice) was increased by approximately 370% over controls.
      In contrast, BHA administration had little or no effect on the liver microsomal
      formation of 4- and 16alpha-hydroxylated estradiol and estrone metabolites.
      Measurable levels of estradiol and estrone were observed in the serum and uterus
      of ovariectomized CD-1 mice at 30 min after a single i.p. injection of 100 or 300
      ng of estradiol or estrone, and these levels were decreased by 30-60% in animals
      fed a 0.75% BHA diet for 18 days prior to the injection of estrogen. Feeding a
      0.75% BHA-supplemented diet to ovariectomized CD-1 mice for 18 days inhibited the
      uterotropic effect of estradiol or estrone (45 or 75 ng/mouse, i.p. once daily
      for 3 days) as compared to the response of animals fed the control diet. BHA
      administration also inhibited estradiol- or estrone-stimulated [3H]thymidine
      incorporation into uterine DNA. In conclusion, feeding a 0.75% BHA-supplemented
      diet to female CD-1 mice for 2-3 weeks increased the activities of liver
      microsomal enzymes that catalyze uridine 5'-diphosphoglucuronic acid-dependent
      glucuronidation and NADPH-dependent oxidation of estradiol and estrone, enhanced
      the in vivo metabolism of these estrogens, and inhibited their uterotropic
      action.

PMID- 9192821
TI  - Alteration in gamma-glutamyl transpeptidase activity and messenger RNA of human
      prostate carcinoma cells by androgen.
AB  - Concentrations of the synthetic androgen R1881 that correspond to physiologically
      relevant concentrations of 5alpha-dihydrotestosterone are capable of altering the
      activity of gamma-glutamyl transpeptidase (GGT) in human prostate carcinoma
      cells. GGT activity of the androgen-responsive prostate cancer cell line LNCaP
      increases >50% above that of the control after a 72-h exposure to 1 nM R1881.
      This elevation in GGT activity occurs as early as 48 h after treatment and is
      maintained for at least 96 h. Loss of glutathione (GSH) from media and
      accumulation of intracellular GSH of cells pretreated with 1 nM R1881 occur at a
      higher rate than in control cells, suggesting that a greater rate of GSH salvage
      is associated with the increased GGT activity. Immunohistochemical staining
      detects an increase in GGT-positive staining in cells treated with 1 nM R1881 for
      72 h. Steady-state mRNA levels for GGT are elevated above those of the control 24
      72 h after treatment. R1881 has no effect on the GGT activity of the androgen
      independent prostate cell line DU145. Growth of LNCaP but not DU145 cells is
      inhibited by 1 nM R1881 compared to that of the control. Inhibitors of GGT
      activity, acivicin and serine-borate, are capable of dampening or blocking the
      effect of R1881 on growth. Growth of LNCaP cells treated with 1 nM R1881 plus 100
      mM glycylglycine, a stimulator of GGT activity, is inhibited to a greater extent
      than the growth of LNCaP cells treated with R1881 alone. These data demonstrate
      that androgens can elevate GGT activity and increase GGT mRNA and protein levels
      in human prostate carcinoma cells. In addition, compounds able to alter GGT
      activity are capable of altering androgen-related growth effects.

PMID- 9192823
TI  - Enhanced uptake of doxorubicin into bronchial carcinoma: beta-glucuronidase
      mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the
      tumor site.
AB  - Lack of tumor selectivity is a severe limitation of cancer chemotherapy.
      Consequently, reducing dose-limiting organ toxicities such as the cardiac
      toxicity of doxorubicin (Dox) is of major clinical relevance. Approaches that
      would facilitate a more tumor-selective anticancer therapy by using nontoxic
      prodrugs that are converted to active anticancer agents at the tumor site have
      been the subject of intensive research. One potential method to overcome the
      cardiac toxicity of Dox is to apply a nontoxic, glucuronide prodrug (HMR 1826)
      from which Dox is released by the action of beta-glucuronidase, an enzyme present
      at high levels in many tumors. Using a recently developed, isolated, perfused
      human lung model, we compared the uptake of Dox into normal lung and lung tumors
      after a 2.5-h lung perfusion with doxorubicin (n = 8) and with the novel
      doxorubicin glucuronide prodrug (n = 8). Dox showed a poor uptake into lung
      tumors as compared with normal lung [mean Dox concentration at the end of
      perfusion, 1.78 +/- 3.11 (median, 0.66) microg/g versus 22.03 +/- 10.4 (median,
      18.5) microg/g; P < 0.001]. However, after perfusion with HMR 1826, the level of
      Dox in tumor tissue was about 7-fold higher than after perfusion with Dox itself
      [14.04 +/- 12.9 (median, 12.9) microg/g versus 1.78 +/- 3.11 (median, 0.66)
      microg/g, P < 0.05, n = 8]. In vitro experiments showed a significantly higher
      beta-glucuronidase expression and activity in the tumors. The extent of in vitro
      cleavage of HMR 1826 by homogenized lung tissue was closely related to the
      content of beta-glucuronidase (r = 0.9834, P < 0.0001). When D-saccharolactone, a
      specific inhibitor of beta-glucuronidase, was added to the perfusate containing
      HMR 1826, no accumulation of Dox in lung tissue was seen. These data indicate
      that the high Dox levels achieved in the tumors with HMR 1826 resulted from
      cleavage of the prodrug by beta-glucuronidase at the tumor site. Thus, the
      problem of poor Dox uptake into lung tumors could be circumvented by applying the
      doxorubicin glucuronide prodrug. Several lines of evidence based on both ex vivo
      and in vitro results indicate that the approach described using a glucuronide
      prodrug may be useful in facilitating more selective delivery of chemotherapy to
      tumors in humans.

PMID- 9192824
TI  - Relationships between the mitochondrial permeability transition and oxidative
      stress during ara-C toxicity.
AB  - The mitochondrial permeability transition and oxidative stress seem to be
      critical alterations in cellular physiology that take place during programmed
      cell death. Failure to undergo apoptosis is associated with drug resistance in
      acute myeloid leukemia and other cancers. Therefore, it is important to establish
      causal relationships between the physiological changes that take place in
      apoptosis, because these are potential targets for novel treatment strategies to
      overcome this form of drug resistance. We describe the use of multilaser flow
      cytometry methods to make correlated measurements of mitochondrial membrane
      potential (MMP), the generation of reactive oxygen intermediates, the cellular
      content of reduced glutathione (GSH), intracellular calcium, and exposure of
      phosphatidylserine on the cell surface. Using these combined methods, we have
      mapped a "death sequence" that occurs after treatment of leukemic blasts with
      clinically relevant concentrations of 1-beta-D-arabinofuranosylcytosine (ara-C).
      Dual labeling of MMP and cellular glutathione content showed that loss of MMP,
      indicative of the permeability transition, took place in cells that were depleted
      of glutathione. The loss of MMP coincided with phosphatidylserine exposure and
      preceded a state of high reactive oxygen generation. Finally, there was an
      increase in intracellular calcium. These results demonstrate that the
      mitochondrial permeability transition takes place during ara-C toxicity but
      suggest that this occurs downstream of the loss of GSH. Thus, oxidative stress
      after ara-C-induced toxicity seems to be a biphasic phenomenon, with the
      permeability transition occurring after a depletion of GSH and preceding a state
      of high reactive oxygen generation.

PMID- 9192825
TI  - Apoptosis primarily accounts for the growth-inhibitory properties of sulindac
      metabolites and involves a mechanism that is independent of cyclooxygenase
      inhibition, cell cycle arrest, and p53 induction.
AB  - Sulindac causes regression of and prevents recurrence of colonic adenomas in
      patients with familial adenomatous polyposis. Although cell cycle arrest and
      apoptosis have been proposed, the mechanism of action is poorly understood. In
      this study, we characterized the growth-inhibitory effects of active metabolites
      of sulindac in cultured colon adenocarcinoma cells by determining the
      contribution of apoptosis and cell cycle arrest and the requirement for
      cyclooxygenase (COX) inhibition and p53 involvement and compared the effects of
      sulindac metabolites with the chemotherapeutic drug, 5-fluorouracil (5-FU). Time
      course and dose-response experiments demonstrated that increased apoptosis
      paralleled the growth-inhibitory effects of the sulfide and sulfone. A
      relationship among a series of nonsteroidal anti-inflammatory drugs was observed
      between potency for growth inhibition and ability to induce apoptosis but not
      potency to inhibit COX. For example, the sulfone was at least 5000-fold less
      potent than the sulfide for inhibiting COX but only 6.5-fold less potent for
      inducing apoptosis. Moreover, the prostaglandin analogue, dimethyl-prostaglandin
      E2, failed to reverse the apoptosis-inducing effects of the sulfide. Sulindac
      metabolites caused G1 cell cycle arrest in proliferating cells but were
      comparably effective in nonproliferating cells. In contrast, 5-FU treatment was
      less effective in nonproliferating cells. Combined treatment with sulindac
      metabolites and 5-FU did not result in an additive apoptotic response. Treatment
      of cells with 5-FU increased p53 protein levels, whereas sulindac metabolites did
      not induce expression. Saos-2 cells, which lack p53, responded to sulindac
      metabolites but not 5-FU. These results show that apoptosis primarily contributes
      to growth inhibition by sulindac metabolites. The biochemical pathway does not
      require COX inhibition or p53 induction and appears to be fundamentally different
      from the apoptotic response to 5-FU.

PMID- 9192822
TI  - The tryphostin AG17 induces apoptosis and inhibition of cdk2 activity in a
      lymphoma cell line that overexpresses bcl-2.
AB  - Tyrphostins are low molecular weight compounds that specifically inhibit protein
      tyrosine kinases. We studied the effects of tyrphostins on OCI-Ly8, a cell line
      derived from a patient with immunoblastic lymphoma that carries the t(14;18)
      translocation and overexpresses the B-cell lymphoma/leukemia-2 gene (bcl-2). To
      test the possibility that tyrphostins induce apoptosis in these cells, overcoming
      the protection rendered by bcl-2, we screened 16 tyrphostins representing
      different families at a concentration of 0.5-50 microM. We found that AG17 was
      the most potent in this regard. Cell cycle analysis demonstrated that AG17
      induces arrest at the G1 phase followed by apoptosis with general reduction of
      the intracellular level of tyrosine-phosphorylated proteins. To further elucidate
      the mechanism of action of AG17, we investigated its effect on some of the key
      proteins that regulate the cell cycle. Bcl-2 and cdk2 protein levels were not
      altered with AG17, whereas cdk2 kinase activity, as well as p21 and p16 protein
      levels, were reduced markedly. These results suggest that the target of AG17 is
      inactivation of cdk2. Because lymphoma cells with the t(14;18) translocation and
      bcl-2 overexpression are resistant to chemotherapy, novel drugs selectively able
      to induce apoptosis in these cells could offer a new approach to the treatment of
      lymphoma patients.

PMID- 9192826
TI  - The effect of interleukin 12 desensitization on the antitumor efficacy of
      recombinant interleukin 12.
AB  - Use of the cytokine interleukin 12 (IL-12) has been shown to enhance the
      rejection of a variety of murine tumors, but preclinical and clinical studies
      have revealed that recombinant IL-12 (rlL-12) can produce severe toxicity. In an
      effort to improve the tolerance and therapeutic effectiveness of this cytokine,
      we investigated the influence of giving a single dose of recombinant murine IL-12
      (rmIL-12) a week prior to daily cytokine administration (predosing) on its toxic
      and antitumor effects. These studies were performed in C3H/HeN mice, in which a
      course of rmIL-12 at standard doses without predosing induced rejection of
      syngeneic K1735 melanomas in 33%, and in A/J mice, in which treatment induced
      rejection of syngeneic B7-1+ SCK (SCK.B7-1) mammary carcinomas in 63%.
      Administration of a predose of rmIL-12 markedly reduced cytokine toxicity in a
      dose-dependent manner and allowed safe administration of up to 8-fold higher
      doses of daily rmIL-12 in C3H/HeN mice and 4-fold higher doses of rmIL-12 in A/J
      mice. Predosing followed by either standard or high daily doses of rmIL-12 did
      not significantly alter most end points of rmIL-12 treatment of K1735 or SCK.B7-1
      tumors (survival, death from tumor, development of protective immunity, and so
      on), but they appeared to attenuate early control of tumorigenesis by rmIL-12.
      Evidence for the latter comes from a shortening of the characteristic rmIL-12
      induced delay in tumor appearance and in the frequent appearance of tumors that
      subsequently regress. However, higher doses appear to produce better therapeutic
      results than standard doses of rmIL-12 after predosing. Predosing severely
      blunted induction of serum IFN-gamma levels by rmIL-12, which probably accounts
      for many of the effects of predosing on rmIL-12 toxicity and efficacy. Thus,
      predosing desensitizes mice to the toxic effects of rIL-12 and allows much higher
      doses to be given but, despite this, it does not improve and, by some criteria,
      it attenuates rIL-12 therapeutic outcome. Our results do not support the use of
      predosing as a way to enhance the effectiveness of rIL-12 in cancer clinical
      trials.

PMID- 9192827
TI  - Bryostatin-1 and IFN-gamma synergize for the expression of the inducible nitric
      oxide synthase gene and for nitric oxide production in murine macrophages.
AB  - Bryostatin-1 (Bryo) is a nontumor-promoting protein kinase C modulator that has
      been shown to have both in vitro and in vivo activity against several murine and
      human tumors. In this study, we investigated the effects of Bryo on nitric oxide
      production, measured as accumulated nitrite (NO2-) in culture supernatant, and
      inducible nitric oxide synthase (iNOS) gene expression in the murine macrophage
      cell line ANA-1. ANA-1 macrophages did not produce NO2- or iNOS mRNA
      constitutively, and very little or no NO2- or iNOS mRNA were detectable upon
      exposure to IFN-gamma. Bryo, although ineffective alone, and IFN-gamma synergized
      to produce high levels of NO2- and iNOS mRNA. The activity of Bryo was evident at
      a concentration of 0.1 ng/ml and reached its maximum at 1 ng/ml. The effects of
      Bryo were time dependent because expression of iNOS mRNA was detectable as early
      as 6 h and increased through 24 h. Analyses of the molecular mechanisms involved
      indicate that Bryo and IFN-gamma mainly regulate iNOS gene expression
      posttranscriptionally through stabilization of iNOS mRNA. Experiments designed to
      investigate the role of tumor necrosis factor alpha (TNF-alpha) in NO2-
      production by Bryo- and IFN-gamma-activated macrophages revealed that ANA-1
      macrophages expressed low levels of TNF-alpha mRNA constitutively that were not
      augmented in the presence of IFN-gamma. However, Bryo alone augmented the TNF
      alpha mRNA expression, which was only slightly increased with the addition of IFN
      gamma. A polyclonal antibody to TNF-alpha was able to completely neutralize TNF
      alpha secreted in either medium or Bryo plus IFN-gamma-treated cultures.
      Neutralizing concentrations of anti-TNF-alpha antibody suppressed the Bryo plus
      IFN-gamma-induced NO2- production approximately by 50%, suggesting that NO2-
      produced by Bryo plus IFN-gamma-treated ANA-1 macrophages may involve both TNF
      alpha-dependent and TNF-alpha-independent mechanisms. Overall, these findings
      provide the first evidence that Bryo and IFN-gamma can synergize for the
      induction of NO2- production as well as iNOS gene expression and show the
      involvement of posttranscriptional mechanisms in the induction of iNOS mRNA.

PMID- 9192828
TI  - A screening for BRCA1 mutations in breast and breast-ovarian cancer families from
      the Stockholm region.
AB  - To identify BRCA1 germ-line mutations in the breast and breast-ovarian cancer
      families in the Stockholm region, a total of 127 families were screened. DNA from
      174 patients from these families were studied using various mutation screening
      techniques, followed by direct DNA sequencing. Mutations were identified in 7 of
      20 families with breast and ovarian cancer and in one family with ovarian cancer
      only, whereas only 1 family of 106 with breast cancer showed a mutation. Thus,
      germ-line mutations in BRCA1 were found in one-third of the families with both
      breast and ovarian cancer, but in only 1% of the breast cancer families. The low
      frequency of germ-line mutations in the site-specific breast cancer families
      means that other genes are likely to segregate in these families.

PMID- 9192829
TI  - The GTPase and Rho GAP domains of p190, a tumor suppressor protein that binds the
      M(r) 120,000 Ras GAP, independently function as anti-Ras tumor suppressors.
AB  - p190 is a Tyr-phosphorylatable G protein of M(r) 190,000 that binds NH2-terminal
      SH2 domains of GAP1, a Ras GAP of M(r) 120,000. p190 contains at least two
      functional domains: a GTPase domain at the NH2 terminus and a GAP domain at the
      COOH terminus that can attenuate signal-transducing activity of three distinct G
      proteins (Rac, Rho, and CDC42). Here, we demonstrate that overexpression of
      either an antisense p190 RNA or a dominant negative mutant (Asn36) of p190 GTPase
      domain (residues 1-251) but not the wild-type p190 GTPase domain is able to
      transform normal NIH/3T3 fibroblasts. Furthermore, overexpression of either the
      wild-type p190 GTPase domain or the COOH-terminal GAP domain can suppress v-Ha
      Ras-induced malignant transformation. These results indicate that p190 contains
      at least two distinct anti-Ras tumor suppressor domains, the GTPase and GAP
      domains, and suggest that one of the mechanisms underlying the suppression of Ras
      transformation by p190 is the attenuation by p190 GAP domain of Rac/Rho/CDC42
      signalings, which are essential for Ras-transformation. In fact, the p190 GAP
      domain alone suppresses the expression of the c-Fos gene, which is mediated by
      Rac/Rho/CDC42 and is required for oncogenicity of Ras.

PMID- 9192830
TI  - K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive
      colorectal cancer patients.
AB  - K-ras gene mutations have been reported as early events in colorectal
      tumorigenesis, but their role in tumor initiation and development is still
      unclear. To analyze and compare K-ras mutational patterns between colorectal
      tissues at different stages of tumor progression in individual patients, 65
      colorectal tissue samples, including carcinoma, adenoma, histologically normal
      mucosa, submucosal muscularis propria, and histologically normal mucosa distant
      from tumor, were obtained from 13 patients with colorectal cancer. In addition,
      normal mucosal tissues obtained from four normal individuals were analyzed. Each
      of the 13 tumors was shown previously to harbor a mutation in either codon 12 or
      13 of the K-ras gene by direct sequencing. These tissues were reanalyzed, using
      the recently established mutant allele enrichment + denaturing gradient gel
      electrophoresis method, which can detect one mutant allele in 10(4)-10(5) normal
      alleles, thus allowing for the analysis of infrequent cells bearing mutations
      against the background of wild-type cells. No K-ras codon 12 mutation was
      detected by this method in the histologically normal mucosal tissues sampled at
      the margin of resection distant from the tumor or in those obtained from four
      normal individuals. On the other hand, these mutations were detected in 9 of 10
      adenoma and 6 of 10 mucosa samples from 10 patients with known K-ras codon 12
      mutations, and also in 2 of 3 carcinoma, 2 of 3 adenoma, and 1 of 3 mucosa
      samples obtained from 3 patients with known K-ras codon 13 mutations. Thus, K-ras
      codon 12 mutations were found to occur with a high frequency (53.8%) in
      histologically normal mucosa adjacent to tumors of patients with K-ras mutation
      positive colorectal cancer, suggesting that they may be useful biomarkers for
      early detection of colorectal cancer. Furthermore, multiple K-ras mutations were
      found in tissues of nearly half of the 13 patients, indicating that distinct
      evolutionary subclones may be involved in the development of tumor in some
      patients with colorectal cancer.

PMID- 9192831
TI  - Quiescence in R3327-G rat prostate tumors after androgen ablation.
AB  - Androgen ablation is frequently used in conjunction with radiotherapy in the
      treatment of high-risk prostate cancer. Androgen ablation-induced cell kinetic
      changes could result in sub-additive (increased quiescence) or supra-additive
      (reduction in repopulation) interactions with radiotherapy. The cell kinetic
      changes were studied in R3327-G Dunning rat prostate tumors grown in vivo using
      double thymidine analogue labeling and flow cytometry, the terminal
      deoxynucleotidyl transferase-mediated nick end labeling assay for apoptosis, and
      measurements of tumor cell numbers. Tumors grown in intact and castrate male rats
      were continuously labeled for various periods of time with chlorodeoxyuridine and
      pulse-labeled with iododeoxyuridine 8 h before tumor removal. Androgen ablation
      resulted in a maximal reduction in labeling index (10 to 1.6%) and an increase in
      potential doubling time (Tpot; 6-42 days) within 3 days, which was related to a
      reduction in growth fraction (65% to <10%). In contrast, the length of S-phase
      was minimally altered (19 to 23 h). The response to androgen ablation involved
      little apoptosis and no necrosis, and Tpot was approximately the same as the
      tumor volume doubling time. Hence, the increase in Tpot was mainly the result of
      a shift to quiescence, and this shift occurred with minimal cell loss. Because
      quiescence is usually associated with radioresistance, these cell kinetic changes
      suggest that a sub-additive interaction may occur for some prostate cancers when
      androgen ablation and irradiation are given together.

PMID- 9192832
TI  - Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas
      correlates with clinical outcome.
AB  - A retrospective immunohistochemical analysis of the adhesion molecule E-cadherin
      (E-CD) was performed in 112 differentiated thyroid carcinomas and 38 synchronous
      and 20 relapse metastases primarily from operations performed at the Medical
      School Hanover between 1982 and 1992. E-CD-specific antibody 5H9 was applied to
      paraffin-embedded tissues. All patients were clinically followed for a maximal
      period of 12 years. Lack of E-CD expression i.e., <5% of tumor cells positive)
      occurred in 18 of 112 (16.1%) cases, whereas the majority showed either low
      (24.1%), medium (35.7%), or high (24.1%) positivity. No difference was found
      between papillary (n = 88) and follicular (n = 24) carcinomas. Univariate
      statistical analysis for survival (Kaplan-Meier) showed that lack of E-CD
      expression (P < 0.024) is an adverse prognostic factor for differentiated thyroid
      carcinomas. The highest significance was seen among patients without lymph node
      involvement at first presentation (pN(0); P = 0.0068) and among females (P =
      0.0033). Multivariate analysis (Cox model) indicated that E-CD staining is an
      independent prognostic factor (corrected risk factor, 3.7; P < 0.03) in addition
      to distant metastasis (pM1) and tumor size. A comparison of E-CD stainings
      between primary tumors and their metastatic lesions showed similar results in
      both synchronous and relapse metastases after therapy. In conclusion, E-CD
      immunostaining is an independent prognostic indicator for differentiated thyroid
      carcinomas. It may help to uncover the small group of patients with
      differentiated thyroid carcinomas carrying a high risk of suffering an
      unfavorable clinical outcome.

PMID- 9192833
TI  - Role of the p53 tumor suppressor gene in the tumorigenicity of Burkitt's lymphoma
      cells.
AB  - Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and, in 60-80%
      of cases, exhibit mutations in the p53 tumor suppressor gene. We examined the
      potential role of the p53 gene in BL tumorigenicity using an in vitro assay that
      measures p53-dependent cell cycle arrest in the G1 phase of the cell cycle and an
      in vivo athymic murine model that detects differences in the tumorigenicity of BL
      cell lines. A highly significant inverse correlation was found between the
      ability of BL cells to arrest in G1 after irradiation and their tumorigenicity in
      athymic mice, consistent with the notion that loss of p53 function is associated
      with increased tumorigenicity. Inactivation of wild-type (wt) p53 function by
      expression of the human papillomavirus E6 protein in the AG876V BL cell line,
      which carries both wt and mutant p53 proteins, rendered the cell line
      significantly more tumorigenic in athymic mice. Transfection of the wt p53 gene
      into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire
      wt p53 function and rendered it less tumorigenic in mice. In addition to
      confirming a role for the loss of p53 function in tumor progression, the data
      demonstrate that wt p53 protein can reduce BL tumorigenicity in vivo.

PMID- 9192834
TI  - Expression and transcriptional regulation of the PD-Ialpha/autotaxin gene in
      neuroblastoma.
AB  - Autotaxin (ATX) is a newly found autocrine tumor cell motility-stimulating
      factor. ATX is a member of the ecto-phosphodiesterase I (PD-I)/ nucleotide
      pyrophosphatase family. PD-Ialpha was found as a brain-type ecto
      phosphodiesterase I/nucleotide pyrophosphatase. ATX and PD-Ialpha are alternative
      splicing products from one gene. ATX stimulates motility of A2058 melanoma cells
      in vitro; however, it has not been known if PD-Ialpha/ATX is expressed in
      naturally occurred human tumors. In this study, we examined the expression of the
      human PD-Ialpha/ATX gene in human neuroblastoma tumor tissues and the motility
      stimulating activity of recombinant ATX on neuroblastoma cells and investigated
      its transcriptional regulatory mechanism in a human neuroblastoma cell line. The
      PD-Ialpha/ATX gene was expressed in the primary tumor tissues from neuroblastoma
      patients to varying degrees. This gene is also expressed in the SMS-KAN
      neuroblastoma cell line. We identified both isoforms, PD-Ialpha and ATX, in these
      tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of
      SMS-KAN cells at low nanomolar concentration. We situated the promoter region,
      which is essential for its transcription in SMS-KAN cells, at -287 to -254
      nucleotides by the promoter activity assay. The gel-shift assay revealed that
      there exists a nuclear protein in SMS-KAN cells that binds this region. These new
      insights about autocrine tumor cell motility-stimulating protein will help us to
      understand the metastatic mechanism of human neuroblastoma.

PMID- 9192835
TI  - The high affinity alphaIIb beta3 integrin is involved in invasion of human
      melanoma cells.
AB  - Integrins play an important role in mediating tumor cell-extracellular matrix
      (ECM) and tumor cell-endothelial cell interactions. The integrin alphaIIb beta3
      (GPIIb-IIIa) is expressed on the surface of platelets in an inactive state and
      requires a conformational change to recognize extracellular matrix proteins such
      as fibrinogen, fibronectin, vitronectin, and others. In this study, we questioned
      whether human melanoma cells express the alphaIIb beta3 integrin. Reverse
      transcription-PCR/Southern blotting, Northern blotting, and dot blotting
      demonstrated the presence of the platelet-type alphaIIb beta3 integrin in human
      melanoma WM 983B, WM 983A, and WM 35 cells. AP-2, a monoclonal antibody (mAb) to
      alphaIIb beta3, positively stained two human melanoma specimens, indicating
      expression of this integrin in vivo. Phorbol 12-myristate 13-acetate and 12(S)
      hydroxyeicosatetraenoic acid, two activators of protein kinase C, stimulated
      adhesion of melanoma cells to immobilized fibronectin and PAC-1, a mAb to
      alphaIIb beta3. PAC-1 specifically recognizes the conformationally active form of
      platelet alphaIIb beta3. Phorbol 12-myristate 13-acetate-stimulated adhesion of
      WM 983B cells to PAC-1 was completely blocked by an RGD peptide, thus providing
      evidence that tumor cell adhesion to PAC-1 is mediated via the alphaIIb beta3
      integrin but not the Fc receptor. Confocal immunofluorescent studies demonstrated
      that fibronectin-adherent melanoma cells possess an intracellularly localized
      pool of high-affinity alphaIIb beta3. Invasion of WM 983B cells through
      fibronectin was stimulated by 12(S)-hydroxyeicosatetraenoic acid, and this
      stimulated invasion was blocked by the mAb PAC-1. The data suggest that melanoma
      cells express the high-affinity alphaIIb beta3 integrin, which is involved in
      tumor invasion.

PMID- 9192836
TI  - Increased facilitated transport of dehydroascorbic acid without changes in sodium
      dependent ascorbate transport in human melanoma cells.
AB  - Many cell types transport vitamin C solely in its oxidized form, dehydroascorbic
      acid, through facilitative glucose transporters. These cells accumulate large
      intracellular concentrations of vitamin C by reducing dehydroascorbic acid to
      ascorbate, a form that is trapped intracellularly. Certain specialized cells can
      transport vitamin C in its reduced form, ascorbate, through a sodium-dependent
      cotransporter. We found that normal human melanocytes and human malignant
      melanoma cells are able to transport vitamin C using both mechanisms. Melanoma
      cell lines transported dehydroascorbic acid at a rate that was at least 10 times
      greater than the rate of transport by melanocytes, whereas both melanoma cells
      and melanocytes transported ascorbate with similar efficiency. Dehydroascorbic
      acid transport was inhibited by deoxyglucose and cytochalasin B, indicating the
      direct participation of facilitative glucose transporters in the transport of
      oxidized vitamin C. Melanoma cells accumulated intracellular vitamin C
      concentrations that were up to 100 times greater than the corresponding
      extracellular dehydroascorbic acid concentrations, whereas intracellular
      accumulation of vitamin C by melanocytes never exceeded the extracellular level
      of dehydroascorbic acid. Melanoma cells transported dehydroascorbic acid through
      at least two different transporters, each with a distinct K(m), a finding that
      agreed well with the presence of several glucose transporter isoforms in these
      cells. Only one kinetic component of ascorbate uptake was identified in both
      melanocytes and melanoma cells, and ascorbate transport was sodium dependent and
      inhibited by ouabain. Both cell types were able to accumulate intracellular
      concentrations of vitamin C that were greater than the extracellular ascorbate
      concentrations. The data indicate that melanoma cells and normal melanocytes
      transport vitamin C using two different transport systems. The transport of
      dehydroascorbic acid is mediated by a facilitated mechanism via glucose
      transporters, whereas transport of ascorbic acid involves a sodium-ascorbate
      cotransporter. The differential capacity of melanoma cells to transport the
      oxidized form of vitamin C reflects the increased expression of facilitative
      transporters associated with the malignant phenotype.

PMID- 9192838
TI  - Identification by shotgun sequencing, genomic organization, and functional
      analysis of a fourth arylsulfatase gene (ARSF) from the Xp22.3 region.
AB  - We recently reported the isolation of two new members of the sulfatase gene
      family, arylsulfatase D (ARSD) and E (ARSE), located approximately 50 kb from
      each other in the Xp22.3 region. Mutation analysis indicated ARSE as the gene
      responsible for X-linked recessive chondrodysplasia punctata. Expression of the
      ARSE gene in COS cells resulted in a heat-labile arylsulfatase activity that was
      inhibited by warfarin. At the same time, we detected the presence of a 1.2-kb
      fragment located at approximately 60 kb from ARSD and ARSE with significant
      homology to these two genes, suggesting the existence of another sulfatase gene,
      arylsulfatase F (ARSF), in Xp22.3. We have used a combined approach of long-range
      genomic sequencing and screening of cDNA libraries to isolate the ARSF gene.
      Expression of the ARSF cDNA in COS cells resulted in a heat-labile arylsulfatase
      activity that is not inhibited by warfarin, supporting our hypothesis that only
      ARSE is specifically inhibited by warfarin and is most likely involved in
      warfarin embryopathy. Genomic analysis revealed that ARSF has an intron/exon
      organization highly similar to those of ARSD and ARSE, which is also shared by
      another Xp22.3 sulfatase gene, ARSC (arylsulfatase C, also known as steroid
      sulfatase), with the splice sites occurring at the same position in all four
      genes. The data obtained from sequence analysis and presented in this paper
      indicate that the ARSC, ARSD, ARSE, and ARSF genes are more similar to each other
      than to other members of the sulfatase gene family, supporting our hypothesis
      that they represent a subfamily of related proteins created through duplication
      events that occurred in an ancestral pseudoautosomal region.

PMID- 9192837
TI  - Avian and murine LR8B and human apolipoprotein E receptor 2: differentially
      spliced products from corresponding genes.
AB  - Apolipoprotein E-mediated lipid metabolism in the central nervous system plays an
      important role in cholesterol and phospholipid homeostasis of this organ, which
      is separated from the circulation by the blood-brain barrier. Moreover, in late
      onset familial Alzheimer disease the frequency of the apolipoprotein E4 allele is
      significantly increased and the apoprotein is localized to extracellular plaques,
      one of the histological hallmarks of this disease. Recently, two distinct novel
      members of the low-density lipoprotein (LDL) receptor family, with the potential
      to bind apolipoprotein E and preferentially expressed in brain, have been
      characterized from human (D. Kim et al., 1996, J. Biol. Chem. 271: 8373-8380) and
      chicken and mouse (S. Novak, et al., 1996, J. Biol. Chem. 271: 11732-11736). The
      human receptor, termed "apolipoprotein E receptor 2," is a seven ligand-binding
      repeat receptor harboring a unique insertion in the cytoplasmic domain of the
      protein. The novel receptor characterized in chicken and mouse was found to have
      eight binding repeats without such a cytoplasmic insertion. Despite the overall
      identity of more than 73%, based upon their structural differences (seven versus
      eight ligand-binding repeats) these receptors have been considered independent
      entities. However, here we demonstrate that both receptors in fact are encoded by
      corresponding genes and that differential splicing gives rise to structurally and
      possibly functionally distinct variants of this brain-specific member of the LDL
      receptor family.

PMID- 9192839
TI  - Genomic structure of the human lysosomal alpha-mannosidase gene (MANB).
AB  - Lysosomal alpha-mannosidase (LAMAN) (EC 3.2.1.24) is an exoglycosidase involved
      in the ordered degradation of N-linked oligosaccharides. Lack of LAMAN activity
      leads to the lysosomal storage disorder alpha-mannosidosis (MIM No. 248500). We
      determined the genomic organization of the human lysosomal alpha-mannosidase gene
      (laman; HGMW-approved symbol MANB) by using oligonucleotide primers designed from
      the human laman cDNA sequence as part of a PCR-based strategy. The gene spanned
      21.5 kb and contained 24 exons. By primer extension analysis, the major
      transcription initiation sites were mapped to positions -309, -196, and -191
      relative to the first in-frame ATG. No CAAT or TATA sequences could be identified
      within 134 bp upstream of the transcription initiation sites, but the 5' flanking
      region contained several GC-rich regions with putative binding sites for the
      transcription factors SP-1, AP-2, and ETF.

PMID- 9192840
TI  - A YAC contig joining the desmocollin and desmoglein loci on human chromosome 18
      and ordering of the desmocollin genes.
AB  - The desmocollins and desmogleins are members of the cadherin family of adhesive
      proteins present in the desmosome type of cell-cell junction. All of the known
      desmoglein and desmocollin isoforms, which have differing tissue and
      developmental distributions, are coded by very closely linked genes at 18q12.1.
      We have previously described YAC clones carrying all three known desmoglein (DSG)
      genes. We have now isolated YAC clones that carry all three known desmocollin
      genes (DSC1, 2, and 3) from two libraries and also isolated clones that join the
      DSC locus to the DSG locus, forming a complete contig for the region. Absence of
      chimeric ends for some of the YACs was confirmed by isolating Vectorette PCR
      products for the YAC ends and mapping the derived DNA sequences back to other
      YACs from CEPH. The whole DSC/DSG gene complex occupies no more than about 700
      kb, and the genes are arranged in the order cen-3'-DSC3-DSC2-DSC1-5'-5'-DSG1-DSG3
      D SG2-3'-tel, so that the two gene clusters are transcribed outward from the
      interlocus region. A P1 clone carrying part of DSC2 and DSC3 confirmed the
      relative orientation of transcription of these two genes. The conservation of
      close genetic linkage may be of trivial importance related to the recent
      duplication of these genes or may be because there is a region within the locus
      that is involved in coordinating the expression of the desmoglein and desmocollin
      genes.

PMID- 9192841
TI  - Construction and characterization of a large-fragment chicken bacterial
      artificial chromosome library.
AB  - A large-insert bacterial artificial chromosome (BAC) library has been constructed
      from male chicken genomic DNA using the new pBeloBAC11 vector. The library was
      prepared in two parts, such that two-thirds of the BAC library (2976 clones) had
      an average insert size of 490 kb (80 clones analyzed), after optimization of
      transformation and HMW DNA size-selection conditions. Fragments of increased
      average size were cloned by coupling a second size strategy using pulsed-field
      gel electrophoresis with optimized electroporation that favored transformation of
      Escherichia coli DH10B cells with very large plasmids. The initial one-third of
      this library (1440 clones) was constructed using the standard protocols and had
      an average insert size of 180 kb (40 clones analyzed). The overall library
      consists, at present, of 4416 clones with a combined insert size average of 390
      kb (ranging from 25 to 725 kb). At least 95% of the BAC clones contain inserts.
      This is partially due to a second color selection performed with respect to white
      colonies, as well as to the optimized ligation conditions used. Based on the
      percentage of clones with inserts and the analysis of insert sizes, we estimate
      this library to represent a 0.8-fold coverage of the chicken genome. Southern
      blot analysis and fluorescence in situ hybridization were performed to confirm
      the identity of the BAC inserts with chicken genomic DNA. Analysis of large
      chicken BAC inserts showed that they were stably propagated for at least 120 cell
      generations. The results indicate that the BAC system is able to carry stably
      very large genomic fragments of chicken DNA, this system translating into a
      powerful tool for physical mapping and positional cloning of the chicken genome.

PMID- 9192842
TI  - Genomic structure and chromosomal localization of the novel ETS factor, PE-2
      (ERF).
AB  - The members of the ETS family of transcription factors are grouped because they
      share a highly conserved DNA binding domain. These factors are involved in growth
      factor pathways and regulate both proliferation and differentiation. To identify
      ETS factors that may be involved in early hematopoietic progenitor regulation, we
      isolated a novel member of the ETS family by reverse transcriptase-PCR of the
      conserved DNA binding domain using degenerate oligonucleotides. This gene directs
      the synthesis of a 2704-nucleotide transcript whose largest open reading frame
      encodes a 548-amino-acid protein. Northern blot analysis reveals ubiquitous
      expression in all human tissues and cell lines tested, with highest levels in the
      testis, ovary, pancreas, and heart. Comparison of this gene with the available
      databases reveals very significant homology to the ETS factor PE-1 and probable
      near-identity with the recently cloned factor ERF. The PE-2 gene is composed of
      four exons spanning over 9 kb of genomic DNA. Sequence analysis of the promoter
      region reveals a GC-rich sequence without a TATA motif and with putative binding
      motifs for CREB, c-myb, and AP-1 factors. Using mouse-human somatic hybrids and
      FISH analysis, the PE-2 gene is localized to human chromosome 19q13.2, a region
      involved in translocations and deletions in leukemias and several solid tumors,
      suggesting that this novel ETS factor may play a role in carcinogenesis.

PMID- 9192843
TI  - Monoallelic expression of human PEG1/MEST is paralleled by parent-specific
      methylation in fetuses.
AB  - We have isolated the human PEG1/MEST gene and have investigated its imprinting
      status and parental-specific methylation. FISH mapping assigned the gene to
      chromosome 7q32, and homologous sequences were identified on the short arm of
      human chromosomes 3 and 5. Through the use of a newly identified intragenic
      polymorphism, expression analysis revealed that PEG1/MEST is monoallelically
      transcribed in all fetal tissues examined. In two informative cases, expression
      was shown to be confined to the paternally derived allele. In contrast to the
      monoallelic expression observed in fetal tissues, biallelic expression was
      evident in adult blood lymphocytes. Biallelic expression in blood is supported by
      the demonstration of PEG1/MEST transcripts in a lymphoblastoid cell line with
      maternal uniparental disomy 7. The human PEG1/MEST gene spans a genomic region of
      approximately 13 kb. Sequence analysis of the 5' region of PEG1/MEST revealed the
      existence of a 620-bp-long CpG island that extends from the putative promoter
      region into intron 1. We demonstrate that this CpG island is methylated in a
      parent-of-origin-specific manner. All MspI/HpaII sites were unmethylated on the
      active paternal allele but methylated on the inactive maternal one.

PMID- 9192844
TI  - Identification, characterization, and precise mapping of a human gene encoding a
      novel membrane-spanning protein from the 22q11 region deleted in velo-cardio
      facial syndrome.
AB  - Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are characterized
      by a wide spectrum of phenotypes including cleft palate, conotruncal heart
      defects, and facial dysmorphology. Hemizygosity for a portion of chromosome 22q11
      has been detected in 80-85% of VCFS/DGS patients. Using a cDNA selection
      protocol, we have identified a new gene, TMVCF (transmembrane protein deleted in
      VCFS), which maps to the deleted interval. The genomic locus is positioned
      between polymorphic markers D22S944 and D22S941. TMVCF encodes a small protein of
      219 amino acids that is predicted to contain two membrane-spanning domains. TMVCF
      is expressed abundantly in human adult lung, heart, and skeletal muscle, and
      transcripts can be detected at least as early as Day 9 of mouse development.

PMID- 9192845
TI  - Comparison of the breakpoint regions of ELE1 and RET genes involved in the
      generation of RET/PTC3 oncogene in sporadic and in radiation-associated papillary
      thyroid carcinomas.
AB  - The RET/PTC3 oncogene is an activated form of the RET protooncogene, which is
      frequently rearranged in papillary thyroid carcinoma. RET/PTC3 results from a
      structural rearrangement between the ELE1 and the RET genes, and it has been
      observed in both sporadic and radiation-associated post-Chernobyl tumors. To
      understand the molecular basis that predisposes RET and ELE1 genes to be
      recurrent targets of "illegitimate" recombination, we examined the genomic
      regions containing the ELE1/RET breakpoints of six sporadic and three post
      Chernobyl tumors in two papillary carcinomas of different origins. Our data
      indicated, in both genes, a clustering of the breakpoints in regions designated
      ELE1-bcr (1.8 kb) and RET-bcr (1.9 kb). Notably, in all sporadic tumors and in
      one post-Chernobyl tumor the ELE1/RET recombination corresponded with short
      sequences of homology (3-7 nt) between the two rearranging genes. In addition, we
      observed an interesting distribution of the post-Chernobyl breakpoints in ELE1
      bcr located within an Alu element, or in between two close Alu elements, and
      always in A+T-rich regions.

PMID- 9192846
TI  - The reticulocalbin gene maps to the WAGR region in human and to the Small eye
      Harwell deletion in mouse.
AB  - We describe the localization of the gene encoding reticulocalbin, a Ca2+-binding
      protein of the endoplasmic reticulum, on human chromosome 11p13 midway between
      the WT1 and the PAX6 genes and show that it is hemizygously deleted in WAGR
      individuals. The mouse reticulocalbin gene is also shown to map to the region of
      conserved synteny on mouse chromosome 2 and to be deleted in the Small eye
      Harwell (SeyH) mutation. Loss of the reticulocalbin gene could contribute to the
      early lethality of SeyH and SeyDey homozygotes.

PMID- 9192847
TI  - Identification of two novel isoforms of the ZNF162 gene: a growing family of
      signal transduction and activator of RNA proteins.
AB  - By differential screening of a cDNA library obtained from a GM-CSF-dependent
      human myeloid leukemia cell line (GF-D8), we identified two novel isoforms of the
      recently described ZNF162 gene, which is apparently linked to multiple endocrine
      neoplasia type 1. The shorter of these new isoforms, called B3, presents an open
      reading frame (ORF) of 1713 bp coding for 571 amino acids. Its nucleotide
      sequence is homologous to the cDNA coding for the ABCDF isoform of ZNF162, except
      for a 4-nucleotide insertion that results in a frame shift of the ORF starting
      from nucleotide 1725 of the ZNF162 sequence. As a consequence, the predicted
      translation product of B3 contains the consensus sequence of the A motif (G-X-X-X
      X-G-K-S) of the "ATP/ GTP binding site," which is characteristic of several
      protein families including protein kinases. Moreover, B3 shows the use of a
      different stop codon and contains a different tyrosine-rich COOH terminus. The
      longer isoform, called B4, differs from the ABCDEF isoform of ZNF162 by the
      insertion, at position 2137, of 383 nucleotides leading to a different, proline
      rich COOH terminus. The complex transcription pattern of the ZNF162 gene is
      characterized by four transcripts, of approximately 3.9, 3.7, 3.2, and 2.9 kb, in
      GF-D8 cells. The 3.7- and 2.9-kb transcripts are expressed in resting GF-D8
      cells. Upon stimulation with GM-CSF the expression of these mRNAs is up-regulated
      in parallel with the induction of two additional transcripts of 3.9 and 3.2 kb.
      The same pattern of expression has also been observed in freshly isolated myeloid
      leukemia cells and normal CD34+ stem cells. In light of these data, and since GM
      CSF is known to stimulate signal transduction pathways, it becomes relevant that
      all the different isoforms of ZNF162 contain the KH module, which is a sequence
      motif present in proteins playing a major role in regulating cellular RNA
      metabolism. A search for functional domains demonstrates that ZNF162 belongs to a
      new and growing family of genes dubbed STAR (signal transduction and activator of
      RNA) proteins that are thought to play a downstream role in cell signaling and
      also in RNA binding. The mammalian members include Sam68, which is a target of
      Src, Fyn, and Grb2, and the newly cloned mouse quaking proteins (qkI) necessary
      in early embryogenesis and myelination. Moreover, since ZNF162 is highly
      conserved from yeast to humans, it implies that this new pathway has a
      significant function.

PMID- 9192848
TI  - A novel tandem repeat sequence located on human chromosome 4p: isolation and
      characterization.
AB  - In an effort to analyze the genomic region of the distal half of human chromosome
      4p, to where Huntington disease and other diseases have been mapped, we have
      isolated the cosmid clone (CRS447) that was likely to contain a region with
      specific repeat sequences. Clone CRS447 was subjected to detailed analysis,
      including chromosome mapping, restriction mapping, and DNA sequencing. Chromosome
      mapping by both a human-CHO hybrid cell panel and FISH revealed that CRS447 was
      predominantly located in the 4p15.1-15.3 region. CRS447 was shown to consist of
      tandem repeats of 4.7-kb units present on chromosome 4p. A single EcoRI unit was
      subcloned (pRS447), and the complete sequence was determined as 4752 nucleotides.
      When pRS447 was used as a probe, the number of copies of this repeat per haploid
      genome was estimated to be 50-70. Sequence analysis revealed that it contained
      two internal CA repeats and one putative ORF. Database search established that
      this sequence was unreported. However, two homologous STS markers were found in
      the database. We concluded that CRS447/pRS447 is a novel tandem repeat sequence
      that is mainly specific to human chromosome 4p.

PMID- 9192849
TI  - Genomic organization and chromosomal localization of a member of the MAP kinase
      phosphatase gene family to human chromosome 11p15.5 and a pseudogene to 10q11.2.
AB  - Mitogen-activated protein kinase phosphatases (MKPs) play a central role in a
      variety of signaling pathways. We recently described a novel murine MKP, M3/6,
      which is uniquely specific for c-Jun N-terminal kinase/stress-activated protein
      kinase and p38 kinase. Here we report the localization of the human orthologue of
      this gene, HB5, to within 150 kb of H19 on human chromosome 11p15.5. The gene
      consists of six exons. Two of the introns in HB5 are not found in other genes of
      this family, suggesting an evolutionary split between MKPs displaying specificity
      toward different MAP kinases. An intronless pseudogene is present on chromosome
      10q11.2. Although 11p15.5 is an imprinted region, HB5 is almost entirely
      unmethylated on both alleles in lymphocytes. Chromosome 11p15 has been implicated
      in the development of a number of tumor types, including lung, a tissue known to
      express this gene. Loss of heterozygosity was found in one of eight informative
      lung tumors studied.

PMID- 9192850
TI  - Transcript mapping in a 46-kb sequenced region at the core of 12q13.3
      amplification in human cancers.
AB  - We used a combination of sequence analysis and exon trapping in an effort to
      determine the complete transcript map for a cosmid (6E5) derived from 12q13.3, a
      region of DNA sequence amplification in human cancers. This cosmid, previously
      known to contain three genes (CDK4, SAS, and OS9), was sequenced, and that
      information was used for computer-assisted analysis. In addition, 6E5 was
      subjected to both internal and 3'-terminal exon-trapping protocols, and the
      results of these studies were used to guide cDNA cloning experiments. These
      studies demonstrate that this cosmid is derived from a remarkably gene-dense
      region and add two new transcripts (KIAA0167 and 6E5.2) to the list of sequences
      that are expressed in tumors bearing amplification of this region.

PMID- 9192851
TI  - Human dishevelled genes constitute a DHR-containing multigene family.
AB  - Three human genes encoding proteins homologous to Drosophila Dishevelled protein
      were cloned and characterized. Amino acid similarity between the different
      Dishevelled proteins is concentrated in three highly conserved regions. Two of
      these regions do not exhibit significant sequence similarity with other known
      proteins; the third is similar to the discs-large homology region, which was
      first found in a Drosophila Discs-large tumor suppressor protein (also known as
      GLGF or PDZ domain). We produced antibodies against human Dishevelled-2 and
      demonstrated that it is a phosphoprotein and can be detected in all cell lines
      and human embryonic tissues examined. Indirect immunofluorescence indicates that
      it is found throughout the cytoplasm. Our results indicate that the human
      dishevelled genes constitute a multigene family and that Dishevelled proteins are
      highly conserved among metazoans.

PMID- 9192852
TI  - Characterization of the human gene encoding the type I alpha and type I beta cGMP
      dependent protein kinase (PRKG1).
AB  - The type I cGMP-dependent protein kinase (cGK) has been shown to play a crucial
      role in the relaxation of vascular smooth muscle by lowering the intracellular
      level of calcium. Two isoforms of type I cGK have been described, type I alpha
      and type I beta, differing only in their N-terminal parts. This report describes
      the cloning of the gene PRKG1 encoding both human type I cGK isoforms. PRKG1 is a
      single-copy gene consisting of 19 exons encompassing at least 220 kb. Several of
      the splice sites previously observed in the Drosophila melanogaster DG2 gene have
      been conserved in PRKG1, and these conserved splice sites correlated well with
      the boundaries between several of the previously proposed functional domains of
      type I cGK. The first two exons of the type I cGK gene were shown to encode the
      type I alpha- and type I beta-specific parts of the cGK. Using 5'-rapid
      amplification of cDNA ends, potential sites for transcription initiation were
      identified 5' upstream of both these exons. Northern blot analyses demonstrated
      distinct patterns of expression of the isoforms of type I alpha and I beta cGK in
      different human tissues.

PMID- 9192853
TI  - Characterization of the rhesus monkey galactocerebrosidase (GALC) cDNA and gene
      and identification of the mutation causing globoid cell leukodystrophy (Krabbe
      disease) in this primate.
AB  - Krabbe disease or globoid cell leukodystrophy (GLD) is a severe lysosomal
      disorder resulting from the deficiency of galactocerebrosidase (GALC) activity.
      This deficiency results in the insufficient catabolism of several galactolipids
      that are important in the production of normal myelin. Since the cloning of the
      human GALC cDNA and gene many disease-causing and polymorphic changes have been
      identified. This autosomal recessive disease has been reported to occur in
      several animal species, and recently the murine and canine GALC genes have been
      cloned. We now describe the cloning of the GALC cDNA and gene from the rhesus
      monkey and the identification of the mutation causing GLD in this species. The
      nucleotide sequence of the coding region and the gene organization were nearly
      identical to human. The deduced amino acid sequence of the monkey GALC was
      compared to the human, dog, and mouse, and it was found to be 97, 87, and 83%
      identical, respectively. The mutation causing GLD in the rhesus monkey is a
      deletion of AC corresponding to cDNA positions 387 and 388 in exon 4. This
      results in a frame shift and a stop codon after 46 nucleotides. A rapid method to
      detect this mutation was developed, and when 45 monkeys from this colony were
      tested, 22 were found to be carriers. The availability of this nonhuman primate
      model of GLD will provide unique opportunities to evaluate treatment for this
      severe disease.

PMID- 9192854
TI  - The human HNP36 gene is localized to chromosome 11q13 and produces alternative
      transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I)
      syndrome.
AB  - Multiple endocrine neoplasia, type 1 (MEN I), is an autosomal dominant syndrome
      of selected endocrine neoplasms whose causative gene, a suspected tumor
      suppressor, has been localized to chromosome 11q13, but has not been identified.
      Recently, the HNP36 cDNA was identified as a novel growth factor responsive gene
      of undetermined biological function that is expressed in the pituitary and
      parathyroid glands. In studies seeking the function of the HNP36 gene product,
      the gene was localized by fluorescence in situ hybridization within the 11q13
      segment. Further analysis of radiation-reduced hybrid DNAs and chromosome 11
      specific YAC clones established that the HNP36 gene is within 80 kb of D11S913, a
      marker tightly linked to the MEN1 gene. Consequently, the HNP36 gene was studied
      as a candidate for the MEN1 gene. The human HNP36 gene was cloned and determined
      to consist of 12 exons. Expression of the HNP36 gene from pituitary and
      parathyroid tissue and four patient tumors or lymphoblasts was confirmed by RT
      PCR amplification of the coding sequences, and HNP36 transcripts were analyzed
      for mutations. All tissues expressed three HNP36 gene transcripts that result
      from alternative splicing and appear to encode related, but distinct, proteins.
      However, DNA sequence determination of the RT-PCR products from MEN I-associated
      tumors found no deletions and identified a single nucleotide difference that may
      be a polymorphism. Thus, mutations in the coding segments of the HNP36 gene are
      not the cause of the MEN I syndrome. Nevertheless, the assignment of the HNP36
      gene to 11q13 and identification of new potential gene products provides a novel
      growth-regulated genetic candidate for other disorders whose genes map to this
      locus.

PMID- 9192855
TI  - Human cholecystokinin type A receptor gene: cytogenetic localization, physical
      mapping, and identification of two missense variants in patients with obesity and
      non-insulin-dependent diabetes mellitus (NIDDM).
AB  - The human CCKAR gene was previously mapped to chromosome 4 using a panel of
      human/hamster somatic cell hybrids. We now report the cytogenetic and physical
      localization of the CCKAR gene. Using fluorescence in situ hybridization, we
      determined that CCKAR maps to 4p15.1-p15.2. On the physical map, CCKAR was
      adjacent to the marker AFMa283yh5, between AFMb355ya5 and WI-4086. A simple
      sequence repeat (D4S391) with high heterozygosity was found in the database, and
      CCKAR and this genetic marker were colocalized on two YACs (933D9 and 928A5). We
      also characterized the genomic structure and determined the exon-intron
      boundaries of the gene. This provided the opportunity to screen the gene in
      patients with non-insulin-dependent diabetes mellitus and/or obesity for single
      nucleotide changes using a single-strand conformational polymorphism strategy.
      Five sequence variants were identified in the coding sequence of the gene,
      including two missense variants (G21R and V365I). The results of these studies
      provide (1) precise genetic and physical mapping data, (2) exon-intron sequences
      for single nucleotide analysis, and (3) identification of two missense mutations
      in the CCKAR gene. The contribution of these CCKAR variants to normal physiology,
      to obesity, and to diabetes can now be evaluated.

PMID- 9192856
TI  - The NNP-1 gene (D21S2056E), which encodes a novel nuclear protein, maps in close
      proximity to the cystatin B gene within the EPM1 and APECED critical region on
      21q22.3.
AB  - We have cloned and molecularly characterized a novel human cDNA that encodes a
      protein of about 52 kDa that was shown by immunocytochemistry to have a nuclear
      localization. Northern blot analysis of a variety of human tissues revealed that
      the gene for this novel nuclear protein, designated NNP-1 (HGMW-approved symbol
      D21S2056E), is ubiquitously expressed as a 2.0-kb transcript. The NNP-1 protein
      displays significant sequence similarity to the C47E12.7 protein of
      Caenorhabditis elegans (38% identity and 58% similarity) and the YD78 protein of
      Saccharomyces cerevisiae (36% identity and 54% similarity). The human NNP-1 gene
      was mapped to a 15-kb DNA interval on chromosome 21q22.3, close to markers
      D21S1459 and D21S1953, that is 25 kb distal to the gene encoding cystatin B.
      Finally, an as-yet unknown gene that is highly related to NNP-1 was found
      proximal to the gene encoding cystatin B, near marker D21S1458, which is
      approximately 75 kb centromeric to the NNP-1 gene.

PMID- 9192858
TI  - Refined genetic location of the chromosome 2p-linked progressive muscular
      dystrophy gene.
AB  - Autosomal recessive progressive muscular dystrophies may be clinically
      subclassified into limb-girdle muscular dystrophy (LGMD) and distal myopathy
      (DM), each clinical form being genetically heterogeneous. Genes for LGMD type 2B
      and Miyoshi myopathy (a form of DM) have been mapped to essentially the same
      region on chromosome 2p. We described recently a large inbred family with
      autosomal recessive muscular dystrophy in which the LGMD and the DM phenotypes
      were manifested in separate affected members, and we assigned the gene for this
      condition to the same locus as in LGMD2B and Miyoshi myopathy. Here we report
      extended haplotypes in this family generated from 15 markers located at the
      region of interest on chromosome 2p13. Key recombinants allowed us to reduce
      further the candidate region for this polymorphic condition and defined the loci
      D2S327 and D2S2111 as the most likely boundaries of the mutant gene.

PMID- 9192857
TI  - Mammalian Rh/T2/S-glycoprotein ribonuclease family genes: cloning of a human
      member located in a region of chromosome 6 (6q27) frequently deleted in human
      malignancies.
AB  - We describe the cloning of a novel human gene belonging to the Rh/T2/S
      glycoprotein class of extracellular ribonucleases. This gene is present in a
      single copy in the human genome and has been mapped to 6q27, a region of the
      human genome prone to rearrangements associated with several human malignancies.
      The predicted open reading frame of the human cDNA encodes a protein of 191 amino
      acids, and the pattern of expression is ubiquitous. Some of the sequence features
      of this gene, in particular those corresponding to the bipartite RNase motif of
      the active site, are perfectly conserved between distant species such as human
      and the plant Lycopersicon esculentum. No mammalian homologues have been
      described so far, and this report presents for the first time both the human and
      the mouse sequences of the corresponding members of this class of highly
      conserved extracellular ribonucleases.

PMID- 9192859
TI  - Characterization of human SHC p66 cDNA and its processed pseudogene mapping to
      Xq12-q13.1.
AB  - SHC is an adapter protein in the Ras-MAPkinase pathway that is involved in the
      regulation of cell growth and differentiation. The p46 and p52 isoforms are
      thought to be produced by the use of two alternative translation initiation sites
      in a 3.4-kb transcript from the SHCA gene, which maps to chromosome 1q21. The p66
      isoform could be encoded by a different 3.8- or 2.8-kb transcript of the same
      gene or alternatively by a SHC-related gene. To characterize other putative genes
      coding for SHC-like proteins, primers from the 3' UTR of the SHCA gene were used
      to screen a yeast artificial chromosome (YAC) library by polymerase chain
      reaction (PCR). Two YAC clones, 20D11B and 36D1D, were isolated and used as
      probes for fluorescence in situ hybridization analysis. Both these probes
      hybridized to chromosome Xq12-q13.1. This novel SHC-related sequence was
      characterized by direct sequencing of vectorette library PCR products produced
      from clone 20D11B. A transcript of 3.2 kb that was 85% identical to the mouse Shc
      cDNA encoding the p66 isoform was identified. Sequence analysis demonstrated the
      presence of multiple stop codons identifying this isoform of SHC as a processed
      pseudogene. Using primers designed on the basis of the nucleotide sequence of the
      pseudogene, we have now amplified and sequenced a human cDNA that encodes the SHC
      p66 protein. Thus, we have characterized the human SHC p66 isoform cDNA and
      identified a processed SHC pseudogene that maps to chromosome Xq12-q13.1.

PMID- 9192860
TI  - Cloning of human chromosome 17-specific cDNAs using representational difference
      analysis and human-mouse hybrid cells.
AB  - We employed cDNA representational difference analysis (RDA) with human-mouse
      somatic hybrid cells containing human chromosome 17 and obtained several cDNA
      clones specific for this chromosome. A cDNA library from PHA-stimulated T cells
      was screened with unknown cDNA clones obtained by RDA as probes. Subsequently, 1
      complete gene and 1 partial cDNA clone were obtained. Our successful result
      implies that this subtractive amplification technique with hybrid cells will be a
      useful aid in positional cloning in large-spanning regions.

PMID- 9192861
TI  - Identification of translocational breakpoints within the intron region before the
      last coding exon (exon 12) of the EVI1 gene in two cases of CML-BC with
      inv(3)(q21q26).
AB  - We have previously shown that the EVI1 gene at chromosome 3q26 is
      transcriptionally activated by chromosomal rearrangements in acute myelogenous
      leukemias (AMLs) with inv(3)(q21q26) or t(3;3)(q21;q26). The breakpoints in
      t(3;3) cases were 15 to 330 kb upstream of the EVI1 gene, while those in inv(3)
      cases were 150 to 200 kb downstream and outside of the EVI1 coding region. The
      EVI1 gene is also activated in chronic myelogenous leukemia-blastic crisis (CML
      BC) with inv(3)(q21q26); however, the molecular mechanism of EVI1 activation in
      CML-BC is still unclear. In this paper, we have analyzed chromosomal
      rearrangements in two leukemia cell lines derived from CML-BC with inv(3)(q21q26)
      and have identified the breakpoints within the EVI1 coding area. The EVI1 gene
      spans over 100 kb with 12 exons (10 coding exons), and the chromosomal
      breakpoints are clustered in the intron region before the last coding exon (exon
      12). The nucleotide sequence of EVI1 cDNA clones from MOLM-1 cells was truncated
      at exon 11, and a novel sequence of 681 nucleotides was added at the 3' end of
      the EVI1 transcripts. The novel sequence was derived from a readthrough intron
      sequence 3' to the coding exon 11 adjacent to the breakpoint. The breakpoints at
      3q21 were within the breakpoint cluster area downstream of the ribophorin I gene,
      suggesting that the activation mechanism of the EVI1 gene in CMLs with inv(3) is
      the same as that in AMLs with inv(3). These results indicate that expression of a
      truncated EVI1 gene is an important factor in the progression of CML.

PMID- 9192862
TI  - Structure of the human type I iodothyronine 5'-deiodinase gene and localization
      to chromosome 1p32-p33.
AB  - The human type I iodothyronine 5'-deiodinase gene encodes a member of the family
      of selenocysteine-containing deiodinases. These enzymes catalyze the activation
      of the prohormone thyroxine to 3,3',5-triiodothyronine or the degradation of
      thyroxine and triiodothyronine to inactive metabolites. Here we report the
      isolation of two genomic type I 5'-deiodinase clones from a chromosome 1-specific
      gridded cosmid library, the localization of the gene to chromosome 1p32-p33 by
      fluorescence in situ hybridization, and the determination of the complete
      structure of the 17.5-kb gene.

PMID- 9192863
TI  - Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon
      amplification.

PMID- 9192864
TI  - The bg allele mutation is due to a LINE1 element retrotransposition.

PMID- 9192865
TI  - Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene
      eHand during murine heart development.
AB  - One of the first morphological manifestations of left/right (L/R) asymmetry in
      mammalian embryos is a pronounced rightward looping of the linear heart tube. The
      direction of looping is thought to be controlled by signals from an embryonic L/R
      axial system. We report here that morphological L/R asymmetry in the murine heart
      first became apparent at the linear tube stage as a leftward displacement of its
      caudal aspect. Beginning at the same stage, the basic helix-loop-helix (bHLH)
      factor gene eHand was expressed in a strikingly left-dominant pattern in
      myocardium, reflecting an intrinsic molecular asymmetry. In hearts of embryos
      lacking the homeobox gene Nkx2-5, which do not loop, left-sided eHand expression
      was abolished. However, expression was unaffected in Sc1-/- hearts that loop
      poorly because of hematopoietic insufficiency, and was right-sided in hearts of
      inv/inv embryos that display situs inversus. The data predict that eHand
      expression is enhanced in descendants of the left heart progenitor pool as one
      response to inductive signaling from the L/R axial system, and that eHand
      controls intrinsic morphogenetic pathways essential for looping. One aspect of
      the intrinsic response to L/R information falls under Nkx2-5 homeobox control.

PMID- 9192866
TI  - A family of LIM domain-associated cofactors confer transcriptional synergism
      between LIM and Otx homeodomain proteins.
AB  - The essential roles of LIM homeodomain proteins in cell fate determination during
      development have been demonstrated in organisms as divergent as Drosophila and
      higher mammals. We have isolated murine cDNAs encoding two highly homologous
      proteins that specifically interact with the LIM domains of P-Lim/Lhx3 and
      several other LIM homeodomain factors. Transcripts encoding these factors can be
      detected as early as mouse E8.5, with maximal expression observed in regions of
      the embryo in which the LIM homeodomain factors P-Lim/Lhx3, Isl-1, and LH-2 are
      selectively expressed. These proteins can potentiate transactivation by P-Lim/Lhx
      3 and are required for a synergistic activation of the glycoprotein hormone alpha
      subunit promoter by P-Lim/Lhx3 and a pituitary Otx class homeodomain
      transcription factor, with which they also specifically associate. Our results
      link LIM homeodomain proteins and members of the Otx class of transcription
      factors in gene activation events during embryogenesis via the actions of
      specific cofactors.

PMID- 9192867
TI  - Human TAF(II)135 potentiates transcriptional activation by the AF-2s of the
      retinoic acid, vitamin D3, and thyroid hormone receptors in mammalian cells.
AB  - We report for the first time the cloning of a complete cDNA encoding the human
      TFIID subunit hTAF(II)135 (hTAF(II)130). Full-length hTAF(II)135 comprises 1083
      amino acids and contains two conserved domains present also in dTAF(II)110 and
      hTAF(II)105. We show that expression of hTAF(II)135 in mammalian cells strongly
      and selectively potentiates transcriptional stimulation by the activation
      function-2 (AF-2) of the retinoic acid, thyroid hormone, and vitamin D3 receptors
      (RAR, TR, and VDR), but does not affect the AF-2s of the estrogen (ER) or
      retinoid X (RXR) receptors. The coactivator activity requires an hTAF(II)135
      region that is located between the conserved domains but is itself not conserved
      in dTAF(II)110 and hTAF(II)105. Expression of hTAF(II)135 also stimulates RAR AF
      2 activity when a promoter with a low-affinity TATA element (TGTA) is used,
      indicating that hTAF(II)135 overexpression compensates for the low-affinity of
      TBP for this promoter and may facilitate the recruitment of TFIID by the RAR AF
      2.

PMID- 9192868
TI  - Klumpfuss, a putative Drosophila zinc finger transcription factor, acts to
      differentiate between the identities of two secondary precursor cells within one
      neuroblast lineage.
AB  - The approximately 300 distinct neurons comprising each hemineuromere of the
      Drosophila embryonic central nervous system are derived from a segmentally
      reiterated array of approximately 30 progenitor cells, neuroblasts (NBs). Each NB
      has a unique identity and undergoes repeated cell divisions to produce several
      smaller secondary precursor cells, ganglion mother cells (GMCs); each GMC divides
      once to produce two neurons and/or glia, thereby generating a specific lineage of
      neurons/glia. Understanding the generation of neuronal diversity requires not
      only elucidation of the molecules and mechanisms that specify NB identity but
      also those that act to differentiate between the cell types produced within one
      NB lineage. Here we show that the Drosophila Zn finger protein Klumpfuss (Klu),
      which shows sequence similarities to the mammalian Wilm's tumor suppressor (WT
      1), acts to differentiate between the identities of the first two secondary
      precursor cells produced from one NB lineage. Klu is expressed in the NB4-2
      lineage only after two rounds of NB cell division, in the second born GMC (GMC4
      2b). In loss-of-function mutant embryos, the first born GMC (GMC4-2a) as well as
      its progeny neurons are duplicated; we show that this duplication of the GMC4-2a
      sublineage arises because GMC4-2b adopts the identity of GMC4-2a and divides to
      produce the GMC4-2a progeny. Moreover, when Klu is ectopically expressed in GMC4
      2a, it fails to acquire its normal identity and fails to produce correctly
      specified progeny. klu therefore acts to specify the identity of GMC4-2b and to
      make it distinct from GMC4-2a. Our findings further suggest that the
      determination of GMC cell fate occurs in two steps; the initial GMC identity is
      the consequence of inheritance from the maternal NB, however, the subsequent
      stabilization of this identity requires functions like klu in the GMC.

PMID- 9192869
TI  - The role of cyclin-dependent kinase 5 and a novel regulatory subunit in
      regulating muscle differentiation and patterning.
AB  - Cyclin-dependent kinase 5, coupled with its activator p35, is required for normal
      neuronal differentiation and patterning. We have isolated a novel member of the
      p35 family, Xp35.1, from Xenopus embryos which can activate cdk5. Xp35.1 is
      expressed in both proliferating and differentiated neural and mesodermal cells
      and is particularly high in developing somites where cdk5 is also expressed.
      Using dominant-negative cdk5 (cdk5 DN), we show that cdk5 kinase activity is
      required for normal somitic muscle development; expression of cdk5 DN results in
      disruption of somitic muscle patterning, accompanied by stunting of the embryos.
      Using explants of animal pole tissue from blastula embryos, which will
      differentiate into mesoderm in response to activin, we show that blocking cdk5
      kinase activity down-regulates the expression of the muscle marker muscle actin
      in response to activin, whereas the pan-mesodermal marker Xbra is unaffected.
      Expression of MyoD and MRF4 (master regulators of myogenesis) is suppressed in
      the presence of cdk5 DN, indicating that these myogenic genes may be a target for
      cdk5 regulation, whereas the related factor Myf5 is largely unaffected. In
      addition, overexpression of Xp35.1 disrupts muscle organization. Thus, we have
      demonstrated a novel role for cdk5 in regulating myogenesis in the early embryo.

PMID- 9192870
TI  - The an11 locus controlling flower pigmentation in petunia encodes a novel WD
      repeat protein conserved in yeast, plants, and animals.
AB  - In petunia flowers, the loci an1, an2, and an11 control the pigmentation of the
      flower by stimulating the transcription of anthocyanin biosynthetic genes. The
      an1 and an2 locus were recently cloned and encode a basic helix-loop-helix (bHLH)
      and MYB-domain transcriptional activator, respectively. Here, we report the
      isolation of the an11 locus by transposon tagging. RNA gel blot experiments show
      that an11 is expressed independently from an1 and an2 throughout plant
      development, as well as in tissues that do not express the anthocyanin pathway.
      It encodes a novel WD-repeat protein that is highly conserved even in species
      that do not produce anthocyanins such as yeast, nematodes, and mammals. The
      observation that the human an11 homolog partially complements the an11 petunia
      mutant in transient assays shows that sequence similarity reflects functional
      conservation. Overexpression of an2 in an11- petals restored the activity of a
      structural anthocyanin gene in transient assays, indicating that AN11 acts
      upstream of AN2. Cell fractionation experiments show that the bulk of the AN11
      protein is localized in the cytoplasm. Taken together, this indicates that AN11
      is a cytoplasmic component of a conserved signal transduction cascade that
      modulates AN2 function in petunia, thereby linking cellular signals with
      transcriptional activation.

PMID- 9192871
TI  - Mitogenic stimulation of resting T cells causes rapid phosphorylation of the
      transcription factor LSF and increased DNA-binding activity.
AB  - The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters
      modulated by cell growth signals. We demonstrate here that LSF-DNA-binding
      activity is strikingly regulated by induction of cell growth in human peripheral
      T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level
      of LSF-DNA-binding activity increased by a factor of five. The level of LSF
      protein in the nucleus remained constant throughout this interval. However, a
      rapid decrease in the electrophoretic mobility of LSF, attributable to
      phosphorylation, correlated with the increase in DNA-binding activity. pp44
      (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in
      vivo, specifically at amino acid position 291, as indicated by mutant analysis.
      As direct verification of the causal relationship between phosphorylation and DNA
      binding activity, treatment in vitro of LSF with phosphatase both increased the
      electrophoretic mobility of the protein and decreased LSF-DNA-binding activity.
      This modulation of LSF-DNA-binding activity as T cells progress from a resting to
      a replicating state reveals that LSF activity is regulated during cell growth and
      suggests that LSF regulates growth-responsive promoters.

PMID- 9192872
TI  - pRB and p107/p130 are required for the regulated expression of different sets of
      E2F responsive genes.
AB  - The activity of the E2F transcription factor is controlled by physical
      association with the retinoblastoma protein (pRB) and two related proteins, p107
      and p130. The pRB family members are thought to control different aspects of E2F
      activity, but it has been unclear what the respective functions of these proteins
      might be. To dissect the specific functions of pRB, p107, and p130 we have
      investigated how the expression of E2F-regulated genes is changed in cultures of
      primary cells lacking each of these family members. Whereas no changes were found
      in the expression of E2F-target genes in cells lacking either p107 or p130,
      deregulated expression of E2F targets was seen in cells lacking pRB and in cells
      lacking both p107 and p130. Surprisingly, the genes that were disregulated in
      these two settings were completely different. These findings show that pRB and
      p107/p130 indeed provide different functions in E2F regulation and identify
      target genes that are dependent on pRB family proteins for their normal
      expression.

PMID- 9192873
TI  - Cyclin E-CDK2 is a regulator of p27Kip1.
AB  - CDK inhibitors are thought to prevent cell proliferation by negatively regulating
      cyclin-CDK complexes. We propose that the opposite is also true, that cyclin-CDK
      complexes in mammmalian cells can promote cell cycle progression by directly down
      regulating CDK inhibitors. We show that expression of cyclin E-CDK2 in murine
      fibroblasts causes phosphorylation of the CDK inhibitor p27Kip1 on T187, and that
      cyclin E-CDK2 can directly phosphorylate p27 T187 in vitro. We further show that
      cyclin E-CDK2-dependent phosphorylation of p27 results in elimination of p27 from
      the cell, allowing cells to transit from G1 to S phase. Moreover, mutation of
      T187 in p27 to alanine creates a p27 protein that causes a G1 block resistant to
      cyclin E and whose level of expression is not modulated by cyclin E. A kinetic
      analysis of the interaction between p27 and cyclin E-CDK2 explains how p27 can be
      regulated by the same enzyme it targets for inhibition. We show that p27
      interacts with cyclin E-CDK2 in at least two distinct ways: one resulting in p27
      phosphorylation and release, the other in tight binding and cyclin E-CDK2
      inhibition. The binding of ATP to the CDK governs which state predominates. At
      low ATP (< 50 microM) p27 is primarily a CDK inhibitor, but at ATP concentrations
      approaching physiological levels (> 1 mM) p27 is more likely to be a substrate.
      Thus, we have identified p27 as a biologically relevant cyclin E-CDK2 substrate,
      demonstrated the physiological consequences of p27 phosphorylation, and developed
      a kinetic model to explain how p27 can be both an inhibitor and a substrate of
      cyclin E-CDK2.

PMID- 9192874
TI  - Cyclin E-induced S phase without activation of the pRb/E2F pathway.
AB  - In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and,
      possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase
      transition, by phosphorylating the retinoblastoma protein (pRb), thereby
      releasing E2F transcription factors that control S-phase genes. Here we performed
      microinjection and transfection experiments using rat R12 fibroblasts, their
      derivatives conditionally overexpressing cyclins D1 or E, and human U-2-OS cells,
      to explore the action of G1 cyclins and the relationship of E2F and cyclin E in S
      phase induction. We demonstrate that ectopic expression of cyclin E, but not
      cyclin D1, can override G1 arrest imposed by either the p16INK4a Cdk inhibitor
      specific for Cdk4 and Cdk6 or a novel phosphorylation-deficient mutant pRb.
      Several complementary approaches to assess E2F activation, including quantitative
      reporter assays in live cells, showed that the cyclin E-induced S phase and
      completion of the cell division cycle can occur in the absence of E2F-mediated
      transactivation. Together with the ability of cyclin E to overcome a G1 block
      induced by expression of dominant-negative mutant DP-1, a heterodimeric partner
      of E2Fs, these results provide evidence for a cyclin E-controlled S phase
      promoting event in somatic cells downstream of or parallel to phosphorylation of
      pRb and independent of E2F activation. They furthermore indicate that a lack of
      E2F-mediated transactivation can be compensated by hyperactivation of this cyclin
      E-controlled event.

PMID- 9192875
TI  - 'No change' while NIH revises peer review.

PMID- 9192877
TI  - US opens reagent repository to boost malaria vaccine research.

PMID- 9192876
TI  - White House bill would ban human cloning.

PMID- 9192878
TI  - Funding for malaria genome sequencing.

PMID- 9192879
TI  - Demise of the monograph.

PMID- 9192880
TI  - Events at Jena institute.

PMID- 9192881
TI  - Biology, not microbiology.

PMID- 9192882
TI  - Human genetics. A father's imprint on his daughter's thinking.

PMID- 9192883
TI  - Transcriptional activation. Something new to hang your HAT on.

PMID- 9192884
TI  - Reductionism. The ends of understanding.

PMID- 9192885
TI  - Microbial genetics. The tinkerer's evolving tool-box.

PMID- 9192886
TI  - Origins of life. The first two billion years.

PMID- 9192887
TI  - John C. Eccles (1903-97)

PMID- 9192888
TI  - Long-term potentiation in awake mutant mice.

PMID- 9192889
TI  - Rhodopsin evolution in the dark.

PMID- 9192890
TI  - Chirality errors in nucleic acid structures.

PMID- 9192891
TI  - Signalling through the lipid products of phosphoinositide-3-OH kinase.
AB  - When a stimulatory agonist molecule binds at the exterior of the cell membrane, a
      second messenger transduces the signal to the interior of the cell. Second
      messengers can be derived from phospholipids in the membrane by the action of the
      enzymes phospholipase C or phosphoinositide-3-OH kinase (PI(3)K). PI(3)K is a key
      player in many cellular responses, including the movement of organelle membranes,
      shape alteration through rearrangement of cytoskeletal actin, transformation and
      chemotaxis. But how PI(3)K mediates these responses is only now becoming clear.

PMID- 9192892
TI  - The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor
      function.
AB  - The functionally conserved proteins CBP and p300 act in conjunction with other
      factors to activate transcription of DNA. A new factor, p/CIP, has been
      discovered that is present in the cell as a complex with CBP and is required for
      transcriptional activity of nuclear receptors and other CBP/p300-dependent
      transcription factors. The highly related nuclear-receptor co-activator protein
      NCoA-1 is also specifically required for ligand-dependent activation of genes by
      nuclear receptors. p/CIP, NCoA-1 and CBP all contain related leucine-rich charged
      helical interaction motifs that are required for receptor-specific mechanisms of
      gene activation, and allow the selective inhibition of distinct signal
      transduction pathways.

PMID- 9192893
TI  - Role of mutator alleles in adaptive evolution.
AB  - Because most newly arising mutations are neutral or deleterious, it has been
      argued that the mutation rate has evolved to be as low as possible, limited only
      by the cost of error-avoidance and error-correction mechanisms. But up to one per
      cent of natural bacterial isolates are 'mutator' clones that have high mutation
      rates. We consider here whether high mutation rates might play an important role
      in adaptive evolution. Models of large, asexual, clonal populations adapting to a
      new environment show that strong mutator genes (such as those that increase
      mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene
      remains at a very low frequency (for example, 10[-5]). Less potent mutators (10
      to 100-fold increase) can become fixed in a fraction of finite populations. The
      parameters of the model have been set to values typical for Escherichia coli
      cultures, which behave in a manner similar to the model in long-term adaptation
      experiments.

PMID- 9192894
TI  - Evolution of high mutation rates in experimental populations of E. coli.
AB  - Most mutations are likely to be deleterious, and so the spontaneous mutation rate
      is generally held at a very low value. Nonetheless, evolutionary theory predicts
      that high mutation rates can evolve under certain circumstances. Empirical
      observations have previously been limited to short-term studies of the fates of
      mutator strains deliberately introduced into laboratory populations of
      Escherichia coli, and to the effects of intense selective events on mutator
      frequencies in E. coli. Here we report the rise of spontaneously originated
      mutators in populations of E. coli undergoing long-term adaptation to a new
      environment. Our results corroborate computer simulations of mutator evolution in
      adapting clonal populations, and may help to explain observations that associate
      high mutation rates with emerging pathogens and with certain cancers.

PMID- 9192895
TI  - Evidence from Turner's syndrome of an imprinted X-linked locus affecting
      cognitive function.
AB  - Turner's syndrome is a sporadic disorder of human females in which all or part of
      one X chromosome is deleted. Intelligence is usually normal but social adjustment
      problems are common. Here we report a study of 80 females with Turner's syndrome
      and a single X chromosome, in 55 of which the X was maternally derived (45,X[m])
      and in 25 it was of paternal origin (45,X[p]). Members of the 45,X[p] group were
      significantly better adjusted, with superior verbal and higher-order executive
      function skills, which mediate social interactions. Our observations suggest that
      there is a genetic locus for social cognition, which is imprinted and is not
      expressed from the maternally derived X chromosome. Neuropsychological and
      molecular investigations of eight females with partial deletions of the short arm
      of the X chromosome indicate that the putative imprinted locus escapes X
      inactivation, and probably lies on Xq or close to the centromere on Xp. If
      expressed only from the X chromosome of paternal origin, the existence of this
      locus could explain why 46,XY males (whose single X chromosome is maternal) are
      more vulnerable to developmental disorders of language and social cognition, such
      as autism, than are 46,XX females.

PMID- 9192896
TI  - Molecular evidence for an ancient duplication of the entire yeast genome.
AB  - Gene duplication is an important source of evolutionary novelty. Most
      duplications are of just a single gene, but Ohno proposed that whole-genome
      duplication (polyploidy) is an important evolutionary mechanism. Many duplicate
      genes have been found in Saccharomyces cerevisiae, and these often seem to be
      phenotypically redundant. Here we show that the arrangement of duplicated genes
      in the S. cerevisiae genome is consistent with Ohno's hypothesis. We propose a
      model in which this species is a degenerate tetraploid resulting from a whole
      genome duplication that occurred after the divergence of Saccharomyces from
      Kluyveromyces. Only a small fraction of the genes were subsequently retained in
      duplicate (most were deleted), and gene order was rearranged by many reciprocal
      translocations between chromosomes. Protein pairs derived from this duplication
      event make up 13% of all yeast proteins, and include pairs of transcription
      factors, protein kinases, myosins, cyclins and pheromones. Tetraploidy may have
      facilitated the evolution of anaerobic fermentation in Saccharomyces.

PMID- 9192897
TI  - A dendritic-cell-derived C-C chemokine that preferentially attracts naive T
      cells.
AB  - Dendritic cells form a system of highly efficient antigen-presenting cells. After
      capturing antigen in the periphery, they migrate to lymphoid organs where they
      present the antigen to T cells. Their seemingly unique ability to interact with
      and sensitize naive T cells gives dendritic cells a central role in the
      initiation of immune responses and allows them to be used in therapeutic
      strategies against cancer, viral infection and other diseases. How they interact
      preferentially with naive rather than activated T lymphocytes is still poorly
      understood. Chemokines direct the transport of white blood cells in immune
      surveillance. Here we report the identification and characterization of a C-C
      chemokine (DC-CK1) that is specifically expressed by human dendritic cells at
      high levels. Tissue distribution analysis demonstrates that dendritic cells
      present in germinal centres and T-cell areas of secondary lymphoid organs express
      this chemokine. We show that DC-CK1, in contrast to RANTES, MIP-1alpha and
      interleukin-8, preferentially attracts naive T cells (CD45RA+). The specific
      expression of DC-CK1 by dendritic cells at the site of initiation of an immune
      response, combined with its chemotactic activity for naive T cells, suggests that
      DC-CK1 has an important rule in the induction of immune responses.

PMID- 9192898
TI  - A GPI-linked protein that interacts with Ret to form a candidate neurturin
      receptor.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two
      structurally related, potent survival factors for sympathetic, sensory and
      central nervous system neurons. GDNF mediates its actions through a
      multicomponent receptor system composed of a ligand-binding glycosyl
      phosphatidylinositol (GPI)-linked protein (designated GDNFR-alpha) and the
      transmembrane protein tyrosine kinase Ret. In contrast, the mechanism by which
      the NTN signal is transmitted is not well understood. Here we describe the
      identification and tissue distribution of a GPI-linked protein (designated NTNR
      alpha) that is structurally related to GDNFR-alpha. We further demonstrate that
      NTNR-alpha binds NTN (K[d] approximately 10 pM) but not GDNF with high affinity;
      that GDNFR-alpha binds to GDNF but not NTN with high affinity; and that cellular
      responses to NTN require the presence of NTNR-alpha. Finally, we show that NTN,
      in the presence of NTNR-alpha, induces tyrosine-phosphorylation of Ret, and that
      NTN, NTNR-alpha and Ret form a physical complex on the cell surface. These
      findings identify Ret and NTNR-alpha as signalling and ligand-binding components,
      respectively, of a receptor for NTN and define a novel family of receptors for
      neurotrophic and differentiation factors composed of a shared transmembrane
      protein tyrosine kinase and a ligand-specific GPI-linked protein.

PMID- 9192899
TI  - Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor
      tyrosine kinase.
AB  - Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived
      neurotrophic factor (GDNF). Both factors promote the survival of a variety of
      neurons, and GDNF is required for the development of the enteric nervous system
      and kidney. GDNF signals through a receptor complex consisting of the receptor
      tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor
      termed GDNFR-alpha. Here we report the cloning of a new GPI-linked receptor
      termed NTNR-alpha that is homologous with GDNFR-alpha and is widely expressed in
      the nervous system and other tissues. By using microinjection to introduce
      expression plasmids into neurons, we show that coexpression of NTNR-alpha with
      Ret confers a survival response to neurturin but not GDNF, and that coexpression
      of GDNFR-alpha with Ret confers a survival response to GDNF but not neurturin.
      Our findings indicate that GDNF and neurturin promote neuronal survival by
      signalling through similar multicomponent receptors that consist of a common
      receptor tyrosine kinase and a member of a GPI-linked family of receptors that
      determines ligand specificity.

PMID- 9192900
TI  - Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1.
AB  - The actin cytoskeleton is regulated by GTP-hydrolysing proteins, the Rho GTPases,
      which act as molecular switches in diverse signal-transduction processes. Various
      bacterial toxins can inactivate Rho GTPases by ADP-ribosylation or glucosylation.
      Previous research has identified Rho proteins as putative targets for Escherichia
      coli cytotoxic necrotizing factors 1 and 2 (CNF1 and 2). These toxins induce
      actin assembly and multinucleation in culture cells. Here we show that treatment
      of RhoA with CNF1 inhibits the intrinsic GTPase activity of RhoA and completely
      blocks GTPase activity stimulated by the Rho-GTPase-activating protein (rhoGAP).
      Analysis by mass spectrometry and amino-acid sequencing of proteolytic peptides
      derived from CNF1-treated RhoA indicate that CNF1 induces deamidation of a
      glutamine residue at position 63 (Gln 63) to give constitutively active Rho
      protein.

PMID- 9192901
TI  - Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine.
AB  - Pathogenic Escherichia coli are responsible for a variety of diseases, including
      diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia
      and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the
      virulence factors produced by uropathogenic (CNF1) or enteropathogenic (CNF2) E.
      coli strains that cause diseases in humans and animals, respectively. CNFs induce
      an increase in the content of actin stress fibres and focal contacts in cultured
      cells. Effects of CNFs on the actin cytoskeleton correlated with a decrease in
      the electrophoretic mobility of the GTP-binding protein Rho and indirect evidence
      indicates that CNF1 might constitutively activate Rho. Here we show that CNF1
      catalyses the deamidation of a glutamine residue at position 63 of Rho, turning
      it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that
      stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of
      glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the
      reorganization of actin stress fibres. To our knowledge, CNF1 is the first
      example of a bacterial toxin acting by deamidation of a specific target protein.

PMID- 9192903
TI  - Enalapril and pressure-diuresis in hypertensive rats transgenic for mouse renin
      gene.
AB  - The recent development of a transgenic rat strain bearing the mouse ren-2 renin
      gene [TGR(mRen2)27] has provided a new monogenetic model of hypertension. Other
      hypertensive rat strains are characterized by a blunted pressure-diuresis
      natriuresis response such that higher renal perfusion pressures are required to
      excrete normal amounts of water and sodium. Dysfunction of the renin-angiotensin
      and nitric oxide systems may cause in this abnormality. This study examined the
      effect of enalapril on the pressure-natriuresis response and urinary nitric oxide
      metabolite excretion in 6-month-old TGR(mRen2)27 rats. The slope of the line
      relating renal perfusion pressure and urine flow rate in TGR (0.08+/-0.01 microl
      x min(-1) x g kidney weight(-1) mm Hg[-1]) was significantly lower than that in
      control rats (0.15+/-0.01 microl x min(-1) x g kidney weight(-1) mm Hg[-1]).
      Pressure-natriuresis responses were also shifted to higher pressure levels in
      TGR. Treatment with enalapril for 3 months lowered the mean arterial pressure
      from 94+/-2 to 84+/-4 mm Hg in control rats and from 146+/-3 to 89+/-3 mm Hg in
      TGR. The slopes of lines relating renal perfusion pressure and urine flow rate as
      well as sodium excretion were significantly increased by enalapril in control and
      transgenic animals. Urinary nitric oxide metabolite excretion rose similarly with
      increasing renal perfusion pressure in both control and TGR rats and was not
      affected by enalapril. These results confirm that older TGR rats have a blunted
      pressure-diuresis-natriuresis response that can be corrected by inhibition of the
      renin-angiotensin system and suggest that their production of nitric oxide is
      normal.

PMID- 9192904
TI  - Influence of the renal endothelin system on the autoregulation of renal blood
      flow in spontaneously hypertensive rats.
AB  - The renal endothelin (ET) system has been claimed to play an important role in
      the regulation of renal blood flow (RBF) and sodium excretion in primary
      hypertension. The aim of the present study was to investigate the contribution of
      the endogenous ET system in the autoregulation of total RBF, cortical blood flow
      (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in
      spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor
      antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow
      probes and CBF by laser flow probes. During the experiments, the rats received an
      intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion
      pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled
      electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect
      on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by
      30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of
      RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure
      dependent PRA and pressure natriuresis were observed. Our findings demonstrate a
      significant impairment in total RBF autoregulatory ability during renal ET
      receptor blockade which is not confined to the cortical vessels. These data
      suggest that the renal ET system plays an important role in the dynamic
      regulation of renal blood flow in SHR.

PMID- 9192905
TI  - Autoregulation of total and zonal glomerular filtration rate in spontaneously
      hypertensive rats with mesangiolysis.
AB  - In this study we tested the hypothesis that mesangial cells participate in
      autoregulation of the glomerular filtration rate (GFR) in normotensive and
      hypertensive rats. Mesangial cell lesions were induced by intravenous
      administration of antithymocyte (anti-Thy 1.1) antibodies in spontaneously
      hypertensive rats (SHR) and in Wistar-Kyoto rats (WKY). Normal murine serum was
      injected in control rats. Hemodynamic measurements were performed 24 h after the
      infusion of the anti-Thy 1.1 antibodies. Renal blood flow (RBF) was measured by a
      transit time flowmeter (Transonic) and the GFR was measured as the uptake of 125
      iodine-labeled aprotinin ([125]I-Ap) by proximal tubular cells at the control
      renal arterial pressure and (131)I-Ap at a pressure reduction close to the lower
      pressure limit of RBF autoregulation. RBF was unaltered and the autoregulatory
      capability was maintained in SHR and WKY after mesangial cell lesions.
      Mesangiolysis significantly reduced the total GFR in normotensive, but not in
      hypertensive animals. The fractional compensation of the GFR was attenuated in
      the outer cortical layer (p<0.05) in normotensive WKY. In SHRs the fractional
      compensation of the GFR was impaired in all cortical layers after mesangiolysis,
      slightly more in the outer than in the inner cortex. We conclude that mesangial
      cells may contribute to the autoregulation of GFR in hypertensive rats, but to a
      lesser extent in normotensive rats.

PMID- 9192902
TI  - A signature motif in transcriptional co-activators mediates binding to nuclear
      receptors.
AB  - The binding of lipophilic hormones, retinoids and vitamins to members of the
      nuclear-receptor superfamily modifies the DNA-binding and transcriptional
      properties of these receptors, resulting in the activation or repression of
      target genes. Ligand binding induces conformational changes in nuclear receptors
      and promotes their association with a diverse group of nuclear proteins,
      including SRC-1/p160, TIF-2/GRIP-1 and CBP/p300 which function as co-activators
      of transcription, and RIP-140, TIF-1 and TRIP-1/SUG-1 whose functions are
      unclear. Here we report that a short sequence motif LXXLL (where L is leucine and
      X is any amino acid) present in RIP-140, SRC-1 and CBP is necessary and
      sufficient to mediate the binding of these proteins to liganded nuclear
      receptors. We show that the ability of SRC-1 to bind the oestrogen receptor and
      enhance its transcriptional activity is dependent upon the integrity of the LXXLL
      motifs and on key hydrophobic residues in a conserved helix (helix 12) of the
      oestrogen receptor that are required for its ligand-induced activation function.
      We propose that the LXXLL motif is a signature sequence that facilitates the
      interaction of different proteins with nuclear receptors, and is thus a defining
      feature of a new family of nuclear proteins.

PMID- 9192906
TI  - Role of atrial natriuretic factor, hemodynamic changes and renal nerves in the
      renal effects of intraperitoneal morphine in conscious rats.
AB  - The aim of the present study was to investigate the role of renal nerves and
      atrial natriuretic factor (ANF) in the mechanisms responsible for the diuresis
      and antinatriuresis induced by morphine in rats in a normal state of hydration.
      Male Wistar rats weighing 350-400 g were divided into two groups: one group was
      subjected to bilateral renal denervation, whereas the other consisted of sham
      operated controls. The animals were placed in individual metabolic cages, and
      morphine (1.25, 2.5, 5.0 or 10.0 mg/kg body weight) or vehicle (0.5 ml isotonic
      saline) was injected intraperitoneally. Urine was collected hourly for 1 h before
      and 3 h after morphine injection. The lower doses of morphine (1.25 and 2.5 mg/kg
      body weight) induced a transient increase in urine output (from 1.17+/-0.12 to
      2.49+/-0.34 and from 0.78+/-0.08 to 1.71+/-0.18 microl/min, respectively). The
      diuretic response to these doses was similar in bilaterally denervated rats.
      Higher doses (5.0 and 10.0 mg/kg body weight) induced a marked but transient
      reduction in the urinary flow rate during the first hour (from 0.90+/-0.11 to
      0.48+/-0.05 and from 1.37+/-0.17 to 0.45+/-0.08 microl/min, respectively),
      followed by a delayed diuretic effect. The antidiuretic action of morphine was
      not observed in bilaterally denervated rats. In control rats, morphine induced a
      dose-dependent decrease in sodium excretion 1 h after administration, an effect
      that was blunted in the denervated group. The lower morphine doses (1.25 and 2.5
      mg/kg body weight) elicited a transient increase in the glomerular filtration
      rate (GFR) in both control (from 1.23+/-0.12 to 1.67+/-0.17 and from 1.28+/-0.14
      to 2.41+/-0.18 ml/min) and bilaterally denervated rats (from 1.29+/-0.14 to
      1.66+/-0.17 and from 1.18+/-0.22 to 1.72+/-0.19 ml/min), whereas the higher doses
      (5.0 and 10.0 mg/kg body weight) produced a marked, transient GFR decrease in the
      controls (from 1.25+/-0.11 to 0.43+/-0.05 and from 1.13+/-0.17 to 0.47+/-0.08
      ml/min) and bilaterally denervated animals (from 1.48+/-0.16 to 0.74+/-0.09 and
      from 1.22+/-0.15 to 0.73+/-0.06 ml/min), although the reduction was less
      pronounced with renal denervation. Morphine induced a transient, dose-dependent
      reduction in blood pressure (from 114+/-1 to 71+/-6 mm Hg at 10.0 mg/kg body
      weight) and a dose-dependent elevation of plasma ANF. No differences in plasma
      ANF were observed between control and denervated animals under basal conditions
      (60+/-7 vs. 42+/-6 pg/ml) or after injection of 2.5 or 5.0 mg/kg of morphine
      (155+/-11 vs. 167+/-9 and 360+/-9 vs. 401+/-9 pg/ml, respectively). Our data
      suggest that the renal responses to intraperitoneal morphine administration
      derive from the integration of several different actions: (1) increased ANF
      release; (2) decreased arterial pressure; (3) subsequent activation of renal
      sympathetic activity, and (4) the direct effect of morphine on tubular function.

PMID- 9192907
TI  - Direct effects of platelet-activating factor on glomerular capillary
      permeability.
AB  - Platelet-activating factor (PAF) is an important mediator of injury in acute
      renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces
      glomerular filtration rate and renal plasma flow and increases glomerular
      permselectivity via its renal hemodynamic and/or immunologic effects. Direct
      effects of PAF on glomerular capillary permeability are not known. We studied the
      direct effects of PAF on mesangial contraction (a measure of filtration area),
      glomerular capillary hydraulic conductivity (L[p]) and capillary albumin
      permeability (P[albumin]). Glomeruli were isolated from Sprague-Dawley rats and
      incubated with or without various concentrations of PAF (10[-9], 10[-7] and 10[
      5] M) for up to 5 h at 37 degrees C. Mesangial contraction (percent change in
      glomerular volume) was assessed from the gradual decrease in volume of glomeruli
      during 20 min of incubation with PAF. L(p) was calculated from the rate of change
      in glomerular volume during the 0.1 s of capillary expansion in response to a
      transcapillary oncotic gradient. P(albumin) was calculated from a change in
      relative volume of glomeruli in response to an oncotic gradient. Mesangial
      contraction was maximal after 20 min of incubation and was concentration
      dependent (5.2+/-0.9, 7.9+/-1.0 and 10.0+/-1.0%, respectively, with PAF 10(-9),
      10(-7) and 10(-5) M). Incubation of glomeruli with PAF 10(-7) M for 60 min at 37
      degrees C caused a significant decrease in L(p) (2.25+/-0.30 vs. control 3.12+/
      0.28 microl x min(-1) x mm Hg(-1) x cm(-1), n = 5). P(albumin) of glomeruli
      incubated with PAF was unchanged up to 2 h but increased significantly with the
      highest concentration of PAF (10(-5) M) after 3 h of incubation (0.60+/-0.18,
      n=15, vs. control 0.00+/-0.08, n = 20), whereas lower concentrations of PAF (10[
      7] or 10[-9] M) required at least 5 h of incubation with glomeruli to cause a
      significant increase in P(albumin) (0.45+/-0.09 and 0.48+/-0.07, respectively,
      n=15, vs. control 0.00+/-0.08, n=15). We conclude that PAF has multiple direct
      effects on glomerular functions, which are time dependent and may contribute to
      the altered capillary permeability in vivo.

PMID- 9192909
TI  - Reduction of chronic ciclosporin nephrotoxicity by thromboxane synthase
      inhibition with OKY-046.
AB  - Ciclosporin A (CsA) is a potent immunosuppressive agent which is extremely
      effective in controlling allograft rejection and in the treatment of autoimmune
      disease and nephrotic syndrome. Unfortunately, its use is limited by chronic,
      irreversible nephrotoxicity. Administration of CsA induces renal
      vasoconstriction, causing a reduction in renal blood flow. An alteration of the
      prostaglandin-thromboxane cascade may be involved in the vasoconstriction. We
      studied the role of thromboxane A2 in CsA nephrotoxicity and the ability of a
      thromboxane synthase inhibitor, OKY-046, to reduce the CsA nephrotoxicity. Daily
      administration of CsA 25 mg/kg for 28 days to Sprague-Dawley rats resulted in
      increased excretion of urinary thomboxane B2 (47.9+/-11.5 vs. 27.2+/-9.7 ng/24 h;
      p<0.05) and decreased creatinine clearance (0.25+/-0.07 vs. 0.43+/-0.17ml/min/100
      g; p<0.01) as compared with administration of vehicle only. Histologically, large
      numbers of lysosomes in the tubular epithelium were characteristic.
      Coadministration of OKY-046 prevented both the rise in urinary thromboxane B2
      excretion (40.0+/-11.8 ng/24 h) and the reduction in the creatinine clearance
      (0.44+/-0.11 ml/min/100 g). The severity of the histological changes was
      significantly diminished. Selective inhibition of thromboxane production with OKY
      046 may be valuable in the attenuation of CsA nephrotoxicity.

PMID- 9192908
TI  - Effect of adrenalectomy on distal nephron lithium reabsorption induced by
      potassium depletion.
AB  - In potassium-depleted rats lithium is reabsorbed by an amiloride-sensitive
      transport mechanism in the distal nephron segments, and the urinary fractional
      excretion of lithium (FE[Li]) is reduced by almost 50% compared to that of
      potassium-replete rats. We have used renal clearance techniques to study the
      effects of adrenalectomy (Adx) or sham operation on amiloride-sensitive lithium
      reabsorption in conscious potassium-deprived (K5) and control (K200) rats. In the
      sham-operated rats, administration of a low potassium diet led to a significant
      reduction in FE(Li) from 27.0 to 16.6% (p < 0.01), whereas in the Adx rats the
      reduction in FE(Li) was smaller (from 27.0 to 22.6) and not statistically
      significant. Urinary sodium excretion was similar (1,100 nmol/min/100 g body
      weight) in all groups. During subsequent amiloride infusion in order to block the
      distal nephron reabsorption of lithium, urinary sodium excretion increased nearly
      twofold in the sham-operated groups whereas no change was evident in the Adx
      rats. Similarly, amiloride led to an increase in FE(Li) in the sham-K5 group but
      failed to increase FE(Li) in the Adx-K5 group. The results suggest that amiloride
      sensitive lithium transport seen during potassium depletion is influenced by the
      presence of the adrenal glands, most likely due to their production of
      aldosterone.

PMID- 9192910
TI  - The ovaries attenuate the aggravating effect of testosterone on glomerular injury
      in Adriamycin-induced nephropathy of female rats.
AB  - To clarify whether the ovaries have a potential to attenuate the aggravating
      effect of testosterone (T) on glomerular injury, we investigated the effect of T
      in female rats with or without ovaries, using Adriamycin (ADR)-induced
      nephropathy in female Sprague-Dawley rats. Group 1 consisted of female control
      rats, group 2 received T, groups 3 and 4 were subjected to ovariectomy (OVX) at 5
      weeks of age, and group 4 received further T treatment. Group 5 consisted of male
      control rats. T was injected subcutaneously every 4 weeks from 5 weeks of age
      through the end of the experiment. ADR 2 mg/kg was administered intravenously to
      all rats twice, at 8 weeks of age and 20 days later. Body weight, blood pressure,
      urinary protein and serum constituents were investigated every 4 weeks from 4
      through 24 weeks after the second ADR injection. Each group was studied
      morphologically 24 weeks after the second ADR injection. Treatment with T or with
      OVX and T significantly increased the urinary protein excretion. OVX had no
      significant effect on the urinary protein excretion. Treatment with either T or
      OVX did not induce any significant effects on the renal function with regard to
      blood urea nitrogen (BUN), serum creatinine (Cr) and Cr clearance (Ccr) levels,
      but a combined treatment with OVX and T significantly lowered the serum albumin
      levels, increased the levels of BUN and Cr and lowered the Ccr values. The
      glomerulosclerosis index was significantly and markedly higher in control male
      rats than in control females. Treatment with T resulted in a slight but
      significant increase in glomerular injury to levels similar to those seen in
      ovariectomized rats. Combined treatment with OVX and T significantly aggravated
      glomerular injury in a somewhat accelerated manner, associated with a significant
      increase in glomerular tuft volume. Our results suggested that the ovaries could
      not completely suppress glomerular injury worsened by T administered at serum
      levels similar to those of male rats, but they had a potential to attenuate
      glomerular injury induced by T, and the protective effect of the ovaries on
      glomerular injury may be related to their attenuating effect on glomerular
      growth.

PMID- 9192911
TI  - Testosterone does not eliminate the attenuating effect of estrogen on progressive
      glomerular injury in estrogen-treated hypercholesterolemic male Imai rats.
AB  - Hypercholesterolemic Imai rats spontaneously develop proteinuria and
      glomerulosclerosis, especially males. Estrogen attenuates the progressive
      glomerular injury in these male rats. To clarify whether this attenuating effect
      of estrogen depends on a reduction of testosterone and/or a reduction of the sex
      related factors, we investigated whether testosterone administration eliminates
      the attenuating effect of estrogen on the development of glomerular injury in
      estrogen-treated male Imai rats. Estrogen significantly reduced sex-related low
      molecular weight protein excretion to undetectable levels; and treatment with
      estrogen and testosterone failed to increase these levels. Unexpectedly,
      treatment with estrogen and testosterone attenuated glomerular injury more than
      treatment with estrogen only. Estrogen significantly increased both levels of
      estrogen and growth hormone (GH), whereas it suppressed testosterone levels.
      Testosterone administration resulted in an increase in serum testosterone levels
      of about fivefold above the control levels, but reduced the elevated serum GH to
      the levels of the controls. These results suggest that estrogen appears to play a
      protective role by itself or in association with sex-related factors, independent
      of the levels of serum testosterone, and that testosterone does not exert its
      effect on augmenting glomerular injury and rather may act to attenuate glomerular
      injury associated with a reduction of GH levels.

PMID- 9192912
TI  - The effect of ammonium chloride on hepatic and renal metabolism in the rat.
AB  - The metabolic effects of an ammonium salt on the liver and kidney were
      investigated. Rats were allowed free access to a 0.28 M ammonium chloride (NH4Cl)
      solution for 7- and 8-day periods. Serum urea concentration was significantly
      increased after 8 days of NH4Cl ingestion. However the following hepatic urea
      cycle enzymes remained unchanged: CPS, OTC, ASS and ASL. The pattern of urinary
      urea excretion was variable. When the data for the 7-day period were pooled,
      there was no significant difference between the control and acidotic groups.
      However, when they were examined on a daily basis, acidosis significantly
      decreased urea excretion on day 2. Urea excretion then began to increase, reached
      the control value on day 4 and was significantly greater than the control value
      on day 7. Urinary ammonium excretion of the acidotic group was significantly
      increased on day 2 and continued to rise throughout the 7-day period. Renal
      phosphate-dependent glutaminase of the acidotic group was significantly increased
      on the eighth day. These data indicate that NH4Cl ingestion alters the pattern of
      urea excretion in a manner not previously demonstrated.

PMID- 9192913
TI  - Coexistent gout and Mycobacterium avium-intracellulare arthritis in a renal
      transplant recipient.
AB  - Infectious arthritis in renal transplant patients may be a commonly diagnosed
      condition with traditional bacterial organisms isolated. However, since
      nontuberculous mycobacteria are ubiquitous in the environment, immunocompromised
      individuals may suffer from infections with these organisms. Concomitant gout and
      Mycobacterium avium intracellulare septic arthritis is described for the first
      time in this clinical setting. Appropriate cultures should be performed even in
      the setting of crystal arthritis in posttransplant patients when clinically
      indicated.

PMID- 9192914
TI  - Mechanism of hypouricemia in a child with the normotensive form of Gordon's
      syndrome.
AB  - The mechanism of renal tubular urate transport disorder was studied by the
      pyrazinamide and probenecid tests in a 12-year-old hypouricemic boy suffering
      from the normotensive form of Gordon's syndrome, with increased distal tubular
      reabsorption of NaCl (confirmed by the hypotonic saline diuresis test). The aim
      of the study was to determine the impact of oral hydration during the tests on
      the phases of renal tubular urate transport: before (I), and during long-term
      hydrochlorothiazide therapy (0.5 mg/kg BW/day) (II). In both periods (I,II),
      presecretory reabsorption of urate was within normal limits. Hypouricemia in our
      patient was caused by decreased postsecretory reabsorption, with or without
      simultaneous increase of tubular urate secretion. The degree of overhydration
      determines which of these mechanisms is responsible for increased renal urate
      clearance.

PMID- 9192915
TI  - Chemokines are important cytokines in the pathogenesis of interstitial lung
      disease.

PMID- 9192916
TI  - Environmental control: an idea whose time has come.

PMID- 9192917
TI  - Measurement of lung volumes in humans: review and recommendations from an ATS/ERS
      workshop.

PMID- 9192918
TI  - The source and role of RANTES in interstitial lung disease.
AB  - The chemokine "regulated on activation, normal T-cell expressed and secreted"
      (RANTES) is a potent eosinophil and lymphocyte attractant with particular
      preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the
      lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this
      study was to determine whether RANTES mediates the inflammatory cell influx in
      these diffuse lung diseases. Cell types and number of bronchoalveolar cells
      expressing RANTES protein were investigated by immunocytochemistry using lavage
      cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES
      messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription
      polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets
      in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were
      identified by in situ hybridization. RANTES protein expression in lower
      respiratory tract (LRT) cells was identified in all study groups. The percentage
      of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was
      localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in
      sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing
      alveolitis. The same cell types which expressed RANTES protein expressed RANTES
      mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher
      levels of RANTES mRNA than the other groups. RANTES protein was higher in
      individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression
      was significantly correlated with lavage CD45RO+ lymphocyte numbers. These
      results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung
      disease, particularly sarcoidosis. Moreover, they suggest that the cellular
      source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages
      and eosinophils in fibrosing alveolitis.

PMID- 9192920
TI  - Asthma in Greenwich, UK: impact of the disease and current management practices.
AB  - A great deal of the care of patients with asthma takes place in general
      practices. The aim of the present study was to describe the impact of asthma in
      the community and to identify current asthma self-management practices. A two
      part questionnaire survey was conducted in a random sample (23%; n=24,398) of
      persons aged 16-50 yrs, registered with one of the 41 general practices in
      Greenwich, London, UK. The two parts were: a screening questionnaire identifying
      persons with current asthma (defined as waking with shortness of breath in the
      last 12 months, attack of asthma in the last 12 months, or currently taking
      treatment for asthma); and an asthma questionnaire (completed by those with
      asthma) assessing quality of life, frequency of asthma symptoms, possession and
      use of self-management tools, and action in the event of an exacerbation of
      asthma. The crude response rate was 51%, but this may be an underestimate due to
      errors in the sampling frame. The prevalences of wheeze and asthma in the past 12
      months were 26% and 14%, respectively. Among asthma patients: 43% reported
      symptoms occurring three or more times per week, and 20% were woken by asthma
      symptoms on three or more nights per week; most had asthma with a mild impact on
      quality of life; 26% used inhaled steroids on most days in the preceding month;
      16% had a peak flow meter at home; and 7% had oral steroids available. Of the 44%
      of subjects with asthma, who could identify an exacerbation of asthma in the
      preceding 6 months: 19% had used a peak flow meter during the episode; 19% had
      changed their treatment without first being told to do so by a doctor; and 50%
      had sought urgent medical help. Smokers used less appropriate asthma management
      and subjects whose asthma had a severe impact on quality of life used more
      treatment and peak flow monitoring. In conclusion, the prevalence of asthma among
      adults in Greenwich, UK, has increased since a similar survey in 1986. Many
      people have fairly mild asthma and a smaller number have severe disease. Much
      remains to be done to promote appropriate strategies for self-management of
      asthma exacerbations.

PMID- 9192919
TI  - Allergen reduction measures in houses of allergic asthmatic patients: effects of
      air-cleaners and allergen-impermeable mattress covers.
AB  - Recommendations for allergen avoidance or allergen reduction measures play an
      important part in the treatment of allergic asthmatic patients. The purpose of
      this study was to test recently developed air-cleaners with respect to their
      capacity to capture airborne allergen particles and to improve clinical
      parameters of asthmatic patients sensitized to aeroallergens. Forty five allergic
      asthmatic patients were studied in a double-blind procedure for 6 months. The
      patients were divided into three groups of 15 patients. In Group 1, the
      intervention consisted of the application of active air-cleaners in living-rooms
      and bedrooms. In Group 2, placebo air-cleaners were used in combination with
      allergen-impermeable mattress covers. In Group 3, the same intervention was
      performed as in Group 2 but with active air-cleaners. Allergen levels in mattress
      and floor dust were measured before, and 3 and 6 months after the interventions.
      After 6 months, the air-cleaners were dismantled and the filters were analysed
      for the amount of dust collected and allergen content. Immunological and lung
      function parameters were measured before, and 3 and 6 months after the
      interventions. Considerable amounts of airborne dust and allergenic particles
      were captured in the filters of the air-cleaners. Up to the 18.9 g of dust, 4,513
      ng of house dust mite allergen, Der p 1, and 50,000 mU of cat allergen, Fel d 1,
      (in houses with cats) were collected by air-cleaners in living-rooms. Only in
      Group 3 (in which both active air-cleaners and mattress covers were used) was a
      small (less than 1 doubling dose) but statistically significant improvement of
      provocative concentration of histamine causing a 20% fall in forced expiratory
      volume in one second (PC20) observed (from 5.96 to 9.02 mg x mL(-1)). The amount
      of dust and house dust mite allergen collected in the filters was significantly
      correlated with an improvement of peak flow variation. In combination with other
      allergen avoidance measures, the examined air-cleaners can contribute to
      diminished allergen exposure and improvement of airway hyperresponsiveness in
      asthmatic patients.

PMID- 9192921
TI  - Users of antiasthma drugs in Iceland: a drug utilization study.
AB  - There has been an increasing consensus worldwide on how to treat asthma, and,
      simultaneously, an increase in the sales of antiasthma drugs. However, little is
      known about actual drug use, dosage, combinations of drugs, etc., or about the
      clinical characteristics of patients using these drugs. All individuals with
      prescriptions for antiasthma drugs, who came to Icelandic pharmacies during March
      1994, were invited to participate. By means of questionnaires, the pharmacists
      recorded the age and gender of the patient, the specialty of the prescribing
      doctor, as well as the name of the drug, total amount prescribed, and dosage. The
      patients were asked to answer another questionnaire on their clinical diagnosis,
      usage of other antiasthma drugs, etc. The pharmacists registered 2,026
      individuals, with 2,687 prescriptions: 1,574 for beta2-agonists, 838 for inhaled
      corticosteroids, 208 for theophylline, 48 for anticholinergic drugs, and 19 for
      cromoglycates. One thousand, three hundred and fifty one patients answered the
      questionnaires. The majority (67%) claimed to have asthma, 18% chronic
      bronchitis, 11% emphysema and 5% other diseases or symptoms. Among those aged >
      or = 16 yrs with asthma, 93% used beta2-agonists, 62% inhaled corticosteroids,
      19% theophylline, and very few used other drugs. The most commonly used
      combination (57%) was beta2-agonists with inhaled corticosteroids. Thirty one per
      cent used beta2-agonists as monotherapy, and 5% used only inhaled
      corticosteroids. Theophylline was used mainly in combination with beta2-agonists
      and inhaled corticosteroids. In conclusion, our data suggest that two thirds of
      antiasthma drug users have asthma and that most are treated according to present
      guidelines. The use of inhaled corticosteroids, however, seems somewhat less than
      optimal.

PMID- 9192922
TI  - Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired
      breath condensate of asthmatic patients.
AB  - Symptoms of bronchial asthma are a manifestation of airway inflammation.
      Circulatory leucocytes (predominantly eosinophils, mast cells and neutrophils),
      release inflammatory mediators, including reactive oxygen species, i.e.
      superoxide anion which is dismutated to hydrogen peroxide (H2O2). Neutrophils
      from asthmatics generate greater amounts of these species than those of healthy
      subjects. Some of the H2O2 and thiobarbituric acid-reactive products (TBARs) can
      evaporate from alveolar lining fluid, and could be expired from the airways of
      asthmatics. In this study, therefore, we determined whether asthmatic patients
      exhale more H2O2 and TBARs than healthy subjects. We examined 10 healthy subjects
      as a control group and 21 asthmatic subjects. In asthmatic subjects, forced
      expiratory volume in one second (FEV1), was 68+/-9% of predicted value, peak
      expiratory flow rate (PEFR) was 65+/-8% pred, and bronchial reversibility was
      34+/-5% of prebronchodilated FEV1. The mean H2O2 level measured
      spectrofluorimetrically in the expired breath condensate of asthmatic subjects
      was 26 fold higher than that in healthy controls (0.26+/-0.29 vs 0.01+/-0.03 nM;
      p<0.05). The concentration of TBARs in breath condensate was also higher in
      asthmatic patients compared with nonasthmatics (0.073+/-0.071 vs 0.004+/-0.009
      nM; p<0.05). There was a significant correlation between H2O2 level and
      concentration of TBARs in asthmatic patients (r=0.74; p<0.01). There was also a
      strong inverse correlation between H2O2 content of all asthmatics and FEV1% pred
      (r=-0.63; p<0.005) and PEFR% pred (r=-0.52; p<0.05). We conclude that there are
      elevated levels of hydrogen peroxide and thiobarbituric acid-reactive products in
      expired breath condensate of asthmatic patients, and that measurement of these
      substances in the expired breath condensate could be a simple, noninvasive method
      that could be used as a biochemical marker of airway inflammation.

PMID- 9192923
TI  - Peak flow variation in childhood asthma: relationship to symptoms, atopy, airways
      obstruction and hyperresponsiveness. Dutch CNSLD Study Group.
AB  - Although home recording of peak expiratory flow (PEF) is considered useful in
      managing asthma, little is known about the relationship of PEF variation to other
      indicators of disease activity. We examined the relationship of PEF variation,
      expressed in various ways, to symptoms, atopy, level of lung function, and
      airways hyperresponsiveness in schoolchildren with asthma. One hundred and two
      asthmatic children (aged 7-14 yrs) recorded symptoms and PEF (twice daily) in a
      diary for 2 weeks after withdrawal of all anti-inflammatory maintenance
      medication. PEF variation was expressed as amplitude % mean, as standard
      deviation and coefficient of variation of all recordings, and as low % best
      (lowest PEF as percentage of the highest of all values). Atopy and level of
      forced expiratory volume in one second (FEV1) % predicted were not significantly
      related to PEF variation. The provocative dose of histamine causing a 20% fall in
      FEV1 (PD20) and symptom scores were significantly, but weakly, related to PEF
      variation. The index, low % best, proved easy to calculate and effective in
      identifying a short-term episode of reduced PEF. We conclude that peak expiratory
      flow variation in children with stable, moderately severe asthma is
      significantly, but weakly, related to symptoms and airways hyperresponsiveness.
      These three phenomena, therefore, all provide different information on the actual
      disease state. Expressing peak expiratory flow variation as low % best is easy to
      perform and appears to be clinically relevant.

PMID- 9192924
TI  - Asthma self-management programmes in a population of Italian children: a
      multicentric study. Italian Study Group on Asthma Self-Management Programmes.
AB  - This study was designed to answer three main questions: 1) Does asthma self
      management education reduce asthma morbidity? 2) Are the two programmes "Living
      With Asthma" and "Open Airways" equally effective in doing so? 3) Is a shortened
      version of these programmes (4 weeks) as effective as the longer original
      programme (8 weeks)? Twelve Italian centres of paediatric bronchopneumology
      selected 312 children with asthma, who were stratified by disease severity,
      gender and age, and then randomly assigned to an Experimental group which
      received an educational programme or to a Comparison group, which did not. Of the
      312 children selected, 209 (114 Experimental and 95 Comparison) completed the
      educational protocol and a 1 year follow-up. Data recorded during the last 2
      months of follow-up, 10 months after the educational intervention, showed that
      the Experimental group required significantly fewer emergency treatments: this
      reduction was more evident in the more severe asthma cases. In the Experimental,
      but not in the Comparison group, patients with more severe asthma consumed more
      medications than patients with milder asthma "Open Airways" yielded, in some
      cases, better results than "Living with Asthma": but a type 2 error is possible.
      The standard and the shortened programmes proved equally effective. In
      conclusion, following education, regardless of receiving a short or long
      educational programme, asthma patients use emergency care services less and use
      medications more appropriately in comparison with standard care without
      education. This suggests that short educational programmes can be highly cost
      effective in children with asthma.

PMID- 9192925
TI  - Exercise performance in children with asthma: is it different from that of
      healthy controls?
AB  - Exercise tolerance and possible limitation in work capacity of asthmatic children
      is still a matter of debate. The aim of this study was to compare ventilation and
      gas exchange response to exercise of asthmatic children with that of healthy
      controls. Exercise performance was evaluated in 80 children with mild-to-moderate
      asthma, aged 7-15 yrs, and in 80 healthy controls matched for age, height, weight
      and habitual level of physical activity. The children performed a maximal
      exercise test on a treadmill, during which oxygen uptake (V'O2), carbon dioxide
      output (V'CO2) and minute ventilation (V'E) were measured continuously. No
      premedication was given to the asthmatic children. Forced expiratory volume in
      one second (FEV1) at rest was 93+/-11% of predicted in asthmatic children and
      95+/-9% pred in controls. After the run, the mean fall in FEV1 was 13.9% (range 0
      57%) and 1.6% (0-9%), respectively (p<0.001). The two groups achieved similar
      maximum oxygen uptake (V'O2,max) ((mean+/-SD) 40.3+/-8.4 and 42.6+/-9.6 mL x min(
      1) x kg(-1) in asthmatics and controls, respectively; NS) and maximum minute
      ventilation output (V'E,max) (42.9+/-14.8 and 45.7+/-14.9 L x min(-1)
      respectively; NS). The kinetics of V'O2, V'CO2 and V'E during the test revealed
      no differences between the two populations. Moreover, anaerobic threshold and
      oxygen pulse were the same in the two groups. Asthmatics showed a ventilatory
      pattern with lower respiratory frequencies and greater tidal volumes during the
      run. These results suggest that asthmatic children can achieve a level of
      exercise performance similar to that of healthy children, provided that they have
      a comparable level of habitual physical activity. The only difference found
      concerned the ventilatory pattern of the asthmatic children, which was
      characterized by a reduced respiratory frequency and greater tidal volume at the
      same minute ventilation. The level of physical conditioning was found to be the
      main determinant of exercise tolerance for children with controlled asthma.

PMID- 9192926
TI  - An evaluation of two aerosol delivery systems for rhDNase.
AB  - Increasingly, proteins are delivered to the respiratory tract as an aerosol, and
      clinical efficacy is dependent on optimal delivery of the protein in an intact
      form. The object of this study was to compare the in vivo and in vitro results of
      two aerosol delivery systems for the aerosolization of recombinant human
      deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients
      with CF who were to be initiated on rhDNase were randomized either to the Hudson
      nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the
      CR50 air compressor. An in vitro study was performed in six sets of the two
      aerosol delivery systems. One hundred and seventy three patients were randomized
      in this open study, where rhDNase was administered for 7 days. Improvements in
      pulmonary function were observed in both groups following 1 week of therapy with
      rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups,
      respectively, were: 16 and 11% for forced expiratory volume in one second
      (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced
      expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater
      proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in
      FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream
      nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for
      the aerosol mass produced (p<0.001), higher percentage of particles in the
      respirable range (p<0.001) and greater respirable output (p<0.005), compared to
      the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more
      efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in
      vivo study only suggested a difference. Clinically, the two systems have similar
      efficacy.

PMID- 9192927
TI  - Evaluation of a self-management plan for chronic obstructive pulmonary disease.
AB  - We hypothesized that the use of an Action Plan might assist self-management for
      patients with chronic obstructive pulmonary disease (COPD). A pilot process and
      randomized, controlled study were undertaken to evaluate an Action Plan that
      provided advice on management of usual care and exacerbations, together with a
      booklet on self-management. Fifty six subjects with COPD recruited through
      general practitioners (GPs) completed the 6 month study, 27 in the control group
      and 29 in the intervention group. The control group received usual care from
      their GP, and the intervention group received a booklet and Action Plan from
      their practice nurse plus a supply of prednisone and antibiotic from their GP.
      The two groups were demographically similar with a mean age of 68 yrs. The
      resources were well received by GPs, practice nurses and intervention group
      subjects. After 6 months, there were no differences in quality of life scores or
      pulmonary function. There were significant changes in self-management behaviour
      in the intervention group compared to controls. In response to deteriorating
      symptoms, 34 versus 7% (p=0.014) initiated prednisone treatment and 44 versus 7%
      (p=0.002) initiated antibiotics. Subjects in the intervention group readily
      adopted self-management skills but did not show any difference in quality of life
      or lung function parameters. A larger, prospective, controlled, clinical trial of
      this approach is warranted.

PMID- 9192928
TI  - Psychosocial predictors of long-term success of in-patient pulmonary
      rehabilitation of patients with COPD.
AB  - Studies of the long-term outcome of pulmonary rehabilitation have measured
      quality of life (QOL) mainly as disease-specific functional impairment, but long
      term effects on overall satisfaction with health or life have not yet been
      adequately evaluated. Furthermore, the influence of personality traits on the
      long-term outcome of pulmonary rehabilitation have not so far been examined. The
      following questions were studied: 1) What are the short- and long-term effects of
      a rehabilitation programme on lung function (forced expiratory volume in one
      second as percentage of predicted (FEV1 % pred)), on satisfaction with life
      (defined as quality of life), and on health satisfaction (HS)? 2) Are there
      physical or psychosocial predictors for the success of pulmonary therapy? In this
      prospective clinical study, baseline data (FEV1 % pred, arterial oxygen tension
      (Pa,O2), QOL, HS, dyspnoea, coping scales) were studied at entry (t1); follow-up
      on discharge (t2); and 1 yr after hospitalization (t3) in 54 consecutive patients
      (mean age 64 yrs) with chronic obstructive pulmonary disease (COPD). Complete
      data were obtained at follow-up on 32 subjects. FEV1 % pred improved from 42%
      (t1) to 52% (t2) (p<0.001) but dropped to 46% at t3 (t1-t3: p<0.05). QOL improved
      significantly during hospitalization but dropped to initial levels 1 yr after
      discharge. A significant increase in health satisfaction during hospitalization
      was maintained at follow-up. Improvements in lung function were greater in
      patients with higher QOL scores on entry; subjects with the greatest tendency to
      use wishful thinking as a coping strategy had less improvement. In conclusion,
      the effects of pulmonary rehabilitation on lung function and health satisfaction
      are positive and enduring. Quality of life and coping have an effect on the long
      term outcome of pulmonary rehabilitation, probably as expressions of patients'
      personality traits.

PMID- 9192929
TI  - Training with supplemental oxygen in patients with COPD and hypoxaemia at peak
      exercise.
AB  - Supplemental oxygen has acute beneficial effects on exercise performance in
      patients with chronic obstructive pulmonary disease (COPD). The purpose of this
      study was to investigate whether oxygen-supplemented training enhances the
      effects of training while breathing room air in patients with severe COPD. A
      randomized controlled trial was performed in 24 patients with severe COPD who
      developed hypoxaemia during incremental cycle exercise (arterial oxygen
      saturation (Sa,O2) <90% at peak exercise). All patients participated in an in
      patient pulmonary rehabilitation programme of 10 weeks duration. They were
      assigned either to general exercise training while breathing room air (GET/RA
      group: forced expiratory volume in one second (FEV1) 38% of predicted; arterial
      oxygen tension (Pa,O2) 10.5 kPa at rest; Pa,O2 7.3 kPa at peak exercise), or to
      GET while breathing supplemental oxygen (GET/O2 group: FEV1 29% pred; Pa,O2 10.2
      kPa at rest; Pa,O2 7.2 kPa at peak exercise). Sa,O2 was not allowed to fall below
      90% during the training. The effects on exercise performance while breathing air
      and oxygen, and on quality of life were compared. Maximum workload (Wmax)
      significantly increased in the GET/RA group (mean (SD) 17 (15) W, p<0.01), but
      not in the GET/O2 group (7 (25) W). Six minute walking distance (6MWD), stair
      climbing, weight-lifting exercise (all while breathing room air) and quality of
      life significantly increased in both groups. Acute administration of oxygen
      improved exercise performance before and after training. Training significantly
      increased Wmax, peak carbon dioxide production (V'CO2) and 6MWD while breathing
      oxygen in both groups. Differences between groups were not significant. Pulmonary
      rehabilitation improved exercise performance and quality of life in both groups.
      Supplementation of oxygen during the training did not add to the effects of
      training on room air.

PMID- 9192930
TI  - Mechanisms of worsening gas exchange during acute exacerbations of chronic
      obstructive pulmonary disease.
AB  - This study was undertaken to investigate the mechanisms that determine abnormal
      gas exchange during acute exacerbations of chronic obstructive pulmonary disease
      (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were
      studied after admission and 38+/-10 (+/-SD) days after discharge, once they were
      clinically stable. Measurements included forced spirometry, arterial blood gas
      values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2),
      and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas
      technique. Exacerbations were characterized by very severe airflow obstruction
      (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L,
      during exacerbation and stable conditions, respectively; p=0.01), severe
      hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction
      (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01)
      and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8
      kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during
      exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04)
      as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost
      negligible on both measurements. V'E remained essentially unchanged during
      exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/
      2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(
      1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly
      by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q'
      partially counterbalanced the effect of greater V'O2 on mixed venous oxygen
      tension (PV,O2). We conclude that worsening of gas exchange during exacerbations
      of chronic obstructive pulmonary disease is primarily produced by increased
      ventilation/perfusion inequality, and that this effect is amplified by the
      decrease of mixed venous oxygen tension that results from greater oxygen
      consumption, presumably because of increased work of the respiratory muscles.

PMID- 9192931
TI  - Sniff nasal inspiratory pressure in patients with chronic obstructive pulmonary
      disease.
AB  - In subjects with normal lung mechanics, inspiratory muscle strength can be
      reliably and easily assessed by the sniff nasal inspiratory pressure (SNIP),
      which is the pressure measured in an occluded nostril during a maximal sniff
      performed through the contralateral nostril. The aim of this study was to assess
      the validity of the SNIP in patients with chronic obstructive pulmonary disease
      (COPD), where pressure transmission from alveoli to upper airways is likely to be
      dampened. Twenty eight patients with COPD were studied (mean forced expiratory
      volume in one second (FEV1) = 36% of predicted). The SNIP and the sniff
      oesophageal pressure (sniff Poes) were measured simultaneously during maximal
      sniffs, and were compared to the maximal inspiratory pressure obtained against an
      occlusion (MIP). All measurements were performed from functional residual
      capacity in the sitting position. The ratio SNIP/sniff Poes was 0.80, and did not
      correlate with the degree of airflow limitation. The ratio MIP/sniff Poes was
      0.87, and the ratio SNIP/MIP was 0.97. Inspiratory muscle weakness, as defined by
      a low sniff Poes, was present in 17 of the 28 patients. A false diagnosis of
      weakness was made in eight patients when MIP was considered alone, in four when
      SNIP was considered alone, and in only three patients when MIP and SNIP were
      combined. We conclude that both the sniff nasal inspiratory pressure and the
      maximal inspiratory pressure moderately underestimate sniff oesophageal pressure
      in chronic obstructive pulmonary disease. Although suboptimal in this condition,
      the sniff nasal inspiratory pressure appears useful to complement the maximal
      inspiratory pressure for assessing inspiratory muscle strength in patients with
      chronic obstructive pulmonary disease.

PMID- 9192932
TI  - Is outcome from ARDS related to the severity of respiratory failure?
AB  - The characteristics and outcome of acute respiratory distress syndrome (ARDS) may
      have changed with time. Some studies have reported that mortality is more
      commonly related to the development of sepsis/multiple organ failure (MOF), and
      others that it is related to the severity of acute respiratory failure (ARF). The
      present study evaluates the relative importance of the two phenomena in a large
      series of patients. The clinical and biological data of all patients who
      developed ARDS during a 26 month period (January 1993 until February 1995) in our
      intensive care unit (ICU) were reviewed retrospectively. A total of 129 patients
      developed ARDS during the study period, representing an incidence of 2.4% of all
      ICU admissions. The mortality rate was 52%. The primary cause of death was
      sepsis/MOF (49%), followed by respiratory failure (16%), cardiac failure or
      arrhythmias (15%), neurological failure (10%), and other causes (8%). The
      mortality rate was related to age and degree of organ failure. MOF was not always
      a cause of late death, since half the deaths occurred within 5 days after
      admission. In addition, mortality was higher in septic than in nonseptic
      patients, and lower in trauma and surgical than in medical patients. We conclude
      that sepsis/multiple organ failure is still the most common cause of death in
      acute respiratory distress syndrome. Improvements in outcome of acute respiratory
      distress syndrome may depend more on treatment of sepsis and multiple organ
      failure than on oxygenation measures.

PMID- 9192933
TI  - Upper abdominal surgery: does a lung function test exist to predict early severe
      postoperative respiratory complications?
AB  - We evaluated the capacity to predict severe respiratory complications (SRCs)
      following upper abdominal surgery (UAS) by using the results of a respiratory
      questionnaire and preoperative pulmonary function tests. Lung volumes, flows and
      transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361
      consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h
      after UAS by clinical examination and chest radiography. Univariate and stepwise
      multiple logistic regression analyses were performed to estimate the odds ratio
      (OR) and 95% confidence interval (95% CI) of each single input variable, and to
      determine which indices best predicted outcome. These patients had a 1% mortality
      rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best
      predictors for SRCs by multiple analysis were: preoperative current
      hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV)
      (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values
      both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The
      algorithm thus obtained (logit theta) was extremely sensitive (84%), specific
      (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that
      preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to
      a lesser extent percentage predicted values both of forced expiratory volume in
      one second and transfer factor of the lung for carbon monoxide, have a
      significant predictive capacity for severe respiratory complications following
      upper abdominal surgery.

PMID- 9192934
TI  - Physiologically based indices of volumetric capnography in patients receiving
      mechanical ventilation.
AB  - Several indices of ventilatory heterogeneity can be identified from the
      expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims
      of this study were: 1) to analyse several computerizable indices of volumetric
      capnography in order to detect ventilatory disturbances; and 2) to establish the
      relationship between those indices and respiratory system mechanics in subjects
      with normal lungs and in patients with acute respiratory distress syndrome
      (ARDS), both receiving mechanical ventilation. We studied six normal subjects and
      five patients with early ARDS mechanically ventilated at three levels of tidal
      volume (VT). Respiratory system mechanics were assessed by end-expiratory and end
      inspiratory occlusion methods, respectively. We determined Phase III slopes,
      Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of
      alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as
      a function of expired volume. Differences between normal subjects and ARDS
      patients were significant both for capnographic and mechanical parameters.
      Changes in VT significantly altered capnographic indices in normal subjects, but
      failed to change ventilatory mechanics and VAE/VT in ARDS patients. After
      adjusting for breathing pattern, VAE/VT exhibited the best correlation with the
      mechanical parameters. In conclusion, volumetric capnography, and, specifically,
      the ratio of alveolar ejection volume to tidal volume allows evaluation and
      monitoring of ventilatory disturbances in patients with adult respiratory
      distress syndrome.

PMID- 9192935
TI  - Vital capacities in acute and chronic airway obstruction: dependence on flow and
      volume histories.
AB  - The aim of this study was to investigate whether measurements of vital capacity
      (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory)
      and by the rate of expiratory flow. The study was performed on 25 individuals
      with chronic airway obstruction (CAO) and a forced expiratory volume in one
      second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO
      group), and 10 asthmatic subjects with methacholine (MCh)-induced
      bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during
      fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from
      end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced
      (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the
      smallest volume (3.75+/-1.03 L) and significantly different from the other three
      estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly
      different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94
      L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference
      between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These
      data suggest that both flow and volume histories contribute to decreased vital
      capacities during bronchoconstriction. However, whereas increasing expiratory
      flow always tends to decrease vital capacity, the volume history of full
      inflation has different effects in chronic and acute bronchoconstriction,
      probably due to different effects on airway calibre. These results stress the
      importance of using standardized manoeuvres in order to obtain comparable values
      of vital capacity.

PMID- 9192936
TI  - Respiratory mechanics and morphometric changes during pneumoperitoneum in normal
      rats.
AB  - Pneumoperitoneum may give rise to several respiratory changes; nevertheless, no
      comprehensive analysis of respiratory mechanics has been performed under this
      condition. Respiratory mechanics and thoracoabdominal morphometry were evaluated
      in six sedated, anaesthetized, paralysed, and mechanically-ventilated rats before
      (control) and during pneumoperitoneum. After airway occlusion at end-inspiration,
      respiratory system, pulmonary, and chest wall resistive pressures (deltaP1,rs,
      deltaP1,L and deltaP1,cw, respectively) and viscoelastic/inhomogeneous pressures
      (deltaP2,rs, deltaP2,L and deltaP2,cw, respectively) were determined. Total
      pressure changes (deltaPtot) were calculated as the sum of deltaP1 and deltaP2,
      yielding the values of deltaPtot,rs, deltaPtot,L and deltaPtot,cw, respectively.
      Respiratory system, lung, and chest wall static (Est,rs, Est,L and Est,cw,
      respectively), and dynamic elastances (Edyn,rs, Edyn,L and Edyn,cw,
      respectively), and the corresponding changes in elastance (deltaE) (calculated as
      Edyn-Est) were also obtained. Chest wall configuration both at functional
      residual capacity (FRC) and end-inspiration (FRC + tidal volume (VT)) was also
      evaluated in another four rats. Pneumoperitoneum significantly increased
      deltaPtot,rs, deltaPtot,cw, deltaP2,rs, deltaP2,cw, deltaErs, deltaEcw, Est,rs,
      Est,L and Est,cw. Lateral and anteroposterior diameters increased significantly,
      with the exception of lateral diameters at the level of crista iliaca.
      Cephalocaudal diameter and FRC decreased. In conclusion, pneumoperitoneum
      augments elastances and increases the pressure dissipated against
      viscoelasticity/inhomogeneity of the respiratory system and chest wall. These
      changes are related to a cephalad displacement of the diaphragm plus changes in
      thoracoabdominal configuration.

PMID- 9192937
TI  - Increased risk of tuberculosis transmission in families with microepidemics.
AB  - In the present study, we analysed: 1) prevalence of TB infection and incidence of
      disease among family contacts of a cohort of patients with TB; 2) differential
      characteristics of families with microepidemics and families with < or = 1 new
      case of TB; and 3) efficacy of chemoprophylaxis in this group of contacts. Three
      thousand and seventy one family contacts of 635 patients with TB were studied.
      The study consisted of tuberculin skin testing and chest radiography in all
      cases, and bacteriological studies when active disease was suspected. Contacts
      were classified as belonging to: families with microepidemics (FME) (those with >
      or = 2 new cases of TB); families with one new case; and families with with no
      new cases. Chemoprophylaxis was prescribed in contacts following standard
      recommendations; all were followed up for 12-18 months. Rates of TB infection and
      disease among families, as well as the incidence of TB disease between those
      compliant and noncompliant with chemoprophylaxis were compared. Among the 3,071
      contacts, 1,264 (41%) were infected and 176 (6%) had TB. Twenty two families with
      FME (3%) yielded 55 new cases of TB. The prevalence of infection (excluding the
      TB cases) was 80% in families with FME, 52% in families with one new case, and
      41% in families with no new case (odds ratio (OR) 3.7; 95% confidence interval
      (95% CI) 2.1-6.5). Sputum smears were positive in 53% of cases in FME and 24% in
      non-FME families (OR 3.4; 95% CI 1.7-6.5). Bronchial sample cultures were
      positive in 84% of patients from FME families but in only 40% of those from non
      FME families (OR 7.5; 95% CI 3.6-15.8). Chemoprophylaxis was prescribed in 356
      contacts, of whom 296 complied and generated only one new case of TB, whilst
      there were 13 new cases among the 60 who did not comply (OR 81.6; 95% CI 26.7
      248.7). This study showed the prevalence of infection and incidence of
      tuberculosis among family contacts of patients with newly diagnosed tuberculosis
      to be very high. A small number of families with microepidemics accounted for
      most new cases of tuberculosis, which were also more infectious. The extremely
      high risk of transmission in these families, together with the proven efficacy of
      chemoprophylaxis, justifies prescription of chemoprophylaxis to all their
      members, regardless of age.

PMID- 9192938
TI  - Pneumothorax in HIV-infected patients: role of Pneumocystis carinii pneumonia and
      pulmonary tuberculosis.
AB  - Patients with acquired immune deficiency syndrome (AIDS) are at increased risk
      for pneumothorax, which usually occurs in the setting of Pneumocystis carinii
      pneumonia. The rationale of the present study was based on the hypothesis that
      the increased incidence of pulmonary tuberculosis in human immunodeficiency virus
      (HIV)-infected patients could favour the development of pneumothorax in such
      patients. A case-control study was performed comprising 140 HIV-infected patients
      grouped as follows: 35 patients with pneumothorax and 105 matched controls
      without pneumothorax. Univariate analysis identified four risk factors for
      pneumothorax: 1) previous P. carinii pneumonia (p=0.01); 2) current P. carinii
      pneumonia (p=0.02); 3) pulmonary tuberculosis (p=0.01); and 4) cysts,
      pneumatoceles or bullae on chest radiographs (p<0.001). Multivariate analysis
      indicated that current P. carinii pneumonia (p=0.01) and pulmonary tuberculosis
      (p=0.04) were both independent risk factors for pneumothorax. In conclusion, our
      findings demonstrate that, in addition to Pneumocystis carinii pneumonia,
      pulmonary tuberculosis enhances the risk of pneumothorax in patients with
      acquired immune deficiency syndrome.

PMID- 9192939
TI  - Induced sputum cell and fluid-phase indices of inflammation: comparison of
      treatment with dithiothreitol vs phosphate-buffered saline.
AB  - Treatment of sputum with dithiothreitol (DTT) gives reliable measurements of
      cellular and fluid-phase markers of airway inflammation. We investigated the
      extent to which DTT treatment influences these measurements as compared with
      phosphate-buffered saline (PBS). Hypertonic saline-induced sputum, collected from
      20 asthmatic subjects, was examined within 2 h. All portions which looked more
      solid (less fluid) than saliva were collected from the expectorate. The selected
      sputum was then divided into two portions: one treated with one volume of DTT and
      one volume of PBS, the other with two volumes of PBS. The filtrates were assessed
      blind for total and differential cell count, viability, and fluid-phase
      eosinophil cationic protein (ECP), fibrinogen, interleukin (IL)-5 and IL-8.
      Sputum treated with DTT compared with PBS had lower proportions of viable cells
      (median 66 versus 74%; p=0.003). In contrast, DTT-treated sputum had higher total
      cell counts (median 8.8 vs 2.8 x 10(6) mL(-1); p<0.001) and levels of ECP (median
      1340 vs 584 mg x L(-1); p<0.001) The measurements were similar with respect to
      the proportion of eosinophils, neutrophils, lymphocytes, macrophages, and fluid
      phase fibrinogen, IL-5 and IL-8. We conclude that dithiothreitol disperses cells
      more effectively and that this might account for the higher levels of eosinophil
      cationic protein. Dithiothreitol may affect cell viability, but the changes are
      not relevant with respect to cell counts. Additionally, dithiothreitol does not
      seem to influence the other measurements performed.

PMID- 9192940
TI  - Instrumental variability of respiratory blood gases among different blood gas
      analysers in different laboratories.
AB  - The aim of this study was to test the hypothesis that differences in oxygen
      tension (PO2) and carbon dioxide tension (PCO2) values from measurements
      performed on different blood gas analysers in different laboratories are
      clinically insignificant. Samples of fresh whole human tonometered blood (PO2 8.1
      kPa (60.8 mmHg); PCO2 5.3 kPa (39.9 mmHg)) were placed in airtight glass syringes
      and transported in ice-water slush. Blood gas analysis was performed within 3.5 h
      by 17 analysers (10 different models) in 10 hospitals on one day. The mean of the
      differences between the measured and target values was -0.01+/-0.19 and 0.21+/
      0.13 kPa (-0.06+/-1.45 and 1.55+/-1.01 mmHg) for PO2 and PCO2, respectively. The
      mean of the differences between two samples on one analyser was 0.06+/-0.06 and
      0.04+/-0.03 kPa (0.47+/-0.48 and 0.29+/-0.24 mmHg), respectively. For PO2 and
      PCO2 the interinstrument standard deviations (s(b)) were 0.18 and 0.13 kPa (1.38
      and 0.99 mmHg), respectively, whereas the intra-instrument standard deviations
      (s) were 0.06 and 0.03 kPa (0.47 and 0.26 mmHg), respectively. Both for PO2 and
      PCO2 the ratios of s(b)2 and s2 were statistically significant (analysis of
      variance (ANOVA) p<0.001). The standard deviations of a random measurement on a
      random analyser were 0.19 and 0.14 kPa (1.46 and 1.02 mmHg) for PO2 and PCO2,
      respectively. We conclude that the variability in measurement of blood gas values
      among different blood gas analysers, although negligible, depends much more on
      inter- than intra-instrument variation, both for oxygen tension and carbon
      dioxide tension. Technical improvements and adequate quality control programmes,
      including tonometry, may explain why the variability in blood gas values depends
      mainly on errors in the pre-analytical phase.

PMID- 9192942
TI  - A system to generate simultaneous forced oscillation and continuous positive
      airway pressure.
AB  - Assessment of airway obstruction in patients with obstructive sleep apnoea (OSA)
      subjected to continuous positive airway pressure (CPAP) may be carried out using
      the forced oscillation technique (FOT). To facilitate routine application of
      forced oscillation (FO) in sleep studies, our aim was to design a system capable
      of generating CPAP and applying FOT simultaneously. We constructed a prototype
      CPAP + FO generator by connecting a specially designed electromagnetic valve in
      parallel with a conventional blower. The capacity of the prototype to generate
      forced oscillation (5 Hz +/- 1 hPa) was tested by connecting it to a model
      simulating spontaneous breathing. The response of the prototype for target CPAPs
      of 5, 10 and 15 hPa and imposed sinusoidal breathing with peak flow up to 0.75 L
      x s(-1) was excellent when compared with that reported for commercially available
      CPAP generators. The applicability of the prototype was tested by applying it to
      assess airway obstruction in four patients with OSA during sleep. We conclude
      that the generator designed is able to apply continuous positive airway pressure
      and forced oscillation simultaneously. The system could be useful for automatic
      and noninvasive assessment of airway obstruction in patients with obstructive
      sleep apnoea subjected to continuous positive airway pressure. Future development
      of the generator may be helpful in implementing a set-up for automatic titration
      of continuous positive airway pressure.

PMID- 9192941
TI  - In vitro comparison of the amount of salbutamol available for inhalation from
      different formulations used with different spacer devices.
AB  - Metered-dose inhalers (MDIs) are currently being reformulated to contain
      hydrofluoroalkanes (HFAs), which do not damage the Earth's ozone layer. As
      different formulations of inhaled drugs may behave differently when used with
      spacer devices, we wished to determine the amount of salbutamol available for
      inhalation from a conventional metered-dose inhaler (Ventolin) and a new HFA
      containing formulation (Airomir), when used with two different spacers. A glass
      multistage liquid impinger was used to determine the amount of salbutamol
      delivered from the inhalers used with the Aerochamber and the Nebuhaler spacer
      devices. High speed video-recordings of inhaler actuation into air were made, and
      the speed of the aerosol and the aerosol cloud volume were measured. More
      salbutamol in small particles (<5 microm) was delivered from the Airomir MDI than
      the Ventolin MDI, when used with the Aerochamber (40.4 (95% confidence interval
      (95% CI) 31.2-49.6) versus 19.5 (19.0-20.0) microg) and the Nebuhaler (42.1 (36.3
      47.9) versus 24.6 (23.3-25.8) microg). The aerosol cloud from the Airomir MDI was
      slower than the Ventolin aerosol, and 60 ms after actuation had travelled 186 mm,
      whereas the Ventolin aerosol had travelled 320 mm. At the same time, the Airomir
      aerosol occupied a smaller volume than the Ventolin MDI (251 (213-288) versus 695
      (608-782) cm3). The hydrofluoroalkane formulation delivers more salbutamol than
      the conventional formulation when used either with the Aerochamber or Nebuhaler
      spacer. This may be because less drug is deposited in the spacer from the
      hydrofluoroalkane formulation, which is emitted from the metered-dose inhaler at
      a slower speed and occupies a smaller volume than the conventional formulation.
      The observed difference in drug delivery may be important for patients changing
      formulations, and in severe asthma, where high doses of salbutamol may be
      administered through a spacer.

PMID- 9192943
TI  - Lung involvement in the multisystem syndrome CHARGE association.
AB  - The CHARGE association is a multisystem syndrome, with a wide range of phenotypic
      expression, causing mortality, especially in childhood. We performed a hospital
      audit, in order to quantify the pulmonary implications, in 28 boys and 19 girls
      aged 0.02-23 yrs, with a definite diagnosis of CHARGE. A review of the records of
      these children with CHARGE association revealed that aspiration was common during
      infancy, as a result of inco-ordination of swallowing and gastro-oesophageal
      reflux. Aspiration was suspected in 22 of the 47 cases (47%), recurrent chest
      infections occurred in 22 cases (47%), and lung involvement contributed to 7 out
      of 17 deaths (41%). We conclude that respiratory morbidity and mortality is
      common in CHARGE, and decreases with age. Early diagnosis and treatment affords
      the best prognosis.

PMID- 9192944
TI  - Anti-Borrelia burgdorferi immunoglobulin seroprevalence in pulmonary sarcoidosis:
      a negative report.
AB  - The aetiology of sarcoidosis is still unknown. An infectious microorganism as
      causal agent for this disease could not be identified, but high titres of
      antibodies against Borrelia burgdorferi were detected in Chinese studies implying
      a causality with this disease. These findings, however, could not be reproduced
      by other researchers. The aim of this study was, therefore, to evaluate the
      possible role of these spirochetes in the pathogenesis of sarcoidosis by
      serological examinations. Sixty sera of patients suffering from sarcoidosis were
      examined for anti-B. burgdorferi immunoglobulin by enzyme-linked immunosorbent
      assay (ELISA). ELISAs for these antibodies show a high sensitivity, but a low
      specificity; therefore, a specific immunoblot was used to confirm positive
      results. Initially, 8% of the patients were reactive in the ELISA, and 20% of
      these could be confirmed by immunoblot. Therefore, the prevalence for B.
      burgdorferi antibodies in sarcoidosis patients was 1.6%. This result did not
      differ significantly from the prevalence of B. burgdorferi antibodies in 1,000
      regular blood donors of the city of Hamburg (7% reactive in the ELISA, 38%
      confirmed via immunoblot, prevalence 2.7%). The hypothesis of causality between a
      B. burgdorferi infection and sarcoidosis cannot be confirmed by this data.

PMID- 9192945
TI  - Acute severe asthma: pathophysiology and pathobiology of gas exchange
      abnormalities.
AB  - Acute severe asthma, or "status asthmaticus", is a devastating clinical condition
      ultimately resulting in life-threatening hypoxaemia. The pivotal intrapulmonary
      mechanism of this condition is profound ventilation/perfusion (V'A/Q') mismatch,
      characterized by a predominant bimodal blood flow pattern reflecting a marked
      deterioration (increase) of the dispersion of pulmonary blood flow. This V'A/Q'
      profile is consistent with the presence of numerous alveolar units with low
      V'A/Q' ratios, in which ventilation is markedly reduced, although never
      abolished, but perfusion is maintained. Further V'A/Q' worsening whilst breathing
      100% O2 suggests the presence of an underlying vigorous hypoxic vascular
      response. Of equal importance, gas exchange disturbances are poorly related to
      the severity of reduced maximal airflow rates. Inhaled platelet-activating factor
      (PAF), both in normal individuals and asthmatic patients, results in moderate-to
      severe disturbance of V'A/Q' status, a finding that is probably related to
      altered microvascular permeability within the airway wall. Salbutamol, but not
      ipratropium bromide, prevented all PAF-induced systemic and lung function
      abnormalities, possibly because venoconstriction in the bronchial circulation was
      antagonized. Taken together, these findings support the hypothesis that platelet
      activating factor may play a critical role in the pathobiology of severe acute
      exacerbations of asthma.

PMID- 9192946
TI  - Current aspects of spontaneous pneumothorax.
AB  - Although spontaneous pneumothoraces have been recognized and treated for almost
      180 yrs, new aspects have emerged concerning pathogenesis, diagnostic procedures
      and treatment modalities. In spite of the fact that blebs and bullae are
      frequently found in patients with primary spontaneous pneumothorax, they seldom
      seem to be the actual cause of the pneumothorax. Inflammatory changes in the
      distal airways play an important role in the occurrence of the pneumothorax
      during transpulmonary pressure changes. The value of the routine use of
      additional expiratory chest radiographs in diagnosing pneumothoraces has been
      doubted in previous studies. In this review, the diagnostic yield from additional
      expiratory chest radiographs is analysed. The role of previous pneumothoraces at
      presentation and the presence of blebs and bullae are discussed in predicting
      future recurrences and choosing appropriate treatment for optimal cost
      effectiveness. Recommendations are made regarding treatment of primary and
      secondary spontaneous pneumothorax.

PMID- 9192947
TI  - Genetic risk factors for chronic obstructive pulmonary disease.
AB  - Cigarette smoking is the major risk factor for chronic obstructive pulmonary
      disease (COPD). However, only a minority of cigarette smokers develop symptomatic
      disease. Studies of families and twins suggest that genetic factors also
      contribute to the development of COPD. We present a detailed literature review of
      the genes which have been investigated as potential risk factors for this
      disease. The only established genetic risk factor for COPD is homozygosity for
      the Z allele of the alpha1-antitrypsin gene. Heterozygotes for the Z allele may
      also be at increased risk. Other mutations affecting the structure of alpha1
      antitrypsin or the regulation of gene expression have been identified as risk
      factors. Genes, including those for alpha1-antichymotrypsin, alpha2
      macroglobulin, vitamin D-binding protein and blood group antigens, have also been
      associated with the development of COPD. Variants of the cystic fibrosis
      transmembrane regulator gene have been identified as risk factors for
      disseminated bronchiectasis. The genetic basis to chronic obstructive pulmonary
      disease has begun to be elucidated and it is likely that several genes will be
      implicated in the pathogenesis of this disease. The knowledge gained from such
      studies may also prove relevant to other inflammatory diseases.

PMID- 9192948
TI  - Cellular glutathione turnover in vitro, with emphasis on type II pneumocytes.
AB  - The most important extracellular antioxidant in the lung is glutathione (GSH).
      The epithelial lining fluid of normal lungs contains very high concentrations of
      this tripeptide, about 100 times higher than that found in the extracellular
      fluid of many other tissues. How these high extracellular GSH levels are
      established and the mechanisms for increases (e.g. smokers) or decreases (e.g.
      lung fibrosis) are still unknown, but more insight into the regulation of GSH
      turnover in type II pneumocytes has recently become available. The purpose of
      this review is to give an overview of the literature concerning cellular GSH
      turnover for different cell types in vitro, with an emphasis on alveolar type II
      epithelial cells. The main messages of this review are that: 1) GSH is, in fact,
      an important vehicle for stabilizing, detoxifying and transferring cysteine; 2)
      cysteine is the rate-limiting substrate for GSH synthesis, especially under
      conditions of oxidative stress; 3) various transport systems exist for the uptake
      of the constituents of GSH, of which gamma-glutamyltransferase appears to be
      important; 4) intracellular GSH levels of the type II cells are governed by
      different factors, including, probably, the extracellular redox state; and 5) a
      more reduced extracellular redox state appears to favour GSH efflux, whilst an
      oxidized state leads to retention of GSH inside the cell. These concepts should
      lead to reconsideration of some of the conventional approaches to increasing
      intracellular glutathione levels.

PMID- 9192949
TI  - Relief of sleep apnoea after treatment of acromegaly: report of three cases and
      review of the literature.
AB  - Sleep apnoea syndrome (SAS) is common in acromegalic patients. Occasionally, the
      relief of apnoeas after treatment of the acromegaly has been documented. We
      report the cases of three patients with acromegaly and severe obstructive sleep
      apnoea, who demonstrated a manifest improvement (respiratory disturbance index
      (RDI) <20) after treatment with octreotide, indicating that this drug may be
      effective in this disturbance. In one case, SAS disappeared although the growth
      hormone level was not fully normalized. This raises the intriguing hypothesis
      that octreotide has an effect on respiratory control or on the upper airway, that
      is not directly related to its action on production of growth hormone.

PMID- 9192950
TI  - Propylthiouracil-induced alveolar haemorrhage associated with antineutrophil
      cytoplasmic antibody.
AB  - Propylthiouracil (PTU) is known to cause vasculitis as a rare complication. We
      report the case of a patient who developed alveolar haemorrhage and haematuria
      whilst treated with PTU. The serum was positive for antineutrophil cytoplasmic
      antibody (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). All symptoms
      resolved completely after discontinuation of PTU. Alveolar haemorrhage or
      pulmonary-renal syndrome associated with antineutrophil cytoplasmic antibody with
      myeloperoxidase specificity may be a new complication of propylthiouracil
      therapy.

PMID- 9192951
TI  - Fatal acute pulmonary oedema after inhalation of fumes from
      polytetrafluoroethylene (PTFE).
AB  - The cases of three patients with acute pulmonary oedema caused by inhalation of
      fumes from heated polytetrafluoroethylene (PTFE) in a plastic factory are
      described. One patient died from profound hypoxaemia and shock shortly after
      admission, and the other two patients survived after medical treatment. This is
      the first report of fatal pulmonary oedema in a worker exposed to PTFE heated in
      a plastic extruding operation. From this observation, it appears that inhalation
      exposure to pyrolytic products from polytetrafluoroethylene can cause fatal
      respiratory complications. Special precautions are warranted in this kind of
      operation to prevent workers from being exposed to these substances.

PMID- 9192952
TI  - Dyspnoea, anorexia and weight loss in a 74 year old man.

PMID- 9192953
TI  - Measurement of lung volumes by plethysmography.

PMID- 9192954
TI  - It is time to consider standardizing the interrupter technique.

PMID- 9192955
TI  - Mini-Wright peak-flow meters are reliable after 5 yrs use.

PMID- 9192956
TI  - Potential clinical impact of normal-tissue intrinsic radiosensitivity testing.
AB  - A critical appraisal is given of the possible benefit from a reliable pre
      treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The
      considerations are in part, but not exclusively, based on the recent experience
      with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF2.
      Three strategies are reviewed: (1) to screen for rare cases with extreme
      radiosensitivity, so-called over-reactors, and treat these with reduced total
      dose, (2) to identify the sensitive tail of the distribution of 'normal'
      radiosensitivities, refer these patients to other treatment, and to escalate the
      dose to the remaining patients, or (3) to individualize dose prescriptions based
      on individual radiosensitivity, i.e. treating to isoeffect rather than to a
      specific dose-fractionation schedule. It is shown that these strategies will have
      a small, if any, impact on routine radiotherapy. Screening for over-reactors is
      hampered by the low prevalence of these among otherwise un-selected patients that
      leads to a low positive predictive value of in vitro radiosensitivity assays. It
      is argued, that this problem may persist even if the noise on current assays
      could be reduced to (the unrealistic value of) zero, simply because of the large
      biological variation in SF2. Removing the sensitive tail of the patient
      population, will only have a minor effect on the dose that could be delivered to
      the remaining patients, because of the sigmoid shape of empirical dose-response
      relationships. Finally, individualizing dose prescriptions based exclusively on
      information from a normal-tissue radiosensitivity assay, leads to a nearly
      symmetrical distribution of dose-changes that would produce a very small gain, or
      even a loss, of tumor control probability if implemented in the clinic. From a
      theoretical point of view, other strategies could be devised and some of these
      are considered in this review. Right now the most promising clinical use of in
      vitro radiosensitivity assays may be as a guide for the prescription of treatment
      schedules that are costly or involves a high risk of complications. Examples of
      this are certain strategies attempting to widen the therapeutic window, the use
      of very high doses or re-irradiation of a previously irradiated region, or the
      selection of patients for experimental strategies like the use of biological
      response modifiers to reduce normal-tissue toxicity. Finally, published data are
      summarized on the possible correlation between the radiosensitivities of tumor
      and normal tissues or between the sensitivities of various normal tissues.

PMID- 9192957
TI  - Short-term preoperative radiotherapy results in down-staging of rectal cancer: a
      study of 1316 patients.
AB  - BACKGROUND AND PURPOSE: This study was undertaken to investigate down-staging
      effects after short-term, high-fractionated preoperative radiotherapy. MATERIAL
      AND METHODS: The relationships between preoperative radiotherapy 25-25.5 Gy given
      over 5-7 days and clinical variables (sex, age, tumour level, metastatic disease,
      and tumour size) and the risk of lymph node metastases were examined in 1316
      patients with rectal adenocarcinoma by uni-, and multivariate analyses. RESULTS:
      Irradiated specimens contained smaller tumours (P < 0.00001) and nodal metastases
      were less common (P < 0.001). In a logistic regression model, tumour size in cm
      was positively related to the risk for nodal spread (odds ratio, OR = 1.14, 95%
      confidence limits, CL, of OR 1.08-1.22). In the same model, radiotherapy
      decreased the risk for nodal involvement (OR 0.73, 95% CL 0.58-0.92. This risk
      was particularly reduced when the time interval between start of radiotherapy and
      surgery equalled 10 days or more. CONCLUSIONS: These results demonstrate a down
      staging effect by a short course of preoperative radiotherapy which should be
      considered in the interpretation of radiotherapy trials and in the recruitment of
      patients for further postoperative adjuvant treatment.

PMID- 9192958
TI  - Radiotherapy of localised prostate cancer. Analysis of late treatment
      complications. A prospective study.
AB  - PURPOSE: To describe the late side-effects of radical radiotherapy of prostatic
      carcinoma and to analyse how pretreatment and treatment-related factors
      contribute to the toxicity. MATERIALS AND METHODS: 184 patients have regularly
      been followed after terminated radical external beam radiotherapy treatment (70
      Gy) for a mean of 46 (range 24-96) months. For registration of toxicity a
      modified RTOG scale was used. The Cox regression model was used for multivariate
      analysis. RESULTS: 37% of the patients had no late side-effects at all. Mild
      complications were reported by 53%, mainly gastrointestinal (42%) and urogenital
      (23%). A persistent improvement of the mild toxicity was seen in nearly half of
      the patients with gastrointestinal or nocturnal frequency side-effects. Only 16
      (9%) patients had moderate or severe complications. The multivariate analysis
      revealed that the risk of posttreatment complications was strongly correlated to
      pretreatment presence of symptoms from the organs at risk. Posttreatment
      complications presenting first 3 years after irradiation were rare. CONCLUSIONS:
      Radical external beam radiotherapy (70 Gy) can be given with a low risk of severe
      complications. It appears reasonable to assume that the risk can be further
      reduced by excluding patients with gastrointestinal and urinary tract disease or
      symptoms.

PMID- 9192959
TI  - Carcinoma of the cervical stump: retrospective analysis of 77 cases.
AB  - BACKGROUND AND PURPOSE: Although supracervical hysterectomy is becoming a rare
      procedure, there are still many women with retained cervical stump. The purpose
      of this retrospective study was to assess the results of treatment in patients
      with carcinoma of the cervical stump. MATERIALS AND METHODS: From 1974 to 1990,
      77 patients were treated for an infiltrating carcinoma of the cervical stump.
      This group accounted for 6.6% of the cervical carcinoma diagnosed during the same
      period. The pathological examination showed, 91% of squamous cell carcinomas and
      9% of adenocarcinomas. FIGO stage distribution was: I (35%), II (45%), III (18%),
      IV (2%). According to the stages, the treatment used a combination of external
      beam radiation therapy (EBRT) with plesiobrachytherapy (PBT), and in a few cases,
      patients underwent surgery or interstitial brachytherapy (IBT). In patients with
      bulky tumour or advanced stage and/or lymphatic node involvement, EBRT was first
      delivered. Most of Stage I and Stage II patients, began their treatment with PBT.
      All stages included, 95% of the patients were treated by exclusive radiation
      therapy. Complications were classified according to the recommendations of late
      effects normal tissues (LENT) scoring system described by the EORTC/RTOG.
      RESULTS: Three-year pelvic control was achieved in 59 of 77 patients (76.6%) in
      the whole series. Three-year pelvic control probabilities were 77% (95% CI: 66
      85%), and 89% (95% CI: 72-96%), 73.7% (95% CI: 65-88%) and 56% (95% CI: 28-80%)
      in the whole series and in Stage I-III tumour patients, respectively. The 5-year
      and 10-year overall survival probabilities in the whole series, were 66.4% (95%
      CI: 55-76%) and 61.2% (95% CI: 50-72%), respectively. Ten patients (12.8%)
      developed 17 late complications distributed as follows: G1, nine patients
      (11.7%); G2, five patients (6.5%); G3, one patient (1.3%); and G4, two patients
      (2.6%). CONCLUSIONS: Treatment results are similar both in patients with
      carcinoma of the cervical stump and in patients with carcinoma of the intact
      uterus. Indeed, it is sometimes difficult to perform a correct PBT application
      because of the pelvic anatomic modifications induced by the subtotal hysterectomy
      and its consequences on the new organisation of critical organs into the treated
      volume.

PMID- 9192960
TI  - Is post-operative radiation for renal cell carcinoma justified?
AB  - PURPOSE: To identify the pattern of failure in patients with resected renal cell
      carcinoma (RCC). MATERIALS AND METHODS: The records of 116 patients with
      unilateral, non-hematogenous metastatic RCC who were treated with definitive
      surgery and referred to the Ottawa Regional Cancer Centre between 1977 and 1988
      were reviewed. Distribution by stage included T1 (3 patients), T2 (42 patients)
      and T3 (71 patients). The median follow-up was 44 months, with a range of 4-267
      months. RESULTS: Local regional failure (LRF) developed in 8 patients. Nine
      patients developed local or regional recurrence, plus distant failure. Fifty
      eight patients had distant metastases (DM) only. The 7-year actuarial rate for
      LRF and DM were 12%, and 67%, respectively. The overall 7-year actuarial survival
      rate was 35%, and cause-specific survival was 42%. CONCLUSIONS: LRF alone is rare
      following nephrectomy. DM is the main pattern of failure. This data does not
      support the role of adjuvant radiation therapy in this disease.

PMID- 9192961
TI  - Endocrine profiles after radiotherapy in stage I seminoma: impact of two
      different radiation treatment modalities.
AB  - BACKGROUND AND PURPOSE: In patients with stage I seminoma treated with elective
      lymph node irradiation, testicular scatter doses are often thought to be
      responsible for later disturbances in fertility. We studied the influence of
      radiation field extensions and testicular doses on hormonal function. MATERIALS
      AND METHODS: FSH (follicle stimulating hormone) and LH (luteinizing hormone) were
      evaluated before radiotherapy (RT) and by serial analyses after treatment for 4
      years. Twenty-three patients were irradiated by hockey stick fields with a mean
      dose of 31.9 Gy (+/-4.7 SD) and a mean scatter dose of 54 8 cGy (+/-16.6 SD).
      Twenty-one patients received limited RT to the paraaortic nodes with 28.1 Gy (+/
      2.4 SD). The mean testicular dose was only 25 cGy (+/-7.8 SD). All patients had
      normal pre-treatment hormonal values. RESULTS: Six months after the end of RT,
      mean FSH values were significantly elevated in the hockey stick group (P =
      0.032), returning to normal after 3 years. The increase in LH was also
      significant, but stayed within normal ranges. Limited RT resulted in a minimal,
      dose-dependent increase of FSH; no changes in LH were noted. CONCLUSIONS: In
      patients with a normal hormonal status after semicastration, FSH is a reliable
      monitor for transient radiation-induced effects. To avoid treatment-related
      disturbances in spermatogenesis, scatter doses should be reduced to less than 20
      cGy.

PMID- 9192962
TI  - Hypofractionated radiotherapy for invasive bladder cancer.
AB  - BACKGROUND AND PURPOSE: The policy of the Radiotherapy Department of St. Thomas'
      Hospital in London for patients with invasive bladder cancer, used to be
      treatment with hypofractionated radiotherapy. The advantages of this
      fractionation scheme included reduction of the number of treatment sessions and
      better use of limited resources. Our results after hypofractionation were
      compared to series with more conventional radiotherapy. MATERIAL AND METHODS:
      Between 1975 and 1985, 123 patients with a T2-T3 transitional cell carcinoma of
      the bladder were treated by a radical course of hypofractionated radiotherapy.
      Local control, survival and morbidity rates were analysed retrospectively.
      RESULTS: The actuarial local control rates at 5 and 10 years were 31 and 29%,
      respectively. The actuarial cancer-specific 5- and 10-year survival rates were 48
      and 39%, respectively. Acute side effects were observed in 87% of patients. The
      actuarial overall and severe late complication rates at 5 years were 33 and 9%,
      respectively. The local control, survival and early side effect rates we found,
      were in the same range as those reported in literature. Late radiation side
      effects however, were more common after hypofractionated radiotherapy compared to
      conventional radiotherapy schedules. CONCLUSIONS: We conclude that the potential
      advantage of a reduced number of treatment sessions may be lost in the long term,
      because of the higher incidence of late morbidity after hypofractionated
      radiotherapy. Hypofractionation however, remains a valuable technique for
      palliation and deserves further investigation for radical treatment where access
      to equipment is difficult or resources are limited.

PMID- 9192963
TI  - Hypofractionated radiotherapy for muscle invasive bladder cancer in the elderly.
AB  - BACKGROUND AND PURPOSE: We have retrospectively investigated a hypofractionated
      regimen in a cohort of 65 elderly patients (median age 78 years), designed to
      minimise acute radiation affects and maximise patient tolerance and convenience
      in this frail group. MATERIALS AND METHODS: All patients were CT planned to a
      small volume. Once weekly fractions (6 Gy) prescribed to the 100% isodose as a
      target minimum to 30 Gy (n = 53) and 36 Gy (n = 12) were administered. Palliation
      of symptoms before, during, and 1 month from completion of radiotherapy were
      graded using the urinary and bowel symptom and toxicity index. RESULTS: Fifty
      five patients had persisting urinary symptoms following trans urethral resection
      of bladder. Twenty-eight (51%) were completely palliated of symptoms and 7 (13%)
      noticed an improvement at a 1 month review. Ninety-two percent of patients with
      haematuria were completely palliated compared to only 24% of those with dysuria
      and frequency. The median symptom free interval was 7 months (range 2-40months).
      Median overall survival was 9 months (range 2-41months). Twelve percent of
      patients required inpatient admission and only three failed to complete the
      prescribed course due to bowel toxicity. Grade 3 acute urinary and bowel
      treatment related toxicity, were recorded in 18% and 9% of patients,
      respectively. In total, 43% of patients noticed a transient worsening of their
      presenting symptoms on treatment. To date no significant late toxicity (>grade 2)
      has been recorded. CONCLUSIONS: This regimen is generally well tolerated and
      offers reasonable palliation of symptoms on an outpatient basis for this frail
      poor prognosis group. Haematuria is particularly well palliated although only a
      quarter of patients presenting with dysuria and frequency were rendered symptom
      free.

PMID- 9192964
TI  - Dose response relationship and multiple dose efficacy and toxicity of samarium
      153-EDTMP in metastatic cancer to bone.
AB  - INTRODUCTION: The optimal dose of samarium-153-EDTMP (153Sm-EDTMP) for effective
      palliation of painful metastases to bone is under investigation. It is not known
      whether increased doses of 153Sm EDTMP will lead to better and longer pain and
      tumour control and survival. Multiple dose efficacy and toxicity is of importance
      as most Patients will require prolonged support for pain. METHODS: Twenty-eight
      (28) patients were treated with 0.75 mCi/kg, 35 patients with 1.5 mCi/kg and 19
      patients with 3 mCi/kg in three sequential Phase I-II trials. Multiple doses were
      given to patients on the 0.75 mCi/kg and 1.5 mCi/kg dose levels. RESULTS: At all
      dose levels adequate pain control was achieved in 78-95% of patients. The
      duration of pain control was 40-56 days with the best results in the 1.5 mCi/kg
      group (56 days). There is no evidence that increasing dose leads to better and
      longer pain control, tumour response and survival, but toxicity is increased.
      Multiple doses can be given with acceptable toxicity and pain control, however,
      only 38% of patients will qualify for multiple treatments. CONCLUSION: 153Sm
      EDTMP provides adequate and safe palliation but multiple doses can only be given
      in 38% of patients. There is not a clear dose-response relationship. The length
      of pain control is satisfactory but not ideal and hospitalisation for 4 days
      every 6-8 weeks is a disadvantage. Further research is required to combine 153Sm
      EDTMP with cytostatics and to administer it on an out patient basis.

PMID- 9192965
TI  - In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with
      acute radiation toxicity in patients with head and neck cancer.
AB  - BACKGROUND AND PURPOSE: There is a considerable hope among clinicians and
      radiobiologists to detect genetically radiosensitive patients prior to
      radiotherapy. A predictive assay would enable adjustment of the total irradiation
      dose to the individual at a constant risk of normal tissue complications. In this
      prospective study, the clonogenic survival assay for primary human fibroblasts to
      determine radiosensitivity in vitro was evaluated and then correlated with
      clinically observed acute radiation reactions. MATERIALS AND METHODS: One hundred
      twenty-five independent survival experiments with primary fibroblasts derived
      from 63 biopsies from 55 cancer and non-cancer patients were performed. RESULTS:
      A wide variation of cell survival between biopsies was detected. Statistical
      analysis revealed a highly significantly larger interindividual than
      intraindividual variation of SF2 values. However, a considerable scatter of SF2
      values in repeated experiments was observed in individual cases. Age, gender,
      disease status (cancer patient, non-cancer patient) and origin of fibroblasts
      (skin, periodontal tissue) were demonstrated not to be statistically significant
      confounding factors on the intrinsic radiosensitivity in vitro. In a prospective
      study, no correlation of the SF2 and acute reactions in 25 patients with head and
      neck cancer treated with a primary accelerated radiochemotherapy was detected.
      CONCLUSION: Our data show that the clonogenic assay is able to distinguish
      between intrinsic radiosensitivities of primary human fibroblasts if a
      statistical approach is used but does not predict acute radiation toxicity.

PMID- 9192966
TI  - The impact of complex chromosomal rearrangements on the detection of
      radiosensitivity in cancer patients.
AB  - BACKGROUND AND PURPOSE: Lymphocytes of a small fraction of cancer patients
      responded to in vitro irradiation with an extreme chromosomal reaction. A large
      portion of the observed chromosome aberrations were complex chromosomal
      rearrangements (CCR). The present study is an attempt to define the impact of CCR
      on the predictive detection of an intrinsic clinical radiosensitivity in cancer
      patients in more detail. MATERIALS AND METHODS: A three-colour 'FISH-painting'
      technique (chromosome in situ suppression (CISS) hybridization) was used for the
      detection of chromosomal rearrangements, induced by in vitro irradiation, in 81
      samples of peripheral blood lymphocytes from 66 cancer patients. Thirty-three of
      those were assigned for radiation therapy, the others having just undergone
      radiation therapy. Seven healthy individuals served as controls. RESULTS: CCRs
      are a very rare event in non-irradiated cells. Lymphocytes of patients who had
      just undergone therapeutic irradiation, however, not only exhibited high basic
      frequencies of CCR but also responded to in vitro irradiation with a more drastic
      increase of CCR than did the lymphocytes of non-exposed patients. A high inter
      individual variability of the reaction to in vitro irradiation could be generally
      stated. The lymphocytes of patients with clinical signs of an outstanding
      radiosensitivity responded with an unusually high frequency of CCR. The total
      number of CCRs detected by CISS was found to be dependent on the interval from a
      previous radiation therapy and was slightly influenced by previous cytostatic
      therapy. Irrespective of these influences, patients with clinically defined
      radiation hypersensitivity were those with the highest radiosensitivity also in
      cytogenetic terms (including CCR). CONCLUSION: The successful use of FISH
      painting for the detection of CCR, in addition to the general breakage frequency,
      highlights its suitability in the identification of individual hypersensitivity
      to ionizing radiation. The time-consuming cytogenetic examination can be
      considerably reduced by its use.

PMID- 9192968
TI  - Continuous, pulsed or single acute irradiation of a transplanted rodent tumour
      model.
AB  - BACKGROUND: Recent advances in remote afterloading pulsed mode brachytherapy have
      provided a much needed tool for the radiation oncologist. It has the versatility
      of optimised physical dose distribution along with improved staff radiation
      protection and patient nursing. PURPOSE: This preliminary study was designed to
      explore the radiobiological equivalence between conventional continuous low dose
      rate tumour irradiation (CLDR) and the new technique of pulsed dose irradiation
      (PDR). MATERIALS AND METHODS: Subcutaneous isogenic sarcomas transplanted in
      female John's Strain Wistar rats were irradiated locally with acute, pulsed or
      continuous interstitial low dose-rate exposures at 9-11 mm mean diameter.
      RESULTS: As expected, single acute doses (5-40 Gy) were more effective (P < 0.01)
      in achieving tumour growth delay (1.4 days/Gy) than CLDR exposure (4-51 Gy) over
      24-48 h (0.93 days/Gy). However, PDR treatment (8 hourly fractions/day) at high
      dose-rate (8-48Gy) over 8-72 h was significantly (P = 0.01) more effective (1.66
      days/Gy) than CLDR but not acute exposures. CONCLUSIONS: These data suggest that,
      clinically a significantly improved therapeutic ratio may also be achievable with
      pulsed high dose rate brachytherapy, and that further radiobiological studies
      with in-vivo tumour models are needed.

PMID- 9192967
TI  - SN-38, a metabolite of the camptothecin derivative CPT-11, potentiates the
      cytotoxic effect of radiation in human colon adenocarcinoma cells grown as
      spheroids.
AB  - BACKGROUND AND PURPOSE: CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino]
      carbonyloxycamptothecin) is anew semisynthesized derivative of camptothecin. SN
      38 (7-ethyl-10-hydroxycamptothecin), a metabolite of CPT-11, plays a key role in
      the action of CPT-11. MATERIALS AND METHODS: To determine whether SN-38
      potentiates the cytotoxic effect of radiation, we investigated the interaction of
      SN-38 and radiation in vitro in monolayer cultures and multicellular spheroids of
      HT-29 human colon adenocarcinoma cells. RESULTS: HT-29 spheroids were more
      resistant to both SN-38 and irradiation than monolayer cells. SN-38 at a
      concentration of 2.5 microg/ml, which by itself was not cytotoxic, greatly
      increased the lethal effects of radiation in spheroids, but not in monolayer
      cultures. Exposure to SN-38 following irradiation inhibited the potentially
      lethal damage repair (PLDR) in spheroids. It is suggested that the mechanism of
      the radiosensitization by SN-38 is due to the PLDR inhibition. CONCLUSIONS: These
      results indicate that CPT-11 may play a role as radiosensitizer and that a
      combination of CPT-11 and irradiation could prove to be a particularly effective
      strategy with which to treat human colon adenocarcinoma.

PMID- 9192969
TI  - Lack of influence of sequence of top-up doses on repair kinetics in rat spinal
      cord.
AB  - BACKGROUND AND PURPOSE: The rat spinal cord model was used to determine whether
      repair kinetics changed during a course of fractionated radiotherapy if twice
      daily doses were given either at the initial or final period of a concomitant
      boost irradiation schedule. MATERIALS AND METHODS: The rat cervical spinal cord
      was irradiated from C2-T2 in 870 animals with top-up doses of three daily
      fractions of 9 Gy representing 75% of the biologic dose at the ED50 level for
      white matter necrosis. To simulate concomitant boost protocols, these top-up
      doses were given either preceding (initial top-up) or following (final top-up) a
      b.i.d. schedule of 1 Gy/F delivered at 0, 1, 2, 4, 8 or 24 h interfraction
      intervals. The end point was forelimb paralysis secondary to white matter
      necrosis. RESULTS: For interfraction intervals of 0, 1, 2, 4, 8 and 24 h, the
      initial top-up schedules yielded ED50 values of 18.2, 19.2, 23.7, 21.3, 27.2 and
      29.7 Gy, respectively; the corresponding ED50s from the final top-up schedules
      were 17.5, 19.0, 20.7, 21.2, 26.9 and 30.3 Gy, respectively. A 10% reduction in
      the ED50 value from pooled data was observed when the interfraction interval was
      reduced from 24 (ED50 = 30.3 Gy) to 8 h (ED50 = 27.1 Gy). Fitting the incomplete
      repair (IR) version of the LQ model with mono-exponential repair kinetics gave
      alpha/beta values of 1.4 and 1.5 Gy, and similar repair half-times of 4.3 and 5.0
      h for the initial and final top-up experiments, respectively. The IR model with
      bi-exponential repair kinetics did not provide a better fit to the data.
      CONCLUSIONS: We conclude that the sequence of top-up doses has no apparent
      influence on radiation sensitivity or repair kinetics in the rat spinal cord. The
      clinical implication is that the interfraction interval but not the timing of the
      boost is a critical determinant of spinal cord tolerance in concomitant boost
      protocols.

PMID- 9192970
TI  - Determination of 3D dose distribution from intracavitary brachytherapy of
      cervical cancer by MRI of irradiated ferrous sulphate gel.
AB  - BACKGROUND AND PURPOSE: MRI ferrous sulphate gel dosimetry has proven to be a
      valuable method for assessment of dose delivered in teletherapy. The intention of
      this study was to investigate ferrous sulphate gel as a possible dosimeter for
      intracavitary brachytherapy applications. MATERIALS AND METHODS: A plastic
      duplicate of a cervix ring applicator set was submerged in Fe2(+)-infused gelatin
      gel. The gel was subsequently irradiated by a stepwise moving 192Ir source, using
      automatic afterloading equipment (Microselectron, Nucletron-Oldelft International
      BV, Veenendaal, The Netherlands). A 3D dose distribution was reconstructed from
      MR images of the gel. RESULTS: The gel dose measurements were found to be of the
      same accuracy as TLD measurements. Isodose curves based on gel dosimetry and
      isodose curves computed by a dose planning system were generally less than 2 mm
      apart. MR images showing the position of the applicator set in a patient during
      treatment were used to obtain images describing patient anatomy in the sagittal
      and ring planes of the applicator set. Isodose curves computed from the gel
      measurements were then superimposed on these images, illustrating one possible
      way of linking dosimetrical and anatomical data. CONCLUSIONS: Our study shows
      that MRI ferrous sulphate gel dosimetry is a useful tool for studies of dose
      distributions in brachytherapy and their relation to critical organs. Possible
      improvements of the gel dosimeter lie in reducing the diffusion of ferric ions
      and increasing the radiation sensitivity of the gel.

PMID- 9192971
TI  - Granulocyte-macrophage colony-stimulating factor mouthwashes improve radiation
      induced mucositis in AIDS patients.

PMID- 9192972
TI  - Continuous infusion of macrophage inflammatory protein MIP-1alpha enhances
      leucocyte recovery and haemopoietic progenitor cell mobilization after
      cyclophosphamide.
AB  - Macrophage inflammatory protein 1alpha (MIP-1alpha) inhibits haemopoietic stem
      cell proliferation. This property has been exploited in a murine chemotherapy
      model and has been shown to ameliorate cytotoxic-induced myelosuppression after S
      phase-specific cytotoxic therapy. We have now shown that BB-10010, a stable
      mutant of MIP-1alpha, (a) is more effective when administered as a continuous
      infusion than when bolus injected and (b), when administered via a 7-day infusion
      during and after cyclophosphamide treatment, results in an earlier recovery of
      leucocyte numbers. This effect was accompanied by progenitor cell mobilization
      into the peripheral blood and included primitive cells with marrow-repopulating
      ability (MRA). Maximal mobilization and recovery of leucocytes occurred when MIP
      1alpha was combined with granulocyte colony-stimulating factor (G-CSF) therapy.
      The findings suggest that MIP1-alpha used alone or in combination with G-CSF may
      allow delivery of a greater chemotherapy dose intensity as a consequence of both
      accelerated leucocyte recovery and maintenance of high-quality mobilized
      progenitor cells for harvesting and peripheral blood stem cell transplantation.

PMID- 9192973
TI  - A comet assay of DNA damage and repair in K562 cells after photodynamic therapy
      using haematoporphyrin derivative, methylene blue and meso
      tetrahydroxyphenylchlorin.
AB  - Single-cell electrophoresis (comet assay) has been used to evaluate DNA damage
      and repair in the human myeloid leukaemia cell line K562 after low-dose
      (predominantly sub-lethal) treatments of hyperthermia and photodynamic therapy
      (PDT). Three different photosensitizers were examined: haematoporphyrin
      derivative (HpD), methylene blue (MB) and meso-tetrahydroxyphenylchlorin (mTHPC).
      None of the drugs in the absence of light, nor in light alone, resulted in
      detectable DNA damage. However, a significant amount of DNA damage was detected
      immediately after treatment with haematoporphyrin derivative or methylene blue
      PDT compared with drug-only or light-only treatments; no residual level of DNA
      damage was evident for either drug following a 4-h post-treatment incubation at
      37 degrees C. No significant DNA damage was detected after meso
      tetrahydroxyphenylchlorin PDT or hyperthermia either immediately or 4 h after
      treatment. We conclude that the alkaline comet assay can be applied as an
      effective screening assay for DNA damage induced by a range of laser therapies.

PMID- 9192974
TI  - Increased growth and incidence of lymph node metastases due to the angiogenesis
      inhibitor AGM-1470.
AB  - Using the rat tumour cell line LY80, a subline of Yoshida sarcoma, the effects of
      AGM-1470 on the growth of primary tumour and the incidence of regional lymph node
      metastasis were evaluated. AGM-1470 (30 mg kg(-1)) was administered
      subcutaneously or intravenously. Subcutaneous (s.c.) and intravenous (i.v.)
      injections were repeated for 8 days and 7 days respectively. Tumour growth of a
      primary region tended to be suppressed by AGM-1470. The s.c. tumours after
      sacrifice were much smaller in the AGM-1470-treated group (s.c. injection) than
      in the control groups. However, the growth of metastatic foci in the lymph nodes
      was prompted markedly by AGM-1470. All six of the AGM-1470-treated rats had
      developed swollen axillary lymph nodes and/or brachial lymph nodes on day 19
      after tumour implantation (the 7th day after the last treatment) compared with
      one of six saline-injected rats and three of six vehicle-alone treated rats with
      swollen axillary lymph nodes. The weight of lymph nodes after sacrifice in the
      AGM-1470-treated rats was much heavier than that of the other two groups.
      Histological examination showed that in the AGM-1470-treated group, the cortex
      and the medulla of the axillary lymph nodes were almost entirely replaced by
      tumour cells while, in the vehicle alone group, a notable hyperplasia of the
      lymph nodes due to BT cell proliferation tended to be induced. In the saline
      group, although a slight hyperplasia of lymph nodes was observed, there were only
      a few lymph node metastases. In the case of i.v. injection of AGM-1470, similar
      results were obtained. It is thought that LY80 cells spread to regional lymph
      nodes at a comparatively early stage by some change or other in which AGM-1470
      participated. From the present experiment, it is concluded that application of
      AGM-1470 alone to patients should be carried out with great caution.

PMID- 9192975
TI  - Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive
      and -resistant tumour cells.
AB  - In this study, the mechanism(s) by which heat increases cis
      diamminedichloroplatinum (cisplatin, cDDP) sensitivity in cDDP-sensitive and 
      resistant cell lines of murine as well as human origin were investigated. Heating
      cells at 43 degrees C during cDDP exposure was found to increase drug
      accumulation significantly in the cDDP-resistant cell lines but had little effect
      on drug accumulation in the cDDP-sensitive cell lines. DNA adduct formation,
      however, was significantly increased in all cell lines studied. Furthermore,
      ongoing formation of platinum (Pt)-DNA adducts after the end of cDDP treatment
      was enhanced and/or adduct removal was decreased in heated cells, resulting in
      relatively more DNA damage remaining at 24 h after the end of cDDP exposure.
      Correlation plots with survival revealed weak correlations with cellular Pt
      accumulation (r2 = 0.59) and initial Pt-DNA adduct formation (r2 = 0.64). Strong
      correlations, however, were found with Pt-DNA adducts at 6 h (r2 = 0.97) and 24 h
      (r2 = 0.89) after the incubation with the drug. In conclusion, the mechanism by
      which heat sensitizes cells for cDDP action seems to be the sum of multiple
      factors, which comprise heat effects on accumulation, adduct formation and adduct
      processing. This mechanism did not seem to differ between cDDP-sensitive and 
      resistant cells, emphasizing the potential of hyperthermia to reduce cDDP
      resistance.

PMID- 9192976
TI  - Proliferation, migration and invasion of human glioma cells exposed to paclitaxel
      (Taxol) in vitro.
AB  - Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested
      for its anti-migrational, anti-invasive and anti-proliferative effect on two
      human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour
      spheroids. In addition, the direct effect of paclitaxel on glioma cells was
      studied using flow cytometry and scanning confocal microscopy. Both cell lines
      showed a dose-dependent growth and migratory response to paclitaxel. The GaMg
      cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells.
      Paclitaxel also proved to be remarkably effective in preventing invasion in a co
      culture system in which tumour spheroids were confronted with fetal rat brain
      cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel
      for clinical use) in this study showed no effect on tumour cell migration, cell
      proliferation or cell invasion. Scanning confocal microscopy of both cell lines
      showed an extensive random organization of the microtubules in the cytoplasm.
      After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a
      fragmentation of the nuclear material, indicating a possible induction of
      apoptosis. In line with this, flow cytometric DNA histograms showed an
      accumulation of cells in the G2/M phase of the cell cycle after 24 h of
      paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was
      observed indicating nuclear fragmentation.

PMID- 9192977
TI  - Expression of transforming growth factors beta-1, beta 2 and beta 3 in human
      bladder carcinomas.
AB  - We previously detected elevated transforming growth factor beta-1 (TGF-beta1)
      serum levels in patients with invasive bladder carcinomas. In this study, we
      therefore investigated whether elevated serum levels correlate with enhanced TGF
      beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and 
      beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of
      the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were
      found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1))
      and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with
      normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however,
      contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither
      in mean nor in individual patients were serum and tissue TGF-beta levels
      correlated with each other. Cell culture experiments on primary bladder cells
      revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal
      epithelial cells. Tumour epithelial cells contained about two times higher levels
      of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts
      expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells.
      Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour
      epithelial cells into the supernatant. TGF-beta3, on the other hand, was
      expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1
      was the predominent isoform in bladder tissue and cells at protein as well as on
      mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in
      bladder cancer. In summary, there is a lack of correlation between TGF-beta serum
      levels and TGF-beta expression in tumour tissue in bladder cancer.

PMID- 9192979
TI  - Early gastric cancer mimicking advanced gastric cancer.
AB  - The clinicopathological features of 37 early gastric cancers mimicking advanced
      gastric cancer were reviewed retrospectively, and were compared with 596 other
      early gastric cancers and 126 mp gastric cancers, defined as gastric cancer
      invading the muscularis propria of the stomach. A greater tumour size (P <
      0.005), submucosal invasion (P < 0.005), lymph node and lymph vessel invasion (P
      < 0.005) and vascular invasion (P < 0.025) were found more frequently in early
      gastric cancers mimicking advanced gastric cancers than in other early gastric
      cancers. There were no significant differences in the clinicopathological
      findings between early gastric cancers mimicking advanced gastric cancers and mp
      gastric cancers. Patients with early gastric cancers mimicking advanced gastric
      cancers showed a lower survival rate than patients with other early gastric
      cancers, but a higher survival than those with mp gastric cancers. The
      macroscopic appearance of an advanced gastric cancer was an indicator of massive
      submucosal invasion and lymph node metastasis in early gastric cancer. As early
      gastric cancers mimicking advanced gastric cancers showed similar
      clinicopathological findings to mp gastric cancers, these cancers should be
      treated as mp gastric cancers.

PMID- 9192978
TI  - Abnormal expression of CCND1 and RB1 in resection margin epithelia of lung cancer
      patients.
AB  - Tumours develop through the accumulation of genetic alterations associated with a
      progressive increase of the malignant phenotype. In lung cancer, chronic exposure
      of bronchial epithelium to carcinogens in cigarette smoke may lead to multiple
      dysplastic and hyperplastic lesions scattered throughout the tracheobronchial
      tree. Little is known about the genetic alterations in such lesions. This study
      was carried out to examine cyclin D1 (CCND1) and retinoblastoma (RB1) gene
      expression in the bronchial epithelium of patients with lung cancer. Lung tumours
      and their corresponding tumour-free resection margins from 33 patients who
      underwent resection of non-small-cell lung cancer (NSCLC) were examined by
      immunostaining with monoclonal antibodies against cyclin D1 (DCS-6; Novocastra)
      and pRb (NCL Rb-1; Novocastra). Examination of the resection margins revealed
      four carcinomas in situ, 19 hyperplasias and ten sections showing apparently
      normal bronchial epithelium. A control group of patients, without lung tumours
      and who had never smoked, revealed no or weak cyclin D1 and positive pRb staining
      within bronchial epithelia. Increased cyclin D1 and diminished pRb expression
      were found in 76% (n = 25) and 27% (n = 9) of the resection margins respectively,
      and in 12% (n = 4) both cyclin D1 and pRb expression were altered. In the
      corresponding tumours, 48% (n = 16) were normal, while altered expression was
      found for cyclin D1 in 33% (n = 11), pRb in 27% (n = 9) and both in 9% (n = 3) of
      cases. It appears that altered expression of cyclin D1 and pRb is an early event
      in NSCLC development in almost half of cases analysed. Further investigations are
      needed to determine the significance of immunostaining of bronchial specimens in
      individuals at risk of lung cancer, with the possibility that the observations
      are of importance in the early diagnosis of NSCLC.

PMID- 9192981
TI  - Low specificity of PGP9.5 expression for detection of micrometastatic
      neuroblastoma.
AB  - To determine the specificity of neuroendocrine protein gene product (PGP9.5) gene
      transcripts for detecting micrometastatic neuroblastoma, we have used a highly
      sensitive polymerase chain reaction (PCR) technique to evaluate expression of
      this gene in normal blood and bone marrow. While expression of the tyrosine
      hydroxylase gene was not detected in any normal sample, low-level PGP9.5
      expression was detected in eight out of ten blood and seven of 12 marrow samples.
      PGP9.5 gene transcripts in normal tissues have the potential to interfere with
      the detection of micrometastatic neuroblastoma.

PMID- 9192980
TI  - Cyclin A is associated with an unfavourable outcome in patients with non-small
      cell lung carcinomas.
AB  - Specimens of formalin-fixed, paraffin-embedded non-small-cell lung carcinomas
      (NSCLCs; n = 187) were analysed immunohistochemically for expression of cyclin A.
      The analysis was intended to determine whether cyclin A has additional prognostic
      value for predicting patients' survival and drug response. Of the 187 NSCLCs, 141
      cases (75%) showed expression of cyclin A. Patients with cyclin A-positive
      carcinomas had significantly shorter median survival times than patients with
      cyclin A-negative carcinomas (79 vs 129 weeks, P = 0.045). Similar results were
      obtained with more homogeneous groups of patients: patients with only T3 tumours,
      patients with epidermoid carcinomas and patients with lymph node involvement. The
      clinical parameters (age, stage, histology, extent of tumour size, lymph node
      involvement) had no influence on expression of cyclin A. A direct correlation
      between cyclin A and the proportion of S-phase cells (P = 0.08) and an inverse
      relationship between cyclin A and the proportion of G0/G1-phase cells (P = 0.04)
      were found. Furthermore, a significant correlation between the expression of
      cyclin A and the response of NSCLC to doxorubicin in vitro was detected (P =
      0.026).

PMID- 9192982
TI  - Evidence for divergence of DNA copy number changes in serous, mucinous and
      endometrioid ovarian carcinomas.
AB  - Comparative genomic hybridization was applied to detect and map changes in DNA
      copy number in 24 well or moderately differentiated epithelial ovarian carcinomas
      (eight serous, eight mucinous and eight endometrioid carcinomas). Twenty-three of
      the 24 tumours showed changes in DNA copy number in one or several regions
      (median 4, range 1-17). Gains were more frequent than losses (ratio 1.6:1.0). The
      most frequent gains occurred in chromosomes 1q (38%), 2p (29%), 7q (25%), 8q(38%)
      and 17q (38%), and the most common losses were located in chromosomes 8p (21%),
      9p (25%) and 13q (21%). High-level amplifications were detected in seven tumours
      at 1q22-32, 2p15-22, 3qcen-23, 6p21-22 and 8q. In the three histological subtypes
      the copy number karyotypes showed substantial differences. Gains at 1q were
      observed in endometrioid (five cases) and serous tumours (four cases). Increased
      copy number at 10q was seen in endometrioid tumours only (four cases), whereas
      gains at 11q occurred mostly in serous tumours (four cases). In mucinous tumours,
      the most common copy number change was a gain at 17q (six cases). The results
      show that, in epithelial ovarian carcinoma, changes in DNA copy number are a rule
      rather than an exception, chromosomes 1, 2, 7, 8, 9, 13 and 17 being the most
      frequently affected. The diverging pattern of genetic changes seen in epithelial
      ovarian carcinomas with different histological phenotypes suggests that various
      pathways may lead to tumorigenesis and/or progression in these subgroups.

PMID- 9192983
TI  - Overexpression of cyclin D1 correlates with early recurrence in superficial
      bladder cancers.
AB  - Cyclin D1 is a cell cycle regulator essential for G1 phase progression and is
      frequently overexpressed in several human tumour types as a consequence of gene
      amplification or chromosomal rearrangements. We analysed the expression of cyclin
      D1 in 75 patients with transitional cell carcinoma (TCC) to investigate the
      possible relationship between its expression and clinical outcome as well as
      histopathological findings using the immunohistochemical method. We observed
      strong staining (++, > 50% positive cells) for cyclin D1 in 19 cases (25.3%) and
      weak staining (+, 5-50% positive cells) in 19 cases (25.3%). Overexpression of
      cyclin D1 was not associated with tumour invasion. No significant association was
      found between overexpression of cyclin D1 and tumour grade (P > 0.05). We
      assessed the differences of disease-free interval in superficial tumours and
      actuarial survival probability in invasive tumours according to the status of
      cyclin D1 expression. Tumours with (++) staining for cyclin D1 recurred much more
      rapidly than (-) and/or (+) staining tumours (P < 0.01 for - vs ++; P < 0.05 for
      + vs ++). However, overexpression of cyclin D1 was not associated with a
      shortened overall survival of patients with invasive tumours (P < 0.1). These
      results suggest that genetic alteration of cyclin D1 appears to be an early event
      in the tumorigenesis of bladder TCC and is associated with early recurrence in
      superficial tumours.

PMID- 9192984
TI  - Contribution of plasminogen activators and their inhibitors to the survival
      prognosis of patients with Dukes' stage B and C colorectal cancer.
AB  - Despite the advances in pre-, peri- and post-operative medical care of colorectal
      carcinoma patients, the prognosis has improved only marginally over recent
      decades. Thus, additional prognostic indicators would be of great clinical value
      to select patients for adjuvant therapy. In previous studies we found that
      colorectal carcinomas have a marked increase of the urokinase-type of plasminogen
      activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type
      plasminogen activator (t-PA) is found to be decreased in comparison with adjacent
      normal mucosa. In the present study we evaluated the prognostic value of several
      plasminogen activation parameters, determined in both normal and carcinomatous
      tissue from colorectal resection specimens, for overall survival of 136 Dukes'
      stage B and C colorectal cancer patients, in relation to major
      clinicopathological parameters. Uni- and multivariate analyses indicated that a
      high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and
      a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly
      associated with a poor overall survival. A high ratio of u-PA antigen in the
      carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to
      be predictive of a poor overall survival as well. All these parameters were found
      to be prognostically independent of the clinicopathological parameters.
      Multivariate analysis of combinations of these prognostically significant
      plasminogen activation parameters revealed that they are important independent
      prognostic indicators and have in fact a better prognostic value than their
      separate components. Based on these combined parameters, subgroups of patients
      with Dukes' stage B and C colorectal cancer could be identified as having either
      a high or a low risk regarding overall survival. In conclusion, these findings
      emphasize the relevance of the intestinal plasminogen activation system for
      survival prognosis of patients with colorectal cancer and, in the future, might
      constitute a patient selection criterion for adjuvant therapy.

PMID- 9192985
TI  - Soluble and cell-associated transferrin receptor in lung cancer.
AB  - The expression of transferrin receptor (TfR) has been identified in many
      malignant tumours. In lung cancer, lymphoma and breast cancer, it has been shown
      that the expression of TfR correlates with tumour differentiation, probably
      implying some prognostic value. A soluble form of TfR (sTfR) in human serum has
      been shown to be proportional to the number of cellular TfRs. Based on these data
      we examined the utility of measuring sTfR in the serum and bronchoalveolar lavage
      (BAL) fluid of patients with lung cancer (n = 32) and patients with chronic
      obstructive pulmonary disease (n = 22). BAL fluid was centrifuged to separate the
      supernatant from the cellular component. Cells were lysed in a detergent and cell
      associated TfR was measured by enzyme-linked immunosorbent assay (ELISA) and
      expressed as ng 10(-6) cells in this cellular component. There was no difference
      in serum sTfR between the cancer and chronic obstructive pulmonary disease (COPD)
      groups. A higher level of cell-associated TfR was found in BAL of non-small-cell
      lung cancer patients than in COPD patients (P = 0.01). The calculated number of
      TfR molecules per cell in BAL correlated positively with the percentage of
      macrophages in BAL (P < 0.0001), suggesting that cell-associated TfR in BAL
      originates primarily from macrophages in this fluid. No correlation existed
      between BAL cell-associated TfR and tumour size, nodal status, the presence of
      metastases and serum sTfR. BAL cell-associated TfR was negatively correlated with
      BAL supernatant neuron-specific enolase (NSE) (P = 0.01). A combination of BAL
      supernatant NSE and cell-associated TfR detected lung cancer with a sensitivity
      of 91%, a specificity of 59% and positive and negative predictive values of 81%
      and 71% respectively. In conclusion, BAL cell-associated TfR may help in the
      differential diagnosis of lung cancer vs pneumonia.

PMID- 9192986
TI  - Hyaluronidase activity in gynaecological cancer tissues with different metastatic
      forms.
AB  - We investigated hyaluronidase activity in gynaecological normal and malignant
      tissues. Hyaluronidase activity in culture medium of tissue specimens was
      detected by hyaluronic acid zymography and quantified by densitometry.
      Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa)
      at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P <
      0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa
      hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and
      in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase
      activity was not observed in cervical cancer tissues. Hyaluronidase activity was
      significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer
      tissues than in cervical cancer tissue and was significantly higher in ovarian
      cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest
      that the cancer cells make use of the original characteristic of the organ to
      invade and metastasize. Moreover, these results reflect the difference in
      metastatic forms and are suggestive of a strong relationship between
      hyaluronidase activity and invasion and metastasis of ovarian and endometrial
      cancers compared with cervical cancer.

PMID- 9192987
TI  - In vivo and in vitro biotransformation of the lithium salt of gamma-linolenic
      acid by three human carcinomas.
AB  - Lipid metabolism has been considered recently as a novel target for cancer
      therapy. In this field, lithium gamma-linolenate (LiGLA) is a promising
      experimental compound for use in the treatment of human tumours. In vivo and in
      vitro studies allowed us to assess the metabolism of radiolabelled LiGLA by
      tumour tissue and different organs of the host. In vitro studies demonstrated
      that human pancreatic (AsPC-1), prostatic (PC-3) and mammary carcinoma (ZR-75-1)
      cells were capable of elongating GLA from LiGLA to dihomo-gamma-linolenic acid
      (DGLA) and further desaturating it to arachidonic acid (AA). AsPC-1 cells showed
      the lowest delta5-desaturase activity on DGLA. In the in vivo studies, nude mice
      bearing the human carcinomas were given Li[1-(14)C]GLA (2.5 mg kg(-1)) by
      intravenous injection for 30 min. Mice were either sacrificed after infusion or
      left for up to 96 h recovery before sacrifice. In general, the organs showed a
      maximum uptake of radioactivity 30 min after the infusion started (t = 0).
      Thereafter, in major organs the percentage of injected radioactivity per g of
      tissue declined below 1% 96 h after infusion. In kidney, brain, testes/ovaries
      and all three tumour tissues, labelling remained constant throughout the
      experiment. The ratio of radioactivity in liver to tumour tissues ranged between
      16- and 24-fold at t = 0 and between 3.1- and 3.7-fold at 96 h. All tissues
      showed a progressive increase in the proportion of radioactivity associated with
      AA with a concomitant decrease in radiolabelled GLA as the time after infusion
      increased. DGLA declined rapidly in liver and plasma, but at a much slower rate
      in brain and malignant tissue. Seventy-two hours after the infusion, GLA was only
      detected in plasma and tumour tissue. The sum of GLA + DGLA varied among tumour
      tissues, but it remained 2-4 times higher than in liver and plasma. In brain,
      DGLA is the major contributor to the sum of these fatty acids. Data showed that
      cytotoxic GLA and DGLA, the latter provided either by the host or by endogenous
      synthesis, remained in human tumours for at least 4 days.

PMID- 9192989
TI  - High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in
      human breast tumours.
AB  - Despite the presence of a lymphocytic infiltrate in solid cancers, the failure
      for tumour growth to be contained suggests an inadequate immune response to the
      tumour. Poor cytotoxicity exerted by tumour-infiltrating lymphocytes (TILs)
      against tumour cells in vitro, combined with continued tumour growth in vivo,
      suggests deficiencies in TIL function or numbers. Various theories have been
      postulated to explain how tumour cells may escape immunosurveillance and control.
      One of the many hypotheses is the failure of production of cytokines, which are
      necessary for T cells to mediate their function. Thus, the expression of cytokine
      mRNA in human breast tumour sections was investigated by reverse transcriptase
      polymerase chain reaction (RT-PCR) with cytokine-specific primers. A relatively
      consistent finding was detection of interleukin (IL) 10 mRNA among the tumours.
      No IL-2 and little IL-4 mRNA was detected in the tumours. IL-6 and IL-10 mRNA was
      detected in only one and two of the normal breast tissues respectively. IL-2, IL
      4 and tumour necrosis factor (TNF)-alpha mRNA was not detected in any of the
      normal breast tissues. The reduced function of TILs may be related to IL-10,
      which has known inhibitory effects on T-cell activation.

PMID- 9192990
TI  - Involvement of chromosome 6 in endometrial cancer.
AB  - Cytogenetic investigation was performed on direct preparations of 15 endometrial
      cancers showing different histotypes. Clonal abnormalities were found in 11 out
      of 13 analysable cases. The modal chromosome number was near diploid in all
      cases. The abnormal karyotypes contained relatively simple numerical or
      structural aberrations in the majority of tumours. In contrast, two neoplasms
      with serous papillary and mixed mullerian morphological features shared multiple
      complex changes as well as cytogenetic evidence of intratumoral heterogeneity.
      The most frequent chromosome abnormality in our series of endometrial neoplasms
      was 6q deletion, which was detected in serous papillary, endometrioid and mixed
      mullerian tumours. The loss of the 6q region, which is also frequently involved
      in ovarian carcinoma, suggests a relationship between endometrial and ovarian
      cancers based on a common histogenesis.

PMID- 9192988
TI  - Parathyroid hormone-related protein secretion is inhibited by oestradiol and
      stimulated by antioestrogens in KPL-3C human breast cancer cells.
AB  - We recently established a human breast cancer cell line, KPL-3C, from a breast
      cancer patient with humoral hypercalcaemia. This cell line possesses oestrogen
      receptor (ER) and secretes parathyroid hormone-related protein (PTHrP) into
      medium. To investigate the effects of oestrogen and antioestrogens on PTHrP
      secretion, KPL-3C cells were cultured for 48 h in an oestrogen-eliminated medium
      with 17beta-oestradiol (E2), tamoxifen (TAM) and/or a pure antioestrogen,
      ICI182,780 (ICI), and PTHrP secretion was measured using an immunoradiometric
      assay. The effects of these agents on cell cycle progression were also studied
      using flow cytometry. E2 (1-100 nM) significantly inhibited PTHrP secretion,
      whereas both TAM (0.1-10 microM) and ICI (1-100 nM) significantly stimulated it.
      These effects were completely blocked by the simultaneous addition of 1 nM E2 to
      the medium. At the same time, E2 significantly increased the percentage of cells
      during the S and G2/M phases, whereas both antioestrogens significantly increased
      the percentage of cells during the G0/G1 phase. Again, these cytostatic effects
      were completely reversed by the addition of E2. These findings indicate that
      antioestrogens inhibit the growth of ER-positive breast cancer cells but may
      stimulate PTHrP secretion and that these effects may be mediated by ER.

PMID- 9192991
TI  - Treatment of node-positive endometrial cancer with complete node dissection,
      chemotherapy and radiation therapy.
AB  - We assessed the therapeutic significance of systematic aortic and pelvic
      lymphadenectomy followed by adjuvant therapy in node-positive endometrial
      carcinoma. Among 173 stage I-III patients, 30 (17%) had positive nodes: ten in
      the pelvic region alone (group P) and 20 in the aortic region alone or in both
      regions (group A). The adjuvant therapy was administered as follows: subjects in
      group P received 50 Gy pelvic radiation, including three post-surgical T3 (pT3)
      patients who received either one or three cycles of cisplatin-based chemotherapy
      before radiation. Subjects in group A were given three cycles of chemotherapy
      followed by 50 Gy pelvic and 50 Gy extended field periaortic radiation using a
      four-field or conformational technique. Five-year survival was 95% for 143
      patients with negative nodes and 84% for 30 patients with positive nodes (100%
      for group P and 75% for group A). In group A, 5-year survival was 38% for eight
      patients with both pT3 and histology other than endometrioid type G1, and 91% for
      the remaining 12 patients. Either way, both group P and group A patients had a
      better prognosis than previously reported. In summary, aortic and pelvic
      lymphadenectomy and subsequent chemotherapy and radiation therapy based on node
      status seem to improve the survival of endometrial cancer patients with positive
      nodes.

PMID- 9192992
TI  - Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2:
      evidence for non-renal clearance of cytokines.
AB  - The circulating cytokine concentrations following administration of subcutaneous
      recombinant interleukin 2 (IL-2) in combination with interferon alpha and 5
      fluorouracil used to treat advanced renal cancer were studied. One patient was
      anephric and on dialysis, and seven had normal biochemical renal function,
      although five had undergone single nephrectomy. The pharmacokinetics of IL-2 and
      changes in IL-6 and tumour necrosis factor (TNF)-alpha were essentially similar
      in all patients including the anephric patient, irrespective of the periods of
      dialysis, although at some time points, IL-2 concentrations were slightly higher
      in the anephric patient than in the others. These results show that for
      subcutaneous administration of low-dose IL-2, renal clearance of IL-2 is not
      important. This contrasts with high-dose, intravenous IL-2 where blood
      concentrations are higher and renal clearance seems to occur, perhaps because of
      saturation of the non-renal mechanisms of clearance. The subcutaneous route is
      certainly preferred if IL-2 is used in anephric patients and in those with
      impaired renal function, and it may be generally preferred for most purposes.

PMID- 9192994
TI  - Histopathological data.

PMID- 9192993
TI  - Prophylactic intracavitary treatment with interferon alpha increases interferon
      gamma production by peripheral blood mononuclear cells in patients with
      superficial transitional cell carcinoma of the bladder.
AB  - The immunomodulatory effect of prophylactic intravesical instillations of
      interferon alpha 2b (IFN-alpha-2b) on interferon gamma (IFN-gamma) and
      interleukin 4 (IL-4) production by peripheral blood mononuclear cells (PBMCs)
      from patients with superficial transitional cell carcinoma (STCC) of the bladder
      has been analysed. There were no significant differences in the production of IFN
      gamma and IL-4 by PBMCs from untreated patients and healthy control subjects
      after 24 h of phytohaemagglutinin (PHA) stimulation. However, between 3 and 6
      months after finishing the prophylactic intracavitary treatment with IFN-alpha
      2b, PHA-stimulated PBMCs from patients with STCC of the bladder showed a
      significantly enhanced production of IFN-gamma and a significantly decreased
      production of IL-4. Both IFN-gamma and IL-4 returned to pretreatment levels 1
      year after ending the treatment. In conclusion, prophylactic intravesical
      instillations of IFN-alpha-2b in patients with STCC of the bladder have an
      immunoregulatory effect on the production of IFN-gamma and IL-4 by PBMCs.

PMID- 9192995
TI  - BRCA1 polymorphisms.

PMID- 9192996
TI  - Species-specific tRNA recognition in relation to tRNA synthetase contact
      residues.
AB  - In spite of variations in the sequences of tRNAs, the genetic code (anticodon
      trinucleotides) is conserved in evolution. However, non-anticodon nucleotides
      which are species specific are known to prevent a given tRNA from functioning in
      all organisms. Conversely, species-specific tRNA contact residues in synthetases
      should also prevent cross-species acylation in a predictable way. To address this
      question, we investigated the relatively small tyrosine tRNA synthetase where
      contacts of Escherichia coli tRNA(Tyr) with the alpha2 dimeric protein have been
      localized by others to four specific sequence clusters on the three-dimensional
      structure of the Bacillus stearothermophilus enzyme. We used specific functional
      tests with a previously not-sequenced and not-characterized Mycobacterium
      tuberculosis enzyme and showed that it demonstrates species-specific
      aminoacylation in vivo and in vitro. The specificity observed fits exactly with
      the presence of the clusters characteristic of those established as important for
      recognition of E. coli tRNA. Conversely, we noted that a recent analysis of the
      tyrosine enzyme from the eukaryote pathogen Pneumocystis carinii showed just the
      opposite species specificity of tRNA recognition. According to our alignments,
      the sequences of the clusters diverge substantially from those seen with the M.
      tuberculosis, B. stearothermophilus and other enzymes. Thus, the presence or
      absence of species-specific residues in tRNA synthetases correlates in both
      directions with cross-species aminoacylation phenotypes, without reference to the
      associated tRNA sequences. We suggest that this kind of analysis can identify
      those synthetase-tRNA covariations which are needed to preserve the genetic code.
      These co-variations might be exploited to develop novel antibiotics against
      pathogens such as M. tuberculosis and P. carinii.

PMID- 9192997
TI  - Mechanism of inhibition of bacteriophage T7 RNA polymerase by T7 lysozyme.
AB  - Bacteriophage T7 lysozyme is known to inhibit transcription by T7 RNA polymerase.
      Lysozyme present before initiation inhibited the synthesis of long RNA chains but
      did not inhibit elongation when added shortly after chains were initiated. A
      combination of gel-shift and transcription assays showed that lysozyme and
      polymerase form a 1:1 complex that binds promoter DNA and makes abortive
      transcripts, indicating that lysozyme has little effect on the early steps of
      transcription. Extension of stalled transcription complexes suggested that a
      transcribing polymerase becomes resistant to lysozyme inhibition after synthesis
      of an RNA chain as short as 15 nucleotides. It seems likely that bound lysozyme
      prevents an initiating polymerase from converting to an elongation complex. This
      conversion is thought to involve both a conformational change in the polymerase
      and the binding of nascent RNA. Gel-shift experiments indicated that lysozyme
      does not interfere with the binding of RNA, so it probably prevents a necessary
      conformational change in the polymerase. Lysozyme also increased pausing or
      termination at two sites in lambda DNA and at a site near the right end of the
      concatemer junction of T7 DNA. If pausing at these sites involves a reversal from
      the elongation to the initiation conformation, lysozyme may increase pausing or
      termination by "locking in" the initiation conformation. The arrest of
      transcription complexes near promoters and near the right end of the concatemer
      junction almost certainly must relate to lysozyme's ability to stimulate
      replication, maturation and packaging of T7 DNA during T7 infection.

PMID- 9192998
TI  - Mutant bacteriophage T7 RNA polymerases with altered termination properties.
AB  - We have identified mutants of bacteriophage T7 RNA polymerase (RNAP) that are
      altered in their ability to pause or terminate at a variety of signals. These
      signals include a terminator found fortuitously in the human preproparathyroid
      hormone (PTH) gene, a pause site found in the concatamer junction (CJ) of
      replicating T7 DNA, and termination signals that are also utilized by Escherichia
      coli RNAP (e.g. rrnB T1 and T2). Whereas the mutant enzymes terminate normally at
      the late terminator in T7 DNA (T(phi)) and rrnB T2, they fail to terminate at one
      of the termination sites of rrnB T1, and also fail to recognize the PTH and CJ
      signals. The mutant enzymes exhibit normal processivity on linear templates, but
      show a slightly reduced processivity on supercoiled templates and terminate more
      efficiently when synthesizing poly(U) tracts. The mutant enzymes also show a
      decreased tendency to produce aberrant transcription products from DNA templates
      having protruding 3' ends. T7 lysozyme (an inhibitor of T7 RNAP) has been shown
      to exert its action by preventing the transition of the RNAP from an unstable
      initiation complex (IC) to a stable elongation complex (EC). We have found that
      T7 lysozyme enhances recognition of CJ by wild-type T7 RNAP, and that mutant T7
      RNAPs that show increased sensitivity to lysozyme show enhanced recognition of
      this signal, even in the absence of lysozyme. These results, together with the
      observation that the mutations that result in the termination-deficient phenotype
      affect a region of the RNAP that has been implicated in RNA binding and upstream
      promoter contacts, support the hypothesis that, in some cases, termination
      represents a reversal of the events that occur during initiation.

PMID- 9192999
TI  - The low processivity of T7 RNA polymerase over the initially transcribed sequence
      can limit productive initiation in vivo.
AB  - In vitro, after binding to the promoter to form a catalytically active complex,
      RNA polymerases abortively cycle over the first transcribed nucleotides (initial
      transcribed sequence or ITS) before leaving the promoter. With the bacteriophage
      T7 enzyme, the extent of abortive transcription varies with the nature of the ITS
      and with the elongation speed of the polymerase. Here, we compare in vitro and in
      vivo the yield of long transcripts from T7 promoters, with two different ITSs,
      the T7 gene10 and the lactose operon ITSs, and two different T7 RNA polymerases,
      the wild-type and a 2.7-fold slower mutant (G645A). The use of non-cognate ITS
      and/or slow polymerase decreases the yield of long transcripts in vitro and in
      vivo in a parallel fashion, with low polymerase speed and non-cognate ITS acting
      synergistically. In vitro, this decrease is mirrored by an increase in the
      average number of abortive cycles the enzyme undergoes before leaving the
      promoter; specifically, with the G645A mutant, transcript release is favored at
      any ITS position, whereas with the lac ITS it is particularly frequent at
      positions five and six following the incorporation of uridine residues. Hence,
      the more abortive cycles per long transcript synthesis in vitro, the lower the
      yield of long transcripts in vitro or in vivo. We conclude that the duration of
      abortive cycling can limit long transcript synthesis in vivo, as in vitro. Under
      conditions where cycling is minimal (wild-type polymerase, gene10 ITS), T7
      promoter drives the synthesis of three long transcripts per second at 37 degrees
      C in vivo, a figure higher than for any Escherichia coli promoter.

PMID- 9193001
TI  - Differential effects of aromatic and charged residue substitutions in the RNA
      binding domains of the yeast poly(A)-binding protein.
AB  - The yeast poly(A)-binding protein (Pab1p) contains four RNA recognition motifs
      (RRMs). Site-directed mutations were introduced into each of these RRMs in order
      to investigate their relative contributions to specific and non-specific RNA
      binding, and to determine the consequences of these mutations on the ability of
      Pab1p to support viability. Specifically, a charged and an aromatic residue that
      were predicted to be involved in RNA binding were mutated in each RRM. These
      mutations revealed that the second RRM is primarily responsible for poly(A)
      binding, while the fourth RRM is primarily responsible for non-specific
      polypyrimidine RNA binding. The mutated aromatic residues in each RRM contributed
      to both modes of binding whereas the mutated charged residues contributed
      primarily to non-specific RNA binding. RNA binding in vivo correlated with the in
      vitro binding measurements. Furthermore, RNA binding, but not high-affinity
      poly(A) binding, correlated with the ability of Pab1p to sustain yeast cell
      viability. These data suggest that a single aromatic substitution in Pab1p can
      significantly reduce its RNA binding ability, that the capacity of Pab1p to bind
      poly(A) as well as other RNAs is mediated by distinct residues within different
      RRMs, and that Pab1p does not require high affinity poly(A) tail binding to
      perform its essential function.

PMID- 9193000
TI  - The structure of an RNA "kissing" hairpin complex of the HIV TAR hairpin loop and
      its complement.
AB  - We have used nuclear magnetic resonance (NMR) to obtain the structure of an RNA
      "kissing" hairpin complex formed between the HIV-2 TAR hairpin loop and a hairpin
      with a complementary loop sequence. Kissing hairpins are important in natural
      antisense reactions; their complex is a specific target for protein binding. The
      complex has all six nucleotides of each loop paired to form a bent
      quasicontinuous helix of three coaxially stacked helices: two stems plus a loop
      loop interaction helix. Experimental constraints derived from heteronuclear and
      homonuclear NMR data on 13C and 15N-labeled RNA led to a structure for the loop
      loop helix with an average root-mean-square deviation of 0.83 (+/-0.10) A for 33
      converged structures relative to the average structure. The loop-loop helix of
      the kissing complex is distorted compared to A-form RNA. Its major groove is
      blocked by the phosphodiester bonds that connect the first loop residue of each
      hairpin with its own stem, and it is flanked by two negatively charged phosphate
      clusters. The loop-loop helix has alternating helical twists between adjacent
      base-pairs. The base-pairs at the helix junctions are overwound and three base
      pairs near the helix junctions adopt high propeller twists. All these changes
      reduce the distance needed for the bridging phosphodiester bonds connecting each
      stem and loop to cross the major groove of the loop-loop helix, and result in a
      deformed RNA helix with localized perturbations in the minor groove surface. The
      alternating helical twist pattern, plus other distortions in the loop-loop helix
      may be important for Rom protein recognition of the kissing hairpin complex.

PMID- 9193002
TI  - Specific binding by EcoRV endonuclease to its DNA recognition site GATATC.
AB  - Restriction endonuclease EcoRV has been reported to be unable to distinguish its
      specific DNA site, GATATC, from non-specific DNA sites in the absence of the
      catalytic cofactor Mg2+, and thus to exercise sequence specificity solely in the
      catalytic step. In contrast, we show here that under appropriate conditions of pH
      and salt concentration, specific complexes with oligonucleotides containing the
      GATATC site can be detected by either filter-binding or gel-retardation.
      Equilibrium binding constants (K(A)) are easily measured by both direct
      equilibrium and equilibrium-competition methods. The preference for "specific"
      over "non-specific" binding at pH 7 in the absence of divalent cations is about
      1000-fold (per mole of oligonucleotide) or 12,000-fold (per mole of binding
      sites). Ethylation-interference footprinting shows that the "specific" complex
      includes strong contacts to the phosphate groups GpApTpApTC. Specific DNA binding
      is strongly pH-dependent, decreasing about 15-fold for each increase of one pH
      unit above pH 6, but non-specific binding is not; thus, binding specificity
      decreases with increasing pH. Gel retardation and filter-binding at pH < or = 7
      yield essentially identical values of K(A) for specific-site binding, but at pH >
      7 gel retardation significantly underestimates K(A). Specific-site binding is
      stimulated about 700-fold by Ca2+ (not a cofactor for cleavage), but with non
      cleavable 3'-phosphorothiolate and 4'-thiodeoxyribose derivatives whose response
      to Ca2+ is similar to that of the parent oligonucleotide, Mg2+ stimulates binding
      only fourfold and twofold, respectively. Thus, binding specificity is not
      dramatically enhanced by Mg2+. Taking into account discrimination in binding and
      in the first-order rate constant for phosphodiester bond scission, the overall
      discrimination exercised against the incorrect site GTTATC is about 10(7)-fold.
      EcoRV endonuclease is thus not a "new paradigm" for site-specific interaction
      without binding specificity, but like other type II restriction endonucleases
      achieves sequence specificity by discriminating both in DNA binding and in
      catalysis.

PMID- 9193003
TI  - Initiation of bacteriophage phi29 DNA replication in vivo: assembly of a membrane
      associated multiprotein complex.
AB  - Initiation of in vitro phage phi29 DNA replication requires the formation of a
      heterodimer between a free molecule of terminal protein (TP), which acts as
      primer, and the viral DNA polymerase. We have analyzed membrane vesicles from
      phi29-infected Bacillus subtilis cells by quantitative immunoblot techniques.
      During phage DNA synthesis, large amounts of the viral proteins p1 and free TP
      were recovered in membrane fractions, as well as a low percentage of the total
      viral DNA polymerase. Interestingly, the amount of DNA polymerase in membrane
      fractions increased when viral DNA replication was blocked. Both protein p1 and
      free TP showed affinity for membranes in the absence of viral DNA. The
      association of protein p1 with membranes was abolished when the C-terminal 43
      amino acid residues were deleted. The above results, together with the critical
      role of protein p1 for in vivo phi29 DNA replication, led us to conclude that a
      preliminary stage in the initiation of in vivo phi29 DNA replication could be the
      assembly of a membrane-associated multiprotein complex containing at least
      protein p1, free TP and DNA polymerase. Membrane-attachment of this complex could
      be directly mediated by both protein p1 and free TP. The ability of free TP to
      bind to membranes and to prime phi29 DNA replication would enable a nascent viral
      DNA molecule to become membrane-associated when its synthesis begins. We
      postulate that a general function of the TPs covalently linked to linear DNA
      genomes in prokaryotes might be, in addition to act as primer, to anchor the
      linear DNA molecule to the bacterial membrane.

PMID- 9193004
TI  - Electrostatics and hydration at the homeodomain-DNA interface: chemical probes of
      an interfacial water cavity.
AB  - Electrostatics and hydration of a homeodomain-DNA complex are dissected by
      chemical modification. Selective neutralization of phosphate charges by
      methylphosphonate substitution demonstrates the differential importance of short-
      and long-range electrostatic interactions. Whereas the footprint of direct
      contacts is in accord with crystal structures, interference is also observed at
      non-contacted sites. Such sites adjoin a novel interfacial water cavity in the
      major groove. Non-contacted phosphodiester groups in the cavity are proposed to
      contribute to long-range ordering of an extended protein-water-DNA interface. Use
      of isolated S(p) and R(p) methylphosphonate diastereomers demonstrates that
      interference at this extended interface is stereoselective and charge
      independent. Attenuation of protein binding presumably reflects groove-specific
      reorganization of bound water. Surprisingly, such attenuation can exceed that due
      to neutralization of a direct phosphate-side-chain salt bridge. These results
      support the hypothesis that hydration of an interfacial cavity functions as a non
      covalent extension of the DNA surface. Stereo-specific interrogation of bound
      water by chemical synthesis provides a general method to assess the coupling
      between solvation and DNA recognition.

PMID- 9193005
TI  - Molecular structure of the lipoamide dehydrogenase domain of a surface antigen
      from Neisseria meningitidis.
AB  - The protein p64k from the surface of the Neisseria meningitidis bacteria has been
      characterized as a two-domain protein. It contains a dihydrolipoamide
      dehydrogenase domain of 482 residues, involving a FAD prosthetic group as a
      cofactor, and a smaller lipoic acid binding domain of 86 residues. The two
      domains are joined by a flexible segment rich in alanine and proline residues.
      The structure of the dihydrolipoamide dehydrogenase domain was determined by X
      ray diffraction. It was solved by a combination of molecular replacement and
      multiple isomorphous replacement techniques and refined to 2.7 A resolution. In
      the crystal, the recombinant p64k mimics the functional homo-dimer by using one
      of the crystallographic 2-fold axes. The reactive disulphide bridge Cys161-Cys166
      is in the oxidised state and the FAD is bound in an extended conformation. This
      main domain contains the major antigenic determinant of the protein, an extended
      loop of 32 residues at the surface of the protein. A mis-attribution at residue
      553 in the sequence has been detected by inspection of electron density maps and
      the geometry. However, when compared to the other dihydrolipoamide
      dehydrogenases, there are some significant differences: (1) an unusual number of
      cis-proline residues and (2) a new motif built around a 2-fold axis by the
      sulphur atoms of residues Met558, Cys560 and their symmetry related equivalents.

PMID- 9193006
TI  - The refined crystal structure of Bacillus cereus oligo-1,6-glucosidase at 2.0 A
      resolution: structural characterization of proline-substitution sites for protein
      thermostabilization.
AB  - The crystal structure of oligo-1,6-glucosidase (dextrin 6-alpha-glucanohydrolase,
      EC 3.2.1.10) from Bacillus cereus ATCC7064 has been refined to 2.0 A resolution
      with an R-factor of 19.6% for 43,328 reflections. The final model contains 4646
      protein atoms and 221 ordered water molecules with respective root-mean-square
      deviations of 0.015 A for bond lengths and of 3.166 degrees for bond angles from
      the ideal values. The structure consists of three domains: the N-terminal domain
      (residues 1 to 104 and 175 to 480), the subdomain (residues 105 to 174) and the C
      terminal domain (residues 481 to 558). The N-terminal domain takes a
      (beta/alpha)8-barrel structure with additions of an alpha-helix (N alpha6')
      between the sixth strand Nbeta6 and the sixth helix N alpha6, an alpha-helix (N
      alpha7') between the seventh strand Nbeta7 and the seventh helix N alpha7 and
      three alpha-helices (N alpha8', N alpha8" and N alpha8'" between the eighth
      strand Nbeta8 and the eighth helix N alpha8. The subdomain is composed of an
      alpha-helix, a three-stranded antiparallel beta-sheet, and long intervening
      loops. The C-terminal domain has a beta-barrel structure of eight antiparallel
      beta-strands folded in double Greek key motifs, which is distorted in the sixth
      strand Cbeta6. Three catalytic residues, Asp199, Glu255 and Asp329, are located
      at the bottom of a deep cleft formed by the subdomain and a cluster of the two
      additional alpha-helices N alpha8' and N alpha8" in the (beta/alpha)8-barrel. The
      refined structure reveals the locations of 21 proline-substitution sites that are
      expected to be critical to protein thermostabilization from a sequence comparison
      among three Bacillus oligo-1,6-glucosidases with different thermostability. These
      sites lie in loops, beta-turns and alpha-helices, in order of frequency, except
      for Cys515 in the fourth beta-strand Cbeta4 of the C-terminal domain. The
      residues in beta-turns (Lys121, Glu208, Pro257, Glu290, Pro443, Lys457 and
      Glu487) are all found at their second positions, and those in alpha-helices
      (Asn109, Glu175, Thr261 and Ile403) are present at their N1 positions of the
      first helical turns. Those residues in both secondary structures adopt phi and
      phi values favorable for proline substitution. Residues preceding the 21 sites
      are mostly conserved upon proline occurrence at these 21 sites in more
      thermostable Bacillus oligo-1,6-glucosidases. These structural features with
      respect to the 21 sites indicate that the sites in beta-turns and alpha-helices
      have more essential prerequisites for proline substitution to thermostabilize the
      protein than those in loops. This well supports the previous finding that the
      replacement at the appropriate positions in beta-turns or alpha-helices is the
      most effective for protein thermostabilization by proline substitution.

PMID- 9193007
TI  - Enhanced protein flexibility caused by a destabilizing amino acid replacement in
      BPTI.
AB  - A genetically engineered variant of bovine pancreatic trypsin inhibitor (Y35G
      BPTI) has been shown previously by X-ray crystallography to have a three
      dimensional structure dramatically different from that of the wild-type protein,
      particularly in the protease-binding region of the molecule. Yet, the Y35G
      variant is a potent trypsin inhibitor. Described here are 15N NMR relaxation
      studies to compare the backbone dynamics of Y35G BPTI to those of the wild-type
      protein. The Tyr35 --> Gly substitution increased the transverse relaxation rates
      of more than one third of all backbone amide groups, but had little effect on the
      longitudinal relaxation rates, indicating that the substitution facilitates
      relatively slow backbone motions, estimated to be on the microsecond time-scale.
      The results indicate that the residues making up the trypsin-binding site undergo
      large and relatively slow conformational changes in solution, estimated to be on
      the 5 to 20 micros time-scale. It is thus likely that the crystal structure
      represents only one of multiple interconverting conformations in solution, only a
      fraction of which may be competent for binding trypsin. The large thermodynamic
      destabilization associated with this substitution may arise, in part, from a loss
      in cooperativity among the multiple stabilizing interactions that are normally
      favored by the highly ordered structure of the wild-type protein. These results
      suggest that fully understanding the effects of amino acid replacements on the
      functional and thermodynamic properties of proteins may often require analysis of
      the dynamic, as well as the structural, properties of altered proteins.

PMID- 9193008
TI  - Interaction between enalapril and aspirin on mortality after acute myocardial
      infarction: subgroup analysis of the Cooperative New Scandinavian Enalapril
      Survival Study II (CONSENSUS II)
AB  - The use of angiotensin-converting enzyme (ACE) inhibitors early after an acute
      myocardial infarction to reduce mortality has been studied in several trials with
      inconsistent results. Aspirin (ASA) has become a well-documented therapeutic
      adjunct in patients with coronary heart disease. Attention has recently been
      focused on a possible interaction between ASA and ACE inhibitors. We therefore
      reanalyzed data from the Cooperative New Scandinavian Enalapril Survival Study II
      (CONSENSUS II) to find any evidence of differential effects of the ACE inhibitor
      enalapril in subgroups defined by use of ASA at baseline. Logistic regression
      tested the multiplicative interaction. We used Rothman synergy index S, which
      would be equal to unity under additivity, and less than unity when suggesting
      antagonism, to examine the postulated interaction with departure from an additive
      model. Logistic regression showed that the enalapril-ASA interaction term was a
      significant predictor of mortality at the end of the study (p = 0.047), and was a
      borderline significant predictor of mortality 30 days after randomization (p =
      0.085). The Rothman synergy index S was 0.66 (95% confidence interval 0.46 to
      0.94) for mortality at the end of the study, and 0.68 ( 0.44 to 1.04) for 30-day
      mortality, indicating antagonism between enalapril and ASA with departure from an
      additive model. Thus, we found evidence of enalapril-ASA interaction. The effect
      of enalapril was less favorable among patients taking ASA than among patients not
      taking ASA at baseline.

PMID- 9193009
TI  - Serum iron level, coronary artery disease, and all-cause mortality in older men
      and women.
AB  - The association between iron levels and coronary artery disease (CAD) mortality
      is controversial. Whereas most data show no association, some have raised the
      possibility of a causal role, while others have suggested a protective effect of
      iron on CAD. To address these possibilities, we examined the association between
      serum iron and CAD, cardiovascular disease, and all-cause mortality in a large
      cohort of 3,936 persons aged > or =71 years who completed an interview, had a
      serum iron determination, and survived at least 1 year after baseline. The median
      follow-up time was 4.4 years. Serum iron levels were categorized according to sex
      specific quartiles. Relative risks (RR) and 95% confidence intervals (CI) were
      calculated from proportional-hazards regression models adjusted for age, race,
      education, creatinine, serum albumin, serum lipids, use of iron supplementation,
      smoking, use of alcohol, blood pressure, body mass index, and presence of chronic
      conditions. There was a gradual decrease in the RRs of CAD, cardiovascular
      disease, and all-cause mortality with increasing serum iron levels (all tests for
      trend, p <0.05). Men in the highest iron quartile were one fifth as likely to die
      of CAD as men in the lowest iron quartile (RR 0.22; 95% CI 0.11 to 0.48), and
      women in the highest quartile had half the risk of women in the lowest quartile
      (RR 0.48; 95% CI 0.27 to 0.87). When compared with the lowest quartile, risk of
      all-cause mortality was 38% lower in men in the highest iron quartile (RR 0.62;
      95% CI 0.46 to 0.85) and 28% lower in women in the highest quartile (RR 0.72; 95%
      CI 0.53 to 0.96). Results of similar strength and magnitude were observed for
      cardiovascular disease mortality and in analyses that excluded the first 3 years
      of follow-up. In this large cohort of persons aged > or =71 years, there was
      consistent evidence of increasing risk of mortality at lower serum iron levels.
      In fact, lower serum iron levels were associated with an increased risk of CAD,
      cardiovascular disease, and all-cause mortality. The results are compatible with
      the possibility that in an older population, there is an inverse association
      between serum iron levels and risk of mortality.

PMID- 9193010
TI  - Relation of coronary calcium score by electron beam computed tomography to
      arteriographic findings in asymptomatic and symptomatic adults.
AB  - Coronary arteriography was performed on 18 asymptomatic, apparently healthy
      adults with elevated coronary calcium scores. To extend the range of observation
      to subjects with low calcium scores, arteriograms from 18 patients with
      exertional dyspnea and/or valvular heart disease and low calcium scores were also
      analyzed; these 18 patients were considered asymptomatic from the point of view
      of coronary artery disease (CAD). For the comparison of symptomatic and
      asymptomatic persons, 3 age and sex-matched symptomatic patients were also
      selected for each of the original 18 asymptomatic subjects. Arteriograms were
      analyzed by computer-assisted quantitative coronary arteriography at a remote
      site without knowledge of the calcium score or any other patient characteristics.
      In the 18 asymptomatic subjects with elevated calcium scores, the mean calcium
      score was 573 +/- 504 (Agatston method) and the mean worst stenosis was 45% +/-
      16%. For all 36 patients without symptoms of CAD, worst stenosis was closely
      correlated with the square root of the calcium score (r = 0.85, p <0.0001).
      Patients with symptomatic coronary disease and calcium scores < 1,000 had
      stenoses more severe than asymptomatic persons with similar calcium scores. Most
      asymptomatic adults with elevated calcium scores have nontrivial, nonobstructive
      CAD or preclinical obstructive CAD, and the relation between coronary calcium
      score and severity of stenosis is highly significant. These data indicate that
      electron beam tomography can be used to estimate the severity of CAD in
      asymptomatic persons.

PMID- 9193012
TI  - Euphenic prevention of coronary artery disease.
AB  - The purpose of this feasibility study was to incorporate the primary prevention
      of coronary artery disease (CAD) into periconception care. The first task was the
      preconceptional screening for CAD. The family and case histories and risk status
      of prospective mothers and fathers were obtained. Serum total cholesterol was
      measured in 3,530 female and 3,127 male participants. The mean serum nonfasting
      cholesterol was 192 +/- 40 mg/dl in women and 204 +/- 49 mg/dl in men. The levels
      of total cholesterol exceeded the upper limit of desirable total cholesterol (200
      mg/dl) in 37% of women and in 49% of men. Only 7% of women and 5% of men had
      previous knowledge about their high total cholesterol. The second task was risk
      assessment for CAD in prospective parents and their planned baby and the
      identification of couples at high risk. The third step was the education of
      couples at high risk: how to reduce risk factors and how to enhance protective
      factors. Three months later, the short-term follow-up study indicated a 49 mg/dl
      (18%) and 43 mg/dl (16%) (range 250 to 300) reduction in total cholesterol in
      female and male participants, respectively, mainly due to an education program
      including change in diet, cessation of smoking, and so forth. The long-term
      follow-up will include both parents and children 3 years after the birth.
      Periconception care is appropriate for both a general and selective approach to
      population screening for total cholesterol and for primary prevention of CAD.

PMID- 9193011
TI  - Prevalence of unrecognized silent myocardial ischemia and its association with
      atherosclerotic risk factors in noninsulin-dependent diabetes mellitus. Milan
      Study on Atherosclerosis and Diabetes (MiSAD) Group.
AB  - To determine the prevalence of unrecognized silent myocardial ischemia, 925
      noninsulin-dependent diabetic outpatients (333 women and 592 men), aged 40 to 65
      years, asymptomatic, free from known coronary artery disease (CAD), advanced
      diabetic retinopathy, and nephropathy, severe hypertension, and poor prognosis
      disease, underwent exercise electrocardiogram (ECG), followed, if abnormal, by an
      exercise thallium scintigraphy. The exercise ECG tests were abnormal in 112
      patients (12.1%, 31 women, 81 men), of whom 59 (6.4%, 12 women, 47 men) had
      perfusion defects at thallium scintigraphy. Adopting the more restrictive
      criteria (positive response to both tests) the prevalence of silent CAD resulted
      in 6.4%. Multivariate analysis showed that in the whole population and in the
      men, the associated independent risk factors were age, total cholesterol,
      proteinuria, and ST-T abnormalities at ECG at rest. This last factor had the
      highest odds ratio (9.27, confidence interval [CI] 4.44 to 19.38) and was the
      only one identified also in women. The relevance of ST-T abnormalities at ECG at
      rest as a predicting factor for silent CAD outlines the importance of a
      periodical ECG at rest in noninsulin-dependent diabetic patients and suggests an
      indication of performance of further investigations in presence of these
      abnormalities.

PMID- 9193013
TI  - Frequency of disabling symptoms in supraventricular tachycardia.
AB  - The purposes of this study were to describe: clinical symptoms in a sample of
      consecutive patients with supraventricular tachycardia (SVT); incidence of sudden
      death, syncope, and other disabling symptoms; whether these symptoms differ by
      tachycardia mechanism; and to identify predictor variables of syncope in patients
      with SVT. Data were collected from chart reviews of 167 consecutive patients with
      SVT admitted for radiofrequency ablation. Three patients (2%) had nonlethal
      cardiac arrest, and a total of 16% (26 of 183) received at least 1 external
      direct-current shock for arrhythmia management. Twenty percent of subjects (33 of
      167) reported at least 1 episode of syncope which was preceded by palpitations.
      The most frequent symptoms were: palpitations (96%), dizziness (75%), and
      shortness of breath (47%). We found atrioventricular nodal reentrant tachycardia
      (AVNRT) in 64 patients, atrioventricular-reciprocating tachycardia (AVRT) in 59,
      atrial tachycardia in 22, and atrial flutter in 22. The symptom profiles of
      patients with AVNRT, AVRT, and atrial tachycardia were very similar, but differed
      significantly (p <0.05) from those reported in the atrial flutter group.
      Multivariate analysis showed that heart rate > or = 170 beats/min was the only
      independent risk factor for syncope. Chi-square analysis demonstrated that SVT
      patients with heart rate > or = 170 beats/min had significantly more dizziness
      and syncope. Thus, despite a low incidence of associated heart disease, and good
      left ventricular function, there was a high frequency of disabling, potentially
      life-threatening symptoms associated with episodes of SVT in this sample. SVT can
      have potentially lethal consequences, and is more disruptive than previously
      thought.

PMID- 9193014
TI  - Clinical predictors of transvenous defibrillation energy requirements.
AB  - Nonthoracotomy and, more recently, transvenous lead systems have become routine
      for initial implantable cardioverter-defibrillator (ICD) placement. Previous
      studies of clinical predictors of nonthoracotomy defibrillation energy
      requirements evaluated multiple complex lead systems that included subcutaneous
      patches. However, the predictors of an adequate transvenous defibrillation
      threshold (DFT) have not been assessed previously. Accordingly, the present study
      is a prospective evaluation of DFT using a uniform testing protocol in 119
      consecutive patients undergoing ICD implantation with a single transvenous lead.
      For each patient, 38 parameters were assessed including standard clinical,
      echocardiographic, and radiographic measures. An adequate monophasic DFT (< or
      =20 J) was achieved in 76% of patients. Multivariable analysis revealed 3
      independent factors predictive of a high threshold: preoperative amiodarone use
      (odds ratio = 5.8, p < or =0.002), echocardiographic measures of left ventricular
      dilation (odds ratio = 0.47, p < or =0.005) and body size (odds ratio = 0.51, p <
      or =0.006). Patients receiving amiodarone who also had left ventricular dilation
      constitute a group at considerable (69%) risk for having a high DFT. In contrast,
      patients with neither of these risk factors have only an 11% chance of having a
      high threshold. We conclude that an adequate transvenous DFT can be predicted
      from simple clinical parameters.

PMID- 9193016
TI  - Reproducibility of time-domain indexes of heart rate variability in patients with
      vasovagal syncope.
AB  - The aim of this study was to examine whether the indexes of heart rate
      variability (HRV) are stable from day-to-day in patients with vasovagal syncope
      and whether the stability of the HRV indexes is linked with that of the clinical
      results of the tilt test. Nineteen patients with a history of syncopal episodes
      and a positive tilt test underwent a second test 1 week later. Of these, 11
      (group P-P) also had a positive second test, whereas 8 (group P-N) had a negative
      second test. Fifteen healthy volunteers served as a control group. Five time
      domain indexes were derived: the mean of all coupling intervals between normal
      beats (mean NN), the SD about the mean of all coupling intervals between normal
      beats (SDNN), the mean of all 5-minute standard deviations of NNs (SD), the
      proportion of adjacent normal RR intervals differing by >50 ms (pNN50), the root
      mean-square of the difference between successive RRs (rMSSD) and the standard
      deviations of 5-minute mean NN intervals (SDANN). The control group showed good
      reproducibility of all HRV indexes (slope 0.86 to 0.97). The syncopal patients
      taken as a whole had significantly less reproducibility than the controls in the
      pNN50 parameter. This difference was due entirely to the patients in the P-N
      group, who had a remarkable lack of reproducibility in both the pNN50 and rMSSD
      measures (slope pNN50, 0.52; rMSSD, 0.78), whereas the P-P group had a
      reproducibility of all HRV indexes, which was no different from that in controls
      (slope 0.83 to 1.04). In patients with vasovagal syncope, certain HRV measures
      that express parasympathetic tone did not show the high reproducibility found in
      normal subjects. Syncopal patients who lack reproducibility in these HRV
      parameters also show a lack of reproducibility in the clinical result of tilt
      testing.

PMID- 9193015
TI  - The signal-averaged electrocardiogram is of limited value in patients with bundle
      branch block and dilated cardiomyopathy in predicting inducible ventricular
      tachycardia or death.
AB  - An abnormal signal-averaged electrocardiogram (SAECG) has predictive value for
      arrhythmic events in patients with idiopathic dilated cardiomyopathy and a normal
      conduction. The purpose of this study was to investigate whether the presence of
      a complete bundle branch block (BBB) affects prognostic information of the SAECG.
      We prospectively obtained SAECGs in 128 patients with idiopathic dilated
      cardiomyopathy. Forty-three of them had BBB and 85 had a normal QRS duration.
      According to their clinical history and results of ventricular programmed
      stimulation, patients were divided into 4 groups: (1) group IA with BBB and
      ventricular tachycardia (VT) (n = 18); (2) group IB with BBB but without VT (n =
      25); (3) group IIA without BBB but with VT (n = 40); (4) group IIB without BBB
      and without VT (n = 45). Patients were compared with 129 patients without heart
      disease and without VT. Fifty-seven of them had BBB (group III) and 72 had normal
      conduction (group IV). The filtered QRS duration was longer in group IB than in
      group III (175 +/- 21 vs 149 +/- 16 ms, p <0.001), and in group IIB than in group
      IV (111 +/- 19 vs 96 +/- 12 ms, p <0.05). QRS duration was similar in groups IA
      and IB (176 +/- 24 vs 175 +/- 21 ms) but longer in group IIA than in group IIB
      (131 +/- 24 vs 111 +/- 19 ms, p <0.001). The low-amplitude signal duration (LAS)
      and the root-mean-square voltage (RMS) of the last 40 ms of the filtered QRS did
      not differ between groups IB and III and IA and IB. LAS and RMS were,
      respectively, longer (44 +/- 20 vs 31 +/- 13 ms, p <0.01) and lower (21 +/- 20 vs
      43 +/- 33 microV, p <0.001) in groups IIA and IIB. In groups IA and IB the
      combination of 2 of the 3 available criteria: QRS duration >170 ms, RMS <20
      microV, LAS >45 ms lead up to the best overall statistical result, with a
      sensitivity and specificity of 78% and 56%, respectively. In groups IIA and IIB,
      using conventional late potential criteria, the sensitivity and specificity of
      the SAECG for VT detection were 65% and 73%, respectively. The risk of sudden
      death was not predicted by the SAECG, and total cardiac mortality was only
      dependent on left ventricular ejection fraction. In conclusion, QRS duration was
      prolonged in all of the patients with a dilated cardiomyopathy compared with
      those without heart disease. BBB did not change the sensitivity but decreased the
      specificity of the SAECG to predict any VT risk in dilated cardiomyopathy. The
      risk of sudden death and total cardiac mortality could not be predicted by the
      SAECG.

PMID- 9193017
TI  - Comparison of age, gender, number of aortic valve cusps, concomitant coronary
      artery bypass grafting, and magnitude of left ventricular-systemic arterial peak
      systolic gradient in adults having aortic valve replacement for isolated aortic
      valve stenosis.
AB  - Correlation of the structure of the operatively excised aortic valve with various
      clinical variables has received relatively little attention. This report
      describes certain observations in 115 patients aged >30 years (mean age 70) who
      had aortic valve replacement for aortic valve stenosis unassociated with mitral
      valve dysfunction. The operatively excised aortic valve was congenitally
      unicuspid in 3 patients (3%), congenitally bicuspid in 54 patients (47%),
      tricuspid in 57 patients (50%), and of uncertain structure in 1. Of the 87
      patients (76%) aged > or =65 years (Medicare population), 36 (41%) had
      congenitally malformed valves (bicuspid in each), and of the 28 patients (24%)
      aged <65 years, 21 (75%) had congenitally malformed valves. A higher percentage
      of patients with congenitally malformed valves had peak systolic pressure
      gradients across the valve >50 mm Hg than did patients with tricuspid valves (57%
      vs 43%). Concomitant coronary artery bypass grafting (CABG) was performed in 52
      patients (45%) (34 men and 18 women), and they had average peak systolic pressure
      gradients across the valve significantly lower than patients without coronary
      bypass (46 vs 64 mm Hg): 39% of the 57 patients with congenitally malformed
      valves and 53% of the 57 patients with tricuspid valves had concomitant coronary
      bypass (insignificant difference). Thus, in a relatively older population of 115
      patients having aortic valve replacement for isolated aortic valve stenosis, with
      or without associated aortic regurgitation, one half had congenitally malformed
      valves (either unicuspid or bicuspid valves) and one half had tricuspid valves.
      Patients having concomitant CABG had significantly smaller gradients across the
      stenotic valves than those who had no CABG.

PMID- 9193018
TI  - Gestational age- and growth-related alterations in fetal right and left
      ventricular diastolic filling patterns.
AB  - To evaluate the effects of gestational age on left and right ventricular
      diastolic filling in human fetuses, we retrospectively reviewed the diastolic
      flow velocity patterns through mitral and tricuspid valves in 307 normal fetuses
      aged 17 to 39 weeks' gestation. The subjects were divided into 3 age groups; 17
      to 24 weeks, 25 to 31 weeks, and 32 to 39 weeks. The variables measured were peak
      flow velocities of early diastole (peak E wave), of atrial contraction (peak A
      wave), and the velocity ratio (peak E/A ratio). As a whole, the transmitral peak
      E wave and peak E/A ratio correlated with age using a second-order polynomial
      curve fit. The strength of the linear correlation between age and transmitral
      peak E wave and peak E/A ratio and the slope of the relation were greater in the
      group aged 32 to 39 weeks than in group aged 25 to 31 weeks. Similar temporal
      change was observed in the relation between age, transtricuspid peak E wave, and
      peak E/A ratio. The peak A wave for both atrioventricular valves showed little
      change with gestational age. Contrary to the accepted concept that fetal peak E
      wave and peak E/A ratio increases linearly with aging, this study shows that
      early diastolic filling increases mainly after 25 weeks' gestation. We speculate
      that the maturational changes in ventricular properties in human fetuses
      accelerate after midgestation.

PMID- 9193020
TI  - Usefulness of the admission electrocardiogram for identifying the infarct-related
      artery in inferior wall acute myocardial infarction.
AB  - We analyzed the admission electrocardiogram in 109 patients with inferior wall
      acute myocardial infarction in an attempt to determine the infarct-related artery
      (IRA). The presence of ST depression in leads V1 or V2 had a high sensitivity for
      predicting the left circumflex artery as the IRA. The lack of ST depression in V1
      or V2 had a high negative predictive value for excluding the left circumflex
      artery as the IRA.

PMID- 9193019
TI  - Gender-specific differences in the QT interval and the effect of autonomic tone
      and menstrual cycle in healthy adults.
AB  - Gender differences in the corrected QT interval have been noted since Bazett's
      initial description during the 1920s. The mechanism of this gender difference is
      unknown, and this study was undertaken to evaluate potential autonomic and
      menstrual cycle effects on the QT interval. The study population consisted of a
      healthy volunteer sample of 23 women and 20 men. Twelve-lead electrocardiographic
      determinations were made at rest and following double autonomic blockade (with
      atropine and propranolol) during the menstrual, follicular, and luteal phases of
      the menstrual cycle. Men were studied during 3 separate visits as controls. The
      corrected QT interval at baseline tended to be longer in women than men (421 +/-
      16 ms vs 414 +/- 15 ms: p <0.07). Following double autonomic blockade, the
      corrected QT interval increased to 439 +/- 11 ms: p <0.001). However, the gender
      difference in corrected QT interval was unchanged (443 +/- 15 ms vs 437 +/- 12
      ms). At baseline, there was no significant difference in the corrected QT
      interval among the 3 phases of the menstrual cycle (421 +/- 10, 423 +/- 18, and
      420 +/- 18 in the menstrual, follicular, and luteal phases, respectively) and the
      corrected QT interval was longer in women than men at each visit. Following
      double autonomic blockade, the corrected QT interval in women was shorter in the
      luteal phase (438 +/- 16 ms) versus the menstrual (446 +/- 15 ms) or the
      follicular phase (444 +/- 13 ms; p <0.05). However, this difference, which was
      not present at baseline, does not appear to be responsible for the gender
      difference in the QT interval at rest. In conclusion, our results confirm that
      the corrected QT interval tends to be longer in women than men. Differences in
      autonomic tone and menstrual cycle variability in the corrected QT in women at
      rest do not appear to be responsible for the gender differences in the QT
      interval. The mechanism responsible for the longer QT interval in women remains
      to be defined.

PMID- 9193021
TI  - Therapeutic strategy with total coronary artery occlusions.
AB  - Patients with a coronary artery occlusion are more likely to be revascularized
      surgically or to be treated conservatively than patients without occlusion. A
      higher prevalence of patients with multivessel coronary artery disease (CAD),
      particularly with 3-vessel CAD, in the group with occlusion may account in part
      for this difference in management.

PMID- 9193022
TI  - Absence of correlation between coronary thrombosis and postatherectomy
      restenosis.
AB  - This study endeavored to assess whether thrombus in directional coronary
      atherectomy was correlated with later subsequent restenosis. We concluded that
      the presence of thrombus in native plaque is not correlated with the occurrence
      of postatherectomy restenosis.

PMID- 9193023
TI  - Effects of Palmaz-Schatz stents on angled coronary arteries.
AB  - This review of consecutive, single Palmaz-Schatz stent implantations reveals that
      coronary lesion angulation does not result in suboptimal results or increased
      restenosis after stenting. The implantation of a rigid stent at an arterial hinge
      point is associated with an increased restenosis rate.

PMID- 9193024
TI  - Reflection of epicardial U-wave changes in surface inferior electrocardiograms
      during inferoposterior or anterior wall myocardial ischemia.
AB  - The surface inferior electrocardiogram (ECG) has limited value for detecting
      frequently occurring epicardial U-wave changes over the ischemic inferoposterior
      wall. Reciprocal U-wave changes could occur in this ECG during anterior wall
      myocardial ischemia.

PMID- 9193025
TI  - Angioscopic coronary macromorphology after thrombolysis in acute myocardial
      infarction.
AB  - In addition to a disruption of yellow plaque, vasospasm may also play a role in
      thrombotic occlusions of coronary arteries in small cases of infarction.
      Macroscopic vascular injury and thrombus seemed to be unnecessary for vasospasm
      culminating in myocardial infarction.

PMID- 9193026
TI  - Preservation of autonomic function following successful reperfusion with
      streptokinase within 12 hours of the onset of acute myocardial infarction.
AB  - Successful reperfusion following thrombolysis results in increased heart rate
      variability in the first 24 hours after administration. Preservation of autonomic
      function may contribute to improved prognosis when coronary artery patency is
      restored with intravenous thrombolysis.

PMID- 9193027
TI  - Clinical predictors of defibrillation energy requirements.
AB  - In implantable cardioverter-defibrillator therapy with endocardial lead systems,
      certain clinical variables are associated with defibrillation energy
      requirements. Because of the weak correlation coefficients, these variables
      cannot predict defibrillation thresholds in individual patients.

PMID- 9193028
TI  - Utility and cost of event recorders in the diagnosis of palpitations, presyncope,
      and syncope.
AB  - In 184 patients given an event recorder for the evaluation of palpitations,
      syncope or presyncope, we found that event recorders are useful and relatively
      inexpensive in the initial evaluation of patients with palpitations regardless of
      the presence of heart disease, and of syncopal or presyncopal patients without
      heart disease. In patients with presyncope or syncope who have heart disease and
      a negative electrophysiology evaluation, event recorders have less utility and
      are more costly.

PMID- 9193029
TI  - Comparison of right ventricular outflow tract and apical lead permanent pacing on
      cardiac output.
AB  - Cardiac output was measured in 89 patients using transthoracic continuous-wave
      echo Doppler comparing right ventricular outflow tract pacing with the right
      ventricular apex at the time of permanent pacemaker implantation. Overall,
      cardiac output improved 18.8% (p <0.0001) and cardiac index 21.0% (p <0.0001)
      with outflow tract placement; patients with a lower baseline cardiac index had a
      greater percent improvement with outflow tract placement.

PMID- 9193030
TI  - Electrocardiographic features of septal location of right ventricular outflow
      tract tachycardia.
AB  - A consistent 12-lead electrocardiogram (ECG) morphology and characteristic
      frontal plane axis shift from sinus rhythm to ventricular tachycardia (VT) was
      demonstrated in 10 consecutive patients with idiopathic right ventricular outflow
      tract (RVOT) VT. All arrhythmias were successfully ablated on the septal side of
      the RVOT.

PMID- 9193031
TI  - Course and prognosis in patients > or = 70 years of age with congestive heart
      failure and normal versus abnormal left ventricular ejection fraction.
AB  - In this study of 501 patients aged > or =70 years hospitalized with congestive
      heart failure, 34.1% had normal left ventricular systolic function. Reduced left
      ventricular ejection fraction was an independent predictor of an adverse
      prognosis at 3 months but not at 1 year.

PMID- 9193032
TI  - Contribution of left atrial pressure and dimension to signal-averaged P-wave
      duration in patients with chronic congestive heart failure.
AB  - In a group of patients with chronic heart failure, a longer P-wave duration on
      signal-averaged electrocardiogram was found in those patients with higher
      pulmonary capillary wedge pressure, whereas the left atrium end-systolic diameter
      was not significantly different. Furthermore, an acute reduction in pulmonary
      capillary wedge pressure induced by sodium nitroprusside infusion was associated
      with a reduction in P-wave duration.

PMID- 9193033
TI  - Assessment of flail mitral leaflets by dynamic three-dimensional
      echocardiographic imaging.
AB  - To evaluate the usefulness of dynamic 3-dimensional images obtained by multiplane
      transesophageal echocardiography (TEE) in the diagnosis of the involved leaflets
      in patients with a flail mitral leaflet, 23 patients who underwent mitral valve
      repair were examined with multiplane TEE. In all patients, the involved lesions
      diagnosed by dynamic 3-dimensional images coincided with those confirmed at the
      time of operation; dynamic 3-dimensional images by multiplane transesophageal
      probe are useful in the evaluation of the involved sites in patients with a flail
      mitral leaflet.

PMID- 9193034
TI  - Is mitral valve prolapse a congenital or acquired disease?
AB  - The prevalence of mitral valve prolapse (MVP) at birth was studied in 1,734
      consecutive newborns without congenital structural heart disease. We have not
      identified any case of an unequivocal pattern of MVP using auscultatory and
      echocardiographic diagnostic criteria. Our data argue for the concept that MVP is
      an acquired disease.

PMID- 9193036
TI  - Optimal Albunex dosing for enhancement of Doppler tricuspid regurgitation
      spectra.
AB  - Intravenous albunex was more effective than agitated saline in enhancing
      incomplete Doppler echocardiography spectra for tricuspid regurgitation without a
      significant alteration in the maximal detected velocity. The optimal dose was 1
      to 4 ml in most patients, using an initial dose of 1 ml and titrating further
      dosing on the basis of the initial contrast effect.

PMID- 9193035
TI  - Transcatheter fenestration dilation and/or creation in postoperative Fontan
      patients.
AB  - There are very few therapeutic options for severely symptomatic Fontan patients
      after spontaneous complete or virtual fenestration closure. Its reopening in 14
      such patients led to dramatic hemodynamic improvement in most. The clinical
      experience with transcatheter fenestration creation and/or dilation in
      symptomatic Fontan patients is reported demonstrating feasibility, safety, and a
      novel management option for these patients.

PMID- 9193037
TI  - Measurement of coronary blood flow velocity during handgrip exercise using breath
      hold velocity encoded cine magnetic resonance imaging.
AB  - Coronary blood flow velocity was measured during handgrip exercise using breath
      hold velocity encoded cine magnetic resonance imaging. Peak diastolic coronary
      flow velocity in the left anterior descending artery was 20.6 +/- 9.3 cm/s (mean
      +/- SD) at baseline and increased significantly to 31.1 +/- 16.4 cm/s after
      exercise (50.7 +/- 31.3% increase, p <0.01).

PMID- 9193038
TI  - Usefulness of myocardial velocity gradient derived from two-dimensional tissue
      Doppler imaging as an indicator of regional myocardial contraction independent of
      translational motion assessed in atrial septal defect.
AB  - Independence of myocardial velocity gradient from translational motion of the
      heart was tested by comparing normal subjects and patients with atrial septal
      defect. Myocardial velocity gradient obtained from patients fit within the normal
      range, even though the translation of the left ventricle was exaggerated in
      patients, demonstrating the translation independence of myocardial velocity
      gradient in clinical settings.

PMID- 9193039
TI  - Abnormal ventricular repolarization mimicking myocardial infarction after
      heterocyclic antidepressant overdose.
AB  - In 2 young adult women who experienced acute heterocyclic antidepressant
      intoxication, we found a quite unusual electrocardiographic pattern characterized
      by abnormal ST-tract elevation in the right precordial leads associated with a
      marked QRS widening (right bundle branch block and left anterior fascicular block
      type). Because serum electrolyte imbalance and acute myocardial ischemic events
      were excluded, the mechanism by which antidepressant overdose may produce such
      elevation of the ST tract remains unclear.

PMID- 9193040
TI  - A genetic assessment of trisomy 21 in a patient with persistent truncus
      arteriosus who died 38 years ago.
AB  - A newborn baby with the unique combination of Down syndrome and persistent
      truncus arteriosus with interrupted aortic arch is described. The diagnosis of
      trisomy 21 was assessed 38 years after the patient's death by means of
      fluorescent in situ hybridization.

PMID- 9193041
TI  - Speech perception as pattern recognition.
AB  - This work provides theoretical and empirical arguments in favor of an approach to
      phonetics that is called double-weak. It is so called because it assumes
      relatively weak constraints both on the articulatory gestures and on the auditory
      patterns that map phonological elements. This approach views speech production
      and perception as distinct but cooperative systems. Like the motor theory of
      speech perception, double-weak theory accepts that phonological units are
      modified by context in ways that are important to perception. It further agrees
      that many aspects of such context dependency have their origin in natural
      articulatory processes. However, double-weak theory sides with proponents of
      auditory theories of phonetics by accepting that the real-time objects of
      perception are well-defined auditory patterns. Because speakers find ways to
      "orderly" output conditions" (Sussman et al., 1995), listeners are able to
      successfully decode speech using relatively simple pattern-recognition
      mechanisms. It is suggested that this situation has arisen through a stylization
      of gestural patterns to accommodate real-time limits of the perceptual system.
      Results from a new perceptual experiment, involving a four-dimensional stimulus
      continuum and a 10-category/hVC/response set, are shown to be largely compatible
      with this framework.

PMID- 9193042
TI  - Comparison between subjective and objective measures of active hearing protector
      and communication headset attenuation.
AB  - A masked-threshold and a loudness-balance method have been developed to estimate
      the attenuation of communication headsets and hearing protectors with built-in
      active noise reduction (ANR) systems. Both methods are used to estimate the
      attenuation of the ANR systems and the masked-threshold method is also used to
      estimate the total attenuation (active plus passive) of the device. The
      procedures are designed to be used in the presence of environmental noise, and to
      minimize the noise exposure of subjects during the measurements. For comparison,
      physical measurements of insertion loss have also been performed using a
      miniature microphone in the concha. Experiments showed that the masked-threshold
      methods tends to give increased estimates of the attenuation if the noise
      reduction of the left and right earcup ANR systems differs, as commonly occurs in
      practice. In contrast, the loudness-balance method reduces the estimates of the
      active attenuation. Insertion loss measurements may be influenced by the position
      of the microphone, owing to the spatial variability of the sound field under an
      earmuff when the ANR system is operating. Differences between physical and
      subjective measurements of up to 20 dB have been obtained in this study at
      frequencies of 250 Hz and below for a device in which the sound pressure varied
      substantially near, and within, the ear canal.

PMID- 9193043
TI  - Quantitative measures of hair cell loss in CBA and C57BL/6 mice throughout their
      life spans.
AB  - The CBA mouse shows little evidence of hearing loss until late in life, whereas
      the C57BL/6 strain develops a severe and progressive, high-frequency
      sensorineural hearing loss beginning around 3-6 months of age. These functional
      differences have been linked to genetic differences in the amount of hair cell
      loss as a function of age; however, a precise quantitative description of the
      sensory cell loss is unavailable. The present study provides mean values of inner
      hair cell (IHC) and outer hair cell (OHC) loss for CBA and C57BL/6 mice at 1, 3,
      8, 18, and 26 months of age. CBA mice showed little evidence of hair cell loss
      until 18 months of age. At 26 months of age, OHC losses in the apex and base of
      the cochlea were approximately 65% and 50%, respectively, and IHC losses were
      approximately 25% and 35%. By contrast, C57BL/6 mice showed approximately a 75%
      OHC and a 55% IHC loss in the base of the cochlea at 3 months of age. OHC and IHC
      losses increased rapidly with age along a base-to-apex gradient. By 26 months of
      age, more than 80% of the OHCs were missing throughout the entire cochlea;
      however, IHC losses ranged from 100% near the base of the cochlea to
      approximately 20% in the apex.

PMID- 9193044
TI  - Fine structure of the 2 f1-f2 acoustic distortion products: effects of primary
      level and frequency ratios.
AB  - The fine structure of the 2 f1-f2 acoustic distortion product (ADP) was measured
      in humans with different primary level (L1/L2) and frequency (f2/f1, f2 > f1)
      ratios. The (L1/L2) ratio was varied under two conditions. In the first condition
      L1 was fixed at 50 dB SPL while L2 was varied from 30 to 75dB SPL in 5-dB steps.
      An upward frequency shift was observed in the ADP fine structure as L2 was
      increased. In the second condition, L2 was fixed at 50 dB SPL and L1 varied, and
      a downward frequency shift was observed. These opposing frequency shifts are
      predicted by a vector-sum model [Sun et al., J. Acoust., Soc. Am. 96, 2166-2174,
      2175-2183 (1994)] and support the hypothesis that the ADP fine structure largely
      reflects place features of the area of overlap of the primary traveling waves.
      The mechanisms underlying the shifts in fine structure were further investigated
      by using three primary f2/f1 ratios: 1.11, 1.2, and 1.33. An orderly difference
      in the rate of fine-structure shift with level was observed as a function of
      f2/f1 ratio, with the largest rate of shift associated with the smallest
      frequency ratio. This observation, along with the fact that downward frequency
      shift (with L1 varied) is always at a larger rate than the upward shift (with L2
      varied), suggests that ADP levels and fine structure are strongly influenced by
      the nonlinear compression present in the mechanics of the basilar membrane in the
      region of overlap between the primary traveling waves.

PMID- 9193045
TI  - Changes in evoked otoacoustic emissions in the guinea pig after pure-tone
      acoustic overstimulation.
AB  - To test if click-evoked otoacoustic emissions (CEOAEs) have frequency
      specificity, continuous changes in CEOAEs (especially frequency components of the
      CEOAE power spectrum) after pure-tone exposure in guinea pigs were examined. Pure
      tone stimuli (0.5 kHz, 120 dB SPL; 2 kHz, 115 dB SPL; 4 kHz, 110 dB SPL) were
      given in a closed system for 3 min. After exposure, the frequency components in
      the CEOAE power spectrum decreased maximally at one-half octave or more above the
      overstimulation frequency. They partially recovered 2 h after exposure. The time
      course of compound action potential (CAP) thresholds after exposure was similar
      to that of the frequency components of the CEOAE power spectrum. It was concluded
      that some local damage caused by outer hair-cell dysfunction in the guinea pig
      cochlea can be detected by measuring shifts in frequency components in the CEOAE
      power spectrum.

PMID- 9193046
TI  - The mechanical waveform of the basilar membrane. I. Frequency modulations
      ("glides") in impulse responses and cross-correlation functions.
AB  - The purpose of this investigation is to present evidence from experimental as
      well as model results on temporal variations of the frequency of oscillation in
      the basilar membrane's impulse response. Stimuli were either clicks leading to a
      direct estimate of the impulse response, or bands of pseudo-random noise (one or
      two octaves wide) which lead to an indirect estimate of the impulse response via
      a cross-correlation procedure. The noise bands were centered at the best
      frequency of the BM location under observation. Responses were obtained from the
      basal turn of the guinea-pig cochlea, from a location with a best frequency (for
      the weakest stimuli) between 17.0 and 18.5 kHz. Data acquisition was done with a
      sample frequency of 208 kHz. Input-output cross-correlation functions were found
      to share with impulse responses the property that the initial oscillations have a
      noticeably lower frequency than the later ones. During the impulse response the
      frequency of oscillation increases gradually. This increase occurs and continues
      to beyond the time that the oscillations reach the largest amplitude. This
      frequency variation is called a "glide." Using the "analytic signal" method the
      frequency of oscillation is found to increase continually throughout the duration
      of the main lobe of oscillation, even at the lowest tested stimulus intensities
      (about 20 dB SPL). At high stimulus intensity both the direct and indirect
      impulse response change their appearance drastically but the glide retains its
      basic form. In the case of the direct impulse response estimate the glide can be
      attributed to temporal variation of the degree of nonlinearity. For the indirect
      impulse response this is not true, because with a constant level noise stimulus
      there is no regular temporal variation of nonlinearity. In this case the glide
      should be interpreted as an intrinsic property of the cochlear system. From our
      and others' data the glide was found to exist over a topographic frequency range
      of best frequencies of at least from 1.76 to 18 kHz. Two examples of present-day
      models of the cochlea are discussed of which one is found to demonstrate the
      glide phenomenon in its response, and the other one does not.

PMID- 9193047
TI  - Fluid-structure interaction of the stereocilia bundle in relation to
      mechanotransduction.
AB  - Current hypotheses regarding mechanotransduction rely upon motion of the
      stereocilia relative to the apical surface of the hair cell. The viscosity of the
      surrounding endolymphatic fluid will, however, attenuate stereocilia motion at
      higher frequencies of excitation. To investigate stereocilia motion for
      physiologically reasonable deflections and frequencies of excitation, the fluid
      structure interaction of the stereocilia bundle is considered analytically.
      Solutions in the frequency domain are determined for stereocilia bundle
      dimensions at several locations along the cochlear duct of the chinchilla.
      Results indicate that motion of the stereocilia is analogous to that of a low
      pass filter. Comparison of these solutions with Greenwood's frequency-place map
      demonstrates that motion of the stereocilia bundle exists without substantial
      attenuation at least up to frequencies appropriate for the location of the
      corresponding hair cell along the cochlear duct. The variation in stereocilia
      morphology within the mammalian cochlea thus appears to provide a collection of
      low-pass mechanoreceptors, arranged in order of increasing corner frequency
      across the auditory spectrum.

PMID- 9193048
TI  - Effects of acoustic trauma on the representation of the vowel "eh" in cat
      auditory nerve fibers.
AB  - A population study of cat auditory-nerve fibers was used to characterize the
      permanent deficits induced by exposure to 110-115 dB SPL, narrow-band noise.
      Fibers in the region of acoustic trauma (roughly 1-6 kHz) showed a loss of
      sensitivity at best frequency (BF) of about 50-60 dB and an increased tuning
      bandwidth. A correlation between weakened two-tone suppression and loss of
      sensitivity was found for fibers with BFs above 1 kHz. Single-fiber responses to
      the vowel "eh" were recorded at intensities ranging from near threshold to a
      maximum of about 110 dB SPL. In normal cochleas, the temporal response patterns
      show a capture phenomenon, in which the first two formant frequencies dominate
      the responses at high sound levels among fibers with BFs near the formant
      frequencies. After acoustic trauma, fibers in the region of threshold shift
      synchronized to a broad range of the vowel's harmonics and thus did not show
      capture by the second formant at any sound level used. The broadband nature of
      this response is consistent with the broadened tuning observed in the damaged
      fibers, but may also reflect a weakening of compressive nonlinearities
      responsible for synchrony capture in the normal cochlea.

PMID- 9193049
TI  - The modulated-unmodulated difference: effects of signal frequency and masker
      modulation depth.
AB  - The masked threshold for a signal is often times lower when the masker is
      modulated than when it is unmodulated. The difference in masked thresholds is
      referred to as the modulated-unmodulated difference, or MUD. The purpose of the
      present study was to follow up on the results of a previous study [Bacon et al.,
      J. Acoust. Soc. Am. 101, 1600-1610 (1997)] which showed that the MUD is larger
      for high than for low signal frequencies, both when the masker is no wider than a
      critical band (and the processing is solely within channel) and when it is
      broadband (and the processing may be both within and across channel). The present
      results indicate that the effects of signal frequency primarily exist only when
      the modulated masker is modulated at a depth greater than about 0.75, and that at
      these large depths, thresholds in the presence of the modulated masker are
      governed largely by forward masking. By far, the effect of signal frequency is
      larger with the broadband masker than with the critical-band masker, suggesting
      that there may be an across-channel process whose contribution is greater at high
      than at low signal frequencies. It is argued here that this across-channel
      process may be related to psychophysical suppression.

PMID- 9193050
TI  - Sensitivity to changes in overall level and spectral shape: an evaluation of a
      channel model.
AB  - Two experiments involving level and spectral shape discrimination which test an
      optimal channel model developed by Durlach et al. [J. Acoust. Soc Am. 80, 63-72
      (1986)] are described. The model specifies how the auditory system compares
      and/or combines intensity information in different frequency channels. In the
      first experiment, psychometric functions were obtained for the discrimination of
      changes in level and discrimination of changes in spectral shape for an eight
      tone complex sound. A variety of different base spectral shapes were tested. In
      some conditions, level randomization was introduced to reduce the reliability of
      across-interval changes in level. Increasing the amount of level variation
      degraded performance for the level discrimination task but had no effect on the
      shape discrimination task. In all conditions, sensitivity to changes in spectral
      shape was superior to sensitivity to changes in level. Consequently, two models
      of central noise are evaluated in an attempt to explain these results; one in
      which central noise acts prior to the formation of the likelihood ratio and one
      in which central noise degrades the likelihood ratio. The former model is more
      successful in accounting for the data. In a second experiment, the detectability
      of a level increment to one component of a multitone complex was measured. The
      frequency content of the complex was varied by systematically removing six
      components from a 23-component complex. Thresholds were measured for increments
      at three different signal frequencies. A common trend in the data was that when
      there was a spectral gap directly above the signal frequency, thresholds were
      lowest. This result differs from the predictions of a simple channel model, and
      contrasts with results presented by Green and Berg [Q. J. Exp. Psychol. 43A, 449
      458 (1991)].

PMID- 9193051
TI  - Excitation produced by Schroeder-phase complexes: evidence for fast-acting
      compression in the auditory system.
AB  - A series of experiments compared the excitation produced in an auditory filter
      centered on 1100 Hz by two complexes, both of which consisted of harmonics 2-20
      of a 100-Hz fundamental. When the components had a level of 69 dB SPL each,
      summing them in positive Schroeder phase produced substantially less forward
      masking of an 1100-Hz signal than when the components were summed in negative
      Schroeder phase. This difference decreased with decreases in overall masker
      level. Listeners also reported that the components of the positive-phase masker
      close to 1100 Hz were quieter than the corresponding components in the negative
      phase masker. The data are explained using Kohlrausch and Sander's [J. Acoust.
      Soc. Am. 97, 1817-1829 (1995)] finding that the response of an 1100-Hz auditory
      filter to the positive-phase complex shows marked peaks and dips, whereas that to
      the negative-phase complex does not. It is argued that the peaks in the response
      to the positive-phase masker are attenuated by fast-acting compression in the
      auditory system, thereby reducing the excitation produced by that sound. It is
      also argued that, compared to the power functions commonly used to model "excess
      masking" and the growth of loudness, the present data reflect greater compression
      at high levels but less compression at low levels.

PMID- 9193052
TI  - Masking period patterns of Schroeder-phase complexes: effects of level, number of
      components, and phase of flanking components.
AB  - Masking period patterns (MPPs) were obtained for maskers consisting of harmonics
      2-20 of a 100-Hz fundamental. The signal was always a 5-ms 1100-Hz sinusoid
      presented 152, 154, 156, 158, or 160 ms after the start of a 400-ms masker.
      Experiment 1 replicated the finding that, for a masker level of 69 dB component,
      the shape of the MPP depended strongly on the phases of the components: Summing
      them in positive Schroeder phase led to a threshold variation of about 18 dB
      across the MPP, but summing them in negative Schroeder phase produced a flat MPP
      [A. Kohlrausch and A. Sander, J. Acoust. Soc. Am. 97, 1817-1829 (1995)]. Reducing
      the level of the positive-phase masker resulted in a systematic flattening of the
      MPP, whereas the negative-phase MPPs were flat both at high and at low levels.
      Experiment 2 showed that removing all components of a positive-phase masker
      except those close to the signal raised thresholds at the minimum of the MPP. In
      contrast, a similar manipulation applied to the negative-phase masker produced a
      uniform elevation of the MPP. Experiment 3 showed that an analogous effect could
      be obtained by manipulating the phases of masker components remote from the
      signal. It is shown that several features of the data can be simulated using a
      nonlinear model of the auditory periphery [C. Giguere and P.C. Woodland, J.
      Acoust. Soc. Am. 95, 331-342 (1994)].

PMID- 9193053
TI  - Auditory filters measured at neighboring center frequencies.
AB  - Auditory filters were derived in 20 normal-hearing human listeners at center
      frequencies (CFs) of 913, 1095, 3651, and 4382 Hz using the roex (p,r) method.
      Comparisons were made between slopes of the filters' skirts at the neighboring
      CFs with filter output levels of 45 and 70 dB. The same comparisons were made
      with regard to filter equivalent rectangular bandwidth (ERB). In the 1000-Hz
      region, the low-frequency slopes (Pl) of filters centered at 913 and 1095 Hz were
      significantly correlated at both stimulus levels, while the high-frequency slopes
      (Pu) were similar only at the high test level. In the 4000-Hz region, for
      sinusoids of 3651 and 4382 Hz, the level effect was clearer as both Pu and Pl
      values diverged at the low level but were related at high levels. The ERBs
      centered at the same CFs displayed a similar level dependence. At the stimulus
      level most likely to be affected by an active feedback mechanism, auditory
      filters centered at nearly the same frequency displayed quite distinct frequency
      selectivity, and this trend was stronger in the 4000-Hz region than the 1000-Hz
      region. The findings suggest that a saturating, active cochlear mechanism may not
      be distributed evenly, or contribute to peripheral tuning with equal
      effectiveness throughout the length of the partition.

PMID- 9193054
TI  - A behavioral measure of basilar-membrane nonlinearity in listeners with normal
      and impaired hearing.
AB  - This paper examines the possibility of estimating basilar-membrane (BM)
      nonlinearity using a psychophysical technique. The level of a forward masker
      required to mask a brief signal was measured for conditions where the masker was
      either at, or one octave below, the signal frequency. The level of the forward
      masker at masked threshold provided an indirect measure of the BM response to the
      signal, as follows. Consistent with physiological studies, it was assumed that
      the BM responds linearly to frequencies well below the characteristic frequency
      (CF). Thus the ratio of the slopes of the masking functions between a masker at
      the signal frequency and a masker well below the signal frequency should provide
      an estimate of BM compression at CF. Results obtained from normally hearing
      listeners were in quantitative agreement with physiological estimates of BM
      compression. Furthermore, differences between normally hearing listeners and
      listeners with cochlear hearing impairment were consistent with the physiological
      effects of damage to the cochlea. The results support the hypothesis that BM
      nonlinearity governs the nonlinear growth of the upward spread of masking, and
      suggest that this technique provides a straightforward method for estimating BM
      nonlinearity in humans.

PMID- 9193055
TI  - Short-term temporal integration: evidence for the influence of peripheral
      compression.
AB  - Thresholds for a 6.5-kHz sinusoidal signal, temporally centered in a 400-ms
      broadband-noise masker, were measured as a function of signal duration for
      normally hearing listeners and listeners with cochlear hearing loss over a range
      of masker levels. For the normally hearing listeners, the slope of the function
      relating signal threshold to signal duration (integration function) was steeper
      at medium masker levels than at low or high levels by a factor of nearly 2, for
      signal durations between 2 and 10 ms, while no significant effect of level was
      found for signal durations of 20 ms and more. No effect of stimulus level was
      found for the hearing-impaired listeners at any signal duration. For signal
      durations greater than 10 ms, consistent with many previous studies, the slope of
      the integration function was shallower for the hearing-impaired listeners than
      for the normally hearing listeners. However, for shorter durations, there was no
      significant difference in slope between the results from the hearing-impaired
      listeners and those from the normally hearing listeners in the high- and low
      level masker conditions. A model incorporating a compressive nonlinearity,
      representing the effect of basilar-membrane (BM) compression, and a short-term
      temporal integrator, postulated to be a more central process, can account well
      for changes in the short-term integration function with level, if it is assumed
      that the compression is greater at medium levels than at low or high levels by a
      factor of about 4. This is in reasonable agreement with physiological
      measurements of BM compression, and with previous psychophysical estimates.

PMID- 9193056
TI  - Amplitude modulation depth discrimination of a sinusoidal carrier: effect of
      stimulus duration.
AB  - Discrimination of the change in depth of sinusoidal amplitude modulation (AM) was
      investigated as a function of stimulus duration. The carrier frequency was 4000
      Hz, the standard modulation depth (m) was either 0.1, 0.18, or 0.3, and the
      modulation rate was either 10, 20, 40, or 80 Hz. For all standard depths and
      modulation rates, threshold (delta m) decreased by more than a factor o two as
      stimulus duration doubled from the shortest duration used up to a certain
      duration (critical duration), beyond which the threshold decreased only slightly
      or remained constant. The critical duration corresponded to about four cycles of
      modulation. Psychometric functions were measured for different stimulus durations
      to examine the extent to which a multiple-looks model could explain the present
      data. This model provided a reasonable prediction of the change in AM depth
      discrimination threshold as a function of stimulus duration.

PMID- 9193057
TI  - Detection of silent intervals between noises activating different perceptual
      channels: some properties of "central" auditory gap detection.
AB  - This article describes four experiments on gap detection by normal listeners,
      with the general goal being to examine the consequences of using noises in
      different perceptual channels to delimit a silent temporal gap to be detected. In
      experiment 1, subjects were presented with pairs of narrow-band noise sequences.
      The leading element in each pair had a center frequency of 2 kHz and the trailing
      element's center frequency was parametrically varied. Gap detection thresholds
      became increasingly poor, sometimes by up to an order of magnitude, as the
      spectral disparity was increased between the noise bursts that marked the gap.
      These data suggested that gap-detection performance is impoverished when the
      underlying perceptual timing operation requires a comparison of activity in
      different perceptual channels rather than a discontinuity detection within a
      given channel. In experiment 2, we assessed the effect of leading-element
      duration in within-channel and between-channel gap detection tasks. Gap detection
      thresholds rose when the duration of the leading element was less than about 30
      ms, but only in the between-channel case. In experiment 3, the gap-detection
      stimulus was redesigned so that we could probe the perceptual mechanisms that
      might be involved in stop consonant discrimination. The leading element was a
      wideband noise burst, and the trailing element was a 300-ms bandpassed noise
      centered on 1.0 kHz. The independent variable was the duration of the leading
      element, and the dependent variable was the smallest detectable gap between the
      elements. When the leading element was short in duration (5-10 ms), gap
      thresholds were close to 30 ms, which is close to the voice onset time that
      parses some voiced from unvoiced stop consonants. In experiment 4, the generality
      of the leading-element duration effect in between-channel gap detection was
      examined. Spectrally identical noises defining the leading and trailing edges of
      the gap were presented to the same or to different ears. There was a leading
      element duration effect only for the between channel case. The mean gap threshold
      was again close to 30 ms for short leading-element durations. Taken together, the
      data suggest that gap detection requiring a temporal correlation of activity in
      different perceptual channels is a fundamentally different task to the
      discontinuity detection used to execute gap detection performance in the
      traditional, within-channel paradigm.

PMID- 9193059
TI  - Further studies of phonation threshold pressure in a physical model of the vocal
      fold mucosa.
AB  - This paper reports results of further experimentation on a previously developed
      physical model of the vocal-fold mucosa [Titze et al., J. Acoust. Soc. Am. 97,
      3080-3084 (1995)]. The effects of vocal-fold thickness, epithelial membrane
      thickness, and prephonatory glottal geometry on phonation threshold pressure were
      studied. Phonation threshold pressures in the range of 0.13 to 0.34 kPa were
      observed for an 11-mm-thick vocal fold with a 70-micron-thick "epithelial"
      membrane for different "mucosal" fluid viscosities. Higher threshold pressure was
      always obtained for thinner vocal folds and thicker membranes. In another set of
      experiments, lowest offset threshold pressure was obtained for a rectangular or a
      near-rectangular prephonatory glottis (with a glottal convergence angle within
      about +/- 3 degrees). It ranged from 0.07 to 0.23 kPa for different glottal half
      widths between 2.0 and 6.0 mm. The threshold for more convergent or divergent
      glottal geometries was consistently higher. This finding only partially agrees
      with previous analytical work which predicts a lowest threshold for a divergent
      glottis. The discrepancy between theory and data is likely to be associated with
      flow separation from a divergent glottis.

PMID- 9193058
TI  - Psychometric functions and temporal integration in electric hearing.
AB  - Temporal-integration functions and psychometric functions for detection were
      obtained in eight users of the Nucleus 22-electrode cochlear implant. Stimuli
      were 100-Hz, 200-microseconds/phase trains of biphasic pulses with durations
      ranging from 0.44 to 630.4 ms (1 to 64 pulses). Temporal-integration functions
      were measured for 21 electrodes. Slopes of these functions were considerably
      shallower than the 2.5 dB/doubling slopes typically observed in acoustic hearing.
      They varied widely across subjects and for different electrodes in a given
      subject, ranging from 0.06 to 1.94 dB/doubling of stimulus pulses, with a mean
      [standard deviation (s.d.)] value of 0.42 (0.38). Psychometric functions were
      measured for 11 of the same 21 electrodes. Slopes of psychometric functions also
      varied across subjects and electrodes, and were 2-20 times steeper than those
      reported by other investigators for normal-hearing and cochlear-impaired acoustic
      listeners. Slopes of individual psychometric functions for 1-, 2-, 4-, and 8
      pulse stimuli ranged from 0.20 to 1.84 log d'/dB with a mean (s.d.) value of 0.77
      (0.45). Psychometric-function slopes did not vary systematically with stimulus
      duration in most cases. A clear inverse relation between slopes of psychometric
      functions and slopes of temporal-integration functions was observed. This
      relation was reasonably well described by a hyperbolic function predicted by the
      multiple-looks model of temporal integration [Viemeister and Wakefield, J.
      Acoust. Soc. Am. 90, 858-865 (1991)]. Psychometric-function slopes tended to
      increase with absolute threshold and were inversely correlated with dynamic
      range, suggesting that observed differences in psychometric-function slopes
      across subjects and electrodes may reflect underlying differences in neural
      survival.

PMID- 9193060
TI  - Articulatory strengthening at edges of prosodic domains.
AB  - In this paper it is shown that at the edges of prosodic domains, initial
      consonant and final vowels have more extreme (less reduced) lingual
      articulations, which are called articulatory strengthening. Linguopalatal contact
      for consonants and vowels in different prosodic positions was compared, using
      reiterant-speech versions of sentences with a variety of phrasings read by three
      speakers of American English. Four prosodic domains were considered: the
      phonological word, the phonological (or intermediate) phrase, the intonational
      phrase, and the utterance. Domain-initial consonants show more linguopalatal
      contact than domain-medial or domain-final consonants, at three prosodic levels.
      Most vowels, on the other hand, show less linguopalatal contact in domain-final
      syllables compared to domain-initial and domain-medial. As a result, the
      articulatory difference between segments is greater around a prosodic boundary,
      increasing the articulatory contrast between consonant and vowels, and prosodic
      domains are marked at both edges. Furthermore, the consonant initial
      strengthening is generally cumulative, i.e., the higher the prosodic domain, the
      more linguopalatal contact the consonant has. However, speakers differed in how
      many and which levels were distinguished in this way. It is suggested that this
      initial strengthening could provide an alternative account for previously
      observed supralaryngeal declination of consonants. Acoustic duration of the
      consonants is also affected by prosodic position, and this lengthening is
      cumulative like linguopalatal contact, but the two measures are only weakly
      correlated.

PMID- 9193062
TI  - The characteristics of voicing in syllable-initial fricatives in American
      English.
AB  - This study investigated the acoustic characteristics of voicing in the production
      of fricative consonants. The fricatives [f v s z] were used in combination with
      the vowels [i e a o u] to create CV syllables, which were produced by four
      subjects both in a context condition (following voiced and voiceless velar stops)
      and in isolation. Analyses were conducted of the time course of glottal
      excitation during the fricative noise interval in the voiced and voiceless
      fricative stimuli. Results showed that the patterns of voicing in the fricative
      noise interval were influenced by the voicing characteristics of preceding stop
      consonants. Nonetheless, these carryover coarticulatory effects were short-lived,
      influencing only the first 10's of ms of the following segment. Despite the
      influence of phonetic context on the patterns of voicing, an acoustic measure
      relating to the presence or absence of glottal excitation at the acoustic
      boundaries of the fricative noise reliably classified a majority (93%) of the
      fricative consonants in terms of the phonetic category of voicing. Thus, while
      phonetic context affected the patterns of glottal excitation in the fricative
      noise interval, it did not affect the criterial attribute associated with the
      phonetic category of voicing.

PMID- 9193061
TI  - Coarticulatory stability in American English /r/.
AB  - A number of different researchers have reported a substantial degree of
      variability in how American English /r/ coarticulates with neighboring segments.
      Acoustic and articulatory data were used to investigate this variability for
      speakers of "rhotic" American English dialects. Three issues were addressed: (1)
      the degree to which the F3 trajectory is affected by segmental context and
      stress, (2) to what extent the data support a "coproduction" versus a "spreading"
      model of coarticulation, and (3) the degree to which the major acoustic
      manifestation of American English /r/--the time course of F3--reflects tongue
      movement for /r/. The f3 formant trajectory durations were measured by automatic
      procedure and compared for nonsense words of the form /'waCrav/ and /wa'Crav/,
      where C indicates a labial, alveolar, or velar consonant. These durations were
      compared to F3 trajectory durations in /'warav/ and /wa'rav/. In addition,
      formant values in initial syllables of words with and without /r/ were examined
      for effects of intervening consonant contexts. Results indicated similar F3
      trajectory durations across the different consonant contexts, and to a lesser
      degree across stress, suggesting that coarticulation of /r/ can be achieved by
      overlap of a stable /r/-related articulatory trajectory with movements for
      neighboring sounds. This interpretation, and the concordance of F3 time course
      with tongue movement for /r/, was supported by direct measures of tongue movement
      for one subject.

PMID- 9193063
TI  - Speech recognition at simulated soft, conversational, and raised-to-loud vocal
      efforts by adults with cochlear implants.
AB  - Ten postlinguistically deaf adults who used the Nucleus Cochlear Implant System
      and SPEAK speech coding strategy responded to vowels, consonants, words, and
      sentences presented sound-only at 70, 60, and 50 dB sound-pressure level. Highest
      group mean scores were at a raised-to-loud level of 70 dB for consonants (73%),
      words (44%), and sentences (87%); the highest score for vowels (70%) was at a
      conversational level of 60 dB. Lowest group mean scores were at a soft level of
      50 dB for vowels (56%), consonants (47%), words (10%), and sentences (29%); all
      except subject 7 had some open-set speech recognition at this level. For the
      conversational level (60 dB), group mean scores for sentences and words were 72%
      and 29%, respectively. With this performance and sound-pressure level, it was
      observed that these subjects communicated successfully in a variety of listening
      situations. Given these subjects' speech recognition scores at 60 dB and the fact
      that 70 dB does not simulate the vocal effort used in everyday speaking
      situations, it is suggested that cochlear implant candidates and implantees be
      evaluated with speech tests presented at 60 dB instead of the customary 70 dB
      sound-pressure level to simulate benefit provided by implants in everyday life.
      Analysis of individuals' scores at the three levels for the four speech materials
      revealed different patterns of speech recognition among subjects (e.g., subjects
      1 and 5). Future research on the relation between stimuli, sound processing, and
      subjects' responses associated with these different patterns may provide
      guidelines to select parameter values with which to map incoming sound onto an
      individual's electrical dynamic range between threshold and maximum acceptable
      loudness level to improve speech recognition.

PMID- 9193065
TI  - Increased Ac excision (iae): Arabidopsis thaliana mutations affecting Ac
      transposition.
AB  - The maize transposable element Ac is highly active in the heterologous hosts
      tobacco and tomato, but shows very much reduced levels of activity in
      Arabidopsis. A mutagenesis experiment was undertaken with the aim of identifying
      Arabidopsis host factors responsible for the observed low levels of Ac activity.
      Seed from a line carrying a single copy of the Ac element inserted into the
      streptomycin phosphotransferase (SPT) reporter fusion, and which displayed
      typically low levels of Ac activity, were mutagenized using gamma rays. Nineteen
      mutants displaying high levels of somatic Ac activity, as judged by their highly
      variegated phenotypes, were isolated after screening the M2 generation on
      streptomycin-containing medium. The mutations fall into two complementation
      groups, iae1 and iae2, are unlinked to the SPT::Ac locus and segregate in a
      Mendelian fashion. The iae1 mutation is recessive and the iae2 mutation is semi
      dominant. The iae1 and iae2 mutants show 550- and 70-fold increases,
      respectively, in the average number of Ac excision sectors per cotyledon. The
      IAE1 locus maps to chromosome 2, whereas the SPT::Ac reporter maps to chromosome
      3. A molecular study of Ac activity in the iae1 mutant confirmed the very high
      levels of Ac excision predicted using the phenotypic assay, but revealed only low
      levels of Ac re-insertion. Analyses of germinal transposition in the iae1 mutant
      demonstrated an average germinal excision frequency of 3% and a frequency of
      independent Ac re-insertions following germinal excision of 22%. The iae mutants
      represents a possible means of improving the efficiency of Ac/Ds transposon
      tagging systems in Arabidopsis, and will enable the dissection of host
      involvement in Ac transposition and the mechanisms employed for controlling
      transposable element activity.

PMID- 9193064
TI  - Effect of monaural and binaural altered auditory feedback on stuttering
      frequency.
AB  - The effect of monaural and binaural alterations in auditory feedback on
      stuttering frequency was investigated. Eleven participants who stutter read aloud
      under nonaltered auditory feedback (NAF) and monaural and binaural conditions of
      frequency altered feedback [(FAF), on-quarter octave shift upward] and delayed
      auditory feedback [(DAF), 50-ms delay] at a normal speech rate. Relative to the
      NAF condition, reductions in stuttering frequency of approximately 60%-75% were
      found with the altered auditory feedback conditions. Post hoc single-df
      comparisons revealed a reduction in stuttering frequency with altered auditory
      feedback versus NAF (p < 0.0001), a greater reduction in stuttering frequency for
      binaural compared to monaural altered auditory feedback (p = 0.028), and
      nonsignificant differences in stuttering frequencies for right versus left
      monaural conditions (p = 0.54) and DAF versus FAF (p = 0.70).

PMID- 9193066
TI  - Inefficient and incorrect processing of the Ac transposase transcript in iae1 and
      wild-type Arabidopsis thaliana.
AB  - As part of the analysis of the Arabidopsis mutant iae1-1 (increased Ac excision),
      quantitative studies of the Ac transposase transcript were conducted. The primary
      transcript of Ac contains three small introns (introns 1-3; mean size 89 bp) and
      one larger intron (intron 4; 387 bp). We analysed the splicing of intron 3 and
      intron 4 in wild-type Arabidopsis and the iae1-1 mutant. Our results demonstrate
      that the splicing of Ac introns 3 and 4 is inefficient (splicing efficiencies 57
      and 30% respectively) compared with that of an intron of an endogenous
      Arabidopsis gene (PHYB intron 1; splicing efficiency 90%). The poor splicing
      efficiency of Ac intron 4 was found to correlate with aberrant processing. Steady
      state levels of total Ac transcript were higher in the iae1-1 mutant than wild
      type, but the same aberrant processing occurred. The inefficient processing of Ac
      in Arabidopsis prompted us to construct an Ac element lacking introns (Ac::cDNA)
      in an attempt to increase transposition frequencies. Autonomous activity of the
      Ac::cDNA element was undetectable in Arabidopsis, despite its ability to
      transpose at high frequency in response to a strong transposase source
      (35S::transposase) in trans, and the demonstrable autonomy of the same element in
      tobacco. A number of smaller transcripts were detected in Arabidopsis lines
      containing Ac::cDNA or Ac. Analysis of these smaller transcripts revealed a high
      frequency of premature polyadenylation in exon 2 and splicing of cryptic introns.

PMID- 9193067
TI  - Alternative processing of the maize Ac transcript in Arabidopsis.
AB  - The successful application of the maize transposable element system Ac/Ds as a
      genome mutagen in heterologous plant species has recently proved the versatility
      and power of this technique in plant molecular biology. However, the frequency of
      Ac/Ds transposition is considerably lower in Arabidopsis thaliana than in most
      other dicot plant species that have been studied. Since previous research has
      established that transcripts derived from monocot genes can be alternatively
      processed in dicot plants, we have investigated both the efficiency of intron
      splicing and polyadenylation of the maize Ac transposase pre-mRNA in Arabidopsis
      thaliana, Nicotiana tabacum, Nicotiana plumbaginifolia and Zea mays. In this
      paper, we demonstrate that intron 4 is alternatively spliced within Arabidopsis,
      using cryptic 5' and 3'splice sites within the intron sequence, leading to a
      heterogeneous population of full length of transposase transcript. Furthermore,
      analysis of transposase transcript polyadenylation revealed that at least four
      alternative poly(A) sites were utilized between introns 2 and 3, resulting in
      truncated transposase transcripts. Finally, by Northern blotting, we established
      that the truncated transposase transcript was the most abundant form of
      transposase message in Arabidopsis. In contrast to these findings, the
      alternative splicing and premature polyadenylation of Ac message in Arabidopsis
      was unparalleled in the other species examined. We suggest that the poor
      frequency of transposition of Ac in Arabidopsis may be in part due to the low
      quantity of correctly processed transposase transcript available in this species.

PMID- 9193068
TI  - Integration of T-DNA binary vector 'backbone' sequences into the tobacco genome:
      evidence for multiple complex patterns of integration.
AB  - During the process of crown gall tumorigenesis, Agrobacterium tumefaciens
      transfers part of the tumor-inducing (Ti) plasmid, the T-DNA, to a plant cell
      where it eventually becomes stably integrated into the plant genome. Directly
      repeated DNA sequences, called T-DNA borders, define the left and the right ends
      of the T-DNA. The T-DNA can be physically separated from the remainder of the Ti
      plasmid, creating a 'binary vector' system; this system is frequently used to
      generate transgenic plants. Scientists initially thought that only those
      sequences located between T-DNA left and right borders transferred to the plant.
      More recently, however, several reports have appeared describing the integration
      of the non-T-DNA binary vector 'backbone' sequences into the genome of transgenic
      plants. In order to investigate this phenomenon, we constructed T-DNA binary
      vectors containing a nos-nptll gene within the T-DNA and a mas2'-gusA (beta
      glucuronidase) gene outside the T-DNA borders. We regenerated kanamycin-resistant
      transgenic tobacco plants and analyzed these plants for the expression of the
      vector-localized gusA gene and for the presence of binary vector backbone
      sequences. Approximately one-fifth of the plants expressed detectable GUS
      activity. PCR analysis indicated that approximately 75% of the plants contained
      the gusA gene. Southern blot analysis indicated that the vector backbone
      sequences could integrate into the tobacco genome linked either to the left or to
      the right T-DNA border. The vector backbone sequences could also integrate into
      the plant genome independently of (unlinked to) the T-DNA. Although we could
      readily detect T-strands containing the T-DNA within the bacterium, we could not
      detect T-strands containing only the vector backbone sequences or these vector
      sequences linked to the T-DNA.

PMID- 9193069
TI  - Intracellular localization of GBF proteins and blue light-induced import of GBF2
      fusion proteins into the nucleus of cultured Arabidopsis and soybean cells.
AB  - The G-box is an important regulatory element found in the promoters of many
      different genes. Four members of an Arabidopsis gene family encoding basic
      leucine zipper proteins (GBFs) which bind the G-box have previously been cloned.
      To study GBFs, a polyclonal antibody was raised against GBF1 expressed in
      bacteria. This antibody also recognized GBF2 and GBF3. Immunoblot analysis of
      nuclear and cytoplasmic fractions from Arabidopsis and soybean (SB-M) cell
      cultures indicated that over 90% of proteins detected with anti-GBF1 were
      cytoplasmic. Electrophoretic mobility shift assays indicated that over 90% of G
      box binding activity was cytoplasmic. DNA affinity chromatography demonstrated
      that each protein detected with anti-GBF1 specifically bound the G-box. To study
      individual GBFs, DNA constructs fusing GBF1, GBF2 and GBF4 to GUS were made and
      assayed by transient expression in SB-M protoplasts. Of GUS:GBF1 proteins, 50-62%
      were localized in the cytoplasm under all conditions tested, while 97% of
      GUS:GBF4 was localized in the nucleus. By contrast, whereas about 50% of GUS:GBF2
      was found in the cytoplasm of dark-grown cells, over 80% of this protein was
      found in the nucleus in cells cultured under blue light. Deletion analysis of
      GBF1 identified a region between amino acids 112 and 164 apparently required for
      cytoplasmic retention. These results suggest the intriguing possibility that
      limitation of nuclear access may be an important control on GBF activity. In
      particular, GBF2 is apparently specifically imported into the nucleus in response
      to light.

PMID- 9193070
TI  - Cell-cycle-regulated transcription of A- and B-type plant cyclin genes in
      synchronous cultures.
AB  - Synchronously dividing cell cultures of Catharanthus roseus were used to isolate
      cDNAs for two mitotic cyclins, named CYS and CYM. The deduced protein sequence of
      CYS is similar to that of A-type cyclins, and CYM belongs to the group of B-type
      cyclins. In a fashion similar to the pattern of expression seen for A-type and B
      type cyclins in mammalian cells, CYS is expressed before CYM in C. roseus cells
      during the cell cycle. CYS mRNA accumulated at the onset of S phase and
      disappeared early in the G2 phase, whereas CYM mRNA was detected in the G2 and M
      phases of the cell cycle. Tobacco homologs of the two genes showed similar cell
      cycle dependent expression patterns in synchronous cultures of tobacco BY2 cells.
      In both systems, CYS was expressed much earlier in the cell cycle than most other
      plant A-type cyclins, and hence CYS along with the soybean cyc1GM can be
      classified into a distinct subclass. The activities of CYM and CYS promoters
      during the cell cycle were analyzed in stably transformed tobacco BY2 cells.
      Cyclin promoter sequences of 0.5 kb could confer the typical cell-cycle-dependent
      expression to the beta-glucuronidase (GUS) reporter gene: the CYS promoter
      directed S-phase-specific expression, whereas the CYM promoter drove M-phase
      specific expression. These results indicate the important role of transcriptional
      regulation in the oscillations of cyclin mRNA levels during the cell cycle.

PMID- 9193071
TI  - Development of necrosis and activation of disease resistance in transgenic
      tobacco plants with severely reduced catalase levels.
AB  - Numerous studies argue that salicylic acid (SA) is an important component of the
      plant signal transduction pathway(s) leading to disease resistance. The discovery
      that the SA-binding protein is a catalase, whose activity is blocked by SA, led
      to the proposal that one of SA's modes of action is to inhibit this H2O2
      degrading enzyme and thus elevate H2O2 levels. To test this model, an attempt was
      made to mimic the action of SA by reducing the synthesis of catalase using
      antisense RNA technology. Analyses of transgenic tobacco plants that expressed
      the tobacco catalase 1 (cat1) or catalase 2 (cat2) gene in an antisense
      orientation indicate that there is no correlation between modest to high levels
      of reduction in catalase activity and activation of plant defenses such as
      pathogenesis-related (PR)-1 protein synthesis. However, three independent
      antisense catalase transgenic plants (ASCAT1 Nos 16, 17, and 28), which exhibited
      the most severe reduction in catalase activity (approximately 90% or more),
      developed chlorosis or necrosis on some of their lower leaves. These same leaves
      accumulated very high levels of PR-1 proteins and showed enhanced resistance to
      tobacco mosaic virus. Necrosis and elevated SA, which appear to result from
      severe depression of catalase levels, may be responsible for the induction of
      these defense responses.

PMID- 9193072
TI  - Ribosomal transcription units integrated via T-DNA transformation associate with
      the nucleolus and do not require upstream repeat sequences for activity in
      Arabidopsis thaliana.
AB  - Ribosomal repeat units of Arabidopsis thaliana were introduced into the A.
      thaliana genome via Agrobacterium-mediated transformation. Ribosomal transgenes
      integrated into chromosomal regions outside the nucleolus organizers. Cytological
      data suggest that the transgenes associate with a nucleolus. To allow detection
      of transgenic rRNA, a short extension was inserted into the V1 variable region of
      the 25S ribosomal gene. The RNA transcript from the transgene undergoes a series
      of maturation steps, including correct processing of the 5' end of 25S rRNA.
      Using primer extension analysis, expression of a complete rDNA repeat unit was
      compared with the activity of a repeat unit lacking a sequence called 'upstream
      Sal repeats'. No qualitative or quantitative differences were detected,
      suggesting that upstream repeat sequences of the rDNA intergenic region do not
      act as transcriptional enhancers for RNA polymerase L in A. thaliana.

PMID- 9193073
TI  - Independent modulation of Arabidopsis thaliana polyubiquitin mRNAs in different
      organs and in response to environmental changes.
AB  - The highly conserved protein ubiquitin is encoded by five polyubiquitin genes in
      Arabidopsis thaliana ecotype Columbia that have been divided into two subtypes,
      the UBQ3/UBQ4 subtype and the UBQ10/UBQ11/UBQ14 subtype. Northern analysis using
      gene-specific oligonucleotides as hybridization probes and enzyme activity
      measurements from transgenic plants expressing beta-glucuronidase (GUS) under the
      control of individual polyubiquitin 5' flanking regions were used to determine
      the development and environmental regulation of polyubiquitin transcription and
      mRNA accumulation. Polyubiquitin mRNA levels within and between subtypes were
      independently modulated. UBQ3 mRNA levels were three-fold higher than UBQ4 mRNA
      levels in vegetative organs, but only two-thirds of the UBQ4 mRNA levels in
      flowers. UBQ3 mRNA was modulated by dark/light treatments, while mRNAs from UBQ
      and all members of the other subtype were unaffected. Similarly, within the
      UBQ10/UBQ11/UBQ14 subtype, UBQ11/UBQ14 mRNAs were modulated differently in
      seedlings after a two-hour heat-shock treatment. Among all the polyubiquitin
      genes, UBQ10 mRNA level was the most constant in all organs and environmental
      conditions examined. Transgenic plants transformed with a UBQ10 5' flanking
      region::GUS gene contained higher levels of GUS activity than transgenic plants
      expressing GUS under the control of UBQ3 5' flanking regions. In conclusion, the
      relative abundance of different Arabidopsis polyubiquitin mRNAs, even those
      produced from highly similar genes within a subtype, appears to be modulated
      independently in response to developmental and environmental cues.

PMID- 9193074
TI  - Pollen-specific expression of DEFH125, a MADS-box transcription factor in
      Antirrhinum with unusual features.
AB  - MADS-box genes encode transcription factors that regulate different processes of
      early and late floral development. A novel type of MADS-box gene, DEFH125, was
      isolated from a stamen specific cDNA library from Antirrhinum majus. The DEFH125
      protein shows extensive similarity over the entire length to AGL17, a root
      specific MADS-box protein of Arabidopsis. By sharing amino acid deviations from
      the consensus MADS-box sequence not found in other MADS-box families, these two
      proteins constitute a novel MADS-box subfamily. However, in contrast to members
      of other subfamilies the overall structural similarity between the DEFH125 and
      AGL17 proteins does not coincide with a similarity of expression patterns and
      functions. The DEFH125 gene is expressed at detectable levels only in the third
      whorl when the meiotic division of the pollen mother cell is already
      accomplished. The DEFH125 protein has been located in the cytoplasm of the
      vegetative cell within the maturing pollen. Surprisingly, after pollination, the
      DEFH125 protein is also found in nuclei of cells within the transmitting tract of
      the carpel. The intriguing role of DEFH125, the first MADS-box transcription
      factor of this type, in aspects of fertilization, such as pollen maturation,
      pollen tube formation or pollen tube guidance in the carpel, is discussed.

PMID- 9193075
TI  - Azide-sensitive thylakoid membrane insertion of chimeric cytochrome f
      polypeptides imported by isolated pea chloroplasts.
AB  - Post-translational integration of cytochrome f into thylakoid membranes was
      observed after import by isolated pea chloroplasts of a chimeric protein
      consisting of the presequence of the small subunit of ribulose 1,5-bisphosphate
      carboxylase fused to the cytochrome f precursor. Import of a similar chimeric
      protein lacking the C-terminal 33 amino acid residues resulted in a soluble
      cytochrome f protein in the thylakoid lumen, indicating that the C-terminal
      region contains a stop-transfer sequence for membrane integration. Azide
      inhibited the insertion of cytochrome f into the thylakoid membrane, whereas the
      ionophores nigericin and valinomycin had little effect on membrane insertion. The
      precursor of the 33 kDa protein, but not the 23 kDa protein, of the photo-system
      II oxygen-evolving complex inhibited the thylakoid insertion of cytochrome f,
      suggesting competition for a component of the transport pathway. These
      experiments suggest that the post-translational insertion of cytochrome f into
      the thylakoid membrane uses a SecA-dependent pathway.

PMID- 9193076
TI  - Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus
      pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of
      provitamin A biosynthesis.
AB  - Rice (Oryza sativa L.), the major food staple for more than two billion people,
      contains neither beta-carotene (provitamin A) nor C40 carotenoid precursors
      thereof in its endosperm. To improve the nutritional value of rice, genetic
      engineering was chosen as a means to introduce the ability to make beta-carotene
      into rice endosperm tissue. Investigation of the biochemical properties of
      immature rice endosperm using [14C]-labelled substrates revealed the presence of
      geranyl geranyl diphosphate, the C20 general isoprenoid precursor necessary for
      C40 carotenoid biosynthesis. Phytoene synthase, which condenses two molecules of
      geranyl geranyl diphosphate, is the first of four specific enzymes necessary for
      beta-carotene biosynthesis in plants. Therefore, the Japonica rice model variety
      Taipei 309 was transformed by microprojectile bombardment with a cDNA coding for
      phytoene synthase from daffodil (Narcissus pseudonarcissus) under the control of
      either a constitutive or an endosperm-specific promoter. In transgenic rice
      plants, the daffodil enzyme is active, as measured by the in vivo accumulation of
      phytoene in rice endosperm. Thus, it is demonstrated for the first time that it
      is in principle possible to engineer a critical step in provitamin A biosynthesis
      in a non-photosynthetic, carotenoid-lacking plant tissue. These results have
      important implications for long-term prospects of overcoming worldwide vitamin A
      deficiency.

PMID- 9193078
TI  - Expression of a betaine aldehyde dehydrogenase gene in rice, a glycinebetaine
      nonaccumulator, and possible localization of its protein in peroxisomes.
AB  - Betaine aldehyde dehydrogenase (BADH) catalyzes the last step in the plant
      biosynthetic pathway that leads to glycinebetaine. Rice plants (Oryza sativa L.),
      albeit considered a typical non-glycinebetaine accumulating species, have been
      found to express this enzyme at low levels. This observation evokes an interest
      in phylogenic evolution of the enzyme in the plant kingdom. It is reported here
      that rice plants possess the ability to take up exogenously added betaine
      aldehyde through the roots and convert it to glycinebetaine, resulting in an
      enhanced salt-tolerance of the plants. A gene encoding a putative BADH from the
      rice genome was also cloned and sequenced. The gene was found to contain 14
      introns, and the overall nucleotide sequence of the coding region is c. 78%
      identical to that of the barley BADH cDNA. Cloning of a partial BADH cDNA from
      rice was accomplished by reverse transcription-polymerase chain reaction (RT
      PCR). The nucleotide sequence of the cloned fragment was found to be identical to
      the corresponding exon regions of the rice genomic BADH gene. The deduced amino
      acid sequences of rice and barley BADH both contain a C-terminal tripeptide SKL,
      a signal known to target preproteins to microbodies. This localization was
      confirmed by an immuno-gold labeling study of transgenic tobacco harboring barley
      cDNA, which showed BADH protein inside peroxisomes. Northern blot analysis
      revealed that the level of BADH mRNA is salt-inducible.

PMID- 9193077
TI  - PcMYB1, a novel plant protein containing a DNA-binding domain with one MYB
      repeat, interacts in vivo with a light-regulatory promoter unit.
AB  - Light regulatory unit 1 (LRU1) is necessary for and sufficient to mediate light
      dependent activation of the chalcone synthase (CHS) minimal promoter in
      Petroselinum crispum. This composite promoter unit consists of at least two
      distinct cis-acting elements, designated ACECHS and MRECHS, both of which are
      required for light induction. The ACGT-containing element ACECHS interacts with
      common plant regulatory factors (CPRFs) which belong to the basic region/leucine
      zipper (bZIP) class of transcription factors. Here, we demonstrate that MRECHS,
      originally identified as an in vivo DNA footprint, is a MYB recognition element.
      This element possesses a functional core that is essential for light
      responsiveness and is specifically recognized by two distantly related MYB-like
      proteins: MYB305 and the novel factor MYB1 from P. crispum. PcMYB1 was identified
      by both its specific binding to MRECHS in vitro and recognition of MRECHS in
      vivo. The deduced amino acid sequence revealed that PcMYB1 contains only one MYB
      like repeat. This portion of the protein constitutes the DNA-binding domain.
      Mutational analysis of PcMYB1 in combination with sequence comparison suggests
      the presence of a helix-turn-helix structure containing a recognition helix that
      is sufficient for sequence-specific binding. The structure of this distinct MYB
      like DNA-binding domain appears to be conserved in proteins from all three
      eukaryotic phyla.

PMID- 9193079
TI  - adg2-1 represents a missense mutation in the ADPG pyrophosphorylase large subunit
      gene of Arabidopsis thaliana.
AB  - Arabidopsis mutants affecting ADPG pyrophosphorylase (ADGase) activity can be
      divided into two complementation groups, adg1 and adg2. Previous biochemical
      studies of adg2-1 mutant indicated that mutant plants do not accumulate ADGase
      large subunit protein and that ADGase small subunits assemble as homotetramers.
      This suggested that the ADG2 gene may encode the large subunit of ADGase. In this
      paper, it is shown that adg2-1 mutant plants accumulate near wild-type levels of
      transcripts encoding both the large and small subunits of ADGase. However, by
      RFLP analysis and complementation of adg2-1 with the ADGase large subunit gene,
      we show that the adg2-1 mutant does represent a mutation of the ADGase large
      subunit gene. Sequence analysis of the adg2-1 allele revealed a missense
      mutation. The results therefore suggest either that the missense mutation affects
      the stability of the ADGase large subunit protein or that it prevents assembly of
      the large subunit into holoenzyme.

PMID- 9193080
TI  - Identification of members of gene families in Arabidopsis thaliana by contig
      construction from partial cDNA sequences: 106 genes encoding 50 cytoplasmic
      ribosomal proteins.
AB  - Partial cDNA sequencing to obtain expressed sequence tags (ESTs) has led to the
      identification of tags to about 8,000 of the estimated 20,000 genes on
      Arabidopsis thaliana. This figure represents four to five times the number of
      complete coding sequences from this organism available in international
      databases. In contrast to mammals, many proteins are encoded by multigene
      families in A. thaliana. Using ribosomal protein gene families as an example, it
      is possible to construct relatively long sequences from overlapping ESTs which
      are of sufficiently high quality to be able to unambiguously identify tags to
      individual members of multigene families, even when the sequences are highly
      conserved. A total of 106 genes encoding 50 different cytoplasmic ribosomal
      protein types have been identified, most proteins being encoded by at least two
      and up to four genes. Coding sequences of members of individual gene families are
      almost always very highly conserved and derived amino acid sequences are almost,
      if not completely, identical in the vast majority of cases. Sequence divergence
      is observed in untranslated regions which allows the definition of gene-specific
      probes. The method can be used to construct high-quality tags to any protein.

PMID- 9193084
TI  - Differential expression of the multigene family encoding the soybean
      mitochondrial alternative oxidase.
AB  - The alternative oxidase (AOX) of the soybean (Glycine max L.) inner mitochondrial
      membrane is encoded by a multigene family (Aox) with three known members. Here,
      the Aox2 and Aox3 primary translation products, deduced for cDNA analysis, were
      found to be 38.1 and 36.4 Kd, respectively. Direct N-terminal sequencing of
      partially purified AOX from cotyledons demonstrates that the mature proteins are
      31.8 and 31.6 KD, respectively, implying that processing occurs upon import of
      these proteins into the mitochondrion. Sequence comparisons show that the
      processing of plant AOX proteins occurs at a characteristic site and that the
      AOX2 and AOX3 proteins are more similar to one another than to other AOX
      proteins, including soybean AOX1. Transcript analysis using a polymerase chain
      reaction-based assay in conjunction with immunoblot experiments indicates that
      soybean Aox genes are differentially expressed in a tissue-dependent manner.
      Moreover, the relative abundance of both Aox2 transcripts and protein in
      cotyledons increase upon greening of dark-grown seedlings. These results
      comprehensively explain the multiple AOX-banding patterns observed on immunoblots
      of mitochondrial proteins isolated from various soybean tissues by matching
      protein bands with gene products.

PMID- 9193081
TI  - Importin alpha from Arabidopsis thaliana is a nuclear import receptor that
      recognizes three classes of import signals.
AB  - Protein import into the nucleus is a two-step process. In vitro import systems
      from vertebrate cell extracts have shown several soluble factors are required.
      One of these factors is the receptor importin alpha, which binds to nuclear
      localization signals (NLS) in vitro. We previously cloned an importin alpha
      homolog from Arabidopsis thaliana (At-IMP alpha) and demonstrated that this
      protein was not depleted from tobacco (Nicotiana tabacum) protoplasts after
      permeabilization of the plasma membrane, (Hicks et al., 1996). To determine if At
      IMP alpha is functional, we used an in vitro NLS-binding assay. We found that At
      IMP alpha is specific, and the receptor is able to recognize three classes of NLS
      identified in plants. Purified antibodies to At-IMP alpha were used to determine
      the in vivo location of importin alpha in tobacco protoplasts. Importin alpha is
      found in the cytoplasm and nucleus, and it is most highly concentrated at the
      nuclear envelope. The biochemical properties of nuclear importin alpha and
      localization studies using purified nuclei demonstrate that importin alpha is
      tightly associated with the plant nucleus. Moreover, these results suggest that a
      fraction of nuclear importin alpha interacts with the nuclear pore complex.

PMID- 9193085
TI  - Molecular cloning of the cowpea leghemoglobin II gene and expression of its cDNA
      in Escherichia coli. Purification and characterization of the recombinant
      protein.
AB  - Cowpea (Vigna unguiculata) nodules contain three leghemoglobins (LbI, LbII, and
      LbIII) that are encoded by at least two genes. We have cloned and sequenced the
      gene that encodes for LbII (lbII), the most abundant Lb in cowpea nodules, using
      total DNA as the template for PCR. Primers were designed using the sequence of
      the soybean lbc gene. The lbII gene is 679 bp in length and codes for a predicted
      protein of 145 amino acids. Using sequences of the cowpea lbII gene for the
      synthesis of primers and total nodule RNA as the template, we cloned a cDNA for
      LbII into a constitutive expression vector (pEMBL19+) and then expressed it in
      Escherichia coli. Recombinant LbII (rLbII) and native LbII (nLbII) from cowpea
      nodules were purified to homogeneity using standard techniques. Properties of
      rLbII were compared with nLbII by partially sequencing the proteins and by sodium
      dodecyl sulfate- and isoelectric focusing polyacrylamide gel electrophoresis,
      western-blot analysis using anti-soybean Lba antibodies, tryptic and chymotryptic
      mapping, and spectrophotometric techniques. The data showed that the structural
      and spectral characteristics of rLbII and nLbII were similar. The rLbII was
      reversibly oxygenated/deoxygenated, showing that it is a functional hemoglobin.

PMID- 9193088
TI  - Adenylosuccinate synthetase from maize. Purification, properties, and mechanism
      of inhibition by 5'-phosphohydantocidin.
AB  - Adenylosuccinate synthetase (AdSS) is the site of action hydantocidin, a potent
      microbial phytotoxin. A kinetic analysis of the mode of inhibition of a plant
      adenylosuccinate synthetase by the active metabolite 5'-phosphohydantocidin (5'
      PH) was the objective of the present study. AdSS was purified 5800-fold from
      maize (Zea mays), to our knowledge the first purification of the enzyme from a
      plant source. N-terminal sequencing established the cleavage site of the
      previously published deduced sequence of the initial transcript. The subunit
      molecular mass was determined to be 48 kD and the isoelectric point was at pH
      6.1. Values of the Michaelis constant for the three substrates IMP, GTP, and
      aspartate were 21, 16, and 335 microM, respectively. Inhibition of AdSS by 5'-PH
      was measurably time-dependent. The trace of the inactivation curve could not be
      altered by preincubating the enzyme and inhibitor in the absence of substrates
      but could be linearized by preincubating the enzyme with inhibitor, aspartate,
      GTP (or GDP), and inorganic phosphate. Inhibition of AdSS by 5'-PH was
      competitive with IMP, with an apparent Ki of 22 nM. Apparently, 5'-PH inhibits
      the enzyme by binding to the IMP site and forming a tight, dead-end complex.

PMID- 9193090
TI  - Negative regulation in the expression of a sugar-inducible gene in Arabidopsis
      thaliana. A recessive mutation causing enhanced expression of a gene for beta
      amylase.
AB  - Expression of a beta-amylase gene of Arabidopsis thaliana (AT beta-Amy) is
      regulated by sugars. We identified a mutant, hba1, in which the level of
      expression of AT beta-Amy in leaves of plants that had been grown in a medium
      with 2% sucrose was significantly higher than that in wild-type plants. Higher
      that wild-type levels of beta-amylase in hba1 plants depended on the presence of
      1 to 2% sucrose or 1% glucose in the medium, whereas leaves of mutant plants
      grown with higher levels of sugars had beta-amylase activities similar to those
      in leaves of wild-type plants. The hba1 phenotype was recessive and did not
      affect levels of sugars and starch in leaves. It is proposed that expression of
      AT beta-Amy is regulated by a combination of both positive and negative factors,
      dependent on the level of sugars, and that HBA1 might function to maintain low
      level expression of AT beta-Amy until the level of sugars reaches some high
      level. Results of crosses of hba1 plants with transgenic plants that harbored an
      AT beta-Amy:GUS transgene with 1587 bp of the 5'-upstream region suggested that
      HBA1 affects expressions of AT beta-Amy in trans. The hba1 plants also had growth
      defects and elevated levels of anthocyanin in their petioles. However, sugar
      related changes in levels of several mRNAs other than beta-amylase mRNA were
      unaffected in hba1 plants, suggesting that only a subset of sugar-regulated genes
      is under the control HBA1.

PMID- 9193092
TI  - Soybean root nodule acid phosphatase.
AB  - Acid phosphatases are ubiquitous enzymes that exhibit activity against a variety
      of substrates in vitro, although little is known about their intracellular
      function. In this study, we report the isolation, characterization, and partial
      sequence of the major acid phosphatase from soybean (Glycine max L.) root
      nodules. The phosphatase was purified predominantly as a heterodimer with
      subunits of 28 and 31 kD; homodimers of both subunits were also observed and
      exhibited phosphatase activity. In addition to the general phosphatase substrate,
      p-nitrophenyl phosphate, the heterodimeric form of the enzyme readily hydrolyzed
      5'-nucleotides, flavin mononucleotide, and O-phospho-L-Tyr. Low or negligible
      activity was observed with ATP or polyphosphate. Purified nodule acid phosphatase
      was stimulated by magnesium, inhibited by calcium and EDTA, and competitively
      inhibited by cGMP and cAMP with apparent Ki values of 7 and 12 microM,
      respectively. Partial N-terminal and internal sequencing of the nodule acid
      phosphatase revealed homology to the soybean vegetative storage proteins. There
      was a 17-fold increase in enzyme activity and a noticeable increase in protein
      levels detected by immunoblotting methods during nodule development. Both of
      these parameters were low in young nodules and reached a peak in mature,
      functional nodules, suggesting that this enzyme is important for efficient nodule
      metabolism.

PMID- 9193091
TI  - Proline accumulation and salt-stress-induced gene expression in a salt
      hypersensitive mutant of Arabidopsis.
AB  - The sos1 mutant of Arabidopsis thaliana is more than 20 times more sensitive to
      NaCl stress than wild type Arabidopsis. Because proline (Pro) is generally
      thought to have an important role in plant salt tolerance, the sos1 mutant and
      the wild type were compared with respect to their capacity to accumulate Pro
      under NaCl stress, and sos1 mutant plants accumulated more Pro than wild-type.
      The P5CS gene, which catalyzes the rate-limiting step in Pro biosynthesis, is
      induced by salt stress to a higher level in sos1 than in the wild type. Although
      a defective high-affinity K uptake system in sos1 causes K deficiency and
      inhibits growth in NaCl-treated plants, this decrease is not a sufficient signal
      for Pro accumulation and P5CS gene expression. Not all salt-stress-induced genes
      have a higher level of expression in sos1. The expression levels of AtPLC and
      RD29A, which encode a phospholipase C homolog and a putative protective protein,
      respectively, are the same in sos1 as in the wild type. However, the expression
      of AtMYB, which encodes a putative transcriptional factor, is induced to a much
      higher level by salt stress in sos1. Thus, the SOS1 gene product serves as a
      negative regulator for the expression of P5CS and AtMYB, but has no effect on
      AtPLC and RD29A expression.

PMID- 9193094
TI  - Evidence for transcriptional regulation of plastid photosynthesis genes in
      Arabidopsis thaliana roots.
AB  - Mechanisms underlying suppressed levels of transcripts for plastid photosynthesis
      genes in nongreen tissues such as roots and calli were analyzed in Arabidopsis
      thaliana, a plant suitable for further genetic dissection. A region encoding
      promoters of rbcL, the gene encoding the large subunit of ribulose-1,5
      biphosphate carboxylase/oxygenase, and the atpB/E operon for the beta and epsilon
      subunits of coupling factor one were cloned and sequenced. Transcripts for rbcL,
      atpB/E, and psbA, the gene for the D1 protein in the photosystem II reaction
      center, were barely detectable in roots of A. thaliana, whereas 16S rRNA was
      detected at a low level. The run-on transcription experiment revealed that
      expression of rbcL, atpB/E, and psbA was regulated at transcription. The copy
      number of plastid DNA in roots was one-fifth that in green leaves on the basis of
      total cellular DNA, suggesting that in the latter the DNA copy-number regulation
      also exists in plastid gene expression. Digestion of DNA with methyl-sensitive
      and -insensitive isoschizomeric endonucleases and subsequent polymerase chain
      reaction, as well as in vitro transcription of plastid DNAs with Escherichia coli
      RNA polymerase, resulted in no evidence of regulation by DNA modification. In
      spite of predominant suppression of expression of rbcL, atpB/E, and psbA at
      transcription in roots and calli, 16S rRNA levels were decreased because of low
      RNA stability.

PMID- 9193095
TI  - Antagonistic but complementary actions of phytochromes A and B allow seedling de
      etiolation.
AB  - Using dichromatic radiation, we show that the actions of phytochromes A and B
      (phyA and phyB) in Arabidopsis thaliana are antagonistic in mediating red and far
      red radiation effects on seedling de-etiolation and yet act in a complementary
      manner to regulate de-etiolation, irrespective of spectral composition. At low
      phytochrome photoequilibria inhibition of hypocotyl extension was strong, because
      of the action of a far-red high-irradiance response mediated by phyA. At high
      phytochrome photoequilibria inhibition of hypocotyl extension was also strong,
      because of the action of phyB. At intermediate photoequilibria hypocotyl
      inhibition was less strong. In their natural environment, this dual action will
      strongly retard hypocotyl growth and promote cotyledon opening and expansion both
      in open daylight and under dense vegetation. Overlapping action by phyA and phyB
      will substantially promote de-etiolation in sparse vegetation. The antagonistic
      and complementary actions of phyA and phyB, therefore, allow the optimum
      regulation of seedling growth after emergence from the soil.

PMID- 9193096
TI  - Light regulation of the abundance of mRNA encoding a nucleolin-like protein
      localized in the nucleoli of pea nuclei.
AB  - A cDNA encoding a nucleolar protein was selected from a pea (Pisum sativum)
      plumule library, cloned, and sequenced. The translated sequence of the cDNA has
      significant percent identity to Xenopus laevis nucleolin (31%), the alfalfa
      (Medicago sativa) nucleolin homolog (66%), and the yeast (Saccharomyces
      cerevisiae) nucleolin homolog (NSR1) (28%). It also has sequence patterns in its
      primary structure that are characteristic of all nucleolins, including an N
      terminal acidic motif, RNA recognition motifs, and a C-terminal Gly- and Arg-rich
      domain. By immunoblot analysis, the polyclonal antibodies used to select the cDNA
      bind selectively to a 90-kD protein in purified pea nuclei and nucleoli and to an
      88-kD protein in extracts of Escherichia coli expressing the cDNA. In
      immunolocalization assays of pea plumule cells, the antibodies stained primarily
      a region surrounding the fibrillar center of nucleoli, where animal nucleolins
      are typically found. Southern analysis indicated that the pea nucleolin-like
      protein is encoded by a single gene, and northern analysis showed that the
      labeled cDNA binds to a single band of RNA, approximately the same size and the
      cDNA. After irradiation of etiolated pea seedlings by red light, the mRNA level
      in plumules decreased during the 1st hour and then increased to a peak of six
      times the 0-h level at 12 h. Far-red light reversed this effect of red light, and
      the mRNA accumulation from red/far-red light irradiation was equal to that found
      in the dark control. This indicates that phytochrome may regulate the expression
      of this gene.

PMID- 9193098
TI  - Broad-range and binary-range acyl-acyl-carrier protein thioesterases suggest an
      alternative mechanism for medium-chain production in seeds.
AB  - In the current model of medium-chain (C8-14) fatty acid biosynthesis in seeds,
      specialized FatB acyl-acyl-carrier-protein (ACP) thioesterases are responsible
      for the production of medium chains. We have isolated and characterized FatB
      cDNAs from the maturing seeds of elm (Ulmus americana) and nutmeg (Myristica
      fragrans), which accumulate predominantly caprate (10:0)- and myristate (14:0)
      containing oils, respectively. In neither species were we able to find cDNAs
      encoding enzymes specialized for these chain lengths. Nutmeg FatB hydrolyses C14
      18 substrates in vitro and expression in Brassica napus seeds leads to an oil
      enriched in C14-18 saturates. Elm FatB1 displays a binary specificity: one
      activity is centered on 10:0-ACP, and a second is centered on palmitate (16:0)
      ACP. After expression in B. napus seeds the oil is enriched in C10-18 saturates,
      predominantly 16:0, 14:0, and 10:0. The composition of free fatty acids produced
      by elm FatB1 in Escherichia coli shifts from C14-16 to mostly C8-10 by increasing
      the rate of chain termination by this enzyme. These results suggest the existence
      of an alternative mechanism used in the evolution of medium-chain production, a
      model of which is presented.

PMID- 9193097
TI  - A nitrate-inducible ferredoxin in maize roots. Genomic organization and
      differential expression of two nonphotosynthetic ferredoxin isoproteins.
AB  - We have identified and characterized a nitrate-inducible ferredoxin (Fd) in maize
      (Zea mays L.) roots by structural analysis of the purified protein and by cloning
      of its cDNA and gene. In maize Fd isoproteins are encoded by a small multigene
      family, and the nitrate-inducible Fd was identified as a novel isoprotein,
      designated Fd VI, which differed from an Fd I to Fd V identified to date. In the
      roots of seedlings cultured without nitrate, Fd VI was undetectable. However,
      during the induction of the capacity for nitrate assimilation, the amount of Fd
      VI increased markedly within 24 h. Concurrently, the level of transcript for Fd
      VI increased, but more quickly, reaching a maximal level within 2 h with kinetics
      similar to those of nitrite reductase and Fd-NADP+ reductase. Fd III was
      constitutively expressed in roots, and no such changes at the protein and mRNA
      levels were observed during the nitrate induction. In the 5' flanking region of
      the gene for Fd VI only, we identified NIT-2 motifs, which are widely found in
      genes for enzymes related to nitrogen metabolism. These data indicate that Fd VI
      is co-induced with the previously characterized enzymes involved in nitrate
      assimilation, and they suggest that the novel Fd isoprotein, distinct from the
      constitutively expressed Fd, might play an important role as an electron carrier
      from NADPH to nitrite reductase and other Fd-dependent enzymes in root plastids.

PMID- 9193102
TI  - Plasmid stabilization by post-segregational killing.

PMID- 9193103
TI  - Pathways and genes involved in cellulose biosynthesis.

PMID- 9193104
TI  - Conjugative transposons.

PMID- 9193105
TI  - Termination of DNA replication in prokaryotic chromosomes.

PMID- 9193108
TI  - Specificity of receptor tyrosine kinase signaling pathways: lessons from
      Drosophila.

PMID- 9193109
TI  - Switching of gene expression: analysis of the factors that spatially and
      temporally regulate plant gene expression.
AB  - In this chapter, we have reviewed the present research and understanding of
      several families of transcription factors in plants. From this information, it
      appears there is good conservation between the types of transcription factors in
      plants and animals. However, there are several types of factors which have been
      isolated in plants that remain to be documented in animals (e.g., HD-Zip and GT).
      These as well as the presence of two types of TATA-binding proteins (TBPs) in
      plants suggest that although transcription in eukaryotes is highly conserved,
      fundamental differences may exist. Despite the differences, the modes of
      regulating transcription are well conserved. Figure 3 summarizes these modes of
      regulation. In recent years, the role of chromatin structure as well as
      subcellular localization have been the focus of a vast amount of research in
      mammals, Drosophila and yeast. However, very little research in these areas has
      been done in plants. Isolation of genes such as Curly leaf suggest a conservation
      of genes that influence the formation of heterochromatin-like structures. Whether
      or not this gene influences chromatin/heterochromatin structure in plants,
      however, remains to be tested. The study of nuclear localization of factors such
      as COP1 and KN1 is now leading to models for regulating nuclear transport as well
      as intercellular transport of transcription factors. Further study of the inter-
      and intracellular movement of these and other transcription factors may provide
      information on new modes of regulating transcription. In addition to
      understanding the role chromatin structure and subcellular localization of
      transcription factors may have on transcription initiation, the biological role
      of many plant transcription factors remains to be identified. Several approaches
      may be taken to understand the mechanisms by which transcription factors
      influence biochemical and physiological processes in the plant. These steps
      include 1) identification of the DNA-binding sites of the factors as well as the
      promoter regions which contain these sites. Presently, this approach is limiting
      in that not many non-coding regions have been sequenced and characterized in
      detail. Furthermore, the presence of a putative binding site within a promoter
      does not necessarily indicate that the factor will bind to the site in vivo. 2)
      Analysis of the binding affinity for a particular factor to a binding site in
      comparison to other related factors, via in vitro competition assays and
      quantitative titrations. This will provide information on how strongly these
      factors are binding to the sites, but without knowledge of all the factors
      present in a single cell it is difficult to recreate the in vivo conditions. 3)
      Generation of transgenic plants or microinjection of DNA/RNA to express a
      particular factor ectopically, reduce expression of the factor via antisense
      expression, and creation of dominant negative mutants by overexpression of key
      dimerization domains may provide information concerning what biological pathways
      these factors influence. 4) Isolation of mutations in particular transcription
      factors has been extremely informative in floral development. However, this
      approach usually entails isolation of a mutant due to a phenotype and eventual
      mutated locus. The cloning of the locus may or may not involve a transcription
      factor. 5) Many plant transcription factors have been isolated via sequence
      similarity to other previously identified and/or characterized transcription
      factors. However, the biological role of may of these factors is not known. In
      addition to ectopic expression of these factors by creating transgenic plants,
      isolation of a loss-of-function mutation may provide valuable information
      concerning the role of this factor in vivo. Many loss-of-function mutations in
      MADS box genes have led to a better understanding of how the MADS domain proteins
      interact with one another as well as how they influence floral development.
      (ABSTRACT TRUNCATED)

PMID- 9193110
TI  - Nucleic acid transport in plant-pathogen interactions.
AB  - Inter- and intracellular transport of nucleic acids during plant-pathogen
      interaction is described on the examples of cell-to-cell movement of plant
      viruses and nuclear import of Agrobacterium T-DNA. In both cases, the transport
      process is mediated by specialized proteins produced by the pathogen. Plant virus
      movement occurs through the intercellular connections, plasmodesmata. In this
      process, the viral genomic nucleic acid is bound by virus-encoded movement
      protein. The nucleoprotein complex is then targeted to plasmodesmata, potentially
      via interaction with the host cell cytoskeleton. Prior to translocation, the
      plasmodesmal channel is dilated by the movement of protein. Nuclear import of
      Agrobacterium T-DNA is also mediated by bacterial proteins associated with the
      transported nucleic acid molecule. Specifically, the VirD2 and VirE2 proteins
      complex with the transferred DNA, providing it with the nuclear localization
      signals (NLSs). The VirD2 NLS is an evolutionarily conserved signal, active both
      in plant and animal cells. In contrast, the VirE2 NLS is plant-specific. Both
      VirD2 and VirE2 NLSs most likely interact with the plant cell nuclear import
      machinery to initiate the transport process.

PMID- 9193112
TI  - Production and analysis of transgenic mice containing yeast artificial
      chromosomes.

PMID- 9193113
TI  - Comparative molecular analysis of genes for polycyclic aromatic hydrocarbon
      degradation.

PMID- 9193115
TI  - Depression, stressful life events, social support, and self-esteem in middle
      class African American women.
AB  - African American women, are at risk for development of depression because they
      are a racial minority and female, and often have multiple roles which affect
      their social supports and self-esteem. An exploratory study was conducted that
      examined relationships between depression, stressful life events, social support,
      and self-esteem in 100 middle class African American women aged 20 to 35 years.
      The conceptual framework for the study was derived from Beeber's (1987) model.
      Correlational analysis revealed a positive relationship between depression and
      stressful life events and a negative relationship between depression and social
      support. Regression analysis revealed that stressful life events and social
      support added significantly to the model whereas self-esteem did not.

PMID- 9193116
TI  - The experience of caring for an adult child with schizophrenia.
AB  - The experience of caring for an adult child with schizophrenia was explored using
      phenomenological methodology. Nine parents who were the primary caretakers of an
      adult child with schizophrenia participated in qualitative interviews. The
      resulting transcripts were analyzed to discover the structure of the lived
      experience. The study revealed that the diagnosis of schizophrenia in a child is
      experienced by the parent as a destructive force that interrupts and radically
      transforms the normative family life trajectory. This grief-filled experience
      involves both the loss of an imagined, idealized child and a transformation of
      the physically present child into a needy stranger. Implications are discussed
      and applied to community-based, family-centered mental health care. Importantly,
      the revealed dissatisfaction with initial mental health evaluations suggests that
      modification of current practices could produce significant benefits.

PMID- 9193117
TI  - Instrument development: the Mental Health-Related Self-Care Agency Scale.
AB  - This article addresses the development and initial testing of an instrument to
      measure individual's capabilities to perform mental health related self-care. A
      two-step process of development and judgment (Lynn, 1986) was used to develop and
      evaluate this instrument's content validity. The development phase included
      explication of the content domains, item generation, and instrument formation.
      Evaluation of the content validity was addressed by an expert panel for
      theoretical and clinical relevance. These processes resulted in a 35 item, self
      report questionnaire. A pilot study supported the Mental Health Self-Care Agency
      Scale as a reliable and valid instrument appropriate for theory-testing research.

PMID- 9193118
TI  - Single subject experimentation for psychiatric nursing.
AB  - Mental health nurses encounter countless opportunities to assess medication and
      intervention efficacy but often find themselves relying solely on descriptive
      case study accounts and familiar group comparison methodology. Although case
      studies are useful, they lack scientific rigor and group comparison designs may
      not be suited to certain client populations or research questions that address
      individual client characteristics. The purpose of this article is to describe
      single subject experimentation, contrast this approach with case study and group
      comparison designs, and discuss how this type of scientific inquiry can be
      incorporated in psychiatric nursing practice.

PMID- 9193119
TI  - Characteristics of long-term psychiatric patients hospitalized in Tokyo, Japan.
AB  - This study examined the records of all psychiatric patients hospitalized over 1
      year who were committed as a result of a penal code violation at a public sector
      hospital located in Tokyo, Japan. The 30 patients were all men, Japanese, and
      primarily unmarried. Affective and organic disorders were totally absent. None of
      the new antipsychotic medications were used. There was no relationship between
      nursing diagnosis and Diagnostic and Statistical Manual of Mental Disorders-IV
      (DSM-IV) diagnosis. The demands for health care reform are beginning in Japan.
      Managing the integration of the long-term psychiatric patient into the community
      is one of the main challenges identified in this study.

PMID- 9193120
TI  - The relationship of vocally disruptive behavior and previous personality in
      severely demented institutionalized patients.
AB  - The aim of this study was to explore the previous personalities of patients,
      their behavior during the course of the disease, and the relationship between the
      previous personality and vocally disruptive behavior of severely demented
      patients. Twenty-one severely demented patients identified as vocally disruptive
      and 19 severely demented control subjects who were matched for gender and ward
      were studied. A family member or close relative who knew the patient very well
      described the patient's personal characteristics from what they judged to be the
      "best" period in the patient's life and responded, on behalf of the patient, to
      the 57 items in a modified version of the Eysenck Personality Inventory. The
      results of this study can be interpreted to indicate that a previous personality
      described as introverted, rigid, and with a tendency to control emotions, as
      remembered retrospectively by a close family member, may correlate to current
      disruptive behavior. Despite the limitations of this study, the findings
      indicated that a patient's previous personality characteristics need to be taken
      into consideration because they may partially explain vocal activity and are
      therefore important for the provision of nursing care. Further research has to be
      performed to highlight the impact of previous personality characteristics on
      various kinds of behavior during the course of the disease.

PMID- 9193121
TI  - The lived experience of power and powerlessness in psychiatric nursing: a
      Heideggerian hermeneutical analysis.
AB  - The purpose of this study was to discover some of the meanings inherent in
      psychiatric nursing practice. The specific question was, "What is the meaning of
      power and powerlessness as it occurs in the lived experience of practicing
      psychiatric nurses." The therapeutic nurse-patient relationship is a primary
      concern for psychiatric nursing. Therefore, issues of power and powerlessness
      become salient as they affect clients in the mental health system and the
      clinicians who work with them. If power and powerlessness are important aspects
      in a conceptualization of mental illness and its treatment, then they will affect
      clinicians and the relationships that they have with their clients. This study
      focused on the lived experience of 10 psychiatric registered nurses.
      Semistructured interviews with these nurses were audiotaped and transcribed into
      text. They were then analyzed hermeneutically using the philosophical grounding
      of Heideggerian phenomenology and the hermeneutical methods that are based on
      that philosophy. One constitutive pattern revealed was "The Power of Knowing."
      Three relational themes were "Power as Connectedness in Relationships," "Being
      Tested by Fire," and "Power as Having a Voice." The results of this study enable
      nurses to understand their practice better and lead to strategies for empowerment
      of both nurses and the people that they care for. In addition, the use of a
      hermeneutical data analysis approach has further shown the relevance of this
      method for knowledge generation in psychiatric nursing.

PMID- 9193122
TI  - Overlap between dental anxiety and blood-injury fears: psychological
      characteristics and response to dental treatment.
AB  - The relationship between dental anxiety and blood/body injury (BI) fears was
      examined in a sample of 1420 adults. Based on their responses to two mail
      questionnaires, they were classified into one of four groups: Group 1--neither
      dentally anxious nor BI fearful; Group 2--BI fearful only; Group 3--dentally
      anxious only; Group 4--both dentally anxious and BI fearful. Overall, only 16% of
      dentally anxious subjects were BI fearful while 31.6% of those with high levels
      of BI fears were dentally anxious. While subjects in Group 2 were more fearful of
      dentistry than those in Group 1, they were substantially less so than subjects in
      Groups 3 and 4. Moreover, even BI stimuli in the dental setting evoked lower
      levels of anxiety for subjects in Group 2 compared to Group 3 and 4. However,
      rates of fainting or near fainting experiences in the dental situation were
      similar for all three groups. Group 3 and 4 were similar in terms of fear evoking
      stimuli and patterns of anxiety response. Subjects in Group 4 had more
      agoraphobic symptoms and social interaction fears and had higher scores on the
      Anxiety Sensitivity Index and Speilberger Trait Anxiety Index. This suggests that
      Group 4 is comprised of individuals who are more likely to be multiphobic and
      exhibit generalized anxiety states. Although BI fears are a significant component
      of dental anxiety, their overall contribution is relatively small.

PMID- 9193124
TI  - Manipulation of dangerousness judgements to fear-relevant stimuli: effects on a
      priori UCS expectancy and a posteriori covariation assessment.
AB  - Using a covariation assessment procedure, the present study pre-experimentally
      manipulated subjects' assessments of the dangerousness of fear-relevant stimuli.
      The results demonstrated that this manipulation subsequently influenced both a
      priori expectancy that the stimulus will be followed by an aversive consequence
      (UCS), and inflated an a posteriori covariation bias indicating that subjects
      judged the stimulus to be followed more frequently by the aversive UCS than by a
      non-aversive stimulus. These findings support the view that judgments about such
      characteristics as the dangerousness of a stimulus causally contribute to a UCS
      expectancy bias and an a posteriori covariation bias, and thus contribute to the
      formation of selective associations.

PMID- 9193123
TI  - Cued UCS rehearsal and the impact of painful conditioned stimuli: UCS rehearsal
      increases SCRs but reduces experienced pain.
AB  - The effects of cued UCS rehearsal on responses to a mildly painful CS previously
      paired with a highly painful UCS were investigated. Following CS pretest and CS
      UCS pairings, subjects either mentally rehearsed the UCS (condition 1), received
      the real UCS (condition 2), mentally rehearsed an unrelated painful experience
      (condition 3), or waited (condition 4). In a fifth condition, subjects received
      CS and UCS unpaired before engaging in UCS rehearsal. During a posttest, subjects
      received CS-alone presentations and rated experienced pain and anxiety, while
      electrodermal responses were assessed. These responses were compared to pretest
      and acquisition responses. UCS rehearsal led to pain reduction of the CS
      comparable to the habituation effect of real UCS confrontation. In line with an
      associative basis for this effect, UCS rehearsal did not influence the pain
      experience of an unpaired CS. Yet, rehearsal of a memory of an unrelated painful
      experience also reduced the pain experience of the CS. Electrodermal responses
      showed delayed extinction and incubation after UCS rehearsal, but there were no
      significant effects on subjective anxiety. Incubation of electrodermal responses
      was related to low self-consciousness and the combination of low self
      consciousness and high trait anxiety. Trait anxiety and worry proneness per se
      did not relate to incubation. The findings suggest that worry-like processes can
      have functional values like reducing pain impact, and cast doubt upon the
      contention that UCS rehearsal leads to an overall incubation of fear.

PMID- 9193125
TI  - Bias in interpretation of ambiguous scenarios in eating disorders.
AB  - Eating disorders appear to be associated with biased information processing,
      particularly in judgments involving the self. This study investigated three
      possible biases. Patients with anorexia nervosa, patients with bulimia nervosa
      and female controls completed questionnaires designed to assess interpretation of
      ambiguous scenarios with either a negative or positive outcome. When events had a
      negative outcome the patients responded spontaneously to open-ended questions
      with a weight and shape interpretation. Later, in a forced-choice format, they
      selected the weight and shape interpretation in preference to interpretations not
      connected to weight and shape. In both open-ended and forced-choice format this
      bias was specific to judgments involving the self. When events had a positive
      outcome the bias was reversed and, in the two formats, it was found only in
      judgments involving others. In both cases, i.e. for negative self-referent events
      and for positive other-referent events, patients predicted that weight and shape
      explanations were more likely. Both groups of patients estimated that negative
      outcomes involving the self would be more costly. The patients with bulimia
      nervosa also estimated that positive outcomes involving the self would be more
      beneficial. Theoretical explanations and clinical implications are discussed.

PMID- 9193126
TI  - Self-directed treatment with minimal therapist contact: preliminary findings for
      obsessive-compulsive disorder.
AB  - The efficacy of a brief intervention for obsessive-compulsive disorder (OCD) was
      examined with nine clients. Treatment consisted of five meetings with the
      therapists, readings from When once is not enough (Steketee & White, 1990), and
      self-directed exposure with response prevention. The self-report version of the
      Yale-Brown Obsessive-Compulsive Scale was the primary dependent measure.
      Participants who received treatment after a 6-week delay showed stability of
      severity of OCD over the waiting period. As a group, participants showed
      statistically significant improvement on the main outcome measures. One-third of
      the clients met criteria for clinically significant improvement indicating that
      some individuals suffering with OCD can be helped with a brief intervention.

PMID- 9193127
TI  - Diagnosing DSM-IV--Part I: DSM-IV and the concept of disorder.
AB  - In this first article in a two-article series, I diagnose' a problem with DSM-IV,
      specifically, the overinclusiveness of its diagnostic criteria. Using the harmful
      dysfunction analysis of the concept of disorder (Wakefield, 1992a, American
      Psychologist, 47, 373-388) as a framework, I argue that DSM-IV criteria for many
      diagnostic categories fail to satisfy the analysis' dysfunction' requirement,
      that is, the criteria do not distinguish harmful conditions due to internal
      dysfunctions from harmful conditions that are nondisordered 'problems in living'.
      The overinclusiveness problem, I suggest, can be partly dealt with by giving up
      purely symptomatic criteria and contextualizing diagnosis to take into account
      the relationship between triggering causes and resulting symptoms. In Part II
      (Wakefield, 1997, Behaviour Research and Therapy, 35, 651-665, I examine
      Eysenck's (1986, Contemporary directions in psychopathology: Toward the DSM-IV)
      proposal for a dimensional diagnostic system to supplant DSM-IV.

PMID- 9193128
TI  - Diagnosing DSM-IV--Part II: Eysenck (1986) and the essentialist fallacy.
AB  - In Part I (Wakefield, 1997, Behaviour Research and Therapy, 35, 633-649) of this
      two-article series, I used the harmful dysfunction analysis of the concept of
      disorder (Wakefield, 1992a, American Psychologist, 47, 373-388) to 'diagnose' a
      problem with DSM-IV. I argued that DSM-IV diagnostic criteria often violate the
      'dysfunction' requirement by invalidity classifying harms not caused by
      dysfunctions as disorders. In Part II, I examine Eysenck's (Eysenck, 1986,
      Contemporary directions in psychopathology: Toward the DSM-IV) argument that DSM
      commits a 'categorical fallacy' and should be replaced by dimensional diagnoses
      based on Eysenckian personality traits. I argue that Eysenck's proposed
      diagnostic criteria violate the 'harm' requirement by invalidly classifying
      symptomless conditions as disorders. Eysenck commits an 'essentialist fallacy';
      he misconstrues 'disorder' as an essentialist theoretical concept when in fact it
      is a hybrid theoretical-practical or 'cause-effect' concept. He thus ignores the
      harmful effects essential to disorder that are captured in DSM's symptom-based
      categories.

PMID- 9193129
TI  - Cognitive assessment of obsessive-compulsive disorder. Obsessive Compulsive
      Cognitions Working Group.
AB  - Recent theories of obsessive-compulsive disorder (OCD) emphasize the importance
      of cognitive contents (beliefs and appraisals) and cognitive processes in the
      etiology and maintenance of OCD. In order to evaluate these theories and to
      assess the mechanisms of treatment-related change, it is necessary to develop
      measures of the relevant cognitive contents and processes. Several scales have
      been developed, although many are unpublished and there is a great deal of
      overlap among measures. The purpose of the present article is to describe the
      progress of an international group of investigators who have commenced a
      coordinated effort to develop a standardized set of cognitive measures. This
      article describes the theoretical bases and clinical importance of such an
      endeavor, and the proceedings of the working group meetings are summarized.
      Several methods of assessment are reviewed, including idiographic methods,
      information processing paradigms, and self-report measures. The working group is
      currently developing and evaluating self-report measures of appraisals about
      intrusions, and self-report measures of OC-related beliefs. Consensus ratings
      indicated that 6 belief domains are likely to be important in OCD. These are
      beliefs pertaining to: (1) inflated responsibility; (2) overimportance of
      thoughts; (3) excessive concern about the importance of controlling one's
      thoughts; (4) overestimation of threat; (5) intolerance of uncertainty; and (6)
      perfectionism.

PMID- 9193130
TI  - A new class of pyrrolidin-2-ones: synthesis and pharmacological study.

PMID- 9193131
TI  - From molecular recognition to medicinal chemistry.

PMID- 9193132
TI  - Design and synthesis of novel tyrosine kinase inhibitors using a pharmacophore
      model of the ATP-binding site of the EGF-R.
AB  - One of the most promising targets for the rational design of anti-cancer drugs is
      the family of the EGF-receptor protein tyrosine kinases. Despite the high
      sequence homology within the ATP-binding region of protein tyrosine and/or serine
      threonine kinases, ATP-competitive compounds have the potential to be selective
      inhibitors of protein kinases. Dianilino-phthalimides CGP 52 411 and CGP 53,353
      have been identified as potent and ATP-competitive inhibitors of the EGF-R
      tyrosine kinase with no or only minor activity against a panel of tyrosine and
      serine/threonine kinases. Using a calculated 3-D computer model of the catalytic
      domain of the EGF-R-tyrosine kinase together with CGP 52 411 as example of an ATP
      competitive inhibitor, a pharmacophore model for ATP-competitive inhibitors in
      the active site of the EGF-R PTK was developed. With the help of this model, 4
      phenylamino-7H-pyrrolo[2,3-d]pyrimidines were then identified as new potent EGF-R
      PTK inhibitors. In an interactive process, the class of the 4-phenylamino-pyrrolo
      pyrimidines was optimized and structure-activity-relationship of a series of
      derivatives thereof are discussed. In vitro, the most active compounds (CGP 59
      326, CGP 60 261, CGP 62 706) inhibited the EGF-R tyrosine kinase with IC50 value
      between 6-30 nM. High selectivity towards a panel of non-receptor tyrosine
      kinases (c-SRC, v-Abl) and serine/threonine kinases (PKC alpha, PKA) was
      observed. Kinetic analysis revealed competitive type kinetics relative to ATP. In
      cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by these
      compounds at IC50 values between 0.1-0.3 microM, whereas the ligand-induced
      receptor autophosphorylation of the PDGR-R was not effected by concentrations up
      to 100 microM. Furthermore, CGP 59 326, CGP 60 261, CGP 62 706 were able to
      selectively inhibit c-fos mRNA expression in EGF-dependent cell lines with (IC50)
      approx. 0.1-1 microM) but not in EGF-independent cell systems (IC50 > 100
      microM). Proliferation of the EGF-dependent MK cell line was inhibited with
      similar IC50 values. In addition, CGP 59 326 and CGP 62 706 showed good in vivo
      efficacy at low doses after oral or subcutaneous administration in nude mice
      tumor models using xenografts of the EGF-dependent A431 cell lines. The ED50
      values were between 1.5-2 mg/kg. Phenylamino-pyrrolo-pyrimidines therefore
      represent a new series of tyrosine kinase inhibitors which preferentially inhibit
      the EGF-mediated signal transduction pathway and have the characteristics for
      further evaluation as anticancer agents.

PMID- 9193133
TI  - Computer modelling of G protein-coupled receptors: promises and drawbacks.

PMID- 9193134
TI  - Results of blood lead screening in children referred for behavioral disorders.
AB  - This study reviews findings from blood lead level screening in children referred
      to an Attention Deficit Hyperactivity Disorder clinic. Results obtained from 102
      children revealed a sample mean blood lead level of 2.29 micrograms/dL and one
      patient with a mildly elevated blood lead level. Comparing these findings to
      results of national studies suggests that these children are not at higher risk
      for elevated lead levels than is the average child living in a similar setting.

PMID- 9193135
TI  - Functional cloning of candidate genes that regulate Purkinje cell-specific gene
      expression.

PMID- 9193136
TI  - Transverse and longitudinal patterns in the mammalian cerebellum.

PMID- 9193137
TI  - An anatomical model of cerebellar modules.

PMID- 9193138
TI  - The distribution of corticotropin-releasing factor (CRF), CRF binding sites and
      CRF1 receptor mRNA in the mouse cerebellum.
AB  - The purpose of the present study is to determine the distribution of CRF
      containing afferents, and correlate these findings with the distribution of CRF
      binding sites and the neuronal localization of mRNA for the CRF1 receptor in the
      cerebellum of a single species, the mouse. Corticotropin releasing factor (CRF)
      has been localized within climbing fibers and mossy fibers throughout the
      cerebellar cortex of the mouse using immunohistochemistry. CRF immunoreactive,
      axonal varicosities also are present within all four of the cerebellar nuclei.
      125I-labeled CRF binding sites are evident throughout all three layers of the
      cerebellar cortex (molecular, Purkinje and granule cell layers), but are not seen
      within the cerebellar nuclei. In situ hybridization histochemistry was employed
      using an antisense riboprobe corresponding to the full length sequence of the rat
      mRNA for the CRF1 receptor. Positive signal is present throughout the cerebellum
      in Purkinje cells and the granule cell layer. CRF1 receptor mRNA also is
      expressed within all four of the cerebellar nuclei. Further experiments are
      required to reconcile the lack of CRF binding sites in the cerebellar nuclei with
      the positive mRNA receptor expression and the presence of immunoreactive axonal
      varicosities. In previous physiological experiments, iontophoretic application of
      CRF enhances spontaneous as well as quisqualate-induced activity of Purkinje
      cells in slice preparations of the mouse cerebellum. When the results of the
      anatomical techniques are compared to the physiological data, there is convergent
      evidence to suggest that CRF influences the firing rate or responsiveness of
      Purkinje cells directly via release of the peptide from the climbing fiber system
      and indirectly via the mossy fiber-granule cell-parallel fiber circuit. Taken
      together, these anatomical and physiological data provide strong evidence to
      suggest that, in the adult cerebellum, CRF functions as a neuromodulator.

PMID- 9193139
TI  - Cholinergic innervation and receptors in the cerebellum.
AB  - We have studied the source and ultrastructural characteristics of ChAT
      immunoreactive fibers in the cerebellum of the rat, and the distribution of
      muscarinic and nicotinic receptors in the cerebellum of the rat, rabbit, cat and
      monkey, in order to define which of the cerebellar afferents may use ACh as a
      neurotransmitter, what target structures are they, and which cholinergic receptor
      mediate the actions of these pathways. Our data confirm and extend previous
      observations that cholinergic markers occur at relatively low density in the
      cerebellum and show not only interspecies variability, but also heterogeneity
      between cerebellar lobules in the same species. As previously demonstrated by
      Barmack et al. (1992a,b), the predominant fiber system in the cerebellum that
      might use ACh as a transmitter or a co-transmitter is formed by mossy fibers
      originating in the vestibular nuclei and innervating the nodulus and ventral
      uvula. Our results show that these fibers innervate both granule cells and
      unipolar brush cells, and that the presumed cholinergic action of these fibers
      most likely is mediated by nicotinic receptors. In addition to cholinergic mossy
      fibers, the rat cerebellum is innervated by beaded ChAT-immunoreactive fibers. We
      have demonstrated that these fibers originate in the pedunculopontine tegmental
      nucleus (PPTg), the lateral paragigantocellular nucleus (LPGi), and to a lesser
      extent in various raphe nuclei. In both the cerebellar cortex and the cerebellar
      nuclei these fibers make asymmetric synaptic junctions with small and medium
      sized dendritic profiles. Both muscarinic and nicotinic receptor could mediate
      the action of these diffuse beaded fibers. In the cerebellar nuclei the beaded
      cholinergic fibers form a moderately dense network, and could in principle have a
      significant effect on neuronal activity. For instance, the cholinergic fibers
      arising in the PPTg may modulate the excitability of the cerebellonuclear neurons
      in relation to sleep and arousal (e.g. McCormick, 1989). Studies on the
      distribution of cholinergic markers in the cerebellum have proven valuable
      besides the issue whether cholinergic mechanism play a role in the cerebellar
      circuitry, because they illustrate a complexity of the cerebellar anatomy that
      extends beyond its regular trilaminar and foliar arrangement. For instance, AChE
      histochemistry has been shown to preferentially stain the borders of white matter
      compartments (the 'raphes', Voogd, 1967), and therefore is useful in
      topographical analysis of the cortico-nuclear and olivocerebellar projections
      (Hess and Voogd, 1986; Tan et al., 1995; Voogd et al., 1996; see Voogd and
      Ruigrok, 1997, this Volume). ChAT-immunoreactivity, at least in rat, appears to
      be a good marker to outline the morphological heterogeneity of mossy fibers, and
      m2-immunocytochemistry could be used to label (subpopulations of) Golgi cells,
      subsets of mossy fibers and, in the rabbit, a specific subset of Purkinje cells
      (Jaarsma et al., 1995).

PMID- 9193140
TI  - Molecular organization of cerebellar glutamate synapses.
AB  - The organization of key molecules at glutamatergic synapses in the rat cerebellar
      cortex as analyzed by high resolution immunocytochemical techniques using gold
      particles as markers. The distinct compartmentation of glutamate and glutamine
      was consistent with biochemical data indicating an active role of glia in the
      removal of released glutamate and in the supply of glutamine for de novo
      synthesis of transmitter glutamate. The presence in glial cells of two different
      glutamate transporters, GLT1 and GLAST, provided further support of this concept.
      Both transporters were selectively expressed in glial membranes and occurred at
      higher densities in glial processes surrounding parallel fiber synapses with
      spines than in glial processes associated with parallel fiber synapses with
      dendritic shafts. At the former type of synapse, gold particles signalling GLT1
      and GLAST could be found within a few nanometers of the postsynaptic density. The
      rat cerebellum also contains a homologue (rEAAC1) of the glutamate transporter
      EAAC1, originally cloned from rabbit, mRNA encoding this transporter was
      restricted to neurons. The exact localization of the rEAAC1 transporter molecules
      at cerebellar synapses remains to be determined but immunocytochemical and
      physiological data from other laboratories suggest that they may be
      preferentially expressed in postsynaptic membranes. Gold particles representing
      immunoreactivity for the AMPA receptor subunits GluR2/3 were found along the
      entire mediolateral extent of the postsynaptic specialization of parallel fiber
      synapses and were rarely encountered at non-synaptic membranes. The present data
      show that molecules engaged in signalling at cerebellar glutamatergic synapses
      are precisely organized, consistent with the requirements for rapid signal
      transmission and efficient removal and recycling of transmitter.

PMID- 9193141
TI  - Compartmentalised distribution of GABAA and glutamate receptors in relation to
      transmitter release sites on the surface of cerebellar neurones.

PMID- 9193142
TI  - The unipolar brush cells of the mammalian cerebellum and cochlear nucleus:
      cytology and microcircuitry.
AB  - The unipolar brush cell (UBC) is a novel type of small neuron that is
      characterized by sets of morphological and chemical phenotypes. UBCs occur in the
      granular layer of the mammalian cerebellar cortex, particularly in folia of the
      vestibulocerebellum, and in the granule cell domains of the dorsal cochlear
      nucleus. The UBC is characterized by a single dendrite that terminates with a
      brush-like tip of dendrioles. The soma, the dendritic stem, and especially the
      dendrioles emit short, non-synaptic appendages. The dendrioles represent the main
      synaptic apparatus of the UBC and articulate tightly with a single mossy fiber
      rosette forming a glomerular array characterized by an extraordinarily extensive
      synaptic contact. Electron microscopic and electrophysiological observations
      indicate that the unusual synaptic ultrastructure may produce entrapment of
      neurotransmitter in the synaptic cleft. While ionotropic glutamate receptors are
      enriched in correspondence of the postsynaptic density, metabotropic glutamate
      receptors are situated extrasynaptically and are particularly enriched at the
      appendages, which usually do not bear synaptic junctions. Some of the UBCs
      receive their input from choline acetyltransferase-positive mossy rosettes
      originating from the vestibular nuclei, suggesting that ACh and glutamate are co
      released at these synapses. The UBC brush occupies a glomerulus where granule
      cell dendrites are intermixed with the UBC dendrioles, both of which receive
      synapses from the same mossy fiber rosette and portions of the Golgi axonal
      plexus. In addition, the dendrioles are presynaptic to granule cell dendrites,
      forming dendrodendritic contacts that display features of excitatory synapses.
      Branches of the UBC axon in the granular layer bear large endings resembling
      mossy fibers. The UBCs may represent an extraordinary device for feedforward,
      excitatory links along the mossy fiber pathways of cerebellum and dorsal cochlear
      nucleus.

PMID- 9193143
TI  - Physiology of transmission at a giant glutamatergic synapse in cerebellum.

PMID- 9193144
TI  - Cerebellar nuclei: the olivary connection.
AB  - This chapter gives an overview of the relation between the inferior olive and the
      cerebellar nuclei based on tracing and electrophysiological experiments in rats
      and cats. The olivary and cerebellar nuclear masses appear to maintain a precise
      topographical relationship. The olivary projection to the cerebellar nuclei is
      strictly contralateral, originates as climbing fiber collaterals, and is
      excitatory. The cerebellar projection to the inferior olive is exactly reciprocal
      to the olivonuclear projection, but, in addition, also has a variable but
      definite ipsilateral component, and has been demonstrated to be GABAergic.
      Stimulation and lesion experiments carried out in cat imply that the cerebellar
      nucleo-olivary pathway may be involved in regulating the oscillatory capabilities
      of olivary cells and as such may also have an effect on the synchrony of olivary
      firing. Subsequent stimulation experiments performed in rats suggests that
      synchronous firing of olivary neurons may result in profound effects in
      cerebellar nuclear neurons.

PMID- 9193145
TI  - Functional significance of excitatory projections from the precerebellar nuclei
      to interpositus and dentate nucleus neurons for mediating motor, premotor and
      parietal cortical inputs.

PMID- 9193146
TI  - The physiological effects of serotonin on spontaneous and amino acid-induced
      activation of cerebellar nuclear cells: an in vivo study in the cat.
AB  - It is well established that cerebellar efferents originate from neurons located
      within the cerebellar nuclei. Neurons within these nuclei receive excitatory
      inputs derived from the axons that arise from cells in several different regions
      of the brainstem and spinal cord, some of which continue on to terminate as mossy
      fibers and climbing fibers in the cerebellar cortex. GABA-induced inhibition in
      the nuclei is derived primarily from Purkinje cells located in the overlying
      cortex and possibly from axonal collaterals of a population of small, GABAergic
      nuclear neurons. In addition, a third chemically defined system of afferents that
      contain the monoamine serotonin forms a dense plexus of fibers throughout the
      cat's cerebellar nuclei. The intent of this study is to determine the
      physiological effects of serotonin on the spontaneous activity of cerebellar
      nuclear cells as well as that induced by application of the excitatory amino
      acids glutamate and aspartate in an adult in vivo preparation. Iontophoretic
      application of serotonin in anesthetized preparations suppresses both spontaneous
      and excitatory amino acid induced activity. In addition, interactions between
      serotonin and the amino acid analogs quisqualate and NMDA were analyzed; 5HT
      suppresses the excitatory responses of neurons to both analogs. However, there is
      a stronger suppressive effect on quisqualate-induced excitation as compared to
      that elicited by NMDA. In addition to modulating the effects of the excitatory
      amino acids, serotonin also potentiates the inhibitory effects of GABA. However,
      the effect was greatest if the neuron was initially preconditioned with GABA. In
      summary, serotonin acts to suppress amino acid induced activity in cerebellar
      nuclear neurons and to enhance gABA-mediated inhibition. The net effect is a
      decrease in nuclear cell activity and consequently in cerebellar output.

PMID- 9193147
TI  - Salient anatomic features of the cortico-ponto-cerebellar pathway.
AB  - Recent studies of the primate corticopontine projection show that the
      neocerebellum--in addition to connections from motor and sensory areas--receives
      connections from various association areas of the cerebral cortex, some of which
      are thought to be primarily engaged in cognitive tasks. The quantities of such
      connections in relation to those from more clearly motor-related parts of the
      cortex need to be more precisely determined, however. Furthermore, the anatomic
      data on origin of corticopontine fibers needs to be supplemented with
      physiological experiments to clarify their functional properties at the single
      cell level. For example, nothing is known of the functional role of the large
      input from the cingulate gyrus, nor is the input from the posterior parietal
      cortex physiologically characterized. Finally, the scarcity of corticopontine
      connections from the prefrontal cortex in the monkey (and probably also in man)
      may not seem readily compatible with a prominent role of the neocerebellum in
      certain cognitive tasks. We discuss data--in particular from three-dimensional
      reconstructions--indicating that both corticopontine projects and pontocerebellar
      neurons are arranged in a lamellar pattern. Corticopontine and pontocerebellar
      lamellae have similar shapes and orientations but appear to differ in other
      respects. Corticopontine terminal fields are sharply delimited, apparently
      without gradual overlap between projections from different sites in the cortex,
      whereas pontocerebellar lamellae are more fuzzy and exhibit gradual overlap of
      neuronal populations projecting to different targets. In spite of the sharpness
      of the corticopontine projection, there may be many opportunities for convergence
      of inputs from different parts of the cortex. Thus, the wide divergence of
      corticopontine projections produces many sites of overlap, and extensive
      interfaces between different terminal fields enabling convergence of inputs onto
      each neuron. We suggest that the lamellar arrangement of corticopontine terminal
      fields and of pontocerebellar neurons serve to create diversity of
      pontocerebellar neuronal properties. Thus, each small part of the cerebellar
      cortex would receive a specific combination of messages from many different sites
      in the cerebral cortex. The spatial arrangement of cerebrocerebellar connections
      have to be understood both in terms of fairly simple large-scale, gradual
      topographic relationships and an apparently highly complex pattern of divergence
      and convergence. Developmental studies of corticopontine and of pontocerebellar
      projections together with three-dimensional reconstructions in adults suggest
      that the highly complex adult connectional pattern may be created by simple rules
      operating during development.

PMID- 9193148
TI  - Mossy-fibre sensory input to the cerebellum.
AB  - The role of the spinal and vestibular afferents to the cerebellum in the control
      of movement first began to be recognized towards the end of the 19th century. By
      the middle of the present century it was clear that visual and auditory
      information are also relayed to the cerebellum from the cerebral cortex and
      brainstem by way of the pontine nuclei. Pontine cells project to the cerebellar
      cortex where they terminate as mossy fibres. The corticopontine projection arises
      from cells in lamina V of the cerebral cortex. Cells in the rat primary
      somatosensory cortex also provide an input to the basal ganglia, but the two
      populations are largely segregated in distinct sub-laminae. In monkeys, and
      probably in humans, the cortical visual input to the pontine nuclei arises from
      the dorsal stream of extrastriate visual areas. Experimental and clinical
      evidence suggest that damage to this pathway at the cortical level, or
      interruption of its corticopontine fibres within the internal capsule produce
      profound disturbance in visuomotor guidance. One of the major pathways through
      the brain for the visual guidance of movement is relayed from the dorsal stream
      of extrastriate areas to the cerebellum by way of the pontine nuclei.

PMID- 9193149
TI  - Reciprocal trophic interactions between climbing fibres and Purkinje cells in the
      rat cerebellum.
AB  - In the adult cerebellum both the climbing fibre arbour and the Purkinje cell are
      very plastic and each element is able to exert a remarkable action on the other
      one. The adult phenotype of the Purkinje cell is strictly dependent on the
      presence of its climbing fibre arbour. When the climbing fibre is missing, the
      Purkinje cell undergoes a hyperspiny transformation and becomes hyperinnervated
      by the parallel fibres. However, this change is fully reversible. The climbing
      fibre-deprived Purkinje cell is able to elicit sprouting of nearby located intact
      climbing fibres and the new arbour is able to fully restore synaptic connections
      which appear normal both morphologically and functionally. Multiple climbing
      fibre innervation of a single Purkinje cell persists in the adult hypogranular
      cerebellum. The different fibres are distributed to separate dendritic regions,
      suggesting a local competition between the different arbours for their territory.
      It is postulated that in the intact rat, an activity dependent mechanism of the
      parallel fibre favours the predominance of one arbour with the elimination of its
      competitors. When the Purkinje cell is deleted, the climbing fibre arbour becomes
      heavily atrophic and reduced in size. The analysis of the pattern of this atrophy
      indicates that the climbing fibre arbour is made by two compartments: a proximal
      one, whose survival depends on the integrity of the inferior olive, and a distal
      one, which represents the true pre-synaptic site, which strictly depends on the
      target. The climbing fibre terminal arbour is able to extend its territory of
      innervation not only when adult intact climbing fibres are confronted with nearby
      denervated Purkinje cells, but also when an embryonic cerebellum is grafted onto
      the surface of an adult unlesioned cerebellum. In this case, collaterals of
      intact climbing fibre arbours elongate through the pial surface, enter the graft
      to innervate the Purkinje cells. This growth is likely under the influence of a
      tropic signal released by the embryonic Purkinje cells. This suggests that the
      sprouting observed in the adult rat following a subtotal inferior olive lesion is
      also triggered by a similar factor. The axonal elongation and the consequent
      synaptogenesis are likely guided by local cues. In this condition, the
      distribution of the new collateral reinnervation occurs within its projectional
      map. In addition, when the inferior cerebellar peduncle is sectioned at birth,
      the climbing fibres of the non-deafferented hemicerebellum emit collaterals which
      cross the midline and innervate cerebellar strips which are symmetrically
      positioned relative to the intact side. In the grafting experiments, both the
      migrated and non-migrated Purkinje cells show the typical electrophysiological
      properties of the mature cerebellum. These data show that the disappearance of
      neuronal elements is not a necessary prerequisite to allow new neurones to become
      fully morphologically and functionally integrated into an adult brain. The
      reciprocal trophic influence between the climbing fibres and the Purkinje cells
      shown in the present series of experiments are likely operative in the adult
      brain not only in pathological conditions and they could give a basic
      contribution to the synaptic plasticity underlying learned behaviour.

PMID- 9193150
TI  - Intrinsic properties and environmental factors in the regeneration of adult
      cerebellar axons.
AB  - The success of axon regeneration in the adult mammalian brain depends on the
      presence of growth-permissive environmental conditions as well as on specific
      properties of the affected neurons. To investigate the relative contribution of
      extrinsic cues and intrinsic determinants to reparative processes we have
      investigated the regenerative properties of olivocerebellar and Purkinje cell
      axons. When these axon populations are severed in the cerebellar white matter and
      confronted with embryonic neural grafts of cerebellar or extracerebellar origin,
      the former vigorously regenerate into the transplant, whereas the latter
      invariably fail to do so (Rossi et al., 1995). The same response occurs when
      dissociated Schwann cells are implanted in the lesion site: Purkinje cell axons
      fail to regrow, whereas olivocerebellar fibres regenerate for considerable
      distances. Within the graft, regenerating fibres follow tortuous courses along
      Schwann cell bundles and sometimes end with poorly developed terminal plexuses.
      Some of them, however, succeed in crossing the graft and grow further into the
      host cortex, where they break into fine terminal branches confined to the
      granular layer. The remarkable regenerative response of olivocerebellar axons
      revealed by these experiments might be an intrinsic reaction of the affected
      neurons to axon injury or it might be elicited by growth promoting cues derived
      from the grafts. To elucidate this point we have undertaken the investigation of
      cellular changes occurring in adult inferior olivary neurons following the
      transection of the inferior cerebellar peduncle. Our results show that axotomy
      induces a series of cellular changes, or reparative and regressive character,
      which ultimately lead to cell death. Interestingly, however, these modifications
      are not uniformly distributed throughout the whole inferior olive. (i) Neuronal
      atrophy and degeneration progress more rapidly in the PO and DAO than in the MAO.
      (ii) A subpopulation of inferior olivary neurons become reactive for NADPH
      diaphorase histochemistry, and their preferential localisation in the MAO
      suggests that this modification is related to the longer survival of these cells
      after axotomy. (iii) The developmentally regulated calcitonin gene-related
      peptide (CGRP) is reexpressed by a subset of neurons in the caudal nuclear
      compartments. These results further emphasise the conclusion that the dissimilar
      regenerative response of Purkinje cell and olivocerebellar axons confronted with
      permissive environmental conditions is due to different intrinsic properties of
      these neuronal populations. The reexpression of developmentally regulated
      substances by axotomised inferior olivary neurons suggests that their reparative
      reaction is triggered by axon injury. However, the pattern of growth of
      regenerating olivocerebellar axons is strongly conditioned by environmental
      constraints, which, in the present experimental conditions, do not allow them to
      reattain denervated Purkinje cells.

PMID- 9193151
TI  - Signal processing in the C2 module of the flocculus and its role in head movement
      control.
AB  - The major novel findings described and reviewed in the present study have all
      been demonstrated in the C2 module, which is formed by the rostral medial
      accessory olive, posterior interposed nucleus of the cerebellum, and zone C2. We
      show (1) that expression of dendritic lamellar bodies and dendrodendritic gap
      junctions in the rostral medial accessory olive are both down regulated by
      removal of the GABAergic input from the posterior interposed nucleus of the
      cerebellum to electrotonically coupled olivary dendrites; (2) that the high
      density of dendritic lamellar bodies in the rostral medial accessory olive can be
      correlated with a relatively high level of CS synchrony in the C2 zone of the
      flocculus; and (3) that the C2 zone of the flocculus is involved in head
      movements and probably gaze control. These results support the hypothesis that
      dendritic lamellar bodies are associated with dendrodentritic gap junctions, and
      they suggest that appropriate executions of compensatory head and eye movements
      require particular levels of complex spike synchrony in the flocculus.

PMID- 9193152
TI  - Control of the three-dimensional dynamic characteristics of the angular vestibulo
      ocular reflex by the nodulus and uvula.

PMID- 9193153
TI  - Cholinergic control in the floccular cerebellum of the rabbit.

PMID- 9193154
TI  - Behavioural analysis of Purkinje cell output from the horizontal zone of the cat
      flocculus.

PMID- 9193155
TI  - Characterization of Purkinje cells in the goldfish cerebellum during eye movement
      and adaptive modification of the vestibulo-ocular reflex.
AB  - The discharge characteristics of Purkinje cells were analyzed in the goldfish
      cerebellum during eye movement and adaptation of the vestibulo-ocular reflex
      (VOR). Purkinje cells, identified by the simultaneous recording of complex and
      simple spikes, were recorded in the cerebellar area where electrical
      microstimulation elicited ipsiversive horizontal eye movements. Simple spikes of
      Purkinje cells displayed signals related to head and/or eye velocity as
      determined independently during either VOR suppression or optokinetic
      stimulation, respectively. Head velocity-only Purkinje cells (12%) increased
      their firing rate in relationship to ipsilateral head movements. Two types of eye
      velocity-only Purkinje cells (28%) were found that responded either in phase with
      ipsi- (16%) or contralateral (12%) eye movement, respectively. Purkinje cells
      combining both eye and head velocity (60%) were classified into two groups
      according to their preferred direction for eye movement. Eye velocity signals
      either added to (18%) or subtracted from (42%) head velocity during all visuo
      vestibular interactions. Short term adaptive changes of the VOR were induced by
      oscillating goldfish in a moving visual surround that modified the ratio of eye
      to head velocity (gain) from a level of 1.0 (16 degrees/s) towards gains ranging
      from 2.5 (40 degrees/s) to -1.0 (-16 degrees/s). Simple spike modulation of
      individual Purkinje cells was shown to correlate well with VOR performance
      throughout adaptation irrespective of training direction. Purkinje cell behavior
      always equaled the algebraic summation of eye and head velocity signal
      sensitivity. Causality of signal generation was addressed by measuring Purkinje
      cell responses to both eye and head velocity separately throughout the time
      course of VOR adaptation. The sensitivity of each type of Purkinje cell was found
      to be independent of the VOR gain state. We therefore conclude that the changes
      responsible for short term VOR plasticity do not occur in the cerebellum. These
      observations suggest that Purkinje cells integrate corollary head and eye
      velocity signals to continuously adjust the set point of brainstem VOR
      interneurons that embrace the substantive site for adaptive plasticity.

PMID- 9193156
TI  - Role of the Y-group of the vestibular nuclei and flocculus of the cerebellum in
      motor learning of the vertical vestibulo-ocular reflex.

PMID- 9193157
TI  - Aspects of cerebellar function in relation to locomotor movements.

PMID- 9193158
TI  - The control of forelimb movements by intermediate cerebellum.
AB  - In a series of studies, the functional organization of cerebellar regions
      contributing to the control of forelimb movements via the rubro- and
      corticospinal tracts has been characterized in the cat. The system consists of
      the cerebellar cortical C1, C3 and Y zones and their efferent intracerebellar
      nucleus, the interpositus anterior. Based on analyses of cutaneous and muscle
      afferent climbing fibre input, of corticonuclear connections and of limb
      movements controlled, a modular organization of this cerebellar control system is
      proposed. Each module consists of a number of cortical microzones, defined by
      their homogeneous climbing fibre input, and a group of neurones in nucleus
      interpositus anterior on which these microzones converge. The input to climbing
      fibres is multi-modal and originates from cutaneous A beta (tactile), A delta and
      C (nociceptive) fibres and from muscle afferents. The cutaneous receptive fields
      have spatial characteristics suggestive of a relation to elemental movements. For
      most climbing fibres, the spatial relationship between cutaneous and muscle
      afferent input is such that the muscle afferent input originates from muscles
      that, if activated, would tend to move the cutaneous receptive field of the
      climbing fibre towards a stimulus applied to the skin. By contrast, the limb
      movement controlled by the module often has the opposite direction, and would
      thus tend to move the cutaneous receptive field away from a stimulus applied to
      the skin. Functional implications of this organization for the involvement of
      these regions in acute and adaptive motor control of limb movements are
      discussed.

PMID- 9193159
TI  - What features of visually guided arm movements are encoded in the simple spike
      discharge of cerebellar Purkinje cells?

PMID- 9193160
TI  - Some organizing principles for the control of movement based on olivocerebellar
      physiology.
AB  - Motor control is defined as the process of restricting the output of the motor
      nervous system so that meaningful and coordinated behavior ensues. The high
      dimensionality of the computation underlying motor control is presented and a
      simplifying framework is outlined. Evidence that movements are performed non
      continuously is reviewed as is the construct of the 'motor synergy' as a
      fundamental unit of control. It is proposed that the pulsatile nature of movement
      and the tendency of muscle collectives to be activated as synergies reflect
      processes that the nervous system has evolved to reduce the dimensionality of
      motor control. We propose that the inferior olive simplifies the computation
      underlying motor control by biasing the activities of spinal and cranial motor
      systems so that discrete collectives of muscles are predisposed to contract at
      specific times during movement. The well-characterized oscillatory activity of
      olivary neurons is postulated to provide a pacemaking signal and to restrict the
      control process to particular moments in time while the process of electrotonic
      coupling and uncoupling of assemblies of olivary neurons is proposed to underlie
      the spatial distribution of synergic muscle activations. It is proposed that the
      olivocerebellar contribution to the control process is to allow movements to be
      executed rapidly in a feedforward manner, so that the need for sensory guidance
      and feedback is minimized.

PMID- 9193161
TI  - Is the cerebellum sensory for motor's sake, or motor for sensory's sake: the view
      from the whiskers of a rat?

PMID- 9193162
TI  - Cerebellar contributions to the acquisition and execution of learned reflex and
      volitional movements.

PMID- 9193163
TI  - Involvement of cerebellar cortex and nuclei in the genesis and control of
      unconditioned and conditioned eyelid motor responses.
AB  - The eyelid motor system of the cat was used here for the study of the kinetic
      properties of reflex and conditioned lid movements, and of the role played by the
      cerebellum in the acquisition and/or performance of both types of motor
      responses. Spontaneous blinks, eyelid reflex responses, eye-guided lid movements
      and conditioned lid responses were recorded in alert cats in simultaneity with
      unitary and field electrical activity of cerebellar cortex and nuclear zones
      related to the eyelid motor system. Results indicate that nuclear unitary
      activity does not precede unconditioned or conditioned lid responses, but that
      cerebellar nuclei are directly involved in the performance of the late components
      of reflex lid movements and in the acquisition of conditioned lid responses.

PMID- 9193164
TI  - A new functional role for cerebellar long-term depression.

PMID- 9193165
TI  - On the role of the cerebellum and basal ganglia in cognitive signal processing.

PMID- 9193166
TI  - Dentate output channels: motor and cognitive components.

PMID- 9193167
TI  - The genetic basis of hereditary ataxia.

PMID- 9193168
TI  - Cerebellar somatotopic representation and cerebro-cerebellar interconnections in
      ataxic patients.
AB  - Different methods of functional neuroimaging were used for studying somatotopic
      encoding of function in the cerebellum and for investigating cerebro-cerebellar
      interconnections in patients with cerebellar degeneration. fMRI showed, that the
      center of activation for hand function was located in the intermediate
      hemispheric portion of Larsell lobules H IV-V. Foot movements activated areas
      medial and anterior to the corresponding hand areas within Larsell lobules II
      III. Changed function in motor cortices could be demonstrated in patients with
      cerebellar degeneration as compared to normal controls by recording movement
      related cortical potentials (BP). In patients the motor potential was almost
      lacking and transcranial magnetic stimulation demonstrated enhancement of
      inhibitory mechanisms (prolonged postexcitatory inhibition) in the motor cortex.
      PET-findings suggested, that both effects are correlated to increased activity of
      inhibitory interneurons. Cerebellar patients showed increased activation in
      relation to movements in the SMA and basal ganglia and reduced activation in the
      cerebellum and lateral premotor areas. It could be speculated, that compensatory
      mechanisms are the reason for a stronger activation of the medial premotor
      system, including SMA, in patients with cerebellar degeneration. On the basis of
      our results it appears, that the cerebellum facilitates the lateral premotor
      system areas much more than it does the medial areas.

PMID- 9193169
TI  - Buspirone, a serotonergic 5-HT1A agonist, is active in cerebellar ataxia. A new
      fact in favor of the serotonergic theory of ataxia.
AB  - We have previously proposed a serotonergic hypothesis for cerebellar ataxia and
      mentioned that the levorotatory form of 5-hydroxytryptophan, a serotonin
      precursor, is partially active in subtypes of cerebellar ataxia, including
      cerebellar cortical atrophy (CCA). It has been demonstrated that 5-HT1A
      serotonergic receptors play an important role in the control of Purkinje cells
      discharges and in the inhibition of the release of glutamate by cerebellar
      glutamatergic terminals. To test further the serotonergic hypothesis of
      cerebellar ataxia, we administered buspirone, a 5-HT1A agonist usable in human
      medicine, in a randomized double blind drug placebo trial for 4 months. Nineteen
      patients with CCA were included; nine patients were given placebo and 10
      Buspirone, at the mean dose of 0.69 mg/kg. The evaluation of ataxia was based on
      a static and a kinetic ataxia scale, fully quantitative measures and the
      evaluation of the sway path and area at posturography. At 4 months, a significant
      effect of buspirone was observed for drug induced gains of the kinetic score, two
      items of the static score, and the maximum duration of standing upright with feet
      together. These results indicate that a novel chemical therapeutic approach is
      possible for cerebellar ataxia; moreover, they support the existence of a link
      between cerebellar ataxia and disturbances of the serotonergic cerebellar system,
      especially a serotonergic deficit.

PMID- 9193170
TI  - Relationships, individual differences, and children's use of literate language.
AB  - BACKGROUND: Research in children's oral language and early literacy learning
      currently stresses the facilitative role of social context. Social context in
      this literature is typically treated on a macro-level, e.g., mother-child
      interaction or peer interaction. We present a more differentiated model of peer
      influences on children's learning one oral language register, 'literate
      language'. Literate language, which predicts school-based literacy, is defined as
      talk about language and literacy. AIMS: We suggest that children's temperament
      and their close relationships, in the form of friendships, play important roles
      in literate language learning. We present separate models for friends and
      nonfriends and posit that literate language is learned more effectively between
      friends because of the emotional tenor of this relationship. When they are with
      friends children, even those that might be considered 'difficult', disagree,
      resolve disagreements, then express emotions indicative of social understanding.
      Reflection upon emotion states, in turn, leads to literate language. SAMPLE: The
      sample comprised 33 males and 23 females attending American kindergarten classes,
      with a mean age of 65 months. METHODS: Dyads of same gender and race were
      observed 12 times across the school year during which time samples of oral
      language were taken. Measures of children reading and writing were also
      collected. RESULTS: The data support our model, and the friendship model
      accounting for more of the variance in literate language (R2 = .69) than did the
      nonfriend model (R2 = .43). CONCLUSIONS: Children with friends engage in the sort
      of conceptual conflict and resolutions which maximise use of literate language.
      This context seems particularly important for 'difficult' children. Future
      research should continue to examine the interface between individual and group
      levels variables.

PMID- 9193171
TI  - Dramatic play: a format for 'literate' language?
AB  - BACKGROUND: Research literature discussing the possibility of a relationship
      between dramatic play and literacy development in school beginners has evoked
      interest in the context of the formalisation of early years curriculum,
      particularly relationships between oral syntactic competence in preschool
      children and later reading ability. AIMS: The aim of the present study was to
      investigate possible differences in syntax between sociodramatic play and other
      play activities in small play groups. It was predicted that the language in
      sociodramatic play would be more 'literate', i.e., more decontextualised,
      explicit and linguistically elaborated. The hypothesis tested was that
      sociodramatic play elicits more advanced syntactic language in children. SAMPLES:
      Six children (six-year-olds) in groups of three girls and three boys were
      observed in 11 free play episodes (five sociodramatic play episodes and six other
      group play episodes). Approximately 100 utterances from each child in each play
      category were analysed. The children had normal intelligence and language
      ability, and had a middle class background. METHODS: The play groups were
      observed during indoor free play in a playroom equipped for family play and with
      different toys. No instructions were given. The observations were video- and
      audiotaped and the children's utterances transcribed and analysed syntactically,
      i.e., utterance types (complexity and completeness), sentence adverbials and
      expansions. Chi-square was used to test for statistically significant differences
      in children's use of syntax. RESULTS: The children's language turned out to be
      significantly more advanced and 'literate' with more syntactically complete and
      complicated utterances, use of explicit references and elaborated nominal groups
      in sociodramatic play than in any other play activity. CONCLUSIONS: The demands
      of conveying meaning to peers in dramatic play contexts seem to provide children
      with opportunities to practise 'literate' language, language that is similar to
      what is demanded when writing for an absent audience.

PMID- 9193172
TI  - Pupils' self assessments of academic attainment at 7, 11 and 16 years: effects of
      sex and ethnic group.
AB  - BACKGROUND: There is much concern with group differences in educational
      attainment in school. Better understanding of pupils' academic ability
      perceptions promises to help understanding of differences in attainment. AIMS:
      The aim of this paper is to examine ethnic and sex differences in academic self
      assessments at 7, 11 and 16 years, and ethnic and sex differences in the degree
      of under and overestimation of self assessment. SAMPLES: Results come from a
      longitudinal study of white and black UK pupils in inner London schools. Samples
      sizes at 7, 11 and 16 years were 133, 175, 108 respectively. METHODS: Self
      assessments, other self report data and attainments were collected at each age.
      RESULTS: White pupils by the end of junior and secondary school were less
      positive about their own attainments, and about themselves at school. While black
      girls showed confidence in their attainments, and had the highest attainments in
      reading/English, white girls tended to underestimate and have little confidence
      in their school attainments.

PMID- 9193173
TI  - William Stewart Halsted. Our surgical heritage.

PMID- 9193174
TI  - Major bile duct injuries during laparoscopic cholecystectomy. Follow-up after
      combined surgical and radiologic management.
AB  - OBJECTIVE: The authors provide the results of follow-up evaluation after combined
      surgical and radiologic management of 89 patients with major bile duct injuries
      during laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: The incidence and
      mechanism of injury of major bile duct injuries during laparoscopic
      cholecystectomy has been clearly defined. Furthermore, a number of series have
      described the management of these injuries by surgical, endoscopic, and
      radiologic techniques with excellent short-term results. Long-term follow-up
      data, however, are lacking in the management of these injuries. METHODS: Data
      were collected prospectively on 89 patients treated at a single institution with
      major bile duct injuries after laparoscopic cholecystectomy managed between July
      1, 1990, and July 1, 1996. Patients referred with injuries underwent early
      percutaneous transhepatic cholangiography and biliary drainage. Based on the
      cholangiographic appearance and clinical situation, patients were managed by
      either percutaneous balloon dilatation or surgical reconstruction with a Roux-en
      Y hepaticojejunostomy with transanastomotic stenting. Follow-up was obtained by
      personal interview during October 1996. RESULTS: Two patients died without an
      attempt at definitive therapy. Both deaths were caused by sepsis and multisystem
      organ failure present at the time of transfer to the authors' institution. The
      remaining 87 patients were managed initially by either balloon dilatation (N =
      28) or surgical reconstruction (N = 59). Ten patients have not completed
      treatment and still have biliary stents in place. Evaluation of 25 patients
      completing treatment after balloon dilatation (mean follow-up, 27.8 months)
      showed a success rate of 64%. Evaluation of 52 patients completing treatment
      after surgical reconstruction (mean follow-up, 33.4 months) showed a success rate
      of 92%. All failures were managed successfully by either surgical reconstruction
      or balloon dilatation. CONCLUSIONS: Major bile duct injuries can be managed
      successfully by combined surgical and radiologic techniques. This series
      provides, for the first time, significant follow-up on a large number of patients
      with overall success rates of 64% after balloon dilatation and 92% after surgical
      reconstruction. The combination of surgery and balloon dilatation resulted in a
      successful outcome in 100% of patients treated.

PMID- 9193175
TI  - Orthotopic liver transplantation for primary sclerosing cholangitis. A 12-year
      single center experience.
AB  - OBJECTIVE: The purpose of this study was to analyze a single center's 12-year
      experience with 127 orthotopic liver transplantations (OLT) for primary
      sclerosing cholangitis (PSC). SUMMARY BACKGROUND DATA: Primary sclerosing
      cholangitis is a chronic cholestatic liver disease of unknown origin that occurs
      most commonly in young men and is associated frequently (70-80%) with
      inflammatory bowel disease (IBD). Patients with PSC also are at risk for the
      development of cholangiocarcinoma (CCA) and those with IBD for colon carcinoma.
      Although the course of PSC is variable, it frequently is progressive, leading to
      cirrhosis and requirement for OLT. METHODS: The medical records of 127
      consecutive patients undergoing OLT for PSC from July 1, 1984, to May 30, 1996,
      were reviewed. Actuarial patient and graft survival was determined at 1,2, and 5
      years. The incidence and outcome of patients with CCA, recurrent sclerosing
      cholangitis, and post-transplant colon carcinoma was determined. Results were
      analyzed by way of stepwise Cox regression to determine the statistical strength
      of independent associations between pretransplant covariates and patient
      survival. The median follow-up period was 3.01 years. Incidental
      cholangiocarcinoma (ICCA) was defined as a tumor < 1 cm in size that was
      discovered at the time of pathologic sectioning of the explanted liver. RESULTS:
      Ninety-two patients (72%) had associated IBD. Seventy-nine (62%) had undergone
      previous biliary tract surgery. One hundred seven patients (84%) received a
      single graft, whereas 20 patients (16%) required 22 retransplants. Patients
      received either cyclosporine- (n = 76) or tacrolimus- (n = 51) based
      immunosuppression. The 1-, 2-, and 5-year actuarial patient survivals were 90%,
      86%, and 85%, respectively, whereas graft survival was 82%, 77%, and 72%,
      respectively. The presence of previous biliary surgery had no effect on patient
      survival. Ten patients (8%) had ICCA and their survival was not significantly
      different from patients without ICCA (100%, 83%, and 83% at 1, 2, and 5 years,
      respectively). Four patients were known to have CCA at the time of OLT, all
      recurred within 6 months, and had a significantly worse outcome (p < 0.0001).
      Recurrent sclerosing cholangitis developed in 11 patients (8.6%). The patient and
      graft survival in this group was not different from those in whom recurrence did
      not develop (patient; 100%, 90%, and 90%; graft: 80%, 70%, and 52%). Thirty
      patients (23%) underwent colectomy after liver transplantation for dysplasia
      carcinoma or symptomatic colitis. Of the nine covariates entered into the Cox
      multivariate regression analysis, only common bile duct frozen section biopsy
      specimen showing CCA was predictive of a survival disadvantage. CONCLUSIONS:
      Liver transplantation provides excellent patient and graft survival rates for
      patients affected with PSC independent of pretransplant biliary tract surgery.
      Incidental cholangiocarcinoma does not affect patient survival significantly.
      However, known CCA or common duct frozen section biopsy specimen or both showing
      CCA are associated with poor recipient survival, and OLT should be proscribed in
      these cases. Recurrent PSC occurs in approximately 9% of cases but does not
      affect patient survival. Post-transplant colectomy does not affect patient
      survival adversely.

PMID- 9193176
TI  - Clinical experience with a bioartificial liver in the treatment of severe liver
      failure. A phase I clinical trial.
AB  - OBJECTIVE: The purpose of this study was to develop a bioartificial liver (BAL)
      to treat patients with severe liver failure until they can be either transplanted
      or recover spontaneously. SUMMARY BACKGROUND DATA: Severe acute liver failure is
      associated with high mortality. Liver transplantation has emerged as an effective
      therapy for patients who did not respond to standard management. However, because
      of the donor organ shortage and urgent need for transplantation, many patients
      die before they can be transplanted and others do not survive after
      transplantation, primarily because of intracranial hypertension. METHODS: Three
      groups of patients with severe acute liver failure were treated with the BAL. In
      group 1 (n = 18) were patients with fulminant hepatic failure (FHF), in group 2
      (n = 3) were patients with primary nonfunction (PNF) of a transplanted liver, and
      in group 3 (n = 10) were patients with acute exacerbation of chronic liver
      disease. Patients in groups 1 and 2 were candidates for transplantation at the
      time they entered the study, whereas patients in group 3 were not. RESULTS: In
      group 1, 16 patients were "bridged" successfully to transplantation, 1 patient
      was bridged to recovery without a transplant, and 1 patient died because of
      concomitant severe pancreatitis. In group 2, all patients were bridged
      successfully to retransplantation. In group 3, two patients were supported to
      recovery and successful transplants at later dates; the other eight patients,
      although supported temporarily with the BAL, later died because they were not
      candidates for transplantation. CONCLUSIONS: The authors' clinical experience
      with the BAL has yielded encouraging results. A randomized, controlled,
      prospective trial (phase II-III) is being initiated to determine the efficacy of
      the system.

PMID- 9193177
TI  - Laparoscopic adrenalectomy. A new standard of care.
AB  - OBJECTIVE: The authors review their experience with laparoscopic adrenalectomy in
      patients with benign adrenal neoplasms. Efficacy, safety, and cost effectiveness
      of the procedure are examined. BACKGROUND: Laparoscopic adrenalectomy is
      replacing open adrenalectomy in some medical centers as the standard surgical
      approach for uncomplicated tumors. However, laparoscopic adrenalectomy often is
      considered more difficult and more expensive than traditional "open" surgery.
      METHODS: Perioperative and postoperative records as well as hospital charges from
      the first 19 patients undergoing laparoscopic unilateral adrenalectomies at the
      authors' medical institutions were examined and compared with 19 patients who
      underwent open unilateral adrenalectomies. RESULTS: None of the 19 patients
      undergoing unilateral laparoscopic adrenalectomy required conversion to open
      adrenalectomy. Mean operative times as well as total hospital charges were
      similar in those patients undergoing either laparoscopic or open adrenalectomy.
      However, the morbidity and postoperative length of hospital stay were
      significantly less in those patients undergoing laparoscopic adrenalectomy.
      CONCLUSIONS: Laparoscopic adrenalectomy can be performed safety and with the
      benefits associated with minimally invasive surgery. In addition, the procedure
      is cost effective. These factors suggest that laparoscopic adrenalectomy should
      be the preferential surgical technique for benign adrenal disease.

PMID- 9193178
TI  - Congenital aortic valve disease. Improved survival and quality of life.
AB  - OBJECTIVE: The purpose of the study was to assess the effect of recent trends in
      surgical management, including use of the Ross Operation, on improved survival
      and quality of life in patients treated surgically for aortic valve (AV) disease
      at Oklahoma Children's Hospital. BACKGROUND: Surgical treatment of congenital AV
      disease has proved to be palliative, but newer procedures may be improving
      outcomes. METHODS: A retrospective review of 301 patients, age 1 day to 26 years
      (median, 5 years), having a surgical AV procedure or aortic balloon valvuloplasty
      at Children's Hospital of Oklahoma between 1960 and February 1996, was conducted.
      Information was collected on all prior and subsequent operations, and follow-up
      within 1 year was 96% complete. RESULTS: Survival for all patients was 90% +/- 2%
      at age 10 years and 73% +/- 8% at age 25. By age 5, 52% +/- 4% had required an AV
      procedure, 89% +/- 3% by age 15. Patient survival was affected adversely by the
      diagnosis of valvar aortic stenosis, 79% +/- 6% at age 25 compared to 95% +/- 4%
      for subvalvar aortic stenosis or aortic insufficiency (p = 0.01). The AV
      morphology did not affect survival, but patients with a bicuspid or unicuspid
      valve required operative intervention at an earlier age. Survival after autograft
      replacement of the AV (Ross Operation) was significantly better than for other
      types of valve replacement (p = 0.0043). Quality of life as assessed by need for
      reoperation favors the use of the Ross Operation, with freedom from reoperation
      at 9 years of 87% +/- 7% compared to 55% +/- 5% in all patients after first AV
      surgery (p = 0.003). CONCLUSIONS: The Ross Operation appears to have a
      significant advantage in survival and quality of life in children requiring a
      valve replacement as a first operation or after a prior AV procedure.

PMID- 9193179
TI  - Sites of recurrence and long-term results of redo surgery.
AB  - OBJECTIVE: The authors determined whether carotid endarterectomy in patients with
      recurrent stenosis could provide durable stroke prevention with acceptable
      perioperative risk. SUMMARY BACKGROUND DATA: Balloon angioplasty and stenting are
      being advocated for recurrent stenosis because of the presumption that
      reoperation is unsafe with poor results. METHODS: The authors retrospectively
      reviewed their experience with 67 patients undergoing 74 operations for recurrent
      stenosis in a recent 11-year period. This represented 8.4% of 883
      endarterectomies performed during the same period. RESULTS: At original
      operation, 55% had primary closure and 45% were patched. Reoperation was
      performed for amaurosis fugax and transient ischemic attack (45%), post-stroke
      (7%), global ischemia (10%), and asymptomatic severe occlusive disease (35%).
      Four patients (6%) undergoing simultaneous cardiac procedures were excluded from
      further analysis. Mean duration between primary and first redo operation was 78
      months (range, 1-240 months). The 30-day combined mortality and stroke morbidity
      was 2.8%, evenly divided with 1.4% stroke and 1.4% mortality rates. Recurrent
      disease occurred predominantly (69%) in the previous endarterectomy site. Follow
      up ranged from 1 to 162 months (mean, 48.2). Seventeen deaths occurred, of which
      10 (59%) were cardiac. Two late ipsilateral neurologic events and four late
      contralateral events occurred. Two patients required third ipsilateral
      reoperation. Life-table analysis shows the ipsilateral stroke-free rate at 5
      years to be 93.6% CONCLUSIONS: Recurrent stenosis occurs either proximal to or in
      the previous endarterectomy site in the majority of patients. Recurrent stenosis
      can be treated surgically with low morbidity and mortality and durable long-term
      stroke prevention. The presumption that results of redo carotid surgery are poor
      is disproved.

PMID- 9193180
TI  - Popliteal artery trauma. Systemic anticoagulation and intraoperative thrombolysis
      improves limb salvage.
AB  - OBJECTIVE: This study was conducted to evaluate those factors associated with
      popliteal artery injury that influence amputation, with emphasis placed on those
      that the surgeon can control. SUMMARY BACKGROUND DATA: Generally accepted factors
      impacting amputation after popliteal artery injury include blunt trauma,
      prolonged ischemic times, musculoskeletal injuries, and venous disruption.
      Amputation ultimately results from microvascular thrombosis and subsequent tissue
      necrosis, predisposed by the paucity of collaterals around the knee. METHODS:
      Patients with popliteal artery injuries over the 10-year period ending November
      1995 were identified from the trauma registry. Preoperative (demographics,
      mechanism and severity of injury, vascular examination, ischemic times) and
      operative (methods of arterial repair, venous repair-ligation, anticoagulation
      thrombolytic therapy, fasciotomy) variables were studied. Severity of extremity
      injury was quantitated by the Mangled Extremity Severity Score (MESS).
      Amputations were classified as primary (no attempt at vascular repair) or
      secondary (after vascular repair). After univariate analysis, logistic regression
      analysis was performed to identify the independent risk factors for limb loss.
      RESULTS: One hundred two patients were identified; 88 (86%) were males and 14
      (14%) were females. Forty injuries resulted from blunt and 62 from penetrating
      trauma. There were 25 amputations (25%; 11 primary and 14 secondary). Patients
      with totally ischemic extremities (no palpable or Doppler pulse) more likely were
      to be amputated (31% vs. 13%; p < 0.04). All requiring primary amputations had
      severe soft tissue injury and three had posterior tibial nerve transection; the
      average MESS was 7.6. Logistic regression analysis identified independent factors
      associated with secondary amputation: blunt injury (p = 0.06), vein injury (p =
      0.06), MESS (p = 0.0001), heparin-urokinase therapy (p = 0.05). There were no
      complications with either heparin or urokinase. CONCLUSIONS: Minimizing ischemia
      is an important factor in maximizing limb salvage. Severity of limb injury, as
      measured by the MESS, is highly predictive of amputation. Intraoperative use of
      systemic heparin or local urokinase or both was the only directly controllable
      factor associated with limb salvage. The authors recommend the use of these
      agents to maximize limb salvage in association with repair of popliteal artery
      injuries.

PMID- 9193181
TI  - Is circulating endotoxin the trigger for the systemic inflammatory response
      syndrome seen after injury?
AB  - OBJECTIVE: Patients with severe traumatic or burn injury and a mouse model of
      burn injury were studied early after injury to determine the relation of plasma
      endotoxin (lipopolysaccharide [LPS]) to the production of proinflammatory
      cytokines and subsequent resistance to infection. SUMMARY BACKGROUND DATA:
      Elevated levels of plasma LPS have been reported in patients after serious
      injury. It has been suggested that circulating LPS may be a trigger for increased
      proinflammatory cytokine production and may play a role in the septic syndromes
      seen in a substantial portion of such patients. Yet, despite multiple reports of
      leakage of LPS from the gut and bacterial translocation after injury in animal
      models, there is little direct evidence linking circulating LPS with production
      of inflammatory mediators. METHODS: The authors studied serial samples of
      peripheral blood from 10 patients with 25% to 50% surface area burns and 8 trauma
      patients (injury Severity Score, 25-57). Patients were compared with 18 healthy
      volunteers. The study was focused on the first 10 days after injury before the
      onset of sepsis or the systemic inflammatory response syndrome. Plasma samples
      were assayed for LPS, and adherent cells from the blood were studied for basal
      and LPS-stimulated production of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). The correlation of
      increased plasma LPS with TNF-alpha production was studied as was the association
      of increased plasma LPS and increased TNF-alpha production with subsequent septic
      complications. We also studied a mouse model of 25% burn injury. Burn mice were
      compared with sham burn control subjects. Plasma samples were assayed at serial
      intervals for LPS, and adherent cells from the spleens were studied for basal-
      and LPS-stimulated production of TNF-alpha, IL-1 beta, and IL-6. Expression of
      the messenger RNAs for IL-1 beta and TNF-alpha also was measured. The relation of
      increased TNF-alpha production with mortality from a septic challenge, cecal
      ligation and puncture (CLP), was determined. Finally, the effect of
      administration of LPS to normal mice on subsequent mortality after CLP and on TNF
      alpha production was studied. RESULTS: Elevated plasma LPS (> 1 pg/mL) was seen
      in 11 of the 18 patients within 10 days of injury and in no normal control
      subjects. In this period, patients as compared with control subjects showed
      increased stimulated production of TNF-alpha, IL-1 beta, and IL-6. Increased TNF
      alpha production was not correlated with elevated plasma LPS in the same
      patients. Neither increased plasma LPS nor increased TNF-alpha production early
      after injury was correlated with subsequent development of systemic inflammatory
      response syndrome or sepsis in the patients. Burn mice, as compared with sham
      burn control subjects, showed elevated plasma LPS levels chiefly in the first 3
      days after injury. Increased stimulated production of proinflammatory cytokines
      by adherent splenocytes from the burn mice also was seen at multiple intervals
      after injury and did not correlate with mortality from CLP. Increased production
      of TNF-alpha and IL-1 beta was associated with increased expression of messenger
      RNAs for these cytokines. Finally, two doses of 1 ng LPS administered 24 hours
      apart to normal mice had no effect on mortality from CLP performed 7 days later
      nor on the production of TNF-alpha at the time of CLP. CONCLUSIONS: These
      findings call into question the idea that circulating LPS is the trigger for
      increased proinflammatory cytokine production, systemic inflammatory response
      syndrome, and septic complications in injured patients.

PMID- 9193182
TI  - Surgical management of primary cutaneous melanomas of the hands and feet.
AB  - OBJECTIVE: The purpose of the study was to investigate the surgical management of
      cutaneous melanomas of the hands and feet. SUMMARY BACKGROUND DATA: Prior studies
      suggest that patients with melanomes > 1-mm thick should be treated with excision
      with a 2-cm margin and undergo elective lymphadenectomy in selected
      circumstances. These recommendations are based primarily on data from melanomas
      of the trunk and extremities. Melanomas of the hands and feet are less common and
      less well studied. They pose a surgical challenge because primary wound closure
      often is difficult, and the incidence and management of regional node metastases
      are unclear. METHODS: Charts of patients with melanomas of the hands or feet
      treated at the Massachusetts General Hospital between 1980 and 1994 were reviewed
      retrospectively. Local recurrence rates and the incidence of regional node
      metastases were analyzed as a function of histology, margin of excision, and
      microscopic thickness of the melanoma. RESULTS: Data from 116 patients (39 men,
      77 women) with melanomas of the hands (n = 26) and feet (n = 90) were evaluated.
      Pathologic diagnoses were: acral lentiginous melanoma (48 patients); subungual
      melanoma (13 patients), and skin of dorsum of the hand or foot (n = 55). Digital
      amputation was required in all 13 patients with subungual melanoma to maintain
      local control; still, nodal metastases developed in 46% of patients within 1
      year. Seventy-one percent of patients with acral lentiginous melanoma presented
      with lesions > or = 1.5 mm, and nodes or systemic disease or both developed in
      56% of patients. Acral lentiginous melanoma lesions < 1.5-mm thick were treated
      principally by excision with a 1-cm margin; a local recurrence or metastases did
      not develop in any of the patients. None of the patients with melanomas on the
      dorsum of the hand or foot < 1.5-mm thick had a local recurrence, but regional or
      systemic disease developed in > 50%. Local control in patients with lesions > 1.5
      mm thick frequently required skin grafting or amputation. The majority of
      patients with melanomas > or = 1.5 mm in thickness undergoing elective lymph node
      dissection had histologically positive nodes for melanoma. CONCLUSIONS: Melanomas
      of the hands and feet < 1.5-mm thick have a low incidence of nodal metastases and
      are treated effectively with wide excision of the primary with a 1-cm margin.
      Thicker melanomas are associated with a > 50% rate of regional or systemic
      failure. In the absence of metastatic disease, these individuals should undergo
      local excision with a 2-cm margin and intraoperative lymphatic mapping followed
      by lymphadenectomy if the sentinel node is positive.

PMID- 9193183
TI  - Mortality determinants in massive pediatric burns. An analysis of 103 children
      with > or = 80% TBSA burns (> or = 70% full-thickness).
AB  - OBJECTIVE: Survivors and nonsurvivors among 103 consecutive pediatric patients
      with massive burns were compared in an effort to define the predictors of
      mortality in massively burned children. SUMMARY BACKGROUND DATA: Predictors of
      mortality in burns that are used commonly are age, burn size, and inhalation
      injury. In the past, burns over 80% of the body surface area that are mostly full
      thickness often were considered fatal, especially in children and in the elderly.
      In the past 15 years, advances in burn treatment have increased rates of survival
      in those patients treated at specialized burn centers. The purpose of this study
      was to document the extent of improvement and to define the current predictors of
      mortality to further focus burn care. METHODS: Beginning in 1982, 103 children
      ages 6 months to 17 years with burns covering at least 80% of the body surface
      (70% full-thickness), were treated in the authors' institution by early excision
      and grafting and have been observed to determine outcome. The authors divided
      collected independent variables from the time of injury into temporally related
      groups and analyzed the data sequentially and cumulatively through univariate
      statistics and through pooled, cross-sectional multivariate logistic regression
      to determine which variables predict the probability of mortality. RESULTS: The
      mortality rate for this series of massively burned children was 33%. Lower age,
      larger burn size, presence of inhalation injury, delayed intravenous access,
      lower admission hematocrit, lower base deficit on admission, higher serum
      osmolarity at arrival to the authors' hospital, sepsis, inotropic support
      requirement, platelet count < 20,000, and ventilator dependency during the
      hospital course significantly predict increased mortality. CONCLUSIONS: The
      authors conclude that mortality has decreased in massively burned children to the
      extent that nearly all patients should be considered as candidates for survival,
      regardless of age, burn size, presence of inhalation injury, delay in
      resuscitation, or laboratory values on initial presentation. During the course of
      hospitalization, the development of sepsis and multiorgan failure is a harbinger
      of poor outcome, but the authors have encountered futile cases only rarely. The
      authors found that those patients who are most apt to die are the very young,
      those with limited donor sites, those who have inhalation injury, those with
      delays in resuscitation, and those with burn-associated sepsis or multiorgan
      failure.

PMID- 9193184
TI  - Skin-sparing mastectomy. Oncologic and reconstructive considerations.
AB  - OBJECTIVE: The authors compared skin-sparing mastectomy and traditional
      mastectomy both followed by immediate reconstruction in the treatment of breast
      cancer. SUMMARY BACKGROUND DATA: Skin-sparing mastectomy is used increasingly in
      the treatment of breast cancer to improve the aesthetic results of immediate
      reconstruction. The oncologic and reconstructive outcomes of this procedure have
      never been analyzed closely. METHODS: Institutional experience with 435
      consecutive patients who underwent total mastectomy and immediate reconstruction
      from January 1989 through December 1994 was examined. Mastectomies were
      stratified into skin-sparing (SSM) and non-skin-sparing (non-SSM) types. RESULTS:
      Three hundred twenty-seven SSMs and 188 non-SSMs were performed. The mean follow
      up was 41.3 months (SSM, 37.5 months, non-SSM, 48.2 months). Local recurrences
      from invasive cancer occurred after 4.8% of SSMs versus 9.5% of non-SSMs. Sixty
      five percent of patients who underwent SSMs had nothing performed on the opposite
      breast versus 45% in the group of patients who underwent non-SSM (p = 0.0002).
      Native skin flap necrosis occurred in 10.7% of patients who underwent SSMs versus
      11.2% of patients who underwent non-SSMs. CONCLUSIONS: Skin-sparing mastectomy
      facilitates immediate breast reconstruction by reducing remedial surgery on the
      opposite breast. Native skin flap necrosis is not increased over that seen with
      non-SSM. Skin-sparing mastectomies can be used in the treatment of invasive
      cancer without compromising local control.

PMID- 9193185
TI  - Is surgical management compromised in elderly patients with breast cancer?
AB  - OBJECTIVE: The suggestion that breast cancer management is compromised in elderly
      patients had prompted our review of the results of policies regarding screening
      and early detection of breast cancer and the adequacy of primary treatment in
      older women (> or = 65 years of age) compared to younger women (40 to 64 years of
      age). SUMMARY BACKGROUND DATA: Although breast cancer in elderly patients is
      considered biologically less aggressive than similar staged cancer in younger
      counterparts, outcome still is a matter of stage and adequate treatment of
      primary cancer. For many reasons, physicians appear reluctant to treat elderly
      patients according to the same standards used for younger patients. There is even
      government-mandated alterations in early detection programs. Thus, since 1993,
      Medicare has mandated screening mammography on a biennial basis for women older
      than 65 year of age compared to the current accepted standard of yearly
      mammograms for women older than 50 years of age. Using State Health Department
      and tumor registry data, the authors reviewed screening practice and management
      of elderly patients with primary breast cancer to determine the effects of age on
      screening, detection policies (as reflected in stage at diagnosis), treatment
      strategies, and outcome. METHODS: Data were analyzed from 5962 patients with
      breast cancer recorded in the state-wide Tumor Registry of the Hospital
      Association of Rhoda Island between 1987 and 1995. The focus of the data
      collection was nine institutions with established tumor registries using AJCC
      classified tumor data. Additional data were provided by the State Health
      Department on screening mammography practice in 2536 women during the years 1987,
      1989, and 1995. RESULTS: The frequency of mammographic screening for all averaged
      40% in 1987, 52% in 1987, and 63% in 1995. In the 65-year-old and older patients,
      the frequency of screening was 34% in 1987, 45% in 1989, and 48% in 1995, whereas
      in the 40- to 49-year-old age group, the frequency of mammography was 47% in
      1987, 61% in 1989, and 74% in 1995 (p < 0.001). There was a lower detection rate
      of preinvasive cancer in the 65-year-old and older patients, 8.8% versus 13.7% in
      patients within the 40- to 64-year-old age group (p < 0.001). There was a higher
      percentage of treatment by limited surgery among elderly patients with highly
      curable Stage IA and IB cancer with 26.6% having lumpectomy alone versus 9.4% in
      the younger patients. Five-year survival in that group was significantly worse
      (63%) than in patients treated by mastectomy (80%) or lumpectomy with axillary
      dissection and radiation (95%, < 0.001). A similar effect was seen in patients
      with Stage II cancer. CONCLUSIONS: Breast cancer management appears compromised
      in elderly patients (older than 65 years of age). Frequency of mammography
      screening is significantly less in elderly women older than 65 years of age.
      Early detection of preinvasive (curative cancers) is significantly less than in
      younger patients. The recent requirement by Medicare of mammography every other
      year may further reduce the opportunity to detect potentially curable cancers.
      Approximately 20% of patients had inferior treatment of favorable stage early
      primary cancer with worsened survival. Detection and treatment strategy changes
      are needed to remedy these deficiencies.

PMID- 9193186
TI  - Adenocarcinoma of the ampulla of Vater. A 28-year experience.
AB  - OBJECTIVE: The aim of this study were to review the experience with
      adenocarcinoma of the ampulla of Vater at The Johns Hopkins Hospital and to
      determine what factors influenced the long-term outcome in these patients.
      SUMMARY BACKGROUND DATA: Adenocarcinoma of the ampulla of Vater is the second
      most common periampullary malignancy. However, most series have relatively small
      numbers. As a result, analysis of factors influencing outcome has been limited.
      METHODS: From 1969 to 1996, 120 patients with adenocarcinoma of the ampulla of
      Vater were managed at The Johns Hopkins Hospital. Clinical, operative, and
      pathologic factors were correlated with morbidity and long-term survival. Factors
      influencing outcome were evaluated by univariate and multivariate analyses.
      RESULTS: Resection was performed in 106 patients (88%), and 105 of these patients
      (99%) underwent either pancreatoduodenal resection (n = 103) or total
      pancreatectomy (n = 2). Resection rate increased from 62% in the 1970s to 82% in
      the 1980s to 96% in the 1990s (p < 0.05). Overall mortality after resection was
      3.8% with no mortality in the 45 consecutive patients resected in the past 5
      years. Morbidity also decreased significantly (p < 0.05) from 70% before to 38%
      after December 1992. Five-year survival for resected patient was 38%. Factors
      favorably influencing long-term outcome were resection (p < 0.001), no
      perioperative blood transfusions (p < 0.05), negative lymph node status (p =
      0.05), and moderate or well-differentiated tumors (p < 0.05). In a multivariate
      analysis, the best predictor of prolonged survival was absence of intraoperative
      transfusion (p = 0.06, relative risk = 1.90, 95% confidence limits = 0.95-3.78).
      CONCLUSIONS: Compared to carcinoma of the pancreas, carcinoma of the ampulla of
      Vater has a higher resectability rate and a better prognosis. Early diagnosis is
      important because lymph node status influences survival. Careful operative
      dissection and avoidance of transfusions also improves long-term survival.

PMID- 9193187
TI  - Differential effects on portal and effective hepatic blood flow. A comparison
      between transjugular intrahepatic portasystemic shunt and small-diameter H-graft
      portacaval shunt.
AB  - OBJECTIVE: This study was undertaken to determine the effects of transjugular
      intrahepatic portasystemic shunt (TIPS) and small-diameter prosthetic H-graft
      portacaval shunt (HGPCS) on portal and effective hepatic blood flow. SUMMARY
      BACKGROUND DATA: Mortality after TIPS is higher than after HGPCS for bleeding
      varices. This higher mortality is because of hepatic failure, possibly a result
      of excessive diminution of hepatic blood flow. METHODS: Forty patients randomized
      prospectively to undergo TIPS or HGPCS had effective hepatic blood flow
      determined 1 day preshunt and 5 days postshunt using low-dose galactose
      clearance. Portal blood flow was determined using color-flow Doppler ultrasound.
      RESULTS: Treatment groups were similar in age, gender, and Child's class. Each
      procedure significantly reduced portal pressures and portasystemic pressure
      gradients. Portal flow after TIPS increased (21 mL/second +/- 11.9 to 31
      mL/second +/- 16.9, p < 0.05), whereas it remained unchanged after HGPCS (26
      mL/second +/- 27.7 to 14 mL/second +/- 41.1, p = n.s.). Effective hepatic blood
      flow was diminished significantly after TIPS (1684 mL/minute +/- 2161 to 676
      mL/minute +/- 451, p < 0.05) and was unaffected by HGPCS (1901 mL/ minute +/-
      1818 to 1662 mL/minute +/- 1035, p = n.s.). CONCLUSIONS: Both TIPS and HGPCS
      achieved significant reductions in portal vein pressure gradients. Portal flow
      increased after TIPS, although most portal flow was diverted through the shunt.
      Effective hepatic flow is reduced significantly after TIPS but well preserved
      after HGPCS. Hepatic decompensation and mortality after TIPS may be because, at
      least in part, of reductions in nutrient hepatic flow.

PMID- 9193190
TI  - Models to conceptualize risk factors for bulimia nervosa.

PMID- 9193189
TI  - Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant
      chemoradiation improves survival. A prospective, single-institution experience.
AB  - OBJECTIVE: This study was designed to evaluate prospectively survival after
      pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different
      postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy.
      SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor
      Study Group, adjuvant chemoradiation therapy has been recommended after
      pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process
      of the pancrease. However, many patients continue to receive no such therapy.
      METHODS: From October 1991 through September 1995, all patients with resected,
      pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of
      the pancreas were reviewed by a multidisciplinary group (surgery, radiation
      oncology, medical oncology, and pathology) and were offered three options for
      postoperative treatment after pancreaticoduodenectomy: 1) standard therapy:
      external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with
      two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500
      mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation
      therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic
      irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2
      per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no
      therapy: no postoperative radiation therapy or chemotherapy. RESULTS:
      Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death
      (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive
      therapy, and 53 patients declined therapy. The three groups were comparable with
      respect to race, gender, intraoperative blood loss, tumor differentiation, lymph
      node status, tumor diameter, and resection margin status. Univariate analyses
      indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence
      of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy
      were associated with significantly longer survival (p < 0.05). By Cox
      proportional hazards survival analysis, the most powerful predictors of outcome
      were tumor diameter, intraoperative blood loss, status of resection margins, and
      use of postoperative adjuvant therapy. The use of postoperative adjuvant
      chemoradiation therapy was a predictor of improved survival (median survival,
      19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive
      therapy group had no survival advantage when compared to that of the standard
      therapy group (median survival, 17.5 months vs. 21 months, p = not significant).
      CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival
      after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate
      process of the pancreas. Based on these survival data, standard adjuvant
      chemoradiation therapy appears to be indicated for patients treated by
      pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process
      of the pancreas. Intensive therapy conferred no survival advantage over standard
      therapy in this analysis.

PMID- 9193191
TI  - Risk factors for bulimia nervosa. A community-based case-control study.
AB  - BACKGROUND: Many apparently disparate risk factors have been implicated as causes
      of eating disorders. This study was designed to test the hypothesis that 2 broad
      classes of risk factors exist for bulimia nervosa: those that increase the risk
      for development of a psychiatric disorder in general and those that increase the
      risk of dieting. It was predicted that the latter are especially common among
      persons with bulimia nervosa. METHODS: A case-control design was used involving 2
      integrated comparisons. First, 102 subjects with bulimia nervosa were compared
      with 204 healthy control subjects without an eating disorder. Second, the same
      102 subjects with bulimia nervosa were compared with 102 subjects with other
      psychiatric disorders. To reduce sampling bias, the subjects were recruited
      directly from the community. A broad range of putative risk factors was assessed.
      RESULTS: The subjects with bulimia nervosa and the healthy control subjects
      differed in their rates of exposure to most of the putative risk factors. Far
      fewer differences were evident between the subjects with bulimia nervosa and the
      control subjects with other psychiatric disorders, although exposure to factors
      that were likely to increase the risk of dieting and to negative self-evaluation
      and certain parental problems (including alcohol use disorder) were substantially
      more common among those with bulimia nervosa. CONCLUSIONS: The findings support
      the hypothesis that bulimia nervosa is the result of exposure to general risk
      factors for psychiatric disorder and risk factors for dieting. An unexpected
      finding was the particularly high rates of premorbid negative self-evaluation and
      certain parental problems among those with bulimia nervosa.

PMID- 9193188
TI  - Pancreatic carcinoma cell killing via adenoviral mediated delivery of the herpes
      simplex virus thymidine kinase gene.
AB  - OBJECTIVE: Use of adenoviral mediated delivery of the herpes simplex virus
      thymidine kinase (HSV-TK) gene as a gene therapy strategy for carcinoma of the
      pancreas. SUMMARY BACKGROUND DATA: Expression of HSV-TK selectively sensitizes
      cells to the nucleoside analog ganciclovir (GCV). This strategy has been used to
      treat other compartmentalized tumor models. Therefore, the containment of
      pancreatic carcinoma makes it amenable to this gene therapy approach. METHODS: A
      recombinant adenoviral vector encoding the HSV-TK gene was used to induce GCV
      sensitivity and test the potential bystander effect in established pancreatic
      carcinoma cell lines and patient-derived tumor material. Additionally, Balb/C
      nude mice were injected intraperitoneally with human pancreatic carcinoma cells
      and treated with GCV (50 mg/kg per day) for 14 days. RESULTS: Expression of the
      HSV-TK gene elicited a significant bystander effect in the presence of GCV.
      Pancreatic tumor cells injected intraperitoneally into nude mice resulted in
      significant tumor formation. Treatment of animals with AdCMVHSV/HSV-TK and GCV
      induced a dramatic decrease in overall tumor burden for up to 8 weeks post-GCV
      treatment. CONCLUSIONS: Pancreatic carcinoma cells are highly susceptible to
      transduction with recombinant adenoviral vector and elicit a potent bystander
      effect on neighboring tumor cells. Additionally, in vivo treatment of tumor
      bearing animals results in dramatic reduction of overall tumor burden, thus
      providing the rationale for molecular chemotherapy of pancreatic carcinoma.

PMID- 9193192
TI  - Hormonal and subjective responses to intravenous meta-chlorophenylpiperazine in
      bulimia nervosa.
AB  - BACKGROUND: Several lines of evidence point to serotonergic abnormalities in
      patients with bulimia nervosa (BN). Our goal was to further examine central
      serotonergic function in bulimic patients using neuroendocrine and subjective
      responses to the postsynaptic serotonin receptor agonist meta
      chlorophenylpiperazine (mCPP). METHOD: Using a double-blind, randomized, placebo
      controlled design, we assessed neuroendocrine and subjective responses to
      intravenous mCPP (0.1 mg/kg) and placebo in 16 patients with BN, free of
      medication, and 14 normal control subjects. Plasma prolactin and cortisol levels
      were used as neuroendocrine measures, whereas subjective responses were measured
      using a visual analog scale of 10 different mood states. RESULTS: Compared with
      controls, the BN group exhibited blunted prolactin and net cortisol responses
      following mCPP challenge. Subjective responses, while preliminary, also differed
      between groups on items related to anxiety, calmness, and altered self-awareness.
      CONCLUSION: Evidence of dysfunction at or downstream of central serotonergic
      receptors in BN confirms and extends findings of prior research.

PMID- 9193194
TI  - Cerebral gray matter volume deficits after weight recovery from anorexia nervosa.
AB  - BACKGROUND: Structural changes have been observed in the brains of low-weight
      patients with anorexia nervosa (AN), including increased cerebrospinal fluid
      (CSF) volumes and decreased gray matter and white matter volumes. We hypothesized
      that subjects who are weight-recovered from AN would show elevated CSF volumes
      and reduced gray matter volumes compared with controls. METHODS: We used magnetic
      resonance imaging to compare the brains of 12 subjects who are weight-recovered
      from AN (time since weight recovery, 1-23 years) with those of 18 healthy control
      subjects and 13 low-weight patients with AN. Axial, dual-echo scans of the whole
      brain were segmented into gray matter, white matter, and CSF compartments by
      means of a computerized volumetric approach. Brain measures were corrected for
      the significant effects of intracranial volume and age, based on regression
      analysis of a larger group of 30 healthy female controls. RESULTS: Tests showed
      that the weight-recovered group had significantly greater CSF volumes and smaller
      gray matter volumes than the control group. By comparison with low-weight
      patients, the weight-recovered subjects had significantly smaller CSF volumes and
      significantly larger gray matter and white matter volumes. In the weight
      recovered group, neither the CSF elevations nor gray matter deficits were
      correlated with the length of time since weight recovery. CONCLUSIONS: The
      persistent gray matter volume deficits in subjects who are weight-recovered from
      AN suggest that there may be an irreversible component to the brain changes
      associated with the illness. The neuropathological features of this irreversible
      component have yet to be characterized.

PMID- 9193193
TI  - Decreased serotonin function in bulimia nervosa.
AB  - BACKGROUND: Evidence that serotonin-active antidepressant medications decrease
      binge eating in patients with bulimia nervosa has fueled interest in the
      hypothesis that abnormal serotonergic neurotransmitter function contributes to
      symptoms of the disorder. To evaluate this hypothesis, we employed
      pharmacological challenge testing to compare serotonin function in patients with
      bulimia nervosa and healthy controls. METHODS: Neuroendocrine response patterns
      were compared for 15 nonhospitalized, medication-free, normal-weight women with
      bulimia nervosa and 14 age-matched healthy female controls. Behavioral assessment
      included ratings of eating disorder symptoms, depression, and anxiety.
      Serotonergic response patterns were assessed by measuring the increase in serum
      prolactin concentration during 5 hours following single-dose, oral administration
      of 60 mg of d,l-fenfluramine hydrochloride (Pondimin). RESULTS: For patients with
      bulimia nervosa, the fenfluramine-stimulated increase in serum prolactin
      concentration was significantly less than for controls. Within the patient group,
      the frequency of binge eating episodes during the 4 weeks prior to the study
      exhibited a significant inverse correlation with serotonin-stimulated prolactin
      secretion. CONCLUSION: Our study provides new evidence that impaired central
      nervous system serotonergic responsiveness may contribute to the onset or
      maintenance of abnormal eating patterns in patients with bulimia nervosa.

PMID- 9193195
TI  - Psychosocial correlates of job strain in a sample of working women.
AB  - BACKGROUND: This study identifies potential mediators of job strain effects on
      health by determining whether psychosocial factors known to predict an increased
      risk of cardiovascular disease and all-cause mortality are higher among women who
      report high levels of job strain. METHODS: Measures of job strain and other
      psychosocial risk factors were obtained in a sample of 152 female employees of a
      local corporation. Canonical correlation and analyses of covariance were used to
      assess relationships between job demands and decision latitude and other
      psychosocial risk factors. RESULTS: A significant (P = .002) solution to the
      canonical correlation analysis showed that high job demands and low decision
      latitude were correlated with a pattern of psychosocial factors consisting of (1)
      increased levels of negative emotions like anxiety, anger, depression, and
      hostility; (2) reduced levels of social support; and (3) a preponderance of
      negative compared with positive feelings in dealings with coworkers and
      supervisors. This pattern was confirmed by analyses of covariance that adjusted
      for demographic and specific job characteristics. CONCLUSIONS: The canonical
      correlation analysis results provide empirical support for the job strain
      construct. The most important finding is that health-damaging psychosocial
      factors like job strain, depression, hostility, anxiety, and social isolation
      tend to cluster in certain individuals.

PMID- 9193196
TI  - Quetiapine in patients with schizophrenia. A high- and low-dose double-blind
      comparison with placebo. Seroquel Study Group.
AB  - BACKGROUND: Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical
      dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2
      (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with
      schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d).
      METHODS: In this multicenter, double-blind, placebo-controlled trial, 286
      patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were
      randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750
      mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or
      placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global
      Impression Severity of Illness item scores were the primary efficacy variables.
      Secondary efficacy variables included the BPRS positive-symptom cluster score,
      the Modified Scale for the Assessment of Negative Symptoms summary score (United
      States only), and the total score from the negative scale of the Positive and
      Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of
      covariance for change from baseline at end point with last observations carried
      forward. The model included baseline score (covariate), center, and treatment.
      Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the
      Barnes Akathisia Scale; abnormal involuntary movements were assessed using the
      Abnormal Involuntary Movement Scale. Frequency distributions of grouped change
      from-baseline scores were analyzed using chi 2 tests. RESULTS: Of 280 patients in
      whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high
      dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial
      completion, primarily because of treatment failure. Significant (P < .001, BPRS;
      P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS
      positive-symptom cluster) differences were identified between patients receiving
      high-dose quetiapine and placebo for both primary efficacy variables, with end
      point differences in the BPRS positive-symptom cluster score showing quetiapine's
      consistency in reducing positive symptoms. The reduction of negative symptoms was
      less consistent; high-dose quetiapine was superior on the Modified Scale for the
      Assessment of Negative Symptoms but not on the negative scale of the Positive and
      Negative Syndrome Scale. Quetiapine was well tolerated and did not induce
      extrapyramidal symptoms, sustained elevations of prolactin, or clinically
      significant changes in hematologic parameters. CONCLUSIONS: Quetiapine is an
      effective antipsychotic with a favorable safety profile. The optimum dose is
      probably greater than 250 mg/d.

PMID- 9193198
TI  - The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely
      psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group.
AB  - BACKGROUND: Based mainly on the selective antagonism of clozapine at D4 compared
      with D2 dopamine receptors, hopes have run high that a selective D4 dopamine
      receptor antagonist might improve the pharmacological treatment of patients with
      schizophrenia. We report, to our knowledge, the first multicenter study of the
      antipsychotic potential of a highly specific D4 dopamine receptor antagonist (ie,
      L-745,870) in patients with acute schizophrenia. METHODS: Thirty-eight acutely
      psychotic and neuroleptic responsive (by history) newly admitted inpatients with
      schizophrenia were randomized to 4 weeks of double-blind treatment (2:1) with
      either L-745,870 (n = 26), 15 mg/d, or placebo (n = 12) after a 3- to 5-day
      placebo run-in period. RESULTS: Overall, a greater percentage of patients
      receiving L-745,870 compared with patients receiving placebo discontinued the
      study for insufficient therapeutic response (32% vs 16%). At the end of 4 weeks
      by last observation carried forward analysis, the mean change from baseline to
      week 4 on the total Brief Psychiatric Rating Scale favored placebo (i.e., -8
      points [-15% change from baseline] vs -1 point [-2% change from baseline] for
      placebo vs L-745,870, P = .09). Similar differences in favor of placebo in
      changes from baseline mean scores were observed for the not carried forward
      analysis on the total Brief Psychiatric Rating Scale (P < .03), for not carried
      forward and last observation carried forward analyses on the sum of selected
      positive symptom items of the Brief Psychiatric Rating Scale, and for the
      Clinical Global Impression analysis (P = .03, last observation carried forward).
      A greater percentage of patients receiving L-745,870 had scores indicative of
      some level of worsening (compared with baseline) on the total Brief Psychiatric
      Rating Scale and the Clinical Global Impressions' Severity of Illness Scale as
      well as positive symptoms compared with those receiving placebo. CONCLUSION: The
      selective D4 dopamine receptor antagonist L-745,870 was ineffective as an
      antipsychotic for the treatment of neuroleptic responsive inpatients with acute
      schizophrenia.

PMID- 9193199
TI  - Schizophrenia after prenatal famine.

PMID- 9193197
TI  - Increased concentrations of presynaptic proteins in the cingulate cortex of
      subjects with schizophrenia.
AB  - BACKGROUND: Cytoarchitectural and neurochemical studies demonstrate
      disorganization in the cerebral cortex in schizophrenia, which perhaps underlies
      the severe behavioral disturbances of the disease. This neuronal disarray should
      be accompanied by synaptic abnormalities. As such, presynaptic proteins have
      proved valuable indexes of synaptic density and their concentrations have
      correlated markedly with synaptic loss. Our study sought to determine whether
      abnormalities exist in the concentrations of presynaptic proteins in the
      postmortem cerebral cortex of subjects with schizophrenia. METHODS: Presynaptic
      protein immunoreactivities were assessed in 4 different cerebrocortical regions
      derived from 16 elderly controls, 19 elderly subjects with schizophrenia, and 24
      subjects with Alzheimer's disease. Tissues were assayed with the monoclonal
      antibodies EP10 and SP4, which recognize synaptophysin, and the monoclonal
      antibodies SP6 and SP14, which detect syntaxin and synaptosomal-associated
      protein-25-kd immunoreactivities, respectively. RESULTS: In subjects with
      schizophrenia relative to controls, presynaptic proteins were increased in the
      cingulate cortex, but were unchanged in the temporal, frontal, and parietal
      cortices. In contrast, when cases with Alzheimer's disease were compared with
      controls, presynaptic proteins were decreased in the frontal, temporal, and
      parietal samples. CONCLUSIONS: These findings reveal changes in the synaptic
      organization of the cingulate cortex in schizophrenia relative to other areas
      examined. These changes are distinct from the deficits in presynaptic proteins
      observed in Alzheimer's disease.

PMID- 9193201
TI  - Assisted suicide.

PMID- 9193200
TI  - N-methyl-D-aspartate receptor hypofunction in schizophrenia could arise from
      reduced cortical connectivity rather than receptor dysfunction.

PMID- 9193202
TI  - On the nature of cost-savings treatment analysis.

PMID- 9193203
TI  - Cognitive function and the costs of Alzheimer disease. An exploratory study.
AB  - OBJECTIVE: To estimate the dollar savings in costs attainable from drug or other
      treatments for Alzheimer disease (AD) that stabilize or reverse patients'
      cognitive decline. METHODS: Medical and other disease-related utilization data
      were collected from the caregivers of 64 patients diagnosed as having probable
      AD. The quantities of utilization were priced at national levels to generate
      measures of illness costs. Costs per patient were then estimated as regression
      functions of scores on the Mini-Mental State Examination (MMSE), which was used
      as an index of patient cognitive function. Potential savings in illness costs
      were estimated by comparing predicted costs at various baseline and intervention
      level values of the patient's MMSE score. RESULTS: The potential savings in
      illness costs attainable from treatment are small for mildly and very severely
      demented patients with AD. However, for moderately to severely demented home
      dwelling patients having, say, an MMSE score of 7 at baseline, prevention of a 2
      point decline in the score would save about $3700 annually, and a 2-point
      increase in an MMSE score rather than a 2-point decline would save about $7100.
      CONCLUSION: Large savings in the costs of caring for moderately to severely
      demented home-dwelling patients with AD may be achievable from disease
      interventions that have minor effects on patients' cognitive status.

PMID- 9193204
TI  - Comparative evolution of Alzheimer disease, vascular dementia, and mixed
      dementia.
AB  - OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia
      (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western
      Ontario Dementia Study, which is a registry of cases of dementia seen for
      secondary and tertiary assessment in a university memory disorders clinica with
      extensive follow-up data and histopathological confirmation of clinical
      diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable
      AD, 12 patients with definite or probable VaD, and 36 patients with definite or
      probable mixed dementia. METHODS: Patients were grouped as having an early,
      moderate, or advanced stage of disease according to the extended scale for
      dementia (ESD). The ESD was subdivided into cognitive domains, and the domain
      scores were compared for each stage of disease by diagnostic category with the
      use of a 2-way analysis of variance with repeated measures. RESULTS: As expected,
      the scores in all domains decreased significantly with increasing severity. There
      was a significant difference in the decline in memory among the diagnostic groups
      (P = .02) that was mostly attributable to the difference between AD and mixed
      dementia (P = .03), with the difference between AD and VaD only approaching
      significance (P = .06). There was a similar finding for praxis. The interaction
      between diagnosis (AD and VaD) and severity was significant only for memory (P =
      .02), showing a less severe memory deficit at onset but a proportionately more
      rapid progression in VaD and arithmetic ability (AD and mixed dementia [P =
      .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly
      as assessed using cognitive domains obtained by subdivision of the ESD in a
      patient population derived from a memory clinic and by analyzing VaD as a single
      entity. Only memory impairment evolves differently between AD and VaD, with this
      depending on the severity. Memory is more severely impaired in the early stage of
      AD; however, with increasing severity of dementia, memory impairment in VaD
      accelerates and catches up with AD at the level of moderate impairment. The
      differences between AD and mixed dementia are greater than those between mixed
      dementia and VaD, suggesting an important role for the ischemic component of
      mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of
      distinguishing between AD and VaD, and more focused instruments may be required.
      Inherent bias in case selection may prevent extrapolation of these results to VaD
      in general, but the neuropsychological criteria for VaD may need to vary,
      depending on the severity.

PMID- 9193205
TI  - Reliability of the Washington University Road Test. A performance-based
      assessment for drivers with dementia of the Alzheimer type.
AB  - OBJECTIVE: To assess the reliability and stability of a standardized road test
      for healthy aging people and those with dementia of the Alzheimer type (DAT).
      DESIGN: A prospective study involving patients with DAT and age-matched healthy
      controls in which subjects' driving performance was evaluated by several raters
      in an initial and a follow-up road test. SETTING: Urban medical school and urban
      highways and streets. SUBJECTS: A convenience sample of 58 controls, 36 subjects
      with very mild DAT, and 29 subjects with mild DAT. RESULTS: Analysis of road test
      ability of controls (2 subjects [3%] failed the test), very mild DAT subjects (7
      subjects [19%] failed), and mild DAT subjects (12 subjects [41%] failed)
      disclosed a significant association between driving performance and dementia
      status (chi 2[4] = 20.65 [N = 123]; P < .001; Kendall tau-b = 0.306). Interrater
      reliability for assessment of driving performance ranged from kappa = 0.85 to
      0.96. One-month test-retest stability on the road test was 0.76 (quantitative
      scoring) and 0.53 (clinical judgment). CONCLUSIONS: Dementia adversely affects
      driving performance even in its mild stages, although some persons with DAT seem
      to drive safely for some time after disease onset. A traffic-interactive,
      performance-based road test that examines cognitive behaviors provides an
      accurate and reliable functional assessment of driving ability.

PMID- 9193206
TI  - Domain specificity of the subtests of the Mini-Mental State Examination.
AB  - OBJECTIVE: To examine the convergent and, for the first time to our knowledge,
      the divergent validity of 4 of the subtests of the Mini-Mental State Examination
      (MMSE): attention, naming, memory, and copy. METHODS: Participants included 126
      memory-impaired individuals (mean age, 74 years). Because the naming subtest
      showed no variability, we did not analyze it further. RESULTS: The convergent
      validity of the attention, memory, and copy subtests was confirmed with Spearman
      rank correlation coefficient. Each MMSE subtest was significantly related to a
      parallel neuropsychological test. We measured divergent validity by testing the
      difference between the MMSE subtest correlation with its parallel
      neuropsychological test and its nonparallel neuropsychological test. The MMSE
      subtests of attention and memory showed similar relationships with their parallel
      neuropsychological tests as they did with nonparallel neuropsychological tests of
      attention, memory, and naming. These 2 subtests, however, did show divergence
      from a neuropsychological test of copy, most likely indicating that these 2 MMSE
      subtests are measuring the verbal (and not the performance) domain. The MMSE
      subtest of copy showed the poorest convergent and divergent validity.
      CONCLUSIONS: The 3 subtests did not show sufficient divergent validity to warrant
      a conclusion of their domain specificity. Thus, when a more detailed diagnostic
      profile is required, a thorough neuropsychological evaluation will provide a more
      valid description of an individual's cognitive profile.

PMID- 9193207
TI  - Selective cortical and hippocampal volume correlates of Mattis Dementia Rating
      Scale in Alzheimer disease.
AB  - OBJECTIVE: To examine whether each of the 5 Mattis Dementia Rating Scale (DRS)
      scores related to magnetic resonance imaging-derived volumes of specific cortical
      or limbic brain regions in patients with Alzheimer disease (AD). DESIGN:
      Relations between DRS measures and regional brain volume measures were tested
      with bivariate and multivariate regression analyses. SETTING: The Aging Clinical
      Research Center of the Stanford (Calif) University Department of Psychiatry and
      Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the
      Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. PATIENTS AND
      OTHER PARTICIPANTS: Fifty patients with possible or probable AD. Magnetic
      resonance imaging data from 136 healthy control participants, age 20 to 84 years,
      were used to correct brain volumes for normal variation arising from intracranial
      volume and age. MAIN OUTCOME MEASURES: The DRS scores and volumes of regional
      cortical gray matter and of the hippocampus. RESULTS: Memory scores of the
      patients with AD were selectively related to hippocampal volumes. Attention and
      construction scores were related to several anterior brain volume measures, with
      attention showing a significantly greater association to right than left
      hemisphere measures. Initiation/perseveration scores were not significantly
      correlated with any measure of regional gray matter volume, but performance was
      related to prefrontal sulcal widening, with a greater association with the left
      than right sulcal volume. CONCLUSIONS: Certain DRS subtests are predictably
      correlated with selective regional brain volumes in AD. The specific relation
      between memory and hippocampal volumes and the nonsignificant relations between
      memory and regional cortical volumes suggest a dissociation between cortical and
      hippocampal contributions to explicit memory performance.

PMID- 9193208
TI  - Relationship of the antispasticity effect of tizanidine to plasma concentration
      in patients with multiple sclerosis.
AB  - BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and many
      patients do not achieve a satisfactory response to currently available oral
      antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist,
      has been shown to have an antispasticity effect in single center trials of
      patients with MS. OBJECTIVE: To compare plasma concentrations of tizanidine with
      objective measures of muscle tone in patients with MS with moderate to severe
      spasticity. SETTING: Ten centers, all tertiary referral centers for the
      specialized treatment of patients with MS, in the United States and Canada.
      DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of
      tizanidine hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients
      with spastic MS who were not taking any interfering medication, such as an
      antispasticity drug or other alpha-noradrenergic agonist, entered the trial.
      RESULTS: Tizanidine treatment reduced muscle tone significantly, as shown by
      improved Ashworth scores and increased knee swing amplitude recorded by the
      pendulum test, both of which correlated significantly with plasma concentration.
      Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry
      mouth, and fatigue were reported most often in the group treated with tizanidine
      at peak plasma concentration. CONCLUSIONS: Tizanidine reduces spasticity in MS,
      and both therapeutic effects and side effects are related to the plasma drug
      levels.

PMID- 9193210
TI  - Buspirone, a 5-hydroxytryptamine1A agonist, is active in cerebellar ataxia.
      Results of a double-blind drug placebo study in patients with cerebellar cortical
      atrophy.
AB  - OBJECTIVE: To establish the antiataxic effect of buspirone hydrochloride, a
      serotonergic 5-hydroxytryptamine1A (5-HT1A) agonist, in a homogenous group of
      patients characterized by the same well-defined single condition, cerebellar
      cortical atrophy. SETTING: University ataxia research center. METHODS: Double
      blind randomized study of buspirone vs placebo during a 4-month period. PATIENTS:
      Nineteen patients met the inclusion criteria; all completed the study. Of these
      19 patients, 9 were treated with placebo and 10 were treated with the drug. MAIN
      OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural")
      cerebellar functions; quantitative clinical measurements measuring time in
      standard tests that evaluated stance, speech, writing, and drawing; and
      posturographic analysis of the sway path and sway area of the center-of-foot
      pressure. The primary end point was improvement of the posttherapeutic change of
      one of the semiquantitative ataxic scores. The secondary end points were
      modification of the changes of quantitative measures--clinical or posturographic.
      RESULTS: In intention-to-treat analysis, a significant improvement of the primary
      end point, ie, the posttherapeutic change of the ataxic kinetic score, was shown.
      Among secondary end points, the maximum time of standing with feet together also
      was significantly improved. CONCLUSIONS: Buspirone is active in cerebellar ataxia
      of patients with cerebellar atrophy. These results confirm the data suggested by
      open-label studies with buspirone. However, the effect is partial and not
      clinically major. These pharmacological results might be due to serotonergic
      mechanisms and confirm a possible link between cerebellar ataxia and the
      metabolism of serotonin.

PMID- 9193209
TI  - Cerebral hemispheric lateralization in cardiac autonomic control.
AB  - OBJECTIVE: To identify cerebral hemispheric lateralization in cardiac autonomic
      control. PATIENTS: Eight patients undergoing an intracarotid amobarbital sodium
      test as a presurgical evaluation of temporal lobe epilepsy. DESIGN: Power
      spectral analysis of heart rate variability before and after intracarotid
      amobarbital injection. SETTING: University hospital and research center. MAIN
      OUTCOME MEASURE: The changes in the ratio of low-frequency (LF) (sympathetic) to
      high-frequency (HF) (parasympathetic) power (LF/HF ratio), a measure of
      sympathovagal balance, after hemispheric inactivation. RESULTS: The LF/HF ratio
      changed as follows: right preinactivation = 3.81 +/- 0.96, postinactivation =
      3.40 +/- 1.23; left preinactivation = 2.74 +/- 0.49, postinactivation = 4.34 +/-
      0.59 (mean +/- SEM). The test of interaction between laterality and inactivation
      using a 2-way repeated-measures analysis of variance was statistically
      significant (P = .001). The increased ratio on the left side (1.61 +/- 0.70) was
      statistically significant (P = .03), but the decrease on the right side (-0.40 +/
      0.46) was not (P < or = .70). CONCLUSIONS: These findings suggest that there is
      a cerebral lateralization in cardiac autonomic control and that the right
      cerebral hemisphere predominantly modulates sympathetic activity. This study may
      help identify subgroups of patients with intracranial disease at high risk of
      cardiac complications.

PMID- 9193211
TI  - The validity of new memory complaints in the elderly.
AB  - OBJECTIVE: To determine the validity of new subjective memory complaints (MCs)
      from individuals who previously, when without dementia, denied having MCs.
      DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging
      and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly
      individuals who were part of a registry for the study of conditions related to
      aging in North Manhattan, NY. Patients were selected if they were initially
      without dementia and had completed at least 2 successive annual clinical and
      neuropsychological evaluations and provided their own medical history. MAIN
      OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding
      Test and a visual memory task--and global performance on a neuropsychological
      test battery and clinical evaluation, by which questionable dementia or dementia
      was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects
      with MCs at the initial evaluation performed no worse on the memory test than the
      80 subjects who denied MCs initially. There was a weak association between MCs
      and the diagnosis of questionable dementia at baseline (P = .04), but this was
      nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of
      the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these
      21 subjects performed significantly worse on the memory tests, were 5 times more
      likely to have significant cognitive impairment, and had shown significantly
      greater decline over the preceding year on several of the cognitive measures than
      the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when
      without dementia recently denied MCs, may suggest the presence of significant
      impairment of memory or cognition.

PMID- 9193212
TI  - Dietary antioxidants and Parkinson disease. The Rotterdam Study.
AB  - OBJECTIVE: To investigate whether high dietary intake of antioxidants decreases
      the risk of Parkinson disease (PD). SETTING: The community-based Rotterdam Study,
      the Netherlands. DESIGN: The cross-sectional study formed part of a large
      community-based study in which all participants were individually screened for
      parkinsonism and were administered a semiquantitative food frequency
      questionnaire. The study population consisted of 5342 independently living
      individuals without dementia between 55 and 95 years of age, including 31
      participants with PD (Hoehn-Yahr stages 1-3). RESULTS: The odds ratio for PD was
      0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E
      intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4
      1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids
      intake, all adjusted for age, sex, smoking habits, and energy intake. The
      association with vitamin E intake was dose dependent (P for trend = .03). To
      assess whether the association was different in participants with more advanced
      disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This
      did not fundamentally alter the results. CONCLUSION: Our data suggest that a high
      intake of dietary vitamin E may protect against the occurrence of PD.

PMID- 9193213
TI  - Changing interpretations of the human cortical pattern.
AB  - There has been a long historical succession of scientific description of the
      cerebral cortex, usually accompanied by conflicting speculations on its function.
      It was noted by Thomas S. Kuhn that scientific descriptions are phrased in terms
      of the prevailing scientific paradigm and that disagreement about the
      interpretation of observed phenomena is what drives scientists to formulate new
      theories. The objectives of this study were to examine how the observation of
      Kuhn can help to gain insight into historical concepts of brain functioning from
      contemporary descriptions of the cortical gyrations, to examine how these
      historical concepts are relevant to neurology today, and to demonstrate how
      subjective these concepts are because they are based on interpretations that may
      be wrong. The method used here is examination of historical sources that give
      descriptions and illustrations of the cerebral cortex and contemporary theories
      of brain function. I have found that the emphases on cortical description have
      varied according to the prevailing contemporary paradigm. Debates about and
      between different paradigms mirror some themes in current neuroscience. In
      conclusion, the observations of Kuhn help to interpret descriptions to shed light
      on theories of cerebral cortical functioning, and they demonstrate that a
      scientific description is necessarily highly subjective (since it is phrased in
      terms of the current paradigm). The insights that can be gained are relevant to
      modern neurology and neuroscience research.

PMID- 9193214
TI  - Facial beauty. Myth or reality?

PMID- 9193215
TI  - Inherited nonsyndromic hearing loss. An audiovestibular study in a large family
      with autosomal dominant progressive hearing loss related to DFNA2.
AB  - OBJECTIVE: To study nonsyndromic progressive sensorineural hearing loss (SNHL)
      with significant linkage to the DFNA2 locus on chromosome 1p in a Dutch kindred.
      DESIGN: A 6-generation family with 194 family members was studied. Of the
      presumably affected persons, 43 were examined in detail to obtain audiograms and
      37 underwent vestibulo-ocular examination. RESULTS: Regression analysis showed
      significant and equal linear progression in SNHL with age (by about 1 dB per
      year) at all frequencies. Offset values were close to zero at the low frequencies
      (0.25, 0.5, and 1 kHz) but increased systematically with the frequency. It is
      likely that they represent congenital high-frequency SNHL: about 15 dB at 2 kHz,
      30 dB at 4 kHz, and 50 dB at 8 kHz. Bilateral caloric weakness was not observed.
      A significant finding was that 25% to 35% (depending on the exclusion criteria)
      of the patients showed an increased vestibulo-ocular reflex (hyperreactivity) as
      measured by rotatory responses. Forty-one patients showed significant linkage to
      the 1p locus. CONCLUSIONS: Including the present family, 4 families have been
      reported to show linkage to chromosome 1p. Statistical analysis of the
      audiological data shows a progression of 1 dB per octave per year in this type of
      progressive SNHL.

PMID- 9193216
TI  - Porous high-density polyethylene implants in auricular reconstruction.
AB  - OBJECTIVE: To evaluate the ability of porous high-density polyethylene (Medpor)
      implants to tolerate exposure and support skin grafts when used to reconstruct
      defects in auricular cartilage in an animal model. DESIGN: Polyethylene implants
      placed in surgically created defects in auricular cartilage and covered with a
      skin flap were then exposed at either 4, 7, or 21 days after implantation. The
      exposed implants were then allowed to heal secondarily or received a skin graft 1
      week later. The ability of polyethylene implants to tolerate exposure and support
      skin grafts was observed clinically and via histological study of the
      implantation sites. SUBJECTS: Nine adult New Zealand rabbits. RESULTS:
      Polyethylene implants demonstrated excellent ability to tolerate wound exposure
      as early as 4 days after implantation, with extrusion of 1 of the 36 implants
      placed. The degree of secondary wound healing increased as the interval from
      implantation to exposure increased from 4 to 21 days. Exposed polyethylene
      implants in all groups also supported all 18 skin grafts placed 1 week after
      exposure of the implant surface. CONCLUSIONS: Polyethylene implants are well
      tolerated as replacements for native cartilage in auricular reconstruction.
      Polyethylene implants tolerated wound exposure as early as 4 days after
      implantation and demonstrated the ability to heal by secondary intention and
      support skin grafts. This is likely because of the extent of fibrovascular
      ingrowth from surrounding tissue, which allows the material to behave more like
      native tissue and less like a foreign body in this setting.

PMID- 9193217
TI  - Shrapnell membrane and mastoid pneumatization.
AB  - OBJECTIVE: To assess whether a correlation exists between the degree of pars
      flaccida (PF) retraction and the degree of mastoid pneumatization. DESIGN: The
      degree of PF retraction was defined by means of an operating microscope and a
      pneumatic otoscope. Degree of mastoid pneumatization was assessed
      planimetrically, using mastoid x-rays. SETTING: Private otologic clinic.
      PARTICIPANTS: A total of 595 ears, with intact pars tensa, of 332 adult patients.
      RESULTS: The degree of PF retraction was found to be inversely correlated to the
      level of mastoid pneumatization. Poorly pneumatized mastoids were associated with
      PF retractions. The poorer the pneumatization, the deeper the retraction. Well
      pneumatized mastoids were associated with normal position of the PF. CONCLUSIONS:
      This study lends further support to the possibility that the mastoid pneumatic
      system functions as a middle ear pressure buffer. This possibility gives further
      explanation as to why ears with poorly pneumatized mastoids tend to develop
      tympanic membrane retractions and perforations, incus necrosis, or retraction
      pocket cholesteatoma, while ears with a large pneumatic system are rarely at such
      risk.

PMID- 9193218
TI  - Rapid clinical evaluation of anosmia. The alcohol sniff test.
AB  - BACKGROUND: Smell impairment affects 1% to 2% of Americans and leads to frequent
      physician visits. Olfactory testing is available in chemosensory centers, but not
      as part of a routine cranial nerve examination. The alcohol sniff test (AST),
      which uses the standard 70% isopropyl alcohol pad, was developed as a quick,
      reliable measure of olfactory function. METHODS: Sixty-four patients and 36
      healthy control subjects (N = 100) were tested with the AST and with a standard
      butanol threshold test. RESULTS: The AST reliably, consistently, and correctly
      measured olfactory function. CONCLUSIONS: The AST is a rapid, reliable olfactory
      test that can be used for screening olfactory function and should be incorporated
      in the routine cranial nerve examination.

PMID- 9193220
TI  - Clinical significance of asymptomatic sinus abnormalities on magnetic resonance
      imaging.
AB  - OBJECTIVE: To investigate the prevalence of abnormalities of the paranasal sinus
      detected by magnetic resonance imaging (MRI) in asymptomatic subjects. DESIGN:
      Prospective study. SETTING: Outpatient clinic. PATIENTS: A total of 325 patients
      who underwent MRI for suspected intracranial disease. Of those, 257 patients
      lacked nasal or sinus symptoms. RESULTS: Sinus abnormalities were seen on MRI in
      153 (47.1%) of 325 patients, including 107 (41.6%) of the 257 asymptomatic
      patients. Subjects older than 50 years had a significantly higher frequency of
      sinus abnormalities on MRI (49.8%) vs those younger than 50 years (39.5%) (P <
      .05). The maxillary sinus abnormality was observed in 99 patients (38.5%) and the
      ethmoid sinus abnormality was observed in 52 (20.2%) (P < .01). The most common
      abnormality was mucosal thickening in the maxillary and ethmoid sinuses.
      CONCLUSION: A high prevalence of sinus abnormalities was detected in asymptomatic
      subjects on MRI.

PMID- 9193219
TI  - Glucocorticoid treatment for nasal polyps. The use of topical budesonide powder,
      intramuscular betamethasone, and surgical treatment.
AB  - BACKGROUND: The treatment of nasal polyps is controversial, and medical treatment
      alone has been little investigated to our knowledge. OBJECTIVE: To examine the
      efficacy of therapy using only topical budesonide powder and topical budesonide
      powder supplemented with surgical removal or intramuscular betamethasone. DESIGN:
      Randomized, double-blind comparison of 2 dosages and additional treatment, if
      therapy failed. After 1 year, treatment with medication was stopped, and the
      demand for renewed treatment was monitored for another year. PATIENTS: Patients
      with bilateral nasal polyps who demanded treatment were consecutively enrolled in
      a hospital outpatient clinic or specialty private practice. During a 15-month
      period from 1990 to 1992, a total of 126 patients entered the 2-year study.
      INTERVENTIONS: In phase 1, randomized and double-blind treatment with a topical
      medication, budesonide powder, 800 micrograms or 400 micrograms daily, or a
      placebo was given for 1 month. In phase 2, randomized and double-blind treatment
      with budesonide powder, 800 micrograms or 400 micrograms daily, was given. At the
      end of phase 1, failed therapy was supplemented by randomly assigned treatment of
      either surgical removal or a single injection of sustained released
      betamethasone. In phase 3, treatment with the medication was discontinued, and
      patients were monitored for another year. The time when treatment was required
      again was noted. The present article deals with phases 2 and 3. MAIN OUTCOME
      MEASURES: Patients' scores of treatment efficacy as well as symptoms and signs.
      Semiquantitative measurement of sense of smell and calculation of peak expiratory
      flow rate index based on nasal and oral peak expiratory flow. RESULTS: In all
      outcome measures, a comparison of the data before treatment with the
      corresponding figures during phase 2 showed statistically significant efficacy.
      The clinical course was described at the end of phase 2. About 85% of the
      patients, including those who received additional therapy because the initial
      therapy failed, rated total or substantial control over the symptoms. The 2
      dosages investigated showed equal results. These findings were consistent with
      the signs recorded and the peak expiratory flow rate index. The results of phase
      3 showed that 50% of patients had demanded treatment after 4 months, while 34%
      managed without medication after 1 year. CONCLUSIONS: The clinical course in this
      study showed that most patients with nasal polyps do well with medical treatment.
      Therefore, surgery was required in few patients. However, the potential of
      medical treatment should be further explored in future studies.

PMID- 9193221
TI  - p53 mutation as a prognostic marker in advanced laryngeal carcinoma. Department
      of Veterans Affairs Laryngeal Cancer Cooperative Study Group.
AB  - OBJECTIVE: To determine the relationship of p53 mutations in advanced laryngeal
      carcinomas to p53 immunohistochemistry, organ preservation, and patient survival.
      DESIGN: Paraffin-embedded tumor specimens were obtained from patients enrolled in
      the Department of Veterans Affairs Laryngeal Cancer Cooperative Study, a multi
      institutional randomized clinical trial comparing induction chemotherapy
      (cisplatin and fluorouracil) plus radiation therapy surgery plus postoperative
      radiation therapy. Tumor specimens were analyzed for p53 mutations in exons 5
      through 8 by using single-strand conformational polymorphism (SSCP) analysis
      followed by DNA sequencing of all variants. Five-year follow-up data were
      available for all patients studied. SUBJECTS: Forty-four patients enrolled in the
      Department of Veterans Affairs Laryngeal Cancer Cooperative Study from whom
      paraffin-embedded tumor specimens were readily available. RESULTS: p53
      immunostaining did not correlate with p53 SSCP and DNA sequencing results. More
      than half (62% [16/26]) of the tumors that overexpressed p53
      immunohistochemically did not have a detectable p53 gene mutation. Similarly, 39%
      (7/18) of tumors that did not overexpress p53 did have a p53 gene mutation. p53
      mutations were present in 39% of tumors tested. Mutations within exon 5 made up
      41% of p53 gene mutations in laryngeal carcinomas. Transitions were the most
      common type of mutation in this study (92% of mutations). CONCLUSIONS: The
      presence of a p53 mutation as detected by SSCP is associated with decreased
      patient survival. Further study is required to confirm this relationship and to
      determine whether specific p53 mutations predict organ preservation.

PMID- 9193222
TI  - Frequent loss of heterozygosity on chromosome arm 18q in squamous cell
      carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.
AB  - OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q
      in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain
      reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2
      tumors) and blood samples from 17 patients with head and neck squamous cell
      carcinoma was performed using primers flanking 16 microsatellite repeat
      polymorphisms spanning most of chromosome 18q. DNA was extracted only from
      specimens with greater than 70% tumor nuclei. SETTING: Research university.
      PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN
      OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more
      than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative
      markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%)
      of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal
      region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without
      proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors
      defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on
      chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH
      in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1
      q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be
      more than one 18q tumor suppressor gene involved in the genesis and progression
      of head and neck squamous cell carcinomas.

PMID- 9193223
TI  - Prognostic significance of nucleolar organizer regions in adenoid cystic
      carcinomas of the head and neck.
AB  - OBJECTIVE: To determine the prognostic use of nucleolar organizing region (AgNOR)
      counts and clinical and histopathological features in adenoid cystic carcinoma.
      DESIGN: Argyrophilic staining was applied to ordinary formalin-fixed, paraffin
      embedded specimens and evaluated to obtain the mean number of AgNORs and the
      percentage of nuclei with more than 1 (pAgNOR > 1), more than 2, more than 3, and
      more than 4 AgNORs. RESULTS: Using the log rank test, the mean AgNOR count showed
      no correlation with the disease-free period. All pAgNOR parameters exceeding the
      respective overall mean had poorer prognosis when compared with those below the
      mean (P = .02). The pAgNOR > 1 appeared as the best discriminator, singling out
      all treatment failures (P < or = .001). This parameter also showed a high degree
      of intraobserver and interobserver reproducibility. Stage of the disease,
      violated resection margins, and presence of the histopathological solid subtype
      were markers of an unfavorable prognosis. Multivariate analysis by the Cox model
      showed that pAgNOR > 1 (P < or = .001) and tumor stage (P = .03) were the only
      statistically significant parameters. CONCLUSIONS: Estimation of pAgNOR > 1 is
      easy, quick, and highly reproducible. It may become a useful prognostic parameter
      in adenoid cystic carcinoma, but larger studies should be performed to confirm
      the reliability of this method.

PMID- 9193224
TI  - Neurilemomas of the parapharyngeal space.
AB  - OBJECTIVE: To review the surgical management of neurilemomas of the
      parapharyngeal space (PPS). DESIGN: Retrospective survey of the clinical
      presentation, radiological features, surgical approaches, surgical findings, and
      postoperative neurological sequelae of neurilemomas of the PPS. SETTING: Academic
      tertiary care head and neck referral center. PATIENTS: Fourteen patients with
      neurilemomas of the PPS, 12 were in the poststyloid compartment. INTERVENTIONS:
      Preoperative evaluation with computed tomography and/or magnetic resonance
      imaging with or without angiography. Surgical resection was performed through a
      transcervical approach. MAIN OUTCOME MEASURES: Radiological features, adequacy of
      surgical approach, and neurological sequelae of surgery. RESULTS: Radiological
      studies could distinguish prestyloid from poststyloid tumors and, with
      poststyloid tumors, can usually differentiate between glomus tumor and
      neurilemoma. The transcervical approach permitted adequate surgical access. Five
      of the tumors in the poststyloid space were neurilomomas originating from the
      sympathetic nervous system, and all 5 patients with these tumors developed Horner
      syndrome postoperatively. CONCLUSIONS: Computed tomographic and/or magnetic
      resonance studies should be routinely obtained to evaluate tumors of the PPS, but
      angiography is indicated only in selected cases. Both prestyloid and poststyloid
      neurilemomas can be resected through a transcervical approach. Resection of
      neurilemomas has an attendant risk for neurological dysfunction.

PMID- 9193225
TI  - Maturational descent of the epiglottis.
AB  - BACKGROUND: Otolaryngologists and anesthesiologists have described a maturational
      descent of the epiglottis that occurs in infancy and childhood. OBJECTIVE: To
      investigate the changing level of the epiglottis to confirm and characterize this
      phenomenon more completely. DESIGN: A survey of 500 images with 338 images
      selected for the study. SETTINGS: A tertiary care facility. PATIENTS:
      Asymptomatic children aged 1 day to 18 years. MAIN OUTCOME MEASURE: The position
      of the tip of the epiglottis was correlated with the cervical vertebral level.
      RESULTS: Data indicate that maturational descent of the epiglottis starts in
      infancy and continues into adolescence. These results are statistically
      significant (P < .01). CONCLUSION: Maturational descent of the epiglottis occurs
      in a predictable pattern. Understanding this phenomenon may facilitate
      laryngoscopic, as well as clinical and radiologic, evaluation of the airway in
      children.

PMID- 9193226
TI  - Peritonsillar abscess in early childhood. Presentation and management.
AB  - OBJECTIVE: To highlight the modes of presentation and management of a
      peritonsillar abscess in children younger than 5 years. DESIGN: Retrospective
      case series. SETTING: Tertiary referral pediatric otolaryngology practice.
      PATIENTS: Seven children younger than 5 years. RESULTS: The mean age of the
      children studied was 27 months (age range, 7-41 months). Five (71%) of the 7
      patients underwent computed tomographic scanning to confirm the diagnosis. Pus
      was cultured at surgery in every case. The most common organism detected was
      Streptococcus viridans. The average hospital stay was 72 hours (range, 22 hours
      to 12 days). After diagnosis of an abscess, all patients underwent an
      electrocautery tonsillectomy and had an uneventful recovery. CONCLUSIONS:
      Children younger than 5 years who present with poor oral intake, high fever,
      drooling, and trismus should be suspected of having a peritonsillar abscess. A
      computed tomographic scan of the neck is usually required to confirm a suspected
      diagnosis. Prompt diagnosis and treatment will lead to a considerable decrease in
      morbidity. Immediate tonsillectomy is a safe and effective means of abscess
      drainage.

PMID- 9193227
TI  - Cervicofacial necrotizing fasciitis. A devastating complication of
      blepharoplasty.
AB  - We report a case of cervicofacial necrotizing fasciitis that developed after
      blepharoplasty, an occurrence that, to our knowledge, has not previously been
      reported in the medical literature. A patient who presented to our institution 3
      days after undergoing blepharoplasty of the upper eyelid was diagnosed as having
      fulminant fasciitis involving extensive areas of the face, scalp, and neck. We
      review the case in detail and discuss clinical and radiological clues to
      diagnosis, surgical and medical management, wound care, and subsequent scar
      contracture. This case emphasizes the need for individualized, appropriate
      postoperative care and for an awareness of this rare, potentially fatal
      complication. Early recognition and aggressive treatment of cervicofacial
      fasciitis can arrest its rapid progression and prevent devastating sequelae.

PMID- 9193228
TI  - Lymphoepithelial carcinoma of the minor salivary gland.
AB  - Undifferentiated carcinoma of the minor salivary glands has been rarely reported
      in the world literature. Lymphoepithelial carcinoma, which is a variant of
      undifferentiated carcinoma, is distinguished from small cell and large cell
      undifferentiated carcinoma by its association with benign lymphoepithelial
      lesions. We report a case of a lymphoepithelial carcinoma developing in a minor
      salivary gland of the oral cavity in a 69-year-old woman. To our knowledge, this
      is the first reported case of a lymphoepithelial carcinoma arising from a minor
      salivary gland.

PMID- 9193229
TI  - Airway management of neonates with antenatally detected head and neck anomalies.
AB  - Five cases of prenatally detected neck masses that had a potential for airway
      obstruction at birth are described. The various options for management of the
      airway are discussed, including using maternal-fetal circulation until
      intubation, rigid bronchoscopy, tracheotomy, cyst aspiration, or extracorporeal
      membrane oxygen support. Congenital abnormalities involving the fetal face or
      neck are extremely rare. With technical advances in ultrasonography, these masses
      were first noted on prenatal ultrasound in the late 1970s. Before that period,
      they were detected at delivery. These masses are solid or cystic and may cause
      asphyxia because of airway obstruction at the time of delivery. The survivability
      of these neonates without immediate intervention at birth is 0% to 20%. If a neck
      mass is detected in the fetus by prenatal ultrasonography, then a strategic plan
      for these types of cases should be developed early in the prenatal period. The
      airway management plan should be tailored for each individual case. Coordination
      and the expertise of an obstetrician, neonatologist, anesthesiologist, and
      pediatric otolaryngologist are needed to manage these complex situations.

PMID- 9193230
TI  - Pressure-induced ocular torsion.
AB  - We describe 3 patients within whom ocular torsion could be induced by application
      of positive air pressure to one external ear canal. In all cases, the superior
      pole of the eye rotated away from the stimulated ear when positive pressure was
      applied. The amplitude of torsion ranged from 3 degrees to 16 degrees.
      Exploratory tympanotomy was performed in all 3 patients. In 2 patients, round
      window fistulas were found and repaired. In the third patient, no fistula was
      noted but the oval- and round-window areas were patched. There was no resolution
      of symptoms after surgery in any patient. Based on these cases, patients
      presenting with pressure-induced ocular torsion are unlikely to have resolution
      of their symptoms, even when a perilymphatic fistula is confirmed and repaired.
      We hypothesize that pressure-induced ocular torsion is caused by an irreversible
      juxtaposition of the utricle and stapes footplate.

PMID- 9193231
TI  - Multicentric eighth cranial nerve schwannoma.
AB  - To our knowledge, only 3 histopathologically proved cases of multicentric eighth
      cranial nerve schwannoma have been described in the literature since 1981. We
      describe a patient with 2 isolated eighth cranial nerve schwannomas arising
      separately from the left cochlea and internal auditory canal. These 2 tumors were
      diagnosed using magnetic resonance imaging prior to resection, and the diagnosis
      was further confirmed by intraoperative findings and histopathologic analysis.
      The genetic molecular basis and clinical features of this rare tumor have been
      overlooked. The value of the transotic approach for total tumor removal is
      emphasized.

PMID- 9193232
TI  - Pathologic quiz case 1. Malignant peripheral nerve sheath tumor of the ethmoidal
      sinus.

PMID- 9193233
TI  - Pathologic quiz case 2. Congenital cartilaginous rests of the neck (CCRNs)
      (wattles).

PMID- 9193234
TI  - The pacifier thermometer. Will it be useful?

PMID- 9193235
TI  - Does greater pediatric experience influence treatment choices in chronic disease
      management? Dialysis modality choice for children with end-stage renal disease.
AB  - OBJECTIVE: To determine whether treatment choice for children with end-stage
      renal disease varies with greater pediatric experience at the dialysis facility.
      DESIGN: National cross-sectional study. SETTING: Outpatient dialysis facilities
      throughout the United States. PATIENTS: All children (age, < or = 19 years)
      undergoing dialysis in 1990, identified using the Medicare End-stage Renal
      Disease registry (1990 facility survey and quarterly dialysis records). OUTCOME
      MEASURES: The odds of receiving peritoneal dialysis vs hemodialysis according to
      the pediatric experience of the facility. "Pediatric experience" for dialysis
      facilities was defined as the number of patients 19 years old or younger divided
      by the total number of patients treated at that facility. Adjustment, using
      multiple logistic regression, was made for differences in age, sex, cause and
      duration of end-stage renal disease, income, education, and facility
      characteristics. RESULTS: In 1990, there were 1256 patients 19 years old or
      younger who underwent a single-treatment modality at a single facility for most
      of the year. Sixty-three percent (790/ 1256) were treated at facilities with
      fewer than 5% of patients younger than 19 years. Thirty-six percent were treated
      at centers with less than 1% of pediatric patients. In a multivariate analysis,
      pediatric experience in a facility was independently associated with the use of
      peritoneal dialysis in children. Children treated at facilities with more than
      10% pediatric patients were 60% more likely to be treated with peritoneal
      dialysis rather than hemodialysis compared with children treated at facilities
      with fewer than 1% of pediatric patients, even after controlling for patient age,
      race, income, education, cause and duration of end-stage renal disease, and
      facility characteristics such as hospital-based vs independent unit and for
      profit vs not-for-profit status (odds ratio, 1.6; 95% confidence interval, 1.1
      2.3). CONCLUSIONS: Children receiving care at dialysis facilities that have
      greater experience with pediatric patients are more likely to receive peritoneal
      dialysis than hemodialysis, a therapy with recognized clinical benefits for
      children that is inherently less resource intensive than is hemodialysis.

PMID- 9193236
TI  - The pacifier thermometer. Comparison of supralingual with rectal temperatures in
      infants and young children.
AB  - OBJECTIVE: To determine the correlation between supralingual temperatures
      obtained with a new electronic pacifier thermometer (Steridyne) and rectal
      temperatures obtained with a digital electronic thermometer. DESIGN: Prospective
      study. SETTING: Pediatric emergency department and pediatric inpatient ward of a
      tertiary university hospital. PARTICIPANTS: Convenience sample of 100 patients,
      aged 7 days to 24 months. MAIN OUTCOME MEASURES: A supralingual and rectal
      temperature were obtained for each patient. For the first 30 patients, the time
      needed for the pacifier thermometer to signal a final, steady-state reading was
      recorded. RESULTS: The mean +/- SD difference between rectal temperatures and
      supralingual temperatures adjusted upward by 0.5 degree F was -0.01 degree F +/-
      0.42 degree F (statistically zero) (95% confidence interval, -0.09 degree F to
      0.07 degree F). The correlation coefficient between supralingual and rectal
      temperatures was 0.95. Sensitivity and specificity of the pacifier thermometer
      for detecting fever (temperature > or = 100.4 degrees F [> or = 38.0 degrees C])
      was 72.0% and 98.0%, respectively (positive predictive value, 97.3%; negative
      predictive value, 77.8%). Increasing supralingual temperatures by 0.5 degree F
      increased sensitivity to 92.0%, and decreased specificity to 76.0% (positive
      predictive value, 79.3%; negative predictive value, 90.5%). It took an average
      time of 3 minutes 23 seconds for the pacifier thermometer to display a steady
      state temperature. CONCLUSIONS: The pacifier thermometer evaluated here was found
      to be an accurate means of temperature measurement when recorded temperatures
      were adjusted upward by 0.5 degree F. The approximate 3 minutes required for a
      final temperature determination makes the pacifier thermometer most appropriate
      for use in low-volume ambulatory care settings and in the home. Further
      investigation of this device is recommended.

PMID- 9193237
TI  - Fears and other suspected risk factors for carrying lethal weapons among urban
      youths of middle-school age.
AB  - OBJECTIVE: To estimate the strength of a suspected causal association between
      fearfulness and carrying a lethal weapon among urban middle-school students,
      while holding constant other suspected risk factors. DESIGN: A prospective study
      of an epidemiological sample assessed at baseline in 1992 and 1 year later, with
      relative risk estimates derived from the conditional form of the multiple
      logistic regression model used to hold constant alternative explanatory
      variables. SETTING: An urban environment in the mid-Atlantic region of the United
      States. PARTICIPANTS: An epidemiological sample of 1131 youths enrolled in public
      middle schools. MAIN OUTCOME MEASURES: Carrying a lethal weapon for protection or
      defense during a 1-year observation interval after the baseline assessment of
      fears and other suspected risk factors. RESULTS: Of the 1131 youths, 194 (17%)
      reported carrying a lethal weapon for protection or defense during the 1-year
      interval of follow-up observation after baseline; 937 youths (83%) reported that
      they had not carried a lethal weapon for any reason. Self-reported fears, deviant
      peer affiliation, and worrying were associated with risk of starting to carry a
      weapon. For youths with the lowest worrying scores, the lowest neighborhood
      danger scores, and the least affiliation with deviant peers, self-reported fears
      were associated with risk of starting to carry a lethal weapon (relative risk
      estimate, 1.68; 95% confidence interval, 1.11-2.52; P = .01), even after holding
      constant age, sex, and conduct problems. However, the fear of crowded or closed
      in places and the fear of leaving home alone were more salient risk factors than
      the fear of using public transportation or the fear of open spaces. CONCLUSIONS:
      In this study, youths with fears were at greater risk of carrying a lethal weapon
      for protection or defense, even when alternative explanatory variables were taken
      into account. Pending confirmation by other investigators, this new finding could
      point out a useful target for public health interventions to reduce the carrying
      of weapons and associated violence in urban America.

PMID- 9193238
TI  - State-to-state variations in newborn screening policies.
AB  - BACKGROUND: Population-based newborn screening for genetic and metabolic
      disorders is standard practice in all states in the United States. Policies
      governing newborn screening are determined at the state level; however, and thus,
      a great degree of variability exists between states regarding many facets of such
      screening. OBJECTIVE: To gather information relating to the processes, content,
      and outcomes of policy making affecting newborn screening programs across the
      United States. METHODS: We surveyed the directors of newborn screening programs
      for each of the 50 states using a postal questionnaire. The questionnaire
      solicited information about the specific tests incorporated in each state's panel
      of screening tests and information pertaining to the policy-making processes by
      which decisions are reached regarding this testing. RESULTS: Substantial
      variation exists across states regarding both the processes of policy formulation
      and the outcomes of decisions made about newborn screening. All states currently
      screen for phenylketonuria and congenital hypothyroidism. Extensive variation
      exists across states in testing for other disorders. The processes by which state
      policy makers arrive at decisions in this area are extremely diverse. Almost
      three fourths of the states have standing expert advisory bodies who issue
      recommendations regarding screening program modifications, but the authority
      granted to these panels varies substantially. Some regional cooperation in this
      area exists. CONCLUSIONS: Further development of regional cooperation could offer
      some states greater efficiency in both laboratory testing and screening policy
      formulation. From the standpoint of an individual state. Wisconsin's approach to
      policy development in this area is described as a model worthy of consideration.

PMID- 9193239
TI  - A motor milestone change noted with a change in sleep position.
AB  - OBJECTIVE: To evaluate whether sleeping in the supine position resulted in
      changes in gross or fine motor developmental milestones observed at routinely
      scheduled well-child checkups at 4 or 6 months of age. DESIGN: A retrospective
      chart review. SETTING: One private pediatric practice involving 2 full-time and 2
      part-time board-eligible or board-certified pediatricians. SUBJECTS: The study
      included 343 full-term infants whose weights were appropriate or large for
      gestational age, had no history of hospitalization other than for normal newborn
      care, and were examined in the office for their 4-month well-child checkup within
      2 weeks of being 4 months old. METHODS: The Denver Developmental Screening Test
      Revised was administrated at the 4- and 6-month well-child checkups. The primary
      sleep positions of the infants were determined by telephone survey, office
      interview, or letter after the 6-month checkup was completed. Background data
      collected from the mother for each mother-infant pair included maternal age at
      the time of birth, parity, and marital status, Medicaid status and ethnicity of
      the infant, and whether the infant was breast-fed. RESULTS: Infants who slept in
      the side or supine position were less likely to roll over at the 4-month checkup
      than infants who slept primarily in the prone position (P < .001). No significant
      differences were found when comparison by maternal age, parity, or marital
      status, Medicaid status or ethnicity of the infant, or the use of breast-feeding
      were considered. Other motor milestones screened did not show statistically
      significant changes. CONCLUSIONS: Sleep position significantly influences the age
      of achieving the gross motor developmental milestone of rolling over; infants who
      sleep in the side or supine position roll over later than infants who sleep in
      the prone position.

PMID- 9193241
TI  - Suspended rocking cradles, positional asphyxia, and sudden infant death.
AB  - OBJECTIVE: To describe the risk of unexpected death in infants who are placed in
      suspended rocking cardles. MAIN OUTCOME MEASURES: Ten cases of sudden infant
      death and 5 cases of infant asphyxia with successful resuscitation reported to
      the Consumer Product Safety Commission were analyzed. The death scene
      investigation reports and autopsy material were made available for evaluation.
      All 15 cases implicated a suspended head-to-toe rocking cradle. RESULTS: Infants
      were aged 3 months or younger and were found in the facedown prone position when
      discovered. The cradle was tilted at greater than 5 degrees, and the head was
      wedged at one end of the cradle. A locking pin was not used in 14 cases. Ten of
      the 15 infants died. The autopsy reports listed sudden infant death syndrome as
      the cause of death. CONCLUSIONS: Suspended rocking cradles represent a
      potentially lethal sleeping environment and should not be used without a locking
      pin in place. Infants should be placed in the supine position for sleep.

PMID- 9193240
TI  - Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric
      practice-based survey. Pediatric Practice Research Group.
AB  - OBJECTIVES: To determine the prevalence of symptoms associated with overt
      gastroesophageal reflux (GER) during the first year of life, to describe when
      most infants outgrow these symptoms, and to assess the prevalence of parental
      reports of various symptoms associated with GER and the percentages of infants
      who have been treated for GER. DESIGN: Cross-sectional survey. SETTING: Nineteen
      Pediatric Practice Research Group practices in the Chicago, Ill, area (urban,
      suburban, and semirural). PARTICIPANTS: A total of 948 parents of healthy
      children 13 months old and younger. INTERVENTION: None. MAIN OUTCOME MEASURE:
      Reported frequency of regurgitation. RESULTS: Regurgitation of at least 1 episode
      a day was reported in half of 0- to 3-month-olds. This symptom decreased to 5% at
      10 to 12 months of age (P < .001). Peak reported regurgitation was 67% at 4
      months; the prevalence of symptoms decreased dramatically from 61% to 21% between
      6 and 7 months of age. Infants with at least 4 episodes daily of regurgitation
      showed a similar pattern (P < .001). Peak regurgitation reported as a "problem"
      was most often seen at 6 months (23%); this prevalence decreased to 14% at 7
      months of age. Parental perception that regurgitation was a problem was
      associated with the frequency and volume of regurgitation, increased crying or
      fussiness, reported discomfort with spitting up, and frequent back arching.
      Reported treatment for regurgitation included a change in formula in 8.1%,
      thickened feedings in 2.2%, termination of breast-feeding in 1.1%, and medication
      in 0.2%. CONCLUSIONS: Complaints of regurgitation are common during the first
      year of life, peaking at 4 months of age. Many infants "outgrow" overt GER by 7
      months and most by 1 year. Parents view this symptom as a problem more often than
      medical intervention is given.

PMID- 9193242
TI  - Current positions of graduates of internal medicine-pediatrics training programs.
AB  - OBJECTIVE: To determine what positions graduates of internal medicine-pediatrics
      programs currently hold. DESIGN: A survey of the program directors of residencies
      in internal medicine-pediatrics. PARTICIPANTS: Program directors of the 85
      internal medicine-pediatrics training programs listed in the 1993-1994 Graduate
      Medical Education Directory. MAIN OUTCOME MEASURES: A 1-page survey that
      described the current positions of trainees graduating between 1987 and 1993.
      RESULTS: Seventy-four (87%) of the 85 program directors completed the survey. Of
      the 708 graduates reported on, 68% were practicing as generalists. The
      generalists of this cohort (n = 480) were primarily in private practice settings
      (n = 390, 81%) and most were practicing internal medicine-pediatrics (n = 416,
      85%). Only 12% of the generalists had chosen to practice either pediatrics or
      internal medicine. Twenty-one percent of the total graduates had entered
      subspecialty training. CONCLUSIONS: To our knowledge, the sample of 708 graduates
      is the largest survey of graduates of internal medicine-pediatrics programs to
      date and shows that 68% of graduates are practicing in primary care fields.
      Graduates of internal medicine-pediatrics programs should be considered as an
      important source of primary care physicians.

PMID- 9193244
TI  - Gender differences in physician-patient communication. Evidence from pediatric
      visits.
AB  - OBJECTIVE: To determine whether physician gender and patient gender influence the
      process of communication and parent and child satisfaction during pediatric
      office visits. DESIGN: Content analysis of videotaped pediatric office visits.
      SETTING: University-based pediatric primary care practice. SUBJECTS: Videotaped
      communication between 212 children, ages 4 to 14 years, parents, and physicians.
      Thirty-eight percent were child health supervision visits, and 62% were for the
      management of minor or chronic illnesses. MAIN OUTCOME MEASURES: An established
      coding system of physician-patient communication and measures of parent and child
      satisfaction with medical care. RESULTS: Female physician visits were 29% longer
      than those of male physicians (P < .001). Compared with male physicians, female
      physicians engaged in more social exchange (P < .01), more encouragement and
      reassurance (P < .01), more communication during the physical examination (P <
      .05), and more information gathering (P < .01) with children. Male and female
      physicians engaged in similar amounts of discussions regarding illness
      management. Children were more satisfied with physicians of the same gender (P <
      .05), while parents were more satisfied with female physicians (P < .05).
      CONCLUSIONS: Children communicate more with female than with male physicians and
      show preferences for physicians of the same gender. These findings are consistent
      with communication patterns in adult patients and may have a significant
      influence on gender disparities in health care. Efforts at improving the process
      and outcome of medical care should address gender differences.

PMID- 9193243
TI  - Antecedents of cerebral palsy in a multicenter trial of indomethacin for
      intraventricular hemorrhage.
AB  - OBJECTIVES: To determine if cerebral palsy (CP) rates were lower in the active
      treatment group compared with the control group, as improved survival rates of
      very low-birth-weight infants are postulated to be the cause of the increased
      incidence of CP in preterm infants, to evaluate relationships between multiple
      prenatal, perinatal, and postnatal variables and CP to understand better its
      antecedents in very low-birth-weight infants in the era of surfactant replacement
      therapy, and to determine the usefulness of a cranial ultrasonographic (US) scan
      in predicting CP. DESIGN: Inception cohort follow-up study as part of a
      randomized controlled trial of low-dose indomethacin sodium for the prevention of
      intraventricular hemorrhage. SETTING: Neonatal intensive care units at 3 medical
      centers. PATIENTS: Infants with birth weights between 600 and 1250 g were
      eligible, and 505 infants were enrolled in the original study. Of these infants,
      440 (87%) survived; neurologic examinations were completed on 381 infants (86%)
      at 36 months corrected age. MAIN OUTCOME MEASURES: Statistical analyses were
      performed to identify the antecedents of CP, including the results of frequent
      cranial US scans obtained throughout the newborn period. RESULTS: Cerebral palsy
      was found in 36 (9.5%) of 381 infants at 36 months corrected age (range, 33-39
      months corrected age). Univariate analysis identified chorioamnionitis, treatment
      with surfactant, bronchopulmonary dysplasia, and abnormal cranial US findings as
      antecedents of CP. Periventricular leukomalacia and ventriculomegaly were
      associated with the highest detection rates for CP (37% and 30%, respectively)
      with acceptable false-positive rates. Multivariate analysis identified
      bronchopulmonary dysplasia and an abnormal cranial US scan showing grade 3 to 4
      intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly as
      independent predictors of CP. Odds ratios for the detection of CP using cranial
      US findings tabulated by hospital day were in the range of 7 to 26 beginning on
      day 2. CONCLUSION: The results suggest that cranial US findings are useful
      predictors of CP during a patient's stay in the hospital.

PMID- 9193245
TI  - Pediatric Internet resources. Creation and growth of the PEDINFO index.
AB  - OBJECTIVE: To illustrate the growth of pediatric-related material on the Internet
      as demonstrated by the growth and use of an index of pediatric Internet
      resources. DESIGN: Descriptive analysis. METHODS: The log files of the computer
      systems on which the PEDINFO index was implemented were examined. File size of
      the index was measured, and a record of Internet hosts that connected to the
      server each day was produced. A proportion of Internet sites (n = 300) were
      examined for author reliability and practice enhancement value. RESULTS: In a
      period of 14 months, the file size grew from 7 kilobytes (KB) to more than 80 KB.
      By November 1995, usage exceeded 250 individuals per day and has since then
      leveled off to about 180 users per day. Analysis of the domains of the users
      showed a shift from equal proportion of "com" (commercially obtained Internet
      addresses) and "edu" (educational institution) addresses to an increase in com
      addresses with a stable proportion of edu addresses. One hundred twenty-seven
      sites contained patient or parent information, and 62 sites contained reference
      material. There was a wide range of author reliability ratings. CONCLUSIONS: From
      the growth of PEDINFO, we conclude that an increase in pediatric-related
      information available on the Internet is steady, much of which is patient or
      parent educational material. We anticipate further growth and use of the Internet
      in the exchange of information and cell for further education regarding its use
      so that pediatricians can more easily direct their patients to the most medically
      relevant sources.

PMID- 9193246
TI  - Assessment of the palatability of beta-lactamase-resistant antibiotics in
      children.
AB  - OBJECTIVES: To evaluate the palatability of antibiotics effective against beta
      lactamase-producing bacteria in children and to compare the results obtained with
      those obtained in adults. DESIGN: A taste test of 4 antibiotic suspensions: a
      combination of amoxicillin and clavulanic acid (banana), azithromycin (cherry),
      clarithromycin (wild fruit), and a combination of erythromycin and sulfisoxazole
      (strawberry-banana). SETTING: Outpatient setting. SUBJECTS: A volunteer sample of
      50 healthy children (mean +/- SD age, 6.3 +/- 1.3 years) and 20 adults. MAIN
      OUTCOME MEASURES: After each antibiotic test dose, subjects rated its taste on a
      10-cm visual analog scale incorporating a facial hedonic scale. RESULTS: The mean
      +/- SD taste scores of the antibiotics as rated by the children were as follows:
      amoxicillin-clavulanic acid, 5.7 +/- 3.6 cm; azithromycin, 6.8 +/- 3.2 cm;
      clarithromycin, 3.7 +/- 3.6 cm; and erythromycin-sulfisoxazole, 4.9 +/- 3.5 cm.
      The mean +/- SD taste score for erythromycin-sulfisoxazole (ie, 2.7 +/- 2.3)
      assigned by the adults was significantly different than that given by the
      children (P = .01) with no difference noted for the other 3 drugs. Children and
      adults both selected azithromycin most often as best tasting. There was a
      significant difference in the proportions selecting each antibiotic as worst
      tasting, with the children tending to dislike clarithromycin and the adults
      tending to dislike erythromycin-sulfisoxazole (P = .03). CONCLUSIONS: The taste
      of azithromycin was rated most highly by both children and adults, who also
      selected this antibiotic most often as best tasting. Differences in taste-testing
      results between children and adults suggest that evaluation of the palatability
      of medications intended for use in pediatrics should be conducted in children.

PMID- 9193247
TI  - Parent and adolescent perceived need for parental consent involving research with
      minors.
AB  - OBJECTIVE: To assess parents' and adolescents' perceived need for parental
      consent for minor adolescents to participate in minimal risk research studies
      based on procedural invasiveness (anonymous surveys, interviews, and blood or
      urine testing) and sensitivity of the topics (sexuality, drug and alcohol use,
      and sexually transmitted diseases and human immunodeficiency virus [HIV]).
      METHODS: An anonymous self-report questionnaire was administered to 100
      adolescent-parent pairs at 2 clinical sites (urban and suburban) of Children's
      Hospital of Michigan in Detroit. RESULTS: By invasiveness of the research
      procedure, the proportions of parents and adolescents who perceived a need for
      parental consent were as follows: face-to-face interviews, 62% vs 48%; telephone
      interviews, 72% vs 46%; blood or urine testing, 77% vs 62%; and blood testing for
      HIV status, 78% vs 59%. These differences were only significant for telephone
      interviews and HIV blood testing. For anonymous surveys, a minority of parents
      (33%) and adolescents (26%) reported that parental consent was needed. Based on
      sensitivity of the research topics, the proportions of parents and adolescents
      who perceived a need for parental consent were as follows: sexuality, 60% vs 34%;
      drug and alcohol use, 56% vs 44%; contraception, 62% vs 46%; and sexually
      transmitted diseases and HIV testing, 56% vs 52%. These differences were only
      significant for sexuality. Parents with higher education believed that teens
      could give their own consent (P < .05). Fifty-seven percent of parents and their
      teens agreed that parental consent for anonymous surveys was not necessary. For
      more invasive procedures and more sensitive topics, the percentage of
      disagreement ranged from 28% to 55.5%. CONCLUSIONS: There is a greater perceived
      need for parental consent to adolescent participation in research studies among
      parents than among teens for more invasive procedures and more sensitive topics.
      These results suggest the need for sensitivity to differing adolescent and
      parental perceived need for parental consent for a minor adolescent to
      participate in such studies. Further studies with larger samples are needed to
      determine what factors influence diverse parent and adolescent opinions.

PMID- 9193248
TI  - An ethics curriculum for the pediatric residency program. Confronting barriers to
      implementation.
AB  - BACKGROUND: The 1997 Residency Review Committee requirements in pediatrics
      mandate a structured curriculum in medical ethics for all accredited pediatric
      residency programs. To our knowledge, there are no published models for the
      development of an ethics curriculum for pediatric residents. Several obstacles
      may confront those attempting to begin an ethics teaching program. OBJECTIVE: To
      describe the successful implementation of a structured ethics curriculum for
      pediatric residents. METHODS: Our program was designed to overcome the following
      obstacles: (1) time constraints of faculty and residents, (2) scheduling
      difficulties and lack of continuity, (3) attitudes of residents toward the
      material, and (4) inadequate ethics training among faculty. In addition to
      traditional topics in medical ethics, the curriculum focuses on issues that
      confront residents primarily during their training, issues that may shape their
      professional values in important ways. RESULTS: This ethics curriculum has been
      successfully implemented in our own program and offers solutions to common
      barriers faced by those seeking to implement an ethics curriculum for pediatric
      residents. CONCLUSION: We present the ethics curriculum currently in use at our
      institution as a tool that may be adopted as it stands or as altered by others as
      they develop their own program's ethics curriculum. We believe the proposed
      curriculum directly confronts many of the barriers to successful ethics education
      of pediatric residents.

PMID- 9193249
TI  - The purpose and functions of immunization information systems within health care
      organizations.
AB  - Abroad coalition of public and private health care organizations advocate the
      development of computerized immunization information systems as a key national
      strategy for achieving and sustaining high immunization coverage levels. However,
      widespread adoption requires greater awareness of the purpose, functions, and
      value of an immunization information system within health care organizations. We
      propose that the purpose of an immunization information system is to increase the
      efficiency and effectiveness of immunization-related practices and identify 9
      potential functions that accomplish this purpose through improving patient care
      and practice management. When implementing an immunization information system
      within a practice setting, health care providers must consider technological and
      organizational issues. Health care providers should also look beyond their
      particular practice setting and establish public-private partnerships to create a
      system that links immunization data from all health care providers.

PMID- 9193250
TI  - Radiological case of the month. Battered child syndrome.

PMID- 9193251
TI  - Radiological case of the month. Homozygous familial hypercholesterolemia.

PMID- 9193252
TI  - Picture of the month. Folliculitis, furunculosis, and carbuncles.

PMID- 9193253
TI  - Pathological case of the month. Pemphigus vulgaris.

PMID- 9193254
TI  - Pathological case of the month. Rhabdoid tumor of the kidney.

PMID- 9193255
TI  - A snake with 2 heads? Pitfalls in diagnosis and management of uterus didelphys
      with obstructed hemivaginae.

PMID- 9193256
TI  - Single ring- or disk-enhancing computed tomographic lesion in Indian children and
      adolescents after first seizure.

PMID- 9193257
TI  - Resumption of menses in anorexia nervosa.

PMID- 9193258
TI  - Quality medical care, physicians, and risk managers.

PMID- 9193259
TI  - Screening strategies for elevated blood lead levels.

PMID- 9193260
TI  - Preoperative anxiety in children. Predictors and outcome.

PMID- 9193261
TI  - Worth a careful look.

PMID- 9193262
TI  - Breast conservation: long-term results from Westmead Hospital.
AB  - BACKGROUND: Breast conservation has been shown to be a safe and effective
      alternative to mastectomy in early-stage breast cancer. The present study reviews
      the long-term outcome and toxicity after treatment of early breast cancer by
      conservative surgery and radiation. METHODS: Between November 1979 and December
      1989, 438 patients with Union Internationale Contre le Cancer (UICC) stage I or
      II breast cancer were treated with conservative surgery and radiation therapy
      (CS+RT) at Westmead Hospital. Surgery to the breast varied from a local excision
      to a quadrantectomy, depending on the preference of the referring surgeon. The
      axilla was surgically dissected in 299 patients (68%). All patients received
      postoperative breast irradiation. The whole breast was irradiated to 46-54 Gy
      (median dose, 50 Gy) using 6 Mev photons for 5-6.5 weeks. Boosts were given at
      the primary tumour site in 336 patients (78%), by electron therapy (88 patients),
      iridium-192 (247 patients) or photons (one patient). A total of 44 patients (10%)
      received adjuvant chemotherapy. RESULTS: The median follow-up period for
      surviving patients was 84 months (range: 56-172 months). The 5-year actuarial
      rate of local recurrence was 6% (312 patients at risk), and the 10-year rate was
      10% (52 patients at risk). Very young patients (aged 34 years at diagnosis) had a
      5-year actuarial rate of local recurrence of 13% compared to 5% for older
      patients (P = 0.04). Neither the total dose to the primary site nor the boost
      technique influenced local recurrence. The 5-year freedom from distant relapse
      was 83%. The side effects included rib fractures (2%), symptomatic pneumonitis
      (3%), fatty necrosis or fibrosis requiring surgery (4%), and moderate-severe
      oedema of the arm (7%). CONCLUSIONS: The long-term data show that CS+RT for UICC
      stage I or II breast cancer results in low rates of local recurrence which are
      influenced by age at diagnosis, but not by radiation dose or boost technique.
      These results confirm those of other international series that CS+RT is a safe
      alternative to mastectomy for most women with operable breast cancer.

PMID- 9193263
TI  - Core biopsy for microcalcifications in the breast.
AB  - BACKGROUND: The conventional method of dealing with clustered mammographic
      microcalcification in the breast when it is of uncertain aetiology is to
      undertake either a short-term mammographic review or to surgically excise the
      abnormal area and submit it for histological examination. Stereotactic wide-bore
      needle biopsy (core biopsy) of microcalcifications is a suitable alternative to
      surgical biopsy and experience with this technique forms the basis of the present
      study. METHODS: Percutaneous core biopsy has been used at the Wesley Breast
      Clinic as a means of assessing clustered calcification in 297 cases from November
      1992 to October 1995. The procedure is done under local anaesthesia as an
      outpatient procedure using a stereotactic attachment to a standard mammography
      unit. RESULTS: A diagnosis of frank malignancy was made on core samples in 22
      cases (7.4%), and in all of these malignancy was confirmed at open surgical
      biopsy. In a further six women in whom the core biopsy was reported as
      'suspicious of malignancy', open surgical biopsy confirmed malignancy in three
      women, lobular in situ carcinoma was found in two women, and atypical ductal
      hyperplasia in one woman. In two instances the core sample was reported as
      showing atypical ductal hyperplasia and in those cases, this was confirmed at
      open surgical biopsy. In 265 cases (89%) the histology of the core revealed
      appearances of benign breast tissue. Open surgical biopsy has been undertaken in
      only six of these cases, but in all instances the histology has confirmed a
      benign process. In the two remaining cases, the procedure was considered to be
      technically unsatisfactory, and open surgical biopsy was recommended because of
      doubt about the appearance of the microcalcification. In both instances,
      malignancy was demonstrated. CONCLUSIONS: Core biopsy of clustered mammographic
      microcalcification of uncertain aetiology is recommended as a satisfactory and
      reliable alternative to open surgical biopsy. It is less expensive, can be done
      quickly, produces few complications, and does not produce subsequent mammographic
      distortion.

PMID- 9193264
TI  - Pre-operative histological diagnosis of breast cancer.
AB  - BACKGROUND: A concordant triple assessment (clinical, mammographic and
      cytological) diagnosis of breast malignancy allows for pre-operative planning of
      surgery and may also allow for one-stage surgery. However, while the accuracy of
      cytology is high, it is unable to distinguish invasive cancer from ductal
      carcinoma in situ (DCIS). A malignant mass may be due to pure in situ cancer and
      hence axillary dissection may be avoided if pre-operative histology is available.
      METHODS: A consecutive series of 300 cases of breast cancer treated over the last
      5 years by the two authors was analysed to determine: the method of achieving pre
      definitive operation histology; the number of stages of surgery required; and the
      number of cases of mass-forming DCIS which could be susceptible to over
      treatment. RESULTS: Of 289 patients undergoing local definitive surgery for
      breast cancer, 12 (42%) had clinical masses predominantly due to DCIS and in most
      of these patients axillary dissection was avoided. Histology was obtained prior
      to definitive surgery in 272 (94.1%) patients, by intra-operative frozen section
      in 159 (55.0%), incisional biopsy in 37 (12.8%), needle localization biopsy in 62
      (21.5%) and core biopsy in 14 (4.8%). A total of 189 patients (65.4%) underwent
      one-stage surgery only. Breast conservation was achieved in 210 (72.7%) patients.
      Those requiring mastectomy were significantly more likely to have required two
      stages of surgery as were those with lesions detected by screening. CONCLUSIONS:
      Mass-forming DCIS cannot be predicted pre-operatively by triple assessment alone;
      and therefore pre-operative histology is required to avoid axillary dissection.
      Pre-operative histology may be obtained by core biopsy or intra-operative frozen
      section to identify DCIS and distinguish it from invasive disease, but both allow
      a one-stage surgical procedure in the majority of cases.

PMID- 9193265
TI  - The cost benefit of changing protocols in the management of intussusception.
AB  - BACKGROUND: At a time when pressure is being applied to healthcare systems to
      reduce costs and improve efficiency, both the medical and financial implications
      of changing practices need to be documented. METHODS: A review was undertaken of
      703 patients with intussusception, treated during a 10-year period from 1983.
      RESULTS: This review showed that changes to the protocol for the management of
      intussusception have not only benefited the patient by reducing the morbidity and
      the operative rate, but also have led to a reduction in the length of hospital
      stay, providing significant cost savings to the health system. The reduction in
      the operative rate accounts for an estimated annual saving at the Royal
      Children's Hospital of $139,000. CONCLUSIONS: Improvements in the management of
      intussusception have resulted in significant reductions in the costs of
      treatments. The recent diagnosis-related group casemix funding arrangements mean,
      however, that the Royal Children's Hospital benefits more financially from
      inappropriate operative management of intussusception, than from non-operative
      management. Funding arrangements should not discourage optimal treatment.

PMID- 9193266
TI  - The role of laparoscopy in evaluation of the impalpable undescended testis.
AB  - BACKGROUND: The evaluation and management of the impalpable testis remains
      controversial. The authors' experience with laparoscopy for the treatment of this
      condition is reported here. METHODS: All children with impalpable testes
      underwent an examination under anaesthetic and if negative, a laparoscopy was
      performed to locate the testis. A prospective evaluation was undertaken to
      determine the success and morbidity of this approach. RESULTS: Thirty-six
      children (median age 2.5 years) underwent laparoscopy to localize 40 impalpable
      testes. In 32 patients with unilateral impalpable testis, 10 were intra
      abdominal, nine were absent. In 13 patients, the vas and vessels entered the
      groin, and in 12 of these a small testis remnant was excised and in the other a
      normal-looking testis was brought down. In four patients with bilateral
      impalpable testes, one testis was absent, three testes were intra-abdominal and
      four were small testis remnants in the groin. The average laparoscopy time was 15
      min, and 34 of 36 children were operated on as day-stay cases. One child had an
      omental hernia via a port site. CONCLUSION: Laparoscopy is safe and effective at
      localizing impalpable testes in children and can be performed as day-stay
      procedures in the majority of cases.

PMID- 9193267
TI  - Anatomical landmarks of the inguinal canal in prepubescent children.
AB  - BACKGROUND: Most adult anatomical texts state that the deep inguinal ring is
      situated midway between the anterior superior iliac spine and the pubic tubercle.
      The aim of this study was to determine if this was true in prepubescent children.
      METHODS: A total of 107 inguinal ligaments and canals were measured during
      inguinal operations in 80 children (68 boys, age range 1-118 months). RESULTS:
      The length of the inguinal ligament increased from a median of 4.3 cm (range 3.6
      6.8) at less than 1 year of age to 7.5 cm (range 6.7-10.1) at over 4 years of
      age. The internal ring was situated medial to the midpoint of the inguinal
      ligament throughout childhood. The ratio of internal ring to public tubercle over
      inguinal ligament length was 42% (range 27-58) at less than 2 years; and 34%
      (range 25-46) at over 4 years. The inguinal canal remained short (median 1 cm
      (range 0.7-1.1) at less than 2 years, and median 1.1 cm (range 0.7-2.3) at over 4
      years) suggesting that growth of the inguinal region in this age group occurs
      outside the canal. CONCLUSIONS: These results have implications for the siting of
      incisions, and question the necessity of opening the inguinal canal in children.

PMID- 9193268
TI  - Handlebar injuries in children: patterns and prevention.
AB  - BACKGROUND: Bicycle handlebar injuries in children are a significant cause of
      abdominal trauma. The present study documents 32 children with handlebar injuries
      who were managed at the Royal Children's Hospital over a 5-year period, and
      suggests a design change to bicycle handlebars which may reduce the severity of
      injury. METHODS: A retrospective review of all the children admitted to the Royal
      Children's Hospital with handlebar injuries between January 1990 and January 1995
      was undertaken. The age, sex, nature of injury, length of hospital stay and
      management were recorded. RESULTS: Thirty-two children with blunt abdominal
      trauma or lacerations resulting from handlebar injuries were identified. Injuries
      included: splenic trauma (9); liver trauma (4); traumatic pancreatitis (3);
      transection of the pancreas (2); renal contusions (2); duodenal haematoma (1);
      and bowel perforation (3). In addition, there were three urethral injuries and
      five lacerations involving the abdominal wall and inguino-scrotal region. The
      presence of external bruising was a poor indicator of underlying brgan damage.
      Thirteen operations were performed and the mean hospital stay for the series was
      9 days. CONCLUSIONS: Handlebar injuries are a significant cause of both blunt
      abdominal trauma and lacerations to the contact area. The infrequent finding of
      external bruising in the presence of major organ damage suggests that, although
      the velocity at impact may be relatively low, the small cross-sectional area of
      the end of the handlebar is a major factor contributing to organ damage.
      Moreover, we suspect that the high proportion of lacerations observed in this
      type of trauma result from the sharp metallic end of the handlebar cutting
      through the soft rubber handle. Manufacturers of bicycles should be made aware of
      these findings and should adjust the design of the handlebars accordingly.

PMID- 9193269
TI  - An audit of early hospital readmission after primary knee joint replacement.
AB  - BACKGROUND: Hospital readmissions following arthroplasty represent a considerable
      burden to the community. The present study investigates the magnitude of this
      problem and the reasons for early readmission. METHODS: The medical records of
      patients who underwent primary knee joint replacements between July 1989 and
      December 1994 were reviewed retrospectively. Readmission within 12 months of
      surgery was noted and the prognosis of these patients assessed. RESULTS: A total
      of 160 patients (180 arthroplasties) were appropriate for review. The readmission
      rate for knee-related morbidity was 18%. The main reasons for this included pain,
      stiffness, and the investigation/management of an inflamed joint. Notably,
      patellofemoral disease was common, particularly in the group without resurfaced
      patellae, manipulation of a stiff joint was rarely effective unless instituted
      early and aetiologies aside from sepsis often resulted in the patient returning
      with an inflamed joint. CONCLUSIONS: Readmission is a significant problem which
      heralds a poor 12-month prognosis.

PMID- 9193270
TI  - The results of coraco-clavicular slings for acromio-clavicular dislocation.
AB  - BACKGROUND: Treatment of type 3 acromio-clavicular (A-C) dislocations is
      controversial. There have been over 60 different surgical procedures as well as a
      variety of conservative measures used to treat this injury. METHODS: The outcome
      of a coraco-clavicular (C-C) sling for grade 3-4 A-C dislocation was studied. A
      dissolvable sling of braided 1 polydioxanone (PDS, Ethicon) was used with or
      without excision of the distal end of the clavicle in six patients. The clinical
      and radiological outcome of the braid and acromio-clavicular joint were studied
      by clinical examination, plain and stress radiographs and magnetic resonance
      imaging (MRI). RESULTS: All patients reported good-excellent results from 6
      months after surgery. Radiological examination demonstrated some superior
      clavicular migration in all patients within 1 month of the procedure, although
      never more than that seen with a grade 2 dislocation. This migration was
      clinically evident only in patients with a thin build. At 1 month, the MRI
      demonstrated partial replacement of the braid by granulation tissue. From 6
      months on, the braid was absent and fibrous tissue was noted between the coracoid
      and the clavicle and the acromion and clavicle. CONCLUSIONS: The coraco
      clavicular sling did not maintain operative reduction of the dislocated clavicle.
      This did not diminish the functional result but was a cosmetic complication in
      patients with a thin build.

PMID- 9193271
TI  - Safety of silicone liquid in the postoperative management of Dupuytren's
      contracture.
AB  - BACKGROUND: Recently the New Zealand Department of Health expressed concerns
      about the safety of applying silicones to open wounds and banned their use. For
      30 years silicone liquid has been used for the management and rehabilitation of
      the injured hand. It has been reported that the application of silicone fluids to
      the skin and ordinary handling over a period of years of various methyl and
      phenyl polymers by laboratory workers caused no skin disorders or sensitization,
      nor was absorption observed. There are no reports in the literature of the safety
      of the use of silicones applied to open wounds. METHODS: In the present study,
      116 hands that had been mobilized in silicone liquid following surgery for
      Dupuytren's contracture over the last 12 years were reviewed. In the cases of 64
      hands, the patients could be traced and contacted, and 47 patients (hands) agreed
      to attend for a clinical review. The hands were examined for areas of
      inflammation, granuloma formation and abnormal scar formation. RESULTS: No
      patient showed any evidence of adverse effects from the use of silicone liquid.
      CONCLUSIONS: There is no evidence that the use of silicone liquid, in contact
      with open wounds of the hands, for the mobilization of the hand following surgery
      for Dupuytren's contracture has any of the adverse effects reported as being
      associated with implanted silicone prostheses.

PMID- 9193273
TI  - Transurethral resection of the prostate: still the gold standard.
AB  - BACKGROUND: In recent times there has been a number of newer methods advocated as
      treatment for bladder outlet obstruction. Prior to embracing these newer
      technologies, the authors' experiences with conventional transurethral resection
      of the prostate should be evaluated and compared with those experienced in the
      newer modalities. The objective was to determine whether a standard transurethral
      resection of the prostate (TURP) still compared favourably with the newer
      modalities in terms of duration of stay, duration of catheterization, re
      admission rate, re-catheterization rate, cost and long-term results. The results
      are compared with those of workers whose level of expertise was the best that
      could be achieved with transurethral needle ablation (TUNA) and laser
      prostatectomy. METHODS: During the 3-year period from September 1992 to September
      1995, 575 TURP were carried out in a regional hospital. The total duration of
      stay, the postoperative duration of stay, the re-catheterization and re-admission
      rates were assessed and the costs estimated. RESULTS: Transurethral resection of
      the prostate was shown to compare favourably in terms of the duration of hospital
      admission and the duration of catheterization, and to have a significantly lower
      re-catheterization rate and a significantly lower re-admission rate than the
      newer modalities. CONCLUSION: Transurethral resection of the prostate is still
      the method of choice for surgical management of bladder outlet obstruction, and
      it remains as the gold standard. Having reviewed the results of the newer
      modalities as carried out by the experts in those fields, it was found that TURP
      compares favourably with those procedures. From the point of view of duration of
      stay, duration of catheterization, re-admission rate and re-catheterization rate,
      as well as cost and long-term results, TURP remains as the gold standard and the
      newer modalities are not believed to be advantageous at this stage.

PMID- 9193272
TI  - Typhoid enteric perforation.
AB  - BACKGROUND: Perforation of the bowel is the most serious complication of typhoid
      fever. The role of early limited surgery in managing these patients needs to be
      assessed. METHODS: The records of 110 cases of typhoid enteric perforation
      treated at JLN Hospital, Ajmer between 1990 and 1995 were reviewed. RESULTS: A
      total of 42.7% of the patients were in the 21-30-year age group, and 83.6% were
      male. All patients presented with the classic features of typhoid enteric
      perforation. A total of 83.6% were operated on within 36 h of perforation.
      Surgical management consisted of primary closure of the perforation (74.5%),
      closure with omental graft (14.5%), resection and anastomosis (3.6%), and only
      drainage (7.3%). A total of 79.1% of patients developed wound infection and 10%
      of patients developed faecal fistula. The overall mortality rate was 16.4%.
      Increasing the time interval between perforation and operation significantly
      increased the mortality (P < 0.05). The mortality was least with early primary
      closure of the perforation. Patients with postoperative faecal fistula had higher
      mortality rates (P < 0.001). CONCLUSIONS: Early limited surgery with thorough
      peritoneal lavage provides optimal results, faecal fistula is a grave
      complication, and the use of the McBurney incision may provide better results in
      terms of subsequent wound healing.

PMID- 9193274
TI  - Cochlear implants in adults and children: summary of the NIH consensus. Office of
      Medical Applications of Research, National Institutes of Health.

PMID- 9193275
TI  - Nasal amputation due to human bite: microsurgical replantation.

PMID- 9193276
TI  - A case of local tissue necrosis following a bite by the Australian tiger snake
      Notechis scutatus.

PMID- 9193277
TI  - Survival after traumatic complete transection of the trachea.

PMID- 9193278
TI  - Intractable anal pain due to ischaemic proctitis caused by venous obstruction.

PMID- 9193279
TI  - Cardiopulmonary bypass using lomoparan: monitoring of anticoagulation using anti
      Xa levels and thromboelastography.

PMID- 9193280
TI  - Managing chronic fatigue syndrome in children.

PMID- 9193281
TI  - Why healthcare systems need medical managers.

PMID- 9193282
TI  - Health priorities for the European intergovernmental conference.

PMID- 9193283
TI  - Treating anal fissure.

PMID- 9193284
TI  - Why does acute back pain become chronic?

PMID- 9193285
TI  - Drugs for obesity are last resort treatment.

PMID- 9193286
TI  - Jewish paper forgoes tobacco advertising.

PMID- 9193288
TI  - Canada plans new regulations on hepatitis B.

PMID- 9193287
TI  - Philippines considers euthanasia bill.

PMID- 9193289
TI  - Tilting at the immunisation windmill.

PMID- 9193290
TI  - Simultaneous immunisation with influenza vaccine and pneumococcal polysaccharide
      vaccine in patients with chronic respiratory disease.

PMID- 9193291
TI  - Acute dissection of the aorta with amphetamine misuse.

PMID- 9193292
TI  - Systematic review of randomised controlled trials of multiple risk factor
      interventions for preventing coronary heart disease.
AB  - OBJECTIVE: To assess the effectiveness of multiple risk factor intervention in
      reducing cardiovascular risk factors, total mortality, and mortality from
      coronary heart disease among adults. DESIGN: Systematic review and meta-analysis
      of randomised controlled trials in workforces and in primary care in which
      subjects were randomly allocated to more than one of six interventions (stopping
      smoking, exercise, dietary advice, weight control, antihypertensive drugs, and
      cholesterol lowering drugs) and followed up for at least six months. SUBJECTS:
      Adults aged 17-73 years, 903000 person years of observation were included in nine
      trials with clinical event outcomes and 303000 person years in five trials with
      risk factor outcomes alone. MAIN OUTCOME MEASURES: Changes in systolic and
      diastolic blood pressure, smoking rates, blood cholesterol concentrations, total
      mortality, and mortality from coronary heart disease. RESULTS: Net decreases in
      systolic and diastolic blood pressure, smoking prevalence, and blood cholesterol
      were 4.2 mm Hg (SE 0.19 mm Hg), 2.7 mm Hg (0.09 mm Hg), 4.2% (0.3%), and 0.14
      mmol/l (0.01 mmol/l) respectively. In the nine trials with clinical event end
      points the pooled odds ratios for total and coronary heart disease mortality were
      0.97 (95% confidence interval 0.92 to 1.02) and 0.96 (0.88 to 1.04) respectively.
      Statistical heterogeneity between the studies with respect to changes in
      mortality and risk factors was due to trials focusing on hypertensive
      participants and those using considerable amounts of drug treatment, with only
      these trials showing significant reductions in mortality. CONCLUSIONS: The pooled
      effects of multiple risk factor intervention on mortality were insignificant and
      a small, but potentially important, benefit of treatment (about a 10% reduction
      in mortality) may have been missed. Changes in risk factors were modest, were
      related to the amount of pharmacological treatment used, and in some cases may
      have been overestimated because of regression to the mean, lack of intention to
      treat analyses, habituation to blood pressure measurement, and use of self
      reports of smoking. Interventions using personal or family counselling and
      education with or without pharmacological treatments seem to be more effective at
      reducing risk factors and therefore mortality in high risk hypertensive
      populations. The evidence suggests that such interventions implemented through
      standard health education methods have limited use in the general population.
      Health protection through fiscal and legislative measure may be more effective.

PMID- 9193293
TI  - The thalassaemias.

PMID- 9193294
TI  - ABC of mental health. Common mental health problems in hospital.

PMID- 9193295
TI  - Fraction of normal remaining life span: a new method for expressing survival in
      cancer.

PMID- 9193296
TI  - The one child family policy: the good, the bad, and the ugly.
AB  - Rapid population growth in China during the 1950s and '60s led to the "late,
      long, few" policy of the 1970s and a dramatic reduction in the total fertility
      rate. However, population growth remained too high for the economic targets of
      Deng Xiao Ping's reforms, so the one child family policy was introduced in 1979
      and has remained in force ever since. The strategy is different in urban and
      rural areas, and implementation varies from place to place depending on local
      conditions. The policy has been beneficial in terms of curbing population growth,
      aiding economic growth, and improving the health and welfare of women and
      children. On the negative side there are concerns about demographic and sex
      imbalance and the psychological effects for a generation of only children in the
      cities. The atrocities often associated with the policy, such as female
      infanticide, occur rarely now. China may relax the policy in the near future,
      probably allowing two children for everyone.

PMID- 9193297
TI  - The WHO wants governments to encourage people to stop smoking.

PMID- 9193298
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Conflicting results from the Helisal test.

PMID- 9193299
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Assessment lacked certain considerations.

PMID- 9193300
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Test needs full evaluation in primary care.

PMID- 9193301
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Endoscopy of only those who are positive for H pylori could miss other
      diagnoses.

PMID- 9193302
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Likelihood ratios should be routinely reported.

PMID- 9193303
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. Likelihood ratios provide more information with little effort.

PMID- 9193304
TI  - Validation of a rapid whole blood test for diagnosing Helicobacter pylori
      infection. A crucial reference just missed being cited.

PMID- 9193305
TI  - Interruption of methadone treatment by imprisonment.

PMID- 9193306
TI  - Major journals should peer review trials at protocol stage.

PMID- 9193307
TI  - Managing measles. Size of infecting dose may be important.

PMID- 9193308
TI  - Managing measles. Crystal violet and eye pads should not be recommended.

PMID- 9193309
TI  - Managing measles. Giving paracetamol for fever is unnecessary.

PMID- 9193310
TI  - Elimination of firearms would do little to reduce premature deaths.

PMID- 9193311
TI  - Severe persistent visual field constriction associated with vigabatrin. Chronic
      refractory epilepsy may have role in causing these unusual lesions.

PMID- 9193312
TI  - Severe persistent visual field constriction associated with vigabatrin. Reaction
      might be dose dependent.

PMID- 9193313
TI  - Severe persistent visual field constriction associated with vigabatrin. Patients
      taking vigabatrin should have regular visual field testing.

PMID- 9193314
TI  - Severe persistent visual field constriction associated with vigabatrin. Four
      possible explanations exist.

PMID- 9193316
TI  - Swiss experience of managed care.

PMID- 9193315
TI  - Severe persistent visual field constriction associated with vigabatrin.
      Manufacturers have started several studies.

PMID- 9193317
TI  - WHO is producing a reproductive health library for developing countries.

PMID- 9193318
TI  - Looking through the retrospectoscope in the era of evidence-based medicine.

PMID- 9193319
TI  - Dose-intensity in ovarian carcinoma: hold, enough?

PMID- 9193320
TI  - Supratentorial low-grade glioma in adults: an analysis of prognostic factors and
      timing of radiation.
AB  - PURPOSE: To review the outcomes of patients with low-grade glioma diagnosed by
      modern imaging and treated at a center where postponing radiotherapy was common
      practice. METHODS: We reviewed the records of patients (age > or = 18 years) with
      pathologically confirmed supratentorial low-grade fibrillary astrocytoma,
      oligodendroglioma, and mixed glioma treated at a regional cancer center in Canada
      between 1979 and 1995. RESULTS: Median survival for the entire group (N = 167;
      mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and
      50%, respectively. Median progression-free survival was 4.9 years with 5- and 10
      year progression-free rates of 50% and 12%, respectively. Overall and progression
      free survivals were longer for patients with an oligodendroglioma or mixed glioma
      than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v
      4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation,
      minimal residual tumor after surgery, Karnofsky performance status > or = 70, and
      oligodendroglioma or mixed glioma pathology were associated with significantly
      longer median survival on univariate and multivariate analyses. Radiotherapy
      deferred until tumor progression (v immediate radiotherapy) was associated with
      longer survival on univariate analysis, but an imbalance in other variables
      accounted for this advantage such that timing of radiotherapy was not an
      independent (favorable or adverse) prognostic factor on multivariate analysis.
      CONCLUSION: Patients with low-grade glioma diagnosed by modern imaging can be
      expected to live a long time; timing of radiotherapy may be a less important
      determinant of survival than nontreatment variables and residual tumor bulk.

PMID- 9193321
TI  - High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV
      ovarian cancer: long-term results.
AB  - PURPOSE: A series of 53 patients with poor-prognosis epithelial ovarian cancer
      treated with high-dose chemotherapy (HDC) followed by hematopoietic rescue was
      retrospectively studied from the day of diagnosis for toxicity and long-term
      survival analysis. PATIENTS AND METHODS: Patients were treated with surgery
      followed by cisplatin combination chemotherapy. After second-look operation
      (SLO), HDC was administered: 23 patients received melphalan (140 mg/m2 on day 1)
      and 30 patients received a combination of carboplatin (400 mg/m2 on days 1 to 4)
      and cyclophosphamide (1.6 g/m2 on days 1 to 4). After HDC, autologous stem-cell
      transplantation was performed for hematologic support. RESULTS: One patient died
      of cardiac failure after HDC, but the acute toxicity was acceptable for the other
      patients. With a median follow-up of 81.5 months, the 5-year overall survival
      rate for the 53 patients was 59.9% and the disease-free survival (DFS) rate at 5
      years was 23.6%. Twenty-four patients (45.3%) were alive, 12 with no evidence of
      disease and 12 with recurrent disease. The best results were achieved in 19
      patients with pathologic complete response at SLO (74.2% 5-year overall survival;
      32.8% 5-year DFS). CONCLUSION: HDC followed by autologous stem-cell support is a
      well-tolerated therapeutic approach for patients with poor-prognosis ovarian
      carcinoma. In this report, the 59.9% survival of 53 patients at 5 years must be
      compared to the 20% to 30% 5-year survival observed after conventional therapy.
      These results should be confirmed by an ongoing prospective randomized trial.

PMID- 9193322
TI  - High-dose chemotherapy with autologous transplantation for persistent/relapsed
      ovarian cancer: a multivariate analysis of survival for 100 consecutively treated
      patients.
AB  - PURPOSE: To examine the prognostic factors associated with prolonged progression
      free survival (PFS) and overall survival (OS) in 100 consecutively treated women
      undergoing autologous stem-cell transplant for advanced ovarian cancer. PATIENTS
      AND METHODS: From October 1989 to February 1996, we transplanted 100 patients
      with ovarian cancer following chemotherapy with high-dose carboplatin,
      mitoxantrone, and cyclophosphamide with or without cyclosporine (n = 70);
      melphalan and mitoxantrone with or without paclitaxel (n = 25); or other regimens
      (n = 5). Their median age was 48 years (range, 23 to 65), 70% had papillary
      serous histology, 72% had grade III tumors, 66% were platinum-resistant, and 61%
      had > or = 1 cm bulk. The median number of prior regimens was two (range, one to
      six). Univariate and multivariate analyses were performed to examine age (< v >
      or = mean), stage, initial bulk, histology, grade, response to initial therapy,
      number of prior regimens, time from diagnosis to transplant, transplant regimen,
      platinum sensitivity, and bulk (< v > or = 1 cm) at transplant. RESULTS: The
      median PFS and OS times for the 100 patients were 7 and 13 months. A stepwise Cox
      proportional hazards model identified tumor bulk (P = .0001), and cisplatin
      sensitivity (P = .0249) as the best predictors of PFS. Age (P = .0017), bulk at
      transplant (P = .0175), and platinum sensitivity (P = .0330) provided the best
      prediction of OS. The median PFS and OS times for the 20 patients with platinum
      sensitive, < or = 1-cm disease were 19 and 30 months. No differences in OS were
      seen when chemotherapy or surgery was used to achieve a minimal disease state.
      CONCLUSION: Before consideration of high-dose therapy for recurrent/persistent
      advanced ovarian cancer, patients should undergo debulking surgery or
      chemotherapy to achieve a minimal disease state. Patients with platinum
      resistant, bulky disease should not be transplanted. The optimal patients for
      this therapy may be those with minimal disease responsive to initial
      chemotherapy.

PMID- 9193323
TI  - Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced
      breast cancer.
AB  - PURPOSE: To determine the cardioprotective effect of dexrazoxane (DZR) used in a
      doxorubicin-based combination therapy in advanced breast cancer. PATIENTS AND
      METHODS: Between November 1988 and January 1991, 534 patients with advanced
      breast cancer were randomized to two multicenter, double-blind studies (088001
      and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide
      (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3
      weeks and were monitored with serial multiplegated acquisition (MUGA) scans.
      RESULTS: The hazards ratio (HR) of PLA to DZR for a cardiac event, which was
      predefined ejection fraction changes or congestive heart failure (CHF), was 2.63
      (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95%
      CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001
      were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P
      = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4%
      (95% CI, -13% to 22%; P = .63). Time to progression and survival were not
      significantly different between treatment arms in either study. Toxicities on the
      DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P
      = .004, respectively) and more pain on injection (P = .001), with no difference
      in the rates of fever, infection, or hemorrhage. CONCLUSION: DZR had a
      significant cardioprotective effect as measured by noninvasive testing and
      clinical CHF. One of the two studies (088001) showed a lower response rate with
      DZR, but time to progression and survival were not significantly different. DZR
      is the first agent shown to reduce cardiotoxicity from doxorubicin.

PMID- 9193324
TI  - Delayed administration of dexrazoxane provides cardioprotection for patients with
      advanced breast cancer treated with doxorubicin-containing therapy.
AB  - PURPOSE: To assess whether dexrazoxane (DZR) given after a cumulative doxorubicin
      dose of 300 mg/m2 confers cardioprotection in patients with advanced breast
      cancer treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC).
      PATIENTS AND METHODS: In two multicenter studies (088001 and 088006), patients
      were randomized to receive FAC and placebo (PLA) versus FAC and DZR. After a
      protocol amendment, all patients received open-label DZR after they had reached a
      cumulative doxorubicin dose of 300 mg/m2. Two groups were compared: 99 patients
      randomized to the PLA arms before the amendment who received FAC and PLA for at
      least seven courses (PLA group), and 102 patients randomized to the PLA arms
      after the amendment who received FAC and PLA for six courses followed by open
      label DZR (PLA/DZR group). RESULTS: The hazards ratio of PLA to PLA/DZR was 3.5
      (95% confidence interval [CI], 2.2 to 5.7; P < .001, logrank and generalized
      Wilcoxon tests) for the doxorubicin dose at any cardiac event, ejection fraction
      changes, or congestive heart failure (CHF). The hazards ratio of PLA to PLA/DZR
      was 13.1 (95% CI, 3.7 to 46.0; P < .001, logrank and generalized Wilcoxon tests)
      for the doxorubicin dose at the development of CHF. The overall incidence of CHF
      in the PLA/DZR group was 3%, compared with 22% in the PLA group (P < .001,
      Fisher's exact test). Twenty-six percent of PLA/DZR patients received at least 15
      courses of therapy, compared with 5% of patients in the PLA group. These results
      do not appear to be attributable to a time trend. CONCLUSION: DZR is a highly
      effective cardioprotective agent when used in patients with advanced breast
      cancer who continue to receive doxorubicin-based chemotherapy after a cumulative
      doxorubicin dose of 300 mg/m2 has been reached.

PMID- 9193325
TI  - Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and
      fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a
      randomized study in premenopausal breast cancer patients.
AB  - PURPOSE: In the majority of premenopausal breast cancer patients, an adjuvant
      chemotherapy-induced early menopause occurs, which is known to be a strong
      predictor of osteoporosis. We present data on the effect of adjuvant
      cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy on bone mineral
      density (BMD) and the efficacy of clodronate on the prevention of bone loss in
      148 premenopausal breast cancer patients without skeletal metastases. MATERIALS
      AND METHODS: Patients were randomized to receive oral clodronate 1,600 mg/d or to
      a control group. In addition, patients were treated with six cycles of CMF
      therapy. BMD of the lumbar spine and femoral neck was measured by dual-energy x
      ray absorptiometry (DEXA) before therapy and at 1 and 2 years. RESULTS: Changes
      in the BMD of lumbar spine and femoral neck were -5.9% and -2.0% without
      clodronate and -2.2% and +0.9% with clodronate at 2 years (P = .0005 and .017,
      respectively). Patients who developed amenorrhea after chemotherapy had a rapid
      bone loss, which was significantly reduced by clodronate. In controls, bone loss
      was 9.5% in the lumbar spine and 4.6% in the femoral neck, while in the
      clodronate group, bone loss was 5.9% and 0.4%, respectively, at 2 years. Patients
      with preserved menstruation had only marginal changes in BMD. CONCLUSION:
      Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal
      breast cancer patients. Women older than 40 years are at particularly high risk.
      Clodronate significantly reduces this bone loss.

PMID- 9193326
TI  - Evaluation of irradiated heart volumes in stage I breast cancer patients treated
      with postoperative adjuvant radiotherapy.
AB  - PURPOSE: To quantify the proportion of heart volumes that received at least 25 Gy
      with tangential photon fields in patients with left-sided stage I (T1 NOMO)
      breast cancer treated with breast-conserving surgery. METHODS AND MATERIALS: The
      dose planning of 100 consecutive patients was reviewed. All were irradiated with
      tangential photon fields that covered the left breast only. A three-dimensional
      computed tomographic (CT)-based dose planning was made for each patient. The
      prescribed dose to the tumor was 50 Gy. For each patient, the proportion of the
      heart included in the 50% isodose was determined from the cumulative dose-volume
      histogram (DVH). The same volume determination was made for the left-sided breast
      cancer patients treated with tangential fields during the first Stockholm Breast
      Cancer Trial. RESULTS: The mean irradiated heart volume that received at least 25
      Gy was 5.7% (SD = 4.5%) for the whole group and 11.9% (SD = 3.7%) in those with
      the highest volumes. The mean irradiated heart volume included in the 50% isodose
      for patients in the Stockholm Trial was 25% (SD = 11.9%). CONCLUSION: In this
      study, the majority of patients with left-sided T1NOMO breast cancer did not
      receive irradiation to substantial heart volumes. However, in 6% of all studied
      patients, the proportion of irradiated heart volume was close to the irradiated
      heart volumes with one of the treatment techniques used in the Stockholm Trial
      for patients with left-sided tumors. That technique has been associated with
      significantly increased cardiac mortality during long-term follow-up evaluation
      in a previous study. The CT-based three-dimensional treatment-planning system
      (TMS) represents a valuable tool in identifying such patients; thus, treatment
      may be conformed to reduce the irradiated heart volume.

PMID- 9193327
TI  - Tumor-cell number and viability as quality and efficacy parameters of autologous
      virus-modified cancer vaccines in patients with breast or ovarian cancer.
AB  - PURPOSE: We investigated quality and efficacy criteria of an autologous,
      physically and immunologically purified, Newcastle disease virus (NDV)-modified,
      irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a
      through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS:
      Included were 63 patients with primary breast cancer (a), 27 with metastatic
      pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer
      (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy
      as supportive treatment. After cryoconservation and purification, the vaccines
      varied in applied numbers of viable cells and dead cell contaminations. We
      retrospectively hypothesized that an immunogenic vaccine should contain at least
      1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort
      was thus divided into two groups; one that received vaccine type A (A),
      fulfilling both criteria; and the other type B (B), missing one or both criteria.
      RESULTS: Conventional prognostic factors were wall balanced between A and B in
      cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and
      disease-free survival (P = .089) for A. In addition, in cohort a, the relative
      risk of dying in the group that received A as compared with B was 0.2 (univariate
      Cox model). There were also survival trends in favor of A versus B (P = .18 and P
      = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42,
      respectively. In cohort b, the survival benefit could not be ascribed to vaccine
      quality alone, because of prognostic imbalance in favor of A. CONCLUSION: In
      cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV
      NDV vaccine quality, since prognostic factors were not biased. This could imply
      clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality
      vaccine. Furthermore, the data provide clinically relevant information for
      standardization and quality control of autologous tumor-cell vaccines. A
      randomized study is urgently needed.

PMID- 9193328
TI  - Comparative study of dose escalation versus interval reduction to obtain dose
      intensification of epirubicin and cyclophosphamide with granulocyte colony
      stimulating factor in advanced breast cancer.
AB  - PURPOSE: A potential application of hematopoietic growth factors is to obtain an
      increased dose-intensity. This can be achieved by either higher doses of
      chemotherapy with standard intervals, or by standard doses with shorter
      intervals. The potential of these approaches has not been investigated
      systematically. PATIENTS AND METHODS: In a randomized, multicenter study, 49
      advanced breast cancer patients were treated with granulocyte colony-stimulating
      factor (G-CSF) and either increasing doses of epirubicin and cyclophosphamide
      with fixed intervals (arm one) or progressively shorter intervals with fixed
      doses of epirubicin and cyclophosphamide (arm two). A cohort of at least six
      patients was studied at each interval/dose. A more intensified interval/dose was
      given if less than 50% of patients encountered a dose-intensity limiting
      criterium (DILC) in the first three courses. RESULTS: In arm one, epirubicin 140
      mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic. Subsequently,
      epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10
      patients encountering a DILC. All initial DILCs consisted of febrile neutropenia.
      In arm two, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be
      administered safely with 14- and 12-day intervals. In the 10-day interval, eight
      of 12 patients completed the first three cycles without a DILC. In the 8-day
      interval, seven of eight patients encountered a DILC. Incomplete neutrophil
      recovery, and to a lesser extent stomatitis, were dose-limiting. CONCLUSION: In
      combination with G-CSF, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every
      21 days was feasible (projected dose-intensity, 40 mg/m2/wk and 233 mg/m2/wk,
      respectively). Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be
      administered safely every 10 days, allowing a projected dose-intensity of 52.5
      mg/m2/wk and 350 mg/m2/wk, respectively.

PMID- 9193329
TI  - Fatty acid composition of adipose tissue, an indication of dietary fatty acids,
      and breast cancer prognosis.
AB  - PURPOSE: Fatty acid composition of adipose tissue is an indicator of the long
      term ingestion pattern of several specific fatty acids. There is good correlation
      of antecedent diet with the essential fatty acids, and there is reflection of the
      diet with the fatty acids that can be synthesized. The relationship between the
      fatty acid levels and lymph node status and clinical outcome was examined.
      METHODS: At the time of diagnostic surgery, 161 women with clinical stage T1NO
      breast cancer had subcutaneous adipose tissue (breast and abdominal) aspirated.
      The concentrations of 35 fatty acids, seven summed classes, and six fatty acid
      groups were measured by capillary gas chromatography. Lymph node status was
      determined with axillary dissection, and patients were followed-up (mean, 7.3
      years) for clinical outcome. RESULTS: There was no significant association of any
      adipose tissue fatty acids with overall survival, although few (16 of 161 women)
      died of breast cancer. However, the odds of having positive lymph nodes (57 of
      161 women) were significantly higher for women with a greater adipose tissue
      proportion of oleic acid (odds ratio [OR], 7.56; 95% confidence interval [CI],
      1.78 to 32.1) or total saturated acids (OR, 8.43; 95% CI, 1.48 to 40.0) and
      significantly lower with a higher proportion of trans fatty acids (OR, 0.24; 95%
      CI, 0.07 to 0.77), as assessed by multivariate logistic regression. CONCLUSION:
      These data support previous research with dietary questionnaire methodology,
      suggesting that specific dietary fatty acids may be associated with breast cancer
      promotion. Further research with long-term clinical follow-up is necessary to
      investigate these observations in large, diverse populations before dietary
      recommendations can be envisioned.

PMID- 9193330
TI  - Effectiveness of adjuvant chemotherapy in combination with tamoxifen for node
      positive postmenopausal breast cancer patients.
AB  - PURPOSE: Adjuvant tamoxifen has been shown to reduce relapse and mortality among
      node-positive post-menopausal breast cancer patients. The value of adding
      chemotherapy to tamoxifen is controversial. PATIENTS AND METHODS: Between July
      1986 and April 1993, 1,266 postmenopausal breast cancer patients with node
      positive disease were randomly assigned to receive one of four adjuvant therapy
      regimens: (A) tamoxifen alone for 5 years; (B) tamoxifen plus three courses of
      early cyclophosphamide, methotrexate, and fluorouracil (CMF) on months 1, 2, and
      3; (C) tamoxifen plus delayed single courses of CMF on months 9, 12, and 15; (D)
      tamoxifen plus early and delayed CMF on months 1, 2, 3, 9, 12, and 15. The two-by
      two factorial design allowed two direct comparisons: early CMF (B and D) versus
      no early CMF (A and C), and delayed CMF (C and D) versus no delayed CMF (A and
      B). Estrogen receptor (ER) status was known for all patients and was used to
      stratify the randomization. A total of 1, 212 patients (96%) were eligible and
      assessable. The median follow-up duration was 60 months. RESULTS: The results of
      the two-by-two factorial comparisons were as follows: (1) early CMF added to
      tamoxifen significantly improved 5-year disease-free survival (DFS; 64% v 57%;
      hazards ratio [HR], 0.79; 95% confidence interval [CI], 0.66 to 0.95; P = .01);
      and (2) delayed CMF added to tamoxifen did not improve DFS (5-year DFS, 61% v
      60%; HR, 0.97; 95% CI, 0.81 to 1.17; P = .77). For patients with ER-positive
      tumors, the addition of CMF, either early or delayed or both, reduced the
      relative risk of relapse by 22% to 36%. In contrast, for patients with ER
      negative tumors, tamoxifen with delayed CMF was associated with a nonsignificant
      increased risk of relapse (HR, 1.27; 95% CI, 0.92 to 1.76; P = .15). CONCLUSION:
      Postmenopausal patients with node-positive breast cancer should be offered
      combination chemotherapy in addition to tamoxifen. Tamoxifen should not be
      initiated before CMF, as this might be detrimental, especially for patients with
      ER-negative tumors.

PMID- 9193331
TI  - Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor
      support in paclitaxel-refractory metastatic breast cancer.
AB  - PURPOSE: We evaluated weekly single-agent intravenous (IV) vinorelbine as salvage
      therapy for metastatic breast cancer. After the first five patients, all received
      elective growth factor support with granulocyte colony-stimulating factor (G-CSF;
      filgrastim) in an attempt to maximize delivered dose-intensity (DDI). Objective
      tumor response, DDI, and toxicity were assessed, as well as time to progression
      (TTP) and survival. PATIENTS AND METHODS: This single-center nonrandomized trial
      enrolled 40 patients. Anthracycline exposure and subsequent progression were
      common to all patients, and 38 of 40 were paclitaxel-refractory. Vinorelbine was
      given initially at 30 mg/m2/wk, then at 35 mg/m2/wk in a phase I/II design, which
      involved first intermittent (6 days of 7) and then continuous (daily)
      administration of G-CSF at 5 micrograms/kg. RESULTS: The maximum-tolerated
      starting dose was 35 mg/m2/wk with continuous G-CSF support. The mean DDI was
      27.7 mg/m2/wk for all patients. There were two complete responses (CRs) and eight
      partial responses (PRs) in 40 assessable patients for an overall response rate of
      25% (95% confidence interval [CI], 13% to 41%). The median TTP was 13 weeks and
      median survival time 33 weeks. The dose-limiting toxicity was neutropenia, with
      dose delay or reduction required in 14 of 27 patients entered at 35 mg/m2.
      Febrile neutropenia that required hospitalization was unusual (three of 40
      patients, 8%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia
      occurred in nine patients (23%) and 26 patients (65%) required RBC transfusions
      for anemia. Seven patients (18%) had reversible grade 3/4 nonhematologic
      complications, primarily related to neurotoxicity. Grade > or = 3 mucositis was
      absent. CONCLUSION: Concurrent administration of weekly vinoralbine and daily G
      CSF is feasible and permits an increase in DDI for vinorelbine of 43% to 76% over
      that reported in series without growth factor support. The response rate, TTP,
      and survival data are encouraging for therapy given to heavily pretreated
      patients with metastatic breast cancer. Vinorelbine is not cross-resistant with
      paclitaxel and should be considered for further trials in the dose-intensified
      mode made possible by G-CSF, alone or combined with other agents.

PMID- 9193332
TI  - Measuring standards of care for early breast cancer in an insured population.
AB  - PURPOSE: To demonstrate the use of a combined data base to evaluate the care for
      local/regional invasive breast cancer in a large insured population of women aged
      less than 64 years. PATIENTS AND METHODS: We linked the procedural and hospital
      claims from Blue Cross Blue Shield (BCBS) of Virginia with clinical stage data
      from the Virginia Cancer Registry (VCR) from 1989 to 1991. A total of 918 women
      were assessed with a median age of 50 years; 68% had tumors less than 2 cm, 30%
      had positive axillary nodes, and 68% were assessed as having local summary stage.
      A quality-of-care "report card" was used based on standards of care from
      international Consensus Conferences. RESULTS: Eight percent had a mastectomy as
      the initial biopsy procedure. Sixty-nine percent of women ultimately underwent
      mastectomy. Of those women who underwent lumpectomy, 86% had subsequent
      radiation. Within 3 months of diagnosis, 43% had a bone scan and 20% a computed
      tomography (CT) scan. Of women with positive axillary lymph nodes, 83% aged less
      than 51 years and 52% aged 51 to 64 years received chemotherapy. Fifty-six
      percent of all women had claims from a medical oncologist. Of women having a
      total mastectomy, 27% had claims from a plastic surgeon. Sixty-six percent to 76%
      of women had a mammogram, 24% a bone scan, and 14% a CT scan in the 0-18 and 18
      36 month intervals following primary treatment. CONCLUSION: This study confirms
      the feasibility of linking sources of data that provide complementary information
      needed to develop measurements regarding standards of quality and efficiency of
      oncologic care. This report should serve as an initial benchmark while we await
      reports from other populations to define the best practice.

PMID- 9193333
TI  - Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced
      non-small-cell lung cancer: a phase I study.
AB  - PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity
      in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the
      antitumor effects of radiation therapy (RT). This study aimed to determine the
      maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately)
      when given concurrently with RT and to define the nature of the dose-limiting
      toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally
      advanced NSCLC received six weekly administrations of a CDDP-paclitaxel
      combination with concurrent local RT. The starting doses of CDDP and paclitaxel
      were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the
      dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy)
      and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last
      two cohorts of patients. The drug doses were escalated alternately until DLT
      occurred in more than one third of the patients in a given cohort. RESULTS:
      Overall, 25 patients were recruited through five different cohorts. All were
      assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of
      25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35
      mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue
      treatment because of severe esophagitis and one of these died of complications
      related to grade 4 esophagitis. However, keeping the same doses of chemotherapy
      and replacing hyperfractionation with a standard single-day fraction, weekly
      doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely
      administered. Neutropenia was by far the most relevant hematologic toxicity and
      occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only
      four courses. Substantial pulmonary or neurologic toxicity was not observed in
      this study. Two complete responses (CRs) and 13 partial responses (PRs) were
      observed, for a 60% overall response rate (95% confidence interval [CI], 39% to
      79%). The median survival time was 16 months, with a 66% 1-year survival
      probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be
      safely administered with concurrent standard RT. The use of hyperfractionation is
      associated with a more frequent occurrence of severe esophagitis and requires a
      reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will
      elucidate which of these two approaches (standard or hyperfractionated RT) is the
      better option to improve the outcome of patients with locally advanced NSCLC.

PMID- 9193334
TI  - Increasing 4'-epidoxorubicin and fixed ifosfamide doses plus granulocyte
      macrophage colony-stimulating factor in advanced soft tissue sarcomas: a pilot
      study.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of 4'-epidoxorubicin (EPI)
      in combination with full dose of ifosfamide (IFO) when granulocyte-macrophage
      colony-stimulating factor (GM-CSF) was used, to estimate its clinical efficacy,
      and to evaluate the mobilization of hematopoietic progenitors. PATIENTS AND
      METHODS: Previously untreated advanced patients were treated with fixed doses of
      IFO at 1.8 g/m2/d for 5 days and escalating doses of EPI. The starting dose level
      of EPI was 50 mg/m2 bolus on days 1 and 2; subsequent levels were 60 mg/m2 and 70
      mg/ m2 given on days 1 and 2. GM-CSF (5 micrograms/kg/d) was administered from
      days +6 to +19. Clinical evaluation of response was performed after three
      consecutive cycles. Mobilization of hematopoietic progenitors was evaluated as
      day 14 CFU-GM after the first cycle only. RESULTS: Overall, six, 18, and 13
      assessable patients were entered onto each EPI dose level, respectively. The
      first and the second EPI level were considered feasible. Conversely, at the third
      level, only six of 13 patients [46%] tolerated full EPI doses at the scheduled
      time. Therefore, the dose-intensity of the three levels was 100%, 99.7%, and
      86.1%, respectively. Overall, 20 of 37 patients (54%) obtained an objective
      response. The response rates for the three EPI dose levels were significantly
      different [17%, 33%, and 100%, respectively; test for trend, P < .001].
      Considering only lung metastases, the overall response rate was 72% (20%, 66%,
      and 100% for the three EPI levels, respectively). The most relevant mobilization
      effect was obtained at the third EPI level, when both GM-CSF and IL-3 were used
      as in vitro-stimulating factors. CONCLUSION: The third EPI level (70 mg/m2 on
      days 1 and 2) is the MTD of this program, since it was administered, without dose
      reduction or treatment delay, for three consecutive cycles in less than half of
      the patients. Nevertheless, this level proved to be interesting with regard to
      response rate (13 of 13 objective responses) and in mobilization of the
      hematopoietic progenitors.

PMID- 9193335
TI  - Salvage chemotherapy with vinblastine, ifosfamide, and cisplatin in recurrent
      seminoma.
AB  - PURPOSE: Salvage therapy for disseminated germ cell tumors of all histologic
      subtypes with vinblastine, ifosfamide, and cisplatin (VeIP) will cure
      approximately 25% of patients. The purpose of this study was to evaluate the
      activity of VeIP in patients with recurrent seminoma. PATIENTS AND METHODS: We
      conducted a retrospective review of 24 patients with recurrent seminoma who were
      treated at Indiana University with VeIP as second-line chemotherapy. All patients
      had received cisplatin-containing regimens as primary chemotherapy and seven had
      also received prior pelvic radiotherapy. All patients received four courses of
      VeIP. RESULTS: The minimum follow-up duration was 2 years (range, 2 to 9.1), with
      a median follow-up time of 7 years. Twenty of 24 patients (83%) achieved a
      complete remission (CR) following VeIP alone. One additional patient was rendered
      disease-free (NED) with the resection of residual carcinoma. Eight patients have
      relapsed. Four of six patients with extragonadal primary tumors and two of four
      who failed to achieve CR with initial chemotherapy are continuously NED with
      VeIP. Overall, 13 of 24 (54%) are long-term survivors with VeIP salvage
      chemotherapy. CONCLUSION: VeIP has significant curative potential in patients
      with recurrent seminoma and appears to produce a higher CR rate and more long
      term survivors than is achieved in patients with nonseminomatous disease.

PMID- 9193336
TI  - Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human
      interferon alfa-2b for liver metastases of colorectal cancer refractory to
      systemic fluorouracil and leucovorin.
AB  - PURPOSE: To determine the toxicity, response rate, and survival in patients
      treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus
      recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A; Schering-Plough,
      Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver metastases refractory
      to systemic 5-FU plus leucovorin (LCV). PATIENTS AND METHODS: Forty-eight
      patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m2 followed by an 18-hour
      HAI of 5-FU, 1,500 mg/m2 daily for 5 days. Twenty-nine patients were treated
      through percutaneously placed catheters and 19 through implantable infusion pumps
      (Shiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated every 28 to
      35 days. RESULTS: There were three (6.6%) complete remissions (CRs) and 12
      (26.6%) partial remissions (PRs), for a CR plus PR rate of 33.3% among 45
      assessable patients (95% confidence interval [CI], 20% to 49%). The median
      response duration was 7 months, while median survival duration was 15 months.
      Grade 3 to 4 treatment-related toxic effects included mucositis (40%),
      neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was
      encountered in any of the patients. Treatment was discontinued because of
      progressive liver disease in 23 patients and extrahepatic progression in 16,
      while six patients continue treatment through an infusaid pump. CONCLUSION: HAI
      of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity,
      and can produce a response rate of 33.3% among patients refractory to bolus
      intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicity may permit
      salvage HAI with floxuridine (FUDR) in patients whose liver tumors fail to
      respond to HAI of 5-FU plus rIFN-alpha 2b. Because diarrhea was not a common side
      effect of HAI of 5-FU plus rIFN-alpha 2b, it would be of interest to investigate
      whether alternating HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT
      11) will decrease the incidence of both hepatic and extrahepatic disease
      progression.

PMID- 9193337
TI  - Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the
      pancreas in cancer patients with pancreatic lesions.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is an important new tool in the staging
      of pancreatic malignancies. Using new curved linear-array instruments, real-time
      fine-needle aspiration biopsy (RTFNA) of pancreatic lesions can be performed.
      METHODS: Forty-five patients with pancreatic lesions (22 males and 23 females)
      underwent staging with the Olympus EUM-20 (Olympus America Corp, Melville, NY)
      followed by EUS-RTFNA with the Pentax FG-32PUA (Pentax-Precision Instrument Corp,
      Orangeburg, NY) and the 22-gauge GIP needle (GIP Medizin Technik, Grassau,
      Germany). RESULTS: EUS tumor stages were as follows: TO, n = 1; T1, n = 8; T2, n
      = 9; and T3 n = 27. Aspiration attempts were unsuccessful in four patients (two
      technical failures and two inadequate specimens). The remaining 41 lesions (mean
      size, 3.3 cm) were aspirated under EUS guidance (median passes, three) and the
      cytologic diagnoses were 25 definite adenocarcinoma, five suspicious for
      adenocarcinoma (three subsequently confirmed and two clinical course consistent
      with adenocarcinoma), and 11 negative for malignancy. Of 11 negatives, two were
      found to have adenocarcinoma, seven were confirmed benign at surgery (four
      cystadenomas and three inflammatory), one had a benign pseudocyst, and one had
      abundant inflammatory cells on RTFNA and follow-up time greater than 12 months
      with computed tomographic (CT) scans consistent with resolving inflammation.
      There were no false-positive RTFNAs. There were no procedure-related
      complications. Among those with diagnostic EUS-RTFNA (91%), the sensitivity for
      malignancy (confirmed plus suspicious) was 94% and negative predictive value 82%.
      CONCLUSION: EUS-guided RTFNA is a safe and accurate method for performing
      pancreatic biopsy. It should be considered in patients with suspected pancreatic
      malignancies in whom a tissue diagnosis is required or when other modalities have
      failed. EUS-RTFNA allows for local staging and tissue diagnosis in one procedure.

PMID- 9193338
TI  - Sexuality and fertility in long-term survivors of testicular cancer.
AB  - PURPOSE: We assessed the impact of different treatment modalities on sexuality
      and fertility in long-term survivors of testicular cancer. MATERIALS AND METHODS:
      The sample consisted of 85 testicular cancer patients, of whom 19 had undergone
      chemotherapy with retroperitoneal lymph node dissection (RPLND), 15 had received
      chemotherapy only, 42 had received infradiaphragmatic radiotherapy, and nine had
      received surveillance therapy. The questionnaire reported sexual function,
      marital status, and issues related to fertility and childbearing. RESULTS: One
      fourth to one half reported some type of sexual impairment in each group. The
      only significant difference was that approximately 70% of men with RPLND reported
      inability of ejaculation and a greater decline in semen volume, which is
      expected. The most striking finding is that the rates and nature of sexual
      dysfunction of surveillance patients were similar to other treatment groups,
      except for ejaculatory function. The highest rates of infertility distress were
      observed in chemotherapy patients. CONCLUSION: These data suggest that sexual
      dysfunction and infertility represent the major persisting side effects, even
      years after diagnosis. The hypothesis that surveillance patients have fewer
      sexual problems is not upheld in this study.

PMID- 9193339
TI  - Treatment of brain metastases in patients with testicular cancer.
AB  - PURPOSE: Despite improved cure rates for patients with metastatic testicular
      cancer with cisplatin-based combination chemotherapy, patients who develop brain
      metastases are generally considered to possess a poor prognosis. This report
      summarizes the long-term results in 44 patients with brain metastases from
      testicular cancer treated between 1978 and 1995 at Hannover University Medical
      School. PATIENTS AND METHODS: Histologically, 42 patients (95%) had a
      nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine
      patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for
      advanced disease according to the Indiana University classification even without
      considering the brain metastases. Eighteen patients (41%) presented with brain
      metastases at primary diagnosis (group 1), four (9%) developed brain metastases
      at relapse after a previous favorable response to combination chemotherapy (group
      2), and 22 (50%) developed brain metastases during or directly after cisplatin
      based chemotherapy. Chemotherapy consisted of cisplatin-based combination
      treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy
      and in single cases combined with a boost of 10 Gy to single lesions. RESULTS:
      Overall, 10 patients achieved long-term survival (23%; 95% confidence interval
      [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in
      groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive,
      compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with
      either chemotherapy or radiotherapy alone did not achieve long-term survival,
      while nine of 28 (32%) who received treatment with both modalities with or
      without surgery achieved sustained long-term survival. During univariate
      analysis, patients with the diagnosis of brain metastases at first presentation
      (P < .01), patients with a single brain lesion (P < .02), and patients who
      received combined chemotherapy and radiotherapy (P < .03) had a significantly
      improved outcome. CONCLUSIONS: Long-term survival can be achieved in
      approximately 25% of patients with brain metastases from testicular cancer by
      combined treatment with brain irradiation and aggressive cisplatin-based
      chemotherapy. Patients who develop brain metastases during systemic treatment
      should receive only palliative radiation therapy, since sustained survival will
      not be reached.

PMID- 9193341
TI  - Prostate-specific antigen failure despite pathologically organ-confined and
      margin-negative prostate cancer: the basis for an adjuvant therapy trial.
AB  - PURPOSE: A multivariable analysis to evaluate the potential clinical and
      pathologic factors that predict for early biochemical failure in patients with
      pathologically organ-confined and margin-negative disease was performed to define
      patients who may benefit from adjuvant therapy. PATIENTS AND METHODS: Three
      hundred forty-one prostate cancer patients treated with a radical retropubic
      prostatectomy between January 1989 and June 1995 and found to have pathologically
      organ-confined and margin-negative disease comprised the study population. A
      logistic regression multivariable analysis to evaluate the predictive value of
      the preoperative prostate-specific antigen (PSA) level, pathologic
      (prostatectomy) Gleason score, and pathologic stage on PSA failure occurring
      during the first postoperative year was performed. RESULTS: Predictors of PSA
      failure during the first postoperative year in patients with pathologically organ
      confined disease included pathologic Gleason score > or = 7 (P = .0007) and
      preoperative PSA level greater than 10 (P < .0001). Corresponding 3-year freedom
      from-PSA-failure rates for these pathologic organ-confined patients with both,
      one, or neither of these factors were 60%, 75% to 84%, and 95%, respectively (P <
      .0001). CONCLUSION: Prostate cancer patients with pathologically organ-confined
      and margin-negative disease and a preoperative PSA level greater than 10 ng/mL or
      a pathologic Gleason score > or = 7 have significant decrements in short-term PSA
      failure-free survival. Therefore, these patients should be considered for
      adjuvant therapy in the setting of a phase III clinical trial.

PMID- 9193340
TI  - Decision analysis for avoiding postchemotherapy surgery in patients with
      disseminated nonseminomatous germ cell tumors.
AB  - PURPOSE: This retrospective study was undertaken to assess the outcome of
      patients with disseminated nonseminomatous germ cell tumor (NSGCT) managed under
      a postchemotherapy strategy developed at Indiana University. PATIENTS AND
      METHODS: This is a retrospective analysis of 295 consecutive patients with
      disseminated NSGCT treated with primary chemotherapy at Indiana University from
      1987 to 1994. The patients were placed into five groups based on response to
      primary chemotherapy and the presence or absence of teratoma in the primary
      tumor. The 295 patients were divided as follows: group A (complete remission
      [CR]) n = 78; group B (unresectable), n = 50; group C (serologic CR, teratoma
      positive primary tumor, resectable partial remission [PR]), n = 90; group D
      [serologic CR, teratoma-negative primary tumor, < 90% radiographic PR], n = 50;
      and group E (serologic CR, teratoma-negative primary tumor, > or = 90%
      radiographic PR), n = 27. Groups A, B, and E patients were routinely observed
      after chemotherapy, whereas groups C and D patients were routinely taken to
      postchemotherapy surgery. RESULTS: The percent of patients who continuously had
      no evidence of disease (NED) were as follows: group A, 92%; group B, 40%; group
      C, 87%; group D, 86%; and group E, 74%. In assessing group A patients, the bulk
      of retroperitoneal disease at presentation had no influence on ultimate outcome.
      CONCLUSION: Patients with NSGCT who achieve a serologic and radiographic CR with
      primary chemotherapy (group A) can be safely observed without surgical
      intervention, regardless of initial tumor bulk. Patients with a teratoma-negative
      primary tumor who achieve a serologic CR and a > or = 90% radiographic remission
      and are followed-up without surgical resection (group E) are at an increased risk
      of relapsed NSGCT. Decisions about postchemotherapy resection in this group
      remain complicated and controversial. Options include observation with serial
      radiologic evaluation or surgical resection of persistent mass or masses.

PMID- 9193342
TI  - Phase II trial of suramin, leuprolide, and flutamide in previously untreated
      metastatic prostate cancer.
AB  - PURPOSE: To assess the efficacy and toxicity of suramin, hydrocortisone,
      leuprolide, and flutamide in previously untreated metastatic prostate cancer.
      PATIENTS AND METHODS: Patients with stage D2 and poor-prognosis stage D1 prostate
      cancer were given suramin on a pharmacokinetically derived dosing schedule to
      maintain suramin concentrations between 175 and 300 micrograms/mL. Additionally,
      all patients received flutamide 250 mg orally three times daily, initiated on day
      1 and continued until disease progression; depot leuprolide 7.5 mg
      intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and
      replacement doses of hydrocortisone. RESULTS: Fifty patients were entered onto
      the study: 48 with stage D2 and two with stage D1 disease. The median age was 59
      years (range, 42 to 79) and 31 patients had a Karnofsky performance status (KPS)
      of 100%. Forty-five patients had bone metastases and 25 had measurable soft
      tissue disease. Forty-one (82%) had severe disease. The overall response rate in
      49 assessable patients was three complete responses (CRs) and 30 partial
      responses (PRs) for an overall response rate of 67%. Eighteen patients have died.
      The median survival time has not been reached, with a median potential follow-up
      duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was
      predominantly hematologic and reversible. CONCLUSION: The high response rate and
      prolonged survival in a poor-prognosis group of patients with metastatic prostate
      cancer warrant a phase III randomized comparison of this regimen versus hormonal
      therapy alone. Toxicity was moderate and reversible.

PMID- 9193343
TI  - Family history of prostate cancer in patients with localized prostate cancer: an
      independent predictor of treatment outcome.
AB  - PURPOSE: To determine if familial prostate cancer patients have a less favorable
      prognosis than patients with sporadic prostate cancer after treatment for
      localized disease with either radiotherapy (RT) or radical prostatectomy (RP).
      PATIENTS AND METHODS: One thousand thirty-eight patients treated with either RT
      (n = 583) or RP (n = 455) were included in this analysis. These patients were
      noted as having a positive family history if they confirmed the diagnosis of
      prostate cancer in a first-degree relative. The outcome of interest was
      biochemical relapse-free survival (bRFS). We used proportional hazards to analyze
      the effect of the presence of family history and other potential confounding
      variables (ie, age, treatment modality, stage, biopsy Gleason sum [GS], and
      initial prostate-specific antigen [iPSA] levels) on treatment outcome. RESULTS:
      Eleven percent of all patients had a positive family history. The 5-year bRFS
      rates for patients with negative and positive family histories were 52% and 29%,
      respectively (P < .001). The potential confounders with bRFS rates were iPSA
      levels, biopsy GS, and clinical tumor stage; treatment modality and age did not
      appear to be associated with outcome. After adjusting for potential confounders,
      family history of prostate cancer remained strongly associated with biochemical
      failure. CONCLUSION: This is the first study to demonstrate that the presence of
      a family history of prostate cancer correlates with treatment outcome in a large
      unselected series of patients. Our findings suggest that familial prostate cancer
      may have a more aggressive course than nonfamilial prostate cancer, and that
      clinical and/or pathologic parameters may not adequately predict this course.

PMID- 9193344
TI  - Phase I pharmacokinetic study of multicycle high-dose carboplatin followed by
      peripheral-blood stem-cell infusion in patients with cancer.
AB  - PURPOSE: To examine the feasibility of escalating carboplatin area under the
      concentration-time curve (AUC), using dose predictions based on individual
      estimates of drug clearance, in a phase I trial of multicycle carboplatin,
      paclitaxel, and cyclophosphamide chemotherapy with peripheral-blood stem-cell
      (PBSC) replacement. PATIENTS AND METHODS: Forty-four patients (37 breast, seven
      ovarian) received 165 courses. Initial target carboplatin AUC was 10 mg/ml x min,
      with interpatient escalation in increments of 25%. Initial carboplatin dose
      estimates used creatinine clearance (CrCl) to estimate carboplatin clearance.
      Subsequent clearance and dose estimates were determined using a model
      incorporating Bayesian estimation and two measured carboplatin plasma
      ultrafiltrate concentrations. RESULTS: Median clearance was 80.5 mL/min/m2
      (range, 41.6 to 131.8). Carboplatin doses up to 2,440 mg/m2 per course were
      administered without major extramedullary toxicity. Doses varied 2.6-fold at each
      exposure level. Using the Bayesian model, AUC was predicted with a mean accuracy
      of 101.2% (83% using CrCl). Ninety-six of 117 courses were within 25% of the
      target AUC. This model was less biased (0.15 v -2.35 mg/mL x min) and more
      precise (2.76 v 3.52) in predicting AUC compared with one using CrCl. Hematologic
      recovery was not prolonged with increasing exposure. The carboplatin maximum
      tolerated systemic exposure (MTSE) was 13.3 mg/mL x min (level five). The dose
      limiting toxicity was cardiac toxicity, which occurred at dose levels six and
      seven. CONCLUSION: Results demonstrate that (1) CrCl is a poor estimator of
      carboplatin clearance in this population, and (2) the use of a model
      incorporating limited sampling and Bayesian estimation improves the precision of
      carboplatin clearance estimation and is suitable for targeting carboplatin
      exposure in an ambulatory setting.

PMID- 9193345
TI  - Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9
      aminocamptothecin in adult cancer patients.
AB  - PURPOSE: To investigate the pharmacokinetics and pharmacodynamics of 9
      aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74
      micrograms/m2/h. PATIENTS AND METHODS: 9-AC lactone and total (lactone plus
      carboxylate) plasma concentrations were measured in 44 patients with solid tumors
      using a high-performance liquid chromatography (HPLC) assay. Fifteen patients
      underwent extended pharmacokinetic sampling to determine the distribution and
      elimination kinetics of 9-AC. RESULTS: At steady-state, 8.7% +/- 4.7% (mean +/-
      SD) of the total drug circulated in plasma as the active 9-AC lactone. Clearance
      of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m2) over the entire dose range
      examined; however, total 9-AC clearance was nonlinear and increased at higher
      dose levels. In 15 patients treated at dose levels > or = 47 micrograms/m2/h, the
      volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m2 and
      for total 9-AC it was 23.6 +/- 10.6 L/m2. The elimination half-life was 4.47 +/-
      0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In
      pharmacodynamic studies, dose-limiting neutropenia correlated with steady-state
      lactone concentrations (Css) R2 = .77) and drug dose (R2 = .71). CONCLUSION:
      Plasma 9-AC concentrations rapidly declined to low levels following the end of a
      72-hour infusion and the mean fraction of total 9-AC circulating in plasma as the
      active lactone was less than 10%. The pharmacokinetics of 9-AC may have a great
      impact on its clinical activity and should be considered in the design of future
      clinical trials of this topoisomerase I inhibitor.

PMID- 9193346
TI  - Pharmacokinetic and pharmacodynamic evaluation of the topoisomerase inhibitor
      irinotecan in cancer patients.
AB  - PURPOSE: We conducted a pharmacokinetic and pharmacodynamic evaluation of
      irinotecan (CPT-11) and determined the effect of race and sex on disposition and
      toxicity of CPT-11. We tested the efficacy of acetaminophen (AAP) to phenotype SN
      38 glucuronidation. PATIENTS AND METHODS: Forty patients received a dose of 145
      mg/m2 of CPT-11 as a 90-minute infusion. Total CPT-11, SN-38, and SN-38G were
      quantitated in plasma and urine samples. Following administration of 1 g AAP,
      urinary concentrations of AAP and AAP-glucuronide (AAP-G) were assessed. RESULTS:
      CPT-11 exhibited a mean elimination half-life (t1/2) of 8.8 hours, an average
      clearance (CL) of 14.6 L/h/m2, and a mean volume of distribution at steady-state
      (Vdss) of 136 L/m2. SN-38 and SN-38G had low plasma availabilities (3% and 10%
      relative to CPT-11), with mean t1/2 values of 11.6 and 10.5 hours, respectively.
      Urinary recovery accounted for 15% of the dose. Race and sex had no effect on the
      plasma availability of CPT-11, SN-38, and SN-38G. The applicability of biliary
      index (BI) in predicting dose-limiting intestinal toxicity was validated.
      Patients who developed grade 3 or 4 toxicity had significantly higher index
      values compared with patients with grade 0 to 2 toxicity (P = .001). There was no
      difference in the incidence and severity of toxicity based on race and sex. AAP
      was a poor predictor of SN-38 glucuronidation. CONCLUSION: The high degree of
      interpatient variability in parameter estimates suggests pharmacogenetic
      variation or differential induction or inhibition of the sequential metabolic
      pathway of CPT-11, as well as variability in transport systems. The low urinary
      recovery indicates substantial biliary excretion and supports the significant
      correlation between intestinal toxicity and BI. Black patients are not at
      increased risk of toxicity. An assessment of individual differences in SN-38
      conjugation remains to be established.

PMID- 9193347
TI  - Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from
      fluorouracil in patients with advanced cancer.
AB  - PURPOSE: We performed a phase I study to determine the appropriate dose of PN401,
      a uridine (URD) prodrug, to use as a rescue agent for fluorouracil (FU) and than
      to determine the maximum-tolerated dose (MTD) of FU when given with PN401.
      PATIENTS AND METHODS: Patients with advanced cancer received oral PN401 as either
      a suspension or a tablet in escalating doses. A pharmacokinetic analysis was
      performed to determine which dose best achieved a target value of sustained
      levels of URD > or = 50 mumol/L. In the first phase of the study, all patients
      received a fixed dose of FU 600 mg/m2 as a rapid intravenous bolus followed by 10
      doses of PN401 given at 6-hour intervals. PN401 therapy commenced 24 hours after
      FU. After determination of the appropriate dose of PN401, a second group of
      patients received escalating doses of FU with a fixed dose of PN401. RESULTS:
      Thirty-eight patients with advanced cancer received PN401 and FU. Pharmacokinetic
      analysis indicated that either 6.6 g of PN401 as an oral suspension or 6 g given
      in tablet form resulted in high bioavailability of URD, with sustained plasma
      concentrations greater than 50 mumol/L. In the second phase of the study, FU
      doses were escalated from 600 to 1,000 mg/m2. FU was given as a rapid intravenous
      bolus weekly for 6 weeks with a 2-week rest. The MTD of FU given in this fashion
      with PN401 rescue was 1,000 mg/m2, at which level two of six patients had
      neutropenic fever. FU at doses of 800 mg/m2 for 6 weeks was well tolerated
      without significant toxicity when given with PN401 rescue. CONCLUSION: Oral PN401
      is well tolerated and total doses of 6 g every 6 hours yield sustained levels of
      URD in the target range of 50 mumol/L. The MTD of FU with PN401 rescue is 1,000
      mg/m2 and the recommended dose for phase II trials is 800 mg/m2 given weekly for
      6 weeks with dose escalation. Further studies to define better the appropriate
      interval for PN401 rescue and the appropriate dose of FU when given with
      biochemical modulation, such as with leucovorin, are indicated.

PMID- 9193348
TI  - High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients
      with gastrointestinal cancers: a phase I trial.
AB  - PURPOSE: A phase I trial that evaluated for extrahematopoietic toxicity was
      conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49.
      Correlative studies included pharmacokinetic and biodistribution analyses,
      estimates of absorbed radiation dose, and measurement of human antimonoclonal
      antibodies (HAMA). PATIENTS AND METHODS: After collection and cryopreservation of
      hematopoietic stem cells, 15 patients with gastrointestinal cancers were
      administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two
      to three per activity level) underwent a single treatment with 131I-MAb CC49 (50,
      100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar
      and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic
      studies were performed by measuring radioactivity in serial blood samples. In
      some patients, biopsies of metastases and related normal tissues were obtained
      for radioactivity measurements. Radiation dosimetry estimates were calculated
      using available biodistribution, pharmacokinetic, and tissue biopsy data.
      Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity
      Criteria. RESULTS: No dose-limiting extrahematopoietic toxicity was identified.
      Twelve patients experienced grade IV myelosuppression and met criteria for
      infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The
      T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7
      +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per
      killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic
      tumor sites ranged from 630 to 3300 cGy. CONCLUSION: Although extrahematopoietic
      dose-limiting toxicity was neither observed or predicted, suboptimal absorbed
      dose estimates suggested that further escalation of 131I-MAb CC49 would not be
      useful. Future studies should focus on the use of radionuclides with high energy
      beta emissions, such as yttrium 90, and on strategies to optimize access of
      antibody to target antigens.

PMID- 9193349
TI  - Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal
      antibody G250.
AB  - PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging
      characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb)
      G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to
      determine the therapeutic potential of this antibody. PATIENTS AND METHODS:
      Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi
      131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg).
      Planar scintigraphic images were acquired, and normal tissue biopsies and tumor
      samples were obtained of surgery (7 days postinjection). The immunogenicity of
      cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA)
      and dosimetric analysis was performed. RESULTS: In all patients with antigen
      positive tumors (n = 13), the primary tumors and all known metastases were
      clearly visualized. Overall uptake, expressed as the percentage of the injected
      dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250
      uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was
      highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low.
      Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary
      tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A
      bone metastasis received .23 Gy/mCi and regional lymph node metastases received
      .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in
      two of 16 patients. CONCLUSION: 131I-cG250 tumor uptake is among the highest
      reported in clinical studies with antitumor antibodies in solid tumors. Since
      tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250
      are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a
      promising vehicle for radioimmunotherapy in RCC.

PMID- 9193350
TI  - Phase I trial of docetaxel administered as a 1-hour infusion in children with
      refractory solid tumors: a collaborative pediatric branch, National Cancer
      Institute and Children's Cancer Group trial.
AB  - PURPOSE: A phase I trial of docetaxel was performed to determine the maximum
      tolerated dose (MTD), the dose-limiting toxicities, and the incidence and
      severity of other toxicities in children with refractory solid tumors. PATIENTS
      AND METHODS: Forty-four children received 103 courses of docetaxel administered
      as a 1-hour intravenous infusion every 21 days. Doses ranged from 55 to 150
      mg/m2, MTD was defined in heavily pretreated and less heavily pretreated (< or =
      2 prior chemotherapy regimens, no prior bone marrow transplantation [BMT], and no
      radiation to the spine, skull, ribs, or pelvic bones) patients. RESULTS: Dose
      related neutropenia was the primary dose-limiting toxicity. The MTD in the
      heavily pretreated patient group was 65 mg/m2, but the less heavily pretreated
      patients tolerated a significantly higher dose of docetaxel (maximum-tolerated
      dose, 125 mg/m2). Neutropenia and constitutional symptoms consisting of malaise,
      myalgias, and anorexia were the dose-limiting toxicities at 150 mg/m2 in the less
      heavily pretreated patients. Thrombocytopenia was not prominent, even in patients
      who experienced dose-limiting neutropenia. Common nonhematologic toxicities of
      docetaxel included skin rashes, mucositis, and mild elevations of serum
      transaminases. Neuropathy was uncommon. Peripheral edema and weight gain were
      observed in two of five patients who received more than three cycles of
      docetaxel. A complete response (CR) was observed in one patient with
      rhabdomyosarcoma, a partial response (PR) in one patient with peripheral
      primitive neuroectodermal tumor (PPNET), and a minimal response (MR) in two
      patients with PPNET. Three of the four responding patients were treated at doses
      > or = 100 mg/m2. CONCLUSION: The recommended phase II dose of docetaxel
      administered as a 1-hour intravenous infusion in children with solid tumors in
      125 mg/m2. Because neutropenia was the dose-limiting toxicity and
      thrombocytopenia was mild, further escalation of the dose should be attempted
      with granulocyte colony-stimulating factor (G-CSF) support.

PMID- 9193351
TI  - Clinical cardiotoxicity following anthracycline treatment for childhood cancer:
      the Pediatric Oncology Group experience.
AB  - PURPOSE: To determine the incidence of clinical cardiotoxicity from anthracycline
      chemotherapy in children with cancer and to identify associated risk factors.
      PATIENTS AND METHODS: The study population consisted of 6,493 children with
      cancer who had received anthracycline chemotherapy on Pediatric Oncology Group
      (POG) protocols from 1974 to 1990. Cardiotoxicity, defined as congestive heart
      failure not due to other causes, abnormal measurements of cardiac function that
      prompted discontinuation of therapy, or sudden death from presumed cardiac
      causes, was determined by a review of protocol records. RESULTS: Cardiotoxicity
      was confirmed in 106 patients (1.6%): 58 had congestive heart failure, 43 had
      changes in measures of cardiac function that prompted the discontinuation of
      therapy, and five died suddenly from presumed cardiac causes. In a multivariate
      analysis, factors that contributed to the relative risk (RR) of toxicity were a
      cumulative anthracycline dose > or = 550 mg/m2 of body-surface area (RR = 5.2),
      maximal dose > or = 50 mg/m2 (RR = 2.8), female sex (RR = 1.9), black race (RR =
      1.7), presence of trisomy 21 (RR = 3.4), and exposure to amsacrine (RR = 2.6).
      Cardiotoxicity within 1 year after the completion of anthracycline treatment
      (early cardiotoxicity) represented 89.5% of all cases. CONCLUSION: Early clinical
      cardiotoxicity in children treated with anthracycline is rare. A high maximal
      dose, or cumulative dose of anthracycline, female sex, black race, presence of
      trisomy 21, and treatment with amsacrine increase the risk for anthracycline
      associated cardiotoxicity.

PMID- 9193352
TI  - Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's
      sarcoma of the extremities.
AB  - PURPOSE: This study was performed to assess the prognostic value of the proposed
      histopathologic method to evaluate the response of the primary tumor to
      preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response
      to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients,
      who were preoperatively treated by chemotherapy alone. Responses were graded I to
      III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor
      cells, respectively). Follow-up data were available for all patients, with a mean
      follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically
      highly significant difference was observed in outcome among the three groups of
      patients. For patients with total necrosis (grade III response), the estimated 5
      year disease-free survival rate was 95%, in contrast to 68% for grade II
      responders and 34% for grade III responders (P < .0001). This difference was also
      confirmed when any single group was compared with the other groups. Among the
      parameters tested, patient age and the size of tumor had some prognostic value.
      CONCLUSION: The proposed histopathologic grading, to evaluate the effect of
      chemotherapy on the primary tumor, had the strongest correlation to clinical
      outcome. This method could therefore be used to identify patients with a high
      risk of recurrent disease. These patients could be randomized to receive
      alternative postoperative treatments to investigate whether more aggressive
      therapies will improve outcome.

PMID- 9193353
TI  - Serum aminotransferase elevation during and following treatment of childhood
      acute lymphoblastic leukemia.
AB  - PURPOSE: The clinical significance of methotrexate (MTX)-induced hepatic toxicity
      in children with acute lymphoblastic leukemia (ALL) is poorly defined. Therefore,
      we conducted a study to determine whether intensive MTX therapy could be safely
      delivered despite isolated serum ALT elevations in children with ALL. PATIENTS
      AND METHODS: A total of 243 children with B-precursor ALL were treated with
      extended pulses of oral divided-dose MTX (dMTX). Serum ALT levels were measured
      approximately every 7 weeks during therapy, as well as after its cessation. By
      protocol design, treatment was continued without modification in the presence of
      ALT elevations if there was no other evidence of liver dysfunction. RESULTS: Of
      239 assessable patients, 159 (66.5%) had an ALT level > or = 180 IU/L during
      therapy and 28 patients (17.6%) had one or more values > or = 720 IU/L. After the
      completion of therapy, only 17 of 104 assessable patients have had one or more
      elevated ALT value. Eight of these 17 patients (47%) are hepatitis C virus (HCV)
      seropositive. The remaining nine children had subsequent normal or near normal
      ALT values, and none have clinical evidence of liver disease. CONCLUSION: Our
      data show that MTX can be safely delivered without dose modification in patients
      with isolated ALT elevations and that continued therapy does not lead to
      clinically apparent liver disease. ALT elevations are not a reliable predictor of
      the presence or extent of hepatic injury, and persistently increased ALT values
      following the completion of ALL therapy are rare in the absence of HCV infection.
      Continued MTX therapy allows for increased dose-intensity and may improve outcome
      in children with ALL.

PMID- 9193354
TI  - Phase II multicenter study of human CD52 antibody in previously treated chronic
      lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic
      Lymphocytic Leukemia.
AB  - PURPOSE: CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal
      antibody (MAb) that binds to nearly all B- and T-cell lymphomas and leukemias. We
      report the results of a multicenter phase II trial that used CAMPATH-1H in
      previously chemotherapy-treated patients with chronic lymphocytic leukemia (CLL).
      MATERIALS AND METHODS: Twenty-nine patients who had relapsed after an initial
      response (n = 8) or were refractory (n = 21) to chemotherapy were treated with
      CAMPATH-1H administered as a 30-mg 2-hour intravenous (IV) infusion thrice weekly
      for a maximum period of 12 weeks. RESULTS: Eleven patients (38%) achieved a
      partial remission (PR) and one (4%) a complete remission (CR) (response rate,
      42%; 95% confidence interval [CI], 23% to 61%). Three of eight patients (38%)
      with a relapse and nine of 21 refractory patients (43%) responded to CAMPATH-1H
      therapy. CLL cells were rapidly eliminated from blood in 28 of 29 patients (97%).
      CR in the bone marrow was obtained in 36% and splenomegaly resolved completely in
      32%. Lymphadenopathy was normalized in only two patients (7%). The median
      response duration was 12 months (range, 6 to 25+). World Health Organization
      (WHO) grade IV neutropenia and thrombocytopenia developed in three (10%) and two
      patients (7%), respectively. Neutropenia and thrombocytopenia recovered in most
      responding patients during continued CAMPATH-1H treatment. Lymphopenia (< 0.5 x
      10(9)/L) occurred in all patients. Two patients had opportunistic infections and
      four had bacterial septicemia. CONCLUSION: CAMPATH-1H had significant activity in
      patients with advanced and chemotherapy-resistant CLL. The most pronounced
      effects were noted in blood, bone marrow, and spleen. Preferential clearance of
      blood may allow harvesting of uncontaminated blood stem cells for use in high
      dose chemotherapy protocols.

PMID- 9193355
TI  - Mobilization and transplantation of Philadelphia-negative peripheral-blood
      progenitor cells early in chronic myelogenous leukemia.
AB  - PURPOSE: Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now
      possible in many Ph1-positive chronic myelogenous leukemia (CML) patients who had
      received interferon alfa (IFN-alpha) with no cytogenetic response. In this pilot
      study, we used this approach in patients without prior IFN-alpha therapy to
      determine if the number and quality of mobilized progenitors would be increased
      and to evaluate the potential effect of these cells as autografts. PATIENTS AND
      METHODS: Twenty-two untreated patients were mobilized within 12 months of
      diagnosis. The treatment regimen consisted of the mini-ICE protocol. Beginning on
      day +8, granulocyte colony-stimulating factor (G-CSF) was used in all patients.
      Leukophoresis was performed as the patients were recovering from aplasia, when
      WBC count exceeded 0.8 x 10(9)/L. RESULTS: In 14 patients, (63%) the
      leukophoresis product was entirely Ph1-negative and in four patients the Ph1
      positive cell rate was < or = 7%. Significant numbers of long-term culture
      initiating cells (LTC-IC) and CD34+ Thy1+Lin- cells were found in most of the Ph1
      negative collections that were tested. Twelve patients underwent autografting
      with their mobilized peripheral-blood progenitor cells (PBPC) (Ph1-negative
      collections, 10 patients; major cytogenetic response, two patients). All patients
      engrafted and are alive; six have Ph1-negative marrow 7 to 15 months after
      autografting. Posttransplant treatment was IFN-alpha combined with interleukin
      (IL)-2 because of the recent demonstration of synergistic activity in augmenting
      cytolytic activity. CONCLUSION: Intensive chemotherapy given in early chronic
      phase of CML is well tolerated and results in high numbers of circulating Ph1
      negative precursor cells.

PMID- 9193356
TI  - Secondary acute myelogenous leukemia following safe exposure to etoposide.
AB  - PURPOSE: To present two patients as illustrations of the risk of developing
      secondary acute myelogenous leukemia (sAML) when theoretically safe doses of
      etoposide (VP-16) are used. PATIENTS AND METHODS: Patient no. 1 was a 15-year-old
      white girl diagnosed with stage IIa Hodgkin's disease. She was treated with a
      combination of vincristine, doxorubicin, bleomycin, and VP-16 (2 g/m2 total) over
      4 months, followed by 25.5 Gy of involved-field radiotherapy. Patient no. 2 was
      an 11-year-old white boy diagnosed with virus-associated hemophagocytic syndrome
      (VAHS). He was treated with VP-16 intravenously (IV) and orally (0.3 g and 2.8
      g/m2, respectively). RESULTS: Patient no. 1 developed AML 16 months from the
      diagnosis of Hodgkin's disease. Patient no. 2 developed AML 26 months from
      diagnosis. Both bone marrows were consistent with French-American-British (FAB)
      M4 disease. Both patients had abnormalities of the long arm of chromosome 11.
      CONCLUSION: The use of low-dose or oral VP-16 can be associated with the
      development of sAML. Clinicians should be cautious in the use of VP-16 in low
      risk diseases.

PMID- 9193357
TI  - Incidence, predictive factors, and outcome of lymphoma transformation in
      follicular lymphoma patients.
AB  - PURPOSE: To assess the incidence of lymphoma transformation in the natural
      history of follicular lymphoma (FL) patients and the factors that are predictive
      of this event. PATIENTS AND METHODS: Two hundred twenty patients with FL treated
      in our institution between 1975 and 1990, with a median follow-up duration of 9
      years, were included in this retrospective analysis. RESULTS: Transformation was
      proven by histology in 34 patients or by cytology in 13 patients and was
      considered as highly probable on clinical arguments in five patients for an
      overall incidence of 24%. The probability of transformation was 22% at 5 years
      and 31% at 10 years and tended to plateau after 6 years. Predictive factors for
      transformation were nonachievement of complete remission (CR) after initial
      therapy (P < 10(-4), low serum albumin level (< 35 g/L) (P = .001), and beta 2
      microglobulin level greater than 3 mg/L (P = .02) at diagnosis. In a
      multiparametric analysis, only beta 2-microglobulin level retained prognostic
      significance for freedom-from-transformation (FFT) survival (P = .04).
      Transformation accounted for 44% of deaths and was associated with a poor
      outcome, with a median survival time of 7 months. CONCLUSION: Transformation is
      an early event in the course of the disease and is mainly observed in patients
      with known adverse prognostic factors or those who do not achieve CR after
      initial treatment. These findings may be useful to select follicular lymphoma
      patients for intensive therapeutic approaches.

PMID- 9193358
TI  - Role of a second transplant in the management of poor-prognosis lymphomas: a
      report from the European Blood and Bone Marrow Registry.
AB  - PURPOSE: Treatment of selected patients with poor-prognosis lymphomas with high
      dose chemotherapy and marrow or peripheral stem-cell rescue improves prognosis. A
      second course of myeloablative chemotherapy has been given to some patients, but
      few data are available on the indications, morbidity, and overall survival
      associated with this approach. This study was undertaken to evaluate morbidity
      and identify subgroups of patients who may benefit from a second transplant.
      PATIENTS AND METHODS: Thirty-four patients with lymphoma given two cycles of
      myeloablative chemotherapy and entered onto the European Blood and Bone Marrow
      Transplant (EBMT) registry between 1982 and 1995 were included in this study:
      Hodgkin's disease (HD), n = 12; intermediate/high-grade non-Hodgkin's lymphoma
      (HG-NHL), n = 17; and low-grade non-Hodgkin's lymphoma (LG-NHL), n = 5. The
      reason for second transplant, status at transplant, conditioning regimen,
      morbidity, and both progression-free survival (PFS) and overall survival (OS)
      were assessed. RESULTS: The second procedure was performed for the following
      reasons: (1) elective double procedure in four patients, (2) relapse after first
      transplant in 20, (3) partial remission (PR) after first transplant in eight, and
      (4) refractory disease after first transplant in two. The OS rate at 2 years for
      patients who underwent two transplants (estimated from the date of second
      transplant) was 49%, with a median follow-up time of 44 months. The OS rate at 2
      years by histologic subtype was as follows; HD, 50%; HG-NHL, 60%; and LG-NHL, 0%.
      Seven of 15 patients with HD or HG-NHL who relapsed after they had achieved a
      posttransplant complete remission (CR) remain in CR 13 to 36 months after the
      second transplant, compared with two of 10 patients in CR (at 6 and 19 months
      after second transplant) who achieved a PR or had refractory disease after the
      first transplant. There were eight deaths (24%) before 3 months, of which three
      (9%) were transplant-related and the remainder due to persistent disease. Three
      late toxic deaths occurred: two of cardiovascular disease and one of secondary
      leukemia. CONCLUSION: Selected patients with HD and HG-NHL whose disease recurs
      after one transplant may benefit from a second transplant. Patients with
      refractory disease and LG-NHL did not benefit from a second transplant.

PMID- 9193359
TI  - Allogeneic-blood stem-cell collection following mobilization with low-dose
      granulocyte colony-stimulating factor.
AB  - PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for
      mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined.
      As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched
      donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous
      administration. The purpose of this trial was to monitor adverse effects during G
      CSF administration and stem-cell collection, to determine the optimal timing for
      stem-cell collection, and to determine the cellular composition of stem-cell
      products following G-CSF administration. PATIENTS AND METHODS: The median donor
      age was 42 years. Apheresis began on day 4 of G-CSF administration. At least
      three daily 12-L apheresis collections were performed on each donor. A minimum of
      1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear
      cells/kg were collected from each donor. All collections were cryopreserved in 5%
      dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated
      with G-CSF administration and the apheresis process included myalgias/arthralgias
      (83%), headache (44%), fever (27%), and chills (22%). The median baseline
      platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on
      days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+
      cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg,
      respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells
      remained relatively constant during the three collections. Median total numbers
      of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x
      10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient
      numbers of AlloBSC safely and efficiently.

PMID- 9193360
TI  - Hematopoietic recovery after allogeneic blood stem-cell transplantation compared
      with bone marrow transplantation in patients with hematologic malignancies.
AB  - PURPOSE: To compare hematopoietic recovery, duration of hospitalization, and 100
      day survival in patients who received allogeneic-blood stem cells (BSC) or
      conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS:
      From December 1994 to August 1995, 21 patients participated in a phase II study
      of allogeneic BSC transplantation. Cells mobilized with granulocyte colony
      stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human
      leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus
      host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF
      (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared
      with 22 identically treated historical patients who received allogeneic BMT.
      RESULTS: The median infused CD34+ cell and granulocyte-macrophage colony-forming
      unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The
      median time to a neutrophil count greater than 500/ microL was 11 days after BSC
      and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC
      recovery after BSC was observed. BSC patients received fewer platelet
      transfusions: 10 versus 19 (P = .015). The median length of hospitalization was
      shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day
      survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The
      incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT,
      respectively (P = .4654). CONCLUSION: In comparison to BMT, allogeneic BSC
      transplantation may result in faster hematopoietic recovery, shorter hospital
      stay, and similar early survival. Whether allogeneic BSC are superior to bone
      marrow needs to be determined in randomized trials.

PMID- 9193362
TI  - Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal
      lymphoma behavior: analysis of 108 patients.
AB  - PURPOSE: Characteristics and outcome of 108 patients with mucosa-associated
      lymphoid tissue (MALT) lymphoma were analyzed according to initial location of
      the lymphoma, within or outside of the gastrointestinal (GI) tract. PATIENTS AND
      METHODS: One hundred eight patients with MALT lymphoma were studied. Fifty-five
      patients (51%) had GI involvement and 53 patients (49%) had another involved
      extranodal site: 13 orbit; 11 lung; 10 skin; seven parotid; six thyroid; three
      Waldeyer's ring; two breast; and one pancreas involvement. At diagnosis, 47
      patients (44%) had stage IE, 26 (24%) had stage IIE, and 35 (32%) had
      disseminated disease. No significant difference in the clinical or biologic
      characteristics was observed between GI and non-GI patients. RESULTS: Complete
      response after the first treatment was reached in 76% of the patients, with no
      difference between the two subgroups. With a median follow-up of 52 months,
      median survival was not reached and was identical in the two subgroups, but GI
      MALT patients had a longer time to progression (8.9 years compared with 4.9 years
      in non-GI patients; P = .01). The different non-GI locations seemed to have a
      similar outcome. CONCLUSION: MALT lymphoma is an indolent disease that usually
      presents as localized extranodal tumor without accompanying adverse prognostic
      factor, and these patients have a good outcome. However, non-GI patients seem to
      progress more often than GI patients.

PMID- 9193361
TI  - Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein
      versus granulocyte-macrophage colony-stimulating factor after autologous bone
      marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double
      blind trial.
AB  - PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony
      stimulating factor (GM-CSF) following high-dose therapy and autologous bone
      marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic
      recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non
      Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321
      750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250
      micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT
      for a maximum of 28 days. RESULTS: The median time to reach an absolute
      neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus
      19 days in the GM-CSF group (P = .07) and the median time to reach platelet
      transfusion independence in the PIXY321 group was 25 days versus 23 days in the
      GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be
      equivalent with the exception of more patients in the PIXY321 group with a rash
      (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression
      model identified the use of a non-total-body irradiation (TBI) regimen and/or
      receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as
      predictive of faster neutrophil engraftment, and those three factors, as well as
      the receipt of < or = two prior chemotherapy regimens as predictive for rapid
      platelet engraftment. CONCLUSION: There was a trend toward a slight improvement
      in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route
      compared with GM-CSF administered by an IV route. However, no differences could
      be identified between the two agents with respect to the time to platelet
      transfusion independence. Patient, regimen, and graft characteristics were most
      predictive of the engraftment tempo.

PMID- 9193363
TI  - Early restaging gallium scans predict outcome in poor-prognosis patients with
      aggressive non-Hodgkin's lymphoma treated with high-dose CHOP chemotherapy.
AB  - PURPOSE: This prospective study assessed the predictive value of early restaging
      gallium (Ga) and computed tomographic (CT) scans in poor-prognosis patients with
      aggressive non-Hodgkin's lymphoma (NHL) who were treated with high-dose
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy.
      PATIENTS AND METHODS: Thirty newly diagnosed patients with bulky (> or = 10 cm)
      advanced-stage aggressive NHL were treated with a four-cycle high-dose CHOP
      regimen (22 patients at maximum-tolerated dose [MTD]: cyclophosphamide 4 g/m2,
      doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg orally for 5 days).
      All patients had chest/abdominal/pelvic CT scans and 10-mCi Ga scans at baseline
      and following two and four cycles of therapy. Scans were reviewed in a blinded
      manner for CT-documented rates of response and sizes of residual masses and Ga
      avidity of residual masses. The results of early (post-cycle 2) and final (post
      cycle 4) restaging were subsequently associated with clinical outcome. RESULTS:
      CT-documented rates of response and residual mass sizes were indistinguishable in
      complete responders who remained continuously disease-free (CR-Cont), complete
      responders who subsequently relapsed (CR-Rel), and partial responders who then
      progressed (PR/Prog). In marked contrast, early restaging (post-cycle 2) Ga scans
      accurately delineated these three categories of patients: CR-Cont 90% Ga-negative
      (18 of 20 patients) versus CR-Rel 25% Ga-negative (one of four patients) versus
      PR/Prog 0% Ga-negative (zero of six patients) (P = .000014). At a median follow
      up duration of 31 months (range, 21 to 46), 94% of patients who had negative
      early restaging Ga scans remain free from progression (FFP), whereas only 18% of
      patients who had positive early restaging Ga scans remain FFP (P = .000007).
      Early restaging Ga scans were more predictive for FFP than final restaging Ga
      scans because patients who required four full cycles of therapy to become Ga
      negative were more likely to develop recurrent disease. CONCLUSION: Early
      restaging Ga scans delineate patients who are likely to have prolonged disease
      free survival from those who fail to respond to intensive induction therapy.
      Patients whose tumors remain Ga-positive midway through high-dose CHOP therapy
      have a poor outcome and may be candidates for alternative treatment.

PMID- 9193365
TI  - Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell
      lymphoma: a multicenter study of 106 patients.
AB  - PURPOSE: To define clinicopathologic features, response to treatment, and
      prognostic factors of primary mediastinal B-cell lymphoma (MBL), a CD20+ tumor
      recognized as a distinct entity among non-Hodgkin's lymphomas (NHL). PATIENTS AND
      METHODS: One hundred six patients presented with disease confined to thorax
      (86%), bulky mediastinum (73%), superior vena cava syndrome (47%), and contiguous
      infiltration (57%). Ninety-nine received doxorubicin-containing chemotherapy
      (CHT). RESULTS: Thirty-five of 99 patients were primarily CHT-resistant, and 64
      responded: 23 achieved complete response (CR) and 41 achieved response with
      residual mediastinal abnormality. Seventy-seven percent of responders received
      mediastinal radiotherapy (RT). Of 64 responders, 18 (28%) relapsed: none of 23 CR
      patients and 18 of 41 (44%) with residual mediastinal abnormality. Relapse-free
      survival rate of responders was 71% at 3 years. Actuarial 3-year survival rate
      was 52% for all patients and 82% for responders. Predictive factors of poor
      outcome were identified by logistic regression; Cox survival analysis was
      performed on death and relapse. Pericardial effusion (P < .001) and Eastern
      Cooperative Oncology Group (ECOG) performance status > or = 2 (P = .009)
      predicted nonresponse (NR) and affected survival. Less than partial midway
      response to CHT predicted NR to subsequent therapies. Bulky disease was related
      to persistent mediastinal abnormality and risk of relapse (P = .025). CONCLUSION:
      MBL is an aggressive NHL with unique clinicopathologic aspects, often refractory
      to current CHT designed for high-grade NHL. Poor performance status and
      pericardial effusion predict NR and poor survival. Inadequate response after the
      first courses of front-line CHT predicts failure of subsequent treatment.
      Responders with bulky mediastinum or residual mediastinal abnormality after CHT
      are at risk of relapse. These factors should help to select high-risk patients
      for intensive treatments.

PMID- 9193366
TI  - Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis
      of 89 cases included in the LNH87 trial and comparison with the outcome of
      diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.
AB  - PURPOSE: The aims of this study were as follows: (1) to analyze clinical,
      histopathologic characteristics, treatment outcome, and prognostic factors of
      patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with
      those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same
      therapeutic trial. PATIENTS AND METHODS: Eighty-nine FLCL patients who were
      histologically reviewed and who received an intensive chemotherapy regimen
      according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell
      DLCL patients included in the same protocol. RESULTS: After intensive induction
      treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year
      survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%.
      Prognostic factors associated with shorter FFP were age greater than 60 years (P
      = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH)
      level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03),
      bone marrow involvement (P = .04), and high expression of bcl-2 protein (P =
      .05). When compared with B-cell DLCL patients, FLCL patients were younger (P =
      .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05),
      less bulky mass (P = .04), more advanced clinical stages (P < .001), and more
      bone marrow involvement (P = .02). No significant difference was observed between
      FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall
      survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival
      (39% v 43%). CONCLUSION: FLCL patients have a favorable response rate and
      survival when treated with intensive chemotherapy. Their outcome is similar to
      that of B-cell DLCL patients, and a long-term FFP is observed for a substantial
      number of patients. Some adverse prognostic factors (including those of the
      International Prognostic Index, bone marrow involvement, and beta-2
      microglobulin) have been identified to define a subset of patients who require
      other therapeutic approach.

PMID- 9193367
TI  - Mantle cell lymphoma: correlation of clinical outcome and biologic features with
      three histologic variants.
AB  - PURPOSE: Clinical data and histologic material were retrospectively analyzed in
      46 cases of previously untreated mantle cell lymphoma (MCL) to more fully
      characterize the clinical response pattern of these lymphomas and to determine
      whether growth pattern significantly affected clinical outcome. MATERIALS AND
      METHODS: The histologic pattern was classified as diffuse (61%), nodular (13%),
      and mantle zone (26%) in accordance with stated criteria. RESULTS: Bone marrow
      infiltration was detected in 69% of cases; the frequency of involvement
      correlated with histologic pattern, being most common in diffuse variants and
      least common in mantle zone variants. Other sites of extranodal involvement were
      observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of
      25 patients (92%) and no difference was observed between the various histologic
      patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was
      detected in seven of 21 cases, without regard for histologic pattern. Complete
      response rates to doxorubicin-based regimens showed a striking correlation with
      histologic pattern. Seventy-three percent of patients with a mantle zone pattern
      attained a complete response compared with only 25% of patients with a nodular
      pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%,
      and 55% for patients with mantle zone, nodular, and diffuse histologic patterns,
      respectively. CONCLUSION: We conclude that (1) diffuse and nodular MCL are
      associated with a poor treatment response and a poor overall survival rate; (2)
      the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma;
      and (3) the poor survival rates of patients with nodular and diffuse MCL suggest
      that these variants be classified as intermediate-grade lymphomas. However, the
      trend of the time to treatment failure curve does not indicate that current
      regimens can cure MCL.

PMID- 9193364
TI  - Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV
      hybrid regimen with alternating courses of MOPP and ABVD: a report from the
      National Cancer Institute of Canada clinical trials group.
AB  - PURPOSE: This randomized, prospective trial compares outcomes for patients with
      advanced Hodgkin's disease treated with mechlorethamine, vincristine,
      procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV)
      hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and
      dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's
      disease were randomized to receive MOPP/ ABV hybrid regimen or alternating
      MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment
      center. Eligible patients were either previously untreated and found to have
      stage IIIB, IVA, or IVB disease or previously treated with wide-field
      irradiation. Responding patients received a minimum of eight cycles of
      chemotherapy. Those with residual disease in a localized region received
      irradiation between the sixth and seventh cycle of treatment. RESULTS: Response
      rates to the two regimens were similar. Five-year overall survival rates were 81%
      and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74;
      95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure
      free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD,
      respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more
      episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV
      hybrid regimen; there was no significant difference in fatal toxicity. Patients
      with predefined, high-quality partial responses (PR-1s) had results similar to
      those with complete responses (CRs). Planned subset analysis showed no
      significant difference in outcome between the two arms of the trial for patients
      with newly diagnosed disease (5-year failure-free survival rates were 70% for
      MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of
      alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free
      survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating
      MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's
      disease.

PMID- 9193368
TI  - Patient preferences for interferon alfa in multiple myeloma.
AB  - PURPOSE: Interferon alfa treatment in multiple myeloma marginally improves
      relapse-free and overall survival. Often it does so at the expense of toxicity
      and financial cost. If patients are unwilling or unable to participate in the
      decision of whether to initiate such treatment, known patient preferences can
      serve as guidelines for the physician. We interviewed myeloma patients in the
      United States to obtain information that might facilitate medical decision
      making. PATIENTS AND METHODS: Three hundred fifty-five myeloma patients
      throughout the United States were interviewed by telephone. Without identifying
      interferon alfa as the treatment agent, interviewers described potential adverse
      effects, financial cost, and self-injection procedures. The potential benefits of
      four treatment choices, derived from a meta-analysis of published data, were
      presented as gains in remission rate (+10%), remission duration (an additional 4
      and 7 months, respectively, for induction and maintenance treatment), and overall
      survival (an additional 3 and 6 months, respectively, for induction and
      maintenance treatment). Patients' choices for or against use of the unidentified
      substance were recorded, and interferon was subsequently disclosed as the
      treatment. The profiles of patients making different choices were determined
      using multivariate regression techniques. RESULTS: Approximately half of the
      patients accepted the unidentified treatment if remission and/or survival
      improved by at least 6 months. Accepters were younger and more likely to have
      used interferon. Of patients who rejected the unidentified treatment, 25% to 50%
      would have been willing to accept it if the benefits were > or = 12 months.
      Test/retest reliability of all choices, determined in 36 cancer patients, was
      0.896. CONCLUSION: In multiple myeloma, interferon therapy and, by inference,
      other treatments with comparable features are acceptable to approximately half of
      the patients if a 6-month gain in relapse-free or overall survival can be
      expected.

PMID- 9193369
TI  - Socioeconomic status and cancer survival in Ontario.
AB  - BACKGROUND AND PURPOSE: It is known that the socioeconomic status (SES) of the
      patient is associated with cancer survival in the United States. The purpose of
      this study was to determine whether the association between SES and survival is
      also present in Canada, a society with a comprehensive, universal, health
      insurance program. METHODS: A population-based cancer registry was used to
      identify the 357,530 cases of invasive cancer diagnosed in the Canadian province
      of Ontario between 1982 and 1991. Information from the 1986 Canadian census was
      linked to the registry and used to describe the SES of the area in which each
      patient resided. Cox regression was used to describe the association between
      median household income and survival while controlling for age, sex, and the
      region in which the patient resided. The Cox model was fitted in a competing risk
      framework to assess the association between income and the probability of
      specific causes of death. RESULTS: Lung cancer and cancers of the head and neck
      region were relatively more common in poor-income communities, and cancers of the
      breast, CNS, and testis were relatively more common in richer communities. A
      strong and statistically significant association between community income and
      survival was observed in cancers of the head and neck region, cervix, uterus,
      breast, prostate, bladder, and esophagus. Smaller, but significant associations
      were seen in cancers of the lung and rectum. No significant association between
      community income and survival was observed in cancers of the stomach, colon,
      pancreas, or ovary. Analysis of the cause of death showed that community income
      is associated both with the probability of death from cancer and with the
      probability of death from other causes. CONCLUSION: Although Canada's health care
      system was designed to provide equitable access to equivalent standards of care,
      it does not prevent a difference in cancer survival between rich and poor
      communities.

PMID- 9193371
TI  - Methodologic issues in effectiveness research on palliative cancer care: a
      systematic review.
AB  - BACKGROUND: The objective of this report is to explore methodologic issues on the
      basis of a systematic review of the literature of effectiveness research on
      palliative cancer care with regard to selection and characteristics of a study
      population, interventions, and outcome assessment. METHODS: A systematic review
      was performed of randomized clinical trials on comprehensive palliative care with
      quality assessment of the studies by three independent observers, using
      predefined quality criteria. RESULTS: In the literature search, 11 relevant
      studies were identified. Without exception, methodologic problems were
      experienced. In two studies, the problems were so severe that no results were
      reported. Problems were associated with the recruitment of a study population in
      10 studies, its homogeneity in six, patient attrition in four, defining and
      maintaining the contrast between the strategies in six, and selection of the
      outcome variables in four. CONCLUSION: Effectiveness research in palliative care
      is complex and has many pitfalls. To enhance the quality of future palliative
      care trials and the validity of their results, we particularly stress the
      importance of careful case finding, strict eligibility criteria, precise
      documentation of the process of care, and comprehensive outcome measurement. The
      relation of structure, process, and outcome variables in comprehensive palliative
      care should be further explored. It is a challenge for future research to link
      patient outcomes to the quality of care, independent from the autonomous course
      of the disease and from personal characteristics.

PMID- 9193370
TI  - Randomized, double-blind comparison of ondansetron versus ondansetron plus
      metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in
      patients with cancer.
AB  - PURPOSE: To investigate the antiemetic effect and tolerability of the 5
      hydroxytryptamine3(5-HT3) antagonist ondansetron plus the dopamine D2 antagonist
      metopimazine versus ondansetron alone in patients receiving platinum-based
      chemotherapy. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive
      patients who were scheduled to receive two consecutive courses of platinum-based
      chemotherapy were randomized between ondansetron 8 mg intravenously (IV) followed
      by 8 mg orally twice a day plus metopimazine 35 mg/m2 as a 24-hour continuous
      infusion followed by 30 mg orally four times a day for 4 days, or ondansetron
      plus placebo. The study used a double-blind, crossover, placebo-controlled
      design. RESULTS: Ninety-four patients completed the crossover. Complete response
      (CR; no emetic episodes) was obtained on day 1 in 77.7% of the patients who
      received the combination versus 50.0% of those who received ondansetron alone (P
      = .00002), and in 51.7% versus 31.0% on days 2 to 6 (P = .0009). The overall CR
      (days 1 to 6) was 48.9% versus 25.3% (P = .0002). Additionally, significantly
      less nausea was observed with the combination on day 1 (P = .0002), days 2 to 6
      (P = .0001), and days 1 to 6 (P = .00004). Patient preference was 63.6% for the
      combination and 13.6% for ondansetron alone; 22.7% expressed no treatment
      preference (P < .0001; therapeutic gain 50.0%; 95% confidence interval [CI],
      31.6% to 68.4%). Adverse reactions were mild and without significant differences
      between the two treatments. CONCLUSION: Metopimazine plus ondansetron was
      significantly superior to ondansetron alone, concerning all efficacy parameters
      assessed, in patients who received platinum-based chemotherapy.

PMID- 9193372
TI  - Angiosarcoma.

PMID- 9193373
TI  - Treatment of acute myelogenous leukemia.

PMID- 9193374
TI  - Time for education in palliative care.

PMID- 9193375
TI  - Anti-oxidant therapy for ischaemic heart disease: where do we stand?

PMID- 9193376
TI  - Do Japanese statistics on gastric carcinoma need to be revised?

PMID- 9193377
TI  - Diastolic ventricular interaction: Starling (and Bernheim) revisited.

PMID- 9193378
TI  - Carmustine and the lungs .

PMID- 9193379
TI  - Care for dying patients.

PMID- 9193380
TI  - Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence
      of major coronary events in men with previous myocardial infarction.
AB  - BACKGROUND: Epidemiological data suggest that the intake of antioxidants such as
      alpha-tocopherol (vitamin E) and beta-carotene has an inverse correlation with
      the incidence of coronary heart disease. The results from clinical trials of
      antioxidant supplementation in people with known coronary heart disease are
      inconclusive. METHODS: We studied the frequency of major coronary events in 1862
      men enrolled in the alpha-tocopherol beta-carotene Cancer Prevention Study
      (smokers aged between 50 and 69 years) who had a previous myocardial infarction.
      In this randomised, double-blind. placebo-controlled study, men had received
      dietary supplements of alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day),
      both, or placebo. The median follow-up was 5.3 years. The endpoint of this
      substudy was the first major coronary event after randomisation. Analyses were by
      intention to treat. FINDINGS: 424 major coronary events (non-fatal myocardial
      infarction and fatal coronary heart disease) occurred during follow-up. There
      were no significant differences in the number of major coronary events between
      any supplementation group and the placebo group (alpha-tocopherol 94/466; beta
      carotene 113/461; alpha-tocopherol and beta-carotene 123/497; placebo 94/438 [log
      rank test, p = 0.25]). There were significantly more deaths from fatal coronary
      heart disease in the beta-carotene (74/461, multivariate-adjusted relative risk
      1.75 [95% CI 1.16-2.64], p = 0.007) and combined alpha-tocopherol and beta
      carotene groups (67/497, relative risk 1.58 [1.05-2.40], p = 0.03) than in the
      placebo group (39/438), but there was no significant increase in the alpha
      tocopherol supplementation group (54/466, relative risk 1.33 [0.86-2.05], p =
      0.20). INTERPRETATION: The proportion of major coronary events in men with a
      previous myocardial infarction who smoke was not decreased with either alpha
      tocopherol or beta-carotene supplements. In fact, the risk of fatal coronary
      heart disease increased in the groups that received either beta-carotene or the
      combination of alpha-tocopherol and beta-carotene; there was a non-significant
      trend of increased deaths in the alpha-tocopherol group. We do not recommend the
      use of alpha-tocopherol or beta-carotene supplements in this group of patients.

PMID- 9193381
TI  - Diastolic ventricular interaction in chronic heart failure.
AB  - BACKGROUND: Diastolic ventricular interaction describes a situation in which the
      volume of one ventricle is directly influenced by the volume of the other
      ventricle. Such interaction is normally negligible, but it is accentuated in
      circumstances associated with pulmonary hypertension and volume overload. When
      this interaction occurs, acute volume unloading results in a reduction in right
      ventricular end-diastolic volume, as expected, but left ventricular end-diastolic
      volume paradoxically increases. Since chronic heart failure is a volume
      overloaded state associated with pulmonary hypertension, we hypothesised that
      this interaction may be clinically important in patients with heart failure.
      METHODS: A radionuclide technique incorporating cardiac scintigraphy was used to
      measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body
      suction, on right and left ventricular end-diastolic volumes in 21 patients with
      chronic heart failure and 12 healthy individuals (controls). FINDINGS: In nine
      heart-failure patients, there was a paradoxical increase in left ventricular end
      diastolic volume in association with an expected decrease in right ventricular
      end-diastolic volume during lower-body suction. This response was not seen in the
      control group. The mean change in left ventricular end-diastolic volume differed
      significantly between the heart-failure patients and controls (6 [SD 19] vs -19
      [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic
      volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients
      who increased left ventricular end-diastolic volume during lower-body suction had
      higher resting pulmonary arterial and pulmonary capillary wedge pressures than
      the remaining heart-failure patients. INTERPRETATION: The response of nine
      patients in our study suggests diastolic ventricular interaction, which we
      believe could be common in patients with chronic heart failure. This finding is
      relevant to their management, since it emphasises the importance of venodilator
      therapy. The relation between stroke volume and left ventricular end-diastolic
      volume, by the Frank-Starting law of the heart, may explain why some patients
      with chronic heart failure paradoxically increase stroke volume when pulmonary
      capillary wedge pressure is lowered with vasodilators.

PMID- 9193383
TI  - Hypofrontality in schizophrenia: distributed dysfunctional circuits in
      neuroleptic-naive patients.
AB  - BACKGROUND: There have been reports that patients with schizophrenia have
      decreased metabolic activity in prefrontal cortex. However, findings have been
      confounded by medication effects, chronic illness, and difficulties of
      measurement. We aimed to address these problems by examination of cerebral blood
      flow with positron emission tomography (PET). METHODS: We studied 17 neuroleptic
      naive patients at the early stages of illness by means of image analysis and
      statistical methods that can detect abnormalities at the gyral level. FINDINGS:
      An initial omnibus test with a randomisation analysis indicated that patients
      differed from normal controls at the 0.06 level. In the follow-up analysis, three
      separate prefrontal regions had decreased perfusion (lateral, orbital, medial),
      as well as regions in inferior temporal and parietal cortex that are known to be
      anatomically connected. Regions with increased perfusion were also identified
      (eg, thalamus, cerebellum, retrosplenial cingulate), which suggests an imbalance
      in distributed cortical and subcortical circuits. INTERPRETATION: These
      distributed dysfunctional circuits may form the neural basis of schizophrenia
      through cognitive impairment of the brain, which prevents it from processing
      input efficiently and producing output effectively, thereby leading to symptoms
      such as hallucinations, delusions, and loss of volition.

PMID- 9193382
TI  - Differences in diagnostic criteria for gastric carcinoma between Japanese and
      western pathologists.
AB  - BACKGROUND: There have been many studies on gastric carcinoma in populations with
      contrasting cancer risks. We aimed to find out whether the criteria for the
      histological diagnosis of early gastric carcinoma were comparable in Western
      countries and Japan. METHODS: Eight pathologists from Japan, North America, and
      Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and
      18 endoscopic mucosal resections taken from 17 Japanese patients with lesions
      ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The
      pathologists were given a list of pathological criteria and a form on which they
      were asked to indicate the criteria on which they based each diagnosis. FINDINGS:
      For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia,
      whereas the Japanese diagnosed definite carcinoma in four slides, suspected
      carcinoma in one, and adenoma in only two. Of 12 slides with high-grade
      adenoma/dysplasia according to most Western pathologists the Japanese gave the
      diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing
      high-grade adenoma/dysplasia with suspected carcinoma according to most Western
      pathologists the Japanese diagnosed definite carcinoma in all. There were no
      major differences in the diagnoses of three slides showing reactive epithelium
      and seven slides with clearly invasive carcinoma. When the opinion of the
      majority of the pathologists was taken as the final diagnosis there was agreement
      between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95%
      CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion
      for most Western pathologists whereas for the Japanese nuclear features and
      glandular structures were more important. INTERPRETATION: In Japan, gastric
      carcinoma is diagnosed on nuclear and structural criteria even when invasion is
      absent according to the Western viewpoint. This diagnostic practice results in
      almost no discrepancy between the diagnosis of a superficial biopsy sample and
      that of the final resection specimen. This may also contribute to the relatively
      high incidence and good prognosis of gastric carcinoma in Japan when compared
      with Western countries.

PMID- 9193384
TI  - Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion
      of cerebral cortex in never-treated schizophrenics.
AB  - BACKGROUND: Studies of schizophrenia by single photon emission computed
      tomography (SPECT) and positron emission tomography (PET) have shown both
      regional cerebral hyperperfusion and hypoperfusion. The aim of this study was to
      examine the inter-relations between regional cerebral blood flow (rCBF),
      psychopathology, and effects of neuroleptic therapy. METHODS: 24 never-treated
      patients with acute schizophrenia were examined with hexamethylpropyleneamine
      oxime brain SPECT and assessed psychopathologically according to the positive and
      negative syndrome scale; they were studied again after neuroleptic treatment and
      psychopathological remission. rCBF values that deviated from those of 20 controls
      by more than 2 SD were regarded as abnormal. FINDINGS: Both hyperperfused and
      hypoperfused patterns were found among schizophrenia patients during acute
      illness. The seven positive symptoms on the symptom scale showed different
      correlations with rCBF: formal thought disorders and grandiosity correlated
      positively (and strongly) with bifrontal and bitemporal rCBF; delusions,
      hallucinations, and distrust correlated negatively (and strongly) with cingulate,
      left thalamic, left frontal, and left temporal rCBF. Stereotyped ideas as a
      negative symptom correlated negatively (and strongly) with left frontal,
      cingulate, left temporal, and left parietal rCBF. After neuroleptic treatment
      (and reduction of positive symptoms), only negative symptoms correlated
      exclusively with bifrontal, bitemporal, cingulate, basal ganglia, and thalamic
      hypoperfusion. INTERPRETATION: Different positive symptoms are accompanied by
      different rCBF values--some related to hyperperfusion, others to hypoperfusion.
      This finding may help to explain observed inconsistencies of perfusion patterns
      in drug-naive schizophrenics.

PMID- 9193385
TI  - Turning a blind eye.

PMID- 9193386
TI  - Magnetic resonance imaging of the brain of premature infants.

PMID- 9193387
TI  - Intravenous nitrate vasodilators and exhaled nitric oxide.

PMID- 9193388
TI  - Widespread occurrence of integrons causing multiple antibiotic resistance in
      bacteria.

PMID- 9193389
TI  - Increased left-ventricular mass after losartan treatment.

PMID- 9193390
TI  - Autism and macrocephaly.

PMID- 9193391
TI  - Pancreatorenal syndrome associated with combination antiretroviral therapy in HIV
      infection.

PMID- 9193392
TI  - Treatment of chronic tennis elbow with botulinum toxin.

PMID- 9193393
TI  - Coeliac disease.

PMID- 9193394
TI  - Disease in Egyptian mummies: the contribution of new technologies.

PMID- 9193395
TI  - Rethinking anaemia surveillance.

PMID- 9193396
TI  - Amiodarone after myocardial infarction: EMIAT and CAMIAT trials.

PMID- 9193397
TI  - Amiodarone after myocardial infarction: EMIAT and CAMIAT trials.

PMID- 9193398
TI  - Amiodarone after myocardial infarction: EMIAT and CAMIAT trials.

PMID- 9193399
TI  - Amiodarone after myocardial infarction: EMIAT and CAMIAT trials.

PMID- 9193400
TI  - Amiodarone after myocardial infarction: EMIAT and CAMIAT trials.

PMID- 9193401
TI  - Is it refractory idiopathic thrombocytopenic purpura?

PMID- 9193402
TI  - Association of insulin gene VNTR polymorphism with polycystic ovary syndrome.

PMID- 9193403
TI  - Endometrial resection versus hysterectomy in management of menorrhagia.

PMID- 9193404
TI  - Live oral cholera vaccine.

PMID- 9193406
TI  - Valsalva vitreous haemorrhage and retinopathy in sickle cell haemoglobin C
      disease.

PMID- 9193405
TI  - Abnormal colonic position as an explanation for radiculopathy.

PMID- 9193407
TI  - Diagnosis of appendicitis.

PMID- 9193408
TI  - Refugee relief rations.

PMID- 9193409
TI  - Attitudes to xenotransplantation.

PMID- 9193410
TI  - The illness of Gerard Manley Hopkins.

PMID- 9193411
TI  - Expert witnesses under scrutiny.

PMID- 9193413
TI  - Eurosurgery 97. Athens, Greece, 3-7 June 1997. Abstracts.

PMID- 9193412
TI  - Wound licking and nitric oxide.

PMID- 9193414
TI  - Introduction of an ultrasound picture archiving and communication system:
      experience in the first year.
AB  - OBJECTIVE: To describe the authors' first year's experience with a picture
      archiving and communication system (PACS) for the management and storage of
      ultrasound images and to discuss the financial impact of the system in terms of
      costs of purchase, installation and operation. MATERIALS AND METHODS: The Toronto
      Hospital, General Division, performs more than 30000 ultrasound studies each
      year. On June 27, 1994, an Ultra PACS (ALI Technology Incorporated, Richmond, BC)
      was introduced as the only method of image storage and archiving in the
      Ultrasound Division. RESULTS: After structural renovations and a detailed work
      flow analysis, the Ultrasound Division converted from film to the PACS over a
      single weekend with no back-up. The advantages to date include consistently high
      quality images; rapid image retrieval (images from the same day [online], 0 to 45
      seconds; archived images [online], 3 to 5 minutes; images in storage [offline], 3
      minutes); no loss of images; more efficient patient through-put, which allows the
      division to handle the same number of patients in 20% less operational time
      (change from a 10-hour day to an 8-hour day, over a 5-day week); less end-of-day
      overtime; and an improved work environment. There has been no change in the
      division's complement of full-time equivalent technologists, the number of film
      librarians has been reduced by 1, and physician service time has decreased by
      20%. There has been no significant impact on overall operational financial
      status. CONCLUSION: The PACS has proved an efficient method for managing large
      numbers of ultrasound images in a cost-effective and technically sound manner.
      Its installation provides the basis for meeting the Ultrasound Division's next
      objective, to eliminate paper as the primary method of managing patient
      information and reports.

PMID- 9193416
TI  - The diagnostic challenge of vasculitis in a patient presenting with acute
      cholecystitis and a focal pancreatic mass: case report.

PMID- 9193415
TI  - Liver transplantation: review of the literature. Part 1: Anatomic features and
      current concepts.
AB  - The first attempted human orthotopic liver transplantation, in 1963, involved a
      child with biliary atresia, who died on the operating table as a result of
      uncontrollable coagulopathy. Improvements in immunosuppression, surgical
      technique, medical imaging and postoperative care, as well as more stringent
      patient selection, have allowed the development of liver transplantation and its
      universal acceptance as the treatment for a variety of liver diseases. The
      radiologist plays a major role in the multidisciplinary transplantation team and
      must be familiar with each stage of orthotopic liver transplantation and its
      associated complications. In the first article of this series, the author reviews
      the anatomic features and current concepts relevant to orthotopic liver
      transplantation. Future articles will discuss the vascular, biliary and medical
      complications of the operation.

PMID- 9193417
TI  - Computed tomographic diagnosis of small-bowel volvulus: case report.

PMID- 9193418
TI  - Correlation between thermosensor temperature and transrectal ultrasonography
      during prostate cryoablation.
AB  - OBJECTIVE: To determine if the adequacy of freezing in the neurovascular bundle
      region of the prostate during prostate cryotherapy can be monitored by
      transrectal ultrasonography (TRUS). PATIENTS AND METHODS: The study group
      consisted of 11 patients undergoing TRUS-guided prostate cryotherapy. The actual
      temperature in the gland was monitored with thermosensors placed in each
      prostatic neurovascular bundle. The 2 cryo-operators, working together and
      blinded to the actual temperature, used sonographic observations to estimate the
      temperature at the neurovascular bundles every 2 minutes until they believed that
      the gland was adequately frozen. The congruity between the estimated and measured
      temperatures was analyzed to determine if the operators could accurately monitor
      the progress of cryoablation by ultrasonography. RESULTS: There were a total of
      85 data points for which the operators thought tumoricidal cryo-injury had been
      achieved at the neurovascular bundles (temperature -20 degrees C or below). For
      these points the measured temperature was on average 6.0 degrees C warmer than
      the estimated temperature (standard deviation, 22). For operator estimates of -20
      degrees C or below, the measured temperature was -20 degrees C or below for 37
      (44%) data points, between -19 degrees C and 0 degree C for 32 (38%) and greater
      than 0 degree C for 16 (19%). CONCLUSIONS: The operators were not able to
      accurately predict subzero temperatures at the neurovascular bundle region by
      TRUS evaluation. Moreover, the bias and magnitude of the error were significant
      and might lead to inadequate freezing of the prostate during attempted
      cryoablation.

PMID- 9193419
TI  - Renal angiomyolipomas: long-term follow-up of embolization for acute hemorrhage.
AB  - OBJECTIVE: To determine if elective, angiographically directed embolization of
      enlarged renal angiomyolipomas can be used to prevent future hemorrhagic episodes
      in patients with tuberous sclerosis and thus avoid nephrectomy. PATIENTS AND
      METHODS: Records were reviewed for all 5 patients who underwent elective,
      subtotal embolization of large, symptomatic angiomyolipomas at the authors'
      institution between 1975 and 1996. RESULTS: All 5 patients had tuberous sclerosis
      and bilateral renal angiomyolipomas. Initial embolization in these patients was
      performed in 1975, 1981, 1993 (2 patients) and 1994. In 1 patient only a single
      embolization session was required. In another, initial embolization on the left
      side was followed by embolization on the right 13 months later. Two patients
      underwent 2 sessions, and 1 patient had 4 sessions over a 13-year period.
      Subtotal embolization with particulate material led to a decrease in size of the
      most severely affected portion of the kidney. One large angiomyolipoma underwent
      sterile liquefaction after embolization; percutaneous catheter drainage was
      required. The embolization allowed subsequent partial nephrectomy in this
      patient. CONCLUSION: Embolization is effective for the long-term management of
      renal angiomyolipomas in patients with tuberous sclerosis; in this way
      nephrectomy and loss of renal function can usually be avoided.

PMID- 9193420
TI  - Etidronate therapy decreases the sensitivity of bone scanning with methylene
      diphosphonate labelled with technetium-99m.
AB  - OBJECTIVE: To define the nature, incidence and consequence of a possible
      interaction between etidronate (for the treatment of hypercalcemia) and methylene
      diphosphonate labelled with technetium-99m (99mTc-MDP) (for bone scanning).
      MATERIALS AND METHODS: The authors reviewed hospital pharmacy records for a
      period of 2 years and identified 18 patients who had received etidronate. Of this
      group, 6 patients (4 men and 2 women, ranging in age from 56 to 76 years) had
      undergone bone scanning with 99mTc-MDP while receiving etidronate. Five of the
      patients had hypercalcemia associated with metastatic disease, and the sixth had
      hyperparathyroidism. RESULTS: All bone scans demonstrated poor uptake of tracer
      by bone accompanied by high soft-tissue background. There was loss of bone
      definition below the mid-thigh, and in 5 of the 6 patients there was
      indistinguishable rib uptake. In 1 of the patients, there was absence of uptake
      in 2 previously defined metastatic lesions. CONCLUSION: Recent oral or
      intravenous administration of etidronate is a contraindication to bone
      scintigraphy, as it markedly decreases sensitivity for bone disease. Bone
      scintigraphy should be timed so that it is performed before etidronate treatment
      or, if that is not possible, more than 2 to 4 weeks after the therapy has been
      completed.

PMID- 9193421
TI  - Residents' corner. Answer to case of the month #48. Intramural hematoma of the
      esophagus after sclerotherapy of esophageal varices.

PMID- 9193422
TI  - Residents' corner. Answer to case of the month #49. Right paraduodenal hernia.

PMID- 9193423
TI  - Predicting outcomes in severe heart failure.

PMID- 9193424
TI  - Repolarization and the genesis of cardiac arrhythmias. Role of body surface
      mapping.

PMID- 9193425
TI  - Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome
      2q31-q32.
AB  - BACKGROUND: The pathogenesis of primary pulmonary hypertension (PPH) is unknown,
      although in some instances families with multiple affected members suggest a
      genetic etiology. METHODS AND RESULTS: We used microsatellite markers and linkage
      analysis in a large family with PPH to determine the chromosomal location of
      their disease gene. We tested a second, ethnically distinct, family for
      cosegregation of disease with markers from the linked region. We mapped the
      disease locus PPH1; GDB/HUGO designation (GDB:1381541; July 1996), approved when
      this work was accepted for publication in abstract form (Circulation.
      1996;94[suppl I]:1-49.), in these families to a 27-cM region on chromosome 2q31
      q32, with a maximum lod score of 3.87 associated with markers D2S350 and D2S364.
      CONCLUSIONS: Cosegregation of this region with disease in different ethnic groups
      suggests that we mapped an important locus in familial PPH. Careful study of
      additional families and sporadic cases will be required to confirm this
      localization of PPH1 and characterize its overall role.

PMID- 9193426
TI  - Plasma angiotensin-converting enzyme activity and left ventricular dilation after
      myocardial infarction.
AB  - BACKGROUND: Left ventricular dilation after acute myocardial infarction (MI) is
      mainly determined by infarct size. In addition, this detrimental structural
      adaptation seems to be augmented in patients with the ACE DD genotype. The ACE DD
      genotype is associated with increased ACE activity. The aim of the present study
      was to evaluate whether ACE activity per se may carry prognostic significance for
      subsequent left ventricular dilation as assessed by echocardiography during 1
      year follow-up after acute MI. METHODS AND RESULTS: Left ventricular end-systolic
      and end-diastolic volume indexes were assessed by two-dimensional
      echocardiography. In 102 consecutive patients, plasma ACE activity was determined
      3.7 +/- 0.1 hours after the onset of MI. In 64 of these patients, left
      ventricular volume indexes obtained at baseline and 1 year after MI were used for
      the present analysis. Patients were divided ino a group having low ACE activity
      (< or = IU/L, n = 15) and a group having high ACE activity (> 12 IU/L, n = 49).
      Infarct size was a significant predictor of the increase in left ventricular
      volume indexes (P = .0001) in these patients. Multivariate regression analysis,
      after correction for infarct size, demonstrated that elevated plasma ACE activity
      is a significant predictor of the increase in left ventricular end-diastolic and
      end-systolic volume indexes (P = .0006 and P = .02, respectively) 1 year after
      MI. CONCLUSIONS: Elevated plasma ACE activity determined soon after the onset of
      MI may be a significant predictor of the development of left ventricular dilation
      and may identify patients at risk.

PMID- 9193427
TI  - Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment
      with dobutamine.
AB  - BACKGROUND: Global left ventricular dysfunction after successful resuscitation is
      well documented and appears to be a major contributing factor in limiting long
      term survival after initial recovery from out-of-hospital sudden cardiac death.
      Treatment of such postresuscitation myocardial dysfunction has not been examined
      previously. METHODS AND RESULTS: Systolic and diastolic parameters of left
      ventricular function were measured in 27 swine before and after successful
      resuscitation from prolonged ventricular fibrillation cardiac arrest. Dobutamine
      infusions (10 micrograms.kg-1.min-1 in 14 animals or 5 micrograms.kg-1.min-1 in 5
      animals) begun 15 minutes after resuscitation were compared with controls
      receiving no treatment (8 animals). The marked deterioration in systolic and
      diastolic left ventricular function seen in the control group after resuscitation
      was ameliorated in the dobutamine-treated animals. Left ventricular ejection
      fraction fell from a prearrest 58 +/- 3% to 25 +/- 3% at 5 hours after
      resuscitation in the control group but remained unchanged in the dobutamine (10
      micrograms.kg-1.min-1) group (52 +/- 1% prearrest and 55 +/- 3% at 5 hours after
      resuscitation). Measurement of the constant of isovolumic relaxation of the left
      ventricle (tau) demonstrated a similar benefit of the dobutamine infusion for
      overcoming postresuscitation diastolic dysfunction. The tau rose in the controls
      from 28 +/- 1 milliseconds (ms) prearrest to 41 +/- 3 ms at 5 hours after
      resuscitation whereas it remained constant in the dobutamine-treated animals (31
      +/- 1 ms prearrest and 31 +/- 5 ms at 5 hours after resuscitation). CONCLUSIONS:
      Dobutamine begun within 15 minutes of successful resuscitation can successfully
      overcome the global systolic and diastolic left ventricular dysfunction resulting
      from prolonged cardiac arrest and cardiopulmonary resuscitation.

PMID- 9193428
TI  - Cytomegalovirus infection-enhanced cardiac allograft vasculopathy is abolished by
      DHPG prophylaxis in the rat.
AB  - BACKGROUND: A wealth of clinical and experimental evidence exists for
      cytomegalovirus (CMV) infection as an accelerating factor in the development of
      cardiac allograft vasculopathy. In this study, the impact of 9-(1,3-dihydroxy-2
      propoxymethyl) guanine (DHPG) on rat CMV infection-enhanced cardiac allograft
      vasculopathy is investigated. METHODS AND RESULTS: Heterotopic rat cardiac
      allografts were performed from the DA to the WF rat strain, and the recipients
      were immunosuppressed with cyclosporine A 2 mg.kg-1.d-1 s.c. for a period of 90
      days until the end of experiment. Two groups of recipients were infected
      intraperitoneally with 10(5) plaque-forming units of rat CMV, whereas one group
      was left noninfected and used as controls. One group of rat CMV-infected rats was
      treated with DHPG with an initial dose of 20 mg/kg i.p. and a maintenance dose of
      10 mg/kg i.p. twice a day from 1 day before transplantation to 30 days after
      transplantation. Compared with noninfected rats, rat CMV infection was associated
      with a significant increase in intimal thickening, from 0.68 +/- 0.10 to 1.30 +/-
      0.12 score units (P < .01), and double the number of vessels affected (P < .01).
      DHPG treatment significantly reduced intimal thickening in rat CMV-infected rats,
      from 1.30 +/- 0.12 to 0.68 +/- 0.13 score units (P < .01), and halved the number
      of vessels affected (P < .01). CONCLUSIONS: The present results demonstrate that
      DHPG prophylaxis entirely abolishes the accelerating effect of rat CMV infection
      on cardiac allograft vasculopathy in immunosuppressed rat recipients, which is
      consistent with our earlier findings demonstrating a similar effect in
      nonimmunosuppressed rat aortic allografts. Taken together, these results suggest
      that DHPG might be useful in the prevention of CMV-accelerated cardiac allograft
      vasculopathy among heart transplant recipients.

PMID- 9193429
TI  - Vitamin C improves endothelium-dependent vasodilation in forearm resistance
      vessels of humans with hypercholesterolemia.
AB  - BACKGROUND: Endothelium-dependent vasodilation is impaired in humans with
      hypercholesterolemia. Oxidative degradation of endothelium-derived nitric oxide
      plays a major role in endothelial dysfunction in animal models of
      hypercholesterolemia. To assess whether this mechanism is relevant to humans, we
      studied the effect of vitamin C, an antioxidant, on vasodilator function in
      forearm resistance vessels of patients with hypercholesterolemia. METHODS AND
      RESULTS: We studied 11 hypercholesterolemic and 12 healthy control subjects.
      Forearm blood flow was determined by venous occlusion plethysmography.
      Endothelium-dependent vasodilation was assessed by intra-arterial infusion of
      methacholine (0.3 to 10 micrograms/min). Endothelium-independent vasodilation was
      measured by intra-arterial infusion of nitroprusside (0.3 to 10 micrograms/min)
      and verapamil (10 to 300 micrograms/min). Forearm blood flow dose-response curves
      were determined for each drug before and during coadministration of vitamin C (24
      mg/min). In hypercholesterolemic subjects, endothelium-dependent vasodilation to
      methacholine was augmented by coinfusion of vitamin C (P = .001); in contrast,
      endothelium-independent vasodilation to nitroprusside and verapamil were not
      affected by coinfusion of vitamin C (P = .8 and P = .3, respectively). In control
      subjects, vitamin C administration did not alter endothelium-dependent
      vasodilation (P = .2). CONCLUSIONS: We conclude that vitamin C improves
      endothelium-dependent vasodilation in the forearm resistance vessels of patients
      with hypercholesterolemia. These findings suggest that nitric oxide degradation
      by oxygen-derived free radicals contributes to abnormal vascular reactivity in
      hypercholesterolemic humans.

PMID- 9193430
TI  - Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam
      Study.
AB  - BACKGROUND: Impaired fibrinolytic capacity, as assessed by euglobulin clot lysis
      time or plasma concentration of fibrinolytic parameters, has been associated with
      an increased risk of myocardial infarction (MI). We studied the association of a
      polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and
      activity) with the prevalence of MI. METHODS AND RESULTS: A case-control study
      was performed. Subjects with a history of MI (n = 121) and controls (n = 250)
      were drawn from the Rotterdam Study, a population-based cohort study of 7983
      subjects > or = 55 years old. We determined TPA antigen and activity in plasma
      and genotyped all subjects for the Alu repeat insertion/deletion polymorphism in
      intron h in the TPA gene. Homozygosity for the insertion was associated with
      twice as many cases of MI as was homozygosity for the deletion (odds ratio, 2.24;
      95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI;
      compared with that in the lowest quartile, the relative risks (odds ratio) in the
      second, third, and upper quartiles were 1.7 (CI, 0.9-3.3), 2.3 (1.2-4.4), and 2.0
      (1.0-3.8), respectively. When adjusted for body mass index, HDL and total
      cholesterol, systolic and diastolic blood pressures, and current smoking, the
      risk associated with TPA antigen concentration was attenuated. Increased
      concentrations of TPA activity tended to be associated with an increased risk of
      MI. CONCLUSIONS: This study provides evidence for an independent association of
      the insertion allele of the insertion/deletion polymorphism in the TPA gene with
      nonfatal MI. Increased TPA antigen is associated with an increased risk of MI;
      however, this association was not independent of cardiovascular disease risk
      factors.

PMID- 9193431
TI  - Genetic variant showing a positive interaction with beta-blocking agents with a
      beneficial influence on lipoprotein lipase activity, HDL cholesterol, and
      triglyceride levels in coronary artery disease patients. The Ser447-stop
      substitution in the lipoprotein lipase gene. REGRESS Study Group.
AB  - BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis
      of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a
      candidate gene in atherogenesis. We previously demonstrated that two amino acid
      substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with
      elevated triglycerides and lower HDL cholesterol and are present with greater
      frequency in coronary artery disease (CAD) patients than in normolipidemic
      control subjects. Conversely, a third frequent mutation in this gene, the Ser447
      Stop, is reported by some investigators to underlie higher HDL cholesterol levels
      and would represent a beneficial genetic variant in lipoprotein metabolism. We
      therefore sought conclusive evidence for these allegations by investigating the
      effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity,
      HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820)
      with normal to mildly elevated total and LDL cholesterol levels. METHODS AND
      RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had
      significantly higher postheparin LPL activity (P = .034), normal postheparin HL
      activity (P = .453), higher HDL cholesterol levels (P = .013), and lower
      triglyceride levels (P = .044) than noncarriers. The influence of the Ser447-Stop
      allele on LPL activity was pronounced in patients using beta-blockers (P = .042)
      and not significant in those not using them (P = .881), suggesting a gene
      environment interaction between the Ser447-Stop mutation and beta-blockers.
      CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant
      positive effect on LPL activity and HDL cholesterol and triglyceride levels and
      that certain subgroups of CAD patients carrying the Ser447-Stop mutation will
      have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447
      Stop mutation therefore should have a protective effect against the development
      of atherosclerosis and subsequent CAD.

PMID- 9193432
TI  - Development of cardiovascular risk factors from ages 8 to 18 in Project
      HeartBeat! Study design and patterns of change in plasma total cholesterol
      concentration.
AB  - BACKGROUND: Project HeartBeat! is a longitudinal study of the development of
      cardiovascular risk factors as growth processes. Patterns of serial change, or
      trajectories, from ages 8 to 18 years for plasma total cholesterol concentration
      (TC) and percent body fat illustrate the design and synthetic cohort approach of
      the study. METHODS AND RESULTS: Six hundred seventy-eight children (49.1% female,
      20.1% black) entered the study at ages 8, 11, and 14 years and were followed up
      with examinations every 4 months for < or = 4 years. Multilevel analysis
      demonstrated trajectories for population mean values of TC and percent body fat
      in sex-specific synthetic cohorts from ages 8 to 18 years. Polyphasic patterns of
      change in TC were confirmed, with notable sex differences in age patterns and
      with minimum mean values of TC of 3.85 mmol/L for females and 3.59 for males. As
      illustrated by data for males, the approximate 75th percentile values of mean TC
      ranged from 4.78 mmol/L at its early peak to 4.06 at its late-teen nadir. Percent
      body fat exhibited a trajectory closely parallel with that for TC only for males
      and appeared to be unrelated for females. CONCLUSIONS: The polyphasic trajectory
      for TC from ages 8 to 18 years differs between females and males, indicates
      marked age variation in 75th percentile values and, in males only, closely
      parallels the trajectory for percent body fat. These and other results indicate
      the value of both follow-up every 4 months across age intervals to detect rapid
      risk factor change and the synthetic cohort approach for gaining new insights
      into the dynamics and possible determinants of this change from ages 8 to 18
      years.

PMID- 9193433
TI  - Early versus delayed angiotensin-converting enzyme inhibition therapy in acute
      myocardial infarction. The healing and early afterload reducing therapy trial.
AB  - BACKGROUND: Although ACE inhibitor therapy has been shown to reduce mortality in
      patients with acute myocardial infarction (MI), the optimal dose and the timing
      of its initiation have not been determined. METHODS AND RESULTS: In a double
      blind trial of 352 patients with anterior MI, we compared the safety and
      effectiveness of early (day 1) versus delayed (day 14) initiation of the ACE
      inhibitor ramipril (10 mg) on echocardiographic measures of left ventricular (LV)
      area and ejection fraction (EF). An early, low-dose ramipril (0.625 mg) arm was
      also evaluated. Clinical events did not differ. During the first 14 days, the
      risk of manifesting a systolic arterial pressure of < or = 90 mm Hg was increased
      in both ramipril groups. LVEF increased in all groups during this period, but the
      early, full-dose ramipril group had the greatest improvement in EF (increase:
      full, 4.9 +/- 10.0; low, 3.9 +/- 8.2%; delayed, 2.4 +/- 8.8%; P for trend < .05)
      and was the only group that did not demonstrate a significant increase in LV
      diastolic area. CONCLUSIONS: The results of the present study demonstrated that
      in patients with anterior MI, the early use of ramipril (titrated to 10 mg)
      attenuated LV remodeling and was associated with a prompter recovery of LVEF. The
      use of low-dose regimen did not prevent hypotension and had only intermediate
      benefits on LV size and function. The more favorable effects on LV topography of
      the early use of full-dose ramipril support the results of the major clinical
      trials, which have demonstrated an early survival benefit of ACE inhibition.

PMID- 9193434
TI  - Coronary vasoconstriction during myocardial ischemia induced by rises in
      metabolic demand in patients with coronary artery disease.
AB  - BACKGROUND: In patients with coronary artery disease, a maximal vasodilation of
      the coronary microcirculation is generally assumed to occur during myocardial
      ischemia induced by rises in metabolic demand. However, vasoconstriction has been
      documented during severe prolonged ischemia in animals. The aim of this study was
      to investigate coronary vasomotor tone during pacing-induced ischemia in humans.
      METHODS AND RESULTS: The study included 11 patients with exercise-induced
      ischemia and single-vessel disease of the left anterior descending artery and 7
      control subjects with normal coronary arteries. Blood flow velocity was monitored
      with a Doppler catheter in the left anterior descending artery. Coronary
      resistance index was calculated as the ratio between mean arterial pressure and
      flow velocity. Measurements were obtained at baseline, after intracoronary
      adenosine (2 mg), and during maximal atrial pacing in the absence and presence of
      adenosine. After adenosine administration at rest, coronary resistance decreased
      more in control subjects than in patients (25 +/- 7% of baseline versus 61 +/-
      19%; P < .01). Coronary resistance decreased in all control subjects (P < .01)
      both at maximal pacing (60 +/- 17% of baseline) and after administration of
      adenosine during tachycardia (31 +/- 13% of baseline). By contrast, all 10
      ischemic patients displayed increased coronary resistance at maximal heart rate
      (221 +/- 131% of baseline; P < .01 versus baseline, P < .01 versus control
      subjects). At this stage, adenosine decreased coronary resistance to 44 +/- 20%
      of values observed before injection. Additionally, it reduced ST-segment
      depression in 5 of 8 patients. CONCLUSIONS: In patients with coronary artery
      disease, transient myocardial ischemia induced by increased metabolic demand is
      not associated with maximal vasodilation. Rather, an inappropriate severe
      microvascular vasoconstriction is present that can be abolished by intracoronary
      adenosine.

PMID- 9193435
TI  - Development and prospective validation of a clinical index to predict survival in
      ambulatory patients referred for cardiac transplant evaluation.
AB  - BACKGROUND: Risk stratification of patients with end-stage congestive heart
      failure is a critical component of the transplant candidate selection process.
      Accurate identification of individuals most likely to survive without a
      transplant would facilitate more efficient use of scarce donor organs. METHODS
      AND RESULTS: Multivariable proportional hazards survival models were developed
      with the use of data on 80 clinical characteristics from 268 ambulatory patients
      with advanced heart failure (derivation sample). Invasive and noninvasive models
      (with and without catheterization-derived data) were constructed. A prognostic
      score was determined for each patient from each model. Stratum-specific
      likelihood ratios were used to develop three prognostic-score risk groups. The
      models were prospectively validated on 199 similar patients (validation sample)
      by calculation of the area under the receiver operating characteristic curve for
      1-year event-free survival, the censored c-index for event-free survival, and
      comparison of event-free survival curves for prognostic-score risk strata.
      Outcome events were defined as urgent transplant or death without transplant. The
      noninvasive model performed well in both samples, and increased performance was
      not attained by the addition of catheterization-derived variables. Prognostic
      score risk groups derived from the noninvasive model in the derivation sample
      effectively stratified the risk of an outcome event in both samples (1-year event
      free survival for derivation and validation samples, respectively: low risk, 93%
      and 88%; medium risk, 72% and 60%; high risk, 43% and 35%). CONCLUSIONS:
      Selection of candidates for cardiac transplantation may be improved by use of
      this noninvasive risk-stratification model.

PMID- 9193436
TI  - Body-surface QRST integral mapping. Arrhythmogenic righ ventricular dysplasia
      versus idiopathic right ventricular tachycardia.
AB  - BACKGROUND: Ventricular tachycardia originating in the right ventricle may arise
      in the presence or absence of structural heart disease. The two main causes of
      right ventricular tachycardia are arrhythmogenic right ventricular dysplasia
      (ARVD) and idiopathic right ventricular tachycardia (IRVT) originating from the
      outflow tract. This study was carried out to determine whether body-surface QRST
      integral mapping can differentiate patients with ARVD from patients with IRVT.
      METHODS AND RESULTS: Body-surface QRST integral maps were obtained during sinus
      rhythm in 8 patients with ARVD, 8 patients with IRVT, and 27 healthy control
      subjects. QRST integral maps were analyzed both visually and mathematically. All
      control subjects had a normal dipolar QRST integral map. In all patients with
      ARVD, a specific dipolar QRST integral map with an abnormally large negative area
      covering the entire inferior and right anterior thorax was recorded. In 6 of 8
      patients with IRVT, a normal map pattern was found, whereas the remaining 2
      patients showed an abnormally large negative area on the right anterior thorax.
      CONCLUSIONS: Patients with ARVD display a specific abnormal QRST integral map
      that may be related to delayed repolarization in the structurally abnormal right
      ventricle. The majority of patients with IRVT demonstrate a normal QRST integral
      map. A slightly abnormal QRST integral map was noted in 2 of 8 patients with
      IRVT, which may be related to minor structural abnormalities, undetectable by the
      present routine diagnostic techniques. These preliminary results indicate that
      body-surface QRST integral mapping may become an important diagnostic tool to
      differentiate patients with ARVD from those with IRVT.

PMID- 9193437
TI  - Load-induced growth responses in isolated adult rat hearts. Role of the AT1
      receptor.
AB  - BACKGROUND: Stimulation of the angiotensin II type 1 (AT1) receptor by
      angiotensin II appears to be mandatory for the acute load-induced hypertrophic
      response of cultured neonatal rat cardiocytes, but its role in the adult heart is
      controversial. We tested the hypothesis that AT1 receptor blockade will inhibit
      the acute induction of proto-oncogenes and protein synthesis by the elevation of
      systolic wall stress in isolated beating adult rat hearts. METHODS AND RESULTS:
      Using the established isovolumic perfused heart preparation under constant
      coronary flow, we found that an increment in left ventricular balloon volume
      generated an increase in systolic wall stress. The induction of left ventricular
      c-fos and c-myc mRNA (Northern blotting) was assessed in hearts subjected to
      increased systolic load without AT1 blockade (No AT1, n = 11) and with AT1
      blockade (AT1, n = 11, losartan 40 mg.kg-1.d-1 x 5 days followed by 10(-5) mol/L
      infusion during perfusion). Flaccid hearts (no left ventricular balloon) served
      as controls (C, n = 9). The stimulation of new protein synthesis in response to
      increased systolic load was measured by incorporation of [3H]phenylalanine into
      cardiac proteins. Elevation of systolic load was associated with a twofold (P <
      .05) increase in c-fos and c-myc mRNA levels that was not blocked by losartan.
      The rate of [3H]phenylalanine incorporation into cardiac proteins was increased
      2.7-fold (P < .01) in hearts subjected to increased systolic load compared with
      control hearts. However, AT1 receptor blockade with losartan did not prevent the
      stimulation of [3H]phenylalanine incorporation (881 +/- 97 versus 923 +/- 82
      nmol.g protein-1.h-1, P = NS). CONCLUSIONS: In contrast with immature myocytes
      subjected to stretch, the acute growth responses induced by systolic pressure
      overload in adult rat hearts do not depend on AT1 receptor activation.

PMID- 9193439
TI  - Treatment of sudden cardiac death. Current understandings from randomized trials
      and future research directions.

PMID- 9193440
TI  - Images in cardiovascular medicine. Cor triatriatum in an infant.

PMID- 9193438
TI  - Remodeling of autologous saphenous vein grafts. The role of perivascular
      myofibroblasts.
AB  - BACKGROUND: Aortocoronary saphenous vein grafts (SVGs) undergo structural changes
      that render them susceptible to atherosclerosis. Accordingly, the origin of
      neointimal hyperplasia-was examined in porcine arterialized SVGs to determine the
      mechanism of vein graft remodeling. METHODS AND RESULTS: At 2 to 4 days after
      surgery, the percentage of cells lacking differentiation markers characteristic
      for smooth muscle (SM) cells (ie, alpha-SM actin, desmin, and SM myosin)
      increased within the media of SVGs interposed in the carotid arteries (P < .001).
      At 7 to 14 days, these cells acquired a differentiated phenotype (ie, alpha-SM
      actin positive/ variable desmin/SM-myosin negative) and accumulated in the
      neointima. At 3 months, the neointima was positive for alpha-SM actin but mostly
      negative for desmin, which contrasted with medial SMCs that were invariably
      positive for alpha-SM actin, desmin, and SM myosin. To determine the role of
      nonmuscle cells in the above process, perivascular wound fibroblasts were
      selectively labeled and found to translocate through the media of newly placed
      SVGs, contributing to neointimal formation. These migrating cells differentiated
      to myofibroblasts exhibiting sustained alpha-SM-actin expression. The intima of
      human SVGs, retrieved during repeat aortocoronary bypass surgery, exhibited the
      profile of cytoskeletal proteins that resembled myofibroblasts seen in porcine
      SVGs. CONCLUSIONS: Perivascular fibroblasts may infiltrate injured media of
      arterialized SVGs, differentiate to myofibroblasts (acquiring alpha-SM actin),
      and contribute to vein graft remodeling. The similarities between porcine and
      human SVGs regarding the repertoire of cytoskeletal proteins suggest the
      involvement of myofibroblasts in graft remodeling in the clinical setting.

PMID- 9193441
TI  - Fiber, lipids, and coronary heart disease. A statement for healthcare
      professionals from the Nutrition Committee, American Heart Association.

PMID- 9193442
TI  - Introduction to the symposium Science Education and Dentistry: Improving the
      Connection.

PMID- 9193443
TI  - Science and the shifting paradigm in dental education.
AB  - Dental education is faced with continuing challenges to adjust to external as
      well as internal pressures. These pressures are coming from a variety of sources
      that are often inconsistent in the nature and direction of change they would
      bring about. Pressure on the future direction of dental education are coming from
      sources such as an Institute of Medicine report, Pew Health Professions
      Commission reports, changes in the academic health centers in response to health
      care reform, and expectations of parent universities. Reactions to these and
      other forces are bringing about changes in the nature and extent of scientific
      research in schools of dentistry. As the educational programs continue to evolve,
      research will receive greater attention, and more of it will be funded from
      private sources.

PMID- 9193445
TI  - Problem-based learning at the University of Southern California School of
      Dentistry.
AB  - Responding to the recent Institute of Medicine report on dental education, the
      Center for Craniofacial Molecular Biology (CCMB) of the University of Southern
      California School of Dentistry has developed a parallel track program in dental
      education leading to the D.D.S. degree. This program was proposed in May of 1995,
      and the first class of twelve students was admitted in September of that year.
      Currently two classes are enrolled and plans to admit a further twelve students
      (Class of 2001) are in place. The educational strategy for this program is
      totally problem-based. Students work in groups of six with a faculty facilitator,
      not necessarily a content expert. Facilitators are largely drawn from the
      multidisciplinary pool of research faculty at the center. All learning is
      mediated through biomedical and biodental problem cases. No formal lectures or
      classes are scheduled. The learning of clinical dental skills is promoted through
      focussed dental patient simulations in which students review clinical charts,
      radiographs, medical reports and then explore identified, hands-on learning needs
      using patient simulators in a clinical context. Early patient exposure is
      obtained through dental office visits and other special patient clinics. Initial
      experience with this program suggests that the problem-based learning (PBL)
      students learn as well (if not better) than their traditional program peers and
      develop excellent group and cognitive analytical skills. The absence of a pool of
      dentally related biomedical cases suitable for a PBL program has necessitated the
      use of innovative approaches to their development and presentation. It is
      believed that this educational approach will produce dental clinicians equipped
      with the self-motivated, life-long learning skills required in the ever-changing
      world of bio-dental sciences in the twenty-first century.

PMID- 9193444
TI  - Diversity and critical forces in dental education.
AB  - Critical issues that affect dental education and the connection between science
      and practice include the community, managed patient care, public skepticism and
      fiscal support, and shifting demography in patterns of oral disease as well as
      the background of students entering the dental profession. During the past
      several decades, there have been major shifts in the patterns of oral disease,
      most recently described in results of the NHANES III dental survey. The diversity
      and background of students entering the dental profession have changed
      dramatically as well, and present estimates of change in U.S. population are no
      less volatile. Funding for dental education in constant dollars is decreasing
      nationally, with declining support from state and federal sources and a much
      greater reliance on clinical and development income. Recent recommendations by
      the Institute of Medicine and Pew Health Commission and reactions to those
      recommendations by representative dental organizations-particularly the American
      Dental Association, American Association of Dental Schools, and the American
      Association of Dental Examiners-have significant implications for the structure
      of dental education. All of these factors are tempered by the emergence of
      managed patient care and the implications of that environment to increasing the
      level of academic excellence of students, improving the quality of care delivered
      to patients, and enhancing the scholarly contributions of faculty. These forces
      may represent an opportunity to maintain a well-documented national excellence in
      oral health care, expand the educational options to meet student demand and
      interest, increase the biological and behavioral background of our graduates, and
      explore new educational approaches to preclinical and clinical training.

PMID- 9193446
TI  - What should biomedical sciences education in dental schools achieve?
AB  - Education for the first professional degree in dentistry is intended to produce
      graduates capable of offering a wide range of high quality dental services to the
      general public. More than that, it is expected that graduates will be firmly
      grounded in the scientific basis for their professional practices and be equipped
      to evaluate critically and integrate selectively new scientific findings that
      emerge during their professional lifetimes. In addition, they are expected to be
      able to work effectively with diverse patient populations and to conduct their
      practices with a high level of sensitivity to the ethical and psychosocial
      dimensions of patient care. Indiana University School of Dentistry has undergone
      a process of curriculum reform that has yielded a new first professional degree
      program. Its hallmarks are large, multidisciplinary courses (seven courses in the
      first two years) that are taught using a variety of strategies including problem
      based learning in small groups as well as lectures. The biomedical sciences
      curriculum is concept-based. Students will demonstrate their understanding of
      science concepts and methods by applying them to the solution of research and
      health care problems. Biomedical sciences will be taught at a level that will
      provide a comprehensive understanding of the functioning of the human body in
      health and disease, allow students to assimilate the coming revolution in
      molecular medicine, and selectively use new diagnostics, preventives, and
      therapeutics that evolve as molecular biological technologies yield solutions to
      current medical and dental problems. Using the biomedical sciences curriculum as
      a vehicle, we will also achieve the goal of training dentists as critical
      thinkers, problem solvers, lifelong learners, and ethical practitioners, skillful
      in peer and self-evaluation, and cognizant of the psychosocial as well as
      biomedical perspective of health and disease.

PMID- 9193447
TI  - Making science clinically relevant.
AB  - Clinical practice requires a sound foundation in the basic and clinical sciences.
      However, the traditional dental curriculum often separates the two in a variety
      of ways that reduce their integration. The basic sciences are commonly taught in
      the first two years by a basic science faculty with inconsistent integration with
      clinical dental practice. The clinical sciences are often taught by faculty who
      may not be actively involved in research-related activities. The curriculum is
      dense and is difficult to modify to adapt to evolving scientific discovery and
      application. The 1995 IOM report focuses much of its attention on these issues.
      The Harvard School of Dental Medicine has dramatically modified its curriculum
      twice in the recent past to more closely integrate the basic and clinical
      sciences and to promote the clinical relevance of the basic sciences. The class
      entering in 1980 began a five-year D.M.D. program that was designed to decompress
      the curriculum and increase experiences that enhance scientific and clinical
      integration. The class entering in 1994 initiated a four-year program that uses a
      problem-based learning design throughout the entire curriculum. Strategies for
      integrating the clinical and the basic sciences along with research training and
      experience were developed and implemented in both programs.

PMID- 9193448
TI  - Assessment of dental students' diagnostic accuracy for oral cancer screening.

PMID- 9193449
TI  - Admissions test predictors of performance in a foreign-trained dentist program.

PMID- 9193450
TI  - The aquaporin family of water channel proteins in clinical medicine.
AB  - The aquaporins are a family of membrane channel proteins that serve as selective
      pores through which water crosses the plasma membranes of many human tissues and
      cell types. The sites where aquaporins are expressed implicate these proteins in
      renal water reabsorption, cerebrospinal fluid secretion and reabsorption,
      generation of pulmonary secretions, aqueous humor secretion and reabsorption,
      lacrimation, and multiple other physiologic processes. Determination of the
      aquaporin gene sequences and their chromosomal locations has provided insight
      into the structure and pathophysiologic roles of these proteins, and primary and
      secondary involvement of aquaporins is becoming apparent in diverse clinical
      disorders. Aquaporin-1 (AQP1) is expressed in multiple tissues including red
      blood cells, and the Colton blood group antigens represent a polymorphism on the
      AQP1 protein. AQP2 is restricted to renal collecting ducts and has been linked to
      congenital nephrogenic diabetes insipidus in humans and to lithium-induced
      nephrogenic diabetes insipidus and fluid retention from congestive heart failure
      in rat models. Congenital cataracts result from mutations in the mouse gene
      encoding the lens homolog Aqp0 (Mip). The present understanding of aquaporin
      physiology is still incomplete; identification of additional members of the
      aquaporin family will affect future studies of multiple disorders of water
      distribution throughout the body. In some tissues, the aquaporins may participate
      in the transepithelial movement of fluid without being rate limiting, so
      aquaporins may be involved in clinical disorders without being causative. As
      outlined in this review, our challenge is to identify disease states in which
      aquaporins are involved, to define the aquaporins' roles mechanistically, and to
      search for ways to exploit this information therapeutically.

PMID- 9193451
TI  - Paget bone disease involving young adults in 3 generations of a Korean family.
AB  - Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence
      implicates a "slow virus" infection of the skeleton, perhaps in genetically
      predisposed individuals. PBD is rare in Asia. We describe a Korean family with
      PBD. The propositus noticed bowed limbs at approximately 25 years of age.
      Radiologic studies made when he was 55 years old revealed essentially panostotic
      PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were
      markedly elevated. An iliac crest specimen showed classic histopathologic changes
      of PBD. Additionally, palpable swellings were first observed at age 45 years at
      his occiput, pubic ramus, ileum, and facial bones. They contained numerous
      multinucleated cells and were originally diagnosed as giant cell tumors. However,
      we found that, like osteoclasts, these cells expressed considerable tartrate
      resistant acid phosphatase activity. These "extraskeletal osteoclastomas"
      resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of
      age, were discovered by study of his 5 children to have elevated serum ALP
      activity and OC levels and widespread PBD. Both women, however, are without
      palpable masses and are asymptomatic. The propositus' father, who died at age 55
      years, had similar skeletal deformities beginning at age 20 years, but was not
      examined. Leukocytopenia was found in the 3 living family members with PBD. There
      was no evidence for linkage of the PBD to HLA loci. The condition appears to be
      transmitted as an autosomal dominant trait and is manifest in young adult life.
      Multicentric extraskeletal osteoclastomas with remarkable sensitivity to
      dexamethasone treatment appear to be another unusual feature of this family's
      disorder. In this family, the stimulus for PBD is so great that the PBD is
      apparent at an early age, affects essentially the entire skeleton, and leads to
      the formation or extension of osteoclast-like cells into nonosseous tissues
      (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is
      rare, shows a strong clustering of PBD compatible with autosomal dominant
      inheritance. Leukocytopenia appears to distinguish affected family members, but
      any role for this abnormality in the pathogenesis of PBD is unclear. Our findings
      support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.

PMID- 9193452
TI  - Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple
      Disease. Societe Nationale Francaise de Medecine Interne.
AB  - Whipple disease is a rare, multiorgan disease with prominent intestinal
      manifestations. We report a retrospective clinical study of 52 patients recruited
      in various parts of France from 1967 to 1994. Seventy-three percent of the
      patients were male. Clinical manifestations preceding the diagnosis were
      articular for 35 patients (67%), digestive for 8 patients (15%), general for 7
      patients (14%), and neurologic for 2 patients (4%). At a later stage of the
      disease, 44 patients (85%) presented diarrhea, weight loss, and malabsorption,
      while 8 patients (15%) did not show any gastrointestinal symptom throughout the
      development of the disease. Forty-three patients (83%) presented arthralgia or
      arthritis, and 11 (21%) had prominent neurologic symptoms. In addition,
      cardiovascular symptoms were present in 9 patients (17%); mucocutaneous symptoms,
      in 9 patients (17%); pleuropulmonary symptoms, in 7 patients (13%); and
      ophthalmologic symptoms, in 5 patients (10%). All patients but 1 were given a
      positive diagnosis on histopathologic criteria: jejunal biopsy for 46 patients
      (90%), lymph node biopsy for 3 patients (6%), brain biopsy for 1 patient (2%),
      postmortem jejunal and cerebral biopsy for 1 patient (2%). With treatment, the
      disease evolved favorably in 47 patients (90%), while 5 patients (10%) had
      unfavorable outcomes (2 deaths from neurologic involvement, 1 patient with
      chronic dementia, and 2 patients with digestive symptoms insensitive to
      antimicrobial therapy). Of the 41 patients initially treated successfully and
      whose treatment has been completed, clinical evolution after discontinuation of
      treatment was favorable in 34 cases (83%). Clinical relapses occurred in 7
      patients. No relapse was observed after treatment by trimethoprim
      sulfamethoxazole, alone or following a combination of penicillin and
      streptomycin, or after the combination of penicillin and streptomycin, whatever
      the oral follow-up treatment prescribed. The evolution of patients showing a
      relapse was favorable in all cases after reintroduction of antibiotic therapy.
      These results are discussed in the light of previously published series and case
      reports of Whipple disease. The diagnosis of the disease remains difficult at an
      early phase or when digestive symptoms are absent. It is noteworthy that proximal
      enteroscopy is sometimes misleading, considered normal on macroscopic examination
      and nonspecific on pathologic grounds. A normal erythrocyte sedimentation rate
      represents another pitfall. Histopathology is the key for positive and
      differential diagnosis, and may require multiple and repeated biopsies. Findings
      from molecular biology confirm the central role of an uncultured Gram-positive
      bacillus which was named in 1992 Tropheryma whippelii. A recent report suggests
      that polymerase chain reaction (PCR) analysis of peripheral blood might allow the
      diagnosis of Whipple disease in some cases. However, immunologic or cellular
      parameters such as macrophagic function may play an important, although not
      clearly elucidated, role in the pathogeny of the disease. Trimethoprim
      sulfamethoxazole should be considered the antimicrobial agent of choice in the
      treatment of Whipple disease, minimizing the risk of cerebral involvement and
      relapses.

PMID- 9193453
TI  - Enhanced hepatotoxicity of acetaminophen in the alcoholic patient. Two case
      reports and a review of the literature.
AB  - We report 2 fatal cases of the acetaminophen-alcohol syndrome and review 51
      reported cases in the medical literature. The MEDLINE database from January 1966
      to December 1995 and bibliographies of selected articles were used to obtain the
      case reports. Inclusion criteria were a clear history of alcohol use, a history
      of acetaminophen use and/or an elevated serum acetaminophen level, peak aspartate
      aminotransferase (AST) greater than 800 U/L, and exclusion of other causes of
      hepatotoxicity by negative hepatitis serologies and/or a liver biopsy showing
      typical findings of acetaminophen toxicity. Demographic characteristics, clinical
      features, treatment, and outcome were extracted from reports meeting inclusion
      criteria and our own 2 cases. This syndrome affected relatively young, frequently
      healthy patients. Acetaminophen was invariably taken for nonsuicidal intent. The
      mortality rate was 32%. A typical laboratory picture was defined, characterized
      by an extraordinarily high AST level. Treatment with N-acetylcysteine was not
      effective due to delayed presentation and diagnosis. Patients who use alcohol and
      health care providers should be educated about this potentially fatal syndrome.
      Prevention is the key to reducing its occurrence.

PMID- 9193454
TI  - Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical
      presentation, histology, survival, and outcome.
AB  - Diffuse alveolar hemorrhage (DAH) complicating systemic lupus erythematosus (SLE)
      remains a devastating pulmonary complication of this systemic disease. We
      conducted this study to review the clinicopathologic presentation and the effects
      of prior treatment, presence of infection, and current treatment on the survival
      and outcome of patients with DAH and SLE. We reviewed the records of 15 SLE
      patients who experienced 19 episodes of DAH over a 10-year period in a single
      tertiary care hospital. These patients were compared with 57 previously reported
      cases. The 19 episodes of DAH represented 3.7% of the 510 admissions occasioned
      by various complications of SLE. As previously reported, the majority (66%) were
      women with a median age of 27 years. The onset was often abrupt: < 3 days in 12
      of the episodes. In 3 patients (20%), DAH was the initial manifestation of SLE,
      compared with 11% in the literature series. In the other patients in the present
      series, DAH appeared a median of 31 months following the diagnosis of SLE, versus
      35 months in the literature series. In only 42% of the episodes in the present
      series, compared with 66% in the literature series, was hemoptysis present at the
      time of admission. However, hemoptysis eventually appeared in all 19 episodes.
      Temperature elevation (> 38 degrees C) was another inconsistent finding, found in
      only 5 episodes (26%) in the present series. The most constant concurrent
      systemic finding was lupus nephritis (14/15 patients). This represents a
      significant increase when compared with the literature series (29/48 patients).
      In 8 of 10 patients in whom lung tissue was available, pulmonary capillaritis
      accompanied the DAH. This represents a marked difference in the underlying
      histologic pattern when compared with the literature series. In those patients,
      72% (31/43 patients) had bland pulmonary hemorrhage, and capillaritis was
      described in only 6 patients. The overall patient mortality rate was 53% in the
      current series and 50% in the literature series. Factors associated with an
      increased mortality in the present series include the following: mechanical
      ventilation (62%) versus no mechanical ventilation (0%); infection (78%) versus
      no infection (20%); and cyclophosphamide therapy for the acute DAH episode (70%)
      versus no cyclophosphamide therapy (20%). The incidence of infection in DAH and
      SLE (9/19 episodes) is far greater than previously reported (7/ 57 episodes). One
      possible explanation for this difference is the increased use of outpatient
      immunosuppressive therapy with monthly intravenous cyclophosphamide therapy for
      lupus nephritis. Eighteen DAH episodes in the present series were treated with
      intravenous methylprednisolone. When one combines both the current and literature
      series experience (16 episodes), the use of plasmapheresis does not improve
      survival. Of the 7 patients in the present series who survived all episodes of
      DAH, 6 remain alive a median of 50 months post episode and without recurrence of
      DAH. Diffuse alveolar hemorrhage is an uncommon but lethal complication of SLE.
      The survival rate remains unchanged from previous reports. The absence of
      hemoptysis should not exclude this diagnosis, particularly in those patients who
      experience an acute pulmonary syndrome with new radiographic infiltrates
      accompanied by falling hematocrit and the presence of a hemorrhagic
      bronchoalveolar lavage. Evidence for lupus nephritis is present in the great
      majority of cases. Most cases demonstrate the histologic pattern of pulmonary
      capillaritis. The mortality is adversely affected by the need for mechanical
      ventilation, either the presence of infection at the time of admission or the
      development of infection in the hospital, and the use of cyclophosphamide for
      treatment of the acute event.

PMID- 9193455
TI  - Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic
      characteristics of 50 patients from our clinics and the recent literature.
AB  - We analyzed the clinical, radiologic, and immunologic characteristics of 50
      patients with chorea and the antiphospholipid syndrome (APS) (6 from our clinics
      and 44 from a MEDLINE computer-assisted review of the literature from 1985
      through 1995). Forty-eight (96%) patients were female and 2 (4%) were male.
      Twenty-nine (58%) patients had defined systemic lupus erythematosus (SLE), 6
      (12%) had "lupus-like" syndrome, and 15 (30%) patients had "primary" APS. Mean
      age of patients in this series was 23 +/- 12 years (range, 6-77 yr); mean age at
      presentation of chorea was 21 +/- 12 years (range, 6-77 yr). In 11 (22%)
      patients, the onset of chorea was in childhood (6-14 yr), and in 2 (4%) patients
      it presented at 60 years or more. Six (12%) patients developed chorea soon after
      they started taking estrogen-containing oral contraceptives, 3 (6%) developed
      chorea gravidarum, and 1 (2%) patient developed chorea shortly after delivery.
      Most patients (66%) presented only 1 episode of chorea. Chorea was bilateral in
      55% of patients. Computed tomography and magnetic resonance imaging scans
      reported cerebral infarcts in 35% of patients. The following antibodies were
      detected: lupus anticoagulant (92%), anticardiolipin antibodies (91%),
      antinuclear antibodies (82%), anti-DNA (59%), anti-Ro (10%), anti-RNP (8%), anti
      La (2%), and anti-Sm (2%). The chorea in these patients responded to a variety of
      medications, for example, steroids, haloperidol, antiaggregants, anticoagulants,
      or a combination of therapy, usually prescribed in the presence of other
      manifestations of APS or SLE. However, many patients responded well to
      haloperidol and to the discontinuation of oral contraceptives if this was the
      precipitating factor.

PMID- 9193456
TI  - Clinical relevance of transforming growth factor-beta 1 in the urine of patients
      with hepatocellular carcinoma.
AB  - To assess the clinical relevance of transforming growth factor-beta 1 (TGF-beta
      1) in the urine of patients with hepatocellular carcinoma (HCC), TGF-beta 1 was
      measured, by radioimmunoassay, in 140 patients with HCC, 50 cirrhotic patients,
      30 patients with chronic active hepatitis, and 50 healthy controls. The results
      indicate that there were significantly increased urinary TGF-beta 1 levels in
      patients with HCC. Raised TGF-beta 1 levels were associated, in a dose-related
      fashion, with increased risk for development of HCC (odds ratio, 1.05, 95%
      confidence interval, 1.03-1.07). HCC patients with raised TGF-beta 1 levels had
      shorter survival than those with normal TGF-beta 1 levels (p = 0.038). TGF-beta 1
      levels decreased after successful anticancer therapy (p < 0.0001). There was an
      inverse correlation between TGF-beta 1 and serum alpha-fetoprotein (AFP) (r = 
      0.199, p < 0.04). Receiver operating characteristics (ROC) curve analysis
      indicated that parallel determination of TGF-beta 1 and AFP significantly
      increased the sensitivity and diagnostic accuracy, with a high specificity. In
      conclusion, raised urinary TGF-beta 1 was associated with HCC development. It is
      a predictor of poor prognosis, and a tumor marker for diagnosis and therapeutic
      follow-up of HCC.

PMID- 9193457
TI  - Toward the use of surgical placebo-controlled trials.

PMID- 9193458
TI  - Transplantation of testis-derived Sertoli cells into the mammalian brain.

PMID- 9193459
TI  - New approaches for control of anti-self-reactivity in type 1 diabetes and
      transplantation of pancreatic islets.

PMID- 9193460
TI  - Efficient myoblast transplantation in mice immunosuppressed with monoclonal
      antibodies and CTLA4 Ig.

PMID- 9193461
TI  - Potential role of CD34 stem cells in tolerance induction.

PMID- 9193462
TI  - Improved outcome of pig islet isolation by Pefabloc inhibition of trypsin.

PMID- 9193463
TI  - Crude collagenase loses islet-isolating efficacy regardless of storage
      conditions.

PMID- 9193464
TI  - Isolation of human hepatocytes from livers rejected for whole organ
      transplantation.

PMID- 9193465
TI  - Ex vivo preparation of porcine hepatocytes for use in bioartificial hepatic
      support systems.

PMID- 9193466
TI  - Influence of variables on canine islet isolation results.

PMID- 9193467
TI  - Enrichment of hematopoietic stem cells from human vertebral body marrow.

PMID- 9193468
TI  - Characterization of baboon vertebral body marrow.

PMID- 9193469
TI  - An automated method for flow-cytometric analysis of human vertebral body marrow.

PMID- 9193470
TI  - Effect of extrapancreatic collagenase concentration on canine islet isolation
      outcome.

PMID- 9193471
TI  - Characterization of pediatric vertebral bone marrow.

PMID- 9193474
TI  - Variables affecting human vertebral body marrow yields.

PMID- 9193472
TI  - Development of an automated computer-controlled islet isolation system.

PMID- 9193473
TI  - Human islet isolation using a new enzyme blend.

PMID- 9193475
TI  - Increased immunogenicity of human vertebral body marrow after processing in
      bovine versus human serum albumin.

PMID- 9193476
TI  - Efficacy of a new collagenase for canine and murine islet isolation.

PMID- 9193477
TI  - Phenotypic analysis of a human hematopoietic cell line with lymphoid and myeloid
      features using simultaneous multicolor flow cytometry.

PMID- 9193478
TI  - Islet yield and early function in rat-to-mouse transplantation using different
      types of collagenase.

PMID- 9193479
TI  - Optimizing of isolation, purification and function of islets from the pancreas of
      the adult large German pig.

PMID- 9193480
TI  - Improved baboon pancreatic islet cell isolation.

PMID- 9193481
TI  - Re-evaluation of donor factors affecting islet isolation from human pancreas
      using a two-step digestion method.

PMID- 9193482
TI  - Canine islet isolation using a two-step digestion method and the influence of
      stationary collagenase incubation of the pancreas.

PMID- 9193483
TI  - Assessment of isolated islet equivalents.

PMID- 9193484
TI  - Differentiation of free and embedded porcine pancreatic islets using a novel
      automated image analysis algorithm.

PMID- 9193485
TI  - Beraprost sodium improves islet yield and viability in canine islet
      cryopreservation.

PMID- 9193486
TI  - Serum-free medium and pyruvate improve survival and glucose responsiveness of
      islet beta cells in culture.

PMID- 9193487
TI  - The intracellular ATP content of fresh and cultured human islets isolated from
      different donors.

PMID- 9193488
TI  - In vitro glucose sensitivity of cultured human and porcine islets.

PMID- 9193489
TI  - Culture of human islets before transplantation in serum-free media.

PMID- 9193490
TI  - Successful cryopreservation of rat islets using ethylene glycol.

PMID- 9193492
TI  - Optimization of removal of cryoprotectant from frozen-thawed islets.

PMID- 9193491
TI  - Effects of pefloxacin on rat pancreatic islet cell function after 24-hour cold
      preservation.

PMID- 9193493
TI  - Water and DMSO permeability at 22 degrees C, 5 degrees C, and -3 degrees C for
      human pancreatic islet cells.

PMID- 9193494
TI  - Maintenance of in vitro and in vivo viability of bovine islets during prolonged
      (3 months) culture.

PMID- 9193495
TI  - Cryopreservation of principal islets of teleost fish: the effect on function and
      islet xenograft survival.

PMID- 9193496
TI  - In vitro function of pig islets isolated from bleach-treated pancreata.

PMID- 9193497
TI  - Interaction between human humoral factors and swine bone marrow cells (an
      experimental report).

PMID- 9193498
TI  - Intrasplenic hepatocyte transplantation in the pig: new technical aspects.

PMID- 9193499
TI  - Telomerase activity and phenotypic characterization in harvested bone marrow from
      a child with a germline cell cancer.

PMID- 9193500
TI  - Soluble factor(s) alone produced by primary porcine microvascular endothelial
      cells support the proliferation and differentiation of human CD34+ hematopoietic
      progenitor cells with a high replating potential.

PMID- 9193501
TI  - Ex vivo expansion of primitive murine hematopoietic progenitor cells on porcine
      endothelial cells.

PMID- 9193502
TI  - Requirements for optimal insulin secretion capacity of human fetal islet graft.

PMID- 9193504
TI  - Mechanism of trapping of intravenously transplanted lymphocytes in the liver.

PMID- 9193503
TI  - The kinetics of seeding of syngeneic cells from vascularized bone marrow grafts.

PMID- 9193506
TI  - Long-term culture of galanin expressing encapsulated RIN 1056a cells in vitro.

PMID- 9193505
TI  - Neither nitric oxide nor PGE2 synthesis mediate the effects of cytokines on fetal
      rat islets.

PMID- 9193507
TI  - Insulin secretory studies on isolated pig islets.

PMID- 9193508
TI  - Effect of donor age on porcine insulin secretion.

PMID- 9193509
TI  - Histologic study of beta cells in porcine pancreas aged 5, 12, and 24 weeks.

PMID- 9193510
TI  - Fate of a small number of islets transplanted into diabetic mice.

PMID- 9193511
TI  - Ex vivo replicative potential of adult human peripheral blood CD4+ T cells.

PMID- 9193512
TI  - Effect of hepatocyte growth factor on the proliferation of transplanted
      hepatocytes in the spleen.

PMID- 9193513
TI  - Highly porous polymer matrices as a three-dimensional culture system for
      hepatocytes: initial results.

PMID- 9193514
TI  - Glucose toxicity alters growth hormone-induced potentiation of insulin secretion
      in isolated human fetal islets: a reversible effect.

PMID- 9193515
TI  - Response of human chondrocytes cultured in vitro to human somatotropin,
      triiodothyronine, and thyroxine.

PMID- 9193516
TI  - Culture, expansion, and transplantation of human fetal neural progenitor cells.

PMID- 9193517
TI  - Function of hepatic stimulatory substance-induced proliferating hepatocytes in
      ODS-od/od rats.

PMID- 9193518
TI  - Nicotinamide and sodium butyrate for the induction of fetal porcine beta-cell
      differentiation prior to transplantation.

PMID- 9193520
TI  - Acute stress impairs lymphocyte function but spares pancreatic endocrine
      function.
AB  - In the same animal, following HS and recovery, pancreatic islet function remains
      intact while immunologic functions are impaired. Cellular responses to thermal
      stresses are complex and tissue specific.

PMID- 9193521
TI  - Pancreatic islet microcirculation: a scanning electron microscopic study of
      corrosion casts.

PMID- 9193519
TI  - Monoclonal antibodies to the cell surface of a unique human lymphoid/myeloid cell
      line detect epitopes absent from peripheral blood mononuclear cells.

PMID- 9193522
TI  - The prerenal peritoneum as an alternative site for pancreatic islet
      transplantation.

PMID- 9193524
TI  - ATP content of isolated islets: indication for species-dependent vulnerability
      for cell-mediated graft rejection?

PMID- 9193523
TI  - Transient macrophage inactivation decreases the occurrence of early graft loss in
      rodents.

PMID- 9193525
TI  - In vivo immune response to allogeneic hepatocytes.

PMID- 9193526
TI  - Bovine-to-porcine intrathymic islet xenotransplantation.

PMID- 9193529
TI  - Human mixed lymphocyte-islet cultures: the influence of heterologous proteins on
      islet immunogenicity.

PMID- 9193527
TI  - NK cells, macrophages, and humoral immune responses are dominant in primary
      nonfunction of islet grafts in the dog-to-rat xenotransplant model.

PMID- 9193528
TI  - Endothelial cell dysfunction after intraportal islet cell transplant in rats.

PMID- 9193530
TI  - Acute death after intraportal hepatocyte transplantation in an allogeneic rat
      strain combination: a possible role for complement activation.

PMID- 9193531
TI  - Possible role of preformed natural antibodies in preventing bone marrow
      engraftment in a discordant xenogeneic species combination (human-to-mouse).

PMID- 9193532
TI  - Prevention of primary nonfunction after porcine islet allotransplantation.

PMID- 9193533
TI  - Nonspecific rapid elimination of transplanted allogeneic bone marrow cells.

PMID- 9193536
TI  - Intrathymic cell allografts followed through a major graft challenge.

PMID- 9193535
TI  - Iothalamate and ioversol radiocontrasts do not affect islet survival and
      production of nitric oxide after intrahepatic transplant in rodents.

PMID- 9193534
TI  - Mechanisms of rejection of nonvascularized grafts: the role of perforin and Fas.

PMID- 9193538
TI  - Detection and morphologic evaluation of allotransplanted rat pancreatic islet
      cells.

PMID- 9193537
TI  - Xenotransplantation of fish islets into the non-cryptorchid testis.

PMID- 9193539
TI  - Hepatic regeneration induces normoglycemia in diabetic rats previously
      transplanted into the liver with a subtherapeutic islet mass.

PMID- 9193540
TI  - Laparoscopic cholecystectomy and islet cell transplantation in a type I diabetic
      patient.

PMID- 9193541
TI  - Intravenous glucose tolerance tests after porcine islet auto- and
      allotransplantation.

PMID- 9193542
TI  - Transplanted cardiomyocytes survive in scar tissue and improve heart function.

PMID- 9193543
TI  - Comparison of various sites of islet autotransplantation in the canine model.

PMID- 9193545
TI  - Development of a laparoscopic approach for islet transplantation.

PMID- 9193546
TI  - Islet intraportal transplant through a percutaneous catheter placed in a portal
      vein tributary in pigs.

PMID- 9193544
TI  - Experimental xenotransplantation of fresh isolated and cryopreserved pig
      hepatocytes: a biochemical and morphological study.

PMID- 9193547
TI  - Transplantation of human hepatocytes.

PMID- 9193548
TI  - Major impact of engraftment site on early functional outcome of discordant
      xenoislet grafts from a large animal donor.

PMID- 9193549
TI  - Cerebral spinal fluid shunt is an immunologically privileged site for
      transplantation of xenogeneic islets.

PMID- 9193550
TI  - Immunoprotection provided by the bioartificial pancreas in a xenogeneic host.

PMID- 9193551
TI  - In vitro bioartificial skin culture model of tissue rejection and
      inflammatory/immune mechanisms.
AB  - We hypothesized that an in vitro bioartificial skin rejection model using living
      LSEs grown in tissue culture could be developed for the study of autologous,
      allogenic, and/or xenogeneic inflammatory/immune mechanisms and topical
      immunosuppressive drugs. Human fibroblasts were mixed with type 1 rat-tail
      collagen to form a matrix (4 to 5 days), on which human keratinocytes were
      seeded. After a keratinocyte monolayer formed, CT cultures were raised to the air
      liquid interface for continued growth. In the REJ LSE model, immunocytes isolated
      from human blood were seeded on top of the NHEK monolayer at the time of air
      lifting. Thickness measurements of the acellular keratin and keratinocyte layers,
      and nuclear/cytoplasmic ratios, in both CT and REJ were made using digital image
      analysis. Immunostaining with anticytokeratin demonstrated a viable, keratin
      producing epidermal layer; staining with anti-TGF-beta suggested a role for this
      cytokine in the rejection or wound-healing process. The LSE appeared
      histologically similar to normal human epidermis. Immunocytes added to the REJ
      cultures caused an obvious rejection response and were clearly identifiable in
      the gels as CD45+ staining cells. The LSE model appears promising for the study
      of immune/inflammatory mechanisms, thermal injury, screening antirejection agents
      that might be applied topically and as an in vitro replacement for skin graft
      studies in animals.

PMID- 9193552
TI  - Primary culture of adult rat hepatocytes on porous expanded
      polytetrafluoroethylene.

PMID- 9193553
TI  - In vitro activation of human lymphocytes by crude and purified alginates.

PMID- 9193554
TI  - Effects of alginate/polyaminoacidic coherent microcapsule transplantation in
      adult pigs.

PMID- 9193555
TI  - Microencapsulation of neonatal porcine islets: long-term reversal of diabetes in
      nude mice and in vitro protection from human complement mediated cytolysis.

PMID- 9193557
TI  - Immunoisolation of xenogeneic islets using a living tissue engineered cartilage
      barrier.

PMID- 9193556
TI  - Development of biocompatible barium alginate microcapsules.

PMID- 9193558
TI  - Microdialysis for in vivo evaluation of permeability of immunoisolation devices.

PMID- 9193559
TI  - Combined xenotransplantation of encapsulated hepatocytes and pancreatic islets.

PMID- 9193560
TI  - Insulin secretion of free and AN69 encapsulated islets.

PMID- 9193561
TI  - Islet number in an immunobarrier device required to treat diabetes in mice.

PMID- 9193563
TI  - Assessment of the protective effect of uncoated alginate microspheres.

PMID- 9193562
TI  - Effect of molecular weight exclusion of polysulfone fibers on macroencapsulated
      pig islet xenograft function in diabetic mice.

PMID- 9193564
TI  - Permeability characteristics of microencapsulated pancreatic islets.

PMID- 9193565
TI  - Immunomodulatory activities of the somatostatin receptor subtype analogues on
      human peripheral blood lymphocytes.

PMID- 9193567
TI  - Cytokine transcripts in peripheral blood cells during immunosuppressive induction
      therapy in allogeneic human islet transplantation.

PMID- 9193566
TI  - Aminoguanidine inhibits the generation of nitric oxide in vitro and prolongs
      islet xenograft survival in rats.

PMID- 9193568
TI  - Effect of leflunomide and cyclosporine on concordant xenogeneic islet
      transplantation in streptozotocin-induced and autoimmune diabetic mice.

PMID- 9193569
TI  - 1,25-Dihydroxyvitamin D3 reduces MHC antigen expression on pancreatic beta-cells
      in vitro.

PMID- 9193572
TI  - Anti-CD4/CyA therapy causes prevention of autoimmune but not allogeneic
      destruction of grafted islets in BB rats.

PMID- 9193571
TI  - Effect of mycophenolate mofetil with and without anti-CD4 (GK1.5) on fetal islet
      iso-, allo-, and xenografts in NOD/Lt female mice.

PMID- 9193570
TI  - 15-Deoxyspergualin attenuates pericapsular cellular infiltration and prolongs
      survival of alginate-poly-L-lysine-alginate microencapsulated islets.

PMID- 9193574
TI  - Allotrap prolongs survival of porcine islet xenografts in diabetic mice.

PMID- 9193573
TI  - Successful xenotransplantation of adult porcine islets in NOD and BALB/c mice
      with leflunomide and cyclosporine.

PMID- 9193576
TI  - Documentation in bone-marrow-augmented organ recipients of the presence of
      dendritic cell progenitors of donor origin.

PMID- 9193577
TI  - Liver allograft tolerance: do donor thymus-independent T cells play a role?
      Preliminary results in a nude rat model.

PMID- 9193575
TI  - Functional outcome of discordant xenoislet grafts from a large animal donor after
      recipient defibrinogenation with Ancrod.

PMID- 9193578
TI  - PCR-flow analysis used to detect the levels of chimerism in peripheral blood of
      bone-marrow infused organ allograft recipients at the time of rejection episodes.

PMID- 9193579
TI  - Immune response after syngeneic and allogeneic blood cell transplantation.

PMID- 9193580
TI  - Rat renal allograft tolerance is associated with local TGF-beta and absence of IL
      2r expression within chimeric immunocytic foci.
AB  - Tolerance was induced in Lewis (LEW) rat renal allograft recipients of Brown
      Norway kidneys by multiple pretransplant donor-blood transfusions and prior
      limited cyclosporine A. Rat renal allograft tolerance was associated with the
      induction of systemic donor T cells (10%), an early phase of nonspecific
      suppressor-cell generation, followed by maturation of systemic antigen-specific
      suppressor cells, and renal cellular infiltrates that develop long-term in situ
      in the kidney graft model. It was hypothesized that these infiltrates represent
      chimeric immunocytic foci that are locally regulated via a TGF-beta-dependent
      mechanism. Both immunohistochemical staining and digital image analysis for
      cellular and extracellular TGF-beta, IL-2 receptor (CD25), and the BN Class I-MHC
      marker (OX-27) were performed. Control rejecting (REJ) kidneys did not
      demonstrate any differences with respect to levels of infiltrating immunocyte
      area vs long-term surviving (TOL) kidneys (3.9% vs 4.5%, P = .303).
      Immunostaining with the BN Class I MHC marker (OX-27) demonstrated high levels of
      chimerism within immunocyte foci of the tolerant grafts (OX-27 BN+immunocytes
      49.0% +/- 5.1%). In situ cellular IL-2 receptor (CD25) expression was
      demonstrated in REJ kidney infiltrates but not within TOL immunocytic
      infiltrating foci, when measured as percent of total lymphocytes (REJ = 5.0% vs
      TOL = 0.4%, P = .031). Conversely, TGF-beta expression was significantly higher
      in immunocytes of TOL kidneys when measured as the number of DAB chromogen
      staining pixels per total immunocyte area (TOL = .076 vs REJ = .047, P = .003).
      In conclusion, these results suggested that stable mixed immune chimerism (SMIC)
      plays an important role in DST-CyA-induced tolerance in situ. SMIC-induced
      tolerance may involve a local TGF-beta-dependent mechanism that is associated
      with in situ TGF-beta (+) and IL-2r (-) immunocytes.

PMID- 9193582
TI  - Involvement of Fas and Fas ligand interaction in allogeneic hepatocyte rejection
      in the spleen.

PMID- 9193581
TI  - Humoral mechanism of split tolerance to lymphocyte and heart allografts after
      donor-specific transfusion.

PMID- 9193583
TI  - Infusion of class II DIM donor bone marrow enhances islet allograft survival in
      low-dose CyA treated dogs.

PMID- 9193584
TI  - Bone marrow engraftment and GVHD following bone marrow transplantation across a
      concordant xenogeneic barrier (mouse to rat).

PMID- 9193585
TI  - Perioperative donor bone marrow infusion in recipients of organ allografts.

PMID- 9193587
TI  - Donor-recipient cross has marked impact on islet survival and primary
      nonfunction.

PMID- 9193586
TI  - Role of in situ IL-2r and TGF-beta expression in tolerant vascularized bone
      marrow (limb) transplant chimeras.
AB  - We hypothesized that an increase in IL-2 activated T cells in situ within the
      marrow component of a transplanted limb may adversely affect development of
      tolerance, while increased TGF-beta expression locally would facilitate tolerance
      induction and/or maintenance. Digital image analysis of cellular expression of IL
      2r in the bone marrow was significantly increased in the CON and TXP limbs for
      both GVHD and tolerant recipients as compared to normal limb marrow (P < .02).
      The amount of cellular expression of TGF-beta was significantly increased in the
      GVHD animals, both CON and TXP, as compared to the tolerant animals (43.2 +/- 3.1
      vs 10.6 +/- 2.6; P < .000001). Our results show that increased IL-2r and TGF-beta
      expression in situ within the bone marrow is an important effect common to both
      alloimmune tolerance and GVHD induction with VBMT chimeras. The dramatic increase
      in the expression of TGF-beta in the GVHD transplanted limbs may explain the
      profound immunosuppression that results. Additionally, moderate expression of TGF
      beta in situ in tolerant chimeras may represent a mechanism for the induction and
      maintenance of tolerance.

PMID- 9193588
TI  - Toward the biologic release of human insulin from skeletal muscle.

PMID- 9193589
TI  - Use of biolistic particle accelerator to introduce genes into isolated islets of
      Langerhans.

PMID- 9193590
TI  - A methodology for an efficient and reproducible gene transfer into porcine islets
      using cationic liposomes.

PMID- 9193591
TI  - IL-10 and TGF-beta gene transfer for xenogeneic islet transplantation: comparison
      of effect in concordant vs discordant combination.

PMID- 9193594
TI  - Gene gun-mediated gene transfer and expression in rat islets.

PMID- 9193592
TI  - Transfer of genes for IL-10 and TGF-beta to isolated human pancreatic islets.

PMID- 9193593
TI  - IL-10 and TGF-beta gene transfer to rodent islets: effect on xenogeneic islet
      graft survival in naive and B-cell-deficient mice.

PMID- 9193595
TI  - Adenovirus-mediated gene transfer to the xenogeneic liver in liver
      xenotransplantation: the transduction of complement regulatory factor genes (DAF
      and HRF20).

PMID- 9193596
TI  - Effect of CTLA4-Ig gene transfer using adenoviral vector in organ and cell
      transplantation.

PMID- 9193597
TI  - Adenovirus-mediated gene transfer of antisense ribozyme for alpha
      (1,3)galactosyltransferase gene and alpha (1,2)fucosyltransferase gene in
      xenotransplantation.

PMID- 9193598
TI  - Expression of chloramphenicol acetyl transferase activity in the spleen after
      transplantation of hepatocytes transfected with pSV2CAT plasmid by
      electroporation.

PMID- 9193600
TI  - Analysis of a human fetal pancreatic islet cell line.

PMID- 9193599
TI  - Reversal of hyperglycemia in diabetic NOD mice by human proinsulin gene therapy.

PMID- 9193601
TI  - Gene expression via direct injection of plasmid vector into the thymus.

PMID- 9193602
TI  - Potential of immortalized neural progenitor cells to replace lost adult central
      nervous system neurons.

PMID- 9193604
TI  - More than 5-year islet allograft function in insulin-dependent diabetes mellitus.

PMID- 9193603
TI  - In vitro characterization of hammerhead ribozymes against perforin and fas-ligand
      RNA.

PMID- 9193605
TI  - Long-term (> 30 months) follow-up of a single successful kidney-islet transplant
      recipient.

PMID- 9193608
TI  - Liver-islet transplantation in type 2 diabetes.

PMID- 9193610
TI  - Vertebral body procurement from multiorgan donors for bone marrow harvest.

PMID- 9193607
TI  - An attempt to reverse diabetes by delayed islet cell transplantation in humans.

PMID- 9193609
TI  - Comparison of transplanted islets in patients with functioning versus
      nonfunctioning allografts.

PMID- 9193612
TI  - An Internet multicast symposium concerning the microcirculation of the islets of
      Langerhans.

PMID- 9193611
TI  - Removal of preformed cytotoxic antibody using PROSORBA (Staph Protein-A-Silica)
      column without immunosuppression.

PMID- 9193606
TI  - Human gene therapy with myoblast transfer.

PMID- 9193613
TI  - Human renal allograft rejection in the SCID/rat radiation chimera.

PMID- 9193614
TI  - T-helper 1 and 2 activation with fresh or cultured allo- or xenoislets.

PMID- 9193615
TI  - Donor parameters of pancreas grafts processed for islet or beta-cell isolation
      and transplantation.

PMID- 9193616
TI  - Pig islet xenoantigens recognized by human preformed natural antibodies: a
      preliminary definition.

PMID- 9193617
TI  - Studies of alpha-Gal dependent hyperacute xenotransplant rejection using double
      knockout embryonic stem cells.

PMID- 9193618
TI  - Quantitative assessment of the development of hepatoma in a buffalo rat model.

PMID- 9193619
TI  - Improvement of adult porcine islet recovery by early collagenase injection and
      low temperature digestion.

PMID- 9193620
TI  - Utilization of the Diabetes Research International Network.

PMID- 9193621
TI  - Sensitization to HLA antigens in islet recipients with failing transplants.

PMID- 9193622
TI  - Gene expression of isolated fetal hepatocytes transplanted into rat spleen.

PMID- 9193624
TI  - Analysis of factors influencing immediate renal function after cadaveric renal
      transplantation.

PMID- 9193623
TI  - Automated counting and sizing of isolated porcine islets using digital image
      analysis.

PMID- 9193625
TI  - Possible use of fetal bone as two-step bone grafting material--Part 2:
      Antigenicity of fetal bone and time suitable for fetal bone grafting.

PMID- 9193626
TI  - Prolongation of corneal xenograft survival with deoxyspergualin and anti-LFA-1
      monoclonal antibody.

PMID- 9193627
TI  - Microchimerism in renal transplant recipients correlates with better HLA-DRB1
      matched status.

PMID- 9193628
TI  - Minimally invasive method to measure hepatic protein synthesis rate of the
      pretransplant graft: a use of 21-G Chiba type II skinny needle.

PMID- 9193629
TI  - Role of costimulatory molecules on airway epithelial cells acting as alloantigen
      presenting cells.

PMID- 9193630
TI  - Treatment of murine cardiac allograft by monoclonal antibodies to IL-2 receptor
      alpha chain and beta chain.

PMID- 9193631
TI  - Mono(ADP-ribosyl)transferases and related enzymes in animal tissues. Emerging
      gene families.
AB  - Mono-ADP-ribosylation, like phosphorylation, is an enzyme-catalyzed, reversible
      post-translational modification that modulates protein function. It was
      originally discovered as the pathogenic principle of diphtheria-, cholera-, and
      other potent bacterial toxins. By analogy, corresponding enyzmes were postulated
      to exist in animal tissues, and mounting biochemical evidence indicates that such
      enzymes, indeed, play important regulatory roles in cellular functions. The
      molecular cloning of the first mammalian mono(ADP-ribosyl)transferase from rabbit
      skeletal muscle, the finding of its homology to a well-studied T-cell marker,
      RT6, and the molecular cloning of additional gene family members from mammals and
      birds is providing fresh impetus to research in this field. Intriguingly, these
      vertebrate enzymes are predicted to be secretory or membrane proteins. They are
      expressed in lymphatic tissues, muscle, testis, bone marrow, and erythroblasts.
      Here we review the relationship between this novel family of eucaryotic mono(ADP
      ribosyl)transferases (mADPRTs), ADP-ribosylating bacterial toxins, the poly(ADP
      ribose)polymerase (PARP), the ADP-ribosyl cyclases, and the ADP-ribosylprotein
      hydrolase (ARH) in terms of their structure, enzymatic properties and possible
      biological functions.

PMID- 9193632
TI  - ADP-ribose. A historical overview.
AB  - ADP-ribosylation of proteins was first detected as a modification of nuclear
      proteins by polymeric ADP-ribose residues derived from NAD+. Subsequently, the
      field developed into three destinct sections: (i) Possible function(s) of poly
      ADP-ribosylation with increasing evidence for participation in DNA excision
      repair and perhaps in DNA recombination; (ii) Mono-ADP-ribosylation as a
      mechanism to inactivate (by some toxins) or to regulate enzymes/proteins (e.g. in
      bacterial nitrogen fixation, in protein traffic through membranes, in
      intercellular communication); (iii) Intramolecular ADP-ribosylation converting
      NAD+ to cyclic ADP-ribose, a possible Ca(2+)-mobilizing agonist. Thus, NAD+ first
      known as a cofactor of oxidoreductases has experienced an impressive
      metamorphosis from a housekeeping coenzyme to a multifunctional group transfering
      metabolite involved in an increasing number of intracellular and intercellular
      regulatory loops.

PMID- 9193633
TI  - ADP-ribosylarginine hydrolases and ADP-ribosyltransferases. Partners in ADP
      ribosylation cycles.
AB  - Mono-ADP-ribosylation is a reversible modification of arginine residues in
      proteins, with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine
      hydrolases constituting opposing arms of a putative ADP-ribosylation cycle. The
      enzymatic components of an ADP-ribosylation cycle have been identified in both
      prokaryotic and eukaryotic systems. The regulatory significance of the cycle has
      been best documented in prokaryotes. As shown by Ludden and coworkers, ADP
      ribosylation controls the activity of dinitrogenase reductase in the phototropic
      bacterium Rhodospirillum rubrum. ADP-ribosylation of other amino acids, such as
      cysteine, has also been demonstrated, lending credence to the hypothesis that
      this modification is heterogeneous. In eukaryotes, the functional relationship
      between ADP-ribosyltransferases and ADP-ribosylarginine hydrolases is less well
      documented. The transferase-catalyzed reaction results in sterospecific formation
      of alpha-ADP-ribosylarginine from beta-NAD; ADP-ribosylarginine hydrolases
      specifically cleave the alpha-anomer, leading to release of ADP-ribose and
      regeneration of the free guanidino group of arginine. The two reactions can thus
      be coupled in vitro. Coupling in vivo is dependent on cellular localization. The
      deduced amino acid sequences of ADP-ribosyltransferases from avian and mammalian
      tissues have common consensus sequences involved in catalytic activity but, in
      some instances, enzyme-specific cellular localization signals. The presence of
      amino- and carboxy-terminal signal sequences is consistent with the
      glycosylphosphatidylinositol(GPI)-anchoring to the cell surface. The muscle and
      lymphocyte transferases ADP-ribosylate integrins. Some transferases lack the
      carboxy- terminal signal sequence needed for GPI-anchoring. Most ADP
      ribosylarginine hydrolase activity is cytosolic, although perhaps some is located
      at the cell surface. Deduced amino acid sequences of hydrolases from a number of
      mammalian species are consistent with their cytoplasmic localization. Katada and
      coworkers have determined, however, that auto-ADP-ribosylated RT6, a GPI-linked
      protein, is metabolized by a hydrolase-like activity, consistent with the
      existence of an ADP-ribosylation cycle. ADP-ribosyl RT6 may be internalized,
      thereby coming in contact with the cytosolic hydrolase; alternatively, a novel
      form of the hydrolase may be located at the surface. The mechanism of coupling of
      ADP-ribosyltransferases and hydrolases in eukaryotic ADP-ribosylation cycles has
      yet to be clarified.

PMID- 9193634
TI  - Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide.
AB  - The crystal structure of diphtheria toxin (DT) in complex with nicotinamide
      adenine dinucleotide (NAD) has been determined by x-ray crystallography to 2.3 A
      resolution. NAD binds to a cleft on the surface of the catalytic (C) domain of
      DT, interacting closely with the side chains of Tyr54, Tyr65, His21, Thr23, and
      Glu 48. The carboxylate group of Glu148 of Dt lies approximately 4 A from the
      scissile, N-glycosidic bound of NAD, suggesting a possible catalytic role for
      Glu148 in stabilizing a positively charged oxocarbonium intermediate. Residues 39
      46 of the active-site loop of the C-domain become disordered upon NAD-binding,
      suggesting a potential role for these residues in binding to elongation facor-2
      (EF-2). Structural alignments of the DT-NAD complex with the structures of other
      ADP-ribosylating toxins suggest how NAD may bind to these other enzymes.

PMID- 9193636
TI  - Identification of the catalytic site of clostridial ADP-ribosyltransferases.
AB  - The catalytic sites of clostridial ADP-ribosyltransferases were studied by
      photoaffinity-labelling with [carbonyl-14C]NAD+. In C3-like transferases, which
      are known to modify low molecular mass GTP-binding Rho proteins, Glu-174 was
      identified to be essential for catalysis. In C. perfringens iota toxin, Glu-380
      and Glu-378 may have pivotal roles in the active site of this actin-ADP
      ribosylating toxin.

PMID- 9193637
TI  - A proposed role for protein. Protein complexes in the regulation of the
      reversible ADP-ribosylation of dinitrogenase reductase.

PMID- 9193635
TI  - Selection of diphtheria toxin active-site mutants in yeast. Rediscovery of
      glutamic acid-148 as a key residue.
AB  - Saccharomyces cerevisiae was transformed with expression plasmids carrying the
      DTA gene under control of the GAL1 promoter; colonies that formed under inducing
      conditions were selected; and plasmids from these colonies were screened for
      mutations in DTA that failed to block expression of the protein. Substitutions at
      three sites were identified, all of which are in the active-site cleft; and each
      of the substitutions reduced ADP-ribosyltransferase activity by > 10(5). The
      substitutions include a charge reversal mutation of a catalytically important
      residue (Glu148Lys) and replacements of either of two glycines (Gly22 and Gly52)
      with bulky residues. The fact that multiple mutations were identified in these
      same residues implies that there are relatively few sites at which substitutions
      ablate ADP-ribosyltransferase activity without blocking expression of the full
      length protein. Incorporation of a primary attenuating mutation into the DTA gene
      allowed S. cerevisiae also to be used to select complementary secondary mutations
      which altered activity less drastically. Besides elucidating structure-activity
      relationships, mutations identified by these approaches may be useful in
      designing new vaccines.

PMID- 9193639
TI  - Pertussis toxin. Entry into cells and enzymatic activity.
AB  - In this study we present data supporting the concept of a retrograde transport
      mechanism for pertussis toxin to the Golgi complex. We also describe a novel GTP
      binding 32 kDa cellular target protein, which is ADP-ribosylated upon exposure to
      PT and different from the classical PT substrate, the alpha-subunit of Gi
      proteins.

PMID- 9193638
TI  - ADP-ribosylation and early transcription regulation by bacteriophage T4.
AB  - Bacteriophage T4 codes at least for two ADP-ribosylating activities, the 76 kDa
      Alt and the 24 kDa Mod gene products. The main target for both enzymes is the
      host RNA polymerase. We cloned and sequenced the alt gene and overexpressed the
      corresponding enzyme. The recombinant protein shows ADP-ribosylating activities
      in vitro, as had been described earlier for the native enzyme isolated from phage
      heads. The native as well as the recombinant protein ADP-ribosylate the alpha
      subunit of RNA polymerase, but also subunits beta, beta' and sigma 70 and perform
      an autoribosylation reaction. Taking advantage of the pKWIII test system,
      constructed to measure promoter strengths in vivo, it was found that ADP
      ribosylation of RNA polymerase leads to an increase of transcription from T4
      early promoters up to a factor of two. In an infected host cell this should cause
      an enhanced expression of T4 genes. Depending on whether RNA polymerase was ADP
      ribosylated or not, it initiated transcription at T4 promoters with different
      sequence characteristics: unribosylated RNA polymerase recognizes the early T4
      promoters by an extended -10 region, whereas the ribosylated enzyme selects for
      T4 early promoters with an extended T4-specific and highly conserved -35 region.
      These results may reflect how the virus, step by step imposes its genetic program
      on the host cell, and in part they give a rationale for the extension of the
      consensus sequence observed with these promoters. We also sequenced the genomic
      region of the T4 mod gene and found two open reading frames coding both for
      proteins of approximately 24 kDa. Up to now none of the reading frames could be
      cloned into E. coli in an active form, making it highly probable that the ADP
      ribosylation pattern inflicted by gene product Mod on host RNA polymerase is
      deleterious to these bacteria. Comparisons of the amino acid sequences showed
      significant homologies among the two reading frames. Computer analysis reveals
      that both Mod sequences and also the sequence of the Alt protein exhibit a
      structural concordance with the catalytic domains of other prokaryotic ADP-mono
      ribosyltransferases such as the Pseudomonas aeruginosa exotoxin A, the cholera
      labile enterotoxin, the diphteria toxin, the heat labile enterotoxin A of E.
      coli, and pertussis toxin. We present a detailed model for T4 transcription
      regulation.

PMID- 9193640
TI  - Membrane anchored synthetic peptides as a tool for structure-function analysis of
      pertussis toxin and its target proteins.
AB  - Solid phase fixed peptides are useful tools for the investigation of enzyme
      substrate interactions. We could show that interactions of target sequences, like
      e.g. the acceptor domain of G-proteins for the of mono ADP-ribosylation by
      pertussis toxin and the toxin itself can be studied by this method. Reaction
      specificity is identical to modification of free peptides. The method is
      extremely versatile and has enormous potential if the focus is on the effects of
      substrate modification or substrate length.

PMID- 9193641
TI  - Enhanced degradation of stimulatory G-protein (Gs alpha) by cholera toxin is
      mediated by ADP-ribosylation of Gs alpha protein but not by increased cyclic AMP
      levels.
AB  - Cholera toxin (CT) catalyses ADP-ribosylation of the alpha-subunit of stimulatory
      protein (Gs) leading to stimulation of adenylyl cyclase and elevated
      intracellular cAMP. Persistent treatment (24-48 h) of C6 glioma cells with
      cholera toxin (100 ng/ml) caused marked downregulation of Gs alpha (75-80%) which
      could not be mimicked by dibutyryl cAMP (1 mM) and forskolin (10 microM) over the
      same time periods suggesting that CT-mediated Gs alpha downregulation is
      independent of cAMP production. However, CT increased the expression of Gq/11
      alpha proteins at 24 and 48 h of treatment. The increase in mRNA levels of Gq/11
      alpha proteins preceded the increase in Gq/11 proteins. Such stimulatory effects
      of CT were mimicked by forskolin and dibutyryl-cAMP. These results suggest that
      CT-mediated downregulation of Gs alpha is independent of cAMP but CT upregulates
      the expression of Gq/11 alpha proteins in a cAMP-dependent manner.

PMID- 9193642
TI  - Sequence and structural links between distant ADP-ribosyltransferase families.
AB  - The low resolution structure of the Pseudomonas aeroginosa exotoxin A (ETA)
      presented in 1986 provided the first tantalizing three-dimensional view of an ADP
      ribosyl-transferase (ADPRT) catalytic domain. The major features of this protein
      fold have recurred in the more recently solved crystal structures of the cholera
      toxin-related heat-labile enterotoxin (LT), diphtheria toxin (DT) and pertussis
      toxin (PT). A core set of alpha + beta elements define a minimal, conserved
      scaffold with remarkably plastic sequence requirements-only a single glutamic
      acid residue critical to catalytic activity is invariant. Other interchangeable
      residues in locations important for catalysis and binding are suggested by the
      cocrystal structures of DT with the inhibitor ApUp, ETA with bound AMP and
      nicotinamide, and DT with substrate NAD-in close accord with labeling and
      mutagenic data. Faint sequence resemblances that were earlier noticed among
      prokaryotic ADPRTs have now been securely extended by the structural concordance
      between toxin folds; more recently, eukaryotic ADPRTs have surfaced and their
      sequences can be reliably threaded into the conserved core fold. We will briefly
      summarize efforts in Palo Alto and Hamburg to explore these latter relationships,
      and to mount a rigorous search for new ADPRT families in the growing sequence
      databases.

PMID- 9193643
TI  - Molecular cloning and characterization of the T-cell mono(ADP-ribosyl)transferase
      RT6. Relationships to other mADPRTs and possible functions.

PMID- 9193645
TI  - Molecular cloning and characterization of lymphocyte and muscle ADP
      ribosyltransferases.
AB  - Mono-ADP-ribosylation, catalyzed by ADP-ribosyltransferases, is a
      posttranslational modification of proteins in which the ADP-ribose moiety of NAD
      is transferred to an acceptor protein(arginine). Several of the bacterial toxin
      ADP-ribosyltransferases have been well characterized in their ability to alter
      cellular metabolism. It has been postulated that these bacterial toxins mimic the
      actions of transferases from mammalian cells. We have cloned and characterized
      ADP-ribosyltransferases from rabbit and human skeletal muscle, and mouse
      lymphocytes. The muscle transferases are glycosylphosphatidylinositol (GPI)
      anchored proteins that are conserved among species. Two distinct transferases,
      termed Yac-1 and Yac-2 were cloned from mouse lymphoma (Yac-1) cells. The Yac-1
      transferase, like the muscle enzymes, is a GPI-linked exoenzyme. The Yac-2
      transferase, on the other hand, is membrane-associated but appears not to be GPI
      linked. In contrast to Yac-1, the Yac-2 enzyme had significant NAD glycohydrolase
      activity and may preferentially hydrolyze NAD. The bacterial toxin ADP
      ribosyltransferases contain three noncontiguous regions of sequence similarity,
      which are involved in formation of the catalytic site. Alignment of the deduced
      amino acid sequences of the mammalian transferases and the rodent RT6 enzymes,
      along with results from site-directed mutagenesis of the muscle enzyme, are
      consistent with the notion of a common mechanism of NAD binding and catalysis
      among ADP-ribosyltransferases.

PMID- 9193644
TI  - Molecular cloning and characterization of a mono(ADP-ribosyl)transferase from
      human testis.
AB  - A human homologue of the rodent T cell mono(ADP-ribosyl)transferase RT6 mRNA was
      identified by a systematic partial sequencing of human testis transcripts. This
      messenger encodes for a precursor protein of 367 aa (MW: 41.5 kDa) which exhibits
      a peptide signal, consensus domains for mono(ADP-ribosyl)transferase and a C
      terminal part which contains three repeated motives (GEKNQKLEDH) and a region
      characteristic of glycophosphatidyl inositol anchored proteins. This mRNA is
      transcribed from a gene localized in 4q13-q21. Surprisingly, it is not expressed
      in human white blood cells but it exhibits a very specific testis expression in
      which it is likely to correspond to a new ADP-ribosyl transferase.

PMID- 9193646
TI  - Molecular cloning and characterization of arginine-specific ADP
      ribosyltransferases from chicken bone marrow cells.
AB  - Among a number of tissues and peripheral blood cells in chicken, leukocytes, bone
      marrow cells, liver and spleen showed high ADP-ribosyltransferase activity, with
      leukocytes having the highest. Density gradient centrifugation of the leukocytes
      revealed that the leukocyte ADP-ribosyltransferase originates in the
      polymorphonuclear cells, so called heterophils. Subcellular distribution of the
      cells showed the localization of the enzyme in the granule fraction. Based on the
      obtained amino acid sequences of arginine-specific ADP-ribosyltransferase
      purified from chicken peripheral heterophils, two arginine-specific ADP
      ribosyltransferase cDNAs (designated AT1 and AT2) were obtained from chicken bone
      marrow cells. Each cDNA encodes a different peptide of 312 amino acid residues.
      Homology of the deduced amino acid sequences between AT1 and AT2 was 78.3%.
      Arginine-specific ADP-ribosyltransferase activity was detected in culture medium
      of COS 7 cells transiently transfected with AT1 cDNA, while activity from the
      cells transfected with AT2 cDNA was found in both culture medium and cell lysate.
      AT1 transferase required 2-mercaptoethanol (MSH) for the activity and in the
      presence of NaCl, the activity was inhibited while the AT2 enzyme was activated
      by either agent. Highly conserved regions were observed among the deduced amino
      acid sequences of AT1, AT2, chicken erythroblast and rabbit and human skeletal
      muscle ADP-ribosyltransferases, and rodent T-cell surface antigen RT6. Two forms
      of the transferase with much the same properties as AT1 and AT2 proteins,
      regarding the effect of NaCl and MSH, were detected in bone marrow cells. Based
      on these results it seems that AT1 and AT2 cDNAs encode the two forms of arginine
      specific ADP-ribosyltransferase detected in chicken bone marrow cells.

PMID- 9193647
TI  - Purification, characterisation, and molecular cloning of a chicken erythroblast
      mono(ADP-ribosyl)transferase.
AB  - We have purified an arginine-specific mono(ADP-ribosyl)transferase from chicken
      erythrocytes. The purified transferase was free from poly (ADP-ribose) polymerase
      activity. The molecular weight of the purified enzyme was estimated to be 27.5
      kDa by gel filtration through Sephadex G-75 in a non-denaturing solvent. Activity
      gel experiments indicate that the active enzyme has an apparent molecular weight
      in SDS gels of about 28 kDa. The optimum pH of the reaction is about 8.0. The
      K(m) value for NAD+ of the purified enzyme is about 130 microM. Small molecular
      weight inhibitors of poly (ADP-ribose) polymerase have no significant effect on
      the mono ADP-ribosyl transferase enzyme activity. A number of inhibitors of the
      arginine-specific mono(ADP-ribosyl)transferase activity have been identified.
      Among the more effective inhibitors are 1,4 naphthoquinone, 5,8-dihydroxy-1,4
      naphthoquinone, 4-amino-1-naphthol and 1,2-naphthoquinone. We have also cloned a
      mono(ADP-ribosyl)transferase from chicken erythroblasts. This gene has been
      expressed in E. coli and ADP-ribosylation activity has been demonstrated using
      histones as substrate. The activity is shown to be arginine-specific by the use
      of poly-L-arginine as substrate. Use of a specific inhibitor has shown that this
      enzyme is indeed a mono(ADP-ribosyl)transferase and not a NAD glycohydrolase
      activity. The sequence of this gene is very similar to several other mono(ADP
      ribosyl)transferase genes. There are thus at least three different chicken
      mono(ADP-ribosyl)transferase genes in the blood system alone; this suggests that
      there is a quite large family of mono(ADP-ribosyl)transferase genes in animals.
      We have also isolated the promoter region of this chicken gene and are able to
      identify several standard motifs in this promoter.

PMID- 9193648
TI  - Molecular characterisation of a fungal mono(ADP-ribosyl)transferase.
AB  - A soluble arginine-specific mono(ADP-ribosyl)transferase was detected in dormant
      spores of Phycomyces blakesleeanus. Soluble proteins incubated with [32P]NAD
      revealed, after a two dimensional electrophoretic separation, three major ADP
      ribosylated substrates with molecular weights of 38, 37, and 36 kDa and pI values
      of 6.9, 8.1 and 4.6, respectively. The addition of MgCl2 stimulated the (ADP
      ribosyl)transferase activity. This enzymatic activity was stimulated by 250
      microM NO-releasing agent sodium nitroprusside and inhibited with 8 mM benzamide,
      0.4 mM meta-IodoBenzylGuanidine (MIBG), and 0.5 mM novobiocin. The three ADP
      ribosylation inhibitors affected the germination of Phycomyces spores. The
      concentrations necessary to inhibit 50% of the spore germination of Phycomyces
      were 0.05 mM, 0.2 mM, and 8 mM for novobiocin, MIBG, and benzamide, respectively.
      All the above inhibitors affected the germination process to the same extent,
      that is, they inhibited the tube protuberation, leaving the spores as swollen
      cells. These data suggest that ADP-ribosylation may be involved in the
      germination process of Phycomyces, particularly in germ-tube formation.

PMID- 9193649
TI  - Use of the EST database resource to identify and clone novel mono(ADP
      ribosyl)transferase gene family members.
AB  - We searched the database of expressed sequence tags (dbEST) for relatives of the
      known human and murine mono(ADP-ribosyl)transferases (mADPRT), poly(ADP
      ribosyl)polymerases (PARP), ADP-ribosyl cyclases, and ADP-ribosylarginine
      hydrolases (ARH). By May 31, 1996, all of the known enzymes except for RT6 were
      represented in dbEST by exact sequence matches from mouse and/or human tissues.
      Several ESTs show significant sequence similarity but not identity to known
      mADPRTs. We isolated, cloned, and sequenced the corresponding genes. Our results
      show that seven human ESTs stem from a novel gene, provisionally designated LART,
      which is specifically expressed in lymphatic tissues. Five human ESTs stem from a
      novel gene, here designated TART1, which is specifically expressed in testis.
      This gene is also represented by a single mouse EST. One other mouse EST stems
      from a distinct gene, here designated TART2, which is also expressed in testis.
      These genes have similar exon/intron structures. The predicted LART and TART1
      gene products contain hydrophobic N- and C-terminal signal peptides
      characteristic for GPI-anchored surface proteins, TART2 lacks the GPI-anchor
      signal peptide. The predicted native proteins show 28-42% sequence identity to
      one another. They each contain four cysteine residues that probably form
      conserved disulfide bonds. They each also contain a conserved glutamic acid
      residue within the proposed active site motif LART and TART1 show interesting
      deviations from the surrounding consensus sequence.

PMID- 9193650
TI  - Mouse RT6 locus 1 and rat RT6.2 are NAD+. Arginine ADP-ribosyltransferases with
      auto-ADP-ribosylation activity.
AB  - We report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto
      ADP-ribosyltransferase activity and that Rt6, but not RT6, catalyzes the ADP
      ribosylation of exogenous histones. Based on NH2OH sensitivity, it appeared that
      the ADP-ribose was attached to arginine residues on proteins. We also observed
      that the NAD+ concentration in culture medium correlates inversely with the
      proliferation of rat RT6+ T cells. The data suggest that lymphocyte surface ADP
      ribosyltransferases could be involved in signaling and immunoregulatory
      processes.

PMID- 9193651
TI  - Expression and comparative analysis of recombinant rat and mouse RT6 T cell
      mono(ADP-ribosyl)transferases in E. coli.
AB  - Recombinant RT6 proteins of rat and mouse were analyzed for NAD-metabolizing,
      i.e. mono(ADP-ribosyl)transferase, NAD-glycohydrolase (NADase) and ADP-ribosyl
      cyclase activities. The results reveal surprising intra- as well as inter-species
      differences in enzyme activities. While mouse Rt6 proteins were found to be
      strong arginine-specific transferases, but comparatively weak NADases, the
      opposite held true for rat RT6, for which transferase activity could only be
      detected in the form of arginine-specific auto-ADP-ribosylation, displayed by
      RT6.2 but not by RT6.1. NADase activity of rat RT6 was not accompanied by
      production of cyclic ADPR (cADPR). Rat RT6 gained potent arginine-specific
      transferase activity by exchange of a single amino acid for the corresponding
      residue of the mouse proteins.

PMID- 9193652
TI  - Molecular characterization of rat T lymphocyte alloantigen RT6.1 as an ADP
      ribosyltransferase.
AB  - A family of glycosylphosphatidylinositol-linked ADP-ribosyltransferases, of which
      cDNAs were cloned from various mammalian cells, possess a common Glu-rich motif
      (EEEVLIP) near their carboxyl termini. Although the first Glu in the common motif
      is replaced by Gln (Q207EEVLIP) in rat T lymphocyte alloantigens RT6.1 and RT6.2,
      the two RT6s appear to have ADP-ribosyltransferase activity. To investigate the
      significance of the Glu-rich motif in the enzyme activity, we produced a mutant
      RT6.1, in which Gln207 was replaced by Glu (Q207E), together with wild-type RT6s,
      in Escherichia coli. The recombinant RT6.1 and RT6.2 displayed extremely low auto
      ADP-ribosylation, though the latter modification was somewhat higher than the
      former one. In contrast, much higher the auto-modification was observed for Q207E
      mutant. Moreover, the mutant could effectively ADP-ribosylate agmatine as a
      substrate. Thus, the single amino acid mutation of RT6.1 caused remarkable
      increase in its ADP-ribosyltransferase activity, indicating that the Glu-rich
      motif near the carboxy terminus plays an important role in the enzyme activity.

PMID- 9193653
TI  - Using secondary structure predictions and site-directed mutagenesis to identify
      and probe the role of potential active site motifs in the RT6 mono(ADP
      ribosyl)transferases.
AB  - The RT6 T cell mono(ADP-ribosyl)transferases are expressed as GPI-anchored
      membrane proteins by mature T lymphocytes. We performed secondary structure
      prediction analyses of RT6 with a profile based neural network system based on
      multiple alignments of RT6 with other vertebrate mono(ADP-ribosyl)transferases
      (mADPRTs). The results reveal a linear order of predicted beta sheets/alpha helix
      in RT6 that are quite similar to those in the catalytic subunit of the four known
      crystal structures of mono-ADP-ribosylating bacterial toxins. Recognizable amino
      acid similarities occur throughout the region of predicted structural homology to
      the bacterial toxins. Three residues which have been shown to be important for
      catalysis in bacterial toxins (e.g. R9, S52 and E129 in pertussis toxin) occur in
      a similar context also in RT6 (R126, S147 and E189). We have mutated these
      residues in RT6 by site-directed mutagenesis. The RT6 mutants exhibit remarkably
      similar alterations in enzymatic phenotype as those reported for mutations of the
      proposed analagous residues in bacterial toxins. These results support the
      hypothesis that eu- and procaryotic mADPRTs share a common fold and have a common
      ancestry.

PMID- 9193654
TI  - Regulation of cytotoxic T cell functions by a GPI-anchored ecto-ADP
      ribosyltransferase.
AB  - Protein mono-(ADP-ribosyl)transferases (ADPRTs) catalyze transfer of the ADP
      ribose moiety from nicotinamide adenine dinucleotide (NAD) to specific amino
      acids. We recently described presence of an enzyme with this activity on
      cytotoxic T cells (CTL). Incubation of CTL with micromolar concentrations of NAD
      causes inhibition of cell proliferation and cytolytic activity. ADPRT can be
      released by bacterial phosphoinosital specific phospholipase C, indicating that
      it is a glycosylphosphatidylinositol (GPI) anchored exo-enzyme. Enzymatic release
      of ADPRT results in inability of NAD to modulate CTL function. Expression of
      ADPRT was found to be regulated, in quiescent CTL ADPRT is expressed at
      significant levels, however, upon TCR crosslinking it is rapidly released by an
      anchor hydrolyzing mechanism. This results in relative insensitivity to the
      inhibitory action of NAD. The question how ADPRT regulates T cell functions was
      investigated by incubating CTL with radioactively labeled NAD which causes
      modification of several proteins, pointing to potential candidates in these
      regulatory processes. We found that the protein tyrosine kinase p56lck but not
      p59fyn exists in a digitonin resistant complex with a 40 kD protein, which in its
      ADP-ribosylated form suppresses p56lck kinase activity. ADP-ribosylation of this
      protein is mediated by the arginine specific protein mono-ADPRT, presumably
      utilizing ecto-NAD as substrate. Release of the ADPRT by GPI-specific
      phospholipase C results in failure of ecto-NAD to downmodulate p56lk kinase
      activity. Concomitant to suppression of the kinase by ecto-NAD, CD8 mediated
      transmembrane signaling is found to be inhibited, whereas transmembrane signaling
      via CD3 is only slightly affected.

PMID- 9193655
TI  - Effects of inhibitors of ADP-ribosylation on macrophage activation.
AB  - Nitric oxide (NO) is a potent mediator involved in many biological functions
      including macrophage cytotoxicity and non-specific immunity against parasites,
      bacteria and viruses. Murine macrophages possess the capacity to express the
      inducible NO synthase (iNOS) which is not constitutively expressed but induced at
      the transcriptional level by interferon gamma (IFN-gamma) alone or
      synergistically with LPS. We have investigated the possible role of ADP
      ribosylation reactions in the signaling pathway involved in NO synthase
      induction, since ADP-ribosylation has been reported to be involved in the
      expression of certain IFN-gamma and LPS-inducible genes. We found that inhibitors
      of ADP-ribosylation inhibited nitrite synthesis in RAW 264.7 macrophages after
      stimulation by IFN-gamma and LPS. These ADP-ribosylation inhibitors acted by
      preventing NO synthase mRNA induction, without inhibiting NO synthase enzyme
      activity. IRF-1, a transcription factor induced and activated by IFN-gamma was
      recently shown to be involved in iNOS induction. We showed that inhibitors of ADP
      ribosylation had no effect on IFN-gamma-mediated mRNA induction of IRF-1 nor on
      its activation and binding to its target sequence in the iNOS gene. In addition,
      the inhibitors failed to impair the IFN-gamma-mediated antiviral activity against
      VSV virus. Since induction by IFN-gamma of IRF-1 and induction of the antiviral
      state proceed through the JAK/STAT signalling pathway, our results imply that ADP
      ribosylation reactions are not involved in triggering this pathway. Although the
      precise mechanism requires further investigation, our results indicate that ADP
      ribosylation is a crucial step restricted to the signalling pathway which leads
      to iNOS mRNA induction, as well as TNF and MHC class II induction during
      macrophage activation.

PMID- 9193656
TI  - The T cell marker RT6 in a rat model of autoimmune diabetes.

PMID- 9193657
TI  - Mono(ADP-ribosyl)transferase genes and diabetes in NOD mice. Is there a
      relationship?
AB  - The answer to the question posed by the title (is there a relationship between
      aberrant Art gene expression and IDDM pathogenesis in NOD mice?) remains elusive.
      Conclusions are currently based almost entirely upon analysis of mRNA transcript
      levels rather than on T-cell-specific mono-ADP ribosylation activities. Our
      unpublished data, as well as data published in abstract form by Dr. L. Chatenoud
      and colleagues (48) indicate that gene transcription is not impaired in splenic
      leukocytes of older NOD mice, including those with spontaneous IDDM development.
      Based upon the limited data showing that there may be reduced expression of Art
      gene products in the earliest T cell immigrants from the NOD thymus, one would
      have to surmise that If there is a regulatory defect, it may be in allowing
      single positive thymic T cells to emigrate before they are fully mature.
      Therefore, development of anti-Art monoclonal antibody together with further
      studies regarding functions of mono(ADP-ribosyl)transferase in immunoregulation
      of different subpopulation of T-cells, may finally resolve the role that altered
      mono(ADP-ribosyl)transferase activities play in the pathogenesis of IDDM in NOD
      mice.

PMID- 9193659
TI  - Arginine-specific mono(ADP-ribosyl)transferase activity in human neutrophil
      polymorphs. A possible link with the assembly of filamentous actin and
      chemotaxis.
AB  - Mono(ADP-ribosyl)transferase activity has been detected on the external surface
      of human polymorphonuclear neutrophil leucocytes (PMNs). The corresponding cDNA
      has been cloned and shown to be identical to that derived from human skeletal
      muscle. Our results suggest that mono(ADP-ribosyl)transferase is involved in the
      transduction pathway mediating (i) receptor-dependent re-alignment of
      cytoskeletal actin and (ii) chemotaxis of PMNs.

PMID- 9193658
TI  - Expression of the ectoenzyme RT6 is not restricted to resting peripheral T cells
      and is differently regulated in normal peripheral T cells, intestinal IEL, and NK
      cells.
AB  - The RT6 alloantigenic system of the rat has originally been defined on T
      lymphocytes of the peripheral lymphatic organs and has been considered to be
      selectively expressed on mature peripheral T cells. Studying NK cells and
      intestinal intraepithelial lymphocytes (IEL), we have now found that both cell
      types also express RT6 and that the expression patterns found for IEL and NK
      cells were markedly different from each other and also from the expression
      pattern previously described for T cells of the peripheral lymphatic organs. In
      lymph nodes, spleen, and blood both RT6- and RT6+ T cells have been found and the
      density of RT6 expression on the positive cells has been shown to vary over a
      broad range. In contrast more than 98% of intestinal IEL stained for RT6 and the
      RT6 density was about tenfold higher than on strongly positive T cells of the
      peripheral lymphatic organs. Furthermore, the same high RT6 density was also
      found on IEL of athymic nude rats althogh these cells, to a large extent, lacked
      other T cell markers. This probably indicates that RT6 expression is an early
      event in the maturation of intestinal IEL which can occur already before the
      expression of T cell-specific membrane molecules. The conclusion that the
      expression of RT6 may be differently regulated in IEL and other T cell
      populations was further substantiated by the observation that RT6 was also
      present on IEL of diabetes-prone BB rats which are known to lack RT6 positive T
      cells in peripheral lymphatic organs. For NK cells still another pattern of RT6
      expression was found. Unlike peripheral T cells and IEL, only a small subset of
      NK cells in blood and spleen expressed RT6. The percentage of RT6 positive cells
      was increased by in vitro stimulation of isolated NK cells with high
      concentrations of recombinant rat IL-2 indicating that RT6 expression may be
      associated with an activated state in NK cells. Taken together, these findings
      demonstrate that the expression of RT6 is not restricted to T cells and is
      differently regulated in normal peripheral T cells, intestinal IEL, and NK cells.
      Since it has recently been demonstrated that the RT6 gene contains two functional
      promoter regions with major structural disparity it is very likely that the
      distinct patterns of RT6 expression in different cell types reflect the
      differential use of the two promoters. The development of this complex control of
      RT6 expression in evolution may have been driven by a beneficial effect resulting
      from the use of the RT6 molecular function by several different lymphocyte
      populations.

PMID- 9193660
TI  - A newly identified glycosylphosphatidylinositol-anchored arginine-specific ADP
      ribosyltransferase in chicken spleen.
AB  - An arginine-specific ADP-ribosyltransferase activity was detected in chicken
      spleen membrane fraction using a capillary electrophoresis assay and the activity
      was extracted by phosphatidylinositol-specific phospholipase C but not by 1 M
      NaCl or 1% Triton X-100. The enzyme protein was purified from chicken spleen
      membrane fraction to apparent homogeneity with a six-step method containing
      phosphatidylinositol-specific phospholipase C treatment, ammonium sulfate
      precipitation and conventional column chromatographies. Apparent molecular mass
      of the purified enzyme estimated with SDS/PAGE was 44 kDa. N-glycanase treatment
      of the enzyme reduced the apparent molecular size on SDS/PAGE. The enzyme was
      recognized by anti-cross reacting determinant antibodies. Partial amino acid
      sequence of the purified enzyme protein showed high homologies with primary
      structures of previously reported chicken arginine-specific ADP
      ribosyltransferases.

PMID- 9193661
TI  - Role of ADP-ribosylation in activated monocytes/macrophages.
AB  - Stimulating monocytes/macrophages with bacterial lipopolysaccharide (LPS) results
      in TNF-alpha, IL-1, IL-6 and nitrite (NO2-) formation. Inhibitors of poly(ADP
      ribose)polymerase inhibit release of these mediators by preventing mRNA
      expression indicating that ADP-ribosylation plays a crucial role in the synthesis
      of these mediators. Furthermore we present evidence that ADP-ribosylation is
      involved in modifying cellular proteins. In murine macrophages a 33 kDa cytosolic
      protein could be identified that in response to LPS changed its state of ADP
      ribosylation, and in human monocytes we showed that the inhibitor nicotinamide
      prevents LPS induced phosphorylation of two cytosolic proteins of 36 kDa and 38
      kDa (p36/38) LPS. Taken together these data indicate that protein modification by
      ADP-ribosylation may control cellular processes involved in distinct steps of
      monocyte/macrophage activation.

PMID- 9193662
TI  - Expression of RT6, but not CD45RC, is disturbed on immature peripheral T cells in
      the BB rat.

PMID- 9193663
TI  - Expression of RT6 on activated rat T cells.
AB  - The gene products of the RT6 system have been demonstrated to be expressed on the
      majority of resting peripheral T cells but not on fully activated cytotoxic T
      cells and in vitro generated long term T cell lines. This has lead to the
      conclusion that T cell activation causes a loss of RT6 expression. In the present
      study this question was examined by analysing the expression of RT6 on T cell
      populations activated in vitro by the T cell mitogen ConA or by allogeneic
      stimulator cells and subsequently maintained in culture for several weeks. The
      results showed an initial increase in RT6 expression on most cells during the
      first two days of culture and a subsequent loss of RT6 expression in many
      activated cells. Substantial numbers of both CD4+ and CD8+ T cells, however,
      remained clearly RT6 positive. These cells were present during the entire
      observation period. The RT6 positive cells did not represent persisting
      unstimulated cells since they coexpressed CD25 and exhibited typical blast
      morphology. It is concluded that activation of T cells leads to loss of RT6
      expression only in subsets of the CD4 and CD8 T cell populations. The previously
      reported finding that long term cultures contain only RT6 negative blast cells
      may indicate preferential survival of RT6 negative blasts rather than obligatory
      loss of RT6 expression after activation. The possibility is discussed that
      activated RT6-CD4+ T cells may be inflammatory Th1 cells and activated RT6+CD4+ T
      lymphoblasts may represent regulatory Th2 cells.

PMID- 9193664
TI  - Expression of the RT6 mono(ADP-ribosyl)transferases is regulated by two promoter
      regions.
AB  - The structure of the RT6 mono(ADP-ribosyl)transferase gene was studied. Analysis
      of cDNA clones revealed eight exons and suggested two independent transcriptional
      start sites. The existence of the downstream initiation site was confirmed by S1
      nuclease protection and localized to position +29 of exon 2. The corresponding 5'
      flanking regions were found to contain typical promoter structures such as TATA-
      and CCAAT-boxes. Comparison with sequences deposited in the TRANSFAC database of
      transcription factor binding sites revealed few putative regulatory elements in
      the region associated with exon 1 (promoter 1). In contrast, several elements
      contained in the regulatory regions of other T cell-specific genes, such as ets,
      lyf-1 and ikaros were found in in promoter 2. Analysis of RT6-transcripts showed
      this region to be the most active promoter in spleen cells of adult rats.
      Finally, transient transfection assays with reporter gene constructs showed
      promoter 2 to mediate T-cell specific transcription.

PMID- 9193665
TI  - "Natural" RT6-1 and RT6-2 "knock-out" mice.
AB  - We have screened different mouse strains-including strains with enhanced
      susceptibility for autoimmune diseases-for deviations of Rt6 gene expression by
      RT-PCR. Most strains expressed varying amounts of Rt6-1 and Rt6-2. NZW mice,
      however, do not show any detectable Rt6-2 gene transcripts. BxSB mice show a near
      complete absence of Rt6-1 gene transcripts. Southern blot and sequence analyses
      revealed that NZW mice have suffered a deletion of the Rt6.2 gene while the Rt6-1
      gene of BxSB mice has been inactivated by a premature stop codon. Thus, these
      mouse strains represent natural Rt6-2 and Rt6-1 single-gene 'knock-out's,
      respectively. Since the NZW mouse does not show any gross immunological
      abnormalities, loss of the Rt6-2 gene by itself is not associated with any
      obvious immunological phenotype. However, crosses between NZW and certain other
      mouse strains, e.g. (NZW x NWB)F1 and (NZW x SB)F1 animals, develop a systemic
      autoimmune disease reminiscent of human lupus erythematosus. Moreover, the BxSB
      mouse strain is considered to be an independent model for the same disease. It
      will be of interest to determine whether these spontaneous Rt6 gene defects
      constitute part of the polygenetic contribution to autoimmune disease in these
      animals.

PMID- 9193667
TI  - Endogenous ADP-ribosylation of phosphoprotein B-50/GAP-43 and other neuronal
      substrates.

PMID- 9193666
TI  - An ADP-ribosyltransferase from bovine erythrocytes apparently specific for
      cysteine residues.
AB  - An NAD+:cysteine glycohydrolase purified from bovine erythrocytes had a specific
      activity of 1900 (nmol nicotinamide released).min-1.mg-1, a K(m) for cysteine of
      4.0 mM, and an M, of 45,000. The enzyme also catalysed the dose-dependent ADP
      ribosylation of several bovine erythrocyte proteins, including a doublet of high
      M(r) and proteins of M(r) 60,000, 55,000, and 29,000. ADP-ribosylation of the
      M(r) 55,000 protein was blocked by pre-treatment of the erythrocyte membranes
      with N-ethylmaleimide, and ADP-ribose was released by treatment with mercuric
      ions, but not with hydroxylamine. The enzyme therefore appears to be a cysteine
      specific ADP-ribosyltransferase.

PMID- 9193668
TI  - Endogenous mono-ADP-ribosylation in retina and peripheral nervous system. Effects
      of diabetes.
AB  - The extranuclear endogenous mono-ADP-ribosylation of proteins was monitored in
      cellular preparations of retina, superior cervical ganglion, dorsal root ganglia
      and peripheral nerve. At least 6 protein fractions are ADP-ribosylated in the
      crude extract fraction from retina control preparations, while in diabetic rats
      the number of retina labeled proteins and the extent of labeling are highly
      reduced. In the superior cervical ganglion labeling was present in 10 proteins,
      in diabetics it was greatly decreased. Treatment of diabetic rats with silybin, a
      flavonoid mono-ADP-ribosyltransferase inhibitor, did not affect hyperglycemia,
      but prevented the alteration of extent of protein ADP-ribosylation. These data
      suggest that proteins of retina and peripheral ganglia are excessively ADP
      ribosylated in vivo. The effects of silybin treatment on excessive mono-ADP
      ribosylation of proteins was associated with the prevention of reduction of
      substance P-like immunoreactivity levels, that is typical of diabetic neuropathy.
      In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were
      ADP-ribosylated, diabetes caused a marked increase of labeling. A comparable
      increase involving the same proteins is triggered by chronic nerve injury and by
      corticosteroid treatment. Silybin treatment of diabetic rats prevented such an
      increase. We propose that the inhibition of excessive protein mono-ADP
      ribosylation by silybin prevented the onset of diabetic neuropathy. While the
      effects on Schwann cells is likely indirect and secondary to the improvement of
      diabetic axonopathy.

PMID- 9193669
TI  - The alpha 7 integrin as a target protein for cell surface mono-ADP-ribosylation
      in muscle cells.
AB  - A membrane-associated arginine-specific mono-ADP-ribosyltransferase was purified
      215,000-fold from rabbit skeletal muscle and its gene was isolated from a
      skeletal muscle cDNA library. The enzyme was a glycosylphosphatidyl-inositol
      linked protein, present on the surface of differentiated skeletal muscle
      myoblasts (myotubes). Following incubation of cultured, intact myotubes with
      [adenylate-32P]NAD and analysis by SDS-PAGE, a major radiolabeled protein of
      97/140 kDa (reduced/nonreduced conditions) was observed. It was identified as
      integrin alpha 7 based on its size, binding to a laminin affinity column,
      immunoprecipitation with a monoclonal antibody, and partial amino acid
      sequencing. Since ADP-ribosylarginine hydrolase, the enzyme responsible for
      cleavage of the ADP-ribosylarginine bond and a component with the transferase of
      a putative ADP-ribosylation cycle, is cytosolic, whereas the transferase is
      attached via a GPI-anchor to the cell surface, the processing of ADP-ribosylated
      integrin alpha 7 was investigated. 32P label was rapidly removed from [32P]ADP
      ribosylated integrin alpha 7, a process inhibited by free ADP-ribose or p
      nitrophenylthymidine-5'-monophosphate, alternative substrates for 5'-nucleotide
      phosphodiesterase. The processed integrin alpha 7 was not susceptible to
      subsequent ADP-ribosylation, although the amount of surface integrin alpha 7
      remained constant. During the processing, no loss of label was observed from
      integrin alpha 7 radiolabeled with [14C]NAD, containing 14C in the nicotinamide
      proximal ribose, consistent with a degradation of the ADP-ribose moiety by a cell
      surface 5'-nucleotide phosphodiesterase. Thus, cell surface ADP-ribosylation, in
      contrast to intracellular ADP-ribosylation, is not readily reversed by the
      presently known ADP-ribosylarginine hydrolase and seems to operate outside the
      postulated ADP-ribosylation cycle.

PMID- 9193670
TI  - Regulatory role of arginine-specific mono(ADP-ribosyl)transferase in muscle
      cells.
AB  - Earlier we demonstrated that meta-iodobenzylguanidine (MIBG), a specific
      inhibitor of arginine mono-ADP-ribosylation blocks proliferation and
      differentiation of chick skeletal myogenic cells in culture (Exp. Cell Res.,
      1992, 201:33-42). Membrane fractions from 4-day, myotube cultures of embryonic
      chick muscle cells were incubated with 32P-NAD+. Several proteins were labeled,
      but labeling of two hands of about 53 and 36 kDa appeared to be due to arginyl
      ADP-ribosylation. Immunoprecipitation with D3 monoclonal antibody to the
      intermediate filament protein desmin, SDS-PAGE and autoradiography demonstrated
      that the 53 kDa band contained desmin, and that this desmin is ADP-ribosylated by
      the endogenous arginine-specific mono(ADP-ribosyl)transferase (Exp. Cell Res.,
      1996, in press). Desmin is the muscle-specific intermediate filament protein, and
      it appears to be one of the first muscle-specific proteins expressed during
      terminal myogenic differentiation. We have examined whether desmin can be ADP
      ribosylated in muscle cells by use of polyclonal antibodies for ADP-ribosylated
      arginyl residues. We have found that soluble desmin is present in 5-6 day
      myogenic cell cultures and that this desmin contains ADP-ribose, demonstrating
      that desmin is ADP-ribosylated in skeletal muscle cells. We also found that
      purified avian desmin contains antigenic material that reacts with these
      antibodies. In both cases, NaCl had no effect on the reactivity, but NH2OH did,
      which is consistent with an arginine-ADPR linkage. In summary, these results
      suggest that ADP-ribosylation is an important regulatory mechanism in
      differentiating muscle cells, and that the intermediate filament protein desmin
      is an important substrate for modification in muscle cells.

PMID- 9193671
TI  - Activation of toxin ADP-ribosyltransferases by the family of ADP-ribosylation
      factors.
AB  - ADP-ribosylation factors or ARFs are 20-kDa guanine nucleotide-binding proteins,
      initially identified as stimulators of cholera toxin-catalyzed ADP-ribosylation
      of Gs alpha. We now know that ARFs play a critical role in many vesicular
      trafficking events and ARF activation of a membrane-associated phospholipase D
      (PLD) has been recognized. ARF is active and associates with membranes when GTP
      is bound. The active state is terminated by hydrolysis of bound GTP, producing
      inactive ARF-GDP. The nucleotide effect on ARF association with membranes is
      related to alteration in orientation of the N-terminal myristoyl moiety that is
      important for ARF function. Cycling of ARF between active and inactive states
      involves guanine nucleotide-exchange proteins (GEPs) that accelerate replacement
      of bound GDP with GTP and GTPase-activating proteins (GAPS) that are responsible
      for ARF inactivation. Six mammalian ARFs have been identified by cDNA cloning.
      Class I ARFs 1 and 3 have been studied most extensively. Their activation (GTP
      binding) is catalyzed by a GEP now purified from spleen cytosol. In crude
      preparations, GEP was inhibited by brefeldin A (BFA), which in cells causes
      apparent disintegration of Golgi. Demonstration that the approximately 60 kDa
      purified GEP was not inhibited by BFA means that contrary to earlier belief,
      there must be another protein to mediate BFA inhibition. GEP activity was greatly
      enhanced by phosphatidyl serine. The purified GEP, equally active with ARFs 1 and
      3, was inactive with ARFs 5 and 6 (Classes II and III); myristoylated ARFs were
      better substrates than were their non-myristoylated counterparts. ARF GAP
      purified from bovine spleen cytosol in our laboratory had much broader substrate
      specificity than the GEP. It used both ARFs 5 and 6 at least as well as ARFs 1
      and 3; myristoylation was without effect. It also accelerated GTP hydrolysis by
      certain ARF mutants and an ARF-like protein (ARL1) that does not have ARF
      activity. The purified GAP also differed from the GEP in its rather specific
      requirement for phosphatidylinositol bisphosphate. This was also observed with a
      seemingly different ARF GAP that was purified and subsequently cloned in Cassel's
      laboratory. Activation and inactivation of ARFs present many potential sites for
      physiological regulation and, therefore, for pathological disruption of ARF
      function.

PMID- 9193672
TI  - Possible role of BARS-50, a substrate of brefeldin A-dependent mono-ADP
      ribosylation, in intracellular transport.
AB  - Brefeldin A (BFA), a fungal metabolite that inhibits membrane transport, potently
      stimulates an endogenous ADP-ribosylation reaction that selectively modifies two
      cytosolic proteins of 38 and 50 kDa on an amino acid residue different from those
      used by all known mADPRTs. The 38-kDa substrate was identified as the glycolytic
      enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), whereas the 50-kDa
      substrate (BARS-50) was characterized as a novel guanine nucleotide binding
      protein. Thus, BARS-50 is able to bind GTP and its ADP-ribosylation is inhibited
      by the beta gamma subunit of GTP-binding (G) proteins. Moreover, BARS-50 was
      demonstrated to be a group of closely related proteins that appear to be
      different from all the known G proteins. A partially purified BARS-50 was
      obtained from rat brain cytosol, which was then used for microsequencing and in
      functional studies. A similar procedure led to the purification of native (non
      ADP-ribosylated) BARS-50. The possible role of the BFA-dependent ADP-ribosylation
      and of BARS-50 in the maintenance of Golgi structure and function was addressed
      by examining which of the effects of BFA may be modified by inhibiting this
      reaction. We find that the BFA-dependent transformation of the Golgi stacks into
      a tubular reticular network is prevented when the BFA-dependent ADP-ribosylation
      activity was blocked by specific inhibitors thus indicating that BFA-dependent
      ADP-ribosylation of cytosolic proteins participate in the dynamic regulation of
      intracellular transport.

PMID- 9193673
TI  - Brefeldin A-induced ADP-ribosylation in the structure and function of the Golgi
      complex.
AB  - Brefeldin A (BFA) is a fungal metabolite that exerts generally inhibitory actions
      on membrane transport and induces the disappearance of the Golgi complex.
      Previously we have shown that BFA stimulates the ADP-ribosylation of two
      cytosolic proteins of 38 and 50 KD. The BFA-binding components mediating the BFA
      sensitive ADP-ribosylation (BAR) and the effect of BFA on ARF binding to Golgi
      membranes have similar specificities and affinities for BFA and its analogues,
      suggesting that BAR may have a role in the cellular effects of BFA. To
      investigate this we used the approach to impair BAR activity by the use of BAR
      inhibitors. A series of BAR inhibitors was developed and their effects were
      studied in RBL cells treated with BFA. In addition to the common ADP-ribosylation
      inhibitors (nicotinamide and aminobenzamide), compounds belonging to the cumarin
      (novobiocin, cumermycin, dicumarol) class were active BAR inhibitors. All BAR
      inhibitors were able to prevent the BFA-induced redistribution of a Golgi marker
      (Helix pomatia lectin) into the endoplasmic reticulum, as assessed in
      immunofluorescence experiments. At the ultrastructural level, BAR inhibitors
      prevented the tubular-vesicular transformation of the Golgi complex caused by
      BFA. The potencies of these compounds in preventing the BFA effects on the Golgi
      complex were similar to those at which they inhibited BAR. Altogether these data
      support the hypothesis that BAR mediates at least some of the effects of BFA on
      the Golgi structure and function.

PMID- 9193674
TI  - Characterization of the endogenous mono-ADP-ribosylation stimulated by brefeldin
      A.
AB  - We have recently described a novel enzymatic mono-ADP-ribosyl transfer reaction
      induced by brefeldin A, a well characterized inhibitor of vesicular traffic,
      which selectively modifies two cytosolic proteins of 38 kDa (p38) and 50 kDa
      (BARS-50). p38 was identified as glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH), a glycolytic enzyme and a multifunctional protein involved in several
      cellular processes; BARS-50 might be a novel G protein, since it is able to bind
      GTP and the beta gamma subunit of G proteins. We have characterized this
      enzymatic activity and screened in vitro the effects of different drugs belonging
      to the coumarine (dicumarol, coumermicin A1 and novobiocin) and quinone
      (ilimaquinones, benzoquinones and naphtoquinones) class. These drugs blocked the
      BFA-dependent mono-ADP-ribosylation, showed remarkable effects on Golgi
      morphology in control cells, and antagonized the tubular reticular redistribution
      of the Golgi complex in brefeldin A treated cells (see papers of Corda and
      Colanzi in this issue) suggesting a possible role for ADP-ribosylation in both
      the cellular effects of brefeldin A and the maintenance of the structure/function
      of the Golgi complex.

PMID- 9193675
TI  - Modulatory role of GTP-binding proteins in the endogenous ADP-ribosylation of
      cytosolic proteins.
AB  - The endogenous ADP-ribosylation of cytosolic proteins and the pattern of NAD
      degradation were analyzed in subcellular fractions of rat liver in order to
      investigate the modulation of these reactions by GTP-binding (G) proteins. We
      could show that intracellular membranes from rat liver have a guanine nucleotide-
      and divalent cation-dependent pyrophosphatase activity able to rapidly degrade
      NAD to AMP. This enzymatic activity was investigated by two different approaches:
      the degradation of [32P]-NAD in the presence of intracellular membranes and the
      mono-ADP-ribosylation of cytosolic proteins. Divalent cations, preferentially
      Zn2+ and Mn2+, were required for the pyrophosphatase activity, since in the
      presence of the Zn2+ chelator TPEN (N,N,N',N'-tetrakis(2-pyridyl
      methyl)ethylenediamine) or EDTA, the NAD degradation was inhibited by about 50%.
      Accordingly, in the presence of TPEN the endogenous ADP-ribosylation of cytosolic
      proteins was enhanced, whereas Zn2+ caused a significant inhibition of this
      reaction. GDP beta S was able to strongly activate the mono-ADP-ribosylation of
      cytosolic proteins. This effect was abolished by GTP gamma S, suggesting that a G
      protein, or rather one of the subunits of a heterotrimeric G protein, is involved
      in the modulation of the pyrophosphatase and consequently, of endogenous ADP
      ribosylation. We propose that a regulatory pathway involving a heterotrimeric G
      protein modulates enzymes affecting the NAD turnover and availability of NAD for
      endogenous mADPRTs.

PMID- 9193676
TI  - ADP-ribosylating and glucosylating toxins as tools to study secretion in RBL
      cells.
AB  - The influence of different ADP-ribosylating and glucosylating cytotoxins on
      stimulated protein tyrosine phosphorylation and secretion in rat basophilic
      leukemia (RBL) cells was studied. Treatment of RBL cells with Clostridium
      botulinum C2 toxin, which specifically ADP-ribosylated monomeric G-actin and
      caused complete depolymerization of the actin cytoskeleton in intact cells,
      inhibited Fc epsilon RI receptor-mediated tyrosine phosphorylation of various
      proteins in a time- and concentration-dependent manner with maximal effects at
      100 ng/ml C2I and 200 ng/ml C2I. C2 toxin (10 ng/ml C2I and 20 ng/ml C2II)
      increased antigen- or calcium ionophore (A23187)-stimulated [3H]serotonin release
      maximally by about 3 fold. Clostridium botulinum C3, which ADP-ribosylated Rho in
      intact RBL cells, had no effect on protein tyrosine phosphorylation and
      stimulated secretion. In contrast, the cytotoxic Clostridium difficile toxin B
      (ToxB), which glucosylated the Rho-subtype family members RhoA and Cdc42, blocked
      or reduced antigen- or calcium ionophore-mediated [3H]serotonin release,
      respectively, and decreased tyrosine phosphorylation of a 110 kDa protein. The
      data indicate that different actin pools control tyrosine phosphorylation and
      secretion in RBL cells and suggest that Rho subfamily proteins regulate secretion
      independently of the actin cytoskeleton.

PMID- 9193678
TI  - Signal transduction via GPI-anchored membrane proteins.

PMID- 9193677
TI  - Cell surface dynamics of GPI-anchored proteins.
AB  - Several cell surface eukaryotic proteins have a glycosylphosphoinositol lipid
      (GPI) modification at the carboxy-terminal end that serves as their sole means of
      membrane anchoring. In this report we review recent observations regarding the
      surface dynamics of GPI-anchored proteins. We discuss the association of GPI
      anchored proteins with caveolae at the cell surface and their role in signal
      transduction as determined by the ability of GPI-anchored proteins to form
      detergent-insoluble complexes enriched in several cytoplasmic proteins including
      non-receptor type tyrosine kinases and caveolin/VIP-21, a component of the
      striated coat of caveolae. We have shown by immunofluorescence and electron
      microscopy that GPI-anchored proteins are not constitutively concentrated in
      caveolae but may be enriched in these structures only after cross-linking. While
      caveolae occupy only a small fraction of the cell surface (< 4%) almost all of
      the GPI-anchored protein at the cell surface becomes incorporated into detergent
      insoluble low-density complexes, suggesting that these proteins are intrinsically
      detergent-insoluble in the milieu of the plasma membrane, and their co
      purification with caveolin is not reflective of their native distribution. The
      finding that GPI-anchored proteins are not normally clustered over caveolae
      raised questions about the involvement of caveolae in the internalization of GPI
      anchored proteins. In recent studies we have found that GPI-anchored proteins are
      internalized into bona fide endosomes wherein they appear to be sorted from bulk
      membrane components. The implications of these observations on the biology of GPI
      anchored proteins are discussed.

PMID- 9193679
TI  - ADP-ribose in glycation and glycoxidation reactions.
AB  - Glycation is initiated by reaction of a reducing sugar with a protein amino group
      to generate a Schiff base adduct. Following an Amadori rearrangement to form a
      ketoamine adduct, a complex chemistry involving oxidation often leads to protein
      glycoxidation products referred to as advanced glycosylation end products (AGE).
      The AGE include protein carboxymethyllysine (CML) residues and a heterogeneous
      group of complex modifications characterized by high fluorescence and protein
      protein cross links. The sugar sources for the glycoxidation of intracellular
      proteins are not well defined but pentoses have been implicated because they are
      efficient precursors for the formation of the fluorescent AGE, pentosidine. ADP
      ribose, generated from NAD by ADP-ribose transfer reactions, is a likely
      intracellular source of a reducing pentose moiety. Incubation of ADP-ribose with
      histones results in the formation of ketoamine glycation conjugates and also
      leads to the rapid formation of protein CML residues, histone H1 dimers, and
      highly fluorescent products with properties similar to the AGE. ADP-ribose is
      much more efficient than other possible pentose donors for glycation and
      glycoxidation of protein amino groups. Recently developed methods that
      differentiate nonenzymic modifications of proteins by ADP-ribose from enzymic
      modifications now allow investigations to establish whether some protein
      modifications by monomers of ADP-ribose in vivo represent glycation and
      glycoxidation.

PMID- 9193681
TI  - Hydrophobic properties of NAD glycohydrolase from neurospora crassa conidia and
      interaction with dioxane.
AB  - NAD glycohydrolase (NADase, EC 3.2.2.5) from Neurospora crassa conidia shows
      marked hydrophobic properties which are related to the self inhibition of the
      enzyme. Both aliphatic amines and carboxylic acids are able to inhibit
      noncompetitively the catalytic activity of the enzyme and the inhibition depends
      on the non-polar moiety of the substances. Also dioxane is an inhibitor of NAD
      glycohydrolase even though it apparently increases the specific activity of the
      enzyme. This effect can be explained by the fact that NADase is present as a
      dimer when the enzyme is concentrated or at high temperature, and dioxane binds
      the enzyme breaking the hydrophobic bonds in the dimeric enzyme and yielding the
      most active monomeric form which is only slightly inhibited by the organic
      solvent.

PMID- 9193680
TI  - Intramolecular ADP-ribose transfer reactions and calcium signalling. Potential
      role of 2'-phospho-cyclic ADP-ribose in oxidative stress.
AB  - Intramolecular ADP-ribose transfer reactions result in the formation of cyclic
      ADP-ribose (cADPR) and 2'-phospho-cyclic ADP-ribose (P-cADPR) from NAD and NADP,
      respectively. The potent Ca2+ releasing activity of these cyclic nucleotides has
      led to the postulation that they function as second messengers of Ca2+
      signalling. The synthesis and hydrolysis of cADPR and P-cADPR are catalyzed by
      NAD(P) glycohydrolases, but the metabolic signals that regulate their metabolism
      are poorly understood. To investigate the physiological roles of cADPR and P
      cADPR, it is essential to have methods that allow the routine measurement of
      these nucleotides in cellular systems. As described here, a sensitive and
      selective radioimmunoassay (RIA) for cADPR has been adapted to search for the
      natural occurrence of P-cADPR in mammalian tissues. Perchloric acid extracts
      prepared from bovine tissues and purified by anion exchange chromatography were
      found to contain immunoreactive material which was identified as P-cADPR. P-cADPR
      may play an important role in oxidative stress as a link between NADP(H)
      metabolism and alteration of intracellular Ca2+ homeostasis.

PMID- 9193682
TI  - Involvement of bovine spleen NAD+ glycohydrolase in the metabolism of cyclic ADP
      ribose-mechanism of the cyclization reaction.
AB  - We have shown that highly purified bovine spleen NAD+ glycohydrolase (NADase),
      known so far to catalyze the hydrolysis of the nicotinamide-ribose bond of
      NAD(P)+, was also able to convert NAD+ into cyclic ADP-ribose (cADPR) and to
      hydrolyze cADPR into ADP-ribose. The kinetic parameters measured for the cyclic
      ADP-ribose hydrolase activity seem to exclude that cADPR is a kinetically
      competent reaction intermediate in the NADase catalyzed conversion of NAD+ into
      ADP-ribose. The cyclase activity of bovine NADase was best evidenced by the
      transformation of NGD+ into cyclic GDP-ribose which was the major reaction
      product whereas, in contrast, cADPR accounted for less than 2% of the products
      formed. For the formation of cADPR we propose a reaction mechanism that is based
      on the partitioning of an oxocarbenium reaction intermediate between an
      intramolecular attack by the N1-position of adenine and an intramolecular
      reaction by a water molecule. Accordingly, the difference in cyclization between
      NAD+ and NGD+ is accounted for by the difference in reactivity of the N1 and N7
      positions of the purine ring in these dinucleotides.

PMID- 9193683
TI  - ADP-ribosyl cyclase and CD38. Multi-functional enzymes in Ca+2 signaling.
AB  - Mobilization of internal Ca+2 is an important signaling mechanism in cells. In
      addition to the inositol trisphosphate pathway, cyclic ADP-ribose (cADPR) and
      nicotinic acid adenine dinucleotide (NAADP) have been shown to mobilize Ca+2 via
      independent mechanisms. Although the structures of cADPR and NAADP are totally
      distinct, both nucleotides can be synthesized by ADP-ribosyl cyclase or CD38, a
      lymphocyte antigen. Both enzymes cyclize NAD to cADPR. In the presence of
      nicotinic acid the two enzymes catalyze a base exchange reaction resulting in the
      synthesis of NAADP from NADP. The switch between these two modes of catalysis is
      regulated by pH. Furthermore, both enzymes can also cyclize nicotinamide guanine
      dinucleotide (NGD) to produce a fluorescent product, cyclic GDP-ribose (cGDPR),
      which has a site of cyclization different from cADPR. A model is proposed to
      account for the multi-functionality of these enzymes. In order to be able to
      verify the model, a soluble ADP-ribosyl cyclase has been crystallized and X-ray
      diffraction shows that it is a dimer. Solution of the crystal structure of the
      cyclase should provide valuable insight into the structural features necessary
      for its multiple catalytic functions.

PMID- 9193684
TI  - Signal transduction via the CD38/NAD+ glycohydrolase.
AB  - The human cell surface CD38 molecule is a 46-kDa type-II transmembrane
      glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C
      terminal extracellular one. We previously demonstrated that an ecto-form NAD+
      glycohydrolase (NADase) activity induced by all-trans retinoic acid in HL-60
      cells is due to the extracellular domain of CD38. In the present study, we
      investigated a possible signal transduction mediated through CD38 in the retinoic
      acid-differentiated HL-60 cells with anti-CD38 monoclonal antibodies (mAbs). The
      addition of selected anti-CD38 mAbs to the cells induced rapid tyrosine
      phosphorylation of the cellular proteins with the molecular weights of 120,000,
      87,000 and 77,000; the phosphorylated 120-kDa protein was identified as the c-cbl
      proto-oncogene product, p120c-cbl. Furthermore, the phosphorylated p 120c-cbl
      associated with the 85-kDa subunit of phosphatidylinositol 3-kinase. To determine
      the relationship between the amino acid sequence responsible for the NADase
      activity and epitopes recognized by the stimulatory mAbs, we produced its carboxy
      terminal deletion mutants in COS-7 cells. The mutants with less than 15 amino
      acids deleted from the carboxyl terminus of the 300-amino acid wild-type molecule
      still maintained NADase activity, but those with more than 27 amino acids deleted
      did not. Introduction of site-directed mutation of a cysteine residue (Cys275),
      located in the 273-285 sequence, completely abolished the NADase activity. These
      CD38 mutants were also used for an epitope mapping of anti-CD38 mAbs. All the
      epitopes recognized by the mAbs inducing the tyrosine phosphorylation were mapped
      on the same Cys275-containing sequence of 273-285. Thus, the discrete carboxy
      terminal sequence not only plays a key role in its ecto-NADase activity, but also
      contains the epitopes of the agonistic anti-CD38 mAbs for the transmembrane
      signaling. We also found that the agonistic mAbs markedly potentiate superoxide
      generation induced by the stimulation of G protein-coupled chemotactic receptors.
      Our results suggested that the stimulation of CD38 might generate an accessory
      signal(s) to enhance the G protein-mediated signaling, probably though the
      protein-tyrosine phosphorylation.

PMID- 9193685
TI  - Ca(2+)-signalling in human T-lymphocytes. Potential roles for cyclic ADP-ribose
      and 2'-phospho-cyclic ADP-ribose.
AB  - Intracellular Ca(2+)-signals belong to the major events transducing extracellular
      signals into living cells. The discovery of (i) a caffeine-sensitive
      intracellular Ca(2+)-pool in Jurkat T-lymphocytes [1] and (ii) cyclic adenosine
      diphosphoribose (cADPR) as an agent that mobilizes Ca2+ from a caffeine- and
      ryanodine sensitive Ca(2+)-store in sea urchin egg homogenates [2] prompted us to
      investigate the potential role of this compound in T-lymphocyte Ca(2+)
      signalling. cADPR, as well as its 2'-phosphorylated derivative, 2'-phospho-cADPR
      (2'-cADPR), released Ca2+ in a dose-dependent, specific manner from
      intracellular, non-endoplasmic reticular stores of permeabilized Jurkat and HPB.
      ALL T cells. In addition, attempts were made to prove the presence of endogenous
      cADPR and 2'-P-cADPR by HPLC. Several HPLC protocols, including microbore-HPLC
      were tested resulting in the detection of endogenous cADPR by sequential
      separation on strong-anion exchange HPLC and reverse-phase ion-pair HPLC.

PMID- 9193686
TI  - Metabolism and actions of ADP-riboses in coronary arterial smooth muscle.
AB  - The present study examined the metabolism of ADP-ribose (ADPR) and cyclic ADP
      ribose (cADPR) in small bovine coronary arterial homogenates and characterized
      the effects of these nucleotides on the activity of potassium (K+) channels in
      coronary smooth muscle cells. ADPR and cADPR were produced from NAD+ (1mM) by
      homogenates from small bovine coronary arteries. The conversion rate was 2.81 +/-
      0.19 nmol/min/100 micrograms protein for ADPR and 1.37 +/- 0.03 nmol/min/100
      micrograms protein for cADPR. In patch clamp experiments, ADPR produced a
      concentration-dependent increase in the activity of a calcium activated K (Kca)
      channel in inside-out membrane patches of coronary arterial smooth muscle cells
      at concentrations of 0.1, 1 and 10 microM. The open state probability (NPo) of
      Kca channel was maximally increased 5-fold at a concentration of 10 microM. cADPR
      reduced the activity of Kca channel at concentrations of 1 and 10 microM. The NPo
      was decreased by 45% and 75%, respectively. The results indicate that there is an
      enzymatic pathway in the coronary arterial smooth muscle to produce ADPR and
      cADPR. These nucleotides may play a role in the control of coronary vascular tone
      by altering the activity of the Kca channel in vascular smooth muscle cells.

PMID- 9193687
TI  - Bovine liver mitochondrial NAD+ glycohydrolase. Relationship to ADP-ribosylation
      and calcium fluxes.
AB  - Mitochondrial NAD+ glycohydrolase (NADase) has been proposed to be required for
      (nonenzymatic) ADP-ribosylation and subsequent activation of a Ca2+ release
      pathway. In our studies it has been found that several agents including
      nicotinamide, dithiothreitol, and EDTA exert no or little effect on ADP
      ribosylation in isolated bovine liver mitochondria, while strongly inhibiting the
      NADase. The NADase did, however, catalyze the formation of cyclic purine
      nucleoside diphosphoriboses (similar to cyclic ADP-ribose) from NAD+ analogs. It
      appears possible, therefore, that this enzyme may be involved in the regulation
      of mitochondrial Ca2+ fluxes by forming a potent Ca(2+)-mobilizing agent, rather
      than by providing the substrate for non-enzymatic ADP-ribosylation.

PMID- 9193688
TI  - Characterization of hydrosoluble and detergent-solubilized forms of mitochondrial
      NAD+ glycohydrolase from bovine liver.
AB  - Treatment of isolated bovine liver mitochondria with either detergents or a crude
      pancreatic lipase, steapsin, resulted in solubilization of NAD+ glycohydrolase
      (NADase) activity. The two forms of this enzyme can be visualized directly in SDS
      polyacrylamide gels (PAGs) by a fluorescence assay utilizing 1,N6-etheno-NAD+
      (epsilon-NAD+) as substrate. Only a slight difference of about 2,000 in the
      apparent molecular masses was detected. Values of 28,000 and 30,000 for the
      steapsin- and detergent-solubilized enzyme, respectively, were estimated. The
      catalytic properties as well as the dependence on temperature, pH, and ionic
      strength were found to be similar for both forms of the enzyme. One important
      difference regarding their sensitivity against bivalent metal ions was observed.
      While the detergent-solubilized NADase was activated in the presence of, for
      example, Zn++, and inhibited by EDTA, the truncated enzyme seemed to be
      unaffected under these conditions.

PMID- 9193689
TI  - Contemplations on the evolution of pro- and eukaryotic mono(ADP-ribosyl)
      transferases in the context of the immune system.

PMID- 9193690
TI  - The vertebrate gene family of mono(ADP-ribosyl)transferases. Proposal for a
      unified nomenclature.

PMID- 9193691
TI  - The independent medical examiner.

PMID- 9193692
TI  - Chondrocyte transplantation and experimental treatment options for articular
      cartilage defects.
AB  - Current treatment options for injured articular cartilage have resulted in
      temporary improvements in clinical symptoms and functional levels. None of these
      modalities, however, has resulted in restoration of an articular surface that is
      able to withstand long-term joint loading and function. As a result, numerous
      investigators have attempted to devise alternative therapies. The limited
      regnerative potential of articular cartilage has led investigators to attempt
      using cells with the potential for differentiation and proliferation to repair
      chondral defects. Chondrocyte transplantation, both allogeneic and autogenous,
      has shown early promising results in regenrating hyaline-like tissue in both
      animals and humans. Encouraging results in animals have also been demonstrated
      with alternative sources of osteoprogenitor cells as grafts, as well as with
      natural/synthetic implants and the use of growth factors and cytokines. However,
      despite encouraging short-term results, long-term data concerning the regenerate
      tissue are still needed. As more research is being conducted to understand the
      processes of cartilage maintenance and healing, there is hope that cartilage
      regeneration and neochondrogenesis will be possible in the future.

PMID- 9193693
TI  - Design of the femoral component for cementless hip replacement: the surgeon's
      perspective.
AB  - Few guidelines are currently available to the surgeon when choosing a specific
      femoral component for cementless total hip replacement (THR). A survey of the
      members of the American Association for Hip and Knee Surgeons (AAHKS) was
      conducted to gain insight into the importance of implant material, stress
      shielding, and micromotion in the selection of cementless femoral components. A
      comprehensive survey was distributed to 300 orthopedic surgeons selected from the
      members of the AAHKS; 169 of the 300 surgeons completed the detailed
      questionnaire. The results of the survey were analyzed using the SPSS software
      package to obtain general trends in opinion, and a stepwise regression analysis
      was used to correlate responses with training and clinical experience.
      Interestingly, there was little consensus among surgeons with respect to the
      relative importance of implant material, stress shielding, and micromotion in the
      selection of prostheses for cementless THR. In general, bone loss secondary to
      stress shielding was the least important issue, and axial and rotational
      micromotion were considered progressively more significant problems. Cementless
      titanium alloy stems were perceived as offering no significant advantage over
      cobalt chrome alloy stems. Moreover, there was no consensus as to whether a
      collar was advantageous. Prosthesis stability, restoration of motion, and a
      proven clinical record were more important to surgeons than were ease of
      implantation and removal, cost, and availability.

PMID- 9193694
TI  - Fracture healing: role of NSAIDs.

PMID- 9193695
TI  - Colles' fracture: efficacy of pins and plaster.

PMID- 9193696
TI  - Anatomic considerations of anterior instrumentation of the thoracic spine.
AB  - Forty-seven dry thoracic specimens from T-3 to T-12 (470 thoracic vertebrae) were
      used to measure the dimensions of the vertebral body of the thoracic spine and to
      determine the relationship of the posterior angulation of screw placement to the
      spinal canal from different entrance points. Statistically significant
      differences in dimensions of male and female specimens were found in the anterior
      vertebral body height and all of the angular measurements. The average maximum
      posterior angle relative to the frontal plane from T-3 to T-12 for both sexes
      ranged from 11 degrees to 14 degrees at the initial point (the level of the most
      anterior edge of the upper costal facet), from 20 degrees to 23 degrees at the
      point of 5 mm anterior to the initial point, and from 30 degrees to 34 degrees at
      the point of 10 mm anterior to the initial point. This study suggests that there
      is considerable risk of violating the spinal canal if the screws are
      inadvertently angled posteriorly. The authors recommend insertion of screws in
      the anterior or middle part of the lateral aspect of the vertebral body. The
      screws should be directed perpendicular to the lateral plane of the vertebral
      body. A posteriorly placed screw should be directed anteriorly.

PMID- 9193697
TI  - Vascular calcification as a source of hand pain and weakness in a patient with
      end-stage renal failure.
AB  - This article describes a unique case of vascular calcification of the hands
      complicated by pain and weakness. The case demonstrates the interaction of the
      skeletal and renal systems and the consequences of an unrecognized imbalance of
      calcium and phosphorus metabolism. Definitive medical management to keep the
      calcium-phosphate product below 70 through the judicious use of aluminum
      phosphate binders and diet should be coordinated to prevent and limit the extent
      of these calcifications.

PMID- 9193698
TI  - Low-grade central osteosarcoma resembling fibrous dysplasia. A report of two
      cases.
AB  - We describe 2 cases of low-grade central osteosarcoma mimicking fibrous dysplasia
      and present a review of the literature. These cases illustrate the importance of
      obtaining a large representative sample of tumor in suspicious lesions, because
      it may be difficult or impossible to histologically distinguish low-grade central
      osteosarcoma from a benign lesion with limited samples from a core biopsy or
      needle aspiration. The treatment of choice for low-grade central osteosarcoma is
      resection with wide surgical margins or, if limb salvage is not technically
      feasible, amputation.

PMID- 9193699
TI  - Delayed union following stress fracture of the distal fibula secondary to
      rotational malunion of lateral malleolar fracture.
AB  - We present a case of delayed union following stress fracture of the distal fibula
      secondary to rotational malunion of a lateral malleolar fracture. The patient
      underwent operative excision of the nonunion, plating with autogenous iliac bone
      grafting, and correction of the malrotation of the distal fibular fragment. The
      fracture healed, and the patient was asymptomatic with full range of motion at
      follow-up. This report documents an unusual etiology, "external malrotation," for
      delayed union of a fibular stress fracture.

PMID- 9193700
TI  - Iliopsoas abscess following catheterization of the femoral artery: diagnostic and
      treatment strategies.
AB  - The following case is presented to illustrate the necessity of arthrotomy of the
      hip when an iliopsoas abscess lies adjacent to the hip joint capsule. Arthrotomy
      of the hip through a separate incision adds minimal morbidity, does not expose
      the hip to the abscess, and assures the surgeon that the hip has been debrided.
      This is important considering the 15% incidence of communication of the iliopsoas
      bursa with the hip joint.

PMID- 9193701
TI  - Chemistry, analysis, and biological roles of S-nitrosothiols.

PMID- 9193702
TI  - A method for biotin labeling of biologically active oligogalacturonides using a
      chemically stable hydrazide linkage.
AB  - Oligogalacturonides (oligomers of alpha-1,4-D-galacturonic acid) with degrees of
      polymerization (DP) between 8 and 16 were labeled with biotin using a rapid and
      simple two-reaction protocol that yields a stable oligogalacturonide derivative.
      In the first reaction biotin-x-hydrazide was coupled to the anomeric carbon of
      the reducing galacturonic acid residue by a hydrazone linkage. Carbohydrate
      hydrazone linkages such as these have been widely used to label a variety of
      biomolecules. However, we show herein that the oligogalacturonide-hydrazone
      linkage is hydrolyzed in water. In the second reaction the hydrazone linkage was
      reduced with sodium cyanoborohydride to form a stable hydrazide. The stability of
      hydrazide-linked oligogalacturonides was confirmed using high-performance anion
      exchange chromatography (HPAEC). The biotin and uronic acid content of the HPAEC
      fractions was determined using quantitative colorimetric microplate assays.
      Electrospray mass spectrometry and 1H NMR spectroscopy were used to confirm the
      structure of the HPAEC-purified biotin-derivatized oligogalacturonides. Biotin
      derivatized oligogalacturonides will be useful in studies of the biological
      functions of oligogalacturonides.

PMID- 9193703
TI  - Solid-phase extraction in malondialdehyde analysis.
AB  - Malondialdehyde (MDA) has been widely used as an index of lipoperoxidation in
      biological and medical sciences as well as in the food industry. A solid-phase
      extraction (SPE) of the condensation product of the MDA with 2-thiobarbituric
      acid (TBA) was developed using LiChrolut C18ec, 200 mg (Merck, Darmstadt,
      Germany), as a SPE cartridge and methanol as an eluent for sample pretreatment
      before HPLC analysis. The samples of blood plasma, platelet concentrates, or
      erythrocyte membranes (ghosts) were deproteinized by acetonitrile in the presence
      of sodium hydroxide prior to the reaction with TBA. The reaction mixture was
      processed using SPE. The SPE extracts (800 microL of methanol) were put to
      dryness and after dissolution with 100 microliters of mobile phase, 50
      microliters was analyzed by RP-HPLC with fluorescence detection (excitation at
      514 nm, emission at 556 nm). The mean MDA concentration in plasmas of 32 healthy
      donors was 0.37 +/- 0.25 mumol/L and the mean MDA concentration in normal ghosts
      was 8.3 +/- 4.1 pmol/microgram of protein content. In the case of a patient with
      a severe form of beta-thalassemia, the concentration of plasma MDA was raised to
      1.22 mumol/L and the amount of MDA in erythrocytal ghosts was raised to 21.05
      pmol/microgram of protein content. MDA concentration in platelet concentrates
      (six bags) in the first day of storage was 0.46 +/- 0.18 mumol/L and in the fifth
      day of storage was 0.55 +/- 0.44 mumol/L.

PMID- 9193704
TI  - Zymography: a single-step staining method for quantitation of proteolytic
      activity on substrate gels.
AB  - Zymography is an electrophoretic method for measuring proteolytic activity. The
      method is based on an sodium dodecyl sulfate gel impregnated with a protein
      substrate which is degraded by the proteases resolved during the incubation
      period. Coomassie blue staining of the gel reveals sites of proteolysis as white
      bands on a dark blue background. Within a certain range the band intensity can be
      related linearly to the amount of protease loaded. Although the method is widely
      used, crucial points concerning quantitation of proteolytic activity have not
      been rigorously addressed. In this report we describe a new staining protocol
      which converts the independent staining and destaining procedure into a single
      step. This leads to fast and reproducible staining of zymograms permitting
      reliable quantitation of proteolytic activity. As shown for proMMP-9 (type IV
      gelatinase-b) proteolytic activity can be quantitated in a linear manner in as
      little as 1 h of zymogram staining. We established the detection limit for proMMP
      9 (32 pg), the linear range (below 1000 pg), and the reproducibility of the assay
      (coefficient of variation < 15%). This improved protocol is fast and
      reproducible. Its linear range of almost two log scales permits assay of
      proteolytic activity in a wider range than current methods.

PMID- 9193705
TI  - A high-throughput STAT binding assay using fluorescence polarization.
AB  - STAT (signal transducers and activators of transcription) is a class of
      transcription factors that are activated upon cytokine or growth factor binding
      to cell surface receptors. Activated STAT proteins dimerize, translocate into the
      nucleus, and activate transcription, leading to various immune responses. The
      inhibition of STAT binding to cell receptors might provide a means to modulate
      these immune responses. We developed a high-throughput biochemical assay to
      measure the interaction between an interferon-gamma receptor-derived
      phosphotyrosine-containing peptide and STAT1, using fluorescence polarization as
      the detection method. This assay can be used to screen for small molecules
      capable of disrupting receptor-STAT interactions.

PMID- 9193706
TI  - Coelenterazine analogs as chemiluminescent probe for superoxide anion.
AB  - Eleven new coelenterazine analogs containing the 3,7-dihydroimidazo[1,2
      alpha]pyrazin-3-one structure were synthesized. The superoxide-triggered
      chemiluminescence of these compounds was investigated using the hypoxanthine
      xanthine oxidase system in comparison with four known compounds. The results
      showed that an alkyl substitution at the position 5 of the imidazopyrazinone ring
      causes a drastic decrease in the superoxide-dependent chemiluminescence
      intensity, whereas a dimethylene bridge added between the position 5 and the
      phenyl group bound to the position 6 dramatically increases the luminescence
      intensity, indicating the potential usefulness of this type of compound as a
      probe for superoxide anion. The luminescence intensity of the bridged analog was
      33 times greater than that of MCLA [2-methyl-6-(4-methoxyphenyl)-3, 7
      dihydroimidazo[1,2-alpha]pyrazin-3-one], the most sensitive superoxide probe of
      Cypridina luciferin-type. Two of the analogs synthesized, each with a covalently
      bound cyclodextrin, had a good solubility in water, an advantage in actual use.
      Moreover, one of them having a beta-cyclodextrin group showed a unique property;
      its luminescence was little affected by various substances in the environment.

PMID- 9193707
TI  - Direct visualization of individual DNA molecules by fluorescence microscopy:
      characterization of the factors affecting signal/background and optimization of
      imaging conditions using YOYO.
AB  - A new series of high-affinity cyanine dyes was tested for the visualization of
      the dynamics of single DNA molecules through a fluorescence microscope. In
      particular, YOYO-1 (1,1'-(4,4,7,7-tetramethyl-4,7-diazaundecamethylene)- bis-4-[3
      methyl-2,3-dihydro-(benzo-1,3-oxazole)- 2-methylidene]-quinolinium tetraiodide)
      forms a very stable, highly fluorescent complex with double-stranded DNA and
      dramatically improves the quality of the images. We have characterized the
      factors affecting the signal/background in the imaging of single DNA molecules by
      fluorescence microscopy and compared the results obtained using YOYO-1 with those
      obtained using standard fluorescent dyes like ethidium bromide or acridine
      orange.

PMID- 9193710
TI  - Successive isolation and separation of the major lipid fractions including
      gangliosides from single biological samples.
AB  - Currently available techniques concerning extraction and characterization of the
      different lipids from biological specimens are designed for particular families
      and do not address consecutive isolation of lipid constituents in their
      globality. We describe here a simple, nondestructive chromatographic procedure
      that allows efficient elution and further analysis of the major lipid classes
      (neutral lipids, phospholipids, nonsialylated sphingolipids, and gangliosides) in
      their natural states from the same starting material. The procedure describes the
      use of solvent mixtures adapted to silicic acid column chromatography and permits
      90-97% recovery of each of the above lipid groups. We have particularly
      concentrated on optimizing the efficient recovery of the diverse minor forms of
      gangliosides, free of other contaminants, from relatively small amounts of neural
      tissue. As model systems we have used in vivo and in vitro preparations of
      mammalian retina for which only fragmentary data are available on lipid
      composition. We show that relative to brain, retina contains, for example,
      twofold more sphingomyelin and sixfold more GD3 ganglioside. In turn, cultured
      retinal glial cells contain twofold higher levels of globoside and eightfold
      higher amounts of GM3 ganglioside with respect to intact retina. Compared to
      previously published techniques, we obtain improved total ganglioside recovery,
      with enrichment of poly-sialogangliosides. The technique presented here should be
      widely applicable to analyze global lipid composition of diverse biological
      samples.

PMID- 9193708
TI  - A fluorescent substrate of transglutaminase for detection and characterization of
      glutamine acceptor compounds.
AB  - A fluorescent dipeptide was designed to discover glutamine acceptor proteins of
      transglutaminase. Starting materials for synthesis were the commercially
      available compounds carbobenzoxy-L-glutaminylglycine (CBZ-Gln-Gly) and
      monodansylcadaverine (C-DNS) which were coupled to obtain CBZ-Gln-Gly-C-DNS 1 [1
      N-(carbobenzoxy-L-glutaminylglycyl)-5-N- (5'-N', N'-dimethylamino-1'
      naphthalenesulfonyl)- diamidopentane]. The glutamine peptide is a substrate of
      bacterial transglutaminase from Streptoverticillium mobaraense as well as of the
      guinea pig liver enzyme. This could be shown by incorporating 1 into alpha s1
      casein resulting in a significant increase in fluorescence intensity and a
      concomitant inhibition of cross-linking reaction. Additionally, dipeptide 1 is a
      useful tool to characterize the specificity of transglutaminase toward small
      primary amines. We established a sensitive HPLC assay and determined the kinetic
      parameters of several alkylamines. Hydrolysis of 1 is suppressed in the presence
      of the nucleophiles as it could be demonstrated with different concentrations of
      butylamine in semiquantitative studies. Together with labeled primary amines,
      reagent 1 seems to be a particularly suitable tool for examining acceptor-donor
      relationships of transglutaminase substrates.

PMID- 9193709
TI  - Fluorometric detection of biological S-nitrosothiols.
AB  - A technique is presented for the quantitative detection of S-nitrosothiols formed
      by model biological thiols, cysteine, glutathione, and serum albumin. The
      technique is based on the detection of fluorescent compound 1-[H]-naphthotriazole
      formed between 2,3-diaminonaphthalene and nitrous acid released from S
      nitrosothiols by treatment with mercuric chloride in an acidic environment.
      Concentration of S-nitrosothiols is determined from the difference in fluorescent
      signal (excitation/emission wavelengths of 363 nm/450 nm, respectively) observed
      in the presence and absence of 0.18 mM HgCl2. The yield of the reaction between
      2,3-diaminonaphthalene and nitrous acid released from the S-NO bond by HgCl2
      approaches 90-100% as documented by simultaneous assays of S-nitrosothiols by uv
      spectrophotometry and by Saville method. The assay can be applied to the analysis
      of mixtures containing excess of thiol and/or nitrite at neutral pH by
      pretreatment of samples with N-ethylmaleinimide and/or ammonium sulfamate,
      respectively. In analysis of S-nitrosothiols in protein-containing mixtures,
      HgCl2-mediated release of nitrous acid in the presence of 2,3-diaminonaphthalene
      is followed by neutralization of samples and precipitation of protein with 0.5 M
      5-sulfosalicylic acid. The fluorometric assay is carried out at an excitation
      wavelength of 380 nm to eliminate the background fluorescence of 5-sulfosalicylic
      acid observed at lower wavelengths. The technique offers simple and rapid
      determination of S-nitrosothiols in complex reaction mixtures with the detection
      limit at low nanomolar concentrations.

PMID- 9193711
TI  - Separation of 18 6-aminoquinolyl-carbamyl-amino acids by ion-pair chromatography.
AB  - Eighteen 6-aminoquinolyl-carbamyl (AQC)-amino acids were separated by ion-pair
      chromatography, using tetrabutylammonium (TBA) as a counterion. Optimum
      separation was obtained on a C8 reverse-phase column using gradient elution with
      two mobile phases, A (5 mM TBA, 75 mM ammonium acetate, pH 7.5) and B (80%
      acetonitrile). The AQC-amino acids were detected by fluorescence with excitation
      at 250 nm and emission at 395 nm, and the analysis time was 65 min. The response
      factors of individual AQC-amino acids to AQC-phenylalanine ranged from 0.42 to
      1.08 (except for tryptophan at 0.01), with an average of 0.8. Detection limits by
      fluorescence ranged from 11.8 fmol (threonine) to 51.7 fmol (methionine), except
      for tryptophan (1.8 pmol).

PMID- 9193712
TI  - Characterization of antibody 444 using chromatographically purified enantiomers
      of juvenile hormones I, II, and III: implications for radioimmunoassays.
AB  - Optically pure (> 99.5%) enantiomers of insect juvenile hormones (JH) I, II, and
      III were obtained by injection of racemic mixtures onto a chiral HPLC column
      using hexane:2-propanol (99.5:0.5) as the mobile phase. The enantiomers of JH III
      were the best resolved (R = 4.26), followed by those of JH II (R = 2.29) and JH I
      (R = 1.47). These purified natural and unnatural enantiomers were used to further
      characterize an antiserum (444) developed for JH radioimmunoassays (RIAs). Based
      on ED50 values generated using optically pure [methyl-3H]-10R,11S-JH II as a
      tracer, the natural isomers of JH I, JH II, and JH III were 30, 87, and 36 times
      more immunoreactive, respectively, than the unnatural isomers. When compared with
      the racemates, the natural isomers were approximately twice as immunoreactive. In
      competitive displacement studies where the natural enantiomers of the three JHs
      were compared, immunoreactivities were in the order JH II > JH I > JH III (ED50 =
      109, 198, and 300, respectively). Availability of pure natural enantiomers of JH,
      both as tracers and competitors, should improve the sensitivity and accuracy of
      JH titer determinations made by RIA and facilitate various enzyme, binding
      protein, and receptor studies.

PMID- 9193713
TI  - A microtiter-based fluorescence assay for (1,3)-beta-glucan synthases.
AB  - A high-throughput assay for UDP-Glc:(1,3)-beta-glucan synthase(EC 2.4.1.34, UDP
      glucose:1,3-beta-D-glucan, 3-beta-glucosyltransferase) from fungi and higher
      plants is described. The assay is performed in microtiter plates and is extremely
      inexpensive compared to other standard assays for these enzymes. The reduction in
      price is achieved by replacing the conventional substrate UDP-[14C]Glc with its
      nonradioactive counterpart, and the nonradioactive glucan produced is quantified
      as a fluorescent complex following specific interaction with the fluorochrome
      present in commercial aniline blue. In addition to a > 100-fold reduction in
      cost, the assay is highly reproducible and nearly as sensitive as radioactive
      assays and has the additional advantages of increased safety and avoidance of the
      need for filtration and washing steps to collect the glucan product. As such, the
      assay is highly suitable for high-throughput screening for inhibitors of these
      enzymes.

PMID- 9193714
TI  - Label-free monitoring of DNA-ligand interactions.
AB  - We report on the label- and isotope-free monitoring of DNA interactions with low
      molecular-weight ligands. An optical technique based on interference at thin
      layers was used to monitor in real time binding of ligands at DNA which was
      immobilized by Coulomb interactions at a positively charged surface.
      Approximately 2 ng DNA/m2 was irreversibly bound to the surface, which remained
      stable over several days. This result was confirmed by characterization of the
      layer using spectroscopic ellipsometry. During incubation of immobilized DNA with
      a variety of intercalators and other DNA-binding compounds in a flow system,
      interactions were monitored by reflectometric interference spectroscopy. Binding
      effects between 10 and 400 pg/ mm2 were detected unambiguously. Nonspecific
      binding effects were excluded by using a negatively charged reference surface.
      Variation of intercalator concentration allowed the characterization of
      interaction with respect to kinetics and thermodynamics by the evaluation of
      binding rate and equilibrium coverage. The affinity constants were determined in
      the range between 10(5) and 10(6) M-1, in good agreement to those obtained by
      homogeneous phase assays. Association rate constants between 10(3) and 10(5) M-1
      s-1 and dissociation rate constants between 10(-1) and 10(-2) s-1 were determined
      by evaluation of the binding curves. Both the fast and simple test format and a
      universal applicability make the new technique described attractive for detecting
      and characterizing interaction of low-molecular-weight molecules with DNA.

PMID- 9193715
TI  - Differential effect of Nonidet P40 on DNA binding of transcription factors.

PMID- 9193716
TI  - Fast sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of
      protein fractions.

PMID- 9193717
TI  - Purification of the death substrate poly(ADP-ribose) polymerase.

PMID- 9193719
TI  - Determination of cysteine residues in protein sequence analysis at the picomole
      level.

PMID- 9193718
TI  - A radioactive assay for sialyltransferase activity using 96-well multiscreen
      filtration plates.

PMID- 9193720
TI  - A general method for single-stranded DNA probe generation.

PMID- 9193721
TI  - Urease assay using a rapid radiometric procedure.

PMID- 9193722
TI  - Retinoid binding proteins in mouse yolk sac and chorio-allantoic placentas.
AB  - In the adult, as well as in the embryo, a number of specific extra- and
      intracellular binding proteins such as the plasma retinol binding protein (RBP),
      the cellular retinol binding protein type I (CRBP I), and also the cellular
      receptors for RBP are thought to regulate transport and metabolism of retinol
      (vitamin A). Since the regulation of materno-fetal transport of vitamin A is not
      well understood, we examined the localization of these proteins during the
      development of the mouse chorio-allantoic and yolk sac placentas. The
      labyrinthine region of the chorio-allantoic placenta, where exchange of
      substances can occur between the maternal and fetal circulations, did not contain
      RBP (mRNA or protein) or antigen(s) similar to the bovine RBP-receptor p63,
      whereas the visceral endoderm of the yolk sac placenta, the second site for
      materno-fetal transport, did. Furthermore, only the endodermal cells of the
      visceral yolk sac appeared to strongly accumulate radiolabelled retinoids. The
      cellular retinol binding protein (CRBP I) was detected both in the trophoblast
      layer of the placental labyrinth closest to the fetal endothelium (layer III),
      and in the visceral endoderm of the yolk sac. Together, these findings suggest
      that the yolk sac placenta mediates retinol transfer to the embryo/fetus
      throughout the entire gestation. The chorio-allantoic placenta, on the other
      hand, does not appear to have this capacity, while the presence of CRBP I does
      suggest a retinol-metabolizing capability.

PMID- 9193723
TI  - Confocal microscopy of cementocytes and their lacunae and canaliculi in rat
      molars.
AB  - The present study was designed to analyze the morphological characteristics of
      cementocytes and osteocytes. The maxillae of 10-week-old Wistar rats were used
      for observations. Non-decalcified ground sections stained vitally with
      fluorescence dyes and decalcified frozen sections stained with FITC-phalloidin
      were examined by confocal microscopy. Calcein and alizarin red stained the
      calcification front of bone, cementum, and dentin intensely. In addition, lacunae
      and canaliculi of cementocytes and osteocytes as well as dentinal canals were
      stained with the fluorescent dyes. The staining of lacunae and canaliculi was
      less intense than that of the calcification front of bone, cementum and dentin.
      The canaliculi of cementocytes and osteocytes were connected with the canaliculi
      extending from the calcification front of cementum and bone, respectively. The
      canalicular density was less in the cellular cementum than in the bone. Areas
      devoid of canaliculi were numerous in the cellular cementum, whereas areas devoid
      of canaliculi were scarce in the alveolar bone. Further, the lacunae of
      cementocytes showed various shapes, from oval to tubular, while the lacunae of
      osteocytes were invariably oval. The cell body and the cytoplasmic processes of
      cementocytes were positive for FITC-phalloidin within the extracellular matrix of
      cellular cementum, which was negative. The distribution of actin filaments in the
      osteocytes and the cementocytes was predominantly cortical and appeared to be
      closely associated with the cell membrane of the cell bodies and the cytoplasmic
      processes. Intense staining was seen at the proximal part of the cytoplasmic
      processes in both osteocytes and cementocytes, showing a punctuated structure of
      the cells that was more frequent in osteocytes than in cementocytes. The stress
      fiber known to be present in most of the cultured cells was not evident in the
      these cells in situ. The cells incorporated in the cementodentinal junction were
      strongly stained with FITC-phalloidin. The distribution pattern of the
      cytoplasmic processes stained with FITC-phalloidin was similar to that of the
      canaliculli stained vitally. The cytoplasmic processes of osteocytes and
      cementocytes were connected with those of cells lining the surface of bone and
      cementum. The present result-that lacunae and canaliculi of cementocytes were
      stained vitally with the fluorescence dyes-suggests that cementocytes may have a
      role in secondary calcification of cellular cementum. Further, the lower density
      of cytoplasmic processes in cementocytes than in osteocytes suggests a lack of
      complexity in the intercellular network within the cellular cementum.

PMID- 9193724
TI  - A duplicated Meckel's cartilage in a human fetus.
AB  - An exceptional case of a duplicate Meckel's cartilage in a human fetus, with a C
      R length of 57 mm, is studied. Another small cartilage, isolated from Meckel's,
      of rounded morphology, was observed in a small region between the
      temporomandibular joint and the middle ear. This cartilage was only present on
      the right side.

PMID- 9193725
TI  - Embryonic and postnatal development of the rat renal interstitium.
AB  - Whilst antihypertensive, structural and functional roles have been proposed for
      the cells of the renomedullary interstitium in the adult kidney, little is known
      about its role in renal development. Rat kidneys were studied throughout
      development, prenatally at gestational ages E14-E21 and postnatally at 0-28 days,
      by light microscopy, transmission and scanning electron microscopy and following
      immunocytochemistry. Renomedullary interstitial cells were observed as early as
      embryonic day E14, forming a loose, orderly network around branches of the
      ureteric bud. Paralleling the development of the first nephron structures,
      renomedullary interstitial cells were arranged in a concentric circular manner
      around collecting ducts. Following tubular and vascular growth from the cortex
      into the medulla, this arrangement resulted in the characteristic 'rungs of a
      ladder' appearance of interstitial cells between tubules, blood vessels and the
      collecting ducts. Renomedullary interstitial cells were closely adherent to
      basement membranes of tubules, blood vessels and collecting ducts from early in
      development. Contacts were absent between renomedullary interstitial cells and
      tubular structures in the process of remodelling, such as the hair-pin bends of
      the loops of Henle. At these foci laminin, a basement membrane glycoprotein was
      specificially localised to intracellular epithelial sites, whereas in more
      developed areas, laminin was restricted to epithelial basement membranes.
      Associated with the more mature structures, laminin was also localised to
      intracellular granules of renomedullary interstitial cells. Thus, renomedullary
      interstitial cells are present prior to and appear to be actively associated with
      tubule repositioning in the medulla, establishing themselves as integral to the
      process of renal development.

PMID- 9193726
TI  - Developmental expression of neuronal and endocrine markers in the parathyroid
      glands of the rat.
AB  - The parathyroid glands of the adult rat harbor a number of neuroendocrine
      markers, biologically active peptides and "classical" neuromessengers in addition
      to parathyroid hormone (PTH). Their appearance during parathyroid development is,
      however, not known. In the present study we have examined several neuroendocrine
      markers and neuromessengers in the parathyroid glands of the developing rat
      [embryonic stage 21(E21), newborn, 1, 2, 3, 4 week old, and adult rats] using
      immunocytochemistry. Chromogranin A- and PTH-mRNA were also examined by in situ
      hybridization and the mRNA levels were quantitated by computerized image
      analysis. Protein gene product 9.5- and synaptophysin-containing nerve fibers
      appeared already before birth and then gradually increased in number postnatally,
      and at the age of 4 weeks the nerve fibers were moderate in number to numerous.
      Nerve fibers containing calcitonin gene-related peptide, neuropeptide Y and
      vasoactive intestinal polypeptide also increased gradually in number, while
      galanin-, substance P- and tyrosine hydroxylase-containing fibers remained few
      throughout development. The glandular cells expressed chromogranin A,
      pancreastatin and PTH already before birth. The levels of chromogranin A- and PTH
      mRNA were low at E21 and increased markedly at birth; chromogranin A mRNA levels
      had increased even more at 1 week postnatally. Three to 4 weeks after birth the
      levels of PTH- and chromogranin A mRNA again increased, then stabilized at a
      slightly lower level in the adult rat. Our findings demonstrate that the
      parathyroid glands of rat are already innervated and express PTH and chromogranin
      A before birth and that the density of peptide-containing nerve fibers changes
      during development. The stepwise increases of PTH- and chromogranin A mRNAs
      during development indicate marked changes in parathyroid activity occurring at
      birth and at weaning.

PMID- 9193727
TI  - Quantitative examination of calcitonin gene-related peptide immunoreactive nerve
      fibres in the cat knee joint capsule.
AB  - The knee joint of the cat has been used extensively to study the morphology and
      function of primary afferents in a deep somatic tissue. A proportion of these
      neurones synthesizes various neuropeptides, with calcitonin gene-related peptide
      being the most prominent. In the present study we examined the distribution and
      density of nerve fibers immunoreactive for calcitonin gene-related peptide within
      the medial articular capsule. The fibres were predominantly located in the
      superficial layer of the capsule. They formed a dense innervation pattern, mainly
      accompanying blood vessels. Electron microscopy showed that most fibres were in
      close proximity to small arteries. The highest innervation density was found in
      parts of the capsule that were located over the epicondyle of the femur with 21
      +/- 12 fibres per mm2 (mean +/- SD). In the tissue over the joint cleft this
      density was lower, with 11 +/- 6 fibres per mm2. In conclusion, the high
      innervation density of the knee joint capsule by nerve fibres containing
      calcitonin gene-related peptide supports the hypothesis of an important
      regulatory function of this peptide in normal tissue.

PMID- 9193728
TI  - The developmental skeletal growth in the rat foot is reduced after denervation.
AB  - It has long been known that bone is innervated. In recent years it has been
      suggested that the local nerves may influence the growth and metabolism of bone
      by way of neuropeptides. The transient local presence of nerve-containing
      cartilage canals just before formation of secondary ossification centres in rat
      knee epiphyses seems to support that view. The purpose of the present study was
      to see if denervation affects the developmental growth of metatarsal bones in the
      rat hindfoot. We made sciatic and femoral neurectomies in 7-day-old rat pups and
      examined the hindfeet at various times after surgery. Immunohistochemical
      analysis showed that denervation was complete. Radiographic examination revealed
      that the metatarsal bones were significantly shorter in denervated hindfeet 30
      days after denervation (average relative shortening 9.9 +/- 2.3%). Measurements
      of total foot length showed that denervated feet were subnormally sized already
      five days postoperatively, before the onset of secondary ossification. The timing
      of the latter was not affected by denervation. Control rats subjected to
      tenotomies exhibited normal metatarsal bone lengths. On the basis of these
      results we suggest that the local nerves may influence the growth of immature
      bones but do not affect secondary ossification.

PMID- 9193729
TI  - Development of the retinotectal system in the pigeon: a cytoarchitectonic and
      tracing study with cholera toxin.
AB  - The optic tectum of the pigeon (Columba livia) is marked by morphological dorso
      ventral and left-right differences. Both features seem to be related to
      functional specializations, but the responsible developmental mechanisms are
      unclear. Since the visual system becomes functional only after hatching, the
      developmental processes might be extended into the post-hatching period. The
      development of the asymmetries in the tectofugal system, however, depends on an
      asymmetric light stimulation acting already before hatching. As a first attempt
      to resolve this discrepancy, we examined the ontogeny of the retinotectal system
      by labeling the developing retinal projection with cholera toxin subunit B, in
      conjunction with an analysis of the cytoarchitectonic differentiation of the
      optic tectum. The data demonstrate that the first fibers to penetrate all
      retinoreceptive tectal layers could be observed from embryonic day 15 onwards,
      indicating that visual information could in principle be already processed before
      hatching. The afferent projection already exhibited the adult lamination pattern
      directly at the beginning of the invasion of the tectal layers; a surprising
      finding, since at that time the lamination pattern of the tectal layers did not
      have an adult appearance. The differentiation of the outer retinoreceptive
      laminae started only when the whole optic tectum was occupied by retinal fibers,
      4 days after hatching, and was finished a week later. The dorso-ventral
      differences in the thickness of layers 4 and 5 were not apparent before the first
      week after hatching. The late appearance of these differences indicates that
      their maturation may be influenced by retinal input.

PMID- 9193730
TI  - Changes in otoacoustic emissions in patients with idiopathic sudden deafness.
AB  - Transiently click-evoked (TEOAE), distortion product (DPOAE) and spontaneous
      otoacoustic emissions (SOAE) were recorded and changes in these tests were
      studied during the recovery process in 15 cases of idiopathic sudden deafness
      (ISD). In all these cases the amplitudes of TEOAEs and DPOAEs increased
      concurrently with the recovery of the hearing threshold. Ears with ISD were not
      different in their OAE characteristics from ears with other forms of
      sensorineural hearing loss (SNHL). In 4 of the 15 cases, SOAEs could be detected
      when hearing had recovered. These results suggest that the function of outer hair
      cells (OHCs) had deteriorated when the hearing threshold was elevated and that
      OHC activity recovered as hearing improved to nearly normal levels in ISD cases
      with good outcome.

PMID- 9193731
TI  - Middle ear mechanics in subjects with rheumatoid arthritis.
AB  - The incudo-malleolar and incudo-stapedial joints are true diarthroses and
      therefore may be subject to the same rheumatic lesions as any other articulation
      in the body. The existence of this involvement in rheumatoid arthritis (RA),
      however, is highly controversial. The present study investigates modifications of
      the mechanical properties of the middle ear in a group of subjects with RA by
      evaluating the resonance frequency obtained with multiple-frequency tympanometry
      (MFT). Thirty patients with RA, aged 20 to 68 years (mean age: 45.8 +/- 12.4
      years), participated in the investigation. Their data were compared with those
      obtained in a control group of 48 age-matched subjects. Results obtained in both
      ears were examined in all subjects. The two groups displayed almost equal hearing
      levels with mean air conduction thresholds ranging from 10 to 22 dB HL. None of
      the subjects displayed an air-bone gap greater than 5 dB. Normal resonance
      frequency, calculated at the 95th percentile from the control group, ranged from
      900 to 1250 Hz. Twelve rheumatoid arthritis patients (40 per cent) displayed
      abnormal resonance values. These findings were monolateral in 9 patients and
      bilateral in 3. Eleven out of 15 ears with abnormal multiple-frequency
      tympanometry data were characterized by an increase in resonance and 4 by a
      decrease. A correlation between abnormal resonance values and more aggressive RA
      was established. The results of this study suggest that rheumatoid arthritis may
      involve the incudo-malleolar and incudo-stapedial joints, altering the ossicular
      mechanics in response to static air pressure modifications. This does not impair
      sound conduction through the middle ear, but might reduce the protective
      mechanisms of the middle ear towards high static pressures.

PMID- 9193732
TI  - Electrocochleographic analysis of the suppression of tinnitus by electrical
      promontory stimulation.
AB  - To investigate the origin, and evaluate the mechanism by which tinnitus is
      suppressed we performed electrical promontory stimulation (EPS) in 56 patients
      with tinnitus, and measured the compound action potential (CAP) using
      electrocochleography before and after EPS. In the group of patients in whom
      tinnitus was suppressed, the CAP amplitudes increased significantly, whereas the
      latencies showed no remarkable change. In the group of patients in whom tinnitus
      was not suppressed, both the CAP amplitudes and latencies exhibited no
      significant change. These data indicate that the effect on the cochlear nerve
      plays an important role in the suppression of tinnitus by EPS. The CAP reflects
      the number of the auditory nerve fibers which discharge synchronously. It is
      speculated that an increase of the CAP amplitudes is caused by synchronizing
      discharges of the auditory nerve fibers, and that the mechanism by which EPS
      suppresses tinnitus may be related to synchronizing these discharges.

PMID- 9193733
TI  - Assessing aspects of auditory handicap by means of pupil dilatation.
AB  - The demand on extra effort and concentration during listening are notorious
      handicapping effects of hearing impairment as is shown by self-assessment
      studies. In an attempt to explore new ways of assessing hearing handicap, the
      present study focuses on an objective measure of mental effort during listening.
      Pupil dilatation is used as the index of mental effort. Results for 14 hearing
      impaired and 14 normal hearing listeners show a relation between pupil dilatation
      and difficulty in speech reception in noise, as manipulated by the speech-to
      noise ratio. In addition the study shows that, with regard to effort and
      concentration, hearing-impaired subjects benefit less than normals from easier
      listening situations (e.g. at 5 dB above the individual speech-reception
      threshold). The results show a significant correlation between self-rated
      handicap and pupil dilatation.

PMID- 9193734
TI  - Audio-visual perception of compressed speech by profoundly hearing-impaired
      subjects.
AB  - For many people with profound hearing loss conventional hearing aids give only
      little support in speechreading. This study aims at optimizing the presentation
      of speech signals in the severely reduced dynamic range of the profoundly hearing
      impaired by means of multichannel compression and multichannel amplification. The
      speech signal in each of six 1-octave channels (125-4000 Hz) was compressed
      instantaneously, using compression ratios of 1, 2, 3, or 5, and a compression
      threshold of 35 dB below peak level. A total of eight conditions were composed in
      which the compression ratio varied per channel. Sentences were presented audio
      visually to 16 profoundly hearing-impaired subjects and syllable intelligibility
      was measured. Results show that all auditory signals are valuable supplements to
      speechreading. No clear overall preference is found for any of the compression
      conditions, but relatively high compression ratios (> 3-5) have a significantly
      detrimental effect. Inspection of the individual results reveals that compression
      may be beneficial for one subject.

PMID- 9193735
TI  - Increased levels of the nicotine metabolite cotinine in schizophrenic smokers
      compared to other smokers.
AB  - The purpose of this study was to determine if schizophrenic patients self
      administer more nicotine during cigarette smoking than nonschizophrenic subjects.
      Urinary cotinine, a nicotine metabolite, was measured in 20 schizophrenic
      patients and 20 nonschizophrenic subjects with similar smoking history.
      Schizophrenic patients had significantly higher urinary cotinine levels,
      suggesting that schizophrenics consume higher doses of nicotine, probably by
      deeper inhalation of cigarettes. Schizophrenic patients' higher dose of nicotine
      may target different receptors than those activated by the lower doses self
      administered by most nonschizophrenic smokers. In particular, high doses may
      activate low-affinity alpha-7 nicotinic receptors, associated with deficits in
      sensory inhibition in schizophrenia.

PMID- 9193736
TI  - Heterogeneity of serotonergic response in treatment-refractory schizophrenia
      patients.
AB  - Oral metachlorophenylpiperazine (m-CPP) as a direct-acting postsynaptic
      serotonergic agonist was used to study serotonergic dysfunction in treatment
      refractory chronic schizophrenia based on the hypothesis that some patients may
      show central serotonergic hypersensitivity. Seventeen DSM-III-R chronic
      schizophrenic patients with a history of neuroleptic nonresponse underwent double
      blind challenge with oral m-CPP (0.25 mg/kg body weight) and placebo after
      medication washout: m-CPP significantly elevated both prolactin and cortisol
      levels as compared to placebo. There was a significant relationship between
      change in cortisol level and change in psychopathology under m-CPP; a blunted
      cortisol response was associated with a decrease in total psychopathology, while
      an increase in cortisol response related to an increase in psychopathology.
      Similarly, decrease in severity of the activation factor and the hostility factor
      was associated with a smaller cortisol response in the m-CPP condition. These
      results point to heterogeneity in central serotonergic sensitivity within the
      context of different subpopulations of serotonergic receptors.

PMID- 9193737
TI  - N400 abnormalities in late life schizophrenia and related psychoses.
AB  - The N400, an event-related brain potential (ERP) sensitive to semantic congruity,
      has been reported to have increased latency and/or reduced amplitude in young
      adults with schizophrenia. Little is known, however, regarding the N400 in older
      schizophrenia patients, especially those with late onset. We studied 18 middle
      aged and elderly patients with schizophrenia and related psychoses (nine with
      early-onset psychosis (EOP) and nine with late-onset psychosis (LOP)), and nine
      normal comparison (NC) subjects. Subjects read words which were semantically
      incongruent (50%) or congruent (50%) with a preceding spoken phrase which defined
      either an antonymic or categorical relationship. The LOP group had a
      significantly later peak latency of the N400 congruity effect compared to the NC
      group. Seven of 18 psychosis patients, but none (0/9) of the normal subjects, had
      an abnormal latency or amplitude (p = 0.04), measured at T6 (right temporal).
      Smaller amplitudes were associated with more severe negative symptoms (rp = 0.58;
      p = 0.01). N400 abnormalities in older schizophrenia patients likely reflect
      abnormal processing of semantic information.

PMID- 9193738
TI  - Growth hormone response to sumatriptan (5-HT1D agonist) challenge in seasonal
      affective disorder: effects of light therapy.
AB  - To explore the role of serotonergic system in seasonal affective disorder (SAD),
      we compared growth hormone (GH) responses to a challenge with a novel 5-HT1D
      receptor agonist sumatriptan between 11 patients with SAD and nine healthy
      controls. Of the 11 patients with SAD, nine had repeat sumatriptan challenge
      following treatment with light therapy. The results showed that GH responses were
      significantly blunted during winter depression in patients with SAD compared to
      healthy controls. The GH responses normalized following treatment with light
      therapy to similar levels in controls. The results of this study provide a
      support for the role of serotonergic system in pathophysiology of SAD and in the
      mechanism of action of light therapy.

PMID- 9193739
TI  - Forskolin-stimulated platelet adenylyl cyclase activity is lower in persons with
      major depression.
AB  - We investigated platelet adenylyl cyclase activity in 17 subjects with a history
      of major depression ("depressed subjects") and 20 controls. Forskolin was used to
      directly activate adenylyl cyclase, while guanine nucleotides (Gpp(NH)p) and
      fluoride ions were used to measure adenylyl cyclase activity modulated through
      the G proteins. Forskolin-stimulated adenylyl cyclase was significantly lower in
      the depressed subjects (p < 0.0005). There was a statistically significant
      difference in basal adenylyl cyclase activity between male depressed subjects and
      male controls. The basal adenylyl cyclase activity was also lower in female
      depressed subjects, but this difference did not reach statistical significance (p
      < 0.2). The adenylyl cyclase activity measured after stimulation with a guanine
      nucleotide or cesium fluoride did not differ between control and depressed male
      or female subjects. Severity of current depression and the current use of
      antidepressant medication were not related to the lower forskolin-stimulated
      enzyme activity in the depressed subjects. The difference in forskolin-stimulated
      adenylyl cyclase activity appears to reflect a qualitative difference in the
      adenylyl cyclase enzyme activity in persons with a history of major depression.

PMID- 9193740
TI  - Reduced basal ganglia volumes in trichotillomania measured via morphometric
      magnetic resonance imaging.
AB  - A morphometric magnetic resonance imaging (MRI) study compared volumes of brain
      structures in 10 female subjects with trichotillomania (repetitive hair-pulling)
      versus 10 normal controls matched for sex, age, handedness, and education. Three
      dimensional MRI scans were blindly normalized and segmented using well
      characterized semiautomated intensity and differential contour algorithms by
      signal intensity-frequency histograms. Consistent with one a priori hypothesis,
      left putamen volume was found to be significantly smaller in trichotillomania
      subjects as compared with normal matched controls. This is the first report of a
      structural brain abnormality in trichotillomania. Results are discussed in terms
      of putative relationships between trichotillomania, Tourette's syndrome, and
      obsessive-compulsive disorder.

PMID- 9193741
TI  - Psychophysiological and clinical value of event-related potentials in obsessive
      compulsive disorder.
AB  - To investigate brain correlates of cognitive function in obsessive-compulsive
      disorder (OCD), event-related potentials (ERPs) were recorded in a group of
      thirteen unmedicated OCD patients and thirteen normal controls for verbal
      auditory stimuli in an oddball paradigm. The patients showed longer latencies of
      the N1 and P2, shorter latency of the P3, and reduced amplitude of the N2. These
      results suggest that OCDs stress the speed of task-dependent processes (i.e., by
      showing shorter N2 and P3 latencies) and have impairment of task-independent ones
      (i.e., by showing longer N1 and P2 latencies and reduced N2 amplitude). The
      components were more positive in the left hemisphere in OCDs and in the right
      hemisphere in normal controls. Future responders to treatment had significantly
      reduced N2 and enhanced P3 amplitudes relative to future nonresponders. So ERPs
      might provide psychophysiological profiles in OCDs with clinical and
      pharmacological implications.

PMID- 9193743
TI  - High sialic acid reactivity of sugar chain structure Lewis-X in patients with
      mental retardation.
AB  - It has been reported that platelet-derived growth factor B-chains homodimer (PDGF
      BB) improves learning function of mice, and that sugar chain structure Lewis-X of
      N-glycosylated glycoprotein promotes PDGF-BB secretion from platelets. Based on
      these findings, we assumed that learning dysfunction in some patients with mental
      retardation might be due to abnormality in PDGF-BB metabolism and/or Lewis-X
      structure. No difference in the reactivity of PDGF-BB and Lewis-X was found
      between the serum of patients with mental retardation and that of normals. But
      sialic acid reactivity of the Lewis-X fraction in some patients was remarkably
      higher than that in other patients and in normals. These findings suggest that
      sialic acids in the Lewis-X fraction may have a relation to one of the causes of
      learning dysfunction in these patients.

PMID- 9193742
TI  - Neuroelectric correlates of response production and inhibition in individuals at
      risk to develop alcoholism.
AB  - P300 recordings were made from males at high risk (HR) for alcoholism and low
      risk (LR) controls, participating in a visual go/no go reaction time paradigm.
      The go (button press) and no go (inhibit response) stimuli were large and small
      forms of the same letters. The LR group had significantly larger go than no go
      P300 amplitudes in the central, parietal, and temporal regions; the HR group
      manifested no response differences in any region. In the LR group compared to the
      HR group, both go and no go response amplitudes were larger over the entire head;
      no group differences in latencies were observed in any region. Surface energy
      magnitudes paralleled P300 amplitudes and were also larger in the LR group during
      both go and no go trials. Our findings indicate that HR individuals manifest
      widespread P300 amplitude deficits while performing a simple information
      processing paradigm. These deficits, which may reflect genetic influences,
      preceded the onset of alcoholism and may function as a phenotypic marker for its
      development.

PMID- 9193744
TI  - Autism and celiac disease: failure to validate the hypothesis that a link might
      exist.
AB  - Autism is a heterogeneous condition and the possible pathogenic role of several
      different factors has been postulated. Association between celiac disease and
      neurological manifestations such as drug resistant epilepsy and cerebral
      calcifications is well known. Some authors in the past also reported the
      existence of a linkage with autism. On the basis of these observations, we have
      evaluated 120 patients with celiac disease diagnosed at the Pediatric Clinic of
      the University of Catania, Italy, in order to identify behavioral problems and
      autistic features: there were 20 controls for this part of the study. At the same
      time, AGA and AEMAb were assayed in 11 patients with infantile autism and 11 age-
      and sex-matched controls. No celiac case was detected among the group of autistic
      patients and, although two of them had slightly increased levels of AGA IgG and
      AEMAb, subsequent antibodies determinations and jejunal biopsies gave normal
      results. Moreover none of the celiac patients had a positive DSM-III-R test for
      infantile autism.

PMID- 9193745
TI  - Anxiogenic effects of pentagastrin in patients with social phobia and healthy
      controls.

PMID- 9193746
TI  - Toxicity associated with high-dose cytosine arabinoside and total body
      irradiation as conditioning for allogeneic bone marrow transplantation.
AB  - Seventy-three patients with hematological cancers undergoing allogeneic bone
      marrow transplantation (BMT) were evaluated for event-free survival (EFS) and
      toxicity. All received 36 g/m2 cytosine arabinoside (HDA) and 1200 cGy
      fractionated total body irradiation (TBI). We assessed the association of EFS and
      toxicities with the following risk factors; age, gender, diagnosis, initial
      relapse risk and patient-donor histocompatibility. The EFS probability is 33% at
      800 days post-BMT. Twenty-six patients (36%) died of toxicity within 100 days and
      14 (19%) have relapsed. EFS was inversely associated with age (P < 0.0001) and
      initial relapse risk (P = 0.007). The risk of pulmonary (P = 0.023) and hepatic
      toxicity (P = 0.011) increased with age. Diagnosis other than acute lymphoblastic
      leukemia (ALL) was a risk factor (P = 0.015) for graft-versus-host disease
      (GVHD); and fewer ALL patients died from toxicity (P = 0.014). The probability of
      sepsis within 100 days post-BMT correlated (P = 0.007) with initial relapse risk.
      We conclude: (1) the lower EFS and greater pulmonary and hepatic toxicity
      associated with increasing age indicate a need for less toxic regimens that
      maintain high antileukemic efficacy for older patients; (2) the high GVHD and
      sepsis rates seen in certain categories of patients indicate a need for careful
      definition of eligibility criteria for this still highly toxic treatment.

PMID- 9193747
TI  - Outpatient total body irradiation for pediatric patients undergoing stem cell
      transplantation.
AB  - We have retrospectively reviewed the ability to safely deliver total body
      irradiation (TBI) in the outpatient setting in 10 pediatric patients undergoing
      stem cell transplantation. Patients had a median age of 14 years (range 9-17
      years) with diagnoses that included ALL in second remission, AML in second
      remission, myelodysplastic syndrome, Ewing's sarcoma, and rhabdomyosarcoma.
      Patients received a total of 1375 cGy or 1440 cGy given in a hyperfractionated
      schedule (11 or 12 fractions) over a 4-day period. All children were seen in the
      outpatient clinic daily during TBI and all were housed within a 20 mile radius of
      our institution during this period. Eight patients achieved good control of
      nausea and emesis with ondansetron alone while two patients required ondansetron
      and diphenhydramine. Nine patients received some form of intravenous hydration
      during this period (hyperalimentation, fluid boluses in clinic, or night-time
      intravenous fluids). One patient maintained good hydration with oral intake
      alone. Only one child required admission during this period for persistent nausea
      and vomiting despite antiemetics and intravenous fluids. A cost approximation
      suggests that TBI delivered in the outpatient setting resulted in a saving of
      approximately $2400 per patient. We conclude that TBI administered to children
      and adolescents in the outpatient setting can be a safe and cost-effective
      practice.

PMID- 9193748
TI  - Effect of T cell subset dose on outcome of T cell-depleted bone marrow
      transplantation.
AB  - T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in
      that the T cell receptor (TCR)gamma delta bearing subset is relatively spared
      compared to the TCR alpha beta + subset. We evaluated the probabilities of
      engraftment, acute and chronic graft-versus-host disease (GVHD), relapse, and
      survival in 273 recipients of marrow T cell depleted using T10B9. Sixty-two
      patients received marrow from an HLA-identical sibling, 54 patients received
      partially matched related donor marrow and 157 patients received unrelated donor
      marrow. Limiting dilution analysis (LDA) was used to estimate total clonable T
      cell dose in all patients and a modified LDA using moAb-coated immunomagnetic
      beads was used to estimate TCR alpha beta +, CD4+, and CD8+ T cells in a subset
      of patients. TCR gamma delta + cell dose was estimated by flow cytometry. Cox
      proportional hazards regression models were used to assess the impact of T cell
      subset dose/kg of body weight on outcome. We found a significant association of
      TCR gamma delta + T cell dose (P = 0.004), but not TCR alpha beta + T cell dose
      or total clonable T cell dose, with the probability of engraftment. TCR alpha
      beta +, CD4+, CD8+ and total clonable T cell dose were significantly associated
      (P < 0.001) with the risks of grade 2-4 acute GVHD in recipients of marrow from
      related donors but not in recipients of marrow from unrelated donors. Neither
      total clonable T cell dose nor any T cell subset dose was found to be
      significantly associated with chronic GVHD, relapse or survival. The results
      confirm preclinical studies showing TCR gamma delta + T cells promote
      engraftment. TCR gamma delta + T cells are not associated with an increased risk
      of acute GVHD while TCR alpha beta T cells are associated with acute GVHD but not
      engraftment in recipients of marrow grafts T cell depleted using T10B9. These
      findings support the hypothesis that T cell subsets differentially contribute to
      alloengraftment and GVHD.

PMID- 9193749
TI  - Clonogenic capacity and ex vivo expansion potential of umbilical cord blood
      progenitor cells are not impaired by cryopreservation.
AB  - Umbilical cord blood (UCB) progenitor cells have been demonstrated to possess
      significant advantages over bone marrow (BM), in terms of proliferative capacity
      and immunologic reactivity. Therefore, UCB has been recently considered an
      attractive potential alternative to BM as a source of hematopoietic progenitor
      cells for clinical applications. Since several programs throughout the world are
      currently evaluating the feasibility of large-scale UCB banking for unrelated
      transplants, it was the aim of this study to evaluate whether cryopreservation
      procedures might heavily impair the clonogenic capacity, the feasibility of CD34+
      selection and the ex vivo expansion potential of UCB progenitor cells. UCB
      samples were collected and cryopreserved as unseparated (n = 21) or mononuclear
      (MNC) cells (n = 15) within 12 h from delivery, and evaluated for viability,
      immunophenotype, cell and progenitor numbers after a minimum stay in liquid
      nitrogen of 6 months (range 6-14 months). Viability was always > 97% and no
      statistically significant difference was detected by flow cytometric analysis.
      Clonogenic recovery from unseparated cells was 80-87% for HPP-CFC, CFU-GEMM, BFU
      E and CFU-GM, and from MNC cells ranged from 82 to 91% for LTC-IC, CFU-GEMM, BFU
      E and CFU-GM. CD34+ selection (n = 8) was performed on fresh and cryopreserved
      MNC cells using the MiniMACS immunomagnetic separation device, showing no
      difference in yield (68 +/- 7% vs 57 +/- 4%, P < or = 0.4) or in purity (89 +/-
      2% vs 81 +/- 6%, < or = 0.4), for fresh in comparison to cryopreserved MNC cells.
      After 14 days of liquid culture in the presence of different combinations of SCF,
      IL-3, IL-6 and G-CSF no statistically significant difference was detected in CFC
      fold-expansion for fresh or cryopreserved MNC cells and for CD34+ cells, either
      selected and cultured from fresh or cryopreserved MNC cells. In conclusion we can
      state that UCB is a potential source of primitive progenitor cells that can be
      cryopreserved unmanipulated or after physical separation without major losses in
      clonogenic capacity and immunophenotypic composition. Moreover, CD34+ selection
      from cryopreserved MNC cells is feasible and ex vivo expansion is not impaired.
      These results have important implications in the large scale UCB banking, in view
      of the potential applications of ex vivo expanded hematopoietic progenitor cells
      for the engraftment of adult patients.

PMID- 9193750
TI  - Conditioning with cyclophosphamide/antithymocyte globulin for allogeneic bone
      marrow transplantation from HLA-matched siblings in children with severe aplastic
      anemia.
AB  - Graft rejection has been a problem after bone marrow transplantation for patients
      with severe aplastic anemia (SAA). Ten children with SAA were conditioned for
      bone marrow transplantation from HLA-identical siblings, using cyclophosphamide
      (CY, 50 mg/kg) plus antithymocyte globulin (ATG, 15 mg/kg) for 4 successive days.
      Marrow was infused 36 h after the last dose of CY. Cyclosporin A and methotrexate
      were administered as graft-versus-host disease (GVHD) prophylaxis. All patients
      achieved durable engraftment at follow-up of 7-41+ months (mean, 25) without
      significant GVHD. Since investigators have used different sources, doses, and
      time schedules of ATG, we compared our results with other published reports. We
      conclude that CY/ATG conditioning is well tolerated and effective in children
      with SAA.

PMID- 9193751
TI  - Erythroid burst-forming units (BFU-E) predict hematopoietic recovery after
      peripheral blood progenitor cell transplantation in patients with advanced breast
      cancer.
AB  - In 29 consecutive heavily pretreated stage IV breast cancer patients, we analyzed
      patient factors and in vitro characteristics of peripheral blood progenitor cell
      (PBPC) collections that might correlate with the speed of hematopoietic recovery
      after autologous transplantation. PBPC collections were assessed for total number
      of mononuclear cells infused/patient weight in kg and hematopoietic progenitor
      cell content using in vitro colony-forming assays. In these patients, who
      received PBPC as the sole hematopoietic support after myeloablative chemotherapy,
      the number of erythroid burst-forming units (BFU-E) infused correlated
      significantly with both time to neutrophil (P = 0.008) and platelet (P = 0.0001)
      recovery and was a better predictor of hematopoietic recovery than number of CFU
      GM administered. By day 75 after transplantation, six patients with poor BFU-E
      yields failed to engraft platelets. Our data suggest that the number of BFU-E
      infused correlate with time to hematopoietic engraftment and may predict failure
      of platelet engraftment in heavily pre-treated patients.

PMID- 9193752
TI  - CD34 positive PBPC expanded ex vivo may not provide durable engraftment following
      myeloablative chemoradiotherapy regimens.
AB  - We have previously demonstrated that CD34+ cells, selected from peripheral blood
      progenitor cells (PBPC), can be expanded in ex vivo culture and can be infused in
      tandem with unmanipulated PBPC with little or no toxicity. In this study, four
      patients (two non-Hodgkin's lymphoma (NHL), two multiple myeloma (MM)) received
      myeloablative conditioning prior to stem cell rescue using ex vivo expanded cells
      alone. The two patients with NHL received cyclophosphamide and total body
      irradiation (CY/TBI) and the two patients with MM, busulphan and melphalan
      (Bu/M). One case received an inadequate CFU-GM dose, despite expansion, and in
      one case the expanded cells were contaminated. No definitive conclusions may
      therefore be drawn concerning engraftment in these two cases. However, the other
      two cases received high doses of committed progenitors. Following infusion of the
      expanded material, all four patients failed to show sustained neutrophil
      engraftment and none showed evidence of platelet engraftment. Back-up,
      unmanipulated PBPC were therefore infused on days 14, 34, 32 and 28 and
      subsequently all four cases achieved satisfactory engraftment of both neutrophils
      and platelets. In conclusion, we feel that, CD34+ cells, expanded ex vivo using
      the conditions described in this report, may not provide durable engraftment
      following fully myeloablative conditioning.

PMID- 9193754
TI  - Screening for CMV-specific T cell proliferation to identify patients at risk of
      developing late onset CMV disease.
AB  - Thirty patients undergoing allogeneic BMT were screened post-transplant together
      with their marrow donors for CMV-specific T cell proliferation and the occurrence
      of CMV disease. Twenty-one of these patients received a marrow transplant from an
      HLA-matched sibling donor, and nine from an HLA-matched unrelated donor. All
      these patients were either CMV seropositive and/or had received a transplant from
      a CMV-seropositive donor. Patients were monitored for CMV-viraemia until day +100
      post-BMT by PCR and virus culture, and thereafter by virus culture only when
      clinically indicated. The proliferative T cell response was investigated at
      regular monthly intervals beginning on day +30. A proliferative response to HCMV
      (median, day +123) was documented in these patients between day +37 and +730 post
      BMT. None of the patients with a documented CMV-specific T cell proliferation on
      day 120 (n = 17) developed CMV disease in the later post-transplant period, but
      of the patients lacking CMV-specific proliferation (n = 13), 30.8% developed CMV
      disease after day 120. Thus, patients lacking a CMV-specific T-helper cell
      response might benefit from sensitive screening for CMV infection and pre-emptive
      therapy after day +100.

PMID- 9193753
TI  - Engraftment and outcomes of patients receiving myeloablative therapy followed by
      autologous peripheral blood stem cells with a low CD34+ cell content.
AB  - Engraftment kinetics after high-dose chemotherapy (HDC) were evaluated in
      patients receiving autologous peripheral blood stem cell (PBSC) infusions with a
      low CD34+ cell content. Forty-eight patients were infused with < 2.5 x 10(6)
      CD34+ cells/kg; 36 because of poor harvests and 12 because they electively
      received only a fraction of their harvested cells. A median of 2.12 x 10(6) CD34+
      cells/kg (range, 1.17-2.48) were infused following one of seven different HDC
      regimens. All patients achieved absolute neutrophil counts > or = 0.5 x 10(9)/l
      at a median of day 11 (range, 9-16). Forty-seven patients achieved platelet
      counts > or = 20 x 10(9)/l at a median of day 14 (range, 8-250). Nine of 47 (19%)
      had platelet recovery after day 21, 4/47 (9%) after day 100 and one died on day
      240 without platelet recovery. Twenty-six patients (54%) died of progressive
      disease in 51-762 days; 22 (46%) are alive at a median of 450 days (range, 94
      1844), 17 (35%) of whom are surviving disease-free at a median of 494 days
      (range, 55-1263). No patient died as a direct consequence of low blood cell
      counts. These data demonstrate that PBSC products containing 1.17-2.48 x 10(6)
      CD34+ cells/kg resulted in relatively prompt neutrophil recovery in all patients
      but approximately 10% had delayed platelet recovery.

PMID- 9193755
TI  - What happens subsequently in AML when cytogenetic abnormalities persist at bone
      marrow harvest? Results of the 10th UK MRC AML trial. Medical Research Council
      Leukaemia Working Parties.
AB  - Cytogenetic analysis performed at diagnosis is widely recognised to provide one
      of the most valuable prognostic indicators in AML. Yet any role for this
      technique in residual disease assessment, particularly in the context of
      subsequent transplantation procedures has been incompletely explored. The present
      study considers the outcome of 190 patients drawn from the UK MRC AML 10 trial in
      whom cytogenetics were assessed whilst in morphological CR at the time of bone
      marrow harvest. Cytogenetics at this stage were abnormal in 19 patients (10%). In
      11/19 patients, the abnormalities detected reflected the acquisition of new
      clonal (3/11) or nonclonal changes (8/11) that were not identified at diagnosis;
      comparison of this group to patients with normal cytogenetics at harvest provided
      no evidence that such acquired changes are of prognostic significance. In 8/19
      patients, abnormalities detected were indicative of persistence of the disease
      related clone in harvested marrow. Two of these patients died of sepsis during
      consolidation therapy. Two received ABMT in first morphological CR: one patient
      with AML associated with a favourable karyotype (+8,inv(16)) remains in CR, 5.5
      years post-transplant, whereas the other with cytogenetic abnormalities
      considered to confer a poor prognosis (inv(3q),-7), relapsed within 5 months of
      ABMT. All four of the remaining patients with cytogenetic evidence of persistent
      disease who were not transplanted in first CR, relapsed within 6.5 months of
      harvest. Therefore, among 101 of 190 patients with AML characterised by abnormal
      karyotype at diagnosis, persistence of the disease-related clone in eight
      patients (8%), revealed by conventional cytogenetic assessment at bone marrow
      harvest whilst in morphological remission, was found to predict a poor prognosis.
      Nevertheless, transplantation procedures using marrow which is obviously
      contaminated with the original leukaemic clone may occasionally still be
      associated with long-term survival.

PMID- 9193756
TI  - PML is expressed in chronic graft-versus-host disease lesions.
AB  - The PML (for 'ProMyelocytic Leukemia') gene product is a nuclear zinc finger
      protein, identified when the chromosomal translocation fusing this gene to the
      retinoic acid receptor was found in acute promyelocytic leukemia. Recently, a
      frequent occurrence of autoantibodies against the PML protein was detected in
      primary biliary cirrhosis (PBC) sera, suggesting that this protein could
      represent an autoantigenic trigger in PBC. Chronic GVHD features are close to
      those of PBC and in addition, antinuclear and antinucleolar antibodies are
      frequently detected in patients' sera. In order to determine if an abnormal
      expression of PML, followed by the development of anti-PML antibodies, can be
      implicated in chronic GVHD pathogenesis, we studied the expression of PML in the
      skin of seven patients with chronic GVHD as well as the presence of circulating
      anti-PML antibodies. PML was highly expressed by the lesional skin keratinocytes,
      but circulating antibodies were never detected. PML is induced by interferon
      (IFN) gamma. The expression of PML by GVHD epidermis is likely secondary to the
      IFN gamma produced by infiltrating lymphocytes. Since PML display growth
      suppressor properties, the role of this protein in tissue lesions is discussed.

PMID- 9193757
TI  - Quality of life following bone marrow transplantation: a comparison of patient
      reports with population norms.
AB  - All surviving patients who had received an allogeneic bone marrow transplant at
      the Princess Margaret Hospital were asked to participate in a health-related
      quality of life (HQL) study using the Medical Outcomes Survey-Short Form 36 (MOS
      SF-36), the Satisfaction with Life Domains Scale-Bone Marrow Transplantation
      (SLDS-BMT) and a current symptoms checklist. The main objective was to compare
      the health status of BMT survivors with age-adjusted population norms. Of the 251
      patients contacted, 93% returned questionnaires. The median follow-up after BMT
      was 40 months, ranging from 1-253 months. On average, survivors had some
      diminished HQL relative to the health status of the population in general. Time
      since transplant had a significant influence on HQL; those less than 3 years from
      transplant experienced considerable impairment while those who had survived
      beyond this point were indistinguishable from the normal population in most
      domains and significantly better in certain psychosocial aspects of health. Many
      patients still reported symptoms months after BMT; some were mildly affected
      while others experienced more troublesome symptoms. However, 81% of patients were
      satisfied with the HQL outcome that they had achieved and 94% would recommend a
      transplant for someone in similar circumstances.

PMID- 9193758
TI  - Generation of normal lymphocyte populations following transplantation of
      adenosine-deaminase-deficient fetal liver cells.
AB  - Adenosine-deaminase-deficient mice were generated to investigate the role of
      adenosine deaminase (ADA) in lymphocyte maturation and to test treatment options
      for the severe combined immunodeficiency (SCID) associated with the absence of
      ADA in man. Whereas either genetic absence or postnatal inhibition of ADA affect
      primarily the haematopoietic system in both humans and mice, ADA-deficient mice
      die in the perinatal period. Consequently, we haematopoietically reconstituted
      lethally irradiated wild-type recipient mice with ADA-deficient fetal liver
      cells. Although the liver cells of gestational day 14 ADA-deficient murine
      embryos appeared metabolically deranged, their in vivo and in vitro colony
      forming capacities were similar to those of wild-type embryos. Lethally
      irradiated wild-type mice transplanted with ADA-deficient fetal liver cells
      appeared immunologically normal. Following mitogen stimulation, their splenocytes
      and thymocytes were more sensitive to deoxyadenosine than those from wild-type
      fetal liver chimaeras. This feature, characteristic of ADA-deficiency, indicated
      that mature and active lymphocytes were generated from ADA-deficient fetal liver
      cells following transplantation into wild-type hosts. Because approximately 20%
      of the haematopoietic cells appeared recipient-derived, it can not be concluded
      that the murine haematopoietic system can do without ADA-producing cells.

PMID- 9193759
TI  - Counterflow centrifugal elutriation as a method of T cell depletion may cause
      loss of immature CD34+ cells.
AB  - Counterflow centrifugal elutriation (CCE) is capable of separating cells on the
      basis of size. CCE has been used successfully to deplete allogeneic bone marrow
      (BM) grafts of T lymphocytes to decrease the risk of acute graft-versus-host
      disease. Previous studies have shown that more immature CD34+ cells in human BM
      tend to be smaller than more mature CD34+ cells. Human BM was subjected to CCE
      with the 4 ml standard chamber at constant rotor speed (2300 r.p.m.) and
      increasing flow-rate (14-23 ml/min, rotor-off). The eleven fractions collected
      were assayed for CD34+ and CD3+ cells, and for CFU-GM, HPP-CFC and long-term
      culture initiating cells (LTC-IC). The CD3+ T cells were enriched in the early
      (small-cell) fractions 14-17 ml/min. CD34+ cells were enriched in fractions 17-21
      ml/min, and CFU-GM were concentrated in the same fractions. HPP-CFC and LTC-IC
      showed nearly identical CCE profiles, with enrichment in fractions 16-18 ml/min.
      When fraction < or = 17 ml/min was chosen as cut-off, the small-cell fraction
      contained 94.0% of all CD3+ cells, 44.4% of total cells, 33.2% of CD34+ cells and
      34.7% of CFU-GM; however, 67.6% of HPP-CFC and 72.4% of LTC-IC were recovered in
      this small-cell fraction. These data suggest that T cell depletion through CCE as
      used by us, while losing only minor proportions of CD34+ cells and CFU-GM,
      carries the risk of losing the majority of more immature progenitor cells. This
      may lead to an increased risk of graft failure, in particular in HLA-mismatched
      transplants.

PMID- 9193760
TI  - Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone
      marrow transplantation to immunotherapy with interferon-alpha 2b.
AB  - A patient with acute myeloid leukemia secondary to therapy of choriocarcinoma
      underwent T cell non-depleted allogeneic bone marrow transplantation from an
      unrelated donor in first untreated relapse. Persistent/relapsed leukemia 4 months
      after transplantation did not respond to cessation of cyclosporine. Due to
      logistic difficulties in obtaining donor leukocytes, she was treated with
      interleukin-2 and interferon-alpha 2b. Although the interleukin could be
      administered for a short period only, the interferon was continued for 4 months.
      Interferon was stopped when limited chronic graft-versus-host disease developed,
      but was followed by extramedullary and early marrow relapse. Reinstitution of
      interferon resulted in the development of scleroderma-like extensive chronic GVHD
      and remission. Interferon was given for 5 months. GVHD improved slowly with
      treatment, but scleroderma-like changes still persist. The patient is alive with
      no evidence of disease and a Karnofsky score of 90% 41 months after relapse and
      26 months after stopping cyclosporine. We conclude that cytokines alone may
      occasionally result in a durable response of acute leukemia relapsing after
      allografting, and should be considered in patients with a low tumor burden if it
      is difficult to obtain donor cells.

PMID- 9193761
TI  - Early and fatal immune haemolysis after so-called 'minor' ABO-incompatible
      peripheral blood stem cell allotransplantation.
AB  - A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from
      his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of
      the donor were low. Allogeneic peripheral blood stem cells were harvested by
      leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment
      occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant.
      At this time a severe immune haemolytic syndrome occurred and direct antiglobulin
      test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution
      was rapidly unfavourable related to multiorgan failure. The patient died on day
      +20 post-transplant.

PMID- 9193762
TI  - Flow cytometric cell sorting combined with molecular chimerism analysis to detect
      minimal recurrent leukemia: good news and bad news.
AB  - Allogeneic BMT offers the possibility of cure for a variety of hematopoietic
      malignancies, but disease relapse remains a major cause of treatment failure.
      This report describes two cases in which flow cytometric cell sorting (FACS) and
      molecular chimerism analysis were combined to increase the sensitivity of minimal
      residual disease (MRD) detection. In the first case this approach was used to
      demonstrate that a suspicious phenotype was not recurrent leukemia, thus
      preventing the use of potentially toxic therapy. In the second case the
      recurrence of a leukemia which was undetectable by conventional analysis was
      confirmed. The potential benefits of combining these MRD detection methods are
      discussed.

PMID- 9193763
TI  - Where is the "neuro" in psychoneuroimmunology? A commentary on increasing
      research on the "neuro" component of psychoneuroimmunology.
AB  - The role of the central nervous system in generating the interrelationships among
      stress, endocrine and peripheral immune function, and disease receives relatively
      little experimental attention. This commentary encourages a greater emphasis on
      such research with a particular emphasis on the use of electrophysiological and
      neural imaging techniques.

PMID- 9193764
TI  - Stressor-induced alterations in immune response and viral clearance following
      infection with herpes simplex virus-type 1 in BALB/c and C57B1/6 mice.
AB  - Extending earlier studies of stress-induced modulation of herpes simplex virus
      (HSV) infection and immunity, we investigated the effects of electric foot shock
      (0.3 mA) on cytokine production and immune effector function in response to a
      nonlethal inoculum of HSV-1 in two strains of inbred mice, C57B1/6 and BALB/c.
      Increased levels of infectious virus at the site of infection were observed in
      foot-shocked mice of both strains compared to control mice. The specific pattern
      of changes in interleukin (IL)-2 and interferon-gamma, as well as IL-4 and IL-10,
      induced by foot-shock stress differed between the two strains. IgM anti-HSV
      antibody responses were, however, increased in both strains.

PMID- 9193765
TI  - Response of human oligodendrocytes to interleukin-2.
AB  - Interleukin 2 (IL-2) directly affects the function of both neurons and glia in
      the nervous system. It can induce proliferation and differentiation or cause cell
      death in oligodendrocytes. We have previously cloned the cDNAs for the alpha
      (alpha), beta (beta), and gamma (gamma) chains of the IL-2 receptor (IL-2R)
      complex from a human oligodendroglioma cell line TC620. In an effort to
      characterize the IL-2 receptor (IL-2R) on oligodendrocytes, experiments were
      performed using recombinant human IL-2 on normal human oligodendrocytes from
      adult brain tissue and the IL-2-responsive subclone TC620.6A2 of the
      oligodendroglioma line. The TC620 subclone has the phenotype of an immature
      oligodendrocyte. At 5 nM IL-2, there was a 2.5-fold increase in proliferation of
      both normal and malignant human oligodendrocytes. This response was receptor
      mediated in that binding of 125I-IL-2 to TC620.6A2 cells detected a single
      receptor class for IL-2 with an affinity of 3.6 nM. Immunohistochemical staining
      of TC620.6A2 cells with a panel of monoclonal antibodies to different epitopes of
      the human IL-2R alpha chain demonstrated the presence of IL-2R alpha on the
      surface of these cells, in staining patterns which did not always coincide with
      those found on T cells. Neither the beta nor the gamma chain of the IL-2R complex
      was detected on human oligodendrocytes by immunohistochemistry. Those antibodies
      which recognized cell surface IL-2R alpha epitopes on TC620.6A2 blocked IL-2
      induced proliferation, while those which did not detect cell surface IL-2R alpha
      epitopes were not inhibitory. This same panel of monoclonal antibodies, when used
      to probe membrane preparations of TC620.6A2 cells on a Western blot, detected
      three proteins of 100, 83, and 47 kDa, in contrast to the 55-kDa IL-2R alpha
      observed on T cells.

PMID- 9193766
TI  - Involvement of intracellular Ca2+ during growth hormone-induced priming of human
      neutrophils.
AB  - Growth hormone (GH) primes and augments O2- production in neutrophils. The exact
      signaling of the priming pathway by GH has not been demonstrated. In this study,
      we investigated intracellular signaling of priming by recombinant human growth
      hormone (rGH) in human neutrophils. A low concentration of rGH (10-100 ng/ml)
      significantly enhanced the O2- production from neutrophils triggered with N
      formyl-1-methionyl-1-leucyl-1-phenylalanine in a dose-dependent manner.
      Recombinant GH directly increased the fluorescence intensity of intracellular
      Ca2+ labeled with fluo 3-AM in neutrophils. The change of fluorescence intensity
      of cytosolic Ca2+ was dependent on the rGH concentration. The peak level of
      fluorescence intensity was observed at 3 to 5 min after treatment with rGH. The
      priming effect of rGH on O2- production via Ca2+ was abrogated by Ca2+ channel
      blockers such as dentrolene and verapamil. Furthermore, preincubation with
      genistein, a tyrosine kinase inhibitor, blocked the rGH-induced increases in Ca2+
      and O2- production. This finding suggests that GH can act through the increase of
      intracellular Ca2+ as a priming agent to activate neutrophils for an enhanced
      respiratory burst.

PMID- 9193767
TI  - Psychosocial influences on immune responses to HSV-1 infection in BALB/c mice.
AB  - The effects of differential housing (one or four mice/cage) on T-helper (Th) cell
      markers of cellular and humoral immune responses were examined. Differentially
      housed male BALB/cJ mice were infected with herpes simplex virus (HSV)-1 (Patton
      strain), and in vitro cytokine production [interleukin (IL)-2, IL-4, IL-10, and
      interferon (IFN)-gamma] by splenocytes and popliteal lymph node cells and serum
      antibody titers (IgM and IgG) were evaluated. Differential housing of male BALB/c
      mice influenced the magnitude, but not the kinetics, of some, but not all, immune
      responses to HSV-1. Splenocytes from individually housed mice produced more IL-2,
      IFN-gamma, IL-4, and IL-10 than splenocytes from group-housed mice; in popliteal
      lymph node cells, only IFN-gamma and IL-10 production was influenced by housing.
      Although the social environment influenced cytokine production, there were no
      concomitant changes in circulating IgM or IgG antibody titers. These results do
      not support the hypothesis that dominant Th cell responses are the primary
      targets of this psychosocial manipulation, or that a reciprocal relationship
      exists between Th1 and Th2 cell-derived cytokines.

PMID- 9193768
TI  - Influence of psychogenic and neurogenic stressors on endocrine and immune
      activity: differential effects in fast and slow seizing rat strains.
AB  - Variations of plasma ACTH and corticosterone, as well as splenic macrophage
      activity and mitogen-induced cell proliferation, were determined in rats
      following 15 min of either the neurogenic stressor of restraint or by a purely
      psychogenic stressor consisting of exposure to a ferret. The effects of these
      stressors were assessed in two strains of rats that were selectively bred for
      either Fast or Slow kindling epileptogenesis triggered in response to amygdala
      stimulation. The stressors differentially influenced behavioral responses,
      endocrine activity, and immune functioning, and these effects varied with the
      strain of rat. In response to restraint the Fast rats exhibited protracted
      struggling, while the Slow rats tended to be immobile. In contrast, upon ferret
      exposure the Fast rats showed greater immobility than the Slow rats. The
      stressors also induced marked elevations of plasma ACTH and corticosterone.
      Whereas the ACTH and corticosterone increases were more pronounced in response to
      the ferret in the Slow rats, restraint resulted in a markedly greater rise of
      plasma ACTH in the Fast strain. Proliferation of splenic lymphocytes in response
      to Con A and LPS were elevated in Fast seizing rats, while macrophage activity,
      as determined by oxygen burst following addition of PMA and luminol to splenic
      mononuclear cells, was greater in the Slow seizing strain. While neither stressor
      influenced cell proliferation in either the Fast or Slow rats, macrophage
      activity was greatly suppressed by ferret exposure only in the Slow rats. Taken
      together, it appears that while stressors influence behavior and immune and
      endocrine functioning, these effects may vary as a function of the interaction of
      the strain of rat and the specific type of stressor employed.

PMID- 9193769
TI  - Helicobacter pylori, gastric cancer and gastric MALT lymphoma.

PMID- 9193770
TI  - Segmental colitis complicating diverticular disease.
AB  - Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients
      with underlying diverticulosis are presented. Segmental resection has permitted
      close review of the histopathology in this syndrome which demonstrates
      considerable similarity to changes seen in idiopathic ulcerative colitis. The
      reported experience with this syndrome and its clinical features are reviewed.

PMID- 9193771
TI  - Methotrexate hepatotoxicity in psoriatics: report of 104 patients from Nova
      Scotia, with analysis of risks from obesity, diabetes and alcohol consumption
      during long term follow-up.
AB  - BACKGROUND AND DESIGN: Methotrexate (MTX) hepatotoxicity in psoriatic patients is
      well recognized, but there are discrepancies in the reported incidence and
      associated risk factors. This retrospective study describes 104 Nova Scotian
      patients with psoriasis seen between 1979 and 1990. Patients received MTX over
      one to 11 years (mean 3.38), with baseline and annual follow-up liver biopsies.
      Clinical data were obtained by chart review. Statistical analysis evaluated the
      risks associated with obesity, diabetes, alcohol consumption and duration of
      therapy, with the histological grade of liver biopsies. RESULTS: Of the 104
      patients, 35 were obese, 10 were diabetic and 37 occasionally consumed alcohol.
      At the end of the study, 21 patients had developed severe hepatic fibrosis (grade
      IIIB), and three developed liver cirrhosis (grade IV). Significant risk of severe
      hepatotoxicity is related to diabetes (P = 0.02) but not to obesity (P = 0.12) or
      alcohol consumption (P = 0.12). All patients with cirrhosis took MTX for two
      years in standard doses of 20 to 25 mg/week. CONCLUSIONS: In this first Canadian
      study evaluating MTX hepatotoxicity in psoriatics, the incidence of severe
      hepatotoxicity is high: 23.1% (24 of 104 patients). This study shows that
      diabetic patients are particularly at increased risk of MTX hepatotoxicity.
      Occasional alcohol consumption is not associated with increased risk. Three
      patients who developed cirrhosis over two years of standard MTX therapy may
      represent a subset of psoriatics with increased hepatic susceptibility to MTX.
      Another three patients whose severe hepatic fibrosis had regressed upon
      discontinuation of MTX, but who developed accelerated recurrence of the severe
      hepatic fibrosis upon resumption of MTX therapy, also suggest the possibility of
      unusual sensitivity to the drug. These cases emphasize the need for continuing
      surveillance, with regular liver biopsies, of psoriatic patients on MTX.

PMID- 9193773
TI  - Comparison of the utilization of endoscopy units in selected teaching hospitals
      across Canada.
AB  - There is no information on the number of endoscopic procedures performed at major
      teaching hospitals across Canada. The directors of endoscopy units at eight
      teaching hospitals from Halifax to Vancouver volunteered demographic information
      on the unit at their location. There was a very wide range of endoscopic
      utilization, with approximately comparable rates of out-patient versus in-patient
      procedures and of gastroscopies versus colonoscopies, but there was no obvious
      linking of the ratios of in-patients:out-patients versus total number of
      designated gastrointestinal beds or total number of hospital beds. Thus, the
      appropriateness of endoscopic procedures needs to be based on standards of
      practice and accepted indications. The number of endoscopies performed per
      endoscopy unit support staff varied widely (from 323.7 to 1065.3 per year), and
      it would be interesting to learn whether this represents an opportunity for cost
      saving in some units.

PMID- 9193772
TI  - Late acute rejection occurring in liver allograft recipients.
AB  - To study the effect of immunosuppressive reduction on the incidence and
      consequence of late acute rejection (LAR) in liver allograft recipients, mean
      daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were
      retrospectively reviewed for the nearest 12-week period preceding six episodes of
      LAR in five liver allograft recipients (group 1). Results were compared with
      those from a cohort of 12 liver allograft recipients who did not develop LAR
      (group 2). LAR was defined as acute rejection occurring more than 365 days post
      transplantation. Median follow-up for both groups was similar (504 days, range
      367 to 1050, versus 511 days, range 365 to 666, not significant). Mean trough CsA
      levels were lower in patients with LAR compared with those without (224 +/- 66
      ng/mL versus 233 +/- 49 ng/mL) but the difference was not statistically
      significant. In contrast, mean daily prednisone dose (2.5 +/- 1.6 mg/day versus
      6.5 +/- 2.9 mg/day, P = 0.007) and CsA nadir values (129 +/- 60 ng/mL versus 186
      +/- 40 ng/mL, P = 0.03) were significantly lower in patients who developed LAR
      compared with those who did not. Five of six episodes (83%) of LAR occurred in
      patients receiving less than 5 mg/day of prednisone, versus a single LAR episode
      in only one of 12 patients (8%) receiving prednisone 5 mg/day or more (P =
      0.004). In all but one instance, LAR responded to pulse methylprednisolone
      without discernible affect on long term graft function. The authors conclude that
      liver allograft recipients remain vulnerable to acute rejection beyond the first
      post-transplant year; and reduction of immunosuppressive therapy, particularly
      prednisone, below a critical, albeit low dose, threshold increases the risk of
      LAR.

PMID- 9193774
TI  - Biliary sludge: a risk factor for 'idiopathic' pancreatitis?
AB  - Idiopathic acute pancreatitis is common. Recent evidence suggests that biliary
      sludge may be the etiology in many patients with this disorder. In this case
      control study, admission ultrasound examinations of patients with idiopathic
      pancreatitis, patients with acute alcohol-associated pancreatitis and a control
      group were compared. Biliary sludge was found in seven of 21 patients (33%) with
      idiopathic pancreatitis, two of 25 (8%) with acute alcohol-associated
      pancreatitis and one of 63 controls (1.6%). Comparison of idiopathic pancreatitis
      patients with both acute alcohol-associated pancreatitis patients and controls
      for the presence of sludge revealed odds ratios of 31.0 (95% CI 3.5 to 273) and
      5.8 (95% CI 1.1 to 32.0), respectively. Also observed was a trend towards higher
      levels of liver enzymes, bilirubin and amylase in patients with idiopathic
      pancreatitis who had sludge identified. This study provides further evidence
      linking biliary sludge with a significant proportion of patients with idiopathic
      acute pancreatitis.

PMID- 9193775
TI  - Elevated aminotransferase activity as an indication of muscular dystrophy: case
      reports and review of the literature.
AB  - Five male children are reported in whom incidental recognition of elevated serum
      alanine aminotransferase (ALT) activity initiated investigation to identity the
      cause of suspected hepatocellular injury. All five were later diagnosed with X
      chromosome-linked muscular dystrophy. The serum level of ALT, generally
      considered to be specific for hepatocellular injury, was increased two to 25
      times above normal in all the reported cases. Paradoxically, the increase in ALT
      activity was greater than that of serum aspartate aminotransferase (three to 16
      times normal), an enzyme whose elevation is generally recognized as being less
      specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or
      hepatic injury. At presentation to the gastrointestinal service, one case, age
      2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the
      other four had previously unrecognized hypertrophy of the calves, proximal limb
      weakness, positive Gower's sign or delayed gross motor skills. All five patients
      had marked elevation of serum creatine kinase activity and histopathologically
      confirmed muscular dystrophy. The practical clinical implication of this report
      is that children with elevated serum ALT, in the absence of other signs and
      symptoms of hepatic injury, may have occult muscular disease--most frequently
      muscular dystrophy. Although the clinical signs of muscular dystrophy may be
      subtle or absent, early determination of creatine kinase will suggest the correct
      diagnosis and minimize extensive and invasive investigation focusing on hepatic
      injury.

PMID- 9193776
TI  - Immunocytochemical and morphometric studies of gastrin-, somatostatin- and
      serotonin-producing cells in the stomach and duodenum of patients with acid
      peptic disorders.
AB  - Gastric and duodenal biopsies from 90 patients with various acid peptic disorders
      reflux esophagitis (n = 24), gastric ulcer (n = 13), duodenal ulcer (n = 47) and
      nonulcer dyspepsia (n = 6)-were examined. Seven patients with minimal dyspeptic
      symptoms and an endoscopically and histologically normal stomach and duodenum
      served as controls. Immunoperoxidase staining for gastrin-producing G cells,
      somatostatin-producing D cells and serotonin-producing EC cells was carried out
      on fundic, antral and duodenal biopsies, and was quantified using a Zeiss MOP
      Videoplan using the peroxidase-antiperoxidase technique of Sternberger. In the
      gastric antrum, a G:D:EC cell ratio of approximately 1.6:1:1-was observed. In the
      duodenum the corresponding ratio was 1:1:2.4. No significant differences were
      observed within any of the major diagnostic categories. Patient age, sex,
      duration of symptoms, smoking habits, alcohol consumption and nonsteroidal anti
      inflammatory drug use had no effect on endocrine cell densities. Reduced G cell
      density in the descending duodenum was observed in the presence of mild
      duodenitis in four patients. In four patients with evidence of antral intestinal
      metaplastic changes, a significant increase in duodenal G cell densities was
      found. These results suggest that a change in the number of G, D or EC cells does
      not play a primary role in the pathophysiology of acid peptic disorders in the
      majority of patients.

PMID- 9193777
TI  - AIDS-related extrapulmonary Pneumocystis carinii infection presenting as a
      solitary rectal ulcer.
AB  - Extrapulmonary infection with Pneumocystis carinii, although uncommon, is
      increasingly recognized. Use of aerosolized pentamidine versus a systemic
      medication is thought to be a contributing factor due to the low concentrations
      of drug that are incapable of suppressing systemic infection. Infection with P
      carinii has been reported in every organ system including the gastrointestinal
      system. A 28-year-old acquired immunodeficiency syndrome patient receiving
      prophylaxis with aerosolized pentamidine who presented with a solitary rectal
      ulcer is reported. Initial biopsy was characteristic of extrapulmonary P carinii
      infection, with numerous organisms present. Occasional cytomegalovirus inclusion
      bodies were noted which may have been a copathogen but which were not treated.
      Treatment with intravenous pentamidine resulted in documented eradication of P
      carinii and complete resolution of the ulcer. Although lower gastrointestinal
      pneumocystosis has been described without ulceration, this is the first
      description of rectal ulceration presenting as the initial manifestation of
      extrapulmonary pneumocystosis.

PMID- 9193778
TI  - Colonoscopic findings in Crohn's disease--reproducible, but of questionable
      benefit.
AB  - Colonoscopy, a useful diagnostic tool in inflammatory bowel disease, is very
      accurate in detecting disease and assessing disease extent in Crohn's disease.
      Despite their accuracy, colonoscopic findings have not been routinely used in the
      objective follow-up of patients with Crohn's disease. The GETAID (Groupe d'etudes
      theraputic des affections inflammatoire du tube digestif) group has shown that
      following an intensive training period, endoscopists can describe colonoscopic
      findings in a reproducible manner. However, these descriptions poorly correlate
      both with clinical or laboratory indexes, and with short or medium term prognosis
      following prednisolone therapy.

PMID- 9193779
TI  - Welcoming remarks about the Janus phenomenon in science.

PMID- 9193780
TI  - Ethical and intellectual property in the biological sciences.
AB  - Ethical concerns on patents in the biological sciences are increased by the
      prospect of patents for higher life forms. A Canadian patent grants the owner the
      right to exclude others in Canada from making, using, or selling or offering for
      sale his or her invention for the term of the patent; however, it does not give
      the patent owner any positive rights to do likewise. As with other forms of
      property, the right to make, use, or sell a patented invention may be regulated
      by other laws or guidelines. In Canada, higher life forms, medical and surgical
      methods are not patentable subject matter. Unicellular life forms and subcellular
      material are considered patentable. Decisions on ethical issues are not
      considered by patent officers. The Patent Office is guided only by legislation.
      Other regulations by the legislatures can direct public policy and minimize
      risks.

PMID- 9193781
TI  - Ethics in matter of edition.
AB  - In this review are presented the different aspects and problems to which the
      edition of a journal like "Cellular and Molecular Biology" is submitted as well
      as all the incidences happening in the organization and editorial matter. There
      are presented the most frequent dysfunctions hampering the editorial and
      organisatorial activities, striking frontally all Ethical Rules and some of them
      constituting true criminal mafia activities from the side as well of authors and
      scientists as of a rival publishing company like Elsevier and of well established
      scientific organizations, like the IFCB and the CSBMCB, demonstrating as so far
      how lobbies exert inadmissible dictatorial pressures on the activity as well of
      individuals as of a journal like CMB and on a congress organization like our
      group, the Founders of the World Congresses of Cellular and Molecular Biology.
      Many examples are mentioned, most of them without indication of names and places
      for evident Ethical reasons but other ones with full names and places,
      particularly to obtain their condemnation by the Justice of particular countries
      and essentially by the High Court of the Human Rights for having used and for
      continuing to use mafiosi methods.

PMID- 9193782
TI  - Induction of humoral and cellular immune responses by vaccination with M.
      tuberculosis antigen 85 DNA.
AB  - DNA vaccines have been demonstrated to be effective in inducing protective cell
      mediated immune responses in animal models of infectious disease. In order to
      investigate this approach for potential use as a vaccine for tuberculosis, DNA
      constructs encoding Mycobacterium tuberculosis antigen 85A (Ag85A) were prepared.
      Expression of Ag85A in mammalian cells was demonstrated by transient transfection
      of cells in vitro. Intramuscular injection of Ag85A DNA vaccines resulted in the
      generation of anti-Ag85A antibodies and robust cell-mediated immune responses, as
      measured by lymphoproliferation of spleen cells in vitro upon specific antigen
      restimulation, leading to protection in animal challenge models. Therefore, the
      technique of DNA vaccination is effective in inducing relevant immune responses
      for protection against tuberculosis and may be used to identify the protective
      antigens of M. tuberculosis.

PMID- 9193783
TI  - Targeting of a G alpha subunit (Gi1 alpha) and c-Src tyrosine kinase to caveolae
      membranes: clarifying the role of N-myristoylation.
AB  - Many signaling molecules contain the consensus protein sequence Met-Gly at their
      N-termini that specifies N-myristoylation. Additionally, some of these proteins
      contain a cysteine at position-3 (Met-Gly-Cys) that can undergo palmitoylation.
      As many acylated proteins [G-protein subunits (alpha and beta gamma); c-Src and
      Src-family tyrosine kinases; H-Ras and Ras-related GTPases; endothelial nitric
      oxide synthase] are known to be targeted to caveolae membranes, it has been
      suggested that acylation is required or greatly facilitates this targeting event.
      However, it remains unclear whether myristoylation of Src-family kinases is
      necessary or sufficient for caveolar targeting. Our current study aims at
      clarifying the role of myristoylation in caveolar targeting using well
      characterized acylation mutants of two model proteins, namely Gi1 alpha and c
      Src. Here, we have used: i) detergent-free subcellular fractionation and ii)
      acylation mutants of Gi1 alpha and c-Src to systematically evaluate the relative
      contribution of myristoylation and palmitoylation to their caveolar targeting.
      Myristoylation (G2A) and palmitoytation (C3S) mutants of Gi1 alpha were poorly
      targeted to caveolae-enriched membrane fractions, while approximately 35% of
      total wild-type Gi1 alpha co-fractionated with caveolin, a caveolar marker
      protein. Similarly, a myristoylation minus mutant of c-Src was quantitatively
      excluded from caveolae. In contrast to a previous study, we conclude that
      myristoylation of Gi1 alpha and c-Src proteins is required for their correct
      caveolar targeting. However, the caveolar targeting of Gi1 alpha is dramatically
      augmented approximately 4-fold by palmitoylation. Our current studies are
      directly supported by the earlier in vivo observation that N-terminal
      myristoylation of v-Src is required for v-Src to phosphorylate caveolin on
      tyrosine residues in intact cells.

PMID- 9193785
TI  - Enhancement of human neutrophil survival and activation by TGF-beta 1.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional growth factor
      which promotes the inflammatory process. We have investigated the effect of TGF
      beta 1 on neutrophil survival, recruitment and activation. These last steps are
      essential for their participation in the inflammatory response. Our results
      demonstrate that TGF-beta 1 at a concentration of 20-40 ng/ml is a potent
      neutrophil chemotactic factor. The chemotactic activity induced by TGF-beta 1 is
      greater than that induced by fMLP (10(-8) M). Furthermore, TGF-beta 1 (20-30
      ng/ml) induces neutrophil activation demonstrated by an increase of respiratory
      burst and phagocytosis. Finally, TGF-beta 1 also enhances human neutrophil
      survival (43 to 93%) at concentrations as low as 2 to 20 ng/ml. This study
      provides evidence that TGF-beta 1 is capable of recruiting and activating
      neutrophils at inflammatory sites and enhances their survival.

PMID- 9193784
TI  - Secondary alcohol dehydrogenase as a marker of the conversion between
      progestagens and androgens in the rat testis.
AB  - Supraphysiological doses of LHRH-Analogue blocked the C21 to C19 steroid
      conversion in the mature Wistar rats testis. It was associated with inhibition of
      the NAD-dependent secondary alcohol-dehydrogenase (A-D II) histochemical reaction
      in the Leydig cells. Under this condition the treated group exhibited lower
      testis, seminal vesicle and prostate weights, intratesticular (IT) and plasmatic
      (PL) increased progesterone (P4) and decreased testosterone (T) concentrations.
      We also observed a decrease in the IT androstenedione (delta 4) concentration
      without pregnenolone (P5) change. All these data confirm a chemical castration
      pointing to a blockade at the level of the P450C21scc (17 alpha-hydroxylase/17-20
      desmolase) enzyme complex. After hCG administration there is no difference in
      sexual gland weights, while steroid's biosynthesis are stimulated and all IT and
      PL steroid concentrations increase. A-D II showed a lower optical density in the
      LHRH-A treated groups and no differences in the hCG rats. The hydroxylase or
      lyase activity of the P450C21scc may change under certain hormonal conditions as
      occurs in adrenarche, probably due to conformational changes in the active site
      of the enzyme system since it is encoded by only one gene. We suppose that the
      secondary alcohol itself and not the coenzyme reacts with the enzyme active site
      inhibited by the LHRH-A, since the NAD dependent 3 beta, hydroxysteroid
      dehydrogenase (3 beta HOST-D) is affected in the opposite sense. This study shows
      A-D II reaction as a marker of the mediated P450C21scc enzyme complex activity in
      the rat testis Leydig cells.

PMID- 9193786
TI  - Distribution of fiber types determined by in situ hybridization of myosin heavy
      chain mRNA and enzyme histochemistry in rat skeletal muscles.
AB  - We analyzed fiber types in rat skeletal muscles using a novel combination of in
      situ hybridization of myosin heavy chain (MyHC) mRNA, and enzyme histochemistry
      for succinate dehydrogenase (SD), which displayed metabolic properties. The fiber
      types were classified into the four major subtypes of I(beta/slow), IIA, IIX and
      IIB, and their intermediate types coexpressed two MyHC mRNAs: I and IIA, IIA and
      IIX, or IIX and IIB. The distribution of fiber types differed markedly in each
      skeletal muscle. The superficial region of limb muscles was composed mainly of
      fast-twitch fibers with oxidative-glycolytic and glycolytic activities, such as
      type IIX and type IIB. In contrast, the deep region was composed almost
      exclusively of type I and type IIA fibers both with oxidative activity. In this
      region, type IIA/IIX hybrid fibers were noted more frequently than type I/IIA and
      IIX/IIB hybrid fibers. In axial muscles, slow-twitch fibers and fast-twitch
      fibers composed predominantly of type IIB were distributed dispersively. The
      diaphragm and masseter showed a high proportion of type IIX and type IIB,
      respectively, to adapt to tissue-specific functional requirements and more
      frequently contained type IIX/IIB hybrid fibers than other observed muscles.

PMID- 9193788
TI  - New autoantibodies and their antigens in autoimmune diseases.
AB  - Autoimmune diseases are caused by failure to distinguish between host and foreign
      (e.g. microbial) antigens. We do not know why autoimmune disease occurs and what
      the relevant pathogenic mechanisms are. Autoantibodies might be considered as
      diagnostic markers, e.g. as "witnesses" to or "messengers" of autoimmune disease.
      Therefore, older and newer autoantibodies, as well as results on their respective
      antigens, will be considered.

PMID- 9193787
TI  - Soybean (Glycine max) agglutinin binds to corneal endothelial cells during wound
      repair and alters their microfilament pattern.
AB  - In the present study we have examined soybean (Glycine max) agglutinin (SBA)
      binding to cells of the rat corneal endothelium during wound repair. Circular
      transcorneal freeze injuries were given to the endothelia and the tissues were
      organ cultured at 37 degrees C in basal media Eagle with 10% serum for up to 72
      hrs. SBA failed to bind to the surface of non-injured corneal endothelium, but
      strongly bound to cells involved in the wound repair process. Punctate surface
      binding was detected 24 hrs. post-injury, but stronger binding was observed at 48
      hrs. after wounding. In this case, binding appeared to be distinctly distributed
      around the cell periphery. To investigate SBA binding during wound repair,
      endothelia were cultured in the presence of SBA (100 and 200 micrograms/ml). Cell
      migration into the wound area, and hence subsequent wound repair, was not
      affected at these concentrations. However, both concentrations altered cell
      morphology and microfilament patterns. Phalloidin staining of cells 24 hrs. after
      injury revealed that microfilaments appeared thinner and less in number. In
      addition, distinct aggregations of actin-positive material were detected at cell
      to-cell contacts. Cells around the tissue periphery do not partake in the repair
      process but displayed an SBA concentration dependent fragmentation of their
      circumferential microfilament bundles. At 48 hrs. post-injury, SBA-treated cells
      within the wound area, unlike their control counterparts, did not exhibit stress
      fibers. These results suggest that a SBA binding surface component is associated
      with the reorganization of actin during corneal endothelial wound repair, and
      that these cells can migrate across their natural basement membrane without the
      benefit of a highly organized microfilament cytoskeleton.

PMID- 9193789
TI  - Adenosine A3 receptor agonists inhibit murine macrophage tumor necrosis factor
      alpha production in vitro and in vivo.
AB  - Adenosine and related analogs have been shown to regulate a variety of cell
      functions through different classes of adenosine receptors. Murine J774.1
      macrophage cells were found to predominantly express adenosine A3 receptor RNA
      relative to adenosine A1 receptor or adenosine A2 receptor RNA. Adenosine
      receptor agonists, in a dose-dependent manner characteristic of the adenosine A3
      receptor, blocked endotoxin-induction of the TNF-alpha gene and TNF-alpha protein
      expression in the J774.1 macrophage cell line. The adenosine A3 receptor
      antagonist BW-1433 dose-dependently reversed this adenosine receptor agonist
      inhibitory effect on TNF-alpha gene expression. Thus, the binding of adenosine
      receptor agonists to the adenosine A3 receptor interrupts the endotoxin CD14
      receptor signal transduction pathway and blocks induction of cytokine TNF-alpha,
      revealing a novel cross-talk between the murine adenosine A3 receptor and the
      endotoxin CD14 receptor in J774.1 macrophages.

PMID- 9193790
TI  - Enhancement of DNA synthetic activity of thymic lymphocytes by the culture
      supernatant of thymus epithelial cells stimulated by growth hormone.
AB  - The authors examined the effect of the culture supernatant of growth hormone (GH)
      stimulated thymus epithelial cells (TECs) on DNA synthetic activity of thymic
      lymphocytes (TLs) and then examined TL proliferation-inducing factors released
      from the TECs. TEC line, IT-45R1 derived from Wistar strain rat, was used. It was
      revealed that the supernatant from TECs treated with GH enhanced significantly
      DNA synthetic activity of TLs and that the activity of the least dense subset of
      TLs, containing undifferentiated lymphoid cells and the most immature TLs, was
      significantly increased by the supernatant as compared with other subsets. Anti
      insulin like growth factor-I (IGF-I) monoclonal antibody (MAb) binding
      specifically to C region of IGF-I molecule was added to the culture supernatant
      from the GH-treated TECs, and then the supernatant was treated with
      ultrafiltration (MW cutting off; more than 50 kDa). When TLs were incubated with
      the ultrafiltered supernatant, the enhancement of TL proliferation induced by the
      supernatant of GH-treated TECs was significantly suppressed. However, the
      suppression did not descend to the level of TL-proliferative response observed in
      the supernatant of GH non-stimulated TECs. These results suggested that IGF-I
      released into the supernatant from GH-stimulated TECs enhances markedly the DNA
      synthetic activity of TLs and that the TL-proliferation-inducing factors (PIFs)
      other than IGF-I possibly exist in the supernatant of GH-stimulated TECs.

PMID- 9193791
TI  - Enhancement of thymic lymphocyte proliferation by the culture supernatant of
      thymus epithelial cells stimulated by prolactin.
AB  - Culture supernatant of thymus epithelial cells (TECs) stimulated by prolactin
      (PRL) enhanced markedly DNA synthetic activity of thymic lymphocytes (TLs) as
      compared with the hormone-non-stimulated TECs. The supernatant, which was treated
      with anti-insulin-like growth factor-I (IGF-I) monoclonal antibody (MAb) (binding
      specifically to C region of IGF-I) has still the capacity of enhancing remarkably
      TL-proliferation. However, further treatment by ultrafiltration of the MAb
      treated supernatant, removing the immune complex (IGF-I and anti-IGF-I MAb) from
      the supernatant, suppressed significantly the enhanced proliferation of TLs. It
      is assumed that PRL, like growth hormone (GH), promotes the release of IGF-I from
      TECs which induces a marked TL-proliferation. Moreover, it seems that the active
      site for inducing the proliferation is a region different from C, possibly the A
      or the B regions. TLs, present at different maturation steps, were separated into
      three subsets by discontinuous density gradient centrifugation and then treated
      with the supernatant of PRL-stimulated TECs. The least dense subset containing
      precursor T-cells and the most immature TLs showed the highest proliferative
      response to the supernatant in the comparison with other subsets and whole TLs.
      It is possible that the target cells to one of TL-proliferation-inducing factors
      (PIFs), namely IGF-I, in the supernatant exist in a greater concentration in the
      most immature step of TL population.

PMID- 9193792
TI  - Alkylglycosides as artificial primers for glycogen biosynthesis.
AB  - Glycogenin is a 37 kDa self-glycosylating protein which has been demonstrated to
      be the initiating enzyme and primer for glycogen biosynthesis in liver, skeletal
      muscle and other tissues. We have recently shown that glycogenin will use
      alkylglucosides and alkylmaltosides as artificial acceptors in glycosyl transfer
      from UDP-glucose and UDP-xylose in vitro and have suggested that such substrates
      might be used to promote the synthesis of glycogen in vitro and in vivo. We now
      report that alkylglycosides can also serve as acceptors for transfer of glucose
      by glycogen synthase, yielding alkylmaltooligosaccharide products which may
      potentially be elongated to glycogen. alpha-Glucosides were better substrates
      than the corresponding beta-glucosides, and alkylmaltosides were preferred over
      alkylglucosides. The hydrophobicity of the substrates markedly affected their
      acceptor activity, less hydrophobic substrates being more active. This is in
      contrast to the behavior of glycogenin, which acted preferentially upon the more
      hydrophobic substrates tested. Aromatic glycosides were also substrates for
      glycogen synthase, e.g., naphthyl-alpha-D- and beta-D-glucoside. The substrates
      were active in vitro both with partially purified rabbit muscle glycogen synthase
      and in incubations with crude muscle and liver homogenates from rat. In vivo
      experiments with mice further proved that intraperitoneal administration of
      alkylglucosides and alkylmaltosides increased the uptake of 14C-glucose in liver.
      The elevated uptake was due to an increase in both hydrophobic products, isolated
      by adsorption to Sep-Pak C18 columns, and more hydrophilic material that co
      fractionated with glycogen upon treatment of the tissue with alkali and
      precipitation with ethanol. These results demonstrate the ability of
      alkylglycosides to serve as artificial primers for glycogen biosynthesis in vivo.

PMID- 9193793
TI  - Male gonadal denervation by guanethidine at pre-puberty: different doses,
      different results. The intervention of the pineal deafferentation.
AB  - Since gonadal denervation and pineal deafferentation by cervical superior
      ganglionectomy affect sexual development, this study was performed to evaluate
      testicular steroidogenesis, spermatogenesis and the cervical superior ganglion
      (CSG) histology in rats treated with guanethidine (GD). The treatment was
      performed by GD s.c. injections for 3 weeks, from the 21st day of age to the 41st
      day of age (pre-puberty), when the animals were sacrificed. Different doses were
      used: group A = 10 mg/kg/day, group B = 50 mg/kg/day and saline (control group).
      Testicular denervation was confirmed by HPLC for catecholamines in testicular
      tissue. Testicular concentrations (TC) of progesterone (P4) and testosterone (T)
      were measured by RIA. Significantly higher TC of P4 and lower TC of T were
      observed only in group A in comparison with group B and the control group. No
      alteration of sperm production was observed in either treated group. Histological
      analysis of CSG showed only few neuronal alterations in group A rats, while in
      group B the nervous cells were practically destroyed. This suggests that 10
      mg/kg/day GD treatment probably produces a specific blockade of 17 alpha
      hydroxylase/17,20 desmolase at pre-puberty leading to a decrease of the androgen
      production. However, in the 50 mg/kg/day group no differences were observed
      concerning the steroid profiles, this result being attributed to the extensive
      damage to the CSG observed only in group B. The CSG destruction causes
      deafferentation of the pineal gland producing abolishment of the inhibition of
      the 17 alpha-hydroxylase/17,20 desmolase promoted by melatonin or by an out of
      phase production of androgen.

PMID- 9193794
TI  - Immunotherapy of metastases with lymphocytes treated with exogenous RNA in mice
      bearing B16 melanoma.
AB  - Subline B16-F10, a variant cell line of B16 melanoma, is highly metastatic to the
      lung when injected intravenously into C57BL/6 mice. This experimental metastasis
      model was used to test the anti-tumor effect of exogenous RNA extracted from the
      lymphoid organs of immunized animals with B16-F10 cells. This RNA preparation is
      referred to as B16-RNA. Adoptive immunotherapy with lymphocytes treated with B16
      RNA was effective in reducing significantly the number of pulmonary metastatic
      nodules. Lymphocytes incubated with medium alone or with RNA from non-immunized
      animals (N-RNA) were used as controls. The ability of B16-RNA in modulating
      antimetastatic activity of normal lymphocytes is abolished by hydrolysis with
      KOH. This finding indicates that the integrity of the polynucleotide chain is
      essential for the activity of B16-RNA. The anti-tumor effect of lymphocytes
      treated with B16-RNA was enhanced by incubation with a low dose of interleukin-2
      (IL-2). A possible role of the double-stranded RNA dependent protein kinase in
      this phenomenon is discussed.

PMID- 9193795
TI  - In vitro organogenesis and transgenosis aspects in globe artichoke (Cynara
      scolymus L.).
AB  - The genetic transformation of globe artichoke (Cynara scolymus L.) cells is
      possible. However, the percentage of transformed cells is still low and the
      regeneration process appeared to be the critical step towards the obtention of
      transgenic plants. The present work reports the organogenesis potentialities from
      new vegetal materials: cotyledons and leaves from in vitro artichoke plants. The
      results showed that cotyledons gave better rates of neoformation than leaves and
      this was reached in a shorter time. Regarding the transfer of genetic resistance
      to globe artichoke, a model system was developed using Nicotiana benthamiana as
      systemic host for artichoke viral diseases. Mutagenized sequences of the
      replicase gene of artichoke motteled crinckle virus (AMCV) as transferable
      genetic material for resistance induction were performed. Transgenic lines of
      Nicotiana benthamiana were obtained and some of them presented a considerable
      attenuation of symptoms when challenged with AMCV.

PMID- 9193796
TI  - Ovarian granulosa and theca interstitial cells: a morphological and physiological
      analysis in guanethidine denervated rats at pre-puberty.
AB  - Since ovary denervation causes delayed puberty, we investigated the relative
      importance of ovary innervation on the morphology and physiology of theca
      interstitial cells (TIC) and granulosa cells (GC) in female rats at pre-puberty.
      Elimination of the sympathetic innervation was performed by long term post natal
      treatment with guanethidine (GD), an adrenergic blocking agent. The
      sympathectomized rats exhibited: reductions in follicular volume (40%), granulosa
      cells area (43%) and theca interstitial cell volume (50%). Ovarian concentrations
      of pregnenolone (P5) and progesterone (P4) were decreased whereas no differences
      were observed in androstenedione (A) and estradiol (E2). The intensity of the
      immunocytochemical reaction for 3 beta hydroxysteroid dehydrogenase (3 beta-HSD)
      detected only in interstitial cells, did not show any difference. These in vivo
      results include the TIC in the bulk of ovarian structures affected by GD
      denervation at pre-puberty as it was already observed for GC. The reduced
      area/volume occupied by these cells in the GD treated ovary is associated to a
      blockade of the initial steps of the steroidogenic pathway, probably at the level
      of the cholesterol side chain cleavage enzyme (P450 s.c.c.), previously to P5
      synthesis, since P5 is reduced. Similar intra ovarian concentrations of androgens
      are discussed in terms of possible pineal deafferentation promoted by GD at high
      doses.

PMID- 9193797
TI  - Dual messenger function for prostaglandin E2 (PGE2) in human placenta.
AB  - There is periparturitional increase of prostaglandin E2 (PGE2) in the plasma and
      amniotic fluid of humans. PGE2 increases uterine contractions and also increases
      uterine blood flow to sustain the contractions. A question arises as to what role
      PGE2 plays in human placental circulation. It may regulate feto-placental blood
      flow and closure of placental resistance vessels at parturition. Therefore, we
      have investigated (a) the release of PGE2 into fetal and maternal circulations,
      and (b) the influence of PGE2 on the feto-placental pressure in the isolated
      perfused cotyledon of normal human term placenta. The placental cotyledon was
      perfused with aerated. (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4,
      37 degrees C) containing 2% albumin on both maternal (230 ml, 12 ml/min., 0.6"
      Hg) and fetal (93 ml, 1.75 ml/min., 1.75" Hg) sides in a closed recirculating
      system. In one group of cotyledons, perfusion samples (2 ml) were collected at
      regular intervals from both perfusates for 3 hrs. and PGE2 was determined in
      aliquots (0.5 ml) of samples by a specific radioimmunoassay. In a second set of
      cotyledons, exogenous PGE2 was administered into fetal perfusate, and pressure
      was monitored as a function of time. These experiments gave the following
      results: 1) During the initial 20 min., a constant level of PGE2 (2.3-4.4 pg/ml)
      was maintained in both perfusates. At 3 hrs., the concentrations increased to
      about 110 ng/ml on the fetal side and 30 ng/ml on the maternal side. The total
      amount of PGE2 accumulated in the fetal and maternal reservoirs reached to 10.16
      and 7.03 ng, respectively. 2) PGE2 (10-150 ng/ml) increased the feto-placental
      perfusion pressure in a concentration dependent manner. At 150 ng/ml, the
      pressure increased to 125-240% of control pressure observed at the beginning of
      the experiment. These studies suggest that a) placental trophoblast has the
      capacity for the synthesis and release of PGE2 into fetal and maternal
      circulations; b) PGE2 exhibits differential effects in the placental and uterine
      blood vessels, vaso-constriction in placental vessels and vasodilation in uterine
      blood vessels, and (c) PGE2 exhibits dual effects on blood vessels possibly by
      activating two different subtypes of PG-receptors.

PMID- 9193798
TI  - Midkine stimulates Wilms' tumor cell proliferation via its signaling receptor.
AB  - Midkine, but not pleiotrophin, is mitogenic to human Wilms' tumor cells (G401
      line) in dose-dependent and time-dependent fashion. Midkine specifically binds to
      high affinity (Kd = 0.15 +/- 0.02 nM, 210 kDa) and low affinity receptors (Kd =
      0.65 +/- 0.07 nM, 75 kDa) on G401 cell surface, that has been confirmed by cross
      linking and competition experiments. In addition, midkine stimulates a tyrosine
      phosphorylation of several proteins with molecular weight about 110-115 kDa, 130
      140 kDa and 210 kDa. These data allow us to suggest that a key point in
      stimulation of G401 cell proliferation is interaction of midkine to its signaling
      receptor.

PMID- 9193800
TI  - Controlling elements in replication of the human immunodeficiency virus type 1.
AB  - We have reviewed the genetic structure of HIV-1 from the perspective of
      understanding viral and cellular regulatory factors that affect viral
      replication. Comparisons are drawn, as appropriate, with other human
      retroviruses, such as HIV-2, in regard to our understanding of pathogenesis. The
      synthesis of viral protein and the manner in which viral assembly takes place is
      also discussed.

PMID- 9193799
TI  - Expression of the alpha 7 subunit of the nicotinic acetylcholine receptor in
      normal and myasthenic human thymuses.
AB  - The nicotinic acetylcholine receptor (AChR) is a transmembrane glycoprotein
      composed of five homologous subunits. Different isoforms of the AChR alpha
      subunit exist (alpha 1 to alpha 9). Of them, alpha 1 is expressed in muscle,
      alpha 2 to alpha 9 in neuronal cells. Muscle AChR is the target autoantigen in
      the autoimmune disease myasthenia gravis (MG). The thymus is implicated in MG
      pathogenesis, and the anti-AChR autoimmune response may start in this tissue,
      that expresses the muscle-type alpha 1 subunit as well as other muscle AChR
      subunits. The thymus also expresses the "neuronal" alpha 3 and alpha 5 subunits.
      By using polymerase chain reaction and other molecular techniques, we demonstrate
      here expression of the AChR alpha 7 subunit transcript in thymuses from both
      myasthenic patients and normal subjects. The alpha 7 subunit can form homo
      oligomeric functional AChR complexes that, like muscle AChR, bind alpha
      bungarotoxin. The demonstration of expression of the alpha 7 subunit in the
      thymus suggests that alpha-bungarotoxin binding, functional AChRs of the neuronal
      type are normally present in the thymus.

PMID- 9193801
TI  - The role of integrins and extracellular matrix in anchorage-independent growth of
      a mammary carcinoma cell line.
AB  - Anchorage-independent growth is a property of malignant cells. Extracellular
      matrix proteins are present in tumor spheroids but their function is not clearly
      defined. In this paper we show that a murine mammary carcinoma cell line, SP1,
      which expresses the fibronectin receptor alpha 5 beta 1 requires fibronectin for
      anchorage-independent growth in soft agar. Growth factors (hepatocyte growth
      factor and transforming growth factor-beta) also promote SP1 colony growth. In
      contrast, collagen types I and IV have an inhibitory effect on SP1 colony growth.
      A clone isolated from SP1 cells which expresses the collagen/laminin receptor
      alpha 2 beta 1 as well as the fibronectin receptor alpha 5 beta 1, demonstrates
      increased colony formation in the presence of fibronectin and collagen. These
      data suggest a role for both the alpha 5 beta 1 and alpha 2 beta 1 integrin
      receptors in the regulation of anchorage-independent growth of mammary carcinoma
      cells.

PMID- 9193802
TI  - Scintigraphic evaluation of obstructing primary megaureter with Tc-99m MAG3.
AB  - Two children with the antenatal diagnosis of hydronephrosis secondary to a
      primary obstructed megaureter are presented. Both children were treated
      nonoperatively. They were observed with serial diuretic scintigrams using Tc-99m
      MAG3 and renal sonography. Throughout, the children have been asymptomatic.
      During a 3-year follow-up period, the diuretic renogram documented resolution of
      obstruction in one child and stable renal function with improved drainage in the
      other.

PMID- 9193803
TI  - Relative sensitivity of Tc-99m WBC versus In-111 WBC in a patient with Crohn's
      disease on steroids.
AB  - Numerous studies have shown that chemotaxis is affected by certain antibiotics
      and steroids. A patient had Crohn's disease in relapse with multiple small bowel
      fistulae and mesenteric abscesses. Although the Tc-99m WBC scan did not show the
      intra-abdominal inflammatory foci, an In-111 WBC scan performed within a week
      delineated the abscesses and these were later confirmed at surgery. This case is
      being presented not only to show the relative sensitivities of a Tc-99m WBC vs.
      an In-111 WBC scan, but also to discuss the impediment to polymorphonuclear
      leukocyte chemotaxis by steroids, which may be a contributory factor to the
      sensitivities of the different radiopharmaceuticals selected for detection of
      intra-abdominal septic foci.

PMID- 9193804
TI  - Cerebral perfusion SPECT imaging in epileptic and nonepileptic seizures.
AB  - Patients with epileptic and nonepileptic seizures are commonly encountered in
      clinical practice, and they can pose a difficult diagnostic problem. We present
      two cases that show the difficult task of differentiating between true epileptic
      and nonepileptic or psychogenic seizures in some patients. The clinical
      presentations were complex and the use of video-monitored EEG alone was
      insufficient to make definitive diagnoses. Ictal and interictal Tc-99m HMPAO
      brain perfusion SPECT imaging examinations were used to help establish the
      correct diagnoses. This report describes the advantage of using the brain
      perfusion SPECT imaging examination. The injection of stabilized Tc-99m HMPAO
      during an ictal event followed by appropriate medical therapy provides a method
      of obtaining a reasonable image of relative perfusion (activity) during the
      seizure. These images can then be compared with interictal examinations and an
      epileptic or nonepileptic focus may be localized. The Tc-99m HMPAO brain
      perfusion SPECT imaging study was helpful in establishing the correct diagnosis
      in both cases.

PMID- 9193805
TI  - Reduced radioactivity in the periphery of the liver in a patient with idiopathic
      portal hypertension.
AB  - The authors report a case of idiopathic portal hypertension in which
      radioaccumulation in the peripheral region of the liver decreased markedly. On
      dynamic CT, peripheral regional enhancement of the liver was seen in the arterial
      phase. The region was hypointense on T1-weighted MR images and hyperintense on T2
      weighted images. On portograms via the superior mesenteric artery, markedly
      decreased portal venous perfusion was seen in the peripheral region of the liver.
      Tc-99m galactosyl human serum albumin (GSA) liver scintigrams showed decreased
      accumulation in the peripheral region and unchanged accumulation in the central
      region of the liver. Tc-99m GSA liver scintigraphy clearly showed localized liver
      dysfunction in the peripheral region.

PMID- 9193806
TI  - The use of three-phase scintigraphy for diagnosing hemangiomas of the
      extremities. A clinical evaluation.
AB  - Five hemangiomas were found in four patients and were assessed by three-phase
      blood perfusion and blood-pool scintigraphy to determine the usefulness of this
      method for the imaging characteristics of different types of hemangiomas of the
      extremities. After injecting Tc-99m RBC or Tc-99m DTPA HSA, dynamic perfusion and
      early and delayed pool images were obtained and analyzed. The perfusion images of
      one cavernous hemangioma and two venous hemangiomas showed normal activity, but
      blood-pool imaging showed increased activity, whereas on perfusion imaging and
      early blood-pool imaging, another cavernous hemangioma showed a partial increase
      in activity in its periphery and on delayed blood-pool imaging, diffuse increase
      in activity. Further, the remaining hemangioma, a mixed-type hemangioma, showed,
      diffuse increase in activity on both perfusion and blood-pool imaging. Thus,
      three-phase scintigraphy was found useful in evaluating and achieving a diagnosis
      of a hemangioma of the extremities.

PMID- 9193807
TI  - Cardiopulmonary thromboembolism detected by Tc-99m MH-1 antifibrin antibody.
AB  - A patient with shortness of breath had a high probability lung scan for pulmonary
      embolism, but no obvious embolic source. Whole-body scintigraphy using Tc-99m
      labeled Fab' antifibrin monoclonal antibody showed large central pulmonary emboli
      as well as tracer uptake in the right atrium and aortic arch. No lower extremity
      clot was detected. This case shows significant differences in the appearance of
      pulmonary embolism as assessed by direct clot and ventilation-perfusion
      scintigraphy. It shows the importance of the heart as the origin of pulmonary
      emboli and the utility of direct thrombus visualization.

PMID- 9193808
TI  - Unusual false-positive radioiodine whole-body scans in patients with
      differentiated thyroid carcinoma.
AB  - Radioiodine whole-body imaging is the most accurate method in the diagnosis of
      metastases from differentiated thyroid cancer. However, false-positive images
      rarely occur. The authors report unusual cases of thymic hyperplasia and post
      traumatic skull changes mimicking mediastinal, skull, or cerebral metastases.
      Nonthyroidal causes were diagnosed by other radionuclide studies (bone and brain
      scintigraphy) and CT scans. Follow-up and undetectable thyroglobulin levels
      helped confirm the benign cause.

PMID- 9193809
TI  - Giant diverticulum of urinary bladder causing bilateral hydronephrosis in an
      adult. Diagnostic features on radionuclide scintigraphy.
AB  - A 24-year-old man with congenital bladder diverticula leading to bilateral
      hydronephrosis diagnosed on radionuclide scintigraphy is described. Diagnostic
      findings of sonogram and CT scan are also mentioned.

PMID- 9193810
TI  - Rim sign. Radionuclide imaging in a patient with acute gangrenous cholecystitis
      and cholelithiasis after nonspecific abdominal ultrasonography.

PMID- 9193811
TI  - Chronic CSF leak into the peritoneal cavity shown by radionuclide cisternography.
      Successful treatment with an epidural blood patch.

PMID- 9193812
TI  - Ga-67 muscle uptake in a weight lifter after exercise.

PMID- 9193813
TI  - Renal scintigraphic findings in a patient with hydrometrocolpos.

PMID- 9193814
TI  - Incidental detection of pulmonary infection during the evaluation of protein
      losing enteropathy with In-111 transferrin.

PMID- 9193815
TI  - Crossed cerebellar hypoperfusion in mesencephalic infarcts.

PMID- 9193816
TI  - Tc-99m MAG3 renal transplant imaging of scrotal urinoma.

PMID- 9193817
TI  - Ga-67 uptake in a case of tuberculous spondylitis.

PMID- 9193818
TI  - Systemic-portal shunt in unilateral iliac vein stenosis.

PMID- 9193819
TI  - Evaluation of a patient with a brain abscess caused by nocardia asteroides
      infection with Ga-67 and Tc-99m HMPAO leukocytes.

PMID- 9193821
TI  - Polyostotic fibrous dysplasia in McCune-Albright syndrome diagnosed by bone
      scintigraphy.

PMID- 9193820
TI  - Demonstration of subclinical inguinal hernia by peritoneal scintigraphy.

PMID- 9193822
TI  - Double-phase scanning of the thyroid gland with Tc-99m MIBI in a patient with a
      malignant nodule. A case of tracer redistribution?

PMID- 9193823
TI  - Ga-67 visualizing metastases of malignant melanoma to gastric cancer.

PMID- 9193824
TI  - Incidental massive Ga-67 uptake in the thorax and abdomen for the diagnosis of
      lumbar osteomyelitis.

PMID- 9193825
TI  - Scintigraphic 'eyebrow sign' on bone scan.

PMID- 9193826
TI  - An unusual perfusion pattern of hepatic metastases.

PMID- 9193828
TI  - Coronary artery fistula.

PMID- 9193827
TI  - False-positive WBC imaging secondary to a distended bladder and fecal retention.

PMID- 9193829
TI  - TI-201 chloride and Tc-99m ECD brain SPECT in lymphoma with and without massive
      necrosis.

PMID- 9193830
TI  - Esophageal cancer detection with Tc-99m tetrofosmin SPECT.

PMID- 9193832
TI  - Comparison of F-18 FDG to I-123 and I-131 scans in thyroid carcinoma.

PMID- 9193831
TI  - Survey of myeloblastoma with Ga-67 scan in a patient with acute leukemia.

PMID- 9193833
TI  - Scintigraphic evaluation of metastatic osteosarcoma. The importance of SPECT bone
      scintigraphy and correlative imaging.

PMID- 9193834
TI  - Positron emission tomography in the diagnosis of variant angina.

PMID- 9193835
TI  - Prognostic factors and early resumption of cyclosporin A in renal allograft
      recipients with thrombotic microangiopathy and hemolytic uremic syndrome.
AB  - Biopsy-proven thrombotic microangiopathy (TMA) was found in 22 of 436 (5%) renal
      transplant recipients, with similar incidence in recipients of cadaver or living
      related allografts. All patients with TMA presented different degrees of severity
      of the hemolytic uremic syndrome (HUS). Prognosis was poor when HUS occurred
      shortly after transplant in recipients of cadaveric kidneys (55% graft loss). It
      was more favorable when HUS occurred later in the post-transplant course or in
      recipients with allografts from living related donors, irrespective of time of
      occurrence. Other factors such as extent of TMA, degree of thrombocytopenia,
      hemolysis or renal dysfunction were not predictive of graft loss. Cyclosporine
      was resumed in 14 of 16 recipients shortly after clinical recovery without
      recurrence of HUS. In conclusion, HUS carries poor prognosis when occurring
      shortly after transplant in cadaver kidney recipients. Once the graft function
      improves, cyclosporine can be safely resumed.

PMID- 9193836
TI  - Primary shunt perfusion detected by colour flow Doppler imaging and its impact on
      liver allograft survival.
AB  - Primary dysfunction (PDF) and eventual primary nonfunction (PNF) of liver
      allografts have been characterized by various clinical and laboratory parameters
      reflecting graft function, cellular integrity and extrahepatic influence
      following orthotopic liver transplantation (OLT). During the past 6 yr we have
      been able to demonstrate that this potentially devastating condition is routinely
      accompanied by a pathological initial perfusion pattern detected by colour flow
      doppler imaging (CFDI) within hours following OLT. In the majority of PDF cases
      (n = 30) CFDI revealed increased vascular resistance in regard to arterial blood
      flow to the malfunctioning graft, with a resulting 1-yr graft survival rate of
      80% following the institution of early prostaglandin therapy in this group of
      patients. A completely different perfusion pattern was noticed by CFDI in a total
      of 13 cases with grossly decreased arterial resistance, resulting in an
      apparently supranormal arterial blood supply together with a reduced portal
      inflow in comparison to primarily functioning grafts. The presence of this
      pathologic graft perfusion was explained by the formation of arterio-portal
      shunts within the graft during conservation and reperfusion, leading to a 1-yr
      graft survival of merely 46.1%.

PMID- 9193837
TI  - A randomized controlled trial of pentoxifylline for the prevention of delayed
      graft function in cadaveric kidney graft.
AB  - Ischemia/reperfusion has been implicated in the mechanism of delayed graft
      function (DGF). Pentoxifylline (PTX) has been shown to suppress TNF alpha
      (released by activated macrophages, inhibiting subsequent superoxide anion
      release from neutrophil activation. In addition, PTX decreases cyclosporine (CsA)
      induced renal endothelial release and vasoconstriction. Thus, administration of
      PTX to renal transplant patient could be an excellent approach to prevent DGF and
      vascular toxicity of CsA in the early graft period. One hundred-and-forty
      consecutive patients receiving cadaveric kidney transplantation were registered
      in a randomized double-blind study comparing PTX vs. a placebo. PTX had no
      demonstrable effect on the incidence of DGF, on the rapidity of the renal
      function recovery, and on the ability to use higher doses of CsA in the first
      month post-graft.

PMID- 9193838
TI  - Allograft infiltrating cytotoxic T lymphocytes recognize kidney-specific human
      minor histocompatibility antigens.
AB  - The role of minor histocompatibility antigens (mH) in allograft immunity has been
      proposed, but the nature of these antigens and their immunogenicity are not well
      understood. We have shown that tissue-specific cytolytic T lymphocytes (CTL) can
      be isolated form graft infiltrating lymphocyte (GIL) populations from renal
      transplant recipients undergoing acute cellular rejection. In most cases these
      CTL were allorestricted recognizing donor mismatched kidney MHC class I antigens.
      In contrast, one patient's GIL T cells demonstrated specific lytic activity
      against HLA-B35 expressed on primary kidney epithelial cell lines (KCL) but not
      on B-lymphoblastoid cell lines (LCL). Since HLA-B35 was a shared antigen between
      donor and recipient, these results suggest that CTL within the GIL population are
      recognizing a tissue-specific minor histocompatibility antigen presented in the
      context of self-HLA-B35.

PMID- 9193839
TI  - Highly successful long-term outcome of kidney transplantation in Chinese
      recipients: an enhancing race effect?
AB  - We report on 352 cadaveric kidney transplants and 294 living related transplants
      performed over a 25-yr period among the Chinese population of Hong Kong. There is
      a marked preference for transplanting male patients, especially from living
      donors, and we argue that this represents a cultural phenomenon within the
      Chinese population. The 10-yr graft survivals for related and cadaveric
      transplants are 86.2% and 67.4%, respectively. These figures are appreciably
      higher than corresponding figures in Caucasian populations. We show beneficial
      effects of using cyclosporin A, minimizing the cold ischemia time and avoiding
      very young and very old donors. There is a clear benefit of transplanting kidneys
      with zero or one mismatched HLA antigen against the recipient but no stepwise
      decrease in outcome as the number of mismatched antigens increases. There is
      close concordance between the outcome of living related grafts with zero, one,
      and two mismatched haplotypes against the recipient and no observable benefit of
      haplotype matching. We show that Chinese renal transplant recipients in other
      centers also have better long-term graft outcome than Caucasians, both for
      cadaveric and living related transplants. We draw attention to the existence of a
      detrimental "race effect" in other studies when Black recipients are compared
      with Caucasians and consider whether an enhancing race effect exists for Chinese
      or whether the better outcome reflects different underlying diseases in Chinese.

PMID- 9193840
TI  - Sequential biological immunosuppression. Induction therapy with rabbit
      antithymocyte globulin.
AB  - This paper describes 108 consecutively treated patients receiving 109 cadaveric
      (CD) and living donor (LD) renal allografts using a protocol of quadruple
      sequential immunosuppression with a rabbit anti-human thymocyte IgG
      (Thymoglobuline), azathioprine, tapering corticosteroids, and delayed
      introduction of cyclosporine A. The average length of induction was 6.1 d with an
      average Thymoglobuline dose of 2.0 mg/kg/d. The mean serum creatinine pre
      transplant of the cohort was 877 +/- 263 (sd) mumol/L, 146 +/- 44 mumol/L by 3
      months post-transplant, and 136 +/- 40 mumol/L at 1 yr. The overall 4-yr
      actuarial patient survival was 96.6%, and allograft survival was 88.6% at 2 yr
      and 83.6% at 4 yr. The incidence of acute rejection episodes defined by intention
      to treat was 32%. Additionally, eight patients in this series received
      retreatment with Thymoglobuline for a first acute rejection, and only one of
      these had a second rejection. This was in contrast to 5/11 recurrent rejections
      following steroid treatment only, and 5/13 recurrences following OKT3 treatment
      for the first rejection episode. The side-effect profile of Thymoglobuline was
      largely benign, and the biological agent was well tolerated with initial fever in
      75%, chills in 27%, and leucopenia in 22% of the patients. All other drug-related
      adverse events had a prevalence of less than 3%, and clinical signs of
      meningismus were seen in only one patient. There were five associated episodes of
      CMV. We conclude that Thymoglobuline as part of a quadruple sequential
      immunosuppressive regimen for renal transplantation is well tolerated and can be
      associated with a good short- and long-term outcome of renal transplantation.

PMID- 9193841
TI  - Development of microchimerism in pediatric patients after living-related liver
      transplantation.
AB  - Microchimerism has been suggested to play an important role in the long-term
      acceptance of allogeneic organ grafts by transplant patients and for the
      maintenance of a state of donor-specific low responsiveness. In order to
      elucidate the kinetics of the development of chimerism we have performed a follow
      up analysis in 10 pediatric patients with living-related liver transplantation
      (LRLTx). Blood samples obtained during the first 6 months and at 18 months post
      transplant and skin biopsies taken at one month were analysed for the presence of
      donor cells by PCR using donor-specific HLA-DRB1 primer pairs or primers for a Y
      chromosome-specific sequence. Furthermore 13 long-term patients more than 2 yr
      after LRLTx were studied at two different time points. In the follow-up studies
      donor cells could be demonstrated in the blood of all patients immediately after
      transplantation. After a gradual decline all patients became chimerism-negative
      for several weeks or months. At 6 months, however, in five of eight patients
      tested and at 18 months in six of nine patients donor cells had reappeared. This
      biphasic pattern in the development of chimerism is proposed to reflect the
      occurrence of different donor-derived cell populations in the recipient. The
      population giving rise to the first wave of chimerism probably represents matured
      cells with a limited lifespan which are released from the graft into the
      circulation of the recipient during the first weeks after transplantation. The
      population of cells occurring with the second wave of chimerism is likely to have
      been generated by donor-derived cells with stem cell potential located either in
      the graft or in the hematopoetic organs of the recipient after emigration from
      the graft. This model may be able to explain fluctuations in the incidence and
      degree of microchimerism described in other patient populations during the first
      year post-transplant. Of the 13 long-term patients, chimerism could be
      demonstrated in 11. In seven patients it was detected in both blood and skin, in
      three patients the results obtained for blood and skin were discordant. In one
      patient only blood was analysed. It is not clear whether the negative results
      really reflected the absence of chimerism or whether the number of donor cells
      was below the level of detectability.

PMID- 9193842
TI  - Drainage of the exocrine pancreas in clinical transplantation: comparison of
      bladder versus enteric drainage in a consecutive series.
AB  - The purpose of this study was to define the incidence of urologic and metabolic
      complications after simultaneous kidney/pancreas transplantation (SKPT) with
      bladder drainage (BD). Review of 55 SKPT with BD performed between 1989 and 1995
      demonstrated patient, kidney, and pancreas survival rates of 95%, 89%, and 78%,
      respectively, with a mean follow-up of 41 months (range 12-78 months). Over this
      follow-up period 78% of these patients experienced a urinary tract infection, 27%
      had hematuria, and 38% had at least one hospital admission for dehydration.
      Recent experience with primary enteric drainage of the exocrine secretions of the
      transplanted pancreas (n = 11) has demonstrated the total absence of these
      complications (follow-up range 2-12 months). These results suggest the value of
      continuous re-evaluation of surgical techniques as the care of transplant
      patients evolve.

PMID- 9193843
TI  - Clostridial infection of a liver transplant treated with retransplantation.
AB  - Clostridial infection of a liver transplant is reported and was treated
      successfully with immediate retransplantation and antibiotics. This strategy may
      salvage patients who otherwise have a fulminant course and certain death. This
      case supports the general principle that infection localized to the liver can be
      successfully treated with retransplantation when appropriate.

PMID- 9193844
TI  - Three-dimensional helical computed tomographic cholangiography: application to
      living related hepatic transplantation.
AB  - Variations in the anatomy of intrahepatic bile ducts complicate operations in
      living related hepatic transplantation (LRHT). Preoperative delineation of the
      biliary system is important to achieve successful results. The purpose of this
      study was to assess the utility and accuracy of three-dimensional helical
      computed tomographic cholangiography (3DHCTC) as a replacement for endoscopic
      retrograde cholangiography (ERC) in evaluating the anatomy of the intersegmental
      biliary connection of the potential donors in LRHT. Helical CT was performed in
      16 potential donors after a slow infusion of 100 cm3 meglumine iodipamide. By
      using the maximum intensity projection and shaded surface displaced image
      reconstruction technique, three-dimensional images of the bile ducts were
      isolated from the surrounding hepatic parenchyma. Among the 16 potential donors,
      3 cases underwent an ERC study and another 7 cases donated liver graft during
      LRHT. In all 16 cases the anatomy of the bilateral essential intrahepatic ducts
      was well displayed with and without the liver parenchyma background in an axial
      and three-dimensional fashion which had good correlation with images from ERC and
      intra-operative cholangiography. Two variants were found, including drainage of
      the right posterior intrahepatic duct into the left hepatic duct and direct
      drainage of the segment II bile duct into the common hepatic duct, respectively.
      It is concluded that unusual routes of intrahepatic ducts may necessitate a
      change in the cutting plane during graft retrieval and patterns of ductoenteral
      anastomosis to avoid potential complications to both donors and recipients. With
      the advantages of non-invasiveness and comparable accuracy in demonstrating
      biliary anatomy, 3DHCTC may replace the traditional ERC in the pre-transplant
      survey of potential donors for LRHT.

PMID- 9193845
TI  - Regional vs. national renal sharing organizations: pros and cons.
AB  - Delayed graft function, defined as the need of dialysis in the first week after
      transplantation, neither due to immunological nor technical causes, determines a
      poor outcome of renal grafts. Delayed graft function is related to the cold
      ischemia time, which is shorter in local allocation programs. These, however, do
      not assure an optimal HLA-A,B,DR matching that can be provided by national
      allocation organizations. We reviewed 160 cadaveric kidney grafts performed in
      our local transplant network. Owing to the long waiting list caused by organ
      shortage, we were able to ensure both a high-grade histocompatibility and short
      cold ischemia times. The mean HLA-B,DR mismatch was 1.17. Cold ischemia time was
      < 24 h in 85% of cases. The incidence of DGF was 23.1%. In our experience a
      regional sharing program in the case of organ shortage provides good graft
      outcome (86.9% graft survival at 1 yr) with low incidence of delayed graft
      function.

PMID- 9193846
TI  - Liver transplantation: treatment of choice for hepatic and neurological
      manifestation of Wilson's disease.
AB  - Liver transplantation (LTX) is an approved method to treat patients with end
      stage liver cirrhosis and acute liver failure due to Wilson's disease. Initially,
      there was some consideration about the indication for LTX in the case of Wilson's
      disease with severe neurological impairment but normal liver function. From 1988
      until 1995, 13 out of 700 LTX (1.9%) were performed for Wilson's disease.
      Indications for LTX were (I) intractable neurological impairment with normal
      liver function (n = 4; including one patient with Child A cirrhosis), (II)
      fulminant hepatic failure (n = 3), and (III) end-stage liver cirrhosis (n = 6)
      (Child B, n = 1; Child C, n = 5). There were 8 females and 5 males with a mean
      age of 27 yr (range 15-34 yr). All patients of group I required continuous
      nursing care before LTX, in spite of pretreatment with d-penicillamine and zinc.
      The most frequent symptoms in these patients were dysphagia (n = 4), dysarthria
      (n = 4), tremor (n = 4), sialorrhea (n = 3), ataxia (n = 3), dystonia (n = 3) and
      handwriting difficulties (n = 3). All patients of group II presented with
      hemolytic anemia. The survival rate was 100%, and all patients were doing well
      after a mean follow-up period of 32.8 months (range 8-68 months). The
      postoperative course was without severe infectious and other complications. All
      patients of group I revealed the first signs of improvement for all types of
      neurological symptoms 4-6 wk after LTX. One patient has been without any symptoms
      from 18 months until 5.5 yr after LTX. Two patients with short-term follow-up
      also had noticeable improvement of neurological impairment, but residual symptoms
      are still present. One patient showed only slight improvement. We conclude that
      Wilson's disease may be a good indication for LTX for both neurological
      manifestation with stable liver function and hepatic manifestation with cirrhosis
      or acute liver failure.

PMID- 9193847
TI  - Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney
      transplant recipients.
AB  - After allogenic transplantations a dramatic increase in the development of
      arteriosclerotic plaques can be observed, which might be due to metabolic
      alterations, influenced by changes of the transplant organ or immunosuppression.
      In this study the effects of FK 506 in kidney transplant patients on
      cardiovascular risk factors were compared to cyclosporin A (CsA)
      immunosuppression. Both groups showed no statistical differences in number,
      kidney function, age, body weight, sex distribution, steroid dosage and follow-up
      time after transplantation. Total cholesterol was similar in FK 506-treated
      patients (231 +/- 22 vs. 278 +/- 52 mg/dl) as compared with patients with CsA
      immunosuppression. Furthermore, there were no differences in triglycerides (220
      +/- 72 vs. 210 +/- 67 mg/dl), HDL-cholesterol (67 +/- 14 vs. 52 +/- 18 mg/dl) and
      fasting glucose (112 +/- 36 vs. 116 +/- 17 mg/dl). However, the concentration of
      LDL-cholesterol (114 +/- 21 vs. 167 +/- 37 mg/dl), the independent risk factor
      Lp(a) (11 +/- 9 vs. 27 +/- 8 mg/dl) and fibrinogen (216 +/- 71 vs. 297 +/- 47)
      was lower in FK 506-treated patients. Our results indicate that FK 506
      immunosuppression offers some advantages in cardiovascular risk factors.

PMID- 9193848
TI  - Causes of renal allograft loss in black vs. white transplant recipients in the
      cyclosporine era.
AB  - Black renal transplant recipients have a higher rate of allograft loss than white
      recipients. From 1 January 1984 to 1 January 1995, 463 transplants were performed
      at a single center and followed for a mean duration of 71 months. The causes of
      graft loss for white and black recipients, their age, gender, retransplantation
      rate, organ source, and HLA matching were compared. In the 150 black and 313
      white recipients, graft loss rates in the first year were 20% in both groups,
      while after 1 yr there were 42 (28%) graft losses in blacks vs. 62 (20%) in
      whites (log-rank test p = 0.04). All diagnoses deemed causative of allograft loss
      were confirmed by biopsy. Chronic rejection resulting in graft loss occurred in
      15% (n = 23) of black recipients compared to only 7% (n = 22) of white recipients
      (p = 0.002). There were no significant differences in the rate of death with a
      functioning kidney or other causes of graft loss between the two groups. A
      significant increase in HLA mismatches was noted in black recipients of cadaveric
      grafts compared to whites, but there was no difference between races in the rate
      of graft loss due to acute rejection. While the rate of graft survival remains
      lower in black recipients in the cyclosporine era, this is due entirely to late
      graft loss after 1-yr post-transplant due to chronic rejection.

PMID- 9193850
TI  - Post-transplant lymphoproliferative disease in kidney transplant patients in the
      new immunosuppressive era.
AB  - Although the kidney transplant program at this center has been active for the
      past 18 yr, five out of the seven cases of post-transplant lymphoma in kidney
      transplant patients were observed over the past 2 yr. During this period, we have
      shifted from cyclosporine to tacrolimus (FK506 or prograf) for maintenance
      immunosuppression and for rescue therapy. We have also introduced mycophenolate
      (RS-61443) and have continued an antibody induction regimen in the immediate
      postoperative period. FK506 is 50-100 times more potent than cyclosporine. We
      have reported a decreased incidence of rejection, improved graft survival, and a
      general optimalization of patient survival with these newer regimens.
      Nonetheless, five cases of post-transplant lymphoma out of 233 kidney transplants
      (2.1%) performed during this time period (December 1993 to December 1995)
      occurred between 3 months to 1 yr after the transplant. Four of the five patients
      are still alive between 12 and 24 months after the diagnosis of lymphoma was
      made. All were without evidence of ongoing disease. Three of the five have grafts
      with excellent function for longer than 18 months after transplantation, while
      one is marginal and one patient expired on dialysis. The third and fourth
      patients had severe rejection before the diagnosis of PTLD was made. While the
      occurrence of five cases of post-transplant lymphoma over a 2 yr period is
      alarming, this is still within the 2-4% incidence of post-transplant lymphoma
      that has been reported in the literature in kidney transplant patients. Our
      results probably reflect the increasing potency of our immunosuppressive
      protocols but do not show any increase in the aggressiveness of this entity of
      post-transplant lymphoma during the continued follow up.

PMID- 9193849
TI  - Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in
      kidney transplant recipients.
AB  - This study was designed to (a) estimate the contribution of tacrolimus
      nephrotoxicity to episodes of renal allograft dysfunction investigated by needle
      biopsy, (b) describe the temporal evolution of nephrotoxicity and its response to
      therapy, and (c) ascertain how often renal dysfunction is associated with
      concurrent extra-renal toxicity. Patients were selected based on a rising serum
      creatinine, normal ultrasound, and biopsy findings leading to a reduction in the
      dose of tacrolimus and a fall in serum creatinine. Twenty two (17%) cases of
      nephrotoxicity were identified amongst 128 consecutive kidney transplant biopsies
      with sufficient clinical data for analysis. There were 13 males and 9 females, 17
      75 yr in age. Tacrolimus was administered initially as a 0.075-0.1 mg/kg/d IV
      continuous infusion followed by an oral dose of 0.15 mg/kg twice daily. The onset
      of nephrotoxicity in this study occurred 1-156 wk post-operatively. The mean
      baseline creatinine was 212.2 +/- 168.0 mumol/l (range 88.4-875.2) and rose 40.6%
      +/- 14.2% (range 11-66) during episodes of nephrotoxicity (p < 0.001). The
      highest recorded plasma and whole-blood tacrolimus levels during the toxic
      episodes were respectively 2.7 +/- 0.8 ng/ml (range 1.1-3.5) and 31.6 +/- 10.6
      ng/ml (range 14.5-50.5). The drug levels were considered to be beyond the
      therapeutic range in 18/22 (82%) patients. The highest tacrolimus level preceeded
      the rise in serum creatinine in 20 cases by an interval of 1.6 +/- 1.8 d. A mean
      reduction in tacrolimus dosage of 41% +/- 21% (range 11-89) led to a 86% +/- 18%
      (range 45-100) fall in the serum creatinine within 1-14 d (p < 0.001).
      Interactions between tacrolimus and clarithromycin, diltiazem, or itraconazole
      modified the pharmakokinetic parameters in three cases. Serum potassium > 5.0
      mequiv/l was recorded in 9/22 (41%) cases. Three or more elevations in blood
      glucose > 7.7 mmol/l (140 mg/dl) were recorded in 4/11 (36%) non-diabetic
      patients. Hand tremors were seen in two (9%) cases and elevated diastolic blood
      pressure > 90 mmHg in seven (32%) patients. In conclusion, tacrolimus
      nephrotoxicity accounted for 17% of graft dysfunction episodes investigated by
      biopsy. Concurrent hyperglycemia, hyperkalemia, or tremors were noted in several
      patients. Nephrotoxicity responded well to reduction in the drug dosage.

PMID- 9193851
TI  - Cytokines and pulmonary host defenses.
AB  - The generation of a vigorous inflammatory response is essential for rapid
      clearance of microbes from the alveolar space. The magnitude of the inflammatory
      response is tightly controlled by host-derived cytokines, which mediate lung
      inflammation by serving as leukocyte chemoattractants, leukocyte activating
      factors, or afferent signals in the induction or regulation of other effector
      molecules. In this chapter, the role of specific cytokines in lung innate and
      adaptive immunity against bacterial, mycobacterial, fungal, and parasitic
      pathogens is reviewed. Future directions regarding the use of specific forms of
      immunotherapy, including compartmentalized cytokine delivery using gene therapy,
      as adjuvant therapy in the treatment of pneumonia are explored.

PMID- 9193852
TI  - Incidence, etiologic pathogens, and diagnostic testing of community-acquired
      pneumonia.
AB  - Determination of the etiologic pathogens of community-acquired pneumonia has been
      problematic because of the lack of reliable rapid laboratory diagnostic tools as
      well as the controversy concerning diagnostic criteria. In the studies reviewed
      here, a specific pathogen was identified in 39% to 88% of patients. Streptococcus
      pneumoniae remains the most common cause of community-acquired pneumonia.
      Depending on the demographics of the study, between 2% to 43% of cases have been
      attributed to legionella or Chlamydia pneumoniae. More recently, other pathogens
      have emerged, including respiratory syncytial virus in adults, hantavirus, and
      possibly legionella-like amoebal pathogens and Streptococcus milleri group.
      Treatment guidelines published by various societies of experts have been helpful,
      but they cannot replace the need for better and rapid diagnostic techniques.

PMID- 9193853
TI  - Severe community-acquired pneumonia.
AB  - Severe community-acquired pneumonia is now considered a separate clinical entity
      that is important to recognize, particularly because of its high mortality rate.
      This article reviews several of the studies published in the past year that focus
      on risk and prognostic factors, etiology, diagnostic evaluation, pathogenesis,
      and therapy of this important condition.

PMID- 9193854
TI  - Bacterial infections of the bronchial tree.
AB  - In health, bacteria colonize the upper respiratory tract, but the lower
      respiratory tract defenses keep the lung sterile from the first bronchial
      division, despite being regularly challenged by bacteria from the nasopharynx and
      the environment. Bronchial infections reflect a failure that can be ascribed
      either to the virulence of the bacterium or to a deficiency of one or more of
      these defenses. An abnormality of the airway defenses, which may be inherited
      (e.g., cystic fibrosis) or acquired (e.g., following a viral infection or
      cigarette smoking), is present in most patients with bronchial infection, and
      this fact should be considered when planning investigation.

PMID- 9193855
TI  - Atypical pathogen pneumonia.
AB  - The term atypical pathogens has been applied in recent years to Chlamydia
      pneumoniae, Mycoplasma pneumoniae, and the various species of Legionella. The
      incidence of pneumonia caused by these pathogens has increased with the
      development of specific diagnostic techniques. Atypical pathogen community
      acquired pneumonia demonstrates a broad spectrum of severity from a mild disease
      not requiring hospitalization to adult respiratory distress syndrome
      necessitating mechanical ventilation. The clinical, radiological, and laboratory
      manifestations of the disease are similar to those of community-acquired
      pneumonia caused by other pathogens, and reliable etiological differentiation
      cannot be based on these factors alone. The possibility of shortening treatment
      time, at least in some patients, by antibiotic therapy with the new macrolides
      has been added to standard therapeutic regimens with erythromycin, tetracyclines,
      or quinolones.

PMID- 9193856
TI  - New perspectives in the diagnosis of nosocomial pneumonia.
AB  - In the past decade, much has been learned about the diagnosis of nosocomial
      pneumonia. Most of these reports focused on evaluating the diagnostic reliability
      of different techniques and identifying an adequate gold standard. In the past
      year, the most outstanding studies focused on practical issues such as developing
      more rapid and less invasive diagnostic techniques and tools, simplifying
      previously standardized techniques, and searching for safer and more cost
      effective procedures. Following the current trend, in the next few years we
      should spend more time learning about the impact of current techniques on outcome
      and less time looking for "El Dorado."

PMID- 9193857
TI  - Therapy for nosocomial pneumonia.
AB  - Because of a lack of clinical trials, the American Thoracic Society published a
      consensus statement on nosocomial pneumonia that included recommendations for
      antibiotic therapy. Almost concurrently, a multicenter study of the need to
      modify antibiotic therapy in ventilator-associated pneumonia (VAP) and a report
      specifically studying Pseudomonas VAP independently demonstrated both the
      appropriateness and some of the inadequacies of the therapies recommended by the
      American Thoracic Society. Anaerobic involvement as a copathogen was documented
      in early-onset VAP but probably impacts antibiotic choices little because of the
      presence of aerobic pathogens. Potential improvements in aminoglycoside treatment
      were suggested by meta-analysis of once-daily dosing and aerosolization. The most
      provocative study used decision-analysis techniques to suggest that antibiotic
      therapy based on clinical diagnosis of VAP would result in greater mortality than
      withholding antibiotics. Diagnosis of VAP by bronchoscopic and nonbronchoscopic
      quantitative cultures resulted in improved outcome with antibiotic treatment,
      possibly the result of documentation of inappropriate empiric antibodies in
      approximately 40% of cases of late-onset VAP.

PMID- 9193858
TI  - Respiratory illness in HIV-negative immunocompromised patients.
AB  - Pulmonary complications in immunosuppressed patients continue to be a source of
      morbidity and mortality. Prophylaxis, early recognition, and aggressive treatment
      remain the keys to management.

PMID- 9193859
TI  - Tuberculosis update: will good news become bad news?
AB  - Recent efforts to reestablish control of tuberculosis have resulted in some
      success. However, deaths from tuberculosis continue to increase worldwide.
      Molecular techniques have dominated investigators' efforts to improve diagnostic
      methods and therapeutic options. Unfortunately, no significant advances in the
      development of new drugs have occurred. Ongoing attempts to develop more
      effective vaccines hold some preliminary promise, but delineation of the
      protective antigens on Mycobacterium tuberculosis and the development of a
      vaccine for use in humans is considered decades away from clinical use. The lack
      of political commitment worldwide and the potential loss of support nationally
      remain major obstacles to the establishment of effective and long-lasting
      tuberculosis control.

PMID- 9193860
TI  - Nontuberculous mycobacteria.
AB  - The nontuberculous mycobacteria (NTM), especially Mycobacterium avium complex,
      are being recognized with increasing frequency as clinical pathogens, not only as
      a cause of disseminated disease in patients with AIDS but also as a cause of
      chronic lung disease in patients without AIDS. These infections have
      traditionally been difficult and frustrating to treat; however, the introduction
      of new agents, such as clarithromycin, azithromycin, and rifabutin, has
      significantly improved outcome for patients with some NTM infections. The new
      therapeutic regimens can be associated with severe toxicities and drug
      interactions that dictate the need for careful monitoring of patients undergoing
      treatment for M. avium complex disease. Clinicians will be called on with
      increasing frequency to determine the significance of NTM isolated from their
      patients. This determination will require knowledge about the pathogenicity and
      the appropriate therapy of a variety of NTM species.

PMID- 9193861
TI  - Fungal pneumonias.
AB  - An increased incidence of fungal pneumonias has been clearly seen in recent
      years, despite the lack of epidemiologic data. Pulmonary and extrapulmonary
      manifestations of blastomycosis, aspergillosis, and histoplasmosis, among others,
      are reviewed in this paper. The clinical presentation of pulmonary mycosis is
      influenced by the amount of exposure to the fungus and the host's immune
      response, and particular attention is paid in this review to the immunosuppressed
      patient. Recent reports of diagnostic tools such as bronchoscopy, imaging
      methods, and serologic tests are reviewed. Developments in aggressive therapies
      are discussed.

PMID- 9193862
TI  - Pulmonary complications of HIV infection.
AB  - With changes in epidemiology and the application of newer treatment and
      prophylactic regimens, the types of pulmonary diseases that occur in HIV-infected
      persons are changing. New ways to assess the progression of HIV disease and new
      antiretroviral treatments are available. Increased survival is often coupled with
      worsening immunosuppression. Overall mortality from Pneumocystis carinii
      pneumonia is declining, but mortality from bacterial pneumonia and mycobacterial
      disease is increasing. Infections with unusual and resistant organisms are also
      increasing. Patients with severe immunosuppression are susceptible to fungal,
      viral, and neoplastic pulmonary disease.

PMID- 9193863
TI  - Antimicrobial resistance: implications for managing respiratory failure.
AB  - The prevalence of antibiotic resistance in respiratory pathogens is increasing
      rapidly. In the community, resistance to beta-lactam antibiotics has escalated
      dramatically among Moraxella catarrhalis, Haemophilus influenzae, and
      Streptococcus pneumoniae. Resistance to penicillin among S. pneumoniae has
      developed at an alarming rate over the past two decades. Recent studies in the
      United States have cited rates of penicillin resistance as high as 23.6%, with
      9.5% exhibiting high-level resistance. Many of these strains are resistant to
      multiple antibiotics. Antimicrobial resistance in hospital-acquired pathogens is
      a problem, which in large part reflects patterns of antibiotic use. Antimicrobial
      resistance may arise via multiple mechanisms. Pseudomonas aeruginosa and other
      gram-negative bacilli have become increasingly resistant to beta-lactam
      antibiotics, including imipenem. Extended-spectrum beta-lactamases are seen with
      increasing frequency in Enterobacteriaceae, primarily Klebsiella spp.
      Fluoroquinolone resistance has increased in P. aeruginosa and Staphylococcus
      aureus and has now been identified in Escherichia coli isolated from hematology
      wards. Excessive use of antibiotics may promote the emergence and spread of
      resistant microorganisms. Rigorous infection control measures and modification of
      antibiotic use patterns may limit or reduce the prevalence of resistant
      organisms.

PMID- 9193865
TI  - Infectious diseases.

PMID- 9193864
TI  - Antibiotic penetration in the respiratory tract and implications for the
      selection of antimicrobial therapy.
AB  - There has been an increasing amount of information published recently about the
      ability of different antimicrobial agents to penetrate specific areas of the
      lung. Initially, whole lung concentrations were reported, but this methodology
      has been refined so that levels are now measured in potential sites of infection,
      such as the bronchial mucosa, epithelial lining fluid, and alveolar macrophages,
      as well as in sputum. Distinct differences in the ability to concentrate in these
      sites have been shown among beta-lactams, quinolones, and macrolides.
      Considerable intracellular concentration of quinolones and macrolides, but not
      beta-lactams, occurs. This intracellular accumulation has been used for the
      treatment of atypical mycobacteria. The potential effects of high antibiotic
      levels on cellular function have also been investigated. The clinical relevance
      of these findings for the choice of antimicrobial agent, dosage, formulation (eg,
      liposomal), and route of administration (eg, nebulized) are increasingly being
      explored.

PMID- 9193866
TI  - Metabolism of selegiline in humans. Identification, excretion, and
      stereochemistry of urine metabolites.
AB  - Nine urinary metabolites of selegiline hydrochloride [N-methyl-N-propargyl [2
      phenyl-1-methyl)ethylammonium chloride], a monoamine oxidase inhibitor, after
      administration to humans were identified. Their identifies were confirmed by
      comparison of the spectra from GC/MS of peaks with those of authentic compounds.
      The following metabolites and unchanged drug (selegiline) were detected in urine:
      (R)-desmethylselegiline, (R)-methamphetamine, (R)-amphetamine, (1S,2R)
      norephedrine, (1R,2R)-norpseudoephedrine, (1S,2R)-ephedrine, (1R,2R)
      pseudoephedrine, (R)-p-hydroxyamphetamine, and (R)-p-hydroxymethamphetamine. The
      metabolites excreted 2 days after administration of 2.5-10 mg of selegiline
      hydrochloride amounted to 44-58% of the dose. Selegiline was metabolized by three
      distinct pathways: N-dealkylation, beta-carbon hydroxylation, and ring
      hydroxylation. The major metabolite was (R)-methamphetamine. During metabolism,
      no racemic transformation occurred and beta-carbon hydroxylation showed
      apparently product stereoselectivity.

PMID- 9193867
TI  - Biotransformation of the novel inotropic agent toborinone (OPC-18790) in rats and
      dogs. Evidence for the formation of novel glutathione and two cysteine
      conjugates.
AB  - The metabolism of toborinone, (+/-)-6-[3-(3,4-dimethoxybenzylamino)-2
      hydroxypropoxy]-2(1H)-quin - olinone, a novel inotropic agent, was studied in
      rats and dogs after intravenous administration. Chemical structures of the 13
      metabolites were characterized by direct-probe FAB/MS and field desorption/MS,
      LC/FAB/MS, and various NMR measurements. After intravenous dosing of 10 mg/kg
      [14C]toborinone, fecal and urinary recoveries of the 14C dose were approximately
      70% and 26-30%, respectively, in both rats and dogs. The predominant component of
      radioactivity was the unchanged toborinone in every biological specimen in rats
      and dogs. Although unchanged toborinone was predominantly observed, toborinone
      underwent extensive conjugations with glucuronic acid, sulfate, and glutathione,
      either directly or following phase I reaction. Metabolites resulting from
      oxidative N-C cleavage were minor both in number and in quantity in every
      biological specimen in rats and dogs. In rats, toborinone underwent O
      demethylation to form M-7 and successive phase it reaction to yield the
      glucuronide M-1 and the sulfoconjugate M-2, and deconjugation to yield M-7, which
      was a primary metabolite accounted for 35.67% of the radioactivity excreted in
      the feces by 48 hr. Conjugates M-1 and M-2 were the major metabolites in rat
      plasma. In dogs, toborinone was metabolized via mercapturic acid pathway to yield
      the primary metabolites, cysteine conjugates M-10 and M-11 that accounted for
      19.10% and 6.70% of the radioactivity excreted in the feces by 48 hr and that
      were detected species specifically in dogs. The glutathione conjugate M-13, which
      was isolated from in vitro incubations using dog liver, led us to consider a
      possible mercapturic acid pathway from the parent compound to M-10. Metabolites
      in dog plasma and those in urine in both rats and dogs were minor in quantity.
      The metabolic pathways of toborinone in rats and dogs are proposed herein.

PMID- 9193868
TI  - Prediction of drug-induced catalepsy based on dopamine D1, D2, and muscarinic
      acetylcholine receptor occupancies.
AB  - It is known that catalepsy serves as an experimental animal model of
      parkinsonism. In this study, the relationship between in vivo dopamine D1 and D2
      receptor occupancies and catalepsy was investigated to predict the intensity of
      catalepsy induced by drugs that bind to D1 and D2 receptors nonselectively. 3H
      SCH23390 and 3H-raclopride were used for the labeling of D1 and D2 receptors,
      respectively. The ternary complex model consisting of agonist or antagonist,
      receptor, and transducer was developed, and the dynamic parameters were
      determined. After coadministration of SCH23390 and nemonapride, catalepsy was
      stronger than sum of the values predicted by single administration of each drug,
      and it was intensified synergistically. This finding suggested the existence of
      interaction between D1 and D2 receptors, and the necessity for constructing the
      model including this interaction. To examine the validity of this model,
      catalepsy and in vivo dopamine receptor occupancy were measured after
      administration of drugs that induce or have a possibility to induce parkinsonism
      (haloperidol, flunarizine, manidipine, oxatomide, hydroxyzine, meclizine, and
      homochlorcycilzine). All of the tested drugs blocked both dopamine D1 and D2
      receptors. Intensity of catalepsy was predicted with this dynamic model and was
      compared with the observed values. In contrast with haloperidol, flunarizine,
      manidipine, and oxatomide (which induced catalepsy), hydroxyzine, meclizine, and
      homochlorcyclizine failed to induce catalepsy. Intensities of catalepsy predicted
      with this dynamic model considering the interaction between D1 and D2 receptors
      overestimated the observed values, suggesting that these drugs have catalepsy
      reducing properties as well. Because muscarinic acetylcholine (mACh) receptor
      antagonists inhibit the induction of catalepsy, the anticholinergic activities of
      the drugs were investigated. After SCH23390, nemonapride and scopolamine were
      administered simultaneously; catalepsy and in vivo mACh receptor occupancy were
      measured to evaluate quantitatively the anticholinergic activity. Relationship
      between mACh receptor occupancy and change in catalepsy was used as the measure
      of catalepsy-reducing effects of the drugs. Measurement of in vivo mACh receptor
      occupancy revealed a significant blockade of mACh receptor by all of the tested
      drugs except for haloperidol. The predicted values of catalepsy, when corrected
      for the mACh receptor-related reduction, approached the observed values. This
      finding indicates the possibility that mACh receptor antagonism of drugs may
      contribute to the reduction of catalepsy. In conclusion, the dynamic model
      considering D1, D2, and mACh receptor occupancies and synergism between D1 and D2
      receptors may be useful for quantitative prediction of drug-induced catalepsy.

PMID- 9193869
TI  - Stereoselective metabolism of rac-mexiletine by the fungus Cunninghamella
      echinulata yields the major human metabolites hydroxymethylmexiletine and p
      hydroxymexiletine.
AB  - rac-Mexiletine is an orally effective class 1b antiarrhythmic agent used to treat
      ventricular arrhythmias. In vivo experiments have demonstrated. It is
      predominantly metabolized by the liver with < 10% excreted as unchanged drug. The
      major mammalian metabolites have been identified as p-hydroxymexiletine (PHM) and
      hydroxymethylmexiletine (HMM). The purpose of our study was to determine whether
      the fungus Cunninghamella echinulata, which possesses a cytochrome P450 system
      analogous to that found in humans, could be used as a suitable in vitro model for
      studying the oxidative metabolism of rac-mexiletine. To accomplish this, a high
      performance liquid chromatographic assay was used that was capable of
      simultaneously quantifying the enantiomers of mexiletine, HMM, and PHM. Utilizing
      this procedure, it was demonstrated that C. echinulata stereoselectively
      converted rac-mexiletine into HMM (4% of added drug) and PHM (32% of added drug)
      after an incubation period of 50 hr. In addition, metabolite biosynthesis could
      be optimized by altering fermentation media components. Seven media values and
      seven pH values were evaluated. It was determined that a medium at pH 7.0
      containing yeast extract and sucrose yielded optimal amounts of metabolites.

PMID- 9193870
TI  - Metabolism and disposition of the antifolate LY231514 in mice and dogs.
AB  - The metabolism and disposition of LY231514 was studied in mice and dogs. LY231514
      is a novel pyrrotopyrimidine-based multi-target antifolate (MTA) showing broad in
      vivo antitumor activity in mouse models and is currently in phase II human
      clinical trials. Doses (iv) of the compound showed high plasma levels, resulting
      in AUC values of 30-33 micrograms-hr/ml for mice and dogs after 20 and 7.5 mg/kg
      doses, respectively. The compound was eliminated rapidly. Half-life values for
      mice and dogs were about 7 and 2 hr, respectively. In vitro plasma binding
      measured 56% in mice, 46% in dogs, and 81% in humans. Fecal elimination was the
      major excretion pathway in mice after single iv doses of [14C]LY231514. Urine
      constituted the major route of excretion in dogs. Parent LY231514 accounted for
      the majority of urinary radiocarbon in mice (90%) and dogs (68%). Minor
      metabolites were found in urine, but the amounts were too small to isolate or
      identify. Based on an earlier observation that LY231514 photodegraded to produce
      reaction products having similar retention times as these minor urinary isolates,
      a photo-oxidation system was developed which in fact produced these metabolites.
      Subsequently, these photolytically-produced materials were used as standards to
      identify two novel in vivo metabolites formed by oxidation of the pyrrolo
      pyrimidine ring system of LY231514. The oxidative transformations are similar to
      those observed for tryptophan and other indoles in that the pyrrole ring is
      oxidized to give an amide; further oxidation cleaves this ring, one ring carbon
      is lost, and a ketone is formed.

PMID- 9193871
TI  - Disposition and metabolism of the sulfonylurea oncolytic agent LY295501 in mouse,
      rat, and monkey.
AB  - The disposition and metabolism of LY295501 was studied in mice, rats, and
      monkeys. This novel diaryl sulfonylurea oncolytic agent is structurally related
      to sulofenur and shows excellent activity in a broad range of mouse antitumor
      models. The compound is well absorbed, giving plasma concentrations greater than
      200 micrograms/ml after oral doses of 30-100 mg/kg, where it appears to be
      completely bound (> 99.9%) to plasma proteins. The high degree of protein binding
      may be a factor in its relatively long half-life, which ranges from about 8 hr in
      rats and 15 hr in mice to 50 hr in monkeys. While more material was excreted in
      feces than in urine from mice and rats given single oral doses of [14C]LY295501,
      urine was the major route of elimination in monkeys. Three major metabolites-all
      formed via oxidation of the saturated part of the benzodihydrofuran moiety-were
      characterized in the urine of mice, rats, and monkeys. It is interesting that two
      of these metabolites are derived from opening of this saturated ring, an unusual
      metabolic process which represents a significant part of the metabolism of
      LY295501. As with sulofenur, metabolites of 3,4-dichloroaniline formed after
      metabolic cleavage of the sulfonylurea linkage were also found in urine. Unlike
      sulofenur, these do not seem to have major toxicological significance, but their
      formation does explain the minor methemoglobinemia observed in toxicology studies
      of LY295501. Even though only trace amounts of LY295501 were found in urine,
      LY295501 is the predominant drug-related material in plasma, along with small
      amounts of other, relatively nonpolar, metabolites.

PMID- 9193872
TI  - Microbial models of mammalian metabolism. Biotransformations of HP 749
      (besipirdine) using Cunninghamella elegans.
AB  - HP 749 (besipirdine; Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) and
      related analogs belonging to the N-(4-pyridinyl)-1H-indol-1-amine class of
      compounds have shown a potential to mitigate multiple biochemical deficits
      associated with Alzheimer's disease. HP 749 has demonstrated cholinergic and
      nonadrenergic activities both in vitro and in vivo, and has potential for the
      symptomatic treatment of Alzheimer's disease. The three primary metabolites of HP
      749 in dogs, rats, and humans result from hydroxylation of the indole ring, N
      dealkylation of the parent compound, and sequential hydroxylation and
      dealkylation. The fungus Cunninghamella elegans (ATCC 36112) converts 25% of HP
      749 in a dextrose broth to yield four metabolites, three of which have been
      reported in mammalian systems. Preparative scale fermentation allowed for the
      isolation of the major fungal metabolite resulting from hydroxylation of the
      indole nucleus at position 5 (16%), which was characterized by cochromatographic
      (TLC and HPLC), 1H-NMR, mass spectral (chemical ionization/MS), and UV
      comparisons to a synthetic standard. Additional minor fungal metabolites were
      formed as a result of N-dealkylation (2%), and sequential N-dealkylation and
      aromatic hydroxylation (2.5%). C. elegans is being used as a model to help
      predict and generate the logical mammalian metabolites of related structural
      analogs of HP 749.

PMID- 9193873
TI  - Cytochrome P450 responsible for the stereoselective S-oxidation of flosequinan in
      hepatic microsomes from rats and humans.
AB  - The forms of cytochrome P450 involved in the stereoselective S-oxidation of
      flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulfinyl-4-quinolone] were
      investigated in vitro using liver microsomes from rats and humans. Rat liver
      microsomes supplemented with NADPH catalyzed the four different S-oxidations,
      which were from flosequinan sulfide (FS; 7-fluoro-1-methyl-3-methylthio-4
      quinolone) to R(+)- and S(-)-flosequinan (R-FSO and S-FSO, respectively) and from
      R-FSO and S-FSO to flosequinan sulfone (FSO2; 7-fluoro-1-methyl-3-methylsulfonyl
      4-quinolone). The activities of all the S-oxidases in liver microsomes from male
      rats were higher than those from female rats. The activities of the S-oxidases
      measured at a high substrate concentration (1 mM) were induced by treatment of
      rats with phenobarbital and dexamethasone. Treatment of rats with 3
      methylcholanthrene also induced the activities, but only at a low substrate
      concentration (50 microM), except for the S-oxidase catalyzing the reaction from
      FS to R-FSO. Enzymes induced by clofibrate and ethanol were not involved in the
      oxidations at a low substrate concentration. The activities of S-oxidases were
      correlated with the contents of cytochrome P450 (CYP)3A enzymes. Anti-CYP3A2
      antisera inhibited the activities of the S-oxidases catalyzing the reactions from
      FS to R-FSO (40%) and to S-FSO (60%) at the high substrate concentration and
      inhibited the activities of the S-oxidases, thus catalyzing reactions from R-FSO
      and S-FSO to FSO2 (70%) at both high and low substrate concentrations. These
      results suggest that CYP3A is the major enzyme involved in all S-oxidation
      pathways in flosequinan metabolism in rats. On the other hand, except for the S
      oxidation of FS to R-FSO, the rates of the other three S-oxidations by liver
      microsomes from 30 individual humans correlated highly with each other,
      suggesting that the same enzyme would be involved in the three S-oxidations. Anti
      CYP3A2 antisera inhibited the activities of all the S-oxidases in human liver
      microsomes ranging from 40 to 80%, suggesting that CYP3A is also involved in all
      of the S-oxidations of flosequinan in humans.

PMID- 9193874
TI  - Purification and 1H NMR spectroscopic characterization of phase II metabolites of
      tolfenamic acid.
AB  - Tolfenamic acid, an anti-inflammatory drug (NSAID), is metabolized in vivo to
      form several oxidative metabolites which are all conjugated with beta-D
      glucuronic acid. In this study, the metabolites of tolfenamic acid were
      identified by 1H nuclear magnetic resonance (NMR) spectroscopy in urine samples
      obtained on days 7 to 10 from a human volunteer after oral administration of 200
      mg of the drug three times per day (steady-state plasma concentration). The
      metabolites of tolfenamic acid were initially concentrated by preparative solid
      phase extraction (PSPE) chromatography, thereby removing the endogenous polar
      compounds that are present in the urine. The individual metabolites were purified
      by preparative high performance liquid chromatography (HPLC) and then identified
      using 1H NMR. Both one- and two-dimensional NMR experiments were performed to
      identify the phase II metabolites of tolfenamic acid; the study shows the
      applicability of 1H NMR for the identification of drug metabolites in biological
      fluids. In addition to NMR analysis, two metabolites were also identified by mass
      spectrometry (MS). The glucuronides of the following parent compounds, N-(2
      methyl-3-chlorophenyl)-anthranilic acid (T), N-(2-hydroxymethyl-3-chlorophenyl)
      anthranilic acid (1), N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic
      acid (2), N-(2-formyl-3-chlorophenyl) anthranilic acid (3), N-(2-methyl-3-chloro
      4-hydroxyphenyl)-anthranilic acid (4), N-(2-methyl-3-chloro-5-hydroxyphenyl)
      anthranilic acid (5), N-(2-carboxy-3-chlorophenyl)-anthranilic acid (6), N-(2
      hydroxymethyl-3-chlorophenyl)-4-hydroxy-anthranilic acid (7), N-(2-methyl-3
      chlorophenyl)-5-hydroxy-anthranilic acid (8), N-(2-methyl-3-chloro-4
      metoxyphenyl)-anthranilic acid (9), N-(2-methyl-3-chlorophenyl)-4-hydroxy
      anthranilic acid (10), and N-(2-methyl-4-hydroxyphenyl)-anthranilic acid (11)
      were identified. The phase II metabolites (5-11) had not previously been
      identified in urine from humans administered tolfenamic acid. The phase I
      metabolites of the glucuronides 7, 8, 10, and 11 were identified here for the
      first time. An HPLC method was developed that simultaneously separates all the
      phase II metabolites identified as well as some phase I metabolites in urine
      samples obtained after intake of tolfenamic acid.

PMID- 9193875
TI  - Oral and topical absorption, disposition kinetics, and the metabolic fate of
      trans-methyl styryl ketone in the male Fischer 344 rat.
AB  - trans-Methyl styryl ketone (MSK; trans-4-phenyl-3-buten-2-one) is a beta
      unsaturated ketone that has a wide range of uses in industry and is present in
      numerous consumer products. Although MSK has been shown to be positive in several
      in vitro mutagenic assays, it does not seem to be overtly toxic in animal models.
      This lack of toxicity may relate to its poor absorption and/or rapid elimination.
      However, little is known about the fate of MSK in the body. Studies were
      conducted to characterize the absorption, and disposition kinetics of MSK after
      intravenous, oral, and topical administration to male Fischer 344 rats. After
      intravenous administration of [14C]MSK (20 mg/kg, 120 microCi/kg), blood
      concentration-time data could be characterized with a biexponential equation and
      apparent first-order elimination kinetics. The following pharmacokinetic
      parameter values were obtained (mean +/- SD): terminal disposition half-life,
      17.7 +/- 0.08 min; apparent steady-state volume of distribution, 0.89 +/- 0.14
      liters/kg; systemic body clearance, 68.9 +/- 10.0 ml/kg *min; and mean residence
      time, 13.1 +/- 2.2 min. Within 48 hr, 95.5% of the dose was excreted in the urine
      and 2.7% in the feces. The major blood metabolite after intravenous
      administration was identified by GC/MS as the 4-phenyl-3-buten-2-ol (methyl
      styryl carbinol). After oral administration of [14C]MSK (200 mg/kg, 100
      microCI/kg), approximately 96.6% of the dosed radioactivity was recovered in the
      urine and 4.8% in the faces within 48 hr. Major urinary metabolites identified by
      LC-MS/MS and quantified by HPLC radioassay were N-phenylacetyl-L-glycine (64.9%
      of dose) and N-benzyl-L-glycine (9.9% of dose). Parent compound could not be
      detected in the blood after oral administration, and 14C-equivalents in the blood
      never exceeded 1.3% of the dose. Results suggest near-total presystemic
      elimination of the oral dose. After topical application of [14C]MSK (250 mg/kg,
      50 microCi/kg), > 60% of the dose was absorbed, and the majority of the dose was
      excreted into the urine (55% of dose) in the form of metabolites. Urinary
      metabolites were similar to those described after oral administration. 14C
      equivalents were not detected in the blood at any time after topical
      administration. These results indicate that MSK is almost totally metabolized
      before systemic distribution after oral or topical administration. The systemic
      exposure dose of MSK seems to be exceedingly low at the doses studied herein.

PMID- 9193876
TI  - Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by
      cDNA-expressed human cytochrome P-450 isozymes.
AB  - The metabolism of nortriptyline was studied in vitro using cDNA-expressed human
      cytochrome P450 isozymes 1A2, 3A4, 2C19, and 2D6, CYP2D6 was the sole isozyme
      mediating hydroxylation of nortriptyline, the quantitatively most important
      metabolic pathway, and only (E)-10-OH-nortriptyline was formed. CYP2D6, 2C19, and
      1A2, mentioned in decreasing order of significance, mediated the demethylation
      reaction of nortriptyline, whereas 3A4 did not participate in the metabolism of
      nortriptyline. Concerning the quantitative relations, CYP2D6 exhibited a high
      affinity with respect to hydroxylation and demethylation (K(m) 0.48-0.74
      mumol/l), a high hydroxylation capacity (Vmax 130 mol/hr/mol CYP) and a somewhat
      lower demethylation capacity (Vmax 19 mol/ hr/mol CYP). The affinities of 1A2 and
      2C19 were 100-fold lower (K(m) 54-118 mumol/l). The capacity of 1A2 was low (Vmax
      6.8 mol/hr/ mol CYP), whereas 2C19 had the highest demethylation capacity (Vmax
      93 mol/hr/mol CYP). Taking into account the relative amounts of CYP isozymes
      present in the liver, about 90% of the metabolism was estimated to depend on
      CYP2D6, with CYP2C19 and 1A2 mediating the remaining 10%. In subjects lacking the
      2D6 isozyme, CYP2C19 and 1A2 are expected to be of major importance for
      elimination of nortriptyline.

PMID- 9193877
TI  - Baculovirus-directed expression of rabbit UDP-glucuronosyltransferases in
      Spodoptera frugiperda cells.
AB  - The rabbit liver UDP-glucuronosyltransferase (UGT) cDNAs that encode the 4
      hydroxybiphenyl UGT2B13 and 4-nitrophenol UGT1A6 have been cloned into
      baculovirus. Spodoptera frugiperda (SF-9) cells infected with the UGT recombinant
      baculovirus produced significant amounts of protein, which was detected by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, and
      pulse chase with 35S-amino acids. The expression of the UGT proteins in SF-9
      cells were detected at approximately 24 hr postinfection, with maximal levels of
      protein seen at 48 hr. Immunoprecipitation of newly synthesized 35S-labeled
      proteins demonstrated that the maximal rate of protein synthesis in SF-9 cells
      infected with the UGT baculovirus occur at 48 hr postinfection, although the
      proteins are abundant in the cells for up to 96 hr. When compared with the
      expression levels of the same cDNAs through transient transfection into COS-1
      cells, the insect-derived UGT proteins showed nearly 50- to 100-fold greater
      protein accumulation. Although kinetic analysis demonstrated that turnover rate
      of the SF-9-expressed proteins were greater than their counterparts in COS-1
      cells, K(M) values for UGT1A6 and UGT2B13 in SF-9 and COS-1 cells were similar.
      Overall, SF-9 cells seem to serve as an efficient expression system for the
      production of the mammalian UGTs.

PMID- 9193878
TI  - In vivo induction and in vitro inhibition of hepatic cytochrome P450 activity by
      the benzodiazepine anticonvulsants clonazepam and diazepam.
AB  - The ability of the benzodiazepines, as a chemical class, to cause the induction
      and/or inhibition of cytochromes P450 has not been well characterized. In the
      present study, the induction of the cytochrome P450 2B subfamily (CYP2B) in vivo
      and the inhibition of CYP2B activity in vitro by selected benzodiazepines was
      examined in hepatic tissues derived from male F344/NCr rats. Initial studies of
      the in vivo induction or in vitro inhibition of benzyloxyresorufin O-dealkylation
      activity revealed that both clonazepam and diazepam were relatively effective in
      vivo inducers of CYP2B when administered in the diet at 500 ppm for 5 days and
      also were fairly potent inhibitors of the activity of these hemoproteins in
      vitro. Oxazepam, in contrast, was ineffective as an inducer or an inhibitor of
      this activity. Further studies were performed to characterize the subfamily
      selectivity of the P450 induction and inhibition displayed by clonazepam.
      Specifically, microsomes from rats treated with clonazepam (1000 or 1800 ppm in
      the diet for 5 days) were found to be highly induced with respect to catalytic
      activities mediated by CYP2B, including benzyloxyresorufin and pentoxyresorufin O
      dealkylation or testosterone 16 beta-hydroxylation, but other CYP proteins were
      minimally induced. In addition to inducing the CYP2B subfamily, clonazepam also
      induced the RNA encoding other drug metabolizing enzymes (e.g., epoxide hydrolase
      and the glutathione S-transferase alpha-subfamily) that are typically induced by
      phenobarbital-type inducers. Finally, clonazepam proved to be a potent
      noncompetitive or "mixed-type" competitive inhibitor of catalytic activities
      mediated by CYP2B, but not by other CYP proteins (e.g. CYP2A, CYP3A) in
      microsomes derived from phenobarbital-pretreated rats.

PMID- 9193879
TI  - Induction of cytochrome P4503A by the antiglucocorticoid mifepristone and a novel
      hypocholesterolaemic drug.
AB  - Rat liver microsomal testosterone (250 microM) hydroxylation and immunoreactive
      CYP3A protein were compared after administration of the antiglucocorticoid RU 486
      (50 mg.kg-1.day-1 for 4 days) and the hypocholesterolaemic drug SR-12813 (150
      mg.kg-1.day-1 for 4 days). Markers of CYP3A-mediated enzyme activity
      (testosterone 15 beta-, 6 beta-, and 2 beta-hydroxylation) were increased after
      administration of both drugs. Testosterone 6 beta-hydroxylation was increased 5
      fold by RU 486 and 9-fold by SR-12813. Administration of dexamethasone alone at
      150 mg.kg-1.day-1 or in combination with RU 486 induced testosterone 6 beta
      hydroxylation 15- to 20-fold. The lack of antagonistic effect of RU 486 on
      dexamethasone-mediated CYP3A induction strengthens support for the hypothesis
      that the "classical glucocorticoid receptor" does not play a part in this
      process. The induction of CYP3A enzymes by the bisphosphonate SR-12813 suggests
      the existence of a new class of compounds with CYP3A inducing properties.

PMID- 9193880
TI  - Inhibitory anti-peptide antibody against human CYP3A4.
AB  - An inhibitory anti-peptide antibody was raised against a 21-amino acid peptide
      (VKRMKESRLEDTQKHRVDFLQ) corresponding to residues 253-273 of human cytochrome
      P450 3A4. High titer antibodies were produced by rabbits immunized with this
      peptide coupled to keyhole limpet hemocyanin, as judged by ELISA. Anti-peptide
      antibody recognized a single protein band in microsomes prepared from cells
      expressing recombinant human CYP3A4 in immunoblotting analysis. No
      immunodetectable proteins were found in microsomes containing other cytochrome
      P450 isoforms. In addition, the antibody did not recognize CYP3A5, a closely
      related isoform in the CYP3A family. In human liver microsomes, only one protein
      band which comigrated with human CYP3A4 was recognized by this antibody and the
      relative blotting intensity of this protein band correlated significantly with
      human CYP3A4-catalyzed testosterone 6 beta-hydroxylase activities (r = 0.96).
      More importantly, this antibody exhibited greater than 90-95% inhibition of
      testosterone 6 beta-hydroxylation, while other cytochrome P450-mediated reactions
      in human liver microsomes were not inhibited. Because of its specificity and
      inhibitory potency, this anti-peptide antibody should be a valuable tool in
      evaluating the role of CYP3A in mediating in vitro metabolism of therapeutic
      agents.

PMID- 9193881
TI  - Blood-brain barrier permeability to morphine-6-glucuronide is markedly reduced
      compared with morphine.
AB  - The blood-brain barrier (BBB) permeability to morphine and morphine-6-glucuronide
      (M6G) is measured under identical conditions using an intravenous injection
      method in the rat and HPLC separation of morphine from its metabolites. The brain
      uptake of M6G expressed as %ID/g was 32-fold lower than that of morphine, and the
      BBB permeability surface area product (PS) of M6G was 57-fold lower as compared
      with that of morphine. Consistent with these in vivo data, the 1-octanol/buffer
      partition study showed the liposolubility of M6G was 187-fold lower than that of
      morphine. The CNS origin of M6G analgesia after peripheral administration was
      confirmed because the analgesia was completely blocked by naloxone, which crosses
      BBB, but not by naloxone methiodide, which does not enter brain from blood. In
      conclusion, the BBB permeability to M6G is markedly reduced as compared with
      morphine, consistent with the much lower lipid solubility of M6G relative to
      morphine.

PMID- 9193882
TI  - Metabolism of ketoconazole and deacetylated ketoconazole by rat hepatic
      microsomes and flavin-containing monooxygenases.
AB  - Ketoconazole (KT) has been reported to cause hepatotoxicity, which is probably
      not mediated through an immunoallergic mechanism. Although KT is extensively
      metabolized by hepatic microsomal enzymes, the nature, route of formation, and
      toxicity of suspected metabolites are largely unknown. Recent reports indicate
      that N-deacetyl ketoconazole (DAK) is a major initial metabolite in mice, which,
      like lipophilic 4-alkylpiperazines, is susceptible to successive oxidative
      attacks on the N-1 position producing ring-opened dialdehydes. The rate of
      formation of DAK from hepatic rat microsomal incubations of KT was determined by
      HPLC. The rate of disappearance for KT was almost equal to the rate of DAK
      formation: 5.96 and 5.88 microM/hr, respectively. Also, the potential
      bioactivation of DAK was evaluated by measuring substrate activity of DAK with
      purified pig liver flavin-containing monooxygenase (FMO) and rat liver
      microsomes. Activity was measured by following DAK-dependent oxygen uptake
      polarographically at 37 degrees C in pyrophosphate buffer (pH 8.8) containing the
      glucose-6-phosphate NADPH-generating system. The K(M)'s of DAK were 34.6 and 77.4
      microM for the purified FMO and rat microsomal FMO, respectively. Lastly, DAK was
      found to be metabolized by an NADPH-dependent rat liver microsomal monooxygenases
      at pH 8.8 to two metabolites as determined by HPLC. Heat inactivation of rat
      liver microsomal FMO abolished the formation of these metabolites from DAK. SKF
      525A and anti-rat NADPH cytochrome P450 reductase did not inhibit this reaction.
      These results suggest that deacetylation of KT yields a major product, DAK, for
      further metabolism by microsomal monooxygenases that seem to be FMO-related.

PMID- 9193883
TI  - The menopause transition.
AB  - New paradigms for the study of menopause will increase our understanding of
      whether symptoms, syndromes, and chronic diseases are associated with menopause.
      Rather than considering menopause as a discrete event, it has become clear that
      the menopause transition takes place over many years. Although this realization
      is central to our understanding of menopause, it is difficult to measure the
      temporal pattern of changes in hormones and their relation to concurrent or
      subsequent health-related events. The model of hormonal changes at the time of
      the transition has been expanded to include not only declines in estrogen but
      changes in a broader range of hormones, including the potential role of
      androgens. New models are attempting to account for the pattern and frequency of
      changes in hormone levels. Another level of complexity is contributed by the
      expansion of the menopause model to include comorbid medical and psychiatric
      conditions, environmental influences, and behaviors as covariates that influence
      the expression of menopause-related events. Although this more complicated
      paradigm makes the conduct of menopause research more challenging, it is also
      likely to elucidate previously confusing data, as the proper understanding of
      potentially complex exposures, effect modifiers, and confounders is more likely
      to provide clearer answers to critical research questions.

PMID- 9193884
TI  - Mood disorders and menopause.
AB  - Studies of depressive symptoms in menopausal women indicate that menopause is not
      associated with increased rates of depression, although mild mood and anxiety
      symptoms may occur in the few years prior to menopause. Women with previous
      affective disorders that are cyclic or that are associated with reproductive
      events may be at increased risk for depression at menopause. Because women
      presenting to menopause clinics are more likely to have affective disorders, the
      efficacy of estrogen for enhancing mood is an important question. Although some
      researchers suggest that estrogens have proven mood-elevating and antidepressant
      properties, others caution that the psychologic benefits of HRT deserve more
      systematic study before conclusions can be made. It has been suggested that minor
      psychologic symptoms at menopause or psychologic symptoms accompanied by
      vasomotor symptoms warrant a trial of HRT before considering psychotropic
      medication. If the psychologic symptoms do not respond to HRT, are not
      accompanied by vasomotor symptoms, or are clinically severe, antidepressant
      medication should be considered first or in addition to HRT. The psychologic
      effects of progesterone and androgens are less extensively studied than those of
      estrogen, and further research is needed.

PMID- 9193885
TI  - The pathophysiology and treatment of postmenopausal osteoporosis. An evidence
      based approach to estrogen replacement therapy.
AB  - Osteoporosis is one of the most common and debilitating diseases of
      postmenopausal women. Recent advances in understanding the bone remodeling unit
      have clarified the pathophysiologic processes that contribute to bone loss after
      the onset of estrogen deprivation. Epidemiologic studies have suggested a
      protective effect from long-term estrogen replacement therapy on fracture risk.
      This article examines the key role estrogens play in bone remodeling and the
      current evidence that estrogen treatment in postmenopausal women reduces the
      likelihood of osteoporotic fractures.

PMID- 9193886
TI  - The effects of hormone replacement therapy on coronary heart disease.
AB  - The importance of cardiovascular disease as a cause of morbidity and mortality in
      women is well appreciated. Cardiovascular disease accounts for approximately 48%
      of deaths in women in the United States. In particular, coronary heart disease
      (CHD) accounts for approximately one-half of these deaths. This article describes
      current evidence that suggests it is premature to recommend hormone replacement
      therapy (HRT) as a proven prevention strategy for CHD.

PMID- 9193887
TI  - Hormone replacement therapy and other potential treatments for dementias.
AB  - The past decade has seen a substantial increase in the number of individuals
      affected by dementia. Dementia places a tremendous personal and economic burden
      on millions of patients and caregivers annually. Consequently, many scientists
      have been searching for a treatment for dementia to avoid the imminent public
      health crisis that will occur if this trend continues. Primary and secondary
      prevention studies, as well as animal research, demonstrate the potential for
      hormone replacement therapy (HRT) as an efficacious treatment for dementia.
      Recently, the Women's Health Initiative-Memory Study began the first randomized,
      longterm clinical trial to test the hypothesized role of HRT at the onset and in
      the progression of dementia in women. Researchers also are investigating the
      potential of other treatments for dementias, such as nonsteroidal anti
      inflammatory drugs and free radical scavengers.

PMID- 9193888
TI  - The role of estrogen replacement therapy in the management of urinary
      incontinence and urinary tract infection in postmenopausal women.
AB  - The hormonal changes associated with normal aging and menopause may contribute to
      the development of urinary disorders including both urinary incontinence and
      urinary tract infections. Estrogen replacement therapy has been used successfully
      in the treatment of both of these disorders in postmenopausal women. Although the
      selection of specific treatment modalities should be tailored to the individual
      patient, hormonal replacement should be considered a viable conservative
      treatment option for many older women with urinary complaints. Future research
      will help to delineate the most effective route of administration and type of
      estrogen used in treating these complaints.

PMID- 9193889
TI  - Hormone replacement therapy and risk for breast cancer.
AB  - Because breast cancer will develop in one of every nine American women, even a
      small increase in risk associated with a widespread exposure is of substantial
      public health concern. Although most studies have not found ever use of estrogens
      to be a risk factor for breast cancer, it is not yet resolved whether current or
      long-term users experience some increase in risk. Given the fact that the
      indications for menopausal estrogen use have changed substantially over time,
      from short-term use for the relief of menopausal symptoms to long-term use for
      lifetime reduction of conditions such as cardiovascular disease and osteoporosis,
      it is imperative that the effects of long-term estrogen replacement on the risk
      for breast cancer be resolved. These studies are not without associated
      methodologic difficulties, with the ultimate interpretation of the association
      possibly dependent on the results of controlled clinical trials. Although such
      investigations are currently underway, the results will not be available for many
      years. To address more immediate concerns, continued emphasis should be placed on
      well-designed case-control and cohort studies. For the results to be reliable,
      attention must be directed to the effects of selection, recall and surveillance
      biases, confounding factors, detailed exposure relationships, subgroup
      variations, and disease associations. In addition, given the increasing trend for
      estrogens to be prescribed in combination with progestogens, the effects on
      breast tissue of this combined therapy merit immediate attention.

PMID- 9193891
TI  - The role of androgens in menopausal hormonal replacement.
AB  - Androgen therapy may improve libido and psychologic symptoms in hypogonadal
      women. Such replacement may also cause undesirable lipoprotein changes and
      virilizing side effects. By detailing the benefits and risks, this article may
      help the clinician determine the role of androgen therapy as a supplement to
      conventional estrogen/progestin replacement in menopausal women.

PMID- 9193890
TI  - Nonestrogen management of menopausal symptoms.
AB  - Women who cannot or choose not to take estrogens do have alternatives; however,
      the options are few and unproven in longterm clinical trials with respect to
      safety and efficacy. Many available alternative treatments may alleviate the
      symptoms of the menopause, but do not convey long-term protection against
      osteoporosis and cardiovascular disease. This article reviews treatment
      alternatives to estrogen replacement therapy for symptomatic relief.

PMID- 9193892
TI  - Endometrial cancer and hormone replacement therapy. Appropriate use of progestins
      to oppose endogenous and exogenous estrogen.
AB  - Most instances of endometrial cancer are potentially preventable. Unopposed
      endogenous estrogen stimulation of the endometrium has been shown to be the
      predisposing risk factor in most cases. Risk factors have been well-delineated,
      and it is important to recognize and treat the progesterone-deficient patient.
      Low-dose oral contraceptive pills in healthy, nonsmoking, older reproductive-aged
      women are an underutilized treatment modality. The many noncontraceptive benefits
      of longterm oral contraceptive use until the menopause should be explained to the
      patient, including the prevention of ovarian and endometrial cancer, the
      maintenance of bone density, and a reduction in the many surgical procedures
      performed for menstrual disorders. Progestin therapy in older reproductive-aged
      women and postmenopausal women with unopposed estrogen production is mandatory to
      prevent endometrial cancer. Knowledge and skill in simple endometrial sampling
      techniques performed in patients with known risk factors for endometrial cancer
      will often detect premalignant lesions that are treatable with progestin therapy
      or surgery.

PMID- 9193893
TI  - The clinical decision regarding hormone replacement therapy.
AB  - The complexity of the decision to recommend hormone replacement therapy (HRT) for
      the postmenopausal woman depends on the medical status of the patient, her
      concerns and goals, and the indications being considered. This article suggests a
      practical approach that leads to informed, collaborative decision making between
      the health care professional and patient.

PMID- 9193894
TI  - Life history evolution in guppies (Poecilia reticulata): guppies as a model for
      studying the evolutionary biology of aging.
AB  - Natural populations of guppies can be found with different communities of
      predators. We have contrasted the early life history of guppies from high and low
      predation localities. Life history theory predicts that such differences in
      mortality pattern will select for evolutionary changes in the guppy's life
      history. Specifically, guppies in high-predation localities are predicted to
      mature at an earlier age and devote more of their resources to reproduction. We
      have demonstrated the predicted differences in life history patterns with
      experiments and observations on guppies from each type of locality. We have also
      selected for the predicted changes in the life history by manipulating mortality
      patterns in natural populations. Theories for the evolution of senescence predict
      that these same mortality patterns will also select for changes in the rate of
      aging. Specifically, guppies from high-predation localities should have higher
      rates of aging than their counterparts from low-predation localities. Experiments
      that select for changes in the early life history should also select for changes
      in the rate of aging. The existing work on guppies, therefore, presents the
      opportunity to use them as a new experimental system for studying the
      evolutionary biology of aging. Finally, I present preliminary results from a
      pilot study of aging in guppies. This study differs from the earlier work by
      Comfort because these fish have been reproductively active since they attained
      maturity; Comfort's fish were maintained as virgins throughout their lives. This
      study makes two important points. First, age-specific changes in reproductive
      performance represent as important an index of aging as mortality rates. Second,
      the rate of aging may be far more rapid in reproductively active individuals.

PMID- 9193895
TI  - Multiphasic models of survival: analysis of mortality rate change regions and the
      issue of finite species lifespan.
AB  - Recent large-scale experimental population studies have allowed us to probe the
      dynamics of survival in the "oldest old" of a small number of biological species.
      The results of these studies add strong support to the validity of a multiphasic
      survival/mortality model for population survival as has been previously proposed
      by a number of investigators. In this paper we briefly review some of the
      problems with the Gompertz survival model, and the issue of locating the region
      in which the mortality rate might change. We derive some rigorous formulae for
      bounding the mortality rate change regions and compare the predictions to the
      available experimental data. We demonstrate that the mortality cut point
      parameter appears to be directly related to topological properties of the species
      survival curve, in particular, the inflection time. We conclude by addressing
      some of the pitfalls of using a mortality cut point model and propose an
      alternative formulation for a mortality model involving multiphasic mortality
      dynamics and incorporating a nonspecified upperbound on species lifespan.

PMID- 9193896
TI  - Intersections of mortality-rate and survival functions: model-independent
      considerations.
AB  - In work reported previously (Hirsch, 1995), it was shown that families of
      straight lines intersect at a single point if and only if the slopes of the lines
      are linearly related to their intercepts. This slope-intercept relation was
      applied to several mathematical mortality models including the Gompertz-Makeham
      and the Weibull. In all cases, survival functions intersected at greater ages
      than the corresponding mortality-rate functions. It was further demonstrated that
      a common point of intersection can exist for members of a family of survival
      functions or for members of the corresponding family of mortality-rate functions
      but not for both. Here the same results are obtained with respect to
      intersections of general model-independent survival and mortality-rate functions.
      The generality of the results strengthens the conclusion reached earlier that
      these intersections imply only the existence of a valid slope-intercept relation
      and have little other significance with regard to the biology of aging.

PMID- 9193897
TI  - Relationship between pituitary hormones, antioxidant enzymes, and
      histopathological changes in the mammary gland of senescent rats.
AB  - In order to assess the possible involvement of endocrine factors and antioxidant
      enzymes (AOE) in the mammary pathology typically observed in old female rats, we
      undertook to determine the relationship between pituitary hormones, AOE activity,
      and histopathological changes in the mammary gland of senescent rats carrying
      neoplastic and nonneoplastic mammary pathologies. Serum levels of several
      pituitary hormones were determined by RIA in young (five months) and senescent
      (33 months) Sprague-Dawley female rats. The activity of catalase (CAT) and
      superoxide dismutase (SOD) in mammary tissue from the senescent animals was also
      determined. Senescent rats showed higher levels of prolactin (PRL) (p < 0.01),
      thyroid-stimulating hormone (TSH) (p < 0.05) and follicle-stimulating hormone
      (FSH) (p < 0.01) than their young counterparts. In senescent females the main
      histopathological findings at mammary level were a marked hyperplasia and the
      presence of fibroadenomas. In this group there was a positive correlation between
      serum levels of PRL and the activity of mammary SOD (p < 0.05). There was also a
      positive correlation between serum levels of FSH and the activity of mammary CAT
      (p < 0.001). Young females, rendered moderately hyperprolactinemic by means of
      anterior pituitary grafts, showed clear proliferative changes in their mammary
      glands. Senescent rats carrying fibroadenomas were less hyperprolactinemic than
      those with mammary hyperplasia (p < 0.05). Our results provide additional support
      to the idea that PRL may be a physiological modulator of mammary SOD activity and
      suggest that FSH can possibly influence the activity of CAT in mammary gland.
      They also suggest that tumorigenesis but not hyperplasia in rat mammary gland may
      be associated with low mammary SOD and CAT activities.

PMID- 9193898
TI  - The influence of age and some inducers on UDP-glucuronyltransferase activity.
AB  - UDP-glucuronyltransferase (UDP-GT) activity was examined in male Wistar rats aged
      0.5, 1, 2, 4, 8, 12, 20, and 28 months. The rats were treated with phenobarbital
      (75 mg/kg, 72 and 48 h before death), beta-naphthoflavone or dexamethasone (40
      mg/kg and 20 mg/kg, respectively, for three days before death). Prior to
      decapitation the rats were fasted for 12 h. Hepatic microsomes were prepared
      according to the method of Dallner. UDP-GT activity was determined by the method
      of Burchell and Weatherill. p-Nitrophenol was used as an aglucone. UDP-GT
      activity decreased rapidly in the control rats aged from two weeks to four
      months. In the older control rats the activity tended to increase. Two-week-old
      rats treated with phenobarbital showed a slightly increased UDP-GT activity. In
      the older animals (up to one year) UDP-GT activity increased to 150% of the
      control value and stayed at this level in the remaining age groups. beta
      Naphthoflavone was a more potent inducer of UDP-GT than phenobarbital. The
      activity of beta-naphthoflavone-induced UDP-GT was low in the youngest rats. It
      was about 180% in two-month-old rats and reached 260% of the control value in
      eight-month-old rats. Although the activity decreased in the older rats, it still
      exceeded 200%. Dexamethasone did not affect UDP-GT activity. Only in two-week-old
      and two-month-old rats did we observe a slight increase in the activity of UDP
      GT.

PMID- 9193899
TI  - No effect of age on the dose requirement of thiopental in the rat.
AB  - With increasing human age (20-80 years), the electroencephalogram (EEG) dose
      requirement for the intravenous anesthetic thiopental decreases approximately 10%
      per decade of life. The goal of this study was to compare the dose required to
      attain isoelectric EEG in young (4-5 month) vs. aged (24-25-month) Fischer 344
      rats. One second isoelectricity was found to be an endpoint where minimal
      cardiorespiratory depression occurred. The effects of age, infusion rate, and
      repeated administration were examined in nine young and nine old rodents.
      Thiopental dose requirement increased with increasing infusion rates. Repeated
      administration at two-day intervals did not demonstrate tolerance to thiopental.
      No difference in thiopental dose requirement was detected in the young vs.
      elderly rats. In a separate group of five young and five old rats, thiopental
      plasma, brain, heart, and CSF concentrations were measured when five seconds of
      EEG isoelectricity was achieved: no consistent differences were noted. The rat
      may not be an appropriate model to investigate acute age-related anesthetic
      effects in humans, because cardiovascular changes with age are dissimilar between
      species.

PMID- 9193900
TI  - Change in heat loss as a part of adaptation to repeated cold exposures in adult
      and aged male C57BL/6J mice.
AB  - Previous studies have shown that adult mice increase cold-induced heat production
      as a result of repeated exposures to cold, but that aged mice do not. The
      objective of the present study was to investigate changes in heat loss during
      repeated cold exposures in adult and aged C57BL/6J mice. Mice were partially
      restrained for three hours at 6 degrees C, three times at one-week intervals. Dry
      heat loss was inferred from measurements of differential temperature between the
      incoming and outgoing air in the experimental chamber. During the first cold
      exposure, aged mice showed less heat loss (both total and adjusted for body
      temperature) than adult animals, suggesting greater peripheral vasoconstriction
      in aged mice. With repeated cold exposures, both age groups showed increased heat
      loss, but the aged mice showed greater increase of heat loss, so that by the
      third cold stress test, no significant differences in heat loss between adult and
      aged mice were observed. The increase of heat loss after repeated cold exposures
      in aged mice might reflect a lesser peripheral vasoconstriction, serving to
      reduce the possibility of tissue necrosis in the cold.

PMID- 9193901
TI  - The error catastrophe theory of aging. Point counterpoint.

PMID- 9193902
TI  - Writer questions the inevitability of FPs' declining role in inpatient care.

PMID- 9193903
TI  - Conservatism and residents' availability in clinic.

PMID- 9193904
TI  - Ambulatory-based training of family physicians is needed.

PMID- 9193905
TI  - Building organizational consensus.

PMID- 9193906
TI  - Have our recruiting efforts distracted us from our teaching mission?

PMID- 9193907
TI  - Working with students not interested in family practice.

PMID- 9193908
TI  - Anatomy of a resident's research project.

PMID- 9193909
TI  - Variations in functional status among different groups of elderly people.
AB  - BACKGROUND: Functional status differs among populations of elderly, although the
      extent of differences in types of functions among groups has not been closely
      examined. This study identifies and compares characteristics among different
      populations of elderly, using a screening test that measures self-assessment of
      multiple areas of function. The screening tool used was the Dartmouth COOP
      Charts, developed for and primarily tested in office medical practices. It has
      not been used to systematically compare office patients with other groups of
      elderly. METHODS: Dartmouth COOP Charts were administered to five groups of
      elderly drawn from convenience samples of individuals age 65 and older, including
      elderly living in senior apartments, those attending community activities,
      mentally oriented nursing home patients, office patients, and elderly patients
      not visiting the doctor within the past 6 months. Demographic data, as well as
      COOP chart results, were obtained. RESULTS: There were multiple differences in
      COOP chart scores among the samples of elderly individuals. The greatest
      differences were in self-reported physical fitness and in the level of difficulty
      in performing daily activities. Medical office patients not visiting in 6 months
      had the highest fitness levels. On the other hand, the "social support"
      availability scale showed no differences among groups. Results from other scales
      were intermediate among these extremes. CONCLUSIONS: Different samples of elderly
      yield varying results on several measures of reported physical and emotional
      health. All convenience samples of the elderly may have somewhat poorer health
      than the average person age 65 and older. Of the groups studied, those with the
      poorest function were either older adults in nursing homes or those visiting the
      doctor's office for treatment.

PMID- 9193910
TI  - The effect of cognitive status on outcomes following rehabilitation.
AB  - BACKGROUND AND OBJECTIVES: Impaired cognition is a determinant of poor recovery
      following a hip fracture. Because of the risk of poorer outcomes, individuals
      with impaired cognitive function may be refused admission into a rehabilitation
      program. This study considered the impact of cognitive status on functional
      ability over time for older adults who participate in a rehabilitation program.
      METHODS: We studied a convenience sample of 200 consecutive patients who
      participated in an inpatient rehabilitation program following an orthopedic
      event. We obtained complete follow-up data on 181 participants. Baseline data
      were collected within 48 hours of admission and included demographics,
      rehabilitation diagnosis, living location prior to admission, the Mini-mental
      State Examination, and the Barthel Index (BI). Telephone follow-up was made at 3,
      6, and 12 months after discharge from rehabilitation, and we obtained information
      about demographic data and functional status (BI). RESULTS: There were no
      differences in the demographic characteristics of the two groups except for race;
      a larger percentage of African-Americans were in the impaired group. There was a
      statistically significant main effect of time with functional ability of all
      participants, increasing over the 12-month follow-up period. CONCLUSIONS: This
      study suggests that rehabilitation of the older adult, both with and without
      cognitive impairment, can result in improvement in functional ability that is
      sustained over a 12-month period. Although the findings indicate that those with
      cognitive impairment have lower functional performance at each testing period,
      these individuals improved functionally during the course of rehabilitation and
      maintained their discharge level of functioning for 1 year after discharge.

PMID- 9193912
TI  - Resident partnerships: an effective strategy for training in primary care.
AB  - BACKGROUND AND OBJECTIVES: To facilitate resident training in the ambulatory
      setting, a few family practice residency programs use a partnership system to
      train residents. Partnerships are pairs of residents from the same year that
      rotate together on inpatient services. We identified and characterized the
      advantages and disadvantages of partnership programs in family practice
      residencies. METHODS: We conducted a national survey of family practice
      residencies, followed by phone interviews with residency directors of programs
      with partnerships. RESULTS: A total of 305 of 407 (75%) residencies responded; 10
      programs fit our definition of partnership. Program directors were positive about
      resident partnerships. Benefits included improved outpatient continuity, enhanced
      medical communication skills, and emotional and intellectual support.
      Disadvantages were decreased inpatient exposure and difficulty coordinating
      residents' schedules. CONCLUSIONS: Directors were favorable about partnerships,
      which seem to be an underutilized technique to improve residency training.

PMID- 9193911
TI  - Assessing function in the elderly: is it mainstream?

PMID- 9193913
TI  - A fellowship in rural family medicine: program development and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Many strategies have been used by academic
      institutions to address the shortage of rural family physicians. Fellowship
      training in rural family medicine represents one approach. METHODS: Tacoma Family
      Medicine developed a fellowship program of this type. Five years of operations
      are described, including applicants, educational outcomes, rural outcomes, and
      adverse outcomes. RESULTS: An adequate applicant pool does exist, composed of
      both applicants from residency and from practice. A curriculum of advanced
      obstetrics, electives, and a rural experience has been successful. Unforeseen
      problems included a strained relationship with family practice residents in the
      program and competition for community preceptors. CONCLUSIONS: Family practice
      residencies with a mission of rural training are encouraged to consider the
      strategy of a rural fellowship.

PMID- 9193914
TI  - Standardized examination performance and specialty choice.
AB  - BACKGROUND AND OBJECTIVES: It has been suggested that medical students who attend
      schools known for graduating prospective primary care physicians may enter
      primary care residencies, rather than non-primary care residencies, because they
      are unable to compete for subspecialty residencies due to poorer academic
      performance. This study determined if performance on standardized examinations
      conducted by the National Board of Medical Examiners (NBME) could differentiate
      between students who selected primary care and those who selected non-primary
      care specialties at a medical school in the southeastern United States committed
      to graduating primary care physicians. METHODS: We examined initial scores on
      NBME examinations and subsequent residency selections by 780 students over a 14
      year period to determine if there were differences in the kind of residency
      placements of students who passed and those who failed the examinations. RESULTS:
      Data analysis indicated that medical students who entered primary care and non
      primary care residencies were not distinguishable on the basis of standardized
      examination performance. CONCLUSIONS: These results may help to refute negative
      stereotypes about students who enter primary care residencies and about medical
      schools known for promoting careers in primary care.

PMID- 9193915
TI  - Differences between diabetic patients who do and do not respond to a diabetes
      care intervention: a qualitative analysis.
AB  - BACKGROUND AND OBJECTIVES: We designed a qualitative case study to ascertain
      whether attitudes and views of diabetes differ between patients with diabetes who
      do and do not respond well to a diabetes care intervention. METHODS: Prospective
      epidemiological data were used to classify and sample graduates from an
      outpatient diabetes care program into one of two groups: 1) positive responders
      (n = 18) who had a 20% or greater improvement in glycemic control 6 months after
      the care program and 2) negative responders (n = 16) who had less than a 20%
      improvement in glycemic control 6 months after the care program. We collected
      data using depth interviews and focus groups. Transcriptions were summarized and
      analyzed using an editing approach. The themes from these two groups were
      summarized and compared to ascertain similarities and differences in attitudes
      and views of diabetes. RESULTS: Four major themes emerged from the analysis.
      Positive and negative responders differed a) in their views of diabetes and its
      treatment, b) on how they incorporated diabetes care into their daily routines,
      c) in "conversion experiences" in which some patients became suddenly much more
      aware of the serious threat of diabetes to their health, and d) in their views of
      their medical care providers. CONCLUSIONS: The conversion experiences observed in
      many of these subjects are not consistent with stage-of-change models of health
      related behavior change. These data advance our understanding of patients'
      diabetes-related attitudes and behaviors and may be used by clinicians to monitor
      change in patients' attitudes and expectations over time and by researchers to
      develop and target novel patient-centered clinical interventions to improve
      patient satisfaction and clinical outcomes.

PMID- 9193916
TI  - Are individuals with mental retardation at high risk for chronic disease?
AB  - BACKGROUND AND OBJECTIVES: Family physicians are responsible for the health and
      illness care of individuals with mental retardation (MR) in many community
      practices. Therefore, it is important to determine the special disease patterns
      for this group. This study determined if individuals with MR are at increased
      risk for selected chronic diseases. METHODS: We analyzed 366 individuals, living
      in the community, with a primary diagnosis of MR. The two comparison groups
      without MR were 427 individual Medicaid recipients and 746 privately insured
      individuals. RESULTS: Individuals with MR had higher rates of neurophysical
      conditions (eg, seizures, central nervous system conditions, and sensory loss)
      compared to the other two groups. However, they had lower rates of some chronic
      conditions and health behaviors (eg, hypertension, migraines/chronic headaches,
      diabetes, depression or anxiety, obesity, substance abuse, and smoking) compared
      to other Medicaid and insured patients. CONCLUSIONS: Individuals with MR have
      lower rates of many chronic conditions, compared with other Medicaid recipients.
      This finding should reduce concerns among family physicians that treatment of
      this special population involves higher rates of chronic illness.

PMID- 9193917
TI  - Faculty development for foreign teachers of family medicine.
AB  - BACKGROUND: The development of family medicine in Latin America is inhibited by
      limited resources. Successful strategies to promote the specialty include
      academic exchanges between countries. Short-term faculty development
      opportunities are needed for foreign academic family physicians. METHODS: After 2
      years of unstructured visits by Latin American physicians planning to teach
      family medicine, we designed a faculty development course, in Spanish, that
      continues to evolve through constructive feedback. This includes workshops in
      project planning, computer training, clinical decision making, family systems,
      clinical teaching, problem-based learning, and clinical epidemiology. Each fellow
      designs a project to be implemented subsequently in the country of origin.
      RESULTS: Since 1991, we have trained 37 physicians from nine Latin American
      countries, 27 since 1993 in the structured course. A full schedule encourages
      fellow to complete course objectives within 8 weeks. All participating physicians
      have rated highly the course content and quality. Twenty-five of the 27 course
      participants are or will soon begin teaching in family practice residency
      programs in their home countries. CONCLUSIONS: This faculty development course
      for Latin American physicians is perceived as an effective way to enhance
      academic skills. Ongoing evaluation will show how the fellowship impacts the
      physicians' teaching effectiveness and the development of family medicine in
      their countries.

PMID- 9193918
TI  - Phase three of academic family medicine.

PMID- 9193919
TI  - Aquatic pollution-induced immunotoxicity in wildlife species.
AB  - The potential for chemicals to adversely affect human immunologic health has
      traditionally been evaluated in rodents, under laboratory conditions. These
      laboratory studies have generated valuable hazard identification and
      immunotoxicologic mechanism data; however, genetically diverse populations
      exposed in the wild may better reflect both human exposure conditions and may
      provide insight into potential immunotoxic effects in humans. In addition,
      comparative studies of species occupying reference and impacted sites provide
      important information on the effects of environmental pollution on the
      immunologic health of wildlife populations. In this symposium overview, Peter
      Hodson describes physiological changes in fish collected above or below the
      outflows of paper mills discharging effluent from the bleaching process (BKME).
      Effects attributable to BKME were identified, as were physiological changes
      attributable to other environmental factors. In this context, he discussed the
      problems of identifying true cause and effect relationships in field studies.
      Mohamed Faisal described changes in immune function of fish collected from areas
      with high levels of polyaromatic hydrocarbon contamination. His studies
      identified a contaminant-related decreases in the ability of anterior kidney
      leukocytes to bind to and kill tumor cell line targets, as well as changes in
      lymphocyte proliferation in response to mitogens. Altered proliferative responses
      of fish from the contaminated site were partially reversed by maintaining fish in
      water from the reference site. Peter Ross described studies in which harbor seals
      were fed herring obtained from relatively clean (Atlantic Ocean) and contaminated
      (Baltic Sea) waters. Decreased natural killer cell activity and
      lymphoproliferative responses to T and B cell mitogens, as well as depressed
      antibody and delayed hypersensitivity responses to injected antigens, were
      identified in seals fed contaminated herring. In laboratory studies, it was
      determined that rats fed freeze-dried Baltic Sea herring had higher virus titers
      after challenge with rat cytomegalovirus (RCMV) than rats fed Atlantic Ocean
      herring; perinatal exposure of rats to oil extracted from Baltic herring also
      reduced the response to challenge with RCMV. Keith Grassman reported an
      association between exposure to polyhalogenated aryl hydrocarbons and decreased T
      cell immunity in the offspring of fish-eating birds (herring gulls and Capsian
      terns) at highly contaminated sites in the Great Lakes. The greatest suppression
      of skin test responses to phytohemagglutinin injection (an indicator of T cell
      immunity) was consistently found at sites with the highest contaminant
      concentrations. Judith Zelikoff addressed the applicability of immunotoxicity
      studies developed in laboratory-reared fish for detecting altered immune function
      in wild populations. She presented data from studies done in her laboratory with
      environmentally relevant concentrations of metals as examples. Although the
      necessity of proceeding with caution when extrapolating across species was
      emphasized, she concluded that published data, and results presented by the other
      Symposium participants, demonstrate that assays similar to those developed for
      use in laboratory rodents may be useful for detecting immune system defects in
      wildlife species directly exposed to toxicants present in the environment.

PMID- 9193920
TI  - Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of
      Mechanistic and Pharmacokinetic Data.
AB  - A workshop entitled "Implementation of EPA Revised Cancer Assessment Guidelines:
      Incorporation of Mechanistic and Pharmacokinetic Data" was held in Anaheim,
      California, in 1996 at the 35th Annual Meeting of the Society of Toxicology
      (SOT). This workshop was jointly sponsored by the Carcinogenesis, Risk
      Assessment, and Veterinary Specialty Sections of the SOT. The thrust of the
      workshop was to discuss the scientific basis for the revisions to the EPA
      Guidelines for cancer assessment and EPA's plans for their implementation. This
      is the first revision to the original EPA guidelines which have been in use by
      EPA since 1986. The principal revisions are intended to provide a framework for
      an increased ability to incorporate biological data into the risk assessment
      process. Two cases were presented, for chloroform and triclioroethylene, that
      demonstrated the use of the revised guidelines for specific cancer risk
      assessments. Using these new guidelines, nonlinear margin of exposure analyses
      were proposed for these chemicals instead of the linearized multistage model
      previously used by the EPA as the default method. The workshop participants
      generally applauded the planned revisions to the EPA guidelines. For the most
      part, they considered that the revised guidelines represented a positive step
      which should allow for and encourage the use of biological information in the
      conduct of cancer risk assessments. Several participants cautioned however that
      the major problem with cancer risk assessments would continue to be the
      inadequacy of available data on which to conduct more scientific risk
      assessments.

PMID- 9193921
TI  - Lung tissue responses and sites of particle retention differ between rats and
      cynomolgus monkeys exposed chronically to diesel exhaust and coal dust.
AB  - Several chronic inhalation bioassays of poorly soluble, nonfibrous particles have
      resulted in an increased incidence of lung tumors in rats, no increase in lung
      tumors in Syrian hamsters, and inconsistent results in mice. These results have
      raised concerns that rats may be more prone than other species to develop
      persistent pulmonary epithelial hyperplasia, metaplasia, and tumors in response
      to the accumulation of inhaled particles. In addition, particle deposition and
      the rate of particle clearance from the lung differ between rats and primates, as
      does the anatomy of the centriacinar region. For these reasons, the usefulness of
      pulmonary carcinogenicity data from rats exposed to high concentrations of
      particles for quantitatively predicting lung cancer risk in humans exposed to
      much lower environmental or occupational concentrations has been questioned. The
      purpose of this investigation was to directly compare the anatomical patterns of
      particle retention and the lung tissue responses of rats and monkeys exposed
      chronically to high occupational concentrations of poorly soluble particles. Lung
      sections from male cynomolgus monkeys and F344 rats exposed 7 hr/day, 5 days/week
      for 24 months to filtered ambient air, diesel exhaust (2 mg soot/m3), coal dust
      (2 mg respirable particulate material/m3), or diesel exhaust and coal dust
      combined (1 mg soot and 1 mg respirable coal dust/m3) were examined
      histopathologically. The relative volume density of particulate material and the
      volume percentage of the total particulate material in defined pulmonary
      compartments were determined morphometrically to assess the relative amount and
      the anatomic distribution of retained particulate material. In all groups,
      relatively more particulate material was retained in monkey than in rat lungs.
      After adjustment for differences between rat and monkey controls, the coal dust-
      and the combined diesel exhaust and coal dust-exposed monkeys retained more
      particulate material than the coal dust- and the combined diesel exhaust and coal
      dust-exposed rats, respectively. There was no significant difference in the
      relative amount of retained particulate material between diesel exhaust-exposed
      monkeys and rats. Within each species, the sites of particle retention and lung
      tissue responses were the same for diesel soot, coal dust, and the combined
      material. Rats retained a greater portion of the particulate material in lumens
      of alveolar ducts and alveoli than monkeys. Conversely, monkeys retained a
      greater portion of the particulate material in the interstitium than rats. Rats,
      but not monkeys, had significant alveolar epithelial hyperplastic, inflammatory,
      and septal fibrotic responses to the retained particles. These results suggest
      that intrapulmonary particle retention patterns and tissue reactions in rats may
      not be predictive of retention patterns and tissue responses in primates exposed
      to poorly soluble particles at concentrations representing high occupational
      exposures.

PMID- 9193922
TI  - Pulmonary structural and extracellular matrix alterations in Fischer 344 rats
      following subchronic phosgene exposure.
AB  - Phosgene, an acylating agent, is a very potent inducer of pulmonary edema.
      Subchronic effects of phosgene in laboratory animals are not well characterized.
      The purpose of the study was to elucidate potential long-term effects on collagen
      and elastin metabolism during pulmonary injury/recovery and obtain information
      about the concentration x time (C x T) behavior of low levels of phosgene. Male
      Fischer 344 rats (60 days old) were exposed either to clean air or phosgene, 6
      hr/day: 0.1 ppm (5 days/week), 0.2 ppm (5 days/week), 0.5 ppm (2 days/week), and
      1.0 ppm (1 day/week), for 4 or 12 weeks. A group of rats was allowed clean air
      recovery for 4 weeks after 12 weeks of phosgene exposure. This exposure scenario
      was designed to provide equal C x T product for all concentrations at one
      particular time point except for 0.1 ppm (50% C x T). Phosgene exposure for 4 or
      12 weeks increased lung to body weight ratio and lung displacement volume in a
      concentration-dependent manner. The increase in lung displacement volume was
      significant even at 0.1 ppm phosgene at 4 weeks. Light microscopic level
      histopathology examination of lung was conducted at 0.0, 0.1, 0.2, and 1.0 ppm
      phosgene following 4 and 12 and 16 weeks (recovery). Small but clearly apparent
      terminal bronchiolar thickening and inflammation were evident with 0.1 ppm
      phosgene at both 4 and 12 weeks. At 0.2 ppm phosgene, terminal bronchiolar
      thickening and inflammation appeared to be more prominent when compared to the
      0.1 ppm group and changes in alveolar parenchyma were minimal. At 1.0 ppm,
      extensive inflammation and thickening of terminal bronchioles as well as alveolar
      walls were evident. Concentration rather than C x T seems to drive pathology
      response. Trichrome staining for collagen at the terminal bronchiolar sites
      indicated a slight increase at 4 weeks and marked increase at 12 weeks in both
      0.2 and 1.0 ppm groups (0.5 ppm was not examined), 1.0 ppm being more intense.
      Whole-lung prolyl hydroxylase activity and hydroxyproline, taken as an index of
      collagen synthesis, were increased following 1.0 ppm phosgene exposure at 4 as
      well as 12 weeks, respectively. Desmosine levels, taken as an index of changes in
      elastin, were increased in the lung after 4 or 12 weeks in the 1.0 ppm phosgene
      group. Following 4 weeks of air recovery, lung hydroxyproline was further
      increased in 0.5 and 1.0 ppm phosgene groups. Lung weight also remained
      significantly higher than the controls; however, desmosine and lung displacement
      volume in phosgene-exposed animals were similar to controls. In summary, terminal
      bronchiolar and lung volume displacement changes occurred at very low phosgene
      concentrations (0.1 ppm). Phosgene concentration, rather than C x T product
      appeared to drive toxic responses. The changes induced by phosgene (except of
      collagen) following 4 weeks were not further amplified at 12 weeks despite
      continued exposure. Phosgene-induced alterations of matrix were only partially
      reversible after 4 weeks of clean air exposure.

PMID- 9193923
TI  - Potentiation of organophosphorus-induced delayed neurotoxicity following phenyl
      saligenin phosphate exposures in 2-, 5-, and 8-week-old chickens.
AB  - Phenylmethylsulfonyl fluoride (PMSF), a nonneuropathic inhibitor of neurotoxic
      esterase (NTE), is a known potentiator of organophosphorus-induced delayed
      neurotoxicity (OPIDN). The ability of PMSF posttreatment (90 mg/kg, sc, 4 hr
      after the last PSP injection) to modify development of delayed neurotoxicity was
      examined in 2-, 5-, and 8-week-old White Leghorn chickens treated either one,
      two, or three times (doses separated by 24 hr) with the neuropathic OP compound
      phenyl saligenin phosphate (PSP, 5 mg/kg, sc). NTE activity was measured in the
      cervical spinal cord 4 hr after the last PSP treatment. Development of delayed
      neurotoxicity was measured over a 16-day postexposure period. All PSP-treated
      groups exhibited > 97% NTE inhibition regardless of age or number of OP
      treatments. Two-week-old birds did not develop clinical signs of neurotoxicity in
      response to either single or repeated OP treatment regimens nor following
      subsequent treatment with PMSF. Five-week-old birds were resistant to the
      clinical effects of a single PSP exposure and were minimally affected by repeated
      doses. PMSF posttreatment, however, significantly amplified the clinical effects
      of one, two, or three doses of PSP. A single exposure to PSP induced slight to
      moderate signs of delayed neurotoxicity in 8-week-old birds with more extensive
      neurotoxicity being noted following repeated dosing. As with 5-week-old birds,
      PMSF exacerbated the clinical signs of neurotoxicity when given after one, two,
      or three doses of PSP in 8-week-old birds. Axonal degeneration studies supported
      the clinical findings: PMSF posttreatment did not influence the degree of
      degeneration in 2-week-old chickens but resulted in more severe degeneration
      (relative to PSP only exposure) in cervical cords from both 5- and 8-week-old
      birds. The results indicate that PMSF does not alter the progression of delayed
      neurotoxicity in very young (2 weeks of age) chickens but potentiates PSP-induced
      delayed neurotoxicity in the presence of 0-3% residual NTE activity in older
      animals. We conclude that posttreatment with neuropathic or nonneuropathic NTE
      inhibitors, following virtually complete NTE inhibition by either single or
      repeated doses of a neuropathic agent in sensitive age groups, can modify both
      the clinical and morphological indices of delayed neurotoxicity. This study
      further supports the hypothesis that potentiation of OPIDN occurs through a
      mechanism unrelated to NTE.

PMID- 9193924
TI  - Canalicular retention as an in vitro assay of tight junctional permeability in
      isolated hepatocyte couplets: effects of protein kinase modulation and
      cholestatic agents.
AB  - A simple, fast method to evaluate acute changes of tight junctional permeability
      in isolated hepatocyte couplets is proposed. The method consists of the recording
      of the number of canalicular vacuoles able to retain the previously accumulated
      fluorescent bile acid analogue cholyl-lysyl-fluorescein (CLF), as visualized by
      inverted fluorescent microscopy, following acute exposure to the compounds under
      study. The method was validated by (i) making a systematic documentation of the
      effect on CLF retention of a variety of hormonal modulators (vasopressin and
      phorbol esters), as well as several cholestatic (taurolithocholic acid,
      cyclosporin A, and estradiol 17 beta-glucuronide) and hepatotoxic agents
      (menadione, A23187, and t-butyl hydroperoxide), all known to affect biliary
      permeability in intact liver, and (ii) carrying out a comparative analysis of the
      results obtained with those recorded using rapid canalicular access of
      horseradish peroxidase (HRP) as an alternative procedure. The compounds tested
      all decreased canalicular vacuolar retention of CLF in a dose-dependent manner.
      Vasopressin- and phorbol ester-induced decline in CLF retention were prevented by
      pretreatment with the protein kinase C inhibitors H-7 and staurosporine, thus
      confirming a role for this enzyme in canalicular permeability regulation. A
      significant direct correlation (r = 0.934, p < 0.001) was obtained when the
      decrease in canalicular retention of CLF was compared with the increment in the
      canalicular access of HRP. Image analysis revealed that cellular fluorescence was
      not increased following exposure to these compounds, suggesting a paracellular
      rather than transcellular route for CLF egress. These results all support
      canalicular vacuolar retention of CLF as a suitable method to readily evaluate
      acute changes in tight junctional permeability in isolated hepatocyte couplets
      induced by physiological modulators or hepatotoxic agents.

PMID- 9193925
TI  - Chloroform in drinking water prevents hepatic cell proliferation induced by
      chloroform administered by gavage in corn oil to mice.
AB  - Chloroform administered by gavage in corn oil, but not when administrated in
      drinking water, has been shown to induce liver cancer in female B6C3F1 mice and
      to enhance cell proliferation. Since humans are exposed to chloroform in their
      drinking water, we evaluated whether exposure by this route would interact with
      the activity of chloroform when administered by gavage in corn oil. Female B6C3F1
      mice were exposed to chloroform in drinking water for 33 days at 0, 300, or 1800
      ppm (Experiment 1) or for 31 days at 0, 120, 240, or 480 ppm (Experiment 2) and
      for 3 days prior to termination also received a daily dose of 263 mg/kg
      chloroform administered by gavage in corn oil. Exposure to chloroform in drinking
      water reduced both the hepatotoxicity and the enhanced cell proliferation
      (bromodeoxyuridine-labeling index and mitotic index) elicited in response to
      chloroform administered by gavage in corn oil. Hence, chloroform administered in
      drinking water reduced the activity of chloroform administered by gavage in corn
      oil, suggesting that it would also reduce the hepatocarcinogenic activity of
      chloroform administered by gavage.

PMID- 9193927
TI  - Effect of administration of malathion for 14 days on macrophage function and mast
      cell degranulation.
AB  - Previous studies have shown that acute, oral administration of malathion
      modulated the humoral immune response to T-cell-dependent antigen, mitogenic
      responses, macrophage function, and mast cell degranulation. While administration
      of malathion for 14 days did not affect the generation of an immune response to
      antigen, it was possible that macrophage and mast cell functions were affected.
      In this report, the effect of malathion administration for 14 days upon these
      parameters were assessed. This treatment regimen increased the respiratory burst
      capacity to a maximal level at a dose of 1 mg/kg/day or greater. The effect of
      oral administration of malathion for 14 days on the degranulation of mast cells
      in various organs (heart, skin, and small intestine) and peritoneal lavage fluid
      was also assessed. At doses of 1 mg/kg/day and above, the number of mast cells
      that was undegranulated decreased and the number that was severely degranulated
      increased. There was no change in mast cell integrity in biopsies from heart and
      skin, and in peritoneal fluid after 14-day administration of 0.1 mg/kg/day.
      However, the number of mast cells associated with the small intestine that had
      undergone degranulation was increased at this dose of malathion. These data
      indicate that repeated administration of malathion increased macrophage function
      at doses as low as 1 mg/kg/day and led to mast cell degranulation at doses as low
      as 0.1 mg/kg/day.

PMID- 9193926
TI  - Modulation of the inflammatory effects of inhaled ozone in rats by subcutaneous
      prolactin-secreting, pituitary-derived tumors.
AB  - Rats are more sensitive to ozone-induced pulmonary inflammation and damage during
      late pregnancy and throughout lactation than in pre- or early pregnancy or
      postlactation. This window of sensitivity coincides with a period of elevated
      levels of pituitary-derived prolactin or placental lactogen. In this study, we
      investigated the hypothesis that prolactin exerts an enhancing effect on ozone
      induced pulmonary inflammation and damage, thus presenting a plausible
      explanation for the sensitivity profile observed in rats. Hyperprolactinemia was
      achieved by using rats with subcutaneous tumors that were derived from the MMQ
      tumor model previously described by Adler and co-workers (Adler, R. A., Krieg, R.
      J., Farrell, M. E., Deiss, W. P., and MacLeod, R. M., Metabolism 40, 286-291,
      1991). A variant of the MMQ tumor, the MMQr tumor, which appeared spontaneously
      from a single passage of MMQ tumor tissue, produced elevated levels of
      corticosterone in addition to high levels of prolactin. These two subcutaneous
      tumors had markedly different effects on adrenal, thymus, and spleen weights
      because of the different hormonal milieu they generated. There was also a
      significant difference between MMQ- and MMQr-bearing rats in their inflammatory
      response to acute ozone exposure as assessed by polymorphonuclear leukocytes
      (PMNs) in the airways. Rats with MMQ tumors were not significantly different from
      non-tumor-bearing controls in their baseline level of airway PMNs and PMN
      inflammation following ozone exposure, whereas MMQr-bearing rats had
      significantly elevated baseline PMNs in their airways and a greater PMN response
      to inhaled ozone. The hormonal milieu and elevated PMNs in the airways of both
      unexposed and ozone-exposed rats with MMQr tumors were similar to levels observed
      in lactating rats. The role of corticosterone in pulmonary inflammation in this
      model was investigated further by treating MMQ tumor-bearing rats with
      dexamethasone. Dexamethasone was effective in producing changes in organ weights
      similar to those observed in MMQr rats, but did not elicit higher airway PMN
      concentrations in unexposed rats as observed in the MMQr rats. We conclude that
      in this animal model prolactin did not significantly elevate airway PMN
      inflammation induced by ozone, and supplementation with exogenous glucocorticoid
      did not duplicate the endogenous airway PMNs numbers observed in MMQr-bearing
      rats or lactating rats.

PMID- 9193928
TI  - Manometric evaluation of defecation disorders: Part II. Fecal incontinence.
AB  - Fecal incontinence is a silent affliction that often leads to self-imposed
      ostracism. For many years, a lack of understanding regarding its pathophysiology
      and a lack of empathy among many physicians has bedeviled this problem. However,
      during the last two decades, remarkable strides have been made, both in the
      evaluation and in the treatment of incontinence. These advances stem from the
      ability to perform a detailed and comprehensive assessment of anorectal
      physiology. Anorectal manometry has spearheaded this renaissance. Manometry is
      not a single test but consists of a series of measurements that include an
      assessment of anal sphincter function, rectal sensation, rectoanal reflexes, and
      rectal compliance. Electrophysiological assessments such as pudendal nerve
      terminal latency can provide additional information regarding neuromuscular
      integrity. Newer techniques such as vectography, saline continence test,
      impedance planimetry, and prolonged ambulatory anorectal manometry have added a
      new dimension to the overall assessment. Radiological tests such as defecography
      and anal endosonography can provide complimentary information. These tests of
      anorectal function have advanced immensely our understanding of the
      pathophysiological mechanisms that are responsible for fecal incontinence.
      Equipped with sound objective information, today, it is possible to treat most
      incontinent patients with novel treatments that include medical, biofeedback, or
      surgical therapies. This is the second article in a two-part evaluation of
      defecation disorders that discusses the manometric evaluation of fecal
      incontinence.

PMID- 9193929
TI  - Spastic disorders of the esophagus.
AB  - Spastic disorders of the esophagus are found in up to 50% of patients referred
      for manometry, therapy representing the most prevalent motility disorders in
      clinical practice. They share in common their manifestations of hypermotility,
      one of two principal types of esophageal motor dysfunction. Diffuse esophageal
      spasm is segregated from the nonspecific spastic disorders because of its
      demonstrated interference with bolus transit. However, the overlap among the
      spastic disorders in manifestation, course, and management is great; segregation
      of any disorder within this group is not of paramount importance. Spastic
      disorders, pain reproduction with provocative testing, and psychological
      abnormalities are coprevalent in patients with unexplained symptoms, but a cause
      effect relationship of the motor abnormalities with the other findings is not
      established. The physician's charge in determining the relevance of a spastic
      disorder to the clinical presentation and for creating a treatment plan is to
      establish a direct relationship of motor dysfunction with symptoms-a task that
      may require correlation of transit abnormalities with symptoms using tests other
      than manometry. A variety of treatment options, invasive and noninvasive, are
      available today for patients who have spastic disorders, and each is effective in
      appropriately selected candidates.

PMID- 9193930
TI  - Current approach to the surgical management of chronic pancreatitis.
AB  - The indications for surgical intervention in chronic pancreatitis are suspicion
      of malignancy, local complications, and intractable pain. Chronic pancreatitis is
      a risk factor for development of pancreatic carcinoma, and carcinomas may
      present, initially with a clinical picture of chronic pancreatitis. Local
      complications of chronic pancreatitis such as common bile duct or duodenal
      obstruction and enlarging or symptomatic pseudocyst also mandate surgical
      intervention. Thrombosis of the splenic vein with left-sided portal hypertension
      is common and associated with a 10% incidence of gastric variceal hemorrhage,
      which requires splenectomy. The role of surgery in the management of pain
      associated with chronic pancreatitis is to provide relief. When the pain
      interferes substantially with the patient's quality of life or narcotics are
      required for pain relief, surgical intervention is indicated. Other factors that
      should be incorporated in assessing the need for surgical intervention are
      malnutrition due to the inability to eat or malabsorption, the need for frequent
      hospitalization, and the inability to work. The operation selected for chronic
      pancreatitis should correct or deal with all structural abnormalities, provide
      long-term pain relief, have a low mortality and morbidity rate, minimize
      subsequent exocrine and endocrine insufficiency, and have results independent of
      abstinence from alcohol. No single operation can provide an optimal solution to
      the management of pain or these diverse complications of chronic pancreatitis.
      The operation chosen must be individualized to treat the patient's needs.

PMID- 9193931
TI  - Immunology of liver transplantation: clinical management aspects.
AB  - Orthotopic liver transplantation has developed into the treatment of choice for
      many patients who develop complications of end-stage liver disease. With
      improvements in surgical technique and overall survival since the inception of
      liver grafting, a major consideration in the longterm care of liver transplant
      patients has become the management of allograft rejection and immunosuppressive
      therapy. With an increasing number of patients having undergone successful
      transplantation in the community, practicing gastroenterologists will likely be
      called upon more frequently to render care to these patients. In this article,
      the immunobiology of transplantation and rejection is discussed with an emphasis
      placed on the T-cell-major histocompatibility complex interaction, cytokine
      stimulation, and adhesion molecule binding. Commonly used immunosuppressive
      medications and promising ones for the future are reviewed. Also, clinical
      aspects of the short- and long-term management of immunosuppression are explored.

PMID- 9193932
TI  - Colonic angiodysplasia.
AB  - Colonic angiodysplasia (AD) is an important vascular lesion responsible for
      approximately 6.0% of cases of lower gastrointestinal hemorrhage. Lesions are
      usually located in the right colon and, although the pathophysiology is unknown,
      most are probably acquired as the result of a degenerative process associated
      with aging. Diagnosis is usually made during colonoscopy, but angiography can be
      efficacious when hemorrhage is severe. Most patients with bleeding AD are treated
      by endoscopy. Various methods have been used (monopolar electrocoagulation,
      injection therapy, contact probes, and lasers) with acceptable safety and
      success. perforation of the right colon is the main concern, especially with
      monopolar electrocoagulation and the YAG laser. In clinical practice, contact
      probes are used most often, although this approach has not been well studied as
      treatment for colonic AD.

PMID- 9193934
TI  - Endoscopic ultrasound.
AB  - Endoscopic ultrasound is currently an accepted part of the clinical practice of
      gastroenterology. It is used to evaluate submucosal lesions, thickened gastric
      folds, and depth of gastrointestinal tumor penetration. As the capabilities of
      the instruments improve, their role in the practice of gastroenterology widens.
      This review is designed to update the practicing physicians on this rapidly
      evolving field, pertaining to instrumentation for endosonography, clinical
      indications for endosonography, and future directions.

PMID- 9193933
TI  - Antibiotics and pancreatitis.
AB  - Despite improvements in the general supportive care of patients with acute
      pancreatitis, the morbidity of infectious complications remains high and
      bacterial infections account for most deaths. The role of antibiotics in reducing
      infectious morbidity and mortality has been debated for decades because of a lack
      of supportive clinical data. Research completed over the past decade has helped
      to define the microbiology, establish the risk factors, and improve the
      understanding of the pathogenesis of infectious complications in patients with
      acute pancreatitis. Patients with acute necrotizing pancreatitis are at the
      greatest risk of developing an infection with enteric gram-negative or gram
      positive bacteria translocated from the bowel lumen into the necrotic pancreatic
      tissue. The most effective antimicrobial agents are the fluoroquinolones,
      imipenem-cilastatin, and metronidazole, which achieve adequate penetration into
      pancreatic juice and necrotic tissue and inhibit the growth of enteric bacteria.
      Animal and human studies support the use of antibiotics for the prevention of
      infectious morbidity and mortality in severe acute pancreatitis. Recent clinical
      trials have assessed the role of both systemic antibiotic prophylaxis and
      selective bowel decontamination with nonabsorbable oral antimicrobials in high
      risk patients with acute necrotizing pancreatitis. This article provides an
      overview of our current knowledge of pancreatic infections and a critical
      analysis of studies on the role of antibiotics in this disease.

PMID- 9193936
TI  - Morphological and molecular characteristics of living human fetuses between
      Carnegie stages 7 and 23: ultrasound scanning and direct measurements.
AB  - The developmental age of an embryo in the first trimester of pregnancy is
      generally determined by ultrasound scanning and/or by calculation from menstrual
      age. In the original studies, validation of the estimate of gestational age by
      ultrasound was not possible as the exact date of conception was unknown.
      Variation in growth rates of identically aged fetuses has previously been
      reported after assisted conception and with the use of ultrasound scanning. As
      these pregnancies were ongoing the accuracy of the scanning results could not be
      determined. Comparison of scanning and direct measurements after termination of
      pregnancy and menstrual age were carried out to determine the accuracy in fetal
      dating. The results suggest that the use of ultrasound scanning to determine
      gestational age is of less use than previously thought, and that the use of
      menstrual age is severely limited.

PMID- 9193935
TI  - Morphological and molecular characteristics of living human fetuses between
      Carnegie stages 7 and 23: developmental stages in the post-implantation embryo.
AB  - Determination of embryonic age groups or stages has been based on the Carnegie
      Institute collection started in 1887. Improved technology has enabled the
      building of a new collection of embryos of < 9 weeks gestation; these were then
      used to compare with the original Carnegie collection. The results suggest that
      in providing definitive stages that are rigidly bound by developmental events,
      limitations are placed on categorizing the embryo. Allocation of embryos to a
      specific stage can assist in identifying post-ovulatory age but overlaps between
      stages could lead to classification into an incorrect stage.

PMID- 9193937
TI  - Morphological and molecular characteristics of living human fetuses between
      Carnegie stages 7 and 23: immunolocalization of inhibin alpha and beta a
      subunits.
AB  - Transforming growth factor (TGF) is known to have the ability to modify mitogenic
      responses of tissues to other peptide growth factors and therefore may contribute
      to the rapid growth rate of an embryo. Throughout the TGF superfamily there is a
      similar fundamental molecular architecture. Included in this superfamily are
      inhibin A, activin A and activin B. It has been shown that activin is a powerful
      mesodermal inducing factor in the early embryo. The human embryo has shown
      localization of inhibin in the gonads after 16 weeks gestation but it has not
      been previously identified in earlier embryos. The inhibin-activin protein was
      found in a range of tissues including the liver stages 19-21 (alpha) and stages
      19-22 (beta); oesophagus stages 19-22 (alpha and beta); stomach stages 21 and 22
      (alpha and beta); gut stages 16-22 (alpha) and 21 and 22 (beta); pericardium
      stages 12-22 (alpha and beta); gonad stages 21 and 22 (beta) stage 22 (alpha);
      adrenal stages 19-22 (alpha and beta); urogenital system stages 21 and 22 (alpha
      and beta); yolk sac stage 12 (alpha and beta); mesenchyme stages 16-22 (alpha);
      surface ectoderm stages 13-22 (alpha) and stages 16-22 (beta a); notocord stages
      13-22 (beta) and stages 21 and 22 (alpha); nasal, trachea and bronchi stages 19
      22 (alpha and beta) leading to speculation of the role of both subunits.

PMID- 9193938
TI  - Morphological and molecular characteristics of living human fetuses between
      Carnegie stages 7 and 23: localization of inhibin mRNA alpha and beta a subunits
      by in-situ hybridization.
AB  - Localization of the mRNA alpha and beta a subunits of inhibin has previously been
      reported in the human gonads during the second trimester. Adrenal inhibin has
      also been reported in the second trimester for the alpha, beta a and beta b
      subunits. Investigations showing localization by in-situ hybridization during the
      first trimester have not been reported. The results have shown hybridization of
      the alpha and beta a subunits, throughout the period of development studied, in a
      variety of tissues including the dorsal and thoracic aortas and pericardium
      stages 13-22 (beta a subunit); liver stages 19-21 (beta a) and stages 21-22
      (alpha); mesonephos stages 21 and 22 (beta a); gonad stages (alpha and beta a);
      adrenal stages 19-22 (alpha); surface ectoderm stages 16-22 (beta a); mesenchyme
      stages 16-22 (beta a); amnion stages 13-16 (beta a); yolk sac stage 12 (alpha and
      beta a); cartilage stages 19-22 (beta a); and nasal proliferation stages 21 and
      22 (beta a). When compared with distribution of the protein subunits it was noted
      that more immunostaining activity was found, suggesting that that probes were not
      sufficiently sensitive enough to detect all levels of mRNA expressed. It can be
      surmised, therefore, that the lack of visual hybridization of the mRNA cannot
      preclude the possibility that it is not being translated within the tissue even
      though hybridization was not apparent.

PMID- 9193940
TI  - The same but different: the biology of Theileria sporozoite entry into bovine
      cells.
AB  - Theileria are important tick-transmitted protozoan parasites that infect wild
      Bovidae and domestic animals throughout much of the world. Much of our
      understanding of Theileria sporozoite invasion of bovine cells is based on work
      on T. parva, the causative agent of East Coast fever in cattle throughout east,
      central and southern Africa. Sporozoite entry involves a defined series of
      sequential but separable steps that differ in important details from the invasion
      process in other apicomplexans such as Plasmodium and Toxoplasma. While the
      morphological features of invasion are fairly well documented, the detailed
      biology of the individual steps is only now becoming clear. This review
      summarizes much of this recent work on the biology of sporozoite entry. In
      particular, recent studies on the role of Ca2+ and cell activation processes in
      sporozoite entry suggest that the initial sporozoite binding event triggers the
      mobilization of intrasporozoite Ca2+ and the activation of both kinase and G
      protein associated signalling processes in the parasite. These processes in turn
      regulate the invasive capacity of the sporozoite although the identity of these
      parasite molecules and how they contribute to the invasion process remain to be
      determined.

PMID- 9193941
TI  - Evidence for hybridisation between Paramacropostrongylus iugalis and P. typicus
      (Nematoda:Strongyloidea) in grey kangaroos, Macropus fuliginosus and M.
      giganteus, in a zone of sympatry in eastern Australia.
AB  - Specimens of Paramacropostrongylus iugalis and P. typicus, collected from eastern
      (Macropus giganteus) and western (M. fuliginosus) grey kangaroos in New South
      Wales and Queensland, were examined morphologically and electrophoretically at 4
      enzyme loci previously demonstrated to be diagnostic between the 2 species.
      Collections of P. iugalis from M. giganteus from outside the zone of sympatry of
      the 2 kangaroo species conformed electrophoretically and morphologically with
      previous studies. Within the zone of sympatry, the 2 nematode species were
      distinguishable electrophoretically, with most P. iugalis occurring in M.
      giganteus and all P. typicus occurring in M. fuliginosus. Some specimens of P.
      iugalis were identified in M. fuliginosus and, in both host species, nematodes
      were encountered with electrophoretic profiles intermediate between P. iugalis
      and P. typicus. The frequent occurrence in these specimens of heterozygotes
      suggested that the genetic barriers between the 2 nematode species were not
      complete and that genetic interchange (i.e. hybridisation) was occurring.

PMID- 9193942
TI  - An electrophoretic analysis of patterns of speciation in Cloacina clarkae, C.
      communis, C. petrogale and C. similis (Nematoda:Strongyloidea) from macropodid
      marsupials.
AB  - An electrophoretic study was conducted on Cloacina clarkae, C. communis, C.
      petrogale and C. similis based on 19 enzyme loci. C. communis was widely
      distributed in Macropus robustus, showing some genetic variation among
      populations but occasionally switching to other macropodid hosts (M. agilis, M.
      antilopinus). C. similis occurred in members of the Petrogale penicillata
      complex, Macropus dorsalis and Thylogale billardierii, but showed no evidence of
      genetic differentiation in spite of its occurrence in different host species and
      in geographically distinct regions of Australia. C. clarkae from Macropus eugenii
      was genetically indistinguishable from C. similis and was considered synonymous
      with it. C. petrogale occurred in a similarly diverse range of hosts and
      geographical regions to C. similis, but was represented electrophoretically as 4
      distinct genetic species, 1 in Petrogale assimilis, a second in P. lateralis
      purpureicollis, a third in Macropus parryi in Queensland and a fourth in M.
      eugenii in South Australia. Although the host and geographical ranges of C.
      similis and C. petrogale are analogous, the genetic uniformity of the former and
      diversity of the latter illustrate the incomplete understanding we have of the
      immediate causes of speciation in nematodes.

PMID- 9193943
TI  - Integument ultrastructure of Oestrus ovis (L.) (Diptera:Oestridae) larvae: host
      immune response to various cuticular components.
AB  - The nasal bot fly, Oestrus ovis, was investigated to establish which specific
      cuticular component is most immunogenic to infested sheep and how larval cuticle
      attains a protective role, if any, against the host immune system. To accomplish
      these goals, larval cuticle was extracted by a variety of agents and tested
      against immune sera from infested sheep and experimentally immunized rabbits. The
      cuticle substructure remaining after extraction was examined to localize various
      immunogenic components. O. ovis larval integument comprises an inner cellular
      layer, the epidermis, and an overlying cuticle layer. In 3rd instar larvae, the
      cuticle comprises 2 additional layers: the procuticle with numerous pore canals
      and the epicuticle which includes the wax canals. Three additional layers,
      altogether comprising the cuticulin layer, are present external to the
      epicuticle. The epicuticle is completed by apposition of an amorphous
      electrondense material extending for up to 1 micron in thickness. When fixed with
      ruthenium red, cuticle becomes heavily stained all along the epicuticular surface
      in larvae of all developmental stages. However, in 3rd instar larvae, ruthenium
      red deposits are restricted to the cuticulin layer alone. By gel electrophoresis,
      3rd instar larval cuticle is shown to contain a number of polypeptides ranging in
      molecular weight from 180 to 4.5 kDa. The number and relative concentration of
      low molecular weight polypeptides was shown to vary in relation to the extraction
      media employed. Cuticular fragments examined after extraction exhibit an altered
      ultrastructure. When tested by immunoblotting, the cuticular polypeptides most
      reactive against sheep antisera are in the range of 180-56 kDa. A similar
      reaction was also detected with sera from rabbits infested experimentally with O.
      ovis larvae. Results are interpreted in relation to differential polypeptide
      distribution within the larval cuticle and to accessibility of the host immune
      system.

PMID- 9193944
TI  - Variation in the egg cell forming region of Gyrodactylus kobayashii Hukuda, 1940
      (Monogenea:Gyrodactylidae).
AB  - The egg cell forming region of Gyrodactylus kobayashii from goldfish (Carassius
      auratus) is a thin nucleated cytoplasmic layer surrounding the developing egg
      cell (= oocyte). The cytoplasm contains numerous elougate membranes. As parasites
      age, the egg cell forming region becomes electron lucent. The apical membrane of
      the egg cell forming region becomes disrupted in places. A basal matrix is
      indistinct in new-born and young worms, becoming more evident as worms grow
      older. Numerous pits (= basal pits) are found along the basal plasma membrane of
      worms with a mature male system. These pits appear to be stable components of the
      membrane and resemble hemidesmosomes. Basal pits were co-incident with sperm in
      the egg cell forming region in 3 of 5 worms examined. The function of the basal
      pits of G. kobayashii could not be determined. It is postulated, however, that
      they either assist sperm to traverse the egg cell forming region to fertilize the
      egg cell or stabilize the egg cell forming region against damage by sperm
      traversing this layer. The egg cell forming region encloses a large egg cell and
      1 or more smaller differentiating egg cells. The ripening egg cell has a large
      nucleus and extensive cytoplasm. The cell has a thickened membrane. Large
      vacuoles and invaginations at the periphery of the egg cell appear to engulf
      cytoplasm of the egg cell forming region.

PMID- 9193945
TI  - Cholinergic, serotoninergic and peptidergic components of the nervous system of
      Haematoloechus medioplexus (Trematoda, Digenea), characterised by cytochemistry.
AB  - Cholinergic, serotoninergic and peptidergic neuronal pathways have been
      demonstrated in whole-mount preparations of the frog-lung digenean trematode,
      Haematoloechus medioplexus, using enzyme cytochemical methodologies and indirect
      immunocytochemical techniques in conjunction with confocal scanning laser
      microscopy. All 3 classes of neuroactive substance were found throughout both
      central and peripheral elements of a well-developed orthogonal nervous system.
      Peptidergic immunoreactivity was particularly strong, using antisera directed to
      native flatworm neuropeptides, neuropeptide F, and FMRF amide-related peptides
      (FaRPs), and there was significant overlap in the staining with that for
      cholinergic components. The serotoninergic system appeared quite separate, with
      the staining localised to a different set of neurons.

PMID- 9193946
TI  - Analysis of immunological cross-protection and sensitivities to anticoccidial
      drugs among five geographical and temporal strains of Eimeria maxima.
AB  - Two laboratory strains (USDA strain No. 68 isolated from the eastern shore of
      Maryland 15 years ago and a University of Guelph strain isolated from an Ontario
      broiler house 23 years ago) and 3 recent field strains of Eimeria maxima
      [isolated in Maryland (MD), North Carolina (NC) and Florida (FL)] were tested for
      their ability to induce cross-protective immunity and their sensitivities to a
      variety of anticoccidial compounds. To assess immunological cross-protection, 1
      day-old chicks were inoculated and subsequently challenged at 10 days of age,
      testing all possible combinations of initial inoculating (immunizing) and
      subsequent challenge strain. Six days post-challenge, chicks were killed and
      weight gains and lesion scores were determined and compared to sham inoculated
      and challenged, and sham challenged age-matched controls. The 2 laboratory
      strains and the NC strain were fully cross-protective against each other by both
      these measures. In contrast, the MD and FL strains induced complete protection
      only against the homologous strain. Reciprocally, no other strains protected
      chicks completely against the FL and MD strains. Drug sensitivity studies using
      10 different anticoccidial formulations at prescribed drug levels showed
      significant differences between the 2 laboratory strains and the 3 recently
      isolated field strains; more recent isolates from commercial broiler houses
      demonstrated complete or partial resistance to a wider range of anticoccidial
      compounds. No correlation was seen between cross-protection and sensitivities to
      anticoccidials.

PMID- 9193947
TI  - Inhibitory effect of heparin on red blood cell invasion by Theileria sergenti
      merozoites.
AB  - Theileria sergenti infection has been one of the most serious infectious diseases
      of cattle in Japan. A major component in the pathogenesis of T. sergenti is
      anaemia. The erythrocytic life-cycle, which is responsible for all of the
      clinical manifestations of T. sergenti infection, is initiated by invasion of
      bovine red blood cells (RBCs) by merozoites. Here we have focused on the effect
      of heparin, which has an inhibitory effect on RBC invasion by Plasmodium
      falciparum, and demonstrated for the first time that bovine RBC invasion by T.
      sergenti was inhibited by heparin. Further, analysis of this mechanism showed
      that bovine RBC agglutination, by purified T. sergenti merozoites, was inhibited
      by heparin and low molecular weight (LMW) heparin. Moreover, hemagglutination was
      inhibited by treatment of the merozoites with heparinase. These results suggest
      that merozoites have heparin-like molecules on their surface which may be one of
      the important factors for attachment to RBCs.

PMID- 9193948
TI  - Life-history variation among lines isolated from a laboratory population of
      Heligmosomoides polygyrus bakeri.
AB  - The extent of variation in several life-history traits within a laboratory
      population of the parasitic nematode, Heligmosomoides polygyrus bakeri, was
      studied in 10 relatively inbred parasite lines isolated from a stock population
      and characterized in BALB/c mice after 4, 8 and 11 generations of isolation. As
      expected, within-line variation for most traits at generation 11 compared to
      generation 4 significantly decreased (P < 0.01). At each generation of
      characterization, variation was observed among lines for parasite establishment,
      rate of development in the host, rate of early egg production, per capita
      fecundity, short-term and long-term survival and profiles of egg production, rate
      of decline in egg production, life-long reproductive effort and in vitro egg
      hatchability. Measures of all traits, except establishment, were highly
      repeatable. The rate of development was higher at generation 8 compared to the
      stock (P < 0.0001), and regression analysis revealed that early egg production of
      lines increased over 11 generations of isolation (P = 0.003). These results,
      together with the observed decrease (P < 0.01) in total variation of most of the
      traits over all lines during the process of isolation, suggested an evolutionary
      response of the traits, probably to the rapid passage of lines every month. The
      rate of development subsequently decreased between generations 8 and 11 in all
      lines (P < 0.0001), suggesting that the random genetic drift procedure used to
      isolate the lines eventually exerted detrimental inbreeding effects on this
      trait. The evolutionary responses of life-history traits to rapid passage and
      inbreeding suggest a genetic basis for variation in these life-history traits.

PMID- 9193949
TI  - Transmission dynamics of helminth parasites of pigs on continuous pasture:
      Oesophagostomum dentatum and Hyostrongylus rubidus.
AB  - An increase in alternative outdoor pig production systems is occurring in
      Denmark, and this study was designed to elucidate the transmission patterns of
      Oesophagostomum dentatum and Hyostrongylus rubidus in pigs allowed to graze
      continuously on a pasture. A group of pigs was turned out in May 1993 (Year 1 of
      the study) and subsequently inoculated with low numbers of both helminths. These
      pigs were followed parasitologically until October by serial necropsy and
      sampling of faeces, grass and soil. A non-inoculated group of pigs was similarly
      followed on the same pasture in Year 2 (1994). Pasture infectivity was measured
      using helminth-naive tracer pigs during all seasons. The pasture vegetation was
      rapidly destroyed by the pigs, resulting in a dirt lot by the autumn of Year 2.
      The area was soon contaminated with eggs, resulting in heavy pasture infectivity
      and increasing worm burdens in late summer; then the numbers of larvae declined
      markedly. In May of Year 2, newly exposed pigs became only lightly infected
      (mostly O. dentatum), and no transmission was observed in July-August of Year 2,
      probably due to an unusually dry summer and a lack of protecting vegetation. The
      results indicate that both O. dentatum and H. rubidus are very sensitive to
      environmental factors, because significant transmission occurred only under the
      most favourable conditions (summer combined with protecting vegetation as in Year
      1). Transmission was severely reduced during the low temperatures experienced in
      the winter between Years 1 and 2 and during the dry summer of Year 2, when
      vegetation was lacking. Continuous grazing actually reduced transmission of O.
      dentatum and H. rubidus because of the reduction in vegetation. This, however, is
      not a desirable alternative farming system, because of its adverse environmental
      effects. This environmental impact may be mitigated by employment of a pasture
      rotation system in place of continuous grazing.

PMID- 9193950
TI  - Transmission dynamics of helminth parasites of pigs on continuous pasture:
      Ascaris suum and Trichuris suis.
AB  - In Denmark, alternative outdoor production systems for pigs are becoming more
      frequent, and information on the transmission of Ascaris suum and Trichuris suis
      under continuously grazed pasture conditions is needed. A group of pigs was
      turned out on a pasture in May 1993 (Year 1 of the study), inoculated with 200
      eggs of A. suum and 1000 eggs of T. suis, and followed parasitologically. A non
      experimentally infected group of pigs was similarly turned out on the same
      pasture the following year (Year 2) and again followed parasitologically. Pasture
      infectivity was measured using helminth-naive tracer pigs. During the summer of
      Year 1, A. suum eggs became infective within 4-6 weeks on the pasture. However,
      transmission was moderate until August of Year 2, when a pronounced increase in
      transmission occurred. After 2 months on the pasture, the continuously exposed
      pigs in summer seasons of both Years 1 and 2 harboured small overdispersed
      populations of adult A. suum, moderate numbers of liver white spots, and high
      specific IgG responses. These parasitological measures on chronically exposed
      pigs did not, however, correlate well with pasture infectivity or with each
      other. In contrast, the liver inflammation and specific IgG responses (but not
      the intestinal A. suum burdens) of the tracer pigs were highly correlated (P =
      0.0001) and appeared to better reflect pasture infectivity. The inoculated pigs
      excreted T. suis eggs by the late summer of Year 1, but no transmission took
      place before August of Year 2. Thus, the T. suis population of infective eggs
      built up very slowly. The results indicate that T. suis eggs may survive for a
      considerable time, however. The study results reveal that A. suum and T. suis
      eggs are much more resistant to environmental factors than free-living infective
      larvae of pig parasites such as Oesophagostomum dentatum and Hyostrongylus
      rubidus. Control of these parasites in outdoor systems will present more
      difficult challenges than that for parasites transmitted by free-living larvae.

PMID- 9193952
TI  - Immunization of mice with ultraviolet-attenuated cercariae of Schistosoma mansoni
      transiently reduces the fecundity of challenge worms.
AB  - In the present study cohorts of ICR and BALB/c mice were immunized with u.v.
      irradiated cercariae of S. mansoni and challenged 5 weeks later, in parallel with
      unimmunized control mice, with approximately 100 cercariae. Total worm burdens at
      5, 6, 7 and 8 weeks after challenge were significantly reduced by 27-65% in
      immunized mice. The total number of eggs and the number of eggs/female worm
      trapped in liver and small intestine were reduced significantly at 6 and 7 weeks
      post challenge in immunized, as compared to unimmunized mice. Decrease in tissue
      egg load could be achieved in BALB/c mice passively transferred with spleen cells
      from u.v.-attenuated cercaria-immunized mice. The proportion of female worms
      laying eggs in vitro was diminished only in worms recovered from highly resistant
      mice. The reduction in worm oviposition in immunized mice was no longer apparent
      at 8 weeks. The data taken together indicate that highly effective immunization
      of outbred and inbred mice with attenuated cercariae leads to significant, but
      transient, impairment in challenge worm egg production.

PMID- 9193951
TI  - Inhibition of spleen cell proliferative response to mitogens by excretory
      secretory antigens of Fasciola hepatica.
AB  - The effect of Fasciola hepatica excretory-secretory antigen (ESA) on the
      proliferative response of spleen mononuclear (SpM) cells of normal rats to
      stimulation with mitogens has been examined. When ESA was added to normal SpM
      cells, there was a decrease in the proliferative response to concanavalin A (Con
      A) or lipo-polysaccharide (LPS) in a dose-dependent manner. The addition of
      indomethacin, which blocks prostaglandin synthesis, or N omega-nitro-L-arginine
      methyl ester (L-NAME) a specific inhibitor of nitric oxide (NO) synthase, had no
      effect on the ability of ESA to suppress the proliferative response to Con A.
      However, supplementation of the culture media with catalase, which degrades
      hydrogen peroxide (H2O2) or superoxide dismutase (SOD) to remove superoxide anion
      (O2), resulted in a restoration of proliferation to Con A. When LPS was used as
      mitogenic stimulus no inhibitor added to the culture restored the proliferation.
      These results suggest that H2O2 and O2- are involved in the suppressor phenomenon
      induced by ESA in the T-cell proliferative events.

PMID- 9193953
TI  - Low molecular weight Cooperia oncophora antigens. Potential to discriminate
      between susceptible and resistant calves after infection.
AB  - The recognition of low molecular weight proteins by sera obtained during a single
      oral (primary) infection with 100,000 3rd-stage Cooperia oncophora larvae was
      studied in calves. Three groups of 6 or 7 calves were selected based on different
      egg excretion patterns. SDS-gel electrophoresis of adult Cooperia antigen under
      reducing conditions, followed by Western blotting, revealed that resistance of
      individual calves to C. oncophora might be related with antibody responses (42
      days post infection) against at least 2 protein fragments (14-16 kDa and 27 kDa).
      The 14-16-kDa protein complex was bound, to some extent, by individual sera from
      all calves. The intensity of staining was negatively correlated with egg
      excretion on Day 42 p.i. Calves with high egg counts on Day 21 p.i. either did
      not or only weakly recognized the 27-kDa band. It has to be established whether
      the 14-16 kDa (or recombinant 14.2 kDa) provides a tool for immunodiagnostics and
      whether the 27-kDa fragment can help further unravel immune-mediated resistance
      to Cooperia.

PMID- 9193954
TI  - H-2 genes and resistance to infection with Heligmosomoides polygyrus in
      selectively bred mice.
AB  - Two lines of mice bred selectively for high resistance (RH) and susceptibility
      (SL) to reinfection with Heligmosomoides polygyrus demonstrated disparate levels
      of resistance to infection but did not differ in the frequency of H-2 antigens
      when assayed with antisera against antigens of 5 inbred H-2 haplotypes. The
      selected RH and SL mice were crossbred with, and backcrossed to, the inbred CBA
      mice. F1 mice from crosses between RH and CBA were as resistant to reinfection
      with H. polygyrus as their RH parents. F1 mice from crosses between SL and CBA
      were more resistant than either of their parents. BC1 mice were either positive
      or negative for H-2 antigens from RH and SL mice. BC1 mice that were positive for
      RH H-2 antigens were more resistant to infection than their negative littermates,
      but they were significantly more susceptible to infection with H. polygyrus than
      their F1 parents. These results demonstrated that genes within and mapped outside
      H-2 complex control the level of resistance to H. polygyrus in the selected mice
      and suggested that selective breeding of mice for resistance fixed the relevant
      genes in and outside the H-2 complex.

PMID- 9193955
TI  - Molecular delineation of Cylicocyclus nassatus and C. ashworthi
      (Nematoda:Strongylidae).
AB  - The nucleotide sequences of the first internal transcribed spacer (ITS-1), 5.8S
      gene and second internal transcribed spacer (ITS-2) of ribosomal DNA have been
      determined for Cylicocyclus nassatus, C. ashworthi and C. insignis. Pairwise
      comparisons revealed sequence differences between the taxa ranging from 3.8 to
      6.2% for the ITS-2 and 2.2-2.7% for the ITS-1. For the ITS-1, the level of the
      sequence difference between C. ashworthi and C. nassatus (2.2%) was equivalent to
      that between C. nassatus and C. insignis (2.2%), indicating that C. ashworthi and
      C. nassatus represent separate species. Theoretical restriction maps were
      constructed from the sequence data, and a polymerase chain reaction-linked
      restriction fragment length polymorphism (PCR-linked RFLP) technique was
      established to unequivocally distinguish C. ashworthi from C. nassatus.

PMID- 9193956
TI  - The adhesive attitude of the gill-parasitic ancyrocephaline monogenean
      Bifurcohaptor indicus.
AB  - Most specimens of the ancyrocephaline monogenean Bifurcohaptor indicus attach
      themselves to the afferent border of the primary gill lamella of their host
      Mystus vittatus so that the body lies between the hemibranchs of the gill. The
      parasite uses 2 greatly enlarged dorsal hamuli like a pair of forceps to grasp
      the edge of the lamella. The ventral body surface of most individuals is directed
      towards the proximal end of the lamella.

PMID- 9193957
TI  - Social relationships in later life: a review of the research literature.
AB  - This review examines the contribution of sociological perspectives to the study
      of relationships in later life. Three main areas are analysed: first, the family
      life of older people, second, marital relationships; third, friendship in later
      life. The article concludes with an assessment of the changes affecting the
      social lives of different groups of older people.

PMID- 9193958
TI  - Depression in dementia: a study of mood in a community sample and referrals to a
      community service.
AB  - The association between degree of cognitive impairment and severity of depressive
      symptoms was examined in a randomly selected community-based sample of elderly
      people and in a sample of patients referred to an old age psychiatry service.
      Findings contradict previous reports of less cognitive impairment in demented
      patients with depressive symptoms. We suggest that sample selection bias has
      contributed to the earlier reports.

PMID- 9193959
TI  - The use of selective serotonin reuptake inhibitors for depression and psychosis
      complicating dementia.
AB  - This retrospective chart review examines the impact of selective serotonin
      reuptake inhibitors on 20 patients with both depression and psychosis
      complicating dementia of the Alzheimer type (DAT) and other dementias. Fifteen of
      the 20 patients had moderate to marked improvement in depressive and psychotic
      symptoms. Eleven of 12 patients with DAT had moderate to marked improvement
      compared to only four of eight patients with dementia from other causes. The
      drugs were effective in diminishing or eliminating psychotic symptoms in six
      patients who had previously not responded to a trial of a neuroleptic. The
      selective serotonin reuptake inhibitors may have an important role to play in
      patients with DAT who have coexisting depression and psychosis. These drugs are
      very well tolerated and may have a place as first-line agents in non-emergent
      settings where a clinician might otherwise think of instituting a neuroleptic or
      as a second-line agent when a neuroleptic has proven ineffective.

PMID- 9193961
TI  - Psychiatric disturbances and the use of psychotropic drugs in a population of
      nonagenarians.
AB  - The present study examined the prevalence of dementia, anxiety syndromes,
      depression, psychotic symptoms, sleep disturbance and the use of psychotropic
      drugs in a population of 330 nonagenarians. Subjects underwent an extensive
      medical examination, and information on sociodemographic characteristics, mental
      health, physical health and psychotropic drug use was collected. The prevalence
      of dementia in the study sample was 46.7% according to DSM-III-R criteria.
      Demented persons had more often psychotic symptoms (11.7% versus 3.4%) and
      anxiety syndromes (5.2% versus 1.1%) than non-demented. Depression was equally
      prevalent in both the demented and non-demented (8.4% versus 7.4%), whereas sleep
      disturbance was a more common complaint in non-demented persons. Half of the
      study sample (49.7%) used some sort of psychotropic drug, with the most common
      being hypnotics and the least common being antidepressants. However, the rate of
      specific treatment was low, especially for depression, indicating the need for
      more knowledge concerning the recognition of depression in the very elderly.

PMID- 9193960
TI  - A comparison of the clock drawing test and the Pfeiffer Short Portable Mental
      Status Questionnaire in a geropsychiatry clinic.
AB  - Wolf-Klein and colleagues' clock drawing test (CDT) performance was compared with
      Pfeiffer's Short Portable Mental Status Questionnaire (Pfeiffer) scores in 145
      outpatient geropsychiatry patients. Although normal CDT results were almost
      always associated with normal Pfeiffer scores, 21% of Pfeiffer normal individuals
      drew abnormal clocks. Age, but not gender or education, was significantly
      associated with this finding. Almost all the Pfeiffer normal subjects who drew
      abnormal clocks were diagnosed with primary psychiatric disorders (85%) or
      neurologically based organic mood and anxiety disorders (12%); only one (3%) had
      dementia. We suggest the discrepant performance between the CDT and Pfeiffer may
      result from psychiatric illness. Contributing to this may be CDT sensitivity to
      executive skills dysfunction. This dyscontrol can occur in patients with dementia
      and other neurological disorders, but also presents in some primary mental
      disorders. Older age may heighten this impairment. In a typical geropsychiatry
      clinic, the CDT will not have high specificity for Alzheimer's disease as
      reported by Wolf-Klein and her colleagues. This results from the presence of many
      patients with primary psychopathology, some of whom will draw abnormal clocks,
      and a limited number with dementia-particularly Alzheimer's disease. Abnormal CDT
      results of geropsychiatry outpatients must therefore be interpreted carefully.
      Additional conclusions regarding the study results are discussed.

PMID- 9193962
TI  - Methodological issues in characterizing treatment response in demented patients
      with behavioral disturbances.
AB  - Despite the proliferation of instruments developed to rate behavioral
      disturbances associated with dementia, systematic studies of how ratings on these
      instruments should be analyzed to measure change in disruptive behaviors or
      distressing symptoms (ie treatment response) are noticeably absent. Using one of
      these scales, we compared three methods to characterize treatment response in 52
      elderly demented inpatients who participated in a standardized neuroleptic trial.
      While all three analyses identified a statistically significant improvement, they
      conveyed differently the clinical improvement experienced by the patients.
      Categorical outcomes communicated the clinical meaning of improvement better than
      changes in total score; changes in factor scores best revealed the differential
      impact of treatment on specific behavioral and symptomatic domains. Given the
      heterogeneity of the problematic behaviors and symptoms exhibited by demented
      patients included in treatment trials, regardless of the intervention being
      tested or of the instrument being used to rate behaviors, a focused approach to
      characterizing treatment response is needed.

PMID- 9193963
TI  - A comparison of older longstay psychiatric and learning disability inpatients
      using the Health of the Nation Outcome Scales.
AB  - OBJECTIVE: With increasing longevity, the number of elderly patients with
      psychiatric or learning disabilities is likely to increase. The degree of overlap
      of symptoms and needs of these two groups of patients, which may allow for their
      care within the same service, was examined. DESIGN: Twenty-six longstay, elderly
      (> 65 years) psychiatric patients resident in psychogeriatric wards of a
      psychiatric hospital were compared with 23 longstay, elderly patients and 40
      longstay patients aged 50-65 years, both resident in the wards of a specialist
      hospital for learning disabilities. The instrument used was the Health of the
      Nation Outcome Scales (HoNOS). RESULT: On the HoNOS, the elderly psychiatric
      patients scored significantly higher for problems with mood, relationships and
      occupation/activities. There were no significant differences for any of the
      scales rated between the 50-65 and > 65 years old patients with learning
      disabilities. CONCLUSION: The similarities between the three groups of patients
      would suggest that for some patients the same services may be utilized. This
      could reduce the cost of the care in the community and entail more economical use
      of the facilities and staff. The HoNOS proved to be a concise and simple
      instrument, which could become a useful tool in monitoring the outcome of
      healthcare in longstay patients.

PMID- 9193964
TI  - Outcome of clozapine therapy for elderly patients with refractory primary
      psychosis.
AB  - OBJECTIVE: The objective was to analyze outcome of clozapine therapy in elderly
      patients with treatment refractory primary psychosis. DESIGN: This was an open
      label clozapine trial in elderly patients. Patient psychopathology was assessed
      before and after clozapine therapy. SETTING: A psychiatry service at a large
      urban/suburban Veterans Administration Medical Center. PATIENTS: Inpatients and
      outpatients age 65 years or older with primary psychotic disorders established to
      be resistant to conventional antipsychotic therapy (Kane et al., 1988). Ten
      patients met study inclusion criteria out of a total of 134 patients receiving
      clozapine at the Cleveland VAMC (7.5%). Mean age of the group was 70.6 years.
      MEASURES: Patients were rated with the Brief Psychiatric Rating Scale (BPRS;
      Overall and Gorham, 1962). Additional data on patient demographics, comorbid non
      psychiatric diagnoses and concurrent psychotropic medication were collected via
      chart review. RESULTS: Mean clozapine dosage was 204 mg/day for a mean duration
      of 430 days. 7/10 patients had some degree of clinical improvement and 3/10
      patients had significant improvement documented by BPRS change of 20% or greater.
      Patients had a mean of 1.4 comorbid physical illnesses, which were not worsened
      by clozapine therapy. 4/10 patients discontinued clozapine therapy due to adverse
      effects or inability to comply with bloodwork; however; only 2/10 were truly
      treatment intolerant. CONCLUSIONS: Clozapine is a useful alternative treatment
      option for elderly individuals with refractory primary psychosis. As in younger
      patients, inability to tolerate drug-related adverse effects or weekly bloodwork
      may lead to drug discontinuation.

PMID- 9193965
TI  - Eating disorders in dementia.
AB  - OBJECTIVES: To examine the prevalence and associations of altered eating patterns
      in dementia sufferers. DESIGN: Prospective cohort study. SETTING: Psychiatric
      services and a memory clinic. SAMPLE: 124 patients with DSM-III-R dementia.
      MEASURES: The Geriatric Mental State Schedule, the History and Aetiology
      Schedule, the Cornell Depression Scale and the CAMCOG. Additional standardized
      questions were asked about eating patterns in the month prior to the study.
      RESULTS: Information concerning eating patterns was obtained from 105 of the 124
      patients: 21% had increased food consumption, 22.1% had decreased food
      consumption, 2.9% tried to eat inedible substances, 11.4% had an increased
      preference for sweet things, 7.6% became more fussy about their food choices and
      4.8% became less fussy. Decreased food consumption was significantly associated
      with less severe cognitive impairment and was related to RDC major depression in
      some patients. An increased preference for sweet things showed an association
      with a diagnosis of Alzheimer's disease. Increased food consumption was probably
      heterogeneous. Neither increased food consumption nor an increased preference for
      sweet foods was associated with the severity of cognitive impairment. CONCLUSION:
      Altered eating patterns are common in dementia sufferers.

PMID- 9193966
TI  - Time course of response to electroconvulsive therapy in elderly depressed
      subjects.
AB  - OBJECTIVE: To assess the time course of response to electroconvulsive therapy
      (ECT) in elderly depressed subjects. In particular, to determine whether
      significant antidepressant response occurs during the first few treatments.
      DESIGN: A naturalistic study of elderly patients receiving ECT. SETTING: Acute
      admission wards of a UK old age psychiatric service. PATIENTS: 13 consecutive
      inpatients aged over 65 years, meeting inclusion criteria, with a diagnosis of
      current major depressive episode, who were treated with ECT. MAIN OUTCOME
      MEASURES: Severity of depression as assessed by the Montgomery and Asberg
      Depression Rating Scale (MADRS), psychomotor speed as assessed by Gibson's spiral
      maze test (GSM) and the Kendrick digit copying test (KDCT). RESULTS: The first
      ECT treatment reduced the mean MADRS score by 21% (p < 0.0001) and the second
      treatment the mean MADRS was reduced by 36% (p < 0.0001). A non-significant
      improvement on GSM scores was seen that paralleled improvement in the MADRS. The
      average number of ECT treatments needed to reduce the MADRS score by half was
      3.73 +/- 1.85, though the actual number varied between 1 and 7. CONCLUSIONS: ECT
      is a highly effective treatment for depression in the elderly and significant
      antidepressant response can be demonstrated after only one treatment, arguing for
      careful mental state monitoring during treatment. However, considerable
      variability is seen in individual cases, implying that ECT should not be
      abandoned just because rapid response is not seen.

PMID- 9193968
TI  - A comparison of semantic memory in vascular dementia and dementia of Alzheimer's
      type.
AB  - OBJECTIVE: To determine whether semantic memory is impaired in vascular dementia
      and to assess the utility of semantic memory measures in differentiating vascular
      dementia from dementia of Alzheimer's type (DAT). DESIGN: Case-control study.
      PATIENTS: Ten patients with Cambridge Mental Disorders in the Elderly (CAMDEX)
      diagnosis of 'definite' mild or moderate vascular dementia (mean age 77) were
      individually matched with 10 patients with a CAMDEX diagnosis of 'definite' DAT
      on the basis of age, education, sex, premorbid IQ (as measured by the National
      Adult Reading Test) and performance on the Cambridge Cognitive Examination
      (CAMCOG). In addition, 10 age, sex and education matched volunteer or relative
      controls were assessed. OUTCOME MEASURES: A detailed semantic memory test battery
      consisting of five subtests: category fluency, picture naming, picture sorting,
      word-picture matching and generation of verbal definitions. RESULTS: Compared to
      normal controls, both patient groups were impaired on all subtests of the
      semantic battery with the exception of the word-picture matching test. No
      differences were found between the vascular dementia and DAT groups on any of the
      measures. CONCLUSIONS: Impairment of semantic memory is a feature of both
      vascular dementia and DAT. Tests of semantic memory appear, therefore, of little
      value in differentiating between these two major causes of dementia. Further work
      is required to determine whether the nature of the processing deficit is the same
      in these conditions.

PMID- 9193967
TI  - Psychotropic drug use and cognitive decline among older men and women.
AB  - This epidemiological study focuses on cognitive change related to psychotropic
      drug use in a population-based sample of subjects aged 65 and over. Cognitive
      functioning was assessed in 1982 and 1988 by the Short Portable Mental Status by
      Pfeiffer, and cognitive decline was defined as an increase of more than 2 errors
      in 1988 relative to the 1982 assessment. Psychotropic drugs were classified into
      benzodiazepines and non-benzodiazepines. For both medications, four patterns of
      intake were considered: no use reported at both interviews, continuous use at
      both interviews, temporary use at the 1982 interview and new use at the 1988
      interview. Depressive symptomatology was assessed by the Center for Epidemiologic
      Studies Depression Scale. The analysis was performed on 1200 subjects with no or
      minimal impairment at baseline for whom complete data were available. Univariate
      analyses showed cognitive decline associated with gender, level of education and
      new medical condition; it was also related to depressive symptomatology and
      psychotropic drug use. These two factors were the most strongly associated with
      decrease in performance in multivariate analyses. Cognitive decline differed
      according to class of psychotropic drugs and pattern of use: benzodiazepine
      temporary users exhibited a lower risk compared with never users (OR = 0.23, p =
      0.056), non-benzodiazepine new users a higher risk (OR = 5.02, p < 0.001).
      Despite the simple measures of cognitive functioning and psychopathology, and the
      approximation in pattern of psychotropic drug use, these results emphasize the
      importance of considering psychotropic drugs in studies of cognitive decline in
      elderly subjects.

PMID- 9193970
TI  - NHS and Community Care Act 1990 and discharge of psychogeriatric inpatients.

PMID- 9193969
TI  - ICD-10 mild cognitive disorder: its outcome three years later.
AB  - OBJECTIVE: The aims were to (i) report the outcome of mild cognitive disorder
      (MCD) 3.6 years after initial interview and diagnosis; (ii) identify predictors
      of new cases of MCD. The hypotheses were that (i) persons with MCD are more
      likely to develop dementia than those without MCD; (ii) symptoms of anxiety or
      depression predict MCD caseness at follow-up. DESIGN: Longitudinal cohort study.
      SETTING: Community of elderly people (age 70-97 years). PARTICIPANTS: 612 of 897
      elderly subjects (mean 76 years) were reinterviewed. Of the 36 MCD cases
      originally identified, 25 were available at follow-up. 24 incident cases of MCD
      were identified. MAIN OUTCOME MEASURES: ICD-10 dementia, DSM-III-R dementia, ICD
      10 mild cognitive disorder diagnoses made by the Canberra Interview for the
      Elderly, tests of anxiety, depression, neuroticism and cognitive performance.
      MAIN RESULTS: Of the original 25 MCD cases available at follow-up, two had a
      diagnosis of MCD, and three had a diagnosis of both ICD-10 and DSM-III-R
      dementia. The prevalence of MCD and DSM-III-R dementia at follow-up was no
      greater for MCD cases diagnosed at initial interview than in normal subjects at
      initial interview. There was, however, an increased prevalence of ICD-10 dementia
      among original MCD cases. At initial interview and at follow-up MCD cases were
      more anxious and depressed but had similar cognitive performance to normals. For
      incident cases of MCD the only significant predictor was age. CONCLUSIONS: MCD
      cannot be seen to be a specific forerunner of dementia. Those with a diagnosis of
      MCD are distinguished more by their anxiety, depression and neuroticism than by
      their cognitive deficits.

PMID- 9193971
TI  - Apolipoprotein E and the cost of Alzheimer's disease.

PMID- 9193973
TI  - Isotope brain scanning with Tc-HMPAO: a predictor of outcome in carbon monoxide
      poisoning?
AB  - Tc-HMPAO isotope brain scans were performed in three patients who received
      hyperbaric oxygen treatment following carbon monoxide poisoning. Cerebral
      perfusion imaging provides an index of severity of the initial cerebral damage
      which correlated with outcome.

PMID- 9193972
TI  - Evaluation of a paired creatine kinase test for the diagnosis of acute myocardial
      infarction in patients with a non-diagnostic electrocardiogram.
AB  - OBJECTIVE: The rate of rise of total plasma creatine kinase (CK) activity in the
      first 12 hours from presentation can be used to diagnose acute myocardial
      infarction. The aim of this study was to evaluate the performance of an
      abbreviated form of this test in the diagnosis of acute myocardial infarction in
      patients in whom the initial electrocardiogram was inconclusive. METHODS: Using a
      protocol that requires only two CK measurements (separated by four hours) to
      estimate the rate of rise, the performance of the test was investigated using
      data accrued from 345 consecutive admissions with suspected acute myocardial
      infarction. RESULTS: A CK increment (delta CK) of > 20% in the first four hours
      from presentation had a diagnostic sensitivity of 84.4% (95% confidence interval
      75.5 to 93.3), specificity of 85.8% (80.1 to 91.5), positive predictive accuracy
      of 73.0% (62.9 to 83.1), and negative predictive accuracy of 92.4% (87.9 to
      96.9). Using more stringent diagnostic criteria (delta CK > 20% and 4 h CK value
      > 160 U/litre) resulted in an increase in specificity and positive predictive
      accuracy to 96.5% and 91.1% respectively, and a small reduction in sensitivity
      and negative predictive accuracy to 79.7% and 91.3%, respectively, 94% of all
      infarcts were correctly identified using the ECG as the initial investigation and
      paired CK measurement as an additional test when this was inconclusive. In the 44
      patients who received thrombolysis on the basis of an early biochemical diagnosis
      of acute myocardial infarction, the median time delay (75th centile) to
      thrombolysis was 10.75 (SD 15.0) hours. CONCLUSIONS: When the presenting ECG is
      non-diagnostic, sequential sampling of cardiac enzymes is a feasible alternative
      in the early diagnosis of patients with suspected myocardial infarction, even in
      the emergency setting. Further studies are required to define the optimal
      biochemical assay and timed sampling protocol.

PMID- 9193976
TI  - Benefits of an accident and emergency short stay ward in the staged hospital care
      of elderly patients.
AB  - OBJECTIVE: To study the potential of a short stay ward attached to an accident
      and emergency (A&E) department to improve care and reduce admissions to hospital
      by enabling elderly patients to be monitored closely for up to 24 h before being
      formally admitted to hospital or discharged home. Patients admitted to the short
      stay ward were those who appeared to need only a brief period of assessment or
      treatment. METHODS: The medical records of all patients aged 65 years and above
      admitted to the short stay ward over a nine month period (April to December 1993,
      inclusive) were reviewed. RESULTS: 13% of all the patients over 65 attending A&E
      were admitted to the A&E ward. Of patients over 65 who were admitted to hospital,
      20% were first admitted to the A&E ward. There were 502 admissions to the short
      stay ward of patients aged 65 years and above, who constituted 38% of the total
      admissions to that ward. Admitting these selected patients to the short stay ward
      allowed 71% to be discharged home, usually within 24 h, rather than being
      formally admitted to hospital. CONCLUSIONS: The addition of a short stay ward can
      shorten the hospital stay for selected elderly patients and reduce the demand for
      inpatient hospital beds. This ward also improves the quality of care to elderly
      patients attending the A&E department.

PMID- 9193974
TI  - Effectiveness of ambulance paramedics versus ambulance technicians in managing
      out of hospital cardiac arrest.
AB  - OBJECTIVE: To determine the effectiveness of extended trained ambulance personnel
      (paramedics) for the management of out of hospital cardiac arrest. METHODS: A
      retrospective cohort study of patients who suffered a cardiac arrest between 1
      January 1992 and 31 July 1994, and who were transported to their local accident
      and emergency (A&E) department. Data were collected on basic demography,
      operational time intervals, and ambulance crew status. Further clinical data were
      collected, and outcome measures included status on arrival at A&E, status on
      leaving A&E (hospital admission), and status on leaving hospital. The data were
      analysed using univariate and multivariate techniques. RESULTS: Univariate
      analysis showed the likelihood of arriving in A&E with a return of spontaneous
      circulation was more than doubled among patients attended by a paramedic crew
      compared with those attended by technicians (relative risk = 2.48, 95% confidence
      interval 1.34 to 4.60). The likelihood of successful hospital admission was also
      significantly increased (RR = 1.92, 95% CI 1.13 to 3.27); however, beyond this
      point, further survival benefits appeared to be much smaller. Similar findings
      were revealed using multivariate analysis. Second level modelling revealed
      further possible differences between paramedic and technician crews according to
      type of incident. Patients successfully admitted to hospital who died before
      discharge remained severely disabled between admission and death. CONCLUSIONS:
      There are marked short term survival advantages after cardiac arrest associated
      with paramedic care, but these probably diminish rapidly over time.

PMID- 9193975
TI  - Paramedic interventions increase the rate of return of spontaneous circulation in
      out of hospital cardiac arrests.
AB  - OBJECTIVE: To determine whether paramedic interventions increased the rate of
      return of spontaneous circulation in the victims of out of hospital cardiac
      arrest. METHODS: A retrospective analysis of 276 out of hospital cardiac arrests
      was made. Data analysed included age, sex, presenting rhythm, ambulance response
      time, presence of a pulse at any point, interventions performed by the ambulance
      crews, and survival to discharge. RESULTS: 146 patients were treated by
      paramedics and 130 by technicians. There was no difference in the rate of return
      of spontaneous circulation or survival to discharge in patients presenting in
      ventricular fibrillation (VF). In non-VF arrests there was no increase in
      survival to discharge, but 15% of patients in non-VF arrests achieved a return of
      spontaneous circulation when treated by paramedics compared to none treated by
      technicians. There were no other significant differences in any of the variables
      assessed. CONCLUSIONS: Out of hospital cardiac arrests presenting in VF are
      managed equally well by paramedics and technicians. However, in non-VF arrests
      there is a significantly increased rate of return of spontaneous circulation in
      those patients attended by paramedics.

PMID- 9193978
TI  - Traumatic intrapericardial diaphragmatic hernia.

PMID- 9193977
TI  - Effect of Strathclyde police initiative "Operation Blade" on accident and
      emergency attendances due to assault.
AB  - OBJECTIVE: To review assault victim attendance at the accident and emergency
      department of Glasgow Royal Infirmary before and after a police initiative to
      curb knife carrying and tackle violent assaults ("Operation Blade"). METHODS:
      Assault victim attendance was reviewed for the month before the implementation of
      Operation Blade and for one month a year later. The number of victims requiring
      treatment in the resuscitation room for stab wounds before, during, and after
      Operation Blade was also reviewed as a crude indicator of the frequency of
      serious assaults in the city. RESULTS: There were no significant differences in
      the nature or number of assault victims attending this hospital one year after
      Operation Blade compared with the month before its implementation. Operation
      Blade reduced the number of serious stabbings for a period of 10 months, but
      subsequently numbers surpassed those prevailing before its implementation.
      CONCLUSIONS: Any attempt to combat this complex and multifactorial problem must
      be addressed through a combined public health and education initiative in
      conjunction with regular press and police campaigns to achieve a sustained
      effect.

PMID- 9193979
TI  - Management of eye emergencies in the accident and emergency department by senior
      house officers: a national survey.
AB  - OBJECTIVE: To assess the training that accident and emergency (A&E) senior house
      officers (SHOs) receive in dealing with eye emergencies, their own perceived
      level of confidence and competence in managing such cases, and the availability
      of appropriate equipment in their departments. METHODS: Prospective telephone
      survey using a standardised structured questionnaire. One SHO from each United
      Kingdom A&E department listed in the BAEM directory of 1993 was chosen at random
      and interviewed. RESULTS: 226 A&E departments were contacted and 192 SHOs were
      successfully interviewed (response rate 84.9%); 26.0% received no training in the
      management of eye emergencies, 68.8% had only a little or no confidence in
      dealing with these cases, and 42.2% worked in A&E departments which had no slit
      lamp. CONCLUSIONS: There is a lack of adequate basic ophthalmic training for A&E
      SHOs, leading to a lack of confidence on their part in the management of eye
      emergencies. In just over 40% of A&E departments in the United Kingdom, the
      management of these cases may be less than optimal because of the absence of a
      slit lamp.

PMID- 9193980
TI  - Do patients get the best deal when antibiotics are prescribed out of hours?
AB  - OBJECTIVE: To investigate patients' compliance in obtaining follow on
      prescriptions after being prescribed a "starter pack" by the accident and
      emergency (A&E) department, and to assess the cost of the starter pack system.
      METHODS: During a study period of two months, out of hours prescriptions of
      antibiotic starter packs in A&E were monitored prospectively to determine how
      many patients returned to the hospital pharmacy or to their general practitioner
      (GP) for the remainder of the prescribed course. Current costs of out of hours
      antibiotic prescriptions were calculated, as were the costs of providing a full
      course of antibiotics on the patient's first visit to the A&E department.
      RESULTS: During the study period, 571 antibiotic items were prescribed as starter
      packs (three days' supply) to 437 patients. Of these, 232 (53%) chose to return
      to the hospital and 175 (40%) to their GP for the follow on prescription to
      complete their course. In 29 cases (7%) the information was not recorded and
      those patients were excluded from analysis. Only 50% of patients electing to
      obtain the follow on prescription from their GP did so compared with 83.7% of
      those electing to return to the hospital pharmacy. Failure to obtain the follow
      on prescription was termed "late primary non-compliance". There was an estimated
      annual saving to the hospital of Pounds 3131 if the patients were given the full
      course of antibiotics at their primary attendance at A&E. CONCLUSIONS: Patients
      prescribed antibiotics out of hours should be dispensed full courses. This would
      eliminate late primary non-compliance at no extra cost to the health authority.

PMID- 9193982
TI  - Tap water as a wound cleansing agent in accident and emergency.
AB  - OBJECTIVE: To investigate the bacterial cleanliness of tap water in a large
      accident and emergency (A&E) department for its possible use in the cleansing and
      irrigation of open traumatic wounds. METHODS: Tap water samples were collected
      from different areas within the department and analysed on two separate occasions
      for coliforms, S aureus, clostridia, pseudomonas, and beta haemolytic
      streptococci. RESULTS: Pathogenic bacteria were not isolated from the tap water
      samples within the A&E department. CONCLUSIONS: Tap water of drinking quality can
      be used to irrigate open traumatic wounds.

PMID- 9193981
TI  - The ability of A&E personnel to demonstrate inhaler technique.
AB  - OBJECTIVE: To determine the ability of accident and emergency (A&E) personnel to
      demonstrate metered dose inhaler technique. METHODS: 25 senior house officers and
      25 nurses working in A&E were individually interviewed and assessed on their
      knowledge of inhaler technique and competence in demonstrating the correct use of
      a metered dose inhaler. RESULTS: Demonstration of inhaler technique was generally
      poor by the staff assessed. Although 22 (88%) of the senior house officers were
      aware of the British Thoracic Society guidelines, only 10 (40%) routinely checked
      inhaler technique when discharging asthmatic patients. CONCLUSIONS: The A&E
      department offers an important opportunity for patient assessment and
      reinforcement of metered dose inhaler technique. Staff should be made aware of
      the British Thoracic Society guidelines and be competent at assessing and
      teaching inhaler technique.

PMID- 9193983
TI  - Whither the acute medical patient?
AB  - The continual change in NHS structure demands reappraisal of both the services
      provided and the allocation of resources to ensure appropriate standards of care.
      Unfortunately this equation never seems to balance. Although the overall goal is
      to have an excellent standard of care, the necessary resources nearly always are
      lacking. As a consequence "we" often have to critically analyse and change
      clinical practice to achieve this goal. Nowhere in medicine is this point more
      pertinent than in the management of acute medical emergencies. This article
      examines not only how the changing face of medicine influences this situation but
      also possible solutions to the question who will manage these patients in the
      future.

PMID- 9193984
TI  - Cardiopulmonary resuscitation following profound immersion hypothermia.
AB  - A case is presented in which prolonged resuscitation and rewarming was performed
      following post-rescue cardiopulmonary arrest in severe immersion hypothermia. The
      rescue and resuscitation techniques necessary to optimise outcome in such cases
      are described.

PMID- 9193986
TI  - Pharyngeal coin removal in children.
AB  - Two cases of coin extraction from the upper third of the oesophagus are
      described, using a Foley catheter in the accident and emergency department
      without complication. Although previously reported, the method is not widely
      used; indeed many junior doctors appear unaware of it. Coins can be removed from
      this proximal position provided the operator is confident and swift. This appears
      to be a safe and useful technique, avoiding the need for hospital admission and
      anaesthesia. It is worth trying before resorting to endoscopy.

PMID- 9193985
TI  - Sixth cranial nerve palsy following closed head injury in a child.
AB  - A five year old female had an isolated abducens nerve palsy following closed head
      injury. There was no associated skull fracture, haematoma, or other cranial nerve
      injury. The significance, frequency, and differential diagnosis of traumatic
      sixth cranial nerve injury is discussed, particularly in paediatric patients.
      Management is symptomatic; occlusion with an eye pad may be used if diplopia is
      significant. In young children alternate day occlusion of each eye will help
      prevent amblyopia. Most cases improve within three months and many resolve by six
      months. Residual palsy at six months is likely to be permanent and surgical
      treatment may be needed.

PMID- 9193987
TI  - Use of ultrasound to aid management of late presentation of Dermatobia hominis
      larva infestation.
AB  - Tropical myiasis is likely to present in the larger second instar larval stage in
      the United Kingdom. The use of ultrasound to confirm the size and determine
      method of removal is described.

PMID- 9193988
TI  - Tropical myiasis: an unwanted holiday souvenir.
AB  - A case of tropical myiasis is described and its treatment outlined.

PMID- 9193989
TI  - Dermatobia hominis in the accident and emergency department: "I've got you under
      my skin".
AB  - An unusual form of larval infestation from South America is presented which, in
      view of increasing tourism to South america's tropical areas, may present to any
      accident and emergency department. Infestation with Dermatobia hominis is
      reviewed in terms of clinical recognition and life cycle. Techniques of removal
      are described.

PMID- 9193990
TI  - A case of muscle abscess presenting to an accident and emergency department.
AB  - A case is reported of a patient with acute primary muscle abscess who presented
      to the accident and emergency department with hip pain. Pyomyositis must be
      considered as a cause of muscle pain especially around the hip. A brief
      discussion of the diagnosis and management of pyomyositis is also presented.

PMID- 9193991
TI  - Malignant hypertension presenting as blurred vision in a 43 year old intravenous
      drug abuser.
AB  - A 43 year old intravenous drug abuser presented to the accident and emergency
      department with a three week history of bilateral visual loss and frontal
      headaches. Fundoscopy revealed bilateral retinal cotton wool spots and
      haemorrhages and an ophthalmic opinion was requested. His blood pressure was
      subsequently found to be 210/140. A diagnosis of malignant hypertension was made
      and blood pressure was gradually controlled on oral antihypertensives. This case
      illustrates the importance of checking the blood pressure of all patients
      presenting with visual loss.

PMID- 9193992
TI  - Accidental ingestion of Ecstasy by a toddler: unusual cause for convulsion in a
      febrile child.
AB  - The case is reported of a toddler who presented with an apparent febrile
      convulsion. The final diagnosis was that of accidental ingestion of Ecstasy. The
      child made an uneventful recovery. Ecstasy toxicity should be added to the list
      of differential diagnoses in a child presenting with fever and an unexplained
      seizure.

PMID- 9193993
TI  - Occult gunshot injury of the temporal bone.
AB  - Increasing firearms violence has produced much public disquiet in recent months
      and Liverpool has seen a particularly well publicized spate of shootings. This is
      a case report of an initially occult intracranial injury which illustrates the
      unpredictable nature of missile trauma and the importance of computerised
      tomography in all cases of gunshot injury to the head.

PMID- 9193994
TI  - Budget management.
AB  - Budgetary responsibility gives you more control. Take time to master the fine
      detail, ask questions of your management and finance colleagues about anything
      you do not understand (you will not lose face), and develop the skills of lateral
      thinking and creative accountancy. Even if your budget is repeatedly overspent do
      not take it personally, ensure that management are aware of it and have a good
      night's sleep. Do not worry about it.

PMID- 9193995
TI  - Cyanoacrylate adhesive mistaken for ear drops.

PMID- 9193996
TI  - Local infections at cannula site.

PMID- 9193997
TI  - How safe are schools?

PMID- 9193998
TI  - British poison centres' advice concerning dothiepin overdosage in young children.

PMID- 9193999
TI  - Homeless people and A&E.

PMID- 9194000
TI  - Troponin T in patients with cardiac chest pain.

PMID- 9194001
TI  - Management of major trauma.

PMID- 9194002
TI  - Treatment of focal status epilepticus with lignocaine.

PMID- 9194003
TI  - Decision support for telephone advice.

PMID- 9194004
TI  - Training issues in cognitive-behavioral psychotherapy.
AB  - Because of changes in the health-care system that tend to emphasize short-term
      treatment, the number of graduate students and psychotherapists interested in
      learning cognitive-behavioral techniques is increasing. The present study
      examines how pre-existing biases toward cognitive-behavioral therapy may affect
      acquisition of knowledge, attitude change, and use of cognitive-behavioral
      techniques over a nine-month practicum. Forty graduate students were classified
      by their theoretical orientation: cognitive-behavioral, not cognitive-behavioral,
      and undecided. Results indicated that all students gained significant amounts of
      knowledge, had greater positive attitudes about cognitive-behavioral therapy, and
      used more cognitive and behavioral techniques at the end of the practicum than at
      the beginning. These findings suggest that pre-existing theoretical orientations
      may not significantly affect learning of cognitive-behavioral techniques.

PMID- 9194006
TI  - A cognitive behavioural approach to preventing anxiety during magnetic resonance
      imaging.
AB  - This study evaluated a relaxation intervention designed to prevent anxiety during
      magnetic resonance imaging (MRI), and assessed the development of fears in
      patients who felt anxious during the procedure. Patients were assigned to a
      control condition (no intervention; n = 52), relaxation before the scan (n = 44),
      or relaxation before and during the scan (n = 43). Compared to the control group,
      patients who practised relaxation showed reduced anxiety during the scan. Seven
      months or more after undergoing MRI, there was a positive correlation between
      anxiety experienced during the scan and the development of MRI-related fears. The
      intervention did not prevent the development of MRI-related fears at follow-up.

PMID- 9194005
TI  - HIV risk reduction for the seriously mentally ill: pilot investigation and call
      for research.
AB  - Research indicates that people with serious mental illnesses (SMI; e.g.,
      schizophrenia, schizoaffective disorder, bipolar disorder) are at enhanced risk
      for infection with the human immunodeficiency virus (HIV). To decrease this risk,
      we piloted a six-session HIV-risk reduction intervention for two single-gender
      groups (nine women, eight men; M age = 39.8 years) of SMI outpatients. The
      intervention and assessment were based on the Information-Motivation-Behavioral
      Skills model of HIV-preventive behavior (Fisher & Fisher, 1992, Psychological
      Bulletin, 111, 455-474) and employed activities designed specifically for people
      with a SMI. Data were collected at pre- and post-interventions and at a one-month
      follow-up. Results indicated that this brief intervention resulted in enhanced
      HIV-related knowledge, and trends toward enhanced skill at condom use negotiation
      and condom use self-efficacy. Overall, a modest decrease in risk behavior among
      participants was observed. Thus, this pilot investigation revealed that HIV
      related risk of the SMI can be reduced through traditional behavioral skills and
      education methods. Future research employing control groups, more intensive
      interventions, and baseline screening for high risk is encouraged.

PMID- 9194007
TI  - Long-term maintenance of a behavioral alternative to surgery for severe vomiting
      and weight loss.
AB  - A 34-year-old woman with severe mental retardation suffered from gastroesophageal
      reflux, projectile vomiting, weight loss, and a prepyloric ulcer. Despite the
      implementation of non-intrusive behavior treatment procedures involving simple
      correction and differential reinforcement (Treatment A), fundoplication surgery
      with implantation of a gastrostomy feeding tube had been recommended. A
      descriptive functional analysis suggested that the woman's vomiting was
      maintained by escape. Revised treatment was implemented throughout her waking
      hours. Treatment B consisted of the addition of escape extinction and antecedent
      control procedures. Treatment C added to these procedures food choice and
      additional differential reinforcement procedures. Results showed the respective
      mean frequency of vomiting and mean weight were: Treatment A--1.4 episodes/day
      and 118 lbs; Treatment B--1.1 episodes/day and 105 lbs; Treatment C--0.2
      incidents/day and 133 lbs. The woman's progress has been maintained for nearly 2
      years.

PMID- 9194008
TI  - An inventory method for assessing the degree of restraint imposed by others.
AB  - An inventory for assessing the degree of mechanical restraint imposed by others
      to prevent individuals from inflicting physical injuries to themselves or to
      others, the Imposed Mechanical Restraint Inventory (IMRI), was developed. The
      inventory was administered to pairs of residential direct-care staff members to
      assess 113 individuals with mental retardation who showed self-injurious behavior
      while various sorts of mechanical restraint were imposed on them. The results
      indicate that the inventory showed acceptable levels of interobserver
      reliability, intraobserver reliability, and accuracy.

PMID- 9194009
TI  - Reducing excessive vocal loudness in persons with mental retardation through the
      use of a portable auditory-feedback device.
AB  - A simple portable device was used to reduce excessive vocal loudness in two
      adults affected by moderate mental retardation. The device provided these adults
      with auditory feedback (a pulsating tone of about 300 Hz and 80 dB) when their
      vocal loudness exceeded a preset limit. Data showed that the device was effective
      in helping the two adults reduce their excessive vocal loudness. The use of the
      device continued to produce positive effects over time. Implications of these
      findings are discussed.

PMID- 9194011
TI  - Bibliotherapy in unipolar depression: a meta-analysis.
AB  - In the last decades, several therapies for unipolar depression have been
      developed, for example cognitive therapy, behavior therapy and pharmacotherapy. A
      new kind of therapy is bibliotherapy. What is new in this treatment modality is
      not the content, because bibliotherapy usually uses a cognitive-behavioral
      approach. Only the form in which it is presented is new. In bibliotherapy the
      patient takes a standardized treatment home, in book form, and works it through
      more or less independently. Contacts with therapists are only supportive or
      facilitative. No traditional relationship between therapist and patient is
      developed. In this article the relevance of bibliotherapy for the clinical
      practice is presented and a meta-analysis of the research into bibliotherapy is
      described.

PMID- 9194010
TI  - Behavioral assessment of relaxation: the validity of a Behavioral Rating Scale.
AB  - Poppen (Behavior Relaxation Training and Assessment, 1988) has developed an
      observational method of assessing the degree to which individuals show a
      relaxation response. Although promising, this method, the Behavioral Rating Scale
      (BRS), has yet to be thoroughly investigated. Subjects in this study were
      randomly assigned to a progressive relaxation training group or an attention
      control group. Following a training period, subjects participated in a laboratory
      session in which self-report measures of relaxation were obtained, physiological
      measures were monitored, and behavioral observations were made using the BRS.
      Results supported the use of the BRS as a valid, observable measure of an
      individual's relaxation response. Discriminant validity was demonstrated by
      between-group differences on the BRS and construct validity was shown by
      significant correlations between changes on the BRS and changes on self-report
      and physiological measures. It is argued that, though alternative explanations
      are feasible, this study's results support the use of the BRS as an effective
      assessment tool when measuring an individual's response to progressive muscle
      relaxation.

PMID- 9194012
TI  - Use of the Child Behavior Checklist and DSM-III-R diagnosis in predicting outcome
      of children's social skills training.
AB  - A standardized 12-week cognitive-behavioral social skills package in which
      parents assisted children with socialization homework assignments, was presented
      to 52 nonpsychotic outpatient boys, many of whom were diagnosed with DSM-III-R
      Attention Deficit-Hyperactivity Disorder and Oppositional Defiant Disorder.
      Results demonstrated that the Thought Problems factor of the mother-completed
      Child Behavior Checklist aided in predicting changes in teacher-rated aggression.
      DSM-III-R diagnosis of Oppositional Defiant Disorder predicted changes in teacher
      rated withdrawal subsequent to treatment. The need for research to determine
      which children benefit from which treatment was discussed.

PMID- 9194013
TI  - Teaching toilet skills in a public school setting to a child with pervasive
      developmental disorder.
AB  - An 8-year old boy with Pervasive Developmental Disorder (PDD) was taught
      toileting skills within a public elementary school. During baseline, he never
      urinated successfully in the toilet and wore a disposable diaper throughout the
      day. The training program included scheduling a toileting opportunity at a time
      that increased the likelihood of urination and providing positive reinforcement
      when voiding in the toilet occurred. Toileting skills were established rapidly
      and were maintained when another bathroom visit was added to the toileting
      schedule, primary reinforcement was eliminated, and the boy no longer wore a
      disposable diaper. Issues related to behavioral support programming within
      inclusive educational settings are discussed.

PMID- 9194014
TI  - Hyperventilation syndrome: a chimera?
AB  - There is now an impressive body of research to suggest that the concept of a
      discrete hyperventilation syndrome is no longer tenable. The evidence for this
      has been carefully gathered and the scientific studies have employed innovative
      methodological techniques and have introduced a key psychological dimension. Both
      have led to a greater understanding of the respiratory correlates of anxiety, but
      in the process have revealed the "hyperventilation syndrome" to be a chimera.
      Furthermore, there is no evidence to support the view that panic attacks and
      hyperventilation are synonymous: on the contrary, hyperventilation rarely
      accompanies panic and, when it does, it is more likely to be a consequence than a
      cause of the panic. Finally, there is no evidence that "breathing therapy" works
      by normalizing pCO2; its nonspecific effects on anxiety appear to be mediated in
      part by slowing respiratory rate. Further research in this field might be more
      profitably focused on the nature of the association between anxiety disorders and
      organic lung disease, especially asthma.

PMID- 9194015
TI  - Hypersensitivity to electricity: sense or sensibility?

PMID- 9194016
TI  - Psychological aspects of chronic pelvic pain.
AB  - Chronic pelvic pain (CPP) is a common gynecological problem which is poorly
      understood. A physical cause for the pain often cannot be established and,
      consequently, it has been difficult to treat successfully. In the absence of an
      identifiable physical cause for pain, researchers have attempted to identify a
      psychopathological causation. Associations have been reported between CPP and
      factors including personality and mood disturbance, childhood events,
      particularly sexual abuse, and sexual and relationship difficulties. However,
      evidence that women with CPP without discernible pathology differ in personality,
      psychological state, or life experiences from women with an identifiable cause
      for the pain, or those without chronic pelvic pain, is inconclusive. This review
      highlights methodological flaws inherent in many of the studies. It suggests
      areas and approaches for future research adopting a broader biopsychosocial
      perspective, which may generate findings of greater clinical utility.

PMID- 9194017
TI  - Psychiatric complications of hemodialysis at a kidney center in Nigeria.
AB  - The mental state of 20 consecutive hemodialysis patients investigated at a
      Nigerian renal unit was assessed using the 30-item General Health Questionnaire,
      Present State Examination, and clinical evaluation using the Diagnostic and
      Statistical Manual, revised third edition (DSM-III-R). Findings were compared
      with those of orthopedic patients and apparently healthy controls. A standard
      interview was used in eliciting sociodemographic data from the subjects. A
      significantly higher prevalence of psychiatric disorders was identified in
      hemodialysis patients (55%) than in orthopedic patients (20%) and apparently
      healthy controls (0%). The psychiatric disorders encountered in this hemodialysis
      population included major depressive episode (35%) and generalized anxiety
      disorder (20%). The probable reasons for the higher prevalence of psychiatric
      morbidity in this hemodialysis population, compared with those in Western
      societies, are discussed. Psychiatric morbidity was higher in patients with low
      levels of education, and did not show statistically significant relationship with
      other sociodemographic variables.

PMID- 9194018
TI  - Effectiveness of a short-term group psychotherapy program on endocrine and immune
      function in breast cancer patients: an exploratory study.
AB  - Cancer patients who had been treated for early stage breast cancer and were
      diagnosed with either positive axillary lymph nodes or distant metastases were
      randomly assigned to either a 13-week experiential-existential group
      psychotherapy (EEGP) program or a waiting list control (WLC) condition. Endocrine
      and immune measures were obtained before and after the intervention period. The
      findings of this study are that, after the 13 weeks of the experiment, patients
      in the EEGP group showed lower levels of plasma cortisol and lower levels of
      prolactin as well as lower percentages of natural killer cells, CD8 cells, and
      CD4 cells in addition to a lower proliferative response to pokeweed mitogen than
      patients in the WLC group. Importantly, this was only found in those breast
      cancer patients presenting relatively high endocrine and immune baseline levels,
      suggesting that the patients' profile with regard to endocrine and immune
      function at the start of a program can have an important effect. If replicated on
      a larger scale, the current results may be relevant for the treatment of breast
      cancer.

PMID- 9194019
TI  - Assessing illness-related stress in psoriasis: the psychometric properties of the
      Psoriasis Life Stress Inventory.
AB  - The purpose of the present study was to undertake a clinical and psychometric
      reappraisal of the Psoriasis Life Stress Inventory (PLSI). Total PLSI score was
      inversely related to age of onset of psoriasis, but bore no significant
      relationship to duration or to clinical severity. Similarly, patients' stress
      score did not differ with regards to the nature of their current treatment, to
      their beliefs as to what was responsible for exacerbation or improvement of their
      condition, or to the patients' gender. Factor analysis extracted two factors
      which suggested that the psychosocial impact of psoriasis results from stress
      associated with: (i) engaging in anticipatory/avoidance coping behavior that is
      effected to limit the sociocognitive intrusiveness of psoriasis; and (ii) stress
      resulting from patients' beliefs or actual experiences of being evaluated by
      others solely on the basis of their skin. The internal reliability of the scale
      can be improved by the deletion of three items. Revision of the PLSI is
      recommended to render it psychometrically and clinically acceptable for use in
      the UK.

PMID- 9194020
TI  - Delusional pregnancy with polydipsia: a case report.
AB  - We report a case of delusional pregnancy with polydipsia in a female patient with
      paranoid schizophrenia. The contribution of psychological and physiological
      factors in the development of the delusion of pregnancy and polydipsia and the
      possible interactions between the two phenomena are discussed.

PMID- 9194021
TI  - Teaching psychosomatic medicine: predictors of students' attitudes toward a
      compulsory course.
AB  - One hundred five medical students (59 males, 46 females, mean age 25.7 +/- 2.5
      years) were asked to evaluate a one-semester course in psychosomatic medicine.
      Overall satisfaction with the course was good. Neither demographic data nor
      individual characteristics such as previous personal experience in psychosocial
      medicine, professional goals, or preferred theoretical model of medicine were
      significantly correlated with single evaluation criteria or overall satisfaction
      with the course. The latter was most significantly related to the teachers'
      performance (r = 0.80).

PMID- 9194022
TI  - BSE, public anxiety and private neurosis.
AB  - Following the recent focus of media attention on BSE, and the putative link
      between the cattle disease and cases of variant CJD in humans in the UK, we
      report two cases of "BSE phobia." The relationship between popular conceptions of
      science and psychopathology is discussed.

PMID- 9194023
TI  - Treatment of HIV-related psychotic disorders with risperidone: a series of 21
      cases.
AB  - We describe a consecutive series of 21 patients with HIV or AIDS who received
      risperidone for psychotic disorders. Of these, 13 became symptom-free, 7 showed
      substantial improvement, and 1 had no response. Most responded to low doses of
      risperidone (mean maximum dose 3.3 mg) and needed only a short course of
      treatment (mean 6.4 weeks). The 12 manic patients did particularly well: 9 became
      symptom-free and the mean Young mania rating scale fell from 28.36 to 3.91. No
      serious adverse effects were reported. Three patients became drowsy and two
      experienced drooling, but these resolved after dose reductions or at the end of
      treatment. No adverse hematological effects were observed. We suggest that
      risperidone may be the treatment of choice for patients with HIV-related
      psychotic disorders.

PMID- 9194024
TI  - Pseudoseizure "status".
AB  - Psychogenic pain, disturbances of gait and stance, sensory symptoms, dizziness,
      and psychogenic seizures have been found to be the most common conversion
      symptoms in neurology clinics. A retrospective analysis of 18 patients suffering
      from pseudoseizure "status" is presented in this study. All of the patients
      fulfilled the DSM-III-R criteria of conversion disorder. However, 5 of them had
      concomitant major depression, 6 suffered from bulimia nervosa, and 7 met the
      criteria for substance abuse. On Axis II, 10 cases of borderline personality
      disorder, 2 cases of antisocial personality disorder, and 3 cases of histrionic
      personality disorder were diagnosed. The majority of the patients had attempted
      suicide and other forms of self-destructive behavior. The findings suggest that
      patients with pseudoseizure "status" suffer from severe affective imbalances and
      disturbed impulse control.

PMID- 9194025
TI  - How not to miss a somatic needle in the haystack of chronic pain.
AB  - Interviews with 18 male patients with predominantly psychogenic pain (DSM-III and
      DSM-III-R) and with 18 male patients with pain of mainly physical origin,
      consecutively admitted to a medical department, were rated by blinded and
      independent raters with respect to "symptom description," "manner of speech,"
      "personality characteristics," "interviewer reactions," "interpersonal
      relationships," and "relationships at work." Patients with predominantly organic
      pain significantly more often described a clear localization of the pain symptom,
      used more sensory words for the description of pain quality; more often described
      discrete changes of pain intensity and periodicity; more often showed pain
      intensifying factors dependent on movement and pain-decreasing factors; more
      often believed pain to be a symptom versus as a disease itself, and tended to
      have fewer difficulties in their interpersonal relationships than those with
      predominantly psychogenic pain (p < 0.05 for all factors, two-tailed Fisher's
      Exact test).

PMID- 9194026
TI  - Cancer, cigarette smoking and premature death in Europe: a review including the
      Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October
      1996.
AB  - Cigarette smoking has been clearly and unambiguously identified as a direct cause
      of cancers of the oral cavity, oesophagus, stomach, pancreas, larynx, lung,
      bladder, kidney and leukaemia, especially acute myeloid leukaemia. Additionally,
      cigarette smoking is a direct cause of ischaemic heart disease (the commonest
      cause of death in western countries), respiratory heart disease, aortic aneurysm,
      chronic obstructive lung disease, stroke, pneumonia and cirrhosis and cancer of
      the liver. Cigarette smoking can kill in 24 different ways and, although smoking
      protects against several fatal and non-fatal conditions, the adverse effect of
      smoking on health is largely negative. In developed countries as a whole, tobacco
      is responsible for 24% of all male deaths and 7% of all female deaths: these
      figures rise to over 40% in men in some countries of central and eastern Europe
      and to 17% in women in the United States. The average loss of life of smokers is
      8 years. Among United Kingdom doctors followed for 40 years, overall death rates
      in middle age were about three times higher among doctors who smoked cigarettes
      as among doctors who had never smoked regularly. About half of all regular
      cigarette smokers will eventually be killed by their habit. The important
      information is that it is never too late to stop smoking: among United Kingdom
      doctors who stopped smoking, even in middle age, there was a substantial
      improvement in life expectancy. World-wide, smoking is killing three million
      people each year and this figure is increasing. In most countries the worst is
      yet to come, since by the time the young smokers of today reach middle or old age
      there will be about 10 million deaths/year from tobacco. Approximately 500
      million individuals alive today can expect to be killed by tobacco, 250 million
      of these deaths will occur in middle age. Tobacco is already the biggest cause of
      adult death in developed countries. Over the next few decades tobacco could well
      become the biggest cause of adult death in the world. For men in developed
      countries, the full effects of smoking can already be seen. Tobacco now causes
      one-third of all male deaths in middle age (plus one fifth in old age). Tobacco
      is a cause of about half of all male cancer deaths in middle age (plus one-third
      in old age). Of those who start smoking in their teenage years and keep on
      smoking, about half will be killed by tobacco. Half of these deaths will be in
      middle age (35-69) and each will lose an average of 20-25 years of non-smoker
      life expectancy. In non-smokers in many countries, cancer mortality is decreasing
      slowly and total mortality rapidly. The war against cancer is being won slowly:
      the effects of cigarette smoking are holding back this victory. Lung cancer now
      kills more women in the United States each year than breast cancer. For women in
      developed countries, the peak of the tobacco epidemic has not yet arrived.
      Tobacco now causes almost one-third of all deaths in women in middle age in the
      United States. Although it has only 5% of the world's female population, the
      United States has 50% of the world's deaths from smoking in women. Tobacco
      smoking is a major cause of premature death. Throughout Europe, in 1990 tobacco
      smoking caused three quarters of a million deaths in middle age (between 35 and
      69). In the Member States of the European Union in 1990 there were over one
      quarter of a million deaths in middle age directly caused by tobacco smoking:
      there were 219700 in men and 31900 in women. There were many more deaths caused
      by tobacco at older ages. In countries of central and eastern Europe, including
      the former USSR, there were 441200 deaths in middle age in men and 42100 deaths
      in women. There is a need for urgent action to help contain this important and
      unnecessary loss of life. In formulating Recommendations, the European Cancer
      Experts Consensus Committee recognised that Tobacco Control depends on various
      parts of society and not only on the individual.

PMID- 9194027
TI  - Frequency of the variant allele CYP2D6(C) among North American Caucasian lung
      cancer patients and controls.
AB  - Previous reports of the association between the debrisoquine polymorphism and
      lung cancer risk are conflicting. Following the report of an association between
      lung cancer risk and the variant allele CYP2D6(C), we examined the presence of
      this allele in 98 incident Caucasian lung cancer patients and 110 age, race, and
      sex matched hospital controls from a case-control study conducted at the National
      Naval Medical Center in Bethesda, MD. Debrisoquine metabolic phenotype was
      determined by debrisoquine administration and analysis of debrisoquine and 4
      hydroxydebrisoquine in the subsequent 8 h urine collected. Genomic DNA was
      genotyped by a specific polymerase chain reaction amplification and subsequent
      restriction enzyme digestion, and Southern analysis. Twenty subjects were
      heterozygous for the CYP2D6(C) allele but none were homozygous for this allele.
      There was no significant difference in frequency of CYP2D6(C) between lung cancer
      patients and controls (5.61% and 4.09%, respectively), and there was no
      significant heterogeneity among cases by histologic type of lung cancer (P =
      0.08). However, 7 of 11 cases (64%) with the CYP2D6(C) allele had small cell lung
      cancer, and none had squamous cell carcinoma. Carrying the CYP2D6(C) allele did
      not impair debrisoquine metabolism to the same degree as the known inactivating
      mutations, CYP2D6(A) and CYP2D6(B), or deletion of CYP2D6. Thus, the CYP2D6(C)
      allele does not encode a completely inactivating mutation, and the suggestion of
      a role for this variant allele in the risk for specific histologic types of lung
      cancer justifies further investigation.

PMID- 9194029
TI  - In vitro confirmation of newly established lung cancer cell lines using flow
      cytometry and multicellular tumor spheroids.
AB  - We report on a simplified method of cytomorphological in vitro confirmation of
      newly established lung cancer cell lines by using multicellular tumor spheroids
      (MTS) and flow cytometry (FCM). Eleven cell lines were established from 11
      patients with lung cancer. The MTS were produced by culturing cells in agar
      coated dish. Cytomorphological studies were made using smears of crushed MTS and
      frozen sections of MTS. The MTS were fixed doubly with paraformaldehyde and osmic
      acid for scanning and transmission electron microscopy. Bivariate fluorescence of
      fluorescein isothyocyanate (FITC, tumor associated antigen, TAA) and propidium
      iodide (DNA) were measured by FCM. The MTS grew anchorage-independently.
      Cytopathological and electron microscopic findings of MTS were similar to those
      of the original clinical specimens. The DNA index and TAA were useful in
      evaluating the presence or absence of contamination by cells of non-tumor origin.
      The new cell lines satisfied a minimum of four conditions to confirm their
      establishment: (a) they originated from humans, (b) they were cytomorphologically
      identified with specimens from primary lesions, (c) they showed tumorigenicity,
      and (d) they were free from contamination by cells of different origin. From
      these findings, the establishment of new cell lines can be confirmed in vitro by
      using MTS and FCM.

PMID- 9194028
TI  - Role of tyrosine specific phosphorylation of cellular proteins, especially EGF
      receptor and p125FAK in human lung cancer cells.
AB  - To clarify the role of tyrosine phosphorylation of cellular proteins in human
      lung cancer cells, phosphotyrosine (PTYR)-containing proteins in lung cancer cell
      lines and in paired tissues resected from cancerous and normal lungs were studied
      by immunoblotting with an anti-PTYR antibody. We found that the profiles of
      protein phosphorylation were very similar among those cell lines which had
      different histological features. The major PTYR-containing proteins (180-190 KDa,
      120-130 KD, and 95-100 KDa) were detected in lung cancer cell lines. The
      expression of EGF receptor (EGF-r) (p185) and o-erb B2 protein, and tyrosine
      phosphorylation of p125FAK were examined in cancerous lung tissues and normal
      lung tissues. In surgical specimens, approximately half of the samples of lung
      cancer tissues showed clear elevation of tyrosine phosphorylation. In these
      cancerous tissues, no clear amplification of EGF-r and c-erb B2 protein
      expression was observed. However, elevation of tyrosine phosphorylation of
      p125FAK was observed in cancerous lung tissues but not in normal lung tissues,
      and its phosphorylation was closely correlated with the nodal involvement of
      cancer and disease-free survival time. These results suggested that the
      intracellular signaling pathway via tyrosine phosphorylation plays a role in the
      generation and immortalization of lung cancer, and assessment of tyrosine
      phosphorylation of cellular proteins. especially p125FAK, may be available
      clinically as a prognostic factor.

PMID- 9194030
TI  - Expression of nm23 protein in pulmonary adenocarcinomas: inverse 1orrelation to
      tumor progression.
AB  - Immunohistochemical assessment was made of nm23 protein expression in pulmonary
      adenocarcinoma. Of the 147 adenocarcinomas 67% (99/147) were weakly and 33%
      (48/147) strongly positive for nm23 protein. nm23 protein expression in primary
      tumors was shown to correlate inversely with advancing pathologic stage and the
      degree of metastasis in regional lymph nodes (P < 0.05). The staining of tumors
      without nodal metastasis was more intense than with nodal metastasis (P < 0.02).
      Nodal metastasis was seen in 37% (55/147) cases examined. The immunoreactivity to
      nm23 protein in tumor cells of nodal metastasis was essentially the same as in
      those of primary tumors (P < 0.01). Significant correlation between patient
      prognosis and immunoreactivity for nm23 in primary tumors (P < 0.05) was
      demonstrated. But none could be found between immunoreactivity and other
      parameters such as histologic grading, distant metastasis, tumor size or disease
      free survival. Neither was there any significant correlation between pathologic
      parameters examined and the expression of nm23 in any histologic subtype.
      Multivariate analysis using Cox's proportional hazards regression model with five
      variables indicated nm23 and lymph node metastasis to contribute to overall
      patient survival. Based on risk ratio disadvantageous state/advantageous states,
      the gravity of prognostic factors was assessed for lymph node metastasis as 9.25,
      nm23 expression as 2.06, distant metastasis as 1.23, pathologic stage as 0.78 and
      tumor size as 0.77. The results suggested that in pulmonary adenocarcinoma a
      reduced expression of nm23 protein was associated with lymph node metastasis and
      poor patient survival.

PMID- 9194031
TI  - Validity of the stage of lung cancer in records of the Maastricht cancer
      registry, The Netherlands.
AB  - Information collected in a clinical study on a random sample of 99 patients with
      inoperable lung cancer, treated with radiotherapy, was compared to the staging
      information in the Maastricht cancer registry. Validity of sex (0%
      disagreements), date of birth (0%), histology (1% major disagreements) and
      treatment (1%) was high, but the validity of stage was lower: 12% major and 23%
      minor disagreements. The misclassification of stage did not result in a shift in
      the survival estimates. If cancer registries intend to use stage in comparisons
      of survival, more validation studies are necessary.

PMID- 9194032
TI  - Prognostic value of histology in patients with non-small cell lung cancer.
AB  - To evaluate the impact of non-small cell lung cancer (NSCLC) histological
      subtypes on survival, we performed a retrospective multivariate analysis of
      survival in 361 patients with a NSCLC diagnosed in 1987 and 1988 at the
      University Hospital in Strasbourg, France. There were 262 (73%) squamous cell
      carcinomas (SQ), 59 (16%) adenocarcinomas other than bronchioloalveolar carcinoma
      (ADOBAC), 24 (7%) bronchioloalveolar carcinoma (BAC) and 16 (4%) large cell
      carcinomas (LC). The proportion of metastatic disease was significantly higher in
      the ADOBAC group than in the SQ group (30% vs. 15%, P < 0.001). In operated
      patients, only extent of disease and age were independent prognostic factors. In
      patients with unresectable NSCLC, extent of disease had also the heaviest impact
      on survival. However, in these unresected patients, ADOBAC had a pejorative
      impact on survival, in contrast to BAC which was of better prognosis. If these
      results are confirmed by prospective studies, this will support stratification
      according to histological subtypes in clinical trials involving inoperable NSCLC
      patients.

PMID- 9194033
TI  - A morphologic study of nodular lung carcinomas and their possible pathogenesis
      from a cluster of non-obstructive bronchiectasis.
AB  - A very simple procedure has enabled us to show that nodular lung carcinomas
      correspond, to a high degree, to neoplasias arising in a cluster of
      bronchiectasis of the non-obstructive type. This pathogenesis explains their
      peculiar features: the round shape with a sharp borderline on the surrounding
      lung, the frequent cavitation, the prevailing histologic type of epidermoid
      carcinomas. At present, when thin-section CT allows discovery of bronchiectasis
      with no need for bronchography, this interpretation suggests the possibility of
      carrying out a prevention program which should consist of identifying the high
      risk group of patients with bronchiectasis, 'sputum producers' and smokers, in
      which an early diagnosis of nodular lung carcinoma might be realized by
      periodical diagnostic cytology.

PMID- 9194034
TI  - Neoadjuvant therapy for surgically staged IIIA N2 non-small cell lung cancer
      (NSCLC).
AB  - INTRODUCTION: Neoadjuvant therapy in patients with Stage IIIA NSCLC is associated
      with a 50-70% resection rate and a 3-5 year survival of 20-32%, but few trials
      have required meticulous staging of the mediastinum to ensure homogeneity of the
      study population. Continuous infusion cisplatin 25 mg/m2/day 1-5, 5-fluorouracil
      800 mg/m2/day 2-5, and high-dose leukovorin 500 mg/m2/day 1-5 (PFL) given every 4
      weeks achieved a 41% response rate in metastatic NSCLC (Lynch TJ, Kalish LA, Kass
      F, Strauss G, Elias A, Skarin A, Shulman L, Sugarbaker D, Frei E. Continuous
      infusion cisplatin, 5-fluorouracil, and leukovorin for advanced non-small cell
      lung cancer. Cancer 1994; 73: 1171-1176). The regimen was therefore evaluated in
      34 patients with pathologic Stage IIIA N2 disease between 3/91 and 10/92.
      METHODS: Staging consisted of chest, liver, brain computerized tomography and
      bone scan, bronchoscopy and surgical mediastinal node mapping. Patients received
      PFL for 3 cycles, followed by thoracotomy and thoracic radiotherapy (TRT) to 54
      60 Gy. RESULTS: Median age was 57 (42-68) years. Demographic factors included:
      male 56%; adenocarcinoma 59%, squamous cell carcinoma 24%; Stage T3N2 26%, T2N2
      56%, and T1N2 18%. No treatment related deaths occurred. Radiographically defined
      response to PFL was 65% (6% complete). Thoracotomy was performed in 28 patients
      (82%) (6 had no attempt due to disease progression). Complete resection was
      achieved in 21 (75%) and seven were unresectable. Pathologic complete response
      was observed in five patients (15%) and an additional unresectable patient had
      fibrosis-only documented at thoracotomy for an overall clinicopathologic response
      rate of 76% (18% pathologic CR). Another ten patients had residual primary with
      or without hilar disease with resolution of previously documented mediastinal
      involvement. Six (18%) patients remain alive and disease-free with a median
      follow-up of 46 (33-50) months, four of whom had achieved pathologic complete
      response at time of surgery. CONCLUSIONS: Long-term event-free survival was
      associated with complete surgical resection which in turn was associated with
      clinical response to chemotherapy. There was a possible trend associating
      pathologic downstaging (absent residual disease in mediastinal nodes),
      particularly pathologic complete response observed in patients with non-bulky
      mediastinal disease, with improved event-free survival. Pathologic downstaging
      might therefore be a useful surrogate endpoint in trials evaluating the
      preoperative activity of new chemotherapy regimens. While radiographic response
      generally correlated with findings at surgery, response as determined by
      histologic examination of resected tissue was generally more extensive and may
      more accurately reflect the systemic impact of the chemotherapy regimen.

PMID- 9194035
TI  - Prevention and early detection of lung cancer-clinical aspects.

PMID- 9194036
TI  - An ATP bioluminescence assay applicable to rapid fluconazole susceptibility
      testing of dermatophytes.
AB  - An ATP bioluminescence assay as a rapid reference method for fluconazole (FLCZ)
      susceptibility testing of dermatophytes, as well as yeasts, was developed and
      evaluated by comparing it with viability, turbidity and fungal protein content
      based conventional methods. FLCZ susceptibility results obtained with strains of
      Candida albicans and dermatophytes by the bioluminescence method in high
      resolution medium were well correlated with those obtained by conventional
      methods currently used in clinical microbiology laboratories or reported
      previously, including a broth dilution method by the National Committee for
      Clinical Laboratory Standards (NCCLS). Thus, ATP bioluminescence assay can be
      used to monitor fungal growth in liquid culture media. The procedure has
      considerable potential for the rapid testing of FLCZ susceptibility of
      dermatophytes and other fungi.

PMID- 9194037
TI  - Serological indicators of Helicobacter pylori infection in adult dyspeptic
      patients and healthy blood donors.
AB  - The levels of IgM, IgG and IgA antibodies reacting with two Helicobacter pylori
      antigens (glycine acid extract (GE) and a recombinant CagA protein) were
      determined in the sera from adult dyspeptic patients, positive (H.p.(+)) or
      negative (H.p.(-)) for H. pylori urease/culture, and from healthy blood donors.
      All sera were also examined against GE by Western blot (Immunoblot) technique.
      Similar levels of anti-GE IgG were detected in the sera from all H.p.(+) and
      almost all H.p.(-) patients and from over 40% of the healthy volunteers. In
      contrast, higher levels of anti-GE IgA were found in the sera from patients than
      that from healthy subjects, although such antibodies were not detected in the
      sera from 30% of the H.p.(+) patients. In general, our results suggest that a
      combination of ELISA and immunoblot may be more sensitive in the detection of H.
      pylori infection in dyspeptic patients than the examination of biopsy specimens
      by culturing or histology.

PMID- 9194038
TI  - Ultrastructural alterations of Candida albicans induced by a new imidazole
      antimycotic omoconazole nitrate.
AB  - The antifungal effects of an imidazole-antimycotic omoconazole nitrate (OMZ) on
      the morphology and ultrastructure of Candida albicans yeast cells were studied
      using scanning and transmission electron microscopy. The treatment of growing
      Candida cultures with fungistatic doses (0.4 to 4 micrograms/ml) of OMZ produced
      the formation of a chain or cluster of cells. Thickening of the cell wall and
      accumulation of electrondense vesicles in the wall were clearly observed.
      Development of Golgi-like complex membranous structures in the cytoplasm was the
      most prominent finding. The cytological alteration induced by exposure to a
      higher concentration (40 micrograms/ml) of the drug was characterized by
      disruption of the intracytoplasmic organelles. Our results confirm the strong
      antifungal activity of OMZ against fungal cells.

PMID- 9194039
TI  - Cytokines released by human peripheral blood mononuclear cells inhibit the
      production of early and late cytomegalovirus proteins.
AB  - Cytomegalovirus-infected human fibroblasts are susceptible to lysis by natural
      killer cells and cytotoxic T cells. The purpose of this study was to determine
      whether non-lytic mechanisms might also contribute to the control of
      cytomegalovirus infection. The appearance of cytomegalovirus proteins in infected
      fibroblasts was determined by flow cytometry. Infected fibroblasts incubated with
      peripheral blood mononuclear cells for 3 days expressed less early and late
      proteins than fibroblasts incubated without peripheral blood mononuclear cells.
      Supernatants generated by the cocultivation of peripheral blood mononuclear cells
      with cytomegalovirus-infected fibroblasts inhibited the production of
      cytomegalovirus early and late proteins. The soluble factors in supernatants
      which contributed to the inhibitory effect were identified as interferons alpha,
      beta and gamma, and tumor necrosis factors alpha and beta. The ability of
      supernatants to inhibit the production of cytomegalovirus early protein was
      mimicked by combinations of corresponding recombinant cytokines. The inhibition
      of cytomegalovirus protein production by cytokines produced by peripheral blood
      mononuclear cells may contribute to early containment of cytomegalovirus
      infection.

PMID- 9194040
TI  - Herpes simplex virus-specific IgM, IgA and IgG subclass antibody responses in
      primary and nonprimary genital herpes patients.
AB  - To clarify the humoral immunity in herpes simplex virus (HSV) infection, HSV
      specific IgM, IgA and IgG subclass antibody responses were studied in patients
      with genital herpes: 17 primary, 13 recurrent and 6 nonprimary first episode. A
      total of 181 serum samples serially collected from the patients, 5 per patient
      until 213 days after the onset of disease (on average), were analyzed by an
      enzyme-linked immunosorbent assay. IgG1, IgG3 and IgA were detected in all
      patients with primary and nonprimary infections, whereas IgG4 was detected in 74%
      of only those with nonprimary infections and IgG2 was detected in none. IgM was
      detected in 100% of the patients with primary infections, but also in 68% of
      those with nonprimary infections. IgA showed a peak similar to that of IgM in
      patients with primary infections. No significant difference was observed in the
      detection rate or pattern of antibody responses between the recurrent and
      nonprimary first episode infections, nor between the HSV-1 and HSV-2 infections.
      These findings may be useful to improve the diagnostic potential of HSV serology.

PMID- 9194041
TI  - Genetic control of immune responses to HIV-1 env DNA vaccine.
AB  - We investigated the genetic control of immunoglobulin production and the delayed
      type hypersensitivity (DTH) response produced by an HIV-specific DNA vaccine
      using several strains of mice. Murine antigen-specific immunoglobulin production
      was determined by ELISA. The DTH response was assessed in terms of the footpad
      swelling reaction. All strains of mice, except for B10.RIII and B10.T(6R),
      exhibited strong immunoglobulin production and footpad swelling in response to
      the DNA vaccine. In vitro treatment of lymphoid cells with monoclonal antibodies
      showed that the footpad swelling response was mediated by CD4+8- and Ia- T cells.
      However, CD8+ T cells did not suppress footpad swelling. There was no difference
      in the induction of HIV-specific immunoglobulin production or DTH response
      induced by the DNA vaccine among the strains, suggesting that HIV-specific DNA
      vaccine is useful for immunizing various populations against HIV-1.

PMID- 9194042
TI  - Levels of endogenous interleukin-1, interleukin-6, and tumor necrosis factor in
      congenic mice infected with Borrelia garinii.
AB  - This study describes the levels of interleukin-1 alpha (IL-1 alpha), tumor
      necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) in the sera and
      parenchymal organs of various congenic mouse strains infected with Borrelia
      garinii. A significant elevation of inflammatory cytokine levels was found in the
      organs of C3H/HeN (H-2k) and B10.BR (H-2k) mice but not in those of BALB/c mice
      (H-2d). Focally produced cytokines can contribute to antimicrobial defense
      against these organisms. High levels of IL-1 alpha were observed in the sera of
      C3H/HeN, B10.BR and B10 (H-2b) mice infected with B. garinii and they were
      associated with the presence of spirochetes in the skin. Thus, susceptible mice
      demonstrated a stronger cytokine response than resistant mice. This study
      presents in vivo evidence that B. garinii infection affects the
      immunopathogenesis of Lyme disease.

PMID- 9194043
TI  - Replication of feline syncytial virus in feline T-lymphoblastoid cells and
      induction of apoptosis in the cells.
AB  - Feline syncytial virus (FSV) was isolated from feline peripheral blood
      mononuclear cells of FSV-seropositive cats. When the susceptibility of feline T
      lymphocytes to FSV was examined using three strains of FSV, FSV antigens were
      detected in the FSV-infected T-lymphoblastoid cells. Further, a diversity of
      biological properties, including replication kinetics and syncytia formation, was
      noted among the strains, and condensation of chromatin and the fragmentation of
      cellular DNA were observed in the infected cells. From these data, we conclude
      that FSV is lymphotropic and can induce apoptosis in the lymphocytes.

PMID- 9194044
TI  - Fluoxetine, but not tricyclic antidepressants, potentiates the 5
      hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in
      subjects with major depression or with obsessive compulsive disorder.
AB  - It has been suggested that the clinical efficacy of chronic treatment with
      selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps
      all antidepressants is due to their ability to enhance serotonergic activity. The
      effects of chronic treatment with fluoxetine or tricyclic antidepressants on the
      L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol
      and prolactin (PRL) concentrations were studied in patients with major depression
      or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased
      plasma cortisol and PRL levels in medicated and unmedicated patients with major
      depression or OCD. The L-5-HTP-induced cortisol and PRL responses were
      significantly higher in fluoxetine-treated than in tricyclic-treated or
      unmedicated major depressed patients. The latter two groups did not differ
      significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced
      increases in cortisol and PRL in fluoxetine-treated patients with major
      depression or OCD were not significantly different. The results suggest that
      fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated
      stimulation of cortisol and PRL secretion in humans, consistent with available
      evidence that fluoxetine treatment, but not tricyclic antidepressants, increases
      central serotonergic activity in patients with MD or OCD by a presynaptic
      mechanism.

PMID- 9194045
TI  - Lithium attenuates nerve growth factor-induced activation of AP-1 DNA binding
      activity in PC12 cells.
AB  - This investigation tested if lithium, the primary therapeutic agent for bipolar
      mood disorder, modulated activation of the AP-1 transcription factor in PC12
      cells treated with nerve growth factor (NGF), which induces robust responses in
      these cells. NGF induced large, time-dependent increases in AP-1 DNA binding
      activity. Pretreatment with 5 mmol/L lithium for 24 h reduced AP-1 induction by
      NGF by 42%; shorter treatments and lower concentrations of lithium had smaller
      inhibitory effects on AP-1. This effect of lithium was not limited to AP-1, as it
      also inhibited NGF-induced cyclic AMP responsive element (CRE) DNA binding
      activity. In contrast, activation of AP-1 and CRE by forskolin was unaffected by
      lithium. AP-1 constituent proteins were differentially susceptible to lithium, as
      cJun was reduced by 55%, cFos was unaffected by lithium, and an intermediate
      effect was observed with Jun B. These results reveal that lithium modulates the
      activation of transcription factors in a neuronal cell model, indicating that
      selective regulation of gene expression may contribute to the long term in vivo
      effect of lithium.

PMID- 9194046
TI  - Agonist-promoted down-regulation and functional desensitization in two naturally
      occurring variants of the human serotonin1A receptor.
AB  - We recently reported two naturally occurring polymorphisms of the human
      serotonin1A (5-HT1A) receptor: glycine22-->serine (Ser22) and isoleucine28-
      >valine (Val28) in the putative aminoterminal domain of the receptor. To
      investigate the regulatory properties of these variants, the wild type (WT) and
      variant 5-HT1A receptors were stably expressed in CHO-K1 cells. WT, Ser22, and
      Val28 displayed similar high-affinity binding to [3H]-8-OH-DPAT. Competition
      experiments with 5-HT1A agonists and antagonists demonstrated similar
      pharmacological profiles. Receptor agonist-promoted down-regulation was tested by
      exposure to 100 mumol/L 8-OH-DPAT. After 24-h exposure, WT and Val28 underwent
      59.3 +/- 3.9% and 59.5 +/- 1.4% reduction in receptor density respectively,
      whereas the degree of down-regulation was significantly lower for Ser22 (21.4 +/-
      4.2%). Cell treatment for 24 h with 100 mumol/L 8-OH-DPAT reduced the 5-HT
      induced inhibition of cAMP accumulation by 24.9 +/- 5.1% for WT and 16.4 +/- 0.8%
      for Val28, but only by 4.8 +/- 3% for Ser22. We conclude that the Ser22 variant
      is capable of attenuating agonist-mediated receptor down-regulation and
      desensitization.

PMID- 9194047
TI  - Effects of YM-43611, a novel dopamine D2-like receptor antagonist, on immediate
      early gene expression in the rat forebrain.
AB  - The pharmacological characteristics of two benzamides, YM-43611, a potent and
      selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were
      compared with two reference antipsychotic agents, haloperidol and clozapine, in
      terms of modification of c-fos and related gene expression in the rat forebrain.
      After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg),
      haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was
      employed, and the distributions of Fos-like immunoreactive neurons were compared.
      As was the case for the two reference antipsychotics, the two benzamides enhanced
      c-Fos immunoreactivity in a number of forebrain regions. Specifically, like
      clozapine and nemonapride, YM-43611 significantly increased the number of
      immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In
      contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression
      in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number
      of positive cells in the striatum and nucleus accumbens core, whereas clozapine
      and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive
      cells in the lateral septal nucleus and the diagonal band nucleus, but YM-43611,
      nemonapride, and haloperidol did not. The present findings demonstrate that in
      comparison with three other drugs, YM-43611 has restricted effects on c-fos
      expression in the rat forebrain and is active primarily in the shell region of
      the nucleus accumbens and the islands of Calleja. The ability of YM-43611 to
      block D3 and D4 receptors may contribute to its unique actions on Fos induction.

PMID- 9194048
TI  - Electrophysiological actions of neuropeptide Y and its analogs: new measures for
      anxiolytic therapy?
AB  - Neuropeptide Y (NPY) has neuromodulatory actions on multiple brain functions
      including endocrine, behavioral, and circadian processes. Behavioral studies
      suggest that NPY is a potent anxiolytic; however, little is known about how NPY
      affects general arousal and/or attention states. The present study evaluated the
      effects of NPY on spontaneous brain activity as well as auditory processing by
      using electrophysiological measures. Electroencephalographic (EEG) and event
      related potentials (ERPs) were obtained in awake animals after
      intracerebroventricular administration of NPY (1.0, 3.0 nmol) and two of its
      analogs, active at Y1 (1.0, 3.0 nmol) and Y2 (1.0, 3.0 nmol) receptor sites. NPY
      was found to produce dose-related effects on electrophysiological measures.
      Spectral analyses of the EEG revealed that NPY produced slowing of delta activity
      (1-2 Hz) in the frontal cortex and high frequency theta activities (6-8 Hz)
      concomitant with a speeding up of low frequency theta (4-6 Hz) in cortex,
      hippocampus, and amygdala. At higher doses (3.0 nmols) in addition to shifts in
      frequency, EEG power was also significantly reduced in all frequencies (0.5-50
      Hz) in cortex, and in the higher frequencies (8-32 Hz) in the amygdala. The Y1
      and Y2 agonists had a somewhat different profile of EEG effects than the parent
      compound. At the 1 nmol dose both agonists were found to produce selective
      depressions in power in the hippocampus. The 3.0 nmols dose of the Y1 agonist
      produced decreases in EEG stability, an effect commonly produced by anxiolytic
      drugs, whereas the Y2 agonist produced increases in EEG stability in cortex and
      amygdala. Auditory processing, as assessed by ERPs, was affected most
      significantly in the frontal cortex where dose-dependent decreases in the N1
      component of the ERP, a finding also commonly seen after anxiolytics, was found.
      Y1 and Y2 agonists were also found to significantly reduce the amplitude of the
      N1 component of the ERP but less so than the parent compound. The
      electrophysiological and behavioral profiles of NPY and the Y1 agonist resembles
      those of anxiolytics such as ethanol and benzodiazepines. Taken together these
      data suggest that electrophysiological measures of the actions of this peptide
      system may represent a new potentially useful assay for the development of
      anxiolytic drugs.

PMID- 9194049
TI  - Risperidone dose-dependently increases extracellular concentrations of serotonin
      in the rat frontal cortex: role of alpha 2-adrenoceptor antagonism.
AB  - We have previously shown that risperidone, an antipsychotic drug with high
      affinity for 5-hydroxytryptamine (5-HT)2A and dopamine (DA)2 receptors, as well
      as for alpha 2- and alpha 2-adrenoceptors, enhances 5-HT metabolism selectively
      in the rat frontal cortex (FC). To further study the influence of risperidone on
      central 5-HT systems, we compared its effects on dialysate 5-HT in the FC, as
      assessed by microdialysis, with those obtained with other antipsychotic drugs,
      i.e., clozapine, haloperidol, and amperozide, as well as with the selective alpha
      2- or 5-HT2A receptor antagonists idazoxan or MDL 100,907, respectively. The
      underlying mechanism for risperidone's effect on 5-HT output in the FC was also
      investigated using single-cell recording in the dorsal raphe nucleus (DRN).
      Administration of risperidone (0.2, 0.6, and 2.0 mg/kg, SC) dose-dependently
      increased 5-HT levels in the FC. This stimulatory action was mimicked by
      amperozide (10 mg/kg, SC) and, to some extent, by idazoxan (0.25 mg/kg, SC). In
      contrast, clozapine (10 mg/kg, SC), haloperidol (2.0 mg/kg, SC), and MDL 100,907
      (1.0 mg/kg, SC) exerted only minor effects on 5-HT output in brain. Local
      administration of risperidone or idazoxan (1.0-1000 mumol/L) in the FC dose
      dependently increased dialysate levels of 5-HT in this region. On the other hand,
      risperidone 25-800 micrograms/kg, IV) dose-dependently decreased the firing rate
      of 5-HT cells in the DRN, an effect that was largely antagonized by pretreatment
      with the selective 5-HT1A receptor antagonist WAY 100,635 (5.0 micrograms/kg,
      IV). These results indicate that the risperidone-increased 5-HT output in the FC
      may be related to its alpha 2-adrenoceptor antagonistic action, a property shared
      with both amperozide and idazoxan, and that this action probably is executed at
      the nerve terminal level. The inhibition of 5-HT cell firing by risperidone is
      probably secondary to increased 5-HT availability, e.g., in the DRN, since it
      could be antagonized by a 5-HT1A receptor antagonist. The enhanced 5-HT output in
      the FC by risperidone may be of particular relevance for the treatment of
      schizophrenia when associated with depression and in schizoaffective disorder.

PMID- 9194050
TI  - Basic molecular-cellular mechanisms of adaptive responses of the brain.

PMID- 9194051
TI  - Role of neurotrophic factors in adaptational processes of the nervous system.
AB  - Neurotrophic factors (NTF) are low-molecular-weight proteins which epigenetically
      determine neuron survival during embryogenesis and the maintenance of their
      morphofunctional properties in the adult organism. NTF are located in mesenchymal
      tissues and reach neuron bodies by means of retrograde axoplasmic transport in
      nerve fibers; in cell bodies, NTF increase anabolic activity, neurotransmitter
      synthesis, and structural protein production. Neuron cell bodies have two types
      of specialized receptors for binding the most common NTF, nerve growth factor
      (NGF). In the brain, NGF does not affect adrenergic neurons, as it does in the
      periphery, but acts on cholinergic neurons in the basal part of the forebrain.
      The forebrain plays the major role in the processes of learning, memory, and
      plasticity, i.e., in the entire complex of adaptational responses of the nervous
      system, and these may thus depend on the biological activities of substances,
      including NTF, in forebrain tissues. An experimental model was developed
      consisting of organotypic co-cultivation of rat hippocampus fragments with chick
      embryo dorsal root ganglia. This model was used to demonstrate that epileptiform
      activity in the hippocampus is associated with increases in NTF release, which
      can be regarded as an adaptive compensatory response to nerve cell damage
      occurring during convulsive activity.

PMID- 9194052
TI  - Molecular-cellular mechanisms of the formation of long-term memory in the edible
      snail.
AB  - This short review, based mainly on our own studies, summarizes data on the
      molecular-cellular mechanisms of non-associative and associative forms of
      learning (sensitization and classical conditioning) in the edible snail. A
      hypothesis is proposed which suggests that learning in defensive behavior command
      neurons in the edible snail is activated by a complex metabolic response specific
      for the type of conditioned habit. Excitation arriving at the neuron, in addition
      to activating second messenger systems, initiates the synthesis of short-lived (1
      3 h) protein molecules which are specific (in the case of conditioning) or
      relatively specific (in the case of sensitization) for particular synaptic
      inputs. When training is inadequate, its effect can disappear from the point at
      which these proteins are degraded. When learning is better fixed, its effects
      last for several days (for sensitization) or significantly longer periods of time
      (for conditioning). Prolonged retention of habits should correspond to the
      situation of self-maintaining synthesis of long-lived protein molecules, which
      control the synthesis of synapse-specific short-lived regulator molecules.

PMID- 9194053
TI  - Conditioned defensive reflex in the edible snail (molecular-genetic aspects).
AB  - The expression of the early genes c-fos and c-jun were studied by blot
      hybridization in the central nervous system of the edible snail at the
      consolidation stage of a conditioned defensive reflex, with the aim of
      investigating genomic activity in neurons during learning. The c-fos gene was
      shown to be present in the Helix central nervous system, and its expression was
      shown to increase significantly during learning. Superinduction of the c-fos gene
      was observed in the presence of cycloheximide, a protein synthesis inhibitor.
      Corasol also induced this gene. Thus, induction of the c-fos gene in Helix can be
      induced by agents which induce it in higher vertebrates. This suggests that
      expression of the c-fos gene in Helix and in higher vertebrates is regulated by
      closely related mechanisms. Expression of the c-jun gene was insignificant, and
      definitive conclusions with regard to the role of this gene in learning cannot be
      drawn.

PMID- 9194054
TI  - Number of correlates of membrane metabolism and long-term potentiation in rat
      brain slices.
AB  - Long-term potentiation was elicited in living slices of rat olfactory cortex by
      stimulation of the lateral olfactory tract. A group of interdependent parameters
      of membrane metabolism was studied, i.e., the kinetics of 45Ca metabolism, lipid
      peroxidation, and antioxidant defense; cytochemical measurements were made of
      Na+, K(+)-ATPase activity in neurons and glial cells; the functional (GTPase)
      activity of G-proteins was also studied. All parameters were compared with the
      bioelectrical activity of slices at three time points after tetanization, i.e., 3
      5, 15, and 30 min. In most cases, regular phasic changes in metabolic parameters
      occurred, and their functional significance is discussed.

PMID- 9194055
TI  - Atropine inhibits associative potentiation in the hippocampus.
AB  - The effects of the muscarinic receptor blocker atropine on associative long-term
      potentiation were studied in the CA1 region of the rat hippocampus. Focal
      excitatory post-synaptic potentials (EPSP) were recorded in living slices. Local
      application of atropine (0.1 mM) significantly inhibited associative long-term
      potentiation (40-60 min after tetanization) in the "weak" input (str. radiatum
      128 +/- 10% compared with 168 +/- 9% in controls). Long-term potentiation at the
      "strong" input (str. oriens) was increased relative to the control (from 137 +/-
      13% to 158 +/- 4%). These results indicate that endogenous acetylcholine aids the
      development of long-term potentiation in synapses with low levels of activation.

PMID- 9194056
TI  - Endogenous regulators of long-term potentiation and depression in rat olfactory
      cortex slices.
AB  - A perfusate collected from tetanized donor slices of rat olfactory cortex was
      separated by ultrafiltration into fractions containing substances with molecular
      weights of less than and greater than 50 kDal. Each fraction was separately
      tested on recipient slices. The fraction with substances of greater than 50 kDal
      elicited long-term depression of focal potentials in recipient slices. The
      fraction with substances of less than 50 kDal mainly induced activation. The
      chemical nature of the factors released during tetanization was studied by
      treating the high-molecular-weight fraction with immobilized trypsin; after
      proteolytic treatment this fraction produced a qualitatively different response
      in recipient slices, suggesting that the active factors were polypeptides. These
      data indicate that donor slice cells release a set of neurohumoral substances,
      probably polypeptides, during tetanization, which are involved in the modulation
      of synaptic plasticity.

PMID- 9194057
TI  - Role of the phosphoinositide signal system and methylation of
      phosphatidylethanolamine in the development of long-term post-tetanic
      potentiation in rats.
AB  - High-frequency stimulation eliciting long-term post-tetanic potentiation of
      neuronal excitation in slices of the rat olfactory cortex was accompanied by
      changes in the metabolism of phospholipid components of cell membranes. At the
      first stage of the development of long-term potentiation (10 min after
      tetanization), there was a reduction in phosphoinositide metabolism. The
      maintenance phase of the potentiated state (30 min after tetanization) was
      associated with a three-fold increase in the incorporation of 14C-labeled groups
      from adenosylmethionine into phosphatidylethanolamine methylation products and
      with normalization of phosphoinositide metabolism. Sixty minutes after
      tetanization, when potentiation had decayed, there was activation of
      phosphoinositide metabolism and the intensity of phosphatidylethanolamine
      methylation returned to the control level. It is suggested that the
      phosphoinositide system plays an important role in the induction of long-term
      potentiation, as well as at the stage of recovery of normal neuronal
      excitability, while the long-term maintenance phase of elevated neuronal
      excitability was associated with long-lasting changes in the level of
      phosphatidylethanolamine methylation. The effect of glutamate receptor agonists
      on the carbachol-stimulated phosphoinositide response in potentiated slices was
      found to differ from that in nonpotentiated slices. The development of the long
      term potentiated state is thus accompanied by a modulatory action of glutamate on
      the phosphoinositide response.

PMID- 9194058
TI  - Intracellular mechanisms of glutaminergic and cholinergic signal transduction in
      the cerebral cortex.
AB  - A complex method was used to study the effects of acetylcholine and glutamine on
      the dynamics of calcium and polyphosphoinositide regulatory system activities
      over prolonged periods of time in the mammalian cerebral cortex, after exposure
      to these substances in baseline conditions and in conditions of developing
      adaptive responses. Adaptive responses were induced by transient hypoxia with
      oxymetacil as an antioxidant. Agonist stimulation of choline and glutamate
      receptors produced prolonged calcium and phosphoinositide responses in cortical
      structures; these had specific characteristics after exposure to glutamate and
      acetylcholine. During the development of adaptive responses, these changes
      underwent significant modifications. The functional importance of these effects
      is discussed.

PMID- 9194059
TI  - Genetic aspects of the mechanisms of learning.
AB  - Published data demonstrating the direct involvement of the genome in processes
      associated with learning are presented. These processes include the
      intensification of protein and RNA synthesis during learning and induction of
      early gene expression during learning. The relationship between consolidation of
      memory traces and protein synthesis is discussed. Along with different types of
      memory needing induction of gene expression for consolidation, some types of long
      term memory are independent of protein synthesis. The use of genetic methods for
      studying the mechanisms of learning and memory is discussed.

PMID- 9194060
TI  - Genetic approaches to the study of memory in insects.
AB  - This article provides a short summary of studies carried out on mutant Drosophila
      with defects in learning ability, including our own experimental data on the role
      of the tryptophan oxygenase gene (this is a key enzyme, and is the first enzyme
      in the tryptophan-ommochrome metabolic pathway) in the inherited determination of
      learning ability and memory in the honey bee. A set of allelic mutations was used
      which inhibit the activity of this enzyme to different extents, resulting in the
      complete lack of kynurenines or particular levels of kynurenine deficiency in the
      mutant organisms. The effects of mutations at the snow locus (snow, s,
      snowlaranja, sla) on the dynamics of memory trace formation after single training
      sessions were studied in the honey bee and were related to the activity of the
      enzyme responsible for hydrolysis of cyclic nucleotides (phosphodiesterase).
      Relationships were found between the level of disruption in the dynamics of
      memory trace formation and changes in kynurenine content and phosphodiesterase
      activity.

PMID- 9194061
TI  - Autosomal mutations in Drosophila which reduce operant learning ability.
AB  - A collection of Drosophila melanogaster mutants was created by insertion of a P
      element into autosomes at a rate of one copy per genome. The abilities of 64
      homozygous P-insertion mutants to produce a form of associative behavior were
      determined. Testing was based on an original paradigm of operant learning:
      interactions between Drosophila individuals when placed in a group situation in
      which the flies learned to inhibit their own activity to avoid punishment in the
      form of conflict with other individuals. Four lines were found in which, like the
      known learning mutants dunce and rutabaga, individuals did not show changes in
      their initial responses to each other. These lines were also studied using other
      paradigms of associative learning.

PMID- 9194062
TI  - Mutational analysis and genetic cloning of the agnostic locus, which regulates
      learning ability in Drosophila.
AB  - P-insertion mutations were obtained and localized by in situ methods at the
      agnostic gene (agn: 1-38.9; 11AB) in Drosophila. All agn mutants showed a wide
      spectrum of pleiotropic effects: an EMS-induced mutation of the agn-ts398
      improved the ability to develop a conditioned defensive response and increased
      the activity of cAMP metabolic enzymes; spontaneous mutation of agnX1 showed
      morphological defects of the brain. P-insertion mutations were used to clone the
      gene; a restriction map of 80 kb in length was determined, and the insertion was
      localized to a fragment of 9 kb.

PMID- 9194063
TI  - Williams syndrome as a model of genetically determined right-hemisphere
      dominance.
AB  - Studies were carried out on the dermatoglyphics (skin ridge marks) on the hands
      of children with Williams syndrome; this is an inherited disease with
      cardiovascular pathology and a characteristic facial phenotype ("elf" facies),
      along with specific mental and cognitive disturbances. The results suggest a
      characteristic dermatoglyphic type with the presence of complex whorls on the
      fingers and a clear predominance of marks of greater complexity on the left hand;
      this is a very rare trait in normal people and in those with other inherited
      nervous system disorders. The features of the dermatoglyphic pattern serve as a
      characteristic marker of a genetically determined state of the human central
      nervous system, and suggests directions for neurophysiological studies of
      children with Williams syndrome as a unique model for analysis of higher nervous
      function in humans.

PMID- 9194065
TI  - Organization of the Drosophila genome in mutants with changes in second messenger
      metabolism and learning ability.
AB  - Mechanisms modifying the structural-functional organization of polytene
      chromosomes were studied in a Drosophila line in which the activating properties
      of calmodulin were altered and learning ability was increased, by treating
      mutants with homeopathic preparations which affect Ca2+ and F- ion metabolism.
      The results indicated a dominant role for Ca2+ ions and calmodulin in determining
      the chromocentric organization of the nucleus. F- ions, which stimulate the
      adenylate cyclase complex, were found not to have a role.

PMID- 9194064
TI  - Use of phenylthiocarbamide for assessing cAMP-dependent resistance to anoxia in
      animals.
AB  - The responses of cats with different levels of taste sensitivity to
      phenylthiocarbamide (PTC) bitters to five-minute hypoxia were studied; PTC
      sensitivity is a genetic marker of the activity of the cAMP system. Animals able
      to perceive PTC showed a number of functional differences, with higher levels of
      resistance to anoxia, than those which could not perceive PTC. The groups showed
      significant differences in the basal cAMP content in the cerebral cortex, and in
      the time course of changes in the cAMP level during anoxia and subsequent
      reoxygenation. It is suggested that these differences result from genetically
      determined features of the cAMP system, which is involved in forming adaptive
      responses.

PMID- 9194066
TI  - Neuroendocrine mechanisms of the formation of adaptive behavior.
AB  - The behavioral and neuroendocrine responses of the body to external changes are
      determined by genetically determined programs of individual development, and are
      established during pre- and post-natal ontogenesis. These responses, however, can
      be changed by stress or administration of corticosteroid hormones in "critical
      periods" of the body's development. Mineralo- and glucocorticoid receptors
      mediate the "inhibition" of particular neuroendocrine or neuromediator systems,
      promoting behavioral modification.

PMID- 9194067
TI  - Interactions between the serotoninergic and noradrenergic systems of the brain
      and their role in the regulation of animal behavior.
AB  - Studies were carried out using DBA/2 mice on the relationship between the
      behavioral effects of antagonists of different types of 5-HT receptors and the
      level of activity of alpha 2-adrenoceptors. The 5-HT1c receptor antagonists
      mianserin (2 mg/kg) and cyproheptadine (2 mg/kg) and the 5-HT2 receptor
      antagonist ketanserin (3 mg/kg) had no effect on movement activity, while the 5
      HT3 and 5-HT4 receptor antagonists zacopride (1 mg/kg) and ICS 205-930 (1 mg/kg)
      reduced movement behavior in intact animals. On a background of treatment with
      the alpha 2-adrenoceptor blocker yohimbine (0.5 mg/kg), mianserin,
      cyproheptadine, and ketanserin inhibited movement activity and significantly
      reduced the sensitivity of animals to audiogenic convulsions. These data indicate
      that administration of alpha 2-adrenoceptor antagonists increases the efficiency
      with which serotonin receptors regulate behavior.

PMID- 9194068
TI  - Population profile of brain asymmetry in rats after intra-amniotic administration
      of vasopressin.
AB  - The effects of intra-amniotic administration of 1-desamino-8-D-arginine
      vasopressin (DDAVP) at 14 days of embryogenesis on movement asymmetry in neonatal
      and mature mongrel white rats were studied. Controls consisted of intact and sham
      operated animals, as well as rats given intra-amniotic saline. The population
      profile of asymmetry was assessed in terms of the tail position of rats aged two
      days, and also in terms of the direction of excursions in a T-maze in three
      months males. The proportion of animals showing asymmetrical tail poses was no
      more than 36% in controls; the ratio of left-asymmetrical and right-asymmetrical
      intact rats was 2:1. DDAVP increased the number of rats with asymmetrical tail
      poses by a factor of 1.5-2.6, and right-asymmetrical individuals became
      predominant. This effect was demonstrated graphically as a bell-shaped dose
      response curve with a peak response at doses of 3 x 10(-8) and 3 x 10(-6) mg. The
      selection probability for the right-hand side of the maze in experimental animals
      was 0.71 +/- 0.06, which was significantly higher than in animals of the three
      control groups, which showed no preference for the direction of excursions. These
      results indicate lateralization of the action of DDAVP in the developing central
      nervous system, leading to a predominance of right-sided motor responses in
      neonatal and mature rats.

PMID- 9194069
TI  - Neurophysiological mechanisms of cortical-subcortical interactions in the
      organization of behavior.
AB  - Experimental data are discussed within the framework of the fundamental areas of
      studies of the neurophysiological mechanisms of behavior. The first of these is
      the study of the activity of individual neurons, which is characterized by
      plastic rearrangements based on synaptic, molecular (neurochemical), and
      submolecular (genetic) processes. The second area is the study of the activity of
      neuron systems, which unite the cells of different microgroups, and of systems
      including neural elements of different brain structures. Data on plastic
      rearrangements of neuronal activity in different structures during different
      types of behavior lead to the conclusion that the brain has special systems of
      relationships which characterize the interactions of blocks of neurons, in which
      the plasticity of a single neuron can maintain the integration processes of the
      whole system. Our own data, along with results of Russian and foreign
      physiological and clinical investigations, suggest that neurons unite into
      different functional blocks at different phases of conditioned reflex behavior,
      thus determining the dominance status of different centers and the vector of a
      purposive behavioral act in a given situation at a given time. Possible
      directions for further basic studies of the interactions between innate and
      phylogenetically acquired functionally specific neuron units are discussed on the
      basis of hypotheses which have been advanced to explain the neurophysiological
      organizational mechanisms of higher brain functions.

PMID- 9194070
TI  - Neuron activity in the monkey striatum during parallel performance of actions.
AB  - Spike activity was recorded from several neurons in the monkey striatum during
      the performance of a complex behavioral program including differentiation of
      conditioned signals of different levels of complexity. The most characteristic
      feature of spike activity in striatal neurons during behavior was found not to be
      the selective involvement of particular neurons in carrying out certain actions,
      but a reflection of behavior as a whole in the form of mosaics of neuron activity
      corresponding to the moments at which particular actions were performed and
      during the intervals between them.

PMID- 9194072
TI  - Dopamine and the reinforcing system of the brain.

PMID- 9194071
TI  - Synchronization processes in the mechanisms of short-term memory in monkeys: the
      involvement of cholinergic and glutaminergic cortical structures.
AB  - Behavioral experiments were carried out in which monkeys had to solve a task
      involving delayed visual discrimination, and activity was simultaneously recorded
      from several neurons of the visual, prefrontal, and lower temporal regions of the
      cortex before and after modification of cholinergic (by systemic infusion of the
      M-cholinoceptor blocker amizil) and glutaminergic (by intracortical perfusion
      with glutaminergic agonists and antagonists, i.e., NMDA, aminophosphonovalerianic
      acid (APV) and aminophosphonobutyric acid (APB)) systems. Amizil and APV reduced
      the duration of short-term information retention and increased the delay before
      the motor response was made. Worsening of these parameters was accompanied by a
      significant level of desynchronization of activity in the groups of neurons
      studied. NMDA and APB improved short-term memory and increased neuron
      synchronization. The role of synchronization of information processes in the
      mechanisms of short-term memory and the involvement of the cholinergic and
      glutaminergic systems are discussed.

PMID- 9194073
TI  - Effects of microinjection of scopolamine into the neostriatum of rats on
      performance of a food conditioned reflex at different levels of fixation.
AB  - Chronic experiments performed on 32 Sprague-Dawley rats using a movement-feeding
      operant reflex (Skinner box) model showed that microinjection of scopolamine into
      the neostriatum had effects on this reflex which depended on the stage of
      learning. In animals with weakly fixed reflexes (prior to reaching the stage of
      memory consolidation), bilateral microinjection of 0.3 microgram of scopolamine
      into the caudate nucleus completely inhibited the reflex for a prolonged period
      of time. When the operant habit was well fixed, bilateral microinjection of the
      same doses of scopolamine into the neostriatum had no effect on the reflex. These
      results suggest that the neostriatum cholinergic system is critically involved in
      forming the motor engram. The cholinergic system of the caudate nucleus either
      takes no part in realizing the well-fixed conditioned reflex movement response
      and/or other forebrain structures are involved in the reflex, compensating for
      the disturbance in neostriatal cholinergic function.

PMID- 9194074
TI  - Inhibition by the pentapeptide YFRKD of complex conditioned reflex activity
      during the ontogenesis of white rats.

PMID- 9194075
TI  - [Tuberculosis of the spine--a retrospective review of the cases treated with
      surgery for the past 30-year in the National Murayama Hospital].

PMID- 9194076
TI  - [Diagnosis and treatment of peripheral nerve tumor].

PMID- 9194077
TI  - [Diagnosis and treatment of entrapment neuropathy].

PMID- 9194078
TI  - Nuclear medicine in the Third World: which way to go?

PMID- 9194079
TI  - Reliability of a simple non-invasive method for the evaluation of 5-HT2 receptors
      using [18F]-setoperone PET imaging.
AB  - Position emission tomography (PET) imaging of 5-HT2 receptors can be potentially
      very useful in investigating neuropsychiatric disorders and their pharmacological
      treatments. [18F]-setoperone, a PET radio-ligand, has been shown to be useful for
      the delineation of 5-HT2 receptors in the cortex. However, there is no available
      data regarding the scan-rescan reliability of this technique. The purpose of this
      study was to assess the reliability of the [18F]-setoperone PET technique for
      assessing the binding potential (Bmax/ Kd) for 5-HT2 receptors. Ten healthy
      subjects had two [18F]-setoperone PET scans on two separate occasions 6-21 days
      apart. The average difference in the 5-HT2 binding potential (BP) as measured on
      the two occasions in the prefrontal, temporal, parietal and occipital region was
      between 5 and 7%. Thus 5-HT2 BP can be measured with a high reliability using a
      non-invasive technique that uses the cerebellum as a reference region. A power
      analysis based on the reliability data suggests that this technique can be used
      to detect within-subject differences of 10% or more, and between-group
      differences of 25% or more, with a reasonable number of subjects. It is concluded
      that [18F]-setoperone can be routinely produced and reliably used for the PET
      imaging of 5-HT2 receptors in clinical situations.

PMID- 9194080
TI  - 99Tcm-MAG3: a sensitive indicator for evaluating perfusion and rejection of renal
      transplants.
AB  - Radionuclide renography has a role in evaluating perfusion of transplanted
      kidneys. In the course of rejection, cortical perfusion decreases before urinary
      excretion changes. Based on the facts that 99Tcm-MAG3 has different
      pharmacokinetics and shows a higher kidney-to-background count ratio than 99Tcm
      DTPA, we postulated that 99Tcm-MAG3 was a sensitive and reproducible agent to
      measure cortical perfusion of transplanted kidneys. To clarify the feasibility of
      using 99Tcm-MAG3 to measure the cortical perfusion index (CPI), sequential
      renography was performed using 99Tcm-DTPA and 99Tcm-MAG3 in 14 patients with
      stable renal transplants, who had changes in serum creatinine concentration of
      less than 50% between the two studies. The CPI was calculated with 99Tcm-DTPA and
      99Tcm-MAG3 and these were then compared and correlated with concurrent serum
      creatinine concentration. The CPI with 99Tcm-MAG3 was 1.43 times that with 99Tcm
      DTPA in patients with changes in serum creatinine concentration equal to or less
      than 20%, and regression analysis revealed that the difference in CPI was larger
      in patients with more severely decreased renal perfusion than in patients with
      normal or mildly decreased renal perfusion. This preliminary study has indicated
      that the CPI with 99Tcm-MAG3 is a sensitive index for detecting changes in renal
      function, and thus is a feasible indicator of cortical perfusion when evaluating
      the rejection of transplanted kidneys.

PMID- 9194081
TI  - 67Ga scintigraphy for the evaluation of recurrences and residual masses in
      patients with lymphoma.
AB  - 67Ga scintigraphy has proven to be of value in the evaluation of patients with
      lymphoma, especially in their management after treatment. In this study, computed
      tomography (CT) and 67Ga scans were compared in 53 patients with lymphoma who had
      previously been treated. Twenty-eight were patients in continuous clinical
      remission in whom recurrence was suspected. The remaining 25 patients were
      studied between 1 and 3 months post-treatment to assess a residual mass. The
      sensitivity for the detection of lymphoma recurrence was 88% for 67Ga, with two
      false-negative results, and 59% for CT, with seven false-negative results. In the
      diagnosis of recurrence, the specificity of 67Ga was 100% and that of CT 72%,
      with three false-positive results. Therapeutic response was assessed in 25
      patients and the ability to predict response to treatment resulted in a
      specificity of 86% for 67Ga and 81% for CT. Treatment failed in four patients, as
      detected by 67Ga scan, whereas CT did not detect any of these. In the remaining
      21 patients who showed good response to treatment, there were three false
      positive results for 67Ga and four for CT. 67Ga scintigraphy can detect relapse
      more accurately and much earlier than CT, as well as diagnose complete remission
      after treatment. Therefore, 67Ga scintigraphy should be used routinely in
      monitoring response to treatment in lymphoma.

PMID- 9194082
TI  - Kawasaki disease evaluated by two-dimensional echocardiogram and dipyridamole
      201Tl-chloride myocardial SPET.
AB  - Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown
      aetiology that affects infants and children, with most patients having myocardial
      involvement. To evaluate the incidence and nature of myocardial involvement, 30
      patients with Kawasaki disease underwent both dipyridamole 201Tl-chloride
      myocardial single photon emission tomography (SPET) and two-dimensional
      echocardiography (2D-Echo), which were performed within 7 days of each other. The
      SPET image of 15 of 30 (50%) patients showed 27 segments with myocardial
      perfusion abnormalities: 6 patients had one or more segments showing
      redistribution; 6 patients had both one or more segments of reverse
      redistribution and redistribution; 2 patients had reverse redistribution; and one
      patient had one redistribution and one fixed defect. Eight of 15 (53.3%) SPET
      abnormalities included reverse redistribution. Of 15 patients with positive SPET,
      13 were male (age 0.3-12 years, mean = 3.55) and 2 were female (age 3-4 years,
      mean = 3.5). The interval between the onset of disease and SPET ranged from 1 to
      594 weeks. Of the 15 patients with a negative SPET, 10 were male (age 0.4-6
      years, mean = 2.08) and 5 were female (age 0.2-5 years, mean = 1.8). The interval
      between the onset of the disease and SPET ranged from 2 to 54 weeks. There were
      no significant differences in age (P = 0.10), sex (P = 0.41) or interval between
      the onset of disease and SPET in the patients with positive SPET and those with
      negative SPET (P = 0.60). With 2D-Echo, 16 (11/15 patients with positive SPET and
      5/15 patients with negative SPET) of 30 (53.3%) patients had demonstrable
      coronary aneurysms. There was no statistical difference (P = 0.4) in the ability
      to detect myocardial abnormalities between SPET and 2D-Echo. Combining SPET and
      2D-Echo, detectability of myocardial involvement was 66.6% (20/30). We conclude
      (1) that more than 50% of the patients' myocardial involvement was expressed by
      the myocardial perfusion status on SPET or by coronary aneurysm on 2D-Echo.
      Combined SPET and 2D-Echo may be of additive benefit for the detection of
      myocardial involvement. All 15 patients with SPET abnormalities had one or more
      segments of redistribution and/or reverse redistribution, indicating myocardial
      ischaemia and/or damaged but viable myocardium.

PMID- 9194083
TI  - Comparison of radiochemical purity control methods for 99Tcm radiopharmaceuticals
      used in hospital radiopharmacies.
AB  - The free fraction of pertechnetate in 99Tcm radiopharmaceuticals has to be tested
      for quality control reasons in line with the European Pharmacopoeia. Such quality
      control is often performed by miniaturized chromatographic methods. There are
      several recommended methods in the literature for quality control of the same
      radiopharmaceuticals, though it is unlikely that all methods are equivalent. Some
      of these methods were compared, taking into account different parameters (spot
      size, time required, analytical artifacts, true separation and shape of the
      chromatographic peaks, ease of handling), to verify the best method for the
      control of each radiopharmaceutical. It would appear that instant thin layer
      chromatography silica gel is the best support for these miniaturized methods,
      using MEK as solvent to check DTPA, DMSA, gluconate, pyrophosphate, medronate and
      phytate; NaCl 20% solution is the best solvent for IDA derivatives, human albumin
      and albumin particles (microspheres, macroaggregates).

PMID- 9194085
TI  - Non-uniform attenuation correction in SPET using a modified conjugate gradient
      reconstruction method.
AB  - We describe a non-uniform iterative attentuation correction method for single
      photon emission tomography (SPET) which uses transmission data. The method was
      derived using the general inverse problem theory. A cost functional which
      includes noise was derived and minimized using a weighted-least-square maximum a
      posteriori conjugate gradient (CG) method. The Hessian of the cost functional was
      modified by adding a noise term. The a priori value of the model data vector was
      neglected. The method was tested in a clinical cardiac SPET perfusion study.
      Prior to the emission scan, blank and transmission scans were acquired and used
      to obtain the non-uniform map of linear attenuation coefficients. The results of
      the study show that the new iterative method has a slightly better convergence
      rate than the standard CG method. Also, the corrected emission slices obtained by
      the new method were less noisy. Noise was measured as rms% and was reduced by a
      factor of 2.3 for the transmission scans and by a factor of 1.9 for the emission
      scans when reconstructed with the new method compared to the CG method. The new
      method provides a stable solution, whereas the standard CG method, for higher
      iterative steps, diverges. There is potential for improvement in the approach
      described here.

PMID- 9194084
TI  - Are three-dimensional surface-shaded SPET images better than planar and coronal
      SPET images in the assessment of regional pulmonary perfusion?
AB  - Although single photon emission tomographic (SPET) imaging has been shown to be
      more sensitive than planar imaging in the diagnosis of pulmonary embolism, it has
      yet to be used routinely in clinical practice. The aims of this study were (1) to
      compare a new three-dimensional surface-shaded version of SPET (3-D SPET) with
      conventional planar imaging and coronal SPET slices, and (2) to evaluate observer
      agreement among these three modalities in the assessment of regional pulmonary
      perfusion. Compared with a consensus score (based on revised PIOPED criteria) of
      29 cases, including nine with a clinical diagnosis of pulmonary embolism, 3-D
      SPET showed the highest number of normal scans, suggesting better specificity
      than planar or coronal SPET images. Five observers evaluated the three image sets
      twice within a 3-6 month period. Agreement with the consensus score was slightly
      better for the second reading and the average perfect agreement was 71-76%. No
      one image set was superior to any other in this respect. In conclusion, the
      number of normal scans using 3-D SPET is significantly greater relative to planar
      and coronal SPET scans as defined by the consensus view. Observer agreement rates
      are very similar with all three modalities.

PMID- 9194086
TI  - Radiopharmaceuticals for the study of inflammatory processes: a review.
AB  - Recent advances in our understanding of the pathophysiology of inflammatory
      processes at the molecular level, combined with progress in radiopharmaceutical
      sciences, has boosted the development of nuclear medicine techniques for the
      diagnosis of infection/inflammation. The use of radiolabelled white blood cells
      has been studied and evaluated in several pathologies and is still the reference
      method. Several alternative approaches, however, have been developed that may, in
      the future, improve the specificity and the ease of use of the technique. For the
      first time, a radiopharmaceutical that may distinguish between sterile and septic
      inflammation, 99Tcm-Infecton, has been developed. Also, monoclonal antibody
      fragments, cytokines and a variety of new synthetic peptides that bind
      specifically to granulocytes have been prepared. Particularly promising appears
      to be the detection of the expression of adhesion molecules by activated
      endothelium as a first-line technique for the detection of inflammatory foci. For
      the diagnosis of autoimmunity and chronic inflammatory processes, important
      progress has also been made. Autoimmunity can now be studied by in vivo detection
      of tissue-infiltrating activated lymphocytes by radiolabelled interleukin-2. A
      radiopharmaceutical for the diagnosis of monocyte infiltration, J001X, is also
      available, and the commercially available Octreoscan holds promise in autoimmune
      and chronic inflammatory diseases. The efforts of the scientific community have
      given us new perspectives in diagnostic nuclear medicine: easier techniques that
      promise better sensitivity and specificity are now also being tested for the
      study of new disease conditions. The results of the clinical trials now in
      progress will determine the future of this challenging and fascinating field and
      the role of nuclear medicine in the management of patients with
      infection/inflammation.

PMID- 9194087
TI  - The influence of two bone agents (99Tcm-pyrophosphate and 99Tcm
      methylenediphosphonate) on quantitative sacroiliac joint scintigraphy.

PMID- 9194088
TI  - Essays from Scotland.

PMID- 9194089
TI  - Some aspects of food choice and availability today.

PMID- 9194090
TI  - The lost art of successful breastfeeding.

PMID- 9194091
TI  - Reasons for and consequences of the low incidence of breast feeding in Scotland.

PMID- 9194092
TI  - Assessment of lifetime patterns of dairy food intake and physical activity.
AB  - Patterns of nutrition and exercise throughout the life span may account for
      differences in health problems of aging. The purpose of this study was to develop
      and validate a simple life span history questionnaire of dairy food intake and to
      assess recalled levels of leisure time physical activity over the life span.
      Volunteers, 98 women and 49 men, completed two nutritional surveys (Criterion
      Questionnaire, ?CRIQ? and Diary Food Index, ?INDX?) and a physical activity
      questionnaire (P-ACTQ) in a test re-test design. The INDX and P-ACTQ consisted of
      a one to four scale (low to high intake). Dairy food intake averaged 1.4 to 2.3
      servings per day with no significant differences in current dairy food intake
      between decade age categories. When compared to their own recalled 20's decade,
      dairy food intake declined slightly with age, except for the 80-89 age group
      which showed an increased intake. Test retest reliability for the INDX was r =
      0.64. Validity of the INDX compared to the CRIQ was r = 0.64. All groups showed a
      decrease in physical activity levels across the life span. The Dairy Food Index
      holds promise as a simple "global" assessment of dairy food intake for the study
      of lifetime trends in advancing our understanding of the role of lifetime habits
      in chronic "lifestyle" diseases.

PMID- 9194093
TI  - Compliance with the Australian Dietary Guidelines in the early 1990's: have
      population-based health promotion programs been effective?
AB  - In an attempt to change the dietary behaviours of the population (and reduce the
      incidence of diet-related disease), governments and health authorities in
      Australia have developed Dietary Guidelines. These guidelines have been
      communicated to the wider society through a range of channels, such as health
      promotion programs and education campaigns. Studies conducted during the 1980's
      suggested that up to 30 percent of the population were engaging in food-related
      behaviours consistent with dietary guideline recommendations, although the extent
      of compliance varied by population sub-group (eg women and high socioeconomic
      groups were more likely to comply). More recent research has suggested that
      compliance with some of the guideline recommendations has increased, although
      disparities between population sub-groups remain. The aim of this present study
      is to determine the extent of compliance with the Australian Dietary Guidelines
      in the early 1990's, and thereby (indirectly) assess the degree to which health
      promotion efforts have affected the dietary behaviours of the population. The
      study is based on a representative sample (n = 403, 80.6% response rate) of
      Brisbane city. Overall, it was estimated that between 40 and 60 percent of the
      population were regularly engaging in food behaviours consistent with guideline
      recommendations. This rate of compliance, however, differed markedly depending on
      the type of behaviour being examined, and it varied significantly (albeit
      modestly) across different population sub-groups. It is concluded that health
      promotion has influenced the population's dietary behaviours, although
      traditional beliefs and attitudes also inform our food behaviours to a
      considerable extent.

PMID- 9194094
TI  - Supply and demand: a framework for explaining variability in dietary intake and
      its impact on data.
AB  - Nutrition has an important relationship with health and illness. One difficulty
      in measuring intake is related to variability. The purpose of this paper is to
      examine 1) the impact of supply and demand on variability in data collected for
      dietary studies and 2) the relationship between data and estimates of usual
      intake. The forces of supply and demand over time generate a consumption curve
      for each food. Two types of consumption curves are identified. One curve is
      horizontal and represents staples that are steadily consumed. The other curve
      exhibits peaks and dips and is unique for each food whose consumption varies with
      time. The measurement of usual intake is discussed in light of these two types of
      curves. Usual intake of foods whose consumption curve is horizontal could be read
      at any time since consumption does not vary with time. For all other foods,
      measuring usual consumption presents problems since the data vary with time. This
      examination indicates that foods whose consumption varies with time have unique
      properties that must be considered when attempting to calculate consumption.
      Suggestions are given to enhance measurement of consumption of these foods.
      Although excellent methodology currently exists for the calculation of intake,
      attention to the force of supply and demand with only serve to strengthen
      existing methods.

PMID- 9194095
TI  - Are bacterial toxins involved in the aetiology of transmissible spongiform
      encephalopathies?

PMID- 9194096
TI  - Intranasal immunization of mice with Echinococcus granulosus surface antigens
      iscoms evokes a strong immune response, biased towards glucidic epitopes.
AB  - The present work describes the preparation and characterization of iscoms from
      tegumental antigens of Echinococcus granulosus protoscoleces, and their use as
      immunogens in mice by intranasal and subcutaneous routes. Iscoms given at 10 mg
      doses evoke a significant antibody response when administered i.n. and a strong
      and long lasting antibody response by s.c. route. The Ag administered i.n. in a
      non-adjuvanted form as a booster was not immunogenic. The i.n. route of
      immunization induced higher IgA serum titre in relation to IgG than the s.c.
      route and antisera of slightly higher avidity. Also, ten fold lower IgG2a/IgG1
      and ten fold higher IgG3/IgG1 ratios were observed for the i.n. protocol compared
      to the s.c. one. Moreover, the mucosal route of immunization induced more
      efficiently antibodies of both isotypes directed to carbohydrate epitopes. The
      differences between immune response generated by i.n. and parenteral
      immunizations should be taken into consideration, particularly in those cases in
      which protective antigens are glycosylated.

PMID- 9194097
TI  - Cellular immunity to merozoite surface protein 2 (FC27 and 3D7) in Papua New
      Guinean children. Temporal variation and relation to clinical and parasitological
      status.
AB  - A prospective study in 207 children aged 0.5-15 years was carried out in a highly
      endemic area of Papua New Guinea to examine the relationship between cellular
      responses to Plasmodium falciparum merozoite surface protein 2 (MSP2) and malaria
      infection and morbidity. In vitro proliferation, IFN-gamma and IL-4 induction
      were measured against two recombinant proteins of MSP2, FC27 and 3D7 as well as
      against a form of the 3D7 MSP2 lacking the central repetitive sequences (d3D7).
      The prevalence of proliferative response was generally low, 6% for FC27, 9% for
      3D7 and 11% for d3D7. A higher prevalence of IL-4 response was obtained being 27%
      for FC27, 34% for 3D7 and 30% for d3D7 while the prevalence of IFN-gamma response
      was 13%, 15% and 18%, respectively. There was no correlation between age and
      proliferative responses; in contrast cytokine production increased with age for
      all three antigens. When proliferation or stimulation of either cytokine was used
      to assess T-cell activation the frequency of responders increased to 39%, 47% and
      46% for FC27, 3D7 and d3D7 respectively. Analysis of the relation of T cell
      responses to concurrent infection and morbidity showed that lymphoproliferative
      response only to d3D7 was significantly associated with parasitaemia; while
      lymphoproliferative responses to all 3 MSP2 antigens were highest in the group of
      clinical malaria cases. There was no significant correlation between
      proliferation or cytokine production to MSP2 and concurrent or subsequent malaria
      morbidity.

PMID- 9194098
TI  - Recognition of Schistosoma mansoni cathepsins B and L by human IgG1 and IgG4
      antibodies.
AB  - Human schistosome infections are chronic in nature and elevated IgG4 levels are
      associated with length of exposure. To examine how structure, localization and
      dynamics of exposure of a protein to the immune system can affect antibody
      isotype expression, specific antibody levels against two Schistosoma mansoni
      recombinant cathepsin molecules were determined in S. mansoni-infected
      individuals. Cathepsin B (rCatB, secreted in the gut) and cathepsin L (rCatL,
      localized in the reproductive structures) were used to determine IgG1 reactivity,
      as a measure of the stimulation of the immune response, and the switch to IgG4 as
      an indicator of the dynamics and rate of presentation to the immune system. Sera
      from three groups of S. mansoni-infected patients were used: individuals with
      life-long exposure in an endemic area in Burundi, a group from a recent endemic
      focus in Senegal, and of acutely infected European travellers. We report for the
      first time the ability of rCatL to trigger an immune response and show distinct
      antibody isotype reactivity between rCatB versus rCatL. Patients harbouring long
      term chronic infections had elevated levels of IgG4 to both antigen, whereas
      individuals infected for less than four years had high IgG4 to rCatB but not to
      rCatL. Acutely infected travellers developed IgG1 to rCatB only. Our results
      demonstrate that an immune response is mounted more rapidly against a cathepsin
      molecule secreted in the gut of the worm than against an internally localized
      cathepsin.

PMID- 9194099
TI  - Sequential nucleic acid and recombinant adenovirus vaccination induces host
      protective immune responses against Taenia ovis infection in sheep.
AB  - Sheep were immunized with a protective recombinant antigen (45W) from the cestode
      parasite Taenia ovis using three different vaccine delivery systems, either alone
      or in different combinations. The DNA encoding 45W was cloned into the expression
      plasmid pcDNA 3 and an ovine adenovirus to create nucleic acid and recombinant
      viral vector vaccines, respectively. Sheep received two vaccinations with various
      combinations of these two delivery systems and/or purified recombinant 45W
      protein in a conventional vaccine formulation containing Quil A as adjuvant
      (protein/Quil A vaccine). Sheep receiving two inoculations of either the nucleic
      acid or the recombinant adenovirus alone, demonstrated only low levels of 45W
      specific antibody. However, immunization with either nucleic acid or recombinant
      adenovirus primed animals to mount an enhanced immune response after a subsequent
      vaccination with the protein/ Quil A vaccine. The most striking result was that
      sheep initially immunized with the nucleic acid vaccine and boosted with the
      recombinant adenovirus, mounted IgG1 responses > 65 fold higher than those of
      sheep receiving either vaccine alone. The level of antibody in these sheep was
      commensurate with that observed in animals vaccinated twice with the protein/Quil
      A adjuvanted vaccine. In both cases, host-protection from experimental challenge
      infection with T. ovis was obtained.

PMID- 9194100
TI  - Murine Th1 clone defines a 60 kD tachyzoite antigen of Toxoplasma gondii.
AB  - Toxoplasma gondii-specific murine CD4+ T cell clone 3Tx9 belongs to the Th1
      subtype by virtue of secreting high levels of interleukin(IL)-2, interferon-gamma
      and tumor necrosis factor without producing IL4 and IL10. To characterize the
      clonal antigen, Toxoplasma lysate-was separated by SDS-PAGE and probed in T cell
      blot analysis with 3Tx9 T cells, revealing a fraction of about 60 kD molecular
      weight. This fraction proved highly stimulatory also for CD4+ splenocytes
      isolated from infected mice. The expression pattern of the relevant 60 kD antigen
      was determined by challenge of clone 3Tx9 with T. gondii strains from all three
      intraspecies subgroups and tachyzoites versus bradyzoites isolated from two
      strains as a source of antigen. While the T cell clone reacted with tachyzoites
      of all strains tested, bradyzoites lacked antigenic activity. Parallel T cell
      blot and ELISA confirmed co-migration of the T cell-stimulatory antigen p60 and
      rhoptry proteins ROP1, ROP2,3,4, and ROP5 among which ROP1 is a molecule of
      similar size and has only been shown on tachyzoites. However, a ROP1 knock-out
      Toxoplasma mutant still had antigen activity for 3Tx9 T cells. Since the two
      known tachyzoite-specific proteins, surface antigens SAG1/p30 and SAG2/p22, have
      a much lower molecular weight, we suggest that p60 represents a new T. gondii
      tachyzoite marker which is defined by clone 3Tx9.

PMID- 9194101
TI  - Heterogeneity in the recognition of Ostertagia circumcincta antigens by serum
      antibody from mature, infected sheep.
AB  - The recognition of parasite molecules from third-stage and adult Ostertagia
      circumcincta by serum antibody was studied in a group of matched, mature Scottish
      Blackface sheep that had been naturally and then deliberately infected. A total
      of 20 molecules was recognized in somatic extracts from third-stage larvae and 31
      molecules in somatic extracts from adult parasites. However, no sheep recognized
      all immunogenic molecules and no molecule was recognized by all sheep. There was
      no obvious relationship between recognition of any parasite antigen and
      polymorphism at class I loci or at the DRBI class II locus of the major
      histocompatibility complex in these outbred animals. Only 15 molecules from third
      stage larvae were present at a frequency suitable for statistical analysis and
      recognition of three of these 15 molecules was associated with differences in
      worm burdens. Recognition of two of five molecules from adult parasites was
      associated with differences in worm length. These results indicate that variation
      in the recognition of specific, identifiable parasite molecules may be partly
      responsible for variation among sheep in resistance to O. circumcincta.

PMID- 9194102
TI  - Open clinical study of the efficacy and safety of terbinafine cream 1% in
      children with tinea corporis and tinea cruris.
AB  - BACKGROUND: Topical application of antifungal agents is considered the treatment
      of choice for dermatomycoses. Most of the available drugs are fungistatic,
      requiring long term treatment to prevent relapses. Terbinafine is a synthetic
      antifungal agent that, because of its fungicidal action, provides high cure rates
      and low relapse rates after short periods of treatment. METHODS: Ninety-seven
      children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or
      tinea cruris were enrolled in this open trial. After mycologic assessment to
      confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was
      applied once daily during 1 week. Clinical and mycologic assessments were made at
      the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88
      children (9 patients excluded by protocol violation). RESULTS: Therapy was
      considered effective in 92.0% (81 of 88) of patients (complete clinical and
      mycologic cure or mycologic cure with minimum signs and symptoms or clinical
      improvement, > or = 50%). Tolerability was assessed in 97 patients on an
      intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching
      associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1
      of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well
      tolerated treatment for tinea corporis and tinea cruris in children.

PMID- 9194103
TI  - Prevalence of Chlamydia pneumoniae in healthy children and in children with
      respiratory tract infections.
AB  - BACKGROUND: Chlamydia pneumoniae causes respiratory tract infections in adults,
      but little is known about its significance for acute or persistent respiratory
      tract infections in children. METHODS: We studied the prevalence of C. pneumoniae
      by polymerase chain reaction in children younger than the age of 11: 85
      consecutive children with respiratory tract infections; and 93 children presumed
      to be healthy. Throat swabs for PCR analysis were taken from all children, and
      serology was done for 54 of the 85 sick children and from all but one of the
      presumed healthy children positive for C. pneumoniae by PCR. RESULTS: PCR was
      positive in 38 (45%) of the sick children and in 5 (5.7%) of the healthy
      children. All but 2 of 19 sick children with serologic findings suggesting recent
      or ongoing infection with C. pneumoniae were positive by PCR. Most children
      positive for C. pneumoniae by PCR had upper respiratory tract infections. Four
      children had recurrent respiratory tract infections and otitis media with
      effusion treated by tubal insertion. CONCLUSION: The findings suggest that C.
      pneumoniae is common among children with respiratory tract infections.

PMID- 9194104
TI  - Change in nasopharyngeal carriage of Streptococcus pneumoniae resulting from
      antibiotic therapy for acute otitis media in children.
AB  - BACKGROUND: Acute otitis media is the leading reason for antibiotic prescriptions
      in childhood. The increase in antibiotic resistance of Streptococcus pneumoniae
      is generally attributed to the extensive use of antibiotics and the selective
      pressure on the bacterial strains of the nasopharyngeal flora. OBJECTIVE: To
      evaluate the change in nasopharyngeal carriage of S. pneumoniae during antibiotic
      therapy prescribed for acute otitis media. METHODS: Between October, 1993, and
      March, 1994, we conducted a clinical trial comparing cefpodoxime-proxetil and
      amoxicillin-clavulanate in acute otitis media. From 364 children, 4 months to 4.5
      years old, a nasopharyngeal sample was obtained before and after treatment.
      Antibiotic susceptibility was established by determining minimal inhibitory
      concentrations by the agar dilution method. Serotype and randomly amplified
      polymorphic DNA analysis were used to compare pre- and posttreatment S.
      pneumoniae strains. RESULTS: The risk for a child to carry penicillin-resistant
      S. pneumoniae (MIC > or = 0.125 mg/l) did not increase after antibiotic
      treatment: 84 of 364 (23.1%) before, 70 of 364 (19.2%) after. There was a
      significant decrease of penicillin-susceptible S. pneumoniae carriage, 117 of 364
      (32.1%) before treatment compared with 24 of 364 (6.6%) (P = 0.0001) after
      treatment. However, among the children carrying S. pneumoniae at the end of the
      treatment there was an increase in the percentage of penicillin-resistant
      pneumococci: 84 of 201 (41.8%) before treatment and 70 of 94 (74.5%) after
      treatment. Among the 94 children carrying S. pneumoniae at the end of the
      treatment, 22 did not harbor pneumococcus before, 16 carried another
      genotypically different serotype and 56 harbored the same serotype. Among these
      56 children 2 patients harbored strains that had increased MICs for the tested
      beta-lactam antibiotics. The randomly amplified polymorphic DNA analysis showed
      that in one case, the strains were genetically different. CONCLUSIONS: These data
      illustrate that antibiotic therapy did not increase the rate at which children
      carried penicillin-resistant S. pneumoniae, but there was an increase in the rate
      of resistance among the children carrying pneumococci at the end of the
      treatment, mainly as a result of reduction of susceptible strains.

PMID- 9194105
TI  - Patterns and determinants of use of antibiotics for acute respiratory tract
      infection in children in China.
AB  - BACKGROUND: Use of antibiotics for acute respiratory infection (ARI) of presumed
      viral etiology is a worldwide problem. The World Health Organization (WHO) has
      provided guidelines for diagnosis and treatment of ARI for developing countries.
      METHODS: Specially trained observers applied the WHO criteria to study the
      diagnosis and treatment of ARI given by 100 randomly selected health care workers
      (HCWs) in a rural county in China. A total of 750 cases of ARI were evaluated.
      RESULTS: Before the parents sought medical care, 47% of children in the county
      hospitals, 25% of those in the townships and 18% of those in the villages had
      already received antibiotics, available without prescription. Among the HCWs
      antibiotic abuse (antibiotics for presumably viral disease) was detected in the
      treatment of 97% of cases, and severe abuse (such as prescription of two
      incompatible antibiotics) was detected in 37%. Most (197 of 200) patients with
      bacterial disease received antibiotics, but inappropriate antibiotic treatment
      (dose or type) was observed in 63% of these cases. HCWs with university training
      and those with higher test scores on knowledge and attitude prescribed
      antibiotics more judiciously than those lacking those attributes. CONCLUSIONS:
      Abuse of antibiotics for ARI is a serious and costly problem in rural China,
      potentially leading to widespread antibiotic resistance. Educating HCWs in the
      management of ARI and proper use of antibiotics has high priority in China.

PMID- 9194106
TI  - Rotavirus infections in young Nicaraguan children.
AB  - BACKGROUND: Rotavirus is an important cause of dehydrating diarrhea in young
      children throughout the world. Knowledge about frequency of reinfections,
      development of immunity to the virus and the possible protective effect of breast
      milk is important, in particular in relation to possible strategies for
      immunization. METHODS: A prospective study of rotavirus infections in a cohort of
      235 infants followed from birth until 2 years of age was performed in Leon,
      Nicaragua. Fecal and serum specimens were collected at specified times, and
      stools were also obtained during episodes of diarrhea. Fecal specimens were
      screened by rotavirus antigen detection and serum and colostral specimens were
      analyzed by isotype-specific rotavirus antibody enzyme-linked immunosorbent
      assay. RESULTS: As judged by anti-rotavirus IgA antibody seroconversion and/or
      demonstration of rotavirus antigen in fecal specimens, > 50% of the babies had
      evidence of past rotavirus infection by the age of 2 months. The total incidence
      of rotavirus infections, including many reinfections, was 0.7 infection/child
      year, of which only 17% were associated with diarrhea. The time from birth to the
      first demonstration of rotavirus in stool samples correlated significantly with
      the concentration of anti-rotavirus IgA antibodies in colostrum. There was also a
      tendency toward a relationship between long duration of breast-feeding and
      asymptomatic infection. CONCLUSIONS: Rotavirus infections are acquired very early
      in infants in Leon, Nicaragua, and reinfections are common. Most infections are
      asymptomatic. Breast milk appears to confer partial protection against rotavirus
      infection, probably mediated by specific IgA antibodies. To be effective
      rotavirus vaccination would probably have to be given at a very early age to
      infants in developing countries.

PMID- 9194107
TI  - Oral ciprofloxacin vs. intravenous ceftazidime plus tobramycin in pediatric
      cystic fibrosis patients: comparison of antipseudomonas efficacy and assessment
      of safety with ultrasonography and magnetic resonance imaging. Cystic Fibrosis
      Study Group.
AB  - BACKGROUND: More data on the efficacy and safety of ciprofloxacin in pediatric
      cystic fibrosis patients are needed. METHODS: One hundred eight pediatric cystic
      fibrosis patients (ages 5 to 17 years) with acute bronchopulmonary exacerbations
      entered a randomized multicenter trial designed to compare the safety and
      efficacy of antipseudomonas therapy with oral ciprofloxacin (15 mg/kg twice
      daily; maximum dosage 750 mg twice daily) or intravenous ceftazidime plus
      tobramycin (CAZ/TM) for 14 days. RESULTS: Clinical improvement was observed in
      93% of patients treated with oral ciprofloxacin and in 96% of those receiving
      parenteral therapy. Transient suppression of Pseudomonas aeruginosa was achieved
      in 63% of patients at the end of the course of iv CAZ/TM therapy and in 24%
      receiving ciprofloxacin. Ultrasound examination and nuclear magnetic resonance
      imaging scans showed no evidence of cartilage toxicity in any of the
      ciprofloxacin-treated patients. Musculoskeletal adverse events were reported with
      similar frequency in the two groups of patients (7% in the group receiving
      ciprofloxacin therapy and 11% in the IV CAZ/TM group). The only sustained
      musculoskeletal symptom was a case of synovitis in a patient receiving parenteral
      CAZ/TM. CONCLUSION: Ciprofloxacin thus appears to be safe and effective for use
      in young patients with bronchopulmonary exacerbation of cystic fibrosis.

PMID- 9194108
TI  - Ureaplasma urealyticum and pulmonary outcome in a neonatal intensive care
      population.
AB  - OBJECTIVE: To determine whether the presence of Ureaplasma urealyticum in the
      respiratory tracts of very low birth weight infants is associated with increased
      risk of pneumonia, radiographic evidence of severe bronchopulmonary dysplasia
      during the second or third week of life (precocious) and oxygen dependency at 36
      weeks of corrected postnatal gestational age. METHODS: From October, 1993, to
      January, 1996, all infants who met the following entry criteria were enrolled in
      the study: birth weights < or = 1500 g; admission to the NICU within 24 h after
      birth; evidence on admission of respiratory distress; and no prior antibiotic
      treatment. Infants were cultured for mycoplasmas, viruses, chlamydiae and aerobic
      and anaeroic bacteria. RESULTS: Ninety-four critically ill newborns constituted
      our study cohort. Within 7 days of birth more infants with U. urealyticum
      infection showed radiographic features of pneumonia (53.1%, 25 of 47) than
      infants without U. urealyticum infection (21.2%, 10 of 47). Infants with U.
      urealyticum were more likely to have radiographic evidence of precocious
      bronchopulmonary dysplasia than those without this isolate (22.5%, 9 of 40 vs.
      2.3%, 1 of 42). The relative risk of oxygen dependency at 36 weeks of corrected
      age in U. urealyticum-positive infants was 11.0 times that in U. urealyticum
      negative infants (95% confidence interval, 1.6 to 75.5). Association of U.
      urealyticum and chronic lung disease at this age was not weakened after
      adjustments were made in a multivariate analysis for other significant risk
      factors including gestational age and presence of a patent ductus arteriosus.
      CONCLUSIONS: Isolation of U. urealyticum from respiratory tracts is associated
      with radiographic changes compatible with pneumonia within 7 days of birth,
      precocious bronchopulmonary dysplasia and severe pulmonary outcome.

PMID- 9194109
TI  - Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis
      B vaccine containing Pre-S1 and Pre-S2 antigens in neonates.
AB  - BACKGROUND: Most of the licensed hepatitis B vaccines produced by recombinant DNA
      contain the S protein component of the hepatitis B virus surface antigen particle
      but lack two important components, Pre-S1 and Pre-S2. These components have
      recently been shown to play an important immunogenic role by enhancing the
      hepatitis B surface antibody (anti-HBs) titers, stimulating response and
      circumventing genetic nonresponsiveness. OBJECTIVE: To assess safety,
      tolerability and immunogenicity in neonates of a novel recombinant HBV vaccine
      (Bio-Hep-B) containing the S, Pre-S1 and Pre-S2 components compared with a
      licensed recombinant vaccine (Engerix-B) containing the S component only.
      METHODS: Healthy neonates were randomized to receive either Bio-Hep-B (2.5
      micrograms/dose) or Engerix-B (10 micrograms/dose) at ages < 24 h, 1 month and 6
      months. Blood was obtained at ages 0, 1, 7 and 12 months. Tolerability was
      assessed by diary cards filled by the parents for 5 successive days after
      immunization. Immunogenicity was assessed by determination of anti-HBs antibody.
      RESULTS: Of 205 neonates 153 were in the Bio-Hep-B group and 52 were in the
      Engerix-B group. Both vaccines were well-tolerated and all infants became
      seroprotected (anti-HBs > 10 mIU/ml). After the first dose a significantly higher
      proportion of neonates seroconverted in the Bio-Hep-B group than in the Engerix-B
      group (83% vs. 34%; P < 0.001); this difference in seroresponse was even more
      pronounced for those achieving seroprotective concentrations (> 10.0 mIU/ml)
      after the first dose: 54% vs. 7%, respectively (P < 0.001). Geometric mean
      concentrations were significantly higher at all points in the Bio-Hep-B group.
      CONCLUSION: Both vaccines were well-tolerated and immunogenic. Bio-Hep-B, despite
      its low dose, was significantly more immunogenic and elicited more rapid antibody
      response. This finding has implication for future vaccine programs in regions
      where maternal screening for hepatitis B virus surface antigen and administration
      of hepatitis B immunoglobulin are not routinely practiced at birth for infants of
      hepatitis B virus carrier mothers.

PMID- 9194110
TI  - Safety and immunogenicity of a bivalent Haemophilus influenzae type b/hepatitis B
      vaccine in healthy infants. Hib-HB Vaccine Study Group.
AB  - OBJECTIVE: To assess the safety, tolerability and immunogenicity of COMVAX, a
      liquid, bivalent Haemophilus influenzae type b-hepatitis B vaccine, containing
      the polyribosylribitol phosphate (PRP)-Neisseria meningitidis outer membrane
      protein complex conjugate used in the Hib vaccine, PedvaxHIB, and the yeast
      derived hepatitis B surface antigen (HBsAg) used in the HB vaccine, RECOMBIVAX
      HB. DESIGN: Eight hundred eighty-two healthy infants, approximately 2 months of
      age, were enrolled in an open, multicenter (n = 11) clinical trial and randomized
      to receive either COMVAX (7.5 micrograms of PRP/5 micrograms of HBsAg in 0.5 ml)
      or concurrent injections of the liquid formulation of PedvaxHIB (P) (7.5
      micrograms of PRP in 0.5 ml) and RECOMBIVAX HB (R) (5 micrograms of HBsAg in 0.5
      ml) at 2, 4 and 12 or 15 months of age. Safety and tolerability were monitored
      after each injection. The serum concentrations of anti-PRP and anti-HBs were
      determined at the time of each vaccination, 2 months after the second vaccination
      and 1 month after the third vaccination. RESULTS: COMVAX was well-tolerated and
      proved to be immunologically comparable with a series of concomitant P+R
      injections. There were no serious adverse experiences attributable to the study
      vaccines. The most commonly reported nonserious adverse experiences were all
      events prelisted on diary cards given to parents. These included generally mild
      and transient signs of inflammation at the injection site (pain/ soreness,
      erythema, swelling/induration), somnolence and irritability. Because children are
      at peak risk of invasive Hib disease during the first year of life, 6 months of
      age (2 months after the second dose of vaccine) was designated the time of
      primary interest with regard to the development of anti-PRP. At that time 94.8%
      of the infants given COMVAX had > 0.15 microgram/ml of anti-PRP and 72.4% had >
      1.0 microgram/ ml, with a geometric mean concentration (GMC) of 2.5
      micrograms/ml, compared with 95.2%, 76.3% and 2.8 micrograms/ml, respectively, in
      recipients of P+R. The third injection given at 12 or 15 months of age induced a
      secondary rise in antibody. The proportions with > 0.15 microgram/ml and > 1.0
      microgram/ml of anti-PRP increased to 99.3 and 92.6%, respectively, and the GMC
      rose to 9.5 micrograms/ml among COMVAX recipients, compared with 98.9%, 92.3% and
      10.2 micrograms/ml in children given concurrent injections of P+R. In contrast to
      Hib few infants in countries with low endemicity of HBV infection are at near
      term risk of exposure to virus. Consequently the anti-HBs response after the last
      dose of vaccine was designated the outcome of primary interest. At 13 to 16
      months of age (1 month after the third dose of vaccine) 98.4% of children given
      COMVAX had a protective anti-HBs concentration of > or = 10 mIU/ml with a GMC of
      4468 mIU/ml, compared with 100% and a GMC of 6944 mIU/ml among children given
      P+R. CONCLUSIONS: COMVAX is well-tolerated by healthy infants and can induce
      immunity against invasive Hib disease and HBV infection using only three
      injections compared with six injections if separate courses of monovalent
      PedvaxHIB and RECOMBIVAX HB are given.

PMID- 9194111
TI  - Clinical manifestations of human immunodeficiency virus infection in Haitian
      children.
AB  - OBJECTIVE: This study was designed to describe the characteristics of HIV-1
      infection in children in Haiti and to assess its impact on morbidity and
      mortality. BACKGROUND: Throughout the developing world the female-to-male ratio
      of HIV-1 infection approaches 1:1, leading to a tremendous burden of vertically
      transmitted HIV-1 infection. The frequency of transmission, progression of
      disease and AIDS-defining clinical illnesses are not as well-described in this
      setting as in the industrial world. METHODS: Children were identified as being
      HIV-1-seropositive from case findings among family members of individuals
      presenting for screening at the GHESKIO Centers in Port-au-Prince, Haiti.
      Children who were seronegative from the same population were also enrolled and
      both groups were followed at regular intervals. The clinical course and illnesses
      associated with HIV infection were documented. RESULTS: Rapid progression to
      symptomatic disease and death was seen and a battery of physical findings enabled
      a clinician over time to assign with high sensitivity and specificity the
      diagnosis of AIDS to a child. Although many findings are similar, the
      presentation of HIV-1 infection in Haiti differed in significant ways from
      observations in the industrial world. In particular signs of malnutrition,
      failure to thrive and tuberculosis were more common in the Haitian population.
      CONCLUSION: Pediatric HIV-1 infection in Haiti differs significantly from the
      illness in the industrial world. Early mortality poses a particular difficulty in
      diagnosing and ascribing mortality to HIV-1 infection.

PMID- 9194112
TI  - Lifetime cost of care for children with human immunodeficiency virus infection.
AB  - BACKGROUND: Knowledge of the cost of care for children with HIV infection is
      necessary to analyze the economic impact of recommendations for universal
      counseling and voluntary HIV testing of pregnant women. OBJECTIVES: To estimate
      the total cost of care for children with HIV infection. METHODS: We performed a
      retrospective cohort study of all 88 children with (n = 29) or at risk for (n =
      59) perinatally acquired HIV infection cared for at Children's Hospital of
      Wisconsin between February 2, 1987, and June 1, 1995. Review of medical records
      for all 29 children with perinatally acquired HIV infection or AIDS identified:
      date of HIV diagnosis; date of classification into Category N, A, B or C; date of
      AIDS diagnosis; and date of death or transfer of care. The time each subject
      remained in each CDC category was calculated and the Kaplan-Meier product-limit
      method was used to calculate survival time for all patients in each CDC category.
      Hospital-based inpatient and outpatient charges per patient per month in each CDC
      category (N, A, B, C and AIDS) were calculated with information from the hospital
      financial services database, and lifetime hospital-based inpatient and outpatient
      charges were estimated as the sum of the charges for each category. From that,
      total charges were calculated assuming that hospital-based charges were 83% of
      total charges. RESULTS: Based on a median survival time of 120 months, the mean
      lifetime charges for hospital-based care for children with HIV infection was
      $408307 (estimates ranged from $172217 to $498539). If hospital-based care
      represents 83% of the total charges for care of children with HIV infection, then
      mean total lifetime charges for care of children with HIV infection were $491936
      ($207490 to $600649). CONCLUSIONS: The care of children with HIV infections is
      expensive. This information may be useful in planning for care programs and for
      analyzing the economic impact of recommendations for universal counseling and
      voluntary HIV testing of pregnant women.

PMID- 9194113
TI  - Toxoplasmosis of the central nervous system in non-human immunodeficiency virus
      infected children: case report and review of the literature.

PMID- 9194114
TI  - Cost and wastage of antibiotic suspensions: a comparative study for various
      weight groups.

PMID- 9194115
TI  - Comparative trial of two dosages of zalcitabine in zidovudine-experienced
      children with advanced human immunodeficiency virus disease. Pediatric AIDS
      Clinical Trials Group.

PMID- 9194116
TI  - Modified varicella-like syndrome in children previously vaccinated with live
      attenuated measles, mumps, rubella and varicella vaccine.

PMID- 9194117
TI  - Viral meningitis in a preadolescent child caused by reactivation of latent herpes
      simplex (type 1).

PMID- 9194118
TI  - Myocarditis with influenza B infection.

PMID- 9194119
TI  - Postoperative group B streptococcal necrotizing fasciitis in a previously healthy
      child.

PMID- 9194120
TI  - Cough and respiratory distress in a two-month-old infant.

PMID- 9194121
TI  - Role of bacterial antigen tests in the diagnosis of invasive bacterial
      infections.

PMID- 9194122
TI  - Overlap between Kawasaki disease and group A streptococcal infection.

PMID- 9194123
TI  - Neonatal meningococcal meningitis.

PMID- 9194124
TI  - The blanching process due to copper vapour laser treatment of port-wine stains.
AB  - We describe the causes and speed of transient blanching during copper vapour
      laser treatment of port-wine stains. Five watts of yellow (578 nm) light from a
      copper vapour laser was scanned over the lesion using a computer controlled
      scanning system. The clinical response of the lesion to treatment is transient
      blanching, followed immediately by erythema. The clinical response of sclerosed
      vessels is different in that an intravascular coagulum is observed. We measure
      the time taken for the lesion to blanch using two methods. First, high-speed
      photography is used to photograph the treatment process. Second, a photodiode
      measures the light re-emitted from the skin. Using illumination times of 3 to 5
      ms and fluences of approximately 10 J cm-2, blanching times varied between 0 and
      33 ms. We conclude that the cause of the transient blanching is not thermal
      denaturation of either collagen or epidermal melanin. Rather it is the rapid
      expulsion of red blood cells from the treated vessels. Our results have caused us
      to commence clinical trials using a new treatment protocol aimed at further
      improving the response of port-wine stains to copper vapour laser treatment.

PMID- 9194125
TI  - Relationship between time-resolved and non-time-resolved Beer-Lambert law in
      turbid media.
AB  - The time-resolved Beer-Lambert law proposed for oxygen monitoring using pulsed
      light was extended to the non-time-resolved case in a scattered medium such as
      living tissues with continuous illumination. The time-resolved Beer-Lambert law
      was valid for the phantom model and living tissues in the visible and near
      infrared regions. The absolute concentration and oxygen saturation of haemoglobin
      in rat brain and thigh muscle could be determined. The temporal profile of rat
      brain was reproduced by Monte Carlo simulation. When the temporal profiles of rat
      brain under different oxygenation states were integrated with time, the
      absorbance difference was linearly related to changes in the absorption
      coefficient. When the simulated profiles were integrated, there was a linear
      relationship within the absorption coefficient which was predicted for fractional
      inspiratory oxygen concentration from 10 to 100% and, in the case beyond the
      range of the absorption coefficient, the deviation from linearity was slight. We
      concluded that an optical pathlength which is independent of changes in the
      absorption coefficient is a good approximation for near-infrared oxygen
      monitoring.

PMID- 9194126
TI  - Calculation of the dose distribution in water from 71Ge K-shell x-rays.
AB  - The dose distribution in water from 71Ge K-shell x-rays (Eave = 9.44 keV) was
      calculated for various source configurations using both analytic and EGS4 Monte
      Carlo calculations. The point source kernel and the buildup factor are presented.
      The buildup factor for a point source in water has been found to increase up to
      about 1.1 as radial distance approaches 1 cm. Comparison between 71Ge and 90Sr/Y
      shows a similarity between their relative dose distribution in water. The dose
      distribution from a disc source was calculated using the EGS4 code and compared
      with the results from analytic calculation. Excellent agreement was observed,
      confirming the validity of analytic calculations. The dose rate at 0.01 cm from a
      71Ge disc source was calculated to be about 1.3 x 10(-5) Gy MBq-1 s-1. Based on
      the results from this study, 71Ge activity of the order of 3.7 x 10(10) Bq
      (approximately 1 Ci) might be necessary to obtain dose rates typical of 90Sr/Y
      ophthalmic applicators. The possibility of using 71Ge as a source of radioactive
      stents was also investigated. A 71Ge stent was modelled as a cylindrical shell
      source and the dose rates were determined by Monte Carlo calculations. Some
      calculated results are compared with published values for a 32P-coated stent. The
      dose rate at 0.01 cm from a 71Ge stent has been calculated to be about 6.5 x 10(
      3) Gy MBq-1 h-1, which is much lower than the reported dose rate at the same
      distance from a 32P-coated stent. However, an initial source activity of the
      order of 3.7 x 10(7) Bq (approximately 1 mCi) would easily result in a typical
      target dose (approximately 24 Gy) needed for intravascular stent applications. In
      conclusion, 71Ge sources could be used as alternatives to beta sources and,
      unlike high-energy (approximately MeV) beta sources, may provide easily
      predictable dose distributions in heterogeneous media and low dose rates, which
      might be beneficial for some clinical applications.

PMID- 9194127
TI  - Monte Carlo and analytical calculation of proton pencil beams for computerized
      treatment plan optimization.
AB  - Proton pencil beams in water, in a format suitable for treatment planning
      algorithms and covering the radiotherapy energy range (50-250 MeV), have been
      calculated using a modified version of the Monte Carlo code PTRAN. A simple
      analytical model has also been developed for calculating proton broad-beam dose
      distributions which is in excellent agreement with the Monte Carlo calculations.
      Radial dose distributions are also calculated analytically and narrow proton
      pencil-beam dose distributions derived. The physical approximations in the Monte
      Carlo code and in the analytical model together with their limitations are
      discussed. Examples showing the use of the calculated set of proton pencil beams
      as input to an existing photon treatment planning algorithm based on biological
      optimization are given for fully 3D scanned proton pencil beams; these include
      intensity modulated beams with range shift and scanning in the transversal plane.

PMID- 9194128
TI  - What is the explanation for the changes to cobalt-60 tissue-air ratios in BJR
      Supplement 25?
AB  - Values of tissue-air ratio (TAR) in the recent British Journal of Radiology (BJR)
      Supplement 25 have been increased by nearly 2% over the values which have been
      accepted for the past 30 years. The need for this was shown by analysis of
      previous data using scaling laws, together with Monte Carlo calculations and
      careful re-measurement. However, it was not clear why previous determinations of
      TAR were in error: it was not, as some workers argued, because scattered
      radiation had been included in the absorbed dose in the miniphantom, because TAR
      data in BJR Supplement 17 had been derived from peak scatter factor (PSF), which
      is not based on the miniphantom concept. The purpose of this paper is to find the
      real explanation of why the PSF and, therefore, TAR were underestimated for so
      long. Two definitions of PSF are considered: one based on kerma and one based on
      dose. This paper relates PSF of either definition to measurements of air kerma by
      including in the derivation the scatter in the plug which replaces the chamber
      when it has been removed from the surface of the water phantom. The kerma-based
      PSF is found to be 2% higher than the simple ratio of chamber readings in phantom
      and in air. The value of the dose-based definition agrees with that of the kerma
      based definition to within 0.2%. It is the scatter in the replacement plug in the
      surface of the water phantom which was effectively ignored by previous workers,
      and which explains the underestimates of around 2% in PSF and TAR. The value of
      the dose-based PSF differs slightly from that of the kerma-based PSF because of
      the different distributions of primary and scatter photon fluence.

PMID- 9194129
TI  - Conformal radiotherapy computation by the method of alternating projections onto
      convex sets.
AB  - Synthesis of beam profiles for a given dose prescription is a central problem in
      radiotherapy. Care must be taken in the beam design to expose the tumour volume
      at a high level, to avoid significant irradiation of critical organs, and to
      minimize exposure of all other tissue. Use of the synthesis procedure known as
      alternating projections onto convex sets (POCS) is shown to be a viable approach
      to beam design. POCS is a powerful tool for signal and image restoration and
      synthesis. Convex sets of signals obeying desired constraint sets are first
      specified. Then, by repeated projections onto these sets, convergence is to a
      signal obeying all desired constraints if the constraint sets have a finite
      intersection. In this paper we apply the method of POCS to conformal radiotherapy
      dose computation. The performance of the method is shown through three
      representative examples.

PMID- 9194130
TI  - Design of applicators for a 27 MHz multielectrode current source interstitial
      hyperthermia system; impedance matching and effective power.
AB  - In interstitial heating one of the main requirements for achieving a certain
      elevated temperature in a tumour is that the effective power per applicator
      (Peff), i.e. the power which is actually deposited in the tissue, is sufficiently
      high. In this paper this requirement is discussed for the applicators of the 27
      MHz multielectrode current source (MECS) interstitial hyperthermia (IHT) system.
      To minimize power reflection, the applicator impedance was matched with the
      generator impedance by adjusting the length of the coaxial cable in between.
      Transmission line losses, applicator efficiency and subsequently Peff were
      computed for several applicator types. The actual Peff per electrode was obtained
      from calorimetric measurements. Experiments with RC loads, which can be seen as
      perfect applicators, were performed to investigate the effect of mismatching on
      Peff. Applicator losses were measured for clinically used applicators, both
      single- and dual-electrode, utilizing saline phantoms. A simple spherical tumour
      model, using the effective heat conductivity (keff) to account for heat
      transport, was used to estimate Peff for a given tumour size, implant size and
      applicator density. Computations of Peff of various MECS-IHT electrodes were in
      close agreement with the phantom measurements. Most of the initial generator
      power was absorbed in the transmission line (60-65%). The efficiency of the
      applicators was about 65%. For both single- and dual-electrode applicators the
      effective electrode power was found to be about 1 W. Model calculations show that
      Peff of 1 W is sufficient to reach a minimum tumour temperature of 43 degrees C
      in well perfused tumours (keff = 3 W m-1 degree C-1), using a typical implant
      with 2 cm electrodes and 1.5 cm spacing. Mismatching can considerably affect
      Peff. Both a reduction to almost zero and a two-fold increase are possible.
      However, because the matching theory is well understood, mismatching is not a
      serious problem in clinical practice and can even be used to increase Peff if
      necessary. We conclude that the applicator design and the impedance matching
      method chosen in the MECS system allow heating to temperatures in the therapeutic
      range with implants used in clinical practice.

PMID- 9194131
TI  - The feasibility of measuring bone uranium concentrations in vivo using source
      excited K x-ray fluorescence.
AB  - X-ray fluorescence (XRF) has been demonstrated to be an extremely useful
      technique for measuring trace quantities of heavy metals in various tissues
      within the body. This study investigates the applicability of XRF to the
      measurement of bone uranium concentration. The factors affecting the accuracy and
      minimal detectable concentration of bone uranium in vivo are discussed. The
      system chosen employs a 57Co source to excite the uranium K x-rays, with the
      source and detector in an approximate 180 degrees backscatter geometry relative
      to the sample position. It is demonstrated, with experiment and Monte Carlo
      simulation, that the x-ray to coherent peak ratio is linearly related to
      concentration and is independent of variations in source-sample geometry,
      thickness of overlying tissue and tibia size. Preliminary in vivo measurements
      indicate that this system has a minimum detectable concentration of approximately
      20 micrograms U/g bone mineral which may not be sufficiently precise for a
      monitoring system for occupational workers. Future work will involve attempts to
      enhance this precision through the use of alternative sources for the excitation
      of uranium x-rays as well as possible modifications to the detector and
      electronics.

PMID- 9194132
TI  - Region-specific tritium enrichment, and not differential beta-absorption, is the
      major cause of 'quenching' in film autoradiography.
AB  - Tritium quenching refers to the situation in which estimates of tritium content
      generated by film autoradiography depend on the chemical composition of the
      tissue as well as on the concentration of the radioisotope. When analysing thin
      brain sections, for example, regions rich in lipid content generate reduced
      optical densities on x-ray film compared with lipid-poor regions even when the
      total tissue concentration of tritium in those regions is identical. We
      hypothesize that the dried thickness of regions within sections depends upon the
      relative concentrations and types of lipid within the regions. Areas low in white
      matter dry thinner than areas high in white matter, leading to a relative
      enrichment of tritium in the thinner regions. To test this model, a series of
      brain pastes were made with different concentrations of grey and white matter and
      impregnated with equal amounts of tritium. The thickness of dried sections was
      compared with percentage of white matter and apparent radioactive content as
      determined by autoradiogram analysis. The results demonstrated that thickness
      increased, and apparent radioactivity decreased, with higher percentages of white
      matter. In the second experiment, thickness measurements from dried sections were
      successfully used to correct the apparent radioisotope content of autoradiograms
      created from tritium containing white- and grey-matter tissue slices. We conclude
      that within-section thickness variation is the major physical cause for 'tritium
      quenching'.

PMID- 9194133
TI  - SPECT scatter modelling in non-uniform attenuating objects.
AB  - SPECT quantitation and image contrast are degraded by photon scatter. Water
      equivalent depths (WEDs) have been used by several investigators to model scatter
      responses in non-uniform attenuators. The drawback of this approach is the
      occurrence of undesired fluctuations in the shape of the scatter responses, as is
      shown by measurements. An improvement of the WED method is presented, based on
      the assumption that only a part of the scattering object (the region in the
      'scatter cone') contributes significantly to the detected scatter events. The
      remaining part of the object is treated as a uniform medium. The extension of the
      WED method with extra-conical invariance (WEDECI) is evaluated by projection
      measurements of a phantom with a 99mTc source. Shapes of scatter responses
      predicted by the WEDECI method are found to agree better with the measurements
      than those predicted by conventional WEDs.

PMID- 9194134
TI  - Calculation of single detector efficiencies and extension of the normalization
      sinogram in PET.
AB  - A fast iterative method is presented for calculating single detector efficiencies
      for positron emission tomographs. These efficiencies can be used to extend the
      normalization scan to areas outside that covered by the normalization source. The
      root mean square (rms) error of the calculated single detector efficiencies
      decreases exponentially with the number of iterations. Thirty iterations per
      normalization image are sufficient and take about 1 s on a SUN Classic. The
      geometry factors are composed of factors which only depend on the distance from
      the centre of the field-of-view (FOV) and of factors which show a more complex
      pattern over the normalization sinogram. The geometry factors are specific to
      each scanner. On the ECAT 931 scanner the complex part of the geometry factors
      showed a diamond shaped pattern (caused by the varying sensitivity of single
      detectors in a detector block with varying angle of incidence) and S-shaped
      curves (representing attenuation caused by supporting rods for the ring source).
      The coefficient of variation of the diamond-shaped pattern was 4% for detectors
      farthest from the centre of the FOV. Extensions of the normalization scan may,
      therefore, contain a relative rms error of about 4% if the applied geometry
      factors only take the distance from the centre of the FOV into account.

PMID- 9194135
TI  - The direct calculation of parametric images from dynamic PET data using maximum
      likelihood iterative reconstruction.
AB  - The aim of this work is to calculate, directly from projection data, concise
      images characterizing the spatial and temporal distribution of labelled compounds
      from dynamic PET data. Conventionally, image reconstruction and the calculation
      of parametric images are performed sequentially. By combining the two processes,
      low-noise parametric images are obtained, using a computationally feasible
      parametric iterative reconstruction (PIR) algorithm. PIR is performed by
      restricting the pixel time-activity curves to a positive linear sum of predefined
      time characteristics. The weights in this sum are then calculated directly from
      the PET projection data, using an iterative algorithm based on a maximum
      likelihood iterative algorithm commonly used for tomographic reconstruction. The
      ability of the algorithm to extract known kinetic components from the raw data is
      assessed, using data from both a phantom experiment and clinical studies. The
      calculated parametric images indicate differential kinetic behaviour and have
      been used to aid in the identification of tissues which exhibit differences in
      the handling of labelled compounds. These parametric images should be helpful in
      defining regions of interest with similar functional behaviour, and with FDG
      Patlak analysis.

PMID- 9194136
TI  - Calculated depth dose distributions for proton beams in some low-Z materials.
AB  - The extended use of proton beams in clinical radiotherapy has increased the need
      to investigate the accuracy of dosimetry for this type of beam. As for photon and
      electron beams, Monte Carlo simulations are a useful tool in the study of proton
      dosimetry. The existing proton Monte Carlo code PTRAN developed for dosimetry
      purposes is designed for transport of protons in homogeneous water only. In
      clinical proton dosimetry as well as in treatment conditions several other
      materials can be present, such as plastic phantoms, plastic modulator wheels and
      several materials in ionization chambers. To investigate the transport of protons
      in other media we started from the PTRAN code, and implemented proton transport
      in other materials including heterogeneous systems composed of different
      materials. With this extended code, calculations of depth dose distributions for
      some low-Z materials are performed and compared with those obtained for water.
      The results show that for plastics (PMMA, polystyrene and A150) the depth dose
      characteristics are comparable to those of water. For graphite, air and aluminium
      larger differences are observed. The differences between water and the low-Z
      materials studied here are small but can be important for accurate dosimetry.

PMID- 9194137
TI  - Proton beam dosimetry: a comparison between the Faraday cup and an ionization
      chamber.
AB  - From the theoretical point of view, the Faraday cup (FC) is an absolute
      instrument for fluence measurements of proton beams. As the FC is easily
      manufactured it can be considered an 'in-house' calibration system. Moreover, at
      the moment no national standards for proton dosimetry are available. Up to now
      the experimental tests of these instruments show that much study still has to be
      done to better understand their use in reference dosimetry. To investigate the
      possibility of using an FC as a secondary standard, an FC was jointly designed by
      the 'TERA Collaboration' and 'Centre Antoine-Lacassagne' (Nice, France) to
      evaluate the main parameters of the instrument. A comparison between two FCs of
      different designs--the 'TERA FC' and the 'Nice FC'--and an ionization chamber
      (IC) used for routine proton dosimetry was carried out. Results show that the two
      FCs agree to within 1.5-3.6%. While the differences between FC and IC are larger-
      6% for the 'TERA FC' and 8.2% for the 'Nice FC', the FC giving a lower dose
      evaluation--they follow the same trend shown by the calorimetric measurements.
      The data show that once the beam characteristics are defined, the fluence
      measurements are reproducible and show a good accuracy.

PMID- 9194138
TI  - Errors in three-dimensional doses calculated from a two-dimensional database-
      case report: wedged fields at 6 MV.
AB  - This report discusses the calculation of x-ray doses in three dimensions using a
      treatment planning database which was measured in two dimensions only. It
      concerns the common assumption that wedged field profiles in the non-wedged
      direction are similar to open-field profiles for the same field size and depth.
      It shows the extent to which this assumption can lead to errors in wedge dose
      calculation for both solid and dynamically wedged fields on Varian linear
      accelerators at 6 MV. Finally it shows that this assumption tends to produce more
      accurate results when used to calculate doses for dynamically wedged fields and
      why, even in the wedged direction, some of the simpler treatment planning
      algorithms are more suitable for dynamic wedges than they are for solid wedges.

PMID- 9194139
TI  - Parallel operation of Monte Carlo simulations on a diverse network of computers.
AB  - Monte Carlo simulation methods are frequently used to determine light propagation
      in tissue and x-ray propagation as well as for solving other non-medically
      related problems. Such techniques are computationally slow, with the signal to
      noise ratio improving only as the square root of computation time. We present a
      method for the design of a Monte Carlo program that is capable of running on up
      to 24 computers simultaneously, with there being very few restrictions on the
      computer types as long as they run on a common network. This parallel operation
      is useful when the run time is expected to be long. A mixture of PCs and Sun
      workstations have been successfully used. The program as described was designed
      for the simulation of light transport in tissue, but the technique of achieving
      simple simultaneous execution on a number of different computers could be used
      wherever Monte Carlo techniques are used.

PMID- 9194140
TI  - Comments on 'MTF evaluation of a phosphor-coated CCD for x-ray imaging'.

PMID- 9194141
TI  - Differential effects of dopaminergic drugs on anxiety and arousal in healthy
      volunteers with high and low anxiety.
AB  - 1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG
      theta rhythm in the frontal midline area during performance of a mental task,
      indicates relief from anxiety in humans. 2. The authors examined the effects of
      bromocriptine and sulpiride on anxiety and arousal in 24 male university students
      with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta.
      Subjects were given placebo, 2.5 mg bromocriptine and 100 mg sulpiride in a
      double-blind crossover design. 3. Blood samples were obtained, STAI scores were
      determined, and EEGs were recorded before and during the performance of an
      arithmetic addition task. The test was repeated twice: before and 1 hr after drug
      administration. 4. Bromocriptine reduced the HVA concentration in both groups;
      sulpiride caused an increase in both groups. In the Fm theta group, bromocriptine
      did not alter the appearance time of Fm theta, the state anxiety score or the
      task performance; sulpiride increased the Fm theta amount and reduced the state
      anxiety but did not affect the task performance. In the non-Fm theta group,
      bromocriptine increased the Fm theta duration and reduced the state anxiety score
      but did not influence the task performance, while sulpiride reduced Fm theta and
      increased the state anxiety but had no effect on the task performance. 5. These
      results suggest that the sensitivity of presynaptic D2 receptors is higher in
      high-anxiety subjects compared with low-anxiety subjects, and that anxiolytic
      effects in high-anxiety humans and those in low-anxiety humans may be caused by
      decreased and increased DA activity, respectively. In addition, the stimulation
      of DA function may cause anxiogenic effects in high-anxiety individuals.

PMID- 9194142
TI  - A longitudinal study of cerebrospinal fluid angiotensin-converting enzyme in
      neuroleptic-treated schizophrenia.
AB  - 1. The aim of the study was to replicate our earlier finding of elevated
      cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) in neuroleptic
      treated schizophrenia and to elucidate the correlations between CSF ACE,
      neuroleptic treatment, and psychotic symptoms in a longitudinal study. 2. Levels
      of ACE were measured in CSF and serum from 9 acutely psychotic schizophrenic
      patients at two separate points of time; within a few days of admission and at
      follow-up after 3-4 weeks. CSF ACE was also determined from 9 healthy controls.
      3. The schizophrenic patients showed non-significantly higher levels of CSF ACE
      than the controls. Although a significant clinical improvement was observed and
      the neuroleptic medication was reduced during the follow-up period, there were no
      significant differences in serum or CSF ACE between the two observation points in
      the schizophrenia group.

PMID- 9194143
TI  - Side effects of low dose neuroleptics and their impact on clinical outcome in
      generalized anxiety disorder.
AB  - 1. The present study was designed to determine the impact of neuroleptic side
      effects on clinical outcome in generalized anxiety disorder. 2. 205 outpatients
      entered the study. In an open label design fluspirilene 1.5 mg per week was
      administered for a period of 6 weeks. 3. Consistent with previous studies
      fluspirilene demonstrated again anxiolytic properties and was in general
      tolerated well. 4. However, in responders significantly less side effects were
      observed than in nonresponders. The interaction between tolerability and clinical
      outcome is the main finding of the present study. 5. In conclusion, the data
      suggest, that neuroleptic treatment of generalized anxiety disorder should be
      guided by paying more attention to potential side effects. If under neuroleptic
      treatment of generalized anxiety disorders side effects are observed,
      pharmacotherapy should be discontinued, because this fact predicts an
      unfavourable clinical outcome.

PMID- 9194144
TI  - Effects of rewarding electrical stimulation of lateral hypothalamus on classical
      conditioning of the nictitating membrane response.
AB  - 1. Adult New Zealand albino rabbits were prepared with chronic hypothalamic
      stimulating electrodes and hippocampal recording electrodes. 2. Rabbits were
      restrained and classically conditioned by a tone CS and an airpuff US either
      followed or preceded by a hypothalamic stimulation (HS). Control rabbits were
      conditioned without the HS. 3. It was found that HS following the CS facilitated
      both behavioral and hippocampal responses, while HS preceding the CS inhibited
      them. 4. Enhanced hippocampal learning-related unit firing to the CS may
      represent an early indication of conditioning before the behavioral activity
      produces any observable change.

PMID- 9194145
TI  - The influence of nicardipine and ifenprodil on the brain free arachidonic acid
      level and behavior in hypoxia-exposed rats.
AB  - 1. The effects of the calcium channel blockers, nicardipine and ifenprodil, on
      the brain free arachidonic acid level and learning ability in rats exposed to
      hypoxia were examined. 2. Adult rats were injected with 0.003; 0.01; 0.03; 0.1;
      0.3 or 1.0 mg/kg of tested drugs i.p. Thirty min later the learning ability was
      tested in a passive avoidance task according to the step-through procedure.
      Immediately after the training trial, the animals were subjected to a period of
      oxygen deprivation hypoxia until the loss of the righting reflex. The retention
      trial was carried out 24 hr later. 3. The other groups of animals were pretreated
      with mentioned substances before hypoxia-exposure. Fifteen min after the loss of
      the righting reflex they were decapitated and brains were frozen in liquid
      nitrogen. The brain free arachidonic acid level was quantified by gas
      chromatography. 4. Both nicardipine and ifenprodil were effective in preventing a
      memory decline in hypoxia-exposed rats but did not prevent the accumulation of
      the brain free arachidonic acid in hypoxia-exposed rats. 5. The protective
      effects of both substances in behavioral studies during acute brain damage caused
      by hypoxia could not be explained by the prevention of the increase of the brain
      free arachidonic acid, but by some other mechanism.

PMID- 9194146
TI  - Time-dependent effects of fructose on the modulation of a reactivated memory.
AB  - 1. A passive-avoidance-to-active-avoidance negative transfer paradigm was used to
      investigate systematically the time-dependent effects of fructose on reactivated
      memories in rats. 2. Memory reactivation consisted of re-exposing the rats 24 hr
      after passive-avoidance conditioning to environmental and learning cues present
      during training; post-reactivation injections of fructose (100 mg/kg, sc) or
      saline were followed 24 hr later by active-avoidance (discrimination reversal)
      conditioning. Fructose or saline was administered in the experimental room 0, 2,
      5, or 30 min, or in the colony room 60 min, after reactivation. 3. The results
      showed a time-dependent decrease in the ability of fructose to modulate a
      reactivated memory. 4. These results suggest that the time-dependent effects for
      the modulation of a reactivated memory by fructose (a hexose that does not
      readily pass the blood-brain barrier) and glucose (a hexose that readily passes
      the blood-brain barrier) follow similar trends.

PMID- 9194147
TI  - Influence of exercise and ethanol on cholinesterase activity and lipid
      peroxidation in blood and brain regions of rat.
AB  - 1. This study elucidates the interaction of acute exercise and single ethanol
      intake on cholinergic enzyme and its relationship to lipid peroxidation in the
      blood and brain regions of the rat. 2. Butyrylcholinesterase (BuChE) in plasma
      and acetylcholinesterase (AChE) in brain regions as well as lipid peroxidation
      (MDA) were assayed in 1) sedentary control rats; 2) after acute exercise (100%
      VO2max); 3) ethanol 20% (1.6 gm/kg, p.o.); 4) exercise and then ethanol 20% (1.6
      gm/kg, p.o.). 3. Acute exercise significantly increased BuChE activity (155% of
      control) in plasma and decreased AChE activity (60% of control) in the corpus
      striatum with a significant increase in the striatal MDA level (254% of control).
      Ethanol significantly decreased AChE activity only in striatum (86% of control)
      with a significant increase in striatal MDA level (132% of control). 4. The
      combination of exercise and ethanol 20% (1.6 gm/kg, p.o.) significantly increased
      BuChE activity (123% of control) in plasma, and decreased AChE activity (76% of
      control) in striatum with significant increase in striatal MDA level (147% of
      control). 5. Acute exercise, single ethanol 20% (1.6 gm/kg, p.o.) intake and the
      combination selectively inhibited striatal AChE, and the inhibition was
      correlated with increased lipid peroxidation indicating perturbation of motor
      function. The combination reduced the peripheral stress response caused by
      exhaustive exercise.

PMID- 9194148
TI  - Ritanserin administration potentiates amphetamine-stimulated dopamine release in
      the rat prefrontal cortex.
AB  - 1. Administration of serotonin 5-HT2 receptor antagonists increases the basal
      release of dopamine in the mesocorticolimbic pathway. 2. Treatment with dopamine
      D2 receptor antagonists increases impulse-dependent basal dopamine release in the
      nigrostriatal pathway. D2 antagonists also potentiate carrier-mediated increases
      in DA efflux from this pathway. 3. The present study compared the effects of a 5
      HT2A/C antagonist (ritanserin) and a D2 antagonist (haloperidol) on carrier
      mediated (amphetamine-induced) DA release in the mesocortical system. 4. In vivo
      microdialysis was used to recover extracellular fluid from the medial prefrontal
      cortex of conscious rats. Samples were then assayed for dopamine content by HPLC
      with electrochemical detection. Haloperidol or ritanserin were administered
      systemically (i.p.) 30 min before d-amphetamine (5.0 mg/kg i.p.). 5. Results
      demonstrated that 5.0 mg/kg ritanserin, but not 1.0 mg/kg, potentiated
      amphetamine-induced DA release in the prefrontal cortex. Similar to previous
      findings in the striatum, haloperidol (1.0 mg/kg) also augmented amphetamine
      stimulated DA efflux in the cortex. 6. These results suggest that 5-HT2 and D2
      receptor antagonists increase impulse-mediated dopamine release in the rat
      prefrontal cortex which in turn potentiates carrier-mediated release.

PMID- 9194149
TI  - Modulation of apomorphine-induced stereotyped behavior by cholecystokinin.
AB  - 1. The goal was to verify if central or peripheral sulphated cholecystokinin
      octapeptide (CCK8) injections can modulate apomorphine (APO)-induced stereotyped
      behavior. Experiments were designed to determine the involvement of
      cholecystokinin receptor subtypes as well. 2. Animals which received CCK8
      (0.0725, 0.145 and 14.5 nmol, icv) showed a significant (p < 0.05) decrease in
      APO (0.6 mg/kg, sc)-induced stereotyped behavior. 3. No other statistically
      significant difference was observed among groups. Since ip CCK8 (1.16 or 2.32
      nmol/kg) injections did not interfere with APO-induced stereotypy, the results
      suggest that the CCK8 modulatory effects have a central action. 4. The results
      also suggest that the effects of icv CCK8 were not due to the stimulation of CCK8
      receptors alone since central CCK4 (14.5 or 29.0 nmol) injections did not
      interfere with the expression of stereotypy.

PMID- 9194150
TI  - Effects of kawain and dihydromethysticin on field potential changes in the
      hippocampus.
AB  - 1. The kava-pyrones kawain and dihydromethysticin are constituents of Piper
      methysticum which exert anticonvulsant, analgesic and anxiolytic properties. 2.
      In the present study the effect of these kava-pyrones were tested on field
      potential changes (fp) induced by omission of the extracellular Mg2+, recorded
      from the area CA1 and CA3 of the hippocampal slice preparation of guinea pigs.
      These fp are generated by an activation of NMDA receptors and voltage dependent
      calcium channels. 3. Kawain and dihydromethysticin reduced reversibly the
      frequency of occurrence of fp in a concentration range from 5 to 40 mumol/l and
      10 to 40 mumol/l, respectively. 4. Reduction of the fp frequency after addition
      of subthreshold concentrations of 5 mumol/l kawain and 10 mumol/l
      dihydromethysticin indicated additive actions of both drugs. 5. Since the
      serotonin-1A agonist ipsapirone also exerts anxiolytic effects, subthreshold
      concentrations of kawain or dihydromethysticin were combined with a subthreshold
      concentration of ipsapirone in another set of experiments. Combining kawain and
      ipsapirone or dihydromethysticin and ipsapirone caused a reduction of the rate of
      fp to 0.76 and 0.81 of the baseline value, respectively. 6. The findings suggest
      that (i) single constituents of Piper methysticum may have additive actions, (ii)
      that the two components kawain and dihydromethysticin may enhance the effects of
      the anxiolytic serotonin-1A agonist ipsapirone and (iii) that activation of NMDA
      receptors and/or voltage dependent calcium channels may be involved in the
      elementary mechanism of action of some kava-pyrones.

PMID- 9194151
TI  - Dopamine releasing response in rat striatum to single and repeated
      electroconvulsive shock treatment.
AB  - 1. The effect of electroconvulsive shock (ECS) on extracellular concentration of
      dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA) was examined with the use of in vivo
      microdialysis in rat striatum. 2. Extracellular concentration of DA was markedly
      increased up to 183% after single ECS, and that of DOPAC, HVA and 5-HIAA was also
      significantly increased. The increase after the eighth ECS was attenuated
      compared to their increase soon after the first ECS. After repeated ECS, baseline
      concentration of DOPAC, HVA and 5-HIAA was significantly increased, and baseline
      DA concentration tended to increase. 3. These results suggested that single and
      repeated ECS activated metabolism of DA and 5-hydroxytryptamine in rat striatum.
      Activated metabolism of DA may be responsible for the clinical effect of
      electroconvulsive therapy for parkinsonism.

PMID- 9194152
TI  - Phosphorus-31 magnetic resonance spectroscopic observations in 4 cases with
      anorexia nervosa.
AB  - 1. Brain phosphorus metabolism was examined using phosphorus-31 magnetic
      resonance spectroscopy in 4 patients with anorexia nervosa. 2. In 4 patients
      examined before treatment, phosphodiester (PDE) peak area was significantly
      higher than that in 13 normal females. 3. In 6 data points in 4 patients, lower
      levels of PME were associated with malnutrition reflected by endocrinological
      abnormalities. 4. These data suggest that severe malnutrition in patients with
      anorexia nervosa may result in abnormality in membrane phospholipid metabolism,
      which might be responsible for brain atrophy in anorexia nervosa.

PMID- 9194153
TI  - Neuropsychiatric manifestations following the use of 3,4
      methylenedioxymethamphetamine (MDMA: "Ecstasy").
AB  - 1. The recurring side-effects associated with MDMA consumption are reviewed. 2.
      The recreational use of "Ecstasy" has been implicated in the onset of various
      psychological, neurological, and organic complications. A table has been employed
      to depict the deleterious reactions that have occurred following MDMA ingestion.
      3. An original case report is presented in which an individual developed
      perpetual neuropsychiatric symptomatology after having consumed MDMA. This case
      indicates that MDMA may induce long lasting effects, even after one exposure.

PMID- 9194154
TI  - A model of Plasmodium falciparum lactate dehydrogenase and its implications for
      the design of improved antimalarials and the enhanced detection of parasitaemia.

PMID- 9194155
TI  - An analysis of simultaneous variation in protein structures.
AB  - The simultaneous substitution of pairs of buried amino acid side chains during
      divergent evolution has been examined in a set of protein families with known
      crystal structures. A weak signal is found that shows that amino acid pairs near
      in space in the folded structure preferentially undergo substitution in a
      compensatory way. Three different physicochemical types of covariation 'signals'
      were then examined separately, with consideration given to the evolutionary
      distance at which different types of compensation occur. Where the compensatory
      covariation tends towards retaining the combined residue volumes, the signal is
      significant only at very low evolutionary distances. Where the covariation
      compensates for changes in the hydrogen bonding, the signal is strongest at
      intermediate evolutionary distances. Covariations that compensate for charge
      variations appeared with equal strength at all the evolutionary distances
      examined. A recipe is suggested for using the weak covariation signal to assemble
      the predicted secondary structural elements, where the evolutionary distance,
      covariation type and weighting are considered together with the tertiary
      structural context (interior or surface) of the residues being examined.

PMID- 9194156
TI  - Sequence-structure specificity--how does an inverse folding approach work?
AB  - The inverse folding approach is a powerful tool in protein structure prediction
      when the native state of a sequence adopts one of the known protein folds. This
      is because some proteins show strong sequence-structure specificity in inverse
      folding experiments that allow gaps and insertions in the sequence-structure
      alignment. In those cases when structures similar to their native folds are
      included in the structure database, the z-scores (which measure the sequence
      structure specificity) of these folds are well separated from those of other
      alternative structures. In this paper, we seek to understand the origin of this
      sequence-structure specificity and to identify how the specificity arises on
      passing from a short peptide chain to the entire protein sequence. To accomplish
      this objective, a simplified version of inverse folding, gapless inverse folding,
      is performed using sequence fragments of different sizes from 53 proteins. The
      results indicate that usually a significant portion of the entire protein
      sequence is necessary to show sequence-structure specificity, but there are
      regions in the sequence that begin to show this specificity at relatively short
      fragment size (15-20 residues). An island picture, in which the regions in the
      sequence that recognize their own native structure grow from some seed fragments,
      is observed as the fragment size increases. Usually, more similar structures to
      the native states are found in the top-scoring structural fragments in these high
      specificity regions.

PMID- 9194157
TI  - Two new examples of protein structural similarities within the structure-function
      twilight zone.
AB  - Two three-dimensional protein structural similarities accompanied by slight
      similarities in function are reported to highlight the present difficulties in
      discerning the relationship between structure and function. The similarity
      between the structures of uteroglobin and the CAP domain of haloalkane
      dehalogenase reveals a common four helix hydrophobic ligand binding motif. The
      similarity between the beta-barrel domains of glutaminyl tRNA synthetase and
      domain 1 of glutamine synthetase is accompanied by some similarity in the
      location of nucleotide binding sites and suggests a possible ancient domain
      common to these two proteins involved in the synthesis or binding of glutaminyl
      moieties. The problems raised by these two similarities in the structure-function
      'twilight zone' are discussed.

PMID- 9194158
TI  - Assessment of pseudo-energy potentials by the best-five test: a new use of the
      three-dimensional profiles of proteins.
AB  - We propose a new assessment, called the best-five test, for the pseudo-energy
      potential empirically derived from the protein structural database. The object of
      the test is the three-dimensional (3D) profiles of proteins, which are directly
      connected to the pseudo-energy potentials. In the 3D profile, the fitness of each
      amino acid type is ranked at each residue site of a protein. A site whose native
      residue type is ranked within the best-five out of 20 amino acids is regarded as
      satisfactory and the ratio of the satisfactory sites over all the sites of all
      the proteins examined is indicative of the efficiency of the pseudo-energy
      potential employed. We applied the test to our potential function consisting of
      four terms; side-chain packing, hydration, backbone hydrogen-bonding and local
      conformation, by setting various kinds of definitions for each term. Through this
      test, the validity of the minus average operation is confirmed, where the energy
      level of potential functions is adjusted by referring to the random-environmental
      state of the proteins. Especially in the side-chain packing function, the success
      ratio increases from about 30 to 50% with this operation. Failure without the
      operation is ascribed to bulky hydrophobic residues, which almost always occupy
      higher ranking positions in the 3D profile table. A maximum success ratio of
      55.6% was attained with the final potential set consisting of the above four
      terms. The efficiency of the final set was further checked in the fold
      recognition test for distantly related proteins. The best-five test is a new use
      of the 3D profile table for assessing the ability of the pseudo-energy
      potentials.

PMID- 9194159
TI  - Prediction of protein side-chain conformations by principal component analysis
      for fixed main-chain atoms.
AB  - A method of side-chain prediction without calculating the potential function is
      introduced. It is based on the assumption that similar side-chain conformations
      have a similar structural environment around the side chains. The environment
      information is represented by vectors that were obtained from principle component
      analysis and represented by the variance of positions of main-chain atoms around
      side chains. This information was added to the side-chain library (rotamer
      library) made from X-ray structures. Side-chain conformations were constructed
      using this side-chain library without using potential functions. An optimal
      solution was determined by comparing environmental information with the backbone
      conformation around the side chain to be predicted and native ones in the
      library. The method was performed for 15 proteins whose structures were known.
      The result for the root-mean-square deviation between the predicted and X-ray
      side-chain conformations was approximately 1.5 A (the value for core residues was
      approximately 1.1 A) and the percentage of predicted chi 1 angles correct within
      40 degrees was approximately 65% (75% for the core). The computational time was
      short (approximately 60 s for the prediction of proteins with 200 amino acid
      residues). About 70% of the side-chain conformations were constructed by location
      of the main-chain atoms around the central C beta atom and the average of
      r.m.s.d. was approximately 1.4 A (for core residues the average was approximately
      1.0 A).

PMID- 9194160
TI  - Prediction of protein side chain conformations: a study on the influence of
      backbone accuracy on conformation stability in the rotamer space.
AB  - We have studied the effect of backbone inaccuracy on the efficiency of protein
      side chain conformation prediction using rotamer libraries. The backbones were
      generated by randomly perturbing the crystallographic conformation of 12 proteins
      and exhibit C alpha r.m.s.d.s of up to 2 A. Our results show that, even for a
      perturbation of the backbone fully compatible with the temperature factors of the
      proteins, the predicted side chain conformations of approximately 10% of the
      buried side chains remain variable. This fraction increases further for larger
      backbone deviations. However, for backbone deviations of up to 2 A r.m.s.d., the
      predicted side chain r.m.s.d. varies only in a ratio of < 1.4. Moreover, a
      possible strategy for obtaining side chain conformations close to the
      experimental ones consists of extracting the consensus conformations of the side
      chains from a series of backbone conformations. Such a procedure allows the
      computation of the side chain conformations with no loss of accuracy for
      backbones exhibiting r.m.s.d.s of up to 1 A from the crystallographic
      coordinates. For larger backbone deviations (up to 2 A r.m.s.d.) the r.m.s.d. of
      the buried side chains increases from 1.33 up to 1.60 A. We also discuss the
      influence of the size of the rotamer library on the quality of the prediction.

PMID- 9194161
TI  - Protein dynamics determined by backbone conformation and atom packing.
AB  - To study the factors determining the collective motions in thermal,
      conformational fluctuations of a globular protein, molecular dynamics simulations
      were performed with a backbone model and an atomic-level model. In the backbone
      model, only the C alpha atoms were explicitly treated with two types of pairwise
      interactions assigned between the C alpha atoms; atom-packing interactions to
      take into account the effect of tight atom packing in the protein interior and
      chain-restoring interactions to maintain the backbone around the native
      conformation. A quasi-harmonic method was used to decompose the overall
      fluctuations into independent, collective modes. The modes assigned to large
      conformational fluctuations showed a good correlation between the backbone and
      atomic-level models. From this study, it was suggested that the collective modes
      were motions in which a protein fluctuates, keeping the tertiary structure around
      the native one and avoiding backbone overlap and, hence, rough aspects of the
      collective modes can be derived without details of the atomic interactions. The
      backbone model is useful in obtaining the overall backbone motions of a protein
      without heavy simulations, even though the simulation starts from a poorly
      determined conformation of experiments and in sampling main chain conformations,
      from which the side chain conformations may be predicted.

PMID- 9194162
TI  - Comparison of ras-p21 bound to GDP and GTP: differences in protein and ligand
      dynamics.
AB  - This paper documents the first essential dynamics analysis of ras protein ligands
      and of the protein itself, showing important features of their dynamic
      properties. Essential dynamics analysis of 300 ps of full solvent molecular
      dynamics simulations revealed differences in structure and dynamics between GDP-
      and GTP-bound forms of H-ras-p21. Regions in the protein which exhibited a
      structural shift correspond to the switch regions described previously.
      Differences in dynamics between H-ras-p21 GDP and H-ras-p21 GTP may be related to
      interactions of ras with GAP and its receptor and effector. Molecular dynamics of
      free GDP (in the absence of protein) were performed in water for 2 ns and
      analysed using essential dynamics. The conformations of GDP and GTP when bound to
      the protein were compared with free GDP, revealing that the ligands bind to the
      protein in an energetically unfavourable conformation. GDP and GTP molecules from
      various other protein crystal structures were also analysed. These ligands adopt
      similar conformations to those seen in H-ras-p21.

PMID- 9194163
TI  - Computer modelling of the receptor-binding domains of VEGF and PIGF.
AB  - Models of the platelet-derived growth factor (PDGF)-like domains of vascular
      endothelial growth factor (VEGF) and placenta growth factor (PIGF) were built
      based on their homology to PDGF. These domains contain most of the determinants
      for receptor binding. The sequences of these proteins exhibit limited but
      significant homology to that of platelet-derived growth factor (PDGF), a member
      of the cystine knot growth factor family. The eight cysteine residues that are
      involved in intra- and interchain disulphide bonds are conserved. Two high
      affinity receptors for VEGF have been identified, only one of which binds PIGF.
      The models presented here are consistent with results that show that VEGF
      receptor binding is mediated by charged residues in the loops. A comparison of
      the models suggests that the difference in receptor-binding specificity between
      VEGF and PIGF may be due to differences in the distribution of positively charged
      residues and the exposure of hydrophobic residues in the loops.

PMID- 9194164
TI  - Asparagine-127 of xylanase A from Streptomyces lividans, a key residue in
      glycosyl hydrolases of superfamily 4/7: kinetic evidence for its involvement in
      stabilization of the catalytic intermediate.
AB  - Site-directed mutagenesis of asparagine-127 (N127) of xylanase A (XlnA) from
      Streptomyces lividans, belonging to family 10 and superfamily 4/7 of glycosyl
      hydrolases, was chosen to study the role of this conserved residue. The isosteric
      mutation N127D introduced did not affect the fold of XlnA as revealed by circular
      dichroism. Comparison of the kinetic constants of N127D and wild-type XlnA
      revealed a 70-fold decrease in the specificity constant (kcat/K(M)) towards
      birchwood xylan, which is attributed solely to the difference in the kcat value
      and indicates a role of N127 in stabilization of the catalytic intermediate. N127
      also plays a role in maintaining the ionization states of the two catalytic
      residues, as shown by the modified pH profile of XlnA-N127D. Characterization of
      XlnA-N127D and the analysis of the three-dimensional structure of XlnA converge
      towards a stabilization role for N127 in the catalytic site of XlnA.

PMID- 9194165
TI  - The role of the Cys191-Cys220 disulfide bond in trypsin: new targets for
      engineering substrate specificity.
AB  - The S1 binding site of trypsin is cross-linked by the conserved Cys191-Cys220
      disulfide bond. The substitution of Cys191 and Cys220 with Ala decreases the
      activity of trypsin by 20-200-fold as measured by kcat/K(m) for the hydrolysis of
      amide substrates; in contrast, ester hydrolysis is decreased by < 10-fold.
      Similar decreases are observed in the hydrolysis of oligopeptide and single amino
      acid substrates. This decrease in activity results from a decrease in the
      acylation rate. The substrate binding and deacylation rate are not affected by
      the loss of the disulfide bond. C191A/C220A binds BPTI with the same affinity as
      trypsin, although the affinity of benzamidine is decreased 10-fold and the
      affinity of leupeptin is decreased 1000-fold. The CD spectrum of C191A/C220A
      displays significant differences from that of trypsin; these differences most
      likely result from the loss of the disulfide chromophore, although perturbation
      of enzyme structure cannot be discounted. The loss of the Cys191-Cys220 disulfide
      has no effect on the stability of trypsin as measured by urea denaturation.
      Single and double substitutions of Ser at positions 191 and 220 have a similar
      activity to C191A/C220A. These results indicate that the Cys191-Cys220 disulfide
      bond is not essential for the function, structure or stability of trypsin.

PMID- 9194166
TI  - Significance of alpha-fragment of metallothionein in cadmium binding.
AB  - In order to evaluate the significance of alpha- and beta-fragments of
      metallothionein with regard to Cd binding in biosynthetic processes, the Cd
      binding ability of four mutant metallothioneins was examined using the
      Escherichia coli expression system. The features of the mutant metallothioneins
      were proteins in which cysteine residues in the alpha- or beta-fragment were
      replaced with alanine residues, or that the sequential order of the fragments was
      altered. The expressed mutant metallothioneins having an intact alpha-fragment
      showed the constructive abilities of the Cd-thiolate cluster. On the other hand,
      mutant metallothionein having an alpha-fragment lacking metal-binding sites
      exhibited no Cd-binding ability. The condition for maintaining the Cd-binding
      capability of metallothionein was that the alpha-fragment remains intact
      irrespective of the sequential order of the two fragments. The alpha-fragment is
      an indispensable component in metal-binding processes of Cd-metallothionein.

PMID- 9194167
TI  - Analysis of high-affinity binding determinants in the receptor binding epitope of
      basic fibroblast growth factor.
AB  - Basic fibroblast growth factor (bFGF) is implicated in the pathogenesis of
      several vascular and connective diseases. A key step in the discovery of bFGF
      receptor antagonists to mitigate these actions is to define the functional
      epitope required for receptor binding of the growth factor. In previous studies,
      we identified Glu96 as an essential residue in this epitope using site-directed
      mutagenesis. Here we examined the role of solvent accessible neighboring residues
      of Glu96 of bFGF on receptor binding affinity. Wild-type bFGF and its muteins
      were cloned and expressed in Escherichia coli and evaluated for FGF receptor
      binding affinity. Replacement of Asn104 of bFGF by alanine reduced receptor
      binding affinity over 400-fold compared with wild-type bFGF. We next explored the
      effect of neighboring residues of Asn104 on receptor binding affinity-Muteins in
      which Arg97, Leu98, Glu99, Asn101, Asn102, Thr105 and Pro141 were individually
      replaced by alanine exhibited receptor binding similar to wild-type bFGF. By
      contrast, substitution of Tyr103 or Leu140 by alanine reduced receptor binding
      affinity about 400- and 150-fold, respectively, in accord with a previous report.
      We conclude that at least six solvent-accessible residues in bFGF are crucial for
      high-affinity receptor binding, as evidenced by at least a 10-fold diminution in
      the affinity of the corresponding alanine muteins. The polar residues Glu96 and
      Asn104 appear to form an area important for facilitating the initial contact
      between ligand and receptor, whereas Tyr24, Tyr103, Leu140 and Met142 form a
      hydrophobic patch that may stabilize the complex. The detailed structure of this
      functional epitope can be employed in the discovery and design of bFGF
      antagonists using computational methods.

PMID- 9194169
TI  - Disrupting the hydrophobic patches at the antibody variable/constant domain
      interface: improved in vivo folding and physical characterization of an
      engineered scFv fragment.
AB  - By constructing Fv and single-chain Fv (scFv) fragments of antibodies, the
      variable domains are taken out of their natural context in the Fab fragment,
      where they are associated with the constant domains of the light (CL) and heavy
      chain (CH1). As a consequence, all residues of the former variable/constant
      domain interface become solvent exposed. In an analysis of 30 non-redundant Fab
      structures it was found that at the former variable/constant domain interface of
      the Fv fragment the frequency of exposed hydrophobic residues is much higher than
      in the rest of the Fv fragment surface. We investigated the importance of these
      residues for different properties such as folding in vivo and in vitro,
      thermodynamic stability, solubility of the native protein and antigen affinity.
      The experimental model system was the scFv fragment of the anti-fluorescein
      antibody 4-4-20, of which only 2% is native when expressed in the periplasm of
      Escherichia coli. To improve its in vivo folding, a mutagenesis study of three
      newly exposed interfacial residues in various combinations was carried out. The
      replacement of one of the residues (V84D in VH) led to a 25-fold increase of the
      functional periplasmic expression yield of the scFv fragment of the antibody 4-4
      20. With the purified scFv fragment it was shown that the thermodynamic stability
      and the antigen binding constant are not influenced by these mutations, but the
      rate of the thermally induced aggregation reaction is decreased. Only a minor
      effect on the solubility of the native protein was observed, demonstrating that
      the mutations prevent aggregation during folding and not of the native protein.
      Since the construction of all scFv fragments leads to the exposure of these
      residues at the former variable/constant domain interface, this strategy should
      be generally applicable for improving the in vivo folding of scFv fragments and,
      by analogy, also the in vivo folding of other engineered protein domains.

PMID- 9194168
TI  - Single-chain Fv fragments of anti-neuraminidase antibody NC10 containing five-
      and ten-residue linkers form dimers and with zero-residue linker a trimer.
AB  - Single-chain variable fragments (scFvs) of anti-neuraminidase antibody NC10 were
      constructed by joining the VH and VL domains with 10-residue (Gly4Ser)2 and five
      residue (Gly4Ser) linkers; a zero-residue linker scFv was constructed by joining
      the C-terminal residue of the VH domain to the N-terminus of the VL domain. The
      scFv with the 10- and five-residue linkers exclusively formed dimeric antibody
      fragments (M(r) 52000). These were shown to be bivalent and were able to cross
      link two neuraminidase tetramers to form a 'sandwich' type complex; each antigen
      combining site could also bind an anti-idiotype Fab'. The zero-residue linker
      scFv (M(r) 70000) was shown to form a trimer with three active antigen combining
      sites, each binding an anti-idiotype Fab' to yield a complex of M(r) 212000. The
      orientation of the combining sites in the zero-residue linker scFv, however, was
      such that it could not cross-link tetramers of neuraminidase. BIAcore biosensor
      experiments showed that the affinity of each individual antigen combining site in
      both the 10- and five-residue linker scFv dimers and zero-residue linker scFv
      trimer was essentially the same when the scFvs were immobilized onto the sensor
      surface. However, when the scFvs were used as the analyte, the dimeric and
      trimeric scFvs showed an apparent increase in binding affinity due to the avidity
      of binding the multivalent scFvs.

PMID- 9194170
TI  - Two amino acid mutations in an anti-human CD3 single chain Fv antibody fragment
      that affect the yield on bacterial secretion but not the affinity.
AB  - Recombinant antibody fragments directed against cell surface antigens have
      facilitated the development of novel therapeutic agents. As a first step in the
      creation of cytotoxic immunoconjugates, we constructed a single-chain Fv fragment
      derived from the murine hybridoma OKT3, that recognizes an epitope on the epsilon
      subunit of the human CD3 complex. Two amino acid residues were identified that
      are critical for the high level production of this scFv in Escherichia coli.
      First, the substitution of glutamic acid encoded by a PCR primer at position 6 of
      VH framework 1 by glutamine led to a more than a 30-fold increase in the
      production of soluble scFv. Second, the substitution of cysteine by a serine in
      the middle of CDR-H3 additionally doubled the yield of soluble antibody fragment
      without any adverse effect on its affinity for the CD3 antigen. The double mutant
      scFv (Q,S) proved to be very stable in vitro: no loss of activity was observed
      after storage for 1 month at 4 degrees C, while the activity of scFv containing a
      cysteine residue in CDR-H3 decreased by more than half. The results of production
      yield, affinity, stability measurements and analysis of three-dimensional models
      of the structure suggest that the sixth amino acid influences the correct folding
      of the VH domain, presumably by affecting a folding intermediate, but has no
      effect on antigen binding.

PMID- 9194171
TI  - Production of correctly folded recombinant [13C, 15N]-enriched guinea pig [Val90]
      alpha-lactalbumin.
AB  - The M90V mutant of guinea pig alpha-lactalbumin (gpLA) was expressed
      intracellularly in Escherichia coli using a gpLA gene fusion to the IgG-binding
      ('Z') domain coding sequences of staphylococcal protein A. The fusion protein was
      expressed as an inclusion body, then purified and refolded in vitro; CNBr
      cleavage of the fusion polypeptide yielded native alpha-lactalbumin. The
      recombinant M90V gpLA was virtually identical with natural gpLA with respect to
      its ability to stimulate lactose synthesis by galactosyl transferase and the
      recombinant and natural molecules also exhibited similar circular dichroism
      spectra, thermal melting profiles and NMR spectra. However, modest perturbations
      in the chemical shifts of amide protons in the C-helix residues, attributable to
      the Met-->Val mutation, were observed. In defined media, this expression system
      enabled the production of highly-enriched 15N- and 13C, 15N-labeled gpLA. Use of
      this material will allow the solution conformations of the native and molten
      globule states of gpLA to be characterized by high-resolution multidimensional
      NMR.

PMID- 9194172
TI  - Expression and characterization of a cytotoxic human-frog chimeric ribonuclease:
      potential for cancer therapy.
AB  - Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic
      gene encoding the entire protein sequence was constructed by fusing
      oligonucleotides coding for the first 15 and last six of the 104 amino acid
      residues to a genomic clone that encoded the remaining amino acid residues.
      Additionally, the 15 N-terminal amino acid residues of onconase were replaced
      with the first 21 amino acid residues of the homologous human RNase, eosinophil
      derived neurotoxin, EDN. Two versions of the hybrid EDN-onconase protein were
      cloned, expressed and purified. The chimera that contained a glycine in lieu of
      the aspartic acid present in native onconase (position 26 in the chimera)
      exhibited enzymatic activity more characteristic of EDN than native onconase and
      was considerably more active with respect to both RNase activity and cellular
      cytotoxicity than recombinant onconase. In contrast to native or recombinant
      onconase, the EDN chimera was recognized by anti-EDN polyclonal antibodies,
      demonstrating that the chimera also shared structural antigenic determinants to
      the human enzyme. These results demonstrate that a chimeric ribonuclease has
      cytotoxicity comparable to onconase in two out of four cell lines tested. The
      implications with regard to cancer therapy are presented.

PMID- 9194173
TI  - The chemistry and enzymology of the type I signal peptidases.
AB  - The discovery that proteins exported from the cytoplasm are typically synthesized
      as larger precursors with cleavable signal peptides has focused interest on the
      peptidases that remove the signal peptides. Here, we review the membrane-bound
      peptidases dedicated to the processing of protein precursors that are found in
      the plasma membrane of prokaryotes and the endoplasmic reticulum, the
      mitochondrial inner membrane, and the chloroplast thylakoidal membrane of
      eukaryotes. These peptidases are termed type I signal (or leader) peptidases.
      They share the unusual feature of being resistant to the general inhibitors of
      the four well-characterized peptidase classes. The eukaryotic and prokaryotic
      signal peptidases appear to belong to a single peptidase family. This review
      emphasizes the evolutionary concepts, current knowledge of the catalytic
      mechanism, and substrate specificity requirements of the signal peptidases.

PMID- 9194174
TI  - Structural basis for the negative allostery between Ca(2+)- and Mg(2+)-binding in
      the intracellular Ca(2+)-receptor calbindin D9k.
AB  - The three-dimensional structures of the magnesium- and manganese-bound forms of
      calbindin D9k were determined to 1.6 A and 1.9 A resolution, respectively, using
      X-ray crystallography. These two structures are nearly identical but deviate
      significantly from both the calcium bound form and the metal ion-free (apo) form.
      The largest structural differences are seen in the C-terminal EF-hand, and
      involve changes in both metal ion coordination and helix packing. The N-terminal
      calcium binding site is not occupied by any metal ion in the magnesium and
      manganese structures, and shows little structural deviation from the apo and
      calcium bound forms. 1H-NMR and UV spectroscopic studies at physiological ion
      concentrations show that the C-terminal site of the protein is significantly
      populated by magnesium at resting cell calcium levels, and that there is a
      negative allosteric interaction between magnesium and calcium binding. Calcium
      binding was found to occur with positive cooperativity at physiological magnesium
      concentration.

PMID- 9194175
TI  - The uncharged surface features surrounding the active site of Escherichia coli
      DsbA are conserved and are implicated in peptide binding.
AB  - DsbA is a protein-folding catalyst from the periplasm of Escherichia coli that
      interacts with newly translocated polypeptide substrate and catalyzes the
      formation of disulfide bonds in these secreted proteins. The precise nature of
      the interaction between DsbA and unfolded substrate is not known. Here, we give a
      detailed analysis of the DsbA crystal structure, now refined to 1.7 A, and
      present a proposal for its interaction with peptide. The crystal structure of
      DsbA implies flexibility between the thioredoxin and helical domains that may be
      an important feature for the disulfide transfer reaction. A hinge point for
      domain motion is identified-the type IV beta-turn Phe 63-Met 64-Gly 65-Gly 66,
      which connects the two domains. Three unique features on the active site surface
      of the DsbA molecule-a groove, hydrophobic pocket, and hydrophobic patch-form an
      extensive uncharged surface surrounding the active-site disulfide. Residues that
      contribute to these surface features are shown to be generally conserved in eight
      DsbA homologues. Furthermore, the residues immediately surrounding the active
      site disulfide are uncharged in all nine DsbA proteins. A model for DsbA-peptide
      interaction has been derived from the structure of a human thioredoxin:peptide
      complex. This shows that peptide could interact with DsbA in a manner similar to
      that with thioredoxin. The active-site disulfide and all three surrounding
      uncharged surface features of DsbA could, in principle, participate in the
      binding or stabilization of peptide.

PMID- 9194176
TI  - Structural studies of the streptavidin binding loop.
AB  - The streptavidin-biotin complex provides the basis for many important
      biotechnological applications and is an interesting model system for studying
      high-affinity protein-ligand interactions. We report here crystallographic
      studies elucidating the conformation of the flexible binding loop of streptavidin
      (residues 45 to 52) in the unbound and bound forms. The crystal structures of
      unbound streptavidin have been determined in two monoclinic crystal forms. The
      binding loop generally adopts an open conformation in the unbound species. In one
      subunit of one crystal form, the flexible loop adopts the closed conformation and
      an analysis of packing interactions suggests that protein-protein contacts
      stabilize the closed loop conformation. In the other crystal form all loops adopt
      an open conformation. Co-crystallization of streptavidin and biotin resulted in
      two additional, different crystal forms, with ligand bound in all four binding
      sites of the first crystal form and biotin bound in only two subunits in a
      second. The major change associated with binding of biotin is the closure of the
      surface loop incorporating residues 45 to 52. Residues 49 to 52 display a 3(10)
      helical conformation in unbound subunits of our structures as opposed to the
      disordered loops observed in other structure determinations of streptavidin. In
      addition, the open conformation is stabilized by a beta-sheet hydrogen bond
      between residues 45 and 52, which cannot occur in the closed conformation. The
      3(10) helix is observed in nearly all unbound subunits of both the co
      crystallized and ligand-free structures. An analysis of the temperature factors
      of the binding loop regions suggests that the mobility of the closed loops in the
      complexed structures is lower than in the open loops of the ligand-free
      structures. The two biotin bound subunits in the tetramer found in the MONO-b1
      crystal form are those that contribute Trp 120 across their respective binding
      pockets, suggesting a structural link between these binding sites in the
      tetramer. However, there are no obvious signatures of binding site communication
      observed upon ligand binding, such as quaternary structure changes or shifts in
      the region of Trp 120. These studies demonstrate that while crystallographic
      packing interactions can stabilize both the open and closed forms of the flexible
      loop, in their absence the loop is open in the unbound state and closed in the
      presence of biotin. If present in solution, the helical structure in the open
      loop conformation could moderate the entropic penalty associated with biotin
      binding by contributing an order-to-disorder component to the loop closure.

PMID- 9194177
TI  - De novo design of the hydrophobic core of ubiquitin.
AB  - We have previously reported the development and evaluation of a computational
      program to assist in the design of hydrophobic cores of proteins. In an effort to
      investigate the role of core packing in protein structure, we have used this
      program, referred to as Repacking of Cores (ROC), to design several variants of
      the protein ubiquitin. Nine ubiquitin variants containing from three to eight
      hydrophobic core mutations were constructed, purified, and characterized in terms
      of their stability and their ability to adopt a uniquely folded native-like
      conformation. In general, designed ubiquitin variants are more stable than
      control variants in which the hydrophobic core was chosen randomly. However, in
      contrast to previous results with 434 cro, all designs are destabilized relative
      to the wild-type (WT) protein. This raises the possibility that beta-sheet
      structures have more stringent packing requirements than alpha-helical proteins.
      A more striking observation is that all variants, including random controls,
      adopt fairly well-defined conformations, regardless of their stability. This
      result supports conclusions from the cro studies that non-core residues
      contribute significantly to the conformational uniqueness of these proteins while
      core packing largely affects protein stability and has less impact on the nature
      or uniqueness of the fold. Concurrent with the above work, we used stability data
      on the nine ubiquitin variants to evaluate and improve the predictive ability of
      our core packing algorithm. Additional versions of the program were generated
      that differ in potential function parameters and sampling of side chain
      conformers. Reasonable correlations between experimental and predicted
      stabilities suggest the program will be useful in future studies to design
      variants with stabilities closer to that of the native protein. Taken together,
      the present study provides further clarification of the role of specific packing
      interactions in protein structure and stability, and demonstrates the benefit of
      using systematic computational methods to predict core packing arrangements for
      the design of proteins.

PMID- 9194179
TI  - Optimization of the electrostatic interactions between ionized groups and peptide
      dipoles in proteins.
AB  - The three-dimensional optimization of the electrostatic interactions between the
      charged amino acid residues and the peptide partial charges was studied by Monte
      Carlo simulations on a set of 127 nonhomologous protein structures with known
      atomic coordinates. It was shown that this type of interaction is very well
      optimized for all proteins in the data set, which suggests that they are a
      valuable driving force, at least for the native side-chain conformations. Similar
      to the optimization of the charge-charge interactions (Spassov VZ, Karshikoff AD,
      Ladenstein R, 1995, Protein Sci 4:1516-1527), the optimization effect was found
      more pronounced for enzymes than for proteins without enzymatic function. The
      asymmetry in the interactions of acidic and basic groups with the peptide dipoles
      was analyzed and a hypothesis was proposed that the properties of peptide dipoles
      are a factor contributing to the natural selection of the basic amino acids in
      the chemical composition of proteins.

PMID- 9194178
TI  - MultiCoil: a program for predicting two- and three-stranded coiled coils.
AB  - A new multidimensional scoring approach for identifying and distinguishing
      trimeric and dimeric coiled coils is implemented in the MultiCoil program. The
      program extends the two-stranded coiled-coil prediction program PairCoil to the
      identification of three-stranded coiled coils. The computations are based upon
      data gathered from a three-stranded coiled-coil database comprising 6,319 amino
      acid residues, as well as from the previously constructed two-stranded coiled
      coil database. In addition to identifying coiled coils not predicted by the two
      stranded database programs, MultiCoil accurately classifies the oligomerization
      states of known dimeric and trimeric coiled coils. Analysis of the MultiCoil
      scores provides insight into structural features of coiled coils, and yields
      estimates that 0.9% of all protein residues form three-stranded coiled coils and
      that 1.5% form two-stranded coiled coils. The MultiCoil program is available at
      http:/(/)theory.lcs.mit.edu/multicoil.

PMID- 9194181
TI  - Identification of compact, hydrophobically stabilized domains and modules
      containing multiple peptide chains.
AB  - Compactness has been used to locate discontinuous structural units containing one
      or more polypeptide chains in proteins of known structure. Rather than
      exhaustively calculating the compactness of all possible units, our procedure
      uses a screening algorithm to find discontinuous regions that are potentially
      compact. Precise calculations of compactness are restricted only to units in
      these regions. With our procedure, compactness can be used to discover
      discontinuous domains with virtually any number of disjoint peptides. Small,
      single-domain proteins may contain several compact regions: thus, compact regions
      do not always correspond to folding domains. Because a domain is an independent
      folding unit and should contain a hydrophobic core, compact units were further
      examined for the presence of hydrophobic clusters (Zehfus MH, 1995, Protein Sci
      4:1188-1202). This added constraint limits the number of acceptable units and
      helps greatly in the location of the true structural domains. The larger
      hydrophobically stabilized compact units correspond to domains, while the smaller
      units may correspond to folding intermediates.

PMID- 9194180
TI  - Refined structure of villin 14T and a detailed comparison with other actin
      severing domains.
AB  - Villin 14T is the amino terminal actin monomer binding domain from the actin
      severing and bundling protein villin. Its structure has been determined in
      solution using heteronuclear multidimensional nuclear magnetic resonance (NMR)
      spectroscopy (Markus MA, Nakayama T, Matsudaira P, Wagner G. 1994. Solution
      structure of villin 14T, a domain conserved among actin-severing proteins.
      Protein Science 3:70-81). An additional nuclear Overhauser effect (NOE)
      spectroscopy data set, acquired using improved gradient techniques, and further
      detailed analysis of existing data sets, produced an additional 601 NOE
      restraints for structure calculations. The overall fold does not change
      significantly with the additional NOE restraints but the definition of the
      structure is improved, as judged by smaller deviations among an ensemble of
      calculated structures that adequately satisfy the NMR restraints. Some of the
      side chains, especially those in the hydrophobic core of the domain, are much
      more defined. This improvement in the detail of the solution structure of villin
      14T makes it interesting to compare the structure with the crystal structure of
      gelsolin segment 1, which shares 58% sequence identity with villin 14T, in an
      effort to gain insight into villin 14T's weaker affinity for actin monomers.
      Villin 14T has smaller side chains at several positions that make hydrophobic
      contacts with actin in the context of gelsolin segment 1. The structure is also
      compared with the structure of the related actin-severing domain, severin domain
      2.

PMID- 9194183
TI  - Characterization of the receptor binding determinants of granulocyte colony
      stimulating factor.
AB  - We performed a series of experiments using alanine-scanning mutagenesis to locate
      side chains within human granulocyte colony-stimulating factor (G-CSF) that are
      involved in human G-CSF receptor binding. We constructed a panel of 28 alanine
      mutants that examined all surface exposed residues on helices A and D, as well as
      all charged residues on the surface of G-CSF. The G-CSF mutants were expressed in
      a transiently transfected mammalian cell line and quantitated by a sensitive
      biosensor method. We measured the activity of mutant proteins using an in vitro
      proliferation assay and an ELISA binding competition assay. These studies show
      that there is a region of five charged residues on helices A and C employed by G
      CSF in binding its receptor, with the most important residue in this binding
      patch being Glu 19. Both wild-type G-CSF and the E19A mutant were expressed in E.
      coli. The re-folded proteins were found to have proliferative activities similar
      to the analogous proteins from mammalian cells: furthermore, biophysical analysis
      indicated that the E19A mutation does not cause gross structural perturbations in
      G-CSF. Although G-CSF is likely to signal through receptor homo-dimerization, we
      found no compelling evidence for a second receptor binding region. We also found
      no evidence of self-antagonism at high G-CSF concentrations, suggesting that, in
      contrast to human growth hormone (hGH) and erythropoietin (EPO), G-CSF probably
      does not signal via a pure 2:1 receptor ligand complex. Thus, G-CSF, while having
      a similar tertiary structure to hGH and EPO, uses different areas of the four
      helix bundle for high-affinity interaction with its receptor.

PMID- 9194182
TI  - Refined structures of three crystal forms of toxic shock syndrome toxin-1 and of
      a tetramutant with reduced activity.
AB  - The structure of toxic shock syndrome toxin-1 (TSST-1), the causative agent in
      toxic shock syndrome, has been determined in three crystal forms. The three
      structural models have been refined to R-factors of 0.154, 0.150, and 0.198 at
      resolutions of 2.05 A, 2.90 A, and 2.75 A, respectively. One crystal form of TSST
      1 contains a zinc ion bound between two symmetry-related molecules. Although not
      required for biological activity, zinc dramatically potentiates the mitogenicity
      of TSST-1 at very low concentrations. In addition, the structure of the
      tetramutant TSST-1H [T69I, Y80W, E132K, I140T], which is nonmitogenic and does
      not amplify endotoxin shock, has been determined and refined in a fourth crystal
      form (R-factor = 0.173 to 1.9 A resolution).

PMID- 9194184
TI  - Secondary and tertiary structural changes in gamma delta resolvase: comparison of
      the wild-type enzyme, the I110R mutant, and the C-terminal DNA binding domain in
      solution.
AB  - gamma delta Resolvase is a site-specific DNA recombinase (M(r) 20.5 kDa) in
      Escherichia coli that shares homology with a family of bacterial resolvases and
      invertases. We have characterized the secondary and tertiary structural behavior
      of the cloned DNA binding domain (DBD) and a dimerization defective mutant in
      solution. Low-salt conditions were found to destabilize the tertiary structure of
      the DBD dramatically, with concomitant changes in the secondary structure that
      were localized near the hinge regions between the helices. The molten tertiary
      fold appears to contribute significantly to productive DNA interactions and
      supports a mechanism of DNA-induced folding of the tertiary structure, a process
      that enables the DBD to adapt in conformation for each of the three imperfect
      palindromic sites. At high salt concentrations, the monomeric I110R resolvase
      shows a minimal perturbation to the three helices of the DBD structure and
      changes in the linker segment in comparison to the cloned DBD containing the
      linker. Comparative analysis of the NMR spectra suggest that the I110R mutant
      contains a folded catalytic core of approximately 60 residues and that the
      segment from residues 100 to 149 are devoid of regular structure in the I110R
      resolvase. No increase in the helicity of the linker region of I110R resolvase
      occurs on binding DNA. These results support a subunit rotation model of strand
      exchange that involves the partial unfolding of the catalytic domains.

PMID- 9194185
TI  - Refined solution structure and backbone dynamics of HIV-1 Nef.
AB  - The tendency of HIV-1 Nef to form aggregates in solution, particularly at pH
      values below 8, together with its large fraction of highly mobile residues
      seriously complicated determination of its three-dimensional structure, both for
      heteronuclear solution NMR (Grzesiek et al., 1996a, Nat Struct Biol 3:340-345)
      and for X-ray crystallography (Lee et al., 1996, Cell 85:931-942). Methods used
      to determine the Nef structure by NMR at pH 8 and 0.6 mM concentration are
      presented, together with a detailed description of Nef's secondary and tertiary
      structure. The described techniques have general applicability for the NMR
      structure determination of proteins that are aggregating and/or have limited
      stability at low pH values. Extensive chemical shift assignments are reported for
      backbone and side chain 1H, 13C, and 15N resonances of the HIV-1 Nef deletion
      mutants NEF delta 2-39, NEF delta 2-39, delta 159-173, and of NEF delta 2-39,
      delta 159-173 in complex with the SH3 domain of the Hck tyrosine protein kinase.
      Besides a type II polyproline helix, Nef's structure consists of three alpha
      helices, a 3(10) helix, and a five-stranded anti-parallel beta-sheet. The
      analysis of 15N relaxation parameters of the backbone amide sites reveals that
      all the secondary structure elements are non-mobile on the picosecond to
      nanosecond and on the millisecond time scale. A large number of slowly exchanging
      amide protons provides evidence for the stability of the Nef core even on the
      time scale of hours. Significant internal motions on the ps to ns time scale are
      detected for residues 60 to 71 and for residues 149 to 180, which form solvent
      exposed loops. The residues of the HIV-1 protease cleavage site (W57/L58) do not
      exhibit large amplitude motions on the sub-nanosecond time scale, and their side
      chains insert themselves into a hydrophobic crevice formed between the C-terminus
      of helix 1 and the N-terminus of helix 2. A refined structure has been determined
      based on additional constraints for side-chain and backbone dihedral angles
      derived from a large number of three-bond J-coupling and ROE data.

PMID- 9194186
TI  - The role of context on alpha-helix stabilization: host-guest analysis in a mixed
      background peptide model.
AB  - The helix content of a series of peptides containing single substitutions of the
      20 natural amino acids in a new designed host sequence, succinyl
      YSEEEEKAKKAXAEEAEKKKK-NH2, has been determined using CD spectroscopy. This host
      is related to one previously studied, in which triple amino acid substitutions
      were introduced into a background of Glu-Lys blocks completely lacking alanine.
      The resulting free energies show that only Ala and Glu- prove to be helix
      stabilizing, while all other side chains are neutral or destabilizing. This
      agrees with results from studies of alanine-rich peptide modela, but not the
      previous Glu-Lys block oligomers in which Leu and Met also stabilize helix. The
      helix propensity scale derived from the previous block oligomers correlated well
      with the frequencies of occurrence of different side chains in helical sequences
      of proteins, whereas the values from the present series do not. The role of
      context in determining scales of helix propensity values is discussed, and the
      ability of algorithms designed to predict helix structure from sequence is
      compared.

PMID- 9194187
TI  - Design of a leucine zipper coiled coil stabilized 1.4 kcal mol-1 by
      phosphorylation of a serine in the e position.
AB  - Using a dimeric bZIP protein, we have designed a leucine zipper that becomes more
      stable after a serine in the e position is phosphorylated by protein kinase A
      (delta delta GP = -1.4 kcal mol-1 dimer-1 or -0.7 kcal mol-1 residue-1).
      Mutagenesis studies indicate that three arginines form a network of inter-helical
      (i,i' + 5; i, i' + 2) and intra-helical (i, i + 4) attractive interactions with
      the phosphorylated serine. When the arginines are replaced with lysines, the
      stabilizing effect of serine phosphorylation is reduced (delta delta GP = -0.5
      kcal mol-1 dimer-1). The hydrophobic interface of the leucine zipper needs a
      glycine in the d position to obtain an increase in stability after
      phosphorylation. The phosphorylated protein binds DNA with a 15-fold higher
      affinity. Using a transient transfection assay, we document a PKA dependent four
      fold activation of a reporter gene. Phosphorylation of a threonine in the same e
      position decreases the stability by delta delta GP = +1.2 kcal mol-1 dimer-1. We
      present circular dichroism (CD) thermal denaturations of 15 bZIP proteins before
      and after phosphorylation. These data provide insights into the structural
      determinants that result in stabilization of a coiled coil by phosphorylation.

PMID- 9194188
TI  - Mapping of the plasminogen binding site of streptokinase with short synthetic
      peptides.
AB  - Although several recent studies employing various truncated fragments of
      streptokinase (SK) have demonstrated that the high-affinity interactions of this
      protein with human plasminogen (HPG) to form activator complex (SK-HPG) are
      located in the central region of SK, the exact location and nature of such HPG
      interacting site(s) is still unclear. In order to locate the "core" HPG binding
      ability in SK, we focused on the primary structure of a tryptic fragment of SK
      derived from the central region (SK143-293) that could bind as well as activate
      HPG, albeit at reduced levels in comparison to the activity of the native, full
      length protein. Because this fragment was refractory to further controlled
      proteolysis, we took recourse to a synthetic peptide approach wherein the HPG
      interacting properties of 16 overlapping 20-mer peptides derived from this region
      of SK were examined systematically. Only four peptides from this set, viz., SK234
      253, SK254-273, SK274-293, and SK263-282, together representing the contiguous
      sequence SK234-293, displayed HPG binding ability. This was established by a
      specific HPG-binding ELISA as well as by dot blot assay using 125I-labeled HPG.
      These results showed that the minimal sequence with HPG binding function resided
      between residues 234 and 293. None of the synthetic SK peptides was found to
      activate HPG, either individually or in combination, but, in competition
      experiments where each of the peptides was added prior to complex formation
      between SK and HPG, three of the HPG binding peptides (SK234-253, SK254-273, and
      SK274-293) inhibited strongly the generation of a functional activator complex by
      SK and HPG. This indicated that residues 234-293 in SK participate directly in
      intermolecular contact formation with HPG during the formation of the 1:1 SK-HPG
      complex. Two of the three peptides (SK234-253 and SK274-293), apart from
      interfering in SK-HPG complex formation, also showed inhibition of the amidolytic
      activity of free HPN by increasing the K(m) by approximately fivefold. A similar
      increase in K(m) for amidolysis by HPN as a result of complexation with SK has
      been interpreted previously to arise from the steric hinderance at or near the
      active site due to the binding of SK in this region. Thus, our results suggest
      that SK234-253 and SK274-293 also, like SK, bound close to the active site of
      HPN, an event that was reflected in the observed alteration in its substrate
      accessibility. By contrast, whereas the intervening peptide (SK254-273) could not
      inhibit amidolysis by free HPN, it showed a marked inhibition of the activation
      of "substrate" PG (human or bovine plasminogen) by activator complex, indicating
      that this particular region is intimately involved in interaction of the SK-HPG
      activator complex with substrate plasminogen during the catalytic cycle. This
      finding provides a rational explanation for one of the most intriguing aspects of
      SK action, i.e., the ability of the SK-HPG complex to catalyze selectively the
      activation of substrate molecules of PG to PN, whereas free HPN alone cannot do
      so. Taken together, the results presented in this paper strongly support a model
      of SK action in which the segment 234-293 of SK, by virtue of the epitopes
      present in residues 234-253 and 274-293, binds close to the active center of HPN
      (or, a cryptic active site, in the case of HPG) during the intermolecular
      association of the two proteins to form the equimolar activator complex; the
      segment SK254-273 present in the center of the core region then imparts an
      ability to the activator complex to interact selectively with substrate PG
      molecules during each PG activation cycle.

PMID- 9194190
TI  - Hydrophobicity regained.
AB  - A widespread practice is to use free energies of transfer between organic
      solvents and water (delta G0transfer to define hydrophobicity scales for the
      amino acid side chains. A comparison of four delta G0transfer scales reveals that
      the values for hydrogen-bonding side chains are highly dependent on the non
      aqueous environment. This property of polar side chains violates the assumptions
      underlying the paradigm of equating delta G0transfer with hydrophobicity or even
      with a generic solvation energy that is directly relevant to protein stability
      and ligand binding energetics. This simple regaining of the original concept of
      hydrophobicity reveals a flaw in approaches that use delta G0transfer values to
      derive generic estimates of the energetics of the burial of polar groups, and
      allows the introduction of a "pure" hydrophobicity scale for the amino acid
      residues.

PMID- 9194189
TI  - On the calculation of binding free energies using continuum methods: application
      to MHC class I protein-peptide interactions.
AB  - This paper describes a methodology to calculate the binding free energy (delta G)
      of a protein-ligand complex using a continuum model of the solvent. A formal
      thermodynamic cycle is used to decompose the binding free energy into
      electrostatic and non-electrostatic contributions. In this cycle, the reactants
      are discharged in water, associated as purely nonpolar entities, and the final
      complex is then recharged. The total electrostatic free energies of the protein,
      the ligand, and the complex in water are calculated with the finite difference
      Poisson-Boltzmann (FDPB) method. The nonpolar (hydrophobic) binding free energy
      is calculated using a free energy-surface area relationship, with a single
      alkane/water surface tension coefficient (gamma aw). The loss in backbone and
      side-chain configurational entropy upon binding is estimated and added to the
      electrostatic and the nonpolar components of delta G. The methodology is applied
      to the binding of the murine MHC class I protein H-2Kb with three distinct
      peptides, and to the human MHC class I protein HLA-A2 in complex with five
      different peptides. Despite significant differences in the amino acid sequences
      of the different peptides, the experimental binding free energy differences
      (delta delta Gexp) are quite small (< 0.3 and < 2.7 kcal/mol for the H-2Kb and
      HLA-A2 complexes, respectively). For each protein, the calculations are
      successful in reproducing a fairly small range of values for delta delta Gcalc (<
      4.4 and < 5.2 kcal/mol, respectively) although the relative peptide binding
      affinities of H-2Kb and HLA-A2 are not reproduced. For all protein-peptide
      complexes that were treated, it was found that electrostatic interactions oppose
      binding whereas nonpolar interactions drive complex formation. The two types of
      interactions appear to be correlated in that larger nonpolar contributions to
      binding are generally opposed by increased electrostatic contributions favoring
      dissociation. The factors that drive the binding of peptides to MHC proteins are
      discussed in light of our results.

PMID- 9194191
TI  - Determination of the disulfide bond arrangement of human respiratory syncytial
      virus attachment (G) protein by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry.
AB  - The attachment protein or G protein of the A2 strain of human respiratory
      syncytial virus (RSV) was digested with trypsin and the resultant peptides
      separated by reverse-phase high-performance liquid chromatography (HPLC). One
      tryptic peptide produced a mass by matrix-assisted laser desorption/ionization
      (MALDI) time-of-flight (TOF) mass spectrometry (MS) corresponding to residues 152
      187 with the four Cys residues of the ectodomain (residues 173, 176, 182, and
      186) in disulfide linkage and absence of glycosylation. Sub-digestion of this
      tryptic peptide with pepsin and thermolysin produced peptides consistent with
      disulfide bonds between Cys173 and Cys186 and between Cys176 and Cys182. Analysis
      of ions produced by post-source decay of a peptic peptide during MALDI-TOF-MS
      revealed fragmentation of peptide bonds with minimal fission of an inter-chain
      disulfide bond. Ions produced by this unprecedented MALDI-induced post-source
      fragmentation corroborated the existence of the disulfide arrangement deduced
      from mass analysis of proteolysis products. These findings indicate that the
      ectodomain of the G protein has a non-glycosylated subdomain containing a
      "cystine noose."

PMID- 9194192
TI  - Hydrogen exchange properties of proteins in native and denatured states monitored
      by mass spectrometry and NMR.
AB  - The extent of deuterium labeling of hen lysozyme, its three-disulfide derivative,
      and the homologous alpha-lactalbumins, has been measured by both mass
      spectrometry and NMR. Different conformational states of the proteins were
      produced by varying the solution conditions. Alternate protein conformers were
      found to contain different numbers of 2H atoms. Furthermore, measurement in the
      gas phase of the mass spectrometer or directly in solution by NMR gave consistent
      results. The unique ability of mass spectrometry to distinguish distributions of
      2H atoms in protein molecules is exemplified using samples prepared to contain
      different populations of 2H-labeled protein. A comparison of the peak widths of
      bovine alpha-lactalbumin in alternate solution conformations but containing the
      same average number of 2H atoms showed dramatic differences due to different 2H
      distributions in the two protein conformers. Measurement of 2H distributions by
      ESI-MS enabled characterization of conformational averaging and structural
      heterogeneity. In addition, a time course for hydrogen exchange was examined and
      the variation in distributions of 2H atom compared with simulations for different
      hydrogen exchange models. The results clearly show that exchange from the native
      state of bovine alpha-lactalbumin at 15 degrees C is dominated by local unfolding
      events.

PMID- 9194194
TI  - Automated design of the surface positions of protein helices.
AB  - Using a protein design algorithm that quantitatively considers side-chain
      interactions, the design of surface residues of alpha helices was examined. Three
      scoring functions were tested: a hydrogen-bond potential, a hydrogen-bond
      potential in conjunction with a penalty for uncompensated burial of polar
      hydrogens, and a hydrogen-bond potential in combination with helix propensity.
      The solvent exposed residues of a homodimeric coiled coil based on GCN4-p1 were
      designed by using the Dead-End Elimination Theorem to find the optimal amino acid
      sequence for each scoring function. The corresponding peptides were synthesized
      and characterized by circular dichroism spectroscopy and size exclusion
      chromatography. The designed peptides were dimeric and nearly 100% helical at 1
      degree C, with melting temperatures from 69-72 degrees C, over 12 degrees C
      higher than GCN4-p1, whereas a random hydrophilic sequence at the surface
      positions produced a peptide that melted at 15 degrees C. Analysis of the
      designed sequences suggests that helix propensity is the key factor in sequence
      design for surface helical positions.

PMID- 9194193
TI  - The adaptability of Escherichia coli thioredoxin to non-conservative amino acid
      substitutions.
AB  - The adaptability of Escherichia coli thioredoxin to the substitution of a series
      of non-natural amino acids has been investigated. Different thiosulfonated alkyl
      groups were inserted into the hydrophobic core of the protein in position 78 via
      disulfide bonding with a buried cysteine residue as previously described (Wynn R,
      Richards FM. 1993. Unnatural amino acid packing mutants of Escherichia coli
      thioredoxin produced by combined mutagenesis/chemical modification techniques.
      Protein Sci 2:395-403). The side chains added to the cysteine included methyl,
      ethyl, n-propyl, n-butyl, n-pentyl, and cyclo-pentyl derivatives. The side chains
      appear to exploit the presence of the large cavities to incorporate these variant
      forms, enabling the protein to fold and have some activity. Solution structural
      and kinetic data suggested that these substitutions had little effect on the
      overall fold of the protein. Thermodynamic data revealed that the entropic effect
      of restricting the side chains in the folded protein has an effect on the
      stability. The variant forms of thioredoxin have different propensities to form
      dimers despite the limited structural perturbations. Molecular modeling studies
      allow the conformation of the side chains to be assessed.

PMID- 9194195
TI  - Crystallographic analysis of the pH-dependent binding of iminobiotin by
      streptavidin.
AB  - Streptavidin binds 2'-iminobiotin in a pH-dependent fashion--affinity decreases
      as the pH is lowered. This property makes the purification of compounds
      conjugated to streptavidin or immobiotin possible under mild conditions by
      affinity chromatography. In order to understand the molecular details of this pH
      dependent binding, we analyzed the crystal structures of the complex of core
      streptavidin with 2'-iminobiotin at pH values 4.0 and 7.5. The two structures are
      very similar to each other even at their binding sites. Although the relative
      abundance of the protonated species of the ligand is increased more than 3,000
      fold on going from pH 7.5 to pH 4.0, both structures contain only the
      nonprotonated from of the ligand. Streptavidin selects the nonprotonated form,
      which, at pH 4.0, is one part in 7.9 x 10(7).

PMID- 9194196
TI  - Characterization and crystallization of human uroporphyrinogen decarboxylase.
AB  - The cytosolic enzyme uroporphyrinogen decarboxylase (URO-D) catalyzes the fifth
      step in the heme biosynthetic pathway, converting uroporphyrinogen to
      coproporphyrinogen by decarboxylating the four acetate side chains of the
      substrate. Recombinant human URO-D has been expressed in Escherichia coli with a
      histidine tag and has been purified to homogeneity. Purified protein was
      determined to be a monodisperse dimer by dynamic light scattering. Equilibrium
      sedimentation analysis confirmed that the protein is dimeric, with a dissociation
      constant of 0.1 microM. URO-D containing an amino-terminal histidine tag was
      crystallized in space group P3(1)21 or its enantiomer P3(2)21 with unit cell
      dimensions a = b = 103.6 A, c = 75.2 A. There is one molecule in the asymmetric
      unit, consistent with generation of the dimer by the twofold axis of this
      crystallographic operator. Native data have been collected to 3.0 a resolution.

PMID- 9194197
TI  - Nuclear magnetic resonance assignment and secondary structure of an ankyrin-like
      repeat-bearing protein: myotrophin.
AB  - Multidimensional heteronuclear NMR has been applied to the structural analysis of
      myotrophin, a novel protein identified from spontaneously hypertensive rat hearts
      and hypertrophic human hearts. Myotrophin has been shown to stimulate protein
      synthesis in myocytes and likely plays an important role in the initiation of
      cardiac hypertrophy, a major cause of mortality in humans. Recent cDNA cloning
      revealed that myotrophin has 11B amino acids containing 2.5 contiguous ANK
      repeats, a motif known to be involved in a wide range of macromolecular
      recognition. A series of two- and three-dimensional heteronuclear bond
      correlation NMR experiments have been performed on uniformly 15N-labeled or
      uniformly 15N/13C-labeled protein to obtain the 1H, 15N, and 13C chemical shift
      assignments. The secondary structure of myotrophin has been determined by a
      combination of NOEs, NH exchange data, 3JHN alpha coupling constants, and
      chemical shifts of 1H alpha, 13C alpha, and 13 C beta. The protein has been found
      to consist of seven helices, all connected by turns or loops. Six of the seven
      helices (all but the C-terminal helix) form three separate helix-turn-helix
      motifs. The two full ANK repeats in myotrophin are characteristic of multiple
      turns followed by a helix-turn-helix motif. A hairpin-like turn involving L32-R36
      in ANK repeat #1 exhibits slow conformational averaging on the NMR time scale and
      appears dynamically different from the corresponding region (D65-169) of ANK
      repeat #2.

PMID- 9194199
TI  - How protein chemists learned about the hydrophobic factor.
AB  - It is generally accepted today that the hydrophobic force is the dominant
      energetic factor that leads to the folding of polypeptide chains into compact
      globular entities. This principle was first explicitly introduced to protein
      chemists in 1938 by Irving Langmuir, past master in the application of
      hydrophobicity to other problems, and was enthusiastically endorsed by J.D.
      Bernal. But both proposal and endorsement came in the course of a debate about a
      quite different structural principle, the so-called "cyclol hypothesis" proposed
      by D. Wrinch, which soon proved to be theoretically and experimentally
      unsupportable. Being a more tangible idea, directly expressed in structural
      terms, the cyclol hypothesis received more attention than the hydrophobic
      principle and the latter never actually entered the mainstream of protein science
      until 1959, when it was thrust into the limelight in a lucid review by W.
      Kauzmann. A theoretical paper by H.S. Frank and M. Evans, not itself related to
      protein folding, probably played a major role in the acceptance of the
      hydrophobicity concept by protein chemists because it provided a crude but
      tangible picture of the origin of hydrophobicity per se in terms of water
      structure.

PMID- 9194198
TI  - Regulation and crystallization of phosphorylated and dephosphorylated forms of
      truncated dimeric phenylalanine hydroxylase.
AB  - Phenylalanine hydroxylase is regulated in a complex manner, including activation
      by phosphorylation. It is normally found as an equilibrium of dimeric and
      tetrameric species, with the tetramer thought to be the active form. We converted
      the protein to the dimeric form by deleting the C-terminal 24 residues and show
      that the truncated protein remains active and regulated by phosphorylation. This
      indicates that changes in the tetrameric quaternary structure of phenylalanine
      hydroxylase are not required for enzyme activation. Truncation also facilitates
      crystallization of both phosphorylated and dephosphorylated forms of the enzyme.

PMID- 9194200
TI  - No association between bipolar affective disorder and a serotonin receptor (5
      HT2A) polymorphism.
AB  - The serotonergic system is implicated in the pathogenesis of affective disorders.
      In particular, the role of the postsynaptic 5-hydroxytryptamine (serotonin) type
      2 receptor (5-HT2) has been documented by several studies. The 5-HT2A receptor
      gene located on chromosome 13 (13q14-21) can be considered a candidate gene for
      bipolar affective disorder (BPAD). We tested association between a 5-HT2A
      receptor DNA variant and BPAD using a case-control design. Eighty-three BPAD
      patients and 129 unrelated normal controls, carefully matched for sex and
      geographical origin, were studied. Allele and genotype frequencies as well as
      homo-heterozygote distribution at the 5-HT2A receptor polymorphism were compared
      between the two groups. No significant allelic or genotypic associations were
      observed. There was no significant difference for homo-heterozygote distribution
      between the two groups. These preliminary results may indicate that in our sample
      the 5-HT2 receptor polymorphism studied is unlikely to play a role in the genetic
      susceptibility to BPAD.

PMID- 9194201
TI  - Effects of P50 temporal variability on sensory gating in schizophrenia.
AB  - The conditioning-testing (S1-S2) P50 auditory evoked potential (EP) has been well
      documented and accepted as an important tool for measuring sensory gating in
      schizophrenia research. However, the physiological mechanism of the phenomenon is
      not known. In this study a single-trial analysis was used to determine the
      influence of the latency variability of the responses in the formation of the
      averaged P50. Ten schizophrenic patients and 10 normal controls were tested in
      the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the
      previous finding of a lower S1 P50 amplitude and higher S2/S1 ratio in
      schizophrenics compared with normal controls. The single-trial analysis revealed
      that patients had significantly higher trial-to-trial latency variability in S1
      responses than normal subjects, while the S2 showed the same variability as in
      controls. Measured by the single-trial procedure, the arithmetic mean amplitudes
      of P50 responses to S1 and S2 were similar between normal and schizophrenic
      subjects. The same measure also eliminated the difference in averaged P50
      amplitude between S1 and S2 for both groups. Temporal variability appears to be
      an important factor in the assessment of averaged EPs and thus contribute to the
      change of P50 amplitude observed in schizophrenia.

PMID- 9194202
TI  - Relationship between the five-factor model of personality and unipolar, bipolar
      and schizophrenic patients.
AB  - The purpose of this study was to examine personality differences among three
      different Axis I disorders-recovered patients with unipolar depression (n = 62),
      euthymic patients with bipolar disorder (n = 34), and patients with schizophrenia
      in the residual phase of their illness (n = 41) using the five-factor model of
      personality (FFM). The dimensions of the FFM-Neuroticism (N), Extraversion (E),
      Openness (O), Agreeableness (A), and Conscientiousness (C)-were measured with
      composite scores derived from the NEO Personality Inventory (NEO PI) and the
      Revised NEO Personality Inventory (NEO PI-R). While no group differences emerged
      on N or C, the bipolar patients scored significantly higher on the Positive
      Emotion facet (subscale) of E than the unipolar patients. The schizophrenic
      patients scored lower on the Feelings, Values and Actions facets of O than did
      the unipolar and bipolar patients. The unipolar patients scored higher on A than
      the schizophrenic patients.

PMID- 9194203
TI  - Discrimination and response bias in memory: effects of depression severity and
      psychomotor retardation.
AB  - Although memory disorders have been well documented in depression, there is
      controversy concerning depressives' performance on recognition memory tasks; e.g.
      whether they have impaired discrimination and conservative or liberal response
      bias according to signal detection theory. In addition, symptomatic correlates of
      discrimination and response bias indices have been lacking. A word recognition
      memory task analyzed according to the two high threshold theory was administered
      to 26 depressives and 26 controls. Depressives obtained a lower index of
      discrimination (Pr) than controls. The index of response bias (Br) was not
      different between groups. In the depressed group, overall severity of depression
      was related to discrimination, whereas psychomotor retardation level was related
      to response bias. Cognitive performance of depressives could be advantageously
      analyzed in terms of these two dimensions of symptomatology.

PMID- 9194204
TI  - Characteristics of obsessive-compulsive symptoms in Tourette's syndrome,
      obsessive-compulsive disorder, and Parkinson's disease.
AB  - A high incidence of obsessions and compulsions is documented in basal ganglia
      disorders, especially in patients with Tourette's syndrome (TS). A comparison of
      patients with obsessive-compulsive disorder (OCD), TS, and Parkinson's disease
      (PD) revealed significantly higher total scores in both OCD and TS patients than
      in a healthy control group on the Maudsley obsessive-compulsive inventory (MOCI)
      and the Hamburg obsessive-compulsive inventory (HZI-K), two self-report measures
      of obsessive-compulsive symptoms. On most subscales (especially Checking,
      Ordering, and Counting/touching), TS patients scored higher than controls.
      Patients with Parkinson's disease merely scored higher on the subscale 'Ordering'
      of the HZI-K. Differences between OCD patients and TS patients were evident on
      the MOCI subscales 'Checking' and 'Slowness/Repetition' as well as on the MOCI
      total score and on the HZI subscales 'Cleaning' and 'Obsessive Thoughts'. On
      these scales, TS patients reported fewer symptoms than OCD patients. Stepwise
      discriminant analysis with preselected single items as variables was used to look
      for specific symptom patterns of OCD and TS. Seventy-eight percent of the
      patients could be correctly classified with respect to their diagnoses on the
      basis of only two items of the HZI-K. One item asks for fearful obsessive
      thoughts, which was found in 90% of the OCD patients; the second item represented
      echo phenomena, found in 56% of the TS patients. It is concluded that considering
      specific patterns of obsessive-compulsive psychopathology may contribute to a
      more reliable differential diagnosis in OCD and TS and help to avoid misdiagnosis
      of OCD in TS patients.

PMID- 9194205
TI  - Numbing scale scores in female psychiatric inpatients diagnosed with self
      injurious behavior, dissociative identity disorder, and major depression.
AB  - Female inpatients engaged in self-injurious behavior (SIB) and females diagnosed
      with Dissociative Identify Disorder (DID) scored higher on the Glover Numbing
      Scale (GNS) than female inpatients diagnosed with Major Depressive Disorder
      (MDD). The DID sample showed a multi-modal distribution of scores, and the MDD
      sample showed a bimodal distribution with a significant difference between the
      means of the two subgroups. An additional subsample of outpatient males diagnosed
      with MDD also evidenced a bimodal distribution of scores with a similar spread
      between the two means. Scores on the Beck Depression Inventory did not
      discriminate the latter two subgroups.

PMID- 9194206
TI  - Reduction of hyponatremia in a schizophrenic with polydipsia-hyponatremia
      syndrome by surgical intervention.
AB  - In a chronic schizophrenic with polydipsia-hyponatremia syndrome, we observed
      physiological data consecutively before and after a successful LAPIDES
      vesicostomy for his bladder retention. Although his polydipsia was unchanged,
      frequency of hyponatremia was significantly reduced after the operation. We found
      that bladder retention might be one of the factors relevant to the prediction of
      hyponatremia from diurnal weight gain.

PMID- 9194207
TI  - The frequency of autoantibodies in Turkish patients with lupus nephritis.
AB  - We analysed the frequency of autoantibodies in 44 patients with lupus nephritis.
      Antinuclear antibody (ANA) was found in 91% of patients by an indirect
      immunofluorescence technique on HEp-2 cells at the time of study. Anti-dsDNA
      antibodies were found at high levels in most of the patients using the SynELISA
      test, which reveals both high and low avidity antibodies, but only in 64% of
      patients using the DAKO assay, which reveals high avidity antibodies. Anti
      histone antibodies were found in 52% of the patients. Anti-SSA/Ro antibodies were
      positive in 27% of all patients; these patients also had prominent cutaneous
      involvement and photosensitivity. The frequency of anti-SSB/La and Anti-Sm
      antibodies was 7%. Immunoblotting experiments confirmed the findings shown by the
      techniques described above, and anti-ribosomal antibodies were found to be
      positive in more cases by the latter assay. IgA rheumatoid factor (RF) was more
      frequent (20.4%) than IgM RF (9.9%). In conclusion, Turkish patients suffering
      from lupus nephritis seem to express a total autoantibody profile similar to that
      reported for systemic lupus erythematosus from other parts of Europe.

PMID- 9194208
TI  - A comparison between bucillamine and D-penicillamine in the treatment of
      rheumatoid arthritis.
AB  - In order to compare the clinical effect and the frequency of side effect of D
      penicillamine and bucillamine, we conducted a randomized, controlled clinical
      trial. Twenty-two and 24 patients were allocated to each section of the study,
      respectively. Bucillamine was at least as effective ad D-penicillamine in terms
      of improvement in the swollen joint count, tenderness score, morning stiffness,
      modified health assessment questionnaire, and Westergren erythrocyte
      sedimentation rate (ESR), and more effective in terms of improvement in the
      tender joint count, grip strength, C-reactive protein (CRP), and rheumatoid
      factor (RF) titer. In all, 27% of the bucillamine group and 33% of the D
      penicillamine group responded; the response rate did not differ significantly
      between the two groups. The frequency of side effects tended to be lower in the
      bucillamine group. In conclusion, bucillamine was as effective as D-penicillamine
      in the treatment of rheumatoid arthritis, and with the former the frequency of
      side effects tended to be lower.

PMID- 9194209
TI  - Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid
      arthritis, Crohn's disease and ulcerative colitis.
AB  - Specific immunoreactive anti-Klebsiella antibodies are found in patients with
      ankylosing spondylitis (AS), a significant proportion of whom have occult
      inflammatory bowel disease. Molecular mimicry between Klebsiella or other
      bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The
      specificity of increased immunoreactivity against Klebsiella remains to be
      assessed against the abundant anaerobic bacterial flora, present either in
      healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease
      (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by
      ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten
      anaerobic isolates of the predominant normal bowel flora in 35 patients with
      active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60
      patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig
      immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001),
      CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy
      controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly
      elevated only in RA patients, compared with the other inflammatory groups (P <
      0.001) and controls (P < 0.001). There was no significant antibody response
      against E. coli or the ten obligate anaerobes in any of the test groups. The data
      suggested an increased immune response to Klebsiella in patients with AS, UC, CD
      and to Proteus in patients with RA. The specificity of these responses in some
      patients supported a possible role for enteric Klebsiella in the pathogenesis of
      AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease
      requires further study.

PMID- 9194210
TI  - Endothelial cells are the major source of sICAM-1 in rheumatoid synovial tissue.
AB  - The objective of this research was to investigate the cellular source of soluble
      ICAM-1 (siCAM-1) from rheumatoid synovial tissue (RS) and its relation to sICAM-1
      in synovial fluid (SF) and serum, and to study the expression of ICAM-1 in
      isolated cells of RS. sICAM-1 was determined by using the enzyme-linked
      immunosorbent assay (ELISA) and Western blot analysis in supernatants from RS
      cultured for short periods (n = 19), in SF (n = 7) and in serum (n = 19). ICAM-1
      expression, vascularization and inflammatory infiltration (CD3, CD68, CD22) were
      characterized immunohistochemically in cytospin preparations (n = 18),
      cryosections (n = 18) and in conventionally stained paraffin sections (n = 19) of
      RS. The degree of RS vascularization was analysed morphometrically in
      immunohistochemically stained cryosections (factor VIII related antigen). We
      found 90-kD sICAM-1 in supernatants of cultured cells, in SF and in sera. sICAM-1
      in cellular supernatant correlated significantly (P < 0.01) with SF sICAM-1. The
      amount of sICAM in cellular supernatants showed no correlation to the score of
      inflammatory infiltration, but correlated significantly (P < 0.001) with the
      vascularization index of RS. The percentage of ICAM-1-expressing cells correlated
      significantly (P < 0.001) with the percentage of CD68-positive macrophages, but
      not with CD3- and CD22-positive lymphocytes. Macrophages, multinucleated giant
      cells and endothelial cells exhibited a higher expression of ICAM-1 as compared
      to lymphocytes and fibroblasts. The differential expression of ICAM-1 on
      infiltrating leucocytes and resident cells of RS indicates a functional role of
      ICAM-1 in the local inflammatory process. SF sICAM-1 originated in RS, but serum
      sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory
      infiltration, but depended on the degree of vascularization, indicating that
      endothelial cells are the major source of sICAM-1 in RS.

PMID- 9194211
TI  - Elevated levels of insulin-like growth factor (IGF) binding protein-3 in
      rheumatoid arthritis synovial fluid inhibit stimulation by IGF-I of articular
      chondrocyte proteoglycan synthesis.
AB  - The objective of this study was to quantify insulin-like growth factor (IGF)
      binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with
      rheumatic diseases and to study the role of these proteins in the regulation of
      cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2,
      IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor
      alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with
      rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other
      rheumatic disorders. We also determined the effects of SF on bovine cartilage PG
      synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and
      28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA
      compared to age- and sex-matched OA controls (determined by RIA and confirmed by
      Western ligand blot). IGF-I and IGF-II did not differ significantly between the
      two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG
      synthesis in culture, and more than 60% of this activity was neutralised by a
      specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited
      the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA
      patients, the SF concentration of IGFBP-3 was positively correlated with SF
      levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein
      and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under
      the conditions studied, the most important anabolic factor in human SF with
      respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints
      is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated
      IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes,
      thus interfering with cartilage PG synthesis in RA.

PMID- 9194212
TI  - Coronary anomaly in Behcet's syndrome.
AB  - A 39-year-old man who was known to have Behcet's syndrome suffered an acute
      posterior-wall myocardial infarction. The infarction occurred 13 years after the
      onset of the Behcet's disease, which had been marked by recurrent chorioretinitis
      and thrombosis of the retinal veins of both eyes. Coronary arteriography showed
      occlusion of the circumflex branch and an aneurysmal fistula between the left
      main branch and the pulmonary artery. The other coronary vessels were normal. A
      search for vascular risk factors revealed only cigarette smoking. Under a non
      invasive treatment regimen, no complications of the mycoardial infarction were
      seen. During a 2-year medical follow-up, the patient was asymptomatic and did not
      show any further signs of Behcet's disease activity.

PMID- 9194213
TI  - Self-rating Barthel index compatible with the original Barthel index and the
      Functional Independence Measure motor score.
AB  - To confirm concurrent validity of the final revision of the self-rating Barthel
      index (SB) and its test-retest reliability, we investigated 171 stroke
      outpatients without severe aphasia or dementia who were seen by a doctor on
      predetermined days at eight different hospitals. For 41 patients, the differences
      in scores among the original Barthel index (BI) and Granger's BI and SB were
      examined by the Friedman two-way analysis of variance and Wilcoxon matched-pairs
      signed-ranks test, and the difference in scores between Functional Independence
      Measure motor score (FIM-MS) and three-level scale FIM-MS was determined by the
      Wilcoxon's matched-pairs signed-ranks test. Concurrent validity of the SB was
      confirmed by Spearman's correlation coefficients with the original BI and FIM-MS,
      and internal consistency of the five measuring instruments was examined. For all
      171 patients test-retest reliability of the SB was examined with the Spearman's
      correlation coefficient for total scores and kappa coefficients for each ADL
      item. Regression analysis was performed to determine what factors were related
      with test-retest reliability. Total scores of the SB and Granger's BI and the
      three-level scale FIM-MS were significantly higher than those of the original BI
      and FIM-MS, respectively. Correlation coefficients of the SB with the original BI
      and FIM-MS were 0.994 and 0.904, respectively, and its alpha-coefficient was
      0.842. Test-retest reliability of the total score was 0.835 by the correlation
      coefficient, and kappa coefficients of 1 and 12 ADL items were fair and good,
      respectively. Regression analysis revealed that self-rating by a patient with a
      high SB total score is more accurate. Therefore, the SB has good concurrent
      validity and is well-related with the original BI and FIM, and its test-retest
      reliability is sufficiently high for practical use.

PMID- 9194214
TI  - Influence of donor age on the cytotoxicity and mutagenicity of ethylnitrosourea
      in cultured human T-lymphocytes.
AB  - The effects of age on the cytotoxicity and mutagenicity of N-ethyl-N-nitrosourea
      (ENU) in human peripheral blood T-lymphocytes were investigated using colony
      forming assay in vitro. ENU was shown to induce a dose-dependent increase in cell
      killing and in mutation frequencies (MF). No significant correlation between age
      and ENU-induced 6-thioguanine-resistant (TGr) MF at the hypoxanthine
      phosphoribosyl transferase (HPRT) locus of the X-chromosome was found after
      treatment with the same concentration of ENU (1 mM or 2 mM). There were also no
      significant differences among different donor age groups and the sensitivity
      parameters for exposure to ENU. As X-rays, the cytotoxic and mutagenic effects of
      ENU in cultured human T-lymphocytes appear not to be associated with age. These
      results suggest that the repair of mutagen-induced DNA lesions does not decline
      with age. Such knowledge has implications for risk assessment and protection
      against environmental mutagens.

PMID- 9194215
TI  - [The clinicopathological features and operative results in a cancer of the
      remnant stomach--risk and prevention of cancer after partial gastrectomy].
AB  - The clinicopathological features and operative results were analyzed in 21
      patients undergoing an operation for cancer of the remnant stomach between 1979
      and 1997. The twenty-one patients were divided into two groups: Group A; n = 9:
      who had undergone a gastrectomy for benign gastric disease, Group B; n = 12: who
      had undergone the same operation for gastric cancer. In Group A, the interval
      between the first gastrectomy and the second was longer than in Group B. In both
      groups, a large number of advanced cancers (n = 16, 76.2%) and undifferentiated
      carcinomas (n = 15, 71.4%) were seen. Five-year-survival rates in Group A and
      Group B were 23.7%, 19.0%, respectively. The incidence of gastric stump cancer
      following partial gastrectomy was 80% in the patients on whom Billroth II
      reconstruction had been performed after gastrectomy. It is suggested that the
      residual stomach in the Billroth II reconstruction patients is susceptible to
      cancer development. Consideration of the reconstruction method and a systemic
      follow-up is needed to improve a prognosis.

PMID- 9194216
TI  - [The quality of bone].
AB  - The major determinant factors for the mechanical property of bone include the
      mass, structure and "quality" of bone. The quality indicates the factors which
      affect the strength of bone other than the mass and the structure. In the spinal
      cancellous bone, the power-law relationship has been observed and the bone
      strength increases in proportion to the square (the power number 2) of the bone
      mass value. The power number represents the quality of cancellous bone, including
      various factors such as the micro-structure at the tissue level and the physico
      chemical bonding at the molecular level. For the long cortical bone, the number
      or density of the cracks in the tissue represents the quality. The cortical bone
      strength decreases exponentially with the increase in the number of cracks in the
      tissue. The increase in the number of cracks with age is observed in the human
      skeleton. When a crack is made in the bone, the osteoclasts invade the region,
      refreshing the damaged tissue. Then, the osteoblasts are recruited to appose the
      new bone tissue, filling the gap made by the crack. Thus, the "quality" of bone
      is regulated by the bone cell functions as well as by the mass and the structure.
      Therefore, the regulation of the bone quality is another important target for
      bone cell biology.

PMID- 9194217
TI  - [A report on the present situation of primary care in USA and Canada].

PMID- 9194218
TI  - CTL effector functions.

PMID- 9194219
TI  - Functions of CD8 T-cell subsets secreting different cytokine patterns.
AB  - CD8+ T cells can differentiate into two effector phenotypes, Tc1 and Tc2,
      secreting different cytokine patterns. Both subsets are cytotoxic via the
      perforin and Fas pathways, and both kill resting and activated B cells, ruling
      out the possibility of cognate help, although Tc2 cells may provide bystander
      help. Both subsets induce inflammation with similar cellular infiltrates. Tc1
      cytokine synthesis is limited by two mechanisms--IL-4 induces a permanent
      deficiency in cytokine secretion, and rapid killing of target cells limits CD8+ T
      cell activation and cytokine production. These multiple CD8 T-cell activities
      provide a versatile set of immune functions.

PMID- 9194220
TI  - Fas and other cell death signaling pathways.
AB  - The Fas system ensures, within the immune system, one of the two main pathways of
      T-cell mediated cytotoxicity, and, importantly, at least part of the
      downregulation of immune responses. Recently, Fas has been increasingly
      implicated in other functions, such as protection of immune privileged tissues
      and disposal of cells undergoing genomic alterations. The Fas system can be
      viewed as a cell death signal, linking extracellular information to the cell
      death execution stage. In this review, the Fas pathway will be described,
      compared to the other known T-cell mediated cytotoxicity mechanism, and then more
      generally to other cell death signals. The general features of cell death
      signaling will be emphasized as well as the peculiarities of the Fas system.

PMID- 9194221
TI  - Protein sorting and secretion during CTL killing.
AB  - Now that the key proteins involved in target cell destruction during the lethal
      hit from CTL have been identified, an understanding of the mechanisms which
      regulate their delivery becomes important for understanding their relative
      contributions during CTL killing. This review summarizes what is known about the
      packaging and delivery of the different effector proteins involved in target cell
      destruction. The mechanisms which regulate their delivery during killing
      contribute to some of the unusual features of CTL killing, and give some clues
      about the different contributions in target cell destruction.

PMID- 9194222
TI  - Granulysin, a new human cytolytic granule-associated protein with possible
      involvement in cell-mediated cytotoxicity.
AB  - A primary process by which cytotoxic T lymphocytes (CTL) and natural killer (NK)
      cells lyse target cells involves the regulated exocytosis of granules present in
      the cytoplasm of the effector. These granules contain proteins, such as perforin
      and the granzymes, that play a direct role in the killing process. The
      localization of a human T and NK cell-specific protein, granulysin (formerly
      519), to cytolytic granules suggests that additional mechanisms may be involved
      in granule-mediated cytolysis. This protein shares homology with small, granule
      associated molecules and is a member of a larger family of proteins known as
      saposin-like proteins (SAPLIP). SAPLIP share common structural features allowing
      for association with lipids while retaining the ability to mediate a variety of
      different functions. Expression of granulysin is induced late after T-cell
      activation, similar to perforin and the granzymes. Two prominent protein products
      of 15 and 9kDa were identified in CTL. The 9kDa form localizes to dense, highly
      cytolytic granules and contains the SAPLIP homology domain. A recombinant
      granulysin protein, corresponding to the 9kDa form, is cytolytic against tumor
      cell targets.

PMID- 9194223
TI  - The role of granzyme B cluster proteases in cell-mediated cytotoxicity.
AB  - Granzymes are neutral serine proteases that are stored in the specialized lytic
      granules of cytotoxic lymphocytes. A mutation introduced into the granzyme B
      locus leads to a severe defect in the ability of cytotoxic lymphocytes to induce
      apoptosis in susceptible target cells, and reduces the severity of class I
      dependent acute graft-versus-host disease (GvHD). However, granzyme B-independent
      cytotoxicity also exists: in CD8+ cells, most of it is perforin-dependent, but in
      CD4+ cells, the Fas system and an additional pathway are involved. The
      identification of these pathways and their physiological relevance may lead to
      new approaches for inhibiting cytotoxic lymphocyte functions.

PMID- 9194224
TI  - Do CTL kill target cells by inducing apoptosis?
AB  - Inhibitors of ICE-family proteases (caspases) block many examples of apoptotic
      cell death in vivo and in vitro, including multiple apoptotic stimuli for T
      lymphocytes. We have tested whether cell death induced by cytotoxic T lymphocytes
      was also blocked by caspase inhibitors. We found that the rapid apoptotic target
      cell death induced by Fas ligand-bearing CTL using the target Fas death pathway
      was efficiently blocked by caspase inhibitors. In contrast, target lysis induced
      by the CTL granule exocytosis pathway is not detectably blocked by such
      inhibitors, although the accompanying apoptotic nuclear damage is efficiently
      blocked. Thus caspase inhibitors prevent the hallmark phenotype of apoptosis
      without measurably affecting target cell death as evidenced by lysis.

PMID- 9194226
TI  - Observer variation in the detection of acetabular bone deficiencies.
AB  - To determine observer variation in the detection of acetabular bone deficiencies,
      42 pairs of frontal (AP) and lateral hip radiographs and CT studies for total hip
      arthroplasty patients obtained within an average of 4 weeks of each other were
      reviewed separately by five radiologists and one orthopedic surgeon.
      Interobserver variations were calculated for each individual reading the films
      using kappa values. The individual film readings were then compared with a
      consensus reading of the CT data. When separate observers were analyzed,
      agreement on plain film readings was slight to fair (av. kappa = 0.1440 +/-
      0.1047). The individual observers were not able to give readings which were very
      consistent with the CT consensus reading, resulting in a low sensitivity (65%)
      and specificity (74%) for acetabular defect classification with plain
      radiographs. The identification of acetabular bone defects from the AP and
      lateral views of the hip is highly subjective and variable from observer to
      observer.

PMID- 9194225
TI  - The scapholunate interosseous ligament in MR arthrography of the wrist:
      correlation with non-enhanced MRI and wrist arthroscopy.
AB  - OBJECTIVE: To compare three-compartment MR wrist arthrography with non-enhanced
      MRI in correlation with wrist arthroscopy, and to evaluate the potential of MR
      arthrography for consistently visualizing all parts of the scapholunate
      interosseous ligament of the wrist (SLIL) and exactly diagnosing the site and
      extent of SLIL defects. DESIGN AND PATIENTS: In 41 patients with wrist pain (34
      patients with wrist pain for more than 6 months) plain radiographs, stress views,
      non-enhanced MRI and three-compartment MR arthrography were done within 2 h of
      each other, using three-dimensional volume acquisition (0.6-1.0 mm effective
      slice thickness) with a gradient-recalled echo sequence and a 1.5-T magnet. The
      MR arthrography findings were compared with the findings from non-enhanced MRI
      and correlated with the arthroscopic findings in all patients. RESULTS: The
      dorsal, central and palmar segments of the SLIL could be delineated exactly by MR
      arthrography in 95% of the patients; with non-enhanced MRI only 28% of SLIL
      segments were seen consistently. Demonstration of SLIL defects was possible with
      high diagnostic confidence in 42% of SLIL segments by non-enhanced MRI and in 94%
      by MR arthrography. With wrist arthroscopy as the standard of reference,
      sensitivity and specificity values for SLIL perforations were 52%/34% for non
      enhanced MRI and 90%/87% for MR arthrography. CONCLUSIONS: MR arthrography, using
      three-dimensional volume acquisition with thin slices (0.6-1.0 mm), combines the
      advantages of three-compartment arthrography and non-enhanced MRI. It shows the
      precise location and magnitude of ligamentous defects of all parts of the SLIL,
      correlates well with wrist arthroscopy and has potential implications for
      diagnosis and treatment planning.

PMID- 9194227
TI  - MR imaging of supra-acetabular insufficiency fractures.
AB  - OBJECTIVE: Diagnosis of insufficiency fractures in the pelvis is difficult,
      especially in patients with prior malignancy, irradiation, steroid therapy or
      osteoporosis. This report shows the MR imaging appearance of supra-acetabular
      insufficiency fractures and how they can be differentiated from metastatic
      disease. DESIGN AND PATIENTS: Twelve patients (four men, eight women, average age
      72.8 years) at risk for pelvic insufficiency fractures and who had pelvic or hip
      pain were studied with MR imaging. Indications were possible recurrent tumor or
      previous radiation to the pelvis (7 patients); osteoporosis from steroid use in
      rheumatoid arthritis (two patients); to exclude osteonecrosis of the hip (two
      patients); or to rule out a hip fracture (one patient). RESULTS: A characteristic
      linear region of low signal intensity on both T1- and T2-weighted sequences was
      found in the supra-acetabular region paralleling the superior acetabulum in a
      curvilinear are in 92% (11/12) of cases, and oblique in origin in 8% (1/11).
      Diffuse bands of high signal on T2-weighted images indicated surrounding edema.
      In two cases, MR findings obviated biopsy. One patient underwent a biopsy prior
      to the imaging studies being reviewed. All patients were treated conservatively
      and did well. DISCUSSION: Attention to insufficiency fractures has previously
      focused on characteristic locations in the sacrum and pubic bones. Supra
      acetabular insufficiency fractures also occur and are difficult to diagnose
      without a high degree of suspicion. MR imaging is a useful tool for diagnosing
      supra-acetabular insufficiency fractures. The characteristic MR imaging
      appearance of these fractures can preclude additional diagnostic studies and
      therapy in most instances.

PMID- 9194228
TI  - Radiation-induced brachial plexopathy: MR imaging.
AB  - OBJECTIVE: To describe the MR imaging appearance of radiation-induced brachial
      plexopathy. DESIGN: MR imaging was performed in two patients with the clinical
      diagnosis of radiation-induced brachial plexopathy and in one with surgically
      proven radiation fibrosis of the brachial plexus. PATIENTS: Three patients who
      had had radiation therapy to the axilla and supraclavicular region (two with
      breast carcinoma and one with Hodgkin's lymphoma) presented with symptoms in the
      arm and hand. To exclude metastases or tumor recurrence MR imaging was performed.
      RESULTS AND CONCLUSION: In one patient, fibrosis showing low signal intensity was
      found, while in two patients high signal intensity fibrosis surrounding the
      brachial plexus was found on the T2-weighted images. In one case gadolinium
      enhancement of the fibrosis was seen 21 years after radiation therapy. It is
      concluded that radiation-induced brachial plexopathy can have different MR
      imaging appearances. We found that radiation fibrosis can have both low or high
      signal intensities on T2-weighted images, and that fibrosis can enhance even 21
      years after radiation therapy.

PMID- 9194229
TI  - Bone and soft tissue manifestations of alveolar echinococcosis.
AB  - OBJECTIVE: The present study demonstrates the osseous and soft tissue
      manifestations of alveolar echinococcosis (AE). PATIENTS: We report on eight
      patients with AE with bone or soft tissue involvement confirmed at biopsy or
      needle cytology. RESULTS: All eight patients showed hepatic involvement. Four
      exhibited infiltration of the spine as a result of direct spread of the hepatic
      primary lesion; distant metastases were observed in only three of these patients.
      Calcifications, which are typical for hepatic manifestations of the disease, were
      observed in soft tissue in only two of eight cases (25%); we observed no
      instances of endovesicular daughter cysts. CONCLUSIONS: AE manifests itself in
      the vertebral column as a form of spondylitis and in soft tissue presents similar
      to an abscess. Since in most of these cases spread of the disease per
      continuitatem from the liver is present, the diagnosis is easily made from the
      characteristic hepatic findings.

PMID- 9194230
TI  - Anteroinferior tears of the glenoid labrum: fat-suppressed fast spin-echo T2
      versus gradient-recalled echo MR images.
AB  - OBJECTIVE: To compare fat-suppressed fast spin-echo (FSE) T2-weighted images with
      gradient-recalled echo (GRE) T2*-weighted images in the evaluation of
      anteroinferior labral tears. DESIGN: MR images were retrospectively reviewed by
      two radiologists masked to the history and arthroscopic findings. They separately
      interpreted the anteroinferior labrum as torn or intact, first on one pulse
      sequence and then, 4 weeks later, on the other sequence. The MR interpretations
      were correlated with the arthroscopic findings. PATIENTS: Nine patients with
      anteroinferior labral tears, and nine similarly-aged patients with normal, labra
      were studied. RESULTS AND CONCLUSIONS: Observer 1 had a sensitivity of 0.56 on
      the GRE images and 0.67 on the FSE images (P > 0.5), with a specificity of 1.0
      for both sequences. Observer 2 had a sensitivity of 0.78 and a specificity of
      0.89 for both sequences. In this small study there is no significant difference
      between GRE and fat-suppressed FSE images in their ability to diagnose
      anteroinferior labral tears. When evaluating the labrum with conventional MRI,
      axial fat-suppressed FSE T2-weighted images can be used in place of GRE images
      without a loss of accuracy.

PMID- 9194231
TI  - Acute knee trauma: how many plain film views are necessary for the initial
      examination?
AB  - OBJECTIVE: To determine whether anteroposterior (AP) and lateral views of the
      knee are equivalent to four views in acute fracture detection. DESIGN: Three
      musculoskeletal radiologists retrospectively interpreted the plain film knee
      examinations of each patient, establishing ground truth for the presence or
      absence of a fracture. Cases were presented to four masked senior radiology
      residents twice--once as a two-view study and again as a four-view study--with 4
      weeks separating the two reading sessions to minimize recall bias. Sensitivity,
      specificity, and diagnostic performance were calculated. PATIENTS: Ninety-two
      patients presenting to the emergency department with acute knee trauma were
      evaluated with at least a four-view plain film examination. RESULTS AND
      CONCLUSIONS: Mean sensitivity for fracture detection using four views (85%) was
      significantly higher than that using two views (79%). Mean specificity and
      receiver operating characteristic curve areas were not significantly different
      using two or four views. Four views are more sensitive than AP and lateral views
      alone in detection of acute knee fracture.

PMID- 9194232
TI  - Ulnar distribution of reflex sympathetic dystrophy due to compression of the
      brachial plexus by a primary venous malformation.
AB  - An atypical variant of reflex sympathetic dystrophy (RSD) is presented in a 45
      year old female with a vascular malformation of the right arm and chest wall. The
      mechanism was thought to be compression of the brachial plexus by the
      malformation. The unique scintigraphic features of this presentation of RSD in
      the ulnar arterial distribution are illustrated.

PMID- 9194233
TI  - Transient osteoporosis of the knee.
AB  - The MR findings in transient osteoporosis of the knee have been described as
      showing a diffuse area of decreased signal intensity (relative to normal bone
      marrow) on T1-weighted images and increased signal intensity on T2-weighted
      images. We report a case of transient osteoporosis, in which MRI showed a
      crescentic area of abnormal signal intensity in the posterior portion of the
      lateral femoral condyle, which was bordered by a rim of low signal intensity,
      best seen on the T2-weighted images. This abnormality was shown to resolve on
      follow-up MR scans.

PMID- 9194234
TI  - MR diagnosis of traumatic tear of the spring ligament in a pole vaulter.
AB  - The spring ligament is a significant contributor to the stability of the talar
      head and longitudinal arch of the foot, lending importance to accurate radiologic
      diagnosis of injury. Using MR, we diagnosed a spring ligament tear with
      associated navicular dorsal subluxation, confirmed intraoperatively. To our
      knowledge, there are no previous reports of MR diagnosis of tear of the spring
      ligament.

PMID- 9194235
TI  - Enlarged peroneal process with peroneus longus tendon entrapment.
AB  - A 50-year-old man was treated conservatively for chronic bilateral ankle pain for
      several years. Plain radiographs obtained following exacerbation of symptoms
      showed bilateral enlarged peroneal processes. CT and MRI demonstrated bony detail
      of the unusual processes and also showed isolation of the peroneus longus tendons
      and associated tendinitis and partial tears.

PMID- 9194236
TI  - Iliopsoas myositis mimicking appendicitis: MRI diagnosis.
AB  - Myositis of the truncal muscles can closely mimic acute appendicitis. Myositis is
      the early stage of muscular infection. It is characterized by diffuse muscular
      pain and swelling without a distinct mass. Early diagnosis of myositis improves
      the outcome and surgical debridement is usually avoided. Pyomyositis, the
      advanced stage of the disease, can be diagnosed by MRI examination. We present a
      case of early bacterial myositis that was diagnosed by MRI.

PMID- 9194237
TI  - Mycetoma of the calf.
AB  - Actinomycetous infections typically involve either the head and neck or the
      extremities following a traumatic implantation. Classic clinical associations are
      draining sinus tracts. This case report describes the pathologic and MR findings
      of a relatively acute mycetomatous process involving the soft tissues. Pathologic
      findings in this case included an occasional granule composed of gram positive,
      thin branching elements. These and other findings were consistent with
      actinomycetes bacterium infection. The discussion centers around the use of MR,
      both with and without gadolinium, in evaluating this type of granulomatous
      infection. Infiltration of the adjacent subcutaneous tissues was easier to
      appreciate on both the T1-weighted images without gadolinium and the T1-weighted
      images with gadolinium when compared to the T2-weighted images. Signal
      characteristics as described in this case report may suggest a granulomatous
      process.

PMID- 9194238
TI  - The place of mIBG imaging in the neuroblastoma diagnostic strategy.

PMID- 9194239
TI  - Some conceptual considerations on the sense of coherence.
AB  - Aaron Antonovsky's sense of coherence (SOC) [(1987) Unraveling the Mystery of
      Health, How People Manage Stress and Stay Well, Jossey-Bass, San Francisco] ought
      to explain why some people manage stress and stay well while others break down.
      According to Antonovsky's formulation, SOC is strongly developed if a person sees
      the world as comprehensible (i.e. rational, understandable, consistent and
      predictable), as manageable, and as meaningful (i.e. challenging and that things
      are worth making commitments for). Sense of coherence has gained widespread
      attention and has been used as an explanatory variable in many studies. This
      paper discusses some aspects that have not sufficiently been considered in the
      SOC literature. First, an outline of the construct is given. Next, overlaps and
      differences with other concepts in the same domain are discussed. Little
      empirical evidence concerning the stability of SOC is available. Therefore,
      findings from experimental social psychological studies on self-esteem are
      applied to SOC. Third, it can be assumed that SOC is an attitude of people who
      are well educated, are in rather privileged societal positions, and with
      opportunities for decision-making. Finally, the empirical basis is reviewed.
      Statistical relationships between SOC and symptoms/disease are in the predicted
      direction, but due to the simultaneous assessment of variables it is open to
      debate whether a low SOC has some effect on the probability of falling ill or
      whether it is the other way around. Very high negative correlations between SOC
      and depression/anxiety suggest that the instruments used may assess the same
      phenomenon, but with inverse signs. Based on these considerations, directions for
      further research are proposed.

PMID- 9194240
TI  - The poor pay more: health-related inequality in Thailand.
AB  - This paper examines the equality of utilization for equal need and equity of out
      of-pocket expenditure for health services in a large urban area in Thailand. Data
      from a household health interview survey were used to explore patterns of
      perceived morbidity, utilization of various treatment sources, and out-of-pocket
      payment. Financial access to health care, as reflected in medical benefit/
      insurance cover, appeared to influence reported illness and hospitalization
      rates. Gross lack of access to health care amongst lower socio-economic groups
      was not the main problem in this densely populated urban area because people
      could choose and use alternative health services according to their ability and
      willingness to pay. The corollary, however, was an inequitable pattern of out-of
      pocket health expenditure by income quintile and per capita. The underprivileged
      were more likely to pay out of their own pocket for their health problems, and to
      pay out of proportion to their household income when compared with more
      privileged groups. Furthermore, the underprivileged were least likely to be
      covered by government health benefit schemes, in contrast in particular to civil
      servants, who paid less out of pocket and did not contribute to their medical
      benefit fund. The private health sector (private clinics and private hospitals)
      was the major provider of health care to urban dwellers for both outpatient and
      inpatient services. Policy options for the short and long term to improve the
      equity of payment systems for health care are discussed.

PMID- 9194241
TI  - Health-seeking strategies and sexual health among female sex workers in urban
      India: implications for research and service provision.
AB  - This paper presents and discusses selected findings from a study of health
      seeking strategies in relation to sexual health among a group of female sex
      workers in Calcutta, India. Background information on sex work and sexually
      transmitted disease in Calcutta is followed by the presentation of findings
      pertaining to women's understandings of (sexual) health, treatment-seeking and
      service utilisation. In the urban context where health services are readily
      available, patterns of initial treatment-seeking are shown to be generally
      (biomedically) appropriate, but subsequent "non-compliant" therapeutic practices
      give cause for concern. Conventional approaches to the study of "health-seeking
      behaviour" are reviewed in the light of these findings and questions raised about
      the appropriateness of approaches that focus on initial choice of treatment type
      and/or assume processes of health-seeking to be determined primarily by cultural
      "beliefs" about illness. Inherent biomedical and culturalist biases in the
      orientation of such research are shown to produce an analytic neglect of the dual
      influences of material life conditions and people's perceptions of health, rather
      than illness, upon health-related strategies. Recommendations are made for
      operational research and policy formulation on the provision of effective sexual
      health services, and implications are drawn for the scope of interventions and
      applied research directed at improving sexual health.

PMID- 9194242
TI  - Costs and benefits of improving tuberculosis control: the case of Thailand.
AB  - The study evaluates the economic costs and benefits of improving tuberculosis
      control interventions in Thailand. Provider costs are determined on the basis of
      marginal treatment costs for varying case numbers and estimates of the cost of
      required infrastructure changes. Indirect costs are calculated as income lost due
      to morbidity and premature mortality. An epidemiological model is used to
      calculate case numbers and mortality under current control conditions and a
      scenario of improved control. An improved control strategy initially leads to a
      higher number of detected cases. For longer projection periods, the
      epidemiological impact of curing a higher proportion of infectious sources
      results in lower case numbers than those expected without programme improvement.
      Model simulations show a reduction of total annual case numbers through improved
      control measures by an average 45% after a simulation period of 20 years. The
      corresponding societal savings in form of reduced indirect costs from the disease
      are U.S.$2.4 billion. Reductions in direct provider costs can be expected as a
      result of decreased numbers of detected cases for longer evaluation periods, as
      well as a lower proportion of multi-drug-resistant cases. The mean value of
      predicted savings is U.S.$8.3 million. Since this value is likely to be higher
      than the required investment in improved infrastructure, net savings can be
      expected. The result of an uncertainty analysis shows a wide range of potential
      additional costs or net savings with respect to direct provider costs. Indirect
      cost calculations show net savings for all parameter values.

PMID- 9194243
TI  - Women's perceptions of the complications of pregnancy and childbirth in two Esan
      communities, Edo state, Nigeria.
AB  - The high prevalence of maternal mortality and its causes in the developing World
      have been well established. However, this information to a large extent is on
      institutional data. Establishment of the level and social context of maternal
      mortality through community-based studies are unavailable. Recent years have
      witnessed a new approach to providing an in-depth understanding of this problem
      through community-based studies involving a multi-disciplinary approach. Built
      into this approach is the use of classical anthropological methods including
      focus group discussions. Participants expressed their perceptions of maternal
      mortality in the focus groups. Issues such as alternative modes of treating
      complications in pregnancy or delivery are also discussed. This paper examines
      the complications and modes of treatment relating to pregnancy and delivery as
      perceived by Esan women. Focus group discussions generated data for analysis. The
      women identified miscarriage, separation of the placenta, haemorrhage, obstructed
      labour, and the retention of the placenta as complications experienced in
      pregnancy, labour or delivery. Of these complications, haemorrhage was the most
      severe and devastating because it kills easily owing to the amount of blood lost.
      However, two alternative modes of treatment, traditional and modern are in use,
      the most prevalent, cheapest, easier to obtain, and most trusted being the
      traditional mode of treatment. A reduction in maternal mortality requires a
      number of strategies. The most radical of these is the recommendation that both
      traditional and modern treatments need to complement one another in the same
      health institution to ensure the maximal effectiveness of both modes of
      treatment.

PMID- 9194244
TI  - Women physicians in Quebec.
AB  - This article presents the results of a qualitative study on women physicians in
      Quebec which aimed to go beyond a mere statistical description of the tendencies
      observed in their practices. It proposes an interpretation of their discourses on
      their practice and its context bringing to light the interdependence of
      individual strategies and structural constraints. We met 30 women physicians and
      eight men physicians asking them to talk freely about their personal and
      professional experience. The data reveal how the individual characteristics and
      interests of women physicians prevail in their decisions at key moments in their
      lives which have repercussions on the shaping of their practice. These moments
      include admission into the faculty of medicine, training, professional
      orientation and the choice of a specialized field, organization of professional
      practice and personal life. The medical practice of women is constructed through
      these choices and the gender variable plays a more or less significant role at
      each stage of this construction. Their distinctive choices reflect how gender
      relations are reproduced in the private sphere and the interactions between their
      private and professional lives. According to our participants, a difference lies
      in the place occupied by their profession in women and men physicians' lives. The
      private life of women physicians appears to be closely linked to their decisions
      regarding the organization of their professional life and as a result to the
      health services they provide, suggesting they have their own way of "being a
      physician". The individual nature of the strategies they adopt can have, at a
      collective level, consequences on the planning and the distribution of medical
      resources in the publicly managed health care system in Quebec while raising the
      global issue of gendered division of labor.

PMID- 9194245
TI  - Women's hidden transcripts about abortion in Brazil.
AB  - Two folk medical conditions, "delayed" (atrasada) and "suspended" (suspendida)
      menstruation, are described as perceived by poor Brazilian women in Northeast
      Brazil. Culturally prescribed methods to "regulate" these conditions and provoke
      menstrual bleeding are also described, including ingesting herbal remedies,
      patent drugs, and modern pharmaceuticals. The ingestion of such self-administered
      remedies is facilitated by the cognitive ambiguity, euphemisms, folklore, etc.,
      which surround conception and gestation. The authors argue that the ethnomedical
      conditions of "delayed" and "suspended" menstruation and subsequent menstrual
      regulation are part of the "hidden reproductive transcript" of poor and powerless
      Brazilian women. Through popular culture, they voice their collective dissent to
      the official, public opinion about the illegality and immorality of induced
      abortion and the chronic lack of family planning services in Northeast Brazil.
      While many health professionals consider women's explanations of menstrual
      regulation as a "cover-up" for self-induced abortions, such popular
      justifications may represent either an unconscious or artful manipulation of
      hegemonic, anti-abortion ideology expressed in prudent, unobtrusive and veiled
      ways. The development of safer abortion alternatives should consider women's
      hidden reproductive transcripts.

PMID- 9194246
TI  - Female labor force participation and suicide.
AB  - To test the role conflict and role enhancement hypotheses, this paper examines
      the link between female labor force participation and suicide. Using a special
      tabulation of age/sex-specific suicide data for metropolitan areas in the United
      States, we estimate separate multivariate regression models for women and men in
      1970 and 1980. Our findings show that in 1970 the level of female labor force
      participation among married women with small children is not related to the
      female suicide rate but is related to the male suicide rate in a positive
      direction. By 1980 the relationship between female labor force participation and
      the male and female suicide rate is negative, suggesting that the well-being of
      both men and women is enhanced by role accumulation among women.

PMID- 9194247
TI  - Girls, pecking order and smoking.
AB  - Against a background of growing concern about the failure to reduce cigarette
      smoking amongst young people, particularly girls, this paper attempts to unravel
      the complex interrelationships between smoking, peer group structure and gender.
      We were particularly intrigued to explore a recent hypothesis in the literature
      that suggests that girls who smoke, far from lacking self-esteem, are more self
      confident and socially skilled than their non-smoking peers. Sociometric and
      qualitative analyses revealed that smoking behaviour was indeed shaped by gender,
      and that the psychosocial processes involved in smoking uptake may be different
      for boys and than for girls. Peer group structure, consistently described by
      young people as hierarchical, was closely related to smoking behaviour. Girls at
      the top of the social pecking order who projected an image of high self-esteem
      were identified as most likely to smoke, while only a small minority of girls
      fitted the stereotype of the young female smoker who has poor social skills and
      low self-esteem. Boys of high social status were less vulnerable, since sport and
      a desire to be fit to some extent protected them. Our findings raise fundamental
      questions about the meaning of self-esteem in relation to smoking uptake, arguing
      instead for an exploration of the term "self-worth". They suggest the need for
      health education programmes which are sensitive both to gender and to peer group
      structures.

PMID- 9194248
TI  - Long-term benzodiazepine use: factors of importance and the development of
      individual use patterns over time--a 13-year follow-up in a Swedish community.
AB  - Using data from a research registry of prescriptions, we studied benzodiazepine
      use in a Swedish community with a general population of 20,000. A sample of
      benzodiazepine users in 1976 (n = 561) aged 15 years and older was identified and
      followed for 13 years with respect to continued benzodiazepine use. A strong
      tendency towards continued use was observed. A majority of the cohort, 65%,
      continued benzodiazepine use during the first follow-up year, and 55% used
      benzodiazepines during the second. One-quarter of the sample continued using
      benzodiazepines during all years of the 13-year follow-up. One of the aims was to
      analyze factors predicting long-term benzodiazepine use. The multivariate
      analyses, using Cox regression analysis, showed that frequent/daily use and age
      were important factors. Gender and type of generic benzodiazepine were of little
      importance. Further, patients who were prescribed benzodiazepines by doctors
      working at hospitals and those who obtained prescriptions from both primary and
      hospital care physicians continued to use benzodiazepines to a greater extent
      than those patients who obtained prescriptions only from private practitioners or
      health center doctors. Another aim was to analyze to what extent long-term users
      were using these drugs on an infrequent, occasional, frequent, or daily basis and
      to what extent this use changed over time. Of those with benzodiazepine use
      persisting for eight or more years (n = 119), between one-half and two-thirds
      were frequent or daily users in each of those years. Because repeated
      measurements for the same individuals were analyzed, the generalized estimating
      equations (GEE) method was chosen for the multivariate analyses. Among long-term
      users, age, a combined use of tranquilizers and hypnotics, and prescriptions from
      more than one of the prescriber categories studied (i.e. doctors working at
      health centers, hospital doctors, and private doctors) were significant factors
      in frequent or daily use. The study also showed that frequent/daily use increased
      among the identified long-term users during the time period analyzed.

PMID- 9194249
TI  - Socioeconomic status and adolescent injuries.
AB  - Injuries are the major cause of morbidity among children and adolescents in
      developed countries, but there is a lack of consensus on the relationship between
      socioeconomic status and risk of injuries. A self-complete questionnaire survey,
      to gather information on non-fatal injuries and sociodemographic details, was
      administered in schools during April-June 1994 to a national sample of 4710
      Scottish adolescents aged 11, 13 and 15 years. Although there was no evidence of
      a socioeconomic gradient in the total incidence of medically attended injuries
      among adolescents, based on the Registrar General's classifications of paternal
      occupation and a composite measure of family affluence, marked socioeconomic
      variation in the circumstances in which injuries occurred was observed. There
      were also socioeconomic differences in the extent and type of risk behaviours
      reported by adolescents, indicating differential rates of risk exposure. The
      finding that socioeconomic status affects the kinds of injury events adolescents
      experience and levels of risk behaviour has implications for the design of injury
      prevention strategies.

PMID- 9194250
TI  - Dispersion Index: measuring trend assessment of geographical inequality in health
      -the example of under-five mortality in the Middle East/north African region,
      1980-1994.
AB  - A Dispersion Index for the measurement of geographical inequality in the
      distribution of health status indicators across space and time is proposed. The
      Dispersion Index is computed independently of the mean and is robust to changes
      in distributional shape over time. Therefore, the Dispersion Index is shown to
      possess more desirable statistical properties as compared to the coefficient of
      variation for assessing trends in the geographical distribution of health status
      indicators. Application of the Dispersion Index to the 1994 under-five mortality
      data from the Middle East/North African region shows that regional inequality in
      the distribution of under-five mortality was reduced by 47% as compared to 1980.
      Curve-fitting illustrated that the trend in the Dispersion Index values was non
      monotonic from 1980 through 1994. We suggest that apart from the World Summit for
      Children's under-five mortality target for the year 2000, intraregional targets
      to reduce geographical inequalities in under-five mortality should be specified.
      We also suggest that changes in the magnitude of the Dispersion Index be used for
      the assessment of progress made by a region or nation in achieving the specified
      numerical targets. From a policy perspective, the Dispersion Index has the
      potential to be useful in the evaluation of specific health strategies designed
      to reduce intraregional geographical inequality in the distribution of health
      status indicators within a specified period.

PMID- 9194251
TI  - The Gambian National Impregnated Bednet Programme: evaluation of the 1994 cost
      recovery trial.
AB  - Following the success of a controlled trial of insecticide-impregnated bednets in
      reducing mortality in children. The Gambia started a National Impregnated Bednet
      Programme (NIBP) in 1992. The objectives of this programme were to introduce
      impregnated bednets into all primary health care (PHC) villages and to establish
      a system of cost recovery over a three-year period. During the initial phase of
      the programme, when insecticide was given out free, a high uptake was achieved.
      However, after small user charges were introduced in 1993, coverage dropped to a
      low level. In 1994, different systems of insecticide distribution and permethrin
      formulations were tried in an attempt to improve coverage. A nationwide cross
      sectional survey carried out during the 1994 rainy season measured coverage by
      distribution channel, as well as the knowledge, attitudes and practices of health
      workers and villagers during the intervention. Overall, only 16% of bednets were
      impregnated in 1994, compared to 80% when the insecticide was offered free of
      charge in previous years. Lack of money was the major reason given by villagers
      for not impregnating their bednets in 1994. Use of impregnated bednets was higher
      in areas where the sale of permethrin emulsion by village health workers was
      supplemented by the sale of insecticide in individual packages through shops. In
      villages where insecticide was distributed free to women with small children
      through governmental mother and child health (MCH) services, higher levels of
      coverage were achieved among women and young children than in villages where
      other distribution systems were used. We conclude that the sale of insecticide
      through the private sector may increase bednet impregnation rates in African
      communities, and that the free distribution of insecticide through MCH services
      may be an effective way of targeting young children, the group most at risk of
      malaria.

PMID- 9194252
TI  - Willingness to pay for antihypertensive care: evidence from a staff-model HMO.
AB  - Willingness to pay (WTP) has been used in Sweden to evaluate the value of
      antihypertensive therapy. The Swedish studies indicate that hypertensive patients
      are willing to pay between $107 and $120 per month for their therapy. We
      conducted a similar study in a population of hypertensive patients in a large,
      staff-model, managed care organization (Group Health Cooperative of Puget Sound).
      Participants returned a postal survey containing a WTP question with 10 "bids"
      ranging from $25 to $250. Respondents recorded whether they would accept or
      reject each bid at the stated dollar value. Demographic information such as age,
      income, and perceived health status was also collected. Results were analyzed
      with ordinary least squares regression, controlling for the demographic data. The
      estimated parameters were significant and indicated an adjusted mean WTP of $93
      per month for antihypertensive therapy. The close similarity of the Swedish and
      U.S. results appears to support the use of WTP as a measure of health state
      preferences.

PMID- 9194253
TI  - Are there social correlates to suicide?
AB  - A structural-sociological approach to suicide research holds that an aggregate
      level cause of suicide should correlate with the suicide rates in a population.
      In 1980, Sainsbury, Jenkins, and Levey published the article "The Social
      Correlates of Suicide in Europe" which related the suicide rates in 1961-63 and
      the changes in them in the following 11 years to 15 social variables in 18
      European countries. Its main findings were that the changes in suicide rates
      could be attributed to specific changes in the social environment. Complementary
      discriminant analyses showed that it was possible accurately to divide the
      countries into low- and high-change suicide rate groups on the basis of a
      combination of the social variables. Although criticized for its method, the
      study has been widely quoted and sometimes presented as the most definitive
      current study on the subject. In order to see whether its results held for
      similar data 16 years later it was replicated for 1977-79 and the ensuing 11
      years, with data and method as similar as possible to the original. The results
      agreed with those of the original study on only one point: the correlations
      between the levels of the social variables and those of the suicide rates were
      similar in both periods. However, changes in the suicide rates were unrelated to
      either the levels of the social variables or the changes in them: correlations
      found in the original study tended to change profoundly or disappear. Moreover,
      the results of the original discriminant analyses were a property of the method
      employed and thus independent of the data. Statistical artefacts or social
      processes such as changing expectations are unlikely to explain the suddenly
      changing or vanishing correlations. The original correlations seem to have been
      largely spurious and dependent on the fact that the more modern countries in
      Europe experienced a "suicide boom" in the 1960s. As the boom waned in these, it
      was beginning in the less modern countries: the correlations between the
      processes indicated by the social variables and the suicide rates were reversed
      or disappeared. The results call the existence of clear relations between these
      "suicidogenic" social circumstances and the suicide rates into question. Since
      many of the variables used are traditional "Durkheimian" indicators of the
      integration of society, a critique of this still-dominant view of the
      relationship between society and suicide mortality, or its common
      operationalization, is implied.

PMID- 9194254
TI  - A call for consistency in definition of breastfeeding behaviors.

PMID- 9194255
TI  - Spinal cord injuries in Arkansas due to violence: 1980-1989.
AB  - In some areas of the US the incidence of violence-related spinal cord injuries
      (SCIs) is double or triple that of 10 years ago. The purpose of this study was to
      determine if this trend is evident in Arkansas, a small rural state. For the
      study period 15.3% of traumatic SCIs identified in Arkansas were violence
      related. The overall incidence rate of traumatic SCIs in Arkansas declined from
      41.11 per million in 1980 to 33.18 per million in 1989. However, the rate of
      violence-related SCIs rose from 3.5 per million in 1980 to 5.14 in 1989. The
      incidence of violence-related SCIs in Arkansas did not increase dramatically
      during the 1980s. However, the incidence of women with violence-related SCIs
      nearly tripled. With the dramatic rise in violence-related SCIs in women and the
      decrease in violence-related SCIs in men, the gender gap has been virtually
      eliminated in violence-related SCIs.

PMID- 9194256
TI  - Estimating social adjustment following spinal trauma--II: Population trends and
      effects of compensation on adjustment.
AB  - Adaptation to, or acceptance of, acquired spinal cord injury is accepted as an
      essentially longitudinal process. Changes in an individual's social, financial
      and domestic positions in turn affect issues concerning quality of life and self
      image. The responses of 302 individuals with spinal cord injury in the United
      Kingdom and United States of America are presented to produce individual profiles
      of social adjustment. The differences between the UK and USA groups are
      presented, together with a combined analysis which addresses, in particular, the
      effects which being involved in litigation has on the process of social
      adjustment. Individual data concerning social adjustment, provided through a
      scale developed by the authors, and the utility of graphical presentation of the
      data is also presented. Such presentation has been found to have particular
      importance in clinical interview, situations by providing a framework for further
      exploration of individual adjustment difficulties, and in legal settings.

PMID- 9194257
TI  - Clinical case of the month. Cervical vertebral fracture: orthopaedic issues.

PMID- 9194258
TI  - A prospective survey of the causes of non-traumatic spastic paraparesis and
      tetraparesis in 585 patients.
AB  - OBJECTIVE: To ascertain the relative frequencies of the causes of non-traumatic
      paraparesis and tetraparesis in adults. DESIGN: Survey of patients enrolled
      prospectively over a 3 year period between 1986 and 1989 and review of their case
      notes 1 year after enrollment ceased (mean duration of follow up 30 months).
      SETTING: Regional neurosciences centre in the UK serving over three million
      people in Merseyside and North Wales. PATIENTS: Experienced clinicians from the
      centre saw most patients in the region with non-traumatic spastic paraparesis or
      tetraparesis. Primary investigation of patients was by myelography, for which
      patients were admitted to the centre. 585 consecutive patients with spastic
      paraparesis or tetraparesis were identified by daily screening of all 2104
      patients undergoing myelography or radiculography during the 3 year period, ie
      selection by the intention to investigate them for myelopathy. EXCLUSIONS: age
      under 15 years, previous myelography for myelopathy. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Numbers and proportions of patients with each condition or
      category of disease. RESULTS: Commonest diagnoses were cervical spondylotic
      myelopathy (23.6%), extrinsic neoplastic or developmental tumour (16.4%),
      multiple sclerosis (9.1% rising to 17.8% after MRI of a selected group), and
      motor neurone disease (4.1%). Diagnosis was uncertain in 27.4%, falling to 18.6%
      after MRI. CONCLUSIONS: This survey shows the pattern of diseases producing non
      traumatic myelopathy in the Mersey Region and in North Wales. Changing patterns
      of referral, investigation in peripheral hospitals and by non neurologically
      trained practitioners, and increasing use of outpatient MRI for primary
      investigation may make comparable surveys impossible in the future.

PMID- 9194259
TI  - Recovery of bladder function in patients with acute spinal cord injury:
      significance of ASIA scores and somatosensory evoked potentials.
AB  - The significance of the ASIA (American Spinal Injury Association) scores and SSEP
      (somatosensory evoked potentials) recordings in predicting the recovery of
      bladder function was evaluated in 70 patients with acute, traumatic spinal cord
      injury (SCI). The patients were examined following admission to the
      rehabilitation centre (mean 10 days post-trauma) both clinically by the ASIA
      scores and electrophysiologically by tibial and pudendal SSEP recordings. The
      results of the initial examinations were related to the degree of recovery of
      bladder function of the patients assessed by urodynamic examination at the end of
      the rehabilitation programme (at least 6 months post-trauma). The recovery of
      somatic nerve function (external urethral sphincter function) involved in bladder
      function was correlated to both the initial ASIA scores and SSEP recordings
      (Spearman correlation, P < 0.001). The latter parameters, however, were not
      related to the outcome of autonomic nerve function (eg detrusor vesicae function)
      (Spearman correlation, P = 0.1). Therefore, the initial clinical and
      electrophysiological examinations are of value in assessment of the degree to
      which the patient will recover somatic nervous control of bladder function.
      However, these examinations are not indicative of urodynamic impairment.
      Therefore, urodynamic examination should be mandatory for the diagnostic
      assessment and therapeutical approach of bladder dysfunction in patients with
      acute SCI.

PMID- 9194260
TI  - Densitometric patterns of spinal cord injury associated bone loss.
AB  - The purpose of the study was to use dual energy X-ray absorptiometry to measure
      bone mineral density (BMD) in the lumbar spine, the femoral neck, Ward's
      triangle, and the greater trochanter in 204 men (69 able-bodies controls and 135
      spinal cord injured patients) stratified according to age (20-39, 40-59, and 60+
      years old) in order to determine whether changes in BMD were age related, and to
      determine when these changes began to appear. The BMDs of the lumbar spine of
      both the 40-59 year old and the 60+ year old patients were significantly higher
      (P < or = 0.012) than the 40-59 year old and 60+ year old controls, respectively.
      The femoral region BMDs of the 20-39 year old and the 40-59 year old patients
      were all significantly lower (P < or = 0.027) than the 20-39 year old and 40-59
      year old controls, respectively. When patients were grouped according to the time
      since their injury (0-1, 1-5, 6-9, 10-19, 20-29, 30-39, 40-49, and 50-59 years
      post injury) within the various age categories different results were obtained.
      In all the age categories, BMD loss occurred starting one year after spinal cord
      injury in the hip region. This bone loss took place gradually, reaching a
      significant plateau (P < or = 0.017) at 19 years post injury and then started
      improving. The spine BMD in our patient population never significantly decreased,
      and started improving as the age of the injury increased. Findings presented for
      the femoral regions were similar to other investigators' findings; however, the
      steady bone mass maintained in the lumbar area, which increased with age
      regardless of the age of the injury, with the bone mass loss in the hip area,
      were the most notable new findings.

PMID- 9194261
TI  - Rehabilitation of walking for paraplegic patients by means of a treadmill.
AB  - The present study was aimed at investigating the use of a treadmill for
      ambulation training of paraplegic subjects. To investigate the likely
      effectiveness of this modality of rehabilitation, six paraplegic patients (three
      male and three female) were studied, using new generation reciprocating gait
      orthoses (RGO and ARGO), in a treadmill training program. Oxygen consumption,
      heart rate, and pulmonary ventilation were measured when the subjects were
      walking at their most comfortable speed on the treadmill and on the open field.
      These measurements were carried out at the beginning of the study and after two
      and six months of treadmill training. The following findings were significant:
      the treadmill walking required 30% less energy than open field ambulation prior
      to training (P < 0.001) and 50% after training (P < 0.05). The most comfortable
      walking speed was faster on the treadmill than on the open field by 18% prior to
      training (P < 0.05) and 42% afterwards (P < 0.05). The energy cost was 50% less
      after 2 months training on the treadmill (P < 0.05) showing that treadmill
      training can improve the efficiency of over ground ambulation. It can be
      concluded that the treadmill training improves the RGO/ARGO walking capability,
      probably both the walking efficiency (short term adaptation) and physical fitness
      (long term adaptation).

PMID- 9194262
TI  - Motor, sensory and functional recovery in patients with spinal cord lesions.
AB  - The aim of this study is to evaluate the sensory, motor and functional
      improvement in patients with a Spinal Cord Lesion (SCL) by recording at
      admission, discharge and at 12 months after discharge. Fifty-five patients (29
      with paraplegia and 26 with tetraplegia) admitted to our departments of Physical
      Medicine and Rehabilitation between December 1992-1995. Three patients were
      excluded as they did not give their consent. Each patient was evaluated at
      admission, before discharge and at 12 months after discharge. Motor status was
      evaluated by the motor score (MS), sensory status by the light touch score (LTS),
      and functional status by the Functional Independence Measure (FIM) score. Each
      patient was asked to complete a patient questionnaire which was developed
      according to the standards of the American Spinal Injury Association (ASIA)
      scale. Twelve patients (10 with paraplegia and two with tetraplegia) were
      evaluated at 12 months after discharge. Paired samples t-test was used for
      statistical analysis. The mean age of the patients group was 36.42 +/- 17.70
      years, the mean duration of inpatient rehabilitation was 93.87 +/- 44.95 days.
      The SCL was due to trauma in 45 patients, 86.50% of the cases and was complete in
      nine patients (17.30%) and incomplete in 19 (36.53%) with paraplegia. Six
      tetraplegic patients (11.53%) had complete and 18 had (34.61%) incomplete
      lesions. The evaluation of MS, LTS and FIM scores at admission and discharge
      showed significant improvement in the MS and LTS in all of the patients with
      incomplete lesions (P < 0.001). FIM scores showed significant improvement only in
      those with complete or incomplete paraplegia (P < 0.05). At 12 months follow-up
      there was no significant change in the MS and the LTS whereas a significant
      change was noted in the FIM scores (P < 0.05) in 10 paraplegic patients. In
      summary, the results of this study indicate that rehabilitation was effective in
      our SCL series although the significant gain may also be attributed to the fact
      that 71.1% of the study group had incomplete neurological lesions.

PMID- 9194263
TI  - The determination of vasoactive substances during autonomic dysreflexia.
AB  - Urinary bladder percussion induced autonomic dysreflexia (AD) was observed in
      spinal cord injured patients with a complete neurological lesion, the upper level
      being above T5. To document the pathology and study the etiology of autonomic
      dysreflexia to further investigate its mechanism, this paper presents some
      clinical data on the determination of vasoactive substances such as
      norepinephrine (NE), epinephrine (E), renin (R), angiotensin II (AII) and atrial
      natriuretic polypeptide (ANP) before and during bladder percussion in 30 patients
      with a thoracolumbar or cervical spine and spinal cord injury. It is demonstrated
      that tapping the urinary bladder of such patients can cause AD. Changes of some
      of the vasoactive substances in the plasma were also observed, which might
      indicate that autonomic dysreflexia result from excitation of the sympathetic
      nervous system. Overactivity of the sympathetic nervous system was antagonized by
      excitation of the vegetative nerve system. There was no correlation between
      changes of blood pressure and adrenal function as well as the change of R-A II
      system; during autonomic dysreflexia, the inclement of ANP secretion played an
      important role in recovering homeostasis.

PMID- 9194265
TI  - Motor evoked potentials of the respiratory muscles.

PMID- 9194264
TI  - Constipation-related symptoms and bowel program concerning individuals with
      spinal cord injury.
AB  - PURPOSE: To determine the prevalence of constipation-related symptoms in
      individuals with chronic spinal cord injury (SCI), to describe the bowel program
      as reported by patients and including use of bowel medications and evacuation
      techniques, and to examine the clinical, functional and pharmacological risks of
      difficulty with evacuation. PATIENTS AND METHODS: This is a cross-sectional study
      of all in-patients at least 3 months beyond acute injury, on the West
      Roxbury/Brockton VAMC SCI Service, during a 10 month period (n = 197). Clinical,
      functional, and medication data were abstracted from medical and nursing records.
      Individual interviews were conducted with all available participants (n = 161,
      82%) regarding bowel-related symptoms and treatment over the previous 1 month
      period. The study definition of difficulty with evacuation was spending more than
      1 h per episode of bowel evacuation. RESULTS: Forty-one percent of the 161
      interview responders spent more than 1 h on bowel evacuation, 50% reported
      abdominal distension and 38% reported abdominal pain, 27% reported headaches or
      sweats relieved by having a bowel movement, and 33% reported fecal incontinence
      at least once a month. The bisacodyl suppository was the most commonly used
      laxative agent, while docusate was the most popular oral agent. Subjects with
      difficulty with evacuation (n = 66) were compared with those who spent less than
      1 h on evacuation (n = 95). Factors associated with difficulty with evacuation
      were tetraplegia, Frankel grade A/B, laxative use, polypharmacy, previous urinary
      outlet surgery, and symptoms of abdominal pain and distension. CONCLUSION:
      Constipation-related symptoms are highly prevalent in individuals with spinal
      cord injury, despite considerable laxative use. Our findings suggest that
      difficulty with evacuation can be predicted on the basis of a patient's clinical
      profile.

PMID- 9194266
TI  - Special precautions to be observed while using alprostadil in patients with
      spinal cord injury.

PMID- 9194267
TI  - Summary measures and statistics for comparison of quality of life in a clinical
      trial of cancer therapy.
AB  - Assessment of health related quality of life (QOL) has become an important
      endpoint in many clinical trials of cancer therapy. Most of these studies entail
      multiple QOL scales that are assessed repeatedly over time. As a result, the
      problem of multiple comparisons is a primary analytic challenge with these
      trials. The use of summary measures and statistics both reduces the number of
      hypotheses tested and facilitates the interpretation of trial results where the
      primary question is 'Does the overall QOL differ between treatment arms?' I
      present two classes of summary measures that are sensitive to consistent trends
      in the same direction across multiple assessment times or multiple QOL scales.
      Missing data strongly influences the choice between the two classes, where one
      class handles missing data on an individual basis, while the other class uses
      model-based strategies. I present the results from a clinical trial of adjuvant
      therapy for breast cancer that use summary measures with a focus on the practical
      issues that affect these analysis strategies, such as missing data and
      integration of QOL with efficacy endpoints such as survival.

PMID- 9194268
TI  - Effect size and power for clinical trials that measure years of healthy life.
AB  - Some clinical trials perform repeated measurements on patients over time, plot
      those measures against time, and summarize the results in terms of the area under
      the curve. If the measured variable is health status, the summary outcome is
      sometimes referred to as years of healthy life (YHL), or quality-adjusted life
      years (QALY). This paper investigates some theoretical and practical aspects of
      randomized trials designed to assess measures such as YHL. We first derived
      algebraic expressions for the effect size of YHL measures under several
      theoretical models of the treatment's effect on health. We used these expressions
      to examine how the length of the study, the number of measurements per person and
      the correlations among health measurements over time influence the effect size.
      We also explored the relative statistical power of analyses based on YHL versus
      analyses based on change-scores using the same data. We present an example.
      Findings suggest that: (i) the number of measurements per person need not be
      large; (ii) high correlation among measures over time tends to lower the power of
      a study using YHL; (iii) a longer study will not always provide more power than a
      shorter study, and (iv) analyses based on YHL may have less power than change
      score analyses. Some of these findings depend on the model of change in health
      status caused by the treatment. Such models require further study.

PMID- 9194269
TI  - Testing for treatment differences with dropouts present in clinical trials--a
      composite approach.
AB  - A major problem in the analysis of clinical trials is missing data from patients
      who drop out of the study before the predetermined schedule. In this paper we
      consider the situation where the outcome measure is a continuous variable and the
      final outcome at the end of the study is the main interest. We argue that the
      hypothetical complete-data marginal mean averaged over the dropout patterns is
      not as relevant clinically as the conditional mean of the completers together
      with the probability of completion or dropping out of the trial. We first take
      the pattern-mixture modelling approach to factoring the likelihood function, then
      direct the analysis to the multiple testings of a composite of hypotheses that
      involves the probability of dropouts and the conditional mean of the completers.
      We review three types of closed step-down multiple-testing procedures for this
      application. Data from several clinical trials are used to illustrate the
      proposed approach.

PMID- 9194270
TI  - Comparison of population pharmacokinetic modeling methods using simulated data:
      results from the Population Modeling Workgroup.
AB  - Statistical modeling methods have had increasing use in drug disposition studies,
      both to estimate pharmacokinetic parameters and to develop regression models that
      relate these parameter estimates to patient characteristics. These methods are
      particularly flexible as they allow non-linearity and sparse within-patient
      information. In the past few years, multiple analysis methods have become
      available, but there is a lack of systematic comparisons of their estimates on
      the same data sets. Two simulated data sets were therefore developed by the
      Population Modeling Workgroup of the Biopharmaceutical Section of the American
      Statistical Association. We analysed these data sets using seven population
      modeling programs, some of which contain multiple analysis methods. Although each
      data set represents a single replicate from a given model and data collection
      design, the results suggest that the behaviour of some methods differs from that
      of the others.

PMID- 9194271
TI  - A marginal regression modelling framework for evaluating medical diagnostic
      tests.
AB  - Technological advances continue to develop for early detection of disease.
      Research studies are required to define the statistical properties of such
      screening or diagnostic tests. However, statistical methodology currently used to
      evaluate diagnostic tests is limited. We propose the use of marginal regression
      models with robust sandwich variance estimators to make inference about the
      sensitivity and specificity of diagnostic tests. This method is more flexible
      than standard methods in that it allows comparison of sensitivity between two or
      more tests even if all tests are not carried out on all subjects, it can
      accommodate correlated data, and the effect of covariates can be evaluated. This
      last feature is important since it allows researchers to understand the effects
      on sensitivity and specificity of various environmental and patient
      characteristics. If such factors are under the control of the clinician, it
      provides the opportunity to modify the diagnostic testing program to maximize
      sensitivity and/or specificity. We show that the marginal regression modelling
      methods generalize standard statistical methods. In particular, when we compare
      two screening tests and we test each subject with both screens, the method
      corresponds to McNemar's test. We describe data from an ongoing audiology
      screening study and we analyse a simulated version of the data to illustrate the
      methodology. We also analyse data from a longitudinal study of PCR as a
      diagnostic test for cytomegalovirus.

PMID- 9194272
TI  - Tests of geographical correlation with adjustment for explanatory variables: an
      application to dyspnoea in the elderly.
AB  - We propose a test of correlation of the residuals in generalized linear models
      which is a generalization of the spatial autocorrelation test based on Moran's I.
      It allows adjustment for sizes of geographical areas and for explanatory
      variables. A formula is given to compute the weights according to the alternative
      hypothesis. We compare inference using the distribution in the model and using
      the permutation distribution. A simulation study showed that the model-based test
      may be very conservative and this leads to a loss of power compared to the
      permutation test or to the model-based test with correction for estimated
      parameters. As this latter is intractable for very large samples when the model
      includes explanatory variables, we recommend the use of the permutation test. The
      permutation test is used to study geographical correlation of dyspnoea in the
      elderly.

PMID- 9194273
TI  - Confidence interval estimates of an index of quality performance based on
      logistic regression models.

PMID- 9194274
TI  - Testing for individual and population equivalence based on the proportion of
      similar responses.

PMID- 9194275
TI  - Video laparoscopy for the treatment of bleeding esophageal varices.
AB  - Bleeding from esophageal varices is the major cause of death in patients with
      portal hypertension. The ideal surgical procedure should effectively control
      bleeding, with as little impairment of liver function as possible and with low
      rates of encephalopathy. Based on this objective, we propose the azygoportal
      disconnection (APD) with splenic artery ligation, and suturing of the gastric and
      esophageal varies without opening the esophagus, by video laparoscopy. With the
      patient placed in a semigynecologic position, we use five trocars, and the
      intervention begins by dissection of the diaphragmatic hiatus and isolation of
      the esophagus. Then devascularization of the gastric fundus is accomplished.
      After that, dissection and ligature between clips of the splenic artery are
      performed. The surgery proceeds with dissection and ligation of the vessels of
      the lesser curvature. After orally introducing a 12-mm Fouchet probe, we suture
      the varices of the distal esophagus transmurally, with interrupted sutures. The
      procedure is accomplished with a floppy Nissen valve. Between March 1994 and May
      1995, four patients were treated with this method, two men and two women with a
      mean age of 54 years. All of them had hepatic cirrhosis. Three patients were
      classified Child B and the other Child C. Surgical indication in all subjects was
      persistent bleeding of the esophageal varices, after failure of such clinical
      attempts as endoscopic sclerosis and tamponade with the Sangstaken-Blakemore
      balloon. The operation mean time was 177 min. Neither bleeding nor hemodynamic
      changes occurred during the surgery. The patients were sent to the intensive care
      unit (ICU) postoperatively for a mean time of 3 days, and they were discharged
      from the hospital between days 8 and 10. The evolution demonstrated stabilization
      of the hepatic function and regression of the varices from grades III and IV to
      grade I. No bleeding recurred. Although this study had a small number of
      patients, we believe that this operation made by mini-invasive technique permits
      a quick recovery, reducing the global morbidity of this procedure.

PMID- 9194276
TI  - Mesh infections after laparoscopic inguinal hernia repair.
AB  - Several complications like hematoma and seroma have been reported after
      laparoscopic inguinal hernia repair (LH). Sepsis due to infection of the patch is
      an uncommon complication. In this retrospective trial, we evaluated three male
      patients who developed postoperative mesh infection after LH by transabdominal
      preperitoneal patch (TAPP) technique in two institutions. Diagnosis was confirmed
      by clinical symptoms, signs, ultrasonography, and computerized tomography (CT),
      and definitive treatment was provided by removing the mesh. In the first case,
      mesh infection occurred 10 months after laparoscopic left inguinal hernia repair
      with TAPP for recurrence. The infection manifested itself as an external fistula
      at the drain site. The mesh was removed laparoscopically due to persistent
      suppuration. In the second case, mesh infection occurred 3 months after
      transabdominal preperitoneal hernia repair on the left. The patch was removed
      because of the persistent suppuration despite repetitive drainage and lavage. In
      the third case, mesh infection occurred in 15 days after transabdominal
      preperitoneal hernia repair on the right. External drainage was performed under
      CT guidance, but suppuration could not be stopped. Thus the mesh was removed. In
      three cases, infection could not be stopped after diagnosis despite drainage and
      antibiotic coverage, and then it was decided to remove the mesh. The meshes were
      removed under general anesthesia for the first two cases and under local
      anesthesia for the third one. During the follow-up period, no recurrences were
      noted. The mesh infections of these three cases, resistant to conservative
      treatment methods, completely disappeared after mesh removal.

PMID- 9194277
TI  - Laparoscopic cholecystectomy in patients with cardiac disease: hemodynamic
      advantage of the abdominal wall retraction method.
AB  - We examined the use of an abdominal wall retraction method instead of
      pneumoperitoneum in laparoscopic cholecystectomy for patients with cardiac
      disease to prevent the hemodynamic deterioration associated with
      pneumoperitoneum. Eight patients with cardiac diseases, mainly valvular or
      coronary artery diseases, underwent laparoscopic cholecystectomy under
      hemodynamic monitoring. Five patients without cardiac disease served as controls.
      As hemodynamic parameters, heart rate, mean systemic arterial pressure (mAP),
      mean pulmonary arterial pressure (mPAP), central venous pressure (CVP), pulmonary
      capillary wedge pressure (PCWP), and cardiac index (CI) were measured. The
      patients with cardiac disease showed significantly elevated mPAP and PCWP
      compared with the control group under pneumoperitoneum, and one patient showed
      critically decreased CI due to increased tricuspid regurgitation under
      pneumoperitoneum. These changes, however, were resolved on the abdominal wall
      retraction. There was no major perioperative complication. This abdominal wall
      retraction method is, therefore, favorable for patients with underlying cardiac
      disease to minimize the hemodynamic deterioration during laparoscopic
      cholecystectomy.

PMID- 9194278
TI  - Case report of pediatric laparoscopic splenectomy with technical review.
AB  - Laparoscopic splenectomy has been accepted as a feasible extension of minimally
      invasive surgery, which has undergone dramatic improvements in both technology
      and instrumentation. We performed a laparoscopic splenectomy in a 7-year-old girl
      with hereditary spherocytosis. The patient recovered rapidly and returned to
      unrestricted activities quickly. The appropriate positioning of each laparoscopic
      port is essential for a good operative view and smooth access. It is also
      important to dissect the hilum of the spleen meticulously. Laparoscopic
      splenectomy in the pediatric age group appears to be another promising extension
      of laparoscopic surgery.

PMID- 9194280
TI  - Laparoscopic splenectomy for chronic idiopathic thrombocytopenic purpura.
AB  - Since October 1994, we have performed 15 laparoscopic splenectomies for
      idiopathic thrombocytopenic purpura. All the patients were women, aged 23 to 47
      years. We used five ports (three 10-mm ports and two 5-mm ports) for the first
      eight cases, but we could save one 10-mm port after changing patient's position
      from supine to the right lateral kidney position. There was no case of conversion
      to exploratory laparotomy. The mean hospital stay was 6 days. No significant
      perioperative morbidity or mortality was associated with the surgery. Since
      undergoing laparoscopic splenectomy, 12 patients have been off steroids, two
      patients have been on small doses of steroids, and one patient has been on the
      same dose of steroid with no response. Laparoscopic splenectomy is a relatively
      safe and reasonable operative procedure for the patient with idiopathic
      thrombocytopenic purpura or normal-sized spleen.

PMID- 9194279
TI  - Reactive pleuropericarditis following laparoscopic fundoplication.
AB  - Postpericardiotomy syndrome is not uncommon following cardiac surgery. The
      syndrome is characterized by fever, chest pain, leucocytosis, and signs of
      pericardial and pleural effusions. A patient with similar symptoms after
      laparoscopic treatment of reflux esophagitis is reported. Antibiotic treatment
      had no effect on a suspected bacteriological infection. There was a dramatic
      clinical response to corticosteroid treatment. The etiology and pathogenesis of
      the syndrome are discussed.

PMID- 9194281
TI  - Thoracoscopic thoracic splanchnicectomy for chronic pancreatitis with intractable
      abdominal pain.
AB  - The therapeutic advantages of a thoracoscopic thoracic splanchnicectomy (TTS) to
      relieve the pain of chronic pancreatitis patients was evaluated. The TTS
      procedure (four bilateral and five unilateral TTS), was performed on nine
      patients from April 1993 to October 1995. Based on radiographic images, the
      pancreatic duct of seven cases were diagnosed as being "nondilated" (<3 mm),
      whereas two cases were "dilated" (> or = 3 mm). A 5-mm thoracoscope was
      introduced through the fifth intercostal space on the anterior axillary line, and
      an additional two cannulas were introduced under direct thoracoscopic vision. The
      sympathetic chain, at a level from Th 5 to 9, was then resected and
      electrocoagulated. We performed a unilateral TTS corresponding to the symptomatic
      side; however, if pain relief was insufficient, an additional sympathectomy was
      done on the other side. The early postoperative course was uneventful, and
      immediate pain-relief was normally possible after TTS except for three patients
      who demonstrated minor intercostal neuralgia at the site of the trocars inserted
      for TTS. Six of nine patients were able to return to their preoperative work of
      lifestyle at a maximum follow-up of 24 months (the median and mean durations were
      15.0 and 13.7 months, respectively). In addition, no postoperative deterioration
      of either the endocrine or exocrine function of the pancreas was observed. In
      conclusion, TTS proved to be a safe and reliable procedure for the pain relief of
      the chronic pancreatitis.

PMID- 9194282
TI  - Video-assisted thoracoscopic lobectomy for treating lung cancer.
AB  - Our objective was to evaluate the usefulness and safety of video-assisted
      thoracoscopic surgery (VATS) for performing pulmonary lobectomy in 11 patients
      with clinical NO stage I primary non-small-cell lung cancer compared with 11
      patients who underwent a conventional thoracotomy. Treatment was switched to
      conventional thoracotomy in three VATS patients because of the involvement of
      interlobar nodes or incomplete lobar fissure. None of the eight VATS patients
      died or experienced serious complications during 12 months of follow-up. There
      were no significant differences in the intraoperative blood loss, duration of
      operation, or duration of chest tube drainage between the VATS group and the
      standard lobectomy group. We conclude that although VATS lobectomy appears to be
      safe for use in managing patients with primary lung cancer, it does not seem to
      offer any advantages over standard lobectomy.

PMID- 9194283
TI  - Prophylactic laparoscopic ovarian ablation for premenopausal breast cancer:
      medical and economic efficacy.
AB  - Worldwide analysis showed a highly significant reduction in the annual rates both
      of recurrence and of death produced by ovarian ablation. We examined the safety,
      efficacy, and cost-effectiveness of prophylactic laparoscopic oophorectomy for
      premenopausal breast cancer. Prophylactic laparoscopic oophorectomy was attempted
      in 15 selected premenopausal patients with breast cancer. After mastectomy, these
      patients had laparoscopic ovarian ablation as treatment for breast carcinoma with
      positive estrogen receptors. To evaluate the economic impact of laparoscopic
      oophorectomy, comparisons were made between patients treated laparoscopically and
      those treated with conventional surgery, chemotherapy, and hormonal therapy. The
      average time required for laparoscopic bilateral oophorectomy was 44 min. Oral
      intake was resumed the next morning, and the patients were discharged 3 days
      after surgery. No limitation on physical activity and no complications were
      required during postoperative days. There was no reduction in the overall costs
      of laparoscopic surgery and conventional surgery in Japan. The cost of one year's
      supply of tamoxifen was equivalent to the overall cost of surgical oophorectomy.
      From medical and economic viewpoints, we conclude that laparoscopic ovarian
      ablation should be considered an alternative to adjuvant chemotherapy in
      premenopausal women.

PMID- 9194284
TI  - Laparoscopy and septic dissemination caused by perioperative perforation of the
      occluded small bowel: an experimental study.
AB  - Based on the observation of septic shock and severe respiratory impairment in two
      patients subjected to laparoscopic surgery for small bowel occlusion, an
      experimental study was carried out in rabbits to evaluate the effect of intra
      abdominal CO2 hyperpressure on massive bacterial spread. Increased bacterial
      access to the blood was observed as a result of the mechanical effect of the
      hyperpressure associated with the highly septic contents of the occluded bowel.
      The important risk of bacterial dissemination following accidental peroperative
      perforation requires extreme caution in the laparoscopic management of late
      occlusions of the small intestine.

PMID- 9194285
TI  - Surgical laparoscopy with intraoperative manometry in the treatment of esophageal
      achalasia.
AB  - The aim of this study was to describe and evaluate the laparoscopic treatment of
      esophageal achalasia in nine patients over a 35-month period. Five trocars were
      used to perform a Heller's myotomy to completely eliminate the cardial high
      pressure zone, under manometric control. Intraoperative manometry also was used
      to calibrate a pick degrees 360 Rossetti's antireflux wrap. A complete regression
      of symptoms was observed postoperatively in seven of nine patients (77.8%); in
      two patients (22.2%) a moderate dysphagia persisted, but it disappeared 3 and 6
      months, respectively. Only one intraoperative complication (esophageal
      perforation, recognized and laparoscopically repaired) occurred. At the present
      follow-up of 18 +/- 5.34 months (range 6-35), no dysphagia or symptoms related to
      reflux have been observed. Laparoscopic treatment of esophageal achalasia is
      considered a safe and effective procedure, and the results of this procedure are
      comparable with those of the open technique. Advantages common to other
      laparoscopic techniques are emphasized.

PMID- 9194286
TI  - Video assisted thoracoscopic management of primary spontaneous pneumothorax.
AB  - Although Video-Assisted Thoracoscopic Surgery (VATS) is now accepted by many as
      the approach of choice in the management of primary spontaneous pneumothorax
      (PSP), the optimal procedure and the timing of surgical intervention remain areas
      of contention. The authors reviewed their combined experience with 518
      consecutive VATS procedures for PSP in 483 patients. Mechanical pleurodesis was
      performed in every case and was the only procedure in 20 patients. We had
      experience with several means of eliminating subpleural bullae once identified:
      stapled bullectomy (196), endoloop (261), argon beam coagulation (6) and
      endoscopic suturing (35). There were no mortality or intraoperative
      complications. Median postoperative hospital stay was 3 days. So far, we have had
      9 recurrences (1.74%), after a mean follow up of 20 months (range one to 36
      months). Complications consisted of 18 persistent air leaks, 14 would infections
      and 1 chest wall bleeding. We conclude that (1) VATS is a safe and effective
      approach in the treatment of PSP; (2) Stapled-bullectomy is quick and reliable
      but costly; (3) Endoloop and suturing are viable alternative techniques that may
      prove to be more cost effective; (4) we do not recommend to use argon beam
      coagulation as the primary treatment modality.

PMID- 9194287
TI  - Thoracoscopic major lung resection--indications, technique, and early results:
      experience from two centers in Asia.
AB  - The application of video-assisted thoracic surgery (VATS) to major lung resection
      is controversial. We reviewed our combined experience in this technique from two
      centers in Asia. From January 1993 to December 1995, 78 patients (44 male and 34
      female patients with ages ranging from 16 to 85 years) successfully underwent
      VATS major lung resections. Selection criteria for this approach include (a)
      lesions < 5 cm in maximal diameter; (b) for primary lung carcinomas, clinical
      stage I status; (c) absence of chest wall involvement; (d) absence of pleural
      symphysis; and (e) complete or near complete interlobar fissures. Procedures
      included segmentectomy (1), lobectomy (69), bilobectomy (2), and pneumonectomy
      (6) together with mediastinal lymph node sampling in cases of primary malignancy.
      We emphasized not spreading ribs and using conventional thoracic instruments for
      dissection together with wound protection on specimen retrieval. There was one
      perioperative death and five nonfatal complications that included persistent air
      leak over 10 days in two patients, pneumonia in one, and persistent dysesthesia
      related to surgery in two. We conclude that VATS major lung resection is
      technically feasible. Stringent patient selection is important. Specific
      complications exist and special training is needed. The exact role of this
      approach in thoracic surgery remains to be defined by prospective randomized
      study compared with conventional thoracotomy with long-term follow-up.

PMID- 9194288
TI  - Trends in resident experience in open and laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy (OC) as the
      most common operation for gallbladder disease. Our goal was to determine the
      effect of this phenomenon on resident training in biliary surgery. The numbers of
      all cholecystectomies (ACs), OCs, LCs, and advanced procedures (common bile duct
      exploration and choledochoscopy, (CBDE) performed by residents during academic
      years 1989 to 1994 were examined. Trends for the residency as a whole and for
      each cohort of residents completing the program were studied. The number of LCs
      performed by the residency as a whole per academic year over the 1989 to 1994
      period has increased, whereas the number of OCs decreased. The net effect of
      these trends was an increase in the number of ACs. Although the percentage of LCs
      performed by postgraduate year 1, 2, and 3 residents (juniors) increased over the
      study period, the proportion of OCs and ACs performed by this group decreased.
      For each cohort of residents completing training in the years 1989 through 1994,
      the number of ACs and LCs performed increased, whereas the number of OCs
      decreased. Experience in CBDE for the residency as a whole and for the cohort was
      stable. In conclusion, experience in ACs and LCs has increased, and experience in
      OCs has decreased. Also, experience in biliary surgery has shifted to the senior
      level.

PMID- 9194289
TI  - Common bile duct stones in acute biliary pancreatitis: an endoscopic study.
AB  - The knowledge of the natural history of common bile duct stones in biliary
      pancreatitis may be helpful in the debate concerning the timing of endoscopic
      sphincterotomy in relation to surgery. The endoscopic cholangiographies of 211
      patients with biliary pancreatitis were analyzed. The presence of bile duct
      stones was recorded, as well as the time interval between admission and
      endoscopic retrograde cholangiopancreatography (ERCP). The predicted severity of
      pancreatitis was determined by the modified Glasgow criteria. The overall
      incidence of bile duct stones was 28.9%. This incidence was 43.8% during the
      first 2 days and decreased to < 20% after 1 week. There was no correlation
      between the severity of disease and the presence of bile duct stones. The
      performance of an ERCP 1 week after the admission for biliary pancreatitis will
      avoid a substantial number of unnecessary endoscopic sphincterotomies. Prediction
      of the severity of disease does not alter the yield of bile duct stones.

PMID- 9194290
TI  - Vascular complications in minimally invasive surgery.
AB  - Injuries to major vessels in the course of laparoscopic surgery are rare but
      serious, life-threatening complications. We report nine iatrogenic vascular
      injuries during minimally invasive surgery that occurred between January 1991 and
      December 1995 in surgical and obstetric-gynecologic services in the Austrian
      province of Styria. The total vascular complication rate is 0.08%. As these data
      show, the distal abdominal aorta and vena cava, as well as the large pelvic
      vessels, are especially susceptible to injury when the Veress needle and trocars
      are inserted into the abdomen. Surgical reconstruction of these eight arterial
      lesions required a polytetrafluorethylene (PTFE) patch in one case, and the
      resection of the damaged section of the artery and reanastomosis in two others.
      The remaining lesions, as well as an isolated vein injury, were corrected with
      direct suturing of the vessel. Pelvic circulation was completely restored in all
      patients, and permanent damage was avoided.

PMID- 9194291
TI  - Lymphocytic subpopulation changes after open and laparoscopic cholecystectomy: a
      prospective and comparative study on 38 patients.
AB  - Up to now it has been unclear whether laparoscopic surgery has fewer
      immunosuppressive effects than traditional laparotomic procedures. In a series of
      38 patients affected by symptomatic gallstone disease and operated on either by
      laparoscopy (group 1) or by traditional open surgery (group 2), we determined the
      postoperative changes in lymphocyte subpopulations up to postoperative day (POD)
      30. We collected 15 ml of venous blood from all patients in both groups on the
      day before surgery and on POD 1, 7, 15, and 30. A control group (group 3)
      comprised 56 healthy volunteers; the control group was used only to ensure that
      baseline values were totally comparable with a normal population; only one blood
      sample was obtained from the subjects in group 3. Patients undergoing open
      cholecystectomy had a significant decrease in total lymphocyte count on POD 1.
      Basal levels of lymphocyte subpopulations did not differ significantly in the
      study and control groups. No differences were found in the preoperative
      lymphocyte cell counts in the two groups who underwent cholecystectomy. Pan-T
      cells (CD3) showed a statistically significant marked reduction throughout the
      observation period. The counts of helper (CD4), suppressor (CD8), and natural
      killer NK (CD16) T cells were reduced on POD 1; the NK cell (CD16) count remained
      low until POD 30, B lymphocytes showed no postoperative reduction. In patients
      who underwent laparoscopic cholecystectomy, a significant postoperative decrease
      in total lymphocyte count, and in CD3, CD4, and CD8 subpopulations was observed
      on day 1 only. There was no reduction in CD16 and CD19 subpopulations. A
      comparative statistical analysis of lymphocyte subpopulations in the two groups
      was carried out: In the open cholecystectomy group, compared with the laparoscopy
      group, CD3, CD4, CD8, and CD16 lymphocyte subpopulations showed marked reductions
      at different time points. In particular, statistically significant differences
      were found in CD3 levels from POD 1 through POD 30, in CD4 from day 1 through day
      7, and in CD8 and CD16 only on day 1.

PMID- 9194292
TI  - Infected hydrocele following laparoscopic appendectomy: case report.
AB  - In the literature, specific reported complications after laparoscopic
      appendectomy include bowel injury, hemorrhage, wound infection, and cecal
      fistula. We report the occurrence of infected hydrocele after laparoscopic
      appendectomy in a 20-year-old man. This complication, to our knowledge, has not
      yet been described in the literature.

PMID- 9194293
TI  - Double cystic duct found by intraoperative cholangiography in laparoscopic
      cholecystectomy.
AB  - We report a rare case of double cystic duct in a 74-year-old woman. The patient
      complained of mild epigastric discomfort, and several stones were discovered by
      ultrasonography and computed tomography. Any anomalies of the biliary tract were
      undetectable in the preoperative examinations without direct cholangiography.
      Laparoscopic cholecystectomy was performed. After clipping the cystic duct close
      to the gallbladder, as usual, serial intraoperative cholangiography was performed
      and unexpectedly showed the inflow of contrast medium into the gallbladder via
      another cystic duct arising from the right hepatic duct, thus revealing one
      gallbladder and two cystic ducts, one of which joined the common hepatic duct and
      the other the right hepatic duct. There was only one cystic artery that arose
      from the right hepatic artery and accompanied the primary cystic duct to be
      distributed to the gallbladder. The existence of contrast medium in the resected
      specimen was confirmed by radiography. No complications occurred during or after
      laparoscopic cholecystectomy. This is the first report of double cystic duct
      found in laparoscopic cholecystectomy. We recommend routine preoperative or
      intraoperative cholangiography.

PMID- 9194294
TI  - Laparoscopic diagnosis of appendicovesical fistula in a pediatric patient.
AB  - Appendicovesical fistula is a rare complication of acute appendicitis in children
      that is difficult to diagnose preoperatively. A 21-month-old boy with signs and
      symptoms of recurrent urinary tract infections underwent abdominal
      ultrasonography, computed tomography (CT), barium enema examination, and
      cystography, none of which was sufficient to establish a diagnosis; an
      appendicovesical fistula was demonstrated by laparoscopy. The patient underwent
      open appendectomy, with resection of the fistula through a small incision, and
      has recovered without complications.

PMID- 9194295
TI  - Duplicate gallbladder during laparoscopic cholecystectomy.
AB  - Congenital duplication of a gallbladder is a rare anatomic malformation. This
      malformation is rarely diagnosed preoperatively and usually is discovered during
      the course of cholecystectomy. Whether discovered preoperatively or
      intraoperatively, biliary anatomy should be assessed, then cholecystectomy should
      be performed on both gallbladders. Reported is a case of a duplicate gallbladder
      managed by performance of laparoscopic cholecystectomy.

PMID- 9194296
TI  - Life-threatening tension pneumothorax during laparoscopic cholecystectomy.
AB  - We report an instance of life-threatening tension pneumothorax during
      laparoscopic cholecystectomy. Such complications are rare but can be catastrophic
      without rapid intervention and management. The introduction of new technology
      should serve to obviate such problems in the future.

PMID- 9194297
TI  - Effects of fleece soiling and skinning method on the microbiology of sheep
      carcases.
AB  - The fleece of sheep becomes soiled primarily on the abdomen and on the legs. A
      five-category scoring scale for soiling of the fleece was defined, with score 1
      being clean and dry and score 5 being wet and heavily soiled with faecal
      material. Twenty sheep with each fleece score were slaughtered and dressed on a
      commercial 'inverted' slaughter line. Swab samples were taken from the shoulder
      and the abdomen of the carcases immediately after skinning, and total viable
      counts and the numbers of Enterobacteriaceae were determined. The condition of
      the fleece significantly affected the microbial load on these parts of the
      dressed carcase, with the carcases derived from sheep with increasingly dirty
      fleeces carrying up to 1000 times more microorganisms, and a higher proportion of
      the carcases being contaminated with Enterobacteriaceae. Modifications to the
      dressing procedure were made to try to reduce carcase contamination at the
      shoulder. The application of bulldog clips to prevent direct contact between the
      fleece and the underlying muscles resulted in higher counts on carcases with a
      fleece score of 3, probably owing to contamination from the hands of the
      slaughterman and the problems with ensuring that the clips were in place before
      contamination had occurred. Delaying the skinning of the shoulder until later in
      the pelt removal process achieved worthwhile reductions in the contamination of
      the shoulder of carcases with a fleece score of 4, although the total viable
      counts were still higher than carcases with a score of 3.

PMID- 9194298
TI  - Laminitis in young dairy calves fed a high starch diet and with a history of
      bovine viral diarrhoea virus infection.
AB  - Six of the 33 calves born in a Swedish dairy herd during a period of four months
      developed laminitis when they were eight to 12 weeks old. The clinical signs
      included difficulty in rising, a stiff gait, overgrown claws and haemorrhages in
      the sole horn. Samples of blood were taken from four of the calves when they had
      shown signs of laminitis for two to seven weeks; the serum concentrations of
      calcium, phosphorus and vitamin D3, the activities of aspartate aminotransferase
      and glutathione peroxidase, and the patterns of serum proteins were within their
      normal ranges. The feet of the same four calves were examined after slaughter;
      the third phalanx of each calf was rotated and its distal end osteolytic.
      Histologically there was separation and degeneration of the squamous cells of the
      white line, and thromboses and vasculitis in the fine vessels of the corium. Four
      of the six affected calves were persistently infected with bovine viral diarrhoea
      virus and one had antibodies against the virus. From six weeks of age the calves
      had been fed rye wheat, a hybrid seed rich in starch, and this may have
      contributed to the outbreak of laminitis.

PMID- 9194299
TI  - Resistance of the red poultry mite to pyrethroids in France.
AB  - The resistance of Dermanyssus gallinae, the red poultry mite, to a pyrethroid
      acaricide, permethrin, and to an organophosphate, dichlorvos, was examined on
      five French poultry farms which had experienced problems in controlling mite
      populations and on one farm with no problems. The concentration of permethrin
      required to kill 50 per cent of the mites on the five farms was between eight and
      40 times the concentration required on the control farm. In contrast, no
      resistance to dichlorvos was detected. This is the first description of
      resistance to a pyrethroid in D gallinae in France.

PMID- 9194300
TI  - Estimate of direct financial losses due to porcine proliferative enteropathy.

PMID- 9194301
TI  - Evidence of Theileria buffeli infection in cattle in southern Italy.

PMID- 9194302
TI  - Lipomatosis causing tumour-like swelling of a mandibular salivary gland in a dog.

PMID- 9194303
TI  - Isolation of Staphylococcus chromogenes from an unusual case of impetigo in a
      goat.

PMID- 9194304
TI  - Caseous lymphadenitis: an increasing cause for concern.

PMID- 9194305
TI  - Infectious pustular vulvovaginitis/infectious pustular balanoposthitis in cattle.

PMID- 9194306
TI  - Correction of tendon contracture in calves.

PMID- 9194309
TI  - 'Gut-tie' in steers.

PMID- 9194308
TI  - Frozen tail or limber tail in working dogs.

PMID- 9194310
TI  - A neural model of foveal light adaptation and afterimage formation.
AB  - Psychophysical research has documented the existence of three processes in light
      adaptation: a fast subtractive process, a divisive process that is fast at light
      onset and slower at light offset, and a very slow subtractive process (Hayhoe et
      al., 1987). In the neural model developed here, the fast subtractive process is
      identified with horizontal cell feedback onto cones and the divisive process with
      amacrine cell feedback onto bipolar cells. The very slow subtractive process is
      identified with the modulatory feedback circuit from amacrines via interplexiform
      cells to horizontal cells. A nonlinear dynamical model is developed incorporating
      these aspects of retinal circuitry along with both ON- and OFF-center M and P
      pathways. This model is shown to account for many aspects of foveal light
      adaptation, including negative afterimage formation, and to explain a number of
      the physiological differences between M and P ganglion cells, including their
      differing contrast-response functions.

PMID- 9194311
TI  - Expression of GABA in the fetal, postnatal, and adult human retinas: an
      immunohistochemical study.
AB  - The expression of GABA in the human fetal (12-25 weeks of gestation), postnatal
      (five-month-old), and adult (35-year-old) retinas was investigated by
      immunohistochemistry. GABA expression was seen as early as 12 weeks in the
      undifferentiated cells of the inner neuroblast zone; a few optic nerve fiber
      layer axons were clearly labeled, suggesting that some of the stained cell bodies
      were prospective ganglion cells, others could be displaced amacrine cells. From
      16-17 to 24-25 weeks, intense labeling was found in the amacrine, displaced
      amacrine, and some ganglion cells. During this time period, horizontal cells
      (identified by calbindin immunohistochemistry), undergoing migration (periphery)
      and differentiation (center), expressed GABA prominently. In the postnatal
      retina, some horizontal cells were moderately labeled, but very weakly in a few
      cells, in the adult. The Muller cells developed immunoreactivity first weakly at
      12 weeks and then moderately from 16-17 weeks onward. The staining was also
      evident in the postnatal and adult retinas, showing labeled processes of these
      glial cells. Virtually no axons in the adult optic nerve and nerve fiber layer
      were stained; the staining was restricted to a few, large ganglion cells and
      displaced amacrine cells: Some amacrines were also labeled. The possibility that
      GABA might play a role in horizontal cell differentiation and maturation is
      highlighted. Other evidences suggest that GABA might play a role in metabolism
      during retinal development.

PMID- 9194312
TI  - The human fetal retinal nerve fiber layer and optic nerve head: a DiI and DiA
      tracing study.
AB  - The organization of the primate nerve fiber layer and optic nerve head with
      respect to the positioning of central and peripheral axons remains controversial.
      Data were obtained from 32 human fetal retinae aged between 15 and 21 weeks of
      gestation. Crystals of the carbocyanine dyes, DiI or DiA, and fluorescence
      microscopy were used to identify axonal populations from peripheral retinal
      ganglion cells. Peripheral ganglion cell axons were scattered throughout the
      vitreal-scleral depth of the nerve fiber layer. Such a scattered distribution was
      maintained as the fibers passed through the optic nerve head and along the optic
      nerve. There was a rough topographic representation within the optic nerve head
      according to retinal quadrant such that both peripheral and central fibers were
      mixed within a wedge extending from the periphery to the center of the nerve.
      There was no indication that the fibers were reorganized in any way as they
      passed through the optic disc and into the nerve. The present results suggest
      that any degree of order present within the fiber layer and optic nerve is not an
      active process but a passive consequence of combining the fascicles of the
      retinal nerve fiber layer. Optic axons are not instructed to establish a
      retinotopic order and the effect of guidance cues in reordering fibers,
      particularly evident prechiasmatically and postchiasmatically, does not appear to
      be present within the nerve fiber layer or optic nerve head in humans.

PMID- 9194313
TI  - Changing topography of the RPE resulting from experimentally induced rapid eye
      growth.
AB  - The retinal pigment epithelium (RPE) of the quokka wallaby. Setonix brachyurus,
      grows and changes throughout life. To investigate factors that determine changes
      in the quokka RPE, we have examined topography of this tissue in experimentally
      enlarged eyes. Unilateral eyelid suture was conducted at the time of normal eye
      opening, postnatal day (P) 110, and animals were examined at 1 or 1 1/2 years of
      age. The numbers and densities of RPE cells and the extent of multinucleation
      were compared with those in normal animals. Eyelid suture resulted in a 9.8% and
      17.4% increase in retinal area at 1 and 1 1/2 years, respectively; a significant
      degree of myopia was associated with this enlargement. Cell density topography in
      experimental eyes was not the same as in controls. Cells from central retina were
      disproportionately larger in the experimental than control eyes. However, the RPE
      cell topography in sutured eyes was not the same as that of aged retinae of a
      similar size. Notably, in sutured eyes there was no development of the high or
      highest cell densities seen in equatorial and temporal central RPE in aged
      retinae, respectively. Furthermore, the degree of cell enlargement in peripheral
      regions was slight compared with that observed in similar-sized, aged retinae.
      There was no increase in RPE cell number; rather, average cell area increased
      accompanied by no change or a slight decrease in RPE thickness. Consequently,
      overall volume of cells did not change significantly. The large number of
      multinucleate cells normally seen in aged animals was not observed in
      experimentally enlarged eyes, implying that an increase in cell volume may be the
      trigger for multinucleation.

PMID- 9194314
TI  - Tracer coupling among regenerated amacrine cells in the retina of the goldfish.
AB  - This study sought to characterize the tracer coupling of regenerated amacrine
      cells in the retina of the goldfish and assess the integration of regenerated
      neurons into existing retinal circuits. Regeneration of new neurons from injury
      induced progenitors was stimulated by surgically excising a small rectangular
      piece of retina. Several months after regeneration was complete, intracellular
      injections of Neurobiotin, a gap junction-permeant tracer, were made into single
      regenerated amacrine cells or nonregenerated (extant) amacrine cells lying
      outside the regenerated patch. Two groups of amacrine cells were injected: those
      that in normal retina are tracer coupled and a single type (the radiate amacrine
      cell) that is not. The data show that regenerated amacrine cells are tracer
      coupled to each other and to their homologous counterparts outside the patch of
      regenerated retina. Regenerated radiate cells possess morphologically abnormal
      dendrites, but these processes can extend out of regenerated retina into
      surrounding normal retina. Similarly, the dendrites of extant radiate cells,
      severed by the original lesion, can regenerate into the patch of regenerated
      retina. These results indicate that in the goldfish retina the cell-specific
      junctional circuitry present in normal retina is re-created in the regenerated
      retina, and suggest that regenerated neurons are functionally integrated into the
      existing retina.

PMID- 9194315
TI  - The DAPI-3 amacrine cells of the rabbit retina.
AB  - In the rabbit retina, the nuclear dye, 4,6,diamidino-2-phenylindole (DAPI),
      selectively labels a third type of amacrine cell, in addition to the previously
      characterized type a and type b cholinergic amacrine cells. In this study, these
      "DAPI-3" amacrine cells have been characterized with respect to their somatic
      distribution, dendritic morphology, and neurotransmitter content by combining
      intracellular injection of biotinylated tracers with wholemount
      immunocytochemistry. There are about 100,000 DAPI-3 amacrine cells in total,
      accounting for 2% of all amacrine cells in the rabbit retina, and their cell
      density ranges from about 130 cells/mm2 in far-peripheral retina to 770 cells/mm2
      in the visual streak. The thin varicose dendrites of the DAPI-3 amacrine cells
      form a convoluted dendritic tree that is symmetrically bistratified in S1/S2 and
      S4 of the inner plexiform layer. Tracer coupling shows that the DAPI-3 amacrine
      cells have a fivefold dendritic-field overlap in each sublamina, with the gaps in
      the arborization of each cell being occupied by dendrites from neighboring cells.
      The DAPI-3 amacrine cells consistently show the strongest glycine
      immunoreactivity in the rabbit retina and they also accumulate exogenous [3H]
      glycine to a high level. By contrast, the AII amacrine cells, which are the best
      characterized glycinergic cells in the retina, are amongst the most weakly
      labelled of the glycine-immunopositive amacrine cells. The DAPI-3 amacrine cells
      costratify narrowly with the cholinergic amacrine cells and the On-Off direction
      selective ganglion cells, suggesting that they may play an important role in
      movement detection.

PMID- 9194317
TI  - Physiology of the A1 amacrine: a spiking, axon-bearing interneuron of the macaque
      monkey retina.
AB  - We characterized the light response, morphology, and receptive-field structure of
      a distinctive amacrine cell type (Dacey, 1989), termed here the A1 amacrine, by
      applying intracellular recording and staining methods to the macaque monkey
      retina in vitro. A1 cells show two morphologically distinct components: a highly
      branched and spiny dendritic tree, and a more sparsely branched axon-like tree
      that arises from one or more hillock-like structures near the soma and extends
      for several millimeters beyond the dendritic tree. Intracellular injection of
      Neurobiotin reveals an extensive and complex pattern of tracer coupling to
      neighboring A1 amacrine cells, to two other amacrine cell types, and to a single
      ganglion cell type. The A1 amacrine is an ON-OFF cell, showing a large (10-20 mV)
      transient depolarization at both onset and offset of a photopic, luminance
      modulated stimulus. A burst of fast, large-amplitude (approximately 60 mV) action
      potentials is associated with the depolarizations at both the ON and OFF phase of
      the response. No evidence was found for an inhibitory receptive-field surround.
      The spatial extent of the ON-OFF response was mapped by measuring the strength of
      the spike discharge and/or the amplitude of the depolarizing slow potential as a
      function of the position of a bar or spot of light within the receptive field.
      Receptive fields derived from the slow potential and associated spike discharge
      corresponded in size and shape. Thus, the amplitude of the slow potential above
      spike threshold was well encoded as spike frequency. The diameter of the
      receptive field determined from the spike discharge was approximately 10% larger
      than the spiny dendritic field. The correspondence in size between the spiking
      receptive field and the spiny dendritic tree suggests that light driven signals
      are conducted to the soma from the dendritic tree but not from the axon-like
      arbor. The function of the axon-like component is unknown but we speculate that
      it serves a classical output function, transmitting spikes distally from
      initiation sites near the soma.

PMID- 9194316
TI  - Concentrations of biogenic amines in fundal layers in chickens with normal visual
      experience, deprivation, and after reserpine application.
AB  - Previous experiments in chickens have shown that dopamine released from the
      retina may be one of the messengers controlling the growth of the underlying
      sclera. It is also possible, however, that the apparent relationship between
      dopamine and myopia is secondary and artifactual. We have done experiments to
      assess this hypothesis. Using High Pressure Liquid Chromatography with
      electrochemical detection (HPLC-ED), we have asked whether changes in dopamine
      metabolism are restricted to the local retinal regions in which myopia was
      locally induced. Furthermore, we have measured the concentrations of biogenic
      amines separately in different fundal layers (vitreous, retina, choroid, and
      sclera) to find out how changes induced by "deprivation" (= removal of high
      spatial frequencies from the retinal image by translucent eye occluders which
      produce "deprivation myopia") are transmitted through these layers. Finally, we
      have repeated the deprivation experiments after intravitreal application of the
      irreversible dopamine re-uptake blocker reserpine to see how suppression of
      dopaminergic transmission affects these changes. We found that (1) Alterations in
      retinal dopamine metabolism were indeed restricted to the retinal areas in which
      myopia was induced. (2) The retina was the major source of dopamine release with
      a steep gradient both to the vitreal and choroidal side. Vitreal content was
      about one-tenth, choroidal content about one-third, and scleral content about one
      twentieth of that of the retina. (3) There was a drop by about 40% in vitreal
      dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanilic acid)
      concentrations following deprivation which occurred already at a time where
      little changes could yet be seen in their total retinal contents. (4) Choroidal
      and scleral dopamine levels were not affected by deprivation, indicating that
      other messengers must relay the information to the sclera. (5) A single
      intravitreal injection of reserpine lowered dopamine and HVA levels in retina and
      vitreous for at least 10 days in a dose-dependent fashion and diminished or
      suppressed further effects of deprivation on these compounds. DOPAC levels
      continued to change upon deprivation even after reserpine injection (Fig. 3). Our
      results suggest that the release rates of dopamine from retinal amacrine cells
      can be estimated from vitreal dopamine concentrations; furthermore, they are in
      line with the hypothesis that there is an inverse relationship between dopamine
      release and axial eye growth rates. Although our experiments do not ultimately
      prove that dopamine has a functional role in the visual control of eye growth,
      they are in line with this notion.

PMID- 9194318
TI  - Regional specialization in the eye of the sphingid moth Manduca sexta: blue
      sensitivity of the ventral retina.
AB  - The compound eye of the tobacco hornworm moth Manduca sexta contains green-, blue
      , and ultraviolet-sensitive photoreceptors. Electroretinogram spectral
      sensitivity measurements were recorded from different regions of the retina in
      order to broadly map the distribution of the three receptor types. The relative
      contribution of the three receptors to spectral-sensitivity curves was estimated
      by fitting theoretical curves based on the absorption spectra of the three
      rhodopsins. This analysis indicated that the dorsal retina is green and
      ultraviolet dichromatic, with green-sensitive cells greatly predominating. The
      ventral retina is trichromatic with a substantial population of blue- and
      ultraviolet-sensitive receptors. We previously showed that flower visitation for
      nectar feeding is mediated mainly by blue-sensitive cells. Their localization in
      the ventral retina seems an appropriate adaptation of the receptor mosaic, since
      the moths hover above flowers as they feed.

PMID- 9194319
TI  - Depth perception and evoked brain activity: the influence of horizontal disparity
      and visual field location.
AB  - The perception of dynamic random-dot stereograms (RDS) depends on the
      physiological fusion of horizontally disparate binocular visual input. Thus, the
      use of RDS offers the possibility to study selectively cortical processing of
      visual information in man. We investigated the influence of horizontal disparity
      on the scalp topography of RDS evoked brain activity in 33 healthy subjects.
      Stereoscopic checkerboard patterns were presented in the center or lateralized in
      the left or right visual field with horizontal disparities changing at temporal
      frequencies of six or eight depth reversals/s using different disparity values
      ranging from 3.5 to 28 min of arc. In 11 subjects evoked potential fields were
      recorded from 16 electrodes, and 21 subjects participated in 30-channel
      recordings with electrodes located over the parietal and occipital brain areas.
      Stimulation frequency-related brain activity was obtained with all disparity
      values; however, with large or small disparities the potential field strength
      decreased significantly while largest responses were obtained with intermediate
      disparities. Significant differences were observed in RDS evoked brain activity
      when central and lateralized stimulus locations were compared. With lateral
      stimuli (extending from the fovea to 17.1-deg eccentricity) maximal amplitudes
      were obtained at larger disparities than with central stimuli. In addition there
      were pronounced differences between brain activity evoked with stimuli presented
      in the left or right visual field; however, there were very similar evoked
      potential signals recorded from electrodes located over the left and right
      hemispheres. Our findings indicate that the processing of disparity information
      with lateralized stimuli is different from the processing in the center of the
      visual field. In addition, lateralized stimulation yields a significant disparity
      tuning mainly with stereoscopic targets occurring to the right from the fixation
      point (but not with stimuli to the left) suggesting a functional difference
      between the visual half-fields.

PMID- 9194320
TI  - A comparison of the components of the multifocal and full-field ERGs.
AB  - The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs.
      The purpose here was to compare the components of this multifocal ERG to the
      components of the standard, full-field ERG. To record multifocal ERGs, an array
      of 103 hexagons was displayed on a monitor. Full-field (Ganzfeld) ERGs were
      elicited by flashes presented upon steady background fields. The latencies of two
      prominent subcomponents of the full-field ERG were altered by varying the
      intensity of the incremental flash or the intensity of the background field. By
      showing that similar manipulations of the multi-input parameters produce similar
      changes in latency, we were able to relate the components of the multifocal ERG
      to the components of the full-field ERG. The biphasic responses of the multifocal
      ERG appear to be generated by the same cells generating the a-wave and positive
      peaks of the full-field cone ERG.

PMID- 9194321
TI  - Immunocytochemical localization of dopamine D1 receptors in the retina of
      mammals.
AB  - Dopamine is one of the major neurotransmitters in the retina. It is released from
      amacrine and interplexiform cells into both inner (IPL) and outer (OPL) plexiform
      layers. Several dopaminergic actions are known to occur through D1 receptors
      (D1R) but the precise location of these receptors has not been established. An
      antibody that recognizes the intracytoplasmic C-terminal of the rat D1R was used
      to detect D1R, immunohistochemically, in rats (Wistar and RCS), mouse, hamster,
      and macaque monkey retinas. The OPL was heavily stained in each species,
      consistent with the known actions of dopamine on horizontal cells. Three to five
      bands were observed in the IPL, depending on species. Three were in the a
      sublayer, the outermost of which was close to the amacrine cell layer, and may
      represent the massive dopamine input to the AII rod-amacrine cells. As observed
      in mice, where bipolar cells are D1-immunoreactive, the band located in sublayer
      3 of the IPL may contain cone-bipolar cell terminals. A band of D1R
      immunoreactivity in the b sublayer of the IPL contains ON-bipolar cell terminals
      and a second site of interaction between dopaminergic cells and the AII amacrine
      cells. This sublayer was absent from the RCS rat retina, suggesting a severe
      impairment of the rod-driven pathway following rod degeneration in these mutant
      rats. Cells in the ganglion cell layer exhibited relatively heavy staining, and
      may be ganglion cells or displaced amacrine cells. Some extrasynaptic
      localizations of D1R in the retina are suggested.

PMID- 9194322
TI  - Serial inhibitory synapses in retina.
AB  - Whole-cell voltage clamp in the retinal slice and intracellular current clamp in
      the intact retina were used to study inhibitory interactions in the inner
      plexiform layer. Picrotoxin or strychnine reduced inhibitory, light-evoked
      currents in a majority of ganglion cells. However, in nearly a third of the
      ganglion cells, each of these antagonists enhanced the inhibitory synaptic
      current. All inhibitory current was blocked by the addition of the other
      antagonist. This indicates a cross-inhibition between GABAergic and glycinergic
      feedforward pathways. Blocking of GABAARs with SR95531 shortened the time course
      of both excitatory and inhibitory synaptic currents in ganglion cells.
      Application of picrotoxin, which blocked both GABAARs and GABACRs, produced the
      opposite effect. Recordings in the intact retina indicated that the light
      responses of ON bipolar cells, sustained ON, and transient ON-OFF third-order
      neurons were all made more transient by SR95531 and made more sustained by
      picrotoxin. The data suggest that a GABAC feedback pathway to bipolar cells makes
      light responses more phasic and that this feedback is inhibited through a GABAAR
      pathway. Consequently, the balance between GABAAR and GABACR inhibition regulates
      the time course of inputs to ganglion cells.

PMID- 9194323
TI  - Light-induced modulation of coupling between AII amacrine cells in the rabbit
      retina.
AB  - The rod-driven, AII amacrine cells in the mammalian retina maintain homologous
      gap junctions with one another as well as heterologous gap junctions with on-cone
      bipolar cells. We used background illumination to study whether changes in the
      adaptational state of the retina affected the permeabilities of these two sets of
      gap junctions. To access changes in permeability, we injected single AII amacrine
      cells with the biotinylated tracer, Neurobiotin, and measured the extent of
      tracer coupling to neighboring AII cells and neighboring cone bipolar cells. We
      also measured the center-receptive field size of AII cells to assess concomitant
      changes in electrical coupling. Our results indicate that in well dark-adapted
      retinas, AII cells form relatively small networks averaging 20 amacrine cells and
      covering about 75 microns. The size of these networks matched closely to the size
      of AII cell on-center receptive fields. However, over most of their operating
      range, AII cells formed dramatically larger networks, averaging 326 amacrine
      cells, which corresponded to an increased receptive-field size. As the retina was
      light adapted beyond the operating range of the AII cells, they uncoupled to form
      networks comparable in size to those seem in well dark-adapted retinas. Our
      results, then, indicate that the adaptational state of the retina has a profound
      effect on the extent of electrical coupling between AII amacrine cells. Although
      we observed light-induced changes in the number of tracer-coupled cone bipolar
      cells, these appeared to be an epiphenomenon of changes in homologous coupling
      between AII amacrine cells. Therefore, in contrast to the robust changes in AII
      AII coupling produced by background illumination, our data provided no evidence
      of a light-induced modulation of coupling between AII cells and on-cone bipolar
      cells.

PMID- 9194324
TI  - Dynamic shifts of the contrast-response function.
AB  - We recorded visual evoked potentials in response to square-wave contrast-reversal
      checkerboards undergoing a transition in the mean contrast level. Checkerboards
      were modulated at 4.22 Hz (8.45-Hz reversal rate). After each set of 16 cycles of
      reversals, stimulus contrast abruptly switched between a "high" contrast level
      (0.06 to 1.0) to a "low" contrast level (0.03 to 0.5). Higher contrasts
      attenuated responses to lower contrasts by up to a factor of 2 during the period
      immediately following the contrast change. Contrast-response functions derived
      from the initial second following a conditioning contrast shifted by a factor of
      2-4 along the contrast axis. For low-contrast stimuli, response phase was an
      advancing function of the contrast level in the immediately preceding second. For
      high-contrast stimuli, response phase was independent of the prior contrast
      history. Steady stimulation for periods as long as 1 min produced only minor
      effects on response amplitude, and no detectable effects on response phase. These
      observations delineate the dynamics of a contrast gain control in human vision.

PMID- 9194325
TI  - Solar pruning of retinal rods in albino rainbow trout.
AB  - Morphology of the central retina and scotopic visual sensitivity were compared in
      juvenile albino and normally pigmented rainbow trout living under natural and
      reduced daylight. Outdoor albinos avoided exposing their eyes to direct sunlight,
      whereas normals were indifferent to it. After 4 months outdoors (approximately
      10,000 lux in albinos, approximately 100,000 lux in normals), albinos had
      severely truncated or missing rod outer segments (ROS) and some missing rod
      ellipsoids, but normal numbers of photoreceptor nuclei and fully intact cones.
      Albino estimated ROS volume was only 7.1% of normal in July, but increased to 20%
      by the following February, mainly via an increase in numbers of ROS. However, in
      albinos moved indoors October 7 and exposed to 10-30 lux ambient daylight, both
      the number and length of ROS increased significantly, with estimated ROS volume
      reaching 95% of normal by 34 days. Albinos generally had more phagosomes
      (approximately 3 x normal) and more macrophages (approximately 2 x normal) in
      their outer retina. An optomotor reflex was used to define the effect of ROS
      volume on the ability to respond visually during dark adaptation. In July,
      albinos and normals from outdoor raceways (3 months) or indoor raceways (35 days)
      showed equal sensitivity after first being placed in darkness, but after 1 h in
      darkness, outdoor albinos with 6% of normal ROS volume were 2.0 log units less
      sensitive than indoor or outdoor normals, whereas indoor albinos with 53% of
      normal ROS volume were only 0.7 log units less sensitive. This verifies that most
      rod cell bodies of albino trout can persist without functional ROS in indirect
      sunlight, and can regrow functional outer segments in dim daylight. This finding
      is distinct from the extensive retinal light damage observed in albino rats
      exposed to more moderate cyclic light, in which entire rod cells degenerate early
      on.

PMID- 9194326
TI  - Characterization of aldehyde dehydrogenase-positive amacrine cells restricted in
      distribution to the dorsal retina.
AB  - A class 1 aldehyde dehydrogenase (ALDH) catalyzes oxidation of retinaldehyde to
      retinoic acid in bovine retina. We used immunocytochemistry and in situ
      hybridization to localize this enzyme in adult and fetal bovine retinas. Specific
      ALDH immunoreactivity was present in the cytoplasm of wide-field amacrine cells
      restricted in distribution to the dorsal part of the adult retina. The somata
      diameters ranged from approximately 8 microns to approximately 15 microns, and
      the cells increased in density from approximately 125 cells/mm2 near the
      horizontal meridian to approximately 425 cells/mm2 in the superior far periphery.
      The ALDH-positive cells had somata on both sides of the inner plexiform layer
      (IPL) and processes in two IPL strata. The majority of ALDH-positive cells were
      unreactive with antibodies against known amacrine cell enzymes and
      neurotransmitters, including GABA and glycine. The ALDH-positive amacrine cells
      also did not react with anti-cellular retinoic acid-binding protein, which was
      present in a subset of GABA-positive amacrine cells. In flat-mounted retinas
      processed by in situ hybridization, the larger ALDH-positive amacrine cells
      tended to be more heavily labeled. In addition to amacrine cells, Muller cell
      processes in the inner retina were weakly immunoreactive for ALDH; however, these
      glial cells did not contain ALDH mRNA. The pattern of ALDH expression in fetal
      bovine retinas was documented by immunocytochemistry. No ALDH reactivity was
      found before 5.5 months; for the remainder of the fetal period, ALDH
      immunoreactivity was present in amacrine cells similar to those in adult retina.
      The ALDH-positive amacrine cells in bovine retina are novel, being limited in
      distribution to the dorsal retina and unlabeled with other amacrine cell-specific
      markers. Identification of ALDH in amacrine cells provides additional evidence
      that cells of the inner retina are involved in retinoid metabolism.

PMID- 9194327
TI  - Investigations of the ongoing stressful situations among those with chronic
      illness.
AB  - This paper examines methods of adaptation among those faced with stress from
      chronic health problems. Studies of disabled older adults and those with muscular
      skeletal disorders are described with special emphasis on the role of everyday
      life events, and the threats to well-being imposed by chronic stressors.
      Attention is paid not only to psychological distress as outcome of a failure to
      adapt, but also to indices of psychological well-being which provide evidence of
      the benefits for those who cope successfully with chronic illness. The paper
      examines evidence for the proposition that everyday stressors can influence
      physiological processes linked to disease course. The implications of these
      findings for social interventions are discussed from community and health
      psychology perspectives.

PMID- 9194328
TI  - Protective factors and young adolescent tendency to abstain from alcohol use: a
      model using two waves of intervention study data.
AB  - Two waves of data from a family-focused preventive intervention project were used
      to test a model of the influence of protective factors on young adolescents'
      tendency toward alcohol abstinence. Prior theoretical and empirical work guided
      the specification of hypothesized effects of the protective factors affectional
      relationship with parents, affiliation with prosocial peers, and mastery-esteem
      on tendency toward alcohol abstinence. The tested model controlled for
      preintervention measures and included specified interrelations of protective
      factors across time. Structural equation analysis indicated that the model fit
      the data. Two of the hypothesized cross-time effects, however, were not
      supported.

PMID- 9194329
TI  - Patterns of adolescent involvement in problem behaviors: relationship to self
      efficacy, social competence, and life events.
AB  - Using a sample of 556 adolescents from a suburban community, patterns of various
      adolescent problem behaviors (e.g., delinquent behavior, smoking, use of alcohol
      or drugs) and their links to self-efficacy, social competence, and life events
      were examined. Cluster analysis was conducted to identify four subgroups of
      adolescents who showed distinct patterns of problem behaviors. These clusters
      were compared on the measures of self-efficacy, social competence, and life
      events. Overall results suggest there are meaningful links between adolescents'
      problem behavior patterns and self-efficacy, the amount and quality of
      participation in various after school activities, and life events. For example, a
      subgroup of adolescents who showed uniformly low prevalence of all problem
      behaviors reported more positive academic self-efficacy, more active
      participation in sports and nonsports activities, more positive life events, and
      fewer negative events than adolescents who were involved in multiple problem
      behaviors. Implications for prevention and future research on adolescent problem
      behaviors are discussed.

PMID- 9194330
TI  - System influences on posthomicide beliefs and distress.
AB  - Criminal justice system experiences in 150 family members of homicide victims
      were investigated. The study had two goals: (a) to document the experiences of
      homicide survivors in the criminal justice system, including case outcomes,
      criminal justice system activities, and satisfaction with system personnel; and
      (b) to determine if experiences with the police impacted posthomicide beliefs
      (cognitive assumptions about the world and one's relationship to it) and
      psychological distress. The sample, which was identified through the Medical
      Examiner's Office, was drawn from all criminal homicides from 1.5 to 5 years
      prior to selection. Results showed that family members of homicide victims were
      very dissatisfied with their experiences in the criminal justice system.
      Additionally, whereas objective system outcomes (e.g., arrest) did not directly
      affect posthomicide beliefs and distress, subjective system outcomes (e.g.,
      police satisfaction) directly affected beliefs and indirectly affected distress.
      There was some support for both equity theory and a cognitive theory of change,
      the two theories that guided the model specification.

PMID- 9194331
TI  - Unique hearing protection devices--the search for a balance.

PMID- 9194332
TI  - [Production of antibody against cytosolic 54 kDa protein in rat liver--evidence
      of the significant induction by a highly toxic coplanar polychlorinated
      biphenyl].
AB  - We have reported that a 54 kDa protein in rat liver cytosol is highly inducible
      by treatment with 3,3',4,4',5-pentachlorobiphenyl (PenCB) or 3-methylcholanthrene
      (MC) using SDS-polyacrylamide gel electrophoresis. Internal amino acid sequences
      of this protein in the rat liver were highly homologous to those of selenium
      binding protein (SeBP) or acetaminophen binding protein (APBP) in mouse liver
      cytosol. In this paper, the purification and characterization of this protein
      were demonstrated. MC was given at a dose of 20 mg/kg for 3 consecutive days. The
      liver cytosolic 54 kDa protein was purified twice from the MC-treated male Wistar
      rats by Rotofore Cell procedure to apparent single on SDS-polyacrylamide gel
      electrophoresis, and the rabbit antiserum against this protein was obtained. Male
      Wistar rats were given PenCB in corn oil at a single dose of 25 mg/kg i.p. The
      liver cytosol was prepared on the 5th day after the treatment and subjected to
      immunoblot analysis. The 54 kDa protein was markedly induced in the liver cytosol
      of PenCB-treated rats. Immunoblot analysis after two-dimensional gel
      electrophoresis suggested that there could be isoforms of 54 kDa protein. The
      induction of the 54 kDa protein with PenCB was assumed to be mediated through Ah
      receptor. The physiological role of the 54 kDa protein was discussed together
      with SeBP and APBP, the role of which has not yet been elucidated.

PMID- 9194333
TI  - [Effect of co-planar polychlorinated biphenyl on the hepatic glutathione
      peroxidase redox system in rats and guinea pigs].
AB  - The effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on hepatic glutathione
      peroxidase (GPx) redox system was studied in vivo in rats and guinea pigs. PCB
      126 treatment caused significant reduction of Se-dependent and -non-dependent GPx
      activity in rats. In agreement with this, the content of glutathione (GSH) and
      the activities of GSH reductase (GR) and gamma-glutamyl transpeptidase (gamma
      GTP) were also decreased in this species. On the contrary, guinea pig liver Se
      non-dependent GPx activity was significantly enhanced by PCB 126 treatment, while
      no effect on Se-dependent activity was observed. Neither the content of GSH nor
      the enzyme activities responsible for GSH supply in guinea pig liver was affected
      by PCB 126. These result suggested that the damage on GPx redox system is, at
      least, one of mechanisms by which co-planar PCB induces the toxicity in rats.
      However, in guinea pigs, this is not the case, and different mechanism from the
      damage on active oxygen quenching system is likely to be involved.

PMID- 9194334
TI  - [The condition of PCBs and PCDFs in the blood of Yusho patients 20 years after
      the onset].
AB  - Blood samples of Yusho and control persons were analyzed for individual congeners
      of PCDDs, PCDFs, and PCBs by high resolution GC/MS. Concentrations of 2,3,4,7,8
      penta-CDF, 1,2,3,4,7,8-hexa-CDF and 2,3,3',4,4',5-hexa-CB in Yusho blood were up
      to 56 times higher than the corresponding concentrations in the control blood.
      These high concentrations have persisted for 23 years after the incident.
      Concentrations of 3,3',4,4',5-penta-CB and 2,3',4,4',5-penta-CB in some Yusho
      blood were lower than the control blood. In Yusho blood, 2,3,4,7,8-penta-CDF
      contributed the highest toxicity (TEQ 77-248 ppt in lipid) among the congeners
      determined and toxic contribution of PCDFs was very large (41-77%) in the
      chlorinated pollutants. Thirty PCB congeners were identified in the blood of
      Yusho patients in 1996 by GC/MS. The average total PCB concentration in Yusho
      blood were 4.9 times higher than that of the controls. Characteristic PCB
      congeners in Yusho patients were 2,2',3,4,4',5-hexa-CB, 2,3,3',4,4',5-hexa-CB and
      2,3,3',4,4',5'-hexa-CB and their concentration ratios to the controls were 8-19.

PMID- 9194335
TI  - [Tissue distribution of methylsulfonyl metabolites derived from Kanechlor 400 in
      mice].
AB  - Kanechlor 400, which caused the "Yusho disease", was i.p. administered to mice
      and methylsulfonyl (MeSO2) metabolites were investigated with respect to the
      concentration in liver and lung during 28 days after the administration. Major
      components were 3- and 4-MeSO2 derivatives from seven PCBs (IUPAC no. #31, #49,
      #64, #70, #101, #110, #132). In the liver, similar concentration ratio of 3- and
      4-MeSO2 derivatives was observed, whereas seven 4-MeSO2 derivatives were
      selectively retained in the lung. Methylsulfone metabolites of triCB (#31) were
      rapidly formed and eliminated. The highest concentration of the metabolites in
      the lung was 4-MeSO2-2, 2', 4', 5-tetraCB. Concentration ratio of MeSO2-CBs to
      residual PCBs was 1:2.1 in the liver whereas 4.6:1 in the lung 28 days after the
      administration.

PMID- 9194336
TI  - [Effect of green tea (matcha) on gastrointestinal tract absorption of
      polychlorinated biphenyls, polychlorinated dibenzofurans and polychlorinated
      dibenzo-p-dioxins in rats].
AB  - This paper presents the liver distribution and fecal excretion of polychlorinated
      biphenyls (PCB), polychlorinated dibenzofurans (PCDF) congeners and
      polychlorinated dibenzo-p-dioxins (PCDD) congeners, in male rats fed with
      powdered green tea (matcha). The rats were given a treatment diet containing 10%
      matcha for the first five days. Then, the animals were administered 4 g of 10%
      matcha diet containing 0.5 ml of the casual rice-bran oil of Yusho that had
      occurred in the Southwest part of Japan in 1968 and kept on the same diet for
      another five days. The fecal excretion of PCB, PCDF and PCDD in the group fed
      with 10% matcha were 4.4, 2.4-9.1 and 2.5-4.7 times higher (p < 0.01),
      respectively, than that in the control group. The liver distribution of PCB, PCDF
      and PCDD in the same groups were 79%, 20-75% and 26-67% of the control group,
      respectively. These findings suggest that administration of matcha is useful as a
      treatment of Yusho patients exposed to PCB, PCDF and PCDD.

PMID- 9194337
TI  - [Concentrations of PCDDs, PCDFs and coplanar PCBs in blood of 83 patients with
      Yusho].
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), coplanar polychlorinated biphenyls (Co-PCBs) and total
      polychlorinated biphenyls (PCBs) were analyzed in blood samples from 83 Yusho
      patients and 39 normal control subjects in 1995. The average concentrations of
      PCDDs, PCDFs and Co-PCBs in the blood of Yusho patients were 14, 128 and 14 pg
      toxic equivalent quantity (TEQ)/g, lipid, respectively. The levels of these
      compounds in the blood of normal subjects were 14, 10 and 8 pg/g lipid,
      respectively. Thus, although the average levels of PCDDs and Co-PCBs in the blood
      of Yusho patients were similar to those of control subjects, the PCDF level in
      Yusho patients was 12.8 fold higher than in normals. Average concentrations of
      total PCBs in the blood of Yusho patients and normal control subjects were 789
      and 339 ng/g lipid, respectively. Thus, the PCB level in the blood of Yusho
      patients was 2.3 fold higher than in normal subjects. To test the reproducibility
      of determination of PCDDs, PCDFs and Co-PCBs, three normal blood samples were
      analyzed twice. These analyses gave similar results each time. Since, these
      compounds could be measured in five-milliliter blood samples, they can be
      monitored in Yusho patients.

PMID- 9194338
TI  - [Levels of PCDDs, PCDFs and coplanar PCBs in sebum and blood of Yusho patients].
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) and it's related compounds such as
      polychlorinated dibenzofurans (PCDFs) can be detected in the body in Yusho
      patients, a condition caused by ingestion of contaminated rice oil with these
      compounds. These compounds are excreted out of the body in small amounts directly
      in the feces from the wall of the intestine. We found the PCDDs, PCDFs and
      coplanar polychlorinated biphenyls (Co-PCBs) in the sebum of Yusho patients and
      normal subjects, and there was significant correlation between their
      concentrations in sebum and blood in both patients and normal control subjects.
      The concentration of TEQ (toxic equivalent quantity of 2,3,7,8-tetrachlorodibenzo
      p-dioxin: TCDD) in sebum of Yusho patients (106 pg/g lipid) was half that in the
      blood (215 pg/g lipid), while that of normal subjects (29 pg/g lipid) was similar
      to that in the blood (34 pg/g lipid). On the other hand, in Yusho patients the
      concentrations of TEQ in the sebum and in blood were 2.3 and 6.4 fold higher than
      those in normal subjects. We concluded that dioxins and it's related compounds in
      Yusho patients and normal subjects were excreted not only in the feces but also
      in the sebum.

PMID- 9194339
TI  - [Stimulation for sebum excretion of PCDDs, PCDFs and coplanar PCBs on bathing
      ceramic sand bath].
AB  - We previously reported that high risk environmental contaminants such as
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs)
      and coplanar polychlorinated biphenyls (PCBs) are excreted not only in feces but
      also in the sebum of the face and body in both normal subjects and Yusho
      patients. A combination of administration of rice bran fiber and cholestyramine
      increased fecal excretion of PCDFs and PCBs. In the present study, we stimulated
      excretion of these compounds in sebum using a ceramic sand bath, a kind of sand
      bath using small ceramic balls (3.5 mm diameter) instead of natural sand. Five
      normal volunteers participated in this experiment. Sebum eliminated from the body
      on bathing ceramic sand bath was collected and weighed and then concentrations of
      the compounds interest in the sebum were determined. We also examined the effects
      varying the bath conditions such as temperature of sand, length of bathing time
      and frequency of taking bath on the amounts of the compounds in the eliminated
      sebum. The results can be summarized as follows: 1. The average amount of sebum
      per one bath eliminated from the body during the ceramic sand bath was 0.252 g,
      and those of PCDDs, PCDFs and coplanar PCBs in it were 2.2, 2.0 and 2.2 pg of TEQ
      (2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent quantity). It was considered that
      the amounts of these compounds corresponded to between one quarter and third of
      those eliminated through the sebum in a day. On the other hand, 0.05 g of the
      sebum was collected from the face during the bath, included 0.39, 0.39 and 0.59
      pg TEQ for PCDDs, PCDFs and coplanar PCBs, respectively. 2. As the number of
      bathing times a day increased, the amount of sebum per bath gradually decreased.
      However, we could not determine the influence of the conditions of the bath such
      as temperature and time.

PMID- 9194340
TI  - Induction of micronuclei in cultured human lymphocytes with the mixture of highly
      toxic organochlorine compounds retained in human body.
AB  - In this study, we investigated the effect of mixture of the organochlorine
      compounds, which very resembled their contamination profile of healthy Japanese
      people in its composition, on the induction of micronuclei in human whole-blood
      cultures in order to clarify their genotoxicity as a whole. The following results
      were obtained. Regardless of the presence or absence of 7, 8-benzoflavone (ANF)
      in the blood culture system, we observed a fairly good dose-response relationship
      between the concentration of the mixture and the induction of micronuclei. In
      particular, we found that 50% effective concentration of the mixture of the
      organochlorine chemicals was considered only about 7 times greater level over the
      average concentration in the healthy people, namely 70ppt as 2, 3, 7, 8-TCDD, in
      the absence of ANF and about 5 times more than that in the presence of ANF. Based
      on these results, the mixture was regarded as extremely genotoxic. Our human
      bodies, however, have already been contaminated with a variety of chemicals
      including PCDDs, PCDFs and Co-PCBs and accordingly one of the most important
      problems to be solved is a further comprehensive genotoxicity and health
      consequences due to these chemicals to the descendants.

PMID- 9194341
TI  - [Studies on mechanism of wasting syndrome in TCDD-intoxicated rats].
AB  - In order to examine a relevance of glucose metabolism and thyroid function in
      TCDD-induced wasting syndrome, an insulin sensitivity assessment with chemical
      analysis of blood plasma were carried out in male Wistar rats exposed orally to
      TCDD. Laboratory findings in plasma showed elevation of glutamic-oxalacetic
      transaminase (GOT) and lipid peroxide value, decrease in thyroxine (T4) with
      increase in triiodothyronine (T3) value, and slight but significant decrease in
      fasting blood glucose and basal insulin level. The glucose disposal rate in
      euglycemic insulin clamp test was significantly elevated. These data suggest that
      TCDD-induced wasting syndrome might relate to the disturbance of glucose
      metabolism of the main organ through insufficiency of caloric intake, T4 and
      insulin.

PMID- 9194342
TI  - [Yearly and seasonal fluctuation of PCB concentration in skin surface lipid].
AB  - PCB concentrations in the skin surface lipids of Yusho patients had been examined
      for 6 years (in July, 1990-1995). The concentrations in each patients showed a
      little fluctuation every year. It suggests that the cutaneous sebaceous system is
      one of the excretory systems of PCB. In 1995, measurement of PCB was performed
      also in October. The mean concentration of PCB was lower than that measured in
      Summer (692.7 ng/g in July versus 633.3 ng/g in October, p < 0.05). To explain
      the fluctuation, seasonal change of sebum composition should be examined.

PMID- 9194343
TI  - [In vitro analysis for cellular toxicity of polychlorinated biphenys (PCBs) on
      HeLa cellular proliferation (IV)--the effect of Kanpo preparations on cellular
      toxicity].
AB  - In this study, we investigated the cell toxicity of polychlorinated biphenys
      (PCBs) as an indicator of the quantity of cellular protein in HeLa cells. Assay
      for protein concentration was performed by Lowry's method using a commercially
      available bovine serum albumin as standard preparation. The reductive action of
      inchinkou-tou, inchinkou, sansisi and daiou on the PCBs toxicity was
      investigated. The relationship of cell number (0-40.000) to protein
      concentrations (0-80 micrograms) was shown R2 = 0.993 (Y = 5.0 x 10(-6) X
      +0.027). The final concentration of these drugs and PCBs was used for 100
      micrograms/ml, respectively. The cellar protein concentration increased to 20%
      with the addition of inchinkou-tou. Inchinkou and sansisi were revealed slightly
      elevation, but daiou was not. These results suggested that inchinkou-tou, kanpou
      preparation, was better effective than constructive crude drugs, but statistical
      evidence could not find.

PMID- 9194344
TI  - [Effects of polychlorinated biphenyls on regenerating myelin of peripheral nerve
      in rats].
AB  - The effects of polychlorinated biphenyls (PCB) on regenerating myelin of the
      peripheral nerves were investigated in rats. The sciatic nerves were crushed at
      the mid-thigh level on the last of 32 days of oral administration of PCB. The
      sciatic nerves were biopsied from the crushed regions at 4, 8 and 12 weeks after
      crushing. The nerves were fixed in 2.5% glutaraldehyde buffered with 0.1 M sodium
      cacodylate and embedded in epon 812. The ultrathin sections were analysed by JEOL
      JEM-1210 with EDAXDX-4. The chloride which was composed of PCB was increased in
      myeline on 4 weeks after crushing. Freeze fracture study of myelines of sciatic
      nerves on 8 and 12 weeks after crushing showed an increase of intramembranous
      particle on 12 weeks and an increase of caveolae on 8 weeks. These results
      suggest that PCB may affect the plasmamembrane of shwann cell and induce the
      disturbance of myeline.

PMID- 9194345
TI  - [Elevation of serum creatine kinase in the patients with Kanemi Yusho].
AB  - 18.9% of the patients with Kanemi Yusho showed an elevation of serum creatine
      kinase, however, the cause is still unknown. The relation between exercise,
      dehydration, thyroid hormone and concentration of PCB was studied. Dehydration,
      hyperexercise and PCB affected the elevation of creatine kinase. No relation
      between PCB and thyroid hormone or creatine kinase and thyroid hormone was
      observed. PCB may change the permeability of muscle plasma membrane.

PMID- 9194346
TI  - [Symptoms and blood PCB level among chronic Yusho patients, twenty-five years
      after outbreak].
AB  - To investigate the frequency of symptoms and signs and their relationships with
      blood PCB (polychlorinated biphenyls) levels, twenty-five years after outbreak,
      we analyzed the data of 276 Yusho patients (male/female: 137/139) who had
      received health examination in 1993. For this purpose, 31 examination items which
      correspond or relate to the diagnostic criteria for Yusho (1976) were selected
      from the examination form. Mean blood PCB concentration in the subjects was 4.69
      ppb with the highest value of 31.0 ppb (median : 4.0 ppb). The symptoms for which
      the proportion exceeded 60% were general fatigue, headache and numbness in
      extremities. Chronic bronchitis-like symptoms, such as cough and sputum, were
      observed in 50% of the subjects. Next, the subjects were classified into
      approximate quartiles of blood PCB: < 3.00, 3.00-4.06, 4.07-5.99, and 6.00+ppb.
      The distributions of subjects at four levels of blood PCBs were compared between
      the groups with or without each symptom or sign, using the Cochran-Mantel
      Haenszel test. Significant differences were observed for comedones in the trunk
      (P = 0.02) and other regions (P = 0.02); acneiform eruptions in the genital
      regions (P = 0.01) and gluteal regions (P = 0.01); and hypersecretion in the
      Meibomian gland (P = 0.04). Thus, the typical skin and eye symptoms in Yusho
      patients still persist showing a close relation with blood PCB concentration.

PMID- 9194347
TI  - [An epidemiologic examination on the prevalence of the periodontal diseases and
      oral pigmentation in Yusho patients in 1996].
AB  - An epidemiologic examination was carried out to reveal the prevalence of the
      periodontal diseases and oral pigmentation in patients with Yusho 28 years after
      PCB exposure. The results obtained were as follows. 1) 162 teeth out of a total
      of 309 examined teeth had a periodontal pocket deeper than 3 mm, although 32
      teeth out of 162 teeth had a periodontal pocket deeper than 4 mm. 2) Oral
      pigmentation was observed in 47 out of 82 patients with Yusho. It was
      particularly noteworthy that gingival pigmentation was observed at a much higher
      frequency in younger patients while pigmentation of the buccal mucosa, the lips
      or the palate was observed at a much higher frequency in older patients.

PMID- 9194348
TI  - [Thyroid function in patients with Yusho: 28 year follow-up study].
AB  - To evaluate chronic effect of polychlorinated biphenyl (PCB) on thyroid
      functions, thyroid hormone levels and thyroidal autoantibodies were studied in 81
      patients with Yusho in 1996. Serum level of thyroid stimulating hormone (TSH) was
      elevated in 7 cases (8.6%). All of them showed normal triiodothyronine (T3),
      thyroxine (T4) and free T4 levels, and regarded as latent hypothyroidism. There
      were no significant correlations between blood PCB concentrations and TSH levels,
      T2 levels, T4 levels or free T4 levels. Thyroglobulin antibodies were detected in
      8 cases (19.5%) of 41 Yusho patients with high PBC concentration (higher than 3.0
      ppb), and in only one case (2.5%) of 40 patients with low PBC concentration
      (lower than 2.9 ppb). We conclude that thyroglobulin antibody in patients with
      Yusho is not frequent and it may be associated with blood PCB concentration.

PMID- 9194350
TI  - Introduction to the EUR-ASSESS Report.

PMID- 9194349
TI  - [Dermatological findings in the annual examination of the patients with Yusho in
      1995-1996].
AB  - We reported the grades of severity of skin symptoms and the blood PCB patterns
      and concentrations in Yusho patients who had the annual examinations in 1995 and
      1996. The skin severity grades and the skin severity scores showed the same
      tendency as recorded in the last 10 years. Yusho patients who were scored as more
      than 6.7 were around 8% of the total patients both in 1995 and 1996. The
      correlation between the blood PCB patterns and the severity grades of skin
      symptoms was clear. Thus, the mean skin severity scores in patients showing A
      pattern were higher than those in patients showing either B or C pattern. The
      same results were obtained when the correlation between the blood PCB patterns
      and the skin severity grades was analyzed. Patients whose ages were 50-70 years
      old were found to show the highest blood PCB concentrations and the skin severity
      scores.

PMID- 9194351
TI  - Priority setting for health technology assessment. Theoretical considerations and
      practical approaches. Priority setting Subgroup of the EUR-ASSESS Project.

PMID- 9194352
TI  - EUR-ASSESS Project Subgroup report on Methodology. Methodological guidance for
      the conduct of health technology assessment.

PMID- 9194353
TI  - EUR-ASSESS Project Subgroup Report on Dissemination and Impact.

PMID- 9194354
TI  - EUR-ASSESS Project Subgroup Report on Coverage.

PMID- 9194355
TI  - Selecting the best renal function tests. A meta-analysis of diagnostic studies.
AB  - A literature review compared the results of different kidney function tests using
      the inulin clearance or similar methods as a gold standard. The methodological
      strength of the available studies was weak. For the time being, the calculated
      creatinine clearance using formula, is a first choice, especially in general
      practice.

PMID- 9194356
TI  - The effects of health insurance on access to new medical technologies.
AB  - We examined the use of percutaneous transluminal coronary angioplasty, kidney
      stone lithotripsy, and bone marrow transplant among patients with different
      health insurance plans in California. HMO enrollees were less likely to receive
      these procedures compared with fee-for-service patients. Our results have
      implications for the inflationary effects of technology under managed care.

PMID- 9194357
TI  - Laparoscopically assisted vaginal hysterectomy. A review of current issues.
AB  - A review of 39 articles found no consensus on indication for laparoscopic
      assisted vaginal hysterectomy (LAVH) compared with traditional approaches. Since
      only three randomized trials comparing LAVH with traditional methods exist, the
      scientific basis for surgical choice is lacking. Uncontrolled studies indicated
      that outcomes following LAVH were not superior to vaginal hysterectomy and costs
      were significantly higher.

PMID- 9194358
TI  - Evaluating the impact of health care information systems.
AB  - Evaluating the impact of computer-based medical information systems requires not
      only an understanding of computer technology but also an understanding of complex
      social and behavioral processes. This essay discusses the need for evaluation of
      health care information systems, a set of evaluation questions based on
      assumptions about the impact of technology on organizations, and recommendations
      for reducing barriers to the implementation of health care information systems.

PMID- 9194359
TI  - [Radiological anatomy of the vein of Labbe].
AB  - The development and radiology of the vein of Labbe (VL) were investigated using
      the brains of 19 aborted human fetuses and 6 normal adults injected at autopsy
      with radiopaque material through the venous system. Carotid angiograms taken in
      stereoscopic pairs (110 cases, 167 hemispheres) were also analyzed in detail.
      Developmental alterations of the cerebral structures, particularly those of the
      opercula and cerebral sulci, are reflected in our classification of the pial
      veins of the lateral cerebral convexity into the superior, middle and inferior
      groups. The anastomotic veins of Trolard and Labbe were already recognizable at
      the fetal age of 6 to 7 months, as development of the opercula and resultant
      depression of the insula became advanced. In our series, superficial draining
      veins opening into the VL were 14 to 20 mm (average 16.8 mm) in length.
      Anastomoses among the superior, middle and inferior groups were analyzed
      angiographically: single anastomosis was found in 23 percent of cases, while
      double and triple anastomoses were found in 32 and 45 percent, respectively. A
      majority of the veins at the sites of anastomosis were found to have calibers of
      less than 1 mm. The VL, therefore, should be considered in most cases as an
      independent major superficial draining venous channel of the cerebral convexity
      with insignificant connections with the superior and middle groups.

PMID- 9194360
TI  - [Basic and clinical studies of oral barium sulfate preparations for CT].
AB  - In CT examination of the abdomen and pelvis, oral iodinated contrast agents and
      oral barium sulfate preparations are now being used to improve diagnostic
      accuracy, and studies have been carried out on their clinical usefulness.
      Although helical CT has come into wide spread use recently, most studies have
      used the ordinary type of CT. There have been no reports on studies using barium
      sulfate preparations with helical CT. We, therefore, prepared several barium
      sulfate preparations with different concentrations and particle diameters, and
      conducted a basic study to determine the optimal conditions for helical CT. In
      addition, we conducted a similar study using the ordinary imaging method for
      comparison with helical CT. Based on the results of these studies, we conducted a
      clinical study with several volunteers to find the most suitable barium sulfate
      preparation. Our basic study compared Baritop CT and Gastrografin, and a
      concentration of 1.5%-2.0% was found suitable. In our examination of particle
      size using animal intestines, fine particles were found to be most appropriate.
      Although little difference was observed between the helical procedure and the
      ordinary imaging procedure, the possible development of artifacts specific to the
      helical procedure was suggested. In the clinical study, the 2.0% preparation
      tended to show better contrast and a better filling rate for the upper abdominal
      organs than the 1.5% preparation. However, little difference in artifacts was
      found between them. The artifacts tended to be intensified when barium migrated
      toward the distal portion of the small intestine. Judging from these results, a
      2.0% fine particle preparation appeared to be suitable for examination of the
      upper abdominal organs. For organs in the pelvic region, preparations with a
      lower concentration were considered suitable.

PMID- 9194361
TI  - [Fast cine MR coronary angiography compared with conventional coronary
      angiography: criteria for coronary artery stenosis].
AB  - Magnetic resonance coronary angiography (MRA) was performed in 5 healthy
      volunteers and 13 patients to evaluate its diagnostic capability. Ten to 15
      continuous cross sections were obtained for each coronary artery using fast
      cardiac cine MR (FASTCARD) with breath-hold, and reconstructed images were made.
      The control study showed good demonstration of the left main, proximal left
      anterior descending (Seg. 6) and proximal right (Seg. 1, 2) coronary arteries.
      Abnormal findings were classified as interruption, stenosis (severe or mild),
      irregularity, or decreased signal, and they were compared with the findings of
      conventional angiography in proximal segments (Seg. 1,2,5,6). Twelve of 15
      lesions with significant stenosis (> 75%) were depicted as interruption or severe
      stenosis (sensitivity 80%). The sensitivity was 100% (6 of 6 lesions) in the
      right coronary artery and 67% (6 of 9 lesions) in the left coronary artery. The
      positive predictive value was 75% (12 of 16). Comparison at each segment revealed
      that the sensitivity, specificity and accuracy for interruption or severe
      stenosis were 92%, 79%, and 86%, respectively, for severe stenosis (> 90%), and
      85%, 79%, and 83% for significant stenosis (> 75%). Interruption or severe
      stenosis on MRA is presumed to be an appropriate criterion for the detection of
      significant stenosis in the proximal coronary artery.

PMID- 9194362
TI  - [Scanning electron microscopic studies on mucosal coating by barium mixtures].
AB  - The purpose of this study was to observe and evaluate mucosal coating by barium
      mixtures using electron microscopy. Specimens from the ileum of two pigs, about
      50cm in length from the terminal ileum, were divided into 3 groups with different
      in concentrations and additives of barium mixture. The 50cm length of ileum was
      cut into 10cm long pieces. Four specimens from each group were evaluated by
      double contrast study for coating by the barium layer. Then the specimen was
      frozen with liquid nitrogen solution, and fixed. Afterward, the specimen was cut
      into about 1cm sections, fixed again, dehydrated, dried, and observed by scanning
      electron microscopy (SM). In the double contrast study, the differences in barium
      coating were correlated with the concentration of barium sulphate. The scanning
      electron microscopic findings were correlated with those of the double contrast
      study. The various additives in the barium mixture did not cause any distinctive
      differences. Although barium particles have been studied by electron microscopy,
      barium mixture coating state on the mucosa of biological materials has not been
      reported. In conclusion, a correlation of the coated barium layer on double
      contrast study and the images of scanning electron microscopy was observed using
      pig ileum specimens.

PMID- 9194363
TI  - [High-dose conformal radiotherapy for glioblastoma multiforme].
AB  - The purpose of this study was to evaluate the impact of administering high doses
      by rotational multi-leaf collimator (MLC) conformal radiation therapy. From 1984
      to 1995, thirty-five consecutive cases with glioblastoma multiforme were treated
      using rotational MLC conformal therapy. There were 23 men and 12 women, with an
      average age of 45 years (12-73 years). Median Karnofsky performance score was
      80(30-100). Median tumor volume was 56 cc (8-800 cc). All patients underwent
      surgical intervention (only biopsy in one, partial resection in 13, subtotal
      resection in 18, and gross total resection in three). Radiation dose ranged from
      60 to 80 Gy (mean 68.5 Gy) in 21 patients treated before 1991, and was 90 Gy in
      the 14 patients treated thereafter. Biweekly intravenous chemotherapy was also
      administered in both arms. The 1-year, 2-year, and 5-year survival rates were
      72%, 43%, and 21%, respectively. Residual tumor volume was the only statistically
      significant factor for survival by multivariable analysis. The five-year survival
      rate of patients with residual tumors 2 cm or less in diameter was as high as
      44%. Local failure was observed in 15 of the 18 patients in the lower dose group,
      whereas it was observed in only 4 of the 10 patients in the higher dose group.
      The difference was statistically significant. Rotational conformal therapy in
      combination with intensive surgical resection showed a favorable outcome.
      However, increased dose did not lead to higher survival rate.

PMID- 9194364
TI  - [Radiation therapy for low-grade astrocytomas: survival and QOL].
AB  - From 1980 to 1994, 59 patients with a diagnosis of lowgrade astrocytoma were
      treated in our hospital. We analyzed survival, prognostic factors and quality of
      life (QOL) in survivors who had been recurrence free for at least 2 years. The
      overall 2-, 5- and 10-year survival rates were 75, 65 and 49 % respectively. The
      major prognostic factors were field size (the smaller, the better) and age (the
      younger, the better) according to Cox regression analysis. Quality of life was
      evaluated in the 20 patients who had survived at least 2 years without tumor
      regrowth. Performance status was good in most of the patients, and 17(85%)
      patients were intellectually and physically normal. Headache, fatigue and memory
      difficulties were the major clinical complaints of these patients and were
      observed in 7(35%), 6(30%) and 7(35%) of the patients, respectively, although
      severe symptoms were rare.

PMID- 9194365
TI  - [Balloon-occluded intraarterial infusion therapy for advanced uterine cervical
      cancer: usefulness of four-lumen double balloon catheter].
AB  - We have devised a new catheter with four-lumen and a double balloon (4L-DB),
      which has made it easy to find feeding arteries and enhanced the local
      concentration of drugs. At first, two 4L-DB catheters were inserted into the
      contralateral internal iliac artery, via the bilateral femoral arteries. Then,
      the distal balloon was set in the superior gluteal artery and the proximal
      balloon in the internal iliac artery. Between the two inflated balloons, anti
      cancer drugs (CDDP 100mg, Therarubicin 20mg, MMC 20mg) were infused to the
      bilateral uterine arteries during 30 minutes via side holes. The response rate
      for this therapy was 71%, and 3 cases of complete response (CR) were obtained. No
      severe side effects were observed. In conclusion, the 4L-DB catheter may be an
      exceedingly efficient method of local anticancer drug infusion.

PMID- 9194366
TI  - [Enhanced 3D subtraction MR angiography of head and neck tumors].
AB  - Contrast-enhanced three-dimensional MR angiography (MRA) combined with a
      subtraction technique was performed in six patients with a solid tumors in the
      head or neck region. Using the subtraction technique, the contrast-to-noise ratio
      between the internal carotid artery and fat tissue increased from 18.2 +/- 7.4 to
      64.7 +/- 30.8. The MRA findings demonstrated both arteries and enhancing tumors
      with effective background signal suppression, making tumor extension and relation
      to the arterial branches more evident. The proposed technique is promising for
      screening arterial abnormalities of the head and neck in patients with solid
      tumors.

PMID- 9194367
TI  - [Highly reproducible technique for the estimation of trabecular bone density:
      three slice method on peripheral quantitative CT].
AB  - The reproducibility of bone mineral density (BMD) measurements with peripheral
      quantitative CT has been limited by the repositioning error. In this study, 1 mm
      step 3-slice scan data were used to compensate for this error in trabecular BMD
      of the distal radius. The assessment was based on the liner relations between the
      cross-sectional area and trabecular bone mineral content and trabecular area
      ratio, on the condition that the trabecular bone is defined by a BMD value. The
      estimated reproducible errors of less than 2% under clinical conditions indicate
      that the method is reliable for follow-up examination.

PMID- 9194368
TI  - [Transverse relaxation time of metabolites by proton MRS: one of the parameters
      concerned with quantification].
AB  - We examined the transverse relaxation time of metabolites observed by proton MRS
      at 6 different points of TE(18, 30, 60, 90, 135, and 270ms). The double
      exponential curve was better fitted to the 6 points than the single exponential
      curve for calculating the T2 values of the three major metabolites. We considered
      that these metabolites would have a long T2 component and short T2 component, and
      the correct T2 value is difficult to obtain under the limitations of measurement
      time available in clinical applications.

PMID- 9194369
TI  - [Construction of an MRI reporting system using the Internet].
AB  - Out university hospital, includes a LAN (Local Area Network) and uses network
      services such as WWW(World Wide Web). We have constructed an MRI diagnostic
      reporting system on the Internet in which interactive date management was
      established on WWW by using CGI (Common Gateway Interface) software. Linking
      database information such as MRI reports with WWW browsers using by CGI provides
      easy data access to the database and offers hypertext and searching. This system
      suggests the possibility of creating a cheaper and more flexible network using
      Internet technology.

PMID- 9194370
TI  - [Asymptomatic cerebrovascular disorders: diagnosis and management].

PMID- 9194371
TI  - [Bone marrow MRI in hematological disorders].

PMID- 9194372
TI  - [Bone marrow transplants from unrelated donors].

PMID- 9194373
TI  - [The biology of apoptosis].

PMID- 9194374
TI  - [Hematopoietic factors: serum concentrations and clinical application].

PMID- 9194375
TI  - [Treatment with erythropoietin (EPO) of the anemia of patients with hematological
      diseases].

PMID- 9194376
TI  - [The use of G-CSF in hematological disorders].

PMID- 9194377
TI  - [Late effects of treatment with recombinant human granulocyte colony-stimulating
      factor in patients with aplastic anemia].

PMID- 9194378
TI  - [Clinical application of M-CSF on AML patients].

PMID- 9194379
TI  - [Brief history and future prospects of treatment of childhood acute lymphocytic
      leukemia].

PMID- 9194380
TI  - [Treatment of acute lymphoblastic leukemia in adults: a review of 10 year study
      of Japan Adult Leukemia Study Group].

PMID- 9194381
TI  - [Cell surface markers and treatment results in childhood acute lymphoblastic
      leukemia (ALL)].

PMID- 9194382
TI  - [Treatment and immunophenotype of acute lymphoblastic leukemia].

PMID- 9194383
TI  - [Correlation between treatment outcome and cytogenetic and molecular findings in
      childhood acute lymphoblastic leukemia].

PMID- 9194384
TI  - [The correlation between alterations of cell cycle-regulating, tumor-suppressor
      genes and the clinical prognosis in adult ALL patients].

PMID- 9194385
TI  - [Role of bone marrow transplantation for high risk acute lymphoblastic leukemia
      in children].

PMID- 9194386
TI  - [Philadelphia chromosome (BCR/ABL)--positive acute lymphoblastic leukemia:
      clinical characteristics and prognostic analysis for the effective therapeutic
      strategy].

PMID- 9194387
TI  - [Autologous BMT for B-lineage adult ALL patients using ex vivo purging with
      monoclonal antibodies].

PMID- 9194388
TI  - [A study on antiprothrombin antibodies in antiphospholipid syndrome].
AB  - In this study we investigated the frequency and the type of manifestations of
      antiprothrombin antibodies (aFII) in patients with antiphospholipid syndrome
      (APS). In 16 (84.2%) of 19 patients with lupus anticoagulant (LA) and either
      anticardiolipin antibodies or antiphosphatidylserine antibodies, two types of
      abnormal patterns were shown on a crossed immuno-electrophoresis technique using
      anti-human prothrombin murine IgG. The slow-moving peak of prothrombin was
      detected in 8 patients, while a peak in the other patients had the slow-moving
      shoulder. These slow-moving materials might represent prothrombin-aFII complexes.
      In 13 patients who were studied on Western blots, IgGs of 11 patients (84. 6%)
      bound to human purified prothrombin, and the IgGs of 7 (53.8%) of these patients
      also bound to human purified alpha-thrombin. Our results indicate that aFII
      detected in patients with APS may explain part of the mechanism of LA.

PMID- 9194389
TI  - [Two-peak monoclonal protein (IgA kappa and IgG kappa) in non-Hodgkin lymphoma].
AB  - A 72-year-old man was admitted because of general weakness. On physical
      examination, marked splenomegaly was found. Blood tests revealed anemia,
      thrombocytopenia and two-peak hypergammaglobulinemia composed of kappa type IgG
      and IgA monoclonal proteins. Peripheral blood and bone marrow (BM) contained
      abnormal lymphocytes including plasmacytoid lymphocytes and/or plasma cells.
      Pathological examination of the biopsied BM showed non-Hodgkin lymphoma
      consistent with the lymphoplasmacytoid type. Immunohistochemical staining
      revealed two different populations of cells, one with IgG and the other with IgA;
      no cell stained both and no solitary cluster of either IgG or IgA positive cell
      was seen. The surface phenotype of the lymphoma cells was CD19+, CD20+, HLADR+.
      Double immunofluorescence staining of the BM smear showed IgG or IgA positive
      plasma cells, whereas small lymphocytes were negative for IgG and IgA. Analysis
      of immunoglobulin genes in the BM cells showed 2 rearranged bands in each of
      heavy chain genes and kappa light chain genes. The patient was treated with
      modified MVCP therapy and the two monoclonal proteins decreased in parallel with
      the improvement of splenomegaly. These findings strongly suggest that the two
      peak monoclonal protein was produced by monoclonal lymphoma cells. The patients
      has been disease-free without any therapy since August, 1995.

PMID- 9194390
TI  - [All-trans retinoic acid-induced myelomonocytoid differentiation in acute
      promyelocytic leukemia].
AB  - A 30-year-old man with a diagnosis of acute promyelocytic leukemia (APL) was
      admitted. Laboratory findings were as follows: WBC 32,900/microliter with 88%
      promyelocytes, Hb 10.4 g/dl, platelets 2.6 x 10(4)/microliter. Coagulation tests
      revealed DIC. Bone marrow was hypercellular with 91.8% promyelocytes which were
      strongly positive for peroxidase and positive for alpha-naphthyl butyrate
      esterase. Cytogenetic study revealed 46, XY, t(15;17) (q22:q11). He was treated
      with all-trans retinoic acid (ATRA) along with hydroxyurea (HU) and low-molecular
      weight heparin (LMH). Because his WBC increased to 93,700/microliter on day 6 of
      ATRA therapy, DCMP chemotherapy was given, while ATRA was withheld. He developed
      enterocolitis due to myelosuppression. ATRA was restarted along with granulocyte
      colony stimulating factor (G-CSF). His WBC rose to 10,400/microliter with a
      marked, but temporary predominance of myelomonocytes both in peripheral blood and
      in bone marrow. These myelomonocytoid cells were positive for specific and
      nonspecific esterase double stainings. Then he entered complete remission. It was
      of interest that myelomonocytoid differentiation of APL cells was induced by
      ATRA. The etiology was discussed.

PMID- 9194391
TI  - [Essential thrombocythemia in transformation to acute leukemia (FAB-M0) as a
      natural history from myelofibrosis with t(1;7)].
AB  - A 34-year-old man was found to have leukocytosis and thrombocytosis in 1983. In
      1988, his leukocyte count was 10,400/microliter, Hb 16.5g and a platelet was 73 x
      10(4)/microliter. A bone marrow examination showed megakaryocyte hyperplasia.
      Essential thrombocythemia (ET) was diagnosed but no treatment was given. In
      February 1993, anemia and hepatosplenomegaly developed and cytogenetic study of
      the peripheral blood demonstrated t(1;7) (q10;p10). Myelofibrosis was diagnosed
      as by bone marrow biopsy. The patient was treated with blood transfusion,
      oxymetholone and prednisolone, but without effect. In 1995, acute myeloid
      leukemia developed, and he died in December 1995 due to septicemia. We report
      here a case of the ET developed myelofibrosis with t(1;7) (q10;p10) anomaly and
      acute leukemia.

PMID- 9194392
TI  - [The disturbance of reversible operation in space in the early stage of
      Alzheimer's disease].
AB  - Constructional apraxia is one of the neuropsychological findings frequently
      observed in the early stage of the Alzheimer's disease, which may result from the
      visuo-spatial disturbances. The visual space consists of a variety of visual
      information processing, viewer-centered coordinate system, objects-centered
      coordinate system, integration of both coordinate systems, and verifying visual
      representation with the knowledge in the memory. The reversible operation in
      space, or mental rotation appears to play an important role in visuo-spatial
      functions, which refers to the operation of the visual representation at one
      orientation in viewer-centered coordinate system to construct the representation
      in object-centered coordinate system so that one can look like if it were
      presented at another orientation. To the present, little is known about
      reversible operation or mental rotation in patients with Alzheimer's disease. In
      this present paper, we attempted to investigate the ability of reversible
      operations in space so as to understand the mechanisms underlying constructional
      apraxia, or visuo-spatial disturbances in the early stage of Alzheimer's disease.
      The subjects were 12 patients with Alzheimer's disease in early stage (AD group),
      12 patients with multi-infarcts dementia as disease control (MID group), 12 age
      matched persons as healthy control (HC group). In perspective taking tasks, that
      requires the subjects to imagine the spatial arrangement of the objects at the
      different view points from the subjects' one, AD group showed more severe
      deficits than MID group and HC group. Moreover, in a task that the subjects were
      asked to assume the photo-angle of the photograph taken of the model which was in
      front of them, AD group was imparied compared to the control groups. These
      disturbances were closely associated with deficits in Block Design test of WAIS.
      These results clearly demonstrate that the patients with Alzheimer's disease have
      disturbance in reversible operation in space and that the disturbance may be
      responsible for visuo-spatial dysfunctions, not only the constructional apraxia,
      but also a variety of performance deficits in the early stage of Alzheimer's
      disease.

PMID- 9194393
TI  - [Clinical study of prejudicing autochthonous speech act (thought)--acceleration
      of the activity in the remission process of schizophrenia].
AB  - Schizophrenics occasionally experience guilty feeling at having insulted someone
      such as having said "You fool" or "Die" to a new acquaintance. They also
      experience guilty feeling from autochthonous thought, a feeling of having
      prejudiced his neighbour. This latter autochthonous thought is considered to be
      closely related with the former prejudicing speech act. The author would
      provisionally call these phenomenons of prejudice, prejudicing autochthonous
      speech act (or prejudicing autochthonous thought), particularly in the case in
      which the object of prejudice is an intimate real other, or a co-presenting
      other. Based on his own nine cases, the author has first described the clinical
      characteristics of this symptom, and then developed psychopathological
      considerations to draw a attention to the therapeutic importance of this symptom.
      On the symptomatological ground, the prejudicing autochthonous speech act
      (thought) belongs to psychomotor verbal hallucinations (J. Seglas), more
      precisely to the soliloquy type of this hallucination. On the clinical ground,
      this symptom is likely to follow auditory hallucination caused by an acute state
      or that of recovery period from this state. Furthermore, it is not infrequent
      that general improvement as well as remission follow the appearance of this
      symptom. This symptomatological change of the center of gravity, that is, the
      gradual transition from auditory hallucination to prejudicing autochthonous
      speech act (thought) is considered to correspond to a change of the patient's
      position in relation to others. This position, once experienced passively, is now
      experienced actively. In other words, the patient, coming out of an acute
      psychotic state and opening to an intersubjective world, is confronted with a
      high tension relationship with others. The prejudicing autochthonous speech act
      (thought) appears in this situation, to restore the patient's own subjectivity in
      coping with the pressure of real others. In this case, this phenomenon is
      considered to have a selfhealing effect. Prejudicing autochthonous speech act
      (thought), presents not only a certain disappearance process of auditory
      hallucinations, but also a kind of acceleration of the patient's activity in the
      preremission period which leads to a remission. Prejudicing autochthonous speech
      act (thought) should be therefore considered in the therapy of schizophrenics.

PMID- 9194394
TI  - [Molecular action mechanisms and membrane recognition of membrane-acting
      antimicrobial peptides].
AB  - A number of antimicrobial peptides have been isolated in the animal kingdom,
      serving as defensive or offensive weapons. The mechanisms of their action are
      considered to be the permeability of bacterial membranes, although the details
      are not yet clarified. I have studied the interactions of several antibiotic
      peptides with both artificial lipid bilayers and biomembranes to elucidate the
      molecular mechanisms of the action and to find out the rationale for their
      membrane specificity. Magainin 2 from the Xenopus skin was found to form a
      peptide-lipid supramolecular complex pore in the membrane, followed by peptide
      internalization, simultaneously dissipating the transmembrane potential and the
      lipid asymmetry. This novel mechanism also works for a wasp bee venom, mastoparan
      X. Tachyplesin I from Tachypleus and a bee venom, melittin, also translocate
      across the membrane by forming a pore. The membrane selectivity of these peptides
      is closely related to their affinity for the lipids constituting the membrane
      surface. A strategy for developing a potent antibiotic was discussed based on
      these results.

PMID- 9194395
TI  - [Development of analytical technologies for human genomic DNA using capillary
      electrophoresis and their applications].
AB  - Capillary electrophoretic systems equipped with a multi-color detectable laser
      induced fluorescent DNA detector (CE-LIF) were developed. We examined the
      efficiency and the performance of the CE-LIF systems for the high-speed DNA
      sequencing and DNA diagnosis for human diseases. The effect of the gel
      composition, electric field strength, and capillary length on the separation of
      DNA sequencing reaction product was investigated in order to achieve high-speed
      DNA sequencing for large-scale sequencing in the Human Genome Project. The CE-LIF
      system is successfully applied to ultrafast cDNA sequencing for human and yeast
      genomes. Under optimum separation conditions, only 10 min is required to sequence
      300 base DNA. A polymer solution of cellulose derivative was utilized as a
      sieving medium for the CE-LIF system and gave excellent resolution of polymerase
      chain reaction (PCR) amplified polymorphic loci on the human genome. The CE-LIF
      system is successfully applied to the DNA diagnosis for cancers through CA repeat
      analysis of human D8S 1218 locus, heart diseases through VNTR (variable number of
      tandem repeat) analysis of human apolipoprotein B gene and Alzheimer's disease
      through RFLP (restriction fragment length polymorphism) analysis of human
      apolipoprotein E gene with high-speed and high resolution. Capillary affinity gel
      electrophoresis was developed as a new technique for the recognition of the
      specific DNA base and/or sequence. This technology is also applicable to the
      characterization of binding properties of DNA based drugs. The principle, the
      theory, and the methods of capillary affinity gel electrophoresis are presented.
      This technique is applied to the determination of association constants between
      an affinity ligand and oligonucleotides. The great potential of capillary
      affinity gel electrophoresis for the detection of the mutation on DNA is
      illustrated.

PMID- 9194396
TI  - [Some recent advances in Pummerer-type reactions].
AB  - The Pummerer rearrangement of sulfoxides with acid anhydrides is a useful method
      for the synthesis of alpha-substituted sulfides and has attracted considerable
      attention from both synthetic and mechanistic points of view. In recent years, we
      have developed two novel and significant Pummerer-type reactions; i) an
      asymmetric Pummerer-type reaction of chiral, non-racemic sulfoxides with a highly
      enantiomeric excess, and ii) the first successful Pummerer-type reaction of the
      aromatic ring. In this review, we describe 1) the asymmetric Pummerer-type
      rearrangement induced by an O-silylated ketene acetal, 2) the asymmetric Pummerer
      type rearrangement induced by an ethoxy vinyl acetate, 3) the additive-Pummerer
      type reaction, 4) the asymmetric Pummerer-type cyclization induced by an O
      silylated ketene acetal, and 5) the aromatic Pummerer-type reaction of p-sulfinyl
      phenol derivatives leading to peri-hydroxy dihydroquinone derivatives.

PMID- 9194397
TI  - [Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene
      D4 of benzenesulfonamide derivatives].
AB  - In order to find dual antagonists against both thromboxane A2 (TXA2) and
      leukotriene D4 (LTD4) receptors for a new antiasthmatic agent, various
      benzenesulfonamide derivatives were synthesized and evaluated for those
      pharmacological effects. TXA2 and LTD4 antagonistic activities in vitro were
      evaluated by the inhibitory effects on LTD4-induced and U-46619-induced
      contraction of guinea-pig trachea. Furthermore, TXA2 and LTD4 antagonistic
      activities in vivo were evaluated by the inhibitory effects on LTD4-induced and U
      46619-induced bronchoconstriction of guinea-pig after oral administration of test
      compounds. It was found that 4-[5-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]
      2-thi eny l]butyric acid and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methyl-hexyl]
      2-thienyl]but yric acid possess good anti-LTD4 and anti-TXA2 activities by oral
      administration.

PMID- 9194398
TI  - Amanita phalloides mushroom poisoning--Northern California, January 1997.

PMID- 9194399
TI  - Toxic shock syndrome--United States. 1980.

PMID- 9194400
TI  - Work-related aviation fatalities--Alaska, 1990-1994.

PMID- 9194401
TI  - Prevalence of aspirin use to prevent heart disease--Wisconsin, 1991, and
      Michigan, 1994.

PMID- 9194402
TI  - Suicide--Washington, 1980-1995.

PMID- 9194403
TI  - Toxigenic Corynebacterium diphtheriae--Northern Plains Indian Community, August
      October 1996.

PMID- 9194404
TI  - Effect of chelation with meso-dimercaptosuccinic acid (DMSA) before and after the
      appearance of lead-induced neurotoxicity in the rat.
AB  - This paper examines whether a chelating agent (DMSA) can prevent and reverse the
      effects of lead (Pb) as evidenced by changes in brain glial fibrillary acidic
      protein (GFAP) concentration and in the habituation pattern of rearing behavior.
      Male F344 rats (42 days old) received Pb acetate at 150 or 2000 ppm as Pb in
      their drinking water for 21 days and returned to regular water for another 21
      days to observe recovery. Blood Pb (BPb) concentration rose to 37 and 82
      microg/dl for 150 and 2000 ppm, respectively. Rats exposed to 150 ppm Pb
      exhibited changes in GFAP concentration and behavioral hyperactivity, when placed
      in an unfamiliar cage. The 2000 ppm Pb exposure caused greater changes in GFAP,
      but behavioral hyperactivity appeared only postexposure, when BPb was declining.
      Chelation (DMSA, 50 mg/kg po, 3 times/week for 21 days) decreased the BPb
      concentration, and prevented and reversed the Pb-induced changes in GFAP and
      rearing, but not in body weight. Administration of DMSA by itself for 21 days
      caused no untoward effects in brain GFAP, behavior, or body weight. Concurrent
      administration of DMSA and Pb resulted in no evidence of additive toxicity.
      Results indicate that: (1) A brief behavioral test of habituation is a sensitive
      index of neurotoxicity and chelating therapy; (2) Pb-induced hyperactivity
      depends upon BPb concentration regardless of whether activity is measured during
      or after exposure; (3) repeated treatment with DMSA is effective in reducing Pb
      neurotoxicity; (4) there was no evidence that DMSA enhanced the absorption of Pb.
      The finding that DMSA administered late in exposure can hasten the recovery of
      toxic signs suggests that extracellular Pb continues to play a significant role
      even after toxic signs have appeared.

PMID- 9194405
TI  - Altered sensitivity of posttranslationally modified microtubules to methylmercury
      in differentiating embryonal carcinoma-derived neurons.
AB  - The effects of methylmercury (MeHg) on microtubules (MTs) in differentiating
      neurons derived from retinoic acid-induced embryonal carcinoma (EC) cells in
      culture were examined by immunofluorescence microscopy. Undifferentiated EC cells
      contained mostly kinetically labile tyrosinated (TYR) MTs which extended from the
      centrosome and a small population of stable acetylated (ACT) MTs usually (but not
      exclusively) associated with the centrosome. TYR MTs of undifferentiated cells
      underwent concentration- and time-dependent disassembly upon exposure to low
      concentrations of MeHg (1-2 microM), whereas ACT MTs were resistant to MeHg at
      low concentrations, with many remaining intact even in 5 microM MeHg. After 2
      days in retinoic acid the appearance of short neuritic processes was indicative
      of early differentiation. TYR MTs predominated both in the short neurites and
      cell soma and remained susceptible to low concentrations of MeHg. ACT MTs also
      extended into the short neurites but were most often found in small bundles
      within the perikarya. ACT MTs remained more resistant to MeHg than TYR MTs. The
      neuron-specific tubulin isotype betaIII was first detected during the second day
      of differentiation. MTs labeled with antibodies to betaIII showed similar
      sensitivity to MeHg as TYR MTs, suggesting that MTs containing betaIII were
      largely tyrosinated. After 4 and 6 days of differentiation a greater number of
      betaIII-positive neurons were present with progressively longer and often
      branching neurites. TYR MTs were present in cell soma and neurites while ACT MTs
      were found almost exclusively in neurites. TYR MTs remained highly susceptible to
      MeHg (most notably in perikarya) in comparison to ACT MTs at all stages of
      differentiation; however, with increasing time in culture, even TYR MTs gained
      appreciable stability to MeHg. These data indicate that microtubules in
      developing neurons become progressively more resistant to disassembly by MeHg,
      suggesting that the most critical period of MT susceptibility occurs very early
      in development in vivo.

PMID- 9194406
TI  - Toxicity of cadmium in human trophoblast cells (JAr choriocarcinoma): role of
      calmodulin and the calmodulin inhibitor, zaldaride maleate.
AB  - Cadmium (Cd), the heavy metal, is toxic to the placenta. The objectives of this
      study were to determine if Cd toxicity is due to inhibition of placental or
      trophoblast cell proliferation through interactions with the intracellular
      calcium binding protein, calmodulin (CaM). Cd can replace calcium and thus
      interfere with CaM's function. Also, CaM inhibitors reverse selected toxic
      effects of Cd. The CaM inhibitor, zaldaride maleate, was used to determine if Cd
      inhibits trophoblast cell proliferation through interactions with CaM. JAr
      choriocarcinoma cells, a neoplastic trophoblast cell line which is similar to
      early human trophoblast cells, were selected to study this question. Cd (20 and
      40 microM) inhibits JAr cell proliferation, as measured by cell number and BrdU
      incorporation. Zaldaride (10 and 20 microM) inhibits proliferation to a lesser
      extent; 100 microM is lethal. To determine if zaldaride alters actions of Cd,
      zaldaride and Cd are added simultaneously. Zaldaride (20 microM) and Cd (20
      microM) together inhibit proliferation less than Cd alone, thus partially
      protecting cells. Metallothionein is induced in cells exposed to Cd, while
      zaldaride does not cause induction of this cellular defense mechanism protein. To
      determine if Cd inhibits proliferation through alterations of cell cycle, JAr
      cells enriched for G0/G1 phase were exposed to 20 microM Cd, 20 microM zaldaride,
      or 20 microM Cd plus 20 microM zaldaride for 24 hr. Cells remain in G0/G1
      following Cd exposure; cells treated with 20 microM zaldaride progress through S
      phase and into G2. Zaldaride and Cd together allow JAr cells to leave G1 and
      enter S phase, partially relieving the cycle block produced by Cd. This study
      demonstrates a role for calmodulin in mediating the toxicity of Cd in trophoblast
      cell proliferation.

PMID- 9194407
TI  - Differences in phenotype and cell replicative behavior of hepatic tumors induced
      by dichloroacetate (DCA) and trichloroacetate (TCA).
AB  - Dichloroacetate (DCA) and trichloroacetate (TCA) are two hepatocarcinogenic by
      products of water chlorination. To compare the effects of DCA and TCA on cell
      replication in the nodules and tumors they induce, male B6C3F1 mice were
      administered 2.0 g/L DCA or TCA in their drinking water for 38 or 50 weeks,
      respectively. The pretreated mice were then given water containing 0, 0.02, 0.5,
      1.0, or 2.0 g/L DCA or TCA for two additional weeks to determine whether cell
      proliferation in the normal liver or tumors that had been induced by DCA or TCA
      was dependent on continued treatment. Prior to sacrifice the mice were
      subcutaneously implanted with mini-osmotic pumps to label DNA in dividing cells
      with 5-bromo-2'-deoxyuridine (BrdU). Serial sections of nodules/tumors and normal
      liver were stained immunohistochemically for BrdU, the oncoproteins c-Jun and c
      Fos, and hematoxylin and eosin (H & E); or with Periodic acid-Schiff (PAS) stain,
      BrdU, and H & E, respectively. DCA and TCA transiently stimulated the division of
      normal hepatocytes relative to rates observed in the livers of control mice.
      However, at 40 and 52 weeks of treatment, replication of normal hepatocytes was
      substantially inhibited by DCA and TCA, respectively. Cell division within DCA
      induced lesions that were identified macroscopically was significantly higher
      with increasing dose of DCA administered in the last 2 weeks of the experiment.
      DCA-induced lesions were found to display immunoreactivity to anti-c-Jun and anti
      c-Fos antibodies, were predominantly basophilic, and contained very little
      glycogen relative to surrounding hepatocytes. In contrast, rates of cell division
      within TCA-induced altered hepatic foci and tumors were very high and appeared to
      be independent of continued treatment. TCA-induced lesions did not display
      immunoreactivity to either c-Jun or c-Fos antibodies. Results from this study
      suggest that the mechanisms by which DCA and TCA induce hepatocarcinogenesis in
      the male B6C3F1 mouse differ.

PMID- 9194408
TI  - Cadmium, gene regulation, and cellular signalling in mammalian cells.
AB  - Effects of the carcinogenic metal cadmium on the regulation of mammalian gene
      expression are reviewed and discussed in the light of observations on
      interference with cellular signal transduction pathways. Cadmium ions are taken
      up through calcium channels of the plasma membrane of various cell types, and
      cadmium is accumulated intracellularly due to its binding to cytoplasmic and
      nuclear material. At elevated cytotoxic concentrations, cadmium inhibits the
      biosyntheses of DNA, RNA, and protein, and it induces lipid peroxidation, DNA
      strand breaks, and chromosome aberrations. Cadmium compounds as such are only
      weak mutagens and clastogens. However, cadmium at noncytotoxic doses interferes
      with DNA repair processes and enhances the genotoxicity of directly acting
      mutagens. Hence, the inhibition of repair and detoxifying enzymes by this metal
      may partially explain the observed weak genotoxic properties of this metal.
      Nongenotoxic mechanisms upregulating intracellular signalling pathways leading to
      increased mitogenesis are discussed as major mechanisms for the interpretation of
      the carcinogenic activity by chronic cadmium exposure. About 1 microM cadmium
      stimulates DNA synthesis and cell proliferation in various cell lines, whereas
      more elevated concentrations are inhibitory. Cadmium enhances the expression of
      several classes of genes at concentrations of a few microM. It stimulates the
      expression of immediate early genes (c-fos, c-jun, and c-myc), of the tumor
      suppressor gene p53, and of genes coding for the syntheses of protective
      molecules, including metallothioneins, glutathione, and stress (heat shock)
      proteins. The mechanisms underlying the modulation of gene activity by cadmium
      are discussed in terms of interference with cellular signalling at the levels of
      cell surface receptors, cellular calcium and zinc homeostases, protein
      phosphorylation, and modification of transcription factors. In considering the
      available evidence, the carcinogenic properties of cadmium are interpreted using
      a multifactorial approach involving indirect genotoxicity (interference with DNA
      repair) and the upregulation of mitogenic signalling pathways.

PMID- 9194409
TI  - Toxicological effects of beryllium on platelets and vascular endothelium.
AB  - Although ample research has described the toxic effects of the metal beryllium on
      the respiratory apparatus, less is known about its effects on the vascular
      apparatus, including pulmonary blood vessels. We investigated the in vitro
      effects of beryllium on endothelial vascular adenosine diphosphatase activity and
      prostacyclin production in bovine aortic endothelium, and on nitric oxide release
      in isolated rabbit arteries. Rabbit and human platelet responsiveness was also
      evaluated. Beryllium inhibited vascular endothelial adenosine diphosphatase
      activity, prostacyclin production, and nitric oxide release, thus inducing
      functional alterations in vascular endothelial cells. It also induced platelet
      hyperreactivity to arachidonic acid, as shown by a lowering of the threshold of
      aggregating concentration and by concurrently increasing thromboxane production.
      In contrast, beryllium left the response to aggregating and nonaggregating
      concentrations of ADP and collagen unchanged. These findings show that beryllium
      may impair some vascular endothelial functions and alter the interaction between
      platelet and endothelial mediators.

PMID- 9194410
TI  - Pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) in the
      beagle dog and rhesus monkey: perspective on the reduced capacity of dogs to
      excrete this organic acid relative to the rat, monkey, and human.
AB  - The pharmacokinetics of triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid)
      were measured in the beagle dog and rhesus monkey and compared with the kinetics
      observed in rats and humans. In addition, studies were conducted in anesthetized
      dogs to better understand the mechanism by which [14C]triclopyr is eliminated in
      this species. Triclopyr was dissolved in distilled water, and administered as a
      single oral dose of 0.5, 5, or 20 mg/kg to three male dogs. A single male rhesus
      monkey was given an intravenous dose of 30 mg [14C]triclopyr/kg body wt on two
      occasions separated by 10 days. Anesthetized male dogs, were implanted with
      venous, arterial, and urethral catheters and given increasing amounts of
      triclopyr to produce plasma triclopyr levels ranging from 0.3 to 27 microg eq/mL.
      In the monkey, triclopyr was rapidly eliminated from the plasma (t1/2 = 6.3 hr)
      with >95% of the urinary 14C activity excreted within 24 hr postdosing. In the
      dog, orally administered triclopyr was rapidly and effectively absorbed at every
      dose level with virtually all of it excreted in the urine by 72 hr postdosing.
      However, the kinetics were slightly nonlinear, and the fraction of the dose
      excreted in the urine decreased with increasing dose. Several nonlinear processes
      may collectively contribute to the modest nonlinear pharmacokinetics in the dog.
      Plasma protein binding of triclopyr in the dog ranged from 94 to 99%, was
      nonlinear, and was an important determinant in the renal clearance of triclopyr.
      The nonlinear plasma protein binding indicates that glomerular filtration became
      disproportionately more important as plasma triclopyr concentration increased.
      There was good evidence for a high-affinity low-capacity active-secretory process
      that was saturated by low plasma triclopyr concentrations. As plasma triclopyr
      concentrations increased, tubular reabsorption begins to exceed secretion,
      resulting in decreased renal clearance. The volume of distribution, normalized
      for body weight, was constant across all species. While clearance and half-life
      could be allometrically scaled to body weight for the rat, monkey, and human, the
      dog had a much slower clearance and longer half-life for triclopyr elimination
      than predicted allometrically. These data demonstrate that the pharmacokinetics
      of triclopyr in the dog are markedly different than in rat, monkey, and human.

PMID- 9194411
TI  - Antioxidative and protective properties of extracts from leaves of the artichoke
      (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured
      rat hepatocytes.
AB  - Primary rat hepatocyte cultures exposed to tert-butylhydroperoxide (t-BHP) or
      cumene hydroperoxide were used to assess the antioxidative and protective
      potential of water-soluble extracts of artichoke leaves. Both hydroperoxides
      stimulated the production of malondialdehyde (MDA), particularly when the cells
      were pretreated with diethylmaleate (DEM) in order to diminish the level of
      cellular glutathione (GSH). Addition of artichoke extracts did not affect basal
      MDA production, but prevented the hydroperoxide-induced increase of MDA formation
      in a concentration-dependent manner when presented simultaneously or prior to the
      peroxides. The effective concentrations (down to 0.001 mg/ml) were well below the
      cytotoxic levels of the extracts which started above 1 mg/ml. The protective
      potential assessed by the LDH leakage assay and the MTT assay closely paralleled
      the reduction in MDA production and largely prevented hepatocyte necrosis induced
      by the hydroperoxides. The artichoke extracts did not affect the cellular level
      of glutathione (GSH), but diminished the loss of total GSH and the cellular
      leakage of GSSG resulting from exposure to t-BHP. Chlorogenic acid and cynarin
      accounted for only part of the antioxidative principle of the extracts which was
      resistant against tryptic digestion, boiling, acidification, and other
      treatments, but was slightly sensitive to alkalinization. These results
      demonstrate that artichoke extracts have a marked antioxidative and protective
      potential. Primary hepatocyte cultures seem suitable for identifying the
      constituents responsible for these effects and for elucidating their possible
      mode of action.

PMID- 9194412
TI  - Hepatic ploidy, nuclearity, and distribution of DNA synthesis: a comparison of
      nongenotoxic hepatocarcinogens with noncarcinogenic liver mitogens.
AB  - Most nongenotoxic hepatocarcinogens such as diethylhexyl phthalate (DEHP) and
      chlorendic acid (CEA) induce hepatocyte replicative DNA synthesis. However, not
      all mitogens are carcinogenic; in National Toxicology Program (NTP) studies 1,4
      dichlorobenzene (DCB) was not hepatocarcinogenic in the rat despite the induction
      of substantial hepatic DNA synthesis. We have examined the hypothesis that the
      profile of hepatocyte labeling index (LI) may dictate hepatocarcinogenic
      potential. Using flow cytometry, we investigated the effects of DEHP, CEA, and
      DCB on hepatocyte ploidy, nuclearity, and LI distribution among the
      ploidy/nuclearity classes in male Fischer 344 rats. Dosing was for 7 days at the
      dose and route employed previously in the NTP cancer bioassays. Unlike DEHP and
      CEA, DCB reduced the proportion of tetraploid cells (4N plus 2 x 2N) and
      increased the proportion of mononucleated octoploid (8N) cells. DCB and DEHP
      increased the mean hepatic LI (17 +/- 2 and 23 +/- 3%, respectively, compared
      with 1.4 +/- 0.4% in controls), whereas, as expected for a chronic inducer of S
      phase, CEA did not. LI was increased in all hepatocyte ploidy/nuclearity classes
      except the binucleated tetraploid cells (2 x 2N) and was elevated most in the
      mononucleated octoploid population (8N) (LI = 44 +/- 11, 49 +/- 14, and 1.3 +/-
      0.4% of 8N hepatocytes for DCB, DEHP, and control, respectively). In general, the
      effects of DCB on LI could not be distinguished from those of DEHP. However, DEHP
      tended to induce DNA synthesis in a greater proportion of 2N and 2 x 4N cells;
      future studies will analyze whether the induction of DNA synthesis in these small
      populations may be more relevant to hepatocarcinogenesis.

PMID- 9194413
TI  - Differential cytokine mRNA expression in mice after oral exposure to the
      trichothecene vomitoxin (deoxynivalenol): dose response and time course.
AB  - Acute oral exposure of B6C3F1 mice to vomitoxin (VT) has been previously shown to
      induce expression of mRNAs for cytokines that are characteristically produced in
      lymphoid tissues by macrophage and T cells. The purpose of this study was to
      evaluate the effects of VT dose on the expression of mRNAs for a cytokine profile
      consisting of TNF-alpha, IL-1beta, IL-6, IL-12, IFN-gamma, IL-2, IL-4, IL-5, IL
      10, IL-12, and TGF-beta and to measure the kinetics of these responses. The
      effects of a single oral exposure to 0, 0.1, 0.5, 1, 5, and 25 mg/kg BW of VT on
      cytokine mRNA abundance in spleen and Peyer's patches (indicators of systemic and
      mucosal immune compartments, respectively) were assessed at 2 hr postexposure
      using reverse transcriptase-polymerase chain reaction (RT-PCR) in combination
      with hybridization analysis. Both 5 and 25 mg/kg VT significantly induced the
      mRNAs for the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha; the T
      helper 1 cytokines IFN-gamma and IL-2; and the T helper 2 cytokines IL-4 and IL
      10, whereas lower doses had no effect. IL-12p40 mRNA was also induced but not IL
      12p35 mRNA. The effects were more pronounced in spleen than in the Peyer's
      patches. IL-5 and TGF-beta mRNAs were expressed constitutively in spleen and
      Peyer's patches but were not affected by VT. When cytokine mRNA levels were
      measured at 1, 2, 4, 8, and 24 hr after oral exposure to 25 mg/kg BW of VT, mRNA
      expression kinetics varied among cytokines or between spleen and Peyer's patches.
      The duration of elevated mRNA expression in spleen was 1-8 hr for TNF-alpha, IL
      6, IFN-gamma, and IL-10 and was 1-4 hr for IL-1beta, IL-12p40, IL-2, and IL-4. In
      Peyer's patches, duration periods were 1-8 hr for IL-6, IL-2, and IL-10; 1-4 hr
      for IL-1beta, IL-12p40, and TNF-alpha; and 1-2 hr for IFN-gamma. Serum levels of
      TNF-alpha, IL-6, and IFN-gamma were elevated 3 hr after exposure to 25 mg/kg VT,
      thus suggesting that elevation of splenic and Peyer's patch mRNA abundance
      correlated with increases in systemic production of these cytokines. Taken
      together, the results indicate that a single VT exposure rapidly induces gene
      expression in vivo for a wide range of cytokines with apparently complete
      recovery occurring after 24 hr. Elevated cytokine expression may play an
      important role in the pathophysiologic effects of VT and other trichothecenes.

PMID- 9194414
TI  - Effects of phenethyl isothiocyanate on acetaminophen metabolism and
      hepatotoxicity in mice.
AB  - Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous and other
      vegetables, is a potent inhibitor of cytochrome P450 2E1. This enzyme catalyzes
      the bioactivation of acetaminophen (APAP) and many other xenobiotics. The present
      study investigated the effects of PEITC on APAP metabolism and associated
      hepatotoxicity in Swiss-Webster mice. When PEITC (19-150 micromol/kg) was given
      to mice intragastrically 1 hr before or immediately prior to a toxic dose of
      APAP, the APAP-induced hepatotoxicity was significantly decreased or was
      completely prevented. The extent of toxicity was evaluated by mortality, serum
      levels of glutamic-pyruvic transaminase, lactate dehydrogenase, and liver
      histopathology. Pretreatment of mice with ethanol enhanced APAP hepatotoxicity;
      this enhanced toxicity could also be prevented by the administration of PEITC.
      PEITC treatment prevented the depletion of hepatic glutathione levels caused by
      oxidized APAP metabolites. PEITC treatment also significantly decreased the
      plasma levels of oxidized APAP metabolites (analyzed as APAP-glutathione, APAP
      cysteine, and APAP-N-acetylcysteine) and reduced the urinary excretion of APAP
      cysteine. In microsomal incubations, PEITC effectively inhibited the rate of APAP
      glutathione formation from APAP as well as the P450 2E1-dependent N
      nitrosodimethylamine demethylase and the P450 1A2-dependent ethoxyresorufin O
      deethylase activities. The protective action of PEITC against APAP toxicity is
      attributed to the blocking of APAP activation through inhibition of P450 enzymes.

PMID- 9194415
TI  - Physiologically based modeling of nonsteady state dermal absorption of
      halogenated methanes from an aqueous solution.
AB  - Dermal absorption of organic chemicals from aqueous solutions are a concern in
      both the workplace and the home. Organic chemicals are generally not very soluble
      in water and the exposure may never reach steady state because the concentration
      of chemical decreases during the exposure. In vivo animal studies which mimic
      human exposures, but are carefully controlled, are one way to measure absorption.
      Whole animal studies are superior to excised skin measurements, because the
      physiological responses including blood flow, metabolism, and biological defenses
      are present. In this study, we develop a physiologically based model for
      nonsteady state exposures to organic chemicals in aqueous solutions. A key
      feature of this model is a compartment which describes loss of chemical in the
      exposure solution due to absorption into the skin. We exposed rats to a range of
      aqueous concentrations of dibromomethane (2.4 to 9.4 mg/ml) and
      bromochloromethane (3.6 to 12.8 mg/ml) and measured blood concentrations during
      24-hr exposures. The blood concentrations peaked at about 1-2 hr and diminished
      to nearly nothing at 24 hr. Physiologically based models were used to estimate
      permeability coefficients for each of the exposures, although none of the
      exposures reached steady state due to the decreasing concentration of chemical on
      the surface of the skin. A constant permeability coefficient adequately described
      the blood concentrations during the prolonged exposure. Physiologically based
      models can be used to estimate permeability coefficients when the concentration
      of chemical on the skin is not constant. These permeability parameters can
      subsequently be used for assessing the risks in human exposure situations.

PMID- 9194416
TI  - Chronic, topical administration of 4-aminobiphenyl induces tissue-specific DNA
      adducts in mice.
AB  - While current human exposure to 4-aminobiphenyl (4-ABP) is mainly through
      inhalation, historically, occupational exposure occurred most often through the
      skin. 4-ABP targets the urinary bladder in humans, dogs, and rats and the liver
      and urinary bladder in mice. This study examines the time course of DNA adduct
      levels in mouse target tissues, liver and urinary bladder, and nontarget tissues,
      lung and skin, after repeated dermal exposure to subcarcinogenic doses of 4-ABP.
      It was found that, in female mice dermally treated with 50 nmol of 4-ABP twice
      weekly for 21 weeks, DNA adduct levels measured by 32P-postlabeling increased
      over time in target and nontarget tissues, but the greatest rate of accumulation
      occurred in urinary bladder. At 21 weeks liver, urinary bladder, and skin reached
      their highest median adduct levels of 55, 82, and 58, respectively. Median adduct
      levels in lung reached a maximum of 3.2 at 3 weeks of exposure. An adduct which
      had similar chromatographic properties to a standard previously identified as N
      (deoxyguanosin-8-yl)-4-aminobiphenyl was the primary adduct detected in all
      tissues. There were significant correlations in adduct levels between liver and
      urinary bladder and liver and skin, but not between skin and urinary bladder.
      These data suggest that urinary bladder adducts are the result of hepatic and not
      dermal activation. However, adducts were detected at relatively high levels in
      skin but not in lung, suggesting that skin may have the metabolic capacity to
      activate 4-ABP when it is applied topically.

PMID- 9194417
TI  - The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of
      permethrin and carbaryl.
AB  - Simultaneous exposure to DEET and permethrin was recently proposed to be
      associated with the "Gulf War Syndrome." However, no studies have reported the
      percutaneous absorption of DEET and permethrin when applied simultaneously to the
      skin as a mixture, the relevant route of exposure in the Persian Gulf. The
      present study quantitates percutaneous absorption of DEET and permethrin after
      coadministration to rodent and pig skin in vitro. Dosing solutions were also
      prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare
      vehicle effects on percutaneous absorption of permethrin and DEET. The influence
      of DEET on carbaryl absorption and dermal disposition was also assessed in pig
      studies to statistically demonstrate DEET effects in acetone or DMSO and
      different solvent concentrations. Topical application of permethrin + DEET
      resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2
      1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a
      finding suggesting that DEET decreased permethrin absorption. DEET also inhibited
      carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures.
      Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For
      DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin
      (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was
      greater with DMSO and acetone than with ethanol in rat and mouse skin. These
      studies support DEET, but not permethrin or carbaryl, as having sufficient
      systemic exposure to potentially cause signs of toxicity when simultaneously
      applied with pesticides. Furthermore, these studies demonstrated that DEET does
      not necessarily enhance dermal absorption of all toxicants as was originally
      hypothesized.

PMID- 9194418
TI  - Using structural information to create physiologically based pharmacokinetic
      models for all polychlorinated biphenyls.
AB  - Physiologically based pharmacokinetic (PBPK) models are useful in describing the
      distribution, metabolism, and fate of xenobiotics across multiple species. The
      eventual goal of the present research is to create PBPK models for all 209
      polychlorinated biphenyls (PCBs). Key parameters in any PBPK model are the tissue
      to-blood partition coefficients. Tissue:blood partition coefficients relate the
      compound's concentration in a target tissue to its concentration in blood under
      equilibrium conditions. Data on the adipose:plasma partition coefficients of 24
      PCBs were used in a regression analysis to find an expression for the
      adipose:plasma partition coefficient as a function of molecular structure. Using
      stepwise regression, it was found that three simple structural descriptors were
      sufficient to predict adipose:plasma partition coefficients for all 209 PCB
      congeners. Data on the distribution of PCBs among blood components were used to
      derive the adipose:blood partition coefficient from the adipose:plasma partition
      coefficient. The lipid contents of liver, muscle, and skin were used to derive
      the tissue:blood partition coefficient for those tissues from the adipose:blood
      partition coefficient. These results allow for the calculation of tissue:blood
      partition coefficients for liver, skin, muscles, and fat for all 209 PCB
      congeners.

PMID- 9194419
TI  - Influence of acid aerosol droplet size on structural changes in the rat lung
      caused by acute exposure to sulfuric acid and ozone.
AB  - To investigate whether aerosol droplet size influences structural changes in the
      lung produced by short-term, concomitant exposure to ozone and sulfuric acid,
      groups of 10 rats were exposed 4 hr/day for 2 days to filtered air, 0.6 ppm
      ozone, 0.5 mg/m3 fine (aerosol mass median diameter (MMD) = 0.3 microm) or
      ultrafine (MMD = 0.06 microm) sulfuric acid, or a mixture of ozone and 0.5 mg/m3
      fine or ultrafine sulfuric acid. The volume percentage of total parenchyma
      containing markedly to severely injured alveolar septae was measured
      morphometrically. There were no differences between the ultrafine or fine acid
      exposure groups and the sham group for any of the morphologic endpoints. Volume
      percentage of markedly to severely injured tissue was increased in the ultrafine,
      but not fine, mixture animals when compared with the ozone-only group. In
      addition, a synergistic interaction between ozone and ultrafine, but not fine,
      sulfuric acid was found for this endpoint. The bromodeoxyuridine cell labeling
      index in the periacinar region was greater in the rats exposed to the fine
      sulfuric acid and ozone mixture than that in rats exposed to ozone alone, and a
      synergistic interaction between ozone and fine sulfuric acid was found for this
      end point. None of the exposures produced any changes in ventilatory parameters.
      Thus, acid aerosol droplet size was found to influence the effect of sulfuric
      acid in modifying ozone-induced structural changes in the rat lung.

PMID- 9194420
TI  - Adjuvant effect of respiratory irritation on pulmonary allergic sensitization:
      time and site dependency.
AB  - It has been suggested that airway irritation, by acting as an adjuvant, as well
      as producing damage, may be an important factor related to asthma. The present
      study examined the window of time following acute upper and lower airway irritant
      exposure to determine the period of increased risk of immunological
      sensitization. Brown Norway rats were exposed to 87 ppm NO2 or 1000 ppm NH3 for 1
      hr. A 30-min ovalbumin (OVA) exposure of 18.14 microg/liter air was given at
      various times based upon the time course of irritant associated inflammatory
      response (either immediately prior to or 1 or 7 days after the irritant
      exposure). OVA-only, NO2-only or NH3-only controls, and saline controls were also
      studied. Weekly booster exposures of OVA (or saline) were given. Circulating OVA
      specific IgE, IgA, and IgG levels were quantified periodically during the 6 weeks
      of the study. Bronchoalveolar lavage (BAL) was also performed to examine the
      inflammatory response to allergic and irritant challenge. Significant increases
      in OVA-specific IgE, IgG, and IgA antibody titers were seen in rats given the
      sensitizing OVA exposure within 1 day of the NO2, but not NH3 exposures.
      Enhancement of cellular infiltrate in BAL was noted in groups given the
      sensitizing OVA exposure within 1 day of the NO2 or NH3. It is concluded that the
      inflammatory and immunological response to antigen exposure can be modified by
      the site of respiratory tract irritation and the relative times of irritant and
      antigen exposure.

PMID- 9194421
TI  - Hydroxylated polychlorinated biphenyl metabolites are anti-estrogenic in a stably
      transfected human breast adenocarcinoma (MCF7) cell line.
AB  - Hydroxylated metabolites of polychlorinated biphenyls (OHCBs) have been
      identified in blood of marine mammals, fish-eating birds, and humans at
      concentrations in some cases exceeding those of the unmetabolized polychlorinated
      biphenyls (PCBs). OHCBs have been associated with inhibition of vitamin A and
      thyroxin transport, estrogenicity in a mouse uterotrophic assay, and feminization
      of male turtle sexual development. OHCBs, representing both environmentally
      derived and laboratory exposure-derived metabolites, were tested in an in vitro
      bioassay utilizing an estrogen-responsive human breast adenocarcinoma cell line
      (MCF7-LUC) stably transfected with a luciferase reporter gene linked to estrogen
      responsive elements. OHCB activity was tested at three different media
      concentrations of 17beta-estradiol (E2), comparing the concentration-response
      curves using charcoal-stripped medium (0.0009 nM E2), and two physiologically
      relevant E2 concentrations (0.1 and 1.0 nM E2). Eleven of 13 OHCBs tested were
      anti-estrogenic. Evidence for an estrogen receptor mediated mechanism of action
      was apparent for only two OHCBs-4-OH-2',3,3',4',5,5'-Cl6-biphenyl and 4,4'-(OH)2
      3,3',5,5'-Cl4-biphenyl. These two have not been identified in environmental
      samples. The remaining OHCBs exhibited "anti-estrogenicity" that was related to
      their effect on cell viability and, therefore, cannot be described as exhibiting
      "hormone disruption" solely by an estrogen receptor mediated mechanism. OHCB anti
      estrogenic activity was eliminated in the presence of E2 concentrations normally
      found in humans, except for 4,4'(OH)2-3,3',5,5'-Cl4-biphenyl. 4-OH-2',3',4',5'
      Cl4-biphenyl and 4-OH-2',4',6'-Cl3-biphenyl were partial estrogen agonists,
      exhibiting weak estrogenicity in the presence of 0.0009 nM E2 and weak anti
      estrogenicity in the presence of 0.1 and 1 nM E2. Human metabolites of PCBs were
      not estrogenic in MCF7 cells.

PMID- 9194422
TI  - Potent protective effect of melatonin on chromium(VI)-induced DNA single-strand
      breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat
      hepatocytes.
AB  - Incubation of primary cultures of rat hepatocytes with K2Cr2O7 plus the pineal
      hormone melatonin resulted in a marked decrease in cellular levels of DNA single
      strand breaks caused by K2Cr2O7. Cellular treatment with melatonin also
      suppressed both dichromate-induced cytotoxicity, as evaluated by the leakage of
      lactate dehydrogenase, and lipid peroxidation, as monitored by malondialdehyde
      formation. In addition, treatment with melatonin attenuated the suppression of
      the levels of vitamins E and C as well as the inhibition of catalase activity
      attributed to K2Cr2O7. However, melatonin had no influence on cellular level of
      glutathione and the activity of glutathione reductase, glutathione peroxidase,
      superoxide dismutase, and alkaline phosphatase suppressed by dichromate. Under
      the same experimental conditions, cellular uptake and distribution of Cr were not
      affected by melatonin. Electron spin resonance (ESR) studies showed that
      melatonin did not affect the formation of Cr(V) complexes in the reaction of
      K2Cr2O7 with reduced glutathione; however, melatonin caused a 25% decrease in the
      levels of Cr(V)-related hydroxyl radicals in vitro. These results indicate that
      melatonin protects cells from Cr(VI)-induced DNA strand breaks, cytotoxicity, and
      lipid peroxidation, possibly through its ability to increase cellular levels of
      vitamins E and C as well as catalase activity and/or to directly scavenge toxic
      hydroxyl radicals in cells.

PMID- 9194423
TI  - Effect of coexposure to methyl ethyl ketone (MEK) on n-hexane toxicokinetics in
      human volunteers.
AB  - In order to study the effects of methyl ethyl ketone (MEK) on the toxicokinetics
      of n-hexane and, in particular, the formation of 2,5-hexanedione from n-hexane in
      humans, volunteers were exposed to n-hexane (approx. 60 ppm, 2.4 microM in the
      inhaled air) with or without simultaneous inhalatory coexposure to MEK for 15.5
      min. The concentration-time course of n-hexane (in exhaled alveolar air) and its
      neurotoxic metabolite, 2,5-hexanedione (in serum), were studied. The
      concentration-time courses obtained after exposure to n-hexane alone were
      compared with those obtained after coexposure to 200 or 300 ppm MEK in the same
      volunteer on the same day. No effect of MEK was observed on the concentration
      time course of exhaled n-hexane. The concentration-time course of the metabolite,
      2,5-hexanedione, revealed a decrease in the rate of formation of 2,5-hexanedione
      (about three-fold) after coexposure to MEK. Furthermore, the time to reach the
      peak concentration was increased from 18 to 30 min after the start of exposure.
      These changes in the concentration-time course of 2,5-hexanedione caused by MEK
      are most likely the result of inhibition of the biotransformation of one of the
      intermediate steps in the conversion of n-hexane to 2,5-hexanedione. These
      results indicate that the interaction of n-hexane and MEK leads to a decreased
      concentration of the neurotoxic metabolite 2,5-hexanedione (after short-term,
      acute exposure).

PMID- 9194424
TI  - Variation in induction of human placental CYP2E1: possible role in susceptibility
      to fetal alcohol syndrome?
AB  - Fetal alcohol syndrome occurs in less than 10% of women who drink heavily during
      pregnancy. One potential mechanism for this intersubject variation is differences
      in placental alcohol metabolism. Alcohol dehydrogenase is present at low
      concentrations in the placenta and is not inducible. CYP2E1 has not been found in
      human placentas at early gestation time points or in random term placentas.
      Hepatic CYP2E1 is induced by alcohol and other environmental agents, but
      induction varies among heavy drinkers and may be genetically controlled. To test
      whether CYP2E1 is induced in placenta by heavy drinking during pregnancy, we
      performed a Western blot analysis on placental microsomes from women (n = 8)
      whose periconceptional average daily absolute alcohol intake was greater than 1
      ounce. Using anti-human CYP2E1, bands consistent with CYP2E1 were identified in
      six samples, although considerable variation among individuals was observed.
      Among drinking mothers, offspring head size was smaller among those with
      placental CYP2E1 (p = 0.04). The association between the presence of the protein
      and smaller birth weight and birth length was equivocal (p = 0.09). Our data are
      consistent with placental CYP2E1 being inducible by drinking, but with induction
      being variable among heavy drinking women. We speculate intersubject variation in
      induction may have a genetic basis and may play a role in susceptibility to
      alcohol related defects.

PMID- 9194425
TI  - Potential of CT angiography in acute ischemic stroke.
AB  - PURPOSE: To study the ability of CT angiography to show intracranial arterial
      occlusion and collateral blood flow in patients with acute stroke. METHODS:
      Twenty-one patients with acute nonhemorrhagic stroke were studied prospectively
      with conventional CT, CT angiography, and digital subtraction angiography. On the
      basis of CT angiographic findings, two neuroradiologists independently assessed
      the site of arterial occlusion, the contrast enhancement in arterial branches
      beyond the occlusion as a measure of collateral blood supply, and the extent of
      diminished parenchymal enhancement; they then predicted the extent of ischemic
      infarction. RESULTS: Both raters correctly assessed all trunk occlusions of the
      basilar artery (n = 4), the internal carotid artery (n = 4), and the middle
      cerebral artery (n = 9). The chance adjusted interrater agreement was kappa =
      .78. The assessment of branch occlusions of the middle cerebral artery was less
      reliable. The agreement rate in judging the collateral state in 17 occlusions in
      the anterior cerebral circulation was 88%. The size of 21 (62%) of 34 hemispheric
      infarctions was predicted correctly. CONCLUSION: CT angiography quickly and
      reliably adds important information to conventional CT studies in cases of acute
      ischemic stroke. It shows the site of occlusion, the length of the occluded
      arterial segment, and the contrast-enhanced arteries beyond the occlusion as an
      estimate of collateral blood flow.

PMID- 9194426
TI  - CT angiography in the evaluation of acute stroke.
AB  - PURPOSE: To determine the worth of CT angiography of the circle of Willis as a
      supplement to routine CT in the examination of patients with symptoms of acute
      stroke in terms of its depiction of the number and distribution of arterial
      stenoses or occlusions. We also sought to compare the accuracy of CT angiography
      with MR angiography and/or digital subtraction angiography (DSA). METHODS: One
      hundred forty-five patients with symptoms of acute stroke were examined with
      routine head CT and CT angiography of the circle of Willis. MR angiography was
      also performed in 27 patients and DSA in 28 patients. CT and MR angiograms and
      DSAs were reviewed for stenoses or occlusions involving the vessels about the
      circle of Willis. MR and CT angiograms were also evaluated for image quality, and
      the corresponding routine CT and MR studies were evaluated for the presence of
      arterial infarction. RESULTS: CT angiograms were rated good or excellent in 89%
      of cases whereas MR angiograms were rated good or excellent in 92% of cases.
      Arterial stenoses or occlusions were present on 43% of CT angiograms, 48% of MR
      angiograms, and 21% of DSAs. Findings were in agreement in 98% of the vessels
      analyzed by CT angiography and MR angiography. Similarly, there was overall
      agreement of findings in 99% of vessels analyzed by CT angiography and DSA. None
      of the patients had any immediate adverse reactions after administration of
      intravenous nonionic iodinated contrast material. CONCLUSION: CT angiography is
      an accurate and safe method for evaluating arterial stenoses or occlusions in the
      vessels about the circle of Willis. CT angiography should be used in patients
      with symptoms of acute stroke for whom evaluation of the intracranial vasculature
      is desirable.

PMID- 9194427
TI  - CT angiography in acute ischemic stroke: the right tool for the job?

PMID- 9194428
TI  - MR angiography of ruptured aneurysms in acute subarachnoid hemorrhage.
AB  - PURPOSE: To determine the efficacy of high-resolution MR angiography for the
      prospective diagnosis of ruptured aneurysms in acute subarachnoid hemorrhage.
      METHODS: We used 3-D time-of-flight MR angiography with a large image matrix (193
      x 512 frequency-encoding steps), magnetization transfer saturation, and a
      variable flip-angle excitation (tilted optimized nonsaturating excitation [TONE])
      to study 28 patients with acute subarachnoid hemorrhage. The MR angiograms were
      compared with intraarterial digital subtraction angiographic (IA-DSA) images.
      RESULTS: Thirty-five (90%) of 39 aneurysms were detected prospectively with MR
      angiography. At least one aneurysm was identified with MR angiography in 25 (96%)
      of 26 patients with aneurysms proved by IA-DSA. Although four aneurysms were
      missed prospectively, three of these were detected retrospectively with MR
      angiography. Six aneurysms (18%) of those evident on MR angiograms were 3 mm or
      less in diameter. In one patient, additional targeted maximum intensity
      projections were greatly helpful for the ensuing IA-DSA by determining the
      optimial projection angle by which to depict a ruptured aneurysm that neither
      routine MR angiography nor routine IA-DSA detected. CONCLUSION: High-resolution
      MR angiography may be a useful diagnostic technique for detecting ruptured
      aneurysms, even in patients with acute subarachnoid hemorrhage. Initial MR
      angiography offers valuable and reliable information on ruptured aneurysms in
      acute subarachnoid hemorrhage, allowing the optimization of projection angles at
      conventional angiography.

PMID- 9194429
TI  - The circle of Willis.

PMID- 9194430
TI  - The low sensitivity of fluid-attenuated inversion-recovery MR in the detection of
      multiple sclerosis of the spinal cord.
AB  - PURPOSE: To confirm the expected superiority of fluid-attenuated inversion
      recovery (FLAIR) over conventional fast spin-echo MR imaging in the detection of
      multiple sclerosis (MS) of the spinal cord. METHODS: Fifteen subjects with known
      MS involving the spinal cord and brain were studied prospectively. The entire
      cord was imaged with a phased-array coil on a 1.5-T MR system. Sagittal T1
      weighted and fast spin-echo proton density- and T2-weighted images were followed
      by fast FLAIR images. FLAIR parameters were varied to optimize lesion conspicuity
      with optimal inversion times (TIs) ranging from 2400 to 2600. Lesion conspicuity
      and detection were compared between the fast spin-echo and FLAIR images by three
      radiologists who reached agreement by consensus. RESULTS: The FLAIR technique
      effectively suppressed cerebrospinal fluid (CSF) signal and reduced CSF pulsation
      and truncation artifacts in all cases. Shorter imaging parameters (repetition
      time of 4000 to 6000, TI of 1500 to 2000) uniformly decreased lesion conspicuity
      in all subjects. Of 11 cord lesions in five subjects imaged with the longer
      parameters (repetition time of 8000 to 11,000, TI of 2400 to 2600), three were
      not seen on FLAIR images, four were less conspicuous on FLAIR images, and four
      were seen equally or better on FLAIR images. CONCLUSION: Although successful in
      suppressing CSF signal and reducing imaging artifacts, fast FLAIR imaging appears
      unreliable in the detection of MS lesions in the spinal cord.

PMID- 9194431
TI  - MR of the spinal cord in multiple sclerosis: relation to clinical subtype and
      disability.
AB  - PURPOSE: To determine whether the MR appearance of the spinal cord in patients
      with multiple sclerosis (MS) differs according to clinical subtype. METHODS: The
      spinal cords of 20 healthy control subjects and 60 patients with MS (22 with
      relapsing-remitting disease, 22 with secondary-progressive disease, and 16 with
      primary-progressive disease) were examined with sagittal dual-echo spin-echo MR
      imaging and with axial T2*-weighted gradient-echo MR imaging. Two interpreters
      scored the images for focal lesions and for diffuse abnormalities. Cross
      sectional areas of the cords were measured at the C-2 level. RESULTS: No
      abnormalities were found in any of the control subjects nor in two of the
      patients. Fifty (83%) of 60 patients had focal lesions. Diffuse abnormality and
      focal lesions were found in 50% of patients with secondary-progressive MS, in 25%
      of patients with primary-progressive disease, and in 18% of patients with
      relapsing-remitting disease. Diffuse abnormality without focal lesions was found
      in seven patients with primary-progressive MS and in one patient with secondary
      progressive MS. Patients with diffuse abnormalities had a smaller cross-sectional
      area of the spinal cord and they suffered from more disability than did patients
      without diffuse abnormalities. CONCLUSION: The MR appearance of the spinal cord
      differs among clinical subgroups of MS. Diffuse abnormality of the spinal cord is
      associated with a progressive clinical course and greater disability.

PMID- 9194432
TI  - High-resolution diffusion-weighted MR of fresh and fixed cat spinal cords:
      evaluation of diffusion coefficients and anisotropy.
AB  - PURPOSE: To use high-resolution diffusion-weighted and calculated apparent
      diffusion coefficient (ADC) MR imaging to determine whether fixation and storage
      influence diffusion anisotropy in white matter tracts of cat spinal cord
      specimens. METHODS: Four cat cord specimens were imaged using a diffusion
      weighted spin-echo sequence. Diffusion encoding was applied in the section-select
      axis (parallel to white matter tracts) and in the read axis (perpendicular to
      white matter tracts). Five sets of axial diffusion-weighted images were acquired
      with b values ranging from 0 to 800 s/mm2 and used to obtain calculated ADC
      images and to determine diffusion coefficients in different regions of the white
      matter tracts. RESULTS: After cord fixation, a decrease in T2 relaxation and spin
      density in the white matter caused the signal intensity to appear similar on
      diffusion-weighted images when the diffusion-probing gradient was applied along
      both the section-select and read axes. On the calculated ADC images, however,
      distinct differences in signal intensities were seen in the section-select and
      read axes. CONCLUSION: Although there is little difference in signal intensity in
      the white matter tracts on diffusion-weighted images when diffusion encoding is
      applied in the section-select or read axis in the fixed specimens, calculated ADC
      images confirm that diffusion anisotropy is maintained. Therefore, calculated ADC
      images may be helpful in the evaluation of fixed spinal cord specimens.

PMID- 9194433
TI  - Proton MR spectroscopy of squamous cell carcinoma of the extracranial head and
      neck: in vitro and in vivo studies.
AB  - PURPOSE: To determine the ability of in vitro one-dimensional and two-dimensional
      proton MR spectroscopy to help differentiate squamous cell carcinoma of the
      extracranial head and neck from normal tissues and to correlate the in vitro
      observations with clinical studies. METHODS: In vitro 1-D and 2-D correlated
      proton MR spectroscopy (11 T) was performed in tissue specimens of squamous cell
      carcinoma of the head and neck (n = 19), in normal tissue (n = 13), in metastatic
      cervical lymph nodes (n = 3), and in a squamous cell carcinoma cell line. In vivo
      1-D proton MR spectroscopy (1.5 T) was performed in patients with squamous cell
      carcinoma (n = 7) and in healthy volunteers (n = 7). The ratio of the areas under
      the choline (Cho) and creatine (Cr) resonances were calculated for 1-D proton MR
      spectra for the in vitro tissue studies and correlated with the in vivo studies.
      Data from in vitro 2-D correlated spectroscopy were analyzed for differences in
      the presence or absence of various metabolites in samples of tumor and normal
      tissue. Statistical analysis consisted of 2 x 2 factorial repeated measures
      analysis of variance (ANOVA), discriminate analysis, and chi2 test. RESULTS: The
      mean in vitro 1-D proton MR spectroscopic Cho/Cr ratio was significantly higher
      in tumor than in normal tissue. The difference between the mean ratios appeared
      to increase with increasing echo time. All in vivo tumor Cho/Cr ratios were
      greater than the calculated mean in vitro tumor ratio, whereas six of the seven
      volunteers had no detectable Cho and Cr resonances. Two-dimensional correlated MR
      spectroscopic data revealed that a variety of amino acids have a significantly
      greater likelihood of being detected in tumor than in normal tissues.
      CONCLUSIONS: One-dimensional and 2-D proton MR spectroscopy can help
      differentiate primary squamous cell carcinoma and nodal metastases containing
      squamous cell carcinoma from normal tissue both in vitro and in vivo. In
      addition, 2-D spectroscopy can help identify the presence of certain amino acids
      in squamous cell carcinoma that are not detected in normal tissue.

PMID- 9194434
TI  - 111In octreotide scintigraphy in the evaluation of head and neck lesions.
AB  - PURPOSE: To evaluate indium 111 octreotide scintigraphy for the detection of
      suspected neuroendocrine lesions of the head and neck. METHODS: After receiving 6
      mCi of 111In octreotide, 22 patients with suspected lesions of the head and neck
      were examined with both planar and single-photon emission CT (SPECT). Static
      images, obtained at 4 hours, included the head/neck, chest, abdomen, and pelvis.
      Additional SPECT images were obtained at 4 or 24 hours. Studies were compared
      with available conventional radiologic examinations (12 CT, 11 MR, and three
      angiographic studies) as well as with clinical and pathologic findings. RESULTS:
      Eighteen of the 22 patients had abnormal findings at scintigraphy. Eleven
      paragangliomas were seen in 10 patients, metastatic medullary thyroid carcinoma
      in three patients, thyroid adenoma in two patients, and Merkel cell tumor,
      carcinoid, and plasmacytoma in one patient each. Surgical confirmation was
      available in 13 patients. The smallest lesion detected was 1.5 cm. There was one
      false-positive and one false-negative examination. CONCLUSION: 111In octreotide
      scintigraphy is a useful imaging tool for the detection of primary and metastatic
      neuroendocrine tumors of the head and neck that are larger than 1.5 cm. This
      technique enables distinction of glomus tumors from other masses (such as
      neuromas) and can be used in the postoperative setting to distinguish scar from
      recurrent paraganglioma. Since it is an examination of the entire body, it has
      great utility for detecting multicentric paraganglioma and for screening patients
      with familial paraganglioma.

PMID- 9194435
TI  - Effect of intraarterial papaverine on cerebral circulation time.
AB  - PURPOSE: To measure the mean cerebral circulation time (CCT) in patients with
      symptomatic vasospasm stemming from subarachnoid hemorrhage and to determine any
      change after papaverine treatment. METHODS: We studied 27 patients who received
      intraarterial papaverine from November 1992 to August 1995 to determine the CCT
      in 59 carotid territories. CCT was measured from the first image in which
      contrast was seen above the supraclinoid internal carotid artery to the peak
      filling of parietal cortical veins. Angiograms at the time of presentation were
      examined in 19 of the 27 patients. A control population of 19 patients (30
      carotid territories) was also studied. RESULTS: The mean CCT on presentation was
      6.8 seconds +/- 1.1. The prepapaverine mean CCT was 6.1 seconds +/- 1.2. The
      immediate postpapaverine mean CCT was 3.8 seconds +/- 0.8. CCT decreased in 58 of
      59 territories treated with papaverine; the mean change was -35.7%. In eight of
      these patients, CCT rose on the following day to 6.1 seconds +/- 1.1. In the
      control group, mean CCT was 5.9 seconds +/- 0.8. The mean CCT in patients with
      subarachnoid hemorrhage was slightly prolonged on presentation relative to that
      in control subjects. CONCLUSION: Intraarterial papaverine produces a consistent
      decrease in CCT in patients with vasospasm.

PMID- 9194436
TI  - Hydrophilic coatings diminish adhesion of glue to catheter: an in vitro
      simulation of NBCA embolization.
AB  - PURPOSE: To determine whether new hydrophilic microcatheter coatings exhibit
      characteristics that diminish the chance of permanent endovascular glue adhesion
      during liquid acrylic embolization. METHODS: Common hydrophilic and
      nonhydrophilic microcatheters (both flow-directed and over-the-wire) used in
      neurointerventional procedures were evaluated in vitro for liquid acrylic
      (Histoacryl and Avacryl)-to-catheter bond strength, catheter endovascular
      friction, and catheter stretch (tensile strength). Sufficient test repetitions
      were acquired to achieve statistical significance. RESULTS: The bond strength
      between hydrophilically coated catheters and NBCA was significantly weaker than
      between nonhydrophilic catheters and NBCA. Hydrophilic catheter coating reduced
      dynamic endovascular friction by 30% to 35%. All flow-directed catheters
      exhibited considerably more stretch (less tensile strength) and therefore were
      more prone to fracture during withdrawal than over-the-wire systems. Histoacryl
      bonded to both hydrophilic and nonhydrophilic catheters with a significantly
      greater force than did Avacryl. CONCLUSION: Hydrophilically coated catheters
      should be less likely to exhibit permanent endovascular fixation during acrylic
      embolization because of a weaker catheter-NBCA bond and because of reduced
      catheter friction (allowing a larger portion of any applied catheter withdrawal
      force to be transmitted to the catheter tip with less force dissipated along the
      catheter resulting in stretch). A significant difference in NBCA types
      (Histoacryl and Avacryl) was discovered: Avacryl developed a significantly weaker
      bond with all catheter types.

PMID- 9194437
TI  - Chronic thalamic stimulation with three-dimensional MR stereotactic guidance.
AB  - PURPOSE: To report a method of electrode implantation in the ventralis
      intermedius nucleus of the thalamus for the treatment of tremor using a 3-D
      stereotactic MR imaging technique. METHODS: Five patients (three men and two
      women; mean age, 59 years) with medically refractory tremor had intrathalamic
      implantation of a stimulating electrode. Stereotactic MR imaging was performed on
      a 1.5-T unit equipped with an MR-compatible Leksell G stereotactic frame fixed to
      the patient's head. Calculation of the coordinates of the theoretical target was
      based on the coordinates of the anterior commissure, the posterior commissure,
      and the midline sagittal plane as determined via stereotactic MR imaging. During
      the surgical procedure, the best position for the stimulating electrode was
      determined by electrophysiological and clinical studies. Postoperative MR control
      studies were done in all cases to verify the position of the electrode. RESULTS:
      Stereotactic MR imaging allowed precise implantation of the stimulating electrode
      in all patients. Electrode stimulation produced a 90% reduction of the tremor in
      two patients, an 80% and 70% reduction in one patient each, and a persistent
      microthalamotomy-like effect in the fifth patient. Examination of the MR control
      studies showed that mean error in the positioning of the electrodes was 0.77 +/-
      0.6 mm (mean +/- SD) in the x direction and 0.80 +/- 1.02 mm in the y direction.
      CONCLUSION: Although our series is relatively small, the precision achieved with
      stereotactic MR imaging proves that it can be used with confidence for precise
      functional neurosurgical procedures.

PMID- 9194438
TI  - The anterior epitympanic recess: CT anatomy and pathology.
AB  - PURPOSE: To describe the variation in size and shape of the anterior epitympanic
      recess and to discuss pathologic processes that affect this space. METHODS: Axial
      CT scans of the temporal bones of 31 adults and 19 children were reviewed
      retrospectively to ascertain the morphology and size of the anterior epitympanic
      recess. Selected confirmed disease processes involving this space were studied.
      RESULTS: The anterior epitympanic recess, which is consistently identified on
      axial CT scans, is either single or multicelled. In our study, it was made up of
      a solitary cell in 61 of 100 ears. Side-to-side symmetry in shape was present in
      78 of 100 cases. The size of a solitary air cell ranged from 1.0 to 7.0 mm.
      CONCLUSIONS: The configuration of the anterior epitympanic recess is readily
      affected by a persistent stapedial artery, by facial nerve schwannomas, by
      hemangiomas of the facial nerve canal in the geniculate region, and by congenital
      and acquired cholesteatomas. Familiarity with the CT anatomy of this space
      facilitates recognition of these pathologic processes at an early stage.

PMID- 9194439
TI  - Contrast-enhanced MR of the facial nerve in patients with posttraumatic
      peripheral facial nerve palsy.
AB  - PURPOSE: To estimate the value of noncontrast and contrast-enhanced T1-weighted
      MR imaging in detecting the underlying mechanisms of injury and regeneration in
      immediate- or delayed-onset posttraumatic peripheral facial nerve palsy. METHODS:
      Twenty-four patients with posttraumatic peripheral facial nerve palsy were
      examined on a 1.5-T MR imaging unit with precontrast and postcontrast T1-weighted
      spin-echo and gradient-echo sequences. RESULTS: Abnormal enhancement of the
      distal intrameatal nerve segment was visible in 92% of the patients up to 2 years
      after their initial trauma. A hematoma within the geniculate ganglion was seen in
      33% of the patients with a longitudinal fracture. The greater superficial
      petrosal nerve (in 32% of patients) and the geniculate ganglion (in 48% of
      patients) were thick and intensely enhancing. Hematoma within the
      cochlea/vestibule or enhancement of the cochlea/vestibule and the
      vestibulocochlear (eighth) nerve was observed in transverse fractures.
      CONCLUSION: MR images can show long-lasting abnormal nerve enhancement,
      especially in the distal intrameatal nerve segment, related to the long-lasting
      breakdown of the blood/peripheral nerve barrier associated with nerve
      degeneration and regeneration after traumatic stretching of the greater
      superficial petrosal nerve. Additionally, intraoperatively observed perineural
      and intraneural scar formation leads to thickening and intense enhancement of the
      affected nerve segments on MR images. A hematoma in the region of the geniculate
      ganglion can be seen in some but not all patients. Associated damage of the inner
      ear structures in patients with transverse fractures is also visible on MR
      images.

PMID- 9194441
TI  - Value of single-voxel proton MR spectroscopy in temporal lobe epilepsy.
AB  - PURPOSE: To study the value of different parameters derived from single-voxel
      proton MR spectroscopy of the mesial temporal lobes in the lateralization of the
      epileptogenic zone in patients with temporal lobe epilepsy. METHODS: We studied
      12 healthy volunteers and 21 patients with temporal lobe epilepsy refractory to
      medical treatment, which was clearly lateralized with electroencephalography
      (EEG) and MR imaging. The mesial temporal lobes were investigated with single
      voxel proton MR spectroscopy using a point-resolved spectroscopic sequence with
      an echo time of 135 milliseconds. The normalized concentration of N
      acetylaspartate (NAA), creatine (Cr), and choline-containing compounds (Cho), and
      the metabolite ratios NAA/Cho+Cr, NAA/Cr, Cho/Cr, and NAA/Cho were calculated
      from the spectra. Using these values and an asymmetry index, we assigned the
      patients to one of five lateralization categories. RESULTS: The most consistent
      MR spectroscopic parameter for clear lateralization was the NAA/Cho+Cr ratio,
      followed by the NAA ratio. But with an adequate asymmetry index, the epilepsy in
      17 (81%) of 21 patients could be lateralized by EEG and MR imaging with both
      parameters concordantly. Symmetric bilateral abnormalities were found in four of
      the 21 patients with NAA/Cho+Cr and in only one of the 21 patients with NAA. With
      both parameters, no contradictory lateralization was found; however, this was
      indeed the case with the remaining ratios, NAA/Cr, Cho/Cr, and NAA/Cho, in two,
      three, and one of the patients, respectively. A statistically significant
      decrease in NAA was found on the epileptic side, but also on the contralateral
      side. CONCLUSION: With an adequate asymmetry index, NAA/Cho+Cr and NAA are
      equally sensitive in predicting the side of involvement in patients with
      unilateral temporal lobe epilepsy.

PMID- 9194440
TI  - Representation of the visual field in the striate cortex: comparison of MR
      findings with visual field deficits in organic mercury poisoning (Minamata
      disease).
AB  - PURPOSE: To compare MR imaging findings of the striate cortex with visual field
      deficits in patients with Minamata disease and to reestimate the classical Holmes
      retinotopic map by using the data obtained from comparing visual field
      abnormalities with degree of visual cortex atrophy. METHODS: MR imaging was
      performed in eight patients with Minamata disease who had been given a full
      neuroophthalmic examination, including Goldmann dynamic perimetry. The atrophic
      portions of the calcarine area were measured in the sagittal plane next to the
      midsagittal image and represented as a percentage of atrophy of the total length
      of the calcarine fissure. MR findings were compared with results of a visual
      field test. RESULTS: The visual field test revealed moderate to severe concentric
      constriction of the visual fields, with central vision ranging from 7 degrees to
      42 degrees (mean, 19 degrees). The ventral portion of the calcarine sulcus was
      significantly dilated on MR images in all patients. A logarithmic correlation was
      found between the visual field defect and the extent of dilatation of the
      calcarine fissure. The central 10 degrees and 30 degrees of vision seemed to fill
      about 20% and 50% of the total surface area of the calcarine cortex,
      respectively. CONCLUSION: Visual field deficits in patients with Minamata disease
      correlated well with MR findings of the striate cortex. Our data were consistent
      with the classical Holmes retinotopic map.

PMID- 9194442
TI  - Focal cortical dysplasia of Taylor, balloon cell subtype: MR differentiation from
      low-grade tumors.
AB  - PURPOSE: To test the hypothesis that focal cortical dysplasia of Taylor (FCDT)
      can be distinguished from low-grade tumors by means of clinical and MR findings.
      METHODS: We examined 10 clinical and 19 MR imaging variables in patients who
      underwent surgery for intractable epilepsy over an 8-year period. The 54 patients
      with low-grade glial neoplasms were compared with the eight patients who had
      balloon cell FCDT. RESULTS: Statistically significant differences were seen with
      respect to eight of the MR variables and none of the clinical variables. MR
      findings suggesting dysplasia rather than tumor included the presence of gray
      matter thickening associated with a homogeneous hyperintense signal in the
      subcortical white matter that tapers as it extends to the lateral ventricle. A
      frontal lobe location favors dysplasia, while a temporal lobe (especially medial
      temporal lobe) location is more suggestive of a neoplasm. CONCLUSION: Several MR
      features help distinguish balloon cell FCDT from neoplasms, especially cortical
      thickening and a tapered signal to the ventricle. This distinction is important
      for surgical planning, as the decision to operate and the extent of surgical
      resection often depend on the presence or absence of neoplastic tissue.

PMID- 9194443
TI  - Assessment of whole-brain vasodilatory capacity with acetazolamide challenge at
      1.5 T using dynamic contrast imaging with frequency-shifted burst.
AB  - PURPOSE: To determine whether whole-brain acetazolamide-induced changes in
      regional cerebral blood volume (rCBV) can be assessed on a conventional gradient
      1.5-T MR system using 3-D dynamic susceptibility contrast-enhanced MR imaging.
      METHODS: A 3-D frequency-shifted (FS) burst technique was used to assess the
      intravascular first pass of contrast agent. Changes in rCBV were calculated in 40
      volunteers before and after acetazolamide (n = 30) or saline (n = 10) injection
      using customized analysis software on an independent workstation. A single
      section gradient-echo technique with better spatial resolution was used in one
      additional volunteer to examine the effect of partial volume averaging on
      calculation of absolute rCBV. RESULTS: A statistically significant increase in
      rCBV (gray matter = 23%, white master = 32.5%) was noted after acetazolamide
      compared with saline. Baseline fractional CBVs were 22% +/- 3% for gray matter
      and 12% +/- 2% for white matter. Partial volume averaging was probably
      responsible for a systematic but linear overestimation of absolute rCBV.
      CONCLUSION: Acetazolamide-induced changes in rCBV can be assessed using 3-D
      dynamic susceptibility contrast-enhanced MR imaging with FS-burst on a
      conventional gradient 1.5-T MR system. Values obtained with this technique
      overestimate absolute rCBV but are systematically biased and can be used for
      intersubject and intrasubject ratio comparisons.

PMID- 9194444
TI  - MR of Zellweger syndrome.
AB  - PURPOSE: To determine characteristic MR imaging features of Zellweger syndrome.
      METHODS: Clinical records, laboratory records, and MR studies of six patients
      with Zellweger syndrome were reviewed retrospectively. MR studies were examined
      for the state of myelination; the presence, extent, and morphologic appearance of
      cerebral cortical anomalies; the status of the cerebellar cortex, basal nuclei,
      and brain stem; and the presence or absence of any regions of abnormal signal
      intensity. RESULTS: The diagnosis of Zellweger syndrome was established in all
      patients by clinical findings combined with laboratory and MR results. All
      patients had impaired myelination and diffusely abnormal cortical gyral patterns
      that consisted of regions of microgyria (primarily in the frontal and perisylvian
      cortex) together with regions of thickened pachygyric cortex (primarily
      perirolandic and occipital). The pachygyric regions were in the form of deep
      cortical infoldings. Germinolytic cysts were visible in the caudothalamic groove
      in all patients, seen best on coronal or sagittal T1-weighted images. One patient
      had T1 shortening in the bilateral globus pallidus, presumably related to hepatic
      dysfunction and hyperbilirubinemia. CONCLUSION: The combination of
      hypomyelination, cortical malformations that are most severe in the perisylvian
      and perirolandic regions, and germinolytic cysts are highly suggestive of
      Zellweger syndrome in the proper clinical setting.

PMID- 9194445
TI  - Radiologic-clinical correlation. Junctional visual field loss.

PMID- 9194446
TI  - Central neurocytoma with clinically malignant behavior.
AB  - We describe two cases of central neurocytoma that did not show histopathologic
      features of anaplasia but did show tumor dissemination after surgery and
      radiation therapy. CT and MR imaging before surgery depicted extraventricular
      extension of the tumors. The importance of radiologic findings is stressed.

PMID- 9194447
TI  - Extraaxial ependymoma of the posterior fossa.
AB  - We report an unusual case of an extraaxial ependymoma of the posterior fossa in
      an adult. MR imaging showed a heterogeneously enhancing extraaxial mass with a
      cystic component. Ependymoma should be included in the differential diagnosis of
      uncommon extraaxial masses of the posterior fossa.

PMID- 9194448
TI  - Cystic pituitary mass in neurosarcoidosis.
AB  - An MR examination in a patient with neurosarcoidosis showed an intrasellar cystic
      mass extending into the suprasellar space. The wall of the mass was thick, it
      enhanced after administration of contrast material, and it extended into the
      infundibulum and hypothalamus. Pathologic findings showed noncaseating
      granulomatous inflammation; the cystic component was considered to be ischemic
      necrosis of the intracranial sarcoid mass.

PMID- 9194449
TI  - Transient obstruction of the internal carotid artery during angiography.
AB  - While performing carotid angiography in a 76-year-old man, we found that the
      right internal carotid artery repeatedly opened and closed during the
      examination. The patient experienced no related neurologic events. The
      explanation, confirmed at surgery, was that a flap associated with an
      atherosclerotic plaque had acted as a ball valve.

PMID- 9194450
TI  - MR changes in transverse myelitis.

PMID- 9194451
TI  - MR changes in transverse myelitis.

PMID- 9194452
TI  - Vertebral vein imaging with MR angiography.

PMID- 9194453
TI  - Hippocampal atrophy as detected by width of the temporal horn is greater in
      Alzheimer dementia than in nondementing cognitive impairment.

PMID- 9194454
TI  - Generations of Guglielmi detachable coils.

PMID- 9194455
TI  - Annotated bibliography.

PMID- 9194456
TI  - Variations in treatment of rectal cancer: the influence of hospital type and
      caseload.
AB  - PURPOSE: Surgical options for the treatment of rectal cancer may involve
      sphincter-sparing procedures (SSP) or abdominoperineal resection (APR). We sought
      to examine variations in the surgical treatment of rectal cancer for a large,
      well-defined patient population and specifically to determine if differences
      exist in management and survival based on hospital type and surgical caseload.
      METHODS: The Cancer Surveillance Program database for Los Angeles County was used
      to retrospectively retrieve data on all patients who underwent SSP or APR for
      rectal adenocarcinoma between 1988 and 1992. RESULTS: A total of 2,006 patients
      with adenocarcinoma of the rectum underwent SSP or APR during the study period.
      Overall, 55 percent underwent SSP, and the remaining 45 percent underwent APR.
      Use of SSP remained relatively constant for each year of the five-year period.
      Substantial variability was seen in the use of SSP at various hospital types. For
      localized disease, this varied from as low as 52 percent at teaching hospitals to
      as high as 78 percent at hospitals approved by the American College of Surgeons
      (P = 0.067). To examine the role of caseload experience, hospitals were divided
      into those completing an average of five or fewer rectal cancer cases per year
      vs. those completing an average of more than five cases per year. For localized
      disease, hospitals with higher caseloads performed SSP in significantly more
      cases, 69 vs. 63 percent (P = 0.049). Survival was seen to be significantly
      improved for patients operated on at hospitals with higher caseloads, in cases of
      both localized and regional diseases (P < 0.001). CONCLUSION: Surgical choices in
      the treatment of rectal cancer may vary widely, even in a well-defined geographic
      region. Although the reasons for this variability are multifactorial, hospital
      environment and surgical caseload experience seem to have a significant role in
      the choice of surgical procedure and on survival.

PMID- 9194457
TI  - Outcome of the pelvic pouch procedure in patients with prior perianal disease.
AB  - PURPOSE: There is concern that patients with presumed ulcerative colitis and
      significant perianal disease may in fact have Crohn's disease. Moreover, prior
      perianal disease may be an independent factor for poor outcome of the pelvic
      pouch. The aim of this study was to evaluate the effect of prior perianal disease
      on pelvic pouch outcome. METHODS: Between 1982 and 1994, 52 of 753 patients (6.9
      percent) who had a pelvic pouch procedure were prospectively identified as having
      perianal disease. Outcome of the pelvic pouch of these 52 patients (Group I) were
      compared with the outcome of 701 pelvic pouch patients with no prior perianal
      disease (Group II). The perianal diseases identified in Group I were fissure-in
      ano (17), perianal abscesses (13), fistula-in-ano (7), rectovaginal fistula (3),
      and significant hemorrhoids/skin tags (25). Eleven patients (21 percent) had more
      than one type of perianal disease. Twenty-seven patients (52 percent) required a
      total of 33 perianal operations for the different anal pathologies. RESULTS: Both
      groups were comparable for the following characteristics: age at time of pelvic
      pouch procedure, pathology (ulcerative colitis or indeterminate colitis), design
      of pouch, and type of ileoanal anastomosis (handsewn or stapled). An ileoanal
      anastomosis leak developed in 21 percent of patients (n = 11) in Group I vs. 11.4
      percent (n = 80) in Group II (P < 0.05). Perianal postoperative complications
      occurred in 11.5 percent of patients (n = 6) in Group I vs. 1.7 percent (n = 12)
      in Group II (P < 0.05). Total pouch failure rate was not significantly different
      between the two groups (11.5 vs. 7.6 percent; P > 0.05). Crohn's disease was
      subsequently diagnosed in 1.9 vs. 2.7 percent (P > 0.05). Subgroup analysis of
      Group I patients showed no significant difference in outcome according to type of
      perianal lesion or a history of perianal surgery. CONCLUSION: Prior perianal
      disease significantly increases the risk of developing an ileoanal anastomotic
      leak and postoperative perianal complications. However, a pelvic pouch procedure
      may be an acceptable surgical alternative for selected ulcerative colitis
      patients with prior perianal disease because the overall pouch failure rate is
      not significantly increased.

PMID- 9194458
TI  - Extent of smooth muscle resection during mucosectomy and ileal pouch-anal
      anastomosis affects anorectal physiology and functional outcome.
AB  - PURPOSE: In patients undergoing colectomy with ileal pouch-anal anastomosis,
      controversy exists regarding the necessity for and appropriate extent of rectal
      mucosal resection. Our aim was to assess histologically the extent of anorectal
      smooth muscle resected at the time of mucosal proctectomy and to correlate this
      with postoperative bowel and anal sphincter function. METHODS: Surgical specimens
      of 79 patients undergoing colectomy, mucosal proctectomy, and ileal pouch-anal
      anastomosis were examined histologically in a blinded fashion, and the content of
      smooth muscle in the mucosal proctectomy specimens was scored. Degree of smooth
      muscle resection was correlated with postoperative anorectal manometry and with
      functional outcomes, including stool frequency and nocturnal leakage of stool
      after 3 and 12 months of follow-up. RESULTS: Degree of smooth muscle loss
      correlated with decreased resting pressure of the internal anal sphincter as
      early as three months after surgery (r = -0.26; P = 0.03), and the correlation
      was even stronger after 12 months (r = -0.37; P = 0.005). Decreases in resting
      pressure were related, in turn, to increased stool frequency at 12 months (r =
      0.32; P = 0.02), but stool frequency was also inversely related to volume of the
      ileal pouch (r = -0.27; P = 0.05). Multivariate analysis confirmed that resting
      pressure and pouch volume were both significant determinants of stool frequency.
      The likelihood of nocturnal stool leakage at 12 months was primarily a function
      of stool frequency (P < 0.01) but also increased with patient age (P < 0.02).
      CONCLUSIONS: These findings indicate that loss of resting pressure of the
      internal anal sphincter can be correlated with the extent of smooth muscle
      resection during rectal mucosectomy and that these factors, in turn, correlate
      with increased stool frequency and a greater likelihood of nocturnal stool
      leakage. Consequently, an optimum functional result requires care in identifying
      and preserving maximum anorectal smooth muscle during mucosectomy.

PMID- 9194459
TI  - Anorectal melanoma--an incurable disease?
AB  - PURPOSE: This study was designed to describe recurrence and survival rates after
      operative treatment for anorectal melanoma and to identify predictive factors for
      recurrence. METHODS: Records of 50 patients with anorectal melanoma from 1939 to
      1993 were reviewed. RESULTS: Overall five-year survival and disease-free survival
      were 22 and 16 percent, respectively. At the time of diagnosis, 26 percent of
      patients had metastatic disease, and all died within 12 (mean, 6.3) months. Five
      year survival and recurrence rates were identical after either abdominoperineal
      resection (APR) or wide local excision, both with curative intent. Gender, size
      of tumor, presence of melanin, positive perirectal lymph nodes, or treatment were
      not predictive of recurrence. Anorectal melanoma was found incidentally after
      hemorrhoidectomy or polypectomy in five patients. Three other patients underwent
      an excisional biopsy of a lesion measuring less than 2 cm. Of these eight
      patients, five underwent APR and three underwent wide local excision with no
      microscopic residual tumor at pathology. All developed regional or systemic
      recurrence at a mean of 21 (range, 4-88) months, and all died of their disease at
      a mean of 29 (range, 5-98) months. CONCLUSION: Prognosis for anorectal melanoma
      is poor, irrespective of surgical treatment performed. No predictive factors for
      recurrence were identified in this series. Wide local excision with a negative
      margin of a least 1 cm is suggested as the treatment of choice. APR should be
      reserved for tumor not amenable to local excision or for palliative treatment of
      large obstructive lesion until effective adjuvant therapies are available.

PMID- 9194460
TI  - Intraoperative colonic lavage in nonelective surgery for diverticular disease.
AB  - BACKGROUND: Staged resection of the sigmoid colon has been the traditional
      strategy for treating patients who require nonelective surgery to manage
      complications of diverticular disease. Resection and primary anastomosis has not
      generally been recommended when the clinical setting is compromised by contiguous
      inflammation or inadequate mechanical cleansing of the colon because of concerns
      regarding the potential risk of anastomotic dehiscence. Although many reports
      have confirmed that intraoperative colonic lavage (ICL) is a safe method for
      relieving fecal loading of the colon to facilitate primary intestinal anastomosis
      in patients with mechanical obstruction of the distal colon, there is very
      limited experience with the use of this technique in treating acute inflammatory
      disorders of the colon. In this report, we present our results with ICL in the
      nonelective treatment of patients with complications of diverticulitis. METHODS:
      Records of all patients undergoing urgent operations at the Lahey Clinic to treat
      complications of diverticular disease from July 1987 to January 1996 were
      reviewed. RESULTS: Of 62 patients who required nonelective operations, 33
      underwent ICL in an attempt to perform primary anastomosis. In five patients, the
      operation included creation of a colostomy. The indication for surgery was
      obstruction in 13 patients (39 percent), persistent abscess or phlegmon in 13 (39
      percent), perforation in 6 patients (18 percent), and hemorrhage in 1 patient (3
      percent). According to Hinchey's classification system, 18 patients had Stage I
      disease, 10 had Stage II, and 5 patients had Stage III disease. There were no
      patients with Stage IV disease. The single anastomotic complication in the series
      was responsible for the sole operative mortality. The morbidity rate of 42
      percent, included three intraoperative complications (2 splenic injuries and 1
      ureteral laceration), two intra-abdominal abscesses (6 percent), and six wound
      infections (18 percent). CONCLUSION: In our experience, ICL has proven to be a
      safe method for accomplishing single-stage resection of the colon in selected
      patients with diverticulitis who require an urgent operation. When there is no
      evidence of diffuse purulent or feculent peritonitis, we believe this is the
      preferred method for treating patients who are hemodynamically stable.

PMID- 9194461
TI  - Laparoscopic total abdominal colectomy with ileorectal anastomosis for familial
      adenomatous polyposis.
AB  - PURPOSE: This study was undertaken to describe our results in a series of
      patients undergoing total abdominal colectomy with ileorectal anastomosis
      (TAC/IRA) using laparoscopic techniques in patients with familial adenomatous
      polyposis (FAP) and rectal-sparing. Young patients with FAP requiring TAC/IRA may
      be ideal candidates for minimally invasive surgery, because they are generally
      thin and have benign disease. They might benefit maximally from the theoretic
      advantages of these techniques. METHODS: We have performed laparoscopic TAC/IRA
      in 16 FAP patients (10 females; mean age, 18 years). Procedures were entirely
      intracorporeal, with a 3-cm to 6-cm specimen extraction incision. RESULTS: Median
      operative time was 232 (range, 156-285) minutes, and blood loss 175 (range, 50
      675) ml. The only intraoperative complication, a twisted ileorectal anastomosis,
      was noted intraoperatively and revised. There were no conversions to conventional
      laparotomy. Median postoperative interval to passage of flatus was three days,
      and for bowel movements it was three days. Median hospital stay was five days.
      One case of early postoperative small-bowel obstruction was treated
      nonoperatively, and one case of brachial plexus neuropraxia resolved
      spontaneously. CONCLUSIONS: Based on this preliminary experience, we believe
      laparoscopic TAC/IRA can be a safe and effective treatment for selected patients
      with FAP. As techniques and instrumentation for laparoscopic colon surgery are
      perfected, this procedure will likely become an appealing option in the
      management of patients with FAP.

PMID- 9194462
TI  - Results of a thirty-year study of familial adenomatous polyposis coli.
AB  - PURPOSE: This study was designed to estimate the efficiency of the various
      methods used to treat familial adenomatous polyposis coli. METHODS: Three hundred
      ninety patients (219 males) underwent surgery for familial adenomatous polyposis
      coli; postoperative follow-up was from 1 to 30 years. RESULTS: Coloproctectomy
      with preservation of the anal sphincter and coloproctectomy with ileoanal pull
      through procedures resulted in development of anal canal cancer in 3 (4.1
      percent) of 74 patients. Follow-up revealed development of cancer in the large
      bowel in 26 (10.7 percent) of 242 patients, in whom colectomy with preservation
      of various colonic segments was performed. CONCLUSIONS: The occurrence rate of
      cancer is not significantly related to patients' gender, age, length of preserved
      colonic segment, presence of cancer in the removed colonic segment, or
      postoperative follow-up period; however, presence of polyps in the colonic
      segments preserved during surgery significantly increased the risk of development
      of cancer at a later time.

PMID- 9194463
TI  - Civilian colon trauma: factors that predict success by primary repair.
AB  - BACKGROUND: Primary repair has become the most common method of treatment for
      civilian injuries of the colon. However, colostomy may still be required in
      selected patients. AIMS: This study was undertaken to identify factors for the
      performance of colostomy in patients with colon injuries. METHODS: During a 60
      month period, all penetrating injuries to the colon treated at Saint Louis
      University Hospital were evaluated. All patients underwent an operation within
      six hours of injury. Rectal injuries were excluded. RESULTS: One hundred thirty
      consecutive patients with injuries to the colon were identified. Primary repair
      was performed in 81 patients (62 percent). Fecal diversion was used in 49
      patients (38 percent). No deaths occurred related to colon injury. Complications
      related to colon injury included wound infections in 22 patients (17 percent) and
      intra-abdominal complications in 16 patients (abscess, 14; fecal fistula, 1).
      Wound complications were most closely related to whether the skin was closed
      primarily or left open (22 vs. 8 percent). Intra-abdominal complications occurred
      in 7 percent of patients in whom the colon injury was closed primarily and in 20
      percent of patients in whom a stoma was created (P > 0.05). Patients chosen for
      colostomy had significantly greater blood loss, more associated injuries, and
      higher scores on the Abdominal Trauma Index (ATI) and Colon Injury Scale (CIS)
      and were more likely to have gross contamination (P < 0.05). Stepwise regression
      analysis of 13 factors revealed that only gross contamination and ATI predicted
      the occurrence of intra-abdominal complications and that CIS most closely
      predicted either wound or intra-abdominal complications. Stratification of
      patients based on an ATI of > or =30 and a CIS of > or =4 revealed no difference
      in outcome between primary repair and colostomy in either the low-risk or high
      risk groups. However, severity of injury was greater in patients treated with
      colostomy. CONCLUSIONS: Primary repair can be accomplished with low morbidity in
      the majority of civilians with penetrating injuries to the colon. Colostomy may
      be required in high-risk patients as defined by an ATI of > or =30 in association
      with a CIS of > or =4.

PMID- 9194464
TI  - Effect of radiotherapy on anorectal function in patients with cervical cancer.
AB  - PURPOSE: The acute and long-term effects of pelvic radiation on defecation were
      studied. METHOD: Anorectal function was assessed based on manometry and
      subjective symptoms in 31 patients with cervical cancer treated by radiotherapy
      alone. Sixteen of 31 patients were examined periodically before, during, and
      after radiotherapy (early group). Fifteen others were examined more than six
      months after completion of radiotherapy (late group). RESULTS: One-third of
      patients in both groups had symptoms, mainly diarrhea and increased stool
      frequency. Patients in the late group also suffered from disturbed gas-stool
      discrimination, urgency, a sense of residual stool, and soiling. Anal canal
      resting pressure was significantly higher after radiotherapy (47 +/- 15.5 mmHg)
      than before radiotherapy (36.3 +/- 12.5 mmHg; P < 0.05). The maximum tolerable
      volume decreased with radiation, from 163.3 +/- 45 before to 119.2 +/- 41.4 ml
      during, 112.7 +/- 36.6 ml immediately after, and 94.6 +/- 34.4 ml in the late
      group (P < 0.01). Rectal compliance also decreased over time and was lower in the
      early group (before, 5.7 +/- 1.3 ml/mmHg; P < 0.01; during, 4.6 +/- 2.2 ml/mmHg,
      P < 0.01; after, 3.7 +/- 1.4 ml/mmHg; P < 0.05) than the late group (2.1 +/- 1.5
      ml/mmHg) and lower before than after in the early group (P < 0.01). Although
      rectal pressure initiating continuous desire to defecate did not change, the
      maximum tolerable pressure was significantly higher in the late group (81 +/-
      19.5 mmHg) than during (59 +/- 16.8 mmHg) or after (59.9 +/- 16.9 mmHg)
      radiotherapy in the early group (P < 0.05). CONCLUSION: Radiation reduces the
      capacity of the rectal reservoir, even in asymptomatic patients. These changes
      develop during radiotherapy and progress over time.

PMID- 9194465
TI  - Total anorectal reconstruction with a double dynamic graciloplasty after
      abdominoperineal reconstruction for low rectal cancer.
AB  - PURPOSE: Total anorectal reconstruction with a double dynamic graciloplasty was
      performed after abdominoperineal reconstruction (APR) for low rectal cancer. In
      four patients an additional pouch was constructed to improve neorectal motility
      and capacity. The aim of this study was to evaluate the results in the first 20
      patients and to report on the preliminary results of patients with an additional
      pouch. METHODS: Twenty patients with a mean age of 52 (range, 25-71) years and a
      rectal tumor at a mean of 3 (range, 0-5) cm from the anal verge were treated. In
      14 patients the Miles resection, colon pull-through, and construction of a
      neosphincter were performed in one session. Six patients had the double
      graciloplasty at an average of 4.1 (range, 1.1-8.8) years after APR. In four
      patients a pouch was constructed with an isolated segment of distal ileum.
      RESULTS: After a mean follow-up of 24 (range, 1-60) months after APR, none of the
      patients developed local recurrence, whereas four patients developed distant
      metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients
      were still in training. Of these 15 patients, 8 patients were continent (53
      percent), 2 patients were incontinent, and in 5 patients the perineal stoma was
      converted to an abdominal stoma. Failures were attributable to necrosis of the
      colon stump (n = 2) and incontinence (n = 3). At 26 weeks mean resting pressure
      was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation
      was 90 (SD, 46) mmHg at a mean of 3.5 (SD, 1.2) volts at 52 weeks. Mean
      defecation frequency was three times per day (range, 1-5). Of the eight patients
      who were continent, six used daily enemas. Mean time to postpone defecation was
      11 (range, 0-30) minutes. CONCLUSION: In experienced hands, the double dynamic
      graciloplasty is an oncologically safe procedure that can have an acceptable
      functional outcome in a well-selected group of patients. However, to improve the
      outcome, further modifications will be necessary. So far, the addition of a pouch
      has not resulted in improved outcome.

PMID- 9194466
TI  - Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth
      muscle.
AB  - PURPOSE: This study was designed to investigate the role of nitric oxide in
      neurogenic relaxation of the longitudinal layer of human rectal smooth muscle.
      METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior
      resection for carcinoma. Adjacent strips of longitudinal muscle were dissected
      and mounted in organ baths for isometric tension recording. In preliminary
      experiments to determine the response of strips to cholinergic, adrenergic, and
      potential excitatory agonists, strips were superfused with standard Krebs
      solution (37 +/- 0.5 degrees C; pH, 7.4 +/- 0.05). Investigation of inhibitory,
      nonadrenergic noncholinergic responses required the addition of 3 x 10(-6) M
      histamine to induce reproducible and stable tension for five-minute "test"
      periods, during which electrical field stimulation (EFS) and additional drugs
      were applied. In these experiments, strips were superfused with Krebs solution
      that contained atropine sulfate (3 x 10(-6) M) and guanethidine (3 x 10(-6) M).
      RESULTS: The response to cholinergic and adrenergic agonists was typical of
      nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency
      dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted
      strips, which were reduced in dose-dependent fashion by addition of N omega-nitro
      L-arginine and restored by addition of 3 x 10(-4) M L-arginine but not by D
      arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the
      relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal
      layer of human rectum receives an intrinsic inhibitory innervation mediated by
      nitric oxide.

PMID- 9194467
TI  - Assessment of a novel implantable artificial anal sphincter.
AB  - PURPOSE: The aim of the study was to test a new implantable artificial anal
      sphincter in the porcine model. METHOD: The artificial sphincter, which includes
      an inflatable expander that compresses and flattens the bowel against a pillow,
      was implanted in 16 animals and studied for periods of up to 20 weeks. The anal
      sphincters were destroyed, and the efficacy of the device in rendering the
      animals continent was studied. RESULTS: Of the 11 animals in which the artificial
      sphincter was regularly closed, 8 completed the study and were continent during
      85 percent of activation times. There was no evidence of ischemic injury. Major
      complications were related only to failure of the control pumps of the device.
      CONCLUSION: This study suggests that this neosphincter produces fecal continence
      without intestinal ischemia. At present reliability is limited only by the
      performance of the pump.

PMID- 9194468
TI  - Substance P containing nerve fibers in rectal mucosa of ulcerative colitis.
AB  - BACKGROUND AND PURPOSE: The intestine is rich in peptidergic innervation, which
      modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has
      received considerable attention for stimulatory effects on various immunocytes in
      inflammatory diseases. In our prior study, we demonstrated increased innervation
      of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC)
      surgically resected colonic specimens. In the present study, we examined the
      alterations of SubP fibers among various subgroups of UC, divided according to
      clinicopathologic features. METHODS: Distribution of SubP fibers were examined
      immunohistochemically in the rectal biopsy specimens of UC. The UC group was
      further divided into subgroups according to six clinicopathologic parameters. The
      linear density of SubP fibers was measured by digitalized morphometry for
      quantitative analysis. RESULTS: Multivariate analysis revealed significant
      correlations between linear density of SubP fibers vs. activity of diseases and
      total dose of prednisolone. Linear density was significantly increased in active
      cases of UC (active UC, 22.6 +/- 1.6 microm/1,000 microm2; vs. inactive UC, 12.2
      +/- 0.8 microm/1,000 microm2; P < 0.01). Furthermore, the increase was pronounced
      in cases that showed persistent inflammation and, accordingly, needed a high dose
      or continuous administration of prednisolone. CONCLUSION: Alterations in SubP
      fibers appear to play an important role in the pathogenesis of UC.

PMID- 9194470
TI  - Double seton--a new modified approach to high transsphincteric anal fistula.
AB  - Despite the fact that complicated extrasphincteric anal fistulas have been
      recognized and treated for many years, there is still a lack of consensus among
      colorectal surgeons as to the optimum surgical approach. We have devised a
      modification of the seton technique, which we used in 23 patients without
      complications or recurrence.

PMID- 9194471
TI  - Colorectal surgery as a specialty.

PMID- 9194469
TI  - Neoplasia in ileal pouch mucosa after total proctocolectomy for juvenile
      polyposis: report of a case.
AB  - PURPOSE: Patients treated with restorative proctocolectomy for familial
      adenomatous polyposis or ulcerative colitis occasionally develop disease in the
      ileal pouch similar to that originally present in the colon. We investigated the
      possibility of analogous involvement in the ileal pouch of juvenile polyposis
      patients. METHODS: Endoscopic surveillance for neoplasia throughout the
      gastrointestinal tract was performed, with retrieval of all polypectomy specimens
      for histologic classification using the criteria of Morson. RESULTS: Multiple
      large juvenile polyps were found in the ileal pouch of one patient less than 10
      years after restorative proctocolectomy for hereditary juvenile polyposis. The
      pouch was much more severely affected than the proximal ileum, small intestine,
      or stomach. Although most polyps had a completely benign histologic appearance,
      three had moderate to severe dysplasia. DISCUSSION: Mucosal changes induced by
      bacteria or stasis of luminal contents may promote manifestation in the ileal
      pouch of the disease phenotype usually more evident in the colon. Patients with
      severe or generalized juvenile polyposis should be considered for periodic
      endoscopic surveillance of the ileal pouch beginning several years after
      restorative proctocolectomy.

PMID- 9194472
TI  - The emerging role of gemcitabine in lung cancer: part I.

PMID- 9194473
TI  - Preclinical, pharmacologic, and phase I studies of gemcitabine.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue that
      exerts its antitumor activity via multiple mechanisms of action. These include
      (1) incorporation of gemcitabine into replicating DNA, which inhibits DNA
      replication and cell growth, (2) masked DNA chain termination, and (3) several
      self-potentiation mechanisms that serve to increase intracellular levels of the
      active compound. Preclinical experiments in various cell lines and animal models
      demonstrate a broad range of cytotoxic activity. Pharmacokinetic studies of
      gemcitabine delivered by its usual schedule (30-minute weekly infusion) reveal a
      short plasma half-life and a high clearance into central and peripheral
      compartments (two-compartment model). The drug is excreted almost completely in
      the urine as the parent compound and primary metabolite (difluorodeoxyuridine).
      Phase I trials demonstrate that pharmacokinetics are schedule dependent and that,
      in general, gemcitabine is well tolerated. Dose-limiting toxicities are primarily
      myelosuppression, with other toxicities being rash, flu-like symptoms, and
      transient elevations in liver function tests.

PMID- 9194474
TI  - In vitro interaction between gemcitabine and other anticancer drugs using a novel
      three-dimensional model.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a deoxycytidine analog with
      significant antitumor activity against ovarian cancer and non-small cell lung
      cancer. It is a suitable candidate for combination chemotherapy in non-small cell
      lung cancer for three reasons: it is active as a single agent, it has no
      overlapping toxicities with other chemotherapeutic agents, and it has different
      mechanisms of action compared with other anticancer drugs. We therefore
      investigated the combination effects between gemcitabine and other anticancer
      drugs on the growth of the non-small cell lung cancer cell line, PC-14.
      Combination effects were analyzed by means of a three-dimensional model, which
      directly elucidates the shape of the dose-response surface over the entire
      clinical dose range, identifies regions of statistically significant synergy and
      antagonism, and quantifies these effects. The three-dimensional analysis clearly
      demonstrates a relationship, the nature of which depends on the concentration of
      both drugs. A synergistic effect was observed when gemcitabine and cisplatin were
      combined at concentrations of 0.0005 to 0.001 microg/mL and 0.025 to 0.25
      microg/mL, respectively. In combination with vindesine, a remarkable synergistic
      interaction also was found when combined at concentrations of 0.00005 to 0.0005
      microg/mL gemcitabine and 0.001 to 0.01 microg/mL vindesine. These results
      suggest the usefulness of combination therapy with gemcitabine/cisplatin and
      gemcitabine/vindesine. However, because these combination effects depend on drug
      concentrations, this parameter must be carefully considered when using such drug
      combinations in clinical applications.

PMID- 9194476
TI  - Gemcitabine-mediated radiosensitization.
AB  - Gemcitabine is a potent radiosensitizer of human tumor cells. This review
      summarizes our preclinical and early clinical studies designed to elucidate the
      mechanism of action of gemcitabine and phase I trials conducted to determine the
      optimal dose and schedule. Gemcitabine was found to radiosensitize a wide variety
      of human tumor cells in culture, particularly cells derived from cancers of the
      pancreas, breast, and head and neck. Radiosensitization occurs under conditions
      in which cells demonstrate concurrent redistribution into S phase and
      deoxyadenosine triphosphate pool depletion. These conditions can be produced by
      either a long (24-hour) exposure to a low concentration of gemcitabine (10
      nmol/L) or by a brief (2-hour) treatment with higher but clinically relevant
      concentrations (100 nmol/L to 3 micromol/L). Under the latter conditions,
      sensitization can be detected 4 hours after treatment and last for up to 2 days.
      These preclinical data were useful in the design of a gemcitabine dose escalation
      trial in combination with standard radiation for patients with unresectable head
      and neck cancer. Although this trial is not yet complete, the starting dose of
      gemcitabine, which is far below the maximum tolerated dose for the drug when used
      alone, significantly potentiates the toxicity of radiation treatment. We conclude
      that gemcitabine is a promising radiation sensitizer that needs to be developed
      cautiously if excessive normal tissue toxicity is to be avoided.

PMID- 9194475
TI  - Combination chemotherapy studies with gemcitabine.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with
      clinical activity against ovarian carcinoma, small cell and non-small cell lung
      cancers, head and neck cancer, bladder cancer, breast cancer, and pancreatic
      cancer. Cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC) are well-known
      anticancer agents that are also active against many of these types of cancer.
      Because of the low toxicity profile of gemcitabine and the differences in
      mechanism of cytotoxicity, combinations of these drugs with gemcitabine were
      studied in vitro and in vivo. Cells were exposed in vitro for 1, 4, 24, or 72
      hours to gemcitabine in combination with these drugs, either simultaneously or
      sequentially in a constant ratio. Another approach consisted of exposure to a
      combination of the approximate IC25 of one drug and varying concentrations of the
      other drug. Synergism for several of these combinations was found in the human
      ovarian cancer cell line A2780, its CDDP-resistant variant ADDP, its gemcitabine
      resistant variant AG6000, and in the non-small cell lung cancer cell lines H322
      and Lewis lung (LL) after a 72-hour drug treatment. Studies of the possible
      mechanisms of action initially focused on the major metabolic features of each
      drug. CDDP did not enhance the accumulation of gemcitabine triphosphate and
      caused only marginal changes in the extent of DNA double-strand breaks (DSBs)
      induced by gemcitabine in these cell lines. Gemcitabine increased platinum
      accumulation only in the ADDP cell line, but the DNA platination was enhanced in
      the A2780, ADDP, AG6000, and LL cell lines. MMC did not influence the formation
      of DSBs by gemcitabine in the LL cell line. The combination of VP-16 and
      gemcitabine, however, resulted in the formation of more DSBs in this cell line
      than each drug alone. This effect was even more pronounced when cells were
      exposed to VP-16 4 hours before gemcitabine. In vivo, the antitumor activity of a
      combination of 50 mg/kg gemcitabine and 6 mg/kg CDDP was more effective against
      LL tumors than each compound alone. In conclusion, gemcitabine is an attractive
      drug to combine with a wide range of anticancer drugs; synergism is often
      schedule dependent.

PMID- 9194477
TI  - Overview of current and future chemotherapeutic agents in non-small cell lung
      cancer.
AB  - The two-drug regimen consisting of a platinum compound (cisplatin or carboplatin)
      combined with either a vinca alkaloid or a podophyllotoxin has been considered by
      many to be the standard chemotherapy treatment for non-small cell lung cancer
      (NSCLC). Randomized trials with these regimens have demonstrated modest but
      statistically significant increases in survival for patients with stage IV
      disease compared to treatment with best supportive care, and especially for
      selected patients with stage III disease when combined with radiotherapy or
      surgery compared to these treatments alone. Recently, several new compounds with
      promising efficacy and acceptable toxicity profiles have been investigated for
      the treatment of NSCLC, including the taxanes paclitaxel and docetaxel, the novel
      pyrimidine analog gemcitabine, and the topoisomerase inhibitors irinotecan and
      topotecan. Small but significant improvements in response rates and survival have
      been achieved with two-drug combinations, which include several of these new
      agents combined with a platinum-based compound, in patients with advanced NSCLC.
      Modifications of dosing schedules and the use of premedication regimens have
      resulted in better efficacy and more manageable side effects with such
      combinations. These encouraging gains in patients with advanced NSCLC suggest a
      potentially greater impact in patients with early stage disease. Given the
      manageable toxicity profiles of many of these newer agents, various three-drug
      regimens may be feasible in the future.

PMID- 9194478
TI  - Efficacy of single-agent gemcitabine in advanced non-small cell lung cancer: a
      review.
AB  - Within the last 5 years, gemcitabine, a new nucleoside analogue, has been
      evaluated in several international phase II trials in patients with advanced non
      small cell lung cancer (NSCLC). Five trials have evaluated 438 patients.
      Gemcitabine was administered intravenously in four trials on days 1, 8, and 15 at
      a dose of 800 to 1,700 mg/m2 every 4 weeks. In the fifth trial, gemcitabine was
      given at a dose of 90 mg/m2 twice weekly x 3 every 4 weeks. The overall response
      rate was 21% (95% confidence limits, 16% to 25%) with a median survival of 4
      weeks (range, 26 to 46 weeks). The median duration of response varied from 26 to
      49 weeks. The activity of gemcitabine in NSCLC, together with its modest toxicity
      and distinct mode of action, suggest the need for further trials of gemcitabine
      in combination with other chemotherapeutic agents in the treatment of NSCLC.

PMID- 9194479
TI  - Phase II studies of gemcitabine for non-small cell lung cancer in Japan.
AB  - To determine the activity and toxicity of gemcitabine (2',2'
      difluorodeoxycytidine), three phase II single-agent studies have been conducted
      in patients with non-small cell lung cancer in Japan. In an early phase II study,
      17 previously treated and 47 untreated patients were treated with gemcitabine.
      Gemcitabine was given intravenously at a dose of 800 mg/m2 or 1,000 mg/m2 once a
      week for 3 weeks followed by a week of rest, repeating every 4 weeks. Although
      none of the patients with prior therapy responded, eight (17%) of 47 previously
      untreated patients showed a partial response. Toxicities of grade 3 or greater
      included leukopenia (12.5%), thrombocytopenia (6.3%), and anemia (15.6%). We
      entered 73 patients (group A) and 67 patients (group B) into two late phase II
      studies. All patients had no previous chemotherapy and had measurable disease.
      Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks
      followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe
      toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a
      partial response (95% confidence interval, 16.5% to 37.6%) in group A. Of 67
      patients, 14 (20.9%) showed a partial response (95% confidence interval, 11.9% to
      32.6%) in group B. Grade 3 or greater anemia and leukopenia occurred,
      respectively, in 15 (20.5%) and seven (9.6%) patients in group A and in nine
      (13.4%) and seven (10.4%) patients in group B. Grade 3 thrombocytopenia was
      observed in one patient (1.4%). Other toxicities including hepatic toxicity,
      fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity
      was observed in five patients, two of whom died of respiratory insufficiency. The
      median durations of response were 19.6 weeks in group A and 20 weeks in group B,
      and median survival times were 44 and 39 weeks, respectively. In conclusion,
      gemcitabine is an active agent against non-small cell lung cancer with very mild
      toxicities. These results suggest that gemcitabine has potential utility on an
      outpatient basis. Further trials in combination with other active agents are
      warranted.

PMID- 9194480
TI  - Single-agent gemcitabine in non-small cell lung cancer: the French experience.
AB  - Gemcitabine is a novel nucleoside analogue that has demonstrated activity against
      several solid tumors. A large phase II study has been performed in Europe and
      Canada with a total enrollment of 161 non-small cell lung cancer patients, 26 of
      whom were from the Institut Gustave-Roussy. Patient characteristics were the same
      for our patients and the whole study population. One hundred fifty-one patients,
      including 24 at our institution, were evaluable for response. We observed an
      objective response rate of 21.8% (95% confidence interval, 15.5% to 29.3%) and
      median survival of 9.4 months for the whole population (7.5 months at our
      institution), with a 1-year survival rate of 42% (38% at our institution).
      Tolerance was good in the majority of patients. These results suggest that
      gemcitabine can be considered a safe and active agent for the treatment of
      patients with advanced non-small cell lung cancer.

PMID- 9194482
TI  - Cost-effectiveness of gemcitabine in stage IV non-small cell lung cancer: an
      estimate using the Population Health Model lung cancer module.
AB  - Statistics Canada (Ottawa, Ontario, Canada) is in the process of developing the
      Population Health Model to simulate the health and common illnesses of Canadians.
      The Population Health Model incorporates a lung cancer module that is based on
      contemporary Canadian practice. This microsimulation model can be used to
      estimate the total direct care costs of treating all lung cancer cases diagnosed
      in Canada and to evaluate the cost and cost-effectiveness of new therapeutic
      interventions as they are introduced into practice. Gemcitabine, a new nucleoside
      analogue with a broad spectrum of antitumor activity, is about to be introduced
      on the Canadian market. The Population Health Model has been used to estimate the
      cost-effectiveness of gemcitabine in the management of lung cancer over a range
      of drug doses per treatment cycle starting at 1,000 mg/m2 weekly x 3, as well as
      potential survival benefits. The survival of stage IV non-small cell lung cancer
      (NSCLC) patients treated on an international trial of gemcitabine (EO-18) was
      used to estimate the potential survival gain relative to the survival of stage IV
      NSCLC patients managed with best supportive care on a randomized trial conducted
      by the National Cancer Institute of Canada (BR 5). Sensitivity analyses were
      performed assuming that the survival gain was 25% or 50% less than that reported
      in the EO-18 trial. The perspective of the economic analysis is that of the
      government as payer in a universal health care system, and all costs are
      expressed in 1993 Canadian dollars. Based on the apparent survival advantage of
      the EO-18 trial in comparison to best supportive care, the cost per life-year
      gained ranged from $632 to $9,285, depending on the dose per treatment cycle. At
      the highest dose per cycle (2,000 mg/m2) and with survival reduced by 50% as
      compared with the EO-18 result, the cost per life-year gained was estimated to be
      $17,390. From these estimates of direct care costs in the Canadian health care
      system, gemcitabine appears to be a cost-effective intervention for advanced
      NSCLC.

PMID- 9194481
TI  - Gemcitabine in the treatment of elderly patients with advanced non-small cell
      lung cancer.
AB  - Gemcitabine is active against non-small cell lung cancer (NSCLC), with single
      agent response rates of 20% or more in previously untreated patients. Its mild
      toxicity profile suggests that it should be well tolerated by older patients. To
      assess the impact of age on the efficacy and tolerance of gemcitabine, the
      results of four phase II trials of single-agent gemcitabine for the treatment of
      NSCLC were analyzed retrospectively. Starting doses for gemcitabine ranged from
      800 to 1,250 mg/m2/wk, and in all studies gemcitabine was administered weekly for
      3 weeks followed by a 1-week rest period. Response rates, toxicity, and dose
      delivery were compared for two age groups, less than 65 years (255 patients) or >
      or = 65 years (105 patients). The pretreatment characteristics for both patient
      groups were well balanced. Overall response rates were 16% and 24% for the
      younger and older patients, respectively (P = .072). Median survival and 1-year
      survival rates were 8.1 months and 27% and 9.1 months and 36%, respectively, for
      patients aged less than 65 years and > or = 65 years. Hematologic and
      nonhematologic toxicities were similar for both age groups. The number of cycles
      associated with dose reductions or dose omissions and the mean number of
      treatment cycles administered were also similar. In summary, gemcitabine is
      active and well tolerated in elderly patients with NSCLC, and is a promising new
      alternative for the treatment of this patient population.

PMID- 9194483
TI  - Phase I studies of gemcitabine combined with carboplatin or paclitaxel.
AB  - Gemcitabine is a novel nucleoside analogue with a unique mechanism of action. In
      light of its good single-agent activity in several solid tumors, generally mild
      toxicity profile, and potential for synergy, combination phase I studies with
      other active chemotherapeutic agents have been conducted. In two studies the
      combination of gemcitabine and carboplatin was used to treat patients with non
      small cell lung cancer. Gemcitabine was administered weekly x 3 every 4 weeks,
      and carboplatin was given on day 1. Although dose-limiting myelotoxicity was
      observed, encouraging activity was noted. In other studies patients with
      recurrent or persistent ovarian cancer or with refractory solid tumors were
      treated with weekly gemcitabine and paclitaxel on a 28-day schedule or with both
      drugs given every 2 weeks. Dose escalation was possible and toxicities were
      manageable. The effect of sequence of drug administration on the toxicity profile
      was also examined. Further trials to establish the efficacy of these promising
      approaches as well as combinations of all three drugs are needed.

PMID- 9194484
TI  - Overview of chemotherapy for small cell lung cancer.
AB  - Small cell lung cancer (SCLC) accounts for 20% to 25% of all lung cancer cases in
      developing countries. The incidence of and mortality from SCLC continues to
      increase in these countries, especially in females. Small cell lung cancer is
      different from other lung cancer histologic types in that it has neuroendocrine
      features, grows more rapidly, spreads earlier, is more responsive to chemotherapy
      and radiotherapy, and has a lower cure rate. Because of the propensity to
      metastasize early, the lack of screening modalities, and the sensitivity to
      chemotherapy, the cornerstone of treatment is combination chemotherapy, which is
      indicated in all SCLC patients able to tolerate any therapy. Patients with
      extensive-stage SCLC generally receive combination chemotherapy alone. Most
      patients with limited-stage SCLC should be treated with combined modality therapy
      consisting of chemotherapy and chest radiotherapy. In the rare patient with stage
      I SCLC and no involved lymph nodes, surgical resection with chemotherapy provides
      a high rate of long-term survival. Several combinations are used routinely,
      including the two-drug combination of etoposide with cisplatin or carboplatin,
      which is used most frequently in the United States. There is no proven role for
      any type of maintenance therapy, for intensive chemotherapy, or for biological
      therapies. There have been no major advances in therapy in the last decade,
      although the recent advent of new active agents, including gemcitabine, provides
      hope for more effective therapies in future years. This report will review the
      past literature on SCLC therapy.

PMID- 9194485
TI  - Gemcitabine and etoposide in small cell lung cancer: phase I and II trials.
AB  - Gemcitabine and etoposide have both shown single-agent activity against multiple
      tumor types in clinical trials, including small cell lung cancer, but have not
      been previously used together. Forty-four patients with small cell and non-small
      cell lung cancer or other tumor types were enrolled in a phase I dose-finding
      trial using this drug combination. Gemcitabine 1,000 mg/m2 was given
      intravenously on days 1, 8, and 15 of a 28-day cycle, and etoposide (dose
      escalated from 20 to 80 mg/m2) was given on days 8, 9, and 10. Leukopenia,
      thrombocytopenia, and anemia were the major toxicities noted. Objective responses
      were observed in five of 44 patients. The maximum tolerated dose of etoposide was
      determined to be 80 mg/m2. On the basis of these results, a phase II trial of
      gemcitabine and etoposide in patients with small cell lung cancer has been
      initiated. Twelve patients have been enrolled in this ongoing trial, and toxicity
      to date has been manageable.

PMID- 9194486
TI  - Analysis of the Rb gene and cyclin-dependent kinase 4 inhibitor genes (p16INK4
      and p15INK4B) in human ovarian carcinoma cell lines.
AB  - In the present study, we analyzed human ovarian carcinoma cell lines for
      abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin
      dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular
      biology techniques. For the Rb gene, in all six cell lines (PA-1, Caov-3 and -4,
      OVCAR-3, SK-OV-3, and Kuramochi), Rb gene abnormality was not detected using
      Southern blotting. In the Caov-3 cell line transcripts were not detectable by
      either Northern blot or polymerase chain reaction. Sequence analysis of the
      entire coding region of the Rb gene revealed point mutations (AAC to GAC)
      resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell line. In the PA-1
      cell line both wild-type Rb and mutant-type Rb (codon 798: CGG to TGG) were
      expressed, and in the OVCAR-3 cell line both wild-type Rb and mutant-type Rb
      (codon 704: ATG to GTG) were expressed. In four of six human ovarian carcinoma
      cell lines Rb gene abnormality was detected. For the p16INK4 and p15INK4B genes,
      only the SK-OV-3 cell line had abnormalities. There was a gene rearrangement or
      minor deletion of the p16INK4 gene in the SK-OV-3 cell line, while the p15INK4B
      gene was deleted in this cell line. In the SK-OV-3 cell line no mRNAs of p16INK4
      and p15INK4B were expressed. At the point of Rb gene inactivation, we can explain
      five cell lines of six: four cell lines had abnormalities in the Rb gene itself,
      which is another mechanism by which the Rb gene is inactivated, while one cell
      line (SK-OV-3) had abnormalities in CDK4 inhibitor genes, another of the
      inactivation mechanisms of the Rb gene. These data suggest that abnormalities of
      Rb and CDK4 inhibitor genes (p16INK4, p15INK4B) may be involved in human ovarian
      carcinogenesis.

PMID- 9194487
TI  - Dispersed and aggregated gap junction channels identified by immunogold labeling
      of freeze-fractured membranes.
AB  - An indirect immunogold labeling technique was applied to replicas of freeze
      fractured membranes of rapidly frozen unfixed cells. The endogenous gap junction
      protein Cx43 of BICR/M1Rk rat mammary tumor cells was preferentially identified
      in quasi-crystalline gap junction plaques as were the transfected connexins Cx40,
      Cx43, and Cx45 in HeLa (human cervical carcinoma) cells. With this method we also
      detected contact areas with dispersed gap junction channels which are the only
      structural correlation for endogenous Cx45 in HeLa wild-type cells where no gap
      junction plaques exist. In double-transfected HeLa cells a colocalization of Cx40
      and Cx43 was occasionally detected in quasi-crystalline gap junction plaques,
      whereas in contact areas with dispersed particles only one Cx type was present.
      Our results indicate that functional gap junction channels exist outside the
      quasi-crystalline plaques.

PMID- 9194488
TI  - On the mechanics of the first cleavage division of the sea urchin egg.
AB  - We describe a continuum model of the sea urchin egg during the first cleavage
      division. Using estimated values of the relevant mechanical parameters we then
      carry out numerical simulations of cytokinesis and conduct a systematic
      comparison of these computations with a variety of published experimental data.

PMID- 9194489
TI  - Mitochondrial membrane potential changes in osteoblasts treated with parathyroid
      hormone and estradiol.
AB  - This study assessed mitochondrial membrane potential changes in cultured
      osteoblasts treated with hormones known to regulate osteoblasts. A fluorescent
      carbocyanine dye, 5,5',6,6'-tetrachloro-1,1',3,3'
      tetraethylbenzimidazolocarbocyanine++ + iodide, also called JC-1, was used as a
      probe. JC-1 emits photons at 585 nm (orange-red) when the membrane potential in
      mitochondria is highly negative, but when the potential becomes reduced emission
      occurs at 527 nm (green). Osteoblasts were rinsed in serum-free medium for 5 min,
      then loaded with 1 x 10(-6) M JC-1 for 10 min. The distribution and intensity of
      JC-1 fluorescence were evaluated with a laser-scanning confocal microscope
      system. Hormone treatments included parathyroid hormone (PTH; 10(-8) M), 17beta
      estradiol (10(-8) M), and thyroxine (T4; 10(-8) M). The potassium ionophore
      valinomycin (10(-6) M) was used as a control since it is known to disrupt the
      electrochemical gradient of mitochondria without interfering with the pH
      gradient. Valinomycin caused a profound, rapid increase (22.5% above untreated
      values) in the green/red ratio, which indicated a lowering of the mitochondrial
      membrane potential in all samples evaluated. PTH caused a less pronounced, but
      significant (7-14%), reduction in membrane potential in all cells examined. PTH
      is known to affect osteoblasts in a number of ways and is inhibitory to
      mitochondrial respiration; the results confirm this effect. For estradiol, half
      of the cells responded at a significant level, with a membrane potential
      reduction of 6 to 13% being recorded; the other half did not respond. Thyroxine
      did not alter mitochondrial membrane potential. Responses were detectable within
      20 s for valinomycin, but occurred at a slower rate, over 200 to 300 s, following
      PTH and estradiol treatment. Responses to PTH and estradiol could be due to
      mitochondrial uptake of cytosolic Ca2+.

PMID- 9194490
TI  - Altered sensitivity to retinoid-induced apoptosis associated with changes in the
      subcellular distribution of Bcl-2.
AB  - In the acute promyelocytic leukemia cell line NB4, Bcl-2 downregulation occurred
      as a late event of retinoid-induced differentiation. In the maturation-resistant
      NB4-R1 subclone, retinoids failed to downregulate Bcl-2 even in the situation of
      apoptosis massively induced by pan-agonists and RXR-selective agonists. We
      observed that NB4 and NB4-R1 cells differed with respect to the intracellular
      localization of Bcl-2 which showed a perinuclear localization in NB4-R1 cells,
      while Bax was broadly expressed in the cytoplasm and to only a minor extent in
      the perinuclear area. Therefore, the distinct intracellular localization of Bcl-2
      and Bax was in general nonoverlapping. Bcl-2 remained massively expressed until
      cell disruption. Bax was not significantly upregulated in cells committed to
      death. However, Bax localization changed from a diffuse pattern to concentrate in
      few specific cytoplasmic area at a stage preceding the formation of apoptotic
      bodies. A human Bcl-2 transgene was transiently overexpressed in NB4-R1 cells
      which showed increased resistance to apoptosis induced by retinoids. Stably
      transfected clones of NB4-R1 cells showed an increased expression of Bcl-2 and a
      marked resistance to apoptosis. Interestingly, the overexpression of Bcl-2
      restored a pattern of uniform Bcl-2 labeling in the cytoplasm and, remarkably,
      the colocalization of Bcl-2 with Bax. This work demonstrates that the ability of
      retinoid-induced cells to undergo apoptosis depends on the level of expression
      and the functional interaction between Bcl-2 and Bax.

PMID- 9194491
TI  - Characterization of cholesterol-free insect cells infectible by baculoviruses:
      effects of cholesterol on VSV fusion and infectivity and on cytotoxicity induced
      by influenza M2 protein.
AB  - The patented cell line from the cabbage looper Trichoplusia ni (High Five from
      Invitrogen) was found to grow readily under cholesterol-free (CF) culture
      conditions. Cellular cholesterol became undetectable by CF passage 4, while
      growth rate and overall cell morphology remained unaffected for at least 59 CF
      passages. The Golgi apparatus in CF cells was significantly smaller than in
      control cells, and the CF cells also concentrated a ceramide-based fluorescent
      Golgi marker to a greater extent, but endoplasmic reticulum morphology appeared
      unaffected. Two proteins were expressed in High Five cells from recombinant
      baculoviruses under CF and control conditions: the vesicular stomatitis virus
      (VSV) fusion glycoprotein G and the influenza virus ion channel M2. Both proteins
      were expressed in comparable amounts in CF and control cells. Both were properly
      assembled and transported to the plasma membrane in CF cells, indicating the
      presence of functional Golgi. Wild-type G protein expression resulted in
      extensive syncytia formation in both CF and control cells, showing that
      cholesterol is not required for VSV fusion. However, a mutant G protein lacking
      six transmembrane domain residues was inactive in both CF and control cells.
      Influenza M2 protein was functional in control cells, as indicated by its
      amantadine-inhibitable cytotoxicity, but cytotoxicity was absent in CF cells
      expressing this protein, indicating a cholesterol-dependence for the cytotoxic
      action of this protein. CF and control cells were both infectible with VSV.
      However, infected cell centers were modestly decreased (ca. 3.5-fold) in CF
      cells. CF cells offer a convenient and novel approach to the study of specific
      cholesterol functions.

PMID- 9194492
TI  - The calpain-calpastatin system and cellular proliferation and differentiation in
      rodent osteoblastic cells.
AB  - The calpain-calpastatin system, which consists of calpains I and II (two
      ubiquitously distributed calcium-activated papain-like cysteine proteases), as
      well as calpastatin (the endogenous calpain inhibitor), plays an important role
      in cell proliferation and differentiation in many tissues. However, its
      contribution to the regulation of osteoprogenitor or pluripotent stem cell
      proliferation and differentiation into osteoblasts remains poorly defined. In
      these studies, rat pluripotent mesodermal cells (ROB-C26) and mouse MC3T3-E1
      preosteoblasts were induced to differentiate into osteoblasts by long-term
      culture or in response to bone morphogenetic protein (BMP). The occurrence and
      distribution of calpain-calpastatin system proteins were determined by
      immunofluorescent microscopy, measurement of calcium-dependent proteolytic
      activity, and Western blotting. Treatment of intact MC3T3-E1 cells with an
      irreversible, membrane-permeable cysteine protease inhibitor attenuated
      proliferation and alkaline phosphatase upregulation under differentiation
      enhancing conditions. Calpain II activity increased during differentiation of
      MC3T3-E1 cells in postconfluent culture. When ROB-C26 cells were maintained in
      long-term culture, neutral protease, calpain I, and calpain II activities
      increased 2- to 3-fold in the absence of BMP. In the presence of partially
      purified native BMP, neutral protease and calpain I activities also increased
      similarly, but calpain II activity increased by 10-fold in 3 days. The maximal
      increase in alkaline phosphatase occurred 4 to 11 days after the calpain II
      activity had peaked. Induction of differentiation in long-term MC3T3-E1 cultures
      was associated with higher calpain II and 70- and 110-kDa calpastatin protein
      levels and lower 17-kDa calpastatin degradation product levels. In conclusion,
      cysteine protease activity is essential for preosteoblastic proliferation and
      differentiation. The calpain-calpastatin system is regulated during
      osteoprogenitor proliferation and differentiation, as it is in other cells, and
      bone morphogenetic protein is a specific regulator of calpain II.

PMID- 9194493
TI  - Glutamate-treated rat cortical neuronal cultures die in a way different from the
      classical apoptosis induced by staurosporine.
AB  - The alkaloid protein kinase inhibitor staurosporine induced neuronal cell death
      with both the morphological and the biochemical characteristics of apoptosis. The
      punctate chromatin associated with apoptosis with retention of plasma membrane
      integrity was observed in neurons identified by colocalization of NeuN staining.
      Such cells had DNA fragmentation visualized by in situ end-labeling which was
      seen as a laddered pattern upon gel electrophoresis. In contrast cells treated
      with glutamate did not exhibit either of these morphological or biochemical
      hallmarks of apoptosis. Instead a much smaller and more compact pyknotic
      structure was observed associated with smeared DNA fragmentation patterns. A
      confocal time-lapse study of the appearance of the morphological changes in
      individual nuclei after staurosporine treatment showed collapse into punctate
      chromatin over a period of 10 min. In contrast, the collapse into small pyknotic
      nuclei after glutamate treatment was at least 10 times slower. It is concluded
      that excitotoxicity produced by glutamate did not induce cell death by an
      apoptotic mechanism in cultured cortical neurons.

PMID- 9194494
TI  - Retinoids differentially regulate the proliferation of colon cancer cell lines.
AB  - In this study, the proliferative effects of retinoids were examined in the MC-26
      and LoVo colon adenocarcinoma cell lines. The proliferation of the LoVo cell line
      was not altered in the presence of the retinoids all trans-retinoic acid (atRA)
      and 9-cis-retinoic acid (9-cis-RA). Both retinoids, however, stimulated the
      growth, as measured by cell proliferation, of MC-26 cells. atRA and 9-cis-RA were
      equipotent in increasing MC-26 cell proliferation, suggesting that the growth
      stimulation is mediated by one or more retinoic acid receptors (RARs). To
      determine the RAR which might be responsible for this growth stimulatory effect,
      we characterized the RAR subtypes which were present in both cell lines. mRNA for
      the RAR alpha, RAR beta, and RAR gamma were detected in the MC-26 cell. Of the
      RARs present in MC-26 cells, the RAR alpha does not mediate the growth
      stimulatory effects of retinoids, for a selective RAR alpha antagonist was unable
      to prevent the retinoid-induced increase in MC-26 cell growth. RAR alpha, RAR
      beta, and RAR gamma mRNA are also expressed in the LoVo cell line; the lack of
      growth-stimulation by retinoids in LoVo cells, therefore, does not seem to be due
      to the absence of RARs. The results obtained in these experiments demonstrate
      that the growth response elicited by retinoids can vary between colon cancer
      cells and that the differences in response may not be solely determined by the
      RAR subtypes which are expressed in a colon cancer cell line.

PMID- 9194495
TI  - Laminin-5 inhibits human keratinocyte migration.
AB  - Laminin-5 (previously known as kalinin, epiligrin, and nicein) is an adhesive
      protein localized to the anchoring filaments within the lamina lucida space of
      the basement membrane zone lying between the epidermis and dermis of human skin.
      Anchoring filaments are structures within the lamina lucida and lie immediately
      beneath the hemidesmosomes of the overlying basal keratinocytes apposed to the
      basement membrane zone. Human keratinocytes synthesize and deposit laminin-5.
      Laminin-5 is present at the wound edge during reepithelialization. In this study,
      we demonstrate that laminin-5, a powerful matrix attachment factor for
      keratinocytes, inhibits human keratinocyte migration. We found that the
      inhibitory effect of laminin-5 on keratinocyte motility can be reversed by
      blocking the alpha3 integrin receptor. Laminin-5 inhibits keratinocyte motility
      driven by a collagen matrix in a concentration-dependent fashion. Using antisense
      oligonucleotides to the alpha3 chain of laminin-5 and an antibody that inhibits
      the cell binding function of secreted laminin-5, we demonstrated that the
      endogenous laminin-5 secreted by the keratinocyte also inhibits the
      keratinocyte's own migration on matrix. These findings explain the hypermotility
      that characterizes keratinocytes from patients who have forms of junctional
      epidermolysis bullosa associated with defects in one of the genes encoding for
      laminin-5 chains, resulting in low expression and/or functional inadequacy of
      laminin-5 in these patients. These studies also suggest that during
      reepithelialization of human skin wounds, the secreted laminin-5 stabilizes the
      migrating keratinocyte to establish the new basement membrane zone.

PMID- 9194497
TI  - Opposing effects of activin A and follistatin on developing skeletal muscle
      cells.
AB  - Activin and the activin-binding protein follistatin modulate a variety of
      biological processes and are abundant at sites of muscle development. Activin and
      follistatin were expressed in developing chick pectoral muscle in vivo and in
      primary cell culture. Addition of recombinant activin inhibited muscle
      development in a dose-dependent manner as measured by the number of nuclei in
      myosin heavy chain positive cells and creatine phosphokinase activity.
      Conversely, follistatin potentiated muscle development. The effects of activin
      were found to be distinct from those of the related protein transforming growth
      factor (TGF) beta1. Muscle development was repressed by activin at all time
      points investigated and did not recover with the removal of activin following a
      limited exposure. In contrast, while myogenic differentiation in TGFbeta1 was
      initially repressed, muscle marker expression recovered to control levels--even
      in the continued presence of TGFbeta1. Fibroblast growth factor (FGF) had little
      effect on inhibiton of muscle development caused by activin A. However,
      inhibition of development produced by TGFbeta increased with increasing
      concentrations of FGF. Finally, early expression of myoD and myf5 mRNA by muscle
      cultures in the presence of activin and follistatin was analyzed. Activin-treated
      cultures expressed reduced myoD and myf5 levels at 1.5 days after plating. Myf5
      levels in follistatin-treated cultures were elevated, but, surprisingly, these
      cultures showed a reduction in myoD levels. These data suggest that endogenously
      expressed activin and follistatin are important modulators of muscle development.

PMID- 9194496
TI  - Vascular permeability factor/vascular endothelial growth factor inhibits
      anchorage-disruption-induced apoptosis in microvessel endothelial cells by
      inducing scaffold formation.
AB  - Survival and proliferation of endothelial cells requires both growth factors and
      an appropriate extracellular matrix to which cells can attach. In the absence of
      either, endothelial cells rapidly undergo apoptosis. Thus, when human
      microvascular endothelial cells (HDMEC) are plated on a hydrophobic surface such
      as untreated polystyrene, they rapidly undergo apoptosis and die. The present
      study demonstrates that vascular permeability factor/vascular endothelial growth
      factor (VPF/VEGF), an endothelial cell-selective cytokine, inhibits apoptosis of
      HDMEC cultured on untreated polystyrene and induces these cells to adhere,
      spread, and proliferate. VPF/VEGF-induced HDMEC adhesion was time-dependent,
      required de novo protein synthesis, and was inhibited by a soluble RGD peptide
      but not by an inhibitor of collagen synthesis. Under the conditions of these
      experiments, VPF/VEGF downregulated expression of collagen IV and fibronectin but
      did not change collagen I mRNA levels. VPF/VEGF-induced HDMEC adhesion was
      inhibited by antibodies to alpha(v)beta5 and vitronectin but not by antibodies to
      alpha(v)beta3. Other endothelial growth factors and cytokines such as bFGF, HGF,
      and TGFbeta did not reproduce the VPF/VEGF effect. We suggest that VPF/VEGF
      induces endothelial cells to deposit a scaffolding (likely involving vitronectin)
      that allows them to attach to and proliferate on an otherwise nonsupportive
      surface (hydrophobic polystyrene) and in this manner serves as both a survival
      factor and a growth factor.

PMID- 9194498
TI  - The activation domain of a hormone inducible HTLV-1 Rex protein determines
      colocalization with the nuclear pore.
AB  - Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) Rex is an essential
      regulatory protein that acts at the posttranscriptional level to promote
      expression of unspliced and singly spliced genes of the virus. Rex functions have
      been attributed to at least three separate domains of the protein determining
      nuclear/nucleolar accumulation and RNA binding (overlapping), multimerization,
      and nuclear export of Rex-responsive RNA. The steady-state intracellular
      localization of functional Rex molecules is mainly nucleolar. Fusions of wild
      type Rex and the ligand binding domain of human estrogen receptor (ER) produced
      conditional molecules (ERRex and ERalaRex), which remained cytoplasmic in the
      absence of hormone and in response to hormone colocalized with the nuclear pore
      complex (NPC). These molecules induced in a hormone-dependent manner the
      expression of a Rex reporter plasmid and of the HTLV-1 Env protein and fusion of
      Env expressing cells. In contrast, activation domain mutants (ERRex delta and
      ERRexGly) translocated from the cytoplasm and acquired a diffuse nuclear
      localization. These mutants did not associate with the NPC and failed to show any
      of the expected Rex functions. Rex functions were perturbed by inactivating the
      RNA binding domain (mutant ERM2) or the oligomerization domain (mutant ERM7).
      However, these two mutant fusion proteins exhibited a hormone-dependent NPC
      colocalization. These observations provide in vivo evidence that intranuclear
      translocation of intact Rex to the NPC is dependent exclusively on a functional
      activation domain and is not influenced by binding to the target RNA.

PMID- 9194499
TI  - Apoptosis of terminally differentiated chondrocytes in culture.
AB  - During the process of endochondral ossification chondrocytes progress through
      stages of terminal differentiation culminating in apoptotic death. We have
      developed a serum-free suspension culture that allows terminal differentiation
      and facilitates the investigation of factors affecting chondrocyte apoptosis. We
      have found that chondrocytes not committed to terminal differentiation, i.e.,
      those from the caudal region of chick embryo sterna, a region that remains
      cartilaginous for some months after the chick hatches, maintained high viability
      in serum-free suspension culture. A strong dependence of viability on culture
      density and sensitivity to induction of apoptosis with the protein kinase
      inhibitor, staurosporine, was consistent with the proposal that these
      chondrocytes, like nearly all cells, require intercellular communication for
      survival. Chondrocytes that were committed to terminal differentiation, i.e.,
      those from the cephalic region of chick embryo sterna, a region that is replaced
      by bone before the chick hatches, expressed the hypertrophic phenotype but
      maintained their viability in culture for only approximately 6 days. Subsequent
      cell death was very consistent between cultures and shown to occur by an
      apoptotic process by analysis of DNA fragmentation and cell morphology. Short
      term viability of hypertrophic chondrocytes was independent of culture density
      and relatively resistant to treatment with staurosporine. Induction of the
      hypertrophic phenotype in immature chondrocytes committed them to cell death and
      prevention of expression of the hypertrophic phenotype prevented cell death. We
      conclude that commitment of chondrocytes to terminal differentiation is
      associated with a commitment to apoptosis and apoptosis of hypertrophic
      chondrocytes in growth cartilage does not require initiation by external signals.

PMID- 9194500
TI  - Cytoskeletal and morphological changes associated with the specific suppression
      of the epidermal growth factor receptor tyrosine kinase activity in A431 human
      epidermoid carcinoma.
AB  - The epidermal growth factor (EGF) receptor is well known as a mediator of
      mitogenic signaling and its tyrosine kinase activity has been suggested as a
      viable target in cancer chemotherapy. To explore the consequences of abolishing
      the kinase activity of this receptor, we have utilized a potent and specific
      inhibitor of the enzyme, PD 153035, to sustain a long-term suppression of its
      activity. This compound inhibits EGF receptor autophosphorylation in cells with
      an IC50 in the low nanomolar range and does not block PDGF or FGF receptor kinase
      until concentrations are greater than 10 microM. [1] Human epidermoid carcinoma
      A431 cells were grown in the presence of PD 153035 and were passed weekly until
      cells grew in the presence of 1 microM inhibitor. These cells, referred to as
      A431R, showed a remarkable change in morphology, becoming flattened and spread
      out. A comparison of the sensitivity of EGF receptor autophosphorylation to PD
      153035 between A431 and A431R showed a similar dose response, indicating that the
      cells had not developed any defect in the kinase which might make it resistant to
      the inhibitor. Likewise, EGF receptor autophosphorylation in response to
      exogenously added EGF, as well as receptor internalization, was similar between
      the two cell lines. Furthermore, analysis of A431R cells by flow cytometry showed
      no significant change in DNA content or percentage of cells in any one phase of
      the cell cycle compared to the parent line. 125I-labeled EGF/receptor binding
      studies showed that receptor number in the A431R cells was equivalent to that of
      the parent line; however, the Scatchard plot was linear, in contrast to the
      typical biphasic plot obtained with the parent cells, implying a loss of high
      affinity receptors. Cytoskeletal preparations from both cell lines indicated that
      the A431R had fourfold less EGF receptor associated with the cytoskeleton than
      A431. This was accompanied by a remarkable increase in polymerized actin stress
      fibers throughout the A431R cells, which most likely accounts for their flattened
      morphology. The A431R cells also exhibited a twofold increase in the expression
      of focal adhesion kinase, which is consistent with a greater contact area for
      their cell surface and increase in focal adhesions. Finally, although the A431R
      cells have a doubling time of 24 h, similar to that of the parent line, these
      cells stop growing as the monolayer approaches confluence, reminiscent of the
      contact inhibition seen in nontransformed cells. These data indicate that long
      term suppression of the EGF receptor tyrosine kinase activity in A431 human
      epidermoid carcinoma results in certain cellular properties which are more
      consistent with a differentiated and nontransformed phenotype.

PMID- 9194501
TI  - HSP90alpha gene expression may be a conserved feature of vertebrate
      somitogenesis.
AB  - We have previously demonstrated that the hsp90alpha and hsp90beta genes in
      zebrafish are expressed in dramatically different spatial and temporal patterns
      in early embryos. In the case of hsp90alpha, expression is spatially restricted
      within the somites to putative myogenic cells which also express mRNA encoding
      the myogenic bHLH transcription factor myoD and is downregulated along with myoD
      following myogenesis. In the present study, we have examined hsp90alpha gene
      expression in developing chicken embryos using a gene-specific probe. We show
      that hsp90alpha gene expression is also localized to a subset of cells within the
      somites of chicken embryos and that the expression pattern correlates closely to
      that observed for myoD. Furthermore, expression of the hsp90alpha gene is
      strongly upregulated throughout the embryo following heat shock in a manner
      similar to that observed in heat-shocked zebrafish embryos. The data suggest that
      the hsp90alpha gene may play an evolutionarily conserved role during
      somitogenesis in vertebrates in addition to providing protection to all cells of
      the embryo following stress.

PMID- 9194502
TI  - Phosphorylation of the three Rb protein family members is a common step of the
      cAMP-, the growth factor, and the phorbol ester-mitogenic cascades but is not
      necessary for the hypertrophy induced by insulin.
AB  - Thyrotropin (TSH) through the cAMP cascade and in the presence of insulin induces
      the proliferation of dog thyroid cells. In this work, it is shown that TSH via
      cAMP causes the phosphorylation of the three members of the pRb family, pRb,
      p107, and p130, with the same kinetics as those observed when these cells are
      stimulated by mitogens acting through a tyrosine kinase receptor or through
      activation of kinase C. It is the first described point of convergence of cAMP
      dependent and -independent mitogenic pathways in dog thyrocytes and suggests that
      the phosphorylation of the three proteins may be involved in the initiation of
      DNA synthesis in these cells. We also show that insulin, which induces
      hypertrophy and is permissive for the TSH mitogenic action, does not provoke the
      phosphorylation of any pRb family member, suggesting that none of these
      phosphorylations is required for this effect.

PMID- 9194503
TI  - The relationship of hyperinsulinemic state to left ventricular hypertrophy,
      microalbuminuria, and physical fitness in borderline and mild hypertension.
AB  - The relationship of the hyperinsulinemic state to left ventricular hypertrophy,
      left ventricular geometric patterns, microalbuminuria, and physical fitness were
      studied in 52 middle-aged unmedicated men with borderline and mild hypertension.
      Left ventricular mass index and relative wall thickness were assessed by
      echocardiography. Physical fitness was determined by symptom-limited maximal
      treadmill stress testings. The urinary concentration of microalbumin and C
      peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary
      C-peptide excretion rate was correlated with left ventricular mass index (r =
      0.46), relative wall thickness (r = 0.41), treadmill time (r = -0.35), normalized
      treadmill time (r = -0.52), systolic blood pressure at peak exercise (r = 0.29),
      and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression
      analysis identified the left ventricular mass index, the 24-h urinary albumin
      excretion, and the normalized treadmill time as variables in the equation for the
      24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to
      left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in
      patients with borderline and mild hypertension.

PMID- 9194504
TI  - Effects of cholesterol reduction on BP response to mental stress in patients with
      high cholesterol.
AB  - Impaired endothelium-dependent vascular relaxation has been reported in patients
      with high cholesterol (HC), but the systemic effects of elevated cholesterol on
      blood pressure (BP) and BP reactivity to stress have not been studied. We
      examined the BP response to a standard mental arithmetic test (MAT) in 37
      healthy, normotensive HC subjects and 33 normal cholesterol controls (NC). Both
      groups had similar age, body mass index, and gender distribution. HC had slightly
      higher systolic BP at baseline (122 v 118 mm Hg, P < .05) than NC and systolic BP
      response during MAT was significantly higher in HC compared to NC (18 +/- 8 v 10
      +/- 5 mm Hg, P < .05). Maximal changes in systolic BP were significantly
      correlated with cholesterol (R = 0.41, P < .001), whereas heart rate and
      diastolic BP changes were unrelated to serum cholesterol. To confirm that BP
      reactivity was dependent on cholesterol, MAT was repeated after treatment with 20
      mg/day of lovastatin, a hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA)
      reductase inhibitor, for 6 weeks using a cross-over design in 26 HC subjects.
      Lovastatin significantly altered lipid profiles (-26% total cholesterol, +8% HDL,
      -34% LDL). A small decrease in systolic BP at baseline (-3 mm Hg, P = NS) and
      significantly lower systolic BP (-8 mm Hg, P < .05) during MAT was observed after
      the treatment with lovastatin. In conclusion, patients with high cholesterol had
      an exaggerated systolic BP response to MAT. Decreased BP reactivity during HMG
      CoA reductase inhibitor therapy suggests that lowering cholesterol may have a
      role in the overall control of BP.

PMID- 9194505
TI  - Metabolic effects of long-term treatments with nifedipine-retard and captopril in
      young hypertensive patients.
AB  - The objective of this study was to clarify potential differences in the
      metabolism of glucose and lipids in a long-term treatment (for 5 years) for
      hypertension among nifedipine-retard and captopril in young, nonobese
      hypertensive men (HT). In 78 previously untreated HT who were given nifedipine
      retard and in 81 HT given captopril, blood pressure (BP), pulse rate, blood
      glucose, and plasma insulin levels were measured every 30 min for 2 h after 75 g
      oral glucose ingestion, every year for 5 years. Twenty-six age- and body mass
      index (BMI)-matched normotensive men (NT) were measured for the same variables
      for 5 years. They were also measured for total cholesterol, triglyceride levels,
      and lipids fractions after an overnight fast, every year for 5 years without any
      kinds of lipid lowering agents. At 1 year after treatment with nifedipine-retard
      or captopril, BP decreased significantly, and the reductions in BP did not differ
      between HT treated with nifedipine-retard and captopril. In the entry period,
      fasting insulin (P < .05), the area under the curve (AUC) of insulin (P < .01),
      AUC of blood glucose (P < .05) after 75 g oral glucose ingestion, fasting total
      cholesterol (P < .05), and triglyceride levels (P < .05) in HT were significantly
      greater than those in NT. In HT treated with captopril, AUC of insulin (P < .01),
      AUC of blood glucose (P < .05), and total cholesterol (P < .05) decreased
      significantly after 1 year of treatment for HT, and triglyceride (P < .05)
      decreased significantly after the 2 year treatment. Although in HT treated with
      nifedipine-retard, AUC of insulin (P < .01) and AUC of blood glucose levels (P <
      .05) decreased significantly after 1 year of treatment, triglyceride and total
      cholesterol levels did not decrease throughout the 5 years. These results
      indicate that captopril has ameliorative effects in hyperinsulinemia or reduced
      insulin sensitivity, hypercholesterolemia, and hypertriglyceridemia starting at 1
      year after the treatment for HT, whereas nifedipine-retard has an ameliorative
      effect in the metabolism of glucose but not in the metabolism of lipids.
      Therefore, ACE inhibitor has additional ameliorative effects on insulin
      sensitivity to the vasodilatory action.

PMID- 9194506
TI  - The effects on cardiac arrhythmias of antihypertensive therapy causing regression
      of left ventricular hypertrophy.
AB  - To examine the effects of antihypertensive therapy causing regression of left
      ventricular hypertrophy on cardiac arrhythmias, 26 hypertensive subjects were
      treated with ramipril with felodipine if required, and followed for 6 months
      after blood pressure control. Compared with baseline, left ventricular mass index
      (LVMI) was significantly reduced both at blood pressure control and after a
      further 6 months of treatment (baseline, blood pressure control, 6 months after
      blood pressure control; LVMI 142 +/- 3.6, 131 +/- 3.4, 123 +/- 3.8* g/m2, *P <
      .01 compared with baseline). There was a significant relationship between the
      decrease in systolic blood pressure and the decrease in LVMI after 6 months of
      blood pressure control compared with baseline (r = 0.41, P = .05). Compared with
      baseline, the average total number of ventricular ectopics decreased after blood
      pressure was controlled (88 +/- 59 and 21 +/- 12 respectively); however this
      reduction was not maintained after 6 months of further treatment, either before
      (78 +/- 50) or after drug washout (86 +/- 40). Compared with baseline (639 +/-
      590) supraventricular ectopic total was not initially reduced after blood
      pressure control (650 +/- 604), but was reduced after a further 6 months of
      treatment (294 +/- 261). This reduction was maintained after drug washout (267 +/
      254), although this did not reach statistical significance. Radionuclide
      scanning at baseline was not a predictor of patients with the highest risk of
      arrhythmia and there was no correlation between improvement or worsening of a
      defect with changes in ventricular ectopic total. In conclusion, antihypertensive
      therapy with ramipril and felodipine, although causing regression of left
      ventricular hypertrophy did not lead to a sustained reduction in ventricular
      ectopic total.

PMID- 9194508
TI  - Plasma angiotensinogen concentrations in obese patients.
AB  - A close relationship between obesity and hypertension has been recognized, and
      plasma angiotensinogen concentrations (p-AGT) have been reported to correlate
      with blood pressure (BP). However, little is known about AGT in obese patients
      with hypertension. To define the role of AGT in obese hypertension, we measured p
      AGT in obese patients. The subjects were 42 obese patients diagnosed on the basis
      of a body mass index (BMI) of more than 25 kg/m2, and 21 sex- and age-matched
      nonobese patients, whose BMI was less than 25 kg/m2. The hypertensive patients
      had not previously received antihypertensive drugs. P-AGT (P < .05) and mean BP
      (P < .0001) was increased in the obese patients as compared with the nonobese
      patients. Positive correlations were observed between BMI and p-AGT, mean BP and
      p-AGT, and BMI and mean BP (all P < .05). However, after adjustment for blood
      pressure, p-AGT was not different between groups, and after adjustment a positive
      correlation remained only between BMI and mean BP. These results suggested the
      possible involvement of increased p-AGT in hypertension in obese patients,
      although this may be a secondary change to hypertension or obesity.

PMID- 9194507
TI  - Relations of Doppler stroke volume and its components to left ventricular stroke
      volume in normotensive and hypertensive American Indians: the Strong Heart Study.
AB  - Doppler echocardiographic measurement of time-velocity integral of blood flow
      across the aortic annulus ("stroke distance") or of stroke volume (SV) have been
      proposed as noninvasive measures of cardiac pump performance that could elucidate
      the hemodynamics of hypertension. To evaluate the performance of these measures
      of hemodynamic volume load in a population with a wide range of body build and
      other characteristics, we obtained technically adequate imaging and Doppler
      echocardiograms in 1,935 of 2,212 (87%) American Indian Strong Heart Study
      participants, without mitral regurgitation or segmental left ventricular (LV)
      dysfunction, in Arizona, Oklahoma, and South/North Dakota. The subjects ranged
      widely in age (48 to 81 years) and body mass index (17.0 to 62.6 kg/m2); 65% were
      women; 1,161 were normotensive and 774 were hypertensive. As a reference
      standard, LV and stroke volumes were calculated from LV internal dimensions by
      the Teichholz method. Doppler SVs were moderately related to LV SVs (r = 0.63),
      but Doppler SV was slightly lower in both normotensive (mean = 69.8 and 72.9 mL,
      respectively) and hypertensive subjects (71.1 v 73.6 mL). Aortic stroke distance
      was less closely related than was aortic annular area to LV SV (r = 0.34 v 0.40,
      P < .001). Aortic annular area (r = 0.44) but not stroke distance (r = 0.04) was
      moderately correlated with body surface area. Stroke distance was inversely
      related to annular area (r = -0.29) and in subjects stratified by aortic annular
      diameter 1.6 to 1.9, 2.0 to 2.1, and 2.3 to 2.9 cm, mean LV SV increased from 67
      to 74 to 80 mL, but average stroke distance fell from 22.8 to 21.6 to 20.1 cm.
      Stroke distance also failed to identify gender differences in LV SV but did
      identify that due to obesity. Thus Doppler SV closely parallels independently
      measured LV SV but slightly underestimates SV in both normotensive and
      hypertensive adults, whereas aortic stroke distance yields misleading comparisons
      between genders or individuals of different body sizes.

PMID- 9194509
TI  - Is diastolic hypertension an independent risk factor for stroke in the presence
      of normal systolic blood pressure in the middle-aged and elderly?
AB  - In a prospective population-based study from the Copenhagen City Heart Study, the
      role of diastolic blood pressure as an independent risk factor of stroke, in the
      presence of normal systolic blood pressure, was assessed in 6,545 subjects aged
      50 to 80 years. Follow-up was 12 years. Subjects were divided into various blood
      pressure categories according to both diastolic and systolic blood pressure. The
      risk of stroke was assessed using a multivariate Cox proportional hazards model,
      taking into account various cardiovascular risk factors (age, sex, smoking,
      diabetes mellitus, body mass index, and levels of serum cholesterol). After
      adjustment for risk factors, only subjects with elevated systolic blood pressure
      had a significantly increased risk of future stroke. The risk of stroke according
      to blood pressure categories further reflected increasing levels of pulse
      pressure, with the highest risk of stroke in subjects with the greatest pulse
      pressure. We conclude that systolic blood pressure is a better predictor of
      stroke than is diastolic blood pressure, and question whether diastolic blood
      pressure, in the presence of normal systolic blood pressure, is an independent
      risk factor for stroke in the middle-aged and elderly.

PMID- 9194510
TI  - Short-term antihypertensive medication does not exacerbate sleep-disordered
      breathing in newly diagnosed hypertensive patients.
AB  - It has been speculated for some time that various antihypertensive medications
      may have a deleterious effect on respiration during sleep and thereby enhance the
      apparent association between hypertension and sleep apnea/hypopnea (SAH).
      However, there are few data to support this contention. The present study used a
      double-blind, randomized, cross-over design to contrast the effects of 6 weeks
      treatment with alpha-methyldopa and the combination of hydrochlorothiazide and
      amiloride with that of amlodipine and the combined diuretics in a group of 24
      newly diagnosed patients with primary hypertension. All-night polysomnography was
      performed before the initiation of therapy (baseline) and at the end of the two
      treatment periods. Respiratory variables failed to reveal any significant
      differences between the treatments and baseline, or between the two different
      treatment regimens. The two treatment regimens achieved similar reductions in
      blood pressure. The prevalence of SAH was 25% before treatment, which is
      comparable to a prevalence of 20% in a similar group drawn from the same
      population but receiving various antihypertensive medications. The findings of
      this study are in agreement with previous reports using other classes of
      antihypertensive drugs that also failed to detect any tendency for increases in
      nocturnal respiratory disturbance indices over assessment periods of 8 weeks or
      shorter.

PMID- 9194511
TI  - Hyperinsulinemia induces myocardial infarctions and arteriolar medial hypertrophy
      in spontaneously hypertensive rats.
AB  - To investigate the effects of hyperinsulinemia on the myocardial vessels, long
      acting insulin (mixtard, a combination of 30% regular human insulin and 70% NPH
      human insulin) was injected daily for 8 weeks, intraperitoneally, in two strains
      of rats, normotensive WKY and hypertensive SHR. There were four groups in all, a
      control group, and an insulin-injected group in each strain. The drinking water
      contained 10% glucose to prevent hypoglycemia in the insulin-injected rats. At
      the end of the 8 weeks experimental period, after measuring blood pressure and
      taking blood for the determination of glucose, urea, creatinine, and insulin, the
      rats were killed. The organs were fixed in formaldehyde. The blood glucose levels
      were higher at the end of the experiment, in both the placebo- (saline)-injected
      and the insulin-injected rats. Blood pressure rose significantly only in the
      insulin-injected SHR. The intramyocardial arterioles in the insulin-injected SHR
      had a significantly thicker vascular wall than the placebo-injected SHR, as
      represented by the vessel wall to lumen ratio, because of hypertrophy of the
      media. When compared with the placebo injected WKY rats, there was a higher
      wall/lumen ratio of the intramyocardial arterioles in the insulin-injected WKY,
      but the difference did not reach significance. Heart weights factored by body
      weights was significantly higher in insulin-injected as compared with placebo
      injected SHR. Myocardial infarctions were observed in four of eight rats in the
      insulin-injected SHR group despite the fact that there were no signs of
      atherosclerosis or intimal thickening. It is possible that the increase in heart
      weight and the probable increase in metabolic activity resulting from
      hyperinsulinemia, together with the increased oxygen demand of the myocardium and
      the arteriolar narrowing, may have contributed to the occurence of myocardial
      infarctions in the absence of atherosclerotic coronary occlusion.

PMID- 9194512
TI  - Human brain natriuretic peptide reduces blood pressure in normotensive and acute
      norepinephrine-induced hypertensive rabbits.
AB  - Human brain natriuretic peptide (hBNP) is a cardiac-derived peptide hormone with
      potent hemodynamic and renal effects in dogs, monkeys, and humans, but not in
      rats. At present there is no small animal model to study the actions of hBNP.
      These studies describe the effects of hBNP in New Zealand White rabbits in
      normotensive and acute norepinephrine-induced hypertensive states. Intravenous
      administration of hBNP (1, 3, 10, and 30 microg/kg) to anesthetized rabbits
      resulted in a dose-dependent diuresis and natriuresis and a decrease in systolic
      blood pressure. Bolus administration of hBNP resulted in a time- and dose
      dependent accumulation of plasma cyclic GMP, consistent with activation of a
      particulate guanylyl cyclase receptor. The hemodynamic actions of hBNP suggest
      clinical utility for the management of acute hypertension associated with
      numerous surgical procedures, a condition linked to catecholamine activation. In
      rabbits with norepinephrine-induced acute hypertension, bolus and continuous
      infusion of hBNP markedly reduced blood pressure. These studies demonstrate that
      the rabbit is a useful species to study the hemodynamic and renal effects of hBNP
      and that this peptide may have therapeutic utility for the acute reduction of
      hypertension associated with catecholamine activation.

PMID- 9194513
TI  - Chronic estrogen treatment in female transgenic (mRen2)27 hypertensive rats
      augments endothelium-derived nitric oxide release.
AB  - Postmenopausal estrogen replacement therapy is associated with a reduction in
      cardiovascular events in women, but the mechanisms for this protection are
      unclear, especially in hypertensive subjects. In this study we investigated the
      effects of 17beta-estradiol (E2) treatment on blood pressure and endothelial
      function of transgenic [(mRen2)27] hypertensive and normotensive rats. Thirty
      female transgenic negative [Tg(-)] and hypertensive positive [Tg(+)] rats were
      ovariectomized and received either E2 (1.5 mg/rat, subcutaneously, for 3 weeks)
      or placebo. Chronic 17beta-estradiol treatment lowered mean blood pressure in
      both Tg hypertensive (159 +/- 4 v 145 +/- 4 mm Hg, P < .05, placebo v E2) and
      normotensive rats (119 +/- 4 v 108 +/- 2 mm Hg, P < .05, placebo v E2). Pressor
      responses to intravenous injection of phenylephrine were augmented in the Tg(+)
      as compared with Tg(-) rats. With chronic E2 treatment the pressor responses to
      phenylephrine were attenuated in both groups. Isometric tension of aortic rings
      was measured in vitro in organ chambers. The acetylcholine (Ach)-induced
      endothelium-dependent vascular relaxation was less potent in Tg(+) versus Tg(-)
      rats. E2 treatment significantly enhanced the Ach-induced relaxation of both
      Tg(+) and Tg(-) groups (ED50: 55.5 +/- 11.7 v 10.3 +/- 2.6; 23.8 +/- 6.5 v 5.1 +/
      1.2 nmol/L, placebo v E2 in Tg(+) and Tg(-), respectively). After E2 treatment
      the ED50 response in Tg(+) rats was no different from Tg(-) rats. However, the
      maximum vasodilation elicited by Ach was attenuated in Tg(+) as compared with Tg(
      ) rats. The calcium ionophore (A23187)-induced endothelium-dependent relaxation
      was less potent in Tg(+) as compared to Tg(-) rats and was enhanced by E2
      treatment only in Tg(+) animals. There were no differences in the vasodilator
      responses elicited by sodium nitroprusside. Removal of endothelium and blockade
      of NO production abolished the endothelium-dependent vasodilation. The selective
      NO synthase inhibitor, N(G)-monomethyl-L-arginine (LMMNA), was used to evaluate
      indirectly the basal contribution of NO in vascular rings. The response to LMMNA
      was attenuated in untreated Tg(+) as compared to Tg(-) rats. E2 treatment
      augmented the contraction response to NOS inhibition in both Tg(+) and Tg(-)
      rats, resulting in a response in Tg(+) rats that was no different from Tg(-)
      rats. These results indicate that untreated, surgically ovariectomized
      hypertensive rats show deficiencies in endothelial function, which can be
      improved by estrogen replacement.

PMID- 9194514
TI  - Effects of SC-52458, an angiotensin AT1 receptor antagonist, in the dog.
AB  - We have previously reported on the basic 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 angiotensin (AII) receptor antagonist that binds
      potently to AT1 receptors in rat adrenal cortex and blocks AII-mediated
      contraction in isolated rabbit aorta. In the present study, the ability of SC
      52458 to block AII pressor responses in conscious dogs was measured. In addition,
      we determined whether SC-52458 lowered mean arterial pressure in dogs with 2
      kidney/1 clip renal hypertension when given daily for 4 days. In conscious,
      normotensive dogs, SC-52458 at 30 mg/kg orally, blocked the pressor response to
      AII (50 ng/kg, intravenously) with maximal inhibition (91%) observed 2 h after
      dosing. Plasma concentrations of SC-52458 measured by HPLC also were highest at
      the 2-h time point. After 24 h, the AII pressor response remained inhibited (by
      35%) and SC-52458 was still measurable in plasma from treated dogs. In dogs made
      hypertensive by constriction of the left renal artery, SC-52458 lowered mean
      arterial pressure compared to vehicle treatment although heart rate was not
      different in the two groups. The maximal blood pressure lowering achieved with SC
      52458 was similar to the maximal effect observed with the angiotensin converting
      enzyme inhibitor lisinopril. We conclude that SC-52458 blocks AII mediated
      pressor responses in normotensive, conscious dogs and SC-52458 is an efficacious
      antihypertensive agent in dogs with 2 kidney/1 clip renal hypertension.

PMID- 9194515
TI  - Hypertension and abnormalities of carbohydrate metabolism possible role of the
      sympathetic nervous system.
AB  - To investigate the relationships between the sympathetic nervous system (SNS) and
      parameters of glucose metabolism in arterial hypertension, daily urinary
      excretion of catecholamines and plasma glucose, insulin, and C-peptide response
      to an oral glucose load (OGL) have been evaluated in 77 untreated patients with
      mild-to-moderate essential hypertension and in 31 normotensive controls. Urinary
      excretion of norepinephrine (UNE) was positively correlated with body mass index
      and with plasma glucose levels both at fast and after OGL. No correlations were
      found between urinary excretion of catecholamines and plasma insulin and C
      peptide levels both at fast and in response to OGL. Because the frequency
      distribution of UNE was bimodal, hypertensive subjects were separated into two
      subgroups using an arbitrary cutoff, and the parameters of glucose metabolism
      were compared. Subjects with UNE > 205 microg/day had greater levels of fasting
      glucose and greater glycemic response to OGL than subjects with UNE < 205
      microg/day, whereas no significant differences between the groups were found in
      fasting and stimulated plasma insulin and C-peptide. Thus, activation of SNS is
      related to glucose tolerance but not hyperinsulinemia and insulin hypersecretion
      in essential hypertension. Plasma glucose levels, independent of insulin, may
      contribute to the relationship between SNS activity and blood pressure in
      essential hypertension.

PMID- 9194516
TI  - Effect of acute N-nitro-L-arginine methyl ester (L-NAME) hypertension on glucose
      tolerance, insulin levels, and [3H]-deoxyglucose muscle uptake.
AB  - This study was conducted to test the hypothesis that acute, widespread N-nitro-L
      arginine methyl ester (L-NAME) induced vasoconstriction and hypertension may
      affect glucose tolerance and insulin sensitivity in normal rats. Comparisons were
      made of blood pressure, intravenous glucose tolerance, and insulin response and
      [3H]-deoxyglucose tissue uptake between L-NAME and control treated rats.
      Chronically instrumented, awake rats were administered L-NAME (30 mg/kg) (n = 8)
      or saline (0.3 mL) (n = 8) intravenously. After blood pressure stabilized, a
      bolus injection containing glucose (300 mg/kg) and trace [3H]-deoxyglucose was
      administered. Arterial blood was sampled for evaluation of glucose tolerance,
      insulin response, and [3H]-deoxyglucose muscle uptake. L-NAME treated rats had a
      persistent 54 +/- 4 mm Hg blood pressure rise while fasting, and postload plasma
      glucose and insulin responses did not differ, nor did heart and striated muscle
      [3H]-deoxyglucose uptake differ. In conclusion, acute L-NAME induced hypertension
      does not result in glucose intolerance, hyperinsulinemia, or decreased [3H]
      deoxyglucose muscle uptake.

PMID- 9194517
TI  - Ambulatory blood pressure monitoring for detecting the relation between
      angiotensinogen gene polymorphism and hypertension.
AB  - Compared to office measurements, ambulatory monitoring is a more accurate method
      of blood pressure (BP) characterization and may therefore be useful in a genetics
      study of hypertension. We studied the relation between the M235T polymorphism of
      the angiotensinogen gene and hypertension using office and ambulatory (BP)
      measurements. We enrolled untreated subjects (33 men and 17 women) who were
      referred for evaluation of office BP >140/90 mm Hg on at least two separate
      occasions. The M235T genotypes of the angiotensinogen gene were determined by
      polymerase chain reaction (PCR) amplification of DNA extracted from peripheral
      blood leukocytes and digested with BSTU1. The distribution of the genotypes were
      MM = 0.22, MT = 0.44, TT = 0.34. Based on office measurements, a significant
      difference in diastolic blood pressure (BP) was detected only between the TT and
      the MT genotype subjects (office BP: MM = 150 +/- 25/97 +/- 13 mm Hg, MT = 147 +/
      23/ 95 +/- 13 mm Hg, TT = 161 +/- 25/104 +/- 15 mm Hg). By contrast, with
      ambulatory BP monitoring, both systolic and diastolic blood pressures were
      significant higher in TT versus MM and MT (ambulatory BP, MM = 138 +/- 10/88 +/-
      9 mm Hg, MT = 141 +/- 15/89 +/- 11 mm Hg, TT = 152 +/- 18/97 +/- 12 mm Hg).
      Covariate analysis revealed an independent relationship between the M235T
      genotype and systolic, diastolic, and mean ambulatory BP. Ambulatory monitoring
      improved the analytic power of our study and allowed detection of a clear and
      consistent relationship between angiotensinogen polymorphism and hypertension
      with a relatively small sample size.

PMID- 9194518
TI  - No effect of genetic variation at the angiotensinogen locus on ambulatory blood
      pressure level in normotensive subjects.
AB  - The aim of the study was to evaluate the potential association between ambulatory
      blood pressure and the molecular variants T174M and M235T of the angiotensinogen
      gene in a random sample of young normotensive men (n = 145). The two point
      mutations were detected using restriction digests of a mispairing polymerase
      chain reaction product. Twenty-four-hour ambulatory blood pressure monitoring was
      performed with a SpaceLabs 90207 device. Ambulatory blood pressure levels did not
      vary according to T174M and M235T genotypes. When the subjects were grouped
      according to their blood pressure level (as indicated by tertiles of their 24-h
      ambulatory blood pressure), no significant differences in allele frequencies
      between the three groups were found. Our results indicate that the T174M and
      M235T molecular variants of the angiotensinogen gene have no major influence on
      ambulatory blood pressure in young normotensive subjects.

PMID- 9194520
TI  - Continuing innovations for health.

PMID- 9194521
TI  - Sulfation and sulfotransferases 5: the importance of 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) in the regulation of sulfation.
AB  - Sulfation is the transfer of a sulfate group from 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) to a substrate that is catalyzed by a family of
      sulfotransferase enzymes. Many different endogenous and xenobiotic molecules are
      substrates for the sulfotransferases; sulfation affects many different
      physiological processes, including: 1) deactivation and bioactivation of
      xenobiotics, 2) inactivation of hormones and catecholamines, 3) structure and
      function of macromolecules, and 4) elimination of end products of catabolism.
      PAPS is the obligate cosubstrate that is synthesized in tissues to make available
      an "activated form" of sulfate for the sulfation reaction. PAPS participation in
      the reaction is dependent on its availability, which in turn is dependent on its
      synthesis, degradation, and ultimately its utilization in the sulfation reaction
      itself. PAPS synthesis is dependent on the availability of sulfate and on the
      activity of the two enzymes of its synthesis, ATP-sulfurylase and APS-kinase.
      Although the kinetic properties of these two enzymes are well described, their in
      vivo regulation is not fully understood. Sulfation is a high-affinity, low
      capacity enzymatic process in which the entire liver content of PAPS can be
      consumed in less than 2 min. ATP-sulfurylase and APS-kinase can rapidly
      synthesize additional PAPS. The low capacity of sulfation in rats is due to the
      limited availability of sulfate, whereas in mice the sulfotransferases appear to
      limit sulfation capacity. Sulfation rates are not readily enhanced, but they can
      be decreased. 2,6-Dichloro-4-nitrophenol inhibits phenolsulfotransferases, but
      not hydroxysteroid-sulfotransferases. However, the sulfation of phenols and
      hydroxysteroids can be decreased by factors that decrease sulfate availability
      such as a low-sulfate diet, other xenobiotics that are sulfated, and molybdate,
      which inhibits sulfate intestinal absorption, renal reabsorption, and sulfate
      incorporation into PAPS.

PMID- 9194522
TI  - Cytochromes P450 12: diversity of ACTH (cAMP)-dependent transcription of bovine
      steroid hydroxylase genes.
AB  - An essential role of ACTH is to assure that optimal steroidogenic capacity is
      maintained in the adrenal cortex throughout life. This is achieved by maintaining
      transcriptional pressure on the genes encoding the adrenocortical steroid
      hydroxylases via the second messenger, cAMP. Even though these genes respond
      coordinately to cAMP, it has been surprising to discover that each gene uses its
      own unique cAMP response system during this coordinate response. Thus, different
      cis elements and sets of transcription factors control the cAMP responsiveness of
      each different steroid hydroxylase gene. Although the physiological basis of this
      diversity in biochemical mechanisms of transcriptional regulation is not
      apparent, a portion of this signaling pathway is common to all of these genes. In
      particular, the action of cAMP-dependent protein kinase and an as yet
      uncharacterized cycloheximide-sensitive step are necessary for ACTH-mediated
      transcription of each gene. Biochemical characterization of these common steps in
      the ACTH-dependent signaling pathways is essential to an understanding of the
      maintenance of optimal steroidogenic capacity in the adrenal cortex.

PMID- 9194523
TI  - The tetraspanin superfamily: molecular facilitators.
AB  - A legacy of molecular evolution is the formation of gene families encoding
      proteins that often serve related functions. One such family gaining recent
      attention is the tetraspanin superfamily, whose membership has grown to nearly 20
      known genes since its discovery in 1990. All encode cell-surface proteins that
      span the membrane four times, forming two extracellular loops. Some of these
      genes are found in organisms as primitive as schistosomes and nematodes.
      Alternately known as the transmembrane 4 (TM4) superfamily or the TM4SF, 4TM, or
      tetraspan family, we propose here that the name tetraspanins be used for the
      purpose of standardization. What do the tetraspanins do? Awaiting definitive
      functional studies, we can only put together pieces of a puzzle that has been
      built by raising antibodies against these proteins and looking at their
      distribution, associations, and functions. A brief overview indicates that some
      tetraspanins are found in virtually all tissues (CD81, CD82, CD9, CD63), whereas
      others are highly restricted, such as CD37 (B cells) or CD53 (lymphoid and
      myeloid cells). Many of these proteins have a flair for promiscuous associations
      with other molecules, including lineage-specific proteins, integrins, and other
      tetraspanins. In terms of function, they are involved in diverse processes such
      as cell activation and proliferation, adhesion and motility, differentiation, and
      cancer. We propose that these functions may all relate to their ability to act as
      "molecular facilitators," grouping specific cell-surface proteins and thus
      increasing the formation and stability of functional signaling complexes.

PMID- 9194524
TI  - Interactive effects of nitric oxide and the p53 tumor suppressor gene in
      carcinogenesis and tumor progression.
AB  - The tumor suppressor gene product p53 plays an important role in the cellular
      response to DNA damage. DNA damage can lead to p53-mediated growth arrest and
      apoptosis. High concentrations of nitric oxide (NO) and NO metabolites such as
      peroxynitrite and NO2 cause DNA damage and have been shown to be mutagenic.
      Furthermore, NO induces p53 accumulation and, as part of a feedback loop, p53
      mediates transcriptional transrepression of inducible nitric oxide synthase.
      Recent studies have shown increased expression and activity of nitric oxide
      synthase isoforms in human cancer. NO has both genotoxic and angiogenic
      properties, so that increased NO production may select mutant p53 cells and
      contribute to human carcinogenesis and tumor progression.

PMID- 9194525
TI  - Different roles of D-amino acids in immune phenomena.
AB  - Peptides and polypeptides either fully or partially built of D-amino acids
      interest researchers because of their advantages over all L peptides and
      polypeptides. In exploiting these characteristics, one should realize that the
      resulting molecules are nonetheless not inert, but rather may induce a unique
      immune response, which is hardly cross-reactive with the L-enantiomer. Moreover,
      cross-reaction between the L- and the D-sequences is limited also at the T cell
      level, probably due to different sterical conformations of the MHC-antigen-T cell
      receptor complexes formed. Polypeptides built exclusively of D-amino acids lead
      to antibody formation only at a relatively low concentration, otherwise they
      provoke immunological paralysis. The specificity of the immune response toward
      peptides containing D-amino acid residues is exquisite, and often D-amino acids
      play a dominant role in defining the specificity. Polypeptides composed
      exclusively of D-amino acids are thymus-independent antigens. Nevertheless, it is
      possible to prepare against them highly specific T cell hybridomas. In future
      plans for synthetic vaccines against infectious or autoimmune diseases, the
      inclusion of D-amino acids may be an advantage in terms of both specificity and
      efficacy, the latter because of longer persistence in an undigested form because
      they resist enzymatic degradation.

PMID- 9194526
TI  - The codependence of angiogenesis and chronic inflammation.
AB  - Angiogenesis is the growth of new blood vessels from existing ones. It is an
      important aspect of new tissue development, growth, and tissue repair. It is also
      a component of many diseases including cancer, blindness, and chronic
      inflammation such as rheumatoid arthritis (RA) and psoriasis. There is
      considerable evidence to suggest that angiogenesis and chronic inflammation are
      codependent; recent studies have begun to reveal the nature of this link, which
      involves both augmentation of cellular infiltration and proliferation and
      overlapping roles of regulatory growth factors and cytokines. Through these
      studies, we have begun to understand the codependence of chronic inflammation and
      angiogenesis, the potential benefits of targeting angiogenesis in the treatment
      of chronic inflammation, and of targeting chronic inflammation to affect
      angiogenesis.

PMID- 9194527
TI  - Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes
      from rat thymus and spleen.
AB  - In the present work we analyze by reverse transcription, polymerase chain
      reaction, cDNA cloning, and sequence analysis the expression of membrane
      melatonin receptors in rat thymus and spleen. Results show, for the first time,
      that the melatonin receptor mRNA is expressed in both the thymus and spleen.
      Moreover, the melatonin receptor mRNA was expressed in all the lymphocyte
      subpopulations (CD4+,CD8+, double positive, double negative, and B cells) studied
      from the rat thymus. The Southern blot analysis with the melatonin receptor probe
      and sequence data also showed the identity of the DNA fragments in thymus,
      spleen, and the lymphocyte subpopulations studied. The melatonin receptor
      fragments amplified from rat brain, thymus, and spleen share identical nucleotide
      sequences with the rat Mel1a-melatonin receptor subtype. No signal was obtained
      with primers used to amplify the rat Mel1b-melatonin receptor subtype in both
      thymus and spleen. Finally, the melatonin receptor mRNA transcript distribution
      throughout the rat thymus was examined. Using digoxigenin-labeled cRNA probe to
      the specific melatonin receptor mRNA, examination of the whole thymus revealed a
      clear hybridization signal in both cortex and medulla. Melatonin receptor gene
      expression in the thymus and spleen supports the notion of the immunomodulatory
      role of melatonin.

PMID- 9194528
TI  - Thymosin beta 4 stimulates directional migration of human umbilical vein
      endothelial cells.
AB  - Thymosin beta 4 (T beta 4) is a 4.9 kDa polypeptide that interacts with G-actin
      and is thought to be an important mediator in cell proliferation, migration, and
      differentiation. T beta 4 has been identified as a factor involved in the
      differentiation of human umbilical vein endothelial cells (HUVECs) cultured on
      Matrigel. Here we have used various in vitro and in vivo migration assays to
      demonstrate the role of T beta 4 in endothelial cell migration. Our results
      demonstrate that T beta 4 acts as a chemoattractant for endothelial cells,
      stimulating the migration of HUVECs in Boyden chambers four- to sixfold over that
      observed with media alone. Of the primary cell types tested, only human coronary
      artery cells responded to T beta 4 treatment, suggesting that the migration
      activity of T beta 4 was endothelial cell-specific. T beta 4 significantly
      accelerated the rate of migration into the scratch wounded area of a HUVEC
      monolayer. T beta 4 treatment also increased the production of matrix
      metalloproteinases that may degrade the basement membrane during angiogenesis.
      Additional experiments using subcutaneously implanted Matrigel showed that T beta
      4 stimulated cell migration in vivo. These results provide the first direct
      evidence that T beta 4 has chemoattractive activity and promotes angiogenesis by
      stimulating the migration of endothelial cells.

PMID- 9194529
TI  - Decrease of heart protein kinase C and cyclin-dependent kinase precedes death in
      perinatal asphyxia of the rat.
AB  - Acidosis, energy depletion, overstimulation by excitatory amino acids, and free
      radical-mediated reactions are the major current concepts for the explanation of
      damage and death resulting from asphyxia. Impaired phosphorylation by protein
      kinase C (PKC) represents another mechanism incriminated for cell death. We used
      an unsophisticated perinatal asphyxia model to study heart protein kinases PKC
      and cyclin dependent kinase (CDK). Tissue pH, ATP, the antioxidant enzymes
      superoxide dismutase, catalase, and glutathion peroxidase, lipid peroxidation
      products, carbonyls, and aromatic hydroxylation were also tested. Electron spin
      resonance was applied to demonstrate the possible presence of radical adducts. An
      ELISA method was used to determine cell death. PKC activity and mRNA decreased
      with the length of the asphyctic periods and were paralleled by CDK and pH,
      whereas cell death gradually increased. No evidence was found for the involvement
      of active oxygen species or a radical adduct, and no energy depletion was
      observed. We conclude that impaired protein phosphorylation and/or acidosis may
      play a role in the pathobiochemistry of death from perinatal asphyxia in the rat.

PMID- 9194530
TI  - Vibrational force alters mRNA expression in osteoblasts.
AB  - Serum-deprived mouse osteoblastic (MC3T3E1) cells were subjected to a vibrational
      force modeled by NASA to simulate a space shuttle launch (7.83 G rms). The mRNA
      levels for eight genes were investigated to determine the effect of vibrational
      force on mRNA expression. The mRNA levels of two growth-related protooncogenes, c
      fos and c-myc, were up-regulated significantly within 30 min after vibration,
      whereas those of osteocalcin as well as transforming growth factor-beta1 were
      decreased significantly within 3 h after vibration. No changes were detected in
      the levels of beta-actin, histone H4, or cytoplasmic phospholipase A2 after
      vibration. No basal levels of cyclooxygenase-2 expression were detected. In
      addition, the extracellular concentrations of prostaglandin E2 (PGE2), a potent
      autocrine/paracrine growth factor in bone, were not significantly altered after
      vibration most likely due to the serum deprivation state of the osteoblasts. In
      comparison with the gravitational launch profile, vibrational-induced changes in
      gene expression were greater both in magnitude and number of genes activated.
      Taken together, these data suggest that the changes in mRNA expression are due to
      a direct mechanical effect of the vibrational force on the osteoblast cells and
      not to changes in the local PGE2 concentrations. The finding that launch forces
      induce gene expression is of utmost importance since many of the biological
      experiments do not dampen vibrational loads on experimental samples. This lack of
      dampening of vibrational forces may partially explain why 1-G onboard controls
      sometimes do not reflect 1-G ground controls. These data may also suggest that
      scientists use extra ground controls that are exposed to launch forces, have
      these forces dampened on launched samples, or use facilities such as Biorack that
      provide an onboard 1-G centrufuge in order to control for space shuttle launch
      forces.

PMID- 9194531
TI  - A novel regulatory function of proteolytically cleaved VEGF-2 for vascular
      endothelial and smooth muscle cells.
AB  - By high throughput sequencing, we have identified a cDNA encoding a polypeptide
      related to vascular endothelial growth factor (VEGF) and placenta growth factor
      (PlGF) in the VEGF/PDGF gene family. It is designated vascular endothelial growth
      factor 2 (VEGF-2). Similar to VEGF, expression of VEGF-2 mRNA is abundant in
      vascular smooth muscle cells and several highly vascularized tissues. VEGF-2
      protein is expressed as a secreted 52 kDa precursor as well as the 30 kDa amino
      terminal and 27 kDa carboxy-terminal cleavage products. The latter two cleavage
      products are linked via a disulfide bridge (or bridges) and can be copurified.
      Using copurified 30 and 27 kDa proteins, the effect of VEGF-2 on growth of
      several cell types, including vascular endothelial and smooth muscle cells, was
      determined. Our results demonstrate that VEGF-2 protein stimulates the growth of
      human vascular endothelial cells but inhibits growth of human aortic smooth
      muscle cells induced by platelet-derived growth factor. These studies establish
      VEGF-2 as a novel regulator for growth of vascular endothelial and smooth muscle
      cells.

PMID- 9194532
TI  - Experimental model of short-time exercise-induced preconditioning in POAD
      patients.
AB  - Regular physical exercise improves walking performance in patients affected with
      peripheral obliterative arterial disease (POAD). The mechanisms underlying the
      phenomenon are still controversial. In order to verify the hypothesis that
      physical conditioning of lower limbs on a treadmill and ischemic preconditioning
      of the heart could share some biological aspects, 14 POAD subjects underwent a
      training program on the treadmill consisting of five repeated submaximal
      exercises at five-minute and two-hour intervals preceding the maximal tolerance
      test. Moreover, a protocol with two daily submaximal walking exercises over one
      week was also performed. Pain-free and total walking distance were measured
      before and after they performed the program. Moreover, plasma levels of adenosine
      and adenosine triphosphate (ATP) were measured and polymorphonuclear (PMN)
      leukocyte activity was studied together with rheologic parameters. Pain-free
      distance was prolonged by 15.4% and 14.3%, and total distance was prolonged by
      23.1% and 26.9%, in the exercises with five-minute and two-hour intervals,
      respectively. After one week of daily exercises, the onset of pain and the end of
      the test were delayed by 24% and 43.7%, respectively. An improvement in blood
      rheology and a reduced PMN reactivity were also observed with the three
      protocols, associated with an increase in plasma levels of adenosine and ATP.
      Similarly to ischemic preconditioning in the heart, the possibility is suggested
      that an adenosine-mediated mechanism may contribute to the development of
      physical conditioning in treadmill-trained POAD patients.

PMID- 9194533
TI  - Acute rheumatic fever in an Arabian Gulf country--effect of climate, advantageous
      socioeconomic conditions, and access to medical care.
AB  - An eleven-year study of the incidence and consequences of acute rheumatic fever
      was carried out in a country in which a uniform climate together with national
      characteristics of insularity, wealth, and unrestricted access to free medical
      care contribute prominently to the epidemiologic milieu. Study subjects were 86
      children, aged four to fourteen years, satisfying criteria for acute rheumatic
      fever. Study methods included clinical evaluation, standard laboratory studies,
      and echocardiography. A declining incidence of rheumatic episodes, ranging from
      1.06 to 18.6/100,000 population (average 11.2/100,000), was identified. The
      course of the episode was generally mild. Arthritic findings predominated (92%),
      followed by carditis identified clinically in 43% and, with the addition of
      echocardiography, in 71%. Residual valvular regurgitation, as a longer term
      consequence, persisted in 46% of those with auscultatory confirmation of
      valvulitis. No recurrences were identified. Comparison with countries of similar
      socioeconomic status revealed relatively unimportant differences. Comparison with
      nearby disadvantaged countries identified striking contrast. It may be concluded
      that among the contributing factors, for the improvement in the incidence and
      sequelae of a rheumatic episode, are an advantaged socioeconomic environment and
      accessibility to unlimited medical care.

PMID- 9194535
TI  - Predictive value of left ventricular response to exercise in patients with
      dilated cardiomyopathy--assessment by radionuclide ventriculography.
AB  - The objective of this study was to determine noninvasively the likelihood of
      recovery of the left ventricular ejection fraction (LVEF) in patients with
      dilated cardiomyopathy (DCM) verified by radionuclide ventriculography. Twenty
      patients with DCM were classified into two groups according to the LVEF by M-mode
      echocardiographic findings two years after ventriculographic examination. The
      LVEF recovered to > or = 50% in 10 patients (Group A), while it was sustained at
      < 50% in 10 patients (Group B). The clinical features of each group were
      compared, based on results of physical examination, radionuclide
      ventriculography, and other diagnostic tests performed on their referral to
      hospital. Only the systolic blood pressure differed significantly between the two
      groups, being slightly, but significantly, increased in Group A over that in
      Group B (P < 0.05). LVEF at rest by radionuclide did not differ (Group A: 31.5 +/
      10.3% vs Group B: 26.5 +/- 9.4%). Peak exercise EF-EF at rest (peak delta EF) in
      Group A was apparently increased (3.4 +/- 4.0%), while that in Group B was
      decreased (-4.4 +/- 5.2%). The positive peak delta EF had a highly predictive
      value of 90% for patients with DCM whose LVEF will recover to more than 50%. The
      recovery EF-EF at rest did not differ significantly between groups (Group A: 8.4
      +/- 4.7 vs Group B: 3.9 +/- 2.3, P < 0.05). Other clinical parameters such as
      functional class, cardiothoracic ratio, LVEF by echocardiography, cardiac index
      by Swan-Ganz catheter examination, and histologic examination of biopsied
      endocardium were indistinguishable in the two groups. The authors conclude that
      peak delta EF of radionuclide ventriculography on exercise indicates a
      preservation of LVEF and predicts a good clinical recovery in patients with DCM.

PMID- 9194534
TI  - Management of abdominal aortic prosthetic graft infection requiring emergent
      treatment.
AB  - The purpose of this study was to investigate mortality and morbidity rates and
      long-term outcome of patients who underwent emergency treatment of abdominal
      aortic prosthetic graft infection. Between January 1984 and December 1993, 18 men
      aged fifty-nine +/- sixteen years were operated on as an emergency for an acute
      life-threatening complication of aortic prosthetic graft infection. The grafts
      had been implanted for abdominal aortic aneurysm in 9 patients and aortoiliac
      occlusive disease in 9, from one to one hundred seventy months previously. Five
      (28%) patients presented with a hemorrhagic shock due to a fistula between the
      vascular reconstruction and the small bowel (4 patients) or the right ureter (1
      patient) and 13 (72%) had generalized sepsis. The grafts were always radically
      explanted. Extraanatomic revascularization procedures included 6 axillopopliteal
      and 12 axillofemoral bypass grafts. Operative mortality was 39% (7 patients), and
      3 (9%) limbs were amputated within thirty days. Two (11%) patients died after
      seven and twelve months, respectively, of septic complications, and 1 (5%)
      patient died after six months from an unrelated cause. Eight (73%) patients are
      still alive at a mean follow-up of fifty +/- thirty-four months, but in 3 the
      extraanatomic bypass was removed for infection and 5 major amputations were
      performed. Two-year survival and limb salvage rates were 44% and 50%,
      respectively. Aortic prosthetic graft infections that require emergent treatment
      continue to demonstrate high early and late mortality and limb loss rates despite
      aggressive intervention and limb salvage procedures. Newer methods of managing
      these complications should continue to be investigated.

PMID- 9194536
TI  - Effects of insulin and the combination of insulin plus metformin (glucophage) on
      microvascular reactivity in control and diabetic hamsters.
AB  - The purpose of this study was to determine the in vivo microvascular reactivity
      of arterioles (mean internal diameter range: 16.0 to 106.4 microm) and venules
      (mean internal diameter range: 24.0 to 117.3 microm) in the hamster cheek pouch
      to insulin and to the mixture insulin + metformin. Experiments were performed
      using an intravital microscope coupled to a closed-circuit TV system and a
      videotape. The TV monitor display was used to obtain arteriolar and venular
      internal diameter measurements by an image-shearing device. The studied drugs
      were applied topically, added to the superfusion solution, to avoid systemic
      effects that would complicate the analysis of the results. In control animals
      (glycemia 7.7 +/- 0.4 mmol/L), application of insulin (10 to 500 microU/mL/min)
      evoked vasodilatation in a dose-dependent fashion in arterioles (4.9 +/- 3.2% to
      50.9 +/- 6.5%, smallest and largest concentration, respectively, values expressed
      in percent of the initial diameter as mean +/- SE) and venules (-2.1 +/- 3.1% to
      14.3 +/- 5.1%), decreased and finally abolished the spontaneous vasomotion
      frequency (from 9.5 +/- 0.3 cycles per minute [cpm] to 0.0 +/- 0.0 cpm) and
      amplitude (from 8.6 +/- 0.3 to 0.0 +/- 0.0 microm). Addition of metformin, 0.2
      mg/mL/min, did not significantly change either the observed vasodilatation in
      arterioles and venules or the vasomotion frequency and amplitude curves. Two
      types of diabetic hamsters were studied: severely diabetic, induced with three
      intraperitoneal injections of streptozotocin, diluted in physiological saline, 50
      mg/kg/dose, given in three consecutive days, and mildly diabetic, induced by a
      single dose of streptozotocin. All diabetic animals were studied four weeks after
      the onset of diabetes and no specific treatment for diabetes was given. In
      severely diabetic hamsters (glycemia 18.0 +/- 2.2 mmol/L), application of
      insulin, in the same concentration range, evoked a significantly reduced
      vasodilatation in arterioles as compared with control animals (5.9 +/- 1.3% to
      18.9 +/- 3.5%) and did not change the vasodilatation observed in the venules (5.9
      +/- 1.4% to 21.3 +/- 2.5%). In these preparations no spontaneous arteriolar
      vasomotion could be detected. Addition of metformin did not significantly improve
      the impaired vasodilatation. In mildly diabetic hamsters (glycemia 12.1 +/- 0.8
      mmol/L), application of insulin, in the same concentration range, evoked
      vasodilatation, in a dose-dependent fashion, equivalent to the one observed in
      control animals, in arterioles (3.1 +/- 2.5% to 53.4 +/- 10.0%) and venules (7.1
      +/- 3.0% to 29.9 +/- 4.8%) and also reduced the vasomotion frequency (from 10.1
      +/- 0.3 to 0.1 +/- 0.1 cpm) and amplitude (from 9.2 +/- 0.6 to 0.2 +/- 0.2
      microm). Addition of metformin tended to increase the observed arteriolar
      dilatation (6.6 +/- 3.0% to 67.8 +/- 5.5%), did not change the venular dilatation
      (6.7 +/- 4.8% to 28.0 +/- 3.3%), and tended to preserve vasomotion frequency and
      amplitude. These experiments show that (1) insulin has a direct dilatatory effect
      on arterioles and venules; (2) the vasodilatation evoked by insulin is impaired
      in severe diabetes, and (3) no significant abnormality could be detected on
      microvascular reactivity in mild diabetes. Further addition of metformin helped
      to maintain the spontaneous arteriolar vasomotion even during moderate
      vasodilatation and tended to augment the arteriolar dilatation evoked by insulin
      in mildly diabetic animals.

PMID- 9194537
TI  - Effects of nisoldipine on cytosolic calcium, platelet aggregation, and
      coagulation/fibrinolysis in patients with coronary artery disease.
AB  - The effect of nisoldipine, a dihydropyridine Ca2+ antagonist, on the platelet
      cytosolic Ca2+ concentration ([Ca2+]i), platelet aggregation, and various
      coagulation and fibrinolysis parameters was assessed in normotensive patients
      with coronary artery disease (CAD). Eleven patients with angiographically
      confirmed CAD (4 men, 7 women aged 67.3 +/- 5.4 years) were administered
      nisoldipine at 10 mg/day for two weeks. The [Ca2+]i was determined by use of
      fura2-loaded platelets, platelet aggregation was measured with an aggregometer,
      and coagulation/fibrinolysis parameters were measured by standard methods.
      Nisoldipine did not significantly affect blood pressure or heart rate. However,
      the [Ca2+]i decreased significantly (P<0.05) and platelet aggregation was also
      significantly inhibited. Plasma D-dimer levels decreased significantly (P<0.01).
      Thus, nisoldipine not only suppressed platelet activation but also affected the
      coagulation system, suggesting that it is not only a vasodilator and platelet
      inhibitor but also an antithrombotic agent.

PMID- 9194538
TI  - Duplex sonography of venous stasis.
AB  - The major reasons for venous thrombosis are inflammation, increased blood
      coagulability, and blood stasis. Investigation of these processes in vivo in a
      particular vein is difficult. Blood stasis in the peripheral veins is assumed to
      increase the risk of thrombosis during immobilization. By duplex sonography the
      authors were able to demonstrate different echogenicity in single veins of the
      lower limb in healthy subjects in a sitting position. Of 25 subjects, 7 presented
      a high echogenicity of the venous blood similar to that of the surrounding
      tissue. An additional 5 subjects presented this phenomenon after venous blood
      flow was stopped by a pressure cuff. The remaining 13 subjects still presented a
      dark lumen of the veins. Duplex sonography can discriminate different
      compositions of resting venous blood associated with venous stasis. Whether these
      findings correlate with an increased risk of thrombosis is not known.

PMID- 9194539
TI  - A case of favorable dilation of protected left main coronary artery lesion
      achieved through performance of adjunctive DCA on residual stenosis following use
      of rotablator.
AB  - It is believed that directional coronary atherectomy (DCA) is more suitable than
      percutaneous transluminal coronary angioplasty for lesions such as severe
      eccentric lesions, ostial lesions, and branch lesions. However, it remains a fact
      that lesions that are also highly calcified are often suboptimal, since there may
      be difficulties such as in insertion of the housing and in sufficient cutting and
      removal. On the other hand, Rotablator is effective on calcified lesions, but
      afterward, dilation by balloon angioplasty for residual stenosis becomes
      necessary in many cases. This is a report of the authors' experience on an
      interesting case in which favorable dilation of a lesion in the protected left
      main coronary artery (LMCA) was achieved by using Rotablator after confirmation
      of a high degree of calcification by means of intravascular ultrasound (IVUS)
      echocardiograhy, followed by the performance of DCA on the residual stenosis.

PMID- 9194540
TI  - Transcranial Doppler velocities in patients with thromboangiitis obliterans.
AB  - The idea of cerebrovascular injury in cases of thromboangiitis obliterans was not
      strange to Leo Buerger, but Jager (1932), as well Lindenberg and Spatz (1939),
      first established it. The aim of this study was to investigate the hemodynamics
      in the basal cerebral arteries by means of transcranial Doppler in patients with
      thromboangiitis obliterans. Thirty patients (all men; average age 40.03 +/- 16.4
      years) were included--one group twenty-four to forty years of age and another
      group forty-one to fifty years of age. The results show that the blood flow
      velocities in middle and anterior cerebral arteries in both groups of patients
      were significantly lower than in healthy persons. The trends towards reduction of
      blood flow velocity were also evident in posterior cerebral arteries. The authors
      describe in detail 2 patients who suffered major ischemic stroke. Cerebrovascular
      disorders in Buerger's disease are probably more frequent than supposed and have
      to be taken into account.

PMID- 9194542
TI  - Simultaneous multiple brain hemorrhage associated with migraine--a case report.
AB  - A fifty-five-year-old woman with a history of migraine suddenly developed an
      occipital headache and visual disturbance after a typical migrainous attack. On
      admission, she had a left homonymous hemianopsia, and computed tomography of the
      brain demonstrated intracranial hematomas in the occipital subcortices
      bilaterally. Cerebral arteriography revealed diffuse vasospasm of the
      intracranial arteries attributed to the migraine. The cystatin C concentration in
      the cerebrospinal fluid was low, which suggested the existence of cerebral
      amyloid angiopathy. According to the clinical course and angiographic findings,
      it is suggested that the vasospasm associated with migraine played an important
      role in developing multiple brain hemorrhage in this patient.

PMID- 9194543
TI  - Not everything is in the genes.

PMID- 9194541
TI  - Cholera and myocarditis--a case report.
AB  - The authors describe the case of a fifty-nine-year-old white man, previously in
      good health, who initiated his present illness with acute episode of
      enterocolitis characterized by mild fever and, in the next eight hours, twenty
      four episodes of watery diarrhea, nausea and vomiting, as well as generalized
      sweating and severe weakness secondary to hypovolemia and electrolyte disorder.
      These complications were corrected in seventy-two hours in the intensive care
      unit. Two days later, when the patient was stable hemodynamically, under cardiac
      monitoring and with normal laboratory studies including serum electrolytes, he
      developed electrocardiographic changes characterized by trifascicular block
      (prolonged P-R interval, complete right bundle branch block [CRBBB] and left
      posterior hemiblock [LPH]) with a cardiac rate of thirty beats per minute, for
      which a temporary pacemaker was inserted. Endomyocardial biopsy showed
      histopathologic signs of myocarditis and the immunologic study of the cardiac
      tissue revealed positive polymerize chain reaction (PCR+) with the presence of
      antitoxine choleric antibodies (AcTCA). After three weeks, the same conduction
      disturbances remained, for which a permanent pacemaker was inserted. On top of
      intravenous fluid replacement and electrolyte supplements, the patient was
      managed with tetracycline 2 g a day for one week and sulfamethoxazole
      trimethoprim 800/160 mg a day for two weeks. The purpose of this study is to
      present a rare and very well-documented myocarditis by cholera in a patient with
      enteric disease, in whom several cardiac complications occurred.

PMID- 9194544
TI  - A lesson on preparedness.

PMID- 9194545
TI  - NIH backers take Clinton to task over impact of budget pact.

PMID- 9194546
TI  - Republicans seek to widen cloning ban.

PMID- 9194547
TI  - Palaeontologists protest at Web sale of hominid remains.

PMID- 9194548
TI  - Brussels reshapes science panels after BSE criticism.

PMID- 9194549
TI  - Fraud claims shake German complacency.

PMID- 9194550
TI  - Is cloning an attack on human dignity?

PMID- 9194551
TI  - Protect patients' rights.

PMID- 9194552
TI  - Experimental psychology. In a blink of the mind's eye.

PMID- 9194553
TI  - Demography. Taking the measure of uncertainty.

PMID- 9194554
TI  - Keith Roberts Porter (1912-97)

PMID- 9194555
TI  - DNA fingerprints from fingerprints.

PMID- 9194556
TI  - How many replicons make a nodule?

PMID- 9194557
TI  - Unique morphology of the human eye.

PMID- 9194558
TI  - Double identity for proteins of the Bcl-2 family.
AB  - Bcl-2 is an oncogenic protein that acts by inhibiting programmed cell death. The
      mechanisms used by this and related anti-apoptotic proteins to protect cells from
      cytotoxic stimuli are now emerging, with the discovery that Bcl-2 can function
      both as an ion channel and as an adaptor or docking protein.

PMID- 9194559
TI  - Doubling of world population unlikely.
AB  - Most national and international agencies producing population projections avoid
      addressing explicitly the issue of uncertainty. Typically, they provide either a
      single projection or a set of low, medium and high variants, and only very rarely
      do they give these projections a probabilistic interpretation. Probabilistic
      population projections have been developed for specific industrialized countries,
      mostly the United States, and are based largely on time-series analysis. On a
      global level, time-series analysis is not applicable because there is a lack of
      appropriate data, and for conceptual reasons such as the structural discontinuity
      caused by the demographic transition. Here we report on a new probabilistic
      approach that makes use of expert opinion on trends in fertility, mortality and
      migration, and on the 90 per cent uncertainty range of those trends in different
      parts of the world. We have used simulation techniques to derive probability
      distributions of population sizes and age structures for 13 regions of the world
      up to the year 2100. Among other things, we find that there is a probability of
      two-thirds that the world's population will not double in the twenty-first
      century.

PMID- 9194560
TI  - Attentional requirements in a 'preattentive' feature search task.
AB  - It is commonly assumed that certain features are so elementary to the visual
      system that they require no attentional resources to be perceived. Such
      'preattentive' features are traditionally identified by visual search
      performance, in which the reaction time for detecting a feature difference
      against a set of distractor items does not increase with the number of
      distractors. This suggests an unlimited capacity for the perception of such
      features. We provide evidence to the contrary, demonstrating that detection of
      differences in a simple feature such as orientation is severely impaired by
      additionally imposing an attentionally demanding rapid serial visual presentation
      task involving letter identification. The same visual stimuli exhibit non
      increasing reaction time versus set-size functions. These results demonstrate
      that attention can be critical even for the detection of so-called 'preattentive'
      features.

PMID- 9194561
TI  - Restricted attentional capacity within but not between sensory modalities.
AB  - Restrictions to attentional capacity are revealed by the interference that
      commonly results when two sensory inputs must be identified at the same time. To
      investigate this phenomenon within and between modalities, we presented streams
      of visual and/or auditory inputs, containing occasional targets to be identified
      and recalled. For two visual or two auditory streams, identification of one
      target produced a sustained reduction in the ability to identify a second, the
      period of interference lasting for several hundred milliseconds. Subjectively,
      when attention was assigned to one target it was temporarily unavailable for
      another. In contrast, there was no such time-locked interference between targets
      in different modalities. The results suggest a modality-specific restriction to
      concurrent attention and awareness; visual attention to one simple target does
      not restrict concurrent auditory attention to another.

PMID- 9194562
TI  - The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle
      fusion.
AB  - The Rab family of low-molecular-mass GTP-binding proteins are thought to guide
      membrane fusion between a transport vesicle and the target membrane, and to
      determine the specificity of docking. The docking and fusion of vesicles is,
      however, a complex multistep reaction, and the precise point at which Rab
      proteins act in these sequential processes is unknown. In brain, the Rab protein
      Rab3A is specific to synaptic vesicles, whose exocytosis can be monitored with
      submillisecond resolution by following synaptic transmission. We have now
      determined the precise point at which Rab3A acts in the sequence of synaptic
      vesicle docking and fusion by using electrophysiological analysis of
      neurotransmitter release in Rab3A-deficient mice. Unexpectedly, the size of the
      readily releasable pool of vesicles is normal, whereas Ca2+-triggered fusion is
      altered in the absence of Rab3A in that a more-than-usual number of exocytic
      events occur within a brief time after arrival of the nerve impulse.

PMID- 9194563
TI  - C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal
      inhibitory peptide to GTPases.
AB  - The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family
      GTPases. The inhibitory activity of GDI derives both from an ability to bind the
      carboxy-terminal isoprene of Rho family members and extract them from membranes,
      and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here
      we demonstrate that these binding and inhibitory functions of rhoGDI can be
      attributed to two structurally distinct regions of the protein. A carboxy
      terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds
      strongly to the Rho-family member Cdc42, yet has little effect on the rate of
      nucleotide dissociation from the GTPase. The solution structure of this domain
      shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes,
      and an exposed surface that interacts with the protein portion of Cdc42. The
      amino-terminal region of rhoGDI is unstructured in the absence of target and
      contributes little to binding, but is necessary to inhibit nucleotide
      dissociation from Cdc42. These results lead to a model of rhoGDI function in
      which the carboxy-terminal binding domain targets the amino-terminal inhibitory
      region to GTPases, resulting in membrane extraction and inhibition of nucleotide
      cycling.

PMID- 9194564
TI  - Synergistic activation of transcription by CBP and p53.
AB  - The tumour suppressor p53 is a transcriptional regulator whose ability to inhibit
      cell growth is dependent upon its transactivation function. Here we demonstrate
      that the transcription factor CBP, which is also implicated in cell proliferation
      and differentiation, acts as a p53 coactivator and potentiates its
      transcriptional activity. The amino-terminal activation domain of p53 interacts
      with the carboxy-terminal portion of the CBP protein both in vitro and in vivo.
      In transfected SaoS-2 cells, CBP potentiates activation of the mdm-2 gene by p53
      and, reciprocally, p53 potentiates activation of a Gal4-responsive target gene by
      a Gal4(1-147)-CBP(1678-2441) fusion protein. A double point mutation that
      destroys the transactivation function of p53 also abolishes its binding to CBP
      and its synergistic function with CBP. The ability of p53 to interact physically
      and functionally with a coactivator (CBP) that has histone acetyltransferase
      activity and with components (TAFs) of the general transcription machinery
      indicates that it may have different functions in a multistep activation pathway.

PMID- 9194565
TI  - Binding and modulation of p53 by p300/CBP coactivators.
AB  - The adenovirus E1A and SV40 large-T-antigen oncoproteins bind to members of the
      p300/CBP transcriptional coactivator family. Binding of p300/CBP is implicated in
      the transforming mechanisms of E1A and T-antigen oncoproteins. A common region of
      the T antigen is critical for binding both p300/CBP and the tumour suppressor
      p53, suggesting a link between the functions of p53 and p300. Here we report that
      p300/CBP binds to p53 in the absence of viral oncoproteins, and that p300 and p53
      colocalize within the nucleus and coexist in a stable DNA-binding complex.
      Consistent with its ability to bind to p300, E1A disrupted functions mediated by
      p53. It reduced p53-mediated activation of the p21 and bax promoters, and
      suppressed p53-induced cell-cycle arrest and apoptosis. We conclude that members
      of the p300/CBP family are transcriptional adaptors for p53, modulating its
      checkpoint function in the G1 phase of the cell cycle and its induction of
      apoptosis. Disruption of p300/p53-dependent growth control may be part of the
      mechanism by which E1A induces cell transformation. These results help to explain
      how p53 mediates growth and checkpoint control, and how members of the p300/CBP
      family affect progression from G1 to the S phase of the cell cycle.

PMID- 9194566
TI  - Structure of isopenicillin N synthase complexed with substrate and the mechanism
      of penicillin formation.
AB  - The biosynthesis of penicillin and cephalosporin antibiotics in microorganisms
      requires the formation of the bicyclic nucleus of penicillin. Isopenicillin N
      synthase (IPNS), a non-haem iron-dependent oxidase, catalyses the reaction of a
      tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV), and dioxygen
      to form isopenicillin N and two water molecules. Mechanistic studies suggest the
      reaction is initiated by ligation of the substrate thiolate to the iron centre,
      and proceeds through an enzyme-bound monocyclic intermediate. Here we report the
      crystal structure of IPNS complexed to ferrous iron and ACV, determined to 1.3 A
      resolution. Based on the structure, we propose a mechanism for penicillin
      formation that involves ligation of ACV to the iron centre, creating a vacant
      iron coordination site into which dioxygen can bind. Subsequently, iron-dioxygen
      and iron-oxo species remove the requisite hydrogens from ACV without the direct
      assistance of protein residues. The crystal structure of the complex with the
      dioxygen analogue, NO and ACV bound to the active-site iron supports this
      hypothesis.

PMID- 9194567
TI  - Presence of multiple functional polyadenylation signals in the 3'-untranslated
      region of human corticotropin receptor cDNA.
AB  - We present 2.59 kb of the 3'-non-coding region of the ACTH receptor cDNA that
      contains seven potential polyadenylation signals. Among these signals, five are
      functional as detected by 3'-RACE and are consistent with the transcripts of 1.8,
      3.4 and 4 kb visualized on Northern blots. We propose that the most likely
      molecular mechanism for the multiple ACTH-R mRNA transcripts is the alternative
      use of polyadenylation signals.

PMID- 9194568
TI  - Isolation of a Xenopus laevis genomic clone representing a novel N-cadherin
      related gene.
AB  - We have isolated a Xenopus laevis genomic sequence distinct from, but sharing
      high sequence similarity with N-cadherin. We present evidence that the gene
      represented by this sequence, named XNcad3, resides at a separate locus to the
      two previously isolated N-cadherin clones from this species. Extensive analysis
      could detect no expression of XNcad3 in embryonic or adult tissues. It seems
      likely that XNcad3 represents a non-expressed pseudogene, or perhaps a novel
      cadherin with a restricted expression pattern.

PMID- 9194569
TI  - Tyrosine phosphorylation-and epidermal growth factor-dependent regulation of the
      sodium-coupled amino acid transporter B0 in the human placental choriocarcinoma
      cell line JAR.
AB  - We have recently cloned an amino acid transporter from the human placental
      choriocarcinoma cell line JAR which, when functionally expressed in HeLa cells,
      induces an amino acid transport activity with characteristics known to be
      associated with the amino acid transport system B(0) (R. Kekuda, P.D. Prasad,
      Y.J. Fei, V. Torres-Zamorano, S. Sinha, T.L. Yang-Feng, F.H. Leibach, and V.
      Ganapathy, J. Biol. Chem. 271, 18657-18661, 1996). The presence of the amino acid
      transport system B(0) (ATB(0)) has however not been previously described in these
      cells by functional studies. In the present investigation, we have obtained
      evidence for the existence of ATB(0) in JAR cells and delineated the functional
      characteristics of the transporter. The identifying characteristics include Na(+)
      dependence and preference for neutral amino acids. In addition, we have used the
      JAR cells as a model system to investigate the regulatory aspects of ATB(0).
      Treatment of the cells with the neuroprotective agent aurintricarboxylic acid
      (ATA) for 16 h leads to a significant increase in ATB(0) activity. This increase
      is associated with enhanced maximal velocity of the transporter and with
      increased steady state levels of the transporter mRNA. The effect of ATA is
      blocked by the tyrosine kinase inhibitor genistein. ATA treatment results in
      increased tyrosine phosphorylation of two major proteins, 180 kDa and 140 kDa in
      size. The 180 kDa protein is likely to be the epidermal growth factor (EGF)
      receptor because exposure of the cells to EGF also leads to enhanced tyrosine
      phosphorylation of a protein of similar molecular size. Furthermore, the effects
      of ATA on ATB(0) activity and on ATB(0) mRNA levels can be reproduced by EGF.
      Treatment of the cells with EGF for 24 h results in a significant increase in
      ATB(0) activity and this effect is associated with an increase in the maximal
      velocity of the transporter and with an increase in the steady state levels of
      the transporter mRNA. These data suggest that ATA influences ATB(0) activity in
      JAR cells most likely by activating the EGF receptor through tyrosine
      phosphorylation. It is concluded that the human placental choriocarcinoma cells
      functionally express the amino acid transport system B(0) and that the expression
      of the system in these cells is stimulated by EGF.

PMID- 9194570
TI  - Suppression of basement membrane type IV collagen degradation and cell invasion
      in human melanoma cells expressing an antisense RNA for MMP-1.
AB  - During progression from benign nevus to vertical growth phase melanoma,
      melanocytes acquire the ability to invade into the dermis. This process requires
      rupture of the basal lamina and dissolution of dermal type I collagen. Metastases
      derived human melanoma MIM cells have an invasive ability in vitro which is
      dependent on metalloproteinases. In the present study we analysed the role of
      type I collagenase (MMP-1) in melanoma invasion using MIM cells in which the
      constitutive expression of MMP-1 was suppressed by stable transfection with a
      plasmid vector expressing a 777 bp antisense fragment of MMP-1 genomic DNA. Two
      clones were isolated in which MMP-1 mRNA expression was blocked by 90-96% with a
      corresponding loss in protein synthesis. In their morphological appearance and
      growth rate in vitro these cells were indistinguishable from wild type cells or
      control cells transfected with the same vector expressing the MMP-1 fragment in
      the sense orientation. Their mRNA and protein levels for type IV collagenase (MMP
      2) were unchanged as assessed by Northern and Western blot analyses and by
      gelatin zymography. However, when the invasive ability of the cells was measured,
      we found that in addition to type I collagen, invasion through type IV collagen
      and a reconstituted, type IV collagen-containing basement membrane (Matrigel)
      were also significantly inhibited as compared to normal or sense-transfected
      cells. The results indicate that despite the presence of functional MMP-2,
      degradation of type IV collagen matrices by the melanoma cells was dependent on
      expression of MMP-1.

PMID- 9194571
TI  - Decreased transcript expression coincident with impaired glycosylation in the
      beta2-adrenergic receptor gene does not result from differences in the primary
      sequence.
AB  - Variants of the S49 mouse lymphoma cell line exhibit multiple lesions along the
      pathway of cyclic AMP generation in response to beta2-adrenergic stimulation. Two
      such variants, beta(p) and beta(d), are characterized by decreased receptor
      binding and mRNA expression, 50% and 25% of wild-type receptor expression,
      respectively. The rate of beta2-adrenergic receptor synthesis was measured and
      found to be decreased in the beta d cells vis-a-vis the rate in wild type cells.
      The molecular mass of the beta2-adrenergic receptor in the S49 wild-type, beta(p)
      and beta(d) variant cells was estimated by labeling the receptor with the
      photoaffinity probe [125I]iodocyanopindololdiazirine. Receptor size was found to
      be 67,000 and 47,000 Da in the wild-type and 60,000 and 42,000 in the two variant
      cells. This 6 kDa discrepancy in mass was abolished upon treatment of labeled
      cell extracts with N-glycosidase F, suggesting the possibility of either N
      terminal truncation or altered glycosylation of the receptor in the variant
      cells. To distinguish between these possibilities, we sequenced the beta2
      adrenergic receptor gene and two kilobases of the 5'-non-coding region. No
      differences were found in the coding region of the gene from wild-type, beta(p)
      and beta(d) S49 cells suggesting that both the diminished expression and the
      decreased size of beta2-adrenergic receptor in the beta(p) and beta(d) S49
      variants are related to impaired glycosylation of the receptor. This hypothesis
      was substantiated by the reduced retention of the variant cells' beta2-adrenergic
      receptor on immobilized WGA. Furthermore, growth of the S49 cells in the presence
      of the alpha-mannosidase II inhibitor, swainsonine, preferentially impaired the
      ability of the receptors derived from the variant cells to bind to WGA. These
      results imply that altered expression and glycosylation of G-protein-linked
      receptors occur as a consequence of one or more mutations outside the receptor's
      open reading frame.

PMID- 9194572
TI  - Catecholamines are required for androgen-induced ODC expression but not for
      hypertrophy of mouse kidney.
AB  - Catecholamine depletion, evoked by reserpine, dramatically impaired (5-fold) the
      testosterone-induced increase of ornithine decarboxylase (ODC) activity in female
      mouse kidney. However, reserpine did not prevent kidney hypertrophy evoked by
      testosterone. This is evidenced by the activity of sensitive, biochemical markers
      of renal hypertrophy, namely arginase and ornithine aminotransferase (OAT), that
      responded with the increase and decrease of activities to testosterone treatment,
      respectively. Arginine and ornithine, substrates and/or products of marker
      enzymes, showed a striking homeostasis as their level was not affected by
      testosterone and reserpine, and only slightly by DFMO. Northern blot analysis
      revealed that the ODC mRNA level, that was increased 10-fold by testosterone, was
      decreased 2-fold in catecholamine-depleted hypertrophic kidney. Thus, ODC
      transcript level, lowered by reserpine, correlated partially with an attenuated
      response of ODC activity to testosterone. This was in contrast to DFMO, which
      inhibited ODC activity, but significantly increased its mRNA content. It is
      concluded that catecholamines could be involved together with testosterone in
      regulation of the ODC gene expression in mouse kidney.

PMID- 9194573
TI  - Cloning and functional analysis of a polymorphic variant of the ovine Mel 1a
      melatonin receptor.
AB  - We have isolated a novel variant of the Mel 1a melatonin receptor from an ovine
      PT cDNA library. Relative to the reported sequence for the Mel 1a melatonin
      receptor there are 8 changes in the DNA sequence. Only 3 of these result in amino
      acid substitutions, one in extracellular loop 3 and two in the carboxy-terminal
      tail. We have designated the novel variant of the sheep Mel 1a receptor Mel
      1a(beta), and correspondingly the previously reported variant Mel 1a(alpha). As
      minor changes in the primary amino acid sequence of G-protein-coupled receptors
      can influence their functional characteristics we have accordingly characterized
      this novel variant of the Mel 1a melatonin receptor. This melatonin receptor
      displays high affinity binding and inhibits the cAMP second messenger pathway in
      transfected L-cells demonstrating that this receptor is fully functional. PCR
      analysis shows Mel 1a(beta) is present in several breeds of sheep and suggests
      that the Mel 1a(beta) receptor was established early in the evolution of the
      sheep species.

PMID- 9194574
TI  - Dissociation of tyrosine phosphorylation and activation of phosphoinositide
      phospholipase C induced by the protein kinase C inhibitor Ro-31-8220 in Swiss 3T3
      cells treated with platelet-derived growth factor.
AB  - Platelet-derived growth factor (PDGF) stimulates the hydrolysis of
      phosphatidylinositol 4,5-bisphosphate (Ptd InsP2) via phospholipase C-gamma1 (PLC
      gamma1) in Swiss 3T3 cells. Treatment of cells with the protein kinase C (PKC)
      inhibitor Ro-31-8220 greatly decreased PDGF-induced tyrosine phosphorylation of
      PLC-gamma1, but paradoxically enhanced the production of inositol phosphates
      (InsPs). The inhibitor also caused an increase of PDGF receptor tyrosine
      phosphorylation at later times. The changes in phosphorylation of the receptor
      were correlated with alterations in PLC-gamma1 translocation to the particulate
      fraction. Thus, although activation of PLC-gamma1 was associated with
      phosphorylation of the receptor and translocation of the enzyme to the
      particulate fraction, it was dissociated from its tyrosine phosphorylation. A non
      receptor-associated, cytosolic tyrosine kinase also was found to phosphorylate
      PLC-gamma1 in a PDGF-dependent manner, but was not inhibited by Ro-31-8220 in
      vitro. PKC depletion by phorbol ester treatment decreased the tyrosine
      phosphorylation of PLC-gamma1 induced by PDGF and slowed the translocation of PLC
      gamma1, but Ro-31-8220 produced further effects. The effect of Ro-31-8220 to
      enhance the production of InsPs could not be attributed to inhibition of PKC
      since InsPs production with PDGF was decreased in PKC-depleted cells and a
      stimulatory effect of the inhibitor was still evident. Interestingly, Ro-31-8220
      decreased the radioactivity in phosphatidylinositol and increased that in
      phosphatidylinositol 4-phosphate and PtdInsP2 in cells labeled with
      myo[3H]inositol. The increased synthesis of PtdInsP2 could contribute to the
      increased production of InsPs induced by Ro-31-8220. In summary, these results
      support the conclusion that the activation of PLC-gamma1 in response to PDGF
      requires autophosphorylation of the receptor and membrane association of PLC
      gamma1, but not phosphorylation of the enzyme. Furthermore, the effects of Ro-31
      8220 on the tyrosine phosphorylation and activity of PLC-gamma1, and on PtdInsP2
      synthesis cannot be attributed to inhibition of PKC.

PMID- 9194575
TI  - The thrombin receptor in adrenal medullary microvascular endothelial cells is
      negatively coupled to adenylyl cyclase through a Gi protein.
AB  - The effects of thrombin on adenylyl cyclase activity were examined in rat adrenal
      medullary microvascular endothelial cells (RAMEC). Confluent RAMEC monolayers
      were stimulated for 5 min with cAMP-generating agents in the absence and presence
      of thrombin, and intracellular cAMP was measured with a radioligand binding
      assay. Thrombin (0.001-0.25 U/ml) dose-dependently inhibited IBMX-, isoproterenol
      and forskolin-stimulated cAMP accumulation. A peptide agonist of the thrombin
      receptor, gamma-thrombin, and the serine proteases trypsin and plasmin, also
      inhibited agonist-stimulated cAMP levels, while proteolytically inactive PPACK-
      or DIP-alpha-thrombins were without effect. Moreover, the thrombin inhibitor
      hirudin abolished the inhibitory effect of thrombin but not of the peptide
      agonist. These results suggest that the inhibitory action of thrombin on cAMP
      accumulation is mediated by a proteolytically-activated thrombin receptor. The
      inhibitor of G(i)-proteins pertussis toxin abolished the inhibitory effect of
      thrombin on isoproterenol- or IBMX-stimulated cAMP production, while the phorbol
      ester PMA partly impaired it. The protein kinase C inhibitors staurosporine or H7
      and the intracellular Ca2+ chelator BAPTA-AM were without effect. Collectively,
      our data suggest that the thrombin receptor in RAMEC is negatively coupled to
      adenylyl cyclase through a pertussis toxin-sensitive G(i)-protein.

PMID- 9194576
TI  - Inhibition of protein tyrosine kinases or protein kinase C prevents nonspecific
      killer T lymphocyte-mediated tumoricidal activity.
AB  - The signal transduction events which govern major histocompatibility complex
      unrestricted tumour cell destruction by nonspecific killer T lymphocytes induced
      with anti-CD3 antibody have not yet been determined. In this study we used
      pharmacologic inhibitors to investigate the role of protein tyrosine kinases
      (PTK) and protein kinase C (PKC) in this process. The PTK-inhibitors herbimycin
      A, genistein, and methyl 2,5-dihydroxycinnamate blocked anti-CD3-activated killer
      T (AK-T) lymphocyte-mediated killing of tumour target cells. The PKC-inhibitors
      staurosporine, calphostin C, and myristoylated PKC pseudosubstrate peptide, as
      well as PKC desensitization by phorbol 12-myristate 13-acetate pretreatment, also
      suppressed the cytolytic effector function of AK-T lymphocytes. Lack of
      tumoricidal activity was not due to reduced AK-T lymphocyte binding to tumour
      target cells but was associated with the abrogation of granule exocytosis,
      indicating that PTK and PKC are involved in the postbinding process which results
      in delivery of the 'lethal hit' by AK-T lymphocytes.

PMID- 9194577
TI  - The gastrin-releasing peptide receptor is differentially coupled to adenylate
      cyclase and phospholipase C in different tissues.
AB  - Recent studies suggest that in some tissues GRP receptor activation can both
      stimulate phospholipase C and the adenylate cyclase pathway and that activation
      of the latter pathway may be important in mediating some of its well-described
      growth effects. However, other studies suggest GRP-R may not be coupled to
      adenylate cyclase. To investigate this possibility, in the present study we
      determined the coupling of the GRP receptors to each pathway in mouse, rat, and
      guinea pig pancreatic acini and compared it to that in mouse Swiss 3T3 cells and
      human SCLC cells, all of which possess well-characterized GRP receptors.
      Moreover, we tested the effect of PKC activation on the ability of GRP-related
      peptides to increase cAMP accumulation in these tissues. Changes in cAMP levels
      were determined with or without IBMX present, with or without forskolin, or both
      to amplify small increases in cAMP. In mouse, rat and guinea pig pancreatic
      acini, murine Swiss 3T3 cells and human SCLC cells, GRP-related peptides caused a
      600%, 500%, 250%, 300% and 60% increase, respectively, in [3H]IP with 1-3 nM
      causing a half-maximal effect. In murine Swiss 3T3 cells, IBMX, forskolin, and
      IBMX plus forskolin caused a 300%, 3500% and 10500% increase in cAMP,
      respectively. GRP-related peptides and VIP caused an additional 70% increase in
      cAMP with GRP causing a half-maximal (EC50) increase in cAMP at 2.1 +/- 0.5 nM,
      which was not significantly different from the EC50 of 3.1 +/- 0.9 nM for
      increasing [3H]IP in these cells. GRP-related peptides did not stimulate
      increases in cAMP in mouse, rat or guinea pig pancreatic acini or in SCLC cells
      either alone, with IBMX or forskolin or both. However, in pancreatic acini IBMX,
      forskolin or both increased cAMP 3 to 8-, 10 to 500-, and 100 to 1000-fold
      increase and the addition of VIP caused an additional 20-, 2-, and 3-fold
      increase in cAMP in the different species. In mouse pancreatic acini with TPA
      alone or IBMX plus TPA, neither bombesin nor GRP increased cAMP. Furthermore, in
      mouse pancreatic acini, neither TPA nor TPA plus IBMX altered basal or VIP
      stimulated increases in cAMP. In mouse Swiss 3T3 cells TPA significantly
      increased cAMP stimulated by Bn, GRP or VIP. These results demonstrated that GRP
      receptor activation in normal tissues from three different species and a human
      tumoral cell line do not result in adenylate cyclase activation, whereas in Swiss
      3T3 cells it causes such activation. The results suggest that the difference in
      coupling to adenylate cyclase is likely at least partially due to a difference in
      coupling to an adenylate cyclase subtype whose activation is regulated by PKC.
      Therefore, the possible growth effects mediated by this receptor in different
      embryonic or tumoral cells through activation of adenylate cyclase are not likely
      to be an important intracellular pathway for these effects in normal tissues.

PMID- 9194578
TI  - Overexpression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in human
      cutaneous malignant melanoma.
AB  - p21(WAF1/CIP1) (p21) is an inhibitor of cyclin-dependent kinases recently
      identified as the downstream effector of wild-type p53-mediated cell cycle
      arrest. The gene coding for p21 may function as a negative regulator of melanoma
      growth, progression, and metastasis. Using immunohistochemistry and Western
      blotting, we investigated the expression of p21 in human melanocytic
      proliferations. Immunohistochemical staining was performed on 13 common acquired
      nevi, 12 dysplastic nevi, 23 primary malignant melanomas, and 12 metastatic
      melanomas. Common acquired nevi showed minimal p21 staining (1.8+/-0.3%, mean+/
      SEM). The percentage of positive nuclei was slightly elevated in dysplastic nevi
      (8.9+/-1.7%). Both primary malignant melanoma (29+/-3%) and metastatic melanoma
      (33+/-5%) demonstrated a significantly increased number of p21-positive nuclei
      compared to benign lesions (p<0.001). p21 was strongly expressed even in actively
      proliferating lesions as confirmed by MIB-1 labelling, and although the majority
      of p21-positive cells likely represent a non-proliferating population, staining
      was occasionally observed in cells undergoing mitosis, suggesting abnormal
      function of this cell cycle inhibitor in malignant melanoma. Overexpression of
      p21 in metastatic melanoma compared to common acquired nevi was confirmed by
      Western blot analysis of human tumor samples. These findings suggest that
      increased p21 expression relative to benign nevi is not sufficient to control
      melanoma growth in vivo.

PMID- 9194579
TI  - Quantification of vascularity in nodular melanoma and Spitz's nevus.
AB  - Spitz's nevi are acquired benign melanocytic skin tumors. Usually they are
      differentiated from nodular melanoma by clinical and histopathological criteria.
      Since Spitz's nevi are one of the most common simulators of nodular melanomas
      their bizarre histopathology may cause diagnostic confusion and make it difficult
      to differentiate these two melanocytic tumors. One of the histologic features
      shared by Spitz's nevus and nodular melanoma is prominent vascularity. The
      ability of malignant melanoma to induce angiogenesis is well established whereas
      benign melanocytic tumors do not have a prominent overall vascularity. The
      purpose of this study was to find out whether the degree of vascularity of
      nodular melanomas differs significantly from that of benign Spitz's nevi. In this
      study the number of microvessels and the vessel area were determined in 23
      Spitz's nevi and 16 nodular melanomas. The number of microvessels and the vessel
      area were determined on Ulex Europaeus agglutinin I-stained sections by computer
      assisted image analysis. Two methods of measurement were used, namely systematic
      and selective sampling. Measurement of the whole tumor specimen (systematic
      sampling) revealed a vessel count of 10.83/field (SD +/-5.97) for Spitz's nevi
      whereas nodular melanomas exhibited a significantly lower (p=0.04) vessel count
      of 6.44/field (SD +/-3.85). This difference was even more pronounced when the
      vessel area (Spitz's nevi: 17.85x10-4mm2, SD +/-10.32; nodular melanomas: 7.88x10
      4mm2, SD +/-5.23) was investigated (p < 0.001). The difference in vessel area and
      vessel count was insignificant for areas exhibiting the greatest vascularity
      (selective sampling). Measurement of vessel count and vessel area lead us to
      conclude that Spitz's nevi have a significantly higher vascularity than do
      nodular melanomas. Our results thus indicate that angiogenesis in these pigmented
      lesions is not correlated with malignancy.

PMID- 9194580
TI  - Adhesion molecule expression in normal skin and melanocytic lesions. Role of UV
      irradiation and architectural characteristics in nevi.
AB  - Cell adhesion between surfaces of cells and to extracellular matrices represents
      a fundamental mechanism in tissue organization and influences the biological
      behaviour and the architecture of tumors. We investigated the expression of
      various adhesion molecules in normal skin (n=5), nevi (n=29), and malignant
      melanoma (n=10) by immunohistochemistry. Special attention was paid to the
      correlation between adhesion molecule expression and the respective architectural
      features, e.g. UV-induced morphological changes, and the arrangement of
      melanocytes in congenital nevi. In nevi, a single erythemagenic dose of UV-light
      did not influence the integrin expression of melanocytes, but results in an
      upregulation of alpha3 beta1- and alpha6 beta1-integrin within the suprabasal
      layers of the epidermis. This suprabasal labelling was associated with an
      increased number of suprabasal melanocytes in UV-irradiated nevi which were
      detected with HMB-45 antibody. Nine of 10 congenital nevi demonstrated a
      labelling of alpha4 beta1-integrin only in melanocytes of the deeper dermis. This
      integrin previously has been associated with high tumor thickness and the
      clinical outcome in melanomas. The integrin profile observed in melanomas
      differed in part from that seen in nevi with expression of beta2- and beta3
      integrins in some cases. The results may indicate a correlation between adhesion
      molecule expression and histopathological findings in melanocytic lesions.

PMID- 9194581
TI  - Cutaneous histopathology of Sezary syndrome: a study of 41 cases with a proven
      circulating T-cell clone.
AB  - Sezary syndrome is an uncommon variant of cutaneous T-cell lymphoma (CTCL)
      characterized by erythroderma, pruritus, adenopathy, and circulating atypical T
      lymphocytes with cerebriform nuclei. The definition of Sezary syndrome can be
      further refined by including only patients with a circulating peripheral blood
      population of clonal T-cells. We have evaluated 79 skin biopsies from such a
      group of 41 erythrodermic patients with circulating Sezary cells and a clonal
      population of T-cells detected by T-cell receptor-beta gene rearrangement on
      Southern analysis of peripheral blood mononuclear cells. Histopathologic features
      consistent with chronic dermatitis were observed in 26/79 (33%) skin biopsy
      specimens, emphasizing that a non-specific histologic appearance is common.
      Evidence of CTCL was lacking in 11/41 patients on biopsy of their erythrodermic
      skin. The survival of these patients was not significantly different from 30/41
      patients in whom skin biopsies revealed changes diagnostic of CTCL, such as a
      dermal lymphocytic band with atypical lymphocytes (18/79, 23%) or a mycosis
      fungoides-like infiltrate (30/79, 38%). This study confirms that non-specific
      cutaneous histopathologic findings are common in Sezary syndrome, even when a
      circulating T-cell clone is present. This stresses the need for peripheral blood
      genetic analysis and for multiple or repeat skin biopsies in erythrodermic
      patients when there is high clinical suspicion of CTCL.

PMID- 9194582
TI  - Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and
      Sezary syndrome: a critical reappraisal.
AB  - It is often difficult to make a clinical or histologic diagnosis of erythrodermic
      mycosis fungoides (MF) and Sezary syndrome (SS). Whereas the histologic
      parameters for making a diagnosis of MF with well-developed patch and plaque
      stage lesions are clearly defined, the same criteria appear to be less relevant
      for diagnosing MF in patients with erythroderma secondary to the disease. In
      order to better define the histologic features of erythrodermic MF and SS, we
      studied 28 routine histologic sections of 17 patients with known erythrodermic MF
      or SS. Sections were reviewed independently by 2 dermatopathologists. Each of 24
      parameters was scored semi-quantitatively and the data were compared to data
      previously reported from a group of 64 patients with limited patch and plaque
      stage lesions of MF. When compared to biopsies from patients with limited
      patch/plaque lesions, biopsies taken from erythrodermic patients displayed more
      parakeratosis (p=0.0492) and acanthosis (p=0.0046), less disproportionate
      epidermotropism, fewer lymphocytes aligned within the basal layer (p=0.0045),
      fewer hyperconvoluted cells in the epidermis, more dermal hyperconvoluted cells
      (p=0.0191), more papillary dermal fibrosis (p=0.0002), more prominent
      teleangiectasias (p=0.0028) and more mitotic figures. The histologic features of
      erythrodermic MF and Sezary syndrome are even more subtle than the features of
      patch and plaque stage MF, thus rendering the histologic diagnosis more
      difficult.

PMID- 9194583
TI  - Search for Kaposi's sarcoma-associated virus DNA in hemangioproliferative
      disorders and cutaneous malignant lymphoma.
AB  - Recently, a Kaposi's sarcoma-associated herpesvirus (KSHV) was discovered. We
      evaluated by PCR 14 paraffin-embedded specimens with the histological diagnosis
      of endemic, classic and HIV-associated Kaposi's sarcoma (KS) for the presence of
      the KSHV DNA sequence. In addition, biopsies of adjacent, histologically
      unaffected skin, peripheral-blood mononuclear cells (PBMCs) of HIV-infected KS
      patients, PBMCs of one classic KS patient, and specimens of patients with
      hemangioproliferative disorders other than KS as well as samples of cutaneous T-
      and B-cell lymphoma were analyzed for KSHV. In all cases of KS, independent of
      the KS subtype, KSHV was detected in lesional skin. No KSHV was found in biopsies
      of the adjacent unaffected skin or PBMCs of HIV-infected KS patients. We found
      KSHV in the PBMCs of a patient with classical KS. All specimens of cutaneous T-
      and B-cell lymphomas or lymphomatoid papulosis were negative for KSHV. In
      addition, the samples with hemangioproliferative disorders other than KS were
      negative for KSHV. There was one borderline case of KS or acroangiodermatitis
      that was positive for KSHV. Additional histological sections and clinical
      evaluation confirmed the diagnosis of classic KS. In summary, the data indicate
      that PCR for KSHV should be a useful diagnostic tool in cases of
      hemangioproliferative disorders.

PMID- 9194584
TI  - Less expression of cyclin E in cutaneous squamous cell carcinomas than in benign
      and premalignant keratinocytic lesions.
AB  - In a previous study, we showed that overexpression of cyclin D, a G1 cyclin, is
      frequently associated with keratinocyte carcinogenesis as an early event. Another
      G1 cyclin, cyclin E, was recently suggested to be a prognostic marker for breast
      cancer. In order to evaluate the role of cyclin E in human keratinocyte
      carcinogenesis, we analysed the expression of cyclin E by immunohistochemistry in
      normal skin, seborrheic keratosis (SK), keratoacanthoma (KA), actinic keratosis
      (AK), Bowen's disease (BD), basal cell carcinoma (BCC) and squamous cell
      carcinoma (SCC). Positive cells were seen rarely in normal epidermis, in 9 of 20
      cases of SK, in 5 of 6 cases of KA, in 9 of 13 cases of AK and in all 27 cases of
      BD. Some of the cases of AK and BD had positive cells in the superficial
      epidermis, where atypicality is less obvious. In contrast, positive cells were
      seen in 4 of 25 cases of SCC and none of 15 cases of BCC. These results suggest
      that expression of cyclin E plays a role in the formation of benign and
      premalignant keratinocytic tumors, whereas down-regulation of cyclin E expression
      may be involved in carcinogenesis in human keratinocytes.

PMID- 9194585
TI  - An immunohistochemical analysis of radiation fibroblasts.
AB  - A commonly recognized feature of chronic radiation dermatitis is the presence of
      mesenchymal cells with large atypical nuclei known as radiation fibroblasts.
      Little is known about their lineage or potential for neoplastic transformation.
      To investigate these properties, we examined 16 biopsy specimens in which
      radiation fibroblasts were present with antisera to mesenchymal determinants
      (FXIIIa, CD34, HHF-35), a proliferation marker (Ki-67), and a tumor-suppressor
      protein that is overexpressed in many cancers (p53). Radiation fibroblasts were
      largely negative for the markers of lineage that we employed - only 2 of 16
      specimens showed strong expression of FXIIIa, with weak expression in another
      case. Scattered radiation fibroblasts expressed CD34 in one case. HHF-35 (muscle
      specific actin) stained small, dendritic cells in the superficial dermis, but not
      radiation fibroblasts. P53 was not detected within radiation fibroblasts in any
      of our cases, but was overexpressed by endothelial cells in 2 cases. Ki-67
      stained rare endothelial and interstitial cells but not radiation fibroblasts.
      Radiation fibroblasts are immunophenotypically distinct from dermal dendrocytes
      and myofibroblasts. They appear to be non-cycling cells, and do not express high
      levels of p53 despite their marked nuclear atypia. Their phenotype argues against
      their possible role as progenitors of atypical fibroxanthoma (AFX) and
      dermatofibrosarcoma protuberans (DFSP) which are associated with ionizing
      radiation-induced skin damage.

PMID- 9194586
TI  - Identification of aneuploidy in recurrent clear cell hidradenoma by DNA image
      cytometry (ICM-DNA).
AB  - Since malignant clear cell hidradenoma (CCH) is often characterized by only
      slight and sometimes by absent nuclear anaplasia, even in metastases, definitive
      differentiation from its benign counterpart by light microscopy may be very
      difficult. Herein, we report the case of a 72-year-old woman suffering from a CCH
      on the back, which showed local recurrence following incomplete excision. By
      light microscopy no unequivocal signs of malignancy were found either in the
      primary or the recurrent tumor. However, unusual deep extension to the subcutis
      with some architectural disorder was seen in the latter. Identification of
      prospective malignancy in such cases of borderline histopathological features is
      one of the main indications for diagnostic DNA image cytometry (ICM-DNA).
      Application of this method to enzymatic cell separation specimens of the
      recurrence detected marked DNA-aneuploidy with a stemline ploidy of 2.60 c and
      single events up to 6.7 c, whereas a nearly exact diploid DNA-stemline was found
      in the primary. We suppose from our results that a prospective malignant CCH with
      aneuploid DNA-stemline has developed out of its DNA-diploid counterpart. The need
      for total surgical removal of apparently benign clear cell hidradenomas is
      further stressed by this observation. Criteria for the diagnosis of malignancy in
      CCH are reviewed.

PMID- 9194587
TI  - Smooth-muscle hamartoma of the tunica dartos of the scrotum: report of a case.
AB  - Hamartomatous proliferations of genital smooth muscle are uncommon and may be
      easily overlooked if the normal microscopic appearance of the scrotal dartos is
      unfamiliar to the pathologist. We describe a hamartomatous proliferation of the
      scrotum in a 60-year-old patient in which incomplete knowledge of the regional
      histology caused initial problems in diagnosis. On histologic examination, the
      lesion consisted of an expansile, unencapsulated, relatively circumscribed
      proliferation of smooth muscle accompanied by muscular arterioles and prominent
      nerve branches embedded in a densely collagenized stroma. These features are
      dissimilar both clinically and histologically from all previous reported lesions
      at this site. We highlight the histologic differences between our case and
      genital leiomyomas, and the spectrum of hamartomatous smooth-muscle
      proliferations associated with a Becker nevus, and congenital and acquired smooth
      muscle hamartomas.

PMID- 9194588
TI  - Effects of local changes in the helix flexibility on electrophoretic migration of
      DNA in agarose gel.
AB  - We present a study of how kinks, flexible bends, and flexible joints in the DNA
      helix, induced by binding cis-diamminedichloroplatinum(II) (cis-DDP),
      transdiamminedichloroplatinum(II) (trans-DDP), and
      chlorodiethylenetriammineplatinum(II) (dien-Pt) to the DNA, affect the
      electrophoretic migration of DNA in agarose gels. For long DNA the conformation
      oscillates between extended and compact states during the migration, as for
      native DNA. The presence of flexible joints decreases both the length of time and
      the step length of the cycles, but in a compensatory manner so that there is no
      net effect on the mobility. This demonstrates that in some cases mobility alone
      cannot detect pertubations in the DNA helix. Kinks and flexible bends reduce the
      mobility because they both lead to longer time periods of the cycles. With kinks
      the reduction is strongest at low fields because at high fields the kinks are
      straightened out; the steps thus become even longer than for native DNA. The
      results suggest that a combination of mobility and orientation measurements on
      reptating DNA can be used for distinguishing different kinds of structural
      alterations in the DNA.

PMID- 9194589
TI  - Length and sequence variation in D7S22 (g3) alleles studied by high resolution
      length measurements and nucleotide sequencing.
AB  - In a study of DNA sequence and length variation in the repeat array of small
      D7S22 alleles, 100 alleles typed as the common 14 repeat allele (14R) and 92 rare
      ones were selected for further characterization. A polymerase chain reaction
      (PCR) based allele length measurement method revealed a discontinuous
      distribution of alleles. The 92 rare alleles were grouped by their number of
      repeats. All, except four 6R alleles were distributed within the 11R-19R allele
      groups. The 14Rs revealed no further length variation while 7 out of the 92 rare
      alleles showed small length deviations from the other alleles within their
      respective groups. Nucleotide sequencing of the repeat array was performed in 17
      alleles selected from each of the nine allele groups. The micro length variation
      within allele groups was caused by the presence of either 33, 36 or 37 bp repeats
      in given positions. A comparison of three 14Rs revealed no further sequence
      variation between these. Nine out of the fourteen repeats in the 14R differed in
      sequence and/or size. Based on this difference the repeat array sequence was
      converted into a code of different variant repeats. The 6R showed a variant
      repeat code quite unlike that of the 14R, while the encoded allele structure of
      the other rare alleles suggested that most of them may have evolved from a 14R
      allele by deletion or duplication of repeat units. Nucleotide sequencing of
      progenitor and mutant in a D7S22 de novo mutation as well as typing in a
      polymorphic site near the repeat array suggested that the event was an intra
      allelic deletion of exactly three repeats. The present findings indicate that the
      14R is ancestral to most rare small alleles, and that mutations in small alleles
      most often are intra-allelic events leading to a change in bp size equal to an
      integer number of repeats.

PMID- 9194590
TI  - Detection of somatic mutations in the mitochondrial DNA control region of
      colorectal and gastric tumors by heteroduplex and single-strand conformation
      analysis.
AB  - Each entire hypervariable region of the mitochondrial DNA control region was
      screened for mutations from paired normal and tumor DNA corresponding to a group
      of 21 patients (13 colorectal and 8 gastric adenocarcinomas) using both
      heteroduplex analysis and single-strand conformation analysis. These two mutation
      scanning strategies allowed the identification of sequence alterations in 3/13
      (23%) colorectal tumors and in 3/8 (37%) gastric tumors. Heteroduplex analysis
      showed the heteroplasmic state of the majority of these tumor mutations. Sequence
      analysis revealed two A:T/G:C transitions (nucleotide positions: 16241 and 16166)
      in hypervariable region 1 (HV1) and two C:G/T:A transitions (nucleotide
      positions: 76 and 312), one A:T/G:C transition (nucleotide position: 93), a 1
      basepair C:G deletion (nucleotide position: 309), and a 2-base-pair CC:GG
      insertion (nucleotide position: 309) in the HV 2 region. A considerable
      proportion of these mutations was found in homopolymeric regions which are highly
      polymorphic among humans. Different mechanisms (clonal expansion, increased
      oxidative damage, and nuclear mutator mutations) were suggested to explain the
      increased mitochondrial DNA mutation rate observed in cancer.

PMID- 9194591
TI  - Mutational analysis of the genes encoding urokinase-type plasminogen activator
      (uPA) and its inhibitor PAI-1 in advanced ovarian cancer.
AB  - Evidence has accumulated that urokinase-type plasminogen activator (uPA), its
      inhibitor (PAI-1) and receptor (uPAR) are involved in tumor invasion and
      metastasis. We analyzed the DNA sequences encoding these factors to see if they
      are altered in the ovarian cancer cell lines OV-MZ-6, OV-MZ-19, and OVCAR-3. In
      the uPA-encoding cDNA derived from OV-MZ-6 cells (but not in the uPA-cDNA from
      OVCAR-3 and OV-MZ-19), a so-far unknown mutation was identified in codon 121,
      resulting in a proline to leucine exchange. This exchange creates an AluI
      restriction site making restriction fragment length polymorphism (RFLP) analyses
      possible. Previously published PAI-1 sequences pointed to a variation of amino
      acid 15 of the PAI-1 signal sequence representing either threonine or alanine,
      which was confirmed in the present study. The uPAR cDNAs of all three cell lines
      encoded the published wild-type sequence. In order to elucidate the possible role
      of the Pro121Leu exchange in uPA and the Ala/Thr variants in the signal sequence
      of PAI-1 in the development and/or progression of human ovarian cancer, we
      studied the presence of these mutants or variants in a series of 22 ovarian
      cancer tissues. In addition to the wild-type sequence, the Pro121Leu exchange in
      the uPA sequence was detected in 10 out of 22 tumor tissues; 11 tumors carried
      exclusively the Pro121 allele; in one case exclusively the Leu121 allele was
      detected. In 18/22 tumors, triplet 15 in the signal sequence of PAI-1 encoded
      alanine, four DNAs contained both the Ala and the Thr allele. Furthermore, we
      analyzed another known common single-base-pair insertion/deletion polymorphism
      (ins/del allele) found in the promoter region of the PAI-1 gene and thought to be
      of functional importance in regulating PAI-1 gene expression. The PAI-1 ins
      allele was found in 3/22, the del-allele in 6/22 and both alleles in 13/22
      ovarian cancer tissues. In genomic DNA isolated from peripheral blood of 23
      healthy donors, we observed similar allele frequencies of the three polymorphisms
      as found in the 22 ovarian carcinomas. Taken together, these results suggest that
      the polymorphisms observed in the uPA and PAI-1 genes may not be linked to
      ovarian cancer.

PMID- 9194592
TI  - Five cases of forensic short tandem repeat DNA typing.
AB  - In medicolegal samples DNA is often broken into fragments. In many cases, only
      the amplification of short tandem repeated DNA stretches (STRs), which are
      located in noncoding regions, allows DNA typing of such degraded materials. To
      demonstrate the high diversity of biological materials which forensic biologists
      have to deal with, and to outline the success rates and limits of the method, we
      describe five cases (minute amount of tissue on barrel, tissue in decay, tumor
      tissue, sperm after multiple rape, stored urine samples) in which forensic DNA
      typing was successfully performed by use of the short tandem repeats HUMDHFRP2,
      HUMD8S306, HUMCD4, HUMF13A1, HUMTH01, HUMVWA, and HUMFES.

PMID- 9194593
TI  - Structural transitions of human serum albumin: an investigation using
      electrophoretic techniques.
AB  - The influence of pH and urea concentration on the electrophoretic mobility of
      native and reduced human serum albumin was evaluated by zonal electrophoresis
      across transverse urea gradients as well as by migration across transverse pH
      gradients in gels containing varying concentrations of urea. Exposure to urea
      results in a change of both pI and hydrodynamic volume of the albumin molecule.
      At acidic pH, the former effect is brought about by lower urea concentrations
      than the latter, as made evident by a biphasic denaturation curve; in alkaline
      buffers, all structural transitions occur at once, and a typical sigmoidal curve
      is observed. Below pH 6, the lower the pH, the lower the urea concentration
      causing albumin denaturation. For instance, in the presence of 3 M urea, below pH
      5 > 95% of the protein is present in its denatured state, above pH 8 > 90% is in
      its native form, whereas in the 6.5-7.5 pH range the two components have similar
      abundance. Also, the reversibility of the transition between folding and
      unfolding depends upon pH, and is complete only above pH 6. After inclusion of
      beta-mercaptoethanol in the albumin sample the urea concentration required to
      bring about protein unfolding increases between pH 4 and 6 and decreases
      thereafter.

PMID- 9194594
TI  - Combined immunostaining and Coomassie Brilliant Blue staining of polyvinylidene
      difluoride membranes without organic solvent.
AB  - A method for staining proteins on polyvinylidene difluoride membranes without
      using organic solvent is described. The method uses preblocking of the membrane
      with either Tween 20 or polyethylene glycol followed by staining with 0.01%
      Coomassie Brilliant Blue. No destaining of the membrane is needed afterwards.
      Preblocking with polyethylene glycol is compatible with microsequencing while
      Tween 20 leads to very low initial yields. Preblocking with Tween 20 has the
      additional advantage of allowing immunostaining followed by Coomassie Brilliant
      Blue staining for total protein on the same membrane.

PMID- 9194595
TI  - Quantitative description of analyte migration behavior based on dynamic
      complexation in capillary electrophoresis with one or more additives.
AB  - A comprehensive theory is proposed to describe the migration behavior of analytes
      in capillary electrophoresis (CE) when one or more additives are present in the
      buffer solution. This theory amalgamates and extends the previous work done by
      others. The capacity factor (k') in this theory is defined as the product of the
      equilibrium constant and the additive concentration, thus, k' changes linearly
      with additive concentration. The net electrophoretic mobility of an analyte is a
      function of k', therefore, it can be changed by varying the additive
      concentration. Three parameters are needed to predict the mobility of an analyte
      in a one-additive CE system: the mobility of the free analyte, the mobility of
      the complex, and the equilibrium constant for the analyte-additive interaction
      (which determines the fraction of the free analyte at different additive
      concentrations). When additives are used, the change in viscosity obscures this
      relationship, therefore, a viscosity correction factor is required to convert all
      mobilities to an ideal state where the viscosity remains constant. The migration
      behavior of an analyte in a solution with multiple additives can be predicted and
      controlled, once the equilibrium constants of the interactions between the
      analyte and each of the additives are obtained separately. beta-Cyclodextrin and
      hydroxypropyl-beta-cyclodextrin are used as additives and the migration behavior
      of phenol, p-nitrophenol, and benzoic acid are studied as a model system to
      verify this theory. When the necessary viscosity correction factor is included,
      the net electrophoretic mobilities of the analytes obtained from experimental
      results agree with the values predicted by the theory based on dynamic
      complexation. Although only experiments with one and two additives were carried
      out to verify the theory, the equations apply to situations when more than two
      additives are used. The relationship between the theories of electrophoresis and
      chromatography is clarified.

PMID- 9194596
TI  - Capillary zone electrophoresis of oligonucleotides in isoelectric buffers and
      against a stationary pH gradient.
AB  - Capillary zone electrophoresis of oligonucleotides in a background electrolyte of
      two different types of stationary buffers is proposed: single, isoelectric
      amphoteres and focused carrier ampholytes. In the first case, two zwitterionic
      molecules are evaluated: lysine and histidine. Although the former has a five
      times higher buffering power (beta) at the pI (9.74) than the latter (pI 7.47),
      due to the favorable delta pK value (1.6 vs. 3) and thus should be the preferred
      species, a new parameter for evaluating the performance of isoelectric buffers is
      proposed: the beta/lambda ratio, i.e., the ratio between the buffering power and
      its conductivity. Ideal buffers are those with the highest beta/lambda ratio,
      since this allows delivering very high voltage gradients with minimal Joule
      effects. Since the pI of Lys is situated in a pH region (9.74) where bulk water
      begins to conduct, whereas His has a pI close to neutrality, the beta/lambda
      ratio is more favorable for His than for Lys. In the second case (zone
      electrophoresis of oligonucleotides against a preformed pH gradient), it is shown
      that migration against a pH 6.5-10 Pharmalyte carrier ampholyte pH gradient
      offers a unique analyte resolution. This is possibly due to two effects: (i) When
      injected at the alkaline extreme (ca. pH 10) of the pH gradient, the
      oligonucleotide zones undergo a stacking effect, with consequent zone sharpening,
      due to modulation of their free mobility via protonation of the -OH group
      (enolate ion) in the hetero aromatic rings of G and T, which undergo a lactam
      lactim transition. (ii) As the zones migrate down the pH gradient, they transit
      through a pH 6.5-8.5 zone where, for Pharmalytes, the beta/lambda ratio reaches a
      maximum and is constant as well. This last condition allows high voltage
      gradients (typically 1000 V/cm, even in 75 microm capillaries) to be delivered,
      thus greatly reducing the analysis time and maintaining peak sharpness, due to
      limited diffusion.

PMID- 9194597
TI  - Temperature-programmed capillary electrophoresis for the analysis of high-melting
      point mutants in thalassemias.
AB  - The behavior of different sieving polymers for unambiguous determination of point
      mutations in genomic DNA, based on electrophoresis in thin capillaries, is
      evaluated. High melters from thalassemia patients are separated by exploiting the
      principle of denaturing gradient gel electrophoresis, in fact, of its variant
      utilizing temperature gradients (TGGE), along the migration path, encompassing
      the melting points of both homo- and heteroduplex, polymerase chain reaction
      (PCR)-amplified DNA fragments. Unlike TGGE, where the temperature gradient exists
      along the separation space, the denaturing temperature gradient in the fused
      silica capillaries is time-programmed, so as to reach the Tm's of all species
      under analysis prior to electrophoretic transport past the detector window. The
      DNA fragments are injected in a capillary maintained (by combined chemical and
      thermal means) just below the expected Tm values. The deltaT applied is rather
      minute (1-1.5 degrees C) and the temperature gradient quite shallow (e.g., 0.05
      degrees C/min). The denaturing thermal gradient is generated internally, via
      Joule heat produced by voltage ramps. This method is applied to the analysis of
      the most common point mutations in thalassemias, characterized by being high
      melters (in the temperature range of 60-62 degrees C) in presence of 6 M urea.
      Point mutants are fully resolved into a spectrum of four bands only when poly(N
      acryloylaminopropanol) and hydroxyethylcellulose are used. However, the former
      offers the best separation capability at such high temperatures.

PMID- 9194598
TI  - Effect of zwitterionic surfactants on the separation of proteins by capillary
      electrophoresis.
AB  - The effect of zwitterionic surfactants on capillary electrophoretic separation of
      proteins was investigated using an uncoated silica capillary column and different
      buffers containing zwitterionic surfactants. The effects of N-alkyl-N,N-dimethyl
      ammonio-1-propane-sulfonates on the electrophoretic mobility of three different
      proteins, namely albumin, lysozyme and myoglobin, were examined. The addition of
      N-alkyl-N,N-dimethylammonio-1-propane sulfonate in phosphate saline buffer is
      important in minimizing protein-capillary wall interactions, and facilitated an
      efficient electrophoretic mobility of myoglobin and lysozyme. The separation
      efficiency of proteins also depends on the injection pressure for the control of
      migration time and the peak sharpness. The electrophoretic conditions were
      applied to evaluate the separation of lysozyme, myoglobin and albumin. The
      zwitterion surfactants can form a dynamic coating on the capillary surface,
      thereby reducing the number of adsorption sites to which proteins may adsorb.

PMID- 9194599
TI  - Capillary electrophoretic separation of tricyclic antidepressants using charged
      carboxymethyl-beta-cyclodextrin as a buffer additive.
AB  - Charged carboxymethyl-beta-cyclodextrin was successful in the capillary
      electrophoretic separation of a series of tricyclic antidepressants. The
      cyclodextrin alone was successful in the separation of carbamazepine,
      protriptyline, desipramine, clomipramine, and opipramol using a 3
      (trimethoxysilyl)propyl methacrylate capillary coating to reduce the
      electroosmotic flow. The ideal buffer pH was found to be in the range of 6-7 and
      the ideal cyclodextrin concentration to be 10 mM. All nine antidepressants were
      resolved using the charged cyclodextrin in the micellar electrokinetic
      chromatography (MEKC) mode with sodium dodecyl sulfate as the surfactant. Neither
      the cyclodextrin nor the surfactant alone were successful in resolving the whole
      series of compounds under investigation but a combination of both produced the
      separation. Separations were performed on a linear polyacrylamide coated
      capillary. The ideal pH of the buffer was in the range of 5-7.

PMID- 9194600
TI  - Capillary electrophoresis of glycosaminoglycan-derived disaccharides: application
      to stability studies of glycosaminoglycan chitosan complexes.
AB  - Capillary zone electrophoresis (CZE) was used to separate the disaccharides
      produced by chondroitinase digestion of chondroitin sulfates. The main
      disaccharides formed upon depolymerization have identical charge and mass.
      Baseline resolution of these two compounds was achieved by selecting appropriate
      concentration and pH of a borate buffer. Validation of the method showed a good
      linearity of the response and a very satisfactory reproducibility of migration
      times with a relative standard deviation (RSD) of less than 0.4%. The
      reproducibility of peak areas was improved by using an internal standardization.
      The addition of cinnamic acid (internal standard) to the incubation medium
      allowed us to perform kinetic measurements of the depolymerization while keeping
      a baseline resolution of the two main disaccharides analyzed during the complete
      digestion course even when their concentration in the incubation medium
      increased. Application of this method to the comparison of the rate of hydrolysis
      of chondroitin sulfate and of a complex associating chondroitin sulfate with
      chitosan showed clearly that, at the physiological pH, chitosan protected the
      chondroitin sulfate from depolymerization. This phenomenon was more pronounced as
      the pH of the incubation medium was far from the optimum pH activity of the
      chondroitinase.

PMID- 9194601
TI  - Sample matrix effects on glycopeptide stability by high performance capillary
      electrophoresis.
AB  - High performance capillary electrophoresis (CE) of glycoprotein digests
      frequently reveals extensive microheterogeneity associated with specific protein
      glycosylation sites. The choice of the sample matrix can influence the
      electrophoretic migration time, peak shape and resolution, as well as the
      physical stability of the product glycopeptides. Acetic acid is a frequently
      employed sample matrix for both capillary electrophoresis and electrospray
      ionization-mass spectrometry (ESI-MS). Acetic acid appears to enhance the
      spontaneous hydrolysis of sialic acids from the nonreducing termini of
      glycopeptides in a time- and concentration-dependent manner, even at 5 degrees C,
      as evidenced by changes in the electrophoretic mobility and ESI-MS spectra of the
      resulting glycopeptides. The observed parallel electrophoretic mobility changes
      for specific glycoforms are consistent with the induction of peptide structure
      with time. Asialoglycopeptide mobilities were stable in acetic acid.
      Electrophoretic mobilities can be stabilized with propionic acid sample matrix
      with no apparent structural changes observed by ESI-MS within 31 h. Migration
      time reproducibility was in the range of 0.1% relative standard deviation (N = 7)
      with excellent peak shapes and enhanced glycopeptide resolution.

PMID- 9194602
TI  - Prothymosin alpha: efficient sequence determination by experimental and
      theoretical capillary electrophoretic support.
AB  - A rapid and efficient primary structure elucidation of prothymosin (ProT alpha)
      and its enzymatic fragments was performed by a combination of matrix-assisted
      laser desorption ionization mass spectrometry (MALDI), automatic N-terminal Edman
      degradation, and the available theoretical predictions of electrophoretic
      mobility in capillary electrophoresis (CE) as a basis suggesting active sites of
      ProT alpha in the different bioassays.

PMID- 9194603
TI  - Characterization of thioredoxins by sodium dodecyl sulfate-slab gel
      electrophoresis and high performance capillary electrophoresis.
AB  - Disulfide containing proteins--thioredoxins from E. coli and pig heart
      mitochondria--were characterized by sodium dodecyl sulfate (SDS)-electrophoresis
      and high performance capillary electrophoresis (HPCE). Following the
      mitochondrial thioredoxin samples at different stages of purification, we found
      that their electrophoretic patterns vary, dependent on the redox condition of
      isolation, preparation of the samples for SDS-electrophoresis, and sample
      storage. All these factors influenced the relative intensities of several protein
      bands with thioredoxin-like mobility, whereas the sample storage also resulted in
      the appearance of SDS- and dithiothreitol (DTT)-resistant high molecular mass
      forms, probably thioredoxin dimers. The multiple forms of the thioredoxin from
      pig heart mitochondria in SDS-electrophoresis might be dependent on the oxidation
      state of the protein cysteine residues. A commercial preparation of the
      thioredoxin from E. coli did not exhibit any changes in mobility in SDS gels
      whether the sample was prepared with or without DTT. After the final purification
      step no correlation was found between mitochondrial thioredoxin activity,
      determined in the insulin assay, and its purity in SDS-electrophoresis. A
      correlation was, however, found when analyzing the thioredoxin by HPCE. The
      latter approach demonstrated the heterogeneity of the thioredoxin samples
      homogeneous on SDS electrophoresis, only one of the several HPCE peaks being
      active in the insulin assay. Also, thioredoxin from E. coli, homogeneous on SDS
      electrophoresis, was found heterogeneous on HPCE. The peak corresponding to the
      insulin-dependent thioredoxin activity was split into two by DTT treatment,
      suggesting that redox transformations of thioredoxin could be followed by HPCE.

PMID- 9194604
TI  - Density gradient isoelectric focusing of proteins in artificial pH gradients made
      up of binary mixtures of amphoteric buffers.
AB  - A density gradient electrophoresis apparatus made of Perspex (7 cm, O 2.2 cm)
      with a circular platinum anode and a palladium cathode was used for the
      separation of proteins in free liquid. Following a concept developed by M. Bier
      et al. (Electrophoresis 1993, 14, 1011-1018), mixtures of two suitable amphoteric
      buffers I and II provide for media with a fixed and electrophoretically stable pH
      or were used for the generation of preformed (electrophoretically stable) pH
      gradients covering about 1 pH unit. Amphoters I and II are considered suitable if
      there is overlap between (pK(1,1)-1-2) and the pK(2,II)+1+2) region. 3-(N
      Morpholino)propanesulfonic acid (MOPS) and gamma-amino-n-butyric acid (GABA) were
      used as an example. Two approaches were followed: (i) rate-zonal separation of
      test proteins in a pH window, formed by a fixed ratio of MOPS/GABA. (ii)
      Isoelectric focusing in a shallow preformed pH gradient, made up of inverse
      reciprocal linear gradients of MOPS and GABA. At isopH, test proteins (bovine
      serum albumin, cytochrome c, ferritin, hemoglobin, lactoglobulin, myoglobin, and
      transferrin) were rate-zonally separated within a short time. Even the separation
      of the A and B forms of lactoglobulin was feasible at isopH. The glycoforms of
      transferrin were separated and enriched on a pH 5.2-6.1 pH gradient, indicating
      that pH differences of about 0.01 still permit resolution. Contrary to the ill
      defined Ampholines, the cost of these well-defined amphoters is low.

PMID- 9194605
TI  - Isolation of rat hepatic peroxisomes by means of immune free flow
      electrophoresis.
AB  - Rat hepatic peroxisomes (PO) were separated from other cell organelles by free
      flow electrophoresis (FFE) in combination with immunocomplexing PO prior to FFE
      with an antibody directed against the cytoplasmic aspect of the peroxisomal
      membrane protein PMP 70. This novel approach is based on a method termed antigen
      specific electrophoretic cell separation (ASECS) which was originally introduced
      for the isolation of human T and B lymphocyte subpopulations by Hansen and Hannig
      (J. Immunol. Methods 1982, 51, 197-208). We adapted this technique to PO
      isolation from a crude peroxisomal fraction, streamlining it by the following
      modifications: (i) The sandwich-technique recommended to further lower a negative
      surface charge was renounced. (ii) Instead, the pH of the electrophoresis buffer
      was raised from 7.2 to 8.0, thus minimizing the electrophoretic mobility of the
      particles immunocomplexed due to the fact that the isoelectric point (pI) of IgG
      molecules is close to pH 8.0. PO isolated by this modification, referred to as
      immune free flow electrophoresis (IFFE), are as pure, intact, and structurally
      well-preserved as are highly purified PO obtained by density gradient
      centrifugation. The technique is currently applied for the isolation of
      peroxisomal subpopulations that are difficult to obtain by means of density
      gradient centrifugation.

PMID- 9194606
TI  - Isolation of subcellular-sized particles separated by electrophoresis in dilute
      polymer solution, using commercial electrophoresis apparatus with intermittent
      scanning of fluorescence.
AB  - Resolution of subcellular-sized particles in electrophoresis employing semi
      dilute polymer solutions as "sieving media" improves as the polymer concentration
      is decreased. Therefore, the previously reported conditions of preparative
      electrophoresis of microsomes, using concentrated (12%) polyvinylpyrrolidone
      (PVP) solutions, while solving the problem of non-entrance of large particles
      into "sieving media", do not provide adequate resolving capacity, as exemplified
      by failure of the microsome preparation used, to resolve in the manner of gels or
      dilute solutions. The present report provides the conditions under which the HPGE
      1000 apparatus can be preparatively applied when the electrophoretic separation
      is effectively conducted in a dilute polymer solution. The isolation of three
      microsome components under those conditions constitutes the first application of
      "particle sieving", i.e., a separation due preponderantly to size and shape
      differences, at a preparative scale.

PMID- 9194607
TI  - Electrophoretic analysis of the "cross-class" interaction between novel
      inhibitory serpin, squamous cell carcinoma antigen-1 and cysteine proteinases.
AB  - We investigated the "cross-class" interaction between cysteine proteinases and a
      novel inhibitory serpin, recombinant squamous cell carcinoma (rSCC) antigen-1,
      which inhibits a serine proteinase, chymotrypsin. rSCC antigen-1 inhibited the
      cysteine proteinases, papain, papaya proteinase IV and cathepsin L.
      Interestingly, although rSCC antigen-1 formed sodium dodecyl sulfate (SDS)- and
      heat-stable complexes with chymotrypsin, rSCC antigen-1 gave the 40 kDa fragment
      and small molecular mass peptide by incubation with papain without forming an SDS
      and heat-stable complex. The cleavage was observed between the Gly353-Ser354
      bond, indicating that rSCC antigen-1 interacts with cysteine proteinases not at
      the predicted reactive site P1-P1' portion (Ser354-Ser355), but at the Gly353
      Ser354 of the P2-P1 portion. These findings promote understanding of the "suicide
      inhibition" mechanism of SCC antigen-1 against cysteine proteinases.

PMID- 9194608
TI  - Alternative method of subtyping the A subunit of coagulation factor XIII
      (FXIIIA).
AB  - An alternative isoelectric focusing method for the A subunit of coagulation
      factor XIII (FXIIIA) subtyping is described which employs three different carrier
      ampholytes, pH 4-6.5, pH 5-6 and pH 5-8 (2:2:1), and sample application at the
      anode. With this technique ten common subtypes, including a variant, were clearly
      and reliably identified in Japanese and Chinese population samples.

PMID- 9194609
TI  - Computer analysis of two-dimensional electrophoresis gels: a new segmentation and
      modeling algorithm.
AB  - The complexity of the spot patterns of two-dimensional electrophoresis gels made
      it necessary to use image processing techniques to analyze the gels. An important
      issue in the analysis is the detection and quantification of the protein spots.
      In this paper we describe a new technique to segment and model the different
      spots. For the segmentation of a gel into its different spot regions we apply a
      watershed technique, which is robust and efficient. For the quantification of the
      spots, a new spot model is constructed, based on diffusion principles. Besides
      the advantage of having a physical interpretation, the model is demonstrated to
      be superior to the commonly used Gaussian models.

PMID- 9194610
TI  - A new method to assign immunodetected spots in the complex two-dimensional
      electrophoresis pattern.
AB  - A new, easy method for the immunodetection of specific antigens in two
      dimensional electrophoresis (2-DE) is described. Areas of 2-DE gels containing
      antigens of interest are electrophoretically transferred to polyvinylidene
      difluoride membranes, immunostained with specific antibodies using Fast Red or 5
      bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium as detection systems
      and counterstained with Coomassie Brilliant Blue. In contrast to conventional
      methods, it is possible to use this procedure to exactly assign immunoreacting
      proteins on a single blot to their corresponding and surrounding blue-stained
      protein spots.

PMID- 9194611
TI  - Dilated cardiomyopathy-associated proteins and their presentation in a WWW
      accessible two-dimensional gel protein database.
AB  - High resolution two-dimensional electrophoresis (2-DE) and computer-assisted
      image analysis were used to screen 13 patients suffering from dilated
      cardiomyopathy (DCM) versus 15 control patients for quantitative and qualitative
      differences in their myocardial protein expression. Right atrial tissue samples
      were obtained from end-stage failing explanted hearts and control hearts. Fifty
      two spots differed significantly in average intensity between the DCM and the
      control groups. Myosin light chain 2, ventricular (MLC2) and heat shock protein
      HSP 27 were identified by protein microsequencing and gel map comparison with
      other databases. These proteins were found to be characteristic protein markers
      for DCM in the right atrium. In DCM patients, the spot intensity (protein
      abundance) of MLC2 is increased to 336% and HSP 27 is decreased to 59%, compared
      to the control group. The HEART-2DPAGE, a World Wide Web-accessible 2-DE
      database, was used and extended for the presentation of these disease-associated
      proteins. Retrievable via Internet we present a list of disease-associated
      proteins, their altered level of expression in DCM, and their position on a right
      atrial protein pattern. The accession number to protein sequence databases
      confers a connection to databases like SWISS-PROT to obtain a detailed functional
      and structural description of disease-associated proteins. New DCM-associated
      proteins are detected and their presentation in a 2-DE gel protein database is
      described.

PMID- 9194612
TI  - Changes in nuclear protein composition in response to chronic electrical
      stimulation of skeletal muscle.
AB  - The adaptive response of skeletal muscle to increased functional demand involves
      phenotypic changes that affect contractile properties, energy metabolism and
      calcium kinetics. Some of these changes are known to be initiated at a pre
      translational level, but the underlying regulatory mechanisms have not yet been
      identified. In this study we used chronic electrical stimulation (10 Hz,
      continuous) to initiate fast-to-slow muscle fibre-type transformation, and two
      dimensional electrophoresis (2-DE) to assess changes in nuclear protein
      composition after 24 and 72 h. We report an early and sustained increase in the
      level of a 3 kDa protein in stimulated fast muscle (n = 6). The presence of the
      same protein in control slow muscle is consistent with a possible functional role
      in the determination of the slow phenotype.

PMID- 9194613
TI  - High resolution two-dimensional electrophoretic analysis of urinary proteins of
      patients with prostatic cancer.
AB  - In an attempt to identify marker(s) for prostatic cancer, proteins in urines of
      normal and prostatectomized males and in men with cancerous prostate were
      analyzed. Only urines collected with protease inhibitors were examined. Two
      dimensional (2-D) gel electrophoresis was used for high resolution separation of
      proteins and the electrophoretograms were either developed by double stain or the
      proteins were electrophoretically transferred onto nitrocellulose for
      immunological identification. The pool of each group exhibited similar relative
      positions of major protein spots. The study of normal and prostatectomized men
      identified two proteins denoted as A (36 kDa, pI 6-6.5) and B (23 kDa, pI 6.6),
      which were undetectable in the latter group. A visual comparison of the patterns
      of normals and patients with cancerous prostate revealed that both these proteins
      were undetectable in urines of men with malignant prostatic carcinoma (PCA) and
      benign prostatic hyperplasia (BPH) and hence may be useful in identifying
      prostatic carcinoma. Also, while protein C 43.5 kDA, pI 6-6.6) was discerned in
      normals its abundance, along with those of proteins D (40 kDa, pI 6-6.4) and E
      (26.5 kDa, pI 6-6.7), appeared to be higher in BPA than in PCA. Protein F (18-28
      kDa, pI 4-5.5) was found in patients with BPH but was undetected in normals and
      men with PCA. Hence, it may become useful in distinguishing BPH from PCA. All the
      proteins, A to F, appear to be previously unidentified. Their further
      characterization is warranted.

PMID- 9194614
TI  - Comparison of natural and recombinant isoforms of grass pollen allergens.
AB  - More than 95% of grass pollen allergic patients possess IgE antibodies against
      grass group I, a heterogeneous group of glycoproteins found in all temperate
      grasses. We studied the structural variability of the group I allergens in single
      species and among different grasses. By 2-DE blotting using patients' IgE and
      monoclonal antibodies, we detected IgE-reactive isoforms with molecular masses
      between 32 and 37 kDa and focusing in a wide pI ranging from 4.7 to 7.6. While
      the group I allergens of timothy grass (Phl p 1) were composed of 37 and 35 kDa
      components, only single isoforms were found for ryegrass (Lol p 1) and velvet
      grass (Hol l 1): 32 and 34 kDa, respectively. By N-terminal microsequencing we
      determined single amino acid substitutions in different-sized group I allergens.
      The post-translational modifications (one N-glycosylation site, two hydroxylated
      proline residues and seven cysteine residues for potential disulfide formations),
      which contribute to IgE reactivity, were identical in all. From the cDNA
      sequences we deduced protein sequence homologies > 90%, a result which might
      explain the high IgE cross-reactivity among the grasses. In order to test whether
      recombinant group I grass allergens can act as substitutes for the natural forms,
      we expressed rPhl p 1 in E. coli and in P. pasteuris. 2-DE immunoblotting again
      demonstrated a microheterogeneity in molecular mass and pI. While the E. coli
      products were free from post-translational modifications, rPhl p 1 from Pichia is
      a heterogeneous glycoprotein fraction with a carbohydrate content of about 15%.
      This rPhl p 1 is hyperglycosylated compared to the nPhl p 1, which only has a 5%
      carbohydrate content.

PMID- 9194615
TI  - Identification and characterization of wheat grain albumin/globulin allergens.
AB  - Bakers' asthma, an immediate-type allergic response to the inhalation of cereal
      flours, is an important occupational disease among workers of the baking and
      milling industries, and the salt-soluble proteins of wheat and rye flour dust are
      considered the most relevant allergens. In order to identify and characterize the
      major IgE-binding proteins, the polypeptide composition of the albumin/globulin
      protein fraction obtained from different cultivars was analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and high-resolution two
      dimensional polyacrylamide gel electrophoresis with immobilized pH gradients in
      the first dimension (IPG-Dalt), followed by immunoblotting with sera from
      asthmatic bakers. Relevant allergens were isolated by micropreparative IPG-Dalt
      and blotting onto polyvinylidenedifluoride membranes and identified by amino acid
      composition analysis or N-terminal amino acid sequence analysis. SDS-PAGE, IPG
      Dalt, and immunoblotting demonstrated that the sera of the bakers allergic to
      flour contained IgE antibodies which bound to numerous albumin/globulin
      polypeptides in the 70, 55, 35, 26-28, and 14-18 kDa areas. More detailed
      investigations using IPG-Dalt revealed cultivar-specific differences in IgE
      binding. It was also demonstrated that the majority of the allergens were not
      single polypeptide spots, but consisted of up to ten isoforms of similar
      molecular mass but different isoelectric points. Amino acid composition analysis
      and N-terminal amino acid sequence analysis, which were performed for nine
      allergens located in the 14-18, 26-28, and 35 kDa areas, revealed homologies to
      amylase/protease inhibitors, acyl-CoA oxidase and fructose-bisphosphate-aldolase
      from wheat, barley, maize, and rice, respectively.

PMID- 9194616
TI  - Analysis of proteins from different phase variants of the entomopathogenic
      bacteria Photorhabdus luminescens by two-dimensional zymography.
AB  - Two-dimensional zymography which combines two-dimensional electrophoresis with
      zymography was used to analyze proteases and other proteins produced by different
      phase variants of two strains of Photorhabdus luminescens. Both the primary and
      secondary phases of P. luminescens strains Hp and Hm secreted proteases. The
      protease in P. luminescens Hp has a molecular weight (Mr) of 57,000 and an
      isoelectric point (pI) of 4.4 whereas that in P. luminescens Hm has an Mr of
      59,000 and pI of 4.9. Several putative protease degradation products were clearly
      visible in the zymograms from both bacterial strains. Two-dimensional zymography
      also showed that several secretory proteins were present only in particular phase
      variants and therefore could be used as specific markers. Unexpectedly, the two
      dimensional zymography revealed that a nonsecretory protease with an Mr of 47,000
      and a pI of 4.0 was present in the cell extracts of all phases of both P.
      luminescens Hp and Hm. The application of the two-dimensional zymography for the
      identification of other enzymes was also discussed.

PMID- 9194617
TI  - Comparing the clinical utility of GnRH antagonist to GnRH agonist in an oocyte
      donation program.
AB  - A potent gonadotropin-releasing hormone (GnRH) antagonist (Nal-Glu) was
      administered to downregulate the pituitaries of oocyte donors (n = 15) and block
      their midcycle luteinizing hormone surges. Donors received Nal-Glu at a dose of
      50 microg/kg/day i.m., beginning when lead follicles reached a mean diameter of
      14 mm. All donors had previously undergone controlled ovarian hyperstimulation
      cycles using GnRH agonist (leuprolide acetate) administered subcutaneously
      beginning during the midluteal phase. Ovarian stimulation was performed using
      human menopausal gonadotropin (hMG). Compared to previous stimulated cycles using
      agonist and hMG, cycles with antagonist and hMG demonstrated a significant
      decrease in the amount of hMG required for follicle stimulation (24.7 +/- 1.8 vs.
      31.3 +/- 2.5 ampules; p < 0.05). There was also a significant reduction in the
      number of patient visits necessary per cycle (5.1 +/- 1.4 vs. 9.3 +/- 1.1; p <
      0.05) and the required duration of treatment to accomplish a cycle (27.1 +/- 5.3
      vs. 11.3 +/- 1.3 days; p < 0.05). However, there were no differences noted in the
      number of oocytes retrieved (10.7 +/- 4.5 vs. 13.0 +/- 6.3), the fertilization
      rate of oocytes (60.3 +/- 10.2 vs. 53.9 +/- 11.6%), or the number of embryos
      obtained per recipient (5.5 +/- 3.2 vs. 7.6 +/- 5.3). Clinical pregnancies
      occurred in 7 of 15 transfer cycles to recipients. There were no serious adverse
      side effects experienced by donors using antagonist. We conclude that the use of
      GnRH antagonist significantly reduces the amount of medication and the time
      required for ovarian hyperstimulation and that is a useful adjunct in cycling
      oocyte donors.

PMID- 9194618
TI  - Relative potency of nitrovasodilators on human placental vessels from normal and
      preeclamptic pregnancies.
AB  - The relative potency of glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and
      S-nitroso-N-acetylpenicillamine (SNAP) was determined in human placental arteries
      and veins from normotensive gestants and preeclamptic women. This study
      demonstrates that the potency of the three nitrovasodilators is similar in normal
      and preeclamptic pregnancies. GTN and SNP behave as strong vasodilators and were
      significantly more potent as relaxant of venous than arterial segments.
      Meanwhile, SNAP was 1 order of magnitude less potent than GTN and SNP and is
      equally effective in reducing induced tone in arterial or venous segments. These
      observations suggest that the placental vessels obtained from normotensive and
      preeclamptic gestants resulted equally sensitive to the relaxant effect of each
      nitric oxide donor drug, and nitrovasodilators appear to be an interesting option
      for further clinical research on the prevention and management of preeclampsia.

PMID- 9194619
TI  - Value of the maternal interleukin 6 level for determination of histologic
      chorioamnionitis in preterm delivery.
AB  - The present study examined whether maternal serum cytokine levels are useful for
      the diagnosis of histologic chorioamnionitis. The blood samples of 29 women who
      delivered preterm between 22 and 34 weeks of gestation were collected at
      delivery, and placentas were histopathologically examined for chorioamnionitis.
      The interleukin (IL) 6 titer was higher in 18 mothers with histologic
      chorioamnionitis (median 12.0 pg/ml, range 4.9-63.5 pg/ml) than that in 11
      mothers without histologic chorioamnionitis (median 3.5 pg/ml, range 1.7-14.9
      pg/ml; p < 0.0001). The C-reactive protein (CRP) titer also differed
      significantly between these two groups (chorioamnionitis group: median 5.2 mg/dl,
      range 0.1-12.3 mg/dl; no chorioamnionitis group: median 0.2 mg/dl, range 0.1-0.5
      mg/dl; p = 0.0001). The IL-6 titer showed better clinical diagnostic indices and
      a higher odds ratio (9.78, 95% confidence interval 1.50-63.82) than did CRP
      (3.26, 95% confidence interval 1.22-8.67). The levels of IL-8, monocyte
      chemotactic and activating factor, and soluble IL-6 receptor did not differ
      between the two groups. These data suggest that the level of maternal serum IL-6
      is more useful than other markers, including CRP, for the identification of women
      at risk of impending preterm labor with histologic chorioamnionitis.

PMID- 9194620
TI  - Antenatal diagnosis of aberrant umbilical vessels.
AB  - OBJECTIVE: To evaluate the antenatal screening of aberrant umbilical vessels and
      assess the association of fetal abnormality with these entities. STUDY DESIGN:
      444 pregnant women were studied with routine obstetric ultrasound and Doppler
      color flow imaging in late second trimester or early third trimester. Fetal
      growth and anomaly, and the number of umbilical cord vessels were screened.
      RESULTS: Out of 444 subjects, 3 cases with discordant umbilical artery, 2 with
      four vessels in the umbilical cord, and 1 with single umbilical artery were
      detected (1.4%). Fetal anomaly was noted in 2 of 6 cases with aberrant umbilical
      vessels (33.3%). CONCLUSION: These results suggest that antenatal screening of
      umbilical cord vessels is necessary for detection of fetal anomalies.

PMID- 9194622
TI  - A study to determine whether serum follicle-stimulating hormone can be a marker
      for ovarian hyperresponse to follicle-maturing drugs for in vitro fertilization.
AB  - The study presented herein evaluated whether 26 of 122 consecutive women who tend
      to hyper-respond (serum estradiol >4,000 pg/ml or >30 follicles) following
      controlled ovarian hyperstimulation for in vitro fertilization have higher serum
      FSH levels at certain critical stages during the follicular phase. Baseline day-2
      serum FSH and blood levels taken on days 5 and 6 of human menopausal gonadotropin
      therapy were not different in the hyper-responders from those responding
      normally. The only significant difference in serum FSH was seen on the day of
      human chorionic gonadotropin where it was actually lower in the hyper-responders.
      Thus, there does not appear to be a critical serum FSH level which would dictate
      a decrease in gonadotropins to prevent hyper-response.

PMID- 9194621
TI  - Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal
      calcium metabolism and bone mineral content.
AB  - A prospective study was designed to determine whether calcium homeostasis and
      bone mineral content were affected adversely in preterm infants born to mothers
      receiving long-term antenatal therapy with magnesium sulfate. Preterm infants
      born to mothers receiving long-term antenatal therapy with magnesium sulfate and
      requiring prolonged bed rest for preterm labor were compared with infants of
      mothers not receiving magnesium sulfate but in whom prolonged bed rest was also
      required. Serum magnesium, calcium, phosphorus, osteocalcin, and parathyroid
      hormone were measured in infants at 0, 24, 48, and 72 h after delivery. Bone
      mineral content of the distal radius was measured 1 week postnatally and at term
      equivalent postmenstrual age. Maternal serum mineral status indices obtained near
      delivery and bone indices were compared with those of their infants. The clinical
      characteristics and morbidities of the infants were similar between groups. We
      observed significantly greater serum concentrations of magnesium, phosphorus, and
      osteocalcin during the 72 h after delivery and a lower serum calcium
      concentration which normalized by 72 h in preterm infants whose mothers were
      treated with magnesium sulfate compared with infants whose mothers did not
      receive magnesium sulfate. Both groups, however, had similar radius bone mineral
      content measurements and anthropometric indices after delivery. These data
      suggest that although preterm infants born to mothers treated with magnesium
      sulfate have delayed clearance of magnesium and phosphorus, they have a
      normalization of serum calcium by 72 h after delivery and no significant
      differences in bone mineral content after delivery compared with infants whose
      mothers do not receive magnesium sulfate.

PMID- 9194623
TI  - Localization of T cells, interferon-gamma and HLA-DR in eutopic and ectopic human
      endometrium.
AB  - OBJECTIVES: Immunologic mechanisms are implicated in the pathogenesis of
      endometriosis and endometriosis-associated reproductive failure. The purpose of
      this study was to describe key immune response elements in eutopic and ectopic
      endometrium and to test the hypothesis that expression of CD3-positive T cells,
      the T-helper 1-type cytokine, IFN-gamma, and the antigen presentation marker, HLA
      DR, vary throughout the menstrual cycle in eutopic endometrium and are more
      abundantly expressed in ectopic than in eutopic endometrium. METHODS: Eutopic and
      ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were
      compared with hysterectomy specimens from 7 women with adenomyosis and 10 women
      without endometriosis or endometrial pathology. Tissues were formalin-fixed,
      paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline
      phosphatase technique and antibodies to human CD3, IFN-gamma, and HLA-DR. Eutopic
      endometrial samples were histologically divided into menses (n = 5),
      proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues
      (spleen) and negative controls (no primary antibody) were used in each
      experiment. RESULTS: T cells, IFN-gamma and HLA-DR-positive cells were observed
      in eutopic endometrial samples throughout the menstrual cycle. Glandular
      epithelium was CD3-negative except for CD3-positive cells surrounding and
      occasionally interdigitating between glandular epithelium. Glandular epithelium
      was IFN-gamma-positive and HLA-DR-positive in all phases except the proliferative
      phase. Staining was more often observed in the basalis than in the functionalis
      layer, ranging from patchy staining to the entire gland. T cells, IFN-gamma, and
      HLA-DR-positive stromal cells were more abundant in secretory endometrium than in
      proliferative samples. CD3, IFN-gamma, and HLA-DR-positive cells were scattered
      throughout the myometrium and concentrated in vessels. Higher intensity staining
      was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive
      cells forming aggregates around IFN-gamma and HLA-DR-positive glands. The
      intensity of IFN-gamma staining in ectopic endometrium was similar to the
      intensity of staining observed in menstrual and late secretory basalis samples
      from eutopic endometrium. CONCLUSIONS: The results of this observational study
      suggest that activated T cells, IFN-gamma and upregulation of antigen
      presentation may play a role in normal endometrial physiology. The increased
      number of T cells, expression of IFN-gamma, and enhanced antigen presentation in
      ectopic compared to eutopic endometrium support the concept that cellular immune
      activation is involved in endometriosis and its sequelae.

PMID- 9194624
TI  - Postoperative GnRH analog treatment for the prevention of recurrences of uterine
      myomas after myomectomy. A pilot study.
AB  - Sixty-five patients with uterine myomas were studied after surgery to investigate
      the effect of periodic GnRH analog treatment on the prevention of recurrences. A
      group of patients was treated by leuprolide acetate depot 3 months a year for 3
      years. At the end of treatment, these patients showed a significantly reduced
      uterine volume and myoma recurrence rate as compared to untreated patients. A
      role of GnRH analogs in the clinical prevention of myoma recurrence could be
      suggested.

PMID- 9194625
TI  - Peoscopic diagnosis of flat condyloma and penile intraepithelial neoplasia.
      Clinical manifestation.
AB  - Peoscopy was performed in order to assess penile lesions in the male sexual
      partners of 326 women with cervical intraepithelial neoplasia (CIN) or flat
      condyloma (FC). Each patient was submitted to a careful naked-eye inspection,
      peoscopy and biopsy of any suspicious lesion which was confirmed histologically
      and immunohistochemically. A brush cytologic examination of the distal portion of
      the urethra was also performed. The distribution of penile lesions was as
      follows: (1) 8 patients with herpes virus infection; (2) 37 patients with
      condyloma accuminata (CA); (3) 89 patients with FC; (4) 51 patients with FC and
      CA; (5) 18 patients with penile intraepithelial neoplasia grade 1 (PIN-I); (6) 2
      patients with PIN-II; (7) 17 patients with PIN-III; (8) 92 patients with no
      penile lesions; (9) 7 patients with human papilloma virus infection of papillae
      coronae glandis, and (10) 5 patients with FC of the distal portion of the
      urethra. Naked-eye inspection revealed the presence of penile lesions in 39 of
      233 patients (16.73%). Peoscopic examination revealed the presence of penile
      lesions in 233 of 326 patients (71.48%). In 135 of 155 patients the peoscopic
      findings were in accordance with the histologic diagnosis (87.09%).
      Immunohistochemical (by indirect peroxidase-antiperoxidase method) detection of
      virus antigens was positive in 16 of 34 patients (47.03%). It is concluded that
      peoscopy of the male sexual partners of women with CIN or FC should be performed
      to better assess the treatment used in the couple.

PMID- 9194626
TI  - A multivariate analysis of clinical and morphological prognostic factors in
      squamous cell carcinoma of the vulva.
AB  - Clinical and histological data of 168 patients with squamous cell carcinoma of
      the vulva were analyzed with respect to survival. 151 patients underwent surgery,
      12 patients were treated with primary radiation and in 5 patients no treatment
      was performed. Follow-up lasted from at least 2 up to 22 years' posttreatment. In
      univariate analysis, the following factors were highly significant: presurgery
      lymph node status, tumor infiltration beyond the vulva, tumor grading,
      histological inguinal lymph node status, pre- and postsurgery tumor stage, depth
      of invasion and tumor diameter. In the multivariate analysis (Cox regression),
      the most powerful factors were shown to be histological inguinal lymph node
      status, tumor diameter and tumor grading. The multivariate logistic regression
      analysis worked out as main prognostic factors for metastases of inguinal lymph
      nodes: presurgery inguinal lymph node status, tumor size, depth of invasion and
      tumor grading. Based on these results, tumor biology seems to be the decisive
      factor concerning recurrence and survival. Therefore, we suggest a more
      conservative treatment of vulvar carcinoma. Patients with confined carcinoma to
      the vulva, with a tumor diameter up to 3 cm and without clinical suspected lymph
      nodes, should be treated by wide excision/partial vulvectomy with ipsilateral
      lymphadenectomy.

PMID- 9194627
TI  - Applying the herpes simplex virus thymidine kinase/ganciclovir approach to
      ovarian cancer: an effective in vitro drug-sensitization system.
AB  - Ovarian cancer is a major clinical problem with no rewarding treatment protocol
      currently available. In other malignancies transfer of the herpes simplex virus
      thymidine kinase (HSV-tk) gene into tumor cells using a viral vector followed by
      administration of ganciclovir (GCV) provides a potentially effective strategy for
      treatment. In this work human ovarian epithelial cancer cell lines were infected
      with a recombinant adenoviral vector expressing the HSV-tk (AdRSV-tk) and were
      rendered sensitive to doses of GCV that were 100-200 times less than for
      untransfected cells. A strong bystander effect was noted with significant killing
      at a ratio of infected:uninfected cells of only 1:20 and maximal killing at 1:3.
      Normal human ovarian surface epithelial cells were also highly sensitive to the
      AdRSV-tk/GCV system. This study demonstrates the potential efficacy of the HSV
      tk/GCV approach in ovarian cancer gene therapy.

PMID- 9194628
TI  - Reduction in the size of a uterine leiomyoma following discontinuation of an
      estrogen-progestin contraceptive.
AB  - The effects of estrogen-progestin oral contraceptives on the volume of uterine
      leiomyomata is not well characterized. In this case report, a 45-year-old woman
      with a symptomatic uterine leiomyoma was observed to have a 47% reduction in
      myoma volume after discontinuation of an oral contraceptive. The volume of
      uterine leiomyomata may be influenced by oral contraceptives.

PMID- 9194629
TI  - Multiple giant fibroadenomas: clinical presentation and radiologic findings.
AB  - We describe the case of a 25-year-old Caucasian woman suffering from unilateral
      enlargement of the breast. Morphologic evaluation of various imaging modalities
      including mammography, ultrasound, and magnetic resonance imaging suggested a
      benign tumor embedded in stromal tissue. The time course of the Gd-DTPA uptake in
      dynamic magnetic resonance imaging, however, was also compatible with a malignant
      lesion. Postoperative pathological examination revealed multiple giant
      fibroadenomas, a rare disease, usually encountered in black female adolescents.
      Radiologic presentation, differential diagnosis, and morphologic findings are
      discussed, and a review of the literature is contained herein.

PMID- 9194630
TI  - Attitudes to clinical andrology: a time for change.

PMID- 9194631
TI  - Declining clinical andrology: fact or fiction?

PMID- 9194632
TI  - Clinical andrology is important for treatment of male infertility with ICSI.

PMID- 9194633
TI  - Molecular biology in the modern work-up of the infertile male: the time to
      recognize the need for andrologists.

PMID- 9194634
TI  - Do the fastest concepti have a shorter life span?
AB  - An evolutionary hypothesis based on an 'antagonist pleiotropy' or 'disposable
      soma' mechanism is put forward to explain differences in longevity between
      species, strains, and sexes. Data from several congenic mouse strains and
      mammalian species suggest that there may be an association between cleavage rate
      of concepti and longevity, in such a way that concepti from species, strains or
      the sex (male) with the fastest cleavage rates have shorter life spans. The major
      histocompatibility complex (MHC) and, in particular, the conceptus development
      gene (Ped) together with several Y-linked genes that are expressed during the
      preimplantation stages of development may play an important role in determining
      or modulating longevity in mammals. Notwithstanding, effects of other loci as
      well as environmental factors on conceptus development and longevity cannot be
      ignored.

PMID- 9194635
TI  - Activation of plasma kinin system correlates with severe coagulation disorders in
      patients with ovarian hyperstimulation syndrome.
AB  - The aim of this study was to evaluate status of plasma kinin system in patients
      with ovarian hyperstimulation syndrome (OHSS), in order to investigate whether
      activation of the plasma kinin system correlates with increased blood
      coagulability. In the first part of the study, concentrations of plasma
      prekallikrein (PK) in OHSS cycles (n = 13) were monitored from the day of human
      chorionic gonadotrophin (HCG) administration to the mid-luteal phase, and were
      compared with those of control cycles (n = 17). The average value of PK in OHSS
      cycles began to decrease on day 8, and by day 10 was significantly lower than
      that of control cycles (86 +/- 6 versus 106 +/- 4%, P <0.01). The time course of
      changes in PK concentration correlated well with the clinical condition of OHSS
      patients. In the second part of the study, we obtained data from 26 patients who
      were hospitalized because of severe OHSS, to investigate the correlation between
      PK and other haemostatic markers. OHSS patients with severe PK reduction (<80%
      normal, n = 9) demonstrated significantly higher values of plasma thrombin
      antithrombin III and plasmin-alpha2 antiplasmin, and more severe
      haemoconcentration, compared to those OHSS patients who had no reduction in PK (n
      = 17). In conclusion, our data suggest that activation of the plasma kinin system
      occurs specifically and occasionally in OHSS patients, and is associated with
      increased blood coagulability. Thus, when an OHSS patient demonstrates a low
      value of plasma PK, more careful management is required to prevent thromboembolic
      complications.

PMID- 9194636
TI  - Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing
      hormone, melatonin and cortisol in infertile women with subclinical
      hypothyroidism.
AB  - Preliminary data have suggested that female infertility due to corpus luteum
      insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid
      stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH)
      stimulation]. L-Thyroxine supplementation has been recommended to achieve
      pregnancies in subclinical hypothyroid women. This controlled study was carried
      out in order to investigate the biochemical diagnosis of subclinical
      hypothyroidism as a possible infertility factor. Five infertile patients (aged 25
      36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml)
      or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years)
      with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and
      no history of infertility were studied in the early follicular phase. In the pre
      study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of
      subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle
      function of patients and controls was compared by the method of LH pulse pattern
      analysis. Therefore blood samples were drawn every 10 min during a 24 h period.
      Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end
      of the 24 h blood sampling period confirmed the difference in stimulated TSH
      values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH
      and prolactin showed no differences between patients and controls for pulse
      frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean.
      Even the hypothyroid patient had a normal LH pulse pattern. Additional
      measurement of melatonin in pooled sera every 30 min gave the well-documented
      diurnal profiles during day and night for both groups. Patients had significantly
      higher melatonin values at seven time points during the night. Peaks for LH, TSH,
      prolactin and cortisol were correlated with the sleep stages wake, rapid eye
      movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in
      female infertility cannot be explained by subclinical hypothyroidism and thus
      should not be treated with L-thyroxine for fertility reasons.

PMID- 9194637
TI  - Endocrine abnormalities in ovulatory women with polycystic ovaries on ultrasound.
AB  - Polycystic-appearing ovaries (PAO) on ultrasound have been described in a variety
      of endocrinopathies and also occur in ovulatory women. By some investigators this
      is merely referred to as 'PCO' (polycystic ovaries). Although there is
      controversy in this regard, we do not consider women with PAO/PCO who have no
      known endocrine disturbance to have polycystic ovary syndrome (PCOS) and
      therefore prefer not to use the term 'PCO' which is often equated with PCOS. We
      studied 15 ovulatory women with normal-appearing (NAO) ovaries on ultrasound and
      15 matched ovulatory women with PAO/PCO. Compared to ovulatory women, 25 other
      women were studied who were considered to have PCOS. Of these, 15 were overweight
      and 10 were of normal weight. All the PCOS women had serum concentrations of
      luteinizing hormone (LH), testosterone, unbound testosterone, androstenedione and
      dihydroepiandrosterone sulphate (DHEAS) which were significantly higher (P <
      0.01) than values in the normal women, regardless of ovarian morphology. These
      values were similar in the two groups of ovulatory women with NAO and PAO/PCO.
      Fasting insulin was elevated in women with PCOS with increased body weight (P <
      0.01) and was higher than in ovulatory women with NAO and PAO/PCO and than in
      women of normal weight with PCOS. Serum insulin-like growth factor (IGF)-I and
      binding protein (BP)-3 were similar in all groups but serum IGFBP-1 was
      significantly (P < 0.01) lower in those women with PCOS with increased body
      weight, compared to all other groups. Compared to values in ovulatory women with
      NAO, serum IGFBP-1 was also significantly (P < 0.05) lower in women with PAO/PCO
      and those women with PCOS of normal weight. These lower values were similar in
      women with PAO/PCO and in normal weight women with PCOS. On an individual basis,
      an elevation of at least one serum androgen value was found in 33% of women with
      PAO/PCO. These data confirm that increased body weight accentuates the metabolic
      alterations in PCOS, but suggest that subtle endocrine disturbances, similar to
      those that are found in PCOS, may be uncovered in up to a third of ovulatory
      women with PAO/PCO. It appears that a disturbance of the IGF/IGFBP-1 axis is
      common and apparently closely associated with alterations in ovarian morphology.

PMID- 9194638
TI  - 17-Hydroxyprogesterone responses to gonadotrophin-releasing hormone agonist
      buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of
      adrenal and ovarian cytochrome P450c17alpha dysregulation.
AB  - Abnormal regulation of cytochrome P450c17alpha causes the exaggerated secretion
      of ovarian androgens in polycystic ovary syndrome (PCOS). This enzyme is active
      in both the ovaries and adrenal glands. We examined whether there is an abnormal
      regulation of cytochrome P450c17alpha in the adrenal gland by investigating the
      relationship of 17-hydroxyprogesterone (17-OH progesterone) hyperresponsiveness
      to the gonadotrophin releasing hormone (GnRH) agonist, buserelin, testing with 17
      OH progesterone response to adrenocorticotrophic hormone (ACTH) in PCOS. In all,
      68 women with PCOS and 24 normal women were included in the study. Ultrasound,
      clinical and hormonal parameters were used to define PCOS. 17-OH progesterone
      response to ACTH was measured in all the women. In 52 of the 68 women with PCOS,
      17-OH progesterone response to buserelin was measured. The mean basal 17-OH
      progesterone concentrations were similar in both PCOS and control groups. PCOS
      women had significantly higher net increment in 17-OH progesterone after ACTH
      administration (P<0.02). No significant correlations were found between the peak
      17-OH progesterone values, the net increments in 17-OH progesterone and the area
      under the 17-OH progesterone-response curves after ACTH stimulation and buserelin
      test. Although 17-OH progesterone response to ACTH was significantly higher in
      the patients with PCOS than in the control subjects, the lack of relationship
      between 17-OH progesterone response to GnRH agonist buserelin and 17-OH
      progesterone response to ACTH stimulation suggests that the dysregulation of the
      cytochrome P450c17alpha enzyme may not play a role in adrenal androgen excess
      seen in PCOS.

PMID- 9194639
TI  - Serum concentrations of oestradiol-17beta, progesterone, relaxin and chorionic
      gonadotrophin during blastocyst implantation in natural pregnancy cycle and in
      embryo transfer cycle in the rhesus monkey.
AB  - The present study was undertaken to assess the temporal association between the
      profiles of serum concentrations of oestradiol-17beta, progesterone, chorionic
      gonadotrophin (CG) and relaxin in pregnancies established naturally, and after
      embryo transfer, as well as in failed pregnancies in rhesus monkeys. In naturally
      mated cycles (group 1) a conception rate of 75% was obtained. In group 1, the
      mean day of CG detection in serum was 11.5 +/- 1.9 day post-ovulation, and for
      relaxin, 9.0 +/- 2.5 day post-ovulation. In group 2, embryo transfer to
      synchronous, non-mated surrogate recipients was performed; seven embryo transfer
      cycles yielded three pregnancies which were allowed to continue to term and
      normal infants were delivered. In embryo transfer cycles the mean day of CG
      detection was 14.8 +/- 1.8 day post-ovulation, and for relaxin, 11.4 +/- 2.6 day
      post-ovulation. A delay of about 3 days was observed in the appearance in
      circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between natural mated
      and embryo transfer conception cycles. Significant differences (P < 0.05 for
      progesterone and P < 0.03 for oestradiol) were obtained for the areas under the
      curves for progesterone and oestradiol between days 12 and 16 in conception
      cycles compared with failed pregnancies. These data provide the first observation
      of the normal hormonal signals associated with maternal recognition of
      transferred embryos during the peri-implantation period, and suggest that the use
      of such an experimental primate embryo transfer model may help to elucidate
      components of maternal and embryonic signal-response mechanisms during embryo
      implantation.

PMID- 9194640
TI  - Interleukin-12- and interleukin-2-stimulated release of interferon-gamma by
      uterine CD56++ large granular lymphocytes is amplified by decidual macrophages.
AB  - Numerous studies have suggested that interferon-gamma (IFN-gamma) exhibits an
      inhibitory effect on conceptus development during pregnancy, and recent
      investigations have shown that decidual CD56++, CD16- large granular lymphocytes
      (LGL) contain mRNA for IFN-gamma. We have investigated the influence of exogenous
      interleukin-12 (IL-12) and interleukin-2 (IL-2) on IFN-gamma secretion by
      cultivated LGL and macrophages isolated from first trimester human decidua. The
      effect of decidual macrophages on IFN-gamma secretion by LGL was also assessed
      using co-incubation experiments. Neither IL-12 nor IL-2 stimulated the secretion
      of IFN-gamma by decidual macrophages. IL-12 alone, but not IL-2 alone, stimulated
      the release of IFN-gamma by LGL. However, IL-2 acted synergistically with IL-12
      to enhance the release of IFN-gamma by LGL. Unstimulated and IL-12- and IL-2
      stimulated LGL incubated with macrophages exhibited a marked increase in
      secretion of IFN-gamma compared to those in monoculture. This effect was also
      seen when the LGL and macrophages were separated by a semi-permeable membrane.
      The results suggest that interactions between decidual LGL and macrophages,
      possibly mediated by soluble factors, could play a role in regulating IFN-gamma
      secretion at the materno-fetal interface and thus contribute to the control of
      invasion by the trophoblast.

PMID- 9194641
TI  - Humoral immune response to membrane components of Chlamydia trachomatis and
      expression of human 60 kDa heat shock protein in follicular fluid of in-vitro
      fertilization patients.
AB  - Recent evidence suggests that Chlamydia trachomatis can persist in the female
      upper genital tract in an unculturable state. Since unsuspected C. trachomatis
      infection has been associated with adverse in-vitro fertilization (IVF) outcome
      we sought to detect further evidence of C. trachomatis in the genital tracts of
      women undergoing IVF. The prevalence and distribution of antibodies to the major
      structural proteins of C. trachomatis in paired follicular fluid and sera of
      women undergoing IVF were examined. Sera and follicular fluid samples from 149
      women were assayed for immunoglobulin (Ig)G and IgA antibodies to two C.
      trachomatis antigens, the major outer membrane protein (MOMP) and a recombinant
      lipopolysaccharide (rLPS) fragment. Additionally, the expression of human 60 kDa
      heat shock protein (hsp 60) in follicular fluid was determined. All cervical and
      follicular fluid samples were negative for C. trachomatis by polymerase chain
      reaction, ligase chain reaction and DNA probe. Sera from 60% of the subjects were
      positive for antichlamydial rLPS IgG; 36% were positive for anti-MOMP IgG.
      Similarly, rLPS-directed and MOMP-directed IgA were detected in sera of 34 and
      14% of the subjects respectively. IgG antibodies to MOMP and rLPS were detected
      in 42 and 41% of the follicular fluid examined respectively. Anti-MOMP IgA was
      identified in 8.7% of the follicular fluid while 27.5% were positive for anti
      rLPS IgA. Human hsp 60 expression was documented in 11.6% of the follicular fluid
      tested. IgA antibodies to both MOMP (P = 0.03) and rLPS (P = 0.02) in follicular
      fluid were associated with a failure to become pregnant after embryo transfer.
      IgG antibodies in sera and follicular fluid and IgA antibodies in sera were
      unrelated to IVF outcome. Similarly only anti-MOMP IgA (P = 0.02) and anti-rLPS
      IgA (P = 0.04) in follicular fluid were correlated with human hsp 60 expression
      in follicular fluid. The unique association between IgA antibodies to two
      chlamydial antigens in follicular fluid and both hsp 60 expression and IVF
      failure provides further support for the possibility that a persistent upper
      genital tract chlamydial infection contributes to IVF failure in some women.

PMID- 9194642
TI  - Chromosomal findings in 150 couples referred for genetic counselling prior to
      intracytoplasmic sperm injection.
AB  - A total of 150 infertile couples underwent chromosome analysis and genetic
      counselling before intracytoplasmic sperm injection (ICSI). Chromosomal
      abnormalities, including low-level sex chromosome mosaicism, were detected in 12%
      of the men and an unexpectedly high 6% of the women. Chromosomal abnormalities
      included gonosomal mosaicism in 13 cases, Robertsonian translocations in four
      males, autosomal reciprocal translocations in five cases, reciprocal
      translocation involving a sex chromosome in one case, inversions in three cases
      and a marker chromosome in one male. Chromosomal variants found in 11 women and
      13 men were not included in the above percentages. Couples with a chromosomal
      aberration in one partner received a second counselling. The different aspects of
      genetic counselling in these couples are discussed. In conclusion, we recommend
      genetic counselling and chromosomal analysis of men and women prior to ICSI
      therapy.

PMID- 9194643
TI  - Albumin gradients do not enrich Y-bearing human spermatozoa.
AB  - The aim of this study was to evaluate objectively whether or not discontinuous
      albumin gradients enrich the proportion of Y-bearing human sperm. A blinded,
      collaborative trial design was employed whereby a licensed centre prepared the
      sperm fractions using licensed procedures, coded the sperm slides and then sent
      them to an independent laboratory for determination of the X:Y ratio in each
      sperm fraction using X and Y chromosome-specific probes and double label
      fluorescence in-situ hybridization (FISH). The identification codes and FISH
      results were collated by an independent third observer. Two albumin gradient
      methods which are currently used by licensed centres for male sex pre-selection,
      protocol 3 and modified protocol 3, were tested. Essentially the same results
      were obtained for the two methods. Highly motile sperm fractions were recovered
      from the albumin gradients, and the recoveries of motile spermatozoa (1.3-8.5%)
      were within the optimal range reported to produce maximal enrichment of Y-bearing
      spermatozoa. FISH analysis, however, revealed no enrichment for Y-bearing
      spermatozoa with either method, and the overall X:Y ratios were not significantly
      different from 1.0. Some samples showed marginal enrichment of Y-bearing
      spermaotozoa, whereas others showed marginal enrichment of X-bearing
      spermaotozoa. In conclusion, this collaborative study has demonstrated that the
      protocol 3 and modified protocol 3 albumin gradient procedures do not enrich Y
      bearing spermatozoa. The clinical use of albumin gradients for male sex
      preselection should be reconsidered in the light of this and other evidence.

PMID- 9194644
TI  - Successful treatment of severe uterine synechiae with transcervical resectoscopy
      combined with laminaria tent.
AB  - Seven patients with secondary amenorrhoea were diagnosed as having severe uterine
      synechiae by hysterosalpingography (HSG) and hysteroscopy, which revealed short,
      narrow and/or scarred uterine cavities as cone or column shapes. Laminaria tents
      were used to distend the uterine cavity prior to transcervical resectoscopy to
      completely dissect the dense adhesions. A more traditional postoperative
      management included an intrauterine device, oestrogen and antibiotics.
      Transcervical resectoscopy combined with laminaria appears to be a safe and
      effective means of restoring the uterine cavity. All seven patients not only
      achieved normal menstruation but also normal uterine cavity as confirmed by
      subsequent HSG and hysteroscopy. In addition, three patients thereafter became
      pregnant, two of whom have had successful term deliveries.

PMID- 9194645
TI  - Ureteral lesion secondary to vaginal ultrasound follicular puncture for oocyte
      recovery in in-vitro fertilization.
AB  - Techniques of oocyte retrieval have progressed from laparoscopy to transvaginal
      follicular aspiration under ultrasonographic control. This highly efficient
      method, routinely used nowadays, is not free of complications. We present a case
      of a ureteral lesion secondary to vaginal ultrasound follicular puncture for
      oocyte recovery in in-vitro fertilization. Despite the surgical procedure to
      reimplant the ureter, the patient achieved a twin pregnancy which is ongoing
      uneventfully.

PMID- 9194646
TI  - The cost of infertility diagnosis and treatment in Canada in 1995.
AB  - The objectives of this study were to estimate the direct cost of infertility
      management, including diagnosis and treatment, in Canada during 1995, and the
      relative cost per live birth by treatment category. The analysis was based on the
      following estimates: the prevalence of infertility in Canada in 1995; the volume
      and distribution of infertility services; and the effectiveness and cost of
      specific infertility treatments. In 1995 there were approximately 330,000 couples
      experiencing infertility in Canada. It is estimated that <50% (150,000) sought
      medical advice or treatment during that year. A total of 13 diagnostic and
      treatment categories account for nearly all of the treatments received, and these
      categories form the treatment model. The cost of treatment per live birth ranges
      from Cdn$650 for clomiphene treatment of unexplained infertility to Cdn$41,000
      for in-vitro fertilization. For a hypothetical group of 100 couples, the annual
      cost of diagnosis and treatment would be Cdn$77,000 and Cdn$200,000 respectively
      for a total of Cdn$277,000, or an average of Cdn$2770 per couple. After 1 year of
      treatment, it is expected that 26 of these 100 couples would achieve a live
      birth. The total annual cost of infertility management in Canada, estimated to be
      approximately Cdn$415 million, is 0.6% of the annual cost of health care.

PMID- 9194647
TI  - Endometrial carcinoma in a young patient with polycystic ovarian syndrome: first
      suspected at time of embryo transfer.
AB  - Adenocarcinoma of the endometrium is a rare condition in women under 40 years of
      age. However, patients with anovulatory polycystic ovarian syndrome are at risk
      of developing endometrial carcinoma due to the unopposed and prolonged effect of
      oestrogen on the endometrium. This case report discusses the dilemma of various
      treatment options for early disease in such patients.

PMID- 9194648
TI  - Potentially important variables identified by transvaginal ultrasound-guided
      embryo transfer.
AB  - Transvaginal ultrasound-guided embryo transfer was performed on 121 consecutive
      patients. Observation was made of guiding cannula and transfer catheter placement
      in relation to the endometrial surface and uterine fundus during embryo transfer.
      The position and movement of a transfer-associated air bubble and the impact of
      subendometrial myometrial contraction leading to endometrial movement was
      observed. Results indicate that tactile assessment of embryo transfer catheter
      placement is unreliable: in 17.4% of transfers the outer guiding catheter
      inadvertently abutted the fundal endometrium. The outer guiding cannula indented
      the endometrium in 24.8% and the transfer catheter embedded in the endometrium in
      33.1%. Unavoidable sub-endometrial transfers occurred in 22.3% of transfers.
      Ultrasound-guided transfer avoided accidental tubal transfer in 7.4% of
      transfers. Transfer catheter withdrawal did not significantly affect embryo
      transfer-associated air bubble position. Endometrial movement due to sub
      endometrial myometrial contraction was obvious in 36.4% of cases, with active
      motion of the transfer-associated air bubble occurring in 28.1%. Pregnancies
      occurred in 45.5% of transfers with endometrial movement compared to 15.6% (P <
      0.001) without.

PMID- 9194649
TI  - Pharmacokinetics and pharmacodynamics of 7alpha-methyl-19-nortestosterone after
      intramuscular administration in healthy men.
AB  - 7alpha-Methyl-19-nortestosterone (MENT) is a potent synthetic androgen that is
      resistant to 5alpha-reductases and therefore less prone to over-stimulate the
      prostate. It is a good candidate for implant administration in long-term androgen
      replacement therapy for hypogonadal men or as part of a male contraceptive
      system. To investigate the pharmacokinetics of MENT after i.m. administration,
      single i.m. injections of 2, 4 or 8 mg of micronized MENT were given in aqueous
      suspension to 18 healthy men in two clinics. Blood was sampled frequently for 8 h
      and 1, 2, 3, 4 and 9 days after the injections. Serum MENT concentrations were
      determined by radioimmunoassay. Peak MENT concentrations were dose-dependent and
      were reached about 1-2 h after the injections. Doubling the dose of MENT resulted
      in an increase of 60% in peak serum MENT concentrations. The mean +/- SE
      clearance rate was 1790 +/- 140 l/day. The antigonadotrophic activity of MENT was
      investigated by giving six consecutive daily i.m. injections of 1, 2 or 4 mg of
      MENT to 24 healthy men in two clinics. Blood was sampled before each injection
      and up to 24 days after the last injection. Serum testosterone and gonadotrophin
      concentrations (determined by radioimmunoassay and fluoroimmunoassay
      respectively) decreased in a dose-dependent and statistically significant manner.
      The highest dose caused a 74% fall in testosterone, a 70% fall in luteinizing
      hormone, and a 57% fall in follicle stimulating hormone concentrations. MENT
      injections did not cause any side-effects. The results show that MENT is a potent
      antigonadotrophic agent in men.

PMID- 9194650
TI  - Inconstant ascending testis as a potential risk factor for spermatogenesis in
      infertile men with no history of cryptorchism.
AB  - The usual testicular location, either low or high in the scrotum, as well as
      testis ascent into suprascrotal position at least once a week from a usually
      scrotal position reported by the patient to occur spontaneously and regularly,
      were recorded in 85 fertile and 1014 infertile men, including 95 with a history
      of cryptorchism. The frequency of at least one testis being in a high scrotal
      location was similar in fertile (16.5%) and non-cryptorchid infertile (17%) men
      but higher in previously cryptorchid infertile men (27.2%), a difference probably
      due to cryptorchism. Testicular ascent was more frequent when scrotal location
      was high rather than low. An ascending testis was encountered more frequently in
      previously cryptorchid (30.4%) than in non-cryptorchid infertile men without any
      history of cryptorchism (18.3%) or in fertile men (11.8%). Moreover, in infertile
      men, spermatogenesis was more depressed in cases of testicular ascent than when
      both testes were never ascending, independently of a varicocele. Testis ascent
      could be a risk factor for spermatogenesis in infertile men without any history
      of maldescended testicle.

PMID- 9194651
TI  - Subcutaneous self-administration of highly purified follicle stimulating hormone
      and human chorionic gonadotrophin for the treatment of male hypogonadotrophic
      hypogonadism. Spanish Collaborative Group on Male Hypogonadotropic Hypogonadism.
AB  - The efficacy and safety of highly purified follicle stimulating hormone (FSH)
      associated with human chorionic gonadotrophin (HCG) was studied in 60 men with
      hypogonadotrophic hypogonadism. Of these men, 16 suffered from Kallmann's
      syndrome, 19 from idiopathic hypogonadotrophic hypogonadism and 25 from
      hypopituitarism. Basal testosterone concentrations were found to be far below the
      normal range. At baseline, 26 patients were able to ejaculate and all of them
      showed azoospermia, while the remaining patients were aspermic. All patients self
      administered s.c. injections of FSH (150 IU x three/week) and HCG (2500 IU x
      two/week) for at least 6 months and underwent periodic assessments of testicular
      function. Testosterone concentrations increased rapidly during treatment and all
      but one patient reached normal values. Testicular volume showed a sustained
      increase reaching almost 3-fold its baseline value. At the end of treatment, 48
      patients (80.0%) had achieved a positive sperm count. The maximum sperm
      concentration during treatment was 24.5 +/- 8.1 x 10(6)/ml (mean +/- SEM). The
      median time to induce spermatogenesis was 5 months. Eleven patients reported
      adverse events, generally not related to treatment. Three patients experienced
      gynaecomastia. No local reactions at injection site were observed. In conclusion,
      the s.c. self-administration of highly purified FSH + HCG was well tolerated and
      effective in stimulating spermatogenesis and steroidogenesis in these patients.

PMID- 9194652
TI  - Semen parameters in a fertile versus subfertile population: a need for change in
      the interpretation of semen testing.
AB  - This prospectively designed study was conducted to compare a fertile and a
      subfertile population so as to define normal values for different semen
      parameters. Semen analyses were performed according to the World Health
      Organization (WHO) guidelines, except for sperm morphology (strict criteria). In
      the fertile population (n = 144), all patients had recently achieved pregnancy,
      within 12 months of unprotected coitus. As subfertile controls we examined semen
      samples from 143 consecutive men attending our infertility clinic during the same
      study period. Couples with tubal factor infertility and/or ovulatory disorders
      were excluded from our study. Using receiver operating characteristic (ROC) curve
      analysis we determined the diagnostic potential and cut-off values for single and
      combined sperm parameters. Sperm morphology scored best, with a value of 78%
      (area under the ROC curve). Summary statistics showed a shift towards abnormality
      for most semen parameters in the subfertile population. Using the 10th percentile
      of the fertile population as the cut-off value, the following results were
      obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility
      and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x
      10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different
      from those described in the WHO guidelines. Routine bacterial and non-bacterial
      cultures turned out to be of little prognostic value.

PMID- 9194653
TI  - Cryopreservation of single human spermatozoa.
AB  - A procedure is described that allows cryopreservation and efficient post-thaw
      recovery of either a single or a small group of human spermatozoa. This is
      achieved by injecting them into cell-free human, mouse or hamster zonae
      pellucidae before the addition of cryoprotectant. The method involves a
      combination of physical micromanipulation procedures and glycerol-mediated
      cryoprotection. Zonae were tracked by positioning them in straws between two
      small air bubbles prior to freezing. Spermatozoa from poor specimens were
      cryopreserved and their fertilizing ability after thawing was compared with that
      of fresh spermatozoa from fertile men. Human eggs used for fertilization testing
      were either 1 day old or in-vitro matured. Only 2% of the frozen zonae were lost
      and >75% of spermatozoa cryopreserved in this manner were recovered and prepared
      for intracytoplasmic sperm injection. The feasibility of cryopreserving a single
      spermatozoon was assessed. Fifteen motile spermatozoa were frozen in 15 zonae, of
      which 14 were recovered after thawing. Ten were injected into spare eggs, of
      which eight became fertilized. Spermatozoa recovered mechanically from human
      zonae fertilized the same proportion of oocytes as fresh fertile control
      spermatozoa. The recovery and fertilization rates with spermatozoa frozen in
      animal zonae were 87 and 78% respectively. The fertilization rate was marginally
      higher (P < 0.05) than that for spermatozoa frozen in human zonae, perhaps
      because the latter may have acrosome reacted more frequently. The zona pellucida
      appears to be an ideally suited sterile vehicle for storage of single
      spermatozoa.

PMID- 9194654
TI  - No evidence of deteriorating semen quality among men in infertile relationships
      during the last decade: a study of males from Southern Sweden.
AB  - The aim of this study was to investigate whether the quality of semen has
      deteriorated during the last decade. Laboratory records containing semen analysis
      results were reviewed. The records, arranged according to date of birth, are kept
      in shelves. Every fifth record for analyses performed between 1985 and 1995, and
      only those of men in infertile relationships, were included. The data were
      abstracted in a data base, and time-related changes in semen characteristics were
      studied using linear regression analyses. During the study period, there was a
      slight, but significant increase in sperm concentration, percentage of motile
      spermatozoa, percentage of spermatozoa with normal morphology, and the base-value
      of the penetration test. The seminal volumes decreased slightly, but
      significantly. Sperm characteristics were not associated with age or date of
      birth of the men. In conclusion, these data show no evidence of deterioration in
      sperm quality during the last decade among men in infertile relationships.

PMID- 9194655
TI  - Quantitative observations of flagellar motility of capacitating human
      spermatozoa.
AB  - For technical reasons sperm head movement is assessed in kinematic analysis,
      while flagellar movement is the determining factor of head movement, not vice
      versa. It follows then that the development of new kinematic values to describe
      the movement of capacitating human spermatozoa should include the analysis of
      their flagellar movement. The aim of this study was to establish quantitative
      differences between flagellar movement patterns of hyperactivated and non
      hyperactivated spermatozoa which could then be used in the evaluation of new
      centroid-based kinematic values. Spermatozoa were prepared by swim-up from semen
      into culture medium supplemented with 30 mg/ml human serum albumin. Sperm
      movement was recorded in 50 microm-deep chambers using a 200 Hz video system.
      Sperm movement was classified based on flagellar movement, with 24 non
      hyperactivated and 26 hyperactivated spermatozoa included in the study. Flagellar
      analysis was performed using both a semi-automated analysis system (SIAM FLAG; 30
      images at 200 Hz) and manual methods (100 Hz). Hyperactivated spermatozoa had
      significantly larger flagellar beat angles (> or = 87 degrees) and significantly
      lower flagellar beat frequencies (< or = 29.4 Hz) than non-hyperactivated human
      spermatozoa. In addition, the flagellar wave amplitude was significantly greater
      and the bend diameter significantly smaller for hyperactivated spermatozoa in the
      proximal region of the flagellum (up to 20 microm from the head-midpiece
      junction). The velocity of the hyperactivated wave was low in this region,
      although it was significantly slower than the non-hyperactivated wave in all
      regions of the sperm tail.

PMID- 9194656
TI  - Utility of percutaneous epididymal sperm aspiration in situations of unexpected
      obstructive azoospermia.
AB  - Surgical sperm retrieval through percutaneous epididymal aspiration was used to
      manage effectively unexpected obstructive azoospermia on the day of oocyte
      retrieval.

PMID- 9194657
TI  - Results of a questionnaire on sperm morphology assessment.
AB  - This survey describes the results of a questionnaire on the methodology of sperm
      morphology assessment. A questionnaire form was sent to 410 fertility centres. A
      total of 170 answer forms (41.5%) from 40 different countries was evaluated. Most
      responding centres (147 or 86.5%) treat more than 200 new couples per year.
      According to our results, a wide and complex variation in different methods of
      sperm preparation, staining procedures and classification systems is observed
      world wide. WHO recommendations for sperm preparation seem to be poorly followed.
      Only 86 centres (50.6%) reported the use of a single approach to both semen
      preparation and sperm morphology evaluation. Our results indicate an urgent need
      for standardization and consensus on sperm morphology methodology to regain the
      power of this important sperm parameter.

PMID- 9194658
TI  - Sertoli-Leydig cell tumour in an infertile patient after stimulated ovulation.
AB  - A 36 year-old infertile female developed a stage IV (FIGO) ovarian carcinoma
      consisting of a poorly differentiated Sertoli-Leydig cell tumour after receiving
      one course of ovulation induction with follicle stimulating hormone (FSH), human
      menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) followed
      by gonadotrophin-releasing hormone analogue (GnRHa). The patient died of liver
      metastasis and hepatic failure 4 1/2 months after first diagnosis, despite
      aggressive treatment consisting of debulking surgery and aggressive adjuvant
      chemotherapy.

PMID- 9194659
TI  - Does corpus luteum locally affect follicular growth negatively?
AB  - In this study bilateral ovarian follicular growth during the luteal phase was
      investigated in relation to the ovary where ovulation occurred. The diameter of
      the largest follicle in the contralateral ovary without corpus luteum and in the
      ipsilateral ovary with corpus luteum was measured using vaginosonography in a
      total of 66 natural cycles of 27 normally cycling women undergoing treatment with
      intrauterine insemination (IUI). None of the women received ovarian stimulation
      or luteal support. Follicles from 2 to 11 mm in diameter were measured in early
      luteal phase (day +1 to +4), mid-luteal phase (day +5 to +9) and late luteal
      phase (day +10 onwards). The mean diameters of the largest follicle in the
      contralateral ovary without corpus luteum during the early, mid- and late luteal
      phases were 6.81 +/- 1.33 (mean +/- SD), 6.14 +/- 1.29 and 5.71 +/- 1.17 mm
      respectively, while those of the ipsilateral ovary with corpus luteum were 6.48
      +/- 1.40, 5.65 +/- 1.47 and 4.98 +/- 1.19 mm respectively. While there was no
      significant difference during the early luteal phase, the mean diameter of the
      largest follicle in the ipsilateral ovary with corpus luteum was significantly
      smaller than that of the contralateral ovary without corpus luteum during the mid
      luteal phase (P < 0.004) and the late luteal phase (P < 0.0005). These results
      indicate that the corpus luteum locally affects neighbouring follicular growth
      negatively during the luteal phase of the menstrual cycle, with the most
      pronounced effect expressed in the mid- and late luteal phases.

PMID- 9194660
TI  - Follicular density in ovarian biopsy of infertile women: a novel method to assess
      ovarian reserve.
AB  - The ageing ovary appears to be characterized by depletion of primordial
      follicles. The relationship between infertility and the number of follicles in
      the ovarian cortex is not known. Moreover, there are no accurate markers or
      clinical methods to predict the decline in ovarian reserve. This study
      investigates the correlation between early follicular follicle stimulating
      hormone, ovarian size and follicular density in 60 infertile women aged 19-45
      years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while
      performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or
      myomectomy (n = 32). The median number of follicles was similar in tubal and
      unexplained infertility patients (9.5 versus 5.5). Increasing age showed a
      significant negative correlation with follicular density and ovarian volume (r = 
      0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years
      of age the ovarian volume showed a strong correlation with follicular density (r
      = 0.71, P < 0.0001). Our results indicate that infertile women in their late
      thirties and over have a decreased ovarian reserve which could possibly be
      predicted by ovarian volume measurement. Ovarian biopsy may have a place as part
      of infertility evaluation in older women.

PMID- 9194661
TI  - Extracellular matrix improves survival of both stored and fresh human primordial
      and primary ovarian follicles in long-term culture.
AB  - Ovarian cortical tissue was obtained during gynaecological operations by biopsy
      or after oophorectomy from 20 women aged 25-42 years. It was placed in organ
      culture, either fresh or following thawing after cryopreservation, for 1-4
      months. The tissue was cut in slices 0.1-0.3 mm in diameter and transferred to 12
      mm inserts in 24-well culture plates. These slices were cultured for 4-21 days in
      either alpha minimum essential medium (alpha-MEM) or Earle's balanced salt
      solution with added pyruvate. Both media were supplemented with 10% human serum,
      insulin, gonadotrophins and antibiotics. Half of the inserts were precoated with
      extracellular matrix (Matrigel). Histological samples revealed that there were
      viable, non-atretic, primordial, primary and secondary follicles in all the
      cultures. Mitoses were seen in the granulosa cells of the secondary follicles.
      Although the proportion of atretic follicles increased during culture, non
      atretic follicles were still present after 21 days. After 4-11 days the
      proportion of viable follicles was significantly higher when cultured in Earle's
      solution supplemented with pyruvate, than when cultured in MEM (77 versus 38%, P
      < 0.001). In cultures with extracellular matrix the proportion of viable
      follicles was significantly higher after 10-15 days than it was without matrix
      (85 versus 19%, P < 0.001). Culture after thawing frozen ovarian tissue did not
      affect the density or the proportion of the viable follicles. Two-thirds of
      follicles in cryopreserved tissue were viable after 10-15 days in culture. The
      results indicate that it is possible to culture human primary and primordial
      follicles in vitro, and follicles in cryopreserved tissue are viable.

PMID- 9194662
TI  - Compartmentalization of human chorionic gonadotrophin sensitivity and luteinizing
      hormone receptor mRNA in different subtypes of the human corpus luteum.
AB  - The relationship was investigated between different ultrasonographically defined
      subtypes of the human corpus luteum and progesterone production. Twenty-one women
      in the mid-luteal phase who underwent laparotomy for benign uterine conditions
      volunteered for this study. The corpus luteum was identified by preoperative
      ultrasound and classified into four types according to earlier established
      criteria, where types a and c were centrally hypoechoic, types b and d were
      centrally echogenic, types a and b had thin surrounding 'walls' (<3 mm) and types
      c and d had thick walls (<3 mm). After luteectomy, the theca externa capsule was
      removed and tissue from directly beneath the surface ('peripheral region') and
      the layer immediately beneath ('inner region') minced into 4-6 mg pieces.
      Following preincubation, pieces were incubated for 3 h at 37 degrees C in HEPES
      minimal essential medium buffer with or without human chorionic gonadotrophin
      (HCG; 10 IU/ml), and subsequently progesterone accumulation in the medium was
      determined by radioimmunoassay. The highest progesterone production was
      consistently seen in the peripheral region. Type a had a significantly (P > 0.01)
      lower progesterone production (3.2 +/- 1.5 nmol/g tissue wet weight, mean +/-
      SEM, n = 4) than that of types b, c and d (17.7 +/- 3.5 nmol/g tissue wet weight,
      n = 9). All types responded to HCG with an almost two-fold increase in
      progesterone production. However, the maximal progesterone produced following
      stimulation by HCG in the type a corpus luteum was <50% of the basal
      (unstimulated) progesterone synthesis of any other type of corpus luteum. Using
      in-situ hybridization, with a primate RNA probe complementary to the region
      coding the extracellular part of the luteinizing hormone (LH) receptor, a highly
      localized expression of LH receptor mRNA to the peripheral region was found.
      Negligible or low levels of expression were found in the theca externa capsule
      and the inner region. No obvious correlations between the different subtypes of
      corpora lutea and LH receptor mRNA expression were seen. Thus, the
      ultrasonographic detection of a thin-walled and centrally hypoechoic corpus
      luteum correlates well with reduced progesterone secretion. The underlying
      cellular mechanism does not appear to involve a diminished sensitivity to the
      gonadotrophic stimulation by LH or HCG.

PMID- 9194663
TI  - Interest of co-cultures for embryos obtained by in-vitro fertilization: a French
      collaborative study.
AB  - Co-cultures of human embryos, particularly with Vero cells, are used by several
      French groups, mainly in cases of successive failures of implantation. In most
      cases co-culture is continued until the blastocyst stage, expanded if possible. A
      total of 1603 co-cultures have been performed by 11 groups over a 2-year period.
      Of these, 41.8% of cleaved eggs (day 2) reached the blastocyst stage at day 5 or
      day 6. The mean pregnancy rate and implantation rate per transfer were 32.9 and
      24.8% respectively, which represented a significant improvement compared to the
      transfer of 2 day old embryos. The rate of multiple pregnancies remained high
      (29.1%), which implies that there should be transfer of not more than two
      blastocysts. The rate of anomalies perceived at birth or in utero was not
      different from the rate observed in the general population, taking account of the
      maternal age.

PMID- 9194664
TI  - The developmental potential of the human oocyte is related to the dissolved
      oxygen content of follicular fluid: association with vascular endothelial growth
      factor levels and perifollicular blood flow characteristics.
AB  - Regardless of whether fertilization occurs in vivo or in vitro, a large
      proportion of human embryos do not develop progressively through the pre
      implantation stages or arrest development after implantation. This study examined
      the association between the chromosomal/spindle normality of the mature human
      oocyte and the dissolved oxygen content, vascular endothelial growth factor
      concentration (VEGF) and perifollicular blood flow characteristics of the
      corresponding ovarian follicles. Findings from >1000 samples of follicular fluid
      show that developmentally significant differences in dissolved oxygen content
      occur in follicular fluids aspirated from follicles of equivalent size and
      ultrasonographic appearance. Oocytes from severely hypoxic follicles were
      associated with high frequencies of abnormalities in the organization of the
      chromosomes on the metaphase spindle that could lead to segregation disorders and
      catastrophic mosaicisms in the early embryo. Oocytes with cytoplasmic defects and
      cleavage stage embryos with multinucleated blastomeres are derived predominantly
      from severely hypoxic follicles. VEGF measurements of follicular fluid and colour
      pulsed Doppler ultrasonographic analysis of follicle-specific blood flow
      characteristics indicated a potentially important role for this factor both in
      perifollicular angiogenesis and in the regulation of intrafollicular oxygen
      levels. The results are discussed with respect to how severe intrafollicular
      hypoxia may influence the normality of chromosomal organization and segregation
      in the oocyte, and whether detailed pulsed Doppler analysis of individual pre
      ovulatory follicles may provide an indirect indication of the 'health' of the
      follicle and possibly the developmental competence of the corresponding oocyte.

PMID- 9194665
TI  - Birth from cryopreserved embryos following in-vitro maturation of oocytes and
      intracytoplasmic sperm injection.
AB  - This case report describes the birth of a baby following the transfer of
      cryopreserved embryos generated from intracytoplasmic sperm injection (ICSI)
      carried out on the second day after oocyte pick-up of in-vitro-matured metaphase
      I and germinal vesicle stage oocytes. The couple had a history of three failed
      intrauterine insemination attempts and reduced fertilization rates in two
      previous in-vitro fertilization (IVF) cycles. In the IVF-ICSI treatment cycle,
      6/11 mature oocytes became fertilized following ICSI on the first day. However,
      the patient failed to conceive following the transfer of three embryos. Five
      oocytes were immature (two at metaphase I stage and three with a germinal
      vesicle) and these were cultured overnight. All had extruded a polar body by the
      following day and ICSI was therefore performed; four oocytes became fertilized,
      and were cryopreserved at the pronulear stage in propanediol. In the next
      treatment cycle, transfer of frozen embryos was planned. The pronuclear zygotes
      were thawed and cultured for 24 h prior to the transfer of two embryos in a cycle
      stimulated with low doses of follicle stimulating hormone. This resulted in a
      pregnancy and the delivery of a healthy baby boy. In-vitro maturation of
      metaphase I and germinal vesicle oocytes which are routinely collected in IVF
      ICSI cycles, followed by second day ICSI fertilization, may provide a valuable
      source of embryos for infertile couples.

PMID- 9194666
TI  - Triploidy caused by endoreduplication in a human zygote obtained after in-vitro
      fertilization.
AB  - Cytogenetic analysis of a presumably tripronuclear zygote revealed that triploidy
      was caused by an endoreduplicated 46,XX complement. The remaining chromosomes
      yielded a hyperhaploid karyotype of 28,Y, +2, +3C, +D. The origin of this
      chromosomal composition is obscure. Besides endoreduplication in a normal 23,X
      oocyte pronucleus and fertilization by a normal 23,Y spermatozoon, an additional
      female pronucleus might have been formed due to an irregular chromosome
      distribution during second meiotic division. On the other hand, penetration by a
      hyperhaploid spermatozoon cannot be excluded with certainty.

PMID- 9194668
TI  - Teratozoospermia influences fertilization rate in vitro but not embryo quality.
AB  - The purpose of this study was to retrospectively compare the overall results and
      embryo quality in 102 cycles of in-vitro fertilization (IVF)-embryo transfer
      using normal frozen donor semen (group D) and 94 cycles of IVF-embryo transfer
      using husbands' teratozoospermic sperm (group T). Donor semen was purchased from
      men with proven fertility and normal semen parameters. Teratozoospermia was
      defined in group T as the presence of <20% of normal spermatozoa in semen on the
      day of oocyte retrieval. Exclusion criteria were a sperm count <10 x 10(6)/ml or
      with <10% progressive motility. Fertilization rate, transfer rate and number of
      transferred embryos per cycle were significantly lower in the teratozoospermic
      group (45 vs 72%, 66 vs 96%, 1.7 vs 2.9%, respectively). Pregnancy rate per cycle
      was also lower, but not significantly (18 vs 28%). However, pregnancy rate per
      transfer, implantation rate per transferred embryo and take home baby rate were
      comparable (27 vs 30%, 15 vs 15%, 21 vs 24%, respectively). Similarly, embryo
      quality in terms of number of embryos displaying fragmentations or irregular
      cells, cleavage stages and embryo scores were comparable. When group T was
      divided into two subgroups according to sperm count (group T1: sperm count = 10
      20 x 10(6)/ml; group T2: sperm count >20 x 10(6)/ml), there was no difference
      between them with regard to fertilization rate, pregnancy rate or embryo quality.
      This study confirms low pregnancy rate per cycle in IVF-embryo transfer using
      teratozoospermic semen, but demonstrates for the first time that embryo quality
      and viability are not impaired. It is proposed that the poor pregnancy rate per
      cycle obtained is due only to the poor fertilization rate, and to the subsequent
      limited choice of embryos to be transferred.

PMID- 9194667
TI  - Sperm-induced oocyte activation in the rhesus monkey: nuclear and cytoplasmic
      changes following intracytoplasmic sperm injection.
AB  - Intracytoplasmic sperm injection (ICSI) has increased the potential of the
      assisted reproductive technologies to propagate mammalian species and has
      provided an opportunity for research into cell cycle control and the mechanisms
      involved in sperm-induced oocyte activation. We have investigated the efficacy of
      ICSI in the rhesus monkey, the mechanism of fertilization following sperm
      injection and the cytoskeletal rearrangement that occurs upon oocyte activation.
      These studies were conducted on mature, and to a lesser extent, immature oocytes.
      Ejaculated spermatozoa, washed, capacitated and activated before immobilization,
      were injected into oocytes using conventional ICSI methodology. Sperm injection
      into mature oocytes induced oocyte activation (19/22; 86%) and pronuclear
      formation. In contrast, sham-injected oocytes did not activate readily (2/16;
      13%). To localize oocyte activation factor(s), spermatozoa were separated
      mechanically into heads and tails which were then injected individually into
      mature oocytes. Activation occurred in 87% (20/23) of oocytes receiving heads.
      After tail injection, a single microtubule aster was nucleated and one pronucleus
      (PN) was seen in four of 21 oocytes. Intracytoplasmic injection of sperm extract
      (SE) resulted in oocyte activation at a significantly higher rate than occurred
      following sham injection (76 versus 13%). Sperm-induced oocyte activation was
      also evaluated in immature metaphase (MI) oocytes; activation occurred in 46%
      (12/26) of cases; however, only 8% of the activated oocytes exhibited 2 PN.
      Finally, beta-tubulin localization in untreated and taxol-treated oocytes was
      established as a marker for cytoplasmic changes associated with oocyte
      activation. These results are consistent with the hypothesis that spermatozoa
      contain an oocyte activating factor(s) which is primarily localized in the sperm
      head. Moreover, an activation response is limited to mature oocytes and is
      accompanied by cytoskeletal changes analogous to those seen following
      conventional fertilization.

PMID- 9194669
TI  - Targeted drug delivery in gynaecology: the first uterine pass effect.
AB  - The objective was to verify the hypothesis of a 'first uterine pass effect' or
      direct preferential vagina-to-uterus transport, suggested by the evidence of
      higher than expected uterine tissue concentrations after vaginal administration
      of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of
      tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal
      tissue remaining attached to the cervix after hysterectomy. At the end of the
      perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples
      of uterine tissue. Tritiated water and [14C]dextran were tested to determine the
      extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of
      uterine tissue exposed only to [3H]progesterone were prepared for
      autoradiography. By 4-5 h after application progesterone had diffused to the
      entire uterus and had reached a steady state; 4 h after application, progesterone
      concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and
      myometrial tissue respectively. Endometrial extraction of progesterone was higher
      when the experiment was performed on uteri obtained during the luteal phase (280
      +/- 156 ng/100 mg of endometrial tissue) than those removed during the
      proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial
      tissue). These data demonstrate that a 'first uterine pass effect' occurs when
      drugs are delivered vaginally, thereby providing an explanation for the
      unexpectedly high uterine concentrations relative to the low serum concentration
      observed after vaginal administration. Hence, the vaginal route permits targeted
      drug delivery to the uterus, thereby maximizing the desired effects while
      minimizing the potential for adverse systemic effects.

PMID- 9194670
TI  - The role of hyaluronic acid as a mediator and regulator of cervical ripening.
AB  - During pregnancy, hyaluronic acid (HA) concentration in the human cervix is very
      low, but increases rapidly at the onset of labour. HA has a high affinity for
      water molecules and hence can maintain tissue hydration. HA can stimulate
      collagenase production in rabbit cervix, and also stimulates migration and
      function of polymorphonuclear leukocytes in the tissues. It is an endogenous
      regulator of interleukin-1 (IL-1). We hypothesized that HA plays an essential
      role during cervical ripening. The effect of exogenous application of HA (20 mg)
      on non-pregnant and pregnant (day 23) rabbit cervices was compared with controls.
      HA induced cervical ripening in both pregnant and non-pregnant animals, and
      cervical water content was significantly increased. Tissue collagen was markedly
      decreased. The localization and distribution of HA and HA receptor CD44 was
      determined in non-pregnant and pregnant human cervical connective tissue using
      biotinylated HA binding protein and CD44 monoclonal antibodies. Both were widely
      distributed in the connective tissues, especially around the blood vessels and
      cervical glands. The effect of IL-8 (50, 100, 150 and 200 ng/ml) on HA production
      and hyaluronidase (HAase) activity was investigated in cultures of lower uterine
      segment collected during elective Caesarean sections. HA production was
      stimulated in a dose-dependent manner; there was no effect on hyaluronidase
      activity. HA administration (0.5, 1 and 2 mg/ml) stimulated the activities of
      collagenase and gelatinase together with IL-8 production in the culture
      supernatants. Thus HA may play an important role in cervical ripening, being
      involved in the regulation of cervical tissue water content, collagenolytic
      enzymes and cytokines.

PMID- 9194671
TI  - Source of circulating levels of inhibin A, pro alpha C-containing inhibins and
      activin A in early pregnancy.
AB  - It is now established that the glycoprotein hormone inhibin is produced by
      primate granulosa cells, corpus luteum and trophoblast of human placenta. This
      study was designed to investigate the major source of inhibins and activin A in
      early pregnancy using a novel panel of assays with high specificity and
      sensitivity. A total of 12 women (aged 20-35 years) with singleton pregnancy
      undergoing first trimester (group 1: 6-8; group 2: 8-10; group 3: 10-12 weeks of
      gestation) termination of pregnancy (TOP) was recruited for the study. Blood
      samples were taken before TOP, every 15 min for the first hour and hourly for the
      next 3 h after TOP (total of 4 h of measurements). Circulating concentrations of
      inhibin A, pro alpha C, activin A, human chorionic gonadotrophin (HCG),
      oestradiol and progesterone were higher in early pregnancy than at any stage of
      the menstrual cycle. Peripheral concentrations of inhibin A and activin A were
      significantly decreased within the first hour in all three groups and gradually
      decreased to even lower concentrations within the study period. Pro alpha C
      concentrations decreased within the first hour and then remained unaltered during
      the next 3 h. Similarly, HCG, oestradiol and progesterone concentrations in
      circulation decreased substantially within 4 h of TOP. Correlation analyses
      showed a significant positive correlation (P < 0.001) between inhibin A, activin
      A, HCG, and oestradiol concentrations throughout the study period. In summary,
      this study shows that the feto-placental unit is the major source of increased
      circulating concentrations of inhibin A in early pregnancy. Activin A is produced
      by the feto-placental unit and the corpus luteum. Pro alpha C-containing inhibins
      are mainly secreted by the corpus luteum in early pregnancy.

PMID- 9194672
TI  - First-trimester repeated abortion is not associated with activated protein C
      resistance.
AB  - The present study was undertaken to investigate the possible association between
      activated protein C resistance and first-trimester repeated abortion. Fifty-five
      consecutive patients with unexplained first-trimester repeated abortion and 50
      healthy control women having at least one child but no previous abortion were
      included. Activated protein C resistance was measured in all subjects and factor
      V Leiden genotype testing was performed in those individuals with phenotypic
      activated protein C resistance. One patient with first-trimester repeated
      abortion and one control subject had phenotypic activated protein C resistance.
      Genotype analysis confirmed that both subjects were heterozygous for factor V
      Leiden. Our results indicate that first-trimester repeated abortion is not
      associated with activated protein C resistance. Factor V Leiden screening in
      first-trimester repeated abortion is not warranted.

PMID- 9194673
TI  - Spontaneous heterotopic pregnancy presenting with tubal rupture.
AB  - We present the case of a woman who sought pregnancy termination but who, in the
      interval between consultation and surgical termination, presented with clinical
      signs of a ruptured ectopic pregnancy. This was managed as such, but post
      operative follow-up soon revealed that she also carried a viable intrauterine
      pregnancy.

PMID- 9194674
TI  - The role of laparoscopy in the diagnosis and management of heterotopic
      pregnancies.
AB  - The object of this report is to discuss diagnosis and treatment of heterotopic
      pregnancies. Thirteen consecutive cases referred to our institution are reviewed.
      In 54% of cases the heterotopic pregnancy was asymptomatic. The ectopic pregnancy
      was visualized prior to surgery in 69% of the cases. The treatment was surgical
      in every case and performed laparoscopically in 77% of cases. Ten patients
      underwent salpingectomy and three salpingostomy. In all, 60% of intrauterine
      pregnancies that were viable at the time of diagnosis of the heterotopic
      pregnancy had a favourable outcome. Diagnosis of heterotopic pregnancy is
      difficult. Laparoscopy allows both diagnosis and treatment, and the outcome of
      the intrauterine pregnancy is comparable to that obtained with laparotomy.

PMID- 9194675
TI  - A case of pregnancy in a woman with cloacal dysgenesis and a rudimentary uterine
      horn.
AB  - Cloacal dysgenesis is frequently associated with uterine anomalies. We report a
      case of pregnancy which resulted in an abortion in a woman with a persistent
      cloaca. Presumptive diagnosis before operation was ectopic pregnancy of the left
      tube. Postoperatively, the site of implantation of the conceptus was found to be
      the cavity of a unicornuate uterus in association with a rudimentary horn, the
      presence of which misled us to diagnose an ectopic pregnancy.

PMID- 9194676
TI  - Spontaneous abortion and psychosomatics. A prospective study on the impact of
      psychological factors as a cause for recurrent spontaneous abortion.
AB  - A group of 36 patients who had had at least two consecutive spontaneous abortions
      and who desired to have children was subjected to a psychosomatic investigation
      before a biomedical diagnostic screening programme was started. A semi-structured
      interview regarding sociodemographic data, current relationship, social support,
      education, occupation and medical anamnesis was carried out. In addition, all
      women completed four standardized questionnaires on the topics of anxiety,
      somatization disorder, life satisfaction and depression. A control group of 36
      women, matched for age and occupation, was subjected to the same psychosomatic
      investigation. The findings of the diagnostic screening programme showed that 16
      women had abortions because of physical abnormality, and 15 women had no
      physically confirmed cause (in five women, the investigations were not
      completed). Following recurrent spontaneous abortion, 18 women had a successful
      pregnancy within 2 years, and 18 women were still childless. The comparison
      between patients and the control group revealed that patients with recurrent
      abortion were significantly more satisfied with their life quality regarding
      leisure time, financial situation and occupation. No significant differences were
      observed in any other variables. Patients who suffered spontaneous abortions due
      to a physical disorder showed partner relationship of longer duration, and more
      frequent miscarriages. Women with successful pregnancy within 2 years after
      recurrent miscarriage were significantly younger and had fewer physically related
      abortions compared with women who remained childless. In summary, psychological
      factors seem to be of subordinate importance as a cause for recurrent spontaneous
      abortion. Moreover, physical abnormalities in the reproductive system have a
      predominant impact on the prediction of a future successful pregnancy.

PMID- 9194677
TI  - Establishment of an optimal hypo-osmotic swelling test by examining single
      spermatozoa in four different hypo-osmotic solutions.
AB  - In order to find an optimal hypo-osmotic swelling test (HOST) and to identify
      viable sperm cells from patients with asthenozoospermia for intracytoplasmic
      sperm injection (ICSI), we tested single motile and non-motile spermatozoa in
      four hypo-osmotic solutions by micromanipulation. The four solutions were: A,
      H2O; B, 50 mOsm NaCl; C, 150 mOsm NaCl and D, 150 mOsm sodium citrate and
      fructose. Eosin Y staining was then carried out for evaluation of viability of
      the spermatozoa after HOST. Using motile spermatozoa, no statistical difference
      was found in HOST-positive spermatozoa between these four solutions. There were
      more viable sperm cells after HOST in solutions C and D, as noted by Eosin Y
      staining. After non-motile spermatozoa were incubated for 1 min in the four
      solutions, HOST with solution C gave the best results for identification of
      viable sperm cells compared to the other three solutions. When motile spermatozoa
      were incubated in solution C or solution D for 30 min, the result of HOST with
      solution C (10.8% dead spermatozoa) was superior to that of solution D (49.1%
      dead spermatozoa). In conclusion, the HOST protocol using 150 mOsm NaCl (solution
      C) for 1 min yielded the best results for selection of viable spermatozoa. This
      procedure should be used for selection of viable spermatozoa for ICSI in patients
      with 100% non-motile spermatozoa.

PMID- 9194678
TI  - Cervical pregnancy following ultrasound-guided embryo transfer. Methotrexate
      treatment in spite of high beta-HCG levels.

PMID- 9194679
TI  - Development of a successful ICSI programme without the use of PVP.

PMID- 9194680
TI  - Development of a successful ICSI programme without the use of PVP.

PMID- 9194681
TI  - Pharmacological actions of melatonin in oxygen radical pathophysiology.
AB  - Melatonin, the chief secretory product of the pineal gland, was recently found to
      be a free radical scavenger and antioxidant. This review briefly summarizes the
      published reports supporting this conclusion. Melatonin is believed to work via
      electron donation to directly detoxify free radicals such as the highly toxic
      hydroxyl radical. Additionally, in both in vitro and in vivo experiments,
      melatonin has been found to protect cells, tissues and organs against oxidative
      damage induced by a variety of free radical generating agents and processes,
      e.g., the carcinogen safrole, lipopolysaccharide, kainic acid, Fenton reagents,
      potassium cyanide, L-cysteine, excessive exercise, glutathione depletion, carbon
      tetrachloride, ischemia-reperfusion, MPTP, amyloid beta (25-35 amino acid
      residue) protein, and ionizing radiation. Melatonin as an antioxidant is
      effective in protecting nuclear DNA, membrane lipids and possibly cytosolic
      proteins from oxidative damage. Also, melatonin has been reported to alter the
      activities of enzymes which improve the total antioxidative defense capacity of
      the organism, i.e., superoxide dimutase, glutathione peroxidase, glutathione
      reductase, glucose-6-phosphate dehydrogenase, and nitric oxide synthase. Most
      studies have used pharmacological concentrations or doses of melatonin to protect
      against free radical damage; in a few studies physiological levels of the indole
      have been shown to be beneficial against oxidative stress. Melatonin's function
      as a free radical scavenger and antioxidant is likely assisted by the ease with
      which it crosses morphophysiological barriers, e.g., the blood-brain barrier, and
      enters cells and subcellular compartments. Whether the quantity of melatonin
      produced in vertebrate species is sufficient to significantly influence the total
      antioxidative defense capacity of the organism remains unknown, but its
      pharmacological benefits seem assured considering the low toxicity of the
      molecule.

PMID- 9194682
TI  - Blood transferrin and ferritin in Alzheimer's disease.
AB  - In the present study we found a significant correlation between severity of
      dementia of Alzheimer's type (DAT) and both transferrin and ferritin serum
      levels. Levels of transferrin in serum of 41 DAT patients tended to be lower than
      those of 19 age-matched controls, while levels of ferritin were not significantly
      different in DAT patients compared to controls. These results are interpreted in
      line with previous findings of higher brain ferritin and lower brain transferrin
      levels in DAT and are a circumstantial support for the oxygen radical hypothesis
      of degenerative brain disease.

PMID- 9194683
TI  - Inhibitory effect of albumin-derived advanced glycosylation products on PMA
      induced superoxide anion production by rat macrophages.
AB  - Advanced glycosylation end products (AGE) are implicated in many of the
      complications of diabetes. In the same way, infectious diseases are frequently
      associated with this disease. An impaired respiratory burst in macrophages may be
      a cause of infectious complications in diabetic patients. To establish a possible
      mechanism of this altered cell function, we have analyzed the effect of AGE
      modified proteins on PMA-dependent superoxide anion production (O2.-) from normal
      rat peritoneal macrophages. We have used AGE-modified bovine serum albumin (AGE
      BSA) prepared by incubation with glucose. AGE-BSA partially inhibits the phorbol
      ester-dependent superoxide production by macrophages in vitro. The specificity of
      this inhibitory effect is demonstrated by the fact that aminoguanidine, an
      inhibitor of the formation of AGE products, fully prevents the effect of AGE-BSA
      in vitro. Macrophages from diabetic rats shown an inhibition on PMA dependent-O2.
      production. However, the treatment in vivo with aminoguanidine produced a
      cancelation of the inhibitory effect observed in the diabetic state. These data
      suggest that AGE-modified proteins could be implicated in the impairment of
      macrophage respiratory burst in diabetes.

PMID- 9194684
TI  - Differential effects of low- and high-dose estrogen treatments on vascular
      responses in female rats.
AB  - In an attempt to study the mechanisms by which estrogens affect vascular
      responses, we utilized aortic preparations from intact and ovariectomized female
      rats receiving low- and high-dose subcutaneous estrogen treatments. Oil-treated,
      as well as male rats, served as controls. In ovariectomized females, low-dose 17
      beta-estradiol injections (5 microg/kg daily for two days) affected the basal
      release of nitric oxide, as evaluated by concentration-related curves to
      superoxide dismutase and N(G)-Methyl-L-arginine acetate, which was found to be
      greater in 17-beta-estradiol-treated females compared to oil-treated females or
      males. Conversely, the nitric oxide-related vascular relaxation evoked by
      acetylcholine and sodium nitroprusside was unchanged. Prostacyclin production was
      also evaluated. Aortic rings from ovariectomized 17-beta-estradiol-treated
      females released significantly more prostacyclin than those from oil-treated
      females. These results point out a possible role for nitric oxide and
      prostacyclin in the vascular protection brought about by physiological levels of
      estrogens. When intact females were treated with high doses of ethynilestradiol
      (100 microg/Kg daily for one month), a component of contraceptive pills, either
      the basal release of nitric oxide, or acetylcholine-induced relaxation underwent
      a significant decrease. Likewise, the relaxant responses to sodium nitroprusside
      were impaired in the aortic rings obtained from ethynilestradiol-treated animals
      when compared to controls. Similarly, the amount of prostacyclin released from
      aortic tissues obtained from ethynilestradiol-treated animals was significantly
      reduced. These results may provide a possible explanation for the higher
      incidence of cardiovascular disease in women who take contraceptive preparations
      containing high doses of estrogens.

PMID- 9194685
TI  - Effect of prior nicotine treatment on drug induced changes in serum LH
      concentrations in rats.
AB  - The effect of daily injections of nicotine on drug induced changes in LH
      secretion was investigated in male rats. Daily administration of nicotine for 7
      days resulted in decreased basal serum LH concentrations. Nicotine treatment
      blocked naloxone induced LH release and reduced LHRH induced increases in serum
      LH. Clonidine induced increases in serum LH were not altered by nicotine
      treatment and haloperidol treatment did not alter nicotine induced decreases in
      serum LH. In an acute study nicotine blocked LH secretion induced by the long
      acting opioid antagonist naltrexone. Collectively these results indicate that
      opioidergic neurons are involved in the reduction in serum LH that occurs
      following nicotine. They also indicate that chronic nicotine treatment can reduce
      the pituitary gland response to LHRH.

PMID- 9194686
TI  - Effects of aging on the activities of pyruvate dehydrogenase complex and its
      kinase in rat heart.
AB  - Effects of aging on the activities of heart pyruvate dehydrogenase complex and
      pyruvate dehydrogenase kinase were examined using 7, 35 and 60 wk old rats. Aging
      did not affect the total activity of pyruvate dehydrogenase complex but decreased
      the activity state (percentage of active form) of the complex in rats under the
      fed condition (52%, 36% and 26% for 7, 35 and 60 wk old rats, respectively). This
      decrease in the complex activity with aging was suggested to be associated with
      an age-related decrease in the blood glucose disposal. Starvation for 24 h
      decreased the activity state to less than 3% in all of the age groups. The
      activity of pyruvate dehydrogenase kinase associated with the complex was not
      related to the alteration in the activity state of the complex; the kinase
      activity was slightly lower in 60 wk old rats than in the younger rats under the
      fed condition and activation of the kinase by starvation was greater in the
      younger rats. The mechanism for the decrease in activity of pyruvate
      dehydrogenase complex was discussed on the basis of glucose and fatty acid
      utilization of heart muscle cells.

PMID- 9194687
TI  - Social deprivation stress induces adaptative changes of opioid mechanisms in the
      rat tail artery.
AB  - Brief (7-14 days) social deprivation stress has been found to increase blood
      pressure in Wistar rats, an effect dependent on activation of opioid function.
      The role of central opioids in this and other responses to stress has been
      repeatedly determined, but the possible involvement of modifications of
      peripheral opioid mechanisms is poorly understood. To further increase this
      knowledge, we have examined the opioid sensitivity of tail arteries taken from
      social deprived Wistar rats by studying the effect of beta-endorphin and DADLE
      "in vitro". Both opioids inhibited the electrically-induced constriction of the
      preparations in a dose-dependent manner, but these actions were significantly
      attenuated after 7-14 days of social deprivation. When the rats were isolated for
      30-35 days, the hypertensive response was still present but the arteries from
      group-housed and isolated animals no longer showed differential sensitivity to
      opioids. This difference with respect to 7-14 days of isolation could be related
      to age-dependent changes of opioid function, which were observed among group
      housed animals. The results suggest that social deprivation stress induces an
      adaptation of the tail arteries to the opioid effects on contractility. It is
      suggested that this endogenous adaptation could be contributing to the
      hypertensive response observed after social deprivation.

PMID- 9194688
TI  - Pharmacologic inhibition of transglutaminase-induced cross-linking of Alzheimer's
      amyloid beta-peptide.
AB  - The brain of Alzheimer's disease (AD) patients contains deposits of amyloid beta
      peptide (A beta). Recent studies have shown that A beta is a substrate for tissue
      transglutaminase (TGase), which induces the formation of cross-linked dimers and
      polymers, and that tacrine, indomethacin and deferoxamine, which have widely
      different chemical structures, attenuate the progression of symptoms of AD. This
      report evaluated the potential of a total of ten different pharmacological agents
      to inhibit TGase-induced cross-linking of A beta, including known TGase
      inhibitors (dansylcadaverine, spermine), non-steroidal anti-inflammatory drugs
      (indomethacin, meclofenamic acid, diflunisal, salicylic acid), monoamine oxidase
      inhibitors (tranylcypromine, phenelzine), an acetylcholinesterase inhibitor
      (tacrine), and an iron chelating agent (deferoxamine). All but one (salicylic
      acid) of these ten agents had an inhibitory effect on TGase-induced A beta cross
      linking. These results suggest that inhibition of TGase-induced cross-linking of
      A beta is a potential pharmacologic target for the treatment of AD. A method is
      also presented for the determination of percent inhibition of TGase-induced A
      beta cross-linking based on the separated monomer, dimer and polymer bands on SDS
      PAGE gels.

PMID- 9194689
TI  - Cyclic AMP and cyclic GMP relax phorbol ester-induced contractions of rat aorta
      by different mechanisms.
AB  - This study was designed to test the hypothesis that 8-Br-cAMP and 8-Br-cGMP
      dependent relaxation of phorbol dibutyrate stimulated contractions of intact rat
      aorta are independent of changes in the level of myosin light chain
      phosphorylation. Phorbol dibutyrate stimulated contraction with a concomitant
      increase in myosin light chain phosphorylation in normal tissues and without an
      increase in myosin light chain phosphorylation in calcium-depleted tissues.
      Phorbol dibutyrate stimulated contractions in normal CaCl2-containing
      physiological salt solution were relaxed in a concentration-dependent manner by 8
      Br-cAMP and 8-Br-cGMP. Phorbol dibutyrate-induced contractions in the absence of
      Ca2+ were only relaxed by 8-Br-cGMP; 8-Br-cAMP had no effect. The relaxation
      induced by 8-Br-cGMP was associated with a decrease in myosin light chain
      phosphorylation suggesting that cGMP-dependent protein kinase may alter the
      activity of either the myosin light chain kinase or phosphatase. The relaxation
      induced by 8-Br-cAMP was not associated with a decrease in phosphorylation
      suggesting that cAMP-dependent protein kinase may uncouple myosin light chain
      phosphorylation from force.

PMID- 9194690
TI  - Methylprednisolone inhibits neutrophil-endothelial cell interactions induced by
      interleukin-1beta under flow conditions.
AB  - The effects of methylprednisolone (m-PSL) on IL-1beta-induced neutrophil
      endothelial cell interactions, which are normally mediated by increased
      expression of both intercellular adhesion molecule-1 (ICAM-1) and E-selectin on
      endothelial cells, were examined using an in vitro flow system. Human
      neutrophilic polymorphonuclear leukocytes (PMN) were perfused at a shear stress
      of 1 dyne/cm2 on human umbilical vein endothelial cells (HUVEC) pretreated with
      IL-1beta (20 U/mL) for 4 hours. Many PMN adhered to IL-1-stimulated HUVEC and
      then migrated beneath endothelial cell monolayers. Treatment of HUVEC with m-PSL
      inhibited adherence and migration of PMN in a dose dependent manner. M-PSL also
      inhibited IL-1beta-induced upregulation of E-selectin and ICAM-1 on HUVEC in a
      dose dependent manner. These results suggest that m-PSL works as an anti
      inflammatory agent through inhibiting PMN-endothelial cell interactions.

PMID- 9194691
TI  - Effect of Cordyceps sinensis on the proliferation and differentiation of human
      leukemic U937 cells.
AB  - Cordyceps sinensis is a herb medicine with antitumor activity capable of
      suppressing the growth of mouse Sarcoma 180 in vivo. In the present study, we
      have isolated polysaccharide fraction of Cordyceps sinensis (PSCS) and
      investigated its effect on the proliferation and differentiation of human
      leukemic U937 cells using an in vitro culture system. Our results showed that the
      conditioned medium from PSCS (10 microg/ml)-stimulated blood mononuclear cells
      (PSCS-MNC-CM) had an activity that could significantly inhibit the proliferation
      of U937 cells resulting in a growth inhibition rate of 78-83%. Furthermore, PSCS
      MNC-CM treatment induced about 50% of the cells differentiating into mature
      monocytes/macrophages expressing nonspecific esterase (NSE) activity and the
      surface antigens of CD11b, CD14, and CD 68. Yet, the differentiated U937 cells
      also had functions of phagocytosis and superoxide production. However, PSCS alone
      or normal MNC-CM had no such effects. The levels of interferon (IFN)-gamma, tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-1 were very low in normal MNC
      CM, and they were greatly increased in MNC-CM prepared with PSCS stimulation.
      Antibody neutralization studies further revealed that the tumoricidal and
      differentiating effects of PSCS-MNC-CM were mainly derived from the elevated
      cytokines, especially IFN-gamma and TNF-alpha. These two cytokines acted
      synergistically on inhibiting cell growth and inducing differentiation of the
      target U937 cells.

PMID- 9194692
TI  - Divergent actions of chronic insulin treatment in vivo versus acute treatment ex
      vivo on diabetic-induced endothelial dysfunction.
AB  - Streptozotocin-induced diabetes is associated with hyperglycemia and
      hypoinsulinemia. The role of insulin in diabetes-induced endothelial dysfunction
      is unknown. In the present study, we evaluated the effect of chronic insulin
      treatment in vivo versus acute insulin administration ex vivo on endothelium
      dependent relaxation in aortic rings of the streptozotocin-induced diabetic rat.
      Relaxation to acetylcholine (but not A23187) was impaired in diabetic compared to
      control rings. This defect was prevented by chronic insulin treatment but was not
      reversed by acute insulin administration ex vivo. Thus, endothelial dysfunction
      in the streptozotocin-induced diabetic rat is specific for the chronic diabetic
      state and not to vascular toxicity of streptozotocin. Nevertheless, it is
      apparent that insulin at a physiological concentration does not cause an acute
      direct effect on facilitating endothelium-dependent relaxation in diabetic blood
      vessels.

PMID- 9194693
TI  - Contractile and relaxant effects of dimaprit on guinea pig isolated intestinal
      cells.
AB  - The effect of the histamine H2 receptor agonist dimaprit on intestinal
      contractility was characterized on smooth muscle cells isolated from the
      longitudinal muscle of the guinea pig ileum. Dimaprit exerted two opposite
      effects on the contractility of isolated muscle cells: relaxation of
      cholecystokinin octapeptide (CCK-8)-induced contractions in the range of
      concentrations 10(-17)-10(-13) M and contraction at concentrations higher than
      10(-13) M. The relaxant effect of dimaprit was totally prevented by the H2
      blocker famotidine (10(-7) M), which, at the same time, enhanced the contractile
      effect of dimaprit, shifting to the left the concentration-response curve to the
      agonist. This contraction was not modified by the histamine H1 receptor
      antagonists pyrilamine and temelastine, tested both at 10(-7) M. By contrast,
      atropine 10(-8) M abolished the contractile effect of dimaprit, while leaving
      unchanged the response to CCK-8. Our results clearly indicate that longitudinal
      muscle cells of the guinea pig ileum possess inhibitory H2 receptors, which can
      be activated by very low concentrations of dimaprit; moreover, they revealed that
      dimaprit can have non-histaminergic effects, probably due to muscarinic receptor
      activation; however, concentrations about 10000 times higher than those necessary
      to activate H2 receptors, are required.

PMID- 9194694
TI  - Polysaccharopeptide from Coriolus versicolor has potential for use against human
      immunodeficiency virus type 1 infection.
AB  - Polysaccharopeptide (PSP) isolated from the edible mushroom Coriolus versicolor
      was tested for its potential as an anti-human immunodeficiency virus type 1 (HIV
      1) compound in a series of in vitro assays. It demonstrated inhibition of the
      interaction between HIV-1 gp 120 and immobilized CD4 receptor (IC50 = 150
      microg/ml), potent inhibition of recombinant HIV-1 reverse transcriptase (IC50 =
      6.25 microg/ml), and inhibited a glycohydrolase enzyme associated with viral
      glycosylation. These properties, coupled with its high solubility in water, heat
      stability and low cytotoxicity, make it a useful compound for further studies on
      its possible use as an anti-viral agent in vivo.

PMID- 9194695
TI  - Mechanism of the inhibition of neuronal nitric oxide synthase by 1-(2
      trifluoromethylphenyl) imidazole (TRIM).
AB  - We have previously reported that 1-(2-trifluoromethylphenyl) imidazole (TRIM) is
      a potent inhibitor of mouse cerebellar neuronal NOS (nNOS) in vitro with very
      much reduced activity against bovine aortic endothelial NOS (eNOS). Using
      purified rat brain nNOS as enzyme source we have now probed the mechanism of
      action of TRIM. nNOS activity was linear over the first 5 min incubation. Optimal
      enzyme activity occurred in the presence of NADPH (0.5 mM), calcium chloride (75
      microM), tetrahydrobiopterin (12 microM) and calmodulin (10 microg/ml) as
      cofactors. TRIM was a poor inhibitor of nNOS (IC50, 462.0 microM) compared with L
      N(G) nitro arginine (L-NOARG, IC50, 0.32 microM). Removal of tetrahydrobiopterin
      (but not calmodulin) from the incubation medium greatly enhanced the nNOS
      inhibitory activity of TRIM (IC50, 32.0 microM) but not L-NOARG (IC50, 0.34
      microM). In the absence of added tetrahydrobiopterin, TRIM competed with L
      arginine for the substrate binding site on the nNOS enzyme with a Ki value of
      47.3 microM. The present experiments suggest that TRIM interferes with the
      binding of both L-arginine and tetrahydrobiopterin to their respective sites on
      the nNOS enzyme.

PMID- 9194696
TI  - A mutation in the Bordetella bronchiseptica bvgS gene results in reduced
      virulence and increased resistance to starvation, and identifies a new class of
      Bvg-regulated antigens.
AB  - The Bordetella BvgAS signal-transduction system has traditionally been viewed as
      mediating a transition between two distinct phenotypic phases: the Bvg+ phase,
      characterized by the expression of adhesins and toxins, and the Bvg-phase,
      characterized by motility in Bordetella bronchiseptica and by the expression of
      vrg loci in Bordetella pertussis. In B. bronchiseptica, the Bvg+ phase is
      necessary and sufficient for respiratory tract colonization whereas the Bvg phase
      is required for growth under nutrient-limiting conditions. This report describes
      the characterization of a mutant that is locked in a Bvg-intermediate (Bvg[i])
      phase. The mutation conferring this phenotype, designated bvgS-I1, results in a
      threonine-to-methionine substitution near the primary site of phosphorylation in
      BvgS. Compared to its Bvg+-phase-locked parent, the Bvg(i) mutant displays
      increased resistance to nutrient limitation and reduced virulence. Molecular
      analyses indicate that the mutant has lost the ability to express a subset of
      Bvg+-phase factors and has gained the ability to express factors unique to the
      Bvg(i) phase. Although identified by mutation, this work indicates that the
      Bvg(i) phase is expressed by wild-type B. bronchiseptica in response to certain
      (semi-modulating) environmental conditions. The identification of Bvg(i)-specific
      antigens suggests the existence of a new class of Bvg-regulated genes. We
      hypothesize that BvgAS is capable of mediating the expression of a spectrum of
      phenotypic phases in response to the various environments encountered as
      Bordetella travels within and between mammalian hosts.

PMID- 9194697
TI  - Structural analysis of the subunits of the trehalose-6-phosphate
      synthase/phosphatase complex in Saccharomyces cerevisiae and their function
      during heat shock.
AB  - Synthesis of trehalose in the yeast Saccharomyces cerevisiae is catalysed by the
      trehalose-6-phosphate (Tre6P) synthase/phosphatase complex, which is composed of
      at least three different subunits encoded by the genes TPS1, TPS2, and TSL1.
      Previous studies indicated that Tps1 and Tps2 carry the catalytic activities of
      trehalose synthesis, namely Tre6P synthase (Tps1) and Tre6P phosphatase (Tps2),
      while TsI1 was suggested to have regulatory functions. In this study two
      different approaches have been used to clarify the molecular composition of the
      trehalose synthase complex as well as the functional role of its potential
      subunits. Two-hybrid analyses of the in vivo interactions of Tps1, Tps2, TsI1,
      and Tps3, a protein with high homology to TsI1, revealed that both TsI1 and Tps3
      can interact with Tps1 and Tps2; the latter two proteins also interact with each
      other. In addition, trehalose metabolism upon heat shock was analysed in a set of
      16 isogenic yeast strains carrying deletions of TPS1, TPS2, TSL1, and TPS3 in all
      possible combinations. These results not only confirm the previously suggested
      roles for Tps1 and Tps2, but also provide, for the first time, evidence that TsI1
      and Tps3 may share a common function with respect to regulation and/or structural
      stabilization of the Tre6P synthase/phosphatase complex in exponentially growing,
      heat-shocked cells.

PMID- 9194698
TI  - Non-invasive Salmonella typhimurium mutants are avirulent because of an inability
      to enter and destroy M cells of ileal Peyer's patches.
AB  - Salmonella typhimurium initiates infection of a host by invading M cells of
      Peyer's patches within the small intestine. The ability of the bacteria to invade
      mammalian cells has been shown to be regulated by environmental conditions,
      including oxygen concentrations, osmolarity, and growth phase. We have previously
      created oxygen-regulated Tn5lacZY S. typhimurium mutants that are defective in
      invasion. We have now identified the invasion genes disrupted by eight of the
      transposon insertions. These genes encode transcriptional regulators (hilA and
      invF), type III secretory components (orgA, invG and spaR) and secreted proteins
      (invC and invD). Examination of the protein-secretion profiles of the non
      invasive mutants indicated that each of the mutants was defective in secretion of
      between one and six proteins. We have also demonstrated that the loss of tissue
      culture cell invasiveness corresponds to an inability to invade and destroy M
      cells of Peyer's patches in a murine ligated loop model. Virulence studies,
      performed in mice, demonstrated that these defects significantly reduced the
      ability of the mutants to cause murine typhoid fever by an oral route of
      infection. Virulence by an intraperitoneal route of infection was unaffected. The
      data indicate that in vitro invasiveness, invasion-protein secretion, and M-cell
      invasion are critical indicators of S. typhimurium virulence.

PMID- 9194699
TI  - Normal processing of AP sites in Apn1-deficient Saccharomyces cerevisiae is
      restored by Escherichia coli genes expressing either exonuclease III or
      endonuclease III.
AB  - Escherichia coli exonuclease III and endonuclease III are two distinct DNA-repair
      enzymes that can cleave apurinic/apyrimidinic (AP) sites by different mechanisms.
      While the AP endonuclease activity of exonuclease III generates a 3'-hydroxyl
      group at AP sites, the AP lyase activity of endonuclease III produces a 3'
      alpha,beta unsaturated aldehyde that prevents DNA-repair synthesis. Saccharomyces
      cerevisiae Apn1 is the major AP endonuclease/3'-diesterase that also produces a
      3'-hydroxyl group at the AP site, but it is unrelated to either exonuclease III
      or endonuclease III. apn1 deletion mutants are unable to repair AP sites
      generated by the alkylating agent methyl methane sulphonate and display a
      spontaneous mutator phenotype. This work shows that either exonuclease III or
      endonuclease III can functionally replace yeast Apn1 in the repair of AP sites.
      Two conclusions can be derived from these findings. The first of these
      conclusions is that yeast cells can complete the repair of AP sites even though
      they are cleaved by AP lyase. This implies that AP lyase can contribute
      significantly to the repair of AP sites and that yeast cells have the ability to
      process the alpha,beta unsaturated aldehyde produced by endonuclease III. The
      second of these conclusions is that unrepaired AP sites are strictly the cause of
      the high spontaneous mutation rate in the apn1 deletion mutant.

PMID- 9194700
TI  - Inactivation of the replication-termination system affects the replication mode
      and causes unstable maintenance of plasmid R1.
AB  - Two so-called Ter sites, which bind the Escherichia coli Tus protein, are located
      near the replication origin of plasmid R1. Inactivation of the tus gene caused a
      large decrease in the stability of maintenance of the R1 mini-derivative pOU47
      despite the presence of a functional partition system on the plasmid. Deletion of
      the right Ter site caused a drop in stability similar to that observed after
      inactivation of the tus gene. Substitution of 2bp required for Tus binding also
      caused unstable plasmid maintenance, whereas no effects on stability were
      observed when the left Ter site was deleted. Inactivation of the tus gene was
      coupled to an increased occurrence of multimeric plasmid forms as shown by gel
      electrophoresis of pOU47 DNA. Inactivation of the recA gene did not increase
      plasmid stability, suggesting that the multimerization was not mediated by RecA.
      Plasmid DNA was isolated from the tus strain carrying plasmid pOU47 and from a
      wild-type strain carrying pOU47 in which the right Ter site had been inactivated;
      in both cases, electron microscopy revealed the presence of multimers as well as
      rolling-circle structures with double-stranded tails. Thus, the right Ter site in
      plasmid R1 appears to stabilize the plasmid by preventing multimerization and
      shifts from theta to rolling-circle replication.

PMID- 9194701
TI  - In vivo mobility of a group I twintron in nuclear ribosomal DNA of the myxomycete
      Didymium iridis.
AB  - DiSSU1 is an optional group I twintron present in the nuclear extrachromosomal
      ribosomal DNA of the myxomycete Didymium iridis. DiSSU1 appears to be complex
      both in structure and function. At the RNA level it has a twin-ribozyme
      organization composed of two group I ribozymes with different functions,
      separated by an open reading frame. Here, we show that DiSSU1 is mobile when
      haploid intron-containing and intron-less amoebae are mated. The mobility process
      is fast, being completed in 5-10 nuclear cycles after mating in the developing
      zygote and plasmodia. Analyses of progeny from genetic crosses confirm intron
      mobility. DiSSU1 is the first example of a mobile group I twintron. The intron
      encoded protein was expressed in Escherichia coli and found to be an
      endonuclease, I-DirI, that cleaves an intron-less ribosomal DNA allele at the
      intron-insertion site, and is probably involved in intron homing. The
      endonuclease I-DirI seems to be a rare example of a protein that is expressed
      from a ribozyme-processed RNA polymerase I transcript in vivo.

PMID- 9194702
TI  - The invasion-associated type III system of Salmonella typhimurium directs the
      translocation of Sip proteins into the host cell.
AB  - The ability of Salmonella typhimurium to interact with host cells is largely
      dependent on the function of a type III protein-secretion system encoded at
      centisome 63 of its chromosome. We have shown here that two targets of this
      protein-secretion system, SipB and SipC, are translocated into cultured
      intestinal Henle-407 cells. Translocation required the function of the type III
      secretion apparatus, as an S. typhimurium strain carrying a mutation in invA,
      which encodes an essential component of this system, failed to translocate the
      Sip proteins. Null mutations in the genes encoding SipB, SipC or SipD, prevented
      protein translocation, indicating that these proteins are involved in the
      translocation process. In contrast, mutations in sipA and sptP, which also encode
      secreted proteins, did not interfere with the translocation of SipC, indicating
      that only a subset of targets of the type III secretion system act as
      translocases. Externally or internally localized bacteria could direct protein
      translocation into Henle-407 cells as this process occurred in the presence of
      cytochalasin D at a concentration that prevented bacterial entry, or in the
      presence of gentamicin added shortly after bacterial internalization at a
      concentration that killed extracellular Salmonella. These results indicate that
      protein translocation into host cells may be a universal function of all type III
      secretion systems.

PMID- 9194703
TI  - Two independent type III secretion mechanisms for YopE in Yersinia
      enterocolitica.
AB  - Pathogenic Yersinia species escape the infected host's defense mechanisms by
      targeting cytotoxic Yop proteins into the cytoplasm of macrophages via a type III
      secretion pathway. Two separate secretion signals contained in YopE were
      identified, each of which were sufficient but not necessary for the secretion of
      reporter molecules. One signal is located within the coding sequence of the first
      15 amino acids and is sufficient for the secretion of fusion proteins but not
      required for YopE secretion. The second signal is located downstream at residues
      15-100 of YopE and is only recognized by the type III machinery when it is bound
      to SycE. We propose the existence of two independent mechanisms that allow for
      the secretion of Yop proteins.

PMID- 9194704
TI  - EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia
      coli O157:H7 cleaves human coagulation factor V.
AB  - In this study, we identified and characterized a novel secreted protein, the
      extracellular serine protease EspP, which is encoded by the large plasmid of
      enterohaemorrhagic Escherichia coli (EHEC) O157:H7. The corresponding espP gene
      consists of a 3900 bp open reading frame that is able to encode a 1300-amino-acid
      protein. EspP is synthesized as a large precursor which is then processed at the
      N- and C-termini during secretion. It can be grouped into the autotransporter
      protein family. The deduced amino acid sequence of EspP showed homology to
      several secreted or surface-exposed proteins of pathogenic bacteria, in
      particular EspC of enteropathogenic E. coli and IgA1 proteases from Neisseria
      spp. and Haemophilus influenzae. Hybridization experiments and immunoblot
      analysis of clinical EHEC isolates showed that EspP is widespread among EHEC of
      the serogroup O157 and that it also exists in serogroup 026. A specific immune
      response against EspP was detected in sera from patients suffering from EHEC
      infections. Functional analysis showed that EspP is a protease capable of
      cleaving pepsin A and human coagulation factor V. Degradation of factor V could
      contribute to the mucosal haemorrhage observed in patients with haemorrhagic
      colitis.

PMID- 9194706
TI  - Involvement of the ribulosephosphate epimerase gene in the dnaA and dnaR
      functions for initiation of chromosome replication in Escherichia coli.
AB  - Initiation of replication of the Escherichia coli chromosome is rendered
      temperature-sensitive by the dnaR130 mutation in the prs gene that encodes
      phosphoribosylpyrophosphate synthetase. The thermosensitivity of the dnaR mutant
      is suppressed by a spontaneous mutation in rpe, the gene encoding
      ribulosephosphate epimerase. Disruption of the rpe gene reverses the
      thermosensitive growth of the dnaR mutant. The rpe-disrupted dnaR mutant exhibits
      extensive DNA synthesis at low and high temperatures, as does the dnaR+ rpe
      disruptant and the dnaR+ rpe+ strain. The thermoresistant DNA synthesis in the
      rpe dnaR double mutant is dnaA dependent, because the dnaA167 mutation renders
      the synthesis thermosensitive. The rpe-knockout mutation abolishes the ability of
      the dnaA115 allele to complement the defect of the dnaA167 mutant with or without
      the dnaR mutation and diminishes the dnaR-complementing ability of the dnaR224
      allele. These results show that the rpe product is involved in the functions of
      the products of both dnaA and dnaR for initiation of replication of the bacterial
      chromosome.

PMID- 9194705
TI  - Effect of mutations in Shigella flexneri chromosomal and plasmid-encoded
      lipopolysaccharide genes on invasion and serum resistance.
AB  - This study shows that both length and distribution of lipopolysaccharide (LPS)
      are important for Shigella flexneri invasion and virulence. Mutants were
      generated in the chromosomal LPS synthesis genes rfa, rfb, and rol, and in a
      plasmid-encoded O-antigen chain-length regulator, cld(pHS-2). LPS analysis showed
      that mutations in rfb genes and in a candidate rfaL gene either eliminated the
      entire O-antigen side chains or produced chains of greatly reduced length.
      Mutation in a previously unidentified gene, rfaX, affected the LPS core region
      and resulted in reduced amounts of O-antigen. Mutants defective in cld(pHS-2) or
      rol had different distributions of O-antigen chain lengths. The results of tissue
      culture cell invasion and plaque assays, the Sereny test, and serum-sensitivity
      assay suggested roles for the different LPS synthesis genes in bacterial survival
      and virulence; rfaL, rfaX and rfb loci are required for serum resistance and
      intercellular spread, but not for invasion; cld(pHS-2) is required for resistance
      to serum killing and for full inflammation in the Sereny test, but not for
      invasion or intercellular spread, while rol is required for normal invasiveness
      and plaque formation, but not for serum resistance. Thus, O-antigen synthesis and
      chain-length regulation genes encoded on both the chromosome and the small
      plasmid pHS-2 play important roles in S. flexneri invasion and virulence.

PMID- 9194707
TI  - Mutual control of the PecS/PecM couple, two proteins regulating virulence-factor
      synthesis in Erwinia chrysanthemi.
AB  - The Erwinia chrysanthemi pecS mutant displays constitutive production of
      virulence factors, such as pectinases or cellulases. Complementation of the pecS
      mutation can be obtained in the presence of the pecS wild-type gene on a low-copy
      number plasmid. Moreover, the resulting plasmid decreases the expression of a
      pecS::uidA chromosomal fusion, indicating the existence of an autoregulation
      mechanism. This negative autoregulation was confirmed and quantified by analysis
      of the pecS transcripts using primer-extension experiments. Band-shift assays and
      DNase I footprinting experiments demonstrated that the PecS protein could bind to
      the intergenic regulatory region, located between the pecS and pecM genes, with a
      relatively high affinity (apparent dissociation constant (K'[d]) close to 4nM).
      These PecS-binding sites overlap the pecS and pecM promoters. The comparison of
      these new PecS-binding sites with those previously characterized on the target
      genes confirms the absence of a consensus. This observation was in accordance
      with the results of the missing-contact experiments performed on the pecS-pecM
      intergenic regulatory region and the celZ operator. Concurrently, we demonstrated
      that the PecS protein negatively controls the expression of the divergently
      transcribed pecM gene located 400bp upstream from the pecS gene. By following the
      efficiency of pecS autoregulation in a double E. chrysanthemi pecM-pecS mutant,
      we established that the PecM protein potentiates PecS activity in vivo.

PMID- 9194708
TI  - Characterization of BpH3, an H-NS-like protein in Bordetella pertussis.
AB  - This study describes the characterization of BpH3, a Bordetella pertussis DNA
      binding protein. Sequence analysis reveals significant homology with the H-NS
      sequence of Escherichia coli and Haemophilus influenzae, particularly in the C
      terminal part of the proteins. Our results provide evidence that H-NS and BpH3
      display functional homology. First, expression of BpH3 in an hns mutant results
      in restoration of motility, an H-NS-dependent phenotype. This effect is dependent
      on the level of BpH3 expression and results from transcriptional activation of
      the flagellar master operon. Second, the high level of beta-glucosidase
      associated with hns mutations is reversed to the low wild-type level in the
      presence of BpH3. Third, BpH3 is able, like H-NS, to preferentially bind in vitro
      to curved DNA fragments, such as flhDC and bla promoter regions. Our results are
      the first demonstration that proteins homologous to H-NS exist in bacteria
      phylogenetically distant from H. influenzae and enterobacteria.

PMID- 9194709
TI  - Role of the transcriptional activator RocR in the arginine-degradation pathway of
      Bacillus subtilis.
AB  - In Bacillus subtilis, genes involved in arginine and ornithine catabolism
      constitute two operons, rocABC and rocDEF. Inducible expression of these two
      operons is SigL-dependent and requires the transcriptional activator RocR. RocR
      is a member of the NtrC/NifA family of regulators. To study the molecular
      mechanisms leading to the activation of RocR, we constructed a series of mutants
      affected in various steps of arginine catabolism. Results obtained using these
      mutants strongly suggest that the true inducer is ornithine or citrulline.
      Constitutive mutants of rocR containing either missense mutations, frameshift
      mutations resulting from deletions, or in-frame deletions leading to the
      synthesis of N-terminal truncated RocR polypeptides were obtained. Analysis of
      these mutants indicates that the N-terminal part of RocR is an intramolecular
      repressor domain. AhrC is a second positive regulatory protein of the rocABC and
      rocDEF operons. Two missense mutations modifying the N-terminal domain of RocR
      led to high constitutive expression of the Roc regulon in the absence of AhrC.
      Constitutive RocR proteins still require the presence of UAS1 and therefore
      probably bending of the DNA region located between the UAS1 and the promoter,
      suggesting that AhrC is not involved in DNA bending which facilitates interaction
      between RocR and sigma54-RNA polymerase. We suggest that the positive role of
      AhrC involves protein-protein interaction with RocR.

PMID- 9194710
TI  - Starvation-independent sporulation in Myxococcus xanthus involves the pathway for
      beta-lactamase induction and provides a mechanism for competitive cell survival.
AB  - Myxococcus xanthus is a Gram-negative, soil-dwelling bacterium with a complex
      life cycle which includes fruiting body formation and sporulation in response to
      starvation. This developmental process is slow, requiring a minimum of 24-48 h,
      and requires cells to be at high cell density on a solid surface. It is known
      that, in the absence of starvation, vegetatively growing cell suspensions can
      form 'glycerol spores' when exposed to high levels of glycerol, usually 0.5 M.
      The cells differentiate from rods to resistant spheres rapidly (2-4 h) and
      synchronously. We have found that the chromosomally encoded beta-lactamase of M.
      xanthus can be induced by numerous beta-lactam antibiotics as well as by non
      specific inducers including glycine and many D-amino acids. In addition, D
      cycloserine, phosphomycin, and hen egg-white lysozyme also induce beta-lactamase
      in this bacterium. Unexpectedly, agents which induce beta-lactamase can induce
      'glycerol spores'; all of the agents tested which induce glycerol spores
      (glycerol, DMSO, ethylene glycol) also induce beta-lactamase. During the
      induction of sporulation, beta-lactamase activity increases, reaching a peak
      during the morphological transition from rod-shaped cells to spherical spores.
      These spores are viable and resistant to many treatments which disrupt
      vegetatively growing rods but are not as resistant as fruiting body spores. The
      concomitant induction of beta-lactamase and starvation-independent sporulation
      suggests that these processes share a common signal-transduction pathway. These
      results also suggest that starvation-independent sporulation may be an adaptation
      of cells in order to resist agents that damage peptidoglycan structure and
      therefore threaten cell survival.

PMID- 9194711
TI  - Iron-regulated haemolysin gene from Edwardsiella tarda.
AB  - We have cloned and sequenced the haemolysin gene locus from Edwardsiella tarda
      (ETH). This region encoded two open reading frames, designated ethA and ethB.
      ethA is the haemolysin gene consisting of 4782bp encoding a product of 165.3 kDa
      and ethB is an activation/secretion protein gene of 1677bp that encodes a product
      of 61.9 kDa. There were two putative ferric uptake regulator (Fur) binding sites
      on the 5' upstream region of the ethB gene overlapping the promoter region and
      ribosome-binding site. The haemolysin produced by the cloned gene was secreted by
      Escherichia coli. The deduced amino acid sequences of the ethA and ethB genes
      were found to be homologous to those of the haemolysin and activation/secretion
      proteins of Haemophilus ducreyi, Proteus mirabilis, and Serratia marcescens. E.
      coli carrying the ethA gene but not the ethB gene completely lost haemolytic
      activity, although the ethA gene was transcribed. The protein expressed by E.
      coli carrying a recombinant plasmid which encoded the ethA gene had
      haemagglutination activity. The EthB protein was necessary for activation of EthA
      protein (haemolysin). The ethA and ethB genes were very prevalent in haemolytic
      E. tarda strains isolated from diseased fish. Transcription of the ethB gene was
      regulated by iron. The ethA and ethB genes were transcribed independently.

PMID- 9194712
TI  - Catabolite repression by glucose 6-phosphate, gluconate and lactose in
      Escherichia coli.
AB  - While catabolite repression by glucose has been studied extensively and is
      understood in large detail in Enterobacteriaceae, catabolite repression by
      carbohydrates that are not transported by the phosphotransferase system (PTS) has
      always remained an enigma. Examples of non-PTS carbohydrates that cause
      catabolite repression in Escherichia coli are gluconate, lactose and glucose 6
      phosphate. In this article it is shown that enzyme IIA(Glc) of the PTS is not
      involved in catabolite repression by these carbon sources. Carbon sources that
      caused strong catabolite repression of beta-galactosidase lowered the
      concentration of both cAMP and the cAMP receptor protein (CRP). A strong
      correlation was found between the amounts of cAMP and CRP and the strength of the
      repression. The levels of cAMP and CRP were modulated in various ways. Neither
      overproduction of CRP nor an increased cAMP concentration could completely
      relieve the repression by glucose 6-phosphate, lactose and gluconate.
      Simultaneously increasing the cAMP and the CRP levels was lethal for the cells.
      In a mutant expressing a constant amount of cAMP-independent CRP* protein,
      catabolite repression was absent. The same was found in a mutant in which lac
      transcription is independent of cAMP/CRP. These results, combined with the fact
      that both the cAMP and the CRP levels are lowered by glucose 6-phosphate, lactose
      and gluconate, lead to the conclusion that the decreased cAMP and CRP levels are
      the cause of catabolite repression by these non-PTS carbon sources.

PMID- 9194713
TI  - Methanol production during chemotaxis to amino acids in Bacillus subtilis.
AB  - The 20 common amino acids act as attractants during chemotaxis by the Gram
      positive organism Bacillus subtilis. In this study, we report that all amino
      acids induce B. subtilis to produce methanol both upon addition and removal of
      the chemoeffector. Asparagine-induced methanol production is specific to the McpB
      receptor and aspartate-induced methanol production correlates with receptor
      occupancy. These findings suggest that addition and removal of all amino acids
      cause demethylation of specific receptors which results in methanol production.
      We also demonstrate that certain attractants cause greater production of methanol
      after multiple stimulations. CheC and CheD, while affecting the levels of
      receptor methylation, are not absolutely required for either methylation or
      demethylation. In contrast, CheY is necessary for methanol formation upon removal
      of attractant but not upon addition of attractant. We conclude that methanol
      formation due to negative stimuli indicates the existence of a unique
      adaptational mechanism in B. subtilis involving the response regulator, CheY.

PMID- 9194714
TI  - Do bacteria sing? Sonic intercellular communication between bacteria may reflect
      electromagnetic intracellular communication involving coherent collective
      vibrational modes that could integrate enzyme activities and gene expression.

PMID- 9194715
TI  - A new family of prokaryotic transport proteins: binding protein-dependent
      secondary transporters.

PMID- 9194716
TI  - Royal Australasian College of Surgeon annual scientific congress. Brisbane, 11-15
      May 1997. Abstracts.

PMID- 9194717
TI  - 49th American Association for Clinical Chemistry annual meeting. Atlanta,
      Georgia, July 20-24, 1997. Abstracts.

PMID- 9194718
TI  - 22nd International Epilepsy Congress. Dublin, Ireland, June 29-July 4, 1997.
      Abstracts.

PMID- 9194719
TI  - A controlled trial of oral acyclovir for the prevention of stromal keratitis or
      iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial
      Keratitis Trial. The Herpetic Eye Disease Study Group.
AB  - OBJECTIVE: To evaluate the efficacy of oral acyclovir in preventing stromal
      keratitis or iritis in patients with epithelial keratitis caused by herpes
      simplex virus (HSV). METHODS: Patients with HSV epithelial keratitis of 1-week or
      less duration were treated with topical trifluridine and were randomly assigned
      to receive a 3-week course of oral acyclovir, 400 mg 5 times a day (hereafter
      referred to as the acyclovir group), or placebo (hereafter referred to as the
      placebo group). The development of HSV stromal keratitis or iritis was assessed
      during 12 months of follow-up. RESULTS: Stromal keratitis or iritis developed in
      17 (11%) of the 153 patients in the acyclovir group and in 14 (10%) of the 134
      patients in the placebo group. Compared with the placebo group, the adjusted rate
      ratio for the development of stromal keratitis or iritis in the acyclovir group
      was 1.16 (95% confidence interval, 0.56-2.43). The development of stromal
      keratitis or iritis was more frequent in patients with a history of HSV stromal
      keratitis or iritis than in those without such a history (23% vs 9%; P = .01).
      CONCLUSIONS: For patients with HSV epithelial keratitis treated with topical
      trifluridine, no apparent benefit of a 3-week course of oral acyclovir in
      preventing HSV stromal keratitis or iritis was seen during the subsequent year.
      The 1-year rate of development of stromal keratitis or iritis was lower than
      previously reported in the literature, except in patients with a history of HSV
      stromal keratitis or iritis.

PMID- 9194720
TI  - Coexistent Acanthamoeba keratitis and herpetic keratitis.
AB  - OBJECTIVE: To describe a series of patients with proved herpes simplex virus
      keratitis (herpetic keratitis) who also had documented Acanthamoeba keratitis.
      METHODS: Herpetic keratitis was documented with viral cultures, immunologic
      stains, or histopathologic examination for multinucleated giant cells in the
      corneal epithelium. Acanthamoeba organisms were identified using confocal
      microscopy and epithelial biopsy with hematoxylin-eosin staining. Biopsy of the
      stroma and epithelium was used to identify Acanthamoeba organisms in 1 case.
      RESULTS: Cultures for herpes simplex virus were positive in 6 of the 9 cases.
      Immunologic stains were positive in an additional 2 cases, and in 1 case
      multinucleated giant cells were present in the epithelium consistent with the
      diagnosis of herpes simplex virus keratitis. Tandem scanning confocal microscopic
      findings were positive for Acanthamoeba in 8 of the 9 cases, and all of them
      demonstrated Acanthamoeba organisms in epithelial scrape biopsy specimens. In 1
      case, which was not evaluated with confocal microscopy, Acanthamoeba was detected
      using a stromal and epithelial biopsy. Two of the 9 patients had a history of
      contact lens use. CONCLUSION: Acanthamoeba keratitis may be present as a
      secondary or opportunistic infection in patients with herpetic keratitis.

PMID- 9194721
TI  - The value of routine donor corneal rim cultures in penetrating keratoplasty.
AB  - OBJECTIVE: To investigate the value of donor corneal rim cultures performed
      routinely at the time of penetrating keratoplasty. DESIGN: Retrospective review
      of Mayo Clinic medical records for all corneal transplantations for which donor
      rim cultures have been performed. MAIN OUTCOME MEASURES: Frequency of positive
      cultures, occurrence of endophthalmitis within 2 months of undergoing surgery,
      action taken in response to the culture results, and costs of cultures. RESULTS:
      Donor rim culture results were available for 1078 of 1083 consecutive
      transplantations performed from 1981 to 1995. Three cases of endophthalmitis
      (0.28%) and 1 suture abscess occurred. Rim cultures were negative in all of these
      cases. Action was documented in response to positive cultures in 17 cases (8.1%).
      The estimated average cost of routine rim cultures in 1994 was $137 per donor
      cornea. Bacterial or fungal cultures were positive in 209 (19.4%) cases. Two
      microorganisms were cultured simultaneously in 17 cases (1.6%) and 3 in 2 cases
      (0.2%). Staphylococcus coagulase-negative (130 cases [12.1%]), and Streptococcus
      species, viridans group (23 cases [2.1%]), were the most common isolates. Fifty
      two (62.7%) of 83 coagulase-negative Staphylococcus species isolates tested were
      resistant to gentamicin. There were more positive cultures from corneas stored in
      Optisol (37/183 [20%]) than in Optisol GS (16/144 [11%]) (P = .03). Fewer
      cultures were positive from live donors (9/93 [10%]) compared with cadaveric
      donors (181/ 909 [20%]) (P = .02). Positive cultures were more frequent for
      corneas excised in situ (39/125 [31.2%]) than for those enucleated (152/851
      [17.9%]) (P < .001). CONCLUSIONS: Despite differences in rates of positive donor
      rim cultures with different harvesting and storage techniques, for our practice,
      routine donor corneal rim cultures had no predictive value for infective
      complications of penetrating keratoplasty and, therefore, added an unnecessary
      expense to the management of our patients.

PMID- 9194722
TI  - Automatic detection of glaucomatous visual field progression with neural
      networks.
AB  - OBJECTIVE: To evaluate computerized neural networks to determine visual field
      progression in patients with glaucoma. METHODS: Two hundred thirty-three series
      of Octopus G1 visual fields of 181 patients with glaucoma were collected. Each
      series was composed of 4 or more reliable visual fields from patients who had
      previously undergone automated perimetry. The visual fields were independently
      evaluated in a masked fashion by 3 experienced observers (K.N.-M, M.W., and J.C.)
      and were judged to show progression based on the agreement of 2 observers. The
      stable and progressed series were matched for mean defect at baseline. The
      threshold data were submitted to a back propagation neural network that was
      trained to classify each series as stable or progressed. Two thirds of the data
      were used for the training and the remaining one third to test the performance of
      the network. This was repeated 3 times to classify all of the series (changing
      the training and test series). RESULTS: Fifty-nine series of visual fields showed
      progression and 151 were judged stable. Neural network sensitivity was 73% and
      specificity was 88% (threshold for progression = 0.5). The concordance of the
      neural network with the observers was good (0.50 < or = kappa > or = 0.64).
      CONCLUSIONS: A neural network can be trained to recognize visual field
      progression in good concordance with experienced observers. Neural networks may
      be used to aid the physician in the evaluation of glaucomatous visual field
      progression.

PMID- 9194723
TI  - Association of visual field, cup-disc ratio, and magnetic resonance imaging of
      optic chiasm.
AB  - OBJECTIVE: To assess the association of visual field, vertical cup-disc (VC/D)
      ratio, and vertical height of optic chiasm. DESIGN: Case series. SETTING:
      Outpatient eye clinic. PATIENTS: Eighteen patients with low, normal, or elevated
      intraocular pressure, with or without visual field defects. INTERVENTION:
      Measurement of visual field, VC/D ratio, and vertical height of optic chiasm.
      MAIN OUTCOME MEASURES: Association between VC/D ratio and visual field defects
      compared with association between vertical height of optic chiasm and visual
      field defects. RESULTS: Visual field defects were graded as 0, 1 to 10, and 11 to
      20 (from least to most severe). Group mean VC/D ratios were 0.47 (0), 0.55 (1
      10), and 0.69 (11-20) for right eyes and 0.48 (0), 0.57 (1-10), and 0.75 (11-20)
      for left eyes. The significance level for trend was P = .02 for right eyes and P
      = .006 for left eyes. Group mean chiasm heights were 3.5 (0), 2.9 (1-10), and 2.2
      (11-20) mm for right eyes and 3.5 (0), 2.8 (1-10), and 2.2 (11-20) mm for left
      eyes. The significance level for trend was P < .001 for right eyes and P = .002
      for left eyes. To assess the simultaneous effects of VC/D ratio and chiasm height
      on the visual field defects groups, we used ordinal logistic regression models.
      Models with both variables implied that chiasm height was a stronger predictor of
      visual field defects group than VC/D ratio (for right eyes, P = .04 [VC/D ratio],
      P = .001 [chiasm height]; for left eyes, P = .11 [VC/D ratio], P = .005 [chiasm
      height]). CONCLUSIONS: When chiasm and VC/D ratio were analyzed in the same
      model, chiasm height was a stronger predictor of visual field defects. In
      advanced visual field defects, the optic chiasm is atrophic.

PMID- 9194724
TI  - Iritis and hypotony after treatment with intravenous cidofovir for
      cytomegalovirus retinitis.
AB  - OBJECTIVE: To describe intraocular inflammation due to treatment with intravenous
      cidofovir dihydrate for cytomegalovirus retinitis. DESIGN: Retrospective cohort.
      SETTING: Three university outpatient ophthalmology clinics. PATIENTS: All
      patients treated with intravenous cidofovir therapy before October 31, 1996.
      INTERVENTION: Treatment with intravenous cidofovir was given according to
      standardized protocols. Intraocular inflammation was treated according to the
      best medical judgment. MAIN OUTCOME MEASURES: The presence of new intraocular
      inflammation, the severity of inflammation, visual acuity, and intraocular
      pressure. RESULTS: Eleven cases of iritis (26%) occurred among 43 patients. In 6
      cases, the iritis was bilateral. Patients who experienced iritis were more likely
      to have been previously treated for cytomegalovirus retinitis (P = .03), to be
      diabetic (P = .05), or to be receiving protease inhibitors (P < .001). Four
      patients and 15 control subjects had also taken rifabutin (P = .70). The onset of
      iritis occurred at a mean (+/-SD) of 4.9 +/- 1.8 days after a cidofovir dose and
      after a mean (+/-SD) of 4.2 +/- 1.6 doses of cidofovir. Six eyes of 4 patients
      had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity
      of at least 2 Snellen lines. CONCLUSIONS: Acute intraocular inflammation may
      occur with or without hypotony after intravenous cidofovir therapy, similar to
      the reactions seen after intravitreous administration. Although the
      manifestations may be severe, they are manageable with topical corticosteroid
      therapy in most cases. Cidofovir therapy can be continued in some patients if
      medical necessity warrants, but recurrent inflammation or permanent hypotony may
      occur.

PMID- 9194725
TI  - Risk factors for choroidal neovascularization in the second eye of patients with
      juxtafoveal or subfoveal choroidal neovascularization secondary to age-related
      macular degeneration. Macular Photocoagulation Study Group.
AB  - OBJECTIVES: To verify and quantify previously reported risk factors for
      development of choroidal neovascularization (CNV) in the fellow eye of patients
      with 1 eye affected with CNV secondary to age-related macular degeneration, to
      examine the value of characteristics of the pericentral macula in the
      quantification of risk for developing CNV, and to explore whether the presence of
      occult CNV in the first eye affects the development of CNV in the fellow eye.
      DESIGN, PATIENTS, AND SETTING: Follow-up study of fellow eyes of 670 patients
      enrolled in multicenter, randomized clinical trials of laser photocoagulation of
      juxtafoveal or subfoveal CNV. MAIN OUTCOME MEASURE: Development of CNV. RESULTS:
      Three characteristics of the central macula of the fellow eye and 1 systemic
      factor were associated independently with an increased risk of developing CNV:
      the presence of 5 or more drusen (relative risk, 2.1; 95% confidence interval,
      1.3-3.5), focal hyperpigmentation (relative risk, 2.0; 95% confidence interval,
      1.4-2.9), 1 or more large drusen (relative risk, 1.5; 95% confidence interval 1.0
      2.2), and definite systemic hypertension (relative risk, 1.7; 95% confidence
      interval, 1.2-2.4). Estimated 5-year incidence rates ranged from 7% for the
      subgroup with no risk factors to 87% for the subgroup with all 4 risk factors.
      Characteristics of the pericentral macula were not strongly associated with the
      development of CNV. The presence of occult CNV in the first eye affected had no
      influence on the development of CNV or on the type of CNV in the fellow eye.
      CONCLUSIONS: The prognosis of the fellow eye is affected strongly by
      characteristics of its central macula and by systemic hypertension. These factors
      should be considered when counseling patients with unilateral neovascular age
      related macular degeneration and when targeting patients for preventive
      interventions.

PMID- 9194726
TI  - Head turn in 1-eyed and normally sighted individuals during monocular viewing.
AB  - OBJECTIVE: To determine the incidence and magnitude of head turn in persons
      unilaterally enucleated at an early age and in normally sighted persons patched
      monocularly. SETTING: The Hospital for Sick Children, Toronto, Ontario.
      PARTICIPANTS: Fifty-two unilaterally enucleated children and adults without
      nystagmus (median age, 10 years) who were enucleated at an early age (median age,
      18 months) due to retinoblastoma and 28 normally sighted children and adults.
      METHODS: Enucleated subjects were videotaped while walking 15 m toward a camera
      under 2 conditions: (1) fixation relaxed (just looking at the camera) and (2)
      fixation forced (trying to identify a small fixation target on the camera).
      Control subjects were tested in the fixation forced condition only. Head turn
      incidence and magnitude were independently rated. Three categories of head turn
      were used: "obvious" (> 10 degrees), "small" (5 degrees-10 degrees), and "no" (0
      degree-4 degrees). RESULTS: In the fixation relaxed condition, 22 (42%) of 52
      enucleated subjects exhibited head turn; when fixation was forced, the incidence
      increased to 25 (58%) of 43 subjects. Head turn was virtually always in the
      direction of the missing eye. Incidence and magnitude of head turn were unrelated
      to age at enucleation or number of years since enucleation. In the control group,
      there was no consistent finding of head turn across subjects when 1 eye was
      patched. CONCLUSIONS: One-eyed children frequently exhibit head turn unrelated to
      the presence of nystagmus. The direction of the head turn is "adaptive" because
      occlusion by the nose in the lower contralateral field is reduced.

PMID- 9194727
TI  - Up-regulation of glial fibrillary acidic protein in the retina of primate eyes
      with experimental glaucoma.
AB  - OBJECTIVE: To identify molecular mechanisms of retinal responses to intraocular
      pressure elevation in primate experimental glaucoma. METHODS: An experimental
      glaucoma model was created by repeated laser trabeculophotocoagulation. After the
      preparation of complementary DNAs from extracted total RNAs in the retinas,
      polymerase chain reaction (PCR) experiments were performed for the following
      screening target genes: beta-tubulin beta 2 and beta 5 and glial fibrillary
      acidic protein (GFAP). To investigate the amplified sequences derived from the
      PCR experiments, sequencing, subcloning, and Southern blot analysis of PCR
      products were performed. In addition, an immunohistochemical analysis was
      performed in an attempt to show the distribution of the target gene products in
      the retinas. RESULTS: A series of PCR experiments suggested up-regulation of gene
      expression for GFAP but not for beta-tubulins. Sequencing of the PCR products and
      results of the Southern blot analysis showed that the amplified sequences were
      derived mainly from the target gene, GFAP, and that increased expression of GFAP
      was found despite the severity of glaucoma. Immunohistochemical studies also
      demonstrated increased expression of GFAP proteins in Muller cells and astrocytes
      in the retinas of primate eyes with experimental glaucoma. CONCLUSIONS: Our study
      showed up-regulation of GFAP at gene and protein levels, which suggests that
      glial components in the retina may contribute to the pathologic processes induced
      by elevated intraocular pressure.

PMID- 9194728
TI  - Retinoblastoma in a dog.
AB  - OBJECTIVE: To describe and classify a retinal tumor found in a dog that
      histologically resembles human retinoblastoma and to discuss the molecular
      mechanisms of retinal oncogenesis. METHODS: A dog eye with a retinal tumor was
      examined histologically. Studies including immunocytochemical analysis for
      retinal S-antigen and glial fibrillary acidic protein, enzyme histochemical
      analysis for carbonic anhydrase, and nick-end DNA labeling were used to
      characterize the tumor. Normal retina from another dog and other tumors from
      dogs, including 2 ciliary body medulloepitheliomas and a brain
      medulloepithelioma, were examined as controls. RESULTS: The retinal tumor
      disclosed characteristics typical of human retinoblastoma, including Flexner
      Wintersteiner rosettes. It showed strong immunoreactivity with S-antigen and
      glial fibrillary acidic protein. Carbonic anhydrase activity also could be shown
      in the tumor. Apoptosis was found to be the predominant method of cell death as
      shown by nick-end DNA labeling. In contrast to the other tumors examined, this
      tumor contained areas with retinal photoreceptor and glial differentiation.
      CONCLUSIONS: The histopathologic findings and differential staining
      characteristics in this retinal tumor are compatible with retinoblastoma, making
      this, to our knowledge, the first documented case of spontaneous retinoblastoma
      in an animal.

PMID- 9194729
TI  - Measurements of vision function and quality of life in patients with cataracts in
      southern India. Report of instrument development.
AB  - OBJECTIVE: To develop and validate vision function (VF) and quality of life (QOL)
      instruments in patients with cataracts in the context of large volume surgery in
      a developing country. MATERIALS AND METHODS: The instruments were developed using
      a consensus approach. One hundred patients who were undergoing cataract surgery
      at Aravind Eye Hospital, Madurai, India, were interviewed preoperatively and 3
      and 12 months postoperatively. Standard clinical procedures were followed,
      including measurement of visual acuity. Between-interviewer reproducibility was
      measured by repeated administration of the preoperative questionnaire. Within
      interviewer reproducibility was measured preoperatively in a separate study of 50
      patients. RESULTS: Preoperative scores from the VF and QOL instruments were
      significantly associated with visual acuity (r = 0.4). Internal reliability
      (Cronbach alpha) was greater than .9. Both instruments showed large changes after
      surgery, with effect sizes of 3 or greater for most VF scales (range, 1.8-3.7)
      and 1 or greater for QOL scales (range, 1.0-2.2). Changes in visual acuity after
      surgery were correlated with changes in the VF (r = 0.44) and QOL (r = 0.41)
      scale scores. Between-interviewer reproducibility was acceptable (total VF scale,
      Spearman r = 0.7; total QOL scale; r = 0.74). The kappa values were lower for
      within-interviewer reproducibility. CONCLUSIONS: The study provided strong
      evidence for the validity, reproducibility, and responsiveness of the
      instruments, and for the feasibility of using them in the setting of a large
      volume of cataract surgery in a developing country.

PMID- 9194731
TI  - Cidofovir.

PMID- 9194730
TI  - Influence of glaucomatous visual field loss on health-related quality of life.
AB  - We examined the influence of glaucomatous visual field defects on vision-targeted
      and generic health-related quality of life. Vision-targeted and generic health
      status were assessed across 5 glaucoma treatment categories and a normal
      reference group from 5 tertiary care ophthalmology practices during regularly
      scheduled eye care visits. The sample consisted of 147 patients who were members
      of specific glaucoma treatment categories and 44 reference group patients. For
      patients with glaucoma, eligibility included a diagnosis of glaucoma at least 1
      year prior to enrollment and no evidence of other eye disease. Participants
      completed 2 vision-targeted surveys, the National Eye Institute Visual
      Functioning Questionnaire and the VF-14, and a generic health-related quality of
      life measure, the Medical Outcomes Study 36-Item Short Form. Data from automated
      perimetry (Humphrey Field Analyzer 24-2, Humphrey Instruments, San Leandro,
      Calif) were used to generate Advanced Glaucoma Intervention Study scores for all
      participants. The Medical Outcomes Study 36-Item Short Form scores from glaucoma
      and reference group participants collected on a random half of the sample were
      similar. However, comparisons of the vision-targeted surveys demonstrated
      significant mean differences on 7 of 11 National Eye Institute Visual Functioning
      Questionnaire scales, and a trend toward significant differences for the VF-14 (P
      < .07 by linear regression). Greater visual field defects in the better eye were
      significantly associated with poorer National Eye Institute Visual Functioning
      Questionnaire scores (P < .05), as well as with worse VF-14 scores. These
      findings were most dramatic for patients with the most severe field loss in the
      better eye. Vision-targeted questionnaires were more sensitive than a generic
      health-related quality of life measure to differences between glaucoma and normal
      reference participants. Our findings indicate that self-reports of vision
      targeted health-related quality of life are sensitive to visual field loss and
      may be useful in tandem with the clinical examination to fully understand
      outcomes of treatment for glaucoma.

PMID- 9194732
TI  - Ultrastructural findings in autosomal dominant drusen.

PMID- 9194733
TI  - Intravitreal invasion of malignant cells from choroidal melanoma after
      brachytherapy.
AB  - We report intravitreal invasion by melanoma cells from a choroidal melanoma after
      brachytherapy. A malignant melanoma of the choroid with collar-button
      configuration was treated with iodine 125 brachytherapy. Years later, the collar
      button developed a dark-chocolate color and began shedding pigmented debris into
      the vitreous. Coalescence of this debris into spheroidal aggregates suggested the
      presence of malignant cells; the eye was enucleated. Histologic sections
      demonstrated a choroidal melanoma with intraretinal and intravitreal invasion by
      melanoma. Clinical evidence of intraretinal invasion by melanoma cells along with
      pigmented debris within the vitreous cavity, especially when clustered in
      spheroidal aggregates, suggests the presence of intravitreal invasion by
      malignant cells. In this case, intravitreal invasion was verified histologically.

PMID- 9194734
TI  - Primary choroidal melanoma in a patient with previous cutaneous melanoma.
AB  - A 67-year-old woman with a history of a skin melanoma that was excised 7 years
      previously had a 6-month history of decreased vision in her right eye. A
      choroidal melanoma was diagnosed clinically, and the eye was enucleated. The
      results of a histopathological examination revealed a primary uveal melanoma.
      Slides of the skin melanoma were obtained, and the initial diagnosis was
      confirmed. In an attempt to illustrate a biological difference between the 2
      melanomas, immunohistochemical studies were performed on sections of the 2
      specimens using S-100 protein, HMB-45, and S-100-beta. Primary cutaneous and
      choroidal melanomas appearing in a patient with no predisposition are rare; this
      is believed to be only the fifth such case reported in the literature.

PMID- 9194735
TI  - Detection of glaucomatous optic disc hemorrhages by confocal scanning laser
      tomography.

PMID- 9194737
TI  - Early reactivation of cytomegalovirus retinitis following placement of a
      ganciclovir implant.

PMID- 9194736
TI  - Hypotony and visual loss with intravenous cidofovir treatment of cytomegalovirus
      retinitis.

PMID- 9194738
TI  - Indocyanine green angiography in Vogt-Koyanagi-Harada-type disease.

PMID- 9194739
TI  - Unilateral pharmacologic mydriasis in a patient with respiratory compromise.

PMID- 9194740
TI  - Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture.
AB  - To our knowledge, there are no articles that describe the specific step-by-step
      details of the surgical removal of premalignant and malignant conjunctival
      tumors. We describe our current approach to the surgical management of squamous
      cell carcinoma (intraepithelial or invasive), localized melanoma, and primary
      acquired melanosis of the conjunctiva. The surgical method differs with limbal
      tumors, extralimbal tumors, and primary acquired melanosis. Limbal lesions are
      managed by localized alcohol corneal epitheliectomy, removal of the main mass by
      a partial lamellar scleroconjunctivectomy, and supplemental cryotherapy. Tumors
      located in the extralimbal conjunctiva are managed by alcohol application, wide
      circumferential surgical resection, and cryotherapy. Primary acquired melanosis
      is managed by alcohol epitheliectomy, removal of suspicious foci, quadrantic
      staging biopsies, and cryotherapy from the underside of the conjunctiva. In all
      cases, a "no touch" method is used and direct manipulation of the tumor is
      avoided to prevent tumor cell seeding into a new area. We have employed this
      technique on 109 patients with conjunctival squamous neoplasms and 137 patients
      with conjunctival melanoma, about 80 of which neoplasms were associated with
      primary acquired melanosis. Our observations suggest that well-planned initial
      surgical management using this technique decreases the chance of tumor recurrence
      for conjunctival melanoma and squamous cell carcinoma. We describe a detailed
      stepwise approach to the surgical management of conjunctival neoplasms. It
      requires meticulous clinical evaluation and complete removal of the tumor in one
      operation using a specific technique.

PMID- 9194741
TI  - Conjunctival epithelial inclusion cyst.

PMID- 9194742
TI  - A case of bilateral cavernous hemangioma associated with intracerebral
      hemangioma.

PMID- 9194743
TI  - Marketing the ophthalmology workforce.

PMID- 9194744
TI  - Outcome of cornea, iris, and lens perforation during automated lamellar
      keratectomy.

PMID- 9194745
TI  - Another possible cause of forceps-induced scratching of a foldable acrylic
      intraocular lens.

PMID- 9194746
TI  - Acute exophthalmos during treatment of a cavernous sinus-dural fistula through
      the superior ophthalmic vein.

PMID- 9194747
TI  - Mesencephalic clefts and eye movement disorders.

PMID- 9194748
TI  - Cellular consequences of the association of apoB lipoproteins with proteoglycans.
      Potential contribution to atherogenesis.
AB  - Many of the discussed results come from empirical experiments performed with in
      vitro models whose relevance to the complex environment of the intima is limited.
      However, they are consistent with the line of reasoning that intima PGs interact
      specifically with apoB lipoproteins and contribute to their retention. This could
      provide the residence time and the initial alterations of the lipoproteins that
      favor their further modifications by oxidative processes and hydrolytic enzymes.
      Products of such modifications, and the modified particles, may be stimuli for
      changes in the functionality of endothelium, smooth muscle cells, and
      macrophages. The focal synthesis of PGs with high affinity for apoB lipoproteins
      could make the phenomena chronic. Clinical and laboratory studies indicate that
      dense LDL, poor in surface polar lipids, is associated with an atherogenic
      phenotype. Particles with these properties may contribute to the disease via its
      high affinity for arterial PGs. This affinity can be modulated by diet,
      lifestyle, and lipid-lowering drugs.

PMID- 9194749
TI  - Endothelial permeability for macromolecules. Mechanistic aspects of
      pathophysiological modulation.

PMID- 9194750
TI  - Acetylated LDL endocytosis by the human monocytic Mono Mac 6sr cells is not
      mediated by the macrophage type I and II scavenger receptors.
AB  - We recently reported that the human monocytic Mono Mac 6sr cell line
      constitutively takes up and degrades acetylated (acLDL) and oxidized LDL through
      receptor-specific pathways. The present studies were undertaken to further
      characterize the acLDL binding site on a functional and molecular basis. The
      degradation of acLDL increased during differentiation of Mono Mac 6sr cells with
      lipopolysaccharide (10 ng/mL, 72 hours) and low concentrations of phorbol 12
      myristate 13-acetate (PMA; 0.1 to 1.0 ng/mL, 72 hours). Higher doses of PMA (5 or
      10 ng/mL), however, decreased acLDL degradation. Scatchard plots of acLDL binding
      in untreated and LPS-differentiated Mono Mac 6sr cells were nonlinear and
      suggested the presence of more than one binding site. Although the ligand
      specificity of the acLDL receptor in Mono Mac 6sr cells resembles that of the
      macrophage type I and type II scavenger receptors, we did not detect mRNA of
      either receptor type in untreated or differentiated Mono Mac 6sr cells by means
      of Northern blotting and reverse transcription polymerase chain reaction.
      Furthermore, ligand blotting with 125I-acLDL failed to detect the 220-kD types I
      and II scavenger receptor protein. Thus, Mono Mac 6sr cells express an acLDL
      receptor that is distinct from the type I and type II scavenger receptor found in
      human monocyte-derived macrophages but that, like the latter, is induced during
      monocytic differentiation.

PMID- 9194751
TI  - Organ loci of catabolism of short truncations of apoB.
AB  - Truncations of apolipoprotein (apo) B shorter than 3200 amino acids (3200/4536 =
      apoB-70) do not possess the LDL receptor-recognition domain and are not
      recognized by altered cells with normally functioning LDL receptors. To ascertain
      which organs remove such truncated apoB-containing particles, we isolated apoB-31
      , apoB-38.9-, and apoB-43.7-containing particles from plasmas of familial
      hypobetalipoproteinemia heterozygous humans by a combination of sequential
      ultracentrifugation and preparative electrophoresis. Particles with labeled 125I-
      or 131I-dilactitol tyramine (I-DLT), were injected into New Zealand White
      rabbits, along with I-DLT-apoB-100-containing LDLs, and the decay of 125I- and
      131I-TCA-precipitated counts was followed over 24 hours. At the end of 24 hours,
      rabbits were anesthetized and their bodies perfused. Organs were removed and
      homogenized, and TCA-precipitable counts determined. Fractional catabolic rates
      of apoB truncation particles were two to five times greater than those of apoB
      100 LDLs. ApoB truncations accumulated in adrenals at one fifth the rates of apoB
      100 LDL, compatible with the functional absences of LDL receptor-recognition
      domains in truncated apoBs. The major organ of uptake for apoB-100-LDLs was the
      liver, whereas truncation particles were readily removed by the kidney (kidney:
      liver uptake ratios were 0.10 to 0.30 for apoB-100 LDLs and 1.03 to 3.77 for
      truncations). Spleens accumulated little of either apoB-100 or truncation
      particles, suggesting particles were not "damaged" or aggregated. Thus, the
      absence of > 56% of the carboxyl end of apoB-100 increases the plasma clearance
      and redirects the organ uptake of the apoB truncation-containing lipoproteins
      from liver to kidney.

PMID- 9194752
TI  - Codon 54 polymorphism of the human intestinal fatty acid binding protein 2 gene
      is associated with dyslipidemias but not with insulin resistance in patients with
      familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is associated with variable expression of
      dyslipidemias and insulin resistance. In nondiabetic Pima Indians an A to G
      substitution in codon 54 of the fatty acid binding protein 2 (FABP2) gene has
      been shown to be associated with insulin resistance. We screened the entire
      coding region of this gene by single-strand conformation polymorphism analysis in
      24 probands (17 men and 7 women; age, 63.0 +/- 7.4 years [mean +/- SD]; body mass
      index [BMI], 27.7 +/- 4.2 kg/m2) who had FCHL and in 40 healthy men from a random
      population sample of 82 men (age, 54.0 +/- 5.0 years; BMI, 26.3 +/- 3.2 kg/m2).
      Insulin resistance was assessed with the euglycemic clamp in 58 subjects from
      FCHL families (14 probands with FCHL and 44 first-degree relatives of probands;
      38 men and 20 women; age, 51.5 +/- 12.6 years; BMI, 25.5 +/- 3.9 kg/m2). We found
      three nucleotide substitution in the FABP2 gene: GCT to ACT (Ala-->Thr) in codon
      54, GTA to GTG in codon 118, and GCGCA to GCACA in the 3'-noncoding region.
      Frequencies of these variants did not differ between the patients and control
      subjects. The Ala to Thr substitution in codon 54 was associated with a high
      lipid oxidation rate (P = .011 after adjustment for sex and family relationship),
      high HDL triglycerides (P = .042), and high LDL triglycerides (P = .013) but not
      with insulin resistance in subjects from FCHL families. The FABP2 gene is
      unlikely to be a major gene for FCHL, but it might affect lipid metabolism in
      subjects with FCHL.

PMID- 9194753
TI  - Cholesteryl ester transfer protein activity enhances plasma cholesteryl ester
      formation. Studies in CETP transgenic mice and human genetic CETP deficiency.
AB  - The plasma cholesteryl ester transfer protein (CETP) promotes the removal of HDL
      cholesteryl esters and is thought to stimulate reverse cholesterol transport
      (RCT). However, mechanisms by which CETP may stimulate RCT are poorly understood.
      Thus, we examined the relationship between plasma CETP expression and plasma
      cholesteryl ester formation in CETP transgenic (Tg) mice, hamsters, and human
      subjects with genetic CETP deficiency. Incubation of CETP Tg mouse plasma showed
      a 20% to 40% increase in plasma cholesterol esterification rate (CER, P < .05)
      compared with control mice. Injection of a neutralizing CETP monoclonal antibody
      (MAb) (TP2) into natural flanking region CETP Tg mice resulted in an increase in
      plasma free cholesterol (FC) concentration, FC/CE ratio, FC/phosphatidylcholine
      ratio, and hepatic CETP mRNA. In hamsters, CETP inhibition also resulted in an
      increase in plasma FC/phosphatidylcholine ratio and increased CETP mRNA in
      adipose tissue. In humans with two common CETP gene mutations (an intron 14
      splicing defect and a D442G missense mutation), mean plasma CERs were 39 and 60,
      respectively, compared with 89 nmol x mL-1 x h-1 in normal subjects. By contrast,
      lecithin:cholesterol acyltransferase (LCAT) mass was normal in CETP-deficient
      subjects. MAb neutralization of CETP activity in incubated human plasma did not
      alter the LCAT reaction, even after supplementation with discoidal HDL and VLDL.
      Thus, genetic alterations in CETP levels lead to secondary changes in the plasma
      LCAT reaction, possibly because of remodeling of HDL by CETP acting in concert
      with other factors in vivo. In human genetic CETP deficiency, a moderate
      impairment in the plasma LCAT reaction may contribute to a defect in RCT,
      providing a potential mechanism to explain the recently observed excess of
      coronary heart disease in these subjects.

PMID- 9194754
TI  - Genetic cholesteryl ester transfer protein deficiency is extremely frequent in
      the Omagari area of Japan. Marked hyperalphalipoproteinemia caused by CETP gene
      mutation is not associated with longevity.
AB  - Low levels of HDL cholesterol have been clearly demonstrated to be associated
      with an increased incidence of coronary heart disease, strongly suggesting that
      HDL particles have an antiatherogenic function. However, little information has
      been available concerning the atherogenicity of a marked
      hyperalphalipoproteinemia (HALP). There is no agreement about whether plasma
      cholesteryl ester transfer protein (CETP) deficiency is associated with an
      antiatherogenic state or not, although this disorder was reported to be one of
      the major causes of marked HALP. In the current study, we have found a unique
      area (Omagari City, Akita Prefecture, Japan) where CETP deficiency caused by a G
      to-A mutation at the 5' splice donor site of intron 14 in the CETP gene is
      extremely frequent. In Omagari City, the mutation was detected more than 20 times
      more frequently and the prevalence of a marked HALP with plasma HDL cholesterol >
      or = 2.58 mmol/L (100 mg/dL) was 5 to 10 times higher than in other areas of
      Japan. This discovery has made it possible to perform a large population-based
      study concerning the atherogenicity of a marked elevation of HDL cholesterol in a
      genetically more homogeneous population. There was a statistically significant U
      shaped relationship between HDL cholesterol levels and the incidence of ischemic
      changes in electrocardiograms. In cases of HDL cholesterol < 1.81 mmol/L (70
      mg/dL), the incidence increased in proportion to the levels of HDL cholesterol.
      The frequency of the CETP gene mutation was higher in patients with coronary
      heart disease than in healthy control subjects. In subjects aged > 80 years, the
      prevalence of both marked HALP and the intron 14 splicing defect was
      significantly lower than in the younger generation. The current study indicated
      for the first time that a marked HALP caused by CETP gene mutation may not
      represent a longevity syndrome, suggesting the importance of reevaluation of the
      clinical significance and pathophysiology of a marked HALP.

PMID- 9194755
TI  - Common genomic variants associated with variation in plasma lipoproteins in young
      aboriginal Canadians.
AB  - We hypothesized that common genomic variants would be associated with variation
      in lipoprotein phenotypes in young subjects. We determined genotypes of FABP2,
      PON, APOC3, and APOE in 188 aboriginal Canadians, aged 9 to 17 years. We found
      that 13 of 32 possible genotype-phenotype associations were significant: (1) the
      FABP2 codon 54 genotype was associated with variation in plasma triglycerides (P
      = .045); (2) the PON codon 192 genotype was associated with variation in plasma
      total and LDL cholesterol and apoB (P = .0099, P = .0088, and P = .016,
      respectively); (3) the APOC3 insulin-response-element genotype was associated
      with variation in plasma triglycerides, HDL cholesterol, apoA-I, the total
      cholesterol to HDL cholesterol ratio, and the apoB to apoA-I ratio (P = .0014, P
      = .0069, P = .045, P = .0021, and P = .0081, respectively); and (4) the APOE
      restriction isotype was associated with variation in plasma LDL cholesterol,
      apoB, the total cholesterol to HDL cholesterol ratio, and the apoB to apoA-I
      ratio (P = .025, P = .034, P = .045, and P = .047, respectively). The average
      young age and relative absence of age-dependent secondary environmental factors
      could have eased the identification of small genetic effects on lipoprotein
      phenotypes in this study sample.

PMID- 9194756
TI  - Genetic polymorphism of paraoxonase and the risk of coronary heart disease.
AB  - Recent studies have implicated paraoxonase, an HDL-associated enzyme, in
      providing protection against LDL oxidation, thus affecting the risk of coronary
      heart disease (CHD) in the general population. In this study, we evaluated the
      distribution of a biallelic PON polymorphism at codon 192 (A and B alleles) and
      its relationship with plasma lipids and CHD in two racial groups comprising Asian
      Indians and Chinese from Singapore. The frequency of the B allele was
      significantly higher in Chinese control subjects than in Indian control subjects
      (0.58 versus 0.33; P < .0001). With the exception of a marginal effect on
      apolipoprotein A-I levels in Indians, no other significant association was
      observed between the PON polymorphism and quantitative lipid traits in either
      racial group. However, there was a race-specific association of the B allele with
      CHD in Indians but not in Chinese. The Indian CHD patients had a significantly
      higher frequency of the B allele than control subjects (.43 versus .33; P =
      .014). The age- and sex-adjusted odds ratio for developing CHD with the B allele
      (BB+AB genotypes) was 2.01 (95% CI, 1.17 to 3.45; P = .011) compared with the A
      allele (AA genotype). When the Indian patients were stratified into subgroups,
      the association remained significant in nondiabetic patients (odds ratio, 2.29; P
      = .008), and it became stronger in patients with myocardial infarction (odds
      ratio, 2.94; P = .004) than in patients without myocardial infarction (odds
      ratio, 1.11; P = .76). These data indicate that a common polymorphism in the PON
      gene is an independent risk factor for CHD in populations with white ancestry.

PMID- 9194757
TI  - Urbanization elicits a more atherogenic lipoprotein profile in carriers of the
      apolipoprotein A-IV-2 allele than in A-IV-1 homozygotes.
AB  - Coronary heart disease (CHD) is increasing in developing countries, particularly
      in urban areas. The impact of urbanization and apolipoprotein (apo) A-IV genetic
      polymorphism on plasma lipoproteins was studied in 222 men and 236 women from
      rural and urban Costa Rica. The apoA-IV allele frequencies were 0.937 for apoA-IV
      1 and 0.062 for apoA-IV-2, Significant interactions between the apoA-IV
      polymorphism and area of residence (rural versus urban) were detected for HDL
      cholesterol (P = .003), apoA-I (P = .05), LDL particle size (P = .01), and
      LDL/HDL cholesterol ratio (P = .005). Urban compared with rural carriers of the
      apoA-IV-2 allele had significantly lower plasma HDL cholesterol (0.95 versus 1.17
      mmol/L) and apoA-I (980 versus 1140 mg/L), a significantly higher LDL/HDL
      cholesterol ratio (3.35 versus 2.39), and significantly smaller LDL particles
      (258 versus 263 A). In contrast, no significant rural-urban differences for these
      parameters were found in apoA-IV-1 homozygotes. Regardless of their apoA-IV
      phenotype, urban residents consumed more saturated fat (P = .02) and smoked more
      cigarettes per day (P = .03) than rural residents. A significant interaction
      between saturated fat intake and apoA-IV phenotype was found for HDL cholesterol
      (P < .0003) and LDL/HDL cholesterol ratio (P < .003). Increased saturated fat
      intake (13.6% versus 8.6% of calories) was significantly associated with 6%
      higher HDL cholesterol and no change (0.7%) in LDL/HDL cholesterol ratio in apoA
      IV-1 homozygotes and with 19% lower HDL cholesterol and 37% higher LDL/HDL
      cholesterol ratio among carriers of the apoA-IV-2 allele. Smokers (> or = 1
      cigarette per day) had significantly lower HDL cholesterol (P < .005) and apoA-I
      (P < .01) concentrations than nonsmokers (< 1 cigarette per day), particularly
      among carriers of the apoA-IV-2 allele (-19% and -13%) compared with apoA-IV-1 (
      4% for both). After taking these lifestyle characteristics into account, the
      areas of residence by phenotype interactions for plasma lipoprotein
      concentrations were no longer statistically significant. Lifestyles associated
      with an urban environment, such as increased smoking and saturated fat intake,
      elicit a more adverse plasma lipoprotein profile among Costa Rican carriers of
      the apoA-IV-2 allele than in apoA-IV-1 homozygotes. Therefore, under the
      conditions studied, persons with the apoA-IV-2 allele may be more susceptible to
      CHD.

PMID- 9194758
TI  - Associations of age, adiposity, menopause, and alcohol intake with low-density
      lipoprotein subclasses.
AB  - We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the
      associations of age, adiposity, menopause, and alcohol intake with LDL subclasses
      in 355 individuals. The absorbency of protein stain was used as an index of mass
      concentrations at intervals of 0.05 nm within seven LDL subclasses: LDL-IVB (22.0
      to 23.2 nm), LDL-IVA (23.3 to 24.1 nm), LDL-IIIB (24.2 to 24.6 nm), LDL-IIIA
      (24.7 to 25.5 nm), LDL-II (25.5 to 26.4 nm), LDL-I (26.0 to 28.5 nm), and
      intermediate-size lipoproteins (ISL, 28.0 to 32.0 nm). Age and alcohol intake
      were obtained from questionnaires, and body mass index was computed from clinic
      measurements of weight and height. In adult men, body mass index correlated
      positively with LDL-III, and alcohol intake correlated positively with larger LDL
      I. Age was positively correlated with LDL-IIIA and ISL in both men and women and
      with LDL-IIIB and LDL-II in women. Postmenopausal women had higher LDL-IIIA, LDL
      II, and ISL than both premenopausal and premenarchal females. Adult males, > or =
      18 years old, had higher levels of LDL-IIIA and LDL-II than younger males.
      Adjustment for fasting plasma triglyceride levels eliminated the significant
      associations between age and LDL-IIIA in both men and women and between age and
      LDL-II in women. Partial correlation analyses showed that reductions in the LDL
      peak diameter associated with increasing age, male sexual maturation, menopause,
      and adiposity are attributable to increases in the LDL-IIIA subclass. Thus,
      densitometric measurements of protein-stained gradient gels reveal specific
      relationships between LDL subclasses and age, adiposity, and alcohol intake
      beyond those identified by the LDL peak or average diameter.

PMID- 9194760
TI  - Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men.
      Prospective results from the Quebec Cardiovascular Study.
AB  - Individuals with elevated plasma concentrations of HDL cholesterol are at lower
      risk for ischemic heart disease (IHD). Whether the cardioprotective effects of
      HDL can be attributed to one or both HDL subfractions (HDL2 and HDL3) remains,
      however, controversial. The relationship of HDL subfractions to the incidence of
      IHD was investigated in a sample of 1169 French-Canadian men younger than 60
      years and living in the Quebec City suburbs. Between 1980 to 1981 and 1990, 83 of
      the 944 men with complete follow-up in 1990 (80.8%) had a first IHD. Men who
      developed IHD had lower HDL, HDL2, and HDL3 cholesterol concentrations at
      baseline than men who remained free from IHD. Adjusted relative risk (RR) of IHD
      was calculated among quartiles of HDL cholesterol and HDL subfractions with the
      use of Cox survival models. Men in the fourth quartile of HDL2 (RR = 0.21; 95%
      confidence interval [CI], 0.08 to 0.56) and HDL3 cholesterol distributions (RR =
      0.37; 95% CI, 0.15 to 0.94) were at lower risk for IHD than men in the first
      quartile. Despite the fact that the respective contributions of HDL2 and HDL3 to
      IHD risk were of the same magnitude in a multivariate model that included both
      subfractions, the contribution of the HDL2 subfraction was statistically
      significant (standardized RR = 0.84; 95% CI, 0.74 to 0.95), whereas it did not
      reach significance for HDL3 (standardized RR = 0.87; 95% CI, 0.69 to 1.11).
      Neither the linear combination of HDL2 and HDL3 nor their ratio provided further
      information on the risk of IHD compared with HDL cholesterol alone or with the
      ratio of total to HDL cholesterol. From a statistical standpoint, the present
      data suggest that the HDL2 subfraction may be more closely related to the
      development of IHD than the HDL3 subfraction. However, the qualitative difference
      in the relative predictive value of each subfraction was trivial, since it only
      corresponded to a modest quantitative difference. Thus, the possibility that a
      significant proportion of the cardioprotective effect of elevated HDL cholesterol
      levels may be mediated by the HDL3 subfraction still cannot be excluded. Finally,
      from a clinical point of view and within the limits of resolution provided by
      these data, the measurement of HDL subfractions does not appear to provide any
      additional information on the risk of IHD than HDL cholesterol alone or the ratio
      of total to HDL cholesterol.

PMID- 9194759
TI  - Alcohol increases plasma levels of cholesterol diet-induced atherogenic
      lipoproteins and aortic atherosclerosis in rabbits.
AB  - The purpose of the present study was to reexamine the relationship between
      alcohol and atherosclerosis. Two experiments were performed: The first contained
      three groups of New Zealand White (NZW) female rabbits. The control group was fed
      a cholesterol-containing liquid diet and the other two groups were fed the same
      diet with either 20% or 30% of the calories supplied by alcohol. The second
      experiment had two treatments: one control group and another group fed a 10%
      alcohol diet. In experiment 1, alcohol at the 20% and 30% levels increased VLDL
      and LDL but not HDL compared with levels in control rabbits. Hepatic mRNA levels
      of apolipoprotein (apo) A-I, apoB, and 7 alpha-hydroxylase were not affected by
      alcohol. However, the LDL-receptor mRNA was decreased to half of control values
      by either 20% or 30% alcohol. Lesion areas and aortic cholesterols were
      significantly increased in the 20% and 30% alcohol-treated groups. Also,
      significant correlations were found between plasma cholesterol levels and total
      lesion area or lesion cholesterol contents. In experiment 2, the 10% alcohol
      treated rabbits showed no differences in circulating lipoproteins, LDL-receptor
      mRNA, or lesion formation above that observed in controls. These experiments
      suggest that alcohol substituted at 20% or 30% of the dietary calories induces
      hypercholesterolemia and more aortic atherosclerotic lesions. The alcohol-induced
      accumulation of VLDL and LDL was accompanied by low hepatic LDL-receptor mRNA
      levels, suggesting that alcohol may affect LDL-receptor expression and rates of
      lipoprotein clearance, but more experiments are needed to evaluate this
      possibility.

PMID- 9194761
TI  - Fibrinolytic activity is similar in physically active men with and without a
      history of myocardial infarction.
AB  - The purpose of this study was to evaluate fibrinolytic potential at rest and
      after a fibrinolytic stressor in men with a history of myocardial infarction (MI)
      compared with an age- and activity-matched group of men without coronary artery
      disease (CAD). All men were currently enrolled in exercise programs. Tissue-type
      plasminogen activator (TPA) and plasminogen activator inhibitor 1 (PAI-1)
      activity and antigen levels were measured at rest and after a maximal exercise
      test. A 2 x 2 (group x time) ANOVA with repeated measures was used to evaluate
      fibrinolytic potential. Bivariate regressions were conducted to evaluate
      relations between fibrinolytic potential and maximal oxygen uptake (VO2max). Age
      was similar between groups (CAD, 57.5 +/- 6.6; non-CAD, 58.1 +/- 7.3 years);
      however, VO2max was higher in non-CAD subjects (36.2 +/- 6.2 vs 27.5 +/- 5.9
      mL.kg-1.min-1). Mean +/- SEM resting TPA and PAI-1 activities were similar
      between CAD and non-CAD subjects (TPA, 2.8 +/- 0.2 vs 2.8 +/- 0.2 IU/mL; PAI-1,
      15.9 +/- 3.1 vs 13.1 +/- 4.1 AU/mL). Both groups showed similar significant
      increases in TPA activity with exercise (P < .05), and postexercise TPA activity
      was also similar (CAD, 9.1 +/- 2.0 IU/mL; non-CAD, 11.7 +/- 2.6 IU/mL). Both
      groups also showed similar significant decreases in PAI-1 activity with exercise
      (P < .05) and no differences in postexercise PAI-1 activity (CAD, 13.2 +/- 2.5
      AU/mL; non-CAD, 10.4 +/- 3.6 AU/mL). Significantly higher resting TPA antigen
      levels were seen in CAD (14.8 ng/mL) than non-CAD (10.2 ng/mL) subjects (P <
      .05), but neither group showed significant changes with exercise (CAD, 12.9
      ng/mL; non-CAD, 11.8 ng/mL). Resting PAI-1 antigen was similar in the two groups
      (CAD, 71.4 ng/mL; non-CAD, 74.2 ng/mL) and did not significantly change with
      exercise (CAD, 77.9 ng/mL; non-CAD, 72.3 ng/mL). VO2max was positively correlated
      with postexercise TPA activity (r = .52, P < .05) and negatively correlated with
      resting TPA antigen (r = -.43, P < .05). Resting TPA antigen was also directly
      correlated with body mass index (r = .63, P < .05). The finding that functional
      fibrinolytic activity was not different in physically active men with and without
      CAD contrasts with previous reports. This suggests that matching subjects on the
      bases of age and habitual physical activity status and controlling exercise
      intensity are important factors to consider when evaluating fibrinolytic
      potential.

PMID- 9194762
TI  - Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of
      ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study.
AB  - High triglyceride (TG) and low HDL cholesterol (HDL-C) is the characteristic
      dyslipidemia seen in insulin-resistant subjects. We examined the role of this
      dyslipidemia as a risk factor of ischemic heart disease (IHD) compared with that
      of high LDL cholesterol (LDL-C) in the Copenhagen Male Study. In total 2910 white
      men, aged 53 to 74 years, free of cardiovascular disease at baseline, were
      subdivided into four groups on the basis of fasting concentrations of serum TG,
      HDL-C, and LDL-C. "High TG-low HDL-C" was defined as belonging to both the
      highest third of TG and the lowest third of HDL-C; this group encompassed one
      fifth of the population. "High LDL-C" was defined as belonging to the highest
      fifth of LDL-C. A control group was defined as not belonging to either of these
      two groups. "Combined dyslipidemia" was defined as belonging to both dyslipidemic
      groups. Age-adjusted incidence of IHD during 8 years of follow-up was 11.4% in
      high TG-low HDL-C, 8.2% in high LDL-C, 6.6% in the control group, and 17.5% in
      combined dyslipidemia. Compared with the control group, relative risks of IHD
      (95% confidence interval), adjusted for potentially confounding factors or
      covariates (age, body mass index, alcohol consumption, physical activity, non
      insulin-dependent diabetes, hypertension, smoking, and social class), were 1.5
      (1.0-2.1), P < .05; 1.3 (0.9-2.0), P = .16; and 2.4 (1.5-4.0), P < .01, in the
      three dyslipidemic groups, respectively. In conclusion, the present results
      showed that high TG-low HDL-C, the characteristic dyslipidemia seen in insulin
      resistant subjects, was at least as powerful a predictor of IHD as isolated high
      LDL-C. The results suggest that efforts to prevent IHD should include
      intervention against high TG-low HDL-C, and not just against
      hypercholesterolemia.

PMID- 9194763
TI  - Relationship of C-reactive protein to risk of cardiovascular disease in the
      elderly. Results from the Cardiovascular Health Study and the Rural Health
      Promotion Project.
AB  - Markers of inflammation, such as C-reactive protein (CRP), are related to risk of
      cardiovascular disease (CVD) events in those with angina, but little is known
      about individuals without prevalent clinical CVD. We performed a prospective,
      nested case-control study in the Cardiovascular Health Study (CHS; 5201 healthy
      elderly men and women). Case subjects (n = 146 men and women with incident CVD
      events including angina, myocardial infarction, and death) and control subjects
      (n = 146) were matched on the basis of sex and the presence or absence of
      significant subclinical CVD at baseline (average follow-up, 2.4 years). In women
      but not men, the mean CRP level was higher for case subjects than for control
      subjects (P < or = .05). In general, CRP was higher in those with subclinical
      disease. Most of the association of CRP with female case subjects versus control
      subjects was in the subgroup with subclinical disease; 3.33 versus 1.90 mg/L, P <
      .05, adjusted for age and time of follow-up. Case-control differences were
      greatest when the time between baseline and the CVD event was shortest. The
      strongest associations were with myocardial infarction, and there was an overall
      odds ratio for incident myocardial infarction for men and women with subclinical
      disease (upper quartile versus lower three quartiles) of 2.67 (confidence
      interval [CI] = 1.04 to 6.81), with the relationship being stronger in women
      (4.50 [CI = 0.97 to 20.8]) than in men (1.75 [CI = 0.51 to 5.98]). We performed a
      similar study in the Rural Health Promotion Project, in which mean values of CRP
      were higher for female case subjects than for female control subjects, but no
      differences were apparent for men. Comparing the upper quintile with the lower
      four, the odds ratio for CVD case subjects was 2.7 (CI = 1.10 to 6.60). In
      conclusion, CRP was associated with incident events in the elderly, especially in
      those with subclinical disease at baseline.

PMID- 9194764
TI  - Effects of short-term hormone replacement therapies on low-density lipoprotein
      metabolism in cynomologus monkeys.
AB  - Estrogen replacement therapy reduces the risk of coronary heart disease in women
      and decreases the extent of atherosclerosis in monkeys. In our previous studies,
      estrogen treatment decreased arterial LDL degradation and accumulation, thus
      indicating one mechanism by which estrogen inhibits the progression of
      atherosclerosis. The influence of progestins on these processes remains nuclear.
      The objective of this study was to determine the effects of oral estrogen
      (conjugated equine estrogens) and progestin (medroxyprogesterone acetate) alone
      or in combination on arterial LDL metabolism after 12 weeks of atherogenic
      stimulus. This relatively short period of treatment was chosen to determine
      effects on arterial LDL metabolism before substantial subendothelial macrophage
      accumulation. In contrast to previous studies (16 to 18 weeks of treatment), when
      macrophages were present in the intima, neither estrogen nor progestin (nor their
      combination) had any effect on any index of arterial LDL metabolism. These
      results suggest that estrogen may preferentially reduce LDL metabolism in
      macrophages with little effect on cells of the normal artery. In contrast to
      arterial LDL metabolism, hepatic LDL uptake was significantly increased in
      animals treated with estrogen or estrogen plus progestin. Despite the increased
      LDL uptake by the liver, hepatic lipid content was significantly decreased by
      approximately 50% in both estrogen and estrogen-plus-progestin treatment compared
      with control and progestin-treated animals. The decrease in hepatic cholesterol
      content in hypothesized to be due to increased biliary secretion of cholesterol.

PMID- 9194765
TI  - Parathyroid hormone-related peptide as a local regulator of vascular
      calcification. Its inhibitory action on in vitro calcification by bovine vascular
      smooth muscle cells.
AB  - In the present study, we investigated the role of parathyroid hormone-related
      peptide (PTHrP) in vascular calcification by using an in vitro calcification
      model. We demonstrated that the expression of PTHrP decreased in the progression
      of bovine vascular smooth muscle cell (BVSMC) calcification and that inhibition
      of calcification by etidronate (EHDP) and levamisole restored PTHrP secretion,
      suggesting that the expression of PTHrP is associated with calcification. PTHrP
      (1-34) and PTH (1-34) dose-dependently inhibited BVSMC calcification. Protein
      kinase A (PKA) and protein kinase C (PKC) inhibitors completely blocked the
      inhibitory effect of PTHrP, suggesting that both PKA and PKC may be involved in
      its signaling pathway. Moreover, PTHrP inhibited alkaline phosphatase (ALP)
      activity, implying that the impact on ALP may contribute to its action on
      calcification. Furthermore, the PTHrP antagonist, PTHrP (7-34), dose-dependently
      increased calcium deposition by BVSMC. Interestingly, PTHrP production by BVSMC
      dramatically increased in the presence of EHDP, and PTHrP (7-34) partially
      antagonized the inhibitory effect of EHDP on BVSMC calcification. These results
      suggest that PTHrP may regulate vascular calcification as an autocrine/paracrine
      factor.

PMID- 9194766
TI  - Glucocorticoids stimulate cholesteryl ester formation in human smooth muscle
      cells.
AB  - The aim of the present study was to investigate the effect of synthetic
      glucocorticoid dexamethasone (Dex) on cholesterol esterification in cultured
      human smooth muscle cells (SMC). In labeled SMC, Dex stimulated the
      esterification of [3H]cholesterol in a dose-dependent manner. This effect was
      specific for glucocorticoid hormones and could be inhibited by cycloheximide (3
      ng/mL), actinomycin D (10(-5) mol/L), and the specific glucocorticoid antagonist
      RU 486 (10(-8) mol/L). When plasma membrane was selectively labeled with trace
      quantities of [3H]cholesterol (0.25 microCi/mL, 1 hour, 10 degrees C), Dex (10(
      8) mol/L) caused a net flux of free [3H]cholesterol into the cells. Moreover, Dex
      (10(-8) mol/L, 24 hours) stimulated the esterification of sterols, newly
      synthesized from [14C]mevalonate (10 microCi/mL, 4 hours) and lowered the amount
      of [14C]sterols susceptible for cholesterol oxidase. The incorporation of
      [14C]oleic acid into cholesteryl esters was markedly higher in Dex-pretreated SMC
      than in the control cells (2.1 +/- 0.07 and 1.4 +/- 0.1 pmol/h/microgram protein,
      respectively, P < .01). At the time, cholesteryl ester hydrolysis in Dex-treated
      cells was reduced (72 +/- 8 pmol cholesteryl esters/h per milligram versus 130 +/
      10 in the control cells). HDL3-mediated [3H]cholesterol efflux was also
      inhibited in Dex-treated cells; moreover, HDL3 (40 micrograms/mL, 24 hours) had
      practically no effect on [3H]cholesteryl ester content in Dex-treated SMC but
      caused a 50% reduction of [3H]cholesteryl esters in the control cells. Thus, in
      human SMC glucocorticoids alter the redistribution of cholesterol between the
      pools of free and esterified cholesterol, paralleled by the change in acyl
      coenzyme A: cholesteryl acyltransferase and neutral cholesteryl ester hydrolase
      activities, leading to the impaired HDL3-mediated cholesterol efflux.

PMID- 9194767
TI  - Prevention of aortic fibrosis by spironolactone in spontaneously hypertensive
      rats.
AB  - We have previously shown that long-term angiotensin-converting enzyme (ACE)
      inhibition prevents the increase in aortic collagen in spontaneously hypertensive
      rats (SHRs), independent of blood pressure reduction. More recently, we reported
      that the effects of ACE inhibition in the prevention of aortic collagen
      accumulation were related to the inhibition of angiotensin II actions on
      angiotensin II type 1 receptors. Aldosterone, the synthesis of which is mainly
      modulated by angiotensin II through type 1 receptor stimulation, is known to
      promote cardiac fibrosis in different experimental models. The aim of the present
      study was to determine whether inhibition of aldosterone formation was able to
      prevent aortic fibrosis in SHRs. For this purpose, we compared the effects of a 4
      month treatment with the aldosterone antagonist spironolactone with the ACE
      inhibitor quinapril in 4-week-old SHRs. Control SHRs and Wistar-Kyoto (WKY) rats
      received placebo for the same period of time. At the end of treatment, in
      conscious SHRs vs WKY controls, quinapril completely prevented the development of
      hypertension, whereas spironolactone produced only a slight but significant
      reduction in blood pressure. Aortic hypertrophy was significantly prevented by
      ACE inhibition but not by spironolactone. On the contrary, aortic collagen
      accumulation was completely prevented by both quinapril and spironolactone. In
      the latter case, collagen density was significantly below that of WKY controls.
      These results show that in SHRs, spironolactone can markedly prevent aortic
      fibrosis in the presence of a very slight antihypertensive effect. It is
      suggested that ACE inhibition or type 1 receptor antagonist-induced prevention of
      aortic collagen accumulation is at least partially related to aldosterone
      inhibition.

PMID- 9194768
TI  - The effects of folic acid supplementation on plasma total homocysteine are
      modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes.
AB  - Elevated concentration of plasma total homocysteine (tHcy) is a common risk
      factor for arterial occlusive diseases. Folic acid (FA) supplementation usually
      lowers tHcy levels, but initial tHcy and vitamin levels, multivitamin use, and
      polymorphisms in the gene for 5, 10-methylenetetrahydrofolate reductase (MTHFR)
      may contribute to variability in reduction. We tested the effects of a 3-week
      daily intake of 1 or 2 mg of FA supplements on tHcy levels in patients with and
      without coronary heart disease (CHD) who were analyzed for the C677T MTHFR
      mutation. Prior multivitamin intake and baseline vitamin and tHcy levels were
      also compared with responsiveness to folate supplementation. Both dosages of FA
      lowered tHcy levels similarly, regardless of sex, age, CHD status, body mass
      index, smoking, or plasma creatinine concentration. In non-multivitamin users, FA
      supplements reduced tHcy by 7% in C/C homozygotes and by 13% or 21% in subjects
      with one or two copies of the T677 allele, respectively; the corresponding
      reductions were smaller in users of multivitamins. Moreover, T/T homozygotes had
      elevated tHcy and increased susceptibility to high levels of tHcy at marginally
      low plasma folate levels, as well as enhanced response to the tHcy-lowering
      effects of FA. Although other factors are probably involved in the responsiveness
      of tHcy levels to FA supplementation, about one third of heterogeneity in
      responsiveness was attributable to baseline tHcy and folate levels and to
      multivitamin use.

PMID- 9194769
TI  - Arterial compliance in obese subjects is improved with dietary plant n-3 fatty
      acid from flaxseed oil despite increased LDL oxidizability.
AB  - The compliance or elasticity of the arterial system, an important index of
      circulatory function, diminishes with increasing cardiovascular risk. Conversely,
      systemic arterial compliance improves through eating of fish and fish oil. We
      therefore tested the value of high intake of alpha-linolenic acid, the plant
      precursor of fish fatty acids. Fifteen obese people with markers for insulin
      resistance ate in turn four diets of 4 weeks each; saturated/high fat (SHF),
      alpha-linolenic acid/low fat (ALF), oleic/low fat (OLF), and SHF. Daily intake of
      alpha-linolenic acid was 20 g from margarine products based on flax oil. Systemic
      arterial compliance was calculated from aortic flow velocity and aortic root
      driving pressure. Plasma lipids, glucose tolerance, and in vitro LDL
      oxidizability were also measured. Systemic arterial compliance during the first
      and last SHF periods was 0.42 +/- 0.12 (mean +/- SD) and 0.56 +/- 0.21 units
      based on milliliters per millimeter of mercury. It rose significantly to 0.78 +/-
      0.28 (P < .0001) with ALF; systemic arterial compliance with OLF was 0.62 +/-
      0.19, lower than with ALF (P < .05). Mean arterial pressures and results of oral
      glucose tolerance tests were similar during ALF, OLF, and second SHF; total
      cholesterol levels were also not significantly different. However, insulin
      sensitivity and HDL cholesterol diminished and LDL oxidizability increased with
      ALF. The marked rise in arterial compliance at least with alpha-linolenic acid
      reflected rapid functional improvement in the systemic arterial circulation
      despite a rise in LDL oxidizability. Dietary n-3 fatty acids in flax oil thus
      confer a novel approach to improving arterial function.

PMID- 9194771
TI  - Vitamin C reduces cholesterol-induced microcirculatory changes in rabbits.
AB  - The microcirculation was studied for 10 weeks in untreated rabbits (n = 12) and
      in rabbits treated with vitamin C in their drinking water (0.5 g/d; n = 6), a 1%
      cholesterol diet (n = 12), or a combination of the two treatments (n = 11). The
      studies were performed by direct intravital microscopic imaging of the
      conjunctiva of both eyes to evaluate blood flow velocity, microvessel diameter,
      and microhemorheologic conditions. As we reported previously, changes occurred in
      all of the aforementioned variables as a consequence of cholesterol feeding.
      After 3 and 6 weeks of feeding, there was a marked and significant (P < .0001)
      decrease in blood flow velocity in third-order arterioles, which was accompanied
      by stasis and erythrocyte aggregation in the smaller conjunctival vessels. When
      cholesterol treatment was combined with vitamin C, blood flow was almost
      identical to that of controls and significantly (P < .0001) higher than that of
      rabbits treated with cholesterol alone. All other changes were also significantly
      reduced by the addition of vitamin C treatment to the cholesterol diet.
      Cholesterol-treated rabbits developed macroscopic arterial lesions that were not
      significantly reduced by vitamin C treatment. Neither circulating oxysterol
      levels nor atheromas were reduced by vitamin C treatment, which also had no
      significant effect on lipid or circulating vitamin E levels. We have previously
      shown that the lipid-soluble antioxidant BHT is able to prevent both cholesterol
      induced microcirculatory changes and the development of arterial lesions in
      rabbits. This phenomenon is compatible with a critical oxidation step occurring
      in the lipid phase that is common to both processes. The finding that
      microcirculatory changes can be prevented by a water-soluble antioxidant is
      compatible with a role for water-soluble oxidants in this context. The
      possibility is discussed that vitamin C might also be important for the
      microcirculation in humans.

PMID- 9194770
TI  - Association of serum vitamin levels, LDL susceptibility to oxidation, and
      autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control
      study. The ARIC Study Investigators. Atherosclerosis Risk in Communities.
AB  - Oxidative modification of LDL is believed to be a crucial step in
      atherosclerosis. Thus, antioxidant vitamins may have a role in the prevention of
      coronary disease. We examined the cross-sectional association of serum vitamin
      levels, the susceptibility of LDL to hemin-induced oxidation (lag phase to
      conjugated diene formation), and the malondialdehyde-LDL (MDA-LDL) to native LDL
      radioactivity binding ratio with carotid intima-media thickness (IMT), a measure
      of asymptomatic early atherosclerosis. The participants in this observational
      study were 231 asymptomatic age-, sex-, race-, and field center-matched case
      control pairs selected from the Atherosclerosis Risk in Communities (ARIC) study
      cohort on the basis of B-mode carotid artery ultrasonograms obtained from 1986
      through 1989. Cases exceeded the 90th percentile of IMT, and control subjects
      were below the 75th percentile of IMT for all arterial segments. Biochemical
      analyses were performed on fasting frozen (-70 degrees C) serum specimens
      collected from 1990 through 1992. In conditional logistic regression adjusting
      for age, blood storage time, total cholesterol, and log-triglyceride
      concentrations, serum beta-cryptoxanthin and lutein plus zeaxanthin levels were
      inversely related to the extent of atherosclerosis (odds ratio [OR] per 1-SD
      increase: 0.75, 95% confidence interval [CI]: 0.59-0.94; and OR per 1-SD
      increase: 0.76, 95% CI: 0.59-0.95, respectively). Increases in alpha-carotene and
      lycopene were associated with nonsignificantly lower odds of being a case,
      whereas beta-carotene, retinol, and alpha-tocopherol were unrelated to IMT.
      Although not reaching statistical significance, the lag phase and autoantibodies
      against MDA-LDL were positively associated with asymptomatic atherosclerosis.
      After adjustment for potential confounders, only the inverse association of
      lutein plus zeaxanthin with asymptomatic atherosclerosis was maintained. This
      study supports a modest inverse association between circulating levels of some
      carotenoids, particularly lutein plus zeaxanthin, and carotid IMT. These findings
      suggest that these carotenoid compounds (regarded as biomarkers of fruit and
      vegetable intake) may be important in early stages of atherosclerosis.

PMID- 9194772
TI  - Importance of platelets in neutrophil adhesion and vasoconstriction after deep
      carotid arterial injury by angioplasty in pigs.
AB  - In previous studies we have shown that platelets can support neutrophil adhesion
      to the injured vessel wall in vitro and that neutrophils contribute to vascular
      tone regulation after arterial injury in vivo. In this study, we investigated the
      implication of platelets in neutrophil adhesion and the vasomotor response to
      arterial injury in vivo. 111In-labeled neutrophil adhesion and angiographic
      vasoconstriction were quantified after deep carotid arterial injury by balloon
      angioplasty in normal (n = 8), thrombocytopenic (n = 7), and aspirin-treated (2
      mg/kg IV, n = 7) pigs. Thrombocytopenia was produced by a polyclonal antiplatelet
      serum that depleted circulating platelet count by 84% without influencing
      neutrophil count. In the control animals, neutrophil adhesion (x 10(4)/cm2) at
      the site of deep arterial injury averaged 26.8 +/- 4.0 and decreased
      significantly to 11.5 +/- 2.3 and 11.2 +/- 2.4 in the thrombocytopenic and
      aspirin groups, respectively. The degree of vasconstriction was also reduced
      significantly, from 55.5 +/- 3.8% in the control group to 31.4 +/- 6.2% after
      platelet depletion and to 23.6 +/- 4.5% in the aspirin-treated group. Neutrophil
      adhesion to intact noninjured adjacent arterial segments was low in all groups
      and was not affected by the antiplatelet serum or by aspirin. In in vitro
      superfusion flow chambers, neutrophil adhesion to damaged arterial segments
      increased in the presence of platelets in a concentration-dependent manner and
      was not influenced by the antiplatelet serum. This study demonstrates that
      platelets can modulate neutrophil adhesion to the deeply injured arterial wall
      and that both elements may influence the degree of postangioplasty
      vasoconstriction in vivo.

PMID- 9194773
TI  - O.R. time--not beds.

PMID- 9194774
TI  - Sister Joseph's nodule.

PMID- 9194775
TI  - Radiology for the surgeon. Case 15. Presentation. Non-displaced intertrochanteric
      hip fracture (the occult hip fracture).

PMID- 9194776
TI  - Programmed cell death (apoptosis) and the resolution of systemic inflammation.

PMID- 9194777
TI  - Long-term survival after hepatic cryosurgery versus surgical resection for
      metastatic colorectal carcinoma: a critical review of the literature.
AB  - OBJECTIVE: To critically assess the evidence for long-term survival after hepatic
      resection and hepatic cryosurgery for metastatic colorectal cancer. The purpose
      of this review is to determine if a randomized controlled trial comparing these
      two treatment modalities is justified. DATA SOURCES: A review of the medical
      literature from 1973 to 1995 using the MEDLINE and CANCERLIT databases.
      References were also retrieved from the bibliographies of identified articles and
      from experts in the field of hepatobiliary and pancreatic surgery. STUDY
      SELECTION: One hundred and seventy-eight studies were reviewed. Studies
      presenting original data on the results of hepatic resection or cryotherapy for
      colorectal liver metastases were selected. Studies were excluded if they did not
      present survival data longer than 2 years. Studies pertaining to resection for
      fewer than 60 patients with colorectal metastases to the liver were excluded.
      DATA EXTRACTION: Data forms were designed before studies were examined in detail.
      All studies that met the inclusion and exclusion criteria were reviewed and the
      identified data extracted and tabulated. DATA SYNTHESIS: No controlled studies
      were identified, only case series. Four reports on hepatic cryosurgery and 9 on
      hepatic resection met the study criteria. The cryosurgery studies were
      methodologically poor; the resection studies were larger and more
      methodologically sound. The median follow-up for cryosurgery ranged from 12 to
      28.8 months, that for resection 21 to 69 months. There is clear evidence that
      hepatic cryosurgery has a role in the management of selected patients with
      colorectal metastases to the liver. However, valid conclusions cannot be made
      about the 5-year survival rate. The results of the studies on hepatic resection
      in patients with colorectal metastases to the liver have greater validity and
      consistency, with 5-year survival rates of 20% to 40%. CONCLUSIONS: Although
      hepatic cryosurgery offers some unequivocal and other potential advantages over
      surgical resection for colorectal metastases to the liver, the published data do
      not support its use in patients with resectable disease outside a clinical trial,
      and do not yet justify a randomized trial. A study that collects prospective data
      on 2 groups of patients (resectable v. unresectable) who differ only in the
      anatomic location of their metastases within the liver is needed.

PMID- 9194778
TI  - Symposium on the management of inguinal hernias. 1. Introduction.

PMID- 9194779
TI  - The repair of inguinal hernia: 110 years after Bassini.

PMID- 9194780
TI  - Laparoscopic groin hernia surgery: the TAPP procedure. Transabdominal
      preperitoneal hernia repair.
AB  - OBJECTIVE: To describe the technique and results of laparoscopic transabdominal
      preperitoneal (TAPP) hernia repair. DESIGN: A case series, with a detailed
      description of the operative technique. SETTING: A university affiliated
      hospital. PATIENTS: A consecutive series of 554 patients (494 male, 60 female)
      who underwent laparoscopic hernia repair in a single institution. The mean follow
      up was 14 months. INTERVENTIONS: Laparoscopic TAPP hernia repair was performed in
      almost all patients. Simple closure was performed in a patient with a
      strangulated hernia, and a mesh-based repair was used in a patient with bilateral
      obturator hernias. MAIN OUTCOME MEASURES: Complications and recurrence. RESULTS:
      The laparoscopic TAPP repair was successful in 550 of the 554 patients who
      underwent 632 hernia repairs. conversion was necessary in 4 patients.
      Complications were infrequent and there were no recurrences. Only 3.4% of
      patients were lost to follow-up. The most frequent complications were urinary
      retention (27) and hematoma and seroma (38) in the early postoperative period.
      Neuralgia (11) and hydrocele (10) also occurred. Mesh infection occurred in only
      1 patient and port-site hernias in 3 patients. there was 1 death from an acute
      myocardial infarction. CONCLUSION: Laparoscopic TAPP hernia repair is associated
      with an exceedingly low recurrence rate and an acceptable complication rate.

PMID- 9194781
TI  - The Shouldice technique: a canon in hernia repair.
AB  - Controversy exists on the merits of the various approaches to inguinal repair.
      Evolution of the classic open repair has culminated in the Shouldice repair.
      Challenges from newcomers, namely, tension-free repair and laparoscopy, are being
      examined. These two techniques have a number of disadvantages: the presence of
      foreign bodies (prostheses) and their implication in cases of infection; the cost
      of prosthetic material, which is no longer negligible (particularly with expanded
      polytetrafluoroethylene); and problems of safety in that the laparoscopic
      approach is no longer a dependable asset except in the hands of a highly
      specialized and dextrous operator. Still, complications occur with laparoscopic
      repair that should not be associated with a surgical procedure that is considered
      benign, safe and cost-effective. Surgeons must recognize the pertinent facts and
      decide according to their conscience which method of repair to use.

PMID- 9194782
TI  - Sutureless technique: second version.
AB  - Mesh repairs have revolutionized hernia surgery. When used to patch or plug a
      musculoaponeurotic abdominal wall defect, the results have been much better than
      traditional pure tissue repairs. The difference is simple: patch and plug
      techniques avoid tension on tissues. The improved sutureless repair not only
      avoids tissue tension, it obviates the need to suture the mesh. Fixation is
      achieved by intra-abdominal pressure, the same force that caused the hernia.
      Thorough dissection of the inguinal canal and the indirect sac is essential to
      avoid early failure. Whereas various repairs can be used with excellent results,
      there is no substitute for a complete dissection of the peritoneal sac well into
      the iliac fossa. The improved sutureless repair offers 2 advantages over the
      original version: (a) type III hernias can now be repaired without opening the
      canal's posterior wall, and (b) the incidence of clinically evident seroma has
      been reduced by 90%. Most primary and recurrent groin hernias can be repaired
      under local or regional anesthesia on an outpatient basis. Immediate ambulation
      and prompt recovery accompany this technique. Most patients resume full activity
      and employment by the end of the first week. The procedure is simple to learn,
      easy to perform and less costly than other techniques.

PMID- 9194783
TI  - Is wound infiltration with anesthetic effective as pre-emptive analgesia? A
      clinical trial in appendectomy patients.
AB  - OBJECTIVE: To assess the efficacy of wound infiltration with local anesthetic in
      reducing postoperative pain after a muscle-splitting incision for appendectomy.
      DESIGN: A double-blind, placebo-controlled, randomized clinical trial. SETTING:
      The Royal Columbian Hospital, a university-affiliated community hospital.
      PARTICIPANTS: Forty-three patients scheduled to undergo emergency appendectomy
      were randomized into treatment (21) and control (22) groups. Five patients were
      excluded from the treatment group. INTERVENTIONS: Local anesthetic infiltration
      of the wound before incision (treatment group) and saline infiltration (control
      group). MAIN OUTCOME MEASURES: Postoperative analgesic requirements, pain
      assessment by visual analogue scale and length of hospital stay. RESULTS: No
      significant difference in analgesic use was seen between the 2 groups, as
      measured at 3 stages (Mc = control mean [standard deviation], Mt = treatment mean
      [standard deviation]): (a) in the recovery room, intravenous morphine use was Mt
      = 6.6 mg [8.6] v. Mc = 10.1 mg [7.2]; (b) in the first 2 postoperative days,
      intramuscular meperidine use was Mt = 309 mg [181] v. Mc = 278 mg [125] on day 1
      and was Mt = 121 mg [132] v. Mc = 97 mg [128] on day 2; (c) in the final 5 days
      of follow-up, oral analgesic use was Mt = 11 [17] tablets v. Mc = 21 [16] tablets
      (acetaminophen with codeine). Pain assessments at rest, on a scale of 1 to 10,
      were found to be no different between groups, ratings being Mt = 4.7 [2.1] v. Mc
      = 4.5 [2.0] on day 1. Length of hospital stay averaged 3.0 days in both groups.
      CONCLUSIONS: Infiltration with local anesthetic before incision does not pre-empt
      postoperative pain from a muscle-splitting incision used for appendectomy.

PMID- 9194784
TI  - The management of spinal metastasis in children.
AB  - OBJECTIVE: To seek an optimal treatment plan from the results of treatment for
      metastatic disease of the spine in children. DESIGN: An 8-year retrospective
      study of children with metastatic disease of the spine. Imaging studies were
      reviewed and treatment modalities analysed. SETTING: The divisions of pediatric
      orthopedics and pediatric neurosurgery at the Children's Hospital of Eastern
      Ontario, Ottawa. PATIENTS: All children seen between April 1980 and December 1987
      who had lesions metastatic to the spine by hematogenous or direct extension.
      There were 20 children (15 boys, 5 girls) with a mean age at the time of
      diagnosis of 9.5 years. Follow-up ranged from 2 weeks to 108 months. One child
      was lost to follow-up. INTERVENTIONS: Eleven children underwent laminectomy and
      decompression. Of the 14 neurologically compromised children, 5 received
      chemotherapy and radiotherapy and 9 received chemotherapy, radiotherapy and
      surgery. MAIN OUTCOME MEASURES: Type of metastatic lesion, vertebrae involved and
      response to therapy. RESULTS: Vertebrae involved with metastases were as follows:
      cervical (3), thoracic (5), lumbar (8) and multilevel (2). Meninges were involved
      in 2 cases. The most common causes of metastatic spinal involvement were
      neuroblastoma (4 cases) and astrocytoma (6 cases). Pathologic fractures occurred
      in 4 children and kyphoscoliosis in 4. Spinal cord paresis developed in 14 of the
      20 children. Of the 6 children who survived from 48 to 108 months, 5 had tumours
      of neural origin, 4 being astrocytomas. Children with neuroblastoma or leukemic
      infiltration had a good initial response to chemotherapy. Five of the 6 surviving
      children had astrocytomas, and 5 were treated by surgical decompression.
      CONCLUSIONS: Metastatic disease of the spine in children secondary to astrocytoma
      should be treated aggressively, but from the experience gained from this study it
      is impossible to devise a rigid treatment plan for each type of metastatic
      tumour. The choice of chemotherapy, radiotherapy or surgery depends on the type
      of tumour, the age of the child and whether or not the spinal cord is
      compromised.

PMID- 9194785
TI  - Sporadic ampullary hamartoma simulating cancer.
AB  - Ampullary tumours are uncommon. They may occur with familial polyposis syndromes
      or neurofibromatosis. It can be difficult to distinguish them from their
      periampullary counterparts on clinical, radiologic or histologic grounds. Because
      most ampullary and periampullary tumours are malignant, they tend to be treated
      by radical surgery. A 67-year-old man was seen with a sporadic ampullary
      hamartoma that simulated cancer. It was successfully treated by local excision
      through a transverse duodenotomy.

PMID- 9194786
TI  - Preventing heat-related illness.

PMID- 9194787
TI  - Pruritic rash of the hands and feet.

PMID- 9194788
TI  - Alcohol abuse: medical effects of heavy drinking in late life.
AB  - As many as 15% of community-dwelling older persons are heavy drinkers, but their
      alcoholism is often hidden from their physicians. Depression, loneliness, and
      lack of social support are the most frequently cited antecedents to drinking for
      older alcoholics. Clinically, the same amount of alcohol once consumed with
      impunity may cause clinical symptoms in late life. Physiologic changes in volume
      of distribution make older patients susceptible to acute alcohol toxicity, with
      its CNS effects and metabolic disturbances. Liver disease, nutritional
      deficiencies, and impotence are consequences of chronic alcohol abuse.

PMID- 9194789
TI  - Giant cell arteritis and polymyalgia rheumatica: clues to early diagnosis.
AB  - Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related
      disorders found predominantly in older patients. These disorders, which are being
      recognized more frequently, are more common in women, in Caucasians, and in
      various geographic locations. Early recognition and treatment may prevent
      possible catastrophic consequences of GCA, such as blindness, stroke, or
      dissection of the aorta. Although diagnosis is fairly easy with the classic
      presentation, it may be missed when the patient presents with nonspecific
      constitutional symptoms. An increased awareness among primary care physicians
      will aid in the prevention of much of the morbidity and mortality related to
      these diseases.

PMID- 9194791
TI  - Breast health at midlife: guidelines for screening and patient evaluation.
AB  - Breast cancer is the leading cause of death of American women aged 40 to 55. The
      fear that midlife women have of developing breast cancer must be considered as
      physicians discuss breast health with their patients. Identification of risk
      factors is important, although 70% of women diagnosed with breast cancer have no
      known risk factors. Screening mammograms can detect early lesions, but
      controversy exists over whether they reduce mortality in women younger than ago
      50. The American Cancer Society and the National Cancer Institute recently
      changed their screening mammography recommendations for women aged 40 to 49. A
      breast self-exam can be performed using the circular or wedge techniques. If a
      mass is found, physicians can help alleviate a patient's anxiety by providing a
      diagnosis as quickly as possible.

PMID- 9194790
TI  - In-office screening for age-related hearing and vision loss.
AB  - Impairment in hearing and vision are common for persons age 65 and older, and
      severe impairments may result in dependencies in daily activities. Hearing loss
      with age often results in diminished ability to communicate with others and may
      lead to isolation, depression, and cognitive changes. A hearing evaluation
      involving simple screening tools in important for early recognition and treatment
      of otologic conditions. Cataracts, macular degeneration, diabetic retinopathy,
      and glaucoma are the most sight-threatening ocular diseases of aging. Visual loss
      usually occurs gradually and may go unrecognised for some time. Primary care
      screening is important to preserve sight and prevent disability and loss of
      function.

PMID- 9194792
TI  - Geriatrics photo quiz. Stokes-Adams attack.

PMID- 9194793
TI  - Osteoporosis: epidemic of the 21st century?

PMID- 9194794
TI  - Revisiting Vietnam.

PMID- 9194795
TI  - Case in point. Gout.

PMID- 9194796
TI  - Low voltage, Q waves, and congestive heart failure.

PMID- 9194798
TI  - Case in point. Perinephric abscess.

PMID- 9194797
TI  - A retired postal worker with back pain and leg weakness.
AB  - A 61-year-old former postal worker presented with progressive pain in his lower
      back, weakness in his right leg, and numbness in his left foot. In recent weeks,
      he had dragged his right leg in order to walk. He had also had intermittent
      diarrhea and dysuria but no hematuria or weight loss.

PMID- 9194799
TI  - Managed care from my perspective.

PMID- 9194800
TI  - Evaluation and treatment of acute knee pain.

PMID- 9194801
TI  - Population-based medicine for the primary care physician.

PMID- 9194802
TI  - Syncope in a man with a history of chest pain.

PMID- 9194803
TI  - Homocysteine, oxidative stress, and vascular disease.
AB  - First recognized in patients with rare inborn errors of metabolism, the
      association of elevated plasma homocysteine concentrations with atherosclerosis
      and thrombosis now seems relevant to the general population as well. The
      mechanism of injury appears to involve oxidative damage to endothelial cells.
      Vitamin supplementation can normalize homocysteine levels and may lower the
      incidence of atherothrombotic vascular disease.

PMID- 9194804
TI  - Hantaviruses: four years after four corners.
AB  - Hantavirus pulmonary syndrome is an acute, often fatal, febrile illness causing
      rapid pulmonary failure and cardiovascular instability. Since first described in
      1993, considerable progress has been made in identifying the hantaviruses
      responsible for the disease and in defining its epidemiologic and diagnostic
      features.

PMID- 9194805
TI  - Genotype and phenotype in cystic fibrosis.
AB  - Questions about the function of the disease-related gene are still not fully
      answered, but correlations are emerging between specific mutations and a
      patient's clinical condition. The strongest link is for pancreatic failure. A
      second involves azoospermia. Indeed, mutations are being found in males with
      infertility as the sole sign of disease. Improved knowledge of such patterns may
      suggest novel approaches to severe cystic fibrosis.

PMID- 9194806
TI  - Meeting the frustrations of chronic fatigue syndrome.
AB  - Patients face long-term disability, a variable prognosis, and too often,
      skeptical or misinformed doctors. Physicians lack laboratory markers or
      definitive treatment. Nevertheless, the diagnosis can be made with confidence by
      applying established diagnostic criteria- and selected laboratory studies to
      exclude other disorders-while symptomatic medication can provide support until
      recovery begins.

PMID- 9194807
TI  - When a child with a chronic condition needs hospitalization.
AB  - The hospitalization of a chronically ill child requires meticulous orchestration.
      Treatment recommendations must be transmitted to the family in a coherent and
      supportive fashion. Patient comfort and nutrition must be maintained, and
      psychological support provided. Discharge planning is often extensive. To promote
      continuity of care, appointment of a case manager is recommended.

PMID- 9194808
TI  - Chronic back pain after hernia and aneurysm repairs.

PMID- 9194809
TI  - Managing postmenopausal cystitis.
AB  - Cystitis caused by prolonged estrogen deprivation may be grossly underreported.
      This may be why many advocates of hormone replacement therapy focus on its
      cardiovascular and skeletal benefits while ignoring the bladder and urethra.

PMID- 9194810
TI  - Upper GI bleeding in a man with a left upper quadrant mass.

PMID- 9194811
TI  - In memoriam. Raymond Millard Cable 1909-1995.

PMID- 9194812
TI  - Ultrastructure of infective larvae (L3) of Onchocerca volvulus (Nematoda:
      Filarioidea) developed in Simulium yahense in Liberia.
AB  - Third-stage infective larvae of Onchocerca volvulus were examined to elucidate
      the ultrastructure and the interrelations of the stoma, esophagus, intestine, and
      nervous system. The alimentary canal involves a cuticularized stoma with a
      triradiate lumen that is continuous with a similar triradiate lumen in the
      muscular region of the esophagus. The lumen wall may be laterally appressed or
      opened into a stellate form in the glandular region. Posteriad from the
      esophagointestinal valve, the cylindroid lumen becomes partially occluded with
      microvilli formed by the evaginations of the apical membranes of the intestinal
      epithelium. Cross sections, through this region reveal that groups of 5 radiating
      epithelial cells are joined near the lumen surface by junctional complexes. The
      alimentary canal terminates via a rectal valve and channel supported by somatic
      and neural cells. The central nervous system consists of a nerve ring that
      surrounds the muscular region of the esophagus. Related neurons support
      chemoreceptors and tactoreceptors of sensilla and the extensive coelomyarian and
      meromyarian somatic muscles. Extensive accumulations of glycogen rosettes are
      present in many of the muscle and hypodermal cells.

PMID- 9194813
TI  - Autoradiographic analysis of the germinative tissue in evaginated Taenia solium
      metacestodes.
AB  - Evaginated Taenia solium metacestodes dissected from infected pork meat were
      incubated in vitro in RPMI 1640 medium with tritiated thymidine, washed, and
      further incubated for various chase periods. Worms were fixed and embedded in
      Poly/Bed and sections were processed for autoradiography. Results showed that all
      longitudinal sections had a germinative region located 500-700 mm posterior to
      the apex of the scolex with tegumentary cytons arranged in staggered columns
      perpendicular to the tegument. After 6-hr pulse and 0-12-hr chase periods, a
      large number of labeled cells were found in the parenchyma and tegumentary wall,
      included were myocytons, calcareous corpuscle cells, flame cells, osmoregulatory
      channel cells, and, in the medullary parenchyma, labeled undifferentiated round
      cells with a large nucleus, prominent nucleolus, abundant ribosomes, and no
      cytoplasmic organelles. These undifferentiated cells were not labeled after 24-hr
      and 48-hr chase periods, an observation that strongly suggests these cells divide
      and migrate toward the tegument in a pattern similar to that described for other
      cestodes. The morphology and localization of these cells support the view that
      they are stem cells that give rise to the various cell types of the tegumentary
      wall. The results indicate that T. solium contains a germinative tissue similar
      to that described in other cestodes, in which stem cells proliferate
      continuously, differentiate, and migrate to the tegument, constituting the main
      process by which these worms develop from metacestode to the adult stage.

PMID- 9194814
TI  - Caenorhabditis elegans cuticle: a description of new elements of the fibrous
      layer.
AB  - At the ultrastructural level, the Caenorhabdits elegans cuticle shows the
      presence of well defined layers; 1 of them is the fibrous layer composed by 2
      strands of fibers that meet each other at a 60 degrees angle and resembling a
      fish-bone pattern. In this paper, we describe new elements of the fibrous layer.
      When thin sections were obtained at a very low angle, i.e., almost tangential,
      fibers of wavy appearance could be observed. Those elements were 300 nm in length
      and 20 nm thick and were linked to each other by delicate dots. Deep-etched
      replicas of C. elegans revealed more details of the arrangement of new elements
      in the fibrous layer. The wavy fibers were organized in 5-sided, honeycomblike
      figures. Each pentagonal fiber was 145 nm across and was composed of tightly
      packed globular structures arranged linearly.

PMID- 9194815
TI  - Ectoparasite fauna of the eastern woodrat, Neotoma floridana: composition,
      origin, and comparison with ectoparasite faunas of western woodrat species.
AB  - We collected ectoparasites from eastern woodrats, Neotoma floridana, from 3 sites
      in the southeastern United States: coastal South Carolina, southeast Georgia, and
      south-central Georgia. Twelve ectoparasite species were recovered from 47
      woodrats in South Carolina (5 ticks, 5 mites, 2 fleas), 13 from 35 woodrats in
      south-central Georgia (1 tick, 10 mites, 2 fleas), and 4 from a small host sample
      (7) in southeast Georgia (2 ticks, 1 mite, 1 flea). New state records are
      established for the listrophorid mite Listrophorus neotomae from both Georgia and
      South Carolina, the myocoptid mite Myocoptes neotomae from Georgia, and the
      ceratophyllid flea Orchopeas sexdentatus pennsylvanicus from South Carolina.
      Different ectoparasites predominated on woodrats at each site with the tick
      Ixodes minor being the most commonly collected species in South Carolina, the
      American dog tick Dermacentor variabilis in southeast Georgia, and the chigger
      Euschoengastia peromysci in south-central Georgia. Most of the 17 species
      recovered are known to parasitize several species of mammals, especially rodents,
      and none of them are host specific to N. floridana. However, the fleas Epitedia
      cavernicola and Epitedia neotomae are host-specific ectoparasites of eastern
      woodrats in other parts of their range. Also, 1 species of tick, 2 mites, and 3
      fleas parasitize eastern woodrats in addition to western woodrats. A similar lack
      of host specificity is apparent for the few previously documented collections of
      ectoparasites from eastern woodrats, including 1 detailed survey in Indiana.
      Conversely, Neotoma spp. woodrats inhabiting western North America are
      parasitized by a plethora of host-specific ectoparasites including 2 tick
      species, 5 mites (other than chiggers), 20 chiggers, 2 sucking lice, and 42
      fleas. Recognizing that western biotas are typically more speciose than
      corresponding eastern biotas in North America, we further propose that because
      eastern woodrats are the most recent and eastern descendants of the ancestral
      Neotoma stock, (1) some ectoparasite species failed to accompany the eastern
      woodrat lineage in its eastward dispersals, and (2) there has been insufficient
      time for a diverse assemblage of ectoparasites to co-evolve with eastern
      woodrats.

PMID- 9194816
TI  - Genetic markers for the identification of two tick species, Amblyomma dissimile
      and Amblyomma rotundatum.
AB  - Genetic markers are described for 2 species of reptile and amphibian ticks,
      Amblyomma dissimile and Amblyomma rotundatum, by allozyme electrophoresis. Fixed
      allelic differences in 4 out of the 8 examined loci allowed the unequivocal
      separation of both of these species. A strong correlation was found between these
      genetic markers and the relative size of the spurs in coxae IV but not with the
      punctuation pattern of the scutum. Moreover, no overlap was found in the
      distribution of relative spur sizes between samples of both species. The percent
      polymorphic loci and the mean percent heterozygosity per locus for A. rotundatum
      was considerably lower than that for A. dissimile. Differences in the amount of
      genetic variability may be related to their modes of reproduction.

PMID- 9194817
TI  - Detection of Schistosoma mansoni in Biomphalaria using nested PCR.
AB  - A nested polymerase chain reaction (PCR) protocol was developed for detecting the
      presence of Schistosoma mansoni sporocysts in intermediate host snails of the
      genus Biomphalaria. To accomplish this, rDNA genes encoding the 18S rRNA of S.
      mansoni and Biomphalaria alexandrina from Egypt were sequenced, as were 18S
      encoding genes of the 13-16-R1 and Salvador strains of Biomphalaria glabrata.
      Based on a comparison of host and parasite sequences, a nested set of PCR primers
      was designed to allow specific amplification of portions of S. mansoni 18S rDNA.
      These primers allowed detection of as little as 10 fg of S. mansoni DNA diluted
      in 100 ng of snail DNA and did not allow amplification of snail 18S sequences.
      Using nested PCR, the presence of a single S. mansoni sporocyst within an adult
      snail could be detected at 1 day postexposure. In DNA samples extracted from each
      of 74 snails of the M-line strain of B. glabrata exposed to from 1 to 10 S.
      mansoni miracidia for intervals ranging from 1 to 44 days, use of the outside
      primer pair alone detected the parasite's presence in 51% of the snails, whereas
      the sequential use of outside and nested primer pairs detected parasites in 92%
      of the snails. This approach has utility in determining if snails in endemic
      areas bear prepatent or inactive infections and in assessing the degree of
      compatibility between local snail and schistosome populations. It will also
      facilitate studies of resistance of snails to infection.

PMID- 9194818
TI  - PCR amplification of the mitochondrial DNA minisatellite region to detect
      Schistosoma mansoni infection in Biomphalaria glabrata snails.
AB  - Schistosoma infection in Biomphalaria glabrata can be detected by either exposing
      snails to light to induce cercarial shedding or by squeezing them between glass
      slides to detect parasites in the digestive gland and other regions. The methods
      available are inefficient for identification of prepatent infections and do not
      allow the diagnosis of infection in snails that die before arriving in the
      laboratory. Furthermore, infection is undetectable after migration of sporocysts
      from the head-foot region of the snail. We examined the use of polymerase chain
      reaction (PCR) amplification of minisatellite repeats from Schistosoma mansoni
      mitochondrial DNA (mtDNA) to identify snail infection. We found that
      amplification of mtDNA under low stringency conditions (LS-PCR) allowed for the
      identification of specific S. mansoni infection in Biomphalaria snails. To
      confirm these results, specific amplification reactions were performed using 2
      sets of primers that allowed for the diagnosis of infection and an internal
      control of the reaction (multiplex PCR). Results obtained using multiplex PCR
      demonstrated the ability of the assay to detect S. mansoni-specific infection.
      Thus, LS-PCR as well as specific multiplex PCR allow for the detection of
      prepatent infections and show high specificity for S. mansoni in comparison with
      other trematode infections in either living or dead snails.

PMID- 9194819
TI  - Genetic and ecological data on the Anisakis simplex complex, with evidence for a
      new species (Nematoda, Ascaridoidea, Anisakidae).
AB  - Isozyme analysis at 24 loci was carried out on anisakid nematodes of the Anisakis
      simplex complex, recovered from various intermediate/paratenic (squid, fish) and
      definitive (marine mammals) hosts from various parts of the world. A number of
      samples were found to belong to A. simplex sensu stricto and Anisakis pegreffii,
      widely extending the geographic ranges and the number of hosts of these 2
      species. In addition, a new distinct gene pool was detected, showing different
      alleles with respect to A. simplex s. str and A. pegreffii at 5 diagnostic loci
      (99% level). Samples with this gene pool were assigned to a new species,
      provisionally labeled A. simplex C. Reproductive isolation between A. simplex C
      and the other 2 Anisakis species was directly assessed by the lack of hybrid and
      recombinant genotypes in mixed samples from sympatric areas, i.e., Pacific Canada
      for A. simplex C+A. simplex s. str., South Africa and New Zealand for A. simplex
      C+A. pegreffii, even when such samples were recovered from the same individual
      host. Similar levels of genetic divergence were observed among the three species
      (DNei from 0.36 to 0.45). At the intraspecific level, Canadian Pacific and
      Austral populations of A. simplex C were found to be genetically rather
      differentiated from one another (average DNei = 0.08), contrasting with the
      remarkable genetic homogeneity detected within both A. simplex s. str. and A.
      pegreffii (average DNei about 0.01). Accordingly, a lower amount of gene flow was
      estimated within A. simplex C (Nm = 1.6) than within the other 2 species (Nm =
      5.4 and 17.7, respectively). Anisakis simplex C showed the highest average values
      of genetic variability with respect to both A. simplex s. str. and A. pegreffii,
      e.g., expected mean heterozygosity. Hr = 0.23, 0.16, and 0.11, respectively, in
      the 3 species. Data on geographic distribution and hosts of the 3 members so far
      detected in the A. simplex complex are given. Their ecological niche is markedly
      differentiated, with a low proportion of hosts shared. Intermediate and
      definitive hosts of A. simplex s. str. and A. pegreffii appear to belong to
      distinct food webs, benthodemersal, and pelagic, respectively; this would lead to
      different transmission pathways for the parasites.

PMID- 9194820
TI  - Phylogenetic analysis of Perkinsus based on actin gene sequences.
AB  - Perkinsus species presently are classified within the phylum Apicomplexa. This
      placement, however, is controversial. Based upon morphological observations and
      phylogenetic analyses of the small subunit ribosomal RNA gene, it has been
      suggested that Perkinsus may be more closely related to dinoflagellates. To
      reevaluate the phylogenetic position of Perkinsus, we obtained nucleotide
      sequence data for actin genes from Perkinsus marinus and 2 dinoflagellates,
      Prorocentrum minimum and Amphidinium carterae. Results indicated that there are 2
      closely related actin genes in the genome of P. marinus. Phylogenetic comparisons
      of these actin gene fragments of P. marinus to available actin gene sequences for
      several ciliates and apicomplexans and to the 2 actin gene sequences from
      dinoflagellates obtained in this study supported a closer affinity of P. marinus
      to dinoflagellates than to apicomplexans.

PMID- 9194821
TI  - Schistosoma mansoni: the immune response against cercarial glycocalyx.
AB  - Schistosoma mansoni cercarial glycocalyx was separated and purified by Sephacryl
      300 SR. It was found to stimulate the humoral immune response in mice injected
      with it. Antiglycoalyx antibodies raised in CD/1 mice were found to be cytotoxic
      to schistosomula in vitro. But conversely, no protective effect was demonstrated
      in vivo. Eosinophil-mediated cytotoxicity was found to have no effector function
      in the murine immune response against schistosomes. A monoclonal antiglycocalyx
      IgM was prepared during our study. It was found to have no cytotoxic effect on
      schistosomules in vitro. However, it was found to have an inhibitory activity
      blocking the cytotoxic effect of other antiglycocalyx isotypes in the immune
      mouse. The contradiction between the result of antiglycocalyx antibody-mediated
      cytotoxicity obtained in vivo and that obtained in vitro is in itself revealing
      and suggests that the effect is crucially dependent upon factors as yet poorly
      understood.

PMID- 9194822
TI  - Exposure of swine to Trichinella spiralis antigen as determined by consecutive
      ELISAs and western blot.
AB  - Exposure of swine to Trichinella spiralis was evaluated using a combination of 3
      consecutive enzyme-linked immunosorbent assays (ELISAs) based on larval T.
      spiralis excretory-secretory antigen as screening test and western blot analysis
      as confirmatory test. Ninety-three of 32,693 domestic swine sera collected in
      Georgia over a 5-yr period contained antibodies specific to T. spiralis
      (prevalence of exposure = 0.28%). The highest prevalence (0.52%) of exposure to
      T. spiralis was in samples from stockyards and salebarns. Prevalence of exposure
      in samples from cull sows from 1 slaughter house was 0.38% compared with 0.17% in
      samples obtained from farms. Pepsin-HCl digestion of diaphragms from 49 swine
      from 6 seropositive farms revealed 0.01 larvae/g in 4 swine from 3 farms.
      Determination of T. spiralis infection status of farms appears to be accurately
      determined with this combination of exploratory ELISAs and confirmatory western
      blot analysis.

PMID- 9194823
TI  - Temperature modulation of the response of Ig-positive cells to Goussia carpelli
      (Protozoa: Apicomplexa) infections in carp, Cyprinus Carpio L.
AB  - The influence of temperature on the kinetics of immunoglobulin-positive (Ig+)
      leukocytes in cell suspensions prepared from the pronephros and the intestine of
      common carp Cyprinus carpio during the development of Goussia carpelli, a gut
      dwelling coccidian parasite, was examined. The development of the parasite was
      temperature dependent. At 20 C, oocysts were formed 2-3 wk postexposure (PB), at
      15 C for 3-4 wk PE, and at 12 C for 5-6 wk PE. At all 3 temperatures, changes of
      relative numbers of Ig+ cells were observed in cell suspensions. During merogony
      and gamogony, the proportion of Ig+ cells increased, peaked during oocyst
      formation of the parasite, and then remained elevated. Serum collected from
      infected carp 8-20 days PE contained immunoglobulins binding to G. carpelli
      merozoites. The development of the parasite and the increase of Ig+ cells in
      intestine and pronephros of infected carp were temperature dependent. The peak
      level of Ig+ cells appeared not to be influenced by temperature. These findings
      indicate that even at low temperatures local and systemic immune responses are
      induced in carp with enteritic parasite infection.

PMID- 9194824
TI  - Immunohistochemical diagnosis of Toxoplasma gondii: potential for cross
      reactivity with Neospora caninum.
AB  - A monoclonal antibody (MAB 3F5) was compared with a commercial polyclonal
      antibody for specificity for Toxoplasma gondii and cross-reactivity with Neospora
      caninum in paraffin-embedded tissue sections. Both antibody preparations reliably
      recognized T. gondii tachyzoites (RH isolate) in animal tissues but did not
      always label tissue cysts (ME-49 isolate). The commercial antibody strongly cross
      reacted with N. caninum tachyzoites, but MAB 3F5 did not when the
      immunoperoxidase, immunofluorescence, or immunogold procedures were employed, nor
      did it cross-react with other apicomplexans, e.g., Isospora suis, Eimeria bovis.
      Sarcocystis cruzi, Hammondia hammondi, or Caryospora bigenetica. Immumoelectron
      microscopy revealed that MAB 3F5 bound to dense granules in extracellular T.
      gondii tachyzoites. In western blots of T. gondii tachyzoites, a major band at 38
      kDa and a minor band at 32 kDa were labeled by MAB 3F5, but no labeling of the
      proteins of N. caninum tachyzoites or uninfected host cells occurred at the
      ultrastructural level or in immunoblots.

PMID- 9194825
TI  - Migration and development of mother sporocysts of Echinostoma caproni (Digenea:
      Echinostomatidae).
AB  - Experimental infections of the mollusc Biomphalaria pfeifferi by Echinostoma
      caproni miracidia (Mi) were carried out in order to analyze the migration and
      development of mother sporocysts (MS) at 26 C. Miracidia penetrated different
      parts of the host's body, such as the mantle collar, the foot and head covering
      (including velum and tentacles), the mantle cavity, and the oral cavity. The
      ventricle and common aorta were the final sites of infection for the mother
      sporocysts after migration. The path of migration of the sporocyst was influenced
      by the point of MS penetration, but in all cases the MS reached the ventricle
      through the venous system. Developmental studies showed that newly hatched Mi
      contained 5-7 germinal cells (the primary germinal cells) and some
      undifferentiated cells. During sporocyst development, every primary germinal cell
      apparently gave rise to a redial embryo, whereas undifferentiated cells gave rise
      to both somatic and secondary generative cells. The eventual degeneration of the
      sporocyst seemed to cause the end of the development of this germinal material.
      The MS produced about 15 mother rediae (MR). Intramolluscan development of E.
      caproni MS consisted of 5 main periods: (1) resting, (2) migration, (3) growth,
      (4) reproduction, and (5) degeneration. A lower temperature of 21 C affected the
      duration of each stage. However, the path of sporocyst migration, the pattern of
      their growth, and the developmental steps of the germinal material were similar.

PMID- 9194826
TI  - Experimental Schistosoma bovis infection in goats: the inflammatory response in
      the small intestine and liver in various phases of infection and reinfection.
AB  - In a histopathological study of goats experimentally infected with Schistosoma
      bovis, the characteristics of the inflammatory response in the small intestine
      and liver related to tissue egg counts and fecal egg excretion were compared
      between goats at different time periods of primary infection and of primary
      infection followed by challenge. At early patency, coinciding with increasing egg
      excretion, the intestinal lamina propria showed numerous intact schistosome eggs
      devoid of any inflammatory reaction, whereas egg-associated inflammatory foci in
      the intestine were significantly few. Later in primary infection and after
      challenge, intestinal changes were marked by a granulomatous anti-egg response,
      with only a minor component of eggs lacking inflammatory change, and were
      consistent with a reduction of egg transfer into the gut wall. Hepatocellular
      necrosis with eosinophil infiltration was pronounced only during the early patent
      stage. The results indicate that the early cascade of fecal egg excretion in
      caprine schistosomosis bovis is aided by a low degree of tissue reactivity to
      eggs in the intestine. They also lend support to previous findings indicating
      that an anti-fecundity effect is operative after exposure to challenge in this
      parasitic infection in goats.

PMID- 9194827
TI  - Accelerated inflammatory bowel disease of TCR-alpha-deficient mice persistently
      infected with Cryptosporidium parvum.
AB  - TCR-alpha-deficient mice spontaneously develop inflammatory bowel disease (IBD)
      at 8-9 mo old. This study characterizes an accelerated form of IBD induced by
      Cryptosporidium parvum infection. Cryptosporidium parvum-infected TCR-alpha
      deficient mice developed IBD as early as 4 wk old when challenged at 1 wk old.
      The lesions of this accelerated IBD resembled the lesions of spontaneous IBD in
      TCR-alpha-deficient mice and consisted of a mononuclear cell infiltrate within
      the intestinal lamina propria and an increased proliferation of enterocytes. The
      mononuclear cells within the lamina propria consisted of B cells and gamma delta
      T cells. The distal ileum, cecum, and colon were grossly thickened due to a
      hyperplastic mucosa and edematous submucosa. The mechanism by which C. parvum
      infection accelerates development of IBD is presently unclear.

PMID- 9194828
TI  - Isospora tiaris n.sp. (Apicomplexa: Eimeriidae) from the sooty grassquit (Tiaris
      fuliginosa), a passeriform bird of South America.
AB  - Isospora tiaris n. sp. is described from the feces of an adult bird, a sooty
      grassquit (Tiaris fuliginosa) from Venezuela. The oocysts are subspherical, 27.1
      x 23.8 (24.7-30.0 x 21.2-26.5) microns with a bilayered, smooth, colorless wall.
      A micropyle and oocyst residuum are absent; an ellipsoidal polar granule is
      usually present. Sporocysts are ovoidal, 14.7 x 10.8 (12.4-16.8 x 8.8-12.4)
      microns with prominent Stieda and substieda bodies and a residuum composed of
      small uniform granules.

PMID- 9194829
TI  - Eimeria (Protozoa: Eimeriidae) from North American sciurids, Glaucomys sabrinus
      and Tamias townsendii: with a description of a new species.
AB  - From 1990 to 1991, 11 northern flying squirrels, Glaucomys sabrinus, and 30
      Townsend's chipmunks, Tamias townsendii, were live-trapped, marked, and released
      in MacDonald Forest, Benton Co., Oregon and their feces at each capture examined
      for the presence of coccidian parasites. Two eimerians were found in G. sabrinus:
      Eimeria dorneyi and a second species we describe here as new. One species,
      Eimeria vilasi, was identified from T. townsendii. Sporulated oocysts of the new
      eimerian are strongly ellipsoidal, pointed at 1 end, and are 47.2 x 25.0 (41-52 x
      22-31) microns with ovoidal sporocysts, 19.0 x 10.5 (17-21 x 9-11) microns. A
      micropyle and oocyst residuum are absent, but, occasionally, a polar granule is
      present in the oocyst. In the sporocysts, Stieda and substieda bodies are
      present, as is a membrane-bound residuum. Sporulated oocysts of E. dorneyi are
      uniformly ellipsoidal, 23.0 x 14.7 (17-26 x 13-16) microns with elongate
      ellipsoidal sporocysts, 11.6 x 5.7 (9-13 x 5-7) microns. A micropyle and oocyst
      residuum are absent, but 1 polar granule is present. A Stieda body is present,
      but sub- and parastieda bodies are absent. The sporocyst residuum is composed of
      granules in a compact mass. Here we provide phototype (hapantotype) specimens
      archived in a nationally accredited museum and a line drawing (cartoon) to
      supplement the one provided by Soon and Dorney because their drawing did not show
      the sporocyst residuum given in the written description.

PMID- 9194830
TI  - Sarcocystis buffalonis n.sp. (Protozoa: Sarcocystidae) from the water buffalo
      (Bubalus bubalis) in Vietnam.
AB  - Sarcocystis buffalonis n. sp. is proposed for a species forming thick-walled,
      macroscopic sarcocysts in skeletal muscles and the esophagus of the water buffalo
      (Bubalus bubalis). Sarcocysts of S. buffalonis were found in 68 (10.5%) of 647
      buffalo carcasses examined grossly at slaughter in Ho Chi Minh City in southern
      Vietnam. Sarcocystis buffalonis sarcocysts were 1-8 mm long and 0.1-0.5 mm wide.
      The cyst wall was 3-7.7 microns thick and had palisadelike villar protrusions
      that were constricted at the base, expanded laterally in the mid-region, and
      tapered distally. The villar protrusions contained microfilaments and electron
      dense granules. Sarcocysts of Sarcocystis fusiformis, the other well-known
      macroscopic species occurring in water buffalo, were also found in 60 of the 68
      animals infected with S. buffalonis. Sarcocysts of S. fusiformis were thin walled
      and had characteristic cauliflowerlike villar protrusions. Two of 7 cats fed
      isolated S. buffalonis sarcocysts were found to have 12 x 8 microns sporocysts in
      their intestine or feces 10 days after inoculation.

PMID- 9194831
TI  - Six species of Acanthobothrium (Eucestoda: Tetraphyllidea) in stingrays
      (Chondrichthyes: Rajiformes: Myliobatoidei) from Ecuador.
AB  - Six species of Acanthobothrium, 4 described as new, are reported in stingrays
      from southern Ecuador. Acanthobothrium atahualpai n. sp. in Gymnura afuerae most
      closely resembles Acanthobothrium fogeli and Acanthobothrium parviuncinatum by
      having bothridial hooks with recurved prongs and short handles. It differs from
      A. fogeli by having bothridial hooks 163-195 microns vs. 78-114 microns long and
      averaging 25 vs. 32 testes per pruglottis: it differs from A. parviuncinatum by
      having bothridial hooks 163-195 microns vs. 87 microns long and averaging 25 vs.
      13 testes per proglottis. Acanthobothrium minusculus n. sp. in Urolophus
      tumbesensis most resembles Acanthobothrium campbelli and Acanthobothrium vargasi
      by being no more than 3 mm long and having 6-30 testes per proglottis. It can be
      distinguished from them by having bothridial hooks averaging 86 microns vs. 108
      111 microns and 130-133 microns long, and 6-10 vs. 15-23 and 22-29 testes per
      proglottis, respectively. Acanthobothrium monksi n. sp. in Aetobatus narinari
      resembles Acanthobothrium tasajerasi from Himantura schmardae by having a
      prominent genital atrium and a large globose cirrus sac; it differs by averaging
      21 vs. 35 testes per proglottis and having bothridial hooks averaging 150 microns
      vs. 165 microns long. Acanthobothrium obuncus n. sp. in Dasyatis longus resembles
      a group of species characterized by wider than long to square immature and mature
      proglottides, bothridia at least partially fused to the scolex at their posterior
      ends, and asymmetrical ovarian arms with aporal arms extending anteriorly to the
      vaginal level. It resembles Acanthobothrium americanum by averaging 73 vs. 72
      testes per proglottis, but differs by having bothridial hooks averaging 120-131
      microns vs. 151 microns long; it resembles Acanthobothrium chilensis by having
      bothridial hooks averaging 120-131 microns vs. 130 microns long, but differs by
      averaging 73 vs. 90 testes per proglottis. Acanthobothrium campbelli in Urotrygon
      chilensis and Acanthobothrium costarricense in Dasyatis longus, previously known
      in those hosts from the Pacific coast of Costa Rica, are reported from Ecuador
      for the first time.

PMID- 9194832
TI  - Koronacantha pectinaria n. comb. (Acanthocephala: Illiosentidae) from
      Microlepidotus brevipinnis (Haemulidae) and redescription of Tegorhynchus brevis.
AB  - Tegorhynchus pectinarius Van Cleave, 1940, is redescribed on the basis of male
      and female specimens in Microlepidotus brevipinnis from the marine waters of
      Costa Rica and Mexico. The elongate proboscis with a heavy cuticular coating,
      cuticular body spines, 8 cement glands, and the heavy, strongly recurved hooks in
      the shape of an inverted apostrophe with roots that are simple but exaggerated in
      size with a small hook blade indicate that T. pectinarius should be assigned to
      Koronacantha Monks and Perez-Ponce de Leon, 1996. Koronacantha pectinaria n.
      comb. can be distinguished from Koronacantha mexicana in having strongly recurved
      hooks only on the dorsal side of the proboscis, a conspicuous patch devoid of
      normally developed hooks located just anterior to the recurved hooks, trunk
      spines extending from the anterior end of the trunk posteriorly over 85% of the
      trunk, lacking genital spines in both sexes, and by the basal comblike group of
      small close-set hooks made up of 5 to 7 hooks. In K. mexicana, the recurved hooks
      occur as a complete ring, no patchlike area devoid of hooks exists, trunk spines
      begin at posterior end of receptacle and extend posteriorly over rest of trunk,
      genital spines are present in both sexes, and the basal comblike group of small
      close-set hooks consists of 4 or 5 hooks. Tegorhynchus brevis Van Cleave, 1921,
      is redescribed based on the original specimens, and Tegorhynchus, Koronacantha,
      and Illiosentis are considered diagnostically distinct.

PMID- 9194833
TI  - Eimeria from bats of the world: two new species from Myotis spp. (Chiroptera:
      Vespertilionidae).
AB  - Between 1986 and 1995, 548 fecal samples were collected from 41 species of bats
      (Molossidae, Mormoopidae, Phyllostomidae, Thyropteridae, and Vespertilionidae)
      from New Mexico, California, Baja California Sur (Mexico), and Bolivia. Of these,
      the feces of 28 (5%) bats, including Antrozous pallidus, Myotis ciliolabrum,
      Myotis lucifugus, and Myotis yumanensis (Vespertilionidae), contained oocysts
      representing at least 3 species of Eimeria. A new species of eimerian from M.
      lucifugus (3/27, 11%) and M. yumanensis (8/70, 11%) is described. Sporulated
      oocysts are ellipsoidal, 22.3 x 14.8 (18-25 x 13-16) microns with micropyle
      (approximately 2 microns) and polar granules (1-4), but an oocyst residuum is
      absent. The oocyst wall is slightly rough exteriorly and has 2 layers (total < or
      = 1 micron thick). Football-shaped sporocysts are 8.1 x 6.6 (8-11 x 5-7) microns,
      each with a Stieda body and granular sporocyst residuum present. A new eimerian
      from M. yumanensis (4/70, 6%) and M. ciliolabrum (1/12, 8%) also is described.
      Sporulated oocysts are spheroidal to subspheroidal, 15.0 x 14.1 (14-16 x 14-16)
      microns, with micropyle and oocyst residuum absent; a polar granule is present.
      The wall is smooth and has 2 layers (total < 1 micron thick). Sporocysts are
      football-shaped, 7.1 x 5.9 (6-9 x 5-7) microns, each with a Stieda body and
      sporocyst residuum. The sporulated oocysts of a third morphotype, found in A.
      pallidus (12/85, 14%), were indistinguishable from those of Eimeria arizonensis,
      a species typically found in murid rodents. The currently recognized species of
      bat Eimeria are listed, and a dichotomous key is provided.

PMID- 9194834
TI  - Gregarina triboliorum (Eugregarinida: Gregarinidae) n. sp. from Tribolium
      confusum and resolution of the confused taxonomic history of Gregarina minuta
      Ishii, 1914.
AB  - The septate gregarine parasites of flour beetles (Tribolium spp.) include
      Gregarina minuta Ishii, 1914, a relatively small species in which both primite
      and satellite possess an obvious protomerite, and a larger species that lacks the
      satellite protomerite. The latter species has been placed in the genera
      Didymophyes and Hirmocystis by various authors, but studies reported here
      demonstrate that this species, herein described as Gregarina triboliorum,
      exhibits early pairing and produces oocyst chains, both characteristics of the
      genus Gregarina. The oocysts of this new species are described for the first
      time. In addition, experimental infections using oocyst from single gametocysts
      reveal that oocyst chain number is variable but is typically 1, 2, or 4. Prior
      experiments involving a related beetle, Tenebrio molitor, demonstrated extreme
      host specificity within the 4 Gregarina species parasitizing larval and adult
      hosts. However, G. triboliorum is not limited either stadially or specially,
      infecting both adults and larvae of Tribolium confusum and Tribolium castaneum.

PMID- 9194835
TI  - Detection of Neospora sp. from infected bovine tissues by PCR and probe
      hybridization.
AB  - Neospora sp. can cause fetal abortion or neurological disease in congenitally
      infected calves. Latent tissue stages in infected cows may contribute to vertical
      transmission of Neospora sp. from dam to offspring in multiple pregnancies. In
      this investigation, the polymerase chain reaction (PCR) and Neospora-specific
      assay were employed to detect Neospora sp. by amplification of nuclear small
      subunit rRNA gene sequences in infected cattle tissues. Tissues from 11 cattle,
      including 6 experimentally and 2 naturally infected cows, 1 naturally infected
      newborn calf, and 2 uninfected control cows, were evaluated in this study.
      Neospora-specific PCR products were amplified from DNAs of different bovine
      tissues, including brain, spinal cord, heart, lung, kidney, diaphragm, skeletal
      muscle, and placenta, as well as amniotic fluid samples of infected cattle. The
      PCR-based amplification and probe hybridization system proved useful in assessing
      the location of tissue-stage parasites in naturally and experimentally infected
      cattle, even when Neospora sp. antibody titers fall below normal cut-off values
      by an indirect immunofluorescent antibody test.

PMID- 9194836
TI  - Direct comparison of antimalarial activity among PS-15 combination therapies by
      bioassay of serum samples from treated Saimiri sciureus.
AB  - Sixteen Saimiri sciureus monkeys were administered PS-15-atovaquone, PS-15
      sulfamethoxazole, PS-15-dapsone, PS-15 alone, and atovaquone alone. The in vitro
      antimalarial activity of serum against Plasmodium falciparum obtained from these
      monkeys at 3, 6, and 12 hr after the administration of drug(s) were measured by
      bioassay and analyzed by Duncan's and Newman-Keul's tests. PS-15-atovaquone was
      found to be the most effective antimalarial combination, followed by PS-15
      sulfamethoxazole, PS-15-dapsone, PS-15 alone, and atovaquone alone. These dual PS
      15 combinations are effective combinations and, in-particular, PS-15-atovaquone
      is worthy of further evaluation.

PMID- 9194837
TI  - Relationship between Chagas' disease immunoreactivity in pericardial fluid and
      survival of children.
AB  - Pericardial fluid (PF) obtained at autopsy has been used for the study of fluid
      pericardium proteins in noninfectious and infectious diseases such as Chagas'
      disease. The aim of the present study was to determine the immunoreactivity to
      Chagas' disease in PF obtained at autopsy from children in an endemic area. A
      total of 251 autopsy records were surveyed from the files of the Medical School
      of Uberaba, Brazil, of children ranging in age from stillborn to 14 yr who had
      died between 1968 and 1992. The reactions for Chagas' disease
      (immunofluorescence, complement fixation, and hemagglutination) applied to PF
      were recorded. Thirty-four children (13.5%) showed positive reactions to Chagas'
      disease. The frequency of immunoreactivity was significantly related to age-group
      distribution (chi 2 = 13.4; P < 0.005). Children with negative PF tests who had
      died between 1 and 60 days of age presented a median survival time of 13 days;
      positive children presented a median survival time of 4 days (Z = 2.1; P = 0.02).
      These data indicate that the prevalence of Chagas' disease is high among pregnant
      women in southern Brazil. In addition, they also suggest that "antitrypanosome
      antibodies" detected in PF may be 1 of the indicators of age of infant death and
      may possibly play a role in the course of the disease in children born from
      mothers with Chagas' disease.

PMID- 9194838
TI  - Chronic infection with Toxoplasma gondii does not prevent acute disease or
      colonization of the brain with tissue cysts following reinfection with different
      strains of the parasite.
AB  - Two strains of Toxoplasma gondii with different capacities to induce disease and
      brain lesions in mice were used to study the effects of reinfection with the
      parasite on a previously infected host. In spite of marked antibody and cell
      mediated immune responses, chronically infected mice developed disease and died
      of acute toxoplasmosis when reinfected with a strain different from the one
      causing the primary infection. Moreover, the marked antibody and cell-mediated
      immune responses of the chronically infected mice did not prevent invasion of
      their brains and formation of tissue cysts by the reinfecting strain. Tissue
      cysts of the reinfecting strain were demonstrated in the brains of the
      chronically infected and subsequently reinfected mice. These results highlight
      the importance of strain differences in the pathogenesis of toxoplasmosis.

PMID- 9194839
TI  - Fatal hepatic sarcocystosis in two polar bears (Ursus maritimus).
AB  - Fatal hepatic sarcocystosis was diagnosed in 2 polar bears from a zoo in
      Anchorage, Alaska. Gross lesions were icterus and systemic petechiae. Marked
      microscopic lesions were detected only in the liver and included severe random
      necrotizing hepatitis with hemorrhage. Only asexual stages of an apicomplexan
      parasite were detected within hepatocytes, and rare extracellular zoites were
      seen in foci of necrosis. The parasite divided by endopolygeny, and occasionally
      merozoites formed rosettes around a central residual body. Ultrastructural
      features of the merozoites included a conoid and low numbers of micronemes at the
      apical pole, centrally located nuclei, and absence of rhoptries. The parasites
      failed to react with anti-Neospora sp., anti-Toxoplasma gondii, or anti
      Sarcocystis neurona sera. The microscopic and ultrastructural morphology of the
      parasite are most compatible with an apicomplexan protozoan of the genus
      Sarcocystis. The life cycle of this parasite in bears is not known.

PMID- 9194840
TI  - Sheep and goat lines of Teladorsagia circumcincta (Nematoda): from allozyme to
      morphological identification.
AB  - Previous allozyme analyses demonstrated the existence of Teladorsagia
      circumcincta sheep and goat lines, based on the presence (goat line) or absence
      (sheep line) of an allele at the cathodic loci of malate dehydrogenase (MDH),
      with rapid migration (coded sR or super rapid) when starch gel electrophoresis
      was used. Simultaneous allozyme and morphometric characterization of individual
      worms from 3 natural populations harbored by goats were assessed. The nematodes
      with sR allele could be identified by a combination of measures of the dorsal ray
      of the bursa. Simple and fast morphological differentiation of worms with sR
      allele constitute an attractive tool for thorough studies on the frequency of
      these 2 types of worms and finally to assess the prevalence of goat and sheep
      lines.

PMID- 9194841
TI  - Helminths of Anolis acutus (Sauria: Polychrotidae) from St. Croix, U.S. Virgin
      Islands.
AB  - Four hundred and fifteen Anolis acutus from St. Croix, U.S. Virgin Islands were
      examined for helminths. Three nematodes, Ascarops sp. (larvae), Parapharyngodon
      cubensis, and Spauligodon caymanensis, and 2 acanthocephalans, Centrorhynchus sp.
      and Oligacanthorhynchus sp. (cystacanths), were found. The highest prevalence
      (47%) and mean intensity (21.3) were recorded for S. caymanensis. Anolis acutus
      is a new host record for each of these helminth species.

PMID- 9194842
TI  - The results of anthelmintic-abbreviated infections of Trichostrongylus
      colubriformis and Teladorsagia circumcincta on fecal egg counts in goats on
      pasture.
AB  - Twenty, 2-yr-old angora goats kept on nematode larvae-contaminated pasture since
      birth were divided into 2 equal groups. Goats from group 1 were immunized by drug
      abbreviated infection, a procedure that gave high protection against field
      challenge in 12-moold sheep. Group 1 was orally dosed 3 times with increasing
      numbers of Trichostrongylus colubriformis and Teladorsagia circumcincta infective
      larvae. Each time, the infection was abbreviated with Oxfendazole (OXF) 15 days
      after dosing. Group 2 received only OXF. After the third dose of OXF, the goats
      were grazed together on the same pasture and fecal egg counts determined. No
      protection in immunized goats was achieved. In fact, immunized goats produced
      significantly more nematode eggs than the nonimmunized group.

PMID- 9194843
TI  - Parasite antigen-induced IFN-gamma and IL-4 production by cells from
      pathopermissive and pathoresistant strains of mice infected with Trypanosoma
      cruzi.
AB  - The cardiac pathology associated with infection by Trypanosoma cruzi in mice has
      been suggested to be partially dependent upon cytokine responses. The
      pathoresistant B10.D2 mice, which display little infection-induced myocarditis,
      and the pathopermissive DBA/2 mice, which show significant cardiac damage, were
      compared for their in vitro interferon (IFN)-gamma and interleukin (IL)-4
      production. Concanavalin A-stimulated spleen cells from infected B10.D2 mice
      produce a greater amount of IFN-gamma than DBA/2 mice, whereas the IL-4
      production is only slightly greater in the B10.D2 mice than the DBA/2 mice.
      Parasite antigen stimulation of spleen cells from these mice results in a clearly
      greater IFN gamma production by the B10.D2 and a higher IL-4 level for the DBA/2
      mice. The data presented suggest a relationship between an enhanced TH1-type
      response and decreased chronic cardiac pathogenesis, whereas a lower level of TH1
      activity may play a role in cardiac involvement.

PMID- 9194844
TI  - The prevalence of cercariae from Stagnicola emarginata (Lymnaeidae) over 50 years
      in northern Michigan.
AB  - Stagnicola emarginata were collected from 3 northern Michigan lakes and examined
      for larval trematode infections. The structure of the trematode community was
      then compared with 2 previous studies conducted on Douglas Lake in order to
      determine what changes had taken place over a period of more than 50 yr and to
      examine the possibility of using trematodes as bioindicators of environmental
      quality. Species richness was reduced by half (from 16 to 8 species) from the
      first study conducted in 1936, along with a decrease in the overall prevalence
      from 61% to 13%. No new species had colonized the lake, and the same 8 trematodes
      were also the only species found in 2 other lakes. The decline in prevalence was
      most severe in trematodes that used gulls as definitive hosts, whereas species
      that used ducks as hosts increased slightly. The decrease in species richness and
      prevalence of infection over time may reflect increasing human impacts on lakes.
      However, because of patchy host distributions, the use of larval trematodes as
      bioindicators of environmental change requires further investigation.

PMID- 9194845
TI  - Acanthocephala of the bald eagle (Haliaeetus leucocephalus) in North America.
AB  - Examination of bald eagles (Haliaeetus leucocephalus) collected from several
      locations in North America contributed new information concerning the
      acanthocephalan fauna of this host. Representatives of Arythmorhynchus brevis,
      representing a new host record, were collected from eagles in Florida, New
      Hampshire, and Wisconsin. Plagiorhynchus sp. was collected from an eagle in
      Florida. Corynosoma strumosum was collected from an eagle in Alaska. Andracantha
      phalacrocoracis, representing a new host record, was collected from an eagle in
      Alaska. Southwellina hispida, representing a new host record, was collected from
      eagles in Maine and Virginia. The occurrence of gravid or mature females of A.
      brevis, Plagiorhynchus sp., and S. hispida suggests that the bald eagle may serve
      as a competent definitive host for these species.

PMID- 9194846
TI  - Copulation and sexual congress of Leptorhynchoides thecatus (Acanthocephala).
AB  - Pairs of the acanthocephalan Leptorhynchoides thecatus from laboratory infections
      were observed copulating at 21 days, 5 wk, and 12 wk postinfection (PI) in green
      sunfish, Lepomis cyanellus. Additionally, copulating pairs of worms from natural
      infections were observed. In each instance of paired males and females, the male
      was in 1 pyloric cecum of the fish and the female in another. Each had its
      posterior end protruding into the intestinal lumen at the point from which the
      ceca arise. The completely extruded bursa of the male fully enclosed the
      posterior end of the female in a firm attachment. In 1 instance at 5 wk PI, 2
      males were observed in copula. One male had its copulatory bursa completely
      retracted, and the copulatory bursa of the other male was positioned just as
      though the mate were a female. Based on these and previous findings, it is
      concluded that male acanthocephalans mate indiscriminately and often throughout
      their lives. Habitation of ceca maximizes sexual congress because individuals
      often are positioned with their posterior ends extending into the intestinal
      lumen within the small area from which ceca originate. Emigration to find a mate
      is unnecessary.

PMID- 9194847
TI  - Adaptive sex-ratio manipulation in Pediculus humanus capitis: possible
      interpretations of Buxton's data.
AB  - The sex-ratio pattern of an exceptional population of human head lice (collected
      in the Colombo Prison, Ceylon, in 1934 to 1936) was found to be consistent with a
      current hypothesis on adaptive sex-ratio manipulation. Data suggest that the
      louse burdens were isolated and, therefore, small burdens were inbred. Thus,
      local mate competition favored females that produced offspring with a female
      bias. This is the first report to suggest that anopluran lice are capable of
      adaptive sex-ratio manipulation.

PMID- 9194848
TI  - Serological diagnosis of bovine fetal neosporosis.
AB  - To evaluate the efficacy of fetal serology in the diagnosis of bovine neosporosis
      abortion, sera from 48 fetuses with immunohistochemically confirmed neosporosis
      and 42 fetuses without demonstrable Neospora caninum were examined in the
      indirect fluorescent antibody test (IFAT). Fetal sera were diluted 2-fold
      starting at a 1:25 dilution. Antibodies to N. caninum were detected in 31 of 48
      (65%) fetuses with confirmed neosporosis; the IFAT antibody titers were 1:25 (5
      fetuses), 1:50 (17 fetuses), 1:200 (6 fetuses), and > or = 1:800 (3 fetuses).
      Neospora caninum antibodies were found in 3 of 42 fetuses without demonstrable
      protozoa; in all 3 cases, a high titer was found suggesting undiagnosed
      congenital neosporosis. A recombinant antigen enzyme-linked immunosorbent assay
      was not useful for the detection of fetal antibodies to N. caninum.

PMID- 9194849
TI  - Transmission of the Lyme disease spirochete, Borrelia garinii, between infected
      and uninfected immature Ixodes persulcatus during cofeeding on mice.
AB  - The ixodid tick, Ixodes persulcatus, serves as a vector for the Lyme disease
      spirochete, Borrelia garinii, in Japan. Transmission of the spirochete from
      infected nymphs to uninfected larvae during their cofeeding on mice was studied
      under laboratory conditions. Using feeding chambers, infected nymphs and
      uninfected larvae were allowed to cofeed on heads of normal BALB/c mice. In
      another group of mice, we separately exposed nymphs to the head and larvae to the
      back. The resultant engorged larvae were reared and the molted nymphs were
      examined for spirochetes. Spirochetal infections were found only in ticks that
      had fed together with infected ticks. The data strongly suggest that spirochetes
      can migrate from infected feeding ticks to their uninfected neighbors by way of
      host skin. Moreover, nymphs that had become infected through the cofeeding
      process could transmit spirochetes to mice.

PMID- 9194850
TI  - Chromosome number of Trichomonas vaginalis.
AB  - Chromosome number of an axenically grown Trichomonas vaginalis isolate was
      studied using a 1 mM solution of colchicine and a hypotonic swelling technique.
      The diploid chromosome number was 2n = 6 [corrected]. Each pair of chromosomes
      can be identified by its morphology and size. This observation could be important
      with respect to gene mapping and molecular cloning for genes of T. vaginalis.

PMID- 9194851
TI  - Assay for phenoloxidase activity in Amblyomma americanum, Dermacentor variabilis,
      and Ixodes scapularis.
AB  - Phenoloxidase activity in Amblyomma americanum, Dermacentor variabilis, and
      Ixodes scapularis was assayed. No phenoloxidase activity was detected compared to
      high activity through time in larvae of the greater wax moth (Galleria
      mellonella). We conclude that activated prophenoloxidase does not act as an
      opsonin in ixodid ticks tested to date.

PMID- 9194852
TI  - Most anchoring fibrils in human skin originate and terminate in the lamina densa.
AB  - Anchoring fibrils (AF) at the dermo-epidermal junction are well characterized as
      ultrastructural entities. They are composed mainly of collagen VII and play a key
      role in dermo-epidermal adhesion. Previous studies have suggested that AF
      originate in the lamina densa (LD), extend perpendicularly into the dermis, and
      insert into amorphous elements, called "anchoring plaques," in the dermal
      connective tissue. To elucidate the precise structural organization of the AF
      network in human skin, we analyzed quantitatively the distribution of different
      domains of collagen VII in the epidermal basement membrane zone, using various
      techniques of immunoelectron microscopy with a range of domain-specific
      antibodies that we prepared. Some electron-dense amorphous structures (ie,
      anchoring plaques) that were positive with aminoterminal end of collagen VII
      could be recognized only by pre-embedding en bloc labeling, and not by
      postembedding section labeling of immunoelectron microscopy. Quantitative
      analysis of surface labeling with postembedding immunoelectron microscopy
      demonstrated that most (> 90%) gold particles labeling the epitopes in the
      aminoterminal (NC-1 domain) of collagen VII were precisely localized to the LD,
      whereas no specific labeling was observed in the dermis. Most (> 90%) of the gold
      particles labeling the carboxyterminal end of collagen VII localized at a 160- to
      360-nm distance from the LD, and most (> 90%) of the labeling epitopes in the
      central triple-helical collagenous domain were distributed between the LD and up
      to 360 nm from it; no specific labelings were observed beyond this area. These
      results suggest that most (> 90%), if not all, of the AF in human skin do not
      extend perpendicularly into the dermis, but instead originate and terminate in
      the LD, forming individual semicircular loops that constitute a network of AF.

PMID- 9194853
TI  - Extracellular matrix deposition, lysyl oxidase expression, and myofibroblastic
      differentiation during the initial stages of cholestatic fibrosis in the rat.
AB  - Early studies showed that during hepatic fibrosis induced by bile duct ligation,
      fibroblasts within the portal tracts proliferate and express alpha-smooth muscle
      (SM) actin, suggesting that they may be involved in the deposition of
      extracellular matrix components in cholestatic fibrosis. Thus, we investigated
      the deposition of extracellular matrix components (laminin, fibronectin EIIIA,
      collagen I and IV, procollagen III, elastin, tenascin) as well as the expression
      of lysyl oxidase and of alpha-SM actin in the portal zone at 24, 48, and 72 hours
      and 7 days after ligation of the common bile duct. Rat liver tissues were
      processed for immunofluorescence, in situ hybridization, immunohistochemistry,
      and for electron and immunoelectron microscopy. At all times examined after bile
      duct ligation, laminin was observed essentially in the basal membrane of vessels
      and portal ductules. In sham-operated animals, the fibronectin EIIIA was present
      exclusively in vessels; at 24 hours postinjury, fibronectin EIIIA expression
      appeared in both the portal zone and along sinusoids. Two days after ligation,
      increased expressions of collagen I and IV, procollagen III, and elastin were
      observed within the portal zone, compared with sham-operated animals. The
      deposition of these components increased thereafter. Tenascin expression
      increased soon after bile duct ligation in stroma surrounding proliferating
      ductules, reaching a maximum at 48 hours; thereafter, expression was restricted
      to the periphery of proliferating ductules. By in situ hybridization, procollagen
      I and tissue inhibitor of metalloproteinase-1 mRNA expression was greatly
      increased in periductular areas at 24 hours postligation and remained elevated
      throughout the experiment. At 24 hours, a strong reactivity for lysyl oxidase
      appeared in the portal zone, and, as in controls, alpha-SM actin expression was
      restricted to vascular SM cells. In the stroma adjacent to proliferating
      ductules, alpha-SM actin appeared at 48 hours, and the number of alpha-SM actin
      positive cells increased until the 7th day. Lysyl oxidase staining increased
      until 72 hours after bile duct ligation, when it was located in areas surrounding
      the myofibroblastic cells. At 7 days, lysyl oxidase expression was restricted
      around myofibroblastic cells present at the periphery of the reactive tissue and
      appeared to extend into the surrounding parenchyma. These results show that after
      bile duct ligation, extracellular matrix deposition, and lysyl oxidase expression
      occur very early in portal connective tissue surrounding proliferating ductules,
      and precede myofibroblastic differentiation, ie, alpha-SM actin expression. In
      addition, the data are compatible with the suggestion that in the bile duct
      ligation model, myofibroblastic differentiation represents an adaptive response
      to modification of the extracellular matrix environment.

PMID- 9194854
TI  - Role of VEGF receptor-1 (Flt-1) in mediating calcium-dependent nitric oxide
      release and limiting DNA synthesis in human trophoblast cells.
AB  - Vascular endothelial growth factor (VEGF) receptor KDR (kinase-insert-domain
      containing receptor) is linked to endothelial cell proliferation, and VEGF
      receptor Flt-1 (fms-like tyrosine kinase) is essential for the organization of
      embryonic vasculature. Flt-1 is also known to be expressed on adult endothelial
      and trophoblast cells, although its function has not yet been established. Herein
      we report that human trophoblast and endothelial cells contain functional Flt-1
      receptors for VEGF that trigger the synthesis and release of nitric oxide (NO) by
      the activation of constitutive NO synthase (cNOS). In first-trimester human
      trophoblast cells isolated by chorionic villous sampling, VEGF165 stimulated NO
      release in a concentration- and time-dependent manner, with a maximal increase of
      60% (in comparison to basal release levels) occurring within 30 minutes (basal:
      1342 pmol/ml; VEGF (10 ng/ml): 2162 pmol/ml; p < 0.001), as measured by an NO
      chemiluminescence analyzer. VEGF20, a peptide fragment that is composed of the
      first 20 amino acids at N-terminus, displayed properties of a partial agonist.
      VEGF165- and VEGF20-mediated NO biosynthesis was attenuated by NG-nitro-L
      arginine in a concentration-dependent fashion, indicating NOS activation. VEGF
      neutralizing anti-VEGF monoclonal antibody significantly inhibited VEGF-mediated
      NO release (p < 0.001), and the addition of a neutralizing anti-Flt-1 antibody
      inhibited the response by 79.6% +/- 7.59%, an effect found to be reversible with
      higher concentrations of VEGF. In contrast, anti-KDR antibody had no significant
      inhibitory effect. RT-PCR confirmed the presence of mRNA encoding the Flt-1 and
      KDR receptors as well as the endothelial form of cNOS in trophoblast cells.
      VEGF165-stimulated NO release was inhibited by genistein (5 microM; p < 0.001) as
      well as by the removal of calcium from the extracellular environment (p < 0.001),
      which suggests the contingency of this process on tyrosine phosphorylation and
      extracellular calcium, respectively. Addition of sodium nitroprusside, an NO
      donor, inhibited trophoblast DNA synthesis in a concentration-dependent manner,
      as measured by [3H]thymidine incorporation, without affecting cell viability.
      VEGF under maximal NO production had no mitogenic activity, suggesting that
      trophoblast-derived NO may limit trophoblast proliferation. Endogenous
      trophoblast DNA synthesis increased 3-fold in the presence of anti-Flt-1 antibody
      but not in the presence of anti-KDR antibody, suggesting that Flt-1 functions as
      a growth suppressive receptor to counteract the proliferative actions of KDR.
      Levels of immunoreactive endothelial cNOS were markedly increased in growth
      restricted placentae (n = 4) in comparison to those of normal (n = 5) placentae,
      which may account for the relatively small-sized placentae associated with
      intrauterine growth restriction. VEGF165 stimulated NO release via
      phosphorylation of the Flt-1 receptor, indicating that VEGF may be an autocrine
      regulator of NO biosynthesis by aiding trophoblast penetration into spinal
      arterioles during the first trimester and preventing platelet aggregation within
      the placenta. Finally, the activation of Flt-1 receptor suppressed trophoblast
      DNA synthesis within the placenta via NO.

PMID- 9194855
TI  - Clonal versus polyclonal Epstein-Barr virus infection in nasopharyngeal carcinoma
      cell lines.
AB  - In most nasopharyngeal carcinoma (NPC) biopsy specimens, the Epstein-Barr virus
      (EBV), particularly in the terminal repeat region genomic structure, reveals a
      clonal pattern. To evaluate this phenomenon in vitro, we infected EBV-negative
      NPC cell lines, which express secretory component (SC) protein on their cell
      surface, with EBV particles. The viral particles were obtained either from a
      subcloned single cell or from the original B95-8 cell line. EBV infection was
      performed by incubating IgA anti-EBV and EBV particles with NPC cells and
      confirmed by direct in situ PCR hybridization. Southern blot analysis of EBV
      terminal repeat in EBV-infected NPC cell lines was performed using a Xhol 1.9-kb
      DNA fragment from the right terminus of the EBV genome as a probe. We found that
      all four NPC cell lines (ie, NPC-TWO1; 03, 04, and 06) expressed SC protein on
      their surfaces and could be infected by EBV through the EBV IgA-SC complex.
      Southern blot analysis in the single cell-subcloned B95-8 cell line showed a
      clonal EBV terminal repeat with a higher molecular size; whereas the original B95
      8 line revealed the polyclonal EBV DNA pattern. A similar clonal EBV genomic
      pattern with lower molecular size was seen in all EBV-infected NPC cell lines.
      For comparison, six NPC biopsy specimens were also examined; of these, five
      showed a single band, and the remaining showed one major band and several lower
      molecular-sized bands. The EBV genomic DNA in the infected cells was shown to be
      an episomal form. We conclude, therefore, that a single (clonal) form of EBV
      genome can be obtained from a mixed population of epithelial tumor cells, even
      when they are infected by multiple virions with single or multiple form(s) of the
      EBV genomic pattern.

PMID- 9194856
TI  - Decision tree induction: a useful tool for assisted diagnosis and prognosis in
      tumor pathology.
AB  - The aim of the present work is to show that decision tree induction algorithms
      are a useful tool for extracting reliable information from data series, with the
      objective of assisting pathologists in identifying specific diagnostic and
      prognostic markers in various types of tumor pathologies. In terms of accuracy,
      we show that the decision tree technique exceeds other more sophisticated
      techniques, such as multilayer neural networks. Furthermore, because of the case
      with which decision tree results can be interpreted (logical classification
      rules), new methodologies can be readily developed to further assist in analyzing
      complex data that mix heterogeneous features. In this paper, we illustrate such
      capabilities in the context of different complex diagnostic and/or prognostic
      problems in tumor pathology relating to bladder, astrocytomas, and adipose
      tissues.

PMID- 9194857
TI  - Leukocyte kinetics in the pulmonary microcirculation: observations using real
      time confocal luminescence microscopy coupled with high-speed video analysis.
AB  - To quantitatively assess blood cell kinetics in the intact pulmonary
      microcirculation, in which arterioles, venules, and capillaries are exceedingly
      intricate and densely convoluted, we recently developed a real-time confocal
      laser luminescence microscope with a high-speed analysis component. The system
      has the capacity to yield confocal images of rapidly moving cells at a rate of
      1000 frames/second and at sufficiently high degrees of magnification. Applying
      this novel method to isolated perfused rat lungs, we estimated the endothelial
      distributions of constitutively expressed intercellular adhesion molecule-1 (ICAM
      1) and P-selectin and also studied leukocyte hemodynamic behavior in the
      pulmonary microvasculature under conditions in which ICAM-1, P-selectin, and L
      selectin were inhibited, respectively, by 1A29 (monoclonal antibody to rat ICAM
      1), ARP2-4 (monoclonal antibody to rat P-selectin), and fucoidin (competitive
      inhibitor of both P- and L-selectin). The results were compared with those
      obtained with a nonconfocal microscope using conventional epiluminescence.
      Intertwined microvessel networks in the lung were clearly distinguishable in
      confocal images but not in conventional nonconfocal views. ICAM-1 was perceptibly
      expressed along venular and capillary but not arteriolar endothelium, whereas P
      selectin was undetectable in all microvessels examined. Leukocytes were not
      firmly adhered to venular or arteriolar endothelial cells. Leukocyte rolling was
      recognized more frequently along arteriolar walls than along venular walls and
      was suppressed in arterioles by L-selectin inhibition but not by either ICAM-1 or
      P-selectin inhibition. In capillaries, transient and sustained arrest of
      leukocytes occurred at physiologic shear rates. Inhibition of ICAM-1 or P
      selectin had no remarkable effect upon either transient or sustained entrapment
      of leukocytes in capillaries. In conclusion, physiologic and biologic
      characteristics of pulmonary microvessels appear to be quite different from those
      of the systemic microcirculation.

PMID- 9194858
TI  - Genomic organization of the integrin beta 4 gene (ITGB4): a homozygous splice
      site mutation in a patient with junctional epidermolysis bullosa associated with
      pyloric atresia.
AB  - Integrin beta 4 is expressed primarily within the epithelial basement membranes,
      and it contributes to the stable association of epidermis with the underlying
      basement membrane. Previous observations have suggested that the expression of
      this integrin, which is alternatively spliced in various cell types, is deficient
      in a variant of junctional epidermolysis bullosa associated with pyloric atresia
      (JEB-PA). To facilitate identification of mutations in the human beta 4 integrin
      gene, ITGB4, we have now determined its intron-exon organization. The entire gene
      was shown to consist of 41 exons spanning 36 kb of the genomic DNA on chromosome
      17q11-qter. The mutation detection, using PCR-amplification of each exon followed
      by heteroduplex analysis, revealed a homozygous splicing mutation in a patient
      with JEB-PA. RT-PCR revealed the presence of two splice variants generated
      through utilization of cryptic splice sites, and both mRNA transcripts resulted
      in a frame-shift and premature termination codon of translation. The presence of
      the mutation resulted in dramatic reduction of the corresponding mRNA transcript
      level. Because beta 4 integrin is expressed not only in the skin but also in the
      epithelial lining of the stomach, the absent expression of this integrin in the
      proband may explain the blistering tendency and development of pyloric atresia.

PMID- 9194859
TI  - Acceleration of atherosclerotic lesions in transgenic mice with hypertension by
      the activated renin-angiotensin system.
AB  - The present study was designed to investigate the development of atherosclerotic
      lesions in hypertensive transgenic mice carrying both the human renin and
      angiotensinogen genes (Tsukuba hypertensive mice; THM). THM and C57BL/6J control
      mice 2 to 3 months of age were fed with either an atherogenic or a normal diet
      for 14 weeks. Although the systolic blood pressure of either strain remained the
      same regardless of diet, it was significantly higher in THM than in C57BL/6J on
      both diets. Total plasma cholesterol concentrations in mice on the atherogenic
      diet were significantly higher than those in mice fed the normal diet.
      Lipoprotein profiles of cholesterol in THM were fundamentally similar to those in
      C57BL/6J on either the atherogenic or normal diet. Compared with controls,
      however, microscopic analyses revealed accelerated damage of cellular structure
      in the aortic root in THM fed with the atherogenic diet. Remarkably, the surface
      area of atherosclerotic lesion in THM was shown by quantitative image analysis to
      be 4 times larger than that in C57BL/6J on the same atherogenic diet. These
      findings suggested that hypertension induced by the activated renin-angiotensin
      system is involved in the development of atherosclerotic lesions. Therefore, THM
      should be a useful animal model for the study on the pathogenesis of
      atherosclerosis.

PMID- 9194860
TI  - Stromal and vascular invasion in an human in vitro bladder cancer model.
AB  - In transitional cell carcinoma (TCC) of the urinary bladder, disease spread may
      occur through local invasion of the bladder wall and/or via hematogenous
      dissemination. Although the metastatic phenotype is well studied, little is known
      about the mechanisms that determine and regulate secondary dispersion via stromal
      and vascular routes. The aim of this study was to develop an in vitro system to
      study TCC invasion using normal human urinary tract stroma in organ culture.
      Human de-epithelialized urinary tract stromas were seeded with established human
      TCC cell lines (RT4, RT112, and EJ) and maintained in organ culture at an air
      liquid interface for up to 8 weeks. The composite tissues were analyzed
      immunohistochemically using antibodies to a proliferation-associated antigen,
      cell adhesion molecules, extracellular matrix components, and cytokeratin
      isotypes. The phenotype of TCC cell lines maintained as monolayer cultures were
      compared with the composite tissues to assess the regulatory effects of the
      stroma. On a normal urothelial stroma, the TCC cell lines proliferated and
      underwent a degree of differentiation related to the grade of the original tumor.
      RT4 cells formed a stratified epithelium with low proliferation, some
      characteristics of urothelial differentiation, and no evidence of stromal
      invasion over the 8-week culture period. RT12 cells formed a stratified
      epithelium with limited differentiation and by 2 weeks showed intravasation of
      the subepithelial capillary bed. Anaplastic EJ cells did not stratify but
      diffusely invaded the stromal matrix and the superficial vasculature. In
      conclusion, the urothelial stroma can support cytodifferentiation in vitro and
      influence the behavior of malignant TCC cells. The model has application for
      determining genetic and epigenetic factors that influence whether a tumor
      progresses by local and/or hematogenous spread. Furthermore, it may offer a
      useful approach in evaluating prognostic and diagnostic markers and strategies
      for preventing invasion.

PMID- 9194861
TI  - Genetic immunization with the free human chorionic gonadotropin beta subunit
      elicits cytotoxic T lymphocyte responses and protects against tumor formation in
      mice.
AB  - The free beta subunit of human chorionic gonadotropin (hCG beta) is produced and
      secreted by human lung, bladder, and pancreatic tumors. We attempted to generate
      cytotoxic T lymphocytes (CTL) with activity against free hCG beta-producing
      tumors by genetic immunization using a construct containing a beta subunit
      expressing cDNA. To assess CTL activity in vivo, a cloned syngeneic SP2/O myeloma
      call line was established that constitutively expresses the free hCG beta
      protein. Inoculation of this cell line into BALB/c mice produced large tumors
      within 2 weeks. However, mice immunized with the free hCG beta expression
      construct demonstrated a marked reduction of tumor size and weight compared with
      animals immunized with mock DNA ("empty" plasmid). Indeed, 30% of immunized mice
      were tumor-free after 3 months and thus considered long-term survivors.
      Inhibition of tumor growth was strongly associated with the level of CTL activity
      present in CD8+ cells derived from the spleen. In addition, immunized mice
      developed high titer anti-hCG beta antibodies that neutralized the biologic
      effects of the intact hCG glycoprotein hormone on its cellular receptor as well.
      These results illustrate that substantial cellular and humoral immune responses
      to the free hCG beta subunit may be generated by DNA immunization. This study
      thus presents a potential approach to inhibiting growth of human tumor cells that
      produce and secrete the free hCG beta protein.

PMID- 9194863
TI  - Betting on favorites.

PMID- 9194864
TI  - Junk on the Web.

PMID- 9194862
TI  - Physician assistance in dying.

PMID- 9194865
TI  - Is it Alzheimer's disease?
AB  - According to one estimate, Alzheimer's disease has been diagnosed in more than 4
      million Americans. As our population continues to age, we can expect to see a
      sharp increase in this number. By the middle of the next century, there are
      projected to be almost as many Americans over age 80 as there now are over age
      65. Primary care physicians are bound to see more and more patients who appear to
      have Alzheimer's disease, and the burden is on them to rule out other, treatable
      forms of dementia. Dr. Gambert describes how to distinguish the true cognitive
      dysfunction of Alzheimer's disease and where to go from there.

PMID- 9194866
TI  - After the diagnosis.
AB  - When the words "Alzheimer's disease" are first used regarding a patient with
      increasing memory and judgment problems, the person involved and his or her
      family members usually leave the office with sinking hearts. However, Dr. Ham
      believes that using the term is important, because it gives structure to
      management and can be the impetus to seek information about the disease and learn
      about local support organizations. Clarifying the diagnosis is but the first of
      many ways that primary care physicians can assist families in deciding about home
      care, intensity of treatment, and long-term placement.

PMID- 9194867
TI  - Treating Alzheimer's disease. Pharmacologic options now and in the near future.
AB  - Treatment of Alzheimer's disease has in the past been limited to empirical trials
      of psychotropics for relief of behavioral complications. At present, tacrine and
      doneprezil are the only FDA-approved antidementia agents available. In the very
      near future, however, other cholinesterases inhibitors (e.g., ENA 713,
      metrifonate, long-acting physostigmine) are expected to be approved for clinical
      use. The evidence at this point suggests that they have modest but meaningful
      clinical effects and possible long-term benefits. Clinical use of the newer
      agents is likely to be influenced by their side-effect profiles, which consist
      largely of cholinergic effects, although without the hepatotoxic effects
      associated with tacrine. To what extent these agents are accepted by patients and
      physicians remains to be seen. On the one hand, benefits are modest; on the
      other, these medications are increasingly safe. Continuing research is clarifying
      the role of cholinergic therapy in relieving behavioral symptoms, as well as the
      possible side effects on rates of illness progression, institutionalizaton, and
      even mortality. In the not-too-distant future, physicians can expect to see a
      variety of medications, now in early stages of development, that are intended to
      affect cholinergic systems in other ways. Further down the road, a host of
      mechanism-based therapeutic strategies, which hope to deal with the first cause
      of this devastating illness, will have been assessed in clinical trials.

PMID- 9194868
TI  - Dermatitis of the feet.
AB  - Most rashes that occur on the feet are due to eczema, infections, or shoe
      dermatitis. But which are which? Fortunately, distinguishing among these common
      skin diseases requires just a little basic knowledge of dermatology and
      familiarity with two simple diagnostic tests. Two case reports illustrate the
      authors' approach to diagnosis, treatment, and patient education.

PMID- 9194869
TI  - Transdermal estrogen therapy.
AB  - Estrogen replacement therapy is becoming an important weapon in the fight against
      osteoporosis and heart disease in postmenopausal women, in addition to its
      original role of alleviating many of the symptoms associated with menopause. Dr.
      Connell discusses the many benefits of estrogen replacement therapy and the
      advantages that transdermal administration of estrogen appear to offer over other
      routes of administration.

PMID- 9194870
TI  - Cutaneous clues to systemic disease.
AB  - Scleroderma, psoriasis, lichen planus, and other skin disorders may signal a more
      serious internal disease. Physicians who recognize such clues can initiate early
      treatment while disease is in its early stages. The authors of this article
      describe several of the more common dermatologic conditions linked to systemic
      disease, including connective tissue, inflammatory, immunobullous, and infectious
      diseases.

PMID- 9194871
TI  - Vaccines and the power of immunity.

PMID- 9194872
TI  - Adults who snore.
AB  - Snoring is a common finding in adults and may signal sleep-disordered breathing.
      Careful history taking and physical examination may identify patients who require
      polysomnography. Any snoring that is disruptive to a patient's life or
      accompanied by symptoms suggesting obstructive sleep apnea requires further
      evaluation. Ambulatory polysomnography may be adequate in asymptomatic snorers
      (i.e., those without witnessed apneic episodes, daytime sleepiness, or
      significant associated disease processes) who seek treatment for social reasons.
      Split-night testing is a promising diagnostic protocol for symptomatic snorers.
      All snorers benefit from instruction on behavior modification. The best treatment
      option (fitting of an oral appliance, surgical intervention, CPAP) depends on
      whether apneic episodes accompany snoring and on patient preference. More studies
      are needed to determine the most reliable and cost-effective approach to
      symptomatic snoring.

PMID- 9194873
TI  - Treating empyema without surgery.
AB  - Normally, the pleural spaces contain sterile lubricating fluid that enables
      smooth expansion and contraction of the lungs. But when microorganisms gain
      entry, directly or through contiguous spread of infection, the fluid becomes
      increasingly dense and viscous as purulence progresses. This article outlines
      clinical, radiographic, and pleural fluid features that can aid in distinguishing
      between pleural collections that usually respond to medical therapy and those
      that probably require surgical intervention.

PMID- 9194874
TI  - Adolescent idiopathic scoliosis.
AB  - Although the majority of patients with adolescent idiopathic scoliosis do not
      require more than observation, some may indeed need brace therapy or surgery. How
      do you identify those in whom further investigation or referral is warranted? Dr.
      Haasbeek reviews methods of clinical detection, available treatment options, and
      appropriate use of each treatment based on the natural history of the disorder.

PMID- 9194875
TI  - Human ehrlichiosis.
AB  - Ten years ago, tick-borne ehrlichiosis infection was primarily a problem in dogs,
      cattle, and sheep. Today hundreds of people have been infected by newly
      recognized Ehrlichia species. If infection is detected early, treatment is
      relatively simple and usually effective. Late diagnosis, on the other hand,
      carries serious morbidity or even death. Dr. Glushko discusses the history,
      epidemiology, and clinical aspects of human ehrlichiosis and provides information
      on both treatment and prevention.

PMID- 9194876
TI  - Urinary tract infections.
AB  - Management of urinary tract infections may seem quite straightforward, but the
      patient's age, gender, and other factors can affect management and outcome.
      Appropriate management can forestall recurring problems and lead to a better
      quality of life. Dr. Schleupner reviews special situations and outlines treatment
      options for those cases where individualized care is important.

PMID- 9194877
TI  - Celiac disease.
AB  - Celiac disease, or gluten-sensitive enteropathy, classically presents as diarrhea
      and weight loss in childhood, but it may also have protean manifestations and
      appear well into adult life. The increasing availability of noninvasive blood
      tests that are highly sensitive and specific for celiac disease enables primary
      care physicians to recognize the disorder in a wide variety of clinical
      situations. The authors believe that the disease is more common than supposed and
      thus offer this diagnostic review to increase awareness.

PMID- 9194878
TI  - General principles of wound healing.
AB  - Wound healing is a complex process involving different biologic and immunologic
      systems. Despite improvements in diagnostics and therapy, wound failures remain a
      clinical problem. The approach to a nonhealed wound is an interdisciplinary
      challenge that should not be underestimated. Better understanding of the complex
      wound-healing cascade helps our approach to wound healing and its possible
      failure. Manipulations of the involved immunologic features offer future
      therapeutic strategies.

PMID- 9194879
TI  - Healing in other tissues.
AB  - Wound healing in many tissue types is essentially the same as that which occurs
      in skin. The repair processes that occur in bone, tendon, the alimentary tract,
      skin grafts, and bone grafts are substantially different from cutaneous wound
      repair. Because surgeons frequently encounter these tissues, it is essential to
      understand how they heal.

PMID- 9194880
TI  - Healing in the gastrointestinal tract.
AB  - Healing in the GI tract is rapid when free of complications: Unlike cutaneous
      healing, in which progress can be observed on a daily basis and intervention
      instituted early if necessary, healing of the intestinal anastomosis is
      anatomically obscured from inspection, allowing the surgeon only the patient's
      parameters of general well-being to judge the success of the operation. For the
      same reason, complications usually require re-operation, with the associated
      morbidity of a laparotomy and additional general anesthetic. This places a great
      responsibility on the surgeon to be cognizant of all the preoperative,
      intraoperative, and postoperative factors relating to anastomotic healing that
      might compromise the healing process. Bearing these in mind, along with attention
      to technical detail, should limit complications to an acceptable level. Patients
      most at risk are (1) those who perioperatively develop physiologic problems that
      lead to shock, hypoxia, and resultant anastomotic ischemia, (2) those with
      radiation-induced tissue injury, (3) those with sepsis, and (4) those with
      preoperative bowel obstruction. Malnourishment, malignancy, diabetes, steroids,
      and age also influence outcome to varying degrees. Future advancement in the
      field of GI healing lies in our ability to manipulate the early struggle between
      collagen synthesis and collagen breakdown. A profound understanding of the
      molecular and biochemical pathways and the factors that control them will bring
      us closer to this goal. Clinically, this may be accomplished by the introduction
      of wound healing enhancers into the anastomotic site, possibly by incorporating
      them into suture materials, biofragmentable anastomotic rings, or staple
      materials. Already much is known about the influence of different cytokines and
      growth factors on collagen regulation, knowledge that will help resolve many of
      the long-standing problems associated with GI surgery.

PMID- 9194881
TI  - The role of growth factors in wound healing.
AB  - Growth factors applied topically to wounds can accelerate healing by stimulating
      granulation tissue formation and enhancing epithelialization. This has been
      suggested by several different studies of topically applied growth factors. It is
      clear, however, that topical growth factor therapy should not be considered as a
      substitute for good wound care, including surgical debridement or
      revascularization.

PMID- 9194882
TI  - Wound healing and wound infection. What surgeons and anesthesiologists can do.
AB  - Wound healing can be enhanced and wound infections prevented, often by simple,
      inexpensive, readily available means. Preoperative evaluation for impediments to
      healing, such as malnutrition, vasoconstriction, hyperglycemia, and steroid use,
      allows correction prior to operation. Intraoperatively, the surgeon should
      concentrate on surgical technique, appropriate antibiotic use, and prevention of
      vasoconstriction (volume, warming). Postoperatively, the focus should be on
      prevention of vasoconstriction through pain relief, warming, and adequate volume
      resuscitation and on maintaining nutrition and normoglycemia. These approaches
      apply as well to chronic wounds. Additionally, maintenance of a moist
      environment, correction of local vasospasm with sympathetic blockade or warming,
      and stimulation of angiogenesis through aggressive debridement or hyperbaric
      oxygen therapy enhance healing of chronic wounds.

PMID- 9194883
TI  - Acute wound failure.
AB  - The causes and treatment of acute failure of the abdominal incision are reviewed,
      along with a summary of studies on fascial healing. Emphasis is placed on taking
      large bites of tissue during closure to prevent dehiscence. Patient-related risk
      factors are viewed as less important in the causation of wound failure.

PMID- 9194884
TI  - Wound infection. A failure of wound healing caused by an imbalance of bacteria.
AB  - Infection in a wound, like infection elsewhere in the body, is a manifestation of
      a disturbed host-bacteria equilibrium in favor of the bacteria. This not only
      elicits a systemic septic response but actually inhibits the multiple processes
      involved in the wound healing scheme. Each process involved in healing is
      affected when bacteria proliferate in a wound. Wound infection, whether in an
      intentional operative incision, an acute traumatic laceration, or a chronic
      pressure ulcer, results when bacteria indigenous to the patient or exogenous to
      the wound achieve dominance over the systemic and local factors of host
      resistance. To be able to prevent and manage wound infections requires an
      understanding of how each prophylactic or therapeutic maneuver works to maintain
      or re-establish the bacteria-host balance. Only when this equilibrium is in
      balance can the normal processes of wound healing proceed to give a satisfactory
      healing trajectory.

PMID- 9194885
TI  - The role of sutures and fibrin sealant in wound healing.
AB  - Sutures and fibrin sealant are important surgical aids for facilitating wound
      closure and creating an optimal setting for wound healing. Most commonly, sutures
      are used to close wounds because suture material provides the mechanical support
      necessary to sustain closure. A wide variety of suturing material is available,
      and the surgeon can choose among sutures with a range of attributes to find the
      one best suited to his or her needs. Considerations when choosing an appropriate
      suture for wound closure and healing include strength of suture, holding power of
      tissue, absorbability, risk of infection, and inflammatory reaction associated
      with the suture material. Other factors to be considered include type of
      incision, suturing technique, and appearance of wound site. Fibrin sealant, in
      contrast, is a biologic tissue adhesive that can function as a useful adjunct to
      sutures. Fibrin sealant can be used in conjunction with sutures or tape to
      promote optimal wound integrity, or it can be used independently to seal wound
      sites where sutures cannot control bleeding or would aggravate bleeding. This
      adhesive can effectively seal tissue planes and eliminate potential spaces.
      Fibrin sealant has been used clinically in many surgical applications, although
      an FDA-approved commercially available product does not yet exist in the United
      States. Clinically, fibrin sealant has resulted in a low rate of infection and
      has promoted healing. Further study is needed to determine the best fibrin
      sealant mixtures both to achieve hemostasis and to encourage healing. It may even
      be desirable to use different sealant formulations for particular clinical
      situations.

PMID- 9194886
TI  - Clinical problem of intraperitoneal postsurgical adhesion formation following
      general surgery and the use of adhesion prevention barriers.
AB  - Because of multiple studies demonstrating barrier efficacy, adhesion prevention
      adjuvants have received widespread acceptance in appropriate surgical settings.
      Many investigators are incorporating adhesion prevention barriers into their
      routine clinical practice and are achieving good results. Although both Seprafilm
      and Interceed barriers were shown to be safe and effective in all human clinical
      trials, their use did not eliminate adhesions in all patients. Efficacy of these
      barriers is limited to surgical situations in which the area in question can be
      completely covered. Physician acceptance is constrained by technical
      difficulties, including the need for hemostasis and removal of excess peritoneal
      fluid (Interceed), as well as limitations in application and handling properties
      within the surgical field (Seprafilm).

PMID- 9194887
TI  - Chronic wounds.
AB  - Skin ulcers are the most common chronic wounds. Current management principles and
      theories of causation of the most common ulcers--pressure, diabetic, and venous-
      are described. Issues related to occlusive dressings, compression dressings,
      topical antimicrobials, debridement, growth factors, grafting, and bioengineered
      tissue therapy are discussed. Special emphasis is placed on regulatory concerns.

PMID- 9194888
TI  - Hypertrophic scars, keloids, and contractures. The cellular and molecular basis
      for therapy.
AB  - Keloids, hypertrophic scars, and contractures are a result of aberrations of the
      normal wound healing process. An understanding of the cellular and molecular
      events that are implicated in the development of these fibroproliferative
      disorders will allow for optimization of wound healing. In turn, treatment
      choices can be based on the most current scientific information available.

PMID- 9194891
TI  - [78th German Congress of Radiology. Wiesbaden, 7-10 May 1997. Abstracts].

PMID- 9194889
TI  - The enhancement of wound healing with human skin allograft.
AB  - Although clean incisional wounds can be closed easily, contaminated wounds,
      wounds with tissue loss that cannot be closed primarily, and chronic wounds are
      generally not closed and suffer the effects of being open. It follows that wound
      healing would be enhanced if these wounds could be closed. This article describes
      how skin allograft biologic dressings are used to close such wounds temporarily
      to bestow the benefits of wound closure. It also describes the benefits of human
      skin allografts and the history and basic science related to their use. Reference
      is made to newer wound covers that have the potential to provide similar benefits
      to open wounds.

PMID- 9194892
TI  - A low expressor line of transgenic mice carrying a mutant human Cu,Zn superoxide
      dismutase (SOD1) gene develops pathological changes that most closely resemble
      those in human amyotrophic lateral sclerosis.
AB  - About 15-20% of patients with familial amyotrophic lateral sclerosis (ALS) carry
      one of several missense mutations in the gene for Cu,Zn superoxide dismutase
      (SOD1). We have previously reported on an animal model of this disease produced
      by the transgenic expression of a mutant form of human SOD1 containing a Gly93-
      >Ala amino acid substitution. Several lines of transgenic mice were produced,
      characterized by a differing tempo and severity of disease that generally
      correlated with the number of mutant gene copies that these lines expressed. We
      reported that mice expressing high copy numbers (18-25) developed a disease with
      a relatively short course and with a pathology mainly characterized by severe
      vacuolar degeneration of motor neurons and their process. Lewy-like bodies and
      swollen axons were also present. The exquisite localization to motor neurons was
      the feature that made the pathology in these overexpressors germane to the human
      disease. Severe vacuolar degeneration, however, was considered to be at variance
      with human ALS, in which similar changes have not been described. In the present
      study, we have made a temporal characterization of microscopic and
      immunohistochemical changes in a line of transgenic mice expressing lower copy
      numbers of the mutant gene. These mice, designated G5/G5, survive more than 400
      days and present pathological changes which are virtually identical to those in
      the human disease. In fact, in these animals, anterior horn cell depletion,
      atrophy, astrocytosis, and the presence of numerous ubiquitinated Lewy-like
      bodies and axonal swellings are the main pathological features, while vacuolar
      pathology is minimal. This study underscores the importance of the level of
      expression of the mutant enzyme in the resulting clinical and pathological
      disease, and supports the value of this transgenic model as an excellent tool for
      investigating both pathogenesis of human ALS and possible therapeutic avenues.

PMID- 9194893
TI  - Disordered migration and loss of virus-infected neuronal cells in developing
      mouse brains infected with murine cytomegalovirus.
AB  - Microcephaly is the most prominent symptom of the developmental brain
      abnormalities induced by congenital cytomegalovirus (CMV) infection. To
      investigate the effect of CMV infection on neuronal migration in developing
      brains, mouse embryos on one side of uteri received, on day 15.5 of gestation
      (E15.5), an injection of murine CMV (MCMV) into the cerebral ventricles, and the
      embryos on the other side of the uteri were injected with minimum essential
      medium (MEM). Labeling with 5-bromo-2-deoxyuridine (BrdU) was accomplished by
      intraperitoneal injection of BrdU 6 h later. Disturbance of the neuronal
      migration and loss of neurons were observed postnatally in the brains of MCMV
      infected mice, which were identified by immunohistochemical staining of viral
      antigen. Double staining of BrdU-labeled and viral antigen-positive cells in
      brains on the 7th postnatal day showed that the migration of BrdU-single-labeled
      cells, mainly localized in cerebral layers II-III, mostly preceded that of the
      viral antigen-positive cells. However, about 7.5% of the cells observed were
      double-labeled, especially in the layers III-IV, and a few double-stained cells
      were markedly disturbed in migration. In the brains of offspring labeled with
      BrdU 72 h after infection with MCMV on E15.5, most of the double-stained cells
      were seen around the ventricular and subventricular zones. These findings suggest
      that a disturbance of neuronal migration in addition to neuronal loss may play a
      crucial role in the development of microcephaly in congenital CMV infection in
      humans.

PMID- 9194894
TI  - Ultrastructural characterization of the tau-immunoreactive tubules in the
      oligodendroglial perikarya and their inner loop processes in progressive
      supranuclear palsy.
AB  - Coiled bodies and interfascicular threads are conspicuous white matter
      abnormalities of brains of patients with progressive supranuclear palsy (PSP).
      Both structures are argyrophilic and immunoreactive for the microtubule-binding
      protein tau. This report concerns the ultrastructural localization of
      interfascicular threads and their relationship to coiled bodies in five PSP
      patients. We showed for the first time that abnormal tubules with a 13- to 15-nm
      diameter and fuzzy outer contours were the common structures of coiled bodies in
      the oligodendroglial perikarya and of interfascicular threads. Moreover, the
      tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive
      tubules of interfascicular threads were located in the inner loop of the myelin
      sheath. Our study further indicated that the thread-like structures in the white
      matter comprised, at least in part, oligodendroglial processes, and that they
      were also present in gray matter. We consider that the formation of coiled bodies
      in the perikarya and of interfascicular threads represents a common cytoskeletal
      abnormality of the oligodendroglia of PSP patients. Moreover, even though the
      white matter alterations of PSP resemble those of corticobasal degeneration,
      there are certain ultrastructural differences in the abnormal oligodendroglial
      tubules of the two diseases.

PMID- 9194895
TI  - Demyelination in severe combined immunodeficient mice by intracisternal injection
      of cerebrospinal fluid cells from patients with multiple sclerosis:
      neuropathological investigation.
AB  - Demyelinating lesions have been observed in severe combined immunodeficient
      (SCID) mice after intracisternal administration of cerebrospinal fluid cells
      (CSFC) from patients with multiple sclerosis (MS). Further investigation in our
      laboratory revealed that CSFC from 6 to 15 patients at exacerbation of MS caused
      demyelination. The factor leading to demyelination appears to be the high
      frequency of relapses during a short period, but not to the severity of the
      disease. Neuropathological and immunohistochemical studies revealed that a lack
      of inflammatory mononuclear cell infiltration within and around the demyelinating
      lesions or in leptomeninges was a common characteristic in all SCID mice with
      CSFC-induced demyelination. In affected mice killed 2-3 weeks after
      intracisternal administration of CSFC, foamy/vacuolar lesions with a small or
      moderate number of lipid-laden macrophages were seen in the white matter.
      Ultrastructurally, relative preservation of axons, in contrast to myelinoclastic
      features, as well as some remyelinated axons were observed. In affected SCID mice
      killed 4-6 weeks after intracisternal administration, more widespread foamy
      macrophages and necrotic foci with poor remyelination were seen. The findings
      were similar to those seen in experimental allergic encephalomyelitis, though
      without lymphocytic infiltration, but were quite different from the lesions
      observed in Theiler's murine encephalitis virus infection. The absence of an
      immunohistochemical reaction to the human leukocyte common antigen in the
      infiltrating mononuclear cells suggested that the graft-versus-host reaction was
      unlikely cause of the demyelinating lesions.

PMID- 9194896
TI  - Ultrastructural concomitants of hypoxia-induced angiogenesis.
AB  - Prolong hypoxia results in structural and functional adaptive responses to
      improve tissue oxygen delivery. Structural changes within the brain include
      vascular proliferation and elongation. The aim of the current study was to
      investigate whether ultrastructural changes in capillary walls also occur as part
      of the adaptive response. Adult rats were exposed to 2 or 3 weeks of moderate
      hypobaric hypoxia at 0.5 atmospheres and their cerebral microvasculature examined
      using quantitative ultrastructural methods. We found that hypoxic rats had an 18%
      increase in their brain capillary diameter but no change in endothelial wall
      thickness, basement membrane thickness, or coverage of the endothelial wall by
      pericytes. The increased diameter of cerebral capillaries may plan an important
      role in decreasing the resistance to capillary perfusion which is brought about
      by the increased erythrocyte fraction in the blood of hypoxic rates.
      Ultrastructural features relevant to the blood-brain barrier were maintained in
      hypoxic rats. Pericytes, that are thought to form a second line of defense in the
      blood-brain barrier, maintained their numerical and size relationships to the
      endothelial cells. Endothelial junctions were unchanged and endothelial vesicles
      were somewhat lower in density than normal at 2 weeks of hypoxia, but had
      regained their normal density by 3 weeks. Mitochondria of the brain capillary
      endothelial cells maintained normal numerical and volume densities in hypoxia,
      but the mitochondria of the surrounding neuropil were decreased significantly by
      about 30%.

PMID- 9194897
TI  - The distribution and dynamic density of oligodendroglial cytoplasmic inclusions
      (GCIs) in multiple system atrophy: a correlation between the density of GCIs and
      the degree of involvement of striatonigral and olivopontocerebellar systems.
AB  - The distribution and dynamic density of oligodendroglial cytoplasmic inclusions
      (GCIs) were studied based on 30 cases of multiple system atrophy (MSA), including
      striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and Shy
      Drager syndrome. GCIs were widely spread throughout the central nervous system,
      including the striatonigral and olivopontocerebellar systems. Inclusion-bearing
      cells appeared to be oligodendrocytes which usually had larger and lighter nuclei
      than those of normal-looking oligodendrocytes. The distribution of GCIs was
      similar in all cases, irrespective of the degrees of OPCA and SND, but the
      frequency of GCIs varied from case to case. We classified all the cases into two
      categories based on the degree of neuropathological changes of SND (mild and
      severe) and, independently, into three groups based on that of OPCA (minimal,
      moderate and severe), i.e., a total of six groups. An association between the
      frequency of GCIs and the severity of the lesions was obtained. For example, many
      GCIs were seen the cerebellar white matter in the cases in which OPCA was not
      histologically confirmed. More GCIs were seen in the cases with moderate OPCA. In
      the cases with severe OPCA, GCIs were rarer and smaller, in proportion to the
      devastation of fibers; no GCIs were seen in the cases with more severe OPCA. The
      incidence of GCIs showed a positive correlation to the severity of OPCA but not
      that of SND in the corticopontine tracts, of both OPCA and SND in the pyramidal
      tracts, and of SND but not of OPCA in the pencil fibers of the putamen. It is
      suggested that GCIs may represent either a change synchronous with neuronal
      degeneration or a phenomenon preceding neuronal changes, especially in the
      cerebellar white matter. Thus, they may represent the early changes in MSA and
      may be a useful neuropathological hallmark for diagnosis of MSA, even in cases
      with minimal OPCA and SND.

PMID- 9194898
TI  - Increase in oxidative key enzymes in a case of muscle ubiquinol-cytochrome c
      reductase deficiency.
AB  - In a 29-year-old patient suffering from exertional muscle intolerance with a
      ubiquinol-cytochrome c reductase deficiency related to a cytochrome b gene point
      mutation of the mitochondrial DNA, we conducted a study of the aims of which
      were: (1) to test whether changes in the maximum activities of muscle key enzymes
      of the main energy-producing pathways occur, (2) to address the issue of whether
      fibers of different types are equally affected in their enzymatic machinery
      involved in energy production, and (3) to correlate the results obtained with
      histochemical and 31P NMR spectroscopy data. When compared to results obtained in
      six normal subjects, our study clearly shows that the type I fibers of the
      patient virtually all contained subsarcolemmal mitochondrial aggregates and
      increased activities of succinate dehydrogenase and cytochrome c oxidase;
      microdissected type I fibers also displayed a significant increase in both
      citrate synthase and beta-hydroxyacyl-CoA dehydrogenase, two key enzymes of
      mitochondrial oxidative metabolism. Despite these changes in the patient's
      muscle, its whole energy-producing machinery remained impaired as revealed by a
      slowed post-exercise recovery of phosphocreatine.

PMID- 9194899
TI  - p53 accumulation and apoptosis in embolized meningiomas.
AB  - Preoperative embolization of meningiomas is performed to decrease blood loss at
      surgery. While it is also expected to reduce tumor recurrence by producing
      necrosis at the site of dural attachment, very little has been described about
      what happens to the non-necrotic tumor cells. We investigated how the
      proliferative activities of meningiomas were modified after embolization. In nine
      meningiomas which were embolized preoperatively, proliferative potentials and
      expression of cell cycle inhibitors were assessed immunohistochemically using MIB
      1, anti-53 (DO-1 and DO-7), and anti-p21 (WAF1/CIP1) monoclonal antibodies. To
      determine whether a cell underwent apoptotic death besides necrosis, we applied
      the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end
      labeling method. Results were compared with control meningiomas without
      embolization. MIB-1 positive cells often gathered in perinecrotic areas, although
      the mean MIB-1 staining index of the embolized meningiomas was not significantly
      different from the control. p53 and its downstream effector p21 accumulated
      mainly in the perinecrotic areas in eight of the nine embolized meningiomas.
      Apoptosis was also observed in the concomitant areas. Double staining for both
      MIB-1 and p21 frequently showed positive cells for both antibodies. The
      accumulation of MIB-1 positive cells in the embolized meningiomas may not be a
      sign of fast growth or malignancy, but it may implicate arrest of cell cycle by
      the p21. This study indicates that embolized meningiomas exhibit not only
      necrosis but also apoptosis and cell cycle arrest. The latter effects appear to
      be at least partly p53 dependent.

PMID- 9194900
TI  - Neuronal loss and gliosis of the amygdaloid nucleus in temporal lobe epilepsy. A
      quantitative analysis of 70 surgical specimens.
AB  - Although clinical and electrophysiological evidence indicates that the amygdaloid
      body plays an important role in the pathogenesis of temporal lobe epilepsy, there
      are very few detailed data on histopathological changes in this nucleus in
      epilepsy patients. In the present study we have examined the lateral nucleus of
      the amygdaloid body in 70 surgical specimens from patients with temporal lobe
      epilepsy and in 10 control specimens with respect to neuronal density and
      gliosis. The results were compared to the neuronal loss in the hippocampal
      formation. Our goal was to examine the pathological alterations of the amygdaloid
      body and their correlation with other morphological changes in temporal lobe
      epilepsy. In epilepsy patients with Ammon's horn sclerosis or focal lesions of
      the temporal lobe, the neuronal density of the lateral amygdaloid nucleus was
      significantly decreased as compared to normal controls (P < 0.001). Overall, the
      mean volumetric density in epilepsy patients was reduced to 59% of that in normal
      individuals. There was no correlation between the neuronal density in the lateral
      amygdaloid nucleus and that in the different segments of the hippocampal
      formation or to the age at onset or the duration of epilepsy. The neuronal loss
      of the amygdaloid nucleus correlated well with the presence of fibrillary
      gliosis. Our findings demonstrate that the amygdaloid body is severely altered in
      most patients with temporal lobe epilepsy and that these changes are independent
      of those in the hippocampus. The presence of neuronal loss and gliosis in the
      amygdaloid nucleus of patients with focal lesions but no Ammon's horn sclerosis
      is compatible with an involvement of the amygdala in secondary epileptogenesis.

PMID- 9194901
TI  - Schwann cell changes induced as early as one week after galactose intoxication.
AB  - In galactose neuropathy, aldose reductase inhibitor (ARI)-preventable Schwann
      cell injury has been reported in studies in which galactose feeding continued
      over a period of months. Given the link between these morphologic changes and
      polyol pathway flux, polyol accumulation after just days of galactose feeding
      points to the possibility that structural changes occur much earlier than
      previously reported. The aim of this study was to examine rat sciatic nerve after
      7 days of galactose feeding for evidence of myelinated fiber injury and establish
      whether it is related to polyol accumulation. Compared to control or ARI-treated
      galactose-fed rats, nerves from untreated galactose-fed rats had increased water
      (P < 0.05) ad dulcitol (P < 0.008) content and decreased amounts of myo-inositol
      (P < 0.01). Electron microscopy revealed reactive Schwann cell changes in
      myelinated fibers characterized by increased cytoplasmic volume, and the
      occurrence of lipid droplets pi granules of Reich and enlarged mitochondria.
      Dystrophic accumulation of intermediate filaments was also observed in the inner
      glial loop. Degenerative changes included periaxonal swelling, enlarged
      mitochondria without recognizable cristae, lysis of Schwann cell cytoplasm and
      demyelination. Reactive (P < 0.05) and degenerative (P < 0.01) changes as well as
      the number of redundant basal lamina profiles (P < 0.05) were significantly more
      frequent in untreated galactose-fed rats compared to controls. ARI treatment
      attenuated these changes. Consistent with the initial stages of onion-bulb
      formation, profiles with imbricate Schwann cells were also seen only in untreated
      galactose-fed rats. The findings suggest that short-term increases in polyol
      pathway activity can have deleterious effects Schwann cells of myelinated fibers.

PMID- 9194902
TI  - Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental
      maturity.
AB  - Cortical dysplasias (CD) are characterized histologically by disorganized
      cortical lamination and abnormally shaped neurons. We hypothesized that neurons
      within CD have failed to differentiate fully and may express proteins such as
      cytoskeletal elements characteristic of immature cells. Disrupted expression of
      certain cytoskeletal proteins, which have been implicated in neuronal polarity,
      process outgrowth, and migration, could result in disorganized cortical
      lamination. Thus, we probed two CD subtypes, focal CD (FCD) and
      hemimegalencephaly (HME), with antibodies specific for cytoskeletal proteins that
      are developmentally regulated in neural progenitor cells and neurons to define
      more fully the developmental phenotype of neurons within CD. Microtubule
      associated protein 1B (MAP1B) and the intermediate filament (IF) protein nestin
      are enriched in neural progenitors, whereas MAP2B, phosphorylated and non
      phosphorylated forms of medium (NFM) and high (NFH) molecular weight
      neurofilament (NF) proteins, as well as the light NF subunit (NFL) and IF protein
      alpha internexin are expressed in developing and mature neurons. Immunolabeling
      for internexin and MAP1B was more abundant in the most abnormally shaped neurons
      that populated dysplastic regions than in adjacent regions exhibiting milder
      cytoarchitectural abnormalities or control cortex. Nestin immunoreactivity was
      noted in large dysplastic and heterotopic neurons within the deeper cortical
      layers of CD specimens but not in normal cortex. In contrast, neurons in CD
      specimens also expressed cytoskeletal markers characteristic of differentiated
      neurons such as NF subunits and MAP2B. These findings suggest that the
      cytoarchitectural abnormalities in CD may reflect pathophysiological changes in
      the developing brain that disrupt expression of several key components of the
      neuronal cytoskeleton and may contribute to impaired migration of cortical
      neurons.

PMID- 9194903
TI  - Accumulation of mitochondrial ATP synthase subunit c in muscle in a patient with
      neuronal ceroid lipofuscinosis (late infantile form).
AB  - We report a case late infantile neuronal ceroid lipofuscinosis (NCL). Abnormal
      granules were found in the skeletal muscle fibers, Schwann cells, perineurial
      cells, endothelial cells, fibroblasts, and perivascular smooth muscle cells in
      the sural nerve. Electron microscopy revealed that these granules showed
      fingerprint profiles, curvilinear profiles or membrane-bound membranous
      structures. Acid phosphatase reaction was increased in these cells.
      Immunohistochemical studies for mitochondrial ATP synthase subunit c showed a
      strong reaction in these cells, suggesting abnormal accumulation of subunit c.
      Immunohistochemistry for subunit c in muscle may be useful in the diagnosis of
      late infantile NCL.

PMID- 9194904
TI  - Friedreich's ataxia with isolated vitamin E deficiency: a neuropathological study
      of a Tunisian patient.
AB  - The neuropathological findings in a Tunisian patient with Friedreich's ataxia
      with vitamin E deficiency are reported. The main histological changes are: (1)
      spinal sensory system demyelination with neuronal atrophy, axonal spheroids and
      corpora amylacea; (2) neuronal lipofuscin accumulation in the third cortical
      layer of the cerebral cortex, thalamus, lateral geniculate body, twelfth and
      ambiguus nuclei, spinal horns and posterior root ganglia. Ultrastructurally, the
      lipopigments were of uniform granularity without lipid droplets.

PMID- 9194905
TI  - Signet-ring cell oligodendroglioma--report of two cases and discussion of the
      differential diagnosis.
AB  - Two cases of oligodendroglioma consisting largely of signet-ring cells were
      analyzed histopathologically, immunohistochemically and at the ultrastructural
      level. The signet-ring cells were negative for a panel of tumor lineage markers
      including glial fibrillary acidic protein, and were negative for Ki-67 (MIB-1
      immunohistochemistry). In contrast with the abundance of lysosomal structures
      reportedly present in the so-called eosinophilic granular cells in
      oligodendrogliomas, degenerating mitochondria were mainly seen in the cytoplasm
      of the signet-ring cells. The differential diagnosis of the oligodendroglial
      signet-ring cell tumors occurring in children and in adults is discussed.

PMID- 9194906
TI  - No electrocortical evidence of automatic mismatch dysfunction in children of
      alcoholics.
AB  - The mismatch negativity (MMN) event-related potential (ERP) component is an
      automatic, attention-independent brain response to auditory stimulus change,
      which has been reported to be smaller in alcoholics relative to nonalcoholic
      controls. To determine whether MMN decrements might be a trait marker of
      alcoholism that is also present in nonalcoholic individuals at high risk for
      developing alcoholism, we investigated MMN in 9- to 18-year-old children of
      alcoholics (n = 20) and control children (n = 20) in three different stimulus
      conditions using a passive auditory oddball paradigm. There were no statistically
      significant between-group differences observed in amplitude, scalp topography,
      and peak latency of MMN. These findings, if replicated, suggest that reported MMN
      decrements in alcoholics most likely represent a state marker, and not a trait
      marker, of alcoholism. Also, inasmuch as another ERP component, the P300, is
      attention-dependent and reported to be smaller in children of alcoholics, the
      present results implicate that deviations in attentive, but not in automatic,
      information processing are associated with alcoholism vulnerability.

PMID- 9194907
TI  - A transketolase assembly defect in a Wernicke-Korsakoff syndrome patient.
AB  - Thiamine deficiency, a frequent complication of alcoholism, contributes
      significantly to the development of damage in various organ systems, including
      the brain. The molecular mechanisms that underlie the differential
      vulnerabilities to thiamine deficiency of tissue and cell types and among
      individuals are not understood. Investigations into these mechanisms have
      examined potential variations in thiamine utilizing enzymes. Transketolase is a
      homodimeric enzyme containing two molecules of noncovalently bound thiamine
      pyrophosphate. In the present study, we examined a his-tagged human transketolase
      that was produced in and purified from Escherichia coli cells. Previous findings
      demonstrated that purified his-transketolase had a Km app for cofactor and a
      thiamine pyrophosphate-dependent lag period for attaining steady-state kinetics
      that was similar to transketolase purified from human tissues. Interestingly, the
      time of the lag period, which is normally independent of enzyme concentration,
      was found herein to be dependent on the concentration of the recombinant protein.
      This atypical behavior was due to production in E. coli. Generation of the
      normal, enzyme concentration-independent state required a cytosolic factor(s)
      derived from human cells. Importantly, the required factor(s) was found to be
      defective in a Wernicke-Korsakoff patient whose cells in culture show an enhanced
      sensitivity to thiamine deficiency.

PMID- 9194908
TI  - Infants' suckling responses to the flavor of alcohol in mothers' milk.
AB  - Contrary to medical folklore, previous research has demonstrated that alcohol
      consumption by lactating women diminished milk intake by their infants during
      breast feeding. To determine whether this decrease in milk consumption was due to
      the infants responding to the altered flavor of the milk that also resulted, we
      evaluated the infants' intake and sucking responses to alcohol-flavored human
      milk outside of the context of breast feeding, thereby separating the changes due
      to the infants response to the flavor from any other changes that could also
      result from acute maternal alcohol consumption such as alterations in milk
      ejection or the composition of milk. The testing procedure consisted of a two
      bottle preference test that was composed of four, 60-sec trials in which the
      mother's milk flavored with alcohol was alternated with the mother's milk alone
      in an ABBA or BAAB design. Attached to the nipple of each bottle was a transducer
      that responded to pressure changes produced by the infants' suckling. There was
      no suppression of sucking or intake in response to the ethanol-flavored milk.
      Rather, the infants consumed significantly more and sucked more frequently when
      drinking the alcohol-flavored milk compared with the unaltered milk. That
      experience with the flavor of alcohol in mothers' milk modified the infants'
      responses to alcohol flavor is suggested by the relationship between the reported
      frequency of mothers' drinking during lactation and the infants' rhythm and
      frequency of sucking when feeding the alcohol-flavored milk. These findings
      indicate that infants can readily detect the flavor of alcohol in mother's milk
      but that the decrease in consumption at the breast after maternal alcohol
      consumption is apparently not due to the infants rejecting the flavor of alcohol
      in their mothers' milk.

PMID- 9194909
TI  - Comparison of the Alcohol Dependence Scale and diagnostic interview schedule in
      homeless women.
AB  - The Alcohol Dependence Scale (ADS) is a 25 item self-report instrument designed
      to evaluate the degree of severity of alcohol dependence. Although previous
      studies have reported on the validity of the ADS, no studies using the ADS have
      been done on the homeless population, a special and rapidly growing population.
      To assess the utility of the ADS in a population of homeless, substance-abusing
      women, the ADS questionnaire was compared with the DSM-III-R alcohol use disorder
      diagnosis as measured by the Diagnostic Interview Schedule (DIS). Both the ADS
      and the DIS were administered to 149 homeless, substance-abusing women by
      trained, lay interviewers. There was good agreement between the ADS and the past
      year DIS diagnosis of alcohol use disorder. The level of agreement between the
      ADS and DIS, as well as sensitivity and specificity, for various ADS cutoff
      scores are reported to facilitate selection of cutoff scores by clinicians and
      future researchers.

PMID- 9194910
TI  - Polymorphism of alcohol-metabolizing genes affects drinking behavior and
      alcoholic liver disease in Japanese men.
AB  - Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2
      (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-450IIEI. The
      purpose of this study was to clarify the role of polymorphism of these ethanol
      metabolizing enzymes in drinking behavior and the progression of alcoholic liver
      disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45IIEI genes
      were determined by polymerase chain reaction, followed by restriction fragment
      length polymorphism analysis in 189 normal Japanese men and 26 male patients with
      alcoholic liver disease. Drinking behavior was estimated by self-assessment
      according to DSM-III-R criteria. Facial flushing was reported in 91 subjects
      heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but
      was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism
      of ADH2 and P-450IIEI did not differ between flushers and nonflushers. Although
      the flushers only drank a small amount of alcohol (< 20 g of ethanol/day), the
      nonflushers were divided into a group of moderate drinkers (20 to 80 g/day; n =
      54) and a group of heavy drinkers (> 80 g/day; n = 42). A high preponderance of
      heterozygosity for the ADH2*1/*2 genes (20/42; 60%) and a high frequency of the
      ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers.
      However, cytochrome P-45IIEI gene polymorphism was similar among the moderate and
      heavy drinkers. Not only a high frequency of the ALDH2*1 and ADH2*1 alleles, but
      also a high frequency of the P-450IIEI c2 allele was found in the patients with
      alcoholic liver disease. From these results, the drinking behavior of Japanese
      men is strongly influenced by the ALDH2*1 allele, and the level of alcohol intake
      is affected by the ADH2*1 allele, but not by cytochrome P-45IIEI. However,
      progression to alcoholic liver disease among heavy drinkers may be affected by
      the cytochrome P-450IIEI c2 allele.

PMID- 9194911
TI  - The distribution of fatty acid ethyl esters among lipoproteins and albumin in
      human serum.
AB  - Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism
      and have been implicated as mediators of ethanol-induced organ damage. Previous
      studies have demonstrated that FAEEs bind to lipoproteins and albumin in human
      plasma after ethanol ingestion. Analysis of human serum with varying blood
      ethanol levels and endogenously formed FAEEs revealed a positive correlation
      between serum FAEE concentration and the percentage of FAEEs associated with
      lipoproteins, predominantly very low density and low density lipoprotein. Similar
      results were obtained when increasing amounts of FAEEs were added to serum with
      zero blood ethanol. Additional studies indicated that free fatty acids and FAEEs
      do not compete for binding to albumin or lipoproteins. Data support the
      conclusion that the distribution of FAEEs among their carriers in the serum is
      dependent on serum FAEE concentration.

PMID- 9194912
TI  - Effect of apolipoprotein E phenotype on plasma lipids and lipoproteins in alcohol
      abusers.
AB  - The effect of apolipoprotein (apo) E phenotype on the concentration and chemical
      composition of plasma lipoproteins was studied in 73 male alcohol abusers and 50
      male controls. The apo E phenotype was confirmed by genotyping to avoid possible
      effects of posttranslational modifications by alcohol or its metabolites. The
      lipid and protein concentrations of both intermediate density lipoprotein and low
      density lipoprotein were lower among the alcohol abusers than among the controls,
      those with E4 having the highest low density lipoprotein masses in both groups.
      In the alcohol abusers with E4 only the high density lipoprotein (HDL)-2 lipid
      and protein concentrations were higher than in the controls with respective
      phenotype group, whereas both HDL2 and HDL3 were higher in alcohol abusers with
      other apo E phenotypes, suggesting that apo E modulates the alcohol-effect on HDL
      subfractions. This effect was not explained by cholesteryl ester transfer protein
      activity, which was lower in the alcohol abusers (25 to 34%, p < 0.01), but
      without significant difference between the apo E groups. In conclusion, alcohol
      abuse does not cause major changes in the electric charge of apo E in humans.
      Heavy alcohol intake seems to have a beneficial effect on plasma lipids and
      lipoproteins, regardless of the apo E phenotype, but the modulation of the
      alcohol-induced increase in HDL by apo E phenotype should be taken into
      consideration in future studies.

PMID- 9194913
TI  - A review of research on the Alcohol Use Disorders Identification Test (AUDIT).
AB  - Research on the core version of the Alcohol Use Disorders Identification Test
      (AUDIT) is reviewed. Sensitivities and specificities of the AUDIT or criteria of
      current hazardous use and, to a slightly lesser extent, lifetime alcohol
      dependence are high. In general, AUDIT scores are at least moderately related to
      other self-report alcohol screening tests. Several studies also show them as
      correlated with biochemical measures of drinking. Results of the AUDIT have also
      been associated with more distal indicators of problematic drinking. Indices of
      internal consistency, including Cronbach's alpha and item-total correlations, are
      generally in the 0.80's. Future directions for research on the AUDIT are
      suggested.

PMID- 9194914
TI  - Psychiatric referrals associated with substance use disorders: prevalence and
      gender differences. European Consultation-Liaison Workgroup.
AB  - A psychoactive substance use disorder (ICD-10) was diagnosed in 28% of 1222
      psychiatric referrals in six general hospitals in Finland. In the age group 35 o
      50 years, 53% of men and 29% of women had a substance use disorder. In the age
      group 35 to 50 years, sociodemographic characteristics differentiated men
      diagnosed with substance use disorders from other male consultation patients, but
      women with substance use disorders were similar to other female consultation
      patients. Urgency (i.e., consultation required within the same day) was
      accentuated in referrals associated with substance use disorders. Of attempted
      suicides, 65% were related to substance use disorders. Use of sedatives or
      hypnotics had more frequently induced disorders in women with substance use
      diagnosis compared to men with diagnosis (30% vs. 13%; p < 0.01). Female
      consultation patients with substance use disorders more often than respective
      male patients were current mental health outpatients. In conclusion, the
      proportion of substance use disorders among psychiatric consultation patients was
      remarkably higher in the present study (28%) compared with the average provided
      by the earlier literature (12%), and therefore, at least in Finland, psychiatric
      assessment of general hospital patients should always include assessment for the
      presence of substance use disorders. If substance use is only looked for in
      patients who have social problems typical of advanced misuse, detecting female
      substance use might be impeded. Relation of attempted suicides to substance use
      disorders was confirmed. To prevent misuse of prescribed drugs detected
      particularly in female consultation patients, and to prevent attempted suicides,
      doctors' attention is called to prescriptions of sedatives and hypnotics.

PMID- 9194915
TI  - The effect of anonymous vs. nonanonymous rating conditions on patient
      satisfaction and motivation ratings in a population of substance abuse patients.
AB  - Patient self-report in evaluations involving alcohol and other drug abuse has
      generally been found to be reliable and valid. However, little is known about the
      variables associated with greater or lesser degrees of reliability and validity.
      This study was conducted to determine how motivation and satisfaction ratings
      obtained under anonymous conditions would compare with ratings obtained under
      nonanonymous conditions. Over the course of 12 months, 1397 subjects in the
      Boston Target Cities Project were assigned to either confidential or fully
      anonymous data collection procedures in an interrupted time-series design.
      Anonymity had either no effect on ratings or accounted for < 1% of the variance.
      Satisfaction and motivation ratings obtained under confidential conditions are
      probably as reliable and valid as ratings obtained under fully anonymous
      conditions.

PMID- 9194916
TI  - Effects of 5,7-dihydroxytryptamine lesions of the prefrontal cortex on
      consumption of sucrose-ethanol solutions: relationship to prefrontal monoamines.
AB  - Thirty adult male Wistar rats received 8 micrograms bilaterally of 5,7
      dihydroxytryptamine into the medial prefrontal cortex (mPFC). Rats were then
      trained, via a sucrose, fading paradigm, to consume increasing concentrations of
      alcohol. After death, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and
      their metabolites were measured in the mPFC, nucleus accumbens (NA), and raphe
      nucleus. The lesioned group demonstrated a reduction in 5-hydroxyindoleacetic
      acid (5-HIAA), DA, and NE in the mPFC (p < 0.05), and a trend toward reduction of
      5-HT in the NA. In comparison with controls, lesioned animals consumed less of
      all solutions containing sucrose and alcohol. On regression analyses, monoamines
      in the mPFC (i.e., 5-HIAA, dihydrophenylacetic acid and NE) predicted consumption
      of the 5% ethanol solution (p = 0.009), 10% ethanol solution (p = 0.0006), and
      the 5% sucrose solutions (p = 0.0006), but not the 20% sucrose solutions. In each
      case, monoamine levels were positively correlated with consumption. No
      relationships were seen between monoamine levels in the NA and raphe, and in
      consummatory behavior.

PMID- 9194917
TI  - Naltrexone treatment increases the aversiveness of alcohol for outbred rats.
AB  - Acute naltrexone treatments (0.0, 0.5, 1., or 3.0 mg/kg body weight) were
      administered to separate groups of rats and alcohol taste reactivity and
      consumption were measured. Rats were given daily naltrexone injections and then
      tested for taste reactivity to 10% alcohol 30 and 60 min after injection. Each
      reactivity trial (total of 4) was 60 sec during which 1 ml of fluid was infused.
      The rats' orofacial and body movements were videotaped and scored later. In the
      final measure, rats were placed on a restricted fluid access schedule and given
      naltrexone treatments 10 min before being presented with the 10% alcohol solution
      in the home case (60-min drinking period). After 4 days of consumption tests
      under the drug condition, the rats were given 4 more daily tests without the
      drug. Results indicated that the two highest naltrexone doses significantly
      decreased ingestive responding and increased aversive responding, particularly at
      the 30-min test. Both the 1.0 and 3.0 mg/kg body weight doses also significantly
      decreased alcohol consumption as measured during the free access tests. Alcohol
      consumption returned to control levels immediately after the drug treatments were
      stopped. The data show that dosages of naltrexone 1.0 mg or higher significantly
      alter both alcohol taste reactivity (increased aversiveness and decreased
      palatability) and alcohol consumption (decreased intake) in outbred rats. These
      results are discussed in relation to naltrexone treatment as a means for
      decreasing alcohol use and abuse.

PMID- 9194918
TI  - Free radical formation in livers of rats treated acutely and chronically with
      alcohol.
AB  - The spin trapping method was used to assess formation of free radical
      intermediates in vivo before and after acute alcohol administration to rats.
      Ascorbyl radicals and spin adducts of dietary alcohol or endogenous compounds,
      such as lipids, were detected with higher frequency in bile from alcohol-fed rats
      than in corresponding samples from rats fed control diets. When alcohol was given
      acutely to these animals, the 1-hydroxyethyl radical metabolite of ethanol was
      also formed at higher rates in livers of rats that had been fed ethanol
      chronically. Furthermore, formation of lipid radicals was enhanced after acute
      alcohol administration. These data support the hypothesis that chronic alcohol
      administration causes development of oxidative conditions in the liver, which
      subsequently lead to formation of differing types of radicals. Liver microsomes
      from alcohol-fed rats also metabolized ethanol to the 1-hydroxyethyl radical at
      higher rates than controls.

PMID- 9194920
TI  - Decreased measures of experimental anxiety in rats bred for high alcohol
      preference.
AB  - A prevalent notion holds that acute anti-anxiety actions of ethanol are important
      for the reinforcing properties of this drug, and might predispose individuals
      with pre-existing anxiety disorders for developing ethanol dependence. This
      notion remains controversial, and human studies have yielded conflicting results.
      Ethanol dependence is likely a heterogenous disorder, and the discrepancies might
      be explained by a different relationship between anxiety and alcohol
      reinforcement in different subtypes of alcoholism. Recent results in experimental
      animals suggest that antianxiety actions of ethanol are important reinforcers of
      voluntary ethanol consumption in heterogeneous rats. Here, we examined whether
      the relationship is different in the AA line of rats bred for high voluntary
      ethanol intake. Behavior was studied in two established animal models of anxiety,
      a punished drinking conflict test, and the elevated plus maze. In the conflict
      test, the AA line displayed a markedly disinhibited behavior over a range of
      shock intensities, compared both with their counterpart, the ANA line, and with
      regular Wistar rats. On the plus maze, both AA and Wistar rats showed lower
      measures of experimental anxiety than ANA subjects. The phenotype of the animals
      was confirmed using a two-bottle free choice alcohol drinking procedure. The
      disinhibited behavior and spontaneous ethanol preference of the AA line differs
      from what has been found in heterogeneous rats, and displays similarities to
      genetically transmitted type II alcoholism according to the nomenclature of
      Cloninger.

PMID- 9194919
TI  - Ethanol modulation of GABA-activated current responses in acutely dissociated
      retinal bipolar cells and ganglion cells.
AB  - This study examined the effect of acute ethanol exposure on GABA-activated whole
      cell current responses elicited in bipolar cells and ganglion cells of the rat
      retina. Acute exposure to ethanol potentiated GABA responses in 86% of the
      bipolar cells and in 52% of the ganglion cells tested. As determined in bipolar
      cells, ethanol was maximally effective at a concentration of 50 mM. In bipolar
      cells, a GABAC receptor-mediated component of the whole-cell response to GABA
      could be uncovered which was also potentiated by ethanol. However, ethanol was
      ineffective in enhancing bipolar cell responses to glycine. GABA-activated
      current responses monitored in ganglion cells that were insensitive to modulation
      by ethanol were sensitive to potentiation by diazepam. At higher concentrations
      (100-175 mM), ethanol by itself occasionally induced a chloride-mediated current
      but this occurred independent of an ethanol-induced potentiation of GABA
      responses. These data establish that ethanol can modulate the sensitivity of
      retinal neurons to GABA. Overall, the results presented in this study set the
      stage for future studies to examine the cellular and molecular bases for a
      differential neuronal sensitivity to an ethanol-induced modulation of GABA
      responses.

PMID- 9194921
TI  - Effect of exogenous GM1 on ethanol sensitivity in selectively bred mouse lines.
AB  - Ethanol sensitive long-sleep (LS) and ethanol resistant short-sleep (SS) mice are
      lines that have been genetically selected for differential central nervous system
      sensitivities to the hypnotic effect of ethanol. Because they were genetically
      selected only for differences in sensitivity to ethanol hypnosis, biochemical and
      physiological differences between them are likely related to their differential
      ethanol sensitivity. The synaptosomal and whole brain concentration of GM1
      ganglioside was previously shown to differ significantly between the lines.
      Further, GM1 alters membrane responses to ethanol, including a differential
      effect on LS and SS synaptosomal membrane disordering. Therefore, GM1 was
      administered intracerebroventricularly (i.c.v.) with micro-osmotic pumps, to
      partially bypass the blood-brain barrier and to test its effect on CNS
      sensitivity to ethanol hypnosis in LS and SS mice. In the first experiment, 3
      days' infusion of GM1 (20 micrograms/microliters, 24 microliters/day), saline
      control and treated LS and SS mice were tested for both regaining of the righting
      reflex and waking brain ethanol concentration. Incorporation of 3H-GM1 into brain
      membranes was verified by scintillation spectroscopy. GM1 did not alter ethanol
      sensitivity or brain ethanol concentration at time of waking in LS mice.
      Conversely, SS mice treated with GM1 were significantly more sensitive to ethanol
      hypnosis than saline controls as measured by the time to regain the righting
      reflex ("sleep time") and waking brain ethanol concentrations. In the second
      experiment, GM1-treated SS mice were again significantly more sensitive to
      ethanol hypnosis than saline controls. GM1 incorporation into the contralateral
      and ipsilateral cerebral hemispheres was determined by high-performance liquid
      chromatography.

PMID- 9194922
TI  - Behavioral sensitivity and ethanol potentiation of the N-methyl-D-aspartate
      receptor antagonist MK-801 in a rat line selected for high ethanol sensitivity.
AB  - The role of the N-methyl-D-aspartate (NMDA) receptors in differential ethanol
      sensitivity of the alcohol-insensitive [alcohol-tolerant (AT)] and alcohol
      sensitive [alcohol-nontolerant (ANT)] rat lines selected for low and high
      sensitivity to ethanol-induced (2 g/kg) motor impairment was studied in
      behavioral and neurochemical experiments. A noncompetitive antagonist of the NMDA
      receptor, dizocilpine maleate (MK-801; 0.2 mg/kg), impaired motor function in ANT
      rats, but not in AT rats, in a tilting plane test. The impairment was further
      potentiated by a dose (0.75 g/kg) of ethanol, which alone was inactive. This
      effect was apparently not associated with the locomotor stimulation produced by
      MK-801 (0.1 and 0.2 mg/kg), because stimulation did not differ between the rat
      lines. Locomotor stimulation was potentiated by the low ethanol dose in both rat
      lines. Ethanol treatment decreased the cerebellar and hippocampal cGMP
      concentrations both with and without MK-801 pretreatment in both rat lines. In
      situ hybridization using oligonucleotide probes specific for NMDA receptor
      subunit mRNAs NR1 and NR2A, B, C, and D revealed no clear differences in brain
      regional expression between ANT and AT rates. These results indicate that the
      alcohol-sensitive ANT rats are very sensitive to a low dose of ethanol in the
      presence of NMDA receptor antagonism, consistent with the hypothesis that this
      receptor system is involved in acute ethanol intoxication.

PMID- 9194923
TI  - Abnormalities of peripheral blood T lymphocytes and natural killer cells in
      alcoholic hepatitis persist after a 3-month withdrawal period.
AB  - Present information about the behavior of the different lymphoid subsets in
      alcoholic hepatitis (AH), including cells displaying cytotoxic activity, is
      scanty and contradictory. The aim of this study was to gain further insight into
      knowledge of the immunological abnormalities involved in AH and the possible role
      of ethanol (EtOH) consumption in these changes. We analyzed the distribution of a
      wide range of peripheral blood (PB) lymphoid subsets, both during active EtOH
      intake and after a 3-month withdrawal period, using multiple stainings with
      monoclonal antibodies and flow cytometry, as well as natural killer (NK)
      cytotoxic activity. AH patients entering the study were selected strictly; only
      those undergoing their first episode of AH with no other lesions at liver biopsy
      were enrolled. Regarding the alcohol intake period, the most striking finding was
      a significant increase of the absolute number of PB T cells affecting both CD4+
      and CD8+ lymphocytes. These changes were associated with a higher expression of T
      cell activation antigens, such as HLA DR and CD11c. Simultaneously, a significant
      increase in both NK cells (CD3-/CD56+) and the cytotoxic T cells coexpressing the
      CD3 and the CD56 molecules together with an increased NK cytotoxic activity were
      observed. By contrast, the CD19+/CD5+ B-cell subset was significantly decreased.
      No significant changes were observed with EtOH withdrawal except in CD5+ B
      lymphocytes, which returned to normal values. Our results show that, in AH
      patients, a significant expansion of both activated T cells and NK lymphocytes
      occurs in the PB, which is associated with an increased NK cytotoxic activity.
      Interestingly these abnormalities persist during the withdrawal period.

PMID- 9194924
TI  - Naltrexone blocks acquisition of voluntary ethanol intake in rats.
AB  - The effects of naltrexone (NTX) on the acquisition of ethanol drinking was
      assessed in rats. NTX (0, 2.5, 5.0, or 10.0 mg/kg) was administered to rats
      presented with an ascending series of ethanol concentrations (2%, 4%, 6%, and 8%
      v/v) and water. The 2.5 and 10 mg/kg doses of NTX attenuated the acquisition of
      voluntary drinking of 8% ethanol, but the 5.0 mg/kg dose of NTX had no effect on
      ethanol intake. The acquisition paradigm was repeated in experiment 2 with naive
      animals that received 0, 5.0, or 7.5 mg/kg of NTX. Neither dose of NTX affected
      ethanol intake, preference for alcohol, or water intake. Total fluid intake was
      suppressed in the NTX groups, but only on the second presentations of the 2% and
      6% concentrations of ethanol. We suggest that the 2.5 and 10 mg/kg doses of NTX
      may have attenuated the acquisition of ethanol drinking by at least two different
      behavioral mechanisms.

PMID- 9194926
TI  - Naltrexone effects on ethanol drinking acquisition and on established ethanol
      consumption in C57BL/6J mice.
AB  - Naltrexone's success as a treatment agent for alcoholism seems to be due to its
      ability to reduce craving in abstinent, dependent individuals and to reduce the
      pleasure associated with subsequent intake. However, more study is needed to
      establish the optimal amount of time that naltrexone treatment should be
      continued. Little information seems to have been collected regarding the most
      effective dosing regimen for reducing alcohol craving and consumption, and the
      usefulness of opiate antagonists in the prevention of alcohol dependence in
      nonaddicts, rather than just as a treatment agent in addicted individuals, also
      deserves further study. The alcohol-preferring C57BL/6J (B6) mice were used to:
      (1) study naltrexone effects on consumption in established drinkers using an
      increasing dosing regimen, (2) study naltrexone effects on the acquisition of
      ethanol drinking, and (3) study the effects of chronic naltrexone from timed
      release pellets on drinking in alcohol-naive mice. Naltrexone reduced ethanol
      preference in established drinkers, but its effects waned at increasing doses.
      Naltrexone slowed the acquisition of ethanol drinking, but was ineffective when
      readministered after a phase when ethanol was offered in the absence of
      naltrexone. Mice with chronic naltrexone pellets consumed greater amounts of
      ethanol and showed higher ethanol preference than did placebo-pelleted animals.
      The observed reduced efficacy of naltrexone with increasing dosage and chronic
      treatment may have been due to naltrexone-induced opiate receptor changes. Such
      changes are presumably more likely to occur when naltrexone doses remain high or
      perhaps accumulate. Thus, dose and frequency of administration may be important
      factors in determining naltrexone's effectiveness in treating alcohol dependence.

PMID- 9194925
TI  - Interactions between alcohol- and opioid-induced suppression of rat testicular
      steroidogenesis in vivo.
AB  - To examine interactions between alcohol and endogenous opioids in their
      suppressive effects on rat testicular function, the opioid antagonist naltrexone
      or the opioid agonist morphine was administered to adult male rats alone or in
      combination with alcohol. Serum testosterone, testicular interstitial fluid (TIF)
      testosterone, and TIF volumes were measured to assess testicular function.
      Naltrexone induced dose-dependent increases in serum and TIF testosterone levels
      without changes in TIF volume. Alcohol (0.5 g/kg) inhibited naltrexone-induced
      stimulation of testosterone secretion and shifted the naltrexone dose-response
      curve to the right. Conversely, naltrexone (0.05 mg/kg) inhibited alcohol-induced
      suppression of testosterone secretion and shifted the alcohol dose-response curve
      to the right. Relatively high doses of naltrexone (5 to 30 mg/kg) were needed to
      stimulate testosterone secretion maximally in rats treated with a low dose of
      alcohol (0.5 g/kg) and to stimulate normal levels of testosterone secretion in
      rats treated with a high dose of alcohol (2 g/kg). In addition, combined
      treatment with 1 and 30 mg/kg of naltrexone and 0.5 to 2 g/kg of alcohol did not
      alter blood alcohol concentrations significantly, suggesting that the
      interactions between alcohol and naltrexone were unrelated to gross changes in
      alcohol metabolism or bioavailability factors. Simultaneous treatments with a low
      dose of alcohol (0.3 g/kg), near the threshold of efficacy, and low-moderate
      doses of morphine (0.3 to 3 mg/kg) were not additive in suppressing testosterone
      secretion, compared with either agent alone. These results support the hypothesis
      that opioid antagonists can reverse the suppressive effect of alcohol on
      testicular steroidogenesis, but the results also suggest that endogenous opioids
      do not exclusively mediate alcohol's effects on testosterone secretion.

PMID- 9194927
TI  - Somatostatin-stimulated growth hormone-releasing factor secretion in vitro is
      modified by fetal ethanol exposure.
AB  - Exposure to ethanol (ETOH) in utero has been found to alter the growth hormone
      (GH)/insulin-like growth factor axis and retard growth. GH release is regulated
      by the interaction of the hypothalamic hormones somatostatin [somatotropin
      release inhibiting factor (SRIF)] and GH-releasing factor (GRF). Communication
      between these factors occurs at both the hypothalamic and pituitary levels. In
      this study, we examined the effect of fetal ETOH exposure on the postnatal
      development of SRIF regulation of GRF release at the hypothalamic level. The
      studies were conducted on hypothalami from 30- and 60-day-old pups in an in vitro
      perfusion system. SRIF was tested against K(+)-induced GRF release. Basal GRF
      release, not in the presence of external stimuli, from the hypothalami of ETOH
      exposed pups (both male and female) was greater than GRF release from tissue of
      offspring of both pair-fed and control dams. GRF release was also greater in
      female, compared with male hypothalami, and the effect of ETOH was more
      pronounced at 30, compared with 60, days of age. The heightened release of GRF
      may reflect reduced sensitivity to feedback regulation by GH in ETOH-exposed
      pups. Furthermore, fetal ETOH exposure reversed the effect of SRIF modulation on
      K(+)-induced GRF release. In hypothalami from offspring of both pair-fed (except
      30-day-old females) and ad libitum-fed controls, SRIF enhanced the K(+)-induced
      GRF release. In tissue from ETOH-exposed pups (except 60-day-old males), GRF
      release was inhibited by SRIF. We suggest that this pattern may reflect a change
      in the characteristics of SRIF connections with GRF neurons by ETOH. In summary,
      this data indicates that both basal and SRIF-stimulated GRF is altered by ETOH
      and that effect remains significantly altered at least until puberty.

PMID- 9194928
TI  - Fetal alcohol exposure produces delay-dependent memory deficits in juvenile and
      adult rats.
AB  - The effects of prenatal alcohol exposure on both behavioral and neurobiological
      measures may be dependent, in part, on the age of the animal. Previous evidence
      from our laboratory has shown a delay-dependent memory deficit in young adult
      fetal alcohol exposure (FAE) rats. The present study examined the effects of FAE
      on an alternation task at three different ages of male rats: juvenile (days 38 to
      44), young adult (days 82 to 89), and adult (days 173 to 180). In the present
      study, subjects were three age groups of male offspring of Sprague-Dawley rats
      fed 35% ethanol-derived calories, pair-fed with sucrose, or control-fed with lab
      chow during the last week of gestation. Subjects were food-deprived before
      training and then trained in the T-maze for food reward. Rats were trained to
      alternate at no delay on six sessions over 3 days. On each of the next 4 days,
      rats were tested for two sessions at delays of 10 sec, 30 sec, 60 sec, and then a
      no-delay condition. On the final day of testing, rats were tested at the 60-sec
      delay for 10 trials. No FAE effect was observed at the short delay during the
      training sessions; however, the adult group had a lower performance on the
      training sessions, compared with the other groups. In the test session, the FAE
      groups showed a delay-dependent memory deficit. FAE rats in all three age groups
      were impaired at the 30-sec and 60-sec delays, compared with their control
      groups. However, only the juvenile FAE rats were impaired at the 10-sec delay,
      compared with the control groups. The FAE groups were not impaired when tested
      again at no delay. These findings indicate long-term consequences of prenatal
      alcohol exposure in rats on memory retention that is present up to 6 months of
      age. In addition, the finding that only the juvenile FAE rats showed impairment
      at the 10-sec delay indicates that certain deficits may decrease as the FAE rat
      matures.

PMID- 9194929
TI  - Chronic ethanol inhibits inositol metabolism in specific brain regions.
AB  - Many neurotransmitters and hormones in the nervous system transmit signals
      through receptors coupled to the poly-phosphoinositide (PI) signaling pathway. In
      this study, an in vivo protocol with [3H]inositol was used to examine the effect
      of chronic ethanol administration on inositol metabolism and poly-PI turnover in
      the cerebral cortex, hippocampus, and cerebellum of mouse brain. C57BL/6 mice
      were given a nutritionally complete liquid diet containing either ethanol (5%,
      w/v) or isocaloric sucrose for 2 months. Mice were injected intracerebrally with
      [3H]inositol; after 16 or 24 hr, they were injected intraperitoneally with
      lithium (8 mEq/kg body weight) to inhibit the inositol monophosphatase (IP1)
      activity. All mice were decapitated 4 hr after lithium injection. Labeled
      inositol phospholipids accounted for 16 to 23% of total labeled inositol in
      different regions of control mouse brain, and the percentages in the hippocampus
      were consistently higher than the cerebral cortex and cerebellum. In control
      mice, the percentages of labeled IP1 after a 4-hr lithium treatment were 11.5%,
      9.9%, and 3.7% for cerebral cortex, hippocampus, and cerebellum, respectively.
      Chronic ethanol feeding resulted in a significant (p < 0.05) decrease in the
      percent of labeled IP1 and inositol phospholipids, and this effect was observed
      in the cerebral cortex and, to a lesser extent, hippocampus but not cerebellum.
      When ratios of labeled IP1 were expressed against labeled inositol phospholipids
      as an index of the poly-PI turnover activity, significant decreases in IP/lipid
      ratios were observed in the cerebral cortex, but not the hippocampus or
      cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would
      have experienced an 8-hr period of ethanol withdrawal, compared with the 16 + 4
      hr group, no differences in IP/lipid ratios were observed between the two time
      groups. These results illustrate regional differences in the effect of chronic
      ethanol on inositol metabolism in the brain, but no difference in poly-PI
      turnover in brain due to ethanol withdrawal.

PMID- 9194931
TI  - The role of cAMP in ethanol-regulated beta-endorphin release from hypothalamic
      neurons.
AB  - We have previously shown that ethanol acutely stimulates immunoreactive beta
      endorphin (IR-beta-EP) release from hypothalamic neurons, whereas chronic
      administration of ethanol desensitizes these neurons. In the study reported
      herein, the role of the intracellular cAMP system in the ethanol-regulated IR
      beta-EP release from hypothalamic cells in primary cultures was investigated.
      Acute treatment with ethanol or with the cAMP analog, dibutyryl cAMP, revealed
      that both agents stimulate the release of IR-beta-EP from the hypothalamic cells.
      Combined treatment of ethanol and the cAMP analog produced a synergistic effect
      on IR-beta-EP release. Treatment with ethanol and a cAMP-elevating agent,
      forskolin, increased cAMP levels in cultured hypothalamic cells. However, prior
      exposure to ethanol reduced the cAMP-elevating responses of these neurons to
      ethanol and forskolin. These results indicate that the stimulatory and adaptive
      responses of IR-beta-EP neurons to ethanol may involve the cAMP system.

PMID- 9194930
TI  - Effect of chronic ethanol exposure on myocardial phosphoinositide turnover.
AB  - The effect of chronic ethanol consumption (2 months) on atrial contractility and
      the myocardial phosphoinositide signaling system was examined in rat heart. Two
      months of ethanol consumption was not associated with changes in heart weight-to
      body weight ratios; however, developed twitch tension was significantly lower in
      the ethanol atria compared with the control atria. Cytosolic and membrane
      associated phospholipase C activity in atrial and ventricular tissue was measured
      and ethanol consumption was only associated with changes in ventricular cytosolic
      phospholipase C activity. When examining alpha(1)-adrenergic stimulated
      phosphoinositide turnover in [3H]inositol radiolabeled left atria, no differences
      in phenylephrine (10 microM)-stimulated inositol monophosphate, inositol
      bisphosphate, inositol trisphosphate, and inositol tetrakisphosphate were found
      between groups before or at various times after the addition of phenylephrine. It
      is concluded that short-term ethanol consumption is associated with depressed
      contractile function, but not the development of hypertrophy or changes in
      alpha(1)-adrenoreceptor-stimulated phosphoinositide turnover.

PMID- 9194932
TI  - Liver regeneration attenuates increased voluntary alcohol intake evoked by the
      liver damage.
AB  - Liver dysfunction induced in Wistar rats either surgically (by construction of
      portocaval anastomosis) or chemically (by chronic administration of
      thioacetamide) led to increased voluntary alcohol intake. Alcohol preference
      could be attenuated by liver regeneration that was triggered by a two-thirds
      hepatectomy done on cirrhotic rats. The brain serotonin system was activated in
      portocaval anastomosis rats and unchanged in thioacetamide-treated rats, thus
      suggesting that serotonin is not likely to be implicated in the mechanism(s)
      underlying development of alcohol preference in these rats. Also, tetrahydro-beta
      carboline could possibly be excluded from consideration. Neither change in the
      brain concentration or distribution of tetrahydrobetacarboline after long-term
      treatment with thioacetamide could be found.

PMID- 9194933
TI  - Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats:
      a stereological study of temporal windows of vulnerability.
AB  - Previous research has shown that the early neonatal period of rats is one of
      enhanced vulnerability to cerebellar Purkinje cell loss associated with binge
      like alcohol exposure, with a prominent sensitive period during the first
      neonatal week. In this study, an unbiased count of the total number of Purkinje
      cells was obtained using the stereological optical fractionator, in groups of
      rats given a single binge-like alcohol exposure either during the most vulnerable
      neonatal period [postnatal day (PD) 4] or during a later, less vulnerable period
      (PD 9). Using artificial rearing methods, rats were given 6.6 g/kg of alcohol
      either on PD 4 or on PD 9, delivered as a 15% (v/v) solution in milk formula on
      two consecutive feedings of the designated day. Control groups included an
      artificially reared gastrostomy control and a normally reared suckle control. The
      mean peak blood alcohol concentrations were not different between the PD 4 and PD
      9 alcohol groups, averaging 374 and 347 mg/dl, respectively. The rats were
      perfused on PD 27. A uniform random sample of sections was obtained from serial
      frozen sections through the cerebellum, stained with thionin, and Purkinje cells
      were counted from a uniform random sample of locations on each section with the
      three-dimensional optical fractionator. The number of Purkinje cells in the
      suckle control and gastrostomy control groups did not differ from each other,
      averaging 3.94 (+/- 0.19) and 3.58 (+/- 0.22) x 10(5) cells, respectively. Binge
      exposure on PD 4 induced significant cell loss (mean of 2.05 +/- 0.20 x (10(5)
      Purkinje cells), whereas binge exposure on PD 9 did not induce significant
      Purkinje cell loss (3.70 +/- 0.39 x 10(5) Purkinje cells). These findings confirm
      that a single neonatal binge alcohol exposure produces pathological Purkinje cell
      loss, provided that it occurs during the period of enhanced vulnerability
      coinciding with the early stages of dendritic outgrowth.

PMID- 9194934
TI  - Acute ethanol effects on focal cerebral ischemia in nonfasted rats.
AB  - Focal cerebral ischemia was induced in a rat model of middle cerebral artery
      occlusion. Three groups of adult male Sprague-Dawley rats, given food and water
      ad libitum, were subjected to 4 hr of middle cerebral artery occlusion. All were
      given vehicle control and ethanol pretreatments intraperitoneally 1 hr before.
      Mean ipsilateral brain water content in the control, 2 g/kg ethanol, and 2 g/kg
      ethanol + insulin-treated groups showed: ischemia core: 81.1%, 82.5%, and 80.9%;
      intermediate zone: 81.0%, and 80.3%; and outer zone: 80.3%, 81.3%, and 80.1%,
      respectively. Brain Na+ and K4 content in these groups paralleled the water
      content. In addition to significantly (p < 0.05) more brain edema, the 2 g/kg
      ethanol-treated animal group also had significant hyperglycemia. In contrast, the
      2 g/kg ethanol + insulin-treated animals were normoglycemic and had ischemic,
      intermediate, and outer zone Na+, K+, and Cl- levels comparable with the control
      group (p > 0.05). These results stress the importance of measuring and
      controlling plasma glucose levels in the in vivo studies of the neurotoxic
      effects of acute ethanol.

PMID- 9194935
TI  - Ethanol-reinforced responding by AA and ANA rats following the sucrose
      substitution initiation procedure.
AB  - Ethanol-reinforced responding was initiated in male AA and ANA rats using the
      sucrose-substitution procedure. Before the initiation procedure, a homecage, two
      bottle preference test was conducted. The rats were then trained to respond on an
      Fixed-Ratio 1 schedule with sucrose reinforcement. Over sessions, ethanol was
      added gradually to the sucrose solution as the concentration of sucrose was
      reduced until 10% ethanol (v/v) alone functioned as the reinforcer for lever
      pressing. The schedule of reinforcement was then increased to Fixed-Ratio 4.
      Next, the ethanol concentration presented as the reinforcer was increased over
      weeks to 15%, 20%, 30%, and then returned to 10%. A second homecage test was then
      performed. The results showed that the AA and ANA lines differed significantly on
      preference and intake (g/kg) during the homecage preference tests. There was a
      significant increase in preference during the second homecage test. During
      sucrose substitution, initial large differences in responding were observed
      between the lines. When the ethanol concentration was increased, intake (grams
      per kilogram) increased for the AA line but not for the ANA line. These effects
      were a function of no change in responding by the AA rats as concentration was
      increased and a decrease in responding by the ANA rats at the higher
      concentrations (20% and 30%). Taken together, data indicate that ethanol can
      function as a positive reinforcer for the behavior of AA and ANA rats. Even
      though 10% ethanol functioned as a reinforcer similarly for the two lines,
      ethanol intake in the AA line was significantly greater at the higher
      concentrations of ethanol, suggesting that ethanol functioned as a qualitatively
      different reinforcer for the AA rats, compared with the ANA rats.

PMID- 9194936
TI  - Characterization of the mu and delta opioid receptors in the brain of the C57BL/6
      and DBA/2 mice, selected for their differences in voluntary ethanol consumption.
AB  - Genetically determined differences in the activity of the hypothalamic beta
      endorphin system have been demonstrated between the C57BL/6 (alcohol-preferring)
      and DBA/2 (alcohol-aversive) inbred strains of mice. The present studies examined
      the distribution and density of the mu and delta receptors in specific brain
      regions that may mediate the rewarding and reinforcing effects of ethanol, using
      quantitative autoradiography and the specific mu agonist FK 33-824 and delta
      agonist DPDPE, in their iodinated form. 125I-FK 33-824 recognizes a high affinity
      binding site in brain membrane preparations from both the C57BL/6 (Kd = 1.37 +/-
      0.22 nM; Bmax = 80 +/- 12.3 fmol/mg protein) and DBA/2 mice (Kd = 1.02 +/- 0.16
      nM; Bmax = 39.5 +/- 9.6 fmol/mg protein), whereas 125I-DPDPE binds to a high
      affinity binding site in brain membranes from both the C57BL/6 (Kd = 1.08 +/-
      0.34 nM; Bmax = 24.4 +/- 4.5 fmol/mg protein) and DBA/2 mice (Kd = 0.68 +/- 0.24
      nM; Bmax = 15.3 +/- 3.7 fmol/mg protein). The autoradiographic studies
      demonstrated differences in the density of the mu opioid receptors between the
      two strains of mice in brain nuclei that are not directly related to the brain
      reward system. However, strain-related differences in the density of delta opioid
      receptors were observed in regions of the limbic system known to mediate the
      positive reinforcing effects of many drugs of abuse. The density of delta
      receptors was significantly higher in the ventral tegmental area and nucleus
      accumbens of the C57BL/6 mice. The results of the present study support the
      hypothesis that genetically determined differences exist in the density of opioid
      receptors in distinct regions of the brain between the C57BL/6 and DBA/2 inbred
      strains of mice, which may play a role in controlling their voluntary ethanol
      consumption.

PMID- 9194937
TI  - Manipulation of alcohol drinking by liver transplantation.
AB  - The procedure of liver transplantation in alcoholic liver disease raises the
      question whether it would be possible to regulate the recipient's future drinking
      by the choice of donor liver. To address this question, we conducted
      transplantations with rat lines selected for high (AA) and low (ANA) alcohol
      preference. AA recipients having alcohol experience before the operation remained
      heavy drinkers regardless of whether the graft came from an AA or ANA donor.
      However, in these AA recipients who started drinking only after the operation,
      differences emerged, with AA grafts creating heavy drinking and ANA donor livers
      resulting in very low drinking. An overall increase in the acetaldehyde levels
      was introduced by the ANA livers, thus reflecting the original line differences.
      Similarly, in subsequent experiments, it was observed that when the aldehyde
      dehydrogenase inhibitor calcium carbimide was introduced in different amounts to
      the diet, alcohol drinking was reduced more in animals not used to drinking. The
      magnitude of this effect, especially in situations with established heavy
      drinking, is of relevance in future contemplations about liver transplantations
      between humans with different aldehyde dehydrogenase genotypes.

PMID- 9194938
TI  - Otitis media and its relation to allergic rhinitis.
AB  - Otitis media is a multifactorial illness that is the most common childhood
      disease that requires physician care, and its resultant health care costs are
      high. The established role of infection in the pathogenesis of otitis media has
      promoted aggressive antimicrobial therapy with specific antibiotic protocols for
      acute otitis and prophylactic antibiotic regimens for chronic or recurrent acute
      otitis media. Even though these antibiotic regimens have been widely used, there
      has not been a decreased incidence of otitis media and its complications. The
      possibility that allergy contributes to chronic or recurrent otitis media
      especially in children older than 3 years has been debated for years. If a causal
      relationship between allergic respiratory diseases and middle ear disease were to
      be established, then one would anticipate that anti-allergic therapy would reduce
      the morbidity and health care costs associated with otitis media.

PMID- 9194939
TI  - Immunologic considerations in the child with recurrent or persistent sinusitis.
AB  - The diagnosis and management of chronic sinusitis in children represents a
      difficult challenge for the clinician. Part of the problem stems from the fact
      that normal children have many upper respiratory infections and it is sometimes
      difficult to determine whether the upper respiratory symptoms a child experiences
      with these infections are consistent with a normal number of "routine" childhood
      infections or whether there is a more significant problem. The issue is
      complicated by the fact that sinus infections in children may not have the same
      clinical manifestations as similar infections in adults. This review focuses on
      the pathophysiology of persistent and chronic sinus infections in children.
      Particular emphasis is placed on the potential role for allergic and/or
      immunologic disorders in children with chronic sinus problems.

PMID- 9194940
TI  - A cost-effective approach to the diagnosis and treatment of the wheezing infant.
AB  - Wheezing in infancy presents the clinician with at least two broad clinical
      problems. First is the task of distinguishing the common entities of
      bronchiolitis and asthma from rare, yet potentially life threatening illnesses
      that may present with wheezing. The second problem deals with the difficulties in
      distinguishing an infant with an isolated episode of wheezing with an upper
      respiratory tract infection from those infants who are at risk for persistence of
      wheezing through infancy. When confronted with a wheezing infant, a family may
      appropriately have the following questions: Is this asthma? What testing is
      needed? What risk for recurrence is present? A physician may focus similarly on
      the issue of risk of persistence of wheezing and be left with the difficult
      decisions of the cost and benefit of different diagnostic and therapeutic
      modalities. In order to best address these questions, a brief review of the
      pathophysiology, clinical, and epidemiological features associated with wheezing
      in infancy is offered.

PMID- 9194941
TI  - Treatment of the unusually difficult asthmatic patient.
AB  - Various practice parameters have emphasized a step-wise approach to the treatment
      of asthma utilizing high doses of inhaled corticosteroids, i.e., 2000 ug per day
      for the most difficult-to-manage asthmatic patient, along with maximum
      bronchodilator therapy. The use of such vigorous therapy presupposes that various
      triggers that perpetuate asthma have been considered and hopefully eliminated or
      diminished, such as occupational incitants, gastroesophageal reflux, and
      concomitant medication such as beta blockers and perhaps difficult-to-recognize
      allergen stimulation. As new therapies emerge, their role in the treatment of a
      severe subgroup of the population remains uncategorized and will only be
      clarified with personal experience and appropriate double-blind studies. For
      example, there are data to support the concept that salmeterol plus moderate dose
      aerosol corticosteroids is superior to high dose corticosteroid aerosols.
      Theoretically, the use of anti-leukotrienes for a patient with aspirin
      idiosyncrasy may be superior to other combinations as would be conjectured from
      aspirin challenge data. Lidocaine has recently been employed in severe
      asthmatics, and preliminary data suggest benefit. The purpose of this review is
      to summarize some of our knowledge regarding medications that are either steroid
      sparing or that might be useful in a subgroup of asthmatic patients with severe
      asthma.

PMID- 9194942
TI  - Does allergen immunotherapy have a role in the treatment of bronchial asthma?
AB  - There is evidence from epidemiologic studies, supported by more intensive study
      of selected groups of subjects, for the importance of allergy in initiating and
      contributing to the severity of bronchial asthma. Furthermore, removal of
      allergen exposure is followed by improvement in both symptoms and evidence of
      airway inflammation. Allergen immunotherapy reduces the sensitivity of the
      respiratory tract to allergens, blocks the influx of eosinophils and mucosal mast
      cells in response to allergen exposure, and alters the pattern of cytokine
      release by T-lymphocytes, generally decreasing Th2-related cytokines (IL-4) and
      increasing those related to the Th1 response (interferon-gamma, IL-2, IL-12). It
      would be remarkable, given these alterations in responsiveness produced by
      allergen immunotherapy, if this treatment were not effective in bronchial asthma.
      Indeed, an analysis of controlled studies of allergen immunotherapy does indicate
      that it is clinically effective in carefully selected, allergic asthmatics.

PMID- 9194943
TI  - Particulate air pollution: possible relevance in asthma.
AB  - The relative importance of air pollution in the pathogenesis of bronchial asthma
      has been of interest for several decades. Numerous studies on the role of gaseous
      air pollution containing ozone, nitrogen dioxide, sulfur dioxide, and carbon
      monoxide have been published. Very little attention has been focused on the role
      of respirable particles in the causation of asthma. In this article we summarize
      some of our ongoing investigations into the sources and composition of airborne
      particles in the Los Angeles and Pasadena atmosphere, including the search for
      biologically active particles that may induce asthma attacks. If is found that
      the urban atmosphere contains not only combustion-derived particles from diesel
      engine exhaust and gasoline-powered motor vehicle exhaust, but also particles
      formed from biological starting materials including plant debris, cigarette
      smoke, wood smoke, and meat smoke as well as tire debris containing some natural
      rubber and paved road dust. Paved road dust is a very complex mixture of
      particles including garden soil, tire dust, plant fragments, redeposited
      atmospheric particles of all types, and pollen fragments presumably ground up by
      passing traffic. We have shown previously that latex allergen can be extracted
      from tire dust, from roadside dust, and from respirable air samples taken at Los
      Angeles and Long Beach. At present, work is underway to identify the larger range
      of allergens that may be contributed by the entrainment of paved road dust into
      the atmosphere. The possible importance of pollen fragments present in paved road
      dust in very small particle sizes is discussed as well as their potential
      relevance in asthma.

PMID- 9194944
TI  - Sinusitis in an allergist's office: analysis of 200 consecutive cases.
AB  - Sinusitis affects up to 14% of Americans. Traditionally, most patients with
      sinusitis are evaluated and treated by either primary care physicians or
      otolaryngologists. In order to gain information regarding the characteristics at
      presentation and the outcome of treatment of sinusitis by an allergist, the
      records of 200 consecutive patients seen at the Institute for Asthma and Allergy
      at the Washington Hospital Center for chronic sinusitis were reviewed. The most
      common presenting symptoms were nasal congestion, postnasal drip, purulent
      rhinorrhea, headache, cough, facial pressure, anosmia or hyposmia, hypogeusia,
      and throat clearing. Initial abnormal physical exam findings included abnormal
      transillumination, purulent secretions, nasal mucosal swelling, nasal polyps, and
      nasal crusting. Treatment included 4 weeks of oral antibiotics, nasal
      corticosteroids, nasal lavage, and topical decongestants. All of the presenting
      symptoms (23-75% of the patients) and signs (50-84% of patients) improved with
      medical management. Patients have been followed for 1 to 27 months, with a mean
      of 6 months, and 6% have required surgery, with one complication of cerebrospinal
      fluid leak. These findings indicate that medical management of chronic sinusitis
      in an allergist's office is effective.

PMID- 9194945
TI  - Distribution of Dermatophagoides spp., D. farinae and D. pteronyssinus, antigen
      in homes of patients with asthma in eastern Massachusetts.
AB  - Regional analysis of dust mite species distribution is pertinent to clinical
      practice as atopic patients should be tested and, when indicated, receive
      appropriate immunotherapy with house dust mite antigens indigenous to their
      geographic locale. Surveys in selected areas of the United States have found D.
      farinae and D. pteronyssinus to be the two most prevalent mite species. None of
      these surveys encompassed the populous Northeastern corridor of the United
      States. This present study describes the distribution of Dermatophagoides spp.
      antigens within the homes of asthma sufferers living in suburban Massachusetts. A
      total of 60 dust samples were collected from carpets in the homes of 46 patients
      with chronic asthma and documented house dust mite sensitivity. Dust samples were
      obtained from bedroom carpets in 46 homes and both bedroom and family room
      carpets in 14 homes. Dermatophagoides spp. bedroom carpet levels ranged from 2.3
      ug/g to 138.5 ug/g; (mean level 36.1 ug/g). D. farinae was the dominant species
      in the majority (78%) of sampled homes. D. pteronyssinus predominated in only
      three (7%) homes. Nearly 80% of surveyed homes and carpet dust mite antigen
      levels exceeding 10 ug/g. Mean bedroom carpet levels were more than two-fold
      higher than family room levels, 47.7 ug/g versus 19.5 ug/g. Distribution patterns
      of D. farinae and D. pteronyssinus in bedroom and living room carpets was similar
      in 13 of 14 surveyed homes. Although D. farinae is clearly the dominant allergen
      in the surveyed homes, this study suggests that both D. farinae and D.
      pteronyssinus antigens should be used for diagnostic testing and, when indicated,
      immunotherapy in the northeastern United States.

PMID- 9194946
TI  - Asthma among the famous. Tseng Kuo-Fan (1811-1872) Chinese Scholar, statesman,
      and general.

PMID- 9194947
TI  - Asthma among the famous. Austin Flint (1812-1886) American physician.

PMID- 9194948
TI  - Asthma among the famous. Henry Ward Beecher (1813-1887) American churchman and
      orator.

PMID- 9194949
TI  - Asthma among the famous. Charles H. Blackley (1820-1900) British physician.

PMID- 9194950
TI  - The Jewish physician in the post Columbus era: the 15th century Spanish
      inquisition and expulsion revisited in 20th century Germany and Austria.

PMID- 9194951
TI  - Guidelines for early identification of Alzheimer Disease.

PMID- 9194952
TI  - The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO
      single-photon-emission computed tomography for the diagnosis of Alzheimer disease
      in a community-dwelling elderly population.
AB  - The objective of this study was to assess the diagnostic value for Alzheimer
      disease (AD) of single-photon-emission computed tomography (SPECT) and magnetic
      resonance imaging (MRI), separately and in combination. The study was part of a
      two-stage population-based study of mental functioning among noninstitutionalized
      65-to 85-year-olds living in Amsterdam, The Netherlands. Participants (n = 51)
      were randomly selected within strata of cognitive function to obtain a sample of
      AD patients (n = 10) and clinically normal subjects (n = 41), of whom 22
      displayed some cognitive impairment and fulfilled criteria for "minimal dementia"
      according to the Cambridge Examination for Mental Disorders of the Elderly.
      Coronal T1-weighted MRI was used to visualize the medial temporal lobe. Medial
      temporal lobe atrophy (MTA) was assessed qualitatively on a 0-4 scale. Regional
      cerebral blood flow on SPECT was assessed with the use of technetium 99m-HMPAO in
      three manually drawn regions of interest (frontal, parietal, and
      temporoparietal). Ratios were calculated by using the cerebellum as the reference
      area. MTA differed significantly between AD patients and clinically normal
      subjects (p = 0.0009), with sensitivity for AD of 70% and a specificity of 76%.
      None of the three SPECT ratios differed between normal and AD subjects. The
      temporoparietal/cerebellar ratio had a sensitivity of 30% and a specificity of
      71% as a cutoff of 0.76. When both tests were positive the combined sensitivity
      was low (20%), but the false-positive rate was also very low (5%). A negative
      result on MRI or any SPECT ratio yielded a high specificity (93%-98%) but also a
      high false-negative rate (60-80%). Adding SPECT to MRI seems useful only if a
      diagnosis of AD is suspected clinically and confirmation is needed. When the
      clinical probability that AD is absent is high, normal results on either MRI or
      SPECT may confirm this notion. Given the fact that structural imaging should be
      performed in a clinical workup for dementia, using MRI only would be the most
      cost-effective approach.

PMID- 9194953
TI  - The Bedford Alzheimer Nursing Severity scale for the severely demented:
      validation study.
AB  - We evaluated the floor effect and convergent, discriminant, and known-group
      validity of the Bedford Alzheimer Nursing Severity scale (BANS-s), a rating scale
      comprising cognitive and functional items recently developed for grading severe
      dementia. Ninety-nine demented patients (81 females and 18 males aged 55-100
      years) in two nursing homes were assessed with the BANS-s, established cognitive
      and functional scales [Mini Mental State Examination, the extended version of the
      Clinical Dementia Rating (CDR), Katz's basic activities of daily living, Tinetti
      balance and gait, and Crichton scales], a behavioral scale (UCLA Neuropsychiatric
      Inventory), and indicators of malnutrition (Prognostic Nutritional Index). A
      relevant proportion (40%) of patients scored close to the floor of all scales
      except BANS-s and CDR, which showed a more uniform distribution of scores
      throughout the possible range. Convergent validity of BANS-s with the other
      cognitive and functional scales was good, with Pearson's r ranging from 0.62 to
      0.79. Discriminant validity analysis of BANS-s versus the UCLA Neuropsychiatric
      Inventory showed that the two scales measure different domains (Pearson's r =
      0.36). To test known-group validity, all patients were divided into two groups of
      different severity as defined by the Prognostic Nutritional Index. BANS-s and CDR
      were the scales with the best ability to discriminate malnourished from
      nonmalnourished patients. As a further validity test, the 37 patients reaching
      the floor on other cognitive and functional scales were divided into two
      subgroups of different dementia severity as defined by the Tinetti scale. BANS-s
      but not CDR was able to differentiate the two groups.

PMID- 9194954
TI  - Blood-cerebrospinal fluid barrier dysfunction for high molecular weight proteins
      in Alzheimer disease and major depression: indication for disease subsets.
AB  - There is a diversity of opinions concerning the function of the blood-brain
      barrier and the blood-cerebrospinal fluid barrier (BCB) in Alzheimer disease and
      other neuropsychiatric disorders. In this paper we investigate and review the
      evidence for BCB dysfunction in Alzheimer disease and major depression. The
      hypothetical roles of immunologically mediated mechanisms in the central nervous
      system (CNS) are discussed. Special consideration is given to methodological
      factors influencing BCB function and analysis. Serum and cerebrospinal fluid
      (CSF) of 29 patients with major depression (MD) and 51 patients with "probable
      Alzheimer disease" (AD) were investigated. The AD patients were subdivided in two
      groups of 21 early-onset (EO) and 30 late-onset (LO) cases and assayed for
      concentrations of albumin and IgG. The results were compared with those for 11
      age-matched healthy controls. The severity of dementia was assessed with the Mini
      Mental State Examination (MMSE). AD and MD patients showed significantly lower
      serum albumin [AD: p < 0.05 (LO: p < 0.038); MD p < 0.01] and IgG (AD: p < 0.01;
      MD: p < 0.013) concentrations compared with controls. MD (p < 0.001) and LO-AD (p
      < 0.07) patients displayed significantly lower absolute serum albumin levels than
      did EO-AD patients. The CSF/serum ratio for albumin and IgG was used to evaluate
      BCB function. There were no significant group differences; however, subsets of MD
      (29%) and AD (16%) patients showed a higher frequency of a pathological albumin
      ratio than did control subjects. Furthermore, a subset of 24% of MD and18% of AD
      patients and none of the controls showed an elevated IgG ratio. Different
      mechanisms of alteration of IgG distribution are presented. The degree of
      cognitive impairment in AD did not correlate positively with protein and ratio
      parameters. The BCB is critical to the maintenance of homeostasis within nervous
      system tissue. We suggest that the altered function can result from immune
      mediated events such as altered levels of circulating inflammatory mediators.
      Furthermore, we assume that in the AD and MD subgroups, the BCB dysfunction for
      high molecular weight proteins permits access of components of the immune system
      to the CNS, which may contribute to disease pathology.

PMID- 9194955
TI  - Alzheimer-like visual deficits in Down syndrome.
AB  - Patients with Alzheimer disease (AD) show visual impairments in color
      discrimination (blue hues), stereoacuity, and contrast sensitivity. We asked
      whether the AD-type visual profile occurs in Down syndrome (DS) in light of the
      fact that AD neuropathology is present in DS by age 40. We tested 22 adults with
      DS and 18 adults with mental retardation of non-DS etiology (MR). DS subjects
      made more tritanomalous errors on the test of color vision than predicated by
      chance (p < 0.05), indicating a deficiency in the discrimination of short
      wavelengths (blue hues) but not more of other types of hue discrimination errors.
      DS subjects had higher stereoacuity thresholds than MR subjects (p < 0.01) and
      reduced contrast sensitivity across the frequency range (p < 0.01). Taken
      together, the results point to AD-like visual deficits in DS. Like classic AD, DS
      may be associated with pathological changes in the parastriate and peristriate
      visual cortex. DS performance was not correlated with age, suggesting that in
      individual subjects, the AD-like visual deficits may present prior to and
      independent of age-associated dementia.

PMID- 9194956
TI  - Knowledge about Alzheimer disease among primary care physicians, psychologists,
      nurses, and social workers.
AB  - Although much of the care of Alzheimer disease (AD) patients and their families
      is carried out by health professionals who are not specialists in AD or
      geriatrics, little is known about how knowledgeable these health professionals
      are about AD. An AD knowledge test was constructed through careful instrument
      development procedures and then administered through a mail survey. Subjects were
      693 individuals, including experts in AD care, generalist health care
      professionals (primary care physicians, psychologists, social workers, and
      nurses), nursing students, hospital staff nurses, and assorted health
      professionals. A 12-item scale with excellent psychometric properties was
      developed. Experts in AD care performed significantly better than generalist
      health care professionals on all items. All four groups of generalist health care
      professionals showed important deficits in fundamental knowledge about AD; for
      example, only 40% of generalists (vs. 97% of experts) knew that AD is the most
      common cause of severe memory loss in people over age 65. Results suggest that,
      although knowledge about assessment and management of AD has increased and has
      been widely disseminated, many health care professionals remain uninformed about
      AD. Suggestions for professional education and for use of the UAB AD Knowledge
      Test for Health Professionals are discussed.

PMID- 9194957
TI  - Familial Alzheimer disease: first report from India.

PMID- 9194958
TI  - Delusions of theft in dementia of the Alzheimer type: a preliminary report.
AB  - Delusions of theft are commonly found in patients with dementia of the Alzheimer
      type (DAT). This report describes the frequency, onset, and characteristics of
      delusions of theft in DAT patients. The sample consisted of 54 geropsychiatric
      inpatients with DAT; delusions of theft were found in 30 (55.6%) patients. Two
      thirds of these patients had delusions of theft within 1 year after onset of
      illness. There were no significant differences in age, age of onset, duration of
      disease, years of education, or the Mini-Mental State Examination (MMSE) score
      between patients with and without delusions of theft. Delusions of theft
      frequently occur in the early stage of dementia, when the patients' cognitive
      impairments are relatively mild. The presence of this symptom may warrant a
      diagnosis of DAT.

PMID- 9194959
TI  - Meeting report: the Fifth International Conference on Alzheimer's Disease and
      Related Disorders.

PMID- 9194960
TI  - Clinical and research issues on older drivers: future directions.
AB  - This article serves as an overview of both clinical and research issues relevant
      to enhancing the safety of older drivers. Even though the vast majority of older
      drivers are safe on the road, physicians and other health care providers need
      tools and mechanisms for identifying those older drivers who are a safety risk
      because of cognitive, sensory, and/or other medical impairments. Research in this
      field tends to have either of two related goals: (1) to help older drivers stay
      on the road as long as it is safely possible to do so, through identifying and
      rehabilitating those with impaired skills, and (2) to identify transportation
      alternatives to driving for those older adults faced with driving cessation.
      Driving is discussed as an activity of daily living within the broader context of
      mobility, and as such is tied to quality of life.

PMID- 9194961
TI  - Evaluating the driving competence of dementia patients.
AB  - The driving behaviors of dementia patients have received little in the way of
      empirical scrutiny except through retrospective reports of crash rates.
      Understanding the driving errors of dementia patients and how they differ from
      those of normal older and younger drivers is important. This knowledge is basic
      to the development of road tests and scoring procedures to evaluate the driving
      competence of older, experienced drivers, especially those whose fitness to drive
      may have been compromised by a medical illness that alters their mental
      abilities. We have drive tested over 100 currently driving elderly patients with
      clinically significant cognitive decline (mostly diagnosed as the early stages of
      Alzheimer disease) and compared their performance with that of normal drivers.
      The study identified the types of driving errors that distinguish and
      differentiate the cognitively impaired group as well as a set of driving errors
      typical of both cognitively impaired and normal experienced drivers but differing
      in the number and severity of errors. A set of errors was also identified that
      did not differentiate the groups and should not be used in evaluating a person's
      competence to drive.

PMID- 9194962
TI  - Environmental cueing may effect performance on a road test for drivers with
      dementia of the Alzheimer type.
AB  - This paper examines the impact of environmental cueing on a road test for persons
      with dementia of the Alzheimer type (DAT). In an earlier study, we demonstrated
      the reliability and stability of the Washington University Road Test in a sample
      of 58 healthy elderly controls and 65 subjects with DAT. We found that dementia
      adversely affects driving performance even in its mild stages. Here were
      elaborate on the results of a follow-up road test conducted 1 month after the
      baseline test (n = 63) explore possible reasons why the stability of the follow
      up road test was lower than expected. We conclude that environmental cueing may
      affect performance on a road test in DAT.

PMID- 9194963
TI  - Simulators for assessing driving skills in demented patients.
AB  - This paper reviews the appropriate use of simulators to assess driving abilities
      in individuals with dementing illnesses. Several points are addressed: What is a
      driving simulator? What are the characteristics of a simulator? What are the
      strengths and weaknesses of various types of simulators? The potential role of
      driving simulators for predicting future driving safety is discussed.

PMID- 9194964
TI  - Driving with Alzheimer disease: the anatomy of a crash.
AB  - Alzheimer disease (AD) affects several abilities that are crucial to automobile
      driving and can thereby increase the risk for a crash. The specific driver safety
      errors that lead up to crashes in this driver population, however, remain largely
      unknown. We developed a graphical means for dissecting these safety-related
      behaviors for application to car crashes of AD drivers. These crashes occurred in
      collision avoidance scenarios implemented on the Iowa Driving Simulator. Crash
      plots were produced by "rewinding" the data stream, then graphing the vehicle
      speed, path, steering wheel position, pedal positions, and driver gaze up to the
      very moment of impact. In this way, we were able to display in detail the
      patterns of vehicle and driver control to determine exactly how a crash occurred.
      Several different types of antecedent safety errors were noted, ranging from
      responding inappropriately with the hand and foot controls to not responding at
      all. In this paper we focus on the performance of a single impaired driver to
      demonstrate our technique and findings. Understanding the "anatomy" of crashes in
      cognitively disabled drivers with AD can help guide future efforts at injury
      prevention and control.

PMID- 9194965
TI  - Crashes: outcome of choice in assessing driver safety?

PMID- 9194966
TI  - Cognitive change, medical illness, and crash risk among older drivers: an
      epidemiological consideration.
AB  - This paper reviews selected issues concerning the natural history of cognitive
      change among older persons and whether the potential effects of such change on
      the safe operation of a motor vehicle can detected prior to the occurrence of an
      adverse outcome, such as a crash. Data are reviewed from selected recent, large,
      population-referent epidemiological studies that have sought direct associations
      between medical conditions of their treatments and crash risk. Several important
      medical risk factors have been identified and, if confirmed, these factors must
      be considered along with the assessment of cognitive decline and dementia when
      evaluating safety issues in older drivers.

PMID- 9194967
TI  - Motor vehicle crashes and drivers with DAT.
AB  - An increasing number of drivers with dementia is expected over the next few
      decades. From a public safety standpoint, there is concern that these drivers
      also will have an increased risk for motor vehicle crashes. This paper examines
      recent studies on motor vehicle crashes experienced by drivers with dementia
      and/or dementia of the Alzheimer type (DAT). These studies were analyzed for
      their common findings, strengths, and limitations. Many studies reveal an
      increased crash rate for drivers with DAT compared with nondemented older
      drivers. Studies suggest that 50% of DAT drivers stop driving within 3 years of
      the onset of disease, the risk for a motor vehicle crash increases with the
      duration of driving after disease onset, males are at increased risk for crashes,
      dementia severity does not correlate with risk for a crash, and additional
      medical conditions may further contribute to crash risk. Areas of focus for
      future studies in this field are discussed.

PMID- 9194968
TI  - Attentional problems and older drivers.
AB  - At a society level, there is a responsibility to meet the mobility needs of a
      growing population of older adults. Simultaneously, it is understood that some
      older adults will experience behavioral and/or physical changes that may preclude
      driving at some point in their lives. Because most older adults rely on the
      automobile to maintain their mobility and independence, there is sometimes
      reluctance to stop driving when impairments develop. Recent research has been
      aimed at finding ways to distinguish those drivers who may pose a threat to their
      own safety, as well as the safety of other road users, from the vast majority of
      competent drivers. These studies have indicated that measures of visual attention
      and cognitive function have been successful in distinguishing between these two
      groups. Finally, because visual attention skills can be improved with training,
      these findings have important implications for further evaluation of
      interventions to enhance the skills that underlie safe driving.

PMID- 9194969
TI  - The role of selective attention in driving and dementia of the Alzheimer type.
AB  - This paper examines the relationship between cognitive processes and driving in
      aging and dementia of the Alzheimer type. Several studies that have explored the
      relationship between neuropsychological test performance and various indicators
      of driving safety are reviewed. It is argued that deficits in selective attention
      are specific to impaired driving performance in dementia of the Alzheimer type.
      Results from a recent study supporting this notion are presented. It is suggested
      that screening measures that emphasize the ability to selectively attend to
      relevant information and inhibit irrelevant information should be used to
      identify mildly demented individuals who are at risk for unsafe driving.

PMID- 9194970
TI  - The demented driver: the doctor's dilemma.
AB  - Physicians play an important role in the driver licensing process because
      drivers, most frequently older ones, acquire diseases that impact their ability
      to operate a motor vehicle safely and because patients, their families, and
      regulatory agencies rely on them for diagnosis and treatment. It is now fairly
      clear that moderately and severely demented patients cannot drive safely.
      However, the issue of whether the mildly or very mildly demented patient can
      drive safely has not been fully resolved, although substantial evidence is
      emerging that most of these individuals have a higher accident risk than their
      healthier aged counterparts. Physicians, most commonly primary care physicians,
      will be encountering growing numbers of aged driving persons, particularly those
      over 70, who are at the greatest risk for developing age-related brain diseases
      in addition to other physical ailments. It is now evident that the cognitive
      impairment that accompanies these conditions can have a dramatic impact on
      driving ability, and recent legislation in a growing number of states (e.g.,
      California and Utah) requires physician reporting of cognitive impairment for
      driving purposes. Thus, what should the physician do with regard to the "at risk"
      older driver to ensure good medical practice while maintaining a sound ethical
      and legal posture toward the patient, his family, and the state and its agencies?
      This article reviews the status of physicians with regard to the cognitively
      impaired drivers, particularly in states where the law mandates reporting of such
      individuals. The problem of timely and effective screening for the cognitively
      impaired driver is raised, and alternative approaches to the screening process
      are discussed.

PMID- 9194971
TI  - The 1994 International Consensus Conference on Dementia and Driving: a brief
      report. Swedish National Road Administration.
AB  - A possible relationship exists between the increased relative crash risk of older
      drivers and the prevalence of age-related diseases such as dementia. However,
      although dementia effects cognitive functions essential for safe driving, the
      evaluation of driving competence in demented persons is problematic. A clear-cut
      policy, intended chiefly for primary care physicians, is still lacking. In
      recognition of this fact, the Swedish National Road Administration invited a
      group of researchers to review existing research and to formulate a consensus on
      the issue of driving and dementia. The consensus group suggested that physicians
      should routinely make a cursory evaluation of the mental condition of their older
      driving patients. When signs of cognitive impairment are detected, possible
      influence on visuospatial skills, attention, judgment, and memory functions
      should be carefully considered. Information from caregivers on past and current
      driving performance as well as functions relating to activities of daily living
      (ADL) should be taken into account. Consensus was reached that a diagnosis of
      moderate to severe dementia indicates sufficient cognitive impairment to preclude
      driving. In addition, diagnosed mildly demented individuals or nondiagnosed
      cognitively impaired individuals with functional deterioration should be
      considered for specialized assessment of driving competence.

PMID- 9194972
TI  - Predicting and coping with the consequences of stopping driving.

PMID- 9194973
TI  - Strategies for driving cessation in Alzheimer Disease.

PMID- 9194974
TI  - Safe mobility for people with Alzheimer disease: a commentary.

PMID- 9194975
TI  - Automobile insurance and the mentally impaired driver.

PMID- 9194976
TI  - Concerned Americans for responsible driving (CARD): a personal narrative.

PMID- 9194978
TI  - Consumers receive written information with most prescriptions, report indicates.

PMID- 9194977
TI  - FDA cites new data in decision to bar generic conjugated estrogens.

PMID- 9194979
TI  - Community pharmacists' interventions may reduce health care costs.

PMID- 9194980
TI  - Gastroenterologists issue guidelines on ulcerative colitis management.

PMID- 9194981
TI  - HMO utilization found similar between enrollees with and without prior health
      insurance.

PMID- 9194982
TI  - Involving anesthesiology in drug control.

PMID- 9194983
TI  - Adverse events and cost savings three years after implementation of guidelines
      for outpatient contrast-agent use.
AB  - The ability of guidelines limiting the use of low-osmolality contrast media
      (LOCM) to save money without jeopardizing patient care was studies. In February
      1993 an academic medical center implemented guidelines to reduce the use of LOCM
      for outpatient computed tomography and excretory urography; the guidelines
      limited LOCM to patients at high risk of adverse reactions to contrast agents.
      Data on contrast media received and frequency of adverse events were compiled
      from billing sheets and incident reports for March 1993 through February 1996.
      The number of patients receiving LOCM over the three years was 1325, and the
      number receiving high-osmolality contrast media (HOCM) was 4435. Of the HOCM
      recipients, 165 (3.7%) had adverse reactions; 0.4% of these reactions were major,
      3.1% were minor, and 0.2% were extravasations. Among LOCM-treated patients, 35
      (2.7%) had adverse reactions; 0.5% were major, 1.7% were minor, and 0.5% were
      extravasations. The only significant difference in adverse effects between the
      groups was in the frequency of minor reactions. The costs of HOCM and LOCM over
      the three years were $54,660 and $152,523, respectively. Had 90% of the 5760
      patients received LOCM, the total cost of contrast agents would have been
      $603,723; thus, the estimated drug cost saving was $396,540, or $132,180
      annually. With costs of treating adverse events factored in, the net annual cost
      saving was $132,093. Guidelines limiting the use of LOCM to high-risk patients
      saved an academic medical center an estimated $132,093 annually in drug costs for
      specific outpatient imaging procedures, without adversely affecting patient care.

PMID- 9194984
TI  - Stability of ursodiol 25 mg/mL in an extemporaneously prepared oral liquid.
AB  - The stability of ursodiol in an extemporaneously formulated oral liquid was
      studied. A suspension was prepared by combining the contents of commercially
      available 300-mg capsules of ursodiol with glycerin, Ora-Plus (Paddock
      Laboratories), and orange syrup. A second formulation was prepared by combining
      ursodiol capsules with sterile water for irrigation. The final concentration of
      ursodiol in each formulation was 25 mg/mL. Six samples of each preparation were
      stored in 4-oz amber plastic prescription bottles protected from light. Three
      were stored at 22-23 degrees C and three were refrigerated at 2-6 degrees C.
      Immediately after preparation and at 7, 15, 30, 45, and 60 days, samples were
      obtained and frozen until assay by high-performance liquid chromatography. On day
      60 the mean percentage of the initial ursodiol concentration remaining was 108.4%
      for the suspension stored at room temperature and 103.3% for the refrigerated
      suspension. The ursodiolin-water formulation was not analyzed because of rapid
      settling of ursodiol. Ursodiol 25 mg/mL in an oral liquid prepared
      extemporaneously from capsules and sweetened vehicle was stable for 60 days when
      stored in amber plastic bottles at 22-23 and 2-6 degrees C. Addition of ursodiol
      powder to water without a suspending agent resulted in a liquid formulation with
      a high variability in content uniformity.

PMID- 9194985
TI  - Stability of granisetron hydrochloride in an extemporaneously prepared oral
      liquid.
AB  - The stability of granisetron 0.2 mg/mL (as the hydrochloride salt) in an
      extemporaneously prepared oral liquid was studied. Twelve 1-mg granisetron
      tablets were pulverized and suspended in 30 mL of distilled water. This mixture
      was then diluted with cherry syrup to produce a 60-mL oral liquid with a
      granisetron concentration of 0.2 mg/mL. Half of the preparation was stored at 5
      degrees C, and half was stored at 24 degrees C. Samples were taken on days 0, 1,
      2, 3, 4, 6, 8, 10, 12, and 14 and assayed by high-performance liquid
      chromatography. There was no change in the liquid's color, consistency, or pH,
      and the concentrations of granisetron ranged from 97% to 104% of initial
      concentration during the 14 days at 5 and 24 degrees C. Granisetron 0.2 mg/mL (as
      the hydrochloride salt) in an extemporaneously prepared oral liquid was stable
      for up to 14 days.

PMID- 9194986
TI  - Continuity of pharmaceutical services for patients with AIDS in the transition
      from hospital to home.

PMID- 9194987
TI  - Practical, ongoing competency-assessment program for hospital pharmacists and
      technicians.

PMID- 9194988
TI  - Stability of high-concentration dopamine hydrochloride, norepinephrine
      bitartrate, epinephrine hydrochloride, and nitroglycerin in 5% dextrose
      injection.

PMID- 9194989
TI  - Mechanisms of bacterial resistance to antimicrobial agents.
AB  - The mechanisms behind the development and spread of bacterial resistance to
      antimicrobial drugs are reviewed. The chief mechanisms by which antimicrobials
      act are interference with nucleic acid synthesis, binding to ribosomes, and
      inhibition of cell-wall synthesis and folate metabolism. Bacteria have evolved
      genetic and biochemical ways of resisting these antimicrobial actions. Genetic
      mechanisms include mutation and acquisition of new DNA. Bacteria resist
      antimicrobials biochemically by inactivating the drugs with beta-lactamases,
      acetylases, adenylases, and phosphorylases; reducing drug access sites of action
      by virtue of membrane characteristics; altering the drug target so that the
      antimicrobial no longer binds to it; bypassing the drug's metabolism; and
      developing tolerance. Enterococcal and staphylococcal resistance mechanisms are
      of particular importance clinically. There are three types of enterococcal
      resistance: (1) intrinsic resistance to aminoglycosides, aztreonam,
      cephalosporins, clindamycin, imipenem, penicillin, and trimethoprim
      sulfamethoxazole, (2) tolerance to all cell-wall-active antimicrobials, and (3)
      acquired resistance to penicillin, aminoglycosides, chloramphenicol,
      erythromycin, tetracycline, and vancomycin. Staphylococcal resistance to
      penicillins is expressed as beta-lactamase production, secretion of novel beta
      lactamases, expression of novel penicillin-binding proteins (PBPs) to which
      penicillins bind poorly, and increased production of or altered affinity to
      existing PBPs. Of great concern is whether newly described glycopeptide
      resistance can be transferred clinically from enterococci to staphylococci.
      Vancomycin use is discouraged to limit the spread of glycopeptide resistance.
      Many mechanisms are responsible for the development and spread of antimicrobial
      resistance.

PMID- 9194990
TI  - Improving the quality of outcomes research involving pharmaceutical services.

PMID- 9194991
TI  - Facilitating emergency use of alteplase for stroke.

PMID- 9194992
TI  - Precipitation of amphotericin B from i.v. fat emulsion.

PMID- 9194994
TI  - Useful Internet sites.

PMID- 9194993
TI  - Medication errors and drug hydrates.

PMID- 9194995
TI  - Reappraisal of indispensable amino acids. Design of parenteral synthetic
      dipeptides: synthesis and characterization.

PMID- 9194996
TI  - Design of parenteral synthetic dipeptides for clinical nutrition: in vitro and in
      vivo utilization.

PMID- 9194997
TI  - Impedance ratio as a measure of water shifts.
AB  - Total and segmental body compositions (left arm and left leg) were measured by
      bioelectrical impedance analysis at 5 and 100 kHz and by dual-energy X-ray
      absorptiometry (DXA) in 14 healthy young males (body mass index, mean +/- SD,
      23.5 +/- 2.7 kg/m2) every 20 min for a period of 100 min. During the measurements
      the subjects remained in the supine position on the examination table, except for
      the time between the last two measurements, where they got up to walk around.
      This study focuses on the impact of orthostatic fluid shifts on impedance ratios
      in body segments and the total body. After 20 min of lying supine lean tissue
      (DXA) was slightly but significantly lower for the total body and the left leg,
      but all other consecutive DXA measurements at different times did not differ.
      Total body impedance and leg impedance increased during the time the subjects
      were in the recumbent position. Impedance changes in the leg were more pronounced
      than in the total body, and at 5 kHz the changes were more pronounced compared to
      100 kHz. After the subjects got up the impedance values again decreased.
      Impedance ratios (Z5/Z100) increased for both the leg and to a lesser extent for
      the total body during the time lying supine, but again decreased after getting
      up. The results of this study indicate a fluid shift from the legs to the trunk
      after lying supine and show that this fluid shift is mainly extracellular water.
      DXA measurements were not able to detect these changes, probably because the
      magnitude of these changes is below the detection level for lean tissue with DXA
      methodology. The observations have important implications in the interpretation
      of impedance measurements in the clinical situation when measurements are made in
      patients who have been reclining for some time.

PMID- 9194999
TI  - Dietary underreporting: validity of dietary measurements of energy intake using a
      7-day dietary record and a diet history in non-obese subjects.
AB  - Substantial dietary underreporting questions the validity of dietary measurements
      of energy intake (EI). The present study compares the value of a 7-day
      prospective dietary record (7dDR) with a computer program-based diet history
      (DH). 7dDR and DH were performed in 50 non-obese subjects (33 females, 17 males,
      mean age 26.1 years, BMI 18.9-29.6 kg/m2) using total energy expenditure (EE =
      sum of resting metabolic rate as measured by indirect calorimetry plus energy
      expenditure derived from an activity protocol) as standard for the validity of
      data on EI. EI was 2,206 (728-3,646) kcal/day for 7dDR and 2,398 (566-4,764)
      kcal/day for DH. There was an association between EI for 7dDR and EI for DH (r =
      0.6, p < 0.0001). Underreporting [i.e. a difference between EI and EE (delta E =
      EI - EE)] of 20% or more was seen in 48% (7dDR, mean -1,047 kcal/day, range -616
      to -1,895, or -38.8% of EE) or 48% (DH, -1,151 kcal/day, -594 to -2,057 kcal/day,
      or -42.3% of EE). Considerable differences were found between delta E for 7dDR
      and delta E for DH (mean 603, range 26-2,033 kcal/day), and only 34% of
      underreporting subjects were identified by both dietary measurements. It is
      concluded that at the individual level dietary underreporting is influenced by
      the dietary assessment tool.

PMID- 9194998
TI  - Coffee consumption and total body water homeostasis as measured by fluid balance
      and bioelectrical impedance analysis.
AB  - To investigate the impact of coffee consumption on fluid balance, 12 healthy
      volunteers were supplied with a standardized diet for 2 days after having
      abstained from consumption of methylxanthines for 5 days. During the first day,
      fluid requirement was met by mineral water. On the following day the same amount
      of fluid was supplied and the mineral water was in part replaced by 6 cups of
      coffee containing 642 mg of caffeine. This led to an increase in 24-hour urine
      excretion of 753 +/- 532 ml (p < 0.001), a corresponding negative fluid balance
      and a concomitant decrease in body weight of 0.7 +/- 0.4 kg (p < 0.001). Total
      body water as measured with bioelectrical impedance analysis decreased by 1.1 +/-
      1.2 kg or 2.7% (p < 0.01). Urinary excretion of sodium and potassium was elevated
      by 80 +/- 62 mmol or 66% (p < 0.01) and 14 +/- 12 mmol or 28% (p < 0.01),
      respectively.

PMID- 9195000
TI  - Bile acid metabolism by colonic bacteria in continuous culture: effects of starch
      and pH.
AB  - Secondary bile acids (BA) have been shown to be involved as a promoting agent in
      the adenoma-carcinoma sequence of colorectal cancer. In previous studies,
      fermentation of starch has been shown to inhibit the degradation of primary to
      secondary BA by the colonic microflora. This study was designed to investigate BA
      metabolism in continuous cultures of mixed fecal bacteria to get further insights
      into the mechanisms of this inhibition. Fermentation vessels were fed with media
      containing cholic (0.6 g/l) and chenodeoxycholic acid (0.4 g/l). Cultures were
      either starch-free or enriched with starch (10 g/l). pH was controlled and
      adjusted to 7.0 or 6.0. Total culture duration was 28 days and concentrations of
      BA, short-chain fatty acids (SCFA), and starch were measured periodically. At pH
      6, significantly more primary BA remained in the media and less secondary BA were
      produced. Total BA concentrations were lower at pH7. SCFA concentrations were
      higher in the vessels supplemented with starch. Starch was completely fermented
      and not present in significant amounts in any fermentation vial after the first
      week. These data indicate that bacterial breakdown of primary to secondary BA is
      inhibited when starch is simultaneously fermented. This effect can be explained
      by the reduction of pH resulting from SCFA production. Considering these
      findings, resistant starch which escapes assimilation in the small bowel may be a
      protective factor against colorectal cancer.

PMID- 9195001
TI  - Effects of protein-energy malnutrition on muscarinic receptor density and
      acetylcholinesterase activity in rat brain.
AB  - The effect of protein-energy malnutrition on the muscarinic receptor density as
      indicated by 3H-N-methylscopolamine binding, and acetylcholinesterase activity
      was studied in several brain areas (hippocampus, motor area, somatosensory area,
      and basal ganglia) of adult female rats. Malnutrition tended to cause a decrease
      in muscarinic receptors in the motor cortex (undernourished 350.0 +/- 33.5 vs.
      control 410.0 +/- 26.9 fmol/mg protein) and somatosensory cortex (undernourished
      357.1 +/- 35.9 vs. control 416.7 +/- 29.4 fmol/mg protein). However, significant
      decreases in muscarinic receptor occurred in the hippocampus (undernourished
      319.2 +/- 31.7 vs. control 403.1 +/- 43.6 fmol/mg protein) and basal ganglia
      (undernourished 297.0 +/- 11.8 vs. control 401.3 +/- 17.7 fmol/mg protein). No
      significant differences in acetylcholinesterase activity or protein content were
      observed between control and undernourished animals in any of the brain areas
      studied.

PMID- 9195002
TI  - Postnatal caffeine effects on copper, zinc, and iron concentrations in mammary
      gland, milk, and plasma of lactating dams and their offspring.
AB  - Beginning on the day of delivery and until the 15th or 22nd day of lactation, one
      group of dams received a 20% protein diet as a basal diet and one group received
      the basal diet supplemented with caffeine (4 mg/100 g body weight). A correlation
      between caffeine concentrations in the dams' plasma and milk was observed. In the
      caffeine group, levels of Fe and Cu in the dams' mammary glands at day 22 were
      decreased. Copper levels in the milk at day 15 and Fe and Zn levels in the milk
      at day 22 showed a significant decrease. Copper concentration in the plasma of 15
      day-old pups showed a significant decrease also, but Zn and Fe concentration
      showed no difference between caffeine and noncaffeine control groups. The present
      study shows that the dams' consumption of a caffeine-containing diet influences
      trace elements of mammary glands, milk, and pups' plasma.

PMID- 9195003
TI  - Medical education in nutrition in Europe. Workshop.

PMID- 9195004
TI  - Hormonema schizolunatum, a new species of dothideaceous black yeasts from
      phyllosphere.
AB  - Two black yeast isolates from plants from the Canary Islands (Spain) are
      described and illustrated. Absence of Woronin bodies at simple septal pores,
      local coralloid terminal hyphal cells, indeterminate thallus maturation, the
      presence of budding cells and local conversion to meristematic growth all
      indicate a relationship to the Dothideaceae (Dothideales, Ascomycota).
      Morphological properties were consistent with the genus Hormonema Lagerberg &
      Melin, as defined by presence of percurrent conidiogenous loci alongside
      undifferentiated hyphae, and results of PCR-ribotyping supported this
      classification. The isolates were judged to belong to a hitherto undescribed
      species, characterized in particular by curved conidia soon developing transverse
      septa. The physiological profile of this species is also described.

PMID- 9195005
TI  - Taxonomic description of Methanococcoides euhalobius and its transfer to the
      Methanohalophilus genus.
AB  - A sequence analysis of the 16S-rRNA of Methanococcoides euhalobius revealed that
      this organism was highly related to members of the genus Methanohalophilus. On
      the basis of sequence data, an oligonucleotide probe specific to
      Methanohalophilus species was designed. Hybridization studies with this probe
      confirmed close relationship of Methanococcoides euhalobius to Methanohalophilus
      species. Therefore, we propose that Methanococcoides euhalobius should be
      transferred to the genus Methanohalophilus as Methanohalophilus euhalobius.

PMID- 9195006
TI  - Laboratory screening of different Bacillus thuringiensis strains against certain
      lepidopteran pests and subsequent field evaluation on the pod boring pest complex
      of pigeonpea (Cajanus cajan).
AB  - Laboratory evaluation of different Bacillus thuringiensis subspecies revealed
      that B. thuringiensis subsp. kurstaki (NCIM 2514) at 10(8) spores/ml
      concentration caused more than 85% mortality to the neonate larvae of the
      lepidopteran insects Spodoptera litura (F.) and Phthorimaea operculella (Z.).
      This strain at 10(10) spores/ml concentration was effective against the major
      lepidopteran pests comprising the pod boring complex of pigeonpea (Cajanus
      cajan), viz. Helicoverpa armigera (H.) and Exelastia atomosa (W.) under the field
      trials. Total grain yield from this treatment was least 1.5 times more than the
      untreated control.

PMID- 9195007
TI  - Lipomyces mesembrius sp. nov., a member of the L. starkeyi species-complex.
AB  - Lipomyces starkeyi is known to be associated with three strains-clusters showing
      high mutual nDNA reassociation within each cluster, but which reassociate
      ambiguously with the type of L. starkeyi. Representative strains of L. starkeyi
      and Cluster alpha were examined for possible genetic exchange by the prototrophic
      selection technique. Since no genetic recombination was detected, the strains are
      presumed to be genetically isolated. Cluster alpha is consequently assigned to
      the rank of species as Lipomyces mesembrius. A description of the new species is
      given. Lipomyces kononenkoae ssp. spencermartinsiae has been raised to the rank
      of species as L. spencermartinsiae.

PMID- 9195008
TI  - Phylogenetic and physiological comparisons of PAH-degrading bacteria from
      geographically diverse soils.
AB  - The diversity of bacteria isolated from creosote- contaminated soils in the
      United States, Norway, and Germany was determined by comparing their ability to
      degrade polycyclic aromatic hydrocarbons (PAHs), their phospholipid ester-linked
      fatty acid (GC-FAME) profiles, sole carbon source utilization patterns (Biolog
      assays), and 16S rRNA sequences. Bacteria were initially obtained by enrichment
      with phenanthrene and fluoranthene. Many were capable of degrading a broad range
      of the PAHs found in creosote. Phenanthrene- or fluoranthene-degraders were
      abundant in most of the soils tested. Several of the fluoranthene-degrading
      isolates clustered with Sphingomonas (formerly Pseudomonas) paucimobilis strain
      EPA505 in the GC-FAME and Biolog analyses and three of the isolates examined by
      16S rRNA sequence comparisons showed a close relationship with Sphingomonas. In
      addition, the Sphingomonas strains showed the most extensive degradation of 4- &
      5-ring PAHs in creosote. Burkholderia cepacia strains isolated on phenanthrene
      from PAH-contaminated soils had limited ability to attack higher molecular weight
      PAHs either individually or in creosote. Thus, degradation capabilities appeared
      to be associated with members of certain taxa, independent of the origin of the
      soils from which the bacteria were isolated.

PMID- 9195009
TI  - Physiological characterization of a microbial sensor containing the yeast Arxula
      adeninivorans LS3.
AB  - The yeast Arxula adeninivorans LS3 is a suitable organism for use as part of a
      microbial sensor. In combination with an amperometric oxygen electrode the sensor
      offered a possibility for the physiological characterization of this yeast. About
      300-400 measurements could be carried out with a single Arxula sensor. The
      microbial sensor was remarkably stable for over 35 days, when kept at 37 degrees
      C during the operation time and at room temperature overnight. The physiological
      characteristics of Arxula adeninivorans LS3 obtained with the sensor technique
      were identical to the data obtained with the conventional techniques. However,
      the sensor technique makes it additionally possible to quantify the physiological
      data. So the substrates ribose, citric acid, glycerol, oil and benzoate produced
      signals lower than 10% in comparison to the glucose signal. Fructose, xylose,
      sucrose, maltose, gentianose, glucosamine, glutamic acid, tryptophan, butyric
      acid, lauryl acid and propionic acid reached 10-70%, galactose, alanine, glycine,
      lysine and methionine signals were similar to the glucose signal whereas acetic
      acid, ethyl alcohol, capron acid, capryl acid and caproic acid reached the
      highest signals up to 434%.

PMID- 9195010
TI  - Regulation of ammonia assimilation in an obligate methylotroph Methylobacillus
      flagellatum under steady-state and transient growth conditions.
AB  - The obligate methylotroph Methylobacillus flagellatum was grown in the presence
      of different ammonium concentrations and the regulation of the enzymes associated
      with ammonium assimilation was investigated in steady-state and transient growth
      regimes. As the medium changed from C-limitation to dual C/N- and finally to N
      limitation, the culture passed through three definite growth phases. The NADP(+)
      dependent glutamate dehydrogenase (GDH) was present under ammonium limitation of
      the culture growth (at 2 mmol 1(-1) of ammonium in the growth medium) and
      increased in response to an increase in nitrogen availability. Glutamine
      synthetase (GS) and glutamate synthase (GOGAT) activities were negligible during
      C- and C/N-limitation. In N-limited cells the GOGAT activity increased as the
      dilution rate increased up to 0.35 h-1, and then sharply dropped. In the N
      sufficient cultures both NAD(+)-and NADP(+)-dependent isocitrate dehydrogenase
      (NAD-ICDH and NADP-ICDH) activities were up-regulated as dilution rate increased,
      but in the N-limited culture the NAD-ICDH activity was up-regulated whereas NADP
      ICDH one was down-regulated. Pulse additions of ammonium and methanol
      demonstrated the coordinate regulation of the GDH and ICDHs activities. When
      pulses were added to the C/N-limited cultures, there was an immediate utilization
      of the nutrients, resulting in an increase in biomass; at the same time the GDH
      and ICDH activities increased and the GS and GOGAT activities decreased. When the
      same ammonium/methanol pulse was added into the N-limited culture, there was a 3
      h delay in the culture response, after which the substrates were utilized at
      rates close to the ones shown by the C/N-limited culture after the analogous
      pulse.

PMID- 9195011
TI  - Molecular evolution in bacteria: surfaces, cathodes and anodes.
AB  - Molecular evolution is examined in bacteria with an emphasis on mineral surfaces,
      membranes, cathodes and anodes. In early molecular evolution, cathode-anode
      system may have been naturally occurring on a nm to micron scale. Secondly, the
      cathode-anode system could have been separated by a primitive, permeable lipid or
      microsphere on a mineral surface, that was a precursor of a more advanced
      membrane with a charge differential on either side of the membrane. These aspects
      will be considered from a theoretical evolutionary perspective.

PMID- 9195012
TI  - Changes in the starvation response through covalent cell attachment.
AB  - Covalent attachment of Candida utilis cells, possibly simulating natural
      microbial immobilizations, stimulated stable and significant enhancement of
      extracellular production of alkaline protease, specifically induced by four
      different starvation conditions. The enzyme analysis confirmed the identity of
      the proteases released under all conditions of starvation and no parallel
      production of other proteolytic enzyme. The enhancement phenomenon as a uniform
      and stable effect of the whole cell immobilization is discussed in relation to
      the effect of multipoint, cell-solid surface contact, potentially bringing
      positive modulations of complex, cellular functions.

PMID- 9195013
TI  - Candida novakii, sp. nov. a new anamorphic yeast species of ascomycetous
      affinity.
AB  - Two strains of an undescribed species of the genus Candida were isolated from
      decaying wood of Quercus sp. A description of the new species Candida novakii is
      given.

PMID- 9195014
TI  - The potential of mining slag as a substrate for microbial growth and the
      microbiological analysis of slag and slag seepage.
AB  - The potential of a Cu/Ni mining slag to act as a substrate for the growth of the
      bacteria Thiobacillus ferrooxidans, Thiobacillus thiooxidants, and Thiobacillus
      thioparus was examined. As well, slag and slag seepage samples were screened for
      the presence of the Thiobacillus species. For the 28 samples employed in the
      environmental recovery studies, T. ferrooxidans was recovered in 25 samples, T.
      thiooxidans in 19 samples, and T. thioparus in 27 samples. For R. ferrooxidans,
      the development of a colour change in the medium corresponded with the presence
      of motile bacilli as detected microscopically. For T. thiooxidans and T.
      thioparus, a decrease in culture pH of greater than 0.2 units usually
      corresponded with the presence of motile bacilli. The potential for growth on
      slag was determined by adding slag samples to media (devoid of an electron donor)
      appropriate for the growth of the three Thiobacillus species. All pulverized slag
      samples supported the growth of the three species.

PMID- 9195015
TI  - Protective effect of deferoxamine on chromium (VI)-induced DNA single-strand
      breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat
      hepatocytes.
AB  - Incubation of primary cultures of rat hepatocytes with K2CR2O7 and deferoxamine
      (DFO), an iron chelator, resulted in a marked decrease in cellular levels of DNA
      single-strand breaks caused by K2Cr2O7. Cellular treatment with DFO also
      suppressed both dichromate-induced cytotoxicity--evaluated by the leakage of
      lactate dehydrogenase, and lipid peroxidation--as monitored by malondialdehyde
      formation. In addition, treatment with DFO attenuated the suppression of the
      levels of vitamin E and C as well as the inhibition of alkaline phosphatase and
      glutathione peroxidase activity attributed to K2Cr2O7. However, DFO had no
      influence on the cellular level of glutathione or the activity of glutathione
      reductase and superoxide dismutase suppressed by dichromate. Under the same
      experimental conditions, cellular uptake and distribution of chromium were not
      affected by DFO. These results indicate that DFO protects cells from chromium
      (VI)-induced DNA strand breaks, cytotoxicity, lipid peroxidation, vitamin E and C
      depression, and glutathione peroxidase inhibition The role of antioxidants in
      chromium (VI)-induced cytotoxicity, DNA breaks, and lipid peroxidation is
      discussed.

PMID- 9195016
TI  - Quantitation of alpha(2)-microglobulin after administration of structurally
      divergent chemical compounds.
AB  - alpha(2)-Microglobulin-induced nephropathy is a phenomenon which is exclusively
      found in adult male rats. Various chemicals are able to bind to alpha(2)
      microglobulin thus inhibiting its proteolytic degradation in lysosomes of the P2
      segment of the rat nephron. The accumulation of this protein in 'protein
      droplets' or 'hyaline droplets' leads to necrosis, followed by regeneration which
      possibly later results in the formation of tumours. Here we report the
      development of a monoclonal antibody which is specific for alpha(2)
      microglobulin. It was utilized to measure alpha(2)-microglobulin concentrations
      in plasma and tissues, and to stain alpha(2)-microglobulin in fixed tissue
      slides. In two studies we administered to adult male Wistar rats two groups of
      compounds: (1) one group of structurally diverse compounds, which give an
      overview of chemical entities capable of inducing the accumulation of alpha(2)
      microglobulin; and (2) another group of structurally closely related compounds
      (i.e. substituted benzene derivatives) for the purpose of elucidating possible
      structure-activity relationships. The degree of alpha(2)-microglobulin-induced
      nephropathy was determined by immunohistochemical staining of kidney sections. In
      addition, liver and kidney tissue and plasma concentrations of alpha(2)
      microglobulin were not found to be elevated whereas kidney tissue concentrations
      were higher than the controls. The increase over control values ranged from 154%
      (1,4-dichloromethyl-benzene) to 321% [alpha-methyl-4-(1-methylethyl)
      cyclohexanemethanol]. Comparing structurally related benzene derivatives, the
      hyaline droplet accumulating (HDA) potential was found to depend both on the type
      of substituent and its position at the aromatic ring. In general HDA activity
      increased in the order benzene approximately equal to phenol approximately equal
      to alkylated phenols < halogenated phenols < halogenated benzenes. Further QSAR
      studies are needed to provide a theoretical base for these observations.

PMID- 9195017
TI  - Toxicity and cytotoxicity of nigrin b, a two-chain ribosome-inactivating protein
      from Sambucus nigra: comparison with ricin.
AB  - Nigrin b, a lectin isolated from the bark of elderberry (Sambucus nigra L.), has
      structure and enzymatic activity similar to that of ricin and other type 2
      ribosome inactivating proteins (RIPs), and yet is much less toxic to cells and
      animals. In an attempt to explain this difference, we studied (1) the
      cytotoxicity of both lectins at 18 and 37 degrees C, and in the presence of
      substances interfering with intracellular routing, and (2) the binding of nigrin
      b to, and its uptake and degradation by HeLa cells, in parallel with ricin. As
      compared with the latter, (1) less nigrin b was bound and more was degraded by
      cells, with a resulting lower concentration remaining inside the cells, and (2)
      there is evidence for a different intracellular routing followed by the two
      lectins. These results may explain at least partly the different cytotoxicity and
      consequently the lower toxicity to mice of nigrin b compared with ricin.

PMID- 9195018
TI  - Induction of micronuclei with ochratoxin A in ovine seminal vesicle cell
      cultures.
AB  - The genotoxic potential of the carcinogenic mycotoxin of ochratoxin A (OTA) has
      been investigated by means of an in vitro micronucleus assay, an endpoint for
      genotoxicity which has not been studied previously for OTA. OTA was found to
      induce dose-dependently micronuclei (MN) in cytokinesis-blocked binucleated ovine
      seminal vesicle (OSV) cell cultures, which had been treated with mycotoxin (12-30
      microM) for 6 h in medium containing 10% fetal calf serum. For comparison, OSV
      cells were treated with colcemid (0.02-0.06 micrograms/ml), or 4-nitroquinoline N
      oxide (NQO; 0.5 microM), a typical aneugen and clastogen, respectively. All test
      compounds increased the frequency of MN in OSV cells, the highest level being
      induced by 10 microM OTA. When MN were characterized by indirect
      immunofluorescence microscopy using anti-kinetochore (CREST) antibodies, the
      majority of MN in colcemid-treated cells was CREST-reactive (> 70% kinetochore
      positive); as expected, this fraction was < 10% for the NQO-treatment group. In
      cells treated with OTA the fraction of kinetochore positive MN was similar (33
      40%) to that observed in solvent controls (38%). These data indicate that OTA
      induces MN apparently by a mixed, although predominantly clastogenic mode of
      action. OSV cells lack monooxygenase activity but express high prostaglandin H
      synthase (PGHS) activity. When cells were treated with OTA in the presence of
      indomethacin (10 and 10 microM), a well known inhibitor of PGHS, the frequency of
      MN induced by OTA was not decreased, but rather increased. This indicates that
      metabolic activation of OTA by PGHS seems not to be required for genotoxicity.
      The increased MN induction in OSV cell cultures is most likely due to competition
      in indomethacin with OTA for binding to serum proteins thus raising the fraction
      of free mycotoxin.

PMID- 9195019
TI  - Effect of subchronic 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on immune
      system and target gene responses in mice: calculation of benchmark doses for
      CYP1A1 and CYP1A2 related enzyme activities.
AB  - The dose-effect relationships were analysed for several noncarcinogenic
      endpoints, such as immunological and biochemical responses at subchronic, low
      dose exposure of female C57BL/6 mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD). The animals were treated i.p. with TCDD according to the initial- and
      maintenance-dose principal for a period of 135 days. The initial doses were 1, 10
      and 100 ng TCDD/kg, the weekly maintenance doses were 0.2, 2 and 20 ng TCDD/kg,
      respectively. At days 23, 79 and 135 of TCDD/kg, treatment 10 animals of each
      dose group were killed. As immunological parameters the number of thymocytes and
      the pattern of thymocyte subpopulations were determined. In liver, lung and
      thymus, mRNA expression of TGF-alpha, TGF-beta(1), TGF-beta(2), TGF-beta(3), TNF
      alpha, IL-1 beta and different CYP1 isoforms (CYP1A1, CYP1A2, CYP1B1) was
      analysed. In the livers, activities of 7-ethoxyresorufin-O-deethylase (EROD) and
      7-methoxyresorufin-O-demethylase (MROD) were measured. TCDD content in the liver
      was determined. The main results are summarized as follows: (1) The TCDD doses
      were not sufficient to elicit dose-dependent changes of pattern of thymocyte
      subpopulation. (2) TCDD failed to change the mRNA expression of TGF-alpha, TGF
      beta and TNF-alpha, but led to an increase of IL-1 beta mRNA expression in liver,
      lung and thymus. The results show that the TCDD induced IL-1 beta mRNA increase
      is at least as sensitive a marker as the induction of CYP1A isoforms. (3) The
      expression of CYP1B1 mRNA remained unchanged at the doses tested, while CYP1A1
      and CYP1A2 mRNA expression was dose-dependently enhanced. EROD and MROD
      activities in the liver paralleled the increases of CYP1A1 and CYP1A2 mRNA
      expression. (4) Regression analysis of the data showed that most of the
      parameters tested fit a linear model. (5) From the data, a benchmark dose for
      EROD/MROD activities in the livers of female C57BL/6 mice of about 0.03 ng
      TCDD/kg per day was calculated.

PMID- 9195020
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in infants. A
      toxicokinetic model of human lifetime body burden by TCDD with special emphasis
      on its uptake by nutrition.
AB  - Contents of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of 16 further
      congeners--polychlorinated dibenzodioxins and dibenzofuranes (PCDD/PCDF)--were
      determined in lipids of adipose tissue and of livers of 3 stillborns and of 17
      infants (0.43-44 weeks old) who died from sudden infant death syndrome.
      International toxic equivalents (I-TEq) calculated for the sum of TCDD together
      with all of the 16 congeners (1.55-29.63 ng/kg lipids of adipose tissue, n = 20;
      2.05-57.73 ng/kg liver lipids, n = 19) were within the range of or lower than the
      values published for adults. TCDD concentrations in lipids of breast-fed infants
      were higher (0.38-4.1 ng/kg lipids of adipose tissue, n = 9; 0.49-3.9 ng/kg liver
      lipids, n = 8) compared to non breast-fed subjects (0.16-0.76 ng/kg lipids of
      adipose tissue, n = 8; 0.29-0.71 ng/kg liver lipids, n = 7). Neither I-TEq values
      nor TCDD concentrations exceeded values published for adults. Since even in
      stillborns PCDD/PCPF were found (I-TEq, 9.70-10.83 ng/kg lipids of adipose
      tissue, 6.17-8.83 ng/kg liver lipids; TCDD, 1.3-2.1 ng/kg lipids of adipose
      tissue, 0.76-1.5 ng/kg liver lipids; n = 3), transplacental exposure has to be
      deduced. All of the findings concerning TCDD concentrations in the organism
      become intelligible on the basis of a physiological toxicokinetic model which was
      developed to describe the body burden of TCDD for the entire human lifetime in
      dependence of TCDD uptake from contaminated nutrition. The model reflects sex and
      age dependent changes in the following parameters: body weight, volumes of liver,
      adipose and muscle tissue, food consumption, and excretion of faeces. TCDD is
      supposed to be taken up orally, to be distributed freely in lipids of the
      organism and to be eliminated unchanged by excretion in lipids of faeces as well
      as by metabolism in the liver. The model was used to predict the half-life of
      elimination of TCDD (4 months in newborns increasing to approximately 5 years in
      adults) and concentrations of this compound in lipids of adipose tissue, blood,
      liver and faeces at different ages. Furthermore, the influence of breast-feeding
      on the TCDD burden of a mother, her milk and her child was simulated. The model
      was validated by means of own data gained in adipose tissue and livers of infants
      and also using a series of values measured by other authors in mother's milk and
      in tissues and faeces of infants and adults. Predictions as well as experimental
      findings demonstrate a distinct increase in the TCDD body burden of breast-fed
      infants. Generally, it can be concluded for the excretion of unchanged, non
      volatile, non protein bound highly lipophilic compounds that their half-life is
      short in infants (approximately 5 months) and increases to approximately 10 years
      reached between 40 and 60 years of age.

PMID- 9195021
TI  - Cytochrome P450-dependent drug oxidation activities in liver microsomes of
      various animal species including rats, guinea pigs, dogs, monkeys, and humans.
AB  - Levels of cytochrome P450 (P450 or CYP) proteins immunoreactive to antibodies
      raised against human CYP1A2, 2A6, 2C9, 2E1, and 3A4, monkey CYP2B17, and rat
      CYP2D1 were determined in liver microsomes of rats, guinea pigs, dogs, monkeys,
      and humans. We also examined several drug oxidation activities catalyzed by liver
      microsomes of these animal species using eleven P450 substrates such as
      phenacetin, coumarin, pentoxyresorufin, phenytoin, S-mephenytoin, bufuralol,
      aniline, benzphetamine, ethylmorphine, erythromycin, and nifedipine; the
      activities were compared with the levels of individual P450 enzymes. Monkey liver
      P450 proteins were found to have relatively similar immunochemical properties by
      immunoblotting analysis to the human enzymes, which belong to the same P450 gene
      families. Mean catalytic activities (on basis of mg microsomal protein) of P450
      dependent drug oxidations with eleven substrates were higher in liver microsomes
      of monkeys than of humans, except that humans showed much higher activities for
      aniline p-hydroxylation than those catalyzed by monkeys. However, when the
      catalytic activities of liver microsomes of monkeys and humans were compared on
      the basis of nmol of P450, both species gave relatively similar rates towards the
      oxidation of phenacetin, coumarin, pentoxyresorufin, phenytoin, mephenytoin,
      benzphetamine, ethylmorphine, erythromycin, and nifedipine, while the aniline p
      hydroxylation was higher and bufuralol 1'-hydroxylation was lower in humans than
      monkeys. On the other hand, the immunochemical properties of P450 proteins and
      the activities of P450-dependent drug oxidation reactions in dogs, guinea pigs,
      and rats were somewhat different from those of monkeys and humans; the
      differences in these animal species varied with the P450 enzymes examined and the
      substrates used. The results presented in this study provide useful information
      towards species-related differences in susceptibilities of various animal species
      regarding actions and toxicities of drugs and xenobiotic chemicals.

PMID- 9195022
TI  - A prospective outcome study of rehabilitation programs and anterior cruciate
      ligament reconstruction.
AB  - We evaluated the outcome of and compared two rehabilitation programs (clinic
      based versus home) after a mid-third patellar autograft reconstruction of the
      anterior cruciate ligament. Thirty-seven patients (28 male, 9 female; average
      age, 24.1 years) completed the study. Fifteen of these patients received clinic
      based rehabilitation (three visits per week for 6 weeks prescribed), and 22
      patients received home-based physical therapy (number of visits determined by
      patient response). Knee ROM, Lysholm, Visual Analogy Scale, (VAS) pain rating,
      hop test, KT-1000, and Sickness Impact Profile (SIP) were evaluated
      preoperatively and postoperatively. All patients reported good satisfaction with
      the function of their knee at average follow-up of 21.6 months (range, 12 to 48).
      Patients managed by home rehabilitation averaged 2.85 visits as compared with
      14.2 for clinic-centered patient (P < .05). There were no differences in
      functional or subjective outcomes in the different postoperative rehabilitation
      regimens, with both groups reporting high satisfaction and improved quality of
      life. Cost savings in the home rehabilitation group were significant.

PMID- 9195023
TI  - Cruciate ligament graft intra-articular distances.
AB  - Although the length of the anterior and posterior cruciate ligaments have been
      well characterized in the literature, we are not aware of any studies of the
      actual length of grafts used in reconstruction of these ligaments. We dissected
      and measured these distances for 18 cadaver knees of varying size and sex. The
      precise location of ideal guide pin placement was located based on current
      recommendations, and the intra-articular graft length was measured with a
      micrometer by two separate observers. We found that the average intra-articular
      graft length for the anterior cruciate ligament is 23.56 mm (SD, 0.98 mm), the
      posterior cruciate ligament is 30.72 mm (SD, 2.61 mm) and the patella tendon
      graft intertendinous distance is 43.33 mm (SD, 4.21 mm) We conclude that the
      intra-articular distance for cruciate ligament grafts is less than published
      values for the ligaments themselves, and that the patella tendon graft is of
      adequate length to be used for reconstruction of these ligaments.

PMID- 9195024
TI  - Failure strengths of suture versus biodegradable arrow for meniscal repair: an in
      vitro study.
AB  - Advances in our understanding of meniscal function and consequences of
      menisectomy have spawned meniscal repair techniques that yield success rates
      approaching 90% in properly selected patients. Biodegradable implants have been
      fashioned for meniscal fixation to simplify the technique and minimize
      neurovascular complications. We performed the current study to determine the in
      vitro biomechanical behavior of the BIOFIX Meniscal Arrow, a polylactic acid tack
      developed for meniscal repair. Eight pairs of menisci were harvested from
      cadaveric knees kept frozen before testing. Peripheral vertical tears were
      created in the posterior horn of all menisci, and each was subsequently repaired
      using a vertical loop suture of 2-0 Ethibond and a Meniscal arrow. Ultimate load
      to failure of each method was determined on a Hounsfield H25KM Universal Testing
      machine. The mean failure load for the suture group was 58.3 N compared with the
      Arrow group mean of 29.6 N (P < .001). All sutures failed by rupture at the knot
      but did not pull through the meniscus. All but one of the arrows failed by
      pulling out of the meniscus. The Arrows also permitted gapping at the repair site
      at considerably lesser loads than the sutures subject to strain. The concept of a
      biodegradable tack is appealing. Vertical loop sutures should be the standard by
      which their biomechanical performance is judged. We suggest modifications to the
      Arrow design that could enhance the fixation strength of this implant.

PMID- 9195025
TI  - Technique for arthroscopic suture fixation of displaced tibial intercondylar
      eminence fractures.
AB  - Our modification of the technique for arthroscopic reduction and suture fixation
      of displaced fractures of the intercondylar eminence of the tibia is described in
      this report. The advantages of this technique include no retained hardware,
      ability to treat comminuted (type IV) injuries, and technical simplicity. In
      combination with a relatively aggressive postoperative rehabilitation program,
      the treatment of six adults with this technique is described.

PMID- 9195026
TI  - Local anesthesia for arthroscopic surgery of the ankle using pethidine or
      prilocaine.
AB  - Investigation of the intraoperative and postoperative pain-reducing effect of
      pethidine (meperidine) as compared with local anesthetics given into the ankle
      joint was performed, in a comparative and double-blind fashion, in 20 patients
      subjected to arthroscopy of the ankle, diagnostic and surgical procedures. These
      patients were randomly assigned to one of two groups. Group A consisted of 10
      patients receiving prilocaine 5% with adrenaline and the patients of group B
      received pethidine 5% with adrenaline intraarticularly. During arthroscopy, the
      patients reported on pain and discomfort using visual analog scales. Ratings did
      not differ between the two groups, but six patients would not have chosen the
      local anesthetic technique again. Postoperatively, all patients rated their pain
      and discomfort at rest and at movement (1, 2, 3, 5, 6, 8, and 24 hours and at
      three times during 2 following days). No differences were found between the two
      groups, except for pain at rest through the whole observation period when
      significant lower values for pethidine. There were no differences in use of
      analgesics between the two groups. The current study indicates that pethidine is
      a potential alternative to prilocaine in arthroscopy of the ankle.

PMID- 9195027
TI  - Histological and structural study of the adhesive tissue in knee fibroarthrosis:
      a clinical-pathological correlation.
AB  - In fibroarthrosis of the knee, it is still unknown if joint range of motion is
      affected by anatomopathological differences in adhesive tissue, such as tissue
      maturity, location, and quantity. A retrospective study of 78 patients who
      underwent arthoscopic arthrolysis was performed to determine a correlation
      between location of adhesions and preoperative range of motion (ROM). In another
      17 patients, a histological and structural evaluation of adhesive tissue was
      performed. Based on vascularization, number and shape of cells, and collagen
      fiber orientation, the adhesive tissue was classified into three groups: low,
      medium, and high maturity. Preoperative joint ROM and the time of onset of joint
      stiffness was correlated with the degree of adhesion tissue maturity. A strong
      and statistically significant correlation between the location of adhesions and
      joint restriction was found. However, histological and structural evaluation
      showed no correlation between the degree of tissue maturity, the time of onset of
      joint stiffness, and the amount of joint ROM.

PMID- 9195028
TI  - Antegrade drilling for osteochondritis dissecans of the knee.
AB  - Twenty-four knees with osteochondritis dissecans of the femoral condyles failed a
      conservative program and were treated with antegrade drilling. To our knowledge,
      this represents the largest reported series using this technique. The average age
      at the time of surgery was 13 years 6 months. Seventeen patients had open physes,
      and four were skeletally mature. Nineteen lesions involved the medial femoral
      condyle, and five involved the lateral femoral condyle. The average follow-up was
      5 years. Postoperative evaluation included rating by the International Knee
      Documentation Committee (IKDC) form and the Hughston Rating Scale for
      osteochondritis dissecans. Twenty of the 24 lesions healed after antegrade
      drilling, and the average time of healing was 4 months. According to the criteria
      on the IKDC grading form, 14 were normal, 6 nearly normal, three abnormal, and
      one severely abnormal. The results of the Hughston Rating Scale were similar: 15
      were excellent, seven good, one fair, and one poor. Only two of the four
      skeletally mature patients healed after antegrade drilling. Antegrade drilling is
      an effective method of treatment for osteochondritis dissecans of the knee that
      occurs in adolescents with open physes. This operation is not as likely to result
      in a successful outcome in patients with closed physes; consequently, other
      methods should be considered in skeletally mature patients.

PMID- 9195029
TI  - The anatomic origin of the posterior cruciate ligament: where is it? Reference
      landmarks for PCL reconstruction.
AB  - There is a lack of defined reference points for reproducible femoral tunnel
      placement during posterior cruciate ligament (PCL) reconstruction. The PCL,
      consisting of two major bands, anterolateral (AL) and posteromedial (PM), has a
      femoral origin that spans 3 cm, which cannot be covered by a substitute graft
      positioned in one femoral tunnel to reconstruct the PCL. The purpose of this
      study was to define the location of the anatomic origin of both bands of the PCL
      in reference to local anatomy to develop landmarks that can be used to
      reproducibly position two femoral tunnels (one to each band's origin) during PCL
      reconstruction. The anatomy of the PCL origin was dissected and studied in 20
      knees at the time of total knee replacement. The central origin point for each
      band was marked, and its distance was measured in reference to three axes. The AL
      band centrally originated 13 +/- 0.5 mm posterior to the medial articular
      cartilage-intercondylar wall interface and 13 +/- 0.5 mm inferior to the
      articular cartilage-intercondylar roof interface. The PM band centrally
      originated 8 +/- 0.5 mm posterior to the medial articular cartilage-intercondylar
      wall interface and 20 +/- 0.5 mm inferior to the articular cartilage
      intercondylar roof interface. These distances were noted to be relatively
      constant despite varying knee morphologies and size. For this reason, referencing
      the articular cartilage-intercondylar roof, and wall interfaces may be used as a
      method to facilitate more reproducible anatomic femoral tunnel placements during
      PCL reconstruction.

PMID- 9195030
TI  - Arthroscopic anterior cruciate ligament reconstruction using a patellar tendon
      graft in press-fit technique: surgical technique and follow-up.
AB  - A modified endoscopic technique for anterior cruciate ligament (ACL)
      reconstruction using an autologous patellar tendon graft is described using the
      early results for 120 patients. A special technique using an oscillating hollow
      saw allows for the rapid and standardized harvest of cylindrical bone plugs,
      ensuring safe and adequate femoral press-fit fixation. The complications
      encountered included one fracture of a bone back on plugging in as well as two
      cases with revision procedures for interference screw fixation due to
      insufficient femoral anchorage. Within the framework of a prospective study, all
      120 patients underwent a control arthroscopy after the first postoperative year
      showing viable and mechanically stable grafts in 64 (53.3%) of the patients. In
      44 patients (36.7%), viable though somewhat lax grafts were found, whereas the
      remaining 12 patients (10%) only showed insufficient tissue residues. All of
      these cases were the result of a ventral misplacement of the femoral insertion
      site representing the primary complication of transtibial technique. The results
      of the control arthroscopies showed a highly significant correlation with the
      clinical results for the IKDC score obtained in a follow-up after an average 29
      (18 to 36) months. The results for stability according to the IKDC rating scale
      showed a normal or near-normal knee function in 76.7%. With regard to the
      subjective results in the IKDC rating scale, 83.3% of the patients (n = 100)
      assessed their knee function as normal or almost normal. The location and
      positioning of the femoral and tibial tunnel were evaluated in an exact
      radiographic evaluation showing an "ideal position" of the graft in only 94 cases
      (78.3%). Statistically, a significant correlation of stability with the femoral
      fixation site could be shown.

PMID- 9195031
TI  - The relationship of suture anchor failure and bone density to proximal humerus
      location: a cadaveric study.
AB  - The purpose of this study was to evaluate spatial variations in the pullout
      strength of a suture anchor in the proximal humerus, and to correlate any
      differences with the local mineral density (BMD). Screw-type suture anchors
      threaded with wire sutures were inserted at six different anchor insertion sites
      in 11 human cadaveric humeri (average age, 80 years). Load to failure tests with
      forces applied in line with the axis of insertion were performed, and bone
      mineral density measurements were then made at these sites. The greater
      tuberosity showed anterior and posterior differences in anchor pullout force (P =
      .03), with the posterior portion showing higher strength (154 N) than the
      anterior area (96 N). Neither the lesser tuberosity (185 N anterior area and 177
      N posterior area) nor the humeral neck (170 N anterior and 174 N posterior area)
      showed significant differences, and they were statistically equivalent to the
      greater tuberosity. There was no demonstrable difference in BMD at any of the six
      sites tested. There is no support for the hypothesis that significant differences
      in load to failure exist among the lesser tuberosity, humeral neck, and greater
      tuberosity. Also, there is no support for the hypothesis that the load to failure
      variations for the proximal humerus are dependent on BMD. Bone mineral density
      appears to have no correlation with the pullout strength of a screw-type suture
      anchor.

PMID- 9195032
TI  - Traction versus distension for distraction of the joint during hip arthroscopy.
AB  - Distraction is the most popular technique used in hip arthroscopy. It has been
      postulated that, if adequate distraction cannot initially be achieved with
      traction, it will be overcome by distension. The purpose of this study is to
      quantitate the additive effects of traction and distension in achieving
      distraction of the hip joint for arthroscopy. Eleven consecutive patients
      undergoing hip arthroscopy in the supine position on a fracture table were
      studied. Radiographs of the hip were obtained before and immediately after
      applying 50 pounds of traction. The hip was then immediately distended with 40 mL
      saline, and a third radiograph was obtained. After correcting for magnification,
      distraction was measured for traction alone (DT) and traction plus distension
      (DTD). A paired t-test was used to compare DT and DTD. Additionally, the ratio of
      distraction attributed to distension was compared with distraction attributed to
      traction ([DTD--DT]/DT) and was defined as the delta percent (delta %). Adequate
      distraction for arthroscopy was able to be achieved in all cases. Distraction due
      to traction alone (DT) ranged from 2.8 mm to 10.3 mm, with an average of 6.2 mm.
      Distraction due to traction plus distension (DTD) ranged from 4.8 m to 10.3 mm,
      with an average of 7.2 mm. The difference between DT and DTD was statistically
      significant (P < .05). The change in distraction due to distension (delta %)
      ranged from 0% to 81% with an average of 22%. This study shows that distension
      may facilitate distraction but the degree is variable.

PMID- 9195033
TI  - Arthroscopically assisted treatment of acute septic knees in infants using the
      Micro-Joint Arthroscope.
AB  - Five infants with an acute hematogenous septic arthritis of the knee were treated
      with arthroscopically assisted drainage using the Micro-Joint Arthroscope (MJA;
      Linvatec, Largo, FL) combined with antibiotic therapy and early postoperative
      motion. The average patient age was 16 months (range, 4 to 24 months). No
      surgical or anesthetic complications occurred. All knees were clinically and
      radiologically normal at an average follow-up of 26 months.

PMID- 9195034
TI  - Internal fixation strength of suture anchors--update 1997.
AB  - Two new areas of anchor development are biodegradable anchors and "mini" anchors.
      The group of biodegradable anchors tested include the Bio-Anchor, LactoSorb,
      Biofix, Bio-Statak, Mini Screw suture anchor, DePuy 4.5 molded, DePuy 4.5
      machined, DePuy 3.5 machined, TAG Wedge 4, TAG Rod 2, TAG Wedge 3, TAG Wedge 2,
      and Stealth. "Mini anchors" have drill holes or minor diameters of < 2.2 mm.
      Those tested include the Mini Revo and Bio-Anchor, miniHarpoon, mini Mitek and
      Fast in 3, Statak 1.5 and 2.5, SB 2 and PeBA 3, Corkscrew 5, Corkscrew 3.5, and
      Fastak A2, Ogden 2.5, TAG Wedge 2, ROC 1.9, and Questus 2.5. Additional anchors
      tested that fit neither category include the Anspach, Questus 3.5 and 5.0, SB 3
      and PeBA-C, Ogden 3.5, Fast in 4, Ultrafix, and the ROC 3.5, ROC 2.8, ROC 2.3,
      and ROC XS. An anchor comparison, using an established protocol in fresh porcine
      femurs, recorded failure strength, failure mode, eyelet size, minor and major
      diameters, and drill hole sizes. Except for the Bio-Anchor and TAG Wedge 2,
      biodegradable anchors tend to be larger to compensate for their lower strength
      relative to metal. Biodegradable screw anchors' predominant failure mode was
      eyelet cutout, whereas biodegradable nonscrew anchors failed to predominantly by
      anchor pullout. From an initial mechanical perspective, these biodegradable
      anchors perform acceptably. Both biodegradable and "mini" anchors include screw
      and nonscrew designs. As expected, screw designs perform well and generally fail
      at higher loads than nonscrew anchors. Although biodegradable anchors, as a
      group, are not as strong as metal anchors, they are stronger than the sutures for
      which they are designed. The move to smaller ("mini") and biodegradable anchors
      is supported by these data. Whether an anchor fails at twice the suture breaking
      strength or 10 times the suture breaking strength should make no difference.

PMID- 9195035
TI  - Oblique menisco-meniscal ligament of the knee.
AB  - Anomalies of the intra-articular anatomy of the knee can be confusing to the
      unwary arthroscopist. The case that follows shows a variant of the anterior
      intermeniscal ligament, which was not previously appreciated by the authors yet
      had been previously described. Awareness of this variant will be especially
      pertinent in anterior cruciate ligament reconstruction, where its identification
      is more likely.

PMID- 9195036
TI  - Noninvasive distraction for ankle arthroscopy.
AB  - This article reviews a simple technique used for noninvasive traction in an ankle
      arthroscopy. The author describes a modification of a previously described
      noninvasive ankle distraction technique using an inexpensive gauze roll.

PMID- 9195037
TI  - Radial avulsion of the triangular fibrocartilage complex in acute wrist trauma: a
      new technique for arthroscopic repair.
AB  - The advantages of arthroscopically assisted treatment of intraarticular distal
      radius fractures, especially the detection of additional carpal lesions, also
      focus attention on special surgical techniques for operating on these injuries
      within the same session. When we consider the biomechanical situation, various
      kinds of triangular fibrocartilage complex (TFCC) lesions, and their arthroscopic
      aspects, there are probably two possibilities for surgical treatment that are
      similar to arthroscopic meniscal surgery: resection of flap tears and the
      refixation of peripherally disinserted TFCC. Avulsions from the ulnar styloid or
      from the ulnar collateral ligament and the extensor carpi ulnaris tendon can
      easily and satisfactorily be treated by convenient arthroscopic suture
      techniques, whereas the reattachment of the triangular disc in the sigmoid notch
      is very tricky. This problem is solved by a recently developed procedure using
      the so-called T-Fix-device (Acufex), which provides the possibility of
      transosseus refixation by closed arthroscopic procedure and therefore guarantees
      the principle of minimal invasive surgery.

PMID- 9195038
TI  - Arthroscopic one-piece excision technique for the treatment of symptomatic
      lateral discoid meniscus.

PMID- 9195039
TI  - Alkylsyringamides, new inducers of Agrobacterium tumefaciens virulence genes.
AB  - The virulence genes of Agrobacterium tumefaciens are specifically activated by
      plant phenolic compounds and allow this organism to genetically transform plant
      cells. New types of phenolic compounds, three phenol amides derived from syringic
      acid, were synthesized. Introduction of an amide group in syringic acid strongly
      enhances its vir gene inducing activity.

PMID- 9195040
TI  - Molecular characterization of the prokaryotic efp gene product involved in a
      peptidyltransferase reaction.
AB  - The translation factor EF-P is required for efficient prokaryotic peptide bond
      synthesis on 70S ribosomes from fMet-tRNAfMet. This protein has been purified
      from Escherichia coli cells and the gene, efp, encoding it has been cloned and
      sequenced. We have isolated recombinant clones which overexpress a protein that
      co-migrates with purified EF-P upon SDS-PAGE analysis. Using these clones, we
      report the purification, crystallization and initial characterization of the efp
      gene product. The mechanism by which EF-P stimulates peptide-bond synthesis was
      studied using several antibiotics that inhibit translocation, peptide-bond
      synthesis and decoding. The stimulation of peptidyltransferase by EF-P was not
      inhibited by antibiotics that affect translocation and occupation of the A site
      (in the elongation state), ie thiostrepton, viomycin, neomycin and fusidic acid
      but was inhibited by streptomycin as well as by inhibitors of
      peptidyltransferase, chloramphenicol and lincomycin. This observation and the
      requirement for L16 but not for the L7/L12 nor L6 or L11 r-proteins suggest that
      the binding site for EF-P may overlap the peptidyltransferase center of the
      ribosome.

PMID- 9195041
TI  - Site directed DNA joining.
AB  - We have previously identified a cDNA encoding part of the amino terminal portion
      of the large subunit of replication factor c (RF-C, AP-1), which we have named
      VDJP. Analysis of VDJP demonstrated that it has amino acid homology to bacterial
      DNA ligases and specific binding to the nonamer portion of the V(D)J
      recombination signal sequence motif. In this report, we demonstrate that VDJP is
      capable of forming a covalent bond between DNA fragments in a sequence dependent
      fashion. The VDJP mediated DNA ligation reaction is neither dependent on the
      presence of compatible DNA ends nor on sequence homology between the DNA
      fragments that are joined. Furthermore, we show that the covalent junction
      between the DNA fragments is resistant to proteases and phenol, and therefore not
      protein linked.

PMID- 9195042
TI  - Effect of self association of bis-ANS and bis-azo dyes on protein binding.
AB  - A correlation was found between the ability of dyes (ANS, bis-ANS, Congo red,
      Evans blue) to form self-associated supramolecular structures in water and their
      tendency to form complexes with proteins. The self-association ability of dyes
      was measured as the resistance of a molecular sieve to their penetration.
      Quantitative evaluation of dye-protein interaction involved measuring the effect
      of dye on antibodies that agglutinate sheep red blood cells. Enhancement of
      agglutination by dye was assumed to represent its protein complexation ability.
      The results confirm that, relative to monomers, self-associated ligands also have
      altered protein binding properties.

PMID- 9195043
TI  - Expression of the release factor eRF1 (Sup45p) gene of higher eukaryotes in yeast
      and mammalian tissues.
AB  - Polypeptide chain termination in eukaryotic cells is mediated in part by the
      release factor eRF1 (Sup45p). We have isolated and characterised cDNAs encoding
      this translation factor from Syrian hamster (Mesocricetus auratus) and human
      (Homo sapiens) Daudi cells. Comparison of the deduced amino acid sequence of
      these new eRF1 (Sup45p) sequences with those published for Saccharomyces
      cerevisiae, Arabidopsis thaliana, Xenopus laevis and human indicates a high
      degree of amino acid identity across a broad evolutionary range of species. Both
      the 5' and 3' UTRs of the mammalian eRF1 (Sup45p)-encoding cDNAs show an
      unusually high degree of conservation for non-coding regions. In addition, the
      presence of two different lengths of 3' UTR sequences in the mammalian eRF1
      (Sup45p) cDNAs indicated that alternative polyadenylation sites might be used in
      vivo. Northern blot analysis demonstrated that eRF1 (Sup45p) transcripts of
      differing length, consistent with the use of alternative polyadenylation sites,
      were detectable in a wide range of mammalian tissues. The Xenopus, human and
      Syrian hamster eRF1 (Sup45p) cDNAs were shown to support the viability of a
      strain of S cerevisiae carrying an otherwise lethal sup45::HIS3 gene disruption
      indicating evolutionary conservation of function. However, the yeast strains
      expressing the heterogenous eRF1 (Sup45p) showed a defect in translation
      termination as defined by an enhancement of nonsense suppressor tRNA activity in
      vivo. Western blot analysis confirmed that Xenopus eRF1 (Sup45p) was primarily
      ribosome-associated when expressed in yeast indicating that the ribosome-binding
      domain of eRF1 (Sup45p) is also conserved.

PMID- 9195044
TI  - Alkylation at the active site of the D-3-hydroxybutyrate dehydrogenase (BDH), a
      membrane phospholipid-dependent enzyme, by 3-chloroacetyl pyridine adenine
      dinucleotide (3-CAPAD).
AB  - The structure of the rat liver's D-3-hydroxybutyrate dehydrogenase (BDH) active
      site has been investigated using an affinity alkylating reagent, the 3
      chloroacetyl pyridine adenine dinucleotide (3-CAPAD). This NAD+ analogue reagent
      strongly inactivates the enzyme following a concentration- and time-dependent
      process with a stoichiometry of approximately 1. The reagent reacts at the
      coenzyme binding site as revealed by the efficient protection by NADH. The effect
      of 3-CAPAD is stronger with the enzyme into its natural membrane environment than
      with the lipid-free purified apoBDH or with the reconstituted apoBDH
      mitochondrial phospholipid complex. The pH-dependent effect on the inactivation
      process is in agreement with the participation of protons in the catalytic
      mechanism of BDH. Furthermore, this study exhibits the phospholipid activating
      role in BDH catalytic activation.

PMID- 9195045
TI  - Purification of an atypical bovine interferon induced in response to heat shock
      in bovine cultured cells. Characterization in comparison with the classical
      alpha, beta and gamma interferon.
AB  - Heat-shock induced factor (HSIF) was excreted by bovine MDBK cells during their
      recovery period after a heat shock. This factor has the capacity to induce 2',5'
      oligoadenylate synthetase activity, an enzyme generally by interferon treatment
      (J Biol Chem (1987) 262, 4806-4811). We have observed that an antiviral state was
      also produced in response to heat shock. HSIF was purified 10,000-fold and
      different techniques showed a copurification of both activities. Certain
      properties of HSIF were established, such as its molecular mass (45 kDa) and
      isoelectric point (6.8). This cytokine was acid-sensitive as IFN gamma (type II)
      and temperature labile contrarily to alpha, beta and gamma bovine IFN.
      Immunoprecipitation and comparative chromatography on lectines or polynucleotides
      established that HSIF was structurally different from the three classes of bovine
      IFN. Moreover, two-dimensional electrophoresis and comparative analysis of [35S]
      methionine-labeled proteins induced by HSIF alpha, beta or gamma bovine IFN
      showed that HSIF induces a specific set of proteins. Taken together, all these
      results strongly suggest that HSIF is a new atypical bovine interferon induced in
      response to heat shock.

PMID- 9195046
TI  - In vitro properties and organ uptake of rat band 3 cross-linked erythrocytes.
AB  - Chemical conditions for cross-linking rat erythrocytes with
      bis(sulfosuccinimidyl)suberate (BS3) and 3,3' dithiobis(sulfosuccinimidyl
      propionate) (DTSSP) have been studied. These two cross-linking reagents seem to
      react with band 3 proteins in rat erythrocyte membrane. Two different conditions
      have been assayed using different cell/cross-linker concentration ratios. Similar
      cell volumes were observed in cross-linked rat erythrocytes compared to rat
      control erythrocytes. Cell yields after cross-linking account for about 65% when
      a high ratio of cell-to-cross-linker was used. Slightly lower cell yields (about
      62%) were obtained when this ratio was reduced. Estimation of band 3 cross
      linking by gel electrophoresis revealed a level of cross-linking of around 45%
      and 50% at the different conditions used. In vivo behavior of these modified rat
      erythrocytes revealed that they do not circulate, showing a predominant
      localization in the liver. This effect is evident from the concentration (5 mM
      BS3 or DTSSP) used. Based on these results, BS3 and DTSSP can be considered as
      useful tools to cross-link rat erythrocyte band 3 and to target rat erythrocytes
      to the liver.

PMID- 9195047
TI  - New aspects of fibrinolytic proteins in brain development.

PMID- 9195048
TI  - Involvement of reactive oxygen species in the induction of chemokine JE/MCP-1
      gene by phorbol-12-myristate-13-acetate in Balb 3T3 cells.
AB  - The induction of JE/MCP-1 gene by TPA was transcriptionally suppressed by
      antioxidants such as pyrrolidine dithiocarbamate (PDTC) or trimethylthiourea
      (TMTU) in Balb 3T3 cells, whereas that of other early response genes, c-fos or
      egr-1, was not affected by these agents. Induction of the JE gene by TNF alpha or
      serum was not completely inhibited by these antioxidants inhibited an increase in
      intracellular oxidized state of cells treated with TPA. Next we examined the
      transcriptional regulatory region of the rat JE gene to determine the genomic
      target of active oxygen species. The chloramphenicol acetyltransferase (CAT)
      reporter gene, containing the 5'-upstream region approximately 2.6 kb DNA from
      the cap site, was transfected into Balb 3T3 cells. The CAT activity induced by
      TPA increased in parallel with the endogenous JE and mRNA level, and the increase
      was inhibited by the antioxidants. The essential region for this response in the
      upstream region was within the -2.6 to -2.0 kb region, and further defined to 
      2,224 to -2,069 bp which contained and NF kappa B-binding element. Gel shift
      analysis indicated that the nuclear factors that bound to this essential element
      contained NF kappa B, and that NF kappa B activity was stimulated by TPA and
      inhibited by PDTC. These results suggest that active oxygen species are involved
      in induction of the JE gene caused by TPA in Balb 3T3 cells, through NF kappa B
      activation.

PMID- 9195049
TI  - Association of hnRNP S1 proteins C2 and D2 with vimentin intermediate filaments.
AB  - S1 proteins A-D are hnRNP proteins which were originally isolated from nuclei of
      various tissues, by selective extraction of pH 4.9 from the supernatants of
      nuclei mildly treated with DNase I or RNase A. In the present study, a hybridoma
      was isolated which produced a monoclonal antibody that reacted specifically with
      S1 proteins C2 and D2. When the antibody was used in indirect immunofluorescence
      staining of cultured cells, it stained, in addition to the nuclei, the
      cytoskeleton-like fibrous structures in the cytoplasm. We demonstrate that the
      cytoskeletal filaments are vimentin intermediate filaments. This is the first
      report on the hnRNP protein-association with cytoskeleton, and will help to
      clarify cytoplasmic mRNA localization as well as cytoplasmic distribution of
      hnRNP proteins.

PMID- 9195050
TI  - Le(X) structure enhances myocardial differentiation from embryonic stem cells.
AB  - alpha-1,3-Fucosyltransferase (Fuc T IV) cDNA was placed under the control of beta
      actin, cytomegalovirus enhancer/promoter and transfected into embryonic stem
      cells. The transfected cell clones with integrated cDNA (positive clones)
      differentiated more efficiently into myocardial cell clones without integrated
      cDNA (negative clones) or parental cells. Furthermore, myocardial cells
      differentiated from the positive clones survived longer than those differentiated
      from the negative clones or parental cells. These results indicate that Lewis X
      structure, the product of Fuc T IV, enhances myocardial differentiation. The
      mechanism of the phenomenon is discussed on relation to integrin action.

PMID- 9195051
TI  - ATP-dependent lysis of isolated lysosomes by basic substances and acidic
      ionophores.
AB  - We established an in vitro cell-free system with which to evaluate the effects of
      basic substances and acidic ionophores on the internal pH and integrity of FITC
      dextran (FD)-loaded lysosomes isolated from the rat liver. In this system, basic
      substances and acidic ionophores not only increased the internal pH dose
      dependently, but also disrupted the lysosomes in the presence of Mg-ATP, which
      was detected as the release of FD from lysosomes. All of the vacuoligenic bases
      and acidic ionophores, but none of the non-vacuoligenic bases or neutral
      ionophores disrupted the lysosomes, suggesting that this phenomenon is an vitro
      manifestation of vacuole formation induced in vivo by basic substances and acidic
      ionophores. Lysosome disruption required a functional proton pump as well as
      permeant anions. It was inhibited by inhibitors of the lysosomal proton pump,
      including bafilomycin A1, N-ethylmaleimide (NEM), and N, N'
      dicyclohexylcarbodiimide (DCCD), or when permeant anions were replaced with
      impermeant anions. It was also suppressed by increasing the osmotic pressure of
      the surrounding medium, suggesting that it was caused by osmotic swelling of
      lysosomes induced by protonated bases or cations characteristic of particular
      ionophores that accumulated within lysosomes driven by the proton pump.
      Furthermore, this lysosomal disruption was inhibited by cytosolic factors. This
      phenomenon will provide an in vitro system for studies on osmoregulation and the
      intracellular dynamics of the lysosomal system, including membrane fusion.

PMID- 9195052
TI  - Formation of actin filament networks in cultured rat hepatocytes treated with
      DMSO and glucagon.
AB  - Actin filament organization may play an important role in the maintenance of
      differentiated functions in epithelial cells. We previously reported our success
      in inducing and maintaining gap junctions, which are two kinds of differentiated
      function, in primary rat hepatocytes cultured with 2% DMSO and 10-7 M glucagon.
      In the present study, we demonstrated the formation of actin filament networks in
      the hepatocytes cultured with 2% DMSO and 10-7 M glucagon. Actin filaments in
      hepatocytes cultured in medium with only 2% DMSO added from 96 h after plating
      were concentrated under the plasma membrane and were observed to be
      circumferential. In hepatocytes cultured in the medium with both 2% DMSO and 10-7
      M glucagon added from 96 h, not only the circumferential actin filaments but also
      the formation of actin filament networks were observed and the networks developed
      well with time in culture. The networks were observed as a dome-like structure
      under the cell face and terminated at the circumferential actin filaments. They
      were composed of electron-dense star-like vertices connected by microfilament
      bundles of varying length and were also very sensitive to the actin disruptor
      cytochalasin B. However, during the network formation, there were no significant
      increases in the amounts of actin protein and mRNA. The actin filament networks
      of the hepatocytes in this culture system might be closely related to the
      maintenance of differentiated functions.

PMID- 9195053
TI  - Secretion of slime, the extracellular matrix of the plasmodium, as visualized
      with a fluorescent probe and its correlation with locomotion on the substratum.
AB  - Slime, the extracellular matrix of Physarum plasmodium, is secreted by the
      exocytosis of a vesicles that contain a slime precursor. Using an antibody raised
      against biochemically purified slime, we detected the intracellular localization
      of the slime vesicle. Slime vesicles are abundant in the advancing front of the
      plasmodium, as confirmed by electron microscopic observation in two different
      cross-sectional angles. Screening various reagents, we found that rhodamine
      phosphatidylethanolamine (Rh-PE) binds specifically to slime in both its
      intravesicular and extracellular forms, as confirmed by immunoelectron microscopy
      using an antibody against fluorochrome rhodamine. The plasmodia vitally stained
      with Rh-PE exhibited dynamic fluorescent patterns during the course of
      locomotion. The fluorescence was conspicuous at the periphery of the leading
      pseudopods and oscillated according to the shuttle streaming that accompanied the
      relaxation and contraction of the periphery; it was intense in the relaxation
      phase when pseudopods extended, and became weak in the contraction phase when
      pseudopods contracted. The results collectively mean that the slime vesicles
      carried by the cytoplasmic streaming accumulated prior to secretion at the
      advancing margin of the plasmodium.

PMID- 9195054
TI  - Characterization of the carrot beta-tubulin gene coding a divergent isotype, beta
      2.
AB  - Four different beta-tubulin clones were isolated from carrot genomic and cDNA
      libraries. Their nucleotide sequences were determined 1 and their predicted amino
      acids were compared with each other. The predicted amino acid composition of the
      C-terminal region of three of them (beta-1, 3, 4) resembled one another, but that
      of one isotype (beta-2) was divergent. The beta-2 tubulin included two hydroxyl
      amino acids, serine and threonine, and consisted of a lower number of negatively
      charged amino acids than the others in the C-terminal region. The predicted
      hydrophobicity profile of the beta-2 tubulin around the residue 200 is less
      hydrophobic than beta-1, but it is still more hydrophobic than those of animal
      and fungal beta-tubulins. The beta-2 gene was transcribed in cultured cells and
      flowers, while the beta-1 gene was ubiquitously transcribed in cultured cells,
      roots, shoots and flowers. When the predicted amino acids of plant tubulin were
      compared with those of other organisms, substitutions from non-polar amino acids
      to those with hydroxyl group were conspicuous in the region corresponding to the
      third exon in the plant genes.

PMID- 9195055
TI  - Peritonitis: update on pathophysiology, clinical manifestations, and management.

PMID- 9195056
TI  - Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case
      history and review.
AB  - The spectrum of disease caused by parvovirus B19 has been expanding in recent
      years because of improved and more sensitive methods of detection. There is
      evidence to suggest that chronic infection occurs in patients who are not
      detectably immunosuppressed. We report the case of a young woman with recurrent
      fever and a syndrome indistinguishable from chronic fatigue syndrome. After
      extensive investigation, we found persistent parvovirus B19 viremia, which was
      detectable by polymerase chain reaction (PCR) despite the presence of IgM and IgG
      antibodies to parvovirus B19. Testing of samples from this patient suggested that
      in some low viremic states parvovirus B19 DNA is detectable by nested PCR in
      plasma but not in serum. The patient's fever resolved with the administration of
      intravenous immunoglobulin.

PMID- 9195057
TI  - Multivariate analysis of risk factors for infection due to penicillin-resistant
      and multidrug-resistant Streptococcus pneumoniae: a multicenter study.
AB  - Pneumococcal disease was studied prospectively to determine the risk factors
      associated with resistance to penicillin and other antibiotics. One hundred
      twelve clinically significant pneumococcal isolates were recovered from 95
      patients. Approximately one-half (49.47%) of the cases were due to penicillin
      resistant strains. Multivariate analysis showed that previous use of beta-lactam
      antibiotics (odds ratio [OR], 2.81; 95% confidence interval [CI], 0.95-8.27),
      alcoholism (OR, 5.22; 95% CI, 1.43-19.01), and noninvasive disease (OR, 4.53; 95%
      CI, 1.54-13.34) were associated with penicillin resistance, whereas intravenous
      drug use (OR, 0.14; 95% CI, 0.03-0.74) was not. Statistical analyses of the
      variables associated with resistance to multiple antibiotics detected age of
      younger than 5 years (OR, 16.79; 95% CI, 1.60-176.34) or of 65 years or older
      (OR, 4.33; 95% CI, 1.42-13.21) and previous use of beta-lactam antibiotics by
      patients with noninvasive disease (OR, 7.92; 95% CI, 1.84-34.06) as parameters
      associated with increased risk. We conclude that multivariate analysis provides
      clues for empirical therapy for pneumococcal infection.

PMID- 9195058
TI  - Impact of tuberculosis control measures and crowding on the incidence of
      tuberculous infection in Maryland prisons.
AB  - Our aim was to determine the incidence of tuberculin skin test (TST) conversion
      in the Maryland state correctional system. We conducted a historical longitudinal
      cohort study. A sample of 1,289 inmates, incarcerated in 16 of 23 prisons, who
      had a negative TST and a second test within 24 months was selected. The incidence
      of recent conversion was 6.3 per 100 person-years. Risk factors for conversion
      included high prison-population density (relative risk [RR] = 2.4; 95% confidence
      interval [CI], 1.5-3.8) and incarceration in a higher-security institution (RR =
      2.4; 95% CI, 1.4-4.3). Incarceration in an institution with higher levels of
      isoniazid prophylaxis (> 65% of TST positives) reduced the risk of infection by
      50% (RR = 0.5; 95% CI, 0.3-0.7). Crowding was strongly correlated with risk of
      conversion (r = 0.83; P < .001), while rates of isoniazid prophylaxis initiation
      were inversely correlated with risk of infection (r = -0.82; P < .001). In
      stepwise regression, higher prison-population density was the strongest predictor
      of increased infection. In a final model, inclusion of the rate of isoniazid
      prophylaxis initiation reduced the risk associated with crowding (RR = 1.4; P =
      .4). Annual screening programs for prisons can identify recent conversions that
      may not otherwise be detected.

PMID- 9195059
TI  - Microbiological factors influencing the outcome of nosocomial bloodstream
      infections: a 6-year validated, population-based model.
AB  - All patients (n = 1,745) with nosocomial bloodstream infection identified between
      1986 and 1991 at a single 900-bed tertiary care hospital were studied to identify
      microbiological factors independently associated with mortality due to the
      infection. Patients were identified by prospective, case-based surveillance and
      positive blood cultures. Mortality rates were examined for secular trends.
      Prognostic factors were determined with use of univariate and multivariate
      analyses, and both derivation and validation sets were used. A total of 1,745
      patients developed nosocomial bloodstream infection. The 28-day crude mortality
      was 22%, and crude in-hospital mortality was 35%. Factors independently (all P <
      .05) associated with increased 28-day mortality rates were older age, longer
      length of hospital stay before bloodstream infection, and a diagnosis of cancer
      or disease of the digestive system. After adjustment for major confounders,
      Candida species were the only organisms independently influencing the outcome of
      nosocomial bloodstream infection (odds ratio [OR] for mortality = 1.84; 95%
      confidence interval [CI], 1.22-2.76; P = .0035). The two additional
      microbiological factors independently associated with increased mortality were
      pneumonia as a source of secondary infection (OR = 2.74; 95% CI, 1.87-4.00; P <
      .0001) and polymicrobial infection (OR = 1.68; 95% CI, 1.22-2.32; P = .0014). Our
      data suggest that microbiological factors independently affect the outcome of
      nosocomial bloodstream infection.

PMID- 9195060
TI  - Photo quiz. Choroidal lesions of disseminated cryptococcosis.

PMID- 9195061
TI  - Case-control study of risk factors for Penicillium marneffei infection in human
      immunodeficiency virus-infected patients in northern Thailand.
AB  - A case-control study was done in Chiang Mai, Thailand, comparing risk-related
      behavior and exposures in 80 incident cases of disseminated Penicillium marneffei
      infection in patients with AIDS and 160 control patients with AIDS who did not
      have P. marneffei infection. All subjects were admitted to Chiang Mai University
      Hospital between December 1993 and October 1995. Cases were younger than controls
      (16-30 years vs. > 30 years of age; odds ratio [OR] = 2.22; 95% CI, 1.22-4.07).
      Patients with a recent history of occupational or other exposure to soil,
      especially during the rainy season (May to October), were more likely to present
      with P. marneffei infection (OR = 1.91; 95% CI, 1.04-3.52). History of exposure
      to or consumption of bamboo rats, the only known nonhuman hosts of P. marneffei,
      was not a risk factor for infection. Our data suggest that recent exposure to a
      potential environmental reservoir of organisms in the soil may be associated with
      disseminated P. marneffei infections among patients with AIDS in Northern
      Thailand.

PMID- 9195062
TI  - Haemophilus endocarditis: report of 42 cases in adults and review. Haemophilus
      Endocarditis Study Group.
AB  - To define the clinical, microbiological, and therapeutic characteristics of
      haemophilus endocarditis, we reviewed the charts of 42 adults with haemophilus
      endocarditis (native valve disease, 37; prosthetic valve disease, five) who were
      followed up between 1983 and 1995 in France. The mean duration of symptoms before
      diagnosis was 34 days. The causative Haemophilus species were as follows: H.
      parainfluenzae (26 adults), H. aphrophilus (9), H. paraphrophilus (4), and H.
      influenzae (3). According to the Duke criteria, 38 cases of endocarditis were
      definitive and four were possible. Thirty-nine patients received combination
      antibacterial therapy and three received therapy with a beta-lactam agent alone
      (mean duration, 46 days). Arterial embolism occurred in 15 patients. Cardiac
      surgery was indicated for 18 patients; 16 of these surgeries were performed
      within 3 months. Two patients died of heart failure. In conclusion, haemophilus
      endocarditis is rare and is mainly due to H. parainfluenzae. Although surgery is
      often necessary, haemophilus endocarditis has a favorable prognosis.

PMID- 9195063
TI  - Influenza among hospitalized adults with leukemia.
AB  - Influenza is one of the most important respiratory diseases of mankind, yet scant
      data exist concerning the frequency and clinical course of influenza in severely
      immunocompromised adults. From October 1993 to September 1994, we cultured the
      respiratory secretions of all adults with leukemia who were hospitalized with an
      acute respiratory illness at The University of Texas M.D. Anderson Cancer Center
      in Houston. During a 9-week period from 29 November 1993 to 29 January 1994,
      influenza virus type A (H3N2) was isolated from 15 (33%) of these 45 hospitalized
      adults. Twelve (80%) of the cases of influenza were associated with pneumonia,
      and four patients (33%) with pneumonia died. Patients who died tended to have
      received chemotherapy more recently and to be more myelosuppressed. Autopsy
      examination in two cases revealed histopathologic changes consistent with viral
      pneumonia. During community outbreaks, influenza is a frequent cause of serious
      respiratory disease in hospitalized adults with leukemia. Effective prophylactic
      and therapeutic regimens need to be defined for immunocompromised patients.

PMID- 9195065
TI  - Prevalence of Campylobacter-associated diarrhea among patients infected with
      human immunodeficiency virus.
AB  - We performed a cross-sectional study at an outpatient AIDS clinic to assess the
      prevalence of Campylobacter species in stool specimens from 201 consecutive
      patients infected with human immunodeficiency virus (HIV). We characterized
      campylobacters phenotypically and genetically by using primers for the group of
      common species (i.e., C. jejuni, C. coli, C. lari, and C. upsaliensis) and for
      most individual uncommon species. We performed cultures with use of a membrane
      filter technique on nonselective blood agar and found that Campylobacter species
      were the most frequent enteropathogenic bacteria: the organisms were recovered
      from 7 (16%) of 43 patients with diarrhea and 5 (3%) of 158 patients without
      diarrhea (P = .001). We isolated only one campylobacter with use of conventional
      culture techniques on selective media. Phenotypic characterization of 10
      campylobacter strains resulted in the misidentification of four isolates. C.
      upsaliensis was the most frequently isolated species, followed by C. jejuni and
      C. coli. Two strains could not be identified with the available primers. Two of
      12 Campylobacter strains were resistant to erythromycin, and two were resistant
      to ciprofloxacin. We conclude that Campylobacter species other than C. jejuni can
      frequently be detected in the stools of HIV-infected patients and that these
      organisms could be associated with diarrhea.

PMID- 9195064
TI  - Use of polymerase chain reaction assays of aqueous humor in the differential
      diagnosis of retinitis in patients infected with human immunodeficiency virus.
AB  - We performed polymerase chain reaction (PCR) for detection of cytomegalovirus
      (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), and Toxoplasma
      gondii DNA in aqueous humor from 15 patients who were infected with human
      immunodeficiency virus (HIV) and who had retinitis of unclear origin; these
      patients were selected from among 820 patients evaluated by ophthalmoscopic
      examination. On the basis of the final response to treatment, CMV, VZV, and T.
      gondii retinitis was diagnosed in 5, 2, and 4 of the 15 patients, respectively.
      No final etiologic diagnosis was reached for four patients. All 5 patients with
      CMV retinitis were CMV DNA-positive. 1 of 2 patients with VZV retinopathy were
      VZV DNA-positive, and 3 of 4 patients with T. gondii retinitis were T. gondii DNA
      positive. All PCR assays of aqueous humor from the four patients without
      infectious retinitis were negative. PCR assay of aqueous humor is helpful in the
      etiologic diagnosis of retinitis of unclear origin in HIV-infected patients.

PMID- 9195066
TI  - Diversity of Campylobacter species and its impact on patients infected with human
      immunodeficiency virus.

PMID- 9195067
TI  - Familial transmission of a serious disease--producing group A streptococcus
      clone: case reports and review.
AB  - Invasive group A streptococcus (GAS) infections are emerging diseases; however,
      person-to-person transmission of invasive GAS producing life-threatening
      infection has been observed rarely. We report a small intrafamilial cluster of
      life-threatening GAS infections. A previously healthy 47-year-old father
      developed necrotizing fasciitis of the neck. Two days later, his 16-year-old
      daughter developed streptococcal angina, pneumonia, and pleural empyema. Both
      patients had signs of streptococcal toxic shock syndrome. Pulsed field gel
      electrophoresis revealed that the M6 strains of GAS isolated from the father and
      daughter had identical patterns. Cases of person-to-person transmission of
      invasive GAS infection reported in the literature are also reviewed.

PMID- 9195068
TI  - The epidemiology of hematogenous candidiasis caused by different Candida species.
AB  - The medical records of patients with hematogenous candidiasis at M. D. Anderson
      Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed.
      There were 491 episodes of infection (6 per 1,000 admissions), 79% of which
      occurred outside the intensive care unit setting. A significant decrease in
      incidence was observed among patients with leukemia over the study period,
      together with a relative decrease in Candida albicans and Candida tropicalis
      infections and an increase in Candida krusei and possibly Candida glabrata
      infections. In the multivariate analysis, fluconazole prophylaxis provided strong
      protection against the development of C. tropicalis infection (odds ratio [OR] =
      0.08) and C. albicans infection (OR = 0.15), in comparison with protection
      against infections due to other species, but it was the single most important
      determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata
      (OR = 5.08) infections. In conclusion, there has been a substantial shift in the
      epidemiology of hematogenous candidiasis caused by different Candida species in
      recent years. Fluconazole appears to be playing a major role in this observed
      shift.

PMID- 9195069
TI  - The contribution of fluconazole to the changing epidemiology of invasive candidal
      infections.

PMID- 9195070
TI  - Comparison of treatment with imipenem vs. ceftazidime as a predisposing factor
      for nosocomial acquisition of Stenotrophomonas maltophilia: a historical cohort
      study.
AB  - Imipenem is considered to confer greater risk for the acquisition of
      Stenotrophomonas maltophilia than are other beta-lactam antibiotics. We conducted
      a historical cohort study to directly compare the risks of S. maltophilia
      acquisition in patients treated with imipenem vs. ceftazidime during a 2-year
      period; 843 hospitalizations of 759 patients treated with ceftazidime (465
      hospitalizations), imipenem (294), or both agents (84) were included.
      Acquisition, as measured by clinical detection, occurred in 24 hospitalizations.
      Rates of acquisition did not significantly differ between the imipenem and
      ceftazidime groups (3.7 vs. 7.1 cases per 10,000 patients days; P = .2). In
      contrast, patients treated with both agents had higher acquisition rates (19
      cases per 10,000 patient days; P = .002). Thus, patients treated with imipenem
      are not at significantly higher risk for S. maltophilia acquisition than those
      treated with ceftazidime. The excessive risk for patients treated with both
      agents may be related in part to longer antibiotic therapy and a longer hospital
      stay.

PMID- 9195071
TI  - Cirrhotic fever in the 1990s: a prospective study with clinical implications.
AB  - Fifty consecutive patients with fever and cirrhosis were prospectively studied to
      assess if cirrhotic fever was a true clinical entity and to determine its
      characteristics and outcome. In 20% (10) of the 50 patients, an identifiable
      source of fever or infection, was not documented (these patients were defined as
      having cirrhotic fever). The patients with cirrhotic fever were significantly
      less toxic, as indicated by lower temperature (P = .0001), tachycardia (P =
      .0005), and tachypnea (P = .05), but had fever for a longer duration (P = .009)
      than did patients with infectious fever. Patients with cirrhotic fever were
      significantly less likely to have focal signs or symptoms (P < .0001) or a portal
      of infection confirmed by culture (P = .0001), as compared with patients with
      infectious fever. Outcome (at 30-days or long-term) was not different for
      patients with cirrhotic fever vs.-patients with infectious fever or matched
      controls who did not have fever. Eight (80%) of the 10 patients with cirrhotic
      fever underwent transplantation; fever did not recur after transplantation in any
      of these patients. Thus, fever in up to 20% of the febrile patients with
      cirrhosis may be attributable to cirrhosis itself; such patients may be spared
      the ongoing diagnostic maneuvers and unnecessary trials of antibiotics.

PMID- 9195072
TI  - Disseminated bacille Calmette-Guerin disease after vaccination: case report and
      review.
AB  - The attenuated bacille Calmette-Guerin (BCG) vaccine is administered to prevent
      tuberculosis. Complications of vaccination are uncommon. We report a new case of
      disseminated BCG disease and review 27 additional cases identified from a review
      of > 5,000 reports published between 1980 and 1996. Twenty-four of the 28 total
      cases were associated with an immune deficiency, including nine cases of AIDS.
      Seventy-one percent of the cases occurred in children younger than 2 years old.
      Sixty-eight percent of the patients were male. About one-half of the patients
      were vaccinated in a developed nation, but 85% of the cases were reported from a
      developed nation. Response to therapy was poor, with an overall mortality rate of
      71%. We made two new observations. Disseminated BCG disease has historically been
      a disease of infants, but cases now occur in adults and older children coinfected
      with human immunodeficiency virus. Cases also occur after revaccination of
      individuals who were anergic following the initial administration of BCG vaccine.
      Disseminated BCG disease is an uncommon but devastating complication of
      vaccination that should be considered in the appropriate clinical setting.
      Immunocompromised infants and patients with late-stage AIDS are at greatest risk
      and respond poorly to standard therapies.

PMID- 9195073
TI  - Report on an outbreak of postinjection abscesses due to Mycobacterium abscessus,
      including management with surgery and clarithromycin therapy and comparison of
      strains by random amplified polymorphic DNA polymerase chain reaction.
AB  - An outbreak of postinjection abscesses occurred in Barranquilla, Colombia, and
      was associated with local injections of lidocaine given in a single physician's
      office. Over a 5-month period, 350 (18%) of approximately 2,000 injected patients
      developed localized cutaneous abscesses or cellulitis; of 210 abscess specimens
      that were cultured, 205 were positive for rapidly growing mycobacteria,
      subsequently identified as Mycobacterium abscessus. The source of the outbreak
      was not identified. M. abscessus could not be characterized by pulsed-field gel
      electrophoresis, but all isolates were identical in terms of drug and heavy metal
      resistance patterns and random amplified polymorphic DNA PCR profiles. We believe
      this is the first report of the use of this latter technique for investigation of
      an outbreak due to M. abscessus. Therapy with a combination of surgical excision
      and 3-6 months' administration of clarithromycin was successful for 95% of 148
      patients treated in this manner; in contrast, therapy was successful for less
      than one-third of patients treated with surgery alone or clarithromycin alone.
      This is the largest of the nine known outbreaks of postinjection abscesses that
      have occurred due to rapidly growing mycobacteria and is the first in which an
      effective method of therapy was demonstrated.

PMID- 9195074
TI  - Nocardiosis after bone marrow transplantation: a retrospective study.
AB  - To evaluate the spectrum of nocardiosis after marrow transplantation, we reviewed
      the medical records of 27 patients with nocardiosis who were treated at three
      centers, and we reviewed the findings of three cases reported in the literature.
      Nocardial involvement was defined as invasive nocardiosis (n = 25), colonization
      (n = 4), or contamination (n = 1). The median time to the diagnosis of
      nocardiosis after marrow transplantation was 210 days. Nocardia asteroides
      complex accounted for 96% of isolates. All 25 invasive infections occurred in
      allogeneic marrow recipients. Ten (40%) of 25 patients with invasive nocardiosis
      were receiving double-strength oral trimethoprimsulfamethoxazole twice weekly as
      prophylaxis for Pneumocystis carinii pneumonia. Treatment regimens for
      nocardiosis included sulfonamides; synergistic agents were also often added. The
      overall survival rate at 6 years was 34%; survival from the infection itself was
      84%. Two of four nocardiosis-related deaths also involved other pathogens. The
      incidence of nocardiosis among allogeneic marrow recipients averaged 0.3% over 25
      years. We conclude that nocardiosis is a rare infection that occurs later after
      marrow transplantation than other infections and that is marginally associated
      with increased mortality among long-term survivors of allogeneic marrow
      transplantation.

PMID- 9195075
TI  - Use of amplification and sequencing of the 16S rRNA gene to diagnose Mycoplasma
      pneumoniae osteomyelitis in a patient with hypogammaglobulinemia.
AB  - A splenectomized patient with hypogammaglobulinemia who was hospitalized because
      of a high-grade fever subsequently developed osteomyelitis. Although pus cultures
      were repeatedly sterile, polymerase chain reaction (PCR) analysis with use of 16S
      rRNA gene primers with a broad specificity detected bacterial DNA in pus samples.
      Subsequent nucleotide base determination of the amplified DNA demonstrated that
      the detected DNA was derived from Mycoplasma pneumoniae. The results were
      confirmed by a PCR assay with use of M. pneumoniae-specific primers. Our findings
      confirm the usefulness of 16S rRNA gene amplification and analysis in the rapid
      and specific diagnosis of infectious osteomyelitis and reaffirm the role of such
      methods in detecting fastidious or uncultivable pathogens.

PMID- 9195076
TI  - Pneumococcal bacteremia in hospitalized Israeli adults: epidemiology and
      resistance to penicillin. Israeli Adult Pneumococcal Bacteremia Group.
AB  - In April 1993 a national survey of pneumococcal bacteremia in hospitalized
      Israeli adults was started, and this survey covered 23 of the 24 Israeli medical
      centers. During the first 2 years, 603 episodes of pneumococcal bacteremia were
      recorded. The overall annual incidence of pneumococcal bacteremia in Israeli
      adults was 14.5 episodes per 100,000 inhabitants, and the overall mortality rate
      was 27.8%. Pneumonia was the source of bacteremia in 70.8% of cases, primary
      bacteremia was the source in 17.5%, meningitis was the source in 7.5%, and otitis
      media/sinusitis was the source in 4.2%. Of the 258 pneumococcal isolates for
      which an MIC was determined, 88.8% were susceptible to penicillin, 9.3% were
      partially resistant, and only 1.9% were highly resistant. Twenty-four serogroups
      were identified from 398 strains tested. The highest percentage of penicillin
      resistant strains belonged to serogroups 23, 19, 9, 4, and 6. Although only 13 of
      these 24 serogroups correspond to the serotypes included in the 23-valent
      pneumococcal vaccine, they accounted for 94% of all isolates.

PMID- 9195077
TI  - Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of
      urine samples from patients with endemic mycoses.
AB  - We evaluated cross-reactivity in the antigen assay used for the diagnosis of
      histoplasmosis by testing urine samples from patients with disseminated fungal
      infections. The mycoses chosen for this study were selected on the basis of the
      observation that during clinical testing, cross-reactions may occur between
      Histoplasma capsulatum var. capsulatum, Paracoccidioides brasiliensis,
      Blastomyces dermatitidis, Coccidioides immitis, and Penicillium marneffei. We
      detected antigen in 12 of 19 patients with blastomycosis, 8 of 9 with
      paracoccidioidomycois, in 17 of 18 with P. marneffei infection, and in one with
      disseminated H. capsulatum var. duboisii infection. Cross-reactions were not
      observed in the assays for six patients with disseminated coccidioidomycosis.
      Cross-reactivity between the agents of other endemic mycoses should be considered
      in interpreting a positive H. capsulatum var. capsulatum antigen assay. Antigen
      detection may provide a rapid, provisional diagnosis for patients with serious
      infections caused by one of these organisms.

PMID- 9195078
TI  - Infectious ocular complications in orthotopic liver transplant patients.
AB  - We report the frequency and type of infectious ocular complications following
      orthotopic liver transplantation (OLT) and review diagnostic and therapeutic
      strategies. During the period September 1988 through November 1994, 684 patients
      underwent OLT at Mount Sinai Hospital (New York). Nine orthotopic liver
      transplant patients (1.3%) developed ocular infections: Candida albicans
      endophthalmitis (2), Aspergillus fumigatus endophthalmitis (1), cytomegalovirus
      retinitis (4), herpes simplex virus keratitis (1), and varicella-zoster virus
      panophthalmitis (1). The mean time from OLT to ocular symptoms was 42 days for
      patients with fungal infections and 128 days for patients with viral infections.
      Blurred vision was the commonest symptom (five of nine cases). The mean duration
      of follow-up was 2 years (range, 33 days to 5 years). Permanent loss of vision
      occurred in three patients, five had improvement in visual acuity, and one died
      of disseminated aspergillosis 33 days after OLT. Infectious ocular complications
      following OLT may occur as isolated events or with disseminated disease. Fungal
      infections occur earlier (mean, 42 days after OLT) than viral infections (mean, 4
      months after OLT). The clinical presentation may be atypical; aggressive
      vitreoretinal procedures and serial examinations may be required to establish the
      diagnosis. Cytomegalovirus retinitis in orthotopic liver transplant patients may
      not require life-long maintenance therapy with antiviral agents.

PMID- 9195079
TI  - Invasive mold sinusitis: 17 cases in immunocompromised patients and review of the
      literature.
AB  - A 10-year retrospective analysis of invasive mold infections in hospitalized
      patients was performed to characterize the epidemiology and clinical features of
      invasive fungal sinusitis. Seventeen cases of invasive mold sinusitis were
      identified. Eleven cases were caused by Aspergillus flavus, three were caused by
      unspecified species, and one each was caused by Aspergillus fumigatus, Rhizopus
      species, and Alternaria species, respectively. Fifteen patients had hematologic
      malignancies, and two had end-stage liver disease. The most common presenting
      symptom was periorbital swelling (seven patients). Sinusitis was diagnosed a
      median of 19 days after admission. Eight patients (47%) survived; six of these
      patients were treated with both amphotericin B and surgery. Postmortem
      examination of six patients showed evidence of disseminated disease; the brain
      was the most common extrapulmonary site (four patients). To our knowledge, this
      is the largest currently reported series on invasive mold sinusitis; our report
      extends the information on invasive mold sinusitis and shows that aggressive
      therapeutic and surgical interventions are needed to prevent rapid progression of
      disease in immunocompromised patients.

PMID- 9195080
TI  - An assessment of the usefulness of the Duke criteria for diagnosing active
      infective endocarditis.
AB  - We evaluated the usefulness of the Duke criteria for diagnosing cases of active
      infective endocarditis (IE). Patients were identified prospectively over a 3-year
      period at 54 hospitals in the Philadelphia metropolitan area. Three of us
      independently reviewed abstracted hospital records and classified 410 patients as
      definite, probable, or possible cases of IE or as probable noncases. We then
      applied the Duke criteria to this sample to assess the degree of agreement
      between our diagnoses and the diagnoses based on these new criteria. Agreement
      was good to excellent, ranging from 72% to 90%, depending on the case definition
      used. The sensitivity of the Duke criteria was also good to excellent, varying
      from 71% to 99%, again depending on case definition used. Specificity was lower
      (0-89%). We conclude that use of the Duke criteria will result in little
      underdiagnosis of IE but that it may result in overdiagnosis of IE; therefore,
      these criteria should be applied prospectively to determine their clinical
      usefulness.

PMID- 9195081
TI  - Fulminant hepatitis during herpes simplex virus infection in apparently
      immunocompetent adults: report of two cases and review of the literature.
AB  - Two apparently immunocompetent adult patients developed acute fulminant hepatitis
      during presumptive primary herpes simplex virus type 1 (HSV-1) infection without
      any visible mucocutaneous lesions. HSV hepatitis was not suspected in the case of
      patient 1, who died without treatment. Patient 2 was empirically treated with
      acyclovir because of the triad of high fever, leukopenia, and markedly elevated
      levels of aminotransferases, and this patient survived. Most immunocompetent
      patients with fulminant HSV hepatitis do not have visible mucocutaneous ulcers,
      and HSV is frequently not considered as a cause of acute hepatitis. In summary,
      fulminant hepatitis can occur during HSV infections, the diagnosis is frequently
      missed or delayed because of the absence of mucocutaneous ulcerations, and
      patients who receive early empirical treatment with acyclovir can survive this
      illness.

PMID- 9195082
TI  - Prospective study of histoplasmosis in patients infected with human
      immunodeficiency virus: incidence, risk factors, and pathophysiology.
AB  - Histoplasmosis is a common opportunistic infection in patients with human
      immunodeficiency virus (HIV) infection who reside in areas where Histoplasma
      capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV
      Infected patients in Kansas City from October 1990 through March 1993 to define
      the incidence-specific risk factors, and pathophysiology of histoplasmosis. The
      annual incidence of histoplasmosis was 4.7%; 74% of the patients with
      histoplasmosis were symptomatic (all of whom had disseminated disease). A history
      of exposure to chicken coops, a positive baseline serology for complement-fixing
      antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count
      of < 150/microL were associated with an increased risk for histoplasmosis.
      Histoplasmin reactivity and the presence of pulmonary calcifications were not
      useful markers for patients at high risk. Symptomatic infection occurred in 9.9%
      of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients
      without documented prior exposure, and in 3.0% of patients who were anergic;
      these findings suggest that the pathophysiology of histoplasmosis in patients
      with AIDS involves reactivation of latent infection in some cases and
      dissemination of exogenously acquired infection in other cases.

PMID- 9195083
TI  - Oropharyngeal candidiasis in patients with AIDS: randomized comparison of
      fluconazole versus nystatin oral suspensions.
AB  - A total of 167 human immunodeficiency virus (HIV)-infected patients with
      oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy
      with liquid suspension fluconazole (100 mg once daily) or liquid nystatin
      (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients
      were clinically cured, as opposed to 52% in the nystatin-treated group (P <
      .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a
      6% eradication rate with nystatin (P < .001). The fluconazole group had fewer
      relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This
      relapse difference no longer existed by day 42. Fluconazole oral suspension as a
      systemic therapy was more effective than liquid nystatin as a topical therapy in
      the treatment of oral candidiasis in HIV-infected patients and provided a longer
      disease-free interval before relapse.

PMID- 9195084
TI  - Use and effectiveness of hypothermia blankets for febrile patients in the
      intensive care unit.
AB  - We performed a prospective observational (noninterventional) study of hypothermia
      blanket use in a population of adult intensive care unit patients with body
      temperatures of > or = 102.5 degrees F. Thirty-nine of ninety-four febrile
      episodes (in 83 patients) were treated with hypothermia blankets. Logistic
      regression revealed that the strongest independent predictors of hypothermia
      blanket use were a temperature of > or = 103.5 degrees F (odds ratio [OR] = 17),
      mechanical ventilation (OR = 25), and acute central nervous system illness (OR =
      7.5). Hospitalization in the medical intensive care unit was strongly associated
      with avoidance of this therapy (OR = 0.023). Treatment with a hypothermia blanket
      was ordered by a physician in only 15% of cases. The mean cooling rate was the
      same (0.028 degree F/h) for blanket-treated and control patients. Multivariate
      Cox regression and factorial and repeated measures of analysis of variance
      revealed that blanket treatment was not more effective than other cooling
      methods. However, this treatment was associated with more "zigzag" temperature
      fluctuations of > or = 3 degrees F (56% of blanket-treated patients vs. 18% of
      control patients; P < .001) and rebound hypothermia (18% vs. 0; P = .001).
      Hypothermia blanket therapy is primarily a nursing decision. We conclude that in
      addition to being no more effective than other cooling measures, hypothermia
      blanket therapy was associated with more temperature fluctuations and with more
      episodes of rebound hypothermia.

PMID- 9195085
TI  - Assaulting a physiological response.

PMID- 9195086
TI  - Bacteremia due to Klebsiella oxytoca: clinical features of patients and
      antimicrobial susceptibilities of the isolates.
AB  - Forty-three patients with Klebsiella oxytoca bacteremia were seen between July
      1980 and June 1996 at National Taiwan University Hospital (Taipei, Taiwan). We
      retrospectively analyzed the clinical features of these patients and the
      antimicrobial susceptibilities of the 43 isolates recovered from them. Twenty
      seven patients (63%) had community-acquired bacteremia, and 16 patients (37%) had
      polymicrobial bacteremia. The clinical syndromes included hepatobiliary
      infections (58% of patients), primary bacteremia (23%), intravascular device
      associated infections (7%), urinary tract infections (5%), skin and soft-tissue
      infections (5%), and peritonitis (2%). Most of these patients (93%) had
      underlying diseases including hepatobiliary diseases (53%), neoplastic diseases
      (42%), and diabetes mellitus (16%). Eight patients (19%) had septic shock, and
      two (5%) had disseminated intravascular coagulation. Four patients (9%) died of
      K. oxytoca bacteremia. All isolates were susceptible to ampicillin/sulbactam,
      cefmetazole, imipenem, aminoglycosides, and quinolones, and 86% of the isolates
      were susceptible to cefazolin.

PMID- 9195087
TI  - Adverse reactions to thalidomide in patients infected with human immunodeficiency
      virus.
AB  - Thalidomide is emerging as a useful agent in the management of several
      complications of disease due to human immunodeficiency virus (HIV). We conducted
      three prospective studies of 56 HIV-infected patients who were treated with
      thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing
      to adverse reactions. Cutaneous and/or febrile reactions were the most frequent
      toxicities, arising in 20 (36%) of the patients. These reactions occurred after a
      mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly
      lower CD4 T lymphocyte counts in reactors than in nonreactors (median count,
      52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged
      patients experienced accelerated hypersensitivity; hypotension occurred in one
      case. Although sedation was an almost universal side effect among the patients,
      it was moderate or severe in only seven (13%); constipation was moderate or
      severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes
      were each noted in two (4%) of the 56 patients. We conclude that the increasing
      use of thalidomide to treat HIV-infected patients must be accompanied by
      recognition of the drug's increased potential for toxicity in this population.

PMID- 9195088
TI  - Broad-spectrum bacterial rDNA polymerase chain reaction assay for detecting
      amniotic fluid infection among women in premature labor.
AB  - We amplified bacterial 16S rRNA encoding DNA (rDNA) with the polymerase chain
      reaction (PCR) to detect amniotic fluid infection in 69 women in premature labor
      whose membranes were intact. Bacterial rDNA was detected by PCR in samples from
      15 (94%) of 16 patients with positive amniotic fluid cultures. Bacteria were
      detected by PCR in samples from 5 (36%) of 14 patients with negative cultures and
      elevated interleukin (IL)-6 levels vs. 1 (3%) of 39 patients with negative
      cultures and IL-6 levels of < or = 2,000 pg/mL (P < .01). The median amniotic
      fluid cytokine levels and the pregnancy outcomes were similar for patients with
      positive amniotic fluid cultures and those with negative cultures and positive
      rDNA PCR assays. The association between amniotic fluid infection and premature
      labor may be underestimated on the basis of amniotic fluid culture results. The
      broad-spectrum bacterial 16S rDNA PCR assay may prove useful for diagnosing
      amniotic fluid infection.

PMID- 9195089
TI  - Mycobacterium kansasii disease in patients infected with human immunodeficiency
      virus.
AB  - We evaluated the presenting characteristics, response to therapy, and outcome for
      46 patients infected with Mycobacterium kansasii and human immunodeficiency virus
      (HIV). M. kansasii infection occurred late in HIV disease (mean CD4 lymphocyte
      count, 52.4/mm3), when most patients had already developed AIDS; 91.3% of the
      patients had pulmonary involvement, and 21.7% had disseminated disease. Clinical
      and radiographic findings were consistent with pulmonary disease and had been
      present for approximately 4 weeks. Fourteen of the treated patients had disease
      that resolved or abated (mean survival +/- SE, 73.7 weeks +/- 14.6 weeks), and 13
      had disease that persisted unchanged or worsened (mean survival +/- SE, 57.3 +/-
      15.8 weeks). The outcome was poor for 17 patients who did not receive effective
      therapy (mean survival +/- SE, 14.1 +/- 5.3 weeks). M. kansasii infection
      presents late in the course of HIV disease, and the lung is the organ most
      frequently involved. Survival is clearly influenced by therapy, and even patients
      who respond poorly to therapy survive longer than those who are not treated.

PMID- 9195090
TI  - Measurement of procalcitonin levels in children with bacterial or viral
      meningitis.
AB  - We measured the plasma procalcitonin levels in 59 children who were admitted to
      the hospital because of bacterial or viral meningitis. Eighteen children with
      acute bacterial meningitis had elevated procalcitonin levels (mean level, 54.5
      micrograms/L; range, 4.8-110 micrograms/L). The procalcitonin levels in 41
      children with viral meningitis were low (mean level, 0.32 micrograms/L; range, 0
      1.7 micrograms/L; P < .0001). Assay of cerebrospinal fluid (CSF) cells and
      proteins and serum C-reactive protein showed a zone of overlapping values between
      the two groups. Procalcitonin was not produced in CSF. Plasma procalcitonin
      levels decreased rapidly during antibiotic therapy. These data suggest that the
      measurement of plasma procalcitonin might be of value in the differential
      diagnosis of meningitis due to either bacteria or viruses.

PMID- 9195091
TI  - An outbreak of Enterobacter hormaechei infection and colonization in an intensive
      care nursery.
AB  - Enterobacter hormaechei was first identified as a unique species in 1989. Between
      29 November 1992 and 17 March 1993, an outbreak of E. hormaechei occurred among
      premature infants in the intensive care nursery (ICN) at The Hospital of the
      University of Pennsylvania. The 10 infants whose cultures were positive for E.
      hormaechei (six were infected and four were colonized) had a lower median
      estimated gestational age and birth weight than did other ICN infants; other risk
      factors for infection or colonization with E. hormaechei were not identified.
      Cultures from three isolettes and a doorknob in the ICN were positive for E.
      hormaechei. Pulsed-field gel electrophoresis of isolates from six patients and
      two isolettes were identical. Observations of health care workers revealed breaks
      in infection control techniques that may have allowed transmission of this
      organism. We found that E. hormaechei is a nosocomial pathogen that can infect
      vulnerable hospitalized patients and that can be transmitted from patient to
      patient when infection control techniques are inadequate.

PMID- 9195092
TI  - Systemic infection with Mycobacterium genavense following immunosuppressive
      therapy in a patient who was seronegative for human immunodeficiency virus.
AB  - We describe, to our knowledge, the first case of disseminated Mycobacterium
      genavense infection in a patient who was seronegative for human immunodeficiency
      virus. The patient, a 47-year-old woman, had been previously treated with
      immunosuppressive drugs for 9 months to control an unclassified immunologic
      disorder characterized by intermittent fever and inflammatory pulmonary, hepatic,
      and dermal infiltrates. Antemortem and postmortem examinations revealed the
      presence of numerous mycobacteria in the bone marrow, spleen, kidneys, and lungs;
      these organisms failed to grow in vitro and were identified as M. genavense by
      16S rRNA gene sequencing. This case illustrates that systemic M. genavense
      infections are not restricted to patients with AIDS but can also occur in
      otherwise immunocompromised patients.

PMID- 9195093
TI  - Clinical significance of splenic tuberculosis in patients infected with human
      immunodeficiency virus.
AB  - To assess the clinical significance of splenic tuberculosis in patients infected
      with human immunodeficiency virus (HIV) type 1, we compared 20 patients who had
      splenic tuberculosis with 20 randomly selected, HIV-infected patients with
      culture-proven tuberculosis for whom splenic involvement had been ruled out by
      ultrasonography. All of the patients were male prison inmates and intravenous
      drug users. Statistically significant differences (P < .05) were detected between
      patients with splenic involvement (median CD4+ cell count, 54/mm3) and those
      without splenic involvement (median CD4+ cell count, 92/mm3). No specific
      symptoms suggesting splenic involvement were detected in the patients with
      splenic tuberculosis. All patients received antituberculous drugs, and none of
      these patients required splenectomy. The median survival was similar in both
      groups. Splenic tuberculosis occurs in more-severely immunocompromised HIV
      infected patients, the prognosis is generally good, the clinical response to
      therapy is usually favorable, and splenectomy is rarely necessary.

PMID- 9195094
TI  - Cerebral relapse of sarcoidlike Whipple's disease.
AB  - Whipple's disease, an infection with the recently identified intracellular
      bacillus Tropheryma whippelii, is a systemic disorder that can be life
      threatening when untreated. In a few patients, the signs and symptoms of the
      disease are similar to those of sarcoidosis, and this illness is referred to as
      sarcoidlike Whipple's disease. This variant must be recognized because patients
      with sarcoidlike Whipple's disease must be treated with antibiotics instead of
      corticosteroids, which would be indicated for patients with true sarcoidosis. We
      describe a 53-year-old man who had sarcoidlike Whipple's diseases with
      polyvisceral granulomatous dissemination that was treated with procaine
      penicillin G and streptomycin followed by doxycycline. His condition initially
      improved. However, during his 4-month course of treatment he developed a cerebral
      relapse; this relapse was successfully treated with ceftriaxone and cefixime.

PMID- 9195095
TI  - Clinical profile of herpes zoster ophthalmicus in Ethiopians.
AB  - We conducted a prospective study of 100 consecutive Ethiopian patients with
      herpes zoster ophthalmicus (HZO); this study revealed a high incidence of HZO
      among the young (mean age, 35 years). Eighty-one (95%) of 85 patients who
      underwent serological testing were seropositive for antibodies to human
      immunodeficiency virus (HIV). Unlike previous investigators, we found a marked
      increase in the incidence and severity of eyelid (25%) and ocular (78%)
      complications as well as postherpetic neuralgia (55%). Visual loss occurred in
      56% of the cases. Lack of medication, delay in presentation, severity of HIV
      related HZO, and application of herbal medications adversely affected the
      outcomes for these patients. We conclude that all patients with HZO, especially
      those younger than 45 years of age, should be screened for HIV infection. Because
      HZO is a vision-threatening problem, all health care workers should become aware
      of its management.

PMID- 9195096
TI  - Acyclovir therapy for immunocompetent children with chickenpox. Acyclovir
      chickenpox Italian Study Group.

PMID- 9195097
TI  - Rifampin-resistant Mycobacterium kansasii infection in a patient with AIDS who
      was receiving rifabutin.

PMID- 9195098
TI  - Hafnia alvei infection after liver transplantation.

PMID- 9195099
TI  - Asymptomatic hepatitis in persons who received alternative preventive therapy
      with pyrazinamide and ofloxacin.

PMID- 9195100
TI  - Pneumocystis carinii Pneumonia in Asians and Pacific Islanders.

PMID- 9195101
TI  - Tsukamurella inchonensis bacteremia in a patient who ingested Hydrochloric acid.

PMID- 9195102
TI  - Clinical significance of staphylococcus aureus bacteriuria without concurrent
      bacteremia.

PMID- 9195103
TI  - Serendipitous detection of persistent Campylobacter jejuni subspecies jejuni
      bacteremia in a patient undergoing bone marrow transplantation.

PMID- 9195104
TI  - Streptococcus constellatus endocarditis presenting as acute embolic stroke.

PMID- 9195105
TI  - Community-acquired prosthetic valve endocarditis due to methicillin-resistant
      Staphylococcus aureus.

PMID- 9195106
TI  - Cutaneous Mycobacterium avium complex infection at an intramuscular injection
      site in a patient with AIDS.

PMID- 9195107
TI  - Severe recalcitrant erythematous desquamating disorder associated with fatal
      recurrent toxic shock syndrome in a patient without AIDS.

PMID- 9195108
TI  - Detection of a 130-kD matrix metalloproteinase in cerebrospinal fluid from a
      patient with Lyme neuroborreliosis.

PMID- 9195109
TI  - Shiga toxin-producing Escherichia coli serotype OX3:H21 as a cause of hemolytic
      uremic syndrome.

PMID- 9195110
TI  - Dermonodular and visceral leishmaniasis due to Leishmania infantum with a new
      isoenzyme pattern.

PMID- 9195111
TI  - Hematogenous infections of subdural hematomas.

PMID- 9195112
TI  - Funguria might not be so benign.

PMID- 9195113
TI  - Cardiac arrhythmias associated with coadministration of azole compounds and
      cisapride.

PMID- 9195114
TI  - Pharmacokinetic evaluation of herbal remedies. Basic introduction, applicability,
      current status and regulatory needs.

PMID- 9195118
TI  - Accidental metronidazole overdose in a preterm newborn.

PMID- 9195115
TI  - Clinical pharmacokinetics of sulindac. A dynamic old drug.
AB  - Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the indene acetic
      acid class. The absorption of sulindac is rapid when given orally. Sulindac is
      reversibly metabolised to sulindac sulphide which has anti-inflammatory and
      analgesic properties and is irreversibly metabolised to sulindac sulphone which
      has been suggested to possess antiproliferative effects against tumours. Sulindac
      and its sulphide and sulphone metabolites bind extensively to plasma albumin.
      Sulindac is eliminated following bio-transformation; sulindac and sulindac
      sulphone and their respective glucurooconjugated metabolites are excreted in
      urine; however only a small amount of the sulindac sulphide metabolite is
      eliminated in urine. Following long term twice daily administration both sulindac
      and its metabolites accumulate in plasma. Both patients with cirrhosis and the
      elderly demonstrate elevated concentrations of all species upon long term
      sulindac administration as compared with a single dose. The disposition of
      sulindac and its metabolites may be tied to renal function. In end-stage renal
      disease, increased free fractions of all species and accumulation of the sulphide
      and sulphone metabolites, and to a lesser extent sulindac, occurs. Significant
      drug interactions have been demonstrated for dimethylsulphoxide, cyclosporin,
      furosemide (frusemide), hydrochlorothiazide, methotrexate and cholestyramine.

PMID- 9195116
TI  - Fosinopril. Clinical pharmacokinetics and clinical potential.
AB  - Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting
      enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa
      and liver to the active diacid, fosinoprilat, which has unique pharmacological
      properties. The majority of the active moieties of other ACE inhibitors are
      excreted in the urine. This means that an adjustment in either the dosage and/or
      the administration interval is needed in patients with moderate to severe renal
      dysfunction, in order to reduce drug accumulation and the possibility of an
      excessive decrease in blood pressure or other adverse effects. On the other hand,
      fosinoprilat is excreted both in urine and bile (as with temocaprilat,
      zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or
      administration interval may be unnecessary in patients with moderate to severe
      renal dysfunction, as impaired renal function influences little of the
      pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests
      that the pharmacokinetic variables of fosinoprilat in patients receiving
      haemodialysis were similar to those in patients with moderate to severe renal
      dysfunction. Dosage modifications or supplemental dose administration following
      dialysis may be unnecessary. The hypotensive effect of the combination of
      fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with
      fosinopril are unlikely in patients receiving thiazide or loop diuretics.
      Fosinopril has beneficial effects for patients with hypertension and left
      ventricular hypertrophy because it produces an adequate reduction in blood
      pressure and reversal of left ventricular hypertrophy. There are a large number
      of studies of the pharmacokinetics of fosinopril. However studies of its
      pharmacokinetic drug interactions with other drugs are far fewer. Further
      investigations are needed in several clinical settings.

PMID- 9195119
TI  - General medicine update: NIDDM, prevention of CAD, & risks & benefits of hormone
      replacement therapy.

PMID- 9195117
TI  - Cyclosporin pharmacokinetics in paediatric transplant recipients.
AB  - Cyclosporin is an essential component of the antirejection drug protocol used in
      the long term management of paediatric organ transplant recipients. This article
      looks at the pharmacokinetics of cyclosporin in paediatric kidney, heart, liver
      and bone marrow transplant recipients and critically evaluates its relationship
      to pharmacokinetic data in adult transplant recipients. There are limited data on
      the pharmacokinetics of cyclosporin in paediatric transplant recipients (14
      publications provide the database) as compared with the adult transplant
      population. Study design, analytical methodology and age ranges of the
      individuals differ between studies, making comparative interpretation of
      pharmacokinetic data difficult. However, significant trends are noteworthy and
      these may influence dose administration guidelines and therapeutic monitoring
      standards for cyclosporin in the paediatric organ transplant recipient. The
      bioavailability of the oral formulations of cyclosporin is highly variable as
      with the adult population, but there appears to be a correlation between
      cyclosporin bioavailability and age with both the traditional oral formulation
      (Sandimmun) and the new microemulsion formulation (Neoral) in young liver
      transplant patients. Bowel length, presystemic metabolism in the gut wall, type
      of transplant and time since transplant are contributing factors in the variation
      of bioavailability patterns in paediatric transplant patients. The volume of
      distribution of cyclosporin does not appear to differ between paediatric and
      adult transplant recipients, but systemic clearance is comparatively higher in
      the paediatric population. In general, paediatric patients require higher doses
      of cyclosporin to achieve target blood concentrations of the drug which are
      equivalent to the values used in the adult population. Younger patients (less
      than 8 years of age) may be managed more effectively with a 3 times daily
      administration schedule rather than the twice daily schedule which is universally
      used for cyclosporin in the transplant population. The comparatively higher doses
      and more frequent administration schedule used in paediatric transplant
      recipients are the consequence of age-related differences in bioavailability and
      the possibility of increased metabolic clearance of the drug in younger patients.

PMID- 9195120
TI  - Mycobacterial infections: new threats from old disease.

PMID- 9195121
TI  - Pheochromocytoma: issues in diagnosis & treatment.

PMID- 9195122
TI  - Prospective 6-month, double-blind trial of hydroxychloroquine treatment of CPDD.

PMID- 9195123
TI  - Low back pain.

PMID- 9195124
TI  - Pediatric & adolescent gynecology.

PMID- 9195125
TI  - Controversies in cost-effective imaging: a primer for physicians & utilization
      managers.

PMID- 9195126
TI  - Gastrointestinal disorders in the elderly.

PMID- 9195127
TI  - Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR
      antigens expressed on B cells.
AB  - The regulation of NF-kappa B activation following the triggering of HLA-DR
      antigens by mAb L243 has been studied at various times in Raji cells.
      Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa
      B DNA binding after triggering of HLA-DR antigens. Using TNF-alpha-activity
      neutralizing antibodies, the authors demonstrated that the upregulation of NF
      kappa B was found to depend, at later time point, on an autocrine effect of TNF
      alpha secreted following triggering of HLA-DR antigens. In contrast, it was found
      to be TNF-alpha independent in the early time point. Moreover, the upregulation
      of NF-kappa B binding activity is regulated by the triggering of selected
      epitopes of HLA-DR antigens. In fact, mAb L243 but not the staphylococcal
      superantigens, staphylococcal exotoxin toxic shock syndrome toxin-I or
      staphylococcal enterotoxin B, regulate the NF-kappa B binding activity.

PMID- 9195128
TI  - Differential effects of IL-6 on systemic and central production of TNF: a study
      with IL-6-deficient mice.
AB  - Interleukin 6 (IL-6) is known to inhibit the synthesis of tumour necrosis factor
      (TNF) in vitro and in vivo. In this study we investigated the possible role of IL
      6 as an endogenous inhibitor of TNF production in the brain or in the periphery
      using IL-6-deficient mice or administering recombinant human IL-6 (rhIL-6). When
      IL-6-deficient mice were injected intracerebroventricularly (i.c.v.) with
      lipopolysaccaride (LPS), no differences were observed in the production of TNF in
      the brain, while in the periphery (serum or spleen) TNF levels were markedly
      increased (about four-fold). When normal mice were injected i.c.v. with a
      combination of LPS and rhIL-6, inhibition of TNF production was only slight
      (about 20%), while IL-6 had a stronger effect (> 80% inhibition) in the
      periphery. Co-administration of soluble IL-6 receptor (sIL-6R) did not enhance
      the effect of IL-6 on brain TNF, so this refractoriness cannot be attributed to a
      lack of IL-6 receptors. Interestingly, IL-6 potently inhibited LPS-induced TNF
      production by macrophagic cells but not by a microglial cell clone, suggesting
      that the defective response to IL-6 of the brain lies within the responsiveness
      TNF producing cells to IL-6. It thus appears that the TNF-inhibitory role of IL-6
      is confined to the periphery.

PMID- 9195129
TI  - Detection and characterization of IL-1 receptor antagonist in tissues from
      healthy rabbits: IL-1 receptor antagonist is probably involved in health.
AB  - Interleukin 1 (IL-1) is postulated to function in maintaining homeostasis,
      however, over-action of this cytokine may lead to disruption of homeostasis due
      to it's wide spectrum of activities. To understand the endogenous regulation of
      this cytokine, we examined the existence of IL-1 receptor antagonist (IL-1Ra) in
      tissues from healthy rabbits. IL-1Ra was constitutively produced in all tissues
      examined (lung, liver, spleen, thymus, caecum, skin, kidney, heart, and brain),
      as estimated by ELISA. Immunoprecipitation, RT-PCR and immunohistochemical
      studies indicated that all tissues produced secreted form of IL-1Ra (sIL-1Ra),
      whereas thymus, caecum, skin and kidney produced both sIL-1Ra and intracellular
      of IL-1Ra. All tissue IL-1Ra purified using anti-IL-1Ra IgG affinity
      chromatography had inhibitory activity on the IL-1-induced thymocyte
      proliferative response, and the activity was totally abolished by anti-IL-1Ra
      mAb. No IL-1 activity was detected in any tissues except skin and heart, however,
      after preincubation of the samples with anti-IL-1Ra, the activity was first
      visible in the tissues. Under these conditions, IL-1 activity in skin and heart
      was enhanced to 170% and 280%, respectively. Taken together, we conclude that
      tissue IL-1Ra is involved in health maintenance by masking co-existing IL-1
      activity present in tissues.

PMID- 9195131
TI  - Sarcoma cells engineered to secrete IFN-gamma or IL-2 acquire sensitization to
      immune cell killing via different mechanisms.
AB  - The murine fibrosarcoma FS29 can be more efficiently killed by syngeneic
      lymphocytes when it has been engineered to secrete either interferon gamma (IFN
      gamma), or interleukin 2 (IL-2). The mechanisms by which the two cytokines
      enhance target sensitivity differ. Supernatant from IFN-gamma-secreting cells can
      enhance the sensitivity of unmodified cells. The enhanced sensitivity correlates
      with MHC upregulation observed on both the IFN-gamma-secreting and supernatant
      treated cells. In contrast, supernatant from IL-2-secreting cells does not affect
      the sensitivity of unmodified cells. IL-2 can be detected, by a bioassay, bound
      to the extracellular matrix of the secreting tumour cells.

PMID- 9195130
TI  - Alteration of the CD34+ Tf-1 beta cell line profile in response to long-term
      exposure to IL-15.
AB  - Interleukin 15 (IL-15) is a cytokine with many functional characteristics that
      are similar to IL-2. Most of the functional activities that IL-2 and IL-15
      support have been evaluated in short-term assays. It was our intention, then, to
      determine the long-term effects of IL-15 in comparison to IL-2. These studies
      were performed using the growth factor-dependent myelomonocytic cell line, Tf-1,
      which has been well characterized with regard to morphology, CD marker
      expression, responses to certain growth factors and cytokines (GM-CSF, IL-4,
      erythropoietin), and can differentiate through the myeloid and erythroid
      lineages. In order to study IL-2 and IL-15 responses, Tf-1 cells were
      retrovirally infected with the IL-2R beta chain gene as a means to confer IL-2
      responsiveness to this cell type. The results of this study demonstrate that
      retroviral infection of Tf-1 successfully generated a stable IL-2 responsive cell
      line, Tf-1 beta, without interfering with the original characteristics of the Tf
      1 cell. Tf-1 beta cells respond functionally to both IL-2 and IL-15. When Tf-1
      beta cells are grown for 8 weeks in IL-2 (Tf-1 beta 2), rather than GM-CSF, the
      original morphology, CD marker expression, esterase activity and proliferative
      response is unaltered in comparison to that of the original Tf-1 beta line
      maintained in GM-CSF. However, long-term growth of Tf-1 beta in IL-15 (Tf-1 beta
      15) results in morphological alterations, downregulation of CD33, CD38, and HLA
      DR, and a decreased response to IL-15 in comparison to Tf-1 beta 2. These studies
      support the concept that retroviral infection, even when it confers new functions
      upon a cell, does not necessarily alter all other functions, as assessed by
      evaluation of its phenotypic profile. Furthermore, the production of the Tf-1
      beta 2 and Tf-1 beta 15 sublines demonstrates that IL-2 and IL-15 can support
      long-term cell growth. However, this long-term growth in IL-15 leads to subtle
      alterations in the cell profile that are not seen with IL-2, suggesting that
      distinctions in IL-2 and IL-15 function do exist. Further study of the Tf-1 beta
      15 cell line will be useful to clarify these functional distinctions between IL-2
      and IL-15.

PMID- 9195132
TI  - Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2
      integrin dependent homotypic adhesion in human CD4+ T cell lines.
AB  - Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2)
      induces beta 2-integrin mediated adhesion, migration, and extravasation of T
      lymphocytes. It is, however, largely unknown how IL-2 receptors (IL-2R) are
      coupled to the beta 2-integrin adhesion pathway. Because IL-2 modulates enzymatic
      activity and/or subcellular distribution of serine/threonine phosphatases 1 and
      2A (PP1/PP2A) in T cells, we examined the role of these phosphatases in IL-2
      induced homotypic adhesion in antigen specific human CD4+ T cell lines. We show
      that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A activity
      and IL-2 induced adhesion, whereas cyclosporin A, an inhibitor of protein
      serine/threonine phosphatase 2B (PP2B), does not, suggesting that PP1 and/or PP2A
      are involved in IL-2 induced adhesion. Endothall, which preferentially inhibits
      PP2A, strongly inhibited cytokine induced adhesion, whereas the structurally
      related compound 1,4-dimethylendothall had no effect on either phosphatase
      activity or the adhesion response. Okadaic acid, which preferentially inhibits
      PP2A, almost completely blocked IL-2-induced adhesion, whereas tautomycin, a
      potent inhibitor of PP1, had no inhibitory effect on cytokine induced adhesion at
      concentrations which strongly inhibited phosphatase activity. In conclusion,
      these data provide evidence that PP2A plays a critical role in IL-2-induced beta
      2-integrin-dependent adhesion of human T cell lines.

PMID- 9195133
TI  - A metalloproteinase inhibitor blocks the shedding of soluble cytokine receptors
      and processing of transmembrane cytokine precursors in human monocytic cells.
AB  - A number of membrane-anchored cytokines and cytokine receptors are susceptible to
      yield soluble counterparts. Recently, peptide-hydroxamate metalloproteinase
      inhibitors have been reported to block the proteolytic processing of tumour
      necrosis factor (TNF)-alpha 55- and 75-kDa TNF receptors (TNF-R55 and TNF-R75),
      and interleukin (IL)-6R. In this report the authors studied the effect of an
      hydroxamate metalloproteinase inhibitor on the secretion of cytokines and the
      generation of cytokine soluble receptors by human myelomonoycytic cell lines and
      purified monocytes. Whereas secretion of cytokines lacking a transmembrane domain
      precursor (IL-1 alpha, IL-1 beta, IL-6 or IL-10) is either unaffected or
      augmented, shedding/secretion of transmembrane domain-containing cytokines and
      cytokine receptors [TNF-alpha, macrophage colony-stimulating factor (M-CSF),
      transforming growth factor (TGF)-alpha, stem cell factor (SCF), TNF-R55, TNF-R75,
      and IL-6R] was dramatically decreased in the presence of the metalloproteinase
      inhibitor. The diversity of sequences in the cleavage site of these proteins and
      differences found in the inhibitory concentration values suggest the existence of
      a metalloproteinase family displaying different substrate specificity. These
      results emphasize the important role of metalloproteinases as regulators of
      membrane expression and secretion of cytokines and cytokine receptors.

PMID- 9195134
TI  - Species-specific expression of type II TGF-beta receptor isoforms by articular
      chondrocytes: effect of proteoglycan depletion and aging.
AB  - Recently, a new isoform of the type II transforming growth factor beta receptor
      (TGF-beta RII) was identified. This isoform (TGF-beta RII2) contains an insertion
      of 25 amino acids in the extracellular domain of the receptor. Using RT-PCR the
      authors demonstrated that both TGF-beta RII1 and TGF-beta RII2 are expressed by
      chondrocytes in murine and human articular cartilage. Bovine articular
      chondrocytes expressed TGF-beta RII1 mRNA but did not express detectable levels
      of TGF-beta RII2 mRNA, suggesting that the new isoform does not play an important
      role in normal bovine cartilage physiology. Because TGF-beta responses seem to be
      age related and differential TGF-beta responses have been described between
      normal cartilage and cartilage undergoing repair the authors studied if the
      relative mRNA expression between these isoforms is altered during cartilage
      repair and aging. No differences in the relative mRNA expression of the two
      isoforms of the type II TGF-beta receptor could be demonstrated in murine
      cartilage during aging or during the repair phase after mild PG depletion
      indicating that it is unlikely that age-related TGF-beta responses and
      differential TGF-beta responses between normal cartilage and cartilage undergoing
      repair are the result of differences in the relative expression of the two TGF
      beta RII isoforms.

PMID- 9195135
TI  - S-methyl-L-thiocitrulline counteracts interleukin 1 beta induced suppression of
      pancreatic islet function in vitro, but does not protect against multiple low
      dose streptozotocin-induced diabetes in vivo.
AB  - Nitric oxide, induced by pancreatic islet exposure to cytokines, has been
      implicated in beta-cell destruction in insulin-dependent diabetes mellitus. In
      this context it could be worthwhile to characterize inhibitors of the nitric
      oxide generating enzyme. For this purpose rat pancreatic islets were cultured for
      48 h in medium supplemented without or with 10, 100 or 500 microM of S-methyl-L
      thiocitrulline, in the absence or presence of 25 U/ml of interleukin 1 beta (IL-1
      beta). S-methyl-L-thiocitrulline alone did not affect the islet glucose oxidation
      rate, but all concentrations of S-methyl-L-thiocitrulline prevented IL-1 beta
      induced suppression of the islet glucose metabolism. Moreover, S-methyl-L
      thiocitrulline (100 microM) completely protected against cytokine mediated
      inhibition of medium insulin accumulation, glucose-stimulated insulin release and
      (pro)insulin biosynthesis. IL-1 beta caused a more than 10-fold increase in
      medium nitrite production, an indication of nitric oxide production, which was
      blocked by S-methyl-L-thiocitrulline. Acutely in the absence of IL-1 beta, islet
      glucose-stimulated insulin release was enhanced by S-methyl-L-thiocitrulline (100
      microM). The efficacy of S-methyl-L-thiocitrulline, NG-monomethyl-L-arginine and
      aminoguanidine in counteracting IL-1 beta induced nitrite formation was also
      compared. When estimating the half-maximal inhibitory concentration for this
      effect, it was approximately 10 microM for S-methyl-L-thiocitrulline and about
      1000 microM for NG-monomethyl-L-arginine and aminoguanidine. Next, the efficacy
      of S-methyl-L-thiocitrulline was tested in an animal model of insulin-dependent
      diabetes mellitus i.e. multiple low-dose streptozotocin-induced diabetes in male
      C57BL/Ks mice (40 mg/kg body weight/day for 5 days). It was found that all groups
      of mice treated with streptozotocin injections gradually developed
      hyperglycaemia. Administration of S-methyl-L-thiocitrulline (15 mg/kg body
      weight/day) either for 6-13 days or for 5-11 days after the first STZ injection
      could not prevent this effect. Moreover, S-methyl-L-thiocitrulline did not appear
      to influence the evolution of mononuclear cell infiltration and pancreatic
      insulitis. Thus the present study shows that S-methyl-L-thiocitrulline can
      potently block cytokine induced activation of nitric oxide synthase in pancreatic
      islets, but using the presently adopted administration protocol failed to protect
      against development of insulin-dependent diabetes mellitus in vivo.

PMID- 9195136
TI  - Three types of recombinant human granulocyte colony-stimulating factor have
      equivalent biological activities in monkeys.
AB  - Three types of rhG-CSF are commercially available (non-glycosylated: filgrastim,
      glycosylated: lenograstim and N-terminal mutated: nartograstim). It has been
      reported that higher in vitro or in vivo efficacy was found in glycosylated or N
      terminal mutated rhG-CSF than in non-glycosylated rhG-CSF. We reported that
      glycosylated or N-terminal mutated rhG-CSF showed equal efficacy to non
      glycosylated rhG-CSF in vivo. In this study, we carried out a direct comparison
      of pharmacokinetics and pharmacological effects of three rhG-CSFs. We used
      commercially obtained rhG-CSF products whose activities are guaranteed by the
      manufacturers. Monkeys have been selected as the experimental animals because of
      their close relationship to humans concerning drug disposition and daily doses
      were in accordance with the clinical use of rhG-CSFs. Normal cynomolgus monkeys
      were given 1.5 or 5 micrograms/kg of rhG-CSF either intravenously or
      subcutaneously for 5 consecutive days. After intravenous injection, the serum
      concentration-time profiles of nartograstim were almost identical to those of
      filgrastim at both doses but the concentrations after lenograstim administration
      decreased faster. Following subcutaneous administration, no marked differences
      were observed between the three rhG-CSFs, although lenograstim showed lower serum
      concentrations than both filgrastim and nartograstim. In spite of some small
      differences in the pharmacokinetics of the three rhG-CSFs, the pharmacodynamics
      were identical.

PMID- 9195137
TI  - Cyclic plasma IL-6 levels during normal menstrual cycle.
AB  - Steroid hormones including sex hormones are known to influence cytokine
      production by cells in vitro. We investigated whether there are differences in
      cytokine production in vivo and ex vivo during the menstrual cycle in five
      ovulating women compared with five pregnant women and nine males. Interleukin 6
      (IL-6) in plasma changed periodically during 12 of 13 cycles in five women. The
      IL-6 levels were lowest in the luteal phase when progesterone levels were
      elevated and highest preovulatory when progesterone levels were low (P < 0.009).
      This phenomenon was unrelated to changes in haematocrit or albumin and
      independent of cortisone, growth hormone, luteinizing or follicle stimulating
      hormone and testosterone. In contrast to IL-6, the soluble IL-6 receptor did not
      vary significantly during the menstrual cycle. In comparison, nine males and five
      pregnant women had low plasma IL-6 levels comparable with women during the luteal
      phase. In addition, levels of IL-6, IL-10 and TNF were determined after whole
      blood stimulation with lipopolysaccharide ex vivo during a menstrual cycle.
      Neither the number of CD-14++ or CD14/CD16+ cells nor the amounts of IL-6, IL-10
      and TNF after stimulation showed cyclic changes. We suggest that sex hormones,
      especially oestrogen and progesterone, may influence immune responses by
      decreasing basal IL-6 levels in vivo.

PMID- 9195138
TI  - Virtual reality, disability and rehabilitation.
AB  - Virtual reality, or virtual environment computer technology, generates simulated
      objects and events with which people can interact. Existing and potential
      applications for this technology in the field of disability and rehabilitation
      are discussed. The main benefits identified for disabled people are that they can
      engage in a range of activities in a simulator relatively free from the
      limitations imposed by their disability, and they can do so in safety. Evidence
      that the knowledge and skills acquired by disabled individuals in simulated
      environments can transfer to the real world is presented. In particular, spatial
      information and life skills learned in a virtual environment have been shown to
      transfer to the real world. Applications for visually impaired people are
      discussed, and the potential for medical interventions and the assessment and
      treatment of neurological damage are considered. Finally some current limitations
      of the technology, and ethical concerns in relation to disability, are discussed.

PMID- 9195139
TI  - An evaluation of short-term group therapy for people with aphasia.
AB  - This paper reports an evaluation of a group therapy intervention conducted with
      aphasic people (n = 6). The intervention comprised 10 sessions of approximately
      90 min duration and included two participants with stuttering difficulties. The
      therapy programme consisted of communication activities within the group which
      encouraged sharing of personal experiences, videotaping of role-play activities
      for self- and group-evaluation and practice tasks completed outside the group.
      Measures of functional communicative ability, attitudes to communication and
      psychological adjustment were obtained before and after the intervention.
      Findings showed significant improvements in communicative competence and
      attitudes to communication over the course of the intervention. Before the
      intervention self-esteem and communicative competence were highly
      intercorrelated. By the end of the therapy sessions the correlation between self
      esteem and communicative competence was significantly smaller and was non
      significant. This indicates that communicative function was not related to
      feelings of self-worth by the end of the intervention. Improvements in attitude
      to communication, greater attendance and completion of assignments were each
      predictive of reduced levels of depression. There was also evidence that stronger
      beliefs about the role of personal effort in improving speech were predictive of
      improvements in communication attitudes. A measure of satisfaction showed
      extremely positive evaluation of the intervention by participants. It is
      concluded that shortterm group therapy can produce improvements in communicative
      abilities and attitudes, and have psychological benefits for participants.
      Several suggestions for future research are outlined.

PMID- 9195140
TI  - Perceptual impairment and its impact on rehabilitation outcome. SUE Study Group.
AB  - The aim of the study was to investigate the effect of perceptual assessment and
      treatment provided on a stroke unit by comparison with that provided on health
      care of the elderly and general medical wards. Stroke patients admitted to
      hospital were randomly allocated to a stroke unit or conventional wards.
      Perceptual impairment was assessed on entry to the study and at 3, 6 and 12
      months after randomization. Stroke unit patients show significantly less
      impairment of perceptual abilities at all stages after stroke. Perceptual
      impairment, as assessed using the Rey figure copy, was a significant predictor of
      outcome as assessed on the Barthel Index, Extended ADL scale and Rivermead Motor
      Assessment at 12 months after stroke.

PMID- 9195141
TI  - Implant outcomes: towards a mixed methodology for evaluating the efficacy of
      adult cochlear implant programmes.
AB  - Studies concerned with the efficacy of cochlear implants have traditionally
      focused on measuring enhancements in speech perception associated with
      implantation. This paper reports the findings of a study concerned with
      qualitative and quantitative measures of psychosocial benefit associated with the
      adult cochlear implant programme. Cochlear implants enhanced implantees'
      interpersonal communication skills and social confidence, and were associated
      with a reduction in the user's social anxiety. Broader socioeconomic gains were
      not achieved by implantees, mainly because of an absence of adequate employment
      and community education programmes associated with implant programmes.

PMID- 9195142
TI  - Membership of the University of the Third Age (U3A) and perceived well-being.
AB  - To study the perceived well-being of members of the University of the Third Age
      (U3A) a sample of 975 members with a mean age of 67.9 +/- 6.98 years (range 50
      94) was obtained from within the Greater Sydney Metropolitan Region and
      administered the Medical Outcomes Study (MOS) Short Form 36-item (SF-36) health
      survey. The SF-36 assesses eight health concepts; limitations in physical
      activities because of health problems; limitations in social activities because
      of physical or emotional problems; limitations in usual role activities because
      of physical health problems; bodily pain; general mental health; limitations in
      usual role activities because of emotional problems; vitality; and general health
      perception. Comparisons were made with USA normative peer groups, and the U3A
      sample scored as well as, or better than, their American peers. It is concluded
      that members of U3A had better-than-average general, physical and mental health,
      and that membership of U3A can, even in the very elderly, assist in conferring a
      much more positive perception of well-being.

PMID- 9195143
TI  - The need for disability awareness training among rurally based Australian general
      medical practitioners.
AB  - This project followed a needs analysis of people with disabilities living in
      rural and remote areas of New South Wales, Australia, in which consumers (people
      with disabilities and their carers or closest person) argued that there was an
      urgent need for disability awareness training for rurally based general medical
      practitioners (GPs). The project reported here explored the perceptions of
      rurally based GPs to determine whether they also perceived a need for disability
      awareness training. It also explored GPs' awareness and use of referral services
      available within their communities. Information gathered through questionnaires
      was used by a discussion group to develop recommendations. These support the need
      for disability awareness training for GPs at both undergraduate and in-service
      levels, and include strategies for providing information to rurally based
      professionals on an ongoing and regular basis in order to address the
      difficulties they experience in keeping up to date on issues associated with
      disability.

PMID- 9195144
TI  - Inhibition of experimentally induced endolymphatic hydrops by middle ear
      ventilation.
AB  - The tympanic membrane was perforated (n = 19) or a tube was inserted into the
      middle ear through the wall of the tympanic bulla (n = 6) immediately after
      blockage of the endolymphatic duct in guinea pigs. Total cochlear endolymph
      volume and volumes in each cochlear turn were determined from serial sections of
      the temporal bones and volume changes were analyzed statistically by comparison
      with hydropic controls without treatment (n = 12). Results showed that both
      middle ear ventilation procedures significantly reduced the subsequent
      development of endolymphatic hydrops. This inhibition of hydrops was presumed to
      be due to pressure release into the middle ear and/or improved oxygenation of the
      middle and inner ears. Findings suggest the possible merit of a tympanostomy as a
      treatment for Meniere's disease in carefully selected patients refractory to
      medical management.

PMID- 9195145
TI  - Prognostic value of clinical findings in histologically verified adult-onset
      laryngeal papillomas.
AB  - A retrospective study of adult-onset laryngeal papilloma was performed to clarify
      whether any clinical features at the time of diagnosis could predict its course.
      All patients had a histologically confirmed diagnosis of laryngeal papillomas and
      were treated at Helsinki University Hospital between 1975 and 1994. Those with
      adult-onset disease and follow-up exceeding 1 year (n = 74) entered the study.
      Based on the case records surveyed, results suggested two risk factors for
      frequent laryngeal procedures: young age at onset of papilloma and a lesion
      extending to the anterior third to the vocal folds. It was not possible to
      predict the course of the disease by such clinical findings as symptoms or size
      or number of primary papilloma lesions. As regards the recurrence of disease, the
      classic division of adult-onset laryngeal papilloma into solitary and multiple
      type was not found to be clinically relevant.

PMID- 9195146
TI  - Alteration of loosely bound calcium in the guinea pig organ of Corti after
      treatment with diltiazem as calcium channel blocker.
AB  - After oral administration of the organic calcium channel blocker diltiazem to
      guinea pigs for 7 days, calcium ions were precipitated with potassium antimonate
      in the cochleae. The spatial distribution of the precipitates was studied by
      energy-filtering transmission electron microscopy and the amount of the
      ultrastructural reaction products formed was determined semiquantitatively by an
      image processing system. Compared with untreated control ears, the number of the
      formed precipitates was reduced drastically in the inner hair cells after
      diltiazem treatment. In addition, electron microscopic analysis revealed that the
      number of calcium precipitates attached at the basolateral membrane of the outer
      hair cells was clearly reduced when compared with untreated control specimens. A
      large number of histochemical reaction products could be identified in the
      basilar membrane and were also observed in the untreated control specimens. The
      spatial distribution of the calcium precipitates in the lamina reticularis was
      not affected by diltiazem treatment and calcium precipitates could be identified
      within different cell membranes. The techniques used was considered to be helpful
      for identifying calcium channels ultrastructurally in intact undissected tissues
      and to support light microscopic analyses and patch-clamp electrophysiological
      measurements.

PMID- 9195147
TI  - Electron microscopic and immunomorphological investigations on the mucosa of the
      human paranasal sinuses.
AB  - The morphology of the mucosa from the human paranasal sinuses was investigated by
      electron microscopy. A total of 27 specimens was taken from 11 patients following
      midfacial fractures. All tissue samples were biopsied during surgery after
      informed consent had been given. In accordance with light microscopic
      investigations, the mucosa represented a highly prismatic epithelium consisting
      of kinocilia-carrying and mucus-producing (goblet) cells. Other cell types, such
      as those occurring in the respiratory epithelium of other areas, could not be
      demonstrated. Electron microscopic and immunomorphological investigations
      revealed collagen type VII beneath the lamina densa of the basal lamina.
      According to findings obtained to date, this collagen type accompanies only a
      multilayered epithelium. Another peculiarity was the small number of basophils
      and eosinophils. Pronounced acute reactions of the mucosa in this area cannot be
      expected, which is in contrast to that of the nasal mucosa.

PMID- 9195148
TI  - A placebo controlled study comparing the efficacy of intranasal azelastine and
      beclomethasone in the treatment of seasonal allergic rhinitis.
AB  - This study compared a new intranasal anti-allergic drug, azelastine (0.56 mg bid)
      with intranasal beclomethasone (0.2 mg bid) and placebo in the treatment of
      symptoms associated with seasonal rhinitis. After administering placebo for 3-5
      days as a "run-in" period, eligible patients were randomized to treatment for 2
      weeks: 83 patients received azelastine, 83 beclomethasone and 77 placebo. Each of
      six symptoms was assessed daily using a four-point scale. Total symptom scores
      showed that azelastine-treated patients experienced a more rapid onset of overall
      symptom relief than beclomethasone-treated patients. This was significant on day
      1 (P < 0.003) and continued until day 5. By the end of the 2-week study period,
      the beclomethasone-treated group showed greater improvement than both the
      azelastine and placebo groups (P = 0.002 and P = 0.0001, respectively). In
      contrast, visual analogue scales at this time showed no significant differences
      between the azelastine and beclomethasone treatment groups, with both groups
      demonstrating significant reductions in total symptom scores compared to placebo
      (P = 0.0004 and P = 0.0001, respectively). Differing sensitivities were found in
      the four-point scales reported by the patients and the investigators and the
      patients' visual analogue scales in the measurement of symptom severity. However,
      all three techniques confirmed that both azelastine nasal spray and
      beclomethasone nasal spray were effective treatments for seasonal rhinitis. While
      a greater improvement in overall symptoms was found for the beclamethasone
      treated patients compared to azelastine-treated patients, diary card data
      confirmed the more immediate onset of symptom relief provided by azelastine. No
      serious adverse events were found in the present study and included no complaints
      of drowsiness.

PMID- 9195149
TI  - Spasmodic laryngeal dyspnea: a rare manifestation of laryngeal dystonia.
AB  - We describe clinical experiences in the management of three patients with
      laryngopharyngeal dystonia causing severe breathing problems. In contrast to
      spasmodic dysphonia, which presents with action-induced involuntary spasm of
      laryngeal muscles during speaking, all three patients showed laryngopharyngeal
      spasms primarily during respiration. In analogy to spasmodic dysphonia we propose
      the term spasmodic laryngeal dyspnea for this rare condition. Localized
      unilateral botulinum toxin injected into the thyroarytenoid muscle and/or
      ventricular folds reduced the quantity and quality of spasms and led to a
      pronounced improvement of breathing problems.

PMID- 9195150
TI  - Synovial sarcoma of the neck.
AB  - Primary synovial sarcoma of the head and neck region is a rare tumor. This report
      describes seven cases of primary synovial sarcomas, of which two were in the
      parapharyngeal region, two in the supraclavicular region, and one each in the
      hypopharynx, sternocleidomastoid and submandibular regions. Clinical
      presentations, radiological findings, histopathology and management are reviewed.
      All patients received multimodal therapy using aggressive surgery, radiotherapy
      and chemotherapy. Five of the patients are alive and disease free after 24-108
      months of follow-up. Achievement of locoregional control appears to be the
      hallmark of successful therapy.

PMID- 9195151
TI  - Pathogenesis of non-traumatic atlanto-axial subluxation (Grisel's syndrome).
AB  - Non-traumatic atlanto-axial subluxation (AAS) is an uncommon complication of
      upper neck inflammatory processes and head and neck surgery. It is also known
      under the eponym of Grisel's syndrome (GS). We present a case report of a 6-year
      old boy with GS that resulted from a retropharyngeal abscess. A diagnosis was not
      made until 2 months after the occurrence of infection. Re-evaluation of repeated
      CT scans of the neck showed the sequential development of AAS. These findings
      implied that the pathogenesis of GS is a distention of the ligaments between the
      atlas and axis rather than loosening of the ligaments caused by the spread of an
      inflammatory edema from the soft tissues of the neck as has been proposed by
      others.

PMID- 9195152
TI  - Ultrastructural findings of the macula utriculi in a case of a petrous apex
      cholesteatoma: a comparison with findings in a patient with an acoustic neuroma.
AB  - The morphological characteristics of the vestibular sensory cells of the macula
      utriculi obtained during surgery in a patient with a petrous apex cholesteatoma
      were examined using scanning and transmission electron microscopy. Findings were
      compared to cells studied in a patient with acoustic neuroma. Scanning electron
      microscopy showed that compared to the apparently normal cells in the acoustic
      neuroma case, most sensory cells in the cholesteatoma case had large cuticular
      plates, irregular locations of cilia and no clear polarizations. Supporting cells
      showed profuse short microvilli on the whole surface. With transmission electron
      photomicrographs, type I hair cells were not seen and certain morphological
      changes were observed in type-II-like cells and supporting cells. We presume that
      the degenerative changes in the vestibular epithelia were due to circulatory
      disturbances and/or direct pressure applied to the vestibular nerve at the
      internal auditory canal, with subsequent involvement of the macula utriculi.

PMID- 9195153
TI  - Chondrosarcoma of the nasal septum.

PMID- 9195155
TI  - Relationship estimation in affected sib pair analysis of late-onset diseases.
AB  - In linkage studies, errors in pedigree structure will often be uncovered through
      Mendelian inconsistencies. In affected sib pair analysis of diseases with late
      onset, however, such mistakes will usually go undetected since parental genotypes
      are commonly not known. Cases of nonpaternity, unrecorded adoption or accidental
      sample swap in the laboratory will then not be noticed. Typically, such
      relationship errors lead to a decrease in power for linkage. In this paper, a
      method is presented which allows verification of the relationship between stated
      sibs using their marker genotypes. The method is likelihood-based and
      incorporates a Bayesian approach to compute posterior relationship probabilities.
      It is shown that sibs, half-sibs and unrelated individuals can be distinguished
      from each other quite reliably using numbers of markers that should be available
      in most sib pair studies. It is demonstrated that elimination of false sib pairs
      increases the power to detect linkage in affected sib pair studies. The gain in
      power may be large if relationship errors occur quite frequently; the gain will
      be only moderate if relationship errors are very infrequent. Software for
      relationship estimation is provided.

PMID- 9195154
TI  - Characterisation of X;17(q12;p13) translocation breakpoints in a female patient
      with hypomelanosis of Ito and choroid plexus papilloma.
AB  - An X;17 translocation breakpoint was characterised in a 5-year-old female with
      hypomelanosis of Ito (HI) who exhibits characteristic hypopigmented lesions,
      psychomotor retardation, and choroid plexus papilloma. A YAC clone containing the
      locus DXS1 from Xq12 was found by fluorescence in situ hybridisation to cross the
      translocation breakpoint. Cosmid clones positive for DXS1 were used to identify
      and clone the translocation junction fragment from the patient's DNA. A
      chromosome-17-specific DNA fragment was isolated and used to identify cosmid
      clones crossing the translocation from chromosome 17p13. Exon trapping identified
      two known genes from chromosome 17: FMR1L2 (the fragile X mental retardation
      syndrome like protein 2) and SHBG (human sex hormone-binding globulin). Mapping
      the FMR1L2 and SHBG genes showed that neither gene was disrupted by the
      translocation.

PMID- 9195156
TI  - The meiotic segregation pattern of a reciprocal translocation
      t(10;12)(q26.1;p13.3) by fluorescence in situ hybridization sperm analysis.
AB  - The meiotic segregation of chromosomes 10 and 12 was analyzed in a male
      heterozygous for a reciprocal translocation, t(10;12)(q26.1;p13.3), using
      fluorescence in situ hybridization (FISH). Centromeric specific probes that
      detect alpha satellite sequences of chromosomes 10 and 12 were used. A total of
      10,049 spermatozoa were analyzed. The frequencies of alternate/adjacent 1,
      adjacent 2, and 3:1 modes of segregation were: 84.25, 10.95%, and 4.42%,
      respectively. Diploidy was present in 0.23% of spermatozoa. Similar segregation
      patterns have been reported for this donor by direct karyotyping of sperm cells.
      FISH is a valuable technique for studying meiotic segregation patterns in that
      larger samples can be studied in a relatively short time. However, it does not
      provide information on the full chromosome complement of the spermatozoon.

PMID- 9195157
TI  - Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in
      Mediterranean families.
AB  - Recent studies show a susceptibility locus (DFNB1) responsible for non-syndromic
      neurosensory autosomal-recessive deafness (NSRD) mapping to the pericentromeric
      region of chromosome 13q. In order to better understand the frequency with which
      DFNB1 is the gene for deafness in our patient population and the role of DFNB1 in
      Caucasians, we performed a genetic linkage study with four microsatellite markers
      linked to DFNB1 in a total of 48 independent Mediterranean families, of which 30
      and 18 were of Italian and Spanish descent, respectively. A maximum two-point lod
      score of 7.28 was found with marker D13S115 at a recombination frequency of theta
      0.1. Significant lod scores were also obtained for D13S143, D13S292 and D13S175.
      Genetic heterogeneity was confirmed using the HOMOG program which indicated
      absence of linkage to DFNB1 in approximately 21% of the sample. This study
      clearly demonstrates that DFNB1 plays an important role in 79% of Mediterranean
      families with NSRD. Furthermore, results from multipoint analysis predict that
      the DFNB1 gene maps between markers D13S175 and D13S115 which are separated by
      approximately 14.2 cM.

PMID- 9195158
TI  - The fragile X CGG repeat shows a marked level of instability in hereditary non
      polyposis colorectal cancer patients.
AB  - The allelic variation of the FMR1 CGG repeat was investigated by small-pool PCR
      in nonneoplastic peripheral blood leukocytes from HNPCC patients and matched
      controls for similar CGG repeat lengths. The allelic variation for repeat lengths
      appears to be roughly twice as frequent in HNPCC patients as in controls,
      especially when patients are mutated in hMLH1. There are more expansions in HNPCC
      patients (42%) than in controls (20%) but this difference is statistically
      borderline. The mean length of expansions relative to the genuine size did not
      differ in HNPCC patients or controls (respectively 17% and 20% of the
      constitutional allelic length). The reported data suggest that instability within
      nonneoplastic cells of a subset of HNPCC patients might be one mechanism for
      transition from normal to the premutation range of the FMR1 CGG repeat.

PMID- 9195159
TI  - A single-tube PCR test for the diagnosis of Angelman and Prader-Willi syndrome
      based on allelic methylation differences at the SNRPN locus.
AB  - The analysis of allelic methylation differences in 15q11-q13 has been established
      as a valid test for the Angelman and Prader-Willi syndromes. Current tests use
      methylation-sensitive restriction enzymes and Southern blot analysis. Here we
      describe a single-tube PCR test. It is based on sodium bisulfite treatment of
      DNA, which converts unmethylated, but not methylated cytosine residues to uracil,
      and PCR primers specific for the maternal and the paternal allele. The method was
      validated in a blinded retrospective study on 87 DNA samples from normal controls
      and patients. Prospective studies by independent laboratories will be needed
      before this assay can replace Southern blot analysis in routine diagnostic
      procedures.

PMID- 9195160
TI  - Chromosomal localization of the adrenoleukodystrophy-related gene in man and
      mice.
AB  - We report here on the chromosomal mapping of the adrenoleukodystrophy-related
      (ALDR) gene on both the human and the mouse genomes. This gene encodes a
      peroxisomal ATP binding cassette transporter, closely related to the transporter
      identified as responsible for the adrenoleukodystrophy phenotype. ALDR maps on
      the syntenic region on murine and human autosomes. In addition, we could
      determine its position in relation to known microsatellite framework markers;
      this will allow to test its role in Zellweger syndrome and/ or related
      peroxisomal disorders.

PMID- 9195161
TI  - Mapping of the tyrosine kinase receptors trkA (NTRK1), trkB (NTRK2) and
      trkC(NTRK3) to human chromosomes 1q22, 9q22 and 15q25 by fluorescence in situ
      hybridization.
AB  - trk (NTRK) genes encode tyrosine kinase transmembrane receptors that are
      stimulated by neurotrophins, and are responsible for the transduction of signals
      controlling neuropoiesis and neuron survival in the central and peripheral
      nervous system, trkA gene has earlier been assigned to three different loci on
      chromosome 1. To resolve these conflicting results, and confirm the localization
      of trkB and trkC, probes specific to each of these related genes were constructed
      and used in fluorescent in situ hybridization on human metaphase cells. Our
      results indicate that trkA, trkB and trkC are located in chromosome bands 1q22,
      9q22 and 15q25, respectively.

PMID- 9195162
TI  - Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female
      with mild mental retardation.
AB  - Balanced chromosomal abnormalities such as translocations and inversions have
      been identified in many genetic diseases. Cloning of the breakpoints involved in
      these abnormalities has led to the identification of the disease-related genes.
      Recent reports suggest the presence of a mental retardation locus at Xq11-12. We
      have identified a female patient with a balanced translocation t (X;12) (q11;q15)
      associated with mild mental retardation. We identified a yeast artificial
      chromosome spanning the X-chromosome breakpoint by using fluorescent in situ
      hybridization techniques. A cosmid library of this YAC has been constructed and
      the search for candidate genes is in progress.

PMID- 9195164
TI  - Measuring surgical performance in acute abdominal pain: some reflections from
      international studies.

PMID- 9195163
TI  - Assignment and ordering of twenty-three unique NotI-linking clones containing
      expressed genes including the guanosine 5'-monophosphate synthetase gene to human
      chromosome 3.
AB  - Twenty-three unique NotI-linking clones, mainly isolated from the NRL1 library,
      were mapped and ordered by fluorescence in situ hybridization to human chromosome
      3. All these clones were partially sequenced around the NotI sites and thus
      represent sequence-tagged sites. The EMBL nucleotide database was then searched
      with sequences from the NotI-linking clones using the FASTA program. This search
      revealed that the NRL-090 clone (at 3q24) contains the gene encoding human
      guanosine 5'-monophosphate synthetase (GMPS-PEN). To our knowledge, this is the
      first localization of this gene. Clone NL1-320 (at 3p21.3) contains a gene
      encoding arginine tRNA (97.3% identity in 73 bp), while clones NRL-063, NRL-097
      and NRL-143 contain expressed sequences with unknown functions. Other clones
      displayed 60-85% similarities to cDNAs, CpG islands and other genes.

PMID- 9195165
TI  - Allelic loss on chromosome 11 is uncommon in parathyroid glands of patients with
      hypercalcaemic secondary hyperparathyroidism.
AB  - OBJECTIVE: To test the hypothesis that progression of secondary
      hyperparathyroidism from normocalcaemia to hypercalcaemia occurs because of
      development of monoclonal parathyroid tumours after the inactivation of a tumour
      suppressor gene on chromosome 11q13. DESIGN: Experimental study. SETTING:
      University hospital, Sweden. SUBJECTS: 13 Patients with secondary hypercalcaemic
      hyperparathyroidism. INTERVENTIONS: 48 Parathyroid glands were removed, 39 of
      which were analysed using Southern blot hybridisation and polymerase chain
      reaction. MAIN OUTCOME MEASURES: Loss of heterozygosity on several loci on
      chromosome 11, including 11q13, which carries the presumed gene for multiple
      endocrine neoplasia type 1 (MEN1). RESULTS: Monosomy for chromosome 11 was found
      in one tumour. CONCLUSIONS: It seems unlikely that the MEN1 gene is of importance
      in the progression of secondary hyperparathyroidism.

PMID- 9195166
TI  - Direct carbon dioxide insufflation of the retroperitoneum under laparoscopic
      control for renal and adrenal surgery.
AB  - OBJECTIVE: Assessment of the videoscopic approach to the retroperitoneal space in
      the vicinity of the kidney and the adrenal gland. DESIGN: Open study. SETTING:
      University hospital, Belgium. SUBJECTS: 10 patients who underwent 11 operations
      (adrenalectomy, n = 3, nephrectomy, n = 5, partial nephrectomy, n = 2, and renal
      cystectomy, n = 1). INTERVENTIONS: Direct CO2 insufflation of the retroperitoneal
      space in order to obtain a convenient retroperitoneal working space for renal and
      adrenal surgery. OUTCOME MEASURES: Feasibility, morbidity and mortality. RESULTS:
      8 patients were operated on exclusively by the retroperitoneoscopic approach; 2
      required the retroperitoneal and transperitoneal routes to be combined to
      complete an adrenalectomy. No patients required blood transfusion and no patient
      died. Median postoperative stay was 3 days. CONCLUSION: The CO2 insufflation
      technique of the retroperitoneum is safe and reproducible. Nevertheless, far from
      excluding each other, both approaches-laparoscopic and retroperitoneoscopic-are
      complementary in difficult cases, particularly for adrenal endoscopic surgery and
      for larger renal lesions.

PMID- 9195167
TI  - Leakage of intrathoracic oesophagovisceral anastomoses in adenocarcinoma of the
      gastric cardia: changes in serial APACHE II scores and their prognostic
      significance.
AB  - OBJECTIVE: To evaluate changes in serial Acute Physiology and Chronic Health
      Evaluation (APACHE) II scores in patients with intrathoracic oesophageal
      anastomotic leaks and to assess their prognostic significance. DESIGN:
      Retrospective study. SETTING: Teaching hospital, Taiwan. SUBJECTS: 18 patients
      (4%) who developed intrathoracic oesophageal anastomotic leaks in a total of 491
      patients who underwent oesophagogastrectomy for adenocarcinoma of the gastric
      cardia between 1980 and 1994. MAIN OUTCOME MEASURE: APACHE II scores in those
      that survived (n = 10) compared with those who died (n = 8). RESULTS: Of the 18
      patients, 8 (44%) died. The preoperative general condition, biochemical data, and
      perioperative APACHE II scores were similar in the two groups. Leakage from the
      oesophageal anastomoses caused similar degrees of sepsis in the two groups in
      terms of APACHE II scoring, but the APACHE II scores of survivors started to
      decline within a week of initial management. In contrast, the APACHE II scores of
      those who died had increased one week after the leak had been diagnosed despite
      initial management. There were significant differences in the APACHE II scores of
      survivors and those who died from one week after leakage until discharge or death
      (p < 0.001). Only one patient (1/9) survived if the APACHE II score one week
      after diagnosis of the leak was more than 10. None died of the leak if the APACHE
      II scores were equal to or less than 10 after a week. CONCLUSIONS: Adequate
      surgical drainage, antibiotic cover according to the microbiological picture, and
      nutritional support are essential in the management of intrathoracic oesophageal
      fistulas. Early reoperation to close early leaks by simple suture or secondary
      wrapping and to improve local drainage is recommended. The APACHE II scoring
      system is valuable in evaluating the severity of sepsis caused by intrathoracic
      oesophagovisceral anastomosis leaks and may serve as an indicator of adequate
      management. Aggressive surgical measures should be considered if APACHE II scores
      rise during initial management.

PMID- 9195168
TI  - Complications of percutaneous endoscopic gastrostomy.
AB  - OBJECTIVE: To report our experience of percutaneous endoscopic gastrostomy with
      particular reference to complications and tube dysfunction. DESIGN: Retrospective
      study. SETTING: Teaching hospital, Denmark. SUBJECTS: 135 patients who required
      178 gastrostomy tubes between 1.1.1990 and 30.6.1994. INTERVENTION: 101 patients
      had the tubes inserted by the introducer technique and 34 by the pull-through
      method. MAIN OUTCOME MEASURES: Complications and incidence of tube dysfunction.
      RESULTS: The overall complication rate was 43/135 (32%), including tube
      dysfunction; 17 (13%) developed a serious complication (intraperitoneal leakage,
      wound infection, or subcutaneous emphysema) and 6 died (4%). In each case the
      introducer had been used. 28 patients (21%) had a non-functioning tube exchanged
      sometimes more than once. The mean life-span of the tubes were 3.8 months, and
      seemed to be independent of the technique chosen for introduction. 66 patients
      (49%) died with a functioning tube. 24 (18%) died within a month of the
      insertion. CONCLUSION: serious complications leading to laparotomy, wound
      infection, or intraperitoneal abscess developed in 17 patients (13%), in all of
      whom the introducer technique had been used. The safer pull-through technique is
      therefore recommended.

PMID- 9195169
TI  - Prospective evaluation of a treatment protocol in patients with severe acute
      necrotising pancreatitis.
AB  - OBJECTIVE: Audit of the protocol for surgical treatment of patients with acute
      severe and necrotising pancreatitis (ANP). DESIGN: Prospective open study.
      SETTINGS: University hospital, Finland. PATIENTS: 33 patients treated for severe
      (Ranson score 3 or more) and necrotising (as judged on computed tomograms (CT))
      pancreatitis between 1992-1993. PROTOCOL: Indications for antibiotic treatment (n
      = 25 patients) were: fulminant multiorgan disease; recurrent continual parallel
      increase in temperature, white cell count (WCC) and C-reactive protein
      concentration; or the presence of bacteria on Gram stain of a percutaneous fine
      needle aspiration smear of necrosis. Three of the 25 responded to antibiotics.
      They and eight others with ANP but without these indications were treated
      conservatively. Twenty-two patients underwent repeated necrosectomy by
      laparostomy. MAIN OUTCOME MEASURES: Diagnosis of pancreatic infection, morbidity
      and mortality RESULTS: Of the 22 patients operated on 17 had contaminated
      necrosis at operation, and this had been predicted by the increasing inflammatory
      variable and the presence of bacteria in the Gram stain. Five patients operated
      on died (23%), four of the five having been operated on for fulminant multiorgan
      disease (80%). Recurrent sepsis developed in five patients, pancreatic fistulas
      in two, and there were no pseudocysts. Gastrointestinal fistulas developed in 12
      patients, but not after we had changed the technique of wound packing. All 11
      patients treated conservatively survived. CONCLUSION: A third of patients with
      ANP can be selected for safe non-operative treatment. Infected ANP can be treated
      by repeated necrosectomy by laparostomy with low mortality (6%). Early fulminant
      multiorgan disease should not be treated with laparostomy.

PMID- 9195170
TI  - Reappraisal of pancreaticojejunostomy after pancreaticoduodenectomy: a report of
      86 cases with particular reference to the rate of pancreatic fistulation.
AB  - OBJECTIVE: To report our experience of 86 patients who underwent
      pancreaticoduodenectomy followed by pancreaticojejunostomy, paying particular
      attention to the rate of fistulation. DESIGN: Retrospective study. SETTING: Two
      teaching hospitals, France. SUBJECTS: 86 patients (58 men and 28 women) who
      required pancreatic resection for adenocarcinomas of the head of the pancreas (n
      = 34), chronic pancreatitis (n = 21), cancer of the ampulla of Vater (n = 12),
      cancer of the distal bile duct (n = 6), or other causes (n = 13). INTERVENTION:
      Pancreaticoduodenectomy followed by pancreaticojejunostomy with mucosa to mucosa
      suture. RESULTS: 26 patients (30%) developed complications, 9 (10%) required
      reoperation, and 8 (9%) died postoperatively. Pancreatic fistulas developed in 2
      (2%), one of whom was successfully treated conservatively. The other was
      reoperated on and died on day 40. CONCLUSION: Pancreaticojejunostomy after
      pancreaticoduodenectomy is safe, and the rate of fistulation compares favourably
      with that after pancreaticogastrostomy (2%).

PMID- 9195171
TI  - Preoperative local infiltration with ropivacaine for postoperative pain relief
      after inguinal hernia repair. A randomised controlled trial.
AB  - OBJECTIVE: To assess the effect of preoperative local anaesthesia with
      ropivacaine and find out if there was a dose-response relationship with
      postoperative pain after inguinal hernia repair. DESIGN: Randomised, double
      blind, placebo-controlled trial. SETTING: Two Swedish and two Norwegian
      hospitals. SUBJECTS: 131 Male patients undergoing elective inguinal hernia
      repair. INTERVENTION: Infiltration of the inguinal field before operation with
      0.5% ropivacaine 40 ml (200 mg), 0.25% ropivacaine 40 ml (100 mg) or saline 40
      ml. MAIN OUTCOME MEASURES: Wound pain at rest and during mobilisation, pressure
      exerted to reach pain threshold and maximum pain tolerance after 3, 6, 10, and 24
      hours, and after 7 days; consumption of analgesics; and Quality of Life assessed
      by two independent questionnaires before and after operation. RESULTS: Pain
      scores after 3 hours were significantly lower in the ropivacaine groups compared
      with the saline group for all variables (p < 0.05). At 6 hours pain scores were
      significantly lower for ropivacaine 0.5% compared with saline for wound pain
      during mobilisation and pressure exerted to reach maximum pain tolerance.
      Patients given saline made their first request for analgesics significantly
      sooner than in the other two groups (p < 0.05), and a significantly larger
      percentage of them requested analgesics during the first 24 hours (p < 0.05).
      Evaluation of the Quality of Life questionnaires showed no significant
      differences between the groups. CONCLUSION: Ropivacaine has a significant, dose
      related pain-reducing effect in the immediate postoperative period but we could
      find no support for the theory that preoperative infiltration analgesia reduces
      long term pain.

PMID- 9195172
TI  - Correlations between endotoxin, interferon-gamma, biopterin and serum
      phospholipase A2-activities during lethal gram negative sepsis in rats.
AB  - OBJECTIVE: To establish a standardised reproducible animal model of
      intraperitoneal sepsis, and to investigate early immunoserological responses to
      find a mediator-based system for evaluation and grading of diffuse peritonitis in
      patients DESIGN: Prospective experimental study SETTING: 4 Teaching hospitals,
      Germany and Austria MATERIAL: 42 LEW. 1W rats, 12 of which acted as controls
      INTERVENTIONS: Gram negative sepsis was induced by intraperitoneal injection of 6
      ml of a mixture of Escherichia coli (K1:H+) 10(10) organisms/ml, autogenous
      haemoglobin 2.9 ml (haemoglobin concentration 3%), 0.9% sodium chloride 3 ml, and
      suspension 0.1 ml. Control rats were given physiological saline 6 ml alone. MAIN
      OUTCOME MEASURES: Concentrations of endotoxin, interferon gamma (IFN-gamma), and
      biopterin, and serum phospholipase A2 (PLA2) activity. RESULTS: There were
      significant differences between the septic and control rats in concentrations of
      endotoxin (EU/ml) (median (interquartile range) 21.85 (2.02-159.5) compared with
      0, p < 0.0001; IFN-gamma (pg/ml) 1263.0 (271.0-7575.0) compared with 101.0 (89.0
      141.0), p < 0.0001; biopterin (nmol/L) 111.0 (66.4-156.3) compared with 53.7
      (38.3-67.6), p < 0.001; and PLA2 (U/L) 163.0 (125.8-209.0) compared with 112.5
      (88.5-126.5) p < 0.01. CONCLUSIONS: Measurements of concentrations of endotoxin,
      IFN-gamma, pteridines, and PLA2 activity may well be adequate markers for early
      recognition of sepsis, and perhaps for grading it during the first 6 hours after
      induction. The allow a clear distinction to be made between septic and non-septic
      disorders in 87% of cases.

PMID- 9195173
TI  - Neurotensin increases intestinal adaptation and reduces enteroglucagon-like
      immunoreactivity after large bowel resection in rats.
AB  - OBJECTIVE: To assess the effects of giving neurotensin on intestinal adaptation
      after colectomy and their relation to enteroglucagon-like immunoreactivity.
      DESIGN: Laboratory experiment. SETTING: Teaching hospital, Spain. MATERIAL: 55
      Male Wistar rats. INTERVENTIONS: All animals were anaesthetised before undergoing
      laparotomy; 24 animals had 75% of their colon resected. Half of the animals (12
      in each group) were treated with neurotensin (600 micrograms/kg body wt/day) for
      14 days. MAIN OUTCOME MEASURES: Differences in the number of mitoses and in
      nuclear antigen staining of proliferating cells in the intestinal mucosal crypts;
      plasma enteroglucagon-like immunoreactivity. RESULTS: After colon resection, the
      proliferative status, number of mitoses (p < 0.01), and nuclear antigen staining
      of proliferating cells (p < 0.001) increased significantly in the jejunum of
      animals treated with neurotensin (p < 0.05). Less pronounced effects were
      observed in colon and ileum. Plasma enteroglucagon-like immunoreactivity levels
      fell significantly in all animals given neurotensin (p < 0.05). CONCLUSIONS:
      Neurotensin increases the adaptive intestinal process after colon resection and
      reduces plasma enteroglucagon-like immunoreactivity in rats.

PMID- 9195174
TI  - Laparoscopic resection of a giant mesenteric cystic lymphangioma.

PMID- 9195175
TI  - Mechanisms of adhesion development and effects on wound healing.
AB  - This paper reviews the evidence that glove powder plays an important role in
      adhesion formation and has adverse effects on the healing of abdominal incisional
      wounds. The underlying mechanisms leading to these adverse effects are beginning
      to be revealed. By affecting the mesothelial cell function, powder contamination
      disrupts the delicate balance of fibrin deposition and degradation, provoking
      adhesion formation, and interfering with wound healing. Studies are described
      showing that starch impairs incisional wound healing by its effect on the T cell
      mediated immune system. Furthermore starch powder may act as a vector for
      endotoxin. This paper concludes that starch powder is harmful and its use in a
      hospital setting can no longer be supported.

PMID- 9195176
TI  - Misdiagnosis of cancer due to multiple glove powder granulomas.
AB  - A biologically absorbable powder, the cornstarch lubricant used in the production
      of gloves, is treated with epichlorohydrin, a cross-linking agent forming one to
      three diether glycerine groups to create a glove lubricating powder. This agent,
      together with chemicals used in glove fabrication is able to interfere with
      important biological diagnostic procedures, such as polymerase chain reaction
      (PCR) and enzyme immunoassay as well as to induce a granulomatous reaction in
      traumatised surgical tissue.

PMID- 9195177
TI  - Post-operative peritoneal adhesions and foreign bodies.
AB  - One of the proven causes of adhesions is foreign microbodies which are present in
      up to 93% of all re-operated patients in which adhesions are analysed for
      evidence of external contamination. Studies are described which show the changing
      nature of foreign microbodies with time, associated with the development of new
      surgical practices. This paper concludes that although foreign bodies found today
      may not be the same as those found 30 years ago, they remain prominent in the
      aetiology of adhesions--the main cause of postoperative intestinal obstruction.
      Every effort should be made to minimise tissue contamination during operations
      with particulate debris such as glove powder.

PMID- 9195178
TI  - Type I allergies to latex and the aeroallergenic problem.
AB  - Between 1989 and 1995, a 12-fold increase in latex allergy was documented amongst
      our patients. Similar findings have been noted elsewhere. Increase in type I
      allergies to latex has become an international problem. The issues associated
      with latex allergy are described, including those posed by the ubiquitous nature
      of latex in medical equipment, and in commonplace domestic objects. The potential
      for allergic patients to cross react to a variety of fruits or plants is an added
      problem for sensitized patients. This paper concludes that the universal
      introduction of powder-free surgical gloves with low protein content would be a
      very important measure in the prevention of acquired latex allergy.

PMID- 9195179
TI  - Glove powder--a risk factor for the development of latex allergy?
AB  - Studies are described which compare the prevalence of sensitisation against latex
      proteins in medical personnel in different hospitals. The objective of these
      studies was to find out whether the use of powdered or unpowdered gloves could be
      related to the prevalence of latex allergy. Employees of one of the investigated
      hospitals (Germany) were using only powdered latex gloves, and in the other two
      hospitals (Great Britain) low protein powder-free latex gloves were used. Methods
      by which latex allergy can be avoided are suggested.

PMID- 9195180
TI  - Setting standards for product selection: allergy prevention.
AB  - It is axiomatic to state that if products made of natural rubber latex were not
      used in health care settings then there would be no problems of acquired
      hypersensitivity from such products. Although synthetic materials are available
      they do not currently possess the same technical qualities of elasticity and
      comfort, nor do they deliver the desired degree of protection against biological
      agents as gloves made out of natural rubber latex. Selection of gloves either for
      non-sterile procedures or sterile surgical use should be based on this
      understanding, and gloves with minimal levels of extractable latex proteins
      should be used.

PMID- 9195181
TI  - Airborne particles from latex gloves in the hospital environment.
AB  - Air sampling studies are described which show high levels of airborne starch
      powder contamination in areas where powdered latex gloves are used. Furthermore,
      culture of collected samples show a clear association between starch particles
      and bacterial colonies in an experimental system suggesting that airborne
      particles could act as a vector for pathogens in the hospital environment.

PMID- 9195182
TI  - Effects of powder on infection risks and associated mechanisms.
AB  - This paper examines the release of Tumour necrosis factor alpha, (TNFa)
      interleukin 1, eicosanoids, and hydrogen peroxide from macrophages exposed to
      glove starch particles. Studies are described which show that T-cell responses
      are potently activated by glove powder products leading to the release and
      formation of high amounts of pro-inflammatory mediators, ultimately resulting in
      adverse clinical consequences such as starch peritonitis or adhesions.

PMID- 9195183
TI  - Powder contamination of extradural catheters and implications for infection risk.
AB  - Previous papers in this supplement have addressed contamination of the peritoneal
      cavity by powder from the surgeon's gloves, or via airborne starch particles.
      This paper examines the possibility that medical devices placed inside patients
      may also become contaminated with powder from gloves during handling and
      insertion. In this way, glove powder may subsequently find its way into body
      cavities.

PMID- 9195184
TI  - Cost implications of adhesions as highlighted in a European study.
AB  - For a hospital, the medical costs of dealing with post-operative adhesions can be
      very high. Studies to determine the extent of these costs are described, together
      with a suggested strategy by which surgeons may help avoid future cases of
      adhesion formation.

PMID- 9195185
TI  - Cost implications of allergy and recent Canadian research findings.
AB  - The cost to hospital's managing latex allergy problems, and of instituting a co
      operative response to the problem is estimated, and compared with the estimated
      cost of ignoring the problem. The costs and benefits of the interventional
      strategies, i.e. complete elimination of powdered latex gloves in favour of
      powder free latex gloves, are described in detail. It is demonstrated that the
      chosen interventional strategy not only reduced overall costs, but surprisingly,
      also reduced glove purchase costs.

PMID- 9195186
TI  - Cost of latex device-related occupational illness, workmen's compensation and
      legal issues.
AB  - In the United States, health care workers who become sensitised to latex face
      substantial problems. Their careers may prematurely come to an end, leaving them
      with a long struggle to achieve adequate compensation. This paper outlines some
      of those problems, and the actions necessary by employers, employees and worker
      disability groups to prevent future problems.

PMID- 9195187
TI  - Scientific career and main scientific achievements of Professor Katalin S.-Rozsa,
      Dr. Sci.

PMID- 9195189
TI  - The molting gland of the cockroach Periplaneta americana: secretory activity and
      its regulation.
AB  - 1. The prothoracic gland is the main source of ecdysteroids in larvae of the
      cockroach Periplaneta americana. 2. Besides ecdysone the molting gland of
      Periplaneta secretes 3-dehydroecdysone and proteins. 3. The molting gland of
      Periplaneta is regulated in different successive steps of cooperation of nervous
      and neuroendocrine activity. 4. Neurogenic effects on the molting gland via the
      prothoracic gland nerves are concentrated on the period of prepeak production of
      ecdysteroids. 5. Prior to the 17th day, the glands secretory activity is
      inhibited by GABA-ergic neuronal pathways from the subesophageal ganglion. 6.
      Neurogenic disinhibition by a peptidergic brain factor elicits the competence of
      the gland for prepeak activity, completed by the glandotropic effect of PTTH. 7.
      The 17th day of the larval stage is characterized as the head critical period,
      i.e., after this period the ecdysteroid secretion of the gland is independent of
      the prothoracicotropic hormone (PTTH) from the brain. 8. The main peak of
      ecdysteroid production is regulated by prothoracicotropic neuropeptids from the
      brain.

PMID- 9195188
TI  - In vivo neuropharmacological and in vitro laser ablation techniques as tools in
      the analysis of neuronal circuits underlying behavior in a molluscan model
      system.
AB  - 1. This paper reviews the selective lesioning techniques employed to elucidate
      the role of the neurotransmitters dopamine and serotonin and single, identified
      interneurons in the feeding system of the pond snail Lymnaea stagnalis. 2. The
      pathway lesioning work reviewed in this paper showed that dopamine is necessary
      for the feeding response to occur and serotonin has a mainly modulatory role in
      the feeding system of Lymnaea. 3. The photoinactivation results reviewed here
      assist in the elucidation of the different roles that different types of
      interneurons play in the initiation and modulation of patterned neuronal activity
      underlying feeding.

PMID- 9195190
TI  - Control of circulation in insects.
AB  - 1. Studies on the physiology of insect circulation have revealed that the insect
      central nervous system can exert a strong nervous control over certain dorsal
      vessels and diaphragms. 2. The function of neurohormonal control over the
      heartbeat of insects, though demonstrated, is less clear. In contrast with
      studies on the central nervous and skeletal neuromuscular systems, not one
      neurotransmitter substance has been identified in any of the vessels, pumps or
      diaphragms responsible for circulation in insects. 3. A coelopulse system was
      identified and described that suggested a very sophisticated coordination between
      circulation and respiration in insects. The circulatory systems of cockroach,
      locust, fly, moth and bee all involve unique specializations. 4. It is suggested
      that an autonomic nervous system is present in insects and is responsible for
      coordination and control of both circulation and respiration.

PMID- 9195191
TI  - Opiate signaling regulates microglia activities in the invertebrate nervous
      system.
AB  - 1. Evidence supporting the presence in the invertebrate nervous system of a class
      of glial cells resembling vertebrate microglia was obtained in the freshwater
      snail Planorbarius corneus. These cells are easily identified by their
      immunopositivity to anti-pro-opiomelanocortin (POMC)-derived peptide antibodies.
      2. Invertebrate microglia, as in vertebrates, exhibit macrophage-like activity in
      vivo and in cell cultures. These cells respond to the trauma of ganglionic
      excision and their organotypic culture by leaving their location around neurons
      and moving to the lesion site from which they migrate in the culture dish. 3. In
      vitro, these microglia undergo conformational changes and show phagocytic
      properties in the presence of bacteria or lipopolysaccharide. The activated cells
      also express tumor necrosis factor-alpha-like material and an increase in nitric
      oxide synthase, as shown by immunocytochemistry. 4. The inhibitory effect of
      morphine on the mobility and phagocytic activity of invertebrate microglia
      provide additional functional evidence for a possible role of opiate-like
      compounds in downregulating immunoregulatory processes, as also observed in the
      circulating immunocytes.

PMID- 9195192
TI  - Nicotinic antagonists (piperidines and quinuclidines) reduce the susceptibility
      of early sea urchin embryos to agents evoking calcium shock.
AB  - 1. Some nicotinic antagonists (piperidine and quinuclidine derivatives and bis
      quaternary compounds) protect early embryos of the sea urchin Lytechinus pictus
      against a calcium shock evoked by ionomycin or a mixture of phorbol myristate
      acetate and nicotine. 2. Maximal protective potency was found for drugs that did
      not penetrate the plasma membrane. 3. Early sea urchin embryos have nicotinic
      acetylcholine receptors (nAChR) or nAChR-like structures localized on the cell
      surface that, apparently, take part in the control of Ca2+ influx.

PMID- 9195193
TI  - Quantitative distributions of different cholinesterases and inhibition of
      acetylcholinesterase by metidathion and paraquat in alimentary canal of common
      carp.
AB  - 1. The cholinesterases play an important role in the innervation of organs. The
      ratio of solubilized to membrane-bound cholinesterase and the quantitative
      distributions of acetylcholinesterase and butyrylcholinesterase were measured in
      different segments of the gut of carp (Cyprinus carpio) connected with different
      types of nerve-muscle synapses in different parts of the alimentary tract. 2. The
      inhibition of acetylcholinesterase (EC 3.1.1.7.) by the herbicide paraquat and
      the insecticide metidathion was measured in different parts of the gut of carp.
      3. Metidathion and paraquat significantly decreased the activity of
      acetylcholinesterase in different segments of the alimentary tract of common
      carp, in a concentration-dependent manner.

PMID- 9195194
TI  - Neurohumoral control of ionic pumping in molluscan muscle: III. Cholinergic
      control of the response to low potassium levels.
AB  - 1. Isolated radular protractor muscles (RPM) of Busycon canaliculatum show a
      complex response to potassium-free solution. 2. While exposed to a bathing
      solution lacking K+, the RPM begins to respond with a hyperpolarizing phase.
      Within minutes, this gives way to a depolarizing phase (DP). After readmission of
      a bathing solution containing K+, there is an extra hyperpolarizing phase. 3.
      Acetylcholine over a range of concentrations from 10(-8)M to 10(-3)M
      progressively enhances the DP. 4. The action of acetylcholine is sodium
      dependent.

PMID- 9195195
TI  - Metabotropic GABA receptors regulate acetylcholine responses on snail neurons.
AB  - 1. The A type of acetylcholine response of Helix neurons is downmodulated by low
      concentrations of GABA that do not elicit any measurable change in membrane
      potential or conductance. 2. We find that these physiological actions are
      associated with an increase in both intracellular cyclic AMP levels and 45Ca2+
      influx. 3. The modulation of the acetylcholine response by GABA is blocked when
      the neurons are injected with EGTA to prevent a rise in intracellular Ca2+
      concentration or when tolbutamide, an inhibitor of protein kinase A, is applied.
      4. These results are consistent with the effects of GABA being mediated by a
      metabotropic GABA receptor that is activated at very low GABA concentrations and
      mediates modulation of the acetylcholine response via regulation of intracellular
      Ca2+ and cyclic AMP levels.

PMID- 9195196
TI  - Opposite effects of interleukin-2 and interleukin-4 on GABA-induced inward
      currents of dialysed Lymnaea neurons.
AB  - 1. The effects of interleukin-2 (rhIL-2) and interleukin-4 (rhIL-4) were
      investigated on gamma-aminobutyric acid (GABA)-induced inward currents on
      isolated, identified neurons of Lymnaea stagnalis L. (Mollusca, Gastropoda) by
      using a concentration clamp technique. 2. It was shown that the interleukins
      modified the GABA-induced inward current in an opposite direction: rhIL-2 (2-100
      U/ml) decreased the peak value of IGABA in a dose-dependent manner, whereas rhIL
      4 (0.2-100 U/ml), on the contrary, potentiated it. Both types of modulation were
      partially or fully reversible. 3. The reversal potential of IGABA was not shifted
      by these cytokines. 4. The time-to-peak value and inactivation time constant of
      the gamma-aminobutyric acid (GABA)-induced current was decreased by rhIL-4. The
      modulatory effect of rhIL-4 was eliminated after conjugation of this cytokine
      with its antibody. 5. It appears that cytokines could play a role in regulating
      the neural excitability through GABA-erg mechanisms.

PMID- 9195197
TI  - The effects of pesticides on monoaminergic system related to periodic activity of
      mussels (Anodonta cygnea L.).
AB  - 1. The effect of a herbicide (paraquat) and an insecticide (methidation) on the
      periodic activity of mussel in relation to serotonin and dopamine levels and
      their release and uptake in nervous system was investigated. 2. LC50 values of
      methidation in 24-, 48-, and 96-hr treatments, respectively, were 50% lower than
      those of paraquat. 3. Serotonin and dopamine levels decreased in all three
      ganglia by 20% on average upon 24- and 48-hr in vivo treatments with paraquat. In
      the 96-hr treatment, however, both monoamines showed a 20-40% increase. With
      methidation treatment, the level of monoamines tested did not change
      significantly. 4. After paraquat treatment, both the average lengths of resting
      periods and their total duration significantly increased. Parallel to this, the
      average length of active periods and their total duration dramatically decreased.
      Methidation increased the average length and total duration of resting periods
      during the first 2 days at the expense of active periods. On the fourth day,
      however, the effect reversed: average length and total duration of active periods
      increased of the expense of parameters characteristic of the resting state.

PMID- 9195198
TI  - The effects of piracetam and its novel peptide analogue GVS-111 on neuronal
      voltage-gated calcium and potassium channels.
AB  - 1. With the use of the two-microelectrode voltage-clamp method, three types of
      voltage-activated ionic currents were examined in isolated neurons of the snail
      Helix pomatia: high-threshold Ca2+ current (ICa), high-threshold Ca(2+)-dependent
      K+ current (IK(Ca)) and high-threshold K+ current independent of Ca2+ (IK(V)). 2.
      The effect of bath application of the nootropics piracetam and a novel piracetam
      peptide analog, ethyl ester of N-phenyl-acetyl-L-prolyl-glycine (GVS-111), on
      these three types of voltage-activated ionic currents was studied. 3. In more
      than half of the tested cells, ICa was resistant to both piracetam and GVS-111.
      In the rest of the cells, ICa decreased 19 +/- 7% with 2 mM of piracetam and 39
      +/- 14% with 2 microM of GVS-111. 4. IK(V) in almost all cells tested was
      resistant to piracetam at concentrations up to 2 mM. However, IK(V) in two-thirds
      of the cells was sensitive to GVS-111, being suppressed 49 +/- 18% with 1 microM
      GVS-111. 5. IK(Ca) appeared to be the most sensitive current of those studied to
      both piracetam and GVS-111. Piracetam at 1 mM and GVS-111 at 0.1 microM decreased
      the amplitude of IK(Ca) in most of the cells examined by 49 +/- 19% and 69 +/-
      24%, respectively. 6. The results suggest that piracetam and GVS-111 suppression
      of voltage-activated calcium and potassium currents of the neuronal membrane may
      regulate (both up and down) Ca2+ influx into neurons.

PMID- 9195199
TI  - Serotonin depletion after prolonged chlorpromazine treatment in a simpler model
      system.
AB  - 1. Prolonged exposure of the pond snail Lymnaea stagnalis to micromolar
      concentrations of chlorpromazine (CPZ) results in marked changes in the serotonin
      (5-HT) content of the central nervous system. 2. High-performance liquid
      chromatography with electrochemical detection indicates that levels of 5-HT, but
      not those of dihydroxyphenyl-alanine (DOPA), dopamine or norepinephrine, were
      significantly decreased (e.g., to less than 40% of normal after 30 days of
      exposure to 1 microM CPZ in the bathing water). 3. Glyoxylate-induced
      fluorescence was depressed to undetectable levels in central, serotonergic
      neurons. 4. Performance of 5-HT-dependent motor behaviors was impaired. 5. The
      present results, in accord with earlier studies on the effects of chronic
      exposure to haloperidol, suggest that previously overlooked mechanisms of
      monoamine downregulation may contribute to long-term effects of antipsychotic
      drugs.

PMID- 9195200
TI  - Effect of molluscan neuropeptide RAPYFVamide on identified Helix pomatia L.
      neurons.
AB  - 1. The effect of Mytilus inhibitory peptide-related peptide RAPYFVamide, isolated
      from Helix pomatia brain, was studied on 21 different identified Helix neurons.
      2. It was found that the neuropeptide hyperpolarized 11 of the 21 neurons
      studied, inducing a K-dependent current. Not all neurons responded by
      hyperpolarization to the peptide application, though, in all cases the voltage
      dependent outward K and inward Ca currents were depressed. 3. This may show that,
      in the peptide effect, more than one type of K conductance is involved. 4. It is
      proposed that RAPYFVamide may have a functional role in the modulation of the
      feeding behavior in H. pomatia.

PMID- 9195201
TI  - Isolation of bioactive compounds from Helix aspersa nerve tissue and the effect
      of pQPPLPRYamide on heart, esophagus and central neurons of H. aspersa and rectum
      of Anodonta woodiana.
AB  - 1. Both acetone and methanol extraction was used to isolate bioactive compounds
      from 1000 Helix aspersa brains. 2. Seven compounds were isolated of which four
      were identified as follows: Ha-1, 5-hydroxytryptamine; Ha-3, GSPYFVamide; Ha-4,
      pQPPLPRYamide; Ha-5, SGYLAFPRMamide. There was insufficient material to identify
      Ha-2, Ha-6 and Ha-7. 3. Ha-4, pQPPLPRYamide, was found to excite the heart of H.
      aspersa, relax the esophagus and both excite (mainly) and inhibit central
      neurons. In addition, this peptide contracted the rectum of Anodonta woodiana. 4.
      It is concluded that pQPPLPRYamide is an example of a new molluscan peptide
      family, designated as PRYamide.

PMID- 9195202
TI  - Effectiveness and limitations of the use of the gonadotropin-releasing hormone
      agonist leuprolide acetate in the diagnosis of delayed puberty in males.
AB  - In order to evaluate the effectiveness of the gonadotropin-releasing hormone
      agonist leuprolide acetate in distinguishing gonadotropin deficiency from delayed
      puberty, a single subcutaneous dose of 20 micrograms/kg of leuprolide acetate was
      administered at 07.00 h to 14 patients with constitutionally delayed puberty and
      to 8 gonadotropin-deficient subjects, and serum gonadotropin and testosterone
      levels were determined at baseline and 1,2,3,6,12, and 24 h thereafter. The
      increase in gonadotropin and testosterone levels was significant in patients with
      delayed puberty, so that the mean peak luteinizing hormone and to a lesser degree
      the mean peak testosterone levels clearly differentiated normally delayed from
      gonadotropin-deficient puberty. However, when the peak gonadotropin and
      testosterone concentrations were analyzed individually, there was a considerable
      overlap between the two groups of males, limiting the usefulness of this test.

PMID- 9195203
TI  - Effect of low-dose oral and intravenous dexamethasone administration on growth
      hormone secretion in children.
AB  - Acute dexamethasone administration (2 mg/m2 i.v. and 4 mg orally) increases
      growth hormone (GH) release in children. We evaluated the effect of a low
      intravenous dose (1 mg/m2) of dexamethasone on GH secretion in 8 short normal
      children and in 6 GH-deficient children. There was a significant GH increase at
      120, 150 and 180 min in short normal children (maximal value: 18.9 +/- 2.1
      micrograms/l; mean +/- EP), compared to placebo administration. In contrast, no
      significant GH elevation was seen in GH-deficient children (1.3 +/- 0.4
      micrograms/l). There was no difference in the GH response after intravenous
      dexamethasone and oral clonidine in these same 8 short normal children and 6 GH
      deficient children. Although no significant GH release was observed after
      dexamethasone or clonidine in GH deficiency, an increase in GH after GH-releasing
      hormone was seen (6.1 +/- 1.9 micrograms/l). There was a significant GH increase
      (18.5 +/- 3.3 micrograms/l) after low-dose (2-mg) oral dexamethasone
      administration in another 8 short normal children, which was similar to values
      after intravenous injection. No side effects were noted after intravenous or oral
      dexamethasone. In conclusion, low-dose intravenous or oral dexamethasone
      administration causes a marked GH release in short normal children, probably
      mediated by hypothalamic structures.

PMID- 9195204
TI  - Growth hormone stimulates production of interferon-gamma by human peripheral
      mononuclear cells.
AB  - There is substantial evidence for interactions between the immune and endocrine
      systems at different levels. In the present study we investigated whether human
      growth hormone (hGH) could stimulate proliferation of interferon-gamma-secreting
      cells (IFN-gamma-SC), and production of IFN-gamma. Human peripheral blood
      mononuclear cells (PBMC) taken from 15 normal subjects were incubated with
      varying doses (200,400,600 and 800 ng/ml) of recombinant hGH. Samples of cells
      were also incubated with PBS buffer (without hGH) to serve as controls. Effects
      of hGH were studied by enumerating IFN-gamma-SC and by measuring the
      concentration of IFN-gamma using an Immunospot assay and an enzyme-linked
      immunosorbent assay, respectively. The results showed that hGH significantly
      increased both the number of IFN-gamma-SC and the concentration of IFN-gamma in a
      dose-dependent manner. The maximum effects were obtained in the presence of (400
      ng/ml) hGH (15 +/- .5 IFN-gamma-SC/10(6) PBMC and 300 +/- 55 U/ml IFN-gamma)
      compared to controls (4 +/- 2 IFN-gamma-SC/10(6) PBMC and 50 +/- 10 U/ml IFN
      gamma). The results of the present study suggest that hGH might influence the
      immune system by stimulating the proliferation of IFN-gamma-SC and the production
      of IFN-gamma.

PMID- 9195205
TI  - Influence of gender on the correlation between plasma growth hormone profiles and
      urinary growth hormone excretion.
AB  - A lot of interest has been directed towards the measurement of urinary growth
      hormone (GH) excretion instead of plasma GH profiles or provocation tests. We
      investigated the factors influencing the relationship between 24- and 3-hour
      plasma GH profiles and urinary GH excretion in a cohort of 113 pediatric patients
      with growth disorders and healthy volunteers. Plasma and urinary GH were measured
      by polyclonal immunoassays differing in cross-reactivity with 20 kD GH (100
      versus 46%), but not with 22-kD, dimer, deamidated and pituitary GH. In the 24
      hour urine samples, only urinary GH excretion expressed as nanograms per 24 h
      correlated with plasma GH parameters, whereas the correlations for short-term
      samples were strongest if urinary GH excretion was expressed as nanograms per
      gram creatinine (r = 0.70-79, p < 0.00005-0.0001). In short-term samples urinary
      GH excretion depends on urinary volume and should thus be expressed in nanograms
      per gram creatinine, whereas 24-hour samples correlate best when urinary GH is
      expressed as nanograms per period. We found a significant sex difference (p <
      0.02) in the correlation between 24-hour plasma GH profiles and urinary GH
      excretion with strong correlations in the female group (r = 0.63-0.78, p <
      0.00005-0.0002) and a lack of correlation in the male group. The sex difference
      in the correlations between serum and urinary GH may reflect sex differences in
      GH profiles and metabolism, with urinary GH better reflecting the basal and
      slowly clearing portion of plasma GH than spontaneous GH peaks. The difference in
      cross-reactivities of molecular GH forms in polyclonal assays may have an impact
      on the correlation between plasma and urinary GH. Thus, the diagnostic value of
      urinary GH measurement as compared to serum GH profiles needs to be further
      evaluated.

PMID- 9195206
TI  - Abnormal metabolism of type-IV collagen in normotensive non-insulin-dependent
      diabetes mellitus patients.
AB  - The objective of this study was to investigate the serum level of the 7S domains
      of type-IV collagen [IVc(7S)] and its relations with microangiopathy in non
      insulin-dependent diabetes mellitus (NIDDM). This study comprised 73 patients
      with NIDDM that were consulted in our outpatient clinic. Among the 73 NIDDM
      patients, 43 with normal arterial pressure were selected to assess the
      relationship between serum levels of 7S collagen and microangiopathy. There was a
      significant relationship between the serum IVc(7S) levels and the presence of
      retinopathy and nephropathy. These findings suggest that an increased IVc (7S)
      concentration may reflect the abnormal collagen metabolism of the vascular
      basement membrane in NIDDM patients. Column chromatography of the NIDDM patients'
      sera revealed the heterogeneity of immunoreactive type-IV collagen (7S) and
      showed that these domains were composed mainly of degradation products of type-IV
      collagen. These data suggest that degradation of IVc is accelerated in the
      vascular basement membrane of NIDDM patients.

PMID- 9195207
TI  - DAX-1 gene mutations and deletions in Japanese patients with adrenal hypoplasia
      congenita and hypogonadotropic hypogonadism.
AB  - Abnormality of the DAX-1 gene accounts for many instances of congenital adrenal
      hypoplasia. In the present study, we performed molecular genetic analysis of DAX
      1 in 4 unrelated Japanese patients with adrenal hypoplasia congenita and
      hypogonadotropic hypogonadism. A double-point mutation for V126M and W171X was
      identified in 1 family and a complex de novo insertion-deletion mutation was
      identified in a second. The DAX-1 gene was entirely deleted in a 3rd patient as
      well as in a 4th with the additional feature of glycerol kinase deficiency.

PMID- 9195208
TI  - Plasma 3 alpha-androstanediol glucuronide in normal children and in congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency.
AB  - Monitoring therapy for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      is difficult, although plasma determinations of 17 alpha-hydroxyprogesterone
      (17OHP), delta 4-androstenedione (delta 4A) and testosterone are helpful. We have
      studied the usefulness of monitoring plasma 3 alpha-androstanediol glucuronide (3
      alpha-AG) in group of 24 CAH patients aged from birth to 18 years. For
      comparison, normal values for age and pubertal stage were determined in a control
      group of 115 girls and 118 boys. Mean plasma levels were higher during the first
      year of life, decreased to a nadir between 1 and 4 years, and increased steadily
      thereafter, there was also a significant increase with pubertal stage. In 24
      pairs of blood samples obtained at the time of venopuncture and 2 h after, 3
      alpha-AG levels did not change (p > 0.05) demonstrating that 3 alpha-AG levels
      were not affected by stress. In the patients with CAH, positive correlations
      between plasma 3 alpha-AG and delta 4A (females, r = 0.73; males, r = 0.98),
      17OHP (females, r = 0.58; males, r = 0.84) and testosterone (females, r = 0.83;
      males, r = 0.97) were observed. Concordance between 3 alpha-AG and delta 4A was
      observed in 90% of all samples, and in 91% between 3 alpha-AG and testosterone.
      Our study demonstrates that 3 alpha-AG is a valid marker of control and its
      determination appears to be a reliable tool to monitor CAH.

PMID- 9195209
TI  - A case of Robinow syndrome accompanied by partial growth hormone insufficiency
      treated with growth hormone.
AB  - We report on a 10-year-old Japanese girl with Robinow syndrome accompanied by
      partial growth hormone (GH) insufficiency. We started GH replacement therapy at
      the chronological age of 6.5 years. In this case, improvement in the growth
      velocity was remarkable, but bone maturation accelerated even more. In order to
      avoid further acceleration of bone maturation, we started to treat our patient at
      the chronological age of 9.8 years with GH combined with gonadal suppression
      therapy using a luteinizing hormone releasing hormone analogue. However, no
      improvement in height SDS for bone age was attained. Our observations suggest
      that the indication of GH therapy for patients with Robinow syndrome needs
      careful consideration.

PMID- 9195210
TI  - A case with 47,XXY,del(15)(q11;q13) karyotype associated with Prader-Willi
      phenotype.
AB  - Herein we present the case of a 12-year-old boy who attended our clinic for
      obesity and hyperphagia. As a newborn he was noted to have diffuse muscular
      hypotonia and poor sucking response. At the age of 11 years, he was admitted to
      hospital for respiratory insufficiency. He had personality disorders
      characterized by temper tantrums and violent outbursts including self-mutilation.
      Physical evaluation revealed marked central obesity, he had small hands and feet,
      and also genital hypoplasia. Of the biochemical parameters, hyperglycemia and a
      low serum testosterone level must be emphasized. The patient fulfills the
      clinical criteria of typical Prader-Willi syndrome. Cytogenetic and fluorescence
      in situ hybridization analysis showed a karyotype 47,XXY, del(15)(q11;q13). To
      our knowledge this is the first report of the aforementioned genotype expressed
      as Prader-Willi phenotype in childhood.

PMID- 9195211
TI  - Sustainability of keratinocyte gene transfer and cell survival in vivo.
AB  - The epidermis is an attractive site for therapeutic gene delivery because it is
      accessible and capable of delivering polypeptides to the systemic circulation. A
      number of difficulties, however, have emerged in attempts at cutaneous gene
      delivery, and central among these is an inability to sustain therapeutic gene
      production. We have examined two major potential contributing factors, viral
      vector stamina and involvement of long-lived epidermal progenitor cells. Human
      keratinocytes were either untreated or transduced with a retroviral vector for
      beta-galactosidase (beta-Gal) at > 99% efficiency and then grafted onto
      immunodeficient mice to regenerate human epidermis. Human epidermis was monitored
      in vivo after grafting for clinical and histologic appearance as well as for gene
      expression. Although integrated vector sequences persisted unchanged in
      engineered epidermis at 10 weeks post-grafting, retroviral long terminal repeat
      (LTR)-driven beta-Gal expression ceased in vivo after approximately 4 weeks.
      Endogenous cellular promoters, however, maintained consistently normal gene
      expression levels without evidence of time-dependent decline, as determined by
      immunostaining with species-specific antibodies for human involucrin, filaggrin,
      keratinocyte transglutaminase, keratin 10, type VII collagen, and Laminin 5
      proteins out to week 14 post-grafting. Transduced human keratinocytes generated
      multilayer epidermis sustained through multiple epidermal turnover cycles; this
      epidermis demonstrated retention of a spatially appropriate pattern of basal and
      suprabasal epidermal marker gene expression. These results confirm previous
      findings suggesting that viral promoter-driven gene expression is not durable and
      demonstrate that keratinocytes passaged in vitro can regenerate and sustain
      normal epidermis for prolonged periods.

PMID- 9195212
TI  - Post-transplant methotrexate administration leads to improved curability of mice
      bearing a mammary tumor transplanted with marrow transduced with a mutant human
      dihydrofolate reductase cDNA.
AB  - To test the concept that protection of bone marrow progenitor cells via
      introduction of a drug resistance gene would allow larger and curative doses of
      chemotherapy to be administered, we used mice bearing a transplanted breast
      cancer as a model system. Mice bearing the E0771 tumor were treated with lethal
      doses of cyclophosphamide (CPA) and rescued from toxicity by administration of
      bone marrow transduced with a mutant dihydrofolate reductase (DHFR) cDNA (Ser-31)
      in a retroviral construct. Animals receiving marrow not transduced with mutant
      DHFR cDNA died from methotrexate (MTX) toxicity, whereas mice transduced with
      mutant DHFR cDNA containing marrow were able to tolerate MTX treatment post
      transplant; 44% of the mice had no demonstrable tumor when sacrificed on day 52.
      Another control group of mice treated with CPA and transplanted but not treated
      with MTX post-transplant succumbed to tumor regrowth. These data provide a strong
      rationale for the use of drug resistance genes to protect marrow from drug
      toxicity because the increase in dose tolerated may result in an improved cure
      rate of chemosensitive tumors.

PMID- 9195213
TI  - Keratinocyte gene therapy for adenosine deaminase deficiency: a model approach
      for inherited metabolic disorders.
AB  - Disorders in which there is toxic buildup of circulating substrate may be treated
      by furnishing an enzyme reservoir capable of metabolically processing the excess
      substrate. The epidermal keratinocyte is a potential site for such a reservoir.
      In this study, we explore the capacity of genetically modified keratinocytes to
      metabolize extracellular substrate in a culture model that resembles in vivo
      epidermal architecture. Keratinocytes from adenosine deaminase (ADA)-deficient
      patients were transduced with a retroviral vector encoding the human ADA gene and
      the capacity of this tissue to deaminate deoxyadenosine (dAdo) in vitro was
      measured. The results show that at a substrate concentration of 10 microM, ADA
      corrected keratinocytes deaminate dAdo at a rate of 0.38 nmol/min.10(6) cells.
      These results indicate that keratinocytes process extracellular substrate at
      rates that suggest complete substrate conversion in a single pass. This study
      provides a strong indication that the epidermis, the largest and most accessible
      tissue of the body, is a valuable site for designing clinically relevant gene
      therapies.

PMID- 9195214
TI  - Enhanced distribution of adenovirus-mediated gene transfer to lung parenchyma by
      perfluorochemical liquid.
AB  - Although gene therapy holds great promise for the treatment of inherited and
      acquired diseases of the lung, a number of issues including efficient delivery
      and distribution of genes to pulmonary target cells must still be addressed. In
      this study we evaluated the use of perfluorochemical (PFC) liquid as a vehicle
      for delivery of recombinant adenovirus (AdCBlacZ) to lungs of juvenile rabbits.
      Virus was instilled into trachea of rabbits, and 4 days later the lungs were
      removed, cut into multiple pieces, and assayed for beta-galactosidase (beta-Gal)
      activity. Total lung expression of the beta-Gal reporter gene was increased two-
      to three-fold by instillation of the virus (10(11) particles/kg body weight) in
      saline (1.5 ml/kg) simultaneously with perflubron liquid (15 ml/kg) compared to
      virus+saline alone (control). Uniformity of beta-Gal activity between lobes was
      significantly improved by the PFC liquid. In perflubron-treated lungs
      approximately 45% of the lung pieces had beta-Gal-specific activity values within
      50-150% of the mean specific activity for the total lung, compared to only
      approximately 15% of the pieces in control lungs. More of total lobar beta-Gal
      activity was recovered in the distal lung tissue (approximately two-fold greater
      than controls, p < 0.05). Morphological assessment of X-Gal-stained, fresh-frozen
      lung sections showed increased levels and more complete staining of alveolar wall
      cells in the PFC group. These data indicate that the PFC liquid perflubron
      enhances distribution of virus-mediated gene expression to the lung parenchyma in
      healthy rabbits. PFC liquid may be a useful treatment vehicle for accessing
      distal spaces of the damaged or diseased lung.

PMID- 9195215
TI  - Histochemical staining following LacZ gene transfer underestimates transfection
      efficiency.
AB  - Analysis of LacZ gene expression is conventionally inferred from blue staining
      that results from exposure of the transfected cells or tissue to the substrate 5
      bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). Such histochemical
      staining reports not whether the gene product is present or absent, but where it
      is active. We investigated the hypothesis that identification of activity, as
      opposed to presence, of the enzyme underestimates gene expression following LacZ
      gene transfer. Under conditions optimized for in vitro histochemistry, up to 20%
      of cells stably transfected with nls-LacZ remained unstained by X-Gal. In
      contrast, immunostaining with a monoclonal or a polyclonal anti-beta
      galactosidase (beta-Gal) antibody positively stained 99% of the cell nuclei.
      Following in vivo transfection of naked DNA encoding for nls-LacZ, X-Gal staining
      disclosed 2.7 +/- 1.7 positive nuclei per LacZ-transfected animal, or a
      transfection efficiency of 0.015%. In contrast, immunohistochemical staining
      disclosed 118 +/- 32.7 positive nuclei per transfected animal, yielding a
      transfection efficiency of 0.64% (p < 0.0001 versus X-Gal staining). Thus, 42.9
      times more positive cells were detected by antibody than X-Gal staining. Finally,
      LacZ gene expression following intramuscular gene transfer with an adenoviral
      vector was observed in 7.6% of skeletal muscle cells assessed with X-Gal; anti
      beta-Gal antibody identified 21.8% of cells as being successfully transfected (p
      < 0.0001). Thus, X-Gal histochemistry following gene transfer of constructs
      encoding LacZ may underestimate the anatomic extent of gene expression. The
      superior sensitivity of immunostaining suggests that anti-beta-Gal antibody
      represents the preferred analytical tool for light microscopic evaluation of LacZ
      gene transfer.

PMID- 9195216
TI  - Anti-T cell receptor antibody prolongs transgene expression and reduces lung
      inflammation after adenovirus-mediated gene transfer.
AB  - Replication-deficient delta E1a-E3 adenovirus mediates efficient gene transfer to
      the mouse lung; however it induces a host immune response mediated, in part, by T
      cells. This immune response is associated with loss of transgene expression.
      Monoclonal antibodies (mAb) against the T cell receptor (TCR) complex can inhibit
      both CD4+ and CD8+ T cell responses in vivo and are the most potent anti-T cell
      agents in clinical use. To determine whether such mAbs can be used to prolong
      adenovirus-mediated transgene expression, the vector Av1Luc1 (delta E1a-E3
      recombinant adenovirus encoding the firefly luciferase gene) was administered
      intratracheally to C57BL/6 mice on day 0. Three days prior to adenovirus
      administration (day -3), mice were treated with a single i.p. injection of the
      anti-TCR mAb H57. Controls received phosphate-buffered saline. Animals were
      sacrificed on days 3, 14, 28, and 56 and lungs were assessed for transgene
      expression and histopathology. Luciferase activity decreased markedly in the
      controls by day 14, but was maintained at high levels in animals receiving anti
      TCR mAb. A mild, focal, predominantly neutrophilic inflammation was observed in
      the alveoli of all mice 3 days after virus administration. In PBS-treated
      controls, this inflammation progressed to a moderate to severe multifocal,
      perivascular and peribronchiolar lymphoid infiltration at 14 days. B cells and T
      cells were present in approximately equal numbers, with CD4+ T cells
      predominating over CD8+ T cells by 3- to 28-fold. Treatment with H57 resulted in
      near-complete prevention of the lymphocytic inflammatory infiltrate and increased
      luciferase activity throughout the 56-day study period, in association with TCR
      modulation and T cell depletion. Thus, anti-TCR mAb decreases inflammation and
      prolongs gene expression following adenovirus-mediated gene transfer.

PMID- 9195217
TI  - Intracranial administration of adenovirus expressing HSV-TK in combination with
      ganciclovir produces a dose-dependent, self-limiting inflammatory response.
AB  - Replication-defective adenovirus expressing the herpes simplex thymidine kinase
      gene (H5.010RSVtk) may be useful in treating human gliomas. To determine the
      toxicity of this therapeutic strategy, we injected H5.010RSVtk stereotactically
      into the normal brain of Wistar rats, cotton rats, and rhesus monkeys in
      conjunction with systemic ganciclovir (GCV) at 10 mg/kg per day. In the Wistar
      rat, 5.7 x 10(9) pfu resulted in histopathologic injury consisting of localized
      necrosis, mild gliosis, marked malacia, and focal astrocytosis; however, 1.0 x
      10(8) pfu resulted in only mild gliosis and trace meningitis and approximates a
      "no toxic effect" dose. A dose of 1.0 x 10(9) pfu in both adenoviral immune and
      adenoviral naive cotton rats resulted in similar findings. In the rhesus monkey,
      doses ranging from 1.4 x 10(8) pfu to 1.5 x 10(11) pfu resulted in localized
      gliosis, necrosis, perivascular cuffing, meningitis, and roughly correlated in
      severity with increasing dose. No histologic evidence of toxicity was found in
      non-central nervous system (CNS) tissues, and no virus could be cultured from
      cerebrospinal fluid (CSF), blood, urine, and stool samples. All animals survived
      to prescribed end points without signs of general toxicity or neurologic
      symptoms, except for 2 of the rhesus monkeys, one of which became febrile and the
      other of which developed a grand mal seizure (both subsequently resolved). These
      toxicology studies define the parameters for developing a phase I clinical trial.

PMID- 9195218
TI  - Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after
      Systemic administration and apoptosis of ex vivo-infected pancreatic islet
      allografts and isografts.
AB  - Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a
      limited number of tissues, predominantly activated T lymphocytes. We describe the
      construction and biological activity of a replication-deficient type-5 adenovirus
      encoding murine FasL under the control of the cytomegalovirus (CMV) promoter
      (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with
      adCMV-FasL-infected COS cells. Systemic administration of adCMV-FasL to Wistar
      rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose
      dependent manner within 72 hr, an effect not seen in lpr mice, or animals
      administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also
      undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform
      primary nonfunction when transplanted into syngeneic or allogeneic diabetic
      recipients. These results indicate that adCMV-FasL is a potentially useful tool
      to study Fas/FasL biology.

PMID- 9195219
TI  - Establishment of parameters for optimal transduction efficiency and antitumor
      effects with purified high-titer HSV-TK retroviral vector in established solid
      tumors.
AB  - Suicide gene therapy using the herpes simplex thymidine kinase gene and
      ganciclovir is an attractive strategy for solid tumors. Early animal studies
      involved intratumoral injection of retroviral producer cells or unprocessed
      supernatant to generate an antitumor effect. Xenotransplantation of producer
      cells proved effective in several models, but the crude supernatants from the
      same cells were of insufficient titer to produce antitumor effects. We have
      developed new non-murine producer lines that yield replication-defective
      retroviral vectors encoding thymidine kinase at high titer which are then further
      purified and processed, resulting in pharmaceutical grade retroviral vectors with
      titers of up to 10(8) cfu/ml. Purified, high-titer retroviral preparations were
      injected directly into solid tumors in two syngeneic mouse tumor models.
      Significant antitumor responses and some cures were observed following systemic
      ganciclovir therapy. Assays using monoclonal antibodies to measure thymidine
      kinase protein expression at the single cell level in vitro and in vivo were
      developed so that therapeutic transgene expression could be quantified.
      Intralesional delivery resulted in transduction of over 20% of tumor cells in a
      protocol designed to maximize transduction on the basis of separate analyses of
      route, dosage, and schedule of vector administration. A consensus strategy
      evolved in which the combined effects of increased titer and a longer duration of
      retroviral vector administration interact to maximize transduction efficiency.
      These results indicate that purified high-titer retroviral vectors have the
      potential to transfer effective quantities of therapeutic genes into solid tumors
      in human subjects and highlight some pharmacologic factors that could be valuable
      in the design of clinical gene therapy protocols.

PMID- 9195220
TI  - A retroviral vector that allows efficient co-expression of two genes and the
      versatility of alternate selection markers.
AB  - pZIG(hGCSFR) is a retroviral vector that can co-express two genes and also
      provides alternative selection markers. This retroviral vector has been
      constructed to incorporate an internal ribosome entry site (IRES) element to co
      express two exogenous genes in mammalian cells. Two marker/selection genes have
      been cloned into the vector that not only allow the efficiency of co-expression
      to be quantified but also provide versatility of selection criteria. A cDNA
      encoding the hGCSFR (signaling deficient) was cloned as the 5' cistron, and a
      gene encoding a neomycin-resistance and beta-galactosidase (beta geo) fusion
      protein was cloned as the 3' cistron. The two marker genes cloned in this
      retroviral vector allow the selection and isolation of mammalian cells following
      either transient (by fluorescence-activating cell sorting analysis of hGCSFR
      positive cells) or stable (neomycin resistance) infection with the certainty that
      over 93% of clones will co-express both genes. This novel vector offers a
      versatile retroviral vector that can be potentially used in a wide range of gene
      therapy applications as the gene of interest can be coexpressed with either of
      the marker genes depending on whether the retroviral infection is to be performed
      in vitro, in vivo, or ex vivo.

PMID- 9195222
TI  - The clinical spectrum of type IV collagen mutations.
AB  - Clinical manifestations of type IV collagen mutations can vary from the severe,
      clinically and genetically heterogeneous renal disorder, Alport syndrome, to
      autosomal dominant familial benign hematuria. The predominant form of Alport
      syndrome is X-linked; more than 160 different mutations have yet been identified
      in the type IV collagen alpha 5 chain (COL4A5) gene, located at Xq22-24 head to
      head to the COL4A6 gene. The autosomal recessive form of Alport syndrome is
      caused by mutations in the COL4A3 and COL4A4 genes, located at 2q35-37. Recently,
      the first mutation in the COL4A4 gene was identified in familial benign
      hematuria. This paper presents an overview of type IV collagen mutations,
      including eight novel COL4A5 mutations from our own group in patients with Alport
      syndrome. The spectrum of mutations is broad and provides insight into the
      clinical heterogeneity of Alport syndrome with respect to age at renal failure
      and accompanying features such as deafness, leiomyomatosis, and anti-GBM
      nephritis.

PMID- 9195221
TI  - Phase I study of direct administration of a replication deficient adenovirus
      vector containing the E. coli cytosine deaminase gene to metastatic colon
      carcinoma of the liver in association with the oral administration of the pro
      drug 5-fluorocytosine.

PMID- 9195223
TI  - Mutations in the adrenoleukodystrophy gene.
AB  - Adrenoleukodystrophy (ALD) is a peroxisomal disorder that commonly manifests as
      demyelination of the central nervous system (CNS). The isolation of the ALD gene
      by positional cloning has led to the identification of a variety of mutations in
      the ALD gene. One hundred and ten mutations have been identified to date, of
      which approximately 50% are missense mutations. While rapid DNA-based diagnoses
      of ALD is now possible, there appears to be no simple correlation between
      genotype and phenotype.

PMID- 9195224
TI  - Nine novel L1 CAM mutations in families with X-linked hydrocephalus.
AB  - Mutations in the gene for neural cell adhesion molecule L1 are responsible for
      the highly variable phenotype found in families with X-linked hydrocephalus, MASA
      syndrome, and spastic paraplegia type I. To date, 32 different mutations have
      been observed, the majority being unique to individual families. Here, we report
      nine novel mutations in L1 in 10 X-linked hydrocephalus families. Four mutations
      truncate the L1 protein and eliminate cell surface expression, and two would
      produce abnormal L1 through alteration of RNA processing. A further two of these
      mutations are small in-frame deletions that have occurred through a mechanism
      involving tandem repeated sequences. Together with a single missense mutation,
      these latter examples contribute to the growing number of existing mutations that
      affect short regions of the L1 protein that may have particular functional
      significance.

PMID- 9195225
TI  - DNA repair characteristics and mutations in the ERCC2 DNA repair and
      transcription gene in a trichothiodystrophy patient.
AB  - Patient TTD183ME is male and has typical trichothiodystrophy characteristics,
      including brittle hair, ichthyosis, characteristic face with receding chin and
      protruding ears, sun sensitivity, and mental and growth retardation. The relative
      amount of NER carried out by a TTD183ME fibroblast cell strain after ultraviolet
      (UV) exposure was approximately 65% of normal as determined by a method that
      converts repair patches into quantifiable DNA breaks. UV survival curves show a
      reduction in survival only at doses greater than 4 J/m2. Nucleotide sequence
      analysis of the ERCC2 (XPD) DNA repair and transcription gene cDNA revealed both
      a Leu461-to-Val substitution and a deletion of amino acids 716-730 in one allele
      and an Ala725-to-Pro substitution in the other allele. The first allele has also
      been reported in one xeroderma pigmentosum group D patient and two other
      trichothiodystrophy patients, while the second allele has not been previously
      reported. Comparisons suggest that the mutation of Ala725 to Pro correlates with
      TTD with intermediate UV sensitivity.

PMID- 9195226
TI  - Six novel mutations in the emerin gene causing X-linked Emery-Dreifuss muscular
      dystrophy.
AB  - Mutations in the emerin gene, also referred to as the STA- or EMD-gene, have been
      found to be the cause of X-linked Emery-Dreifuss muscular dystrophy (EMD). For
      the present study an optimized set of primers was designed to amplify and
      sequence each of the six emerin gene exons, including the intron/exon boundaries.
      All emerin gene exons of 30 unrelated EMD patients have been screened by
      heteroduplex analysis. Aberrant patterns of single exons were found in seven
      patients. Direct sequencing of the respective exons revealed six novel mutations
      distributed in the promotor region and exons 3-6 (delta nt -19 to -40; delta AG
      nt 620-621; ins A nt 895; delta AT nt 908-909; C-->A nt 1420; ins TA nt 1570). By
      this study, the first mutations in the promotor region and in exon 5 have been
      identified. Each of the 25 mutations that have been described so far, including
      those from the present study, abolishes the synthesis of functional emerin. The
      mutations were submitted to the EMD Mutation database
      (http://www.path.cam.ac.uk/emd).

PMID- 9195227
TI  - Screening for ESR mutations in breast and ovarian cancer patients.
AB  - In the present study, leukocyte DNA from 143 patients with familial clustering of
      breast and/or ovarian cancer and tumour DNA from 96 breast carcinomas were
      screened for base mutations in the estrogen receptor gene (ESR). Three patients
      with a family history of cancer were carrying a Gly160Cys germline substitution.
      This alteration was also detected in eight (four females and four males) of 729
      controls (366 female, 363 males), indicating that the substitution probably
      represents a polymorphism. However, in the 229 female controls in whom family
      history of cancer was known, one of two who had a sister with breast cancer was
      carrying the variant allele. Hence, a possible clinical significance of the
      glycine into cysteine cannot be completely ruled out and should be further
      investigated. Somatic mutations were not detected in any of the tumours studied,
      and the present data do not provide support for somatic ESR base mutations as an
      important mechanism for hormonal therapy resistance in estrogen receptor-positive
      breast carcinomas.

PMID- 9195228
TI  - Large majority of single-nucleotide mutations along the dystrophin gene can be
      explained by more than one mechanism of mutagenesis.
AB  - The present study reports for the first time on the analysis of the possible
      origin of single-base mutations along the highly mutable human dystrophin gene.
      Seventy-two mutations were considered and analyzed for consistency with the
      "slipped-mispairing" and "hypermutable CpG" models of mutagenesis. Moreover,
      repeated and symmetric elements, which could participate in the formation of
      secondary structures, were searched in each stretch of sequence including a given
      mutant base. Unexpectedly, the frequency of CpG mutations was found less than
      reported for other genes, whereas the frequency of transitions was found to be
      much higher than expected. Base substitutions in CpG dinucleotides that could be
      explained by methylation-mediated deamination were all C-->T transitions. No G-
      >A transitions in CpG dinucleotides were found. A sequence motif, which has been
      shown to act as an arrest site for polymerase alpha, occurred associated with >
      50% of single-base mutations. All the mutations but one can be explained by at
      least two mechanisms of mutagenesis. This would mean that mutation could occur
      with higher probability at a given position, when it might be produced
      independently by different mechanisms. According to the present data, direct or
      inverted repeats seem to play a major role in this context. Therefore, the search
      for repeats along the dystrophin gene might help in identifying potential sites
      of mutation.

PMID- 9195229
TI  - NF1 mutation analysis using a combined heteroduplex/SSCP approach.
AB  - Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder
      characterized predominantly by neurofibromas, cafe-au-lait spots, and Lisch
      nodules. The disease is caused by disruptive mutations of the large NF1 gene,
      with half of cases caused by new mutation. Less than 100 constitutional mutations
      have thus far been published, ranging from very large deletions to point
      mutations. We have pursued NF1 mutation analysis by heteroduplex analysis (HDA)
      and single-strand conformational polymorphism analysis (SSCP) of individual
      exons. We streamlined these techniques to eliminate the use of radioactivity, to
      apply both methods to the same PCR product, and to multiplex samples in gels.
      Applied simultaneously to a set of 67 unrelated NF1 patients, HDA and SSCP have
      thus far identified 26 mutations and/or variants in 45 of the 59 exons tested.
      Disease-causing mutations were found in 19% (13/67) of cases studied. Both
      techniques detected a variety of mutations including splice mutations,
      insertions, deletions, and point changes, with some overlap in the ability of
      each method to detect variants.

PMID- 9195230
TI  - Identification of two novel LDL receptor gene defects in French-Canadian
      pediatric population: mutational analysis and biochemical studies.
AB  - Familial hypercholesterolemia (FH) is at least twofold more prevalent in French
      Canadians from Quebec than in most Western populations. Although our recent data
      confirmed this high frequency of heterozygous FH in our pediatric population with
      hypercholesterolemia, none of the five established molecular defects for the
      French-Canadian population was detected in 29% of the unrelated French-Canadian
      children characterized by a persistent increase in LDL (low density lipoprotein
      receptor) cholesterol and a positive parental history of hyperlipidemia
      (Assouline et al., 1995). To probe for new mutations, six of these molecularly
      undiagnosed children were investigated as index patients. By using single-strand
      conformation polymorphism analysis and DNA sequencing, two novel mutations were
      identified in two of these subjects: (1) 7-base pair (bp) duplication following
      nucleotide 681 (according to the cDNA sequence) in exon 4 (681ins7), which causes
      a frameshift, the introduction of a stop at codon 208, and premature chain
      termination, and (2) A to G change in exon 8 substituting a tyrosine for a
      cysteine at amino acid 354 (Y354C). A third subject carried the recently reported
      exon 10 mutation (Y468X), whereas the remaining three patients demonstrated
      various known polymorphisms with no effect on gene product. Rapid molecular
      assays were developed to detect the two new mutations as well as the Y468X
      mutation. Screening of our cohort showed heterozygosity in 1/88, in 2/88, and in
      2/88 of patients for the 681ins7, the Y354C, and the Y468X mutations,
      respectively.

PMID- 9195231
TI  - Facilitated diagnosis of CMT1A duplication in chromosome 17p11.2-12: analysis
      with a CMT1A-REP repeat probe and photostimulated luminescence imaging.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is a common autosomal dominant
      demyelinating peripheral neuropathy. Most patients with CMT1A have been found to
      have a 1.5 megabase tandem DNA duplication in chromosome 17p11.2-12. Meiotic
      unequal crossover mediated by the CMT1A-REP repeat is a proposed mechanism for
      generation of the duplication in CMT1A and a reciprocal deletion seen in
      hereditary neuropathy with liability to pressure palsies. Testing for the CMT1A
      duplication is frequently the first step in the molecular diagnosis of patients
      with suspected inherited demyelinating neuropathy. We used a 1.0 kb EcoRI-PstI
      DNA fragment (pHK1.0P) from the proximal CMT1A-REP repeat as a probe for Southern
      blot analysis and detected increased gene dosage in CMT1A by determining
      measuring radioactivity ratios with a photostimulated luminescence imaging plate.
      We found that this method is useful for rapid diagnosis of the DNA duplication
      associated with CMT1A.

PMID- 9195234
TI  - Haemolytic uraemic syndrome and thrombocytopenic thrombotic purpura.

PMID- 9195232
TI  - An efficient and reliable multiplex PCR-SSCP mutation analysis test applied to
      the human E-cadherin gene.
AB  - The invasion suppressor gene E-CADHERIN (CDH1) is downregulated in a large
      variety of human carcinomas. Up to now, mutational analysis of the CDH1 gene has
      been described for 325 tumors derived from only four different tissue types. A
      simple but sensitive mutation detection assay is needed to screen many more tumor
      types, possibly bearing E-cadherin inactivating mutations. For that purpose, we
      developed a multiplex PCR-SSCP analysis for all 16 CDH1 exons. Ease of
      experimentation was combined with reliable sensitivity. Indeed, the present
      multiplex analysis reduces the number of manipulations to 50%, while the mutation
      detection turned out to be highly efficient and sensitive.

PMID- 9195235
TI  - Thromboembolic phenomena and the use of the pig as an appropriate animal model
      for research on cardiovascular devices.

PMID- 9195236
TI  - Hemodialysis associated hypoxia extends into the post-dialysis period.
AB  - To investigate whether hypoxia extends into the post-hemodialysis period, nine
      clinically stable-end stage renal disease patients were dialyzed against
      bicarbonate and one against an acetate batch, all with bioincompatible dialyzers.
      None had clinical evidence of cardiopulmonary overload on the day of the study.
      Using an oximeter with internal memory, oxygen saturation was monitored
      continuously at the beginning, during, and for four hours after hemodialysis.
      Hypoxia was defined as oxygen saturation less than 85%. Three patients had no
      hypoxia during or after dialysis. Hypoxia occurred in five patients both during
      and after dialysis, and in two patients only in the post-dialysis period.
      Episodes of hypoxia were of longer duration and severity in post-dialysis period.
      We conclude that significant hypoxia can occur in the post-hemodialysis period.

PMID- 9195237
TI  - A comparison of the dual lumen and coaxial catheters for temporary hemodialysis
      access.
AB  - Percutaneous central venous catheterization can provide reliable temporary
      hemodialysis access. The current study compared the hemodynamic performance of 28
      coaxial catheters to 27 side by side catheters. A total of 675 dialysis sessions
      were evaluated to assess the flow characteristics of these two designs. The
      results demonstrated that the side by side catheter provided greater cumulative
      blood flow with more favorable venous and arterial pressures. Nevertheless, the
      coaxial catheter performed satisfactorily and met the minimum standards for these
      devices.

PMID- 9195238
TI  - Case report of a patient with bilateral renal cell carcinoma successfully
      maintained on continuous ambulatory peritoneal dialysis after bilateral
      nephrectomy.
AB  - We report on a patient who developed bilateral renal cell carcinoma during
      continuous ambulatory peritoneal dialysis for chronic renal failure. He was
      successfully maintained on this type of dialysis after bilateral abdominal
      nephrectomy.

PMID- 9195239
TI  - Multi-purpose mechanical circulatory device.
AB  - A mechanical circulatory assist device for long term use outside the hospital
      setting has been developed. The device can be used for left, right or bi
      ventricular support, and several of the developed technologies are applicable for
      total artificial hearts and non-pulsatile flow systems. The totally implantable
      device is principally designed for left ventricular support with implantation in
      the left hemithorax. The system utilizes transcutaneous energy and information
      transfer sub-systems, and has no percutaneous connections. In vitro durability
      testing has been conducted for periods from 1-4 years. Bovine experiments have
      been conducted with sustained circulation for periods form 1.5 to 96 hours. The
      in vitro and in vivo evaluation to date has demonstrated that the system can
      function effectively as a totally implantable ventricular assist device. The
      transcutaneous energy and information transfer sub-systems provided the ability
      to power, monitor and control the device, without the need for percutaneous
      connections. Design optimization and chronic in vivo evaluation is planned.

PMID- 9195240
TI  - A pivot bearing-supported centrifugal pump for a long-term assist heart.
AB  - A pivot bearing-supported centrifugal blood pump has been developed. It is a
      compact, cost effective, and anti-thrombogenic pump with anatomical
      compatibility. A preliminary evaluation of five paracorporeal left ventricular
      assist studies were performed on pre-conditioned bovine (70-100 kg), without
      cardiopulmonary bypass and aortic cross-clamping. The inflow cannula was inserted
      into the left ventricle (LV) through the apex and the outflow cannula affixed
      with a Dacron vascular graft was anastomosed to the descending aorta. All pumps
      demonstrated trouble free performance over a two-week screening period. Among
      these five studies, three implantations were subjected for one month system
      validation studies. All the devices were trouble free for longer than 1 month.
      (35, 34, and 31 days). After achieving one month studies, all experiments were
      terminated. There was no evidence of device induced thrombus formation inside the
      pump. The plasma free hemoglobin levels were within normal ranges throughout all
      experiments. As a consequence of these studies, a mass production model C1E3 of
      this pump was fabricated as a short-term assist pump. This pump has a Normalized
      Index of Hemolysis of 0.0007 mg/100L and the estimated wear life of the impeller
      bearings is longer than 8 years. The C1E3 will meet the clinical requirements as
      a cardiopulmonary bypass pump. For the next step, a miniaturized pivot bearing
      centrifugal blood pump P1-601 has been developed for use as a permanently
      implantable device after design optimization. The evolution from C1E3 to the PI
      601 converts this pivot bearing centrifugal pump as a totally implantable
      centrifugal pump. A pivot bearing centrifugal pump will become an ideal assist
      pump for the patients with failing heart.

PMID- 9195241
TI  - Immunological consequences of the use of xenogeneic hepatocytes in a
      bioartificial liver for acute liver failure.
AB  - The use of cells from xenogeneic origin in a bioartificial liver can have a
      number of immunological consequences, not only for the cells in the bioartificial
      liver but also for the patient receiving the bioartificial liver treatment. The
      impact of these consequences will depend on the immune status of the patient
      receiving bioartificial liver treatment, the duration and frequency of the
      treatment and on the extent of interaction between the patients blood (or plasma)
      and the xenogeneic liver cells. In an experimental model we infused rats with a
      culture supernatant of pig hepatocytes and demonstrated using Western blots and
      immunohistological techniques that antibodies are raised against the very small
      amounts of the pig hepatocyte-derived proteins present in the culture medium.
      Potential problems of bioartificial liver destruction and the possibility of
      hypersensitivity reactions due to the secretion of xenogeneic proteins into the
      circulation of the patient are discussed. Because the liver has an important role
      in the clearance of immune complexes it is concluded that precautions should be
      taken when (repeated) application of a xenogeneic bioartificial liver in patients
      with liver failure is considered.

PMID- 9195243
TI  - Effects of hyaluronan on cell proliferation and proteoglycan synthesis in rabbit
      ligamental cells.
AB  - The effect of hyaluronan (HA) on cell proliferation and synthesis of proteoglycan
      (PG) in rabbit ligamental cells was examined in vitro. HA promoted the
      incorporation of 35S-sulfate in a concentration-dependent manner, significantly
      at 100 micrograms/ml and upward, without effect on cell proliferation. The
      chromatographic profile of the 35S-labelled materials extracted with 4 M
      guanidine hydrochloride by Sepharose CL-2B was different in the HA-treated cells
      as compared with untreated cells. Although the radioactivities of the low
      molecular fraction peaked at Kav 0.71 did not change, those of the high-molecular
      fraction (Kav 0.30-0.50) increased with treatment of HA. Ligamental cells
      expressed the mRNA of the PG family's versican and aggrecan (large-molecular
      weight PGs), biglycan and decorin (small-molecular weight PGs) in dot blot
      analysis. Although the mRNA expression of aggrecan, biglycan and decorin did not
      change, that of versican increased upon treatment with HA. These findings suggest
      that HA is involved in promoting production of the large-molecular-weight PG
      versican, and in facilitating extracellular matrix formation.

PMID- 9195242
TI  - Qualitative assessment of blood washing with the continuous autologous
      transfusion system (CATS)
AB  - A number of different blood-processing methods can be used at the end of
      cardiopulmonary bypass (CPB) to improve the quality of autologous blood. They
      include centrifugation, hemofiltration and cell-washing. They differ in
      processing time required, cost of disposables and the quality of the processed
      autologous blood product. The newly developed continuous auto-transfusion system
      (CATS: Fresenius AG, Bad Homburg) uses a continuous cell-washing method. In a
      prospective study, the oxygenator blood of 10 patients was processed at the end
      of cardiac surgery with CATS and the quality of autologous blood before and after
      processing was compared. The processing volumes and the time required were
      recorded. The concentrations and elimination rates of blood parameters and waste
      products such as activated coagulation and complement products were measured. At
      the end of CPB a mean volume of 1,010 +/- 174 ml diluted oxygenator blood was
      processed and concentrated to 310 +/- 88 ml in 11.0 +/- 2.2 mins. Cellular
      elements such as erythrocytes and leucocytes were mostly retained and their
      concentration showed a significant increase after processing (250% and 210%
      respectively; p < 0.01). Thus, the blood processing with CATS resulted in an
      excellent hemoconcentration (hematocrit 62 +/- 3 vs. 24 +/- 4% before processing)
      with a consistent reproducibility. On the other hand, the CATS concentrate showed
      a significant loss of autologous plasma proteins. Likewise, all water soluble
      elements such as waste products are significantly lower in concentration after
      processing and, if calculated by quantity, they show a high elimination rate (>
      93%). In conclusion, the continuous autologous transfusion system permits an
      automated, rapid and continuous processing of autologous blood yielding a
      standardised high quality erythrocyte concentrate.

PMID- 9195245
TI  - Tolerability of nabumetone: a pilot in vitro study showing absence of injury to
      articular cartilage.
AB  - Nabumetone, a compound of the naphthylalkanone class, has shown considerable anti
      inflammatory, analgesic and antipyretic effects, together with high systemic and
      organ-specific tolerability. Its reputation for tolerability has been increased
      by an in-vitro study evaluating the mature collagen metabolism's markers under
      nabumetone treatment, which shows that, nabumetone does not interfere with
      collagen synthesis. Therefore, unlike some nonsteroidal anti-inflammatory drugs,
      nabumetone might not be injurious to articular cartilage. This feature makes
      nabumetone even safer for long-term treatment of rheumatic and orthopaedic
      conditions.

PMID- 9195244
TI  - Early changes of liver phospholipase C activity in rats fed an orotic acid
      supplemented diet.
AB  - In this study of the effect of an orotic-acid (O.A.) diet on the activity of
      membrane-bound phosphoinositide-specific phospholipase C (PL-C) of rat liver, its
      enzymatic activity was evaluated in vitro on membranes obtained from the hepatic
      tissue of male Wistar rats fed a diet containing 1% O.A. for 2 and 5 days and
      from control rats. The rate of breakdown of labelled phosphatidylinositol-4,5
      bisphosphate (Ptdins-P2) added to the isolated membranes was measured both in the
      absence and in the presence of guanosine-5'-O-thiotriphosphate (GTP gamma S). The
      enzyme stimulation by bombesin was also analysed. PL-C activity proved to be
      deeply and early modified by O.A. The basal activity was increased 2 days after
      feeding on the O.A.-supplemented diet, but the difference from control rats was
      no more significant after 5 days of this diet. The most interesting changes
      concerned the response to bombesin; the hormone failed to induce any stimulation
      of PL-C in O.A.-treated rats after either 2 or 5 days of diet, whereas it nearly
      doubled Ptdins-P2 breakdown in the liver membranes from control rats. The lack of
      any stimulation of the phospholipase C by bombesin in O.A.-treated rats indicates
      a deep impairment of this signal transmission system; its possible causes and
      consequences are discussed.

PMID- 9195246
TI  - The macrophagic activity of patients affected by pneumonia or chronic obstructive
      pulmonary disease.
AB  - The function of alveolar macrophages (AMS) in patients with pneumonia (n = 7)
      (Group A) and chronic obstructive pulmonary disease (COPD) (n = 11) (Group B) was
      investigated by evaluating the rate of phagocytosis and of the intracellular
      killing. A control group of healthy subjects (n = 8) was also included.
      Phagocytosis frequency (PHF), phagocytosis index (PHI) and intracellular killing
      towards Candida albicans were then evaluated. PHF and PHI were found to be
      significantly (p < 0.05) lower in Group B patients than in the control group,
      while intracellular killing showed a behaviour similar to controls. PHF and PHI
      values observed in the patients of Group A and in the control group did not show
      any significant difference; the intracellular killing rate proved on the contrary
      to be significantly (p < 0.05) lower than that observed in the controls.

PMID- 9195247
TI  - Changes in endogenous lipoperoxidation and antioxidant enzyme status induced by
      cysteine in the substantia Nigra.
AB  - It is generally accepted that reactive oxygen species have a major role in the
      mediation of cell damage and that free sulfhydryl groups are vital in cellular
      defence against endogenous or exogenous oxidants. Modification of cellular
      oxidant/antioxidant balance has been involved in the neuropathogenesis of several
      diseases, e.g., stroke, Parkinson's disease, Alzheimer's disease and
      physiological ageing. An increasingly important area of antioxidant defence is
      based on sulfhydryl chemistry, owing to the role of -SH groups in the function of
      macromolecular structures such as enzymes and cellular membranes. Thiols,
      however, may themselves generate deleterious free radicals. In the present study
      we provide experimental evidence suggesting a selective effect of cysteine in
      promoting reactions of oxidative stress in the brain areas of substantia nigra
      and septum, but not in other different areas which were associated with
      corresponding changes in the activity of antioxidant enzymes.

PMID- 9195248
TI  - Body composition and bone mineral density in competitive athletes in different
      sports.
AB  - Bone mineral density (BMD) of the vertebral spine, appendicular skeleton, and
      whole body was studied in male athletes who chronically trained by different
      forms of skeletal loading. Eighteen subjects performed weight-bearing activity
      (canoeists, n = 18), and 14 performed non-weight-bearing activity (cyclists, n =
      14). Twenty-eight age-matched male students served as non-athletic controls. The
      canoeists had significantly higher spine, pelvic and total body BMD than cyclists
      and controls. No intergroup difference was observed in the BMD of arms and legs
      despite the fact that physical activity of canoeists and cyclists were
      characterized by forceful muscular contractions. It is concluded that weight
      bearing activity is essential to obtain beneficial skeletal effects on total and
      regional bone mass in young subjects.

PMID- 9195249
TI  - Conquering AIDS: a long way to go.

PMID- 9195250
TI  - Communicable diseases threaten European region.

PMID- 9195251
TI  - The nurse's role in creating "youth friendly" health services.
AB  - "Healthy Young People Equals a Brighter Tomorrow" is the theme of International
      Nurses' Day 1997, which nurses worldwide will be celebrating not only on May 12,
      Florence Nightingale's birthday, but throughout the month or even longer. As a
      reminder to continue to promote young people's health, in coming issues INR will
      show how nurses, national nurses' associations (NNAs), groups and organizations
      are actively working to get the health message across to young people.

PMID- 9195252
TI  - Initiating health programmes in schools and communities.
AB  - The role and image of the school nurse has come a long way since the heyday of a
      "matron" dispensing cough medicine. Aside from undertaking everyday tasks to
      ensure student wellbeing, school nurses are initiating specific programmes to
      address the specific needs of pupils.

PMID- 9195254
TI  - An innovative approach to teaching maternal/infant care in Jordan.
AB  - Cultural and religious beliefs in Jordan do not allow male nursing students to
      practice in the female patients' wards, especially in maternity units. Yet a
      maternal and infant care nursing course is a required component of Jordan's four
      year undergraduate nursing curriculum. Below, how a maternal/infant care course
      specific for male nursing students with the aim of teaching related but
      culturally appropriate nursing skills was developed.

PMID- 9195253
TI  - Towards quality and cost-effective health care.
AB  - Although rich cumulative evidence exists on nursing's effectiveness, few
      policymakers and healthcare executives apparently are familiar with it. To make
      such scientific-based knowledge more available so that it can be considered and
      integrated in healthcare policy and reform, the WHO Collaborating Centre at Mount
      Sinai Hospital, Toronto, Canada, complied and reviewed research evidence about
      how nursing services contribute towards cost effectiveness and quality health
      outcomes. Below, a summary of its findings.

PMID- 9195255
TI  - The tarsal tunnel syndrome: evaluation of surgical results using multivariate
      analysis.
AB  - Thirty-four patients with the tarsal tunnel syndrome were treated by
      decompression of the posterior tibial nerve. The condition was bilateral in 3
      cases. There were 9 men and 25 women with an average age at operation of 41
      years. The average follow up was for 3.8 years. Multivariate analysis showed that
      the outcome is influenced, in order of importance, by fibrosis around the nerve,
      the preoperative severity of the condition, a history of sprained ankle, worker's
      compensation, a long history, and heavy work. The results were favourable when
      there was a short history, the presence of a ganglion, no sprains, and light
      work. Measurement of the terminal latency of the medial plantar nerve was
      valuable in assessing recovery. The precise cause of the syndrome and its effect
      on treatment should be considered before operation.

PMID- 9195257
TI  - Measurement of the anteroposterior translation of the humeral head using MRI.
AB  - Anteroposterior translation of the humeral head within the glenohumeral joint was
      investigated using MRI. Ten normal shoulders, 11 recurrent anterior dislocations,
      10 stabilised shoulders after the Putti-Platt operation and one shoulder with
      multidirectional instability, were scanned. The arm was positioned in internal
      and external rotation and in an overhead position. Gradient echo volume
      acquisition scans were carried out, and 22 were suitable for evaluation.
      Consistent results were obtained in the normal shoulders. The unstable and
      unstable shoulders showed higher variance, but there was no significant anterior
      translation in external rotation in any group. The range of external rotation was
      significantly reduced in the unstable and stabilised shoulders. A trend towards
      posterior translation was found in internal rotation with a mean of 1 (+/- 0.44)
      in normal, 0.89 (+/- 1.67) in unstable and 1.6 (+/- 1.4) in stabilised shoulders.

PMID- 9195256
TI  - Osteoarthritis and recurrences after Putti-Platt and Eden-Hybbinette operations
      for recurrent dislocation of the shoulder.
AB  - Thirty-five patients who had operations for recurrent anterior dislocation of the
      shoulder were reviewed, with a further 26 answering a questionnaire; the results
      were not as good as reported by others. The mean follow up was 26.9 years. Ten
      out of 43 patients had recurrent dislocations after the Putti-Platt and 6 out of
      18 after the Eden-Hybbinette operation. Osteoarthritis developed in 15 shoulders
      of 26 patients who were followed-up after the former procedure and in 8 out of 9
      shoulders after the latter. These sequelae depend on the age at the first
      dislocation rather than the number of dislocations. The overall satisfaction rate
      was acceptable for both procedures.

PMID- 9195258
TI  - Factors affecting socket fixation after cemented revision.
AB  - Factors influencing the radiographic outcome of revised cemented sockets have
      been investigated in 360 cases; 70 with radiological signs of failure were
      analysed. The acetabular bone stock at revision and preparation of the acetabular
      floor were the two factors which had a significant influence on the outcome. The
      thickness of the cement mantle around the socket also had an influence. Young
      patients were at a higher risk of failure. The use of a flanged socket and an
      acetabular cement pressuriser appeared to improve the radiographic result, but
      this was not statistically significant.

PMID- 9195259
TI  - Aseptic loosening of BonelocR cemented hip prostheses.
AB  - We present a systematic clinical and radiographic study of 147 patients who had
      total hip replacements from February 1992 to May 1993. BonelocR cement was used
      in 108, and PalacosR cement with gentamicin in 39 patients who had an increased
      risk of infection. At follow-up after 24 to 39 months, 26 cases with BonelocR
      cement had failed; there were no clinical failures in the PalacosR group.

PMID- 9195260
TI  - An acrylic Judet hip prosthesis in a shoulder hemiarthroplasty for thirty-nine
      years--a case report.
AB  - We describe a hemiarthroplasty of the shoulder with an acrylic Judet hip
      prosthesis, inserted after the excision of a giant cell tumour of the head of the
      humerus, which functioned well for 39 years.

PMID- 9195261
TI  - Graft selection in anterior cruciate ligament reconstruction--prospective
      analysis of patellar tendon autografts compared with allografts.
AB  - A prospective study of 73 arthroscopic anterior cruciate ligament reconstructions
      using either a patellar tendon autograft or an allograft was made to assess any
      difference in clinical outcome. Allocation was by availability of an allograft.
      There were 48 autografts and 25 allografts. Evaluation was by clinical
      examination and physical tests. At follow-up 2 years after operation, there were
      no statistically significant differences between the two groups in mobility or in
      physical tests, but KT-1000 evaluation showed a slightly greater anterior
      translation in the autografts at 6 months and one year, although at 2 years the
      allografts developed greater anterior laxity. Cybex testing showed greater
      quadriceps strength at 6 months and one year in the allografts, but at 2 years
      the strength was greater in the autografts. Re-rupture occurred in 3 allografts.
      ACL reconstruction with a patellar tendon allograft does not produce a
      significant functional deficit. Full quadriceps recovery takes 2 years.
      Allografts are not recommended as stability deteriorates with time.

PMID- 9195262
TI  - Recovery of full flexion after total knee replacement in rheumatoid arthritis--a
      follow-up study.
AB  - Twenty-three of 327 patients with rheumatoid arthritis (38 out of 509 knees) had
      primary Yoshino-Shoji total knee replacements between 1984 und 1990 and were able
      to squat fully in the Japanese style after the procedure. Seven had died of
      conditions unrelated to their operations. Of the remaining 16, 5 were able to
      squat fully at follow-up; 2 were unable to do so, but had full passive flexion; 9
      were unable to squat and did not have full flexion. The cumulative survival rates
      of patients able to squat were 82.2%, 65.7% and 47% at 2, 5 and 8 years after
      operation. At follow-up, 3 were able to walk out of doors for less than 30 min, 6
      for 30 min or more and in 7 walking was unlimited. These results suggest that
      daily exercises are important in maintaining full flexion. The absence of
      complications may be due low body weight and limited activity due to the disease.
      patients with rheumatoid arthritis and low body weight can be encouraged to
      regain full flexion after total knee replacement if they wish to do so.

PMID- 9195263
TI  - Resection arthrodesis of the knee in the treatment of tumours--a long-term follow
      up.
AB  - Limb salvage operations using large custom-made prostheses have become the
      treatment of choice for juxta-articular tumours at the knee. Resection
      arthrodesis has been used since the 1920s and offers a satisfactory long term
      solution for young active patients. The good functional results after this
      procedure in 9 patients is presented here. This method should still be considered
      in selected cases.

PMID- 9195264
TI  - Improved wound healing in transtibial amputees receiving supplementary nutrition.
AB  - The objective of this prospective study of matched controls was to find out
      whether supplementary nutrition would improve wound healing and decrease
      mortality in patients undergoing transtibial amputation for occlusive arterial
      disease. The nutritional status of 32 consecutive transtibial amputees was
      assessed and 28 were classified as malnourished. Supplementary nutrition was
      given reaching an average intake of 2098 kcal/day for a total of 11 days. In 24
      patients, at least 5 days of preoperative supplementary nutrition were given,
      followed by postoperative treatment for a total of 11 days. Four patients who had
      an immediate operation were given only postoperative treatment, and 4 were
      excluded. The controls were 32 amputees in another hospital and matching
      procedures were carried out with corrections for diabetes, sex, age, smoking
      habits, previous vascular surgery and living conditions before amputation.
      Healing, including those healed before death in both groups, occurred in 26 of
      the nutrition group compared to 13 in the control group, which was statistically
      significant. Nine patients died within 6 months in the nutrition group compared
      to 14 of the controls (not significant). Malnutrition was present in nearly 90%
      of transtibial amputees and supplementary nutrition improved healing, but not
      mortality.

PMID- 9195265
TI  - Significant roentgenographic parameters for evaluating the flexibility of acute
      thoracolumbar burst fractures. An in vitro study.
AB  - Plain lateral radiographs in a neutral position were studied in ten acute
      thoracolumbar burst fractures produced by high speed impact on three vertebrae
      human cadaveric spine segments. Six linear geometric parameters were measured on
      each film. The ratio of each value in the neutral injured to the intact condition
      was correlated linearly with the motion parameters obtained from post-traumatic
      three-dimensional flexibility data (neutral zone NZ; range of motion ROM).
      Anterior unit height (vertebra+adjacent discs) had the highest correlation with
      the neutral zone and flexibility in all directions, especially flexion-extension
      (NZ, R2 = 0.93; flexion ROM, R2 = 0.86; extension ROM, R2 = 0.79) lateral bending
      (NZ, R2 = 0.83; ROM, R2 = 0.90) and right axial rotation (NZ, R2 = 0.53; ROM, R2
      = 0.86). The deformation ratio (average height to depth) correlated most with the
      neutral zone in left axial rotation (R2 = 0.91) and right lateral bending (R2 =
      0.92). Due to the high correlations obtained, these parameters should be
      evaluated in clinical situations to assess their effectiveness in predicting the
      instability of burst fractures. Ultimately, prospective clinical studies are
      required to verify their clinical utility.

PMID- 9195266
TI  - Biomechanical study of the Grosse-Kempf femoral nail.
AB  - We have carried out a biomechanical study of the forces acting on the Grosse
      Kempf intramedullary nail to determine those which most affect its structure. We
      have used finite element analysis to assess the distribution of compression,
      flexion and torsion forces. The qualitative and quantitative distribution of the
      tension on the surface of the nail has been observed. We have shown that the
      torsional force is most important and it is exerted in the posterior part of the
      nail where there is a change from the unslotted to the slotted section.

PMID- 9195267
TI  - Self-compressive osteotomy of the greater trochanter.
AB  - We have designed a dihedral osteotomy of the greater trochanter which is V-shaped
      with the apex infero-medially. A single screw is used for fixation. The osteotomy
      was used in 24 hips (23 patients), as part of a transtrochanteric approach for
      acetabular reconstruction, carried out for dysplasia or in complicated acetabular
      fractures. There were no cases of nonunion or painful bursitis at an average
      follow up of 20 months. The method provides a stable reduction and bony union
      because of the self-compressive effect of the abductor muscles.

PMID- 9195268
TI  - The immunosuppressive effect of fresh allogeneic bone graft in mice.
AB  - We investigated the immunosuppressive effect of fresh bone allografts after donor
      specific spleen cell transfusion in mice. Allografts from major
      histocompatibility complex incompatible mice were performed one week after the
      transfusion. Cellular and humoral immune responses were recorded by measuring
      alloreactive cytotoxic T-lymphocyte activity and antibody activity. Survival in
      days of a second set skin graft was measured for determining clinical immunity.
      Alloreactive cytotoxic T-lymphocyte activity was stimulated at 17 days (10 days
      after bone grafting) and then suppressed at 31 days (24 days after bone
      grafting). The survival of the second set skin graft was not diminished at this
      time. This outcome indicates that the spleen cell stimulated cellular immune
      response was suppressed after fresh bone allografts, suggesting that these
      allografts have an immunosuppressive effect and induce immunosuppressive actions.

PMID- 9195269
TI  - Albendazole treatment and serological follow-up in hydatid disease of bone.
AB  - Case histories of 9 patients with hydatid disease of bone are presented. All
      except one had undergone previous operations and had received oral albendazole
      (15 mg/kg/day) in 28 day cycles (6 to 18). The efficacy of chemotherapy was
      assessed by serological tests for circulating antigen, immunocomplexes and
      specific antibodies, and by radiography and CT scans. These methods helped to
      evaluate treatment and showed that the long term administration of albendazole
      was effective.

PMID- 9195270
TI  - Malignant transformation of a multiple cartilaginous exostosis--a case report.
AB  - A patient is reported who had multiple cartilaginous exostoses with malignant
      transformation of a pelvic osteochondroma.

PMID- 9195271
TI  - Common errors in the treatment of congenital clubfoot.
AB  - The conservative treatment of clubfeet in newborn babies is detailed, and the
      pitfalls in the treatment are commented.

PMID- 9195272
TI  - Subtalar dislocations. A study of 19 cases.

PMID- 9195273
TI  - Alzheimer's Disease International.

PMID- 9195274
TI  - Mutational and susceptibility genetics are different clinical paradigms.

PMID- 9195275
TI  - Dementia disorders in a birth cohort followed from age 85 to 88: The influence of
      mortality, refusal rate, and diagnostic change on prevalence.
AB  - The prevalence of dementia increased in women (from 31% to 46%) but not in men
      (from 27% to 25%) in a representative birth cohort followed from age 85 to 88.
      The increase was mostly attributed to a higher rate of new cases among women than
      among men. The proportion of moderate to severe dementia increased, and mild
      dementia decreased, mainly because of progression of mild dementias to severer
      forms and because most new cases were of moderate to severe degree. The
      proportion of vascular dementia was 47% at age 85 and 54% at 88 despite a higher
      mortality in vascular than in other dementias. Diagnosis changed to vascular
      dementia in 9 out of 31 cases of Alzheimer's disease because of new
      cerebrovascular events. This study illustrates that prevalence is influenced by
      several factors, such as number of new cases, refusal rate, diagnostic change,
      and mortality. These factors act in different directions and may differ between
      populations.

PMID- 9195276
TI  - Measuring functional competence in older persons with Alzheimer's disease.
AB  - Despite their limitations, mental status tests and self/proxy reports of
      instrumental activities of daily living (IADL) are often used to predict
      functional competence. In contrast, the Assessment of Motor and Process Skills
      (AMPS) is a direct observational assessment of IADL competence. Sixty-four
      community-dwelling elderly (20 Alzheimer's disease [AD] patients and 44
      nondemented) were assessed with the AMPS, the Mini-Mental State Examination
      (MMSE), and the Older Americans Resources and Services (OARS)-IADL. Performance
      on all three assessments was significantly lower for the AD sample. The MMSE did
      not correlate significantly with the AMPS motor ability measures but it
      correlated modestly with the AMPS process ability measures. The OARS-IADL
      correlated significantly with the AMPS motor ability measure for the nondemented
      sample alone. Although mental status and self/proxy assessments provide some
      insight into individuals' IADL competence, direct observation of IADL task
      performance provides additional information regarding the subtle process and
      motor skills changes that occur in progressive dementing conditions.

PMID- 9195277
TI  - Screening for dementia: a preliminary study on the validity of the Chinese
      version of the Blessed-Roth Dementia Scale.
AB  - Blessed-Roth Dementia Scale has been one of the most widely used rating scales in
      dementia. Previous studies indicated that this behavioral assessment scale is a
      useful tool for differentiating elderly subjects with no or minimal intellectual
      decline from those with cognitive deterioration. In the present study, the
      authors examined the validity of the Chinese version of the Blessed-Roth Dementia
      Scale (CDS) in Hong Kong. A total of 106 Chinese subjects were recruited from a
      social center, an old-age home, and psychogeriatric outpatient clinics. At a
      cutoff score of 3 of 4, the CDS achieved a sensitivity of 90.5% and specificity
      of 98.1% in differentiating demented from healthy control subjects. In the
      Chinese population studied, the scale was readily acceptable and considered to be
      an useful adjunct in screening of dementia.

PMID- 9195278
TI  - Mnemonics usage and cognitive decline in age-associated memory impairment.
AB  - To determine predictors of cognitive deterioration, the authors performed
      baseline and 1- to 5-year follow-up (mean +/- SD = 2.5 +/- 1.2 years)
      neuropsychological assessments on 36 persons (mean age +/- SD = 62.1 +/- 8.0;
      range = 50 to 81 years) with age-associated memory impairment. Subjects were
      recruited from a larger group of volunteers, had minimal medical comorbidity, and
      25 of them had a family history of Alzheimer's disease. Baseline age and a
      subjective memory measure indicating reported frequency of mnemonics usage were
      significant decline predictors. Subjects reporting more frequent mnemonics use at
      baseline were more likely to show objective cognitive decline at follow-up.
      Baseline full-scale IQ, educational level, and family history of Alzheimer's
      disease failed to predict decline. These findings suggest that although age is
      the strongest decline predictor in some people with age-associated memory
      impairment, self-perception of memory function may also predict subsequent
      cognitive loss.

PMID- 9195280
TI  - Risperidone for dementia-related disturbed behavior in nursing home residents: a
      clinical experience.
AB  - Many nursing home residents are candidates for antipsychotic pharmacotherapy for
      dementia-related behavioral disturbances that include physical agitation and
      aggression, verbal outbursts, anxiety, and depression. These patients are often
      resistant to or intolerant of standard neuroleptics and are usually receiving
      multiple medications for concurrent psychiatric or medical conditions. New
      medications must be carefully considered because they may interact with
      concurrent medications or aggravate concurrent medical problems. Low doses of
      risperidone may be better tolerated in the elderly because the drug poses little
      risk of extrapyramidal side effects or blood disorders. One hundred and nine
      patients with dementia-related behavioral disturbances were studied in 9 nursing
      homes; most initially received 0.25 to 0.5 mg of risperidone twice daily. Their
      behavior was recorded for up to 6 months on questionnaires completed by a nursing
      staff member at each home. Risperidone was well tolerated overall and nursing
      staff viewed it as helpful in 38 of 100 patients, moderately helpful in 26,
      slightly helpful in 17, and not helpful in 19.

PMID- 9195279
TI  - A prospective study of psychotic symptoms in dementia sufferers: psychosis in
      dementia.
AB  - Eighty-seven out of a clinical cohort of 124 patients with Diagnostic and
      Statistical Manual of Mental Disorders (3rd ed., rev.) dementia were followed up
      at monthly intervals for 1 year. Psychotic symptoms were assessed using the
      Burns's Symptom Checklist, and cognitive functioning was evaluated with the
      CAMCOG. The annual incidence rate of psychotic symptoms was 47%, although many of
      the incident symptoms lasted less than 3 months. Fifty-three percent of patients
      with psychosis experienced resolution of their symptoms. Patients either
      experienced brief or persistent psychotic disorders, with few having an
      intermediary course. Persistent psychosis was significantly associated with a 3
      month duration of symptoms at baseline. Neuroleptics did not significantly
      influence the course of psychotic symptoms.

PMID- 9195281
TI  - Review: pathways to morbidity in carers of dementia sufferers.
AB  - The recent literature on informal carers of dementia patients is reviewed.
      Families bear the major responsibility for such care. The production of "burden"
      in carers is a complex process, involving developmental and cultural factors, in
      addition to the stressors of dementia itself. Also influential are the carer's
      gender, coping style, social network, and the carer's level of intimacy with the
      elder. The interpretation of actual morbidity is complicated by methodologic
      problems. However, carers appear to suffer from at least moderate levels of
      psychological symptomatology. Carers tend to judge their own health to be poorer
      than that of controls. Some studies have also found aspects of caregiving to be
      associated with elder abuse, but this is controversial. Caregiving in dementia
      appears to be at least as stressful as that in chronic physical illness and
      depression. Finally, the implications for service provision and future research
      are considered.

PMID- 9195282
TI  - The social networks of older schizophrenia patients. Clinical Research Center on
      Late Life Psychosis Research Group.
AB  - There is a paucity of research that examines the role of family members and
      friends in the lives of older schizophrenia patients. This study compared 66
      middle-aged and elderly outpatients with 31 normal comparison subjects. Five
      dimensions of social network were assessed: (a) family composition, geographic
      proximity, and frequency of contact; (b) instrumental support; (c) emotional
      support and interpersonal difficulties; (d) role of friends; and (e) use of
      formal service providers as sources of support and assistance. As compared with
      normal subjects, the schizophrenia patients were less likely to be married, less
      likely to have children, more likely to live alone, and had fewer friendships.
      The patients were, however, similar to comparison subjects on the following
      family-relationship variables: frequency of contact, instrumental support
      received, presence of a family confidant, and extent of interpersonal
      difficulties. These findings do not support the stereotype of older schizophrenia
      patients as being estranged from family members. The need for developing
      interventions that use key family members to interface with service providers and
      to monitor treatment compliance and continuity of care is discussed.

PMID- 9195283
TI  - Alcoholism in a geriatric outpatient clinic of Sao Paulo-Brazil.
AB  - Alcohol abuse and dependence are an increasing health problem among the elderly,
      but there is only scanty information about their prevalence and associated risk
      factors in developing countries. The authors set out to evaluate the prevalence
      and associated clinical/demographic features of alcoholism in a sample of male
      elderly subjects attending a Geriatric Primary Health Outpatient Clinic in a
      State University Hospital in the City of Sao Paulo-Brazil. Three hundred four
      patients were assessed with the Brazilian version of the Michigan Alcoholism
      Screening Test and a semistructured questionnaire designed to investigate
      associated features. Lifetime alcoholism was present in 15.1% of the sample,
      although only 4.3% were active drinkers. Patients classified as "cases" were
      younger than their nonalcoholic counterparts (70.61 vs. 73.31), and there was a
      mild, though not significant, excess of Blacks and Mulattos among the former
      (32.6% vs. 15.9%). Cases were also more likely to rely on their family for
      financial support (59.0% vs. 43.5%) and to acknowledge a positive family history
      of alcoholism (51.4% vs. 31.2%). Alcohol abuse or dependence was further
      associated with heavy smoking (58.7% vs. 44.0%). The authors concluded that
      alcoholism in this Brazilian elderly sample was likely to be associated with an
      earlier age at onset of medical problems, financial dependence, Black/Mulatto
      race, smoking, and positive family history of alcohol abuse/dependence. The
      authors suggest that the use of standardized methods of assessment of alcoholism
      in general medical settings may increase the detection of cases and contribute to
      improved health measures for the management of these patients.

PMID- 9195284
TI  - Development of angiogenesis inhibitors for cancer therapy.
AB  - Abundant literature exists demonstrating that tumors are dependent on
      angiogenesis for both tumor growth and invasion. The extent of angiogenesis in
      primary tumors has been demonstrated to be associated with a negative prognosis
      in several tumors including non-small cell lung carcinoma, prostate cancer, and
      in node-negative breast cancer, where angiogenesis is an independent negative
      prognostic factor. These data demonstrate the significance of angiogenesis in
      tumor biology and indicate that it can be utilized as a target for novel
      therapeutic strategies. The recent expansion of knowledge into the specific
      pathways of tumor angiogenesis has provided reagents which can now be utilized to
      provide markers of efficacy of antiangiogenic agents in cancer patients. A
      critical part of the development of angiogenesis inhibitors for cancer therapy is
      the clinical trial strategy. Since these agents are primarily thought to be
      cytostatic, carefully designed trials must be conducted which focus on
      appropriate endpoints and integrate relevant biologic markers to support
      efficacy.

PMID- 9195285
TI  - The preclinical evaluation of angiogenesis inhibitors.
AB  - Angiogenesis is a fundamental process which is required for a number of
      physiological and pathophysiological processes. The field of angiogenesis
      therefore has many therapeutic implications and has progressed rapidly. Many
      strategies have been devised to regulate angiogenesis and several endogenous and
      synthetic inhibitors of angiogenesis have now been identified. These inhibitors
      can be used to treat a number of angiogenesis-dependent diseases and they offer a
      novel means of potently inhibiting tumor growth without significant toxicity or
      drug resistance. Recently, some of these inhibitors have entered clinical trials.
      In this article, I will review methods currently employed in the preclinical
      evaluation of angiogenesis inhibitors and I will discuss some of the implications
      of angiogenesis research.

PMID- 9195287
TI  - Angiogenic factors as tumor markers.
AB  - The process of angiogenesis plays a critical role in tumor growth and metastasis.
      Recently, there has been much interest in the possible use of angiogenic growth
      factors as tumor markers. This paper will review the results thus far of attempts
      at measuring various angiogenic factors in bodily fluids. In the future,
      angiogenic factors will most likely be useful as a monitor of therapy and/or a
      predictor of outcome after cancer has been diagnosed.

PMID- 9195286
TI  - Markers of tumor angiogenesis: clinical applications in prognosis and anti
      angiogenic therapy.
AB  - Numerous studies in many tumor types have demonstrated that quantitation by
      microvessel as a measure of angiogenesis is a powerful prognostic tool. However,
      the ability to exploit tumor angiogenesis as a prognostic marker is limited by
      the methods currently used for capillary identification and quantitation. This
      report critically evaluates all aspects of the techniques and their associated
      problems used for assessing tumor angiogenesis in tissue sections including the
      area of tumor assessed, the vascular parameter measured, the method of
      quantitation, the stratification of patients and the practical utility of
      computer image analysis systems. The potential of angiogenic factors assays,
      proteolytic enzymes, and cell adhesion molecules as surrogate endpoints for
      quantifying tumor angiogenesis are discussed and other methods for quantifying
      tumor angiogenesis are described. The potential clinical applications of these
      angiogenic markers in prognosis, stratification for adjuvant treatments (both
      cytotoxic and anti-angiogenic/vascular targeting) and other aspects of patient
      management is also discussed, particularly design of phase I and II trials.

PMID- 9195288
TI  - Preclinical studies of the combination of angiogenic inhibitors with cytotoxic
      agents.
AB  - TNP-740, minocycline, suramin and genistein have demonstrated antiangiogenic
      activity in various experimental systems. The effect of these agents alone and in
      two agent combinations on the number of intratumoral vessels and response to
      cytotoxic anticancer therapies was assessed in animals bearing the Lewis lung
      carcinoma. Treatment with each of the antiangiogenic agents alone and in two
      agent combinations decreased the number of intratumoral vessels visualized by
      CD31 or Factor VIII staining to 30% to 50% of the number in the untreated control
      tumors. In general, the antiangiogenic agents are more effective adjuvants to
      cytotoxic therapies when used as two agent combinations than as single agents.
      The most effective antiangiogenic combinations were: TNP-470/minocycline > TNP
      470/genistein > TNP-470/suramin. The increases in the response of the primary
      tumor to cyclophosphamide, adriamycin, CDDP, BCNU, x-rays or 5-fluorouracil and
      the lung metastases occur to about the same level with the addition of
      antiangiogenic agents to the therapies. With the treatment combination TNP
      470/minocycline/cyclophosphamide 40% of the animals were cured. The results of
      these studies indicate that antiangiogenic agents can be very useful additions to
      treatment regimens for solid tumors.

PMID- 9195289
TI  - An overview of clinical trials involving inhibitors of angiogenesis and their
      mechanism of action.
AB  - Angiogenesis is a biologic process whereby endothelial cells divide and migrate
      to form new blood vessels. This process is required in physiological conditions,
      but is also a necessary requirement for solid tumors to grow and metastasize.
      Over the last several years, the growth factors that have both a positive and
      negative influence on tumor angiogenesis have been delineated. Interfering with
      tumor angiogenesis was considered a potential therapeutic strategy 25 years ago,
      but only recently have compounds with an ability to interfere with angiogenesis
      entered clinical trials. This review will discuss the first generation of
      angiogenesis inhibitors, their mechanism of action and data from clinical trials.

PMID- 9195291
TI  - Somatostatin analogs: angiogenesis inhibitors with novel mechanisms of action.

PMID- 9195292
TI  - Na(+)-Ca2+ exchanger: physiology and pharmacology.
AB  - The Na(+)-Ca2+ exchanger in the plasma membrane is a bidirectional electrogenic
      ion transporter that couples the translocation of Na+ in one direction with that
      of Ca2+ in the opposite direction. This system is involved in regulation of
      intracellular Ca2+ concentration via the forward mode (Ca2+ extrusion) or the
      reverse mode (Ca2+ influx). There are two types of the plasma membrane Na(+)-Ca2+
      exchanger in an animal, and they are called the cardiac type and rod outer
      segment type. In addition, there is an electroneutral Na(+)-Ca2+ exchanger
      present in mitochondria. Recent studies by the molecular biology technique show
      that there are at least 8 isoforms of the cardiac type (NCX1), and there are two
      other exchangers in the brain (NCX2 and NCX3). Due to new techniques of molecular
      biology and electrophysiology, much evidence is accumulating with respect to the
      structure, mechanism, regulation, and physiological and pathological roles of the
      Na(+)-Ca2+ exchanger. This review summarizes recent progress in this research
      field that is of pharmacological interest.

PMID- 9195293
TI  - Amiodarone induces two different types of disorders in mouse alveolar
      macrophages.
AB  - It has been reported that amiodarone induces disorders of alveolar macrophages
      and pulmonary fibrosis, but the mechanism is not well-understood. This study was
      performed to elucidate the toxic mechanism from the standpoint of cellular
      function. Using alveolar macrophages obtained from a male Slc:ICR mouse, several
      injuries caused by amiodarone were compared to those caused by amantadine and
      mianserin as cationic amphiphilic drugs (CADs). As parameters for the drug
      effects, H(+)-ATPase and acid sphingomylinase activities, cellular pH, cytokine
      and prostaglandin releases, phagocytosis and neutral red uptake were measured.
      Amiodarone decreased H(+)-ATPase activity initially and subsequently increased
      cellular pH and decreased acid sphingomyelinase activity. These changes, which
      were also observed with amantadine and mianserin, were considered to be CAD
      related. Amiodarone increased cytokine and prostaglandin releases and suppressed
      neutral red uptake and phagocytosis. These changes, being not induced by
      amantadine and mianserin, were considered to be specific for amiodarone. The
      above data suggest that amiodarone has two types of toxic effects on alveolar
      macrophages.

PMID- 9195290
TI  - Matrix metalloproteinase inhibitors.
AB  - The matrix metalloproteinases (MMPs) are a family of at least fifteen secreted
      and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade
      all of the components of the extracellular matrix, including fibrallar and non
      fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins.
      MMPs are thought to be essential for the diverse invasive processes of
      angiogenesis and tumor metastasis. Numerous studies have shown that there is a
      close association between expression of various members of the MMP family by
      tumors and their proliferative and invasive behavior and metastatic potential. In
      some of human cancers a positive correlation has also been demonstrated between
      the intensity of new blood vessel growth (angiogenesis) and the likelihood of
      developing metastases. Thus, control of MMP activity in these two different
      contexts has generated considerable interest as a possible therapeutic target.
      The tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring
      proteins that specifically inhibit matrix metalloproteinases, thus maintaining
      balance between matrix destruction and formation. An imbalance between MMPs and
      the associated TIMPs may play a significant role in the invasive phenotype of
      malignant tumors. TIMP-1 has been shown to inhibit tumor-induced angiogenesis in
      experimental systems. These findings raised the possibility of using an agent
      that affects expression or activity of MMPs as an anti-cancer therapy. TIMPs are
      probably not suitable for pharmacologic applications due to their short half-life
      in vivo. Batimastat (BB-94) and marimastat (BB-2516) are synthetic, low-molecular
      weight MMP inhibitors. They have a collagen-mimicking hydroxamate structure,
      which facilitates chelation of the zinc ion in the active site of the MMPs. These
      compounds inhibit MMPs potently and specifically. Batimastat was the first
      synthetic MMP inhibitor studied in humans with advanced malignancies, but its
      usefulness has been limited by extremely poor water solubility, which required
      intraperitoneal administration of the drug as a detergent emulsion. Marimastat
      belongs to a second generation of MMP inhibitors. In contrast to batimastat,
      marimastat is orally available. Both of these agents are currently in Phase I/II
      trials in US, Europe and Canada. Some other new agents, currently in clinical
      trials, have been shown to inhibit MMP production. Bryostatins, naturally
      occurring macrocyclic lactones, have both in vitro and in vivo activity in
      numerous murine and human tumors. In culture, bryostatin-1 has been shown to
      induce differentiation and halt the growth of several malignant cell lines. While
      the exact mechanism responsible for anti-tumor activity is unclear, an initial
      event in the action of bryostatin-1 is activation of protein kinase C (PKC),
      followed by its down regulation. Bryostatin-1 does not directly affect the
      activity of MMPs, but it can inhibit the production of MMP-1, 3, 9, 10 and 11 by
      inhibiting PKC. TIMP-1 levels could also be modulated by bryostatin-1, as it is
      encoded by a PKC responsive gene.

PMID- 9195294
TI  - A comparison of the uricosuric effects in rats of diltiazem and derivatives of
      dihydropyridine (nicardipine and nifedipine).
AB  - The effects of nicardipine and nifedipine on the urinary excretion of urate were
      examined in rats and compared with those of diltiazem. Test drugs were
      administered to urethane-anesthetized oxonate-loaded rats by continuous i.v.
      infusion. Diltiazem (10 micrograms/rat/min), nicardipine (0.3 microgram/rat/min)
      and nifedipine (1.0 microgram/rat/min) caused similar reductions of systemic
      blood pressure and increased total renal blood flow. Diltiazem did not increase
      urine volume significantly. However, this drug produced obvious uricosuria, with
      a significant increase in the ratio of urate clearance to inulin clearance
      (Cua/Cin), which resulted from an increase in Cua, but not from changes in the
      glomerular filtration rate (GFR). Nicardipine had clear diuretic and uricosuric
      effects, with similar increases in Cua and GFR and, thus, no change in Cua/Cin.
      On the other hand, nifedipine did not have any significant effect on the renal
      handling of urate. These results suggest that nicardipine produces uricosuria in
      rats via alterations in renal hemodynamics, while the uricosuric effect of
      diltiazem involves the tubules, as well as alterations in renal hemodynamics.

PMID- 9195295
TI  - Affinity for [3H]iloprost binding sites and cAMP synthesis activity of a 3-oxa
      methano prostaglandin I1 analog, SM-10906, in human platelets and endothelial
      cells.
AB  - SM-10902 ((+)-methyl [2-[(2R,3aS,4R,5R,6aS)-octahydro-5-hydroxy-4-[(E)-(3S,5S)-3-
      hydroxy-5-methyl-1-nonenyl]-2-pentalenyl]ethoxy]acetate) and its free acid, SM
      10906 are new stable 3-oxa-methano prostaglandin (PG) I1 analogs. Their
      affinities for [3H]iloprost and [3H]PGE2 binding sites in human platelets and
      human umbilical vascular endothelial cells were compared with those of the PGI2
      analog iloprost, PGE1 and PGE2 by the radioligand binding assay method. The
      cyclic AMP (cAMP) synthesis activity of these drugs were also determined in human
      umbilical vascular endothelial cells. We found that SM-10906 apparently displaced
      [3H]iloprost binding to the membrane fractions in those cells since the pKi
      values were 6.30 in platelets, 7.52 in vein endothelial cells and 6.31 in the
      arterial endothelial cells. The pKi values of SM-10906 for [3H]PGE2 binding sites
      were significantly lower than those obtained for [3H]iloprost binding. SM-10902,
      which is a prodrug of SM-10906, showed low affinity for [3H]iloprost binding
      sites in those cells. SM-10906 also dose-dependently enhanced the cAMP level in
      the vascular endothelial cells. Thus, these findings indicate that SM-10906 binds
      to [3H]iloprost binding sites and exhibits pharmacological functions such as an
      anti-platelet action and a cytoprotective action in endothelial cells through the
      elevation of intracellular cAMP contents.

PMID- 9195296
TI  - Central regulation of urine production by a selective mu-opioid agonist, [D-Ala2,
      N-Me-Phe4, Gly5-ol]-enkephalin, in rats.
AB  - We have investigated opioid mechanisms concerning regulation of urine production
      in the hypothalamic supraoptic nucleus (SON). In this study, the effect of [D
      Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), a potent selective mu-opioid
      agonist, microinjected into the SON of anesthetized hydrated rats, on the urine
      outflow rate was examined. DAMGO caused a dose-dependent decrease in the urine
      outflow rate with no significant changes in blood pressure nor heart rate. The
      ED50 value for the antidiuresis was calculated to be 0.055 nmol from the dose
      response curve. The antidiuresis elicited by DAMGO (0.1 nmol) was partially
      inhibited by intra-SON pre-injection of naloxone (3 nmol), a relatively mu
      selective opioid antagonist, and timolol (100 nmol), a beta-adrenoceptor
      antagonist, but not by intra-SON pre-injection of phenoxybenzamine (20 nmol), an
      alpha-adrenoceptor antagonist, nor atropine (300 nmol), a muscarinic antagonist.
      Intravenous injection of d(CH2)5-D-Tyr(Et)VAVP (16.7 micrograms), a vasopressin
      receptor antagonist, did not influence the DAMGO-induced antidiuresis. These
      findings suggest that antidiuresis mediated through mu-opioid receptors in the
      SON involves beta-adrenoceptors in the nuclei, but does not involve an increase
      in vasopressin release.

PMID- 9195297
TI  - Inhibitory effects of talipexole and pramipexole on MPTP-induced dopamine
      reduction in the striatum of C57BL/6N mice.
AB  - We have investigated the effects of two novel antiparkinsonian drugs, talipexole
      (Domin) and pramipexole, on MPTP-induced dopamine (DA) reduction in the striatum
      of C57BL/6N mice in comparison with those of bromocriptine. Fifteen days after
      MPTP treatment (25 mg/kg, i.p., given daily for 5 days), the DA content in the
      striatum was decreased to 40-60% of the control value. Among the three dopamine
      receptor agonists, talipexole and pramipexole (1 mg/kg, i.p., once a day for 20
      days) more significantly suppressed the MPTP-induced DA reduction in the striatum
      than bromocriptine (10 mg/kg, i.p., once a day for 20 days). Talipexole did not
      influence [3H]MPP+ uptake into striatal synaptosomes. These results suggest that
      talipexole and pramipexole have a protective effect against MPTP-induced DA
      reduction in the striatum of C57BL/6N mice.

PMID- 9195298
TI  - Low-molecular-weight heparin (dalteparin) demonstrated a weaker effect on rat
      bone metabolism compared with heparin.
AB  - We studied the pharmacological effects of dalteparin (low-molecular-weight
      heparin) and heparin on bone metabolism in rats. After their 28 days of
      consecutive intravenous injections, significant loss of bone weight and mineral
      contents was observed in the heparin-treated rats, whereas dalteparin slightly
      reduced bone mass. By the end of the experiment, the femora of 7 out of 8 rats
      fractured in the heparin (10,000 U/kg/day)-treated group, but none had broken in
      the control and dalteparin-treated groups. Serum osteocalcin levels were
      significantly decreased in the former group. The growth plate width of the tibia
      was increased in a dose-dependent manner, especially in the heparin-treated
      group. Histomorphometric assessment of tibia showed that the osteoid surface and
      mineral apposition rates were significantly reduced in the heparin-treated group,
      whereas the eroded surface was significantly increased in the heparin-treated
      group. The above results suggest that heparin not only augments bone resorption
      but also suppressed bone formation and that dalteparin has a weaker suppressive
      effect on bone formation compared with heparin.

PMID- 9195300
TI  - Intracisternal injection of opioids induces itch-associated response through mu
      opioid receptors in mice.
AB  - We examined whether opioids, especially morphine, would centrally elicit
      scratching in mice and determined some characteristics of the scratch-inducing
      action of opioids. When intracisternally (i.c.) injected, morphine (0.1-3
      nmol/mouse) produced a dose-dependent increase in scratching of the face, but not
      of the ears, head and body trunk. When injected intradermally into the rostral
      part of the back, morphine (at most potent i.c. dose of 3 nmol/mouse or higher)
      did not increase the scratching of the injected site. Facial scratching of the
      mouse induced by i.c. injection of morphine (0.3 nmol/mouse) was almost abolished
      by distraction and by naloxone (1 mg/kg, s.c.). [D-Ala2, N-Me-Phe4, Gly5
      ol]Enkephalin (DAMGO) (0.03-2 nmol), but not [D-Pen2,5]enkephalin (DPDPE) and U
      50,488, dose-dependently elicited facial scratching by i.c. injection. These
      results suggest that morphine and DAMGO increased facial scratching, probably
      mediated by central opioid mu-receptors in mice, and such scratching was due to a
      sensation, probably itching. The present animal model may be useful for analyzing
      opioid-mediated central itching.

PMID- 9195299
TI  - Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2
      ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat
      brain.
AB  - The present study was carried out to clarify whether orally administered 5-{3
      [((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a
      serotonin1A (5-HT1A)-receptor agonist having potent anxiolytic-like and
      antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat
      brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1
      0.5 mg/kg) caused a significant decrease in 3[H]8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe
      nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr
      after administration, and the effective doses were similar to those in its
      anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5
      mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect
      [3H]8-OH-DPAT binding in both sections. These results suggest that orally
      administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated
      in vivo responses such as the hypothermic effect, adrenocortical effect and the
      decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds
      to 5-HT1A receptors in rat brain. In addition, they indicate that repeated
      stimulation of the receptors by the agonists does not affect the number of the
      binding sites.

PMID- 9195301
TI  - Interaction of nitric oxide and the renin angiotensin system in renal
      hypertensive rats.
AB  - We investigated the interaction between nitric oxide and the renin angiotensin
      system in regulating isolated aortic tension and mean arterial pressure in renal
      hypertensive rats (RHR). Acetylcholine (ACh) relaxed aorta precontracted with
      norepinephrine from RHR significantly less than that from normotensive rats (NR)
      (Emax: 34.3% and 86.0%, respectively, P < 0.01). The ACh-induced relaxation was
      significantly enhanced by losartan (P < 0.05) and completely abolished by removal
      of endothelium or NG-nitro-L-arginine methyl ester (L-NAME). ACh lowered the mean
      arterial pressure slightly less effectively in RHR than in NR (6.8 and 13.0 mmHg,
      respectively, at 0.1 microgram/kg), whereas the depressor effect was reduced by L
      NAME (-15.5 and 10.3 mmHg, respectively, at 0.1 microgram/kg), but rather
      enhanced by further treatment with losartan (9.9 (P < 0.05) and 17.3 mmHg,
      respectively, at 0.1 microgram/kg). Angiotensin II induced similar contractile
      and pressor responses in both RHR and NR, and these effects were significantly
      enhanced by L-NAME, except for the pressor effect in RHR. L-NAME induced a
      similar pressor response in RHR and NR (15.9 and 15.2 mmHg, respectively, at 0.1
      mg/kg), the effect being decreased by pretreatment with losartan. Losartan
      induced a depressor response that was smaller in RHR than in NR (34.0 and 48.8
      mmHg, respectively, at 0.3 mg/kg), and the response was significantly reduced by
      L-NAME. These results suggest that nitric oxide interacts with the renin
      angiotensin system to control the vascular tension and systemic arterial
      circulation in RHR.

PMID- 9195302
TI  - Effect of KW-5092, novel gastroprokinetic agent, on the peristalsis in the
      isolated guinea pig ileum.
AB  - We examined the effect of KW-5092, a gastroprokinetic agent with
      acetylcholinesterase inhibitory and acetylcholine release facilitatory
      activities, on the peristalsis of isolated guinea pig ileum. KW-5092 (10(-9)-3 x
      10(-6)M) increased the frequency of the peristaltic wave without changing its
      amplitude. Neostigmine increased the frequency at 10(-7) M, but domperidone (10(
      8)-3 x 10(-6)M) had no effect on the peristalsis. The present results suggest
      that KW-5092 enhances the peristalsis via the inhibition of acetylcholinesterase,
      resulting in the intestinal propulsion.

PMID- 9195303
TI  - alpha-adrenoceptor subtype in the hypothalamic paraventricular nucleus involved
      in the regulation of urine production: comparison between Wistar Kyoto and
      spontaneously hypertensive rats.
AB  - Microinjections of alpha-adrenoceptor agonists into the paraventricular nucleus
      (PVN) of Wistar Kyoto rats (WKY) decreased the urine outflow rate in dose- and
      time-dependent manners. The order of the antidiuretic potency is norepinephrine
      (an alpha-agonist) > phenylephrine (an alpha 1-agonist) > > clonidine (an alpha 2
      agonist). The phenylephrine-induced effect was inhibited by WB4101 (an alpha 1
      antagonist), but not by yohimbine (an alpha 2-antagonist). d(CH2)5-D-Tyr(Et)VAVP
      (a vasopressin antagonist) blocked the antidiuretic effect of phenylephrine. In
      spontaneously hypertensive rats (SHR), norepinephrine and phenylephrine produced
      weaker antidiuretic effects than in WKY. These findings suggest that the alpha 1
      subtype of the PVN decreases urine production mediated through vasopressin
      release. This mechanism is more feeble in SHR than WKY.

PMID- 9195304
TI  - Effect of lecithinized-superoxide dismutase on the rat colitis model induced by
      dextran sulfate sodium.
AB  - Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin
      derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half
      life in blood and higher cell affinity than unmodified SOD. The effects of PC-SOD
      were evaluated using the rat ulcerative colitis model induced by 3% dextran
      sulfate sodium. Intravenous injection of rats with 0.5 or 1 mg/kg of PC-SOD
      suppressed the progression of bloody stools, the formation of erosion, and the
      infiltration of the colon with inflammatory cells. Furthermore, it also reduced
      the increase of leukocytes in blood. Thus, PC-SOD may have therapeutic potential
      in the treatment of ulcerative colitis.

PMID- 9195305
TI  - Possible mechanisms underlying the suppression of gastric vagal afferents due to
      ecabapide (DQ-2511), a gastroprokinetic agent, in rats.
AB  - We examined the implication of a nitric oxide (NO)-guanosine 3',5'-cyclic
      monophosphate (cGMP) cascade in the suppression of gastric vagal afferents due to
      ecabapide in anesthetized rats using a standard extracellular method of multi
      unit recording. Sodium nitroprusside (SNP, 0.5 mg/kg), an NO donor, depressed the
      afferent discharge rate of the vagus nerve, like ecabapide (60 micrograms/kg). On
      the other hand, NG-nitro-L-arginine (L-NNA, 5 mg/kg), an NO biosynthesis
      inhibitor, significantly elevated its discharge rate. Pretreatment with L-NNA
      completely blocked the action of ecabapide. Atropine (0.05 mg/kg), a competitive
      antagonist of muscarinic cholinoceptors, showed no effect on the afferent firing.
      These results suggest that ecabapide may suppress the activation of vagal
      afferents in gastric inhibitory vago-vagal reflex pathways through the NO-cGMP
      cascade.

PMID- 9195306
TI  - FR149175, a beta 3-adrenoceptor-selective agonist, is a possible therapeutic
      agent for non-insulin-dependent diabetes mellitus.
AB  - We examined whether FR149175 (ethyl-[(S)-8-[(R)-2-(3-chlorophenyl)-2
      hydroxyethylamino]-6,7,8,9 - tetrahydro-5H-benzocyclohepten-2-yloxy]acetate
      monohydrochloride monohydrate), a selective agonist for the beta 3-adrenoceptor,
      is a possible therapeutic agent for non-insulin-dependent diabetes mellitus
      (NIDDM). FR149175 had hypoglycemic effects with an increase in the level of
      plasma insulin in normal rats. In Zucker fatty rats, an animal model of NIDDM,
      repeated administration of the drug improved hyperinsulinemia and showed a
      tendency to decrease the area under the curve (AUC) for plasma glucose levels in
      the glucose tolerance test. Moreover, FR149175 decreased plasma triglyceride,
      free fatty acid and total cholesterol levels in the rats. Body weight gain in the
      rat was suppressed by FR149175 as well. These results suggest that FR149175 has
      antiobesity and antidiabetic effects and that this drug may be useful for
      treating NIDDM.

PMID- 9195307
TI  - Acetylcholine-induced relaxation of rat aorta is greatest during estrus in the
      sexual cycle.
AB  - Acetylcholine (ACh)-induced relaxation in the aortae precontracted with
      norepinephrine was significantly enhanced in the aortae from estrus (E) rats,
      compared with that in those from metestrus (D-1), diestrus (D-2) and proestrus
      (PE) rats. NG-Nitro-L-arginine methyl ester (L-NAME) inhibited the endothelium
      dependent relaxation in E rats. These results suggest that there is a difference
      in ACh-induced relaxation of the thoracic aorta during the sexual cycle of rats,
      and the relaxation is greatest in E of the sexual cycle; this may be due to a
      difference in nitric oxide synthesis in the endothelium in the sexual cycle.

PMID- 9195308
TI  - Suppression of ischemic edema in mice by manganese-hyaluronate conjugate.
AB  - Manganese-hyaluronate conjugate (Mn-HA) was synthesized from a
      diethylenetriaminepenta-acetic acid derivative of hyaluronic acid and manganese
      ion. The conjugate markedly scavenged super-oxide anion in vitro and exhibited
      much higher anti-inflammatory activity than superoxide dismutase in suppressing
      paw edema in mice when intravenously injected 30 min before the initiation of
      ischemia.

PMID- 9195309
TI  - Analysis of dissociated single neurons by simple and semi-quantitative RT-PCR
      (reverse transcription and polymerase chain reaction).
AB  - We have developed a simple and semi-quantitative method for mRNA determination in
      single cells using the reverse transcription and polymerase chain reaction (RT
      PCR). The distinct features of this method are the highly efficient RNA harvest
      from whole dissociated cells and the ability to perform all RT procedures in one
      tube that allowed semi-quantitative determination of mRNA in dissociated cells.
      This method revealed that histamine H1-receptor mRNA was highly expressed in 5/28
      small and 1/26 large dorsal root ganglion neurons of the mouse.

PMID- 9195310
TI  - Functional leg-length inequality following total hip arthroplasty.
AB  - A consecutive series of 100 patients undergoing primary total hip arthroplasty
      were assessed for functional leg-length inequality (FLLI). In addition, the
      medical records of all patients treated for FLLI by the senior author (C.S.R.) in
      the past 15 years was reviewed. A questionnaire was distributed to the members of
      the Hip Society specifically to query the prevalence, etiology, and management of
      FLLI. Fourteen percent of patients were noted to have pelvic obliquity and FLLI.1
      month after surgery. All had resolution of the symptoms by 6 months after
      surgery. Nine patients have been identified over the past 15 years with
      persistent FLLI. Among the causes suggested by respondents to the questionnaire
      are tightness of periarticular soft tissues with resultant pelvic obliquity and
      degenerative conditions of the spine with contracture. Methods of treatment and
      prevention are discussed.

PMID- 9195311
TI  - Maintenance of proximal bone mass with an uncemented femoral stem analysis with
      dual-energy x-ray absorptiometry.
AB  - Bone ingrowth into uncemented femoral implants with proximal porous coatings has
      been designed to avoid proximal stress shielding and preserve femoral strength.
      Dual-energy x-ray absorptiometry allows repeated quantitative analysis of
      anteroposterior scans of the proximal femur. By use of dual-energy x-ray
      absorptiometry and qualitative radiographic changes, 31 total hip arthroplasties
      with an individually designed, proximally porous-coated prosthesis were evaluated
      after surgery and at intervals up to 2 years. All implants appeared to achieve
      successful bone ingrowth and subsequent remodeling. At the most proximal level
      around the neck osteotomy, the postoperative loss of bone density at 6 months was
      -14.5%, which persisted at 24 months with -11.6%. At the level of the distal
      portion of the porous coating in the lower metaphysis, the density change was 
      8.7%, but bone had remodeled at 24 months with a change in density of only -1.0%
      compared with the immediate postoperative scan. With a design that results in
      reliable proximal ingrowth, this study predicts that after an initial decline in
      bone density, a positive bone remodeling response occurs that could lead to long
      term stable fixation of the femoral implant.

PMID- 9195312
TI  - Effect of a stemless femoral implant for total hip arthroplasty on the bone
      mineral density of the proximal femur. A prospective longitudinal study.
AB  - After total hip arthroplasty with a medullary stem, significant loss of bone
      mineral density (BMD) has been demonstrated in the proximal-medial femoral
      cortex. In an attempt to prevent bone loss, a stemless femoral component was
      designed. Owing to promising experimental results, a prospective clinical trial
      was undertaken in a limited group of patients, all below the age of 50. Yearly
      BMD measurements were carried out in the vicinity of the implant and compared
      with the BMD values obtained in the immediate perioperative period and with the
      values on the unaffected side. The follow-up period in this study was 4 to 6
      years, involving 32 hips in 31 patients. Maintenance of BMD in the operated femur
      was demonstrated. A statistically significant increase in the BMD of the proximal
      medial femoral cortex was observed in those patients who had low initial values.
      In active patients with a life expectancy greater than 30 years, preservation of
      the proximal bone stock after total hip arthroplasty appears beneficial, as these
      patients are most likely to need revision surgery, which is more difficult if
      significant bone loss has occurred. The data further reinforce the crucial role
      of mechanical stress in BMD maintenance.

PMID- 9195314
TI  - Patients' expectations and satisfaction with total hip arthroplasty.
AB  - Although there have been many studies focusing on the increasingly important
      assessment of patients' satisfaction, few studies have specifically addressed
      this tissue for total hip arthroplasty (THA). The goals of this study were to
      measure patients' satisfaction with THA and to evaluate the relationships of
      expectations and outcome to patients' satisfaction. A total of 180 patients were
      surveyed 2 to 3 years after THA about their experiences with THA. Patients cited
      45 different expectations, which were grouped into five categories reflecting
      improvement in pain, walking, psychological state, essential activities, and
      nonessential activities. Overall, 89% of patients were satisfied with the results
      of surgery. Lower rates of satisfaction were found in patients who had a better
      preoperative condition (as measured by the surgeons with The Hospital for Special
      Surgery Hip Scale), in patients who expected improvement in nonessential
      activities, and in patients who reported worse postoperative condition (as
      measured by self-assessment with the Hip Rating Questionnaire and the Medical
      Outcomes Study Short-form General Health Survey). Patients were also asked how
      they came to THA. Nearly 50% of patients were first referred to an orthopaedist
      by family or friends or based on their own knowledge. Seventy-four percent either
      had subsequently referred others for THA or would have done so if they knew
      someone with hip pain. This study demonstrates that satisfaction with THA is a
      complex phenomenon, affected by expectations, outcome, and what patients know
      about the procedure from their community network. A better understanding of THA
      satisfaction will enable better future selection of patients and an additional
      dimension of outcome, both of which are important to patients and payers.

PMID- 9195313
TI  - Bone scintigraphic appearance of asymptomatic hydroxyapatite-coated hip
      arthroplasties.
AB  - To obtain information about the bone scintigraphic appearance of a hydroxyapatite
      (HA)-coated proximal femoral implant, this examination was performed on 24
      patients with a clinically and radiologically successful femoral implant in hip
      arthroplasty. The prosthesis had a proximal HA coating for supplementary
      fixation. The patients' mean age was 50.3 years (range, 28-65 years) at
      operation. The interval from the operation to the scintigraphy ranged from 6
      months to 5.5 years (mean, 2.2 years). Scintigraphy was performed using 99mTc
      medronic acid. Quantitative counts were recorded in 4 zones: 3 along the length
      of the implant (trochanteric region with HA coating, midprosthesis, and distal
      tip) and 1 below the prosthesis. The results were expressed as ratios using the
      nonoperated femur as a control value. The results demonstrated that the mean
      activities in all 4 zones were increased relative to the untreated side. The
      highest activity was observed in the region around the prosthetic tip, with an
      elevation of 46% above the control value. This activity showed a significant
      decline over time. The counts recorded in the trochanteric region, where the
      implant was coated with HA, were 20% above the control value and similar to those
      seen in its adjacent noncoated midprosthetic region. In the trochanteric region,
      however, the activity did not show a decline over the follow-up period.

PMID- 9195315
TI  - Causes of death after hip arthroplasty in primary arthrosis.
AB  - The causes of death in 1,018 patients operated on for primary osteoarthrosis with
      cemented total hip arthroplasty (THA) were compared with those of age- and sex
      matched orthopaedic control patients and those of the general population in
      Finland. The mean follow-up period was 12 years for the THA patients and 11 years
      for the control patients. During the first 4 years after surgery, the mortality
      of the THA patients from circulatory diseases was significantly increased
      compared with that of the orthopaedic control patients; the number of deaths in
      patients with THA was 34 compared with 17 for orthopaedic control patients, the
      relative risk being 2.00 (95% confidence interval, 1.13-3.54). During the 10-year
      period after the surgery, the relative risk of death of the THA patients compared
      with the orthopaedic control patients was 1.50 for death from circulatory
      diseases (95% confidence intervals, 1.11-2.00), 0.42 for accidental death (95%
      confidence interval, 0.55-1.08), 0.74 for death from cancer, and 0.77 for death
      from other causes. The observed numbers of deaths from circulatory diseases or by
      accidents for patients with THA during a postoperative time frame of 5 to 23
      years did not differ from the numbers expected for an age- and sex-matched
      subgroup of the Finnish population. The number of deaths from cancer was less
      than expected (P = .046).

PMID- 9195317
TI  - Visual analog scale for the assessment of total hip arthroplasty.
AB  - The use of a visual analog scale (VAS) for the assessment of total hip prostheses
      was evaluated in 54 patients (58 hips), on average 3.4 years following operation.
      The Harris hip scores were determined in each case and the patients were also
      asked to record their overall assessment of their new hips on a VAS. Five
      patients (6 hips) were unable to understand and use the VAS. For the remaining 49
      patients (52 hips), the Harris hip score averaged 84 (41-100) and the VAS score
      75 (2-100). There was a high correlation between the Harris hip scores and the
      VAS scores (+0.84). Use of a VAS provides a simple and reliable basis for the
      assessment of a total hip arthroplasty.

PMID- 9195316
TI  - Cementless revision of total hip arthroplasty using the anatomic porous
      replacement revision prosthesis.
AB  - This study reports the results of revision total hip arthroplasty with the
      Anatomic Porous Replacement Revision Hip System (Intermedics Orthopedics, Austin,
      TX) to investigate the value of cementless fixation. Sixty-six hips in 65
      patients were followed for a mean of 4.7 years in patients with a mean age of 56
      years. Thirty-six patients were categorized as Charnley class A, 16 as class B,
      and 13 as class C. Forty (61%) of the femurs were classified before surgery as
      having loss of bone distal to the intertrochanteric line. Thirty-two (48%) of the
      femurs required augmentation with demineralized strut cortical allografts, 5 (8%)
      required bulk femoral allografts, and 12 hips (18%) required acetabular
      allografts. Overall, 4 stems (6%) and 2 acetabular components (4%) required
      further revision surgery. The reason for further revision in 1 stem and both
      acetabular components was allograft failure. Fifty-six (85%) hips had excellent
      or good Harris hip scores. Ninety percent of hips had no or slight pain, and 90%
      allowed patients to walk with no or slight limp. Those hips that had
      hydroxyapatite coating added to the porous coating had statistically improved
      Harris hip scores for both pain and limp. Stable fixation was present in 95% of
      stems. Demineralized strut grafts healed in 30 of 32 hips. Thirty-nine of 44
      noncemented revision sockets had no radiolucent lines and there were no loose
      components. Cementless fixation was effective for these hips.

PMID- 9195318
TI  - Results and complications of total hip arthroplasties in patients with sickle
      cell hemoglobinopathies. Role of cementless components.
AB  - The complications and results of 16 primary and revision total hip arthroplasties
      in patients with sickle-cell hemoglobinopathies were evaluated. One patient died
      from renal failure at 1 year, leaving 15 hips in 10 patients for review at a mean
      follow-up period of 6 years (range, 2-12 years). There were 7 cementless primary
      total hip arthroplasties and 8 revision arthroplasties, 6 of which were
      uncemented. Patients were evaluated clinically using a standard hip rating system
      and radiographically using accepted criteria. There were no early or late deep
      infections; however, 7 of 8 primary arthroplasties and 5 of 8 revisions had one
      or more early complications. No cementless component demonstrated loosening;
      however, there was asymptomatic polyethylene wear in 2 primary arthroplasties,
      treated with grafting and liner exchange, and femoral osteolysis was present in 4
      of 13 cementless arthroplasties, one of which was revised to permit extensive
      grafting. Of the original 15 arthroplasties performed by the senior author, 5
      required some type of reoperation during the study. At most recent follow-up
      evaluation, no component in the study was radiographically loose. In the hips
      that did not require reoperation, the overall results were excellent in 6 hips,
      good in 3, and poor in 1 hip. Of the 5 hips requiring reoperation, the results
      were excellent in 3 hips, good in 1, and fair in 1 hip at most recent follow-up
      evaluation. Cementless components should be considered for all primary and
      revision arthroplasties in patients with sickle-cell hemoglobinopathies, but
      early complications are frequent and a high incidence of polyethylene wear and
      osteolysis requiring reoperation may be expected.

PMID- 9195319
TI  - Multiple irrigation, debridement, and retention of components in infected total
      knee arthroplasty.
AB  - The results of 24 infected total knee arthroplasties (22 patients) that were
      treated by irrigation, debridement, and retention of the prosthetic components
      were prospectively studied. Strict criteria were used for the selection of this
      method of treatment. Patients had to be less than 30 days after index
      arthroplasty (postsurgical group) or had to have less than 30 days of knee
      symptoms (hematogenous group). In addition, there had to be no radiographic signs
      of osteitis or evidence of a loose prosthetic component. Patients had one to
      three irrigation and debridement procedures depending on systemic signs, knee
      symptoms, or the results of knee aspirations. All of the immediate postsurgical
      infections (10 knees) and 10 of the 14 (71%) late hematogenously infected knees
      retained the prosthesis without further evidence of infection at the final follow
      up visit at 48 months (range, 24-140 months). This study shows that in selected
      circumstances, irrigation, debridement, and retention of the components can
      result in low morbidity with high success rates.

PMID- 9195320
TI  - Effect of a centralizing device on cement mantle deficiencies and initial
      prosthetic alignment in total hip arthroplasty.
AB  - Sixty consecutive patients undergoing a primary hybrid total hip arthroplasty
      were randomized to receive a femoral component either with or without a distal
      centralizing device. The group with a centralizer had significantly fewer
      patients with cement mantle deficiencies (excessively thin areas of cement) than
      the group without a centralizer (P < .001). Furthermore, the centralizer group
      was, on average, in a neutral alignment, whereas the group without a centralizer
      was in a varus alignment (P < .001). It was concluded that the distal
      centralizing device significantly decreases the incidence of cement mantle
      deficiences and reproducibly aids in achieving a more neutral prosthetic
      alignment.

PMID- 9195321
TI  - Three-dimensional morphology of the proximal femur.
AB  - In the field of uncemented hip arthroplasties, secondary biologic fixation of
      femoral implants depends directly on the quality of the primary stability.
      Metaphyseal filling and a good fit between the implant and the proximal femur
      improve initial stabilization and optimize the transmission of forces to the
      bone. Precise knowledge of the three-dimensional femoral shape is essential to
      the design and selection of adapted implants. Three hundred ten femurs in 300
      patients suffering from primary hip osteoarthritis were analyzed by computed
      tomography scanning. After three-dimensional reconstruction, several measurements
      were extracted, and the parameters essential to the characterization of the
      diverse femoral morphologies encountered were identified. A new classification of
      the proximal femur is proposed. The consequences on the design and the
      preoperative selection of femoral implants are discussed.

PMID- 9195322
TI  - Effects of grafting on porous metal ingrowth. A canine model.
AB  - Twenty-five mongrel dogs were studied using implantation of autograft, fresh
      frozen allograft, and beta-tricalcium phosphate around a porous-coated chrome
      cobalt plug in the distal femoral metaphysis; interference-fit and overreamed
      control specimens were also studied. Over the course of this 4-month study, bone
      ingrowth through the grouting materials into the center plug was noted for
      autologous, allograft, and ceramic specimens. Quantitatively, in terms of push
      out strength and histology, there were no significant differences between grafted
      groups; significantly higher push-out strengths were attained in each grafted
      subgroup compared with nongrafted, overreamed control subjects. In the setting of
      uncemented revision total hip arthroplasty, bone-grafting is frequently required.
      Because of the limited availability of autogenous bone and the potential
      liabilities of allograft material, attention has been given to bone substitutes.
      On the basis of this preliminary study, bone ingrowth into a porous metal
      substrate has been documented to occur through autograft, allograft, or ceramic
      grouting agents. Within the limits of this nonloaded experimental model, it
      appears that these materials are comparable in terms of their osteoconductive
      capability. Even in the optimal laboratory situation, bone ingrowth does not
      appear to occur in a canine model across a nongrafted 2-mm gap with regularity
      over a 16-week period.

PMID- 9195323
TI  - Bone-membrane interface in aseptic loosening of total joint arthroplasties.
AB  - In 19 patients who underwent revision arthroplasty for aseptic loosening of total
      joint arthroplasty, specimens were taken at the time of operation to include the
      bone-membrane interface. In 16 (84%) of the specimens, sufficient visualization
      of the interface was possible to allow histologic interpretation. In 13 of these
      cases, there was prominent evidence of classic bone remodeling with osteoclast
      mediated resorption and active new bone formation. These results suggest that the
      osteolysis in aseptic loosening is mediated through osteoclastic bone resorption
      and that the bone found in such areas is extremely active. The findings help to
      explain the efficacy of impacted morselized bone-graft in the treatment of bone
      lysis in aseptic loosening.

PMID- 9195324
TI  - Arthroscopic debridement versus arthroplasty in the osteoarthritic knee.

PMID- 9195325
TI  - Tissue expansion for staged reimplantation of infected total knee arthroplasty.
AB  - Resection arthroplasty of a chronically infected total knee arthroplasty resulted
      in thin and contracted anterior skin. Expansion of skin using Silastic reservoirs
      (McGhan Medical, Santa Barbara, CA) facilitated wound closure and rehabilitation
      following staged total knee reimplantation. Prophylactic expansion of skin around
      the knee avoided salvage soft tissue procedures such as local and distant tissue
      flaps.

PMID- 9195326
TI  - Tissue expansion prior to revision total knee arthroplasty.
AB  - The first case of the use of a tissue expander in revision total knee surgery is
      reported. A 76-year-old woman presented with extremely adherent scare tissue on
      the anterior proximal tibia that was the result of multiple debridements and skin
      grafting for an infected primary total knee arthroplasty. The tissue expander was
      placed prior to subsequent revision total knee arthroplasty to permit complete
      excision of the scar and to provide tension-free closure with normal skin at the
      time of revision. Three years after the surgery, the patient is doing well.

PMID- 9195327
TI  - Awareness and perceptions of a hospital's closed-circuit TV channels.
AB  - Closed-circuit television (CCTV) programs are used in many hospitals for patient
      education and entertainment. However, few studies have addressed how patients
      perceive CCTV programs and whether the educational and entertainment objectives
      have been satisfied. We studied these questions by surveying patients from a
      major suburban teaching hospital. We found that when care providers recommended
      viewing, patients were more likely to watch and to perceive the programs as
      valuable.

PMID- 9195328
TI  - Strictly from Hungerford: what medical and scientific artists should know about
      philosophy.

PMID- 9195329
TI  - The use of color in scientific and medical illustration. Part II: Form.
AB  - The medical illustrator is confronted with the problem of accurately representing
      three-dimensional form, more than most other illustrators or graphic artists.
      Often the illustrator who feels competent when working achromatically finds
      himself feeling insecure when attempting a full-color illustration. With some
      illustrators, a sense of color seems to be inborn. However, for those who do not
      feel secure about their own innate sense of color, it should be very encouraging
      to learn that the general principles of using color effectively and accurately to
      depict form have been laid down by generations of artists and can be learned.
      Moreover, the technique of observing and analyzing the ways that color is
      modulated by form can also be learned.

PMID- 9195330
TI  - Rheological studies on the solubilization by the surfactant SDS of complexes
      between three acidic polysaccharides and an organic base chloride.
AB  - Developments in the solubilization of complexes between the cationic polymer,
      poly(hexamethylenebiguanidinium chloride) (PHMBH+Cl-) and acidic polysaccharides
      are reported. It was discovered that the anionic detergent sodium dodecyl
      sulphate (SDS) is an excellent solubilizer for these complexes, enabling several
      multi-component systems to be studied. SDS itself was shown to interact with
      PHMBH+Cl- to form a highly viscous solution. Maximum viscosity was obtained with
      a SDS:PHMBH+Cl- molar ratio of 15.6. SDS:PHMBH+Cl- at this ratio served as a good
      solubilizer for the acidic polysaccharides (sodium alginate, sodium carboxymethyl
      cellulose, and xanthan), forming highly viscous fluids. The effect of temperature
      on the viscosity of these solutions was also examined.

PMID- 9195331
TI  - Comparative bone healing near eroding polylactide-polyglycolide implants of
      differing crystallinity in rabbit tibial bone chambers.
AB  - Eroding poly(DL-lactide-co-glycolide) (PDLLG) washers and poly(L-lactide-co
      glycolide) (PLLG) threads were observed chronically in vivo following loading in
      a bone chamber tibial implant (BCI). Images were recorded using intravital
      microscopy of the implanted rabbit. Erosion and bone healing, as represented by
      angiogenesis and osteogenesis, was determined from changes in projected area of
      observed polymer, vessels and bone, respectively. Erosion rates of the two
      polymers were significantly different. Healing adjacent to both polymers differed
      significantly from controls. Healing response to each polymer was also different,
      with the faster eroding PDLLG causing more deviation from normal osteogenesis and
      angiogenesis than did PLLG. It was speculated that the faster eroding polymer
      released macrophage-stimulating fragments earlier in the healing process, thus
      altering the normal macrophage-endothelial cell interaction which in turn
      affected angiogenesis-linked components of osteogenesis.

PMID- 9195332
TI  - Biospecific polymers: recognition of phosphorylated polystyrene derivatives by
      anti-DNA antibodies.
AB  - The recognition of DNA-like phosphorylated polymers by anti-DNA antibodies from
      the plasma of systemic lupus erythematosus patients was evidenced a few years ago
      by our research group. However, the radioimmunological Farr assay used for the
      assessment of anti-DNA antibodies adsorption was not sensitive enough to give
      accurate results, particularly in the case of weak levels of antibodies. An
      alternative method based on the use of radiolabelled species was set up in order
      to check the validity of previous results. Polystyrene resins with different
      levels in phosphate groups substitution were assessed with regard to their
      interactions with anti-DNA antibodies. Results show that the anti-DNA antibodies
      affinity is dependent on the composition of the polymers and reaches a maximum
      for a composition of 17.5-22.5 mol of phosphorus per 100 mol of monomeric units.
      This composition corresponds to the DNA-like polymer previously described. A
      computer-assisted method was used in order to have an insight into the structure
      of the active sites responsible for the DNA-like behaviour of this polymer.
      Numerical simulations of the phosphorylation reaction were performed using a
      Monte Carlo method, taking the structure predictions and the environment of the
      phosphorylated units into account. A number of thus generated virtual polymers
      correlated with the experimental results of the adsorption of anti-DNA
      antibodies. The chemical structure of the active site was determined by
      computations introducing selected hypotheses on the structure of the
      phosphorylated units. Moreover, since the number of active sites is directly
      related to the number of adsorbed anti-DNA antibodies in the experimental
      results, the most probable structure of the active sites is proposed and compared
      to a fragment of DNA. Conclusions are that the distances between the phosphate
      groups in the active sites of the DNA-like polymer and in the DNA fragment are
      similar. Optimal conditions for the purification of SLE sera by highly specific
      liquid chromatography using phosphorylated polystyrene resins of precise
      compositions as stationary phases can thus be envisaged, as well as a new method
      for the detection of anti-DNA antibodies.

PMID- 9195334
TI  - Embolic materials for endovascular treatment of cerebral lesions.
AB  - Recently developed soft microcatheters can be maneuvered endovascularly into the
      brain, permitting treatment of lesions without conventional neurosurgery.
      Progress in biomaterial science has contributed significantly to the development
      of this new therapeutic modality termed intravascular neurosurgery or
      interventional neuroradiology. Although embolic materials play an important role,
      ideal materials have yet to be devised. Various embolic materials in clinical use
      are reviewed, such as cyanoacrylates, ethylene-vinyl alcohol copolymer mixtures,
      Ethibloc, ethanol, estrogen, poly(vinyl acetate), cellulose acetate polymer,
      poly(vinyl alcohol), gelatin sponges, microfibrillar collagen, surgical silk
      sutures, detachable balloons, and coils. The materials are reviewed in the
      context of treatment application for various brain lesions, such as arteriovenous
      malformations, cerebral aneurysms, and head and neck tumors. Further developments
      in biomaterial polymer science can bring about progress against brain diseases.

PMID- 9195333
TI  - The mechanism of anticoagulant activity of a novel heparinoid sulfated glucoside
      bearing polymer.
AB  - In our previous study on glycoside polymer, it was discovered that sulfated
      poly(glucosyloxyethyl methacrylate) [poly(GEMA)-sulfate], which bears sulfated D
      (+)-glucose, exhibited anticoagulant activity. The anticoagulant activity of
      poly(GEMA)-sulfate in solution was prolonged by increasing the dose or degree of
      sulfation of the polymer. In this study, to recognize the mechanism of
      anticoagulant activity of poly(GEMA)-sulfate, we estimated the binding capacity
      of antithrombin III to thrombin and some in vitro clotting tests in the presence
      of poly(GEMA)-sulfate. These results revealed that poly(GEMA)-sulfate had an
      anticoagulant mechanism which differed to that of heparin. We concluded that the
      anticoagulant activity of poly(GEMA)-sulfate is responsible for inhibiting fibrin
      network formation by the insoluble ion complex between fibrinogen and poly(GEMA)
      sulfate.

PMID- 9195335
TI  - Ab initio quantum mechanics analysis of imidazole C-H...O water hydrogen bonding
      and a molecular mechanics forcefield correction.
AB  - While it is well established that classical hydrogen bonds play an important role
      in enzyme structure, function and dynamics, the role of weaker, but 'activated' C
      H donor hydrogen bonds is poorly understood. The most important such case
      involves histidine which often plays a direct role in enzyme catalysis and
      possesses the most acidic C-H donor group of the standard amino acids. In the
      present study, we obtained optimized geometries and hydrogen bond interaction
      energies for C-H...O hydrogen bonded complexes between methane, ethylene,
      benzene, acetylene, and imidazole with water at the MP2-FC/6-31++G(2d,2p) and MP2
      FC/aug-cc-pVDZ/MP2-FC/6-31++G(2d,2p) levels of theory. A strong linear
      relationship is obtained between the stability of the various hydrogen bonded
      complexes and both separation distances for H...O and C----O. In general, these
      calculations indicate that C-H...O interactions can be classified as hydrogen
      bonding interactions, albeit significantly weaker than the classical hydrogen
      bonds, but significantly stronger than just van der Waals interactions. For
      instance, while the electronic energy of stabilization at the MP2-FC/aug-cc
      pVDZ/MP2-FC/6-31++G(2d,2p) level of theory of a water O-H...O water hydrogen bond
      is 4.36 kcal/mol more stable than the methane C-H...O water interaction, the
      water-water hydrogen bond is only 2.06 kcal/mol more stable than the imidazole Ce
      H...O water hydrogen bond. Neglecting this latter hydrogen bonding interaction is
      obviously unacceptable. We next compare the potential energy surfaces for the
      imidazole Ce-H...O water and imidazole Na-H...O hydrogen bonded complexes
      computed at the MP2/6-31++G(2d,2p) level of theory with the potential energy
      surface computed using the AMBER molecular mechanics program and forcefields.
      While the Weiner et al and Cornell et al AMBER forcefields reasonably account for
      the imidazole N-H...O water interaction, these forcefields do not adequately
      account for the imidazole Ce-H...O water hydrogen bond. A forcefield modification
      is offered that results in excellent agreement between the ab initio and
      molecular mechanics geometry and energy for this C-H...O hydrogen bonded complex.

PMID- 9195337
TI  - Human nucleotide excision repair protein XPA: 1H NMR and CD solution studies of a
      synthetic peptide fragment corresponding to the zinc-binding domain (101-141).
AB  - A peptide corresponding to residues 101-141 of the human nucleotide excision
      repair protein XPA was synthesized with an isoleucine substituted for L138 and
      its solution structure studied by circular dichroism and homonuclear 1H NMR
      spectroscopy. The peptide, (XPA-41), contains a C4-type zinc-binding motif, C105
      (X)2-C108-(X)17-C126-(X)2-C129, which XPA requires for damaged-DNA binding
      activity. The proton resonances of XPA-41 without zinc (apoXPA-41) were assigned
      using homonuclear TOCSY, NOESY and DQF-COSY data and show the apo-zinc peptide is
      a random coil. The peptide was folded with the addition of 1.2 equivalents of
      ZnCl2 in dilute solution at pH 4.0. Electrospray ionization mass spectroscopy
      illustrated an increase in the molecular weight of XPA-41 by 65 amu. Circular
      dichroism spectra of the zinc-folded peptide (zXPA-41) showed the acquisition of
      elements of secondary structure. Such a conclusion was confirmed with 1H NMR data
      collected at 25 degrees C, pH 6.3. H alpha-secondary shifts and NOE patterns
      indicate that regions V102-C105 and G109-F112 form an anti-parallel beta-sheet
      and residues N128-K137 form a nascent alpha-helix. Rapid exchange of most amide
      resonances between S115-C126 prohibited unambiguous assignment of all the proton
      resonances in this region. However, a 1.19 ppm downfield shift of the H alpha
      resonance of T125 relative to the apo-zinc peptide, together with downfield
      shifted H alpha resonances for the adjacent residues (P124 and L123), suggest a
      second beta-sheet is present in the S115-C126 region. On the basis of structural
      similarities to GATA-1 (Science 261:438-446), a homology generated structure for
      zXPA-41 was made, using GATA-1 as the template, which satisfied all the observed
      NOEs. Using the hybrid homology-NMR based zXPA-41 structure and analogy to GATA
      1, models for the role played by the zinc-binding core (101-141) of XPA in DNA
      damage recognition are proposed.

PMID- 9195336
TI  - Homology modeling of adenylosuccinate synthetase from Saccharomyces cerevisiae
      reveals a possible binding region for single-stranded ARS sequences.
AB  - Adenylosuccinate synthetase from Saccharomyces cerevisiae was investigated in
      order to find a structural explanation for its ability to bind specifically to
      single-stranded ARS elements (autonomously replicating sequences). Using the E.
      coli enzyme as template, a model for the structure of adenylosuccinate synthetase
      from S. cerevisiae was generated and subsequently refined by molecular dynamics
      techniques. The resulting three-dimensional structure offers an explanation for
      the DNA binding activity of the yeast enzyme by revealing a distinct basic region
      that is not present in the homologous enzymes from other organisms. The model is
      also in good agreement with biochemical data available for a mutant protein in
      which Glycine 252 is replaced by Aspartate. On the basis of the model a
      significant structural distortion near the catalytic center was predicted for
      this mutant, corresponding well to the enzymatic inactivity observed. The mutant
      enzyme shows larger structural fluctuations than the wild-type protein according
      to the results of two independent molecular dynamics simulations.

PMID- 9195338
TI  - Influence of drug binding on DNA flexibility: a normal mode analysis.
AB  - DNA-drug complexes are important because of their pharmacological interest but,
      in addition, they provide a useful model to study the essential aspects of DNA
      recognition processes. In order to investigate the influence of ligand binding on
      the dynamic properties of DNA we have carried out normal mode analysis for
      complexes with drugs of two types: a typical intercalator, 9-aminoacridine, and a
      typical groove binder, netropsin. Normal modes are analysed in terms of
      helicoidal parameter variations with special attention being paid to global
      deformations of the double helix. The results show that the influence of these
      two drugs is very different. Intercalation of 9-aminoacridine leads to an
      increase in the flexibility of the intercalated dinucleotide step, with notably
      larger vibrational amplitudes for both roll and twist parameters compared to free
      DNA. In contrast, the groove binding of netropsin induces a stiffening of the DNA
      segment which is in contact with the drug reflected by decreased vibrational
      amplitudes for backbone angles and inter base pair helicoidal parameters and an
      increase in vibrations for adjacent base pairs in terms of buckle and propeller
      twist.

PMID- 9195339
TI  - Distortions of the DNA double helix induced by 1,3-trans
      diamminedichloroplatinum(II)-intrastrand cross-link: an internal coordinate
      molecular modeling study.
AB  - A trans-diamminedichloroplatinum(II) (trans-DDP) intrastrand adduct within the
      sequence d(TCTG*TG*TC).d(GACACAGA) (where G* represents a platinated guanine) is
      modeled on the basis of qualitative experimental data concerning global unwinding
      and curvature as well as information on base pairing. Modeling is performed using
      the internal coordinate JUMNA program, specific to nucleic acids, and modified to
      include the possibility of covalently bound ligands. Calibration of the energy
      functions representing the Pt-N7 bond with guanine is described. The platinum
      atom and the platinum-nitrogen bonds are parameterized for use in the Huckel Del
      Re method to calculate monopoles at each atom. These monopoles are consistent
      with the Flex force field included in Jumna. By developing an appropriate
      minimization protocol we are able to generate stable, distorted three-dimensional
      structures compatible with the experimental data and including an unusually high
      global unwinding. No a priori geometric assumptions are made in generating these
      structures.

PMID- 9195340
TI  - Single-stranded DNA and RNA targeted triplex-formation: UV, CD and molecular
      modeling studies of foldback triplexes containing different RNA, 2'-OMe-RNA and
      DNA strand combinations.
AB  - We studied the influence of different 2'-OMe-RNA and DNA strand combinations on
      single strand targeted foldback triplex formation in the Py.Pu:Py motif using
      ultraviolet (UV) and circular dichroism (CD) spectroscopy, and molecular
      modeling. The study of eight combinations of triplexes (D.D:D, R*.D:D, D.D:R*,
      R*.D:R*, D.R:D, R*.R:D, D.R:R*, and R*.R:R*; where the first, middle, and last
      letters stand for the Hoogsteen Pyrimidine, Watson-Crick [WC] purine and WC
      pyrimidine strands, respectively, and D, R and R* stand for DNA, RNA and 2'-OMe
      RNA strands, respectively) indicate more stable foldback triplex formation with a
      DNA purine strand than with an RNA purine strand. Of the four possible WC
      duplexes with RNA/DNA combinations, the duplex with a DNA purine strand and a 2'
      O-Me-RNA pyrimidine strand forms the most thermally stable triplex, although its
      thermal stability is the lowest of all four duplexes. Irrespective of the duplex
      combination, a 2'-OMe-RNA Hoogsteen pyrimidine strand forms a stable foldback
      triplex over a DNA Hoogsteen pyrimidine strand confirming the earlier reports
      with conventional and circular triplexes. The CD studies suggest a B-type
      conformation for an all DNA homo-foldback triplex (D.D:D), while hetero-foldback
      triplex spectra suggest intermediate conformation to both A-type and B-type
      structures. A novel molecular modeling study has been carried out to understand
      the stereochemical feasibility of all the combinations of foldback triplexes
      using a geometric approach. The new approach allows use of different combinations
      of chain geometries depending on the nature of the chain (RNA vs. DNA).

PMID- 9195341
TI  - Prediction of sequentially optimal RNA secondary structures.
AB  - A rigorous mathematical modeling of the RNA sequential folding process during
      transcription is proposed. It is based, at each transcription step, on a
      homogeneous markovian jump process, the state space of which is the set of
      structures constructible on the part of the RNA already transcribed. A
      theoretical formula permitting the computation of the structures probabilities at
      the end of the RNA transcription is derived. Successive approximations, aimed at
      reducing the size of the state space, permit the design of a prediction
      algorithm. The algorithm is tested on some structural RNAs (tRNA, 5S, 16S,
      hammerhead, ...), results are discussed and possible improvements are proposed.

PMID- 9195342
TI  - Nucleosomes as topological rheostats.
AB  - Induction of transcription in eukaryotic promoters is accompanied by removal or
      remodeling of nucleosomes. Given that this process causes release of torsional
      stress, the question is asked relative to its fate and to its effects on local
      DNA conformation. Is it dispersed by free rotation through surrounding
      nucleosomes or does it stay locally to be used in the modulation or activation of
      the transcription machinery? The results of the calculations relative to the
      onset of writhing suggest that the free energy made available by removal of
      nucleosomes is in the range of values that corresponds to the transition linking
      difference, thus pointing to a possible regulatory mechanism for the local use of
      free energy in promoters.

PMID- 9195343
TI  - Construction of double-helical DNA structures based on dinucleotide building
      blocks.
AB  - We present a new method for building full 3-D structures of DNA sequences. A
      database of the conformational properties of dinucleotide steps has been compiled
      using X-ray crystal structures of oligonucleotides. The protocol uses these
      dinucleotides as building blocks to generate three dimensional structures of any
      required sequence in any required conformation.

PMID- 9195344
TI  - Conformational properties of the TATA-box binding sequence of DNA.
AB  - Nanosecond scale molecular dynamics simulations in water demonstrate that the DNA
      oligomer, GCGTATATAAAACGC, which contains a target site for the TATA-box binding
      protein (TBP), has an intrinsic preference to adopt an A-like conformation in the
      region of the TATA-box and undergoes bending related to that seen within in the
      TBP complex. This result is obtained from two independent simulations using
      different starting structures. In line with earlier suggestions of Guzikevich
      Guerstein and Shakked, these simulations imply that an A-DNA conformation may be
      an important intermediate step in forming the strongly distorted DNA observed
      within the crystallographically determined complex with TBP. These results also
      support modeling studies by Lebrun et al. which suggest that the TBP binding
      mechanism can be broken down into a backbone transition to an A-like form coupled
      with a mechanical distortion which locally stretches and unwinds the DNA.

PMID- 9195345
TI  - Hemodynamic changes during laparoscopic cholecystectomy in patients with severe
      cardiac disease.
AB  - STUDY OBJECTIVE: To evaluate the hemodynamic changes and need for pharmacologic
      interventions during laparoscopic cholecystectomy in patients with severe cardiac
      dysfunction. DESIGN: Prospective open study. SETTING: University hospital.
      PATIENTS: 17 ASA physical status III and IV patients with severe cardiac
      dysfunction undergoing elective laparoscopic cholecystectomy. INTERVENTIONS: A
      standardized general anesthetic and surgical technique was used for all patients.
      In addition to routine monitoring, invasive hemodynamic monitoring included
      radial and pulmonary artery (PA) cannulation. MEASUREMENTS AND MAIN RESULTS:
      Hemodynamic parameters were recorded prior to induction of anesthesia, 5 minutes
      after induction of anesthesia but prior to incision, 5 minutes after carbon
      dioxide (CO2) insufflation and head-up tilt, every 10 minutes after change of
      position, after deflation of the abdomen and return to supine position, and 10
      minutes after attaining supine position. Need for any pharmacologic interventions
      [to maintain mean arterial pressure (MAP) < 100 mmHg and/or systemic vascular
      resistance (SVR) < 2,000 dynes sec/cm-5, and/or cardiac index (CI) > 1.5
      L/min/m2] and the incidence of any myocardial morbidity and mortality was noted.
      CI decreased significantly (p < 0.05) following insufflation and remained low
      until exsufflation. MAP, SVR, and PA occlusion pressure increased significantly
      (p < 0.05) after CO2 insufflation. Three of the 17 patients required
      administration of nitroglycerin to maintain the MAP and SVR within the accepted
      limits, one of whom also required administration of dobutamine to maintain CI.
      There was no myocardial morbidity or mortality in the perioperative period.
      CONCLUSION: Laparoscopic cholecystectomy in patients with severe cardiac
      dysfunction results in significant hemodynamic changes.

PMID- 9195346
TI  - How controversial are anesthetic controversies?
AB  - STUDY OBJECTIVES: To determine how controversial the management of a number of
      clinical scenarios that are labeled as controversial (eg, how to induce
      anesthesia in the "open eye-full stomach" patient) are among those practicing
      anesthesia. DESIGN: Written survey. SETTING: A national anesthesiology review
      course. SUBJECTS: 575 anesthesiologists attending the review course.
      INTERVENTIONS: Anesthesiologists were presented 11 scenarios regarding some
      specific controversies in anesthetic management; each scenario also described a
      suggested course of management. Two questions were asked for each scenario: "Is
      this acceptable practice?" and "Would you do this in your own practice?" The
      scenarios included using succinylcholine for an "open eye-full stomach" patient,
      not evaluating preoperatively the cardiac status of a patient after receiving
      adriamycin therapy, using triggering drugs after a negative muscle biopsy for
      malignant hyperthermia, ordering a pregnancy test preoperatively for all females
      of child-bearing age, and seven others. MEASUREMENTS AND MAIN RESULTS: For each
      scenario, comparisons between the number of respondents who felt a particular
      management was acceptable practice and the number who would do this in their own
      practice were made using chi-square analysis; p < or = 0.05 was considered
      significant. 160 (27.8%) surveys were returned. In ten scenarios, there was 70%
      or less agreement about whether a technique was acceptable. In six scenarios,
      there was a significant difference between the number of respondents who felt a
      suggested management was acceptable practice and the number who would use it in
      their own practice. CONCLUSIONS: This survey of anesthesiologists regarding these
      controversial clinical scenarios showed that (a) most scenarios were in fact
      controversial amongst those in practice, and (b) there were disparities between
      whether a technique is believed to be acceptable practice and whether it would be
      used in one's own practice.

PMID- 9195347
TI  - Is intravenous lidocaine an effective adjuvant for endotracheal intubation in
      children undergoing induction of anesthesia with halothane-nitrous oxide?
AB  - STUDY OBJECTIVE: To evaluate the efficacy of intravenous (i.v.) lidocaine in
      suppressing the cough reflex and increases in intraocular pressure (IOP), heart
      rate (HR), and mean arterial pressure (MAP) elicited by endotracheal intubation.
      DESIGN: Prospective, randomized, placebo-controlled, blinded study. PATIENTS: 60
      ASA physical status 1 premedicated children aged 2 to 6 years undergoing
      induction of anesthesia with halothane-nitrous oxide (N2O) for surgery to correct
      strabismus. INTERVENTIONS: Patients were randomly divided into two groups of 30
      each. The control group (C) received saline and the treatment group (L) received
      2 mg/kg i.v. lidocaine 90 seconds prior to endotracheal intubation. MEASUREMENTS
      AND MAIN RESULTS: Awake HR and MAP; IOP, HR, and MAP 45 seconds prior to
      endotracheal intubation, immediately after endotracheal intubation, and 1 minute
      later, were recorded. Coughing was noted at endotracheal intubation. Lidocaine
      prevented coughing and a significant increase in IOP. Although significant
      increases in HR and MAP were observed in both groups (comparing preintubation and
      postintubation values), these increases were significantly less in the L group
      compared with the C group. CONCLUSIONS: In healthy premedicated children, aged 2
      to 6 years, who are undergoing induction of anesthesia with halothane-N2O, 2
      mg/kg of lidocaine given 90 seconds prior to laryngoscopy effectively suppresses
      the cough reflex and increase in IOP secondary to endotracheal intubation and
      attenuates increases in HR and MAP.

PMID- 9195348
TI  - Lightwand intubation of infants and children.
AB  - STUDY OBJECTIVE: To examine factors contributing to successful lightwand (lighted
      stylet) intubation of infants and children. DESIGN: Prospective observational
      study. SETTING: University hospital. PATIENTS: 125 children under age 10 years
      presenting for elective surgery. INTERVENTIONS: Prototype lightwands specifically
      designed for pediatric patients were used. Intubations were done by anesthesia
      residents with little or no prior lightwand experience. All attempts were
      recorded on videotape. In a subgroup of 14 patients, an endoscopic view of the
      lightwand was also recorded with a flexible nasopharyngoscope. MEASUREMENTS AND
      MAIN RESULTS: 125 patients with a mean age of 3.0 years (+/- 2.4 years SD; range:
      3 weeks to 9 years) were enrolled. 83.2% were intubated using the lightwand,
      including 75.5% (34 of 45) of infants weighing less than 10 kg. Of the 21 failed
      intubations, 8 were due to an inappropriately large endotracheal tube, as
      recognized during direct laryngoscopy; 4 were due to other reasons discussed; and
      9 (persistent vallecular or esophageal entry) could not be explained from
      videotape analysis. Factors contributing to successful intubation included: (1)
      use of a shoulder roll and slight head extension; (2) conscientious alignment of
      airway axes; (3) anterior jaw lift to elevate the epiglottis; and (4) gentle
      handling of the lightwand to avoid displacing soft tissue. Inability to advance
      the lightwand despite correct glow is caused by entrapment in the vallecula, hang
      up of the lightwand on the aryepiglottic folds, subglottic narrowing, or vocal
      cord closure. CONCLUSIONS: Lightwand intubation in children uses both tactile and
      visual cues regarding the location of the endotracheal tube tip. Attention to
      detail results in a high level of success among novice users of the pediatric
      lightwand. Endoscopic and external videotaping gave us a means of monitoring the
      progress of mechanical skills among novice users.

PMID- 9195349
TI  - Intrathecal morphine for postoperative analgesia following repair of frontal
      encephaloceles in children: comparison with intermittent, on-demand dosing of
      nalbuphine.
AB  - STUDY OBJECTIVE: To determine the efficacy of lumbar intrathecal (i.t.) morphine
      in a dose of 0.02 mg/kg in providing analgesia following repair of frontal
      encephaloceles. DESIGN: Prospective, open-label investigation of i.t. morphine
      with secondary comparison to a retrospective cohort. SETTING: Metropolitan
      hospital in the Philippines. PATIENTS: 24 ASA physical status I and II children
      undergoing frontal encephalocele repair. INTERVENTIONS: Following induction of
      general anesthesia. I.t. morphine (Group 1) was administered via single-shot
      technique or through a lumbar i.t. drain placed for cerebrospinal fluid drainage
      during the surgical procedure. Postoperative analgesia was assessed by visual
      analog score in patients greater than 5 years of age or a behavioral score in
      patients less than 5 years of age. The retrospective cohort received
      postoperative analgesia with intermittent doses of intravenous nalbuphine (Group
      2). MEASUREMENTS AND MAIN RESULTS: Group 1 had decreased postoperative analgesic
      requirements, decreased intraoperative inhalational anesthetic requirements, and
      a longer time to the first request for postoperative analgesia than Group 2. The
      time to the first request for postoperative analgesia was 16.0 +/- 9.1 hours in
      Group 1 and 1.6 +/- 1.2 hours in Group 2 (p < 0.0001). Six of 12 patients in
      Group 1 required no analgesic drugs during the first 24 postoperative hours while
      all 12 patients in Group 2 (p = 0.02) did require analgesic drugs during this
      period. The patients in Group 1 who did not require supplemental analgesic drugs
      maintained pain scores of 2 or less throughout the first 24 postoperative hours.
      CONCLUSION: Lumbar IT morphine provides effective analgesia following repair of
      frontal encephaloceles in children and adolescents.

PMID- 9195350
TI  - Efficacy and safety of single injection peribulbar block performed by
      anesthesiologists prior to cataract surgery.
AB  - STUDY OBJECTIVE: To evaluate the safety and efficacy of single inferior injection
      peribulbar block administered by anesthesiologists prior to cataract surgery.
      DESIGN: Retrospective chart review. SETTING: Freestanding surgery center
      (teaching). PATIENTS: 1,074 consecutive patients who were treated over a two-year
      period. INTERVENTIONS: Single inferior injection peribulbar block and one
      inferior peribulbar supplement when indicated. MEASUREMENTS AND MAIN RESULTS: The
      efficacy of a single inferior injection peribulbar block was 74%; 96% with one
      inferior peribulbar injection supplement. There were no ocular or systemic
      complications. CONCLUSION: Single inferior injection peribulbar block is safe and
      effective when administered by anesthesiologists.

PMID- 9195351
TI  - Propofol decreases ocular pressure in outpatients undergoing trabeculectomy.
AB  - STUDY OBJECTIVE: To examine the effect of a continuous low-dose intravenous
      (i.v.) infusion of propofol on ocular pressure in outpatients undergoing
      trabeculectomy. DESIGN: Randomized, prospective study. SETTING: Teaching
      hospital. PATIENTS: 40 unpremedicated outpatients with history of primary open
      angle glaucoma undergoing trabeculectomy. INTERVENTIONS: In the operating room,
      an infusion of 5% dextrose into a peripheral vein was started. The propofol group
      (n = 20) received 0.5 mg/kg i.v. propofol bolus followed immediately by a
      continuous 0.5 mg/kg/hr infusion. The control group (n = 20) received only the
      dextrose solution. A peribulbar block was performed with bupivacaine with added
      adrenaline, plus lidocaine. The ocular pressure (tonometer) on the eye undergoing
      trabeculectomy and the other eye, blood pressure (BP), and heart rate (HR) were
      measured at the following times: (1) preoperatively; (2) 2 minutes; (3) 5
      minutes; (4) 10 minutes; (5) 15 minutes after propofol bolus administration for
      the propofol group (approximately 4 minutes after the peribulbar blockade on the
      eye undergoing surgery for the propofol and control groups). MEASUREMENTS AND
      MAIN RESULTS: Ocular pressure decreased 2 minutes after propofol infusion (p <
      0.0001) and remained significantly lower than in the control group throughout the
      study period. All patients remained awake and cooperative during all procedures.
      Mean BP and HR were kept constant throughout the study. CONCLUSION: Low-dose
      propofol sedation resulted in a decrease in ocular pressure, was quick in onset,
      and was unrelated to BP and HR. The decrease in ocular pressure may be due to
      relaxation of extraocular muscles by propofol.

PMID- 9195352
TI  - Elevated plasma levels of interleukin-6, interleukin-8, and granulocyte colony
      stimulating factor during and after major abdominal surgery.
AB  - STUDY OBJECTIVE: To evaluate the influence of major abdominal surgery on the
      plasma levels of inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL
      8) and granulocyte colony-stimulating factor (G-CSF). DESIGN: Prospective study.
      SETTING: University hospital. PATIENTS: 10 ASA physical status I and II patients
      undergoing upper abdominal surgery. INTERVENTIONS: All patients received combined
      general-epidural anesthesia with isoflurane and nitrous oxide, after insertion of
      an epidural catheter at T7-T9 dosed with 1.5% lidocaine. MEASUREMENTS AND MAIN
      RESULTS: Plasma cytokine (IL-6, IL-8, G-CSF) levels were determined with an
      enzyme-linked immunosorbent assay (ELISA) at pre-anesthesia, 0, 2, and 4 hours
      during surgery, and at the end of surgery, followed by sampling on the morning of
      postoperative days 1 (POD1) and 3 (POD3). Plasma cortisol levels were also
      determined. The plasma levels of IL-6 increased gradually after skin incision and
      reached the maximal value at the end of surgery (p < 0.001). IL-8 levels also
      increased from the baseline value to their maximum at the end of surgery (p <
      0.05). G-CSF levels were elevated from the pre-anesthesia value to their maximum
      by the end of operation (p < 0.005). Plasma cortisol levels were increased after
      skin incision (p < 0.001). Postoperative cytokine levels correlated significantly
      with each other (r = 0.68, p < 0.05 for IL-6 vs. IL-8; r = 0.81, p < 0.005 for IL
      6 vs. G-CSF; and r = 0.84, p < 0.005 for IL-8 vs. G-CSF). Postoperative IL-6
      levels and intraoperative blood loss correlated significantly (r = 0.64, p <
      0.05). CONCLUSIONS: These results suggest that major upper abdominal surgery
      stimulates the release of inflammatory cytokines presumably from the operation
      site. Further study is warranted to evaluate the modulation of inflammatory
      responses in the perioperative period.

PMID- 9195353
TI  - Efficacy and financial benefit of an anesthesiologist-directed university
      preadmission evaluation center.
AB  - STUDY OBJECTIVE: To study the effectiveness of an anesthesiologist-directed
      preadmission evaluation center (PEC) in our institution. DESIGN: I: Preoperative
      test costs were measured on two sets of patients undergoing same-day surgery. II:
      Rate of cancellation was measured on all patients undergoing same-day surgery in
      a subsequent one-year time period. SETTING: The PEC, short procedure unit, and
      same-day admission unit of a university hospital. PATIENTS: I: 3,062 male and
      female patients undergoing same-day surgery between January 1, 1992, and August
      31, 1992. II: 9,454 male and female patients undergoing same-day surgery between
      July 1, 1993, and June 30, 1994. INTERVENTIONS: Age, ASA physical status, type of
      surgery performed, and tests ordered were recorded in two groups of same-day
      surgical patients. Group S had testing primarily ordered by surgeons, augmented
      by the anesthesiologists in the PEC. Group A had testing primarily ordered by the
      anesthesiologists in the PEC, but surgeons could still order tests they felt
      necessary. On the day of surgery, the attending anesthesiologist recorded any
      additional testing that was required or would have altered intraoperative
      management. In a follow-up study, cancellations of same-day surgical patients
      were recorded for a one-year period. MEASUREMENTS AND MAIN RESULTS: I: With the
      exception of complete blood counts with differentials, significantly fewer tests
      were ordered in Group A than Group S. These changes produced an average cost
      savings of $20.89 per patient. There were no recorded cancellations or apparent
      alterations in intraoperative management attributable to inadequate testing. II:
      Of the 9,454 same-day procedures from 7/1/93 to 6/31/94, 66 were cancelled on the
      day of the procedure. None of the patients seen in the PEC were cancelled due to
      causes possibly preventable by a PEC, unlike the cases of 4 patients who had not
      been evaluated in teh PEC and were cancelled. CONCLUSION: A PEC, in which the
      anesthesiologist primarily orders preoperative tests and approves patients'
      readiness for surgery, is both an efficient and cost-effective system.

PMID- 9195355
TI  - Continuous jugular venous versus nasopharyngeal temperature monitoring during
      hypothermic cardiopulmonary bypass for cardiac surgery.
AB  - STUDY OBJECTIVE: To compare jugular venous to nasopharyngeal temperature during
      hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective observational
      study. SETTING: Tertiary care teaching hospital. PATIENTS: 5 ASA physical status
      IV patients (40 to 65 years of age) having cardiac surgery with hypothermic CPB.
      INTERVENTIONS, MEASUREMENTS AND MAIN RESULTS: Jugular venous and nasopharyngeal
      temperatures were recorded throughout the procedure with comparisons made during
      four time periods: pre-CPB, during CPB, during rewarming, and post-CPB. The
      patients underwent 85.8 +/- 45.8 minutes (mean +/- SD) of hypothermic CPB,
      cooling to 26.3 +/- 7.6 degrees C (nasopharyngeal) followed by rewarming at 0.35
      +/- 0.1 degree C (nasopharyngeal)/min. There was a high degree of precision
      between the two temperature sites, but marked differences in bias. In particular,
      temperature bias was more pronounced during rewarming from CPB compared with
      other time periods (p < 0.05) where jugular venous temperature was greater than
      nasopharyngeal temperature by 3.4 degrees C. CONCLUSION: Nasopharyngeal
      temperature underestimates jugular venous temperature during rewarming from
      hypothermic CPB. As a result, the brain may be exposed to periods of
      hyperthermia, possibly increasing the risk of neurologic injury associated with
      CPB.

PMID- 9195354
TI  - Ritanserin attenuates the in vitro effects of the 5-HT2 receptor agonist DOI on
      skeletal muscles from malignant hyperthermia-susceptible patients.
AB  - STUDY OBJECTIVES: To study the in vitro effects of the serotonin2 (5-HT2)
      receptor agonist 1-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in skeletal
      muscle specimens from malignant hyperthermia-susceptible (MHS) and normal (MHN)
      patients following pretreatment with the 5-HT2 receptor antagonist ritanserin.
      DESIGN: Prospective study. SETTING: Malignant hyperthermia (MH) laboratory at a
      university hospital. PATIENTS: 41 patients undergoing in vitro contracture test
      for diagnosis of MH susceptibility. INTERVENTIONS: Skeletal muscle biopsies in
      adult patients were performed with a 3-in-1 nerve block with 40 ml prilocaine 1%.
      In children, general anesthesia was induced with 50 micrograms/kg alfentanil
      intravenously (i.v.) and 2 to 2.5 micrograms/kg propofol i.v. and maintained with
      a continuous infusion of propofol (< or = 150 micrograms/kg/min) and nitrous
      oxide (66%) in oxygen. MEASUREMENTS AND MAIN RESULTS: Patients were first
      classified as MHS or MHN by the in vitro contracture test according to the
      European MH protocol. Surplus muscle specimens of 21 MHS and 20 MHN patients were
      used in this study. At first, DOI was added to the organ bath at a concentration
      of 0.02 mM. In the second part of the study, muscle specimens were preincubated
      with ritanserin 0.01 mM for 10 minutes before DOI 0.02 mM was added to the bath.
      Muscle specimens from all patients developed contractures after administration of
      DOI. The onset of contractures was significantly faster in MHS muscles, and the
      magnitude of contracture was significantly greater than in MHN. The muscle twitch
      decreased significantly in both groups after DOI. After pretreatment with
      ritanserin, start of contracture was significantly delayed in MHS muscles. MHN
      muscles failed to develop contractures. The maximum level of contracture was
      significantly reduced in MHS. Muscle twitch decreased also in both MHS and MHN
      groups. CONCLUSIONS: The findings may indicate that stimulation of 5-HT2
      receptors is involved in MH induction. Furthermore, 5-HT2 receptor antagonists
      could possibly be effective in preventing MH. Additional studies are required to
      determine if administration of 5-HT2 receptor antagonists could be of additional
      value in the treatment or prevention of anesthetic-induced MH.

PMID- 9195356
TI  - Rocuronium versus succinylcholine for rapid-sequence induction using a variation
      of the timing principle.
AB  - STUDY OBJECTIVE: To determine if, using a variation of the "timing" principle,
      0.6 mg/kg of rocuronium can achieve an onset time and intubating conditions
      similar to those achieved with succinylcholine. STUDY DESIGN: Prospective,
      randomized, double-blind clinical comparison. SETTING: Operating room in a
      university medical center. PATIENTS: 42 ASA physical status I and II patients
      undergoing general anesthesia for elective surgery. INTERVENTIONS: All patients
      were fitted with a Grass FT-10 force transducer attached to the thumb.
      Supramaximal stimulation was applied to the ulnar nerve with a variable current
      peripheral nerve stimulator. 22 patients (succinylcholine group) received a
      placebo bolus injection followed 20 seconds later by thiopental 4 to 5 mg/kg and
      succinylcholine 1 mg/kg; 20 additional patients (rocuronium group) received a
      bolus dose of rocuronium 0.6 mg/kg followed 20 seconds later by thiopental 4 to 5
      mg/kg and a placebo bolus injection. MEASUREMENTS AND MAIN RESULTS: We measured
      the onset time from administration of the muscle relaxant to 95% twitch reduction
      and assessed the quality of intubating conditions 60 seconds after the induction
      of anesthesia. There was a significant difference in the mean onset time of
      rocuronium (72 sec) versus succinylcholine (42 sec, p < 0.0001). However, there
      was no significant difference in intubating conditions 60 seconds after
      administration of thiopental. CONCLUSION: Rocuronium given 20 seconds prior to
      thiopental provides intubating conditions equivalent to thiopental
      succinylcholine for rapid-sequence inductions, circumventing rocuronium's longer
      onset time to 95% neuromuscular blockade.

PMID- 9195357
TI  - Catecholamine and renin-angiotensin response during controlled hypotension
      induced by prostaglandin E1 combined with hemodilution during isoflurane
      anesthesia.
AB  - STUDY OBJECTIVE: To evaluate the catecholamine and renin-angiotensin response
      during controlled hypotension combined with hemodilution in the clinical setting.
      DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Nagasaki
      Rosai Hospital. PATIENTS: 30 ASA physical status I and II female patients
      scheduled for total hip arthroplasty. INTERVENTIONS: Patients were randomly
      divided into three groups. Group A (N = 10) received hemodilution alone. Group B
      (N = 10) received controlled hypotension alone. Group C (N = 10) received
      hemodilution plus controlled hypotension. Hemodilution was carried out after
      induction of anesthesia, in which drawn blood was replaced with 6% hydroxyethyl
      starch, and the final hematocrit value was approximately 22%. Controlled
      hypotension was induced with prostaglandin E1 (PGE1) to maintain mean arterial
      blood pressure at 55 mmHg for 80 minutes. MEASUREMENTS AND MAIN RESULTS:
      Measurements included plasma renin activity (RA) and plasma concentrations of
      angiotensin-II (AG-II), aldosterone (AS), norepinephrine (NE), and epinephrine
      (EP). These indices were measured before hemodilution, after hemodilution, 80
      minutes after starting hypotension, and 60 minutes after recovery from
      hypotension. Hemodilution alone caused no significant change in the values
      throughout the time course. Controlled hypotension alone caused significant
      increases in plasma concentrations of NE (+295%) and EP (+203%) at 80 minutes
      after starting hypotension, whereas it caused no change in plasma RA and plasma
      concentrations of AG-II and AS. Hemodilution plus controlled hypotension caused
      significant increases in plasma RA (+271%) and plasma concentrations of AG-II
      (+188%), AS (+199%), NE (+279%), and EP (+184%) at 80 minutes after starting
      hypotension. CONCLUSION: The combination of hemodilution and PGE1 induced
      controlled hypotension causes significant responses, especially in a renin
      angiotensin-aldosterone system under isoflurane anesthesia.

PMID- 9195358
TI  - Pseudocholinesterase hyperactivity with succinylcholine resistance: an unusual
      cause of difficult intubation.
AB  - We describe a case of difficult intubation, possibly due to marked
      pseudocholinesterase hyperactivity that caused rapid inactivation of
      succinycholine. Possible causes of difficult intubation and pseudocholinesterase
      hyperactivity are discussed. Literature on genetic variants associated with
      markedly increased pseudocholinesterase activity are reviewed. It is concluded
      that pseudocholinesterase hyperactivity may be a rare cause of difficult
      intubation. We recommend that pseudocholinesterase activity should be determined
      in all patients who appear to be resistant to the action of normal doses of
      succinylcholine or mivacurium.

PMID- 9195359
TI  - The effect of solubility and hyperlipidemia on perioperative arterial blood gas
      tensions.
AB  - A case is presented to illustrate the need for technical care when handling blood
      gas samples. The physics of solubility are used to show hour samples changed
      their oxygen tension (pO2) during handling, while investigating a clinical case
      to show the effect of hyperlipidemia on blood gases. It appeared that inadvertent
      access to air allowed atmospheric oxygen to equilibrate with the sample. The
      physical laws predicting the effect of partial pressure and temperature on gas
      solubility in a liquid are illustrated by the pO2 levels measured in this case.
      Effects due to hyperlipidemia were not observed. The calculations are described
      in detail. Brief suggestions for sample handling to avoid misleading results from
      such cases are discussed.

PMID- 9195360
TI  - The neurologic implications of diabetic hyperglycemia during surgical procedures
      at increased risk for brain ischemia.
AB  - The neurologic implications of diabetic hyperglycemia depend on whether the
      ischemic insult is permanent or temporary. Laboratory studies show that following
      permanent focal ischemia, a situation analogous to stroke, diabetic hyperglycemia
      is protective in the penumbral region, whereas it may slightly increase infarct
      size. In addition, clinical studies cannot unequivocally attribute poor outcome
      in diabetic stroke patients to hyperglycemia. Thus, both laboratory and clinical
      studies have been unable to define a cause and effect relationship between
      diabetic hyperglycemia and neurologic outcome following stroke. On the other
      hand, diabetic hyperglycemia is an important determinant of neurologic outcome
      following temporary focal ischemia (analogous to temporary occlusion of a
      cerebral vessel) and global ischemia (analogous to circulatory arrest). Based on
      laboratory studies, aggressive insulin-based blood glucose management with the
      goal of euglycemia is imperative prior to temporary ischemia. However,
      intraoperative ischemic events are overwhelmingly of a permanent focal nature,
      and the neurologic implications of diabetic hyperglycemia for the vast majority
      of surgical procedures at increased risk for brain ischemia are minimal. It is
      only in circumstances where temporary focal or global ischemia are used as part
      of the surgical procedure that aggressive insulin-based blood glucose management
      is warranted.

PMID- 9195361
TI  - A case of resident malpractice administering spinal anesthesia.

PMID- 9195362
TI  - Outpatient bone marrow harvesting.

PMID- 9195363
TI  - Gloves, laryngoscopes, and laryngeal masks.

PMID- 9195364
TI  - Case report: incomplete septal cirrhosis with liver cell dysplasia.
AB  - A 60-year-old woman was transplanted for end-stage alcoholic cirrhosis. The
      diagnosis of cirrhosis was made 13 years earlier on the basis of features of
      portal hypertension and a wedge liver biopsy. Liver function tests were subnormal
      except for a low prothrombin time. Unproven possible alcohol abuse was the only
      aetiological factor. Her condition remained unchanged until transplantation,
      despite complete abstinence. Histological examination of the explant showed
      incomplete septal cirrhosis associated with distal obstructive portal venopathy,
      cirrhotic nodules predominantly in the subcapsular areas and nodular regenerative
      hyperplasia with septal fibrosis elsewhere. In addition, there were areas of
      large and small liver cell dysplasia. This observation shows the difficulty in
      making a diagnosis of incomplete septal cirrhosis and the hypothetical link
      between liver cell dysplasia (which has never been reported in incomplete septal
      cirrhosis but is well known to be associated with hepatocellular carcinoma in
      cirrhosis) and rare cases of liver adenomas and carcinomas reported in patients
      presenting with liver vascular disorders.

PMID- 9195365
TI  - Hepatitis B infection and changes in interferon-alpha and -gamma production in
      patients with systemic lupus erythematosus in Taiwan.
AB  - According to previous reports, the prevalence of hepatitis B virus (HBV)
      infection in patients with systemic lupus erythematosus (SLE) is varied. There
      has been no report on Taiwan, a hyperendemic area for HBV infection. Furthermore,
      impaired production of interferon (IFN) in peripheral blood mononuclear cells
      (PBMC) has been reported to be potentially pathogenic to both chronic HBV
      infection and SLE. However, the production of IFN in patients with both diseases
      coexisting is unknown. The aims of this study were to evaluate the prevalence of
      HBV infection in lupus patients in Taiwan and to measure the production of IFN in
      patients with both diseases coexisting. One hundred and seventy-three consecutive
      lupus patients and a control group of 692 age- and sex-matched healthy subjects
      were included for evaluation of the prevalence of HBsAg. Four groups of subjects
      (patients with SLE and HbsAg, SLE, chronic hepatitis B and normal controls) were
      selected for evaluation of the in vitro production of IFN-alpha and -gamma. Six
      (3.5%) of the 173 SLE patients were positive for HBsAg, which was significantly
      lower than that of controls (14.7%; P < 0.0001). Patients with coexistent SLE and
      chronic HBV infection had less lupus activity, including less proteinuria (P =
      0.02) and a lower serum titre of anti-double stranded DNA antibodies (anti-dsDNA;
      P = 0.04), than HBsAg-negative lupus patients. The in vitro production of IFN
      alpha in patients with chronic hepatitis B was significantly lower than in those
      patients with SLE or in the normal control group (P < 0.01). The yields of IFN
      alpha and -gamma in patients with coexistent SLE and chronic HBV infection were
      significantly different from those patients with SLE alone (P < 0.05), but close
      to those of patients with chronic HBV infection. In conclusion, the prevalence of
      HBsAg carriers is significantly lower in lupus patients in Taiwan. Patients with
      coexistent SLE and chronic HBV infection had less lupus activity. Interferon
      alpha and -gamma may play a role in the above phenomenon.

PMID- 9195366
TI  - Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma.
AB  - This is a report of a phase II study of megestrol acetate (160 mg/day, orally) in
      the treatment of hepatocellular carcinoma (HCC). Forty-six patients with advanced
      HCC were studied and tumour response, changes in appetite, bodyweight, a feeling
      of well-being, survival and toxicity were evaluated. Thirty-two patients were
      able to be evaluated for response; there were no complete responders or partial
      responders. Twelve patients (38%) had stable disease and seven of these patients
      had a minor response with a median size reduction in the tumour of 18%. Twenty
      patients (62%) had progressive disease. Five of 24 (21%) patients had a median
      reduction in alpha-fetoprotein levels of 59 ng/mL. The overall median survival
      was 4 months (range 1 week to 27 months). Twenty of 32 (62%) patients had an
      increased appetite and feeling of well-being. Fourteen of 22 (64%) patients had a
      median lean bodyweight gain of 5 kg (range 1-14 kg). Toxicities were minimal.
      Tests for glucocorticoid receptors were performed in 10 patients. Four of five
      patients who were positive for glucocorticoid receptors in the tumour had a
      stable disease and all five patients who were negative for glucocorticoid
      receptors had progressive disease. Megestrol acetate had no significant effect on
      the tumour in HCC patients. However, megestrol acetate is useful in the
      palliative management of HCC patients, with improvements in appetite, bodyweight
      and a feeling of well-being with minimal side effects. Some patients had stable
      disease, a minor reduction of tumour size and a prolonged survival after
      megestrol acetate treatment and this response may be related to the presence of
      glucocorticoid receptors in the HCC tumour.

PMID- 9195367
TI  - Review: nutritional support for patients with cirrhosis.
AB  - Nutritional support is indicated when cirrhotic patients undergo surgery because
      they are malnourished, hypercatabolic and immunocompromised. However, the choice
      of nutrient may be problematic as the liver itself is the central organ of
      protein, fat and glucose metabolism. Branched chain amino acid-enriched solution
      may be the choice of protein source, as it is anticatabolic and it stimulates
      liver regeneration. Excessive glucose is undesirable as it may suppress
      endogenous fat utilization, which may be the preferred pathway of metabolism
      after hepatectomy. Medium chain triglycerides are preferred to long chain
      triglycerides as they are readily utilized and are not deposited in the liver;
      however, the tendency of cirrhotic patients to accumulate free fatty acids and
      glycerol after infusion of triglycerides dictates their use intermittently.
      Clinical studies have shown that perioperative nutritional support is beneficial
      in cirrhotic patients undergoing major hepatectomy or liver transplantation. The
      judicious choice of nutrient, care of the catheter and a limitation of the fluid
      infused are all prerequisites for the efficient use of perioperative nutritional
      support, which is complementary to a technically perfect operation.

PMID- 9195368
TI  - Case report: cytomegalovirus infection as a cause of acute portal vein
      thrombosis.
AB  - We report on the case of a 31-year-old woman who developed acute portal vein
      thrombosis during the course of an acute cytomegalovirus (CMV) infection. We
      suggest a relationship between CMV infection, its endothelial cell-damaging
      effects and portal vein thrombosis.

PMID- 9195369
TI  - Review: hepatitis delta.
AB  - The causative agent of hepatitis delta virus (HDV) is the most unusual of all
      causative agents for all hepatitis viruses. Current knowledge of the molecular
      biology of HDV strengthens its proposed classification within the satellites, a
      family of subviral agents, some of which are pathogens of higher plants.
      Hepatitis delta virus is the only virus in the satellite family known to infect
      animal species, with hepatitis D having affected more than 10 million people
      worldwide who are also infected with its helper virus, HBV. Recently, the world
      map for hepatitis D appears somewhat modified, with decreasing HDV prevalence in
      certain areas and some new foci of HDV endemicity. Despite changing HDV
      prevalence, hepatitis. D, particularly the chronic form, is still an important
      health problem worldwide in terms of morbidity and mortality (mainly due to
      chronic liver disease, including hepatocellular carcinoma). Molecular studies
      have greatly advanced our understanding of the life cycle of HDV and of the
      function of its proteins. The new molecular information is of clinical relevance,
      with implications for the pathogenesis of liver damage, the diagnosis of HDV
      infection, for the natural course of the disease and, potentially, for therapy.
      Sensitive assays for HDV-RNA by polymerase chain reaction and sequencing
      techniques have clarified the patterns of HDV transmission and have confirmed the
      existence of unusual clinical forms of the virus and their relationship to
      replicative levels and genotypes of HDV. Prevention and treatment of hepatitis D
      are still in their infancy. However, liver transplantation for delta cirrhosis
      has proven far more successful than in any other viral form of cirrhosis, with
      few reinfections of the grafted liver, and has given important information on HDV
      biology and the pathogenesis of liver damage.

PMID- 9195370
TI  - Seroepidemiological study on hepatitis delta virus infection in the Irabu
      Islands, Okinawa, Japan.
AB  - A seroepidemiological study was performed to clarify the prevalence of hepatitis
      delta virus (HDV) infection among the general population in the Irabu islands,
      Okinawa, Japan. Of 2028 healthy people examined who had received their annual
      health check-up in 1994-95, 195 (9.6%) were positive for hepatitis B surface
      antigen (HBsAg). Of these 195 HBsAg-positive individuals, 46 (23.6%) showed a
      positive reaction for antibody to HDV (anti-HDV). The positivity rate of anti-HDV
      among HBsAg-positive subjects tended to increase with age up to 50-59 years of
      age. The prevalence of anti-HDV also varied among the seven districts in the
      islands (0-63.3%). None of the anti-HDV-positive subjects was included in the
      high risk group for parenterally transmitted diseases. The unusually high
      prevalence of anti-HDV among HBsAg-positive individuals, particularly in the
      older age groups, seemed to reflect the natural prevalence or previous HDV
      infection, rather than a current or imported infection of HDV. Although the great
      majority of HBsAg-positive subjects with anti-HDV were asymptomatic, abnormally
      high values of serum transaminases were more frequently seen in these subjects
      compared with HBsAg-positive subjects without anti-HDV.

PMID- 9195371
TI  - Ethanol feeding enhances inflammatory cytokine expression in lipopolysaccharide
      induced hepatitis.
AB  - Elevated concentrations of plasma tumour necrosis factor (TNF)-alpha, interleukin
      (IL)-1 and IL-6 have been detected in patients with alcoholic hepatitis and have
      been implicated in the pathogenesis of hepatocyte necrosis. The present study
      used a rat model to conduct a detailed histological and biochemical examination
      of the expression of various pro-inflammatory cytokines and associated liver
      pathology in ethanol-potentiated lipopolysaccharide (LPS)-induced liver injury.
      Male Wistar rats were pair-fed either the control or ethanol-containing (36% of
      caloric intake as ethanol) form of the Lieber-DeCarli liquid diet for 6 weeks.
      Liver injury was induced by the i.v. injection of LPS (1 microgram/g bodyweight),
      with animals being killed at 0, 1, 3, 6, 12 and 24 h after injection. At the
      later time points, plasma transaminase and transpeptidase activities were
      significantly elevated in ethanol-fed LPS-treated rats compared with control-fed
      LPS-treated animals. At these times after LPS treatment, hepatocytes in ethanol
      fed animals displayed fatty change and necrosis with an associated neutrophil
      polymorph infiltrate. Time course analysis revealed that plasma TNF-alpha (1-3 h
      post-LPS) and IL-6 (3 h post-LPS) bioactivity was significantly elevated in
      ethanol-fed compared with control-fed animals. No difference was seen in plasma
      IL-1 alpha concentration (maximal in both groups 6 h post-LPS). The expression of
      TNF-alpha, IL-1 alpha, IL-1 beta and IL-6 mRNA were elevated between 1 and 6 h
      post-LPS in the livers of both control and ethanol-fed rats. However, ethanol-fed
      LPS-treated animals exhibited significantly higher maximal expression of IL-1 and
      IL-6 mRNA. Comparison of the appearance of cytokine mRNA and plasma bioactivity
      indicated an effect of ethanol feeding on post-transcriptional processing and/or
      the kinetics of the circulating cytokines. Elevated levels of both hepatic
      cytokine mRNA expression and the preceding plasma cytokines are presumably a
      necessary prerequisite for hepatic injury seen in this model and, therefore,
      possibly for the damage seen in human alcoholics. Further studies using this
      model may lead to significant advances in our understanding of the pathogenic
      mechanisms of alcoholic liver disease in humans.

PMID- 9195372
TI  - Endothelin-induced vasoconstriction in isolated perfused liver preparations from
      normal and cirrhotic rats.
AB  - Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon
      tetrachloride-induced cirrhosis and normal controls, were used to investigate
      responses to the vasoactive peptide endothelin-1 (ET-1). The mean perfusion
      resistance (R) of cirrhotic IPRL was significantly greater than that of controls
      (2.63 +/- 0.24 vs 1.54 +/- 0.14 mmHg/mL per min per g; P < 0.01). Both control
      and cirrhotic IPRL demonstrated a concentration-related increase in resistance
      (delta R) in response to ET-1, with a minimum effective concentration of
      approximately 3 x 10(-11) mol/L. The EC50 (-log of the 50% effective
      concentration) was not significantly different between cirrhotic and control IPRL
      (8.48 +/- 0.19 and 8.79 +/- 0.11, respectively); however, the maximum response to
      ET-1 was significantly greater in cirrhotic preparations (R: 10.4 +/- 2.2 vs 4.4
      +/- 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 +/- 2.1 vs 2.8 +/- 0.4 mmHg/mL
      per min per g, P < 0.01). Following maximal stimulation by ET-1, the mean portal
      hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g
      was approximately 90% greater across cirrhotic IPRL than that across normal IPRL
      (11.2 +/- 2.0 vs 5.9 +/- 0.9 mmHg, respectively; P < 0.05). These results support
      the hypothesis that endogenously released ET-1 has a significant influence on the
      portal vascular resistance of cirrhotic liver in vivo and has an important role
      in the pathogenesis of portal hypertension.

PMID- 9195373
TI  - Susceptibility of experimental autoimmune hepatitis in transgenic mice
      overexpressing the c-H-ras gene.
AB  - Results from a recent study of ours have demonstrated the significant role of the
      wild-type ras gene in the development of hepatocellular carcinoma in rasH2 mice
      having prototype human c-H-ras genes. Chronic cell death and regeneration have
      been considered to work as co-carcinogens with wild-type ras gene overexpression
      in this model. To elucidate a role of gene overexpression in the occurrence of
      chronic inflammation, we tried to induce inflammation in the liver of rasH2 mice
      by immunizing them with the supernatant of a freshly prepared syngenic liver
      homogenate. Immunization resulted in a dense inflammatory infiltrate in the
      portal tract and focal necrosis with spots of fatty or foamy degeneration in the
      transgenic mouse liver; however, these observations were less frequently observed
      in non-transgenic mouse liver. Monocytes, granulocytes and plasma cell
      infiltration were observed in the livers of transgenic mice. An
      immunohistochemical study showed that CD3-positive lymphocytes also infiltrated
      the liver. The inflammatory infiltrate was still present in the transgenic liver
      24 weeks after the last injection, but little infiltrate was observed at the same
      time in non-transgenic mice. No hepatic tumours could be produced over the 6
      months duration of the study and the results are only preliminary. However, these
      results do suggest that overexpression of wild-type ras is partially responsible
      for the occurrence of autoimmune chronic hepatitis.

PMID- 9195374
TI  - Dimethylsulfoxide maintains intercellular communication by preserving the gap
      junctional protein connexin32 in primary cultured hepatocyte doublets from rats.
AB  - Intercellular communication via gap junctions is one of the differentiated
      functions of cells. Dimethylsulfoxide (DMSO) is known to induce cell
      differentiation and maintain differentiated cellular functions in primary
      hepatocyte culture, but the mechanism of action of DMSO is unknown. Therefore, we
      investigated the effect of DMSO on cell-cell communication via gap junctions of
      hepatocyte doublets, which are differentiated cells that lose differentiated
      functions with time in culture. In isolated rat hepatocyte doublets, we assessed
      the effects of 1, 2 and 3% DMSO in culture medium on morphological changes and
      dye-coupling activity between pairs of cells by microinjection with fluorescent
      dye (Lucifer Yellow CH). The distribution of gap junction protein connexin32
      (Cx32) was assessed by indirect immunofluorescence analysis and the Cx32 mRNA was
      detected by the reverse transcription-polymerase chain reaction method.
      Dimethylsulfoxide delayed the morphological change of hepatocyte doublets from a
      spherical to a flattened shape. Dye-coupling efficiency significantly decreased
      with time in culture in the control group, whereas in groups treated with 2 and
      3% DMSO, dye-coupling efficiency was retained after 6 and 9 h of inoculation (P <
      0.05 and P < 0.01, respectively). Analysis by indirect immunofluorescence showed
      few fluorescent spots for Cx32 in the control group at 9 h of incubation, whereas
      many punctate fluorescent spots were seen in the 3% DMSO group at 9 h of
      incubation. The detection of Cx32 mRNA in the 3% DMSO group was also stronger
      than in controls. Dimethylsulfoxide significantly maintained intercellular
      communication via gap junctions in primary cultured rat hepatocytes through the
      preservation of functional Cx32 protein, thus maintaining cell differentiation.

PMID- 9195376
TI  - Endoscopic variceal ligation. A new era of variceal treatment is opened.

PMID- 9195375
TI  - Therapeutic results of endoscopic variceal ligation for acute bleeding of
      oesophageal and gastric varices.
AB  - Endoscopic variceal ligation (EVL) using 'O' rings is widely accepted as a
      treatment of oesophageal varices that is at least as effective as endoscopic
      injection sclerotherapy but which produces fewer complications. Endoscopic
      variceal ligation using detachable snares has attracted attention as a safe and
      easy method of endoscopic treatment for gastric varices. Nineteen patients with
      acute bleeding from oesophageal or gastric varices were treated in the present
      study. Of these, 14 patients were treated with EVL using 'O' rings and five
      patients were treated with EVL using detachable snares and the treatment results
      were evaluated. Haemostasis was achieved in all patients. No serious
      complications of the procedures were observed. However, recurrences and
      rebleeding were observed in some patients during the maximum follow-up period of
      24 months. Endoscopic variceal ligation using 'O' rings and detachable snares is
      useful for achieving haemostasis in cases of acute bleeding from oesophageal or
      gastric varices. However, additional endoscopic sclerotherapy may be needed to
      eliminate the variceal feeding vessels to further improve the long-term prognosis
      of these patients.

PMID- 9195377
TI  - Enhanced motility of the vagotomized canine stomach by electrical stimulation.
AB  - Functional impairment of the vagotomized stomach used as a substitute oesophagus
      seriously deteriorates the quality of life of patients following oesophageal
      cancer surgery. We speculated that if the enteric neurons of the reconstructed
      gastric tube survived functionally, the motility of the gastric tube could be
      facilitated and the recovery process after operation would improve as a
      consequence. In the present study we investigated whether direct electrical
      stimulation was effective for facilitating the motility of the canine vagotomized
      stomach. Dogs underwent truncal vagotomy by transabdominal approach and, in some
      cases, arteries to the upper stomach and the oesophagus were also ligated and
      resected to resemble the blood supply and surgical invasion of the reconstructed
      gastric tube. Electrical stimulation, a few minutes of positive rectangular
      current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between
      0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes
      in mechanical contractions were recorded using strain gauge force transducers.
      Electrical stimulation successfully enhanced the mechanical force of the phasic
      ring contractions of the vagotomized stomach in a frequency dependent manner.
      Aboral propagation and periodicity of the contractions, impaired by surgical
      procedures, were restored during stimulation. These excitatory effects were
      inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical
      stimulation acts on intramural cholinergic nerves that have survived
      functionally. These results suggest that electrical stimulation could be an
      effective method for improving the motility of the vagotomized stomach.

PMID- 9195378
TI  - Brief communication: smoking and duodenal blood flow.
AB  - Smoking promotes an increase in both the incidence and the recurrence of duodenal
      ulcers, but the mechanisms responsible for its adverse effects on the duodenal
      mucosa are still poorly understood. The aim of the present study was to
      investigate the effect of chronic cigarette smoking on duodenal blood flow. In 20
      dyspeptic patients (10 non-smokers and 10 smokers) with endoscopically normal
      duodenum, mucosal blood flow was measured in the duodenal bulb by laser Doppler
      flowmetry during endoscopy. Basal bulbar perfusion was found to be significantly
      lower (P < 0.05) in smokers. Our results suggest that duodenal blood flow is
      reduced in heavy smokers. This may promote duodenal damage because of both local
      ischaemia and the reduced secretion of protective bicarbonate.

PMID- 9195379
TI  - Case report: a case of primary ileal carcinoma in a young woman and a review of
      the Japanese literature.
AB  - We report a case of primary ileal carcinoma in a young woman, which was diagnosed
      definitively before operation. A 29-year-old woman presented with abdominal pain,
      diarrhoea and bloody stools. Colonoscopic and radiographic studies revealed that
      there was a 7.5 x 7 cm tumour (well-differentiated adenocarcinoma) at the
      terminal ileum, forming an ulcerated lesion at the centre. The tumour had invaded
      the caecum, the right urinary tract, the right ovary and a portion of the sigmoid
      colon. Fifty-three cases of primary ileal carcinoma were reported in Japan
      between 1982 and 1994 and their clinical features are reviewed herein.

PMID- 9195380
TI  - Cytoprotective effect of epidermal growth factor on acid- and pepsin-induced
      damage to rat gastric epithelial cells: roles of Na+/H+ exchangers.
AB  - We have previously established a cell damage model, with damage induced by either
      acid or pepsin treatment for 30 min, involving a rat gastric epithelial cell line
      (RGM1). In the present study, pretreatment of cells with epidermal growth factor
      (EGF; 0.1-10 ng/mL) or sucralfate (0.1-3 mg/mL) for 4 h prevented such cell
      damage in a concentration-dependent manner. Protection of cells by these drugs
      was not affected by pretreatment with indomethacin (10(-5) mol/L) for 4 h.
      Removal of Na+, but not Ca2+, from the acidified medium totally abolished the
      inhibitory effect of EGF, but not that of sucralfate. Genistein (a tyrosine
      kinase inhibitor) apparently reduced the inhibitory effect of EGF. DNA synthesis
      by RGM1 cells did not increase when cells were incubated with EGF for 4 h. We
      conclude that both EGF and sucralfate protect RGM1 cells from acid- and pepsin
      induced damage and that the mechanism of protection by EGF against acid-induced
      damage seems to be via activation of Na+/H+ exchangers.

PMID- 9195381
TI  - Analysis of pathogenic elements involved in gastric lesions induced by non
      steroidal anti-inflammatory drugs in rats.
AB  - Pathogenesis of gastric damage induced by non-steroidal anti-inflammatory drugs
      (NSAID) involves multiple elements, such as deficiency of prostaglandins (PG),
      gastric hypermotility, neutrophil activation and luminal acid. The present study
      was performed to examine the effects of these elements, either alone or in
      combination, on the rat gastric mucosa and investigate which element is most
      closely associated with the gastric ulcerogenic response to NSAID. The following
      treatments were used to express various pathogenic elements: (i) a low dose of
      indomethacin (IM) to cause PG deficiency; (ii) 2-deoxy-D-glucose (2DG) to induce
      gastric hypermotility and acid secretion; (iii) histamine to induce acid
      hypersecretion; and (iv) n-formyl-Met-Leu-Phe (fMLP) to elicit neutrophil
      activation. When rats fasted for 18 h were subjected to each treatment alone,
      only 2DG caused slight macroscopic damage in the gastric mucosa within 4 h.
      Indomethacin showed over 90% inhibition of mucosal PG generation and fMLP
      increased myeloperoxidase activity four-fold greater than normal values, yet
      either of these treatments alone did not cause any damage in the stomach.
      However, the combination of IM with 2DG or His provoked severe lesions in the
      stomach or the duodenum, respectively, while fMLP did not modify or potentiate
      the mucosal ulcerogenic response to other treatments. We conclude that among
      various pathogenic elements only gastric hypermotility is sufficient, by itself,
      to induce mild damage in the mucosa, that PG deficiency may be critical in the
      increase of mucosal susceptibility to injury and that neutrophil activation alone
      is not ulcerogenic in the gastric mucosa nor does it potentiate the ulcerogenic
      effect of other elements. Luminal acid may be a prerequisite for later extension
      of damage to severe lesions.

PMID- 9195382
TI  - Analysis of interleukin-8 secretion induced by Helicobacter pylori from the
      gastric epithelial cell line MKN45: a mechanism independent of the intensity of
      cytotoxicity.
AB  - Interleukin (IL)-8, a potent chemoattractant and activator of neutrophils, has
      been implicated to have a major role in the pathogenesis of gastric mucosal
      injury by Helicobacter pylori infection. We examined the relationship between
      cytotoxicity and IL-8 secretion induced by H. pylori. Furthermore, whether the
      vacuolating cytotoxin of H. pylori mediates IL-8 secretion from gastric
      epithelial cell lines was examined. Among the inflammatory cytokines, messages
      for IL-6, IL-8 and transforming growth factor-beta 1 were produced by gastric
      cancer (MKN45) cells in response to exposure to the cytotoxic strain of H.
      pylori. MKN45 incubated with the viable cytotoxic strain of H. pylori secreted IL
      8. In contrast, the supernatant of neither the cytotoxic nor the non-cytotoxic
      strain induced IL-8 secretion. There was no correlation between IL-8 secretion
      and the intensity of cytotoxicity. In conclusion, these findings suggest that IL
      8 secretion from MKN45 induced by H. pylori is mediated by factors other than
      cytotoxicity.

PMID- 9195383
TI  - A rapid and simple method to quantify Helicobacter pylori adhesion to human
      gastric MKN-28 cells.
AB  - A rapid and simple method to quantitatively analyse Helicobacter pylori adhesion
      to human gastric epithelial cells was developed by using an enzyme-linked
      immunosorbent assay. This method made it possible to quantitatively evaluate the
      adhesion activities of many different H. pylori strains at a time. Our studies
      indicate that this method is well suited for the quantitative analysis of H.
      pylori adhesion to gastric epithelial cells.

PMID- 9195384
TI  - Effect of ageing on pancreatic hyperplasia after 90% proximal small bowel
      resection.
AB  - The present study was performed to examine the effect of ageing on pancreatic
      hyperplasia observed after proximal small bowel resection (PSBR). Young and old
      Wistar rats were randomly assigned to two groups, which underwent either an
      approximate 90% PSBR or a jejunal and ileal transection (TRC). One week after the
      operation, the pancreatic wet weight and the protein, DNA and RNA content of the
      pancreas were all significantly higher in young PSBR rats than in young TRC rats.
      However, no differences were seen in the old rat groups. Plasma enteroglucagon
      levels were elevated in both young and old PSBR rats, but the ratio of increase
      between the PSBR and TRC groups was significantly higher in young rats. Plasma
      cholecystokinin and gastrin levels did not increase after PSBR in either the
      young or old rats. These findings suggest that pancreatic hyperplasia observed
      after PSBR is attenuated by ageing, probably due to an insufficient increase in
      plasma enteroglucagon levels.

PMID- 9195385
TI  - Case report: life-threatening haematochezia from a jejunal leiomyoma.
AB  - Leiomyoma is a common benign intestinal tumour. Melaena is not rare in this
      tumour. Recently, rectal haematochezia has been considered as one of the very
      rare manifestations of leiomyoma. We report a case of jejunal leiomyoma showing
      life-threatening rectal bleeding. This 76-year-old man was admitted to hospital
      because of continuous rectal bleeding for 2 days. Haemorrhagic shock occurred and
      transfusion of 27 units of packed red blood cells failed to correct the shock.
      Emergent superior mesenteric angiography revealed a distal jejunal tumour showing
      evidence of active oozing. Segmental intestinal resection was performed to remove
      this jejunal tumour. Final pathological examination disclosed a jejunal leiomyoma
      with a ruptured artery responsible for the life-threatening bleeding. The patient
      recovered after tumour resection. Our presenting case was probably the second
      case of jejunal leiomyoma showing haematochezia. The diagnostic priority is
      discussed.

PMID- 9195386
TI  - Use of spiral and non-spiral computed tomography arterial portography in the
      detection of potentially malignant liver masses.
AB  - The present study assesses the usefulness of computed tomography (CT) arterial
      portography (CTAP) in detecting and defining the number and anatomy of
      potentially malignant liver lesions. One hundred and one adults studied in 1993
      and 1994 were retrospectively reviewed, including patients with primary or
      secondary tumours for possible resection and patients with non-hepatic
      malignancies in whom the detection of liver metastases would preclude surgery.
      Twenty-three patients underwent non-spiral CT studies and 78 had studies on a
      spiral unit, with 22 of these having single phase and 56 having dual phase
      studies to overcome artefact problems. The relationship between lesion size and
      detection sensitivity is critical. On non-spiral studies, the overall lesion
      detection sensitivity and positive predictive value was 69 and 90%, respectively.
      Detection sensitivity was 100 and 20% for lesions > 1 cm and < 1 cm,
      respectively. On single phase spiral CTAP the overall detection sensitivity and
      positive predictive value was 80 and 66%, respectively. Detection sensitivity for
      lesions > 1 cm and < 1 cm was 100 and 0%, respectively. On dual phase spiral CTAP
      the overall detection sensitivity and positive predictive value was 76 and 71%,
      respectively. For lesions > 1 cm and < 1 cm the sensitivity was 81 and 55%,
      respectively. Eighteen patients with non-hepatic malignancies with unsuspected
      metastatic spread did not proceed to major surgery because of liver metastases
      detected on CTAP. Perfusion artefacts occurred in 30 and 64% of non-spiral and of
      initial portal venous spiral CTAP studies, respectively. By using the double
      phase technique, these artefacts were substantially diminished. In conclusion,
      CTAP is a valuable tool for assessing the presence, site and size of possible
      liver tumours and confers a benefit even when previous ultrasound and
      conventional CT have already been used. In addition, CTAP has a lower limit of
      useful resolution of approximately 1 cm. Perfusion artefacts can be reduced by a
      dual phase protocol.

PMID- 9195387
TI  - Case report: right-sided periadrenal metastasis supplied by the hepatic artery.
      Clue to the genesis of pedunculated hepatocellular carcinoma.
AB  - The adrenal is the second most common site of haematogenous metastasis of
      hepatocellular carcinoma (HCC). The right adrenal is much more frequently
      affected than the left, but no reason has been offered for this difference. An
      aetiological connection has never been suggested between adrenal metastasis and
      pedunculated HCC. Hepatocellular carcinoma was resected in two patients who
      subsequently developed right-sided adrenal metastasis diagnosed by imaging. The
      adrenal mass was enhanced by hepatic arteriography and took up lipiodol injected
      into the hepatic artery. Reoperation was performed to remove the adrenal mass,
      which was abutting on the liver but was readily separable. Histopathologically,
      the adrenal gland was compressed by a metastatic HCC that developed in the
      immediate periadrenal tissue or adrenal capsule. By conventional imaging, the
      adrenal gland could not be recognized and the mass was thought to have arisen
      within the adrenal gland. In conclusion, periadrenal growth of HCC is a hitherto
      unrecognized type of metastasis and must have been mistaken either for an adrenal
      metastasis or a pedunculated HCC in the past. If left unresected, it would have
      fused with the liver and grown into a pedunculated HCC. Cancer cell invasion
      through an adrenohepatic fusion is the most likely mode of periadrenal
      metastasis; it explains the arterial communication between the mass and the
      liver.

PMID- 9195388
TI  - Review: nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined
      clinicopathological entity; it has been reported more commonly in women than in
      men or children of both sexes and it appears to be most closely associated with
      obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and
      hyperglycaemia. However, the association with female gender, obesity and diabetes
      may not be as close as suggested by the literature and an underlying condition
      cannot be discerned in all cases. The natural history of the disease is poorly
      understood; the associated biopsy features span a wide spectrum, reaching from
      uncomplicated, clinically non-progressive fatty liver (not NASH in a strict
      sense) to a slowly progressive fatty liver with inflammation and fibrosis, to
      steatohepatitis with submassive hepatic necrosis, which has a subfulminant course
      and is often fatal. Non-progressive fatty liver appears to be very common but is
      of little clinical importance. The slowly progressive form of the disease
      represents NASH as encountered by most clinicians and pathologists. It is a
      common liver disease in current practice; patients may present with cirrhosis and
      even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become
      exceedingly rare because many clinicians are now aware of the hazards of sudden
      weight loss, particularly in morbidly obese patients. Treatment options for NASH
      are still limited. The promotion of gradual weight loss in obese patients is the
      most widely recommended therapy but, unfortunately, this is very difficult to
      achieve. Avoidance of precipitous weight loss and careful control of diabetes
      mellitus are important and undisputed parts of patient management. Administration
      of UDCA as a treatment of NASH is still under study; it may be effective in some
      patients. The treatment of established steatohepatitic cirrhosis does not differ
      substantially from that of other types of cirrhosis and includes orthotopic liver
      transplantation.

PMID- 9195389
TI  - Review: alpha 1-antitrypsin deficiency associated liver disease.
AB  - alpha 1-Antitrypsin (alpha 1-AT) deficiency is the most common genetic cause of
      liver disease in children and genetic disease for which children undergo liver
      transplantation. It also causes cirrhosis and hepatocellular carcinoma in adults.
      Studies by Sveger in Sweden have shown that only a subgroup of the population
      with homozygous PiZZ alpha 1-AT deficiency develop clinically significant liver
      injury. Other studies have shown that the mutant alpha 1-AT Z molecule undergoes
      polymerization in the endoplasmic reticulum and that a subpopulation of alpha 1
      AT-deficient individuals may be susceptible to liver injury because they also
      have a trait that reduces the efficiency by which the mutant alpha 1-AT Z
      molecule is degraded in the endoplasmic reticulum.

PMID- 9195391
TI  - Past, present and future of gastroenterology in Japan: the 100th anniversary of
      the Japanese Society of Gastroenterology in 1998.
AB  - The Japanese Society of Gastroenterology (JSGE) will celebrate the centenary of
      its foundation in 1998. A variety of plans and projects are being prepared by the
      JSGE centennial celebration committee. In this article, the history of the JSGE
      is briefly described, and several projects, including the international symposium
      currently being planned, are introduced. The future prospects of our Society will
      also be described.

PMID- 9195390
TI  - Portosystemic encephalopathy.

PMID- 9195392
TI  - The Gastroenterological Society of Australia.
AB  - In this review, a summary of the objectives and activities of The
      Gastroenterological Society of Australia is given. It illustrates the
      multidisciplinary and multi-functional roles of a society that is confident and
      active in supporting and reflecting the views of its members in the pursuit of
      excellence in clinical practice, research and education in the various areas of
      digestive health.

PMID- 9195393
TI  - Current topics on digestive disease in Korea.
AB  - This is a summary of the research topics, of current interest, relating to
      digestive disease in Korea. This review is based on the subjects of the papers
      that were accepted for presentation at the 34th Annual Meeting of the Korean
      Society of Gastroenterology and the 39th Semiannual Meeting of the Korean Society
      of Gastrointestinal Endoscopy held November 22-24, 1995, in Seoul. The most
      popular topics were on Helicobacter pylori infection. These included experimental
      papers on the pathogenesis of bacteria-associated gastritis and the duodenal
      ulcer. Recently, the increase in the number of papers published on the motility
      of the gastrointestinal and pancreaticobiliary tracts is quite remarkable.
      Molecular genetic works on oncogenesis using cultured tumour cell lines, on the
      enzyme expression in the biopsied mucosal cells of the small intestine, and on
      the various expressions of viral genomes in the hepatocytes are among these
      recent topics of research. Clinical works, such as therapeutic endoscopy in
      malignant diseases and therapeutic trials in the hepatitis virus-associated
      chronic liver diseases are also popular topics.

PMID- 9195394
TI  - An overview of gastrointestinal and hepatobiliary diseases in Thailand.
AB  - This review article discusses the present state of gastrointestinal and
      hepatobiliary diseases in Thailand. Comparisons are made with Western countries
      and more specific diseases such as hepatoma, cholangiocarcinoma and liver
      abscesses are also described.

PMID- 9195395
TI  - Development of gastroenterology in Bangladesh.
AB  - Diseases of the gastrointestinal tract and liver are very common in Bangladesh.
      Gastroenterology as a dedicated specialty was initiated in 1977 at the Institute
      of Postgraduate Medicine and Research in Dhaka. One more centre was set up later
      and these centres are providing specialized diagnostic and therapeutic services.
      These centres are also imparting training in endoscopy and 49 endoscopists
      trained so far are providing services in 22 centres around the country. Clinical
      gastroenterologists are also being trained in a 3 year Master's degree course and
      three specialists have already completed this. A Gastroenterology Society was
      formed in 1988 and has held three national scientific conferences and 20 regional
      meetings. Research in special problems of the country has also been initiated and
      work on aspects of peptic ulcer disease, chronic calcific pancreatitis and
      chronic viral hepatitis has been conducted. The demand for gastrointestinal
      services is high and the specialty has attracted a good number of young doctors.
      Gastroenterology is likely to grow in size and quality in Bangladesh.

PMID- 9195396
TI  - Some peculiarities of hepatobiliary diseases in Vietnam.
AB  - The most frequent hepatobiliary diseases in Vietnam are chronic hepatitis and
      cirrhosis, liver abscess, hepatobiliary ascaridiasis, angiocholitis, biliary
      lithiasis and primary liver cancer. The principal causes of chronic hepatitis and
      cirrhosis are HBV and HCV infections. Alcohol and chemicals (drugs, agricultural,
      industrial, war herbicides) also play an important role. Malaria causes hepatitis
      and fibrosis lesions, however no cirrhotic lesions were observed. There are two
      categories of liver abscess, amoebic and cholangitic, often caused by
      ascaridiasis. Treatment of amoebic abscesses is, at first, non-surgical for small
      abscesses, often combined with ultrasound guided abscess puncture. Cholangitis
      abscesses are more serious and often require surgical intervention. Among the
      gallstones, only 15% are of the gall-bladder, the majority are choledocho- and
      intrahepatic-lithiasis, composed largely of calcium bilirubinate and are
      frequently caused by Ascaris-related cholangitis and the nucleation of Ascaris
      eggs. Forty-seven per cent of acute cholecystitis are acalculous, showing a
      higher frequency than in Western countries. Primary liver cancer is one of the
      most frequent malignancies in Vietnam. More than 90% of liver cancers are
      hepatocellular carcinomas. The principal causes are HBV infection, followed by
      HCV infection, aflatoxin, alcohol and chemicals. Recent efforts aiming at earlier
      diagnosis, by selective screening in high-risk groups, have used clinical
      surveillance, abdominal sonography and AFP level determination. Promising results
      were obtained in prevention trials by reducing the high AFP level of cirrhotic
      patients using a vegetal drug, Gacavit, and by treatment with percutaneous
      ethanol injection therapy, as an alternative therapeutic measure for liver tumour
      resection.

PMID- 9195397
TI  - Review: Helicobacter pylori. Current issues and new directions.
AB  - The present review outlines current management issues and controversies related
      to Helicobacter pylori infection. Clearance of this infection markedly reduces
      the likelihood of duodenal and gastric ulcer recurrence and may result in the
      regression of low grade primary gastric lymphoma. Recent therapeutic advances
      have seen the development of simpler drug regimens to treat H. pylori that have
      fewer side effects and are shorter in duration. Clearance of the infection can be
      achieved in 80-95% of patients treated, depending on the drug regimen used,
      compliance with medications and antibiotic sensitivity. In developed nations
      reinfection is uncommon after successful treatment. Data do not currently support
      treatment of this infection for non-ulcer dyspepsia or for the prevention of
      gastric cancer, although whether certain individuals or populations may benefit
      from such treatment remains to be clarified.

PMID- 9195398
TI  - Increased prevalence of Helicobacter pylori infection among patients affected
      with intestinal-type gastric cancer at non-cardiac locations.
AB  - Previous data on the association of Helicobacter pylori infection with gastric
      cancer by demographic or histological features are inconsistent due to a
      univariate analysis of limited case numbers. The aim of the present study was to
      determine such an association by the use of a large series of patients and
      multiple variables analysis. The serum IgG antibodies against H. pylori were
      measured in 397 patients with histologically verified gastric cancer. A multiple
      logistic regression analysis was used to define the association between
      seropositivity and demographic or tumour characteristics of gastric cancer. The
      overall seropositivity of H. pylori was 63%. In univariate analysis, the
      prevalence was significantly lower among patients with cardia (50%) or diffuse
      type (56.6%) cancers than those with non-cardia (64.8%) or intestinal-type
      (70.3%) cancer (P < 0.05 and P < 0.01, respectively). There was no statistical
      difference between H. pylori infection rate and gender, age or tumour stage. A
      multiple logistic regression analysis showed tumour location and histology
      remained significant factors associated with seropositivity of H. pylori with an
      odds ratio of approximately 2.0. Analysis of combined histology and location
      revealed that patients with intestinal-type cancer at non-cardia locations had
      the highest odds ratio of 3.93 (95% confidence interval (CI): 1.55-10.0) compared
      with the lowest odds ratio of 0.69 (95% CI: 0.30-1.62) in diffuse cardia cancer
      (P < 0.005). Our data indicate H. pylori infection in gastric cancer is
      independently affected by the histological subtype and by tumour location.

PMID- 9195399
TI  - Enteral branched-chain amino acids increase the specific activity of jejunal
      glutaminase and reduce jejunal atrophy.
AB  - Branched-chain amino acid (BCAA)-enriched nutrient solutions reduce gut atrophy
      associated with parenteral nutrition. We hypothesized that this effect was
      mediated by phosphate-dependent glutaminase. Thirty male Wistar rats (300-350 g)
      underwent a standardized surgical procedure and were then randomized into three
      groups to receive 6 days of ad libitum enteral nutrition. The animals were fed a
      solution of conventional nutrients, a solution of conventional nutrients enriched
      with 2.0% BCAA or a solution of conventional parenteral nutrients enriched with
      2.5% glutamine. When compared with rats fed conventional nutrients, rats fed BCAA
      and glutamine had less jejunal atrophy (P < 0.05) and a greater specific activity
      of phosphate-dependent glutaminase in the jejunum (131%; P < 0.05). It is
      concluded that enteral BCAA reduce atrophy of the jejunum via the generation of
      glutamine.

PMID- 9195400
TI  - Intestinal-type tumour in resected gastric remnant cancer.
AB  - Lauren's intestinal type of gastric cancer was proposed to be dependent on long
      term environmental factors and is always preceded by chronic premalignant change.
      A cohort study was performed and demonstrated an increased cancer risk of gastric
      remnant after gastric surgery for benign disease. It is generally believed that
      after gastrectomy the residual stomach has an environmental change and, thus,
      enters a neoplastic process. Based on the carcinogenic theory of intestinal-type
      tumour, it would be of interest to know whether the intestinal-type tumour is
      more common in gastric remnant cancer. Forty patients with gastric remnant cancer
      had gastrectomy in the Veterans General Hospital-Taipei. Another 683 patients
      with primary gastric carcinoma underwent resection and were used as controls. The
      clinical characteristics, tumour stage and intestinal-type tumour were analysed
      in gastric remnant cancer and were compared with the various portions of primary
      gastric carcinoma. Although the overall distribution of intestinal-type carcinoma
      in gastric remnant (45%) was no different to that of any other portion of stomach
      cancer, intestinal-type carcinoma was more common in the early stage of gastric
      remnant (73%) and distal stomach (73%), but not in the proximal stomach (50%),
      which was supposed to have the same characteristics as the gastric remnant
      because of identical anatomic location. More than expected, intestinal-type
      carcinoma in early gastric remnant cancer together with a long incubation
      interval between primary surgery and later tumour occurrence were compatible with
      the theory of carcinogenesis of intestinal-type carcinoma.

PMID- 9195401
TI  - Review: the controversy over the pathophysiology of ascites formation in
      cirrhosis.
AB  - The pathogenesis of renal sodium retention and ascites formation in cirrhosis is
      a subject of much controversy. The generally accepted 'peripheral arterial
      vasodilatation hypothesis' seems to best explain the mechanism of sodium
      retention and other clinical findings, such as the hyperdynamic circulation of
      cirrhosis. However, recent data in pre-ascites and in early ascites do not seem
      to conform to the peripheral arterial vasodilatation hypothesis. Sodium handling
      abnormalities can be demonstrated in pre-ascitic cirrhosis when patients are
      challenged with a sodium load, in the absence of systemic vasodilatation or
      arterial underfilling. Therefore, an alternative hypothesis with a direct
      hepatorenal interaction, acting via sinusoidal portal hypertension and/or hepatic
      dysfunction as the affector mechanism, is proposed to be the initiating event in
      renal sodium retention in cirrhosis. The second and later process is the
      development of systemic arterial vasodilatation, possibly due to the presence of
      excess systemic vasodilators and/or decreased responsiveness of the vasculature
      to endogenous vasoconstrictors. This, in turn, will lead to a relatively
      underfilled circulation with consequent activation of neurohumoral systems,
      promoting further renal sodium retention as described by the peripheral arterial
      vasodilatation hypothesis and ultimately leading to ascites. When compensatory
      natriuretic mechanisms fail, refractory ascites develops and hepatorenal syndrome
      sets in. Thus, renal sodium retention in cirrhosis is the result of interplay of
      many factors, with direct hepatorenal interaction predominating in earlier stages
      of the cirrhotic process, while systemic vasodilatation becomes a more important
      pathogenetic factor as the disease progresses.

PMID- 9195402
TI  - Gall-bladder wall thickening in patients with liver cirrhosis.
AB  - Gall-bladder wall thickening is commonly seen in patients with cirrhosis, but its
      exact causes have not been well established. We evaluated clinical, biochemical
      and haemodynamic data of patients with cirrhosis with respect to the presence of
      thickening of the gall-bladder wall. After excluding patients who presented with
      gallstones, acute or chronic cholecystitis, heart failure, a serum creatinine
      level greater than 2 mg/dL and/or a serum alanine aminotransferase level greater
      than 400 U/L, 77 patients with cirrhosis (75 male, two female; mean age 58 +/- 8
      years) were enrolled in the study. Clinical, biochemical, ultrasound and
      haemodynamic data were obtained in every patient. Forty-one (53%) of 77 patients
      with cirrhosis had gall-bladder wall thickening (> 4 mm). Compared with patients
      with a normal gall-bladder wall, patients with gall-bladder wall thickening had
      significantly lower serum albumin levels (3.6 +/- 0.6 vs 2.9 +/- 0.7 gm/dL,
      respectively; P < 0.05), a longer prothrombin time (13 +/- 6 vs 16 +/- 6 s,
      respectively; P < 0.05), more patients with Child-Pugh class C (6 vs 37%,
      respectively; P < 0.05) and more patients with ascites (8 vs 50%, respectively; P
      < 0.05). In addition, compared with patients with a normal gall-bladder wall,
      those patients with gall-bladder wall thickening had a higher hepatic venous
      pressure gradient (13.9 +/- 4.5 vs 17.1 +/- 4.1 mmHg, respectively; P < 0.01) and
      a lower systemic vascular resistance (SVR; 1144 +/- 332 vs 1010 +/- 318
      dyn.s/cm5, respectively; P < 0.05). Using a multivariate analysis, the presence
      of ascites and SVR lower than 900 dyn.s/cm5 were independently correlated with
      the presence of gall-bladder wall thickening, while a hepatic vein pressure
      gradient greater than 10 mmHg had only a marginally significant association. The
      presence of ascites, decreased SVR and portal hypertension are related to the
      occurrence of gall-bladder wall thickening in patients with cirrhosis, indicating
      that the development of gall-bladder wall thickening may be multifactorial.

PMID- 9195403
TI  - Interferon therapy of hepatitis C. Who to treat and for how long?

PMID- 9195404
TI  - Liver transplantation for hepatitis C-associated cirrhosis in a single Australian
      centre: referral patterns and transplant outcomes.
AB  - During the study period, 63 patients with hepatitis C virus (HCV) cirrhosis were
      referred to our unit for liver transplantation. All cases referred and
      transplanted were retrospectively examined. Eighty-six per cent of referred
      patients were male, 35% consumed alcohol in the harmful/hazardous range, 13% were
      infected with hepatitis B and 7% had hepatocellular carcinoma. Patients with
      sporadic infection were more likely to be born outside Australia and were an
      average of 10 years older than those with HCV acquired via intravenous drug use
      (P < 0.001). However, patients were an average of 12 years younger at referral if
      they consumed harmful amounts of alcohol than if they abstained (P = 0.002). We
      examined the impact of HCV on the outcome of 28 patients who underwent liver
      transplantation (mean follow up 25 months; range 3-76 months). The use of OKT3,
      HCV genotype and hepatitis B status were examined for their effect on HCV-related
      graft dysfunction. Three year survival was 84%, equivalent to a control group.
      Chronic HCV-related graft dysfunction occurred in 15 (56%) patients, of whom 10
      had an asymptomatic elevation in serum amino transferase, two had cholestatic
      hepatitis and three had severe hepatitis C that progressed onto chronic
      rejection. Hepatitis C virus genotype 1b tended to be associated with HCV graft
      dysfunction (5/6 type 1b vs 10/16 in non-type 1b). In conclusion, HCV is an
      increasingly common indication for liver transplantation. Alcohol and hepatitis B
      were frequently occurring cofactors in the referral cohort. Most patients
      referred were male, although the reason why is not clear. Transplantation offers
      a good medium-term outcome, despite the high incidence of HCV-associated graft
      dysfunction.

PMID- 9195406
TI  - Earlier loss of hepatitis C virus RNA in interferon therapy can predict a long
      term response in chronic hepatitis C.
AB  - To distinguish responders from non-responders early in interferon (IFN) treatment
      would be beneficial in patients with chronic hepatitis C. Those patients unlikely
      to respond would be spared the cost and hazard of prolonged treatment. Forty
      three chronic hepatitis C patients who had received IFN-alpha therapy (6-9 MU;
      six times weekly for 2 weeks followed by thrice weekly for 22 additional weeks)
      were randomly enrolled into the present study. Serially obtained sera were
      retrospectively tested for HCV-RNA by reverse transcription-polymerase chain
      reaction (Amplicor HCV) with a low limit detection of approximately 10(2)
      copies/mL. Genotypes were determined by type-specific primers. Sixteen subjects
      were defined as sustained responders (SR), who showed sustained loss of viraemia
      with normalized alanine aminotransferase values for at least 6 months of follow
      up after completion of therapy. The other 27 subjects were non-responders (NR),
      whose viraemia persisted during follow-up. Pretreatment serum HCV-RNA levels (P <
      0.0001) and the genotype (P < 0.01) were significant predictors for sustained
      response to IFN therapy. Hepatitis C virus RNA was detectable in only one (6%) SR
      and in 23 (85%) NR at the second week of therapy (P < 0.0001) and was detected in
      none of the SR subjects and in 18 (67%) NR at the fourth week of therapy (P <
      0.0001). Pretreatment viral load was correlated with the time until loss of
      viraemia. Multivariate analysis revealed that loss of viraemia at the second week
      of therapy was the strongest predictor for a long-term response, followed by the
      initial viral load and loss of viraemia at the fourth week of therapy. These
      findings suggest that it is possible to predict a long-term response to IFN as
      early as at the second and fourth weeks after the start of therapy by identifying
      the presence or absence of HCV-RNA with a sensitive assay.

PMID- 9195405
TI  - Quantitative analysis of interferon alpha/beta receptor mRNA in the liver of
      patients with chronic hepatitis C: correlation with serum hepatitis C virus-RNA
      levels and response to treatment with interferon.
AB  - We analysed the expression of interferon (IFN) alpha/beta receptor mRNA in the
      liver of patients with chronic hepatitis C and examined the relationship between
      the expression of this receptor gene and the level of hepatitis C virus (HCV)-RNA
      as well as the response to 16 weeks of 6 x 10(6) units IFN. The mean level of IFN
      alpha/beta receptor mRNA in patients with chronic HCV infection (expressed as
      delta cycle; 10.8 +/- 1.9 (mean +/- SD); n = 39) was significantly higher than
      that of control subjects (9.4 +/- 0.5; n = 6; P < 0.01). There was a significant
      negative correlation between the level of IFN alpha/beta receptor mRNA and serum
      HCV-RNA in 39 patients with chronic hepatitis C (R = -0.546; P < 0.01). The mean
      level of IFN alpha/beta receptor mRNA in six patients who showed a complete
      response to IFN therapy (12.3 +/- 1.6) was higher than that of 15 patients who
      failed to respond to therapy (10.1 +/- 1.5; P < 0.01). Our results are consistent
      with the suggestion that the anti-viral activity of IFN depends on the level of
      the IFN alpha/beta receptor on hepatocytes in patients with chronic hepatitis C.

PMID- 9195407
TI  - Review: Barrett's oesophagus in Taiwan.
AB  - Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower
      oesophagus which is acquired as a complication of chronic gastro-oesophageal
      reflux (GER). Various complications seen in the Barrett's oesophagus, such as
      peptic ulcer, stricture, adenocarcinoma are named as Barrett's ulcer, Barrett's
      stricture-and Barrett's carcinoma, respectively. It is now generally accepted
      that Barrett's oesophagus is an acquired condition resulting from chronic
      repetitive GER. The frequency of Barrett's oesophagus seems to be higher in
      Caucasian than in Oriental or Negro populations. There is a tendency towards
      increasing prevalence rates all over the world, including Taiwan, due to the
      Westernization of diet, rapid growth in the elderly population, obesity etc.
      Almost 6% of the patients who manifest heartburn in GI clinics in Taiwan now
      suffer from GER, which is almost similar to the 7% reported by Nabel, (USA) in
      1976. During the last 30 years, the incidence of esophageal adenocarcinoma has
      increased rapidly. Patients with Barrett's oesophagus have an increased risk of
      developing oesophageal adenocarcinoma and should be kept under surveillance.
      Regular follow-up, at least twice a year or preferably, every 2-3 months, for
      those patients with SCE using endoscopic surveillance and biopsy for those with
      severe dysphasia (oesophageal columnar intraepithelial neoplasia) in the
      surrounding area to detect Barrett's oesophagus cancer, is very important.

PMID- 9195408
TI  - Peptic ulcer disease in the 1990s: an Asian perspective.
AB  - Peptic ulcer disease is still a common disease in many parts of Asia, although it
      is less common today than it was 2-3 decades ago. Contrary to this general trend,
      peptic ulcers are on the rise in the elderly, particularly elderly females. Two
      important factors that could explain the observed changes in the trends of peptic
      ulcer disease are: Helicobacter pylori and NSAID. The seroprevalence of H.
      pylori, determined in three previous studies, would appear to have decreased over
      the last few decades, while NSAID and aspirin are used increasingly for
      arthritis, cerebrovascular disease and coronary artery disease. The major
      complication of peptic ulcer disease is gastrointestinal haemorrhage and in the
      1990s endoscopic haemostatic therapy has replaced surgery as the treatment of
      choice. Treatment of peptic ulcer disease caused by H. pylori is directed at
      eradication of H. pylori itself; four classes of drug regimens are currently
      available for this. Antibiotic resistance, particularly metronidazole resistance,
      is an important factor that determines the outcome of therapy. Metronidazole
      resistance is reported to be present in 50% of all strains of H. pylori in Hong
      Kong and Singapore, and is present in 80-90% of all strains in India. Eradication
      rates in Asia, may for this reason, differ from those in the West, if the regimen
      contains metronidazole. Treatment of NSAID-associated ulcer consists of
      discontinuation of NSAID, if possible, and administration of anti-secretory drugs
      such as H2 blockers, proton pump inhibitors or mucosal protective agents. Co
      prescription with misoprostol has been shown to reduce the risk of NSAID-induced
      ulcer. New NSAID or NO NSAID are being developed with few gastrointestinal side
      effects.

PMID- 9195409
TI  - Prevalence of and risk factors for Helicobacter pylori infection in a multi
      racial dyspeptic Malaysian population undergoing endoscopy.
AB  - The aim of the present study was to determine the risk factors for Helicobacter
      pylori in a dyspeptic Malaysian population. A cross-sectional survey of 1060
      consecutive patients presenting with dyspepsia at the Endoscopic Unit, University
      Hospital, Kuala Lumpur, Malaysia from January 1994 to July 1995 was undertaken.
      All patients answered a detailed questionnaire and underwent endoscopy, with two
      antral biopsies taken for diagnosis of H. pylori using a rapid urease test. An
      overall H. pylori prevalence of 49.0% was recorded. Helicobacter pylori
      prevalence in relation to the major endoscopic diagnoses were as follows: non
      ulcer dyspepsia (NUD) 31.2%; duodenal ulcer (DU) 91.4%; and gastric ulcer (GU)
      74.1%. The prevalence among the races were as follows: Malay 16.4%; Chinese
      48.5%; and Indians 61.8%. Multiple logistic regression analysis identified the
      following as independent risk factors: > 45 years old 1.5 (1.1,2.0); male gender
      1.6 (1.2,2.1); ethnic group: Chinese 2.5 (1.7,3.7); Indians 4.9 (3.2,7.5); level
      of education: low 2.3 (1.5,3.5); middle 1.7 (1.1,2.6); and smoking 1.6 (1.2,2.3).
      Analysis was also performed on DU, GU and non-UD patients separately; in both DU
      and GU patients, H. pylori prevalence was high regardless of age, sex, race or
      level of education. However, in DU patients, Indian race had an independent risk
      factor (Odds ratio = 7.8 (1.2,48.4)). The findings in the NUD group reflected the
      findings in the ?all patients' group; > 45 years old, male gender, Indian and
      Chinese race, and low level of education were also significant, independent risk
      factors. The overall differences in H. pylori prevalence between the different
      subgroups were mainly due to differences in the NUD group. The increased risk of
      H. pylori infection in Chinese and Indians points to either an inherent ethnic
      genetic predisposition or to socio-cultural practices peculiar to the particular
      race which may be responsible for transmission of the infection.

PMID- 9195411
TI  - How to apply modern scientific and technological advances to the practice of
      clinical gastroenterology in Vietnam.
AB  - There are some differences between the spectrum of gastroenterological diseases
      in Vietnam compared with those of more developed countries. These may be due to
      different living standards, quality of nutrition, and different infection rates
      of intestinal parasites and hepatotropic viruses. Gastric carcinoma and
      hepatocellular carcinoma (HCC) are leading malignancies, while colorectal cancer
      is less frequent. Bile duct stones often have Ascaris eggs in the centre, and
      they prevail in incidence over gall-bladder stones. The majority of digestive
      cancers are detected at a very late stage. The Vietnamese Association of
      Gastroenterology aims to contribute to the development of modern gastroenterology
      (GE) in Vietnam, to study and apply recent advances in imaging technology, such
      as fibre-optic diagnostic and therapeutical endoscopy, ultrasonography,
      laparoscopic surgery etc. and to do further work in molecular biology. For this
      purpose, besides our self-reliance, we need, and ask for, support and assistance
      from the Japanese Society of GE (JSGE), the Asian Pacific Association of GE
      (APAGE) and the Organisation Mondiale de GE (OMEGE). At the same time, we suggest
      a choice be made among the different technologies, bearing in mind their cost
      effectiveness, and to give preference to measures for the primary prevention and
      early detection of the diseases. Japanese experience in the early detection of
      gastric cancer and HCC, and in the Percutaneous Ethanol Injection Therapy (PEIT)
      for treatment of HCC, are highly appreciated. We recommend also a judicious and
      scientific combination of traditional medicine and modern technology in the
      research and the struggle against digestive diseases.

PMID- 9195410
TI  - Viral hepatitis in Japan: update.
AB  - Viral hepatitis is defined as a hepatitis virus infection in which hepatic
      inflammation and necrosis lead to a characteristic feature. It is caused by at
      least five viral agents with specific epidemiological attributes and distinctive
      immunoserologic findings. The well-characterized forms are hepatitis A, B, C, D
      and E viruses. Recent status and the current progress of viral hepatitis in Japan
      are discussed in the present article.

PMID- 9195412
TI  - Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in
      Bangladesh.
AB  - The relationship between tropical calcific pancreatitis (TCP) and fibrocalculus
      pancreatic diabetes (FCPD) is still unclear. The clinical, biochemical and
      radiological data of age-matched TCP and FCPD subjects have been briefly
      discussed in the present review. Fibrocalculus pancreatic diabetes patients
      present with a significantly lower BMI compared with TCP patients. Analysis of
      the family history reveals that some kind of environmental factors seem to play a
      predominant role in the development of diabetes in FCPD patients, although these
      factors remain to be identified. Both TCP and FCPD patients predominantly come
      from a rural background. Fasting and 2 h blood glucose values as well as
      fructosamine levels in FCPD patients are approximately four-times higher than
      those of TCP patients. Measurements of early renal haemodynamic and microvascular
      changes (glomerular filtration rate, kidney size, microalbuminuria and
      microtransferrinuria) indicate an early renal involvement in FCPD patients.
      Tropical calcific pancreatitis subjects have approximately twice as high fasting
      C-peptide values compared with FCPD patients. Findings of single stranded DNA
      measurements suggest the involvement of oxidative damage in FCPD patients.
      Ketosis resistance is the most conspicuous clinical feature in the FCPD group and
      this relative absence of ketosis is probably due to a defect in the ketone body
      synthesis pathway and/or in the regulation of counterbalancing hormones.
      Endoscopic retrograde pancreatography findings of TCP and FCPD patients suggest
      that FCPD should not be considered only as a form of secondary diabetes
      consequent to generalized pancreatic damage in TCP.

PMID- 9195413
TI  - Presidential address: from where we stand.

PMID- 9195414
TI  - Biomechanical effects of operative nerve mobilization and transposition in a
      canine ulnar nerve model.
AB  - The purpose of this study was to evaluate the effects that operative mobilization
      and transposition of the ulnar nerve have on both neural excursion and mechanical
      properties. Twelve dogs underwent ulnar nerve transposition and postoperative
      casting. Four animals were killed at 3 weeks and four animals were killed at 6
      weeks. Four animals had their casts removed at 3 weeks, were allowed to ambulate,
      and were killed at 6 weeks. Operated and contralateral control nerves were
      compared. Neural excursion was measured near the elbow and 12 cm proximally. The
      nerves were harvested and their mechanical properties determined. Repeated
      measures analysis of variance revealed significant differences in longitudinal
      excursion between control and experimental groups at both sites. Ultimate strain,
      ultimate strength, and modulus were significantly reduced in the experimental
      groups. No differences were seen in cross-sectional area or stiffness between
      control and experimental groups. Analysis revealed no independent effect of the
      rehabilitation method. Results of this study indicate that significant changes in
      neural excursion, ultimate strain, ultimate strength, and modulus occur following
      ulnar nerve mobilization and transposition and that these changes persist
      throughout the early postoperative period.

PMID- 9195415
TI  - Long-term symptom outcomes of carpal tunnel syndrome and its treatment.
AB  - A retrospective follow-up study of a population-based case series was conducted
      to determine the clinical course and outcomes of carpal tunnel syndrome (CTS). A
      total of 425 cases first diagnosed between 1979 and 1988 were followed through
      1993. Among patients who did not have surgery, median duration of symptoms was
      between 6 and 9 months, but 22% had symptoms for 8 years or longer. Patients who
      had surgery were about 6 times more likely to have resolution of their symptoms
      than were patients who did not have surgery. Patients who had surgery 3 or more
      years after their initial diagnosis of CTS were less than half as likely to have
      symptom resolution than were patients who had surgery within 3 years of
      diagnosis. The results indicate that surgery is a highly effective treatment, but
      duration of CTS prior to surgery is a key determinant of surgical outcome.

PMID- 9195416
TI  - A case-control study of obesity as a risk factor for carpal tunnel syndrome in a
      population of 600 patients presenting for independent medical examination.
AB  - Pain, numbness, and tingling through the median nerve distribution, known as
      carpal tunnel syndrome (CTS), has been associated with many personal risk
      factors. Previous studies have implicated obesity as a risk factor for median
      neuropathy at the carpal tunnel. A case-control design was undertaken to explore
      the association between obesity and CTS. Six hundred patients presented with
      symptoms of upper-extremity disorders for independent medical examination related
      to a disability or compensation claim. The 300 patients with electrodiagnostic
      evidence of CTS were compared with 300 control subjects from the same initial
      population. All patients were categorized according to their body mass index. The
      analysis was stratified for the possible confounding factors of cervical spine
      abnormalities, Martin-Gruber interconnections, age, and sex. A statistically
      significant association was found between obesity and median neuropathy. The
      implications of such a relationship are discussed in light of the contemporary
      debate over the etiology of cumulative trauma disorders.

PMID- 9195417
TI  - Relation of preoperative nerve-conduction values to outcome in workers with
      surgically treated carpal tunnel syndrome.
AB  - Ninety-three workers having undergone carpal tunnel decompression were assessed
      16 to 100 months after surgery. The results of outcomes pertaining to symptoms of
      numbness, nocturnal awakening, and pain as well as job status were compared to
      the patients' preoperative nerve conduction study findings. Significant
      differences in preoperative nerve-conduction values (NCVs) were found between
      groups reporting poor results and those reporting good results. These differences
      were such that those reporting poor results had more normal NCVs. Those reporting
      job changes because of carpal tunnel syndrome also had more normal preoperative
      nerve-conduction results. Data indicate that those with terminal latencies 1 ms
      greater than the testing facility normal value or with sensory conduction
      velocity 10 ms less than the facility norm were more likely to benefit from
      surgery. This study suggests the need for caution when considering carpal tunnel
      surgery in workers with normal or near normal nerve-conduction results.

PMID- 9195418
TI  - Assessment of the carpal tunnel outcome instrument in patients with nerve
      compression symptoms.
AB  - The outcome movement in medicine has encouraged the development of patient
      answered questionnaires as measures of well-being. A disease-specific
      questionnaire for carpal tunnel syndrome (CTS) was introduced by Levine et al. in
      1993. We evaluated this questionnaire in 156 consecutive new patients presenting
      with pain, numbness, or tingling of the upper extremity. Of these, 114 correctly
      filled out the carpal tunnel outcome instrument. In addition, these patients
      completed the self-administered hand diagram developed by Katz and Stirrat for
      the diagnosis of CTS. The 114 patients were classified according to their hand
      diagram as classic or probable CTS (n = 47), possible CTS (n = 31), and unlikely
      CTS (n = 36). The mean symptom severity score in patients classified as classic
      or probable CTS was significantly higher than the mean score in patients
      classified as possible or unlikely CTS (p < .01). The mean scores of items
      regarding sensory symptoms were significantly higher in patients with classic or
      probable CTS compared to patients with possible or unlikely CTS (p < .0001). The
      scores were similar for CTS and non-CTS patients on the functional status
      subscale.

PMID- 9195419
TI  - Patterns of median nerve sensory innervation to the thumb and index finger: an
      anatomic study.
AB  - Anatomic dissections were performed on 79 cadaveric hands to elucidate the
      patterns of median nerve sensory innervation to the thumb and index finger. The
      most common pattern (type I, 69%) consisted of a radial digital nerve to the
      thumb and a common digital nerve to the first web, which subsequently divided
      into a radial digital nerve to the index and an ulnar digital nerve to the thumb.
      The least common (type II, 6%) consisted of a common digital nerve to the thumb
      and a proper digital nerve to the radial side of the index finger. A trifurcation
      pattern (type III, 25%) consisted of three proper digital nerves (radial thumb,
      ulnar thumb, and radial index). These findings are at odds with most standard
      textbook descriptions, which depict types II and III most frequently.

PMID- 9195420
TI  - Anatomy of the radial nerve motor branches in the forearm.
AB  - Knowledge of radial nerve motor branch anatomy is important when performing
      surgery in its vicinity, neurorrhaphy, and nerve blocks and for understanding the
      rate and order of recovery of muscle function after injury. Twenty normal fresh
      cadaver arms were dissected to quantitate radial nerve motor branch anatomy in
      the forearm. Though variable in individual specimens, innervation order from
      proximal to distal (based on mean shortest branch lengths) was brachioradialis,
      extensor carpi radialis longus, supinator, extensor carpi radialis brevis,
      extensor digitorum communis, extensor carpi ulnaris, extensor digiti quinti,
      abductor policis longus, extensor policis longus, extensor policis brevis, and
      extensor indicis proprius. In 10 specimens, branches innervated the branchialis.
      Mean distances from a point 100 mm proximal to the lateral epicondyle to the
      muscle measured along the shortest nerve branch ranged from 97.2 mm for the
      brachioradialis to 299.8 mm for the EIP. The mean number of muscular branches
      ranged from 1.1 in the EIP to 4.6 in the EDC. Mean nerve length from the radial
      styloid to the last motor branch was 115.8 mm.

PMID- 9195421
TI  - Treatment of unstable distal radius fractures: methods and comparison of external
      distraction and ORIF versus external distraction-ORIF neutralization.
AB  - Twenty-six closed unstable distal radius fractures were treated using a
      combination of internal fixation, external distraction (intraoperative), and, in
      some cases, up to 4 weeks of postoperative external fixation (neutralization).
      Intraoperative stability check determined the need for external neutralization.
      This combined technique allowed a comprehensive approach to even the most
      unstable fracture by merging the advantages of internal and external fixation. Up
      to 4 weeks of external fixation (neutralization) was not associated with the
      complications of external fixation usually reported.

PMID- 9195422
TI  - Percutaneous pinning of distal radius fractures: a biomechanical study.
AB  - Mechanical testing of extra-articular distal radius fractures stabilized with
      percutaneous pins was performed. Twelve fresh-frozen unembalmed radii stripped of
      all soft tissues were used. An osteotomy with dorsal comminution was made 2.5 cm
      proximal to the radial styloid. Three pin sizes and four pin configurations were
      used to fix the fracture, and the constructs were mechanically tested. Results
      show that at least a .062-inch pin was required for any significant changes in
      rigidity of the four pin configurations tested to be discerned. Cross-pinning
      with two radial styloid pins and placement of a pin from the ulnar corner of the
      radius as the most rigid construct in both torsion and cantilever bending.

PMID- 9195423
TI  - The effects of distal radius fracture malalignment on forearm rotation: a
      cadaveric study.
AB  - Seven fresh cadaveric specimens were used to determine the loss of forearm
      rotation with varying distal radius fracture malalignment patterns. Uniplanar
      malunion patterns consisting of dorsal tilt, radioulnar translation, or radial
      shortening were simulated by creating an osteotomy at the distal end of the
      radius, orienting the distal fragment position using an external fixator, and
      maintaining the position with wedges and a T-plate. Rotation of the forearm was
      produced by fixing the elbow in a flexed position and applying a constant torque
      to the forearm using deadweights. Forearm rotation was measured with a
      protractor. Dorsal tilt to 30 degrees and radial translation to 10 mm led to no
      significant restriction in forearm pronation or supination ranges of motion. A 5
      mm ulnar translation deformity resulted in a mean 23% loss of pronation range of
      motion. Radial shortening of 10 mm reduced forearm pronation by 47% and
      supination by 29%.

PMID- 9195424
TI  - Rupture of all finger flexor tendons 17 years after a colles fracture: a case
      report.
AB  - A case with closed sequentional rupture of all flexor tendons of the fingers, 17
      years after a Colles fracture is described. The repair with free tendon grafts
      resulted in a fair result.

PMID- 9195425
TI  - Compartment syndrome of the pronator quadratus: a case report.
AB  - A case of compartment syndrome involving the pronator quadratus following a
      severe crush injury is presented. The theoretic criteria for evaluating this
      compartment during fasciotomy are discussed.

PMID- 9195426
TI  - The use of frozen-allograft radial head replacement for treatment of established
      symptomatic proximal translation of the radius: preliminary experience in five
      cases.
AB  - Five patients with disabling symptoms related to proximal translation (> 1 cm) of
      the radius following radial head excision (Essex-Lopresti lesion) were treated
      with implantation of a frozen-allograft radial head prosthesis. Following
      restoration of neutral ulnar variance at the wrist, a size-matched frozen radial
      head allograft was implanted and secured to the proximal radius with internal
      fixation. In three patients, this was a two-stage procedure; radial length was
      restored gradually using an ilizarov external fixation device and the allograft
      was placed later. Patients were evaluated clinically and radiographically at a
      mean follow-up time of 3 years (range, 1-7 years). All patients had relief of
      wrist and elbow pain and were satisfied with the outcome of the operation.
      Forearm rotation improved by a mean of 37 degrees and wrist motion improved by a
      mean of 45 degrees. Forearm reconstruction with frozen radial head allograft
      implantation may be a beneficial method of treatment for this difficult problem.

PMID- 9195427
TI  - Synovectomy, radial head excision, and anterior capsular release in stage III
      inflammatory arthritis of the elbow.
AB  - A retrospective study was performed to analyze the results of elbow synovectomy,
      radial head excision, and anterior capsular release in 12 elbows in 11 patients
      with radiographic stage III inflammatory arthritis. The follow-up period averaged
      6.1 years. Average flexion arc improved from 93 degrees (range, 80 degrees-110
      degrees) to 116 degrees (range, 65 degrees-140 degrees), with flexion contracture
      improving 13 degrees. Total arc of forearm rotation increased from 95 degrees to
      145 degrees. Ewald scores improved from an average of 37 to 84 points. Pain was
      eliminated or improved in all cases; functional improvement was noted in all
      patients. Serial postoperative radiographs showed no significant disease
      progression over time. These results suggest that combined synovectomy, radial
      head excision, and anterior capsular release effectively relieves pain and
      improves function in stage III inflammatory arthritis of the elbow.

PMID- 9195428
TI  - Development of a surface replacement arthroplasty for proximal interphalangeal
      joints.
AB  - Sixty-six surface replacement proximal interphalangeal prostheses with a CrCo
      proximal and an ultrahigh-molecular-weight polyethylene distal component were
      used in the hands of 47 patients (mean age, 58 years) over a 14-year period.
      There were 37 fingers with degenerative arthrosis, 16 with traumatic arthrosis,
      and 13 with rheumatoid arthritis. The mean follow-up period was 4.5 years (range,
      1-14 years). The results based on pain relief, motion, and deformity were good in
      32 fingers, fair in 19, and poor in 15. Poor results occurred primarily in
      fingers with previous extensive injury or static deformity. Results with a dorsal
      approach were better than those with a lateral or palmar approach. Component
      loosening at the bone-cement junction beyond a minimal radiolucent line was seen
      in one late x-ray. Results in individuals changed little after the first year of
      follow-up care, but results overall improved during the course of the study,
      perhaps because of improvements in surgical technique and experience.

PMID- 9195429
TI  - Pre- and postimplantation dynamic mechanical properties of silastic HP-100 finger
      joints.
AB  - Dynamic mechanical properties of Silastic HP-100 finger joint implants were
      studied. Sixteen sections of unimplanted and 14 sections of retrieved implants
      were analyzed with standard thermal analysis techniques. Results show that
      implantation does not alter the viscoelastic properties of Silastic HP-100
      elastomers. The authors conclude that fracture of Silastic HP-100 implants cannot
      be attributed to changes in rheologic properties of the implanted elastomer.

PMID- 9195430
TI  - Major vascular malformations of the upper extremity: long-term observation.
AB  - Vascular malformations of the upper extremity continue to be a therapeutic
      challenge to the hand surgeon. In the past 22 years, the authors treated 17
      patients with major vascular malformations of the upper extremity. The lesions
      were evaluated with the aid of plain radiographs, angiography, and histology.
      Thirteen of the patients were female and 4 were male. The average age at
      treatment was 18 years, ranging from birth to 64 years. The average follow-up
      period was 12 years, ranging from 4 months to 36 years. The main indications for
      surgery were pain, progressive enlargement, neurologic compromise, diminished
      function, or a combination of these. The progression of these lesions under
      observation led to surgical management in all cases. A total of 36 excisions, 3
      embolizations, and 4 amputations were done. Postoperative angiograms were
      obtained in selected individuals. Diffuse lesions defied total surgical removal.
      Recurrence and persistence was evident in 12 of the 17 patients. A knowledge of
      the progressive nature of these lesions and the need for long-term observation
      are the keystones to the successful management of these challenging yet
      unresolved problems.

PMID- 9195431
TI  - A new approach to the reverse dorsal metacarpal artery flap.
AB  - The distally based dorsal hand flap on the recurrent cutaneous branch was
      dissected as a reverse flap based on the connection between the dorsal branch of
      the proper digital artery and the terminal branches of the dorsal metacarpal
      artery at the level of the proximal phalanx. The reverse dorsal metacarpal artery
      flap dissected by this new approach was applied in five cases for coverage of
      some areas in the fingers. Two flaps were raised on the second and three on the
      third intermetacarpal space. All flaps survived completely. The donor areas were
      closed by direct approximation.

PMID- 9195432
TI  - Aneurysms of the digital arteries: a case report and literature review.
AB  - Aneurysms of the digital vessels are rare. An aneurysm of the radial digital
      artery of the index finger in a child is reported to illustrate the clinical
      presentation and value of magnetic resonance arteriography in diagnosis.
      Literature review reveals that only 18 cases have been reported. These cases are
      analyzed in terms of digit involvement, vessel affected, mechanism of injury, and
      treatment.

PMID- 9195433
TI  - Two-stage reconstruction of apert acrosyndactyly.
AB  - This report retrospectively reviews presenting radiographs and surgical treatment
      of 28 hands in 14 children with Apert acrosyndactyly with the purpose of
      developing a classification system to describe the decision-making process used
      to determine the type and staging of hand reconstruction. The average patient age
      at last follow-up evaluation was 7 years (range, 3-17 years). Type I deformities
      (7 hands) had little or no angular deformity at the metacarpophalangeal (MP)
      joint; two-stage reconstruction created a four-fingered hand. Type IIA
      deformities (11 hands) had mild MP joint angular deformity and a more proximal
      complex syndactyly of the middle three digits; two-stage reconstruction created a
      three-fingered hand with ray resection of the third digit. Type IIB deformities
      (7 hands) had pronation of digit 2 superimposed on the thumb and radial
      angulation at the MP joint of digit 2; two-stage reconstruction created a three
      fingered hand with ray resection of the second digit. Type IIC deformities (3
      hands) had supination of digit 4 superimposed on digit 5 with ulnar angulation at
      the MP joint of digits 4 and 5; two-stage reconstruction created a three-fingered
      hand with ray resection of the fourth digit. This report presents a
      classification system and four different treatment strategies based on presenting
      radiographs.

PMID- 9195434
TI  - Staged flexor tendon reconstruction using pedicled tendon graft from the flexor
      digitorum superficialis.
AB  - The use of pedicled flexor digitorum superficialis tendon as a tendon graft in
      the second stage of flexor tendon reconstruction has the advantage of employing
      local intrasynovial tendon graft and allowing early active range of motion. This
      method of staged flexor tendon reconstruction was used in 47 patients between
      1983 and 1993. Thirty-three patients were evaluated 1 year or longer after the
      second stage of surgery. The follow-up period averaged 3.7 years. Sixty-four
      percent of the injuries were in zone II, and 30% were Boyes grade V in severity.
      Good to excellent results were achieved in 64% of patients. Three patients needed
      graft tenolysis. Postoperative persistent flexion contractures ranging from 8
      degrees to 55 degrees of the proximal interphalangeal or distal interphalangeal
      joints or both were present in 88% of patients. Several factors that influenced
      the final outcome were identified: age over 25 years, zone II injuries of Boyes
      grade V, and the lack of a regular postoperative rehabilitation program were
      associated with relatively less successful final results.

PMID- 9195435
TI  - A biomechanical study of the flexor digitorum superficialis: effects of digital
      pulley excision and loss of the flexor digitorum profundus.
AB  - Many reports have been devoted to characterizing the significance of the pulleys
      for the flexor digitorum profundus (FDP). However, no comparable work has been
      published on the flexor digitorum superficialis (FDS). This study characterized
      the FDS in a human cadaver model. Eleven fresh-frozen cadaver hands were used. By
      using a tensiometer, data were gathered for tendon excursion, tendon load, and
      work of flexion. Changes in efficiency were caused by excision of annular pulleys
      A1, A2, A3, and the palmar aponeurotic pulley. We also measured the effect of FDP
      excision on FDS efficiency. Sectioning of the A2 and A3 pulleys together caused
      statistically significant losses of efficiency in all three parameters (work,
      load, and excursion). When the FDP was removed from a finger with an intact
      pulley system, losses in both work and excursion efficiencies were significant.
      Removing the FDP while cutting different pulleys caused significant decrease in
      FDS excursion efficiency. We conclude that A2 and A3 are the most important
      pulleys for maintaining normal FDS function, and that the presence of the FDP in
      the digital sheath is essential for optimal FDS excursion efficiency.

PMID- 9195436
TI  - Sarcoid flexor tenosynovitis of the wrist: a case report.
AB  - A case is presented where flexor tenosynovitis of the volar wrist is the
      presenting symptom of sarcoidosis in a 69-year-old man.

PMID- 9195437
TI  - Flexor tenosynovitis in the hand caused by Mycobacterium malmoense: a case
      report.
AB  - This report analyzes a rare case of flexor tenosynovitis caused by Mycobacterium
      malmoense. A synovectomy was carried out on the index finger (no other finger was
      afflicted) of a 66-year-old farmer, followed by antibiotic therapy with
      ethambutol, rifampin, and clarithromycin. Because of strong side effects, the
      treatment with ethambutol and rifampicin had to be discontinued after 4 months.
      There was no recurrence after 14 months, and the patient's finger had a full
      range of motion.

PMID- 9195438
TI  - Rupture of the triceps muscle at the musculotendinous junction: a case report.
AB  - Rupture of the triceps brachii at the musculotendinous junction is reported in a
      patient with diabetes mellitus and hypertension. Successful reconstruction was
      achieved by delayed primary repair. V-Y advancement of the triceps, and a
      plantaris tendon graft.

PMID- 9195439
TI  - Arthroscopic debridement alone for intercarpal ligament tears.
AB  - This study examined the role of arthroscopic debridement alone for complete and
      incomplete intercarpal ligament tears of the wrist. Forty-three wrists underwent
      arthroscopic evaluation for persistent wrist pain and were identified as having
      isolated scapholunate or lunotriquetral ligament tears treated by arthroscopic
      debridement alone of the torn ligament edges. At follow-up examination at an
      average of 27 months, 29 (66%) wrists having a complete scapholunate ligament
      tear and 36 (85%) wrists having a limited scapholunate ligament tear had either
      complete symptom resolution or improved symptomatology. Thirty-three (78%) wrists
      with a complete lunotriquetral ligament tear and 43 (100%) wrists having a
      limited lunotriquetral ligament tear had complete symptom resolution or
      improvement. No wrists were noted to have static intercarpal instability pattern
      changes on follow-up radiographs. Grip strength improved 23% postoperatively.
      These findings suggest that intercarpal ligament tears, in a majority of
      patients, may be treated from a symptomatic standpoint by debridement alone for
      at least several years. The long-term ability of this approach to maintain a pain
      free wrist has yet to be determined. No statistically significant difference was
      noted in the symptomatic improvement rate of scapholunate compared to
      lunotriquetral ligament debridement.

PMID- 9195440
TI  - Tumoral calcinosis of the triangular fibrocartilage complex: a case report.
AB  - A case of calcium hydroxyapatite deposition in the triangular fibrocartilage of
      the wrist is presented. The deposit took the more unusual form of a tumor, posing
      diagnostic difficulties. Magnetic resonance imaging was helpful in delineating
      the lesion, but could not identify its nature. Surgical excision resulted in
      resolution of symptoms.

PMID- 9195441
TI  - Melanoma of the hand.
AB  - Melanomas of the hand are relatively rare, and much confusion exists concerning
      their pathology and treatment. We reviewed our experience with 39 patients
      diagnosed with melanoma of the hand. The data were categorized by site,
      histology, and type of treatment. Most primaries were on the digits, with a few
      tumors arising on the palm. The most common histology was superficial spreading
      melanoma, even in the subungual location. Acral lentiginous melanoma accounted
      for only 8 of 39 cases. Most patients could be treated without radical
      amputations, even for melanomas on the digits. Review of our patients emphasized
      the need for early diagnosis. Biopsy of all unexplained pigmented lesions on the
      hands can lead to early diagnosis, relatively nondeforming treatment, and good
      survival.

PMID- 9195442
TI  - Modified transthecal digital block.

PMID- 9195443
TI  - Lies, damn lies, and statistics.

PMID- 9195444
TI  - Statistical analysis as related to hand surgery.

PMID- 9195446
TI  - Trispiral tomographic staging of Kienbock's disease.
AB  - Trispiral tomography enhances the staging of Kienbock's disease and aids in
      surgical planning. The clinical records, plain x-rays, and trispiral tomograms of
      105 patients with Kienbock's disease were reviewed. When tomograms were used,
      upward revision of the classification stage was indicated in 73% of patients with
      stage I or stage II disease and in 10% of those with stage III disease. On
      tomograms, 91% of patients had lunate fractures, compared with 55% on plain
      films. The most common lunate fracture seen on trispiral tomograms was a
      transverse shear fracture that represented lunate collapse; the next most common
      was a midcoronal fracture that may be displaced, causing fragment extrusion
      palmarly or dorsally. The most common instability pattern was nondissociative
      proximal row flexion, seen in stage III. Indices of carpal collapse and ulnar
      translation may be useful in following up patients, but values vary widely among
      patients.

PMID- 9195445
TI  - Radial recession osteotomy for Kienbock's disease.
AB  - Sixty-eight patients underwent radial recession osteotomy for avascular necrosis
      of the lunate were retrospectively evaluated after an average follow-up period of
      52 months. Twenty-five patients had undergone 1 or more additional procedures
      concurrently for treatment of Kienbock's disease. Pain diminished in 93% of
      patients, grip strength improved, and wrist motion was preserved; 75% of patients
      continued in their original occupations, including heavy labor. Surgical
      complications were uncommon. Four patients subsequently underwent salvage
      procedures, including 2 total wrist arthrodeses. Three of these 4 patients were
      receiving workers' compensation. One third of patients demonstrated lunate
      healing after joint leveling. Preliminary results suggest that concomitant lunate
      revascularization or vascularized bone grafting may improve the radiographic
      result. With rare exceptions, radial recession osteotomy relieves pain and
      improves function in Kienbock's disease.

PMID- 9195447
TI  - Lunatomalacia associated with congenital shortening of the ulna in Langer-Giedion
      syndrome: a case report.
AB  - A 22-year-old patient with type I trichorinophalangeal Langer-Giedion syndrome
      presented a stage 2 osteonecrosis of the lunate associated with congenital
      shortening of the ulna and carpal tunnel syndrome. The patient was treated by
      shortening osteotomy of the radius and median nerve neurolysis, with an excellent
      result. This case provides an additional piece of evidence associating ulnar
      minus variance with lunatomalacia, and another argument in favor of the theory
      that Kienbock's disease results from microfractures sustained by the lunate under
      an abnormal stress distribution situation.

PMID- 9195448
TI  - A cadaveric anatomic study of radial artery pedicle grafts to the scaphoid and
      lunate.
AB  - This study was designed to determine the frequency of available radial styloid
      and metacarpal vascularized bone pedicle grafts and to determine the potential
      clinical availability (ie, sufficient length) of each pedicle graft for
      revascularization procedures to the dorsal and palmar scaphoid and dorsal lunate.
      Five vascularized bone pedicles (radial styloid 1, radial styloid 2, first
      metacarpal, second metacarpal, and third metacarpal) were evaluated in 20 fresh
      frozen unpaired cadaveric forearms after methylene blue injection. For the dorsal
      approach to the scaphoid, radial styloid 2 bone graft was most reliable; for a
      palmar approach to the scaphoid, the first metacarpal graft was the most
      reliable; and for the dorsal approach to the lunate, the third metacarpal was the
      most reliable. Not all pedicles were available in all specimens; thus,
      versatility in using all five pedicles is recommended.

PMID- 9195449
TI  - Repeat screw stabilization with bone grafting after a failed Herbert screw
      fixation for acute scaphoid fractures and nonunions.
AB  - Eight patients with persistent nonunions after failure of a Herbert screw
      fixation for both acute scaphoid fractures and nonunions underwent repeat screw
      internal fixation and bone grafting. They were followed for at least 1 year
      (average, 19 months) after their last surgical procedure. In 6 patients, union
      was achieved following the second surgery. These patients were pain free and
      resumed their previous occupations. The average range of wrist mobility was 87%
      of that of the uninvolved wrist, and grip strength averaged 93% of that of the
      uninvolved wrist. In 1 of the 2 patients with an unsuccessful outcome after the
      second procedure, union was achieved after a third procedure was performed that
      involved an inlay bone graft and internal fixation using a Kirschner wire. The
      remaining patient had relief of pain following denervation of the wrist joint.
      These 2 patients did not show marked clinical improvement and required a change
      of employment of light work. On the basis of study findings, it appears that
      revision with a repeat Herbert screw fixation and bone grafting is the treatment
      of choice for patients with persistent scaphoid nonunions following an
      unsuccessful Herbert screw procedure in which the screw is not correctly placed.

PMID- 9195450
TI  - Extensor carpi radialis longus tendon arthroplasty in the treatment of primary
      trapeziometacarpal arthrosis.
AB  - A prospective study was conducted to evaluate patient outcomes following
      trapezial excision and extensor carpi radialis longus tendon arthroplasty in
      primary trapeziometacarpal arthrosis. Seventeen patients were evaluated both
      preoperatively and postoperatively at both 12 months and at final follow-up
      examination at a mean of 39 months (range, 20-56 months). Surgery resulted in
      complete or significant pain relief and satisfaction with outcome for 16 patients
      as evaluated at final follow-up examination. Patients with a longer history of
      thumb pain and more advanced preoperative radiographic changes were more likely
      to have residual pain after surgery. The mean preoperative activities of daily
      living (ADL) scores improved significantly. The mean pulp and key pinch strength
      were 93% and 100%, respectively, of the preoperative values but were
      significantly lower than the mean pinch strengths recorded in an age-matched
      control population. Substantial proximal migration of the first metacarpal during
      maximal pinch was noted in 4 patients who still had some degree of thumb pain
      with light work. Scaphotrapezoid arthrosis had no correlation to postoperative
      residual pain.

PMID- 9195451
TI  - Intra-articular fractures of the distal end of the radius treated with an
      adjustable fixator system.
AB  - Twenty-five wrists with comminuted, displaced, intra-articular fractures of the
      distal radius were prospectively treated with an adjustable external fixator for
      an average of 51 days. Twenty fractures (80% [20 of 25] were available for follow
      up) in 16 adults (mean age, 34 years) were treated with the Wrist Jack external
      fixator system (Hand Biomechanics Lab, Sacramento, CA) and evaluated at a mean
      follow-up period of 25 months. Ten patients (12 fractures) sustained high-energy
      trauma with multiple injuries, while 6 patients (8 fractures) sustained isolated
      distal radius fractures. Percutaneous pins supplemented the fixation in 6
      fractures. All fractures were reduced to restore articular congruity to within 1
      mm. At follow-up, 5% were excellent, 75% good, 20% fair, and none as poor using
      the demerit point system of Gartland and Werley as modified by Sarmiento. Grip
      strength averaged 80% of the unaffected limb. Seventeen of the 20 fractures
      showed some evidence of articular incongruity at follow-up evaluation.
      Restoration of palmar tilt, radial inclination, radial length, and range of
      motion were at acceptable values. Subjective analysis confirmed 85% of the
      patients to have only occasional pain or none at all and 15% to have some pain
      with weakness or limitation of motion. Two patients required additional surgery:
      1 underwent a Darrach procedure and the other a tendon transfer for a rupture of
      the extensor pollicis longus tendon. Results suggest that an external fixator
      system provides an additional alternative to the surgical armamentarium for an
      otherwise difficult fracture fixation problem.

PMID- 9195452
TI  - Correction of malunited Bennett's fracture by intra-articular osteotomy: a report
      of two cases.
AB  - Two young male laborers had a corrective intra-articular osteotomy for a
      symptomatic malunited Bennett's fracture. Follow-up examination at 24 and 40
      months, both patients experienced dramatic pain relief and improved thumb range
      of motion, and grip, and pinch strengths. A corrective intraarticular osteotomy
      is an acceptable alternative to arthrodesis or arthroplasy in select patients
      with a malunited Bennett's fracture.

PMID- 9195453
TI  - Simplified functional splinting after extensor tenorrhaphy.
AB  - The medical records of 22 patients who had a total of 61 simple or complex
      lacerations of finger, thumb, and wrist extensor tendons repaired in zones V-VIII
      (thumb zones TIII-TV) were reviewed. By 7 days after surgery, custom-molded
      splints were applied to hold the patients' wrists extended (approximately 30
      degrees) and the metacarpophalangeal (MP) joints flexed slightly (20 degrees-30
      degrees), leaving the interphalangeal (IP) joints free. If thumb tenorrhaphies
      were done, the thumb carpometacarpal and MP joints were included and splinted in
      neutral (0 degree extension) position. Patients performed active JP joint range
      of motion (ROM) exercises as instructed. At a mean follow-up period of 4.5 months
      (range, 1.5-12 months), there were no residual impairments that interfered with
      patients' activities of daily living or prevented their return to preinjury
      employment status; 19 of 22 patients (86%) had good or excellent results, based
      on objective criteria of active motion. There were no tenorrhaphy failures. The
      results support the concept of functional splinting techniques, which allow early
      active IP joint ROM while protecting the repaired tendons, thus resulting in less
      joint stiffness than older methods of static splinting without being as
      complicated and labor-intensive as dynamic splinting.

PMID- 9195454
TI  - Sagittal band reconstruction.
AB  - Extensor tendon subluxation at the metacarpophalangeal joint occurs only rarely
      in patients without rheumatoid arthritis. Almost all reported cases involve
      disruption of the radial sagittal band with ulnar subluxation of the extensor
      tendon. A technique of sagittal band reconstruction is described that entails
      weaving a retrograde segment of extensor tendon upon itself after passing it
      through the deep transverse metacarpal ligament. Twenty-one sagittal band
      reconstructions were performed in 16 patients. This series included 18 cases of
      ulnar subluxation secondary to radial sagittal band disruption and 3 cases of
      radial subluxation secondary to ulnar sagittal band disruption. Using this
      technique, pain was eliminated in every case and there has been no recurrence of
      extensor tendon subluxation.

PMID- 9195455
TI  - Tensile properties of canine intrasynovial and extrasynovial flexor tendon
      autografts.
AB  - This study compared the biomechanical properties of intrasynovial and
      extrasynovial flexor tendon autografts in an adult canine model. Flexor digitorum
      profundus (FDP) tissue from the fifth toe of the hindpaw was harvested and
      transplanted as an intrasynovial graft to the second toe of the left forepaw of
      each animal. Peroneus longus tendon from the lateral compartment of the hind leg
      served as the source for the extrasynovial graft that was transplanted to the
      fifth toe of each dog's left forepaw. The second and fifth FDP tendons of the
      right forepaw constituted the respective contralateral controls. Postoperatively,
      each animal underwent a regimen of daily controlled passive mobilization. Three
      and 6 weeks after grafting, 6 animals were euthanized and their grafts evaluated
      for gliding function and tensile properties. Results reveal significantly greater
      angular rotation of the proximal interphalangeal joint in the digits that
      received intrasynovial grafts relative to those that received transplanted
      extrasynovial tendon at both 3 and 6 weeks postoperatively. The linear stiffness
      of the tendons receiving extrasynovial graft significantly exceeded that of the
      intrasynovial group. These findings correlated with histologic data that
      postoperative adhesions existed in the specimens with an extrasynovial graft. In
      addition, the extrasynovial tendon graft complex exhibited significantly higher
      ultimate loads than intrasynovial tendon graft complex at 6 weeks.

PMID- 9195456
TI  - Effect of immobilization, immediate mobilization, and delayed mobilization on the
      resistance to digital flexion using a tendon injury model.
AB  - This study employed a tendon injury model in chickens to determine the effect of
      immobilization, immediate mobilization, and delayed mobilization on the energy
      required to fully flex the digit following surgical trauma to the tendon, as
      determined by measurement of the work of flexion (WOF). The immobilized group
      showed no increased WOF at 3 days compared to the zero time control values,
      followed by significant increased WOF at 1 week (36%), 2 weeks (41%), and 3 weeks
      (63%). The immediate mobilization tendons showed an initial 36% rise in the work
      of flexion at 3 days, which increased to 40% at 1 week, and then decreased to
      baseline control values by 3 weeks. Delaying the period of mobilization until 5
      days was not shown to significantly lower the peak WOF value at 1 week, but
      delaying the period of mobilization until 3 days lowered the peak WOF value at 1
      week dramatically to 13%; both the 3- and 5-day delayed-mobilization groups
      returned to baseline WOF values by 3 weeks. From these data, it can be assumed
      that there is an early increase in the work necessary for flexion of the injured
      operated digit and tendon that is present in the immediately mobilized tendons at
      3 days and persists to 1 week and that does not appear until 1 week in the
      immobilized tendons; this rise in WOF can be blunted by delaying the institution
      of mobilization.

PMID- 9195457
TI  - Ligamentomuscular protective reflex in the elbow.
AB  - A reflex are from the medial elbow ligaments to the forearm pronator muscles was
      shown to exist in the feline model. A single articular branch emerging from the
      median nerve and converging on the medial collateral ligament was identified and
      stimulated with supramaximal pulses of 100 microseconds duration at a rate of 10
      pulses/s. Stimulation of the articular nerve elicited myoelectric activity in the
      flexor digitorum superficialis, flexor digitorum profundus, flexor carpi
      radialis, flexor carpi ulnaris, and pronator teres. Transection of the articular
      nerve between the electrodes and the median nerve resulted in the disappearance
      of any myoelectric activity in the muscles, thus confirming the afferent nature
      of the articular nerve. The mean time delay from the application of the stimulus
      to the corresponding myoelectric discharge ranged from 3.2 to 5.8 ms for the 5
      muscles. The existence of a fast-acting reflex arc from the medial elbow
      ligaments to the forearm muscles both confirms the concept of ligamentomuscular
      protective synergy (shown to exist in the knee, shoulder, and ankle joints) and
      extends it to the elbow. This reflex arc has significant implications for both
      the planning of elbow surgery while preserving the neural supply of the ligaments
      and for the planning of postsurgical or conservative therapeutic rehabilitation
      modalities.

PMID- 9195458
TI  - Classification of ulnar deficiency according to the thumb and first web.
AB  - Fifty-five ulnar-deficient upper extremities in 45 patients treated at the St.
      Louis Shriner's Hospital were reviewed in order to evaluate the hand
      abnormalities. Thumb and first-web abnormalities were noted in 73% of hands. The
      majority of operations (28 of 53) were recommended to improve functional deficits
      associated with abnormalities of the thumb and first web. A classification of the
      ulnar-deficient hand based upon the characteristics of the thumb and first web is
      presented. When used in combination with any of the six current forearm/elbow
      classification schemes, this classification more completely describes ulnar
      deficiency of the upper extremity. Four classification types are proposed based
      upon progressive involvement of the thumb and first web. In type A, the thumb and
      first web are normal; in type B, the first web space has mild deficiency and the
      thumb has mild involvement. Extrinsic tendon function is intact and opposition
      function is present. In type C, the thumb has varying degrees of involvement. The
      first web has moderate to severe deficiency, including thumb-index syndactyly,
      and is often associated with malrotation of the thumb into the plane of the other
      digits, loss of opposition, and dysfunction of the extrinsic tendons. In type D,
      the thumb is absent. Previous classifications of ulnar deficiency neglect the
      radial hand anomalies that have been noted by several authors in a high
      percentage of affected extremities. Our premise for this classification is that
      the thumb and first-web abnormalities are related to the complexity of the hand
      problem and that the frequently noted radial hand abnormalities require the
      majority of surgical procedures. Such a classification based on the thumb and
      first-web deformities will focus the surgeon's attention on those deficiencies
      that are most important for the restoration of function. It is proposed that
      ulnar deficiency be classified by one of the classification schemes that
      describes the anatomy of the forearm and/or elbow supplemented by the hand
      classification type.

PMID- 9195459
TI  - Congenital absence of the scaphoid without other congenital abnormality: a case
      report.
AB  - Congenital absence of the scaphoid without associated thumb or radial hypoplasia
      is a rare condition. This report is the third case presented in the literature of
      this condition. The case presented is of a patient who presented initially with
      wrist pain. Radiographs revealed a congenitally absent scaphoid and examination
      revealed no evidence of thumb hypoplasia. A brief review of the literature on
      congenital absence of the scaphoid is discussed.

PMID- 9195460
TI  - Acrocallosal syndrome: a case report.
AB  - This report describes the case of an 18-month-old Caucasian male infant with
      clinical and radiological findings indicative of the Schinzel acrocallosal
      syndrome. He was born to non-consangiuneous parents. His father had been
      diagnosed with Greig syndrome. The patient underwent surgery for preaxial
      polysyndactyly of both hands and feet. The similarity to the Greig syndrome is
      discussed. It is possible that both the acrocallosal syndrome and the Greig
      syndrome are variant expressions of the same autosomal dominant condition.
      Surgery may improve thumb opposition and shoe wear.

PMID- 9195461
TI  - Limb salvage surgery and adjuvant radiotherapy for soft tissue sarcomas of the
      forearm and hand.
AB  - Twenty-five consecutive patients with soft tissue sarcoma of the forearm and hand
      were assessed for limb-salvage surgery and were entered into a prospective study
      evaluating oncologic details and functional outcome. Seventeen patients had
      received incomplete primary excision elsewhere and presented with local
      recurrence or residual disease. Three had pulmonary metastases at the time of
      presentation. Twenty-three patients were candidates for limb-salvage surgery and
      20 received adjuvant radiotherapy. The mean follow-up period was 37 months. There
      was local recurrence in three patients who had initially received marginal
      excision of the primary sarcoma, and three patients died of systemic disease.
      Limb function was assessed prospectively using both patient-based and clinician
      based functional scoring systems and revealed good to excellent results in all
      but three patients. Eighty-eight percent of those who survived and did not
      require amputation were able to return to occupational and activities of daily
      living with no or minimal functional limitation. This study demonstrates that
      limb-salvage surgery, with adjuvant radiotherapy when necessary, is an effective
      alternative to amputation in the majority of patients with sarcoma of the forearm
      and hand. Radiation toxicity is rarely a problem.

PMID- 9195462
TI  - Autogenous fibular graft and silicone implant arthroplasty following resection of
      giant cell tumor of the metacarpal: a report of two cases.
AB  - Two cases of reconstruction after resection of giant cell tumor of the distal
      metacarpal are reported in which reconstruction was achieved with a
      nonvascularized fibular autograft and silicone metacarpophalangeal joint
      arthroplasty. At 2-year and 1-year follow-up evaluation, respectively, the
      patients were found to be doing well. This method of reconstruction appears
      reliable and presents the possibility for vascularized reconstruction if that is
      thought necessary.

PMID- 9195463
TI  - Synchronous glomus tumors in a distal digit: a case report.
AB  - Glomus tumors occurring synchronously in the subungual region and the pulp of a
      fingertip are extremely uncommon. Awareness of this will lead to early diagnosis
      and treatment.

PMID- 9195464
TI  - Malignant eccrine poroma of the hand: a case report.
AB  - Carcinoma of sweat glands is a very rare neoplasm that is difficult to diagnose
      clinically and histologically. This report presents a case of malignant eccrine
      poroma of the hand which is a distinct histologic subtype of sweat gland
      carcinoma with a high local recurrence rate. A distal radial artery based forearm
      flap was used to provide soft tissue coverage.

PMID- 9195465
TI  - Neurocutaneous island flaps in upper limb coverage: experience with 44 clinical
      cases.
AB  - The vascularity of the cutaneous nerve of the upper limb is closely connected
      with the vascularity of the skin. Both skin and nerves are vascularized by
      perforators of the main arteries. Small longitudinal paraneural vessels, in close
      contact with the cutaneous nerves that they supply, link these perforating
      arteries. Based on these anatomic findings, 44 cutaneous flaps (so-called
      neurocutaneous flaps, supplied by the vessels around and inside the cutaneous
      nerves) were raised. The neurocutaneous flap provided reliable coverage of skin
      defects in the upper limb. The flap dimensions were as large as 4 x 10 cm. The
      proximally based flaps were extremely safe, as were the free flaps and the flaps
      based distally on the dorsal side of the hand. One flap distally based on the
      medial antebrachial cutaneous nerve of the forearm and three used in thumb
      reconstruction underwent necrosis. Neurocutaneous island flaps are easy to
      dissect, they are reliable and versatile, and major vessels like the radial,
      ulnar, and posterior interosseous arteries are preserved. In the majority of
      cases, the donor site may be closed primarily and donor site morbidity is
      minimal.

PMID- 9195466
TI  - Circumferential wrapping of a flap around a scarred peripheral nerve for salvage
      of end-stage traction neuritis.
AB  - Nine patients with chronic severe pain due to end-stage traction neuritis of an
      intact peripheral nerve underwent external neurolysis and epineurectomy or
      epineurectomy and internal neurolysis followed by circumferential wrapping of the
      involved segment of nerve with a pedicle flap or free flap consisting of either
      subcutaneous fat tissue, fascia, or muscle. Seven patients (77%) followed for
      between 1 and 5 years had substantial relief of pain. Two patients (22%) had no
      decrease in their pain at all. Circumferential wrapping may cushion the nerve
      from external pressure on the overlying skin, may isolate the nerve from the
      traction forces of adjacent moving tendons to allow improved gliding of the
      nerve, and may promote revascularization of a scarred nerve. This surgery may be
      indicated for patients with persistent pain following multiple carpal tunnel or
      cubital tunnel surgeries.

PMID- 9195467
TI  - Brachial neuritis presenting as anterior interosseous nerve compression-
      implications for diagnosis and treatment: a case report.
AB  - Brachial plexus neuropathy may present as an isolated peripheral nerve lesion,
      suggesting local compression, when in fact the pathophysiology is a diffuse
      proximal inflammation. The type of management depends on an accurate diagnosis of
      the diffuse lesion with electromyography. A descriptive case of isolated anterior
      interosseus nerve palsy is presented and the literature is reviewed. Analysis of
      the reported cases reveals that anterior interosseus nerve palsies resulting from
      different etiologies are included in the same series and that treatment
      recommendations are highly specialty-oriented. Cases of brachial plexus neuritis
      induced anterior interosseus nerve palsy should be managed conservatively, while
      surgical decompression may be performed for specific instances of direct trauma.

PMID- 9195468
TI  - Antithrombotic potencies of enoxaparin in microvascular surgery: influence of
      dose and administration methods on patency rate of crushed arterial anastomoses.
AB  - This study evaluated the influence of the dose and administration methods of
      enoxaparin, a low-molecular-weight heparin, on the patency rate of crushed rat
      femoral arteries following anastomosis. An impact crush with a 25-kg magnitude
      was applied to a 2-mm segment of 100 rat femoral arteries, followed by
      anastomosis. The arteries were divided into five groups: group 1 received
      systemic enoxaparin alone with a relatively high dose (45 IU) twice a day for 3
      days; groups 2 and 3 received topical irrigation with a lower (15 IU/mL)
      concentration and a higher (45 IU/mL) concentration, respectively; group 4
      received systemic and topical application at a lower (15 IU) dose and
      concentration (15 IU/mL); and group 5 received systemic and topical application
      at a higher (45 IU) dose and concentration (45 IU/mL). The results of this study
      demonstrate the following: (1) topical irrigation with enoxaparin at a
      concentration of 45 IU/mL-three times higher than that recommended for clinical
      use adjusted by body weight (15 IU/mL)-is effective for antithrombotic action;
      (2) a combination of systemic and local application does not offer additional
      benefit in the patency rate when compared to local irrigation alone; (3) systemic
      administration alone does not prevent thrombus formation; and (4) enoxaparin is
      potentially useful to enhance the patency rate in compromised microvessels.

PMID- 9195469
TI  - The lateral epicondyle as a bone graft donor site in procedures about the elbow.

PMID- 9195470
TI  - Lengthening of the finger fillet flap to cover dorsal wrist defects.

PMID- 9195471
TI  - Post-transcriptional regulation of gene expression by androgens: recent
      observations from the epidermal growth factor gene.

PMID- 9195473
TI  - Cloning, sequencing and in vitro functional expression of recombinant donkey
      follicle-stimulating hormone receptor: a new insight into the binding specificity
      of gonadotrophin receptors.
AB  - Among all mammalian FSH receptors (FSH-R; including donkey (dk) FSH-R), only
      horse (hs) FSH-R does not bind hsLH/chorionic gonadotrophin (CG). In order to
      delineate the structural origin of hsFSH-R specificity precisely, we have cloned
      dkFSH-R cDNA from donkey testis mRNA by RT-PCR. Transiently expressed dkFSH-R
      endowed COS-7 cells with both hsLH/CG- and FSH-binding activity, as well as FSH
      induced cAMP production. The deduced dkFSH-R amino acid sequence shares 96%
      identity with the hsFSH-R: notably, in the hormone-binding domain, the
      specificity of hsFSH-R may be ascribed to only four divergent amino acids: Thr
      173, Asp 202, Asn 268 and Pro 322. Interestingly, hsAsn 268 could bear an
      additional N-glycosylation. According to receptor negative specificity, these
      amino acids could be implicated in preventing LH/CG binding to FSH-R.

PMID- 9195472
TI  - Effects of withdrawal of dopamine on translocation of protein kinase C isozymes
      and prolactin secretion in rat lactotroph-enriched pituitary cells. Modulation of
      substance P-mediated responses.
AB  - The present study deals with the effects of withdrawal of dopamine (DA) on the
      translocation of protein kinase C (PKC) isozymes and release of prolactin (Prl)
      in resting- and substance P (SP)-stimulated cultures of enriched rat pituitary
      lactotrophs. Following a brief tonic input (10 min), DA withdrawal induced a
      redistribution of PKC alpha- and beta-immunoreactivity (IR) to the particulate
      fraction with maximal levels, attained after 5 min, remaining translocated for 20
      min. DA withdrawal prolonged the effect of SP-induced translocation of PKC alpha-
      and beta-IR. Similar effects were detected when the catalytic activity of PKC in
      response to DA withdrawal was evaluated. Thus, DA washout redistributed PKC
      catalytic activity and prolonged the effect of SP on catalytical PKC
      translocation to the particulate fraction. Pretreatment of cells with the protein
      kinase A inhibitor, rp-adenosine-3',5'-cyclic monophosphothionate (rp-cAMP),
      reduced the amount of PKC alpha- and beta-IR redistributed after DA withdrawal.
      Furthermore, this treatment also reduced the DA withdrawal effect on SP-mediated
      translocation of PKC alpha- and beta-IR. Methoxyverapamil, a blocker of voltage
      gated Ca2+ channels, completely inhibited the redistribution of PKC isozymes
      after DA withdrawal, but also reduced the potentiating effect of DA withdrawal on
      SP-induced redistribution of PKC isozyme-IR. In perifused enriched lactotrophs,
      DA withdrawal induced a release of Prl that lasted 45-55 min and prolonged the
      effect of SP on Prl secretion. rp-cAMP did not significantly affect Prl release
      due to DA removal, but the prolonging effect of DA withdrawal on SP-induced Prl
      secretion was abolished. Methoxyverapamil completely abolished the rebound
      release of Prl after DA withdrawal, and the potentiating effect of DA removal on
      SP-mediated Prl release was also diminished. Readdition of DA after DA withdrawal
      was able to suppress the translocation of PKC isozyme-IR and catalytic activity
      and to reduce the release of Prl to baseline levels. Moreover, readdition of DA
      reduced the potentiating effects of DA withdrawal on the same parameters after SP
      stimulation of cells. On the basis of these results it is concluded that in
      resting cells following DA withdrawal prolactin is released and specific PKC
      isozymes and concomitant catalytic activity are translocated to the particulate
      fraction in enriched lactotrophs. While cAMP/PKA and influx of Ca2+ seem to work
      in concert in translocating PKC, influx of Ca2+ is the primary mechanism
      responsible for the rebound release of Prl after DA withdrawal. DA withdrawal
      exerts a potentiating effect on SP-induced PKC translocation and Prl release. It
      is suggested that the biochemical events involved in these processes are cAMP/PKA
      and Ca2+ influx.

PMID- 9195474
TI  - Promoter and species specific differential estrogen-mediated gene transcription
      in the uterus and cultured cells using structurally altered agonists.
AB  - Certain types of estrogenic compounds have been shown to have tissue-specific
      actions. In addition, some tissues may exhibit differential gene regulation by
      agonists and antagonists. Our previous studies using structurally modified
      estrogenic molecules had indicated differential effects on specific estrogen
      responses, indicating that the activity of the estrogen receptor protein can be
      altered depending not only upon the structure of the bound ligand but also the
      regulated gene itself. The mechanism of differential induction, however, was not
      determined, and might involve altered binding to the estrogen response element
      (ERE), altered transcription, or post-transcriptional modification of gene
      products. Our previous studies indicated that differential induction by modified
      diethylstilbestrol (DES) agonists could not be accounted for by differences in
      ligand affinity for the estrogen receptor (ER) or differential binding of the ER
      to a consensus vitellogenin A2 (vit A2) ERE. To determine if this differential
      hormonal responsiveness was reflected at the level of transcription, we analyzed
      mouse uterine mRNA of several estrogen-responsive genes, including glucose-6
      phosphate dehydrogenase (G6PD), ornithine decarboxylase (ODC) and lactoferrin, by
      Northern blot following injection with the modified agonists DES, indenestrol A
      (IA), indenestrol B (IB) and Z-pseudo DES (ZPD). All compounds induced the G6PD
      message, although IB and ZPD induced expression only transiently, while DES and
      IA maintained the message for 24 h. No difference in induction was seen for ODC
      message, which was induced equally by all the compounds. In contrast,
      lactoferrin, a highly estrogen-responsive gene, was induced only by DES and IA
      and not by the other agonists IB or ZPD, showing that the lactoferrin gene was
      differentially regulated by these compounds. To determine whether this difference
      was due to altered transcriptional activity, the mouse lactoferrin estrogen
      responsive module (mERM) linked to a chloramphenicol acetyl transferase (CAT)
      reporter gene was tested in transfected cells. Using the mouse estrogen receptor
      in RL95 cells, DES and IA induced expression of CAT, but IB did not, confirming
      the differential response seen in vivo. To show whether this difference in
      transcription occurred because of altered binding to the lactoferrin ERE, which
      is not a perfect consensus ERE a gel shift assay was used to examine DNA binding
      of ER bound to the agonists. All ligands produced equivalent binding to the
      lactoferrin ERE suggesting that differential regulation was not a result of
      altered DNA binding. Taken together, these observations indicate that the
      differential induction of lactoferrin by these compounds occurs via altered
      activation of the transcriptional components unique to lactoferrin and is likely
      to involve altered interaction with co-activators. Surprisingly, unlike the mouse
      ER, the human estrogen receptor activated and induced expression of lactoferrin
      estrogen-responsive module-CAT with all the compounds. Mouse ER is also known to
      vary from the human ER in its activity with the triphenylethylene estrogen
      tamoxifen, which has agonist activity with the mouse ER but mixed
      antagonist/agonist activity with the human ER. The data show that human and mouse
      estrogen receptors are activated differently by this group of stilbestrol
      estrogen ligands when assayed on the lactoferrin response element, which is the
      first description of this type of gene and species specific difference.
      Lactoferrin gene regulation by estrogen receptor can be used as a model to study
      the mechanism of differential gene activation by different estrogen agonists and
      antagonists using a more physiological situation than commonly used with in vitro
      gene reporter systems.

PMID- 9195475
TI  - The role of GH receptor tyrosine phosphorylation in Stat5 activation.
AB  - Stimulation of GH receptors leads to rapid activation of Jak2 kinase and
      subsequent tyrosine phosphorylation of the GH receptor. Three specific tyrosines
      located in the C-terminal domain of the GH receptor have been identified as being
      involved in GH-stimulated transcription of the Spi 2.1 promoter. Mutated GH
      receptors lacking all but one of these three tyrosines are able to mediate a
      transcriptional response when transiently transfected into CHO cells together
      with a Spi 2.1 promoter/luciferase construct. Similarly, these GH receptors were
      found to be able to mediate activation of Stat5 DNA-binding activity, whereas the
      GH receptor mutant lacking all intracellular tyrosines was not. Synthetic
      tyrosine phosphorylated peptides corresponding to the GH receptor sequence around
      the three tyrosines inhibited Stat5 DNA-binding activity while their non
      phosphorylated counterparts were ineffective. Tyrosine phosphorylated GST-GH
      receptor fusion proteins specifically bound to Stat5 in extracts from COS 7 cells
      transfected with Stat5 cDNA. This binding could be inhibited by tyrosine
      phosphorylated peptides derived from the GH receptor. This study thus
      demonstrated that specific GH receptor tyrosine residues, in their phosphorylated
      state, are involved in transcriptional signaling by directly interacting with
      Stat5.

PMID- 9195476
TI  - Transcriptional and post-transcriptional regulation of prolactin during the
      turkey reproductive cycle.
AB  - The present study examined turkey prolactin (PRL) transcription and PRL mRNA
      stability during different reproductive stages. Nuclear run-on transcription
      assays were performed using isolated nuclei from pituitaries of turkeys at
      different reproductive stages. Meanwhile, cytoplasmic PRL mRNA and plasma PRL
      were measured by slot blot and RIA respectively. The PRL transcription, pituitary
      cytoplasmic PRL mRNA abundance and plasma PRL levels increased after
      photostimulation and peaked at the incubating stage (P < 0.05). A decrease in PRL
      transcription, pituitary cytoplasmic PRL mRNA and plasma PRL (P < 0.05) was
      observed during the transition from incubation to photorefractoriness. Nest
      deprivation reduced circulating PRL (P < 0.05), whereas pituitary cytoplasmic PRL
      mRNA and PRL transcription were not significantly altered from those in
      incubating birds (P > 0.05). The half-life of PRL mRNA was determined in
      pituitaries of non-photostimulated, laying, incubating and photorefractory hens.
      Primary pituitary cell cultures were treated with the transcription inhibitor
      actinomycin-D and the decay of the pre-existing PRL mRNA was quantified using
      Northern blot analysis. The PRL mRNA half-life was 1.5- and 1.4-fold greater in
      incubating and laying birds respectively than in non-photostimulated turkeys (P <
      0.05). The half-life of PRL mRNA in photorefractory and incubating hens was
      similar in spite of great differences in pituitary PRL mRNA steady-state levels
      and PRL transcription. Our data suggest that photoinduced changes in pituitary
      PRL mRNA and plasma PRL are due to changes in both PRL transcription and PRL mRNA
      stability. Nest-deprivation inhibits the PRL releasing mechanism(s) independently
      of PRL transcription in turkeys.

PMID- 9195477
TI  - Downregulation of IGF-I mRNA expression during postnatal pancreatic development
      and overexpression after subtotal pancreatectomy and acute pancreatitis in the
      rat pancreas.
AB  - Insulin-like growth factors (IGFs) are important peptides involved in the
      regulation of cell growth and differentiation in many tissues. The ontogeny of
      IGF-I was examined in pancreata from 19-day rat fetuses, newborns and 5-, 11-, 26
      and 70-day-old rats. For the regeneration studies two models were used: (i) 90%
      pancreatectomy was carried out and the rats were killed at 1, 2, 3 and 6 days
      after resection; (ii) acute pancreatitis was induced with caerulein (12
      micrograms/body weight three times a day every 8 h for 2 days) and the rats were
      killed at 1, 2, 5, 7 and 9 days after the first injection. Total RNA was
      extracted by the guanidinium isothiocyanate method and Northern blots were
      performed using total RNA and labeled cRNA probes. Abundance of the different
      mRNA transcripts was estimated by densitometric scanning and normalized to the
      abundance of 18 S rRNA for each time point. Northern blot analysis during
      ontogeny showed four (0.8-1.2, 1.9, 4.7 and 7.5 kb) major transcripts in the rat
      pancreas and liver. Total IGF-I mRNA was 40-fold higher in the adult liver than
      in the adult pancreas. Moreover, in the liver, IGF-I mRNA levels were higher in
      the adult than in the fetus, whereas in the pancreas, the highest levels were
      observed around birth. During the first 3 days after pancreatectomy, a peak of
      maximal expression was observed after the second day. Densitometric analysis of
      each IGF-I mRNA species showed concomitant increases in all transcripts. After 6
      days, all transcripts had returned to near-control values. IGF-I mRNA expression
      2 days after pancreatectomy was 3.5-fold higher than in the newborn. During the
      first 2 days of acute pancreatitis induction, overexpression of IGF-I mRNA was
      observed. However, soon after the second day of caerulein treatment, the 7.5 kb
      transcripts remained elevated whereas those of the others regressed toward
      control values. Our results show that IGF-I mRNA is overexpressed in both models
      of pancreatic regeneration but downregulated in the normal adult pancreas.

PMID- 9195479
TI  - Homodimer formation by the individual subunits of bovine lutropin as determined
      by sedimentation equilibrium.
AB  - Although differing in their amino acid sequences, the folding patterns of the
      alpha and beta subunits of human choriogonadotropin are similar in the crystal
      structure of the HF-treated glycoprotein hormone. Each subunit forms a cystine
      knot motif like that found in several growth factors that form homodimers and
      heterodimers. In order to ascertain if the alpha and beta subunits can self
      associate, e.g. to form homodimers, sedimentation equilibrium at various
      glycoprotein concentrations and temperatures was used to study the subunits of
      bovine lutropin, which are expected to exhibit conformations like those of the
      choriogonadotropin subunits. Each subunit was found to form homodimers with Kd
      values of 0.3 and 0.1 mM for alpha and beta respectively at 37 degrees C. Self
      association was weakly exothermic for alpha and endothermic for beta; entropic
      factors made a major contribution for each. It is unlikely that homodimer
      formation of either subunit would be physiologically important, although
      homodimers may form to some extent intracellularly because of the relatively high
      concentrations during biosynthesis.

PMID- 9195478
TI  - Inappropriate expression of human transforming growth factor (TGF)-alpha in the
      uterus of transgenic mouse causes downregulation of TGF-beta receptors and delays
      the blastocyst-attachment reaction.
AB  - In the mouse, the initiation of the attachment reaction between the blastocyst
      trophectoderm and luminal epithelium of the receptive uterus occurs in the
      evening (2200-2300 h) of day 4 of pregnancy (day 1 = vaginal plug) and is
      followed by proliferation and differentiation of stromal cells into decidual
      cells at the sites of blastocyst attachment. This investigation demonstrates that
      an inappropriate expression of the human transforming growth factor alpha (hTGF
      alpha) transgene in the uterus under the direction of a mouse metallothionein-I
      promoter downregulates uterine expression of TGF-beta receptor subtypes and
      delays the initiation of implantation (attachment reaction) resulting in delayed
      parturition. This delay in the attachment reaction is accompanied by deferred
      uterine expression of amphiregulin. The results suggest that a coordinated 'cross
      talk' between the signaling pathways executed by epidermal growth factor-like
      growth factors and TGF-beta 5 is important for the normal implantation process.

PMID- 9195480
TI  - The interaction of CGRP and adrenomedullin with a receptor expressed in the rat
      pulmonary vascular endothelium.
AB  - An abundant, seven trans-membrane domain receptor related to the calcitonin
      receptor has been studied by a number of groups without identification of its
      ligand. A recent report claimed that the receptor was a type 1 CGRP receptor
      (Aiyar et al J. Biol. Chem. 271 11325-11329 (1996)). We have studied the
      equivalent rat sequence in transfected cells. When expressed in 293 cells the
      receptor interacts with CGRP and adrenomedullin with KD values of 1.2 nM for CGRP
      and 11 nM for adrenomedullin. Both ligands cause an elevation of intracellular
      cAMP with EC50 values of 4 nM and 20 nM respectively and these effects are
      inhibited by the antagonist CGRP8-37. The receptor is expressed at high levels in
      the pulmonary vascular endothelium. Both the pharmacological data and the
      localisation are consistent with the conclusion that the orphan receptor is a
      type J CGRP receptor. However, when expressed in COS-7 cells, no receptor
      activity could be demonstrated suggesting that 293 cells contain a factor
      necessary for functional receptor expression.

PMID- 9195481
TI  - Nutritional regulation of insulin-like growth factor-I mRNA expression in
      barramundi, Lates calcarifer.
AB  - The effect of nutritional status on IGF-I mRNA expression in the liver and brain
      of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed
      a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated
      significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6
      weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was
      10 fold lower than the liver and was not affected by ration size. These results
      suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not
      brain IGF-I mRNA expression is regulated by food availability in juvenile
      barramundi.

PMID- 9195482
TI  - Modeling polysaccharides: present status and challenges.
AB  - The most recent tools that have been developed for modeling the three-dimensional
      features of polysaccharides and carbohydrate polymers are presented. The
      presentation starts with a description of the conformations of the
      monosaccharides, and of the flexible rings such as in the case of five-membered
      rings, and a thorough description of the conformational space that is available
      for a disaccharide unit, either in vacuo or in an aqueous phase. The extension to
      the modeling of the parent polysaccharides is addressed, based on the assumption
      that owing to the size and relative rigidity of the intervening monosaccharides
      units, the rotations at a particular linkage can be, under some conditions,
      considered as independent of nearest neighbor interactions. Appropriate modeling
      techniques are described that can provide insights into the dimensions of the
      chain in a solution which is best described as a random coil accompanied by the
      occurrence of local "helical" regions. With the help of such descriptors such as
      helical parameters, the ordered state of polysaccharide strands can be readily
      characterized. The generation of double or triple helices can be then attempted
      in order to explore the occurrence of such multi-stranded arrangements that may
      be energetically stable. The final step in the determination of the structure of
      polysaccharides in the ordered state, is the investigation of the interactions of
      different helices. This may lead to either the best arrangement(s) between two
      polymeric chains, or to the prediction of the dimensions, and the symmetry of a
      three-dimensional lattice. Some of the tools which have been developed should
      allow automatic scarches for meaningful correlations between structures and
      functions, through exploratory data analysis. Structure-function or structure
      property correlation could be then used to model changes arising from structural
      alterations. This would open the field of polysaccharide engineering.

PMID- 9195484
TI  - Why spin = 1, 2 species have no electron paramagnetic resonance signal under
      normal conditions: possible detection by electron paramagnetic resonance at
      frequency close to D value?
AB  - A universal EPR simulation program has been created by the author, which is based
      on the following spin Hamiltonian equation: [equation: see text] where D and E
      are the axial and rhombic zero-field splitting parameters, respectively. The
      program can be used for simulation of EPR spectra with half-integer electronic
      spin (S = n/2, n = 3, 5, 7, 9) systems. In this article, the integer spin (S =
      n/2, n = 2, 4) systems are also considered. The EPR simulation results show that
      when D > frequency, no EPR signal can be seen from EPR simulation; when D
      approximately frequency, whichever X/Q/W-band is used, the EPR signal can be seen
      on the basis of the simulated EPR results presented.

PMID- 9195483
TI  - Knowledge-based modeling of a legume lectin and docking of the carbohydrate
      ligand: the Ulex europaeus lectin I and its interaction with fucose.
AB  - Ulex europaeus isolectin I is specific for fucose-containing oligosaccharide such
      as H type 2 trisaccharide alpha-L-Fuc (1-->2) beta-D-Gal (1-->4) beta-D-GlcNAc.
      Several legume lectins have been crystallized and modeled, but no structural data
      are available concerning such fucose-binding lectin. The three-dimensional
      structure of Ulex europaeus isolectin I has been constructed using seven legume
      lectins for which high-resolution crystal structures were available. Some
      conserved water molecules, as well as the structural cations, were taken into
      account for building the model. In the predicted binding site, the most probable
      locations of the secondary hydroxyl groups were determined using the GRID method.
      Several possible orientations could be determined for a fucose residue. All of
      the four possible conformations compatible with energy calculations display
      several hydrogen bonds with Asp-87 and Ser-132 and a stacking interaction with
      Tyr-220 and Phe-136. In two orientations, the O-3 and O-4 hydroxyl groups of
      fucose are the most buried ones, whereas two other, the O-2 and O-3 hydroxyl
      groups are at the bottom of the site. Possible docking modes are also studied by
      analysis of the hydrophobic and hydrophilic surfaces for both the ligand and the
      protein. The SCORE method allows for a quantitative evaluation of the
      complementarity of these surfaces, on the basis of molecular lipophilicity
      calculations. The predictions presented here are compared with known biochemical
      data.

PMID- 9195485
TI  - Affecting the activity of soybean lipoxygenase-1.
AB  - The iron content in soybean lipoxygenase-1 is important for enzyme activity. If
      the iron is removed by a chelating agent, the activity of the enzyme will
      decrease. The active center includes the iron ligands and the surrounding
      environment, and any conformational change in the active center may affect the
      activity of the enzyme. It is shown that the activity of soybean lipoxygenase-1
      is enhanced by chloride anion, phosphate, formate, borate, etc., especially at a
      lower concentration of substrate. It is also shown that one of four thiols in
      soybean lipoxygenase-1 is accessible to DTNB at 0.1% SDS without losing great
      activity, and that all four thiols are accessible to DTNB at 1% SDS and lose all
      activity. Two or three of the four thiols are accessible to mercuric cyanide
      without losing great activity. These results support the hypothesis that only
      one, or possibly two cysteines are responsible for the loss of activity. Two
      substrate and two-product binding site models are proposed here and discussed in
      view of high-resolution X-ray crystal structure.

PMID- 9195486
TI  - Prediction of high-frequency electron paramagnetic resonance spectra of spin S =
      3/2, 5/2 systems.
AB  - By the use of the universal EPR simulation program created by the author, spin S
      = 3/2 and S = 5/2 systems are studied and their simulated EPR spectra at high
      frequencies (Q-band for 35 GHz and W-band for 95 GHz) are presented here. The
      mononuclear Fe3+ in rubredoxin, isolated from Pseudomonas oleovorans (which is an
      S = 5/2 system with D = 1.76 cm-1 and E/D = 0.28), is extensively studied by EPR
      spectrum simulation at the Q-band, W-band, and "Z"-band. The molybdenum- and iron
      containing protein (MoFe protein), which has g values at g = 4.32, 3.65, and 2.01
      (S = 3/2, D = 6.0 cm-1, and E/D = 0.055) at the X-band, is also studied by EPR
      spectrum simulation at high frequencies.

PMID- 9195487
TI  - Analytically defined surfaces to analyze molecular interaction properties.
AB  - Molecular surfaces are widely used for characterizing molecules and displaying
      and quantifying their interaction properties. Here we consider molecular surfaces
      defined as isocontours of a function (a sum of exponential functions centered on
      each atom) that approximately represents electron density. The smoothness is
      advantageous for surface mapping of molecular properties (e.g., electrostatic
      potential). By varying parameters, these surfaces can be constructed to represent
      the van der Waals or solvent-accessible surface of a molecular with any accuracy.
      We describe numerical algorithms to operate on the analytically defined surfaces.
      Two applications are considered: (1) We define and locate extremal points of
      molecular properties on the surfaces. The extremal points provide a compact
      representation of a property on a surface, obviating the necessity to compute
      values of the property on an array of surface points as is usually done; (2) a
      molecular surface patch or interface is projected onto a flat surface (by
      introducing curvilinear coordinates) with approximate conservation of area for
      analysis purposes. Applications to studies of protein-protein interactions are
      described.

PMID- 9195488
TI  - HOLE: a program for the analysis of the pore dimensions of ion channel structural
      models.
AB  - A method (HOLE) that allows the analysis of the dimensions of the pore running
      through a structural model of an ion channel is presented. The algorithm uses a
      Monte Carlo simulated annealing procedure to find the best route for a sphere
      with variable radius to squeeze through the channel. Results can be displayed in
      a graphical fashion or visualized with most common molecular graphical packages.
      Advances include a method to analyze the anisotropy within a pore. The method can
      also be used to predict the conductance of channels using a simple empirically
      corrected ohmic model. As an example the program is applied to the cholera toxin
      B-subunit pentamer. The compatibility of the crystal structure and conductance
      data is established.

PMID- 9195489
TI  - Preferential radiosensitization of 9L glioma cells transduced with HSV-tk gene by
      acyclovir.
AB  - The antiviral drug acyclovir, an analogue of purine, was found to selectively
      enhance the radiosensitivity of rodent tumor cells which were transduced with the
      herpes simplex virus thymidine kinase gene (HSV-tk). 9L rat glioma cells
      transduced with HSV-tk and treated with acyclovir (20 micrograms/ml) for 24 hr
      before or after irradiation were highly sensitive to radiation, as compared with
      non-transduced glioma cells. When 9L cells transduced with HSV-tk gene were
      exposed to acyclovir and radiation, the sensitizer enhancement ratio (SER) was
      1.6. In vivo, a significant increase in the median survival time of rats with 9L
      tk tumors was observed when acyclovir was administered before and after single
      dose irradiation, relative to the survival time of similar rats receiving
      radiation alone. The results show that an antiviral agent can selectively enhance
      cell killing by radiation in cells transduced with the HSV-tk, and suggest that
      the addition of HSV-tk gene therapy to standard radiation therapy will improve
      the effectiveness of treatment for brain tumors.

PMID- 9195490
TI  - Effect of irradiation on transforming growth factor-beta secretion by malignant
      glioma cells.
AB  - Glioblastoma cells secrete transforming growth factor-beta (TGF-beta), which has
      a variety of immunosuppressive properties. We investigated the effect of
      irradiation TGF-beta secretion by malignant glioma cells. Three malignant glioma
      cell lines (T98G, A172, KG-1-C) were cultured and irradiated using 10 and 50 Gy
      Linac radiation. After further culture for 36 hours in serum-free culture medium,
      the supernatants were collected. The TGF-beta activity in the culture
      supernatants was determined using a specific bioassay. The levels of the active
      form and total TGF-beta in the supernatants from irradiated malignant glioma
      cells decreased compared to those from un-irradiated cells. However, since
      irradiation inhibited the growth of tumor cells, the amount of TGF-beta secretion
      per cell in irradiated cells tended to increase after irradiation. These results
      suggest that malignant glioma cells can still secrete TGF-beta and activate
      latent TGF-beta even after large dose irradiation, despite the inhibition of
      tumor growth.

PMID- 9195491
TI  - A prospective study of short course radiotherapy in elderly patients with
      malignant glioma.
AB  - Elderly patients with malignant glioma have a poor prognosis and the benefit of
      standard radical radiotherapy is equivocal. Twenty-two percent of the adult
      referral base with malignant glioma at our centre is of age 70 years or greater.
      A phase II study was undertaken to determine if a shorter course of therapy
      yields a comparable median survival to radical radiotherapy and thus constitutes
      an appropriate investigational palliative regimen. 25 patients were accrued
      between 1988-1995, all of whom had histologically proven malignant glioma, 23
      glioblastoma multiforme and 2 anaplastic astrocytoma. The median age was 73
      (range 70-78) and median Karnofsky Performance Status (KPS) was 70.40% had a
      stereotactic biopsy only for diagnosis. Radiotherapy was delivered to limited
      fields to a dose of 37.5 Gy in 15 daily fractions over 3 weeks. An intention-to
      treat analysis was undertaken with survival determined from date of initial
      consultation. The median survival of the whole group was 8.0 months (95% CI 4.8
      9.6). Patients with good performance status (KPS > 70) had a median survival of
      10.4 months (95% CI 9.6-14.7). 37.5 Gy in 15 daily fractions appears to yield
      comparable median survival to that of other series of radical radiotherapy. A
      phase III study of this regimen is recommended in investigating optimal
      palliation of elderly malignant glioma patients.

PMID- 9195492
TI  - Conservative surgery and radiotherapy in the treatment of spinal cord
      astrocytoma.
AB  - Spinal cord astrocytomas are rare neoplasms, and optimal treatment guidelines are
      undefined, 23 patients with spinal cord astrocytomas were treated between 1984
      and 1993 with conservative surgery and postoperative radiotherapy. The mean age
      was 31 years. Twelve patients were male and eleven female. All patients presented
      with neurologic deficit. Cervical cord was involved in five patients,
      cervicothoracic in four, thoracic in eight and thoracolumbar in six. Five
      patients had intramedullary cysts. Fifteen patients had low grade tumors and six
      high grade. Surgery was near total excision in three patients, partial excision
      in ten and biopsy in ten patients. All patients received postoperative
      radiotherapy to a median dose of 45 Gy in 25 fractions over 5 weeks. The median
      followup was 51 months (range 7-143 months). At 6 months post radiotherapy,
      twelve patients had improvement of neurologic status, nine had stable status, and
      two deteriorated. The actuarial overall survival was 55% at 5 years and 39% at 10
      years. The actuarial progression free survival probability was 75% at 5 years and
      55% at 10 years. Five patients had local failure and two failed at distant sites.
      Twelve patients died, six due to progressive disease, five due to complications
      of paraplegia and one patient of unrelated causes. Tumor grade was a significant
      prognostic factor for overall survival. 5 year overall survival was 79% for low
      grade tumors. No patient with high grade tumor survived more than 2 years and the
      median survival was 10 months. Low grade, female sex and presence of
      intramedullary cysts were associated with significantly improved progression free
      survival. Conservative surgery followed by radiotherapy appears to have a role in
      achieving tumor control and neurologic recovery in patients with low grade
      astrocytomas of the spinal cord. Treatment results of high grade tumors remain
      poor and new therapeutic strategies need to be studied.

PMID- 9195493
TI  - Permanent low-activity iodine-125 implants for cerebral metastases.
AB  - Beginning in 1987, selected patients with metastatic brain tumors were treated
      with permanent implants of low-activity radioactive iodine-125(125I) seeds. These
      patients underwent craniotomy, gross total resection of the metastatic lesion,
      and placement of the seeds. In general, criteria for treatment included the
      presence of a recurrent tumor with a volume too large to permit radiosurgery, and
      a Karnofsky Performance Score of 70 or higher. Thirteen patients underwent 14
      implant procedures; all received external whole-brain radiotherapy. Implant dose
      ranged from 43 Gy to 132 Gy, with a mean of 83 Gy. Survival after implantation
      ranged from 2 weeks to almost 9 years, with a median of 9 months. Clinical and
      radiographic local control was obtained in 9 patients. Two patients died of
      acute, postoperative complications within a month of implantation, so no
      information regarding tumor control is available for them. Late complications
      included a bone flap infection in one patient and a CSF leak in another; both
      were treated without further sequelae. These results demonstrate that permanent
      125I implants can results in good survival and quality of life, and occasionally
      can yield long-term survival. Potentially, it is a cost-effective treatment in
      that a separate procedure for stereotactic implantation or radiosurgery is not
      needed, as is the case with the use of temporary high-activity seeds. The
      permanent implantation itself adds less than 10 minutes to the craniotomy, and
      the risk of symptomatic radiation necrosis is low. We recommend consideration of
      this procedure in patients harboring large, recurrent metastatic tumors that
      require further surgery.

PMID- 9195496
TI  - Post-operative radiotherapy for recurrent dermoid cysts of the spine: a report of
      3 cases.
AB  - We report three cases of recurrent, intraspinal dermoid cysts managed with post
      operative radical radiotherapy. In all cases, the period between last surgery and
      cystic re-accumulation has been lengthened by the use of involved-field
      radiotherapy. This combined-modality approach could be beneficial in decreasing
      the probability of recurrence associated with incompletely-resected tumours, or
      in patients whose co-morbidities put them at increased operative risk for serial
      neurosurgical procedures.

PMID- 9195497
TI  - Traditions in public health dentistry: a new feature.

PMID- 9195494
TI  - Oligoastrocytomas: a clinicopathological study of 52 cases.
AB  - Oligoastrocytomas form a poorly defined subgroup of glial tumors, and few
      clinical series have been reported. We performed a retrospective study to
      elucidate the histopathological features of these tumors and to relate the
      clinical signs and symptoms and proliferative potential to survival.
      Oligoastrocytomas were defined as glial tumors with at least 10% neoplastic
      astrocytes and 10% neoplastic oligodendrocytes; tumors were graded with the St.
      Anne-Mayo criteria for astrocytomas and oligodendrogliomas. Proliferative
      potential was estimated with antibodies against proliferating cell nuclear
      antigen (PCNA). Median survival of 52 patients (median age, 42 years) was 75
      weeks (range 2-703 weeks). Actuarial 1-, 2-, 3-, and 5-year survival rates were
      67%, 43%, 40%, and 29%, respectively. For 15 patients with grade 3 and 33 with
      grade 4 lesions (St. Anne-Mayo astrocytoma classification), median survival was
      217 and 55 weeks, respectively. For 19 patients with grade 2 and 33 with grade 3
      lesions (St. Anne-Mayo oligodendroglioma classification), median survival was 305
      and 55 weeks, respectively. Interobserver agreement between three experienced
      neuropathologists on identification of astrocytes, oligodendrocytes, and
      unclassifiable cells was low, indicating considerable subjectivity in the
      histopathological diagnosis. Median PCNA labeling indices correlated with tumor
      grade, but individual values varied so widely within grades that they had no
      predictive value for survival. In a multivariate analysis, symptoms of increased
      intracranial pressure and microvascular proliferation were independently
      associated with poor prognosis. The biological behavior of subgroups appeared to
      be distinctly less aggressive than that of 'pure' astrocytomas of similar grade.
      Better histopathological definition of oligoastrocytomas and improved assessment
      of percentages of constituent cell types may allow more accurate prognosis.

PMID- 9195495
TI  - Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT
      plus BCNU in high grade astrocytoma.
AB  - PURPOSE: We performed a randomized trial to compare survival distributions and
      toxicity of radiation therapy (RT) and DBD with RT and BCNU in patients with high
      grade astrocytoma. METHODS: A total of 238 patients with supratentorial grade 3
      and grade 4 astrocytoma were studied. Patients were stratified by age, extent of
      surgery, tumor grade, and performance score and randomly assigned to receive RT
      55-60 Gy and either DBD, 200 mg/m2 orally on Days 1-10 every five weeks or BCNU,
      200 mg/m2 intravenously every seven weeks. Median age was 60 years; 62% were 55
      years or older. Eighty-three percent had subtotal resection, 58% had grade 4
      tumors, and 83% had performance scores of 0-2. RESULTS: Survival distributions
      for all patients in the two arms were similar, with median survival of 41 weeks
      in each arm. Time to progression distributions were virtually identical, with
      medians of 22 weeks. BCNU produced significantly greater hematologic toxicity;
      median leukocyte and platelet nadirs on the first cycle were 3.6 vs. 4.7 (P =
      0.0001) and 117 vs. 162 (P < 0.0001), and overall platelet nadirs were 80.5 vs.
      114 (P = 0.0019). Non-hematologic toxicities were also significantly greater with
      BCNU, including nausea (57% vs. 31%; P < 0.0001) and vomiting (45% vs. 17%; P <
      0.0001). CONCLUSION: This trial found no evidence of differences in treatment
      efficacy when either DBD or BCNU is combined with radiation therapy for patients
      with high-grade astrocytoma.

PMID- 9195499
TI  - Characteristics of patients seeking care from independent dental hygienist
      practices.
AB  - OBJECTIVES: This study determined demographic characteristics, satisfaction with
      care, and likelihood of follow-up dentist visits for patients seen in office
      based, independent, dental hygienist practices. METHODS: New patients were
      surveyed after their initial visits to independent hygienist practices to assess
      their demographic characteristics and satisfaction with care at both the
      beginning of practice operations and 18 months after the start of these
      practices. Follow-up surveys were sent to patients 12 and 24 months after their
      initial visits to the independently practicing dental hygienists to determine if
      patients had visited a dentist. RESULTS: Most respondents were white, female, had
      attended some college, and reported high family incomes. Ninety-eight percent of
      respondents were satisfied with their dental hygiene care. Follow-up
      questionnaires revealed that over 80 percent of respondents visited the dentist
      within 12 months of receiving dental hygiene care in independent settings. This
      level of follow-up care with dentists was found both for respondents who reported
      having a regular dentist at their initial visits with the hygienists and for
      those who reported not having a regular dentist. CONCLUSIONS: Independent
      practice by dental hygienists provided access to dental hygiene care and
      encouraged visits to the dentist.

PMID- 9195498
TI  - Aspects of quality of dental hygiene care in supervised and unsupervised
      practices.
AB  - OBJECTIVE: The purpose of this study was to assess aspects of the quality of care
      provided by dental hygienists in a California demonstration project in which
      hygienists treated patients independent of dentists' supervision. METHODS: The
      structure and process of care were evaluated in nine independent practices using
      site visits and reviews of 25 records at each practice. The findings were
      compared to evaluations of six general dentist practices reviewed for a
      government agency and insurance company during the same time period. Patient
      satisfaction was assessed by a questionnaire. RESULTS: The structural aspects of
      the unsupervised hygienist practices were generally acceptable and surpassed the
      dentist practices in most areas, including infection control. For process, the
      hygienist practices had high percentages of acceptable care and were
      significantly better than the dentist practices in several areas, including
      follow-up to medical findings, updating the medical history at recall, and
      documenting the evaluation of the periodontal status and soft tissues. Ninety
      eight percent of patients expressed satisfaction with their care in hygienist
      practices. CONCLUSION: Under the circumstances of the demonstration project and
      the methods used to assess the quality of care, the study showed that independent
      dental hygienist practice did not increase the risk to the health and safety of
      the public.

PMID- 9195500
TI  - Do root lesions tend to develop in the same people who develop coronal lesions?
AB  - OBJECTIVES: The three purposes of this study are to: (1) describe the
      relationship between the prevalence of coronal caries and root caries; (2)
      describe the relationship between the three-year incidence of coronal caries and
      root caries; and (3) if the two conditions are associated, develop a multiple
      regression model that identifies characteristics distinguishing people who had
      increments of both root caries and coronal caries from people who had increments
      of either coronal caries or root caries, or who had no new caries. METHODS:
      Dental examinations and interviews were conducted in the homes of a randomly
      selected, stratified sample of people over the age of 65 years in five North
      Carolina counties. The relationships between coronal and root D and DF were
      analyzed through contingency table analyses, and ordinal logistic regression was
      used to identify characteristics that differentiated people who had both coronal
      and root D over the three years from people who had either coronal or root D and
      people who had no new disease. RESULTS: Evidence of root and coronal caries in
      whites was much more likely to be in the form of fillings, while for blacks, it
      was more likely to be in the form of untreated decay. Prevalence rates of coronal
      and root D and DF were significantly associated for both blacks and whites.
      Incidence rates based on DF indicated that root and coronal caries were not
      associated in whites, but were associated in blacks. People more likely to
      experience both types of caries had more gingival recession at baseline, greater
      average attachment loss over the three years, and lactobacilli at baseline. In
      addition, the presence of Porphymonas gingivalis at three years was important for
      whites. CONCLUSIONS: It appears that coronal and root caries do tend to appear
      together in the same individuals, but fillings attenuate that relationship. The
      impact of dental treatment on the epidemiology of dental caries appears to be
      considerable and calls into question whether the F component of the caries index
      is related to disease as defined by epidemiologic criteria.

PMID- 9195501
TI  - Genesis of residency programs in dental public health: reflections of the first
      dental public health resident?

PMID- 9195502
TI  - The John W. Knutson Distinguished Service Award in dental public health-1996
      Recipient Dennis Leverett.

PMID- 9195503
TI  - Back to the future: the pyramids of rheumatoid arthritis.
AB  - The management treatment pyramid, treatment target and treatment pyramids provide
      a framework for RA management and treatment. This model brings back the
      traditional pyramid, which was widely accepted, and adapts it to our newer
      understanding of RA treatment. It provides a focus for care, as well as the
      flexibility to apply selective treatments to different temperaments of disease.
      We hope that these models will fill the void left by the abandonment of the
      traditional pyramid. We certainly need a model to refocus the patient and
      physician to the importance of RA and bring "order out of chaos". With our
      current knowledge, resources, and drugs, we could be making a far greater impact
      on this serious, expensive, and crippling disease. We must re-excite and re
      educate the public, the patient, and the profession to the remarkable progress we
      have made with incurable but very treatable arthritis.

PMID- 9195504
TI  - The therapeutic pyramid: a work in progress.

PMID- 9195505
TI  - Subcutaneous administration of CAMPATH-1H: clinical and biological outcomes.
AB  - OBJECTIVE: A 24 week study of subcutaneous (sq) dosing with titration of CAMPATH
      1H (C1H) dose against the circulating CD4+ T cell count in patients with
      rheumatoid arthritis (RA) was undertaken to examine the safety, biologic
      activity, and clinical efficacy of this approach. METHODS: All patients met
      American Rheumatism Association (ARA) criteria for active RA. Patients received
      either 0.5 or 1.0 mg of C1H subcutaneously twice per week; dosing could be
      doubled after the first 8 weeks of treatment and subsequently following 4 week
      dose intervals for lack of clinical efficacy, but was discontinued any time the
      CD4+ T cell count fell below 400/mm3. Patients were evaluated weekly for 2 weeks
      and then biweekly for clinical and laboratory variables of safety, biological
      activity, and disease activity. RESULTS: Ten patients were treated, 6 in the 0.5
      mg cohort and 4 in the 1.0 mg cohort. Four of ten patients had a 20% modified
      Paulus response (2 in each cohort) while taking drug; there were minimal side
      effects, primarily limited to local reaction at the injection site. All patients
      had a > 50% drop in circulating CD4+ T cells within the first 2 weeks of therapy,
      with no further significant reduction; only 1/6 patients in the 0.5 mg cohort had
      dose limiting CD4+ T cell depression vs 2/4 in the 1.0 mg cohort. All patients
      developed antibodies to C1H. Appearance of anti-C1H was temporarily associated
      with a halt in further reduction of CD4+ T cell count despite continued C1H
      administration. CONCLUSION: Subcutaneous administration of C1H in low doses (0.5
      mg biweekly) was well tolerated and did not result in dose limiting CD4+ T cell
      depletion in 5 of 6 patients. Clinical efficacy was observed in some patients but
      could not be maintained, possibly due to the production of anti-C1H antibodies.

PMID- 9195506
TI  - Routine measurement of IgM, IgG, and IgA rheumatoid factors: high sensitivity,
      specificity, and predictive value for rheumatoid arthritis.
AB  - OBJECTIVE: To determine the isotype specificity and clinical utility of routine
      testing by ELISA of IgM, IgG, and IgA rheumatoid factors (RF). METHODS: The test
      was performed on 619 individual specimens: blood bank donors (n = 130);
      rheumatoid arthritis (RA, n = 139); connective tissue diseases (CTD, n = 71);
      miscellaneous rheumatic disorders (MRD, n = 91); and 188 consecutive clinical
      laboratory specimens that tested positive by latex agglutination. Rabbit IgG was
      used as the antigen attached to the solid phase, and rabbit IgG antibody-enzyme
      conjugates against IgM (Fc5mu), IgG[F(ab')2], and IgA (alpha chain) were used,
      respectively, to detect IgM, IgG, and IgA RF. The serum was digested with pepsin
      to facilitate the measurement of IgG RF. RESULTS: All 3 isotypes were
      specifically identified; IgM RF was destroyed by pepsin and IgG RF was
      specifically measured, without interference from IgA RF. Using data obtained from
      98 RA specimens and 162 disease controls, the 3 main clinical variables-
      sensitivity, specificity, and predictive value--were stratified according to 3
      combinations of RF isotypes: IgM only (91, 76, and 62%); IgM+IgA (79, 89, and
      80%), and IgM+IgG+IgA (53, 99, and 96%). For patients with the 3 isotypes plus >
      150 U of IgM and/or IgA the clinical variables were 70, 97, and 93%. In patients
      with RA the IgG RF was found only in association with IgM RF, i.e., there was no
      "hidden" RF, and IgA RF was always accompanied by IgM RF. There was a continuous
      decline in all 3 RF isotypes during treatment with gold salts. The sensitivity of
      ELISA for IgM RF exceeded that of nephelometry or latex agglutination.
      CONCLUSION: Routine measurement of IgM, IgG, and IgA RF by ELISA with rabbit IgG
      as the antigen and pepsin digestion for the detection of IgG RF provides useful
      information in the differential diagnosis of patients with arthritis.

PMID- 9195507
TI  - Evidence for reduced Th1 function in normal pregnancy: a hypothesis for the
      remission of rheumatoid arthritis.
AB  - OBJECTIVE: The mechanisms underlying the pregnancy induced remission of
      rheumatoid arthritis (RA) remain unclear. We assessed the hypothesis that it
      reflects systemic physiologic changes in immune response during gestation.
      METHODS: We used in vitro whole blood culture systems stimulated with either
      lipopolysaccharide or phytohemagglutinin to assess cytokine secretion of cells
      from healthy pregnant and control donors. RESULTS: Interleukin 2 (IL-2)
      production was decreased during pregnancy, more so in the 3rd trimester, and
      soluble tumor necrosis factor (TNF) receptor p55 and p75 was increased, again
      most significantly in the 3rd trimester. TNF-alpha and IL-1 beta were unchanged.
      CONCLUSION: These findings are consistent with the hypothesized downregulation of
      Th1 responses during pregnancy. Further studies to assess the relationship with
      fetal/maternal HLA class II disparity, and eventually the presence or absence of
      remission in actual patients with RA, are required.

PMID- 9195508
TI  - Direct and indirect medical costs incurred by Canadian patients with rheumatoid
      arthritis: a 12 year study.
AB  - OBJECTIVE: To perform the first prospective longitudinal study of direct (health
      services utilized) and indirect costs (diminished productivity represented by
      income loss) incurred by patients with rheumatoid arthritis (RA) in Saskatoon and
      Montreal, followed for up to 12 and 4 years, respectively. METHODS: 1063 patients
      reported on health status, health services utilization, and diminished
      productivity every 6 months. RESULTS: Annual direct costs were $3788 (1994
      Canadian dollars) in the late 1980s and $4656 in the early 1990s. Given that the
      average age exceeded 60 years, few participated in labor force activities or
      considered themselves disabled from the labor force and their indirect costs were
      substantially less, $2165 in the late 1980s and $1597 in the early 1990s.
      Institutional stays and medications made up at least 80% of total direct costs.
      Lengths of stay in acute care facilities remained constant, but the rate of
      hospitalization increased in the early 1990s, increasing average hospital costs
      per patient from $1563 in the late 1980s to $2023 in the early 1990s. For
      nonacute care facilities, rate of admission as well as length of stay increased
      over time, increasing costs per patient in Saskatoon 5-fold, from $291 to $1605.
      Those with greater functional disability incurred substantially higher direct and
      those under 65 years incurred higher indirect costs. CONCLUSION: Direct costs are
      higher than indirect costs. The major component is due to institutional stays
      that, in contrast to other direct cost components, is increased in the older and
      more disabled. Measures to reduce longterm disability by earlier, more aggressive
      intervention have the potential to produce considerable cost savings. However, it
      is unknown which strategies will have the greatest effect on outcome and
      accordingly, how resources can be optimally allocated.

PMID- 9195509
TI  - Mortality studies in systemic lupus erythematosus. Results from a single center.
      III. Improved survival over 24 years.
AB  - OBJECTIVE: Prognosis studies have indicated that survival of patients with
      systemic lupus erythematosus (SLE) has improved significantly. We investigate
      whether the apparent improvement in the survival of patients with SLE is
      associated with a reduction in the risk of death compared with the general
      population, or with changes over time in the distribution of various prognostic
      factors. METHODS: The University of Toronto cohort of 720 patients with SLE
      followed between 1970 and 1994 was divided into 3 groups based on year of entry
      into study: Group A 1970-77, Group B 1978-85, Group C 1986-1994. Standardized
      mortality ratios (SMR) were calculated for each cohort. Prognostic factors for
      death occurring in the first 8 yr period after entry into the study were examined
      in each of the 3 cohorts. Analysis involved chi-squared tests for categorical
      values and unpaired t tests for continuous variables. RESULTS: Group A comprised
      183 patients, Group B 332 patients, and Group C 205 patients. An examination of
      the first 8 years of evaluation for each group revealed that the SMR decrease
      over time ranged from 10.1-fold greater than the general population in Group A,
      to 4.8-fold in Group B, to 3.3-fold in Group C. Prognostic factors for death
      varied over time, with vasculitis decreasing and hyperlipidemia increasing.
      CONCLUSION: Survival in SLE has improved over 24 yrs in the University of Toronto
      cohort more than the health of the general population has improved. This improved
      survival was not related to changing demographics, severity of lupus at
      presentation, major change in disease patterns, or new modalities of treatment.

PMID- 9195510
TI  - Increased nitric oxide in exhaled air of patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: In experimental animals, elevated nitric oxide (NO) production has
      been implicated in the pathogenesis of a lupus-like syndrome. Abnormalities of
      lung function tests are reported in a high proportion of patients with systemic
      lupus erythematosus (SLE). We investigated whether NO output in exhaled air might
      be increased in patients with SLE and whether it is related to disease activity
      and to respiratory function abnormalities. METHODS: Lung volume, maximal
      expiratory flow at 50 and 25% of vital capacity (MEF50 and MEF25), diffusion
      coefficient for carbon monoxide (KCO), and NO in the exhaled air were measured in
      27 outpatients with SLE (23 women, age 39.2 +/- 16.3). NO in exhaled air was also
      measured in 30 healthy control subjects. Disease activity was assessed by the
      European Consensus Lupus Activity Measurement (ECLAM) scoring system. RESULTS:
      Mean values of peak concentrations of NO exhaled air were 64.8 +/- 27.9 parts per
      billion (ppb) in patients and 31.6 +/- 7.7 ppb in controls, p < 0.001. Peak NO
      concentration was directly related to ECLAM activity score (p < 0.05) and
      inversely related to MEF25 (p < 0.05). CONCLUSION: NO in exhaled air is
      significantly increased and correlated with disease activity in patients with
      SLE. Whether increased NO output depends on respiratory tract inflammation, as
      the relationship with MEF25 may suggest, or on circulating cytokines produced
      elsewhere remains to be investigated.

PMID- 9195511
TI  - Longterm ultraviolet-A1 irradiation therapy in systemic lupus erythematosus.
AB  - OBJECTIVE: In a recent series of short term studies ultraviolet-A1 (UV-A1; 340
      400 nm) dermal irradiation proved effective in reducing signs and symptoms of
      disease activity in patients with systemic lupus erythematosus (SLE). To
      determine if the effectiveness persisted with longterm therapy, we followed the
      progress of 6 of these patients for an average of 3.4 (range 2.4-4.5) yrs. The 6
      had had significant decreases in signs and symptoms of disease activity during
      the first 12 weeks of the earlier studies while receiving 3 to 5 low dose UV-A1
      irradiations weekly and were asked to continue into longterm therapy. METHODS:
      Longterm therapy consisted of 1 or 2 irradiations of 6-15 J/m2 (15-30 min, or
      about 1/8-1/4 minimal erythema dose) per week. We assessed their progress every 3
      mo with the systemic lupus activity measures. RESULTS: Despite the smaller number
      of weekly treatments, the gains achieved during the initial 12 weeks of the early
      studies not only persisted but increased slightly. Tanning was moderate to
      absent, the therapy was well tolerated, and there was no apparent toxicity.
      CONCLUSION: UV-A1 radiation induced remissions in SLE persist with longterm
      therapy; 1 or 2 weekly exposures suffice; there appears to be no significant
      toxicity.

PMID- 9195512
TI  - Cytokine manipulation by methotrexate treatment in murine experimental systemic
      lupus erythematosus.
AB  - OBJECTIVE: We reported beneficial effects of methotrexate (MTX) treatment on
      clinical variables in the murine model of experimental systemic lupus
      erythematosus (SLE). We now follow the kinetics of several cytokines that are
      involved in experimental SLE, to find out whether MTX treatment has an effect on
      cytokine production. METHODS: SLE was induced in naive BALB/c female mice by
      injection of the human monoclonal anti-DNA antibody bearing the common idiotype,
      16/6 Id. Six weeks after booster injection, when high levels of autoantibodies
      were observed, MTX treatment was started (2 mg/kg once a week) for 7 months.
      Cytokine production by macrophages or splenocytes from these mice was determined
      monthly by either ELISA or bioassays. RESULTS: A significant increase in the
      production of tumor necrosis factor-alpha was determined as early as 2 weeks
      after injection. Interleukin 1 (IL-1) production increased gradually, starting
      one month after disease induction. These proinflammatory cytokines reached very
      high levels that were maintained through disease course. MTX treatment reduced
      production of these cytokines to normal levels throughout the experimental
      period. Increased levels of IL-2 and interferon-gamma (IFN-gamma), the Th1 type
      cytokines, were detected 2-4 months after disease induction. The secretion of the
      latter then dropped to levels lower than those observed in control mice.
      Treatment with MTX reversed levels of the cytokines to levels observed in healthy
      mice, IL-4 and IL-10, the Th2 type cytokines, predominated later in disease
      course, 5 months after immunization. Two to 3 months later production of IL-4
      dropped to levels lower than those of control mice. IL-10 secretion remained
      higher than in controls throughout the experiment. The production of both IL-4
      and IL-10 in MTX treated mice was also similar to that of control mice.
      CONCLUSION: The restoration of the cytokine profile to normal levels observed in
      the MTX treated mice from the initial steps of disease induction suggests its
      beneficial effects in SLE might be mediated through modulation of cytokine
      production.

PMID- 9195513
TI  - High prevalence of antiphospholipid antibodies in patients taking procainamide.
AB  - OBJECTIVE: To determine whether antiphospholipid antibodies (aPL) are more
      prevalent in cardiac patients taking procainamide than in a control population of
      similar elderly cardiac patients and to determine whether these antibodies react
      in an ELISA in which the primary antigen is beta 2-glycoprotein I (beta 2-GPI).
      METHODS: aPL and antibodies to beta 2-GPI were measured in 66 patients taking
      procainamide from a Veterans Administration Medical Center population and a
      control group of 30 similar cardiac patients not taking procainamide. RESULTS:
      21% of the patients taking procainamide and no control patients were found to
      have moderate to high aPL. There were similar results in an assay that measured
      anti-beta 2-GPI in the absence of exogenous phospholipids. aPL were associated
      with antinuclear antibodies and antihistone antibodies but not with diabetes or
      clinical manifestations of drug related lupus. There was no increase in
      cholesterol or past thrombotic history associated with aPL, but there was a
      frequent history of noncardiac thrombosis in patients taking procainamide
      (25.7%). CONCLUSION: The predictive significance of procainamide induced aPL
      remains unknown but beta 2-GPI dependent aPL may be of some concern in this
      elderly population already at high risk for thrombosis.

PMID- 9195514
TI  - Salivary and serum interleukin 6 in primary Sjogren's syndrome.
AB  - OBJECTIVE: To measure interleukin 6 (IL-6) salivary and serum concentrations in
      primary Sjogren's syndrome (SS), to correlate these data with the clinical
      presentation in patients, and to determine if salivary IL-6 is reflective of
      local exocrine involvement or of the underlying autoimmune disorder. METHODS:
      Thirty-one patients with primary SS, 15 with primary biliary cirrhosis (PBC), and
      14 healthy controls were studied. Parotid secretion was stimulated with 2% citric
      acid and collected using a Carlson-Crittenden collector. Concentrations of
      salivary and serum IL-6 were determined using a high sensitivity ELISA. Serologic
      autoimmune disease markers and salivary functional and histopathologic disease
      markers in the patients with SS were correlated with salivary and serum IL-6
      levels. RESULTS: Mean serum IL-6 concentrations were elevated in both patient
      groups (SS = 3.05 pg/ml, PBC = 3.07 pg/ml, healthy subjects = 0.843 pg/ml). Mean
      stimulated salivary IL-6 concentrations were elevated only in the patients with
      SS (16.21 pg/ml) compared to the PBC (1.07 pg/ml) and healthy subjects (0.769
      pg/ml). No correlation was found between serum and salivary IL-6 concentrations
      for any group. Positive correlations were found between salivary IL-6
      concentrations and serum IgG concentrations and between salivary IL-6 and
      erythrocyte sedimentation rate. Higher IL-6 concentrations were associated with
      increased disease activity. CONCLUSION: Salivary IL-6 concentration is elevated
      in SS compared to healthy subjects and patients with another systemic autoimmune
      disease without salivary gland involvement. Elevated salivary IL-6 concentrations
      in SS are reflective of local exocrine involvement and may serve as a useful
      monitor of disease activity.

PMID- 9195515
TI  - Nested polymerase chain reaction strategy simultaneously targeting DNA sequences
      of multiple bacterial species in inflammatory joint diseases. I. Screening of
      synovial fluid samples of patients with spondyloarthropathies and other
      arthritides.
AB  - OBJECTIVE: Bacteria play a crucial pathogenetic role in Lyme arthritis (LA),
      reactive arthritis (ReA), other forms of spondyloarthropathy (SpA), and possibly
      in undifferentiated oligoarthritis (uOligo). Polymerase chain reaction (PCR)
      technology has been applied to detect bacterial DNA of individual microbes in
      synovial fluid (SF) of patients with arthritides. We screened for DNA sequences
      of 8 bacterial species simultaneously in SF of patients with inflammatory joint
      disease. METHODS: We examined 104 SF samples of 96 patients with ReA (n = 13),
      undifferentiated SpA (uSpA, n = 10), uOligo (n = 50), juvenile chronic arthritis
      (JCA, n = 13), and rheumatoid arthritis (RA, n = 10). A nested PCR approach was
      developed to detect DNA sequences of 8 bacteria: Chlamydia trachomatis, C.
      pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter
      jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi. The
      detection limit was determined at 10 bacterial/sample. Serology and lymphocyte
      proliferation assay were done in parallel in most patients. RESULTS: In 12 cases
      bacterial DNA of B. burgdorferi (n = 7), C. trachomatis (n = 2), C. jejuni (n =
      2), and C. pneumoniae (n = 1) was detected in patients with uOligo (n = 9) and
      JCA (n = 3), while no evidence of bacterial DNA was found in patients with ReA,
      uSpA, and RA. Shigella flexneri DNA was detected in 4 cases, but the significance
      of this finding remains uncertain due to the high sequence homology of this
      species with Escherichia coli. DNA of Y. enterocolitica, S. enteritidis, or K.
      pneumoniae was not found. A positive serologic response was found in 7/9 PCR
      positive patients. In 11/96 cases antibodies to 2 or more bacteria were found in
      parallel (11.5%). Antigen specific lymphocyte proliferation was observed in 5/9
      PCR positive patients. CONCLUSION: Bacterial DNA was detected in peripheral joint
      of patients with uOligo and JCA, but not in ReA, uSpA, or RA in this study. The
      detection of bacterial DNA in synovial material by PCR technology gives useful
      diagnostic information, especially when antibodies against several microbes are
      present or antibodies are not detectable. Failure to detect bacterial DNA in
      patients with ReA and uSpA with longstanding disease suggests that in later
      stages autoimmune mechanisms may operate.

PMID- 9195516
TI  - Nested polymerase chain reaction strategy simultaneously targeting DNA sequences
      of multiple bacterial species in inflammatory joint diseases. II. Examination of
      sacroiliac and knee joint biopsies of patients with spondyloarthropathies and
      other arthritides.
AB  - OBJECTIVE: Bacteria play a crucial pathogenetic role in reactive arthritis (ReA)
      and other forms of spondyloarthropathy (SpA) and in Lyme arthritis. Although
      there is evidence of local persistence of bacterial antigens no definitive method
      revealing microbes in peripheral joints has been established. We detected DNA of
      individual bacteria in synovial material by PCR. Applying molecular technology we
      screened simultaneously for 8 bacterial genomes in arthritis and sacroiliitis.
      METHODS: Sacroiliac (SI) biopsy specimens taken from the SI joint of 8 patients
      with ankylosing spondylitis (AS, n = 5) and undifferentiated SpA (uSpA, n = 3) by
      computed tomography guided biopsy were investigated for presence of bacterial
      DNA. Similarly, synovial membrane samples obtained by office arthroscopy from 15
      patients with ReA (n = 5), uSpA (n = 3), undifferentiated oligoarthritis (uOligo,
      n = 3), and rheumatoid arthritis (RA, n = 4) were screened. Nested PCR was
      performed for DNA of the following bacteria: Chlamydia trachomatis, C.
      pneumoniae, Yersinia enterocolitica, Salmonella enteritidis, Campylobacter
      jejuni, Shigella flexneri, Klebsiella pneumoniae, and Borrelia burgdorferi.
      RESULTS: No bacterial DNA was found in the SI biopsies of patients with uSpA and
      AS. DNA of B. burgdorferi (n = 2) and C. trachomatis (n = 1) was detected in 3
      patients with uOligo, but not in patients with ReA or RA. DNA of other microbes
      including K. pneumoniae was not found. Patients' mean disease duration was 5.3
      years (2 mo-8.4 yrs). CONCLUSION: We found bacterial DNA in peripheral joints of
      patients with uOligo, while in patients with ReA, AS, and uSpA no bacterial DNA
      was detected in peripheral or SI joints. The failure to detect bacterial DNA in
      patients with SpA suggests autoimmune mechanisms operate in later stages of
      disease.

PMID- 9195517
TI  - Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic
      arthritis.
AB  - OBJECTIVE: To identify isolated peripheral enthesitis and/or dactylitis as a
      subset of psoriatic arthritis (PsA) and to define the clinical characteristics of
      these patients. METHODS: We examined 401 unselected patients with PsA seen in 3
      Italian rheumatological centers over a 6 month period. The diagnosis of PsA was
      based upon the clinical experience of a rheumatologist. The clinical features of
      patients with PsA were assessed by clinical examination and review of the
      patients' charts, evaluating the presence of peripheral arthritis, spinal
      involvement, dactylitis, and enthesitis. A series of 483 rheumatological patients
      without psoriasis and spondyloarthropathy (European Spondylarthropathy Study
      Group criteria) seen consecutively in a one month period constituted the control
      group. RESULTS: 14 patients (3.5%) presented isolated episodes of peripheral
      enthesitis and/or dactylitis. No patient developed peripheral arthritis and/or
      axial involvement during the followup period (median 30 mo; range 3-72 mo). 10/14
      patients (71%) presented at least one episode of finger and/or toe dactylitis. 5
      of these 10 patients (50%) had additional episodes of peripheral enthesitis
      (Achilles tendinitis, plantar fasciitis, and posterior tibial tendinitis).
      Episodes of Achilles tendinitis and/or plantar fasciitis were present in 8/14
      patients (57%). 3 of these 8 patients (37%) had associated peripheral enthesitis
      in other sites as well: lateral epicondyle, insertion of the patella tendon into
      the inferior pole of the patella, femoral quadriceps, and posterior tibial
      tendons. An additional case had posterior tibial tendinitis and 2 episodes of toe
      dactylitis. None of these 14 cases presented radiological evidence of
      sacroiliitis and only one of the 13 typed was HLA-B27 positive. 12 patients
      (2.4%) of the control group had episodes of peripheral enthesitis (11 plantar
      fasciitis and one Achilles tendinitis). No patient had episodes of dactylitis.
      The frequency of isolated Achilles tendinitis and/or dactylitis was significantly
      higher in patients with PsA compared to controls (3.5 vs 0.2%; p = 0.001).
      CONCLUSION: In some patients PsA can occur only with peripheral enthesitis,
      particularly Achilles tendinitis, and/or dactylitis. These patients may represent
      a subset of PsA, not defined by Moll and Wright and spondyloarthritis
      classification criteria, and poorly recognized in the studies on PsA.

PMID- 9195518
TI  - HLA-B27 subtypes positively and negatively associated with spondyloarthropathy.
AB  - OBJECTIVE: Eleven subtypes of HLA-B27 have been identified. If some of these
      subtypes had a stronger association with spondyloarthropathy (SpA) than others,
      this might tell us which peptides are of pathogenetic importance. A subtype
      preponderance has not been proved in Caucasians or in Asian Indians. Our
      objective was to determine whether some subtypes are positively or negatively
      associated with SpA in Indonesia. METHODS: Cells of 34 HLA-B27 positive patients
      with SpA (fulfilling the European Spondylarthropathy Study Group criteria) and 26
      HLA-B27 positive controls, all living in Java, Indonesia, were sampled. Patients
      and controls were divided according to their presumed ethnic origin. HLA-B27
      subtyping (B*2701-09) was performed by polymerase chain reaction in combination
      with sequence specific oligonucleotide probes to analyze polymorphism in exons 2
      and 3 of HLA-B27. RESULTS: HLA-B*2701, *2702, *2703, *2708, and *2709 were found
      in neither group. HLA-B*2704 was found in 23/34 (68%) of the patients and in only
      4/26 (15%) of the controls (p < 0.01). HLA-B*2706 was found in none of the 34
      patients, but in 21/26 (81%) of the controls (p < 0.01). One drawback of the
      study was that most patients were of Chinese descent and most controls were
      native Javanese. Nevertheless, the absence of SpA among HLA-B*2706 positive
      individuals is noteworthy. CONCLUSION: HLA-B*2704 is positively associated with
      SpA (RR = 11.5), while *2706 is negatively associated with this disease (RR <
      0.007). The results confirm the findings of Lopez-Larrea, et al in Thailand.

PMID- 9195519
TI  - Synoviocyte proliferation in joints of SCID mice induced by toxic shock syndrome
      toxin-1 stimulated T cells from patient with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the histopathological arthropathy in severe combined
      immunodeficient (SCID) mice given intraarticular injection of toxic shock
      syndrome toxin-1 (TSST-1) stimulated T cells from patients with rheumatoid
      arthritis (RA). METHODS: Unstimulated or TSST-1 stimulated T cell blasts (TB
      TSST) of synovial fluid mononuclear cells from patients with RA (RASFMC) were
      intraarticularly injected into the knee joint of SCID mice. Four weeks later, the
      knee joints were histopathologically examined and the numbers of fibroblasts in
      the synovial tissues were compared with those of controls. Total RNA of the SCID
      mouse knee joints was isolated and Southern analysis for human T cell receptor
      (TCR) V beta 2 and human tumor necrosis factor-alpha (TNF-alpha) was carried out.
      RESULTS: Hyperplasia and increased numbers of the fibroblasts as well as
      neovascularization of the synovial tissues were observed in the SCID mouse knee
      joint tissues injected with TB-TSST of RASFMC compared with those injected with
      unstimulated T cells from RASFMC or with TB-TSST from peripheral blood of healthy
      controls. Messenger RNA for human TCR V beta 2 and TNF-alpha were detected in the
      SCID mouse knee joint tissues injected with TB-TSST from RASFMC. CONCLUSION:
      Superantigen TSST-1 stimulated T cells from RASFMC have the ability to induce
      chronic arthropathy with fibroblast proliferation and neovascularization in the
      SCID mouse.

PMID- 9195520
TI  - Interaction between cyclosporin A and nonsteroidal antiinflammatory drugs.
AB  - OBJECTIVE: Although cyclosporin A (CyA) has been shown in a series of controlled
      trials to be of benefit to patients with rheumatoid arthritis (RA), the majority
      of patients continue to require nonsteroidal antiinflammatory drugs (NSAID) for
      relief of joint pain and stiffness. Our aim was to determine whether there is a
      clinically important difference in calculated creatinine clearance when CyA is
      given concurrently with NSAID with high cyclooxygenase activity (indomethacin and
      ketoprofen) compared with sulindac, which has been claimed to have fewer renal
      effects than other NSAID, and compared with a simple analgesic, paracetamol.
      METHODS: Patients with RA started 2.5 mg/kg CyA/day and dosage was increased
      cautiously to 5 mg/kg/day or less if the serum creatinine rose by > or = 30%
      above baseline. The mean stabilized dose was 171.43 +/- 48.94 mg/day. Once CyA
      dose was stabilized, patients were allocated in random order to possible
      sequences of 4 week periods of acetaminophen, indomethacin, ketoprofen, and
      sulindac. Monitoring of cyclosporine levels, nephrotoxicity, and hepatoxicity,
      and adjustment of doses were by an "unblinded" clinician not in direct contact
      with study patients. All other assessments were made by a "blinded" clinician.
      Patients were instructed to take the identical appearing gelatin capsules qid.
      The multiple crossover design was analyzed using analysis of variance procedures
      for repeated measures. RESULTS: 35 patients were enrolled, of whom 32 patients
      completed the acetaminophen and at least one course of NSAID. The calculated
      creatinine clearance was increased by 2.79 ml/min (3.5%) on average for
      acetaminophen versus all 3 NSAID (6% for indomethacin, 2.3% for ketoprofen, 2.6%
      for sulindac). The study had adequate power to detect a true difference of more
      than 10% in mean creatinine clearance for each major comparison. CONCLUSION:
      NSAID studied did not produce a clinically important difference in the calculated
      creatinine clearance in these patients-the difference with acetaminophen was
      modest and not of clinical significance. There is no evidence that any of the 3
      NSAID studied have an advantage or disadvantage. It seems reasonable to allow
      patients to continue an NSAID of their or their clinician's choice.

PMID- 9195521
TI  - Intradermal urate tophi.
AB  - OBJECTIVE: To analyze the clinical features and identify risk factors associated
      with the development of intradermal urate tophi. METHODS: Six patients (5 men and
      1 woman, mean age 59.8 yrs) with intradermal tophi were studied between 1987 and
      1996. RESULTS: Intradermal urate crystal deposits appeared as small, superficial,
      pustule-like, whitish lesions. All patients experienced superimposed inflammatory
      episodes with increasing pain, swelling, and erythema of the intradermal tophi.
      In one patient, the lesions were associated with a peculiar skin
      hyperpigmentation. Five had intermittent liquefaction and ulcerations of the
      lesions with drainage of white chalky matter from which monosodium urate crystals
      were recovered. Mean pre-treatment serum urate was 570.6 mumol/l (range 496-720).
      Risk factors for gout and intradermal tophi included renal failure in all 6,
      hypertension and chronic diuretic therapy in 4, and one patient each with alcohol
      abuse, chronic low dose acetylsalicylic acid, myeloma, and a positive family
      history. CONCLUSION: Intradermal urate tophi with superimposed inflammatory
      episodes, intermittent ulcerations, and possibly pigmentary changes, are rare
      skin manifestations of chronic tophaceous gout. Renal insufficiency,
      hypertension, and chronic diuretic use are factors associated with the
      development of hyperuricemia and gout in these patients.

PMID- 9195522
TI  - Aspirin and nonsteroidal antiinflammatory drug use in elderly women: effects on a
      marker of bone resorption. The Study of Osteoporotic Fractures Research Group.
AB  - OBJECTIVE: Epidemiological studies suggest nonsteroidal antiinflammatory drug
      (NSAID) and aspirin use is associated with a modest increase in bone mineral
      density of the hip and lumbar spine. The ability of NSAID to block prostaglandin
      E2 production has been shown to impair osteoclast activity in animal models. To
      determine if regular use of these compounds inhibits bone resorption, we assessed
      NSAID or aspirin use and N-telopeptide crosslink excretion in elderly
      postmenopausal women. METHODS: N-telopeptide crosslink excretion was assessed
      from a consecutive sample of 499 women from the Study of Osteoporotic Fractures,
      age > 65 years, who provided a morning urine sample. Questionnaire, examination,
      and bone mineral density data were obtained at the same visit. RESULTS: In
      unadjusted models, daily use of NSAID or aspirin was associated with a reduction
      of 12.5% (95% CI 0.5, 24.5) in N-telopeptide crosslink excretion (p < 0.05).
      After adjustment for potential confounders, N-telopeptide crosslink excretion was
      -4.8% (95% CI -24.4, 14.8) in NSAID users and +7.6% (-9.3, 24.5) in aspirin users
      compared to nonusers. CONCLUSION: Regular use of either NSAID or aspirin by
      elderly women was not associated with reduction in N-telopeptide crosslink
      excretion compared to nonusers.

PMID- 9195523
TI  - Comparative effects of nabumetone, sulindac, and ibuprofen on renal function.
AB  - OBJECTIVE: Nonsteroidal antiinflammatory drugs (NSAID) have been associated with
      hemodynamically mediated acute renal failure. There appear to be differences
      among NSAID in producing this effect. We compare renal effects of ibuprofen,
      sulindac, and nabumetone. METHODS: Seventeen women over age 56 receiving
      hydrochlorothiazide and fosinopril for hypertension who had osteoarthritis
      requiring NSAID received 3 different NSAID to evaluate potential varying renal
      effects. In an investigator blinded randomized study, patients received
      nabumetone, sulindac, or ibuprofen for 1 month with intervening 2 week control
      periods. After each period renal function was assessed by inulin and para
      aminohippurate clearances and urinary prostaglandins were measured. RESULTS: No
      overall statistical differences among the NSAID were observed. However, there
      were clinically meaningful differences during ibuprofen therapy: 4 patients
      developed a clinically significant decrease in renal function; during sulindac
      therapy one of these also developed a clinically significant decrease in renal
      function. During nabumetone there were 0 episodes of clinically significant
      decrease in renal function. Using Gomez equations, glomerular hydrostatic
      pressure and afferent and efferent arteriolar resistances were estimated. None
      changed overall during any intervention. However, the 4 patients who developed
      decreased renal function while taking ibuprofen were analyzed separately.
      Glomerular hydrostatic pressure decreased 15%; afferent arteriolar resistance
      increased 85%. These changes were associated with marked decreases in
      vasodilatory prostaglandins compared to patients receiving ibuprofen who did not
      develop decreases in renal function. CONCLUSION: There are differences in effect
      on renal function among NSAID. These can be correlated with specific alterations
      in suppression of the cyclooxygenase system cascade and related to changes in the
      hemodynamic control of glomerular filtration.

PMID- 9195524
TI  - The serine proteinase inhibitor antileukoproteinase specifically accumulates in
      normal but not in arthritic cartilage.
AB  - OBJECTIVE: To investigate whether the serine proteinase inhibitor
      antileukoproteinase (aLP) specifically accumulates in articular and
      extraarticular cartilage in normal and arthritic rats after intravenous (i.v.)
      injection. METHODS: [123I] or [125I] radiolabeled aLP and a control protein of
      comparable size were injected iv into normal rats or rats with chronic, antigen
      induced arthritis (AIA). Joint accumulation of the 2 proteins was followed by
      scintigraphy and organ tissue radioactivity was assessed by autoradiography and
      well counter measurements. Immunoprecipitation of aLP from articular cartilage
      was also performed and the content of charged molecules in normal and arthritic
      cartilage determined using toluidine blue staining. RESULTS: The accumulation of
      both radiolabeled aLP and control protein in the normal joint was clearly
      detectable by scintigraphy, with significant differences between the 2 proteins.
      In accordance with the scintigraphic data, direct tissue radioactivity
      measurements, immunoprecipitation, and autoradiography showed highly specific
      accumulation of radiolabeled aLP in articular and extraarticular cartilage of
      normal rats. The specific accumulation of aLP in articular cartilage was lost in
      rats with AIA in parallel with a loss of charged matrix molecules. CONCLUSION:
      I.v. injected serine protease inhibitor aLP specifically accumulates in articular
      and extraarticular cartilage of normal rats. This physiological pathway of
      cartilage accumulation, lost in proteoglycan depleted arthritic cartilage, may
      serve to maintain the local balance between proteinase function and inhibition.

PMID- 9195525
TI  - Gene expression of collagen types IIA and IX correlates with ultrastructural
      events in early osteoarthrosis: new applications of the rabbit meniscectomy
      model.
AB  - OBJECTIVE: To examine the phenotypic expression and geographic distribution of
      collagens in early stages of osteoarthrosis and their relationship to
      ultrastructural events in cartilage. METHODS: In situ hybridization was used to
      localize articular expression of total type II (A+B) and type IX collagen at 2
      and 4 weeks in the rabbit meniscectomy model of osteoarthrosis. The expression of
      the developmental marker collagen IIA was analyzed at the same time points.
      Articular cartilage structure was examined by scanning electron microscopy.
      RESULTS: Little difference was found in total type II or type IX collagen gene
      expression for operated versus control limbs at 2 weeks. Gene expression for
      collagen types IIA and IX was found to be site-specific by the 4 week period and
      was largely limited to the meniscectomy site. At 4 weeks, this activity was
      correlated with site-specific alterations in chondrocyte morphology, qualitative
      changes in the collagen matrix, and articular surface delamination on microscopy.
      CONCLUSION: Gene expression for collagen types IIA and IX is site-specific and
      correlates with ultrastructural changes in cartilage in this model of early
      osteoarthrosis. We present the first known report of the distribution of type IX
      collagen gene expression in any model of osteoarthrosis. These findings support
      the central importance of matrix interactions in osteoarthrosis and suggest that
      early phases of repair involve re-expression of a developmental sequence by
      chondrocytes.

PMID- 9195526
TI  - Risk factors for osteoarthritis in the tibiofemoral and patellofemoral joints of
      the knee.
AB  - OBJECTIVE: Risk factors for osteoarthritis (OA) in the different compartments of
      the knee are important in the pathogenesis of knee OA. We examined the risk
      factors associated with OA of the tibiofemoral and patellofemoral compartments of
      the knee. METHODS: A population-based study of 325 unrelated, middle aged females
      was performed. Knee and hand radiographs for each individual were graded for
      joint space narrowing and osteophytes using a standard atlas. Individuals with
      knee OA were classified as having tibiofemoral OA only, patellofemoral OA only,
      or a combination of both tibiofemoral and patellofemoral OA. Information on risk
      factors was obtained by a structured interview and examination. RESULTS: Obesity
      was associated with all the categories of knee OA. This relationship was
      strongest for the combined tibiofemoral and patellofemoral OA [OR (95% CI) = 7.26
      (2.36-22.31) for the highest vs lowest third]. There was a strong association
      between distal interphalangeal OA and isolated tibiofemoral OA [OR = 6.67 (1.94
      22.94)], but no association with patellofemoral OA. There was an inverse
      association between premenopausal status and patellofemoral OA [OR = 0.23 (0.06
      0.84)]. CONCLUSION: The pathogenetic mechanisms involved in patellofemoral and
      tibiofemoral OA may differ; clarification of the etiology of OA for the separate
      compartments of the knee is needed.

PMID- 9195527
TI  - Prospective use of intramuscular triamcinolone acetonide in pseudogout.
AB  - OBJECTIVE: To prospectively assess the efficacy of intramuscular (i.m.)
      triamcinolone acetonide in the treatment of pseudogout. METHODS: Fourteen
      patients with crystal proven pseudogout presenting with an acute attack within 5
      days of onset were treated with intramuscular triamcinolone acetonide 60 mg and
      followed for 30 days. Patients with inadequate response were eligible for a 2nd
      triamcinolone acetonide injection on Day 1-2. RESULTS: Twelve patients had
      contraindication to nonsteroidal antiinflammatory agents (NSAID). Acute arthritis
      was monoarticular in 10 patients, and involved 2 or more joints in 4 patients.
      All patients had good clinical response to triamcinolone acetonide based on
      restoration of near baseline joint range of motion and joint circumference, and
      at least 50% improvement in patient and physician global assessment. Major
      clinical improvement occurred by Day 1-2 (2 patients), Day 3-4 (11 patients), and
      Day 10-14 (one patient). Six patients required a 2nd triamcinolone acetonide
      injection on Day 1-2. Toxicities were not observed. CONCLUSION: I.m.
      triamcinolone acetonide appears to be safe, well tolerated, and effective in the
      treatment of pseudogout. It may be a reasonable alternative therapy when NSAID
      are contraindicated, and for polyarticular attacks where intraarticular
      corticosteroids are impractical.

PMID- 9195528
TI  - Work and disability status of persons with fibromyalgia.
AB  - OBJECTIVE: To determine the prevalence and determinants of self-reported work
      disability in persons with fibromyalgia (FM). METHODS: A longitudinal,
      multicenter survey of 1604 patients with FM from 6 centers with diverse
      socioeconomic characteristics was begun in 1988. Assessments were by self-report
      questionnaire and telephone contact, and included work and disability events that
      occurred before and after 1988. Comparative analyses were performed on the entire
      data set and, separately, on the Wichita data set. RESULTS: More than 16% of
      patients reported receiving US Social Security disability (SSD) payments (highest
      center rate 35.7%; lowest center rate 6.3%) compared to 2.2% of the US population
      (US Social Security Administration data) and 28.9% of patients with rheumatoid
      arthritis seen at the Wichita outpatient rheumatology clinic. Overall, 26.5%
      reported receiving at least one form of disability payment when SSD and other
      sources of disability payments were considered. In Wichita, less than 25% of SSD
      awards were made specifically for FM, but after 1988 that figure increased to
      46.4%. Work disability was greatest at the San Antonio and Los Angeles centers.
      Multivariate predictors (correlates) included pain, Health Assessment
      Questionnaire disability, and unmarried status. In addition, more than 70% of
      patients reporting being disabled did receive disability payments. On the other
      hand, 64% reported being able to work all or most days, and more than 70% were
      employed or were homemakers. CONCLUSION: Although most patients (64%) report
      being able to work, we found high rates of self-reported work disability awards
      among persons with FM followed in 6 rheumatology centers. But we also found great
      variability among centers as to awards and as to self-reported work ability.
      Center differences in work disability might reflect clinic referral patterns,
      physician beliefs, or socioeconomic status.

PMID- 9195529
TI  - Evidence for RANTES, monocyte chemotactic protein-1, and macrophage inflammatory
      protein-1 beta expression in Kawasaki disease.
AB  - OBJECTIVE: Patients with Kawasaki disease mount an immune response directed to
      their abnormally stimulated vascular endothelium, that is associated with
      vascular inflammation and injury and a predisposition to arterial aneurysm
      formation. This suggests that specific pro-inflammatory cytokines may mediate
      these hyperreactive responses. The selective chemoattractant and activation
      effects of chemokines on lymphocytes identifies them as potential candidates in
      mediating selective inflammatory processes in Kawasaki disease. We examined
      peripheral blood from patients with Kawasaki disease for chemokine gene
      expression. METHODS: Consecutive samples from 14 patients during the acute,
      subacute, and convalescent phases of their illness were collected and elaborated
      for RANTES, macrophage inflammatory protein-1 beta (MIP-1 beta) and monocyte
      chemotactic protein-1 (MCP-1) expression. RESULTS: RANTES and MCP-1 gene
      expression levels were significantly elevated in 12 of the 14 patients, and MIP-1
      beta gene expression was elevated in 13 of the 14 patients. There was no obvious
      correlation between clinical phase of the disease and chemokine expression level,
      yet elevated expression levels were detected in all phases, including the
      convalescent phase, when laboratory evidence of lymphocyte activation has been
      shown to return to normal. Serial samples showed persistence or increased
      expression of chemokine genes into the convalescent phase in patients with
      coronary artery lesions. CONCLUSION: Chemokine mediated inflammatory events may
      persist in the convalescent phase of Kawasaki disease and may contribute to
      further risk of vascular endothelial cell injury, specifically coronary aneurysm
      formation.

PMID- 9195530
TI  - Patellar enthesopathy in childhood: a new clinical and radiographic observation.
AB  - Enthesitis occurs commonly in patients with seronegative spondyloarthropathies.
      The patella is frequently affected by enthesopathy, but overgrowth has not been
      reported as a manifestation of enthesitis in pediatrics. We describe 3 patients
      with seronegative enthesopathy and arthropathy syndrome and patellar overgrowth.

PMID- 9195531
TI  - Multiple bursitis in systemic sclerosis.
AB  - Bursitis is a common clinical entity usually induced by trauma and infection. It
      often occurs in inflammatory diseases such as gout and rheumatoid arthritis. We
      describe a patient with systemic sclerosis who developed multiple bursitis in the
      later stage of the disease.

PMID- 9195532
TI  - Anaphylactic shock induced by intraarticular injection of methylprednisolone
      acetate.
AB  - There are numerous reports of hypersensitivity reactions to corticosteroids.
      However, cases of anaphylactic shock after intraarticular injection of
      corticosteroids are exceedingly rare. We describe a case of anaphylaxis in a 31
      year-old woman after intraarticular injection of synthetic methylprednisolone
      acetate. Immediately after injection she developed sneezing, angioedema,
      tachycardia, and marked hypotension. She responded promptly to treatment with
      subcutaneous epinephrine. She had received uneventfully one intraarticular
      injection of the same compound 4 years earlier. Intradermal skin testing showed
      strong reactivity to methylprednisolone acetate suspension, moderate reactivity
      to hydrocortisone, and weak reactivity to betamethasone. Tests with
      dexamethasone, triamcinolone, lidocaine, latex and nonsteroid constituents of the
      injected suspension including polyethylene glycol, polysorbate 80, mono and
      dibasic sodium phosphate, and myristyl-gamma-picolinium chloride were negative.
      This patient had developed anaphylaxis due to methylprednisolone acetate alone.
      Although such events are very rare, it is advisable to keep injectable
      epinephrine in the offices of rheumatologists.

PMID- 9195533
TI  - Serum sickness after wasp venom immunotherapy: clinical and biological study.
AB  - We describe a case of a man who developed serum sickness during wasp venom
      immunotherapy. Remarkable features were unusually severe neurological symptoms,
      multiple relapses in the absence of rechallenge, parallel course between clinical
      symptoms, serum levels of specific reagins and their antibodies, and a dramatic
      response to plasma exchange therapy. Desensitization is widely used and can cause
      a wide range of adverse effects; however, systemic vasculitis is a very rare
      complication and we are not aware of any case similar to ours, with serum
      sickness after injection of highly purified hymenoptera antigen. Clinicians
      should be aware of such a possibility.

PMID- 9195534
TI  - Microscopic polyangiitis after influenza vaccination.
AB  - We describe a case of microscopic polyangiitis involving skin and joints after
      influenza vaccination. Titers of antiinfluenza A antibody were markedly elevated
      in synovial fluid (SF) relative to those in serum. Antiinfluenza B antibodies
      were not present in SF but were present in serum, suggesting a reaction
      specifically involving antiinfluenza A antibodies localized to the affected
      joint. A review identified 16 other cases of vasculitis after influenza
      vaccination. The cases reclassified according to the Chapel Hill diagnostic
      criteria identified multiple forms of vasculitis including 7 other cases of
      microscopic polyangiitis. Three patients had similar illnesses after previous
      influenza vaccination or influenza-like illness. As in our case 11 cases resolved
      without recurrence. While this does not provide conclusive evidence that the
      vaccination caused the vasculitis, together with the serologic data we present it
      supports this hypothesis.

PMID- 9195535
TI  - Erythema elevatum diutinum with extensive acro-osteolysis.
AB  - Erythema elevatum diutinum (EED) is a rare chronic skin disease with cutaneous
      vasculitis, characterized by the absence of systemic vasculopathy. We describe a
      79-year-old white woman who has been followed with the diagnosis of EED for 27
      years. Our patient has a previously unreported combination of EED and acro
      osteolysis. After reviewing possible reasons for the association, her vasculitis
      seems the most likely factor.

PMID- 9195536
TI  - Implications of OMERACT outcomes in arthritis and osteoporosis for cochrane
      metaanalysis.
AB  - The Cochrane Collaboration has established a set of methods for pooling multiple
      studies assessing the same intervention. Assessing the same endpoints in all
      studies is important to allow different trials to be combined using metaanalysis.
      OMERACT can play a key role in establishing consensus on the use of common
      endpoints that are credible to clinicians. We describe the data that need to be
      included in individual trial reports for metaanalyses to be carried out.

PMID- 9195537
TI  - Definition and diagnosis of vertebral fracture.
AB  - The majority of vertebral deformities are asymptomatic and thus definition is
      normally based on radiographic appearance. There are no internationally agreed
      criteria for vertebral fracture based on radiographic appearance. A variety of
      morphometric methods have been developed to ascertain changes in vertebral shape
      based on a reduction in vertebral height. Criteria have to be established to
      determine what cutoff constitutes abnormality. An alternative is to adopt a
      semiquantitative grading using clinical observations of a experienced
      radiologist. This approach enhances specificity by excluding nonosteoporotic
      causes of changing vertebral shape. Such methods, however, may be subject to
      difficulties in standardization.

PMID- 9195538
TI  - Assessment of vertebral fractures in osteoporosis research.
AB  - The evaluation of conventional radiographs of the spine for vertebral fractures
      is an important component of clinical practice and research in osteoporosis.
      Aside from the traditional approach of qualitative assessment of spinal
      radiographs 2 additional approaches have evolved, particularly for applications
      in clinical research and epidemiological studies. The first is quantitative
      morphometry (QM), which is based upon measurement of 4-10 points on the lateral
      projection of the vertebral body and determination of vertebral heights and
      ratios of heights. QM is a definable, describable, and relatively reproducible
      method for detecting both prevalent and incident fractures. However, projectional
      effects substantially influence the reliability of these measures performed in
      isolation. Therefore, there has been renewed interest in the visual assessment of
      fractures using a semiquantitative assessment (SQ) grading scale with definable,
      morphological and morphometric criteria. This second approach, while perhaps not
      as objective as QM, makes use of all the information regarding vertebral size and
      shape and is fundamentally more complex. When performed with adequate training,
      however, it provided good reproducibility and reliability. This overview provides
      a brief analysis of the methodologies and the advantages and disadvantages of the
      QM and SQ approaches, and compares their relative performance, alone or combined,
      in a large prospective population based study.

PMID- 9195540
TI  - Quality of life measurement in osteoporosis.
AB  - Quality of life measurement may be helpful in randomized clinical trials in
      osteoporosis to assess therapeutic tradeoffs and compare effects of different
      interventions. Quality of life measures include generic measures, disease
      targeted measures, and performance based measures. Disease targeted measures
      increase the coverage of domains that are of particular importance to the patient
      with established osteoporosis. Several disease targeted measures are currently
      available. These measures show discriminant validity, but data on longitudinal
      responsiveness and validity in randomized clinical trials are not yet available.

PMID- 9195539
TI  - The value of biochemical markers of bone turnover in osteoporosis.
AB  - A number of biochemical markers of bone turnover have been described and these
      reflect the activity of osteoblasts (bone formation) or osteoclasts (bone
      resorption). These markers have the following advantages for the measurement of
      bone turnover: (1) they are noninvasive; (2) inexpensive; (3) can be repeated on
      many occasions; (4) and reflect bone cell activity in the entire skeleton. They
      have disadvantages: (1) they do not provide information about the work of
      individual cells; (2) they do not reflect the process of mineralization; and (3)
      their levels may be affected by the rate of clearance. The markers have been used
      to study the pathogenesis of osteoporosis, identify postmenopausal women with
      accelerated bone loss, predict fracture independently of bone loss, predict
      response to therapy, and monitor response to therapy. They may also be useful in
      the setting of clinical trials for choosing minimal and maximal effective doses,
      understanding the mechanism of the changes in bone mineral density (BMD) and
      studying the effect and time course of changes in bone after cessation of
      therapy. Markers do not provide a surrogate for fracture risk or BMD. However,
      they do have uses in osteoporosis and can provide preliminary data in the short
      term that can be used in the design of longterm studies of BMD and fracture.

PMID- 9195541
TI  - Osteoporosis clinical trials endpoints: candidate variables and clinimetric
      properties.
AB  - We reviewed evidence on endpoints used in osteoporosis clinical trials to assist
      in the development of a set of endpoints to be included in all trials. A MEDLINE
      search was conducted using the Cochrane Collaboration strategy for each endpoint.
      Additional published literature was obtained from content experts. A proposed
      list of endpoints was developed after consultation with experts in the field.
      Each endpoint was evaluated with respect to validity, reproducibility,
      redundancy, and feasibility. We classified the endpoints into 2 major categories:
      clinical health status outcomes and intermediate endpoints, and for each endpoint
      we present current evidence from the literature as pertains to defined
      methodologic criteria. Multiple endpoints have been used in osteoporosis clinical
      trials, and an agreement on a core set of measures needs to be evidence based
      with an emphasis on validity, reproducibility, and feasibility and to satisfy
      clinical credibility.

PMID- 9195542
TI  - Responsiveness of endpoints in osteoporosis clinical trials.
AB  - The usefulness of an endpoint depends in part on its responsiveness to clinically
      important change. From existing randomized controlled trials, the responsiveness
      of endpoints currently employed in osteoporosis clinical trials were examined.
      The responsiveness is presented as the sample size per group needed to show a
      statistically significant difference. The large variation found means that
      careful attention needs to be given to the responsiveness of the population
      studied when estimating the sample size.

PMID- 9195543
TI  - Guidelines for osteoporosis trials.

PMID- 9195544
TI  - Hepatitis C infection presenting with rheumatic manifestations.

PMID- 9195545
TI  - Eosinophilia-myalgia syndrome: opportunities realized and missed.

PMID- 9195546
TI  - Neonatal antiphospholipid syndrome.

PMID- 9195547
TI  - Do appendectomy and tonsillectomy reduce the risk of rheumatoid arthritis?

PMID- 9195548
TI  - Scleroderma and eosinophilic fasciitis in patients taking fosinopril.

PMID- 9195549
TI  - Pleural sclerosis for the treatment of pneumothorax and pleural effusion.
AB  - Pleural sclerosis is indicated to obliterate the pleural space when one wants to
      prevent the recurrence of a spontaneous pneumothorax or the reaccumulation of a
      pleural effusion. Although many different agents ranging from antibiotics to
      antiseptics to antineoplastics to talc have been advocated, none is ideal. It is
      interesting that in the era when we are mapping the human genome, the agent most
      commonly used for pleurodesis is talc. Talc is very inhomogeneous, and the
      mechanisms by which it produces pleurodesis are unknown. In this review we will
      discuss the theory and mechanism of pleurodesis, the indications and
      contraindications for it, the advantages and disadvantages of the agents
      presently used for it, and our recommendations for the procedure.

PMID- 9195550
TI  - Characterization of surfactant subtypes of beractant and a synthetic peptide
      containing surfactant KL4 following surface area cycling and addition of
      fibrinogen.
AB  - Surfactant is not a homogeneous material and can be separated into subtypes.
      Subtype conversion is clinically important because it is thought to occur
      naturally and because surface activity varies depending on the subtype.
      Fibrinogen, a naturally occurring serum protein, is known to affect this
      conversion. In this study we studied two surfactants, beractant and KL4, to
      examine their subtype characteristics. Surface area cycling, an in vitro method,
      was used in conjunction with sucrose gradient ultracentrifugation to separate
      subtypes in both surfactants. Activity, expressed as minimum surface tension of
      these subtypes, was measured using a pulsating bubble surfactometer. The effect
      of fibrinogen on subtype conversion and subsequent change in activity was
      elucidated. Our results indicate that following surface area cycling, beractant
      and KL4 have different subtypes and different responses to fibrinogen. Cycling of
      beractant resulted in two bands, representing a heavy and a light subtype. In the
      presence of fibrinogen, cycling resulted in two separate heavy subtypes. Cycling
      of KL4 surfactant also yielded light and heavy subtypes. However, in the presence
      of fibrinogen, cycling of KL4 resulted in ultraheavy subtypes. These ultraheavy
      subtypes retained minimum surface tension comparable to that of native KL4
      surfactant. We conclude that these two surfactant preparations have different
      subtype conversions when subjected to surface area cycling and in the presence of
      fibrinogen. These conversions result in different activities toward lowering
      surface tension. We speculate that endogenous fibrinogen will also affect these
      two surfactants differently in vivo and thus affect their clinical effectiveness.

PMID- 9195551
TI  - Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in
      vitro.
AB  - This study quantifies the antioxidant function of ambroxol (2-amino-3,5-dibromo-N
      [trans-4-hydroxycyclohexyl]benzylamine) in vitro. Polymorphonuclear cells (PMN)
      and mononuclear cells were isolated from the blood of healthy volunteers (n = 46)
      to determine reactive oxygen species (ROS) by luminol-enhanced chemiluminescence.
      Ambroxol or the controls N-acetylcysteine (NAC), nacystelyn (NAL), glutathione
      (GSH), superoxide dismutase (SOD), catalase, and the combination of SOD/catalase
      were incubated for 1 or 2 h with zymosan-activated cells in vitro using
      concentrations ranging from 10(-6) to 10(-3) mol/liter. Reduction of ROS-mediated
      luminescence was similar within the cell types. Ambroxol (10(-4) mol/liter)
      reduced ROS about 75% (1-h incubation) and 98% (2-h incubation), respectively (p
      < 0.001). SOD and SOD/catalase, but not the H2O2-catalyzing substances (NAC, NAL,
      GSH, and catalase), reduced cellular ROS. This indicates that inflammatory cells
      predominantly generate O2-, which can be scavenged by ambroxol. The antioxidant
      function of ambroxol with increasing incubation time suggests additional cellular
      antiinflammatory properties of this substance. Our results indicate that good
      antioxidant function of ambroxol is related mainly to direct scavenger function
      of reactive oxygen metabolites such as O2-. However, an antioxidative effect of
      ambroxol may also be associated with the reduction of prooxidative metabolism in
      inflammatory cells. Concluding from this observation, and because of the well
      known high affinity of ambroxol for lung tissue, ambroxol may be an alternative
      in antioxidant augmentation therapy, particularly in pulmonary diseases
      characterized by an overburden of toxic oxygen metabolites.

PMID- 9195552
TI  - Methacholine dose-response slopes from maximal bronchial challenge tests in
      asthmatic children: methodological aspects.
AB  - To determine whether the slope of a maximal bronchial challenge test (in which
      FEV1 falls by over 50%) could be extrapolated from a standard bronchial challenge
      test (in which FEV1 falls up to 20%), 14 asthmatic children performed a single
      maximal bronchial challenge test with methacholine (dose range: 0.097-30.08
      mumol) by the dosimeter method. Maximal dose-response curves were included
      according to the following criteria: (1) at least one more dose beyond a delta
      FEV1 > or = 20%; and (2) a MFEV1 > or = 50%. PD20 FEV1 was calculated, and the
      slopes of the early part of the dose-response curve (standard dose-response
      slopes) and of the entire curve (maximal dose-response slopes) were calculated by
      two methods: the two-point slope (DRR) and the least squares method (LSS) in %
      delta FEV1 x mumol-1. Maximal dose-response slopes were compared with the
      corresponding standard dose-response slopes by a paired Student's t test after
      logarithmic transformation of the data; the goodness of fit of the LSS was also
      determined. Maximal dose-response slopes were significantly different (p <
      0.0001) from those calculated on the early part of the curve: DRR20% (91.2 +/-
      2.7 delta FEV1%. mumol-1) was 2.88 times higher than DRR50% (31.6 +/- 3.4 delta
      FEV1%. mumol-1), and the LSS20% (89.1 +/- 2.8% delta FEV1. mumol-1) was 3.10
      times higher than LSS50% (28.8 +/- 1.5% delta FEV1. mumol-1). The goodness of fit
      of LSS50% was significant in all cases, whereas LSS20% failed to be significant
      in one. These results suggest that maximal dose-response slopes cannot be
      predicted from the data of standard bronchial challenge tests.

PMID- 9195553
TI  - Involvement of tachykinins in endotoxin-induced airway hyperresponsiveness.
AB  - Inhaled endotoxin, lipopolysaccharide (LPS), has been shown to result in
      bronchial hyperresponsiveness (BHR) to endogenous bronchoconstrictive mediators
      such as histamine. To determine the role of sensory neuropeptides released from
      bronchopulmonary C-fibers in LPS-induced BHR, 24 guinea pigs were allocated
      randomly to the following four groups. Animals in Groups I and IV were challenged
      with intratracheal instillation of 100 microliters of saline vehicle, and those
      in Groups II and III with 1 mg of LPS (Escherichia coli, 0111:B4) in 100
      microliters of saline. Groups III and IV also received a high dose capsaicin
      (HDC) treatment to deplete tachykinins from C-fibers 1-2 weeks prior to the
      experiment. Animals were anesthetized and paralyzed, and total lung resistance
      (RL) and compliance (Cdyn) were measured continuously during the experiment. Dose
      responses of RL and Cdyn to histamine (0-8 micrograms/kg, intravenously) and
      capsaicin (0-1.6 micrograms/kg, intravenously), a specific C-fiber stimulant,
      were obtained prior to and at 1, 2, and 3 h following LPS/saline vehicle
      challenge. At 2 h after LPS, delta RL caused by histamine (8 micrograms/kg) was
      significantly higher in Group II (1.145%) than that in Group I (280%; p < 0.05);
      similarly, delta RL caused by capsaicin (1.6 micrograms/kg) was also increased
      after LPS (Group I, 107%; Group II, 267%; p < 0.05). Although HDC treatment
      completely abolished the bronchomotor response to capsaicin in both Groups III
      and IV, it enhanced the LPS-induced BHR to histamine (8 micrograms/kg; Group III,
      1.834%; p < 0.05). In conclusion, these results suggest that the role of
      tachykinins in LPS-induced BHR may be dependent upon the type and the route of
      administration of the bronchoactive substance studied.

PMID- 9195554
TI  - Neopterin, beta 2-microglobulin, and acute phase proteins in HIV-1-seropositive
      and -seronegative Zambian patients with tuberculosis.
AB  - Neopterin is a biochemical marker for the activation of the cell-mediated immune
      system. We measured neopterin, beta 2-microglobulin, and acute phase proteins in
      31 HIV-seropositive and -seronegative Zambian patients with tuberculosis, using
      stored sera that had been obtained at the beginning and at end of
      antituberculosis treatment. In both HIV-seropositive and -seronegative patients
      neopterin and acute phase proteins were elevated when tuberculosis was initially
      diagnosed and fell during treatment. In contrast, the mean beta 2-microglobulin
      level increased during antituberculous therapy in the HIV-seropositive group.
      Serum neopterin levels at diagnosis were correlated with other parameters of
      disease activity (fever, anemia, and weight loss). In both groups, patients with
      persistently elevated neopterin levels at the end of treatment were more likely
      to suffer relapse of tuberculosis or other adverse health events in the
      subsequent follow-up period. Neopterin can be used to monitor the response to
      antituberculous therapy in both HIV-seropositive and -seronegative patients and
      may have a prognostic value for the patients' wellbeing in the follow-up period.

PMID- 9195555
TI  - Bronchial and bronchoalveolar inflammation in single early and dual responders
      after allergen inhalation challenge.
AB  - To characterize the cellular inflammation at the bronchial and bronchoalveolar
      levels, we evaluated 43 patients with asthma who were sensitized to house dust
      mites. On 2 consecutive days patients underwent methacholine challenge and
      allergen bronchial challenge. In addition, 6, 24, or 72 h after allergen
      challenge, fiberoptic bronchoscopy with bronchial lavage (BL) and bronchoalveolar
      lavage (BAL) was performed. Patients belonging to the 6-h, 24-h, or 72-h group
      were divided further into two subgroups: those with isolated early response to
      allergen (LAR-), and those with dual response to allergen (LAR+). The percentage
      of eosinophils and of epithelial cells in BAL fluid was significantly higher in
      LAR+ than in LAR- patients in the 6-h group (p < 0.05, each comparison), but not
      24 or 72 h after (p > 0.05, each comparison). Similarly, the proportion of BL
      eosinophils was also higher in LAR+ than in LAR- patients, both in the 6-h and in
      the 24-h group (p < 0.05, each comparison). In addition, increased proportions of
      BL neutrophils were present in the LAR+ patients belonging to the 24-h group (p <
      0.05). Comparing "proximal" = BL vs "distal" = BAL data, we found a significantly
      higher proportion of epithelial cells in BL compared with BAL, in both LAR- and
      LAR+ subjects, either 6, or 24, or 72 h after challenge (p < 0.01, each
      comparison) and increased percentages of BL neutrophils and eosinophils in LAR+
      patients (p < 0.05, each comparison), but not in LAR- patients, in the 24-h
      group. The percentages of BL or BAL macrophages and lymphocytes did not differ
      significantly among the different patient groups. These data indicate that the
      development of LAR after allergen inhalation challenge is associated with an
      early recruitment of eosinophils and with epithelial desquamation in the airways.
      In addition, after allergen challenge epithelial desquamation is more pronounced
      in the proximal than in the distal airways, independently of the type of
      bronchial response.

PMID- 9195556
TI  - Latitude, coastal or interior location and the evolution of the melanoma epidemic
      in the United States.
AB  - Estimates derived from linear models fitted to melanoma death rates at successive
      time periods for the contiguous states of the US suggest that, allowing for
      latitude, rates are higher in the coastal than in the interior states. The effect
      of latitude on melanoma death rates in the white population of the US is
      decreasing and will shortly be gone. This decrease is slower in the interior
      states than in the coastal ones. The deceleration of the rate change is most
      marked in the states with the highest rates, so that latitude may be regarded as
      a determinant of the initial rate for each state, while the subsequent change in
      rate is a function of that initial rate. Melanoma death rates appear to be
      stabilizing at levels that are unaffected by latitude.

PMID- 9195557
TI  - Effect of retinoic acid on melanoma cell-derived factor stimulation of fibroblast
      glycosaminoglycan synthesis.
AB  - The hyaluronan-rich matrix that surrounds many tumours and facilitates tumour
      cell growth and invasion is thought to be predominantly synthesized by normal
      stromal cells stimulated by tumour cell-derived factors. This study examines the
      possibility that the production of tumour cell-derived factors that stimulate
      fibroblast glycosaminoglycan (GAG) synthesis may be blocked by exposure to
      differentiation-inducing agents such as retinoic acid. We have demonstrated that
      Hs294T, C8161 and A375 human melanoma cell lines release factors into their
      medium that stimulate normal fibroblast GAG synthesis. Exposure of these melanoma
      cells to retinoic acid failed to mediate any significant reduction in growth over
      a 7-day period. Retinoic acid failed to block the tumour cell production of GAG
      stimulating activities and even enhanced the activities produced by the C8161
      cell line, particularly at low retinoic acid concentrations (48% stimulation at
      10(-9) M retinoic acid; P < 0.02). Addition of retinoic acid directly to
      fibroblast cultures exposed to fibroblast-conditioned medium resulted in an
      inhibition of GAG synthesis with a 33% inhibition observed at 10(-5) M. Addition
      of retinoic acid to fibroblast cultures exposed to the tumour cell-conditioned
      medium failed to inhibit the stimulation of GAG synthesis. Other differentiation
      inducing agents, such as hexamethylene-bis-acetamide and butyrate, also failed to
      block the production of tumour cell-derived GAG-stimulating activities. These
      results demonstrate that retinoic acid and other differentiation-inducing agents
      fail to inhibit melanoma cell production of fibroblast GAG synthesis-stimulating
      factors or their action upon fibroblasts.

PMID- 9195558
TI  - Investigation of oestrogen receptors, sex steroids and soluble adhesion molecules
      in the progression of malignant melanoma.
AB  - The question of whether melanoma tumours have classical oestrogen receptors (ERs)
      is unresolved, but epidemiological data clearly show a survival benefit for
      female patients with metastatic melanoma. The aims of this study were to examine
      to what extent the presence of ER in melanoma tumours might relate to disease
      progression and whether disease progression relates to patients' sex steroid
      status. Additionally, levels of two soluble adhesion molecules [circulating
      intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell
      adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic
      indicators of disease progression. ER immunocytochemical assay identified only
      two lesions (out of 69 investigated) which had any evidence of the receptors, and
      staining in these lesions was very modest. No significant changes in oestrone or
      androstenedione levels were noted for male or female patients with disease
      progression. As expected, oestradiol levels reflected the menopausal status of
      the female patients but, for all post-menopausal female patients and male
      patients, there was no significant relationship to tumour stage. However, a
      significant decrease in sex hormone-binding globulin occurred with disease
      progression in male but not female patients, and sex differences in the levels of
      soluble adhesion molecules were also seen in advanced metastatic disease.

PMID- 9195559
TI  - The melanoma-specific XMEL antigen is expressed in dysplastic naevi.
AB  - We have previously shown that a novel monoclonal antibody, XMEL, exhibited
      reactivity with deep primary melanomas while showing no reactivity with other
      tumours and normal tissue. XMEL was raised against a part of the extracellular
      domain of Xmrk, a growth factor receptor presumed to mediate melanoma formation
      in the Xiphophorus fish model. Here we investigate the range of XMEL
      immunohistochemical reactivity in paraffin sections from human common acquired
      and dysplastic naevi of both junctional and compound type. The strongest
      reactivity was observed with the compound dysplastic naevi. We conclude that the
      antigen recognized by XMEL acts early in the cascade of genetic alterations
      underlying progression into malignant melanoma. Our results also support the
      notion that the dysplastic naevus may play a role in progression of human
      malignant melanoma and may indeed represent the precursor stage.

PMID- 9195560
TI  - Superantigen-induced lysis of melanoma cells.
AB  - Superantigens like the Staphylococcus enterotoxin A (SEA) can direct cytotoxic T
      lymphocytes expressing certain T cell receptor V beta regions to lyse MHC class
      II-positive target cells. This superantigen-dependent cellular cytotoxicity
      (SDCC) has been extended to MHC class II-negative tumour cells by targeting T
      cells via conjugates of a tumour-specific monoclonal antibody (moAb) and a
      superantigen. In the present study the MHC class II-negative human melanoma cell
      lines G361 and MaRI were tested for susceptibility to SDCC in vitro. Antibodies
      recognizing the disialoganglioside GD3 and the CD10 antigen were linked to SEA
      either by a recombinant protein A-SEA fusion protein or an anti-kappa moAb-SEA
      chemical conjugate. Specific lysis of melanoma cells was dose- and effector to
      target (E:T) cell ratio-dependent. Introduction of a point mutation into the SEA
      gene (producing SEAm9) in order to reduce MHC II affinity of the superantigen,
      which has already been shown to severely diminish superantigen-dependent binding
      and lysis of MHC class II-positive cells, did not influence antibody-targeted
      SDCC. Cytotoxicity was equal with both antibodies (anti-GD3 and anti-CD10) and
      independent of whether protein A-SEA, protein A-SEAm9 or anti-kappa-SEA were
      used.

PMID- 9195561
TI  - Characterization of interleukin-1 alpha-induced melanoma cell motility:
      inhibition by type I and type II receptor-blocking monoclonal antibodies.
AB  - Interleukin-1 alpha (IL-1 alpha) induces cell motility in a variety of benign
      cell types and in some but not all malignant cell lines in vitro. This study
      characterizes the IL-1 alpha-induced motility of an aggressive human melanoma
      cell line that expresses both type I and type II IL-1 receptors. We tested the
      effect of monoclonal antibodies including function-blocking moAbs against the
      type I and type II IL-1 receptors on melanoma cell motility to determine which
      receptor is involved in signal transduction of IL-1 alpha-induced melanoma cell
      motility. IL-1 alpha significantly increases MM-RU melanoma cell migration in a
      dose-dependent manner using modified Boyden chamber assays at concentrations 10
      to 100 times less than concentrations that significantly inhibit cell growth.
      Computer-assisted time-lapse image analysis reveals that the motility is
      inhibited in a dose-dependent manner by neutralizing antibodies against IL-1
      alpha. Function-blocking monoclonal antibodies against either type I or type II
      IL-1 receptors show a significant inhibition of cytokine-induced enhanced cell
      migration. When both the anti-IL-1 receptor antibodies are added together, the
      motility-response is completely blocked to control levels. Taken together the
      data indicate that the IL-1 alpha-induced motility of MM-RU melanoma cells is
      mediated through both type I and type II IL-1 receptors. The significant
      inhibition of motility by neutralizing IL-1 alpha or blocking either one or both
      of the IL-1 receptors indicates an integration of IL-1-induced signals in the
      induction of melanoma cell migration.

PMID- 9195562
TI  - An immunohistochemical analysis of nm23 gene product expression in uveal
      melanoma.
AB  - Uveal melanoma is characterized by an unpredictable clinical course, during which
      metastatic disease may occur after a prolonged and, at present, undefinable
      disease-free interval. Because of its relative rarity and the dispersion of
      cases, the possible genetic alterations implicated in the invasive and metastatic
      behaviour of this ocular neoplasm have not yet been characterized. The aim of
      this immunohistochemical retrospective study was to assess the expression of nm23
      gene product, proposed to be a metastasis-suppressor gene, in uveal melanoma and
      to analyse its prognostic significance in relation to the various conventional
      histopathological parameters, currently considered the major prognostic
      indicators in this intra-ocular neoplasm. We analysed formalin-fixed paraffin
      embedded samples excised from 33 patients with uveal melanoma. Of these, 22 (67%)
      were positive for monoclonal antibody nm23. This nm23 positivity was inversely
      associated with scleral invasion level (P = 0.001) and largest tumour diameter (P
      = 0.02), which represent the two most significant prognostic factors for
      metastasis. On the other hand, there was no correlation between nm23 expression
      and other prognostic markers such as cell type, intraocular location or clinical
      characteristics. These results may suggest a close relationship between nm23 gene
      expression and metastatic potential of uveal melanomas. In addition, analysis of
      nm23 gene expression on bioptic tissue may represent an extreme useful prognostic
      tool for metastatic progression of uveal melanomas.

PMID- 9195563
TI  - An evaluation of tumour vascularity as a prognostic indicator in uveal melanoma.
AB  - Experimental and clinical evidence suggests that tumour angiogenesis plays a role
      in the tendency for certain neoplasms, including cutaneous melanomas, to
      metastasize. We evaluated whether tumour vasculature is associated with the rate
      of metastases in patients with melanoma of the choroid or ciliary body. The study
      was based on a group of 63 patients enucleated between 1976 and 1984 with
      paraffin-embedded tissue blocks available for sectioning and with known survival
      status as of December 1988. Vessel endothelial cells were highlighted with Ulex
      europaeus agglutinin I (UEA-I) conjugated with peroxidase. UEA-I-stained
      microvessels were counted at varying levels in the tumour (apex, centre and base)
      without knowledge of patient outcome. Patients with (n = 30) and without (n = 33)
      metastases had similar total vessel counts (P = 0.31). There was no evidence of
      greater vessel density in tumours that had metastasized, by level within the
      tumour. Similar results were obtained in multivariate analyses. Findings of this
      study suggest that tumour microvessel density is unrelated to patient survival in
      uveal melanoma.

PMID- 9195564
TI  - Simultaneous measurement of serum 5-S-cysteinyldopa, circulating intercellular
      adhesion molecule-1 and soluble interleukin-2 receptor levels in Japanese
      patients with malignant melanoma.
AB  - Serum 5-S-cysteinyl dopa (5-S-CD), circulating intercellular adhesion molecule-1
      (cICAM-1) and soluble interleukin-2 receptor (sIL-2R) have each been reported as
      useful markers for melanoma progression. To assess the clinical relevance of
      these three markers, we simultaneously assayed their serum levels in 30 Japanese
      melanoma patients. Pre-surgical serum levels of 5-S-CD, cICAM-1 and sIL-2R were
      elevated in six, 13 and five patients respectively. These abnormal values
      returned to normal after curative surgery in most of the patients, suggesting a
      direct relationship to the presence of the primary tumour. Pre-surgical values of
      these three markers, either individually or in combination, did not predict the
      development of subsequent metastases. The sequential measurements of the three
      markers in eight patients who had relapse after surgery showed that serum 5-S-CD
      is the most useful marker for disease progression, although it is dependent on
      the melanin-producing ability of individual recurrent tumours. sIL-2R seemed to
      reflect in vivo activation of the host immune system and was a good indicator for
      predicting occult metastasis in selected cases. Circulating ICAM-1 levels were
      less relevant to the clinical disease course in our cases, although they tended
      to increase strikingly after liver metastasis. Our results in this limited number
      of cases show that the significance of the three markers varied with the
      individual and suggest that the simultaneous measurement of these markers may
      facilitate the early detection of metastases and proper therapeutic intervention.

PMID- 9195566
TI  - Taking a ride on the information super highway ... and knowing when to get off.

PMID- 9195565
TI  - Melphalan dosing regimens for management of recurrent melanoma by isolated limb
      perfusion: application of a physiological pharmacokinetic model based on
      melphalan distribution in the isolated perfused rat hindlimb.
AB  - The optimal dosing schedule for melphalan therapy of recurrent malignant melanoma
      in isolated limb perfusions has been examined using a physiological
      pharmacokinetic model with data from isolated rat hindlimb perfusions (IRHP). The
      study included a comparison of melphalan distribution in IRHP under hyperthermia
      and normothermia conditions. Rat hindlimbs were perfused with Krebs-Hen-seleit
      buffer containing 4.7% bovine serum albumin at 37 or 41.5 degrees C at a flow
      rate of 4 ml/min. Concentrations of melphalan in perfusate and tissues were
      determined by high performance liquid chromatography with fluorescence detection.
      The concentration of melphalan in perfusate and tissues was linearly related to
      the input concentration. The rate and amount of melphalan uptake into the
      different tissues was higher at 41.5 degrees C than at 37 degrees C. A
      physiological pharmacokinetic model was validated from the tissue and perfusate
      time course of melphalan after melphalan perfusion. Application of the model
      involved the amount of melphalan exposure in the muscle, skin and fat in a
      recirculation system was related to the method of melphalan administration:
      single bolus > divided bolus > infusion. The peak concentration of melphalan in
      the perfusate was also related to the method of administration in the same order.
      Infusing the total dose of melphalan over 20 min during a 60 min perfusion
      optimized the exposure of tissues to melphalan whilst minimizing the peak
      perfusate concentration of melphalan. It is suggested that this method of
      melphalan administration may be preferable to other methods in terms of
      optimizing the efficacy of melphalan whilst minimizing the limb toxicity
      associated with its use in isolated limb perfusion.

PMID- 9195567
TI  - Myocarditis in Whipple's disease: an unsuspected cause of symptoms and sudden
      death.
AB  - Whipple's disease (WD) is an uncommonly diagnosed infection caused by the
      recently characterized bacillus, Tropheryma whippelii. The association of WD with
      pericarditis and endocarditis is widely recognized, although less attention has
      been paid to the myocardium as a site of disease. Although the disease was
      uniformly fatal before antibiotic therapy, current treatment usually results in
      cure. We report two patients whose deaths were directly related to cardiac
      involvement by WD and whose underlying disease escaped diagnosis for years. The
      first, a 60-year-old white woman, suffered a cardiovascular collapse, and
      lymphocytic myocarditis was demonstrated at autopsy. The second, a 48-year-old
      black man, had a lengthy history of progressive cardiac failure that terminated
      in arrhythmia. Extensive myocardial fibrosis, with lymphocytic and granulomatous
      inflammation, was demonstrated at autopsy. The presence of T. whippelii was
      confirmed by electron microscopic examination in both cases and by polymerase
      chain reaction in one. Patients with WD might harbor an undiagnosed lymphocytic
      or granulomatous myocarditis, and this diagnosis should be considered in the
      evaluation of cardiac failure.

PMID- 9195568
TI  - Vascular adrenal cysts: a clinicopathologic and immunohistochemical study of six
      cases and a review of the literature.
AB  - The clinical, histologic, and immunohistochemical features of six cases of
      hemorrhagic adrenal pseudocysts are reported together, with a review of the
      English literature on this topic since 1950. The mean age at presentation was 57
      years (range, 30-72 yr). There were four men and 2 women. The average cyst size
      was 9.2 cm (range, 6-16 cm). In four patients, the hemorrhagic adrenal
      pseudocysts were incidental findings. The remaining two patients presented with
      an abdominal mass and hypertension, respectively. The hemorrhagic pseudocysts
      were unilocular cystic masses surrounded by a fibrous capsule and containing
      abundant amorphous material, blood, and fibrin. Numerous dilated, thin-walled,
      vascular channels that stained strongly for Factor VIII-related antigen, collagen
      IV, laminin, Ulex europaeus agglutinin I lectin, and CD34 were present within the
      fibrous capsule, cyst contents, and surrounding residual adrenal gland. These
      findings support a vascular origin for these lesions, and they are thought,
      therefore, to be related to endothelial adrenal cysts. The literature review of
      111 vascular adrenal cysts (85 hemorrhagic pseudocystic type and 26 endothelial
      type) showed similar clinical features. The mean age at presentation was 44.5
      years (range, 5 d-95 yr), with a female predominance (62%). The most common
      clinical presentation was abdominal pain (35%), followed by incidental findings
      (32%). There were no significant clinical differences between hemorrhagic and
      endothelial type cysts. In some cases, the presence of intracystic islands of
      cortical cells can cause diagnostic confusion with adrenal cortical tumors. The
      presence, however, of a rich intracystic and capsular vascular network, normal
      appearing islands of cortical cells, and abundant thrombotic fibrinous material,
      rather than necrotic tumor cells, should rule out the possibility of a
      degenerating adrenal cortical neoplasm.

PMID- 9195569
TI  - Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study
      of 105 tumors.
AB  - Papillary renal cell carcinoma is the second most common carcinoma of the renal
      tubules and has been characterized genetically. Its morphologic features are
      incompletely characterized. It has been suggested that the presence of
      cytokeratin 7 is specific for papillary renal cell carcinoma. Collecting duct
      carcinoma might have papillary architecture, and it has been suggested that
      reaction with the Ulex europaeus lectin is specific for it. Sections from 105
      papillary renal cell carcinomas larger than 12 mm in diameter from 100 patients
      were studied, and immunohistochemical reactions were performed on 91. The tumors
      formed two morphologic groups. Type 1 (67 tumors) consisted of papillae and
      tubular structures covered by small cells with pale cytoplasm and characterized
      by small oval nuclei with inconspicuous nucleoli, frequent glomeruloid papillae,
      papillary edema, foamy macrophages in papillary cores, and psammoma bodies. Type
      2 (38 tumors) consisted of papillae covered by large cells with abundant
      eosinophilic cytoplasm and characterized by pseudostratification and large
      spherical nuclei with prominent nucleoli, glomeruloid papillae, psammoma bodies,
      edematous papillae, and foamy macrophages in papillary cores are uncommon. Type 2
      tumors were larger, more common in patients younger than age 40, and more
      frequently Stages 3 or 4 than were Type 1 tumors. Pseudocapsules were common in
      both and often were infiltrated by carcinoma. Sarcomatoid foci were found in five
      tumors. Eleven were stage T1, 54 T2, 23 T3, and 12 T4. Reaction for cytokeratin 7
      was strong or moderate in 48 of 61 Type 1 tumors, and reaction was null in 24 of
      30 Type 2 tumors. No tumor reacted with U. europaeus lectin.

PMID- 9195571
TI  - Clear nuclei of papillary thyroid carcinoma conspicuous in fine-needle aspiration
      and intraoperative smears processed by ultrafast papanicolaou stain.
AB  - The Orphan Annie-eyed clear nucleus, defined as a large, optically clear nucleus,
      devoid of chromatin strands, with sharp chromatin rim, is a more specific feature
      than are nuclear grooves or intranuclear cytoplasmic inclusions in papillary
      thyroid carcinoma. In addition, this characteristic nuclear feature is detectable
      at low magnification. Although these clear nuclei are routinely seen in paraffin
      sections, they are inconspicuously seen in conventionally processed touch
      imprints and fine-needle aspiration (FNA) smears. Among our two institutions,
      there have been 148 thyroid cases processed by Ultrafast Papanicolaou stain
      (UFP), including 43 papillary carcinomas, 38 cellular follicular lesions, and 67
      cases of nodular hyperplasia. We observed clear nuclei in all of the cases of UFP
      processed FNA and intraoperative smears of papillary carcinoma but not of other
      thyroid lesions. The clear nuclei are most evident in tumor cells with direct
      contact to the glass slide and are not seen in tumor cells soaked in cystic
      fluid. UFP is a valuable way to detect Orphan Annie-eyed clear nuclei of
      papillary thyroid carcinoma early in the diagnostic evaluation, either at
      immediate on-site evaluation of FNA or at intraoperative consultation and before
      the availability of permanent sections.

PMID- 9195570
TI  - Cytokeratin subtyping in chordomas and the fetal notochord: an
      immunohistochemical analysis of aberrant expression.
AB  - Chordoma is a well-known bone tumor that shows epithelioid features and in which
      the expression of cytokeratins (CKs) has been reported to appear very frequently.
      Numerous immunohistochemical analyses of CK expression have been conducted using
      such monoclonal antibodies as CAM5.2, which react with CK8, CK18, and CK19, and
      AE1/AE3, which react with CKs 1-8, 10, 14-16 and 19 in chordoma. No detailed
      analysis, however, of the expression of each component of CK has yet been
      conducted in chordoma; thus, the subsets of CK expressed there have yet to be
      clarified. With the use of immunohistochemical techniques with a panel of
      monoclonal antibodies against each subset of CK, the authors studied the
      expression of CKs in 16 specimens of classic chordoma and 14 specimens of the
      fetal notochord to clarify the subsets of CK expressed in chordoma and to
      evaluate the similarities and differences of CK expression between chordoma and
      the fetal notochord. All of the chordoma specimens showed a strong positive
      immunoreactivity for CK8 and CK19, whereas nine (56.3%) chordoma specimens showed
      a positive immunoreaction for CK18. In addition, four chordoma specimens were
      focally positive for keratin-903, which reacts with high molecular weight CKs
      such as CK1, CK5, CK10, and CK14; one specimen also showed a strong CK7
      expression. All of the notochord specimens were also positive for CK8 and CK19,
      but none showed a positive immunoreaction for keratin-903, CK7, or CK18. In
      addition, none of the chordoma or notochord specimens showed immunoreactivity for
      CK20. The expression of CK8 and CK19, observed in all of the chordoma and
      notochord specimens, was thus considered to be maintained throughout the
      neoplastic transformation, although some aberrant CK expressions (CK7, CK18, and
      keratin-903) also occurred in the chordoma specimens examined in this study.

PMID- 9195572
TI  - DNA ploidy and S-phase fraction by image and flow cytometry in breast cancer fine
      needle cytopunctures.
AB  - The aim of this study was to achieve a better definition of the respective
      indications of flow cytometry (FCM) and image cytometry (ICM) in clinical
      practice by comparing their efficiency in a series of 104 primary breast
      carcinomas that were sampled by means of fine-needle cytopuncture and analyzed by
      both methods. The comparison involved the DNA content and the estimation of S
      phase fraction (SPF). For this purpose, a manual rectangular model was used for
      ICM, and Modfit software was used for FCM. With respect to DNA ploidy, the
      concordance rate between the two methods was 87% (DNA diploid vs. DNA nondiploid)
      and 81% when subclasses of DNA ploidy were used (hypodiploid, diploid,
      hyperdiploid, tetraploid, or multiploid). True discordance was observed in 19
      cases (18%). Eleven of these discordances were the result of an underestimation
      of multiploidy by FCM. In the 91 cases evaluable by ICM, the SPF median value was
      3.5 for DNA-diploid tumors and 8 for DNA-nondiploid tumors. In the 67 cases
      evaluable by FCM, the SPF median value was 2.31 for DNA-diploid tumors and 5.25
      for DNA-nondiploid tumors. The concordance between ICM and FCM in the 46 uniploid
      tumors was 0.90. Our results led us to obtain samples for the two techniques
      systematically, to perform FCM routinely because it is more rapid and adequate in
      a large number of cases, to confirm by ICM any DNA-diploid or DNA near-diploid
      peak revealed by FCM, and to use ICM when FCM is inadequate, i.e., in case of low
      cellularity (fewer than 5000 cells for analysis of the cell cycle), suspected
      tetraploidy, samples not exclusively composed of malignant cells, the
      identification of several morphologically different malignant populations, or
      populations with large coefficients of variation and high background.

PMID- 9195573
TI  - Evaluation of PAPNET testing as an ancillary tool to clarify the status of the
      "atypical" cervical smear.
AB  - To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern,
      NY) in clarifying the status of cervical smears showing borderline abnormalities,
      we analyzed the results of five cytotechnologists who reclassified 200 "atypical"
      smears by evaluating PAPNET images only. The interobserver agreement
      (reliability) of the PAPNET reviewers was computed, and their readings were
      compared with three standards: the consensus diagnosis of five pathologists who
      used light microscopy, the detection of cancer-associated human papillomavirus
      DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens
      obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of
      cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous
      interobserver agreement was achieved in only 24 (13%) cases. Four of the five
      PAPNET reviewers agreed moderately well with the results of the pathology
      reference panel. In four of the five PAPNET reviews, classification of cases as
      abnormal was strongly correlated with the detection of cancer-associated types of
      human papillomavirus. Consensus PAPNET results of abnormal were predictive of
      abnormal histologic findings at follow-up. Theoretically, if colposcopy had been
      performed on all of the women with equivocal or abnormal PAPNET results (based on
      the consensus of the panel), as much as 95% of biopsy-confirmed lesions could
      have been detected, but 79% of women would have been referred. Restriction of
      colposcopy referral to women with definitely abnormal PAPNET readings would have
      reduced referrals to 31%, but the sensitivity of the triage would have dropped to
      51% of biopsy-confirmed lesions.

PMID- 9195574
TI  - Laminin and cathepsin B as prognostic factors in stage I non-small cell lung
      cancer: are they useful?
AB  - Laminin, a glycoprotein component of basement membrane, and cathepsin B, a
      lysosome-derived proteinase, are thought to play a role in the complex process of
      tumor invasion and metastasis. This study evaluates the possible prognostic
      significance of laminin degradation and cathepsin B expression in Stage I (T1NO,
      T2NO) human non-small cell lung cancer. Archival, formalin-fixed, paraffin
      embedded lung tissue from patients with documented Stage I non-small cell cancer
      was studied in a series of 31 patients (14 men, 17 women; ages 40-82 yr; mean
      age, 67 yr) by using polyclonal antibodies against laminin and cathepsin B. The
      immunoexpression of laminin was assessed with respect to a continuous versus
      discontinuous pattern, whereas that of cathepsin B was semiquantitated according
      to a four-tiered grading scale: 0, 0% positive cells; 1, 1 to 9%; 2, 10 to 49%;
      and 3, more than 50% positive cells. Cox proportional hazards models and Kaplan
      Meler survival analysis were used to evaluate the association of possible risk
      factors, including laminin and cathepsin B, with survival. Univariate analysis
      looking at possible associations of survival with age, sex, histologic type,
      degree of tumor differentiation, and tumoral stage (T1NO, T2NO) did not show
      significant association. Likewise, degradation of laminin and immunoexpression of
      cathepsin B did not show significant association with survival. Although previous
      studies suggested improved survival with increased laminin expression and
      decreased survival with high expression of cathepsin B, the results applying to
      intrastage (Stage I) non-small cell cancer suggest that the expression of laminin
      and cathepsin B has little prognostic significance.

PMID- 9195575
TI  - p53-independent expression of p21waf1/cip1 in preinvasive and invasive squamous
      neoplasms of the uterine cervix.
AB  - Although mutations of the p53 gene are the most common genetic alteration in
      human tumors, they are relatively rare in cervical carcinomas, possibly because
      human papillomaviruses of the oncogenic type encode for an oncoprotein that leads
      to the ubiquitin-mediated destruction of p53. An important mediator of p53
      induced cell-cycle arrest is p21waf1/cip1, and although several studies evaluated
      invasive and preinvasive cervical lesions for p53 expression, none has studied
      expression of this important downstream effector. We examined normal cervical
      squamous epithelium, squamous cell carcinomas, and a range of preinvasive
      cervical lesions for expression of p53, p21waf1/cip1, and the proliferation
      associated antigen, Ki-67, by immunohistochemical analysis. p53 expression was
      absent in normal squamous epithelium and all dysplasias regardless of severity,
      consistent with the presence of predominantly wild-type p53. Invasive carcinomas
      were mostly negative but contained occasional small nests of cells immunoreactive
      for p53. p21waf1/cip1, on the other hand, was expressed in all normal squamous
      epithelium and all preinvasive and invasive lesions. In normal squamous
      epithelium, the basal and immediate parabasal layers were negative, with the
      early differentiating layers positive. Expression was increased in dysplasias
      compared with normal squamous epithelium, both in number of immunoreactive nuclei
      and intensity of staining. The highest expression was seen in high-grade
      dysplasias and invasive carcinomas. Ki-67 expression also increased with
      increasing severity of the lesion, but p21waf1/cip1 and Ki-67 seemed to be
      expressed in different cells, a fact that was confirmed by double
      immunohistochemical staining for these two proteins on the same sections. This
      paradoxical increase in p21waf1/cip1 expression and mutually exclusive expression
      might be related to the role of p21waf1/cip1 in differentiation.

PMID- 9195576
TI  - Simultaneous double immunoenzymatic labeling: a new procedure for the
      histopathologic routine.
AB  - We developed a new procedure for simultaneous immunohistoenzymatic double
      labeling that uses two mouse monoclonal antibodies of different isotypes or two
      antibodies from different species. The technique is a combination of the alkaline
      phosphatase-antialkaline phosphatase, avidin-biotin, and digoxigenin methods and
      uses horseradish peroxidase and alkaline-phosphatase detection systems. This
      standardized procedure can be carried out easily in the routine of a pathology
      laboratory and performed in parallel with single-antigen immunostaining, without
      the need for extra material or additional time for the laboratory technicians.
      This method can be applied to the detection of antigens localized in distinct
      cells or subcellular compartments and to the covisualization of different
      components from the same subcellular compartment.

PMID- 9195577
TI  - Metaplastic carcinoma of the breast with melanocytic differentiation.
AB  - We report the clinical and pathologic findings of a metaplastic carcinoma of the
      breast that exhibited melanocytic differentiation. The tumor possessed both in
      situ and invasive components. Lower grade regions of the infiltrating carcinoma
      had features of tubular, mucinous, and matrix-producing carcinomas. In the higher
      grade areas, conventional poorly differentiated ductal carcinoma merged with an
      anaplastic neoplasm that looked like malignant melanoma. The nonpigmented cells
      stained for keratin but lacked HMB-45 and S-100 proteins, whereas the cells
      containing melanin showed the opposite characteristics. Electron microscopic
      examination disclosed melanosomes in the neoplastic cells. We believe that these
      observations convincingly establish both the origin of the tumor from the mammary
      epithelium and the synthesis of melanin by the tumor cells. We propose the
      diagnosis of metaplastic carcinoma with melanocytic differentiation for this
      neoplasm and suggest that the phenomenon of melanocytic metaplasia might underlie
      the formation of primary melanomas of the breast.

PMID- 9195578
TI  - Gliomatosis peritonei with malignant transformation.
AB  - A 13-year-old girl underwent a right salpingo-o-ophorectomy and partial
      omentectomy for an ovarian tumor that on microscopic examination was a grade 1
      immature teratoma. Mature glial implants were found in the omentum (Stage III).
      No additional treatment was given. Ten months later, grade 0 and grade 1
      peritoneal glial implants were found on laparotomy. Chemotherapy with four cycles
      of vincristine/cisplatin/etoposide/bleomycin was administered. A second
      laparotomy 4 months later showed persistence of grade 0 and grade 1 peritoneal
      glial implants. The patient was well for the next 7 years, after which time she
      presented with a pelvic mass that on microscopic examination was a malignant
      neuroectodermal tumor resembling a glioblastoma multiforme. The tumor did not
      respond to debulking and chemotherapy, and the patient died 6 months later, 8
      years after her initial presentation. This case represents the second report of
      malignant transformation of peritoneal glial implants.

PMID- 9195579
TI  - Gestational psittacosis: case report and literature review.
AB  - In Europe, Chlamydia psittaci is a relatively common cause of abortion in sheep
      and other mammals. Psittacosis in humans is typically described as a mild-to
      moderate flu-like illness. If psittacosis is acquired during pregnancy, it can
      present as a severe, progressive, febrile illness, with headache, disseminated
      intravascular coagulation, abnormal liver enzyme studies, and impaired renal
      function. Only cases with significant fetomaternal morbidity and mortality have
      been reported. Recovery from this disease follows termination of pregnancy and
      appropriate antibiotic therapy. Direct exposure of gravid humans to infected
      products of conception is the most commonly reported mode of transmission.
      Diagnosis is suggested by the placental histopathologic findings, which consist
      of an intense, acute intervillositis, perivillous fibrin deposition with villous
      necrosis, and large irregular basophilic intracytoplasmic inclusions within the
      syncytiotrophoblast. Commercially available genus-specific monoclonal
      antichlamydial antibody is available for the rapid confirmation of the diagnosis.
      In the United States, only two cases of gestational psittacosis have been
      previously reported. In contrast to the experience in Europe, both cases were
      associated with psittacine birds. This is the first reported instance of ovine
      related gestational psittacosis documented in the United States. Gravid patients
      should be warned to avoid contact with sheep and their products, particularly
      during the spring lambing period.

PMID- 9195580
TI  - Rhabdomyoma of the tunica vaginalis of the testis: a histologic,
      immunohistochemical, and ultrastructural study.
AB  - A case of an unusual tumor of skeletal muscle origin is described. The tumor was
      located in the tunica vaginalis of the testis in a 19-year-old man. Histologic
      examination showed a proliferation of elongated or round cells, with clearly
      discernible cross striations, surrounded by abundant mature connective tissue,
      consistent with genital rhabdomyoma. Immunohistochemical and electron microscopic
      features supported this diagnosis. Rhabdomyoma must be considered in the
      differential diagnosis of paratesticular tumors.

PMID- 9195581
TI  - Histologic variants of adenocarcinoma and other carcinomas of prostate:
      pathologic criteria and clinical significance.
AB  - Most cases of carcinoma involving the prostate gland show characteristic acinar
      histologic features. The term variant is used to describe a distinctly different
      histomorphologic phenotype of a certain type of neoplasm. The recognition of
      histologic variants of prostate carcinoma is important because some types are
      associated with a different clinical outcome and might have a different
      therapeutic approach, and because awareness of the unusual pattern might be
      critical in avoiding diagnostic misinterpretations. In this article, we review
      the subject of histologic variants of prostatic adenocarcinoma with a focus on
      histologic criteria and clinical significance. We discuss small cell carcinoma,
      ductal (endometroid) carcinoma, sarcomatoid carcinoma, signet ring cell
      carcinoma, mucinous carcinoma, lymphoepithelioma-like carcinoma, adenosquamous
      carcinoma of the prostate, squamous carcinoma, adenoid cystic carcinoma, and
      transitional cell carcinoma involving the prostate.

PMID- 9195582
TI  - Telepathologic review: utility, diagnostic accuracy, and interobserver
      variability on a difficult case consultation service.
AB  - The diagnostic accuracy of telepathologic analysis has not been compared to that
      of conventional light microscopic review on a difficult case consultation
      service. The anatomic pathology consultation files of the University of Iowa were
      retrospectively examined, and 105 difficult cases from a variety of organs were
      chosen for real-time telepathologic and light microscopic review. The
      telepathologic and light microscopic crude agreement of five pathologists were
      compared, with use of the original consultation diagnosis as the "gold standard."
      Cases were scored as correct, partially correct, or incorrect. After making a
      video diagnosis, the pathologists reported whether they wanted to review the case
      with use of a light microscope. The pathologists performed significantly better
      with the light microscope, even after excluding cases in areas of inexpertise (P
      = .005). The mean percentage of cases that the pathologists wanted to review with
      the light microscope was 64%, and the major reason for review was diagnostic
      uncertainty. Cases incorrectly diagnosed with use of the video monitor were
      almost always requested for review. We conclude that, on a difficult case
      consultation service, pathologists perform significantly better with use of light
      microscopic than with telepathologic analysis; rarely make an incorrect diagnosis
      and do not request that case for light microscopic review; and exhibit high
      telepathologic diagnostic accuracy in areas of expertise.

PMID- 9195583
TI  - Fine-needle aspiration cytology of the breast: a preliminary report on
      telepathology through Internet multimedia electronic mail.
AB  - Telepathology is a field of telemedicine that enables the exchange of histologic
      and cytologic images for consultations among pathologists of two or more remote
      institutions, through a suitable communication channel. The Internet can connect
      several scientific and medical institutions because of the existence of a set of
      standard protocols that allow different computers to communicate; multimedia
      electronic mail is one such protocol, which allows asynchronous transmission of
      multimedia documents, i.e., including text, images, movies, and sounds. The aim
      of the present article is to test a novel approach in which Internet multimedia
      electronic mail is used as a communication medium to obtain an asynchronous
      telepathology tool for remote consultation. To assess the diagnostic validity of
      the method, 48 cases of fine-needle aspiration cytology of breast lesions were
      sent from Udine to Trento, Italy. Comparisons between local and remote diagnoses,
      and cytologic diagnoses versus subsequent histologic reports demonstrated that
      Internet multimedia electronic mail is suitable for remote consultation. Internet
      multimedia electronic mail thus presents an additional diagnostic tool that is
      easy to use, available on a wide range of computers, and inexpensive, because its
      cost is independent of distance.

PMID- 9195584
TI  - Inhibitory avoidance and appetitive learning in aged normal mice: comparison with
      transgenic mice having elevated plasma growth hormone levels.
AB  - Groups of 25-month-old ("old") B6C3 hybrid male mice, 6-month-old ("young")
      normal males, and their age-matched transgenic (TG) siblings overexpressing the
      bovine growth hormone gene were given an inhibitory avoidance training trial
      (0.20-mA electric shock, 1.0-s duration). The old B6C3 hybrids and the young TG
      mice displayed poorer retention (shorter latencies to enter the shock
      compartment) 24 h and 42 days after training than did the young normal mice. In a
      subsequent multiple-trial acquisition test, young TG and old normal mice required
      more trials to reach the criterion of complete inhibition of step-through
      responding for 300 s than did young normal mice. Young normal and young TG mice
      did not differ in trials to extinction, but TG mice met the extinction criterion
      sooner than did old normal mice, suggesting poorer longterm retention. In tests
      of T-maze appetitive learning, young normal, old normal, and young TG mice did
      not differ in acquisition or 24-h retention. Contrary to expectation, TG mice
      acquired T-maze reversal learning in fewer trials than did young normal or old
      normal mice. The TG and young normal mice did not differ in retention when
      retested 44 days after initial training, but old normal mice showed poorer
      retention than did the young normals. Results of locomotor activity and shock
      response tests suggested that learning impairments were not due to differences in
      locomotor activity or shock response thresholds in these animals. Tests in an
      elevated plus maze indicated that young TG mice were less anxious in a novel
      environment than their normal siblings, which may contribute to their impaired
      inhibitory avoidance learning. These findings suggest that 6-month-old TG mice
      overexpressing the bovine growth hormone gene display alterations in inhibitory
      avoidance (but not appetitive) learning similar to those occurring in 25-month
      old normal mice. The neurobiological mechanisms mediating inhibitory avoidance
      and T-maze appetitive learning in these animals may be largely dissociated.

PMID- 9195585
TI  - Induction of multiple synapses by experience in the visual cortex of adult rats.
AB  - This study examined experience effects upon the formation of multiple synaptic
      contacts among individual dendritic and axonal elements. Axonal boutons and
      dendritic spines forming contacts with more than one process were assessed within
      layer IV of the visual cortex in adult rats following 60 days of housing in
      standard laboratory cages (IC) or in complex environments (EC). Multiple synaptic
      boutons (MSBs) that formed synaptic contacts with both a dendritic spine and a
      dendritic shaft were found to be markedly increased in number per neuron in EC
      rats in comparison to those in IC rats. In contrast, single-synaptic contacts
      were not increased, indicating that the formation of new single-synaptic boutons
      is, at most, merely sufficient to replace boutons that may have been recruited
      into the population of MSBs. This apparent tendency to reutilize presynaptic
      processes may indicate a constraint upon the formation of neural circuitry and a
      fundamental form of plastic synaptic change.

PMID- 9195586
TI  - Combined lesions of perirhinal and entorhinal cortex impair rats' performance in
      two versions of the spatially guided radial-arm maze.
AB  - The present study examined the effects of combined lesions of the entorhinal and
      perirhinal cortex (PRER) on performance of two versions of the spatially guided
      eigh-tarm radial maze. In the first version, all arms were baited and in each
      session the rats were allowed to explore the maze freely until they retrieved all
      of the reinforcers. PRER subjects were profoundly impaired in performance of this
      task, making fewer correct choices and more total errors than control subjects.
      In the second task, a delayed nonmatching to sample version of the radial-arm
      maze, each daily session was separated into two phases. In the first, predelay
      phase, four arms were open and the remaining four arms were blocked with clear
      Plexiglas barriers; subjects were permitted to visit each of the four arms and
      retrieve the reinforcers. In the second, postdelay phase, the subject was placed
      on the maze with free access to all eight of the arms, but only those arms that
      were blocked in the predelay phase contained reinforcers. Delays of either 10 min
      or 30 s separated the pre- and postdelay phases. PRER subjects were significantly
      impaired in their performance of this task at both delays, making fewer correct
      choices and more errors than controls; the magnitude of this deficit was not
      dependent on length of delay. These data suggest that, along with the hippocampal
      formation, the entorhinal and perirhinal cortices actively participate in the
      acquisition and performance of appetitively motivated spatial memory tasks.

PMID- 9195587
TI  - Strategies used by hippocampal- and caudate-putamen-lesioned rats in a learning
      task.
AB  - In rats, hippocampal lesions result in impairment of spatial navigation, although
      other learning abilities remain unaltered. When learning a left/right
      discrimination task, rats can use a spatial strategy (with external maze
      landmarks-Situation 1) or are forced to use an egocentric strategy (without
      external or internal maze cues-Situation 2). Little is known about the
      extrahippocampal systems involved in the utilization of egocentric strategy. It
      is suggested that striatum could play an important role in the learning abilities
      that are spared after hippocampal lesion. The aim of our study was to investigate
      which strategy is used by rats bearing hippocampal or caudate-putamen lesions in
      the acquisition of a left/right discrimination task in an elevated T-maze in both
      Situations 1 and 2. We also investigated the effect of each lesion on the
      reversal of discrimination in both situations. Acquisition was not altered in any
      of the situations; however, a transfer test showed that hippocampal-lesioned rats
      used a different strategy (egocentric) from control animals (spatial) in
      Situation 1. In addition, reversal of the discrimination was impaired in
      Situation 2. Caudate-putamen lesion produced a transient effect on reversal of
      discrimination only in the egocentric task (Situation 2), but did not impair
      acquisition of the task in either situation, thus suggesting that the animals
      were able to use either strategy.

PMID- 9195588
TI  - Posttraining injections of MK-801 produce a time-dependent impairment of memory
      in two water maze tasks.
AB  - The role of glutamatergic N-methyl-D-aspartate (NMDA) receptors in memory storage
      processes was examined using systemic posttraining injections of MK-801. Male
      Long-Evans rats received an eight-trial (30-s ITI) training session on a spatial
      or cued water maze task. In the spatial task, a submerged escape platform was
      located in the same quadrant of the maze on all trials. In the cued task, a
      visible escape platform was located in a different quadrant of the maze on each
      trial. Following Trial 8 in both tasks, the rats received a posttraining
      intraperitoneal injection of the NMDA receptor antagonist MK-801 (0.025, 0.05,
      0.1, or 0.2 mg/kg) or saline. On a retention test session 24 h later, latency to
      mount the escape platform was used as a measure of memory. In both tasks, the
      retention test escape latencies of animals given MK-801 (0.05 and 0.1 mg/kg) were
      significantly higher than those of saline-injected controls, indicating a drug
      induced impairment of memory. Injections of MK-801 (0.05 mg/kg) did not affect
      retention when administered 2 h posttraining in either task, indicating that the
      effects of MK-801 on retention are not due to an influence on non-mnemonic
      factors. Control experiments indicated that the memory impairing effects of MK
      801 were due to an influence on memory for the type of discrimination training
      given (i.e., spatial or cued) and not due to an influence on a mnemonic strategy
      common to both tasks. The findings indicate a time-dependent role for NMDA
      receptor function in memory storage processes.

PMID- 9195589
TI  - Posttraining intraamygdala infusions of oxotremorine and propranolol modulate
      storage of memory for reductions in reward magnitude.
AB  - These experiments examined the effects of posttraining intraamygdala
      administration of the muscarinic agonist, oxotremorine, and the beta
      noradrenergic antagonist, propranolol, on memory for reduction in reward
      magnitude. Male Sprague-Dawley rats (175-200 g) implanted with bilateral
      intraamygdala cannulae were food deprived (maintained at 80% of body weight) and
      trained to run a straight alley (six trials/day) for either ten 45-mg food
      pellets (high reward) or one 45-mg food pellet (low reward) for 10 days. In
      Experiment One, the animals in the high-reward group were than shifted to a one
      pellet reward and immediately given intraamygdala infusions (0.5 microliter/side)
      of either oxotremorine (10 ng) or phosphate buffer. Shifted training continued
      for 4 more days and no further injections were given. Shifted animals given the
      buffer solution displayed an increase in runway latencies but returned to
      preshift latencies by the fifth day of shifted training. In contrast, animals
      given oxotremorine exhibited increased latencies through the fifth day. In
      Experiment Two, rats were trained as in Experiment. One but immediately following
      the shift received intraamygdala infusions of oxotremorine (10 ng), propranolol
      (0.3 microgram), both, or phosphate buffer. Shifted vehicle-injected rats
      returned to preshift performance by the fifth day of shifted training. Shifted
      propranolol rats returned to preshift latencies by the third day of shifted
      training. In contrast, the shifted oxotremorine and the shifted
      oxotremorine/propranolol rats displayed longer latencies than unshifted controls
      through 5 days of shifted training. The findings indicate that the muscarinic
      cholinergic and beta-noradrenergic systems within the amygdala interact in
      regulating memory and support the view that noradrenergic influences are mediated
      through cholinergic activation.

PMID- 9195590
TI  - Retrieval of overtrained place navigation during occlusion of one eye and ipsi-
      or contralateral blockade of relevant brain centers in rats.
AB  - Place navigation engrams acquired with intact brain can be retrieved with either
      eye and are stored in both hemispheres. The retrieval circuitry was examined by
      testing an overtrained rat under lidocaine inactivation of the hippocampus,
      visual cortex, and superior colliculus. Thirty-three hooded rats with implanted
      cannulae aimed at the above structures were trained to find a target in the
      southwest quadrant of the pool. Retrieval was tested during occlusion of one eye
      alone or combined with ipsi- or contralateral blockade (1 microliter 4%
      lidocaine) of hippocampus, hippocampus and visual cortex, or hippocampus, visual
      cortex, and superior colliculus. The intact brain escape latencies (9.8 s) were
      only slightly prolonged by occlusion of one eye (to 12.6 s). Blockade of centers
      ipsi- or contralateral to the occluded eye increased escape latencies to 12.7 or
      15.2 s for hippocampus, to 16.8 or 16.9 s for hippocampus and visual cortex, and
      to 23.6 or 17.4 s for hippocampus, visual cortex, and superior colliculus,
      respectively. Significant asymmetry appearing in the last case indicates that the
      superior colliculus plays an important role in mediation of the crossed visual
      input supporting place navigation. Residual goal-finding capability in rats with
      blockade of centers ipsilateral to the occluded eye is probably due to uncrossed
      visual projections to the intact hemisphere.

PMID- 9195591
TI  - Effects of habenular lesions upon two-way active avoidance conditioning in rats.
AB  - To evaluate if habenular nuclei lesions improve, impair, or have no effects on
      two-way active avoidance acquisition and/or retention, rats in a Lesion group
      were subjected to bilateral electrolytical lesions of this complex, while control
      rats were sham-operated (Sham group). Once recovered from the stereotaxic
      procedures, rats were submitted to 5 training sessions (10 trials each, one
      session per day) of two-way active avoidance conditioning. Ten days after the
      last training session, another session was administered in order to test the long
      term retention of the task. Results indicated that habenular lesions did not
      affect the overall performance of the rats during either the acquisition sessions
      or the retention session of two-way active avoidance. We suggest that habenular
      lesions can affect the acquisition of several learning tasks, probably through
      their role in modulating stress responses and/or arousal states. The nature of
      these effects (whether facilitative, detrimental, or neutral) might depend on the
      interaction between several factors such as the kind of task, the specific
      conditioning procedures (which may generate different stress levels), and the
      specific area destroyed by the lesion.

PMID- 9195592
TI  - Intraseptal infusions of muscimol impair spontaneous alternation performance:
      infusions of glucose into the hippocampus, but not the medial septum, reverse the
      deficit.
AB  - As observed with intraseptal injections of opioid receptor agonists, direct
      infusions of GABAergic receptor agonists into the medial septum impair
      performance on several tasks that involve spatial or working memory processes in
      rats. Because the effects of opioid-induced impairments can be reliably reversed
      by concomitant intraseptal infusions of glucose, the experiments reported here
      determined whether impairments produced by GABAergic agonists would similarly be
      reversed by glucose. The findings of Experiment 1 showed, in male Sprague-Dawley
      rats, that intraseptal infusions of the GABA agonist muscimol (1 or 3 nmol/0.5
      microliter) impaired spontaneous alternation performance. The results of
      Experiment 2 indicated that intraseptal infusions of glucose (8, 17, or 33 nmol)
      or glutamate (15 or 30 nmol) did not attenuate the muscimol-induced deficit on
      spontaneous alternation performance, whereas infusions of the GABAergic
      antagonist bicuculline methiodide (0.1 nmol) did. However, the findings of
      Experiment 3 indicated that glucose injections (50 nmol/0.5 microliter) into the
      hippocampus did reverse the impairing effect of the intraseptal muscimol
      infusions. Combined, these findings suggest that the neurochemical regulation of
      learning and memory may involve hierarchical interactions between particular
      neurotransmitter and neuroanatomical systems. Specifically, medial septal
      GABAergic effects on spontaneous alternation prevail over those of glucose or
      glutamate in the medial septum, but are overridden by the effects of glucose in
      the hippocampus.

PMID- 9195593
TI  - Comparison of the behavioral and morphological effects of colchicine- or neutral
      fluid-induced destruction of granule cells in the dentate gyrus of the rat.
AB  - Virtually complete destruction of dentate gyrus granule cells by colchicine
      injections produced a persistent incapacity to solve spatial problems in rats. A
      topographically more selective but only locally complete destruction of granule
      cells using injections of neutral fluid (NFL) impaired acquisition during the
      initial stages of Morris water maze testing, thus indicating that limited
      degeneration of granule cells may weakly but significantly alter spatial learning
      capabilities. A subamnestic dose (0.08 mg/kg ip) of the NMDA antagonist MK-801
      worsened radial maze performance only in NFL-treated rats, suggesting that there
      may be a synergistic interaction between NMDA blockade and limited granule cell
      degeneration.

PMID- 9195594
TI  - The contribution of stressor intensity, duration, and context to the stress
      induced facilitation of associative learning.
AB  - Exposure to an acute stressor of restraint and intermittent tailshock facilitates
      acquisition of the classically conditioned eye-blink response 24 h after stressor
      cessation. The contribution of stressor intensity, duration, and context was
      determined. Male rats exposed to 90 or 30 1-mA tailshocks exhibited sensitization
      to an auditory cue of 86 dB and facilitated acquisition of the conditioned
      response, whereas rats exposed to 90 0.5-mA tailshocks or restraint alone only
      exhibited sensitization. Rats exposed to the 5 1.0-mA tailshocks (and 5 min of
      restraint) exhibited neither sensitization nor facilitated acquisition. Rats
      stressed in the same context 48 and 96 h earlier exhibited sensitization and
      facilitated acquisition relative to those stressed in a different context.
      Neither stressed group exposed to unpaired stimuli responded to the CS, and thus
      there was no pseudodconditioning. Together, these results dissociate the stress
      induced sensitization from the facilitated learning. They also indicate that the
      facilitated learning is particularly sensitive to stressor intensity and
      contextual cues.

PMID- 9195595
TI  - Intrahippocampal injections of exogenous beta-amyloid induce postdelay errors in
      an eight-arm radial maze.
AB  - Alzheimer's disease is characterized by the progressive loss of short-term memory
      and the accumulation of large amyloid plaques, the primary core of which is the
      beta-amyloid 1-40 (beta A4) peptide. It has been suggested that beta A4 plays a
      causative role in the memory degeneration seen in Alzheimer's patients. The
      current study was designed to test the effects of bilateral intrahippocampal
      injections of beta A4 on performance in a radial arm maze foraging task with a
      delay imposed following the fourth choice. Eight Sprague-Dawley rats were
      injected with either beta A4 (10(-3) M) or vehicle (HPLC buffer) immediately
      prior to testing in the maze. Although beta A4 did not impair performance on the
      predelay choices, it did significantly increase errors immediately postdelay.
      These results suggest that contrary to previous findings, beta A4 does have acute
      effects when challenged with a short-term memory load and may play a significant
      role in some memory deficits seen in Alzheimer's disease.

PMID- 9195596
TI  - Behavioural pharmacology of glutamate receptors in the basal ganglia.
AB  - Glutamate receptors play a major role in the transmitter balance within the basal
      ganglia (BG). N-methyl-D-aspartate (NMDA) receptor stimulation within the
      striatum acts behaviourally depressant while intrastriatal as well as systemic
      administration of NMDA receptor-antagonists have rather stimulatory effects
      despite the different profiles of non-competitive-, competitive NMDA receptor-
      and glycine site-antagonists. In animal models of Parkinson's disease all these
      NMDA receptor antagonists counteract parkinsonian symptoms or act synergistically
      with L-3,4-dihydroxyphenylalanine (L-DOPA). The strong locomotion-inducing effect
      of the non-competitive NMDA receptor antagonists is partly, but not fully,
      mediated by a dopamine (DA) release in the nucleus accumbens. Manipulations at
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors produce
      poor behavioural effects. These, however, are different or even opposed to NMDA
      receptor mediated effects. Local infusions of AMPA receptor-antagonists into the
      BG output nuclei have an anti-parkinsonian effect but systemic injections are
      ineffective. These drugs even counteract the anti-parkinsonian effect of DA
      agonists and of non-competitive NMDA receptor antagonists as well as the DA
      releasing effects of the latter drugs. Only few data on the role of metabotropic
      receptors exist but the different receptor subtypes with different regional
      distribution represent a promising target for pharmacological interventions.

PMID- 9195597
TI  - Dopamine/glutamate interactions in Parkinson's disease.
AB  - In Parkinson's disease, the tonic inhibition by basal ganglia output structures
      may be exacerbated by the action of the subthalamic nucleus. As expected, the
      reduction of excitatory impact from this structure has been shown to reduce
      akinesia in monkeys with experimental parkinsonism. The findings of receptor
      binding studies supporting an increased neuronal activity of efferents of the
      subthalamic nucleus in patients with Parkinson's disease, suggest that
      subthalamic nucleotomy or pallidotomy may be effective lesions in the
      neurosurgical treatment of Parkinson's disease. Systemic administration of
      glutamate antagonists has been shown to have anti-akinetic effects in animal
      models of Parkinson's disease. Other observations in monkeys indicate that
      excitatory amino acids such as glutamate are involved in the pathophysiological
      cascade of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neuronal
      cell death. The neuroprotective effects of competitive and non-competitive NMDA
      (N-methyl-D-aspartate) receptor antagonists against MPTP toxicity support the
      hypothesis that NMDA receptor-mediated events are involved in the neurotoxicity
      of MPTP. Glutamate antagonists may therefore be able to retard the progression
      and to improve the symptomatology of Parkinson's disease. Several compounds with
      anti-parkinsonian effects such as amantadine, memantine, budipine and
      orphenadrine have been shown to be non-competitive NMDA receptor antagonists and
      are candidates for clinical trials on the neuroprotective efficacy of NMDA
      receptor antagonism. Furthermore, glutamate antagonists are useful in the
      treatment of the akinetic parkinsonian crisis, a severe form of clinical
      deterioration in patients with Parkinson's disease.

PMID- 9195598
TI  - Species differences in the role of excitatory amino acids in experimental
      parkinsonism.
AB  - The present review discusses species differences in relation to the effects
      produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP);
      in particular, it focuses on recent evidence regarding the role of excitatory
      amino acids in experimental parkinsonism. The main aim of the review is to
      provide a phylogenetic perspective which may serve as a useful tool to study
      Parkinson's disease in rodents. Excitotoxicity might represent the final common
      pathway on which the actions of different neurotoxins, selectively directed
      towards nigrostriatal dompaminergic neurons, converge. This is clearly
      demonstrated in methamphetamine- and 6-dihydroxy-dopamine-induced parkinsonism.
      The role of excitotoxicity in the mechanism of action of MPTP is less clear.
      Although there are several species differences for MPTP it is possible to obtain
      in mice the same effects induced in MPTP-treated primates by combining
      acetaldehyde or diethyldithiocarbamate with MPTP administration. When mice are
      administered these combined treatments, the onset of experimental parkinsonism
      can be prevented using the same pharmacological agents (i.e. glutamate N-methyl-D
      aspartate antagonists) that are effective in primates.

PMID- 9195599
TI  - Sensitization of the striatal dopaminergic system induced by chronic
      administration of a glutamate antagonist in the rat.
AB  - The aim of the present study was to assess in the rat the pharmacological,
      biochemical and molecular (including in situ hybridization) consequences in the
      striatum of a prolonged (50 days) treatment with dizocilpine maleate (MK-801), an
      N-methyl-D-aspartate (NMDA) antagonist. We observed a sensitization-like effect
      characterized by a behavioural hyperresponsiveness to an acute injection of
      haloperidol (0.25 mg/kg), a dopaminergic antagonist. In rats chronically treated
      with MK-801, this hyperresponsiveness was associated with an increased D2
      receptor (D2R) density in the striatum. At the transcriptional level, the D2R
      mRNA was also enhanced in the striatum. Quantitative in situ hybridization
      studies revealed that the number of neurons expressing the D2R mRNA was
      significantly enhanced in treated rats, whereas the mean amount of message per
      cell was unchanged. These changes could represent the neurobiological substrate
      of the observed sensitization. These results suggest that the D2R gene is under
      glutamate control via NMDA receptor in striatal neurons.

PMID- 9195600
TI  - Differential effects of bilateral dopamine depletion in neonatal and adult rats.
AB  - Both Lesch-Nyhan syndrome and Parkinson's disease are associated with decreased
      brain dopamine, yet each disorder is characterized by a different set of motor
      symptoms. Lesch-Nyhan syndrome is manifested in early childhood, while
      parkinsonism usually does not appear until adulthood, suggesting that age at the
      time of dopamine loss is one determinant of the effects of neurotransmitter
      deficiency. Support for this view is found in studies of animals given dopamine
      depleting lesions at different ages and then tested in adulthood. Animals
      lesioned as neonates show a supersensitivity to dopamine agonists, especially D1
      dopamine receptor agonists, and to MK-801, an NMDA receptor antagonist. In
      addition, neonatally treated animals show a 'priming' effect following repeated
      exposure to D1-dopamine agonists. Animals depleted of dopamine as adults are more
      supersensitive to agonists acting on the D2-dopamine receptor, and do not
      evidence priming to dopamine agonists or an enhanced response to MK-801. These
      differential pharmacological profiles suggest that the changes in
      neurotransmitter systems following dopamine depletion are, at least in part,
      determined by age at the time of the lesion.

PMID- 9195601
TI  - Stimulation of basal and L-DOPA-induced motor activity by glutamate antagonists
      in animal models of Parkinson's disease.
AB  - In parkinsonism, glutamate pathways within the basal ganglia become overactive,
      leading to the suggestion that glutamate antagonists might possess
      antiparkinsonian qualities. This report examines the motor properties of
      antagonists of NMDA and AMPA-type glutamate receptors, as well as some inhibitors
      of glutamate release, in animal models of idiopathic Parkinson's disease. High
      affinity NMDA open-channel blockers (e.g. MK 801, phencyclidine), are highly
      potent antagonists with inconsistent antiakinetic and strong myorelaxant
      activity. Other compounds are better tolerated and are capable of relieving
      immobility and muscular rigidity by themselves (e.g. 1-aminoadamantanes,
      polyamine site antagonists, kappa agonists, riluzole). Yet others do not restore
      movements alone (e.g. dextromethorphan, ketamine), but may interact with and
      strengthen the antiparkinsonian action of L-DOPA (e.g. competitive NMDA and AMPA
      antagonists, lamotrigine). They may do this by potentiating dopaminergic
      behaviours mediated by D1 or D2 receptors, or by some other mechanism.

PMID- 9195602
TI  - Modulation of levodopa-induced motor response complications by NMDA antagonists
      in Parkinson's disease.
AB  - The complex dopamine-glutamate interactions within the basal ganglia are
      disrupted by chronic nigrostriatal denervation and standard replacement therapy
      with levodopa. Acute N-methyl-D-aspartate (NMDA) receptor blockade is able to
      overcome the changes in dopamine D1- and D2-dependent responses and the
      progressive shortening in the duration of response induced by long-term exposure
      to levodopa in 6-hydroxydopamine-lesioned rats. Preliminary results further
      suggest that NMDA receptor blockade can counteract levodopa-induced dyskinesias
      in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned non-human primates and
      parkinsonian patients without substantially altering the motor benefit derived
      from levodopa. These results appear to be in accordance with our 2-deoxyglucose
      studies in 6-hydroxydopamine-lesioned rats showing that NMDA receptor blockade
      can attenuate many of the changes in synaptic activity induced by levodopa,
      particularly in the striatopallidal complex. Taken together, our observations
      suggest that abnormal glutamate transmission or dysregulation of NMDA receptor
      mediated mechanisms contribute to levodopa-induced motor response complications.
      Additional preclinical and clinical experiments need to be completed with well
      tolerated glutamate antagonists to determine the full potential of glutamate
      receptor blockade as a long-term strategy against levodopa-related motor response
      complications in Parkinson's disease.

PMID- 9195603
TI  - Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents-
      preclinical studies.
AB  - Aminoadamantanes such as 1-aminoadamantane (amantadine) and 1-amino-3,5
      dimethyladamantane (memantine) are N-methyl-D-aspartate (NMDA) receptor
      antagonists which show antiparkinsonian-like activity in animal models and in
      Parkinson's patients. The issue of whether NMDA antagonism plays a role in the
      symptomatological antiparkinsonian activity of amantadine and memantine is
      addressed by comparing: behaviourally effective doses, serum/brain levels, and
      their potency as NMDA receptor antagonists. In the case of memantine, blockade of
      NMDA receptors is probably the only mechanism responsible for antiparkinsonian
      activity, whereas for amantadine the situation is clearly far more complex. There
      are a number of differences between memantine and amantadine both in vitro and in
      vivo, and although NMDA receptor antagonism certainly participates in the
      antiparkinsonian activity of amantadine, other effects, some of which are
      elusive, also play a role. Moreover, it has been suggested that the
      pathomechanism of Parkinson's disease involves excitotoxic processes and that
      treatment with NMDA receptor antagonists might also slow the progression of
      neurodegeneration. If this claim is true, such an effect could be achieved with
      amantadine and memantine which show neuroprotective activity in animals at
      therapeutically relevant doses.

PMID- 9195604
TI  - Reversal of parkinsonian symptoms in primates by antagonism of excitatory amino
      acid transmission: potential mechanisms of action.
AB  - Parkinsonism is characterised by overactive glutamatergic transmission in the
      cortico-striatal and subthalamo-medial pallidal pathways. Local blockade of
      glutamatergic transmission in these pathways can alleviate parkinsonian symptoms.
      The effectiveness of the treatment, however, is often limited by the simultaneous
      appearance of unwanted side-effects. These side-effects, including ataxia and
      dissociative anaesthesia, are particularly problematic when N-methyl-D-aspartate
      (NMDA) antagonists are used. In an attempt to overcome these problems we have
      attempted to manipulate excitatory amino acid (EAA)-mediated neurotransmission
      indirectly by targeting the NMDA receptor associated modulatory sites. We review
      evidence which demonstrates that antagonists for both the NMDA associated glycine
      and polyamine sites can reverse parkinsonian symptoms when injected intra
      cerebrally in both MPTP-treated and bilateral 6-OHDA lesioned marmosets without
      eliciting unwanted side-effects. We further review preliminary data which suggest
      that ifenprodil, a polyamine site antagonist, has striking anti-parkinsonian
      actions in the marmoset. Potential mechanisms of action underlying these effects
      are discussed in terms of NMDA receptor subtypes and the neuroanatomical locus of
      action. The anti-parkinsonian efficacy of intra-striatally administered EAA
      antagonists leads us to question the view of dopamine acting in the striatum as a
      simple neuromodulator.

PMID- 9195606
TI  - Glutamatergic control over brain dopamine release in vivo and in vitro.
AB  - Substantial evidence supports an important role for the excitatory
      neurotransmitter L-glutamate as a modulator of dopamine release in the central
      nervous system. All of the established glutamate receptor subtypes identified to
      date have been implicated in the regulation of dopamine release. It appears that
      glutamate can exert both facilitatory and inhibitory control over dopamine
      release and that this may be both phasic and tonic in nature. This regulatory
      role suggests that drugs acting at glutamate receptors may be potentially useful
      therapeutic agents in neurological disorders such as parkinsonism and
      schizophrenia.

PMID- 9195605
TI  - Glutamate antagonists and Parkinson's disease: a review of clinical data.
AB  - Several lines of evidence demonstrate that glutamate antagonists can reverse
      experimental parkinsonism in animals. However, few clinical studies have been
      undertaken, principally because there is a shortage of glutamate antagonists
      which are considered safe for human use. This paper details the results of
      preliminary studies carried out on dextromethorphan, an anti-tussive agent and a
      weak open-channel blocker of the NMDA receptor; and the cerebral anti-ischaemic
      drug ifenprodil, a novel non-competitive inhibitor of the polyamine modulatory
      site on the NMDA receptor. Trials with these two compounds in small groups of
      parkinsonian volunteers have not demonstrated conclusive symptomatic improvement.
      These results do not exclude a possible role for NMDA receptor antagonists in the
      pharmacotherapy of Parkinson's disease, but rather point to the need for
      developing more potent and safe NMDA antagonists, with better pharmacodynamic and
      pharmacokinetic profiles.

PMID- 9195607
TI  - On the release of glutamate and aspartate in the basal ganglia of the rat:
      interactions with monoamines and neuropeptides.
AB  - Using highly sensitive analytical procedures, glutamate (Glu), aspartate (Asp)
      and several putative neurotransmitters and metabolites can be monitored
      simultaneously in the extracellular space of neostriatum, substantia nigra and
      cerebral cortex of the rat by in vivo microdialysis. Glu and Asp are found at sub
      micromolar concentrations in all investigated brain regions. In order to
      ascertain their neuronal origin, we have extensively studied the sensitivity of
      extracellular Glu and Asp levels to: (i) K(+)-depolarization, (ii) Na(+)-channel
      blockade, (iii) removal of extracellular Ca2+, (iv) depletion of presynaptic
      vesicles, and (v) integrity of neuronal pathways. The relevance of these criteria
      for several neurotransmitters monitored simultaneously or in parallel experiments
      has also been examined. The functional interactions among different neuronal
      pathways in the basal ganglia are studied by using selective pharmacological
      treatments, administered systemically, or locally via intracerebral injections or
      the microdialysis perfusion medium. Immunohistochemical evidence for the
      existence of Glu and/or Asp neuronal pathways in the basal ganglia of the rat is
      presented, discussing especially new findings indicating the existence of a Glu
      independent Asp system, intrinsic to the neostriatum of the rat. The clinical
      relevance of these interactions is discussed, focusing on the implications for
      the treatment of neurodegenerative disorders affecting the basal ganglia.

PMID- 9195608
TI  - Dopamine and glutamate control each other's release in the basal ganglia: a
      microdialysis study of the entopeduncular nucleus and substantia nigra.
AB  - This study utilized microdialysis in conscious rats to investigate dopaminergic
      control of excitatory amino acid release in the entopeduncular nucleus (EPN), and
      glutamatergic control of dopamine release in the substantia nigra pars reticulata
      (SNr). EPN dialysates contained both glutamate and aspartate, which were elevated
      by dopamine depletion with reserpine and 6-hydroxydopamine (6-OHDA), reduced by
      the D2/3 agonist LY 171555 and unaffected by the D1 agonist SKF 38393, in line
      with current theory. The D2/3 agonist RU 24213 was behaviourally active but
      paradoxically increased glutamate and aspartate release in EPN, possibly via
      kappa opioid receptor blockade. 6-OHDA-hemilesioned rats also showed a
      significant increase in glutamate and aspartate contralaterally, suggesting that
      nigrostriatal dopamine affects EPN neurotransmission bilaterally. In reserpine
      treated rats, basal levels of dopamine in the SNr were greatly reduced, and were
      further lowered by focal application of NMDA antagonists, suggestive of the
      removal of a high glutamatergic tone. A threshold amount of L-DOPA applied to the
      SNr elevated dopamine output about two-fold and 5-HT output about 13-fold,
      indicating L-DOPA effects the release of monoamines other than dopamine.
      Concomitant addition of the NMDA antagonists potentiated these releases
      synergistically, suggesting that this could be how they facilitate the
      antiparkinsonian action of L-DOPA.

PMID- 9195609
TI  - Dopamine/glutamate interaction as studied by combining turning behaviour and c
      Fos expression.
AB  - Dopamine (DA) and glutamate N-methyl-D-aspartate (NMDA) receptors extensively
      interact in the mediation of motor behaviours originated in basal ganglia. In
      unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, this interaction is of a
      different sign depending on whether D1 or D2 receptors are stimulated.
      Contralateral turning behaviour induced by D1 agonists is potentiated by the NMDA
      antagonist MK 801, while turning behaviour induced by D2 agonists is decreased.
      NMDA receptors not only modulate the acute turning behaviour induced by DA
      agonists but also the long-term effects induced by stimulation of DA receptors.
      MK 801, in fact, prevents the sensitization (priming) of D1-mediated turning
      behaviour induced by a single exposure to a DA agonist. Prevention of priming by
      MK 801, also appears to be different depending on whether D1 or D1/D2 receptors
      are stimulated. Studies on c-fos expression induced by DA D1 agonists in the 6
      OHDA lesioned striatum show that detection of Fos-like immunoreactivity
      correlates to the long-term but not the acute effects induced by DA receptor
      stimulation and NMDA receptor blockade.

PMID- 9195610
TI  - Modulation of dopamine neuronal activity by glutamate receptor subtypes.
AB  - In vitro and in vivo electrophysiological studies have been used to assess the
      effects of glutamate, as well as specific agonists and antagonists for
      ionotropic, N-methyl-D-aspartate (NMDA), (R,S)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) and kainate, and metabotropic subtypes of
      the glutamate receptor, on the neuronal firing activity of midbrain, substantia
      nigra zona compacta (A9) and ventral tegmental area (A10), dopamine neurons. In
      in vitro experiments, agonists for all glutamate receptor subtypes depolarize the
      membrane and increase firing rate. In in vivo experiments, iontophoretic
      application of these agonists increases the firing rate and induces burst-firing.
      Studies with subtype selective antagonists suggest that a tonic glutamate tone,
      acting via NMDA receptors, may modulate the firing activity of some dopamine
      neurons. Glutamatergic afferents from the subthalamus, pedunculopontine nucleus
      and frontal cortex can modulate the firing activity of dopamine neurons. The
      role(s) of the different glutamate receptor subtypes and pathways in mediating
      the physiological and pathological effects on dopamine systems is an area for
      further investigation.

PMID- 9195611
TI  - Synaptic plasticity and physiological interactions between dopamine and glutamate
      in the striatum.
AB  - Several electrophysiological studies have addressed the interaction between
      glutamate and dopamine within the striatum. Although the results obtained from
      these studies were often conflicting, more recently the characterization of new
      forms of synaptic plasticity in the basal ganglia provided a possible integrative
      explanation of the different electrophysiological data regarding the interaction
      between these transmitters. In this review we will try to summarize and discuss
      the available data concerning the possible impact of the functional role of D1
      and D2 receptor activation on the modulation of the glutamatergic corticostriatal
      pathway. Moreover, we will also describe the function of the striatum in the
      integration of glutamatergic and dopaminergic inputs to produce long-term changes
      of synaptic efficacy (long-term depression, long-term potentiation). Finally, we
      will consider the implication of the interaction between dopamine and glutamate
      in the regulation of energetic metabolism whose failure is responsible for
      neuronal death.

PMID- 9195612
TI  - Standard of care: so who decides?

PMID- 9195613
TI  - Laser artifacts and diagnostic biopsy.

PMID- 9195614
TI  - Residual cyst?

PMID- 9195615
TI  - Focal lymphadenopathy and intermittent fever in a 17-year-old girl.

PMID- 9195616
TI  - Mortality incidence in outpatient anesthesia for dentistry in Ontario.
AB  - Studies determining anesthesia mortality rates in dentistry have been published,
      yet a similar investigation has never been conducted in Canada. Therefore the
      objective of this study was to determine the incidence of mortality when general
      anesthesia or deep sedation was administered by qualified dentists in the
      province of Ontario. Mortality data were obtained from the years 1973 to 1995
      inclusive. The number of general anesthetics and deep sedations administered
      annually by qualified in dental offices was calculated by surveying all oral and
      maxillofacial surgeons and dental anesthetists in Ontario in 1990 and 1995. The
      results provided an estimate of 2,830,000 cases from 1973 to 1995 inclusive. Over
      this time period there were four deaths associated with cases in which either an
      oral and maxillofacial surgeon or dental anesthetist administered the general
      anesthetic or deep sedation, yielding a mortality rate of 1.4 per 1,000,000. This
      mortality incidence is similar to rates already published for outpatient
      dentistry.

PMID- 9195617
TI  - Cervicofacial actinomycosis: a diagnostic challenge.
AB  - Actinomycosis was first described as a clinical entity over 100 years ago.
      However, the fundamental characteristics of this entity have not been fully
      discussed, and major questions remain unanswered, such as the highly diversified
      pathogenicity of the phenomenon according to numerous published case reports and
      clarification of solid diagnostic criteria. Even the frequency of cervicofacial
      actinomycosis occurrence is unclear; some authors consider it to be rare and
      others to be common. We present 11 cases examined and treated in our department
      within the last 14 years along with a review of the literature. Diagnostic
      problems are emphasized, and a comprehensive overview of the entity is suggested.

PMID- 9195618
TI  - Postradiation osteonecrosis of the mandible: a long-term follow-up study.
AB  - OBJECTIVES: The objective of this study was to assess the long-term progress of
      26 patients who experienced postradiation osteonecrosis of the jaw between 1975
      and 1989. STUDY DESIGN: Of 26 patients who had been previously managed with
      hyperbaric oxygen therapy as a part of their treatment for postradiation
      osteonecrosis of the jaw, 20 were evaluated to determine their current status of
      the condition: resolved, chronic persisting (unresolved), or active progressive
      (symptomatic). RESULTS: Two of 20 patients experienced recurrences of the
      condition. In one of these patients, surgical treatment was identified as the
      stimulus of postradiation osteonecrosis. In the other patient, the recurrence
      appeared to be related to periodontal disease activity. In 60% (12 of 20) of the
      patients, the condition remained resolved, improvement in clinical staging
      occurred in 10% (2 of 20) (from symptomatic to unresolved or resolved), and 20%
      (5 of 20) of the patients continued to demonstrate chronic persisting
      postradiation osteonecrosis at the end of the long-term follow-up period.
      CONCLUSION: This study supports the contention that postradiation osteonecrosis
      can occur at any time after radiation therapy, and that patients remain at risk
      up to 231 months after treatment of the cancer and probably indefinitely after
      radiation therapy. Our findings also suggest that risk of second episodes of the
      condition after management of an initial episode is low. In addition, our follow
      up study revealed that chronic nonprogressive postradiation osteonecrosis can
      remain stable without extensive intervention including combined hyperbaric oxygen
      therapy and surgery.

PMID- 9195619
TI  - Mental nerve neuropathy as a result of hepatitis B vaccination.
AB  - We describe a 20-year-old woman who presented with polyarthralgia and sensory
      neuropathy, including mental nerve neuropathy. The symptoms were attributed to
      hepatitis B vaccination. This unusual cause of mental nerve neuropathy has not
      been previously described. However, as the use of hepatitis B vaccination is
      growing, adverse side effects, including mental nerve neuropathy, should be
      observed with an increased frequency.

PMID- 9195620
TI  - "Scalded mouth syndrome" caused by angiotensin converting enzyme inhibitors: two
      case reports.
AB  - Two cases of "scalded mouth syndrome" are presented and discussed. This condition
      is a rare side effect of angiotensin converting enzyme inhibitors. Angiotensin
      converting enzyme inhibitors are known to cause several other oral and extra-oral
      side effects. In scalded mouth syndrome, the patient's complaints concern a
      burning pain of the oral soft tissues. There are no clinical findings.

PMID- 9195621
TI  - Oral sarcoidosis with tongue involvement.
AB  - A case of oral sarcoidosis involving the tongue and buccal region is reported in
      a 56-year-old woman. Intraoral presentations of sarcoidosis are uncommon, and
      sarcoidosis of the tongue is particularly rare. In this case the tongue lesion
      was asymptomatic, and unusual clinical behavior. In this article, we review the
      clinical manifestations, diagnostic procedures, differential diagnosis and
      treatments of oral sarcoidosis.

PMID- 9195622
TI  - Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of
      Teachers of Oral Pathology.
AB  - A workshop to discuss primary oral melanomas was convened at the annual Western
      Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty
      oral melanomas, identified from the files of the participants, were reviewed in
      order to better understand the clinical features, histologic spectrum, and
      natural history of these perplexing lesions. Results confirmed that oral
      melanomas occur in adults almost three times more frequently in men than women
      and have a decided predilection for the palate and gingiva. Some lesions exhibit
      a clinically detectable and prolonged in situ growth phase, whereas others seem
      to lack this property and exhibit only or predominantly invasive characteristics.
      Recurrences, metastases, and death from tumor were characteristic of the follow
      up of a limited number of patients. Until definitive prospective data are
      collected that elucidate natural history, oral mucosal melanomas should be
      tracked separately from cutaneous lesions. All oral pigmented lesions that are
      not clinically diagnostic should be biopsied. Lesions with equivocal
      histopathologic features might be referred to as "atypical melanocytic
      proliferation" and should be excised. Recognition of lesions in an early in situ
      phase and aggressive treatment should have a favorable effect on prognosis. To
      enhance future or prospective study of these rare neoplasms, guidelines for
      reporting oral melanomas are suggested.

PMID- 9195623
TI  - Primary Hodgkin's disease of the mandible: a case report and review of the
      literature.
AB  - Extranodal presentation in Hodgkin's disease is uncommon and bone involvement is
      rare at diagnosis. However, late in the course of this disease, bone involvement
      may occur in 9% to 35% of the cases. The mandible is very rarely involved even in
      advanced stages with only seven such cases reported in the literature. Of these
      only one had primary Hodgkin's disease of the mandible. A second case is
      described in this report.

PMID- 9195624
TI  - Sclerosing mucoepidermoid carcinoma of the parotid.
AB  - Two cases of mucoepidermoid carcinoma of the parotid gland associated with
      extensive central sclerosis and peripheral lymphoid response are reported. This
      unusual but distinctive variant of mucoepidermoid carcinoma can be difficult to
      recognize and may be confused with chronic sialoadenitis or even metastasis to an
      intraparotid lymph node.

PMID- 9195625
TI  - Polymorphous low-grade adenocarcinoma: glial fibrillary acidic protein staining
      in the differential diagnosis with cellular mixed tumors.
AB  - Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland
      carcinoma arising primarily within the oral cavity. Most of these tumors are
      readily diagnosed; occasionally, however, they may be confused histologically
      with cellular mixed tumors. The difficulty stems from the bland cytologic nature
      of cellular mixed tumors and their organizational diversity, together with the
      irregular pushing growth at their interface with adjacent soft tissues, on
      histologic examination. Because of this diagnostic problem, we evaluated the use
      of glial fibrillary acidic protein localization in the differential diagnosis of
      polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral
      polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma)
      and twelve cellular mixed tumors were selected and stained for glial fibrillary
      acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin
      system and examined independently by each investigator. In addition, five tumors
      with limited material (three cellular mixed tumors and two polymorphous low-grade
      adenocarcinoma) from the consultation service of one author were evaluated using
      the same techniques. Two polymorphous low-grade adenocarcinoma stained positive
      in very focal areas and only in the epithelial component; staining did not occur
      in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed
      glial fibrillary acidic protein. Only one tumor did not express glial fibrillary
      acidic protein. In mixed tumors with only focal staining, the most helpful
      differential diagnostic feature was positive staining of the mesenchyme-like
      cells adjacent to epithelial nests. We did not find this latter staining pattern
      in any of the polymorphous low-grade adenocarcinoma.

PMID- 9195626
TI  - National survey of endodontists and selected patient samples: infectious diseases
      and attitudes toward infection control.
AB  - A survey was conducted of 591 patients from endodontic practices located in six
      large municipalities in the United States. A comparison was made between the self
      reported incidence of transmissible diseases from patients medical histories to
      national statistics for the incidence of hepatitis B, herpes, tuberculosis, and
      HIV/AIDS. A national survey of 422 endodontists was also conducted. This survey
      was used to determine the beliefs and attitudes of practicing endodontists toward
      infection control techniques and infectious diseases. Compared with previous
      surveys, a trend toward increasing use of the hepatitis B vaccine, gloves, and
      greater acceptance of medically compromised patients was found.

PMID- 9195627
TI  - Surgical treatment of a lateroradicular lesion on an invaginated lateral incisor
      (dens in dente).
AB  - The complex anatomy of invaginated teeth makes their endodontic treatment
      difficult. The case described here reports the successful management of an
      invaginated tooth presenting with a lateroradicular lesion. After the root was
      surgically exposed and the radicular defect was cleaned, gutta percha was sealed
      with a zinc oxide eugenol cement, heat-compacted under 5 degrees, and then cold
      burnished. The osseous cavity was filled with Biocorail. Radiographs at 1 month
      and 5 years show periapical healing with osseous formation. This procedure,
      resulting in minimal loss of hard tissues, permitted retention of the tooth.

PMID- 9195628
TI  - Radiographic and histologic periapical findings of root canal treated teeth in
      cadaver.
AB  - The success of root canal treatment can be subjectively evaluated both clinically
      and radiographically. Normally, the recall radiograph is the main factor in
      evaluating success or failure. OBJECTIVES: This study evaluated periapical areas
      of root canal treated teeth by correlating radiographic and histologic findings.
      STUDY DESIGN: Jaws were resected from cadavers and radiographed. Those teeth that
      had received root canal treatment were evaluated for success or failure based on
      radiographic criteria. Teeth and surrounding bone were then removed en bloc and
      prepared for light microscopy. Untreated teeth without periapical pathosis were
      examined as controls. RESULTS: Root canal treated teeth classified as failures
      were found to consistently have inflammatory resorptive lesions at the
      periapices. In contrast, those treated teeth classified as radiographically
      successful showed varying reactions ranging from normal uninflamed to mildly
      inflamed. CONCLUSIONS: Those classified as failure showed consistent
      inflammation. However, the majority of our examined treated teeth were
      radiographically normal and exhibited no periapical inflammation.

PMID- 9195629
TI  - Morphologic analysis of odontogenic cysts with computed tomography.
AB  - PURPOSE: The purpose of this study was to analyze the effects of lesion site and
      epithelial keratinization on the morphologic characteristics of odontogenic cysts
      and clarify determinate factors for cyst morphology. MATERIAL AND METHODS:
      Computed tomographic images of 92 odontogenic cysts were analyzed: 31 primordial,
      31 dentigerous and 30 radicular. Thirty-four cysts were located in the maxilla (6
      primordial, 10 dentigerous, and 18 radicular) and 58 in the mandible (25
      primordial, 21 dentigerous, and 12 radicular). Histologically, 31 cysts showed
      epithelial keratinization (18 primordial and 13 dentigerous). No keratinization
      was seen in radicular cysts. The morphologic features of cysts were assessed by
      measuring long length parallel to dental arch and short length vertical to it and
      calculating the long/short ratio. In addition, the computed tomography pattern of
      the cyst was classified into unilocular, lobulated, and multilocular patterns.
      Appearance of the sclerotic rim and surrounding cortex were classified into three
      and four patterns respectively to evaluate the developmental features of the
      cyst. RESULTS: As a whole, the long length of the primordial cysts was
      statistically larger than the other two cyst groups and resulted in a larger
      long/short ratio. Statistical differences of CT pattern were also seen among cyst
      groups. There was no preference in any cyst group for the appearance of the
      sclerotic rim and cortex. There were statistical differences between maxilla and
      mandible in short axis and long/short ratio. The maxillary cysts generally showed
      round shapes irrespective of their histologic characteristics. A multilocular
      pattern was more frequent in the keratinized group of mandibular primordial
      cysts. In dentigerous cysts, a multilocular pattern was seen only in the
      keratinized group and the long/short ratio was statistically larger; cyst shape
      was elliptical along the long axis. CONCLUSION: Our results demonstrated
      morphologic differences of odontogenic cysts caused by lesion site and
      keratinization. The dentigerous cyst with predominant keratinization should be
      included in the primordial cyst (odontogenic keratocyst) group.

PMID- 9195630
TI  - Digitizing of radiographs with a roller-type CCD scanner.
AB  - OBJECTIVES: Roller-type scanners can be used to digitize radiographs. This study
      evaluated the physical performance of a roller-type scanner with regard to
      dynamic range, scan reproducibility, and homogeneity. METHODS: A VXR-12 (Vidar
      System Corp., Herndon, Va.) roller-type scanner with imaging editing software
      Paint Shop Pro (JASC Inc., Minnetonka, Minn.) was used to digitize a step tablet
      image on Kodak T-MAT G films (Kodak, Rochester, N.Y.). The step tablet image was
      scanned at various locations and with different scanning settings. The pixel
      values of the resulting image were analyzed. The step tablet image was also
      scanned by a Wellhofer WD 102 Filmdensitometer (Wellhofer Dosimetrie,
      Schwarzenbruck, Germany) to measure the optical densities of the steps on the
      film for comparison. RESULTS: With the use of the default scanning settings the
      digitized images had pixel values distributed in a similar dynamic range to that
      of the film densitometer. This scanner produced consistent images with different
      scanning positions, different orientation of the images, and different power
      states of the scanner. CONCLUSIONS: This roller-type scanner has a similar
      dynamic range to that of the film densitometer. The operating condition of the
      scanner is stable, and the resulting image is not significantly affected by the
      scanning positions. This type of scanner should be suitable for digitizing dental
      x-ray films, although the limiting scanning resolution might not be sufficient
      for some diagnostic purposes.

PMID- 9195631
TI  - Comparison of a photostimulable phosphor system with film for dental radiology.
AB  - This study compared the imaging performance of a photostimulable phosphor system
      with E speed film for dental radiography. The response of each imaging system was
      measured as a function of radiation exposure. Measurements were also made of
      imaging performance in terms of the limiting spatial resolution and low contrast
      detectability. Photostimulable phosphors had a wider dynamic range in comparison
      with film. The limiting spatial resolution of the photostimulable phosphor was
      approximately 6.5 lp/mm and independent of image magnification. For film, the
      limiting spatial resolution was in the range 11 to 20 lp/mm depending on image
      magnification. At the same radiation exposure, low contrast detectability of the
      photostimulable phosphor was superior to that of film. Major benefits of
      photostimulable phosphor systems include the elimination of chemical processing
      and an improved low contrast detectability performance.

PMID- 9195632
TI  - Human articular cartilage storage in cell culture medium: guidelines for storage
      of fresh osteochondral allografts.
AB  - The viability of transplanted articular cartilage is one of the determinants of
      outcome following the transplantation of osteochondral allografts. Disappointing
      results from cryopreservation have led to the practice of fresh transplantation
      of articular segments, especially for posttraumatic defects. To date, no studies
      have demonstrated in vitro viability rates for refrigerated human cartilage
      awaiting transplantation. This study evaluates the effects of storage on the
      viability of human chondrocytes using cell culture medium. Human articular
      cartilage obtained from notchplasties was stored for up to 48 hours in cell
      culture medium. Radioactive 35S-sulfate uptake was determined at 0, 24, and 48
      hours, as a measure of protein, synthesis, and chondrocyte viability. Specimens
      were stored at 4 degrees C in culture medium. Results showed an average decrease
      in 35S-sulfate uptake of 0.8% at 24 hours and 6.4% at 48 hours, indicating a high
      level of chondrocyte viability after refrigeration. Because transplantation
      typically is performed within 24 hours of tissue harvest, it appears that nearly
      100% of chondrocytes should survive fresh transplantation.

PMID- 9195633
TI  - Snowboard traumatology: an epidemiological study.
AB  - In the past 10 years, snowboarding has become a popular winter sport among young
      people, and the number of accidents has increased proportionately. The incidence
      of traumas from snowboarding is shown to be 4 to 6 for every 1000 medical
      examinations, which is similar to that of downhill skiing. However, other
      important statistical differences exist between the two sports. This study of 106
      snowboarding-related injury cases analyzes the epidemiology of these injuries in
      Italy. Results found that 45.1% of injuries are located in the upper limbs and
      that significant advantages are obtained with the introduction of guards to
      protect the upper limbs during descent. Serious ligament injuries to the knee are
      more rare in snowboarding than in downhill skiing. In both sports, injuries are
      more common with rigid boots, which lead to a higher incidence of injury to the
      upper limbs. Finally, a high percentage of injury to beginners was found in this
      study. Training courses for those who are considering taking up the sport of
      snowboarding could significantly lower their risk of trauma.

PMID- 9195634
TI  - Anterior shoulder dislocation reduction technique--revisited.
AB  - Acute anterior shoulder dislocations are extremely painful conditions that force
      patients to present to emergency rooms or physicians' offices immediately. The
      diagnosis usually is established through a careful history and examination, and
      may be confirmed by appropriate radiography. The immediate treatment objective is
      to achieve reduction as early as possible, preferably through a closed reduction
      method with the least discomfort. Current methods of reduction are based on
      either traction or leverage maneuvers, with each having its own merits and
      disadvantages. This article, however, revisits the subject by a comprehensive
      literature review. It addresses obstacles to reduction and reports a closed
      reduction technique for the acute anterior dislocations of the shoulder that uses
      both traction and leverage maneuvers simultaneously. In addition, the technique
      eliminates failing factors of current reduction methods such as the surgeons'
      weakening or slippery grip when using traction methods. It is expected, by virtue
      of the method, that it would reduce the chances for complications such as humeral
      shaft fractures as can occur in leverage maneuvers. This method addresses all
      potential anatomical and pathological features of acute anterior dislocations of
      the shoulder to facilitate an earlier and more comfortable reduction.

PMID- 9195635
TI  - Current concepts in the treatment of articular cartilage defects.
AB  - Over time, articular cartilage loses the capacity to regenerate itself, making
      repair of articular surfaces difficult. Lavage and debridement may offer
      temporary relief of pain for up to 4.5 years, but offer no prospect of long-term
      cure. Likewise, marrow-stimulation techniques such as drilling, microfracture, or
      abrasion arthroplasty fail to yield long-term solutions because they typically
      promote the development of fibrocartilage. Fibrocartilage lacks the durability
      and many of the mechanical properties of the hyaline cartilage that normally
      covers articular surfaces. Repair tissue resembling hyaline cartilage can be
      induced to fill in articular defects by using perichondrial and periosteal
      grafts. However, these techniques are limited by the amount of tissue available
      for grafting and the tendency toward ossification of the repair tissue.
      Autogenous osteochondral arthroscopically implanted grafts (mosaicplasty), or
      open implantation of lateral patellar facet (Outerbridge technique), requires
      violation of subchondral bone. Osteochondral allografts risk viral transmission
      of disease and low chondrocyte viability, in addition to removal of host bone for
      implantation. Autologous chondrocyte implantation offers the opportunity to
      achieve biologic repair, enabling the surgeon to repair the joint surface with
      autologous articular cartilage. With this technique, care must be taken to ensure
      the safety, viability, and microbial integrity of the autologous cells while they
      are expanded in culture over a 4- to 5-week period prior to implantation.
      Surgical implantation requires equal attention to meticulous technique. In the
      future, physiologic repair also may become possible using mesenchymal stem cells
      or chondrocytes delivered surgically in an ex vivo-derived matrix. This would
      allow in vitro manipulation of cells with growth factors, mechanical stimuli, and
      matrix sizing to allow implantation of mature biosynthetic grafts which would
      allow treatment of larger defects with decreased rehabilitation and morbidity.

PMID- 9195636
TI  - ACL injury patterns in women.

PMID- 9195637
TI  - Delayed repair of a quadriceps tendon.

PMID- 9195638
TI  - Reconstruction of the patellar tendon using a patella-quadriceps tendon
      autograft.

PMID- 9195639
TI  - Avulsion of the anterior inferior iliac spine.

PMID- 9195641
TI  - Radiologic case study. Madelung's deformity of the wrist.

PMID- 9195640
TI  - Infected total knee arthroplasty: review.

PMID- 9195642
TI  - The effect of psychosocial nursing intervention on the mood state of patients
      with implantable cardioverter defibrillators and their caregivers.
AB  - This study sought to determine whether mood state and psychosocial adjustment
      four months after implantable cardioverter defibrillator (ICD) placement were
      better for patients and caregivers who received a program of psychosocial
      interventions than for those who received usual postoperative care and follow-up.
      Thirty-four adult ICD recipients (17 experimental and 17 control) and their
      significant other (SO) caregivers were randomly assigned to an experimental or
      control group. The intervention consisted of weekly, postoperative telephone
      follow-up, evaluation and counseling by a psychiatric liaison nurse, and
      participation in an ICD support group. There were no significant differences
      between treatment and control groups on the outcome measures of adjustment
      (Profile of Mood States, Psychosocial Adjustment to Illness Scale). Outcomes were
      not associated with age, ejection fraction, length of hospital stay or family
      income, and there were no differences in outcomes based on gender, employment
      status, thoracotomy versus non-thoracotomy procedure, or shocked versus unshocked
      status. The results do not indicate that the extra time spent to provide
      individualized attention to these ICD recipients and their SOs was advantageous
      for the outcomes measured. Adaptation to the device may occur over time
      regardless of intervention.

PMID- 9195643
TI  - Collaborative care: improving patient outcomes in cardiovascular surgery.
AB  - Collaborative care, a multidisciplinary process to standardize and streamline
      care for selected case types, has gained momentum as a care delivery system in
      health care settings. The major goals of these programs are to improve the
      quality and continuity of care, while decreasing length of stay and cost. This
      article will describe key components, issues and challenges of developing,
      implementing and evaluating a collaborative care program for cardiovascular
      patients. The initial clinical path focused on bypass surgery, incorporating many
      of the aggressive bypass surgery recovery guidelines, such as short-acting
      anesthesia, same-day extubation and decreased laboratory blood analyses and test
      utilization. Issues that arose focused on patient selection, documentation,
      determining appropriateness for discontinuing paths and patient/family education.
      In regard to clinical outcomes, no significant differences were found in
      mortality or complication rates, such as postoperative bleeding, dysrhythmias and
      infection rates, between the clinical path group and a comparable group of non
      path patients. Both intensive care unit (ICU) and overall hospital length of stay
      were concomitantly reduced. Other examples of program evaluation are also
      described, such as variation and patient follow-up data, to highlight quality
      improvement initiatives that further improve quality of care and reduce length of
      stay for this patient population.

PMID- 9195644
TI  - Focus groups: an exciting approach to clinical nursing research.
AB  - The focus group interview is an exciting qualitative research design that is
      gaining popularity among nurse clinicians and researchers. This article provides
      a practical approach to designing and implementing focus groups. The authors' own
      research experience with post-coronary angioplasty patients is used as a model.

PMID- 9195645
TI  - Clinical trials update.

PMID- 9195646
TI  - Where women stand today in primary prevention of coronary heart disease.

PMID- 9195647
TI  - Do you have nursing professional liability insurance?--Part I.

PMID- 9195648
TI  - What's wrong with this atrial fibrillation?

PMID- 9195649
TI  - Patient-focused care for the ventilator-dependent patient.

PMID- 9195650
TI  - The irreducible perspectives of consciousness.
AB  - I argue that there is no mind-brain problem but rather that there are irreducible
      subjective-objective problems. These include the difference between "inside" and
      "outside" perspectives on neural states, the creation of subjective neural states
      with objectified outside objects, and awareness of the self as an object in the
      world. The origin of consciousness is traced to the development of meaning
      states, and I demonstrate how differing perspectives related to these states are
      mutually irreducible. For instance, neural states are spatiotemporally
      distributed when observed from the outside, while mental states are unified when
      experienced from the inside; from the inside neural states are experienced as
      outside of themselves; and qualia have a material reality only from the inside.
      Rather than positing a special substance or immaterial process theory of
      consciousness, it is argued that the apparent immateriality of mind is an
      artifact of the nature of the phenomenon and of the process of observation
      itself.

PMID- 9195651
TI  - Some neurophysiologic aspects of consciousness.
AB  - An anatomico-physiologic approach to consciousness is facilitated by recognizing
      that the various meanings of consciousness have in common a crucial core C
      variously called subjectivity, awareness, consciousness-as-such, or consciousness
      per se. A sharp distinction is made between the property C and the contents of
      consciousness, partial loss of which is typical of cerebro-cortical lesions. The
      neuronal mechanism producing subjectivity also acts as an attention-action
      coordinator, hence must have specific connectivity requirements. These
      requirements are best met by the thalamic intralaminar nuclei (ILN). Whereas
      large lesions elsewhere leave C undisturbed, quite small bilateral lesions in ILN
      engender immediate unresponsiveness. This combination of anatomic and neurologic
      evidence is bolstered by a variety of physiologic evidence leading to the
      conclusion that further investigations of the ILN, and their interaction with
      lower centers as well as cerebral cortex, are most apt to yield a better
      understanding of consciousness.

PMID- 9195652
TI  - Disorders of consciousness: differential diagnosis and neuropathologic features.
AB  - Disorders of consciousness present intriguing challenges to the neurologist and
      neurorehabilitation specialist. Assessment is constrained by the lack of reliable
      methods of assessing consciousness, and there are no treatment interventions
      known to influence the course of recovery from these conditions. In addition, the
      relationship between the clinical features associated with these disorders and
      their corresponding pathophysiologic substrate is also unclear. Our understanding
      of disorders of consciousness has not kept pace with the advances in
      neurosurgical management that have decreased mortality following severe injury.
      There is still considerable confusion regarding differential diagnosis and
      prognostication concerning states of severely altered consciousness. The purpose
      of this article is to discuss the content and neural basis of consciousness and
      to review the terminology most often used to describe altered states of
      consciousness. The neurobehavioral criteria for differentiating among specific
      syndromes associated with severe alterations in consciousness are presented.
      Representative case studies are utilized to illustrate the characteristic
      clinical profiles of coma, vegetative state, persistent and permanent vegetative
      state, minimally conscious state, akinetic mutism, and locked-in syndrome. Areas
      of ambiguity and controversy are emphasized and future directions for research
      are suggested.

PMID- 9195653
TI  - Epilepsy and consciousness.
AB  - Seizure activity has long been associated with alterations in consciousness.
      Philosophical and neurologic debates concerning the definition of consciousness
      have led to confusion regarding an adequate third person assessment of a
      subjective experience. In order to avoid these controversies, neurologic
      evaluation of consciousness has focused on operational definitions that permit an
      objective assessment of behavioral responses that are constituent functions of
      consciousness. Clinical experience has demonstrated that ictal and post-ictal
      alterations in consciousness may be associated with loss of selected behavioral
      responses depending upon the focus and spread of seizure activity. Ictal
      electrophysiologic studies and brain stimulation has assisted in determining the
      anatomic structures involved in specific behavioral alterations. Consciousness
      dependent mental activity can be modeled as a series of interactive parallel
      information channels that can be selectively disrupted at any stage of processing
      giving rise to ictal behavioral patterns. While such modeling falls to grasp the
      subjective nature of consciousness, it offers the clinical community an objective
      measure of those responses believed to be dependent on consciousness.

PMID- 9195654
TI  - Dreaming as delirium: a mental status analysis of our nightly madness.
AB  - Dreaming is characterized by formal visual imagery (akin to hallucination), by
      inconstancy of time, place, and person (akin to disorientation), by a scenario
      like knitting together of disparate elements (akin to confabulation), and by an
      inability to recall (akin to amnesia). Taken together, these four dream features
      are similar to the delirium of organic brain disease. By studying the brain
      during rapid-eye-movement (REM) sleep-the phase of sleep in which most dreaming
      occurs-we can begin to understand its basis in the altered neurophysiology of
      REM.

PMID- 9195655
TI  - Some interesting perturbations of the self in neurology.
AB  - In this review I discuss four neurological disorders that involve alterations of
      the self or self-awareness. These include the allen hand syndrome, asomatognosia,
      misidentification of the self in the mirror, and personal confabulation. In one
      way or another all of these inform us about the neurobiological basis of the
      self. It is suggested that mirror self-misidentification, asomatognosia, and
      personal confabulation are related syndromes. They are interpreted as examples of
      a perturbation in relatedness between the self and the environment related to
      delusional misidentification syndromes. The particular role of bilateral
      frontolimbic damage in producing disturbances of the self is discussed.

PMID- 9195656
TI  - Consciousness and attention.
AB  - This article addresses the relationship between attention and consciousness. I
      take consciousness to refer, at least in an approximate sense, to those thoughts,
      memories, sensations, and actions of which one is aware, whereas attention refers
      to those processes that modulate neuronal activity. This modulation may be
      achieved by virtue of linking or binding distinct neuronal populations or by
      selecting information for further processing. Thus, consciousness and attention
      are different but closely related in that attention provides the glue that binds
      processes and representations to the prevailing cognitive set, thereby rendering
      them conscious. In this context, then, attention may be viewed as a control
      process. A number of neurologic syndromes in which disorders of attention result
      in the fragmentation of consciousness are discussed. Finally, the anatomic bases
      of attention, both cortical and subcortical, are reviewed.

PMID- 9195658
TI  - The neural basis of aware and unaware forms of memory.
AB  - Information regarding the nature of phenomenal awareness in memory comes from a
      direct comparison of explicit and implicit memory tasks. Explicit memory tasks
      require conscious awareness of a prior episode, whereas implicit memory tasks do
      not. This paper reviews evidence regarding the neural basis of aware and unaware
      forms of memory as obtained from patient studies and functional neuroimaging
      work. These studies suggest the existence of a memory system centered in the
      medial temporal and frontal lobes that is dedicated to the storage and retrieval
      of episodes and several neocortical memory systems that are dedicated to the
      processing and representation of perceptual and semantic information. Different
      hypotheses are discussed as to how the phenomenal awareness that accompanies
      episodic memories may arise within the hippocampal-frontal memory system. These
      views have in common the notion that various forms of information need to be
      bound together to be retrievable as an aware memory, and that the hippocampus is
      critical to this binding function.

PMID- 9195657
TI  - Consciousness of perception after brain damage.
AB  - Disturbances of visual perception after brain damage provide clues to
      understanding consciousness and the brain. In this article we review six visual
      disorders in which perception and consciousness are dissociated as a result of
      brain damage: blindsight, implicit shape perception in apperceptive visual
      agnosia, covert recognition of faces in prosopagnosia, unconscious perception in
      neglect and extinction, implicit reading in pure alexia, and implicit object
      recognition in associative visual agnosia. We consider these six disorders from
      the standpoint of three main schools of thought concerning consciousness and the
      brain, namely a localized system for consciousness, consciousness as a state of
      integration, and consciousness as a property of graded representation. The
      findings suggest that these syndromes do not share a single mechanism and that it
      is conceivable that more than one explanation will be necessary both within and
      across syndromes. We conclude on the basis of the current evidence that it is
      unlikely that any single brain system is necessary for conscious awareness of
      perception that does not play a role in perception as well.

PMID- 9195659
TI  - Consciousness and the neurobiology of perceptual binding.
AB  - The brain processes information along specialized tracts that are separated
      across cortex. However, our visual experiences are of unified objects. How our
      perceptions become united into wholes even though all individual features that
      comprise them are distributed about the brain is the problem of perceptual
      binding. This article discusses ongoing neurophysiological research that connects
      perceptual awareness with 40 Hz neural oscillatory firing patterns. Three
      different experimental approaches for tying 40 Hz oscillatory firing patterns in
      cortex to perceptual experiences are examined: (1) the single cell and local
      field potential recordings of visual areas 17 and 18 which show synchronous
      firing patterns between noncontiguous cells with similar receptive fields; (2)
      MEG measurements of rapid thalamic bursting, indicating that the ILN might drive
      or otherwise contribute to the cortical oscillations; and (3) EEG recordings
      taken over the sensory areas of cortex demonstrating a higher level of neural
      coordination, suggesting that perceptual binding occurs at a higher level of
      organization entirely. As of this writing, a connection between any 40 Hz
      oscillatory patterns and perceptual binding or consciousness is tenuous at best.

PMID- 9195660
TI  - Freud and consciousness: the first one hundred years of neuropsychodynamics in
      theory and clinical practice.
AB  - Psychoanalysis emerged out of Freud's neuropsychologic studies of consciousness
      and cognition. This article describes the historical development of
      neuropsychodynamic theories of consciousness and personality, and traces their
      application to several neuropsychiatric syndromes of intense contemporary
      clinical interest. Even in this era of narrow syndromic differentiation and
      classification, an appeal is made for a more integrated approach to the
      evaluation and treatment of neurobehavioral syndromes.

PMID- 9195661
TI  - Recent work on consciousness: philosophical, theoretical, and empirical.
AB  - Broad-spectrum philosophical resistance to physicalist accounts of conscious
      awareness has condensed around a single and clearly identified line of argument.
      Philosophical analysis and criticism of that line of argument has also begun to
      crystallize. The nature of that criticism coheres with certain theoretical ideas
      from cognitive neuroscience that attempt to address both the existence and the
      contents of consciousness. Also, experimental evidence has recently begun to
      emerge that will serve both to constrain and to inspire such theorizing. The
      present article attempts to summarize the situation.

PMID- 9195662
TI  - Thus "conscious" does make cowards of us all: reassessing resuscitation.

PMID- 9195663
TI  - Normal language acquisition.
AB  - Long before they start talking, children are skilled at using eye contact, facial
      expression, and nonverbal gestures to communicate with other people. They also
      are able to discriminate speech sounds from an early age. Vocabulary learning
      builds on the child's knowledge about objects, actions, locations, properties,
      and stages gained as a result of sensorimotor development. Early word
      combinations allow children to express semantic relationships between these
      various referents. During the period from 2 to 4 years of age, children move from
      expressing their ideas in simple telegraphic speech to being able to ask
      questions, use negation, talk about past and future events, and describe
      complicated situations using sentences constructed according to complex
      grammatical rules.

PMID- 9195664
TI  - Developmental language disorders.
AB  - Developmental language disorders are among the most common disorders of childhood
      referred to the pediatric neurologist. This article presents an overview of
      developmental language disorders, a discussion of the definition of developmental
      language disorders, potential causal factors, and a description of possible
      subtypes of language disorders in children. The article concludes with a review
      of the pediatric neurologist's role in developmental language disorders and
      recommendations for assessment and management.

PMID- 9195665
TI  - Language disorders in children with autism.
AB  - Language development is delayed in most children on the autistic spectrum. The
      children are dysphasic as well as autistic. Comprehension and pragmatics are
      invariably affected. Lower level mixed receptive/expressive disorders involve
      phonological and syntactical processing, whereas higher level processing
      disorders involve semantics and formulation of discourse. In some children, lower
      level disorders may be so severe as to preclude speech, whereas in others
      phonology may be deficient in spontaneous production but not in repetition.
      Abnormal features of autistic language include aberrant prosody, immediate and
      delayed echolalia (scripts), and perseveration. Electrophysiological studies
      indicate that brainstem-evoked potentials are normal. Even in fully verbal
      individuals with autism, early and late cortical components of auditory, but not
      visual, event-related potentials are abnormal. Appropriate intervention must
      address language and behavioral issues. In children with severely defective
      auditory language, provision of visual language to supplement speech is
      essential.

PMID- 9195666
TI  - Acquired epileptiform aphasia.
AB  - The acquired epileptiform aphasias, with Landau-Kleffner's syndrome as the
      example, represent an important group of syndromes in our quest to understand the
      relationship between epilepsy, language, and behavior. The controversy that truly
      frames the literature on the acquired epileptiform aphasias is the role of
      epileptiform activity on language, behavior, and cognition. This review expands
      the model of Landau-Kleffner's syndrome to include two other encephalopathies
      with language and behavioral regression in association with an epileptiform
      electroencephalogram. Both of these encephalopathies, autistic epileptiform
      regression and disintegrative epileptiform regression, are associated with an
      acquired language disorder. The developmental period in which the acquired
      language disorder begins, the type of language disorder, and the location and
      type of the epileptiform activity are all important variables that may affect
      clinical manifestations and prognosis.

PMID- 9195667
TI  - Acquired aphasia in children.
AB  - Acquired childhood aphasia is rare but has important conceptual implications for
      developmental neuropsychology. The last 15 years have seen major changes in their
      clinical description, which have led to the awareness that the syndromes in
      acquired childhood aphasia are more similar to the syndromes in adult aphasia
      than previously thought. This article briefly discusses the definition and
      differential diagnosis of acquired childhood aphasia from the point of view of
      the child neurologist and adds new perspectives afforded by neurolinguistic
      examinations. It reviews the main causes and syndromes of acquired childhood
      aphasia. Prognosis is less favorable than usually supposed, in terms of both
      language sequellae and academic failure. Finally, suggestions regarding the basis
      for aphasic children's nonverbal deficiencies are presented.

PMID- 9195669
TI  - Evidence from imaging on the relationship between brain structure and
      developmental language disorders.
AB  - This article discusses findings using various imaging techniques regarding the
      neurological underpinnings of developmental language and learning disorders.
      Evidence from magnetic resonance imaging, functional magnetic resonance imaging,
      single photon emission spectroscopy, and positron emission tomography implicates
      the left perisylvian regions in the processing of phonemes and auditory
      information, as had been predicted from lesion data and from neurobiological
      theory. The areas of the planum temporale and angular gyrus have been found to be
      compromised in children and adults with dyslexia or language impairment. Emerging
      evidence suggests that these differences are also present in members of families
      with a history of developmental language disorders, which provides support for a
      transmittable, biological factor involved in such disorders. Dynamic imaging
      procedures are beginning to provide an understanding of the relationship between
      structure and function in normal and abnormal language acquisition.

PMID- 9195668
TI  - Language development in children with congenital strokes.
AB  - The congenital lesion population provides an excellent forum to investigate the
      issues of innate specialization and plasticity. Effects of early lesions on left
      and right hemisphere function reflect both the cognitive process under study and
      biological/neurological factors of lesion parameters and hemispheric maturation
      rates. In general, toddlers with both congenital left and right lesions show mild
      to moderate delays in language acquisition. School-age children with left
      hemisphere lesions have more problems with language and language-based academic
      skills than those with right hemisphere lesions, but the problems are subtle and
      do occur in both groups. This pattern stands in sharp contrast with the adult,
      who shows striking language deficits with acquired lesions only in the left
      perisylvian region. Thus, there is evidence in these studies of the immature
      nervous system for both innate specialization and plasticity, as well as a right
      hemisphere contribution to language acquisition and verbal cognition.

PMID- 9195670
TI  - Electrophysiological studies of language and language impairment.
AB  - The organization of language-relevant brain systems was examined in normally
      developing and language-impaired children. Atypical patterns of brain activity
      were observed in subsets of children with specific language impairment (SLI) for
      both sensory (auditory and visual) and language processing. However, it was not
      the same groups of children who displayed abnormalities across the different
      tasks. The results supported a multiple-factors and multiple-subtypes framework
      for interpreting the neurobiology of SLI. The roots of SLI were also considered
      in normal infants and late talkers in studies of primary language acquisition.
      These studies suggest that the organization of neural systems important in
      language acquisition display dramatic changes during this time. Some of these are
      linked to the attainment of language milestones and appear to be independent of
      chronological age. Moreover, abnormalities in the lateral organization of
      electrophysiological activity may help predict which late talkers will catch up
      and who will later display SLI. More generally, the event-related potential
      technique is a powerful tool in studying the neurobiology of language and
      language impairment.

PMID- 9195671
TI  - Remediation of children with developmental language disorders.
AB  - There is no single approach to intervention in children with developmental
      language disorders. Remedial approaches differ in that they are based on
      differing theoretical perspectives. Four theoretical frames are reviewed.
      Neuropsychologically driven remediation, which tailors intervention to a child's
      profile of cognitive and linguistic strengths and weakness, is emphasized.
      Concrete examples of compensatory techniques suited to specific profiles are
      presented.

PMID- 9195672
TI  - Diagnostic strategies for Pneumocystis carinii pneumonia.
AB  - Pneumocystis carinii is an opportunistic organism that is a common cause of
      pneumonia in immunocompromised patients. Its life cycle begins when cysts rupture
      and release sporozoites, which mature into trophozoites that eventually form
      cysts. The diagnostic methods for P. carinii pneumonia (PCP) have progressed from
      open lung biopsy to bronchoalveolar lavage (BAL) and induced sputum analysis
      (ISA). Detection of P. carinii organisms is done with various stains that
      highlight sporozoites, trophozoites, or the cyst wall. Noninvasive, cost
      effective methods to aid in the diagnosis of PCP have been proposed and include
      chest radiograph analysis, gallium scintigraphy, serum lactate dehydrogenase
      levels, CD4 lymphocyte counts, pulmonary function tests, arterial blood gas
      analysis, and exercise hemoglobin oxygen saturation measurements. Some
      investigators propose empiric treatment of PCP to reduce the number of
      bronchoscopies performed. Most physicians prefer to make a definitive diagnosis
      of PCP to ensure appropriate therapy.

PMID- 9195674
TI  - Pulmonary toxoplasmosis.
AB  - With the advent of the human immunodeficiency virus (HIV) epidemic, the worldwide
      incidence of infections caused by Toxoplasma gondii has been rising. In this
      article I discuss the pathophysiology, diagnosis, and treatment of toxoplasma
      pneumonia. Basic research is now directed at the relationship of this organism to
      its host cells and how pharmacological or immunologic manipulation of that
      relationship may treat or prevent primary or recurrent infection. In addition to
      the standard diagnostic methods for T. gondii infection, newer methods using the
      tools of molecular genetics and immune complex staining are discussed. Although
      it is known that standard therapy for T. gondii pneumonia should use the
      synergistic combination of pyrimethamine and a sulfa-based antibiotic, optimal
      prophylactic antibiotic combinations and dosing schedules for recurrent infection
      are still being investigated. By stressing primary prevention and appropriate
      prophylaxis against T. gondii infection, the incidence of toxoplasma pneumonia in
      the immunocompromised host may be minimized.

PMID- 9195675
TI  - Pleuropulmonary amebiasis.
AB  - Amebiasis is the third leading parasitic cause of death in the world.
      Approximately 500 million people worldwide are infected with Entamoeba
      histolytica. Invasive disease is more common in the immunosuppressed, pregnant
      women, children, and alcoholics. Amebic colitis and liver abscess are the most
      common intestinal and extraintestinal manifestations of E. histolytica infection.
      Pleuropulmonary complications occur almost exclusively in individuals with a
      liver abscess. Common pleuropulmonary complications include right-sided
      sympathetic effusions, empyema, basilar atelectasis, lung infiltration, and lung
      abscess. Bronchohepatic fistula is an unusual and distinctive problem
      characterized by expectoration of sputum that may resemble anchovy paste. Left
      hepatic lobe abscesses occasionally produce left-sided pleuropulmonary
      complications and may result in lethal rupture into the pericardium. Diagnosis is
      based on demonstration of the organism in clinical specimens; however, false
      negative microbiological study results commonly occur even with active infection.
      Serological studies can confirm the diagnosis in the appropriate clinical
      setting, and newer immunological tests on blood, fluid, and tissue specimens show
      promise. Metronidazole remains the treatment of choice, and although surgical
      drainage is contraindicated, percutaneous drainage of abscesses and empyema may
      occasionally be indicated.

PMID- 9195673
TI  - Treatment of Pneumocystis carinii pneumonia in adults with AIDS.
AB  - Trimethoprim-sulfamethoxazole remains the treatment of choice in patients with
      Pneumocystis carinii pneumonia (PCP) requiring intravenous therapy. Those
      patients who require intravenous therapy who cannot tolerate or who fall therapy
      with trimethoprim-sulfamethoxazole may be treated with either pentamidine or
      trimetrexate (plus folinic acid), with or without orally administered dapsone.
      The toxicity of the former drug makes trimetrexate-based therapy the preferred
      second choice for parenteral use. Treatment with trimethoprim-sulfamethoxazole,
      dapsone-trimethoprim, or clindamycin-primaquine is approximately of equivalent
      efficacy, but variable toxicity, in patients with mild to moderate PCP for whom
      an oral route of administration is appropriate. Atovaquone, formulated as an oral
      suspension, is also effective, but, in the absence of additional data, must be
      considered as second line therapy. Adjunctive corticosteroid therapy is indicated
      for patients with [PAO2-PaO2] more than 30 mm Hg or PaO2 less than 70 mm Hg
      [corrected] while breathing ambient air in the absence of contraindications.
      Recognition of the apparent fungal nature of P carinii as well as improved
      understanding of the pathophysiology of PCP will lead to further improvements in
      antipneumocystis therapy.

PMID- 9195676
TI  - Pulmonary disease in selected protozoal infections.
AB  - Protozoa of the phylum Apicomplexa, including the genera Plasmodium, Babesia,
      Toxoplasmosis, and Cryptosporidium, are a group of closely related organisms that
      seldom cause pulmonary disease. All but Babesia are members of the subclass
      Coccidiasina ("Coccidians"). (The fungal organism Coccidioides immitis, a
      frequent cause of pulmonary disease in endemic areas, was first believed by
      Rixsford and Gilchrist to be a member of the subclass Coccidiasina; hence its
      name, meaning coccidioidal-like). Some species, such as Toxoplasma gondii,
      occasionally cause pulmonary disease by directly infecting lung parenchyma,
      whereas others, such as Cryptosporidium and Microsporidium, can be occasionally
      visualized in respiratory secretions or lung biopsy specimens, but their role in
      causing respiratory disease in human beings is more questionable. In contrast,
      pulmonary disease associated with infections caused by Malaria and Babesia is
      often the result of a systemic inflammatory response.

PMID- 9195677
TI  - Pulmonary manifestations of strongyloidiasis.
AB  - Strongyloides stercoralis (SS) is endemic in tropical and subtropical areas
      worldwide and in the southeastern United States. The lifecycle of SS is both
      unique and complex. Human infection begins with the penetration of skin by
      filariform larvae that migrate hematogenously to the lungs. Larvae then ascend
      the airway, are swallowed, and mature in the gut. Unlike other nematodes, SS can
      autoinfect the same host and persist for decades. Categorization of infection
      includes acute, chronic-uncomplicated, and disseminated forms. Clinical
      manifestations depend on the particular organs involved. Fifteen to thirty
      percent of chronically infected people may be asymptomatic. On the other hand, SS
      may cause the adult respiratory distress syndrome, septic shock, and death. The
      diagnosis of SS infection is suspected in patients from endemic areas who have
      blood eosinophilia, and gastrointestinal or pulmonary symptoms. A definitive
      diagnosis is established by demonstration of SS larvae in stool, body fluids, or
      tissues. A presumptive diagnosis of SS infection can be achieved by serology.
      Thiabendazole is the mainstay of treatment, but repeat doses may be necessary if
      the parasite is not initially eradicated. The low incidence of disseminated SS in
      areas endemic for both SS and AIDS is surprising and unexplained.

PMID- 9195678
TI  - Ascariasis and hookworm.
AB  - Ascariasis and hookworm (ancylostomiasis) remain the most common intestinal
      nematodes in the world with significant economic, social, and medical impact. An
      understanding of the transmission and pathogenesis of ascariasis and hookworm are
      necessary to recognize their clinical manifestations and to manage the pulmonary
      sequelae of infection. Transmission occurs predominantly in the tropics and rural
      areas where there is suboptimal sanitation, personal hygiene, and education
      regarding these parasites. Ascariasis generally occurs through hand-to-mouth
      ingestion of agricultural products or food contaminated with parasite eggs.
      Hookworm is transmitted through larval penetration of the skin. Larval pulmonary
      migration generally is asymptomatic. However, symptomatic pulmonary disease may
      occur with fever, cough, chest pain, hemoptysis, dyspnea, and wheezing due to (1)
      Loffler's syndrome, (2) the effects of larval tissue migration, (3) airway
      reactivity or bronchospasm, (4) infectious bacterial complications from parasitic
      migration and associated aspiration, and rarely (5) chronic eosinophilic
      pneumonia, transdiaphragmatic penetration, or symptoms of upper airway
      obstruction. Clinical evaluation shows pulmonary opacities on chest radiograph,
      peripheral blood eosinophilia, and larvae in respiratory or gastric secretions.
      Symptomatic treatment may be necessary with bronchodilators and systemic steroids
      or antibiotics for bacterial complications. The drug of choice is mebendazole
      (Vermox) 100 mg twice a day for 3 days. Alternatives include a single dose of
      pyrantel pamoate (Antiminth) 11 mg/kg (maximum dose, 1 g) or albendazole (Zentel)
      400 mg orally once. Invermectin (Mectizan) is available through the World Health
      Organization, and, in the United States, through the manufacturer on a
      compassionate-use basis. Ivermectin is as effective as currently available drugs
      against Ascaris but shows only partial efficacy against hookworms, which infest
      humans. Preventive measures, improvement of sanitary facilities, education, and
      school screening may be important in the endemic areas to control these parasitic
      infections.

PMID- 9195679
TI  - Dirofilaria, visceral larva migrans, and tropical pulmonary eosinophilia.
AB  - Helminthic infections are prevalent worldwide. The intestinal ascarid, Toxocara,
      the animal filarial parasite, Dirofilaria, and the human filarial parasite,
      Wuchereria or Brugia, produce an array of pulmonary disease in humans. Infections
      are common in temperate, tropical, and subtropical regions of the world.
      Pulmonary dirofilariasis is essentially an asymptomatic disease. Most cases are
      diagnosed accidentally after thoracotomy for a solitary pulmonary nodule presumed
      to be lung cancer. Clinical manifestations of toxocariasis or visceral larva
      migrans (VLM) are the result of allergic and inflammatory responses of the host,
      and manifest with airway reactivity, acute pneumonia, and persistent
      eosinophilia. VLM is a self-limited disease and specific treatment is rarely
      necessary. In acute cases, a short course of steroids reduces morbidity and
      mortality but preventive measures are more important in curbing toxocara
      infection. Tropical pulmonary eosinophilia (TPE) is the result of immunologic
      hyperresponsiveness to the human filarial antigen and eosinophils play a crucial
      role in its pathogenesis. Airway hyperreactivity, extreme eosinophilia, and
      pulmonary physiologic impairment are the characteristic features. Treatment of
      TPE with diethylcarbamazine results in dramatic amelioration of symptoms.
      However, low grade inflammation persists in a significant number of patients and
      can lead to chronic interstitial lung disease. Mass treatment of patients in
      certain endemic areas has been effective in eliminating TPE.

PMID- 9195680
TI  - Pulmonary paragonimiasis.
AB  - Paragonimiasis is a parasitic disease of carnivorous animals caused by trematodes
      of the genus Paragonimus. The epidemiology and life cycle of the parasite are
      reviewed, including intermediate hosts, and methods of infection in human beings.
      The pathogenesis of human disease is outlined. The clinical symptoms, which are
      often cause for an erroneous diagnosis of tuberculosis in many patients with
      paragonimiasis, are discussed. Radiographic findings, including those on computed
      tomography scans, are reviewed, and examples of classic chest radiographs are
      presented. The common laboratory abnormalities, including those seen on pleural
      fluid analysis, are briefly covered. The advantages and limitations of various
      diagnostic procedures, including parasitological, serological and intradermal
      skin tests, are detailed. Lastly, current therapy, including side effects and
      guidelines for patient treatment, are discussed and contrasted.

PMID- 9195681
TI  - Cardiopulmonary manifestations of schistosomiasis.
AB  - Three major schistosome species infect hundreds of millions of people worldwide.
      The majority of these infections are asymptomatic, but significant morbidity and
      mortality can occur as a consequence of ongoing egg deposition in host tissues.
      Acutely, transient chest radiographic abnormalities and nonspecific influenza
      like symptoms can occur, including cough. The most common chronic pathological
      sequelae of schistosomiasis are those of portal hypertension with Schistosoma
      mansoni or S. japonicum, and genitourinary tract obstruction with S. haematobium.
      In less than 5% of infections, schistosomal egg obstruction of the lung
      vasculature results in pulmonary hypertension and cor pulmonale. Limited data
      suggests that cardiopulmonary schistosomiasis is seen most often in S. mansoni
      infections. Hepatic fibrosis and portal hypertension appear to be a prerequisite
      to the development of schistosomal cor pulmonale caused by this species. The
      premortem diagnosis of cardiopulmonary schistosomiasis depends on the detection
      of viable schistosomal ova in stool or urine along with evidence of
      characteristic hepatic fibrosis and pulmonary hypertension. Although treatment
      with praziquantel can effectively eradicate all schistosomal infections with
      minimal toxicity, cardiopulmonary manifestations are not likely to be reversible
      given the chronic fibrotic tissue changes that are present.

PMID- 9195682
TI  - Echinococcus.
AB  - Echinococcosis (hydatid disease) is a zoonotic infection of human beings caused
      by the postlarval metacestode stage of the dog tapeworm, Echinococcus. Hydatid
      disease is more frequently the result of infection by Echinococcus granulosus and
      E. multilocularis species, which are more widely prevalent geographically than E.
      vogeli and E. oligarthus. The epidemiology, biology, and host-parasite
      relationships of echinococcal infection are discussed, and the clinical
      consequences of human infection are reviewed with particular emphasis on the
      pulmonary manifestations of the disease. The utility of serological and
      radiological techniques in diagnosis and management are reviewed. The efficacy of
      medical therapy and its relationship to the role of surgical intervention in the
      management of unilocular (cystic) and multilocular (alveolar) hydatid disease is
      discussed. Finally, the successes and failures of public health programs to
      control this zoonosis are noted.

PMID- 9195683
TI  - Normal aging and human physiology.
AB  - This article discusses the physiological changes that accompany normal aging and
      current understandings of how environmental factors interact with a person's
      genetic mechanisms to slow or speed up the aging process. Chronological age is
      contrasted with biological age to illustrate the different rates and extent of
      anatomical changes and functional declines observed in older people of the same
      age, behaviors that appear to delay or reduce the inevitable progression of
      sensescence, the extraordinary heterogeneity of the aging population, and the
      complexity of the processes responsible for the consequences of human aging.

PMID- 9195684
TI  - Normal aging and environmental effects on communication.
AB  - This article focuses on the role of communication in the successful adjustments
      and adaptations to normal aging by elders. It views communication as an essential
      tool for living safely and independently, for maintaining interests and a sense
      of purpose, for continuing important social and family relationships, and for
      exercising active control over quality of life and care. The discussion
      emphasizes the importance of physical and social environments to elders'
      communication efforts and suggests that an environmental approach to the
      communication problems of many elders may be more beneficial than the remediation
      of specific speech-language skills.

PMID- 9195686
TI  - Speech production of normally aging adults.
AB  - A number of changes in older adults' speech characteristics accompany aging. This
      article reviews the changes usually perceived in elders' speech, then focuses on
      several key components of older adults' speech that account for these changes:
      vowel productions, voice onset time and phoneme segment duration, and speaking
      rate. Although laryngeal factors are evident in older voices and associated with
      declining physiological conditions, certain changes are associated with advanced
      age.

PMID- 9195685
TI  - Normal aging and the multicultural population.
AB  - This article documents the dramatic increase expected in the number of people
      over 65 years of age who will be living in the United States during the first
      half of the 21st century and describes how the age, health, and ethnic
      differences of this expanding group will comprise an extremely heterogeneous
      subpopulation. Differences in how aging and the health problems that accompany it
      may be viewed are discussed in terms of cultural influences and traditions. It is
      suggested that such differences in a growing segment of the population that is
      likely to have increasing needs for speech-language pathology services in the
      years ahead could pose significant challenges for the profession.

PMID- 9195687
TI  - Discourse behaviors in older adults.
AB  - An overview of the changes in older adults' comprehension of language and
      discourse is provided before changes in production are discussed in some detail.
      Age-related changes in discourse production have been studied in terms of
      semantic skills, syntactic complexity, verbal fragmentation, information load,
      cohesion, macrostructural elements, and conversation. In spite of the
      heterogeneity in older adults' discourse behaviors, they have a tendency to use
      shorter, less complex sentences and more indefinite, ambiguous references.
      Nevertheless, the basic conversational skills of the normally aging elderly are
      usually well preserved.

PMID- 9195688
TI  - The aging voice.
AB  - A number of studies have found that listeners are often able to differentiate the
      voices of young and old speakers accurately. Following an overview of structural
      and functional changes found in studies of aging larynges, this article examines
      current findings on maximum phonation duration, voice quality, vocal
      jitter/shimmer, spectral noise, and fundamental frequency. Aging can affect vocal
      pitch, loudness, and quality, but such effects are highly variable across the
      aging population. Therefore, a thorough voice and medical examination is needed
      to isolate voice problems caused by vocal abuse or pathology from those due to
      normal aging. Pushing exercises may be a viable treatment option for those with
      age-related voice problems.

PMID- 9195689
TI  - Age-related effects on speech fluency.
AB  - This article provides a brief review of age-related changes in speech production
      before discussing fluency changes that have been found in aging, nonstuttering
      speakers. Most studies agree that old and young adults evidence similar
      frequencies of disfluency. The disfluencies of a 105-year-old woman were compared
      to the means of several geriatric groups whose average ages were more than 20
      years younger. Overall frequencies and types were similar. Thus, aging speakers'
      fluency does not appear to be more susceptible to breakdowns than that of younger
      speakers, although there is some evidence that elderly speakers become much more
      disfluent than younger speakers under stressful conditions.

PMID- 9195691
TI  - Does GB virus C ('hepatitis G virus') threaten the safety of our blood supply?

PMID- 9195690
TI  - Effects of aging on neuromotor processes of swallowing.
AB  - Isolated swallowing difficulties are present in a substantial percentage of
      elderly adults. Most have no known medical basis, although some may be caused by
      underlying, but undetected, medical conditions. Others may result from conditions
      that indirectly affect swallowing. After an overview of the neuroanatomy and
      neurophysiology of swallowing, this article reviews findings on changes in
      swallowing that accompany aging. Some of the differences reported have failed to
      be replicated consistently, and other changes are subtle, their significance
      unknown. Most studies, however, have found decreased sensitivity in both the oral
      and pharyngeal cavities. It is concluded that additional objective clinical
      measures are needed to isolate changes in swallowing due to age from those
      resulting from other causes. Clearly, further research is needed.

PMID- 9195692
TI  - Policies and procedures for the establishment of an allogeneic blood stem cell
      collection programme.

PMID- 9195693
TI  - Identification of HLA class II antigens as the targets of effector clones which
      may cause transfusion-associated graft-versus-host disease.
AB  - We established T cell clones, which were considered to be the possible cause of
      transfusion-associated graft-versus-host disease (TA-GVHD), from the peripheral
      blood lymphocytes (PBLs) of two patients. In both cases, several CD4+ cytotoxic T
      cell (CTL) clones were established. In case I, the target antigen of the
      established CD4+ clones was a DRB1*0403-related antigen serologically typed as
      HLA DR4, which was one of the patient HLA antigens. In case II, the target of
      four out of five established CD4+ CTL was a DRB1*1302-related antigen. One CD4+
      CTL clone showed cytotoxicity against cells carrying A*2402, B*4403, Cw*1403 and
      DPB1*0401. A monoclonal antibody (mAb) blocking study showed only anti-DP mAb
      inhibited the cytotoxicity of this clone. Thus, it might be considered that this
      clone recognizes HLA-DP with its binding peptides derived from either A*2402,
      B*4403, Cw*1403 or DRB1*1302. Our findings indicate that CD4+ CTLs may play
      important roles in the aetiology of TA-GVHD and that the antigens of patients
      recognized by donor-derived effector cells may not always recognize a single HLA
      antigen.

PMID- 9195694
TI  - Comparison of two blood cell separators in collecting peripheral blood stem cell
      components.
AB  - To ensure that a sufficient number of CD34+ cells are collected for an allogeneic
      blood progenitor cell transplant, the most effective blood cell separator should
      be used to collect peripheral blood stem cell (PBSC) components. We compared the
      effectiveness of two blood cell separators. We gave 29 healthy people 7.5 or 10
      micrograms kg-1 of granulocyte colony stimulating factor (G-CSF) daily for 5 days
      and collected one PBSC component with either a Fenwal CS3000 (n = 15) or a Cobe
      Spectra (n = 14) blood cell separator. The volume of blood processed was the same
      for each machine (8.4 +/- 1.0 L; range = 4.9-9.4 L for the CS3000 and 8.9 +/- 1.0
      L; range 6.7-10.9 L; P = 0.71). The components collected with the CS3000
      contained more mononuclear cells (39.6 +/- 21.9 x 10(9) compared with 26.9 +/-
      5.6 x 10(9), P = 0.02) and fewer neutrophils (1.38 +/- 1.88 x 10(9) compared with
      5.53 +/- 8.71 x 10(9), P = 0.001). The total number of CD34+ cells collected with
      the two instruments was the same (470 +/- 353 x 10(6) for the CS3000 and 419 +/-
      351 x 10(6) for the Spectra; P = 0.64) as was the number of CD34+ cells collected
      per litre of whole blood processed (55.9 +/- 42.0 x 10(6) L-1 compared with 45.9
      +/- 37.9 x 10(6) L-1; P = 0.59). The mononuclear cell collection efficiency was
      greater for the CS3000 (82.4 +/- 54.9% compared with 53.3 +/- 14.1; P = 0.04) but
      the CD34+ cell collection efficiencies were the same (87.4 +/- 61.1% for the
      CS3000 compared with 56.3 +/- 23.5% for the Spectra; P = 0.07). In conclusion,
      both blood cell separators collected components which contained large numbers of
      CD34+ cells, but those collected with the CS3000 contained fewer neutrophils and
      the CS3000 was more efficient at collecting mononuclear cells.

PMID- 9195695
TI  - Blood spillage during salvage.
AB  - Recovery of blood components by salvage was evaluated in a randomized laboratory
      investigation using donor whole blood. Three methods of salvage were studied;
      conventional red cell salvage, red cell salvage with continuous processing, and
      salvage by haemofiltration using recirculation through a 30,000-Da filter. Less
      than 10% of the haemoglobin was wasted during processing by all three methods.
      About half of the leukocytes were recovered with no significant difference
      between the techniques. The recovery of platelets was 15, 4 and 41% during
      salvage with conventional red cell centrifugation, continuous centrifugation
      processing and haemofiltration, respectively. In contrast with the other methods,
      haemofiltration gave a major recovery of albumin.

PMID- 9195696
TI  - Effects on complement activation of a new continuous autotransfusion system.
AB  - Allogeneic blood transfusions may subject patients to risks of infection and
      allergic reactions. Various techniques for transfusion of shed blood have been
      developed. The aim of this study was to evaluate a new continuous autotransfusion
      system (Fresenius CATS) as regards its impact on the complement system, and on
      erythrocytes and leucocytes. Eighteen consecutive patients undergoing hip
      replacement surgery were studied. Complement variables (C4d, factor Bb, C3a and
      terminal complement complex, SC5b-9) and free haemoglobin, haemoglobin,
      leucocytes, platelets, albumin and protein were determined in the patient's blood
      preoperatively, 1 min before the start of transfusion, 15 and 60 min after
      transfusion; and in the reservoir, in the waste bag and in the retransfusion
      blood. Increased concentrations of C3a and SC5b-9 were found in the collected
      reservoir blood (P < 0.05). The washing and centrifugation procedure reduced
      these concentrations (< 0.001). High levels of free haemoglobin were found in the
      collected blood as well as in the processed product. The median haemoglobin level
      in the processed blood was 260gL-1 (range 104-289gL-1). Inflammatory mediators
      from the complement cascade are removed by continuous autotransfusion technique.
      The processed blood contains high levels of free haemoglobin.

PMID- 9195697
TI  - Length of survival after perioperative transfusion.
AB  - To describe the post-transfusion survival of an entire, geographically defined
      population, we observed all residents of a US county who underwent perioperative
      transfusion before and after the introduction of a large autologous transfusion
      programme. We enrolled 444 and 1540 county residents, transfused in 1981 and in
      1986-88, respectively. Complete follow-up (until death or for 5 years) was
      available on 1960 patients (98.8%). Of patients transfused in 1986-88, 67.6% were
      alive at 5 years, having survived for a mean (+/- SE) period of 46.15 (+/- 0.575)
      months. The survival statistics were 66.2% and 46.09 (+/- 1.047) months,
      respectively, for patients transfused in 1981 (P = 0.8424). Transfusion in 1986
      88 vs. 1981 (with 615 [40%] vs. six [1.3%] patients receiving some autologous
      blood) did not have an effect on survival (P = 0.3892), following adjustment for
      age, gender, transfusion dose, receipt of a single-unit transfusion and
      transfusing surgical service. We conclude that the survival of an entire,
      geographically defined transfused population is substantially longer than that
      reported previously for patients referred to tertiary-care medical centres. The
      aggregate 5-year survival of patients transfused in 1981 and in 1986-88 does not
      differ, despite differences in patient case-mix and in perioperative transfusion
      practice, particularly as it relates to autologous blood usage.

PMID- 9195698
TI  - The presence of free infectious cytomegalovirus (CMV) in the plasma of donated
      CMV-seropositive blood and platelets.
AB  - An in vitro study was carried out to determine the presence of free infectious
      CMV in the supernatant of donated units of blood and platelets which were known
      to be CMV seropositive. One sample was taken from each of 10 units of CMV
      seropositive platelet donations which were 4 days old. Ten units of seropositive
      blood were sampled at intervals over their storage lifespan. Each sample was
      divided into two and thrombin was added to one of them. The samples were all
      prepared by centrifugation. The resulting supernatant from the clotted samples
      was used in in vitro culture studies using the MRC-5 cell line to ascertain the
      infectivity of the samples. The anticoagulated supernatants were subjected to PCR
      analysis to detect the presence of free genomic CMV DNA. All of the units of
      blood and platelets tested positive for the presence of genomic CMV DNA by PCR.
      Seven out of the 10 units of blood were culture positive from samples taken 3-4
      weeks into their shelf-life. None of the platelet samples was culture positive.
      The cultures of supernatants taken from seropositive blood were negative when the
      units were fresh, but further into their storage life, the cultures became
      positive, indicating that infectious material was released into the supernatant
      during storage, presumably due to the breakdown of intact white cells.

PMID- 9195699
TI  - A comparison of monoclonal antibody immobilization of platelet antigen (MAIPA)
      and immunobead methods for detection of GPIIb/IIIa antiplatelet antibodies in
      immune thrombocytopenic purpura.
AB  - In this study we have compared two assays for the detection of autoantibodies
      GpIIb/IIIa, platelet bound and in serum, in immune thrombocytopenic purpura
      (ITP). Both assays were found to have a similar sensitivity, but the monoclonal
      antibody immobilization of platelet antigen (MAIPA) assay was more reproducible
      than the immunobead assay. The MAIPA and immunobead assay demonstrated an 81%
      concordance of results for serum antibody detection and a 78% concordance for
      platelet-associated antibody detection, with an 8-12% incidence of false positive
      or negative results.

PMID- 9195700
TI  - Comparison of Fy(b) status as determined serologically and genetically.
AB  - Comparison of the serologically determined phenotype and the genotype of samples
      as defined by PCR-RFLP indicated a significant percentage of discrepancies on
      analysis of serologically defined Fy(a + b-) samples. An investigation of these
      discrepancies has shown that the serologically determined phenotype of the
      samples varies with respect to the reagent used but that the PCR-RFLP assay gives
      reliable results for all the samples investigated. The samples which yielded the
      discrepant results were further investigated and the results indicated weakened
      expression of the Fyb antigen. This may arise by a method similar to the
      expression of Fyx although we found the incidence of these samples to be much
      higher than that reported for Fyx. These results may have important implications
      for the routine testing of blood donations, particularly in situations where the
      unit is to be transfused to a patient who has previously formed an anti-Fyb.

PMID- 9195702
TI  - Guidelines for pre-transfusion compatability procedures.

PMID- 9195701
TI  - Royal College of Physicians of Edinburgh/Royal College of Obstetricians and
      Gynaecologists consensus conference on anti-D prophylaxis 7 & 8 April 1997.

PMID- 9195703
TI  - Are guidelines for use of gamma irradiation for the prevention of transfusion
      associated graft-versus-host disease adequate for newborns?

PMID- 9195704
TI  - Toxoplasma gondii recombinant antigens H4 and H11: use in ELISAs for detection of
      toxoplasmosis in swine.
AB  - Toxoplasma gondii recombinant antigens H4 and H11 were assessed for their
      potential for use in ELISA for diagnosis of toxoplasmosis in swine. The antigens
      were evaluated with sera from young pigs experimentally infected with T. gondii.
      Results were compared with ELISAs based on a native T. gondii antigen extract.
      Although recombinant antigen ELISAs showed a sharp rise in response with some
      sera very early after infection, they were relatively non-reactive with late
      (chronic) infection sera.

PMID- 9195705
TI  - Effect of diminazene aceturate on the infectivity and transmissibility of drug
      resistant Trypanosoma congolense in Glossina morsitans centralis.
AB  - To determine the duration after treatment of cattle with diminazene aceturate
      that the drug influences the tsetse infectivity and transmissibility of a drug
      resistant Trypanosoma congolense, six Boran cattle were infected with T.
      congolense IL 3338 via the bites of Glossina morsitans centralis. At the first
      peak of parasitaemia, different groups of 120 teneral G. m. centralis were fed on
      one occasion on each animal, 1 h before treatment with diminazene aceturate at a
      dose of 3.5 mg kg-1 body weight. Thereafter, on Days 1, 2, 3, 7, 14 and 21 after
      treatment, six different groups of 120 teneral G. m. centralis were similarly fed
      on each animal. After 28 days maintenance on uninfected goats, all the flies were
      probed onto slides at 37 degrees C to identify those extruding metacyclic
      trypanosomes. Flies with mature infections from each group were then fed on one
      occasion on individual mice to determine the transmissibility index. After
      dissection of flies on Day 30 after their feed on the cattle, the mean mature (+/
      SE) infection rates in the seven groups of flies were 32.1 +/- 2.2, 1.0 +/- 0.7,
      0.4 +/- 0.4, 0.5 +/- 0.3, 20.0 +/- 1.7, 33.3 +/- 2.2 and 23.4 +/- 2.0% for flies
      fed on Days 0, 1, 2, 3, 7, 14 and 21 after treatment with diminazene,
      respectively. The transmissibility rates for the seven groups ranged from 94 to
      100%. Thus, when cattle were infected with a diminazene-resistant T. congolense,
      treatment with diminazene aceturate caused a substantial reduction in the ability
      of the trypanosomes to establish mature infections in tsetse for at least the
      first 7 days after treatment. In contrast, no significant effect on the
      transmissibility of the parasites to mice was observed at different intervals
      after treatment.

PMID- 9195706
TI  - Effect of different cytokines on the growth of Trypanosoma congolense cultured
      under axenic conditions.
AB  - We previously reported that susceptible BALB/c mice had high amounts of
      interleukin-4 (IL-4) and interleukin-10 (IL-10) in their plasma after infection
      with Trypanosoma congolense and the levels of these cytokines decreased
      dramatically after berenil treatment. These observations instigated us to
      speculate that these cytokines might be directly affecting the growth of these
      parasites. Previously, it was reported that interferon gamma (IFN-gamma) had a
      growth stimulatory effect on T. brucei brucei in vitro. Although recombinant
      murine IL-4, IL-10 and IFN-gamma used in this study were biologically active,
      none of these cytokines had any growth stimulatory or inhibitory effect on T.
      congolense in vitro.

PMID- 9195707
TI  - Babesial antibody dynamics after cattle immunisation with live vaccines, measured
      with an indirect immunofluorescence test.
AB  - The efficacy of vaccination of Argentinean cattle against babesiosis and
      anaplasmosis using live immunogens was tested to detect specific antibodies in
      samples obtained about 60 days after vaccination. Under these conditions a higher
      than expected proportion of cattle failed to show antibodies against Babesia
      bigemina. Therefore, a study was designed to evaluate if this failure was due to
      insensitivity of the routine test to detect antibodies to B. bigemina or to lack
      of infectivity of the live vaccine. Four groups (G) of cattle were each
      inoculated subcutaneously with 10 million Babesia bovis (vaccinal strain R1A), 10
      million B. bigemina (vaccinal strain S1A) and 10 million Anaplasma centrale
      (strain M1). G1 and G2 consisted of ten Angus bulls 20-24 months old and ten
      Angus bulls 15-18 months old, respectively; G3 and G4 consisted of ten and 16
      Holstein 1-month-old male calves, respectively. Blood samples were obtained on
      days 0, 10, 20, 30, 40, 50 and 60 after vaccination and the sera were analysed
      with an indirect immunofluorescent (IFA) test to detect antibodies to B. bovis
      (baseline dilution for a positive result 1:60) and B. bigemina (baseline dilution
      1:120). Positive IFA titres were considered as evidence of the infectivity of the
      Babesia vaccinal strains contained in the vaccine. All Angus bulls were found
      positive to antibodies against both Babesia species, by day 20 (B. bovis) and day
      30 (B. bigemina), whereas 10-25% of Holstein calves were negative throughout. The
      partial lack of vaccine infectivity in the calves was considered to be a
      consequence of innate resistance of young calves to Babesia. Antibody titres to
      B. bovis and B. bigemina declined by day 60 after vaccination. However, all
      cattle that were positive to B. bovis antibodies on day 50 were still positive to
      the IFA test 10 days later while 10%, 30% and 12% of cattle of G1, G2 and G3 that
      were positive to B. bigemina antibodies on day 50 after vaccination were found
      negative to the IFA test on day 60. In future, samples taken on days 40-50 will
      be used for detection of B. bigemina antibodies in vaccinated cattle, on day 60
      for A. centrale and on either occasion for B. bovis. The reaction to the
      inoculation of B. bigemina S1A strain appears to lag behind the reaction to B.
      bovis R1A strain. It is not certain if this is a normal reaction to this B.
      bigemina strain or the result of interaction with the B. bovis strain.

PMID- 9195708
TI  - Isolation of the trichomonad Tetratrichomonas buttreyi (Hibler et al., 1960)
      Honigberg, 1963 in bovine diarrhoeic faeces.
AB  - A trichomonad was found in the faeces of a heifer with watery diarrhoea. It was
      classified as Tetratrichomonas buttreyi according to its morphology as revealed
      by scanning electron microscopy. This flagellate was successfully maintained in a
      cysteine-peptone-liver medium. It is, to our knowledge, the first report of
      Tetratrichomonas buttreyi in Spain. This trichomonad appears to be a
      nonpathogenic commensal which often proliferates in fluid faeces.

PMID- 9195709
TI  - Eimeria acervulina: influence of corticosterone-induced immunosuppression on
      oocyst shedding and production characteristics in broilers, and correlation with
      a computer simulation model.
AB  - An experiment was conducted to investigate the effects of immune responsiveness
      on excretion of oocysts after E. acervulina infection and subsequent effects on
      production characteristics of broilers (Gallus domesticus). These effects were
      determined in broilers repeatedly infected with 2.85 x 10(3) oocysts of E.
      acervulina and treated with various dosages of corticosterone in the diet (0, 10,
      20 and 30 p.p.m.). Corticosterone treatment did not have an effect on the peak
      oocyst excretion, although it was administered from 4 days before initial
      infection. The number of oocysts excreted shortly after the peak and the length
      of the excretion period were increased in corticosterone-treated groups. The
      absence of a difference in peak oocyst excretion was ascribed to the existence of
      a time-lag between first contact with the parasite and rate of development of
      protective immunity. In a recently developed computer simulation model this
      period was assumed to be 5 days. Assuming that immunosuppression, through
      corticosterone, is only effective when protective immunity is in operation, the
      results indicate a time-lag of at least a few days, which supports the inclusion
      of such a time-lag in the computer simulation model. General immunosuppressive
      effects of the corticosterone treatment, monitored by antibodies and mitogen
      induced lymphocyte stimulation confirmed that immunosuppression occurred shortly
      after medication started. Infection did not have a significant influence on
      production characteristics in animals without dietary corticosterone. However,
      with increasing corticosterone levels the negative effects of infection on
      production also increased.

PMID- 9195710
TI  - Vaccination against Eimeria magna coccidiosis using spray dispersion of
      precocious line oocysts in the nest box.
AB  - Coccidiosis mostly affects young rabbits just after weaning (5- to 6-week-old
      animals). Prevention of this disease must therefore be initiated before weaning.
      'Precocious lines', derived from field species display good immunogenicity,
      though not pathogenic when administered at the right dose. In the present work,
      we tested the vaccination method of the whole litter at 25 days of age by spray
      dispersion of oocysts of a precocious line of Eimeria magna in the nest box.
      Three doses were tested, d1 = 4 x 10(2) oocysts, d2 = 4 x 10(3) oocysts, d3 = 4 x
      10(4) oocysts. The animals were challenged individually with 10(4) oocysts of a
      wild strain of E. magna at 35 days of age, 5 days after weaning. The oocyst
      output and weight gain were recorded after vaccination and after challenge. The
      vaccinated animals did not display any vaccine reaction. The dose d3 was totally
      effective on oocyst output and on weight gain under our experimental conditions.
      As our challenge conditions were severe, we think that a lower vaccine dose could
      be used. This method proved to be efficient, and quick and easy to use because it
      did not require animal manipulation.

PMID- 9195711
TI  - The influence of supplementation with cotton seed cake on the resistance of
      Ugandan goats to primary and secondary challenges with Trypanosoma congolense and
      on their response to treatment.
AB  - The present study investigated the influence of supplementation with cotton seed
      cake on the resistance of the Small East African breed of goats to primary and
      secondary challenges with Trypanosoma congolense and on their response to
      chemotherapy with diminazene aceturate. The supplemented group received 300 g of
      cotton seed cake per day in addition to about 500 g of fresh napier grass which
      was available to the unsupplemented group. It was observed that the supplemented
      infected (SI) group tended to sustain higher intensities of parasitaemia than the
      unsupplemented infected (USI) group particularly during the primary challenge and
      both groups showed longer prepatent periods to secondary challenge than to
      primary challenge. Infection caused a significant reduction in the rate of live
      body weight gain in the USI group compared with the unsupplemented control (USC)
      group whilst the SI group grew at the same rate as the supplemented control (SC)
      group. This effect was observed both during primary and secondary challenges.
      Following primary challenge, both infected groups developed similar degrees of
      anaemia, but the packed red cell volume (PCV) levels in the SI group improved
      towards the end of the first challenge and were also significantly higher than
      those of the USI group during the second challenge. After treatments at 56 and
      126 days after infection (DAI), the greatest response was observed in PCV values.
      The response of the SI group was superior to that of the USI group and by 4 weeks
      after treatment the PCV values of the SI and SC groups were similar while those
      of the USI group were significantly lower than those of the USC group. It is
      concluded that supplementation with cotton seed cake plays an important role in
      the rate of live weight gain, and rate of recovery from anaemia produced by
      trypanosome infection in goats.

PMID- 9195712
TI  - A general review on the prevention and treatment of Theileria annulata in China.
AB  - A review is given of the prevention and treatment of Theileria annulata infection
      of cattle in China. Primaquine phosphate has been shown to be an effective drug
      for the elimination of gametocytes of T. annulata and an attenuated strain of
      virulent parasites is used as a vaccine. This vaccine has proved to be 100% safe
      and over 90% effective. Since the use of these two methods of control, the
      disease caused by T. annulata in cattle in China has been controlled.

PMID- 9195713
TI  - Use of an in vitro infectivity assay in comparison with histological techniques
      in the study of Theileria parva sporozoite maturation.
AB  - Adult male and female Rhipicephalus appendiculatus ticks infected with Theileria
      parva (Muguga 3087) were fed on rabbits and the development of infection was
      monitored daily using light microscopy and an in vitro titration technique able
      to quantify the infectivity of sporozoite suspensions. The salivary glands
      stained with methyl green pyronine showed presence of infection in some unfed
      ticks. The intensity of staining was shown to increase with the number of days
      the ticks had fed. The in vitro technique, on the other hand, could detect
      infection only in ticks which had fed for 3-5 days. Feeding of ticks on rabbits
      for 4 days produced significantly more sporozoites than any other lengths of
      feeding (P = 0.001). The in vitro assay was also able to demonstrate differences
      between male and female R. appendiculatus in production of infective sporozoites.
      Female ticks produced significantly more sporozoites than male ticks (P = 0.002).

PMID- 9195715
TI  - How long before resistance makes it impossible to control some field strains of
      Haemonchus contortus in South Africa with any of the modern anthelmintics?
AB  - This paper describes an exceptional spectrum of multiple anthelmintic resistance
      in two strains of Haemonchus contortus in South Africa, one from Howick in
      KwaZulu-Natal, and the other from Badplaas, in Mpumalanga. Apparently for the
      first time, a helminth strain is described with resistance to compounds from all
      five of the modern anthelmintic groups used for nematode control in sheep; also,
      two strains of H. contortus show resistance to the two substituted phenols,
      dinitrophenol and nitroxynil. Only closantel at 5 mg kg-1 of nine compounds
      tested appears to have undiminished efficacy against the Howick strain, but even
      in the case of closantel, the residual activity and minimal effective level need
      to be tested before it can be concluded that its efficiency is unaffected. The
      exceptional resistance of the Howick strain is demonstrated by the fact that
      sequential daily drenching of sheep infected with the strain, with levamisole at
      18 mg kg-1, oxfendazole at 20 mg kg-1, levamisole at 20 mg kg-1 and a mixture of
      fenbendazole at 10 mg kg-1 plus trichlorfon at 132 mg kg-1 on the fourth day,
      failed to clear sheep of the infection. There are strong indications that side
      resistance occurs between dinitrophenol and nitroxynil, on the one hand, and the
      salicylanilides, on the other, and it is suggested that, before long, strains of
      H. contortus will be found with high levels of resistance to all the currently
      available anthelmintics.

PMID- 9195714
TI  - The pathogenic effects of experimental cyathostome infections in ponies.
AB  - Nine pony breed foals were reared indoors, then allocated to one of three groups
      infected with either 3.9 million (Group A) or 3.15 million (Group B) cold
      conditioned third stage cyathostome larvae or kept as uninfected controls (Group
      C). The larvae were administered as a 'trickle' infection of 150000 larvae per
      dose, three times weekly. Blood biochemical and haematological analyses were
      performed weekly and faecal worm egg counts bi-weekly. Complete parasitological
      examinations were performed on all ponies at various times post-initial infection
      (PI): one infected animal at 9 weeks PI, four animals (three infected, one
      control) at 20 weeks PI and four animals (two infected, two controls) at 60-62
      weeks PI. All ponies in the infected groups experienced a marked reduction in
      weight gain and two animals developed clinical disease: one pony developed
      intermittent diarrhoea and colic 8 weeks PI; another pony developed intermittent
      diarrhoea between 30 and 52 weeks PI. All infected ponies had decreased serum
      fructosamine concentrations and five had decreased serum albumin, which were
      first apparent 4-6 weeks PI. Alterations in the composition of serum globulins
      were detected in all ponies. Transient neutrophilia was observed in five animals
      from the infected groups 3-9 weeks PI. Serum alkaline phosphatase concentrations
      were increased in one pony between 30 and 60 weeks PI. During the course of the
      experiment, faecal samples from all infected animals were negative for worm eggs.
      At necropsy, cyathostome larvae were present within the mucosa of the large
      intestine of all infected ponies, however the mucosal larval counts varied
      considerably between individuals.

PMID- 9195716
TI  - Endectocidal efficacies of doramectin in naturally parasitized pigs.
AB  - The studies reported here were conducted to investigate the effectiveness of
      doramectin, given intramuscularly at the rate of 300 micrograms kg-1 of
      bodyweight, in the treatment of naturally acquired porcine nematodosis and
      acariasis. Twenty pigs demonstrated to be naturally infected with pulmonary and
      gastrointestinal nematodes were used in one control study, and 22 pigs
      demonstrated to be naturally parasitized with Sarcoptes scabiei var. suis were
      used in a second study. In both studies, animals were evenly divided between
      doramectin plus vehicle and vehicle-treated groups by restricted randomization.
      In the anthelmintic study, all pigs were necropsied for parasite collection on
      post-treatment Days 14 and 15. The acaricidal evaluation study was 28 days in
      duration after treatment, with mite population quantifications on the day of
      treatment and on post-treatment Days 7, 14, 21 and 28. Doramectin proved 100%
      effective in the removal of Metastrongylus salmi, M. elongatus, M. pudendotectus,
      Strongyloides ransomi, Ascaris suum and Oesophagostomum dentatum. Levels of
      Hyostrongylus rubidus, Ascarops strongylina and Macracanthorhynchus hirudinaceus,
      as observed at necropsy in the doramectin-treated pigs, were reduced by 99.2%,
      99.5% and 62.1%, respectively, as compared with levels seen in the control pigs.
      In regard to Sarcoptes scabiei var. suis, no live mites were recovered from
      doramectin-treated pigs during the 7-28 day post-treatment period. In conclusion,
      doramectin proved highly effective in the treatment of naturally acquired porcine
      nematodosis and Sarcoptes scabiei var. suis infestation. In addition, all
      treatments were safe and well tolerated, with no adverse reactions noted in any
      trial animals.

PMID- 9195717
TI  - The epidemiology of nematode infections in sheep in a cool tropical environment.
AB  - The epidemiology of nematode infections in Menz sheep was studied in the
      highlands of Ethiopia at the International Livestock Research Institute (ILRI),
      Debre Berhan Research Station, using a series of tracer lambs grazing
      contaminated pasture for either 4, 16, 32 or 48 weeks from July 1992 to June
      1994. The basic nematode seasonal infectivity pattern was expressed in terms of
      relative numbers of third-stage larvae (L3) available on pasture for different
      months. Data from faecal nematode egg counts, pasture larval recoveries and worm
      counts from the tracer lambs were used to investigate the infectivity pattern.
      Four nematode species of economic importance: Longistrongylus
      (Pseudomarshallagia) elongata, Trichostronglylus colubriformis, Haemonchus
      contortus, and Dictyocaulus filaria, were recovered from sheep. The largest
      numbers were recovered during the wet season (i.e. July to November) with peaks
      in late August and early September. During this 2 year study period, the seasonal
      pattern of sheep gastrointestinal nematodes was clearly defined. An important
      finding was that conditions during the short rainy season (i.e. March-May) were
      not conducive to the development and survival of nematode eggs and the free
      living stages, hence little or no transmission occurred. Rainfall and humidity
      seemed to be the most important factors for the development of eggs and free
      living stages. The period of acquisition of third-stage larvae from pasture was
      found to be relatively short, suggesting that a strategic control programme is
      feasible with minimal anthelmintic use. Results from the studies are discussed in
      relation to control strategies.

PMID- 9195718
TI  - The influence of a Cooperia oncophora priming on a concurrent challenge with
      Ostertagia ostertagi and C. oncophora in calves.
AB  - The development of immunity to Ostertagia ostertagi and Cooperia oncophora and
      interactions between these species were investigated in experimentally infected
      calves. Parasitological, serological and histological parameters were used for
      assessing immune responses. No conclusive evidence of an effect of C. oncophora
      on the course of an O. ostertagi infection in calves could be shown. Following a
      challenge with C. oncophora and O. ostertagi of C. oncophora primed calves, no
      significant reductions in establishment rate, faecal egg counts, worm length or
      the percentage of early fourth stage larvae could be demonstrated. Results also
      confirmed earlier work showing the very different degrees of immunity conferred
      following immunisation with either C. oncophora or O. ostertagi. While a
      protective immunity was generated in the case of C. oncophora, continuous
      infection of calves with 420000 L3 of O. ostertagi during almost 5 months induced
      immune reactions which affected growth and fecundity of the worms but not the
      establishment rate.

PMID- 9195719
TI  - Evaluation of an ELISA for the routine diagnosis of Dictyocaulus viviparus
      infections in cattle.
AB  - An enzyme-linked immunosorbent assay (ELISA) that detects antibodies against
      Dictyocaulus viviparus in experimentally and naturally infected cattle was
      evaluated for its sensitivity, specificity, the moment of seroconversion and
      persistence of the anti-D. viviparus response and precision. The first three
      parameters were compared with those of an indirect haemagglutination assay (IHA).
      Specificity and sensitivity of both assays were assessed in sera collected from
      calves experimentally infected with pure isolates of D. viviparus, Ostertagia
      ostertagi, Cooperia oncophora, Nematodirus helvetianus, Ascaris suum or Fasciola
      hepatica, and from parasite-naive calves. The specificity of both the ELISA and
      IHA was very high, 99.2% and 99.6%, respectively. The sensitivity of the ELISA
      (100%) was significantly higher than that of the IHA (78.1%). In experimentally
      infected cattle, D. viviparus-specific antibodies were first detected with the
      ELISA between days 28 and 42 post-infection (p.i.), whereas the IHA only became
      positive between days 42 and 70. With the ELISA, antibody levels persisted until
      day 168 p.i. The IHA remained positive until the end of the experiment (day 196).
      None of the vaccinated animals were seropositive with the ELISA, whereas 25% of
      the calves were seropositive with the IHA. The seroprevalence of D. viviparus
      infections was determined in a field study with 467 sera from cattle of 64 herds;
      227 (48.6%) of the animals were seropositive with the ELISA whereas only 38
      (8.1%) scored positive with the IHA. To determine the precision of the ELISA, a
      total of five laboratories participated in trials, in which panels of strong
      positive, positive, and weak positive candidate sera were tested blind according
      to an international (International Standard ISO 5725, 1986) standard procedure.
      The repeatability and reproducibility of the ELISA were 0-16% and 14-26%,
      respectively. After these promising results it was decided to introduce this
      ELISA in 1995 as a routine test in all Animal Health Services in the Netherlands,
      replacing the IHA and faecal examinations for lungworm.

PMID- 9195720
TI  - Controlled dose confirmation study of a 2% moxidectin equine gel against equine
      internal parasites in The Netherlands.
AB  - The efficacy of a 2% moxidectin equine gel at a dosage rate of 0.4 mg kg-1 was
      evaluated in a controlled trial at Utrecht University. Twelve yearling castrated
      male Shetland ponies grazed a pasture of 2 ha from May 1994 until housing in
      November. Six ponies were treated with moxidectin, whereas the others served as
      non-treated controls. Necropsy was carried out 35 days after treatment. Greater
      than 99% efficacy of moxidectin was observed on faecal egg output. No effect of
      moxidectin was observed on mucosal inhibited early cyathostome L3 (EL3) or on the
      total numbers of mucosal developing stages. However, a 89.6% reduction was
      observed on large mucosal fourth stage larvae (L4). Moxidectin treatment probably
      triggered resumption of development of EL3. Moxidectin appeared to be highly
      effective (95-100%) on lumenal L4 cyathostomes, adult strongylids, Strongylus
      vulgaris larvae from the arteries, S. edentatus larvae from the abdominal wall
      and Trichostrongylus axei. Moxidectin had relatively poor efficacy against
      Gasterophilus intestinalis and had no effect on Anoplocephala perfoliata. No side
      effects of moxidectin treatment were observed.

PMID- 9195721
TI  - Seasonal changes in the level of infective strongylate nematode larvae on pasture
      in the coastal savanna regions of Ghana.
AB  - The level and type of infective strongylate nematode larvae on pasture were
      followed from March 1994 to April 1995 in the coastal savanna regions of Ghana.
      The number of infective larvae on pasture was high, reaching 2458 kg-1 dry matter
      of grass during the period of and soon after the rains, and very low or none in
      the absence of rainfall. The number of infective larvae on pasture was directly
      related to the pattern of rainfall, but it was also influenced by the number of
      raindays in the period. The following genera were found in order of prevalence:
      Haemonchus, Oesophagostomum, Trichostrongylus, Cooperia. The mean total adult
      worm burdens of tracer lambs released monthly were related to the levels of
      herbage infective larvae.

PMID- 9195723
TI  - Using slaughter inspections to evaluate sarcoptic mange infestation of finishing
      swine.
AB  - Sarcoptic mange is one of the common swine diseases worldwide. Although mange
      free populations can be established with caesarean derived stock, by herd
      repopulation programmes or by eliminating mange with ivermectin, mange remains
      prevalent in many countries. Field and experimental studies indicate that
      hypersensitive mange is detrimental to performance of growing pigs. Typically,
      producers tolerate mange infestation in their herds and control measures are
      often haphazard. This tolerance to mange infestation is attributable to the
      covert nature of the losses (reduced growth rate and feed efficiency without
      mortality) and to the fact that clinical signs of hypersensitive mange (pruritus)
      are usually viewed as normal. Lack of tools to evaluate mange severity in pigs
      and to demonstrate its importance has hindered the efforts of veterinarians to
      control the disease. Traditionally, veterinarians have used slaughter inspections
      to assess respiratory diseases such as enzootic pneumonia and atrophic rhinitis.
      Much of the value of slaughter inspections is as a tool with which veterinarians
      can educate and motivate their clients to improve disease control measures. The
      potential for evaluating hypersensitive mange by inspecting slaughtered pigs for
      lesions of papular dermatitis was recognised some time ago, but quantitative
      evaluation of the reliability of this approach has been lacking. We have
      conducted several studies in Australia, the USA, Canada, Europe and Latin America
      to evaluate associations between Sarcoptes infestation and the severity of
      papular dermatitis at slaughter, using a simple ordinal scale for classifying
      carcasses. Our initial field and experimental data in Australia indicated the
      specificity of localised dermatitis to be in the order of 75-80%, but that the
      generalised dermatitis was highly specific (> 98%) for mange. Subsequent studies
      in the US Midwest yielded almost identical results, and indicated that the method
      may also have some utility for surveillance of mange-free herds. Results from
      other locations invariably have shown significant associations between dermatitis
      lesions and mange infestation. Relative to other methods such as skin scrapings
      and monitoring pruritus, this method is simple and relatively objective, and
      should be considered for routine inclusion in slaughter inspection protocols.

PMID- 9195722
TI  - Attempted transmission of human granulocytotropic Ehrlichia (HGE) by Amblyomma
      americanum and Amblyomma maculatum.
AB  - Transstadial transmission of human granulocytotrophic Ehrlichia (HGE) was
      attempted in dogs using Amblyomma americanum (L.) and A. maculatum Koch, two
      species that, as adults, feed readily on human beings. Larvae and nymphs were
      acquisition-fed on a dog that was parasitemic with HGE. Two months later,
      following digestion of the blood meal and subsequent molting to nymphal or adult
      stage, these ticks were fed to repletion on HGE-naive dogs. None of the dogs
      developed clinical evidence of ehrlichiosis. Parasites were not observed in blood
      smears by light microscopy, HGE DNA was not detected by polymerase chain
      reaction, and none of the dogs seroconverted. Based on this trial, we conclude
      that, unlike E. chaffeensis, HGE is probably not transmitted from dog to dog by
      either A. americanum or A. maculatum.

PMID- 9195724
TI  - Hepatozoon canis infection in a litter of Dalmatian dogs.
AB  - Infection with Hepatozoon canis is described in a litter of seven Dalmatians.
      Four littermates were presented with concurrent hepatozoonosis and parvoviral
      enteritis and the remaining three puppies were parasitemic with H. canis with no
      other concurrent disease. Parasitemia ranged between 3% and 67% of the blood
      neutrophils. The mean number of parasitized neutrophils per microliter among
      littermates with concurrent hepatozoonosis and parvoviral enteritis was 1139 (+/
      447 SD) on the day of admission, compared with 470 (+/-379) among littermates
      with hepatozoonosis only. Puppies with hepatozoonosis and parvovirus infection at
      admission differed significantly in their degree of H. canis parasitemia from
      their littermates which were not infected with parvovirus (P = 0.0286).
      Concurrent parvoviral enteritis and hepatozoonosis in the dog are reported here
      for the first time.

PMID- 9195725
TI  - Experimental cryptosporidiosis in adult and neonatal rabbits.
AB  - Neonatal and adult New Zealand White rabbits were infected experimentally with
      Cryptosporidium parvum. No histologic evidence of infection was found in adult
      rabbits. However, increased levels of anti-cryptosporidial serum IgG were
      present, and multiple antigens were detected by serum on immunoblots. In
      neonates, variably severe, transient infection was present from Days 3 to 21
      postinoculation. Serum IgG was initially elevated, decreased until Day 10
      postinoculation, then progressively increased for the remainder of the study. A
      prominent 15 kilodalton antigen was detected on immunoblots using serum obtained
      on Days 14 until 28 postinoculation. Neonate anti-cryptosporidial fecal IgA were
      slightly elevated on Days 14 and 21 postinoculation.

PMID- 9195726
TI  - Serodiagnosis of Babesia equi infection--a comparison of Dot-ELISA, complement
      fixation test and capillary tube agglutination test.
AB  - The present study aimed to develop Dot-ELISA, complement fixation test (CFT) and
      capillary tube agglutination test (CAT) for serodiagnosis of Babesia equi
      infection and to compare their sensitivity with each other. For this study,
      sequential serum samples were collected from four donkeys experimentally infected
      with B. equi up to 90 days post infection (P.I.). B. equi antigen was prepared
      from the blood of a donkey showing more than 80% parasitaemia. Dot-ELISA, CF and
      CA tests were standardized as per the standard method. While performing CFT, it
      was observed that CFT standardized for the donkey system could not be applied to
      the horse system, and different units of the same antigen and complement were
      required for each. Dot-ELISA detected antibodies from 3-6 days P.I. onwards,
      whereas CF and CA tests could detect antibodies from the 6th day P.I. indicating
      that Dot-ELISA is the more sensitive. The efficacy of these three tests was also
      determined by testing 211 field serum samples of apparently healthy horses. By
      Dot-ELISA 49.76%, by CAT 42.18% and by CFT 27.86% of the serum samples were found
      positive. As the results of Dot-ELISA and CAT are comparable, it is proposed that
      CAT may be used as a screening test.

PMID- 9195727
TI  - Morphological changes in the jejunum of calves naturally infected with Giardia
      spp. and Cryptosporidium spp.
AB  - Giardiosis and cryptosporidiosis are frequently diagnosed in calves at the large
      animal clinic of the veterinary school. Few studies have been reported in the
      literature regarding pathogenesis of these two intestinal protozoa. The aims of
      this study were to follow the histological changes in the villi and crypts and
      the changes in the number of intraepithelial lymphocytes in the jejunum of
      naturally infected calves during the acute phase of infection. For this purpose,
      29 calves aged between 7 and 10 days were bought at a local auction. The animals
      were housed in individual pens to avoid cross-contamination. Fecal samples were
      examined microscopically for the presence of Giardia cysts and Cryptosporidium
      oocysts, three times per week for a period of 45 days. Six calves did not pass
      any cysts or oocysts and were used as controls. Fifteen calves passed Giardia
      cysts only, five passed both cysts and oocysts, and three passed oocysts only.
      The villus to crypt ratio index was 1.76 in the control group and 1.08 in the
      Giardia-infected group. In the Cryptosporidium-infected calves, the ratio was
      1.18 and calves infected with both parasites had an index of 1.37. The number of
      intraepithelial lymphocytes per millimeter of jejunum tissue was 21 in the
      control group. This number was doubled in the calves infected with Giardia, but
      was slightly lower in the other infected groups. All of the infected calves had
      intermittent diarrhea and mucus was seen in many fecal samples.

PMID- 9195728
TI  - Increased resistance to Anaplasma marginale infection in cattle chronically
      infected with Theileria buffeli (syn. T. orientalis).
AB  - Calves chronically infected with the benign haemoprotozoan parasite Theileria
      buffeli (syn. T. orientalis) and T. buffeli-free calves were experimentally
      infected with virulent Anaplasma marginale. The daily mean maximum parasitaemia
      in the T. buffeli-carrier calves was lower and delayed relative to that of the
      Theileria-free calves. Anaemia was less marked in the Theileria infected calves,
      although this difference was not statistically significant. The susceptibility of
      Theileria-carrier and Theileria-free older cattle to virulent A. marginale
      infection was also investigated. The mean maximum parasitaemia observed in the
      Theileria-infected cattle was significantly lower than that of the Theileria-free
      cattle and the time to maximum parasitaemia was increased significantly in the
      Theileria-infected relative to the Theileria-free cattle. Of the Theileria
      carrier cattle, 33% exhibited maximum parasitaemias of less than 0.1% infected
      erythrocytes and no clinical anaemia as a result of A. marginale infection. In
      contrast, the lowest maximum parasitaemia observed in the Theileria-free cattle
      was 7%. The percentage of cattle requiring treatment to prevent mortality due to
      anaemia was 50% and 91% in the Theileria-infected and Theileria-free cattle
      respectively. For the duration of increasing A. marginale parasitaemia, the level
      of Theileria in carrier cattle was significantly depressed or undetectable.
      Following the resolution of peak A. marginale parasitaemia, the level of
      Theileria parasites increased rapidly to become significantly higher than that
      prior to infection and then decreased gradually to a level similar to that prior
      to infection. The mechanism of the increased resistance to A. marginale infection
      conferred by T. buffeli-carrier state is unknown, but is likely to involve non
      specific cell-mediated immunity, as no serological cross-reactivity exists
      between these two highly divergent parasite species. The susceptibility of
      relatively mature cattle to clinical anaplasmosis under field conditions is
      likely to be significantly affected by the widespread distribution and common
      occurrence of T. buffeli throughout the range of A. marginale in Australia,
      Africa and southeast Asia.

PMID- 9195729
TI  - Acquired protection of the rabbit (Oryctolagus cuniculus) against coccidiosis
      using a precocious line of Eimeria magna: effect of vaccine dose and age at
      vaccination.
AB  - Sucklings were vaccinated orally once at 25, 27 or 29 days of age with a
      precocious line of Eimeria magna. Each group received two doses varying from 3.5
      x 10(2) to 3.5 x 10(4) oocysts. At 36 days of age, animals received a challenge
      inoculation with 10(4) oocysts of the wild strain of E.magna. Vaccination reduced
      oocyst output 10 to 1000 times after the challenge inoculation and prevented the
      decrease in the weight gain observed in non vaccinated challenged animals. When
      the vaccination was performed more than 9 days before challenge, full protection
      was obtained. An individual oral vaccination performed with 3500 oocysts gave
      total protection whatever the age at vaccination between 25 and 29 days of age.

PMID- 9195730
TI  - Experimental toxoplasmosis in broiler chicks.
AB  - To evaluate chicken toxoplasmosis both as an economic and a public health
      subject, 84 broiler chicks of a commercial strain, 30 days old, were distributed
      into seven groups of 12 birds (three replications of four chicks) experimentally
      infected with three developing T. gondii stages of the P strain as follows:
      tachyzoites, intravenous (two groups: 5.0 x 10(5) and 5.0 x 10(6)), cysts, per os
      (two groups: 1.0 x 10(2) and 1.0 x 10(3)) and oocysts, per os (three groups: 5.0
      x 10(2), 5.0 x 10(3) and 5.0 x 10(4)). Twelve chicks received only a placebo
      (control group). During the next 30 days the following parameters were estimated:
      productivity (weight gain and feed conversion), clinical signs, including rectal
      temperature and parasitemia (bioassay). No clinical signs suggesting
      toxoplasmosis were seen and no statistical differences on productivity standards
      were found in comparison between inoculated and control chicks. However, fowls
      inoculated with tachyzoites and oocysts occasionally showed hyperthermia. Some
      haematological changes were detected in fowls inoculated with T. gondii. Anatomo
      histopathological changes were not observed. From 14 parasitemias detected, 35.7%
      appeared on the 5th day after inoculation and 57.1% of them resulted from oocysts
      inoculation. After 30-35 days all birds were slaughtered: fragments from 12
      organs or tissues from each of them were subjected to artificial peptic digestion
      and after that injected into T. gondii antibody-free mice (IIFR). T. gondii was
      detected in brain (12), pancreas (five), spleen (five), retina (five), kidney
      (two), heart (four), proventriculus (three), liver (two), intestine (two), lung
      (one), and skeletal muscle (one). Similar to observations with parasitemia, from
      42 T. gondii isolations, 59.5% came from chicks which had received oocysts. It
      can thus be inferred that the developing form, expelled by cats, is the most
      important for T. gondii chicken infection and that brain is the most infected
      organ in birds. Attention must be paid to the potential importance of chicken
      meat in public health, since T. gondii was isolated from skeletal and heart
      muscles.

PMID- 9195731
TI  - The survival and transmission of oocysts of Eimeria alabamensis in hay.
AB  - From a permanent pasture where young cattle had contracted coccidiosis due to
      Eimeria alabamensis 2 years previously, hay was harvested and fed to six 2-4
      month old calves 15 days, 4 months or 8 months after being harvested. The
      excretion of oocysts by these exposed calves was compared with that by five
      control calves of similar age which were housed in the same premises but fed hay
      from a 'coccidia-free' field. All calves fed the contaminated hay developed
      patent E. alabamensis infections and excreted 142000 to 4.2 million oocysts of
      this species per gram of faeces starting 8 days after the hay was first fed. Five
      of them had soft (porridge-like to gruel-like) faeces and/or poor appetite. The
      control calves excreted no or very few oocysts and had firm faeces and unaffected
      appetite. It is concluded that making hay from pastures contaminated with oocysts
      of E. alabamensis is unsatisfactory if the hay is to be used for feeding young
      cattle.

PMID- 9195732
TI  - Fasciola hepatica: vaccination of rabbits with native and recombinant antigens
      related to fatty acid binding proteins.
AB  - The current study was designed to compare the immunogenic and immunoprophylactic
      properties of native (nFh12) and recombinant (rFh15) antigens from Fasciola
      hepatica in rabbits infected with the fluke. Levels of specific anti-nFh12 and
      anti-rFh15 antibodies were significantly higher in the rabbits vaccinated twice
      compared with non-vaccinated infection controls. A reduction of 40% in worm
      burdens was found in rabbits immunized with nFh12 and infected 4 weeks after the
      second immunization. The recombinant vaccine induced lesser levels of protection
      than the native one, suggesting that both molecules may have slight differences
      either in immunogenicity or in their configuration. Further biochemical studies
      are required to define these differences. The mean length of flukes recovered was
      always smaller in all vaccinated rabbits. In addition, infected control rabbits
      had higher gamma glutamil transferase (GGT) levels than immunized rabbits.
      Lastly, gross anatomic observation always showed fewer liver lesions in all
      vaccinated rabbits than in controls. This finding clearly supports the
      possibility of vaccination regimes in fasciolosis.

PMID- 9195733
TI  - The use of monoclonal antibody for the immunodiagnosis of Fasciola gigantica
      infection in cattle.
AB  - Antigens that were specific to Fasciola gigantica were obtained from the whole
      worm homogenate of the parasite by immunoaffinity chromatography in cyanogen
      bromide-activated sepharose 4B columns and used for the production of monoclonal
      antibodies. The F. gigantica-specific monoclonal antibody was labelled with
      horseradish peroxidase and used for the detection of circulating antigen by the
      direct ELISA method in the sera of cattle experimentally infected with the
      parasite. Circulating antigens were detectable in the sera of the animals as from
      the third week after infection while negative absorbance values were obtained 2
      weeks after the termination of the infection by chemotherapy with oxyclozanide.
      This immunodiagnostic method offers an attractive alternative as a supplement to
      the conventional coprological diagnosis of fasciolosis.

PMID- 9195735
TI  - Pathophysiological aspects of Mecistocirrus digitatus (Nematoda:
      Trichostrongylidae) infection in calves.
AB  - Three groups of four calves were experimentally infected with infectious larvae
      of Mecistocirrus digitatus. One group received a trickle infection of 5000 L3 per
      day for 8 days, the other two groups received a single infection of 5000 and
      40,000 L3, respectively. All animals were necropsied 120 days after infection.
      Prepatent periods varied between 61 and 79 days, and maximal faecal egg output
      was reached between 80 and 100 days after infection. Repeated infections were not
      additive and worm counts at 120 days after infection varied between 100 and 440
      in the first two groups and between 120 and 1700 in the last group. There was no
      significant difference in worm counts between the different infection regimes.
      However, there was a significant positive relationship between worm burden and
      faecal egg counts. In addition, there were significant negative relationships
      between worm burden and packed cell volume, and weight gain. The relative
      decreases in packed cell volume and weight gain emerged 70-80 days after
      infection. Serum pepsinogen levels were significantly elevated by the end of the
      trial, but the observed positive relationship between worm burden and pepsinogen
      was not significant. An enzyme immunoassay based on crude adult antigen was able
      to detect M. digitatus infection at 90 and 100 days after infection, but again
      there was no significant association between worm burden and antibody levels.
      Therefore, anaemia and a reduction in weight gain caused by the haematophagous
      activity of adult stages seem to be the most important pathogenic effects of M.
      digitatus infection in calves.

PMID- 9195734
TI  - Modified plasma and abomasal disposition of albendazole in nematode-infected
      sheep.
AB  - The influence of gastrointestinal nematode infection on the kinetics of
      albendazole (ABZ) and its metabolites, albendazole sulphoxide (ABZSO) and
      sulphone (ABZSO2) in plasma and abomasal fluid was investigated in sheep. A
      micronised suspension of ABZ was administered intraruminally at 7.5 mg kg-1 to
      the following groups of sheep: (a) non-parasitised (control); (b) artificially
      infected with Haemonchus contortus; (c) naturally infected with Haemonchus
      contortus and other species of gastrointestinal nematodes. Plasma and abomasal
      fluid samples were obtained serially over 72 h post-treatment and they were
      analysed by HPLC for ABZ and its metabolites. The ABZ parent drug was not
      detected in plasma at any time post-treatment, however the metabolites ABZSO and
      ABZSO2 were recovered in the bloodstream. The active metabolite ABZSO was
      recovered in plasma between 0.5 and 48 (uninfected), 60 (H. contortus infected)
      or 72 h (naturally infected sheep) post-administration. The area under the plasma
      concentration vs time curve (AUC) values for ABZSO were higher in both
      artificially infected (64.0 micrograms h ml-1) and naturally infected (79.3
      micrograms h ml-1) sheep as compared with non-infected animals (41.8 micrograms h
      ml-1). Peak plasma concentrations for ABZSO and ABZSO2 were higher in both
      artificially and naturally infected sheep than in non-parasitised animals. No
      changes in the half-lives and mean residence times for these metabolites were
      observed in infected sheep. ABZ and its metabolites were found in the abomasum
      between 0.5 and 48 (infected animals) or 72 h (uninfected) post-treatment. The
      availability (total AUCs) of ABZ and its metabolites in abomasal fluid were lower
      in H. contortus infected sheep than in the uninfected control animals. The
      increased abomasal pH induced by the presence of the H. contortus infection may
      reduce the plasma/abomasum pH gradient, which results in a decreased ionic
      trapping of ABZ and its metabolites in the abomasum. Such a phenomenon correlates
      with: (a) the higher total AUC values obtained for ABZ metabolites in the
      bloodstream of the infected compared to the control sheep, (b) the lower
      concentration profiles of the ABZ parent drug and its metabolites found in the
      abomasal fluid of the infected animals.

PMID- 9195736
TI  - Resistance of four sheep breeds to natural and subsequent artificial Haemonchus
      contortus infection.
AB  - The response of Red Maasai sheep to natural and artificial Haemonchus contortus
      infections was compared with sheep of Blackheaded Somali, Dorper and Romney Marsh
      breeds. Significant breed differences in egg count, packed cell volume (PCV), and
      mortality rates showed that the Red Maasai sheep were more resistant to natural
      H. contortus infection than sheep from the other three breeds. Of the initial
      groups of 15 wethers of each breed, two animals from each of the Dorper and
      Blackheaded Somali groups and nine from the Romney Marsh group died with
      haemonchosis during a 12 month field study. Following artificial infection of the
      Red Maasai, Dorpers and Blackheaded Somalis, with 10000 H. contortus L3, the Red
      Maasai sheep maintained a lower egg output and a higher PCV than animals of the
      other two breeds. The results clearly showed that breed substitution with the Red
      Maasai is a control option in areas where sheep are kept for meat and H.
      contortus is endemic.

PMID- 9195737
TI  - Response to artificial and subsequent natural infection with Haemonchus contortus
      in red Maasai and Dorper ewes.
AB  - Maiden Red Maasai and Dorper ewes were kept indoors and artificially infected
      with a single oral dose of 5000 infective larvae of Haemonchus contortus. Their
      faecal egg counts (FEC) and packed red cell volumes (PCV) were monitored for 9
      weeks. They were then treated with an anthelmintic and turned out to graze
      together on a pasture contaminated with H. contortus. They grazed this pasture
      for 14 months and were allowed to mate and lamb. While at pasture the ewes were
      monitored for FEC, PCV and peripheral eosinophilia. Red Maasai ewes had
      significantly lower FEC, and for certain periods, significantly higher PCV and
      peripheral eosinophilia. During the periparturient period, FEC were about twice
      as high in the Dorper breed as the Red Maasai. These results confirm and extend
      previous reports on the superiority of the Red Maasai breed in East Africa.

PMID- 9195738
TI  - Density and distribution of cattle lice (Phthiraptera:Haematopinidae,
      Linognathidae, Trichodectidae) on six steers.
AB  - The density and distribution of four species of cattle louse, Bovicola bovis
      (L.). Haematopinus eurysternus (Nitzsch), Linognathus vituli (L.), and
      Solenopotes capillatus (Enderlein), were elucidated from the hides of six
      slaughtered steers. Adult and nymphal lice were first removed from one hide by
      hand and the location of each specimen mapped. The remaining lice were removed by
      a detergent wash, and KOH dissolution of hide and hair. Lice from the remaining
      five hides were removed using KOH dissolution of cattle hair and subsequent
      filtration of the effluent. Bovicola bovis was most abundant, followed by H.
      eurysternus, L. vituli and S. capillatus. Significant variation was observed in
      B. bovis, H. eurysternus and L. vituli population densities. Solenopotes
      capillatus population densities did not differ significantly. All species were
      contagiously distributed, i.e. 'clumped', suggesting species dependent
      predilection sites. Predilection sites were ranked according to louse density to
      facilitate the development of field sampling strategies. Additional biological
      data were gathered on sex and life stage ratios for each species.

PMID- 9195740
TI  - Characterization of the subclinical phase of canine ehrlichiosis in
      experimentally infected beagle dogs.
AB  - Beagle dogs were examined during the subclinical phase of canine ehrlichiosis
      under controlled conditions. Emphasis was placed on gathering data before
      artificial inoculation with Ehrlichia canis, and comparing these data with those
      of the subclinical phase of the disease. In this study all dogs were clinically
      healthy throughout the 6 month examination period. All subclinically infected
      dogs had IFA antibody titers to E. canis at a dilution varying from 1:2560 to
      1:20480. The most prominent haematological finding was mild thrombocytopenia with
      a concomitant increase in platelet size, seen in eight of the nine dogs examined.
      Leukocyte counts were statistically significantly reduced in 78% of the dogs,
      compared with their preinfection values, with 71% of dogs having significantly
      reduced absolute neutrophil counts. None of the dogs were either leukopenic nor
      neutropenic. Six of the nine dogs had increased serum gamma-globulin
      concentrations. No dogs were overtly anemic, although declines in packed cell
      volume, haemoglobin concentration and total erythrocyte count were detected in an
      inconsistent manner among the dogs. It was concluded that, the most reliable
      parameters for judging possible subclinical ehrlichial infection in beagle dogs
      was mild thrombocytopenia, together with a persistently high antibody titer to E.
      canis. Hypergammaglobulinemia would increase the suspicion further. Based on the
      results presented, routine testing of dogs in E. canis endemic areas is
      recommended in order to identify and treat dogs in the subclinical phase of the
      disease.

PMID- 9195739
TI  - Monoclonal antibodies against Boophilus microplus and their effects on tick
      reproductive efficiency.
AB  - Four monoclonal antibodies (mAbs) against extracts of embryo and gut tissue
      obtained from fully engorged Boophilus microplus were produced. The mAb BrBml
      reacted with different instars and tissues, the BrBm2 recognized only antigens
      present in gut extract and the mAbs BrBm3 and BrBm4 recognized vitellin. The
      effect of inoculation of these mAbs into fully engorged Boophilus microplus
      females was also evaluated. The mAbs BrBm1 and BrBm2 caused a decrease in
      oviposition of approximately 50% and 70%, respectively, and the mAbs BrBm3 and
      BrBm4 did not affect reproductive efficiency. This assay may be useful as a low
      cost test to provide preliminary information on the possible effects of anti-tick
      antibodies in damaging ticks before attempting cattle vaccination experiments.

PMID- 9195742
TI  - On the correlation dimension of optokinetic nystagmus eye movements:
      computational parameters, filtering, nonstationarity, and surrogate data.
AB  - We discuss the estimation of the correlation dimension of optokinetic nystagmus
      (OKN), a type of reflexive eye movement. Parameters of the time-delay
      reconstruction of the attractor are investigated, including the number of data
      points, the time delay, the window duration, and the duration of the signal being
      analyzed. Adequate values are recommended. Digital low-pass filtering causes the
      dimension to increase as the filter cutoff frequency decreases, in accord with a
      previously published prediction. The stationarity of the correlation dimension is
      examined; the dimension appears to decrease over the course of 120 s of
      continuous stimulation. Implications for the reliable estimation of the dimension
      are considered. Several surrogate data sets are constructed, based on both early
      (0-30 s) and late (100-130 s) OKN segments. Most of the surrogate data sets
      randomize some aspect of the original OKN, while maintaining other aspects.
      Dimensions are found for all surrogates and for the original OKN. Evidence is
      found that is consistent with some amount of deterministic and nonlinear dynamics
      in OKN. When this structure is randomized in the surrogate, the dimension changes
      or the dimension algorithm ceases to converge to a finite value. Implications for
      further analysis and modeling of OKN are discussed.

PMID- 9195741
TI  - Efficacy of pour-on and injectable formulations of moxidectin and ivermectin in
      cattle naturally infected with Psoroptes ovis: parasitological, clinical and
      serological data.
AB  - On the basis of Psoroptes ovis counts performed on day -7, 32 animals were
      randomly allocated to a control group of five animals or to four groups
      comprising six or seven animals which were treated, respectively, with pour-on
      ivermectin (IPO), injectable ivermectin (II), pour-on moxidectin (MPO) and
      injectable moxidectin (IM). Living mites were counted in skin scrapings on days
      0, 7, 14, 28, 42 and 56 post-treatment (PT). Lesions were recorded on a
      standardized map on days 0 and 56 PT. Antibody kinetics were studied using ELISA
      on serially diluted sera. The antibody titres were expressed as the dilution
      giving the positive/negative cut-off. Until their treatment on day 28, the
      control animals remained parasitologically positive and their antibody titres
      increased. In treated groups, all living mite counts were negative on days 28 and
      42 PT but some animals were still infected on days 7 and 14 PT. On day 56, living
      P. ovis were found in one animal of the IPO group. An equation of regression
      describing the antibody decrease was calculated with each individual data set. In
      most of the treated animals, the coefficient of determination R2, which describes
      the closeness of fit to the linear model, was above 0.9. The linear model could
      not be applied (low R2) to the antibody kinetics of four animals: the day 56
      positive animal and its two neighbours in the IPO group and one animal from the
      MPO group. In the treated groups, the differences between the numbers of infected
      animals, the mean daily weight gains or the mean antibody titres were not
      statistically significant. Mean daily weight gains of the treated groups were
      higher than in control animals.

PMID- 9195743
TI  - Self-organization of trajectory formation. I. Experimental evidence.
AB  - Most studies examining the stability and change of patterns in biological
      coordination have focused on identifying generic bifurcation mechanisms in an
      already active set of components (see Kelso 1994). A less well understood
      phenomenon is the process by which previously quiescent degrees of freedom (df)
      are spontaneously recruited and active df suppressed. To examine such behavior,
      in part I we study a single limb system composed of three joints (wrist, elbow,
      and shoulder) performing the kinematically redundant task of tracing a sequence
      of two-dimensional arcs of monotonically varying curvature, kappa. Arcs were
      displayed on a computer screen in a decreasing and increasing kappa sequence, and
      subjects rhythmically traced the arcs with the right hand in the sagittal plane
      at a fixed frequency (1.0 Hz), with motion restricted to flexion-extension of the
      wrist, elbow, and shoulder. Only a few coordinative patterns among the three
      joints were stably produced, e.g., in-phase (flexion-extension of one joint
      coordinated with flexion-extension of another joint) and antiphase (flexion
      extension coordinated with extension-flexion). As kappa was systematically
      increased and decreased, switching between relative phase patterns was observed
      around critical curvature values, kappa c. A serendipitous finding was a strong
      2:1 frequency ratio between the shoulder and elbow that occurred across all
      curvature values for some subjects, regardless of the wrist-elbow relative phase
      pattern. Transitions from 1:1 to 2:1 frequency entrainment and vice versa were
      also observed. The results indicate that both amplitude modulation and relative
      phase change are utilized to stabilize the end-effector trajectory. In part II, a
      theoretical model is derived from three coupled nonlinear oscillators, in which
      the relative phases (phi) between the components and the relative joint
      amplitudes (rho) are treated as collective variables with arc curvature as a
      control parameter.

PMID- 9195744
TI  - Self-organization of trajectory formation. II. Theoretical model.
AB  - Most studies of movement coordination deal with temporal patterns of
      synchronization between components, often without regard to the actual amplitudes
      the components make. When such a system is required to produce a composite action
      that is spatially constrained, coordination persists, but its stability is
      modulated by spatial requirements effected, we hypothesize, through the component
      amplitudes. As shown experimentally in part I, when a redundant three-joint
      system (wrist, elbow, and shoulder) is required to trace a specified arc in
      space, the joint angles may be frequency- and phased-locked even as the curvature
      of the trajectory is manipulated. Transitions between joint coordination patterns
      occur at a critical curvature, accompanied by a significant reduction in wrist
      amplitude. Such amplitude reduction is viewed as destabilizing the existing
      coordinative pattern under current task constraints, thereby forcing the joints
      into a more stable phase relationship. This paper presents a theoretical analysis
      of these multijoint patterns and proposes an amplitude mechanism for the
      transition process. Our model uses three linearly coupled, nonlinear oscillators
      for the joint angles and reproduces both the observed interjoint coordination and
      component amplitude effects as well as the resulting trajectories of the end
      effector.

PMID- 9195745
TI  - Study of human forearm posture maintenance with a physiologically based robotic
      arm and spinal level neural controller.
AB  - The goals of this research are: (1) to apply knowledge of human neuro-musculo
      skeletal motion control to a biomechanically designed, neural controlled,
      'anthroform' robotic arm system, (2) to demonstrate that such a system is capable
      of responses that match those of the human arm reasonably well in comparable
      experiments, and (3) to utilize the anthroform arm system to study some
      controversial issues and to predict new phenomena of the human motion control
      system. A physiologically analogous artificial neural network controller and an
      anatomically accurate robotic testing elbow are applied in this study. In order
      to build the physical elbow system to have mechanical properties as close as
      possible to the human arm, McKibben pneumatic artificial muscles, force sensors,
      and mechanical muscle spindles are integrated in the system with anatomically
      accurate muscle attachment points. A physiologically analogous, artificial neural
      network controller is used to emulate the behavior of spinal segmental reflex
      circuitry including Ia and Ib afferent feedbacks. Systematic experiments of elbow
      posture maintenance are performed and compared with physiological experimental
      data. New experiments are performed in which responses to torque perturbation are
      measured when selected afferent pathways are blocked. A 'covariance diagram' is
      introduced. And a linear model is used to help to analyze the roles of system
      components. The results show that muscle co-contraction and Ia afference with
      gamma dynamic motoneuron excitation are two efficient ways to increase joint
      stiffness and damping, which in turn reduces the mechanical sensitivity of the
      joint to external perturbation and shortens the settling time of the system.

PMID- 9195746
TI  - Dynamic detection of rhythmic oscillations in heart-rate tracings: a state-space
      approach based on fourth-order cumulants.
AB  - This paper presents a new procedure specifically aimed at providing a dynamical
      detection of the oscillations occurring in long-term heart-rate (HR) tracings.
      The procedure is based on a time-variant state-space modelling of the fourth
      order cumulants of the HR signal. The state-space estimator was selected because
      of its demonstrated capability to distinguish between deterministic and
      stochastic components of the signal, while the fourth-order cumulants of the
      signal were used as input of the model to further reduce adverse effects of
      coloured, white and l/f Gaussian noise possibly present in the input data. The
      procedure was tested by the analysis of simulated signals and its performance was
      compared with the results obtained by state-space modelling applied directly on
      the test signals (instead of on the fourth-order cumulants of the signals) and by
      the more traditional auto-regressive modelling. The comparison has shown a clear
      superiority of the proposed procedure over the other techniques in discriminating
      deterministic oscillations from coloured noise. Finally, the applicability of the
      procedure to biological data was verified by analysing five experimental HR
      tracings recorded in normal subjects during laboratory and daily life conditions.

PMID- 9195747
TI  - Action potentials and ionic currents through paranodally demyelinated human motor
      nerve fibres: computer simulations.
AB  - The relationship between the changes in the passive paranodal properties of the
      myelinated human motor nerve fibres and the conduction abnormalities obtained is
      examined on the basis of a double-cable model. Simulated systematic demyelination
      (all paranodal regions uniformly affected) and focal demyelination (paranodal
      regions at each end of a single internode affected) of the fibres are defined as
      a reduction of the paranodal seal resistance. By increasing the degree of
      demyelination, the kinetics of the action potentials and ionic currents in
      different segments of the fibres are explored. The altered paranodal seal
      resistance is found to be a factor impeding the invasion of the demyelinated
      regions by an action potential. We established that the conduction along the most
      severely demyelinated fibres (i.e. in the case of systematically demyelinated
      fibres) is more affected than along the focally demyelinated fibres.

PMID- 9195749
TI  - Three-dimensional reconstruction of aqueous channels in human trabecular meshwork
      using light microscopy and confocal microscopy.
AB  - Conventional two-dimensional imaging of the trabecular meshwork (TM) provides
      limited information about the size, shape, and interconnection of the aqueous
      channels within the meshwork. Understanding the three-dimensional (3-D)
      relationships of the channels within this tissue may give insight into its normal
      function and possible changes present in the eye disease glaucoma. The purpose of
      our study was to compare laser scanning confocal microscopy with standard 1
      micron Araldite-embedded histologic sections for 3-D analysis of the trabecular
      meshwork. In addition, the study was done to determine whether computerized 3-D
      reconstruction could isolate the fluid spaces of the trabecular meshwork and
      determine the size of interconnections between the fluid spaces. Confocal
      microscopy appears comparable to 1 micron Araldite-embedded tissue sections and
      has the advantage of inherent registration of the serial tissue sections. Three
      dimensional reconstruction allowed the isolation of the fluid spaces within the
      trabecular meshwork and revealed the presence of numerous interconnections
      between larger fluid spaces. The distribution of these interconnections was
      randomly arranged, with no predilection for specific regions within the
      trabecular meshwork. This distribution of constrictions and "expansion chambers"
      may provide a clue to the mechanism by which subtle histologic changes are
      associated with increased ocular pressure in glaucoma.

PMID- 9195748
TI  - Analysis of sections of implanted macroporous calcium phosphate bone substitutes
      by proton-induced X-emission method and energy-dispersive spectrometry.
AB  - The osseointegration of porous calcium phosphate ceramics once implanted evolves
      in several stages. The mechanism of integration of such material usually is
      evaluated by histologic analysis. The trace elements present in bone can be
      detected in the ceramic and help to provide a semiquantitative evaluation of
      osseointegration. Two different methods of microanalysis, energy-dispersive
      spectrometry (EDS) and proton induced x-emission (PIXE) were used in this study
      to determine the appearance of trace elements (Zn, Sr, and Fe) present in bone at
      the implantation site containing the ceramic. Porous HA-ceramic cylinders were
      implanted in the cortical bone of sheep femurs for periods ranging from 2 to 36
      weeks. Thick sections of the implant-containing bone were made at the end of the
      implantation period. A scanning line with proton or electron impacts 0.5 mm apart
      was plotted from the edges of the cortical bone across the implanted ceramic and
      the resulting x-ray spectra were determined. Following EDS analysis, the sections
      were surface-stained, observed under a light microscope, and the pore volume
      occupied by bone tissue was measured. The spectra obtained by PIXE method showed
      two regions for each element characterising either the bone tissue or the
      ceramic. Zinc and strontium present in the bone tissue, but absent from the
      ceramic, appeared 8 and 12 weeks after implantation, respectively. The
      concentration of iron present in the implant decreased with time. EDS showed no
      significant level of either element in the bone or the ceramic. Histologic
      observation revealed that immature bone invaded the pores of the outer layer of
      the ceramic as early as 2 weeks after implantation. The ceramics were totally
      osseointegrated 20 weeks after implantation, although ceramic degradation
      continued for longer. In this experiment, the PIXE method was apparently
      sufficiently sensitive for monitoring the amount of trace element appearing in
      bone-implanted material.

PMID- 9195750
TI  - Biological cryo atomic force microscopy: a brief review.
AB  - Despite many successes, atomic force microscopy (AFM) of biological specimens at
      room temperature is still severely limited by at least two factors: the softness
      and the thermal motion of flexible multi-domain/subunit molecules. Both problems
      can be overcome by imaging biological structures at cryogenic temperatures. Even
      though the instrumentation is considerably more complex and earlier attempts were
      largely unsuccessful, cryo-AFM has recently been demonstrated on a number of
      biological specimens, using an AFM operated in liquid nitrogen vapor under
      ambient pressure. In this brief review, both the method of instrumentation and
      the latest biological applications are discussed. Not only has the cryo-AFM
      attained high resolution on those specimens that could not be well imaged at room
      temperature, but it has also produced potentially important information on
      several specimens. These results firmly establish the cryo-AFM as a useful and
      versatile structural probe in biology with its own unique capabilities.

PMID- 9195751
TI  - A constant compliance force modulation technique for scanning force microscopy
      (SFM) imaging of polymer surface elasticity.
AB  - A new method of force modulation scanning force microscopy (SFM) imaging based on
      a constant compliance feedback loop is presented. The feedback adjusts the
      loading force applied by the SFM tip to the surface in order to maintain a
      constant compliance beneath the tip. The new method, constant compliance force
      modulation (CCFM), has the advantage of being able to quantify the loading force
      exerted by the tip onto the sample surface and thus to estimate the elastic
      modulus of the material probed by the SFM tip. Once the elastic modulus of one
      region is known, the elastic moduli of other surface regions can be estimated
      from the spatial map of loading forces using the Hertz model of deformation.
      Force vs. displacement measurements made on one surface locality could also be
      used to estimate the local modulus. Several model surfaces, including a rubber
      toughened epoxy polymer blend which showed clearly resolved compliant rubber
      phases within the harder epoxy matrix, were analyzed with the CCFM technique to
      illustrate the method's application.

PMID- 9195752
TI  - Kinetic model for batch cellulase production by Trichoderma reesei RUT c30.
AB  - A kinetic model for batch cellulase enzyme production by T. reesei from cellulose
      substrate is constructed from literature concepts and laboratory data. The key
      concepts included were four: (i) existence of primary and secondary mycelia; (ii)
      cellulase production by secondary mycelia only; (iii) the adsorption of cellulase
      (catalyst) on the particulate cellulose (substrate), and (iv) the decline of
      cellulose reactivity with extent of conversion. The laboratory batch data were
      biomass (particulate), substrate (particulate cellulose), and product (cellulase
      enzyme and reducing sugar) concentration vs. time. The kinetic parameters were
      evaluated simultaneously through a nonlinear fitting routine, and the resultant
      model is shown to fit the data well. The model's success validates the presumed
      need to include all four concepts in reactor analysis for cellulase production.

PMID- 9195755
TI  - Purification and characterization of lipase from Aeromonas sobria LP004.
AB  - Lipase from Aeromonas sobria LP004, isolated from raw milk, was purified and
      characterized. The lipase was purified 10.29 fold to a homogeneous state by
      ultrafiltration and column chromatography on phenyl sepharose. The molecular
      weight of the lipase determined by SDS-PAGE was 97 kDa. Purified A. sobria LP004
      lipase exhibited the maximum activity at pH 6.0 and 45 degrees C and was stable
      under alkaline conditions (pH 6.5-10.0) and at temperatures lower than 40 degrees
      C. This lipase could be classified as a 1,3-position specific enzyme and its
      catalytic activity was calcium dependent. PMSF, a serine enzyme inhibitor and 2
      mercaptoethanol, a reducing agent, did not affect the enzyme activity.

PMID- 9195754
TI  - Mutant human protein disulfide isomerase assists protein folding in a chaperone
      like fashion.
AB  - Human protein disulfide isomerase with an extra 10 amino acid residues of
      AEITRIDPAM at the N-terminal was expressed in E. coli as a soluble protein
      comprising 20% of total cell proteins, and was purified to near homogeneity
      through one step of DEAE-Sephacel chromatography. The mutant enzyme, which had
      the same CD spectrum and comparable disulfide isomerase and thiol-protein
      oxidoreductase activities with that of the wild type human and bovine protein
      disulfide isomerases, also showed chaperone-like activity in stimulating the
      refolding of proteins containing no disulfide bond. The overall yield of the
      active product is about 20 mg 1-1 culture.

PMID- 9195756
TI  - Schizosaccharomyces pombe fragile mutants as a host for heterologous protein
      production.
AB  - In order to gain information about the potential interest of the
      Schizosaccharomyces pombe srb 1 fragile mutants as a host for heterologous
      protein production, the extracellular secretion of homologous and heterologous
      invertases was investigated. Under catabolic derepression the fragile srb 1
      mutants released into the extracellular medium 5-6-fold more invertase than the
      parental strain. When transformed with the SUC2 gene, which codes for
      Saccharomyces cerevisiae invertase, the srb 1-3 fragile mutant, grown under
      catabolic repression, released into the medium 3-fold more invertase than the
      wild-type transformant, even though the majority of the enzyme remained
      associated with the cell wall. Electrophoretic analysis revealed the presence in
      the fragile strains of some invertase forms with molecular weights smaller than
      their parallel wild-type strains, suggesting that the srb 1 mutants may
      underglycosylate not only their homologous but also the heterologous proteins.

PMID- 9195753
TI  - Isolation, cloning and characterisation of the abiI gene from Lactococcus lactis
      subsp. lactis M138 encoding abortive phage infection.
AB  - Plasmid pND852 (56 kb) encodes nisin resistance and was isolated from Lactococcus
      lactis ssp lactis (L. lactis) M138 by conjugation to L. lactis LM0230. It
      conferred strong resistance to the isometric-headed phage phi 712 and partial
      resistance to the prolate-headed phage phi c2. A 2.6 kb HpaII fragment encoding
      phage resistance was cloned into the streptococcal/Bacillus hybrid vector pGB301
      to generate pND817. The mechanism of phage resistance encoded by pND817 involved
      abortive infection and this was illustrated by a reduction in burst size from 166
      to 6 at 30 degrees C and from 160 to 90 at 37 degrees C. Partial resistance was
      therefore retained at 37 degrees C. DNA sequencing revealed that the abortive
      infection was encoded by a single open reading frame (ORF), designated abiI,
      encoding a 332 amino acid protein. Neither abiI nor the predicted product showed
      significant homology to any existing sequence in the GenBank database. Frame
      shift mutation at the unique EcoRI site within the ORF resulted in loss of the
      Abi+ phenotype, confirming that the ORF is responsible for the encoded phage
      resistance.

PMID- 9195757
TI  - Human endothelial cell lines established by mutated forms of the simian virus 40
      large T oncogene.
AB  - The large T oncoprotein of Simian Virus 40 is widely used to improve the growth
      characteristics of primary cells in culture. Beside growth stimulation and
      immortalization, expression of the large T protein in human cells frequently
      leads to a loss of differentiated characters and changes in the karyotype. We
      have constructed mutated forms of the large T protein by deletion of various
      fragments of the DNA binding domain to test, whether this region is responsible
      for undesired influences on cell differentiation. After transfection into human
      umbilical vein endothelial cells, the resulting cell lines showed no improvement
      in expression of the differentiation marker von Willebrand factor compared to
      cell lines transfected with the wild type oncogene. Changes in the karyotype were
      still observed. Our results contribute to the mapping of functional domains of
      the large T protein. The truncated large T proteins retained growth stimulating
      activity after removal of 111 and 241 amino acids of the DNA binding region.

PMID- 9195758
TI  - Improvement of expression and secretion of a fungal xylanase in the rumen
      bacterium Butyrivibrio fibrisolvens OB156 by manipulation of promoter and signal
      sequences.
AB  - Promoters and signal sequences for expression and secretion of a fungal xylanase
      encoded by a modified Neocallimastix patriciarum xynA cDNA in the rumen
      bacterium, Butyrivibrio fibrisolvens OB156, were investigated. Successful
      expression of the fungal xylanase in OB156 was obtained using the putative
      xylanase promoter from B. fibrisolvens strain 49. Replacing the putative -35
      region sequence (TTGCAC) of the xylanase promoter with the sequence TTGACA by
      mutagenesis reduced the fungal xylanase expression level 4-fold in OB156,
      indicating that this B. fibrisolvens strain did not efficiently recognise the E.
      coli consensus -35 sequence. Reduction of the spacer length between the -35 and 
      10 regions of the xylanase promoter from 18 to 17 base-pairs (bp) considerably
      increased the expression levels of the fungal enzyme in both E. coli and OB156.
      Insertion of a pUB110 mob promoter upstream of the xylanase promoter also
      significantly improved the fungal xylanase expression. Secretion of the fungal
      xylanase mediated by the alpha-amylase signal peptide from B. fibrisolvens strain
      H17c was efficient in E. coli, but very poor in OB156. An increase in the
      hydrophobicity of the signal sequence resulted in a 4-fold increase in the
      extracellular portion of the fungal xylanase in OB156, indicating marked
      improvement in xylanase secretion efficiency. The recombinant plasmids and
      xylanase expression/secretion cassettes were found to be stable in OB156 after
      prolonged cultivation (100 generations) in the absence of antibiotic selection.
      These results suggest that the rumen bacterium B. fibrisolvens can be manipulated
      to produce and secrete a eukaryotic extracellular protein with stable maintenance
      of the expression cassette in plasmid form.

PMID- 9195759
TI  - Synthesis of cell-wall glycoproteins and their characterization in oat
      coleoptiles.
AB  - D-[U-14C]Glucosamine was rapidly taken up by oat coleoptile segments and
      metabolized to radioactive UDP-N-acetylglucosamine, which acted as specific
      glycosyl donor for the synthesis of glycolipids and cytosolic, membrane-bound and
      cell-wall glycoproteins. Cell-wall glycoproteins were solubilized from the walls
      by either cell-wall-degrading enzymes or chemical extractants. The solubilized
      cell-wall glycoproteins in the presence of peptide N-glycosidase F released
      oligosaccharide chains higher than seven glycosidic residues. The combined action
      of peptide N-glycosidase F and N-acetyl-beta-D-glucosaminidase on cell-wall
      glycoproteins indicated the presence of N-acetylglucosamine residues beta-1,2
      linked to mannose. Less than 9% of the radioactive oligosaccharide chains was
      released from the solubilized cell-wall glycoproteins when treated with 0.5 M
      NaOH at 20 degrees, whereas more than 45% of the radioactivity was released in
      the presence of 1 M NaOH at 50 degrees. The high hydrolytic sensitivity of cell
      wall glycoproteins to peptide N-glycosidase F, N-acetyl-beta-D-glucosaminidase
      and NaOH at 50 degrees indicated that most N-acetylglucosamine residues were
      incorporated into N-linked cell-wall glycoproteins. Further evidence of this was
      obtained by the use of inhibitors of biosynthesis and processing of N-linked
      glycoproteins.

PMID- 9195760
TI  - Vacuolar uptake of the phytoalexin medicarpin by the glutathione conjugate pump.
AB  - We have studied the uptake of [3H]-medicarpin and its glutathione conjugate(s)
      into vacuolar membrane vesicles from etiolated hypocotyls of mung bean (Vigna
      radiata). Unconjugated medicarpin is taken up at a low rate in the presence or
      absence of MgATP. However, [3H]-medicarpin-glutathione conjugate(s), prepared by
      incubation of medicarpin with a total maize glutathione S-transferase
      preparation, is taken up more than four-fold faster than medicarpin in the
      presence of MgATP, and this uptake is MgATP-dependent. Uptake of medicarpin
      glutathione was not significantly inhibited by the ionophore gramicidin-D, but
      was strongly inhibited by vanadate and the alternative transport substrate S-(2,4
      dinitrophenyl) glutathione. Our results demonstrate, in a model system, the
      potential utilization of the high affinity, high capacity, uncoupler-insensitive
      glutathione conjugate pump for the vacuolar transport of an isoflavonoid
      phytoalexin.

PMID- 9195761
TI  - Bioactive annonaceous acetogenins from Rollinia mucosa.
AB  - Two new bioactive Annonaceous acetogenins, rollitacin (1) and rollinacin (2),
      along with one known acetogenin, javoricin, were isolated from the ethanolic
      extract of the leaves of Rollinia mucosa. Compounds 1 and 2 exhibited selective
      inhibitory effects among six human solid tumour cell lines. The structural
      elucidations of 1 and 2 were achieved by various spectroscopic analyses and
      chemical derivatizations.

PMID- 9195762
TI  - Oligosaccharide polyesters from roots of Polygala fallax.
AB  - Five new oligosaccharide polyesters, fallaxoses A-E, along with four known ones,
      reiniose D, senegose G, tenuifolioses C and P, were isolated from the roots of
      Polygala fallax. Fallaxoses A-E were elucidated as 3-O-{4-O-[beta-D
      glucopyranosyl-(1-->4)- alpha-L-rhamnopyranosyl]-feruloyl}-beta-D-fructofuranosyl
      (2-->1)-(4,6-di-O-benzoyl)-alpha-D-glucopyranoside, 3-O-{4-O-[beta-D
      glucocopyranosyl-(1-->3)-(2-O-acetyl)- alpha-L-rhamnopyranosyl]-feruloyl}-beta-D
      fructofuranosyl-(2-->1)- (4, 6-di-O-benzoyl)-alpha-D-glucopyranoside, 1-O-p
      coumaroyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)- [beta-D-glucopyranosyl-(1
      ->2)]-[6-O-acetyl-beta-D-glucopyranosyl- (1-->3)]-(4-O-p-coumaroyl)-alpha-D
      glucopyranoside, 1-O-p-coumaroyl-(3-O-benzoyl)-beta-D-fructofuranosyl-(2-->1)-
      [beta-D-glucopyranosyl-(1-->2)]-[6-O-acetyl-beta-D-glucopyranosyl-(1-->3 )]-(4-O
      feruloyl)-alpha-D-glucopyranoside, 1-O-feruloyl-(3-O-benzoyl)-beta-D
      fructofuranosyl-(2-->1)- [beta-D-glucopyranosyl-(1-->2)]-[beta-D-glucopyranosyl-
      (1-->3)-(6-O-acetyl)-beta-D-glucopyranosyl-(1-->3)]- (6-O-feruloyl)-alpha-D
      glucopyranoside, respectively, by spectroscopic and chemical means.

PMID- 9195763
TI  - Cyclic octapeptides from Stellaria dichotoma var. lanceolata.
AB  - Two new cyclic octapeptides, dichotomin H, cyclo(-Ala-Pro-Thr-Phe-Tyr-P ro-Leu
      Ile-), and dichotomin I, cyclo(-Val-Pro-Thr-Phe-Tyr-Pro-Leu-Ile-) have been
      isolated from the roots of Stellaria dichotoma L. var lanceolata Bge., and their
      structures were elucidated by extensive two-dimensional NMR methods and chemical
      degradation.

PMID- 9195764
TI  - Clinical and demographic characteristics of migraine in urban children.
AB  - OBJECTIVE: To establish the frequency, symptoms, duration, and treatment methods
      of childhood migraine in an urban area. DESIGN: Self-administered questionnaire
      survey. The questionnaire was designed according to criteria suggested by the
      International Headache Society (IHS). PARTICIPANTS: In 1994, with the help of
      school officials in 41 elementary and middle schools in the Greater Cleve-land
      Area, 18,000 questionnaires were distributed to the parents of schoolchildren who
      ranged in age from 5 to 13 years. RESULTS: Of the total 2572 respondents, 222
      children (8.6%) met the IHS criteria for migraine. Male to female ratio was 1:1.2
      (99:120), 65.8% had a positive family history of migraine, 30.6% had onset of
      migraine at 4 to 5 years of age, and 54.1% reported having an aura (71% of these
      were visual aura). The headaches were mostly pulsating, poorly localized, lasted
      about 2 to 12 hours, and were aggravated by motion, noise, and bright light. The
      associated symptoms were nausea, vomiting, photophobia, and phonophobia. During
      the attack, 43% of the migraineurs had to stay in bed, and 27% were unable to
      attend school. Only 19.8% of the migraineurs were diagnosed to have migraine by
      their physicians, and most of these had not received treatment. CONCLUSION: This
      study in an urban area indicates that childhood migraine is a common, often
      underdiagnosed disorder that causes significant suffering for children and their
      families.

PMID- 9195765
TI  - Prevalence and clinical features of chronic daily headache in a headache clinic.
AB  - Although chronic daily headache is regarded as a syndrome encountered in headache
      clinics, clinical characteristics have only rarely been studied and the condition
      has not been documented in Thailand. To investigate the prevalence as well as
      clinical features of chronic daily headache in Thai patients, 220 patients
      visiting Chulalongkorn Headache Clinic were examined. Sixty cases (27.3%) were
      diagnosed as suffering from chronic daily headache (male to female ratio, 1:5.7).
      The average age of these patients was 32.7 +/- 9.6 years. Based on the
      International Headache Society (IHS) criteria, 30% of patients with chronic daily
      headache could be diagnosed as suffering from migraine and 36.7% from chronic
      tension-type headache, whereas the remainder had combined features of both
      headache types and were not classifiable. Diffuse steady pain was the most common
      headache type reported (65%), however, associated features characteristic of
      migraine were often noted. These included photophobia (70%), phonophobia (56.7%)
      and nausea (43%). Thirty-four cases (56.7%) reported that their headache could be
      aggravated by stress. Daily use of analgesics was reported in 58.3% of cases. We
      concluded that chronic daily headache is a common problem. Although the mechanism
      has not been fully clarified, the prevalence of associated psychological factors
      and analgesic overuse imply their involvement in the pathogenesis of this
      condition. The criteria of the IHS are not entirely suitable for diagnosis and
      classification of this disorder, and modification of this classification system
      is needed.

PMID- 9195766
TI  - 'Skin roll' ('pinch and roll') test: skinfold thickness and tenderness.
AB  - Skinfold thickness and tenderness are variables that have been used in the
      diagnosis of headaches of cervical origin. In order to assess these variables in
      actual patients, the normal limits have to be properly known. Skinfold thickness
      and tenderness during the "skin roll" ("pinch and roll") test were, therefore,
      investigated simultaneously in a group of 95 healthy individuals. Three positions
      (trapezius, mandibular, and supraorbital areas) were used. The following values
      for skinfold thickness in healthy individuals during the skin roll test were
      obtained: trapezius position 5 to 26 mm (mean 11.2 mm, SD 3.9), mandibular 3 to
      12 mm (mean 6.5 mm, SD 1.8), and supraorbital 3 to 9 mm (mean 4.6 mm, SD 0.8).
      Strong positive correlation was found between subject height and skinfold
      thickness in the mandibular position. Skinfold thickness in the mandibular (P =
      0.003), as well as in the trapezius position (P = 0.023) correlated positively
      with age. In 13 individuals (13.7%), tenderness to a varying extent was found in
      the shoulders (trapezius position). No pain was recorded in the other positions.
      No correlation was found between skinfold thickness and tenderness (P = 0.66).

PMID- 9195767
TI  - Idiopathic intracranial hypertension and seventh nerve palsy.
AB  - Patients with idiopathic intracranial hypertension may occasionally present with
      coexisting lower motor neuron facial weakness. This study reviews a 6-year
      experience at Mayo Clinic. The aim of this study was to determine the possible
      association of idiopathic intracranial hypertension and facial paresis. Two cases
      were identified. Both fulfilled the modified Dandy's diagnostic criteria for
      idiopathic intracranial hypertension. Treatment consisted of steroids in one, and
      emergent optic nerve sheath fenestration in the other. The cranial nerve palsies
      resolved in both cases.

PMID- 9195768
TI  - The site of common side effects of sumatriptan.
AB  - Atypical sensations following the use of subcutaneous sumatriptan are common, but
      of uncertain origin. They are almost always benign, but can be mistaken for a
      serious adverse event by the patient. Two patients are presented with tingling or
      burning sensations limited to areas of heat exposure or sunburn. In these
      individuals, side effects are most likely generated superficially in the skin.

PMID- 9195769
TI  - Chronic intractable headache in a patient with Marfan's syndrome.
AB  - A 30-year-old woman with Marfan's syndrome had chronic intractable headaches and
      spontaneous intracranial hypotension. The pain was concentrated over the
      occipitonuchal region, had elements of both migraine and tension headache, and
      was often aggravated by postural change. Myelography showed multiple, large,
      lumbosacral arachnoid diverticula. Radioisotope cisternography revealed a
      halolike accumulation in the lumbosacral region and rapid uptake of isotope in
      the urinary bladder, indicating cerebrospinal fluid leakage. Epidural blood
      patching brought immediate relief from the positional headaches. We concluded
      that patients with Marfan's syndrome and undifferentiated chronic headaches
      should be radiologically evaluated for spinal meningeal defects.

PMID- 9195770
TI  - Antihistamine responsive cluster headache in a teenaged girl.
AB  - Episodic cluster headache is a well-recognized entity usually starting in the
      second decade of life. Uncommonly, the first typical symptoms may present in the
      first decade of life, but are rarely recognized as such during childhood. We
      report a 12-year-old girl who presented with a 1-year history of bouts of right
      sided hemicrania with ipsilateral, clearly demarcated, redness and itching of the
      skin of the face, lasting from 15 minutes to 2 hours per day. The episodes
      recurred up to several times daily for a few days and were followed by remissions
      lasting up to 2 months. Thorough investigations failed to prove any definite
      cause. Antihistamine prophylaxis, first with astemizole and then with loratadine,
      proved to be very effective. During the follow-up period of more than 3 years,
      such a prophylactic regimen provided excellent relief, with only two relapses due
      to noncompliance. We suggest that in a sequential treatment trial for cluster
      headache during childhood, antihistamines should have their place, especially in
      those cases where clinical evidence may suggest histamine involvement.

PMID- 9195771
TI  - Incomplete analgesic effect of lanreotide in acromegaly.

PMID- 9195772
TI  - Human factor-dependent leukemia cell lines.
AB  - To date several factor-dependent leukemia cell lines have been established. These
      cell lines have greatly contributed to the analyses of cytokine-mediated cellular
      signaling mechanisms involved in cell proliferation, differentiation and
      survival. In addition, they are ideal and practical models for testing the
      hypothesis regarding leukemogenesis. Taken together, factor-dependent leukemia
      cell lines are expected to be useful for studies on cell biology and development
      of new cancer therapeutics.

PMID- 9195773
TI  - Myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDS) are a group of clonal disorders, common
      especially in the elderly, characterised by cytopenias and dysfunctional blood
      cells. They are a cause of significant morbidity and premature mortality. The
      cause is not known in most cases. Predisposing factors that have been identified
      include cytotoxic chemotherapy, benzene and other environmental mutagens, and
      bone marrow transplantation. Clinically patients present with effects of
      deficiency of erythrocytes, neutrophils and/or platelets or the diagnosis may be
      made unexpectedly after routine blood testing. The bone marrow is generally
      hypercellular and often disorganized; abnormal in vitro cell growth is common.
      Non-random cytogenetic abnormalities are characteristic and helpful
      diagnostically; certain subtypes are associated with specific clinical and
      cytological features. Especially noteworthy are the 5q- and 7-syndromes. The
      outlook generally is poor. Death comes about from transformation to acute myeloid
      leukemia (AML), from the complications of cytopenias, or from intercurrent
      illness. Treatment is unsatisfactory except in young patients who can undergo
      allografting. Treatments of uncertain value include intensive or gentle
      chemotherapy. Of the cytokines erythropoietin and granulocyte-macrophage colony
      stimulating factor (GM-CSF) so far seem the most promising. However, for the
      majority management is limited to provision of appropriate supportive care.

PMID- 9195774
TI  - Clinical use of hematopoietic growth factors in patients with myelodysplastic
      syndromes.
AB  - In myelodysplastic syndromes (MDS), pancytopenia and defective function of
      neutrophils and platelets lead to a high risk of infectious and hemorrhagic
      complications. The progression to acute myeloid leukemia adds to morbidity and
      mortality. Supportive care including red blood cell and platelet transfusions are
      still the cornerstone of therapeutic management. However, the clinical use of the
      recombinant hematopoietic growth factors has enlarged the range of therapeutic
      applications in patients with MDS. It is possible to reverse neutropenia in MDS
      patients by administration of G-CSF (granulocyte colony stimulating factor) or GM
      CSF (granulocyte-monocyte colony stimulating factor). Because of the lower
      incidence of adverse events, G-CSF is preferable. However, neither G-CSF nor GM
      CSF have been shown to reduce the rate of severe infection or mortality from
      infection when given prophylactically. In the case of a severe infection,
      therapeutic administration of G-CSF together with antibiotics might be justified
      in otherwise neutropenic MDS patients. Preliminary data suggest it to be possible
      to identify MDS patients with a higher than 50% chance of reversal of anemia or
      transfusion dependency by treatment with high-dose erythropoietin (EPO). Since
      patients with only slight impairment of erythropoiesis and no transfusion
      dependency have the highest response rates but need EPO the least,
      pharmacoeconomic analyses are urgently needed. Controlled randomized trials will
      have to ascertain whether combinations of EPO with G-CSF or GM-CSF are of
      benefit. Clinical studies with thrombopoietin (megakaryocyte growth and
      differentiation factor) have to be initiated to find out whether thrombocytopenia
      in MDS can be reversed.

PMID- 9195775
TI  - Telomere crisis in leukemia.
AB  - Previous studies on telomere dynamics in leukemia are summarized. The 'telomere
      crisis model' is proposed to explain the clonal evolution mechanism of cancer
      cells from the standpoint of telomere biology. Future trends, including the
      development of potential telomerase inhibitors as a new class of anti-cancer
      agent, are discussed.

PMID- 9195776
TI  - Anemias in Thai patients with cirrhosis.
AB  - Anemia is a frequent complication in patients with cirrhosis. Only one study has
      been previously reported regarding the etiology of anemias in Thai cirrhotic
      patients. The diagnosis of iron deficiency in the study however was not based on
      standard criteria. Herein we report the frequency and hematological
      manifestations of various causes of anemias diagnosed by using gold standard
      criteria in 72 consecutive Thai cirrhotic patients. The diagnosis of cirrhosis
      was based on the characteristic clinical features and the ultrasonographic
      findings. The median age of the patients was 49 years; male:female was 1:1.3. The
      mean hemoglobin value was 8.3 g/dl and the mean MCV was 96.6 fl. Most patients
      revealed macrocytosis, normal WBC count and mild thrombocytopenia. Iron
      deficiency, defined as absent bone marrow iron stores, was the most common anemia
      found in 40% of the patients while folate deficiency, diagnosed when red cell
      folate was < 160 ng/ml packed RBC, was documented in 10% of the patients.
      Megaloblastosis, hemolysis and anemia of chronic disease was found in 4%, 28% and
      13% of the patients, respectively. Folate deficiency was significantly more
      common in the alcoholic patients (P = 0.01). Iron deficiency was thus the most
      common anemia in Thai patients with cirrhosis. The frequency of folate deficiency
      was not rare and the rate was comparable to data reported from western countries
      in spite of the Thai diet being relatively rich in folates.

PMID- 9195777
TI  - Long-term survival and differentiation of human peripheral blood CD34+ cells in
      SCID mice.
AB  - Human peripheral blood progenitor cells (PBPC) are currently used as a source of
      hematopoietic reconstitution by autologous transplantation after myeloabrative
      chemotherapy for malignancies. PBPC would also be useful for allogeneic
      transplantation since the collection of PBPC is much safer than that of bone
      marrow stem cells (BM). For allogeneic transplantation, it is imperative to
      confirm that PBPC contains self-renewable stem cells that can sustain a long
      lasting hematopoiesis. In the present study, we examined the reconstitution of
      human hematopoiesis in severe combined immunodeficiency (SCID) mice by
      transplanting peripheral blood CD34+ cells in which the neo gene was transduced
      as a marker. In 2 of 4 mice receiving PB-CD34+ cell transplantation, the neo gene
      appeared as early as 4 weeks and lasted as long as 24 weeks in all DNA
      preparations of bone marrow, peripheral blood and spleen cells from the SCID
      mice, while in 2 of 4 mice receiving BM-CD34+ cell transplantation, although the
      neo gene also lasted as late as 24 weeks, it did not appear as early as in the
      mice receiving PB-CD34+ cell transplantation. A similar observation was noted in
      clinical trials, i.e. the white blood cell and platelet recovered earlier by
      transplantation of PBPC than of BM. In mice who had the neo gene, we were also
      able to demonstrate by FACS the presence of human lineage specific antigen in the
      cells as late as 24 weeks after transplantation with PB-CD34+ cells, and the
      presence of human IgG in the sera 10 weeks after transplantation. These findings
      indicate that PB-CD34+ cells contain long-term repopulating stem cells which
      undergo differentiation in SCID mice.

PMID- 9195778
TI  - Outside-in signaling from integrin alpha IIb beta 3 into platelets in the absence
      of agonist-induced signaling.
AB  - Platelet agonists generate intracellular signals which lead to activation of the
      platelet membrane glycoprotein IIb-IIIa (integrin alpha IIb beta 3). The
      resulting occupancy of alpha IIb beta 3 by ligands also generates signals into
      the cell (outside-in signaling). We reported previously that unlike platelet
      agonists, the F(ab')2 fragments of an anti-alpha IIb beta 3 monoclonal antibody,
      PMA4, induced fibrinogen binding to alpha IIb beta 3 without causing
      intracellular activation. In this study, in order to determine whether outside-in
      signaling occurs in the absence of agonist-induced intracellular signals, we used
      PMA4 F(ab')2 as an inducer of fibrinogen binding to alpha IIb beta 3. PMA4
      F(ab')2-induced fibrinogen binding and subsequent platelet aggregation triggered
      tyrosine phosphorylation of several proteins including pp72syk but not pp125FAK.
      No Ca2+ influx or mobilization, thromboxane B2 synthesis, phosphorylation of
      pleckstrin or the myosin light chain, cytoplasmic alkalinization, or platelet
      shape changes, were detected. These findings suggest that, in the absence of
      agonist-induced signaling, alpha IIb beta 3 occupied by soluble fibrinogen
      generates only a limited outside-in signal.

PMID- 9195780
TI  - B-cell lymphoma accompanying monoclonal macroglobulinemia with features
      suggesting marginal zone B-cell lymphoma.
AB  - Waldenstroem's macroglobulinemia is usually closely related to a histopathologic
      subtype called lymphoplasmacytoid lymphoma in the Revised European-American
      Lymphoma (REAL) classification. Here, we report a case of B-cell lymphoma
      accompanied by monoclonal macroglobulinemia and pathologically compatible with
      marginal zone B-cell lymphoma (MZBCL) rather than lymphoplasmacytoid lymphoma.
      The patient was a 74-year-old man with lymphomatous lesions that were recognized
      as submandibular lymphadenopathy, subcutaneous tumor and bilateral orbital
      masses, but with no bone marrow involvement. The atypical lymphoid cells that
      occupied the lymph node were varied such as small cells harboring irregular
      nuclei, monocytoid B-cells, large cells with vesicular nuclei, and plasma cells.
      The tumor cells expressed CD19, CD20, IgM and kappa on their cell surfaces and
      cytoplasmic IgM, but not CD5 or CD10. These findings suggest that the clinical
      and histopathologic findings of this case are compatible with those of MZBCL
      rather than lymphoplasmacytoid lymphoma. Serum IgM was elevated up to 4080 mg/dl
      and M-proteinemia of IgM-kappa type was confirmed by immunoelectrophoresis.
      Hyperviscosity syndrome caused by monoclonal IgM was not apparent.
      Immunohistochemical study confirmed that monoclonal IgM-kappa was produced and
      secreted from the tumor cells of MZBCL. This case suggests a close relationship
      between MZBCL and lymphoplasmacytoid lymphoma, from the perspective of the
      cellular origin during B-cell differentiation.

PMID- 9195779
TI  - Effects of interleukin-11 on carboplatin-induced thrombocytopenia in rats and in
      combination with stem cell factor.
AB  - The effects of interleukin-11 (IL-11) which stimulates megakaryopoiesis and
      thrombopoiesis and/or stem cell factor (SCF) which stimulates multiple lineage
      cells in the peripheral blood by an increase in marrow cellularity on
      hematopoietic suppression in carboplatin (CBDCA)-treated rats were determined.
      CBDCA was administered to rats at a dose of 35 mg/kg as a single intraperitoneal
      bolus on day 0. IL-11 (20 micrograms/day) was given subcutaneously for 10 days
      from day 5 after CBDCA treatment. IL-11 ameliorated the suppression of
      hematopoiesis in rats treated with CBDCA. Especially, the production of the
      platelets was stimulated by IL-11 more markedly than that of cells of other
      lineages. However, the combination of SCF and IL-11 intensified the CBDCA-induced
      suppression of hematopoiesis. These findings may be helpful in the design of
      future therapies to prevent or treat thrombocytopenia induced by chemotherapy.

PMID- 9195781
TI  - Increased levels of soluble Fas antigen in the plasma of the patients with
      refractory anemia.

PMID- 9195782
TI  - Successful treatment of a Jehovah's Witness with acute promyelocytic leukemia.

PMID- 9195783
TI  - Acute effect of phlebotomy on cardiac function in patients with polycythemia
      vera.

PMID- 9195784
TI  - Gastrointestinal angiodysplasia in constitutional thrombocytopathies.

PMID- 9195785
TI  - Whole-life insurance is being offered to some persons infected with HIV.

PMID- 9195786
TI  - Delavirdine approved for use in treating HIV.

PMID- 9195787
TI  - Will failure to use OMT be grounds for malpractice?

PMID- 9195788
TI  - Evaluation of a critical pathway for stroke.
AB  - The diagnosis of stroke, which is diagnosis-related group (DRG) 014, is the
      fourth most frequent discharge DRG at Macomb Hospital Center, Warren, Michigan.
      The length of stay for stroke was 7.52 days before intervention. Quality
      improvement techniques identified areas of delay that presented opportunities for
      improvement. After the initiation of a critical pathway that begins its
      interventions in the Emergency Department, the length of stay decreased to 6.33
      days. Quality of care was also improved in delivery time of carotid artery
      ultrasound examinations, as well as in timeliness of obtaining head computed
      tomography scans and reports. This article describes the development,
      implementation, and results of a stroke critical pathway that was implemented to
      address excessive length of stay.

PMID- 9195789
TI  - Repositioning maneuver for benign paroxysmal positional vertigo (BPPV).
AB  - With vertigo, the symptom of unsteadiness is a common presenting complaint and
      the etiology protean. However, the specific subset of this patient population
      with benign paroxysmal positional vertigo (BPPV) is more defined. Cupololithiasis
      and canalithiasis are perhaps the best known and best described pathologic
      conditions resulting in vertigo. This condition occurs when otoconia from the
      utricle are displaced into the Posterior semicircular canal-cupula. The abnormal
      position of the otoconia often results in a pathological condition. The location
      of displacement is most often in the posterior semicircular canal. A better
      understanding of the etiology of BPPV has led to a simple and effective particle
      repositioning maneuver that allows the practitioner to alleviate vertigo symptoms
      for most patients using a simple manipulation.

PMID- 9195790
TI  - Guide to family practitioners for the diagnosis and treatment of depression in
      children and adolescents.
AB  - Childhood and adolescent depression is probably more common in the primary care
      setting than most physicians realize. Because depression can result in suicide,
      it must be differentially diagnosed from the more common complaints seen in
      pediatric and adolescent patients. The cause of depression is usually
      multifactorial and may include psychodynamic, cognitive, behavioral, life
      stress/socioenvironmental, biologic/biochemical, and genetic components.
      Depending on the patient's age, depression can present as mood disturbances, and
      eating and sleeping disturbances, as well as somatic complaints. With no
      laboratory tests currently available to diagnose depression, physicians must rely
      on the history and physical examination as the best diagnostic tool. To aid
      family practitioners, the authors present criteria for diagnosing depression from
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition along
      with treatment that includes psychotherapy and pharmacotherapy for the best
      possible outcome.

PMID- 9195791
TI  - Osteopathic medical considerations of reflex sympathetic dystrophy.
AB  - Review of current medical literature reveals little understanding of the
      physiology underlying the complex signs and symptoms that accompany reflex
      sympathetic dystrophy (RSD). The author surveyed the osteopathic medical
      literature and found a significant body of research documenting the physiology of
      somatic dysfunction. The manifestations of upper thoracic somatic dysfunction are
      strikingly similar to those of RSD and may offer insight into its heretofore
      unexplained physiology of this disorder.

PMID- 9195792
TI  - The evolving role of outcomes measurement and management in healthcare.
AB  - The focus on quality and accountability in healthcare has dramatically changed
      the manner in which clinical services are delivered. The traditional reliance on
      structural aspects of healthcare delivery has largely given way to a system that
      closely monitors processes and measures outcomes. Outcomes measurement has
      intuitive appeal because of its objectivity, global perspective on healthcare,
      and input from patients, providers, insurers, and payers in the healthcare
      delivery chain. Nevertheless, outcomes measures are destined to be closely linked
      to healthcare processes. Data from clinical investigations, interpreted using
      rigorously developed, evidence-based methodologies, must be used to provide
      feedback to those designing clinical processes and to continuously improve the
      quality of healthcare. As outcomes data will be crucial in evaluating the quality
      of services provided by managed care organizations in relation to their costs, it
      is imperative that osteopathic physicians become conversant with the history and
      evolution of outcomes measurement and management.

PMID- 9195793
TI  - Central nervous system ischemia after varicella infection and desmopressin
      therapy for enuresis.
AB  - A 7-year-old boy had a left-sided cerebrovascular accident 48 hours after
      beginning intranasal desmopressin acetate (DDAVP) therapy for persistent
      secondary nocturnal enuresis and approximately 2 weeks after varicella infection.
      A possible connection between desmopressin therapy or varicella infection (or
      both) and the patients neurologic symptoms is discussed, as is the relationship
      of desmopressin with hypercoagulability, Suggestions for patient/parent
      education, medical history taking, and patient surveillance are offered to
      prescribing physicians.

PMID- 9195794
TI  - Hydatidiform mole.
AB  - Hydatidiform mole is a gestational trophoblastic disease that arises from fetal
      rather than maternal tissue and can become metastatic. Most signs and symptoms
      occur late in the first trimester and are often confused with symptoms of a
      normal pregnancy and, thus, are often disregarded. The two most important
      diagnostic tools to detect this disease are the ultrasound and the quantitative
      beta-human chorionic gonadotropin assay. Treatment includes dilation and
      evacuation of the uterus and strict follow-up of quantitative beta-human
      chorionic gonadotropin levels. It is also important that the patient be placed on
      a reliable form of birth control during her follow-up period.

PMID- 9195795
TI  - Tickborne disease update.

PMID- 9195796
TI  - Air quality and public health.

PMID- 9195797
TI  - Autologous blood collection in anemic patients using low-dose erythropoietin
      therapy.
AB  - Autologous donation of blood for use during elective surgery is being recommended
      and used more frequently. Autologous donation and transfusion represent the
      safest way to handle elective surgical blood requirements because they eliminate
      the risk of transfusion-transmitted disease and alloimmunization, and
      significantly reduce the other risks associated with homologous transfusion. Many
      individuals, particularly women and the elderly, do not have sufficient initial
      hemoglobin concentration or hemopoietic reserve to effectively use autologous
      donation. Use of standard-dose recombinant human erythropoietin (rHuEPO) (600
      units/kg) to mitigate these limitations is costly. The optimal dose, interval,
      and route of administration for rHuEPO therapy has yet to be perfected. This
      article describes a program using low-dose (< 100 units/kg) rHuEPO and also
      discusses the effectiveness, cost savings, and clinical indications for the use
      of low-dose rHuEPO.

PMID- 9195798
TI  - African-American males and prostate cancer: assessing knowledge levels in the
      community.
AB  - Although the available evidence indicates that African-American males are at risk
      for developing prostate cancer, little is known about the level of awareness
      among African Americans about prostate cancer or how receptive they are to
      screening. This study examined the level of knowledge African-American males have
      about prostate cancer and the factors affecting knowledge levels. Face-to-face
      interviews were conducted among a sample of African-American males older than 25
      years. All respondents were asked if they knew what prostate cancer was (N =
      897), and those older than age 40 (N = 556) answered a series of seven questions
      related to prostate cancer. An index was created that reflected respondents level
      of knowledge about prostate cancer. Slightly more than 19% of the sample scored
      relatively high on the index related to prostate cancer knowledge, but 30%
      answered three or fewer questions correctly. Income, marital status, education,
      and type of insurance were significantly related to a respondent's level of
      knowledge. Having a regular physician and discussing prostate screening with a
      physician were both positively related to a respondent's level of understanding.
      This study indicates that African-American men do not have adequate knowledge
      about prostate cancer. Although many African Americans may be getting the
      prostate cancer message, educational efforts need to be strengthened to reach the
      less affluent and the less educated. These findings also raise questions about
      why more African-American men are not being screened and why more primary care
      physicians are not discussing prostate cancer with their African-American
      patients.

PMID- 9195799
TI  - Profile of dementia in a Nigerian community--types, pattern of impairment, and
      severity rating.
AB  - Out of 2494 subjects screened in a Nigerian community, 28 patients with dementia
      were identified. Alzheimer's disease was diagnosed in 18 patients (64.3%), 16 of
      whom had probable Alzheimer's disease. Eight patients (28.6%) had vascular
      dementia while one patient each had parkinsonism with dementia and depression
      with dementia. Patients with Alzheimer's disease were significantly older,
      predominantly females and illiterates. Cognitive deficit commonly took the form
      of memory and judgment impairment while financial mismanagement was the most
      frequent impaired activity of daily living. More than half of the cases had mild
      disease on severity rating and were comprised mainly of Alzheimer's disease
      subjects. These results confirm the higher frequency of Alzheimer's disease over
      the other types as reported in other communities.

PMID- 9195800
TI  - A comparison of AIDS-related sexual risk behaviors among African-American college
      students.
AB  - This article compares the sexual practices and risk-taking behaviors of African
      American male and female college students (n = 649) attending 4-year institutions
      in a major southeastern metropolitan area. It is a descriptive study of the kinds
      of practices that put African-American college students at a high risk of
      contracting the human immunodeficiency virus (HIV). Overall, the reported
      practices indicate that the college students studied are exposed to risk by
      certain sexual behaviors, with males reporting significantly higher frequency of
      risk behaviors than females. The percentages of male students reporting they
      engage in an array of risky sexual practices (including sex without condoms and
      anal intercourse) suggest the invulnerability to HIV apparently perceived by this
      group. Although the students overall adhere to some HIV-preventive behaviors,
      they also violate important HIV prevention practices. The findings illuminate the
      need for designing and conveying messages for African-American college students,
      and particularly for males, that impress the realities of acquired
      immunodeficiency syndrome (AIDS) as an indiscriminant disease on this group.

PMID- 9195801
TI  - Knowledge, beliefs, attitudes, and cancer screening among inner-city African
      American women.
AB  - Three hundred twenty-one inner-city African-American women were interviewed to
      determine their knowledge, attitudes, and beliefs regarding cancer and cancer
      screening, and their cancer screening histories. The women were recruited from a
      variety of sources in Atlanta and were interviewed in their homes by trained lay
      health workers. Half of the subjects had an annual household income of < $15,000.
      About half had received a Pap smear and clinical breast examination within the
      year preceding the interviews. For women > 35 years old, 35% had received a
      mammogram within the recommended interval. Younger women and women with higher
      incomes were more likely than older women and those with lower incomes to have
      received a Pap test and clinical breast examination within the preceding year,
      but income was not significantly associated with mammography histories. In
      general, women who were more knowledgeable about cancer and its prevention were
      more likely to have been appropriately screened. However, various attitudes and
      beliefs regarding cancer generally were not associated with screening histories.
      We conclude that cancer screening programs for inner-city minority women should
      focus on improving knowledge levels among older women rather than attempting to
      alter attitudes and beliefs.

PMID- 9195802
TI  - Recurrent myocardial infarction with patent coronary arteries.
AB  - Two separate episodes of severe chest pain occurred several years apart in a 25
      year-old male patient with typical clinical findings of acute myocardial
      infarction with each episode. Cardiac catheterization following the second
      infarction confirmed the presence of myocardial dysfunction with apical akinesis
      and dyskinesis. Both coronary arteries were radiologically patent; however, there
      was evidence of probable recanalization of the right coronary artery. Several
      months later, the patient developed flank pain, hematuria, progressive renal
      failure, and cardiac decompensation, and died with intractable arrhythmias. At
      autopsy, a large apical mitral thrombosis was found and was the presumptive
      source of multiple systemic emboli.

PMID- 9195803
TI  - The Howard University Cancer Center: a quarter century of excellence in cancer
      care and research (1972 to 1997).

PMID- 9195804
TI  - Non-cytotoxic control of colorectal cancer.

PMID- 9195805
TI  - The functional balance of metalloproteinases and inhibitors in tissue
      degradation: relevance to oral pathologies.
AB  - Members of the family of matrix metalloproteinases (MMPs) are key enzymes in
      normal and pathological tissue remodelling. They function at neutral pH and can
      digest synergistically all the macromolecules of the extracellular matrix.
      Biochemical and cloning studies indicate that there are three major groups: the
      specific collagenases cleave interstitial collagens; the gelatinases degrade
      other types of collagen and act synergistically with collagenases by degrading
      denatured collagens (gelatins); and the stromelysins which have broader
      specificity and can degrade basement membrane collagens as well as proteoglycans
      and matrix glycoproteins. Others in the family, but not in the major groups, are
      matrilysin, metallo-elastase, and several recently cloned membrane-bound
      metalloproteinases. Naturally occurring inhibitors, TIMPs (tissue inhibitors of
      metalloproteinases), are important controlling factors in the actions of MMPs,
      and tissue destruction in disease processes often correlates with an imbalance of
      MMPs over TIMPs. The relevance of recent molecular research to periodontal
      diseases is discussed.

PMID- 9195806
TI  - Informed consent from whom?
AB  - To obtain legally safe informed consent requires that the patient has a
      'substantial understanding' of the proposed procedure and that the doctor
      obtaining the informed consent has sufficient knowledge to explain the nature of
      the procedure to the patient. In this paper we have shown that significant
      misunderstanding exists among non-specialist junior doctors of certain common
      orthopaedic procedures and conditions. Junior doctors often lack sufficient
      technical training to fully inform their patients and thus meet legal
      requirements. The implications of this are that the onus falls even more on
      specialists to ensure that their patients receive a more detailed explanation of
      the proposed intervention.

PMID- 9195807
TI  - Performance indicators in surgery.
AB  - Performance indicators are of vital importance to surgeons today. Many different
      examples from industry are being utilized by present management in the NHS, but
      surgeons and most medical professionals remain sceptical. This article introduces
      some of the performance indicators in use and examines concepts in the context of
      surgical practice.

PMID- 9195808
TI  - Recurrent laryngeal nerve dysfunction following carotid endarterectomy.
AB  - Recurrent laryngeal nerve dysfunction is a significant complication of carotid
      endarterectomy and vocal cord paralysis is a major source of morbidity. This
      study prospectively assessed patients undergoing carotid endarterectomy to
      determine the nature and frequency of vocal cord damage and attempt to identify
      avoidable factors. Fifty consecutive patients undergoing carotid endarterectomy
      for symptomatic disease were studied. A standardized surgical technique was used
      emphasizing identification of the vagus nerve and minimal disturbance of the
      surrounding tissues. All patients underwent pre-operative and post-operative (day
      2) indirect laryngoscopy and videostroboscopy. Pre-operative assessment found
      asymptomatic compensated vocal cord paralysis in one patient who had previously
      had a stroke. Post-operative laryngoscopy revealed asymptomatic impaired vocal
      cord mobility in three patients (6%) all of whom recovered completely. In
      addition six patients (12%) developed post-operative hoarseness of whom five have
      fully recovered. The remaining patient (2%) developed vocal cord paralysis which
      is permanent to date. This prospective study demonstrates that recurrent
      laryngeal nerve dysfunction is a common but often transient complication of
      carotid endarterectomy. The incidence of vocal cord paralysis in this group was
      less than many of the reported series. This could be due to the technique of
      minimal dissection which may prevent disturbance of the vagal segmental blood
      supply. Pre-operative vocal cord assessment is essential in all patients
      undergoing carotid endarterectomy.

PMID- 9195809
TI  - Distal anastomotic vein cuff and the use of an internal vessel occluder.
AB  - In the absence of adequate autogenous vein for tibial artery bypass in limb
      salvage surgery, the use of prosthetic grafts with a distal anastomotic vein cuff
      or patch has shown promising results. Here, we describe how the Florester
      Internal Vessel Occluder (Meadox UK, Bedfordshire, UK) can facilitate the
      construction of a distal anastomotic vein cuff.

PMID- 9195810
TI  - Emergency abdominal surgery in the elderly.
AB  - A retrospective survey of 152 patients undergoing emergency abdominal surgery was
      carried out to examine factors which may have affected the outcome of surgery.
      The operative diagnosis and procedure carried out, pre-operative health of the
      patient, duration of surgery and grade of surgeon were studied to assess whether
      these factors had any bearing on the eventual outcome. A large variety of
      surgical emergencies were treated but none of the factors under study were
      related to the eventual morbidity or mortality recorded. The overall mortality
      among these patients was 25% which concurs with other studies. The presence of an
      obstructing cancer of the left colon or upper gastro-intestinal haemorrhage had a
      particularly poor outcome. Most patients were discharged to their own homes
      within 3 weeks of admission and they did not comprise an undue burden on the
      surgical service.

PMID- 9195811
TI  - A review of nipple discharge in Chinese women.
AB  - Nipple discharge was the presenting complaint in 104 patients (1.5%) from a
      series of 7000 women who were seen in a breast clinic over a 13-year period.
      Complete follow-up information was available in 66 Chinese patients. The mean age
      at presentation was 47 years. Twenty-six patients (39%) were postmenopausal.
      Unilateral discharge (92%) from a single duct (77%) was the main finding. There
      were five patients (8%) with proven breast cancer; benign duct papilloma was
      found in 17 patients. Multivariate analysis showed that cancer was most likely in
      women over the age of 55 (P < 0.05) and when the discharge was bloody (P < 0.05).
      Ductography was also found to be useful in the diagnosis of duct papilloma (P <
      0.02).

PMID- 9195813
TI  - Management of post-operative recurrent diverticulitis: a review of the
      literature.
AB  - Recurrent abdominal symptoms following resection for diverticular disease occur
      in 1-10% of patients. Not all of these patients have recurrent diverticulitis.
      Other conditions such as carcinoma, irritable bowel syndrome, inflammatory bowel
      disease and ischaemic colitis should be considered in the differential diagnosis.
      A thorough investigation including computerized tomography (CT) scanning,
      contrast studies and colonoscopy must be undertaken. The cause of recurrent
      diverticulitis may be the result of inadequate previous resection or progression
      of disease. Re-resection has been required in 0-3.1% of patients in a collected
      series. Re-resection may be technically demanding although permanent colostomy is
      usually not necessary. The best method of prevention is adequate initial
      resection.

PMID- 9195812
TI  - Vesico-colic fistulae in the Grampian region: presentation, assessment,
      management and outcome.
AB  - Over a 12-year period, 67 patients presented with a vesico-colic fistula. The
      mean age was 69 years (range 19-96 years), with symptoms predominantly referred
      to the urinary tract. Cystoscopy and barium enema confirmed the presence of a
      fistula in 60 and 44% of patients respectively. A computerized tomography (CT)
      scan, used in only seven patients, revealed the fistula in each case. The
      underlying pathology included diverticular disease (62%), carcinoma (27%) and
      inflammatory bowel disease (6%). Fifty-one patients proceeded to surgery, of whom
      32 (63%) had a sigmoid/recto sigmoid resection with primary anastomosis, and 13
      (25%) a Hartmann's procedure. A diverting colostomy alone was employed to
      palliate cases of widespread carcinoma. No patient subsequently had the
      Hartmann's reversed. In addition to colonic resection, 48 (92%) patients had a
      simultaneous bladder procedure, varying from simple oversew in 32 (70%) patients
      to cystectomy and ileal conduit in three (6%). Wedge excision with primary
      bladder closure was practised in 12 (24%). Fistula recurrence occurred in seven
      (14%) patients, and the 30-day mortality was 10%. Surgery for vesico-colic
      fistula has an appreciable morbidity and mortality, yet if offers the only hope
      of achieving permanent symptomatic control.

PMID- 9195814
TI  - Anal and perianal tuberculosis: a report of three cases in 10 years.
AB  - From the computerized pathology record, three cases of anal and perianal
      tuberculosis were encountered in the Prince of Wales Hospital, Hong Kong during
      the last 10 years. The clinical history, examination findings and relevant
      investigations were reviewed retrospectively. Comparison was made with previous
      literature. Emphasis was put on the diversity of clinical presentations including
      acute perianal abscess, chronic anal ulcer and fistula in ano. It is concluded
      that a high index of suspicion is important to ensure an early diagnosis.

PMID- 9195815
TI  - The Rotaflex total knee replacement--a 5 year review.
AB  - We report the results of a retrospective analysis of 43 patients who received 56
      Rotaflex total knee arthroplasties, with a mean follow-up of 55.7 months. The
      British Orthopaedic Association (BOA) knee assessment protocol was used in
      evaluating the clinical results. Two patients could not receive post-operative
      scores. In the remaining 54 knees, the mean pre-operative score was 25.6,
      improving to 30.8 post-operatively. Ten knees showed a decrease in knee score,
      two were unchanged and 42 improved. The greatest improvements were in pain relief
      and maximum flexion. Wound infection and dehiscences were common, the latter
      requiring further surgery in five cases. Later, there were eight fractures
      involving the prosthesis, seven dislocated or subluxed patellae, two deep
      infections and three cases of severe aseptic loosening. A common feature was
      severe patellar wear, due to the design fault of an absent femoral groove. The
      high rate of complications and poor functional result of the Rotaflex knee
      preclude its use in current practice.

PMID- 9195816
TI  - Osteomyelitis occurring in the zygomatic bone.
AB  - Osteomyelitis of bones in the middle third of the face is rare, especially in
      westernized populations. The actiology is usually due to odontogenic sources or
      infected fracture sites. An unusual case of osteomyelitis of the zygomatic bone
      resulting from the use of radiotherapy in the management of recurrent basal cell
      carcinoma is presented. This illustrates a late complication of therapy for a
      cancer which commonly occurs in the head and neck region and is rapidly
      increasing in incidence in the UK.

PMID- 9195817
TI  - Pulse oximetry as a guide to early division of pedicled flaps.
AB  - The use of pulse oximetry in monitoring time for early division of pedicled flaps
      is discussed. Two cases of groin flaps are presented in which pedicle division
      was performed on days 10 and 15 respectively, without skin loss.

PMID- 9195818
TI  - Sporadic medullary thyroid carcinoma associated with toxic multinodular goitre.
AB  - First described in 1959, medullary thyroid carcinoma (MTC) arises from
      parafollicular C cells distributed throughout the thyroid, and may occur in one
      of two clinical forms, sporadic (80%) or familial. Familial MTC may present as a
      palpable thyroid nodule, but may also be diagnosed by screening relatives of an
      index case for a raised basal serum calcitonin or a rise in calcitonin following
      a stimulated pentagastric test. Both tests are highly sensitive for C-cell
      hyperplasia and MTC. Sporadic cases of MTC most commonly present as asymptomatic
      thyroid nodules with normal thyroid function tests. In this note, the history of
      a patient is presented in which a sporadic MTC was associated with goitre and
      both symptoms and biochemical evidence of thyrotoxicosis.

PMID- 9195819
TI  - Ileal amoebiasis.
AB  - Whilst colonic amoebiasis and its complications are well-documented, ileal
      amoebiasis has not been described in the literature. We report the cases of two
      patients with ileal amoebiasis and outline their management and outcome. It is
      important that surgeons working in areas endemic for amoebiasis be mindful of
      this entity.

PMID- 9195820
TI  - Colonic Strongyloides stercoralis infection masquerading as ulcerative colitis.
AB  - Strongyloides stercoralis is a nematode infection which predominantly involves
      the small bowel. Spillover infection to the colon does occur, but is uncommon and
      is usually associated with an immunocompromised host. Accurate diagnosis is
      essential and, as this case demonstrates, a long history does not preclude an
      infective aetiology.

PMID- 9195822
TI  - A simple device for circumcision.

PMID- 9195821
TI  - Right-sided low inguinal pain in young women.

PMID- 9195823
TI  - Anastomoses involving the colon and rectum: an 8 year experience.

PMID- 9195826
TI  - Dietary advice in the management of diabetes mellitus--history and current
      practice.
AB  - Diet has been recognised for over three thousand years as being vital to the
      overall management of diabetes mellitus (DM). Today dietary advice for the person
      with diabetes continues to play just as an important role, not just as regards
      the day to day control but also in respect of the prevention of complications.
      The history of dietary advice for diabetes is examined as well as current dietary
      advice.

PMID- 9195827
TI  - Discussion of the controversies associated with prostate cancer screening.
AB  - Early detection of prostate cancer through screening seems to provide the best
      hope of control or possibly cure of the disease. Unfortunately, controversy and
      confusion surround the screening guidelines. Specifically, the controversy
      involves whether the screening of asymptomatic men, particularly those under age
      50, should be recommended. To date, there have been no randomised clinical trials
      which have demonstrated that screening for prostate cancer reduces mortality or
      increases life expectancy. The lack of evidence regarding the benefits of
      prostate screening and the risk of adverse effects make it important for
      clinicians to provide information to interested patients regarding the possible
      consequences before they take part in screening endeavours. Other health care
      professionals must be proactive in becoming informed about the entire prostate
      screening issue.

PMID- 9195828
TI  - Prostate cancer in the UK.

PMID- 9195829
TI  - A profile of 100 complicated cases of chronic suppurative otitis media.
AB  - A two year study of cases of chronic suppurative otitis media admitted in the
      Ear, Nose and Throat (ENT) Department of Sir Salimullah Medical College and
      Mitford Hospital from January 1991 to December 1992 was done. 112 patients of
      chronic suppurative otitis media (CSOM) were admitted during this two year
      period, out of which 100 patients (89.3%) presented with different types of
      complications and only 12 patients (10.7%) presented with no complications.
      Factors associated with the late presentation of the disorder, including poor
      socioeconomic conditions and lack of hospital facilities, are identified.
      Measures to prevent the rate of complications and hearing loss in children are
      suggested.

PMID- 9195830
TI  - Non-group A streptococci: are they pathogens in the throat?
AB  - A total of 3,184 paediatric patients with sporadic pharyngitis was studied at
      King Khalid University Hospital in Riyadh, Saudi Arabia. In addition, 478
      children without pharyngitis who were matched for age and sex were included as
      controls. Group A beta-haemolytic streptococci (beta HS) were detected
      significantly more often among the children with pharyngitis than among the
      controls (8.4% vs 2.3%; p < 0.0001). In contrast, total non-group A and group C
      beta HS were isolated at lower frequency from the sick than control children
      (0.9% vs 2.5% and 0.2% vs 1.2% respectively; p < 0.01) while other non-group A
      beta HS such as groups B, G and F were each isolated in similar frequency from
      both the sick and control children. We conclude that non-group A beta HS appear
      not to be as important as aetiological agents of sporadic pharyngitis in these
      children.

PMID- 9195831
TI  - The aetiology of mandibular fractures at an urban centre.
AB  - The objectives of this study were to determine the common aetiological factors
      leading to the fracture of the lower jaw (mandible) at an urban centre in
      England. A total of 96 patients presented to the Manchester Royal Infirmary with
      mandibular fractures during the calendar years 1991 and 1992. It was determined
      that the main aetiological factor leading to the disturbance of the mandibular
      contours was assault or interpersonal violence (74%) followed by falls, road
      traffic accidents and sporting injuries. The majority of the subjects were males
      and most of the patients were in the age group of 20-29 years. In most of the
      patients there was a unilateral pattern of injury and the angle was the most
      vulnerable area of the lower jaw to be traumatised.

PMID- 9195832
TI  - Home visits to elderly patients in Saudi Arabia.
AB  - The present study was conducted to examine the perception of participating
      physicians in hospital and primary health care (PHC) on the nature of illness
      that requires home visits, type and job description of health personnel that
      should make home visits and other prerequisites needed for successful home
      visits. A predesigned questionnaire consisting of demographic and professional
      characteristics of doctors was sent confidentially to randomly selected PHC and
      hospital doctors during the period January to June 1994. The respondents were
      asked to give their opinion on the categories of health problems that necessitate
      home visits, job descriptions of various professionals needed and the
      prerequisites for the successful running of home visits. Three hundred and ninety
      six PHC and 238 hospital doctors participated in the study. PHC doctors were
      younger, having more females and less qualified than hospital doctors. Both PHC
      doctors and hospital doctors gave priority to bed-ridden patients and lowest
      priority to mobile chronically ill patients. PHC doctors were more keen on home
      visits than hospital doctors. More PHC doctors than their hospital counterparts
      would like nurses and health visitors to be involved in nursing procedures
      performed at home except when it comes to notifying doctors about patients'
      problems. In case of stroke more hospital doctors would like physiotherapists to
      be involved than PHC doctors and vice versa in the case of osteoarthritis. Most
      PHC doctors preferred occupational therapists involvement in training patients
      and the modification of their environment to lead independent lives. More
      hospital doctors than their PHC counterparts preferred afternoon sessions for
      home visits. The respondents' views in the present study can be made use of in
      establishing a home visit programme to the Saudi elderly to need of such
      services. In addition, the number, qualifications and responsibilities of the
      various professionals involved in the visit should be re-evaluated after adequate
      implementation.

PMID- 9195833
TI  - New treatment for Parkinson's disease.

PMID- 9195834
TI  - Suicide and 'violent' death in a six-year cohort of male probationers compared
      with pattern of mortality in the general population: evidence of accumulative
      socio-psychiatric vulnerability.
AB  - The 'Health of the Nation' (Department of Health, 1992) suicide targets focus
      upon the mentally ill, but virtually ignore the mentally abnormal offender.
      Whilst forensic services deal with the severely disturbed, the majority of
      offenders remain in the community, despite long-standing psychosocial
      difficulties. This study explores the mortality rates of a six-year cohort of
      male probationers (1990-1995) with males in the general population. Male
      offenders (aged 17-54) had double the death rate, five times the 'external death'
      rate and nine times the suicide rate of the general population. This paper
      highlights the need to further improve the health-psychiatric-criminal justice
      collaboration.

PMID- 9195835
TI  - How can psychological theory help to promote condom use in sub-Saharan African
      developing countries?
AB  - Condom use for HIV prevention has been very inconsistent in most sub-Saharan
      African countries. Studies from around the continent report that knowledge about
      HIV transmission is variable and seems to be related to gender, socioeconomic and
      educational status. There is a large body of psychological knowledge about HIV
      prevention which has been applied to condom promotion campaigns in developed
      countries. These approaches to condom promotion, based on formal theory, have not
      been used on a wide scale in African countries and this paper explores ways in
      which psychological theory might be appropriately applied in a situation of high
      HIV prevalence.

PMID- 9195836
TI  - Health and safety (consultation with employees) regulations 1996.
AB  - The Health and Safety Commission (HSC) introduced the Health and Safety
      (Consultation with Employees) Regulations 1996 (HSCER) on 1st October, 1996. The
      HSCER 'top up' the existing Safety Representatives and Safety Committees
      Regulations 1997 (SRSCR). The HSCER require employers to consult with all
      employees, not just those covered by representatives appointed by recognised
      trade unions, on matters relating to health and safety. Employers have the choice
      of consulting whether directly with employees or via elected representatives.

PMID- 9195837
TI  - Re: Studies of risks associated with technological development in Nigeria.

PMID- 9195839
TI  - Dedication to the health of our state.

PMID- 9195838
TI  - Interview with Carl Restivo, Jr, MD. Interview by Bill Berlin.

PMID- 9195840
TI  - Population and labor force growth in New Jersey: 1994-2005.

PMID- 9195841
TI  - Radiology/pathology conference at UMDNJ.

PMID- 9195842
TI  - Emerging infectious diseases: new and resistant strains of HIV.

PMID- 9195843
TI  - Children and obesity: flunking the fat test.
AB  - Children appear to be following a disturbing trend set by adults-more children
      are overweight, yet fewer are physically active. According to a 1995 National
      Center for Health Statistics study, 4.7 million American children ages 6 to 17
      years are severely overweight. Another estimate from the New Jersey Department of
      Health and Senior Services indicates that one in four children weighs too much.

PMID- 9195844
TI  - For want of clean needles: race and the spread of AIDS.

PMID- 9195845
TI  - Voice recognition: talking to your computer.

PMID- 9195846
TI  - The PRO: essential partner in health care quality improvement.
AB  - The health care profession has undergone radical changes and shifts that no one
      associated with the medical field in New Jersey would have predicted only a
      decade ago. As cost containment, managed care, mergers, and downsizing dominate
      New Jersey's health care agenda, the concept of quality-how to define it, how to
      measure it, and how to improve it-often takes a back seat to these issues.

PMID- 9195847
TI  - SPECT versus planar 99mTc-sestamibi myocardial scintigraphy: comparison of
      accuracy and impact on patient management in chronic ischemic heart disease.
AB  - A head-to-head comparison between 99mTc-sestamibi SPECT and planar myocardial
      imaging using dipyridamole low-level exercise stress was performed for the
      assessment of coronary artery disease (CAD) and for the impact on patient
      management in 78 patients (pts) who underwent coronary arteriography. Overall
      sensitivity and specificity for detection of CAD were 82% and 82% for SPECT, and
      78% and 73% for planar imaging, respectively (both NS). Compared to planar
      imaging the sensitivity of SPECT imaging was significantly higher for detecting
      left anterior descending (p = 0.02) and left circumflex (p = 0.03) coronary
      artery disease. In predicting distally located stenoses, SPECT was significantly
      superior to planar imaging for the left circumflex artery (p = 0.025).
      Concordance analysis of perfusion status showed agreement in 308 of 390 (79%) of
      coronary flow regions both with respect to the presence or absence of perfusion
      and to the reversibility or irreversibility of defects (kappa = 0.60, SE 0.04).
      Stress-induced perfusion defects were significantly more detected by SPECT than
      by planar imaging (p < 0.001). Based on SPECT findings 31 pts were proposed for
      revascularization compared to 30 pts based on planar imaging (NS). Overall there
      was agreement in 65 (83%) pts regarding treatment strategy. We conclude that in a
      head-to-head comparison SPECT provided improved diagnostic value compared with
      planar imaging. However, with respect to patient treatment, the superiority of
      SPECT was not always translated into improved patient management.

PMID- 9195848
TI  - Role of transchelation in the uptake of 99mTc-MAb in liver and kidney.
AB  - High radioactivity in liver and kidney after administration of 99mTc-labeled
      antibodies is a major detriment to the use of radiolabeled antibodies for
      diagnosis and therapy. In the present study, the uptake mechanism of
      radioactivity by liver and kidney involving 99mTc moiety was investigated. The
      data of in vitro and in vivo thiol transchelation studies, biodistribution
      alteration of 99mTc-MAb after specific modulation of endogenous thiol containing
      compounds, and the finding of 99mTc-labeled cysteine and GSH in bile, urine and
      kidney after administration of 99mTc-MAb demonstrated that transchelation by
      thiols (cysteine and GSH) played an important role in the localization of
      radiotracer from 99mTc MAb in normal tissues such as liver and kidney.

PMID- 9195849
TI  - Doppler-broadening of positron annihilation in a biological environment.
AB  - The aim of this study was to investigate the Doppler effect of the 511 keV gamma
      peak from positron annihilation in biological matter. The broadening of the
      annihilation peak is due to positron annihilation with electrons that have high
      momentum. In aqueous solutions annihilation depends on the temperature and it is
      linked positronium formation. Measurements in vivo, on human brain, were taken
      during the diagnosis of positron emission tomography (PET) on healthy patients by
      injecting them with the beta emitter of short lifetime 18F. The Doppler
      broadening in biological tissues rich in water content decreased significantly
      compared to biological solutions and water.

PMID- 9195850
TI  - Exploration of novel strategies to enhance monoclonal antibodies targeting.
AB  - This paper highlights the major obstacles and prospects of antibody targeting for
      the radioimaging and therapy of human malignant lymphomas and more challenging
      solid tumors. To improve the therapeutic potential of monoclonal antibodies, we
      have focused our attention on the development of new and successful methods to
      augment antibody uptake in the tumor. These approaches include the use of
      radiolabeled streptavidin to target biotinylated monoclonal antibodies already
      bound to tumor, pretreatment with vasoactive immunoconjugates, and the use of
      chemically modified antibodies. Because of the promising preclinical data
      obtained with these three newer approaches, plans are underway to test them in
      the clinic. More generally, these approaches are applicable to the use of other
      monoclonal antibody/tumor systems for the diagnosis and therapy of human cancers
      and related diseases.

PMID- 9195851
TI  - Malignant paraganglioma of the prostate: case report, depiction by meta
      iodobenzylguanidine scintigraphy and review of the literature.
AB  - OBJECTIVE: To describe the 123-I-MIBG scintigraphic, CT, MRI, operative and
      pathological findings in a case of malignant prostatic paraganglioma and to
      review the literature on this very rare tumor. EXPERIMENTAL DESIGN: Clinical
      imaging and pathological correlation of data in a referred patient. SETTING:
      Regional referral center and tertiary referral academic medical center. PATIENT:
      17 year old man presenting with painless hematuria and a large prostatic mass.
      Interventions and measures. Renal ultrasound, transrectal ultrasound, ultrasound
      guided prostatic biopsy, pelvic CT and MRI, planar and SPECT 123-I-MIBG
      scintigraphy, and surgical exploration. RESULTS: The patient had a significant
      hydronephrosis of the left kidney and marked enlargement (120 ml) of the prostate
      gland by ultrasound. Ultrasound guided biopsies of the prostate and a left pelvic
      lymph node revealed a neuroendocrine tumor staining positive for chromogranin. CT
      and MRI revealed a large tumor of the prostate invading the seminal vesicles,
      bladder and rectum with extensive pelvic lymph node spread. The primary tumor and
      one of the nodes were shown to be 123-I-MIBG avid confirming the neuroendocrine
      nature of the tumor. The lesion was unresponsive to chemotherapy and unresectable
      at surgical exploration. CONCLUSIONS: To date there have only been 5 reports of
      prostatic paragangliomas. To our knowledge this is the first to have been studied
      by MIBG scintigraphy and like most paragangliomas it was MIBG-avid.

PMID- 9195852
TI  - Evaluation of renographic and metabolic parameters in human kidney
      transplantation.
AB  - BACKGROUND: The aim of this work is to demonstrate that the value of the mean
      transit time (MTT) obtained from the 99mTc-MAG3 renogram deconvolution is related
      to the levels of adenine nucleotides determined in cortical biopsies from
      transplanted kidneys. METHODS: The functional state was estimated by means of the
      MTT and the initial height (H0) of the renal retention function obtained from the
      99mTc-MAG3 renogram deconvolution and by the measure of adenine nucleotides
      obtained from biopsies. We studied 30 kidney graft recipients, 25 normal
      functioning grafts (NFG) and 5 with acute tubular necrosis (ATN). RESULTS: The
      MTT is significantly longer for ATN (p < 0.001). The initial uptake values (H0)
      are significantly lower for ATN (p < 0.001). The sum of adenine nucleotides (SAN)
      is significantly greater for NFG than for ATN (p < 0.001). The values of the MTT
      seem to reflect the energy state of the cells in transplanted kidney. CONCLUSION:
      The analysis of MTT may be indicative of the functional metabolic recovery and
      thus it may be predictive of the renal graft function at least in the same extent
      than the biochemical analysis of a cortical renal biopsy immediately after blood
      reperfusion of the tissue.

PMID- 9195853
TI  - Detection of hibernated myocardium using intracoronary technetium-99m-sestamibi.
AB  - A possible limitation of intravenously administered perfusion tracers in
      detecting hibernating myocardium is their poor availability in low-flow areas. We
      have hypothesized that intracoronary administration might overcome such a
      limitation. In two patients with a previous anterior myocardial infarction and a
      severe residual stenosis of the left anterior descending coronary artery,
      technetium-99m-sestamibi (74 MBq) was selectively injected into the infarct
      related coronary artery before successful PTCA. SPECT imaging was carried out 1
      hour after the PTCA. In patient 1, evident tracer uptake was detected in the
      majority of the antero-apical dys-synergic area, previously characterized by a
      severe irreversible defect (less than 50% of peak activity) at rest
      redistribution thallium SPECT ("mismatched pattern"); in patient 2, no uptake of
      sestamibi was detected in the dys-synergic area showing a severe irreversible
      defect (less than 50% of peak activity) at rest-redistribution thallium SPECT,
      ("matched pattern"). Forty days after PTCA, contractile recovery as well as
      normalization of thallium uptake occurred in patient 1, confirming that most of
      the dys-synergic area was viable (hibernating), while neither wall motion nor
      thallium uptake improvement occurred in patient 2, confirming that most of the
      dys-synergic area was not viable (scar). We conclude that sestamibi retention in
      the dys-synergic area after selective intracoronary administration correctly
      identified viable and scarred myocardium. The potential diagnostic value of
      intracoronary sestamibi at the time of coronary angiography deserves to be
      validated as a possible alternative to other current procedures for detecting
      hibernating myocardium.

PMID- 9195854
TI  - Separation and analysis of peptides and proteins.

PMID- 9195855
TI  - Forensic science.

PMID- 9195856
TI  - Pharmaceuticals and related drugs.

PMID- 9195857
TI  - Clinical chemistry.

PMID- 9195859
TI  - Industrial hygiene.

PMID- 9195858
TI  - Environmental analysis.

PMID- 9195860
TI  - Body core temperature of rats subjected to daily exercise limited to a fixed
      time.
AB  - Several timed daily environmental cues alter the pattern of nycthemeral
      variations in body core temperature in rodents. The present study investigated
      the effect of timed exercise on variations of daily body core temperature. Male
      rats were housed in cages with a running wheel at an ambient temperature of 24
      degrees C with a 12:12 h light/dark cycle. Timed daily exercise rats (TEX) were
      allowed access to the wheel for 6 h in the last half of the dark phase, freely
      exercising rats (FEX) could run at any time, and sedentary rats (NEX) were not
      allowed to run. After a 3-week exercise period, all animals were denied access to
      the wheel. The intraabdominal temperatures (Tab) and spontaneous activities of
      rats were measured for 6 days after the exercise period. The Tab values of the
      TEX rats were significantly higher than those of the other two groups only in the
      last half of the dark phase, while Tab in the FEX and NEX rats showed no
      significant difference. The specific Tab changes in the TEX rats lasted for 2
      days after the exercise period. Spontaneous activity levels were higher in the
      TEX rats than the FEX and NEX rats in the last half of the dark phase for 1 day
      after the exercise period. The results suggest that daily exercised limited to a
      fixed time per day modifies nycthemeral variations of body core temperature in
      rats so that the temperature increases during the period when the animals had
      previously exercised. Such a rise in body core temperature is partly attributed
      to an increase in the spontaneous activity level.

PMID- 9195861
TI  - Convective and radiative heat transfer coefficients for individual human body
      segments.
AB  - Human thermal physiological and comfort models will soon be able to simulate both
      transient and spatial inhomogeneities in the thermal environment. With this
      increasing detail comes the need for anatomically specific convective and
      radiative heat transfer coefficients for the human body. The present study used
      an articulated thermal manikin with 16 body segments (head, chest, back, upper
      arms, forearms, hands, pelvis, upper legs, lower legs, feet) to generate
      radiative heat transfer coefficients as well as natural- and forced-mode
      convective coefficients. The tests were conducted across a range of wind speeds
      from still air to 5.0 m/s, representing atmospheric conditions typical of both
      indoors and outdoors. Both standing and seated postures were investigated, as
      were eight different wind azimuth angles. The radiative heat transfer coefficient
      measured for the whole-body was 4.5 W/m2 per K for both the seated and standing
      cases, closely matching the generally accepted whole-body value of 4.7 W/m2 per
      K. Similarly, the whole-body natural convection coefficient for the manikin fell
      within the mid-range of previously published values at 3.4 and 3.3 W/m2 per K
      when standing and seated respectively. In the forced convective regime, heat
      transfer coefficients were higher for hands, feet and peripheral limbs compared
      to the central torso region. Wind direction had little effect on convective heat
      transfers from individual body segments. A general-purpose forced convection
      equation suitable for application to both seated and standing postures indoors
      was hc = 10.3v0.6 for the whole-body. Similar equations were generated for
      individual body segments in both seated and standing postures.

PMID- 9195862
TI  - Physiological and psychological assessment of sound.
AB  - The psycho-physiological effects of several sound stimulations were investigated
      to evaluate the relationship between a psychological parameter, such as
      subjective perception, and a physiological parameter, such as the heart rate
      variability (HRV). Eight female students aged 21-22 years old were tested.
      Electrocardiogram (ECG) and the movement of the chest-wall for estimating
      respiratory rate were recorded during three different sound stimulations; (1)
      music provided by a synethesizer (condition A); (2) birds twitters (condition B);
      and (3) mechanical sounds (condition C). The percentage power of the low
      frequency (LF; 0.05 < or = 0.15 Hz) and high-frequency (HF; 0.15 < or = 0.40 Hz)
      components in the HRV (LF%, HF%) were assessed by a frequency analysis of time
      series data for 5 min obtained from R-R intervals in the ECG. Quantitative
      assessment of subjective perception was also described by a visual analog scale
      (VAS). The HF% and VAS value for comfort in C were significantly lower than in
      either A and/or B. The respiratory rate and VAS value for awakening in C were
      significantly higher than in A and/or B. There was a significant correlation
      between the HF% and the value of the VAS, and between the respiratory rate and
      the value of the VAS. These results indicate that mechanical sounds similar to C
      inhibit the para-sympathetic nervous system and promote a feeling that is
      unpleasant but alert, also suggesting that the HRV reflects subjective
      perception.

PMID- 9195863
TI  - Indoor/outdoor concentrations of ozone and peroxyacetyl nitrate (PAN).
AB  - Photochemical pollutants such as ozone and peroxyacetyl nitrate (PAN) could
      adversely affect human health, especially with relation to effects on lung
      function. For a realistic assessment of ambient concentrations, both outdoor and
      indoor measurements of ozone and PAN are required, because people stay indoors
      for most of the time. Indoor/outdoor concentration ratios, indoor half-life times
      and indoor chemistry including physicochemical reactions on surfaces are quite
      well known for ozone, but not for PAN. While ozone is removed very rapidly mainly
      by heterogeneous reactions on surfaces or by gasphase reactions with e.g. carpet
      emissions, no such processes are known for PAN at present. The main removal
      process for PAN is thermal decay. Indoor concentrations of ozone and PAN can be a
      significant fraction of those outdoors highly depending on the ventilation
      pattern. Our measurements in various kinds of non-air-conditioned rooms show
      maximal indoor concentrations between 80 and 100% of those outdoors for ozone and
      PAN, respectively. Average indoor/outdoor ratios were calculated of 0.5 for ozone
      and between 0.7 and 0.9 for PAN. The half-life times ranged between only a few
      minutes for ozone and 0.5 to 1 h for PAN.

PMID- 9195864
TI  - Improved indicators of cell membrane potential that use fluorescence resonance
      energy transfer.
AB  - BACKGROUND: Fluorescence detection of cell membrane potentials is an important
      technique in neurobiology, cell physiology and pharmaceutical screening, but
      traditional one-fluorophore indicators either respond too slowly or have limited
      sensitivity. Recently, we introduced two-component sensors based on the transfer
      of fluorescence resonance energy from fluorescent lectins bound on one side of
      the plasma membrane to highly fluorescent oxonol acceptors that electrophorese
      from one face of the membrane to the other in response to membrane potential.
      RESULTS: We have found that fluorescent lectins can often be advantageously
      replaced in such sensors by fluorescently labeled phospholipids. A
      coumarinlabeled phosphatidylethanolamine donor and a bis(1,3-dihexyl-2
      thiobarbiturate)trimethineoxonol acceptor gave the largest sensitivity of
      fluorescence ratio (>50% per 100 mV) ever reported. The response was also speeded
      several-fold by lengthening the mobile dye to the pentamethineoxonol analog, the
      <0.4 ms time constant of which was shorter than action potential durations.
      Photodynamic damage due to singlet oxygen was reduced by administering a natural
      carotenoid, astaxanthin. CONCLUSIONS: Voltage-sensitive fluorescence resonance
      energy transfer already gives record-setting performance on single cells and will
      continue to be rationally improvable.

PMID- 9195865
TI  - Stevastelins, a novel group of immunosuppressants, inhibit dual-specificity
      protein phosphatases.
AB  - BACKGROUND: Since the molecular target of the immunosuppressive reagents FK506
      and cyclosporin A was revealed to be protein phosphatase PP2B (calcineurin), many
      researchers have been screening the protein phosphatase inhibitors from microbial
      metabolites to develop new immunosuppressive reagents. We isolated stevastelin B,
      which is composed of valine, threonine, serine and 3,5-dihydroxy-2,4-dimethyl
      stearic acid, and stevastelin A, which is a sulphonylated derivative of
      stevastelin B. To understand the action mechanism of stevastelins A and B, we
      synthesized a series of stevastelin derivatives and investigated their structure
      activity relationships. RESULTS: A series of stevastelin derivatives have been
      systematically synthesized. Stevastelin B inhibited gene expression that is
      dependent on interleukin-2 (IL-2) or IL-6 promoters in situ, but it had no
      inhibitory activity against any protein phosphatases in vitro. In contrast,
      stevastelin A, which is a sulphonylated derivative of stevastelin B, inhibited
      the phosphatase activity of a dual-specificity phosphatase, VH1-related human
      protein (VHR), in vitro, but it had no inhibitory activity against gene
      expression or cell-cycle progression in situ. CONCLUSIONS: Stevastelin B is a
      novel immunosuppressant. It inhibited IL-2 or IL-6 dependent gene expression but
      did not inhibit the phosphatase activity of calcineurin. The structure-activity
      relationships show that the acidic functional group on the threonine residue and
      the stearic acid moiety in the stevastelin molecule are important for inhibitory
      effects on the dephosphorylation activity of VHR in vitro. Stevastelin B might be
      sulphonylated or phosphorylated after incorporation into the target cell, and
      then it interacts with protein tyrosine phosphatases and regulates cell-cycle
      progression.

PMID- 9195866
TI  - Understanding enzymic catalysis: the importance of short, strong hydrogen bonds.
AB  - We have proposed previously that short, strong hydrogen bonds exist in enzyme
      active sites and that they are important in explaining enzymic rate enhancements.
      Here, we defend this proposal and provide evidence for likely changes of hydrogen
      bond strengths during enzymic catalysis.

PMID- 9195867
TI  - Structure-based design and combinatorial chemistry yield low nanomolar inhibitors
      of cathepsin D.
AB  - BACKGROUND: The identification of potent small molecule ligands to receptors and
      enzymes is one of the major goals of chemical and biological research. Two
      powerful new tools that can be used in these efforts are combinatorial chemistry
      and structure-based design. Here we address how to join these methods in a design
      protocol that produces libraries of compounds that are directed against specific
      macromolecular targets. The aspartyl class of proteases, which is involved in
      numerous biological processes, was chosen to demonstrate this effective
      procedure. RESULTS: Using cathepsin D, a prototypical aspartyl protease, a number
      of low nanomolar inhibitors were rapidly identified. Although cathepsin D is
      implicated in a number of therapeutically relevant processes, potent nonpeptide
      inhibitors have not been reported previously. The libraries, synthesized on solid
      support, displayed nonpeptide functionality about the (hydroxyethyl)amine
      isostere. The (hydroxyethyl)amine isostere, which targets the aspartyl protease
      class, is a stable mimetic of the tetrahedral intermediate of amide hydrolysis.
      Structure-based design, using the crystal structure of cathepsin D complexed with
      the peptide-based natural product pepstatin, was used to select the building
      blocks for the library synthesis. The library yielded a 'hit rate' of 6-7% at 1
      microM inhibitor concentrations, with the most potent compound having a Ki value
      of 73 nM. More potent, nonpeptide inhibitors (Ki = 9-15 nM) of cathepsin D were
      rapidly identified by synthesizing and screening a small second generation
      library. CONCLUSIONS: The success of these studies clearly demonstrates the power
      of coupling the complementary methods of combinatorial chemistry and structure
      based design. We anticipate that the general approaches described here will be
      successful for other members of the aspartyl protease class and for many other
      enzyme classes.

PMID- 9195869
TI  - Molecular recognition at the thrombin active site: structure-based design and
      synthesis of potent and selective thrombin inhibitors and the X-ray crystal
      structures of two thrombin-inhibitor complexes.
AB  - BACKGROUND: The serine protease thrombin is central in the processes of
      hemostasis and thrombosis. To be useful, thrombin inhibitors should combine
      potency towards thrombin with selectivity towards other related enzymes such as
      trypsin. We previously reported the structure-based design of thrombin inhibitors
      with rigid, bicyclic core structures. These compounds were highly active towards
      thrombin, but showed only modest selectivity. RESULTS: Here, we describe the
      rational design of selective thrombin inhibitors starting from the X-ray crystal
      structure of the complex between the previously generated lead molecule and
      thrombin. The lead molecule bound with a Ki value of 90nM and a selectivity of
      7.8 for thrombin over trypsin. Our design led to inhibitors with improved
      activity and greatly enhanced selectivity. The binding mode for two of the new
      inhibitors was determined by X-ray crystallography of their complexes with
      thrombin. The results confirmed the structures predicted by molecular modeling
      and, together with the binding assays, provided profound insight into molecular
      recognition phenomena at the thrombin active site. CONCLUSIONS: A novel class of
      nonpeptidic, selective thrombin inhibitors has resulted from structure-based
      design and subsequent improvement of the initial lead molecule. These compounds,
      which are preorganized for binding to thrombin through a rigid, bicyclic or
      tricyclic central core, could aid in the development of new antithrombotic drugs.
      Correlative binding and X-ray structural studies within a series of related,
      highly preorganized inhibitors, which all prefer similar modes of association to
      thrombin, generate detailed information on the strength of individual
      intermolecular bonding interactions and their contribution to the overall free
      energy of complexation.

PMID- 9195870
TI  - Pyranosyl-RNA: chiroselective self-assembly of base sequences by ligative
      oligomerization of tetranucleotide-2',3'-cyclophosphates (with a commentary
      concerning the origin of biomolecular homochirality).
AB  - BACKGROUND: Why did Nature choose furanosyl-RNA and not pyranosyl-RNA as her
      molecular genetic system? An experimental approach to this problem is the
      systematic comparison of the two isomeric oligonucleotide systems with respect to
      the chemical properties that are fundamental to the biological role of RNA, such
      as base pairing and nonenzymic replication. Pyranosyl-RNA has been found to be
      not only a stronger, but also a more selective pairing system than natural RNA;
      both form hairpin structures with comparable ease. Base sequences of pyranosyl
      RNA can be copied by template-controlled replicative ligation of short activated
      oligomers (e.g. tetramer-2',3'-cyclophosphates) under mild and potentially
      natural conditions. The copying proceeds with high regioselectivity as well as
      chiroselectivity: homochiral template sequences mediate the formation of the
      correct (4'-->2')-phosphodiester junction between homochiral tetramer units
      provided they have the same sense of chirality as the template. How could
      homochiral template sequences assemble themselves in the first place? RESULTS:
      Higher oligomers of pyranosyl-RNA can self-assemble in dilute solutions under
      mild conditions by ligative oligomerization of tetramer-2',3'-cyclophosphates
      containing hemi self-complementary base sequences. The only side reaction that
      effectively competes with ligation is hydrolytic deactivation of 2',3'
      cyclophosphate end groups. The ligation reaction is highly chiroselective; it is
      slower by at least two orders of magnitude when one of the (D)-ribopyranosyl
      units of a homochiral (D)-tetramer-2',3'-cyclophosphate is replaced by a
      corresponding (L)-unit, except when the (L)-unit is at the 4' end of the tetramer
      and carries a purine, when the oligomerization rate can be approximately 10% of
      that shown for a homochiral isomer. The oligomerization of homochiral tetramers
      is not, or only weakly, inhibited by the presence of the non-oligomerizing
      diastereomers. CONCLUSIONS: Available data on the chiroselective self-directed
      oligomerization of tetramer-2',3'-cyclophosphates allow us to extrapolate that
      sets of tetramers with different but mutually fitting base sequences can be
      expected to co-oligomerize stochastically and generate sequence libraries
      consisting of predominantly homochiral (D)- and (L)-oligomers, starting from the
      racemic mixture of tetramers containing all possible diastereomers. Such a
      capability of an oligonucleotide system deserves special attention in the context
      of the problem of the origin of biomolecular homochirality: breaking molecular
      mirror symmetry by de-racemization is an intrinsic property of such a system
      whenever the constitutional complexity of the products of co-oligomerization
      exceeds a critical level.

PMID- 9195871
TI  - Getting it together: signal transduction in G-protein coupled receptors by
      association of receptor domains.
AB  - The mechanism of signal transduction by G-protein coupled receptors is unknown.
      Here, we propose that these receptors signal in a way that is qualitatively
      similar to that seen in the chemokine and endocrine hormone receptor families;
      the signal occurs when two domains of the receptor are brought together, although
      this is not the only requirement for signaling.

PMID- 9195872
TI  - In vitro selection of a viomycin-binding RNA pseudoknot.
AB  - BACKGROUND: The peptide antibiotic viomycin inhibits ribosomal protein synthesis,
      group I intron self-splicing and self-cleavage of the human hepatitis delta virus
      ribozyme. To understand the molecular basis of RNA binding and recognition by
      viomycin, we isolated a variety of novel viomycin-binding RNA molecules using in
      vitro selection. RESULTS: More than 90% of the selected RNA molecules shared one
      continuous highly conserved region of 14 nucleotides. Mutational analyses,
      structural probing, together with footprinting experiments by chemical
      modification, and Pb2+-induced cleavage showed that this conserved sequence
      harbours the antibiotic-binding site and forms a stem-loop structure. Moreover,
      the loop is engaged in a long-range interaction forming a pseudoknot.
      CONCLUSIONS: A comparison between the novel viomycin-binding motif and the
      natural RNA target sites for viomycin showed that all these segments form a
      pseudoknot at the antibiotic-binding site. We therefore conclude that this
      peptide antibiotic has a strong selectivity for particular RNA pseudoknots.

PMID- 9195873
TI  - Long-range oxidation of guanine by Ru(III) in duplex DNA.
AB  - BACKGROUND: Theoretical and experimental studies have demonstrated that 5'-GG-3'
      sequences in DNA are 'hot spots' for oxidative damage, but few studies have
      definitively addressed whether oxidative damage to DNA may arise from a distance
      via long-range charge migration. Towards this end, we have prepared tethered
      ruthenium (Ru)-oligonucleotide duplexes and used a flash-quench strategy to
      demonstrate long-range charge transport through the DNA double helix. RESULTS:
      DNA assemblies containing a tethered Ru(II) intercalator have been synthesized.
      Ru(III), generated in situ in the presence of externally bound electron-transfer
      quenchers, promotes base damage selectively at the 5'-G of a 5'-GG-3' doublet
      located approximately 37 A from the binding site of the oxidant. In the absence
      of a guanine doublet, oxidative damage occurs equally at all guanine bases in the
      strand. Oxidative damage is also observed at long range for guanine in a G.A
      mismatch but not in a G.T mismatch. CONCLUSIONS: The present study expands the
      scope of long-range electron-transfer chemistry in terms of experiments,
      applications, and possible reactions within the cell. Here we demonstrate
      oxidative damage to DNA occurring with a high quantum yield over a distance of
      approximately 37using a ground-state oxidant. These results point to the
      equilibration of the radical across the DNA duplex to the sites of lowest energy.
      In addition, this charge migration is sensitive to the intervening pi-stack
      formed by DNA base pairs and hence may be useful for the detection of mismatches.

PMID- 9195874
TI  - Identification of intermediates in the catalytic cycle of chloroperoxidase.
AB  - BACKGROUND: Chloroperoxidase (CPO) is the most versatile of the hemethiolate
      proteins, catalyzing the chlorination of activated C-H bonds and reactions
      reminiscent of peroxidase, catalase, and cytochrome P450. Despite 30 years of
      continuous efforts, no intermediates of the enzyme's catalytic cycle have been
      identified except for compound I. Thus, in the absence of conclusive evidence it
      is generally believed that the halogenation of substrates proceeds by means of
      'free HOCI' in solution. RESULTS: The pH profile of chloroperoxidase from
      Caldariomyces fumago revealed a new active-site complex that can be detected only
      at pH 4.4. According to ultra-violet (UV) spectroscopy, and by comparison with
      suitable enzyme models, this intermediate is the HOCl adduct of the iron(III)
      protoporphyrin(IX). Inactivation of chloroperoxidase by diethyl pyrocarbonate,
      which interrupts the proton shuttle by modification of the distal histidine, led
      to the formation of the -OCl adduct of the iron complex, which was identified by
      comparison with a corresponding active site analogue. CONCLUSIONS: The
      availability of enzyme models of heme-thiolate proteins allowed the
      identification by UV spectroscopy of both the -OCl adduct and the HOCl adduct of
      the iron(III) protoporphyrin(IX) of chloroperoxidase. The existence of these
      previously elusive intermediates suggests that the chlorination catalyzed by CPO,
      and its corresponding active site analogue, proceeds by Cl+ transfer from the
      HOCl adduct to the substrate bound in the distal pocket of the enzyme.

PMID- 9195875
TI  - Kinetics and mechanism of amyloid formation by the prion protein H1 peptide as
      determined by time-dependent ESR.
AB  - BACKGROUND: Peptides derived from three of four putative alpha-helical regions of
      the prion protein (PrP) form amyloid in solution. These peptides serve as models
      for amyloidogenesis and for understanding the alpha helix -->beta strand
      conformational change that is responsible for the development of disease. Kinetic
      studies of amyloid formation usually rely on the detection of fibrils. No study
      has yet explored the rate of monomer peptide uptake or the presence of
      nonfibrillar intermediate species. We present a new electron spin resonance (ESR)
      method for probing the kinetics of amyloid formation. A spin label was covalently
      attached to a highly amyloidogenic peptide and kinetic trials were monitored by
      ESR. RESULTS: Electron microscopy shows that the spin-labeled peptide forms
      amyloid, and ESR reveals the kinetic decay of free peptide monomer during amyloid
      formation. The combination of electron microscopy and ESR suggests that there are
      three kinetically relevant species: monomer peptide, amyloid and amorphous
      aggregate (peptide aggregates devoid of fibrils or other structures with long
      range order). A rather surprising result is that amyloid formation requires the
      presence of this amorphous aggregate. This is particularly interesting because
      PrPSc, the form of PrP associated with scrapie, is often found as an aggregate
      and amyloid formation is not a necessary component of prion replication or
      pathogenesis. CONCLUSIONS: Kinetic analysis of the time-dependent data suggests a
      model whereby the amorphous aggregate has a previously unsuspected dual role: it
      releases monomer into solution and also provides initiation sites for fibril
      growth. These findings suggest that the beta-sheet-rich PrPSc may be stabilized
      by aggregation.

PMID- 9195876
TI  - A model of the structure of HOO-Co.bleomycin bound to d(CCAGTACTGG): recognition
      at the d(GpT) site and implications for double-stranded DNA cleavage.
AB  - BACKGROUND: The bleomycins (BLMs) are a family of natural products used
      clinically as antitumor agents. In the presence of their required cofactors, iron
      and oxygen, BLMs bind to and mediate single-stranded and double-stranded DNA
      cleavage. Recently, two dimensional nuclear magnetic resonance (2D NMR)
      spectroscopic studies and molecular modeling have provided a picture of how the
      hydroperoxide form of cobalt BLM A2 (HOO-CoBLM), an analog of 'activated' iron
      BLM (HOO-FeBLM), binds to a d(GpC) motif and of the basis for both sequence
      specificity and chemical specificity of DNA cleavage. RESULTS: The solution
      structure of HOO-CoBLM bound to d(CCAGTACTGG) containing a 'hot spot' for double
      stranded DNA cleavage at T5 and T15 is reported using constraints from 2D NMR
      spectroscopy. The mode of binding and basis for sequence specificity and chemical
      specificity of cleavage is almost identical to that of a d(GpC) motif. This
      structure has allowed formulation of a structural model for how a single molecule
      of FeBLM can mediate a double-stranded DNA cleavage event without dissociation
      from the DNA. CONCLUSIONS: The structural similarity of HOO-CoBLM bound to d(GpT)
      in d(CCAGTACTGG) compared to a d(GpC) motif suggests a general paradigm for the
      binding of HOO-CoBLM to DNA and, by analogy, for the binding of the biological
      significant entity HOO-FeBLM.

PMID- 9195877
TI  - Viral RNA export.
AB  - Viruses can express intron-containing and intronless mRNAs, which are exported by
      alternative pathways. The study of the nuclear export of these unconventional
      mRNAs can provide key insights into the normal process of nuclear export and the
      alternative pathways provide an attractive target for the development of specific
      antiviral therapies.

PMID- 9195879
TI  - How do DNA repair proteins locate damaged bases in the genome?
AB  - The genome is susceptible to the attack of reactive species that chemically
      modify the bases of DNA. If genetic information is to be transmitted faithfully
      to successive generations, it is essential that the genome be repaired. All
      organisms express proteins specifically dedicated to this task. But how do these
      proteins find the aberrant bases amongst the enormous number of normal ones?

PMID- 9195880
TI  - The structure of a calmodulin mutant with a deletion in the central helix:
      implications for molecular recognition and protein binding.
AB  - BACKGROUND: Calmodulin (CaM) is the major calcium-dependent regulator of a large
      variety of important intracellular processes in eukaryotes. The structure of CaM
      consists of two globular calcium-binding domains joined by a central 28-residue
      alpha helix. This linker helix has been hypothesized to act as a flexible tether
      and is crucial for the binding and activation of numerous target proteins.
      Although the way in which alterations of the central helix modulate the molecular
      recognition mechanism is not known exactly, the relative orientation of the
      globular domains seems to be of great importance. The structural analysis of
      central helix mutants may contribute to a better understanding of how changes in
      the conformation of CaM effect its function. RESULTS: We have determined the
      crystal structure of a calcium-saturated mutant of chicken CaM (mut-2) that lacks
      two residues in the central helix, Thr79 and Asp80, at 1.8 A resolution. The
      mutated shorter central helix is straight, relative to that of the wild-type
      structure. The loss of a partial turn of the central alpha helix causes the C
      terminal domain to rotate 220 degrees around the helix axis, with respect to the
      N-terminal domain. This rotation places the two domains on the same side of the
      central helix, in a cis orientation, rather than in the trans orientation found
      in wild-type structures. CONCLUSIONS: The deletion of two residues in the central
      helix of CaM does not distort or cause a bending of the linker alpha helix. The
      main consequence of the mutation is a change in the relative orientation of the
      two globular calcium-binding domains, causing the hydrophobic patches in these
      domains to be closer and much less accessible to interact with the target
      enzymes. This may explain why this mutant of CaM shows a marked decrease in its
      ability to activate some enzymes while the mutation has little or no effect on
      its ability to activate others.

PMID- 9195881
TI  - A 'specificity' pocket inferred from the crystal structures of the complexes of
      aldose reductase with the pharmaceutically important inhibitors tolrestat and
      sorbinil.
AB  - BACKGROUND: Aldose reductase (AR) is an NADPH-dependent enzyme implicated in long
      term diabetic complications. Buried at the bottom of a deep hydrophobic cleft,
      the NADPH coenzyme is surrounded by the conserved hydrophilic residues of the AR
      active site. The existence of an anionic binding site near the NADP+ has been
      determined from the structures of the complexes of AR with citrate, cacodylate
      and glucose-6-phosphate. The inhibitor zopolrestat binds to this anionic site,
      and in the hydrophobic cleft, after a change of conformation which opens a
      'specificity' pocket. RESULTS: The crystal structures of the porcine AR
      holoenzyme and its complexes with the inhibitors tolrestat and sorbinil have been
      solved; these structures are important as tolrestat and sorbinil are,
      pharmaceutically, the most well-studied AR inhibitors. The active site of the
      holoenzyme was analyzed, and binding of the inhibitors was found to involve two
      contact zones in the active site: first, a recognition region for hydrogen-bond
      acceptors near the coenzyme, with three centers, including the anionic site; and
      second, a hydrophobic contact zone in the active-site cleft, which in the case of
      tolrestat includes the specificity pocket. The conformational change leading to
      the opening of the specificity pocket upon tolrestat binding is different to the
      one seen upon zopolrestat binding; this pocket binds inhibitors that are more
      effective against AR than against aldehyde reductase. CONCLUSIONS: The active
      site of AR adapts itself to bind tightly to different inhibitors; this happens
      both upon binding to the inhibitor's hydrophilic heads, and at the hydrophobic
      and specificity pockets of AR, which can change their shape through different
      conformational changes of the same residues. This flexibility could explain the
      large variety of possible substrates of AR.

PMID- 9195882
TI  - A modulator of rho family G proteins, rhoGDI, binds these G proteins via an
      immunoglobulin-like domain and a flexible N-terminal arm.
AB  - BACKGROUND: The rho family of small G proteins, including rho, rac and cdc42, are
      involved in many cellular processes, including cell transformation by ras and the
      organization of the actin cytoskeleton. Additionally, rac has a role in the
      regulation of phagocyte NADPH oxidase. Guanine nucleotide dissociation inhibitors
      (GDIs) of the rhoGDI family bind to these G proteins and regulate their activity
      by preventing nucleotide dissociation and by controlling their interaction with
      membranes. RESULTS: We report the structure of rhoGDI, determined by a
      combination of X-ray crystallography and NMR spectroscopy. NMR spectroscopy and
      selective proteolysis show that the N-terminal 50-60 residues of rhoGDI are
      flexible and unstructured in solution. The 2.5 A crystal structure of the folded
      core of rhoGDI, comprising residues 59-204, shows it to have an immunoglobulin
      like fold, with an unprecedented insertion of two short beta strands and a 310
      helix. There is an unusual pocket between the beta sheets of the immunoglobulin
      fold which may bind the C-terminal isoprenyl group of rac. NMR spectroscopy shows
      that the N-terminal arm is necessary for binding rac, although it remains largely
      flexible even in the complex. CONCLUSIONS: The rhoGDI structure is notable for
      the existence of both a structured and a highly flexible domain, both of which
      appear to be required for the interaction with rac. The immunoglobulin-like fold
      of the structured domain is unusual for a cytoplasmic protein. The presence of
      equivalent cleavage sites in rhoGDI and the closely related D4/Ly-GDI (rhoGDI-2)
      suggest that proteolytic cleavage between the flexible and structured regions of
      rhoGDI may have a role in the regulation of the activity of members of this
      family. There is no detectable similarity between the structure of rhoGDI and the
      recently reported structure of rabGDI, which performs the same function as rhoGDI
      for the rab family of small G proteins.

PMID- 9195883
TI  - Formylmethanofuran: tetrahydromethanopterin formyltransferase from Methanopyrus
      kandleri - new insights into salt-dependence and thermostability.
AB  - BACKGROUND: Formylmethanofuran: tetrahydromethanopterin formyltransferase (Ftr)
      from the methanogenic Archaeon Methanopyrus kandleri (optimum growth temperature
      98 degrees C) is a hyperthermophilic enzyme that is absolutely dependent on the
      presence of lyotropic salts for activity and thermostability. The enzyme is
      involved in the pathway of carbon dioxide reduction to methane and catalyzes the
      transfer of formyl from formylmethanofuran to tetrahydromethanopterin. RESULTS:
      The crystal structure of Ftr, determined to a resolution of 1:73 AE reveals a
      homotetramer composed essentially of two dimers. Each subunit is subdivided into
      two tightly associated lobes both consisting of a predominantly antiparallel beta
      sheet flanked by alpha helices forming an alpha/beta sandwich structure. The
      approximate location of the active site was detected in a region close to the
      dimer interface. CONCLUSIONS: The adaptation of Ftr against high lyotropic salt
      concentrations is structurally reflected by a large number of negatively charged
      residues and their high local concentration on the surface of the protein. The
      salt-dependent thermostability of Ftr might be explained on a molecular basis by
      ionic interactions at the protein surface, involving both protein and inorganic
      salt ions, and the mainly hydrophobic interactions between the subunits and
      within the core.

PMID- 9195884
TI  - Solution structure of the granular starch binding domain of Aspergillus niger
      glucoamylase bound to beta-cyclodextrin.
AB  - BACKGROUND: Carbohydrate-binding domains are usually small and physically
      separate from the catalytic domains of hydrolytic enzymes. Glucoamylase 1 (G1)
      from Aspergillus niger, an enzyme used widely in the food and brewing industries,
      contains a granular starch binding domain (SBD) which is separated from the
      catalytic domain by a semi-rigid linker. The aim of this study was to determine
      how the SBD binds to starch, and thereby more generally to throw light on the
      role of carbohydrate-binding domains in the hydrolysis of insoluble
      polysaccharides. RESULTS: The solution structure of the SBD of A. niger G1 bound
      to beta-cyclodextrin (betaCD), a cyclic starch analogue, shows that the well
      defined beta-sheet structure seen in the free SBD is maintained in the SBD-betaCD
      complex. The main differences between the free and bound states of the SBD are
      observed in loop regions, in or near the two starch-binding sites. The two
      binding sites, each of which binds one molecule of betaCD, are structurally
      different. Binding site 1 is small and accessible, and its structure changes very
      little upon ligand binding. Site 2 is longer and undergoes a significant
      structural change on binding. Part of this site comprises a flexible loop, which
      appears to allow the SBD to bind to starch strands in a range of orientations.
      CONCLUSIONS: The two starch-binding sites of the SBD probably differ functionally
      as well as structurally; site 1 probably acts as the initial starch recognition
      site, whereas site 2 is involved in specific recognition of appropriate regions
      of starch. The two starch strands are bound at approximately 90 degrees to each
      other. This may be functionally important, as it may force starch strands apart
      thus increasing the hydrolyzable surface, or alternatively it may localize the
      enzyme to noncrystalline (more hydrolyzable) areas of starch. The region of the
      SBD where the linker to the catalytic domain is attached is flexible, allowing
      the catalytic site to access a large surface area of the starch granules.

PMID- 9195885
TI  - Crystal structure of nitrile hydratase reveals a novel iron centre in a novel
      fold.
AB  - BACKGROUND: Nitrile hydratases are unusual metalloenzymes that catalyze the
      hydration of nitriles to their corresponding amides. They are used as
      biocatalysts in acrylamide production, one of the few commercial scale
      bioprocesses, as well as in environmental remediation for the removal of nitriles
      from waste streams. Nitrile hydratases are composed of two subunits, alpha and
      beta, and they contain one iron atom per alphabeta unit. We have determined the
      crystal structure of photoactivated iron-containing nitrile hydratase from
      Rhodococcus sp. R312 to 2.65 A resolution as a first step in the elucidation of
      its catalytic mechanism. RESULTS: The alpha subunit consists of a long N-terminal
      arm and a C-terminal domain that forms a novel fold. This fold can be described
      as a four layered structure, alpha-beta-beta-alpha, with unusual connectivities
      between the beta strands. The beta subunit also contains a long N-terminal
      extension, a helical domain, and a C-terminal domain that folds into a beta roll.
      The two subunits form a tight heterodimer that is the functional unit of the
      enzyme. The active site is located in a cavity at the subunit-subunit interface.
      The iron centre is formed by residues from the alpha subunit only-three cysteine
      thiolates and two mainchain amide nitrogen atoms are ligands. CONCLUSIONS:
      Nitrile hydratases contain a novel iron centre with a structure not previously
      observed in proteins; it resembles a hybrid of the iron centres of heme and Fe-S
      proteins. The low-spin electronic configuration presumably results in part from
      two Fe-amide nitrogen bonds. The structure is consistent with the metal ion
      having a role as a Lewis acid in the catalytic reaction.

PMID- 9195886
TI  - The crystal structures of Sinapis alba myrosinase and a covalent glycosyl-enzyme
      intermediate provide insights into the substrate recognition and active-site
      machinery of an S-glycosidase.
AB  - BACKGROUND: Myrosinase is the enzyme responsible for the hydrolysis of a variety
      of plant anionic 1-thio-beta-D-glucosides called glucosinolates. Myrosinase and
      glucosinolates, which are stored in different tissues of the plant, are mixed
      during mastication generating toxic by-products that are believed to play a role
      in the plant defence system. Whilst O-glycosidases are extremely widespread in
      nature, myrosinase is the only known S-glycosidase. This intriguing enzyme, which
      shows sequence similarities with O-glycosidases, offers the opportunity to
      analyze the similarities and differences between enzymes hydrolyzing S- and O
      glycosidic bonds. RESULTS: The structures of native myrosinase from white mustard
      seed (Sinapis alba) and of a stable glycosyl-enzyme intermediate have been solved
      at 1.6 A resolution. The protein folds into a (beta/alpha)8-barrel structure,
      very similar to that of the cyanogenic beta-glucosidase from white clover. The
      enzyme forms a dimer stabilized by a Zn2+ ion and is heavily glycosylated. At one
      glycosylation site the complete structure of a plant-specific heptasaccharide is
      observed. The myrosinase structure reveals a hydrophobic pocket, ideally situated
      for the binding of the hydrophobic sidechain of glucosinolates, and two arginine
      residues positioned for interaction with the sulphate group of the substrate.
      With the exception of the replacement of the general acid/base glutamate by a
      glutamine residue, the catalytic machinery of myrosinase is identical to that of
      the cyanogenic beta-glucosidase. The structure of the glycosyl-enzyme
      intermediate shows that the sugar ring is bound via an alpha-glycosidic linkage
      to Glu409, the catalytic nucleophile of myrosinase. CONCLUSIONS: The structure of
      myrosinase shows features which illustrate the adaptation of the plant enzyme to
      the dehydrated environment of the seed. The catalytic mechanism of myrosinase is
      explained by the excellent leaving group properties of the substrate aglycons,
      which do not require the assistance of an enzymatic acid catalyst. The
      replacement of the general acid/base glutamate of O-glycosidases by a glutamine
      residue in myrosinase suggests that for hydrolysis of the glycosyl-enzyme, the
      role of this residue is to ensure a precise positioning of a water molecule
      rather than to provide general base assistance.

PMID- 9195887
TI  - Two crystal structures of pectin lyase A from Aspergillus reveal a pH driven
      conformational change and striking divergence in the substrate-binding clefts of
      pectin and pectate lyases.
AB  - BACKGROUND: Microbial pectin and pectate lyases are virulence factors that
      degrade the pectic components of the plant cell wall. The homogalacturan backbone
      of pectin varies in its degree of methylation from the highly methylated and
      relatively hydrophobic form known as pectin, to the fully demethylated and highly
      charged form known as pectate. Methylated and demethylated regions of pectin are
      cleaved by pectin lyase and calcium-dependent pectate lyases, respectively.
      Protein engineering of lyases specific for particular patterns of methylation,
      will yield modified pectins of high value to the food and pharmaceutical
      industries. RESULTS: The crystal structures of pectin lyase A from two strains of
      Aspergillus niger, N400 and 4M-147, have been determined at pH 6.5 (2.4 A
      resolution) and pH 8.5 (1.93 A resolution), respectively. The structures were
      determined by a combination of molecular replacement, multiple isomorphous
      replacement and intercrystal averaging. Pectin lyase A folds into a parallel beta
      helix and shares many of the structural features of pectate lyases, despite no
      more than 17% sequence identity after pairwise structure-based alignment. These
      shared structural features include amino acid stacks and the asparagine ladder.
      However, the differences in the substrate-binding clefts of these two enzymes are
      striking. In pectin lyase A, the cleft is dominated by aromatic residues and is
      enveloped by negative electrostatic potential. In pectate lyases, this cleft is
      rich in charged residues and contains an elongated ribbon of positive potential
      when Ca2+ is bound. The major difference between the two pectin lyase A
      structures from the two strains is in the conformation of the loop formed by
      residues 182-187. These observed differences are due to the different pH values
      of crystallization. CONCLUSIONS: The substrate-binding clefts and catalytic
      machinery of pectin and pectate lyases have diverged significantly. Specificity
      is dictated by both the nature of the protein-carbohydrate interaction and long
      range electrostatic forces. Three potential catalytic residues have been
      identified in pectin lyase, two of these are common to pectate lyases. Pectin
      lyase A does not bind Ca2+ but an arginine residue is found in an equivalent
      position to the Ca2+ ion in pectate lyase, suggesting a similar role in
      catalysis. The activity of pectin lyase A is pH -dependent with an optimum
      activity at pH 5.5. The activity drops above pH 7.0 due to a conformational
      change at the binding cleft, triggered by the proximity of two buried aspartate
      residues.

PMID- 9195888
TI  - Structure of mitochondrial aldehyde dehydrogenase: the genetic component of
      ethanol aversion.
AB  - BACKGROUND: The single genetic factor most strongly correlated with reduced
      alcohol consumption and incidence of alcoholism is a naturally occurring variant
      of mitochondrial aldehyde dehydrogenase (ALDH2). This variant contains a
      glutamate to lysine substitution at position 487 (E487K). The E487K variant of
      ALDH2 is found in approximately 50% of the Asian population, and is associated
      with a phenotypic loss of ALDH2 activity in both heterozygotes and homozygotes.
      ALDH2-deficient individuals exhibit an averse response to ethanol consumption,
      which is probably caused by elevated levels of blood acetaldehyde. The structure
      of ALDH2 is important for the elucidation of its catalytic mechanism, to gain a
      clear understanding of the contribution of ALDH2 to the genetic component of
      alcoholism and for the development of specific ALDH2 inhibitors as potential
      drugs for use in the treatment of alcoholism. RESULTS: The X-ray structure of
      bovine ALDH2 has been solved to 2.65 A in its free form and to 2.75 A in a
      complex with NAD+. The enzyme structure contains three domains; two dinucleotide
      binding domains and a small three-stranded beta-sheet domain, which is involved
      in subunit interactions in this tetrameric enzyme. The E487K mutation occurs in
      this small oligomerization domain and is located at a key interface between
      subunits immediately below the active site of another monomer. The active site of
      ALDH2 is divided into two halves by the nicotinamide ring of NAD+. Adjacent to
      the A-side (Pro-R) of the nicotinamide ring is a cluster of three cysteines
      (Cys301, Cys302 and Cys303) and adjacent to the B-side (Pro-S) are Thr244,
      Glu268, Glu476 and an ordered water molecule bound to Thr244 and Glu476.
      CONCLUSIONS: Although there is a recognizable Rossmann-type fold, the coenzyme
      binding region of ALDH2 binds NAD+ in a manner not seen in other NAD+-binding
      enzymes. The positions of the residues near the nicotinamide ring of NAD+ suggest
      a chemical mechanism whereby Glu268 functions as a general base through a bound
      water molecule. The sidechain amide nitrogen of Asn169 and the peptide nitrogen
      of Cys302 are in position to stabilize the oxyanion present in the tetrahedral
      transition state prior to hydride transfer. The functional importance of residue
      Glu487 now appears to be due to indirect interactions of this residue with the
      substrate-binding site via Arg264 and Arg475.

PMID- 9195889
TI  - Solution structure of a metal-binding site in the major groove of RNA complexed
      with cobalt (III) hexammine.
AB  - BACKGROUND: Solvated metal ions are critical for the proper folding and function
      of RNA. Despite the importance of these ions, the details of specific metal ion
      RNA interactions are poorly understood. The crystal structure of a group I intron
      ribozyme domain characterized several metal-binding sites in the RNA with osmium
      (III) hexammine bound in the major groove. A corresponding method for locating
      and characterizing metal-binding sites of RNA in solution is of obvious interest.
      NMR should be ideal for localizing metal hexammine ions bound to the RNA because
      of the large concentration of protons around the metal center. RESULTS: We have
      solved the solution structure of the P5b stem loop from a group I intron ribozyme
      bound to a cobalt (III) hexammine ion. The location of the ion is precisely
      determined by intermolecular nuclear Overhausser effect cross-peaks between the
      cobalt (III) hexammine protons and both exchangeable and non-exchangeable RNA
      protons in the major groove. The binding site consists of tandem G-U base pairs
      in a sequence of four consecutive G residues ending in a GAAA tetraloop, as
      originally identified in the crystal structure. The edges of the bases in the
      major groove present an electrostatically negative face and a variety of hydrogen
      bond acceptors for the cobalt (III) hexammine ion. The metal ion ligand is bound
      near the guanosine nucleotides of the adjacent G-U base pairs, where it makes
      hydrogen bonds with the N7 and carbonyl groups of both guanines. The carbonyl
      groups of the uracil residues add to the negative surface of the binding pocket,
      but do not form hydrogen bonds with the hexammine. Additional hydrogen bonds form
      with other guanine residues of the GGGG sequence. The structure of the binding
      site does not change significantly on binding the cobalt (III) hexammine. The
      structure of the complex in solution is very similar to the structure in the
      crystal. CONCLUSIONS: The structure presents a picture of how tandem G-U base
      pairs bind and position metal ions within the RNA major groove. The binding site
      is performed in the absence of metal ions, and presents a negative pocket in the
      major groove with a variety of hydrogen-bond acceptors. Because G-U base pairs
      are such a common motif in RNA sequences, it is possible that this RNA-metal ion
      interaction is critical in forming large complex RNA structures such as those
      found in the ribosome and self-splicing introns. This structure was determined
      using cobalt (III) hexammine as an analog for hexahydrated magnesium, a technique
      that may be applicable to other RNA sequences. Metal hexammines may prove to be
      useful general probes for locating RNA metal ion binding sites in solution.

PMID- 9195890
TI  - Amyloid fibril formation and protein misassembly: a structural quest for insights
      into amyloid and prion diseases.
AB  - The assembly and misassembly of normally soluble proteins into fibrilar
      structures is thought to be a causative agent in a variety of human amyloid and
      prion diseases. Structural and mechanistic studies of this process are beginning
      to elucidate the conformational changes required for the conversion of a normally
      soluble and functional protein into a defined quaternary structure.

PMID- 9195892
TI  - Magnesium protects against cocaine-induced hemorrhagic stroke in a rat model: a
      31P-NMR in-vivo study.
AB  - In-vivo 31P-nuclear magnetic resonance (NMR) studies were undertaken with
      anesthetized rats to determine: a. whether systemic administration of MgCl2 could
      protect animals against cocaine-induced hemorrhagic stroke, and b. whether a
      relationship exists between basal levels of brain intracellular free magnesium
      ions ([Mg2+]i), phosphometabolites, and stroke risk. Repeat 31P-NMR spectra were
      obtained at various intervals of time (3-120 min, or up until death) after
      administration of cocaine (5 + 30 mg/kg). Ion selective electrodes were used to
      measure plasma Mg2+, K+, Na+ and Ca2+. Forty percent of animals died in the
      absence of Mg2+ infusion following high dosage of cocaine. Only 13% died with
      cocaine following Mg2+ infusion (p <0.005). In the Mg2+-protected animals,
      neither brain [Mg2+]i,intracellular pH (pHi), [phosphocreatine-PCr]/[ATP], nor
      brain [inorganic phosphate-Pi]/[ATP] fell when toxic and lethal doses of cocaine
      were given. Low basal brain [Mg2+]i (275 +/- 24 vs. 466 +/- 35 microM, p <0.01)
      and low basal brain [PCr] (3.36 +/- 0.35 vs. 4.26 +/- 0.24 mM, p <0.01) were
      found to be associated with a 3-fold increased incidence of stroke. A positive
      correlation (r = 0.31, p <0.03) between brain [Mg2+]1 and [PCr]/[ATP] was found.
      It is possible that both brain [Mg2+]i and [PCr] may be useful as important
      predictors of susceptibility to cocaine-induced hemorrhagic stroke.

PMID- 9195893
TI  - Modulation of ara-C induced apoptosis in leukemia by the PKC activator bryostatin
      1.
AB  - Modulation of ara-C-induced apoptosis in human leukemia cells by the macrocyclic
      lactone PKC activator bryostatin 1 occurs at multiple levels, and involves a
      variety of oncogenes and signalling pathways. Under some circumstances,
      bryostatin 1 may lead to enhanced conversion of ara-C to its lethal metabolite,
      ara-CTP. However, bryostatin 1 is able to potentiate ara-C-mediated cytotoxicity
      in the absence of metabolic perturbations, presumably by modulating the cell
      death pathway itself. For example, chronic exposure of cells to bryostatin 1
      leads to PKC down-regulation, which may alter the balance between survival (e.g.,
      ERK) versus stress (e.g., SAPK/JNK)-related pathways. The ability of bryostatin 1
      to enhance ara-C-mediated apoptosis is inversely related to its capacity to
      induce leukemic cell maturation and may involve the failure to down-regulate
      expression of the cell cycle progression-related proto-oncogene, c-myc. Finally,
      recent evidence suggests that bryostatin 1 may act, through modification of Bcl-2
      phosphorylation status, at a distal site in the cell death pathway. These studies
      could provide a paradigm important for understanding the mechanism(s) by which
      agents acting through signal transduction pathways modulate cytotoxic drug
      induced cell death

PMID- 9195894
TI  - An improved method for Southwestern blotting.
AB  - We have developed a modified Southwestern blotting technique which utilizes broad
      spectrum protease inhibitors during nuclear protein extraction and a procedure
      for radiolabelling an oligonucleotide probe to a high specific activity. These
      modifications have resulted in minimal protein degradation during nuclear protein
      isolation and have permitted room temperature hybridizations, improving both the
      facility and sensitivity of the standard Southwestern assay. This technique was
      used in our laboratory to visualize NFAT-1 consensus sequence binding proteins in
      nuclear extracts of human promyelocytic HL-60 cells.

PMID- 9195895
TI  - The comparative biology of pulmonary intravascular macrophages.
AB  - Pulmonary intravascular macrophages are an important part of the mononuclear
      phagocyte system in some species of mammals, mainly sheep and other ruminants,
      pigs, and horses. These cells phagocytize foreign particles, cell debris and
      pathogens that pass through the pulmonary circulation. Species with intravascular
      macrophages localize intravenously injected tracer particles and bacteria
      predominantly in the lung rather than the liver, and exhibit pulmonary
      hypertension when these cells are activated. Both in vivo and in vitro studies
      show that pulmonary intravascular macrophages have distinct secretory and immune
      capabilities. Consequently, the pulmonary intravascular macrophages play an
      important role in pulmonary inflammation in species that have them

PMID- 9195897
TI  - Function and inhibition of intracellular calcium-independent phospholipase A2.

PMID- 9195898
TI  - Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein kinase
      cascade.
AB  - The calmodulin-dependent kinase (CaM-K) cascade, a Ca2+-triggered system
      involving phosphorylation and activation of CaM-KI and CaM-KIV by CaM kinase
      kinase (CaM-KK), regulates transcription through direct phosphorylation of
      transcription factors such as cAMP response element-binding protein. We have
      shown previously that activated CaM-KIV can activate the mitogen-activated
      protein kinases (Enslen, H., Tokumitsu, H., Stork, P. J. S., Davis, R. J., and
      Soderling, T. R. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 10803-10808), and the
      present paper describes a novel regulatory cross-talk between cAMP kinase (PKA)
      and CaM-KK. PKA gave rapid phosphorylation in vitro and in cells of recombinant
      CaM-KK, resulting in 50-75% inhibition of CaM-KK activity, part of which was due
      to suppression of CaM-binding by phosphorylation of Ser458 in the CaM-binding
      domain. However, the Ser458 --> Ala mutant, or a truncation mutant in which the
      CaM-binding and autoinhibitory domains were deleted, was still partially
      suppressed by PKA-mediated phosphorylation. The second inhibitory site was
      identified as Thr108 by site-specific mutagenesis. Treatments of COS-7, PC12,
      hippocampal, or Jurkat cells with the PKA activators forskolin or isoproterenol
      gave 30-90% inhibition of either endogenous or transfected CaM-KK and/or CaM-KIV
      activities. These results demonstrate that the CaM kinase cascade is negatively
      regulated in cells by the cAMP/PKA pathway.

PMID- 9195899
TI  - Molecular cloning of SKAP55, a novel protein that associates with the protein
      tyrosine kinase p59fyn in human T-lymphocytes.
AB  - In human T-lymphocytes the Src family protein tyrosine kinase p59(fyn) associates
      with three phosphoproteins of 43, 55, and 85 kDa (pp43, pp55, and pp85).
      Employing a GST-Fyn-Src homology 2 (SH2) domain fusion protein pp55 was purified
      from lysates of Jurkat T-cells. Molecular cloning of the pp55 cDNA reveals that
      the pp55 gene codes for a so far nondescribed polypeptide of 359 amino acids that
      comprises a pleckstrin homology domain, a C-terminal SH3 domain, as well as
      several potential tyrosine phosphorylation sites, among which one fulfills the
      criteria to bind Src-like SH2 domains with high affinity. Consistent with this
      observation, pp55 selectively binds to isolated SH2 domains of Lck, Lyn, Src, and
      Fyn but not to the SH2 domains of ZAP70, Syk, Shc, SLP-76, Grb2,
      phosphatidylinositol 3-kinase, and c-abl in vitro. Based on these properties the
      protein was termed SKAP55 (src kinase-associated phosphoprotein of 55 kDa).
      Northern blot analysis shows that SKAP55 mRNA is preferentially expressed in
      lymphatic tissues. SKAP55 is detected in resting human T-lymphocytes as a
      constitutively tyrosine phosphorylated protein that selectively interacts with
      p59(fyn). These data suggest that SKAP55 represents a novel adaptor protein
      likely involved in Fyn-mediated signaling in human T-lymphocytes.

PMID- 9195900
TI  - Physical and functional interactions of Doc2 and Munc13 in Ca2+-dependent
      exocytotic machinery.
AB  - Doc2 has two C2 domains that interact with Ca2+ and phospholipid. Munc13 has two
      C2 domains and one C1 domain that interacts with phorbol ester or diacylglycerol
      (DAG) and phospholipid. Both Doc2 and Munc13 are implicated in Ca2+-dependent
      neurotransmitter release, but their modes of action still remain unclear. We show
      here that Doc2 interacts with Munc13 both in a cell-free system and in intact
      PC12 cells during the high K+-induced Ca2+-dependent exocytosis. The Doc2-Munc13
      interactions are stimulated by phorbol ester through the C1 domain of Munc13.
      Overexpression of the Doc2-interacting domain of Munc13 reduces the Ca2+
      dependent exocytosis from PC12 cells, and co-expression with Doc2 suppresses this
      reduction. These results, together with the earlier findings that secretagogues
      produce DAG and elevate cytoplasmic Ca2+, suggest that the DAG-induced Doc2
      Munc13 interactions play an important role in Ca2+-dependent exocytotic
      machinery.

PMID- 9195901
TI  - Intracellular generation and accumulation of amyloid beta-peptide terminating at
      amino acid 42.
AB  - Amyloid beta-peptide (Abeta) is known to accumulate in senile plaques of
      Alzheimer's disease (AD) patients and is now widely believed to play a major role
      in the disease. Two populations of peptides occur terminating either at amino
      acid 40 or at amino acid 42 (Abeta1-40 and Abeta1-42). Alternative N-terminal
      cleavages produce additional heterogeneity (Abetax-40 and Abetax-42). Peptides
      terminating at amino acid 42 are believed to be the major player in sporadic AD
      as well as familial AD (FAD). Whereas the cellular mechanism for the generation
      of Abeta terminating at amino acid 40 is well understood, very little is known
      about the cleavage of Abeta after amino acid 42. By using two independent methods
      we demonstrate intracellular Abeta1-42 as well as Abetax-42 but less Abetax-40
      and Abeta1-40 in kidney 293 cells stably transfected with wild type beta-amyloid
      precursor protein (betaAPP) or the FAD-associated Val/Gly mutation. Moreover,
      retention of betaAPP within the endoplasmic reticulum (ER) by treatment with
      brefeldin A does not block the cleavage at amino acid 42 but results in an
      increased production of all species of Abeta terminating at amino acid 42. This
      indicates that the cleavage after amino acid 42 can occur within the ER.
      Treatment of cells with monensin, which blocks transport of (betaAPP) within the
      Golgi causes a marked accumulation of intracellular Abetax-42 and Abetax-40.
      Therefore these experiments indicate that the gamma-secretase cleavage of Abeta
      after amino acid 42 can occur within the ER and later within the secretory
      pathway within the Golgi. Moreover inhibition of reinternalization by cytoplasmic
      deletions of betaAPP as well as inhibition of intracellular acidification by
      NH4Cl does not block intracellular Abeta1-42 or Abetax-42 production.

PMID- 9195902
TI  - Expression of a constitutively active phosphatidylinositol 3-kinase induces
      process formation in rat PC12 cells. Use of Cre/loxP recombination system.
AB  - It has been shown that inhibition of phosphatidylinositol (PI) 3-kinase blocks
      neurite outgrowth of PC12 cells stimulated with nerve growth factor. To further
      assess the role of PI 3-kinase, the active form of PI 3-kinase was expressed in
      PC12 cells by the adenovirus mediated introduction of a site-specific
      recombinase, Cre. After expression of the active PI 3-kinase, elevation of the
      levels of PI 3,4-diphosphate and PI 3,4,5-trisphosphate as well as formation of
      neurite-like processes was observed. The process formation was inhibited by
      wortmannin, a selective inhibitor of PI 3-kinase, which suggests that a high
      activity of PI 3-kinase was responsible for the formation of these processes. The
      processes lacked accumulation of F-actin and GAP43 at the growth cone, which
      suggests that the processes were incomplete compared with neurites. Instead, the
      bundling of microtubules was enhanced, which suggests that organization of the
      microtubules might be driving the process of elongation in the cells expressing
      the active PI 3-kinase. Induction of active PI 3-kinase resulted in activation of
      Jun N-terminal kinase but not of mitogen-activated protein kinase or protein
      kinase B/Rac protein kinase/Akt. These results suggest that PI 3-kinase is
      involved in neurite outgrowth in PC12 cells and that activation of Jun N-terminal
      kinase cascade may be involved in the cell response.

PMID- 9195903
TI  - Prenylation of RhoB is required for its cell transforming function but not its
      ability to activate serum response element-dependent transcription.
AB  - Rho regulates cytoskeletal actin structure and integrin-mediated cell adhesion.
      Rho also has a role in cell growth regulation and is required for cell
      transformation by oncogenic Ras. Recently, it has been demonstrated that Rho can
      activate transcription from the c-fos serum response element (SRE). This raised
      the possibility that functions required for Rho-mediated cell transformation
      might overlap with those involved in transcriptional regulation. Here we show
      that RhoB can activate the SRE and can synergize in cell transformation with
      constitutively activated Raf-CAAX. Significantly, unprenylated forms of RhoB that
      are biologically inert and unable to transform cells can still activate SRE
      dependent transcription. This finding suggests that transcriptional activation by
      Rho may be separable from its cell transforming functions.

PMID- 9195904
TI  - Tyrosine 140 of the gamma-aminobutyric acid transporter GAT-1 plays a critical
      role in neurotransmitter recognition.
AB  - The gamma-aminobutyric acid (GABA) transporter GAT-1 is located in nerve
      terminals and catalyzes the electrogenic reuptake of the neurotransmitter with
      two sodium ions and one chloride. We now identify a single tyrosine residue that
      is critical for GABA recognition and transport. It is completely conserved
      throughout the superfamily, and even substitution to the other aromatic amino
      acids, phenylalanine (Y140F) and tryptophan (Y140W), results in completely
      inactive transporters. Electrophysiological characterization reveals that both
      mutant transporters exhibit the sodium-dependent transient currents associated
      with sodium binding as well as the chloride-dependent lithium leak currents
      characteristic of GAT-1. On the other hand, in both mutants GABA is neither able
      to induce a steady-state transport current nor to block their transient currents.
      The nontransportable analog SKF 100330A potently inhibits the sodium-dependent
      transient in the wild type GAT-1 but not in the Y140W transporter. It partly
      blocks the transient of Y140F. Thus, although sodium and chloride binding are
      unimpaired in the tyrosine mutants, they have a specific defect in the binding of
      GABA. The total conservation of the residue throughout the family suggests that
      tyrosine 140 may be involved in the liganding of the amino group, the moiety
      common to all of the neurotransmitters.

PMID- 9195905
TI  - Ssd1p of Saccharomyces cerevisiae associates with RNA.
AB  - The SSD1 gene has been isolated as a single copy suppressor of many mutants, such
      as sit4, slk1/bck1, pde2, and rpc31, in the yeast Saccharomyces cerevisiae. Ssd1p
      has domains showing weak but significant homology with RNase II-related proteins,
      Cyt4p, Dss1p, VacB, and RNase II, which are involved in the modification of RNA.
      We found that Ssd1p had the ability to bind RNA, preferably poly(rA), as well as
      single-stranded DNA. Interestingly, the most conserved domain among the RNase II
      related proteins was not necessary for interaction with RNA. Indirect
      immunofluorescence staining with anti-Ssd1p antibody revealed that Ssd1p was
      detected mainly in the cytoplasm. Furthermore, sucrose gradient sedimentation
      analysis demonstrated that Ssd1p was not cofractionated with polyribosomes,
      suggesting that Ssd1p is not particularly bound to a translationally active
      subpopulation of mRNA in the cytoplasm.

PMID- 9195906
TI  - Identification of a Saccharomyces gene, LCB3, necessary for incorporation of
      exogenous long chain bases into sphingolipids.
AB  - To identify genes necessary for sphingolipid synthesis in Saccharomyces
      cerevisiae we developed a procedure to enrich for mutants unable to incorporate
      exogenous long chain base into sphingolipids. We show here that a mutant strain,
      AG84-3, isolated by using the enrichment procedure, makes sphingolipids from
      endogenously synthesized but not from exogenously supplied long chain base. A
      gene termed LCB3 (YJL134W, GenBank designation X87371x21), which complements the
      long chain base utilization defect of strain AG84-3, was isolated from a genomic
      DNA library. The gene is predicted to encode a protein with multiple membrane
      spanning domains and a COOH-terminal glycosylphosphatidylinositiol
      cleavage/attachment site. Deletion of the lcb3 gene in a wild type genetic
      background reduces the rate of exogenous long chain base incorporation into
      sphingolipids and makes the host strain more resistant to growth inhibition by
      long chain bases. Only one protein in current data bases, the S. cerevisiae open
      reading frame YKR053C, whose function is unknown, shows homology to the Lcb3
      protein. The two proteins are not, however, functional homologs because deletion
      of the YKR053C open reading frame does not impair long chain base utilization or
      enhance resistance of cells to growth inhibition by long chain bases. Based upon
      these data we hypothesize that the Lcb3 protein is a plasma membrane transporter
      capable of transporting sphingoid long chain bases into cells. It is the first
      candidate for such a transporter and the first member of what appears to be a new
      class of membrane-bound proteins.

PMID- 9195907
TI  - Cell cycle-dependent metabolism of pyrimidine deoxynucleoside triphosphates in
      CEM cells.
AB  - We incorporated 3H-labeled thymidine, deoxycytidine, or cytidine into dNTPs and
      DNA of exponentially growing CEM cells. G1 and S phase cells were separated by
      centrifugal elutriation, and the size and specific activity of dNTP pools were
      determined to study the cell cycle-dependent regulation of specific dNTP
      synthesizing enzymes in their metabolic context. With [3H]thymidine, we confirm
      the earlier demonstrated S phase specificity of thymidine kinase. Incorporation
      of radioactivity from [5-3H]deoxycytidine into dCTP occurred almost exclusively
      in G1 cells. During S phase, de novo synthesis by ribonucleotide reductase was
      switched on, resulting in a 70-fold dilution of [3H]dCTP, confirming that
      ribonucleotide reductase is an S phase-specific enzyme, whereas deoxycytidine
      kinase is not. [5-3H]Cytidine appeared in dCTP almost to the same extent in G1 as
      in S phase, despite the S phase specificity of ribonucleotide reductase. During S
      phase, DNA replication greatly increased the turnover of dCTP, requiring a
      corresponding increase in ribonucleotide reductase activity. During G1, the
      enzyme maintained activity to provide dNTPs for DNA repair and mitochondrial DNA
      synthesis. The poor incorporation of isotope from deoxycytidine into DNA earlier
      led to the suggestion that the nucleoside is used only for DNA repair (Xu, Y-Z.,
      Peng, H., and Plunkett, W. (1995) J. Biol. Chem. 270, 631-637). The poor
      phosphorylation of deoxycytidine in S phase provides a better explanation.

PMID- 9195908
TI  - Modulation of glutathione S-transferase subunits A2, M1, and P1 expression by
      interleukin-1beta in rat hepatocytes in primary culture.
AB  - The influence of various cytokines on the expression of glutathione S
      transferases (GSTs) was investigated in rat hepatocytes in primary culture. Only
      treatment of hepatocytes with interleukin-1beta (IL-1) was effective, resulting
      in a marked decrease in GSTs. Steady-state mRNA levels of rGSTA2 and M1 were
      strongly down-regulated by IL-1 in a dose-dependent manner after a 24-h exposure
      while rGSTP1 mRNA level was increased by a 48-h treatment. Similar effects of IL
      1 were observed at the protein level. The response to IL-1 appeared to be
      specific for each subunit within GST gene families. In addition, IL-1 strongly
      suppressed the induction of rGSTA2 by 3-methylcholanthrene, oltipraz (a synthetic
      derivative of 1, 2-dithiole-3-thione), and phenobarbital and that of rGSTM1 by
      oltipraz and phenobarbital, whereas it was ineffective on rGSTP1 induction by
      these compounds. Using in vitro nuclear run-on transcription assay and Northern
      blot analysis of alpha-amanitin-treated cells, IL-1-mediated rGSTM1 mRNA decrease
      was found to result from mRNA destabilization. These results provide the first
      demonstration that IL-1 regulates some major GST subunits in hepatocytes by a
      post-transcriptional mechanism.

PMID- 9195909
TI  - Tight junction proteins form large complexes and associate with the cytoskeleton
      in an ATP depletion model for reversible junction assembly.
AB  - A key feature of the ischemic epithelial cell phenotype is the disruption of
      tight junctions (TJ). In a Manin-Darby canine kidney cell model for ischemia
      reperfusion/hypoxia-reoxygenation injury which employs inhibitors of glycolysis
      (2-deoxy-D-glucose) and oxidative phosphorylation (antimycin A), transepithelial
      electrical resistance, a measure of TJ integrity, dropped rapidly, correlating
      well with declining ATP levels. Although immunocytochemical studies revealed only
      subtle changes in the distribution of the TJ proteins, zonula occludens (ZO)-1,
      ZO-2, and cingulin, examination of the Triton X-100 solubilities of these
      proteins, an indicator of cytoskeletal association, revealed a striking shift of
      all three TJ proteins into the insoluble pool, consistent with increased
      cytoskeletal interaction during ATP depletion. In addition, rate-zonal
      centrifugation analysis of a detergent-soluble fraction showed an increase in the
      amount of ZO-1 and ZO-2 in high density fractions following ATP depletion,
      providing further evidence for association of TJ proteins into a large complex
      possibly involving the cytoskeleton. Analysis of immunoprecipitation data from
      [35S]methionine-labeled cells revealed that ATP depletion led to the association
      of a 240-kDa protein with the ZO-1-containing complex. Western blots of this
      protein immunoprecipitated with anti-ZO-1 antibodies confirmed its identity as
      fodrin, a protein believed to link membrane and other proteins to the actin-based
      cytoskeleton. Together, our data suggest that in the absence of major
      immunocytochemical changes, ATP depletion leads TJ proteins to form large
      insoluble complexes and associate with the cytoskeleton. We propose a model in
      which a key, potentially regulated, step in the generation of the ischemic
      epithelial cell phenotype is the interaction between TJ proteins and fodrin
      and/or other cytoskeletal proteins.

PMID- 9195911
TI  - Reconstitution of phagosome-lysosome fusion in streptolysin O-permeabilized
      cells.
AB  - We have reconstituted fusion between phagosomes and lysosomes in streptolysin O
      permeabilized J774-E macrophages. Fusion was assessed by measuring the delivery
      of avidin-conjugated horseradish peroxidase pre-internalized into lysosomes to
      phagosomes containing biotinylated beta-glucuronidase-conjugated paramagnetic
      beads (1-2 microm). Fusion was dependent on energy and exogenously supplied
      cytosol. Phagosome-lysosome fusion was greatly inhibited when microtubules were
      depolymerized by nocodazole treatment, suggesting that fusion occurs via
      microtubule-dependent transport. Furthermore, fusion was inhibited by GTPgammaS
      and Rab GDP dissociation inhibitor. These results suggest that rab proteins are
      involved in the regulation of fusion. Lastly, anti-NEM-sensitive factor (NSF)
      antibodies inhibited fusion, and addition of recombinant NSF wild type partially
      restored the fusogenic activity, indicating that NSF is required for fusion
      between phagosomes and lysosomes.

PMID- 9195910
TI  - Water and glycerol permeabilities of aquaporins 1-5 and MIP determined
      quantitatively by expression of epitope-tagged constructs in Xenopus oocytes.
AB  - The goal of this study was to compare single channel water and glycerol
      permeabilities of mammalian aquaporins (AQP) 1-5 and the major intrinsic protein
      of lens fiber (MIP). Each of the six cloned cDNAs from rat was left untagged or
      was epitope-tagged with c-Myc or FLAG at either the N or C terminus so that
      results would not depend on epitope identity or location. The constructs were
      expressed in Xenopus oocytes for measurement of osmotic water permeability (Pf),
      [3H]glycerol uptake, and protein expression. Each of the 30 epitope-tagged
      constructs was expressed strongly at the oocyte plasma membrane. The 10-min
      uptake of [3H]glycerol was increased significantly (range of 4.5-8-fold over
      control) in oocytes expressing untagged AQP3 (GLIP) and each of the four tagged
      AQP3 constructs; [3H]glycerol uptake was not increased in oocytes expressing
      AQP1, AQP2, AQP4, AQP5, or MIP. In oocytes microinjected with 5 ng of cRNA,
      average Pf values (in cm/s x 10(-3)) were 0.67 +/- 0.06 (control), 19 +/- 2
      (AQP1), 10 +/- 1 (AQP2), 8 +/- 2 (AQP3), 29 +/- 1 (AQP4), 10 +/- 1 (AQP5), and
      1.3 +/- 0.2 (MIP), and they were relatively insensitive to the presence,
      identity, or location of the epitope tag. Pf values were not affected by protein
      kinase A or C activation. After normalization for plasma membrane expression by
      immunoprecipitation of microdissected plasma membranes, single channel water
      permeabilities (pf, referenced to the AQP1 pf of 6 x 10(-14) cm3/s) were (in
      cm3/s x 10(-14)) 3.3 +/- 0.2 (AQP2), 2.1 +/- 0.3 (AQP3), 24 +/- 0.6 (AQP4), 5.0
      +/- 0.4 (AQP5), and 0.25 +/- 0.05 (MIP); pf values were insensitive to epitope
      identity and location. These results indicate very different intrinsic water
      permeabilities for the mammalian aquaporin homologs, with the pf value for AQP4
      remarkably higher than those for the others. The pf values establish limits on
      aquaporin tissue densities required for physiological function and suggest
      significant structural and functional differences among the aquaporins.

PMID- 9195912
TI  - Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A)
      mRNA in human skeletal muscle and heart.
AB  - To further our understanding of the structure and function of phosphodiesterases
      of the newly identified family of high affinity cAMP-specific phosphodiesterases
      (PDE7), we identified and characterized the isozyme expressed in human skeletal
      muscle and the protein product of the previously isolated isozyme HCP1
      (designated HSPDE7A1). We report the isolation of a cDNA encoding the full-length
      skeletal muscle isoform of human PDE7A (HSPDE7A2). The DNA sequence of this
      skeletal muscle cDNA indicates that PDE7A2 is a novel 5' splice variant of PDE7A
      encoding an isoform with a novel, hydrophobic N terminus. The 456-amino acid
      PDE7A2 protein is detected on Western blots as a band with an apparent mobility
      of 50 kDa. PDE7A2 is a high affinity cAMP-specific PDE (Km = 0.1 microM), which
      is localized to particulate cellular fractions. The PDE7A1 (HCP1) isozyme is
      detected on Western blots as a band with an apparent mobility of 57 kDa,
      demonstrating that the previously isolated HCP1 cDNA encodes the full-length
      PDE7A1 protein. The even distribution of PDE7A mRNA among fetal tissues and the
      relative abundance of its two mRNAs strongly suggest that the expression of PDE7A
      is regulated throughout development.

PMID- 9195913
TI  - Involvement of the M7/M8 extracellular loop of the sodium pump alpha subunit in
      ion transport. Structural and functional homology to P-loops of ion channels.
AB  - Mutations were introduced in the motif 884DDRW887 from an extracellular peptide
      of the sodium pump alpha subunit localized between M7 and M8 membrane spans to
      investigate a possible role of this structure in ion recognition. A homologous
      sequence 399QDCW402 that occurs in the P-loops of Na+ channels was shown earlier
      to be important for ion gating. Mutant sodium pumps were expressed in yeast and
      subsequently investigated for their behavior toward ouabain, Na+, K+, and ATP.
      Native enzyme and D884A, D884R, D885A, D885E, or D885R mutants all bind ouabain
      in the presence of phosphate and Mg2+. The KD values determined from Scatchard
      analysis are in the range 5-8 nM for the native enzyme and the D884A, D885E, or
      D885A mutants, and 15.7 +/- 2.04 and 30.1 +/- 4.32 nM for mutants D884R and
      D885R, respectively. This ouabain binding is reduced in the presence of K+ in a
      similar way for both native or mutant sodium pumps with relative affinities
      (K0.5) for K+ ranging from 1.4 to 3.7 mM. Ouabain binding in the presence of 100
      microM ATP is promoted by Na+ with K0.5 = 1.64 +/- 0.01 mM for the native enzyme
      and K0.5 = 8. 6 +/- 1.35 mM for the D884R mutant. The K0.5 values of the two
      enzymes for ATP are 0.66 +/- 0.16 microM and 1.1 +/- 0.12 microM, respectively.
      Ouabain binding as a function of Na+ concentration, on the other hand, is very
      low for the D885R mutant, even at an ATP concentration of 2 mM. Phosphate or
      eosin, however, are recognized by this mutant enzyme, so that a major
      conformational change within the ATP-binding site appears unlikely. The inability
      of the D885R mutant to bind ouabain in the presence of Na+ and ATP could be
      explained by assuming that the M7/M8 connecting extracellular loop, which also
      contains the mutated amino acids, is invaginated within the plane of the plasma
      membrane and possibly involved in acceptance and/or release of Na+ ions coming
      from cytosolic areas of the protein. In this case, the placement of an additional
      positive charge might repel Na+ ions and interrupt their flow, thus not allowing
      the enzyme to assume the proper conformational state for ouabain binding. Such
      invaginated hydrophilic protein structures, such as the P-loops of Na+ and K+
      channels, are already known and have been shown to participate in ion conduction.

PMID- 9195914
TI  - Chemokine antagonists that discriminate between interleukin-8 receptors.
      Selective blockers of CXCR2.
AB  - Human neutrophils express two interleukin (IL)-8 receptors, CXC chemokine
      receptor (CXCR) 1 and CXCR2. IL-8 with changes to the NH2-terminal ELR motif can
      block IL-8-induced neutrophil functions (Moser, B., Dewald, B., Barella, L.,
      Schumacher, C., Baggiolini, M., and Clark-Lewis, I. (1993) J. Biol. Chem. 268,
      7125-7128). We have now examined the effect of NH2-terminally modified analogs of
      IL-8, GROalpha, and PF4 on CXCR1 and CXCR2 independently. Using stable Jurkat
      transfectants expressing either CXCR1 or CXCR2, it was shown that analogs derived
      from IL-8 bound both IL-8 receptors with similar affinity and could block IL-8
      induced Ca2+ mobilization. By contrast, analogs of GROalpha and PF4, (R)GROalpha
      and (R)PF4, bound only CXCR2 with high affinity and blocked Ca2+ mobilization
      induced only via CXCR2. The differential effect on CXCR1 and CXCR2 was also
      demonstrated in studies with isolated neutrophils. Thus (R)GROalpha and (R)PF4
      inhibited only the GROalpha but not the IL-8-stimulated elastase release, and
      these two analogs had no effect on IL-8-elicited superoxide generation, a
      response that is mediated by CXCR1 but not by CXCR2. These results show that
      CXCR2 selective receptor antagonists can be generated based upon the secondary
      binding determinants of GROalpha and PF4. They also highlight the primary
      importance of CXCR1 in chemokine-mediated release of granule enzymes and
      superoxide generation. The selective antagonists described may be used in future
      studies on IL-8 receptor signaling to define distinct steps leading to various
      functional responses induced in neutrophils via CXCR1 and CXCR2.

PMID- 9195915
TI  - Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells.
AB  - The Philadelphia chromosome, detected in virtually all cases of chronic
      myelogenous leukemia (CML), is formed by a reciprocal translocation between
      chromosomes 9 and 22 that fuses BCR-encoded sequences upstream of exon 2 of c
      ABL. The BCR-ABL fusion creates a gene whose protein product, p210BCR-ABL, has
      been implicated as the cause of the disease. Although ABL kinase activity has
      been shown to be required for the transforming abilities of BCR-ABL and numerous
      substrates of the BCR-ABL tyrosine kinase have been identified, the requirement
      of most of these substrates for the transforming function of BCR-ABL is unknown.
      In this study we mapped a direct binding site of the c-CBL proto-oncogene to the
      SH2 domain of BCR-ABL. This interaction only occurs under conditions where c-CBL
      is tyrosine-phosphorylated. Despite the direct interaction of c-CBL with the SH2
      domain of BCR-ABL, deletion of the SH2 domain of BCR-ABL did not result in an
      alteration in the complex formation of BCR-ABL and c-CBL, suggesting that another
      site of direct interaction between c-CBL and BCR-ABL exists or that another
      protein mediates an indirect interaction of c-CBL and BCR-ABL. Since CRKL, an
      SH2, SH3 domain-containing adapter protein is known to bind directly to BCR-ABL
      and also binds to tyrosine-phosphorylated c-CBL, the ability of CRKL to mediate a
      complex between c-CBL and BCR-ABL was examined.

PMID- 9195916
TI  - Probing the ubiquinone reduction site of mitochondrial complex I using novel
      cationic inhibitors.
AB  - A wide variety of N-methylpyridinium and quinolinium cationic inhibitors of
      mitochondrial complex I was synthesized to develop potent and specific inhibitors
      acting selectively at one of the two proposed ubiquinone binding sites of this
      enzyme (Gluck, M. R., Krueger, M. J., Ramsay, R. R., Sablin, S. O., Singer, T.
      P., and Nicklas, W. J. (1994) J. Biol. Chem. 269, 3167-3174). N-Methyl-2-n
      dodecyl-3-methylquinolinium (MQ18) inhibited electron transfer of complex I at
      under microM order regardless of whether exogenous or endogenous ubiquinone was
      used as an electron acceptor. The presence of tetraphenylboron (TPB-) potentiated
      the inhibition by MQ18 in a different way depending upon the molar ratio of TPB-
      to MQ18. In the presence of a catalytic amount of TPB-, the inhibitory potency of
      MQ18 was remarkably enhanced, and the extent of inhibition was almost complete.
      The presence of equimolar TPB- partially reactivated the enzyme activity, and the
      inhibition was saturated at an incomplete level (approximately 50%). These
      results are explained by the proposed dual binding sites model for ubiquinone
      (cited above). The inhibition behavior of MQ18 for proton pumping activity was
      similar to that for electron transfer activity. The good correlation of the
      inhibition behavior for the two activities indicates that both ubiquinone binding
      sites contribute to redox-driven proton pumping. On the other hand, N-methyl-4-[2
      methyl-3-(p-tert-butylphenyl)]propylpyridinium (MP6) without TPB- brought about
      approximately 50% inhibition at 5 microM, but the inhibition reached a plateau at
      this level over a wide range of concentrations. Almost complete inhibition was
      readily obtained at low concentrations of MP6 in the presence of TPB-. Thus MP6
      appears to be a selective inhibitor of one of the two ubiquinone binding sites.
      With a combined use of MP6 and 2,3-diethoxy-5-methyl-6-geranyl-1,4-benzoquinone,
      we also provided kinetic evidence for the existence of two ubiquinone binding
      sites.

PMID- 9195917
TI  - Domain analysis of the molecular recognition features of aromatic polyketide
      synthase subunits.
AB  - Bacterial aromatic polyketide synthases (PKSs) are a family of homologous
      multienzyme assemblies that catalyze the biosynthesis of numerous polyfunctional
      aromatic natural products. In the absence of direct insights into their
      structures, the use of gene fusions can be a powerful tool for understanding the
      structural basis for their properties. A series of truncated and hybrid proteins
      were constructed and analyzed within a family of PKS subunits, designated
      aromatases/cyclases (ARO/CYCs). When expressed alone, neither the N-terminal nor
      the C-terminal domain of the actinorhodin (act) or the griseusin (gris) ARO/CYC
      exhibited substantial aromatase activity. However, in the presence of each other,
      the half proteins were active. Furthermore, analysis of a set of hybrid proteins
      derived from the act and gris ARO/CYCs allowed us to localize the chain length
      dependence of this aromatase activity to their N-terminal domains. Unexpectedly,
      however, when the C-terminal domain of the gris ARO/CYC was expressed in a
      context where aromatase activity was absent, it could modulate the chain length
      specificity of the tetracenomycin (tcm) minimal PKS, leading to the formation of
      a novel 18-carbon product in addition to the expected 20-carbon one. It was also
      found that monodomain ARO/CYCs such as tcmN cannot substitute for the the N
      terminal domain of didomain ARO/CYCs, even though they exhibit high sequence
      similarity with the N-terminal domain. Together, these results illustrate the
      utility of protein engineering approaches for dissecting the structure-function
      relationships of PKS subunits and for the generation of mutant alleles with novel
      biosynthetic properties.

PMID- 9195918
TI  - Binding of src-like kinases to the beta-subunit of the interleukin-3 receptor.
AB  - We have previously shown that stimulation of 32D cl3 cells with interleukin (IL)
      3 results in the activation of three src-like tyrosine kinases, fyn, hck, and
      lyn. The beta subunit of the IL-3 receptor co-immunoprecipitated with hck in
      lysates of both unstimulated and IL-3-stimulated cells; however, the beta subunit
      did not precipitate with either fyn or lyn. The association of these three
      kinases with the beta subunit of the IL-3 receptor was further investigated using
      bacterial fusion proteins encoding the unique, SH3, and SH2 domains of these
      three kinases. Fusion proteins of both hck and fyn bound to a 150-kDa tyrosine
      phosphorylated protein present in lysates of IL-3-stimulated cells. This protein
      was identified as the beta subunit of the IL-3 receptor by immunoblotting with an
      anti-beta antibody. Glutathione S-transferase (GST) fusion proteins containing
      the SH2 domain of hck bound to the beta subunit although the amount of beta
      subunit that bound to the SH2 domain alone was only 30% of that which bound to
      the fusion protein containing the unique, SH3, and SH2 domains. This indicates
      that the SH2 domain is one of the motifs involved in binding hck to the beta
      subunit. A GST fusion protein encoding a 236-amino acid region of the cytoplasmic
      tail of the beta subunit, which contained four tyrosine residues, bound to hck
      and fyn. Binding to both proteins was dramatically increased when the GST-beta
      fusion protein was tyrosine-phosphorylated. Far Western blot analysis was used to
      demonstrate the binding of the unique, SH3, and SH2 domains of hck to this 236
      amino acid region of the beta subunit; tyrosine phosphorylation of this protein
      increased the binding of both the unique region and the SH2 domain probes. These
      data indicate that binding of hck to the beta subunit is mediated by both
      phosphotyrosine-dependent and -independent mechanisms.

PMID- 9195919
TI  - A metal-induced conformational change and activation of HIV-1 integrase.
AB  - Retroviral integrases are composed of three independently folding domains whose
      organization relevant to one another is largely unknown. As an approach to
      understanding its structure, we have investigated the effect of the required
      metal cofactor(s), Mn2+ or Mg2+, on the conformation of human immunodeficiency
      virus type 1 (HIV-1) integrase (IN) using monoclonal antibodies (mAbs) that are
      specific for each of these three domains. Upon the addition of increasing
      concentrations of the divalent cations to immobilized HIV-1 IN in ELISA assays,
      binding of mAbs specific for either the C-terminal domain or for an epitope in
      the catalytic core domain was lost, whereas binding of an N terminus-specific mAb
      was unaffected. Size exclusion chromatography of a nonaggregating derivative of
      HIV-1 IN showed that the oligomeric state of the protein did not change under
      conditions in which recognition of the core and C terminus-specific mAbs was
      lost. Preincubation with Mn2+ increased the resistance of HIV-1 IN to proteolytic
      digestion and produced a digestion pattern that was significantly different from
      that observed with the apoprotein. A derivative that lacked the N-terminal
      domain, IN(50-288), exhibited the same metal-dependent changes observed with the
      full-length protein, whereas the isolated catalytic core domain IN(50-212) did
      not. From this we conclude that the metal-induced conformational change comprises
      a reorganization of the core and C-terminal domains. Preincubation with Mn2+
      increased the specific activity of HIV-1 IN 5-fold. Enzymatic activity was
      inhibited by the conformation-sensitive C terminus-specific mAb, but this
      inhibition was reduced greatly if the enzyme was first preincubated with metal
      ions. Thus, it appears that apo-HIV-1 IN exists predominantly in an inactive
      conformation that is converted into a catalytically competent form upon the
      addition of metal ions.

PMID- 9195920
TI  - Effect of Mg(II) binding on the structure and activity of Escherichia coli DNA
      topoisomerase I.
AB  - Escherichia coli DNA topoisomerase I requires Mg(II) as a cofactor for the
      relaxation of negatively supercoiled DNA. Mg(II) binding to the enzyme was shown
      by fluorescence spectroscopy to affect the tertiary structure of the enzyme.
      Addition of 2 mM MgCl2 resulted in a 30% decrease in the maximum emission of
      tryptophan fluorescence of the enzyme. These Mg(II)-induced changes in
      fluorescence properties were reversible by the addition of EDTA and not obtained
      with other divalent cations. After incubation with Mg(II) and dialysis,
      inductively coupled plasma (ICP) analysis showed that each enzyme molecule could
      form a complex with 1-2 Mg(II) bound to each enzyme molecule. Such Mg(II).enzyme
      complexes were found to be active in the relaxation of negatively supercoiled DNA
      in the absence of additional Mg(II). Results from ICP analysis after equilibrium
      dialysis and relaxation assays with limiting Mg(II) concentrations indicated that
      both Mg(II) binding sites had to be occupied for the enzyme to catalyze
      relaxation of negatively supercoiled DNA.

PMID- 9195921
TI  - Sphingosine 1-phosphate stimulates tyrosine phosphorylation of Crk.
AB  - The proto-oncogene molecule c-Crk plays a role in growth factor-induced
      activation of Ras. Sphingosine 1-phosphate (SPP), a metabolite of cellular
      sphingolipids, has previously been shown to play a role in growth factor receptor
      signaling (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560). SPP was
      found to strongly induce tyrosine phosphorylation of Crk, but not Shc, in NIH-3T3
      parental, insulin-like growth factor-I receptor-overexpressing and Crk
      overexpressing (3T3-Crk) fibroblasts. Sphingosine, a metabolic precursor of SPP,
      also produced a slight increase in tyrosine phosphorylation of Crk. In contrast,
      other sphingolipid metabolites including ceramide did not alter Crk tyrosine
      phosphorylation. Furthermore, Crk enhanced SPP-induced mitogenesis, as measured
      by SPP-stimulated [3H]thymidine incorporation in a manner proportional to the
      level of Crk expression in 3T3-Crk cells. This stimulation appears to be Ras
      dependent, whereas SPP stimulation of MAP kinase activity is Ras-independent.
      These data indicate that SPP activates a tyrosine kinase that phosphorylates Crk
      and that Crk is a positive effector of SPP-induced mitogenesis.

PMID- 9195922
TI  - Leptin receptor action in hepatic cells.
AB  - Leptin, an adipocyte-secreted hormone, is one of the central regulators of body
      weight homeostasis. In humans and rodents, two major forms of leptin receptors
      (OB-R) are expressed. The short form (OB-RS), considered to lack signaling
      capability, is detected in many organs. In contrast, OB-R long form (OB-RL)
      predominates in the hypothalamus, but is also present at low levels in peripheral
      tissues. Transient transfection experiments have demonstrated that OB-RL
      transduces an intracellular signaling similar to interleukin (IL)-6 type-cytokine
      receptors. To define the specificity by which OB-R induces genes and cooperates
      with signal transduction pathways utilized by other hormones and cytokines, rat
      and human hepatoma cell lines were generated which stably express human OB-RL.
      Hepatoma cell lines selected for appreciable levels of OB-RL mRNA display
      enhanced leptin binding and responded to leptin with an IL-6 receptor-like
      signaling that includes the activation of STAT proteins, induction of acute-phase
      plasma proteins, and synergism with IL-1 and tumor necrosis factor-alpha. A
      leptin-mediated recruitment of phosphatidylinositol 3-kinase to insulin receptor
      substrate-2 was also detected. However, no significant tyrosine phosphorylation
      of insulin receptor substrate-2 and modulation of the immediate cell response to
      insulin were observed. The data suggest that OB-RL action in hepatic cells is
      equivalent to that of IL-6 receptor. However, leptin does not play a specific
      role in muting insulin action on hepatoma cells and therefore may not contribute
      to the diabetic symptoms associated with obesity.

PMID- 9195923
TI  - Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90
      complexes with properties of an FK506-binding immunophilin.
AB  - Steroid receptors are recovered from hormone-free cells in multiprotein complexes
      containing hsp90, p23, an immunophilin, and often some hsp70. The immunophilin,
      which can be of the FK506- or cyclosporin A-binding class, binds to hsp90 via its
      tetratricopeptide repeat (TPR) domain, and different receptor heterocomplexes
      exist depending upon which immunophilin occupies the TPR-binding region of hsp90.
      We have recently reported that a protein serine/threonine phosphatase that is
      designated PP5 and contains four TPRs binds to hsp90 and is co-purified with the
      glucocorticoid receptor (GR) (Chen, M.-S., Silverstein, A. M., Pratt, W. B., and
      Chinkers, M. (1996) J. Biol. Chem. 271, 32315-32320). In this work, we show that
      PP5 is recovered with both GR that is nuclear and GR that is cytoplasmic in
      hormone-free cells. Approximately one-half of the GR.hsp90 heterocomplexes in L
      cell cytosol contains an immunophilin with high affinity FK506 binding activity,
      such as FKBP51 or FKBP52, and approximately 35% contains PP5. Only a small (but
      undetermined) fraction of the native GR.hsp90 heterocomplexes contain the
      cyclosporin A-binding immunophilin CyP-40. PP5, FKBP52, and CyP-40 exist in
      separate heterocomplexes with hsp90, and competition binding experiments with the
      PP5 TPR domain suggest that the three proteins occupy a common binding site on
      hsp90. A 55-residue connecting region between the N-terminal TPR domain of human
      PP5 and its C-terminal phosphatase domain has 50% amino acid homology and 22%
      identity with the central portion of the peptidylprolyl isomerase domain of human
      FKBP52. Of the 9 residues in this portion of FKBP52 involved in high affinity
      interactions with FK506, 3 residues are retained and 4 have homologous
      substitutions in PP5. Although immunoadsorbed PP5 did not bind [3H]FK506, we
      found that both rabbit PP5 in reticulocyte lysate and purified rat PP5 were
      specifically retained by an FK506 affinity matrix. Thus, we propose that PP5
      possesses properties of an immunophilin with low affinity FK506 binding activity
      and that it determines a major portion of the native GR heterocomplexes in L cell
      cytosol.

PMID- 9195924
TI  - Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized
      polar phospholipids generated during lipoprotein oxidation.
AB  - Although the major function of lecithin-cholesterol acyltransferase (LCAT) is
      cholesterol esterification, our previous studies showed that it can also
      hydrolyze platelet-activating factor (PAF). Because of the structural
      similarities between PAF and the truncated phosphatidylcholines (polar PCs)
      generated during lipoprotein oxidation, we investigated the possibility that LCAT
      may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF
      acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma,
      was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride
      (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this
      concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP)
      completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation
      during the oxidation of plasma increased by 44% in the presence of 0.2 mM
      Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was
      concomitantly inhibited by both of the inhibitors. The combination of the two
      inhibitors resulted in the maximum accumulation of polar PCs, suggesting that
      both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken
      plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC
      from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either
      isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were
      hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These
      results demonstrate a novel function for LCAT in the detoxification of polar PCs
      generated during lipoprotein oxidation, especially when the PAF-AH is absent or
      inactivated.

PMID- 9195925
TI  - A single amino acid substitution in the pleckstrin homology domain of
      phospholipase C delta1 enhances the rate of substrate hydrolysis.
AB  - The pleckstrin homology (PH) domain has been postulated to serve as an anchor for
      enzymes that operate at a lipid/water interface. To understand further the
      relationship between the PH domain and enzyme activity, a phospholipase C (PLC)
      delta1/PH domain enhancement-of-activity mutant was generated. A lysine residue
      was substituted for glutamic acid in the PH domain of PLC delta1 at position 54
      (E54K). Purified native and mutant enzymes were characterized using a
      phosphatidylinositol 4,5-bisphosphate (PI(4, 5)P2)/dodecyl maltoside mixed
      micelle assay and kinetics measured according to the dual phospholipid model of
      Dennis and co-workers (Hendrickson, H. S., and Dennis, E. A. (1984) J. Biol.
      Chem. 259, 5734-5739; Carmen, G. M., Deems, R. A., and Dennis, E. A. (1995) J.
      Biol. Chem. 270, 18711-18714). Our results show that both PLC delta1 and E54K
      bind phosphatidylinositol bisphosphate cooperatively (Hill coefficients, n = 2.2
      +/- 0.2 and 2.0 +/- 0.1, respectively). However, E54K shows a dramatically
      increased rate of (PI(4, 5)P2)-stimulated PI(4,5)P2 hydrolysis (interfacial Vmax
      for PLC delta1 = 4.9 +/- 0.3 micromol/min/mg and for E54K = 31 +/- 3
      micromol/min/mg) as well as PI hydrolysis (Vmax for PLC delta1 = 27 +/- 3.4
      nmol/min/mg and for E54K = 95 +/- 12 nmol/min/mg). In the absence of PI(4,5)P2
      both native and mutant enzyme hydrolyze PI at similar rates. E54K also has a
      higher affinity for micellar substrate (equilibrium dissociation constant, Ks =
      85 +/- 36 microM for E54K and 210 +/- 48 microM for PLC delta1). Centrifugation
      binding assays using large unilamelar phospholipid vesicles confirm that E54K
      binds PI(4,5)P2 with higher affinity than native enzyme. E54K is more active even
      though the interfacial Michaelis constant (Km) for E54K (0.034 +/- 0.01 mol
      fraction PI(4,5)P2) is higher than the Km for native enzyme (0.012 +/- 0.002 mol
      fraction PI(4,5)P2). D-Inositol trisphosphate is less potent at inhibiting E54K
      PI(4,5)P2 hydrolysis compared with native enzyme. These results demonstrate that
      a single amino acid substitution in the PH domain of PLC delta1 can dramatically
      enhance enzyme activity. Additionally, the marked increase in Vmax for E54K
      argues for a direct role of PH domains in regulating catalysis by allosteric
      modulation of enzyme structure.

PMID- 9195926
TI  - Translation initiation factors eIF-iso4G and eIF-4B interact with the poly(A)
      binding protein and increase its RNA binding activity.
AB  - The 5'-cap and the poly(A) tail act synergistically to increase the translational
      efficiency of eukaryotic mRNAs, which suggests that these two mRNA elements
      communicate during translation. We report here that the cap-associated eukaryotic
      initiation factors (eIFs), i. e. the two isoforms of the cap-binding complex (eIF
      4F and eIF-iso4F) and eIF-4B, bind to the poly(A)-binding protein (PABP) both in
      the presence and absence of poly(A) RNA. The interactions between PABP and eIF
      4F, eIF-iso4F, and eIF-4B were measured in the absence of poly(A) RNA using far
      Western analysis and confirmed by direct fluorescence titration studies. The
      functional consequence of the interaction between these initiation factors and
      PABP was examined using RNA binding assays and RNA mobility shift analysis. eIF
      4F, eIF-iso4F, and eIF-4B promoted PABP activity through a shift in its
      equilibrium affinity for poly(A). eIF-iso4G, the large subunit of eIF-iso4F, was
      the subunit responsible for the interaction between eIF-iso4F and PABP and was
      the subunit that promoted PABP RNA binding activity. Truncation analysis of eIF
      iso4G indicated that a domain close to its N-terminal end appeared to be involved
      in binding PABP. These results suggest that the interaction between PABP and eIF
      4B and eIF-iso4G may be involved in mediating the functional co-dependence
      observed between the cap and the poly(A) tail during translation.

PMID- 9195927
TI  - Functional analysis of nodulin 26, an aquaporin in soybean root nodule
      symbiosomes.
AB  - Upon infection of soybean roots, nitrogen-fixing bacteria become enclosed in a
      specific organelle known as the symbiosome. The symbiosome membrane (SM) is a
      selectively permeable barrier that controls metabolite flux between the plant
      cytosol and the symbiotic bacterium inside. Nodulin 26 (NOD 26), a member of the
      aquaporin (AQP) water channel family, is a major protein component of the SM.
      Expression of NOD 26 in Xenopus oocytes gave a mercury-sensitive increase in
      osmotic water permeability (Pf). To define the biophysical properties of NOD 26
      water channels in their native membranes, symbiosomes were isolated from soybean
      root nodules and the SM separated as vesicles from the bacteria. Permeabilities
      were measured using stopped-flow fluorimetry in SM vesicles with entrapped
      carboxyfluorescein. Osmotic water permeability (Pf) of SM was high, with a value
      of 0.05 +/- 0.003 cm/s observed at 20 degrees C (mean +/- S.E.; n = 15). Water
      flow exhibited a low activation energy, was inhibited by HgCl2 (0.1 mM), and
      exhibited a unit conductance of 3.2 +/- 1.3 x 10(-15) cm3/s, a value 30-fold
      lower than that of AQP 1, the red blood cell water channel. Diffusive water
      permeability (Pd) was 0.0024 +/- 0.0002 cm/s, and the resulting Pf to Pd ratio
      was 18.3, indicating that water crosses the SM in single file fashion via the NOD
      26 water channel. In addition to high water permeability, SM vesicles also show
      high mercury-sensitive permeability to glycerol and formamide, but not urea,
      suggesting that NOD 26 also fluxes these solutes. Overall, we conclude that NOD
      26 acts as a water channel with a single channel conductance that is 30-fold
      lower than AQP 1. Because the solutes that permeate NOD 26 are far larger than
      water, and water appears to cross the channel via a single file pathway, solute
      flux across NOD 26 appears to occur by a pathway that is distinct from that for
      water.

PMID- 9195928
TI  - Activation of pp60c-src depending on cell density in PC12h cells.
AB  - The Src family tyrosine kinases and their substrates are involved in cell-cell
      and cell-matrix interactions. We found that in PC12h cells, an increase of cell
      density enhanced the tyrosine phosphorylation levels of several intracellular
      proteins including p130(cas). Because it is a possible substrate for Src family
      kinases, we measured pp60(c-src) activity and found that it was higher in high
      density cultures than in low density cultures. This phenomenon was also observed
      in PC12 (the parental cell line of the PC12h subclone), Balb/c 3T3, Swiss 3T3,
      and Hela cells. One of the possible mechanisms regulating the kinase activity of
      pp60(c-src) is the phosphorylation and dephosphorylation of its negative
      regulatory site located at its C terminus. However, the tyrosine phosphorylation
      level of the regulatory site did not change depending on cell density.
      Subcellular fractionation showed that in high density culture, pp60(c-src) was
      translocated from detergent-soluble to detergent-insoluble fractions. These
      results suggest that cell-cell interaction might induce the activation of pp60(c
      src) without changing its tyrosine phosphorylation levels.

PMID- 9195929
TI  - Intrinsic specificity of the reactive site loop of alpha1-antitrypsin, alpha1
      antichymotrypsin, antithrombin III, and protease nexin I.
AB  - Members of the serpin (serine protease inhibitor) family share a similar backbone
      structure but expose a variable reactive-site loop, which binds to the catalytic
      groove of the target protease. Specificity originates in part from the sequence
      of this loop and also from secondary binding sites that contribute to the
      inhibitor function. To clarify the intrinsic contribution of the reactive-site
      loop, alpha1-antichymotrypsin has been utilized as a scaffold to construct
      chimeras carrying the loop of antithrombin III, protease nexin 1, or alpha1
      antitrypsin. Reactive-site loops not only vary in sequence but also in length;
      therefore, the length of the reactive-site loop was also varied in the chimeras.
      The efficacy of the specificity transfer was evaluated by measuring the
      stoichiometry of the reaction, the ability to form an SDS-stable complex, and the
      association rate constant with a number of potential targets (chymotrypsin,
      neutrophil elastase, trypsin, thrombin, factor Xa, activated protein C, and
      urokinase). Overall, substitution of a reactive-site loop was not sufficient to
      transfer the specificity of a given serpin to alpha1-antichymotrypsin.
      Specificity of the chimera partly matched that of the loop donor and partly that
      of the acceptor, whereas the behavior as an inhibitor or a substrate depended
      upon the targeted protease. Results suggest that, aside from the contributions of
      the loop sequence and the framework-specific secondary binding sites, an
      intramolecular control may be essential for productive interaction.

PMID- 9195930
TI  - Close association of the first and fourth extracellular domains of the Duffy
      antigen/receptor for chemokines by a disulfide bond is required for ligand
      binding.
AB  - It has been demonstrated that the promiscuous chemokine binding profile of the
      Duffy antigen/receptor for chemokines (DARC) is given by its extracellular NH2
      terminal region. However, the relationship among the Fy6, Fya/b, and Fy3
      epitopes, localized in the first and fourth extracellular domains of DARC,
      respectively, and the chemokine binding sites remained a matter of controversy.
      Here, we performed cross-displacement and cross-inhibition experiments indicating
      that all anti-Fy6, anti-Fya, and anti-Fy3 monoclonal antibodies and interleukin 8
      are antagonists for binding to red cells. Biopanning of phage peptide libraries
      with an anti-Fy6 monoclonal antibody led to the identification of the motif Phe22
      Glu23, the mutation of which altered the binding of both anti-Fy6 and chemokines
      (interleukin 8, MGSA, RANTES (regulated on activation normal T cell expressed))
      to DARC transfectants. These results characterized the core of the Fy6 epitope
      and provided definitive proof of the tight relationship between Fy6 and the
      chemokine receptor site. Analysis of red cells treated by sulfhydryl group
      modifying reagents suggested that the chemokine receptor function of DARC
      required the integrity of disulfide bond(s) but not that of free sulfhydryl
      group(s). Accordingly, mutation of cysteines 51 and 276 abolished chemokine
      binding to DARC transfectants. Altogether, our results suggested that the
      chemokine binding pocket of DARC included sequences located in the first and
      fourth extracellular domains which are brought into close vicinity by a disulfide
      bridge.

PMID- 9195931
TI  - Inhibition of the neutral magnesium-dependent sphingomyelinase by glutathione.
AB  - Sphingomyelin hydrolysis through the activation of sphingomyelinases has become a
      potentially important signaling pathway with the product ceramide implicated in
      the regulation of cell growth, differentiation, apoptosis, and inflammatory
      responses. However, little is known about the regulation of sphingomyelinases. In
      this study, we show that the magnesium-dependent, neutral pH-optimum and membrane
      associated sphingomyelinase (N-SMase) is inhibited, in a dose-dependent manner,
      by glutathione (GSH) at physiological concentrations with a greater than 95%
      inhibition observed at 5 mM GSH. The inhibitory effect of GSH was reproduced by
      gamma-glutamyl-cysteine, but not the cysteinyl-glycine fragment of GSH. The S
      modified GSH analogs were as effective as GSH in inhibiting the N-SMase. On the
      other hand, neither dithiothreitol nor beta-mercaptoethanol had any effect on the
      N-SMase, suggesting that the sulfhydryl in GSH is not required for inhibition of
      N-SMase. GSH had no effect on the acid pH-optimum SMase, whereas dithiothreitol
      inhibited the acid SMase. These results suggest that in cells the N-SMase is
      inactive in the presence of physiological concentrations of GSH (1-20 mM).
      Finally, treatment of cultured Molt-4 cells with the GSH synthesis inhibitor, L
      buthionine-(SR)-sulfoximine, resulted in a time-dependent depletion of GSH,
      accompanied by an increased hydrolysis of sphingomyelin and production of
      ceramide. Since GSH depletion is observed in a variety of cells in the process of
      cellular injury and apoptosis, these studies suggest that depletion of GSH may be
      an important mechanism in activation of N-SMase. This mechanism may therefore
      bring together the fields of oxidative stress and signaling through products of
      sphingomyelin hydrolysis.

PMID- 9195932
TI  - Repression of gamma-aminobutyric acid type A receptor alpha1 polypeptide
      biosynthesis requires chronic agonist exposure.
AB  - Although it is well established that the number of gamma-aminobutyric acid type A
      (GABAA) receptors declines in cortical neurons exposed to GABAA receptor
      agonists, the mechanisms responsible for this use-dependent down-regulation
      remain unclear. Two hypotheses have been proposed: (i) agonist-evoked
      sequestration and degradation of surface GABAA receptors and (ii) repression of
      receptor subunit biosynthesis. We have addressed this problem using [35S]Met/Cys
      pulse-chase labeling of chick cortical neurons in culture and immunoprecipitation
      and immunoblotting with an antibody (RP4) directed against a GABAA receptor
      alpha1-(331-381) fusion protein. Exposure of the cells to GABA or isoguvacine for
      2 h to 4 days had no effect on the initial rate of 35S incorporation into the
      GABAA receptor 51-kDa alpha1 polypeptide, but this rate declined by 33% after a 7
      day treatment. This is consistent with a previous report (Baumgartner, B. J.,
      Harvey, R. J., Darlison, M. G., and Barnes, E. M. (1994) Mol. Brain Res. 26, 9
      17) that a 7-day GABA treatment of this preparation produced a 45% reduction in
      the alpha1 subunit mRNA level, while a 4-day exposure had no detectable effect.
      On the other hand, after a 4-day exposure to these agonists, a 30% reduction in
      the level of the alpha1 polypeptide was observed on immunoblots, similar to that
      found previously for down-regulation of GABAA receptor ligand-binding sites.
      Thus, the de novo synthesis of GABAA receptor alpha1 subunits is subject to a
      delayed use-dependent repression that was observed after, rather than before, the
      decline in neuronal levels of the polypeptide. Pulse-chase experiments showed a
      monophasic degradation of the GABAA receptor 35S-alpha1 subunit with a t1/2 = 7.7
      h, a process that was unaffected by the addition of GABA to neurons during the
      chase period. These nascent 35S-labeled polypeptides are presumably diluted into
      the neuronal pool of unlabeled unassembled alpha1 subunits, which was found to
      exceed by a 4:1 molar ratio the amount assembled into [3H]flunitrazepam binding
      sites. Thus, the data reveal an alternative scheme for degradation of GABAA
      receptor polypeptides: a pathway that may participate in the agonist-independent
      degradation of unassembled receptor subunits. This differs from another pathway
      for the agonist-dependent degradation of mature GABAA receptors derived from the
      neuronal surface (Calkin, P. A., and Barnes, E. M., Jr. (1994) J. Biol. Chem.
      269, 1548-1553).

PMID- 9195933
TI  - Sphingosylphosphocholine reduces the calcium ion requirement for activating
      tissue transglutaminase.
AB  - Tissue transglutaminase (tTG) catalyzes a Ca2+-dependent transglutaminase
      reaction resulting in the formation of gamma-glutamyl-epsilon-lysine bonds and is
      activated during apoptosis to catalyze the formation of apoptotic body. We
      investigate whether lipids that are membrane components and involved in cell
      signaling could modify the Ca2+-dependent activation of tTG. We found that
      sphingosylphosphocholine (lyso-SM) was the only lipid to activate
      transglutaminase at low Ca2+ concentrations. In the presence of lyso-SM (125
      microM), transglutaminase was detectable at 10 microM Ca2+, whereas in the
      absence of lyso-SM, similar activity was obtained at 160 microM Ca2+.
      Furthermore, in the presence of lipid vesicles lyso-SM retained the ability to
      enhance the Ca2+-dependent activation of tTG. Lyso-SM did not significantly
      change the Km for the glutamyl and primary amine substrates. However, the Kact
      for Ca2+ was reduced from 300 microM to 90 microM. Structure-function studies of
      lyso-SM analogs indicate that phosphocholine group on C1, the free amino group at
      C2 and a C4-C5 double bond are critical for the activation of transglutaminase
      activity. This is the first demonstration that a specific sphingolipid could
      enhance the activity of tTG and could play a role in vivo in activation of the
      tTG at physiologic Ca2+ levels.

PMID- 9195934
TI  - Individual residues contribute to multiple differences in ligand recognition
      between vesicular monoamine transporters 1 and 2.
AB  - Molecular cloning has identified two vesicular monoamine transporters (VMATs),
      one expressed in non-neural cells of the periphery (VMAT1) and the other by
      multiple monoamine cell populations in the brain (VMAT2). Functional analysis has
      previously shown that VMAT2 has a higher affinity than VMAT1 for monoamine
      neurotransmitters as well as the inhibitor tetrabenazine. The analysis of
      chimeric transporters has also identified two major regions required for the high
      affinity interactions of VMAT2 with these ligands. We have now used site-directed
      mutagenesis to identify the individual residues responsible for these
      differences. Focusing on the region that spans transmembrane domains 9 through
      12, we have replaced VMAT2 residues with the corresponding residues from VMAT1.
      Many residues in this region had no effect on the recognition of these ligands,
      but substitution of Tyr-434 with Phe and Asp-461 with Asn reduced the affinity
      for tetrabenazine, histamine, and serotonin. Although the ability to affect
      recognition of multiple ligands suggests a general structural role for these
      residues, the mutations did not affect dopamine recognition, indicating a more
      specific role, possibly in recognition of the ring nitrogen that occurs in
      tetrabenazine, histamine, and serotonin but not dopamine. The mutation K446Q
      reduced the affinity of VMAT2 for tetrabenazine and serotonin but not histamine,
      whereas F464Y reduced serotonin affinity and perhaps histamine recognition but
      not tetrabenazine sensitivity, providing more evidence for specificity.
      Interestingly, the Vmax of both VMATs for dopamine exceeded that for serotonin by
      3-5-fold, indicating a difference in the speed of packaging of these two
      neurotransmitters. We also found that VMAT1 has a higher affinity for tryptamine
      than VMAT2. This mutually exclusive interaction with serotonin and tryptamine
      also suggests a physiological rationale for the existence of two VMATs.
      Surprisingly, the residue responsible for this difference, Tyr-434, also accounts
      for the higher affinity interaction of VMAT2 with tetrabenazine, histamine, and
      serotonin. Interestingly, replacement of Tyr-434 with alanine increases the
      affinity of VMAT2 for both serotonin and dopamine and reduces the rate of
      dopamine transport.

PMID- 9195935
TI  - Saccharomyces cerevisiae VIG9 encodes GDP-mannose pyrophosphorylase, which is
      essential for protein glycosylation.
AB  - A genomic DNA fragment that complements a newly identified protein glycosylation
      defective mutation, vig9, of Saccharomyces cerevisiae was cloned. Chromosomal
      integration of this fragment by homologous recombination indicated that it
      contains the wild type VIG9 gene. The nucleotide sequence was determined. A
      predicted gene product showed significant amino acid sequence homology with
      several bacterial enzymes that catalyze the synthesis of (deoxy)ribonucleotide
      diphosphate sugars from sugar phosphates and (deoxy)ribonucleotide triphosphate.
      We examined the enzyme activity to synthesize GDP-mannose in the cell extracts of
      the wild type, vig9-1 mutant, and VIG9 transformant yeasts. Reduction of the
      activity in the mutant cell and its restoration by VIG9 suggested that the VIG9
      gene is the structural gene for GDP-mannose pyrophosphorylase of S. cerevisiae
      which catalyzes the production of GDP-mannose. We demonstrated the enzyme
      activity of Vig9 protein using a recombinant fusion protein produced in
      Escherichia coli.

PMID- 9195936
TI  - 2'-O-Dansyl analogs of ATP bind with high affinity to the low affinity ATP site
      of Na+/K+-ATPase and reveal the interaction of two ATP sites during catalysis.
AB  - Na+/K+-transport through mammalian cell membranes by Na+/K+-ATPase (EC 3.6.1.37)
      needs the interaction of ATP sites with different binding affinities during
      catalysis: one with catalytic (high affinity site) and one with regulatory
      properties (low affinity site). To find affinity labels for the latter one, the
      effects of 2'-O-dansylated ATP analogs on Na+/K+-ATPase and its partial
      activities were analyzed. DANS-ATP (2'-O-(6
      dimethylaminonaphthalenesulfonyl)adenosine 5'-triphosphate) inhibited
      noncompetitively at low ATP concentrations and competitively at high ATP
      concentrations the Na+/K+-activated hydrolysis of ATP under turnover conditions.
      It interacted preferentially with the low affinity ATP site as shown by its
      protective effect against the inactivation of Na+/K+-ATPase by Co(NH3)4ATP and
      Cr(H2O)4ATP. DANS-N3-ATP, however, inactivated Na+/K+-ATPase. The initial
      velocity of inactivation shows a sigmoid concentration dependence that was
      converted to a hyperbola in the presence of ATP. DANS-N3-ATP inhibited
      competitively the K+-activated hydrolysis of p-nitrophenyl phosphate in a
      fluorescein isothiocyanate-blocked enzyme but did not effect Na+-dependent
      phosphoenzyme formation from [gamma-32P]ATP in a Co(NH3)4PO4-blocked enzyme.
      These effects could be described by a Koshland-Nemethy-Filmer model assuming two
      nucleotide binding sites in strong cooperation. Fitting all data to this model
      revealed that ATP was bound in a negative cooperative way with a Kd = 0.3-1
      microM to the first site and a Kd = 100-120 microM to the second site of the
      enzyme containing already one ATP bound. The hydrolysis of ATP through a pathway
      with two ATP bound was 30 times faster than hydrolysis with one ATP bound. DANS
      N3-ATP bound in a positive cooperative way with a Kd = 500 +/- 100 microM to the
      first site and a Kd = 2.5 +/- 0.5 microM to the second site containing already
      one DANS-N3-ATP bound. Therefore, DANS-N3-ATP may be an useful affinity marker of
      the low affinity, regulatory ATP site.

PMID- 9195938
TI  - Analysis of small latent transforming growth factor-beta complex formation and
      dissociation by surface plasmon resonance. Absence of direct interaction with
      thrombospondins.
AB  - Transforming growth factor-beta (TGFbeta) is a pluripotent regulator of cell
      growth and differentiation. The growth factor is expressed as a latent complex
      that must be converted to an active form before interacting with its ubiquitous
      high affinity receptors. This conversion involves the release of the mature
      TGFbeta through disruption of the noncovalent interactions with its propeptide or
      latency associated protein (LAP). Complex formation or dissociation between LAP
      and TGFbeta plays a very important role in TGFbeta biological activity at
      different steps. To further characterize the kinetic parameters of this
      interaction, we have employed surface plasmon resonance biosensor methodology.
      Using this technique, we observed real time association of LAP with mature
      TGFbeta1. The complex formation showed an equilibrium Kd around 3-7 nM.
      Furthermore, we observed dissociation of the complex in the presence of extreme
      pH, chaotropic agents, or plasmin, confirming their effects on TGFbeta
      activation. The same approach was used to examine whether latent TGFbeta1 could
      interact with thrombospondins, previously described as activators of latent
      TGFbeta. Using this method, we could not detect any direct interaction of
      thrombospondins with either LAP alone, TGFbeta1 alone, or the small latent
      TGFbeta1 complex. This suggests that activation of latent TGFbeta1 complex by
      thrombospondins is through an indirect mechanism.

PMID- 9195937
TI  - Differential modulation of neuron survival during development by nerve growth
      factor binding to the p75 neurotrophin receptor.
AB  - Nerve growth factor (NGF) supports the survival and differentiation of distinct
      populations of peripheral and central neurons. NGF binds to two classes of cell
      surface receptors, the protein tyrosine kinase TrkA and the smaller p75 receptor
      lacking intrinsic catalytic activity. It has been suggested that both receptors
      are required for NGF high affinity binding, although TrkA appears to be
      sufficient for transducing most of the biological effects of NGF. Some evidence
      suggests that p75 could play a modulatory role on TrkA activation by an as yet
      unknown mechanism. In this study, we have investigated functional roles of p75
      using a purified triple mutant NGF (triNGF) deficient in p75 binding but
      retaining significant TrkA binding and activation. The mutant was found to be as
      potent as wild type NGF at promoting survival of serum-deprived TrkA-expressing
      fibroblasts. On developing chick sensory neurons, survival responses to mutant
      and native NGF were indistinguishable when assayed at nanomolar concentrations.
      However, triNGF was 3- to 4-fold less potent than wild type NGF at lower
      concentrations (i.e. 10(-11) M). Interestingly, in PC12 cells coexpressing TrkA
      and p75, no high affinity binding sites for triNGF could be detected. The reduced
      responsiveness to triNGF in sensory neurons was increasingly evident at later
      developmental stages; late embryonic neurons did not respond at all to
      concentrations of triNGF that were saturating at earlier developmental stages.
      Likewise, although no difference could be seen between wild type and mutant NGF
      on the survival responses of embryonic rat superior cervical ganglion sympathetic
      neurons, the mutant was much less potent than native NGF on postnatal sympathetic
      neurons. In sensory neurons, the decrease in responsiveness to triNGF correlated
      with a developmental reduction in the expression of both p75 and TrkA. Thus, NGF
      binding to p75 enhances responsiveness to ligand, particularly when this is
      present at limiting concentrations. During development, p75 modulates
      responsiveness to NGF so that binding to p75 becomes increasingly important in
      neurons undergoing a down-regulation of NGF receptors. These results support a
      ligand-dependent modulatory role for p75 in NGF-mediated neuron survival
      consistent with p75 functioning as a TrkA regulator and/or signaling receptor.

PMID- 9195939
TI  - Cloning, sequencing, characterization, and expression of an extracellular alpha
      amylase from the hyperthermophilic archaeon Pyrococcus furiosus in Escherichia
      coli and Bacillus subtilis.
AB  - A gene encoding a highly thermostable extracellular alpha-amylase from the
      hyperthermophilic archaeon Pyrococcus furiosus was identified. The gene was
      cloned, sequenced, and expressed in Escherichia coli and Bacillus subtilis. The
      gene is 1383 base pairs long and encodes a protein of 461 amino acids. The open
      reading frame of the gene was verified by microsequencing of the recombinant
      purified enzyme. The deduced amino acid sequence is 25 amino acids longer at the
      N terminus than that determined by sequencing of the purified protein, suggesting
      that a leader sequence is removed during transport of the enzyme across the
      membrane. The recombinant alpha-amylase was biochemically characterized and shows
      an activity optimum at pH 4.5, whereas the optimun temperature for enzymatic
      activity is close to 100 degrees C. alpha-Amylase shows sequence homology to the
      other known alpha-amylases and belongs to family 13 of glycosyl hydrolases. This
      extracellular alpha-amylase is not homologous to the subcellular alpha-amylase
      previously isolated from the same organism.

PMID- 9195940
TI  - Interaction of the regulatory and catalytic subunits of cAMP-dependent protein
      kinase. Electrostatic sites on the type Ialpha regulatory subunit.
AB  - Since a basic surface on the catalytic (C) subunit of cAMP-dependent protein
      kinase is important for binding to the regulatory (R) subunit, acidic residues in
      R were sought that might contribute to R-C interaction. Using differential
      labeling by a water-soluble carbodiimide (Buechler, T. A., and Taylor, S. S.
      (1990) Biochemistry 29, 1937-1943), seven specific carboxylates in RIalpha were
      identified that were protected from chemical modification in the holoenzyme; each
      was then replaced with Ala. Of these, rRI(E15A/E106A/D107A)), rRI(E105A),
      rRI(D140A), rRI(E143A), and rRI(D258A) all were defective in holoenzyme formation
      and define negative electrostatic surfaces on RIalpha. An additional conserved
      carboxylate, Glu101 in RIalpha and the equivalent, Glu99 in RIIalpha were mutated
      to Ala. Replacement of Glu101 had no effect while rRII(E99A) was very defective.
      RIalpha and RIIalpha thus differ in the molecular details of how they recognize
      C. Unlike wild-type RI, two additional mutants, rRI(D170A) and rRI(K242A),
      inhibited C-subunit stoichiometrically in the presence of cAMP and show increases
      in both on- and off-rates. Asp170, which contributes directly to the hydrogen
      bonding network in cAMP-binding site A, thus contributes also to holoenzyme
      stability.

PMID- 9195941
TI  - Interferon-gamma modulates a p53-independent apoptotic pathway and apoptosis
      related gene expression.
AB  - Interferon (IFN)-gamma increases the sensitivity of tumor cell lines, many of
      which are p53 mutants, to tumor necrosis factor-alpha-mediated and anti-Fas
      antibody-mediated cell death. To better understand the mechanism of IFN-gamma
      action in modulating the cell death response independently of p53 function, we
      analyzed the death of the human colon adenocarcinoma cell line, HT-29, following
      treatment with IFN-gamma and various cytotoxic agents. Here we show that IFN
      gamma modulates cell death by sensitizing the cells to killing by numerous pro
      apoptotic stimuli but not pro-necrotic stimuli. Furthermore, we show that select
      genes from several important apoptosis-related gene families are induced by IFN
      gamma, including the apoptosis-signaling receptors CD95 (Fas/APO-1) and TNFR 1
      and interleukin-1beta-converting enzyme (Ice) family members Ice, CPP32 (Yama,
      apopain), ICErel-II (TX, Ich-2), Mch-3 (ICE-LAP3, CMH-1), Mch-4, and Mch-5 (MACH,
      FLICE). Of the bcl-2 family members, IFN-gamma directly induced bak but notably
      not bax, which is activated by p53. The IFN-responsive transcriptional activator
      interferon regulatory factor-1 was also strongly induced and translocated into
      the nucleus following IFN-gamma treatment. We propose that IFN-gamma modulates a
      p53-independent apoptotic pathway by both directly and indirectly inducing select
      apoptosis-related genes.

PMID- 9195942
TI  - 7-Deaza-8-bromo-cyclic ADP-ribose, the first membrane-permeant, hydrolysis
      resistant cyclic ADP-ribose antagonist.
AB  - Cyclic ADP-ribose (cADPR) is a putative second messenger that has been
      demonstrated to mobilize Ca2+ in many cell types. Its postulated role as the
      endogenous regulator of ryanodine-sensitive Ca2+ release channels has been
      greatly supported by the advent and use of specific cADPR receptor antagonists
      such as 8-NH2-cADPR (Walseth, T. F., and Lee, H. C. (1993) Biochim. Biophys. Acta
      1178, 235-242). However, investigations of the role of cADPR in physiological
      responses, such as fertilization, stimulus-secretion coupling, and excitation
      contraction coupling, have been hindered by the susceptibility of cADPR receptor
      antagonists to hydrolysis and the need to introduce these molecules into cells by
      microinjection or patch clamp techniques. We have recently reported on the
      discovery of a poorly hydrolyzable analogue of cADPR, 7-deaza-cADPR (Bailey, V.
      C., Sethi, J. K., Fortt, S. M., Galione, A., and Potter, B. V. L. (1997) Chem.
      Biol. 4, 41-51) but this, like cADPR, is an agonist of ryanodine-sensitive Ca2+
      release channels. We therefore explored the possibility of combining antagonistic
      activity with that of hydrolytic resistance and now report on the biological
      properties of the first hydrolysis-resistant cADPR receptor antagonist, 7-deaza-8
      bromo-cADPR. In addition this compound has the advantage of being membrane
      permeable. Together these properties make this hybrid molecule the most powerful
      tool to date for studying cADPR-mediated Ca2+ signaling in intact cells.

PMID- 9195943
TI  - Expression of mixed lineage kinase-1 in pancreatic beta-cell lines at different
      stages of maturation and during embryonic pancreas development.
AB  - Events controlling differentiation to insulin-secreting beta-cells in the
      pancreas are not well understood, although beta-cells are thought to arise from
      pluripotent ductal precursor cells. To search for signaling proteins that might
      be involved in beta-cell maturation, we analyzed protein kinase expression in two
      developmentally and functionally distinct pancreatic beta-cell lines, RIN-5AH and
      RIN-A12, by reverse transcriptase polymerase chain reaction. A number of tyrosine
      and serine/threonine kinases were identified in both lines. One protein kinase,
      mixed lineage kinase-1 (MLK-1), was expressed at both the RNA and protein levels
      in RIN-5AH cells, which display an immature beta-cell phenotype, but was not
      detected in the more mature RIN-A12 cells. Furthermore, levels of MLK-1 mRNA and
      protein were increased after brief stimulation of RIN-5AH cells with either the
      differentiation inducer, sodium butyrate, or with serum after serum starvation.
      These increases in expression were independent of phenotypic markers such as
      insulin secretion or surface expression of major histocompatibility class I- and
      A2B5-reactive ganglioside. In addition, increases in MLK-1 expression in the
      stimulated RIN-5AH cells were accompanied by phosphorylation of MLK-1 on serine
      but not tyrosine. Antisense oligonucleotides to two distinct regions of MLK-1
      caused RIN-5AH cells, but not RIN-A12 cells, to adopt a highly undifferentiated
      morphology, with a reduction in DNA synthesis and MLK-1 protein levels and
      elevated glucagon mRNA levels, but with no effect on insulin mRNA. In an
      immunohistochemical survey of embryonic mouse tissues, we found that temporal
      expression of MLK-1 was regulated in a tissue-specific manner. In the embryonic
      pancreas, MLK-1 expression was evident in ductal cells from day 13 to 16 but was
      not detected in late stage gestation or neonatal pancreas. These data suggest
      that MLK-1 is regulated in immature pancreatic beta-cells and their ductal
      precursors at the level of functional maturity and may therefore play a role in
      beta-cell development.

PMID- 9195944
TI  - Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates
      anchorage-independent growth.
AB  - Caveolae are plasma membrane-attached vesicular organelles. Caveolin-1, a 21-24
      kDa integral membrane protein, is a principal component of caveolae membranes in
      vivo. Both caveolae and caveolin are most abundantly expressed in terminally
      differentiated cells: adipocytes, endothelial cells, and muscle cells.
      Conversely, caveolin-1 mRNA and protein expression are lost or reduced during
      cell transformation by activated oncogenes such as v-abl and H-ras (G12V);
      caveolae are absent from these cell lines. However, its remains unknown whether
      down-regulation of caveolin-1 protein and caveolae organelles contributes to
      their transformed phenotype. Here, we have expressed caveolin-1 in oncogenically
      transformed cells under the control of an inducible-expression system. Regulated
      induction of caveolin-1 expression was monitored by Western blot analysis and
      immunofluorescence microscopy. Our results indicate that caveolin-1 protein is
      expressed well using this system and correctly localizes to the plasma membrane.
      Induction of caveolin-1 expression in v-Abl-transformed and H-Ras (G12V)
      transformed NIH 3T3 cells abrogated the anchorage-independent growth of these
      cells in soft agar and resulted in the de novo formation of caveolae as seen by
      transmission electron microscopy. Consistent with its antagonism of Ras-mediated
      cell transformation, caveolin-1 expression dramatically inhibited both Ras/MAPK
      mediated and basal transcriptional activation of a mitogen-sensitive promoter.
      Using an established system to detect apoptotic cell death, it appears that the
      effects of caveolin-1 may, in part, be attributed to its ability to initiate
      apoptosis in rapidly dividing cells. In addition, we find that caveolin-1
      expression levels are reversibly down-regulated by two distinct oncogenic
      stimuli. Taken together, our results indicate that down-regulation of caveolin-1
      expression and caveolae organelles may be critical to maintaining the transformed
      phenotype in certain cell populations.

PMID- 9195946
TI  - Cloning and characterization of a novel integrin beta3 subunit.
AB  - We have identified a novel integrin beta3 subunit, termed beta3C, from a human
      osteoclast cDNA library. The COOH-terminal sequence and 3'-untranslated region of
      the beta3C subunit differs from the previously reported beta3A (platelet) and
      beta3B (placenta) sequences, while the regions coding for the transmembrane and
      extracellular domains are identical. The beta3C cytoplasmic domain contains 37
      amino acids, the last 17 of which are encoded by a novel exon located about 6
      kilobase pairs downstream of exon 14 of the beta3A gene. HEK 293 cells were
      stably co-transfected with alphaV and either beta3C (HEKbeta3C) or beta3A
      (HEKbeta3A). The viability of HEKbeta3C cells was lower than that of HEKbeta3A
      cells, and HEKbeta3C cells in culture grew as clusters rather than as a
      monolayer. The novel cytoplasmic domain did not affect receptor binding affinity;
      both alphaVbeta3A and alphaVbeta3C isoforms exhibited high affinity binding to
      125I-echistatin and cyclic and linear RGD peptides. However, in contrast to
      HEKbeta3A, HEKbeta3C cells failed to adhere to osteopontin, an alphaVbeta3 matrix
      protein. The data provide further support for the key role of the cytoplasmic
      domain of the beta3 integrin in cell adhesion and suggest a potential role for
      the beta3C integrin subunit in modulating cell-matrix interactions.

PMID- 9195945
TI  - Heparin-induced self-association of fibroblast growth factor-2. Evidence for two
      oligomerization processes.
AB  - Fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, requires heparin
      for dimerization and activation of the FGF receptor tyrosine kinase. The binding
      of multiple fibroblast growth factors by heparin may be necessary for
      dimerization of the FGF receptor. Analytical ultracentrifugation of FGF-2 in the
      presence of heparin-derived saccharides shows that both an active heparin
      octasaccharide and an inactive heparin-like disaccharide induce fibroblast growth
      factor-2 self-association. Analysis of the data indicates that the heparin
      octasaccharide induces a monomer-dimer-tetramer assembly of FGF-2 while the
      disaccharide induces a monomer-dimer equilibrium. Evidence is presented
      indicating that the dimer conformation induced by the heparin octasaccharide is a
      side by side dimer with the FGF-2 molecules cis to the heparin, while the
      disaccharide-induced dimer is a head to head dimer in which FGF-2 molecules are
      trans to the ligand. These results, combined with previous studies, support the
      model that formation of a specific side by side heparin-induced FGF-2 dimer is
      required for activation of the FGF receptor.

PMID- 9195947
TI  - The carboxyl-terminal sequence of the human secretory mucin, MUC6. Analysis Of
      the primary amino acid sequence.
AB  - The distribution of MUC6 suggests that its primary function is protection of
      vulnerable epithelial surfaces from damaging effects of constant exposure to a
      wide range of endogenous caustic or proteolytic agents. A combination of genomic,
      cDNA. and 3' rapid amplification of cDNA ends techniques was used to isolate the
      carboxyl-terminal end of MUC6. The 3' nontandem repeat region contained 1083 base
      pairs of coding sequence (361 amino acids) followed by 632 base pairs of 3'
      untranslated region. The coding sequence consists of two distinct regions; region
      1 contained the initial 270 amino acids (62% Ser-Thr-Pro with no Cys residues),
      and region 2 contained the COOH-terminal 91 amino acids (22% Ser-Thr-Pro with 12%
      Cys). Although region 1 had no homology to any sequences in GenBank, region 2 had
      approximately 25% amino acid homology to the COOH-terminal regions of human
      mucins MUC2, -5, and -5B and von Willebrand factor. The shortness of region 2
      would leave little of the peptide backbone exposed to a potentially hostile
      environment. Antibody studies suggest that MUC6 in its native form exists as a
      disulfide-bonded multimer. The conservation of the 11 cysteine positions in
      region 2 suggests the importance of this short region to mucin polymerization.

PMID- 9195948
TI  - Cloning, in vitro expression, and functional characterization of a novel human CC
      chemokine of the monocyte chemotactic protein (MCP) family (MCP-4) that binds and
      signals through the CC chemokine receptor 2B.
AB  - Here we describe the characterization of a novel human CC chemokine, tentatively
      named monocyte chemotactic protein (MCP-4). This chemokine was detected by random
      sequencing of expressed sequence tags in cDNA libraries. The full-length cDNA
      revealed an open reading frame for a 98-amino acid residue protein, and a
      sequence alignment with known CC chemokines showed high levels of similarity (59
      62%) with MCP-1, MCP-3, and eotaxin. MCP-4 cDNA was cloned into Drosophila S2
      cells, and the mature protein (residues 24-98) was purified from the conditioned
      medium. Recombinant MCP-4 induced a potent chemotactic response (EC50 = 2.88 +/-
      0.15 nM) and a transient rise in cytosolic calcium concentration in fresh human
      peripheral blood monocytes but not in neutrophils. Binding studies in monocytes
      showed that MCP-4 and MCP-3 were very potent in displacing high affinity binding
      of 125I-MCP-1 (IC50 for MCP-4, MCP-3, and unlabeled MCP-1 of 2.1 +/- 1.4, 0.85
      1.6, and 0.7 +/- 0.2 nM respectively), suggesting that all three chemokines
      interact with the CC chemokine receptor-2 (MCP-1 receptor). This was confirmed in
      binding studies with Chinese hamster ovary cells, stably transfected with the CC
      chemokine 2B receptor. Northern blot analysis in extracts of normal human tissues
      showed expression of mRNA for MCP-4 in small intestine, thymus, and colon, but
      the level of protein expression was too low to be detected in Western blot
      analysis. However, expression of MCP-4 protein was demonstrated by
      immunohistochemistry in human atherosclerotic lesion and found to be associated
      with endothelial cells and macrophages.

PMID- 9195949
TI  - Tyr624 and Tyr628 in insulin receptor substrate-2 mediate its association with
      the insulin receptor.
AB  - In addition to the pleckstrin homology domain and the phosphotyrosine binding
      domain in insulin receptor substrate (IRS)-1 and IRS-2, a region between amino
      acids 591 and 786 in IRS-2 (IRS-2-(591-786)) binds to the insulin receptor. Based
      on peptide competition studies, this region interacts with the phosphorylated
      regulatory loop of the insulin receptor; we designate this region the kinase
      regulatory loop binding (KRLB) domain. Two tyrosine residues in the KRLB domain
      at positions 624 and 628 are crucial for this interaction. Phosphorylation of
      tyrosine residues in the KRLB domain by the insulin receptor inhibits the binding
      to the receptor. These results reveal a novel mechanism regulating the
      interaction of the insulin receptor and IRS-2 that may distinguish the signal of
      IRS-2 from IRS-1.

PMID- 9195950
TI  - Characterization of two SHP-2-associated binding proteins and potential
      substrates in hematopoietic cells.
AB  - Multiple studies have demonstrated an important role for the Src homology 2
      containing tyrosine phosphatase 2 (SHP-2) in receptor tyrosine kinase-regulated
      cell proliferation and differentiation. Recent studies have identified potential
      SHP-2 substrates which mediate these effects. SHP-2 also is implicated in several
      cytokine receptor signaling pathways and in Bcr-Abl transformation. However, its
      precise role and targets in normal and abnormal hematopoietic cells remain to be
      determined. We identified two novel tyrosyl-phosphorylated proteins associated
      with SHP-2 in hematopoietic cells. The first, a 97-kDa cytosolic protein (p97),
      associates inducibly with SHP-2 upon cytokine stimulation and constitutively in
      Bcr-Abl-transformed cells. In contrast, p135, a 135-kDa transmembrane
      glycoprotein, forms a distinct complex with SHP-2, independent of cytokine
      stimulation or Bcr-Abl transformation. Far Western analysis reveals that SHP-2,
      via its Src homology 2 domains, can interact directly with either protein. In
      vitro dephosphorylation experiments, as well as transient transfection studies
      using wild type and mutant SHP-2 constructs, suggest that p97 and p135 also are
      SHP-2 substrates. Our results indicate that SHP-2 forms at least two separate
      complexes in hematopoietic cells and point to new potential SHP-2 targets.

PMID- 9195951
TI  - Identification and characterization of multiple osmotic response sequences in the
      human aldose reductase gene.
AB  - Aldose reductase (AR) has been implicated in osmoregulation in the kidney because
      it reduces glucose to sorbitol, which can serve as an osmolite. Under
      hyperosmotic stress, transcription of this gene is induced to increase the enzyme
      level. This mode of osmotic regulation of AR gene expression has been observed in
      a number of nonrenal cells as well, suggesting that this is a common response to
      hyperosmotic stress. We have identified a 132-base pair sequence approximately 1
      kilobase pairs upstream of the transcription start site of the AR gene that
      enhances the transcription activity of the AR promoter as well as that of the
      SV40 promoter when the cells are under hyperosmotic stress. Within this 132-base
      pair sequence, there are three sequences that resemble TonE, the tonicity
      response element of the canine betaine transporter gene, and the osmotic response
      element of the rabbit AR gene, suggesting that the mechanism of osmotic
      regulation of gene expression in these animals is similar. However, our data
      indicate that cooperative interaction among the three TonE-like sequences in the
      human AR may be necessary for their enhancer function.

PMID- 9195952
TI  - Cloning of a putative vesicle transport-related protein, RA410, from cultured rat
      astrocytes and its expression in ischemic rat brain.
AB  - To elucidate the role of astrocytes in the stress response of the central nervous
      system to ischemia, early gene expression was evaluated in cultured rat
      astrocytes subjected to hypoxia/reoxygenation. Using differential display, a
      novel putative vesicle transport-related factor (RA410) was cloned from
      reoxygenated astrocytes. Analysis of the deduced amino acid sequence showed RA410
      to be composed of domains common to vesicle transport-related proteins of the
      Sec1/Unc18 family, including Sly1p and Sec1p (yeast), Rop (Drosophila), Unc18
      (Caenorhabditis elegans), and Munc18 (mammalian), suggesting its possible role in
      vesicular transport. Northern analysis of normal rat tissues showed the highest
      expression of RA410 transcripts in testis. When astrocyte cultures were subjected
      to a period of hypoxia followed by reoxygenation, induction of RA410 mRNA was
      observed within 15 min of reoxygenation, reaching a maximum by 60 min. At the
      start of reoxygenation, the addition of diphenyl iodonium, an NADPH oxidase
      inhibitor, blocked in parallel astrocyte generation of reactive oxygen
      intermediates and expression of RA410 message. In contrast, cycloheximide did not
      affect RA410 mRNA levels, indicating that RA410 is an immediate-early gene in the
      setting of reoxygenation. Using polyclonal antibody raised against an RA410
      derived synthetic peptide, Western blotting of lysates from reoxygenated
      astrocytes displayed an immunoreactive band of approximately 70 kDa, the
      expression of which followed induction of the mRNA. Fractionation of astrocyte
      lysates on sucrose gradients showed RA410 antigen to be predominantly in the
      plasma membrane. Immunoelectron microscopic analysis demonstrated RA410 in large
      vesicles associated with the Golgi, but not in the Golgi apparatus itself,
      consistent with its participation in post-Golgi transport. Consistent with these
      in vitro data, RA410 expression was observed in rat brain astrocytes following
      transient occlusion of the middle cerebral artery. These data provide insight
      into a new protein (RA410) that participates in the ischemia-related stress
      response in astrocytes.

PMID- 9195953
TI  - Phosphatidylinositol 3-kinase-dependent activation of protein kinase C-zeta in
      bacterial lipopolysaccharide-treated human monocytes.
AB  - The isoform identity of activated protein kinase C (PKC) and its regulation were
      investigated in bacterial lipopolysaccharide (LPS)-treated human monocytes.
      Resolution of detergent-soluble lysates prepared from LPS-treated, peripheral
      blood monocytes using Mono Q anion-exchange chromatography revealed two principal
      peaks of myelin basic protein kinase activity. Immunoblotting and
      immunoprecipitation with isoform-specific anti-PKC antibodies showed that the
      major and latest eluting peak is accounted for by PKC-zeta. In addition to
      primary monocytes, activation of PKC-zeta in response to LPS was also observed in
      the human promonocytic cell lines, U937 and THP-1. Consistent with its identity
      as PKC-zeta, the kinase did not depend upon the presence of lipids, Ca2+, or
      diacylglycerol for activity. In addition, the kinase phosphorylates peptide
      epsilon and myelin basic protein with equal efficiency but phosphorylates
      Kemptide and protamine sulfate poorly. Translocation of PKC-zeta from the
      cytosolic to the particulate membrane fraction upon exposure of monocytes to LPS
      provided further evidence for activation of the kinase. Preincubation of
      monocytes with the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors,
      wortmannin or LY294002, abrogated LPS-induced activation of PKC-zeta.
      Furthermore, activation of PKC-zeta failed to occur in U937 cells transfected
      with a dominant negative mutant of the p85 subunit of PI 3-kinase. PKC-zeta
      activity was also observed to be enhanced in vitro by the addition of
      phosphatidylinositol 3,4,5P3. These findings are consistent with a model in which
      PKC-zeta is activated downstream of PI 3-kinase in monocytes in response to LPS.

PMID- 9195954
TI  - Identification of transcription factor binding sites important in the regulation
      of the human interleukin-5 gene.
AB  - This study identifies three regions of the human interleukin (IL)-5 promoter
      involved in binding nuclear factors from activated T cells. DNase I footprinting
      and mobility shift assays with nuclear proteins from the human T cell clone, SP
      B21, demonstrated protein interactions with each of these response elements
      (REs), located between positions -79 and -45 (RE-I), -123 and -92 (RE-II), and 
      170 and -130 (RE-III). Two of these regions, RE-II and RE-III, have not
      previously been described to regulate IL-5 expression in T cells. The RE-II site
      was shown to be critical for inducible IL-5 promoter activity in transient
      transfection assays in D10.G4.1 T cells, while the RE-III site functions as a
      negative regulatory element. The activity of the RE-II site was specifically
      inhibited by cyclosporin A, and transfection assays with IL-5 constructs
      containing mutations in the RE-II site showed greatly reduced reporter gene
      activity. We have defined the sequence involved in stimulation-dependent
      transcription and have identified constitutive as well as inducible DNA-binding
      protein complexes that bind to RE-II. Antibodies against at least two members of
      the nuclear factor of activated T cells (NFAT) family of transcription factors
      are capable of binding to the IL-5 RE-II complexes, although they can be
      distinguished from previously identified NFAT-specific complexes by several
      characteristics.

PMID- 9195955
TI  - Factors determining the specificity of signal transduction by guanine nucleotide
      binding protein-coupled receptors. Integration of stimulatory and inhibitory
      input to the effector adenylyl cyclase.
AB  - To define the integration of multiple signals by different types of adenylyl
      cyclase (AC) within the cell, we altered the population of enzymes expressed in
      the cell and determined the subsequent processing of stimulatory and inhibitory
      input. DDT1-MF2 cells expressed AC VI-IX and were stably transfected with AC II,
      III, or IV. Enzyme expression was confirmed by RNA blot analysis and functional
      assays. Basal enzyme activity was only increased in AC II transfectants (6-fold).
      Maximum stimulation of enzyme activity was increased in each of the AC
      transfectants to varying extents. alpha2A/D-AR activation elicited enzyme type
      specific responses. alpha2-AR activation inhibited the effect of isoproterenol in
      control transfectants, and this action was magnified in AC III transfectants. In
      AC II and AC IV transfectants, alpha2-AR activation initiated both positive
      (Gbetagamma) and negative signals (Gialpha) to the Gsalpha-stimulated enzyme, and
      both types of signals were blocked by cell pretreatment with pertussis toxin. The
      negative input to AC II from the alpha2-AR was blocked by protein kinase C
      activation in AC II transfectants, but it was the positive input to AC IV that
      was compromised by protein kinase C activation. These data indicate that the
      integration of multiple signals by adenylyl cyclases is a dynamic process
      depending upon the enzyme type and phosphorylation status.

PMID- 9195956
TI  - Selective involvement of ceramide in cytokine-induced apoptosis. Ceramide
      inhibits phorbol ester activation of nuclear factor kappaB.
AB  - Among its diverse biologic effects, the cytokine tumor necrosis factor alpha
      causes the rapid nuclear translocation of the transcription factor, nuclear
      factor kappaB (NF-kappaB). The p55 tumor necrosis factor (TNF) receptor shares
      with the related APO-1/Fas antigen the ability to initiate apoptosis. We
      investigated the role of the sphingolipid mediator ceramide in the cytokine
      induced signaling mechanisms leading to NF-kappaB activation and cell death.
      Several lines of evidence presented here suggest that ceramide generated in
      response to TNFalpha or Fas activation is not involved in NF-kappaB activation.
      (i) Cell-permeable ceramides and exogenous sphingomyelinase failed to induce
      either nuclear translocation of NF-kappaB or degradation of its cytosolic
      inhibitor, I-kappaB, in Jurkat T cells. (ii) Ceramide treatment of cells
      inhibited phorbol ester-induced activation of NF-kappaB. (iii) TNFalpha potently
      activated NF-kappaB in a cell line deficient in acid sphingomyelinase. (iv)
      TNFalpha activated NF-kappaB within minutes without altering ceramide levels. (v)
      Treatment of Jurkat cells with cross-linking antibodies to APO-1/Fas induced
      large scale increases in ceramide and apoptosis without affecting NF-kappaB. (vi)
      Ceramide generation in response to Fas activation was inhibited by N
      acetyltyrosinylvalinylalanylaspartyl chloromethyl ketone, a peptide inhibitor of
      interleukin-1beta-converting enzyme-like proteases, whereas TNFalpha-induced NF
      kappaB activation was unaffected by the inhibitor. These results show that
      ceramide accumulation belongs selectively to the apoptotic pathway(s) induced by
      cytokines, and, if anything, ceramide may participate in negative feedback
      regulation of NF-kappaB.

PMID- 9195957
TI  - The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-binding
      protein.
AB  - The hepatitis B virus X protein induces transcriptional activation of a wide
      variety of viral and cellular genes. In addition to its ability to interact
      directly with many nuclear transcription factors, several reports indicate that
      the X protein stimulates different cytoplasmic kinase signal cascades. Using the
      yeast two-hybrid screen, we have isolated a clone designated X-associated protein
      3 (XAP3) that encodes a human homolog of the rat protein kinase C-binding
      protein. One of the activation domains of X (amino acids 90-122) is required for
      binding to XAP3, while the NH2-terminal part of XAP3 is necessary for binding to
      X. Both X and XAP3 bound specifically to the eta PKC isoenzyme synthesized in
      rabbit reticulocyte lysates. Overexpression of XAP3 enhanced X transactivation
      activity. These results support earlier findings that one of the mechanisms of
      transactivation by X is through involvement with the cellular protein kinase C
      pathway.

PMID- 9195958
TI  - hMAF, a small human transcription factor that heterodimerizes specifically with
      Nrf1 and Nrf2.
AB  - A 1.6-kilobase pair full-length cDNA encoding a transcription factor homologous
      to the Maf family of proteins was isolated by screening a K562 cDNA library with
      the NFE2 tandem repeat probe derived from the globin locus control region. The
      protein, which was designated hMAF, contains a basic DNA binding domain and an
      extended leucine zipper but lacks any recognizable activation domain. Expressed
      in vitro, the hMAF protein is able to homodimerize in solution and band-shift the
      NFE2 tandem repeat probe. In addition to homodimers, hMAF can also form high
      affinity heterodimers with two members of the NFE2/CNC-bZip family (Nrf1 and
      Nrf2) but not with a third family member, p45-NFE2. Although hMAF/hMAF homodimers
      and hMAF/Nrf1 and hMAF/Nrf2 heterodimers bind to the same NFE2 site, they exert
      functionally opposite effects on the activity of a linked gamma-globin gene. In
      fact, whereas all hMAF/CNC-bZip heterodimers stimulate the activity of a gamma
      promoter reporter construct in K562 cells, the association into homodimers that
      is induced by overexpressing hMAF inhibits the activity of the same construct.
      Thus variations in the expression of hMAF may account for the modulation in the
      activity of the genes that bear NFE2 recognition sites.

PMID- 9195959
TI  - Characterization and functional analysis of the promoter of RAGE, the receptor
      for advanced glycation end products.
AB  - The receptor for advanced glycation end products, RAGE, is a member of the
      immunoglobulin superfamily of cell surface molecules differentially expressed on
      a range of cell types. Ligation of RAGE perturbs homeostatic mechanisms and,
      potentially, provides a basis for cellular dysfunction in pathologic situations
      in which its ligands accumulate. To understand factors underlying RAGE
      expression, we cloned the 5'-flanking region of the RAGE gene and characterized
      putative regulatory motifs. Analysis of the putative promoter region revealed the
      presence of three potential NF-kappaB-like and two SP1 binding sites. Transient
      transfection of vascular endothelial and smooth muscle cells using chimeric 5'
      deletion constructs linked to luciferase reporter revealed that the region -1543/
      587 contributed importantly to both basal and stimulated expression of the RAGE
      gene. This region of the RAGE gene contained three putative NF-kappaB-like
      binding sites and was responsible for increased luciferase activity observed when
      endothelial or smooth muscle cells were stimulated with lipopolysaccharide. DNase
      I footprinting assays and electrophoretic mobility shift assay revealed that two
      of the three NF-kappaB-like binding sites (1 and 2) were likely functional and
      responsive to stimuli. Upon simultaneous mutation of NF-kappaB-like sites 1 and
      2, both basal promoter expression and response to stimulation with LPS, as
      measured by relative luciferase activity, were significantly diminished. These
      results point to NF-kappaB-dependent mechanisms regulating cellular expression of
      RAGE and suggest a means of linking RAGE to the inflammatory response.

PMID- 9195960
TI  - A distinct function of STAT proteins in erythropoietin signal transduction.
AB  - The Janus kinase (JAK)-signal transducers and activators of transcription (STAT)
      pathway is an important signaling pathway of interferons and cytokines. We
      examined the activation of STAT proteins induced by interleukin-3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), or erythropoietin
      (EPO) using the human leukemia cell line, UT-7, which requires these cytokines
      for growth. IL-3, GM-CSF, and EPO induced DNA-binding activity to the
      oligonucleotides corresponding to the sis-inducible elements (SIE) of c-fos, in
      addition to the beta-casein promoter (beta-CAP), SIE- and beta-CAP-binding
      proteins were identical to Stat1alpha and Stat3 complex and to Stat5 protein,
      respectively. This indicates that IL-3, GM-CSF, and EPO commonly activated
      Stat1alpha, Stat3, and Stat5 proteins in UT-7. However, EPO hardly activated
      Stat1alpha and Stat3 in UT-7/GM, which is a subline of UT-7 that grows slightly
      in response to EPO. Transfection studies revealed that UT-7/GM cells
      constitutively expressing Stat1alpha, but not Stat3, can grow as well in response
      to EPO as GM-CSF, suggesting that Stat1alpha is involved in the EPO-induced
      proliferation of UT-7. Thus, although Stat1alpha, Stat3, and Stat5 proteins are
      activated by GM-CSF, IL-3, and EPO, our data suggest that each STAT protein has a
      distinctive role in the actions of cytokines.

PMID- 9195961
TI  - Membrane-associated insulin-like growth factor-binding protein-3 inhibits insulin
      like growth factor-I-induced insulin-like growth factor-I receptor signaling in
      ishikawa endometrial cancer cells.
AB  - The function of cell surface-associated insulin-like growth factor-binding
      proteins (IGFBPs) is controversial. Both inhibition and facilitation of IGF
      action as well as IGF-independent effects have been reported. We examined the
      influence of endogenous cell surface-associated IGFBPs on IGF-I receptor (IGF-IR)
      function in Ishikawa endometrial cancer cells by comparing the effects of IGF-I
      and its truncated analog des-(1-3)-IGF-I on several components of the IGF-IR
      signal transduction pathway in the absence of significant amounts of soluble
      IGFBPs. IGF-I and des-(1-3)-IGF-I are known to have similar affinities for IGF
      IR, although the affinity of des-(1-3)-IGF-I for IGFBPs is greatly reduced. Here
      we show that the two ligands were equipotent not only in IGF-IR binding but also
      in receptor activation in NIH 3T3 cells overexpressing IGF-IR and possessing a
      relatively small number of cell surface-associated IGFBPs. In contrast, des-(1-3)
      IGF-I manifested a remarkably higher potency as compared with IGF-I in inducing
      short and middle term cellular responses in IGF-IR-transfected Ishikawa
      endometrial cancer cells possessing a high number of both the receptor and the
      cell membrane-bound IGFBP-3. Thus, this difference in the effects of IGF-I and
      des-(1-3)-IGF-I can be attributed to the attenuation of IGF-I-mediated IGF-IR
      signaling by membrane-bound IGFBP-3.

PMID- 9195962
TI  - Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for
      the HEK receptor.
AB  - HEK is a member of the EPH-like receptor tyrosine kinase family, which appear to
      have roles in development and oncogenesis. Recently, we purified a soluble HEK
      ligand which is also a ligand (AL1) for the HEK-related receptor EHK1.
      Promiscuity appears to be a characteristic feature of interactions between the
      EPH-like receptors and their ligands, termed ligands for EPH-related kinases
      (LERKs). This prompted us to analyze the interactions between the HEK exodomain
      and fusion proteins comprising candidate LERKs and the Fc portion of human IgG1
      (Fc) or a FLAGTM-peptide tag by surface plasmon resonance, size exclusion high
      performance liquid chromatography, sedimentation equilibrium, and
      transphosphorylation. Our results indicate that AL1/LERK7 is the preferred high
      affinity ligand for HEK, forming a stable 1:1 complex with a dissociation
      constant of 12 nM. As expected the apparent affinities of bivalent fusion
      proteins of LERKs and the Fc portion of human IgG1 had significantly reduced
      dissociation rates compared with their monovalent, FLAGTM-tagged derivatives.
      High-avidity binding of monovalent ligands can be achieved by antibody-mediated
      cross-linking of monovalent ligands and with LERK7 results in specific
      phosphorylation of the receptor. By extrapolation, our findings indicate that
      some of the reported LERK-receptor interactions are a consequence of the use of
      bivalent ligand or receptor constructs and may be functionally irrelevant.

PMID- 9195963
TI  - The position dependence of translational regulation via RNA-RNA and RNA-protein
      interactions in the 5'-untranslated region of eukaryotic mRNA is a function of
      the thermodynamic competence of 40 S ribosomes in translational initiation.
AB  - Cap proximity is a requirement to enable secondary structures and RNA-binding
      proteins to repress translational initiation via the 5'-untranslated region (5'
      UTR) of mammalian mRNAs. We show that in Saccharomyces cerevisiae, unlike
      mammalian cells, the in vitro translational repressive effect of the mammalian
      iron regulatory protein 1 (IRP1) is independent of the site of its target in the
      5'-UTR, the iron-responsive element (IRE). In vitro studies demonstrate that the
      binding affinity of IRP1 is also unaffected by the position of the IRE. Using IRE
      loop mutants, we observe an almost complete loss of IRP1-dependent repression in
      yeast concomitant with a 150-fold reduction in binding affinity for the IRE
      target. This mirrors the natural quantitative range of iron-induced adjustment of
      IRE/IRP1 affinity in mammalian cells. By enhancing the stability of the IRE stem
      loop, we also show that its intrinsic folding energy acts together with the
      binding energy of IRP1 to give an additive capacity to restrict translational
      initiation. An IRE.IRP1 complex in a cap-distal position in yeast blocks scanning
      40 S ribosomes on the 5'-UTR. It follows that the position effect of mammalian
      site-specific translational repression is dictated by the competence of the
      mammalian preinitiation complex to destabilize inhibitory structures at different
      steps of the initiation process.

PMID- 9195964
TI  - Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis.
AB  - Sp1 nuclear levels have been shown to directly correlate with the proliferative
      state of the cell. We therefore studied changes in the abundance of Sp1 in a rat
      pituitary cell line GH4 whose growth rate is regulated by epidermal growth factor
      (EGF). Nuclear extracts from GH4 cells treated with 10 nM EGF for at least 16 h
      showed a 50% decrease in Sp1 binding to a GC-rich element present in the gastrin
      promoter. The decrease in binding correlated with a decrease in cell
      proliferation, a loss of nuclear Sp1 protein and a 50-60% decrease in Sp1
      mediated transactivation through an Sp1 enhancer element in transfection assays.
      Okadaic acid, a phosphatase inhibitor, was synergistic with the effect of EGF on
      Sp1 protein levels suggesting that the loss of Sp1 was mediated by
      phosphorylation events. This result was confirmed by showing a 2-fold increase in
      orthophosphate-labeled Sp1 with EGF and okadaic acid. Cycloheximide prevented the
      expected loss of Sp1 mediated by EGF and okadaic acid suggesting that the
      synthesis of a protease may mediate these events. This hypothesis was tested
      directly by showing that the cysteine protease inhibitor leupeptin prevented Sp1
      degradation. Using the PEST-FIND computer program, the computed PEST score for
      human and rat Sp1 is 10.4 and 13.7, respectively, indicating that Sp1 has a
      domain with a high concentration of proline, glutamic acid, serine, and threonine
      residues as reported for a number of proteins with inducible rates of
      degradation. Collectively, these results indicate that sustained stimulation of
      GH4 cells by EGF initiates a cascade of phosphorylation events that promotes Sp1
      proteolysis, decreased Sp1 nuclear levels and decreased cellular proliferation.

PMID- 9195965
TI  - Cloning and functional characterization of a rat renal organic cation transporter
      isoform (rOCT1A).
AB  - Polyspecific organic cation transporters in the renal proximal tubule mediate the
      secretion of many clinically used drugs as well as endogenous metabolites.
      Recently, two organic cation transporters (rOCT1 and rOCT2) were cloned from rat
      kidney. In this study, we report the cloning and functional expression of an
      rOCT1 isoform, rOCT1A, from rat kidney. Genomic DNA cloning and sequencing
      demonstrated that rOCT1A is an alternatively spliced variant of rOCT1 with a
      deletion of 104 base pairs near the 5'-end. The uptake of [14C]tetraethylammonium
      (TEA) in oocytes injected with the cRNA-encoding rOCT1A was increased 16-fold
      over that in water-injected oocytes (29 +/- 2.8 pmol/oocyte/h versus 1.8 +/- 0.13
      pmol/oocyte/h, mean +/- S.E., p < 0.05). [14C]TEA uptake in the cRNA-injected
      oocytes was saturable (Km = 42 +/- 11 microM) and was inhibited significantly by
      organic cations, including cimetidine and N1-methylnicotinamide. The amino acid
      sequence was deduced from the cDNA after examination of all three reading frames.
      Two overlapping open reading frames were found. Studies with synthetic constructs
      suggest that a functional organic cation transporter is encoded by the larger
      open reading frame. The larger open reading frame encodes a 430-amino acid
      protein (termed rOCT1A) that is 92% identical to rOCT1 and 57% identical to
      rOCT2. From hydropathy analysis, rOCT1A is predicted to have 10 transmembrane
      domains with both amino and carboxyl termini intracellular. RNase protection
      assays demonstrate the presence of rOCT1A mRNA transcripts in rat kidney cortex,
      medulla, and intestine. These studies demonstrate the presence of a functional,
      alternatively spliced organic cation transporter (rOCT1A) in rat kidney.

PMID- 9195966
TI  - A mono-functional 3-deoxy-D-manno-octulosonic acid (Kdo) transferase and a Kdo
      kinase in extracts of Haemophilus influenzae.
AB  - Lipopolysaccharide of Haemophilus influenzae contains a single 3-deoxy-D-manno
      octulosonic acid (Kdo) residue, linked to the 6' position of lipid A. In
      Escherichia coli and related organisms, a Kdo disaccharide is attached to lipid
      A. In previous studies, we cloned the gene (kdtA) encoding the E. coli Kdo
      transferase and demonstrated that homogeneous preparations of KdtA polypeptide
      catalyzed the attachment of both Kdo groups to the precursor, lipid IVA. E. coli
      KdtA produced only traces of mono-glycosylated product. We now show that a single
      Kdo is transferred to lipid IVA in extracts of H. influenzae. The mono-functional
      Kdo transferase of H. influenzae is membrane-bound, and the reaction is dependent
      upon a CMP-Kdo-generating system, as in E. coli. The specific activity of Kdo
      transfer to lipid IVA is 0.5-1 nmol/min/mg in H. influenzae membranes. Utilizing
      solubilized H. influenzae membranes, milligram quantities of Kdo-lipid IVA were
      prepared for analysis. Matrix-assisted laser desorption/ionization mass
      spectrometry revealed a parent ion (M - H)- at m/z 1626.0, consistent with the
      addition of a single Kdo moiety. Like lipid IVA, Kdo-lipid IVA was an excellent
      substrate for the bi-functional Kdo transferase of E. coli. In membranes of H.
      influenzae, but not E. coli, Kdo-lipid IVA was further phosphorylated in the
      presence of ATP, yielding a mono-phosphorylated Kdo-lipid IVA with a parent ion
      (M - H)- at m/z 1703.9. The identification of the mono-functional H. influenzae
      Kdo transferase, which is encoded by a KdtA homologue that displays 50% identity
      to its E. coli counterpart, should facilitate the mechanistic dissection of more
      complex multi-functional Kdo transferases, like those of E. coli and Chlamydia
      trachomatis.

PMID- 9195967
TI  - Coexistence of two beta subunit isoforms in the same gamma-aminobutyric acid type
      A receptor.
AB  - Three novel subunit-specific antisera to the beta1, beta2, and beta3 subunits of
      rat gamma-aminobutyric acid type A (GABAA) receptors have been used to study the
      native receptor in the rat brain. Affinity-purified anti-beta1, anti-beta2, and
      anti-beta3 antibodies recognized in immunoblots protein bands of 57, 55, and 57
      kDa, respectively. Quantitative immunoprecipitation of solubilized GABAA
      receptors from various rat brain regions showed that the beta2 subunit was the
      most abundant isoform in cerebellum (in 96% of the GABAA receptors) and cerebral
      cortex (64%) but that it was the least abundant isoform in hippocampus (44%). The
      beta3 subunit was found most abundant in hippocampus (64%) followed by cerebral
      cortex (48%) and cerebellum (33%). The beta1 subunit was present in a very small
      proportion of the cerebellar GABAA receptors (3%), but it was present in a high
      proportion of the GABAA receptors from the hippocampus (49%) and cerebral cortex
      (32%). Quantitative receptor immunoprecipitation or immunopurification followed
      by immunoblotting experiments have revealed the existence of colocalization of
      two different beta subunit isoforms in a significant proportion of the brain
      GABAA receptors. Thus, in the rat cerebral cortex 33% of the GABAA receptors have
      both beta2 and beta3 subunits, and 19% of the receptors have both beta1 and beta3
      subunits. The extent of colocalization of beta subunit isoforms varied among
      brain regions, being highest in hippocampus and lowest in cerebellum. These and
      other results taken together suggest that the number of alpha, beta, and gamma
      subunits (stoichiometry) in the brain GABAA receptor pentamers might not be
      unique. It might vary depending on receptor type.

PMID- 9195968
TI  - Reconstitution of Monomethylamine:Coenzyme M methyl transfer with a corrinoid
      protein and two methyltransferases purified from Methanosarcina barkeri.
AB  - Methanogenesis from methylamines requires the intermediate methylation of 2
      mercaptoethanesulfonate (CoM). In vitro reconstitution of CoM methylation with
      monomethylamine was achieved with three purified proteins: a monomethylamine
      corrinoid protein (MMCP), the "A" isozyme of methylcobamide:CoM methyltransferase
      (MT2-A), and a newly isolated protein termed monomethylamine methyltransferase
      (MMAMT).MMAMT is a 170-kDa protein with 52-kDa subunits. The MMAMT polypeptide
      was rate-limiting for methyl transfer until at a 2-fold molar excess over MMCP.
      MMAMT is a monomethylamine:MMCP methyltransferase, since methylation of MMCP
      required MMAMT but not MT2-A. MMCP and MMAMT formed a complex detectable by size
      exclusion high pressure liquid chromatography. Methyl group transfer from methyl
      MMCP to CoM was mediated by MT2-A, since methyl iodide:CoM methyl transfer by
      MMCP and MT2-A did not require MMAMT. MT2-M, an isozyme of MT2-A, was inactive in
      MMCP-dependent methyl transfer. Immunodepletion of MMCP from the extract
      inhibited CoM methylation with monomethylamine but not dimethylamine. Purified
      MMCP reconstituted activity in immunodepleted extracts. These results show that
      MMCP is the major corrinoid protein for methanogenesis from monomethylamine
      detectable in extracts and that it interacts with two methyltransferases. MMAMT
      functions as a MMA:MMCP methyltransferase, while MT2-A functions as a methyl
      MMCP:CoM methyltransferase.

PMID- 9195969
TI  - Phosphorylation of Sendai virus phosphoprotein by cellular protein kinase C zeta.
AB  - The phosphoproteins (P) of nonsegmented negative strand RNA viruses are viral RNA
      polymerase subunits involved in both transcription and replication during the
      virus life cycle. Phosphorylation of P proteins in several negative strand RNA
      viruses by specific cellular kinases was found to be required for P protein
      function. In the present study, using bacterially expressed unphosphorylated P
      protein of Sendai virus, a mouse parainfluenza virus, we have shown that the
      major cellular kinase that phosphorylates P protein in vitro is biochemically and
      immunologically indistinguishable from protein kinase C (PKC) zeta isoform. PKC
      zeta was packaged into the Sendai virion and remained associated with purified
      viral ribonucleoprotein, where it phosphorylated both the P and the nucleocapsid
      protein in vitro. When PKC zeta-specific inhibitory pseudosubstrate peptide was
      introduced into LLC-MK2 cells prior to Sendai virus infection, production of
      progeny virus was dramatically attenuated, and kinetic analysis revealed that
      primary transcription was repressed. These data indicate that phosphorylation of
      the Sendai virus P protein by PKC zeta plays a critical role in the virus life
      cycle.

PMID- 9195970
TI  - Interferon-gamma rapidly increases peptide transporter (TAP) subunit expression
      and peptide transport capacity in endothelial cells.
AB  - Human cytotoxic T lymphocytes (CTL) recognize specific complexes of HLA class I
      molecules and peptides, which assemble when nascent class I molecules bind
      peptides transported from the cytoplasm into the endoplasmic reticulum by the
      heterodimeric transporter associated with antigen processing (TAP). Increased
      class I molecule expression on the cell surface increases the efficiency of CTL
      lysis. The kinetics of interferon (IFN)-gamma induction of TAP, peptide transport
      capacity, and HLA class I molecule expression was determined in endothelial
      cells, which are targets of CTL following transplantation or viral infection. TAP
      mRNAs are induced rapidly, increasing 20-fold (TAP1) or 10-fold (TAP2) by 12 h,
      whereas HLA class I mRNA is induced more slowly, increasing 10-fold in 24 h. TAP1
      and TAP2 proteins are also induced rapidly, increasing 10-fold in 24 h, whereas
      HLA class I heavy chain proteins and surface expression increase more slowly.
      Peptide transport capacity in endothelial and HeLa cells increases within 6 h of
      IFN-gamma treatment, suggesting that the IFN-gamma-induced TAP heterodimers are
      functional. Therefore, the IFN-gamma-induced increase in TAP proteins is
      accompanied by an increased peptide transport capacity, which may be important in
      supporting the subsequent rise in HLA class I protein expression.

PMID- 9195971
TI  - Conserved alpha-helical segments on yeast homologs of the synaptobrevin/VAMP
      family of v-SNAREs mediate exocytic function.
AB  - We are studying yeast homologs of the synaptobrevin/VAMP family of vesicle
      associated membrane proteins, which act as vesicular compartment-soluble N
      ethylmaleimide-sensitive factor attachment protein receptors (v-SNAREs) in cells
      having a capacity for stimulus-coupled secretion, as well as in other cell types.
      The yeast homologs, Snc1 and Snc2, localize to secretory vesicles and are
      required for normal bulk secretion in Saccharomyces cerevisiae. Here we have used
      Snc deletion mutants and chimeric Snc-VAMP proteins to demonstrate that these v
      SNAREs can be dissected into regions that are either indispensable or dispensable
      for exocytic function in vivo. We have found that a region encompassing two
      predicted amphipathic alpha-helices (helix 1 and helix 2) (residues 32-85), which
      are thought to form coiled-coil structures, is essential for conferring
      exocytosis in yeast. Deletions in either the helix 1 or helix 2 segments result
      in a complete loss in the ability of the protein to confer secretion competence
      to snc cells and to interact genetically with components of the proposed fusion
      complex: the Sec9 and Sso2 t-SNAREs and the Sec17 alpha-SNAP homolog. In
      contrast, deletions in either the variable (residues 2-27) or putative
      intravesicular (residues 115-117) regions have no deleterious effect upon v-SNARE
      function. This makes it unlikely that sequences in either the amino or carboxyl
      terminus act in an exocytic capacity. Along with additional studies utilizing
      chimeric Snc-VAMP proteins, we suggest that although the Snc and
      synaptobrevin/VAMP proteins have evolved to mediate vastly different exocytic
      programs, their structural requirements and actions have remained remarkably well
      conserved in evolution.

PMID- 9195972
TI  - The rat D4 dopamine receptor couples to cone transducin (Galphat2) to inhibit
      forskolin-stimulated cAMP accumulation.
AB  - Based on its expression pattern and pharmacology, the D4 dopamine receptor may
      play a role in schizophrenia. Thus it is of interest to know what signaling
      pathways are utilized by this receptor. Previously, we showed that activation of
      D4 receptors in a mouse mesencephalic neuronal cell line (MN9D) inhibited
      forskolin-stimulated cAMP accumulation in a pertussis toxin-sensitive (Ptx
      sensitive) fashion. Of the known Ptx-sensitive G-protein alpha subunits, MN9D
      expressed Galphai2, GalphaoA, and GalphaoB; however, none of these coupled to the
      D4 receptor. Using a low stringency polymerase chain reaction cloning method, we
      found an additional Ptx-sensitive G-protein cone transducin (Galphat2) expressed
      in the MN9D cells. We also found that Galphat2 mRNA is highly expressed in rat
      mesencephalic tissue. To test the hypothesis that the D4 receptor couples to
      Galphat2, we cotransfected MN9D cells with the D4 receptor and a mutagenized Ptx
      resistant Galphat2 subunit (mGalphat2). Application of the dopaminergic agonist
      quinpirole to cotransfected cells inhibited forskolin-stimulated cAMP
      accumulation in the presence or absence of Ptx. To our knowledge, this is the
      first report demonstrating that the D4 dopamine receptor functionally couples to
      a specific G-protein and that a non-opsin-like receptor can couple with a
      transducin subunit.

PMID- 9195973
TI  - Distinguishing the specificities of closely related proteases. Role of P3 in
      substrate and inhibitor discrimination between tissue-type plasminogen activator
      and urokinase.
AB  - Elucidating subtle specificity differences between closely related enzymes is a
      fundamental challenge for both enzymology and drug design. We have addressed this
      issue for two intimately related serine proteases, tissue-type plasminogen
      activator (t-PA) and urokinase-type plasminogen activator (u-PA), by modifying
      the technique of substrate phage display to create substrate subtraction
      libraries. Characterization of individual members of the substrate subtraction
      library accomplished the rapid, direct identification of small, highly selective
      substrates for t-PA. Comparison of the amino acid sequences of these selective
      substrates with the consensus sequence for optimal substrates for t-PA, derived
      using standard substrate phage display protocols, suggested that the P3 and P4
      residues are the primary determinants of the ability of a substrate to
      discriminate between t-PA and u-PA. Mutagenesis of the P3 and P4 residues of
      plasminogen activator inhibitor type 1, the primary physiological inhibitor of
      both t-PA and u-PA, confirmed this prediction and indicated a predominant role
      for the P3 residue. Appropriate replacement of both the P3 and P4 residues
      enhanced the t-PA specificity of plasminogen activator inhibitor type 1 by a
      factor of 600, and mutation of the P3 residue alone increased this selectivity by
      a factor of 170. These results demonstrate that the combination of substrate
      phage display and substrate subtraction methods can be used to discover
      specificity differences between very closely related enzymes and that this
      information can be utilized to create highly selective inhibitors.

PMID- 9195974
TI  - Analysis of a yeast SNARE complex reveals remarkable similarity to the neuronal
      SNARE complex and a novel function for the C terminus of the SNAP-25 homolog,
      Sec9.
AB  - SNARE proteins represent a family of related proteins that are thought to have a
      central role in vesicle targeting and fusion in all eukaryotic cells. The binding
      properties of the neuronal proteins synaptobrevin 1 (VAMP1), syntaxin 1, SNAP-25,
      and soluble N-ethylmaleimide-sensitive factor attachment protein (alpha-SNAP),
      have been extensively studied. We report here the first biochemical
      characterization of a nonneuronal SNARE complex using recombinant forms of the
      yeast exocytic SNARE proteins Snc1, Sso1, and Sec9 and the yeast alpha-SNAP
      homolog, Sec17. Despite the low level of sequence identity, the association
      properties of the yeast and neuronal complexes are remarkably similar. The most
      striking difference we have found between the yeast and neuronal proteins is that
      individually neither of the target membrane SNAREs (t-SNAREs), Sso1 nor Sec9,
      show any detectable binding to the synaptobrevin homolog, Snc1. However, as a
      hetero-oligomeric complex, Sec9 and Sso1 show strong binding to Snc1. The clear
      dependence on the Sso1-Sec9 complex for t-SNARE function suggests that regulating
      the formation of this complex may be a key step in determining the site of
      vesicle fusion. In addition, we have used this in vitro assay to examine the
      biochemical effects of several mutations in Sec9 that result in pronounced growth
      defects in vivo. As expected, a temperature-sensitive mutation in the region most
      highly conserved between Sec9 and SNAP-25 is severely diminished in its ability
      to bind Sso1 and Snc1 in vitro. In contrast, a temperature-sensitive mutation
      near the C terminus of Sec9 shows no defect in SNARE binding in vitro. Similarly,
      a deletion of the C-terminal 17 residues, which is lethal in vivo, also binds
      Sso1 and Snc1 normally in vitro. Interestingly, we find that these same two C
      terminal mutants, but not mutants that show SNARE assembly defects in vitro, act
      as potent dominant negative alleles when expressed behind a strong regulated
      promoter. Taken together these results suggest that the C-terminal domain of Sec9
      is specifically required for a novel interaction that is required at a step
      following SNARE assembly.

PMID- 9195975
TI  - Reconstitution in vitro of the V1 complex from the yeast vacuolar proton
      translocating ATPase. Assembly recapitulates mechanism.
AB  - Oligomeric assembly is a fundamental aspect of many complex enzymes. Using our
      native gel technique for examining subcomplexes of the V-ATPase V1 sector, we
      have developed an in vitro reconstitution assay for assembly of this complex.
      Assembly of complex II, the soluble V1 complex observed in native gels, is
      dependent upon the presence of divalent cations and physiological temperatures.
      Assembly of soluble V1 can occur in a stepwise fashion from smaller subcomplexes
      found in some strains deleted for V-ATPase subunits. Specifically, V1 can be
      assembled directly from complex III (subunits E and G) with complex IV (subunits
      A, B, D, and F) without prior disassembly of complex IV. The formation of complex
      III in vivo is also shown to be essential and could not be achieved in vitro.
      Assembly from simpler precursors is possible and is enhanced by added ATP.
      Assembly can be blocked by N-ethylmaleimide in a Vma1p (subunit A)-specific
      manner. From these data, we extend our previous model to consider an assembly
      pathway whose steps reflect the catalytic mechanism of the Boyer binding-change
      model.

PMID- 9195976
TI  - Argininosuccinate synthetase overexpression in vascular smooth muscle cells
      potentiates immunostimulant-induced NO production.
AB  - Immunostimulants trigger vascular smooth muscle cells (VSMC) to express both the
      inducible isoform of NO synthase (iNOS) and argininosuccinate synthetase (AS).
      With constitutively expressed argininosuccinate lyase (AL), AS confers cells with
      an Arg/Cit cycle that can sustain NO production via continuous regeneration of
      the NOS substrate, L-arginine (Arg), from the NOS coproduct, L-citrulline (Cit).
      To assess whether NO synthesis can be rate-limited by Arg recycling, we tested
      whether AS-overexpressing cells have an enhanced capacity for immununostimulant
      induced NO synthesis. Rat VSMC were stably transfected with human AS cDNA in a
      eukaryotic cell expression vector, driven by a strong viral promoter. AS activity
      in transfected VSMC exceeded that induced in untransfected cells treated for 24 h
      with a combination of bacterial lipopolysaccharide and interferon-gamma
      (LPS/IFN). AS activity was predominantly associated with membranes but was also
      found in cytosol. Recombinant AS was purified from cytosol and possessed a
      specific activity exceeding that reported for native AS. Western blotting
      verified the basal expression of AS antigen in membranes from untreated AS
      transfected VSMC and from untransfected VSMC after 24 h exposure to LPS/IFN.
      Epifluorescence histochemistry revealed a punctate distribution of AS antigen in
      transfected cells, consistent with a predominant membrane localization.
      Remarkably, on a per cell basis, LPS/IFN-induced NO production was 3-4-fold
      greater in AS-transfected cells than untransfected VSMC. In untransfected VSMC,
      maximal NO production during 48 h required millimolar Arg; notably, Cit was
      needed at approximately 3-fold higher concentrations than Arg for a comparable NO
      synthesis rate. In contrast, AS-transfected VSMC utilized Arg and Cit equi
      effectively and at much lower concentrations; 100 microM of either precursor
      supported a maximal rate of NO synthesis for 48 h. The enhanced ability of AS
      transfected cells to produce NO, compared with untransfected cells, could not be
      ascribed to differences in iNOS protein content or LPS/IFN potency for
      immunoactivation. We conclude that transfection with AS provides a continuous
      flux of Arg which drives NO synthesis in immunoactivated VSMC. Arg regeneration
      by AS is rate-limiting to NO synthesis and apparently provides iNOS with a
      preferred cellular source of Arg. In accord with the reported "channeling" of
      substrates by urea cycle enzymes, we hypothesize that the Arg/Cit cycle
      sequesters a discrete pool of recyclable substrate that sustains high-output NO
      synthesis.

PMID- 9195977
TI  - Box 3-independent signaling mechanisms are involved in leukemia inhibitory factor
      receptor alpha- and gp130-mediated stimulation of mitogen-activated protein
      kinase. Evidence for participation of multiple signaling pathways which converge
      at Ras.
AB  - Chimeric receptors containing the entire or various cytoplasmic domains of either
      gp130 or leukemia inhibitory factor receptor alpha (LIFR) were used to identify
      signaling molecules and regions of these polypeptides required for the
      stimulation of mitogen-activated protein kinase (MAPK). Coexpression of dominant
      negative Jak2 inhibited chimeric receptor-stimulated MAPK activity by
      approximately 70%, while expression of dominant-negative Ras completely blocked
      MAPK activation by either receptor polypeptide. Deletion analysis identified a 24
      amino acid region of gp130 that was necessary for maximal stimulation of MAPK,
      and contained box 3 (positions 120-129) and a consensus tyrosine binding motif
      (Tyr-118) for the protein-tyrosine phosphatase, SHP2. Expression of receptors
      lacking this region or of chimeric gp130(Y118F) point mutants inhibited MAPK
      activity by approximately 55%, suggesting that Tyr-118, but not box 3, was
      required during activation of MAPK by gp130. Similarly, expression of chimeric
      LIFR constructs lacking box 3 maximally stimulated MAPK activity, while those
      lacking Tyr-115, a putative SHP2 binding site, inhibited stimulation of MAPK by
      this polypeptide. Our results demonstrate that gp130 and LIFR stimulate MAPK
      activity through box 3-independent mechanisms involving: (i) effects at Tyr-118
      and Tyr-115, respectively, for maximal stimulation of MAPK activity and (ii) a
      Jak/Tyk-dependent pathway that, together with Tyr-118- or Tyr-115-generated
      signals, converges at the level of Ras during activation of MAPK by cytokine.

PMID- 9195978
TI  - Novel progesterone target genes identified by an improved differential display
      technique suggest that progestin-induced growth inhibition of breast cancer cells
      coincides with enhancement of differentiation.
AB  - Progesterone is an important regulator of normal and malignant breast epithelial
      cells. In addition to stimulating development of normal mammary epithelium, it
      can be used to treat hormone-dependent breast tumors. However, the mechanism of
      growth inhibition by progestins is poorly understood, and only a limited number
      of progesterone target genes are known so far. We therefore decided to clone such
      target genes by means of differential display polymerase chain reaction. In this
      paper, we describe an improved differential display strategy that eliminates
      false positives, along with the identification of nine positive (TSC-22, CD-9,
      Na+/K+-ATPase alpha1, desmoplakin, CD-59, FKBP51, and three unknown genes) and
      one negative progesterone target genes (annexin-VI) from the mammary carcinoma
      cell line T47D, which is growth-inhibited by progestins. None of these genes have
      been reported before to be progesterone targets. Regulation of desmoplakin, CD-9,
      CD-59, Na+/K+-ATPase alpha1, and annexin-VI by the progestin suggests that
      progesterone induces T47D cells to differentiate. Three of these genes were
      repressed by estradiol and up-regulated by the progestin. Estradiol treatment of
      T47D cells also leads to formation of lamellipodia and delocalization of two cell
      adhesion proteins, E-cadherin and alpha-catenin. All these effects were reversed
      by the progestin. These data suggest that estradiol dedifferentiates T47D cells,
      while progestins have the opposite effect. This may be linked to the capacity of
      progestins to inhibit tumor growth.

PMID- 9195979
TI  - Mice deficient in cellular glutathione peroxidase develop normally and show no
      increased sensitivity to hyperoxia.
AB  - Glutathione peroxidase, a selenium-containing enzyme, is believed to protect
      cells from the toxicity of hydroperoxides. The physiological role of this enzyme
      has previously been implicated mainly using animals fed with a selenium-deficient
      diet. Although selenium deficiency also affects the activity of several other
      cellular selenium-containing enzymes, a dramatic decrease of glutathione
      peroxidase activity has been postulated to play a role in the pathogenesis of a
      number of diseases, particularly those whose progression is associated with an
      overproduction of reactive oxygen species, found in selenium-deficient animals.
      To further clarify the physiological relevance of this enzyme, a model of mice
      deficient in cellular glutathione peroxidase (GSHPx-1), the major isoform of
      glutathione peroxidase ubiquitously expressed in all types of cells, was
      generated by gene-targeting technology. Mice deficient in this enzyme were
      apparently healthy and fertile and showed no increased sensitivity to hyperoxia.
      Their tissues exhibited neither a retarded rate in consuming extracellular
      hydrogen peroxide nor an increased content of protein carbonyl groups and lipid
      peroxidation compared with those of wild-type mice. However, platelets from GSHPx
      1-deficient mice incubated with arachidonic acid generated less 12
      hydroxyeicosatetraenoic acid and more polar products relative to control
      platelets at a higher concentration of arachidonic acid, presumably reflecting a
      decreased ability to reduce the 12-hydroperoxyeicosatetraenoic acid intermediate.
      These results suggest that the contribution of GSHPx-1 to the cellular
      antioxidant mechanism under normal animal development and physiological
      conditions and to the pulmonary defense against hyperoxic insult is very limited.
      Nevertheless, the potential antioxidant role of this enzyme in protecting cells
      and animals against the pathogenic effect of reactive oxygen species in other
      disorders remains to be defined. The knockout mouse model described in this
      report will also provide a new tool for future study to distinguish the
      physiological role of this enzyme from other selenium-containing proteins in
      mammals under normal and disease states.

PMID- 9195980
TI  - Cross-linking of the delta subunit to one of the three alpha subunits has no
      effect on functioning, as expected if delta is a part of the stator that links
      the F1 and F0 parts of the Escherichia coli ATP synthase.
AB  - A mutant of the Escherichia coli F1F0-ATPase has been generated (alphaQ2C) in
      which the glutamine at position 2 of the alpha subunit has been replaced with a
      cysteine residue. Cu2+ treatment of ECF1 from this mutant cross-linked an alpha
      subunit to the delta subunit in high yield. Two different sites of disulfide bond
      formation were involved, i.e. between Cys90 (or the closely spaced Cys47) of
      alpha with Cys140 of delta, and between Cys2 of alpha and Cys140 of delta. Small
      amounts of other cross-linked products, including alpha-alpha, delta internal,
      and alpha-alpha-delta were obtained. In ECF1F0, there was no cross-linking
      between the intrinsic Cys of alpha and Cys140. Instead, the product generated
      between Cys2 of alpha and Cys140 of delta was obtained at near 90% yield. Small
      amounts of alpha-alpha and delta internal were present, and under high Cu2+
      concentrations, alpha-alpha-delta was also formed. The ATPase activity of ECF1
      and ECF1F0 was not significantly affected by the presence of these cross-links.
      When Cys140 of delta was first modified with N-ethylmaleimide in ECF1F0, an alpha
      delta cross-link was still produced, although in lower yield, between Cys64 of
      delta and Cys2 of alpha. ATP hydrolysis-linked proton pumping of inner membranes
      from the mutant alpha2QC was only marginally affected by cross-linking of the
      alpha to the delta subunit. These results indicate that Cys140 and Cys64 of the
      delta subunit and Cys2 of the alpha subunit are in close proximity. This places
      the delta subunit near the top of the alpha-beta hexagon and not in the stalk
      region. As fixing the delta to the alpha by cross-linking does not greatly impair
      either the ATPase function of the enzyme, or coupled proton translocation, we
      argue that the delta subunit forms a portion of the stator linking F1 to F0.

PMID- 9195981
TI  - A novel mechanism of JNK1 activation. Nuclear translocation and activation of
      JNK1 during ischemia and reperfusion.
AB  - Cytokines and various cellular stresses are known to activate c-Jun NH2-terminal
      kinase (JNK), which plays a role in conveying signals from the cytosol to the
      nucleus. Here we investigate the translocation and activation of JNK1 during
      ischemia and reperfusion in perfused rat heart. Ischemia induces the
      translocation of JNK1 from the cytosol fraction to the nuclear fraction in a time
      dependent manner. Immunohistochemical observation also shows that JNK1 staining
      in the nucleus is enhanced after ischemia. During reperfusion after ischemia,
      further nuclear translocation of JNK1 is apparently inhibited. In contrast, JNK1
      activity in the nuclear fraction does not increased during ischemia but increases
      significantly during reperfusion with a peak at 10 min of reperfusion. The
      activation of JNK1 is confirmed by the phosphorylation of endogenous c-Jun (Ser
      73) with similar kinetics. The level of c-jun mRNA also increases during
      reperfusion but not during ischemia. Based on fractionation and
      immunohistochemical analyses, an upstream kinase for JNK1, SAPK/ERK kinase 1
      (SEK1), is constantly present in both the nucleus and cytoplasm throughout
      ischemia and reperfusion, whereas an upstream kinase for mitogen-activated
      protein kinase, MAPK/ERK kinase 1, remains in the cytosol. Furthermore,
      phosphorylation at Thr-223 of SEK1, necessary for its activation, rapidly
      increases in the nuclear fraction during postischemic reperfusion. These findings
      demonstrate that JNK1 translocates to the nucleus during ischemia without
      activation and is then activated during reperfusion, probably by SEK1 in the
      nucleus.

PMID- 9195982
TI  - Molecular cloning and sequencing of a novel invertebrate intestinal mucin cDNA.
AB  - The first invertebrate intestinal mucin, termed insect intestinal mucin (IIM),
      was recently identified from Trichoplusia ni larvae (Wang, P., and Granados, R.
      R. (1997) Proc. Natl. Acad. Sci. U. S. A. , in press). We report the cDNA cloning
      and sequencing of IIM, which is only the second completely sequenced intestinal
      mucin after human intestinal mucin, MUC2. To clone and sequence the cDNA for IIM,
      a T. ni larval midgut cDNA expression library was constructed and screened with
      an anti-IIM antiserum. Two full-length cDNA clones for IIM were identified and
      sequenced. The deduced proteins from the two cDNA clones contained 807 and 788
      amino acid residues, respectively. The structural organization of IIM is similar
      to that of MUC2, containing a 25-amino acid signal leading sequence and two
      threonine/proline/alanine-rich tandem repeat domains flanked by cysteine-rich
      sequences. One tandem repeat domain contained two repeating units, TTTQAP and
      AATTP, and the other contained one repeating unit, TAAP. The cysteine-rich
      regions showed potential chitin binding features. By immunolocalization in tissue
      sections, it was determined that IIM is expressed in midgut tissues. The IIM mRNA
      is abundant in the midgut tissue, and Northern blot analysis indicated that IIM
      transcripts were not polydispersed as is found in mammalian mucin transcription.

PMID- 9195983
TI  - Shrinkage-induced protein tyrosine phosphorylation in Chinese hamster ovary
      cells.
AB  - To investigate the signal transduction of osmotic stress, we examined
      hypertonicity-induced tyrosine phosphorylations in Chinese hamster ovary cells.
      Hyperosmosis elicited characteristic phosphotyrosine accumulation in at least 3
      proteins (approximately 42, approximately 85, and approximately 120 kDa). The
      most prominent response occurred in the 85-kDa band (p85) whose phosphorylation
      was rapid, sustained, apparent already at mild hypertonicity (350 mosM),
      proportional to the extracellular osmotic concentration, and reversible.
      Hyperosmotic environment could not induce tyrosine phosphorylation if cell
      shrinkage was prevented by nystatin and appropriately composed media. Conversely,
      isotonic shrinkage caused strong tyrosine phosphorylation. Thus, the initial
      signal is a decrease in cell volume and not an increase in the intra- or
      extracellular osmotic concentration, or a rise in cytosolic K+ and Cl- levels.
      Tyrosine phosphorylation of p85 was not due to the hypertonicity-induced protein
      kinase C-dependent stimulation of the extracellular signal-regulated protein
      kinase, nor to the activation of stress-activated protein kinases. Tonicity
      responsive proteins interacted with Grb2-glutathione S-transferase fusion
      proteins: the 120-kDa protein complexed with the SH2 and both SH3 domains,
      whereas p85 associated with the SH2 and the N-terminal SH3 domains of the
      adapter. Tyrosine phosphorylation of p85 is a sensitive indicator of reduced
      intracellular hydration and might signify a hitherto unrecognized, early volume
      dependent signaling event.

PMID- 9195984
TI  - Mechanisms of suppression of inducible nitric-oxide synthase (iNOS) expression in
      interferon (IFN)-gamma-stimulated RAW 264.7 cells by dexamethasone. Evidence for
      glucocorticoid-induced degradation of iNOS protein by calpain as a key step in
      post-transcriptional regulation.
AB  - The murine macrophage cell line RAW 264.7 expresses inducible nitric-oxide
      synthase (iNOS) activity upon stimulation with interferon (IFN)-gamma and/or
      bacterial lipopolysaccharide. We have studied the mechanisms by which the
      synthetic glucocorticoid dexamethasone suppresses IFN-gamma-stimulated iNOS
      expression in RAW 264.7 cells. Treatment of cells with dexamethasone reduces the
      formation of nitrite, one of the stable end products of NO production measured in
      culture supernatants with an IC50 of 9 nM. The reduction of iNOS activity is
      caused by decreased iNOS protein levels as assessed by immunoblotting using a
      specific anti-iNOS antibody. Dexamethasone treatment also reduces the formation
      of iNOS mRNA steady state levels to about 50% in IFN-gamma-stimulated cells. This
      is due to decreased iNOS gene transcription and iNOS mRNA stability. More
      importantly, dexamethasone reduces the amount of iNOS protein by two additional
      mechanisms: reduction of the translation of iNOS mRNA and increased degradation
      of the iNOS protein. Using a specific protease inhibitor for the cysteine
      protease calpain I, N-acetyl-Leu-Leu-norleucinal (calpain inhibitor I), the
      enhanced proteolysis of the iNOS protein can efficiently be blocked, whereas
      other protease inhibitors such as tosyl-L-lysine chloromethyl ketone have no
      effect. Dexamethasone does not significantly alter calpain gene expression.
      Northern blot analyses reveal that calpain mRNA steady state levels are virtually
      not affected upon incubation of the cells with IFN-gamma and dexamethasone.
      Immunoprecipitation using a polyclonal anti-calpain antibody reveals that calpain
      protein levels are also not affected by the glucocorticoid. This is the first
      evidence that the iNOS protein is a molecular target for the cysteine protease
      calpain.

PMID- 9195985
TI  - A CACCC box-like cis-regulatory element of the Epstein-Barr virus ED-L2 promoter
      interacts with a novel transcriptional factor in tissue-specific squamous
      epithelia.
AB  - The Epstein-Barr (EBV) virus induces a lytic state after infecting epithelial
      cells. Subsequently, there is infection of B lymphocytes with two types of
      cycles, latent and lytic. Apart from linkage of the EBV latent membrane protein-1
      (LMP-1) with benign and malignant conditions of squamous epithelial cells, little
      is known about other EBV gene products that may be important in these processes
      as well as cellular transcriptional factors that regulate EBV gene expression in
      these epithelial cells. The EBV ED-L2 promoter, an early lytic cycle promoter, is
      located upstream of a transcription start site for a short open reading frame
      designated BNLF2 and just downstream of the BNLF1 (LMP-1) open reading frame. We
      have previously used the EBV ED-L2 promoter to target oncogenes in transgenic
      mice, resulting in tissue-specific expression in the tongue, esophagus,
      forestomach, and skin, all sharing stratifying squamous epithelia, alternatively
      called keratinocytes. In the present study, we have functionally dissected the ED
      L2 promoter by making deletion constructs fused to the luciferase reporter gene
      with transient transfections into squamous and nonsquamous epithelial cell lines
      as well as B lymphocytes. A CACCC box-like cis-regulatory element has been
      identified that is located between -218 and -187 base pairs of the ED-L2 promoter
      that confers significant promoter activity only in squamous epithelial cells.
      This cis-regulatory element is active in a heterologous minimal herpes simplex
      virus thymidine kinase promoter reporter gene construct when transfected into
      squamous epithelial cells but not in nonsquamous epithelial cells. DNA gel
      mobility shift assays have led to the identification of DNA-protein complexes
      that bind the CACCC box-like element. One of these proteins is a novel
      transcriptional factor that is uniquely active in stratified squamous epithelial
      cells, designated as keratinocyte specific factor (KSF). KSF may be related to
      Sp1 but appears to be distinct from Sp1. In addition, KSF may interact with
      related or identical cis-regulatory elements found in human papillomavirus-11 E6
      and cytokeratin K3 promoters that are active in keratinocytes. In aggregate, KSF
      may be important in the transcriptional regulation of viral and eukaryotic genes
      in keratinocytes.

PMID- 9195986
TI  - Identification and characterization of a nerve terminal-enriched amphiphysin
      isoform.
AB  - Amphiphysin is a nerve terminal-enriched protein thought to function in synaptic
      vesicle endocytosis, in part through Src homology 3 (SH3) domain-mediated
      interactions with dynamin and synaptojanin. Here, we report the characterization
      of a novel amphiphysin isoform (termed amphiphysin II) that was identified
      through a homology search of the data base of expressed sequence tags. Antibodies
      specific to amphiphysin II recognize a 90-kDa protein on Western blot that is
      brain-specific and highly enriched in nerve terminals. Like amphiphysin (now
      referred to as amphiphysin I), amphiphysin II binds to dynamin and synaptojanin
      through its SH3 domain. Further, both proteins bind directly to clathrin in an
      SH3 domain-independent manner. Taken together, these data suggest that
      amphiphysin II may participate with amphiphysin I in the regulation of synaptic
      vesicle endocytosis.

PMID- 9195987
TI  - Meeting report: 10th International Mouse Genome Conference.

PMID- 9195988
TI  - The origins of mouse genetics: beyond the Bussey Institution. I. Cold Spring
      Harbor: the station for experimental evolution and the 'Mouse Club of America'.

PMID- 9195989
TI  - HOSEpipe--a WWW-hosted data management and analysis system for STS content
      mapping projects.
AB  - We have developed a data management system, 'HOSEpipe' (High Output STS
      Evaluation pipeline) to aid sample tracking and data analysis in STS content
      mapping projects. The system is based around a World Wide Web (WWW) server that
      provides a number of pages including forms for sample processing and data entry
      accessible via a standard WWW browser application. The system is split into two
      main modules: firstly, a sequence evaluation and annotation module that takes de
      novo sequence for a potential STS, screens it against existing STSs and DNA
      sequence databases, followed by appropriate primer sequence design; secondly, a
      module that handles YAC library STS screening and includes facilities for both
      sample tracking and experimental data analysis. We present the design and
      rationale of the HOSEpipe system and its development to support a whole
      chromosomal physical mapping project. This software and design approach is
      potentially applicable to physical mapping projects of varying sizes and
      resolution and to similar projects, such as sample sequencing and the
      construction of sequence-ready maps.

PMID- 9195990
TI  - A candidate model for Angelman syndrome in the mouse.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are well-recognized
      examples of imprinting in humans. They occur most commonly with paternal and
      maternal 15q11-13 deletions, but also with maternal and paternal disomy. Both
      syndromes have also occurred more rarely in association with smaller deletions
      seemingly causing abnormal imprinting. A putative mouse model of PWS, occurring
      with maternal duplication (partial maternal disomy) for the homologous region,
      has been described in a previous paper but, although a second imprinting effect
      that could have provided a mouse model of AS was found, it appeared to be
      associated with a slightly different region of the chromosome. Here, we provide
      evidence that the same region is in fact involved and further demonstrate that
      animals with paternal duplication for the region exhibit characteristics of AS
      patients. A mouse model of AS is, therefore, strongly indicated.

PMID- 9195992
TI  - Isolation of coding sequences from bovine cosmids by means of exon trapping.
AB  - Exon trapping was employed to identify coding sequences from a collection of 46
      bovine cosmids, previously characterized for the presence of microsatellite
      markers and physically mapped to chromosomes by FISH. The sequence analysis of
      104 clones revealed 18 putative exons, 10 of which showed near identity to known
      sequences. Among these were the human (cytosine-5)-methyltransferase (DNMT), ATP
      citrate lyase (ACLY), the mouse Lbcl1 oncogene, the bovine mitochondrial
      aconitase (ACO2) and beta-arrestin 1 (ARR1). The chromosomal localization of the
      cloned exons was inferred from the localization of the parent cosmids. DNMT and
      ACLY were not previously known in cattle, but the physical localization of the
      cloned bovine exons is in agreement with the published comparative human and
      bovine maps. The trapping of exons for bovine ACO2 and ARR1 confirms the
      available mapping information based on synteny and provides a physical assignment
      for the genes.

PMID- 9195991
TI  - Eyes absent: a gene family found in several metazoan phyla.
AB  - Genes related to the Drosophila eyes absent gene were identified in vertebrates
      (mouse and human), mollusks (squid), and nematodes (C. elegans). Proteins encoded
      by these genes consist of conserved C-terminal and variable N-terminal domains.
      In the conserved 271-amino acid C-terminal region, Drosophila and vertebrate
      proteins are 65-67% identical. A vertebrate homolog of eyes absent, designated
      Eya2, was mapped to Chromosome (Chr) 2 in the mouse and to Chr 20q13.1 in human.
      Eya2 shows a dynamic pattern of expression during development. In the mouse,
      expression of Eya2 was first detected in 8.5-day embryos in the region of head
      ectoderm fated to become the forebrain. At later stages of development, Eya2 is
      expressed in the olfactory placode and in a variety of neural crest derivatives.
      In the eye, expression of Eya2 was first detected after formation of the lens
      vesicle. At day 17.5, the highest level of Eya2 mRNA was observed in primary lens
      fibers. Low levels of Eya2 expression was detected in retina, sclera, and cornea.
      By postnatal day 10, Eya2 was expressed in secondary lens fibers, cornea, and
      retina. Although Eya2 is expressed relatively late in eye development, it belongs
      to the growing list of factors that may be essential for eye development across
      metazoan phyla. Like members of the Pax-6 gene family, eyes absent gene family
      members were probably first involved in functions not related to vision, with
      recruitment for visual system formation and function occurring later.

PMID- 9195993
TI  - Organization and expression of bovine TSPY.
AB  - We have isolated genomic sequences as well as transcripts from the bovine homolog
      of the human testis-specific protein, Y-encoded, TSPY which-in both species-is
      located on the Y Chromosome (Chr), organized as a gene family with a variable
      number of members, and expressed exclusively in the testis. 1266 bp of bovine
      TSPY specific sequence have been isolated from a testis cDNA library, by RT-PCR
      analyses and by Rapid Amplification of cDNA Ends (RACE). A bovine TSPY gene 4 is
      organized in seven exons, and transcripts are polyadenylated at various 3' ends.
      Consensus polyadenylation signals AAUUAAA are missing. Microheterogeneous
      sequence variation is found between TSPY family members. In addition, homologies
      to other Y-located repeated sequence families, BRY, have been discovered; these
      sequences are presumably derived from ancient members of the TSPY cluster, now
      forming a separate, probably nonfunctional subfamily. Bovine TSPY is subject to
      differential splicing. In the adult, it is expressed in early germ-cell stages,
      and expression could also be detected in fetal testis. Comparison with the human
      homolog shows the highest degree of similarity in the coding regions of exons 2,
      3, and 4, which are also precisely conserved regarding their length.

PMID- 9195994
TI  - High-resolution mapping by YAC fragmentation of a 2.5-Mb Xp22 region containing
      the human RS, KFSD and CLS disease genes.
AB  - The disease loci for X-linked Retinoschisis (RS), Keratosis follicularis
      spinulosa decalvans (KFSD), and Coffin-Lowry syndrome (CLS) have been localized
      to the same, small region in Xp22 on the human X Chromosome (Chr). To generate a
      high-resolution map of the available contig in this area, we have used the YAC
      fragmentation vectors pBP108/ADE2 and pBP109/ADE2 and generated fragmented YACs
      from a 2.5-Mb YAC (y939H7) spanning the mentioned disease gene candidate regions.
      Forty-seven fragmented YACs were generated and analyzed, ranging in size from 170
      kb to over 2400 kb. The resulting YAC fragmentation panel was used to construct a
      detailed restriction map of the region and has been used to bin clones and
      markers. As a deletion panel, it will present a valuable resource for further
      mapping.

PMID- 9195995
TI  - Mapping of the mouse Tdgf1 gene and Tdgf pseudogenes.
AB  - Teratocarcinoma-derived growth factor-1 (Tdgf1), a member of the "EGF family" of
      growth factors, is expressed during mouse gastrulation in the forming mesoderm
      and later in the truncus arteriosus of the developing heart. In humans, TDGF1 is
      highly expressed in germ cell tumors and in colon and mammary carcinomas. In
      mouse, one gene (Tdgf1) and two pseudogenes (Tdgf1-ps1 and Tdgf1-ps2) have been
      isolated and characterized. Tdgf1 corresponds to the gene expressed in F9
      teratocarcinoma cells. Tdgf1-ps1 and Tdgf1-ps2 are two intronless sequences with
      all the characteristics of retroposons. In the present paper, we assign the
      chromosomal location for Tdgf1, Tdgf1-ps1, and Tdgf1-ps2 sequences to Chromosomes
      (Chrs) 9, 16, and 17, respectively. Two previously described mouse mutants, scant
      hair (sch) and fur deficient (fd), map near the Tdgf1 gene. Analysis of their DNA
      coding region provided no evidence that Tdgf1 could be the responsible gene for
      these phenotypes. Finally, analysis of the DNA from several Mus musculus strains
      and from Mus spretus mice revealed a highly variable restriction pattern and the
      absence of the Tdgf1-ps1 genomic sequence from the Mus spretus genome.

PMID- 9195996
TI  - Microsatellite DNA variants between the FVB/N and C3HeB/FeJLe and C57BL/6J mouse
      strains.

PMID- 9195997
TI  - An expanded collection of mouse Y chromosome RDA clones.

PMID- 9195998
TI  - The mouse homologs of RELA and MLK3 are located within a 120-kb fragment on
      chromosome 19.

PMID- 9196000
TI  - Localization of the casein kinase II beta-subunit gene within the mouse H-2
      complex class III region and comparison of expression with Bat genes.

PMID- 9195999
TI  - Molecular characterization of the mouse very-long-chain acyl-CoA dehydrogenase
      gene.

PMID- 9196002
TI  - Identification and mapping of a novel human gene, HRMT1L1, homologous to the rat
      protein arginine N-methyltransferase 1 (PRMT1) gene.

PMID- 9196001
TI  - Cloning of the bovine and rat Fanconi anemia group C cDNA.

PMID- 9196003
TI  - Comparative mapping in cattle of genes located on human chromosome 18.

PMID- 9196004
TI  - Mapping of eight human chromosome 1 orthologs to cattle chromosomes 3 and 16.

PMID- 9196005
TI  - Otp maps to mouse chromosome 13.

PMID- 9196006
TI  - Mapping of Ppp5c, the gene encoding protein phosphatase 5, to mouse chromosome 7.

PMID- 9196007
TI  - Localization of profilin-1 (Pfn1) and a related sequence (Pfn1-rs) to mouse
      chromosomes 11 and 15 respectively.

PMID- 9196008
TI  - Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse
      chromosome 5.

PMID- 9196009
TI  - Genetic mapping in the mouse of Kif4, a gene encoding a kinesin-like motor
      protein.

PMID- 9196010
TI  - Managing risk in gynecologic cytology: reactive and unsatisfactory smears.

PMID- 9196011
TI  - Clinicopathologic correlation of the unsatisfactory Papanicolaou smear.
AB  - BACKGROUND: The 1991 Bethesda System for cervical/vaginal cytology reporting
      defined adequacy criteria for the unsatisfactory designation. Most laboratories
      have implemented these criteria, but clinical implications have not been
      established. METHODS: Researchers at two university hospitals retrieved by
      computer search all unsatisfactory Papanicolaou (Pap) smears taken between
      January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were
      unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate
      of 6.5%). Time interval to follow-up and clinicopathologic outcome were
      determined. RESULTS: Approximately 26% of unsatisfactory Pap smears were from
      patients with a history of epithelial abnormalities. The majority (129 of 208
      specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months,
      5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no
      follow-up. The first repeat Pap smear or histologic specimen in 144 patients with
      follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous
      cells of undetermined significance in 15 (10%), squamous intraepithelial lesion
      (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing
      to the unsatisfactory smears on histologic specimens (12%) included cervicitis,
      endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities
      after the first repeat specimen were noted in 7 patients (5%). A total of 23 of
      144 initial unsatisfactory specimens (16% )were found to be from patients
      diagnosed with SIL or malignancy when all follow-up specimens were analyzed.
      CONCLUSIONS: The majority of patients with unsatisfactory Pap smears had follow
      up studies within 6 months. A significant number (16%) of those with follow-up
      had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also
      contributed to unsatisfactory smears. This patient subset was more likely to have
      a history of abnormalities, confirming the importance of peer/hierarchical review
      of unsatisfactory smears.

PMID- 9196013
TI  - Fine-needle aspiration biopsy in the diagnosis and management of bone lesions: a
      study of 450 cases.
AB  - BACKGROUND: Fine-needle aspiration (FNA) biopsy has proved to be a cost-effective
      technique, with low complication risks and high diagnostic value in
      distinguishing neoplastic versus nonneoplastic lesions in many organs. This study
      was designed to determine the reliability, areas of diagnostic difficulty, and
      limitations of FNA in the diagnosis of bone lesions encountered in a university
      affiliated tertiary care hospital. METHODS: The cytology of 450 FNA biopsies of
      bone lesions, performed on 427 patients between 1979 and 1996, were reviewed. The
      results were correlated with the corresponding histology when available, and with
      clinical follow-up, in an attempt to define the role of FNA in managing patients
      with bony lesions. RESULTS: The patients ranged in age from 5 to 94 years, with a
      male-to-female ratio of 1.25:1. The spine was the most frequently aspirated site
      (49%), followed by the ilium, sacrum, mandible, ribs, and femur. Three hundred
      and eighty-five aspirates (86%) were adequate for evaluation, with 215 cases
      diagnosed cytologically as positive for malignancy, 11 cases as suspicious but
      not diagnostic of malignancy, and 2 cases as inconclusive. One hundred and fifty
      seven cases were interpreted as showing no evidence of malignancy. Metastatic
      carcinoma was present in 175 of the 215 malignant aspirates, and 67% of these
      were adenocarcinomas. Forty cases were primary malignant bone neoplasms,
      including myeloma, lymphoma, Ewing's sarcoma, chondrosarcoma, ameloblastoma,
      chordoma, neurofibrosarcoma, and unclassified high grade sarcoma. False-negative
      diagnoses were rendered in ten cases; however, on review, material representative
      of the bone lesion was not present in six cases. Five cases were correctly
      diagnosed as malignant but were misclassified with regard to the type of
      malignancy. CONCLUSIONS: FNA biopsy of bone lesions is a reliable and easily
      performed diagnostic test for metastatic and primary bone tumors. False-positive
      results have major therapeutic implications, hence the significance of the
      authors' conservative diagnostic approach, which resulted in a false-positive
      rate of 0.2%. Areas of difficulty were due to inadequate sampling or
      misclassification with regard to the exact type of malignancy. The simplicity and
      accuracy of this procedure, which does not require any surgical incisions (open
      biopsy or manipulation), supports its important role in triaging and managing
      bone lesions with minimum risk or morbidity.

PMID- 9196012
TI  - Reactive cellular change: is there an increased risk for squamous intraepithelial
      lesions?
AB  - BACKGROUND: The aim of this study was to evaluate the rate of squamous
      intraepithelial lesions (SIL) in women with reactive cellular change (RCC)
      cervical smears and compare the results with a control group with within normal
      limit (WNL) smears. METHODS: The study group was comprised of 1000 women with RCC
      and a control group of 1000 women with WNL cervical smears diagnosed over an 8
      month period. Results of the first follow-up (FU) smears were evaluated and
      compared between the two groups. FU smears with a diagnosis of SIL were reviewed
      along with the original RCC or WNL smears. RESULTS: Six hundred and thirteen
      women from the RCC group and 640 from the WNL group had FU smears. The mean time
      to FU was 11.0 and 13.8 months, respectively. FU revealed SIL in 24 of 613 smears
      in the RCC group (20 low grade [L] SIL and 4 high grade [H] SIL), (3.9%) and in
      10 of 640 smears in the WNL group (10 LSIL and 0 HSIL) (1.6%). Fisher's exact
      test (two-tailed) showed statistical significance (P = 0.014). On retrospective
      review of the FU smears diagnosed as SIL and their corresponding original RCC or
      WNL smears, four RCC smears were upgraded to atypical squamous cells of
      undetermined significance (ASCUS). The remaining diagnoses remained unchanged.
      CONCLUSIONS: Women with RCC are more likely to have SIL on a FU smear compared
      with women with WNL smears (3.9% vs. 1.6%). It is important to emphasize that in
      the authors' laboratory, the rate of SIL in women with ASCUS is much higher
      (24%). Awareness of these rates combined with the clinical history may help
      clinicians determine whether women with RCC require closer FU.

PMID- 9196014
TI  - CD44 immunostaining of thyroid fine-needle aspirates differentiates thyroid
      papillary carcinoma from other lesions with nuclear grooves and inclusions.
AB  - BACKGROUND: Although nuclear grooves and inclusions are considered to be
      characteristic cytologic features of thyroid papillary carcinoma, a variety of
      other thyroid lesions may on occasion display these features in fine-needle
      aspiration specimens. METHODS: The authors evaluated the immunocytochemical
      staining of 16 fine-needle aspirations of thyroid papillary carcinoma and 14
      aspirations of thyroid lesions confirmed to be other than papillary carcinoma but
      that included cells with nuclear grooving and/or inclusions, comprised of
      multinodular goiter (four cases), follicular adenoma (two cases), Hurthle cell
      adenoma (two cases), pure thyroiditis (three cases), and thyroiditis with nodular
      hyperplasia (three cases). CD44 previously has been shown to be selectively
      expressed in thyroid papillary carcinoma. RESULTS: Of 16 surgically confirmed
      cases of thyroid papillary carcinoma featuring nuclear grooves and inclusions on
      fine-needle aspiration, 14 (88%) stained intensely for CD44 in a membranous
      pattern. Of the 14 nonpapillary thyroid carcinoma cases, only 1 (7%), a Hurthle
      cell adenoma, featured membranous CD44 staining. The difference in the proportion
      of cases with CD44 staining between the two groups was statistically significant
      (chi-square test, P < 0.001). CONCLUSIONS: The authors conclude that
      immunostaining for CD44 can readily be performed on thyroid fine-needle
      aspiration specimens and that, for specimens featuring nuclear grooves and
      inclusions, the presence or absence of staining for CD44 may be of value in the
      distinction between thyroid papillary carcinoma and other lesions that may share
      some of the cytologic features of papillary carcinoma.

PMID- 9196017
TI  - Fine-needle aspiration of metastatic clear cell carcinoma of the kidney:
      employment of microdissection and the polymerase chain reaction as a potential
      diagnostic tool.
AB  - BACKGROUND: The differential diagnosis of metastatic clear cell carcinoma is
      broad. To date, there are no specific immunohistochemical markers for renal cell
      carcinoma (RCC) in general use. Loss of heterozygosity (LOH) at 3p25.5, the von
      Hippel-Lindau (VHL) gene locus, is frequent in sporadic clear cell RCC. The
      authors compared LOH in primary and metastatic RCC through microdissection and
      the polymerase chain reaction (PCR) to evaluate these techniques as potential
      diagnostic tools. METHODS: The authors identified 14 patients with known clear
      cell RCC who underwent fine-needle aspiration (FNA) evaluation of presumed
      metastatic lesion. Direct-visualization microdissection was performed from
      archival histologic glass slides of the primary neoplasm and the adjacent normal
      kidney parenchyma. Malignant cell clusters were microdissected from archival FNA
      slides of metastatic lesions. The cytology slides were previously stained with
      either Diff-Quik or Papanicolaou stain. This was followed by a single-step DNA
      extraction and PCR amplification for evaluation of LOH using polymorphic markers,
      D3S1038 and D3S1110, flanking the VHL gene. RESULTS: Thirteen of the 14 cases
      contained DNA suitable for PCR in both the paraffin embedded and the FNA
      material. Eight of the 13 cases were heterozygous (informative) for the above
      markers, and 6 of these showed identical allelic loss in the primary and
      metastatic tumor for either one or both of the markers used. The remaining two
      cases did not show LOH at the VHL locus with the two polymorphic markers used.
      CONCLUSIONS: DNA from archival cytologic material stained with Papanicolaou stain
      or Diff-Quik is reliable for PCR amplification. Visually directed microdissection
      in combination with PCR has the potential to be a useful technique for
      confirmatory identification and diagnosis of metastatic clear cell RCC in
      cytologic material, because a specific genetic abnormality is present in the
      primary tumor. As characteristic genetic abnormalities are identified in various
      neoplasms, the use of this technique has the potential for conclusive evaluation
      of metastatic disease with FNA material, when used in comparison with surgical or
      cytologic material from the primary tumor. The utility of this combination of
      techniques has the potential for the molecular diagnosis of morphologically
      ambiguous cell populations.

PMID- 9196016
TI  - Computer-derived nuclear features compared with axillary lymph node status for
      breast carcinoma prognosis.
AB  - BACKGROUND: Both axillary lymph node involvement and tumor anaplasia, as
      expressed by visually assessed grade, have been shown to be prognostically
      important in breast carcinoma outcome. In this study, axillary lymph node
      involvement was used as the standard against which prognostic estimations based
      on computer-derived nuclear features were gauged. METHODS: The prognostic
      significance of nuclear morphometric features determined by computer-based image
      analysis were analyzed in 198 consecutive preoperative samples obtained by fine
      needle aspiration (FNA) from patients with invasive breast carcinoma. A novel
      multivariate prediction method was used to model the time of distant recurrence
      as a function of the nuclear features. Prognostic predictions based on the
      nuclear feature data were cross-validated to avoid overly optimistic conclusions.
      The estimated accuracy of these prognostic determinations was compared with
      determinations based on the extent of axillary lymph node involvement. RESULTS:
      The predicted outcomes based on nuclear features were divided into three groups
      representing best, intermediate, and worst prognosis, and compared with the
      traditional TNM lymph node stratification. Nuclear feature stratification better
      separated the prognostically best from the intermediate group whereas lymph node
      stratification better separated the prognostically intermediate from the worst
      group. Prognostic accuracy was not increased by adding lymph node status or tumor
      size to the nuclear features. CONCLUSIONS: Computer analysis of a preoperative
      FNA more accurately identified prognostically favorable patients than did
      pathologic examination of axillary lymph nodes and may obviate the need for
      routine axillary lymph node dissection.

PMID- 9196015
TI  - Immunocytochemical detection of p53 protein as an adjunct in cytologic diagnosis
      from pancreatic duct brushings in mucin-producing tumors of the pancreas.
AB  - BACKGROUND: In cases of mucin-producing tumor (MPT) of the pancreas, a new
      clinical entity of pancreatic tumor, it has been reported to be difficult to
      distinguish adenoma from carcinoma preoperatively. This observation caused the
      authors to develop a new method of p53 immunocytochemistry using cytologic
      samples obtained by endoscopic retrograde pancreatic duct brushing (ERPDB).
      METHODS: Fifteen cases of MPT (9 with carcinoma and 6 with adenoma) were
      examined. In all cases, histologic diagnosis was determined by surgery or
      autopsy. A wire with a small brush was pushed into the dilatated pancreatic duct
      detected by endoscopic retrograde pancreatography (ERP). Specimens obtained by
      brushing were prepared on slides and subsequently fixed with ethanol.
      Papanicolaou staining and p53 immunocytochemistry were performed simultaneously.
      The ability of conventional cytology to distinguish adenoma from carcinoma was
      compared with that of p53 immunocytochemistry. RESULTS: Five of 9 cases (56%)
      with carcinoma of MPT were correctly diagnosed by Papanicolaou staining. Two of
      four cases, classified as benign by Papanicolaou staining, expressed p53 protein.
      Overall, 7 of 9 cases (78%) with carcinoma MPT were correctly diagnosed by
      Papanicolaou staining associated with p53 immunocytochemistry. In the cases with
      adenoma MPT, all cases were classified as benign by Papanicolaou staining and no
      case positive for p53 protein was encountered. CONCLUSIONS: These results suggest
      that p53 immunocytochemistry as an adjunct in cytologic diagnosis using ERPDB may
      contribute to differentiating adenoma from carcinoma MPT of the pancreas
      preoperatively.

PMID- 9196018
TI  - Cytogenetics as an adjunct in establishing a definitive diagnosis of synovial
      sarcoma by fine-needle aspiration.
AB  - BACKGROUND: Synovial sarcomas account for up to 10% of all soft tissue sarcomas
      and are characterized by a specific chromosomal abnormality, t(X; 18)(p11.2;
      q11.2), that is observed in both monophasic and biphasic variants. METHODS: A 9
      cm suprascapular mass in a 43-year-old man and a 10-cm leg mass in a 45-year-old
      man were aspirated. Rapid evaluation of air-dried Diff-Quick-stained smears in
      both cases showed a malignant spindle cell lesion. Cytogenetic material was
      collected in RPMI 1640 tissue culture medium. Additional alcohol-fixed slides and
      cell blocks were prepared on both cases. Immunohistochemical studies were
      performed on paraffin embedded cell block sections in both cases whereas electron
      microscopic examination was performed in one case. G-banded chromosome
      preparations from tumor cells were made after short term culture using standard
      cytogenetic techniques. RESULTS: Evaluation of the smears showed densely cellular
      and tightly cohesive malignant spindle cells without discernible epithelial
      differentiation. A differential diagnosis of synovial sarcoma, leiomyosarcoma,
      malignant schwannoma, and fibrosarcoma was considered. Immunohistochemical stains
      and electron microscopy were noncharacteristic and noncontributory in
      establishing a diagnosis. However, cytogenetic results revealed a t(X; 18)(p11.2;
      q11.2) translocation, thus establishing the diagnosis of synovial sarcoma. Both
      patients were offered definitive therapy based on fine-needle aspiration (FNA)
      diagnosis only. CONCLUSIONS: FNA can be used effectively to obtain karyotypes of
      sarcomas. The specific cytogenetic abnormality associated with synovial sarcoma
      provides an opportunity to make definitive diagnoses using a combination of FNA
      and cytogenetics, obviating open surgical biopsy preceding therapy.

PMID- 9196019
TI  - The FHIT gene, a multiple tumor suppressor gene encompassing the carcinogen
      sensitive chromosome fragile site, FRA3B.

PMID- 9196020
TI  - Contribution of oncogenes and tumor suppressor genes to myeloid leukemia.

PMID- 9196021
TI  - The IGF-I receptor in cell growth, transformation and apoptosis.

PMID- 9196022
TI  - The adenomatous polyposis coli (APC) tumor suppressor.
AB  - Defects in the APC gene are inarguably linked to the progression of colon cancers
      that arise both sporadically and through the transmission of germline mutations.
      Genetic evidence from humans and mouse models suggest that APC is a classic tumor
      suppressor in that both alleles likely require inactivation for tumor growth to
      ensue. Nearly all of the mutations, germline and somatic, result in premature
      termination of the single polypeptide chain, normally consisting of 2843 amino
      acids. Several definable motifs have now been mapped to the linear amino acid
      sequence of the APC polypeptide. These include an oligomerization domain,
      armadillo repeats, binding sites for beta-catenin, the human discs large protein,
      microtubules, and other proteins of unknown function. Inactivation of APC in
      cancer is likely due to loss of function(s) normally associated with the deleted
      protein structure.

PMID- 9196023
TI  - The control and execution of programmed cell death: an update.

PMID- 9196024
TI  - The N-terminal Z repeat 5 of connectin/titin binds to the C-terminal region of
      alpha-actinin.
AB  - Connectin/titin, a 3000 kDa protein, links the Z line to the myosin filament in
      striated muscle sarcomeres. Using the yeast two-hybrid system, the present work
      shows that the N-terminal Z repeat 5 region (amino acids 447-472) of connectin
      binds to the C-terminal region (amino acids 825-897) of alpha-actinin, the main
      constituent of the Z line.

PMID- 9196025
TI  - Identification and characterization of a novel monocyte/macrophage
      differentiation-dependent gene that is responsive to lipopolysaccharide,
      ceramide, and lysophosphatidylcholine.
AB  - A novel differentiation-dependent cDNA (DIF-2) has been isolated from human
      mononuclear phagocytes by differential display. The full-length cDNA was cloned
      and sequenced. DIF-2 consists of 156 amino acids and has a predicted isoelectric
      point of 8.84. The mRNA is expressed in freshly isolated monocytes and is
      downregulated significantly when monocytes are subjected to differentiation. A
      similar differentiation-dependent downregulation is observed in normal
      hepatocytes compared to undifferentiated HepG2 cells. The mRNA expression in
      monocytes is sensitive to lipopolysaccharide and ceramide which both strongly
      increase DIF-2 transcription, while lysophosphatidylcholine results in a weaker
      upregulation of DIF-2 expression. A DIF-2 homologous gene has been previously
      isolated from mouse fibroblasts and was shown to be a serum growth factor
      inducible immediate early gene. Our results indicate that DIF-2 represents a gene
      which is regulated in differentiation processes and strongly responsive to
      lipopolysaccharide, ceramide and lysophosphatidylcholine.

PMID- 9196026
TI  - The genes encoding geranylgeranyl transferase alpha-subunit and transglutaminase
      1 are very closely linked but not functionally related in terminally
      differentiating keratinocytes.
AB  - We report here the entire exon/intron structure of the gene encoding the alpha
      subunit of human Rab geranylgeranyl transferase (RABGGTA) gene, which is
      positioned in a tandem head-to-tail arrangement with the transglutaminase 1
      (TGM1) gene, and its polyadenylation signal sequence is located just 2.3 kbp
      upstream of the capsite of TGM1. Even though TGM1 and RABGGTA have different
      functions, their close localization raised the question as to whether they are
      functionally related in the epidermis. To address this question, we have studied
      the expression of the two genes by RT-PCR in normal human epidermal keratinocytes
      cultured under various differentiation conditions. While the expression of the
      TGM1 gene is markedly affected by the calcium concentration of the medium, all
      trans retinoic acid, vitamin D3, and TPA treatment, the expression of the RABGGTA
      gene was unaffected by these reagents. Taken together, even though these two
      genes are unusually closely linked, they are not functionally related in the
      terminal differentiation program of epidermal keratinocytes.

PMID- 9196028
TI  - A domain distinct from nucleoplasmin's nuclear localization sequence influences
      its transport.
AB  - We constructed mutants of the prototypical, nuclear-accumulating protein
      nucleoplasmin and used them in both in vivo and in vitro nuclear transport assays
      to search for transport-influencing domains distinct from this protein's
      recognized nuclear localization sequence. We identified the polyglutamic acid
      tract on the amino flank of the nuclear localization sequence as being involved
      in two stages of nuclear transport. This poly-glu tract is required for the
      facilitated translocation of nucleoplasmin through the nuclear pore complex, and
      it also enhances the subsequent binding of nucleoplasmin within the nucleus.

PMID- 9196027
TI  - 1,25-dihydroxyvitamin D3 regulates the expression of N-myc, c-myc, protein kinase
      C, and transforming growth factor-beta2 in neuroblastoma cells.
AB  - 1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) alters the proliferation of
      neuroblastoma cells in culture in part via a nerve growth factor (NGF)-mediated
      pathway. This suggests that factors other than NGF also play a role in the growth
      arrest induced by 1,25(OH)2D3. To more fully characterize the effect of
      1,25(OH)2D3 on neuroblastoma cells, we treated the cells with 10(-8) M
      1,25(OH)2D3 and examined the cells for changes in the expression of N-myc, c-myc,
      transforming growth factor-beta2 (TGF-beta2), and protein kinase C (PKC)
      activity. Our results show that 1,25(OH)2D3 causes a decrease in the expression
      of N-myc and c-myc, as well as a two-fold increase in total PKC activity and a
      dose-dependent increase in TGF-beta2 expression. These results show that
      1,25(OH)2D3 regulates the expression of growth-regulatory factors other than NGF
      in neuroblastoma cells and that 1,25(OH)2D3 influences the growth of neural cells
      via multiple growth regulatory pathways.

PMID- 9196029
TI  - The origin and turnover of D-serine in brain.
AB  - The origin of D-serine was investigated using microdialysis probes to administer
      radiolabeled glucose, glycine, and L-serine directly into rat brain. In these
      experiments the labeling of D-serine was found to be determined only by the
      radioactivity present in the L-serine pool, regardless of the precursor employed,
      indicating that L-serine is the direct precursor of the D-isomer. Its rate of
      synthesis was 4.6 +/- 1.2 %/h; 9.2 nmol/g/h). This rate of synthesis is in
      agreement with that found in the mouse after a loading dose of intraperitoneally
      injected L-[3H]-serine (4.1 %/h). These rates are also consistent with the
      degradation rates of D-serine in rat and mouse brain, determined in pulse
      labeling experiments (4.1 and 3.8 %/h, respectively). Synthesis within the brain
      from L-serine therefore is adequate to account for the turnover of the brain D
      serine pool: contributions from other sources, including the diet, must be
      minimal. Independence from dietary sources was also demonstrated by the failure
      of labeled D-serine administered in the drinking water to label the brain pool
      unless very high doses were given. These results suggest that D-serine in the
      brain is formed directly by the racemization of L-serine.

PMID- 9196030
TI  - The herpes simplex virus-1 glycoprotein E (gE) mediates IgG binding and cell-to
      cell spread through distinct gE domains.
AB  - Herpes simplex virus-1 (HSV-1) glycoprotein E (gE) is a multifunctional protein
      capable of both binding the Fc portion of IgG and mediating cell-to-cell spread
      of HSV-1. Here we report that the domain on gE involved in IgG binding is
      distinct from the domain involved in mediating cell-to-cell spread. To do this we
      have used five mutants of the HSV-1 strain NS: NS-gE(null), a gE deletion virus;
      rNS-gE(null), a gE rescued virus; NS-gE339, a gE mutant virus with a four amino
      acid insert at position 339; rNS-gE339, a gE rescue of NS-gE339; and NS-gE406, a
      gE mutant virus with the same four amino acids inserted at position 406. Using
      IgG coated sheep red blood cells in rosetting assays, we show that the NS-gE339
      does not bind IgG, yet retains the ability to mediate normal cell-to-cell spread.
      These results demonstrate that the gE domain involved in IgG binding differs from
      the domain involved in cell-to-cell spread.

PMID- 9196031
TI  - Stretch-induced MAP kinase activation in cardiomyocytes of angiotensinogen
      deficient mice.
AB  - The renin-angiotensin system plays an important role in the hypertrophic
      responses in cardiac myocytes through the activation of signal transduction
      pathways and expression of oncogenes. In the present study, we examined
      mechanical stretch-induced activation of mitogen-activated protein kinases (MAP
      kinases) using cultured cardiac myocytes derived from neonatal angiotensinogen
      gene deficient mice (Agt-/-) and neonatal wild type mice (Agt+/+). Within 2
      minutes of being added to cardiac myocytes, angiotensin II activated MAP kinases
      and the response was completely blocked by pretreatment of the cardiac myocytes
      with CV-11974, a selective antagonist of angiotensin II type 1 receptors.
      Interestingly, mechanical stretch resulted in significantly greater activation of
      MAP kinases in Agt-/- cardiac myocytes than in Agt+/+ cardiac myocytes. CV-11974
      failed to suppress the stretch-induced activation of MAP kinases in Agt-/-
      cardiac myocytes while it inhibited the activation in Agt+/+ cardiac myocytes.
      BQ123, an endothelin type A receptor antagonist, had no effect on stretch-induced
      activation of MAP kinases in cardiac myocytes from either mouse strain. These
      results suggest that cardiac RAS is important for stretch-induced MAP kinase
      activation in Agt+/+ cardiac myocytes; however, angiotensin II is not
      indispensable for mechanical stretch-induced activation of MAP kinases in Agt-/-
      cardiac myocytes.

PMID- 9196032
TI  - Tyrosine phosphorylation of p38 but not extracellular signal-regulated kinase in
      normal human neutrophils stimulated by tumor necrosis factor: comparative study
      with granulocyte-macrophage colony-stimulating factor.
AB  - We investigated the cytokine-specific involvement of two members of the
      microtubule-associated protein kinase family, extracellular signal-regulated
      kinase (ERK)(1 and 2) and p38, in normal human neutrophils. Both tumor necrosis
      factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      induced tyrosine phosphorylation of a 42-kDa protein in human neutrophils, though
      the time course of its phosphorylation and its band pattern in electrophoresis
      differed for each of the cytokines. In addition, GM-CSF, but not TNF, induced a
      mobility shift of 42-kDa ERK2 in human neutrophils. By using immunoprecipitation
      followed by immunoblotting, we clarified that GM-CSF, but not TNF, induced
      tyrosine phosphorylation of ERK2 and that TNF, but not GM-CSF, induced tyrosine
      phosphorylation of p38. Results of a combined stimulation study showed that
      tyrosine phosphorylation of ERK2 and that of p38 do not interfere or interact
      with each other at least in human neutrophils. These results indicate cytokine
      specific involvement and an independent activating system of ERK and p38 in
      normal human neutrophils stimulated by two cytokines which share many biological
      activities in these cells.

PMID- 9196034
TI  - Synthesis of Cr(IV)-GSH, its identification and its free hydroxyl radical
      generation: a model compound for Cr(VI) carcinogenicity.
AB  - Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as
      an intermediate, toxic, carcinogenic species, but direct chemical evidence has
      been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr
      and few Cr(IV)-based compounds are known that can be used as a model compound
      containing a biological ligand. This study reports the isolation of such a stable
      Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction
      of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits g
      = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in
      the powder form. Magnetic susceptibility measurements showed that the compound
      has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion
      has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex
      is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in
      aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced
      it, indicating that the .OH radical was generated via a Fenton-like reaction,
      H2O2 being generated as an intermediate in the reduction of molecular oxygen.
      Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the
      generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a
      deferoxamine-derived free radical was generated as shown by EPR measurements. The
      results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)
      induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study
      the role of Cr(IV) in this mechanism.

PMID- 9196033
TI  - Single molecule imaging of fluorophores and enzymatic reactions achieved by
      objective-type total internal reflection fluorescence microscopy.
AB  - Imaging of single fluorescent molecules has been achieved in a relatively simple
      manner using objective-type total internal reflection fluorescence microscopy
      (TIRFM). Switching from epi-fluorescence microscopy to objective-type TIRFM was
      achieved by translation of a single mirror in the system. Clear images of single
      molecules of an orange fluorescent dye, Cy3, were obtained with a fluorescence-to
      background ratio of 12, using a conventional high aperture objective (PlanApo,
      100 x, NA 1.4) with ordinary coverslips and immersion oil. This method allowed
      visualization of single molecules under scanning probe microscopes. Taking
      advantage of the technique of single molecule imaging, individual ATP turnovers
      have been visualized with a fluorescent ATP analogue, Cy3-ATP, using a simple
      experimental strategy. Clear on/off signals were obtained that correspond to the
      association and dissociation of single Cy3-ATP/ADP molecules with a single myosin
      head molecule. This method will allow a variety of single-molecular assays of
      biomolecular functions to be performed using fluorescently labeled substrates,
      ligands, messengers, and biologically active molecules. Thus, the present
      technique provides a simple yet powerful and universal tool for researchers to
      probe the events of single molecules.

PMID- 9196035
TI  - Purification of a vascular apoptosis-inducing factor from hemorrhagic snake
      venom.
AB  - Hemorrhagic snake venom induces apoptosis in vascular endothelial cells
      specifically. We report here the purification of an apoptosis-inducing factor
      from the venom of the rattlesnake Crotalus atrox. The purified factor was a
      homodimeric protein with a molecular mass of 110 kD and an isoelectric point of
      8.5. When exposed to the factor, vascular endothelial cells in culture died, with
      the characteristic features of apoptosis, such as fragmentation of cells and
      cleavage of DNA into fragments that yielded a characteristic ladder pattern upon
      electrophoresis. The activity seemed to be specific to endothelial cells. This
      factor may prove to be a useful tool for studies of the molecular mechanisms of
      vascular apoptosis.

PMID- 9196036
TI  - Molecular cloning of a rat 49-kDa TBP-interacting protein (TIP49) that is highly
      homologous to the bacterial RuvB.
AB  - TBP as a central component in transcriptional regulation can form complexes with
      various regulatory factors. Using histidine-tagged TBP for affinity-purification
      of TBP-bound proteins, we isolated a 49-kD protein termed TBP-interacting protein
      49 (TIP49) from rat liver nuclear extracts. We cloned the entire cDNA of TIP49
      encoding a novel polypeptide of 456 amino acids, and thereafter established an
      FM3A cell line that constitutively expressed an epitope-tagged TBP.
      Immunoprecipitation analysis of the cell extracts indicated that TIP49 and TBP
      were present in an identical complex. Interestingly, the amino acid sequence of
      TIP49 exhibited high similarity to those sequences of the RuvB bacterial
      recombination factors which direct branch migration of the Holliday junction and
      contain the Walker A and B motifs responsible for ATP binding and ATP hydrolysis.
      These findings suggest that TIP49 is a putative ATP-dependent DNA helicase.

PMID- 9196037
TI  - Transient loss of alphaB-crystallin: an early cellular response to mechanical
      stretch.
AB  - Human trabecular meshwork (HTM) is distended and stretched with increases in
      intraocular pressure. During this stretching, there is a rearrangement of actin
      filaments. The HTM cells express alpha B-crystallin, a small heat shock protein
      that may have a role in the stabilization and regulation of the cytoskeleton in
      mammalian cells. The levels of alpha B-crystallin were examined in trabecular
      meshwork cells after mechanical stretch. Human TM primary cell cultures, plated
      onto silicone sheets, were subjected to a single 10% linear stretch and samples
      were prepared at various times after stretch for immunoblotting or Northern
      blotting. Immunoblots of total protein extracts with antibody specific for alpha
      B-crystallin detected a 26% decrease of cellular alpha B-crystallin levels within
      2 minutes. After 1 hour alpha B-crystallin levels had decreased 90% compared to
      control cells. The levels of alpha B-crystallin began to recover in cells
      stretched for 2 hours and returned to initial levels by 24 hours. Northern blots
      probed with alpha B-crystallin exon III cDNA detected a transcript of 0.65 kb in
      human TM cells and the levels of the alpha B mRNA remained constant during alpha
      B-crystallin protein decrease. Later, levels of the 0.65 kb transcript of alpha B
      crystallin increased during the cellular recovery. These results suggest that
      decreased levels of alpha B-crystallin after mechanical stretch were probably not
      due to transcriptional changes but rather to increased degradation of alpha B
      crystallin protein. An increase in mRNA levels may play a role in the recovery of
      alpha B-crystallin during reorganization of the cytoskeleton and attachment to
      the substratum. These data raise the possibility of a specific proteolysis of
      alpha B-crystallin protein in cells after a physiological challenge.

PMID- 9196038
TI  - Genistein directly induces cardiac CFTR chloride current by a tyrosine kinase
      independent and protein kinase A-independent pathway in guinea pig ventricular
      myocytes.
AB  - With one-suction electrode voltage-clamp technique, we demonstrated that
      genistein, a tyrosine kinase (TK) inhibitor, could directly activate cystic
      fibrosis transmembrane regulator (CFTR) chloride current in guinea pig
      ventricular myocytes. The activation showed concentration-dependent effect with
      the estimated IC50 of 39.7 microM. Tyrphostin 51, another TK inhibitor, had no
      effect, suggesting that genistein's effect might be unrelated to TK inhibition.
      After the chloride current had been activated by the maximally elevated
      intracellular cAMP content by saturating concentration of isoproterenol,
      forskolin and IBMX, genistein could further enhance the current. Pre-treatment
      with saturating concentration of a specific protein kinase A (PKA) inhibitor, H
      89, or other protein kinase inhibitors H-8 and H-9 in the perfusate or
      intracellularly could not prevent the activation of the current by genistein,
      suggesting a PKA-independent activity. Furthermore, saturating concentration of
      calyculin A, a specific inhibitor of phosphotase 1 and 2A, in the perfusate or
      intracellularly could not block genistein's action. It is possible that genistein
      opens the channels directly or inhibits the dephosphorylation process of CFTR,
      which is not sensitive calyculin A.

PMID- 9196039
TI  - UCP3: an uncoupling protein homologue expressed preferentially and abundantly in
      skeletal muscle and brown adipose tissue.
AB  - Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters which
      dissipate the proton gradient, releasing stored energy as heat. UCP1 is expressed
      exclusively in brown adipocytes while UCP2 is expressed widely. We now report the
      molecular cloning of a third uncoupling protein homologue, designated UCP3. At
      the amino acid level, hUCP3 is 71% identical to hUCP2 and 57% identical to hUCP1.
      UCP3 is distinguished from UCP1 and UCP2 by its abundant and preferential
      expression in skeletal muscle in humans, and brown adipose tissue and skeletal
      muscle in rodents. Since skeletal muscle and brown adipose tissue are believed to
      be important sites for regulated energy expenditure in humans and rodents,
      respectively, UCP3 may be an important mediator of adaptive thermogenesis. Since
      UCP3 is minimally expressed in human heart and other critical organs, it is a
      promising target for anti-obesity drug development aimed at increasing
      thermogenesis.

PMID- 9196040
TI  - Interaction of p59fyn with interferon-activated Jak kinases.
AB  - During IFN alpha stimulation, p59(fyn) associates with the Type I IFNR-associated
      Tyk-2 kinase in several human hematopoietic cell lines in vivo. This interaction
      is direct, and is mediated by the SH2 domain in p59(fyn), as shown by binding
      studies using glutathione-S-transferase fusion proteins and far western blots.
      Furthermore, in response to IFN alpha-treatment of cells, the SH2 domain of Fyn
      interacts with the Tyk-2-associated c-cbl proto-oncogene product. In a similar
      manner, during IFN gamma stimulation, p59(fyn) associates via its SH2 domain with
      the activated form of the IFN gamma-dependent Jak-2 kinase. These data suggest
      that p59(fyn) is a common element in IFN alpha and IFN gamma signaling, and is
      selectively engaged by the Type I or II IFN receptors via specific interactions
      with distinct Jak kinases.

PMID- 9196041
TI  - Chronic high-fat feeding and middle-aging reduce in an additive fashion Glut4
      expression in skeletal muscle and adipose tissue.
AB  - The interaction of middle-aging and chronic high-fat feeding on glucose transport
      in skeletal muscle and adipose tissue was examined. To this end, we studied the
      effects of 6 month treatment with a high-fat diet in 12-month old rats. Chronic
      high-fat feeding led to a substantial reduction in GLUT4 glucose transporter
      expression both in adipose tissue and in skeletal muscle, which was additive to
      the reduction in GLUT4 protein content detected in aged rats. In parallel, the
      high-fat diet led to a reduced insulin-stimulated glucose transport in the
      incubated soleus muscle and isolated adipocytes; insulin resistance induced by
      high-fat feeding was superimposed to the decreased insulin response detected in
      aged rats. Different mechanisms were responsible for GLUT4 repression in response
      to high-fat feeding or aging in skeletal muscles and adipose tissue.

PMID- 9196043
TI  - Rapid activation of MAP kinase by estrogen in the bone cell line.
AB  - We examined the effect of estrogen on mitogen-activated protein kinase (MAPK) in
      osteoblastic cells. Rat ROS 17/2.8 cells were exposed to 17beta-estradiol (E2)
      and MAPK activity in the cells was measured by an in vitro phosphorylation assay.
      E2 treatment caused a rapid and transient MAPK activation within 5 min. Insulin
      like growth factor-I, which acts via their membrane receptors, caused a similar
      effect, but it required 10 min to reach the maximum level. Western blot analyses
      with anti-MAPK and anti-phosphotyrosine antibodies demonstrated that the E2
      activation of MAPK was accompanied by phosphorylation of the enzyme. The
      concentration range (10 nM-1 pM) of E2 needed for this MAPK activation was less
      than that (1 microM-0.1 nM) needed for the transcriptional activation via the
      nuclear estrogen receptor (ER). These data provide the first evidence of MAPK
      activation by E2 through phosphorylation, which may be mediated through a
      putative plasma membrane receptor in the cultured bone cells.

PMID- 9196042
TI  - Identification of macrophage migration inhibitory factor in adipose tissue and
      its induction by tumor necrosis factor-alpha.
AB  - Macrophage migration inhibitory factor (MIF) has been rediscovered as a
      proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced
      immunoregulator. A survey of tissue distribution revealed that MIF expression is
      not limited to T lymphocytes, but exists in several other tissues; however, its
      presence in adipose tissue has never been investigated. In this study, we
      examined the expression of MIF in adipose tissue using the rat epididymal fat pad
      and murine 3T3-L1 adipocytes. Northern and Western blot analyses revealed the
      expression of MIF mRNA and MIF protein, respectively, in both the fat pad and the
      adipocyte cell line. In immunohistochemistry, a positive staining reaction with
      an anti-rat MIF antibody was detected largely in the cytosol of adipocytes of the
      epididymal fat pad. To examine the production and release of MIF by adipocytes,
      we examined its content in the culture medium of the 3T3-L1 adipocytes. The
      results showed that MIF content was 1.6 +/- 0.48 ng/ml (mean +/- SD) after 24 hr
      culture, and the content was increased up to 9.7 +/- 2.8 ng/ml by stimulation
      with TNF-alpha (50 nM). Since TNF-alpha produced in adipocytes is known to induce
      insulin resistance, the results suggest the possibility that MIF plays an
      important role in the mechanism of insulin resistance often observed in obesity
      and diabetes via regulation of TNF-alpha expression.

PMID- 9196044
TI  - Hydrophobic cluster analysis reveals a third chromodomain in the Tetrahymena
      Pdd1p protein of the chromo superfamily.
AB  - The protein Pdd1p (for programmed DNA degradation) links heterochromatin assembly
      and DNA elimination in Tetrahymena and has recently been identified as a new
      member of the chromo superfamily that contains two chromodomains. Using the
      sensitive bidimensional Hydrophobic Cluster Analysis (HCA) method, we have
      identified a third, highly divergent chromodomain in the Pdd1p sequence. Based on
      similarity to chromo shadow domains that mediate protein-protein interactions,
      this newly identified chromodomain may direct the binding of Pdd1p to other
      proteins. These findings suggest that Pdd1p may be the prototypical member of a
      new class in the chromo superfamily as all other members contain only one or two
      chromodomains. The results also demonstrate the power of HCA in identifying
      relationships which are not detected by conventional methods of sequence
      analysis.

PMID- 9196045
TI  - Regulation of fowl sperm flagellar motility by protein phosphatase type 1 and its
      relationship with dephosphorylation of axonemal and/or accessory cytoskeletal
      proteins.
AB  - The motility of demembranated fowl spermatozoa was vigorous at 30 degrees C in
      the presence of ATP, but decreased markedly following the addition of recombinant
      protein phosphatase type 1 (PP-1) supplemented with Mn2+. This inhibition was not
      restored by the addition of cAMP, within the range 1-1000 microM, but instantly
      restored by the addition of 50 ng/ml trypsin. Phosphorylation of demembranated
      fowl sperm proteins during incubation with [gamma-32P]ATP at 30 degrees C was
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
      A marked difference in phosphorylation status was observed in approximately 116,
      86, 79, 50 and 29-kDa proteins. These proteins were dephosphorylated in the
      presence of PP-1 and Mn2+ compared with those in control samples. These results
      suggest that PP-1-mediated dephosphorylation of some of these proteins of the
      axoneme and/or accessory cytoskeletal components of fowl spermatozoa may be
      involved in the inhibition of motility.

PMID- 9196046
TI  - Troglitazone has a scavenging effect on reactive oxygen species.
AB  - Troglitazone (CS-045), a newly developed antidiabetic thiazolidinedione that
      enhances insulin sensitivity, is similar in structure to several antioxidants,
      including alpha-tocopherol and probucol. The in vitro antioxidant activity of
      troglitazone has been demonstrated in alloxan-induced hyperlipoperoxidemic and
      hyperlipidemic mice. In this study, we found that troglitazone had a scavenging
      effect on reactive oxygen produced by xanthine-xanthine oxidase and generated by
      stimulated neutrophils and tends to be the radical form. Our results suggest that
      troglitazone is an antioxidant similar to alpha-tocopherol. However, under the
      same conditions, pioglitazone, another thiazolidinedione drug, did not have a
      scavenging effect. The antioxidant action of troglitazone, which is attributable
      to the similarity of its molecular structure to that of alpha-tocopherol, may be
      of benefit in preventing diabetic vascular complications, in addition to having
      hypoglycemic and hypolipidemic effects.

PMID- 9196047
TI  - Lovastatin increases surface low density lipoprotein receptor expression by
      retarding the receptor internalization rate in proliferating lymphocytes.
AB  - We examined the effects of Lovastatin on LDL receptor (LDL-R) expression and rate
      of internalization in interleukin-2 (IL-2) expanded phytohemagglutinin-stimulated
      lymphocytes. Lovastatin increased the surface LDL-R expression, but not DiI-LDL
      uptake, by up to 30% regardless of whether cell proliferation was affected. It
      caused a dose-dependent reduction in the LDL-R internalization rate as determined
      with monensin. Lovastatin had no effect on IL-2 receptor internalization.
      Inhibition of DNA synthesis by hydroxyurea or protein tyrosine kinase activity by
      genistein failed to affect the LDL-R internalization rate. Co-incubation of cells
      with Lovastatin and mevalonate or LDL completely restored the rate of LDL-R
      internalization. We conclude that Lovastatin increases the apparent surface LDL-R
      expression by retarding the rate of LDL-R internalization. The effect is mediated
      through the mevalonate pathway but not the anti-mitogenic property of Lovastatin.

PMID- 9196048
TI  - Relaxation of imprinting of human insulin-like growth factor II gene, IGF2, in
      sporadic breast carcinomas.
AB  - Breast cancer is the most frequent malignancy in women and genetically
      heterogeneous, and a variety of genetic lesions have been identified that tend to
      accumulate during the disease progress. In breast cancer, loss of heterozygosity
      (LOH) has been described in the critical regions of chromosomes 11p15 and 11q22
      23. Genomic imprinting is defined as gamete specific modification causing
      differential expression of the two alleles of a gene, in somatic cells. Human
      insulin like growth factor II gene (IGF2), located on chromosome 11p15, the same
      region on which LOH frequently occurred in breast cancer, has been recently
      identified as a genomic imprinting gene expressing preferentially paternal
      allele. To determine whether loss of IGF2 imprinting was common in breast cancer
      we studied 30 patients with sporadic breast carcinoma. A new strategy for
      detecting intragenic Apa I polymorphism in the exon of IGF2 was used to examine
      allele-specific expression in the breast cancer specimens by reverse
      transcription polymerase chain reaction (RT-PCR). Forty percent (12/30) of the
      breast cancer samples were identified as heterozygous for IGF2 and studied
      further. Nine of the 12 heterozygous patients showed biallelic expression of IGF2
      by cDNA-PCR, indicating relaxation of normal imprinting at this chromosomal
      locus. Conclusively, aberrant imprinting of IGF2 in 30% of the breast cancer
      patients tested provides strong evidence that pathological loss or relaxation of
      IGF2 imprinting plays an important role in either tumorigenesis or cytokine
      dysregulation for breast cancer cells.

PMID- 9196049
TI  - Identification of four novel human phosphoinositide 3-kinases defines a multi
      isoform subfamily.
AB  - Phosphoinositide (PI) 3-kinases have critical roles in diverse cellular
      signalling processes and in protein trafficking. This suggests that like other
      intracellular signalling molecules, e.g., phospholipase C and protein kinase C,
      there might be a large family of PI 3-kinase isoforms with the individual members
      having discrete signalling roles. Reverse transcription-polymerase chain reaction
      methods, using degenerate oligonucleotide primers against the lipid kinase
      consensus region, revealed eight sequences from human cDNA containing a high
      degree of identity to the family of PI 3-kinases. The sequences obtained included
      the previously described p110 alpha, p110 beta, and p110 gamma isoforms and
      HsVps34. Additionally, we have identified four novel sequences which are related
      to PI 3-kinases. Three of the novel sequences would appear to form a distinct sub
      family of PI 3-kinases. We report the expression of these novel PI 3-kinases in
      human tissues and in cells derived from normal breast.

PMID- 9196050
TI  - Glycogen-storage disease type II (acid maltase deficiency): identification of a
      novel small deletion (delCC482+483) in French patients.
AB  - Glycogen-storage disease type II (GSD II, acid maltase deficiency, Pompe's
      disease) is caused by defects in the lysosomal acid alpha-glucosidase (GAA) gene.
      Clinically, patients with the severe infantile form of GSD II have muscle
      weakness and cardiomyopathy eventually leading to death before the age of two
      years. Patients with the juvenile or the adult form of GSD II present with
      myopathy with a slow progression over several years or decades. Apart from a
      common base substitution in intron1, designated IVS1(-13T-->G) and resulting in
      the aberrant splicing of exon 2, the other mutations recently discovered in the
      GAA gene are rare and often unique to single patients. In this paper, we
      identified a two-base frameshift deletion in three unrelated adult-onset GSD II
      patients. This small deletion lies in the first coding exon (exon 2) and results
      in a premature stop codon at the very 5' end of the coding sequence of the GAA
      gene. The three patients were compound heterozygotes and two of them had the
      common IVS1(-13G-->T) mutation on the second allele. We speculate that this novel
      deletion may be relatively frequent among French patients, possibly leading to
      the severe infantile phenotype of GSD II if it occurs in homozygous form.

PMID- 9196052
TI  - Two types of microsomal prostaglandin E synthase: glutathione-dependent and 
      independent prostaglandin E synthases.
AB  - Prostaglandin (PG) E synthase was found to be widely distributed in the
      microsomal fractions of rat organs. Among them, an extremely high activity was
      seen in the deferent duct (112 nmol/min x mg) and other genital accessory organs
      (10-20 nmol/min x mg). In non-genital organs, the kidney had the highest activity
      (8 nmol/min x mg). Most of the PGE synthase activity in these organs required
      glutathione (GSH). In contrast, the enzyme activity in the heart, spleen, and
      uterine microsomes did not require GSH for its catalytic activity. In view of
      these data and those of other enzymatic parameters (Km values for PGH2 or pH
      optima), we suggest that two different types of PGE synthases, GSH-dependent and
      GSH-independent enzymes, are present in microsomal fractions of rat tissues.

PMID- 9196051
TI  - Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling
      molecules during chondrogenesis and cartilage differentiation in clonal mouse EC
      cells, ATDC5.
AB  - Hedgehog (hh) family proteins appear to use the conserved targets in their
      signalling pathway including Patched (Ptc), Smoothened (Smo), and Gli. Although
      Indian hedgehog (Ihh) plays an important role in endochondral bone formation, the
      involvement of hh signalling molecules in skeletogenesis is unknown. We cloned a
      mouse (m) Smo cDNA and studied the expression patterns of Ihh, Ptc, Smo, and Gli
      mRNAs in mouse chondrogenic EC cells, ATDC5. The deduced amino acid sequence of
      mSmo consisted of 793 amino acids and was 98 and 93% homologous to the rat (r)
      Smo and human (h) Smo, respectively. In ATDC5 cells, the expression of Ihh mRNA
      paralleled that of type X collagen mRNA. Smo, Ptc, and Gli mRNAs were
      constitutively expressed throughout chondrogenesis and the subsequent cartilage
      differentiation processes except for the transient decrease in Ptc mRNA at the
      cellular condensation stage. Our data suggest that hh signalling molecules may be
      involved in chondrogenesis and cartilage differentiation in ATDC5 cells.

PMID- 9196053
TI  - Transcriptional activation of the human c-myc gene by simian virus 40 large T
      antigen without binding to p53 and RB proteins in the transient expression
      system.
AB  - Transcriptional activation of the human c-myc gene by SV40 large T antigen was
      examined using HepG2 cells by co-transfecting a T antigen expression plasmid with
      a myc-CAT construct containing the 2.3-kb upstream region from the P1 promoter
      and the P2 promoter region fused to the CAT gene. T antigen increased the basal
      activity of the P2 promoter region containing the E2F binding site, but both the
      P2 promoter region and the upstream region from the P1 promoter were important
      for overall activation by T antigen. CAT assay using mutated T antigen lacking
      p53 or the RB binding site indicated that p53 or RB was not mainly involved in
      transcriptional activation of the c-myc gene. It appears that activation of the c
      myc gene by T antigen is probably dependent upon E2F and a cellular factor
      through a mechanism which is independent of binding of T antigen to p53 and RB.

PMID- 9196054
TI  - Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death
      in Parkinson's disease.
AB  - The oxidative stress theory, the mitochondrial (mt) hypothesis, and the apoptosis
      hypothesis are proposed as the cause of neuronal cell death in Parkinson's
      disease (PD). However, the direct link between them has remained unknown.
      Recently, the mt control of nuclear apoptosis is documented that collapse of mt
      transmembrane potential due to energy crisis leads to release of apoptotic
      protease activating-factors into cytosol and subsequently nuclear DNA
      fragmentation. However, an endogenous factor responsible for the energy crisis
      under physiological conditions is missing. Here we report the missing factor as
      that mtDNA in the striatum of a parkinsonian patient fragments into 134 types of
      deleted pieces, being detected by the total detection system for mtDNA deletion.
      The system has documented that the mtDNA is extremely susceptible to hydroxyl
      radical damage, hence to oxidative stress, enough to cause the cellular energy
      crisis. The extensive fragility of mtDNA in brain stem could link the oxidative
      stress up with the apoptotic neuronal cell-death of PD.

PMID- 9196055
TI  - B30.2-like domain proteins: a growing family.
AB  - The B30.2 domain is a conserved domain of around 170 amino acids. It is found
      associated with different protein domains: immunoglobulin domain in the case of
      butyrophilin and Ring Finger domain in the case of Ret Finger Protein. B30.2
      should therefore be considered a migratory domain. We here report new members of
      these families as well as new protein families having the B30.2 domain, and we
      tentatively propose a general function for this domain.

PMID- 9196056
TI  - Evidence for a dual control of macroautophagic sequestration and intracellular
      trafficking of N-linked glycoproteins by the trimeric G(i3) protein in HT-29
      cells.
AB  - The trimeric G(i3) protein-dependent lysosomal-autophagic pathway is responsible
      for the degradation of a pool of N-linked glycoproteins in the human colon cancer
      HT-29 cell line. Here we have followed the fate of N-glycans using HT-29 cells
      either overexpressing the wild-type G alpha(i3) protein or transfected with
      different mutants of the G alpha(i3) protein. The stabilization of N-glycans was
      dependent upon the inhibition of autophagic sequestration by either 3
      methyladenine (3-MA) or pertussis toxin (PTX). However, PTX allowed the
      processing of high-mannose glycans whereas 3-MA did not. The destabilization of
      the Golgi apparatus by brefeldin A, which interrupts the intracellular
      trafficking of N-linked glycoproteins along the secretory pathway, did not
      interfere with the macroautophagic pathway. These results suggest that the
      lysosomal-autophagic pathway is not dependent upon the integrity of the Golgi
      apparatus and points to differences between the molecular properties of two
      membrane flow processes (macroautophagy, exocytic pathway) controlled by the
      trimeric G(i3) protein.

PMID- 9196057
TI  - Gastric inhibitory polypeptide activates MAP kinase through the wortmannin
      sensitive and -insensitive pathways.
AB  - The signal transduction pathways of a cloned human gastric inhibitory polypeptide
      (GIP) receptor have been investigated in CHO cells stably expressing this
      receptor. Exposure of GIP receptor expressing cells to GIP significantly
      increased MAP kinase activity. Time course analysis showed that a rapid and
      marked increase in MAP kinase activation was detected and that this activation
      reached maximal levels 10 min after the addition of GIP. Dose-response analysis
      showed that GIP activated MAP kinase activity in a dose-dependent manner with an
      ED50 value of 5.9 x 10(-10) M of GIP. Wortmannin, a potent inhibitor of
      phosphatidylinositol 3-kinase (PI3-kinase), partially inhibited GIP-induced MAP
      kinase activation, suggesting that GIP activates MAP kinase through two
      different, wortmannin-sensitive and -insensitive pathways. It has been
      demonstrated that in CHO cells cAMP attenuates MAP kinase activity by inhibiting
      Raf-1. Since GIP elevates intracellular cAMP, we examined the effects of cAMP on
      MAP kinase activation. Interestingly, forskolin, which increased intracellular
      cAMP levels, significantly inhibited MAP kinase activation by GIP, but did not
      affect MAP kinase activation by GIP in the presence of wortmannin, suggesting
      that the wortmannin-sensitive pathway activates an MAP kinase cascade at or above
      the level of Raf-1 and that the wortmannin-insensitive pathway activates an MAP
      kinase cascade below the level of Raf-1. These findings demonstrate that the GIP
      receptor is linked to the MAP kinase cascade via at least two different pathways.

PMID- 9196058
TI  - Complementation analysis of fibroblasts from peroxisomal fatty acid oxidation
      deficient patients shows high frequency of bifunctional enzyme deficiency plus
      intragenic complementation: unequivocal evidence for differential defects in the
      same enzyme protein.
AB  - In the last few years many patients have been reported with a defect in
      peroxisomal fatty acid beta-oxidation of unknown origin. Using a combined
      approach based on direct activity measurements of straight-chain acyl-CoA oxidase
      and complementation analysis after somatic cell fusion of fibroblasts, we have
      now classified 13 patients into 4 distinct groups representing different gene
      defects. Remarkably, we found intragenic complementation in group 2 so that group
      2 is in fact made up of 3 distinct subgroups. The underlying basis for this
      peculiar phenomenon probably has to do with the fact that bifunctional protein
      harbors two catalytic activities including enoyl-CoA hydratase and 3-hydroxyacyl
      CoA dehydrogenase. In group 2A enoyl-CoA hydratase and 3-hydroxyacyl-CoA
      dehydrogenase are defective whereas in group 2B and 2C either the hydratase or 3
      hydroxyacyl-CoA dehydrogenase component of the bifunctional protein is deficient.

PMID- 9196059
TI  - Lung "surfactant convertase" is a member of the carboxylesterase family.
AB  - The extracellular conversion of lung surfactant from tubular myelin to the small
      vesicular form has previously been shown to require a serine-active enzyme called
      "surfactant convertase." In the present study, a 72kD serine-active enzyme
      previously identified in mouse lung alveolar lavage and having convertase
      activity was partially sequenced. Sixty-eight residues obtained from amino acid
      sequencing of this protein show that it is a new member of the mouse
      carboxylesterase family (EC 3.1.1.1). The 72kD lung protein also has esterase
      activity. A commercial esterase of the same family was able to reproduce
      surfactant convertase bioactivity in vitro, unlike several serine proteinases
      previously tested. We conclude that surfactant convertase is a carboxylesterase
      which mediates a biochemical step in the extracellular metabolism of surfactant.

PMID- 9196060
TI  - Genomic organization and complete nucleotide sequence of the TMEM1 gene on human
      chromosome 21q22.3.
AB  - TMEM1 (EHOC-1) gene encodes a putative transmembrane protein and is located on
      human chromosome band 21q22.3. Analysis of a 122,638-bp genomic sequence revealed
      that TMEM1 gene consists of 23 exons spanning approximately 94 kb and is
      transcribed in the direction of centromere to telomere. The 5' region of the
      TMEM1 gene was associated with a CpG island and the 3' end of the TMEM1 gene was
      mapped just proximal to the 5' end of the neighboring gene PWP2. We determined
      that the TMEM1 gene encodes a protein of 1,259 amino acids, which is 69-amino
      acids longer than the previously reported sequence. Since TMEM1 gene is
      considered to be a candidate for genetic disorders mapped in the 21q22.3 region,
      the information including complete nucleotide sequence and genomic organization
      of the TMEM1 gene should be invaluable for the mutation analysis of the
      corresponding genetic disorders.

PMID- 9196061
TI  - Expression of the proliferation-related Ki-67 mRNA in the early development of
      murine embryo.
AB  - In a search for early lymphoid-specific genes, we isolated a cDNA clone (LL7)
      encoding a murine homologue of Ki-67 protein, a proliferation-related nuclear
      antigen. LL7 transcript appears preferentially in lymphoid organs as the bone
      marrow, spleen, and the thymus. Here, we studied the expression of murine Ki-67
      (mKi-67) mRNA among various organs or tissues during the early development of
      fetus. In fetus, mKi-67 mRNA appears developmentally as early as day 11 and is
      expressed maximally at day 15. In situ hybridization on the section revealed that
      the expression of mKi-67 mRNA is preferential in the area of active organ
      formation such as neurological system and the fetal liver. These results suggest
      that mKi-67 plays an important role in the proliferation of early embryonic
      precursor cells of neurological and immune systems.

PMID- 9196062
TI  - Inhibitory action of sphingosine or ceramide on amylase secretion from isolated
      rat pancreatic acini.
AB  - Sphingosine and ceramide, products of sphingomyelin hydrosis by sphingomyelinase,
      have recently been regarded as second messengers for cell biological actions. On
      the other hand, exocrine pancreas is a typical organ to perform regulatory
      secretion of digestive enzymes, depending upon extracellular signals. We
      investigated the effects of sphingosine or ceramide on amylase secretion from
      isolated rat pancreatic acini. Either sphingosine or cell-permeable ceramide
      inhibits CCK8- or carbachol-induced enzyme secretion from isolated rat pancreatic
      acini in a dose-dependent manner. Sphingosine or ceramide itself does not affect
      basal amylase secretion from the acini. Ceramide also inhibits NaF-induced
      amylase secretion, indicating that it acts post the activation of receptor-linked
      GTP-binding protein. In our experiments, ceramide inhibited Ca2+ ionophore
      induced amylase secretion, but not phorbol ester-induced secretion. These results
      indicate that ceramide affects secretory processes post intracellular Ca2+
      mobilization in the exocrine pancreas.

PMID- 9196063
TI  - Taxol inhibits opioid binding on T47D human breast cancer cells.
AB  - In the T47D human breast cancer cell line, Taxol was found to compete for
      ethylketocyclazocine opioid binding (IC50 3.3 pM). In contrast, no interaction of
      the drug with [3H]diprenorphine binding occurred. Binding was multiphasic, in the
      absence of colchicine (10[-6] M), but monophasic in its presence, indicating an
      involvement of the cytoskeleton in this process. Alignment of Taxol binding
      domains on alpha and beta tubulin with the kappa opioid site revealed homology of
      these sites with the first extracellular loop of the receptor. These results
      indicate a possible new action of Taxol, indicating for the first time a membrane
      action of the agent.

PMID- 9196064
TI  - Identification of the human aldolase A gene as the first induced target for the
      TR2 orphan receptor, a member of the steroid hormone receptor superfamily.
AB  - The human TR2 orphan receptor (TR2) is a member of the steroid/thyroid hormone
      receptor superfamily that regulates the transcription of complex gene networks
      and subsequently controls diverse aspects of growth, development, and
      differentiation. In the present study, we have found that the TR2 is one of the
      M1 site (nucleotide numbers 2017-2034, 5'-AAAAGGGCAGGGGTCATT-3') binding proteins
      of the muscle-specific pM promoter in the human aldolase A gene. Electrophoretic
      mobility shift assay (EMSA) showed a specific binding with high affinity
      (dissociation constant = 4.6 nM) between the TR2 and the M1 element. Circular
      permutation assay revealed a localized DNA flexibility induced by the TR2
      binding, and the bend angle was estimated to be 73 +/- 2 degrees. Furthermore, a
      dual-luciferase reporter gene assay demonstrated that the TR2 may enhance the
      expression of luciferase activities via the wild-type M1 site but not the mutant
      M1 element in human QM7 muscle myoblasts. In conclusion, our data represent the
      first case of demonstrating that the TR2 may serve as a transcriptional inducer
      in muscle-specific aldolase A gene expression.

PMID- 9196065
TI  - Structure and function of the iron-responsive element from human ferritin L chain
      mRNA.
AB  - We report the cloning and functional characterization of the iron responsive
      element (IRE) of human ferritin light (L) chain mRNA from a cDNA library of
      primary human T lymphocytes. Comparison of this palindromic cDNA element to the
      IRE predicted from the reported genomic sequence revealed significant
      differences, resulting in a stem-loop structure with lower stability than the IRE
      of the heavy (H) chain mRNA. Nevertheless, the L subunit IRE mediated efficient
      binding of the iron regulatory protein (IRP) in a manner comparable to that of
      human ferritin H chain mRNA in vitro. In accordance with previous observations on
      H form transcripts, the cis-acting regulatory IRE motif of human ferritin L chain
      mRNA was capable of repressing translation under iron deprivation but permitted
      mobilization of the transcripts into polysomes following iron repletion in vivo.

PMID- 9196066
TI  - Chronic stimulation differentially modulates expression of mRNA for
      dihydropyridine receptor isoforms in rat fast twitch skeletal muscle.
AB  - This study examined the effects of low frequency chronic stimulation on
      expression of the mRNA encoding the two isoforms of the alpha1 subunit of the
      dihydropyridine receptor (DHPR) calcium channel, a critical component of skeletal
      muscle excitation-contraction coupling. RNase protection assay was used to
      determine alteration in isoform expression in 5-day, 9-day and 13-day chronically
      stimulated rat tibialis anterior muscle, and to compare it with soleus and
      extensor digitorum longus muscles. Low frequency chronic stimulation was
      associated not only with a significant decrease in the mRNA level of the skeletal
      isoform of the DHPR, but also with a significant increase in the mRNA level of
      the cardiac isoform of the DHPR, the overwhelming majority of which was the adult
      splice variant. Significant levels of cardiac DHPR mRNA expression were also
      found in normal adult slow twitch soleus muscle. These findings raise the
      question of a potential role for the cardiac DHPR in certain adult skeletal
      muscles.

PMID- 9196067
TI  - Purification of a regulatory subunit of type II cAMP-dependent protein kinase
      from Drosophila heads.
AB  - The cytosolic extract from Drosophila heads was separated using anion-exchange
      column chromatography. Two types of cAMP-dependent protein kinase (PKA), type I
      and type II, were detected, and type II PKA was found to be a major isozyme. The
      regulatory subunit of type II PKA (RII) was purified, and only one isoform was
      observed. The purified protein had an apparent molecular mass of 51 kDa on SDS
      gel electrophoresis. Partial amino acid sequences of the protein were almost
      identical with the RII alpha subunit of human. Since PKA has been implicated to
      be especially important for learning and memory in Drosophila, the RII subunit
      may play an essential role in the regulation of neuronal activity in the brain of
      Drosophila, and possibly in human.

PMID- 9196068
TI  - Mouse adhalin: primary structure and expression during late stages of muscle
      differentiation in vitro.
AB  - Adhalin, or alpha-sarcoglycan, is a 50-kDa glycoprotein that was originally
      characterized as a muscle membrane protein. The importance of adhalin is
      suggested by the diseases associated with its absence, notably the limb-girdle
      muscular dystrophies. However, the function of adhalin is unknown. To analyze the
      biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide
      specific antibodies to its cytoplasmic domain, and examined its expression and
      localization in vivo and in vitro. The mouse adhalin sequence was 80% identical
      to that of human, rabbit, and hamster. Adhalin was specifically expressed in
      striated muscle cells and their immediate precursors, and absent in many other
      cell types. Adhalin expression in embryonic mouse muscle was coincident with
      primary myogenesis. Its expression was found to be up-regulated at mRNA and
      protein levels during myogenic differentiation in vitro. The proper localization
      of adhalin to the muscle cell membrane was observed only in late stages of
      myotube maturation, coincident with the re-distribution of caveolin-3 and
      dystrophin. These data suggest that adhalin is highly specific for striated
      muscle and that it is linked with the formation of a fully functional muscle
      fiber.

PMID- 9196069
TI  - Presence of zinc and calcium permeant channels in the inner membrane of the
      nuclear envelope.
AB  - The nuclear envelope possesses specific ion channels that regulate the ionic
      traffic between the cytoplasm or the perinuclear space and the nucleoplasm. Using
      the patch-clamp technique to isolated rat nuclei exhibiting only the inner
      membrane of the nuclear envelope, we report the existence of calcium and zinc
      permeant channels. These channels displayed similar characteristics (conductance
      : 8 and 11 pS respectively, open time constant (3.5 ms and 3.7 ms) and close time
      constant (5.1 ms and 4.8 ms)) and were insensitive to different types of calcium
      channels blockers and to calcium concentration in the bathing solution. The exact
      role of these channels remains to define, but they may contribute to the
      regulation of intranuclear Ca++ or Zn++ dependent processes as important as cell
      proliferation or programmed cell death. Moreover, this work demonstrates that our
      nuclei preparation provides a way to study the inner membrane of the nuclear
      envelope.

PMID- 9196070
TI  - Somatostatin inhibits interleukin 6 release from rat cortical type I astrocytes
      via the inhibition of adenylyl cyclase.
AB  - Interleukin 6 is a pleiotropic cytokine produced in the central nervous system
      (CNS) that has been involved in both direct neurotrophic activities and in the
      regulation of the production of acute phase proteins both at peripheral and
      central levels. In rat cortical type I astrocytes, interleukin 6 release is under
      the control of cAMP-protein kinase A and calcium-phospholipids-protein kinase C
      systems. Somatostatin is a neuropeptide, acting as a neurotransmitter, highly
      concentrated within the CNS, where it has been involved in the modulation of
      learning and memory processes. The aim of this study was to characterize the
      effects of somatostatin on the release of interleukin 6 from rat cortical type I
      astrocytes and the intracellular mechanisms involved in this activity. Our
      results show that somatostatin, in a concentration-dependent manner, inhibited
      basal and forskolin-stimulated interleukin 6 release from rat cortical type I
      astrocytes in culture. The EC50 of the inhibitory action was calculated to be
      approximately 10 nM. Furthermore, this effect of somatostatin was completely
      abolished by pretreating cortical astrocytes with pertussis toxin that,
      uncoupling, by ADP-rybosylating, the inhibitory GTP-binding protein from the
      receptors, prevents the activation of the intracellular effectors such as the
      adenylyl cyclase enzyme. To identify the intracellular mechanism mediating the
      effects of somatostatin on the interleukin 6 release, we evaluated the peptide
      modulation of basal and stimulated intracellular accumulation of cAMP. In our
      experimental conditions somatostatin significantly inhibited both basal and
      forskolin-stimulated cAMP accumulation. Conversely, somatostatin did not affect
      the increase of interleukin 6 release induced by dibutyryl-cAMP, a
      nonhydrolizable cAMP analog that, bypassing the effects of somatostatin on
      adenylyl cyclase activity, directly activated protein kinase A. These
      observations support the hypothesis that somatostatin inhibitory activity on
      interleukin 6 release is mediated by its effects on cAMP production. Somatostatin
      analog SMS 201-995 did not affect interleukin 6 production either in basal or
      stimulated conditions. Since, SMS 201-995 was reported to bind with high affinity
      only to somatostatin receptors type 2, 3 and 5, the lack of effect of this
      compound on interleukin 6 release suggests that the inhibitory action of
      somatostatin could be mediated by the activation of either type 1 or type 4
      somatostatin receptors. In conclusion, our data demonstrate that the release of
      interleukin 6 from rat cortical type I astrocytes is inhibited by somatostatin
      through the activation of a somatostatin receptor coupled to the inhibition of
      adenylyl cyclase via a G-protein sensitive to pertussis toxin.

PMID- 9196071
TI  - Alzheimer's disease-associated presenilins 1 and 2: accelerated amyloid fibril
      formation of mutant 410 Cys-->Tyr and 141 Asn-->Ile peptides.
AB  - Mutations in the presenilin 1 gene on chromosome 14 and in the related gene on
      chromosome 1 have been identified in individuals with early-onset familial
      Alzheimer's disease. The functions of the presenilin gene products as well as the
      relation of the presenilin mutations to amyloidogenesis are unclear. Here we show
      that peptides homologous to two disease-associated mutant forms of presenilin 1
      and 2, respectively, show highly increased amyloid fibril formation as compared
      with the wild-type peptide homologues. The 410 Cys -->Tyr (S-182) 14-residue
      peptide and the 141 Asn-->Ile (E5-1) 15-residue peptide spontaneously assemble to
      fibrils of 7 to 9 nm width with strong Congophilic characteristics. Thioflavine-T
      fluorometry reveals a 7- to 18-fold higher rate of amyloid fibril formation of
      the mutant peptides as compared with the corresponding wild-type homologues. The
      results provide new insights into the mechanisms by which presenilin mutations
      lead to Alzheimer-type neuropathology: missense mutations in the presenilin genes
      may create products that are intrinsically highly amyloidogenic and directly
      involved in pathogenesis.

PMID- 9196072
TI  - Expression of transcription factors in keratoconus, a cornea-thinning disease.
AB  - Transcription factors are known to regulate gene transcription through the
      recognition and binding of specific DNA sequences in the promoter or enhancer
      regions of many genes. Keratoconus is a cornea-thinning disease in which
      upregulated expression of degradative enzymes and downregulated expression of
      protease inhibitors have been demonstrated. In view of the alteration in gene
      expression for multiple proteins, five common transcription factors, AP1, AP2,
      CREB, Sp1, and NF-kappa B were examined for their possible roles in keratoconus.
      Immunostaining experiments and Western blotting showed that Sp1 exhibited
      enhanced expression in keratoconus corneas. Increased binding of Sp1 consensus
      sequence oligonucleotides with nuclear extracts from the epithelium of
      keratoconus corneas was also seen by gel mobility shift assays. This is believed
      to be a first demonstration connecting Sp1 alteration to a human disease. The
      elevated Sp1 expression may contribute to the enzyme and inhibitor abnormalities
      found in keratoconus corneas.

PMID- 9196073
TI  - Identification of glycyrrhizin as a thrombin inhibitor.
AB  - Glycyrrhizin (GL), an anti-inflammatory compound isolated from Glycyrrhiza
      glabra, was identified as a new thrombin inhibitor: (a) It prolonged plasma
      recalcification and thrombin and fibrinogen clotting times, and (b) it inhibited
      thrombin-induced, but not collagen-, PAF- or convulxin-induced platelet
      aggregation. On the other hand, GL did not block thrombin's amidolytic activity
      upon S-2238. Furthermore, the fluorescence emission intensity of dansyl-thrombin
      was increased upon GL binding. Moreover, GL displaced hirudin as an inhibitor of
      thrombin-catalyzed hydrolysis of S-2238. Our data provide evidence that GL is a
      selective inhibitor of thrombin (the first one isolated from plants) that is able
      to exert its anti-thrombin action by interacting with the enzyme's anion binding
      exosite 1. A pharmacophoric search identified GL as a sialyl Lewis X (SLe[X])
      mimetic compound able to inhibit selectin binding to SLe(X). However, SLe(X) did
      not affect thrombin clotting activities, which indicates a lack of its
      interaction with thrombin and distinguishes both molecules. It is suggested that
      the anti-inflammatory effect of GL may be due to its effective anti-thrombin
      action.

PMID- 9196074
TI  - Some new details of the copper-hydrogen peroxide interaction.
AB  - The addition of neocuproine (NC) or bathocuproinedisulphonate at the end of the
      autooxidation of Cu(I) in phosphate buffer, pH 7.4, regenerates almost entirely
      the O2 consumed. Other chelating agents assayed, including o-phenanthroline,
      cannot replace NC in promoting the O2 formation. O2 is also produced by adding NC
      to a mixture of Cu(II) and H2O2. Concomitant with the O2 evolution, the typical
      absorbance of the (NC)2Cu(I) complex appears to account for the complete
      reduction of Cu(II) to Cu(I). It is concluded that the addition of H2O2 with
      Cu(II) produces the equilibrium Cu(II)(O2H)(-)<--> Cu(I.)O2H. Addition of NC
      shifts the equilibrium to the right side by binding Cu(I). The released O2.- then
      reacts with the remaining Cu(II) yielding, in the presence of NC, the net
      reaction of 4 NC + 2 Cu(II) + H2O2 --> 2 (NC)2Cu(I) + O2 + 2 H+. O2 is also
      released in the absence of added NC provided the H2O2 concentration is increased.
      In these conditions the Cu(II)(O2H) complex undergoes other reactions leading to
      the copper-catalysed decomposition of H2O2.

PMID- 9196076
TI  - Tissue-specific processing of the Surf-5 and Surf-4 mRNAs.
AB  - The mouse surfeit locus is an unusually tight cluster of at least six
      "housekeeping" genes that do not share any sequence homology and whose gene
      organization may play a role in gene expression. The transcription of each of the
      five well-characterized genes (Surf-1 to -5) alternates with respect to its
      neighbor(s) and no more than 159 bp separates any two adjacent genes with the
      Surf-4 and Surf-2 genes overlapping at their 3' ends by 133 bp. In this work, the
      expression of the Surf-5 and Surf-4 genes has been examined in various mouse
      tissues. In addition to the ubiquitously expressed 3.5-kb Surf-5 mRNA, a second
      alternatively spliced Surf-5 mRNA, Surf-5b, was discovered that was highly
      expressed in the brain, heart, testis, and skeletal muscle. The alternative
      splice donor site of the Surf-5b mRNA is similar to splice donor sites found in
      neuron-specific mRNAs. Surf-5b encodes a unique protein, which, like the
      ubiquitous Surf-5 protein, has been found to be primarily located in the soluble
      fraction of the cytoplasm. The expression of the Surf-5b protein was also found
      to increase in embryonal carcinoma cells differentiated into neuronal cultures.
      Although the Surf-5 gene is highly conserved through evolution, the presence of
      the Surf-5b alternative splice may be restricted to higher vertebrates. The Surf
      4 gene was ubiquitously expressed in eight different mouse tissues; however, the
      ratios of the three previously reported Surf-4 mRNAs (two of which are known to
      derive from different sites of polyadenylation) altered dramatically between
      tissues. The use of different forms of mRNA processing for regulation of tissue
      specific expression of ubiquitously expressed genes is discussed.

PMID- 9196077
TI  - Functional conservation of yeast mtTFB despite extensive sequence divergence.
AB  - Transcription of mtDNA in the yeast S. cerevisiae depends on recognition of a
      consensus nonanucleotide promoter sequence by mtRNA polymerase acting with a 40
      kDa dissociable factor known as mtTFB or Mtflp. mtTFB has been cloned and
      characterized in S. cerevisiae, but has not been studied in similar detail in any
      other organism. Although it is known that mitochondrial transcription in the
      dairy yeast, Kluyveromyces lactis, initiates within the same consensus promoter
      sequence used in S. cerevisiae, no previous studies have focused on the proteins
      involved in transcription initiation in K. lactis. In this article, we report the
      cloning of mtTFB from K. lactis and from a yeast more closely related to S.
      cerevisiae, S. kluyveri. Both novel mtTFB genes were able to substitute for the
      MTF1 gene in S. cerevisiae. Both proteins purified following expression in E.
      coli were able to support specific transcription initiation in vitro with the S.
      cerevisiae mtRNA polymerase. The S. kluyveri and K. lactis mtTFB proteins share
      only 56% and 40% identity with S. cerevisiae mtTFB, respectively. Alignments of
      the three mtTFB sequences did not reveal any regions larger than 30 amino acids
      with greater than 60% amino acid identity. In particular, regions proposed to
      show sequence similarity to bacterial sigma factors were not more highly
      conserved than other regions of the mtTFB proteins. All three yeast mtTFB genes
      lack conventional amino-terminal mitochondrial targeting sequences, suggesting
      that all three proteins may be imported into mitochondria by the same unusual
      mechanism reported for S. cerevisiae mtTFB.

PMID- 9196075
TI  - Nuclear hormone receptors inhibit matrix metalloproteinase (MMP) gene expression
      through diverse mechanisms.
AB  - Agents like retinoids, thyroid hormone, glucocorticoids, progesterone, androgens,
      which bind to members of the nuclear receptor superfamily, inhibit the synthesis
      of matrix metalloproteinases (MMPs) in many cell types. These Zn2(+)- and Ca2(+)
      dependent MMPs degrade components of the extracellular matrix (ECM), and precise
      regulation of their expression is crucial in many normal processes. However,
      inappropriate expression of MMPs contributes to a variety of invasive and erosive
      diseases, and inhibition of MMP synthesis provides an important mechanism for
      controlling such aberrant or dysregulated responses. Nuclear receptors control
      MMPs through a variety of seemingly redundant mechanisms. First, nuclear
      receptors act on the promoters of MMP genes to enhance or suppress trans
      activation. Ironically, in a family of genes that exhibits substantial regulation
      by nuclear receptors, few consensus hormone responsive elements (HREs) have been
      deomonstrated in MMP promoters. Rather, inhibition of MMPs occurs primarily, but
      not exclusively, at AP-1 sites. Here, nuclear receptors form complexes on the DNA
      through interactions with AP-1 proteins, sequester Fos/Jun and/or decrease the
      mRNAs for these transcription factors. Second, nuclear receptors and their
      ligands can indirectly inhibit MMPs. For instance, both retinoids and
      glucocorticoids induce the transcription of TIMPs (tissue inhibitor of
      metalloproteinases), which complex with MMPs and inhibit enzymatic activity, and
      progesterone stimulates production of transforming growth factor-beta (TGF-beta),
      which in turn suppresses MMP-7 (matrilysin). Finally, nuclear receptors bind to
      coactivators, corepressors, and components of the general transcriptional
      apparatus, but the potential role of these interactions in MMP regulation remains
      to be determined. We conclude that nuclear receptors utilize multiple, apparently
      redundant, mechanisms to inhibit MMP gene expression, assuring precise control of
      ECM degradation under a variety of physiologic and pathologic conditions.

PMID- 9196080
TI  - The HCFA proposal for changes in Medicare practice expenses: need for legislative
      action.

PMID- 9196079
TI  - RNA binding analysis of yeast REF2 and its two-hybrid interaction with a new gene
      product, FIR1.
AB  - The product of the REF2 gene is required for optimal levels of endonucleolytic
      cleavage at the 3' ends of yeast mRNA, prior to the addition of a poly(A) tail.
      To test the role of the previously demonstrated nonspecific affinity of REF2 for
      RNA in this process, we have identified RNA binding mutants in vitro and tested
      them for function within the cell. One REF2 variant, with an internal deletion of
      82 amino acids (269-350), displays a 10-fold reduction in RNA binding, yet still
      retains full levels of processing activity in vivo. Conversely, a series of
      carboxyl-terminal deletions that maintain full RNA binding capability have
      progressively decreasing activity. These results rule out a major role for the
      central RNA binding domain of REF2 in mRNA 3' end processing and demonstrate the
      importance of the carboxyl-terminal region. To ask if the stimulatory role of
      REF2 depends on interactions with other proteins, we used a two-hybrid screen to
      identify a new protein termed FIR1 (Factor Interacting with REF) encoded on
      chromosome V. FIR1 interacts with two independent regions of REF2, one of which
      (amino acids 268-345) overlaps the RNA binding domain and is dispensible for REF2
      function, whereas the other (amino acids 391-533) is located within the critical
      carboxyl-terminus. As with REF2, FIR1 has a small but detectable role in
      influencing the efficiency of poly(A) site use. Yeast strains containing a
      disrupted FIR1 gene are slightly less efficient in the use of cryptic poly(A)
      sites located within the lacZ portion of an ACT1-lacZ reporter construct.
      Likewise, a double delta ref2, delta fir1 mutant is more defective in processing
      of a reporter CYC1 poly(A) site than delta ref2 alone. This synergistic response
      provides additional support for the interaction of FIR1 with REF2 in vivo, and
      suggests that a number of gene products may be involved in regulating the
      cleavage reaction in yeast.

PMID- 9196078
TI  - Isolation and characterization of a dihydrofolate reductase gene mutation in
      methotrexate-resistant Drosophila cells.
AB  - Stepwise increases in methotrexate (MTX) concentration over a 4-year period led
      to the selection of a highly drug-resistant (2 x 10(-4) M MTX) Drosophila cell
      line. Uptake experiments with [3H]MTX showed a slightly lower level of
      intracellular MTX in the resistant S3Mtx cells than in the susceptible S3
      parental cell line. Southern blot analysis demonstrated that the gene for the MTX
      target, dihydrofolate reductase (DHFR), was not significantly amplified in the
      resistant line. To determine the molecular basis for resistance, the DHFR cDNA
      sequence was amplified by polymerase chain reaction from both the resistant and
      susceptible cells. Sequence comparison revealed a single T to A base change at
      nucleotide 89, which resulted in the substitution of Gln for Leu at residue 30 in
      S3Mtx cells. Expression and purification of the wild-type and mutant DHFR from E.
      coli cells showed that the S3Mtx enzyme had a reduced binding affinity for the
      antifolates, MTX and trimethoprim, with 15-fold higher K[d] and K[i] values than
      those from the wild-type enzyme. Molecular modeling confirmed that the
      replacement of the hydrophobic Leu by the more polar Gln was in the substrate
      binding site and thus would decrease the binding of MTX. These results suggest
      that the high level of MTX resistance in the selected cell line can be attributed
      to the mutation in the DHFR gene and also provides a model for pesticide
      resistance in insects.

PMID- 9196081
TI  - Anti-IgE therapy for asthma.

PMID- 9196083
TI  - Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early
      asthmatic response.
AB  - Inhaled allergens, acting through IgE-dependent mechanisms, are important
      triggers of asthma symptoms and inducers of airway hyperresponsiveness and airway
      inflammation. The effect of anti-IgE recombinant humanized monoclonal antibody
      E25 (rhuMAb-E25) on the provocation concentration of allergen causing a 15% fall
      in FEV1 (allergen PC15) during the allergen-induced early asthmatic response
      (EAR) was assessed in a multicenter, randomized, double-blind, parallel group
      study. Ten of 11 allergic asthmatic subjects randomized to receive intravenous
      rhuMAb-E25, 2 mg/kg on study day 0 and 1 mg/kg on Days 7, 14, 28, 42, 56, and 70
      completed the study; nine received intravenous placebo. The allergen PC15 was
      measured on Days -1, 27, 55, and 77 and methacholine PC20 on Days -2, 42, and 76.
      rhuMAb-25 was well tolerated and only one patient (active group) was withdrawn
      because of a generalized urticarial rash after the first dose. Compared with
      baseline values (Day -1), the median allergen PC15 on Days 27, 55, and 77 were
      increased by 2.3, 2.2, and 2.7 doubling doses (delta log PC15/0.3) respectively
      with rhuMAb-E25 and -0.3, +0.1, and -0.8 doubling doses with placebo (p < or =
      0.002). Methacholine PC20 improved slightly after rhuMAb-E25, this change
      becoming statistically significant on Day 76 (p < 0.05); no change was observed
      in the placebo group. Mean serum-free IgE fell by 89% after rhuMAb-E25 while
      there was no significant change after placebo. The inhibitory effects of rhuMAb
      E25 on allergen-induced EAR suggest that it may be an effective, novel
      antiallergic treatment for asthma.

PMID- 9196082
TI  - The effect of an anti-IgE monoclonal antibody on the early- and late-phase
      responses to allergen inhalation in asthmatic subjects.
AB  - A humanized murine monoclonal antibody directed to the Fc epsilonR1-binding
      domain of human IgE (rhuMAb-E25) has been shown to inhibit the binding of IgE to
      mast cells without provoking mast cell activation. To examine the effects of
      neutralizing IgE on allergic airway responses, we assessed the effects of 9 wk of
      treatment with rhuMAb-E25 in a parallel group, randomized, double-blind, placebo
      controlled study of 19 allergic asthmatic subjects. We found that treatment with
      rhuMAb-E25 reduced serum IgE, increased the dose of allergen needed to provoke an
      early asthmatic response, reduced the mean maximal fall in FEV1 during the early
      response (30 +/- 10% at baseline to 18.8 +/- 8%, versus 33 +/- 8% at baseline to
      34 +/- 4% after placebo; p = 0.01), and reduced the mean maximal fall in FEV1
      during the late response (24 +/- 20% at baseline to 9 +/- 10% versus 20 +/- 17%
      at baseline to 18 +/- 17% after placebo; p = 0.047). We conclude that an anti-IgE
      monoclonal antibody, which inhibits binding of IgE to its receptor, suppresses
      the early- and late-phase responses to inhaled allergen in allergic asthmatic
      subjects. Targeting IgE with rhuMAb-E25 might be a useful treatment for allergic
      asthma.

PMID- 9196084
TI  - Specific IgE-dependent sensitization, atopy, and bronchial hyperresponsiveness in
      apprentices starting exposure to protein-derived agents.
AB  - Atopy, specific IgE sensitization, and bronchial hyperresponsiveness (BHR) were
      examined in a cohort of 769 apprentices starting career programs in animal health
      or veterinary medicine (Group 1), pastry making (Group 2), and dental hygiene
      (Group 3). The hypothesis were that: (1) a proportion of subjects can be
      "sensitized" although no significant specific occupational exposure has occurred;
      and (2) there is a relationship between baseline specific sensitization to work
      related antigens and host characteristics. Skin tests were administered using 11
      common inhalants and specific allergens, including six laboratory animal
      extracts, three cereal antigens, alpha-amylase, and latex. Methacholine challenge
      tests were performed. The prevalence of atopy was 54.4% in Group 1, 58.1% in
      Group 2, and 52.5% in Group 3. Skin reactivity to work-specific proteins was as
      follows: laboratory animal proteins, 13.8% in Group 1, 14.0% in Group 2, and
      15.6% in Group 3. No subject was sensitized to alpha-amylase, whereas 1.2% in
      Group 1, 5% in Group 2, and 4.1% in Group 3 were sensitized to flour. Five
      subjects reacted to latex. BHR (PC20 < or = 8 mg/ml) was present in 17.6%, 21.2%,
      and 14.8% of subjects in Groups 1, 2, and 3, respectively. Specific sensitization
      was associated with positive skin reactions to common allergens, work-related
      symptoms, and BHR. These results suggest that students starting career programs
      with exposure to high-molecular-weight allergens have a low but substantial
      frequency of specific sensitization to work-related allergens that is related to
      atopy and BHR.

PMID- 9196085
TI  - Inhibition of antigen-induced acute bronchoconstriction, airway
      hyperresponsiveness, and mast cell degranulation by a nonanticoagulant heparin:
      comparison with a low molecular weight heparin.
AB  - Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti
      IgE-mediated mast-cell degranulation. We hypothesized that the antiallergic
      action of heparin may be dependent on molecular weight and related to its
      nonanticoagulant properties. Therefore, in the present investigation we studied
      the effects of a nonanticoagulant fraction of heparin (LA-heparin) on antigen
      induced bronchoconstriction, airway hyperresponsiveness (AHR), and mast-cell
      degranulation, and compared its antiallergic activity with that of a low
      molecular weight heparin (LMW-heparin, fragmin). Specific lung resistance (SRL)
      was measured in 15 sheep before, immediately after, and serially for as long as 2
      h after airway challenge with Ascaris suum antigen, without and after
      pretreatment with inhaled fractionated heparins at doses of 2.5 and 5 mg/kg.
      Airway responsiveness was estimated before, and 2 h after antigen as the
      cumulative provocating dose (PD400) of carbachol in breath units, which increased
      SRL by 400% (one breath unit was defined as one breath of 1% carbachol solution).
      LA-heparin caused a dose-dependent inhibition of antigen-induced
      bronchoconstriction, and a 5-mg/kg nebulized dose caused a 67% inhibition of
      allergic bronchoconstriction, whereas a 2.5-mg/kg dose was ineffective (20%
      inhibition). Inhaled fragmin was more potent than LA-heparin, as shown by 84%
      (2.5 mg/kg) and 82% (5 mg/kg) inhibition of allergic bronchoconstriction. Fragmin
      (5 mg/kg) also attenuated the postantigen AHR, whereas LA-heparin was
      ineffective. In vitro, preincubation with both LA-heparin and fragmin inhibited
      the anti-IgE-induced degranulation of rat peritoneal mast-cells in a dose
      dependent fashion. LA-heparin was fourfold more potent than fragmin, with IC50 of
      80 and 320 microg/ml, respectively. These data suggest that: (1) fractionated
      heparins attenuate antigen-induced acute bronchoconstriction, (2)
      nonanticoagulant fractions mediate the antiallergic activity of inhaled heparin,
      and (3) antiallergic activity of nonanticoagulant heparin and LMW-heparin may be
      related to prevention of mast-cell degranulation.

PMID- 9196086
TI  - Combined antagonism of leukotrienes and histamine produces predominant inhibition
      of allergen-induced early and late phase airway obstruction in asthmatics.
AB  - We defined the contribution of histamine and leukotrienes to allergen-induced
      airway obstruction in asthmatics; 12 subjects with allergic asthma underwent
      identical allergen bronchoprovocations on four occasions. At a control session,
      all subjects displayed early (EAR) and late asthmatic (LAR) reactions. The mean
      (+/- SE) drop in FEV1 during EAR (0-2 h) and LAR (2-12 h) was 29 +/- 2% and 28 +/
      4%, respectively. Thereafter, the influence of 1 wk randomized pretreatment with
      the leukotriene receptor antagonist zafirlukast (Accolate) (80 mg twice daily),
      the antihistamine loratadine (10 mg twice daily), and the combination of both
      antagonists was assessed. Expressed as AUC FEV1 in percent of the control
      reaction, zafirlukast reduced the response during EAR and LAR by 62 +/- 11% and
      55 +/- 12%, respectively (p < 0.05 versus control). Loratadine inhibited EAR and
      LAR by 25 +/- 14% and 40 +/- 16%, respectively (p < 0.05 versus control).
      Zafirlukast was significantly more effective than loratadine during EAR but not
      during LAR. The combination of zafirlukast and loratadine reduced the AUC FEV1
      during EAR and LAR further, by 75 +/- 8% and 74 +/- 14%, respectively (p < 0.05
      versus control). The combination was significantly (p < 0.05) more effective than
      either drug alone during the LAR. The findings indicate that leukotrienes and
      histamine together mediate the major part of both the EAR and the LAR following
      exposure of asthmatics to allergen. Combination of leukotriene antagonism and
      antihistamines may represent a new strategy for treatment of airway obstruction
      in asthma.

PMID- 9196087
TI  - Effect of short-term treatment with low-dose inhaled fluticasone propionate on
      airway inflammation and remodeling in mild asthma: a placebo-controlled study.
AB  - In a double-blind, parallel-group study, we examined the effect of short-term
      treatment with inhaled fluticasone propionate (FP) in a group of 20 nonsmoking
      asthmatic patients who required only beta2-agonists to control their symptoms. We
      administered FP (250 microg twice daily) or matched placebo for 6 wk.
      Methacholine challenge was performed before treatment, after 3 wk, and at the end
      of treatment. Each patient underwent bronchoscopy with bronchoalveolar lavage
      (BAL) and bronchial biopsy before and after treatment. Eight patients in the
      placebo group and nine patients in the FP group completed the study. Bronchial
      responsiveness to methacholine decreased significantly only after 6 wk of
      treatment with FP (p < 0.05). When we compared the FP group with the placebo
      group, we observed a significant decrease only in the number of cells expressing
      intracellular adhesion molecule-1 (ICAM-1) and MAC-1 (p < 0.04 and p < 0.03,
      respectively). Moreover, we saw that the tryptase level in BAL decreased (p <
      0.001), whereas the eosinophil cationic protein (ECP) level did not change
      significantly. Additionally, the number of eosinophils and mast cells in the
      lamina propria in bronchial biopsies specimens was significantly smaller in the
      FP group than in the placebo group (p < 0.02 and p < 0.01, respectively).
      Additionally, in the FP group, we found that basement-membrane thickness was
      significantly decreased when compared with that of the placebo group (p < 0.05).
      In conclusion, our results show that short-term treatment with low-dose FP
      reduces inflammatory cell infiltration into the lamina propria in bronchial
      biopsy specimens. Moreover, short-term low-dose FP treatment might control the
      intensity of airway remodeling in mild asthma.

PMID- 9196088
TI  - Rhinovirus infection preferentially increases lower airway responsiveness in
      allergic subjects.
AB  - Rhinovirus (RV) infections are important triggers of acute asthma symptoms in
      susceptible persons. To determine whether the presence of allergy is a risk
      factor for enhanced lower airway effects during RV infection, we experimentally
      infected (RV16) 18 volunteers with allergic rhinitis and 13 normal control
      subjects and measured the effects on the response of the lower airways to
      histamine. All subjects were successfully infected, as indicated by increased
      upper respiratory symptoms and RV16 cultured from nasal secretions. The change in
      histamine PD20(deltaPD20) caused by RV infection was significantly different in
      allergic subjects from that in nonallergic control subjects (deltaPD20 = -0.40
      versus -0.03 log units, p = 0.04). This relationship was strengthened after
      adjusting for initial PD20 and FEV1 (mean deltaPD20 = -0.43 versus 0.01 log
      units, p < 0.01). The virus-induced deltaPD20 was also influenced by baseline
      lung function: there was a positive correlation between initial FEV1 and
      deltaPD20, and a weak but significant negative correlation between baseline PD20
      and deltaPD20. These findings indicate that host factors such as allergy,
      baseline FEV1, and baseline PD20 influence the changes in lower airway physiology
      caused by RV infection and raise the possibility that these factors contribute to
      the increased lower airway effects of RV infection in subjects with asthma.

PMID- 9196089
TI  - Free and complexed interleukin-8 in blood and bronchial mucosa in asthma.
AB  - We have tested the hypothesis that the expression of interleukin-8 (IL-8) is
      increased in bronchial tissue and circulating leukocytes of atopic asthmatics,
      indicating a role for this chemokine in asthma. The concentration of IL-8 in its
      free form and complexed with IgG or IgA was measured by ELISA in bronchial
      tissue, serum, and lysates of freshly isolated peripheral blood mononuclear cells
      and granulocytes from subjects with mild or severe asthma and nonatopic
      nonasthmatic subjects. Serum ECP was measured by fluorescent enzyme immunoassay.
      Free IL-8 was detected in the sera (n = 44) and bronchial tissue (n = 9) of all
      subjects with severe atopic asthma, but it was undetectable in normal subjects
      and subjects with mild atopic asthma, suggesting that free IL-8 is a marker of
      severe asthma. A positive correlation between free IL-8 and serum ECP levels
      found in severe disease suggests that IL-8 is associated with eosinophil
      activation. Complexes of IL-8 with IgA and IgG were detected in all serum and
      tissue samples. However, the levels of the IL-8-IgA complex were increased in the
      bronchial mucosa in asthma, and in blood were related to disease activity.
      Together, these results point to upregulation of IL-8 production in asthma and
      the induction of IL-8 binding immunoglobulins of the IgA class in the inflamed
      mucosa. We suggest a proinflammatory role for these complexes in lung tissue.

PMID- 9196090
TI  - Modulation of endothelin production and metabolism in guinea-pig tracheal
      epithelial cells by peptidase inhibitors.
AB  - Endothelins (ET-1, ET-2, ET-3) are potent bronchoconstrictors and growth
      promoting mediators. They are released from various cells such as endothelial and
      epithelial cells. In the airways, ETs are released under basal and stimulated
      conditions. In patients with status asthmaticus and other pulmonary disorders,
      the expression and production of ET-1 are increased. We investigated the
      activities of endothelin-converting enzymes (ECE) and endothelin-degrading
      enzymes, mostly neutral endopeptidases (NEP), in guinea-pig tracheal epithelial
      cells in culture through the use of various enzyme inhibitors. We found that
      among ETs, only ET-1 was steadily released under basal conditions over 24 h. The
      basal production was attenuated by both phosphoramidon and CGS 26 303, dual NEP
      and ECE inhibitors. Conversely, thiorphan, a selective NEP inhibitor, did not
      attenuate but rather increased the concentration of ET-1 in cell supernatants.
      CGS 24 592 and SQ 28 603, other NEP inhibitors, also increased the concentrations
      of ET-1 in cell supernatants in a concentration-dependent manner. However, at a
      high concentration, SQ 28 603 also inhibited the basal release of ET-1, which
      would suggest a non-selective inhibitory activity against ECE. These data suggest
      that ET-1 is simultaneously produced and degraded by guinea-pig tracheal
      epithelial cells via phosphoramidon-sensitive ECE and NEP pathways, respectively.
      This observation is of interest when considering that asthmatic patients were
      shown to have a damaged airway epithelium combined with the loss of NEP activity,
      which was associated with an increased expression and production of ET-1.

PMID- 9196091
TI  - Endothelin receptor antagonists inhibit antigen-induced lung inflammation in
      mice.
AB  - In this study, we have examined the effect of endothelin (ET) receptor
      antagonists on lung granulocyte inflammation after antigen challenge in
      sensitized mice. The antagonists used were BQ-123, an ETA antagonist, BQ-788, an
      ETB antagonist, and SB209670, an ET(A&B) antagonist. Thirty minutes prior
      exposure to aerosolized ovalbumin, ET antagonists (50 pmol/mouse) were
      administered directly into the lungs of sensitized Balb/c mice via the intranasal
      route. BQ-123 and SB209670 significantly decreased eosinophil number in the
      bronchoalveolar lavage fluid by 47 and 68%, respectively. Both compounds also
      inhibited neutrophil infiltration into the lungs. In contrast, BQ-788 did not
      affect granulocyte infiltration. A similar inhibition of lung eosinophilia was
      also obtained with an anti-ET antibody applied via the intranasal route. BQ-123
      and SB209670, but not BQ-788, significantly increased the production of
      interferon-gamma (Th1 cytokine) from purified lung Thy1.2+ cells without
      affecting interleukin-4 and interleukin-5 (Th2 cytokines) secretion. Furthermore,
      neutralizing antibody against interferon-gamma prevented the inhibitory effect of
      the ETA antagonist. Taken together, these results suggest an important
      pathophysiologic role for ET in the development of lung inflammation in asthma
      and highlight the potential of ET antagonists for the treatment of the disease.

PMID- 9196093
TI  - Sensitization to Aspergillus fumigatus and lung function in children with cystic
      fibrosis.
AB  - Colonization with Aspergillus fumigatus (Af) constitutes a common finding in
      children with cystic fibrosis (CF). The relationship between sensitization to Af
      and lung functon (LF) was studied in 118 patients with CF (61 girls and 57 boys;
      mean age: 14.3 yr; SD: 7 yr). Mean follow up was 2.2 yr. On average, 8.1 (SD:
      4.8) LF tests were performed per patient. Measurement of total IgE and specific
      IgE antibodies to Af, and a skin prick test (SPT) for Af, were done once a year.
      Thirty-one children (26%) were sensitized to Af. On average, LF parameters were
      not significantly different in Af-sensitized children than in nonsensitized
      children. Linear regression analyses were performed, using the repeated measures
      design. With adjustment for gender, age, height, and weight, sensitization to Af
      was associated with lower values of FEV1 (beta = -0.209; p < 0.05) and FEF(25-75)
      (beta = -0.356; p < 0.01). Analysis of different subgroups of sensitization
      demonstrated the effect on LF only in Af-sensitized patients with elevated total
      IgE levels, and not in Af-sensitized patients with normal IgE levels.
      Furthermore, there was evidence for a more rapid decline in LF for Af-sensitized
      patients with elevated total IgE levels than in those with normal IgE levels. We
      conclude that sensitization to Af in the presence of increased IgE values is
      associated with lower LF values in children with CF.

PMID- 9196092
TI  - Asthma in a Vietnamese refugee population.
AB  - Asians and Pacific Islanders comprise a large and growing minority group in the
      United States, yet data on health status specific to these populations are scant.
      We conducted an epidemiologic study of asthma in a Vietnamese refugee population
      to estimate prevalence, evaluate risk factors, and better understand treatments
      of asthma among Vietnamese individuals. One hundred twenty-four asthma cases were
      identified from a population of 2,536 new Vietnamese refugees in San Diego
      (prevalence = 49 per 1,000; 4.9%). Two nonasthmatic control groups of Vietnamese
      refugees, matched for age and gender with the asthma cases, were recruited for a
      case-control study, using a questionnaire administered in Vietnamese. Vietnamese
      asthmatic individuals used both Western and non-Western therapies. Most subjects
      used traditional health practices, such as coining, cupping, and oil inhalation.
      As compared with current-refugee controls, the asthmatic subjects used
      significantly more bleeding (OR: 3.40; 95% CI: 1.06 to 10.80) and herbal
      ingestion (OR: 1.87; 95% CI: 1.08 to 3.19). As compared with former-refugee
      controls, the asthmatic subjects used significantly more oil inhalation (OR:
      2.58; 95% CI: 1.45 to 4.85), bleeding (OR: 8.64, 95% CI: 1.02 to 73.70), and
      herbal ingestion (OR: 1.93; 95% CI: 1.02 to 3.67). The presentation and
      recognition of asthma among the Vietnamese subjects were similar to those in
      other populations. This information may be helpful in designing culture-specific
      health-education programs.

PMID- 9196094
TI  - Conventional and modified nasal potential-difference measurement in cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is associated with impaired ion transport across epithelial
      membranes and an increased transepithelial potential difference (PD) that can be
      measured in airway epithelium. The aim of this study was to investigate the
      diagnostic value of nasal PD in CF, and to test a modified approach to the
      measurement of this PD. The reproducibility and diagnostic sensitivity and
      specificity of nasal PD measurements were tested with the perfusion technique and
      with a simplified modification of the technique done with a novel, solid-state
      exploring electrode. With the perfusion method, basal PD values were different in
      CF patients (mean +/- SEM: -51.6 +/- 0.9 mV, n = 104) than in normal (-15.5 +/-
      0.9 mV, n = 58, p < 0.01) subjects. CF patients with acute rhinitis or other
      nasal pathology had mean PD values that were intermediate between those of the
      patients and normal and disease-control groups (-28.3 +/- 1.2 mV, n = 40, p <
      0.01, different from normal). The diagnostic sensitivity of the perfusion method
      for CF was 91.3%, and the specificity was 96.4%. PD measurements with the
      modified technique correlated highly with the results achieved with the perfusion
      method (r = 0.94, n +/- 158). The measurement of nasal PD effectively
      distinguishes CF from control subjects. Care must be taken in the interpretation
      of measurements made on acutely inflamed epithelium. The modified method was
      simpler than the conventional perfusion technique, and equally effective.

PMID- 9196095
TI  - A cystic fibrosis transmembrane conductance regulator splice variant with partial
      penetrance associated with variable cystic fibrosis presentations.
AB  - Some patients express various features of cystic fibrosis (CF) even though
      essential characteristics of the disease might be absent. Such patients may
      suffer from respiratory disease without pancreatic insufficiency and normal sweat
      chloride levels. Others may present as male infertility because of congenital
      bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T
      allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene that reduces the level of the normal CFTR
      transcripts, was found in increased frequency among male patients with CBAVD. The
      purpose of this study was to investigate the possibility that the 5T allele is
      associated with dysfunction of organs other than the male reproductive system,
      leading to CF or atypical CF. Analysis of the 5T allele was performed on 148
      subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232
      chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from
      healthy subjects of Ashkenazi origin. The frequency of the 5T allele among
      chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six
      of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi
      population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of
      the five patients with CF and the 12 patients with atypical CF carrying the 5T
      allele indicated that most patients suffered from respiratory disease presenting
      as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis,
      or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium
      ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients
      with respiratory disease who were old enough to be evaluated for fertility
      status, five were fertile and one had pancreatic insufficiency. Among male
      patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele
      is a variant with partial penetrance causing disease with an extreme variability
      of clinical presentation: from normal healthy fertile subjects or male patients
      with CBAVD to those with atypical or typical clinical phenotype of CF.

PMID- 9196096
TI  - Absence of health insurance is associated with decreased life expectancy in
      patients with cystic fibrosis.
AB  - Life expectancy for individuals with cystic fibrosis (CF) has increased
      dramatically in the last 30 yr, but it is unclear whether the improved survival
      has applied equally to individuals with different health insurance status. We
      developed a retrospective inception cohort of all 189 patients with CF born
      1/1/55 to 12/31/70 who had at least one hospitalization at a university referral
      center. The median survival for patients with CF who were without health
      insurance was 6.1 yr compared with 20.5 yr for those with Medicaid and 20.5 yr
      for those with private insurance. Using multivariate Cox regression, health
      insurance and increased socioeconomic status were independently associated with
      longer survival. The adjusted relative risk of death was greater for the absence
      of health insurance than for factors previously shown to predict mortality in
      individuals with CF (female sex and presentation with meconium ileus). In
      summary, the absence of health insurance was associated with increased mortality
      rate in children with CF and was a stronger predictor of mortality than variables
      previously shown to be associated with mortality for CF. If increasing numbers of
      children with CF lose health insurance coverage, our results suggest that their
      life expectancy will decrease dramatically.

PMID- 9196097
TI  - Exercise ability in survivors of severe bronchopulmonary dysplasia.
AB  - There is limited information concerning the exercise performance of long-term
      survivors of bronchopulmonary dysplasia (BPD), and much of what is available
      pertains to those with relatively mild disease. The present study was undertaken
      to describe exercise responses in patients with a history of severe BPD, defined
      as those patients with a clinical and radiographic diagnosis of BPD who required
      supplemental oxygen at least until they were 44 wk postconceptual age and who
      were discharged home on oxygen. Fifteen children with a history of severe BPD
      were matched for gestational age with 15 children who had previously had
      respiratory distress syndrome but who did not develop BPD (Prem). These Prem
      control children were subsequently compared with 13 healthy control children born
      at term (Control) who were of similar postnatal age. Participants underwent
      pulmonary function testing, progressive exercise testing on a cycle ergometer,
      and a steady-state exercise test with cardiac output determined by CO2
      rebreathing. Despite the patients with BPD having a lower FEV1 than those in the
      Prem group, who had lower values than the Control group (BPD, 64 +/- 21%; Prem,
      85 +/- 11%; Control, 95 +/- 8%), the exercise capacity did not differ between the
      BPD and the Prem and between the Prem and the Control groups (BPD, 84 +/- 15%;
      Prem, 81 +/- 17%; Control, 91 +/- 12%). However, the BPD patients used a greater
      percentage of their ventilatory reserve (VEmax/40 FEV1: BPD, 93 +/- 20%; Prem, 67
      +/- 12%; Control, 59 +/- 13%). Of the four patients with BPD who had significant
      oxygen desaturation with exercise, three had the lowest values for FEV1. Cardiac
      output was appropriate for oxygen consumption in most patients.

PMID- 9196098
TI  - Comparison of indirect calorimetry and thermodilution cardiac output measurement
      in children.
AB  - We validated experimentally the ability of hood indirect calorimetry to measure
      accurately VO2. For this purpose we compared cardiac output calculated from the
      Fick equation Q = VO2/(Ca(O2) - CV(O2)), in which VO2 was obtained by hood
      indirect calorimetry, to thermodilution cardiac output (Qth) measured
      simultaneously during cardiac catheterization in children (n = 16). Because
      FI(CO2) is a critical factor in hood indirect calorimetry calculations, we also
      assessed the consequence of taking into account measured FI(CO2) rather than
      using the usual standard value of 0.0004. We found a good agreement between Q and
      Qth whether we used experimentally measured FI(CO2) in ambient air (Qth = 0.89 Q
      + 0.39, r = 0.941) or standard FI(CO2) (Qth = 0.84 Q + 0.55, r = 0.930). However,
      VCO2 and R computed from standard FI(CO2) differed significantly (p < 0.001) from
      values derived from measured FI(CO2). This demonstrates that indirect calorimetry
      allows reasonable estimates of Q, VO2, VCO2, and R provided that the actual
      values of FI(CO2) are used.

PMID- 9196099
TI  - Airway hyperresponsiveness and cough-receptor sensitivity in children with
      recurrent cough.
AB  - In children, recurrent cough is a common presenting symptom that may represent
      asthma. We tested the hypotheses that children with recurrent cough have
      increased cough-receptor sensitivity (CRS) or airway hyperresponsiveness (AHR).
      Skin prick testing, the capsaicin CRS test, and hypertonic saline (HS) challenge
      were performed in 44 children (median age: 8.9 yr) with recurrent dry cough (> or
      = 2 episodes of cough, each lasting > or = 2 wk, within a period of 12 mo) and 44
      controls. Measures of CRS were the concentration of capsaicin required to
      stimulate > or = 2 coughs (Cth) and > or = 5 coughs (C5). During the coughing
      period, Cth (mean log: 0.62 [95% CI: 0.43 to 0.81]) and C5 (mean log: 1.15 [95%
      CI: 0.86 to 1.44]) of the subjects without AHR were significantly lower (p =
      0.0026, 0.027, respectively) than Cth (mean log: 1.27 [95% CI: 0.88 to 1.66]) and
      C5 (mean log: 1.79 [95% CI: 1.21 to 2.37]) of the subjects with AHR and those of
      the controls (p = 0.0002 and 0.0001). During the cough-free period, there was no
      difference in CRS among the groups. In subjects who demonstrated AHR, the
      provocation dose causing a > or = 15% fall in FEV1 (PD15) during the cough period
      was significantly lower (p = 0.005) than that during the cough-free period. We
      conclude that AHR or increased CRS is present during the coughing phase in
      children with recurrent cough.

PMID- 9196100
TI  - Comparison of assisted ventilator modes on triggering, patient effort, and
      dyspnea.
AB  - In 11 ventilator-dependent patients, we undertook a head-to-head comparison of
      patient-ventilator interaction during four ventilator modes: assist-control
      ventilation (ACV), intermittent mandatory ventilation (IMV), pressure support
      (PS), and a combination of IMV and PS. Progressive increases in IMV rate and PS
      level each decreased inspiratory pressure-time product (PTP) (p < 0.0001). These
      reductions in PTP were greater with PS than with IMV at lower but proportional
      levels of maximal assistance (p < 0.005). When PS 10 cm H2O was added to a given
      level of IMV, greater reductions in PTP were achieved not only during intervening
      (PS) breaths (p < 0.001), but also during mandatory (volume-assisted) breaths (p
      < 0.0005); this additional unloading during mandatory breaths was proportional to
      the decrease in respiratory drive (dP/dt) during intervening breaths (r = 0.67, p
      < 0.0001). Maximal unloading occurred with ACV, achieving more than a fivefold
      decrease in PTP compared with unassisted breathing. Decreases in PTP were
      confined to the post-trigger phase, and PTP of the post-trigger phase correlated
      with dP/dt (r = 0.78, p < 0.0001). Effort during the trigger phase remained
      constant despite marked changes in drive and intrinsic positive end-expiratory
      pressure (PEEPi). Ineffective triggering occurred with all modes, and wasted PTP
      increased with increasing levels of assistance as a result of the accompanying
      decrease in drive and increase in volume. Breaths preceding nontriggering efforts
      had shorter respiratory cycle times (p < 0.0005) and expiratory times (p <
      0.0001) and higher PEEPi (p < 0.0001), indicating that neural-mechanical
      asynchrony resulted from inspiratory activity commencing prematurely before
      elastic recoil pressure had fallen to a level that could be overcome by a
      patient's muscular effort. Thus, increases in the level of ventilator assistance
      produced progressive decreases in inspiratory muscle effort and dyspnea,which
      were accompanied by increases in the rate of ineffective triggering.

PMID- 9196101
TI  - Small airway closure and positive end-expiratory pressure in mechanically
      ventilated patients with chronic obstructive pulmonary disease.
AB  - The effects of positive end-expiratory pressure (PEEP) on alveolar recruitment
      and closing volume were studied in ten supine, sedated, and paralyzed patients
      with chronic obstructive respiratory disease and acute respiratory failure. We
      applied PEEP (0, 5, 10, and 15 cm H2O) and constructed inflation static volume
      pressure (V-P) curves. In all patients, the static V-P curves obtained at
      different PEEP levels were superimposed on each other, indicating that with PEEP
      there was no recruitment of previously atelectatic lung units. However, the
      static V-P curves exhibited an inflection point, which should reflect the
      critical pressure (Po) required to reopen all closed airways, whilst the
      corresponding lung volume (Vo) reflects the opening volume. On average, Vo was
      0.71 L above the relaxation volume of the respiratory system (Vr). All patients,
      however, exhibited dynamic hyperinflation, i.e., with zero PEEP (ZEEP) the end
      expiratory lung volume (EELV) was 0.54 L above Vr. Nevertheless, in seven
      patients the EELV on ZEEP was below Vo, resulting in cyclic reopening and closure
      of small airways with each breathing cycle, with concomitant mechanical stresses
      on the peripheral airways that may lead to low-volume barotrauma. Such barotrauma
      may be prevented by increasing with PEEP the EELV to Vo.

PMID- 9196102
TI  - Effects of inhaled nitric oxide or inhibition of endogenous nitric oxide
      formation on hyperoxic lung injury.
AB  - Nitric oxide (NO) may either protect against or contribute to oxidant-induced
      lung injury. In this study, we sought to determine whether either inhaled NO in
      concentration of 10 and 100 parts per million (ppm) or inhibition of endogenous
      NO formation with L-NG nitroarginine methyl ester (L-NAME) or aminoguanidine
      alters the extent of lung injury in rats breathing 100% O2. Lung thiobarbituric
      acid reactive substances (TBARS), wet to dry lung weight ratio (Q(W)/Q(D)),
      vascular and epithelial permeability (assessed by simultaneous intravenous
      administration of 131I-labeled albumin and intraalveolar instillation of 125I
      labeled albumin), alveolar liquid clearance (evaluated based on the increase in
      alveolar protein concentration), and lung liquid clearance (gravimetric method)
      were determined after 40 h exposure to either 100% or 21% O2. Exposure to
      hyperoxia caused increases in lung TBARS from 10.5 +/- 0.7 to 13.7 +/- 1.5
      micromol/mg protein (p < 0.05); in blood hemoglobin concentration (Hb) from 14 +/
      1 g/dl to 17 +/- 1 g/dl (p < 0.05); in the Q(W)/Q(D) ratio from 4.02 +/- 0.3 to
      5.31 +/- 0.5 (p < 0.05); and in alveolar-arterial oxygen tension difference from
      124 +/- 14 mm Hg to 241 +/- 61 mm Hg (p < 0.05); as well as a decrease in blood
      pressure, from 131 +/- 15 mm Hg to 72 +/- 26 mm Hg (p < 0.05). Hyperoxia also
      increased vascular albumin leakage and moderately altered epithelial barrier
      permeability to protein. Inhalation of 10 ppm NO prevented the increases in TBARS
      and Q(W)/Q(D), had no effect on the alveolar barrier impermeability to protein,
      and improved alveolar liquid clearance. Inhalation of 100 ppm NO did not alter
      the increases in TBARS and Q(W)/Q(D) but increased vascular permeability to
      protein. Survival of rats exposed to hyperoxia was not improved by inhaled NO.
      Treatment with L-NAME or aminoguanidine reduced survival. L-NAME, but not
      aminoguanidine, increased lung TBARs. These results suggest that, depending on
      its concentration, inhaled NO can either reduce or increase the early
      consequences of hyperoxic lung injury. Treatment with L-NAME, and to a lesser
      extent aminoguanidine, worsened hyperoxic lung injury, indicating a protective
      effect of endogenous NO.

PMID- 9196104
TI  - TNF mediates lung leak, but not neutrophil accumulation, in lungs of rats given
      IL-1 intratracheally.
AB  - Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with
      acute respiratory distress syndrome, and administering IL-1 intratracheally to
      rats causes an acute, neutrophil-dependent, oxidative lung leak. We found that
      rats given IL-1 intratracheally had increased lung lavage fluid tumor necrosis
      factor (TNF) levels, and that rats treated with TNF binding protein (TNFbp)
      intravenously did not develop the increased lung leak that occurs after
      administration of IL-1 intratracheally. In contrast, rats given IL-1
      intratracheally and TNFbp intravenously had the same elevations in lung lavage
      neutrophil accumulation and lung lavage cytokine-induced neutrophil
      chemoattractant levels as rats given IL-1 intratracheally. Our results show that
      TNFbp decreases neutrophil-mediated lung leak, but not lung neutrophil
      accumulation, after administration of IL-1 intratracheally in rats.

PMID- 9196103
TI  - Effects of norepinephrine on regional blood flow and oxygen extraction
      capabilities during endotoxic shock.
AB  - We explored the effects of norepinephrine on blood flow distribution and oxygen
      extraction capabilities during hyperdynamic endotoxic shock. Twelve anesthetized
      and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin
      followed by a general saline infusion and were then randomly divided into two
      groups: six received norepinephrine (1 microg/kg/min), and six served as control
      subjects. The norepinephrine group maintained higher mean arterial pressure,
      cardiac index, left ventricular stroke work index, and hepatic arterial blood
      flow without altering blood flow to portal, mesenteric, and renal beds. When
      cardiac tamponade was induced to study tissue oxygen extraction capabilities, the
      norepinephrine group had a lower critical oxygen delivery in whole body (11.5 +/-
      5.2 versus 14.3 +/- 1.4 ml/kg/min, p < 0.05) and in liver (25.0 +/- 11.3 versus
      38.0 +/- 9.0 ml/min, p = NS) and a higher critical oxygen extraction ratio in
      whole body (53.8 +/- 17.7 versus 32.0 +/- 6.1%, p < 0.05), and in liver (57.0 +/-
      11.9 versus 35.2 +/- 4.3%, p < 0.05). We conclude that during endotoxic shock in
      dogs, norepinephrine hardly influences blood flow distribution and could even
      increase hepatic artery blood flow, and it can also improve whole body and liver
      oxygen extraction capabilities.

PMID- 9196105
TI  - Leukocytes and decreased left-ventricular contractility during endotoxemia in
      rabbits.
AB  - We hypothesized that leukocytes contribute to decreased myocardial contractility
      following endotoxin infusion. To test this hypothesis, we administered endotoxin
      (1 mg/kg intravenously) to intact, anesthetized rabbits whose arterial blood
      perfused two isolated hearts at a constant pressure (75 mm Hg). One heart was
      perfused with blood passed through a leukocyte filter, whereas the other received
      unfiltered blood. Contractility of both hearts was measured every 30 min for 6 h,
      using the slope of the end-systolic pressure-volume relationship (Emax) and the
      maximum rate of change of intraventricular pressure (dP/dt(max)). In the
      unfiltered hearts at 6 h, Emax decreased to 81 +/- 6% (mean +/- SEM) of baseline
      (p < 0.05). In the hearts perfused with leukocyte-filtered blood there was no
      change in Emax. Similarly, dP/dt(max) decreased 74 +/- 9% of baseline in the
      hearts receiving unfiltered blood (p < 0.05) but did not decrease in the hearts
      receiving leukocyte-filtered blood. The leukocyte filter significantly reduced
      the number of neutrophils in perfusing blood (p < 0.01), decreased the number of
      neutrophils in the heart by 77% (p < 0.01), and decreased myocardial morphometric
      changes (p < 0.05). A 55 +/- 18% reduction in neutrophil L-selectin expression
      after endotoxin infusion (p < 0.01) suggests that the neutrophils were
      significantly activated. We conclude that leukocytes, notably activated
      neutrophils, may contribute to decreased myocardial contractility during septic
      shock.

PMID- 9196106
TI  - Lung-volume reduction improves dyspnea, dynamic hyperinflation, and respiratory
      muscle function.
AB  - Lung-volume reduction surgery (LVRS) improves static lung elastic recoil in
      selected patients with severe chronic obstructive pulmonary disease (COPD). This
      explains the increase in FEV1 in many COPD patients who undergo LVRS, but fails
      to explain clinical improvement in those without changes in FEV1. We
      prospectively evaluated 17 patients after pulmonary rehabilitation but prior to
      and again at least 3 mo after bilateral LVRS done via median sternotomy. In
      addition to pulmonary function, lung elastic recoil, walking distance, and
      exercise capacity, we evaluated static and dynamic respiratory muscle (RM)
      function, and dyspnea. In 12 patients we also quantified dynamic hyperinflation
      (end-expiratory and end-inspiratory lung volume [EELV and EILV, respectively]).
      After LVRS, FEV1 rose from 26.7 +/- 1.8 to 39.0 +/- 3.7% predicted (p < 0.004),
      whereas TLC dropped from 134.7 +/- 4.8 to 118.3 +/- 4.4% predicted (p < 0.0002),
      and RV from 239.6 +/- 14.8 to 180.3 +/- 8.7% predicted (p < 0.0002). Isowork
      dyspnea decreased as assessed with a visual analogue scale (VAS) (79.6 +/- 5.2
      versus 49.3 +/- 7.5 mm, p < 0.005) and the Borg scale (7.1 +/- 0.6 versus 3.5 +/-
      0.6, p = 0.002). Walking distance improved significantly and, in the 12 patients
      in whom they were measured, EELV and EILV decreased at rest and at isowork.
      Maximal transdiaphragmatic pressure rose from 67.1 +/- 8.3 to 92.0 +/- 7.5 cm H2O
      (p < 0.03). Resting RM function changed little, but at isowork improved
      significantly after LVRS. Excluding one outlier, there was a strong linear
      correlation between the change in Borg-scale score at equivalent work loads
      before and after LVRS and the change in EELV (% predicted TLC, r = 0.75, p <
      0.001), as well as between the change in Borg-scale score and the absolute
      decrease in end-expiratory pleural pressure (Ppl(e)) (r = 0.78, p = 0.004).
      Successful LVRS improves not only lung recoil, but also respiratory muscle
      function, and reduces dynamic hyperinflation. These changes help explain the
      decreased dyspnea and improved exercise capacity seen after LVRS, and add to
      current understanding of the mechanisms by which this procedure may help selected
      patients with severe emphysema.

PMID- 9196107
TI  - Respiratory-related pharyngeal constrictor muscle activity in normal human
      adults.
AB  - Electromyographic activity of the superior, middle, and inferior pharyngeal
      constrictor (PC) muscles was examined in 10 normal adult humans during
      wakefulness and sleep. Wire electrodes were inserted close to the midline of the
      posterior pharyngeal wall at the level of the soft palate (superior PC), tip of
      the epiglottis (middle PC), and corniculate tubercle (inferior PC). In general,
      the three PC muscles exhibited similar patterns of activation. The PCs were
      activated during swallows, repetitive "pa" sounds, changes in head position, and
      the last portions of slow inspiratory and expiratory vital capacity maneuvers.
      Respiratory-related PC activity was infrequent during quiet breathing during
      wakefulness; variable and inconsistent phasic activation in expiration in one or
      more of the PCs was present in seven of the 10 subjects, particularly after a
      swallow. Progressive hyperoxic hypercapnia and progressive isocapnic hypoxia were
      associated with recruitment of phasic PC activity, which was predominantly
      expiratory; however, variable discharge patterns were observed within a given
      muscle and a given subject. When phasic PC activity was present, preactivation
      during late inspiration was frequently observed. PC activity was absent in NREM
      sleep and exhibited sporadic, nonrespiratory-related bursts of activity during
      REM sleep. Passively induced hypocapnic hyperventilation in NREM sleep was not
      associated with PC activation. The results indicate that the PCs have very
      similar patterns of activation and exhibit phasic expiratory activity during
      relatively high ventilatory output states in wakefulness.

PMID- 9196108
TI  - Effects of inspiratory muscle unloading on the response of respiratory motor
      output to CO2.
AB  - Inspiratory muscle output is downregulated when the mechanical load is reduced in
      awake humans. It is not known whether this is related to reduction in PCO2 or to
      removal of load-related neural responses. To address this issue, we did Read CO2
      rebreathing tests in 13 normal subjects with and without unloading and compared
      respiratory output at identical end-tidal PCO2 (PET(CO2)) levels. Unloading was
      carried out with proportional assist ventilation (flow assist = 2 cm H2O/L/s plus
      volume assist = 4 cm H2O/L, representing approximately 50% reduction of the
      normal resistance and elastance). Ventilatory output (n = 13), total pressure of
      respiratory muscles (Pmus, n = 8), and transdiaphragmatic pressure (Pdi, n = 5)
      were computed at different PET(CO2) levels. Pmus was computed from esophageal
      pressure (Pes) using the Campbell diagram, and Pdi was measured from the
      difference between gastric pressure and Pes. Unloading caused an increase in
      ventilation (VI) and tidal volume (VT) at all PET(CO2) levels with no significant
      effect on slope (VI/PET(CO2) or VT/PET(CO2)) or respiratory rate. At low PET(CO2)
      (50 mm Hg), Pdi and Pmus waveforms did not differ with and without unloading. At
      high PET(C02) (59 mm Hg), peak Pdi and Pmus decreased by only 18.8 +/- 8.3% and
      13.8 +/- 9.5%, respectively (NS, p > 0.05). Using a model that allows
      nonlinearity in the pressure-volume relation and for intrinsic muscle properties
      (force-length and force-velocity relations), we estimated the expected changes in
      mean VT and VI when the level of assist used in this study was applied in the
      absence of any change in neural output response to CO2. The predicted and
      observed changes in VT and VI were similar. We conclude that when chemical
      stimuli are rigorously controlled, unloading does not result in downregulation of
      respiratory muscle activation.

PMID- 9196109
TI  - Influence of preload and afterload on genioglossus muscle length in awake goats.
AB  - The genioglossus is an upper airway dilator muscle, the length of which is
      directly related to patency in the oropharyngeal region. We hypothesized that
      genioglossal length (Lgg) is dynamically influenced by the afterload exerted by
      negative upper airway pressure during inspiration and by the intrinsic length
      tension characteristics of the muscle (preload). Seven awake goats were
      chronically instrumented with electrodes for EMGgg and sonomicrometry for Lgg. We
      examined the Lgg-EMGgg relationship during hypercapnia and inspiratory resistive
      loading (18 cm H2O/L/s). The goats breathed through the upper airway (TC) or
      airflow was diverted through a tracheostomy (TO). We found that: (1) passive
      inspiratory lengthening was observed with negative upper airway pressure (UAP)
      but not when UAP = 0 (TO breathing), (2) Lgg shortening for a given EMGgg was
      significantly decreased with negative inspiratory UAP, and (3) phasic Lgg
      shortening per unit EMGgg was greatest when Lgg was near optimal length (Lo). We
      conclude that genioglossal length is substantially influenced by afterload
      exerted by negative UAP and that genioglossal active shortening may be limited if
      the muscle operates at a length significantly greater or less than the optimal
      length.

PMID- 9196110
TI  - Effect of clarithromycin on nasal mucus properties in healthy subjects and in
      patients with purulent rhinitis.
AB  - Erythromycin inhibits mucus glycoconjugate secretion from airway cells in vitro
      and may increase mucus clearance in patients with asthma or diffuse
      panbronchiolitis. Because mucus hypersecretion is common in purulent rhinitis, we
      questioned whether clarithromycin would change the properties of nasal mucus from
      subjects without sinus disease and from patients with acute purulent rhinitis.
      Nasal secretions were collected before and after nasal methacholine challenge
      from 10 adults without nasal symptoms and without methacholine from 10 patients
      with purulent rhinitis. After 2 wk of oral clarithromycin (500 mg twice daily),
      secretions were again collected from both groups. Secretions were analyzed for
      viscoelasticity, cohesion, hydration, and ciliary and airflow (sneeze)
      transportability. Compared with secretions from healthy subjects, rhinitis
      secretions had decreased wettability (contact angle on Teflon 100 degrees versus
      84.67 degrees; p = 0.001), increased cohesion (36.8 versus 24.3 mm; p = 0.003),
      decreased sneeze clearability (20.6 versus 32 mm; p = 0.04), and increased
      percent solids (4.61 versus 2.82%; p = 0.04). After clarithromycin, the rheology,
      hydration, cohesion, and transportability of the rhinitis secretions were similar
      to those of the postclarithromycin secretions from the healthy subjects.
      Secretion volume also decreased (500.1 versus 28.3 mg; p = 0.01), and mucociliary
      transportability increased by 30% (0.76 versus 0.99; p = 0.005). Although
      clarithromycin reduced mucus secretion in both rhinitis patients and normal
      subjects, it did not alter the secretory response to methacholine.

PMID- 9196111
TI  - Inhaled gentamicin reduces airway neutrophil activity and mucus secretion in
      bronchiectasis.
AB  - To investigate whether aerosolized gentamicin (GM) prevents myeloperoxidase (MPO)
      mediated airway injury and mucus hypersecretion, a short course of aerosol
      therapy (3 d) with GM 40 mg or 0.45% saline (saline) twice per day was conducted.
      Twenty-eight patients with bronchiectasis and mucus hypersecretion after adequate
      chest care and hydration were enrolled in a randomized, double-blind fashion. MPO
      levels in sputum collected on arising were determined by fluorometric assay at
      655 nm before and after treatment. The sputum MPO level significantly decreased
      in patients receiving aerosolized GM, from 0.22 +/- 0.04 to 0.14 +/- 0.04 U/g (n
      = 15), but not in patients with saline inhalation (0.23 +/- 0.03 to 0.17 +/- 0.02
      U/g; n = 11). The daily sputum amount significantly decreased from 94.6 +/- 21.6
      to 58.1 +/- 17.8 ml (n = 13, p < 0.01) in the GM group, whereas it increased from
      78.6 +/- 25.4 ml to 120.5 +/- 33.9 ml (n = 11, p < 0.05) in the saline group. The
      change in the amount of daily sputum was related to that in the sputum MPO level
      in the GM group (r = 0.61; p < 0.01). Inhalation of GM, but not saline,
      significantly (p < 0.05) increased the value of peak expiratory flow (PEF) from
      186.4 +/- 25.1 to 216.4 +/- 26.4 L/min and decreased the variability of PEF from
      24.6 +/- 5.1 to 6.1 +/- 2.3 %. The nocturnal desaturation and the 6-min walking
      distances were also significantly improved in the GM group (11.2 +/- 3.8 to 0.6
      +/- 0.5 min/h; 324.9 +/- 43.1 to 408.1 +/- 25.9 m; p < 0.05; respectively), but
      not in the saline group. Subjective improvements in the Borg scale and self
      sputum assessment were found in the GM group only. In conclusion, aerosolized GM
      is effective in improving airway hypersecretion and inflammation in patients with
      bronchiectasis.

PMID- 9196112
TI  - Pulmonary and systemic inflammatory responses in rabbits with gram-negative
      pneumonia.
AB  - The major goals of this study were to define the relationships between
      intrapulmonary and systemic inflammatory responses in animals with gram-negative
      pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to
      1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events
      in the lungs and systemic circulation for 24 h. The treatment protocols resulted
      in groups of animals that mimicked the stages of the septic inflammatory response
      in humans. Animals treated with low inocula had systemic changes consistent with
      systemic inflammatory response syndrome and cleared the bacteria and inflammatory
      products from the lungs. Animals treated with high inocula failed to clear
      bacteria from the lungs, had severe intrapulmonary inflammatory responses, and
      developed septic shock. Intrapulmonary leukocyte recruitment was directly related
      to the size of the bacterial inoculum, but lung protein accumulation was not.
      Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were
      detectable in lung lavage fluid at 4 h and declined by 24 h in animals that
      cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO
      increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP
      1 increased between 4 h and 24 h in the lungs of all of the animals as the
      histologic response evolved from neutrophilic to mononuclear cell predominance.
      Thus, the intensity of systemic inflammatory and physiologic responses to
      intrapulmonary gram-negative infection depends on the inoculum size and whether
      the bacteria are cleared from or proliferate in the lungs. The results provide
      experimental support for the recently proposed classification of septic responses
      in humans.

PMID- 9196113
TI  - Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium
      avium complex pulmonary disease.
AB  - Mycobacterium avium complex (MAC) pulmonary disease with nodules and
      bronchiectasis is increasing. But the usefulness of computed tomography (CT) and
      bronchoscopy for diagnosis and the significance of MAC isolation from respiratory
      secretions are still unclear. For a 4-yr period, we prospectively examined the
      role of bronchoscopy with bronchial washing and transbronchial lung biopsy in 26
      patients who had clusters of small nodules in the periphery of the lung
      associated with ectatic changes of the draining bronchi on the CT scan. None of
      them was infected with human immunodeficiency virus. Thirteen of the 26 patients
      (50%) had cultures positive for MAC, six in the sputum and 13 in the bronchial
      washing. Epithelioid granuloma was demonstrated in eight of 13 patients with
      culture-positive MAC and in two of 13 patients in whom MAC was culture-negative.
      Rapidly growing mycobacteria were cultured in the two patients. Seven of the
      eight biopsy-positive patients received treatment and responded by sputum
      conversion and/or radiographic improvement. We found that the CT finding was a
      useful clue to suspect MAC pulmonary disease and that the bronchial washing was
      more sensitive than the routine expectorated sputum for MAC isolation.
      Demonstration of granuloma in more than half of the MAC-positive patients would
      suggest that MAC may have invaded the lung tissue rather than colonized in the
      airways.

PMID- 9196114
TI  - Observer variation and relationship of computed tomography to severity of
      beryllium disease.
AB  - Although high resolution computed tomography (HRCT) is commonly used to assess
      interstitial lung disease (ILD), relatively little is known about interrater
      reliability and construct validity of HRCT-reported nodules, ground-glass
      opacity, or other typical findings. We determined the interobserver and
      intraobserver variability of HRCT findings and correlated HRCT abnormalities with
      physiologic measures in 57 patients with chronic beryllium disease (CBD).
      Reliability of HRCT scan measurements were assessed using weighted kappa (K(W))
      and intraclass correlation coefficients. We correlated HRCT with spirometry, body
      plethysmographic lung volumes, diffusing capacity for carbon monoxide (DL(CO)),
      maximal exercise testing with measurement of arterial blood gases, and
      bronchoalveolar lavage (BAL). Interobserver agreement for three of the HRCT
      abnormalities found in CBD was moderate: the K(W) for nodules, septal lines, and
      ground-glass attenuation were 0.53, 0.44, and 0.53, respectively. Agreement was
      poor for bronchial wall thickening (K(W) = 0.15). HRCT scores correlated
      significantly with DL(CO), gas exchange at rest and at maximal exercise, and lung
      volume. This study demonstrates that HRCT has good interrater reliability and
      correlates with indices of the severity of granulomatous lung diseases such as
      CBD.

PMID- 9196115
TI  - Rapid prediction of rifampin susceptibility of Mycobacterium tuberculosis.
AB  - We evaluated the relationship between rifampin (RIF) susceptiblility and amino
      acid substitution in rpoB gene of Mycobacterium tuberculosis and the usefulness
      of rpoB gene sequencing in the rapid prediction of RIF susceptibility of M.
      tuberculosis in clinical specimens. A total of 76 genetic alterations in the 69
      bp core region of rpoB gene were detected in 74 of 130 M. tuberculosis strains.
      Examination of the correlation between the minimum inhibitory concentrations
      (MICs) of RIF and amino acid substitutions in the 69 bp core region of rpoB gene
      revealed that all 43 strains containing amino acid substitution with Leu or Trp
      in codon 531 showed RIF-resistant phenotypes, with MICs > or = 64 microg/ml. In
      contrast, a variable level of RIF susceptibility was observed among strains
      containing amino acid substitutions in either codon 516 or codon 526. In the
      clinical study, we tested 26 sputum samples, two gastric lavages, and one
      synovial fluid sample obtained from patients with tuberculosis. The RIF
      susceptibility predicted by direct rpoB sequencing was satisfactorily compatible
      with the results of the RIF-susceptibility test and the MICs of RIF against
      isolated organisms. Our results suggest that rpoB gene sequencing is useful for
      the detection of M. tuberculosis in clinical samples as well as the rapid
      prediction of RIF susceptibility of these strains.

PMID- 9196116
TI  - Cellular association of antiproteases in lavages from ventilated preterm human
      neonates.
AB  - Lung antiprotease activity is routinely assayed in the supernatant of
      bronchoalveolar lavage fluid (BALF). In this study the cellular fraction of
      lavages was also analyzed. Functionally active acid-resistant inhibitors with
      molecular masses characteristic of the mucus proteinase inhibitor (MPI, 14 kDa)
      and elastase-specific inhibitor (ESI, 7 kDa) were demonstrated by gel
      chromatography. Immunocytochemical studies of cells obtained at various postnatal
      time points from lavages of 10 premature infants with chronic lung disease showed
      that the inhibitors were confined to neutrophils and macrophages. At each time
      point, about 70% and 21% of these cells, respectively, stained positively. The
      polyclonal antibodies usually used to detect MPI did not distinguish between MPI
      and ESI. Because of this cross reactivity, it was not possible to differentiate
      between MPI and ESI. Analysis with reverse transcriptase-polymerase chain
      reaction (RT-PCR) of cells from lavages and of nucleated cells isolated from the
      peripheral blood showed the production of ESI only, but not of MPI. Nevertheless,
      MPI can associate with neutrophils and macrophages, as was shown in binding
      studies with the recombinant protein. These data suggest that when assaying
      bronchoalveolar lavages (BALs) for these antiproteases in the supernatant only,
      the total pool of inhibitors may be underestimated.

PMID- 9196117
TI  - Scar collagen deposition in the airways of allografts of lung transplant
      recipients.
AB  - Collagen subtype deposition has not been studied in the airways of transplanted
      lungs. As part of rejection, a series of immunologic insults results in a
      remodeling of the allograft. In chronic rejection, changes in the airway leading
      to obliterative bronchiolitis syndrome (OBS) are particularly important. To
      better understand the mechanism of OBS occurring in chronic lung rejection, we
      investigated deposition of three fibrillar collagens (type I, III, V) in airway
      biopsies of lung allografts taken from 10 clinically well lung transplant
      recipients (wLTR) and eight lung transplant recipients (LTR) with OBS (OBLTR)
      using an immunoperoxidase method. Collagen III deposition and the ratio of
      collagen type III to type I were found to be significantly increased in OBLTR
      compared with wLTR (p < 0.05), and the latter correlated inversely with both
      FEF(25-75) (r = -0.69; p < 0.05) and FEV1 (r = 0.62; p = 0.05) in OBLTR. This
      suggests that an increased proportion of collagen III in the airway walls of
      transplanted lungs might be an early signal of the progression to terminal
      chronic lung allograft dysfunction. The changes in the ratio of type III to type
      I collagen in the airways of lung allografts may provide important insights into
      the process of airway remodeling in chronic lung rejection.

PMID- 9196118
TI  - Cytomegalovirus infection enhances experimental obliterative bronchiolitis in rat
      tracheal allografts.
AB  - Inbred DA (AG-B4, RT1a) and WF (AG-B2, RT1v) rat immunosuppressed with
      cyclosporine A (CsA) 2 mg/kg/day subcutaneously were used as donors and
      recipients of heterotopic rat tracheal allografts. Acute infection was
      established by inoculating the recipients with 10(5) plaque-forming units of rat
      cytomegalovirus (RCMV) intraperitoneal on the day of transplantation. Chronic
      RCMV infection was similarly established 8 wk before transplantation in donors
      alone, recipients alone, and in both donor and recipients. The control rats were
      left noninfected. For in vivo cell proliferation, the rats received
      bromedeoxyuridine intravenously 3 h before being killed. RCMV infection
      significantly enhanced the generation of experimental obliterative bronchiolitis
      (OB). First, acute RCMV infection was linked to markedly enhanced MHC class II
      expression on the respiratory epithelium and prominent airway wall inflammation
      of W3/25+ T cells (CD4+) and ED1+/ED2+ macrophages. Second, acute infection
      induced a fivefold increase in luminal occlusion of the trachea, due to
      proliferating inflammatory and alpha-smooth muscle actin+ myofibroblast-like
      cells. Acute RCMV infection was particularly associated with markedly increased
      expression of platelet-derived growth factor (PDGF) AA-isoform in various
      structures of the graft 10 d after transplantation. At 30 d, RCMV significantly
      increased PDGF alpha- and beta-receptor expression in alpha-smooth muscle actin+
      cells and TNF-alpha expression in capillary endothelial cells of the
      fibroproliferative lesion. In chronic recipient RCMV infection, the
      histopathological changes were quite similar to acute infection. Chronic donor
      infection did not amplify the development of experimental OB. As analyzed by
      immunohistochemistry from the grafts and by plaque assays from salivary gland
      biopsies of the recipients, trace RCMV antigen expression, while no infectious
      RCMV could be recovered in the chronic donor infection group. In other infected
      groups, RCMV antigen expression was mild to moderate and salivary glands
      contained plenty of infectious RCMV. To conclude, our results indicate that RCMV
      infection enhances epithelial MHC class II expression and myofibroproliferation
      in heterotopic rat tracheal allografts and suggest that these changes may be
      induced by increased PDGF-AA and PDGF alpha-receptor expression, respectively.

PMID- 9196119
TI  - Pulmonary tumor embolism.

PMID- 9196120
TI  - Nasal mask pressure waveform and inspiratory muscle rest during nasal assisted
      ventilation.
AB  - In mechanically ventilated patients, pressure and flow tracings can be used to
      assess respiratory pump muscle activity or rest. When the ventilation is
      delivered through an endotracheal tube, the respiratory system can be considered
      a one-compartment model, and activation of the respiratory muscles results in
      deformations and variability of the pressure tracings. This is also true when
      mechanical ventilation is delivered nasally. With intermittent positive-pressure
      ventilation delivered through a nasal mask (nIPPV), we have recently shown that
      the glottis can interfere with ventilation even in the absence of diaphragmatic
      surface electromyographic (EMG) activity. On the basis of our observations, we
      suggested that when mechanical ventilation is delivered through a nasal means of
      access, the respiratory system cannot be considered a one-compartment model. To
      confirm this hypothesis, we submitted one healthy subject to nIPPV while his
      glottis was continuously monitored through a fiberoptic bronchoscope and his
      diaphragmatic activity was monitored with a bipolar esophageal electrode. During
      wakefulness or sleep, we observed irregularities in the nasal mask pressure
      waveform, in nasal mask peak pressure, and in actual VT despite the absence of
      respiratory pump muscle activity. These irregularities were related to
      significant variations in the glottic width, rather than to the reappearance of
      transient phasic inspiratory muscle activity. We conclude that during nIPPV,
      deformations in the mask pressure waveform can be induced by variations in the
      glottic aperture without activation of the diaphragm. Thus, when mechanical
      ventilation does not bypass the glottis, the respiratory system does not behave
      like a one-compartment model, and EMG remains the only reliable technique for
      assessing diaphragmatic muscle activity.

PMID- 9196121
TI  - Pseudomonas aeruginosa II lectin stops human ciliary beating: therapeutic
      implications of fucose.
AB  - Respiratory tract infection by Pseudomomas aeruginosa may be life-threatening for
      intensive care patients and patients with cystic fibrosis (CF). The colonization
      of airways can be facilitated by bacterial lectins (carbohydrate-binding
      proteins) that attach bacteria to the glycoconjugates of the mucosa. We show in
      this paper that the fucose-specific lectin P. aeruginosa agglutinin II (PAII)
      produced by these bacteria can, in addition to facilitating bacterial adhesion,
      arrest ciliary beating in human airways in vitro. This inhibitory effect of the
      lectin can be abolished by preincubating PAII with its specific sugar, fucose.
      Furthermore, ciliary beating is completely restored by addition of fucose 2 h
      after administration of PAII to cell cultures. Therefore, adding a simple
      monosaccharide to nebulizers may improve the management of P. aeruginosa
      infection by abrogating the effect of PAII on ciliary beating, thus restoring
      part of the nonspecific pulmonary defense mechanisms of the airways.

PMID- 9196122
TI  - Acute effects of summer air pollution on respiratory health of asthmatic
      children.
AB  - In the early summer of 1995, the acute respiratory effects of ambient air
      pollution were studied in a panel of 61 children, ages 7 to 13 yr, of whom 77%
      were taking asthma medication. Peak flow was measured twice daily with MiniWright
      meters at home and the occurrence of acute respiratory symptoms and medication
      use was registered daily by the parents in a diary. Exposure to air pollution was
      characterized by the ambient concentrations of ozone, PM10, and black smoke.
      During the study period, maximal 1-h ozone concentrations never exceeded 130
      microg/m3, and 24-h black smoke and PM10 concentrations were never higher than 41
      and 60 microg/m3 respectively. Associations of air pollution and health outcomes
      were evaluated using time series analysis. After adjusting for pollen, time
      trend, and day of the week, black smoke in particular was associated with acute
      respiratory symptoms and with medication use. Less strong associations were found
      for PM10 and ozone. These results suggest that in this panel of children, most of
      whom had asthma, relatively low levels of particulate matter and ozone in ambient
      air are able to increase symptoms and medication use.

PMID- 9196123
TI  - Human lung parenchyma retains PM2.5.
AB  - There is extensive epidemiologic evidence that increased levels of the inhalable
      particulate fraction of air pollution (PM10) are associated with increased
      morbidity and mortality. The mechanisms of these effects are unknown, and the
      exact types and sizes of particles responsible are a matter of intense dispute.
      To obtain an idea of the sizes of particles retained in human lung parenchyma, we
      used analytical electron microscopy to count, size, and identify particles in the
      upper lobe apical segment parenchyma of autopsy lung tissue from 10 never-smoking
      long-term residents of Vancouver. The overall geometric mean particle diameter
      (GSD) was 0.38 microm (2.4); within this broad distribution, silica and silicate
      particles had a geometric mean diameter of 0.49 microm (2.2), whereas metals had
      a geometric mean diameter of 0.17 microm (2.0). Ultrafine particles (those with
      diameter < or = 0.1 microm) constituted less than 5% of the total, and most of
      these were metals. Translation of these projected area diameters into aerodynamic
      diameters (d(a)) revealed that 96% of the particles had d(a) less than 2.5. These
      data indicate that human lung parenchyma effectively retains PM2.5, suggesting
      that attempts to determine the particles responsible for chronic particulate
      pollutant effects should concentrate on this size range. These data also suggest
      that several different type/size classes of particle are present in human
      parenchyma, but that ultrafine particles make up only a small fraction of the
      total.

PMID- 9196124
TI  - Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea
      syndrome.

PMID- 9196125
TI  - Latent adenoviral infection in follicular bronchiectasis.

PMID- 9196126
TI  - Diffuse panbronchiolitis in the United States.

PMID- 9196127
TI  - Inflammatory chemical mediators during conventional mechanical ventilation and
      during high frequency oscillatory ventilation.

PMID- 9196128
TI  - Treatment of recurrent ovarian cancer: increasing options--"recurrent" results.

PMID- 9196129
TI  - Kids, cancer, and the Joe Camel connection.

PMID- 9196131
TI  - Tobacco use among pediatric cancer patients: recommendations for developing
      clinical smoking interventions.
AB  - PURPOSE AND METHODS: The current status of tobacco use among young cancer
      patients and the acute and chronic complications associated with tobacco use in
      these patients is reviewed. RESULTS AND CONCLUSION: Studies report that
      adolescent cancer survivors use tobacco as much as their peers who have never
      been treated for cancer, despite the adverse consequences of engaging in this
      unhealthy habit. Health care professionals have the opportunity and
      responsibility to incorporate tobacco counseling as a routine component of
      medical care delivery. Nurse/physician-delivered smoking interventions have been
      found to promote smoking cessation in adults, although little effort has been
      devoted to the development of similarly effective smoking interventions for
      pediatric cancer patients who smoke. Components of existing smoking
      prevention/cessation curricula from successful school-based interventions and
      physician-delivered smoking interventions can be adapted and tailored to
      pediatric cancer patients in medical settings. Smoking interventions that educate
      patients about their increased vulnerability to tobacco-related consequences,
      relative to their healthy peers, may have an enhanced impact. Guidelines for
      conducting a comprehensive assessment of tobacco use and implementing smoking
      interventions with pediatric cancer patients is provided. Strategies for
      modifying the cancer patient's perceived vulnerability to tobacco-related
      consequences is also discussed.

PMID- 9196130
TI  - Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian
      cancer.
AB  - PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter
      study of patients with advanced epithelial ovarian carcinoma who had progressed
      during or after one platinum-based regimen. PATIENTS AND METHODS: Patients
      received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days
      every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21
      days (n = 114). Patients had bidimensionally measurable disease and were assessed
      for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in
      topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients
      (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of
      patients with topotecan and 33% of patients with paclitaxel. Median durations of
      response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P =
      .222) and median times to progression were 23 and 14 weeks, respectively (P =
      .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P
      = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P =
      .303) in resistant patients (not responded to prior platinum-based therapy or
      progressed within 6 months of an initial response) and 28.8% versus 20.0% (P =
      .213) in sensitive patients (progressed > 6 months after response). Neutropenia
      was significantly more frequent on the topotecan arm 79% versus paclitaxel arm
      23% (P < .01). It was short-lasting and noncumulative in both arms.
      Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents.
      CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested
      by the higher response rate and significantly longer time to progression.

PMID- 9196132
TI  - Late mortality of long-term survivors of childhood cancer.
AB  - PURPOSE: To determine the frequency and patterns of late mortality among long
      term survivors of childhood cancer. MATERIALS AND METHODS: Medical records of
      patients who survived at least 5 years after the diagnosis of childhood cancer
      were reviewed to determine the causes of subsequent deaths. Estimated 15-year
      survival and standardized mortality ratios for deaths from nonneoplastic
      treatment complications were compared with adjusted United States population
      estimates. The study included 2,053 patients who had survived > or = 5 years,
      grouped by treatment eras that reflected increased intensity of therapy and
      significantly improved survival (early era, 1962 to 1970; recent era, 1971 to
      1983). RESULTS: There have been 258 subsequent deaths in the 2,053 childhood
      cancer survivors; 169 occurred 5 to 10 years postdiagnosis and 89 > or = 10 years
      post diagnosis. For the study period as a whole, deaths were attributed to
      recurrent primary malignancy in 61% of cases, second malignancy in 20%,
      nonneoplastic treatment complication in 10%, and unintentional injury/suicide in
      8%. Late death from recurrent disease decreased significantly for survivors
      treated in the recent era (P < .0001), while the risk of death from second
      malignancies increased, although not statistically significantly (P = .10).
      Projected 15-year survival estimates for all > or = 5-year survivors in both
      treatment eras was greater than 90%, but differed from expected rates.
      CONCLUSION: Late mortality from recurrence after treatment for childhood cancer
      decreases with more effective initial therapy. Prolonged disease-free status is
      associated with an expected survival that approaches that of the general
      population for patients treated from 1971 through 1983. The impact of more recent
      intensified and novel therapies for high-risk patients remains to be determined.

PMID- 9196133
TI  - Clinical features and treatment outcome of childhood T-lineage acute
      lymphoblastic leukemia according to the apparent maturational stage of T-lineage
      leukemic blasts: a Children's Cancer Group study.
AB  - PURPOSE: Leukemic cells from T-lineage acute lymphoblastic leukemia (ALL)
      patients are thought to originate from T-lymphocyte precursors corresponding to
      discrete stages of T-cell ontogeny. Here we sought to determine the influence of
      leukemic cell apparent maturational stage on treatment outcomes in pediatric T
      lineage ALL. PATIENTS AND METHODS: From 1983 through 1993, 407 pediatric T
      lineage ALL patients were enrolled onto two sequential series of risk-adjusted
      treatment protocols of the Children's Cancer Group. In the current analysis, T
      lineage ALL patients were immunophenotypically classified as follows: CD7+ CD2-
      CD5- pro-thymocyte leukemia (pro-TL), CD7+ (CD2 or CD5)+ CD3- immature TL, and
      CD7+ CD2+ CD5+ CD3+ mature TL. RESULTS: Similar induction outcomes of 91.4%,
      97.1%, and 98.3% were obtained by the pro-, immature, and mature TL groups,
      respectively. Four-year event-free survival (EFS) was lower for pro-TL patients
      (57.1%; SD = 8.4%,) compared with immature and mature TL patients (68.5%; SD =
      3.5%; and 77.1%; SD = 4.0%, respectively) with an overall significance of .05
      (log-rank test) or .04 (log-rank trend test). Relative hazards rates (RHR) were
      2.11 and 1.22 for pro-TL and immature TL versus mature TL, respectively. Highly
      significant differences were found for overall survival (P = .005, log-rank test;
      P = .009, log-rank trend test). Multivariate analysis confirmed that the
      prognostic influence of ontogeny grouping was independent of that of other
      prognostic factors. CONCLUSION: Leukemic cells of the pro-TL maturation stage
      identify a small subgroup of T-lineage ALL patients who have a significantly
      worse EFS outcome than patients whose cells are of a more mature stage of
      development.

PMID- 9196134
TI  - Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic
      significance of slow early response to induction chemotherapy for children and
      adolescents with acute lymphoblastic leukemia and unfavorable presenting
      features: a report from the Children's Cancer Group.
AB  - PURPOSE: Compared with previous Children's Cancer Group (CCG) acute lymphoblastic
      leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76
      trial has effected an improvement in event-free survival (EFS). In an attempt to
      improve EFS further, CCG investigators formulated an augmented BFM (A-BFM)
      regimen that provides prolonged, intensified postinduction chemotherapy relative
      to the CCG-modified BFM regimen. PATIENTS AND METHODS: We tested A-BFM in 101
      patients with ALL and unfavorable presenting features that showed slow early
      response (SER) to induction therapy who attained remission on day 28. Their
      outcome was compared with that of 251 concurrent patients with unfavorable
      presenting features, a rapid early response to therapy (RER), and remission by
      day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS:
      The 4-year EFS rate from the end of induction for SER patients treated with A-BFM
      was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5
      years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was
      rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP)
      occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of
      patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT
      had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION: The toxicity of A-BFM is
      significant, but acceptable. Compared with historical control SER patients
      treated with CCG-modified BFM, A-BFM therapy appears to produce a significant
      improvement in EFS. This is the first study to show that intensive chemotherapy,
      as given in the A-BFM regimen, can abrogate the adverse prognostic significance
      of SER.

PMID- 9196135
TI  - Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia: a
      matched-pair analysis. Berlin-Frankfurt-Munster Study Group.
AB  - PURPOSE: The translocation t(9;22)(q34;q11), known as Philadelphia chromosome
      (Ph1) or its molecular equivalent the expression of BCR-ABL-mRNA, is one of the
      most striking and well-characterized cytogenetic abnormalities in leukemia.
      Although investigated for more than 30 years, it remains unclear whether the Ph1
      is an independent risk factor for outcome of leukemia or not. METHODS: A matched
      pair analysis was performed within a homogeneous group of patients, which
      consisted of children who presented with a first relapse of acute lymphoblastic
      leukemia (ALL) who were treated according to ALL relapse trials (ALL-REZ BFM)
      protocols. A total of 307 patients were eligible for this analysis: 30 positive
      and 277 negative for Ph1. Positive patients were matched exactly for time point
      of relapse (on [during] or off [after cessation of] front-line therapy), site,
      and immunophenotype, and as close as possible for duration of first remission,
      peripheral blast-cell count, WBC count, and year of relapse diagnosis. RESULTS:
      The probability of event-free survival is 0.46 at 5 years for negative and 0.11
      for positive patients, respectively (P = .0006). Multivariate analysis showed
      risk ratios of 4.229 for relapse on therapy, 3.561 for Ph1 and/or expression of
      BCR-ABL- mRNA, 1.691 for high peripheral blast-cell count, and 0.232 for bone
      marrow transplantation. CONCLUSION: It was shown that the Ph1 is indeed an
      independent risk factor in childhood relapsed ALL. There are striking
      similarities between these patients and children at initial diagnosis, as well as
      adult patients. Therefore, it is highly suggestive that the Ph1 is also an
      independent risk factor under all of these circumstances.

PMID- 9196137
TI  - Low risk of secondary leukemias after chemotherapy without mechlorethamine in
      childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group.
AB  - BACKGROUND: In the last two decades, it has become evident that secondary
      leukemias after Hodgkin's disease (HD) are mainly caused by the treatment with
      alkylating agents, especially mechlorethamine. Since 1978, the German-Austrian
      trials for childhood HD have used combined chemoradiotherapy without
      mechlorethamine. PATIENTS AND METHODS: The risk of secondary hematologic
      malignancies (SHM) was assessed in the total cohort of 667 children treated in
      four consecutive German-Austrian trials between 1978 and 1990. Primary
      chemotherapy for stages IA/B and IIA consisted of two cycles of vincristine,
      procarbazine, prednisone, and doxorubicin (OPPA) or OPA (without procarbazine)
      and, for more advanced stages, of two cycles of OPPA or OPA plus two, four, or
      six cycles of COPP or COMP (C, cyclophosphamide; M, methotrexate). Radiotherapy
      was given in the first study to extended fields, and in later trials to involved
      fields only. In 591 patients, only primary therapy was given; 76 patients (11%)
      needed additional salvage therapy. The actuarial survival rate at 15 years is
      94%. RESULTS: SHM developed in 5 of 667 patients: four acute myeloid leukemias
      (AMLs) and one myelodysplastic syndrome (MDS). The estimated cumulative risk for
      SHM at 15 years is 1.1% (95% CI, 0.0% to 2.2%). Salvage therapy was a significant
      risk factor for SHM (relative risk, 7.25; P = .03), whereas age, sex, stage of
      HD, splenectomy, and amount of alkylating agents were not. CONCLUSION: The
      observed risk of SHM is smaller than in other studies (adults and children) in
      which chemotherapy with mechlorethamine, vincristine, procarbazine, and
      prednisone (MOPP) was given. This difference can be attributed to the lower
      cumulative doses of alkylating agents, the absence of mechlorethamine in the
      chemotherapy, and the small number of patients who needed salvage therapy in the
      presented cohort. In general, differences in the incidence of SHM after HD
      reflect complex differences between treatment strategies.

PMID- 9196136
TI  - Late effects of allogeneic bone marrow transplantation for children with acute
      myeloblastic leukemia in first complete remission: the impact of conditioning
      regimen without total-body irradiation--a report from the Societe Francaise de
      Greffe de Moelle.
AB  - PURPOSE: To evaluate growth, thyroid function, puberty, cardiac function, and the
      incidence of cataracts in children who received allogeneic bone marrow
      transplantation (BMT) for acute myeloblastic leukemia (AML) in first complete
      remission (CR) after a preparation with or without total-body irradiation (TBI).
      PATIENTS AND METHODS: Among 45 children studied, 26 received busulfan
      cyclophosphamide (Bu-Cy) in preparation for transplantation and 19 received TBI.
      TBI was fractionated in nine cases and delivered as a single dose in 10. Four
      children in the Bu-Cy group and none in the TBI group had received prior cranial
      radiation. The mean follow-up duration after BMT was 5.9 years for the whole
      group. RESULTS: The mean cumulative changes in height SD score (SDS) were -0.86
      at 3 years and -1.56 at 5 years in the TBI group, whereas these changes were only
      -0.05 and -0.17 in the Bu-Cy group (P < .01 at 3 and 5 years). The 6-year
      probability of hypothyroidism was 9% +/- 8% in the Bu-Cy group and 43% +/- 15%
      after TBI (P < .02). Pubertal development after Bu-Cy was assessable in two girls
      and five boys: both girls had primary ovarian failure, whereas Leydig cell
      function appeared to be preserved in the five boys. One child who had received
      anthracycline when he was less than 1 year old developed cardiac dysfunction 4
      years after Bu-Cy. The 6-year probability of cataracts was 70% +/- 13% in the TBI
      group and 0% after Bu-Cy. CONCLUSION: The use of Bu-Cy represents an alternative
      transplant cytoreductive regimen for children with AML in first CR, which can
      reduce the risk of posttransplant growth impairment, thyroid dysfunction, Leydig
      cell damage, and the incidence of cataracts.

PMID- 9196138
TI  - Cytotoxic therapy-induced D-xylose malabsorption and invasive infection during
      remission-induction therapy for acute myeloid leukemia in adults.
AB  - PURPOSE: To study the sequential changes in the intestinal absorption of an oral
      pentose probe, D-xylose, in patients receiving therapy for untreated acute
      myeloid leukemia (AML), and to correlate these changes to infectious morbidity.
      PATIENTS AND METHODS: Serial D-xylose absorption studies were conducted in 110
      consecutive adult patients admitted to a university-affiliated tertiary care
      hospital for remission-induction therapy for untreated newly diagnosed AML.
      Serial serum D-xylose levels were obtained 1 hour after a 5-g oral dose of D
      xylose at baseline and weekly for 4 weeks until marrow recovery. These results
      were correlated with invasive infection using multivariate techniques. RESULTS:
      The mean (+/- SEM) serum D-xylose levels were 0.88 +/- 0.03, 0.69 +/- 0.03, 0.58
      +/- 0.02, 0.53 +/- 0.02, and 0.73 +/- 0.02 mmol/L at baseline and weeks 1 to 4,
      respectively (P < .0001, analysis of variance [AN-OVA]). Time to malabsorption
      varied with induction regimen (P = .007, log-rank test). Bloodstream infections
      during week 2 correlated with malabsorption (P = .007). Neutropenic enterocolitis
      correlated independently with induction regimen (P = .009), malabsorption at week
      2 (P = .02), and the development of candidemia (P = .005). Hepatosplenic fungal
      infection correlated with induction regimen (P = .03), malabsorption at week 2 (P
      = .02), and fever at diagnosis (P = .003). Malabsorption was unrelated to the
      duration of severe neutropenia and the administration of parenteral nutrition.
      CONCLUSION: Serial D-xylose absorption studies in subjects with AML produced a
      characteristic profile of cytotoxic therapy-related damage to the functional
      integrity of the intestinal epithelium that was regimen dependent,
      myelosuppression independent, and predictive for invasive infectious
      complications. Further study to validate these observations appears warranted.

PMID- 9196139
TI  - Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid
      leukemia blasts identifies a group of patients with poor response to intensive
      chemotherapy.
AB  - PURPOSE: c-mpl, the human homolog of v-mpl, is the receptor for thrombopoietin.
      Given that c-mpl expression carries an adverse prognosis in myelodysplastic
      syndrome and given the prognostic significance of expression of other growth
      factor receptors in other diseases, we attempted to determine whether c-mp/mRNA
      expression is a prognostic factor in acute myeloid leukemia (AML). PATIENTS AND
      METHODS: We analyzed bone marrow samples from 45 newly diagnosed AML patients by
      reverse-transcription polymerase chain reaction. RESULTS: Samples from 27
      patients (60%) expressed c-mpl mRNA (c-mpl+); their clinical and laboratory
      features were compared with those of the 18 patients without detectable levels of
      c-mpl(c-mpl-). No significant differences in age, sex, leukocyte count, French
      American-British subtype, or karyotype group were found. c-mpl+ patients more
      commonly had secondary AML (41% v 11%; P = .046) and more commonly expressed CD34
      (67% v 12%; P = .0004). There was no significant difference in complete remission
      (CR) rate. However, c-mpl+ patients had shorter CR durations (P = .008; median,
      6.0 v > 17.0 months). This was true when only de novo AML patients were
      considered and when controlling for age, cytogenetics, or CD34 expression. There
      was a trend toward shorter survival in c-mpl+ patients (P = .058; median, 7.8 v
      9.0 months). CONCLUSION: These data suggest that c-mpl expression is an adverse
      prognostic factor for treatment outcome in adult AML that must be considered in
      the analysis of clinical studies using thrombopoietin in AML.

PMID- 9196140
TI  - Acyclovir prophylaxis and fever during remission-induction therapy of patients
      with acute myeloid leukemia: a randomized, double-blind, placebo-controlled
      trial.
AB  - PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to
      estimate the preventive effect of the antiherpetic drug acyclovir on fever,
      incidence of bacteremia, use of antibiotics, and presentation of infections in
      patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Ninety herpes
      simplex virus (HSV)-seropositive patients aged 18 to 84 years were included.
      Forty-five patients received acyclovir (800 mg by mouth daily) and 45 placebo.
      The patients were examined daily for 28 days from the initiation of remission
      induction chemotherapy. RESULTS: Fever developed in all patients in both groups.
      Acyclovir prophylaxis postponed the development of an oral temperature > or =
      38.0 degrees C by 3 days (95% confidence interval [CI], 1 to 4 days; P = .03) and
      the initiation of antibacterial treatment by 3 days (95% CI, 1 to 5 days; P =
      .008). The duration of fever, use of antibacterial treatment, incidence of
      bacteremia, and need for systemic antifungal therapy were not affected by
      acyclovir prophylaxis. At fever development, acyclovir prophylaxis affected the
      incidence and localization pattern of oral ulcers. Thus, in the acyclovir group,
      the number of nonfungal oral infections was reduced (relative risk, 0.45 [95% CI,
      0.24 to 0.85]) and mainly located on the soft palate (relative risk, 2.49 [95%
      CI, 1.19 to 5.22]). CONCLUSION: Acyclovir prophylaxis has an impact on fever
      development, but not on the duration of fever or the need for antibiotics. It
      does not reduce the incidence of bacteremia, but the presentation of acute oral
      infections is changed.

PMID- 9196141
TI  - Dose-response relationship of complementary radiotherapy following four cycles of
      combination chemotherapy in intermediate-stage Hodgkin's disease.
AB  - PURPOSE: To determine the appropriate irradiation dose after four cycles of
      modern combination chemotherapy in nonbulky involved field (IF/BF) and
      noninvolved extended-field (EF/IF) sites in patients with intermediate-stage
      Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA
      with a large mediastinal mass, E stage, or massive spleen involvement were
      treated with two double cycles of alternating cyclophosphamide, vincristine,
      procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and
      dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and
      HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy
      were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF
      irradiation in all fields outside bulky disease sites. A cohort of 111 patients
      who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to
      1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS:
      Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no
      differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities
      were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18
      of 26 relapsing patients either failed to respond in initial bulky sites (n = 5)
      or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the
      cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation.
      CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy
      dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4
      months of modern polychemotherapy in patients with intermediate-stage HD. Relapse
      patterns indicate that patients destined to relapse need more systemic, rather
      than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in
      EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

PMID- 9196143
TI  - Predictive capacity of the International Prognostic Factor Index in patients with
      peripheral T-cell lymphoma.
AB  - PURPOSE: The International Prognostic Factor Index has been shown to predict the
      outcome of patients with predominantly B-cell lymphomas classified using
      traditional classifications, including the Working Formulation, but its
      prognostic importance has not been tested in a cohort of patients with
      exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic
      significance of the International Prognostic Factor Index in patients with
      peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Seventy-eight patients
      (48 men and 30 women) with PTCL seen at a single institution between 1985 and
      1995 were included in the analysis. The morphology and immunocytochemistry of all
      the original biopsy specimens were reviewed by a single pathologist and
      classified using the Revised European-American Lymphoma (REAL) classification.
      The International Prognostic Factor Index, as well as clinical and biochemical
      parameters, were evaluated by univariate and multivariate analyses to determine
      their association with patient outcome. RESULTS: The International Prognostic
      Factor Index strongly predicted survival when all patients were included in the
      analysis (P < .001). For patients < or = 60 years, the age-adjusted International
      Index significantly predicted long-term survival (P = .0218). For patients older
      than 60 years, the age-adjusted International Index also significantly predicted
      survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P
      = .014) were also significant prognostic factors in the univariate analysis, but
      only the International Index remained significant in the multivariate analysis (P
      = .001). CONCLUSION: The International Prognostic Factor Index, which
      significantly predicts outcome in patients with aggressive/intermediate-grade B
      cell lymphomas, has similar prognostic importance in patients with PTCL.

PMID- 9196142
TI  - Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell
      transplants for follicular lymphoma: a pilot study.
AB  - PURPOSE: A pilot study to validate the use of CD34+ selection (Ceprate SC) of
      blood stem-cell collection in patients with advanced follicular lymphoma
      receiving myeloablative chemoradiotherapy. PATIENTS AND METHODS: Seventeen
      patients were entered onto the protocol. Thirteen of 17 patients have undergone
      transplantation; the median age is 42.5 years (range, 33 to 51), seven of 13 are
      stage IVB, two stage IVA, three stage IIIB, and one stage IIB. All except two
      patients were treated after first or subsequent relapses after receiving
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to
      achieve a good partial (six of 13) or complete (seven of 13) response before stem
      cell mobilization with cyclophosphamide 3 g/m2 and filgrastim 300 microg once
      daily. RESULTS: Eleven of 13 patients had a detectable t(14;18) by nested
      polymerase chain reaction (PCR). Median CD34+ count before selection was 2.9 x
      10(6)/kg (range, 1.17 to 11.3) and after CD34+ selection was 1.54 x 10(6)/kg
      (range, 0.88 to 7.6) with a median CD34+ yield of 62.4% (range, 17% to 95%) and
      purity of 60% (range, 39.3% to 73%). Of the 11 patients known to have t(14;18),
      10 had PCR-detectable contamination of stem-cell harvests that became PCR
      negative in six of the 10 after CD34+ selection. Engraftment was rapid with a
      median day to absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L of 13
      days (range, 11 to 21) and platelet count greater than 20 x 10(9)/L of 14 days
      (range, 10 to 44). With a median follow-up duration of 15 months, three patients
      have remained persistently PCR-positive, two of whom received PCR-positive stem
      cells. Two have relapsed. Of the seven patients who received PCR-negative stem
      cells, five have had no PCR-detectable disease in posttransplant bone marrow
      samples. CONCLUSION: Longer follow-up duration is required to determine the
      significance of these findings, but we have confirmed the feasibility of CD34+
      selected cells to deplete peripheral-blood stem cells of tumor cells from
      patients undergoing high-dose therapy for follicular lymphoma.

PMID- 9196144
TI  - Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy
      added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive
      estrogen and/or progesterone receptor-positive breast cancer: a report of the
      National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site
      Group.
AB  - PURPOSE AND METHODS: By the mid 1980s, tamoxifen alone was considered standard
      adjuvant therapy for postmenopausal women with node-positive, estrogen receptor
      (ER)- or progesterone receptor (PgR)-positive breast cancer. From 1984 through
      1990, 705 eligible postmenopausal women with node-positive, ER- or PgR-positive
      breast cancer were randomized to a National Cancer Institute of Canada Clinical
      Trials Group (NCIC CTG) study that compared tamoxifen 30 mg by mouth daily for 2
      years (TAM) versus TAM plus chemotherapy with all-intravenous cyclophosphamide
      600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 given every 21 days
      for eight cycles (CMF). RESULTS: There were no significant differences in overall
      survival, recurrence-free survival, locoregional recurrence-free survival, or
      distant recurrence-free survival between the two treatment arms. However, there
      was significantly greater severe toxicity, which included leukopenia (P < .0001),
      nausea and vomiting (P < .0001), and thromboembolic events (P < .0001), as well
      as significantly more mild or greater toxicity, which included thrombocytopenia
      (P = .04), anemia (P = .02), infection (P = .0004), mucositis (P = .0001),
      diarrhea (P = .0001), and neurologic toxicity (P = .006), in women who received
      TAM plus CMF. CONCLUSION: The addition of CMF to TAM adds no benefit and
      considerable toxicity in this group of women.

PMID- 9196145
TI  - Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as
      adjuvant treatment in operable breast cancer with 10 or more involved axillary
      nodes: five-year results.
AB  - PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy
      administered as adjuvant initial treatment to women with breast cancer with
      extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with
      stage II to III breast cancer involving > or = 10 axillary nodes received a novel
      high-dose sequential (HDS) regimen, including the high-dose administration of
      three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan)
      given within the shortest interval of time as possible with hematologic and
      nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as
      planned, one patient died of acute toxicity, and three patients were switched to
      standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months
      and a lead follow-up of 78 months, actuarial relapse-free survival for all 67
      registered patients is 57% and overall survival is 70%, respectively. Comparison
      with a historical control group of 58 consecutive patients showed a significantly
      superior rate of freedom from relapse for the HDS-treated group (57% v 41%,
      respectively), in particular when two subgroups of patients, more homogeneous for
      their number of involved nodes, were compared (65% v 42%). Overall, treatment was
      of short duration (median, 70 days), required a median of 32 days of hospital
      stay, and was associated with only a few severe side effects (the most
      distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS
      therapy emerges as an effective and applicable regimen, whose major toxicity was
      occasional. Final assessment of its value in a randomized, multicenter trial is
      presently underway.

PMID- 9196146
TI  - Use of Truquant BR radioimmunoassay for early detection of breast cancer
      recurrence in patients with stage II and stage III disease.
AB  - PURPOSE: The Truquant BR radioimmunoassay (RIA) (Biomira Diagnostics Inc,
      Rexdale, Canada) uses the monoclonal antibody B27.29 to quantitate the MUC-1 gene
      product (CA 27.29 antigen) in serum. We evaluated CA 27.29 antigen in a
      controlled, prospective clinical trial for its ability to predict relapse in
      stage II and stage III breast cancer patients. PATIENTS AND METHODS: Over a 2
      year period, 166 patients who had completed therapy for stage II (80.1%) or III
      (19.9%) breast cancer and were clinically free of disease were serially tested
      for CA 27.29 antigen levels. The study was double-masked and cancer recurrence
      was documented based on clinical findings. Patients with two consecutive CA 27.29
      antigen test results above the upper limit of normal were considered positive.
      RESULTS: The Truquant BR RIA had a sensitivity of 57.7%, specificity of 97.9%,
      positive predictive value of 83.3%, and negative predictive value of 92.6%. The
      recurrence rate was 15.7%. A Cox regression analysis showed that the only
      variable to correlate with recurrent disease was the CA 27.29 antigen test
      result. Patients with a positive test result had increased odds of having a
      recurrence (odds ratio, 6.8; P < .00001). The test was effective in predicting
      recurrence in patients with both distant and locoregional disease. In a subgroup
      of patients with bone pain, CA 27.29 antigen level was found to identify reliably
      patients who would subsequently develop recurrent disease. CONCLUSION: These data
      demonstrate that the Truquant BR RIA can be used as an aid to predict recurrent
      breast cancer in patients with stage II and III disease.

PMID- 9196147
TI  - Race and clinical outcome in breast cancer in a series with long-term follow-up
      evaluation.
AB  - PURPOSE: To compare the outcome of African American (AA) and Caucasian (C) breast
      cancer patients who had equivalent disease extent and were similarly treated.
      PATIENTS AND METHODS: We compared prognostic characteristics, treatment, and
      outcome of 1,037 C and 481 AA breast cancer patients treated with mastectomy
      between 1946 and 1987. The median follow-up duration was 15.6 years. RESULTS:
      During the study period, there was a successive increase in the percent of
      patients who presented with early breast cancer. Between 1980 and 1987, 35.1% AA
      versus 47.6% C patients had < or = 2-cm tumors and 50.0% AA versus 61.9% C
      patients were node-negative, while between 1946 and 1959, 27.7% AA and 31.3% C
      had < or = 2-cm tumors and 41.5% AA versus 40.4% C patients were node-negative.
      The treatments were similar during the study period. The 20-year disease-free
      survival (DFS) rate of AA compared with C patients with node-negative < or = 2
      cm, 2.1- to 4-cm, and greater than 4-cm tumors and of patients with one to three
      and > or = four positive nodes was not significantly different. Equal-size tumors
      had similar proportion of positive axillary nodes in AA compared with C patients.
      The DFS for AA patients compared with C patients was similar in the periods 1946
      to 1959, 1960 to 1969, and 1970 to 1979, but was lower between 1980 and 1987 (P =
      .02). In multivariable analysis, race was not a significant variable. CONCLUSION:
      In this large group of uniformly treated breast cancer patients, race was not an
      independent factor that influenced outcome. The racial differences seen between
      1980 and 1987 are likely because of a larger percent of greater than 2-cm and
      node-positive tumors in AA patients. Education and access to early diagnosis
      should reduce or eliminate the racial differences seen.

PMID- 9196148
TI  - Age-related patterns of care: evidence against ageism in the treatment of early
      stage breast cancer.
AB  - PURPOSE: To assess whether the use of adjuvant systemic therapy in postmenopausal
      women with early-stage breast cancer is influenced by patient age. METHODS: A
      retrospective cohort study based on data collected from medical records and from
      patients and their surgeons was performed among 746 postmenopausal patients
      diagnosed with early-stage breast cancer at 30 hospitals located throughout
      Minnesota. The adjusted odds of receiving hormonal therapy, chemotherapy, and
      both hormonal therapy and chemotherapy as a function of age was determined.
      RESULTS: Among women with negative lymph nodes, 62% received some form of
      adjuvant drug therapy. For these women, the likelihood of receiving hormonal
      therapy or both hormonal therapy and chemotherapy did not vary with patient age
      and the likelihood of receiving chemotherapy declined with age. Among women with
      positive lymph nodes, 92% received some form of adjuvant therapy. For these
      women, the likelihood of receiving hormonal therapy increased with age and the
      likelihood of receiving chemotherapy declined with age, as did the likelihood of
      receiving both hormonal therapy and chemotherapy. CONCLUSION: The observed
      associations between age and the use of adjuvant systemic therapy appear to
      reflect, in general, available information about treatment efficacy and do not
      suggest underuse among elderly women with early-stage breast cancer. The use of
      adjuvant therapy depends on clinical factors that predict the increased risk of
      metastases or the increased likelihood of response to treatment, rather than
      other sociodemographic factors. Our results also suggest that younger
      postmenopausal women with positive lymph nodes compared with older women may be
      undertreated with respect to tamoxifen because of the substitution of
      chemotherapy for hormonal therapy.

PMID- 9196149
TI  - Sentinel lymphadenectomy in breast cancer.
AB  - PURPOSE: We previously demonstrated increased detection of axillary metastases
      using sentinel lymphadenectomy (SLND) and immunohistochemistry. These methods
      have evolved and we now report our current use of these techniques and our most
      recent results of axillary staging with SLND. PATIENTS AND METHODS: One hundred
      seven consecutive women (previously unreported) with breast cancer underwent SLND
      followed by completion axillary lymphadenectomy (ALND). All sentinel nodes were
      examined intraoperatively with frozen section and postoperatively with
      hematoxylin and eosin staining (H&E) plus immunohistochemical staining (IHC)
      using antibody to cytokeratin. The nonsentinel axillary nodes were examined with
      H&E, but not IHC. RESULTS: The median age was 56.6 years (range, 28 to 90). Most
      patients (58.9%) were postmenopausal, most primary tumors (62.6%) were palpable,
      and most operations (86.9%) were breast-conserving. The mean tumor size was 2.11
      +/- 1.38 cm. Sentinel nodes were identified in 100 patients: 42 patients had
      metastases in sentinel nodes; of these, 28 (66.7%) had no other involved axillary
      nodes. On average, 1.8 +/- 1.1 sentinel nodes were examined and 20.3 +/- 7.8
      nonsentinel nodes were removed. Of seven patients with no identified sentinel
      nodes, six had a tumor-negative axilla. SLND was 100% predictive of axillary
      status in these 100 women. CONCLUSION: In this population of breast cancer
      patients, SLND with frozen section and IHC was a minimally invasive, highly
      accurate intraoperative method of axillary staging. We are evaluating the
      elimination of routine ALND for sentinel-node negative women to minimize the
      morbidity associated with standard dissections. The ability to identify node
      negative patients without ALND would be a welcome addition to the management of
      women with breast cancer.

PMID- 9196150
TI  - Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on
      projections from Eastern Cooperative Oncology Group 1684.
AB  - PURPOSE: Interferon alfa-2b (IFN) in a randomized clinical trial (E1684)
      prolonged relapse-free and total survival in high-risk resected melanoma.
      However, the costs and toxicities of IFN are barriers to its widespread use. This
      study was undertaken to analyze the projected costs and long-term benefits of IFN
      by combining prospectively collected data on IFN actual dosage, time of
      recurrence, and survival with secondary data on long-term melanoma recurrence
      risks to project the cost-effectiveness of adjuvant IFN compared with
      observation. PATIENTS AND METHODS: Two hypothetical cohorts of 50-year-old
      melanoma patients whose mean IFN dosage and clinical results were directly taken
      from E1684 were included in the study. Melanoma recurrence risks beyond 5 years
      were derived from international databases. Melanoma recurrence care costs and
      quality-of-life adjustments, when considered, were based on expert consensus. End
      points were incremental costs, life-years gained, and cost per life-year gained
      with and without quality-of-life adjustments. RESULTS: The IFN cohort was
      projected to have an increased (undiscounted) survival of 0.52 years at 7 years
      and 1.90 years over a lifetime. The projected incremental cost (in 1996 United
      States dollars) per life-year gained in the IFN cohort ranged from $13,700 after
      35 years to $32,600 at 7 years, the median follow-up of E1684. Using assigned
      quality-of-life values for IFN and recurrence, the lifetime cost per quality
      adjusted life-year increased to $15,200. Even if treatment costs for recurrence
      were excluded, the lifetime incremental cost per life-year gained was $21,600.
      CONCLUSION: The cost and toxicity of IFN must be balanced against its projected
      benefits in high-risk melanoma. The derived cost-effectiveness and cost-utility
      ratios for IFN were comparable to other cancer interventions for which cost
      effectiveness analysis has been performed.

PMID- 9196151
TI  - Autologous hapten-modified melanoma vaccine as postsurgical adjuvant treatment
      after resection of nodal metastases.
AB  - PURPOSE: To determine whether treatment with an autologous whole-cell vaccine
      modified with the hapten dinitrophenyl (DNP vaccine) is an effective postsurgical
      adjuvant treatment for melanoma patients with clinically evident nodal
      metastases. PATIENTS AND METHODS: Eligible patients had regional nodal metastases
      that were large enough (> or = 3 cm diameter) to prepare vaccine. Following
      standard lymphadenectomy, patients were treated with DNP vaccine on a monthly or
      weekly schedule. RESULTS: Of 62 patients with metastasis in a single lymph node
      bed (stage III), 36 are alive after a median follow-up time of 55 months (range,
      29 to 76); the projected 5-year relapse-free and overall survival rates are 45%
      and 58%, respectively. Of 15 patients with metastases in two nodal sites, five
      are alive with a median follow-up time of 73 months. An unexpected finding was
      the significantly better survival of older patients; the projected 5-year
      survival of patients greater than 50 versus < or = 50 years was 71% and 47%,
      respectively (P = .011, log-rank test). The development of a positive delayed
      type hypersensitivity (DTH) response to unmodified autologous melanoma cells was
      associated with significantly longer 5-year survival (71% v 49%; P = .031).
      Finally, the median survival time from date of first recurrence was significantly
      longer for patients whose subcutaneous recurrence exhibited an inflammatory
      response (> 19.4 v 5.9 months; P < .001). CONCLUSION: Postsurgical adjuvant
      therapy with autologous DNP-modified vaccine appears to produce survival rates
      that are markedly higher than have been reported with surgery alone. Moreover,
      this approach has some intriguing immunobiologic features that might provide
      insights into the human tumor-host relationship.

PMID- 9196152
TI  - Treatment of Kaposi's sarcoma after solid organ transplantation.
AB  - PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma
      (KS) after solid organ transplantation at a single institution was undertaken to
      define the clinical presentation of this malignancy in the setting of iatrogenic
      immunodeficiency, and to determine the most appropriate treatment for patients in
      this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who
      underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital
      between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were
      identified who developed biopsy-proven KS in the posttransplantation period. Five
      patients who had disseminated KS who had not responded to either reduction or
      withdrawal of immunosuppression or to local radiotherapy were treated with
      combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10
      mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks.
      RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was
      limited to a localized area of the skin for only six patients, all after kidney
      transplantation. Visceral KS was present in three patients. Four of five patients
      responded to ABV chemotherapy (two complete and two partial remissions). The
      fifth patient responded to second-line etoposide and cisplatin. The median
      duration of response was in excess of 13 months (range, 8+ to 45+ months).
      Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity.
      CONCLUSION: KS is an uncommon but recognized complication of solid organ
      transplantation. Combination chemotherapy is a safe and effective treatment for
      patients with disseminated or visceral KS that fails to respond to changes in
      immunosuppression.

PMID- 9196154
TI  - Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin,
      and extended-schedule etoposide.
AB  - PURPOSE: To evaluate the efficacy and toxicity of a novel chemotherapy
      combination that includes paclitaxel, carboplatin, and extended-schedule
      etoposide in the treatment of patients with carcinoma of unknown primary tumor
      site. PATIENTS AND METHODS: Fifty-five patients with carcinoma of unknown primary
      tumor site were treated with the following regimen, administered every 21 days:
      paclitaxel 200 mg/m2 by 1-hour intravenous (I.V.) infusion on day 1, carboplatin
      at an estimated area under the concentration-time curve (AUC) of 6.0 on day 1,
      and etoposide 50 mg alternated with 100 mg orally on days 1 through 10.
      Responding patients received a total of four courses of treatment. The following
      histologies were included: adenocarcinoma, 30 patients; poorly differentiated
      carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA), 21; poorly
      differentiated neuroendocrine carcinoma, three; and squamous carcinoma, one.
      RESULTS: Twenty-five of 53 assessable patients (47%; 95% confidence interval
      [CI], 33% to 61%) had major objective responses to treatment (seven complete
      responses). Response rates were similar in patients with adenocarcinoma versus
      PDC (45% and 48%, respectively). The actuarial median survival time for the
      entire group was 13.4 months. The regimen was well tolerated, with only seven
      hospitalizations for treatment of neutropenia and fever (4% of courses) and no
      treatment-related deaths. CONCLUSION: The combination of paclitaxel, carboplatin,
      and extended-schedule etoposide is highly active and well tolerated in patients
      with carcinoma of unknown primary tumor site. Response rates and survival in this
      multicenter community-based trial compare favorably with all previously studied
      empiric regimens. In addition, this regimen is substantially less toxic and
      easier to administer than the cisplatin-based regimens previously used in this
      setting. If this level of efficacy is confirmed, this treatment should be
      considered standard first-line therapy in patients with carcinoma of unknown
      primary tumor site.

PMID- 9196153
TI  - High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and
      pilot studies--dose-response and schedule dependence.
AB  - PURPOSE: To evaluate the efficacy and feasibility of high-dose ifosfamide (HDI)
      at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte
      colony-stimulating factor (G-CSF) in adult patients with sarcomas. PATIENTS AND
      METHODS: Between July 1991 and February 1994, 74 patients with sarcomas (37 bone
      and 37 soft tissue) were treated on two simultaneous phase II studies that
      evaluated HDI given as a continuous infusion over 74 hours. G-CSF was started on
      day 5 at 5 microg/kg/d until recovery of granulocyte count. Additionally, between
      March 1993 and March 1994, 15 similar patients with previously treated bone or
      soft tissue sarcomas were treated on a pilot study in which the same total dose
      of ifosfamide was administered by a bolus schedule, along with mesna and G-CSF.
      Patients were treated until maximal response, and where possible, surgical
      resection of gross disease was performed. RESULTS: Seventy-two patients from the
      phase II study using continuous infusion are assessable for response. Four
      complete responses (CRs) and 17 partial responses (PRs) were noted, for an
      overall response rate of 29% (95% confidence interval [CI], 19% to 39%). The
      response rate was 40% (95% CI, 24% to 56%) for bone sarcomas and 19% (95% CI, 6%
      to 32%) for soft tissue sarcomas. Fourteen patients from the pilot study that
      used a bolus schedule are assessable for response. One CR and seven PRs were
      noted, for an overall response rate of 57% (95% CI, 31% to 83%) and a response
      rate of 45% for soft tissue sarcomas. Two patients developed grade 3 to 4 renal
      toxicity, three developed grade 3 CNS toxicity, one had possible grade 3 cardiac
      toxicity, and two developed severe painful peripheral neuropathy. There were no
      treatment-related deaths. CONCLUSION: HDI at 14 g/m2 with mesna and G-CSF is an
      active salvage regimen for patients with bone and soft tissue sarcomas. There is
      a definite positive dose-response curve, and bolus administration appears to be
      more active than continuous infusion.

PMID- 9196155
TI  - Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx.
AB  - PURPOSE: To report the results of radiotherapy alone for stage T3 squamous cell
      carcinoma of the true vocal cord and compare these data with those obtained with
      other treatment modalities. METHODS AND MATERIALS: Seventy-five patients with
      previously untreated T3 squamous cell carcinoma of the glottic larynx were
      treated with curative intent with radiotherapy alone (73 patients) or followed by
      a planned neck dissection (two patients) at the University of Florida between
      September 1966 and August 1994. No patient received adjuvant chemotherapy. All
      patients were monitored for at least 2 years and 85% had a minimum follow-up
      duration of 5 years. No patient was lost to follow-up evaluation. RESULTS: The 5
      year local control and ultimate local control rates were 63% and 86%,
      respectively. The volume of the primary tumor (which was calculated on
      pretreatment computed tomographic [CT] scans in 38 patients) was inversely
      related to local control with larynx preservation: < or = 3.5 cm3, 20 of 23 (87%)
      versus greater than 3.5 cm3, four of 14 (29%) (P = .0005). There was no apparent
      relationship between local control after radiotherapy as a function of whether
      the vocal cord regained mobility or remained fixed during or shortly after
      completion of treatment. The 5-year absolute and cause-specific survival rates
      were 54% and 78%, respectively. Multivariate analysis showed that pretreatment
      tracheostomy was significantly related to diminished cause-specific survival (P =
      .0345). CONCLUSION: Radiotherapy alone results in long-term local-regional
      control and survival rates that are comparable to those obtained with surgery. It
      is unclear whether induction or concomitant chemotherapy is associated with
      improved local-regional control and survival compared with radiotherapy alone.

PMID- 9196156
TI  - Improvements in survival and clinical benefit with gemcitabine as first-line
      therapy for patients with advanced pancreas cancer: a randomized trial.
AB  - PURPOSE: Most patients with advanced pancreas cancer experience pain and must
      limit their daily activities because of tumor-related symptoms. To date, no
      treatment has had a significant impact on the disease. In early studies with
      gemcitabine, patients with pancreas cancer experienced an improvement in disease
      related symptoms. Based on those findings, a definitive trial was performed to
      assess the effectiveness of gemcitabine in patients with newly diagnosed advanced
      pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with
      advanced symptomatic pancreas cancer completed a lead-in period to characterize
      and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2
      weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter
      (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The
      primary efficacy measure was clinical benefit response, which was a composite of
      measurements of pain (analgesic consumption and pain intensity), Karnofsky
      performance status, and weight. Clinical benefit required a sustained (> or = 4
      weeks) improvement in at least one parameter without worsening in any others.
      Other measures of efficacy included response rate, time to progressive disease,
      and survival. RESULTS: Clinical benefit response was experienced by 23.8% of
      gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P =
      .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine
      treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at
      12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment
      was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more
      effective than 5-FU in alleviation of some disease-related symptoms in patients
      with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest
      survival advantage over treatment with 5-FU.

PMID- 9196157
TI  - Phase II trial of paclitaxel and granulocyte colony-stimulating factor in
      patients with pancreatic carcinoma: a Southwest Oncology Group study.
AB  - PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically
      unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer
      palliation, but more effective therapy is needed. This trial evaluated the
      effects of an aggressive schedule of paclitaxel given with granulocyte colony
      stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS
      AND METHODS: All patients were required to have a histologic diagnosis of
      pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or
      radiation therapy. Patients had to have performance status of 0 to 2,
      pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count
      greater than or equal to the institutional lower limit of normal. Following
      pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients
      received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated
      every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or
      until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were
      obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS:
      Forty-five patients were entered onto this study, with six ineligible. For the 39
      eligible patients, there was one complete response (CR) and two partial responses
      (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six
      patients whose assessment was inadequate to determine response. The response rate
      was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The
      median survival time for the 39 eligible patients was 5 months. The most common
      toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue,
      nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function
      abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent
      paclitaxel in this dose and schedule has minimal activity in pancreatic
      adenocarcinoma patients.

PMID- 9196158
TI  - Growth of newly diagnosed, untreated metastatic gastrinomas and predictors of
      growth patterns.
AB  - PURPOSE: The growth pattern of untreated metastatic neuroendocrine tumors is
      unknown. This uncertainty contributes to the disagreement regarding timing and
      could effect evaluation of the efficacy of antitumor treatment. The purpose of
      this study was to determine the growth rate of untreated hepatic metastatic
      gastrinoma and to identify its predictors. PATIENTS AND METHODS: Nineteen
      patients with histologically proven metastatic gastrinoma in the liver with
      Zollinger-Ellison syndrome were studied. Conventional imaging studies were
      performed initially and at 4- to 6-month intervals before any treatment.
      Metastases growth rates were calculated and correlated with laboratory and
      clinical parameters, as well as tumor extent on initial tumor assessment.
      RESULTS: Twenty-six percent of patients (five of 19) demonstrated no growth over
      a mean follow-up time of 29 months, 32% (six of 19) had slow growth (1% to 50%
      increase in volume per month) over a 19-month period, and 42% (eight of 19) had
      rapid growth (> 50% volume increase per month) over an 11-month period. In
      patients with rapid growth, 62% died; 0% of the no-growth or slow-growth group
      died. No clinical or laboratory parameter correlated with growth rate, except the
      rate increase in fasting serum gastrin and the presence of bilobar liver or bone
      metastases. The growth rate was highly predictive of death from tumor.
      CONCLUSION: The growth rate of metastatic gastrinoma varies markedly in different
      patients and 26% demonstrate no growth. The growth rate needs to considered in
      the determination of when and in whom antitumor therapy is initiated, as well as
      in the assessment of response to tumoricidal therapies.

PMID- 9196159
TI  - Adjuvant chemotherapy in colorectal cancer with high-dose leucovorin and
      fluorouracil: impact on disease-free survival and overall survival.
AB  - PURPOSE: The rationale for using adjuvant chemotherapy in colorectal cancer is to
      achieve better disease control and thus reduce the high rates of tumor recurrence
      and mortality in patients who undergo curative surgery. The current literature,
      including relevant abstracts, on clinical trials of fluorouracil (5-FU) in
      combination with high-dose leucovorin as adjuvant chemotherapy for colorectal
      cancer is reviewed. The intent is not to present new data, but to present the
      reader with a broad perspective and larger patient experience on which to base
      well-reasoned treatment decisions. DESIGN: Published clinical trials and
      abstracts presented at the 1996 American Society of Clinical Oncology (ASCO)
      meeting that assessed 5-FU in combination with high-dose leucovorin as adjuvant
      chemotherapy for colorectal cancer were surveyed. End points of interest were
      disease-free survival (DFS), overall survival, and toxicity. RESULTS: In
      randomized trials that used high-dose leucovorin at doses that ranged from daily
      times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU, significant
      improvements in both DFS and overall survival were observed over surgery alone
      (control). In patients treated with high-dose leucovorin/5-FU, DFS rates ranged
      from 71% to 77% compared with control (58% to 64%). A similar trend was seen in
      overall survival, with a range of 75% to 84% compared with control (63% to 77%).
      Toxicities observed for high-dose leucovorin administered on a weekly or daily
      times-five schedule were diarrhea, stomatitis, myelosuppression, and nausea.
      CONCLUSION: Overall, the results of these randomized trials support the use of
      high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer
      follow-up studies are needed to compare the benefits of these different regimens
      in terms of survival and to characterize adverse effects, especially those that
      may not be immediately evident. Adjuvant therapy with high-dose leucovorin/5-FU
      is an effective regimen that is well tolerated by many patients with colorectal
      cancer.

PMID- 9196160
TI  - Sexual dysfunction in nonseminoma testicular cancer patients is related to
      chemotherapy-induced angiopathy.
AB  - PURPOSE: To establish the prevalence of sexual dysfunctions after different
      treatment modalities for nonseminomatous testicular germ cell tumor (NSTGCT) and
      to investigate whether treatment-induced angiopathy and neuropathy is related to
      sexual dysfunction. PATIENTS AND METHODS: A questionnaire assessing sexual
      dysfunction was sent to 255 NSTGCT survivors. Polychemotherapy (PCT) regimens
      (cisplatin, vinblastine, and bleomycin [PVB], vinblastine substituted by
      etoposide [BEP], or cisplatin substituted by carboplatin [CEB], etoposide
      combined with cisplatin [EP], or with ifosfamide and cisplatin [VIP] were
      compared regarding treatment-induced angiopathy and neuropathy. Sexual
      dysfunctions were related to Raynaud's phenomenon and acral paresthesia. RESULTS:
      Among the 215 responders, 56 (26%) had been treated by orchidectomy and
      surveillance, 42 (19.6%) by PCT, and 117 (54.4%) by PCT and resection of residual
      retroperitoneal tumor mass (RRRTM). Overall, loss of libido was reported by
      19.1%, decreased arousal by 11.2%, erectile dysfunction by 12.1%, decreased
      intensity of orgasm by 20%, and ejaculatory problems by 28%. Patients treated
      with PVB suffered more often from Raynaud's phenomenon compared with those
      treated with other regimens (40.4% v 29%; P < .05) and from paresthesia (31.6% v
      14.7%; P < .05). Patients with Raynaud's phenomenon had more often erectile
      dysfunction (28.8%) compared with those without (8.4%) (P < .05). CONCLUSION:
      Compared with orchidectomy alone, PCT, with or without RRRTM, induced more often
      posttreatment sexual dysfunction. Compared with other chemotherapeutic regimens,
      signs of angiopathy and neuropathy were most prevalent in those treated with PVB.
      Erectile dysfunction was related to the chemotherapy-induced Raynaud's phenomenon
      but not to acral paresthesia.

PMID- 9196161
TI  - Phase II randomized trial of gallium nitrate plus fluorouracil versus
      methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced
      transitional-cell carcinoma.
AB  - PURPOSE: A phase II randomized trial of gallium nitrate/fluorouracil (5-FU)
      versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC)
      was performed in poor-risk patients with advanced urothelial tract tumors. The
      efficacy and toxicity of these regimens were compared. Assessment of dose-intense
      M-VAC as salvage treatment in patients who failed to respond to the gallium
      nitrate/5-FU regimen was also performed. PATIENTS AND METHODS: Thirty-four
      patients who had not received prior systemic chemotherapy were randomized to
      either arm of the study. All patients had one or more clinical features
      predicting a low likelihood of durable complete response to standard
      chemotherapy, ie, weight loss, visceral metastases, and low performance status.
      Gallium nitrate and 5-FU were each administered by continuous 5-day infusions
      every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant
      human granulocyte colony-stimulating factor (rh-G-CSF). RESULTS: Two of 17
      patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response
      to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI,
      71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to
      respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line
      therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate
      and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up
      duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was
      associated with a greater incidence of neutropenia and thrombocytopenia.
      CONCLUSION: Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk
      patients (P < .0001). Despite the overall high response rate, the median survival
      for patients with M-VAC remained unsatisfactory. Similar survival distributions
      were observed for patients who received investigational therapy followed by
      cisplatin-based therapy and patients treated with initial cisplatin-based
      therapy.

PMID- 9196162
TI  - Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and
      neovascularization in patients with radically resected non-small-cell lung
      cancer.
AB  - PURPOSE: To assess the prognostic value of p53, bcl-2, bax, and
      neovascularization in radically resected non-small-cell lung cancer (NSCLC)
      patients. PATIENTS AND METHODS: Tumors from 116 patients were assessed by
      immunohistochemistry for expression of p53 (DO7 and PAb1081), bcl-2, and the
      quantification of microvessel density (CD-31). In addition, the expression of bax
      was assessed in 61 stage I tumors. The median levels of expression of each marker
      were used as cutoff points. RESULTS: p53 was not correlated to any patient or
      tumor characteristic, whereas bcl-2 showed higher expression in squamous cell
      carcinomas (P < .001). bax expression was significantly related with male sex (P
      = .006) and adenocarcinoma type (P = .0013). p53 status, assessed with one
      monoclonal antibody (MoAb), was not predictive for survival; however, the
      combination of staining results obtained with two MoAbs identified the DO7
      /PAb1801+ tumors as those with the worst prognosis. bcl-2 expression was
      associated with longer survival in stage I patients (P = .0169). The combined
      group expressing p53+(PAb1801)/bcl-2- had the worst survival in stage I patients
      (P = .034) and in the whole series in comparison with the other combinations of
      the two oncoproteins. bax expression alone had no influence on survival of stage
      I patients, but patients with bax+/bcl-2- tumors had the worst prognosis (P = .02
      in comparison with bax+/bcl-2+). Tumor neovascularization was not related with
      other factors, and patients with CD-31+ tumors had a shorter survival duration
      than those with CD-31- tumors only in stage II (P = .0283). By multivariate
      analysis including all patients, the presence of p53+/ bcl-2- tumor expression
      and large tumor diameter (> or = 4cm) were independent prognostic factors for
      shorter survival duration. For stage I, only the presence of bax+/ bcl-2- tumor
      expression had a significant negative influence on survival. CONCLUSION: The
      interaction and the regulation of new biologic markers, such as those involved in
      the apoptotic pathway, are complex. Combinations of the expression of several of
      them may give more valuable information than the study of just one. Prognostic
      influence of p53 staining varied depending on the choice of antibody and the
      combination of bcl-2- together with p53+ (PAb1801) or with bax+ had the worst
      influence on survival for patients with stage I NSCLC.

PMID- 9196163
TI  - Double-blind, multicenter, randomized trial to compare the effect of two doses of
      adrenocorticotropic hormone versus placebo in controlling delayed emesis after
      high-dose cisplatin in adult patients with cancer.
AB  - PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the
      efficacy of two different doses of the depot formulation of adrenocorticotropic
      hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND
      METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1,
      all patients received cisplatin (60 to 120 mg/m2) and a combination of
      dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis.
      On day 2 (24 hours after cisplatin administration), patients were randomized to
      receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one
      additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse
      effects were recorded daily for every 24-hour period from day 2 to day 6. In a
      subset of patients, serum cortisol levels were measured between 20 and 72 hours
      after cisplatin administration. RESULTS: One hundred fifty patients were
      assessable. Over the 5 days of the study, delayed vomiting occurred less
      frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated
      with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The
      greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3
      (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant
      differences were observed among the three arms. The severity of delayed emesis
      expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80,
      respectively (P = .002). Patients treated with the higher dose of ACTH had the
      least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion
      rapidly increased after ACTH injection, but was suppressed for approximately 44
      hours in the placebo group. Toxicity was mild and transient in all groups.
      CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and
      nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than
      one of 1 mg. Whether the activity of ACTH is mediated only by adrenal
      corticosteroids needs to be verified.

PMID- 9196164
TI  - Malignancy-associated microangiopathic hemolytic anemia.

PMID- 9196165
TI  - Pulmonary changes in patients with lymphoma who receive paclitaxel.

PMID- 9196166
TI  - Changing paradigms in the management of breast cancer.

PMID- 9196167
TI  - Development of a direct PCR assay for detection of the diphtheria toxin gene.
AB  - PCR has proved to be a reliable tool for the detection of the diphtheria toxin
      gene, tox, and its use has allowed for the rapid differentiation between
      toxigenic and nontoxigenic strains. In this study, this PCR was further
      developed, evaluated, and standardized to detect this gene directly from clinical
      specimens. Optimal conditions for collection, transport, and storage of the
      clinical specimens and isolation and purification of DNA from the clinical
      specimens were defined. With two sets of primers that detect the A and B subunits
      of the diphtheria toxin gene, sensitivity levels of 50 and 500 CFU/PCR mixture,
      respectively, were achieved. This PCR was evaluated with 162 clinical samples
      collected from patients with diphtheria and other upper respiratory tract
      infections, as well as from healthy individuals.

PMID- 9196168
TI  - A subtype-specific peptide-based enzyme immunoassay for detection of antibodies
      to the G protein of human respiratory syncytial virus is more sensitive than
      routine serological tests.
AB  - Peptides deduced from the central conserved region (residues 158 to 189) of
      protein G of human respiratory syncytial virus (HRSV) subtypes A and B were used
      as antigens in subtype-specific enzyme-linked immunosorbent assays (G-peptide
      ELISAs). These G-peptide ELISAs were compared with seven other serological assays
      to detect HRSV infection: ELISAs based on complete protein G, on fusion protein
      F, and on nucleoprotein N; a complement fixation assay; a virus neutralization
      test; and ELISAs for the detection of immunoglobulin A (IgA) or IgM antibodies
      specific for HRSV. In paired serum samples from patients with HRSV infection,
      more infections were diagnosed by the G-peptide ELISA (67%) than by all other
      serological tests combined (48%). Furthermore, for 16 of 18 patients (89%), the G
      peptide ELISAs were able to differentiate between antibodies against HRSV
      subtypes A and B. This study shows that peptides corresponding to the central
      conserved region of the attachment protein G of HRSV can successfully be used as
      antigens in immunoassays. The G-peptide ELISA appeared to be more sensitive than
      conventional tests for the detection of HRSV antibody titer rises.

PMID- 9196169
TI  - A reverse-type sandwich enzyme-linked immunosorbent assay for detecting
      antibodies to Borna disease virus.
AB  - To investigate whether there is an epidemiological correlation between Borna
      disease virus (BDV) infection and human neuropsychiatric diseases, we established
      a reverse-type sandwich enzyme-linked immunosorbent assay (RS-ELISA) for
      detecting specific antibodies to BDV. In this assay, microplate wells were coated
      dispersely with BDV p40 antigen, followed by the addition of test samples at a
      low dilution and then the biotinylated p40. A preformed complex of streptavidin
      and horseradish peroxidase-conjugated biotin and an enzyme substrate were used to
      measure the captured biotinylated p40. Theoretically, RS-ELISA should
      specifically detect anti-BDV antibodies without nonspecific signals; such signals
      possibly occur in conventional serological assays. Additionally, the RS-ELISA
      could be applied under the same protocols to test samples from a variety of
      animals. By using anti-BDV rat and rabbit sera, the assay was standardized so
      that it had high specificity and sensitivity. When we used the RS-ELISA to
      determine the presence of anti-BDV antibodies in plasma from 70 patients with
      chronic schizophrenia as well as 40 healthy individuals in the Tokyo area of
      Japan, no plasma sample was found to possess specific antibodies to BDV p40,
      indicating no association between BDV infection and the disease in our testing
      population. A negative reaction was also shown for the sera that had previously
      been judged to be seropositive for BDV by an immunofluorescence or immunoblot
      test. These findings suggested that false-positive cases of infection due to
      nonspecific reactions may be included in previous seroepidemiological information
      with regard to BDV.

PMID- 9196170
TI  - Detection of Mycoplasma pulmonis in cilia-associated respiratory bacillus
      isolates and in respiratory tracts of rats by nested PCR.
AB  - To improve the detection of Mycoplasma pulmonis contamination of isolates of
      cilia-associated respiratory (CAR) bacillus, we developed a nested PCR method
      using primers for 16S rRNA gene sequences. Of 140 samples of 16 different CAR
      bacillus isolates, 73 (52%) were inhibitory in the first PCR, as indicated by the
      absence of amplicons of the internal control, but only 11 of 140 (7.9%) were
      inhibitory in the second PCR. Of 27 samples known to contain M. pulmonis, only 12
      (44%) were positive in the first PCR, but 25 of 27 (93%) were positive in the
      second PCR. Nested PCR also detected M. pulmonis in 21 of 61 (34%) CAR bacillus
      samples from which M. pulmonis could not be cultured and identified 2 additional
      M. pulmonis-contaminated CAR bacillus isolates. Of 359 respiratory and
      reproductive tract lavage samples from rats and mice, 35 (9.8%) were inhibitory
      in the first PCR, but only 15 (4.2%) were inhibitory in the second PCR. Of 72
      lavage specimens from rats inoculated with an avirulent, poorly infective M.
      pulmonis strain, 14 (19%) were positive by nested PCR, but only 2 of 72 (2.8%)
      were positive by culture. Nested PCR also detected M. pulmonis in 14 of 20 (70%)
      paraffin sections of lung and trachea from rats and mice inoculated with CAR
      bacillus isolates known to contain M. pulmonis, whereas single PCR gave no
      positive results. We conclude that nested PCR is superior to single PCR or
      culture for detecting M. pulmonis, and that M. pulmonis is present in all but
      four CAR bacillus isolates in our collection that were from naturally infected
      rats; the four isolates that were exceptions were obtained from rats from a
      single colony.

PMID- 9196171
TI  - Identification of Aeromonas clinical isolates by restriction fragment length
      polymorphism of PCR-amplified 16S rRNA genes.
AB  - Identification of Aeromonas species, emergent pathogens for humans, has long been
      controversial due to their phenotypic and genomic heterogeneities. Computer
      analysis of the published 16S rRNA gene sequences revealed that restriction
      fragment length polymorphism of the PCR-amplified 16S rRNA gene is a good and
      rapid way of assessing the identities of all known species of Aeromonas. The
      method was evaluated with the reference strains of all species (or DNA homology
      groups) and 76 clinical isolates of diverse origin. Most results from the two
      approaches were in agreement, but some discrepancies were discerned. Advantages
      over previous phenotypic and genetic methods are discussed.

PMID- 9196172
TI  - Molecular typing of enterohemorrhagic Escherichia coli O157:H7 isolates in Japan
      by using pulsed-field gel electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) was applied for molecular typing of 825
      enterohemorrhagic Escherichia coli (EHEC) O157:H7 isolates, most of which were
      from 19 outbreaks and 608 sporadic cases in Japan, mainly in May to August 1996.
      By PFGE, the EHEC O157:H7 isolates were classified into six types (type I to V
      and ND [nondescript]) and UT untypeable isolates. Fifty isolates from seven
      outbreaks in May to June and 60 isolates from patients with sporadic cases of
      infection showed almost identical PFGE patterns which differed in only 1 of 22
      DNA fragments. They were classified into type I. Ninety-nine isolates from 10
      other outbreaks and 156 isolates from patients in the Kinki area with sporadic
      cases of infection obtained in the early summer of 1996 showed identical PFGE
      patterns, suggesting that they were derived from one huge outbreak. They were
      classified into type II. Type IV EHEC isolates, which had only the stx2 gene,
      caused another outbreak in a primary school in June. EHEC isolates of two other
      types, types III and V, were not related to the outbreak but were isolated in
      several parts of Japan. ND EHEC isolates included a variety of patterns which
      could not be classified into either of the types mentioned above. Twenty-five
      isolates could not be analyzed due to degradation of their genomic DNAs and were
      represented as UT. These results indicate that EHEC O157:H7 strains with various
      PFGE types have already spread to Japan and caused the multiple outbreaks and
      sporadic infections in Japan in the summer of 1996.

PMID- 9196173
TI  - Isolation of Ehrlichia chaffeensis from wild white-tailed deer (Odocoileus
      virginianus) confirms their role as natural reservoir hosts.
AB  - Field and experimental studies have implicated white-tailed deer (Odocoileus
      virginianus) as probable reservoir hosts for Ehrlichia chaffeensis, the causative
      agent of human monocytic ehrlichiosis, but natural infection in deer has not been
      confirmed through isolation of E. chaffeensis. Thirty-five white-tailed deer
      collected from three Amblyomma americanum-infested populations in Georgia were
      examined for evidence of E. chaffeensis infection by serologic, molecular, cell
      culture, and xenodiagnostic methods. Twenty-seven deer (77%) had E. chaffeensis
      reactive indirect fluorescent-antibody assay titers of > or = 1:64; and the
      blood, spleens, or lymph nodes of seven (20%) deer were positive in a nested PCR
      assay with E. chaffeensis-specific primers. E. chaffeensis was isolated in DH82
      cell cultures from the blood of five (14%) deer, including two deer that were PCR
      negative. Combination of culture and PCR results indicated that six (17%) deer
      were probably rickettsemic and that nine (26%) were probably infected.
      Restriction digestion of PCR products amplified from deer tissues and cell
      culture isolates resulted in a banding pattern consistent with the E. chaffeensis
      16S rRNA gene sequence. The sequences of all PCR products from deer tissues or
      cell culture isolates were identical to the sequence of the Arkansas type strain
      of E. chaffeensis. Xenodiagnosis with C3H mice inoculated intraperitoneally with
      deer blood, spleen, or lymph node suspensions was unsuccessful. When viewed in
      the context of previous studies, these findings provide strong evidence that E.
      chaffeensis is maintained in nature primarily by a tick vector-vertebrate
      reservoir system consisting of lone star ticks and white-tailed deer.

PMID- 9196174
TI  - Study of internal transcribed spacer and mitochondrial large-subunit genes of
      Pneumocystis carinii hominis isolated by repeated bronchoalveolar lavage from
      human immunodeficiency virus-infected patients during one or several episodes of
      pneumonia.
AB  - The objective of this study was to type, analyze, and compare Pneumocystis
      carinii hominis strains obtained from different samples during a given or
      recurrent episodes of P. carinii pneumonia (PCP) for epidemiologic purposes. We
      studied 36 bronchoalveolar lavage (BAL) or induced sputum (IS) samples from 16
      human immunodeficiency virus-infected patients with one or several episodes of
      PCP. PCR amplification and direct sequencing were performed on the two internal
      transcribed spacers (ITS1 and ITS2) of P. carinii hominis rRNA genes by using DNA
      extracted from BAL or IS samples, and the sequences were compared to the
      mitochondrial large-subunit (mt LSU) gene sequence determined in a previous study
      in our laboratory. The studies of the mt LSU and ITS sequences showed that some
      patients (n = 10) were infected with the same strains of P. carinii hominis
      during a given episode of PCP. In one patient infected with strains with
      identical sequences in several episodes, the recurrence could have been due to
      reactivation of organisms not eliminated by treatment during the first episode or
      to de novo infection by an identical strain. In five patients infected with
      strains with different sequences in each episode, recurrence was due to de novo
      infection. Sequence analysis of these two P. carinii hominis gene regions showed
      that de novo infection can occur in AIDS patients with recurrent PCP.

PMID- 9196175
TI  - Simplified sample processing combined with a sensitive one-tube nested PCR assay
      for detection of Pneumocystis carinii in respiratory specimens.
AB  - Early diagnosis of Pneumocystis carinii pneumonia, a life-threatening
      complication in immunosuppressed patients, may lower morbidity and mortality. We
      have developed a one-tube nested PCR assay for the detection of P. carinii in
      respiratory specimens. Four primers were selected from the sequence of the small
      subunit rRNA gene of P. carinii to amplify a 265-bp fragment, and their
      specificities for P. carinii were confirmed by both theoretical evaluations (by
      computer-assisted comparison with the sequences in GenBank) and empirical
      evaluations (with DNA from medically important fungi and diagnostic samples). The
      assay was optimized for routine diagnostic use. Processing of the clinical
      samples is rapid and simple (digestion with proteinase K directly in PCR buffer
      at room temperature in the presence of 10% Chelex 100 and no further purification
      steps). Bovine serum albumin (1 mg/ml) and glycerol (10%) in the amplification
      buffer reduced the number of samples inhibitory to the PCR, as assessed by
      control reactions containing a size-modified target. A total of 749 clinical
      specimens (312 bronchoalveolar lavage, 403 sputum or induced sputum, and 34 other
      specimens) from 507 patients (295 human immunodeficiency virus [HIV]-infected and
      164 non-HIV-infected patients and 48 patients whose HIV status was unknown) were
      tested by PCR, and the results were compared with those of an indirect
      immunofluorescence assay (IFA). Concordant results were obtained for 732 samples
      (646 negative and 86 positive). There were 17 discrepant results: 12 were PCR
      positive and IFA negative, and 5 were PCR negative and IFA positive. After
      resolution of the discrepant results by review of the patients' clinical data,
      the sensitivity and specificity were 94.8 and 99.1%, respectively, for PCR and
      93.8 and 100%, respectively, for IFA. In conclusion, the short procedure time and
      the technical ease of this PCR assay render it suitable for implementation in
      routine diagnostic laboratories.

PMID- 9196176
TI  - Development of a PCR assay for rapid diagnosis of Mycobacterium ulcerans
      infection.
AB  - The diagnosis of Mycobacterium ulcerans infection is hampered by the slow growth
      of the bacterium in culture, resulting in a delay of several months before a
      specific diagnosis can be obtained. In addition, M. ulcerans cannot be isolated
      from water even when there is convincing epidemiological evidence implicating
      this as the source of infection. The aim of the present study was to develop a
      PCR assay to circumvent the problems of delayed diagnosis and insensitivity of
      standard bacterial culture for M. ulcerans. For the PCR, we isolated an M.
      ulcerans-specific DNA fragment, 1,109 bp long, which is repeated at least 50
      times throughout the genome. Use of this sequence as a target for PCR allowed us
      to detect as few as 2 molecules of genomic DNA in vitro. The PCR was used to
      detect M. ulcerans DNA in fresh tissue and paraffin-embedded sections from all
      seven patients with culture-confirmed cases of infection.

PMID- 9196177
TI  - Simple differential detection of Entamoeba histolytica and Entamoeba dispar in
      fresh stool specimens by sodium acetate-acetic acid-formalin concentration and
      PCR.
AB  - Amoebiasis is caused by two distinct species, a pathogenic form (Entamoeba
      histolytica) and a nonpathogenic form (Entamoeba dispar), which are
      morphologically identical. Although the distinction between these two species is
      of great clinical importance, the methods developed for this purpose either are
      very time-consuming or involve laborious procedures for isolation of the DNA. We
      report here a simple PCR method starting with fresh stool specimen that allows
      for the sensitive and reliable distinction between E. histolytica and E. dispar.
      After initial concentration by the sodium acetate-acetic acid-formalin (SAF)
      method and digestion with proteinase K, a 0.88-kb sequence of the multicopy 16S
      rRNA gene served as a target for PCR amplification. The method starting with
      unpreserved specimens proved to be very sensitive and was not influenced by the
      quick exposure to SAF fixative during the initial concentration step. However,
      storage in SAF fixative prior to testing resulted in a decreased sensitivity
      within 2 days. The detection limit of the method was as low as one copy of the
      16S rRNA gene. No cross-reactivity was observed with other common intestinal
      protozoa. Mixed infections involving both E. histolytica and E. dispar could
      easily be detected at a ratio of 1:10,000 by agarose gel electrophoresis or a DNA
      hybridization immunoassay.

PMID- 9196178
TI  - The first clinical isolate of Legionella parisiensis, from a liver transplant
      patient with pneumonia.
AB  - A bluish white autofluorescent strain of Legionella was isolated from the
      tracheal aspirate of a female liver transplant patient who developed hospital
      acquired pneumonia. This strain had biochemical characteristics compatible with
      those of L. cherrii, L. anisa, and L. parisiensis and could not be differentiated
      from L. bozemanii and L. parisiensis by the direct fluorescent-antibody assay.
      Phylogenetic analysis of partial 16S rRNA gene sequences of this strain (ATCC
      700174) revealed the closest homology to the species L. parisiensis (99.5%). An
      L. parisiensis species-specific profile was also identified by a random amplified
      polymorphic DNA technique. This is the first report of L. parisiensis isolation
      from humans.

PMID- 9196179
TI  - Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter
      pylori isolated in Japan.
AB  - Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is
      encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in
      vacA alleles was reported, and there are three different families of vacA signal
      sequences (s1a, s1b, and s2) and two different families of middle-region alleles
      (m1 and m2). In addition, the vacA genotype of a strain is associated with its
      cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the
      strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H.
      pylori (40 from patients with chronic atrophic gastritis, 25 from patients with
      duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both
      duodenal and gastric ulcers, and 3 from patients with intestinal type gastric
      cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four
      of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed.
      Moreover, all isolates in this study were cagA positive. There were no distinct
      differences between the cytotoxin-producing strains and cytotoxin-nonproducing
      strains within the 0.73-kb middle region. Japanese strains were highly
      homologous, with more than 96% identity in this region, in which maximum
      divergence has been reported. In addition, there were no associations between the
      specific vacA types and the level of in vitro cytotoxin activity or the clinical
      consequences. These results indicate that the cagA-positive, s1a/m1-type strains
      are common in Japan, regardless of the vacA phenotype or clinical outcome.

PMID- 9196181
TI  - Potential for gene transfer among enterococci from a single patient and the
      possibility of confounding typing results.
AB  - The results of typing methods used in a study of the epidemiology of enterococci
      in burn patients showed inconsistencies. The possibility that these
      inconsistencies were the result of gene acquisition or loss was investigated by
      using 12 isolates of Enterococcus faecalis from a single patient. In vivo and in
      vitro exchange and loss of genes were observed. The study showed that the typing
      results for isolates from this patient can be modified by known and demonstrated
      genetic elements; as a result, the isolates could be divided into between three
      and seven strains. In the present study, the SmaI digestion patterns gave the
      most consistent results, correctly identifying the transconjugants as
      indistinguishable from recipient strain 196R.

PMID- 9196180
TI  - Production of monoclonal antibodies against Rickettsia massiliae and their use in
      antigenic and epidemiological studies.
AB  - Rickettsiae are gram-negative, obligate intracellular bacteria which have
      historically been divided into three groups: the typhus group, the scrub typhus
      group, and the spotted fever group (SFG). Recently, several new SFG rickettsiae
      have been characterized, and most of these species are associated with ticks and
      have, as yet, no known pathogenicity toward humans. Rickettsia massiliae, which
      is widely distributed in Europe and Africa, is one such rickettsia. In order to
      investigate the antigenic relationships between R. massiliae and other
      rickettsial species and to develop a more convenient methodology for identifying
      R. massiliae, we produced monoclonal antibodies against the type strain (Mtu1T)
      of R. massiliae by fusing immunized splenocytes with SP2/0-Ag14 myeloma cells. A
      panel of 16 representatives were selected from the 163 positive hybridomas
      identified on initial screening, and their secreted monoclonal antibodies were
      further characterized. The reactivities of these 16 monoclonal antibodies with a
      large panel of rickettsial species were assessed by the microimmunofluorescence
      assay. All species of the SFG rickettsiae reacted with the monoclonal antibodies
      directed against epitopes on lipopolysaccharide, which is the common antigen
      among the SFG rickettsiae. Some closely related species of the SFG, such as
      Bar29, "R. aeschlimanni," and R. rhipicephali, showed strong cross-reactivities
      with the monoclonal antibodies directed against epitopes on the two major high
      molecular-mass heat-labile proteins (106 and 120 kDa). In addition, species
      specific monoclonal antibodies demonstrated that R. massiliae is antigenically
      different from other rickettsial species. Moreover, these species-specific
      monoclonal antibodies were successfully used for identifying R. massiliae in the
      ticks collected from southern France, and are therefore potentially useful tools
      in the identification and investigation of R. massiliae in ticks in large-scale
      field work.

PMID- 9196182
TI  - Use of cloned excretory/secretory low-molecular-weight proteins of Cooperia
      oncophora in a serological assay.
AB  - The potential of Cooperia oncophora excretory/secretory (ES) proteins as antigens
      in a serological assay which aims to establish exposure levels in cattle was
      assessed. ES proteins were analyzed by one- and two-dimensional polyacrylamide
      gel electrophoresis and immunoblotting. The N-terminal domains of two ES proteins
      were sequenced, and the corresponding cDNAs were cloned. Two cDNAs, designated
      CoES14.0 and CoES14.2, were expressed in Escherichia coli. The recombinant
      proteins were tested in an indirect enzyme-linked immunosorbent assay (ELISA) in
      which crude worm antigen (CWA) was used as a reference standard. In total, 67
      reference serum samples were used: 27 negative serum samples, 29 C. oncophora
      specific serum samples, 7 Dictyocaulus viviparus-specific serum samples, and 4
      Ostertagia ostertagi-specific serum samples. This showed respective sensitivities
      and specificities of 17 and 84%, 0 and 100%, and 100 and 100% by the ELISAs with
      the three different types of proteins (CWA, CoES14.0, and CoES14.2,
      respectively). Since the CoES14.2 ELISA had the best sensitivity and specificity
      with reference sera, its specificity was further validated in an antigen
      inhibition ELISA. In this assay CoES14.2 and CWA preparations of C. oncophora,
      Cooperia curticei, O. ostertagi, Nematodirus helvetianus, Fasciola hepatica, D.
      viviparus, Haemonchus placei, and Trichostrongylus colubriformus were used as
      competitor antigens. This experiment showed that only the homologous antigens C.
      oncophora CWA and CoEs14.2 resulted in 100% inhibition. The CWA preparations of
      all other nematodes did not affect the ELISA, even if concentrations of 250 times
      the 50% inhibitory concentration of C. oncophora CWA were used. These results
      indicate that CoES14.2 does not share cross-reactive epitopes with heterologous
      CWAs. Finally, we tested the CoES14.2 ELISA with sequential serum samples from
      naturally infected groups of animals. The optical density values that were
      obtained correlated well with exposure levels based on cumulative egg excretion.
      Thus, the CoES14.2 ELISA seems to be a very sensitive tool for estimating
      exposure levels in cattle.

PMID- 9196183
TI  - Serological determination of hepatitis C virus genotype: comparison with a
      standardized genotyping assay.
AB  - In patients with chronic hepatitis C, determination of hepatitis C virus (HCV)
      genotype could be routinely run in the future to tailor treatment schedules. The
      suitabilities of two versions of a serological, so-called serotyping assay (Murex
      HCV Serotyping Assay version 1-3 [SA1-3] and Murex HCV Serotyping Assay version 1
      6 [SA1-6]; Murex Diagnostics Ltd.), based on the detection of genotype-specific
      antibodies directed to epitopes encoded by the NS4 region of the genome, for the
      routine determination of HCV genotypes were studied. The results were compared
      with those of a molecular biology-based genotyping method (HCV Line Probe Assay
      [INNO-LiPA HCV]; Innogenetics S.A.), based on hybridization of PCR products onto
      genotype-specific probes designed in the 5' noncoding region of the genome,
      obtained with pretreatment serum samples from 88 patients with chronic hepatitis
      C eligible for interferon therapy. Definitive genotyping was performed by
      sequence analysis of three regions of the viral genome in all samples with
      discrepant typing results found among at least two of the three assays studied.
      In all instances, sequence analysis confirmed the result of the INNO-LiPA HCV
      test. The sensitivity of SA1-3 was 75% relative to the results obtained by the
      genotyping assay. The results were concordant with those of genotyping for 92% of
      the samples typeable by SA1-3. The sensitivity of SA1-6 was 89% relative to the
      results obtained by the genotyping assay. The results were concordant with those
      of genotyping for 94% of the samples typeable by SA1-6. Overall, SA1-6 had
      increased sensitivity relative to SA1-3 but remained less sensitive than the
      genotyping assay on the basis of PCR amplification of HCV RNA. Cross-reactivities
      between different HCV genotypes could be responsible for the mistyping of 8 (SA1
      3) and 6% (SA1-6) of the samples. Subtyping of 1a and 1b is still not possible
      with the existing peptides, but discriminating between subtypes may not be
      necessary for routine use.

PMID- 9196184
TI  - Detection of Neospora from tissues of experimentally infected rhesus macaques by
      PCR and specific DNA probe hybridization.
AB  - Neospora is a newly recognized Toxoplasma-like cyst-forming coccidian parasite
      that causes abortion or congenital infections in naturally or experimentally
      infected animals. In this study, pregnant rhesus macaques were inoculated with
      culture-derived tachyzoites of a bovine Neospora isolate, and tissue samples from
      various major organs were collected from dams and fetuses for the detection of
      parasite DNA by using oligonucleotide primers COC-1 and COC-2 for PCR
      amplification of a conserved coccidial nuclear small-subunit rRNA gene sequence,
      and amplification products were confirmed by hybridization with a Neospora
      specific DNA probe. PCR products were amplified from DNAs of different fetal
      monkey tissues, including brain, heart, lung, liver, spleen, skeletal muscle,
      skin, and placenta. In addition, Neospora DNA was amplified from the brain,
      heart, and lung tissues of infected rhesus macaque dams. The PCR and probe
      hybridization system may provide an effective method for the detection of
      Neospora infection in fetuses and dams from nonhuman primates and may be useful
      in determining the zoonotic potential of Neospora.

PMID- 9196185
TI  - An epidemiological study of blood culture isolates of coagulase-negative
      staphylococci demonstrating hospital-acquired infection.
AB  - We applied pulsed-field gel electrophoresis (PFGE) after SmaI digestion and
      random amplification of polymorphic DNA (RAPD) analysis with nine oligonucleotide
      primers to 146 blood culture isolates of Staphylococcus epidermidis and 25 blood
      culture isolates of Staphylococcus haemolyticus. These were obtained over a 12
      month period from patients on the neonatal and hematology units of the Central
      Manchester Health Care Trust. PFGE demonstrated two clusters of isolates of S.
      epidermidis (type A and type B) on the neonatal ward and a single cluster (type
      C) on the hematology unit. Type A was represented by 10 indistinguishable
      isolates from nine patients, type B was represented by 20 isolates from 14
      patients, and type C was represented by 26 isolates from 10 patients. Type A
      isolates were resistant to chloramphenicol and type C isolates were resistant to
      ciprofloxacin, mirroring current antibiotic usage. There was no evidence of cross
      infection due to S. haemolyticus. RAPD analysis, on the basis of a single band
      difference, produced 58 types of S. epidermidis and 12 types of S. haemolyticus
      with primer 8 (ATG TAA GCT CCT GGG GAT TCA C; 5' to 3') and 54 types of S.
      epidermidis and 10 types of S. haemolyticus with primer 9 (AAG TAA GTG ACT GGG
      GTG AGC G; 5' to 3'). Combining the results confirmed cross infection. Types A,
      B, and C were concurrently isolated from the hands of the staff of the
      appropriate unit. Partial control was achieved by withdrawing ciprofloxacin use
      in the case of the hematology unit and improving hand hygiene in both units.

PMID- 9196186
TI  - Interlaboratory agreement among results of human papillomavirus type 16 enzyme
      linked immunosorbent assays.
AB  - Serological assays for measuring antibodies to human papillomavirus type 16 (HPV
      16) virus-like particles (VLPs) have become important epidemiologic tools in
      recent years. However, the interlaboratory replicability of these assays has not
      been assessed. In this investigation, three laboratories tested a panel of
      specimens obtained from two different groups: 265 subjects in a vulvar cancer
      case-control study and 107 healthy volunteer blood donors. Each laboratory used
      an enzyme-linked immunosorbent assay (ELISA), but no attempt was made to
      standardize assay procedures among the three laboratories. The data showed good
      day-to-day intralaboratory replicability in laboratory 1 (correlation
      coefficient, > or = 0.88) and good intra-assay variability in laboratory 3
      (correlation coefficient, > or = 0.93). Interlaboratory correlations, likewise,
      ranged between 0.61 and 0.80 in both case-control study subjects and healthy
      blood donors, indicating that ELISA optical density (OD) values between
      laboratories were linearly related regardless of the population. Kappa
      coefficients (kappa), based on each laboratory's categorical interpretation of
      its results (as positive or negative), showed good agreement (kappa, > 0.6) in
      case-control study subjects and moderate agreement (kappa, > or = 0.4) in blood
      donors, a population that had few strongly positive sera. When OD values near
      seropositive cutoffs were treated as indeterminates, there was little discordance
      between laboratories in either population. The data suggest that each laboratory
      measured the same humoral immune response and that their HPV-16 VLP ELISAs
      performed similarly (Pearson correlations). Interlaboratory differences, however,
      probably due to reagents and procedures, were considerably greater than
      intralaboratory day-to-day variability. Interlaboratory agreement in determining
      seropositivity (kappa) could be improved by sharing positive and negative serum
      controls and by treating marginal results as indeterminate. As part of continuing
      cooperation to improve interlaboratory agreement, we are preparing bulk serum
      control specimens to be shared and made available to interested researchers.

PMID- 9196187
TI  - Identification of enteroinvasive Escherichia coli and Shigella strains in
      pediatric patients by an IpaC-specific enzyme-linked immunosorbent assay.
AB  - A new method, a monoclonal antibody-based enzyme-linked immunosorbent assay
      (ELISA) recognizing a secreted, invasion plasmid-coded protein antigen (IpaC),
      was used to identify enteroinvasive Escherichia coli and Shigella strains among
      colonies from 859 cultures of fecal samples from children in Kuwait. A total of
      33.8% of the samples were diarrheal. By the immunoassay, enteroinvasive E. coli
      strains were identified from two diarrheal samples but from none of the samples
      from children without diarrhea. These strains were fully virulent and belonged to
      serogroup O28ac. In addition, 26 Shigella strains were also recognized by the
      ELISA, while only 23 were isolated by routine biotyping and serotyping. For two
      diarrheal patients, Shigella was identified by culture only. The study showed
      that the IpaC-specific immunoassay is a simple and useful tool for identifying
      enteroinvasive strains. Furthermore, by reporting the first enteroinvasive E.
      coli isolates from Kuwait, the study indicates the presence of this group of
      pathogens as a potential source of diarrhea in the region.

PMID- 9196188
TI  - Variations in fluconazole susceptibility and DNA subtyping of multiple Candida
      albicans colonies from patients with AIDS and oral candidiasis suffering one or
      more episodes of infection.
AB  - Five Candida albicans colonies from each infection in AIDS patients receiving
      fluconazole therapy for oropharyngeal candidiasis over a 2-year period were
      evaluated by antifungal susceptibility testing and DNA subtyping, and the results
      were correlated with clinical response to determine the occurrence of clinically
      significant selection of more-resistant C. albicans over multiple infections. A
      total of 534 C. albicans isolates were obtained from 38 patients who exhibited 84
      episodes of infection. Antifungal susceptibility testing revealed that the MICs
      for 93% of the isolates were < or = 8.0 microg/ml and the MICs for 7% of the
      isolates were > or = 64 microg/ml. DNA subtyping revealed 70 different subtypes,
      with 78% of patients with one infection exhibiting one DNA subtype and 80% of
      patients with more than one infection exhibiting multiple DNA subtypes. Also,
      patients who had multiple infections had lower CD4 counts than those with single
      infections. Differences between the single-infection group and the multiple
      infection group regarding the number of DNA subtypes and CD4 counts were both
      statistically significant. Of the 74 evaluable infections all were successfully
      treated with regular-dose (100-mg/day) fluconazole, except for three patients who
      ultimately responded to higher-dose fluconazole. Only one patient may have shown
      clinically significant selection of a more-resistant C. albicans strain over
      multiple courses of treatment. Interestingly, MICs reached only 8.0 microg/ml,
      even though doses of 400 mg of fluconazole were necessary for clinical cure.

PMID- 9196189
TI  - Differentiation of primary from nonprimary genital herpes infections by a herpes
      simplex virus-specific immunoglobulin G avidity assay.
AB  - An immunoglobulin G (IgG) antibody avidity assay which uses protein-denaturing
      agents and a modification of an enzyme-linked immunosorbent assay have been
      investigated for their usefulness in distinguishing primary genital herpes
      simplex virus (HSV) infections from nonprimary infections. Forty-nine serum
      specimens from patients with primary, recurrent, and nonprimary first-episode
      genital herpes were studied. The clearest separation was obtained with 6 M urea
      treatment, giving mean avidity indices of 0.398 for sera < or = 100 days after
      the infection and 0.879 for sera > 100 days after the infection (P < 0.001). No
      significant difference in avidity indices was observed between the recurrent and
      nonprimary first-episode infections. Determination of the avidity of HSV-specific
      IgG will improve the diagnostic potential of HSV serology.

PMID- 9196190
TI  - IS6110 homologs are present in multiple copies in mycobacteria other than
      tuberculosis-causing mycobacteria.
AB  - We have previously demonstrated homology between a 181-bp fragment of IS6110 and
      DNA from mycobacteria other than tuberculosis-causing mycobacteria (MOTT).
      Genomic DNA from 14 strains of MOTT was digested with PvuII and was hybridized
      with a probe derived from the 181-bp fragment and the INS1/INS2 international
      standard probe at high stringency. Multiple banding patterns were obtained from
      isolates of M. avium-M. intracellulare, M. fortuitum, M. kansasii, and M.
      malmoense. Differences in the banding patterns between and within species were
      obtained. This suggests that mycobacteria possess a family of IS3-like elements.
      The species of isolates suspected of being M. tuberculosis must be carefully
      determined before IS6110 restriction fragment length polymorphism analysis, and
      caution must be used in designing and evaluating diagnostic PCR tests based on
      this element.

PMID- 9196191
TI  - Genotypic distribution of hepatitis C virus in different regions of Thailand.
AB  - The genotypic distribution of hepatitis C virus (HCV) isolated from blood donors
      from four major regions of Thailand was studied by reverse hybridization assays.
      PCR-amplified products from the 5' noncoding and core regions of the viral genome
      were hybridized to genotype- and subtype-specific probes which were immobilized
      on the nitrocellulose membrane. Of 332 anti-HCV-positive plasma samples studied,
      71% contained HCV RNA. HCV genotype 3a was the most prevalent genotype (39%),
      followed by genotype 1b (20%) and genotype 6 group variants (18%). HCV genotype
      1a was identified among 9% of all isolates. Other genotypes (genotype 1 which was
      neither 1a nor 1b, genotype 3b, and an unclassified genotype) were uncommon.
      There was no difference in the mean age of the donors infected with different HCV
      genotypes. The genotypic distribution pattern of HCV was similar among HCV
      isolates from different regions of Thailand.

PMID- 9196193
TI  - Detection of endocervical anti-Chlamydia trachomatis immunoglobulin A in pregnant
      women by a rapid, 6-minute enzyme-linked immunosorbent assay: comparison with PCR
      and chlamydial antigen detection methods.
AB  - There is a need for a rapid, uncomplicated, and inexpensive test for Chlamydia
      trachomatis infection in women. We evaluated the ability of a 6-min enzyme-linked
      immunosorbent assay (ELISA) that requires no laboratory equipment (IgA Rapid
      SeroTest; Savyon Diagnostics) to detect C. trachomatis immunoglobulin A (IgA) in
      the endocervices of 167 inner-city pregnant women and compared the results with
      DNA amplification (Amplicor PCR; Roche Diagnostics) and antigen detection
      (Chlamydiazyme; Abbott Laboratories) performed on the same women. Anti-C.
      trachomatis IgA was detected in the cervices of 32 women (19.2%). Samples from 23
      women (13.8%) were PCR positive, while chlamydial antigen was present in 20 women
      (12.0%). There was only 1 sample (4.3%) that was positive by PCR but negative by
      ELISA; 10 samples were ELISA positive and PCR negative. In contrast, seven
      samples (30.4%) were PCR positive but Chlamydiazyme negative and four were
      Chlamydiazyme positive and PCR negative. Compared to PCR, the IgA ELISA had a
      sensitivity of 95.7%, a specificity of 93.1%, a positive predictive value of
      68.8%, and a negative predictive value of 99.3%. The antigen assay had a
      sensitivity of only 69.6%, a specificity of 97.2%, a positive predictive value of
      80.0%, and a negative predictive value of 95.2%. In high-risk groups where
      laboratory testing is not available, or where the patient might not return to
      obtain her testing result and be treated, the Rapid IgA SeroTest is a viable
      alternative for detection of cervical C. trachomatis in pregnant women.

PMID- 9196192
TI  - Microsatellite polymorphism in the promoter sequence of the elongation factor 3
      gene of Candida albicans as the basis for a typing system.
AB  - The polymorphism of a TTC/TTTC microsatellite in the promoter sequence of the
      elongation factor 3 gene of Candida albicans was investigated by PCR. One primer
      was fluorescein labeled, and PCR signals were read with an automatic sequencer.
      Twenty-nine reference strains and 31 independent clinical isolates were studied.
      Eleven different alleles were identified, giving 16 different profiles among the
      60 strains tested, with a discriminatory power of 0.88. This marker is stable
      upon subculture, and reproducibility was achieved by automated procedures. When
      several microsatellite markers are available, many isolates can be rapidly and
      reproducibly tested for epidemiological questions, such as the prevalence of a
      given strain in a hospital setting and transmission between patients.

PMID- 9196194
TI  - Serial surveillance cultures of skin and catheter hub specimens from critically
      ill patients with central venous catheters: molecular epidemiology of infection
      and implications for clinical management and research.
AB  - A prospective study of 45 central venous catheters was conducted to assess, by
      strain delineation, the turnover of skin and catheter hub (superficial)
      colonization and the relative contributions of catheter hub and skin colonization
      to catheter tip colonization. Serial quantitative cultures of skin and catheter
      hub were performed. Catheter tip, blood, and specimens for culture from targeted
      superficial sites (TSSs) were also collected at the time of catheter removal.
      Strains from 17 tip-positive catheters were delineated by pulsed-field gel
      electrophoresis. Only 12 (28.6%) of 42 skin strains and 14 (31.1%) of 45 catheter
      hub strains were found to be present at the time of catheter removal. In
      addition, only 9 (29.0%) of the 31 tip-colonizing strains were present on TSSs.
      Moreover, 15 (48.4%) of the 31 tip-colonizing strains had a superficial origin,
      and the other 16 (51.6%) were of unknown origin. In catheters suspected of
      infection, cultures of TSSs had a negative predictive value for catheter-related
      bacteremia of 94.4% but a positive predictive value of 44.4%. When the causative
      agent was identified (to the strain level) these values dropped to 80.9 and
      18.7%, respectively. The study shows that skin and catheter hub colonization is a
      common, dynamic phenomenon. Strains recovered from TSSs showed a low level of
      correlation with strains from previous cultures of specimens from superficial
      sites and catheter tip isolates. Consequently, TSSs cannot be recommended for use
      in determining the therapy. However, catheter-related bacteremia is uncommon when
      cultures of TSSs are negative.

PMID- 9196195
TI  - Detection of rhinovirus in sinus brushings of patients with acute community
      acquired sinusitis by reverse transcription-PCR.
AB  - Of 20 adults with acute community-acquired sinusitis (ACAS), rhinovirus was
      detected in specimens from 10 (50%) patients, including maxillary aspirates from
      8 (40%) patients and nasal swabs from 9 (45%) patients, by reverse transcription
      PCR (RT-PCR). Human coronavirus was detected by RT-PCR in nasal swabs from 3 of
      20 patients but in no sinus secretions. These findings suggest that rhinovirus is
      an important cause of ACAS and that viral invasion of the sinus cavity itself may
      be a common event during the disease.

PMID- 9196196
TI  - Characterization of a specific Mycobacterium paratuberculosis recombinant clone
      expressing 35,000-molecular-weight antigen and reactivity with sera from animals
      with clinical and subclinical Johne's disease.
AB  - Johne's disease is a chronic enteritis of ruminants associated with enormous
      worldwide economic losses for the dairy cow- and goat-rearing industries.
      Management limitations and eradication programs for this disease have been
      hampered by the lack of a simple and specific diagnostic test for the detection
      of subclinical cases. We used a recombinant clone expressing a 35,000-molecular
      weight Mycobacterium paratuberculosis antigen (p35 antigen) from a previously
      constructed expression library of M. paratuberculosis in Escherichia coli. The
      DNA fragment encoding the p35 gene hybridized only to DNA from Mycobacterium
      avium complex, but not to DNAs from other mycobacteria and nonmycobacterial
      organisms. The seroreactivity of p35 was evaluated by immunoblotting against 57
      reference serum samples obtained from infected and uninfected animals. p35 was
      recognized by sera from 100% of animals with advanced Johne's disease (clinical
      stage) (12 cattle, 2 goats, and 2 sheep) and by sera from 75% of 20 cattle with
      early infection (subclinical stage). None of the sera from 15 M. paratuberculosis
      free cows, 3 Mycobacterium bovis BCG-infected tuberculous cattle, or 3 cows
      artificially inoculated with multiple doses of viable M. paratuberculosis reacted
      with p35. The overall sensitivity, specificity, positive predictive value, and
      negative predictive value were 86, 100, 100, and 75%, respectively. The accuracy
      of p35 immunoblotting was superior to those of commercially available diagnostic
      tests for Johne's disease. These results suggest that the p35 recombinant protein
      has potential for use in the serodiagnosis of animals with Johne's disease at all
      stages of infection. The DNA fragment encoding p35 may also serve as a probe for
      identification of M. avium complex infection.

PMID- 9196197
TI  - The role of arbitrarily primed PCR in identifying the source of an outbreak of
      Legionnaires' disease.
AB  - An outbreak of community-acquired Legionnaires' disease (LD) occurred in
      Providence, R.I., in fall 1993. To find the outbreak source, exposures of 17 case
      patients were compared to those of 33 matched controls. Case patients were more
      likely than controls to have visited a section of downtown (area A) during the 2
      weeks before illness (11 [65%] versus 9 [27%]; matched odds ratio, 6.5; P =
      0.01). Water samples were cultured from 27 aerosol-producing devices within area
      A. Legionella pneumophila serogroup 1 isolates underwent monoclonal antibody
      (MAb) subtyping and arbitrarily primed PCR (AP-PCR). All four L. pneumophila
      serogroup 1 isolates available from case patients who visited area A had
      identical MAb and AP-PCR patterns. Among 14 environmental isolates, 5 had MAb
      patterns that matched the case patient isolates, but only 1 had a matching AP-PCR
      pattern. This investigation implicates a cooling tower in area A as the outbreak
      source and illustrates the usefulness of AP-PCR for identifying sources of LD
      outbreaks.

PMID- 9196198
TI  - Bacteremia caused by a recently described novel Desulfovibrio species.
AB  - An obligately anaerobic, fastidious, slowly growing, spiral, gram-negative
      bacterium was isolated from the blood of a 75-year-old man with acute onset of
      pyrexia. The patient responded rapidly to appropriate antibiotic therapy.
      Extensive investigation failed to detect a focus for the infection.
      Phenotypically, the organism was consistent with Desulfovibrio species.
      Microscopic investigation revealed an organism with a vibrioid or spirillioid
      morphology with rapidly progressive motility by means of a single polar
      flagellum. Biochemically, the organism produced large amounts of H2S and
      contained desulfovirdin. The 16S rRNA gene sequence of the organism was found to
      be most similar to those of members of the genus Desulfovibrio, with identical
      sequence homology to the newly proposed species described by Tee et al. (W. Tee,
      M. Dyall-Smith, W. Woods, and D. Eisen, J. Clin. Microbiol. 34:1760-1764, 1996).
      This is a second unrelated isolation of this novel species from two widely
      different locations in Australia. The two isolates show some phenotypic
      differences, indicating that they are different strains of the same species.

PMID- 9196199
TI  - PCR-single-stranded confirmational polymorphism analysis for non-culture-based
      subtyping of meningococcal strains in clinical specimens.
AB  - Subspecific typing of clinical meningococcal strains is important in the
      investigation of outbreaks and for disease surveillance. Serogrouping, typing,
      and subtyping of strains currently require isolation of a meningococcus from one
      or more clinical specimens. However, the increasing widespread practice of
      preadmission administration of parenteral antibiotics has resulted in a decrease
      in the frequency of positive cultures obtained from blood and cerebrospinal
      fluid. Confirmation of meningococcal disease can be obtained by meningococcus
      specific PCR from both cerebrospinal fluid (H. Ni et al., Lancet 340:1432-1434,
      1992) and peripheral blood (J. Newcombe et al., J. Clin. Microbiol. 34:1637-1640,
      1996) specimens. However, current PCR protocols do not yield epidemiologically
      useful typing information. We report here the use of PCR-single-stranded
      confirmational polymorphism (PCR-SSCP) analysis to amplify and type meningococcal
      DNA present in clinical specimens. PCR-SSCP analysis with the VR1 region of the
      Neisseria meningitidis porA gene as the target produced unique banding patterns
      for each serosubtype. Direct PCR-SSCP of clinical specimens can therefore provide
      typing data that can be used to investigate the epidemiology of clusters of cases
      and outbreaks and for disease surveillance in situations in which culture of
      patient specimens proves negative.

PMID- 9196200
TI  - Bartonella clarridgeiae, a newly recognized zoonotic pathogen causing inoculation
      papules, fever, and lymphadenopathy (cat scratch disease).
AB  - Shortly after adopting a 6-week-old cat, a veterinarian was bitten on the left
      index finger. Within 3 weeks, he developed headache, fever, and left axillary
      lymphadenopathy. Initial blood cultures from the cat and veterinarian were
      sterile. Repeat cultures from the cat grew Bartonella-like organisms with
      lophotrichous flagella. Sera from the veterinarian were not reactive against
      Bartonella henselae, B. quintana, or B. elizabethae antigens but were
      seroreactive (reciprocal titer, 1,024) against the feline isolate. Sequential
      serum samples from the cat were reactive against antigens of B. henselae (titer,
      1,024), B. quintana (titer, 128), and the feline isolate (titer, 2,048).
      Phenotypic and genotypic characterization of this and six additional feline
      isolates, including microscopic evaluation, biochemical analysis, 16S rRNA gene
      sequencing, DNA-DNA hybridization, and PCR-restriction fragment length
      polymorphism of the 16S gene, 16S-23S intergenic spacer region, and citrate
      synthase gene identified the isolates as B. clarridgeiae. This is the first
      report of cat scratch disease associated with B. clarridgeiae.

PMID- 9196201
TI  - Comparison of culture and the antigenemia assay for detection of cytomegalovirus
      in blood specimens submitted to a reference laboratory.
AB  - We compared the antigenemia assay (AA) with tandem shell vial cultures (SVCs) and
      tube cultures (TCs) for detection of cytomegalovirus (CMV) in 343 blood
      specimens. For 249 specimens, the AA was performed in duplicate with two
      different commercially available monoclonal antibody reagents (Biotest Diagnostic
      Corporation and Argene Biosoft). Specimens considered true positives were
      positive in either culture system or both AAs. Only specimens which were negative
      in both cultures and positive in a single AA were tested retrospectively with a
      CMV PCR assay. CMV recovery rates were also calculated to determine if increased
      specimen age resulted in decreased positivity. CMV recovery rates for the AA and
      the combination of both cultures were 20.0 and 5.0% at 3 to 18 h, 20.2 and 14.0%
      at 18 to 35 h, 12.5 and 7.8% at 36 to 52 h, and 18.8 and 6.3% at 64 to 75 h,
      respectively. The sensitivities and specificities of the Biotest AA, the Argene
      AA, SVC, and TC were 84.4 and 100.0, 100.0 and 99.6, 44.4 and 100.0, and 46.0 and
      100.0%, respectively. The AA was significantly more sensitive than either culture
      method alone and was also more sensitive than the two culture methods used in
      tandem (the tandem culture sensitivity was 63.5%); the Argene AA identified more
      positives than the Biotest AA.

PMID- 9196202
TI  - Application of DNA typing methods and genetic analysis to epidemiology and
      taxonomy of Saccharomyces isolates.
AB  - We have previously described differences in phenotype and virulence among
      clinical and nonclinical isolates of Saccharomyces. To further characterize these
      isolates, a comparison of restriction fragment length polymorphism (RFLP)
      patterns and genetic analysis were done. The cellular DNA of each of 49 clinical
      and 11 nonclinical isolates of Saccharomyces was digested with the endonuclease
      EcoRI, and the resultant fragments were separated by electrophoresis. Sixty
      isolates were grouped on the basis of the presence (group B) or absence (group A)
      of a 3-kb band. Group A contained 43 isolates (35 clinical and 8 nonclinical
      isolates) in 31 discernible subgroups, and group B had 17 isolates (14 clinical
      and 3 nonclinical isolates) in 10 subgroups. Interestingly, six of eight known
      vaginal isolates were group B, with four of those six being identical. Virulence
      of isolates was associated with membership in group A (P = 0.03). Comparison of
      known members of sibling species within the genus Saccharomyces, which cannot be
      distinguished by standard biochemical tests, showed that S. paradoxus, S.
      bayanus, and S. cerevisiae could be differentiated by RFLP analysis. Genetic
      analysis of the isolates forming viable spores showed that most group A isolates
      were diploid and members of the species S. cerevisiae. Those group A and B
      isolates unable to form viable spores may be diploid hybrids between
      Saccharomyces species. The group B isolates that formed viable spores were
      tetraploid and may also be interspecific hybrids. Overall, clinical isolates of
      Saccharomyces were very heterogeneous and exhibited little clonality. RFLP
      pattern analysis could be a useful method of demonstrating transmission in
      patients with infection or between environmental sources and patients.

PMID- 9196203
TI  - Serological diagnosis of Chagas' disease: a potential confirmatory assay using
      preserved protein antigens of Trypanosoma cruzi.
AB  - The diagnosis of Chagas' disease relies mostly on data provided by immunologic
      tests, but inconclusive results often require elucidation, especially in blood
      banks. When six different types of Trypanosoma cruzi epimastigote antigens were
      studied by an immunoblotting assay (IBA), a preserved protein antigen (Ag PP) was
      found to present the most interesting immunochemical features because of its high
      reactivity with anti-T. cruzi antibodies. Thus, the IBA with Ag PP (PP IBA) was
      assessed with panels of coded and noncoded serum samples prepared in different
      laboratories, including the Brazilian Reference Laboratory for Chagas' Disease.
      It was found that serum samples from patients proved (clinically,
      eletrocardiographically, serologically, and epidemiologically) to have Chagas'
      disease consistently recognized 12 bands (140, 100, 85, 78, 59, 57, 46, 35, 27,
      23, 20, and 18 kDa) of Ag PP. In contrast, sera from nonchagasic patients,
      including patients with mucocutaneous leishmaniasis, were negative or reacted
      weakly, and one serum sample did not have more than five different bands. These
      bands were 78, 57, 46, 35, 27, 23, 20, or 18 kDa. A criterion was adopted to
      interpret the results obtained in the PP IBA. The criterion considered positive a
      serum sample recognizing all 12 bands and considered negative a serum sample that
      did not recognize any of the bands except the eight nonspecific bands mentioned
      above. The PP IBA indicated maximum sensitivity and specificity as well as high
      positive and negative predictive values. The data demonstrate that the PP IBA
      discriminates chagasic from nonchagasic infections and seems to be applicable as
      a confirmatory assay for elucidating inconclusive results obtained by standard
      serology.

PMID- 9196204
TI  - Evidence for numerous omp1 alleles of porcine Chlamydia trachomatis and novel
      chlamydial species obtained by PCR.
AB  - A nested PCR for genus-specific amplification of the Chlamydia omp1 locus was
      established. This PCR detected single template molecules in 200-microl specimen
      aliquots. Amplified chlamydial omp1 alleles were typed by heminested species PCRs
      and allele PCRs. We applied this method to 407 specimens from several host
      animals with various clinical conditions, and we detected prevalences of
      chlamydiae from 6 to 50%. Amplicons from peacock enteritis and equine infertility
      specimens were not typeable according to present omp1 allelic criteria for the
      chlamydial species. DNA sequencing revealed novel omp1 alleles which were 29.9
      and 47.6% divergent in the deduced peptide sequences from the most closely
      related chlamydiae. Phylogenetic reconstruction indicated segregation of these
      alleles from the current four chlamydial species (90 and 97% bootstrap support),
      thus strongly suggesting the existence of additional chlamydial species. Allele
      typing of amplicons from swine with intestinal, urogenital, and respiratory
      infections demonstrated several unique omp1 allelic variants of Chlamydia
      trachomatis. These novel alleles had deduced peptide sequences which were 11.6 to
      19% divergent from porcine C. trachomatis S45. Mutations were clustered in the C
      terminal region of variable segment IV of the omp1 locus encoding subspecies and
      serovar determinants of the chlamydial major outer membrane protein, thus
      implying that there are numerous serovars of porcine C. trachomatis. These
      results demonstrate the need for routine application of sensitive genus-specific
      detection of chlamydiae in animal specimens and suggest a more prominent role
      than anticipated for chlamydiae in animal diseases.

PMID- 9196205
TI  - Comparative evaluation of the E test, agar dilution, and broth microdilution for
      testing susceptibilities of Helicobacter pylori strains to 20 antimicrobial
      agents.
AB  - The Epsilometer test (E test; AB Biodisk, Solna, Sweden), a new quantitative
      technique for the determination of antimicrobial susceptibility, was compared to
      reference methods (agar dilution and broth microdilution) for the antimicrobial
      susceptibility testing of Helicobacter pylori. Seventy-one H. pylori strains
      isolated from patients with duodenal ulcers were tested against 20 antimicrobial
      agents. The E test and the agar dilution method were carried out on Mueller
      Hinton agar; the broth microdilution method was performed with Mueller-Hinton
      broth. The E-test results showed excellent correlation with the agar dilution
      results, with 91.3 and 98.8% agreement within 1 and 2 log2 dilution steps,
      respectively, in a total of 1,350 tests. The correlation between the E-test
      results and the broth microdilution results was slightly higher, with 91.6 and
      99.1% agreement within 1 and 2 log2 dilution steps, respectively, in a total of
      1,317 tests. There were six major errors and two very major errors by the
      metronidazole E test compared to the results obtained by reference methods.
      Excellent agreement between E-test, agar dilution, and broth microdilution
      results was found for resistance to erythromycin (8%), clarithromycin (6%), and
      tetracycline (6%). Our results confirm that the E test is comparable to
      standardized methods for susceptibility testing. Therefore, the E test is a
      reliable and alternative method for testing H. pylori susceptibility to a wide
      range of antimicrobial agents in clinical practice.

PMID- 9196206
TI  - Descriptive profile of tuberculin skin testing programs and laboratory-acquired
      tuberculosis infections in public health laboratories.
AB  - The increase in numbers of cases of tuberculosis in the United States has placed
      greater demands on mycobacteriology laboratory workers to produce rapid and
      accurate results. The greater number of specimens generated by the increased
      emphasis on detecting the disease has placed these workers at greater risk of
      laboratory-acquired infection. We surveyed 56 state and territorial public health
      laboratories to determine the status of existing tuberculin skin testing (TST)
      programs and to evaluate the frequency of probable laboratory-acquired
      tuberculosis for each responding mycobacteriology laboratory. Probable laboratory
      acquired infections were determined by each laboratory's evaluation of
      occupational positions, duties, and employee histories and review of medical
      records. Two-step TST for new employees was routinely practiced in only 33% of
      responding laboratories, and mycobacteriology laboratorians were found to be most
      frequently screened when they were compared to employees of other departments. Of
      49 (88%) responding laboratories, 13 reported that 21 employees were TST
      converters from 1990 to 1994. Seven of these 21 employees were documented to have
      laboratory-acquired infections based on evaluations by their respective
      laboratories. Based on Centers for Disease Control and Prevention guidelines,
      converters are categorized on the basis of both a change in the size of the zone
      of induration and the age of the person being tested. By the definitions in the
      guidelines, 14 mycobacteriologists were identified as recent converters, 7 of
      whom were > or = 35 years of age and 4 of whom were exposed in the laboratory
      within a 2-year period. Inadequate isolation procedures, the high volume of
      specimen handling, and faulty ventilation accounted for these laboratory
      associated infections. These results suggest that more frequent periodic
      evaluations based on documented TST conversions for workers in mycobacterial
      laboratories should be performed, since this population is at increased risk of
      becoming infected with Mycobacterium tuberculosis. Although general assessments
      are necessary to accurately and effectively evaluate the risk of tuberculosis
      transmission, they are especially important for those working in high-risk areas
      within a public health laboratory.

PMID- 9196207
TI  - Comparison of nested PCR with immunofluorescent-antibody assay for detection of
      Ehrlichia canis infection in dogs treated with doxycycline.
AB  - A partial 16S rRNA gene was amplified in Ehrlichia canis-infected cells by nested
      PCR. The assay was specific and did not amplify the closely related Ehrlichia
      chaffeensis, Ehrlichia muris, Neorickettsia helminthoeca, and SF agent 16S rRNA
      genes. The assay was as sensitive as Southern hybridization, detecting as little
      as 0.2 pg of E. canis DNA. By this method, all blood samples from four dogs
      experimentally infected with E. canis were positive as early as day 4
      postinoculation, which was before or at the time of seroconversion. One hundred
      five blood samples from dogs from Arizona and Texas (areas of E. canis
      endemicity) and 30 blood samples from dogs from Ohio (area of E. canis
      nonendemicity) were examined by nested PCR and immunofluorescent-antibody (IFA)
      test. Approximately 84% of dogs from Arizona and Texas had been treated with
      doxycycline before submission of blood specimens. Among Arizona and Texas
      specimens, 46 samples were PCR positive (44%) and 80 were IFA positive (76%).
      Forty-three of 80 IFA-positive samples (54%) were PCR positive, and 22 of 25 IFA
      negative samples (88%) were negative in the nested PCR. None of the Ohio
      specimens were IFA positive, but 5 specimens were PCR positive (17%). Our results
      indicate that the nested PCR is highly sensitive and specific for detection of E.
      canis and may be more useful in assessing the clearance of the organisms after
      antibiotic therapy than IFA, especially in areas in which E. canis is endemic.

PMID- 9196208
TI  - Comparison of direct-plating and enrichment methods for isolation of Vibrio
      cholerae from diarrhea patients.
AB  - A direct-plating method on thiosulfate citrate bile salts sucrose agar (DIR-TCBS)
      in conjunction with enrichment in alkaline peptone water (APW) incubated for both
      6 h and 24 h followed by subculture onto TCBS (APW6h-TCBS and APW24h-TCBS,
      respectively) was performed on 16,034 rectal swab samples for isolating Vibrio
      cholerae. A total of 2,932 (18.3%) rectal swab samples were positive for V.
      cholerae O1 biotype El Tor, with the Ogawa serotype constituting 99.2% of the
      isolates. There were no significant differences in V. cholerae O1 isolation rates
      between the three culture systems nor between the combinations of any two
      systems. However, direct plating plus enrichment demonstrated a significantly
      higher V. cholerae O1 isolation rate than DIR-TCBS alone (P < 0.02). Conversely,
      enrichment procedure, alone or in combination with DIR-TCBS, yielded
      significantly more (P < 0.0001) V. cholerae non-O1 isolates than DIR-TCBS alone.
      The length of incubation time of the enrichment broth, 6 h, offers no significant
      advantages over 24 h for the isolation of V. cholerae O1 and non-O1. A 24-h
      enrichment broth incubation period has the practical advantage of being easy to
      integrate into a normal laboratory workday, whereas 6-h broth enrichment,
      although more commonly recommended, requires that arrangements be made for after
      hours subculture.

PMID- 9196209
TI  - Simple, speedy, sensitive, and specific serodiagnosis of pertussis by using a
      particle agglutination test.
AB  - We developed a particle agglutination test (KPA) with poly(gamma-methyl L
      glutamate) as the solid particle for measurement of pertussis toxin (PT)
      antibody. In this study, KPA was assessed as a means of serodiagnosing pertussis,
      and the results were compared with those of indirect enzyme-linked immunosorbent
      assay (indirect ELISA) and the microagglutination test. First, four serum samples
      were collected from each of 21 healthy children: before and 4 weeks after
      receiving three primary doses of acellular pertussis vaccines and before and 4
      weeks after receiving a booster dose. In all 21 vaccinees, a significant rise in
      PT antibody titers was observed by KPA after each vaccination, and among all 84
      serum samples collected, an excellent correlation was demonstrated between the
      values obtained by indirect ELISA and those obtained by KPA (r = 0.92). Second,
      paired serum samples were collected at intervals of approximately 2 weeks from 51
      patients with culture-confirmed pertussis. A significant increase in titer
      (fourfold or more) was observed in 39 (76%) patients by KPA, 34 (67%) patients by
      indirect ELISA, and 23 (45%) patients by the microagglutination test. In acute-
      and convalescent-phase sera collected from 20 nonpertussis patients, there were
      no changes in titers by KPA. The KPA procedure was as simple as that of the
      microagglutination test, and the reaction time was only 2 h (or overnight). In
      this study, KPA was demonstrated to be a simple, speedy, sensitive, and specific
      serodiagnostic method for pertussis.

PMID- 9196210
TI  - Identification of Enterocytozoon bieneusi spores in respiratory samples from an
      AIDS patient with a 2-year history of intestinal microsporidiosis.
AB  - Enterocytozoon bieneusi, a microsporidian parasite, has been recognized since
      1985 as an agent of intestinal microsporidiosis leading to malabsorption
      syndrome, diarrhea, and weight loss in AIDS patients. Recently, however, we have
      identified E. bieneusi spores in the sputum, bronchoalveolar lavage, and stool
      samples of an AIDS patient with a 2-year history of intestinal microsporidiosis.
      The spores were characterized by Weber's chromotrope-based staining,
      immunofluorescence tests, and PCR. No microsporidia were detected in urine
      samples by the same techniques. PCR was performed with DNAs purified from
      specimens with E. bieneusi-, Encephalitozoon cuniculi-, Encephalitozoon hellem-,
      and Encephalitozoon (Septata) intestinalis-specific primers. Treatment with
      albendazole and loperamide resulted in an improvement of intestinal symptoms,
      without eradication of the parasite. To our knowledge, this is the second report
      of the identification of E. bieneusi spores in respiratory and enteric samples
      obtained from an AIDS patient. Although no pulmonary pathology could be
      established in either of these cases, it is now clear that E. bieneusi is capable
      of colonizing the respiratory tract and it is suggested that investigators should
      be aware of the possibility of finding E. bieneusi spores in respiratory
      secretions.

PMID- 9196211
TI  - Microscopic observation of progressive immobilization of leishmania promastigotes
      in acridine orange stain.
AB  - To rapidly isolate Leishmania donovani promastigotes in samples from Novy-MacNeal
      Nicolle (NNN) cultures, a method of staining with acridine orange was developed.
      Such vital staining combines the advantages of direct microscopic examination
      (e.g., observation of motility) with more accurate cytological and structural
      imaging of the stained parasites (usually obtained by Giemsa staining).
      Progressive immobilization of Leishmania promastigotes associated with a change
      in fluorescence color was also studied. Our findings may be useful for the early
      confirmation of a positive culture inoculated with a clinical sample.

PMID- 9196212
TI  - Determination of genotypes of hepatitis C virus in Venezuela by restriction
      fragment length polymorphism.
AB  - Hepatitis C virus genotypes in Venezuela were analyzed by restriction fragment
      length polymorphism in the 5' noncoding region. The absence of BstUI digestion
      was found to be a useful marker for genotype 2 specimens. From 122 serum samples,
      66, 20, and 2.5% were classified as genotypes 1, 2, and 3, respectively; 0.8%
      were classified as genotype 4; and 10% appeared to be mixed infections.

PMID- 9196213
TI  - Increased prevalence of genotype F hepatitis B virus isolates in Buenos Aires,
      Argentina.
AB  - The genomic coding region of the hepatitis B surface antigen (HBsAg) was
      partially sequenced from 12 HBsAg-positive sera of carriers residing in Buenos
      Aires, Argentina. A phylogenetic analysis groups the 12 isolates into genotypes A
      (n = 4), B (n = 1), D (n = 2), and F (n = 5). The occurrence of genotypes A and D
      is not unexpected, considering the mainly European origin of the studied
      population. The high prevalence of genotype F and its genetic composition support
      the suggestion that F strains originated in native populations of the New World.

PMID- 9196214
TI  - PCR-DNA probe assays for identification and detection of Prevotella intermedia
      sensu stricto and Prevotella nigrescens.
AB  - The purpose of this study was to construct PCR-DNA probe assays specific for
      Prevotella intermedia sensu stricto and Prevotella nigrescens based on the
      ability of randomly amplified polymorphic DNA (RAPD) fingerprinting to generate
      species-specific markers. The strategy included four steps: (i) construction of
      first-generation DNA probes from a 850-bp RAPD marker for P. intermedia sensu
      stricto and a 1,300-bp RAPD marker for P. nigrescens, (ii) cloning and sequencing
      of each RAPD marker, (iii) designing of primer pairs flanking specific internal
      sequences of 754 bp for P. intermedia sensu stricto and of ca. 1,100 bp for P.
      nigrescens, and (iv) synthesis (by PCR amplification) and digoxigenin labeling of
      quantities of DNA probes 754 and ca. 1,100 bp in size. The PCR-DNA probe assays
      combine either PCR amplification of a 754-bp specific sequence in the genomic DNA
      of strains of P. intermedia sensu stricto and hybridization with the 754-bp
      digoxigenin-labeled probe or amplification of a ca. 1,100-bp sequence of P.
      nigrescens and hybridization with the ca. 1,100-bp probe. Specific hybridization
      was observed with the amplified DNAs from 25 strains of P. intermedia and 24
      strains of P. nigrescens, and no reaction was observed with the PCR products from
      20 foreign species. The PCR-DNA probe assays described here should allow a highly
      specific and sensitive detection of P. intermedia sensu stricto and P. nigrescens
      in mixed infections.

PMID- 9196215
TI  - Improvement of growth of Chlamydia pneumoniae on HEp-2 cells by pretreatment with
      polyethylene glycol in combination with additional centrifugation and extension
      of culture time.
AB  - The following adaptations led to improved growth of Chlamydia pneumoniae on HEp-2
      cells compared to that by the standard method: monolayer preincubation with 7%
      polyethylene glycol (PEG), extension of incubation time to 7 days, and extension
      of incubation to 7 days in combination with centrifugation on days 3, 4, and 5.
      These adaptations resulted in approximate increases in numbers of inclusion
      forming units (IFU) of 2-, 5-, and 69-fold, respectively. A combination of
      preincubation with PEG, prolonged incubation, and centrifugation on days 3, 4,
      and 5 increased the numbers of IFU >300-fold. This is therefore recommended as
      the optimal method for culturing C. pneumoniae.

PMID- 9196216
TI  - Cross-reactions of reagents from streptococcal grouping kits with Streptococcus
      porcinus.
AB  - Streptococcus porcinus is usually associated with swine. Because we have received
      several isolates from human sources that had cross-reacted with commercial group
      B streptococcal reagents, we examined several commercial kits to determine the
      extent of this cross-reaction. Fifteen reference and 15 clinical strains of S.
      porcinus were tested for cross-reactions with group B streptococcal reagents from
      12 different commercial kits. Cross-reactions were detected with all group B
      reagents, but the number of cross-reactions varied with each kit. We recommend
      that manufacturers of reagents designed to identify group B streptococci by
      serologic methods test their reagents for cross-reactions with selected S.
      porcinus cultures or antigens.

PMID- 9196217
TI  - Monoclonal antibodies capable of distinguishing epizootic from enzootic varieties
      of subtype 1 Venezuelan equine encephalitis viruses in a rapid indirect
      immunofluorescence assay.
AB  - We used previously characterized murine monoclonal antibodies to develop a panel
      useful in subtyping Venezuelan equine encephalitis (VEE) viruses by an indirect
      fluorescent antibody assay. This panel worked well with either prototype VEE
      viruses or a series of more recent VEE virus isolates. The panel is particularly
      useful for rapidly differentiating VEE viruses with epidemic-epizootic potential
      from other endemic varieties of this virus. Using this panel, we identified an
      antigenic variant of prototype VEE subtype 1E virus currently present in Mexico.
      This antigenic change in the E2 glycoprotein was confirmed by enzyme-linked
      immunosorbent assay. Because VEE virus virulence has been associated in part with
      the E2 glycoprotein, this observed antigenic change in the 1E virus E2
      glycoprotein may explain the apparent equine virulence of this unusual VEE 1E
      virus.

PMID- 9196218
TI  - Study of transmission routes of Helicobacter pylori in relation to seroprevalence
      of hepatitis A virus.
AB  - The seroprevalence of Helicobacter pylori in a group of 1,043 healthy Japanese
      people was compared with that of hepatitis A virus (HAV), which was used as a
      marker of fecal-oral exposure. No statistically significant relationship was
      observed between seropositivity for HAV and that for H. pylori. Therefore, the
      fecal-oral spread of H. pylori is of limited relevance in Japan.

PMID- 9196219
TI  - Molecular detection and identification of Paracoccidioides brasiliensis.
AB  - Nearly 800 nucleotides from the 5' terminus of the 28S ribosomal gene of
      Paracoccidioides brasiliensis were sequenced, and a 14-base DNA probe specific
      for this species was identified. Hybridization results showed that the probe
      identified P. brasiliensis ribosomal DNA in a panel of ribosomal DNAs
      representing a total of 48 species of fungi.

PMID- 9196220
TI  - Comparison of methods for extraction of nucleic acid from hemolytic serum for PCR
      amplification of hepatitis B virus DNA sequences.
AB  - The sensitivity of PCR for the amplification of target nucleic acid sequences in
      clinical diagnostics may often be reduced due to the presence of inhibitory
      factors. Hemolytic serum contains a number of PCR inhibitors, one of which is
      hemin. In this study we have found that conventional methods of DNA extraction
      were not sufficient for the removal of PCR-inhibitory compounds in hemolytic
      serum. We have therefore compared the efficiency of several commercial and
      noncommercial methods of nucleic acid purification from hemolytic serum samples
      prior to PCR amplification. Separation with the QIAamp HCV kit, dialysis with
      Millipore filters, and bovine serum albumin absorption were all found to be
      suitable extraction methods for eliminating inhibitors from hemolytic serum for
      PCR amplification. Using these methods we were able to detect very low levels of
      hepatitis B virus DNA in hemolytic serum.

PMID- 9196221
TI  - Comparison of Madin-Darby canine kidney cells (MDCK) with a green monkey
      continuous cell line (Vero) and human lung embryonated cells (MRC-5) in the
      isolation of influenza A virus from nasopharyngeal aspirates by shell vial
      culture.
AB  - We report a comparative study of the MDCK, Vero, and MRC-5 cell lines in the
      isolation of the influenza A (IA) virus. We studied 746 samples in which 63 IA
      viruses were isolated. The MDCK line displayed 100% sensitivity, the Vero line
      displayed 71.4%, and the MRC-5 displayed 57.1%. The MDCK line showed a
      statistically significant difference with respect to the Vero line (P = 0.001)
      and the MRC-5 line (P = 0.001). The quantitative sensitivity analysis showed the
      MDCK line to be superior to the other lines. It seems that the MDCK line is still
      one of the most recommendable for the isolation of the IA virus from respiratory
      samples.

PMID- 9196222
TI  - Correlation of in vitro susceptibility results for amoxicillin-clavulanate and
      ampicillin-sulbactam tested against Escherichia coli.
AB  - The results of amoxicillin-clavulanate (AUG) and ampicillin-sulbactam (A/S)
      susceptibility testing by three different susceptibility testing methods, the
      MicroScan, Etest, and Kirby-Bauer methods, for 61 consecutive isolates of
      ampicillin-resistant Escherichia coli from different patients were compared.
      There was poor correlation of results for the two agents, the most and least
      marked discrepancies being observed by the MicroScan method (86.9% susceptible to
      AUG and 4.9% susceptible to A/S) and the Kirby-Bauer method (39.4% susceptible to
      AUG and 32.8% susceptible to A/S), respectively. More organisms were susceptible
      to AUG than A/S, regardless of the susceptibility testing methodology. The
      results from a College of American Pathologists survey with one E. coli isolate
      tested at different institutions also indicated greater susceptibility to AUG
      than to A/S. These agents are thought to be equally efficacious clinically. The
      discrepancies observed among methods for each antimicrobial inhibitor combination
      and the discrepancies observed between the two agents by each testing method
      suggest that the breakpoints for these agents need to be reevaluated.

PMID- 9196223
TI  - Emergence of rifampin-resistant Rhodococcus equi in an infected foal.
AB  - To investigate the emergence of rifampin resistance in Rhodococcus equi strains
      isolated from foals and their environment in Japan, we compared the in vitro
      antimicrobial susceptibilities to rifampin of 640 isolates from 64 infected foals
      and 98 soil isolates from their horse-breeding farms. As a control, 39 human
      isolates from patients with and without AIDS were also tested for susceptibility
      to rifampin. All of the isolates showed rifampin sensitivity, except isolates
      from one infected foal and two patients with AIDS that showed rifampin
      resistance. To investigate the emergence of rifampin-resistant R. equi in the
      infected foal, which had received rifampin monotherapy for a month before
      euthanasia, 99 isolates of R. equi from the lesions and 20 isolates from the
      intestinal contents of the one foal with rifampin-resistant organisms were
      analyzed for rifampin susceptibilities, pathogenicities, and ribotypes. Of the 99
      isolates from the lesions, all of which were virulent R. equi strains containing
      a virulence plasmid with a size of 85 or 90 kb, 90 (91%) isolates were rifampin
      resistant (MIC, > or = 12.5 microg/ml). On the other hand, of the 20 isolates
      from the intestinal contents, 11 (55%) isolates showed rifampin resistance (MIC,
      > or = 25 microg/ml), and 5 of them were avirulent R. equi strains. Among these
      101 rifampin-resistant R. equi isolates with and without virulence plasmids
      characterized by ribotyping, 58 were type I, 20 were type II, 11 were type III,
      and 12 were type IV. These results demonstrated that at least eight different
      rifampin-resistant R. equi strains emerged concurrently and respectively from the
      different lesions and intestinal contents of the infected foal.

PMID- 9196225
TI  - Susceptibilities to co-trimoxazole of pathogens isolated from blood and stool
      specimens in Abidjan, Ivory Coast, 1994 to 1996.

PMID- 9196224
TI  - Expression and self-assembly of recombinant capsid protein from the antigenically
      distinct Hawaii human calicivirus.
AB  - The Norwalk and Hawaii viruses are antigenically distinct members of the family
      Caliciviridae and are considered to be important etiologic agents of epidemic
      gastroenteritis, with most studies focusing on the role of Norwalk virus. To
      further investigate the importance of Hawaii virus, Hawaii virus-like particles
      (VLPs) were produced by expression of its capsid protein in the baculovirus
      system and these VLPs were used as the antigen in an enzyme-linked immunosorbent
      assay that was efficient in the detection of a serologic response to Hawaii
      virus. The ready availability of Hawaii VLPs should enable larger-scale
      epidemiological studies to further elucidate the importance of this agent.

PMID- 9196226
TI  - Kingella kingae bacteremia in an immunocompetent adult host.

PMID- 9196227
TI  - Instability of a Shiga toxin type 2 gene in Enterobacter cloacae.

PMID- 9196228
TI  - A novel device for the prevention of airborne infections.

PMID- 9196229
TI  - Femoral vascular catheterization in critically ill infants and children.
AB  - The success rate and complications from femoral arterial and venous
      catheterization in infants and children in a university affiliate pediatric
      intensive care unit were determined prospectively over a 2-year period. We also
      performed a meta-analysis from published literature to determine the combined
      estimates of noninfectious and infectious complications (with 95% confidence
      limits) using the inverse variance-weighted method. Success rates were 94.5% and
      94.4% for femoral arterial (n=110) and venous (n=89) catheterizations,
      respectively, and were related to operator expertise, age, and hemodynamic
      status. Median age was 2.4 years and 1.1 year for arterial and venous
      catheterizations, respectively. Immediate complications were hematoma (10.9%
      arterial, 16.8% venous) and minor bleeding (13.6% arterial, 13.5% venous).
      Decreased pulses occurred with 7.7% of arterial catheterizations, and lower limb
      swelling occurred in 9.5% of venous catheterizations. Vascular complications
      occurred only in infants and resolved within 7-14 days. Catheter-related
      infections occurred in 1.9% of arterial and 3.6% of venous catheterizations. The
      mean duration of catheterization was 5.3 days and 6.3 days with femoral arterial
      and venous catheterizations, respectively. Meta-analysis of published studies
      shows that the estimates for noninfectious complications were 5.0%, 10.1%, 1.1%,
      and 1.8% for femoral arterial, femoral venous, axillary arterial, and nonfemoral
      venous catheters, respectively. The estimates for catheter-related infection were
      2.5%, 3.7%, and 3.0% for femoral arterial, femoral venous, and nonfemoral venous
      catheters, respectively. The meta-analytic estimates for complication rates from
      published literature are not significantly different from the rates observed in
      our study. Femoral arterial and venous catheterization in infants and children
      are safe with an expected high success rate and acceptably low complication
      rates.

PMID- 9196230
TI  - Sleep apnea in patients receiving growth hormone.
AB  - Among 145 patients treated with recombinant human growth hormone (GH), four
      developed sleep apnea (two obstructive, two mixed) associated with tonsillar and
      adenoidal hypertrophy in three. These four patients had no local risk factors
      predisposing to upper airway obstruction (i.e., frequent pharyngitis or
      sinusitis). Clinical and/or polysomnographic features of sleep apnea improved
      following cessation of GH therapy in one patient, and following tonsillectomy and
      adenoidectomy in all patients. The present observations indicate that, albeit
      rarely, obstructive and/or central sleep apnea may occur in children treated with
      GH. Polysomnography should be considered if symptoms of snoring, interrupted
      sleep, daytime somnolence-particularly if associated with tonsillar hypertrophy
      appear in children during GH therapy.

PMID- 9196231
TI  - Life expectancy and social adaptation in individuals with Down syndrome with and
      without surgery for congenital heart disease.
AB  - Life expectancy and social adaptation in 373 children with Down syndrome with and
      without congenital heart disease (CHD) were assessed retrospectively. Survival at
      age 24 years was 92.2% for patients without CHD (n=200), and 74.6% for those with
      CHD (n=173). Survival for those who underwent operation for cardiovascular
      lesions (n=95) was 87.8%, and for those not operated on despite hemodynamically
      significant cardiovascular lesions (n=39), it was 41.4%. Cardiac functional
      capacity was better in the children without congenital heart disease and in the
      group operated on, where most patients also attained good social adaptation. We
      conclude that children with Down syndrome with congenital heart disease should
      undergo early cardiac evaluation and surgery if indicated.

PMID- 9196232
TI  - Nontraumatic dental emergencies in a pediatric emergency department.
AB  - The objectives of this study were to describe nontraumatic dental emergencies
      among children treated in a pediatric emergency department. The children studied
      received emergency treatment for a nontraumatic dental problem from December 1992
      through November 1993. Among the 1,459 children treated for dental emergencies,
      949 had a nontraumatic emergency (65%) and were enrolled in this study. Patients
      ranged in age from 1 month to 19 years, with a mean age of 6.9 years. Fifty-two
      percent of patients were male. The teeth were involved in 99% of cases. An
      abscess was present in 33% of patients; and among these patients, 26% also had a
      fistula. Pericoronitis was seen in 4% of patients, primary viral stomatitis in
      1%, and an eruption hematoma in 0.5%. Caries is the etiology of the problem
      prompting the emergency department visit in 73% of patients, and baby bottle
      caries accounted for 18% of all cases of caries. Other etiologies included the
      late effects of trauma (8%), iatrogenic (7%), idiopathic (3%), and periodontal
      processes (2%). Tooth extraction was performed in 45% of patients. Findings of
      this large consecutive series provide a better understanding of this type of
      visit to the pediatric emergency department.

PMID- 9196233
TI  - Evaluation of the erythrocyte sedimentation rate in children presenting with
      limp, fever, or abdominal pain.
AB  - An erythrocyte sedimentation rate (ESR) is commonly ordered as part of the
      evaluation of patients with nonspecific but potentially serious symptoms. To
      investigate the performance of ESR in this setting, we used a computerized
      database and medical chart review to identify children (n=299) with ESR done for
      a previously undiagnosed condition. Medical records were reviewed to determine
      symptoms at presentation, referral status, and subsequent diagnoses, which were
      classified as serious (n=93) or benign (n=206). We found that serious underlying
      disease was about 7 times as likely in patients with ESR>50 mm/hr (57/102) than
      in patients with ESR<20 mm/hr (7/89). Although the prevalence of serious disease
      was higher among referral patients, the likelihood ratios were similar for
      referral and primary-care patients. An erythrocyte sedimentation rate greater
      than 50 mm/hr was most informative in patients presenting with limp (likelihood
      ratio [LR] =8.2) and abdominal pain (LR=6.0) and least informative in patients
      presenting with fever (LR=2.5). On the other hand, an ESR<20 mm/hr is reassuring
      in patients presenting with fever (LR=0) or limp (LR=0.3), but not in patients
      presenting with abdominal pain (LR=0.8). An ESR between 20 and 50 mm/hr (23% of
      the patients) provided little information (LR 1.2-1.5) in each of the three
      groups. These results suggest that the ESR often provides useful information
      about the likelihood of serious illness among children presenting with worrisome
      but nonspecific symptoms, in particular in patients presenting with limp.

PMID- 9196234
TI  - Does early supplementation affect long-term breastfeeding?
AB  - The purpose of this secondary data analysis from two different samples was to
      examine the effect of early supplementation with manufactured milks on
      breastfeeding status at 20 weeks postpartum in mothers of healthy term infants.
      In two convenience samples of 120 and 223, respectively, breastfeeding mothers
      were followed up for 20 weeks postpartum or until weaning occurred. The
      breastfeeding rate at 20 weeks postpartum was significantly greater for mothers
      who reported feeding exclusively mother's milk the second week after delivery
      compared with mothers who breastfed and simultaneously supplemented with
      manufactured infant milks. Of the mothers in samples one and two who exclusively
      fed human milk during week 2 postpartum, 63.0% and 59.7%, respectively, were
      still breastfeeding at week 20, compared with 28.1% and 24.2%, respectively, who
      supplemented with artificial milks. There was no significant difference between
      these two groups of mothers and their intended duration of breastfeeding. Early
      introduction of supplemental bottles of artificial milks is associated with a
      decrease in the amount of human milk the infant receives as well as with early
      weaning.

PMID- 9196235
TI  - Meningococcal meningitis revisited: normocellular CSF.

PMID- 9196236
TI  - Severe coughing and gagging episode in an adolescent with a chronic
      laryngotracheal foreign body: a case report.

PMID- 9196237
TI  - Transient myeloid dysplasia due to valproic acid.

PMID- 9196238
TI  - Natural history of vesicoureteral reflux in siblings.

PMID- 9196240
TI  - Early (99m)Tc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first
      time urinary tract infection.

PMID- 9196241
TI  - Fiberoptic phototherapy device unlikely to be cause of "thermal" skin injury.

PMID- 9196242
TI  - Nasogastric/orogastric suction for postoperative vomiting. Is it a benign
      procedure in pediatric anesthesia?

PMID- 9196244
TI  - The smoking gun and the damage done: genetic alterations in the lungs of smokers.

PMID- 9196243
TI  - Water chlorination, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX),
      and potential cancer risk.

PMID- 9196245
TI  - Helicobacter pylori and the cell cycle.

PMID- 9196246
TI  - Chemotherapy benefits nearly all early breast cancer patients.

PMID- 9196247
TI  - "Rescue" agent may circumvent rare but deadly complication from chemotherapy.

PMID- 9196248
TI  - Research on bone metastases quickens its pace.

PMID- 9196249
TI  - Researchers expand genetic epidemiology of BRCA genes.

PMID- 9196250
TI  - Carcinogenicity of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5
      hydroxy-2(5H)-furanone in the rat.
AB  - BACKGROUND: Several epidemiologic studies have suggested that the consumption of
      chlorinated drinking water may be associated with the development of certain
      cancers in humans. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a
      byproduct of the chemical reactions that occur in chlorinated drinking water, has
      been found to be mutagenic in bacteria and mammalian cells; however, its
      potential to cause tumors in animals has not been tested previously. PURPOSE: The
      objective of this study was to evaluate the carcinogenicity of MX in rats given
      MX in their drinking water. METHODS: MX was administered to male and female
      Wistar rats (50 rats per dose group) in drinking water for 104 weeks at
      concentrations yielding the average daily doses of MX of 0.4 mg/kg of animal
      weight (low dose), 1.3 mg/kg (mid dose), and 5.0 mg/kg (high dose) for males and
      0.6 mg/kg, 1.9 mg/kg, and 6.6 mg/kg for females, respectively. Control rats
      received water from the same source used for preparation of the MX dose
      formulations (after its adjustment to the same pH range). Body weight, clinical
      signs, and food and water consumption were recorded regularly. At the end of the
      treatment period, the animals were killed and full histopathologic analysis was
      performed on 47 tissues and all lesions. RESULTS: Dose-dependent increases in
      tumor incidence were observed in rats given MX-containing drinking water; the
      same MX doses had no obvious toxic effects on animals. MX consumption increased
      most drastically the prevalence of follicular adenoma (up to 43% and 72% in high
      dose males and females, a test [one-sided] for positive trend in all dose groups
      P = .0045 and P = .0000, respectively) and carcinoma (55% [P = .0000] and 44% [P
      = .0000], respectively) in thyroid glands and cholangioma in the liver (8% [P =
      .0009] and 66% [P = .0000] in the high-dose males and females, respectively).
      Among rats given the higher doses of MX in their drinking water, cortical
      adenomas of the adrenal glands were increased in both sexes, alveolar and
      bronchiolar adenomas of the lungs and Langerhans' cell adenomas of the pancreas
      were increased in males, and lymphomas, leukemias, and adenocarcinomas and
      fibroadenomas of the mammary glands were increased in females. Even the lowest MX
      dose studied was carcinogenic. CONCLUSION: MX is a potent carcinogen in both male
      and female rats, and it causes tumors at doses that are not overtly toxic to
      rats. IMPLICATIONS: Although these findings cannot be extrapolated to humans, MX
      should be studied as a candidate risk factor in the possible association between
      consumption of chlorinated drinking water and cancer in humans.

PMID- 9196251
TI  - Clonal genetic alterations in the lungs of current and former smokers.
AB  - BACKGROUND AND PURPOSE: Genetic damage has been identified at multiple
      chromosomal sites (i.e., loci) in lung cancer cells. We questioned whether
      similar damage could be detected in the bronchial epithelial cells of chronic
      smokers who do not have this disease. METHODS: Biopsy specimens from six
      different bronchial regions were obtained from 54 chronic smokers (40 current
      smokers and 14 former smokers). The presence of squamous metaplasia and dysplasia
      (abnormal histologic changes) in the specimens was documented by examination of
      hematoxylin-eosin-stained sections, and a metaplasia index ([number of biopsy
      specimens with metaplasia/total number of biopsy specimens] x 100%) was
      calculated for each subject. Loss of heterozygosity (i.e., loss of DNA sequences
      from one member of a chromosome pair) involving microsatellite DNA at three
      specific loci-chromosome 3p14, chromosome 9p21, and chromosome 17p13-was
      evaluated by means of the polymerase chain reaction. Fisher's exact test and
      logistic regression analysis were used to assess the data. Reported P values are
      two-sided. RESULTS: Data on microsatellite DNA status at chromosomes 3p14, 9p21,
      and 17p13 were available for 54, 50, and 44 subjects, respectively. The numbers
      of individuals who were actually informative (i.e., able to be evaluated for a
      loss of heterozygosity) at the three loci were 36 (67%), 37 (74%), and 34 (77%),
      respectively. DNA losses were detected in 27 (75%), 21 (57%), and six (18%) of
      the informative subjects at chromosomes 3p14, 9p21, and 17p13, respectively.
      Fifty-one subjects were informative for at least one of the three loci, and 39
      (76%) exhibited a loss of heterozygosity. Forty-two subjects were informative for
      at least two of the loci, and 13 (31%) exhibited losses at a minimum of two loci.
      Loss of heterozygosity at chromosome 3p14 was more frequent in current smokers
      (22 [88%] of 25 informative) than in former smokers (five [45%] of 11
      informative) (P = .01) and in subjects with a metaplasia index greater than or
      equal to 15% (21 [91%] of 23 informative) than in subjects with a metaplasia
      index of less than 15% (six [46%] of 13 informative) (P = .003). In five
      informative individuals among nine tested nonsmokers, a loss of heterozygosity
      was detected in only one subject at chromosome 3p14 (P = .03), and no losses were
      detected at chromosome 9p21 (P = .05). CONCLUSIONS: Genetic alterations at
      chromosomal sites containing putative tumor-suppressor genes (i.e., 3p14 and the
      FHIT gene, 9p21 and the p16 gene [also known as CDKN2], and 17p13 and the p53
      gene [also known as TP53]) occur frequently in the histologically normal or
      minimally altered bronchial epithelium of chronic smokers.

PMID- 9196252
TI  - Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell
      proliferation from apoptosis.
AB  - BACKGROUND: Infection with Helicobacter pylori induces chronic gastritis in
      virtually all infected persons, and such gastritis has been associated with an
      increased risk of developing gastric cancer. This risk is further enhanced with
      cagA+ (positive for cytotoxin-associated gene A) H. pylori strains and may be a
      consequence of induced gastric cell proliferation and/or alteration in apoptosis
      (programmed cell death) in the gastric epithelium. PURPOSE: To determine whether
      the H. pylori cagA genotype and another virulence-related characteristic, the
      vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial
      cell proliferation, apoptosis, and the histologic parameters of inflammation and
      injury, we quantitated these characteristics in infected and uninfected persons.
      METHODS: Fifty patients underwent upper gastrointestinal endoscopy, and biopsy
      specimens were taken. Apoptotic cells in the specimens were quantitated after
      terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin
      deoxyuridine triphosphate; epithelial cell proliferation was scored by
      immunohistochemical analysis of the proliferation-associated antigen Ki-67.
      Antibodies directed against H. pylori and CagA protein were measured in the serum
      of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori
      genomic DNA, by use of the polymerase chain reaction, was performed to determine
      the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell
      degeneration, mucin depletion, intestinal metaplasia, glandular atrophy, and
      vacuolation were each scored in a blinded manner. Reported P values are two
      sided. RESULTS: Persons harboring cagA+ strains (n = 20) had significantly higher
      gastric epithelial proliferation scores than persons infected with cagA-strains
      (n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but
      the difference in cell proliferation between the latter two groups was not
      statistically significant. The number of apoptotic cells per 100 epithelial cells
      (apoptotic index) in persons infected with cagA+ strains was lower than in
      persons infected with cagA-strains (P = .05). Apoptotic indices in the cagA+
      group were similar to those in the uninfected group (P = .2). Epithelial cell
      proliferation was significantly correlated with acute gastric inflammation, but
      only in the cagA+ group (r = .44; P = .006). The cagA+ and vacA s1a genotypes
      were found to be concordant, confirming the close relationship between these
      virulence-related genotypes. CONCLUSIONS: Gastric mucosal proliferation was
      significantly correlated with the severity of acute gastritis in persons infected
      with cagA+ vacA s1a strains of H. pylori. This increased proliferation was not
      accompanied by a parallel increase in apoptosis. IMPLICATIONS: Increased cell
      proliferation in the absence of a corresponding increase in apoptosis may explain
      the heightened risk for gastric carcinoma that is associated with infection by
      cagA+ vacA s1a strains of H. pylori.

PMID- 9196253
TI  - Identification of tobacco-specific carcinogen in the cervical mucus of smokers
      and nonsmokers.
AB  - BACKGROUND: In 1996, an estimated 15,700 new cases of cancer of the uterine
      cervix and 4,900 deaths from this disease were expected to occur in the United
      States. In a recent international study, human papillomavirus DNA was found in
      more than 90% of cervical tumor specimens examined, irrespective of the
      nationality of the patients from whom the samples were obtained. Although
      infection with human papillomavirus is the major known risk factor for the
      development of cervical cancer, it alone is not sufficient. Other etiologic
      factors that have been associated with this disease include deficiencies in
      micronutrients, lower socioeconomic status, oral contraceptive use, and cigarette
      smoking. Several compounds from cigarette smoke (nicotine and its major
      metabolite, cotinine) have been identified in cervical mucus, and the occurrence
      of smoking-related DNA damage in the cervical epithelium has been documented.
      PURPOSE: This investigation was conducted to determine for the first time whether
      carcinogenic tobacco-specific N-nitrosamines are present in the cervical mucus of
      cigarette smokers and of nonsmokers (most likely as a result of environmental
      exposure). METHODS: Cervical mucus specimens from 15 smokers and 10 nonsmokers
      were subjected to supercritical fluid extraction with the use of carbon dioxide
      that contained 10% methanol, and the resultant extracts were analyzed for tobacco
      specific nitrosamines by use of a very sensitive method that involved gas
      chromatography and mass spectroscopy analyses. RESULTS: In a total of 16 samples
      obtained from 15 women who were current smokers (two samples from the same
      woman), we detected the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) at concentrations that ranged from 11.9 to 115.0 ng/g
      of mucus. Only one of a total of 10 cervical mucus specimens obtained from 10
      women who claimed to be nonsmokers did not contain detectable NNK, and NNK
      concentrations ranged from 4.1 to 30.8 ng/g of mucus in the specimens from the
      remaining nine women. The concentrations of NNK in specimens from cigarette
      smokers were significantly higher than those from nonsmokers (mean +/- standard
      deviation: 46.9 +/- 32.5 ng/g of mucus versus 13.0 +/- 9.3 ng/g of mucus; two
      tailed Student's t test, P = .004). CONCLUSION: The cervical mucus of cigarette
      smokers contains measurable amounts of the potent carcinogen NNK. This compound
      represents the first tobacco-specific carcinogen identified in this physiologic
      fluid of women who smoke cigarettes. The presence of NNK in the cervical mucus of
      nonsmokers is likely due to environmental exposure or to the fact that some of
      the subjects in this study may not have revealed that they occasionally smoked
      cigarettes. IMPLICATIONS: The presence of NNK in human cervical mucus further
      strengthens the association between cervical cancer and tobacco smoking.

PMID- 9196254
TI  - Recovery from 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced
      immunosuppression in A/J mice by treatment with nonsteroidal anti-inflammatory
      drugs.
AB  - BACKGROUND: We have previously reported that nonsteroidal anti-inflammatory drugs
      inhibit lung tumorigenesis induced by the tobacco-specific carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mice. PURPOSE: The aims of
      this study were to determine if NNK suppresses humoral (i.e., antibody) and
      cellular immune responses in mice and if nonsteroidal anti-inflammatory drugs
      could attenuate these immune responses. METHODS: Female A/J mice (7-8 weeks old)
      were fed nonsteroidal anti-inflammatory drugs starting 2 weeks before the
      beginning of NNK treatment (9.1 mg per mouse in total) and continuing through the
      7 weeks of NNK treatment. Eight groups (two control groups and six experimental
      groups) of 10 mice each were used per experiment. Animals in the two control
      groups received the same diet and water as animals in the six experimental
      groups; one control group received no nonsteroidal anti-inflammatory drugs or NNK
      and the other control group received only NNK. The primary humoral and cellular
      immune responses to the various treatments were assayed by the plaque-forming
      cell technique and by measurement of natural killer cell cytotoxic activity,
      respectively. At the end of each experiment, the animals were killed, blood was
      collected, plasma was prepared, and levels of the immune system modulator
      prostaglandin E2 were measured. RESULTS: NNK treatment inhibited the plaque
      forming cell response by approximately 50%; this inhibition was attenuated by
      treatment with sulindac or acetylsalicylic acid (P = .0001 for both). In
      contrast, treatment with naproxen, which had no chemopreventive (i.e., tumor
      inhibitory) efficacy, further increased by 26% (P = .05) the immunosuppressive
      effect of NNK. The cytotoxic activity of splenic natural killer cells against YAC
      1 cells was reduced by 60% (P = .002); treatment with acetylsalicylic acid (254
      mg/kg of diet) reduced the NNK-induced natural killer cell cytotoxicity
      inhibition by 50% (P = .02), whereas the administration of the specific
      cyclooxygenase-2 inhibitor NS-398 (7 mg/kg of diet) resulted in an almost
      complete recovery (approximately 95%, P = .04) of natural killer cell activity.
      The prostaglandin E2 plasma concentration was approximately 100% greater in NNK
      treated mice than in untreated mice. Treatment of the mice with nonsteroidal anti
      inflammatory drugs attenuated this elevation (from approximately 25% to 100%),
      and NS-398 (7 mg/kg of diet) was the most effective (100%). CONCLUSIONS AND
      IMPLICATIONS: The ability of various nonsteroidal anti-inflammatory drugs to
      inhibit NNK-induced carcinogenesis appears to be directly related to the ability
      of these drugs to inhibit NNK-induced immunosuppression. Our results suggest that
      the chemopreventive effect of nonsteroidal anti-inflammatory drugs may be
      mediated through the modulation of prostaglandin E2 synthesis.

PMID- 9196255
TI  - Angiogenesis as a prognostic indicator of survival in non-small-cell lung
      carcinoma: a prospective study.
AB  - BACKGROUND: Tumors acquire nutrients that are essential for continued growth and
      an avenue for dissemination to the rest of the body by inducing angiogenesis
      (i.e., the formation of new blood vessels). Preliminary studies involving a
      number of different kinds of cancer have indicated that an assessment of tumor
      angiogenesis may be useful in predicting disease outcome. PURPOSE: In a
      prospective study, we evaluated the relationship between tumor angiogenesis and
      survival for 407 patients with non-small-cell lung carcinoma who were treated
      with potentially curative surgery. METHODS: The study population consisted of 360
      male and 47 female patients who underwent surgery consecutively at the Department
      of Surgery, University of Pisa, Italy, from March 1991 through December 1994.
      Follow-up lasted through February 1996, with a median follow-up for living
      patients of 29 months (range, 15-60 months). An anti-CD34 monoclonal antibody,
      which is specific for endothelial cells, and standard immunohistochemical
      techniques were used to measure angiogenesis in tumor samples. Angiogenesis was
      quantified in terms of microvessel counts; the counts for single, high-power
      microscopic fields (magnification x250) in the three most intense areas of blood
      vessel growth for each sample were averaged. The median microvessel count in this
      series was 20, and the counts were categorized as follows: 1) low versus high (<
      or =20 versus >20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31
      40, and > or =41 microvessels). Disease-free and overall survival during follow
      up were assessed. Kaplan-Meier survival curves were modeled in a univariate
      analysis of patient and tumor characteristics; the Cox proportional hazards model
      was used in multivariate analysis. Reported P values are two-sided. RESULTS AND
      CONCLUSIONS: In the univariate analysis, patients with larger tumors (P for trend
      <.00001), a more advanced tumor stage (P for trend <.00001), a greater degree of
      regional lymph node involvement (P for trend <.00001), or more vascularized
      tumors (high versus low microvessel count, P<.00001) experienced significantly
      reduced overall survival. When microvessel counts were analyzed in five
      categories, a highly significant trend (P<.00001) toward worse prognosis was
      observed with increasing tumor vascularity. In multivariate analysis, tumor
      microvessel count (P<.00001), tumor size (P = .0006), and regional lymph node
      status (P<.00001) retained independent prognostic value with respect to overall
      survival; among these variables, tumor microvessel count, considered as a
      continuous variable, was the most important, with a relative hazard of death of
      8.38 (95% confidence interval = 4.19-16.78) associated with the highest
      microvessel counts. IMPLICATIONS: An evaluation of tumor angiogenesis may be
      useful in the postsurgical staging of patients with non-small-cell lung carcinoma
      and in identifying subsets of patients who may benefit from different
      postsurgical treatments.

PMID- 9196256
TI  - Could the rising levels of estrogen receptor in breast cancer be due to
      estrogenic pollutants?

PMID- 9196257
TI  - Concerns about recommending routine screening mammograms for women aged 40-49
      years.

PMID- 9196258
TI  - Baseline apoptosis of tumor cells as a response predictor to chemotherapy.

PMID- 9196259
TI  - Fertility and incidence of KRAS2 mutations in borderline ovarian adenocarcinomas.

PMID- 9196260
TI  - Class I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxylic acid blocks
      contextual but not cue conditioning in rats.
AB  - It is widely believed that metabotropic glutamate (mGlu) receptors play a
      potential role in memory formation. However, the particular function of different
      classes of mGluRs, or even subtypes, remains elusive. We show here that
      intraperitoneal injection of the class I selective antagonist 1-aminoindan-1,5
      dicarboxylic acid (AIDA) in concentrations of 0.18 or 1.8 mg/kg 25 min prior to
      acquisition training blocks hippocampus-dependent contextual, but not hippocampus
      independent cue, conditioning in rats. These data provide the first evidence for
      a specific role of mGlu receptors, class I in particular, in hippocampus
      dependent learning tasks.

PMID- 9196261
TI  - NMDA receptor antagonists prevent conditioned activation of intracranial self
      stimulation in rats.
AB  - Rats with bipolar electrodes implanted unilaterally into the ventral tegmental
      area were trained to lever-press for response contingent electrical stimulation
      (continuous reinforcement). After preliminary lever-press training, two types of
      daily sessions were held on 10 consecutive days: type T+, during which current
      intensity was set at the Threshold level and each response was accompanied by the
      visual signal (stimulus lights above the lever briefly went off); and type ST-,
      during which current was set at the SubThreshold level and there were no visual
      stimuli. On day 11, combination of the subthreshold current intensities and
      stimulus lights previously associated with the threshold stimulation (session
      type ST+) resulted in significantly elevated response rates compared to the
      performance under the subthreshold current without visual stimuli (session type
      ST-). This effect was dose dependently blocked by competitive NMDA receptor
      antagonist (+/-)-CPP ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid)
      and CGS 19755 (cis-4-(phosphonomethyl) piperidine-2-carboxylic acid). The present
      findings suggest that the activation of intracranial self-stimulation induced by
      a conditioned visual stimulus is dependent on the NMDA receptor functioning.

PMID- 9196262
TI  - Discrete versus cumulative dosing in dose-response discrimination studies.
AB  - This study describes the results of a 'side-by-side' comparison of two
      measurement techniques and two dosing regimens in a discrimination study using
      rats trained to either 10 mg/kg cocaine or 2 mg/kg 3,4
      methylenedioxymethamphetamine (MDMA). The measurements employed were either
      quantal or quantitative; the former an all-or-none correct lever selection
      measure and the latter a measure of all responses made at the time that the
      criterion for selection was met. The dosing regimens were either a discrete
      single injection of lower doses than used in training or a cumulative dose
      administration sequence, in an ascending order, during one session on two
      separate occasions. Results indicate that the cumulative dose-response
      relationships, as indicated by both the slope of the curve or the generated ED50
      value, for the discrete and cumulative dose response curves do not significantly
      differ. In addition, both the quantal and quantitative measurements yield almost
      identical ED50 values, thus allowing for accurate comparability of drug
      discrimination data using different techniques. The present experimentation
      employed two drugs known to produce heightened response rates which would not
      allow for behavioral suppression at the highest doses used either in discrete or
      cumulative regimens. The pharmacokinetics of the two drugs employed in the
      discrimination tests are considered and discussed in light of the advantages and
      disadvantages of each of the two methods employed.

PMID- 9196263
TI  - Intravenous self-administration of heroin, cocaine, and the combination in Balb/c
      mice.
AB  - Polydrug abuse, including the abuse of cocaine + heroin combinations (or
      'speedballs') is an increasingly significant problem. The use of genetically
      defined populations of mice has the potential to add considerably to the study of
      polydrug abuse. Balb/cByJ (Balb/c) mice have been shown to self-administer
      opiates, but not cocaine, therefore these mice were chosen for the initial
      characterization of intravenous self-administration of cocaine + heroin
      combinations. Mice were implanted with chronic indwelling jugular catheters and
      given the opportunity to self-administer heroin, cocaine or heroin + cocaine
      combinations. Heroin was self-administered, while, under the same conditions,
      none of the mice tested acquired cocaine self-administration. However, heroin +
      cocaine combinations were self-administered in naive mice as well as in mice that
      had failed to self-administer cocaine alone. The heroin + cocaine combination
      dose-effect curve resembled the heroin dose-effect curve. It is hypothesized that
      heroin may interact with effects of cocaine that function to limit self
      administration in Balb/c mice, facilitating the acquisition and maintenance of
      self-administration of cocaine + heroin combinations.

PMID- 9196264
TI  - L-701,324, a glycine/NMDA receptor antagonist, blocks the increase of cortical
      dopamine metabolism by stress and DMCM.
AB  - Dopamine metabolism, as reflected by the concentration of dihydroxyphenylacetic
      acid (DOPAC), in the medial prefrontal cortex was significantly increased
      following 30 min immobilisation stress or systemic administration of the
      benzodiazepine/GABA(A) receptor inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta
      carboline-3-carboxylate (DMCM). The response to stress was attenuated by
      pretreatment of rats with the benzodiazepine/GABA(A) receptor agonists diazepam
      and zolpidem. Furthermore, pretreatment with R-(+)-3-amino-1-hydroxypyrrolid-2
      one (R-(+)-HA-966), a low efficacy partial agonist, and 7-chloro-4-hydroxy-3(3
      phenoxy) phenylquinolin-2-(H)-one (L-701,324) a novel, high affinity, full
      antagonist at the glycine/NMDA receptor attenuated the response to both stress
      and DMCM. These results demonstrate that antagonists at the glycine/NMDA receptor
      complex are comparable with benzodiazepine/GABA(A) receptor agonists in their
      ability to prevent activation of the mesocortical dopamine system by stress and
      GABA(A) receptor inverse agonists. Results are discussed in relation to the
      interaction between glycine/NMDA receptor antagonists, the mesocorticolimbic
      dopamine system and stress related disorders.

PMID- 9196265
TI  - Regulation of [3H]norepinephrine release from guinea pig hippocampus by sigma2
      receptors.
AB  - The binding profile of the sigma2 receptor ligand endo-N-(8-methyl-8
      azabicyclo[3.2.1.]oct-3-yl)-2,3-dihydro-(1-methyl)eth yl-2-oxo-1H-benzimidazole-1
      carboxamidehydrochloride (BIMU-8) had previously been determined, but its
      agonist/antagonist status at sigma2 receptors had not been identified. We
      therefore investigated the effects of BIMU-8 for its ability to regulate the
      stimulated release of [3H]norepinephrine from slices of guinea pig hippocampus.
      BIMU-8 alone, at a concentration chosen to occupy 50% of sigma2 receptors, had no
      significant effect on N-methyl-D-aspartate (NMDA)-stimulated release of
      [3H]norepinephrine. We have shown previously that the sigma receptor agonist (+)
      pentazocine inhibits NMDA-stimulated release in a concentration-dependent manner,
      producing a biphasic inhibition curve. Similarly, the sigma receptor agonist
      1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl
      )cyclohexylamine (BD737) produced a broad inhibition curve. The inhibition by low
      concentrations of (+)-pentazocine or BD737 that selectively activated sigma1
      receptors was reversed by the sigma1-selective receptor antagonist (1
      (cyclopropylmethyl)-4-2'-oxoethyl)piperidine HBr (DuP 734). In the current study,
      when the sigma1 component of inhibition by (+)-pentazocine was blocked by DuP
      734, the remaining component of inhibition mediated by sigma2 receptors was
      reversed by BIMU-8. Our results suggest that (1) BIMU-8 is an antagonist at
      sigma2 receptors and that (2) sigma2 receptors contribute to regulation of
      norepinephrine release in guinea pig hippocampus.

PMID- 9196267
TI  - Concerning the effect of the K+ channel blocking agent glibenclamide on ischaemic
      and reperfusion arrhythmias.
AB  - Reports on effects of ATP-dependent K+ channel modulating drugs on ischaemia
      induced cardiac arrhythmias have been scarce and contradictory. The channel
      blocking agent glibenclamide (glyburide) has been considered as an antiarrhythmic
      candidate, because it antagonizes the ischaemic K+ efflux and the shortening of
      the refractory period. In the present investigation its effects were tested,
      therefore, in rat hearts with coronary occlusion and reperfusion. In untreated
      hearts, tachyarrhythmias occurred during the reperfusion, and less pronounced
      during the coronary occlusion itself. Large amounts of adenosine and its
      degradation products were released during the coronary reperfusion, particularly
      from hearts which developed ventricular fibrillation. Glibenclamide (0.1 and 1.0
      micromol/l perfusion fluid) neither antagonized the ischaemic nor the reperfusion
      arrhythmias. Ischaemic arrhythmias were even intensified. Also in control hearts
      without coronary occlusion, pro-arrhythmic effects of glibenclamide were
      observed. Furthermore, the coronary flow was considerably decreased by the drug,
      and the release of adenosine and its metabolites was significantly increased.
      Sodium nitroprusside antagonized the glibenclamide-induced decrease in the
      coronary flow, but did not prevent the arrhythmias. The Ca2+ channel blocking
      agent gallopamil increased the coronary flow, decreased the adenosine release,
      and antagonized the arrhythmias in hearts with and without glibenclamide. In
      conclusion, the present findings do not favour the idea of an antiarrhythmic
      effect of glibenclamide. Rather, some propensity to the occurrence of arrhythmias
      can be produced by the drug.

PMID- 9196266
TI  - Receptor subtypes mediating spinal cardiovascular effects of angiotensin II in
      rat using losartan and PD 123319.
AB  - It has previously been shown in this laboratory that intrathecal administration
      of 10 microg of angiotensin II produces an increase in arterial pressure and
      heart rate. As two receptor subtypes of angiotensin II, termed AT1 and AT2, have
      been identified in central nervous tissue this study examines the effects of
      selective antagonists on the pressor and cardioacceleratory responses to
      intrathecal administration of 10 microg of angiotensin II to the ninth thoracic
      spinal cord. The two non-peptide antagonists were losartan (2-n-butyl-4-chloro-5
      hydroxymethyl-1-[(2'-(1H)-tetrazol-5-yl)biph enyl-4-yl)methyl]imidazole), which
      is selective for the angiotensin AT1 receptor, and PD 123319 (1-[[4
      (dimethylamino)-3-methylphenyl]methyl]-5-(diphenyacetyl)-4, 5,6,7-tetrahydro-1H
      imidazo[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate), which
      is selective for the angiotensin AT2 receptor. Intravenous administration of
      losartan blocked both pressor and cardioacceleratory effects of angiotensin II.
      Intrathecal administration of losartan blocked only the pressor effects, raising
      the possibility that block of the heart rate response was in the periphery.
      Intrathecal administration of PD 123319 blocked the pressor effect of angiotensin
      II but had no effect on the cardioacceleratory response. However, by itself the
      antagonist produced a transient increase in arterial pressure and a slower
      increase in heart rate. The data support the involvement of the angiotensin AT1
      receptor in mediating the effects of exogenously administered angiotensin II but
      also indicate a possible role of angiotensin AT2 receptors at the spinal level.

PMID- 9196268
TI  - Different regulation of myofilament Ca2+ sensitivity in beta-escin-skinned
      cardiac and vascular smooth muscles.
AB  - We compared the effects of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS, an
      activator of G-protein), phorbol 12,13-dibutylate (PDB, an activator of protein
      kinase C) and pimobendan (an inotropic agent with Ca2+-sensitizing action) on the
      Ca2+ sensitivity of the contractile proteins in beta-escin-skinned muscle
      preparations obtained from rabbit left ventricles and mesenteric arteries. After
      the skinning procedure, when GTPgammaS (100 microM) or PDB (1 microM) was added
      to the Ca2+ solutions, pCa50 were significantly increased in preparations
      obtained from vascular smooth muscle, but not from cardiac muscle, indicating
      that G-protein- and protein kinase C-mediated direct Ca2+ sensitization may occur
      only in smooth muscle, but not in cardiac muscle. In contrast, pimobendan (50
      microM) increased the Ca2+ responsiveness only in cardiac muscle. Therefore, we
      conclude that, in addition to the common regulatory factors affecting Ca2+
      sensitivity such as intracellular pH and phosphorylation by protein kinase A,
      there are other means of regulation of Ca2+ sensitivity working differently in
      cardiac and in vascular smooth muscles.

PMID- 9196269
TI  - Histamine receptors in isolated bovine oviductal arteries.
AB  - The present in vitro study was designed to evaluate the effect of histamine on
      isolated rings of bovine oviductal artery and to characterize the histamine
      receptors involved in the histamine-induced response. Endothelial dependence of
      the response was also investigated. Cumulative addition of histamine and 2
      pyridylethylamine (histamine H receptor agonist) induced a concentration
      dependent relaxation in intact arterial segments precontracted with
      noradrenaline. The histamine H1 receptor antagonist mepyramine showed non
      competitive antagonism in the histamine-induced concentration-response curve.
      However, when the response to histamine was evaluated in the presence of
      mepyramine and histamine H1 and H3 receptors were blocked, Schild analysis
      yielded a line with a slope of 1.10 and a pA2 value of 8.91, indicating simple
      competitive antagonism of mepyramine at histamine H1 receptor sites. The
      histamine H2 receptor agonist, dimaprit, caused marked dilatation only at high
      doses. Cimetidine, propranolol and mepyramine failed to inhibit this relaxant
      effect. In precontracted oviductal arteries, cimetidine did not modify the
      histamine-induced concentration-response curves. Combined treatment with
      histamine H1 and H2 receptor antagonists did not induce an additional
      displacement with respect to the isolated effect of mepyramine thus excluding
      activation of histamine H2 receptors. Histamine and (R)-alpha-methylhistamine, a
      selective histamine H3 receptor agonist, produced a moderate contractile effect
      on the resting tone of preparations. Pretreatment with the selective histamine H1
      receptor antagonist decreased the (R)-alpha-methylhistamine response but
      increased the maximal relaxant effect and abolished the contractile effect of
      histamine, suggesting the presence of a limited population of contractile
      histamine H3 receptors. Removal of the endothelium or pretreatment with methylene
      blue produced a significant inhibition of the relaxant response to histamine.
      Remaining dilatation was practically abolished by mepyramine and also by
      indomethacin. The L-arginine analogue, N(omega)-nitro-L-arginine methyl ester (L
      NAME) inhibited the effect of histamine and basal production of nitric oxide. L
      Arginine, which on its own induced significant endothelium-dependent
      vasodilatation, reversed the effect of L-NAME on histamine relaxation.
      Indomethacin only caused a slight modification of the sensitivity of the vessels
      to histamine, suggesting that prostacyclin or other cyclo-oxygenase products did
      not make a significant contribution to the model. The absence of the endothelium
      did not modify the contractile effect of histamine. The results suggest that the
      relaxant response of isolated oviductal arteries to histamine is dependent on the
      functional integrity of the endothelium and is mainly mediated by histamine H1
      receptors. These receptors may mask a minority presence of histamine H3
      contractile receptors located on smooth muscle. The main relaxing factor released
      from the endothelium by mediation of histamine is nitric oxide, which may also
      exert an effect on vascular tone.

PMID- 9196271
TI  - L-canavanine and dexamethasone attenuate endotoxin-induced suppression of
      ischaemia-reperfusion arrhythmias.
AB  - The role of inducible nitric oxide synthase in the antiarrhythmic effects of
      Escherichia coli endotoxin was examined in an anaesthetised rat model of
      myocardial ischaemia (7 min occlusion) and reperfusion (7 min) arrhythmias by
      using its specific blocker L-canavanine (100 mg/kg) and dexamethasone (5 mg/kg),
      which inhibits its expression. Endotoxin (1 mg/kg) or its solvent saline was
      administered intraperitoneally 4 h before the occlusion of the left coronary
      artery and L-canavanine or dexamethasone was administered 1 h before endotoxin or
      saline injection. The mean arterial blood pressure of rats receiving endotoxin
      was significantly lower than that of saline-treated controls, and neither L
      canavanine nor dexamethasone prevented the hypotension exerted by endotoxin.
      However, during both the occlusion and reperfusion periods, endotoxin
      significantly reduced the total number of ectopic beats (e.g., during
      reperfusion, saline: 1177 +/- 183, n = 11; endotoxin: 248 +/- 91, n = 9; P <
      0.005) and the duration of ventricular tachycardia (e.g., during occlusion,
      saline: 30.9 +/- 5.7 s; endotoxin: 1.8 +/- 0.9 s; P < 0.0001) while L-canavanine
      or dexamethasone treatment abolished the reduction exerted by endotoxin.
      Therefore we conclude that endotoxin possesses significant antiarrhythmic
      (protectant) effects in this rat model of ischaemia-reperfusion arrhythmias, and
      that its mechanism appears to involve the inducible nitric oxide synthase since
      both L-canavanine and dexamethasone inhibited this phenomenon.

PMID- 9196270
TI  - Halothane inhibits endothelium-dependent relaxation elicited by acetylcholine in
      human isolated pulmonary arteries.
AB  - This study examined whether a clinically relevant concentration of the volatile
      anaesthetic halothane modifies the endothelium-dependent relaxation produced by
      acetylcholine (3 nM-10 microM), histamine (1 pM-0.1 microM) and anti-human
      immunoglobulin E (1:1000) in human isolated pulmonary arteries submaximally
      precontracted with noradrenaline. An inhibitor of nitric oxide formation, N(G)
      nitro-L-arginine (100 microM), attenuated acetylcholine-induced relaxation but
      failed to inhibit histamine- and anti-human immunoglobulin E-induced relaxation.
      Indomethacin (2.8 microM, a cyclooxygenase inhibitor) preferentially reduced the
      relaxation to histamine and anti-human IgE. Halothane (2%) significantly
      attenuated the relaxation to acetylcholine but had no significant effect on the
      relaxation elicited by histamine and anti-human IgE. Halothane (2%) enhanced the
      basal release of prostaglandin I2 by human pulmonary arteries (control 0.31 +/-
      0.04 ng mg(-1); treated tissues 0.50 +/- 0.06 ng mg(-1); n = 5; P < 0.05).
      Halothane (2%) did not alter the responsiveness and sensitivity of preparations
      to relaxants acting through activation of adenylyl cyclase (forskolin) or
      guanylyl cyclase (sodium nitroprusside) or by the opening of K(ATP) channels
      (cromakalim). In conclusion, halothane inhibits the endothelium-dependent
      relaxation of human pulmonary arteries to acetylcholine by interfering with the
      nitric oxide pathway at a site before activation of soluble guanylyl cyclase in
      vascular smooth muscle.

PMID- 9196272
TI  - In vitro studies on the interactions of beta2-adrenoceptor agonists,
      methylxanthines, Ca2+-channel blockers, K+-channel openers and other airway
      smooth muscle relaxants in isolated guinea-pig trachea.
AB  - Pharmacodynamic interactions in vitro between different types of airway smooth
      muscle relaxants were systematically and quantitatively evaluated by using a new
      methodological technique. Relaxant concentration-effect curves for terbutaline,
      theophylline, cromakalim, sodium nitroprusside and isradipine were obtained in
      isolated guinea-pig trachea contracted by histamine (1 microM). The effects of
      three different fixed concentrations of each airway smooth muscle relaxant were
      initially attained and concentration-effect curves for combinations with
      increasing concentrations of either one of the other relaxants were produced.
      Based on pharmacodynamic parameters obtained by non-linear regression analysis of
      experimental data for the relaxants alone theoretical concentration-effect curves
      for predicted additive interaction were constructed by using the isobolic method.
      Synergistic (over-additive) interaction was defined as existing when data points
      and derived pharmacodynamic parameters obtained with combinations of the
      relaxants showed statistically significant deviation from the predicted additive
      interaction curve and its functional parameters. Significant synergistic
      interaction with terbutaline was found for both theophylline (70 or 200 microM),
      cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (30 or 100 nM) and
      isradipine (1, 3 or 10 nM). Theophylline showed synergistic interaction with
      cromakalim (0.1, 0.3 or 1 microM), sodium nitroprusside (10 nM) and isradipine
      (1, 3 or 10 nM). Interactions between cromakalim and sodium nitroprusside (10, 30
      or 100 nM) were also synergistic, whereas cromakalim and isradipine (1, 3 or 10
      nM) produced only additive interaction. Possible mechanisms underlying the
      interactions are discussed on basis of existing knowledge with special regards to
      phosphodiesterase isoenzymes, K+ and Ca2+ channels.

PMID- 9196273
TI  - In vitro and in vivo predictors of the anti-emetic activity of tachykinin NK1
      receptor antagonists.
AB  - The ability of tachykinin NK1 receptor antagonists to inhibit GR73632 (D-Ala-[L
      Pro9,Me-Leu8]substance P-(7-11))-induced foot tapping in gerbils was employed as
      an indirect measure of brain penetration and this was compared with their ability
      to prevent acute emesis induced by cisplatin in ferrets. (+)-GR203040 ((2S,3S and
      2R,3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin- 3-yl)-amine), CP
      99,994 ((2S,3S)-cis-3-(2-methoxybenzylamino)-2-phenyl piperidine)
      dihydrochloride), and L-742,694 (2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)
      phenyl-4-(5-(3-oxo-1,2, 4-triazolo)methylmorpholine) potently inhibited GR73632
      induced foot tapping (ID50 < or = 0.85 mg/kg), and acute retching induced by
      cisplatin (ID50 < or = 0.18 mg/kg). RPR100893 ((3aS,4S,7aS)-7,7-diphenyl-4-(2
      methoxyphenyl)-2-[(S)-2-(2-m ethoxyphenyl)proprionyl] perhydroisoindol-4-ol) was
      not a potent antagonist of retching (ID50 4.1 mg/kg) or foot tapping (ID50 > 10
      mg/kg). High doses (3-10 mg/kg) of CGP49823 ((2R,4S)-2-benzyl-1-(3,5
      dimethylbenzoyl)-N-[(4-quinolinyl)methyl] -4-piperineamine) dihydrochloride),
      FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-propyl]-N-methy l
      N-phenylmethyl-L-3-(2-naphthyl)-alaninamide), and LY303870 ((R)-1-[N-(2
      methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(pi peridinyl)piperidin-1
      yl)acetyl)amino]propane) were required to inhibit foot tapping; these agents were
      not anti-emetic in this dose range. SR140333 ((S)-1-[2-[3-(3,4-dichlorphenyl)-1
      (3-isopropoxyphenylacetyl)piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo
      [2.2.2]octane; 3-10 mg/kg) failed to inhibit foot tapping or emesis. Affinities
      for the human and ferret tachykinin NK1 receptor were highly correlated (r =
      0.93, P = 0.0008). Inhibition of foot tapping in gerbils, but not NK1 receptor
      binding affinity, predicted anti-emetic activity in ferrets (r = 0.75, P < 0.01).
      These findings confirm that the anti-emetic activity of tachykinin NK1 receptor
      antagonists is dependent on brain penetration.

PMID- 9196275
TI  - Nitric oxide counteracts 5-hydroxytryptamine- and cholera toxin-induced fluid
      secretion and enhances the effect of oral rehydration solution.
AB  - The effects of pharmacological modulation of the nitric oxide (NO) pathway on
      intestinal fluid transport were studied in a model of ligated jejunal loops of
      anaesthetized rats in vivo. Close intraarterial infusion of 5-hydroxytryptamine
      (5-HT) (0.16 microg/min) induced net fluid secretion. Intravenous infusion of the
      NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.55 mg/kg
      per min) reversed net fluid absorption in controls to net secretion and
      significantly enhanced 5-HT-induced fluid secretion. 5-HT-induced net fluid
      secretion was inhibited by intravenous infusion of L-arginine (8.88 mg/kg per
      min), sodium nitroprusside (22.2 microg/kg per min), or 3-morpholino sydnonimine
      (SIN-1) (22.2 microg/kg per min). Intraluminal instillation of cholera toxin (0.5
      microg/ml) induced net secretion, which was significantly enhanced by L-NAME and
      reduced by L-arginine. Another series of experiments was performed using a model
      of luminally perfused jejunal loops. Cholera toxin (10 microg/ml) induced profuse
      net fluid secretion also in this model. L-Arginine and sodium nitroprusside
      significantly enhanced net fluid absorption compared to controls and abolished
      the secretory effect of cholera toxin. Luminal perfusion with oral rehydration
      solution enhanced net absorption of fluid in controls and reversed cholera toxin
      induced secretion to absorption. Intravenous infusion, but not intraluminal
      administration, of L-arginine significantly enhanced the antisecretory effect of
      oral rehydration solution. These results give further support to the existence of
      an intestinal NO-mediated proabsorptive tone, which also downregulates fluid
      secretion elicited by different enterotoxins or mediators of secretion.
      Intravenous administration of exogenous sources of NO counteracts intestinal
      fluid accumulation and augments the antisecretory effect of oral rehydration
      solution, findings which may lead to therapeutic consequences.

PMID- 9196274
TI  - Effects of Mn2+ on the responses induced by different spasmogens in the oestrogen
      primed rat uterus.
AB  - We investigated the effect of Mn2+ on the mechanical responses evoked by high K+
      (60 mM) or low Na+ (25 mM) solutions, oxytocin and neurokinin A in the oestrogen
      primed rat uterus. In a Ca2+-free, Mn2+ (0.54 mM)-containing solution, high K+ or
      low Na+ solutions produced contractions of smaller amplitude than those observed
      in a normal Ca2+ (0.54 mM) solution, which were abolished by nifedipine (1
      microM). Oxytocin (1 microM) and neurokinin A (1 microM, in the presence of
      phosphoramidon 1 microM) evoked nifedipine-insensitive contractile responses
      similar to (oxytocin) or smaller (neurokinin A) in amplitude than those observed
      in Ca2+ (0.54 mM)-containing solution. In strips loaded with Ca2+ (2.16 mM) for
      10 min and then exposed to a Ca2+- and Mn2+-free, EGTA (3 mM)-containing medium
      for 4 min, both oxytocin and neurokinin A induced transient contraction followed
      by a small sustained response. The transient component of the response was
      abolished by cyclopiazonic acid (10 microM). When preparations were loaded with
      Mn2+ (2.16 mM) for 10 min, only the small, tonic contraction was observed. In
      Ca2+-containing solution, Mn2+ (0.01-10 mM) inhibited in a concentration
      dependent manner the rhythmic contractions developed either spontaneously or by
      electrical stimulation as well as high K+- and neurokinin A-induced contractions.
      Mn2+ also abolished the rhythmic, but not the tonic component of the response to
      oxytocin, and the preparation remained maximally contracted. These data suggest
      that in the oestrogen-primed rat uterus, Mn2+ acts as an antagonist of Ca2+
      influx through L-type voltage-operated Ca2+ channels. In addition, Mn2+ enters
      the cell mainly through nifedipine-insensitive receptor-operated channels and, to
      a lesser degree, through L-type Ca2+ channels to produce contraction by directly
      activating the contractile machinery.

PMID- 9196276
TI  - Pineal melatonin in rats: suppression by the selective alpha2-adrenoceptor
      agonist medetomidine.
AB  - This study was done to clarify the role of alpha2-adrenoceptors in the regulation
      of pineal melatonin synthesis. A selective alpha2-adrenoceptor agonist,
      medetomidine, and antagonist, atipamezole, were injected subcutaneously into rats
      and their pineal melatonin contents were measured by radioimmunoassay.
      Medetomidine (120 microg/kg) suppressed melatonin at night to a similar extent
      during the rising and descending phase of melatonin synthesis, but it did not
      affect the daytime level. A dose of 12 microg/kg was ineffective; doses of 30-180
      microg/kg suppressed nocturnal melatonin levels close to the daytime levels.
      Significant suppression was reached within 15 min and the effect started to fade
      3 h after the injection (120 microg/kg). At midday, medetomidine did not inhibit
      isoproterenol-stimulated synthesis of melatonin. Atipamezole (0.4 or 1.2 mg/kg)
      had no effect alone, but it counteracted the medetomidine-induced suppression.
      The effects of alpha2-adrenoceptor ligands on melatonin synthesis depend on the
      time of day and/or on the activity of the pineal sympathetic nerves.

PMID- 9196277
TI  - Suppression of cytokine synthesis, integrin expression and chronic inflammation
      by inhibitors of cytosolic phospholipase A2.
AB  - To define the isoform of phospholipases A2 active in inflammation we evaluated
      the effects of low-molecular-weight inhibitors of secretory and cytosolic
      phospholipases A2. We found that inhibitors of cytosolic phospholipase A2 had
      therapeutic efficacy in an in vivo model of chronic inflammation (rat adjuvant
      arthritis), whereas inhibitors of secretory phospholipase A2 had no beneficial
      effect. In vitro, inhibitors of cytosolic phospholipase A2 diminished surface
      expression of Mac-1 (CD11b/CD18) beta2-integrin on calcium ionophore-stimulated
      human blood granulocytes and suppressed synthesis of interleukin-1beta in
      lipopolysaccharide-stimulated human blood monocytes and U937 cells by reducing
      mRNA levels. Lipid mediators promote Mac-1 exocytosis and transcription of
      interleukin-1beta, which further enhances cytosolic phospholipase A2 activity and
      expression. Thus, superinduction of cytosolic phospholipase A2 may establish a
      positive feedback loop, converting acute inflammation into chronic inflammation.
      Consequently, inhibitors of cytosolic phospholipase A2 may prevent inflammation
      in vivo by interfering with cellular activation and infiltration. We conclude
      that cytosolic phospholipase A2 but not secretory phospholipase A2 is the
      predominant enzyme in inflammatory signalling.

PMID- 9196278
TI  - Effect of enkephalins and endorphins on cytotoxic activity of natural killer
      cells and macrophages/monocytes in mice.
AB  - The effect of [Met5]enkephalin, [Leu5]enkephalin, proenkephalin, dynorphin-(1-17)
      or beta-endorphin on the cytotoxic (51Cr release assay) activity of natural
      killer cells and macrophages/monocytes was studied in mice. It was found that a
      single i.p. injection of [Met5]enkephalin, [Leu5]enkephalin, beta-endorphin,
      dynorphin or proenkephalin as well as repeated treatment with both enkephalins
      increased natural killer cell activity. In vitro only [Met5]enkephalin stimulated
      natural killer cells. Opioid peptides did not affect the cytotoxic activity of
      macrophages/monocytes. In addition to functional alterations, both enkephalins
      and beta-endorphin increased the percentage of cells with natural killer
      phenotype. The results of this study suggest that the increase in natural killer
      cytotoxicity after opioid peptides injected once or for 14 days may result from
      an increased number of natural killer cells in the spleen.

PMID- 9196279
TI  - Comparative effects of nonsedating histamine H1 receptor antagonists, ebastine
      and terfenadine, on human Kv1.5 channels.
AB  - The effects of ebastine and terfenadine, long-acting nonsedating histamine H1
      receptor antagonists, were studied on hKv1.5 channels using the whole-cell
      voltage-clamp configuration of the patch-clamp technique in Ltk- cells
      transfected with the gene encoding the hKv1.5 channel. Upon depolarization to +60
      mV, terfenadine, 1 microM and 3 microM, inhibited the hKv1.5 current by 42.4 +/-
      6.4% and 69.3 +/- 4.2% (P < 0.01). In contrast, at the same range of
      concentrations, ebastine-induced inhibition of this K+ current averaged 6.5 +/-
      2.0% and 13.0 +/- 2.0 (P < 0.05). At the highest concentration tested (3 microM)
      neither terfenadine carboxylate nor carebastine significantly modified hKv1.5
      current. All these results suggest that ebastine could represent a safer
      alternative to terfenadine in the clinical practice.

PMID- 9196280
TI  - Zolpidem binding sites on the GABA(A) receptor in brain from human cirrhotic and
      non-cirrhotic alcoholics.
AB  - The displacement of [3H]flunitrazepam by unlabelled flunitrazepam or zolpidem was
      used to assess the affinity and density of sub-types of GABA(A) receptors in the
      superior frontal and primary motor cortices of ten alcoholic, seven alcoholic
      cirrhotic and ten matched control cases. The binding was best fitted by a model
      with a single site for flunitrazepam, but two sites for zolpidem. Neither the
      patients' age nor the post-mortem interval were significantly correlated with the
      affinity or density of any of the binding sites. The affinity of all ligands did
      not differ either between cortical regions or across case groups. Hence, the
      density of each binding site was analyzed at constant affinity. The densities of
      flunitrazepam and high-affinity zolpidem binding sites were invariant across
      cortical regions and case groups. Low-affinity zolpidem binding sites were
      significantly more dense in the frontal than in the motor cortex of alcoholic
      cases irrespective of cirrhosis, whereas this regional difference was not
      significant in control cases.

PMID- 9196281
TI  - Effects of clamp rise-time on rat brain IIA sodium channels in Xenopus oocytes.
AB  - The kinetic properties of wild-type rat brain IIa sodium channels in excised
      macropatches were studied using step depolarizations and ramp depolarizations to
      imitate the slow settling-time of voltage in two-electrode voltage clamp. Ramp
      depolarizations longer than 1 ms produce an increasing suppression of peak sodium
      current (I[Na]). Two rates of inactivation can be seen in macroscopic sodium
      current records from excised patches following both step and ramp
      depolarizations. During slow ramp depolarizations, reduction in peak I[Na] is
      associated with selective loss of the fastest rate of test-pulse inactivation.
      This change can be interpreted as resulting from inactivation of a separate sub
      population of 'fast mode' channels. The slow rate of test-pulse inactivation is
      relatively unaffected by changing ramp durations. These results are sufficient to
      explain the typically slow inactivation kinetics seen in two-electrode voltage
      clamp recordings of sodium channels in Xenopus oocytes. Thus, the kinetics of
      sodium channels expressed in Xenopus oocytes are not readily characterizable by
      two-electrode clamp because of the large membrane capacitance and resulting slow
      clamp settling time which artifactually selects for slow mode channels.

PMID- 9196282
TI  - A simple technique to efficiently dissociate primary auditory neurons from 5 day
      old rat cochleas.
AB  - The aim of this work was to develop a simple and reproducible method of
      dissociation of cochlear spiral ganglion neurons in the rat. This technique, wich
      was developed in 5 day-old rat pups, was based on the use of a single enzyme,
      thermolysin. It is easy to set up and allows the collection of a large amount of
      neurons. These isolated neurons were kept in a definite, serum free culture
      medium up to 7 days. Neurons were characterized both by standard morphological
      criteria and by using a specific neuronal marker (anti-neurofilament 200 kD)
      after 2 h and 7 days in culture. Cell viability, assessed by fluorescent dyes
      indicated that all isolated cells were healthy even after 7 days in vitro. The
      dissociation and culture methods were found very satisfactory and can be easily
      adapted to any kind of experiment requiring isolated spiral ganglion neurons.

PMID- 9196283
TI  - Imaging and analysis of perivascular nerves in human mesenteric and coronary
      arteries: a comparison between epi-fluorescence and confocal microscopy.
AB  - Perivascular nerves supplying human arteries can be visualised after
      immunohistochemical staining for a variety of markers. The pattern and density of
      perivascular nerves vary with region, age and disease. Quantification of the
      nerve plexus, which may be performed by image analysis, is a prerequisite to
      assess differences in nerve density. The use of epi-fluorescence microscopy (EFM)
      presents difficulties in visualising the nerve plexus in certain tissues, which
      can affect the reliability with which specific staining can be localised and
      distinguished from non-specific staining. In this study, confocal scanning laser
      microscopy (CSLM) was used in parallel with EFM, in order to compare images from
      both techniques. In a comparison of identical areas of nerve plexuses of human
      mesenteric and coronary arteries stained for protein gene product (PGP) 9.5 and
      imaged using CSLM and EFM, higher values for area percent (area occupied by
      nerves), and intercept density (ID/mm, which reflects the number of nerve bundles
      detected) were found in CSLM images. Similar comparisons of unmatched epi
      fluorescence and confocal images from a group of 45 mesenteric arteries revealed
      no significant difference for area percent, but significantly higher values for
      ID/mm in CSLM images. These findings illustrate that the better image quality in
      CSLM influences image analysis and can be very useful in studies of dynamic
      changes in nerve plexuses. We recommend CSLM for tissues that suffer from high
      background staining, such as human mesenteric and coronary arteries.

PMID- 9196285
TI  - Analysis of spatial patterns in histological sections of brain tissue.
AB  - A method is described which enables the spatial pattern of discrete objects in
      histological sections of brain tissue to be determined. The method can be applied
      to cell bodies, sections of blood vessels or the characteristic lesions which
      develop in the brain of patients with neurodegenerative disorders. The density of
      the histological feature under study is measured in a series of contiguous sample
      fields arranged in a grid or transect. Data from adjacent sample fields are added
      together to provide density data for larger field sizes. A plot of the
      variance/mean ratio (V/M) of the data versus field size reveals whether the
      objects are distributed randomly, uniformly or in clusters. If the objects are
      clustered, the analysis determines whether the clusters are randomly or regularly
      distributed and the mean size of the clusters. In addition, if two different
      histological features are clustered, the analysis can determine whether their
      clusters are in phase, out of phase or unrelated to each other. To illustrate the
      method, the spatial patterns of senile plaques and neurofibrillary tangles were
      studied in histological sections of brain tissue from patients with Alzheimer's
      disease.

PMID- 9196284
TI  - Cutaneous responsiveness of rat single motor units activated by natural
      stimulation.
AB  - Recordings of withdrawal reflexes have been used extensively to study sensory
      motor integration and processing of nociceptive information in the spinal cord.
      We describe here a new technique for the manufacture of improved EMG electrodes
      that permit the characterisation of the physiological properties of single motor
      units as well as the easy location of the muscles studied. Individual motor units
      from three rat hind-limb muscles: peroneus longus, tibialis cranialis and
      extensor digitorum longus, were activated by thermal and mechanical stimulation
      applied to their cutaneous receptive fields, which were located mainly on the 4th
      and 5th toes. Thresholds for thermal and mechanical (Von Frey hairs) stimulation
      were similar in the three muscles studied, with a value of 44 +/- 1 degrees C and
      100 mN (median), respectively. However, when a mechanical pincher with a stimulus
      area of 14 mm2 was used, the values seen were similar for peroneus longus and
      tibialis cranialis (342 +/- 23 and 330 +/- 71 mN, respectively, mean +/- S.E.M.)
      but lower for extensor digitorum longus (220 +/- 37 mN, mean +/- S.E.M.). The
      firing rate of the single motor units was similar for all types of stimulation at
      threshold intensity, and showed a linear relationship with stimulus intensity,
      except for units of the tibialis cranialis, which showed a greater degree of
      adaptation.

PMID- 9196286
TI  - A method for combining confocal and electron microscopic examination of sections
      processed for double- or triple-labelling immunocytochemistry.
AB  - Double-labelling immunocytochemical techniques are important for revealing
      synaptic connections between different populations of neurons within the central
      nervous system. This article describes a new method in which confocal laser
      scanning microscopy and electron microscopy are performed on the same Vibratome
      section which has been processed for immunocytochemistry. Two or three primary
      antibodies are initially detected with fluorescent secondary antibodies and
      observed with the confocal microscope. The primary antibodies are then revealed
      by an immunoperoxidase technique (with diaminobenzidine), and the material is
      prepared for electron microscopy. By comparing the resulting electron micrographs
      with the images acquired from the confocal microscope, it is possible to
      recognise each immunoreactive structure seen with the electron microscope in the
      original confocal images, and therefore to determine which type(s) of
      immunoreactivity each structure contains. This method has been used to
      demonstrate that some neurons in the spinal dorsal horn which possess the
      neurokinin-1 receptor receive axosomatic synapses from boutons that contain
      substance P and calcitonin gene-related peptide.

PMID- 9196287
TI  - A quantitative computer-assisted morphometric analysis of stimulation-induced
      injury to myelinated fibers in a peripheral nerve.
AB  - We describe a computer-assisted morphometric procedure for quantifying acute
      axonal injury induced in peripheral nerves by prolonged electrical stimulation.
      The procedure is a two-phase process, with the image analysis implemented via a
      commercial image analysis program, followed by an automated editing of the
      morphometric parameters of each object identified by the image analysis software.
      Both phases are implemented on IBM-compatible personal computers. The custom
      software counts the number of fibers undergoing early axonal degeneration, using
      a two-category classification scheme based on the range of myelin cross-sectional
      area and axonal cross-sectional areas of normal (unstimulated) nerves. When the
      damaged fibers are counted using this procedure, the correlation between the
      normalized amplitude of the electric stimulus and the number of degenerating
      fibers is the same as when the analysis is performed by an experienced
      histopathologist (R = 0.87) and carries the advantage of being entirely
      objective. The correlation was higher with a two-category classification
      (damage/no damage) than when the severity of the damage to each axon was weighted
      according to the amount of axonal shrinkage. We determined that axons 3.5-9
      microm in diameter are the most vulnerable to injury from the electrical
      stimulation. This has certain implications regarding the mechanism underlying
      this type of injury.

PMID- 9196288
TI  - Organotypic cultures of the rat anterior pituitary: morphology, physiology and
      cell-to-cell communication.
AB  - Organotypic cultures, prepared from young rats, were used to investigate the
      neuroendocrine properties of anterior pituitary cells. Pituitary cells maintained
      the features of endocrine cells, up to 7 weeks in vitro. Secretory granules could
      be seen with electron microscopy, and cells contained immunocytochemically
      detectable levels of adenohypophyseal hormones. Significant levels of prolactin
      (PRL), growth hormone and luteinizing hormone were present in the culture media
      after several weeks in vitro and PRL release could be modulated by dopaminergic
      agonists or forskolin. The electrophysiological properties of pituitary cells
      were investigated with both intracellular and patch-clamp recordings after 2 to 7
      weeks in vitro. Cellular resting membrane potentials were approximately -50 mV,
      and spontaneous or depolarization-induced action potentials were found in
      approximately 50% of cells. Records of voltage-dependent outward membrane
      currents showed that cells expressed functional voltage-gated channels. Cells
      remained responsive to hypothalamic neuropeptides, as shown by the outward
      membrane current triggered by thyrotropin-releasing hormone. Intracellularly
      injected Lucifer Yellow readily diffused between neighboring cells, suggesting
      the presence of gap junctions. These data confirm the viability of organotypic
      cultures of the anterior pituitary gland, and demonstrate that the characteristic
      properties of this excitable endocrine tissue are conserved. This neuroendocrine
      preparation is suitable for studying the mechanisms regulating cell-to-cell
      communication under conditions resembling the in vivo tissue organization.

PMID- 9196289
TI  - Long term chronic recordings from peripheral sensory fibers using a sieve
      electrode array.
AB  - The use of an implanted micromachined silicon sieve electrode array to make long
      term chronic recordings from the glossopharyngeal nerve is described. The implant
      consists of an array of small holes in a silicon substrate, four of which are
      surrounded by electrodes connected with an integrally fabricated ribbon cable to
      a percutaneous headcap. Using this device we have been able to monitor the
      integrity of the electrodes from the time of implantation and subsequently to
      record evoked sensory responses from mechanoreceptors on the tongue.

PMID- 9196290
TI  - PG25, a pineal-specific cDNA, cloned by differential display PCR (DDPCR) and
      rapid amplification of cDNA ends (RACE).
AB  - Synthesis of melatonin in the mammalian pineal gland is regulated by the rhythmic
      expression of acetyl-CoA: serotonin N-acetyltransferase (SNAT) and other unknown
      factors. To screen for pineal-specific mRNAs potentially involved in melatonin
      synthesis and/or regulation, differential display PCR (DDPCR) was employed. We
      used 80 primer pairs and examined 40 bands of interest. One of the pineal
      specific clones (relative to brain and eye), PG25, was studied further.
      Hybridization histochemical and Northern analyses confirmed its tissue
      specificity. The size of the corresponding mRNA is 2.4 kb. A cDNA (2 kb)
      containing the coding region was obtained using a long-template PCR-based RACE
      technique. A data base search indicates that PG25 is highly homologous to a
      recently identified human lung endothelial cell-specific gene, ESM-1.
      Interestingly, not only the amino acid sequences but also the cDNA sequences,
      including the long 3' untranslated regions, are highly similar. This suggests
      that the conserved 3' untranslated region may carry information to regulate its
      own expression. Northern analysis revealed that PG25 is also expressed in the rat
      lung, but at a much lower (10%) level compared to the pineal. Finally, our work
      shows the feasibility of a fast, integrated PCR-based cloning method for
      obtaining long, potentially full-length cDNAs with restricted expression in
      anatomically complex regions of the brain. This protocol combining several
      existing methodologies is suitable for use with limited tissue sources and uses
      minimal amounts of isotopes.

PMID- 9196291
TI  - A stereological method for estimating the total length and size of myelin fibers
      in human brain white matter.
AB  - A practically unbiased stereological method to obtain estimates of the volume and
      total length of nerve fibers in brain white matter is described. The sampling
      scheme is designed so that the majority of brain white matter is left intact,
      thus providing the possibility for resampling and further analysis. Uniform
      sampling of one complete hemispherical white matter is performed. The volume
      fraction of nerve fibers in white matter is estimated by point counting. The
      total length of nerve fibers was estimated from the product of the volume of
      white matter, obtained with the Cavalieri principle, and the fiber length
      density, obtained from the isotropic, uniform random sections which were ensured
      by the isector. The size of nerve fibers was derived by measuring the profile
      diameter perpendicular to its longest axis. The influence of the postmortem
      fixation delay on nerve fiber parameters was investigated in one dog and one pig.
      The criteria for identification of nerve fiber profiles at light microscopy were
      evaluated using electron microscopy.

PMID- 9196292
TI  - Skiing on the avalanche.

PMID- 9196293
TI  - Neonatal arterial switch operation: coronary artery patterns and coronary events.
AB  - OBJECTIVE: To determine the incidence of coronary events following neonatal
      arterial switch and to identify potential risk factors for death and coronary
      events. METHODS: The total experience (236 consecutive arterial switch
      operations) of one surgeon was studied. Associated procedures included
      ventricular septal defect closure in 37 patients (16%) and aortic arch repair in
      14 patients (6%)). The influence of various patient, procedural, support
      technique and experience variables was analyzed. RESULTS: There were 19 deaths (8
      70% confidence limits = 6-10%). Survival at 1 month, 1 year and 5 years was 93,
      92 and 92%, respectively. Risk factors for death included small birth weight (P =
      0.0015), hypoplasia of right ventricle (P < 0.0001), aortic arch obstruction (P <
      0.0001) and coronary patterns with coronary arteries coursing between the great
      arteries (P = 0.0066). Coronary events occurred in 26 patients (11-70% confidence
      limits = 9-13%) and involved coronary deaths (11 patients), non fatal myocardial
      infarctions (8 patients) and coronary stenoses or occlusions (7 patients).
      Freedom from coronary events at 1 month, 1 year and 5 years was 94, 91 and 88%,
      respectively. Risk factors for coronary events included coronary patterns with
      retropulmonary course of the left main or left circumflex coronary artery (P =
      0.0122), coronary patterns with coronary arteries coursing between the great
      arteries (P < 0.0001), all variations of intramural coronary arteries (P =
      0.0010) and commissural origin of coronary ostia (P = 0.0171). CONCLUSIONS: (1)
      In most neonates, arterial switch operation carries a low operative risk and
      provides excellent mid-term results; (2) The operative risk remains increased in
      some subsets; and (3) Some coronary patterns increase the risk of coronary
      events. Further surgical experience may improve the results.

PMID- 9196294
TI  - Increased growth factor transcription after pulmonary artery banding.
AB  - OBJECTIVE: Several mechanisms are known to produce mechanical stress during and
      after cardiac surgery, e.g. aortic cross-clamping and pulmonary artery banding
      (PAB). However, little is known about the transcription of myocardial genes which
      are changed during mechanical overload. This study was performed to investigate
      growth factor mRNA expression after PAB in porcine hearts. METHODS: The
      experiment was performed in 35 pigs (five groups). Each group consisted of three
      sham-pigs (S-pigs) and four banding-pigs (B-pigs). The mean transbanding gradient
      in B-pigs was 29 +/- 2.5 mm Hg. The hearts were excised after different time
      intervals. The probes were snap-frozen in liquid nitrogen and stored at -80
      degrees C. Analysis was performed by Northern blot. RESULTS: Right ventricular
      weight increased significantly after 7 and 24 days (P < 0.05). There was an
      upregulation of transcriptional and growth factors in B-pigs: c-jun mRNA: 412 +/-
      12.1% after 2 h (P < 0.001); c-fos mRNA: 303 +/- 18.5% after 2 h (P < 0.001);
      vascular endothelial growth factor (VEGF) mRNA: 203 +/- 18.2% after 2 h (P <
      0.001); Flk-1 mRNA: 156 +/- 16% after 2 h (P < 0.05), 253 +/- 5% after 24 h (P <
      0.01) and 184 +/- 12% after 3 days (P < 0.01); transforming growth factor-beta1
      (TGF-beta1) mRNA: 255 +/- 21.5% after 24 h (P < 0.002). Fibroblast growth factors
      1 and 2 (FGF-1 and FGF-2) were constitutively expressed in B- and S-pigs and did
      not change their expression. CONCLUSIONS: Pulmonary artery banding results in
      significant right ventricular hypertrophy and upregulation of different growth
      factors. However, growth factors known to induce hypertrophy in vitro, like the
      FGFs, showed unchanged expression. We think that myocardial growth factors may
      have trophic functions in the heart which may be useful for cardiac surgery in
      future.

PMID- 9196295
TI  - Systematic surgical closure of patent foramen ovale in selected patients with
      cerebrovascular events due to paradoxical embolism. Early results of a
      preliminary study.
AB  - OBJECTIVE: To define therapeutic strategy for management of patients with
      ischemic stroke due to a high probability of paradoxical embolism through a
      Patent Foramen Ovale (PFO). METHODS: Since 1988 all consecutive patients with
      cerebrovascular events and PFO from the Stroke Registry of our population-based
      primary-care center are prospectively studied and followed. Since 1992, among 118
      patients with cryptogenic embolic brain infarct or transient ischemic attack
      (TIA) and PFO, 32 consecutive patients younger than 60 years who presented at
      least two of the following criteria were admitted for surgery: history of
      Valsalva strain before stroke (11); multiple clinical events (13); multiple
      infarcts on brain Magnetic Resonance Imaging (MRI) (15); atrial septal aneurysm
      (ASA) (16); large right-to-left shunt (> 50 microbubbles) (12). RESULTS:
      Operative time 135' +/- 33'. CPB time 34' +/- 14'. Aortic crossclamping time 16'
      +/- 6'. Post-operative bleeding 485 +/- 170 ml. No homologous blood transfusion
      required. No neurological, cardiac or renal complications. All patients were
      followed-up corresponding to a cumulative time of 601 patient-months. This
      revealed no recurrent vascular events nor silent new brain lesions on brain MRI.
      Systematic simultaneous contrast Trans Esophageal Echocardiography (TEE)-Trans
      Cranial Doppler showed a small residual interatrial shunt in two patients.
      CONCLUSION: Surgical closure of a patent foramen ovale can be accomplished with
      very low morbidity and reduce efficiently the risk of stroke recurrence. It seems
      to be the option of choice in selected patients with a higher (> 1.5%/year) risk
      of stroke recurrence.

PMID- 9196296
TI  - Induction therapy for clinical T4 oesophageal carcinoma; a plea for continued
      surgical exploration.
AB  - OBJECTIVE: Complete resection of a locally advanced oesophageal carcinoma is not
      always feasible when invading mediastinal structures. The use of induction
      therapy prior to surgical exploration in patients with these clinical T4 tumours
      is anticipated to improve the resectability rate. METHODS: Patients, 18, who
      presented with a carcinoma of the thoracic oesophagus with clinical invasion into
      the carina (n = 6), trachea (n = 5), aorta (n = 4), lung (n = 2) and diaphragm (n
      = 1) were treated with concurrent chemotherapy and radiotherapy followed by
      surgical exploration. Follow-up was complete (mean of 17 +/- 3 months in all
      patients and 27 +/- 2 months in surviving patients). RESULTS: All patients
      completed the induction therapy with acceptable toxicity and no mortality.
      Subjective improvement in dysphagia was substantial in 11 patients (in 8/11
      patients (73%) however, there was still viable tumour in the resected specimen),
      it was minimal in six patients and absent in one patient. Objective response on
      imaging was complete in one patient, partial in eight patients and minimal in
      nine patients [in two of these nine patients (22%) nevertheless, the primary
      tumour had disappeared completely in the resected specimen (pT0)]. Resection was
      complete (R0) in 14 patients (78%) and incomplete (R1) in one patient (5%).
      Resection of the primary tumour was impossible (R2) in three patients (17%)
      because of macroscopic airway (n = 2) and hilar (n = 1) invasion on exploration.
      In these three patients the tumour was bypassed using a retrosternal split
      stomach. One patient was proven at the time of surgery to have a previously
      unidentified lung metastasis. In three patients (17%), no residual tumour cells
      were found in the resected oesophagus nor in the lymph nodes (pT0N0M0). There
      have been no in-hospital deaths. Actuarial 3 year survival was 43% in all
      patients, 55% in completely resected patients and 100% in sterilized patients
      (pT0N0M0). Median survival was 18 months in all patients. CONCLUSIONS:
      Chemo/radiotherapy followed by surgery in patients with a clinical T4 oesophageal
      carcinoma is feasible with acceptable toxicity and no treatment-related
      mortality. Operability and resectability rate were high (100 and 83%,
      respectively) compared with historical controls. The primary tumour disappeared
      completely (pT0N0-1M0-1) in 28%. Tumour sterilization rate was 17%. Survival
      looks promising compared with historical controls. Subjective neither objective
      response following induction therapy clearly correlated with the final pTNM
      staging. This indicates that, in the absence of tumour progression, neither the
      patient nor the treating physician should jeopardize the chance for ultimate cure
      by denying surgical exploration following induction therapy.

PMID- 9196297
TI  - p53, c-erbB-2 and nm23 expression have no prognostic significance in primary
      pulmonary adenocarcinoma.
AB  - OBJECTIVE: We analysed nm23, c-erbB-2 and p53 protein expression in lung
      adenocarcinoma in relation to clinicopathological status and patient survival, to
      elucidate any potential prognostic value. Published reports suggest that high p53
      and c-erbB-2 protein expression and loss of nm23 protein expression are
      associated with poor prognosis. METHODS: A total of 162 pulmonary adenocarcinomas
      resected between 1980 and 1991 were stained using monoclonal antibodies to nm23
      (NCL-nm23), c-erbB-2 (NCL-CB11) and p53 (DAKO Do7). Antigen retrieval was by
      microwave heating and bound antibody was visualised using standard
      immunohistochemical methods. Staining was scored by two observers blinded to
      tumour status and patient survival. RESULTS: Of the tumours, 101/162 (62.3%)
      exhibited high-level p53 expression, 30 (18.5%) showed high-level c-erbB-2
      membrane staining, and 77 (47.5%) demonstrated loss of nm23 positivity. The
      influence of T and N status and disease stage on postoperative survival was as
      expected. The predicted effect on patient survival of nm23, c-erbB-2 or nm23
      protein expression suggested by previous studies was not verified by our work.
      This was true both overall and for groups within the same T or N status or stage.
      CONCLUSION: Immunohistochemical assessment of the nm23, c-erbB-2 and p53 proteins
      using the above monoclonal antibodies does not have value as an independent
      prognostic indicator in pulmonary adenocarcinoma.

PMID- 9196298
TI  - War injuries of the lungs.
AB  - OBJECTIVE: The authors' experience in the treatment of war injuries of the lungs,
      gained during the war in Croatia, from August 25, 1991 until July 1, 1995, is
      presented. In that period, 424 patients with injuries of the lungs were treated
      at the Split Clinical Hospital. METHODS: The paper is a retrospective study of
      424 wounded persons with lung injuries gained during the war in Croatia,
      processed by basic statistical analysis. RESULTS: Penetrating and nonpenetrating
      wounds were present in 331 (78.1%) and 93 (21.9%) patients, respectively. There
      were 407 (96.0%) men and 17 (4.0%) women. Explosive wounds were most frequent (n
      = 251; 59.2%), followed by gunshot wounds (n = 158: 37.3%) and other types of
      wounds in 15 (3.5%) patients only. Thoracotomy was performed in 89 (22.9%)
      patients, whereas conservative surgical methods (wound treatment, chest-tube
      drainage, appropriate fluid therapy, antimicrobial and atelectasis prophylaxis)
      were used in 300 (77.1%) patients. A great majority of the patients (n = 395;
      93.2%) were discharged as fully recovered or in improved condition, 22 (5.2%)
      patients were referred to other institutions for further treatment, and seven
      (1.7%) wounded persons died. CONCLUSIONS: It is shown that most war wounds of the
      lungs can be successfully managed by 'conservative' surgical treatment.

PMID- 9196299
TI  - Early and late outcome after CABG in patients with evolving myocardial
      infarction.
AB  - OBJECTIVE: To study the determinants of early and late outcome after coronary
      artery bypass grafting (CABG) for evolving myocardial infarction. METHOD: 269
      consecutive patients underwent isolated primary or repeat CABG from 1971 to 1992
      for evolving myocardial infarction. By institutional policy, these were patients,
      strictly diagnosed, infarcting either in the cardiac cateterization laboratory,
      shortly after a previous CABG, or on cardiac intervention waiting lists. At
      operation, 125 patients were hemodynamically stable, 89 patients in cardiogenic
      shock 55 patients in cardiopulmonary resuscitation (CPR). Interval between
      infarct onset and surgical reperfusion ranged from 53 min to 15 h (median, 135
      min; 90% between 75 and 360). An internal mammary artery graft (IMA) was used in
      81 patients. Cross-sectional follow-up was 100% complete and multivariable
      analysis was conducted in the hazard function domain. RESULT: One-month, 1-year
      and 10-year survival was 86, 84 and 66%, respectively. The 1-year and 10-year
      survival, stratified by hemodynamic class, was respectively 98 and 77% for the
      stable patients, 77 and 60% for the patients in shock and 62 and 49% for those
      undergoing CPR. Shock and CPR were incremental risk factors for early but not
      late risk. Use of an IMA graft was not a risk factor early or late in either
      stable or unstable patients. CONCLUSION: CABG can be performed with acceptable
      early and long-term risk in selected patients with evolving myocardial
      infarction, whatever their hemodynamic state. Outcome as regards survival is
      neither adversely or advantageously affected by choice of bypassing conduit. An
      evolving myocardial infarction with stable hemodynamics carries a lesser risk
      than an unstable anginal state with changing ST-segment.

PMID- 9196300
TI  - Surgical angioplasty of the left main coronary artery.
AB  - OBJECTIVE: The conventional surgical treatment of isolated critical stenosis of
      the left main coronary artery (LMCA) leads to the definitive occlusion of LMCA,
      restores only a retrograde perfusion to a rather extensive myocardial area and
      consumes bypass material. Direct surgical angioplasty avoids these
      inconveniences. METHODS: Between June 1985 and August 1996, 49 surgical
      angioplasties have been performed in 47 patients. LMCA was approached posteriorly
      in the first 11 procedures, and an anterior approach was preferred in the last 38
      because of better exposure. The onlay patch consisted of saphenous vein in 37
      cases; pericardium was used in 12 cases, and only for ostial stenosis. RESULTS:
      No technical failure occurred in the last 28 cases. 44 procedures, (90%),
      succeeded, but 1 patient (2.3%) died later of a massive air embolism, and 2
      patients needed conventional CABG after 3 and 5 months, respectively. The 35
      survivors still benefiting from a successful LMCA angioplasty on the long term
      are free of ischemia after a mean follow-up of 75 months (2-136). Angiographic
      restudy was obtained in 30 patients (70%) at an average of 38 months and revealed
      an excellent result in 26 (87%). In 10 patients, a late angiographic restudy at
      an average of 71 months (32-119) still revealed a perfect result. CONCLUSION:
      Provided that well-defined contra-indications (involvement of the distal
      bifurcation, heavy calcification) are respected, LMCA surgical angioplasty
      deserves a place in the array of surgical strategies.

PMID- 9196301
TI  - Video-assisted coronary bypass surgery: clinical results.
AB  - OBJECTIVE: Clinical experience with a video-assisted coronary artery bypass
      grafting procedure using the internal mammary artery is reported. The technique
      consists of a videoscopic harvesting of the left internal mammary artery (LIMA)
      to revascularise the left anterior descending artery (LAD) through a 4-cm left
      thoracotomy. METHODS: Between September 1995 and July 1996, we performed this
      procedure on 30 patients (29 males, 1 female; aged 38-71) with an isolated
      proximal LAD stenosis (n = 21) or occlusion (n = 9). All patients were
      symptomatic despite appropriate medication. A history of non-transmural
      myocardial infarction with myocardial viability was found in nine patients.
      Fourteen patients had a restenosis after previous percutaneous transluminal
      coronary angioplasty (PTCA). Mean left ventricular ejection fraction was 0.61 (<
      0.3 in two patients). The LAD LIMA anastomosis was performed on the beating heart
      without cardiopulmonary bypass (CPB) in 26 patients. Femoral-femoral CPB was used
      in three patients because of unstable angina (n = 1) and intramyocardial LAD (n =
      2). Conversion to sternotomy and standard CPB was necessary in one patient for
      extensive endarterectomy of the LAD. RESULTS: There were no operative
      complications and no reoperations for haemorrhage. Pulmonary infection was
      observed in one patient and wound infection in one patient. Patients who
      underwent the complete procedure on the beating heart without conversion or CPB
      were ready for discharge on the 5th postoperative day (36 h-13 days). Control
      coronary angiography was performed in 20 patients. In all cases, the graft was
      patent. In 17 cases, there was a patent graft with no evidence of anastomotic
      stenosis. An occlusion of the distal segment of the LAD with a retrograde
      perfusion of the proximal segment and septal branches by the LIMA was found in
      one case. This patient was symptom-free and the stress test was negative. An
      anastomotic stenosis was noted in two patients and was treated by angioplasty (n
      = 1) or conventional surgery (n = 1). CONCLUSION: In conclusion, the efficiency
      of this minimally invasive approach should be prospectively compared with similar
      revascularisation with PTCA or surgical approaches using sternotomy with or
      without CPB.

PMID- 9196302
TI  - Coronary artery revascularisation without extracorporeal circulation. Indications
      and results.
AB  - OBJECTIVE: Coronary artery revascularisation without extracorporeal circulation
      is a technique which can be performed in selected patients in need of a coronary
      artery bypass graft. METHODS: Consecutive patients (210) underwent coronary
      artery bypass graft without extracorporeal circulation. Indications were high
      risk patients, or single coronary artery lesion. To predict perioperative
      mortality, preoperative risk factors were reviewed, and Parsonnet score was
      calculated. RESULTS: There were seven deaths (3.3%), and univariate analysis
      revealed greater age, NYHA, and poor ejection fraction to be the only predictors
      of early mortality. Perioperative myocardial infarction included 15 patients
      (7.1%), most of them seen in the multiple bypass group (10/39, 26%). Patients
      were divided into low risk (Parsonnet score < 15) 155 patients with two deaths
      (1.2%), and high risk (Parsonnet score > 15) 55 patients with five deaths (9%).
      Complete revascularisation was performed in the low risk group, while in the high
      risk only the symptomatic vessel was bypassed and other angiographic lesions
      treated with postoperative angioplasty (10 patients). A total of 12 patients
      developed early postoperative angina (5.7%), 9 presented an anastomosis
      dysfunction which was treated by angioplasty (5) and surgery (4), and 188
      patients (85.7%) did not receive transfusions while 190 patients (90.4%) did not
      need postoperative inotropes. Length of stay, operating room time, and medical
      costs were all significantly reduced. CONCLUSIONS: Myocardial revascularisation
      without extracorporeal circulation can be performed with a low operative
      mortality, and minimal morbidity only in patients undergoing single bypass
      revascularisation. It can also be performed as part of a multiple
      revascularisation strategy in association with angioplasty in high risks
      patients.

PMID- 9196303
TI  - Coronary artery bypass grafting without cardiopulmonary bypass--an attractive
      alternative in high risk patients.
AB  - OBJECTIVE: This study compares preoperative risk factors, estimated, observed,
      and risk adjusted mortality, and postoperative complications in patients
      undergoing coronary artery bypass grafting. Patients were divided in two groups
      depending on operative method: Group A patients had coronary artery bypass
      grafting using cardiopulmonary bypass. In group B cardiopulmonary bypass was not
      utilized. Patients operated on between January 1 1995 and August 31 1996 were
      compared. Group A consisted of 1829 patients and Group B 172. METHODS: Patients
      were selected to undergo coronary artery bypass grafting without the use of
      cardiopulmonary bypass either because the surgeon felt that there were
      contraindications to--or no need for the heart-lung machine. The decision to
      avoid the use of cardiopulmonary bypass was taken pre-operatively by the
      individual surgeon. Median sternotomy, formal left thoracotomy or left anterior
      small thoracotomy were used. The data was collected and validated by the
      hospital's professional data collectors. Data-analysis was performed using the NY
      state database. RESULTS: Previous heart surgery and extensively calcified
      ascending aorta were significantly more common in Group B as was estimated and
      observed mortality. This resulted in identical risk-adjusted mortality of 2.8%.
      When reoperations were reviewed separately risk adjusted mortality was lower in
      Group B (2.1 versus 3.1%) but this difference was not statistically significant.
      Cardiovascular-and other-complications were higher in group A patients. In
      reoperative patients this difference was significant (P = 0.05). The need for
      postoperative mechanical assistance was also reduced (Group A: 14.9% versus Group
      B: 1.3% P = 0.01). CONCLUSION: We conclude that coronary artery bypass surgery
      can be done safely in selected patients without cardiopulmonary bypass. Mortality
      is unchanged and complications are less frequent. Cost and hospital utilization
      are decreased. The greatest benefit is observed in reoperations.

PMID- 9196304
TI  - Minimally invasive coronary artery bypass grafting without cardiopulmonary
      bypass.
AB  - To determine the feasibility and the effectiveness of minimally invasive direct
      coronary artery bypass without cardiopulmonary bypass (MICABG) in patients with
      left anterior descending (LAD) coronary artery disease, we evaluated 90
      consecutive patients who underwent MICABG at the University Hospital of
      Groningen. PATIENTS: Between January 1995 and December 1996, 50 patients (mean
      age 60 +/- 10.3 years) with documented myocardial ischemia and isolated stenosis
      of the LAD were selected for MICABG. Patients with any associated cardiac disease
      or with acute or evolving myocardial infarction were excluded. METHODS: A small
      left antero-lateral thoracotomy in the 5th intercostal space was made in all
      patients, anastomosing the left internal mammary artery (LIMA) to the LAD. A
      short-term (3 days) postoperative rehabilitation programme was used. Emotional
      stress (STAY-DY-1 score), wound pain (VAS: visual analogue score) and O2
      saturation after a 6 min walking test were measured during hospitalisation and at
      the first follow-up examination (2.5 week after discharge). RESULTS: Mean
      operative time was 92 +/- 25 min (range 60-170). We recorded 1 (1.1%) in-hospital
      death and three cases (3.3%) of perioperative myocardial infarction. In two cases
      the MICABG was converted to the midline sternotomy. One patient underwent urgent
      reoperation on postoperative day 1 via midline sternotomy. Mean hospital stay was
      4.4 +/- 2 days. Emotional stress was significantly reduced during and after
      hospitalisation, compared with the admission day. Wound pain was mild (3.5/10
      VAS) on postoperative day 1 and reduced significantly during hospitalisation and
      at first follow-up examination. O2-saturation after a 6 min walking test had
      significantly improved at the first follow-up examination. CONCLUSION: These
      results indicate that MICABG is feasible and effective in patients with LAD
      stenosis and leads to a fast psycho-physical recovery.

PMID- 9196305
TI  - End stage coronary disease treated with the transmyocardial CO2 laser
      revascularization: a chance for the 'inoperable' patient.
AB  - OBJECTIVE: The aim of this study is to evaluate the short and mid-term efficacy
      of the Transmyocardial High Power CO2 Laser Revascularisation (TMLR) as a last
      resource method for end-stage coronary disease patients. METHOD AND PATIENTS: The
      High Power CO2 Laser 800 W Heart Laser (PLC Medical Systems) was used since
      February 1994 to treat 268 patients. In 52% of the cases (140) the indication for
      TMLR treatment was virtual inoperability by the classical bypass
      revascularisation. In the other 128 patients (48%), where only an incomplete
      revascularisation was expected, the TMLR was combined with a feasible bypass
      revascularisation (CABG). Of all patients, 71% were operated on 1-5 times before
      and or treated by several percutaneous transluminal coronary angioplasty (PTCA).
      All patients were sufferers of angina pectoris and most were classified Canadian
      Cardiac Society (CCS) 3-4, despite the maximal medical treatment. The ejection
      fraction was normal in 13% of patients only, and in 47% of them it was below 40%
      (10-68%). RESULTS: The operation itself was generally well tolerated. We lost
      only one patient at the table. The hospital survival was 89.2%; 88.2% in the
      combined group and 90.3% in the TMLR only group. After the routine follow up
      screening 3, 6 and 12 months postoperatively (262 patients--131 TMLR and 131
      TMRL/CABG), 40% of the TMLR patients upgraded into the functional class CCS 0-1;
      the combined group of patients scored up even in 84%. All considering their
      quality of life to be 'better than years ago'. The ergometry stress test,
      impossible for most of them before, became feasible and better in 80% of the
      patients. In the follow up period of the combined group, another 6 (4.7%), and in
      the TMLR only group, 12 (9.4%) patients died. CONCLUSION: The short and middle
      term results of this--until now the largest single institution series of TMLR
      treated patients--were that patients almost without exception were refused for
      any kind of surgery by several other centres; this shows an acceptable survival
      rate and a surprising level of pain relief, increased activity and better quality
      of life then ever expected. In our experience, TMLR is a suitable method for
      treatment of end stage coronary disease, if all standard measures, medical
      therapy, PTCA and redo coronary revascularisation possibilities are exhausted.
      The favourable results imply the question as to whether this method will become
      an alternative for a second bypass operation in the future. The TMLR as an
      alternative for heart transplant is already a reality for some of our patients.

PMID- 9196306
TI  - Revascularization procedures in patients with transplant coronary artery disease.
AB  - OBJECTIVE: To assess the efficacy of revascularization in cardiac transplant
      patients who developed de novo coronary artery disease. METHODS: Eighteen
      patients underwent one or more of four methods of revascularization: percutaneous
      transluminal coronary angioplasty (PTCA), percutaneous transluminal coronary
      rotational atherectomy (PTCRA), coronary artery bypass grafting (CABG), and
      transmyocardial laser revacularization (TMLR). Eleven PTCA procedures were
      performed in 10 patients 55.3 +/- 6.6 months after transplantation. Six patients
      underwent PTCRA 83.3 +/- 11.2 months after transplantation. Five patients
      underwent CABG 54.0 +/- 12.6 months after transplantation; the mean left
      ventricular ejection fraction was 49.6 +/- 16.9 (20-65%); hypertrophy was present
      in two of these patients. One patient with distal coronary artery disease and New
      York Heart Association class IV symptoms underwent TMLR only. One patient
      underwent both CABG and TMLR because of triple vessel proximal disease, diffuse
      distal disease, and New York Heart Association class IV symptoms. RESULTS: PTCA
      was successful in 10 procedures with decrease in mean stenosis from 87.7 +/- 2.7
      to 24.3 +/- 6.0%. Follow-up, at 16.9 +/- 4.0 months, showed restenosis in two
      patients. PTCRA was successful in all patients with a decrease in mean stenosis
      from 83.4 +/- 4.4 to 11.7 +/- 1.9%. Short-term follow-up did not reveal
      reocclusion. Two CABG patients who had hypertrophy died of heart failure 2 and 9
      days after their operations. One CABG patient with excellent cardiac function
      died after 15 days because of pulmonary failure. In one patient, left ventricular
      ejection fraction improved from 35 to 50%, and he is alive 64 months later. Six
      months after TMLR, the New York Heart Association class in one patient improved
      from IV to II, and his left ventricular ejection fraction improved from 29 to
      42%. The ejection fraction in the patient who underwent both CABG and TMLR
      improved from 20 to 56% but the patient expired 7 weeks later. CONCLUSIONS: It
      appears that revascularization procedures can be effective in patients with
      coronary artery disease after cardiac transplantation and that coronary
      angioplasty or atherectomy would be a therapy of choice for single proximal
      lesions. CABG should be used cautiously and only reserved for patients with multi
      vessel disease without hypertrophy. Laser revascularization with or without
      bypass grafting has potential to become the therapy of choice for transplant
      coronary artery disease.

PMID- 9196307
TI  - Donor-specific cytotoxic lymphocyte activity from bronchoalveolar lavage during
      acute canine lung allograft rejection.
AB  - OBJECTIVE: We investigated the relationship between acute lung rejection and
      donor-specific cytotoxic activity (DSCA) in recipient's lymphocytes obtained from
      bronchoalveolar lavage (BAL). METHODS: A total of 26 mongrel dogs underwent left
      lung allotransplantation. Dogs received either no immunosuppressive treatment
      (group I), cyclosporine (group II), or cyclosporine and methylprednisolone for
      evidence of acute rejection (group III). DSCA was measured by a 51Cr release
      assay, using lymphocytes from BAL samples as effector cells and 51Cr-labeled
      donor skin fibroblasts as target cells. The pathologic findings of the
      transplanted lungs were classified according to the working formulation for
      classification and grading of pulmonary rejection. In addition, the degree of
      cellular infiltration in the perivascular, peribronchial, interstitial, and
      intraalveolar areas was determined based on an infiltration score. RESULTS: DSCA
      in BAL samples was elevated during mild, moderate and severe acute rejection. The
      accuracy of the diagnosis of mild or moderate rejection was 92.3% at
      effector:target (E:T) ratios of 100:1 and 50:1. The DSCA in the BAL fluid and the
      total infiltration score were correlated closely with correlation coefficients of
      0.859 and 0.828 at E:T ratios of 100:1 in group I and group II dogs,
      respectively. Lung aeration improved and DSCA decreased with methylprednisolone
      therapy in three of four dogs with grade 2 rejection. CONCLUSION: There is a
      direct relationship between the DSCA in BAL fluid and the degree of tissue damage
      caused by acute rejection. The DSCA can be detected by a 51Cr release assay which
      may hold promise for future clinical applications.

PMID- 9196308
TI  - The pulmonary homograft as aortic valve substitute: 7 years' follow up.
AB  - OBJECTIVE: The advantages of the aortic valve homograft high resistance to
      infective endocarditis, low risk of thromboembolism, low gradient and excellent
      long term results are well known. Trying to extend these advantages to a greater
      number of patients, we used pulmonary homografts as aortic valve substitute,
      based on the experimental evidence, that they can withstand the higher stress in
      systemic circulation. METHODS: From September 1988 to August 1994 175 patients
      (103 men, 72 women, mean age 61.75 +/- 12.92 years) underwent aortic valve
      replacement with a cryopreserved pulmonary homograft. All valves were taken from
      our own homograft bank. They were inserted freehand intraaortically, 162 in
      subcoronary position, 13 as intraaortic cylinder. All patients were followed
      clinically and by colorflow Doppler echocardiography in 3-12 month intervals.
      RESULTS: Patients, 8, died perioperatively (4.57%). None of the deaths was valve
      related. Patients, 2, had to be reoperated during the perioperative period due to
      severe valvular incompetence 165 patients were followed up to a period of 7.5
      years (mean interval 3.83 +/- 1.45 years). Patients, 30, died, 13 deaths (7.42%)
      must be regarded as valve related. Patients, 22, (12.52%) had to be reoperated
      due to severe graft incompetence. Patients, 9 (5.14%), acquired prosthetic
      endocarditis. CONCLUSION: Due to our results, high rate of valve related deaths,
      high rate of graft failure and high rate of prosthetic endocarditis, we must
      state that the pulmonary homograft did not fulfil our expectations and presently
      we can not recommend it as an aortic valve substitute.

PMID- 9196309
TI  - Stentless porcine bioprostheses for all types of aortic root pathology.
AB  - OBJECTIVE: Conventional biological and mechanical prostheses have important
      limitations with regard to their results concerning thrombosis, hemorrhage and
      long-term durability. Aortic valve replacement with stentless devices results in
      superior hemodynamic function because obstructing stents and sewing rims are
      avoided. In addition, no anticoagulation therapy is needed. METHODS: From 1 June
      1991 until 31 May 1996, 235 patients received aortic valve replacement with
      stentless aortic porcine bioprostheses. Patients' ages ranged from 24 to 88 years
      (mean 64 years). In 21.3% of all patients, concomitant procedures were performed.
      Coronary artery bypass graft (CABG) and mitral valve surgical therapy were the
      most frequent ones (31 and 12 cases, respectively). Implanted valve sizes ranged
      from 21 to 29 mm in diameter. RESULTS: A total of 122 patients received a
      subcoronary implantation with the lower row performed with interrupted stitches
      and the upper row with a continuous suture. In 99 cases we performed the
      inclusion cylinder technique, also with lower interrupted sutures and running
      upper sutures after adaptation of the coronary ostia into the graft. In the group
      with small aortic roots, the total root replacement technique (n = 14) was used.
      Mortality at 30 days was 4.7% (11/235). Echocardiography at discharge
      postoperatively revealed a mean gradient across the prosthesis of 6 mm Hg. Color
      Doppler suggested no or trivial regurgitation in 93% of all examined patients and
      mild regurgitation without clinical symptoms in 7%. Up to now, 98.2% of all
      discharged patients have been free of valve-related reoperation. CONCLUSIONS:
      With implantation of stentless bioprostheses, an improved hemodynamic function
      will be obtained. Almost every aortic root pathology can be safely treated with
      any of the techniques described. The short and intermediate results seem to be at
      least equal to any other prostheses or treatment methods. The long-term
      performance of these devices is still under investigation.

PMID- 9196310
TI  - Survival and cause of death after mitral valve replacement in patients aged 80
      years and over: collective results from the UK heart valve registry.
AB  - OBJECTIVE: Over the last decade there has been an increasing number of patients
      aged 80 years and over undergoing heart valve replacement. However, literature on
      the outcome of mitral valve replacement (MVR) in this age group is still limited.
      METHODS: We conducted the present study by analysing data extracted from the UK
      Heart Valve Registry. From January 1986 to December 1994, 86 patients underwent
      isolated MVR and 10 underwent combined MVR with aortic valve replacement (AVR)
      and were reported to the Registry. RESULTS: The 30 day mortality was 10.4% (9/86)
      in the MVR group and 10% (1/10) in the MVR and AVR group. The actuarial survival
      was 79.8, 64.1 and 40.7% at 1, 3 and 5 years, respectively, in the MVR group. Of
      the 10 early (30 day) deaths, 8 were due to cardiac reasons and 19 of the 28 late
      deaths were due to non-cardiac reasons. A total of 55 (57.2%) patients received a
      bioprosthetic valve implant and 41 (42.8%) patients received a mechanical valve
      implant. There was no difference in survival between the two groups. CONCLUSIONS:
      The above results suggest that MVR in octogenarians produces a satisfactory early
      postoperative outcome and moderate medium-term benefit. There is no difference in
      survival between patients receiving bioprosthetic and patients receiving
      mechanical valve implants.

PMID- 9196311
TI  - Influence of age on valve related events with Carpentier-Edwards pericardial
      bioprosthesis.
AB  - Age is the most important factor for the durability of biological valves. With an
      original design the Carpentier-Edwards pericardial valve showed improved results
      at 10 years. The influence of age on valve related complications is studied with
      a 10 year follow up on 807 valvular replacements. METHODS: Between January 1984
      and December 1993, 807 patients underwent valve replacements with a Carpentier
      Edwards pericardial bioprosthesis. Patients, 193 were younger than 60 years, 284
      between 60 and 70 years and 330 patients were older than 70 years. All patients
      but seven were followed up for an average of 4.18 years after their operation and
      total follow up was 3373 patient years. Patients were divided into three groups
      of age: group I, less than 60 years; group II, 60-70 years; group III, over 70
      years. A retrospective comparison was made between age groups. RESULTS: At 11
      years, valve related complications included 97 patients with 27 valve related
      deaths. Rates of valve related death increase with age linearized rate were 0.3,
      0.6 and 1.2%, respectively. No difference was observed for rates of all valve
      related morbidity: 2.6, 2.4 and 3.5%, respectively. Risk of thromboembolism
      increased with age, linearized rates were: 0.3, 0.7 and 1.3%. Risk of
      deterioration and reoperation decreased with age, rates of deterioration were
      0.8, 0.1 and 0%. Other valve related events had the same incidence in all groups.
      No statistical difference was observed between group II and group III for
      deteriorations and reoperations. CONCLUSIONS: The performance of the Carpentier
      Edwards pericardial valve is the same at 10 years in group II and III. This study
      supports the clinical use of this tissue valve in patients over 60 years. The
      results in group I are satisfactory, nevertheless, a more durable biological
      valve is needed for young patients.

PMID- 9196312
TI  - Self management of oral anticoagulant therapy after heart valve replacement.
AB  - OBJECTIVE: Patients with mechanical heart valves require lifelong oral
      anticoagulant treatment which entails frequent blood sampling and dosage
      adjustment. The purpose of this study was to investigate the feasibility of
      letting heart valve operated patients manage blood specimen analysis and dosage
      adjustment themselves. METHODS: A total of 21 patients were enrolled in the study
      and followed for at least 9 months postoperatively. Immediately after the heart
      valve operation they were trained in operating a CoaguChek international normal
      ratio (INR) monitor to analyze capillary whole blood samples. Subsequently
      training in dosage adjustment was accomplished and all patients were considered
      fully capable of self management after 30 weeks. In the training period, parallel
      laboratory INR measurements were made at 3-4 week intervals for reference. A
      control group of 20 patients was matched, respectively, to the study group. The
      INR target range was 2.0-3.0. RESULTS: Out of the 21 study patients 19 continued
      self management beyond 9 months. The median INR value obtained with the monitor
      was within therapeutic target range for all study patients and only 15 out of 20
      control patients were within this range. The mean systematic deviation between
      laboratory and CoaguChek INR was 7.8% but each patient had a constant
      characteristic deviation from -11 to +21%. The study patients were within
      therapeutic target range 77% of the time compared with 53% for the control
      patients. CONCLUSIONS: Self management of oral anticoagulation is feasible for
      selected patients and constitutes a significant service improvement compared with
      conventional management. The CoaguChek monitor seems sufficiently accurate and
      reliable for self testing and the treatment quality is comparable or even better
      than conventional management. Assessment of the rate of bleeding and thrombo
      embolic events shall be settled in studies comprising larger number of patients.

PMID- 9196313
TI  - Growth potential of aortic autografts and allografts: effects of cryopreservation
      and immunosuppression in an experimental model.
AB  - OBJECTIVE: An animal model has been used to evaluate the potential of growth of
      vascular autografts and allografts, and the effects of cryopreservation,
      rejection and immunosuppression on this growth. METHODS: In 35 animals (seven
      groups of five female NZW rabbits; age 5-6 weeks; weight 1.1 kg), a graft
      interposition was performed at the level of the infrarenal aorta. Different
      groups included fresh autografts, fresh and cryopreserved consanguineous
      allografts (donor: litter sister), fresh and cryopreserved immunosuppressed (IS)
      consanguineous allografts (receiving cyclosporin 10 mg/kg per day) and fresh and
      cryopreserved allografts. Animals were allowed to grow normally and were
      sacrificed at the mean weight of 2.89 kg. We studied the growth of the native
      aorta and of the graft and calculated the growth ratio (growth of the
      graft/growth of native vessel). Grafts and adjacent aorta were histologically
      studied. RESULTS: Growth of the graft was normal (mean ratio 1.08; S.D. = 0.21)
      for autografts, and for fresh and cryopreserved IS consanguineous grafts. Growth
      was absent (mean ratio 0.12; S.D. = 0.15) for fresh and cryopreserved allografts
      (P = 0.0001). In consanguineous grafts without IS, growth was absent or normal,
      presumably according to genetic compatibility, but never intermediate.
      Histological study showed normal optic microscopic aspects when growth was normal
      and, when growth was absent, aspects compatible with rejection including mainly
      intimal hyperplasia and medial thinning. CONCLUSIONS: (1) Normal growth of
      arterial autografts was confirmed; (2) cryopreservation did not prevent potential
      growth of an arterial graft; and (3) in an allogenic situation, without IS, an
      aortic graft, fresh or cryopreserved, never showed any growth potential.

PMID- 9196314
TI  - Long-term results of patch repair for saccular aneurysms of the transverse aortic
      arch.
AB  - OBJECTIVE: Long-term results of patch repair in patients with a saccular aneurysm
      of the aortic arch were investigated. PATIENTS: From December 1984, 43 patients
      with a saccular aneurysm of the arch underwent patch repair. Indications for
      patch repair were determined as orifice diameter of aneurysm being less than 1/3
      of the total circumference of the aorta. METHOD: Midsternotomy was used in 38
      patients, and left thoracotomy in five. Selective cerebral perfusion was used in
      28 patients, deep hypothermic circulatory arrest with retrograde cerebral
      perfusion in eight during the last 3 years, and partial cardiopulmonary bypass in
      seven. RESULTS: There were five (11.6%) early deaths, and causes were respiratory
      failure in two patients, low cardiac output in two, and gastrointestinal bleeding
      in one. Stroke was found in three patients (6.9%). During follow-up, seven
      patients died, two due to rupture of a residual or pseudoaneurysm, one due to
      reoperation of pseudoaneurysm, one due to stroke, two due to respiratory failure,
      and one due to unknown cause. Postoperative survival, including early death, was
      69.3% at 5 years and 43.3% at 9 years. Aortic reoperation was done in three
      patients with a pseudoaneurysm formation and two survived. Freedom from
      reoperation was 91.7% at 5 years and 38.2% at 9 years. Event free ratio was 79.3
      +/- 9.8% at 5 years and 37.6 +/- 18.6% at 9 years. CONCLUSION: Because of a high
      incidence of pseudoaneurysm or residual aneurysms after patch repair for a
      saccular aneurysm of the aortic arch, strict criteria for the patch repair should
      be applied or graft replacement of the aorta is recommended.

PMID- 9196315
TI  - Clinical effects of the heparin coated surface in cardiopulmonary bypass.
AB  - OBJECTIVE: In a randomised study of 120 patients, undergoing primary operation
      for coronary heart decease, two groups were investigated as regards to the
      effects of heparin coated cardiopulmonary bypass on brain function parameters and
      general clinical outcome. The study group (n = 56) was perfused using an extra
      corporeal circuit treated with covalent bonded heparin; the control group (n =
      59) used an identical set-up without heparin treatment. Systemic heparin doses
      were calculated to achieve ACT levels of 250 and 500 s, respectively.
      Postoperative course was evaluated by examining a set of clinically relevant
      parameters including a detailed registry of postoperative deviations. Brain
      function was assessed by the biochemical marker S-100 and tests of memory
      performance. RESULTS: There were several signs of reduced operative trauma in the
      study group. Hospital stay was reduced by nearly 1 day (P < 0.05). Time on
      postoperative ventilatory support was approximately 4 h shorter (P = 0.009).
      Chest drain blood loss was decreased both at 8 (P = 0.01) and 24 h (P = 0.007)
      postoperatively. Body temperature was lower after surgery and especially on days
      2 (P = 0.03) and 3 (P = 0.01). Perioperative creatinine elevation was
      significantly reduced (P = 0.03). Neurological deviations were fewer (P = 0.01).
      Brain function assessment revealed reduced plasma levels of S-100 both at
      termination of cardiopulmonary bypass (P = 0.008) and 7 h later (P = 0.04).
      However, no remediation of memory impairment could be demonstrated. CONCLUSIONS:
      Cardiopulmonary bypass with covalent bonded heparin attached to the extra
      corporeal circuit in combination with a reduced systemic heparin dose seems to
      reduce safely and effectively the operative stress to the patient. There were
      also signs of improved cerebral protection.

PMID- 9196316
TI  - Circulatory support with paracorporeal pneumatic ventricular assist device (VAD)
      in infants and children.
AB  - OBJECTIVE: The feasibility and efficacy of the pneumatic 'Berlin Heart'
      ventricular assist device (VAD) were evaluated in 14 pediatric patients with
      profound cardiogenic shock refractory to conventional therapy. METHODS: There
      were two patient groups. Eleven patients, aged 2 weeks 15 years and weighing 3.2
      52 kg received a left ventricular assist device or a biventricular assist device
      as a bridge to cardiac transplantation (bridge group). Nine of them had liver,
      kidney, or lung dysfunction before device implantation. Three patients were
      supported with a biventricular assist device for myocardial recovery (recovery
      group): a 6-month-old girl for postcardiotomy shock, a 10-month-old girl for
      allograft failure after cardiac transplantation, and a 4-year-old boy with acute
      myocarditis. RESULTS: In the bridge group, eight patients were transplanted after
      a bridge duration of 6-98 days (mean, 32 days) with five long-term survivors.
      Organ functions were normalized during bridging in all of the transplant
      recipients. In the recovery group, the first patient was removed from support
      after 2 days because of irreversible brain damage. The second patient was weaned
      from biventricular support after 8 days, but suffered from recurrent allograft
      failure. The third patient received biventricular support for 21 days followed by
      extracorporeal membrane oxygenation and was subsequently discharged from the
      hospital. CONCLUSIONS: The 'Berlin Heart' VAD can keep selected infants and
      children with life-threatening heart failure for weeks or months.

PMID- 9196317
TI  - Direct visualization of leukocyte/endothelial cell interaction during
      extracorporeal circulation (ECC) in a new animal model.
AB  - OBJECTIVE: The clinical complications of extracorporeal circulation (ECC) have
      been linked to a systemic activation of cellular and humoral components and to a
      dysregulation of the microcirculatory compartment. Since to date only in vitro
      methods exist for evaluation, we developed an animal model to study the effects
      of ECC on the microcirculation. To establish the model, we assessed whether these
      effects are dependent on the duration of ECC. METHODS: Intravital fluorescence
      microscopy was used on the dorsal skinfold chamber preparation in chronically
      instrumented, awake Syrian golden hamsters. ECC was realized using a micro
      rollerpump and a silicon tube shunting blood between the carotid artery and the
      jugular vein. ECC was performed in three groups for various times (2, 10 and 20
      min) after application of heparin at 300 IU/kg body wt. In hamsters, the
      application of high-dose heparin releases endothelial bound superoxide dismutase
      (SOD), a natural scavenger of oxygen-derived free radicals. Protocol II assigned
      two groups receiving heparin at different doses of 50 and 2000 IU/kg body wt.
      RESULTS: ECC for 2 min served as control to exclude effects from hemodilution and
      resulted in a minimal induction of leukocyte/endothelial cell interaction.
      Isovolemic ECC for 20 min resulted in an increase in rolling (from 11 +/- 3 to 38
      +/- 20%, mean +/- S.D., P < 0.05) and adherent leukocytes (from 19 +/- 16 to 215
      +/- 145 cells/mm2, mean +/- S.D., P < 0.05) in postcapillary venules.
      Microhemodynamic parameters and functional capillary density were not
      significantly affected. Arterial blood pressure and heart rate were stable.
      Heparin at 2000 IU/kg inhibited post-ECC leukocyte adhesion following ECC,
      whereas 50 IU/kg showed no protective effects. CONCLUSIONS: Leukocyte/endothelial
      cell interaction, induced by blood contact with synthetic surfaces, was directly
      visualized in vivo. The number of adherent leukocytes was dependent on the
      duration of ECC. The application of high-dose heparin followed by release of SOD
      almost prevented leukocyte activation, suggesting a formation of oxygen free
      radicals during ECC. The new application of the hamster model may allow to study
      the underlying pathomechanisms and to develop therapeutic/prophylactic strategies
      to avert problems associated with ECC.

PMID- 9196319
TI  - An improved valve rotator.
AB  - A device to rotate valve prostheses is described. By using a polythene tubing
      universal joint the valve may be turned by twisting the handle of the valve
      rotator without altering its spatial orientation. This modification was designed
      to facilitate what can be a frustrating manoeuvre and should be applicable to any
      rotatable valve.

PMID- 9196318
TI  - Inhibition of endogenous endothelin during cardioplegia improves low coronary
      reflow following prolonged hypothermic arrest.
AB  - OBJECTIVE: Endothelin-1 (ET) is a potent endogenous vasoconstrictor which has
      been shown to be increased following ischaemia and cardiopulmonary bypass. We
      tested the hypothesis that inhibition of ET synthesis during cardioplegic arrest
      using phosphoramidon (an ET converting enzyme inhibitor) or blockade of ET
      receptors using bosentan (a mixed ET(A)/ET(B) antagonist), might improve the
      postischaemic recovery of coronary flow. METHODS: Using an isolated Langendorff
      perfused rat heart model we compared the addition of phosphoramidon or bosentan
      to St Thomas' Hospital No. cardioplegia vs. control (plain cardioplegia). We
      measured recovery of coronary flow following 4 h of cardioplegic arrest at 4
      degrees C. In a second series of experiments using an isolated working rat heart
      model we measured the recovery of cardiac function following 4 h of cardioplegic
      arrest at 4 degrees C. Results are expressed as percentages of preischaemic
      values (+/- S.E.M). RESULTS: In the first series of experiments, addition of
      phosphoramidon to cardioplegia improved the postischaemic recovery of coronary
      flow after 30 min of reperfusion: control 81.3% (+/- 3.5); phosphoramidon 10(-6)
      M 86.2% (+/- 3.1); phosphoramidon 10(-5) M 95.0% (+/- 3.0) P = 0.03 vs. control.
      Likewise, addition of bosentan 10(-5) M improved coronary flow following 20 min
      of reperfusion: control 96.7% (+/- 4.0), and bosentan 109.6% (+/- 4.7) P = 0.04.
      The addition of phosphoramidon or bosentan had no effect on the postischaemic
      recovery of mechanical function following 30 min of reperfusion. CONCLUSION: Both
      inhibition of ET synthesis and ET receptor blockade during prolonged hypothermic
      arrest improves postischaemic coronary flow, but appears to have no effect on the
      recovery of cardiac mechanical function.

PMID- 9196320
TI  - Repair of late left ventricular rupture after repeat mitral valve replacement.
AB  - Late rupture of the left ventricle after repeat MVR was successfully repaired by
      patch closure through the right atrium. We recommend early elective repair of
      such lesions before cardiac function is compromised.

PMID- 9196321
TI  - Aorto-pulmonary fistula: a rare event in the evolution of a dissecting aneurysm
      of the thoracic aorta.
AB  - The natural history of a thoracic aneurysm is usually towards the dissection or
      free rupture; rarely an aorto-pulmonary fistula can complicate this lesion. We
      present two cases of Aorto-pulmonary fistula as acute complication of an aneurysm
      of thoracic aorta; the etiopathology seem to be related to the same mechanism: a
      dissecting aneurysm of the ascending aorta leading to a secondary fistulation in
      the main pulmonary artery. In our two cases the diagnosis was suggested by
      clinical findings and by Doppler-echocardiography. Both patients were managed
      surgically with success and both survived.

PMID- 9196323
TI  - Abdominal arterial conduits for CABG and GI complications.

PMID- 9196322
TI  - Reoperations after dacron patch aortoplasty with heparinized femoro-femoral
      bypass.
AB  - Dacron patch aortoplasty used to be a standard therapy in some surgical units.
      Occurrence of aneurysm formation after this procedure is well known. The
      incidence of aneurysms is reported to be 0-35% with a high risk of lethal
      rupture. We report three cases of aneurysm repair of the descending thoracic
      aorta after dacron patch aortoplasty using femoro-femoral extracorporeal system.
      Heparin-coated system was used primarily to prevent ischemic spinal cord injury
      through hypotension of the distal aorta and secondarily to reduce the risk of
      intraoperative hemorrhage.

PMID- 9196324
TI  - Antagonism within and around the organizer: BMP inhibitors in vertebrate body
      patterning.

PMID- 9196325
TI  - T-box family reunion.

PMID- 9196326
TI  - Genetic dissection of the function of mammalian P-glycoproteins.
AB  - Mammalian P-glycoproteins are plasma membrane proteins belonging to the
      superfamily of ATP-binding cassette transporters. They were discovered as drug
      pumps in multidrug-resistant cancer cells, but are also present in many normal
      tissues. Genetic approaches have helped to dissect the physiological functions
      and mode of action of P-glycoproteins. Disruption of both genes for the drug
      transporting P-glycoproteins in mice has no effect on the normal sheltered life
      of these mice, but renders them hypersensitive to many drugs. P-glycoprotein
      appears to be especially important in protecting the brain and in limiting uptake
      of hydrophobic drugs from the gut. Recent experiments with polarized cells
      support the idea that drug-transporting P-glycoproteins act by flipping drugs
      from the inner to the outer leaflet of the plasma membrane.

PMID- 9196327
TI  - Facing death in the fly: genetic analysis of apoptosis in Drosophila.
AB  - Apoptosis, a gene-directed form of cell death, occurs normally during development
      and plays a major role in many diseases, including cancer and neurodegenerative
      disorders. Molecular genetic studies in Drosophila have revealed the existence of
      three novel apoptotic activators, reaper, head involution defective and grim.
      Additionally, Drosophila homologs of evolutionarily conserved IAPs (inhibitor of
      apoptosis proteins) and CED-3/ICE-like proteases have been identified and
      characterized. Through the combined use of genetic, molecular, biochemical and
      cell biological techniques in Drosophila it should now be possible to elucidate
      the precise mechanism by which apoptosis occurs, and how the death program is
      activated in response to many distinct death-inducing signals.

PMID- 9196328
TI  - Frontiers in keratodermas: pushing the envelope.
AB  - A clinically and genetically heterogeneous group of disorders, known collectively
      as the palmoplantar keratodermas, are unified by the phenotypic characteristic of
      a thickening of the skin over the palms and soles. Although spectacular progress
      has been made in understanding the basis of many genodermatoses, the genetic
      defects causing many of the keratodermas are still largely unknown. These unusual
      phenotypes are beginning to capture the attention of investigators in epidermal
      biology, and several compelling lines of evidence point to the cornified cell
      envelope and structural components of the desmosome as potential underlying
      targets of disease. It is anticipated that understanding the molecular basis of
      the keratodermas will underscore the importance of the integrity of the cell
      envelope and the desmosome, and provide new insights into the mechanisms of
      epidermal differentiation and related disorders.

PMID- 9196329
TI  - The genetic analysis of multiple sclerosis.
AB  - Although monogenic diseases often show extreme clinical phenotypes, the major
      burden of genetic ill health lies in the more prevalent polygenic disorders, such
      as diabetes, hypertension and multiple sclerosis. These conditions affect many
      thousands of individuals and their management consumes vast amounts of health
      care resources: in the UK some 80,000 people have multiple sclerosis; the
      estimated financial cost to society of introducing treatments, such as beta
      interferon, could be as high as 250 million pounds per year. Knowledge on the
      genetics of these common diseases is poor, but has potentially received a
      considerable boost with the arrival of whole genome screening. The genome screen
      in insulin-dependent diabetes mellitus (IDDM) reported in 1994 was the first in a
      human polygenic disease. Since this publication, whole genome screening has been
      performed in a variety of human polygenic diseases, including schizophrenia,
      bipolar affective disorder, non-insulin-dependent diabetes mellitus (NIDDM),
      inflammatory bowel disease, asthma and multiple sclerosis.

PMID- 9196330
TI  - Strand asymmetries in DNA evolution.
AB  - The complementary strands of DNA differ with respect to replication and
      transcription. Both of these processes are asymmetric and can bias the occurrence
      of mutations between the strands: during replication, the discontinuous lagging
      strand undergoes certain errors at higher rates, and transcription overexposes
      the nontranscribed strand to DNA damage while targeting repair enzymes to the
      transcribed strand. While biases introduced during replication apparently have
      little impact on sequence evolution, the effects of transcription are observed in
      the asymmetric patterns of substitution in bacterial genes and might be
      influencing genome-wide patterns of base composition.

PMID- 9196331
TI  - Yeast's clickable chromosomes and other genome browsers.

PMID- 9196332
TI  - It's a knockout!

PMID- 9196333
TI  - National hospital discharge survey: annual summary, 1994.
AB  - OBJECTIVES: This report presents national estimates of the use of non-Federal
      short-stay hospitals in the United States during 1994. Estimates are provided by
      demographic characteristics of patients discharged, geographic region of
      hospitals, conditions diagnosed, and surgical and nonsurgical procedures
      performed. Measurements of hospital use include number and rate of discharges and
      days of care, and the average length of stay. METHODS: The estimates are based on
      data collected through the National Hospital Discharge Survey for 1994. The
      survey has been conducted annually by the National Center for Health Statistics
      since 1965. In the 1994, data were collected for approximately 277,000
      discharges. Of the 512 eligible non-Federal short-stay hospitals, 478 (93
      percent) responded to the survey. Diagnoses and procedures are presented
      according to their code number in the International Classification of Diseases,
      9th Revision, Clinical Modification, or ICD-9-CM. RESULTS: In 1994 there were an
      estimated 30.8 million discharges from non-Federal short-stay hospitals. These
      patients used a total of 177.2 million days of care and had an average length of
      stay of 5.7 days. Other data summarized in this report include estimates for
      diagnoses, procedures, expected source of payment, hospital deaths, and newborn
      infants.

PMID- 9196334
TI  - Hazards from surgical gloves.

PMID- 9196335
TI  - Neo-intimal hyperplasia in vascular grafts and its implications for autologous
      arterial grafting.
AB  - With the advent of modern microsurgical procedures and an improved understanding
      of the cellular dynamics of vascular graft adaptation, arterial grafts are being
      used more frequently in surgical practice. In this article the structure and
      development of neointimal hyperplasia in vascular grafts, both venous and
      arterial, are reviewed briefly. The underlying biology of venous graft adaptation
      is now well understood. However, in addition to venous grafts, many different
      arterial conduits are now being used; these include the radial artery, internal
      mammary (thoracic) and gastroepiploic arteries. The different clinical outcomes
      of these arterial grafts and the underlying cell biology of their adaptation to
      the grafted environment are also reviewed.

PMID- 9196337
TI  - Management of small fragment wounds in modern warfare: a return to Hunterian
      principles?

PMID- 9196336
TI  - Rapid prototyping techniques for anatomical modelling in medicine.
AB  - The rapid advances in computer technology, often driven by the demands of
      industry, have created new possibilities in surgery which previous generations of
      surgeons could only have imagined. Improved imaging with computerised tomography
      (CT) has been followed by magnetic resonance imaging (MRI) and, more recently, it
      has become possible to reformat the data as three-dimensional images. Computer
      technology has new moved forward with the advent of rapid prototyping techniques
      (RPT) which allow both the production of models of the hard tissues and custom
      made prostheses from computerised scanning data. In this article we review the
      development and current technologies available in RPT and the applications of
      this advance in surgery and illustrate this with two case reports.

PMID- 9196338
TI  - Bacterial translocation in surgical patients.

PMID- 9196339
TI  - Current practice in pharyngeal pouch surgery in England and Wales.
AB  - A survey of the current surgical practice for patients with a pharyngeal pouch
      was conducted among general surgeons, otolaryngologists and cardiothoracic
      surgeons in England and Wales. Our results show that while pouch excision remains
      the most common method used, endoscopic stapling diverticulotomy is rapidly being
      adopted. The reasons why this recently introduced technique is likely to become
      the definitive treatment of pharyngeal pouch are discussed.

PMID- 9196340
TI  - Management of penetrating injuries of the cervical trachea.
AB  - This is a report of a 2-year experience with the management of penetrating injury
      of the cervical trachea. There were 29 cases. The respiratory status of the
      patient on admission dominated the initial management: 12 patients required
      emergency intubation and were immediately taken to operation, while 17 patients
      were more stable and could be subjected to the preoperative assessment of the
      oesophagus. Associated injuries were significant and dominated the postoperative
      morbidity and mortality. Primary repair of the trachea, without tracheostomy, was
      successful in a relatively high proportion of patients (55%).

PMID- 9196341
TI  - Role of fine needle aspiration cytology in the management of the discrete parotid
      lump.
AB  - A review of fine needle aspiration cytology (FNAC) indicates that the technique
      can distinguish benign from malignant parotid, disease in 93% of patients
      evaluated. However, a surgery of 34 head and neck oncologists revealed that
      making this distinction when an apparently benign parotid lump was being
      investigated did not normally alter the surgical management for in the presence
      of low-grade cancer survival is not improved with radical surgery. As FNAC does
      not alter treatment of a discrete parotid lump, no consensus is currently
      possible regarding its most appropriate use. Perhaps its value is as a screening
      procedure and to provide a little more information when advising the patient.

PMID- 9196342
TI  - A prospective evaluation of the modified Alvarado score for acute appendicitis in
      children.
AB  - The accuracy of the modified Alvarado score was assessed prospectively in the
      preoperative diagnosis of acute appendicitis in children. A consecutive series of
      118 patients (54 boys, 64 girls) with acute abdominal pain was studied
      prospectively over a 6 month period. Appendicitis was confirmed in 38 of 43
      children undergoing appendicectomy, giving a false-positive appendicectomy rate
      of 11.6%. No child under active observation was subsequently found to have a
      perforated appendix. The overall sensitivity of a modified Alvarado score of > or
      = 7 was 76.3% and its specificity was 78.8%. Current clinical practice is more
      accurate than the modified Alvarado score in the diagnosis of acute appendicitis
      in children.

PMID- 9196343
TI  - Surgeons' follow-up practice after resection of colorectal cancer.
AB  - Consultant surgeons in two United Kingdom Health Regions were invited to complete
      a questionnaire on details of their personal management of patients with colon
      and rectal cancer, with particular emphasis on follow-up. Replies from 140 (94%)
      were analysed by the surgeon's subspecialty of colorectal and gastrointestinal
      surgery (group 1) and all others (group 2). There was a wide variation in the
      duration of followup, but no difference between the two groups. More group 1
      surgeons carried out investigations as a routine after colonic (P < 0.01) and
      rectal (P < 0.01) resection. Colonoscopy was used more frequently by group 1 (P <
      0.0001) and barium enema by group 2 surgeons (P < 0.05). Investigations to detect
      asymptomatic metastases were used as a routine by 33.3% of surgeons, in whom
      there was no concordance over the choice or combination of tests and no
      difference between the two groups of surgeons. There is no consensus among
      surgeons as to the ideal duration, intensity and method of follow-up after
      resection for colorectal cancer and little difference between the practice of
      colorectal and gastrointestinal surgeons and that of other specialists, except in
      the use of colonoscopy and barium enema. These results reflect the continuing
      lack of evidence on which to base the follow-up of patients after surgery for
      colorectal cancer.

PMID- 9196344
TI  - Frozen shoulder: unravelling the enigma.

PMID- 9196345
TI  - Ionising radiation: are orthopaedic surgeons' offspring at risk?
AB  - The hazards of exposure to ionising radiation are well documented. Fears have
      been raised that occupational exposure to ionising radiation by orthopaedic
      surgeons may have detrimental effects on the future health of their unborn
      offspring. The current members of the British Orthopaedic Trainees' Association
      and orthopaedic consultants appointed during the last 5 years in the United
      Kingdom were contacted using a postal questionnaire. Obstetricians and
      gynaecologists of a similar age group were also contacted to act as the control
      group. The collected data were compared with the latest national data as
      published by the Office of Population Censuses and Surveys for England and Wales
      (OPCS, 1991). In all, 504 questionnaires were posted to orthopaedic surgeons and
      1597 to obstetricians and gynaecologists. Reply rates were 334 (66%) and 986
      (62%), respectively. Our data reveal a higher rate of congenital abnormalities as
      compared with the normal population in both groups (P < 0.001). However, there
      were no statistically significant differences in the rate of congenital
      abnormalities between the offspring of orthopaedic surgeons and obstetricians and
      gynaecologists (P = 0.78). These findings suggest that the increased rate of
      congenital abnormalities observed in both groups is more likely to be associated
      with factors other than exposure to X-rays. In this study, male surgeons had a
      higher incidence of female children compared with the normal population (P =
      0.01). The incidence of childhood malignancies does not appear to be raised in
      either group. These findings suggest that the current levels of occupational
      exposure to X-rays by orthopaedic surgeons is unlikely to be associated with an
      increased risk of congenital abnormalities or childhood malignancies in their
      children.

PMID- 9196346
TI  - Influence of fine-bore catheter length on infusion thrombophlebitis in peripheral
      intravenous nutrition: a randomised controlled trial.
AB  - Previous studies indicated that the risk of thrombophlebitis associated with
      continuous infusion of intravenous nutrition (IVN) via peripheral veins was
      reduced when fine-bore catheters, inserted to 15 cm, were used in place of
      standard intravenous cannulas. An explanation has not been identified, but may be
      owing to the greater length of the catheters. A randomised controlled study was
      performed in which a standard nutritional solution was infused via 22G
      polyurethane catheters inserted to a length of either 5 cm or 15 cm. Catheters
      were reviewed twice each day and removed when complications occurred, or when IVN
      was no longer required. There was no significant difference in median time to
      thrombophlebitis or extravasation, or in daily risk of thrombophlebitis, between
      insertion lengths. Survival proportions were similar for each length at all
      times. Catheters inserted into cephalic veins were more prone to thrombophlebitis
      or extravasation (nine episodes, 14 catheters) than catheters inserted into
      basilic veins (five episodes, 24 catheters, P = 0.009). The survival proportion
      was at all times greater when catheter tips lay in basilic veins. Thus, the risk
      of thrombophlebitis or extravasation was not influenced by the length of catheter
      within the vein. However, the vein in which the catheter tip lay appeared to
      influence the development of morbidity.

PMID- 9196347
TI  - The qualities and conduct of an English surgeon in 1446: as described in a
      manuscript attributed to Thomas Morstede.
AB  - The year 1996 marks the 550th Anniversary of an anonymous manuscript which
      represents one of the earliest surgical works written in English. Generally
      attributed to Thomas Morstede, Serjeant-Surgeon to King Henry V, the book was for
      many centuries considered to have been lost and has escaped detailed examination
      by the surgeons of today. We present a modern translation of its first chapter in
      which the author outlines the range of equipment a fifteenth-century surgeon
      would use, the personal qualities all surgeons should possess, and the manner in
      which surgical practice should be conducted.

PMID- 9196348
TI  - False aneurysm of an intercostal artery after thoracoscopic sympathectomy.

PMID- 9196349
TI  - Gallstone ileus without a gallbladder.

PMID- 9196350
TI  - Breast incisions for conservation surgery.

PMID- 9196351
TI  - Video-assisted thoracoscopy in the evaluation of penetrating thoracic trauma.

PMID- 9196352
TI  - Head injury--abuse or accident?

PMID- 9196353
TI  - Transsphenoidal surgery for pituitary tumours.
AB  - OBJECTIVES: Transsphenoidal surgery (TSS) is the preferred method for the
      excision of pituitary microadenomas in adults. This study was carried out to
      establish the long term efficacy and safety of TSS in children. STUDY DESIGN: A
      14 year retrospective analysis was carried out on 23 children (16 boys and seven
      girls), all less than 18 years of age, who had undergone TSS at our centre.
      RESULTS: Twenty nine transsphenoidal surgical procedures were carried out. The
      most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting
      adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range
      0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No
      death was related to the operation. The most common postoperative complication
      was diabetes insipidus, which was transient in most patients. Other complications
      were headaches in two patients and cerebrospinal fluid leaks in two patients. De
      novo endocrine deficiencies after TSS in children were as follows: three (14%)
      patients developed panhypopituitarism, eight (73%) developed growth hormone
      insufficiency, three (14%) developed secondary hypothyroidism, and four (21%)
      developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five
      (24%) patients, though all patients received postoperative glucocorticoid
      treatment until dynamic pituitary tests were performed three months after TSS.
      CONCLUSIONS: TSS in children is a safe and effective treatment for pituitary
      tumours, provided it is performed by surgeons with considerable experience and
      expertise. Surgical complications are minimal. Postoperative endocrine deficit is
      considerable, but is only permanent in a small proportion of patients.

PMID- 9196354
TI  - Adrenal function and high dose inhaled corticosteroids for asthma.
AB  - OBJECTIVE: To investigate effects on adrenal function of fluticasone, a recently
      released inhaled steroid preparation with lower systemic bioavailability than
      beclomethasone dipropionate. METHODS: 34 children on high doses (400-909
      micrograms/m2/d) of inhaled beclomethasone dipropionate or budesonide were
      recruited into a double blind, crossover study investigating the effects on
      adrenal function of beclomethasone and fluticasone propionate, given using a
      standard spacer (Volumatic). The 24 hour excretion rates of total cortisol and
      cortisol metabolites were determined at baseline (after a two week run in), after
      six weeks treatment with an equal dose of beclomethasone, and after six weeks of
      treatment with half the dose of fluticasone, both given through a spacer device.
      RESULTS: The comparison of effects between fluticasone and beclomethasone during
      treatment periods, although favouring fluticasone in all measured variables,
      reached significance only after correction for urinary creatinine excretion
      (tetrahydrocortisol and 5 alpha-tetrahydrocortisol geometric means: 424 v 341
      micrograms/m2/d). The baseline data showed adrenal suppression in the children
      taking beclomethasone (total cortisol geometric means: 975 v 1542 micrograms/d)
      and a dose related suppression in the children taking budesonide. Suppressed
      adrenal function in the children who were taking beclomethasone at baseline
      subsequently improved with fluticasone and beclomethasone during treatment
      periods. CONCLUSIONS: Fluticasone is less likely to suppress adrenal function
      than beclomethasone at therapeutically equivalent doses. The baseline data also
      support the claim that spacer devices should be used for the administration of
      high doses of inhaled topical steroids.

PMID- 9196356
TI  - Relation between dietary fat and energy and micronutrient intakes.
AB  - Concern has been raised about the energy and nutrient adequacy of low fat diets
      for children that aim to prevent cardiovascular disease in Western populations.
      The diets of 174 randomly chosen schoolchildren aged 8-12 years from middle and
      high socioeconomic groups were analysed to determine their nutrient composition
      in relation to fat intake. The mean percentages of energy intake from fat and
      saturated fat were 31 and 13%, respectively, and 44% of all children reported
      consuming < 30% of their energy from fat. The energy intake did not change across
      the spectrum of fat intake. A decreased fat intake was associated with an
      increased sugar intake, but also with increased nutrient densities of thiamin,
      niacin, folate, vitamin C, magnesium, and iron, reflecting an increased intake of
      fruit, vegetables, and grains. Parental educational level was the most important
      determinant of fat intake (inverse relation). It is concluded that a self
      selected low fat intake among children from average to high socioeconomic
      backgrounds does not compromise their intake of major nutrients or energy.

PMID- 9196355
TI  - Audit of screening programme for congenital hypothyroidism in Scotland 1979-93.
AB  - OBJECTIVE: To evaluate the efficiency of the screening programme for congenital
      hypothyroidism in Scotland and to determine the outcome in the cohort of children
      with positive testing for thyroid stimulating hormone (TSH). DESIGN:
      Establishment of comprehensive database for all Scottish infants with high TSH,
      detected on Guthrie screening. SUBJECTS: 344 infants born between August 1979 and
      December 1993 with TSH greater than 40 mU/l on initial Guthrie, or 15-40 mU/l on
      repeat Guthrie. MAIN OUTCOME MEASURES: Ages at time of: (a) Guthrie collection,
      (b) notification of positive result by laboratory, and (c) start of treatment;
      audit of late diagnosis/missed cases; categorisation of positive cases into
      definite and probable congenital hypothyroidism, transient TSH elevation, and
      uncertain status; educational status of children with definite and probable
      congenital hypothyroidism. RESULTS: 344 positive cases were categorised as having
      definite (224) and probable (11) congenital hypothyroidism, transient TSH
      elevation (88), and status uncertain (21). The overall incidence of
      definite/probable congenital hypothyroidism was 1 in 4400 live births. For the
      definite/probable groups median age of Guthrie collection was consistently
      between 6 and 7 days from 1983 onwards but for the whole cohort was later than 10
      days in 10.5%. Median age of notification fell from 14 days in 1980 to 11 days in
      1993. Median age of starting treatment ranged between 11 and 15 days from 1983
      onwards. Treatment was delayed in four cases, three due to failed or late Guthrie
      card submission. Of 149 children with definite/ probable congenital
      hypothyroidism who were of school age, educational status was ascertained in 139
      (93%). Only two children (1.4%) were attending special school, one of whom was
      known to have mild hypothyroidism. Sixteen children (11.5%) were receiving extra
      help in mainstream education compared with 18% of control children in the
      Scottish very low birth weight study. CONCLUSION: The current screening programme
      is working well, but efficiency could be increased by earlier and more reliable
      Guthrie collection. A substantial proportion of children picked up on the
      screening programme have a transient rise in TSH rather than true congenital
      hypothyroidism. The incidence of special education and learning support in
      Scottish children with congenital hypothyroidism appears to be no different to
      that of the general population.

PMID- 9196357
TI  - Developmental quotient at 24 months and fatty acid composition of diet in early
      infancy: a follow up study.
AB  - AIM: A follow up study of developmental quotient (DQ) at 24 months of toddlers
      whose diets in early infancy differed in fatty acid composition, and in whom an
      association between diet and DQ was observed at 4 months. METHODS: 81 toddlers
      were distributed among three groups according to early type of diets standard
      infant formula (SFo, n = 30); long chain polyunsaturated fatty acid (LC-PUFA)
      enriched formula (LCPFo, n = 26); human milk (HM, n = 25). DQ at 24 months was
      assessed by Brunet-Lexine's psychomotor developmental test. A subgroup (n = 20;
      SFo 8; LCPFo 6; HM 6) was tested for erythrocyte phosphatidyicholine and
      phosphatidylethanolamine. RESULTS: No DQ differences were found by analysis of
      variance. Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were
      predictors of DQ scores at 24 months. Phosphatidylcholine arachidonic and
      docosahexaenoic acid correlated positively, and phosphatidylcholine linoleic acid
      and phosphatidylethanolamine eicosapentaenoic acid negatively, with DQ. Multiple
      regression analysis including these variables explained 52% of inter-individual
      DQ variance. A strong association was found between the erythrocyte
      phosphatidylcholine arachidonic/ linoleic acid ratio and DQ (r = 0.75; p =
      0.0001). CONCLUSIONS: The diet/DQ association found at 4 months was not
      predictive of DQ scores at 24 months. Irrespective of dietary or genetic factors,
      there appears to be a strong correlation between the LC-PUFA composition of the
      red cell membrane and higher neurodevelopmental performance.

PMID- 9196358
TI  - Gastrointestinal handling of [1-13C]palmitic acid in healthy controls and
      patients with cystic fibrosis.
AB  - AIM: To examine the gastrointestinal handling of [1-13C]palmitic acid given as
      the free acid by measuring the excretion of 13C label in stool in 16 healthy
      children and 11 patients with cystic fibrosis on their habitual enzyme
      replacement treatment. METHODS: After an overnight fast, each child ingested 10
      mg/kg body weight [1-13C]palmitic acid with a standardised test meal of low
      natural 13C abundance. A stool sample was collected before the test and all
      stools were collected thereafter for a period of up to five days. The total
      enrichment of 13C in stool and the species bearing the 13C label was measured
      using isotope ratio mass spectrometry. RESULTS: The proportion of administered
      13C label excreted in stool was 24.0% (range 10.7-64.9%) in healthy children and
      only 4.4% (range 1.2-11.6%) in cystic fibrosis patients. The enrichment of 13C in
      stool was primarily restricted to the species consumed by the subjects (that is
      as palmitic acid). CONCLUSIONS: There does not appear to be a specific defect in
      the absorption of [1-13C]palmitic acid in patients with cystic fibrosis. The
      reasons why cystic fibrosis patients appear to absorb more of this saturated
      fatty acid than healthy children is not clear and requires further investigation.

PMID- 9196359
TI  - Computed tomography in chronic inflammatory bowel disease.
AB  - In children with complicated inflammatory bowel disease, conventional ultrasound
      imaging may not define the extent of extraluminal disease and the involvement of
      other viscera. Three children with chronic inflammatory bowel disease are
      presented, where computed tomography was well tolerated and provided valuable
      information on extraluminal disease, involvement of other organs, and the state
      of the bowel wall and mesentery. In children in whom ultrasound examination is
      inconclusive or limited by gas or tenderness, computed tomography can provide
      important information that may determine clinical management.

PMID- 9196360
TI  - Urinary antimony in infancy.
AB  - OBJECTIVE: To determine whether antimony may be detected in the urine during
      infancy and early childhood and its association with passive exposure to tobacco
      smoke, as assessed by urinary cotinine. DESIGN: Analysis of spare aliquots of
      urine collected from infants participating in studies of respiratory function and
      passive smoking. Urinary antimony was assayed using inductively coupled plasma
      mass spectroscopy in 201 urine specimens collected at different ages throughout
      the first two years of life from 122 term and 26 preterm infants. Urinary
      cotinine was measured using gas liquid chromatography. MAIN OUTCOME MEASURE:
      Urinary antimony concentrations. RESULTS: Absolute antimony concentrations varied
      widely between infants, being below the laboratory detection limit of 0.02
      microgram/l in 7% of samples, below 0.5 microgram/l in 90.5%, and above the
      reference value of 1 microgram/l reported for non-occupationally exposed UK
      populations in 4%. Creatinine standardised antimony values were unrelated to
      postnatal age or urinary cotinine concentrations and were highest in urine
      collected from preterm infants within 24 hours of birth (geometric mean (95%
      confidence interval): 2.3 ng/mg (1.5 to 3.4)). CONCLUSIONS: Although antimony is
      present at very low concentrations in urine during infancy and early childhood,
      the relevance to health is uncertain. The higher levels found in preterm infants
      may reflect prematurity or fetal assimilation of antimony. Tobacco is unlikely to
      be an important source of environmental exposure to antimony during infancy and
      early childhood.

PMID- 9196361
TI  - Nutritional impact of antipseudomonas intravenous antibiotic courses in cystic
      fibrosis.
AB  - OBJECTIVE: To evaluate the short term effects on nutritional status of home
      intravenous anti-pseudomonas antibiotic courses in cystic fibrosis (CF) patients
      chronically colonised with Pseudomonas aeruginosa. DESIGN: A prospective study
      involving 38 CF patients, mean age 10.9 (SD 4.3) years (range 4.3 to 22.2 years),
      presenting with pulmonary exacerbations of P aeruginosa infection. The patients
      received a 14 day antibiotic course of intravenous ceftazidime (200 mg/kg/day)
      and either amikacin (35 mg/kg/day) or tobramycin (15 mg/kg/day). Nutritional
      evaluation on days 1 and 14 involved measurements of weight, weight/height ratio
      (per cent of predicted value), energy intake (per cent of recommended daily
      allowances), serum prealbumin, and body composition assessed by two methods:
      bioelectrical analysis (BIA) and skinfold anthropometry. The non-parametric
      Wilcoxon t test was used for statistical analysis, with a Bland-Altman plot to
      assess the degree of agreement between the two methods of evaluating body
      composition. RESULTS: Weight increased by 1.0 (0.8) kg (p < 0.001); weight/height
      increased from 94.4(12.2)% to 98(12.7)% (p < 0.001), energy intake from 107(32)%
      to 119(41)% (p < 0.02), and prealbumin from 183 (63) to 276 (89) mg/l (p <
      0.001). Fat mass increased by 0.8 (1.0) kg (p < 0.001), without any significant
      change in fat-free mass. The limits of agreement between BIA and anthropometry
      were -0.7 kg and +1.1 kg. CONCLUSIONS: Antibiotic courses allow an improvement in
      nutritional status in CF patients, with a gain in fat mass.

PMID- 9196362
TI  - Prolidase deficiency and systemic lupus erythematosus.
AB  - Two children with prolidase deficiency, an inborn error of proline metabolism,
      developed clinical and immunological abnormalities consistent with a diagnosis of
      systemic lupus erythematosus (SLE). The first child died from septicaemia, and
      SLE was only diagnosed during his terminal illness. As a result of this diagnosis
      his cousin, who was already known to have prolidase deficiency, was investigated
      further and a diagnosis of SLE confirmed. Following treatment with oral
      prednisolone her clinical condition has improved, although she has a persistently
      raised erythrocyte sedimentation rate (ESR) and florid facial rash. Both
      prolidase deficiency and SLE are associated with disturbances in immune function
      and have clinical features in common. It is likely that prolidase deficiency is a
      risk factor for the development of SLE. Additionally, patients with SLE should
      where there is a family history or presentation in childhood-be specifically
      investigated for prolidase deficiency, since standard immunological or
      haematological investigations will not identify the characteristic biochemical
      abnormalities.

PMID- 9196363
TI  - Continuous midazolam infusion as treatment of status epilepticus.
AB  - In a tertiary referral centre, midazolam infusion was tried as treatment for 20
      children with status epilepticus over a period of two years. The mean age of the
      children was 4.07 years. Twelve children with refractory status epilepticus had
      received intravenous or per rectal diazepam and intravenous phenytoin/
      phenobarbitone or both before midazolam was given (0.15 mg/kg bolus followed by 1
      5 micrograms/kg/min infusion). Eight children required only midazolam to control
      the established status epilepticus. The seizures were controlled in 19 children.
      The mean time required for complete cessation of seizures was 0.9 hours. The mean
      infusion rate required was 2.0 micrograms/kg/min. All children had regained full
      consciousness by a mean of 5.1 hours after discontinuation of midazolam
      treatment. No metabolic derangement or compromise of vital functions was noted in
      any of the children. Midazolam infusion is thus an effective and safe therapeutic
      approach for the management of childhood status epilepticus.

PMID- 9196364
TI  - Retinal haemorrhages and convulsions.
AB  - AIMS: To evaluate the incidence of retinal haemorrhages after convulsions in
      children. PATIENTS AND METHODS: All children who required hospital admission
      after an episode of convulsions were included in the study. Complete neurological
      and ocular examinations, including ophthalmoscopy, were undertaken within 48
      hours of hospital admission. RESULTS: Thirty three children were examined
      according to the protocol and their seizures were classified by a paediatric
      neurologist. Despite the fact that some of the children also vomited or underwent
      cardiopulmonary resuscitation, none of the 33 children developed retinal
      haemorrhages. CONCLUSIONS: Convulsions rarely (if ever) give rise to retinal
      haemorrhages. The finding of retinal haemorrhages should stimulate a detailed
      assessment to exclude non-accidental injury, whatever the nature of the
      associated or antecedent events.

PMID- 9196365
TI  - Predictive value of a 24 hour tuberculin skin test evaluation.
AB  - The predictive value of induration 24 hours after administration of purified
      protein derivative (PPD) was examined. Altogether 1082 healthy schoolchildren
      were tested using 5 tuberculin units of PPD. Induration was measured at 24, 48,
      and 72 hours. At 24 hours, induration of any size had a relatively low positive
      predictive value (63%), although indurations > 5 mm had a higher (86%) positive
      predictive value.

PMID- 9196366
TI  - Hypertension secondary to progressive vascular neurofibromatosis.
AB  - A 4 year old girl with neurofibromatosis type 1 (NF1) was referred for
      hypertension. An aortogram showed narrowing of the left main renal artery. An
      angiogram three and a half years later showed coarctation of the abdominal aorta.
      She underwent aortoplasty but the stenosis recurred. Vascular involvement in NF1
      may be progressive and requires long term follow up.

PMID- 9196368
TI  - Subglottic haemangioma.
AB  - OBJECTIVES: To describe experience with subglottic haemangioma in a unit where
      conservative treatment has been favoured. METHODS: Retrospective case note review
      of infants presenting with subglottic haemangioma over a 25 year period. RESULTS:
      Thirty one infants were identified. Diagnosis was difficult where skin
      haemangiomas were absent and where the lesion was circumferential rather than
      asymmetrical. Tracheostomy was safe, well tolerated, and managed by the patients'
      family at home. Major complications were seen only when laser treatment was used.
      CONCLUSIONS: Aggressive treatment with substantial risks of long term
      complications may not be necessary in this spontaneously resolving disorder.

PMID- 9196367
TI  - Congenital total lipodystrophy and peripheral pulmonary artery stenosis.
AB  - Multiple peripheral pulmonary artery stenoses were detected in three patients
      with congenital generalised lipodystrophy. This association, which has not been
      described before, may be clinically important in patients with lipodystrophy who
      present with impaired exercise tolerance or heart murmurs.

PMID- 9196369
TI  - Management of childhood arthritis. Part 1: Acute arthritis.

PMID- 9196371
TI  - Ambulatory paediatrics--making a difference.

PMID- 9196370
TI  - Poverty and the health of children and adolescents.

PMID- 9196372
TI  - Guarding paediatricians against allegations of assault.

PMID- 9196373
TI  - Altruism under fire.

PMID- 9196374
TI  - Sleeping metabolic rate in infants.

PMID- 9196375
TI  - Childhood cancer in schools with a radioactive lightning rod.

PMID- 9196376
TI  - Acknowledgments and authors.

PMID- 9196377
TI  - Potassium and sodium dependent glucose transport: implications for cystic
      fibrosis.

PMID- 9196378
TI  - Focal abnormalities detected by 18FDG PET in epileptic encephalopathies.

PMID- 9196379
TI  - Sp1- and octamer-consensus sequence binding proteins during lens fibre
      differentiation.
AB  - The pattern of factors binding to either the Sp1-consensus sequence or to the
      octamer sequence during in vitro rat lens fibre cell differentiation has been
      examined by electrophoretic mobility shift assays. With the Sp1-consensus
      sequence as probe, two major and four minor bands were seen. Three bands were
      present at all stages of differentiation, two are lost during terminal
      differentiation and one is present only in late differentiating cells. The
      octamer probe yielded three bands, which co-migrate with Oct2, Oct3 and Oct7. The
      exact identity of these factors has not been established. The Oct3-like band was
      detected only in epithelial cell extracts, the other two bands were also found in
      fibre cell extracts, whereby the intensity of the Oct2-like band decreased
      relative to that of the Oct7-like band during differentiation. In transfection
      studies, a rat gamma D-crystallin promoter in which the proximal activator has
      been replaced by a dimer of the Sp1-consensus sequence showed a gradual increase
      in activity with differentiation, in contrast, a similar construct with an
      octamer dimer was active only during late differentiation and mimicked the
      pattern of activation of the parental gamma D-crystallin promoter.

PMID- 9196380
TI  - Corneal hyaluronan content during post-ablation healing: evidence for a transient
      depth-dependent contralateral effect.
AB  - The hyaluronan content during wound healing following excimer laser photoablation
      was investigated. Rabbit corneas were photoablated (Summit Omnimed, 193 nm, 5 mm
      diameter, 50 microns and 100 microns depth). Central optical zones of
      photoablated and contralateral corneas were removed 7, 30 and 90 days after
      surgery. Corneas from 2 untreated rabbits were used as control. Hyaluronan
      content was determined after pepsin-solubilization using an alkaline-phosphatase
      linked hyaluronectin sorbent assay. The hyaluronan content of non-photoablated
      contralateral corneas was significantly increased and the changes appeared depth
      dependent. Hyaluronan content returned to control levels by the first month at 50
      microns depth and by the third month at 100 microns depth in contralateral
      corneas. The hyaluronan content of the photoablated corneas was not significantly
      different from that of the non-photoablated contralateral sample regardless of
      the depth of photoablation. By contrast, the hyaluronan content of the treated
      corneas was significantly higher than that of the controls during the first month
      post-surgery and returned to control values by the third month. Thus the
      hyaluronan contents in the photoablated and contralateral corneas after excimer
      laser corneal photoablation were very similar during wound healing. This study
      shows that excimer laser photoablation induced transient depth-dependent
      contralateral alterations of the hyaluronan content.

PMID- 9196381
TI  - The effect of systemic nitric oxide-synthase inhibition on ocular fundus
      pulsations in man.
AB  - There is experimental evidence that endothelium derived nitric oxide is involved
      in the regulation of ocular vascular tone. The purpose of this study was to
      investigate the effects of NO-synthase inhibition by N-monomethyl-L-arginine (L
      NMMA) on ocular fundus pulsations in young healthy volunteers. Three milligrams
      per kilograms L-NMMA were administered i.v. over 5 minutes. Protocol 1:
      Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO
      exhalation, and cardiac output were performed at baseline and 10, 30, 60, 90,
      150, and 300 minutes after L-NMMA infusion (n = 8). Fundus pulsation amplitude,
      which has been shown to estimate the pulsatile component of the choroidal blood
      flow, was recorded with a recently developed laser interferometer. Protocol 2:
      Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO
      exhalation, and blood flow velocity in the ophthalmic artery were performed in a
      randomized, placebo controlled cross over study (n = 10). Ten minutes after L
      NMMA administration fundus pulsation amplitude decreased by 23 +/- 2% (protocol
      1) and 19 +/- 1% (protocol 2, P < 0.01 each), cardiac output by 12 +/- 2% (P <
      0.01), and exhaled NO by 55 +/- 6% (protocol 1) and 41 +/- 6% (protocol 2, P <
      0.01 each). All parameters returned to baseline values within the 300 minutes
      observation period, with a faster recovery of fundus pulsation amplitude than of
      cardiac output and exhaled NO. Blood pressure, pulse rate, and ophthalmic artery
      blood flow velocity showed only minor changes during and after administration of
      L-NMMA. Our results suggest that systemic NO-synthase inhibition reduces
      pulsatile choroidal and most likely total choroidal blood flow in humans. The
      recovery of vascular tone in choroidal vessels seems to be different from the
      cardiovascular response. Our findings indicate that reduced fundus pulsations
      after L-NMMA are caused by systemic factors as well as by local reactions of the
      choroidal vasculature.

PMID- 9196382
TI  - A model membrane system to investigate antioxidants in bovine rod outer segments.
AB  - The antioxidant activities of compounds endogenous to bovine rod outer segments
      (ROS) were investigated by measuring the loss of polyunsaturated fatty acids
      (PUFA's) from membranes exposed to the water-soluble oxidant 2,2'-azobis(2
      amidinopropane) dihydrochloride (AAPH). Osmotically intact ROS, ROS membranes,
      and unilamellar liposomes prepared from ROS phospholipids (PL) were compared.
      Intact ROS were most resistant to oxidative loss of PUFA's, followed by ROS
      membranes and then PL liposomes. The development of a model membrane system
      allowed the investigation of putative antioxidants singly and in combination.
      These lipid-soluble compounds were incorporated into PL liposomes, and it was
      found that normal physiological concentrations of alpha-tocopherol (vitamin E)
      and free fatty acids (16:0, 18:0, 18:1, 22:6) significantly decreased oxidative
      loss of PUFA's. When all the major free fatty acids were added to PL liposomes at
      the same concentrations found when ROS phospholipase A is stimulated, the
      oxidative loss of PUFA's was reduced by 31%. The antioxidant effect of free fatty
      acids suggests that endogenous phospholipase A's may act to protect membranes by
      releasing esterified fatty acids in proportions and concentrations that afford
      protection to membrane lipids.

PMID- 9196383
TI  - Expression of integrin receptors on plasma membranes of primary corneal
      epithelial cells is matrix specific.
AB  - Modulation of cell behavior may occur through cell adhesion receptors that bind
      domains of extracellular matrix molecules and mediate cell-substrate signal
      transduction. It was hypothesized that while primary corneal epithelial cells
      seeded onto laminin and fibronectin express and synthesize integrin receptors,
      they are not detected on the plasma membrane until the appropriate ligand is
      present. The integrin subunits (alpha-6, beta-4 and beta-1) present on the plasma
      membrane after adherence to laminin and fibronectin were compared with changes
      that occurred in mRNA expression and protein synthesis. Prior to seeding, the
      percentage of cells expressing integrin receptors and matrix proteins on their
      plasma membrane was determined. Negligible laminin and fibronectin (0-7%) were
      present on the plasma membrane while the population of epithelial cells
      expressing beta-4 and beta-1 on the plasma membrane was low (21-23%). After 3 hr
      of adherence the cell population expressing integrin subunits was substrate
      dependent. The percentage of cells adherent to LM expressing beta-4 was four-fold
      greater than cells adherent to FN. After 24 hr the percentage of cells cultured
      on fibronectin expressing beta-4 increased significantly indicating ligand
      deposition. The expression and protein synthesis of alpha-6 and beta-4 was
      evaluated and an increase in the synthesis of alpha-6 and beta-4 was not detected
      until 18 hr on LM and 21 hr on FN. The present results demonstrate that
      expression and transport of integrin receptors to the plasma membrane of primary
      corneal epithelial cells after adhesion is regulated by the presence of specific
      ligands.

PMID- 9196384
TI  - Quantitative characterization of high- and low-affinity binding sites for basic
      fibroblast growth factor on trabecular cells of the eye.
AB  - By radioligand binding followed by Scatchard analysis, we characterized and
      quantitated the specific binding sites for bFGF on cultured trabecular meshwork
      cells obtained from freshly enucleated porcine eyes. We detected two binding
      sites: 1.67 x 10(4) +/- 5.75 x 10(2) high-affinity receptors per cell with a Kd
      of 33.4 +/- 7.90 pM, and 1.70 x 10(4) +/- 7.57 x 10(5) low-affinity binding sites
      per cell with a Kd of 3.84 +/- 1.41 nM. At low concentrations of 125I-bFGF (<
      1.50 ng ml-1), binding was primarily determined by the high-affinity receptors
      and, at high concentrations (> 2.50 ng ml-1), binding was dependent on the low
      affinity binding sites. By phase-contrast time-lapse video micrography and
      sequential photomicrography, we demonstrated that at a concentration of 1 ng ml
      1, bFGF significantly stimulated the rate of mitosis of the trabecular meshwork
      cells in G0-phase compared with control cultures maintained in serum-free medium
      alone. Treatment with higher concentrations of bFGF did not reveal more potent
      effects on these cells. Our findings demonstrate that trabecular meshwork cells
      do possess low- and high-affinity receptors for bFGF and that bFGF induces these
      cells in vitro to re-enter the cell cycle. Because the low-affinity interactions
      of 125I-bFGF were reduced by 75% following pretreatment of the trabecular
      meshwork cells with heparinase, these sites represent cell-associated heparin
      like molecules and heparan sulfate proteoglycans, and may control the
      bioavailability of bFGF to ocular tissues. Heparinase treatment also resulted in
      a 30% reduction in high-affinity binding, which may be secondary to the decreased
      low-affinity binding. This finding agrees with the well-established scheme for
      bFGF-receptor interaction. We conclude that bFGF at the concentration present in
      aqueous humor is capable of stimulating the mitotic activity of trabecular
      meshwork cells in vitro, suggesting a possible paracrine role of aqueous humour
      bFGF in vivo. The results obtained in this study, together with our previous
      findings on bFGF mRNA expression by trabecular meshwork cells and protein
      deposition in this tissue, also indicates that trabecular cells of the eye may
      utilize bFGF by an autocrine mechanism.

PMID- 9196385
TI  - Herpes virus infection of RPE and MDCK cells: polarity of infection.
AB  - Our objective was to determine quantitatively whether herpes simplex virus
      infects preferentially the apical or basolateral surfaces of two well
      differentiated cell types, human retinal pigment epithelial cell and Madin-Darby
      canine kidney epithelial cells. Secondarily, we sought to localise the mannose 6
      phosphate/insulin-like growth factor II receptor, a putative receptor for herpes
      simplex virus, in the membrane domains of the retinal pigment epithelial cells.
      Although it has been suggested that receptors utilized by the herpesviruses are
      heterogeneously distributed on epithelial cells, no quantitative evidence of
      preferential polarized uptake of wild-type herpes simplex virus into an
      epithelial cell has yet appeared. Moreover, no evidence has appeared of the
      distribution of mannose-6-phosphate/insulin-like growth factor II receptor in
      human retinal pigment epithelial cells. We hypothesized that the preferred pole
      of uptake and infection by HSV would correlate with the distribution of the
      receptor. Understanding the preferred site of entry in these cells may shed light
      on the mechanism of pathological infection and spread of this and related
      viruses, such as cytomegalovirus, in acute retinal necrosis and herpetic
      encephalitis. The efficiency of viral infection was assayed two ways. First,
      using permeable filters on which the monolayer of polarized epithelial cells was
      grown, we compared the number of foci of infected cells that resulted from an
      apical infection with that resulting from application of virus to the underside
      of the filter from which the virus could reach the basolateral surface of the
      cells. Second, we compared the number of infected cell foci that resulted from an
      apical infection to the number formed following infection at both the apical and
      basolateral surfaces of the cells. Both surfaces were exposed to virus following
      disruption of the tight junctions between cells with a Ca2+ chelator. After the
      efficiency of infection was normalized for relative surface areas, we found that
      both cell types were equally infectable with the F strain of the virus. However,
      there was a difference in the degree of polarized uptake of virus by the two cell
      types. Virus infected the basolateral surface of the retinal cells only about 6.5
      times as effectively as it infected the apical surface of those cells, whereas
      virus infected the basolateral surface of the kidney epithelial cells about 435
      times as effectively as it infected the apical surface of the same cells. These
      data suggest that herpes simplex virus can efficiently enter either the apical or
      basolateral surface of retinal pigment epithelial cells, unlike its more
      polarized preference for the basolateral surface of the kidney epithelial cell
      type. The mannose 6-phosphate/insulin-like growth factor II receptor was present
      in human retinal pigment epithelial cells, as determined by Western blotting.
      Surface biotinylation experiments revealed the presence of the receptor in both
      the apical and basolateral membranes of the retinal epithelial cells. Our
      evidence is consistent with the hypothesis that the virus may utilize the mannose
      6-phosphate/insulin-like growth factor II receptor to facilitate entry.

PMID- 9196386
TI  - Fibronectin facilitates corneal epithelial wound healing in diabetic rats.
AB  - To determine whether the effect of fibronectin on corneal epithelial healing
      occurs in eyes affected by diabetes, the effect of fibronectin on the rates at
      which corneal epithelial wounds healed was compared in diabetic and normal rats.
      Streptozotocin was used to induce diabetes in rats. Two weeks after treatment,
      the whole corneal epithelium of diabetic and untreated rats was debrided.
      Fibronectin eye drops, at concentrations ranging from 0-01 to 1 mg ml-1, were
      given six times a day for three days, starting immediately after debridement. The
      area of the corneal epithelial wound was measured every 12 hr. Although the
      healing process was similar in normal and diabetic rats, the healing rate in
      diabetic rats was slower than that in normal controls after the 12 hr immediately
      following debridement. In both diabetic and normal rats, fibronectin eye drops
      reduced the wound area in a dose-dependent manner. The fibronectin dose of 1 mg
      ml-1 reduced the wound area significantly, compared with control eyes treated
      with phosphate-buffered saline. These results demonstrated that fibronectin
      facilitates corneal epithelial wound healing in diabetic rats.

PMID- 9196387
TI  - Retinal GFAP and bFGF expression after multiple argon laser photocoagulation
      injuries assessed by both immunoreactivity and mRNA levels.
AB  - The expression of GFAP and bFGF after retinal photocoagulation injury in the rat
      was assessed by immunocytochemistry and reverse transcriptase PCR. Beta-actin
      mRNA expression was unaltered after injury and was therefore a good control for
      the quality of the RNA samples and the PCR reaction. GFAP mRNA increased from
      undetectable levels in normal retina to relatively high levels at 24 and 48 hr
      after injury, returning to barely detectable levels at 3 and 7 days. Muller cell
      GFAP immunoreactivity was elevated by 24 hr, stronger by 48 hr and persisted for
      30-45 days. Thus, the expression of GFAP immunoreactivity after photocoagulation
      was due to new protein synthesis but the mRNA, and therefore the stimulus, was
      only present for a few days. This indicates that the GFAP protein in Muller cells
      has a long lifetime similar to that of astrocytes despite different gene control
      elements. bFGF is a possible stimulus for Muller GFAP expression because Muller
      cells have bFGF receptors. bFGF mRNA was detectable in normal, 24 and 48 hr
      retinas but decreased to undetectable levels (even after 35 cycles of PCR) at
      three days after injury and had only partly recovered by 7 days.
      Immunocytochemistry demonstrated a rapid change in localization of bFGF at the
      lesion sites early after lesion. At 2-3 days bFGF in blood vessels was markedly
      increased while at 7 days there was an increase around the photoreceptors
      flanking each lesion. These shifts in bFGF localization were too late to be a
      stimulus for the widespread upregulation of GFAP expression by Muller cells. The
      reduction in bFGF mRNA at three days was unexpected as studies of brain injury
      generally show a longer lasting elevation of bFGF expression. Therefore it is
      likely that bFGF expression is controlled by different mechanisms in the retina
      compared to the brain. However, a reduction in bFGF synthesis after
      photocoagulation is consistent with the anti-angiogenic effect of laser
      photocoagulation in diabetic retinopathy.

PMID- 9196388
TI  - Confocal light microscopy and scanning electron microscopy of the human eye lens.
AB  - The potential of confocal light microscopy (CLM) for in vivo observation of
      pathology in the anterior pole of the eye lenses was evaluated by performing an
      in vitro study of human lenses comparing this type of microscopy with scanning
      electron microscopy (SEM). In vitro CLM showed high resolution images of the
      epithelium which would enable early detection of pathology and easily allows cell
      counting and estimating cell size. Superficial lens fibres are well visualised
      and low and high frequency bands as well as vacuolar elements were easily
      detected. SEM observations fully supported the CLM observations. This study shows
      that CLM has the potential to become a useful tool for detecting lens changes,
      after suitable adaptation for clinical use.

PMID- 9196389
TI  - Oral administration of lens homogenate suppresses antibody production in mice
      injected with beta-crystallin emulsified in CFA.
AB  - Auto-antibodies (Abs) against lens antigens (Ags) are present in most patients
      with age-related cataract, and with complement they kill lens epithelial cells
      (LECs) in vitro. We studied, in an animal model, whether cytotoxic Abs against
      lens Ags can be suppressed by oral administration of the Ags. Mice were fed calf
      lens homogenate, 4 mg/mouse, every 4 days for 4-5 weeks, or bovine serum albumin
      (BSA) before and after immunisation with beta-crystallins emulsified in complete
      Freund's adjuvant (CFA). Sera from these animals were analysed for Abs to beta
      crystallins by enzyme-linked immunosorbent assay (ELISA) and protein blot
      analysis. In addition, we studied the proliferative response of T-lymphocytes to
      beta-crystallins. The titer of anti-beta-crystallin Abs in the control animals
      fed BSA gradually increased to 1.5 x 10(-6) by the 5th week after the first
      injection. In contrast, the titer of anti-beta-crystallin Abs in animals fed calf
      lens homogenate was reduced to 30-70% of the control. Feeding lens homogenate
      prior to or concomitant with beta-crystallins immunization, was more effective
      than feeding after immunization (65% suppression vs. 30% suppression,
      respectively). Also the proliferative response of T-lymphocytes to beta
      crystallins in mice fed homogenate was suppressed significantly. Thus, oral
      administration of lens homogenate is a specific and nontoxic method of
      suppressing anti-beta-crystallin Ab production in mice. We are exploring the
      therapeutic value of oral administration of lens proteins in age-related
      cataract.

PMID- 9196390
TI  - Loss of cytoskeletal proteins and lens cell opacification in the selenite
      cataract model.
AB  - This study of lens protein composition found that some cytoskeletal proteins were
      degraded during the earliest stages of cataract formation. Cataract was induced
      in 13-14 day old rats by a single subcutaneous injection of sodium selenite (19
      mumol kg-1). By 24 hr after the injection of selenite, the ratio of insoluble to
      soluble protein increased as lens opacification began. The increase in insoluble
      protein aggregates was correlated with an accelerated loss of proteins having
      molecular weights of 42, 55/57 and 235 kDa which reacted with antibodies to the
      cytoskeletal proteins actin, tubulin/vimentin and spectrin, respectively. We
      observed the loss of 49, 60 and 90 kDa proteins which were not identified. In the
      lenses of animals protected from protein aggregation and opacification by
      administration of 1.5 mmol kg-1 pantethine, the pattern of proteins in SDS-PAGE
      gels resembled the pattern for proteins from transparent lenses of normal
      untreated animals and loss of cytoskeletal proteins was prevented.

PMID- 9196391
TI  - Regulation of melanogenesis by human uveal melanocytes in vitro.
AB  - The purpose of this study was to investigate factors regulating melanogenesis in
      cultured human uveal melanocytes. The effects of various substances on the
      melanin content, tyrosinase activity and growth of cultured uveal melanocytes
      were tested. 12-O-tetradecanoyl-phorbol-13-acetate (a protein kinase C activator)
      and various cAMP-elevating agents, including isobutylmethylxanthine, cholera,
      toxin, and dibutyryl-cAMP increased melanin content per culture, tyrosinase
      activity and cell numbers of uveal melanocytes in a dose dependent manner. Basic
      fibroblast growth factor (tyrosine kinase activator) stimulated growth but did
      not affect melanin content per culture of uveal melanocytes in vitro. These
      results indicate that cAMP-elevating agents and protein kinase C activator
      stimulate melanogenesis and growth of cultured uveal melanocytes. Tyrosine kinase
      activator stimulates growth but not melanogenesis of cultured uveal melanocytes.

PMID- 9196392
TI  - Effects of UV-B radiation on a hereditary suture cataract in mice.
AB  - UV-B (290-320 um, lambda max = 305 nm) radiation and the Cat2ns (suture cataract)
      mutation in mice affect both the anterior lens epithelium and the formation of
      the suture. A low dose of UV-B radiation (2.2 Jcm-2) induces similar anterior
      subcapsular and cortical lens opacities in wild type as in heterozygous mutant
      mice. The UV-B treatment of the mutant lenses, however, leads to an increase in
      the number of epithelial cell layers in the anterior central part as compared to
      the wild type indicating a more severe form of the cataract formation in mutants.
      In addition, mutants demonstrate a predisposition for a rupture of the posterior
      lens capsule, because from 2.9 Jcm-2 and higher, this phenomenon could always be
      observed in the UV-B treated mutants, but never in the treated wild type mice.
      The protein biochemical analyses were performed by gel electrophoresis and
      isoelectric focusing of extracts of total lenses or from defined areas of the
      lens (lens slice technique). These covered the patterns of those proteins already
      synthesized before irradiation, which in irradiated lenses in no case evidenced a
      difference to the untreated control, neither in the wild type nor in the mutants.
      In contrast, by analysing specifically those proteins, which are synthesised
      after irradiation, in both treated groups a protein with a molecular mass of
      about 31 kDa becomes discernable in both treated groups. In addition, the
      cataractous lenses demonstrate a significantly enhanced overall synthesis of
      water-soluble proteins after irradiation, which might promote the rupture of the
      posterior capsule at the posterior pole. The present study offers for the first
      time the possibility to discriminate between endogeneous (genetic) effects and
      exogeneous (environmental) effects in cataractogenesis and to study their
      interactive effects. The first set of experiments demonstrated a clear
      intensification of the hereditary cataract by the UV-B treatment. The study
      supports the hypothesis that environmental stress (like UV-B radiation) enhanced
      the severity of genetically triggered eye disease.

PMID- 9196393
TI  - Mechanisms by which ascorbic acid increases ferritin levels in cultured lens
      epithelial cells.
AB  - A previous study demonstrated that ascorbic acid increased the concentration of
      the iron storage protein, ferritin. In cultured lens epithelial cells. The
      current study was designed to determine the mechanism by which ascorbic acid
      exerts this effect. Ascorbic acid increased both ferritin mRNA levels (by about
      30%) and translation of ferritin (de novo synthesis was increased up to 15-fold)
      within 6 hr. Cycloheximide completely abolished the ability of ascorbic acid to
      increase ferritin levels, whereas actinomycin D only decreased it by about 30%.
      Therefore, the ascorbic-acid induced increase in ferritin concentration is due
      mainly to an increase in ferritin synthesis at the translational levels. This is
      a novel role for ascorbic acid. Addition of iron with ascorbic acid further
      increased de novo synthesis of ferritin, but this additive effect was only noted
      at a later time point (20 hr). Factors which decrease ferritin mRNA translation,
      such as the reducing agent dithiothreitol or the iron chelator desferrioxamine,
      reduced the ascorbic acid effect on de novo ferritin synthesis. The effects of
      ascorbic acid on ferritin mRNA levels may be mediated by its oxidation product,
      H2O2, since, like ascorbic acid, H2O2 increased ferritin mRNA levels by 30%.
      However, in contrast to the ascorbic acid-induced increase in translation of
      ferritin, H2O2 substantially decreased de novo ferritin synthesis. This effect of
      H2O2 could have physiological significance in eyes where concentrations of H2O2
      in the aqueous humor are elevated. High levels of H2O2 could decrease the
      concentration of ferritin within the lens. Since ferritin sequesters iron and has
      been shown to decrease oxidative damage by limiting the availability of iron to
      catalyse free radical reactions, H2O2-induced reduction in ferritin concentration
      in the lens could have deleterious effects. The ability of ascorbic acid to
      increase ferritin concentration in lens epithelial cells could provide an
      additional protective mechanism for this antioxidant vitamin. The importance of
      ferritin to normal lens functioning is underscored by the recent finding that
      humans with a dominantly inherited abnormality in ferritin synthesis exhibit
      early bilateral cataracts.

PMID- 9196395
TI  - Age-dependent lens changes in galactose-fed dogs.
AB  - Aldose reductase initiated sugar cataract formation in 9-month old galactose-fed
      dogs has been documented to progress from an accentuation of lens sutures (1
      month after initial feeding) to the appearance of cortical vacuoles (3 months),
      cortical opacities (4-6 months) and eventually the progressive formation of a
      clear zone at the cortical equatorial regions of the cataractous lenses (> 12
      months). Here, the effect of age on the onset and degree of sugar cataract
      formation has been investigated in beagles fed a 30% galactose diet starting at
      2, 6, and 24 months of age. Cataract formation was monitored by slit lamp and
      retroillumination microscopy. Compared to 9-month old dogs, cataract formation in
      the younger dogs was more rapid and the lens changes were more severe. In the 2
      month old group of dogs, galactose-feeding resulted in a rapid formation of dense
      cataracts which began to resorb after 106 days of galactose feeding with only
      opaque nuclear remnants remaining after eight months. These changes were mirrored
      by age-dependent reductions of lenticular NADPH-dependent reductase activity.

PMID- 9196394
TI  - Properties of alpha-crystallin bound to lens membrane: probing organization at
      the membrane surface.
AB  - Alpha crystallin, one of the three major soluble proteins of the eye lens,
      appears to be a natural extrinsic protein of lens plasma membrane. Membrane
      immobilized alpha-crystallin could provide a template for the increased
      association of protein with lens membrane seen in aging and cataracts. Alpha
      crystallin binds to lens membrane through both a high-affinity saturable and low
      affinity nonsaturable process. The organization of alpha-crystallin at the
      membrane surface was proved by the examination of various chemical reactivities
      and a functional property of the membrane bound protein. The carboxyl-terminal
      domain of membrane bound alpha-crystallin appeared to be as readily cleaved by
      mild trypsinolysis as that of the soluble protein and the cleaved protein
      remained bound to the membrane. The immobilized protein was more extensively
      crosslinked by a bifunctional primary amine-reactive agent than the soluble
      protein. No evidence for crosslinking to membrane intrinsic protein was obtained.
      Like soluble alpha-crystallin, the membrane bound protein displayed chaperone
      like activity, a property dependent upon quaternary structure. These findings
      were interpreted to indicate that alpha-crystallin binds to lens membrane as an
      aggregate with only a fraction of each aggregate in direct contact with the
      membrane's hydrophobic surface. It is suggested that the nonsaturable binding
      reflects low affinity association of soluble alpha-crystallin with a layer of
      membrane-immobilised protein.

PMID- 9196396
TI  - Changes in calpain II mRNA in young rat lens during maturation and cataract
      formation.
AB  - The purpose of these experiments was to describe the expression of mRNA for
      calpain II proteolytic enzyme (EC 3.4.22.17) during normal maturation of rat lens
      and in cataract formation. Quantitative RT-PCR indicated that the concentration
      of mRNA for calpain II in whole lens was 3-24 times higher than in age-matched
      rat liver, kidney, lung and brain, and it was at least five times higher than in
      young human lens. mRNA levels for calpain II were highest in the outer regions of
      young rat lens at 5 x 10(6) copies microgram-1 total RNA. Early-stage
      experimental cataract caused increased calpain II mRNA, while mature nuclear
      cataract showed a 64% loss. In contrast, mRNA levels for GAPDH, beta-actin, and
      lens-specific structural protein beta A4 remained constant during experimental
      cataract formation. Unlike the lower and constant levels in rat liver, kidney and
      lung; calpain II mRNA levels in whole rat lens decreased with age. These data
      help explain the high enzymatic activity of calpain II in young rat lens,
      susceptibility of young rat lens to a variety of cataracts showing increased
      calcium and calpain-induced proteolysis, and low calpain enzyme activity in human
      lens. Since the up-regulation of calpain II mRNA was more dynamic than either the
      amounts of calpain II enzyme or proteolysis of crystallins in cortex, resulting
      proteolytic activity against the bulk of lens proteins seems to be regulated by
      post-translational factors, such as increased calcium. The precise role of the up
      regulation of calpain II mRNA is unknown, but we hypothesize that it may be
      associated with the initial cataractogenic response in the epithelial cells or
      peripheral cortical fibers.

PMID- 9196397
TI  - Prostaglandin effects on the contractility of bovine trabecular meshwork and
      ciliary muscle.
AB  - The ocular hypotensive activity of prostaglandins (PGs) has previously been
      demonstrated in various species including man. The underlying mechanism of action
      of prostanoids other than PGF2 alpha remains contentious. Because the trabecular
      meshwork and ciliary muscle are believed to have a role in the regulation of
      aqueous humor outflow, the aim of this study was to identify the PG-receptor
      subtypes present in these tissues using receptor-selective agonists. Contractions
      of isolated strips of bovine trabecular meshwork and ciliary muscle were recorded
      isometrically in continuously perfused tissue chambers. Contractile activity of
      PGs was determined relative to a maximally effective concentration of carbachol
      (1 microM) as a standard agonist. The following prostanoids were employed: PGF2
      alpha, 17-phenyl PGF2 alpha (FP-receptor agonists), sulprostone (EP3 > EP1
      agonist), AH13205 (EP2-agonist), 11-deoxy PGE1 (non-selective EP-agonist), and U
      46619 (TP-agonist). The thromboxane-mimetic U-46619 elicited a strong contraction
      of the trabecular meshwork with the highest concentration (1 microM) being almost
      twice as efficacious (186.6%) as the maximal carbachol concentration, whereas the
      effect on the ciliary muscle was small. The U-46619 induced trabecular meshwork
      contraction could be blocked with a potent and selective TP-receptor antagonist,
      1 microM SQ29548, indicating the involvement of TP-receptors. The other PG
      analogs studied had either no or a small but statistically significant effect.
      Thus, 17-phenyl PGF2 alpha (1 microM) weakly contracted the ciliary muscle
      (4.8%), sulprostone (1 microM) the trabecular meshwork (10.1%), 11-deoxy PGE1 (1
      microM) and AH13205 (10 microM) elicited relaxations in both tissue precontracted
      with carbachol (1 microM). The relaxant effects were more pronounced in
      trabecular meshwork (15.6% for 11-deoxy PG1 and 21.4% for AH13205) than ciliary
      muscle (6.8 and 7.4% respectively). PGF2 alpha did not elicit a significant
      response in either tissue. Our studies suggest the existence of TP- and EP2
      receptors in the bovine trabecular meshwork and potentially FP- and EP2-receptors
      in the ciliary muscle. In conclusion, thromboxane-mimetics and EP2-agonists have
      opposing activities on contractile elements in the meshwork and may modulate
      trabecular outflow in a functionally antagonistic manner. Prostanoid effects on
      ciliary muscle appear rather modest compared to parasympathomimetic drugs. It is
      conceivable that TP-agonists may substantially affect trabecular outflow.

PMID- 9196398
TI  - Retinyl palmitate in macaque retina-retinal pigment epithelium-choroid:
      distribution and correlation with age and vitamin E.
AB  - Retinyl palmitate (RP) and retinyl stearate (RS) are of central importance in the
      visual cycle because they are the major storage molecules for retinol. In some
      tissues (e.g. liver) the amount of vitamin A (mostly in the form of retinyl
      ester) is positively correlated with both the amount of alpha-tocopherol (alpha
      T) and age. Furthermore, alpha-T is a noncompetitive inhibitor of the hydrolysis
      of RP. We measured RP, RS, alpha-T and beta+gamma-tocopherol (beta+gamma-T) as
      functions of distance from the foveal center (eccentricity) in the retina-RPE
      choroid (NRC) of rhesus monkeys using high-pressure liquid chromatography. It was
      found that the central and peripheral NRC differed with respect to these
      parameters. The concentration (pmoles sq mm-1) of RP was higher in the central
      NRC than in the peripheral NRC and was at a maximum in the region of the fovea.
      Furthermore, although in the peripheral NRC. RP was well correlated with age and
      alpha-T (similar to other tissues), in the central NRC, RP per sq mm was more
      clearly related to photoreceptor density. These differences imply that the
      central NRC controls the concentration of RP within it, while the concentration
      of RP in the peripheral NRC is determined by its environment (e.g. nutrients
      available from blood) and the age of the individual.

PMID- 9196399
TI  - Regional scleral changes in form-deprivation myopia in chicks.
AB  - Similar neurochemical events appear to be involved in the development of myopia
      in chicks and mammals. The rapid post-hatching development of the chick is ideal
      for studying experimental myopia. In this investigation, one eye of 2-day-old
      chicks was deprived of form vision for 2 weeks and then compared to the fellow,
      non-deprived eye by immunohistochemistry and light and electron microscopy. All
      deprived eyes showed a high refractive error and ocular enlargement. In deprived
      eyes, the posterior cartilaginous sclera was thicker and the fibrous sclera of
      the same section was thinner than the control. Scleral morphological changes were
      restricted to a central button 6-7 mm in diameter (the posterior pole) within the
      posterior hemisphere, further divided into posterotemporal and posteronasal
      parts. The most enlarged, posterior cartilaginous structure of deprived sclera
      could be divided into an inner and an outer zone. The inner zone had many
      unevenly-arranged chondrocytes, each having a well-developed granular endoplasmic
      reticulum and Golgi complex and a very irregular cell surface. Numerous S-phase
      cells and isogenous groups were detected in the outer zone. Hypertrophic
      chondrocytes were often observed in the innermost region of the outer zone and
      the outermost region of the inner zone. The boundary between the outer fibrous
      sclera and the cartilaginous sclera was irregular and obscured in myopic eyes.
      Spindle-shaped chondrocytes were seen to be in contact with each other. Thick
      collagen fibrils, usually seen only in the outer fibrous sclera, were present
      among the chondrocytes. Results of this morphological study suggest an increased
      proliferation of chondrocytes and active synthesis of extracellular matrix in
      visually deprived eyes. The elongation of the ocular axis that accompanies myopia
      is caused primarily by an active remodeling and differentiation in a restricted
      section of the posterior scleral cartilage. These facts indicate the posterior
      scleral cartilage may be more immature than cartilage in anterior and lateral
      segments.

PMID- 9196400
TI  - The contribution of GSH peroxidase-1, catalase and GSH to the degradation of H2O2
      by the mouse lens.
AB  - Utilizing cultured lenses from normal and homozygous glutathione peroxidase
      (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2
      chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the
      ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and
      80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2
      degradation. The Cat contribution was concentration dependent being about 30% at
      300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured
      as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2
      degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM
      and 80 microM, respectively. However, based on evaluation of the ability of GSH
      to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM
      and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is,
      therefore, concluded that lens GSH must be involved in other reactions either
      directly or indirectly related to H2O2 degradation.

PMID- 9196402
TI  - Extralenticular expression of the alpha A-crystallin promoter/gamma interferon
      transgene.

PMID- 9196401
TI  - A carboxy-terminal truncation of 99 amino acids resulting from a novel mutation
      (Arg555-->stop) in the CHM gene leads to choroideremia.

PMID- 9196403
TI  - Atrial fibrillation begets trouble.

PMID- 9196404
TI  - Hypercoagulability and haemodynamic abnormalities in atrial fibrillation.

PMID- 9196405
TI  - Assessing atherosclerotic plaque morphology: comparison of optical coherence
      tomography and high frequency intravascular ultrasound.
AB  - BACKGROUND: OCT can image plaque microstructure at a level of resolution not
      previously demonstrated with other imaging techniques because it uses infrared
      light rather than acoustic waves. OBJECTIVES: To compare optical coherence
      tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro
      atherosclerotic plaques. METHODS: Segments of abdominal aorta were obtained
      immediately before postmortem examination. Images of 20 sites from five patients
      were acquired with OCT (operating at an optical wavelength of 1300 nm which was
      delivered to the sample through an optical fibre) and a 30 MHz ultrasonic
      transducer. After imaging, the microstructure of the tissue was assessed by
      routine histological processing. RESULTS: OCT yielded superior structural
      information in all plaques examined. The mean (SEM) axial resolution of OCT and
      IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point
      spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB
      compared with 43 dB for IVUS imaging. CONCLUSIONS: OCT represents a promising new
      technology for intracoronary imaging because of its high resolution, broad
      dynamic range, and ability to be delivered through intravascular catheters.

PMID- 9196406
TI  - Acquired aortic regurgitation following occlusion of the persistent arterial
      duct: an echocardiographic assessment.
AB  - OBJECTIVE: To document the development of aortic regurgitation following
      occlusion of a patent arterial duct. DESIGN: Case series involving nine children
      referred for surgical ligation of an isolated patent arterial duct. SETTING:
      Academic referral centre. METHODS: A preoperative transthoracic and
      transoesophageal echocardiogram was performed in theatre to look for aortic
      regurgitation. Thereafter, aortic flow was monitored throughout the operation by
      colour flow mapping with the transoesophageal probe in situ. Onset of aortic
      regurgitation was documented. An immediate postoperative transthoracic
      echocardiogram was performed on all patients and then daily until discharge on
      day 5. A follow up clinical and echocardiographic assessment was performed six
      weeks postoperatively. RESULTS: With ligation of the patient arterial duct,
      transoesophageal echocardiography showed immediate regurgitation in seven of the
      nine patients, seen as a small central jet on colour flow mapping. Six of the
      seven patients continued to have aortic regurgitation on transthoracic
      echocardiography before leaving theatre. In none was aortic regurgitation audible
      clinically. At discharge, five patients still had evidence of aortic
      regurgitation; of four seen at follow up six weeks later, only one had residual
      regurgitation. CONCLUSIONS: Ligation of the patient arterial duct results in the
      acute termination of the "run off" in a volume overloaded situation. This,
      together with a rise in the peripheral vascular resistance and the persistence of
      increased proximal vascular capacitance, is considered to be the underlying
      aetiology of the acquired aortic regurgitation.

PMID- 9196407
TI  - Christiaan Neethling Barnard (1922-).

PMID- 9196409
TI  - Reproducibility of the signal averaged P wave: time and frequency domain
      analysis.
AB  - OBJECTIVE: To assess the reproducibility of time and frequency domain variables
      derived from the signal averaged P wave. DESIGN: Longitudinal within patient
      study. SETTING: Regional cardiothoracic centre. PATIENTS: 20 patients (10 with
      documented paroxysmal atrial fibrillation and 10 normal controls) were studied on
      three occasions to assess the reproducibility of repeated signal averaged P wave
      recordings. Digital P wave recordings were made on a further 10 patients on a
      single occasion and the recordings signal averaged twice in order to assess the
      reproducibility of the averaging system itself in the absence of biological
      variation. MAIN OUTCOME MEASURES: P wave duration, spatial velocity, and energies
      contained in frequency bands from 20, 30, and 60-150 Hz of the P wave spectrum
      were measured after P wave specific signal averaging. Coefficients of
      reproducibility were calculated for paired signal averaged P waves derived by
      signal averaging the same digital recordings on two separate occasions, for
      recordings performed in the same patients immediately after each other ("back to
      back") and those performed one week apart. RESULTS: System reproducibility when
      the same digital P wave recordings were signal averaged on two separate occasions
      was high (< 11% for all variables). For P wave duration the coefficient of
      reproducibility was 11.4% for back to back recordings and 13.1% for those one
      week apart. The reproducibility of spatial velocity and P wave energy was low.
      Variation in P wave morphology was noted when successive P waves from the same
      subject were examined. If recordings with the same P wave morphology were
      analysed the reproducibility of spatial velocity and P wave energy improved but
      remained significantly poorer than that for P wave duration. CONCLUSIONS: P wave
      duration is reproducible within subjects in the short and medium term. Frequency
      domain and spatial velocity analysis are poorly reproducible, due more to
      spontaneous variation in P wave morphology than to instability of the signal
      averaging process. This may limit the utility of signal averaged P wave variables
      other than duration for the prediction of atrial arrhythmia.

PMID- 9196408
TI  - Haemostatic and haemodynamic abnormalities associated with left atrial thrombosis
      in non-rheumatic atrial fibrillation.
AB  - OBJECTIVE: To evaluate the role of haemostatic and haemodynamic variables in left
      atrial thrombosis in non-rheumatic atrial fibrillation. DESIGN: Case-control
      study. SUBJECTS: One hundred and nine patients with non-rheumatic atrial
      fibrillation. INTERVENTIONS: Peak blood velocity measured at three sites in the
      left atrium. Venous blood sampled for coagulant proteins and markers of
      haemostatic activation. MAIN OUTCOME MEASURES: Presence of left atrial thrombus
      and spontaneous echo contrast at transoesophageal echocardiography. RESULTS: Left
      atrial thrombus was identified in 19 patients (18%), 16 of whom had spontaneous
      echo contrast. Patients with thrombus had reduced peak left atrial appendage
      velocity compared with those without (0.17 v 0.26 m/s; P < 0.001), but no
      significant reductions in peak mid-left atrial or mitral valve outflow velocity.
      Patients with thrombus had increased plasma markers of platelet activation-beta
      thromboglobulin (56.8 v 30.4 IU/ml; P < 0.001) and platelet factor 4 (6.1 v 3.5
      IU/ml; P < 0.01)-and of thrombogenesis: thrombin-antithrombin complexes (5.59 v
      3.06 micrograms/ml; P < 0.001) and D-dimers (479 v 298 ng/ml; P < 0.01). von
      Willebrand factor was also increased (1.81 v 1.52 IU/ml; P < 0.05). A multiple
      logistic regression model identified left atrial appendage velocity (P = 0.001),
      beta thromboglobulin (P = 0.002), and von Willebrand factor (P = 0.04) as the
      independent associates of left atrial thrombosis, ahead of the presence of
      spontaneous echo contrast. CONCLUSIONS: Haemostatic and haemodynamic
      abnormalities are associated with left atrial thrombus in non-rheumatic atrial
      fibrillation, and may help stratify thromboembolic risk.

PMID- 9196410
TI  - Signal averaged P wave compared with standard electrocardiography or
      echocardiography for prediction of atrial fibrillation after coronary bypass
      grafting.
AB  - OBJECTIVE: To define the clinical value of the signal averaged P wave (SAPW) and
      to compare it with the standard electrocardiogram (ECG), echocardiogram, and
      clinical assessment for the prediction of atrial fibrillation after coronary
      bypass grafting (CABG). DESIGN: Prospective validation cohort study. SETTING:
      Regional cardiothoracic centre. PATIENTS: 201 unselected patients undergoing
      first elective CABG were recruited over six months. Patients requiring
      concomitant valve surgery were excluded. MAIN OUTCOME MEASURES: Age, sex,
      cardiothoracic ratio, and cardioactive drugs were noted. P wave specific SAPW
      recordings, ECG, and M mode echocardiograms from which left atrial diameter was
      measured were performed within 24 hours of surgery. Filtered P wave duration
      (SAPWD), spatial velocity, and energy were calculated from the SAPW. From the
      ECG, lead II P wave duration, P terminal force in lead V1, total P wave duration,
      and isoelectric interval were measured. Patients had Holter monitoring for 48
      hours postoperatively and daily ECGs until discharge. RESULTS: Two patients died
      (1%) and 10 were unsuitable for analysis (5%). Of the remaining 189, 51 (27%) had
      atrial fibrillation (AF) lasting > 1 hour at a mean of 2 (0.5 to 7) days after
      CABG. Of the variables examined, only SAPWD (AF group 148 (SD 12), v 142 (14) ms,
      P = 0.008) and male sex (AF group 96%, v 78%, P < 0.01) were significantly
      different. A prospectively defined SAPWD of > 141 ms predicted atrial
      fibrillation with positive and negative predictive accuracies of 34% and 83%.
      Logistic regression analysis identified both male sex and SAPWD as significant
      independent predictors of postoperative atrial fibrillation. CONCLUSIONS: Signal
      averaged P wave duration was a better predictor of atrial fibrillation after
      coronary bypass grafting than standard electrocardiographic or echocardiographic
      criteria. The predictive value of this test is such that it is likely to be
      useful in the design of prospective trials of prophylactic antiarrhythmic
      treatment but is of limited use using current techniques in the clinical
      management of individual patients.

PMID- 9196411
TI  - Association of ventricular arrhythmias with left ventricular remodelling after
      myocardial infarction.
AB  - OBJECTIVE: To assess the relation between ventricular arrhythmias after
      myocardial infarction and left ventricular remodelling. DESIGN: Prospective study
      with consecutive patients. METHODS: 97 patients with acute myocardial infarction
      underwent serial echocardiographic examinations (days 1, 2, 3, and 7, and after 3
      weeks) to determine end diastolic volume, end systolic volume, and ejection
      fraction; volumes were normalised for body surface area and expressed as indices.
      Holter monitoring was performed on the day of the final echocardiogram. Coronary
      angiography was performed in 88 patients before hospital discharge. RESULTS:
      Complex ventricular arrhythmias (defined as Lown class 3-5) were found in 16 of
      97 patients. In logistic regression models, variables predictive of complex
      ventricular arrhythmias were end systolic volume index on admission (b = 0.054, P
      = 0.015) and end diastolic volume index after three weeks (b = 0.034, P = 0.012).
      Complex arrhythmias were also related to the increase of end diastolic and end
      systolic volume indices throughout the study (F = 5.62, P = 0.046, and F = 6.42,
      P = 0.017, respectively by MANOVA). A two stage linear regression model of
      ventricular volume versus time from infarct showed that both intercept (initial
      volume) and slope (rate of increase) were higher for patients with complex
      arrhythmias in both diastole and systole (P < 0.001 for all). CONCLUSIONS:
      Complex ventricular arrhythmias after myocardial infarction are related to the
      increase of left ventricular volume rather than to depressed ejection fraction.
      Complex arrhythmias may be an aetiological factor linking left ventricular
      remodelling with higher mortality, but larger follow up studies of patients with
      progressive left ventricular dilatation after myocardial infarction are necessary
      to answer these questions.

PMID- 9196412
TI  - Left atrial appendage function during DDD and VVI pacing.
AB  - OBJECTIVE: To examine, using transoesophageal echocardiography, the possible
      disturbances of left atrial appendage function during VVI and DDD pacing in
      patients with a normal atrium paced with a dual chamber system. DESIGN:
      Randomised controlled trial. SETTING: Tertiary care centre. PATIENTS: 22 patients
      (mean age 68 (SD 6) years) who had been paced with dual chamber pacemakers for at
      least six months. Exclusion criteria were valvar disease, cardiomyopathy,
      hypertension, and diabetes mellitus. INTERVENTIONS: All patients underwent a
      transoesophageal echocardiographic evaluation of left atrial appendage function
      under DDD and VVI modes in random order. Measurements were made after at least
      two months' pacing in each mode. MAIN OUTCOME MEASURES: Echocardiographic indices
      of left atrial appendage flow under both pacing modes. RESULTS: All 22 patients
      had higher emptying and filling flow velocities under DDD than under VVI mode.
      The filling and emptying flow velocity integrals were also significantly higher
      under DDD mode (P < 0.001, P = 0.019). CONCLUSIONS: Left atrial appendage
      function, as reflected in indices of emptying and filling assessed by
      transoesophageal echocardiography, is significantly different with DDD than with
      VVI pacing. This may explain the higher incidence of thromboembolic episodes in
      patients paced under VVI mode.

PMID- 9196413
TI  - Does a waiting time for elective coronary angioplasty affect the primary success
      rate?
AB  - OBJECTIVE: To evaluate the effect of the waiting time for elective percutaneous
      transluminal coronary angioplasty (PTCA) on the primary success rate. SETTING:
      University hospital in The Netherlands. PATIENTS: A cohort of 817 consecutive
      patients awaiting elective PTCA. Scheduled PTCA was performed in all 817
      patients, involving 1237 coronary lesions. MAIN OUTCOME MEASURES: The relation
      between procedural success and the duration of the waiting time was evaluated.
      Major cardiac events, that is, death and myocardial infarction while awaiting
      PTCA, were documented. Alterations in lesion characteristics during the waiting
      time were assessed in unsuccessful procedures. RESULTS: Elective PTCA was
      performed within one to six weeks after acceptance in 388 patients (587 lesions;
      47.5%), between six and 12 weeks in 203 patients (308 lesions; 25%), and after
      more than 12 weeks in 226 patients (342 lesions; 27.5%). The procedural success
      rates in the defined time intervals were 97%, 99%, and 97% in ACC/AHA type A
      lesions, 93%, 87% and 90% in type B lesions, and 63%, 55% and 38% in type C
      lesions respectively; 96% of type C lesions were total coronary occlusions. There
      was a significant decrease in primary success rate in type C lesions after a
      waiting time beyond 12 weeks. A reasonable explanation for an unsuccessful
      angioplasty related to alterations in lesion characteristics during the waiting
      time was documented in only four of 115 procedures. CONCLUSIONS: The primary
      success in type A and B lesions is unaffected by the duration of a waiting period
      for elective PTCA. A waiting time of more than 12 weeks is associated with a
      lower success rate in patients with total coronary occlusions.

PMID- 9196414
TI  - Predictors of hospital readmission two years after coronary artery bypass
      grafting.
AB  - OBJECTIVE: To determine the clinical factors before, and in association with,
      coronary artery bypass grafting (CABG) that increase the risk of readmission to
      hospital in the first two years after surgery. PATIENTS: All patients in western
      Sweden who had CABG without simultaneous valve surgery between 1 June 1988 and 1
      June 1991. METHODS: All patients who were readmitted to hospital were evaluated
      by postal inquiry and hospital records. RESULTS: A total of 2121 patients were
      operated on, of whom 2037 were discharged from hospital. Information regarding
      readmission was missing in four patients, leaving 2033 patients; 44% were
      readmitted to hospital. The most common reasons for readmission were angina
      pectoris and congestive heart failure. There were 12 independent significant
      predictors for readmission: clinical history (a previous history of either
      congestive heart failure or myocardial infarction, or CABG); acute operation;
      postoperative complications (time in intensive care unit greater than two days,
      neurological complications); clinical findings four to seven days after the
      operation (arrhythmia, systolic murmur equivalent to mitral regurgitation);
      medication four to seven days after the operation (antidiabetics, diuretics for
      heart failure, other antiarrhythmics (other than beta blockers, calcium
      antagonists, and digitalis), and lack of treatment with aspirin). CONCLUSION: 44%
      of patients were readmitted to hospital two years after CABG. The most common
      reasons for readmission were angina pectoris and congestive heart failure. Four
      clinical markers predicted readmission: clinical history; acute operation status;
      postoperative complications; and clinical findings and medication four to seven
      days after operation.

PMID- 9196415
TI  - Factors affecting the therapeutic choice in patients with multivessel coronary
      artery disease. The Studio Lombardo Angiografia Multivasali (SLAM) Study Group.
AB  - OBJECTIVE: To assess how clinical and angiographic findings are related to the
      decision to carry out coronary angioplasty (PTCA) or coronary bypass grafting in
      patients with multivessel coronary artery disease. DESIGN: Prospective survey
      carried out in 14 centres in the Lombardia region of Italy. PATIENTS: 1468
      consecutive patients under going coronary arteriography for known or suspected
      ischaemic heart disease between May and October 1994, who were found to have
      multivessel coronary artery disease. MAIN OUTCOME MEASURES: Multivariate analysis
      was undertaken using stepwise logistic regression to identify the clinical and
      angiographic variables correlated with revascularisation (v medical treatment) in
      all of patients, and with surgery (v angioplasty) in the subset of revascularised
      patients. RESULTS: In all patients the clinical decision after coronary
      arteriography was made by physicians of each participating centre on the basis of
      their experience and clinical judgment: 53% of patients had bypass surgery, 28%
      had PTCA, and 19% continued medical treatment. The choice of a revascularisation
      procedure was directly related to a clinical diagnosis of unstable angina (P < <
      0.001), the presence of left anterior descending artery disease (P < < 0.001),
      and to an ejection fraction > or = 40% (P < < 0.001), and inversely related to
      history of previous coronary bypass surgery (P < < 0.001). In revascularised
      patients, bypass surgery was the preferred treatment in patients with left
      anterior descending artery disease (P < < 0.001), three-vessel disease (P < <
      0.001), and in those with at least one occluded vessel (P = 0.008). The choice of
      PTCA was significantly related to history of previous PTCA (P < < 0.001) or
      coronary bypass surgery (P < < 0.001), to a clinical diagnosis of non-Q wave
      myocardial infarction (P = 0.002), and to the possibility of implanting an
      intracoronary stent (P = 0.01). CONCLUSIONS: Bypass surgery is still the most
      widely used treatment for patients with multivessel coronary artery disease. This
      analysis provides a basis for comparison with future developments in the
      treatment of such patients. Further advancements in PTCA technology are needed to
      tilt the balance in favour of this less invasive procedure.

PMID- 9196417
TI  - Importance of right ventricular outflow tract angiography in distinguishing
      critical pulmonary stenosis from pulmonary atresia.
AB  - OBJECTIVE: To investigate the spectrum of pulmonary atresia and critical
      pulmonary stenosis using right ventricular outflow tract angiography and explore
      its implications for catheter interventional treatment. DESIGN: Prospective
      clinical study. SETTING: Two paediatric cardiology centres. SUBJECTS: 11 neonates
      or infants (aged 1 day to 8 months; weighing 2.3 to 7.8 kg) with pulmonary
      atresia or where the differentiation of pulmonary atresia from critical pulmonary
      stenosis was unclear on either echocardiography or angiography. METHODS: Right
      ventricular outflow tract angiography was performed on all patients to
      distinguish pulmonary atresia from critical pulmonary stenosis before opening the
      right ventricular outflow tract. RESULTS: Right ventricular outflow tract
      angiography showed that three of seven patients diagnosed as pulmonary atresia by
      echocardiography had pin hole jets across the pulmonary valve; another had a
      probe patent valve that appeared imperforate on both echocardiography and right
      ventricular outflow tract angiography. Three of the four patients diagnosed by
      echocardiography as critical pulmonary stenosis were found on right ventricular
      outflow tract angiography to have pulmonary atresia. The remaining patient had
      such a tiny orifice that a second orifice had to be created with a radiofrequency
      catheter. The right ventricular outflow tract was opened successfully in 10 of
      the 11 patients, six of whom required application of radiofrequency energy. The
      right ventricular to aortic systolic pressure ratio fell from 1.4 (0.9 to 1.9) to
      0.6 (0.2 to 1.1) (P < 0.05). All 11 patients were alive and well with
      transcutaneous oxygen saturations ranging from 84% to 95% at a median follow up
      duration of nine months. CONCLUSIONS: Critical pulmonary stenosis and pulmonary
      atresia cannot always be accurately distinguished by echocardiography. Right
      ventricular outflow tract angiography helps to distinguish the two groups. In
      most cases the right ventricular outflow tract can be opened without mortality
      and with short to medium term survival.

PMID- 9196416
TI  - Role of leucocytes in free radical production during myocardial
      revascularisation.
AB  - OBJECTIVE: To evaluate the role of leucocytes in free radical production in
      patients with depressed or normal ejection fraction undergoing coronary bypass.
      DESIGN: Two randomised control trials. SETTING: Tertiary care centre. PATIENTS
      AND INTERVENTIONS: In the first study, 22 patients with ejection fractions of <
      or = 40% received blood cardioplegic reperfusion with (n = 11) or without (n =
      11) leucocyte depletion. In the second study, 22 patients with ejection fractions
      > or = 45% received either leucocyte depleted (n = 11) or blood cardioplegia (n =
      11). MAIN OUTCOME MEASURES: Glutathione, hypoxanthine, and lipid peroxidation
      products were measured in coronary sinus blood and plasma before aortic cross
      clamping and at 0, 15, and 30 minutes after unclamping. Haemodynamic variables
      and creatine kinase MB isoenzymes were monitored on the first postoperative day.
      Comparison between treatments was performed on difference (delta) between
      measurements at time 0 and at baseline, and on slopes obtained by fitting
      measurements after unclamping with a linear regression model. RESULTS: At
      unclamping no difference in delta for plasma glutathione redox ratio
      (oxidised/total glutathione, %) was observed between treated and control groups
      with low ejection fraction (delta = 16 (SD 8.39) and 24 (7.0) redox ratio %,
      respectively). Baseline value recovery rate (redox ratio %/min) was significantly
      faster in treated v control patients (slope -0.912 (0.380) v -0.158 (0.200), P <
      0.005, respectively). Cardiac index showed a trend to greater improvement in the
      treated group (slope 0.04 (0.03) v 0.003 (0.002) 1/min/m2/h, P < 0.02, treated v
      controls, respectively). In patients with normal ejection fraction, leucocyte
      depletion did not result in significant improvement v controls. CONCLUSIONS:
      Leucocyte depletion seems to provide benefit only in patients with left
      ventricular dysfunction.

PMID- 9196418
TI  - Cardiac manifestations of acute carbamate and organophosphate poisoning.
AB  - OBJECTIVE: To study the frequency, extent, and pathogenesis of the cardiac
      complications accompanying organophosphate and carbamate poisoning. DESIGN:
      Retrospective study. SETTING: A medical intensive care unit (MICU) of a general
      hospital. SUBJECTS: 46 adult patients admitted over a five year period with a
      diagnosis of organophosphate or carbamate poisoning. RESULTS: Cardiac
      complications developed in 31 patients (67%). These were: non-cardiogenic
      pulmonary oedema, 20 (43%); cardiac arrhythmias, 11 (24%); electrocardiographic
      abnormalities including prolonged Q-Tc interval, 31 (67%); ST-T changes, 19
      (41%); and conduction defects, 4 (9%). Sinus tachycardia occurred in 16 patients
      (35%) and sinus bradycardia in 13 (28%). Hypertension developed in 10 patients
      (22%) and hypotension in eight (17%). Eight patients (17%) needed respiratory
      support because of respiratory depression. Although more than two thirds of the
      patients (67%) had a prolonged Q-Tc interval, none had polymorphic ventricular
      tachycardia of the torsade de pointes type. Two patients died from ventricular
      fibrillation, an in hospital mortality of 4%. CONCLUSIONS: Cardiac complications
      often accompany poisoning with these compounds, particularly during the first few
      hours. Hypoxaemia, acidosis, and electrolyte derangements are major predisposing
      factors. Intensive supportive treatment in intensive or coronary care facilities
      with administration of atropine in adequate doses early in the course of the
      illness will reduce the mortality.

PMID- 9196421
TI  - Early implantation of multiple spring coils for severe haemolysis after
      incomplete transcatheter occlusion of persistent arterial duct.
AB  - An 18 month old girl with an angiographically measured ductus of 4.5 mm underwent
      transcatheter occlusion of the persistent arterial duct with a 17 mm Rashkind
      umbrella and an occluding spring coil. Severe intravascular haemolysis developed
      20 hours later. Significant residual ductal leakage was noted and the residual
      duct measured 6 mm. Previous underestimation might have been related to ductal
      spasm as a catheter was placed across the duct before angiography. The haemolysis
      was abolished within 48 hours by a previously unreported approach of antegrade
      transcatheter closure of the residual duct by multiple spring coils.

PMID- 9196420
TI  - Culture-negative endocarditis: contribution of bartonella infections.
AB  - Two cases of bartonella endocarditis are described: one in a 55 year old homeless
      alcoholic man, caused by Bartonella quintana; the other in a 41 year old male
      with a history of exposure to cat fleas, caused by B henselae. Serological
      testing and polymerase chain reaction of the excised valves were used to identify
      the organisms. False positive serology for chlamydia was detected in one case.

PMID- 9196422
TI  - Transcatheter umbrella closure of aorto-pulmonary window.
AB  - Aorto-pulmonary window (aorto-pulmonary septal defect) is an uncommon congenital
      cardiac malformation which is repaired using cardiopulmonary bypass. A case is
      described of an infant with a small aorto-pulmonary window which was closed by
      transcatheter insertion of a double umbrella device. Complete occlusion of the
      defect was achieved without complications. Transcatheter umbrella closure of a
      small aorto-pulmonary window is feasible in infancy and the technique is likely
      to be applicable in a few cases.

PMID- 9196419
TI  - Reduction of oxidative stress does not affect recovery of myocardial function:
      warm continuous versus cold intermittent blood cardioplegia.
AB  - OBJECTIVE: To compare oxidative stress after cardiac surgery in patients treated
      with two different methods of myocardial protection: warm continuous versus cold
      intermittent blood cardioplegia. To correlate oxidative stress with postoperative
      myocardial dysfunction. DESIGN: Prospective, randomised, double blind, trial.
      SETTING: Institutional centre of cardiovascular surgery. PATIENTS: 20 patients
      were selected for coronary artery bypass surgery (CABG) on the following basis:
      stable angina, ejection fraction > 50%, double or triple vessel disease, no
      previous CABG or associated disease. Patients were randomised to two groups of 10
      patients each. INTERVENTIONS: Patients underwent CABG with one of two different
      methods of myocardial protection and cardiopulmonary bypass. CBC group:
      intermittent cold blood antegrade-retrograde cardioplegia with moderate
      hypothermic cardiopulmonary bypass; WBC group: continuous warm blood antegrade
      retrograde cardioplegia with mild hypothermic cardiopulmonary bypass. MAIN
      OUTCOME MEASURE: The index of oxidative stress used was the alteration of whole
      blood and plasma glutathione redox status. Samples were collected from the
      coronary sinus and peripheral vein before anaesthesia (T1), before aortic
      unclamping (T2), 15 minutes (T3), and 30 minutes (T4) after unclamping.
      Haemodynamic parameters were measured with thermodilution techniques. RESULTS:
      Oxidised glutathione and glutathione-cysteine mixed disulphide significantly
      increased in the coronary sinus plasma in the CBC group, and the overall redox
      balance of glutathione was decreased (P < 0.01) at T2-T4 versus T1, and compared
      with the WBC group. Comparable results were obtained for coronary sinus blood.
      There was no correlation between postoperative haemodynamic measurements and
      oxidative stress markers. CONCLUSIONS: Oxidative stress was significant in
      patients undergoing CABG using cold blood cardioplegia, while the warm technique
      minimised the effects of ischaemia. However, oxidative stress was not correlated
      with myocardial dysfunction following CABG.

PMID- 9196423
TI  - Hypertrophic cardiomyopathy with apical aneurysm: a case of catheter and surgical
      therapy of sustained monomorphic ventricular tachycardia.
AB  - The case is presented of a patient with hypertrophic cardiomyopathy,
      midventricular obstruction, apical aneurysm, and very frequent episodes of
      sustained monomorphic ventricular tachycardia (VT) unresponsive to common
      antiarrhythmic drugs. Left ventricular catheter mapping during sinus rhythm
      suggested the presence of an extensively scarred apical region; early
      fractionated ECGs were recorded at the neck of the aneurysm during monomorphic
      VT, suggesting a possible role of this region as VT substrate. Radiofrequency
      delivery at these sites stopped the VT and it was no longer inducible; however,
      it spontaneously recurred the following day. An apical aneurysmectomy, guided by
      the results of catheter mapping, was performed and was successful in preventing
      arrhythmic recurrences during 12 months' follow up.

PMID- 9196424
TI  - Electrical injury on removal of implantable defibrillator after death.

PMID- 9196425
TI  - Reversible high rate atrial fibrillation dilated cardiomyopathy.

PMID- 9196426
TI  - K+ channel opening: a new drug principle in cardiovascular medicine.

PMID- 9196427
TI  - Prophylactic replacement of Bjork-Shiley convexo-concave heart valves: an easy-to
      use tool to aid decision-making in individual patients.

PMID- 9196428
TI  - Epstein-Barr virus in Hodgkin's disease: more than just an innocent bystander.
AB  - Several lines of evidence suggest that the Epstein-Barr virus (EBV) is an
      important factor in the pathogenesis of Hodgkin's disease (HD). This Editorial
      focuses on two pathogenic mechanisms probably influenced by the presence of EBV
      in the Hodgkin and Reed-Sternberg (H-RS) cells: resistance of the H-RS cells to
      apoptosis; and escape of H-RS cells from a cytotoxic T lymphocyte (CTL) mediated
      immune response. In addition, data are summarized implicating the latent membrane
      protein 1 (LMP1) as the most likely EBV-encoded protein responsible for this
      putative EBV-mediated pathogenic effect. It is known that, using conventional
      therapy regimens, the presence of EBV bears little influence on clinical
      presentation and treatment outcome of HD. However, the differences in regulation
      of both apoptosis and immune escape mechanisms between EBV+ and EBV- cases may be
      important determinants of the success of immunotherapy to treat Hodgkin's
      disease. Thus, clarification of these mechanisms will be essential to the
      development of successful immunotherapeutic strategies in Hodgkin's disease.

PMID- 9196429
TI  - Advances in the understanding of the molecular pathology of connective tissue
      neoplasms.
AB  - Although primary malignant neoplasms of the connective tissues are uncommon, they
      have been subjected to intense study by modern molecular and other analytical
      techniques. Aberrations of genes and their products are providing insight into
      aetiopathogenesis and indicating improved methods of histopathological diagnosis
      and patient management.

PMID- 9196430
TI  - Interphase cytogenetics and pathology: a tool for diagnosis and research.
AB  - Karyotypic analysis by direct demonstration of DNA sequences in interphase nuclei
      has been termed interphase cytogenetics and can be applied to a wide variety of
      cellular material, including paraffin-embedded tissue, allowing detection of both
      numerical and structural chromosome aberrations. The principal established method
      in the fluorescence in situ hybridization (FISH) technique, but more recently
      primed in situ labelling (PRINS) has been employed, as illustrated in an
      accompanying paper in this issue of the Journal. Where there are defining
      cytogenetic abnormalities, as is the case for the detection of fetal numerical
      chromosome abnormalities and in some paediatric and soft tissue tumours, this
      approach has clear diagnostic applicability. In other circumstances, such as the
      investigation of most solid tumours, this technique is largely of research
      interest but, particularly with application to paraffin sections, in providing
      valuable information on the morphological distribution of molecular changes in
      both invasive and 'pre-invasive' lesions. Continued technical refinement and
      research application of this methodology will lead not only to greater clinical
      applicability but also to improved understanding of the pathobiology of tumours.

PMID- 9196431
TI  - bcl-2 expression in pleural and extrapleural solitary fibrous tumours.
AB  - This study evaluated the immunoreactivity for bcl-2, a molecule involved in the
      control of programmed cell death, in cases of pleural (14) and extrapleural (2)
      solitary fibrous tumour (SFT), malignant mesotheliomas of different histological
      types, and a variety of extrapleural CD34-positive and CD34-negative spindle-cell
      tumours. In all SFTs, strong and diffuse immunostaining was demonstrated with
      anti-bel-2 antibody, sharply contrasting with the complete lack of staining
      observed in all mesotheliomas. The specificity of immunodetection of bcl-2 in SFT
      was confirmed by immunoblot analysis, showing a band consistent with the bcl-2
      protein. At extrapleural locations, strong bcl-2 immunoreactivity was observed in
      Schwannoma (2/3 cases), synovial sarcoma (4/4 cases), and all cases of CD34
      positive gastrointestinal stromal tumour (GIST; 10/10 cases). Most sarcomas were
      bcl-2-negative. Lack of bcl-2 expression was demonstrated in tumours which can
      pose problems in the differential diagnosis of SFT and can exhibit
      haemangiopericytoma-like features, including haemangiopericytoma (3 cases),
      dermatofibrosarcoma protuberans (16 cases), and deep-seated fibrous histiocytoma
      (3 cases). The constitutive expression of bcl-2 in SFT widens the spectrum of
      available markers for these tumours, providing a useful adjunct to their
      differential diagnosis in difficult cases at pleural and extrapleural sites, and
      contributing to the understanding of their histogenesis and molecular
      pathogenesis.

PMID- 9196432
TI  - Rapid detection of karyotype changes in interphase bone marrow cells by
      oligonucleotide primed in situ hybridization (PRINS).
AB  - Fluorescence in situ hybridization (FISH) using DNA probes of several hundred or
      thousand base pairs in length enables the visualization of chromosomal
      aberrations in interphase nuclei. A new method for in situ labelling of
      chromosomes is the oligonucleotide primed in situ labelling (PRINS) technique. So
      far, this has mainly been used to demonstrate subtle changes in metaphase
      spreads. The aim of the present study was to investigate the suitability of PRINS
      for detecting chromosome gains or losses in interphase nuclei. This technique was
      compared with FISH analysis by examining the bone marrow cells of ten patients in
      whom the karyotypes were known from conventional chromosome banding.
      Corresponding results by both PRINS and FISH were obtained for chromosomes 1, 3,
      7, 8, and Y in five patients with normal chromosome patterns, as well as in five
      patients with clonal karyotype changes, e.g., monosomy 7, trisomy 8, or loss of
      the Y chromosome. Being faster and approximately ten times less expensive, PRINS
      can replace FISH for detecting numerical karyotype changes.

PMID- 9196433
TI  - Computerized scene segmentation for the discrimination of architectural features
      in ductal proliferative lesions of the breast.
AB  - The distinction between ductal hyperplasia (DH) and ductal carcinoma in situ
      (DCIS) still remains a problem in the histological diagnosis of non-invasive
      breast lesions. In this study, a method was developed for the automatic
      segmentation and quantitative analysis of breast ducts using knowledge-guided
      machine vision. This permitted duct profiles and intraduct lumina to be
      identified and their shape, size, and number computed. These were used to derive
      measures of duct cribriformity and architectural complexity which were examined
      as an objective tool in the characterization of duct pattern in proliferative
      lesions. A total of 215 images of ducts were digitally captured from 22 cases of
      DCIS and 21 cases of DH diagnosed independently by two pathologists. The
      cribriformity index proved to be a useful measure of duct architecture, showing a
      nosotonic increase with increasing duct complexity. The number of lumins also
      increased with increasing overgrowth of ductal epithelium until the duct was
      filled. Discriminant analysis of the duct characteristics for benign and
      malignant groups selected the lumen area/duct area ratio and the duct area as
      significant discriminatory variables and they were combined into a discriminant
      function. Of the lumens features, the mean area of the lumen and the polar
      average (mean of the distribution of the number of events with an increasing
      spiral from the centre of the duct) were combined into a second discriminant
      function. Plotting cases against these two functions provided good separation of
      DH and DCIS groups, with correct classification estimated on the training sample
      as being over 80 per cent. With an increasing incidence of complex proliferative
      lesions arising from mammography, the ability to diagnose these lesions correctly
      is more important than ever. The use of expert system-guided machine vision
      facilitates the quantitative evaluation of breast duct architecture; along with
      established histological and cytological criteria, it is hoped that this will
      lead to a more objective means of diagnosis and disease classification.

PMID- 9196434
TI  - c-myc gene abnormalities in mucosa-associated lymphoid tissue (MALT) lymphomas.
AB  - c-myc gene abnormalities associated with lymphomagenesis, including
      rearrangements and mutations in the regulatory region between exon I and intron
      I, have been studied in 54 MALT lymphomas (43 low and 11 high grade) and 36 nodal
      lymphomas (27 low and 9 high grade). By Southern blot analysis, none of the 54
      MALT lymphomas but 2 of 36 nodal lymphomas had c-myc gene rearrangements. Defined
      tumour cell populations from all MALT lymphoma cases were isolated by
      microdissection from frozen tissue sections and analysed by polymerase chain
      reaction-single-strand conformational polymorphism (PCR-SSCP) and direct
      sequencing for somatic mutations in the exon I/intron I region of the gene. Point
      mutations in this region were identified in nine cases of MALT lymphomas (7/43 =
      16.2 per cent of low grade; 2/11 = 18.1 per cent of high grade). These mutations
      were located at either the exon I/intron I border of myc intron factor (MIF)
      binding sites, which are critical in the negative regulation of c-myc expression.
      Of the nodal lymphomas, only the two cases (5-6 per cent) with c-myc gene
      rearrangement showed scattered or clustered mutations. These results suggest that
      c-myc mutations in MALT lymphomas are unlikely to be associated with chromosome
      translocation, which is the main cause of somatic mutations observed in other
      types of lymphomas. The mutations involving the c-myc regulatory regions may play
      a pathogenetic role in at least a proportion of MALT lymphomas.

PMID- 9196435
TI  - IgH and TcR-gamma gene rearrangements identified in Hodgkin's disease by PCR
      demonstrate lack of correlation between genotype, phenotype, and Epstein-Barr
      virus status.
AB  - Analysis of IgH and TcR-gamma genes using consensus primers identifying
      junctional regions of rearranged genes by polymerase chain reaction (PCR) was
      performed on tissues involved by Hodgkin's disease (HD) in 90 cases and was
      correlated with the immunophenotype of Hodgkin and Reed-Sternberg (HRS) cells and
      the presence of Epstein-Barr virus (EBV) within these cells. Clonal IgH gene
      rearrangements were found in 1/5 cases of lymphocyte predominance (LP) subtype
      and none was positive for EBV. In 85 cases of classic HD, no IgH or TcR-gamma
      gene rearrangements were found in 51 (60 per cent) cases. A similar percentage,
      but not the same cases, were of null (non-B, non-T) phenotype. Of 30 cases where
      a B phenotype was assigned to HRS cells, nine had IgH gene rearrangements, three
      had TcR-gamma gene rearrangements, and two had both genes rearranged. None of the
      five cases assigned to T phenotype of HRS cells showed rearrangement of TcR-gamma
      genes, but two cases showed rearranged IgH genes. Among 41 cases of null
      phenotype, ten had IgH gene rearrangements, five had TcR-gamma gene
      rearrangements, and three cases had both genes rearranged. Whereas EBV was
      detectable in HRS cells in 17/43 classic HD cases of assigned B phenotype, EBV
      was also detectable in 2/5 cases of assigned T phenotype and in 21 cases with the
      null phenotype. Furthermore, there was no correlation of EBV with the presence or
      lack or IgH or TCR-gamma gene rearrangements. Of the remainder, half (30 per
      cent) expressed antigens associated with lymphocytes without an appropriate
      genotype. The results confirm lymphocyte-lineage committed cells at the origin of
      HRS cells in 40 per cent of cases. Any hypothesis of a non-lymphocytic origin of
      HRS cells will require the inducibility of CD30 on candidate precursors and the
      methodology for probing genetic events in such cells to be addressed.

PMID- 9196436
TI  - Comparative genomic hybridization (CGH) analysis of neuroblastomas--an important
      methodological approach in paediatric tumour pathology.
AB  - Comparative genomic hybridization (CGH) was applied to 35 neuroblastomas to
      obtain a global view of genetic imbalances. Results were validated by means of
      Southern blot hybridization (detection of N-myc amplification), loss of
      heterozygosity (LOH) studies (detection of deletion 1p), and interphase
      cytogenetics [dual labelling fluorescence in situ hybridization (FISH) of
      centromeric 17 and erbB-2]. CGH allowed sensitive detection of N-myc
      amplification and chromosome 1p deletion, representing the most established
      prognostic markers of neuroblastoma. In addition, a high rate of chromosome 17
      aberrations (63 per cent) with possible prognostic relevance was observed.
      Previously unreported high level copy number increases indicating oncogene
      amplification were mapped to chromosome subbands 2p13-14 and 3q24-26. Other
      recurrent regional chromosomal aberrations were localized on 11q, 12q, 13q, 14q,
      and 15q. CGH results were fully consistent with data of Southern blot analysis
      and LOH study, as well as interphase cytogenetics. These results show that CGH is
      a sensitive method for the detection of all prognostically relevant genetic
      alterations in neuroblastomas; that CGH considerably simplifies the detection of
      these alterations, resulting in a single methodological approach; and that CGH is
      a powerful tool to elucidate previously unknown genetic changes in
      neuroblastomas.

PMID- 9196437
TI  - The pattern of K-ras mutation in pulmonary adenocarcinoma defines a new pathway
      of tumour development in the human lung.
AB  - Codon 12 of the K-ras oncogene was screened for mutations in 65 surgically
      resected primary pulmonary adenocarcinomas and in 32 tissue foci of alveolar
      atypical hyperplasia (AAH) by a polymerase chain reaction (PCR)-based method.
      Mutations in either position 1 or position 2 of codon 12 were detected in 16
      tumours (25 per cent). When analysed by site of origin, mutations were seen in
      9/26 (35 per cent) parenchymal and in 0/12 bronchial adenocarcinomas (P < 0-02),
      K-ras mutations were seen in five AAH lesions from four patients. DNA sequencing
      showed that the great majority of mutations in both adenocarcinomas and AAH were
      G-T transversions. These findings provide support for the classification of
      pulmonary adenocarcinomas into bronchial and parenchymal subtypes and also
      provide molecular evidence to support the importance of AAH in the development of
      parenchymal cancers.

PMID- 9196438
TI  - Neurotrophin-3 expression in human pancreatic cancers.
AB  - Some neurotrophic factors stimulate process outgrowth in peripheral and/or
      central nerve fibres. There is no published report that has focused on the
      expression of neurotrophic factors in human pancreatic cancer except basic
      fibroblast growth factor. This study was therefore designed to examine the mRNA
      and protein levels of neurotrophin-3 (NT-3), which is one of the representative
      neurotrophic factors. The mRNA level for NT-3 was first investigated in eight
      pancreatic cancers and two samples of normal pancreas, using reverse
      transcription-polymerase chain reaction (RT-PCR). NT-3 protein expression was
      then studied in 47 human pancreatic cancers, using a monoclonal antibody against
      human NT-3 protein. There was a notable difference in the level of NT-3 mRNA
      between normal and pancreatic carcinoma tissues, with no evident difference in
      the expression of the beta-actin gene. Immunohistochemically, 34 of 47 pancreatic
      cancers (72 per cent) were mildly to markedly immunoreactive for NT-3 in the
      cytoplasma. Immunoreactivity was usually more pronounced at the infiltrative
      margins of the tumours. These observations suggest that pancreatic carcinoma
      overexpresses NT-3.

PMID- 9196439
TI  - Immunohistochemical expression of inhibin/activin subunits in epithelial and
      granulosa cell tumours of the ovary.
AB  - Dimeric inhibin-A has been shown recently by a sensitive two-site ELISA assay to
      be a useful tumour marker in granulosa cell tumours of the ovary. It is also
      elevated in some patients with malignant epithelial ovarian tumours. To identify
      the precise subunits of inhibin expressed in ovarian tumours, three monoclonal
      antibodies, R1, E4, and INPRO (against the alpha C-, beta A-, and pro-alpha
      subunits, respectively), were evaluated by immunohistochemistry on a panel of six
      granulosa cell and nine epithelial tumours. All granulosa cell tumours stained
      positively with E4 and R1, suggesting expression of dimeric inhibin-A; in two
      patients where serum levels were measured pre-operatively, they were elevated.
      The tumours also reacted weakly with INPRO, suggesting the presence of precursor
      forms of the alpha-subunit. Eight malignant epithelial ovarian tumours expressed
      the beta A-subunit only, as recognized by E4, while one tumour expressed both
      alpha- and beta A-subunits, which correlated with an elevated serum inhibin-A
      level. Thus, while granulosa cell tumours express inhibin, the majority of
      epithelial tumours probably express activin, a result which needs to be confirmed
      by serum measurements.

PMID- 9196440
TI  - An immunocytochemical study of MHC class I expression on human Langerhans cells
      and melanocytes.
AB  - Classical MHC class I glycoproteins (HLA-A, B, and C) present endogenous
      cytosolic peptide antigen fragments to CD8-positive T-cells. CD8-positive T-cell
      recognition and destruction of virus-infected cells are dependent on adequate
      cellular MHC class I expression. Constitutive MHC class I expression is
      ubiquitous, but known to be deficient on specific differentiated cell types which
      include hepatocytes, neurones, chondrocytes and myocytes. Although enabling
      assessment of MHC class I expression on individual cells, limitations of
      immunocytochemistry were encountered with this assessment on Langerhans cells and
      melanocytes. These dispersed intraepidermal cells were obscured by adjacent
      keratinocytes in sections immunostained for MHC class I glycoproteins.
      Initiatives designed to resolve the issue have included immunoelectron
      microscopy, cell culture techniques, and animal bone marrow chimera models.
      Despite the elegance of these techniques, the issue of MHC class I expression on
      Langerhans cells and melanocytes remains unresolved. In this immunocytochemical
      study, an alternative strategy was based upon the recognized deficiency of
      epithelial MHC class I expression within pilosebaceous adnexal units. Langerhans
      cells and melanocytes were therefore studied within this microenvironment of
      deficient MHC class I expression, using monomorphic and polymorphic MHC markers.
      Langerhans cells and melanocytes were demonstrated within pilosebaceous units of
      scalp skin by immunocytochemistry. Differentiation markers OKT6 (CD1a) and TMH1
      defined Langerhans cells and melanocytes, respectively. Monomorphic MHC markers
      W6/32 and TAL IB5 defined invariant epitopes of HLA class I and II, respectively.
      Polymorphic MHC class I markers defined the HLA-Bw4 and HLA-Bw6 supertypic
      determinants. Constitutive MHC class I expression was shown to be deficient on
      Langerhans cells and melanocytes.

PMID- 9196441
TI  - APC expression in normal human tissues.
AB  - The tumour suppressor gene APC codes for a 2843-amino acid protein whose precise
      functions are still poorly understood. This paper describes the development of
      two new antisera to APC (to amino- and carboxy-terminal epitopes) which permit
      localization of the protein by immunohistochemistry in archival paraffin
      sections. The protein is expressed in a wide variety of normal epithelial
      tissues. Its distribution frequently coincides with the location of post
      replicative cells within tissues. Staining patterns demonstrate that the APC
      protein, although often diffusely cytoplasmic in distribution, may also
      accumulate in the apical and immediately subapical regions, or along the lateral
      margins of certain cells. These results indicate that APC is significant in many
      tissues in addition to the colorectal epithelium. They are compatible with a
      function related to signalling at the adherens junction and possibly with other
      more complex roles in cells committed to terminal differentiation.

PMID- 9196442
TI  - Glioma invasion in vitro is mediated by CD44-hyaluronan interactions.
AB  - Invasion is a clinically important problem contributing to mortality and
      morbidity in patients with gliomas, but the mechanism(s) by which glioma cells
      invade surrounding brain structures is poorly understood. Various experimental
      models have been used in attempts to elucidate the process of glioma invasion. An
      in vitro model which is increasingly being employed involves measurement of the
      rate of invasion of tumour cells through Matrigel-a complex mixture of
      extracellular matrix components derived from the Engelbroth-Holm-Swarm (EHS)
      sarcoma. This model has been used to examine the possibility that extracellular
      hyaluronan (HA) might facilitate the invasive behaviour of human glioma cells.
      The major component of Matrigel is laminin, with smaller amounts of collagen IV,
      heparan sulphate proteoglycans, entactin, and nidogen but it lacks HA. In our
      experiments, we have incorporated HA into Matrigel and have measured its effect
      on the rate of invasion of human glioma cells in a modified Boyden chamber assay
      system. The incorporation of HA (50-800 mg/cm2) resulted in a dose-dependent
      increase in invasion. Invasion was enhanced by up to 70 per cent in comparison
      with HA-free Matrigel. Since CD44 is a major HA receptor expressed on gliomas, it
      might have a role in the HA-mediated facilitation of invasion. This was tested by
      blocking CD44 with specific antibody, which resulted in a 43 per cent reduction
      in invasion rate. We conclude that in an in vitro model system, HA enhances
      invasion of glioma cells and that the mechanism involves a CD44-HA interaction.

PMID- 9196443
TI  - Studies on the proliferative activity of diethylnitrosamine-induced
      hepatocellular carcinomas in monkeys.
AB  - In this study, synthetic phase fractions (SPFs) determined by flow cytometry and
      AgNOR counts were analysed in benign liver lesions (regenerative nodules and
      adenomas), hepatocellular carcinomas (HCCs), and lung metastases of a monkey
      hepatocarcinogenesis model to find out if AgNOR counts and SPFs can discriminate
      between malignant and non-malignant liver lesions. The average per cent SPF
      values and the AgNOR counts were significantly (P = 0.001) increased in
      regenerative liver nodules (5.30 per cent; 4.96), adenomas (5.34 per cent; 3.46)
      and well-differentiated HCCs (6.75 per cent; 4.47), compared with the untreated
      control livers (3.18 per cent; 0.98), but the differences between these three
      groups were not significant. In the poorly differentiated HCC group, however, the
      average SPF value (9.60 per cent) and AgNOR count (7.14) were significantly
      higher than in any of the other liver lesions examined. A significant correlation
      was found between the SPF values and AgNOR counts on the one hand, and
      differentiation and cytological grade of the HCC samples on the other. The
      results of this study show that the SPF values and AgNOR counts are not reliable
      in differentiating between regenerating liver nodules, adenomas, and experimental
      well-differentiated HCCs. The SPF value, however, may serve as a prognostic
      factor in HCC, since it was found to be significantly higher in HCCs with lung
      metastasis than in those without.

PMID- 9196444
TI  - Increased expression of IL-15 in the synovium of patients with rheumatoid
      arthritis compared with patients with Yersinia-induced arthritis and
      osteoarthritis.
AB  - Recently, a new player in the cytokine network has been described that is
      produced by monocytes and can be detected in the rheumatoid synovium: interleukin
      15 (IL-15). Since this cytokine may play a role in the accumulation and
      activation of T-cells, B-cells, and natural killer (NK) cells characteristic of
      synovial tissue (ST) from patients with rheumatoid arthritis (RA), the expression
      of IL-15 was studied in ST from RA patients in comparison with ST from patients
      with reactive arthritis (ReA) and osteoarthritis (OA) and the phenotype of IL-15
      positive cells was determined. IL-15 expression was investigated by
      immunohistochemical analysis of ST from ten patients with RA, ten patients with
      Yersinia enterocolitica-induced ReA, and nine patients with OA. The
      immunohistological findings were quantified and the results obtained in the
      different patient groups were compared. To determine the phenotype of IL-15
      expressing cells, double-labelling immunofluorescence was performed. The
      expression of IL-15 was significantly higher in ST from patients with RA than in
      ST from patients with ReA or OA. In double-label experiments, co-expression was
      observed with markers for macrophages, T-cells, and NK cells. The composition of
      the cellular infiltrate in the synovium of patients with RA might be partly
      explained by the specific increase in expression of IL-15 in rheumatoid ST. It
      can be speculated that IL-15 production by inflammatory cells other than
      macrophages may occur in the rheumatoid synovium.

PMID- 9196445
TI  - Three-dimensional reconstruction of non-Hodgkin's lymphoma in bone marrow
      trephines.
AB  - The objective of this study was to analyse the location in the bone marrow of
      deposits of low-grade non-Hodgkin's lymphoma. This was achieved using computer
      generated three-dimensional reconstruction techniques applied to serial tissue
      sections of five bone marrow trephines involved by lymphoma. For comparative
      purposes, previously published three-dimensional models of benign lymphoid
      aggregates in the bone marrow were need. The images generated by this new study
      showed that deposits of low-grade non-Hodgkin's lymphoma involving the bone
      marrow always assumed a paratrabecular pattern of infiltration at some point.
      This is in direct contrast to the pattern of bone marrow infiltration shown by
      benign lymphoid aggregates. It is concluded that location within the marrow space
      is a crucial factor in distinguishing between benign and low-grade malignant
      lymphoid infiltrates in the bone marrow.

PMID- 9196446
TI  - Characterization of renal angiomyolipoma by scanning acoustic microscopy.
AB  - A scanning acoustic microscope system was used to differentiate renal
      angiomyolipoma from renal cell carcinoma. The ultrasonic frequency used ranged
      from 100 to 200 MHz, and the attenuation constant and sound speed were measured
      on a two-dimensional distribution. The sound speed was significantly lower for
      lipoma cells than for vessels, smooth muscle fibres, clear cell renal cancer or
      granular cell renal cancer. The attenuation constant was significantly lower for
      lipoma cells than for vessels or clear cells. Both acoustic parameters for smooth
      muscle fibres were significantly lower than for vessels. The heterogeneity of the
      microacoustic field in renal angiomyolipoma is closely related to the high
      intensity echo observed on clinical echography. Renal angiomyolipoma and renal
      cell carcinoma can thus be distinguished by acoustic examination.

PMID- 9196447
TI  - CD45 immunostaining in T-cell-rich B-cell lymphoma and lymphocyte predominance
      Hodgkin's disease.

PMID- 9196448
TI  - Time to pregnancy: a measure of reproductive function in either sex. Asclepios
      Project.
AB  - INTRODUCTION: Growing evidence of reproductive effects associated with
      occupational and environmental agents has created the need for research with
      sensitive and well validated methods. There is a complex relation between
      manifest effects and underlying pathogenic processes. Conceptions will on average
      tend to be delayed in a population exposed to an agent that causes embryonic
      damage, an increase in germ cell mutations, or decreased fertility. STUDYING TIME
      TO PREGNANCY: Time to pregnancy can be used to measure the degree of delay in
      conceiving, across the whole continuum of biological fertility, in either men or
      women. The distribution of time to pregnancy largely reflects a sorting process,
      as the more fertile couples become progressively less well represented with the
      passage of time. The basic research strategy is comparison of the time to
      pregnancy within groups defined by their exposures, allowing for potential
      confounding factors relating not only to the study subject but also to his or her
      partner. MEASUREMENT AND VALIDITY: Prospective and retrospective methods are
      available, and each has strengths and weaknesses. Prospective studies have some
      theoretical advantages, but have unrepresentative populations and problems of
      feasibility and cost. Retrospective assessment of time to pregnancy is feasible
      with a short questionnaire, without intruding into sensitive areas of
      respondents' lives, with good validity at the group level, and without the
      necessity of large populations. Potential biases have been identified that can be
      minimised by careful design and analysis; the principal remaining problem is
      difficulty in obtaining exposure data retrospectively.

PMID- 9196449
TI  - Changes in respiratory function after one and three hours of exposure to
      formaldehyde in non-smoking subjects.
AB  - OBJECTIVE: To determine the changes in respiratory function within one hour and
      three hours of exposure to formaldehyde and investigate the relation between
      exposure to formaldehyde and acute changes in respiratory function. METHOD:
      Respiratory function of 50 non-smoking medical students exposed to formaldehyde
      in a gross anatomy laboratory were compared with respiratory function of 36 non
      exposed, non-smoking physiotherapy students. Formaldehyde concentrations were
      measured in the breathing zone of each exposed subject and in the general work
      environment. RESULTS: Formaldehyde concentrations in the breathing zone of
      exposed subjects generally exceeded recommended standards. On average, the
      variables of respiratory function of both the exposed and the control subjects
      increased significantly within one hour and from one to three hours after
      exposure. The increase in respiratory function of the exposed subjects was
      significantly less than that of the control subjects. There was no meaningful
      correlation between concentration of formaldehyde in the breathing zone and
      changes in the respiratory function of exposed subjects. CONCLUSION: As the
      increase in the respiratory function of the subjects can be attributable to
      normal diurnal variation, the significantly lower increase in respiratory
      function of the exposed group than in the control group is probably due to
      exposure to formaldehyde. The results of this study do not, however, support a
      dose-response relation.

PMID- 9196451
TI  - Structural nerve changes at wrist level in workers exposed to vibration.
AB  - OBJECTIVES: To analyse the character of morphological changes occurring in a well
      defined peripheral nerve in humans exposed to vibration from hand held tools.
      METHODS: Biopsies of the dorsal interosseus nerve just proximal to the wrist were
      taken from 10 men exposed to vibration and from 12 male age matched necropsy
      controls. The nerve was resected for pain relief either as the sole procedure or
      in conjunction with carpal tunnel release. All specimens were sectioned and
      examined by light microscopy in standard sections, thin epon sections, and
      teasing preparations. RESULTS: The combined results of the analyses showed
      pathological changes in all 10 patients dominated by breakdown of myelin and by
      interstitial and perineurial fibrosis. All but one of the 12 controls were
      normal. CONCLUSION: These findings often show severe nerve injury previously not
      described at this level. They indicate that demyelination may be the primary
      lesion in neuropathy induced by vibration followed by fibrosis associated with
      incomplete regeneration or with organisation of oedema. Vibration can induce
      structural changes in peripheral nerves just proximal to the wrist and such
      changes may constitute a structural component in carpal tunnel syndrome among
      people exposed to vibration. This may help to explain the poor results achieved
      by carpal tunnel release in these patients.

PMID- 9196450
TI  - Occupational asthma in New Zealanders: a population based study.
AB  - OBJECTIVES: To examine the effect of occupation on respiratory symptoms in a
      randomly selected adult population aged 20-44 years. METHODS: It is based on the
      phase II sampling of the New Zealand part of the European Community respiratory
      health survey. 1609 people (63.9% response rate) completed a detailed respiratory
      questionnaire. Of those responding, 1174 (73%) underwent skin tests and 1126
      (70%) attended to undergo methacholine bronchial challenge. Current occupation
      was recorded and a previous occupation was also recorded if it had led to
      respiratory problems. 21 occupational groups were used for analysis for the five
      definitions of asthma wheezing in the previous 12 months; symptoms related to
      asthma; bronchial hyperresponsiveness (BHR); BHR with wheezing in the previous 12
      months; and BHR with symptoms related to asthma. RESULTS: Prevalence odds ratios
      (ORs) were significantly increased for farmers and farm workers (OR 4.16, 95%
      confidence interval (95% CI) 1.33 to 13.1 for the combination of wheezing and
      BHR). Increased risks of prevalence of asthma were also found for laboratory
      technicians, food processors (other than bakers), chemical workers, and plastic
      and rubber workers. Workers had also been divided into high and low risk exposure
      categories according to relevant publications. The prevalence of wheezing was
      greater in the high risk group (OR 1.57, 95% CI 0.83 to 2.95) than in the low
      risk group. Atopy was associated with asthma, but the prevalence of atopy did not
      differ significantly between occupational exposure groups. The attributable risk
      of wheezing that occurred after the age of 15 years and that was estimated to be
      due to occupational exposure (based on the defined high risk group) was 1.9%, but
      this increased to 3.1% when farmers and food processors (other than bakers) were
      also included in the high risk group. CONCLUSIONS: This population based study
      has identified certain occupations significantly associated with combinations of
      asthmatic symptoms and BHR.

PMID- 9196453
TI  - Occupational factors related to shoulder pain and disability.
AB  - OBJECTIVES: To determine, in a population based study, the influence of
      occupational factors on the occurrence of shoulder pain and disability. METHODS:
      A random sample of patients was selected from the register of a general practice
      in the Greater Manchester area of the United Kingdom. Information was collected
      by a posted questionnaire with specific enquiries about symptoms in the shoulder
      region and related disability. A lifetime occupational history was obtained
      including physical exposures, working conditions, and psychosocial aspects of
      each workplace. Analysis has been conducted as a case-control study, comparing
      occupational exposures at the time of onset of symptoms in those with shoulder
      pain and disability with corresponding occupational exposures in those without
      shoulder pain and disability. RESULTS: An increased risk of shoulder pain and
      disability in men was associated with carrying weights on one shoulder (relative
      risk (RR) 5.5, 95% confidence interval (95% CI) 1.8 to 17), whereas those who
      reported working with hands above shoulder level, using wrists or arms in a
      repetitive way, or stretching down to reach below knee level had about twice the
      risk of shoulder pain and disability. Men working frequently in very cold or damp
      conditions had a fourfold and sixfold risk respectively of shoulder pain and
      disability. Reporting of shoulder pain and disability was also more common among
      men and women who reported that their work caused a lot of stress (RR 1.9, 95% CI
      0.9 to 4.1) or was very monotonous (RR 2.7, 95% CI 1.3 to 5.4). The relations
      between physical exposures, working conditions, and psychosocial factors were
      independent. CONCLUSIONS: This population based study has shown that physical
      activities carried out at work, the physical conditions under which the work is
      conducted, psychosocial aspects of work, or the working environment are all
      independently related to the occurrence of shoulder symptoms and disability,
      emphasising the multifactorial nature of this condition.

PMID- 9196452
TI  - Nerve injury induced by vibration: prevention of the effect of a conditioning
      lesion by D600, a Ca2+ channel blocker.
AB  - OBJECTIVES: Exposing a hind leg of a rat to vibration induces an injury to the
      sciatic nerve--a so called conditioning lesion. After such injury induced by
      vibration the regenerative capacity of the nerve is improved and can be detected
      as an increased axonal outgrowth from a test crush lesion to the same nerve. The
      purpose was to study whether the effect of a conditioning lesion induced by
      vibration can be prevented by local treatment with a Ca2+ channel blocker D600.
      METHODS: D600 (methoxyverapamil) or Ringer's solution was locally applied to the
      sciatic nerve on one side through a silicone tube connected to a miniosmotic
      pump, which was implanted subcutaneously. During the same period the hind leg was
      exposed to vibration (80 Hz; 32 m/s2 root mean squared) for five hours daily for
      five consecutive days. The other hind leg was not vibrated. After the end of
      exposure to vibration the sciatic nerves were crushed bilaterally (test crush
      lesions) and three or six days later the regeneration distances of sensory axons
      were measured by the pinch reflex test. RESULTS: Nerves in the control animals
      (without implanted miniosmotic pumps and nerves on to which Ringer's solution was
      locally applied) that were exposed to vibration showed a significantly increased
      outgrowth length of sensory axons from the test crush lesion compared with the
      non-vibrated side. Such an effect of a conditioning lesion from the exposure to
      vibration was suppressed by local application of D600. CONCLUSIONS: Local
      administration of a Ca2+ channel blocker D600 can prevent the effect of a
      conditioning lesion-that is, the nerve injury induced by vibration can be
      inhibited by D600. This may have implications for the treatment of patients with
      neuropathy of the hand induced by vibration.

PMID- 9196454
TI  - Humidification and perceived indoor air quality in the office environment.
AB  - OBJECTIVE: To evaluate the effect of humidification on the odour, acceptability,
      and stuffiness of indoor air. METHODS: In a six period cross over trial at the
      Pasila Office Center, Helsinki, the air of two wings of the building in turn were
      ventilated with air of 30%-40% humidity. A third wing served as a non-humidified
      control area. The quality of indoor air was assessed weekly by a panel containing
      18 to 23 members. The intraindividual differences in the ratings for odour,
      stuffiness, and acceptability between humidified and non-humidified wings were
      used to assess the effect of humidification. The roles of sex, current smoking,
      and age as potential effect modifiers were assessed by comparing the mean
      intraindividual differences in ratings between the groups. RESULTS: Humidified
      air was found to be more odorous and stuffy (paired t test P = 0.0001) and less
      acceptable than the non-humidified air (McNemar's test P < 0.001). The
      differences in odour and stuffiness between humidified and non-humidified air
      were greater for women and for non-smokers, and greatest differences were in the
      youngest age group, and least in the oldest age group. The differences were not
      significant. CONCLUSIONS: An untrained panel of 20 members is able to
      differentiate a slight malodour and stuffiness in indoor air. The results suggest
      that steam air humidification decreases the perceived air quality. This effect is
      strongest in women and young subjects.

PMID- 9196455
TI  - Relapse and short sickness absence for back pain in the six months after return
      to work.
AB  - OBJECTIVES: To measure the incidence of back pain relapse (causing three
      consecutive days off work on medical advice) and of short sickness absence (less
      than three consecutive days), and to determine whether the incidence of such
      events was affected by overall pain and specific pain related to simple daily
      movements (functional capacity) assessed at discharge. METHODS: A cohort of
      workers with a first compensated episode of back pain was prospectively followed
      up from return to work after rehabilitative treatment. Follow up among 230
      workers was carried out monthly by phone for a maximum of six months. Crude and
      adjusted rate ratios (RRs) along with 95% confidence intervals (95% CIs) were
      estimated with the Cox's proportional hazards model. RESULTS: Within six months
      of return to work, 29 workers (12.6%) had relapsed, and another 15 workers (6.5%)
      had a short sickness absence. 50% of relapses had occurred within 42 days of
      return to work whereas this figure was 28 days for short sickness absence. In a
      multivariate model that considered pain and clinical variables at discharge only
      a scale combining all pain variables (specific daily movements as well as the
      visual analog overall pain scale) contributed to relapse and short sickness
      absence as the outcome (RR (95% CI)) (1.53 (0.96-2.43)); the same was true in a
      model considering pain and workers' views on desired changes to work conditions
      (1.60; 1.08 to 2.36). CONCLUSIONS: Incidence of relapse or short sickness absence
      in the first six months after return to work was 19.1%. Of all measured
      prognostic variables (sociodemographic, clinical, workers' views, and pain), only
      overall pain and pain associated with carrying out simple daily movements were
      helpful in predicting relapse or short sickness absence.

PMID- 9196456
TI  - Latex allergy: epidemiological study of 1351 hospital workers.
AB  - OBJECTIVE: To determine the prevalence of latex sensitisation among a large group
      of healthcare workers, study the occupational and non-occupational factors
      associated with latex allergy, and characterise latex exposure in air and by
      gloves. METHODS: All 2062 employees of a general hospital in Hamilton, Ontario,
      Canada who regularly used latex gloves were invited to participate in a cross
      sectional survey, representing the baseline phase of a prospective cohort
      morbidity study. Attempts were made to recruit employees who were diagnosed with
      latex allergy before the survey. Glove extracts were assayed for antigenic
      protein, and area and personal air samples were obtained on two occasions (summer
      and winter) to estimate exposure to airborne latex protein. A questionnaire on
      medical and occupational information was administered by an interviewer. Skin
      prick tests were performed with latex reagents, three common inhalants, and six
      foods. RESULTS: The mean (SD) latex protein concentrations were 324 (227)
      micrograms/g in powdered surgical gloves and 198 (104) micrograms/g in powdered
      examination gloves. Personal latex aeroallergen concentrations ranged from 5 to
      616 ng/m3. There was a total of 1351 (66%) participants. The prevalence of
      positive latex skin tests was 12.1% (95% confidence interval (95% CI) 10.3% to
      13.9%). This prevalence did not vary by sex, age, hospital, or smoking status but
      subjects who were latex positive were significantly more likely to be atopic (P <
      0.01). Participants who were latex positive were also significantly more likely
      to have positive skin tests to one or more foods (Mantel-Haenszel odds ratio (OR)
      adjusted for atopy 12.1, 95% CI 7.6 to 19.6, P < 10(-9)). Work related symptoms
      were more often reported among latex positive people, and included hives (OR 6.3,
      95% CI 3.2 to 12.5), eye symptoms (OR 1.9, 95% CI 1.2 to 2.8), and wheezy or
      whistling chest (OR 4.7, 95% CI 2.8 to 7.9). The prevalence of latex sensitivity
      was highest among laboratory workers (16.9%), and nurses and physicians (13.3%).
      When the glove consumption per healthcare worker for each department was grouped
      into tertiles, the prevalence of latex skin test positivity was greater in the
      higher tertiles of glove use for sterile (surgical) gloves (P < 0.005) but not
      for examination gloves. CONCLUSIONS: In this large, cross sectional study of
      healthcare workers, the prevalence of latex sensitisation was 12.1% (9.5% among
      all those eligible), and there were significant associations with atopy, positive
      skin tests to certain foods, work related symptoms, and departmental use of
      gloves per healthcare worker. This cohort is being followed up prospectively and
      will be retested to determine the incidence of development of latex sensitivity.

PMID- 9196458
TI  - Study of business ethics in occupational medicine.
AB  - OBJECTIVE: To investigate the views of specialists in occupational medicine about
      business ethics in occupational medicine. METHOD: A qualitative study with face
      to face focus groups and successive reviews of the draft consensus was undertaken
      of all accredited specialists in occupational medicine who were members of the
      south Wales and west of England group of the Society of Occupational Medicine,
      and of all regional specialty advisers and deputies from the Faculty of
      Occupational Medicine. RESULTS: There was widespread agreement for the need of a
      code of business ethics. In all, during the four draft stages of preparing a
      consensus, 72% (28/39) of members of the south Wales and west of England group of
      the Society of Occupational Medicine, and 31% (20/64) of regional specialty
      advisers and deputies provided detailed comment for inclusion in it. CONCLUSIONS:
      Consensus of their views was reached among study participants for issues of
      business ethics involving advertising, competence, qualifications, fees,
      commitment, changes in provider contracts, regulation, and supervision of
      trainees. It provides a basis for further debate.

PMID- 9196459
TI  - A bibliometric study of the trend in articles related epidemiology published in
      occupational health journals.

PMID- 9196457
TI  - Evaluation of the Q16 questionnaire on neurotoxic symptoms and a review of its
      use.
AB  - OBJECTIVES: The questionnaire 16 (Q16) is commonly used to study prevalences of
      neurotoxic symptoms among workers exposed to organic solvents. It has also been
      recommended that exposed workers reporting more than six symptoms should be
      referred for further examination of possible chronic toxic encephalopathy. It
      would be useful to know whether symptoms reported in the questionnaire also
      reflect impairment of similar functions measured with objective or semiobjective
      methods in a formerly highly exposed group. METHODS: 135 painters and 71
      carpenters answered the Q16, were interviewed about symptoms compatible with an
      organic brain damage, and took a battery of psychometric tests. A subsample of 52
      painters and 45 carpenters were interviewed for psychiatric diagnosis according
      to Diagnostic and Statistical Manual for Mental Disorders, 3rd version (DSM III)
      and their vibration thresholds in hands and feet were measured. The entire group
      was followed up in the register of diagnoses at early retirement 1971-93. The
      lifetime exposure to organic solvents was assessed. Current exposure to organic
      solvents was found to be low or none. RESULTS: The prevalence of people with more
      than six symptoms in the Q16 rose with increasing cumulative exposure to
      solvents. The sensitivity of the questionnaire (more than six symptoms) to detect
      people who were assessed to exhibit symptoms compatible with an organic brain
      damage was only 38%. One of seven people who had retired early with a diagnosis
      compatible with a chronic toxic encephalopathy, and two of five people with a
      psychiatric diagnosis compatible with this condition, had more than six symptoms
      in the Q16. The agreement between Q16 replies and psychometric test results, as
      well as other examinations, was low. CONCLUSIONS: The notable exposure-response
      relation indicates that the questionnaire is useful for comparison of groups with
      different exposures to organic solvents. There was low agreement between the
      number of symptoms on the questionnaire and the assessment of symptoms compatible
      with organic brain damage, as well as psychiatric, or early retirement diagnoses
      compatible with chronic toxic encephalopathy. The questionnaire does not seem
      useful for screening of patients with chronic toxic encephalopathy in groups
      without ongoing exposure to organic solvents.

PMID- 9196460
TI  - The influence of retained mass (lung burden) on the results of intratracheal
      tests.

PMID- 9196461
TI  - Electromagnetic fields and cancer: incorrect citations.

PMID- 9196462
TI  - Does folk medicine work? A randomized clinical trial on patients with prolonged
      back pain.
AB  - OBJECTIVE: To determine whether traditional bone-setting or continuous light
      exercise therapy could case back pain and improve function better than ordinary
      physiotherapy. DESIGN: Observer-blinded, randomized clinical trial with a 6-month
      follow-up. SETTING: An outpatient institution for folk medicine research.
      PATIENTS: Of 147 back pain patients recruited from local health centers and by
      newspaper announcements, 132 were found eligible (non-retired-no
      contraindications to manipulation) and entered. A final 114 (one dropout) with
      back pain for longer than 7 weeks were included in this intent to treat analysis.
      INTERVENTIONS: Bone-setting, guidance for continuous light back movements or
      physiotherapy for up to ten 1-hour sessions during 6 weeks. MAIN OUTCOME
      MEASURES: Spinal mobility and muscular performance. Back pain assessed by visual
      analog scales (VAS). RESULTS: The physical measures changed only modestly, from
      one tenth to half of standard deviation, while the VAS was halved. The
      thoracolumbar side-bending, the modified Schober, and the VAS were significantly
      better improved by bone-setting than by exercise but not better than by
      physiotherapy. CONCLUSION: Neither bone-setting nor exercise differed
      significantly from physiotherapy, but bone-setting improved lateral and forward
      bending of the spine and back pain more than did exercise.

PMID- 9196463
TI  - An electroencephalographic study of imagined movement.
AB  - OBJECTIVE: Determine the generator sources for actual and imagined (simulated)
      movements of fingers and toes. DESIGN: Observational. SETTING:
      Electroencephalography laboratory. SUBJECTS: Ten asymptomatic adult volunteers.
      MAIN OUTCOME MEASURE: Comparison of cortical electrical fields and their dipole
      sources in actual and imagined movements. RESULTS: Cortical electrical fields
      tend to be contralateral with actual movements and midline with imagined
      movements. Dipole sources of actual movements include a contralateral
      contribution from the frontal (primary motor) area. Sources of imagined movements
      are midline or ipsilateral. CONCLUSIONS: (1) The motor networks underlying the
      generation of actual and imagined movements are different. (2) Imagined movements
      lack a primary motor area source, but involve medial and ipsilateral structures.
      (3) The effectiveness of imagined movements in rehabilitation may stem from
      activation of premotor or supplementary motor areas.

PMID- 9196464
TI  - Reciprocating gait orthoses: a multicenter study of their use by spinal cord
      injured patients.
AB  - OBJECTIVE: Use of reciprocating orthosis (RGO, ARGO, HGO) by 74 patients with
      complete traumatic spinal cord injury was studied. Lesion levels ranged from T1
      to T12. STUDY DESIGN: Patients were enrolled in seven Italian rehabilitation
      centers an average of 37 weeks after acute trauma. The training period averaged
      39 days. Discontinued use of the device was recorded at follow-up. Before
      discharge, functional walking, gait velocity, donning and doffing time, and the
      ability to climb stairs were recorded. The same items were evaluated at 6-month
      follow-up. RESULTS: At follow-up, 24 patients had abandoned the orthosis, 19 used
      the device for therapeutic exercise, 31 used it for functional gait, and 9 also
      used it outside the home. Functional walking was correlated with age, level of
      lesion, ability to climb stairs, duration of training, and lapse of use of the
      orthosis. The results showed a correlation between use of the orthosis and the
      ability to climb stairs, as well as a high Garrett score. CONCLUSION: This
      orthosis is not considered as an alternative to the wheelchair, despite its
      greater speed, simplicity of use, and greater autonomy provided to the user.

PMID- 9196465
TI  - Balance screening of an inner city older adult population.
AB  - OBJECTIVE: Until recently, studies of balance abilities were conducted on nursing
      home residents or volunteers in a clinical laboratory setting. Little is known
      about balance abilities of older adults living independently in large urban
      cities or who represent different ethnic backgrounds. The purpose of this study
      was to describe balance abilities in these individuals. SUBJECTS: Older adults (n
      = 251) ranging in age from 60 to 95 years of age (X = 74.3, SD = 7.7)
      participated. The majority of individuals (85.7%) were African-American or
      Hispanic. PROCEDURE: The elders were screened for past and current medical
      conditions, activity level, and confidence in performing interactions with the
      environment (instrumental activities of daily living), and were administered the
      Berg Balance Scale, Timed Up and Go, and Reach in Four Directions Test. RESULTS:
      The mode on the Berg Balance Scale was 53 (maximum 56). Mean on the Timed Up and
      Go was 15 seconds, and Reach in Four Directions Test was: forward, 8.9 in;
      backward, 4.6 in; right, 6.8 in; and left 6.6 in. Multiple regression analysis
      revealed that the frequency of performing activities and the comfort in
      performing activities without fear of falling significantly contributed to the
      scores on the balance tests. The results of this study can serve as norms for
      balance testing in urban-dwelling older adult populations from diverse
      backgrounds and may be useful for clinicians who are developing health promotion
      and fall prevention programs.

PMID- 9196466
TI  - Readiness to change alcohol drinking habits after traumatic brain injury.
AB  - OBJECTIVE: To describe how motivated are persons with recent traumatic brain
      injury (TBI) to change their alcohol drinking habits and what factors affect
      their motivation. DESIGN: Survey. SETTING: Acute inpatient rehabilitation
      program. PATIENTS: Subjects were 50 patients with recent TBI during inpatient
      rehabilitation. MAIN OUTCOME MEASURES: Readiness to Change (RTC) questionnaire,
      Michigan Alcoholism Screening Test (MAST), and alcohol use questions. RESULTS:
      Subjects were 36 years old; 86% were men. Eighty-four percent fell in the
      contemplation or action phases. Comparisons with a separate medical patient
      sample suggested that TBI may be associated with greater contemplation of change
      and greater readiness to take action to change alcohol use. Multivariate analyses
      indicated that within the TBI sample a positive history of alcoholism, alcohol
      involved in the accident, and higher daily consumption were associated with
      greater readiness to change (especially contemplation scores). CONCLUSIONS: Soon
      after TBI, drinkers frequently contemplate changing their alcohol use. This
      situation may represent an underutilized window of opportunity to reduce
      postinjury alcohol use and abuse. Motivational interviewing techniques seem well
      suited to facilitate change during this period.

PMID- 9196467
TI  - Implanted functional electrical stimulation hand system in adolescents with
      spinal injuries: an evaluation.
AB  - OBJECTIVE: To study the utility and functional benefits of an implanted
      functional electrical stimulation (FES) system for hand grasp and release in
      adolescents with tetraplegia secondary to spinal cord injuries. DESIGN:
      Intervention study with before-after trial measurement with each subject as his
      or her own control. SETTING: Nonprofit pediatric orthopedic rehabilitation
      facility specializing in spinal cord injury. PARTICIPANTS: A convenience sample
      of five adolescents between 16 and 18 years of age with C5 or C6 level
      tetraplegia at least 1 year after traumatic spinal cord injury. Key muscles for
      palmar and lateral grasp and release were excitable by electrical stimulation.
      INTERVENTIONS: A multichannel stimulator/receiver and eight electrodes were
      surgically implanted to provide stimulated palmar and lateral grasp and release.
      In conjunction with implantation of the FES hand system, surgical reconstruction
      in the form of tendon transfers, tendon lengthenings and releases, and joint
      arthrodeses was performed to augment stimulated hand function. Rehabilitation of
      the tendon transfers and training in the use of the FES hand system were
      provided. MAIN OUTCOME MEASURES: Measurements of pinch and grasp force, the Grasp
      and Release Test (GRT), and an assessment of six activities of daily living (ADL)
      were administered before implantation of the FES hand system and at regular
      follow-up intervals. Results of the stimulated response of individual muscles and
      surgical reconstruction were evaluated using standard and stimulated muscle
      testing techniques and standard assessment of joint range of motion. All subjects
      completed followup testing. RESULTS: Lateral and palmar forces were significantly
      greater than baseline forces (p = .043). Heavy objects on the GRT could only be
      manipulated with FES, and FES increased the level of independence in 25 of 30 ADL
      comparisons (5 subjects, 6 activities) as compared to baseline. After training,
      FES was preferred in 21 of 30 comparisons over the typical means of task
      completion. Of the 40 electrodes implanted, 37 continue to provide excellent
      stimulated responses and all of the implanted stimulators have functioned without
      problems. The surgical reconstruction procedures greatly enhanced FES hand
      function by either expanding the workspace in which to utilize FES (deltoid to
      triceps transfer), stabilizing the wrist (brachioradialis to wrist extensor
      transfer), or stabilizing joints (intrinsic tenodesis transfer, FPL split
      transfer). CONCLUSION: For five adolescents with tetraplegia, the combination of
      FES and surgical reconstruction provided active palmar and lateral grasp and
      release. Laboratory-based assessments demonstrated that the FES system increased
      pinch force, improved the manipulation of objects, and typically increased
      independence in six standard ADL as compared to pre-FES hand function. The study
      also showed that the five adolescents generally preferred FES for most of the ADL
      tested. Data on the benefits of the implanted FES hand system outside of the
      laboratory are needed to understand the full potential of FES.

PMID- 9196468
TI  - The bionic glove: an electrical stimulator garment that provides controlled grasp
      and hand opening in quadriplegia.
AB  - OBJECTIVE: This report describes the operation of the Bionic Glove, a new
      functional electrical stimulation (FES) device designed to improve the function
      of the paralyzed hand after spinal cord injury (SCI) or stroke. DESIGN: Signals
      from a sensor in the glove detecting voluntary wrist movement are used to control
      FES of muscles either to produce hand-grasp or to open the hand. When the glove
      is donned, conductive areas on its inside surface automatically make contact with
      self-adhesive electrodes on the skin. SETTING AND PATIENTS: This report concerns
      nine people with SCI who have used the device in their daily lives for up to a
      year or more. Measurements were made at clinics in Edmonton, Miami, and Chicago
      as part of a multicenter clinical trial. OUTCOME MEASURES AND RESULTS: The mean
      peak force of tenodesis grasp in the nine subjects increased from 2.6N (passive)
      to 11.3N (glove active). Active force was significantly greater than passive
      grasp force even when muscles were fatigued after repetitive grasp-release
      cycles. Most manual tasks improved significantly with the use of the glove, as
      judged by the number of tasks completed in a minute or the subjects' qualitative
      ratings of task difficulty. CONCLUSION: The Bionic Glove can provide significant
      improvement of hand function in people with C6-C7 SCI.

PMID- 9196469
TI  - The Arm Motor Ability Test: reliability, validity, and sensitivity to change of
      an instrument for assessing disabilities in activities of daily living.
AB  - OBJECTIVE: To continue and expand determination of the reliability, validity, and
      sensitivity to change of the Arm Motor Ability Test (AMAT), an instrument for
      assessing deficits in activities of daily living (ADL). DESIGN: The AMAT was
      administered twice to patients, with an interest interval of either 1 or 2 weeks,
      by one of two examiners assigned to patients in counterbalanced order. Patients'
      interest intervals and scores on the arm portion of the Motricity Index was
      unknown to the raters. SETTING: A referral inpatient neurological rehabilitation
      center. PATIENTS: Thirty-three subacute stroke inpatients with moderate to mild
      upper extremity motor deficit: median Motricity-Index-Arm score = 89, median
      chronicity = 43d, median age = 66yr; 12 were women. MAIN OUTCOME MEASURE AND
      RESULTS: The AMAT was developed in 1987, and interrater reliabilities at that
      time were found to range from .95 to .99. The present values for interrater
      reliability (2 scales) from videotaped test performance were: kappas = .68 to
      .77. Spearman correlations = .97 to .99. For performance time, interscorer
      reliability from videotaped test performance was .99. Homogeneities for the three
      AMAT measures for the total sample (Cronbach's alpha and split-half reliability)
      were .93 to .99. The test-retest reliabilities for the total sample were .93 to
      .99. The correlations to the Motricity-Index-Arm score were .45 to .61. The AMAT
      detected the difference in change occurring as a result of the passage of 1
      versus 2 weeks in these subacute inpatients, presumably as a result of intensive
      therapy and/or spontaneous recovery, confirming the results of an earlier
      intervention study. CONCLUSION: The AMAT is an instrument with high interrater
      reliability, internal consistency, and sensitivity to change, as well as having
      satisfactory concurrent validity.

PMID- 9196470
TI  - Prescribed versus actual length of stay and inpatient neurorehabilitation outcome
      for brain dysfunctional patients.
AB  - OBJECTIVE: To determine (1) whether brain dysfunctional patients have better
      rehabilitation outcomes if they receive prescribed length of stay (LOS) versus
      less than prescribed and (2) if LOS and cognitive status relate to goal
      attainment. DESIGN: Prospective inception cohort study. STUDY SETTING: Medical
      center and a neurological institute. PARTICIPANTS: One hundred six patients with
      acute static brain lesions. MAIN OUTCOME MEASURES: Documentation of goal
      attainment at discharge and maintenance of goals 6 months after discharge. All
      subjects also received neuropsychological tests at admission and discharge.
      RESULTS: Patients who received prescribed LOS achieved their rehabilitation goals
      at discharge more frequently than patients who received less than prescribed LOS.
      There was, however, no difference between groups as to maintenance of
      rehabilitation goals 6 months after discharge. There was no relation between
      number of days spent in neurorehabilitation and number of goals achieved at
      discharge. Cognitive status at discharge was strongly related to achieving
      rehabilitation goals. CONCLUSION: Although LOS may not specifically relate to
      goal attainment in a heterogeneous group of brain dysfunctional patients,
      patients who receive the prescribed LOS and who show notable improvement in
      cognitive status tend to achieve rehabilitation goals, compared with patients who
      do not.

PMID- 9196471
TI  - Functional measures of first-stroke rehabilitation inpatients: usefulness of the
      Functional Independence Measure total score with a clinical rationale.
AB  - OBJECTIVE: The Functional Independence Measure (FIM) was used to measure function
      in first-stroke patients on admission to and discharge from a rehabilitation
      center, and to determine gain; all data were analyzed by a clinically oriented
      approach. DESIGN: All patients admitted after a first supratentorial stroke to a
      comprehensive rehabilitation facility over a 2-year period were examined
      prospectively with the FIM. Diagnosis was determined by neuroimaging. Data were
      collected continuously and stored in the departmental database. For analysis of
      data, the patients were divided by side of lesion (right or left hemisphere),
      main clinical syndrome (presence or absence of neglect or aphasic syndromes in
      those with damage to the right or left hemisphere, respectively), type of lesion
      (ischemic, hemorrhagic, etc), and site of lesion (cortical or subcortical).
      SETTING: Neurological rehabilitation ward. PATIENTS: The study population
      included 151 patients of average age 60.8 years; 60% were men. All were admitted
      an average of 28.9 days after stroke and rehabilitated for 109.3 days. MAIN
      OUTCOME MEASURE: The raw FIM total score was determined at 48 to 72 hours after
      admission and at discharge. FIM gain was calculated by subtracting the FIM
      discharge score from the FIM admission score for each individual. Length of stay
      was also recorded. RESULTS: There was no difference in average total FIM scores
      when patients were divided by side of damage (right or left hemisphere).
      Significant findings were obtained for the various parameters when the clinical
      criterion was applied. Patients with neglect or aphasia syndromes showed
      significantly higher gains despite their lower FIM admission scores, but they had
      a much longer in-hospital stay. CONCLUSION: The raw FIM total score is a simple,
      practical, and efficient measure of function in first-stroke patients on
      admission for rehabilitation, provided an appropriate clinical approach is used
      during data analysis. Results can be used for comparison with similar measures,
      determination of admission and discharge policy, and program evaluation. The
      presence of neglect and aphasic syndromes has a significant effect on the various
      measures. Length of stay in rehabilitation is also of paramount importance in
      stroke patients with special clinical syndromes.

PMID- 9196472
TI  - Impairment-specific dimensions within the Functional Independence Measure.
AB  - OBJECTIVE: The analyses presented in this article were intended to seek more fine
      grained impairment-specific dimensions beyond the motor and cognitive dimensions
      of the Functional Independence Measure (FIMSM). DESIGN: The study used factor
      analysis within 20 categories of impairment to test the hypotheses that FIM items
      can be grouped according to functional areas of the body and that these item
      groupings differ depending on the patient's impairment. PATIENTS: Data from
      93,829 patients discharged in 1992 from 252 free-standing rehabilitation
      hospitals and units were obtained from the Uniform Data System for Medical
      Rehabilitation. RESULTS: In 18 of 20 impairment categories, factor analyses of
      patients admission FIM scores showed impairment-specific FIM dimensions. Four
      impairments had a 3-dimensional factor structure, and 14 had a 4-dimensional
      structure. The impairment-specific dimensions were always nested within the motor
      FIM subscale. Reliability coefficients for subscales based on these dimensions
      ranged from .74 to .97. The subscales appear to cluster FIM items by the area of
      body involved, neurological level, or relative energy consumption. CONCLUSION:
      The FIM can be viewed as a multilayered multidimensional measure of human
      function. The impairment-specific dimensions, at an intermediate layer, provide
      insight about the causal linkage between the impairment and resultant patterns of
      disability. Impairment-specific subscales are relevant to those clinical or
      research applications where the type of disability needs to be more closely
      related to impairment.

PMID- 9196474
TI  - Adjustment after spinal cord injury: a 9-year longitudinal study.
AB  - OBJECTIVE: To generate longitudinal data on the stability of life adjustment over
      a 9-year period among a sample of participants with spinal cord injury (SCI).
      DESIGN: A field study was conducted by surveying the adjustment of a sample of
      participants with SCI in 1985 and again in 1994. SETTING: Outpatient files of a
      large, university hospital in the Midwest. PARTICIPANTS: All 235 participants had
      traumatic onset SCI, were a minimum of 18 years of age at the time of first
      testing, and were no less than 2 years postinjury. The average age was 46.7 yrs
      at the time of the 1994 study, with an average of 23.4 yrs having passed since
      injury. MAIN OUTCOME MEASURES: The Life Situation Questionnaire (LSO) was the
      outcome measure used. It was developed in 1973 to measure mostly objective
      information on adjustment and quality of life after SCI. It contains 7 scales and
      40 individual items that were of interest in the current study. RESULTS: Declines
      were identified over the 9-year period in several aspects of subjective well
      being, even though there were no declines in overall activity level and some
      limited increases in participation in employment related activities. CONCLUSIONS:
      The results of this study were in contrast to previous longitudinal follow-ups
      that identified positive changes over time in both subjective and objective
      aspects of quality of life. These changes suggest that participants had a less
      optimistic outlook in 1994 than they did in 1985.

PMID- 9196473
TI  - Early predictors of functional independence 2 years after spinal cord injury.
AB  - OBJECTIVE: To determine: (1) how well factors measured at admission to an acute
      care facility predict functional independence measure (FIM) scores, use of
      personal care assistance, and wheelchair ownership 2 years after traumatic spinal
      cord injury (SCI); (2) the extent that factors measured during inpatient stay add
      to these predictions; and (3) if FIM scores differ through use of assistance and
      wheelchair ownership 2 years after SCI. DESIGN: Prospective, longitudinal.
      SETTING: Tertiary care acute, rehabilitation hospitals and home settings.
      PATIENTS: One hundred sixty SCI admissions. MAIN OUTCOME MEASURES: FIM, use of
      personal care assistance (yes/no), and wheelchair ownership
      (manual/electric/none) 2 years after SCI. RESULTS: Year 2 FIM scores were highly
      correlated (> or = .68) to the ASIA admission and discharge light touch, pin
      prick, and motor scores. Admission neurological status and age accounted for 65%
      of year 2 FIM score variance. Adding hospital events and the discharge ASIA motor
      score increased prediction to 76% of the variance. A separate regression model
      using only year 2 neurological scores and age accounted for 73% of the total FIM
      variance. Discriminant function analysis indicated 86% correct classification
      regarding use of personal care assistance and 88% correct classification of
      wheelchair ownership. Using a separate cross-validation sample, overall
      classification accuracy for assistance was 80% and wheelchair ownership 67%. FIM
      scores were significantly lower in assistance users (78 +/- 24) than nonusers
      (120 +/- 8) and were significantly different between wheelchair ownership groups:
      manual (103 +/- 21), electric (61 +/- 15), and none (125 +/- 2). CONCLUSIONS:
      Late disability can be predicted using early impairment measures. The FIM
      prediction from variables measured during the early treatment phase was as good
      as prediction based on concurrent measures.

PMID- 9196475
TI  - Poststroke depression: an examination of the literature.
AB  - OBJECTIVE: To examine literature on poststroke depression (PSD). DATA SOURCES:
      More than 200 articles related to stroke and depression were selected from a
      computer-based search spanning 1985 to 1995. STUDY SELECTION: All relevant
      articles on PSD. Articles in foreign languages, case studies, anecdotal reports,
      book chapters, and reviews were excluded. DATA EXTRACTION: Summary findings were
      independently reviewed by the authors. DATA SYNTHESIS: PSD remains a frequent
      sequela of stroke; its prevalence remains uncertain because of continued
      methodologic problems in defining subject groupings and in utilizing
      psychiatrically normed assessment tools with neurologically impaired individuals,
      and because of the poor specificity/sensitivity of neuroendocrine markers in
      determining a diagnosis. The etiology of PSD appears to be complex and not fully
      understood. Although there has been much research on PSD, this review highlights
      the sparsity of available literature on its treatment. CONCLUSION: The review
      points out the further need for more carefully designed studies of PSD that
      examine both assessment and treatment.

PMID- 9196476
TI  - Acute low back pain secondary to retroperitoneal hemorrhage in an elderly man.
AB  - Acute low back pain is a common complaint heard in the emergency room and in a
      physiatrist's practice. It is important to rule out occult pathology in patients
      with an atypical presentation. In the case presented here, the patient was
      elderly, developed back pain without preceding trauma or lifting, had a history
      of easy bruisability, had a large ecchymosis, and had worsening back pain with
      bedrest. An abdominal aortic aneurysm was ruled out and the patient was
      discovered to have a large retroperitoneal hemorrhage. He was diagnosed with
      acquired hemophilia secondary to factor VIII inhibitors. This has implications
      for physicians who treat patients with acute low back pain. They must be alert to
      potentially life-threatening causes of low back pain.

PMID- 9196477
TI  - Cerebral angioplasty in a patient with vascular dementia.
AB  - A 66-year-old man with a history of previous transient ischemic attacks had
      progressive memory and gait disturbance caused by severe stenoses of both the
      internal carotid arteries and vertebral arteries. The patient underwent
      percutaneous transluminal angioplasty of the vertebral arteries and
      endarterectomy of the internal carotid arteries with satisfactory results. On
      admission, the patient was alert, but disoriented to time and place. He exhibited
      mild motor weakness in both legs. Neuropsychological tests revealed remarkable
      intellectual deterioration and he required maximum support to perform activities
      of daily living. Higher cortical function and the ability to perform activities
      of daily living improved remarkably after the angioplasty. Angioplasty is an
      alternative therapy to reverse functional deficits in patients with
      cerebrovascular hemodynamic compromise.

PMID- 9196478
TI  - Diversion colitis: a cause of abdominal discomfort in spinal cord injury patients
      with colostomy.
AB  - Diversion colitis is thought to result from nutritional deficiencies secondary to
      fecal diversion. Symptoms include hemorrhagic purulent rectal discharge,
      abdominal pain, and tenesmus. 5-Aminosalicylic acid (5-ASA) and N-butyrate enemas
      have been reported to help this condition non-spinal cord injury (SCI) patients.
      We report the case of a 49-year-old C6 ASIA B tetraplegic man who had received
      colostomy because of intractable ileus 10 years earlier. He presented with a 2
      week history of rectal pain and bleeding. Abdominal and rectal examination on
      admission were unremarkable. Colonoscopy showed a partial stricture 70cm
      proximally to the rectum. The colonic mucosa appeared granular and friable with
      evidence of linear ulceration. Histopathologic study was consistent with colitis.
      The patient developed fever, abdominal distention, and extensive retroperitoneal
      air after endoscopy, suggesting colonic perforation. He was treated with daily 5
      ASA suppository and total parenteral nutrition for the presumed diagnosis of
      diversion colitis, and intravenous antibiotics for perforated colon. After 6
      weeks of treatment with 5-ASA, the patient had decreased rectal pain and
      bleeding. This experience suggests that diversion colitis may be a cause of
      abdominal discomfort in SCI patients and that 5-ASA may be used in the management
      of diversion colitis.

PMID- 9196479
TI  - Neurorehabilitation outcome in moyamoya disease.
AB  - Moyamoya is a disease characterized by occlusion of the internal carotid,
      anterior, and middle cerebral arteries with associated rich collateral flow that
      presents a cloudy appearance on angiogram resembling a puff of smoke. The disease
      is most often progressive with associated hemiparesis and cognitive impairment.
      The functional outcome of patients with moyamoya is not well described in the
      literature. We describe four women (ages 25-36) who were transferred to a
      rehabilitation service after an average 17 days (12-26 days) in an acute care
      setting. Initial functional impairment was estimated using the Functional
      Independence Measure (FIM) score after discharge from inpatient rehabilitation
      (23-53 days) and was compared to the Uniform Data System for Medical
      Rehabilitation (UDSMR) for "first stroke" patients. Average admission FIM scores
      were similar in the two groups. The patients with moyamoya had a higher discharge
      FIM, longer length of stay, and slower rate of progress. Data on long-term
      survival and functional level would be useful, but it appears patients with
      moyamoya disease may benefit from rehabilitation oriented toward neurological
      deficits.

PMID- 9196480
TI  - Trigger point injections.

PMID- 9196481
TI  - Alternative medicine: an expanding health industry.

PMID- 9196482
TI  - Sydney 2000: guarding against disasters.

PMID- 9196483
TI  - The taxanes: miracles for breast cancer treatment or just more chemotherapy?

PMID- 9196484
TI  - Australian multicentre phase II trial of paclitaxel in women with metastatic
      breast cancer and prior chemotherapy.
AB  - OBJECTIVE: To determine the efficacy and safety of paclitaxel given as a three
      hour infusion in patients with metastatic breast cancer which had progressed
      despite hormonal therapy and/or chemotherapy. DESIGN AND SETTING: Multicentre
      phase it trial undertaken in five major centres or hospitals in Sydney, Melbourne
      and Adelaide. PATIENTS AND METHODS: 50 patients with clinically or radiologically
      measurable or evaluable metastatic breast cancer recruited between March and July
      1993. All had received prior chemotherapy, with subsequent disease progression.
      INTERVENTION: Paclitaxel (Anzatax, Faulding) was given at a dose of 175 mg/m2
      intravenously over three hours every three weeks for up to nine courses. MAIN
      OUTCOME MEASURES: Response rate (partial or complete); duration of progression
      free survival; duration of survival; and adverse reactions. RESULTS: Patients had
      a median age of 51 years; 62% had received at least two prior drug regimens for
      metastatic breast cancer and 48% had anthracycline-resistant tumours. A median of
      six paclitaxel courses was given per patient. Overall response rate was 18% (95%
      confidence interval [95% CI], 9%-31%), with complete responses in four patients
      (8%). In patients with anthracycline-resistant tumours, response rate was 25%
      (95% CI, 10%-47%). Response was not influenced by extent of prior treatment.
      Estimated median progression-free survival was 4.1 months (95% CI, 3.2-6.0
      months) and estimated median survival was 6.3 months (95% CI, 6.2-10.3 months).
      Treatment was well tolerated, with neutropenia the major toxic effect.
      CONCLUSIONS: Paclitaxel (three-hour infusion) has significant activity in heavily
      pretreated patients with metastatic breast cancer, including anthracycline
      resistant tumours.

PMID- 9196485
TI  - Relationship of peak expiratory flow rate with mortality and ischaemic heart
      disease in elderly Australians.
AB  - OBJECTIVE: To evaluate the relationships of mortality and ischaemic heart disease
      (IHD) with peak expiratory flow rate (PEF) in the elderly. DESIGN: Prospective
      study with median follow-up of 83 months. SETTING: Dubbo, a New South Wales
      country town (population, 30500). SUBJECTS: Non-institutionalised residents born
      before 1930 (i.e., aged 60 years and over at study entry). Participation rate was
      73% (1235 men and 1570 women). MAIN OUTCOME MEASURES: Baseline demographic,
      psychosocial and standard cardiovascular risk factors, including PEF; all-causes
      mortality, IHD mortality and IHD events (hospitalisations with any manifestation
      of IHD) by tertile of PEF. RESULTS: More subjects with PEF in the lowest tertile
      (I) had a past history of respiratory disease, were current cigarette smokers and
      were taking antihypertensive drugs. During follow-up, 321 men (26%) and 252 women
      (16%) died. All-causes mortality was three (men) to four (women) times higher for
      those in PEF tertile I than for those in tertile III. IHD mortality and IHD
      events showed similar trends. In a proportional hazards model adjusted for age,
      height, smoking status and other risk factors or confounders, the hazard ratios
      (95% confidence interval) for men in PEF tertile I versus tertile III were: all
      causes mortality, 1.62 (1.14-2.30); IHD mortality, 1.75 (0.96-3.20); and IHD
      events, 1.12 (0.82-1.53). For women, respective hazard ratios were 1.92 (1.23
      3.00), 2.58 (1.24-5.39), and 1.16 (0.83-1.63). CONCLUSIONS: We confirm an
      independent, inverse relationship between PEF and all-causes and IHD mortality.
      The data suggest a potential benefit for coronary risk factor management in
      subjects with existing airways disease and further support the case for
      antismoking programs.

PMID- 9196487
TI  - Safety issues in herbal medicine: implications for the health professions.
AB  - The use of herbal medicines in Australia is widespread. A number of factors make
      assessment of adverse effects associated with these products more complex than
      for pharmaceuticals. Problems have resulted from contamination with heavy metals
      and adulteration with prescription drugs in overseas herbal products. A
      classification is proposed for adverse effects associated with herbal medicines,
      and medical practitioners are encouraged to include use of these preparations in
      a patient's drug history and in reports of suspected adverse drug reactions. It
      may be necessary to develop a separate database to promote adverse drug reaction
      reporting for herbal medicine and the wider field of complementary and
      alternative medicine.

PMID- 9196486
TI  - Detection of antibodies to Bartonella henselae in clinically diagnosed cat
      scratch disease.
AB  - OBJECTIVE: To determine the usefulness of an indirect immunoflourescence antibody
      test for antibodies to Bartonella henselae in diagnosing cat scratch disease
      (CSD). DESIGN AND SETTING: Retrospective case survey of 354 patients whose sera
      were tested for antibodies to B. henselae at Royal Perth Hospital, Perth, and the
      Institute of Clinical Pathology and Medical Research, Sydney. In 1994; and
      measurement of the background prevalence of antibodies to B. henselae. MAIN
      OUTCOME MEASURES: Prevalence of antibodies to B. henselae, odds of a positive
      titre (> or = 64) in patients with and without specific risk factors for CSD and
      clinical features of the disease; prevalence of antibodies to B. henselae in
      randomly selected blood donors. RESULTS: Demographic, clinical and cat contact
      data were available for 303 patients. Sixty-four (21.1%) had a positive titre, as
      did 53 of 98 (54%) patients with a history of cat contact and lymphadenopathy.
      This proportion increased to 62% (38 of 61 patients) in patients with a history
      of cat scratch or bite and to 90.3% (28 of 31) in those with cat contact,
      lymphadenopathy and histological evidence of granulomatous lymphadenitis.
      Patients who developed lymphadenopathy after cat contact were significantly more
      likely to have a positive titre than those without this history (odds ratio [OR],
      20.8; 95% confidence interval [95% Cl], 9.6-46; P < 0.0001). Inclusion of a
      history of a cat scratch or bite significantly raised the odds of being
      seropositive (OR, 13.7; 95% Cl, 6.8-28.1; P < 0.0001), and the presence of
      granulomas on lymph node biopsy further increased the odds (OR, 124.4; 95% Cl,
      19.4-1073; P < 0.0001). The prevalence of antibodies to B. henselae in random
      blood donors in New South Wales was about 5% (five of 102 sera samples).
      CONCLUSIONS: The immunofluorescence antibody test for B. henselae can be expected
      to be positive in just over half the patients with clinically suspected CSD, and
      it has a positive predictive value of 83%. In a significant number of cases the
      diagnosis cannot be made on the basis of the results of immunofluorescence
      antibody testing alone and further investigations, including lymph node biopsy,
      may be required.

PMID- 9196488
TI  - The St Marys fragmentation grenade explosion.
AB  - The accidental explosion of a fragmentation grenade in a munitions factory at St
      Marys injured four workers, two critically. The prompt response by ambulances and
      physician-staffed helicopter emergency medical service prevented deaths, but the
      incident suggests lessons for the future handling of urban explosions.

PMID- 9196489
TI  - Management of haematemesis and melaena.
AB  - Upper gastrointestinal bleeding remains a common medical emergency with high
      morbidity and mortality. High risk patients are best managed in specialised
      units. Endoscopy is the procedure of choice for diagnosis and haemostatic therapy
      of peptic ulcers, reducing deaths and the probability of rebleeding, as well as
      the need for surgery; for acute variceal bleeding, pharmacotherapy followed by
      endoscopic ligation is recommended.

PMID- 9196490
TI  - Chest imaging: indications and interpretation.

PMID- 9196491
TI  - Treatment decision-making at the end of life: a survey of Australian doctors'
      attitudes towards patients' wishes and euthanasia.

PMID- 9196492
TI  - Treatment decision-making at the end of life: a survey of Australian doctors'
      attitudes towards patients' wishes and euthanasia.

PMID- 9196493
TI  - The euthanasia debate.

PMID- 9196494
TI  - Universal precautions: attitudes of Australian and New Zealand.

PMID- 9196495
TI  - Universal precautions: attitudes of Australian and New Zealand anaesthetists.

PMID- 9196496
TI  - A case of refractory schistosomiasis.

PMID- 9196497
TI  - A case of refractory schistosomiasis.

PMID- 9196498
TI  - Intravenous glucocorticoids in adult acute severe asthma.

PMID- 9196499
TI  - Dependent opioid users assessed for methadone treatment in Otago: patterns of
      drug use.
AB  - AIMS: To provide detailed information about the types of drugs used and the
      patterns of drug use for injecting drug users presenting for methadone treatment.
      METHODS: A retrospective case note review was carried out for 126 consecutive
      clients who were assessed for methadone treatment in the Otago province over a 2
      year period. Patterns of drug use in the three months prior to presentation were
      recorded. RESULTS: Over 60% of those presenting were using three or more opioid
      drugs, with the most common being homebake (63%), sustained release morphine
      sulphate tablets (62%), buprenorphine (52%), opium poppies (50%) and methadone
      (41%). Use of diacetylmorphine (heroin) was reported primarily by those returning
      from recent overseas travel. Most clients reported the regular use of multiple
      other of clients using benzodiazepines daily. Almost 80% of the group were
      regular tobacco smokers and 11% showed evidence of alcohol disorders (abuse or
      dependence). Low levels of use were reported for cocaine, amphetamines, and
      hallucinogens. CONCLUSION: These patterns of drug use have important implications
      for the planning of methadone treatment programmes.

PMID- 9196500
TI  - Vertical transmission of hepatitis C virus in New Zealand.
AB  - AIMS: To investigate the transmission of hepatitis C virus from viraemic mothers
      to infants. METHODS: The study group comprised 54 hepatitis C ribonucleic acid
      (RNA) positive, human immunodeficiency virus (HIV) negative women attending
      antenatal clinic, their infants when born, 12 previous children and 44 children
      of 29 additional nonpregnant, viraemic women. During the study period there were
      60 live births (1 set of twins, 5 sequential pregnancies). All infants were
      tested at birth for hepatitis C virus (HCV) RNA. Thirty infants were retested at
      6 months or later. Breast milk from 30 mothers was tested for HCV RNA. The 56
      other children were tested for antibody to HCV and HCV RNA. RESULTS: Of the 60
      infants tested at birth, 30 failed to attend a 6 month or later followup, 2
      infants were HCV viraemic by six months of age, 2 infants had one episode of
      possible HCV RNA positivity followed by loss of detectable HCV RNA and 26 have
      shown no evidence of HCV infection. Five of the 30 breast milk samples tested
      were positive for HCV RNA. Four older children of viraemic mothers were HCV RNA
      positive. CONCLUSIONS: In this study, 2 of 30 (6.6%) of infants born to HIV
      negative, HCV viraemic mothers acquired HCV infection. Breast milk remains a
      possible contributory source of infant HCV infection. Management of babies born
      to HCV viraemic mothers should include retesting of baby for HCV RNA at 3 to 6
      months of age.

PMID- 9196501
TI  - Neurotoxicity associated with acyclovir in end stage renal failure.
AB  - AIMS: To alert practitioners to the danger of acyclovir neurotoxicity occurring
      in the presence of renal failure. METHODS: Two case reports of acyclovir
      neurotoxicity in the patients on continuous ambulatory peritoneal dialysis.
      RESULTS: In one case neurotoxicity resulted from the use of a dosage regimen that
      would be appropriate in patients with normal renal function. In the other case,
      neurotoxicity occurred even though a reduced dose of acyclovir was given.
      Supportive management resulted in a complete recovery. CONCLUSIONS: In patients
      with end stage renal failure with varicella zoster infections, when acyclovir is
      prescribed the loading dose should be 400 mg and the maintenance dose should be
      200 mg twice daily.

PMID- 9196502
TI  - The Nova-T 200 intrauterine contraceptive device: a 12 year study.
AB  - AIM: To evaluate the long term clinical performance of the Schering Nova-T 200
      intrauterine contraceptive device. METHOD: From 1982 to 1990, 446 women were
      fitted with their first Nova-T IUD's and followed up until December 1994. By this
      cut off data, 21 (4.7%) were lost to follow up. These were excluded to simplify
      analysis. RESULTS: Of the remaining 425 women, there were 383 multipara and 42
      nullipara. Thirty one percent were fitted with a new Nova-T after 4 years of use.
      The method was uncomplicated in 70% of multiparous women, but in nulliparous
      users, the removal rate for unacceptable bleeding and/or pain was found to be 40%
      compared to 19% for the multipara. An expulsion rate of 4.9% was recorded. The
      overall cumulative accidental pregnancy rate was 3.5% with a Pearl Index of 1.2
      per hundred woman years, a lower rate in older users being the only age related
      event in the study. Possible pelvic inflammatory disease was recorded in 2.8%
      with a Pearl index of 0.96. There was no evidence of subfertility after removal
      in any of the 53 women where a pregnancy was desired. CONCLUSION: The Nova-T 200
      IUCD is safe and cost effective and should continue to be offered as a
      contraceptive option for properly selected women. Although poorly tolerated by
      nullipara, it proved to be very satisfactory for multiparous women, particularly
      nursing mothers and those over 40 years of age.

PMID- 9196503
TI  - The epidemiology of nontuberculous mycobacterial lymphadenitis affecting New
      Zealand children 1986-95.
AB  - AIMS: To study the epidemiological trends of nontuberculous mycobacterial
      lymphadenitis affecting New Zealand children from 1986-95. METHODS: Cases were
      identified from the records of the three regional reference laboratories in New
      Zealand. All children of less than 16 years with a positive culture of
      nontuberculous mycobacteria from a lymph node tissue sample were included.
      RESULTS: One hundred and sixty eight cases were identified, 43 in the first 5
      years (no data available from Waikato) and 125 in the second 5 years of the study
      period. One hundred and fifty three (91%) of cases were in the 0-5 year age group
      and 101 (60%) were female. The head and neck was the most common site of
      infection accounting for 141 (84%) of all infection. In 161 (96%) of cases the
      causative organism was Mycobacterium avium intracellulare complex. CONCLUSION:
      Nontuberculous mycobacterial infections cause a subacute lymphadenitis in
      preschool children, usually affecting the lymph nodes of the head and neck. The
      annual number of microbiologically confirmed cases in New Zealand had increased
      substantially over recent years, most notably since 1992. The reason for the
      increase is unknown but possible explanations include increased awareness of
      mycobacterial disease, external factors causing either changes in the
      distribution or virulence of mycobacteria in the environment and alterations in
      the human immune response.

PMID- 9196505
TI  - Insulin for overseas.

PMID- 9196504
TI  - Intervention in alcohol use disorder in a general practice.
AB  - AIM: To report the outcome of intervention in 70 patients with alcohol use
      disorder in a general practice. METHOD: Of the 84 patients age 18-69 years
      identified clinically or by a screening programme with alcohol use disorder, 70
      who were available for at least 2 year follow up after diagnosis were included in
      the study group. The clinical notes of these patients were reviewed to determine
      evidence of sustained achievement of abstinence or controlled drinking and
      factors contributing to successful change in alcohol use. RESULTS: Sustained
      abstinence or controlled drinking was verified for 31 patients (44%) with a
      further 26 patients (37%) reporting reduction in alcohol use without evidence of
      sustained improvement. The mean interval from diagnosis to sustained improvement
      was 4 years. Only five patients accepted referral to specialist alcohol units.
      Successful change in the 31 patients achieving their drinking goal was directly
      related to intervention at the surgery for 9 patients. CONCLUSION: A motivational
      approach with focus on the patient's perception of the issues proved relatively
      successful in this practice. A prolonged period of change was required to achieve
      drinking goals. Other factors contributing to improvement are discussed.

PMID- 9196506
TI  - Needle exchange service.

PMID- 9196507
TI  - Cannabis uses in young New Zealanders.

PMID- 9196508
TI  - Video-assisted thoracoscopic surgery (VATS) in the management of spontaneous
      pneumothorax.

PMID- 9196509
TI  - Predicting survival in cystic fibrosis.

PMID- 9196510
TI  - Airway wall remodelling in asthma.

PMID- 9196511
TI  - A prognostic model for the prediction of survival in cystic fibrosis.
AB  - BACKGROUND: The treatment for endstage cystic fibrosis is, where appropriate,
      double-lung, heart-lung or, occasionally, heart-lung-liver transplantation.
      Optimising the timing of transplantation depends upon an accurate prediction of
      survival, but while current criteria give some guidance to this, they are not
      based upon statistically derived prognostic models. METHODS: Data collected
      prospectively on 403 patients with cystic fibrosis, recruited between 1969 and
      1987 (cohort A), were analysed by log rank and univariate Cox regression analysis
      to determine variables that accurately predict survival. The significant
      variables were then subject to time dependent multivariate Cox regression
      analysis to generate a prognostic model. The model was validated, within the
      study population, using split sample testing, and was subsequently validated in a
      further cohort of patients recruited since October 1988 (cohort B). RESULTS: One
      hundred and eighty eight (50.4%) of the study cohort died within the study
      period. Percentage predicted forced expiratory volume in one second (FEV1),
      percentage predicted forced vital capacity (FVC), short stature, high white cell
      count (WBC), and chronic liver disease (as evidenced by the presence of
      hepatomegaly) were negatively correlated with survival. These variables, when
      combined into a prognostic index, accurately predicted one year survival in the
      study population and in the cohort recruited since 1988. CONCLUSION: This
      prognostic index may prove valuable in predicting prognosis in other cohorts with
      cystic fibrosis and thereby improve the timing of transplantation.

PMID- 9196512
TI  - Epidemiology of chronic Pseudomonas aeruginosa infections in the airways of lung
      transplant recipients with cystic fibrosis.
AB  - BACKGROUND: The source of airway colonisation with Pseudomonas aeruginosa is not
      well defined in patients with cystic fibrosis after lung transplantation. Using a
      DNA-based typing system a study was undertaken to investigate whether lung
      transplant recipients acquired new strains of P aeruginosa or retained those they
      had before transplantation. METHODS: Seventy four P aeruginosa isolates taken
      before and after transplantation were analysed from 11 patients with cystic
      fibrosis who had undergone lung transplantation in the Medical School of Hannover
      between 1988 and 1994. The genetic relatedness of the 74 P aeruginosa strains was
      evaluated from macrorestriction fragment pattern similarity. RESULTS: Each of the
      11 lung transplant recipients harboured one identical P aeruginosa clone before
      and after transplantation. The airways of four of the 11 patients were
      preoperatively colonised by two or three different clones, but six months after
      transplantation only one clone was detectable. CONCLUSIONS: These results show
      that there is no change in the P aeruginosa population in the airways of lung
      transplant recipients before and after transplantation and it is assumed that the
      chronic drainage of P aeruginosa into the lung allografts is caused by the
      bacterial reservoir in the paranasal sinuses and the trachea.

PMID- 9196513
TI  - Immunopathological changes in the airways of stable lung transplant recipients.
AB  - BACKGROUND: Pathological obliterative bronchiolitis, characterised by
      inflammation and occlusion of airways, is a serious complication of lung
      transplantation. Endobronchial biopsy (EBB) provides a means of examining
      transplanted airways. This study aimed to investigate the role of EBB samples in
      revealing early signals of airway injury. METHODS: In 18 stable lung transplant
      recipients with close to maximal lung function (median FEV1, best after
      transplantation 100%, interquartile range 98-100%) EBB samples were taken
      simultaneously with transbronchial biopsy samples and bronchoalveolar lavage
      (BAL) fluid (median 195 days after transplantation). OCT embedded specimens were
      snap frozen on an isopentane slurry made with liquid nitrogen and 7 microns
      sections were stained with monoclonal antibodies using a three stage
      immunoperoxidase method. RESULTS: Compared with nine non-transplanted control
      subjects, EBB specimens from the stable transplant group had significantly
      increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p =
      0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median
      84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115).
      There was an increase in CD68 positive cells in the EBB specimens from transplant
      recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for
      the difference 1 to 84). CD3, CD4, and CD25 counts were similar in the two
      groups. EBB findings were not influenced by age, sex, indication for transplant,
      immunosuppression doses or levels, nor the presence of airway commensals in the
      BAL fluid. CONCLUSIONS: EBB is practicable in a transplant setting and provides
      information about bronchial inflammatory changes. It is likely that there is
      ongoing inflammation, possibly rejection mediated, even in healthy lung
      transplant recipients despite triple immunosuppression.

PMID- 9196514
TI  - Treatment of complicated spontaneous pneumothorax by simple talc pleurodesis
      under thoracoscopy and local anaesthesia.
AB  - BACKGROUND: Complicated (recurring or persistent) spontaneous pneumothorax
      requires treatment either by talc pleurodesis with bullae electrocoagulation or,
      more aggressively, by thoracotomy or video-assisted thoracoscopic surgery.
      However, the relative merits of bullectomy, pleurectomy, and pleurodesis have not
      yet been established in the treatment of spontaneous pneumothorax. METHODS: The
      complications, duration of drainage, length of hospital stay, and immediate and
      long term success rate of treating complicated spontaneous pneumothorax with talc
      pleurodesis under local anaesthesia supplemented with nitrous oxide were studied.
      RESULTS: Talc pleurodesis was performed in 93 patients without serious
      complication (two benign arrhythmias, two subcutaneous emphysema, two pneumonia,
      one bronchospasm). The procedure was immediately successful in 90 patients (97%)
      with a median duration of drainage of five days (range 2-40) and a median length
      of hospital stay of 5.2 days (range 3-40). After a mean follow up duration of 5.1
      (range 1-9.4) years in 84 cases the long term success rate was 95%, although six
      cases developed a small localised recurrence of spontaneous pneumothorax which
      did not require further surgery. Macroscopic staging at thoracoscopy was only
      carried out in the last 59 cases of whom 10 (17%) had bullae with a diameter of >
      2 cm. In this group of patients the risk of definitive failure requiring surgery
      was significantly higher than in those patients without such bullae (odds ratio
      7; confidence interval 3.7 to 13.3; p = 0.03), although eight of these patients
      did not require thoracotomy. Total lung capacity was reduced immediately after
      talc pleurodesis (mean (SD) 75 (23)% predicted at 10 days) but had improved to 95
      (14)% predicted at 12 months. CONCLUSIONS: This study shows that simple
      thoracoscopic talc pleurodesis under local anaesthesia is a safe and effective
      treatment for complicated spontaneous pneumothorax. However, patients with bullae
      of > 2 cm in diameter have a greater risk of treatment failure.

PMID- 9196515
TI  - Serial computed tomographic evaluation in desquamative interstitial pneumonia.
AB  - BACKGROUND: Desquamative interstitial pneumonia (DIP) may represent the early
      stage and usual interstitial pneumonia (UIP) the late stage of the same disease.
      The purpose of this study was to evaluate the computed tomographic (CT) features
      of DIP, to evaluate the changes in pattern and extent of disease over time, and
      to determine whether the appearances of DIP on the CT scan change to those of UIP
      during follow up. METHODS: Sequential CT evaluation was conducted on eight
      patients with DIP over a mean (SD) follow up period of 3.2 (1.3) years (range 1.6
      6.5). The relative extents of ground glass and honeycombing were determined from
      serial CT scans. Changes in the extent and appearance of the disease were
      examined in paired anatomically comparable CT sections. RESULTS: Common features
      on the CT scans of patients with DIP were a homogeneous increase in lung
      attenuation (n = 5), linear areas of attenuation (n = 5), relatively well
      preserved lung architecture (n = 5), and the presence of small cysts (n = 6).
      Uncommon features were architectural distortion (n = 3), and traction
      bronchiectasis (n = 1). In six patients with DIP with cystic spaces these did not
      change with time in three cases, in two they regreased, and in one patient they
      increased. Open lung biopsy samples from patients with DIP with many cystic
      lesions showed dilated alveolar ducts and bronchioles and/or pulmonary cysts, as
      well as numerous macrophage-filled air spaces and mild fibrosis, but no typical
      honeycomb cysts were seen. CONCLUSIONS: Some of the microcysts in DIP are
      different from the honeycomb cysts seen in UIP, and some of the cysts seen in
      patients with DIP resolve with time. DIP does not progress to UIP in the short
      term.

PMID- 9196516
TI  - Metabolism in patients with small cell lung carcinoma compared with patients with
      non-small cell lung carcinoma and healthy controls.
AB  - BACKGROUND: Weight loss is a frequently occurring problem in patients with lung
      cancer due to an increased resting energy expenditure (REE) and a decreased
      energy intake. The aim of the present study was to compare the metabolic and
      inflammatory characteristics of patients with small cell lung carcinoma (SCLC)
      and non-small cell lung carcinoma (NSCLC). The metabolic parameters of the lung
      cancer population were compared with those of a healthy control group. METHODS:
      REE was measured in 66 patients with lung cancer, subdivided according to their
      histology, and in 33 healthy controls matched for sex, age, and fat free mass
      (FFM). Inflammatory mediators were measured in the plasma of the patients with
      lung cancer. RESULTS: An increased REE adjusted for FFM was found in the patients
      with lung cancer. Those with small cell lung carcinoma (SCLC) had an increased
      REE adjusted for FFM (mean 1925 kcal/day) compared with those with non-small cell
      lung carcinoma (NSCLC) (mean 1789 kcal/day, 95% CI for difference 36 to 236). FFM
      accounted for 69% and 48% of the inter-individual variation in REE in controls
      and those with NSCLC, respectively, while FFM accounted for only 25% of the
      variation in REE in patients with SCLC in whom the fat mass (FM) also contributed
      significantly (28%) to the variation in REE. Increased concentrations of soluble
      TNF-receptor 75 (sTNF-R75) and cortisol were found in patients with SCLC compared
      with those with NSCLC. Lipopolyasccharide binding protein (LBP) and sTNF-R55 were
      related to plasma levels of cortisol. CONCLUSION: An enhanced REE adjusted for
      FFM occurred in patients with SCLC compared with those with NSCLC.

PMID- 9196517
TI  - Inhibition of allergen-induced airway obstruction and leukotriene generation in
      atopic asthmatic subjects by the leukotriene biosynthesis inhibitor BAYx 1005.
AB  - BACKGROUND: Leukotriene receptor antagonists significantly blunt allergen-induced
      bronchoconstriction in asthmatic subjects. Inhibitors of leukotriene synthesis
      should theoretically provide similar protection, but conflicting results have
      been obtained when synthesis inhibitors have been tested in allergen challenge.
      BAYx 1005, a new inhibitor of leukotriene synthesis, was therefore evaluated in
      an allergen bronchoprovocation study. METHODS: Ten men with mild allergic asthma
      and bronchial hyperresponsiveness to histamine were recruited. On two different
      occasions each subject inhaled a single dose of allergen, previously determined
      to cause at least a 20% fall in forced expiratory volume in one second (FEV1)
      four hours after ingestion of 750 mg BAYx 1005 or placebo in a double blind
      crossover design. Urinary excretion of leukotriene E4 was measured before and
      during the challenges. RESULTS: The mean (SE) maximal fall in FEV1 was 7.1 (1.7)%
      after BAYx 1005 and 21.0 (3.0)% after placebo (p < 0.001). The mean difference
      between treatments was 13.9 (95% CI 7.0 to 20.8) for the maximal fall in FEV1.
      All subjects were protected by BAYx 1005, the mean inhibition of the fall in FEV1
      being 70.0 (7.0)%. The mean area under the curve (AUC) for urinary excretion of
      leukotriene E4 in the first two hours after the challenge was 1.7 (0.9) after
      placebo and 0.4 (0.6) after BAYx 1005 (difference = 1.3 (95% CI-0.1 to 2.7); p <
      0.05). CONCLUSIONS: These results indicate that BAYx 1005 is a potent inhibitor
      of allergen-provoked leukotriene synthesis in asthmatic subjects and lend further
      support to the suggestion that leukotrienes are important mediators of allergen
      induced bronchoconstriction.

PMID- 9196518
TI  - Attenuation of early and late phase allergen-induced bronchoconstriction in
      asthmatic subjects by a 5-lipoxygenase activating protein antagonist, BAYx 1005.
AB  - BACKGROUND: The cysteinyl leukotrienes (LTC4, LTD4 and LTE4) have been implicated
      in the pathogenesis of allergen-induced airway responses. The effects of
      pretreatment with BAYx 1005, an inhibitor of leukotriene biosynthesis via
      antagonism of 5-lipoxygenase activating protein, on allergen-induced early and
      late asthmatic responses has been evaluated. METHODS: Eight atopic subjects with
      mild asthma participated in a two period, double blind, placebo controlled, cross
      over trial. Subjects were selected on the basis of a forced expiratory volume in
      one second (FEV1) of > 70% predicted, a methacholine provocative concentration
      causing a 20% fall in FEV1 (PC20) of < 32 mg/ ml, a documented allergen-induced
      early response (EAR, > 15% fall in FEV1 0-1 hour after allergen inhalation) and
      late response (LAR, > 15% fall in FEV1 3-7 hours after allergen inhalation), and
      allergen-induced airway hyperresponsiveness (at least a doubling dose reduction
      in the methacholine PC20 30 hours after allergen inhalation). During the
      treatment periods subjects received BAYx 1005 (500 mg twice daily) or placebo for
      3.5 days; treatment periods were separated by at least two weeks. On the third
      day of treatment, two hours after administration of medication, subjects
      performed an allergen inhalation challenge and FEV1 was measured for seven hours.
      RESULTS: Treatment with BAYx 1005 attenuated the magnitude of both the allergen
      induced early and late asthmatic responses. The mean (SE) maximal fall in FEV1
      during the EAR was 26.6 (3.3)% during placebo treatment and 11.4 (3.3)% during
      treatment with BAYx 1005 (mean difference 15.2 (95% confidence interval (CI) 9.4
      to 21.00) with a mean protection afforded by BAYx 1005 of 57.1%. The mean (SE)
      maximal fall in FEV1 during the LAR was 19.8 (5.7)% during placebo treatment and
      10.7 (4.4)% during BAYx 1005 treatment (mean difference 9.2 (95% CI 1.4 to 17.0)
      with a mean protection afforded by BAYx 1005 of 46.0%. The area under the time
      response curve (AUC0-3) was also reduced after treatment with BAYx 1005 compared
      with placebo by 86.5%.h (mean difference 26.3 (95% CI 17.1 to 38.5)) and the AUC3
      7 by 59.6%.h (mean difference 26.9 (95% CI-3.8 to 57.6)). CONCLUSIONS: These
      results show that antagonism of 5-lipoxygenase activating protein can attenuate
      allergen-induced bronchoconstrictor responses and support an important role for
      the cysteinyl leukotrienes in mediating these asthmatic responses.

PMID- 9196520
TI  - A short-term controlled trial of an adjustable oral appliance for the treatment
      of mild to moderate obstructive sleep apnoea.
AB  - BACKGROUND: Although oral appliances are effective in some patients with
      obstructive sleep apnoea (OSA), they are not universally effective. A novel
      anterior mandibular positioner (AMP) has been developed with an adjustable hinge
      that allows progressive advancement of the mandible. The objective of this
      prospective crossover study was to compare efficacy, side effects, patient
      compliance, and preference between AMP and nasal continuous positive airway
      pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS:
      Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a
      mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7
      (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in
      and a two week wash-out period and two treatment periods (AMP and nCPAP) each of
      four months. Efficacy, side effects, compliance, and preference were evaluated by
      a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early
      in the study and three refused to cross over so treatment results are presented
      on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with
      nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p < 0.01). Eleven
      of the 20 patients (55%) who used the AMP were treatment successes (reduction of
      AHI to < 10/hour and relief of symptoms), one (5%) was a compliance failure
      (unable or unwilling to use the treatment), and eight (40%) were treatment
      failures (failure to reduce AHI to < 10/hour and/or failure to relieve symptoms).
      Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six
      (30%) were compliance failures, and there were no treatment failures. There was
      greater patient satisfaction with the AMP (p < 0.01) than with nCPAP but no
      difference in reported side effects or compliance. CONCLUSIONS: AMP is an
      effective treatment in some patients with mild to moderate OSA and is associated
      with greater patient satisfaction than nCPAP.

PMID- 9196519
TI  - Abdominal muscle recruitment and PEEPi during bronchoconstriction in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: It has been recently shown that, when breathing at rest, many
      patients with severe chronic obstructive pulmonary disease (COPD) contract
      abdominal muscles during expiration, and that this contraction is an important
      determinant of positive end expiratory alveolar pressure (PEEPi). In this study
      the effects of acute bronchoconstriction on abdominal muscle recruitment in
      patients with severe COPD were studied, together with the consequence of
      abdominal muscle action on chest wall mechanics. METHODS: Breathing pattern,
      pleural (PPL) and gastric (PGA) pressures, and changes in abdomen anteroposterior
      (AP) diameter were studied in 14 patients with COPD (mean forced expiratory
      volume in one second (FEV1) 1.06 (0.08) 1) under control conditions and during
      histamine-induced bronchoconstriction. RESULTS: The analysis of plots of PGA
      versus the AP diameter of the abdomen revealed that during maximal broncho
      constriction (decrease in FEV1 of 34.8% (95% confidence intervals (CI) 29.9 to
      39.7)) the expiratory rise in PGA increased significantly whereas end expiratory
      abdomen AP diameter decreased, indicating marked abdominal muscle recruitment. As
      a consequence, the rib cage compartment accounted for all of the volume of
      hyperinflation during bronchoconstriction (mean value 0.66 I, 95% CI 0.49 to
      0.83). Positive end expiratory alveolar pressure during progressive
      bronchoconstriction was related directly to the expiratory rise in PGA and
      inversely to the expiratory time. CONCLUSIONS: The results indicate that, in
      patients with severe COPD, the abdominal muscles are recruited during acute
      bronchoconstriction. This recruitment probably preserves diaphragm length at the
      beginning of inspiratory muscle contraction despite the hyperinflation, and
      contributes significantly to positive end expiratory alveolar pressure. The
      degree of dynamic pulmonary hyperinflation during bronchoconstriction can be
      overestimated if abdominal muscle contraction is not assessed.

PMID- 9196521
TI  - Nitric oxide and prostacyclin as test agents of vasoreactivity in severe
      precapillary pulmonary hypertension: predictive ability and consequences on
      haemodynamics and gas exchange.
AB  - BACKGROUND: In patients with primary pulmonary hypertension who respond to
      vasodilators acutely, survival can be improved by the long term use of calcium
      channel blockers. However, testing for such a response with calcium channel
      blockers or prostacyclin (PGI2) may cause hypotension and adversely affect gas
      exchange. Nitric oxide (NO), which does not have these effects, could be a better
      test agent. METHODS: NO (10, 20, and 40 ppm for 15 minutes), PGI2 (1-->10
      ng/kg/min), and oral nifedipine (10 mg, then 20 mg/h) were administered
      sequentially to 10 patients after determination of the 24 hour spontaneous
      variability of their pulmonary and systemic mean arterial pressures. Patients
      were considered responders if the mean pulmonary artery pressure or pulmonary
      vascular resistance decreased by 20% or more. RESULTS: Six patients (60%)
      responded to all three agents, and three to none of the agents. One patient
      responded to PGI2 only. In those who responded to vasodilators, NO had no major
      effect on gas exchange or systemic haemodynamics, while PGI2 and nifedipine both
      induced systemic hypotension (mean (SD) systemic arterial pressure 72 (14) versus
      89 (19) mm Hg with PGI2 and 72 (15) versus 86 (17) mm Hg with nifedipine, p <
      0.05) and hypoxaemia (PaO2 8.7 (1.4) versus 10.8 (1.0) kPa with PGI2 and 8.6
      (1.4) versus 10.2 (1.5) kPa with nifedipine, p < 0.05) and increased venous
      admixture (28 (9) versus 14 (4)% with PGI2 and 22 (9) versus 13 (5)% with
      nifedipine, p < 0.05). CONCLUSIONS: NO inhalation can accurately predict a
      vasodilator response to nifedipine in patients with severe pulmonary hypertension
      without adverse effects on systemic haemodynamics and gas exchange. This absence
      of side effects may make it a more appropriate agent for testing the vasodilator
      response.

PMID- 9196522
TI  - Cellular profiles in asthmatic airways: a comparison of induced sputum, bronchial
      washings, and bronchoalveolar lavage fluid.
AB  - BACKGROUND: Analysis of bronchoalveolar lavage fluid has improved our
      understanding of the pathogenesis of asthma. Safety issues and access to expert
      resources limit this techniques as a research tool. Induced sputum is a non
      invasive method of collecting airway fluid which is applicable to subjects with a
      range of severity of airflow obstruction. The method of sputum collection and
      processing differs between groups. A study was undertaken to compare induced
      sputum with bronchoscopically collected fluid. METHODS: Sixteen patients with
      mild stable asthma underwent both sputum induction and bronchoscopic examination
      with bronchial washings and bronchoalveolar lavage (BAL) in random order, with
      each procedure being separated by an interval of 12 days. Airway fluid was
      processed and stained for differential cell counting. RESULTS: Induced sputum was
      relatively rich in neutrophils and eosinophils compared with bronchial washings
      and BAL fluid (mean (SE) 1.3 (0.4)%, 5.0 (2.7)%, and 36.4 (3.7)% neutrophils and
      0.6 (0.1)%, 1.6 (0.6)%, and 3.3 (1.1)% eosinophils in BAL fluid, bronchial
      washings, and induced sputum, respectively). The proportions of cells obtained at
      sputum induction correlated with those in bronchial washings but not BAL fluid (r
      = 0.6 and 0.7 for neutrophils and eosinophils, respectively, p < 0.05). By
      contrast, induced sputum had a lower proportion of lymphocytes and macrophages
      than bronchial washings or BAL fluid, without any correlation. CONCLUSION:
      Induced sputum is rich in neutrophils and eosinophils and poor in lymphocytes,
      suggesting an origin in the larger airways. Induced sputum adequately reflects
      the findings in fluid collected by direct bronchoscopy.

PMID- 9196523
TI  - Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection.
AB  - BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral
      blood of patients infected with Mycobacterium tuberculosis are few and
      contradictory. The percentage of gamma/delta T lymphocytes in the peripheral
      blood of tuberculin positive and tuberculin negative patients with Mycobacterium
      tuberculosis infection and healthy controls was compared. METHODS: Thirty six
      patients infected with Mycobacterium tuberculosis and 11 healthy controls were
      studied. Lymphocytes were separated, cytocentrifuged onto glass microscope
      slides, and reacted with anti-gamma/delta monoclonal antibody. The percentage of
      gamma/delta positive cells was determined by microscopic counting of 300
      lymphocytes. RESULTS: No difference was found in the percentage of gamma/delta T
      lymphocytes between patients and controls. However, when the patients were
      divided into two groups according to reactivity or non-reactivity in the Mantoux
      skin reaction a higher percentage of gamma/delta T lymphocytes was found in the
      peripheral blood of patients with tuberculin anergy than in tuberculin positive
      patients or controls. CONCLUSIONS: Higher gamma/delta T cell counts are found in
      tuberculin negative patients with tuberculosis than in tuberculin positive
      patients or tuberculin positive controls. The high gamma/delta T cell counts in
      tuberculin anergic patients may reflect a shift in the immune response in a Th2
      direction characterised by increased antibody production and decreased cell
      mediated responses.

PMID- 9196524
TI  - Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis.
AB  - BACKGROUND: Pneumonitis is a rare but potentially life threatening side effect of
      methotrexate treatment for rheumatoid arthritis which needs to be distinguished
      from interstitial lung disease due to rheumatoid arthritis. METHODS: To examine
      the value of bronchoalveolar lavage (BAL) in diagnosing methotrexate pneumonitis,
      the BAL cell profile of four patients with methotrexate pneumonitis was compared
      with findings in 16 patients with rheumatoid arthritis treated with methotrexate
      without clinical or radiological evidence of lung disease and eight patients with
      interstitial lung disease secondary to rheumatoid arthritis treated with
      methotrexate. RESULTS: Methotrexate pneumonitis was associated with an increase
      in the lymphocytes in the BAL fluid to 33-68% of total BAL cells. BAL
      lymphocytosis was also found in five patients in each of the two control groups.
      The four patients with methotrexate pneumonitis had a disproportionate increase
      in CD4+ cells to 72-84% of total lymphocytes and in the CD4/CD8 ratio to 17.0,
      6.6, 8.7, and 4.0, respectively, figures which exceeded those of the two control
      groups. CONCLUSIONS: Methotrexate pneumonitis was associated with lymphocytic
      alveolitis with a preferential increase in CD4+ cells. This pattern differs from
      that in interstitial lung disease due to rheumatoid arthritis and may therefore
      assist in making an early diagnosis of methotrexate pneumonitis.

PMID- 9196526
TI  - Respiratory conditions associated with haematological malignancies.

PMID- 9196525
TI  - Mechanisms of virus induced exacerbations of asthma.

PMID- 9196527
TI  - Bronchiectasis in bone marrow transplantation.
AB  - Two patients are described with clinical and radiographic bronchiectasis which
      occurred after allogeneic bone marrow transplantation for haematological
      malignancy. Both had evidence of chronic graft versus host disease in other
      organs. Increased immunosuppression with corticosteroids resulted in clinical
      response, although both patients persisted with chronic mucopurulent sputum
      production and one had progressive airflow obstruction. Bronchiectasis may be an
      under-recognised manifestation of chronic graft versus host disease of the lung.

PMID- 9196528
TI  - Pseudohypoxaemia in a patient with acute leukaemia.
AB  - Patients with acute leukaemia may have spuriously low arterial oxygen tensions
      (PaO2). The markedly increased numbers of white blood cells in these patients
      rapidly consume dissolved plasma oxygen resulting in dramatically decreased PaO2
      and calculated oxygen saturations. The case history is reported of a patient with
      a white blood count of 191 000/mm3 in whom multiple arterial blood gas
      measurements documented hypoxaemia out of proportion to the clinical picture.
      Pulse oximetry was used to confirm higher haemoglobin oxygen saturations and to
      establish the spuriously low plasma oxygen tensions in this patient.

PMID- 9196529
TI  - Malignant chondroid syringoma presenting as multiple pulmonary nodules.
AB  - Malignant chondroid syringoma, a very rare tumour, presenting with multiple
      pulmonary metastases in a 50 year old woman is described. Initial diagnostic
      confusion with pulmonary hamartoma occurred due to histopathological
      similarities. However, re-examination of a skin biopsy specimen taken 17 years
      previously from a hand lesion yielded the necessary information to identify the
      pulmonary lesions definitively as metastases from the original skin lesion. The
      features of this very rare indolent tumour are described.

PMID- 9196530
TI  - Quality of life in adults with cystic fibrosis.

PMID- 9196531
TI  - Necroscopic histology and the cause of death.

PMID- 9196532
TI  - Delays in the diagnosis and treatment of lung cancer.

PMID- 9196533
TI  - Seasonality of tuberculosis.

PMID- 9196534
TI  - Nebulised antipseudomonal antibiotic therapy in cystic fibrosis.

PMID- 9196535
TI  - Pulmonary infiltration after exposure to home renovation dust.

PMID- 9196536
TI  - Occupation and COPD.

PMID- 9196537
TI  - Gianturco stents in the tracheobronchial tree.

PMID- 9196538
TI  - N-methyl-D-aspartate receptors, nitric oxide, and ethanol tolerance.
AB  - Several experimental models have been used to study tolerance to ethanol. The
      development of tolerance to the motor incoordinating effect of a single
      administration of ethanol occurs within 8-24 h after the effect of the first dose
      has disappeared. This form of tolerance is designated rapid tolerance and seems
      to involve functional rather than pharmacokinetic mechanisms. Like chronic
      tolerance, rapid tolerance has been shown to be influenced by processes related
      to learning and memory. It is known that N-methyl-D-aspartate (NMDA) receptor
      systems are involved in the expression and maintenance of one form of long-term
      potentiation (LTP), a synaptic adaptive process which has been suggested to be
      the cellular basis of memory or associative memory. Considering the similarities
      between learning and tolerance, the effects of NMDA agonists and antagonists on
      tolerance to ethanol were investigated. Our studies demonstrated that NMDA
      antagonists that impair learning, such as dizocilpine or ketamine, inhibit
      tolerance, while NMDA agonists that improve learning, such as D-cycloserine,
      increase tolerance. Moreover, the nitric oxide synthase inhibitor L-nitroarginine
      blocks tolerance to the effects of ethanol. Taken together, these data confirm
      the involvement of the NMDA system in ethanol tolerance and emphasize the
      participation of learning in this phenomenon.

PMID- 9196539
TI  - Electrophoretic variation of hair proteins.
AB  - Hair follicle cells secrete a complex assortment of proteins that form the hair
      shaft, and can be classified into two major groups. The low-sulfur proteins are
      keratins that contribute to the backbone of intermediate filaments, and the high
      sulfur proteins are associated with these filaments. In the present investigation
      we describe a comparative electrophoretic study of normal human hair proteins
      from 182 individuals, including some families. Hair proteins were extracted in
      urea buffer (pH 9.3), examined by 10% polyacrylamide gel electrophoresis (pH 8.8)
      in the presence of sodium dodecyl sulfate and stained with Coomassie brilliant
      blue. Eighteen bands appeared and were reproducible in most individuals, with
      apparent molecular mass ranging from 10.0 to approximately 100 kDa. Based on the
      most prominent bands, an electrophoretic profile defined as the "frequent
      profile" was observed. This profile was observed in 180 individuals and consisted
      of 6 prominent bands, 4 of them of apparent molecular mass in the 40-70-kDa
      range, which is characteristic of keratins (61.9 +/- 1.02, 58.5 +/- 1.21, 47.9 +/
      1.58, and 45.4 +/- 1.53 kDa), and 2 bands with lower molecular mass (18.9 +/-
      0.75 and 13.7 +/- 0.91 kDa). In 2 samples from unrelated women, an additional
      band of 42.1 +/- 1.72 kDa appeared. The meaning of this variant is still under
      investigation.

PMID- 9196540
TI  - Evaluation of protein and peptide hydrolases in DOCA-salt hypertensive rat
      treated with chlorthalidone.
AB  - We have reported that chlorthalidone (Chlor) prevents the development of heart
      hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The
      present study was carried out to determine whether Chlor (8 mg/day per animal,
      added to the food, for 20 days) affects kidney and heart hypertrophy in DOCA-salt
      (8 mg/kg, sc, twice a week) rats by causing alterations in protein and peptide
      hydrolysis. Heart (left ventricle) and kidney enzyme activities were measured in
      tissue homogenates from normal-control, salt-control, DOCA-salt and DOCA-salt
      Chlor male Wistar rats (N = 6 for each group), using azocasein as the substrate
      for proteolytic enzymes and specific peptides for prolylendopeptidase (PEP) and
      multicatalytic proteinase (MCP). The tissue weight/body weight ratio increased in
      parallel to elevation of blood pressure. The left ventricular muscle hypertrophy
      (26%, P < 0.05) present in the DOCA-salt hypertensive group was completely
      prevented by simultaneous Chlor treatment. Chlor treatment did not change the
      kidney hypertrophy (+79%, P < 0.;05) observed in the salt-control (+57%, P <
      0.05) and DOCA-salt (+74%, P < 0.05) groups. The hydrolysis of peptides by PEP
      and MCP was similar in the normal and salt-control groups. The heart PEP activity
      was 24% higher (P < 0.01) in DOCA-salt rats, whereas MCP activity was not
      different when compared to control groups. DOCA-salt treatment increased MCP
      activity in the kidney by 44% while PEP activity did not differ from that of
      control groups. The hydrolysis of proteins by heart enzymes was increased by salt
      by 47%. Chlor treatment restored the reduction in protein hydrolysis induced by
      DOCA-salt (a 21% decrease, P < 0.05) to a level similar to that of the normal
      control group. Similarly, Chlor coadministration prevented the 30% reduction in
      renal proteolytic activity elicited by DOCA-salt treatment. Although Chlor
      treatment prevented the DOCA-salt-induced reduction in protein hydrolysis, this
      response did not interfere with kidney hypertrophy. The mechanism by which
      hypertension produces hypertrophy is unclear, but our results suggest that this
      structural modification is not related to the activities of some peptidases, e.g.
      protein and peptide hydrolases.

PMID- 9196541
TI  - Basic aminopeptidase from rabbit kidney: purification and partial
      characterization.
AB  - The aminopeptidase activity of a homogenate of rabbit kidney treated with Triton
      X-100 was measured using L-aminoacyl-2-naphthylamides (AA-NA). After gradient
      elution ion-exchange chromatography, four peaks of aminopeptidase activity were
      eluted. The enzyme eluted at 450 microS containing 33.5% of the activity towards
      Arg-NA was applied to a Superdex 75 column and presented only one protein band on
      10% SDS-polyacrylamide gel electrophoresis. This enzyme has an apparent molecular
      mass of 78 kDa, is five-fold activated by 0.15 M NaCl and the highest Vmax/KM
      ratio was obtained with Arg-NA. Enzyme activity was inhibited 100% by 0.13 mM
      sodium p-hydroxymercuribenzoate, 20% by 0.75 mM EDTA and 100% by 0.66 mM o
      phenanthroline. Puromycin and bestatin behaved like competitive inhibitors with a
      Ki of 0.60 mM and 5.0 microM and 5.0 microM, respectively.

PMID- 9196542
TI  - Isolation and possible composition of glucosylceramides from Paracoccidioides
      brasiliensis.
AB  - Twelve different species of neutral monohexosyl ceramides (CMHs) and two species
      of neutral monohexosyl ceramides were isolated from mycelium and yeast forms of
      Paracoccidioides brasiliensis, respectively, by a combination of ion-exchange
      chromatography, HPLC, and HPTLC. The glucosylceramides did not react with sera
      from patients with paracoccidioidomycosis (PCM). Carbohydrate analysis indicated
      that CMHs contain glucose. Analysis of 1H-NMR and mass spectrometry data suggest
      that the structure of the CMHs is Glcp beta 1-->Cer (mycelium forms present 12
      different ceramides and yeast forms present 2 different ceramides). The
      composition of the lipid moieties was analyzed by negative fast atom bombardment
      mass spectrometry. No glycosphingolipid other than glucosylceramide was detected
      in P. brasiliensis.

PMID- 9196543
TI  - Velocardiofacial syndrome with facial and pinna asymmetries.
AB  - This study reports some of the most important clinical features of the
      velocardiofacial syndrome (hypoplastic zygomatic arch, prominent nose with square
      nasal root, bilateral epicanthus, downslanting palpebral fissures, and learning
      disabilities) in a Brazilian boy presenting face and pinna asymmetries. These
      findings may facilitate the diagnosis of this syndrome.

PMID- 9196544
TI  - Lower density of antral somatostatin-immunoreactive cells in the digestive form
      of chronic Chagas' disease.
AB  - Patients with the digestive form of chronic Chagas' disease exhibit abnormally
      increased gastrin release, possibly caused by antral gastrin cell (G cell)
      hyperfunction. In order to identify the mechanisms underlying this abnormality,
      we used an immunohistochemical method to assess the population of antral
      somatostatin-producing cells (D cells) in chagasic patients, since somatostatin
      is known to be the main inhibitory factor of gastrin secretion. Samples (N = 11)
      of endoscopic antral biopsies taken from 16 Chagas' disease patients and 13
      control subjects were studied. Antral D and G cell populations were determined by
      an immunohistochemical technique using highly specific antibodies against
      somatostatin and gastrin. There was no significant difference between Chagas'
      disease and control groups regarding G cell population (number of cells/mm
      reported as median (range): 70.0 (23.7-247.0) vs 98.1 (52.7-169.4), P > 0.10). In
      contrast, the number of antral D cells in Chagas' disease patients was
      significantly lower than in controls (16.4 (6.9-54.4) vs 59.3 (29.6-113.8), P <
      0.05). Chronic superficial gastritis and infection with Helicobacter pylori were
      more frequent in chagasic patients than in controls, but there was no
      demonstrable association between these factors and the reduction of the number of
      antral D cells. These data suggest that reduction in the number of antral
      somatostatin-producing cells, which should lead to reduced inhibition of gastrin
      cell activity, may play a role in the increased gastrin secretion observed in
      Chagas' disease patients.

PMID- 9196545
TI  - Biliary and pancreatic stent blockage by bacterial biofilm: presentation of two
      cases.
AB  - Biliary and pancreatic stents are effective tools in the management of
      obstructive jaundice (both malignant and benign), pancreatic pseudocyst drainage,
      and as treatment for biliary and pancreatic fistulae. Unfortunately, stents may
      become blocked and require replacement in a number of patients. In the present
      study a blocked stent from a patient with transpapillary drainage of pancreatic
      pseudocyst and another from a patient with obstructive jaundice resulting from
      cancer of the head of the pancreas associated with Mirizzi syndrome were
      characterized by electron microscopy. Stent blockage was diagnosed by a pressure
      test and stent cultures were performed. Electron microscopy of the blocked stents
      revealed the sludge to consist of microcolonies of bacteria mixed with amorphous
      material, and cultures of both stents were positive for Klebsiella sp and E.
      coli.

PMID- 9196546
TI  - Resting and reflex heart rate responses during cholinergic stimulation with
      pyridostigmine in humans.
AB  - Dysfunction of the autonomic nervous system is of prognostic value for sudden
      death after acute myocardial infarction. Although the use of beta-blockers to
      counteract the adrenergic hyperactivity has been shown to decrease mortality in
      these patients, there have been no reports on the role of cholinomimetic drugs in
      the prognosis of patients after myocardial infarction. The present study was
      designed to investigate the effect of the administration of pyridostigmine
      bromide, a reversible anti-cholinesterase agent, on cardiac cholinergic activity
      assessed by the resting and reflex heart rate responses. Eight healthy volunteers
      were submitted to a conventional 12-lead electrocardiogram to obtain resting
      heart rate, and to three non-invasive cardiovascular tests: respiratory sinus
      arrhythmia, Valsalva maneuver and 4-sec exercise test. On two different days and
      following a randomized cross-over double-blind protocol, the experiments were
      performed before and 120 min after oral administration of either pyridostigmine
      bromide (30 mg) or placebo. Pyridostigmine increase (P < 0.05) the duration of
      the R-R intervals at rest (pre: 898 +/- 30 msec; post: 1019 +/- 45 msec; pre
      placebo: 916 +/- 26 msec; post: 956 +/- 28 msec; P > 0.05). Although the duration
      of the R-R intervals during the autonomic tests was also increased (P < 0.05),
      the derived indexes of maximal fluctuation during the maneuvers did not change.
      These results indicate that oral pyridostigmine produces tonic cardiac
      cholinergic stimulation while exerting no effect on its reflex changes. Further
      studies are needed to address the potential role of the administration of
      pyridostigmine in the prognosis of patients with acute myocardial infarction.

PMID- 9196547
TI  - Gallium-67 lung imaging and pulmonary clearance of 99mTc-DTPA aerosol in patients
      with amiodarone pneumonitis.
AB  - The aim of this study was to compare gallium-67 citrate lung imaging with the
      pulmonary clearance of 99mTc-DTPA (technetium 99m diethylenetriaminepentaacetic
      acid) in 9 patients with amiodarone pneumonitis (8 males and 1 female, aged 58 to
      76 years). The diagnosis of amiodarone pneumonitis was based on clinical and
      radiological grounds in all patients, and histological changes in seven. The mean
      values for the effective half-life of the pulmonary clearance of 99mTc-DTPA
      aerosol were below the normal range in all 9 patients, and lower than the values
      obtained previously for patients on a long-term amiodarone regimen without side
      effects. Positive gallium-67 accumulation was demonstrated in 7 of the 9
      patients. Two patients had negative gallium-67 imaging and increased alveolar
      capillary 99mTc-DTPA clearance; with corticosteroid therapy and discontinuation
      of amiodarone, their radiological changes and clearance became normal within 120
      days. In conclusion, when compared to gallium-67 lung imaging, the 99mTc-DTPA
      aerosol clearance is more advantageous because it is a much faster test than the
      gallium scan. This is essential for those patients suspected of amiodarone
      pneumonitis who need specific therapy as soon as possible. Moreover, the 99mTc
      DTPA aerosol clearance test appears to be a more useful diagnostic tool because
      it is positive even in those patients who have normal gallium-67 lung imaging.

PMID- 9196548
TI  - Late diagnosis of chronic renal failure.
AB  - A comparison was made between patients with a late diagnosis of chronic renal
      failure (1 month or less before starting dialysis, N = 96) and those with an
      early diagnosis (6 months or more, N = 45) in terms of the following aspects:
      referral characteristics during the pre-dialysis phase, demographic details and
      patient biochemistry prior to maintenance dialysis. Information was obtained by
      surveying consecutive patients with primary renal disease admitted to a
      university dialysis unit in Sao Paulo. Fifty-three percent of all patients
      surveyed had a late diagnosis. These patients had a lower median duration of
      symptoms (2 vs 6 months, P < 0.01) and were less likely to be referred for
      dialysis by a nephrologist (9% vs 51%, P < 0.001) than early diagnosis patients.
      In the early diagnosis group, 7 patients (16%) had follow-up care for less than 6
      months and 11 (24%) did not receive any follow-up; 21 patients (47%) did not
      follow a low-protein diet. At the start of dialysis, patients with a late
      diagnosis had higher blood pressure and a higher rate of pulmonary infections
      (19% vs 4%, P = 0.03). Mean concentrations of BUN, serum creatinine and potassium
      were significantly higher and mean blood hematocrit was lower for the late
      diagnosis group. After 3 months of dialysis, the mortality rate was higher in the
      late than in the early diagnosis group (22.9% vs 6.7%, P = 0.02). Late diagnosis
      of chronic renal failure and lack of adequate follow-up care, prior to the start
      of dialysis, are common. Interventions to promote early diagnosis of chronic
      renal failure and to improve compliance with regular nephrological follow-up can
      be important to reduce the morbidity and the mortality of patients with chronic
      renal insufficiency.

PMID- 9196549
TI  - Incomplete dominance of the low antibody response to Cryptosporidium parvum
      antigens in mice selected for high and low antibody responsiveness.
AB  - The humoral antibody response to Cryptosporidium was investigated in mice
      genetically selected for high (H) and low (L) antibody responsiveness. Groups of
      4-5 mice from two different selections, general primary (GP) and general
      secondary (GS), were studied. Following immunization with Cryptosporidium parvum
      antigens, the maximum levels of IgG in the HGP (X +/- SD = 1.13 +/- 0.35, N = 5)
      in the HGS (0.42 +/- 0.15, N = 4) lines, and of IgM in the HGP line (0.86 +/-
      0.53, N = 5) were significantly higher than those in their L counterparts (0.04
      +/- 0.02, N = 5; 0.05 +/- 0.02, N = 4 and 0.24 +/- 0.07, N = 5, respectively).
      These findings were similar to those reported for other immunogens. However, the
      IgG (0.22 +/- 0.05, N = 4) and the IgM (0.33 +/- 0.08, N = 4) responses to
      immunization of F1 (LGP x HGP) hybrids indicated an incomplete dominance of the
      low response, in contrast to the incomplete dominance of the high response
      described for many other antigens and representing an important exception. In
      addition, the H, L and F1 mice did not develop detectable infections when
      inoculated with live Cryptosporidium oocysts, supporting the view that a reduced
      or zero antibody production itself is not enough to permit the establishment of
      Cryptosporidium infection in adult mice.

PMID- 9196551
TI  - Identification and neutralization of biological activities in the venoms of
      Loxosceles spiders.
AB  - The biological activities of the venom of three species of spiders of the genus
      Loxosceles were studied (L. gaucho, L. laeta and L. intermedia). The
      dermonecrotic and lethal activities are shared by all three Loxosceles venoms.
      Only low levels of proteolytic, myotoxic and phospholipase A2 activities were
      demonstrable even when a large amount of venom was used. No direct hemolytic
      activity was detected. L. intermedia venom was the most lethal (LD50 0.48 mg/kg),
      the L. laeta venom was the least lethal (LD50 1.45 mg/kg) whereas L. gaucho venom
      showed an intermediate value (LD50 0.74 mg/kg). The anti-Loxosceles serum used
      (anti-arachnidic serum) was able to neutralize the most important activities
      (i.e., dermonecrotic and lethal activities) of the three venoms. SDS-PAGE and
      immunoblotting using the anti-arachnidic serum showed that almost all venom
      antigens were recognized by this antiserum. The possible mechanisms of action of
      the Loxosceles venom are discussed.

PMID- 9196550
TI  - Monoclonal antibodies against conserved epitopes of a 46-kDa protein from
      Neisseria meningitidis.
AB  - The purpose of the present study was to generate monoclonal antibodies (mAbs)
      against conserved epitopes of B meningococcus which could be applicable to the
      immunoscreening of bacterial meningitis. Three mAbs reactive to a 46-kDa protein
      conserved in eight sero-groups and several sero(sub)types of Neisseria
      meningitidis were selected for the present study. No reaction was detected with
      whole-cell lysates of Staphylococcus aureus. Streptococcus pneumoniae,
      Haemophilus influenzae type b or Escherichia coli. Two of these mAbs recognized
      46-kDa epitopes in four other Neisseria spp, and the third, MC3.13, cross-reacted
      only with N. lactamica. All mAbs reacted with whole-cell lysates from a N.
      meningitidis mutant strain lacking the class 1 outer membrane protein (43-47
      kDa). Immunoelectron microscopy revealed a cytoplasmic location for the 46-kDa
      protein. The MC3.13 monoclonal antibody is potentially applicable to a rapid
      screening of bacterial meningitis.

PMID- 9196552
TI  - Paraventricular nucleus administration of DuP753 or PD123319 inhibits the effects
      of angiotensin on water and sodium intake.
AB  - We determined the effects of DuP753 and PD123319 (both nonpeptides and selective
      antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1,
      Ala8]ANG II(a non-selective peptide antagonist of angiotensin receptors) on water
      and 3% NaCl intake induced by administration of angiotensin II (ANG II) into the
      paraventricular nucleus (PVN) of sodium-depleted Holtzman rats weighing 250-300
      g. Twenty hours before the experiments, the rats were depleted of sodium using
      furosemide (10 ng/rat, sc). The volume of drug solution injected was 0.5
      microliters over a period of 10-15 sec. Water and sodium intake were measured at
      0.25, 0.5, 1.0 and 2.0 h. Pre-treatment with DuP753 (14 rats) at a dose of 60 ng
      completely abolished the water intake induced by injection of 12 ng of ANG II (15
      rats) (6.4 +/- 0.6 vs 1.4 +/- 0.3 ml/2 h), whereas [Sar1, Ala8] ANG II (12 rats)
      and PD123319 (10 rats) at the doses of 60 ng partially blocked water intake (6.4
      +/- 0.6 vs 2.9 +/- 0.5 and 2.7 +/- 0.2 ml/h, respectively). In the same animals,
      [Sar1, Ala8]ANG II, DuP753, and PD123319 blocked the sodium intake induced by ANG
      II (9.2 +/- 1.6 vs 3.3 +/- 0.6, 1.8 +/- 0.3, and 1.4 +/- 0.2 ml/2 h
      respectively). These results indicate that both DuP753 and PD123329, administered
      into the PVN, blocked the water and sodium intake induced by administration of
      ANG II into the same site.

PMID- 9196553
TI  - Effect of intracerebroventricular injection of ramipril on the drinking response
      caused by injection of noradrenaline into the third ventricle.
AB  - We studied the effect of ramipril injected into the third ventricle (3rdV) on the
      control of water intake induced by injection of noradrenaline into the 3rdV of
      adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel
      cannula into the 3rdV. The injection volume was always 1 microliter and was
      injected over a period of 30-60 sec. Control animals were injected with 0.15 M
      NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the
      3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mircogram/microliter)
      injected into the 3rdV prior to isotonic saline produced no changes in water
      ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/microliter)
      after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The
      prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These
      data show that the inhibition of converting enzyme in the brain reduces the water
      intake induced by catecholaminergic stimulation. We conclude that the brain is
      able to transform the prodrug ramipril into the active drug ramiprilat.

PMID- 9196555
TI  - The Bender Gestalt test for 5- to 15-year old Brazilian children: norms and
      validity.
AB  - Norms for two modalities (normal and stress) of the Bender Gestalt test were
      developed for the neuropsychological assessment of children in the greater Rio de
      Janeiro area. For each modality, a measure of performance, a measure of speed and
      a measure of emotional disturbance were obtained. A total of 398 children (199
      males and 199 females), 5 to 15 years old, who were attending a public school in
      Niteroi were the subjects of this study. Analysis of the data revealed that age,
      but not sex, had a significant effect on performance, but not on speed, in both
      modalities such that older children made fewer errors than younger children.
      Also, the number of emotional indicators significantly decreased with age.
      Additionally, boys needed more time to complete the normal modality than girls,
      and showed a higher number of emotional indicators in both modalities. The Bender
      test was found to be valid in the sense that children who had failed at least one
      grade in school performed worse than those who had not. The number of emotional
      indicators was shown to be valid since it was significantly correlated with
      factors such as hyperactivity-conduct problem, and independent functioning, and
      inattention of the Composite Teacher Rating Scale (Brito GNO and Pinto RCA
      (1991). Journal of Clinical and Experimental Neuropsychology, 13: 417-418). We
      conclude that the Bender test is valid for use in schoolchildren, and the number
      of emotional indicators is valid as an index of psychopathology, but sex and age
      should be considered when using the norms in Brazil.

PMID- 9196554
TI  - Calretinin in the mouse superior colliculus originates from retinal ganglion
      cells.
AB  - We investigated the origin of the calretinin-immunoreactive fibers in the mouse
      superior colliculus. The dense plexus of calretinin-positive fibers in the
      superficial layers of the colliculus was completely eliminated after eye
      enucleation. Retrograde tracing combined with immunohistochemistry revealed many
      calretinin-positive small-to-medium retinal ganglion cells projecting to the
      colliculus. These results indicate that calretinin-containing ganglion cells are
      the source of this calcium-binding protein in the superficial layers of the
      superior colliculus.

PMID- 9196556
TI  - Tumor promoter-like activity of the molluscicidal latex of 'Crown-of-Thorns'
      (Euphorbia milii var. hislopii) in the V79 metabolic cooperation assay.
AB  - The latex of 'Crown-of-Thorns' (Euphorbia milii var. hislopii, syn. E. splendens)
      has been shown to be a potent plant molluscicide that could be used against the
      snails which are intermediate hosts of Schistosoma trematodes. However, a
      comprehensive toxicological evaluation of the latex is necessary before its large
      scale use in schistosomiasis control becomes possible. In fact, one cause for
      concern is the presence of tumor-promoting phorbol esters in several plants of
      the Euphorbiaceae family. Phorbol esters as well as a number of other known tumor
      promoters share the common property of inhibiting metabolic cooperation (i.e.,
      exchange of low molecular weight molecules via gap junctions) between Chinese
      hamster V79 cells in monolayer cultures. The present study was undertaken to
      determine if latex of E. milii presents tumor promoter-like activity is this
      short-term in vitro assay. Samples of lyophilized E. milii latex were tested at a
      noncytotoxic concentration range (1, 10, 50 and 100 micrograms/ml) in three
      independent experiments. 12-O-Tetradecanoylphorbol-13-acetate (10 ng/ml) was used
      as positive control. In all three assays, E. milii latex consistently inhibited
      metabolic cooperation between V79 cells at concentrations > or = 10
      micrograms/ml. These results that E. milii latex contains tumor-promoting
      substances. These findings suggest that the use of crude latex as a molluscicide
      may pose a carcinogenic hazard to people who are continuously exposed to the
      product.

PMID- 9196557
TI  - Effects of high doses of diazepam on carrageenin-induced paw edema in rats.
AB  - Benzodiazepine (BDZ) receptor sites play a relevant role in immune/inflammatory
      reactions. Acute BDZ treatments were shown not only to suppress cell
      proliferation in rat thymus but also to decrease TNF-alpha, IL-1 and IL-6 release
      from adult mouse macrophages. In the present investigation the effects of acute
      (10.0 and 20.0 mg/kg) and long-term (10.0 mg kg-1 day-1, for 21 days) diazepam
      treatment on carrageenin-induced paw edema were studied in rats. The results
      showed that acute treatment with high doses of diazepam decreased paw edema
      volume in a dose-dependent manner, and this effect was observed as early as 1 h
      after the administration of the 20.0 mg/kg dose and continued until the last
      measurement was performed (8 h). In contrast, long-term diazepam administration
      did not modify the phlogistic-induced edema. Taken together, these data show that
      1) acute diazepam treatment with high doses decreases the volume of the acute
      inflammatory paw edema developed by the organism as a response to carrageenin
      induced injury, and 2) long-term diazepam treatment induces tolerance to this
      effect. These results are discussed in the light of a possible effect of diazepam
      on the components of the rat cellular and humoral immune/inflammatory reaction
      such as T lymphocytes and/or interleukins.

PMID- 9196559
TI  - Effect of dipyrone, L-NAME and L-arginine on endotoxin-induced rat paw edema.
AB  - Paw edema was induced in male Wistar rats (200-250 g) by intraplantar (ipl)
      administration of 2.5 micrograms endotoxin (Etx). Etx, like carrageenin, produced
      two distinct edema formation phases, an early phase (75 min) followed by a late
      phase (7 h). We showed that the edema formation in the early phase was
      antagonized by dipyrone (80 mg/kg, i.p.) and indomethacin (1 mg/kg, i.p.) by 52%
      and 55%, respectively, and that the late phase was resistant to these drugs.
      These results suggest that in the early phase prostaglandins appear to be
      involved in the process. However, the activation of the kinin cascade leading to
      the release of other mediators may be involved in the increase of edema in the
      late phase. To test this hypothesis, we investigated whether the release of
      nitric oxide (NO) is involved in the mechanism of endotoxin-induced rat paw edema
      during the late phase, using N omega-nitro-L-arginine methyl ester (L-NAME) (50
      micrograms, ipl) as inhibitor of NO synthase and L-arginine (1 mg, ipl) as
      substrate of NO synthase. The paw edema induced by Etx was inhibited by L-NAME by
      56% and increased by L-arginine by 81%. Furthermore, L-arginine given in
      combination with L-NAME completely reversed the inhibition of Etx-induced edema
      produced by L-NAME. These results support the hypothesis that in the late phase
      NO production is associated with the edema evoked by Etx.

PMID- 9196558
TI  - Antinociceptive effects of stimulation of discrete sites in the rat hypothalamus:
      evidence for the participation of the lateral hypothalamus area in descending
      pain suppression mechanisms.
AB  - The sites in the rat hypothalamus where microinjection of morphine (5
      micrograms/0.5 microliters) or electrical stimulation depresses the tail
      withdrawal reflex to noxious heating of the skin were examined. Among other
      hypothalamic sites found to be sensitive to morphine or to an electrical
      stimulus, the posterior part of the lateral hypothalamic area (LHA) was the only
      portion of the hypothalamus that was strongly sensitive to both manipulations. A
      15-sec period of 35 microA sine-wave stimulation of the LHA significantly
      increased the latency of the tail reflex for periods up to 30 min. The effects of
      intraperitoneal administration of antagonists to opioids (naloxone), 5
      hydroxytryptamine (methysergide), noradrenaline (phenoxybenzamine), dopamine
      (haloperidol), and acetylcholine (atropine and mecamylamine) on the
      antinociceptive effects of LHA stimulation were also examined. Naloxone,
      methysergide, and atropine (all given at doses of 0.5 and 1.0 mg/kg) attenuated
      the effects of LHA stimulation in a dose-dependent manner. Phenoxybenzamine but
      not haloperidol (both at the dose of 1.0 mg/kg), was also effective but dose
      dependent curves could not be constructed. Mecamylamine (1.0 mg/kg) reduced the
      duration but not the peak effect of stimulating the LHA. We conclude that
      antagonism at the level of opioid, serotonergic, adrenergic, and muscarinic
      cholinergic receptors, but not dopamine or nicotinic cholinergic receptors,
      reduces the antinociceptive effects of LHA stimulation. This may imply that
      antinociception evoked from the LHA depends on the activation of descending
      pathways that relay in the mesencephalic periaqueductal gray matter and then in
      the nucleus raphe magnus and/or nucleus reticularis paragigantocellularis.

PMID- 9196560
TI  - Decreased basal and acute insulin-stimulated effect on the uptake of glucose and
      amino acid in vitro by thyroid glands from streptozotocin-diabetic rats.
AB  - Since experimental diabetes in rats and mice is associated with impairment of
      several aspects of thyroid function, we determined glucose and amino acid uptake
      in vitro by isolated thyroid glands from normal and streptozotocin-diabetic rats.
      Adult male Wistar rats weighing 150-200 g were used. Diabetes was induced by
      intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) and after
      five days only rats with blood glucose levels higher than 250 mg/dl were used.
      The thyroid glands were preincubated in Krebs-Ringer bicarbonate buffer in the
      presence or absence of insulin (0.7 nM to 7 muM) for 90 min and then incubated
      with the same concentration of the hormone or its vehicle plus 0.2 microCi of [1
      14C]-2-deoxy-D-glucose ([14C]DG) or [1-14C] methylaminoisobutyric acid
      ([14C]MeAIB) for 15 to 180 min. The uptake of [14C]DG or [14C]MeAIB by the
      thyroid glands of normal rats increased as a function of incubation time, and the
      presence of insulin (7 microM) induced a significant increase of labelled DG from
      3.30 +/- 0.11 to 4.16 +/- 0.12 and of labelled meAIB from 1.79 +/- 0.06 to 3.10
      +/- 0.17 tissue/medium ratio (T/M) and after 45 min of incubation. The lowest
      concentration of insulin that increased both [14C]DG and [14C]MeAIB transport was
      7 nM. Thyroid glands from STZ rats exhibited lower basal values of [14C]DG (4.03
      +/- 0.11 T/M) or [14C]MeAIB uptake (1.05 +/- 0.05 T/M) than glands from normal
      rats (4.62 +/- 0.13 and 1.70 +/- 0.08 T/M, respectively). Insulin produced a
      stimulatory effect on the transport of both substrates in STZ rats. However, the
      maximal stimulating concentration of the hormone did not restore [14C]DG and
      [14C]MeAIB uptake to control values (4.89 +/- 0.17 in STZ rats versus 5.44 +/-
      0.17 T/M in controls for [14C]DG, and 1.51 +/- 0.11 in STZ rats versus 2.19 +/-
      0.10 T/M in controls for [14C]MeAIB). These results indicate that insulin exerts
      a direct action on the thyroid gland, and its absence or reduction affects
      thyroid metabolism, contributing, at least in part, to the abnormality in thyroid
      function associated with diabetes mellitus.

PMID- 9196561
TI  - Pretreatment with phorbol ester and an LHRH agonist reduces testosterone
      production and protein kinase C activity in rat Leydig cells challenged with PDBu
      and LHRH.
AB  - We have investigated the role of protein kinase C (PK-C) in luteinizing hormone
      releasing hormone (LHRH)-induced testosterone secretion from purified rat Leydig
      cells (70-80-day old Sprague-Dawley rats) by pretreating the cells in vitro with
      200 mM phorbol 12,13-dibutyrate (PDBu) (a known procedure to down-modulate this
      enzyme in most cell types) and 1 muM [D-Ala6,Des-Gly10]-LHRH ethylamide, an LHRH
      agonist (LHRH-A). Following pretreatment we measured PK-C activity and secretion
      of testosterone in response to subsequent challenges with the PK-C activator PDBu
      (20-2000 nM) and with LHRH (0.001-1.0 muM) and the Ca(2+)-mobilizing secretagogue
      A23187 (0.1-100 microM) in the same cell preparation. PDBu and LHRH-A
      pretreatments caused a reduction in testosterone secretion in response to
      subsequent exposure to PDBu or LHRH. Both pretreatments decreased PK-C activity
      in crude and purified extracts of the same cells. The magnitude of reduction of
      the secretory response was greater than that of enzyme activity for both PDBu and
      LHRH-A pretreatment (68.9% reduction of testosterone secretion vs 54.7% reduction
      of PK-C activity in PDBu-pretreated cells and 78.6% reduction of testosterone
      production vs 36.6% reduction of PK-C activity in LHRH-A-pretreated cells). The
      effect of phorbol ester pretreatment on PDBu- or LHRH-stimulated testosterone
      secretion and PK-C activity was specific (no measurable effect with 4 alpha-PDBu,
      an inactive phorbol ester). While PDBu and LHRH-A pretreatment reduced Leydig
      cell responsiveness to PDBu or LHRH, the secretion of testosterone in response to
      the Ca2+ -mobilizing secretagogue A23187 was similar in PDBu- and LHRH-A
      pretreated and in control (non-pretreated) cells. We conclude that down
      modulation of protein kinase C by prolonged exposure of Leydig cells to phorbol
      esters or LHRH-A results in decreased PK-C activity and testosterone secretion.
      These results provide the first evidence that pretreatment with LHRH-A, which
      does not enter the cell, can affect the steroidogenesis and PK-C activity
      responses to PDBu (the intracellular ligand of PK-C).

PMID- 9196562
TI  - Propranolol stimulates testicular interstitial fluid formation and testosterone
      secretion in rats.
AB  - We investigated the effect of intratesticularly injected propranolol on
      testicular interstitial fluid (TIF) formation and on testosterone levels in the
      TIF of intact adult male Wistar rats (4-9 rats per group). dl-propranolol at
      doses of 0.6, 1.2, or 6.0 mg/kg was injected into the left (L) testis whereas the
      right (R) testis (control testis) received vehicle. dl-propranolol (6.0 mg/kg)
      caused a significant increase in both TIF volume (329%) and TIF levels of
      testosterone (257%) in the L testis but not in the R (control) testis 3 h post
      injection. In rats treated simultaneously with human chorionic gonadotropin (hCG,
      5 IU/rat, sc) the same dose or propranolol (6.0 mg/kg) significantly increased
      the stimulatory effect of hCG on testosterone secretion by 1.8-fold, but hCG did
      not modify the stimulatory effect of propranolol on TIF volume. These results
      demonstrate a direct stimulatory effect of propranolol on TIF volume and
      testosterone secretion, both under basal and hCG-stimulated conditions.

PMID- 9196563
TI  - Regulation of corticotropin-releasing hormone secretion by ACTH at different
      times after adrenalectomy.
AB  - This study was undertaken to determine the short-loop negative feedback at the
      hypothalamic site after adrenalectomy (ADX), when the hypothalamic-pituitary axis
      was a different set-points. Rats were submitted to the experimental procedure 3 h
      and 1, 3 and 14 days after bilateral ADX or sham surgery under ether anesthesia
      by the dorsal approach. ADX rats were supplied with 1.5% NaCl. After
      decapitation, plasma samples were collected and corticosterone (B) and
      adrenocorticotrophic hormone (ACTH) concentrations were determined by
      radioimmunoassay (RIA). Using in vitro incubation of the median basal
      hypothalamus (MBH) fragment we studied the hypothalamic corticotrophin-releasing
      hormone (CRH) release under basal conditions and under the inhibitory effect of
      ACTH. Hypothalamic CRH secretion, determined by direct RIA, without extraction
      and reported as pg CRH/MBH per 1 h incubation, was inhibited by ACTH
      administration in a dose-dependent manner, as demonstrated by a significant
      negative correlation obtained by linear regression analysis of CRH secretion as a
      function of ACTH dose. However, the percentage of inhibition of CRH secretion was
      higher at 1 and 3 days than at 14 days after ADX. In conclusion, these in vitro
      studies demonstrated that ACTH suppressed basal CRH secretion in a dose-dependent
      manner, an effect compatible with a short-loop feedback mechanism. Furthermore,
      we demonstrated variable suppressibility of CRH secretion by ACTH at different
      times after ADX.

PMID- 9196565
TI  - Adults with inherited disorders of intermediary metabolism.

PMID- 9196564
TI  - Providing a vascular service.

PMID- 9196566
TI  - The role of nuclear medicine in children.
AB  - Nuclear medicine studies have an important role to play in the diagnosis,
      treatment and follow-up of several paediatric conditions. This article highlights
      this role and indicates areas of potential growth.

PMID- 9196568
TI  - Endometrial cancer.

PMID- 9196567
TI  - Chest wall resection and reconstruction.
AB  - Chest wall reconstruction may be required after resection of malignant tumours,
      radiation injuries, massive trauma or infection. The ideal reconstruction should
      provide enough stability in the chest wall to allow adequate, spontaneous
      ventilation, while protecting intrathoracic organs, and be cosmetically
      acceptable. Recent developments have enabled the reconstruction of defects of
      almost any size with minimal functional disturbance.

PMID- 9196569
TI  - Work-based learning.

PMID- 9196570
TI  - Distance learning courses at the Royal College of Surgeons.

PMID- 9196571
TI  - Advanced trauma life support in the UK: 8 years on.

PMID- 9196572
TI  - Care of the critically ill surgical patient courses of the Royal College of
      Surgeons.

PMID- 9196573
TI  - So you want to train in ophthalmology.

PMID- 9196574
TI  - Interferon beta: the current position.
AB  - Treatments that reduce disease activity in multiple sclerosis are now available,
      but it is not known how these agents will modify the development of disability in
      the long term. Published trials of the use of interferon beta failed to detect
      any clinically relevant reduction in accumulation of disability during the study
      period. Should patients therefore be prescribed these compounds?

PMID- 9196575
TI  - Tracheal intubation: how to do it.
AB  - Tracheal intubation can be life saving, but it is a dangerous procedure if the
      correct conditions have not been established. Repeated futile attempts at
      intubation should not be made: oxygenating the patient with a face mark or
      laryngeal mask airway should become a priority in this situation.

PMID- 9196576
TI  - Whither Whitley?
AB  - Whitley in the NHS has increasingly become perceived as an impediment to
      progress. This article considers this perception in the context of the origins of
      Whitleyism, its contribution to the management of health services and the staff
      working with them, and whether it has kept pace with the change process in the
      NHS in recent years.

PMID- 9196578
TI  - Management of a boy with extensive burns and a partly closed tracheostomy.

PMID- 9196577
TI  - Identification of disease genes.

PMID- 9196579
TI  - Animal organ transplants.

PMID- 9196580
TI  - The effects of changing patterns in service provision on the management of
      cancer.

PMID- 9196582
TI  - Decision-making in surgery: acute postoperative renal failure.

PMID- 9196581
TI  - Interventional radiology in palliative medicine.
AB  - Substantial developments in interventional radiology over the last two decades
      have resulted in the introduction of new methods of treatment for patients with
      advanced malignancy. These new minimally invasive techniques avoid the need for
      prolonged hospital inpatient care.

PMID- 9196583
TI  - The Health of the Nation 4 years on: what have we done, what must we do?
AB  - The Health of the Nation programme has been running for 4 years. We have made
      real progress on many of the targets but on a few key ones we appear to be having
      little impact. The concern is that we are storing up problems for the future. To
      tackle these, we need a sustained programme of action, and clinicians have an
      important role to play.

PMID- 9196584
TI  - Non-invasive ventilation in chronic obstructive pulmonary disease.

PMID- 9196585
TI  - Non-invasive ventilation in neuromuscular disease.

PMID- 9196586
TI  - Non-invasive ventilation in the intensive care unit and operating theatre.

PMID- 9196587
TI  - Respiratory dreams and nightmares.

PMID- 9196588
TI  - Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the most common cancer in males. Surgery is the only
      curative treatment, but is applicable in only 10-15% of patients. Systemic
      chemotherapy, transarterial embolization or chemo-embolization can only palliate.
      In the future, selective internal radiation may have a role in downstaging
      inoperable hepatoma to operable tumour.

PMID- 9196590
TI  - Trusts and their uses.

PMID- 9196589
TI  - Opioid analgesics.
AB  - This article discusses recent developments in opioid pharmacology. Selective
      activity at different opioid receptors promises, but has not yet provided, a
      strong analgesic without opioid side-effects. The startling pharmacokinetic
      profile of the new esterase-metabolized intravenous opioid, remifentanil, is
      reflected in the rapid onset of effect and short, predictable recovery,
      independent of duration of infusion.

PMID- 9196592
TI  - DNA sequencing.

PMID- 9196591
TI  - Training in NHS management for doctors.
AB  - All doctors are managers by virtue of their role. This article explores the
      knowledge, skills and attitudes required by doctors if they are to make the
      contribution to individuals and society that they wish, through the direct and
      indirect deployment of resources and the influencing of organizational decisions.
      The nature and source of various training options are discussed.

PMID- 9196593
TI  - Changing patterns in cancer service provision.

PMID- 9196594
TI  - Post-traumatic stress counselling.

PMID- 9196595
TI  - Post-traumatic stress counselling.

PMID- 9196596
TI  - Specialist surgical nursing assistant.

PMID- 9196597
TI  - Glycodelins as regulators of early events of reproduction.

PMID- 9196598
TI  - Non-parametric deconvolution provides an objective assessment of GH
      responsiveness to GH-releasing stimuli in normal subjects.
AB  - OBJECTIVE: Deconvolution analysis has been proposed as an effective method for
      analysing the physiology of GH secretion. In the literature, it has been applied
      to spontaneous secretion data characterized by long and uniform sampling
      paradigms. In the present study we investigated the applicability of non
      parametric deconvolution to the analysis of response-to-stimuli (RTS) data
      characterized by infrequent and non-uniform sampling. PATIENTS: Thirty-six
      healthy adult male volunteers (age range 24-37 years) were randomly subdivided
      into two groups (group I, n = 30; group II, n = 6). DESIGN: Subjects of group I
      were tested with a single 1 microgram/kg body weight GH-releasing hormone (GHRH)
      bolus, administered at 0 minutes. Subjects of group II were tested, in random
      order, with a 4- or 5-day interval, with (1) two consecutive 1 microgram/kg body
      weight GHRH boluses at 0 and 120 minutes and (2) two consecutive 1 microgram/kg
      body weight hexarelin boluses, administered at 0 and 120 minutes. MEASUREMENTS:
      GH levels were determined at 0, 15, 30, 45, 60, 90 and 120 minutes (group I) and 
      30, 0, 15, 30, 45, 60, 120, 135, 150, 165, 180 and 240 minutes (group II). A
      numerically efficient regularization-based non-parametric deconvolution algorithm
      incorporating non-negativity constraints was used to estimate the time profile of
      the instantaneous secretion rate (ISR). Confidence limits allowing for both
      measurement error and kinetic model uncertainty were computed using a Monte-Carlo
      procedure. In order to validate the deconvolution method, a simulated benchmark
      problem was set up. RESULTS: The analysis of the benchmark problem showed that
      the proposed method is capable of providing an accurate reconstruction of the ISR
      (as measured by the root mean square (RMS) error). Moreover, it appeared that
      reliable confidence limits cannot be obtained unless the kinetic model
      uncertainty is taken into account. The analysis of the data showed a clear rise
      in the ISR subsequent to the first bolus (either GHRH or hexarelin), with most of
      the response occurring within 60 minutes of the stimulus. In group I, it was also
      seen that discarding the samples collected at times 90 and 120 minutes only
      marginally affected the estimate of the cumulated ISR over 0-60 minutes (the
      variation was always less than 3%). The analysis of GH responsiveness to repeated
      stimuli (group II) showed that the amount of hormone secreted after the second
      bolus was clearly reduced in comparison with the elicited by the first stimulus,
      most of the response occurring within 60 minutes of the injection. The amount of
      GH secreted after the second stimulus ranged from 13 to 36% (GHRH 17-36%;
      hexarelin 13-36%) of the overall amount of hormone secreted after time 0 minutes.
      CONCLUSIONS: Even with relatively few samples, non-parametric deconvolution of
      response-to-stimulus data is capable of providing a reliable, smooth and non
      negative estimate of the GH instantaneous secretion rate that offers a realistic
      representation of the GH secretory dynamics. The non-parametric approach compares
      favourably with respect to discrete deconvolution methods, that yield
      discontinuous instantaneous secretion rates profiles, and parametric methods that
      would require more stringent assumptions on the shape of the instantaneous
      secretion rate. When assessing confidence limits it is essential to take into
      account both measurement error and kinetic model uncertainty. Using deconvolution
      in normal subjects, the estimated instantaneous secretion rate between 0 and 60
      minutes is scarcely affected by samples taken after time 60 minutes. Since most
      of the secretory response takes place during this time interval, there is
      motivation for investigating the use of shorter sampling protocols in conjunction
      with deconvolution analysis. Although pulse detection and the assessment of the
      shape of spontaneous pulses have not been investigated, it could be interesting
      to apply non-parametric deconvolution to spontaneous sec

PMID- 9196599
TI  - How does one get at glandular secretion, when only hormone concentrations are
      measured?

PMID- 9196600
TI  - An account of the quality of life of patients after treatment for non-functioning
      pituitary tumours.
AB  - OBJECTIVE: Studies assessing quality of life in GH-deficient adults have shown
      varying results. This may be due to a number of factors including varying causes
      of GH deficiency, the use of radiotherapy in treatment and patient selection. We
      aimed to assess whether anterior pituitary hormone deficiency or external
      pituitary radiotherapy influenced the quality of life of patients with non
      functioning pituitary tumours. PATIENTS: We studied 48 patients treated and under
      follow-up for non-functioning pituitary tumours on standard hormone replacement
      therapy excluding GH. There were 21 females and 27 males with a mean age of 59 +/
      12 years. We also studied 42 control patients who had undergone mastoid surgery
      and were followed at least annually. There were 17 females and 25 males with a
      mean age of 61 +/- 14 years. DESIGN: All patients attended a research clinic and
      completed the Short Form 36 (SF36) and General Well Being Schedule (GWBS) to
      assess quality of life. Thyroid function tests, IGF1 and IGFBP3 were measured on
      all patients. Gonadotrophin and cortisol measurements were made on the patients
      with pituitary disease where appropriate. RESULTS: IGF1 and IGFBP3 levels were
      lower in the pituitary patients compared with controls: 104 +/- 98 vs 143 +/- 37
      micrograms.l (P < 0.0001) and 2.9 +/- 0.75 vs 3.3 +/- 0.52 mg/l (P < 0.004).
      There were no significant differences in the quality of life scores between the
      pituitary patients and the control subjects. There was also no difference in
      quality of life between pituitary patients with two or more hormone deficiencies
      (n = 29) compared with controls. Patients who had received radiotherapy (n = 18),
      when compared with controls, had a decreased mental health score using the SF36
      71 +/- 21 vs 81 +/- 17 (P < 0.05) and decreased total GWBS score 70 +/- 20 vs 82
      +/- 17 (P < 0.05). Subscore analysis of GWBS showed this to be due to depression
      and decreased control of emotions. CONCLUSIONS: We found that the quality of life
      of patients treated and under follow up for non-functioning pituitary tumours was
      similar to that of patients treated by mastoid surgery and under similar follow
      up. The pituitary patients deficient in two hormones and thus most likely to be
      GH deficient were also similar to the controls. These results suggest that adding
      GH replacement in this patient group may not be routinely indicated for
      improvement in quality of life and needs careful assessment. Patients who had
      received radiotherapy were more depressed and anxious than controls. Further
      investigation into the psychological and psychomotor effects of radiotherapy in
      this group of patients is required.

PMID- 9196601
TI  - Growth hormone deficiency and quality of life in hypopituitary adults.

PMID- 9196602
TI  - Treatment of macroprolactinoma with cabergoline: a study of 85 patients.
AB  - OBJECTIVE: Cabergoline is now established as an effective and well-tolerated
      treatment for prolactinoma. However, there are relatively few published data on
      the treatment of macro-, as opposed to micro-, prolactinoma. We have therefore
      reviewed the efficiency and safety of cabergoline in the treatment of patients
      with prolactin-secreting macroadenomas treated on a compassionate basis. STUDY
      DESIGN AND PATIENTS: Eighty-five patients with prolactin-secreting macroadenomas
      were treated with cabergoline 0.25 to 10.5 mg per week (median 1 mg) given to one
      to seven doses. Treatment durations ranged between 3 months and 8 years. Sixty
      five patients (32 intolerant, 16 resistant) had been treated previously with
      other dopamine agonists. Pretreatment prolactin levels ranged between 80 and 8300
      micrograms/I and tumour maximum diameters were between 11 and 42 mm.
      MEASUREMENTS: Serum prolactin, visual fields if initially abnormal, occurrence of
      menses or return of libido and potency, blood chemistry and adverse events were
      assessed at 1 month and then at 3-month intervals during treatment. Pituitary
      computed tomography or magnetic resonance imaging was usually repeated at 3
      months and 1 year, then yearly, in most patients (n = 62). RESULTS: Normalization
      of prolactin levels was achieved in 52 patients (61.2%) and a prolactin decrease
      of at least 75% of pretreatment values occurred in 24 others (28.2%). Of the 20
      de novo patients, 17 had prolactin normalized and the remainder had at least 75%
      reduction. Disappearance of tumour image was found in eight of 62 evaluable
      patients (12.9%) and reduction of the largest diameter by at least 25% in another
      33 (53.2%), with an overall success rate of 66.1%; among the 17 evaluable de novo
      patients the success rate was 82.3%. Fifteen of 21 patients who failed to show
      tumour shrinkage had previously demonstrated resistance/intolerance to other
      prolactin-lowering treatments. Of the 12 patients with visual field defects at
      baseline, six normalized and two showed an improvement. Menses resumed during
      cabergoline treatment in 79.5% of premenopausal women. Restoration of potency was
      reported by seven of eight evaluable men. Adverse events were recorded in 24.7%
      of cases, four of whom (4.7%) discontinued treatment. CONCLUSIONS: Although the
      present data were not obtained in a formal study we conclude that cabergoline is
      an effective and well-tolerated treatment for macroprolactinoma patients.

PMID- 9196603
TI  - The relationship between overnight GH levels and insulin concentrations in
      adolescents with insulin-dependent diabetes mellitus (IDDM) and the impact of
      recombinant human insulin-like growth factor I (rhIGF-I).
AB  - OBJECTIVE: We examined the relationship between GH concentrations and free
      insulin concentrations, used as an index of insulin sensitivity, before and after
      recombinant human insulin-like growth factor I (RhIGF-I) administration in
      adolescents with insulin-dependent diabetes mellitus (IDDM). DESIGN AND PATIENTS:
      Growth hormone concentrations were assessed by a peak detection programme
      (Pulsar) on a control night (2000 h-0800 h) and a night when rhIGF-I administered
      in a subcutaneous dose of 40 micrograms/kg at 1800 h to 16 adolescent subjects.
      Stable euglycaemia was maintained by a continuous intravenous insulin infusion
      and changes in free insulin levels on the two nights were compared with growth
      hormone data. RESULTS: Mean overnight GH concentrations (2000 h-0800 h) on the
      control night were positively related to glycated haemoglobin (Hba1)
      concentrations (r = 0.63; P < 0.01) and were reduced following rhIGF-I
      administration (24.9 +/- 3.6 mU/I on the control night versus 17.4 +/- 2.2 mU/I
      after administration, P = 0.01). The mean GH pulse amplitude on the control night
      was related to the change in GH levels after rhIGF-I (rs = -0.66, P < 0.001).
      Multiple regression analysis revealed that mean GH pulse amplitude was the only
      determinant of free insulin concentrations (0500 h-0700 h on both study nights (P
      < 0.01). The percentage change in mean growth hormone pulse amplitude between the
      two nights was related to the percentage reduction in free insulin concentrations
      (r = 0.53, P = 0.03). CONCLUSIONS: Growth hormone pulse amplitude is related to
      early morning insulin sensitivity in adolescents with IDDM on control nights and
      after rhIGF-I administration. The reduction in insulin levels following rhIGF-I
      may be linked to the change in GH pulse amplitude and not just to direct insulin
      like actions. Individuals with the higher GH (and thus HbA1 levels) were most
      sensitive to the GH-suppressive effects of rhIGF-I.

PMID- 9196604
TI  - Urinary growth hormone following exercise to assess growth hormone production in
      adults.
AB  - OBJECTIVE: The insulin stress test (IST) is the most commonly used test to assess
      the GH reserve in children and adults. It is a time-consuming, expensive and
      potentially dangerous test. We investigated whether measurement of urinary growth
      hormone excretion following exercise would prove on reliable method to diagnose
      adult GH deficiency. DESIGN: Healthy volunteers underwent a standard IST to
      confirm GH secretion. Using a standardized exercise protocol on a treadmill, the
      urinary excretion of GH was measured. Three patients confirmed as GH deficient by
      an IST were exercised during the same exercise protocol and their urinary
      excretion of GH was measured. PATIENTS: Ten healthy volunteers and three patients
      with hypopituitarism were evaluated. MEASUREMENTS: A standard IST was performed
      on both healthy volunteers and patients, with measurements of plasma GH and
      plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios
      were measured before and after IST. On a separate visit, healthy volunteers and
      patients were exercised on the treadmill with measurements of plasma GH and
      cortisol. Urinary GH and GH/CR ratios were measured before and after exercise.
      RESULTS: There was at least a two-fold increase in urinary GH and GH/CR ratios
      following exercise in all healthy adults. By contrast, patients with GH
      deficiency showed no rise in urinary GH or urinary GH/CR ratios following
      exercise. CONCLUSIONS: Measurements of urinary GH following exercise can
      distinguish between GH-deficient adults and healthy volunteers. Urinary GH
      excretion can be measured over a timed interval following exercise or can be
      expressed as the GH/CR ratio. This can be measured on a single sample following
      exercise and can be used to diagnose GH deficiency. The exercise test employed
      for this study is arduous. We are therefore performing further studies with a
      less strenuous exercise protocol with a view to designing a 'patient-friendly'
      exercise test for GH deficiency in adults.

PMID- 9196605
TI  - Diminished adrenal androgen secretion in familial glucocorticoid deficiency
      implicates a significant role for ACTH in the induction of adrenarche.
AB  - OBJECTIVE: The mechanism of adrenarche is controversial, and there have been
      competing claims that its origin is in the hypothalamo-pituitary axis or in the
      adrenal gland itself. ACTH is proposed inducer of adrenarche so patients with
      ACTH resistance due to be familial glucocorticoid deficiency syndrome provide a
      model to clarify the degree to which ACTH is involved in the regulation of
      adrenal androgen secretion during adrenarche. DESIGN: Random analysis of plasma
      adrenal androgens and urinary adrenal androgen output in treated patients with
      familial glucocorticoid deficiency. PATIENTS: Eleven patients (6 males and 5
      females, aged 6.5-21.6 years, 4 prepubertal, minimum bone age 9 years) with
      familial glucocorticoid deficiency were studied. In 6, mutations, in the coding
      region of the ACTH receptor are the cause of their ACTH resistance. In the
      remaining 5 the receptor was normal. MEASUREMENTS: Physical examination, basal
      serum cortisol, basal plasma ACTH, serum cortisol after stimulation with 250
      micrograms ACTH(1-24), plasma dehydroepiandrosterone-sulphate (DHEAS) and plasma
      androstenedione (A4), total urinary androgen excretion and single-stranded
      sequencing of the coding region of the ACTH receptor. RESULTS: DHEAS was
      undetectable in 8, and detectable but below the age-matched reference values in 3
      patients. A4 was measured in 10 patients, and in 3 patients (2 in late puberty)
      was found to be subnormal whereas in the remaining 7 patients A4 was normal for
      age and pubertal stage consistent with the gonadal contribution to peripheral A4
      levels. Significantly diminished output of urinary adrenal androgen metabolites
      in 3 patients confirmed the results found in serum. The lack of adrenarche was
      independent of the presence of a mutation within the ACTH receptor and of the
      severity of glucocorticoid deficiency. Despite adequate glucocorticoid
      replacement therapy ACTH levels remained elevated in 10 of the 11 patients.
      CONCLUSIONS: Although reduced adrenocortical inner zone cell number may
      contribute to the lack of adrenarche, in some patients there appears to be a
      discrepancy between partial glucocorticoid deficiency and significantly
      diminished adrenal androgen secretion. These data imply a significant
      contribution of ACTH to the regulation of adrenarche in normal children either by
      having a priming effect on the adrenal gland or by acting in concert with other
      adrenal androgen stimulating factors.

PMID- 9196606
TI  - Post-menopausal and chronological age have divergent effects on pituitary and
      hypothalamic function in episodic gonadotrophin secretion.
AB  - OBJECTIVE: Ageing is known to reduce gonadotrophin secretion in post-menopausal
      women. To what extent the hypothalamus and pituitary are involved in this process
      is not clear. The aim of this study was to compare pulse characteristics of FSH
      and LH in relation to chronological and post-menopausal age. Base on the
      gonadotrophin to GnRH, we assessed the extent to which pituitary and/or
      hypothalamic ageing is responsible for the observed changes. DESIGN: Blood
      samples were obtained from post-menopausal women every 10 minutes for 6 hours.
      Subsequently, 100 micrograms GnRH was administered intravenously and blood
      samples taken after 30, 60 and 90 minutes. PATIENTS: Twenty healthy women aged 47
      72 years and between 1 and 30 years after the menopause. MEASUREMENTS: Plasma LH
      and FSH were measured by immunoradiometric assay. Pulses were identified by a
      computerized pulse detection program. End points were the mean number and
      amplitude of pulses, the mean LH and FSH concentrations during the 6-hour study
      period and the maximal LH and FSH increments following GnRH. RESULTS: Mean LH and
      FSH levels did not change with chronological age but the LH pulse frequency
      declined significantly and the response to GnRH increased. Mean LH levels
      declined with post-menopausal age without alteration in LH pulse frequency but
      with a significant decrease in pituitary LH response to GnRH. FSH levels remained
      unchanged. CONCLUSIONS: Post-menopausal ageing seems to have a major suppressive
      effect on pituitary gonadotroph function, while chronological ageing mainly
      affects the hypothalamic regulation of LH secretion.

PMID- 9196607
TI  - The effect of treatment variables on mood and social adjustment in adult patients
      with pituitary disease.
AB  - OBJECTIVE: Studies of mood in hypopituitary adults have yielded inconsistent
      results. This investigation was carried out to investigate whether treatment
      characteristics may be responsible for the inconsistent results. DESIGN AND
      MEASUREMENTS: We compared three groups of patients with a group of matched
      healthy controls on self-report measures of mood and social adjustment (Beck
      depression inventory, State-trait anxiety inventory, Social adjustment scale
      (modified)) and a measure of quality of life (Nottingham health profile, NHP).
      PATIENTS: The patient groups were those treated with transfrontal surgery (n =
      23), transsphenoidal surgery (n = 23) or medication only (n = 23). In addition, a
      close informant of each subject was asked to complete a social adjustment measure
      about the subject's level of adjustment. RESULTS: On the self-report mood and
      social adjustment measures and the emotion sub-scale of the NHP, the
      transsphenoidal and medication patient groups rated themselves as being more
      depressed, anxious and having poorer social adjustment than the transfrontal or
      control groups. The close informants, however, rated all three patient groups as
      having poorer social adjustment than the controls. Patients treated with surgery
      and without radiotherapy reported fewer symptoms of depression than those treated
      with radiotherapy. Realistic self-appraisal of social adjustment in surgical
      patients was found only in those treated with transsphenoidal surgery without
      radiotherapy. CONCLUSIONS: Patients treated for pituitary tumour, excepting those
      treated with transfrontal surgery and to a lesser extent those treated with
      radiotherapy, suffer from mild mood disturbance and self-perceived decreased
      social adjustment. All patient groups are seen by others as having decreased
      social adjustment, raising the possibility that the transfrontal patients and
      possibly those who have had radiotherapy, lack insight. This may explain some of
      the discrepancies in the previous literature and needs to be taken into account
      when using self-report measures with these patients.

PMID- 9196609
TI  - Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of
      dexfenfluramine.
AB  - OBJECTIVE: Hyperactivity of the HPA axis is a possible mechanism underlying
      abdominal obesity. We aimed to evaluate in premenopausal women with abdominal
      obesity, (i) the hypothalamic-pituitary-adrenal (HPA) axis responses to direct
      pituitary stimulation with corticotrophin releasing hormone (CRH) and to opioid
      blockade with naloxone, and (ii) the interaction between short-term
      serotoninergic activation with dexfenfluramine (dF), a serotonin-release agonist,
      and these responses. DESIGN AND SUBJECTS: Eight obese women (mean BMI, 35 kg/m2)
      with waist to hip ratio (WHR) > 0.85 were tested with CRH (1 microgram/kg i.v.)
      and naloxone (125 micrograms/kg i.v.) before and at the end of two treatment
      periods with dF (15 mg twice daily for 7 days) and placebo (washout 7 days) in a
      cross-over design. Eight normal weight control women were tested with CRH and
      naloxone. RESULTS: Prior to treatment, ACTH and cortisol responses to naloxone
      (areas under the curve) were significantly higher in obese women then in control
      women (P = 0.027 and P = 0.035 respectively) dF treatment resulted in significant
      (P < 0.05) reduction of ACTH and cortisol increments. In contrast, ACTH and
      cortisol responses to CRH were not significantly different in obese and control
      subjects and were unaffected by dF treatment. CONCLUSION: We conclude that women
      with abdominal obesity have hyperreactivity of the HPA axis to opiod blockage and
      that dexfenfluramine treatment reduces this hyperactivity.

PMID- 9196608
TI  - Growth response and levels of growth factors after two years growth hormone
      treatment are similar for a once and twice daily injection regimen in girls with
      Turner syndrome. (Dutch Working Group on Growth Hormone).
AB  - GH is known to improve height velocity in girls with Turner syndrome (TS) but the
      optimal dosage regimen has yet to be defined. OBJECTIVE: We attempted to improve
      the growth response by trying to mimic normal pulsatile GH secretion more
      closely. DESIGN: In a 2-year study the effect of fractionated twice daily (BID)
      was compared with once daily (OD) s.c. injections of a total GH dose of 6
      IU/m2/day. BID injections were administered as two-thirds at bedtime and one
      third in the morning. The subjects concurrently received low dose ethinyl
      oestradiol (0.05 mg/kg/day, orally). SUBJECTS: Nineteen girls with TS aged 11
      years or over, who were previously involved in a 10-week GH cross-over study.
      MEASUREMENTS: Height and bone age were evaluated in relation to untreated Turner
      reference data. Final height (FH) was predicted using the Bayley and Pinneau (BP)
      method, the modified index of Potential Height (mIPHRUS), and a recently
      developed Turner-specific method (PTSRUS) based on regression coefficients for
      height (H), chronological age (CA) and bone age (BA). Plasma levels of GH, GHBP,
      IGF-1, and IGFBP-3 were determined by RIA. RESULTS: After 2 years treatment the
      growth response expressed as HV, HVSDS, the change in HSDSCA, the gain in height
      over estimated untreated values and in FH prediction all showed significant
      improvements. Although mean values tended to be higher with OD injections,
      significant differences between groups were not found. Bone maturation was
      similar between groups and compared with untreated estimated values. Independent
      of treatment group, the change in HSDSCA after 2 years of GH treatment was
      related negatively to the baseline CA and HSDSCA, and positively to BA delay at
      baseline. After 18 months of GH treatment the significant decrease in GHBP plasma
      levels observed after 6 months was no longer significant. In contrast, IGF-1 and
      IGFBP-3 plasma levels and the IGF-1 to IGFBP-3 ratio increased significantly
      during 18 months GH therapy. None of these growth related factors showed a
      difference between groups in their 18 months change. Relevant side-effects were
      not observed during the first 2 years of GH treatment. CONCLUSIONS: The present
      growth data are in conformity with the data of the earlier 24-hour GH profiles.
      The growth response and plasma levels of growth related factors after 2 years GH
      on a total dose of 6 IU/m2/day in combination with low-dose oestrogens were not
      significantly different between the once daily and the twice daily GH injection
      regimen.

PMID- 9196610
TI  - High incidence of positive autoantibodies against thyroid peroxidase and
      thyroglobulin in patients with sarcoidosis.
AB  - OBJECTIVE: Although abnormalities of the humoral immune system, such as increased
      immunoglobulin production, are known in sarcoidosis, the relationship between
      sarcoidosis and autoimmune disorders in uncertain. We studied the incidence of
      thyroid autoantibodies and the prevalence of Hashimoto's thyroiditis in patients
      with sarcoidosis. PATIENTS AND MEASUREMENTS: Sixty-two patients with pulmonary
      sarcoidosis, diagnosed by a combination of clinical, radiographic and
      histological findings were studied. As controls, three groups of subjects aged 40
      and over without a known history of thyroid disease (60 patients with pulmonary
      diseases other than sarcoidosis, 88 hospital employees and 82 company workers),
      were also analysed. Antibodies against thyroid peroxidase (TPO-Ab) and purified
      thyroglobulin (Tg-Ab) were measured by radioimmunoassay and antibodies against
      microsomal antigen (MCHA) and thyroglobulin (TGHA), by haemagglutination.
      RESULTS: Seventeen of 62 patients (27.4%) had either positive TPO-Ab or Tg-Ab or
      both. All the patients with positive thyroid autoantibodies were of middle or
      advanced age, and the incidence of positive TPO-Ab/Tg-Ab in patients with
      sarcoidosis aged 40 and over was 54.5% in males, 32.4% in females and 37.8%
      overall. The prevalence was significantly higher in males compared to age-matched
      control males (0-7.7% in the controls), and in female patients was twice that
      found in controls (11.8-16.3%). Seven patients had Hashimoto's thyroiditis,
      indicating that the prevalence was 11-3%, and much higher than that previously
      reported. CONCLUSIONS: The data show a remarkably high incidence of thyroid
      autoantibodies in patients of middle of advanced age with sarcoidosis, especially
      in males, and a higher prevalence of Hashimoto's thyroiditis than in previous
      reports.

PMID- 9196611
TI  - The safety profile of GH replacement therapy in adults.
AB  - OBJECTIVE: The benefits of GH replacement in GH-deficient adult patients are
      becoming accepted but the safety profile continues to be defined. The GH
      deficiency in adults may have arisen i either childhood or during adult life and
      these two groups differ with regard to history of disease. The aid of the present
      report was to study differences in safety profile between these two groups during
      long-term replacement therapy with recombinant human GH (hGH). Possible factors
      which placed a patient at risk of experiencing an adverse event were also
      examined. PATIENTS AND DESIGN: GH-deficient adult patients were randomized into
      two study protocols, differing only in age of onset of the GH deficiency
      syndrome. There were 98 patients with adult-onset and 67 patients with childhood
      onset GH deficiency. Each study consisted of a 6-month double-blind placebo
      controlled phase followed by an open-label hGH treatment phase. Glucose
      tolerance, incidence of treatment-emergent adverse events and relationship to IGF
      status were studied throughout the 36 months of treatment. RESULTS: Human growth
      hormone-related adverse events were reported less commonly in childhood-onset
      patients compared with adult-onset patients. Adult-onset patients who continued
      into the open-label therapy phase reported an increased incidence of arthralgia,
      myalgia and paraesthesia. There were significant increases in fasting glucose
      with hGH therapy but values remained within the normal range. Hypertension was
      reported in 7.7% of adult-onset patients at 18 months of hGH, which was within
      the expected prevalence for the number of patients, but was not reported for any
      childhood-onset patients. Only in adult-onset patients were sufficient adverse
      events reported to enable analysis of risk factors. Patients reporting hGH
      related adverse events were significantly heavier and, therefore, received more
      hGH. There was a significantly greater increase in IGF-I and IGFBP-3 in the first
      month in patients who experienced hGH-related adverse events compared with those
      who did not. CONCLUSION: The risks of replacement therapy with hGH in GH
      deficient adults varied with pathogenesis of disease; hGH-related adverse events
      occurred more frequently in patients with adult-onset compared with those
      childhood-onset GH deficiency. In the adult-onset patients there was an increased
      risk of adverse events in heavier patients and those who had the greatest
      increases in IGF-I and IGFBP-3 at 1 month of therapy.

PMID- 9196612
TI  - Urinary IGF and IGF binding protein-3 in children with disordered growth. The
      North West Paediatric Endocrine Group.
AB  - OBJECTIVE: Both IGF-I and IGFBP-3 reflect spontaneous GH secretion in healthy
      individuals. We have evaluated the clinical usefulness of urinary IGF-I and IGFBP
      3 measurements in the diagnosis of children with disordered growth. DESIGN: Serum
      IGF-I and IGFBP-3 radioimmunoassays (RIA) were developed, and modified for
      quantitation in urine. The relationship between serum and urine levels, and the
      performance of these tests in the diagnosis of GH deficiency (GHD) were examined.
      PATIENTS: Sixty-nine children (age 9.5 +/- 3.6 years; 37 boys, 32 girls) provided
      a timed overnight urine collection and a serum sample collected on the same
      morning. Subjects were defined as GHD (n = 22) or short normal (SN; n = 47) on
      the basis of medical history, clinical examination, auxology and peak response to
      a GH stimulation test (< 20 mU/L in GHD patients). MEASUREMENTS: IGF-I and IGFBP
      3 in serum and urine were measured by RIA, urinary GH (uGH) by immunoradiometric
      assay (IRMA) after dialysis and urinary creatinine by the alkaline picrate
      method. Urine results were expressed as total amount excreted (tulGFBP-3
      (microgram), tulGF-1 (ng), tuGH (ng), tuCrt (mmol). RESULTS: Urine IGF-I and
      IGFBP-3 excretion correlated significantly to serum levels of IGF-I and IGFBP-3
      and also to tuGH excretion. There was a strong positive relationship between both
      urinary peptides and tuCrt, which suggested that renal filtration was the source
      of these peptides in urine. In addition, there were significant correlations with
      age, bone age and height SD score, of similar magnitude to those for tuGH. In
      prepubertal children, serum IGF-I and IGFBP-3 were significantly lower in GHD
      compared with SN children, while in puberty only serum IGFBP-3 was significantly
      lower in GHD. There was no difference however, in tulGF-I or tulGFBP-3 between
      GHD and SN children either prepubertally or in puberty with near complete overlap
      of the values between groups. CONCLUSIONS: Measurements of tulGF-I and tulGFBP-3
      have no place in the diagnosis of childhood GHD. Nonetheless, the significant
      correlations between serum and urinary IGF-I and IGFBP-3 levels and their
      correlation to uGH indicate that these peptides could be used as non-invasive
      physiological markers of the GH-IGF axis.

PMID- 9196613
TI  - Thyroid volume and function after 131I treatment of diffuse non-toxic goitre.
AB  - OBJECTIVE: Traditional treatment of diffuse non-toxic goitre are thyroid hormone
      suppression or surgery. When treating nodular non-toxic goitre with 131I
      treatment a reduction in thyroid volume to about 50% has been observed. In the
      present study we evaluated the effect of 131I treatment of diffuse non-toxic
      goitre. DESIGN: Retrospective study of patients treated for a diffuse non-toxic
      goitre and followed by evaluation of thyroid volume measured by ultrasound.
      PATIENTS: Ten selected patients from our out-patient clinic with diffuse non
      toxic goitre. MEASUREMENTS: Thyroid volume was measured by ultrasound and thyroid
      function by serum values of T4, T3, T3 uptake ratio, TSH, TSH receptor antibodies
      and thyroid peroxidase antibodies (anti-TPO). Measurements were performed before
      and 1, 3, 6 and 12 months (and 18 months (n = 7), thyroid volume measured in six
      patients)) after 131I treatment. RESULTS: Thyroid volume declined in all patients
      from median 41 (range 27-160) ml to 20 (range 9-108) ml over 1 year, a reduction
      of 47%. One patient developed transient and one persistent hypothyroidism in the
      follow-up period. Both had elevated anti-TPO levels before treatment (331 and
      9185 U/ml) and demonstrated titre increases of 2.5 and 30 times after 3 and 6
      months, respectively. Pretreatment values were reached after 1 year. The other
      eight patients had normal anti-TPO levels and free T4 and T3 indices did not
      change during follow-up, whereas serum TSH levels demonstrated upward trends
      within the normal range (P < 0.05). TSH receptor antibodies were normal and
      remained so in all patients. CONCLUSIONS: 131I treatment of diffuse non-toxic
      goitre reduces thyroid volume by approximately 50% within 12-18 months.
      Hypothyroidism, during a limited follow-up period, developed only in patients
      with positive anti-TPO levels before treatment.

PMID- 9196615
TI  - Interleukin-6 secreting phaeochromocytoma associated with clinical markers of
      inflammation.
AB  - Phaeochromocytomas have been shown to produce not only catecholamines but other
      neuropeptides and hormones, with a variety of clinical manifestations. We report
      a 70-year-old female patient with phaeochromocytoma exhibiting sustained
      hypertension, low-grade fever, thrombocytosis, and elevated levels of plasma
      fibrinogen and C-reactive protein. Serum interleukin (IL)-6 levels were
      significantly elevated, whereas serum IL-1 alpha and IL-1 beta were not
      detectable. After surgical removal of the tumour, hypertension and low-grade
      fever disappeared, and the laboratory finding including serum IL-6 concentrations
      became normal. Immunohistochemical study of the tumour showed positive staining
      for IL-6. Culture of the resected tumour revealed the production of large amounts
      of IL-6. It is suggested that IL-6 secreted by the tumour was responsible for
      some of the clinical manifestations in this patient.

PMID- 9196614
TI  - Correlation of clinical, endocrine and molecular abnormalities with in vivo
      responses to high-dose testosterone in patients with partial androgen
      insensitivity syndrome.
AB  - OBJECTIVE: To investigate the responses of two patients previously diagnosed as
      Reifenstein's syndrome to graded high-dose testosterone in terms of hormone
      levels, nitrogen balance and sebum secretion and to attempt to correlate these
      parameters with the properties of their androgen receptors and mutations in the
      androgen receptor gene. DESIGN: Nitrogen balance was determined by comparing
      controlled nitrogen intake to the amount excreted. Sebum excretion was measured
      on the forehead. Patients were studied during control periods (no treatment) and
      during administration of testosterone propionate. Blood samples were used as a
      source of genomic DNA and to measure peripheral hormone levels; androgen receptor
      binding was determined using genital skin fibroblasts. PATIENTS: Two patients of
      XY karyotype, with ambiguous external genitalia and problems of testicular
      descent who had required mastectomy as teenagers. Normal male controls of proven
      fertility. MEASUREMENTS: Nitrogen balance, sebum excretion rate and peripheral
      hormone levels (testosterone, dihydrotestosterone, LH and FSH) were studied
      before and after testosterone therapy (1 or 5 mg/kg/day). Genomic DNA was
      extracted from peripheral blood leucocytes and regions of the androgen receptor
      gene amplified by polymerase chain reaction using pairs of specific primers.
      Mobility of amplified DNA from patients was analysed on denaturing gradient
      acrylamide gels and fragments differing in mobility from those of normal controls
      were sequenced. Fibroblasts were cultured from scrotal skin biopsies and androgen
      receptor binding parameters, subcellular localization and up-regulation were
      determined. RESULTS: Testosterone therapy resulted in raised plasma testosterone,
      dihydrotestosterone and oestradiol in both patients. In patient 1 (lesser genital
      abnormality), LH was suppressed by 5 mg/kg/day testosterone to the upper limit of
      the normal range but FSH remained low normal. Both LH and FSH were suppressed by
      testosterone treatment in patient 2 (greater genital abnormality). Nitrogen
      retention was increased in both patients (4.2 and 3.0 g/24 h respectively); sebum
      excretion rate increased to normal in patient 1 but showed no change in patient
      2. Mutations in the androgen receptor gene were identified in both patients. In
      patient 1 a single nucleotide change from adenosine to guanosine resulted in the
      substitution of glycine for glutamic acid at position 772 within the hormone
      binding domain of the receptor. In patient 2 a single nucleotide mutation from
      guanosine to adenosine resulted in the substitution of lysine for arginine at
      position 608 (exon 3) situated in the second zinc finger of the DNA binding
      domain. Both patients had a normal number of androgen binding sites in genital
      skin fibroblasts but those in patient 1 showed reduced binding affinity and rapid
      dissociation of receptor/ligand complexes while those in patient 2 showed
      defective nuclear localization. CONCLUSION: In patients with partial androgen
      insensitivity syndrome the type of androgen receptor mutation and responses to
      short-term androgen treatment can be correlated with the individual's potential
      to virilize. If there is a mutation in the androgen receptor DNA binding domain
      the patient may show little ability to virilize either spontaneously at puberty
      or after androgen treatment. Sebum excretion appears to be more discriminating
      than nitrogen balance or gonadotrophin suppression as an index of tissue response
      to androgens.

PMID- 9196617
TI  - Intracardiac metastases from neuroendocrine tumours.
AB  - We report three cases of intra-cardiac metastases from neuroendocrine tumours of
      the carcinoid type. One presented in a manner identical to a left atrial myxoma;
      in one patient a left atrial mass was noted during investigations for weight loss
      and a lung mass; and in the third, two right ventricular deposits were detected
      on echocardiography when a patient with a disseminated GHRH-secreting tumour was
      investigated for dyspnoea. Although to our knowledge this is only the third
      report of these lesions, we believe that this represents a form of carcinoid
      heart disease that is distinct from the valvular abnormalities seen in some
      patients with carcinoid syndrome. Neuroendocrine metastases should be considered
      in the differential diagnosis of intra-cardiac tumours.

PMID- 9196616
TI  - Cystic glucagonoma with loss of heterozygosity on chromosome 11 in multiple
      endocrine neoplasia type 1.
AB  - A 52-year-old man with a past history of a pituitary adenoma and
      hyperparathyroidism due to a parathyroid adenoma was admitted because of a
      solitary tumour of the pancreas revealed by ultrasonography. His family history
      was unremarkable. Plasma glucagon levels were slightly elevated (280 ng/l, normal
      range, 40-180 ng/l) with decreased plasma amino acid levels. Plasma glucagon
      levels disclosed an exaggerated response during an arginine infusion test and
      paradoxical elevation during a 75 g oral glucose tolerance test. Endoscopic
      ultrasonography revealed a monolocular cystic mass of about 3 cm in diameter in
      the body of the pancreas. A pancreatic tumour was diagnosed before surgery as a
      cystic glucagonoma. Intra-operative ultrasonography showed one cystic mass in the
      body of pancreas and two other solid tumours, about 1 cm and 0.5 cm in diameter,
      in the tail of the pancreas. Histologically, all three tumours showed neoplastic
      epithelial cells with round nuclei forming cords and/or a ribbon-like
      arrangement. They showed positive staining for Grimelius' silver stain and
      immunopositive cells for glucagon. Genetic analysis of the main cystic tumour
      revealed loss of heterozygosity (LOH) on chromosome 11. After the operation, the
      responses of plasma glucagon to arginine infusion and oral glucose became normal.
      Here we describe the usefulness of these provocation tests for early diagnosis
      and post-operative follow-up in a rare cystic glucagonoma associated with
      multiple endocrine neoplasia type 1 (MEN 1) which had LOH on chromosome 11.

PMID- 9196618
TI  - The diagnostic management of suspected scaphoid fracture.
AB  - The role of radiography and bone scintigraphy in the diagnostic management of
      patients with clinically suspected scaphoid fracture after carpal injury is
      reviewed. Evidence is provided that bone scintigraphy is indicated in patients
      with negative initial scaphoid radiographs. A normal bone scan excludes scaphoid
      fracture, and a positive bone scan sufficiently confirms the presence of
      clinically relevant scaphoid fracture. Furthermore, this review assesses the
      possibility on non-invasive additional radiographs, for the diagnosis or
      exclusion on scaphoid fracture as a means of avoiding bone scintigraphy in
      patients with negative first-day X-series.

PMID- 9196619
TI  - Heterotopic ossification: a comparison between reamed and unreamed femoral
      nailing.
AB  - Heterotopic ossification in the abductor region of the hip following reamed
      intramedullary femoral nailing has an incidence as high as 68 per cent. A
      definitive triggering factor for heterotopic ossification remains obscure, but it
      has been suggested that there may be both local and systemic influences. Previous
      work has only been able to show a statistical correlation with systemic factors.
      Sixty antegrade femoral nailings were performed in 58 patients, of which 32 were
      unreamed. There was no significant difference between the two groups for systemic
      risk factors known to have statistical correlation with the formation of
      heterotopic bone. The incidence of heterotopic ossification in the reamed nail
      group was 35.7 per cent and 9.4 per cent in the unreamed nail group (P = 0.01).
      The difference in the incidence of heterotopic bone formation seems to be due to
      local factors, in particular the generation of osteogenic reaming debris, which
      are important in the pathophysiology of heterotopic ossification seen in femoral
      intramedullary nailing.

PMID- 9196620
TI  - Reamed against unreamed nailing of the femoral diaphysis: a retrospective study
      of healing time.
AB  - In order to assess the results of the AO unreamed femoral nail (URFN), and
      specifically its effects on healing, 147 consecutive patients treated were
      reviewed. These included 50 reamed femoral nails (RFN) and 97 unreamed femoral
      nails. Exclusion of pathological fractures, revisions and fractures outside the
      femoral diaphysis left 51 procedures in which the healing process could be
      studied. Twenty-four unreamed and 27 reamed femoral nails in patients with
      diaphyseal fractures AO (32) were followed up by clinical review and
      radiographically until union or death. There were two deaths from multiple
      injuries (one in each group) and two non-unions (at 52 weeks), one in each group.
      There were no cases of infection, angular deformity of leg length discrepancy;
      two cases required early rotational correction. There was a single broken distal
      locking screw in the URFN group but no other implant failures. The fractures in
      the URFN cases took longer to heal with a mean of 26.9 weeks as opposed to 20.5
      weeks in the RFN group (P = 0.009). This did not cause a significant clinical
      problem. The URFN proved easy to use with a much shorter operation time.

PMID- 9196621
TI  - Variability of short arm cast application: the influence of experience using
      fibreglass tape and QuickCast.
AB  - A new short arm cast material which is heated to conform to the underlying limb
      was compared to conventional fibreglass tape. The time required for application,
      the pressures generated beneath the casts and the availability for digital motion
      were studied in three groups with varying lengths of casting experience. Results
      showed that the new immobilizer did not require additional time for application
      and provided similar interface pressures beneath the casts as compared to
      fibreglass tape. In addition, metacarpophalangeal joint motion was less
      restricted with the new casting experience. The shrinkable immobilizer thus
      offers an alternative to conventional fibreglass tape casts.

PMID- 9196622
TI  - Injuries from hovercraft racing.
AB  - A 31-year-old man presented with a potentially serious neck injury following a
      racing hovercraft accident. Previous reports of hovercrafting injuries could not
      be found, and a review of the sport's own records was undertaken. This shows
      there to be a wide range of injuries sustained from the sport, although most of
      them are minor. However, there are some worrying trends, and further studies are
      being undertaking in order to improve the sport's safety record.

PMID- 9196623
TI  - Evaluation of a simple and low-cost external fixator.
AB  - Simple external fixation is becoming ever more popular for the treatment of
      fractures. Current commercially available external fixation devices are complex
      and expensive, affecting management of injuries in less developed countries. In
      this study, a new simple and low-cost external fixator called the AG (Alinoor
      Goh) fixator, is evaluated biomechanically by direct comparison with a
      commercially available fixator device (AO). Four modes of loading were applied to
      each of the fixators: axial compression, anterior-posterior bending, medial
      lateral bending, and torsion. The loads were applied directly onto a fractured
      bone model made of perspex, which was immobilized by the fixator through six
      Schanz pins. From this, stiffness values were obtained by plotting load versus
      displacement. The results from the mechanical testing indicated that in axial
      compression the AG fixator stiffness was 55.7 +/- 0.197 N/mm (AO fixator was 57.7
      +/- 0.186 N/mm); for anterior-posterior bending it was 56.8 +/- 0.153 N/mm (57.4
      +/- 0.134 N/mm); for medial-lateral bending it was 11.4 +/- 0.036 N/mm (11.6 +/-
      0.053 N/mm); and for torsion it was 1.16 +/- 0.002 N.mm/degree (1.16+/- 0.003
      N.mm/degree). No significant difference was found in the stiffness of AG and AO
      fixators, under all modes of loading. A further comparison in terms of overall
      design, versatility in application and cost shows the AG fixator to be a viable,
      inexpensive option for the treatment of long-bone fractures.

PMID- 9196624
TI  - Surgical management of fractures of the acetabulum: the Sheffield experience 1976
      1994.
AB  - Of 56 acetabular fractures treated in Sheffield between 1976 and 1994, 43
      fractures in 40 patients underwent open reduction and internal fixation. This
      paper reviews the surgically managed fractures with emphasis on the quality of
      operative reduction and outcome, in particular the development of degenerative
      osteoarthritis leading to total hip replacement. A good clinical result following
      operative management was seen to correlate closely with a near perfect reduction;
      in contrast, all cases with a poor reduction underwent joint replacement in the
      follow-up period. The relatively few cases managed at a major referral centre in
      this series suggest that either the incidence of acetabular fracture is low in
      the area or that only a proportion of cases are referred from the surrounding
      district general hospitals.

PMID- 9196625
TI  - Ketamine in the field: the use of ketamine for induction of anaesthesia before
      intubation in injured patients in the field.
AB  - Intubating the subconscious, struggling patient in a pre-hospital setting can be
      a difficult task even in experienced hands. We performed a clinical prospective
      study to evaluate the applicability of ketamine for induction of anaesthesia
      before intubation in the field. Ketamine was distributed to all air medical
      rescue teams--trained reserve army volunteers from various medical specialties.
      Lectures and literature concerning the use of ketamine for anaesthesia induction
      before intubation were given. The physicians were instructed to administer
      ketamine, in a dose of 2 mg/kg intravenously, if a single intubation attempt
      failed. Following the administration of ketamine, a questionnaire was filled in
      by the physician. Analysis of the data was performed after 24 months. During the
      study period, intubation was indicated in 161 injured patients evacuated by air
      in Israel. In 29 patients (18 per cent) the first intubation attempt had failed
      and they were given ketamine. The reasons for failure of the first intubation
      attempt were restlessness or trismus in 23 patients and traumatic distortion of
      the upper airway anatomical landmarks in six. Following ketamine administration,
      intubation was successful in 19 patients (65.5 per cent) in all of whom the
      indication for ketamine administration was restlessness or trismus. All patients
      with upper airway anatomy distortion were given a cricothyroidotomy. There were
      no complications attributed to ketamine. All patients reached hospital alive.
      This preliminary study suggests that the use of ketamine in this pre-hospital
      setting is safe. The drug is effective in cases where the primary reason for
      failure to intubate is restlessness or trismus. The drug is not effective in
      cases of anatomical damage to the upper airway. In these cases, cricothyroidotomy
      should probably be performed as early as possible.

PMID- 9196626
TI  - Management of 240 cases of penetrating thoracic injuries.
AB  - We present a review of 240 patients with penetrating thoracic injuries seen in a
      period of 10 years at a general university hospital in Lima, Peru. The majority
      of the patients were young males who suffered stab wounds (76.2 per cent). The
      most frequent symptoms were thoracic pain (N = 202) and dyspnoea (N = 138); and
      the commonest physical findings were diminished respiratory sounds (N = 192) and
      tachypnoea (N = 167). Haemopneumothorax (N = 92), haemothorax (N = 81) and
      pneumothorax (N = 59) were the most frequent lesions. Cardiac lesions were
      present in 11 patients. The commonest extrathoracic associated lesions was
      penetrating abdominal injury (N = 43). The majority of the patients only required
      tube thoracostomy as definitive therapy (N = 143). There were 31 thoracotomies
      and 54 laparotomies. The most frequent complications were respiratory (N = 34)
      and neurological (N = 8). Gunshot wounds were more destructive than stab wounds.
      The first group of patients had a longer hospital stay (11.7 and 7.25 days),
      longer time with tube thoracostomy (5.98 and 4.18 days), more injured abdominal
      organs (3.8 and 2.38 organs) and higher mortality (7.01 per cent and 3.82 per
      cent) than the second group. The overall mortality was 4.58 per cent. The
      patients with a cardiac lesion had a higher mortality (27.27 per cent) than those
      who did not (3.49 per cent).

PMID- 9196627
TI  - Blunt cardiac injury: a 10 year institutional review.
AB  - A 10 year review of all blunt cardiac injuries (N = 70) at a single trauma
      institution was conducted. The majority of patients were diagnosed on the basis
      of elevated myocardial band fraction of creatine kinase (CK-MB), ST/T wave
      changes or arrhythmias. The presence of CK-MB elevation was not predictive of
      arrhythmias, cardiac complications, inotrope requirement, or mortality. The
      presence of ECG abnormalities or arrhythmias was also not predictive of inotrope
      requirement or mortality. Cardia complications requiring treatment occurred in 26
      per cent (N = 18) of patients. Patients requiring inotropes (N = 12, 17 per cent)
      had higher Injury Severity Scores (ISS), longer times from injury to emergency,
      and higher mortality rates, than those not requiring them. Patients who died (N =
      10) had a higher ISS, lower Revised Trauma Score, and a more frequent need for
      inotropes. Only three deaths were directly attributable to the cardiac injury.
      Myocardial contusion is an injury often of little clinical importance. Patients
      present with injuries of little or no consequence, severe injuries where the
      diagnosis is readily apparent, or as a confounding variable in a multiply injured
      patient. Early use of transthoracic echocardiography is advocated.

PMID- 9196628
TI  - Penetrating cardiac injuries.

PMID- 9196629
TI  - The arrest fracture.

PMID- 9196630
TI  - Bilateral acetabular fracture as a result of epileptic seizure: a report of two
      cases.

PMID- 9196631
TI  - External strangulation of the small bowel following injury to inguinoscrotal
      hernia.

PMID- 9196632
TI  - Biepicondylar fracture dislocation of a child's elbow.

PMID- 9196633
TI  - Replantation of four severed limbs in one patient.

PMID- 9196634
TI  - A two way view of gender bias in medicine.

PMID- 9196635
TI  - Secular pattern of congenital oesophageal atresia. 1959.

PMID- 9196636
TI  - Secular pattern of congenital oesophageal atresia--George Knox, 1959.

PMID- 9196637
TI  - Cochrane Lecture. All cost effective treatments should be free ... or, how Archie
      Cochrane changed my life!

PMID- 9196638
TI  - Trends in stroke mortality in Greater London and south east England--evidence for
      a cohort effect?
AB  - OBJECTIVE AND SETTING: To examine time trends in stroke mortality in Greater
      London compared with the surrounding South East Region of England. DESIGN: Age
      cohort analysis based on routine mortality data. SUBJECTS: Resident population
      aged 45 years or more. MAIN OUTCOME MEASURE: Age specific stroke mortality rates,
      1951-92. MAIN RESULTS: In 1951, stroke mortality was lower in Greater London than
      the surrounding South East Region in all age bands over 45. It has been declining
      in both areas but the rate of decline has been significantly slower in Greater
      London (p < 0.0001). The differences in rates of decline were such that stroke
      mortality is now higher in Greater London for people under 75. The crossover of
      age specific stroke mortality rates occurred at different periods in different
      age bands and is consistent with a cohort effect, with similar rates in Greater
      London and the surrounding south east for men and women born around 1916-21. This
      cohort effect does not appear to be consistent with past maternal and neonatal
      mortality rates in these areas, nor, within the limitations of the data, with the
      ethnic composition of cohorts. CONCLUSIONS: There seems to be a cohort effect on
      stroke mortality which is not explained by past maternal and neonatal mortality.
      If the decline in stroke mortality continues at its current rate, the Health of
      the Nation stroke target is unlikely to be achieved in Greater London.

PMID- 9196639
TI  - Socioeconomic deprivation, ethnicity, and stroke mortality in Greater London and
      south east England.
AB  - OBJECTIVE AND SETTING: To examine geographical variation in stroke mortality in
      Greater London compared with the surrounding South East Region of England.
      DESIGN: Cross sectional, ecological analysis based on electoral wards. SUBJECTS:
      Resident population aged 45 years or more. MAIN OUTCOME MEASURE: Age specific
      stroke mortality rates in five age bands, 1986-92. MAIN OUTCOME MEASURE: Age
      specific stroke mortality rates in five age bands, 1986-92. MAIN RESULTS: In the
      45-54 years age band, stroke mortality rate ratios (95% confidence intervals)
      relative to the surrounding south east were 2.09 (1.81, 2.4) for Inner London and
      1.31 (1.15, 1.5) for Outer London for men and 1.64 (1.4, 1.93) and 1.13 (0.98,
      1.31) respectively for women. This gradient diminished and reversed with
      increasing age. In the 85+ age band, rate ratios were 0.82 (0.76, 0.89) for Inner
      London and 0.89 (0.84, 0.94) for Outer London for men and 0.8 (0.75, 0.85) and
      0.88 (0.84, 0.92) respectively for women. Carstairs deprivation index and the
      percentages of Afro-Caribbean men and women and Irish born men were significantly
      and positively correlated with stroke mortality at the ward level. The Carstairs
      effect diminished with increasing age. Adjustment for these variables diminished
      or abolished the higher stroke mortality risks in London for younger people but
      had little effect on the lower risks for older Londoners. CONCLUSIONS: Higher
      rates of stroke mortality among middle aged adults in Greater London, compared
      with the surrounding South East Region, are associated with socioeconomic
      deprivation and ethnicity. These factors do not explain the relatively lower
      stroke mortality among older Londoners.

PMID- 9196640
TI  - Stroke mortality--secular and geographic trends: comment on papers by Maheswaran
      and colleagues.

PMID- 9196642
TI  - Lifelong exposures and the potential for stroke prevention: the contribution of
      cigarette smoking, exercise, and body fat.
AB  - STUDY OBJECTIVE: To examine the potential for stroke prevention by avoidance of
      hazards related to lifestyle. Assessment of the lifelong contribution of both
      individual and combined exposures was a particular feature of the study. An
      estimate was sought of the proportion (population attributable risk fraction) of
      strokes likely to be caused by one or a combination of cigarette smoking, lack of
      exercise, and obesity. DESIGN: Case-control study. SETTING: Eleven general
      practices in west Birmingham. PARTICIPANTS: Altogether 125 men and women who had
      just had their first stroke and were aged 35-74 and 198 controls frequency
      matched for age and sex recruited over 24 months during 1988-90. MAIN RESULTS:
      The hazards of cigarette smoking for stroke were confirmed and noted to persist
      for one to two decades after stopping smoking. Cigarette smoking was estimated to
      have caused 49% (95% confidence level 22, 67%) of the strokes in this population
      with roughly equal contributions from current and former smoking. Combinations of
      cigarette smoking (current and former) with lack of exercise or previous obesity
      apparently caused 62% and 72% of the strokes respectively. If cigarette smoking,
      lack of exercise and obesity were all avoided, 79% (32, 94%) of the strokes could
      potentially have been prevented. No stroke patient reported a combination of
      never smoking, taking regular exercise aged 15 to 25, and avoidance of overweight
      (body mass index > 25 kg/m2). CONCLUSIONS: Taken together, the combination of
      cigarette smoking, excessive body fat, and lack of exercise accounted for a major
      proportion of stroke cases in the population studied. It appears that these
      easily identifiable factors related to lifestyle are a major and possibly
      predominant cause of stroke, at least until the age of 75.

PMID- 9196641
TI  - Geographical and social class differentials in stroke mortality--the influence of
      early-life factors: comments on papers by Maheswaran and colleagues.

PMID- 9196643
TI  - Modelling the effects of increased physical activity on coronary heart disease in
      England and Wales.
AB  - OBJECTIVE: To investigate the use of computer models as tools for policy makers
      in evaluating physical activity interventions aimed at reducing deaths from
      coronary heart disease (CHD). DESIGN: The cell-based computer model Prevent,
      adapted to simulate risk factor interventions for an English and Welsh
      population, was used to simulate the effect of two strategies for increasing
      physical activity levels in respect of CHD mortality over 25 years. The first
      strategy involved a 25% increase in the proportion of 15-64 year olds who were
      moderately active, while the second strategy involved a similar increase in the
      proportion who were vigorously active. The effects of focusing on narrower age
      ranges and on people at different initial activity levels were also explored.
      MAIN RESULTS: The simulations showed a small reduction in the CHD death rates-
      less than 0.15% and 0.06% for men and women respectively. The strategies would
      postpone up to 12,100 deaths over 25 years, comparable to the effect of a 2%
      reduction in smoking prevalence. The strategies seemed as if they would be more
      effective if they concentrated on men rather than women, on those over 45 years
      of age as opposed to all or younger age groups, and on the least active members
      of the population rather than those already taking some exercise. CONCLUSION: The
      use of computer modelling for stimulating physical activity strategies has shown
      that concentrating these interventions on older sedentary men will produce the
      greatest health gain, but efforts to encourage smoking cessation may be more
      effective in terms of years of life saved.

PMID- 9196644
TI  - Hazard proximities of childhood cancers in Great Britain from 1953-80.
AB  - STUDY OBJECTIVES: Firstly, to examine relationships between the birth and death
      addresses of children dying from leukaemia and cancer in Great Britain, and the
      sites of potential environmental hazards; and secondly to measure relative case
      densities close to, and at increasing distances from, different hazard types.
      DESIGN: Home address postcodes (PCs) and their map coordinates were identified at
      birth and at death in children who died from leukaemia or cancer. Potentially
      hazardous industrial addresses and PCs were listed from business and other
      directories, and map coordinates obtained from the Central Postcode Directory or
      else located directly on Ordnance Survey (OS) maps. Railway lines and motorways
      were digitised from OS maps. Numbers of deaths (and births) at successive radial
      distances from these hazards were counted and compared with expected numbers. The
      latter were based on a count of all PCs at similar distances. Relative case
      density ratios at successive distances from the hazards were obtained from
      observed and expected numbers, aggregated over similar sites. This was repeated
      for different hazard types and results were tested for evidence of systematic
      centrifugal case density gradients. PARTICIPANTS AND SETTING: All 22,458 children
      dying from leukaemia or cancer aged 0-15 years, in England, Wales, and Scotland,
      between 1953 and 1980. MAIN RESULTS: Relative excesses of leukaemias and of solid
      cancers were found near the following: (1) oil refineries, major oil storage
      installations, railside oil distribution terminals and factories making bitumen
      products; (2) motor car factories, coach builders, and car body repairers; (3)
      major users of petroleum products including manufacturers of solvents, paint
      sprayers, fibreglass fabricators, paint and varnish makers, plastics and
      detergent manufacturers, and galvanisers; (4) users of kilns and furnaces
      including steelworks, power stations, galvanisers, cement makers, brickworks,
      crematoria and aluminium, zinc, and iron/steel foundries; (5) airfields,
      railways, motorways and harbours. The findings for leukaemias and for solid
      cancers were indistinguishable. The hazard proximities of birth addresses were
      stronger than for death addresses. For children who had moved house between birth
      and death, the proximity effect was limited to the birth addresses. CONCLUSIONS:
      Childhood cancers are geographically associated with two main types of industrial
      atmospheric effluent namely: (1) petroleum derived volatiles and (2) kiln and
      furnace smoke and gases, and effluents from internal combustion engines.

PMID- 9196645
TI  - Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in
      Chinese and Europid adults in Newcastle, UK.
AB  - OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose
      tolerance and diabetes), and its relationship to body mass index (BMI) and waist
      hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional
      study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and
      Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK.
      MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI,
      waist circumference, and waist-hip ratio. METHODS: Population based samples of
      Chinese and European adults were recruited. Each subject had a standard WHO oral
      glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and
      610 Europid subjects. The age adjusted prevalences of glucose intolerance in
      Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese
      men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values <
      0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3
      cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v
      0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared
      with Europids. In both Chinese and Europid adults, higher BMI, waist
      circumference, and waist-hip ratio were associated with glucose intolerance.
      CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women,
      despite lower BMIs, is similar to or higher than that in local Europid men and
      women and intermediate between levels found in China and those in Mauritius. It
      is suggested that an increase in mean BMI to the levels in the Europid population
      will be associated with a substantial increase in glucose intolerance in Chinese
      people.

PMID- 9196646
TI  - Deaths from cirrhosis in Poland and Hungary: the impact of different alcohol
      policies during the 1980s.
AB  - OBJECTIVE: To compare patterns of deaths from cirrhosis in Poland and Hungary in
      the context of differing alcohol policies in the 1980s. DESIGN: Cohort analysis
      of deaths from chronic liver disease and cirrhosis between 1959 and 1992 using
      mortality data from the World Health Organization database. RESULTS: The pattern
      of alcohol related mortality in these countries is quite different. In both
      countries, death rates increased in the 1960s and 1970s. In Poland, this increase
      was arrested in 1980 and death rates have levelled out, with the exception of
      those in young females. In Hungary, rates have continued to climb, although the
      rate of increase decreased in the 1980s. This change coincides with the
      introduction of a policy, following the introduction of martial law, to reduce
      alcohol consumption. CONCLUSIONS: The countries of central and eastern Europe
      display many similarities in both political history and measures of health such
      as overall life expectancy. When examined more closely, substantial differences
      emerge. Policy makers must be cautious about adopting global solutions to health
      challenges that fail to take into account national variations.

PMID- 9196647
TI  - Infectious diseases mortality in central Serbia.
AB  - STUDY OBJECTIVE: To determine the influence and the effect of the war in the
      former Yugoslavia and of the United Nations economic sanctions on mortality from
      infectious diseases. DESIGN: This was a descriptive study analysing mortality
      data time series. SETTING: Central Serbia, Yugoslavia. PARTICIPANTS: The
      population of central Serbia was the subject of the study (about six million
      inhabitants). MEASUREMENTS: Mortality rates were standardised directly, using the
      "European population" as the standard. Regression analysis and analysis of
      covariance were undertaken. MAIN RESULTS: During the period 1973-93, mortality
      from infectious diseases showed a decreasing trend. From 1987-90, and infectious
      diseases was significantly higher than expected on the basis of the trend for the
      preceding period (p = 0.020 and p = 0.00). In addition, there was a statistically
      significant departure from the preceding trend (p = 0.036) in men between 1991
      and 1993 (the period of the war and UN sanctions)--the main effect being in
      younger age groups. CONCLUSION: The economic crisis in the former Yugoslavia
      during the 1980s followed by the outbreak of the war and the damaging effects of
      UN economic sanctions had a distinctly adverse effect on mortality from
      infectious diseases.

PMID- 9196648
TI  - Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are
      restrictions on availability justified?
AB  - OBJECTIVE: To investigate the relationship between the availability of
      paracetamol and its use for overdose and suicide. DESIGN: Analysis of routinely
      collected information on time trends for paracetamol suicides, non-fatal
      overdoses, and sales. SETTING: England and Wales and France. RESULTS: There were
      strong correlations between trends in paracetamol sales in the UK and trends in
      non-fatal paracetamol overdose in Oxford between 1976 and 1993 (Spearman's r =
      0.86; 95% confidence interval (CI) 0.54, 0.96) and between paracetamol sales and
      non-fatal overdoses in France between 1974 and 1990 (r = 0.99; 95% CI 0.97,
      1.00). Sales figures were also correlated with paracetamol related suicides in
      both England and Wales, 1983-91 (r = 0.72; 95% CI 0.11, 0.94) and France, 1974-90
      (r = 0.79; 95% CI 0.50, 0.92). Similarly strong relationships were observed
      between trends in non-fatal overdoses and suicide by paracetamol poisoning in
      England and Wales (r = 0.85; 95% CI 0.61, 0.95) and France (r = 0.79; 95% CI
      0.50, 0.92). It is estimated that approximately 32,000 overdoses involving
      paracetamol occur annually in England and Wales. Fatality rates from paracetamol
      overdose were four times as high in England and Wales (0.4%, 95% CI 0.38, 0.46)
      as in France (0.1%, 95% CI 0.06, 0.17). CONCLUSION: Trends towards greater
      availability of paracetamol are paralleled by increases in its use for both non
      fatal overdose and suicide. Paracetamol related morbidity and mortality seem to
      be less frequent in France where the quantity of paracetamol in a single purchase
      is limited. Although not conclusive, these data add to a body of evidence which
      suggests that restrictions in the quantity of paracetamol available as a single
      purchase in the UK may reduce suicide and liver failure related to paracetamol.

PMID- 9196649
TI  - Quantitative estimates of the impact of sensitivity and specificity in
      mammographic screening in Germany.
AB  - STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of
      mammographic screening (in terms of sensitivity and specificity) on the effects
      and costs of nationwide breast cancer screening. DESIGN: Three plausible
      "quality" scenarios for a biennial breast cancer screening programme for women
      aged 50-69 in Germany were analysed in terms of costs and effects using the
      Microsimulation Screening Analysis model on breast cancer screening and the
      natural history of breast cancer. Firstly, sensitivity and specificity in the
      expected situation (or "baseline" scenario) were estimated from a model based
      analysis of empirical data from 35,000 screening examinations in two German pilot
      projects. In the second "high quality" scenario, these properties were based on
      the more favourable diagnostic results from breast cancer screening projects and
      the nationwide programme in The Netherlands. Thirdly, a worst case, "low quality"
      hypothetical scenario with a 25% lower sensitivity than that experienced in The
      Netherlands was analysed. SETTING: The epidemiological and social situation in
      Germany in relation to mass screening for breast cancer. RESULTS: In the
      "baseline" scenario, an 11% reduction in breast cancer mortality was expected in
      the total German female population, ie 2100 breast cancer deaths would be
      prevented per year. It was estimated that the "high quality" scenario, based on
      Dutch experience, would lead to the prevention of an additional 200 deaths per
      year and would also cut the number of false positive biopsy results by half. The
      cost per life year gained varied from Deutsche mark (DM) 15,000 on the "high
      quality" scenario to DM 21,000 in the "low quality" setting. CONCLUSIONS: Up to
      20% of the total costs of a screening programme can be spent on quality
      improvement in order to achieve a substantially higher reduction in mortality and
      reduce undesirable side effects while retaining the same cost effectiveness ratio
      as that estimated from the German data.

PMID- 9196650
TI  - The effect on compliance of a health education leaflet in colorectal cancer
      screening in general practice in central England.
AB  - OBJECTIVE: To raise compliance in a general practice based colorectal cancer
      screening programme by the use of a simple health educational leaflet. DESIGN: A
      randomised controlled trial of the leaflet's effect on completion of faecal
      occult blood tests. The leaflet explained the high frequency of colorectal
      cancer, the principles of screening, and addressed reasons for non-compliance.
      SETTING: The British town of Market Harborough where most of the population are
      registered with a single practice. PARTICIPANTS: These comprised 1571 residents
      aged 61 to 70 years registered with the practice. Residents were invited to
      receive a free faecal occult blood test in a colorectal cancer screening
      programme. Half the population were randomly assigned to receive the educational
      leaflet about screening. RESULTS: Compliance in test and control groups, positive
      rate of stool testing, and pathology detected were measured. Compliance was
      higher in men who received the leaflet in those aged 61 to 65 years (36% v 27%,
      chi2 = 4.0, p < 0.05) and in men aged 66 to 70 years (39% v 23%, chi2 = 9.7, p <
      0.01). In women, use of the leaflet did not affect compliance in those aged
      either 61 to 65 years (38% v 36%, chi2 = 0.1, NS) or 66 to 70 years (31% v 31%,
      chi2 = 0.0, NS). The positive rate of stool testing in patients observing the
      required dietary restrictions was 1.6%. A significant lesion was detected in 1.4%
      of people tested (2 carcinomas and 5 patients with adenomatous polyps).
      CONCLUSIONS: Health education leaflets addressing reasons for non-compliance
      significantly increased compliance in men and should be used in screening
      programmes. Reasons for the lack of success of the leaflet in women should be
      investigated and other interventions for raising compliance should be developed.

PMID- 9196652
TI  - Effects of preventive health services on survival of the elderly living in a
      community in Osaka, Japan.
AB  - STUDY OBJECTIVE: To examine the relationships between the use of preventive
      health services--such as health checks, basic health examination/cancer
      screening, and daily preventive health practices--and survival of elderly people
      living in the community. DESIGN AND SETTING: A cohort of elderly people aged 65
      years and over living in Settsu City, Osaka was followed for 38 months. Data on
      the history of health management, disability scores, and psychosocial conditions
      were collected in October 1992 by interview during home visits. SUBJECTS: Of the
      1491 people randomly selected from the computerised sex-age register at
      enrollment, 1473 were contacted and responses were obtained from 1405 (95.4%).
      They constituted the study cohort. Follow up was completed for 1325 (94.3%) (154
      decreased and 1171 alive). MEASUREMENTS AND MAIN RESULTS: From the analysis using
      the Kaplan-Meier method and the log-rank test, female sex, younger age group (65
      74 years), use of health checks, use of basic health examination and/or cancer
      screening, use of daily preventive health practices, less disability, taking part
      in social activity, and finding life worth living were univariately statistically
      significantly related to survival. The estimated survival rates were highest in
      those with regular health checks or daily preventive health practices before 59
      years of age or both basic health examination and cancer screening. From the Cox
      proportional hazards model, use of health checks and use of daily preventive
      health practices remained as statistically significant factors associated with
      survival, controlling for other factors such as sex, age group, medical
      treatment, disability scores, and psycho-social conditions, and these hazard
      ratios (not used v starting at 59 years) were 0.41 (95% CI, 0.25, 0.66) and 0.52
      (95% CI, 0.30, 0.88), respectively. CONCLUSIONS: Health management efforts such
      as health checks and daily preventive health practices may increase survival in
      the elderly.

PMID- 9196653
TI  - Trench fever among homeless people in Marseille, France: a seroprevalence survey.

PMID- 9196651
TI  - Predicting the outcome in elderly patients of hospital admission for acute care
      in Paris, France: construction and initial validation of a simplex index.
AB  - OBJECTIVE: To develop a simple index able to identify at an early stage those
      elderly patients at high risk of requiring discharge to a residential or nursing
      home after admission to hospital for acute care. For these patients, early
      discharge planning might lead to a more effective management and reduce the
      length of hospitalisation. DESIGN, SETTING, AND PATIENTS: This was a prospective
      study conducted in two teaching hospitals in Paris, France. A total of 510
      consecutive patients was included. They were aged 75 years or more and had been
      admitted to acute medical care units through the emergency department.
      MEASUREMENTS: Demographic data, social support, physical disability, mental
      disability, and pathologic status were assessed shortly after admission (within
      24-48 hours). MAIN OUTCOME MEASURES: Outcome of hospitalisation was defined as
      discharge to home or residential/nursing home. RESULTS: The index, developed by
      multiple logistic regression, included six variables: the wish of patients'
      principal career about their returning home after acute hospitalisation, presence
      of a chronic condition, ability to perform toileting, ability to know the name of
      the hospital or the city, their age, and their living arrangements. The
      sensitivity of the index in identifying patients at high risk of requiring
      discharge to a residential/nursing home was 74.4%, the specificity 63.8% the
      positive predictive value was 57.8%, and the negative predictive value was 80.6%.
      CONCLUSIONS: The simple index, using data available very early in the course of
      hospitalisation, provides an accurate prediction of the hospitalisation outcome.
      The performance of the index should be tested in other populations and the
      practical benefits of risk screening should be assessed in a controlled trial to
      evaluate whether the intervention is useful and without any adverse effects.

PMID- 9196654
TI  - Accuracy of the family health services authority register in Newcastle upon Tyne,
      UK as a sampling frame for population studies.

PMID- 9196655
TI  - Cigarette smoking and health promotion in Nazi Germany.

PMID- 9196656
TI  - Estimating life expectancy using an age-cohort model: a critique.

PMID- 9196657
TI  - Somatic evolution in the immune system: the need for germinal centers for
      efficient affinity maturation.
AB  - In the course of a humoral immune response, the average affinity of antibody for
      the immunizing antigen can increase in time. This process of affinity maturation
      is due to antigen-driven selection of higher affinity B cell clones and somatic
      hypermutation of the genes that code for the antibody variable region. Through
      the use of simulation models we show that the efficiency of affinity maturation
      is substantially improved if mutation and selection occur in germinal centers,
      specialized regions of lymphoid tissues, rather than in the body as a whole. We
      show that confining mutation and selection to germinal centers decouples the
      problem of affinity maturation from the problem of antigen elimination. In the
      germinal centers, stored antigen, high rates of B cell proliferation and
      apoptosis combine to create an environment where effective maturation occurs even
      after the primary response has eliminated much or all of the free antigen. Kepler
      and Perelson suggested that if hypermutation were turned on and off in a phasic
      manner, affinity maturation could be made more efficient under circumstances when
      affinity-improving mutations have a low probability of occurrence. We confirm
      this in the context of a stochastic model. However, even in the absence of phasic
      mutation, we show that affinity maturation is significantly improved when
      proliferation, mutation, and selection are restricted to germinal centers as
      opposed to occurring systemically.

PMID- 9196658
TI  - Immune network at the edge of chaos.
AB  - Some time ago Jerne proposed a new theory to explain the basis of the immune
      system. He suggested the existence of a functional connected network, based on
      pattern recognition of the idiotypes carried by the lymphocytes, which is
      responsible for the self regulation of the immune system. Only 15-20% of the
      lymphocytes available in the immune repertoire will participate in this
      functional network, while the rest of the lymphocytes will be free to respond to
      any foreign antigen. Each individual immune repertoire will be different
      depending on the lymphocytes that participate in the connected network. Using a
      very simple cellular automata model of the immune repertoire dynamics we show
      that, although the usual regimes (stable and chaotic) attained by this automata,
      are not interesting from the biological point of view, the transition region, at
      the edge of chaos, is very appropriate to describe such dynamics. In this region
      we have obtained a functional connected network involving 10-20% of the
      lymphocytes available in the repertoire, as suggested by Jerne and others. The
      model also reproduces the immune system signature, the ensemble of different
      lymphocytes that each individual expresses in his immune repertoire, which varies
      from one individual to another. We show how the immune memory comes out as a
      consequence of the dynamics of the system. From our results we confirm and
      present evidence that the chaotic regime corresponds to a sort of non-healthy
      state, as has been suggested previously.

PMID- 9196659
TI  - Mathematical model of the SOS response regulation of an excision repair deficient
      mutant of Escherichia coli after ultraviolet light irradiation.
AB  - A mathematical model for the development of the SOS signal in nucleotide-excision
      repair deficient Escherichia coli cells subjected to ultraviolet light
      irradiation is proposed, in which regions of single-stranded DNA (gaps) are
      created during replication of a damaged chromosome when the strand elongation
      stops at pyrimidine dimers. The concentration of single-stranded DNA of gaps as a
      function of time is obtained. The model for the interaction of the LexA and RecA
      proteins, a well-established key event in SOS regulation, is presented, resulting
      in a system of differential equations for the concentrations of LexA, RecA and
      activated RecA proteins. The simulated LexA protein kinetic curves agree with the
      experimental data for two excision repair deficient mutants: uvrA6 and dnaC28
      uvrB(del), which is also a temperature-sensitive DNA replication initiation
      mutant. It is shown that the model can be used to quantitatively describe the
      kinetics of SOS response through the amount of the SOS signal (concentration of
      single-stranded DNA) in a cell as a function of time.

PMID- 9196660
TI  - Vision screening, eye examination and risk assessment of display screen users in
      a large regional teaching hospital.
AB  - In January 1993 the Royal Group of Hospitals Trust, which employs approximately
      5000 staff, implemented the Health and Safety (Display Screen Equipment) Northern
      Ireland Regulations (1992). During 1994 all regular display screen equipment
      users were offered a vision screening test. In total 571 employees were screened
      using computerized vision screening software (City Visual Systems Ltd). Risk
      assessments were completed for 293 display screen work-stations. One hundred and
      twelve full eye examinations, carried out by optometrists, were performed on
      those who failed vision screening and on those who specifically requested an
      optometric assessment. Results indicate that whereas the proportion of users
      experiencing visual and general symptoms differed markedly from department to
      department (28-82%), the median number of individuals failing the screening test
      was 25% (range 9-40%). Those involved in uninterrupted display screen equipment
      work for prolonged periods reported visual and general work-related symptoms
      twice as frequently as those who spent less time working with DSE. The outcome of
      full eye examinations confirmed that less than 5% of display screen users
      required spectacles solely for display screen use. Work-station analysis
      indicated that ergonomic problems were common. The authors conclude that the
      successful management of health risks from display screen equipment requires
      simultaneous attention to work-place design, working patterns and eye care.

PMID- 9196661
TI  - Eye drop container delivery: a source of response variation?
AB  - Variations in response to topically applied ocular drugs (e.g. mydriatics and
      cycloplegics) and their possible aetiology have been studied previously. It
      appears that individual patient differences, external influencing factors and the
      characteristics of the particular drug may all govern the response. One factor
      worthy of note in this regard is the possibility of variation in the drug volume
      instilled. Single-use eye drop containers known as Minims are commonly used
      during ophthalmic diagnostic procedures. However, in this study the drop volume
      was shown to vary considerably, depending upon the angle at which the Minims
      container was held, the particular drug and the number of drops previously
      expelled from the unit.

PMID- 9196662
TI  - Use of contact lenses by firefighters: Part 2. Clinical evaluation.
AB  - Contact lenses can be worn in a variety of environmental conditions and do not
      increase the wearers risk of injury. In many situations they offer significant
      corneal protection. Currently firefighters are prohibited from using contact
      lenses. To evaluate whether contact lenses are a safe form of visual correction
      50 firefighters were fitted, and examined after 1, 4 and 10 months of contact
      lens wear. Twenty-nine were fitted with soft contact lenses, and 21 with rigid
      gas permeable contact lenses. Statistically significant increase in lid sulcus
      hyperaemia was found in both the SCL and RGPCL groups (P < 0.01, P = 0.02,
      respectively), as well as an increase in hyperaemia of the vertical quadrant of
      the bulbar conjunctivae (P = 0.01, P = 0.02, respectively). In addition the RGPCL
      group showed a statistically significant increase in hyperaemia of the lateral
      portion of the bulbar conjunctivae (P < 0.01), consistent with exposure
      epitheliopathy. The SCL group showed statistically significant increase in
      corneal staining in the vertical quadrant for all visits (P = 0.02, P = 0.01, P =
      0.02 for all visits, respectively), indicative of lens dehydration. These
      findings although clinically significant are not unique to firefighting, and are
      found within a "normal" population of contact lens wearers. In conjunction with
      questionnaire data (Owen et all, 1996) we conclude that soft contact lenses can
      be worn safely by firefighters without additional risk.

PMID- 9196663
TI  - Glassblowers' ocular health and safety: optical radiation hazards and eye
      protection assessment.
AB  - The aims of this study were to investigate the levels of optical radiation
      exposure in glassblowing and to determine type(s) of protective eyewear commonly
      used. Radiometric measurements of radiant emissions from different molten glass
      materials and heating systems were carried out in six installations. Spectral
      transmittance curves of available protective lenses used at the locations were
      obtained. Significant variation (P = 0.0001) in ocular irradiation was obtained.
      All operations produced irradiances higher than the threshold limit values (TLVs)
      for the visible spectrum (400 to 700 nm). In craft glassblowing which employs
      furnace systems, irradiance levels exceeding the TLVs for near infrared (760 1o
      1100 nm) were obtained. Molten soda-lime and quartz glasses emitted substantial
      subthreshold near UV radiation. This study shows that variation exists in
      glassblowing ocular radiation exposure due to different glass materials and
      heating systems, therefore selection of appropriate eye protector should be on an
      individual basis.

PMID- 9196664
TI  - Pathway of the primary afferent nerve fibres serving proprioception in monkey
      extraocular muscles.
AB  - Following intracranial section of either the oculomotor or ophthalmic nerve,
      Wallerian degeneration studies revealed 1.38-3.7% of nerve fibres in the nerves
      to the inferior and superior rectus muscles were of ophthalmic nerve origin; more
      than half of them were unmyelinated. The results of the two experiments were
      complementary. The proportion of fibres identified as sensory is substantially
      smaller than the 10%, estimated in other studies, required to serve muscle
      receptors. These results indicate, contrary to some reports, that a substantial
      majority of proprioceptive fibres are conducted from extraocular muscles to the
      brainstem in the motor nerves and that their somata are not housed in the
      trigeminal ganglion.

PMID- 9196665
TI  - Spectral sensitivity in patients with dysthyroid eye disease.
AB  - The majority of patients with dysthyroid eye disease have an acquired colour
      vision defect. However, no psychophysical investigation of selective damage to
      colour or flicker pathways has been carried out. In order to clarify the nature
      of the visual pathology, we have used a psychophysical technique (spectral
      sensitivity) to selectively stimulate the chromatic and achromatic mechanisms.
      Spectral spots of size 1 degree presented at a rate of 1 Hz on a bright 1000 td
      white background are detected by the chromatic mechanism but a rate of 25 Hz
      reveals the achromatic mechanism. Fifteen patients (28 eyes) between the ages of
      50-70 years were tested. The study showed that all patients had reduced spectral
      sensitivity, either 1 Hz, 25 Hz or both. The patients with reduced 1 Hz or 25 Hz
      spectral sensitivity only had a shorter systemic and ocular duration of the
      condition, had no proptosis, normal intraocular pressures in primary gaze,
      slightly higher intraocular pressures on upgaze, normal visual field plots and FM
      100-Hue error scores higher than the normal age-matched values. The patients with
      reduced both 1 Hz and 25 Hz spectral sensitivities had a longer systemic and
      ocular duration of the condition, had proptosis, normal intraocular pressures in
      primary position, higher intraocular pressures on upgaze and higher FM 100-Hue
      error scores than the age-matched normals and those in Groups 1 and 2. A total of
      50% of patients in Group 3 had defective visual field plots. These data suggest
      that there is a damage of the large achromatic fibres and small chromatic fibres
      in dysthyroid eye disease. The mechanism of the damage could be one of ischaemic
      or mechanical or both.

PMID- 9196666
TI  - Quantification of prism induced metamorphopsia as a model for clinical retinal
      (and other) distortions.
AB  - Metamorphopsia (all causes) results in perceived distortions in the visual field.
      A simple technique utilizing hyperacuity judgements was developed in this
      laboratory some years ago to allow quantification of such distortions. We ask
      here, how good is this assessment method at detecting a distortion? To control
      better investigations of metamorphopsia, a model providing constant optical
      distortions and resultant perceptual metamorphopsia was devised using plane
      prisms of 8 delta and 15 delta. The instrument includes a beamsplitter and a CRT
      display controlled by an IBM PC computer and 'mouse'. In this study, three short
      vertical lines (perpendicular to the prism base-apex line) were used to assessed
      image distortion in the central retinal area. Positions of individual lines of
      this pattern were varied in order to determine perceived distortions induced by a
      prism. Normal observers were tested on multiple occasions. It is possible to
      measure accurately prism-induced directional biases (mean locations) using this
      method. We separated personal setting biases from the prism-related distortions.
      The test method devised mimics modest clinical metamorphopsia. Prism magnitude
      affected settings. We were able to make judgements to less than +/- 2% error.

PMID- 9196667
TI  - Clinical use of the American Optical Company (Hardy, Rand and Rittler)
      pseudoisochromatic plates for red-green colour deficiency.
AB  - The efficiency of the American Optical Company (Hardy, Rand and Rittler) (HRR)
      plates for screening, grading and classifying red-green colour deficiency was
      examined for 401 male colour deficient subjects previously identified and
      diagnosed with Nagel anomaloscope. There were 83 protanopes, 30 protanomalous
      trichromats, 96 deuteranopes and 192 deuteranomalous trichromats. Screening
      sensitivity was found to be 100% for dichromats and 96.4% for anomalous
      trichromats based on one screening error (35 subjects, including 7 dichromats,
      where identified by a single error). Thirty subjects (13.5%) made errors on
      screening plates only and were identified as having minimal colour deficiency.
      The HRR grading system did not distinguish dichromats and anomalous trichromats;
      54% of dichromats were graded as having moderate rather than severe colour
      deficiency. Protan/deutan classification was correct for 95% of subjects who
      failed grading plates. HRR grades for anomalous trichromats were compared with
      the anomaloscope matching range and with pass or fail of the D15 test. The
      results show that only two rather than four grading categories can be
      distinguished by the HRR plates and that both the D15 and the HRR plates are
      needed in a vocational test battery to establish the severity of colour
      deficiency.

PMID- 9196668
TI  - Inter-ocular temporal asynchrony (IOTA): psychophysical measurement of inter
      ocular asymmetry of visual latency.
AB  - Ocular pathology can be associated with inter-ocular asymmetry of conduction
      latency. We describe a relatively low-cost psychophysical method of quantifying
      this asymmetry of delay, an 'inter-ocular temporal asynchrony' (IOTA) system.
      Testing of 28 visually normal young adults gave IOTA results with a mean of 0.11
      ms (SD +/- 2.4 ms). These results correspond to 95% confidence limits of -4.6 ms
      and +4.8 ms. Inter-ocular differences in retinal illumination, induced by using
      monocular neutral density filters in visually normal subjects, significantly
      affected IOTA in accord with an imposed perceptual delay in the 'filtered eye'.
      This demonstration that the IOTA technique is capable of detecting induced
      asymmetry of perceptual delay in visually normal subjects, along with the small
      measured confidence limits reported above, suggests that the apparatus should be
      capable of detecting inter-ocular asymmetries in response latencies with ocular
      disease, which have been previously measured by other techniques.

PMID- 9196669
TI  - Gold plating on spectacle frames.
AB  - An investigation was carried out into the thickness and standard of application
      of the plating and lacquer coatings applied to three metal spectacle frames. All
      conform to BS 6625 (1991) for plating thickness, but there was considerable
      variation in regularity and porosity.

PMID- 9196670
TI  - Standard criterion for fluctuations of modulation transfer function in the human
      eye: application to disposable contact lenses.
AB  - It is well known that the modulation transfer function (MTF) characterizes the
      optical quality of the eye. Recently, some objective techniques have been
      introduced in order to measure this function in vivo. These techniques could be
      employed to display the temporal fluctuations of the eye + compensation system
      and to isolate the effect of the compensation element provided that the standard
      fluctuations for a normal observer were known. In this work we carry out a study
      of the MTF of the human eye over a long period of time to quantify the standard
      fluctuations of the retinal image quality and to establish a standard criterion
      of normality. We have defined a single quality parameter from each measured MTF
      to simplify the analysis of the results. We have evaluated this merit function on
      normal observers three times a day for one month. As expected, random deviations
      from the mean value of the merit function have been obtained, although
      fluctuations with no statistical differences of the merit function (P value from
      ANOVA test P > 0.01) and the standard deviation of these fluctuations (5%) can be
      chosen as a standard criterion. We have used this result to study the behaviour
      of a time-varying compensation element: a disposable contact lens. The study of
      the eye + contact lens system has been carried out with four types of disposable
      contact lenses for one month. In spite of their generally good behaviour,
      statistically significant differences from the standard pattern can be observed.
      This superimposed continuous fluctuation can be due to lens-dependent processes.

PMID- 9196671
TI  - Does hyperglycaemia have an influence upon colour vision of patients with
      diabetes mellitus?
AB  - It has been suggested that variations found in colour vision upon repeated
      testing may be due to fluctuations in the plasma glucose level, but the results
      of studies to date are conflicting. Therefore, the aim of this study was to
      investigate whether a short-term increase in plasma glucose concentration had an
      influence on colour vision in patients with non insulin-dependent diabetes
      mellitus (NIDDM) (n = 16). The colour vision and plasma glucose levels were
      monitored every 30 min for a total period of 4 h during three test conditions:
      two when the plasma glucose levels were increased by the administration of
      glucose, either orally (n = 8) or intravenously (n = 8), and one when the plasma
      glucose was relatively stable during fasting conditions (n = 8). The results
      indicate that the colour vision, as assessed by the Desaturated D15, appears to
      be unaffected by the short-lived increases in plasma glucose concentrations.

PMID- 9196672
TI  - Use of contact lenses by firefighters. Part 1: Questionnaire data.
AB  - The use of contact lenses by firefighters is currently prohibited. However, many
      firefighters may benefit from this form of visual correction, without
      predisposing themselves to additional risk. Visual benefits gained by contact
      lens wear may increase a firefighter's safety. To determine if it is safe to
      allow firefighters to use contact lenses 29 were fitted with soft contact lenses
      and 21 with rigid gas permeable contact lenses. Questionnaires were completed
      prior to fitting, after 1, 4 and 10 months of contact lens wear. Both soft
      contact lens (SCL) wearers, and rigid gas permeable contact lens (RGPCL) wearers
      showed a statistically significantly reduction in the frequency with which they
      experience irritable foreign bodies and irritant fumes in the eyes, compared to
      not wearing contact lenses. Firefighters felt that their performance on the
      fireground had been improved by the use of contact lenses. SCL wearers also
      benefited from a reduction in the frequency with which they experienced watery
      eyes and ocular discomfort. There were significantly fewer problems encountered
      with SCL wearers than RGPCL wearers. The frequency with which firefighters
      experienced lenses falling out, lens displacement, watery eyes, ocular
      discomfort, and operational difficulties was significantly less for the SCL group
      than the RGPCL group. SCL appear to offer considerable benefits for firefighters
      with refractive error, but their use cannot be sanctioned without assessment of
      their effect on the ocular adnexa.

PMID- 9196673
TI  - The effect of accommodative hysteresis on apparent stationarity.
AB  - The potential contribution of accommodation to the ability to perceive whether an
      object is moving in space during lateral movement of the head was examined in 16
      visually-normal young adults. The target, which provided a highly effective
      accommodation stimulus, was viewed monocularly in an otherwise completely
      darkened room. Self-generated head movements of controlled amplitude and
      frequency were used to produce lateral target motion of continuously variable
      amplitude either in-phase or counter-phase to the lateral translation of the
      head. Tonic accommodation and the target/head displacement ratio needed for
      apparent target stationarity were measured before and after sustained focus at
      either the nearpoint or farpoint. Tonic accommodation shifted inward under the
      nearpoint condition and outward under the farpoint condition. The tonic
      aftereffects induced under the nearpoint and farpoint conditions were accompanied
      by increases and decreases, respectively, in the degree of positive (same
      direction as the head) concomitant motion required for apparent target
      stationarity. These results suggest that the altered accommodative effort
      required to compensate for the tonic aftereffects influenced the magnitude of the
      absolute visual parallax ascribed to self-motion. The accommodative system
      therefore appears to contribute to position constancy, at least in a relatively
      impoverished visual environment.

PMID- 9196674
TI  - Non-stereoscopic cues in the Random-Dot E stereotest: results for adult
      observers.
AB  - The purpose of this study was to investigate performance on the Random-Dot E
      (RDE) stereotest under binocular and monocular non-stereoscopic viewing
      conditions. Sixteen adult observers with normal vision were tested with the RDE
      stereotest. Four new RDE tests were shown to each observer in varying
      combinations of monocular viewing, binocular but non-stereoscopic viewing, and
      normal binocular viewing conditions. The test conditions were masked (where
      possible) and were presented in pseudo-random order. Control experiments were
      also conducted using the Frisby stereotest. Fifteen of the sixteen observers
      could discern some differences between the plates monocularly and therefore
      satisfied the passing criterion of the RDE test. Under these conditions, no
      observers could discern the stereoscopic E figure nor did any observer report a
      sensation of depth. No observer satisfied the passing criterion of the Frisby
      test monocularly. We conclude that caution should be used when interpreting
      results from the RDE stereotest, since adult observers could discern some
      differences between the test plates monocularly.

PMID- 9196675
TI  - The effect of defocus on edge contrast sensitivity.
AB  - The effect of optical blur (defocus) on edge contrast sensitivity was studied.
      Edge contrast sensitivity detoriates with fairly small amounts of blur
      (approximately 0.5 D) and is roughly reduced by half for each dioptre of blur.
      The effect of blur on edge contrast sensitivity equals the effect of blur on sine
      wave contrast sensitivity for a spatial frequency of approximately 3 cpd.

PMID- 9196676
TI  - A model of inhomogeneous expansion of the cornea and stability of its focus.
AB  - A simple derivation of an analytical condition for expanding the cornea to get
      the stable position of the corneal focus is given. The corneal thickness
      increases from the apex till the limbus and the corneal shell expands
      inhomogeneously as a result of changes in intraocular pressure conditions. It
      expands more in the centre of the cornea and less at its apex. As a result the
      expansion changes the paraxial radius of the corneal curvature by the value of
      delta r as well as displaces the position of the centre of the central corneal
      curvature by the value of s. Presented paraxial calculations show that the
      position of the corneal focus is stable and insensitive on the expansion of the
      cornea if the ratio of both values amounts to about 0.34. Comparison of
      analytical results with published results of experiments on expanding intact
      cornea in vitro indicates their high accordance. This suggests a new, important
      role of the thickness distribution of the cornea.

PMID- 9196677
TI  - A prospective study of the effect of education on non-compliant behaviour in
      contact lens wear.
AB  - The contact lens practitioner and patient present a specific case for the study
      of non-compliance in areas such as hygiene, solution use, appointment attendance
      and wearing times. Education is one of the factors thought to influence
      compliance among patients in general health care situations and contact lens
      practitioners are encouraged to educate patients in the care and maintenance of
      contact lenses. A prospective, randomized, controlled and double masked study was
      performed to assess the effect of a 'compliance enhancement strategy' on levels
      of compliance among contact lens wearers over twelve months. Eighty experienced
      contact lens patients were randomly allocated to two experimental groups. A
      standard level of contact lens instruction was applied to the first group and in
      addition the compliance enhancement strategy was applied to patients assigned to
      the second group. The strategy consisted of extra education for patients using a
      video, booklets, posters, a checklist and a health care contract. Patients were
      given free supplies of ReNu multipurpose solution and Medalist 38 soft contact
      lenses (Bausch and Lomb, Rochester, New York). Compliance levels were assessed at
      a twelve month aftercare appointment by demonstration and questionnaire. The
      results indicate that the compliance enhancement strategy had little significant
      effect on the compliance levels of the patients to who it was applied. The
      population of contact lens wearers were generally very compliant and the contact
      lenses and care regimen were clinically successful. The possibility that the
      assessment of non-compliance was not adequately sensitive to highlight small
      differences in non-compliant behaviour is discussed. The standard level of
      education applied to this sample of contact lens patient were adequate to ensure
      generally high levels of compliance with the simple care and maintenance regimen
      recommended.

PMID- 9196678
TI  - The variation in the threads of the dowel screws of spectacle frames.
AB  - British Standards specify a very small number of screw sizes as being acceptable
      for use in spectacle frames. We have measured the screw sizes of 50 frames,
      selected at random from the stock of Glasgow Caledonian University Clinic and
      have shown that very few of the screws used conform to these standards.

PMID- 9196679
TI  - A method for increasing the scoring efficiency of the Farnsworth-Munsell 100-Hue
      test.
AB  - This paper describes a method for scoring the Farnsworth-Munsell 100-Hue test,
      based on maximum-likelihood estimation, which in theory reduces test-to-test
      variability in scores and which is therefore better able to discriminate between
      different levels of overall colour discrimination than is the original Farnsworth
      scoring system. Error scores produced by the method are directly comparable to
      error scores produced by the traditional scoring system. It is hoped that this
      work will provoke further consideration of the efficiency of the scoring system
      as far as test-to-test variability is concerned, including the efficient
      detection of polarity in the subject's hue discrimination function.

PMID- 9196680
TI  - Design of an Arabic near visual acuity chart.
AB  - This paper describes the design of an Arabic test chart for measurement of visual
      acuity at near. The chart was designed employing specially selected Arabic
      letters and was based on the logMAR principle devised by Bailey and Lovie. Ten
      Arabic letters of nearly equal legibility values (0.92-1.05) (mean = 1.00), (SD =
      0.05) were used in the design of the chart. Each row of the chart has 5 letters
      and row legibility values range from 4.82 to 5.03 with a mean of 4.92 (SD =
      0.06). The logMAR method of visual acuity scaling was used, hence the sizes of
      letters in the rows progress in a uniform step of 0.1 log unit. The inter-letter
      spacing is equal to the width of each letter in the row, while inter-row spacing
      is equal to the height of letter in the subjacent row. The height of letters
      ranged from 3.67 to 0.46 mm corresponding to visual acuity of 2.4 M to 0.3 M
      which is equivalent to reduced Snellen 6/36 to 6/4.5 at 0.4 m. The chart is
      designed for use at 40 cm with a recommended luminance level of 160 cd/m2.

PMID- 9196681
TI  - Ronchi test for testing the powers of bifocal intraocular lenses.
AB  - The Ronchi test is one of the simplest and most powerful methods for evaluation
      and measuring the spherical aberration of an optical system and is an accurate
      method for measuring the focal length of an IOL (Carretero et al., 1992, 1993).
      The accuracy of lens power specification is a crucial factor for bifocal
      intraocular lenses (IOLs). Therefore, the powers of these IOLs must be tested to
      verify that the lenses have been manufactured according to the design. In this
      paper we suggest the use of the Ronchi test for testing the two powers of bifocal
      IOLs.

PMID- 9196682
TI  - Yves Le Grand and the assessment of retinal acuity using interference fringes.
AB  - Just over sixty years ago, Yves Le Grand's article 'Sur la mesure de l'acuite
      visuelle au moyen de franges d'interference' (C. R. Acad. Sci. Paris 200: 490
      491; 1935) was published. A translation of this important article into English is
      given and a commentary discusses the application of the interference fringe
      method to the study of the ocular modulation transfer function, the spatial
      arrangement of retinal receptors and the potential acuity of cataract patients.

PMID- 9196683
TI  - Determination of crystalline lens radius.

PMID- 9196685
TI  - Vision and action: you ain't seen nothin' yet ...

PMID- 9196684
TI  - Determination of the radius of curvature of the anterior lens surface from the
      Purkinje images.

PMID- 9196686
TI  - Linear motion aftereffect induced by pure relative motion.
AB  - The effect of adaptation to pure relative motion was investigated for the motion
      aftereffect (MAE) of linear translation motion. In experiment 1, MAE induced by
      adaptation in the surrounding area was tested. The relative motion signal
      significantly increased the magnitude of MAE while local MAE in the surrounds was
      not affected. In experiment 2, MAE observed in the same adapted area was examined
      while local adaptation was cancelled out. Substantial MAE was found only when the
      test stimuli included the surroundings, which is considered to be favourable for
      relative motion mechanisms. These results clearly indicate that MAE is induced by
      adaptation to pure relative motion as well as by local motion. MAE should be
      regarded as a composite phenomenon reflecting multiple sites of adaptation
      including the local and the relative motion levels. The results also provide
      evidence for the existence of independent detecting mechanisms for relative
      motion processing.

PMID- 9196687
TI  - Perceived angular and linear size: the role of binocular disparity and visual
      surround.
AB  - An experiment was conducted to investigate the effects of perspective cue and
      binocular disparity on perceived angular and linear size. Following the 'angular'
      and 'linear' instructions, subjects matched the size of two squares, for which
      the binocular disparity between the centers of the squares and the configuration
      of the stimulus surrounding the squares were manipulated. Results showed that
      angular-size matches depended on the retinal-image size and the binocular
      disparity, and not on the visual-surround stimulus. Linear-size matches, on the
      other hand, depended on the visual-surround stimulus as well as on the image size
      and the binocular disparity. The visual-surround stimulus also affects the
      perceived depth between the test squares. These findings indicate that perceived
      angular and linear size depend on different processes that use different cues,
      and suggest that there is a causal relationship between perceived depth and
      perceived linear size.

PMID- 9196688
TI  - Occlusion constraints and stereoscopic slant.
AB  - In binocular vision horizontal magnification of one retinal image leads to a
      percept of three-dimensional slant around a vertical axis. It is demonstrated
      that the perception of slant is diminished when an occlusion interpretation is
      possible. A frontoparallel plane located in the immediate vicinity of a slanted
      surface in a location which allows a perception of occlusion reduces the
      magnitude of perceived slant significantly. When the same plane is placed on the
      other side, the slant perception is normal because there is no alternative
      occlusion interpretation. The results indicate that a common border between the
      occluder and a slanted surface is not a necessary condition for the reduction
      effect. If the edges are displaced and the edge of the slanted surface is placed
      in a location in which it could be occluded, the effect still appears.

PMID- 9196689
TI  - The luminance conditions of transparency.
AB  - In two experiments the luminance conditions for the occurrence of phenomenal
      transparency in achromatic flat patterns was studied. Let a, p, q and b be,
      respectively, the luminances of the parts A, P, Q, and B of a pattern comprising
      a transparent square on a two-part background, where P and Q are the parts of the
      square on backgrounds A and B, respectively. The results showed that magnitude of
      p-a, magnitude of q-b, and magnitude of p-q were quantitative conditions of
      transparency. Metelli has proposed two ordinal conditions of transparency,
      magnitude of a-b > magnitude of p-q and p > q if a > b (or p < q if a < b).
      Alternatively, Masin and Fukuda have proposed the single ordinal condition p
      [symbol: see text] (a, q) [or q [symbol: see text] (p,b)]. The results showed
      that this second condition best predicted the occurrence of transparency.

PMID- 9196690
TI  - Orientation priming of novel shapes in the context of viewpoint-dependent
      recognition.
AB  - Can visual similarity between shapes facilitate orientation priming? Five
      experiments are reported in which this possibility was explored by using novel
      two-dimensional shapes that formed homogeneous stimulus classes. After training
      on individual shapes in a canonical view, the recognition of these shapes was
      tested in several picture-plane orientations. In experiments 1 and 2 an
      identification task was used to replicate the classic finding obtained with the
      mirror-judgment task-that prior orientation cueing does not reduce the magnitude
      of orientation dependence in processing rotated shapes. The results of experiment
      3, however, indicate that blocking trials by orientation is one condition in
      which orientation priming may be obtained. Experiment 4 builds on this result,
      and it is suggested that awareness of the blocking manipulation is not required
      to obtain orientation priming. In experiment 5 the mechanisms underlying this
      finding are explored, and evidence is offered that orientation priming is a
      consequence of representations that encode both shape and orientation. Such
      results may be considered as an extension to the 'image-based' approach to object
      recognition, demonstrating that generalization across exemplars may occur within
      recognition mechanisms that are viewpoint dependent.

PMID- 9196691
TI  - Sex classification is better with three-dimensional head structure than with
      image intensity information.
AB  - The sex of a face is perhaps its most salient features. A principal components
      analysis (PCA) was applied separately to the three-dimensional (3-D) structure
      and graylevel image (GLI) data from laser-scanned human heads. Individual
      components from both analyses captured information related to the sex of the
      face. Notably, single projection coefficients characterized complex differences
      between the 3-D structure of male and female heads and between male and female
      GLI maps. In a series of simulations, the quality of the information available in
      the 3-D head versus GLI data for predicting the sex of the face has been
      compared. The results indicated that the 3-D head data supported more accurate
      sex classification than the GLI data, across a range of PCA-compressed
      (dimensionality-reduced) representations of the heads. This kind of dual face
      representation can give insight into the nature of the information available to
      humans for categorizing and remembering faces.

PMID- 9196692
TI  - The speed of visual search in the absence of sensory effects.
AB  - The purpose of this study was to investigate the efficiency or speed of the
      frequently used L versus T visual search when sensory effects were controlled, ie
      'set size' was not defined as the number of distractor patterns, but the number
      of distractors in the display was kept constant and the number of possible target
      positions varied. A search display consisted of an L-target among T-distractors,
      and the observer's task was to report the presence or absence of the target
      (experiment 1) or to identify it (whether the L-target was left-facing or right
      facing; experiment 2). The observer was instructed prior to each stimulus block,
      about the display locations in which the target could appear. In both
      experiments, search time increased significantly with an increasing number of
      possible target locations, thus indicating that L versus T search is not 'serial'
      owing to sensory effects. Because, in the first two experiments, a search display
      was visible until the observer gave a response, 'serial' search might have
      resulted just from eye movements. Therefore, a control experiment was run in
      which display duration was limited to 150 ms. The results of this experiment
      showed that, even when eye movements were prevented, the search still occurred
      'serially', ie response time increased as a function of the number of possible
      target positions.

PMID- 9196693
TI  - Autistic artists give clues to cognition.
AB  - Certain autistic children whose linguistic ability is virtually nonexistent cart
      draw natural scenes from memory with astonishing accuracy. In particular their
      drawings display convincing perspective. In contrast, normal children of the same
      preschool age group and even untrained adults draw primitive schematics or
      symbols of objects which they can verbally identify. These are usually conceptual
      outlines devoid of detail. It is argued that the difference between autistic
      child artists and normal individuals is that autistic artists make no assumptions
      about what is to be seen in their environment. They have not formed mental
      representations of what is significant and consequently perceive all details as
      equally important. Equivalently, they do not impose visual or linguistic schema-a
      process necessary for rapid conceptualisation in a dynamic existence, especially
      when the information presented to the eye is incomplete.

PMID- 9196694
TI  - Comments on Parks's "Prior experience of form and illusory figures: new
      demonstrations".
AB  - Parks presented two example figures to illustrate that (i) familiarity can
      enhance illusory contour effects by completing an otherwise incomplete form and
      (ii) such contours are enhanced when their presence can explain an otherwise
      familiar but incomplete form. While familiarity probably does enhance illusory
      contours, additional perceptual factors may be involved in Parks's
      demonstrations.

PMID- 9196695
TI  - Investigation into the origin of the haptic aftereffect of curved surfaces.
AB  - In haptics, the perceived (phenomenal) flatness of a surface is strongly
      influenced by a previous surface which has been statically touched. The
      mechanisms underlying this haptic aftereffect of curved surfaces are
      investigated. It is shown that the representation of curvature abstracted from
      the sense of touch, ie a high-level representation, is not affected during the
      aftereffect. This is concluded because: (1) the aftereffect does not exhibit
      intermanual transfer; (2) the way in which two successive surfaces are touched
      can influence the magnitude of the aftereffect; and (3) it is not necessary to
      touch a surface-active muscular contraction can also result in a shift of the
      phenomenal flatness. Furthermore, it is suggested that the physiological process
      involved in the aftereffect is a central process, ie it is located in the brain
      but it is distinct for each hemisphere. This is supported by the findings that:
      (1) the decay rate of the aftereffect is not influenced by the degree of
      peripheral stimulation during the decay; and (2) the aftereffect does not
      transfer from the adapted hand to the unadapted hand.

PMID- 9196696
TI  - Parkinson's disease.
AB  - Parkinson's disease is a common disabling disease of old age. The diagnosis of
      idiopathic Parkinson's disease is based on clinical signs and has poor
      sensitivity, with about 25% of patients confidently diagnosed as having the
      disease actually having other conditions such as multi-system atrophy and other
      parkinsonism-plus syndromes. Benign essential tremor and arteriosclerotic pseudo
      parkinsonism can easily be confused with Parkinson's disease. The cause of
      Parkinson's disease remains unknown. Speculative research highlights the role of
      oxidative stress and free radical mediated damage to dopaminergic cells.
      Parkinson's disease is the one neurodegenerative disorder in which drugs have
      been demonstrated to be of value. There is now a wide variety of drugs and
      formulations available, including anticholinergics, amantidine, L-dopa, dopamine
      agonists including apomorphine, selegiline and soon to be available catechol-O
      methyltransferase inhibitors. Disabling side-effects of treatment, fluctuations,
      dyskinesias and psychiatric problems require strategic use of the drugs
      available. There is an increasing potential for neurosurgical intervention.

PMID- 9196697
TI  - Boerhaave's syndrome.
AB  - Boerhaave's syndrome or spontaneous oesophageal perforation, is a potentially
      lethal and frequently elusive medical condition which presents not only a
      diagnostic but also a therapeutic challenge. It is insufficiently considered in
      diagnostic hypotheses, yet may be confirmed or excluded by simple methods such as
      an erect chest film and a contrast study of the oesophagus. Errors in diagnosis
      are usually caused by unawareness of its varied and atypical presentations or
      failure to consider its possibility in acute cardiothoracic and upper
      gastrointestinal conditions. Early aggressive surgical intervention in the form
      of open and wide mediastinal and chest drainage, with or without oesophageal
      repair, resection or exclusion, offers the patient the best chance of survival
      against this otherwise invariably fatal event. Nonoperative therapy consisting of
      antibiotics, nil oral regimen, nasogastric tube suction, pleural drainage, H2
      receptor blockers and either a feeding enterostomy or total parenteral nutrition,
      may also be appropriate in selected patients. It is probable that the condition
      is more common than is generally supposed. All clinicians need to be aware of
      this lethal disease, its frequently unusual presentations and the importance of
      early diagnosis.

PMID- 9196698
TI  - Genes and the development of vascular disease.
AB  - Clinical vascular disease occurs as the result of the chronic development of
      atherosclerosis, often with acute occlusive thrombus formation as the final
      event. Both atherosclerotic and thrombotic disorders are complex processes
      resulting from genetic and environmental interactions. We review genes currently
      implicated as risk factors and the approaches for identifying novel genetic risk
      factors.

PMID- 9196699
TI  - Learning contracts in higher professional training: a user's guide.
AB  - If the doctor undergoing higher professional training is to make best use of the
      attachment to a training location, and that training location is to make the most
      efficient use of the contribution of the trainee, then a written framework such
      as a learning contract can meet the needs of both. The first stage is to list the
      learning needs of the individual trainee and to match them with the work
      experience offered by the training location. Next, the work programme for the
      coming six to 12 months should be formalised in a learning contract, spelling out
      the tasks to be performed and the expected training benefit. This is then
      reviewed at agreed intervals and a written appraisal made. At the end of the
      attachment the trainee, trainer and any outside accrediting or auditing body, has
      a written account of what was expected, what was achieved, and the performance of
      trainee and trainer.

PMID- 9196700
TI  - Anticoagulants for venous thrombosis.
AB  - The anticoagulant agents heparin and warfarin were introduced before the era of
      randomised clinical trials. As a result, the indications, dosages and monitoring
      techniques of these drugs have undergone re-evaluation in multiple clinical
      trials in the past years. Low molecular weight heparin has been developed, which
      has led to new approaches in anticoagulant management. Current levels of
      laboratory, pharmacology and clinical knowledge in the treatment of venous
      thromboembolism are discussed.

PMID- 9196701
TI  - The prevalence of Addison's disease in Coventry, UK.
AB  - The prevalence of Addison's disease (chronic adrenal failure) has not been widely
      investigated and is usually given as 39 in a million. We conducted a prevalence
      study using a postal survey of general practitioners in Coventry. Three quarters
      (139/188) replied, representing 79/85 (93%) of the practices. Thirty cases of
      Addision's disease were found from a total patient list of 323852, of which a
      third were tuberculous in origin and two-thirds non-tuberculous (12/30
      autoimmune, 8/30 unclassified). We conclude that Addison's disease is 2.4 times
      more common than previously reported. The tuberculous group was older, 65 vs 52
      years (p < 0.05), and had had the disease for longer than the non-tuberculous
      group, 20 vs 12 years (p < 0.05). There was no significant difference in the age
      at diagnosis.

PMID- 9196702
TI  - The acceptability of personal learning plans in vocational training.
AB  - Personal learning plans have been advocated as a means of introducing the
      principles of adult learning into general practice vocational training. The aim
      of this study was to investigate attitudes amongst general practice trainers and
      registrars to the introduction and use of personal learning plans. A
      questionnaire was sent to general practice trainers and registrars in one
      vocational training scheme prior to the introduction of personal learning plans.
      Overall, doctors in the training scheme were positive to the idea of personal
      learning plans. Trainers were significantly more positive towards introducing
      learning plans than their registrars. Registrars in their final general practice
      posts were significantly more positive towards the idea of learning plans than
      their hospital counterparts. Doctors who had completed membership of the Royal
      College of General Practitioners, usually trainers or final year registrars, were
      also more positive in their attitude. This pilot study suggests that most
      trainers and registrars were positive in their attitude towards personal learning
      plans prior to their introduction in the Lincoln vocational training scheme. The
      study cautiously suggests a wider use and evaluation of personal learning plans
      in vocational training.

PMID- 9196703
TI  - A six-year follow-up study of smoking habits and microvascular complications in
      young adults with type 1 diabetes.
AB  - One hundred insulin-dependent diabetic patients (age < 45 years, 53 smokers) were
      followed for six years. The age, duration of diabetes and mean glycated
      haemoglobin levels, were comparable between the smokers and non-smokers.
      Microvascular complications (retinopathy and increased urine albumin excretion)
      were commoner and more severe in the smoking group at six years, particularly in
      heavy smokers. Of the 45 original smokers reviewed at six years, 12 (27%) had
      stopped, six of whom had developed microvascular complications. Only two of the
      'heavy' initial smokers, likely to be at most risk, had stopped smoking, and
      three original non-smokers had started smoking.

PMID- 9196704
TI  - Solitary ileocolic arteriovenous malformation: spongostan and silk therapeutic
      embolisation.
AB  - A debilitated patient with liver cirrhosis and poor haemostasis had a severe
      lower gastrointestinal haemorrhage. A superior mesenteric arteriogram revealed an
      early persistent and promiment draining vein in the ileocolic artery. Two
      fragments of Spongostan and silk were used to embolise the bleeding artery and
      the haemorhage ceased immediately. No infarction of the embolised area was
      observed and the bleeding was controlled.

PMID- 9196705
TI  - Barium peritonitis: a rare complication of upper gastrointestinal contrast
      investigation.
AB  - Contrast examination of the gastrointestinal tract is rarely complicated by
      perforation. The colon and rectum are most commonly affected, with many
      perforations limited to the retroperitoneum. Generalised peritonitis is therefore
      rare, but is life-threatening and difficult to treat. We present two analogous
      cases in which extravasation of barium sulphate complicated contrast meal
      investigation. These cases illustrate important aspects in the management of this
      unusual occurrence.

PMID- 9196706
TI  - Delayed cyanide poisoning following acetonitrile ingestion.
AB  - Acetonitrile (methyl cyanide) is a common industrial organic solvent but is a
      rare cause of poisoning. We report the first recorded UK case. Acetonitrile is
      slowly converted to cyanide, resulting in delayed toxicity. We describe a case of
      deliberate self-poisoning by a 39-year-old woman resulting in cyanide poisoning
      11 hours later which was successfully treated by repeated boluses of sodium
      nitrite and thiosulphate. The half-life of conversion of acetonitrile was 40
      hours and harmful blood cyanide levels persisted for over 24 hours after
      ingestion. Departments treating or advising in cases of poisoning need to be
      aware of the delayed toxicity of acetonitrile. Monitoring in an intensive care
      unit of cases of acetonitrile poisoning should continue for 24-48 hours.

PMID- 9196707
TI  - Respiratory arrest during dipyridamole stress testing.
AB  - There is an increasing usage of radionuclide scanning to assess myocardial
      perfusion, with dipyridamole, the most commonly used stress agent. Although this
      is an effective, and usually very safe, means by which to assess myocardial blood
      supply, there have been several incidents of acute bronchospasm in asthmatic
      patients. There have, however, been no previous reports of respiratory arrest
      occurring in patients with emphysema. This case illustrates the dangers of
      administering intravenous dipyridamole, or even adenosine, to patients with
      chronic lung disease.

PMID- 9196708
TI  - Massive arterial bleeding from a single rectal vessel.
AB  - We report a case of massive rectal haemorrhage arising from a single ectatic
      arterial vessel above the haemorrhoidal cushion in normal rectal mucosa. Use of
      an anal retractor enable identification of the bleeding vessel and avoided a
      major laparatomy.

PMID- 9196709
TI  - Abdominal pain associated with cranial nerve palsy and peripheral neuropathy.

PMID- 9196710
TI  - Acute visual disturbance in a young adult.

PMID- 9196711
TI  - An unusual cause of large bowel obstruction.

PMID- 9196712
TI  - Familial chronic fatigue.

PMID- 9196713
TI  - An unusual rectal polyp.

PMID- 9196714
TI  - Severe refractory congestive cardiac failure in an elderly man.

PMID- 9196715
TI  - Spontaneous bacterial peritonitis due to Corynebacterium sp.

PMID- 9196716
TI  - No evidence of polarization sensitivity in freshwater sunfish from multi-unit
      optic nerve recordings.
AB  - The sensitivities of two species of sunfish (Lepomis gibbosus and Lepomis
      cyanellus) to the electric field (E-vector) of polarized light were assessed by
      compound action potential recordings from the optic nerve of live fish. Under
      white light and long wavelength adapting backgrounds, two cone mechanisms were
      found with maximum sensitivities in the long wavelength (lambda max approximately
      620 nm) and middle wavelength (lambda max approximately 530 nm) regions of the
      spectrum. In contrast to previous findings (Cameron & Pugh, 1991), no evidence of
      polarization sensitivity was observed for either species. We conclude from these
      results that post-larval sunfish do not exhibit polarization sensitivity.

PMID- 9196717
TI  - Is the use of underwater polarized light by fish restricted to crepuscular time
      periods?
AB  - We measured the spectral distributions of the underwater total and polarized
      light fields in the upper photic zone of meso-eutrophic waters (i.e., blue-green
      waters containing medium to high chlorophyll a concentrations). Per cent
      polarization levels during the day were always lower than 40%, but at crepuscular
      times these values could increase to 67%. A corresponding change occurred in the
      spectral distribution, with proportionately more shorter wavelength photons
      contributing to the total spectrum during crepuscular periods.
      Electrophysiological recordings from the optic nerve of rainbow trout subjected
      to light stimuli of varying polarization percentages show that the animal's
      threshold for detecting polarized light is between 63 and 72%. These
      physiological findings suggest that the use of water-induced polarized light cues
      by rainbow trout and similar percomorph fish should be restricted to crepuscular
      time periods.

PMID- 9196718
TI  - Motion integration over space: interaction of the center and surround motion.
AB  - Motion integration occurs over a restricted range of visual space. However, there
      have been studies suggesting interactions among motion detectors operating on
      widely separated spatial regions. To understand these lateral spatial
      interactions beyond motion pooling regions, we examined the effect of surrounding
      motion on the direction of the center stimulus under several stimulus conditions.
      We have found that there is a motion direction shift of the center stimulus
      caused by surrounding motion depending on its motion direction, spatial proximity
      to the center stimulus, contrast, speed, and the extent of motion area. This
      effect was observed both for monocular and dichoptic presentations of the
      pattern. However, the perceived direction shift decreased when the spatial
      frequency ratio of the center and surround stimuli varied, or a non-Fourier
      motion pattern was used for both center and surround stimuli. We present a model
      consisting of lateral inhibitory interactions between pattern motion unit
      networks to explain the direction shift observed in the experiments.

PMID- 9196719
TI  - Illusory contour-motion arising from translating terminators.
AB  - Periodic grating patterns were created by phase shifting or eliminating vertical
      columns of a fine line carrier grating oriented 45 deg. Motion was created by
      translating the patterns parallel to the carrier grating. This veridical motion
      was seen when terminators (i) were created in low-frequency carriers; (ii)
      terminated short lines; and (iii) moved slowly. In the complementary conditions
      an illusory contour-motion was seen perpendicular to the orientation of the
      terminator-defined contours. A model involving a competition between second-layer
      filters (encoding the orientation and motions of the terminator defined contours)
      and double endstopped mechanisms (signalling the presence of terminators) was
      developed and found to be in quantitative agreement with these data. Experiments
      with plaids composed of two such patterns were generally consistent with the
      results of the one-dimensional cases. Coherent "subjective contour plaid" motion
      was almost always seen when the two subjective contours had the same orientation
      and were perfectly phase aligned.

PMID- 9196720
TI  - Effect of image orientation contents on detection efficiency.
AB  - Contrast detection performance is known to be better for single component
      sinusoidal gratings than for sums of gratings at different orientations. A recent
      study Rovamo et al. (1994) (Investigative Ophthalmology and Visual Science, 35,
      2611-2619) showed that spatial integration is less effective for multiple
      orientation component than for single component gratings. This suggests an
      explanation that the size of a spatial integration window depends on the
      orientation contents of the stimulus. To test this hypothesis we designed a
      computational detection model and tested it against new experimental data. The
      model generates a cross-correlation template, the extent of which is limited both
      in the spatial and spatial frequency domain. The template is a copy of the band
      pass filtered signal weighted by a spatial window function. The spatial window
      function, which limits spatial integration, decreases with increasing orientation
      range of the stimulus. The experimental stimuli were composed of side-by-side
      located square shaped, one cycle, grating patches. The range of either grating
      orientations or phases within the patches as well as the number of patches in a
      stimulus were varied. We also measured detection efficiency for Bessel Jo images
      as a function of area. Human spatial integration became considerably weaker with
      increasing orientation range. The increasing phase range also reduced detection
      efficiency to some extent. Supporting the idea of the varying size of the spatial
      integration window, the computational model explained the orientation, phase, and
      Bessel Jo data well.

PMID- 9196721
TI  - The scintillating grid illusion.
AB  - Disk-shaped luminance increments were added to the intersections of a Hermann
      grid consisting of medium grey bars on a black background. Illusory spots, darker
      than the background, were perceived as flashing within the white disks with each
      flick of the eye. This striking phenomenon may be referred to as the
      scintillating grid illusion. We determined the conditions necessary for
      cancelling the Hermann grid illusion, as well as the luminance requirements and
      the size ratio between disks and bars that elicits the scintillation effect. The
      fact that scanning eye movements are necessary to produce the scintillation
      effect sets it apart from the Hermann grid illusion.

PMID- 9196722
TI  - In defence of "lateral inhibition" as the underlying cause of induced brightness
      phenomena: a reply to Spehar, Gilchrist and Arend.

PMID- 9196724
TI  - Trajectories of the human binocular fixation point during conjugate and non
      conjugate gaze-shifts.
AB  - This paper describes the spatial trajectories of the binocular fixation point
      (the intersection point of the two lines of sight) during gaze-shifts within a
      horizontal plane of regard. Gaze was voluntarily shifted between pairs of real,
      continuously visible LED targets that were either iso-vergent at 5-25 deg
      convergence (conjugate version saccades) or differed in vergence angle (by 5-20
      deg) as well as in direction (by 5-60 deg; combined version and vergence).
      Orientations of both eyes were recorded by phase detection in a homogeneous
      magnetic field with scleral sensor coils. "Conjugate" saccades showed an outward
      looping, curved trajectory as a result of transient divergence, typically
      associated with horizontal saccades. These outward loops were disproportionately
      larger for far than for near targets, due to the non-linear relation between
      vergence and distance. Transient divergence increased moderately in magnitude and
      duration when basic vergence increased from 5 to 25 deg. As a result, transient
      saccadic disparities increased in angular magnitude as targets got close.
      Increasing tonic vergence did not, however, slow down conjugate saccades, in
      contrast to the previously described dynamic slowing effects of vergence on
      version during gaze-shift involving simultaneous vergence and version changes.
      Convergent and divergent non-conjugate gaze-shifts each had characteristic
      trajectories; outward loops were much reduced in convergent and virtually absent
      in divergent movements. The saccadic component of non-conjugate gaze-shifts was
      preceded by a pre-saccadic vergence component in the direction of the imminent
      gaze-shift; its magnitude increased systematically with the increase in vergence
      demand and with the decrease in version demand. For both pre-saccadic convergence
      and divergence, this pre-saccadic part of the trajectory tended to follow an iso
      direction line through the target of origin; directional change did not start
      until the saccade began. This suggests that for targets that differ in direction
      as well as distance, control of the vergence and version components of the gaze
      shift can be dissociated to some degree. This seems to argue against models of
      binocular oculomotor control which assume that each eye responds primarily to its
      own target, and suggests rather that target vergence and target direction may be
      processed and responded to separately by ocular vergence and version, with a
      strong interaction between the two oculomotor activities whenever they occur at
      the same time.

PMID- 9196725
TI  - The effect of ocular torsional position on perception of the roll-tilt of visual
      stimuli.
AB  - Perceived postural orientation during whole-body roll-tilt is commonly inferred
      from settings of a visual line to the perceived gravitational horizontal or
      vertical. This inference assumes that the change in ocular torsional position
      (ocular counterrolling) which occurs during roll-tilt has no effect on the
      perceived orientation of the visual stimulus. We investigated this assumption by
      measuring, during whole body roll-tilt stimulation, settings of a visual line and
      a somatosensory bar to the perceived gravitational horizontal and comparing the
      difference in these settings to the objectively measured ocular torsional
      position for each subject. Two stimulus paradigms were used: one where the
      subject was given a roll-tilt stimulus and the eye torted, the other where there
      was eye torsion without a roll-tilt stimulus. In both paradigms there was a very
      close relationship in magnitude and direction between the difference in the
      settings of the two perceptual indicators to gravitational horizontal and the
      objectively measured ocular torsion. We conclude that change in ocular torsional
      position alone changes the perceived orientation of a visual line. The corollary
      is that settings of a visual line cannot be used to infer perceived postural
      orientation directly.

PMID- 9196726
TI  - Psychophysical evidence for a selective loss of M ganglion cells in glaucoma.
AB  - We measured resolution acuity at 12 different retinal locations using sinusoidal
      gratings in a group of normals, ocular hypertensives and glaucoma patients.
      Resolution was measured using both stationary gratings, which selectively
      stimulate parvocellular ganglion cells (P cells), and gratings which phase
      reversed at 30 Hz, which selectively stimulate a higher proportion of
      magnocellular ganglion cells (M cells). With stationary gratings, peripheral
      resolution was found to be significantly reduced in glaucoma patients and, to a
      lesser extent, in ocular hypertensives. When the stimuli phase reversed at 30 Hz
      these differences between groups were larger. The ratio of resolution with and
      without phase reversal also showed a significant difference between the three
      groups. These results provide strong psychophysical evidence for a selective loss
      of M ganglion cell density over P ganglion cell density in glaucoma.

PMID- 9196727
TI  - Using the POBF as an index of interocular blood flow effects during unilateral
      vascular stress.
AB  - Kergoat and Lovasik [(1994). Ophthalmic and Physiological Optics, 14, pp. 401
      407] reported that a transient decrease in ocular perfusion pressure (OPP)
      decreased the neural function in the test eye but increased the responsivity in
      the contralateral untouched (control) eye. Here the hypothesis tested was that a
      transient unilateral vascular stress would induce an increase in the Pulsatile
      Ocular Blood Flow (POBF) in the opposite eye. The POBF was measured in 20 healthy
      volunteers with normal intraocular pressure (IOP) and brachial blood pressure
      (BP). The OPP was decreased in the test (right) eye by scleral suction, and a
      Langham OBF system was used to make four readings of the POBF for each eye for
      baseline conditions, and when the OPP was decreased in the test eye alone by 20
      and 40% for a 2 min period. Each individual, as well as the group averaged data
      showed a progressive decrease in the POBF in the test eye during a stepwise
      reduction in the OPP. No change was found for the POBF for the control eyes.
      Within the limitations of the systems and testing procedures employed, it is
      concluded that unilateral alterations in the OPP do not cause a change in the
      POBF in the contralateral eye.

PMID- 9196728
TI  - Effects of nitric oxide on the horizontal cell network and dopamine release in
      the carp retina.
AB  - In the teleost retina the intercellular messenger nitric oxide can be synthesized
      by several cell types including cone photoreceptors and H1 horizontal cells,
      indicating a modulatory role within the outer plexiform layer, the first stage of
      the visual information processing. Therefore, the aim of this study was to
      elucidate the effects of nitric oxide on the physiology of cone horizontal cells
      in the intact retina. The nitric oxide donor sodium nitroprusside (0.5-2.5 mM)
      enhanced the light responsiveness of cone horizontal cells and reduced the degree
      of electrical coupling in the network. Furthermore, the spread of intracellularly
      injected Lucifer Yellow was restricted. The effects on light responsiveness and
      electrical coupling were qualitatively mimicked by 8-bromo-cGMP (0.5 mM) and
      could not be achieved by ferrocyanide (1 mM), the byproduct of nitric oxide
      liberation from nitroprusside. The effects of NO on the responsiveness of
      horizontal cells may be due to an action on green- and red-sensitive cones.
      Nitroprusside (0.1 mM) diminished the K(+)-stimulated release of endogenous
      dopamine by 50%, whereas the basal dopamine release was not affected, indicating
      that the effects on electrotonic horizontal cell coupling were not elicited by an
      NO-induced release of dopamine. With respect to the morphologic plasticity of the
      cone-horizontal cell synapse the inhibitor of endogenous nitric oxide synthesis L
      nitroarginine (0.1 mM) had no influence on the formation or retraction of
      spinules. These results show that NO affects the responsiveness and coupling of
      the horizontal cell network in a dopamine-independent way.

PMID- 9196729
TI  - Retinal dopamine depletion in young quail mimics some of the effects of ageing on
      visual function.
AB  - The hypothesis that retinal dopaminergic (DA) neurones are involved in the visual
      functions of interest was tested. The retinal DA in young quail was partially
      depleted by intravitreal injection of 6-hydroxydopamine (6-OHDA). It was found
      that the refractive state of 6-OHDA-treated birds became more myopic than normal
      (untreated) young, whereas the pupil diameter was not affected. The contrast
      sensitivity of 6-OHDA treated quail was significantly lowered (two to three
      times) at all spatial frequencies studied (0.25-5 c/d), and the peak latency of
      pattern electro-retinogram (PERG) response was prolonged by 3-4 msec (9%).
      Furthermore, the visual acuity and maximal amplitude of PERG response of the 6
      OHDA-treated young quail were lower than those of normals. From histochemical
      studies, it was revealed that the morphology of the DA cells of 6-OHDA-treated
      young appeared similar to those of the old quail; the DA cells of 6-OHDA-treated
      retinae were less fluorescent and 2.5-5 times less numerous than respective
      controls. Combining the PERG and the morphological results, it would seem that
      the retinal DA plays an important role in the visual functions studied, and that
      loss of retinal DA could underlie some of the visual changes which occur during
      ageing.

PMID- 9196730
TI  - The visual photopigments of simple deuteranomalous trichromats inferred from
      color matching.
AB  - Deuteranomalous trichromacy is the most common form of inherited color-vision
      deficiency. A modern description of its cause is a single abnormality: the normal
      middle-wave cone photopigment (M) is replaced by a shifted middle-wave pigment
      (M) that is shared by all deuteranomalous trichromats. This explanation, however,
      fails to account for the individual differences in color vision observed even
      within the sub-group of deuteranomals with good chromatic discrimination. An
      ensemble of color matches is used here to test whether these individual
      differences reflect differences in the wavelength of peak sensitivity (lambda
      max) of individual deuteranomals' cone photopigments. The results show variation
      in both the lambda max and the effective optical density of their cone pigments.
      The individual differences found in lambda max are in accord with recent
      molecular biological research that shows individual differences in the genes
      thought to encode deuteranomalous photopigments.

PMID- 9196731
TI  - Selective temporal interactions between processing streams with differential
      sensitivity for colour and luminance contrast.
AB  - Temporal interactions between spatially separated visual stimuli were
      investigated in human observers. Subjects had to judge whether briefly presented
      targets consisted of a single or a double flash. Simultaneous presentation of
      unattended single or double flash distractors impaired performance if target and
      distractor followed different time courses, confirming previous findings. This
      interference occurred only when targets had high luminance contrast or were
      isoluminant and when distractors had high or low luminance contrast, but not when
      targets had low luminance contrast or when distractors were isoluminant. Low
      luminance contrast distractors strongly influenced high luminance contrast
      targets but not vice versa. These results suggest that (i) information about the
      precise temporal structure of stimuli is conveyed preferentially by the luminance
      sensitive magnocellular system; and (ii) that this information influences
      judgements on the temporal patterning of signals transmitted by the colour
      sensitive parvocellular system.

PMID- 9196732
TI  - Comparison between spatial interactions in perceived contrast and perceived
      brightness.
AB  - We examined the spatial integration of simultaneously induced achromatic contrast
      and compared it to the spatial integration of simultaneously induced brightness.
      This study extends the work of Zaidi et al. [(1992). Vision Research, 32, pp.
      1695-1707], who showed that the total magnitude of induced brightness can be
      described as the weighted sum of the brightness induced by individual elements of
      the surround. The results show that contrast induction, though weaker than
      brightness induction, occurs over greater distances, and that a weighted spatial
      summation model for contrast induction requires an additional static non-linear
      compression, which is not required to model brightness induction. The analysis
      indicates that the contrast compression occurs prior to the lateral interactions
      that generate induced contrast.

PMID- 9196733
TI  - Absence of linear subthreshold summation between red-green and luminance
      mechanisms over a wide range of spatio-temporal conditions.
AB  - We have tested the independence of red-green chromatic and luminance mechanisms
      at detection threshold using a method of subthreshold summation. Stimuli were
      isoluminant red-green gratings and yellow-black luminance gratings that uniquely
      activate the red-green color and luminance mechanisms, respectively. Stimuli were
      Gaussian enveloped 0.25, 1 or 4 cpd sinewave gratings, counter-phase flickered at
      0, 5 or 9 Hz. The threshold detection of red-green color contrast was measured in
      the presence of a subthreshold amount of luminance contrast, and vice versa. The
      results allow a model of linear summation between the color and luminance
      mechanisms to be rejected, but are well fitted by a model, assuming that these
      mechanisms are independent but combine to determine detection by probability
      summation, with a high summation index (median value = 4). We conclude that there
      are independent red-green chromatic mechanism and luminance detection mechanisms
      over this range of spatio-temporal conditions.

PMID- 9196734
TI  - Non-Fourier information in bandpass noise patterns.
AB  - Random dot patterns and white-noise luminance textures are widely used in
      psychophysical experiments to study low-level visual processes. Because these
      noise patterns are broadband, bandpass filtered versions are employed to limit
      their frequency content. It is not recognized, however, that bandpass noise
      patterns have amplitude-modulation (AM) components. The AM signal is not present
      in the Fourier spectrum, nonetheless, it is a valid signal for second-order
      mechanisms. We characterize the properties of the AM signal in bandpass noise
      textures: the relevant periodicities of the AM signal are always much lower than
      the actual passband; the upper frequency limit of the AM signal increases with
      the linear bandwidth. We present psychophysical data to demonstrate the
      perceptual significance of the AM signal in bandpass noise. We provide a method
      for obtaining AM-free bandpass patterns, and compare psychophysical performance
      in experiments employing AM-present and AM-free bandpass noise patterns as
      stereoscopic stimuli. The results show that the AM component contributes to
      stereoscopic discrimination performance at large disparities. We suggest that the
      low-frequency AM signal is a possible confounding factor in experiments employing
      bandpass noise textures, and that linear filtering can isolate spatial scales
      effectively only for linear systems.

PMID- 9196735
TI  - Probed-sinewave paradigm: a test of models of light-adaptation dynamics.
AB  - Studies of light adaptation have, in general, employed either aperiodic or
      periodic stimuli. In earlier work, models originally developed to predict the
      results from one tradition failed to predict results from the other but the
      models from the two traditions could be merged to predict phenomena from both. To
      further test these merged models, a paradigm combining both types of stimuli was
      used. The threshold for a brief flash (the probe) was measured at various phases
      on a background that was varied sinusoidally in time. The probe threshold depends
      upon the phase at which it is presented for all background frequencies used, 0-16
      Hz. These threshold variations are not well described by a sinewave; the peak
      threshold is > 180 deg out of phase with the trough threshold. Further, the
      positions of the peaks and troughs shift fairly abruptly at background
      modulations of 4-8 Hz. The difference between the peak and trough thresholds
      varies as a function of temporal frequency in a manner approximating the temporal
      contrast sensitivity function. The dc level (mean threshold) does not. The peak
      trough difference dominates at low frequencies of background modulation, while
      the dc level dominates for higher frequencies. Existing models of light
      adaptation do not predict the key features of the data.

PMID- 9196736
TI  - Capture of visual direction: an unexpected phenomenon in binocular vision.
AB  - Binocular perception of visual direction is based on laws which were formulated
      more than 100 years ago. These laws govern the directions in which human beings
      perceive objects visible to both eyes (binocular objects) and objects visible to
      only one eye (monocular objects). We report here that the laws do not hold for
      monocular objects adjacent to binocular objects. The perceived directions of
      these monocular objects are captured by those of nearby binocular objects.
      Capture of binocular visual direction is an unexpected phenomenon because it
      refutes the generally accepted notion that a particular retinal location gives
      rise to a particular subjective visual direction. The practical consequence is
      that the subjective techniques for measuring eye position which are widely used
      in fundamental research and clinical practice are unreliable if they are used in
      densely structured stimuli. We suggest that capture results from a mechanism of
      lateral interaction between adjacent visual directions. This mechanism ensures
      that, despite eye movements, objects have the same spatial order in monocular and
      binocular vision. This conservation of spatial order also explains why retinal
      blind spots are not manifest in binocular vision.

PMID- 9196737
TI  - Convergence and divergence exhibit different response characteristics to
      symmetric stimuli.
AB  - The dynamic characteristics of horizontal convergence and divergence eye movement
      responses to symmetric stimuli were examined. Binocular eye movements were
      recorded in five, visually normal adult subjects using the infrared reflection
      technique for symmetric convergent and divergent blur-free, disparity-only, step
      stimuli of 2, 4, 8, 12, and 16 deg. The main sequence as well as other temporal
      parameters including latency, time-to-peak velocity, time constant, and total
      duration were analyzed. A number of fundamental differences in the response
      characteristics were found between convergence and divergence. First, the slope
      of the peak velocity vs amplitude curve was approximately twice as high for
      convergence than divergence. The results are consistent with neurophysiological
      findings in monkeys and most findings in humans. Second, the initial fast
      component for convergence exhibited a larger amplitude than for divergence. This
      may reflect differences in central neural gain for convergence and divergence.
      And, third, all temporally related components were shorter for convergence than
      divergence. These findings provide an overall framework for vergence control and
      suggest fundamental differences in neural processing delays and neural controller
      pathways for convergence and divergence.

PMID- 9196738
TI  - The horizontal optokinetic reflex of the opossum (Didelphis marsupialis aurita):
      physiological and anatomical studies in normal and early monoenucleated
      specimens.
AB  - In the opossum the symmetrical binocular horizontal optokinetic nystagmus gives
      way to an asymmetrical monocular reflex: the nasotemporal (NT) stimulation
      yielding lower gain than the temporonasal (TN). In adults, monocularly enucleated
      at postnatal days 21-25 (pnd21-25), the gain of NT responses is markedly
      increased, approaching that of TN. Severe cell loss was detected in the nucleus
      of the optic tract (NOT) on the deafferented side in early monoenucleated
      specimens. In normal animals retinal afferents to the NOT are all crossed, while
      in animals enucleated at pnd21-25 sparse uncrossed retinal elements were
      observed. Although this abnormal projection might influence the increased NT
      response in this subgroup, it is argued that the increased symmetry in
      monoenucleated opossums may be the result of changes mediated by the commissural
      connection between both NOTs.

PMID- 9196739
TI  - Curve detection in a noisy image.
AB  - In this paper we propose a new theory of the Gestalt law of good continuation. In
      this theory perceptual processes are modeled by an exponential pyramid algorithm.
      To test the new theory we performed three experiments. The subject's task was to
      detect a target (a set of dots arranged along a straight or curved line) among
      background dots. Detectability was high when: (a) the target was long; (b) the
      density of target dots relative to the density of background dots was large; (c)
      the local change of angle was small along the entire line; (d) local properties
      of the target were known to the subject. These results are consistent with our
      new model and they contradict prior models.

PMID- 9196740
TI  - Habituation-like effects cause a significant decrease in response in MRI
      neuroactivation during visual stimulation.
AB  - A wide range of rest/stimulus cycle durations (40-360 sec) is reported to have
      been used by various groups for MRI neuroactivation studies of the visual cortex.
      In this paper we demonstrate a clear habituation-like response for longer cycle
      durations which results in a halving of apparent activation between cycle
      durations of 138 and 276 sec. This has important implications, not only in terms
      of optimizing the technique, but also in providing an insight into the underlying
      physiological mechanisms.

PMID- 9196741
TI  - Remote sensing and disease control: past, present and future.

PMID- 9196742
TI  - Parasite genome analysis. Progress in the Leishmania genome project.
AB  - Genome projects have been established for 7 major groups of human parasitic
      infections: malaria, leishmaniasis, African trypanosomiasis, American
      trypanosomiasis, toxoplasmosis, schistosomiasis and filariasis. All except
      malaria and toxoplasmosis have come under the umbrella of the World Health
      Organization's Strategic Committee on Parasite Genome Analysis. The focus of this
      meeting of the Society was to review progress made in the Leishmania and African
      trypanosome genome projects. This paper introduces the genome projects and
      reviews briefly progress in pulsed-field gel karyotype mapping and gene
      identification via expressed sequence tag sequencing for the leishmaniasis genome
      project. The overall aim of the genome projects is to harness the latest
      developments in molecular genetic technology and sequence analysis for the rapid
      generation of new data which may, in turn, revolutionize our approaches to the
      study of the biology of these organisms.

PMID- 9196743
TI  - Parasite genome analysis. A global map of the Leishmania major genome: prelude to
      genomic sequencing.
AB  - In 1994, the World Health Organization (TDR) launched a new strategic initiative
      in parasite genome analysis, establishing international genome networks for
      filariae, Schistosoma, Leishmania, Trypanosoma brucei and T. cruzi. For
      Leishmania, a number of different but complementary approaches have been adopted
      by members of the Leishmania Genome Network. Our laboratory has been using cosmid
      clone fingerprinting to produce a physical map of the genome. Progress towards
      the completion of an integrated physical and biological map of L. major, and the
      preparations for genomic sequencing, are described.

PMID- 9196744
TI  - Parasite genome analysis. Genome research in Trypanosoma brucei: chromosome size
      polymorphism and its relevance to genome mapping and analysis.
AB  - Before the development of pulsed field gel electrophoresis (PFGE), little was
      known of the chromosomal organization of Trypanosoma brucei. This technique first
      revealed that the nuclear genome was subdivided into distinct size classes of
      chromosomes, subsequently shown to have disparate genetic roles in the life cycle
      of the parasite. PFGE also facilitated the determination of chromosome ploidy and
      the observation that apparent homologues often differed significantly in size
      within and between isolates. While the biological reasons underlying this
      plasticity may prove very interesting, nevertheless it could pose real problems
      for the global analysis of the T. brucei genome. Therefore, before undertaking
      large scale physical mapping, it is necessary to determine the number and size of
      chromosomes in the reference stock; to compare these to the chromosomes of other
      stocks to determine the relative sizes of homologues; and to investigate the
      deoxyribonucleic acid content of the size of polymorphic regions in order to
      assess how these may affect the execution of a physical mapping programme.

PMID- 9196745
TI  - Tropical aspects of viral hepatitis. Hepatitis C.
AB  - This paper reviews our current understanding of hepatitis C infection in tropical
      countries. Since its discovery in 1989, hepatitis C has been recognized as an
      important disease in many tropical countries. In Egypt the prevalence in some
      sections of the population may-exceed 20%. In most tropical areas, however, the
      epidemiology of hepatitis C infection is poorly defined. There are clear
      variations in the distribution of genotypes in different areas and this may be
      one of the factors which influence the natural history of infection in different
      regions of the world. Routes of infection in tropical countries are poorly
      defined, most carriers having no clear risk factors for infection. There is some
      speculation that inadequate sterilization of medical equipment may be a route of
      infection in some areas. A combination of factors may result in an increased risk
      of hepatocellular carcinoma developing in patients from the tropics infected with
      hepatitis C and the prognosis may be worse due to co-infection with hepatitis B
      and human immunodeficiency virus, both of which may lead to accelerated liver
      disease. Prospects for disease control are poor due to the difficulty of
      developing a vaccine to the virus.

PMID- 9196746
TI  - Tropical aspects of viral hepatitis. Hepatitis E.
AB  - Hepatitis E (HEV) is a faeco-orally transmitted hepatitis virus. It has many
      features similar to hepatitis A but some differences, notably the high mortality
      caused by HEV in pregnant women. A vaccine is being developed but at the moment
      only a clean water supply will reduce the number of cases in areas where the
      virus is endemic.

PMID- 9196747
TI  - Household responses to malaria and their costs: a study from rural Sri Lanka.
AB  - A study of the cost of malaria at the household level, community perceptions,
      preventive measures and illness behaviour linked to the disease was undertaken in
      5 villages in the dry zone of Sri Lanka. The surveyed community had a high
      knowledge of malaria, although side effects of antimalarial drugs were often
      confused with symptoms of the disease. The community sought prompt diagnosis and
      treatment at 'western-type' facilities, with 84% making use of government
      facilities as their first choice and 16% preferring private facilities. The
      preventive measures used were burning coils (54% of families) and special leaves
      (69% of families), and 93% of the families had their houses sprayed with
      insecticides. Average direct expenditure on a single malaria episode was $3 US,
      with some families spending more than 10% of the annual household net income per
      episode. The highest expenditure was on special diets for the sick person, to
      neutralize the perceived heating effect of the disease and its treatment.

PMID- 9196748
TI  - Effect of intestinal helminthiasis on school attendance by early primary
      schoolchildren.
AB  - Stool examination of 249 early primary schoolchildren at 2 schools in north
      eastern peninsular Malaysia revealed that 73 were infected with Ascaris
      lumbricoides, 103 with Trichuris trichiura, and 18 with hookworms. Infected
      children were treated with a single dose of 400 mg of albendazole. The school
      attendance records during a 60 d period before treatment and 2 consecutive 60 d
      periods after treatment were examined. The absenteeism rate did not improve more
      among infected children after treatment than it did among the uninfected control
      children. The correlation between worm intensity and the number of lost school
      days was poor. There was no evidence that intestinal helminthiasis caused school
      absenteeism among this group of children.

PMID- 9196749
TI  - Epidemic typhus in a prison in Burundi.
AB  - The International Committee of the Red Cross investigated an outbreak of fever of
      unknown origin in Ngozi prison, Burundi, which resulted in a crude mortality rate
      of 2.61% in January 1996. A definite diagnosis of epidemic typhus caused by
      Rickettsia prowazekii was established by enzyme-linked immunosorbent assay using
      specific antigens. Control measures included complete cleansing of the prison
      with cyfluthrine, shaving and dusting all prisoners with permethrin 0.5% dusting
      powder, and replacement of all mattresses and clothes. All prisoners and guards
      received a single dose of doxycyline (100 mg) simultaneously. The crude mortality
      rate dropped abruptly to 1.27% in February 1996 and remained at or below 0.5%
      from March onwards. Health authorities and medical agencies working in Burundi
      need to consider epidemic typhus in the differential diagnosis of fever of
      unknown origin in order to be able to take appropriate control measures in time.

PMID- 9196750
TI  - Reporting notifiable diseases: methods for improvement, attitudes and community
      outcome.
AB  - Notification is an important source of health information. However, it suffers
      from the serious limitation of under-reporting, especially in 'third world'
      countries. The aims of this study were to assess the impact of a special
      notification nurse and ward notification register on the rate of notification
      from a general medical unit, the knowledge and attitudes of intern medical
      officers regarding notification, and the community outcome of notification in a
      Sri Lankan setting. Overall, appointment of a special nurse improved notification
      rates from 9.7% to 62.1%, and the addition of a special ward notification
      register further improved the rate to 95.1% The results also indicated that,
      although a majority of intern medical officers were aware of notifiable diseases
      and the importance of notification, only a few of them always notified notifiable
      diseases. One of the main reasons given for this was that the majority of them
      felt that no useful action was taken on notifications by the preventive health
      authorities, a view that was held because there was no feedback information
      regarding the notifications. However, during the period of this study nearly 80%
      of all notifications were successfully investigated by the relevant medical
      officer of health office. The appointment of a nurse dedicated to notification
      and introduction of a ward notification register could greatly improve
      notification rates. Better communication between curative and preventive health
      sectors would improve attitudes of doctors regarding notification.

PMID- 9196751
TI  - Invasion and growth of Plasmodium falciparum is inhibited in fractionated
      thalassaemic erythrocytes.
AB  - Epidemiological and clinical studies have indicated that the thalassaemias may
      confer protection against malaria. The study reported here investigated this
      protective effect in vitro, using a new approach which controls for the potential
      effect of red cell size and age on the virulence of the parasite. A Percoll
      density gradient method was used to separate alpha- and beta-thalassaemic trait,
      haemoglobin H and normal red blood cells (RBC) into fractions of different
      density. Correlations between RBC density, age and size in fractions of all
      genotypes were established using red cell creatine as an index of cell age. The
      development of Plasmodium falciparum over 3 erythrocytic cycles (144 h) in whole
      blood as well as fractionated samples was monitored by slide microscopy and flow
      cytometry. A significantly reduced rate of parasite invasion and growth was
      demonstrated in RBC from all thalassaemic genotypes tested. Poor reinvasion rates
      were noted in the second and third cycles. Increased duration of culture and red
      cell age also had a greater negative impact on parasite growth in thalassaemic
      RBC. This poor growth rate was also associated with the arrest of parasite growth
      at the schizont stage (schizont maturation arrest) and the accumulation of
      abnormal, trophozoite/schizont stage parasites in the older thalassaemic RBC
      fractions. These findings suggest a defect in the number and viability of
      merozoites generated by parasites growing in thalassaemic RBC. Age related
      factors such as oxidant stress may play a key role in mediating this kind of
      protective mechanism and deserve further investigation.

PMID- 9196752
TI  - Occurrence of a community with high morbidity associated with Schistosoma mansoni
      infection regardless of low infection intensity in north-east Brazil.
AB  - To establish the relationship between schistosome-associated morbidity and
      infection intensity in northeast Brazil, a parasitological and ultrasonographical
      study was carried out on 484 inhabitants of 4 villages (I, II, III and IV) in Sao
      Lourenco da Mata, Pernambuco, Brazil, where schistosomiasis is endemic.
      Quantitative stool examination using Knight's method demonstrated a high
      prevalence and moderate intensity of Schistosoma mansoni infection, and also that
      the subjects in village IV had a significantly lower prevalence and intensity of
      infection than those of the other villages. By ultrasonography, periportal
      fibrosis (PPF) and splenomegaly were found in 52% of the 299 infected subjects
      and 66% of the 146 infected subjects aged over 16 years old, respectively; 32%
      and 31% of the 299 infected subjects had abnormally high values of total bile
      acid (TBA) and alkaline phosphatase (ALP) activity, respectively. Liver and
      spleen size, PPF, and serum level of TBA and ALP were not correlated with
      infection intensity. There was no significant difference in the morbidity
      assessed by liver and spleen size, PPF, and serum analysis between the subjects
      in village IV and the other villages. These findings suggest the occurrence of a
      community with high morbidity associated with schistosomiasis regardless of low
      infection intensity.

PMID- 9196753
TI  - Onchocerciasis hyperendemic in the Unturan mountains: an extension of the endemic
      region in southern Venezuela.
AB  - A new region with human onchocerciasis is reported in the Unturan mountains,
      South Venezuela, affecting Yanomamo populations not surveyed in previous studies
      conducted in the Venezuelan-Brazilian border area. Its distribution probably
      extends towards the Upper Toototobi endemic area in Brazil. The age-standardized
      prevalence of Onchocerca volvulus microfilariae (mf) (67%), the prevalence of
      infection in those aged > or = 20 years (86%), and the community microfilarial
      load (CMFL) (24 mf/mg), are consistent with hyperendemic transmission. Both
      prevalence and mean intensity increased monotonically with age without reaching a
      plateau, the highest values being recorded in the > or = 45 years age class
      (respectively, 95% and 42 [geometric mean of Williams] or 172 [arithmetic mean]
      mf/mg). The degree of parasite overdispersion (measured by the variance/mean
      ratio) also increased with host age. The CMFL value, the presence of sclerosing
      keratitis, hanging groin, and severe skin lesions, indicated that the infection
      poses an important public health problem in the region.

PMID- 9196754
TI  - The vector status of Simulium damnosum on the island of Bioko in Equatorial
      Guinea.

PMID- 9196755
TI  - A reagent strip antigen capture assay for the assessment of cure of
      schistosomiasis patients.

PMID- 9196756
TI  - A polymerase chain reaction-based assay for detection of Wuchereria bancrofti in
      human blood and Culex pipiens.
AB  - Human blood samples and indoor-resting Culex pipiens were collected in 33
      randomly selected houses from different sectors of a village in the Nile Delta of
      Egypt which was endemic for Wuchereria bancrofti. Blood was also collected from
      subjects with no history of living in filarial endemic areas. Human blood samples
      were divided and assessed by both membrane filtration and polymerase chain
      reaction (PCR). Similarly, mosquito samples were assessed by both dissection and
      PCR. Blood pools representing each household were tested by PCR. If a pool gave a
      positive result, then individual blood specimens were also tested by PCR. Of the
      33 houses tested, both membrane filtration and blood pools assayed by PCR
      identified 14 (42.4%) 'infected houses'. PCR detected parasite deoxyribonucleic
      acid (DNA) in blood pools from an additional 3 households that gave negative
      results by membrane filtration. Of 178 endemic blood samples tested by membrane
      filtration, 22 (12.3%) had microfilariae and all were individually positive by
      PCR. Although microfilaria counts were lower in blood collected during the day
      than in night-collected blood, the PCR results were consistent, regardless of
      time of collection. All non-endemic blood samples were negative by PCR. Among the
      33 houses rested, mosquito pools assayed by PCR identified 17 (51.5%) as
      'infected households'. Of these, 8 houses (47%) contained at least one
      microfilaraemic resident. One 'infected household' was identified by mosquito
      dissection. We concluded that PCR is a powerful epidemiological tool for
      screening villages for the prevalence of W. bancrofti. PCR detection of W.
      bancrofti DNA in blood-fed mosquitoes could be used initially to locate endemic
      areas with transmission of bancroftian filariasis. PCR detection of W. bancrofti
      DNA in blood collected during the day could then be used to assess W. bancrofti
      infection rates.

PMID- 9196757
TI  - Coma scales for children with severe falciparum malaria.
AB  - The Blantyre coma scale (BCS) is used to assess children with severe falciparum
      malaria, particularly as a criterion for cerebral malaria, but it has not been
      formally validated. We compared the BCS to the Adelaide coma scale (ACS), for
      Kenyan children with severe malaria. We examined the inter-observer agreement
      between 3 observers in the assessment of coma scales on 17 children by measuring
      the proportion of agreement (PA), disagreement rate (DR) and fixed sample size
      kappa (kappa n). We assessed the sensitivity and specificity of the scales in
      detecting events (seizures and hypoglycaemia) in 240 children during admission
      and the usefulness of the scales in predicting outcome. There was considerable
      disagreement between observers in the assessment of both scales (BCS: PA = 0.55,
      DR = 0.09 and kappa n = 0.27; ACS: PA = 0.36, DR = 0.31, and kappa n = 0.31),
      particularly with the verbal component of the BCS (kappa n = 0.02). Compared to
      the ACS, the BCS was more specific (0.85 for BCS and 0.80 for ACS), but less
      sensitive (0.25-0.69 vs. 0.38-0.88 respectively) in detecting events and was a
      worse predictor of neurological sequelae. The BCS provided a better overall
      assessment of a child's incapacity from falciparum malaria, but the ACS was more
      useful in assessing neurological disturbances.

PMID- 9196758
TI  - Incidence of clinical malaria in pregnant women exposed to intense perennial
      transmission.
AB  - The interaction between pregnancy and malaria attacks was investigated from 1990
      to 1994 among women in the village of Dielmo, a holoendemic area in Senegal where
      malaria transmission is intense and perennial. Clinical and parasitological data
      collected during the daily follow-up of 48 pregnancies among 31 women were
      compared with those collected from the same women using the same methods during
      the year which preceded or followed their pregnancy. The parasite prevalence,
      mean and maximum parasite density in Plasmodium falciparum infections were
      significantly higher during pregnancy. The incidence rate of malaria attacks was,
      on average, 4.2 times higher during pregnancy than during the control period.
      Although most pregnancies were not associated with a malaria attack and the
      incidence of malaria attacks decreased as the number of previous pregnancies
      increased, a significant increase in risk of malaria attacks among multigravidae
      was noted until the fifth pregnancy.

PMID- 9196760
TI  - Cyclospora cayetanensis in an asymptomatic patient infected with HIV and HTLV-1.

PMID- 9196759
TI  - Circulating villous lymphocytes--a link between hyperreactive malarial
      splenomegaly and splenic lymphoma.
AB  - Significant numbers of villous lymphocytes were noted in the blood of patients
      with a clinical diagnosis of hyperreactive malarial splenomegaly (HMS) in Ghana.
      Demographic and haematological data were recorded from 22 patients with massive
      splenomegaly. Additional investigations included lymphocyte immunophenotyping,
      protein electrophoresis and immunoglobulin gene rearrangements. Although all
      patients had over 30% villous lymphocytes and no leucocytosis, 7 had no evidence
      of a monoclonal disorder. Immunophenotyping and the presence of monoclonal
      lymphocytes identified 3 further patients with B-cell splenic lymphoma with
      villous lymphocytes (B-SLVL). HMS and SLVL co-existed in the same, predominantly
      female, patient population and were indistinguishable except by molecular
      analysis of lymphocytes. The discovery of the uncommon villous lymphocytes in
      both non-malignant and malignant disorders in the same geographical area
      suggested that HMS and SLVL are pathophysiologically related. In Caucasians with
      SLVL the malignant cells arise from B-cells that have undergone antigen
      selection. We postulate that the excessive proliferation of polyclonal B
      lymphocytes, driven by frequent exposure to malaria, predisposes to the emergence
      of a malignant lymphoma, B-SLVL, in tropical West Africa.

PMID- 9196761
TI  - Clinical significance of neurocysticercosis in endemic villages. The
      Cysticercosis Working Group in Peru.
AB  - Cerebral cysticercosis is the main cause of late-onset epilepsy in most
      developing countries. Data on the neuroepidemiology of cysticercosis in endemic
      populations is scarce. In an endemic village on the northern coast of Peru, 49
      individuals with neurological symptomatology (41 epileptic and 8 non-epileptic)
      were screened for antibodies to Taenia solium, using a serum
      electroimmunotransfer blot assay. Fifteen subjects were seropositive, 14 (34%) of
      those with epilepsy but only one (13%) of those who were non-epileptic. A history
      of passing proglottides was associated with positive serology. Thirteen of the 15
      seropositive individuals underwent cerebral computed tomography; only 7 (54%)
      were abnormal. A randomly selected sample of 20 pigs from the village was also
      tested, and 6 (30%) were seropositive. This study demonstrated the importance of
      cysticercosis in the aetiology of epilepsy in endemic villages and the close
      relationship between porcine and human infection.

PMID- 9196762
TI  - Isolation of a flavivirus related to the tick-borne encephalitis complex from
      human cases in Saudi Arabia.
AB  - A flavivirus related to the tick-borne encephalitis complex was isolated from the
      blood of 6 male butchers, aged 24-39 years, in Jeddah, Saudi Arabia in November
      and December 1995. Two of the patients died and the other 4 recovered completely.
      Four more patients, 3 males and 1 female, were diagnosed serologically by
      immunoglobulin M capture enzyme-linked immunosorbent assay and seroconversion in
      acute and convalescent blood samples examined by indirect immunofluorescent test
      using Vero cells infected with the isolated virus. The virus identity was
      confirmed at the Centers for Disease Control and Prevention, Fort Collins,
      Colorado, USA, by the polymerase chain reaction; it was closely related to
      Kayasanur Forest disease virus. All infected patients had similar clinical and
      laboratory symptoms and signs, including fever, headache, generalized body aches,
      arthralgia, anorexia, vomiting, leucopenia, thrombocytopenia, elevated liver
      enzymes (serum glutamic oxalacetic and serum glutamic pyruvic transaminases),
      elevated creatinine phosphokinase, and elevated blood urea. One patient developed
      symptoms of encephalitis, but survived without any sequel. Skin rash developed in
      2 patients, morbilliform on the hands, feet, and lower abdomen of one patient and
      purpuric associated with melaena in the second patient. Eight of the 10 confirmed
      patients were working with sheep, and the disease may be a zoonotic viral
      infection.

PMID- 9196763
TI  - Recurrence of epidemic conjunctivitis caused by enterovirus-70 in Pune, India.

PMID- 9196764
TI  - Giant millipede 'burns' and the eye.
AB  - A retrospective review of 8 cases of millipede 'burns' (caused by Polyconoceras
      sp. [= Salpidobolus sp.]) of the eye and periorbital tissues seen in a specialist
      ophthalmology unit over 6 years at Madang General Hospital, Papua New Guinea, was
      conducted. Such cases comprised 0.06% of the 14,000 patients seen in the same
      period. All cases were seen in the rainy season. Apart from one adult, all cases
      were children (age range 9 months-7 years). Clinical manifestations included a
      'burn' of periorbital skin (all 8 cases), marked periorbital oedema (3 cases),
      conjunctivitis (2 cases), and keratitis (one case). All patients recovered fully
      with standard topical ophthalmic therapy. Despite anecdotal reports that
      blindness is a likely sequela of millipede 'burns' of the eye, it did not occur
      in this, the only published series of the condition.

PMID- 9196766
TI  - Megaloblastic anaemia among Somalis in north-eastern Kenya.

PMID- 9196765
TI  - Clinical indicators of envenoming and serum levels of venom antigens in patients
      bitten by Bothrops lanceolatus in Martinique. Research Group on Snake Bites in
      Martinique.
AB  - An enzyme-linked immunosorbent assay was developed to measure venom antigen
      levels in the serum of 40 patients bitten by Bothrops lanceolatus. The grading
      system used for the severity of envenomation (grades 1 to 4, minor to major) was
      predominantly based on the presence of local signs. Serum venom levels increased
      with the grade of severity (P < 0.001, by Spearman's rank correlation test); they
      were 6 +/- 6 ng/mL (mean +/- SD) in clinically non-envenomed patients (grade 1, n
      = 3), 7.6 +/- 11.7 (n = 17), 44.3 +/- 41.8 (n = 17), and 80.3 +/- 34.1 ng/mL (n =
      3) in patients diagnosed as grade 2, 3 and 4 respectively. However, venom
      antigens could not be detected in the serum of 54% of patients who showed
      clinical signs of envenomation. Most patients diagnosed as grade 2, 3 or 4 were
      given 20, 40 and 60 mL of a monospecific F(ab')2 antivenom, respectively. Venom
      concentrations > or = 15 ng/mL were observed in all patients with progressive
      aggravation of swelling despite the use of early antivenom therapy. No venom was
      detectable in blood samples taken after completion of serotherapy. All patients
      recovered. These results confirm the efficacy of both the clinical severity
      scoring system used and the therapeutic regimen.

PMID- 9196767
TI  - Single dose artemisinin-mefloquine versus mefloquine alone for uncomplicated
      falciparum malaria.
AB  - The efficacy of the combination of a single oral dose of 500 mg artemisinin with
      a single 500 mg oral dose of mefloquine (AM) in the treatment of uncomplicated
      falciparum malaria was compared to mefloquine therapy alone (M) in a double
      'blind' randomized study in an endemic area in the south of Viet Nam where single
      low dose treatment was employed and where mefloquine had been recently
      introduced. 231 patients, 117 AM and 114 M, were studied. Failure of therapy
      occurred in 1 AM patient and in 3 M patients. The radical cure rate was 84% for
      the AM regimen and 65% for the M regimen (P = 0.002). Recrudescence (including an
      unknown percentage of reinfections) occurred in 15% of AM patients and in 30% of
      M patients (P = 0.01). The mean parasite clearance time was 40 h (SD = 16) for AM
      and 60 h (SD = 27) for the M regimen (P = 0.0001). No effect of artemisinin was
      noted on gametocytes present on admission, but new gametocytes developed less
      frequently in the AM group. The addition of a single dose of 500 mg artemisinin
      to 500 mg mefloquine increased the efficacy and reduced the rate of
      recrudescence, but this regimen was not adequate and, for short course regimens,
      more doses of artemisinin as well as higher, doses of mefloquine should be
      studied.

PMID- 9196768
TI  - Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium
      falciparum malaria.
AB  - The pharmacokinetic properties of oral artesunate (3 mg/kg) were determined in 10
      Vietnamese children, aged from 6 to 15 years, with acute falciparum malaria of
      moderate severity. Plasma concentrations were measured using a bioassay and
      expressed in terms of antimalarial activity equivalent to dihydroartemisinin, the
      principal biologically active metabolite. Oral artesunate was absorbed rapidly
      with a mean time to peak plasma bioactivity of 1.7 h (95% confidence interval
      [95% CI] 0.8-2.6). There was wide variation in peak plasma concentrations with a
      mean value equivalent to 664 ng of dihydroartemisinin/mL (95% CI 387-9410, range
      179-1395) and a four-fold variation in the area under the plasma concentration
      time curves. Elimination from plasma was rapid with a mean (95% CI) half-life of
      1.0 h (95% CI 0.8-1.4). Plasma antimalarial levels were below the limit of
      detection in all cases by 12 h, despite the relatively high dose of artesunate
      used. Oral artesunate is rapidly absorbed and rapidly eliminated in children with
      moderately severe malaria but there is considerable variation between
      individuals.

PMID- 9196769
TI  - Side effects of mefloquine prophylaxis for malaria: an independent randomized
      controlled trial.
AB  - A prospective randomized double-'blind' trial was undertaken during a military
      exercise in East Africa to determine whether there was a significant difference
      in the incidence of side effects experienced by soldiers taking mefloquine 250 mg
      weekly compared with those taking chloroquine 300 mg weekly and proguanil 200 mg
      daily as chemoprophylaxis for malaria. Subject to their informed voluntary
      consent, male soldiers who were not aviators were included in the study.
      Identical questionnaires were completed voluntarily at the end of 2 and 8 weeks.
      Symptoms were classified by nature into-'all', 'neuropsychological', 'enteric'
      and 'other', and by severity into 'severe' and 'very severe'. The proportions of
      respondents experiencing side effects were compared to seek statistically
      significant differences between the chemoprophylactic groups. Questionnaire 1 was
      completed after 2 weeks by 183 of 317 subjects (58%) randomly assigned mefloquine
      and by 176 of 307 subjects (57%) randomly assigned chloroquine-proguanil. The
      incidence of putative side effects was not significantly different between the
      groups (71/183 vs. 70/176), odds ratio 0.96 (95% confidence interval [CI] 0.63 to
      1.47). Questionnaire 2 was completed after 8 weeks by 145 of 317 subjects (46%)
      randomly assigned mefloquine and by 142 of 307 subjects (46%) randomly assigned
      chloroquine-proguanil. The incidence of putative side effects was still not
      significantly different between the groups (95/145 vs. 103/142), odds ratio 0.72
      (95% CI 0.43 to 1.19). None of the subjects developed a serious
      neuropsychological reaction. Among respondents, 12.8% and 38% admitted lack of
      full compliance at 2 and 8 weeks, respectively. Exclusion of these subjects
      during a secondary analysis did not affect the results. None of the subjects
      developed malaria in the 12 months following return to the UK. Subject to the
      limitations of a response rate that was smaller than desired and the fact that
      the study was conducted in fit male military personnel, these results support
      evidence which indicates that mefloquine is no more toxic than chloroquine
      proguanil.

PMID- 9196771
TI  - Plasmodium falciparum: adaptation in vitro of isolates from symptomatic
      individuals in Gabon: polymerase chain reaction typing and evaluation of
      chloroquine susceptibility.

PMID- 9196770
TI  - Hyperpigmented dermal macules in children following the administration of
      Maloprim for malaria chemoprophylaxis.
AB  - The occurrence of an unexpected side effect following the use of Maloprim
      (pyrimethamine/dapsone) for malaria chemosuppression in 3-59 months old children
      in Sierra Leone is reported. As part of a trial of chemoprophylaxis and
      insecticide-impregnated bed nets, 2000 children received either Maloprim or
      placebo; 4% of children who received Maloprim fortnightly for more than 3 months
      developed hyperpigmented macules, whereas none of the children who received
      placebo did so. Histopathological examination of full thickness skin biopsies
      showed macrophages containing melanin in the dermal layer. Clustering of cases
      was noted among siblings, suggesting the possible involvement of genetic factors
      in the pathogenesis of these skin reactions. One child was accidentally re
      exposed to Maloprim after the drug had been withdrawn and he developed a severe
      reaction. No other serious side effect was noted. Hyperpigmented lesions similar
      to those reported in this study have been described previously in patients with
      leprosy treated with dapsone, and the dapsone component of Maloprim is the likely
      cause of the skin reactions seen in children given this drug for malaria
      chemoprophylaxis.

PMID- 9196772
TI  - pfmdr1 gene mutation and clinical response to chloroquine in Yaounde, Cameroon.

PMID- 9196773
TI  - A seven days course of eflornithine for relapsing Trypanosoma brucei gambiense
      sleeping sickness.
AB  - Forty-seven patients with a relapse following a first treatment of Trypanosoma
      brucei gambiense trypanosomiasis were treated with a 7 d course of intravenous
      eflornithine (100 mg/kg every 6 h) and followed for 2 years. Four patients died
      after treatment, 2 of them possibly due to trypanosomiasis. One patient was
      completely lost to follow-up, 36 were followed for at least one year, and 25 have
      completed the 2 years' follow-up. Only one patient, a 5 years old child,
      subsequently relapsed. Considering this child and 2 of the fatalities as
      treatment failures, the rate of failure was 6.5%. A 7 d course of intravenous
      eflornithine is an adequate treatment for cases of Gambian trypanosomiasis
      relapsing after treatment with another drug.

PMID- 9196774
TI  - Response of babesiosis to a combined regimen of quinine and azithromycin.

PMID- 9196775
TI  - Modelling the dynamic effects of community chemotherapy on patterns of morbidity
      due to Schistosoma mansoni.
AB  - This paper uses a mathematical framework to predict the long-term consequences of
      chemotherapy for the age distribution of schistosomiasis morbidity. The framework
      incorporates a previously validated transmission model, which is here extended to
      capture effects on 2 forms of Schistosoma mansoni morbidity: early disease
      exemplified by hepatomegaly and late disease exemplified by Symmer's fibrosis.
      The main aim of this analysis is to show how such an approach could be used to
      explore the probable public health consequences of decades of control. It is
      suggested that this procedure could usefully inform current approaches to the
      design of long-term control programmes.

PMID- 9196776
TI  - Albendazole for the treatment of Mansonella perstans filariasis.

PMID- 9196777
TI  - Daily fluctuation of levels of circulating cathodic antigen in urine of children
      infected with Schistosoma mansoni in Brazil.
AB  - The fluctuation of circulating cathodic antigen (CCA) levels in urine was studied
      in 69 Brazilian school-children infected with Schistosoma mansoni and compared to
      egg counts. Faeces and urine samples were simultaneously collected at 7 times
      during a period of 2 weeks. CCA was determined by enzyme-linked immunosorbent
      assay and could be detected in 96% of the urine samples; the individual mean CCA
      level ranged from 609 to 350,700 pg/mL. 90% of the faecal samples contained S.
      mansoni eggs and the individual mean egg output ranged from 9 to 5510 eggs/g. The
      Spearman rank correlation coefficient between these individual means was 0.69.
      Kendall's coefficient of concordance (W) was 0.88 for CCA levels and 0.80 for egg
      counts.

PMID- 9196778
TI  - Demonstration of immunoglobulin G antibodies against Onchocerca volvulus
      excretory-secretory antigens in different forms and stages of onchocerciasis.
AB  - The excretory-secretory (E-S) products of helminths are considered to comprise
      immunogenic molecules of high diagnostic value. In the present study, the
      serodiagnostic potential of the E-S products released in vitro by cultured female
      Onchocerca volvulus was investigated by enzyme-linked immunosorbent assay (ELISA)
      and Western blotting using 190 serum samples from persons infected with O.
      volvulus and unexposed persons. The sensitivity of detection of anti-O. volvulus
      E-S antibodies was 94% for sera from patients with the generalized form of
      onchocerciasis and 100% for sera from patients with the chronic hyperreactive
      form (sowda). 95% of the sera from amicrofilaridermic persons, who subsequently
      became microfilaridermic within 2 years, reacted with O. volvulus E-S antigens
      and the donors were therefore regarded as having had a prepatent infection when
      first examined. These sera gave higher (P < 0.05) ELISA optical densities than
      sera from the same persons obtained when they had become patent, indicating a
      loss of antibody reactivity after emergence of microfilariae. The specificity of
      the E-S ELISA was 100% when sera of subjects infected with Wuchereria bancrofti
      were used, and at least 88% for Mansonella perstans sera. In Western blot
      analysis, the sera of persons with generalized onchocerciasis recognized 7
      protein bands. Many E-S proteins were stained less intensely by the sera of
      subjects with generalized onchocerciasis than by the sera of sowda patients.
      Similar antigen bands were demonstrated using sera from the persons with
      prepatent infections.

PMID- 9196780
TI  - Heritability of the trait for human infectivity in genetic crosses of Trypanosoma
      brucei ssp.

PMID- 9196779
TI  - Genetic structure of Plasmodium vivax isolates in India.
AB  - Variations in the allelic composition of glucose phosphate isomerase (GPI), NADP
      dependent glutamate dehydrogenase (GDH) and adenosine deaminase (ADA) enzyme
      systems of Plasmodium vivax were observed in isolates of Indian origin in 1985
      1993. No significant difference was observed in allelic frequencies in different
      years. The data indicated random distribution of GPI, GDH and ADA alleles among
      the isolates, suggesting that loci for these enzymes were not linked. A high
      proportion of the isolates comprised at least 2 genetically distinct clones, the
      mean number of clones per isolate being 1.4. There was no significant difference
      in the number of oocysts in Anopheles stephensi fed on uniclonal and multiclonal
      isolates. No difference was observed in the proportions of uniclonal and
      multiclonal isolates during low and high transmission periods.

PMID- 9196781
TI  - Nitrate levels in malaria.

PMID- 9196782
TI  - Graham Greene, the fathers and leprosy transmission.

PMID- 9196783
TI  - Blood films in the diagnosis of anaemia.

PMID- 9196784
TI  - Object relations couple therapy.
AB  - The authors describe Fairbairn's view of the personality as a system of parts of
      self and object in dynamic relation, formed in the context of dependent early
      relationships and replayed in the intensely intimate and physical relationship of
      marriage. Through Klein's concept of projective identification, a spouse finds
      lost parts of the self in the partner, where they may flourish and be
      reintegrated into the self or they may be held hostage. Marriage is an
      opportunity for reworking the dynamic relation of parts of the self as they are
      modified through mutual unconscious interaction with the spouse, but it may
      become a closed system that inhibits growth of the individual partners. Object
      relations couple therapy aims to breach the closed system of the unhappy
      marriage, and offers an enlarged space for understanding that encourages the
      spouses to provide a better holding environment for each other. Not directive,
      didactic or symptom-focused, object relations therapy values affect, silence,
      body language, fantasy, dreams, and transference phenomena as necessary for
      reaching the unconscious in order to achieve insight. The object relations
      therapist interprets defenses against anxieties that underlie repetitive patterns
      of unhelpful behavior, and works toward understanding. As the clinical vignettes
      show, therapists use countertransference to understand the couple's shared
      transference from inside their experience. The engine of therapeutic change in
      this model is the therapist's self. The process of therapy improves the couple's
      capacity for containing each other's projections instead of refusing to resonate
      with them or being overtaken by them to the detriment of the self. A cycle of
      regression and progression in the couple's ability for containment is found as
      therapy proceeds. The goal of therapy is to enable the projective and
      introjective identificatory system of the marriage to function with greater
      concern for the other and respect for the self.

PMID- 9196785
TI  - The clinical risk management of stalking: "someone is watching over me....".
AB  - I have offered ten guidelines for the clinical risk management of stalking: a
      team approach, personal responsibility for safety, documentation and recording,
      no initiated contact, protection orders, law enforcement and prosecution,
      treatment if indicated, segregation and incarceration, periodic violence risk
      assessment, and the importance of dramatic moments. Although criminal stalking is
      not expected in mental health practice, the interpersonal anguish that often
      erupts in psychotherapy, and the reporting of relational intrusions that disrupt
      the safety of treatment, may foreshadow such distressing and potentially
      dangerous behavior. It is my hope that the clinician will be prepared for such
      untoward events, and these guidelines will shape an appropriate professional
      response. For as Racine wrote in 1667, "The heart that can no longer love
      passionately, must with fury hate." (Andromache, 1, trans. Robert Henderson).

PMID- 9196786
TI  - Relational psychoanalysis: a historical background.
AB  - The author hopes Relational Psychoanalysis, as a broad emphasis on Self and
      Other, will not develop into another constraining and dogmatic school. In
      studying its sources I wish to maintain a dialectical view, and avoid ancestor
      worship. For me, its roots can be found both in the inner contradictions of
      theorists, such as Freud and Klein, and in the intense and generative dyads they
      created, particularly Freud-Ferenczi and Klein-Winnicott, where the defiance of
      the older colleague's authority led the younger one toward better understanding
      of relational dynamics. While both Fairbairn and Sullivan failed to draw full
      clinical conclusions from their innovative theoretical models, their work-as well
      as the contributions of Balint, Guntrip, Racker, Kohut and others, and the
      growing dissatisfaction with the traditional drive-defense model-helped Greenberg
      and Mitchell formulate in the 1980s their new relational integration. These ideas
      are most fully expressed in the Relational Track of NYU's postdoctoral
      psychoanalytic program, and in the journal Psychoanalytic Dialogues. Among major
      issues debated by relational theorists are motivation (wish/need/drive),
      knowledge and truth in relationships (social constructivism), relational
      developmental models, the nature of intersubjectivity, the significance of
      feminism and postmodernism for psychoanalysis, and the implications of a
      relational approach for technique and for training.

PMID- 9196787
TI  - The synergy of group and individual psychotherapy training.
AB  - Although this paper has focussed on ways in which group-therapy experience
      differs from the experience of individual therapy for the beginning therapist,
      all of the differences discussed are only matters of degree and thus are
      important in both individual and group therapy. Group-therapy experience tends to
      enhance the visibility of important aspects of all forms of psychotherapy and
      therefore should be looked at as a useful tool in learning all forms of
      psychotherapy. Experience in group psychotherapy should ideally precede or occur
      simultaneously with initial exposure to individual therapy rather than following
      afterwards as an option, as is usually the case in current psychotherapy training
      programs. The most important skill to acquire in learning psychotherapy is the
      sophisticated ability to listen. To do so involves attending to content, affect,
      the patient's and one's own verbal language, body language, and meta
      communications, conscious as well as unconscious. Group psychotherapy experience
      early in one's development as a psychotherapist can be a powerful tool in
      developing this ability to listen. Being part of the group process allows a
      unique level of intimacy that is probably more equal and vulnerable than in other
      forms of therapy. The use of the self, and the ability to trust in the process
      without using theory as a barrier between ourselves and our patients, but rather
      as a bridge to greater understanding, can all flow from the unique experience of
      leading a psychodynamic group.

PMID- 9196788
TI  - Adolescent sexual offenders: a self-psychological perspective.
AB  - Following a request for assistance in formulating a treatment philosophy for
      adolescent sexual offenders, a qualitative study of seven adolescent offenders
      was designed with a view to elaborating pre-offense, and post-offense dynamics.
      The point of departure was the hypothesis that sexual offending had relation to
      object relations. It was further hypothesized that offenders' object relations
      and self-development had been disfigured in childhood and adolescent development.
      The developmental theories of Mahler, Stern, Winnicott, and Kohut were reviewed
      in order to shed light on the connection between disfigured self-development and
      sexual offending. Mahler's work suggested that anomalies during the separation
      individuation process were heavily implicated. Winnicott's thinking on
      transitional functioning in potential space and his employment of the concepts of
      the true self and false self were especially useful. These bodies of work were
      assimilated to Kohut's theory of self development in which three nuclear sectors
      of the self, namely, the grandiose-exhibitionistic sector, the idealizing
      voyeuristic sector, and the twinship-alterego sector, gradually coalesce and
      cohere through the moderating influence of parental empathy with the child's
      developmental tasks. Where such empathy is unforthcoming, or when the normal
      parental functions are obliterated by traumatic experiences of abuse, unmoderated
      needs for exhibitionism and voyeurism continue through childhood, adolescence,
      and adulthood. Victims of sexual offending were hypothesized to perform functions
      of restoration and preservation of a chronically weak and threatened self. The
      sample's interview transcripts were qualitatively analyzed and aggregated.
      Analysis suggested that, indeed, offenses appeared to have been motivated to
      preserve a weakened sense of self and that the thoughts and perceptions
      surrounding the offenses resonated with expressions of problematic separation
      from parental objects. In addition, it was noted that in the post-offense period,
      offenders had become subject to close supervision, or proctoring, from both
      formal and informal systems. In close supervision, offenders tended to rapidly
      crystallize a foreclosed, negative, deviant sexual identity in defense of
      unmoderated narcissism. Other observations were that intrafamilial offending was
      consistent with enmeshment in the family, adjudication and apparent treatment
      readiness, while extrafamilial offending was consistent with exclusion from the
      family, no adjudication and resistance to treatment.

PMID- 9196789
TI  - Techniques to accelerate dynamic psychotherapy.
AB  - The techniques described above outline specific ways to deepen the patient's
      affective experience within an emotionally close therapeutic relationship. When
      effective, they all enhance the patient/therapist bond, raise self-esteem, reduce
      defensiveness and anxiety, and facilitate emotional healing. Psychodynamic
      treatment, long or short, is a complex process uniquely constructed by each
      therapist/patient pair. AEDP strategies are not intended as recipes for
      treatment. Good dynamic work depends on the therapist's ability to grasp the
      patient's capacities and limitations, understand relational dynamics, and
      interact with the patient in an empathically attuned, emotionally receptive, and
      flexible way. In that context, these strategies can be helpful tools to
      facilitate and accelerate the process. The choices made by AEDP--privileging
      adaptive strivings over defensive reactions, the stance of emotional engagement
      rather than neutrality and abstinence, the focus on health and change over
      pathology and stasis--are informed by traditional STDP aims to maximize depth,
      effectiveness, and efficiency. AEDP's contribution is a set of techniques relying
      on a response repertoire that is available to a wide range of therapists.
      Therapists can use these techniques to be more effective while simultaneously
      retaining the experience of speaking with patients in an authentic voice.

PMID- 9196790
TI  - Impasses in the supervisory process: a resident's perspective.
AB  - The purpose of this paper was to identify examples of supervisory and treatment
      impasses that occur in psychotherapy training and to examine aspects of their
      resolution. A self-administered questionnaire was completed by resident
      volunteers in two Ontario university departments of psychiatry. Despite responses
      indicating an apparent overall contentment with psychotherapy supervision,
      resident case vignettes detailed the most frequent impasse situations between
      themselves and supervisors. The majority were unresolved leading to distressing
      experiences for residents and failed psychotherapies for patients. Supervision
      promoting learning, combined treatments, and discussion of similar impasses,
      while focusing on the resident's immediate concerns and
      transference/countertransference issues appeared responsible for resolution. This
      pilot study underscores the need for an enhanced focus on the recognition and
      repair of impasses and highlights recommendations concerning the need for
      continuing education devoted to the supervisory alliance. We believe this will
      increase the residents' ability to effectively treat their patients. This paper
      emphasizes the experience of residents in psychotherapy supervision. A future
      study will focus on the supervisor's experience of impasses in supervision.

PMID- 9196791
TI  - The use of metaphor by an artless first-time psychotherapist.
AB  - The experience in a psychiatric residency of being a psychotherapist for the
      first time can be overwhelming and anxiety-provoking. This paper examines a first
      psychotherapy case which utilizes a theory-distant approach based on the use of
      metaphor. Metaphorical theory is reviewed, and potential benefits and pitfalls of
      using metaphor are examined. An in-depth case study is done, focusing on the
      following six metaphors: Art as Psychotherapy; Psychotherapy as Art; The World Is
      a Trap; Mothers Are Martyrs; StepMothers Are Evil; and Artists Are Crazy. Each
      metaphor was utilized in multiple layers through the course of the therapy. Some
      of the current research in the use of metaphor in psychotherapy is reviewed.
      Through this approach, I was able to develop necessary psychotherapeutic skills
      without being overwhelmed by traditional theories such as Freudian, Object
      Relations or Self Psychology. I conclude that the use of metaphor with my first
      psychotherapy patient strengthened the therapeutic alliance, allowed an
      idiosyncratic language to develop in the therapy, structured recurrent themes,
      and permitted me to respect the patient's defenses.

PMID- 9196792
TI  - Cognitive behavior therapy.

PMID- 9196793
TI  - A study of early pregnancy factor activity in preimplantation.
AB  - PROBLEM AND METHOD: Early pregnancy factor (EPF), an Immunosuppressive substance,
      which appears in pregnant women's sera 48 h after fertilization, is a kind of
      pregnancy-specific protein. To determine whether the EPF activity could be a
      super early indicator of pregnancy, we used rosette inhibition assay to detect
      EPF activity in the sera, collected from 70 women 2-7 days after ovulation
      intending to conceive monitored by ultrasonography. Simultaneously we selected 40
      non-pregnant sera and 12 early-pregnant sera as negative control and positive
      control, respectively. RESULTS: The results of this study demonstrated that EPF
      activity is detected in 35 women's sera out of 70 women within 2-7 days after
      ovulation, and 28 women out of the 35 were pregnant, which was known by follow
      up, and 7 were not pregnant, possibly due to either false positive results or
      embryo loss because of preimplantation failure, thus causing no pregnancy. The
      other 35 out of 70 had no EPF activity and 34 of them were not pregnant, which
      was known by follow-up, but one case became pregnant, which was false negative
      result. Our study showed that diagnosis of the super early pregnancy could be
      made by detecting EPF activity in maternal serum within the time of
      preimplantation. The accuracy of pregnancy diagnosis by this method is 88.6%,
      with a false negative rate of 3.4% and a false positive rate of 17.1%. The beta
      HCG level was measured from the above 70 women's sera in order to contrast EPF
      activity. All of the sera collected 2-6 days following ovulation indicated that
      there were lower beta-HCG values in very early pregnancy (> or = a5 mIU/ml). On
      the seventh day after ovulation, EPF activity was detected in 11 out of 15 sera
      with only 2 of them with a b-HCG level that reached or slightly surpassed that of
      the early pregnancy diagnosis (5 mIU/ml and 5.4 mIU/ml, respectively). This
      demonstrated that beta-HCG is not the earliest signal of pregnancy; otherwise the
      EPF activity is one that appears 2-6 days earlier than beta-HCG appears. We
      measured the progesterone level of the 48 sera from the 70 collected above within
      2-7 days postovulation and found most of them reached the level of progesterone
      in the luteal phase (7.5-98.3 nmol/L). This indicated that ovulation had taken
      place in these women, which was in accordance with observations by
      ultrasonography. CONCLUSIONS: Our study showed that diagnosis (of 88.6%) of super
      early pregnancy could be made with an accuracy of 88.6% by detecting EPF activity
      in maternal serum within 2-days after ovulation. This offers a basis for
      pregnancy diagnosis for the women who attempt to terminate their pregnancy safely
      or who conceive unexpectedly, and it contributes to family-planning.

PMID- 9196794
TI  - Effects of serum from pregnant versus non-pregnant women on natural killer cell
      activity.
AB  - PROBLEM: To test the effect of serum obtained from in vitro fertilization-embryo
      transfer (IVF-ET) patients on the healthy volunteers natural killer (NK) cell
      activity. METHOD OF STUDY: Retrospective non-randomized clinical study.
      Suppressive effect on NK cell activity was measured with serum obtained from 25
      pregnant and 24 non-pregnant women during IVF-ET procedure. RESULTS: Suppressive
      serum effect of volunteers' NK cell activity was significantly higher in pregnant
      than in non-pregnant women (P < 0.01). CONCLUSIONS: The suppressive activity of
      serum from pregnant women on NK cell suppression activity was useful in
      predicting the establishment of a successful pregnancy.

PMID- 9196795
TI  - Changes in T, B, and NK lymphocyte subsets during and after normal pregnancy.
AB  - PROBLEM: Pregnancy affects the maternal immune system and the clinical course of
      maternal diseases. Here we report the changes in the detailed lymphocyte subsets
      of helper T cells, suppressor T cells, CD5+ B cells, T cell receptor (TCR) alpha
      beta-positive T cells (T alpha beta cells), TCR alpha beta-negative T cell (T
      gamma delta cells), and other during and after pregnancy through to one year
      postpartum, and discuss the significance of the changes. METHOD: The absolute
      numbers of helper T cells, suppressor T cells, cytotoxic T cells, TCR alpha beta
      negative T cells (T gamma delta cells), CD5- B cells, CD5+ B cells, and NK cell
      subsets were examined by two-color flow cytometry in peripheral blood from 51
      healthy non-pregnant women, 106 healthy pregnant women, and 148 healthy
      postpartum women. RESULTS: In early pregnancy, the numbers of suppressor T cells
      and NK cells with strong cytotoxicity (NK+3 cells) increased, and the number of
      cytotoxic T cells decreased. In late pregnancy, the helper T cell and NK+3 cell
      numbers decreased. T alpha beta, CD5- B and CD5+ B cells decreased during
      pregnancy. After delivery, helper T cells and cytotoxic T cells increased from 1
      to 4 months postpartum, and suppressor T cells increased at 7 months postpartum.
      TCR alpha beta-negative T cells increased at 4 to 10 months postpartum. Both CD5-
      and CD5+ B cells decreased further at 1 month postpartum, but CD5+ B cells
      increased markedly at 7 to 10 months postpartum. CONCLUSIONS: These data indicate
      that 1) early increases of suppressor T cells and NK+3 cells during pregnancy may
      be related to the mechanism to accept or reject the fetus in early pregnancy,
      respectively; 2) late decreases of helper T cells and NK+3 cells may be related
      to the maintenance of pregnancy: 3) postpartum increases of helper T cells,
      cytotoxic T cells, TCR alpha beta-negative T cells (T gamma delta cells), and
      CD5+ B cells may be related to the postpartum aggravation of autoimmune diseases;
      and 4) the immunological effects of pregnancy remains until about 1 year after
      delivery.

PMID- 9196796
TI  - Lactation stage-dependent changes of lymphocyte subpopulations in mammary
      secretions: inversion of CD4+/CD8+ T cell ratios at parturition.
AB  - PROBLEM: Determination of lactation stage-dependent changes in levels of
      lymphocyte subpopulations in milk. METHOD: Flow cytometric assay was used to
      identify and assay lymphocyte subpopulations in bovine milk at different stages
      of lactation. RESULTS: Lymphocyte subpopulations in mammary secretions of dairy
      cows change during the lactation cycle. In involuting glands (dry gland),
      approximately 80-90% of lymphocytes were CD2+ T cells. The proportion of CD2+ T
      cells, however, decreased to approximately 50% at the colostral stage an
      fluctuated between 50 to 60% in normal (mature) milk. Throughout the lactation
      stages, less than 5% were B cells as identified by the monoclonal antibodies
      against CD21 and MHC class II antigens. Subset analysis showed, however, that the
      proportion of CD5+ T cells decreased from 90% in involuting gland secretions to
      75% in colostrum (peripartum stage), and to approximately 40-50% in the normal
      (mature) milk, CD4+ T cells constituted between 45 to 55% of lymphocytes in the
      dry gland secretion but decreased drastically at parturition and maintained at
      the level below 20% throughout normal lactation. In contrast, the proportion of
      CD8+ T cells in the dry gland secretion was low, between 30 to 40%, but increased
      steadily, in an inversely-related manner with that of CD4+ T cells, to
      approximately 40-50% at parturition and maintained at approximately 30-40% during
      the normal lactation stage thereafter. Two-color immunofluorescence study
      revealed further that practically all of the CD8+ cells in dry gland secretions
      were CD2+, and approximately 40% of them were CD5-. Throughout the lactation
      cycle, WC1+ gamma delta T cells comprised only 2 to 5% of lymphocytes in mammary
      secretions. CONCLUSIONS: T lymphocyte subpopulations change dynamically during
      stages of the lactation cycle. The selective migration of T lymphocyte
      subpopulations to and from the mammary gland, and their functional roles in the
      immune competence and regulation of the dam and sucklings remain to be
      elucidated.

PMID- 9196797
TI  - Estrogen inhibits fetal thymocyte development in vitro.
AB  - PROBLEM: Transient involution of the maternal thymus in mice is known to occur
      during pregnancy. We have previously reported that the hormone responsible for
      this involution is estrogen. Interestingly, although estrogen crosses the
      placenta, fetal thymus gland enlarges with advancing gestational age. It is not
      known if fetal thymocytes are resistant to estrogen or if there are other factors
      that prevent estrogen from exerting an effect on the development of fetal
      thymocytes. Therefore we studied the effect of estrogen on isolated fetal thymic
      glands in vitro. METHOD OR STUDY: Pregnant Balb/c mice were sacrificed at 15 days
      gestation and fetal thymic lobes were obtained from all fetuses. The glands were
      cultured in vitro using either control medium or medium to which estrogen was
      added in two concentrations of 0.5 mg/ 100 ml and 1.0 mg/100 ml. After 12 days of
      organ culture, total thymocyte counts and phenotypic analysis by three color flow
      cytometry were performed by using monoclonal antibodies to surface markers of T
      cells subsets. RESULTS: Estrogen treatment caused a marked suppression of the
      total number of fetal thymocytes. All CD4 and CD8 defined T cell subsets were
      reduced with a disproportionate loss of CD4+ single positive (SP), CD8+ SP:
      CD4+CD8+ double positive (DP) cells. The early thymocyte developmental stages,
      based on CD44 and CD25 expression, revealed the CD4-CD8-CD3- triple negative
      compartment (TN) to be composed of almost entirely the earliest population
      (CD44+CD25-) with the remaining maturational stages depleted. CONCLUSIONS: This
      study demonstrates that fetal thymus removed from the intact fetus is susceptible
      to the inhibitory effects of estrogen. Since the fetal thymus enlarges with
      advanced gestational age, it is clear that the intact fetus invokes a regulatory
      mechanism which neutralizes the anti-lymphopoietic action of estrogen observed in
      the adult female.

PMID- 9196798
TI  - Expression of Fas ligand in murine ovary.
AB  - Corresponding to the expression of Fas in the ovarian oocytes as previously
      reported (Guo et al., Biochem Biophys Res Commun 1994; 203:1438-1446; Mori et
      al., JSIR 1995; 9:49-50), the expression of Fas ligand (FasL) in the ovarian
      follicle was found to be restricted in the area of granulosa cells by the
      indirect immunofluorescence (IIF) test. Reverse transcriptase/polymerase chain
      reaction (RT/PCR) technique coupled with Southern blot hybridization analysis
      showed that the highest level of FasL mRNA was demonstrated in murine ovaries and
      granulosa cells 1 day after the administration of pregnant mare's serum
      gonadotropin (PMSG), while the level of FasL mRNA became very weak on the day 5,
      respectively. The observed gradual decrease in FasL mRNA could not be attributed
      to a generalized degradation of cellular RNA during atresia, as evidenced by the
      presence of constitutive expression of elongation factor 1 alpha (EF-1 alpha)
      mRNA in murine ovaries and granulosa cells treated with PMSG. Furthermore, in
      situ hybridization analysis with a FasL-specific probe confirmed that FasL was
      specifically localized in the granulosa cells of most follicles and its
      expression was regulated by PMSG administration. FasL localized in granulosa
      cells might possibly play an important role in the formation of the ovarian
      atretic follicles, most likely depending on PMSG administration.

PMID- 9196799
TI  - Major goat sperm 105 kDa maturation antigen: purification, characterization, and
      effect of its antiserum on acrosin activity.
AB  - A ConA binding membrane glycoantigen of 105 kDa molecular mass was purified from
      mature goat sperm by ion exchange and gel filtration chromatography. Of the
      detergents examined, the anionic deoxycholate was found to be highly effective in
      maximum solubilization of this sperm membrane antigen (SMA2). The analysis of the
      saccharide components by gas liquid chromatography revealed that the 105 kDa
      antigen (SMA2) contained the highest amount of mannose, followed by galactose and
      glucose in a ratio of 4:3:1. One amino sugar, N-acetylglucosamine, was also found
      to be present in the polysaccharide branching of the SMA2 antigen. The internal
      sulfydryl linkage is essential for the maintenance of the protein backbone of 105
      kDa antigen. The antigen selectively resides on the anterior head of goat sperm.
      The binding of anti-SMA2 antibody to the integrated mature goat spermatozoa
      inhibited the release of acrosin after the induction of spermatozoa with Ca
      ionophore.

PMID- 9196800
TI  - Intratumor heterogeneity of morphometric and stereologic variables in primary
      ovarian tumors and their omental metastatic deposits.
AB  - OBJECTIVE: To compare quantitative pathologic variables assessed in primary
      ovarian tumors and metastatic tumor deposits in the omentum and compare their
      prognostic value. STUDY DESIGN: In 29 cases of advanced ovarian cancer the mean
      nuclear area (MNA), volume-weighted mean nuclear volume (vv), volume percentage
      epithelium (VPE) and mitotic activity index (MAI) were assessed in both the
      primary ovarian tumor and its metastatic deposits in the omentum. Differences
      were evaluated using the Wilcoxon rank sum test for paired observations, and
      coefficients of variation were calculated in each case over the values obtained
      from the tumor in the ovary and omentum. RESULTS: Intraobserver and interobserver
      reproducibility of MNA, VPE and MAI were all good to very good except for the
      interobserver reproducibility for vv, which was moderate. MNA and vv, correlated
      well, both in the primary ovarian tumor (r = .88) and omental metastasis (r =
      .87). No significant differences were found between the assessments of MNA, vv,
      and MAI in the primary ovarian tumor and its omental metastasis, whereas
      significant differences were found for VPE. However, in some patients the nuclei
      tended to be larger and the VPE lower in the omental metastasis than in the
      primary ovarian tumor. No important impact of the origin of tumor tissue was
      reflected in the prognostic value of the nuclear features. Patients were grouped
      prognostically differently for the assessment of MAI and VPE in the primary
      ovarian tumor and its omental metastasis. CONCLUSION: Quantitative pathologic
      variables for prognostic purposes are best assessed in the primary ovarian tumor.
      Measurements in the metastatic deposits may be helpful in understanding processes
      of metastasis in advanced ovarian cancer.

PMID- 9196801
TI  - Minimum spanning tree analysis in advanced ovarian carcinoma. An investigation of
      sampling methods, reproducibility and correlation with histologic grade.
AB  - OBJECTIVE: To investigate sampling methods and reproducibility of minimum
      spanning tree (MST) variables in advanced ovarian cancer and their discriminative
      power for histologic grade. STUDY DESIGN: For the methodologic investigation, 30
      cases of advanced ovarian cancer of the common epithelial types were used. These
      cases were equally distributed over the three histologic grades according to
      independent, "blind" assessments by three observers: well (n = 10), moderately (n
      = 10) and poorly (n = 10) differentiated. Additionally, the discriminative power
      of the MST variables for histologic grade was assessed in 64 cases (double-blind
      agreement upon grade by two observers). Measurements were performed on
      hematoxylin-eosin-stained tumor sections. In each field of vision the centers of
      gravity of tumor cell nuclei were interactively marked using a digitizing video
      overlay system, and an MST was computed. From each MST the number of points,
      total line length, average line length, minimum line length, maximum line length
      and percentage of points with one, two three and four neighbors were obtained.
      Optimal performance (coefficient of error < 5%) of the method was established
      when the MST was constructed in 12 systematically randomly selected fields of
      vision at a final magnification of 1,900x. RESULTS: Intraobserver and
      interobserver reproducibility showed good correlation coefficients for most MST
      variables. Univariate analysis revealed that total, average and minimum line
      length were significantly different between the three histologic grades. With a
      jacknifed stepwise discriminant analysis an overall correct classification of 75%
      for the three histologic grades was achieved in 64 cases, using the average line
      length, standard deviation of the line length and total line length. CONCLUSION:
      MST syntactic structure analysis offers an easy, fast and very reproducible
      technique that may be of help in objective grading of advanced ovarian cancers.
      Further studies are under way to investigate the prognostic value of MST analysis
      in advanced ovarian cancer.

PMID- 9196802
TI  - Comparison of conventional microscopy and digitized imaging for diagnosis in
      serous effusions.
AB  - OBJECTIVE: To compare diagnoses made from conventional microscopy and digitized
      imaging in preparation for teleconsultation cytopathology services that are
      affordable and efficient. STUDY DESIGN: One hundred six consecutive serous
      effusions received in the cytopathology laboratory of a general hospital in Porto
      Alegre, RS, Brazil, were studied. The diagnoses by the senior cytopathologist at
      the conventional microscope were considered the standard and identified 61 cases
      negative and 45 positive for malignant cells (40 epithelial and 5 nonepithelial).
      The same pathologist digitized 461 selected fields for analysis by a second
      experienced cytopathologist (observer A) and a senior cytotechnologist (observer
      B) without knowledge of the standard diagnoses. Ten cases were studied in daily
      sessions of one hour each. The diagnoses were negative for malignant cells,
      positive for malignant cells (epithelial) and positive for malignant cells
      (nonepithelial). RESULTS: The following kappa values were found: 0.91 (observer A
      and observer B versus standard) and 0.86 (observer A versus observer B).
      CONCLUSION: Remote digitized imaging diagnosis in serous effusions is possible
      and has a high degree of concordance with diagnosis by conventional microscopy.
      Similar studies involving a larger group of cytopathologists and
      cytotechnologists should be done to identify interobserver variability.

PMID- 9196803
TI  - Image analysis of murine chromatin fiber structure after in situ digestion with
      restriction endonucleases.
AB  - OBJECTIVE: To determine and quantify the differences produced in chromatin
      structure after selective in situ DNA digestion with restriction endonuclease
      (RE). STUDY DESIGN: Chromatin fiber structure from a murine cell line was
      analyzed under light and electron microscopy before and after in situ digestion
      with AluI, HinfI and HaeIII using digital image analysis (DIA). The proposed DIA
      based method entails the generation of a binary image and a skeleton
      characteristic of the chromatin fiber. Morphologic features (surface, perimeter,
      shape, number of triple points and Euler number) of the chromatin structure can
      then be quantified from the digitized images. The results of these experiments
      were compared with those obtained from direct digestion of naked DNA using the
      same endonucleases in an attempt to correlate the distribution of restriction
      sites, according to the DNA fragment size obtained, with the extent of chromatin
      disorganization after RE in situ digestion. RESULTS: Homologous chromatin fiber
      regions are differentially affected by the action of each RE, although they are
      indistinguishable under light microscopy. CONCLUSION: The proposed analytical
      routine constitutes a valuable tool for uncovering subtle alterations in the
      structure of chromatin fiber that has been modified under different experimental
      conditions.

PMID- 9196804
TI  - Contribution of quantitative lectin histochemistry to characterizing well
      differentiated, dedifferentiated and poorly differentiated liposarcomas.
AB  - OBJECTIVE: To find new diagnostic markers in the group of lipomatous tumors.
      STUDY DESIGN: The histochemical lectin staining pattern was characterized in a
      series of 45 lipomatous lesions, including 10 typical lipomas, 6 atypical
      lipomas, 8 well-differentiated, 6 myxoid, 5 dedifferentiated and 10 pleomorphic
      liposarcomas. Three lectins were used-peanut (Arachis hypogaea) agglutinin, which
      binds to terminal Gal(beta 1,3)GalNAc residues; wheat germ (Triticum vulgare)
      agglutinin (s-WGA, the succinylated form of WGA), which binds to ((1-4)-D
      GlcNAc)n and Neu5NAc residues; and jack bean (Concanavalia ensiformis) agglutinin
      which binds to alpha-D-Man and alpha-D-Glc residues. Histochemical staining was
      quantitatively measured by means of a cell image processor. RESULTS: In the case
      of certain carbohydrate residues, typical lipomas closely resemble atypical
      lipomas, which in turn closely resemble well-differentiated liposarcomas; typical
      lipomas differ significantly from well-differentiated liposarcomas. This
      indicates that atypical lipomas, or at least some of them, could represent a
      biologic link between typical lipomas and well-differentiated liposarcomas. While
      well-differentiated and pleomorphic liposarcomas differed significantly from each
      other, the poorly differentiated component of dedifferentiated liposarcomas
      included histochemical lectin properties, which were common to both well
      differentiated and pleomorphic liposarcomas. CONCLUSION: Some atypical lipomas
      exhibit glycohistochemical characteristics that are common to those of well
      differentiated liposarcoma. The poorly differentiated component of
      dedifferentiated liposarcomas remains more differentiated in terms of
      glycohistochemical markers than do poorly differentiated pleomorphic
      liposarcomas.

PMID- 9196805
TI  - Detection of apoptosis in colorectal carcinoma by light microscopy and in situ
      end labelling.
AB  - OBJECTIVE: An in situ end labelling reaction (ISEL) was recently described for
      the detection of apoptotic cells in histologic sections. We compared the
      efficiency and reproducibility of this assay with those of routine light
      microscopy using hematoxylin and eosin (H&E) in the quantitation of apoptotic
      cells in colorectal cancer. STUDY DESIGN: Paraffin-embedded archival tissues from
      15 colorectal carcinomas were used in the study. ISEL was performed using
      terminal deoxynucleotidyl transferase, biotinylated deoxyuridine triphosphate and
      streptavidin-alkaline phosphatase. RESULTS: Apoptotic indices determined by the
      two assays showed a strong positive correlation (Pearson coefficient 0.82), with
      the ISEL assay detecting twice the number of apoptotic cells as that seen with
      H&E staining. Both assays showed significant interobserver and intraobserver
      variation, while the ISEL assay also showed considerable interassay variability
      and was less cost-effective than H&E in the detection of apoptotic cells.
      CONCLUSION: In the light microscopic quantitation of apoptosis in colorectal
      tumors, the ISEL assay offered no greater reproducibility, and was less cost
      effective, than routine H&E staining.

PMID- 9196806
TI  - Distribution of myosin and actin in moving human neutrophils detected by double
      fluorescence staining.
AB  - OBJECTIVE: To observe the distribution of myosin and actin in the same phase in
      the same human neutrophils with a double-fluorescence staining procedure that
      readily evaluates the association of myosin and actin in human neutrophils during
      movement. STUDY DESIGN: Contractile proteins, consisting mainly of myosin and
      actin, are essential to cell motility. Motile forms of human neutrophils were
      fixed in formaldehyde and glutaraldehyde and stained for fluorescence analysis.
      The prepared slide was first observed with a green filter for fluorescein
      isothiocyanate-labeled antimyosin, with a red filter used for rhodamine-labeled
      phalloidin and without a filter to obtain a phase contrast image. RESULTS: This
      method made it possible to clearly demonstrate the localization of myosin in the
      cytoplasm. The localization of myosin differed from that of actin. The pattern of
      distribution suggested a close association between myosin and actin. Actin was
      reorganized mostly in the filopodia, and myosin was organized in the perigranular
      area. CONCLUSION: Our method utilizes conventional fluorescence microscopy,
      rather than confocal fluorescence microscopy, and was useful for investigating
      the shifts in localization of myosin and actin in the motile forms of such small
      cells as human neutrophils.

PMID- 9196807
TI  - Evaluation of the CytoRich slide preparation process.
AB  - OBJECTIVE: To compare the quality and sensitivity of CytoRich slides with
      conventional cytologic smears and to evaluate the benefits of using this
      technology as an add-on procedure. STUDY DESIGN: The study design consisted of
      non-randomized, paired cervical samples. The subjects were 2,125 Sydney women who
      were routine patients of 13 gynecologists and 8 general practitioners and had
      cytologic smears taken between January and June 1995. All smears were taken using
      the Cervex brush. After preparing the conventional cytologic smear slide, the
      head of the sampler was detached and placed in a vial of fluid fixative. Paired
      slides were then prepared in the laboratory from the cells in the fluid fixative,
      using the CytoRich processing machine. The CytoRich and conventional cytologic
      smear slides were compared for quality, ease of screening, presence of
      endocervical cells, recognition of infections, and detection of squamous and
      glandular abnormalities. RESULTS: CytoRich slides were of much better quality,
      were easier to screen, had substantially fewer unsatisfactory results (0.3% vs.
      2.6%) but lacked endocervical cells more often (16.1% vs. 10.6%). As regards
      abnormalities, the CytoRich slides showed fewer abnormalities, particularly in
      the low grade category. However, as a result of screening the paired CytoRich
      slide, some additional abnormalities were detected and a number of abnormalities
      reported on the conventional slide were reclassified (some to higher grades but
      more to negative). CONCLUSION: As an add-on technology, the CytoRich process has
      much to offer, in particular in the virtual elimination of unsatisfactory smears
      and in helping to resolve the difficult dichotomy between normal and low grade
      categories. Examining additional cellular material on a CytoRich slide enhances
      the sensitivity and accuracy of the combined results.

PMID- 9196808
TI  - Reproducibility of p53 and Ki-67 immunoquantitation in Barrett's esophagus.
AB  - OBJECTIVE: To test the reproducibility and time effectiveness of two
      immunoquantitation and sampling methods in Barrett's esophagus (BE) mucosa. STUDY
      DESIGN: Measurements were performed using image cytometry (CAS 200/486) with "at
      convenience" sampling and stereology (QPRODIT 5.2) with both at convenience and
      systematic random sampling. RESULTS: Quantitation of p53 immunohistochemistry
      (IHC) by CAS was very reproducible by the same observer (r = .99), but its
      interobserver reproducibility was lower, and the measurement was time consuming
      (r = .81, 35 minutes). Moreover, CAS also detected a "signal" in the absence of
      any visually observable brown stain, giving false positive results. Both
      intraobserver and interobserver reproducibility by QPRODIT 5.2 were good. With
      QPRODIT, using systematic random sampling, the measurements were more
      reproducible by different observers and faster (r = .96, 10 minutes) than with
      QPRODIT with at convenience sampling (r = .91, 20 minutes). Therefore, for
      assessment of the Ki-67 labelling index (LI) and area percentage (area%) of Ki-67
      positive nuclei, we used only QPRODIT with systematic random sampling. While
      intraobserver reproducibility of both Ki-67 LI and area% was good (r = .96, r =
      .99), interobserver reproducibility of Ki-67 LI was poorer than area% (r = .72
      vs. r = .97). The assessment of Ki-67 LI was time consuming, whereas the
      measurement of the area% of Ki-67-positive nuclei was very time effective (45 vs.
      7 minutes). A strong correlation was found between Ki-67 LI and area% of Ki-67
      positive nuclei (r = .92). CONCLUSION: Therefore, we conclude that quantitation
      of p53 and Ki-67 IHC in BE mucosa can be very reproducible and highly time
      effective by means of stereology with systematic random sampling.

PMID- 9196809
TI  - Automated molecular genetic DNA analysis for detecting B-cell non-Hodgkin's
      lymphoma in cytologic specimens.
AB  - OBJECTIVE: In fine needle aspiration cytology, conventional morphologic and
      immunocytologic criteria are often insufficient for distinguishing the mixed type
      of follicular lymphoma (NHL) from reactive lymphoid hyperplasia (RLH). For
      improving cytodiagnosis, we adapted computer-assisted polymerase chain reaction
      (PCR) assays on cytologic specimens. These novel techniques aim at fluorescence
      based sequencing and sizing of PCR products that result from NHL-specific
      markers, such as the chromosomal t(14;18) (q32;q21) translocation and the CDR3
      regions of expanded B-cell neoplasia. STUDY DESIGN: Aspirates from eight cases
      with mixed-type follicular NHL and from nine cases with a cytologic finding of
      RLH were investigated by PCR and with an automated laser scanning system.
      RESULTS: PCR detected the t(14;18) translocation in 5/8 B cell NHL samples and
      1/9 RLH samples. By means of automated DNA sequencing, two of the five positive
      probes in the group of NHLs were identified as false positive. The CDR3 regions
      of expanded B-cell clones were found in four of eight NHL aspirates by means of
      PCR and computer-assisted analysis. CONCLUSION: This study proved the reliability
      of automated genetic assays for diagnosing low grade B-cell NHLs in aspirates
      since false positive results are excluded.

PMID- 9196810
TI  - Lymphocyte phenotyping in systemic sclerosis: a flow cytometry analysis of
      lymphocytes in bronchoalveolar lavage fluid.
AB  - OBJECTIVE: Patients with scleroderma (systemic sclerosis [SSc]) frequently
      develop interstitial lung disease. The purpose of this work was to evaluate the
      cell profile in the bronchoalveolar lavage fluid (BALF) in patients suffering
      from a diffuse form of systemic sclerosis as compared with healthy controls.
      STUDY DESIGN: Bronchoalveolar lavage was carried out in the right middle lobe of
      25 untreated, nonsmoking patients with SSc and 12 healthy, nonsmoking volunteers.
      For the analysis of lymphocyte subsets, the following monoclonal antibodies were
      used: anti-CD3, anti-CD4, anti-CD8, anti-CD14, anti-CD16, anti-CD19, anti-CD25,
      anti-CD45, anti-CD56. Also, anti-HLA-DR and flow cytometry were used. RESULTS: We
      found an increase in the total number of cells with an increase in the percentage
      of lymphocytes and neutrophils in BALF from patients when compared with controls
      (P < .05). The proportion of lymphocytes, cytotoxic/suppressor CD8+ and activated
      lymphocytes T CD25+ were higher in patients' BALF (P < .05). The CD4+/CD8+ ratio
      in BALF from subjects was significantly lower than in controls. These findings
      were characteristic of patients with early-stage disease. CONCLUSION: Analysis of
      the BALF lymphocyte phenotype may be useful in the early detection of lung
      involvement in patients with SSc.

PMID- 9196811
TI  - AgNORs in lung cancer: correlation with DNA ploidy and degree of differentiation.
AB  - OBJECTIVE: To assess the usefulness of enumerating argyrophilic nucleolar
      organizer regions (AgNORs) in assisting with the diagnosis, as well as its
      correlation with the degree of differentiation and DNA ploidy, in lung cancer.
      STUDY DESIGN: The specimens, taken from 151 benign and malignant pulmonary
      tumors, were stained with silver nitrate before the number of AgNORs was counted.
      DNA ploidy was determined in 58 cases of lung cancers. All cases of
      adenocarcinoma and squamous cell carcinoma were histologically classified as
      well, moderately or poorly differentiated. RESULTS: Lung cancers had more AgNORs
      than benign tumors, and small cell carcinomas had fewer AgNORs than non-NSCLC (P
      < .001). The mean AgNOR number in adenocarcinoma increased progressively in
      accordance with poorer differentiation (P < .001). There was no correlation
      between the number of AgNORs and DNA ploidy. CONCLUSION: Counting AgNORs helps
      with the differential diagnosis of lung cancers. In adenocarcinoma of the lung,
      the AgNOR number increases as the degree of differentiation decreases.

PMID- 9196812
TI  - Drainage a factor in anthrax outbreak.

PMID- 9196813
TI  - Paroxysmal sneezing in a 7-year-old cat.

PMID- 9196814
TI  - Factor VII deficiency in an Alaskan malamute.

PMID- 9196815
TI  - Prevalences of feline leukaemia virus and feline immunodeficiency virus
      infections in cats in Sydney.
AB  - OBJECTIVE: To determine prevalences of feline leukaemia virus (FeLV) and feline
      immunodeficiency virus (FIV) infections in 'healthy' cats that, through acute
      misadventure or other circumstance, were presented to veterinary practitioners.
      Prevalences of FeLV and FIV in this population were compared to those in a
      population of predominantly sick cats. DESIGN AND PROCEDURES: Serum specimens
      were obtained over a 2-year period from 200 cats older than 1 year of age
      presented to veterinary clinics for routine procedures, including cat fight
      injuries or abscesses, vehicular trauma, neutering, dental scaling, vaccination,
      grooming or boarding. An additional 894 sera were obtained over approximately the
      same period from specimens submitted by veterinarians to a private clinical
      pathology laboratory, mainly from sick cars suspected of having immune
      dysfunction, but including some sera from healthy cats being screened prior to
      FeLV vaccination. FIV antibody and FeLV antigen were detected in samples using
      commercial enzyme immunoassays. RESULTS: Amongst 200 'healthy' cats, the
      prevalence of FeLV infection was 0 to 2%, and the prevalence of FIV was 6.5 to
      7.5%, depending on the stringency of the criteria used to define positivity. FIV
      infection was significantly more prevalent in cats which resided in an inner city
      environment (P = 0.013). Of the 894 serum specimens submitted to the laboratory
      by practitioners, 11/761 (1.4%) were FeLV positive, while 148/711 (20.8%) were
      FIV positive. The prevalence of FIV was significantly higher in these
      predominantly 'sick' cats than in cats seen for routine veterinary procedures (P
      < 0.00001), while there was no difference in the prevalence of FeLV (P = 0.75)
      CONCLUSIONS: The prevalence of FeLV and FIV in healthy cats may have been
      substantially overestimated in some previous Australian surveys. FeLV infection
      would appear to be a rare cause of disease in Australian cats. The higher
      prevalence of FIV positivity in sick as opposed to healthy cats infers that FIV
      infection contributes to the development of disease.

PMID- 9196816
TI  - Acute myelogenous leukaemia in a mare.
AB  - A 5-year-old Thoroughbred mare presented with a 4 week history of weight loss,
      fever and leukopenia. Rectally, a large active foetus, thickened spleen and an
      abdominal mass were palpated. Leukopenia, mild anaemia, marked thrombocytopenia
      and hyperfibrinogenaemia were found. Cytology and cytochemical staining of a bone
      marrow aspirate supported a diagnosis of acute myelogenous leukaemia. The mare
      deteriorated despite medical therapy and was humanely euthanased.

PMID- 9196817
TI  - Nonsurgical treatment of chondroids of the guttural pouch in a horse.

PMID- 9196818
TI  - Monorchidism in two horses.

PMID- 9196819
TI  - Can Johne's disease be eradicated from sheep in Australia?

PMID- 9196820
TI  - Effect of breed of cattle on innate resistance to infection with Babesia bovis, B
      bigemina and Anaplasma marginale.
AB  - OBJECTIVE: To assess the innate resistance of naive Bos taurus, Bos taurus cross
      Bos indicus and Bos indicus cattle to virulent Babesia bovis, B bigemina and
      Anaplasma marginale parasites. DESIGN: Groups of 10, pure B indicus, 1/2 B
      indicus cross, 1/4 B indicus cross and pure B taurus steers were infected with
      virulent B bovis, B bigemina and A marginale parasites [corrected]. PROCEDURE:
      Sequential infections were carried out by intravenous inoculation of infected
      blood containing 1 x 10(8) parasites of B bovis, followed by B bigemina and then
      A marginale. To assess resistance, measurements were made of parasitaemia, rectal
      temperature, packed cell volume and the number within a group requiring
      chemotherapy to control infection. There was a recovery period between each
      infection. RESULTS: Infection with B bovis showed that pure B indicus steers were
      significantly more resistant to B bovis infection than the other groups, with
      none of this group requiring treatment. There was no significant difference
      between 1/2 B indicus cross and 1/4 B indicus cross with 30% and 20%,
      respectively, of steers in these groups requiring treatment [corrected]. The pure
      B taurus steers were significantly more affected then those in the other three
      groups with 80% requiring treatment. Infections of B bigemina produced a mild
      response in comparison to that of B bovis and none of the steers required
      treatment. However, the pure B taurus group was significantly more affected than
      the other three groups for all other measurements. After the A marginale
      infection, B indicus steers were moderately affected with 50% requiring
      treatment, whereas 70% of the 1/2 B indicus group, 80% of the 1/4 B indicus cross
      group and 100% of the pure B taurus group required treatment [corrected].
      CONCLUSIONS: All breeds of cattle, ranging from pure B indicus to pure B taurus
      may be at risk of severe disease if exposed to virulent A marginale. The results
      confirm that pure B indicus cattle are relatively resistant to B bovis, but there
      could be a significant risk of severe mortalities if cross-bred herds are exposed
      to virulent infection.

PMID- 9196821
TI  - Effectiveness of alpha-tocopherol and selenium supplements in preventing
      lupinosis-associated myopathy in sheep.
AB  - OBJECTIVE: To compare the effectiveness of combined selenium and alpha-tocopherol
      acetate treatments in preventing lupinosis-associated myopathy in sheep. DESIGN:
      Measurement of plasma muscle and liver enzymes, and histopathological examination
      of muscle and liver in the treatment groups. PROCEDURE: The treatments were:
      subcutaneous injections of selenomethionine and vitamin E (sc(SeM+E)), an
      intraruminal selenium pellet and oral doses of vitamin E and intramuscular
      injections of selenomethionine combined with either oral doses of vitamin E
      (imSeM+orE) or intramuscular injections of vitamin E in an oily carrier. Another
      group received no supplements, while a control group was given selenium pellets
      on day 0 and fortnightly oral doses of vitamin E from day 0 to 72. To produce
      lupinosis-associated myopathy, the sheep were fed a diet low in vitamin E and
      given repeated injections of a crude extract of Diaphorthe toxica. Groups
      sc(SeM+E) and imSeM+orE were stressed by dosing with protected polyunsaturated
      fatty acids from day 56 onwards. RESULTS: Lupinosis-associated myopathy was
      induced in all unsupplemented sheep. In these sheep the storage of Se increased
      and that of vitamin E decreased. The subcutaneous treatment was highly effective
      in preventing lupinosis-associated myopathy and also produced the highest vitamin
      E concentrations in plasma and liver. Supplemental vitamin E was more efficacious
      than supplemental Se. Concentrations of vitamin E in the livers of sheep given
      intramuscular vitamin E were higher than expected based on plasma concentrations.
      Oral doses of vitamin E proved the least effective method of increasing
      concentrations in liver. Lupinosis did not affect Se concentrations in liver or
      muscle. CONCLUSION: The sc(SeM+E) treatment is highly effective in preventing
      lupinosis-associated myopathy but needs to be further assessed when selenium and
      vitamin E are both limiting in the diet.

PMID- 9196822
TI  - Occurrence of cutaneous infections of Myxobolus episquamalis
      (Myxozoa:Myxobolidae) in sea mullet, Mugil cephalus L, in Australia.
AB  - OBJECTIVE: To report the occurrence of Myxobolus episquamalis in sea mullet,
      Mugil cephalus L, caught in estuaries in eastern and western Australia. DESIGN: A
      prospective study of commercial catches of mullet in the Clarence River of NSW
      and individual cases from other areas. RESULTS: The organism caused pale, white
      to pink, raised lesions on the scales and fins of sea mullet. Occurrence of
      infection was highest in spring and in a marine (down-river) environment compared
      to a brackish environment. Up to 6% of fish were affected in commercial catches.
      CONCLUSION: The infection is widespread in Australian mullet, but rarely causes
      significant economic loss.

PMID- 9196823
TI  - Comparison of erythromycin and oxytetracycline for the treatment of virulent
      footrot in grazing sheep.

PMID- 9196824
TI  - Antimicrobial resistance in Salmonella and Escherichia coli isolated from horses.

PMID- 9196825
TI  - Ulcerative dermatitis associated with Uronema sp infection of farmed sand whiting
      Sillago ciliata.

PMID- 9196826
TI  - Disseminated zygomycosis caused by Conidiobolus incongruus in a deer.

PMID- 9196827
TI  - Depression of staple strength in weaner sheep supplemented with copper.

PMID- 9196828
TI  - Poisoning of feedlot cattle by seeds of Heliotropium europaeum.

PMID- 9196829
TI  - Confirmed histoplasmosis in an Australian dog.

PMID- 9196830
TI  - Cerebellar degeneration in goats grazing Solanum cinereum (Narrawa burr).

PMID- 9196831
TI  - Isolation of Dermatophilus sp from skin lesions in farmed saltwater crocodiles
      (Crocodylus porosus).

PMID- 9196833
TI  - Who are we treating?

PMID- 9196832
TI  - Australian bat lyssavirus.

PMID- 9196834
TI  - Action on preservatives in fresh pet food.
AB  - In late 1995 and early 1996, Sydney vet Dr Bob Steel reported first-hand
      experience with a cat dying from thiamine deficiency. This deficiency was
      attributable to the presence of sulfur dioxide in fresh pet food which was fed to
      the cat over a period of time. The diagnosis was confirmed, as was the presence
      of sulfur dioxide in significant levels. Since that time, Dr Steel and the AVA
      have pursued the issue of preservatives (specifically those producing sulfur
      dioxide) in fresh pet food. An update on that work follows.

PMID- 9196835
TI  - New induction agents.

PMID- 9196836
TI  - Alpha-2 adrenergic agonists.

PMID- 9196837
TI  - Nitric oxide and related vasodilators.

PMID- 9196838
TI  - Anaesthesia for neuroradiology.

PMID- 9196839
TI  - Sedation, analgesia and muscle relaxation and the critically ill patient.

PMID- 9196840
TI  - Anaesthesia and analgesia in the emergency department.

PMID- 9196841
TI  - The myocardium.

PMID- 9196842
TI  - The patient with reactive airways disease.

PMID- 9196843
TI  - Anaesthesia for carotid artery surgery.

PMID- 9196844
TI  - The drug addicted patient.

PMID- 9196845
TI  - Discontinuing drugs before surgery.

PMID- 9196846
TI  - Awareness during general anesthesia.

PMID- 9196847
TI  - Public relations in anaesthesia.

PMID- 9196848
TI  - Acute pain--guidelines for care.

PMID- 9196849
TI  - Adverse reactions to food constituents: allergy, intolerance, and autoimmunity.
AB  - Food allergies and intolerance represent important health concerns to consumers
      who are predisposed to these illnesses. Unlike many current food safety issues,
      food sensitivities are complicated by both complex and multiple individual
      adverse reactions, which can vary from emotional to pathophysiological ailments.
      In some instances, the underlying mechanisms that result in the development of
      food allergies or intolerance have marked differences but produce common
      symptoms. The present-day diagnosis of these disorders can be impeded by
      intrinsic limitations in generating accurate information from patient history and
      biochemical, physicochemical, and immunochemical tests. Oral challenge tests
      represent effective methods for confirming and testing food allergens and food
      intolerance; however, these procedures are often restricted to clinical trials.
      It is important to be able to distinguish among food allergy, intolerance, and
      autoimmune disease in the management of these disorders. The role of food in the
      development of autoimmune disease may be exemplified by celiac disease, a food
      induced enteropathy, requiring exposure to prolamins in wheat, rye, and barley.
      Various wheat and soy protein sources, including the soy protein isolates used to
      make infant formulas, have been related to juvenile or insulin-dependent diabetes
      mellitus (IDDM), a common chronic disease of childhood. Employing food process
      technologies to eliminate food constituents with potential for intolerance in
      some individuals is a potentially viable approach for reducing risk to food
      related disorders. Finally, the development of food labelling regulations that
      require the identification of potential food allergens or agents for intolerance
      in the ingredient declaration on prepackaged food is a positive step toward the
      prevention of severe adverse reactions in hypersensitive individuals.

PMID- 9196850
TI  - Characteristics of restitution kinetics in repolarization of rabbit atrium.
AB  - The study was designed to characterize restitution kinetics in atrial
      repolarization of rabbits and to examine effects of K+ or Ca2+ channel blockers
      on restitution. Action potentials were recorded from rabbit atrial tissue.
      Restitution curves of phase I amplitude and action potential duration at 50 and
      90% repolarization (APD50, APD90) were defined at a basic cycle length of 0.5 s
      during control and with interventions. Restitution of phase I amplitude had a
      monoexponential function with a time constant of 2.8 +/- 0.2 s. The curves of
      APD50 frequently had a monoexponential function and time constants were 1.8 +/-
      0.1 s. Restitution curves of APD90 were biphasic: a descending phase followed by
      an ascending phase. The blocker of Ito1 (a 4-aminopyridine-sensitive component of
      the transient outward current), 4-aminopyridine, flattened the restitution curves
      of phase I amplitude, and APD50 and APD90 curves became monophasic. Sotalol, a
      selective IKr (a rapid component of the delayed rectifier K+ current) blocker,
      did not alter curves of phase I amplitude and APD50 but shifted APD90 curves
      upward. Cadmium, a Ca2+ blocker shifted curves of phase I amplitude and APD50
      downward and abolished the ascending phase of APD90 curves. We conclude that
      kinetics of Ito1 and ICa (calcium current) may account for characteristics of
      restitution of atrial repolarization in rabbit.

PMID- 9196851
TI  - Effects of the angiotensin converting enzyme (ACE) inhibitor, captopril, on the
      cardiovascular, endocrine, and renal responses to furosemide in conscious lambs.
AB  - To test the hypothesis that angiotensin II modulates the physiological responses
      to furosemide in the newborn, various parameters of cardiovascular, renal, and
      endocrine function were measured before and after iv injection of furosemide to
      eight conscious, chronically instrumented lambs in the presence and absence of
      the angiotensin converting enzyme (ACE) inhibitor, captopril. During ACE
      inhibition, the rise in heart rate and decrease in renal blood flow in response
      to furosemide did not occur, and the natriuretic and diuretic responses to
      furosemide were attenuated by approximately two-thirds. There was also an
      increase in the urinary excretion of prostaglandin F2 and prostaglandin F1 alpha
      as well as an increase in the excretion of prostaglandin E2 after furosemide, in
      the presence of ACE inhibition. Therefore, the cardiovascular, renal, and
      endocrine responses to furosemide in conscious lambs were significantly altered
      by ACE inhibition.

PMID- 9196852
TI  - Thromboxane A2 acts at a site perfused by the carotid vasculature to mediate
      cardiovascular and adrenocortical responses.
AB  - Increases in thromboxane A2 (TxA2) synthesis are associated with hemodynamic
      responses and activation of the hypothalamus-pituitary-adrenal axis. This study
      tested the hypothesis that TxA2 acts on a site perfused by the carotid
      vasculature to mediate these responses. The TxA2 mimetic U46619 was infused for
      30 min into the carotid artery or the vena cava of chronically instrumented adult
      sheep at doses of 0, 0.25, 0.5, and 1.0 microgram.kg-1.min-1. Mean arterial
      pressure increased in response to carotid or vena cava U46619 infusions of 0.5
      and 1.0 microgram.kg-1.min-1. Heart rate was elevated in response to carotid (0.5
      and 1.0 microgram.kg-1.min-1) or vena cava (1.0 microgram.kg-1.min-1) infusions
      of U46619. Paco2 declined and pH2 increased significantly in response to carotid
      infusions of 0.5 and 1.0 microgram.kg-1.min-1 but did not change in response to
      vena cava infusions. Adrenocorticotropic hormone (ACTH) increased in response to
      carotid infusions of 0.5 microgram.kg-1.min-1, while cortisol increased in
      response to infusions of 0.25, 0.5, and 1.0 microgram.kg-1.min-1. ACTH and
      cortisol did not change in response to vena cava infusions. Pao2, hematocrit, and
      arginine vasopressin did not change significantly. Pulmonary artery pressure and
      total peripheral resistance increased while cardiac output decreased in response
      to carotid or vena cava U46619 infusions of 1 microgram.kg-1.min-1; carotid and
      vena cava responses were not different from one another. We conclude that
      increases in blood pressure are mediated by peripheral PGH2/TxA2 receptor
      activation and that pituitary adrenal, blood gas, and heart rate responses are
      mediated by PGH2/TxA2 receptor activation at a site perfused by the carotid
      vasculature.

PMID- 9196853
TI  - Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced
      relaxation of rat pulmonary and celiac artery rings.
AB  - The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine
      methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat
      intrapulmonary artery and celiac artery ring segments was studied in vitro with
      and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME,
      raised baseline tone more in pulmonary than celiac arteries. Pretreatment of
      pulmonary and celiac artery rings with meclofenamate did not alter this
      contractile effect. Pulmonary artery and celiac artery ring segments were
      precontracted with phenylephrine, and cumulative concentration-relaxation curves
      to ACh were obtained before and after incubation of the rings with L-NAME or L
      NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at
      10000 fold lower concentrations than those needed to only partly inhibit the ACh
      induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the
      ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent
      manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced
      relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L
      NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery
      rings were pretreated with meclofenamate (1.0 microM). These results suggest that
      in the pulmonary artery nitric oxide plays a greater role in the modulation of
      baseline vascular tone and ACh-induced relaxation than in the celiac artery. In
      addition, cyclooxygenase products do not contribute to the direct contractile
      responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but
      do modulate the ACh-induced relaxation of these vessels.

PMID- 9196854
TI  - Modulation of intestinal paracellular permeability by intracellular mediators and
      cytoskeleton.
AB  - The influence of cytoskeletal inhibitors (cytochalasin E and colchicine) and
      intracellular mediators (cAMP, Ca2+, and protein kinase C) in the control of
      paracellular permeability to mannitol has been examined in rat jejunum in Ussing
      type chambers. Cytoskeletal inhibitors, cytochalasin E (20 mumol.L-1) or
      colchicine (0.5 mmol.L-1), when present in mucosal, serosal, or in both mediums,
      significantly increase unidirectional mannitol fluxes. Exposure of mucosal and
      serosal intestinal surface to 10 mmol.L-1 theophylline or 1 mmol.L-1 cyclic AMP
      analogue for raising the intracellular cAMP enhances paracellular permeability.
      In Ca(2+)-free physiological medium passive permeability strongly increases.
      Alterations of cytosolic Ca2+ levels induced by the Ca2+ ionophore A23187 (20
      mumol.L-1) or by 0.3 mmol.L-1 TMB-8, a Ca2+ releasing inhibitor from the
      intracellular stores, enhance mannitol flux. Addition of the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate, which activates protein kinase C (PKC), also
      induces a large increase in the intestinal permeability to mannitol. These
      results provide evidence that tight junctions and consequently epithelial
      paracellular permeability can be physiologically controlled by intracellular
      mediators (Ca2+, cAMP, and PKC) probably through modulation of the cytoskeleton
      activity.

PMID- 9196855
TI  - Effect of magnesium on vascular tone and reactivity in pressurized mesenteric
      resistance arteries from spontaneously hypertensive rats.
AB  - This study examines the effects of magnesium on vascular tone and reactivity in
      mesenteric resistance arteries from 17-week-old spontaneously hypertensive rats
      (SHR) and Wistar-Kyoto rats (WKY). Third-order branches of mesenteric arteries
      were mounted in a pressurized flow chamber and studied with constant flow and
      transmural pressure. The mesenteric arteries were perfused extra- and intra
      luminally with physiological salt solution containing a normal (1.2 mmol/L), high
      (4.8 mmol/L), or low (0.15 mmol/L) magnesium concentration. Vascular reactivity
      to norepinephrine and vasopressin was examined when the agonists were applied
      extraluminally. High magnesium increased lumen diameter and decreased media
      thickness whereas low magnesium decreased lumen diameter and increased media
      thickness in mesenteric arteries from both SHR and WKY rats. The effects of
      magnesium on vascular tone were less in arteries from SHR compared with
      normotensive controls (p < 0.05). Low magnesium potentiated norepinephrine
      induced vasoconstriction in SHR (p < 0.001) but not in WKY. Low magnesium did not
      modify vasopressin-induced vasoconstriction in either SHR or WKY. High magnesium
      attenuated vasopressin- and norepinephrine-induced vasoconstriction in SHR (p <
      0.01), whereas high magnesium attenuated only norepinephrine-induced
      vasoconstriction in WKY (p < 0.001). These data suggest that magnesium has
      differential modulatory effects on vascular tone and reactivity in mesenteric
      resistance arteries of SHR and WKY. Magnesium may play an important role in the
      modulation of peripheral resistance in hypertension.

PMID- 9196856
TI  - Salivary kallikrein output during the stress response to surgery.
AB  - Sixteen adult humans (American Surgical Association, grade I-II) scheduled for
      elective hysterectomy and (or) oophorectomy with general anesthesia for benign
      disease were the subjects in this study of the output of kallikrein into the
      saliva during the stress response to surgery. Saliva samples for salivary
      kallikrein output determination and plasma for cortisol estimates were collected
      before and at several times after surgery. Subjective reports of pain were also
      recorded. Salivary kallikrein output was significantly elevated over preoperative
      levels at 2, 4, and 6 h following surgery and reached a level at 4 h that was 8
      times higher than preoperative levels. All subjects experienced a stress
      response, as indicated by elevated levels of plasma cortisol, and all reported
      postoperative pain. The results indicate that increased salivary kallikrein
      output is associated with the stress response to surgery.

PMID- 9196857
TI  - Pharmacology of ATP-sensitive potassium channel (KATP) openers in models of
      myocardial ischemia and reperfusion.
AB  - Recently, much interest has been focused on the pharmacology of ATP-sensitive
      potassium channels (KATP) in myocardial ischemia. KATP are thought to be involved
      with the mechanism of myocardial preconditioning, therefore further increasing
      the level of interest in these channels. Pharmacologic KATP openers have been
      shown by numerous investigators to protect ischemic-reperfused myocardium. These
      agents reduce necrosis, improve postischemic functional recovery, and inhibit
      contracture formation. These protective effects are abolished by KATP blockers.
      The cardioprotective effects of KATP openers are independent of vasodilator and
      cardiodepressant effects, but seem to be mediated by energy conservation (reduced
      ATP hydrolysis). Action potential shortening is also not correlated with
      cardioprotection, suggesting a role for intracellular (mitochondrial) KATP.
      Agents have been developed that retain the glyburide-reversible cardioprotective
      effects of cromakalim but are devoid of vasodilator and action potential
      shortening activity. Currently, studies are underway to determine the mechanism
      of cardioprotection. The potential role of mitochondrial KATP in the pathogenesis
      of ischemia is discussed in this review article.

PMID- 9196858
TI  - Cardioprotection induced by ischemic preconditioning in the mammalian heart:
      effects on arrhythmogenesis.
AB  - Ischemic preconditioning (PC) describes the protection that occurs when a brief
      period of ischemia increases the tolerance of the heart to a future ischemic
      episode of longer duration. This protection is typically measured as a reduction
      in myocardial infarct size or improved recovery of contractile function. Few
      studies have tested whether PC also prevents the occurrence of severe
      arrhythmias, such as ventricular tachycardia (VT) and fibrillation (VF). We
      studied the effects of preconditioning on arrhythmias in Langendorff-perfused
      rabbit hearts. All hearts were subjected to a 30-min test ischemia followed by
      reperfusion. Preconditioned hearts underwent one to four ischemic periods (5 min
      each, separated by 10 min of reperfusion) 30 min prior to the test ischemia. VF
      occurred in 42% of non-PC hearts during ischemia. One PC period totally
      suppressed VF (0%; p < 0.05) and two PC periods provided partial protection (VF =
      17%). In contrast, 64 and 50% of hearts receiving three or four PC periods
      fibrillated during ischemia, respectively. The test ischemia induced an ischemic
      contracture that was prevented by two or three PC periods, but not one or four PC
      periods. None of the PC protocols improved postischemic contractile recovery. In
      conclusion, our data show that a single PC period completely protects against
      ischemia-induced VF in rabbit hearts. Preconditioning also prevents development
      of an ischemic contracture. However, the optimal preconditioning "dose" that
      prevents arrhythmias is not the same as that which protects against contractile
      dysfunction.

PMID- 9196859
TI  - Effect of sodium-hydrogen exchange inhibition on functional and metabolic
      impairment produced by oxidative stress in the isolated rat heart.
AB  - Sodium-hydrogen exchange (NHE) represents an important process mediating
      myocardial ischemic and reperfusion injury, and NHE inhibitors have been shown to
      be effective cardioprotective agents against this form of injury. The precise
      mechanisms by which NHE inhibition protect the heart are not known and we
      therefore postulated that attenuation of oxidative stress could contribute to
      such protection. Accordingly, we examined whether the potent and specific NHE
      inhibitor 4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate (HOE
      642, 5 microM) can protect isolated rat hearts against mechanical and biochemical
      impairment produced by either hydrogen peroxide (150 or 200 microM) or a free
      radical generating system consisting of purine (4.6 or 9.2 mM) and xanthine
      oxidase (20 or 40 U/L). HOE 642 significantly delayed and attenuated both the
      depression in left ventricular developed pressure (LVDP) as well as the elevation
      in left ventricular end-diastolic pressure (LVEDP) produced by both
      concentrations of hydrogen peroxide, although greater protection was generally
      seen against the lower hydrogen peroxide concentration, particularly with respect
      to LVEDP. Hydrogen peroxide, at both concentrations, significantly reduced high
      energy phosphate and glycogen contents and elevated lactate levels, all of which
      were significantly attenuated by HOE 642. In contrast, HOE 642 had no effect on
      functional impairment produced by either concentration of the free radical
      generating system. At its lower concentration, the combination of purine plus
      xanthine oxidase had no effect on energy metabolites, although a significant
      reduction in high energy phosphate stores was seen with the higher concentration.
      However, this was unaffected by HOE 642. The protective effect of HOE 642 was
      mimicked by another NHE inhibitor, methylisobutylamiloride (MIA, 5 microM). Our
      study therefore shows that NHE inhibition selectively protects against functional
      and metabolic impairment produced by hydrogen peroxide. Since hydrogen peroxide
      formation has been implicated in the development of ischemic and reperfusion
      injury, it is possible that the protective effect of NHE inhibition against this
      form of oxidative stress may explain in part the basis for the well-established
      salutary actions of NHE inhibitors in the ischemic and reperfused myocardium.
      Since HOE 642 failed to modify the response to free radical generators, it is
      unlikely that the protective effects of NHE inhibitors can be explained by a free
      radical scavenging mechanism.

PMID- 9196860
TI  - Different preconditioning stimuli invoke disparate electromechanical and
      energetic responses to global ischemia in rat hearts.
AB  - One hypothesized mechanism of the cardioprotection provided by preconditioning is
      decreased utilization of ATP during ischemia. Although ATP levels in
      preconditioned heart during ischemia have been previously studied, contractile
      activity during ischemia has not been investigated. Contractile activity accounts
      for significant ATP consumption during ischemia. We hypothesized that
      preconditioning stimuli may conserve energy during the ischemic period by
      decreasing myocardial contractile energy expenditure prior to asystolic cardiac
      arrest. We studied three preconditioning stimuli: (i) four cycles of 5-min
      periods of ischemia (4 x 5' CI), (ii) 2 min of alpha 1-adrenergic stimulation
      (phenylephrine; PE), and (iii) 2 min of P1-purinergic stimulation (adenosine).
      The effects of these stimuli on myocardial ATP, ventricular contractility, and
      the time to cessation of electromechanical function (asystole) during the
      sustained ischemic period were then examined. Preconditioning stimuli (4 x 5' CI,
      phenylephrine, and adenosine) improved postischemic functional recovery compared
      with nonpreconditioned controls. Myocardial ATP contents at the end of 20 min of
      global ischemia were higher for adenosine-treated (9.0 +/- 1.5 mumol/g dry
      weight; p < 0.05) and PE-treated (9.9 +/- 1.9 mumol/g dryweight; p < 0.05) hearts
      than for controls (6.6 +/- 1.2 mumol/g dry weight). The CI hearts began with
      lower myocardial ATP levels (9.9 +/- 1.2 mumol/g dry weight; p < 0.05) than other
      groups prior to the sustained ischemic period (control 13.4 +/- 1.0 mumol/g dry
      weight). As a result of a lower rate of ATP depletion, ATP levels in the CI group
      were similar to the untreated control after 20 min of sustained ischemia (5.5 +/-
      0.7 mumol/g dry weight). Preconditioning with 4 x 5' CI or adenosine (but not PE)
      led to earlier ventricular arrest. Only adenosine-treated hearts demonstrated a
      more rapid decline in ventricular contractility during sustained ischemia than
      did nonpreconditioned control hearts. We conclude that while the final recovery
      of ventricular contractility after asystolic arrest and reperfusion is improved
      by preconditioning with different stimuli (4 x 5' CI, adenosine, or PE), each
      stimulus conferred a characteristic electromechanical and energy conservation
      strategy during sustained ischemia. Adenosine conserved myocardial ATP content
      and reduced total cardiac work (developed pressure and heart beats). CI conserved
      myocardial ATP and minimized the number of ischemic cardiac beats. PE preserved
      myocardial ATP during ischemia without changing contractile behavior. Thus,
      energy conservation strategies during ischemia could contribute to the protection
      afforded by preconditioning stimuli, but the mechanisms appear to differ among
      stimuli.

PMID- 9196861
TI  - Cardiovascular dysfunction in insulin-dependent and non-insulin-dependent animal
      models of diabetes mellitus.
AB  - Morbidity in the diabetic population is primarily a result of cardiovascular
      dysfunction and failure. Ischemic heart disease is a serious complication in the
      diabetic population. Recent data indicate that hearts from insulin-dependent
      models of diabetes differ significantly in their response to ischemia from hearts
      of models of non-insulin-dependent diabetes. Intrinsic cardiac factors may be
      responsible for the altered sensitivities to ischemia in the different types of
      diabetes. However, vascular dysfunction is also clearly present in the diabetic
      animal models. Endothelial cell damage and dysfunction play a prominent role in
      the contractile abnormalities and lesion formation during diabetes. The present
      treatise focuses upon insulin as a causative factor in cardiovascular disease and
      the differences between insulin-dependent and non-insulin-dependent models of
      diabetes.

PMID- 9196862
TI  - Life events in the course of chronic diseases: a psychological myth or a psycho
      neuro-biochemical loop?

PMID- 9196863
TI  - Morphological aspects of giant cells in giant cell arteritis: an electron
      microscopic and immunocytochemical study.
AB  - OBJECTIVES: To compare the morphology of foreign body and Langhans giant cells in
      the two different inflammatory phases of giant cell arteritis (GCA). METHODS:
      Electron microscopy was performed on 6 positive temporal arterial biopsies. Light
      microscopy and immunocytochemistry for macrophage-associated antigen (KP1) and
      alpha-smooth muscle actin (alpha-SMA) were performed on 16 positive biopsies.
      RESULTS: A focal granulomatous reaction with foreign body giant cells was found
      only in association with the internal elastic membrane (IEM) in atrophic arterial
      segments, which often displayed calcification of the IEM. Diffuse invasion of
      lymphocytes and monocytes/macrophages affected non-atrophic as well as atrophic
      arterial segments. Within such segments Langhans giant cells were found in all
      layers of the wall. Electron microscopy of biopsies displaying the focal foreign
      body reaction revealed that large cells devoid of lysosomes but with cytoplasmic
      densities, tightly packed cytoplasmic filaments and numerous micropinocytotic
      vesicles formed clusters close to calcified parts of the internal elastic
      membrane. Furthermore, foreign body giant cells were surrounded by large cells
      devoid of lysosomes. Lysosomes tended to concentrate in central parts of the
      foreign body giant cells. In the diffusely inflamed arteries, the Langhans giant
      cells were surrounded by mononuclear cells rich in lysosomes. The lysosomes in
      the Langhans giant cells were more evenly distributed than in foreign body giant
      cells. Immunocytochemistry of biopsies displaying the focal granulomatous
      reaction revealed an uneven, often central immunoreactivity for the macrophage
      marker (KP1) in the foreign body giant cells, and immunostaining for alpha-smooth
      muscle antigen (alpha-SMA) showed their poor delineation from the surrounding
      vascular smooth muscle cells. The Langhans giant cells in the diffusely inflamed
      arteries displayed a strong even cytoplasmic immunoreactivity for KP1 and a
      distinct delineation from the smooth muscle cells in the alpha-SMA staining.
      CONCLUSION: Differences in terms of distribution, light microscopy,
      immunocytochemistry and electron microscopy between the two types of giant cells
      in GCA indicate a difference in their function as well as their histogenesis.

PMID- 9196864
TI  - Cytokine production in scleroderma patients: effects of therapy with either
      iloprost or nifedipine.
AB  - OBJECTIVE: To compare the long-term effects of intermittent infusion of iloprost
      with those of oral nifedipine on the in vitro production of cytokines in patients
      with systemic sclerosis (SSc), and to evaluate their relationship with the
      effects of the two treatments on clinical parameters. METHODS: The production of
      cytokines by alloactivated circulating mononucleated cells was assessed before
      and after one year of treatment in a subset of 31 patients enrolled in a 12-month
      randomized clinical trial. Nineteen patients were treated with a 5-day (8 hr per
      day), 2.0 ng/kg per minute infusion followed by a 1-day infusion every 6 weeks;
      12 patients were treated with an oral slow-release formulation of nifedipine, 20
      mg twice daily. Quantitative determinations of interleukin-1 beta (IL1-beta) and
      interleukin-6 (IL6) in the culture supernatants were performed with a commercial
      ELISA; the levels of tumor necrosis factor-alpha (TNF-alpha), and interferon
      gamma (IFN-gamma) were measured by specific radioimmunometric assays. RESULTS:
      The production of IL1-beta was significantly lower in the iloprost group than in
      the nifedipine group. Both the cutaneous fibrosis and the capillaroscopic
      patterns were better in patients treated with iloprost than in patients treated
      with nifedipine. There was a significant positive covariance between IL1-beta
      changes and the changes in both the skin score and the capillaroscopic score.
      CONCLUSION: There are several mechanisms by which iloprost could exert its
      clinical efficacy. Vasodilatation and inhibition of platelet aggregation are
      certainly important, but they are transient. We suggest that the long-lasting
      modulation of the cytokine network observed in the present study could be another
      potential mechanism responsible for the persistent efficacy of iloprost despite
      its intermittent administration.

PMID- 9196865
TI  - Isotype distribution and clinical significance of antibodies to cardiolipin,
      phosphatidic acid, phosphatidylinositol and phosphatidylserine in systemic lupus
      erythematosus: prospective analysis of a series of 92 patients.
AB  - OBJECTIVE: To determine the prevalence and correlation with clinical
      manifestations of the IgG and IgM isotypes of antibodies to cardiolipin (aCL),
      phosphatidic acid (aPA), phosphatidylinositol (aPI) and phosphatidylserine (aPS)
      in patients with systemic lupus erythematosus (SLE). METHODS: Clinical and
      laboratory features of 92 consecutive unselected patients with SLE were
      prospectively studied over two years. aCL, aPA, aPI and aPS were determined by
      ELISA. RESULTS: aCL were detected in 34 (37%) patients, aPA in 26 (28%), aPI in
      22 (24%), and aPS in 29 (32%). A significant association was found between the
      appearance of thrombosis and the presence of IgG aCL (p < 0.001) and IgG aPS (p <
      0.05). A significant association was also found between thrombocytopenia and the
      presence of IgG aCL (p < 0.001), IgG aPA (p < 0.01), IgG aPI (p < 0.05), and IgG
      aPS (p < 0.001). The development of hemolytic anemia was associated with the
      detection of IgM aCL (p < 0.001), IgM aPA (p < 0.05), IgM aPI (p < 0.001), and
      IgM aPS (p < 0.01). CONCLUSION: We found a relatively high prevalence of aCL,
      aPA, aPI and aPS in our SLE population and confirmed the presence of a
      correlation between the IgG isotype of these antibodies and thrombosis and
      thrombocytopenia, and also between the IgM isotype and hemolytic anemia. These
      results demonstrate the variety of antiphospholipid antibodies that can be
      detected in SLE patients, as well as their association with the clinical
      manifestations of the antiphospholipid syndrome.

PMID- 9196867
TI  - Practical usefulness of IgA-containing immune complex determination in the serum
      of patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To evaluate the relevance of IgA-containing immune complexes (IC) as a
      predictor of lymphocytic infiltration of the minor salivary glands, and thus to
      determine the necessity of the minor salivary gland biopsy as a diagnostic test
      for primary Sjogren's syndrome (SS) in patients complaining of dryness of the
      mouth. METHODS: IgA-containing IC, as well as anti-SSA and anti-SSB antibodies,
      were measured using enzyme-linked immunosorbent assays in 116 consecutive
      patients presenting with dry mouth but no connective tissue disease. The
      specificity, sensitivity, and positive (PPV) and negative predictive values (NPV)
      of these tests were calculated in relation to the results of the minor salivary
      gland biopsy and to the criteria for primary SS. RESULTS: Sixty-five patients had
      a focus score > or = 1.IgA-containing IC were detected in 45 of them, compared
      with five of the remainder (specificity 89%, sensitivity 69%, PPV = 88% and NPV =
      69%). When the IgA-containing IC, and the anti-SSA and anti-SSB tests were
      associated, the sensitivity and NPV were improved (81 and 79%, respectively),
      while specificity and PPV were maintained (88 and 90%, respectively). CONCLUSION:
      Given the reliability of this combination of tests for the diagnosis of primary
      SS, the minor salivary gland biopsy might be indicated only in those patients
      without any serological abnormality.

PMID- 9196866
TI  - Contrast enhanced Gd-DTPA magnetic resonance imaging in the evaluation of
      rheumatoid arthritis during a clinical trial with DMARDs. A prospective two-year
      follow-up study on hand joints in 31 patients.
AB  - OBJECTIVE: The aim of this prospective 24-month follow-up study was to compare
      clinical features with radiological and magnetic resonance imaging (MRI) findings
      in evaluating synovial proliferation in the hand joints of 31 patients with
      rheumatoid arthritis (RA). A single joint was used for the follow-up of each
      patient. METHODS: Thirty-one small hand joints were examined by conventional
      radiography and MRI before and after 24 months of treatment. MRI assessment of
      disease progression (volume and/or signal intensity of the synovial proliferation
      on T1 weighted precontrast, T1 weighted postcontrast and T2 weighted images) was
      compared with a clinical assessment of the chosen joints, and with a plain x-ray
      film evaluation (Larsen's score). RESULTS: Of 26 joints which clinically improved
      (14 markedly and 14 slightly) during the study, on MRI 16 showed improvement, 8
      showed no change, and 2 showed deterioration. Four clinically unchanged joints
      appeared improved on MRI. One joint deteriorated clinically and on MRI. Overall,
      there was a 58% congruence between clinical and MRI findings. On x-ray 23 joints
      showed no change; nine of these were also unchanged on MRI, while 13 showed
      improvement and one deterioration. Only in 2 out of 8 joints showing
      deterioration on x-ray were the MRI findings in accordance. In the remaining six
      joints MRI showed improvement. The congruence between x-ray and MRI was therefore
      36%. CONCLUSION: The long-term follow-up of rheumatoid synovial proliferation of
      the small joints in the hand using contrast enhanced MRI is feasible and may
      provide additional information regarding disease activity. Important advantages
      over conventional radiography methods are its ability to demonstrate qualitative
      differences of synovial proliferation within bone erosions, and demonstrate not
      only deterioration, but also the improvement of inflammatory disease.

PMID- 9196868
TI  - Effect of cytokines on the production of endothelin by endothelial cells.
AB  - OBJECTIVE: Circulating levels of endothelin (ET), a potent vasoconstrictor
      peptide and a mitogen for smooth muscle cells and fibroblasts, are reported to be
      increased in a variety of human diseases characterized by vascular pathology. In
      view of the probable immune bases for vascular injury in connective tissue
      disorders, we examined the effect of the cytokines IL-1 alpha, IL-4, IL-6, TNF
      alpha and lymphotoxin on the production of ET-1 by cultured vascular endothelial
      cells. RESULTS: ET levels in endothelial cell conditioned media were measured by
      radioimmunoassay. IL-4 and lymphotoxin had no effect on ET release by endothelial
      cells, while IL-6, TNF-alpha and IL-1 alpha stimulated ET mRNA expression and ET
      release in a dose dependent fashion. IL-6 was the most potent stimulator and IL-1
      was the least effective. The addition of neutralizing antibodies to the cytokines
      inhibited the observed increase in ET release. CONCLUSIONS: These results suggest
      that cytokines may play a significant role in the control of vascular tone.
      Furthermore, cytokines may indirectly contribute to the development of
      proliferative vascular lesions by stimulating smooth muscle and interstitial cell
      proliferation through their effects on endothelin release by the vascular
      endothelium.

PMID- 9196869
TI  - Evaluation of ELISA to detect Chlamydia trachomatis antigen in urine samples from
      arthritis patients.
AB  - OBJECTIVE: To determine whether examination of urine samples using ELISA allows
      the detection of asymptomatic C. trachomatis infection in arthritis patients.
      METHODS: The in vitro sensitivity of IDEIA Chlamydia ELISA to detect C.
      trachomatis in urine samples was determined by the investigation of serial
      dilutions of chlamydial elementary bodies. In a clinical study, urine samples
      from 402 consecutive arthritis patients (182 men and 220 women) in a tertiary
      care rheumatology clinic were examined for asymptomatic chlamydial infection by
      ELISA and the results were compared to culture and direct immunofluorescence
      assay (DFA, MicroTrak) of urogenital swabs. RESULTS: The in vitro sensitivity of
      ELISA for detecting purified elementary bodies of C. trachomatis serovar K in
      urine was 60 infection forming units. Twenty-three of 402 arthritis patients (6%)
      had asymptomatic chlamydial infection as shown by DFA and culture from urogenital
      smears. The ELISA method identified only 3 of 17 swab-positive patients among 271
      patients when urine specimens were collected during the clinical visit, while the
      assay detected all 6 swab-positive patients among 131 patients when first-voided
      early morning urine specimens were used (p < 0.001). CONCLUSION: It is mandatory
      to examine only first voided early morning urine samples if ELISA is used instead
      of DFA or culture from urogenital swabs to detect asymptomatic chlamydial
      infection in arthritis patients.

PMID- 9196870
TI  - The impact of life events on patients with rheumatoid arthritis: a psychological
      myth?
AB  - OBJECTIVE AND METHODS: A large number of studies from the field of
      "psychorheumatology" have investigated the relationship between critical life
      events and disease parameters with varying results. In the present study 48
      patients with rheumatoid arthritis (RA) (mean age 57.8; range 32-78 years) were
      questioned about life events within the past two years using an "inventory for
      assessing life change events"-ILE (1). In contrast to previous studies, this
      inventory not only assesses the number of life events, but also captures the
      extent of subjectively experienced stress caused by these events. Since
      psychosocial factors such as social support and coping strategies influence
      subjectively experienced stress, these factors were taken into consideration for
      the definition of "life event". Furthermore, a series of objective medical
      parameters as well as the patient's and the physician's subjective impression of
      disease activity were assessed. RESULTS: The results show that patients with RA
      in the earlier stages of the disease cannot be differentiated from severely
      affected patients in later stages on the basis of life event parameters. In
      addition, no differences in the life event data could be observed between
      patients with and those without subjectively experienced episodes of illness in
      the two years immediately preceding the study. CONCLUSION: Our results suggest
      that the course of RA is influenced neither by the number of life events nor by
      the extent of stress caused by these life events. Therefore, the role of life
      events should not be overemphasized, at least as far as the disease parameters in
      RA is concerned.

PMID- 9196871
TI  - Features of SLE in various ethnic groups in Israel.
AB  - OBJECTIVE: To assess the association between the ethnic origin of patients with
      SLE living in Israel, and the clinical and laboratory features of SLE. METHODS: A
      retrospective review of medical records was carried out. Patients were classified
      into 3 groups based on their ethnic origin: a) Ashkenazi Jews, b) Sepharadic Jews
      and c) Arabs. RESULTS: The study included 74 consecutive SLE patients, 69 (93%)
      women and 5 (7%) men. Their mean age at diagnosis was 32 years and their mean
      disease duration was 6.4 years. There were 21 (28%) Ashkenazi Jews, 31 (42%)
      Sepharadic Jews and 22 (30%) Arabs. The demographics, the frequency of various
      clinical and laboratory variables of SLE, and the mean disease activity index
      score (SLEDA1) of the three groups were not statistically different. CONCLUSION:
      The ethnic origin of SLE patients living in Israel is not associated with the
      clinical and laboratory features of the disease.

PMID- 9196873
TI  - Association of DMA and DMB with RA in Japanese.
AB  - OBJECTIVE: The contribution of polymorphism of DMA and DMB alleles to the
      pathogenesis of Japanese RA was studied. The association of DM alleles with HLA
      DRB1*0405 and *0802, which were positively and negatively susceptible to Japanese
      RA, respectively, is also discussed. METHODS: DMA and DMB typing was carried out
      in 91 Japanese RA patients and in 77 normal subjects by the PCR-RFLP (restriction
      fragment length polymorphism) method. HLA-DRB1*04 and *08 genotyping were carried
      out by the PCR-SSCP (single-stranded DNA conformation polymorphism) method.
      RESULTS: Allele frequencies of DMB*0101 and DMB*0102 were slightly higher (52.2%
      and 27.0%) and the allele frequency of DMB*0103 was slightly lower (25.8%) in RA,
      but these differences were not significant. The increase of DMB*0102 was due to a
      negative association with HLA-DRB1*0802 [p < 0.05, pc = not significant (NS)].
      The decrease of DMB*0103 was due to a positive association with DRB1*0802 (p <
      0.005, pc < 0.05). The increase of DMB*0101 was possibly due to a weak
      association with HLA-DRB1*0405, (p = NS). Positivity of rheumatoid factor did not
      affect the prevalence of DMA and DMB alleles. CONCLUSION: Association analysis
      among DMA, DMB and DRB1 (*0405 and *0802) indicate that slight increases or
      decreases in DMB*0101, DMB*0102 and DMB*0103 are not primary indicators but
      reflect an increase in HLA-DRB1* 0405 and a decrease in HLA-DRB1*0802 in Japanese
      RA.

PMID- 9196872
TI  - Non-organ specific autoantibodies against cellular components in HIV-1 infected
      individuals.
AB  - OBJECTIVE: To detect the presence of autoantibodies against cellular components
      in HIV-1 infected individuals. METHODS: Serum samples from 87 patients with HIV-1
      infection and from 17 healthy HIV-seronegative controls were tested using
      sensitive and specific techniques (immunoblot, RNA precipitation), as well as
      counterimmunoelectrophoresis and indirect immunofluorescence. RESULTS: Four sera
      (4.6%) showed reactivity in immunoblot against various unidentified cytoplasmic
      autoantigens. The four positive sera were obtained from patients belonging in
      equal numbers to the non-AIDS and AIDS groups. CONCLUSION: It appears that the
      production of antibodies against cellular components rarely occurs during the
      clinical course of HIV infection.

PMID- 9196874
TI  - Pleurisy in primary Sjogren's syndrome: T cell receptor beta-chain variable
      region gene bias and local autoantibody production in the pleural effusion.
AB  - Pleurisy with or without effusion has not been considered to be associated with
      primary Sjogren's syndrome (SS), but rather to represent a manifestation of the
      underlying disorder, usually rheumatoid arthritis in secondary SS. We describe a
      patient with primary SS who presented with pleural effusions (PE) as an initial
      manifestation. Serological studies of paired serum and PE specimens demonstrated
      the occurrence of local immune reactions in the pleura, including the production
      of rheumatoid factor and anti-SS-A antibody, the formation of immune complexes,
      and activation of complement. In addition, the analysis of T cell receptor beta
      chain variable (V beta) regions in the PE revealed the overexpression of a number
      of V beta gene products, including V beta 2 and V beta 13 that have previously
      been shown to be over-represented in the salivary glands of patients with SS.
      Thus, our report not only calls for an awareness of pleurisy as an extraglandular
      manifestation of primary SS, but suggests that a common biased T cell response
      might play a critical role in the pathogenesis of the glandular as well as
      extraglandular manifestations.

PMID- 9196875
TI  - Management of immune thrombocytopenic purpura associated with the
      antiphospholipid antibody syndrome.
AB  - Our two patients had "primary" antiphospholipid antibody syndrome without
      underlying systemic lupus erythematosus or other systemic autoimmune process, as
      well as symptomatic immune thrombocytopenic purpura (ITP). The thrombocytopenia
      did not respond to prolonged courses of corticosteroids and/or immune globulin
      infusions, but was controlled following splenectomy. The presence of serum
      antibodies to platelet surface glycoproteins, typical of ITP, could be helpful in
      the confirmation of both of these disorders in the same patient, rather than
      secondary thrombocytopenia. Management of such cases is confounded by an
      increased risk for both bleeding and thrombosis, including fetal death. To reduce
      the risk of fetal loss and thrombosis, both patients were advised to take aspirin
      80 mg daily. The frequency and clinical significance of this association would
      suggest that patients with ITP should be tested for antiphospholipid antibodies,
      particularly before pregnancy or surgical procedures. Patients with coexistent
      antiphospholipid antibody syndrome would be at increased risk for thrombosis in
      the post-operative period following splenectomy and should be given prophylactic
      anticoagulation.

PMID- 9196876
TI  - Anti-CD4 monoclonal antibody (mAb) and anti-idiotypic mAb to anti-CD4 in the
      therapy of autoimmune diseases.
AB  - The present report critically reviews the rationale, experimental and clinical
      effectiveness and limits of anti-CD4 monoclonal antibody (mAb) therapy.
      References are also made to a novel approach involving active immunotherapy and
      an anti-idiotypic mAb bearing the internal image of human CD4 antigen.
      Preliminary observations concerning the effects of this treatment in one patient
      with rheumatoid arthritis and in one patient with systemic lupus erythematosus
      are reported.

PMID- 9196877
TI  - Levels of cytokine inhibitors: a possible marker of disease activity in childhood
      dermatomyositis and polymyositis.
AB  - The levels of cytokines and of their inhibitors were assessed by ELISA in serum
      samples from 3 children with dermatomyositis (DM) and polymyositis (PM) who were
      followed for several years. We observed normal levels of IL-6 and TNF alpha, but
      increased concentrations of IL-1Ra and TNF-sR75 at disease onset, which was
      followed by a decrease in the levels of IL-1Ra and TNF-sR75 in the patients with
      a favorable disease outcome. In contrast, in the one patient who relapsed no
      correlation with the levels of cytokines or of their inhibitors could be
      established. These results suggest that cytokine inhibitors such as IL-1Ra and
      TNF-sR may be useful additional parameters for monitoring the evolution of DM and
      PM.

PMID- 9196878
TI  - IgG autoantibodies to complement C1q in pediatric-onset systemic lupus
      erythematosus.
AB  - OBJECTIVE: Antibodies to C1q (aC1q) have been found in up to 50% of adult
      patients with systemic lupus erythematosus (SLE) and have been associated with
      proliferative glomerulonephritis. We investigated the prevalence and clinical
      significance of aC1q in pediatric SLE. METHODS: Antibodies to C1q, measured by an
      ELISA method, were evaluated in 29 patients with childhood-onset SLE, 26 females
      and 3 males, aged 7.5 to 19.6 years. RESULTS: Seventeen (59%) of the 29 patients
      were initially positive for aC1q. No correlation was found between either the
      presence or titer of aC1q and any of the clinical manifestations, including
      nephritis. However, a significant correlation was observed between aC1q levels
      and anti-double-stranded DNA antibodies and C3 values. Serial determinations of
      aC1q in 23 patients showed a progressive decline in the titers with few
      significant fluctuations. Antibodies to C1q were not a reliable predictor of
      increased SLE activity, since they increased or became detectable in only 50% of
      the pre-flare sera. CONCLUSION: Antibodies to C1q were frequently positive in our
      patients with pediatric SLE and were correlated with laboratory variables of
      disease activity. However, unlike in adults with SLE, a high correlation between
      aC1q and glomerulonephritis was not found in these pediatric patients.

PMID- 9196879
TI  - Medium-vessel PAN-type vasculitis associated with myelodysplastic syndrome and
      presenting as bilateral perinephric hematomas.

PMID- 9196880
TI  - Eosinophilia-myalgia syndrome: description of an unusual case.

PMID- 9196881
TI  - Elevated serum eosinophilic cationic protein (ECP) and expression of pemphigus
      like antibodies in a case of eosinophilic fasciitis.

PMID- 9196882
TI  - Oligoarthritis in a HLA-B27 positive patient with a variant form of hairy cell
      leukaemia.

PMID- 9196883
TI  - Bioelectrical impedance techniques in medicine. Part I: Bioimpedance measurement.
      First section: general concepts.
AB  - After a brief historical overview, the concept of electrical impedance is
      introduced as a principle of transduction calling attention to the possible
      mechanisms by which a physiological event may change impedance, i.e., by
      geometric, resistivity, and/or permittivity changes. Thereafter, since impedance
      measurements usually require the injection of current, its biological effects are
      discussed in order to establish the safety criteria. Finally, the elements found
      in an impedancimetric circuit and their respective nature are presented and
      described. The particular behavior of the biological impedance and the
      electrode/electrolyte interface appear immediately as strikingly important. The
      section ends with a bird's-eye view of the basic circuitry to measure impedance.
      Each subsection is closed by partial conclusions to underline the relevant
      concepts.

PMID- 9196884
TI  - Bioelectrical impedance techniques in medicine. Part I: Bioimpedance measurement.
      Second section: impedance spectrometry.
AB  - Electrical impedance spectrometry is an important application field of
      bioimpedance measurements. After introducing the electrical properties of
      biological tissues, this part presents instrumental aspects and applications of
      electrical impedance spectrometry. The main instrumental constraints encountered
      in spectrometric electrical impedance measurements are reviewed, focusing on low
      frequency applications. Examples of impedance cells and probes are presented and
      several instrumental setups operating in the frequency and time domain are
      described. Some examples of applications are presented, including in vitro
      characterization and modeling of normal tissues, in vitro and in vivo
      characterization of cancerous tissues, and assessment of tissue
      perfusion/ischemia levels.

PMID- 9196885
TI  - Bioelectrical impedance techniques in medicine. Part II: Monitoring of
      physiological events by impedance.
AB  - The measurement of a physiological event caused by a change in dimension,
      conductivity, or permittivity can be easily carried out by the impedance
      technique, requiring only the application of two or more electrodes, which are
      easy to apply. In some cases, the impedance is transformed into its resistive and
      reactive components, in others the total impedance is measured. In certain cases
      only a change in impedance, with or without separation into its components,
      contains enough information to be correlated to the physiological event. Recent
      measurements of physiological data by impedance techniques have reemphasized the
      value of the painless and harmless acquisition from human and animal subjects in
      such diverse domains as manned spacecraft, nutrition, and electrical impedance
      imaging. This part attempts to present all the numerous experiments performed on
      humans to estimate changes in volume, orientation, and distribution of fluids and
      tissues accompanying physiological activity. The main sections concern the
      respiratory system, the cardiovascular system, the brain, the total body
      impedance, muscle and skin impedance, and bacteriometry.

PMID- 9196886
TI  - Bioelectrical impedance techniques in medicine. Part III: Impedance imaging.
      First section: general concepts and hardware.
AB  - Measurement accuracy is a key point in impedance imaging and is mainly limited by
      factors that take place in the acquisition system. This part is a review of
      hardware solutions developed in acquisition systems for electrical impedance
      tomography (EIT). The general principles of EIT along with the changes that have
      taken place in the last decade, in terms of measurement strategy, and a certain
      number of definitions are introduced. The major hardware error sources that occur
      in the front end of EIT systems are presented. A review of the various
      alternatives published in the literature that are used to drive current,
      including current and voltage approaches, and the main solutions recommended in
      the literature to overcome the key point drawbacks of voltage measurement
      systems, including voltage buffers, instrumentation amplifiers, and demodulators,
      are provided. Some calibration procedures and approaches for the evaluation of
      the performance of EIT systems are also presented.

PMID- 9196887
TI  - Bioelectrical impedance techniques in medicine. Part III: Impedance imaging.
      Second section: reconstruction algorithms.
AB  - This section is devoted to the reconstruction algorithms published in the
      literature and developed for reconstructing the electrical conductivity and
      permittivity inside a body from measurements made on the body surface. These
      algorithms fall into two main categories. The first, based on linear
      approximations, are noniterative methods assuming that conductivity does not
      differ very much from a constant. Examples of noniterative methods are the Barber
      Brown back-projection method and related methods, the Calderon's approach, the
      moment method, and one-step Newton methods. The second class of methods consists
      of iterative methods, which typically include output least squares for various
      functions. A related class includes the adaptive methods, in which the applied
      patterns of current are adjusted to get the best signal. A review of all these
      different alternatives is presented.

PMID- 9196888
TI  - Bioelectrical impedance techniques in medicine. Part III: Impedance imaging.
      Third section: medical applications.
AB  - In several areas of clinical medicine, electrical impedance tomography could
      offer significant advantages over existing methods. These advantages have been
      supported by preliminary studies or by validation studies, which are described.
      The suggested applications are reviewed in this section. They mainly concern
      developments in impedance variations on brain, lung (neonatal, edema, emphysema),
      and heart; changes in blood volume, gastrointestinal system (gastric emptying,
      gastroesophageal reflux, pharyngeal transit time); pelvis (pelvis congestion);
      and thermal mapping in hyperthermia and breast (tissue characterization). The
      conductivity information at one frequency in a pixel is insufficient to take into
      account the very complex physiological mechanisms that underlie the observed
      impedance changes. To gain a better understanding of these mechanisms, research
      is currently being carried out on imaging of the imaginary part, parametric
      imaging, spectroscopic imaging, and 3D imaging, which are developed at the end of
      this section.

PMID- 9196889
TI  - Cytogenetic, morphologic and oncogene analysis of a cell line derived from a
      heterologous mixed mullerian tumor of the ovary.
AB  - A cell line was established from a mixed mullerian tumor of the ovary and
      designated LN1. Histopathologic analysis of the fresh tumor specimen demonstrated
      a highly aneuploid heterologous tumor comprised of undifferentiated mesodermal
      components with carcinomatous cells present as a smaller population. Long-term in
      vitro culture resulted in the establishment of a cell line that exhibits an
      epithelial-like morphology and expresses epithelial antigens cytokeratin,
      epithelial membrane antigen, and carcinoma antigen TAG-72. These cells also
      express mesenchymal intermediate filaments, vimentin, and desmin. Karyotypic
      analysis revealed a basic triploid pattern with multiple chromosomal
      abnormalities, most notably an isochromosome of the short arm of five present in
      three copies. Analysis of oncogene expression revealed that LN1 cells
      constitutively express mRNA for c-ras, c-erbB2, and p53. The expression of mRNA
      for cellular oncogenes correlated with the presence of corresponding
      oncoproteins, p21H-ras, p21K-ras, and p185erB2 and mutant p53 protein. In
      summary, coexpression of epithelial and mesenchymal antigens by LN1 cells lends
      support to the hypothesis that epithelial and mesenchymal elements comprising
      mixed mullerian tumors of the ovary are derived from a common stem cell
      precursor. Furthermore, this cell line represents a functional in vitro model to
      evaluate the biologic activities of these unusual and highly aggressive ovarian
      malignancies.

PMID- 9196890
TI  - Cultivation of fall armyworm ovary cells in simulated microgravity.
AB  - A methodology is presented to culture Fall Armyworm Ovary cells in simulated
      micrograviy using a novel bioreactor developed by NASA, the High-Aspect Ratio
      Vessel. In this vessel, the growth and metabolic profile for these insect cells
      were profoundly different than those obtained in shaker-flask culture.
      Specifically, stationary phase in the NASA vessel was extended from 24 h to at
      least 7 d while cell concentration and viability remained in excess of 1 x 10(7)
      viable cells/ml and 90%, respectively. Measurements of glucose utilization,
      lactate production, ammonia production, and pH change indicate that simulated
      microgravity had a twofold effect on cell metabolism. Fewer nutrients were
      consumed and fewer wastes were produced in stationary phase by as much as a
      factor of 4 over that achieved in shaker culture. Those nutrients that were
      consumed in the NASA vessel were directed along different metabolic pathways as
      evidenced by an extreme shift in glucose utilization from consumption to
      production in lag phase and a decrease in yield coefficients by one half in
      stationary phase. These changes reflect a reduction in hydrodynamic forces from
      over 1 dyne/cm2 in shaker culture to under 0.5 dyne/cm2 in the NASA vessel. These
      results suggest that cultivation of insect cells in simulated microgravity may
      reduce production costs of cell-derived biologicals by extending production time
      and reducing medium requirements.

PMID- 9196891
TI  - Neonatal rat heart cells cultured in simulated microgravity.
AB  - In vitro characteristics of cardiac cells cultured in simulated microgravity are
      reported. Tissue culture methods performed at unit gravity constrain cells to
      propagate, differentiate, and interact in a two-dimensional (2D) plane. Neonatal
      rat cardiac cells in 2D culture organize predominantly as bundles of
      cardiomyocytes with the intervening areas filled by nonmyocyte cell types. Such
      cardiac cell cultures respond predictably to the addition of exogenous compounds,
      and in many ways they represent an excellent in vitro model system. The gravity
      induced 2D organization of the cells, however, does not accurately reflect the
      distribution of cells in the intact tissue. We have begun characterizations of a
      three-dimensional (3D) culturing system designed to mimic microgravity. The NASA
      designed High-Aspect Ratio Vessel (HARV) bioreactors provide a low shear
      environment that allows cells to be cultured in static suspension. HARV-3D
      cultures were prepared on microcarrier beads and compared to control-2D cultures
      using a combination of microscopic and biochemical techniques. Both systems were
      uniformly inoculated and medium exchanged at standard intervals. Cells in control
      cultures adhered to the polystyrene surface of the tissue culture dishes and
      exhibited typical 2D organization. Cells cultured in HARVs adhered to
      microcarrier beads, the beads aggregated into defined clusters containing 8 to 15
      beads per cluster, and the clusters exhibited distinct 3D layers: myocytes and
      fibroblasts appeared attached to the surfaces of beads and were overlaid by an
      outer cell type. In addition, cultures prepared in HARVs using alternative
      support matrices also displayed morphological formations not seen in control
      cultures. Generally, the cells prepared in HARV and control cultures were
      similar; however, the dramatic alterations in 3D organization recommend the HARV
      as an ideal vessel for the generation of tissuelike organization of cardiac cells
      in vitro.

PMID- 9196892
TI  - GTSF-2: a new, versatile cell culture medium for diverse normal and transformed
      mammalian cells.
AB  - The aim of this study was to test the versatility of a new basal cell culture
      medium, GTSF-2. In addition to traditional growth-factors, GTSF-2 contains a
      blend of three sugars (glucose, galactose, and fructose) at their physiological
      levels. For these studies, we isolated normal endothelial cells from human,
      bovine, and rat large blood vessels and microvessels. In addition, GTSF-2 was
      also tested as a replacement for high-glucose-containing medium for PC12
      pheochromocytoma cells and for other, transformed cell lines. The cell growth
      characteristics were assessed with a novel cell viability and proliferation
      assay, which is based on the bioreduction of the fluorescent dye, Alamar Blue.
      After appropriate calibration, the Alamar Blue assay was found to be equivalent
      to established cell proliferation assays. Alamar Blue offers the advantage that
      cell proliferation can be measured in the same wells over an extended period of
      time. For some of the cell types (e.g., endothelial cells isolated from the
      bovine aorta, the rat adrenal medulla, or the transformed cells), proliferation
      in unmodified GTSF-2 was equivalent to that in the original culture media. For
      others cell types (e.g., human umbilical vein endothelial cells and PC12 cells),
      GTSF-2 proved to be a superior growth medium, when supplemented with simple
      additives, such as endothelial cell growth supplement (bFGF) or horse serum. Our
      results suggest that GTSF-2 is a versatile basal medium that will be useful for
      studying organ-specific differentiation in heterotypic coculture studies.

PMID- 9196893
TI  - Induction of carcinoembryonic antigen expression in a three-dimensional culture
      system.
AB  - MIP-101 is a poorly differentiated human colon carcinoma cell line established
      from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a
      180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA),
      a related protein that has 50 and 90 kDa isoforms, in monolayer culture. However,
      MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when
      implanted into subcutaneous tissue. We tested whether three-dimensional (3D)
      growth was a sufficient stimulus to produce CEA and NCA 50/90 in MIP-101 cells,
      because cells grow in 3D in vivo rather than in two-dimensions (2D) as occurs in
      monolayer cultures. To do this, MIP-101 cells were cultured on microcarrier beads
      in 3D cultures, either in static cultures as nonadherent aggregates or under
      dynamic conditions in a NASA-designed low shear stress bioreactor. MIP-101 cells
      proliferated well under all three conditions and increased CEA and NCA production
      three- to four-fold when grown in 3D cultures compared to MIP-101 cells growing
      logarithmically in monolayers. These results suggest that 3D growth in vitro
      simulates tumor function in vivo and that 3D growth by itself may enhance
      production of molecules that are associated with the metastatic process.

PMID- 9196894
TI  - Three-dimensional culture of bovine chondrocytes in rotating-wall vessels.
AB  - The Rotating-Wall Vessel (RWV) was used to culture chondrocytes for 36 d to
      observe the influence of low-shear and quiescent culture conditions allowing
      three-dimensional freedom on growth, differentiation, and extracellular matrix
      formation. Chondrocytes were freshly isolated from bovine cartilage and placed
      into the RWV with Cytodex-3 microcarriers. Nonadherent petri dishes were
      initiated with microcarriers as representative of standard culture conditions. In
      the RWV, large three-dimensional aggregates (5-7 mm) were formed in suspension.
      In addition, a large sheet of matrix adhered to the oxygenator core and vessel
      endcaps. Petri dish culture resulted in the formation of sheets of chondrocytes
      with no matrix production. Immunocytochemical analyses on histologic sections of
      tissue obtained from the RWV and the petri dish controls were performed with
      antibodies against fibronectin, collagen II, chondroitin-4-sulfate, chondroitin-6
      sulfate, and vimentin. Results demonstrated increased signal in the RWV material
      while the petri dishes demonstrated a slight decrease in signal. In addition,
      differentiated chondrocytes were observed in sections of RWV material through 36
      d, while few were observed in the sections of petri dish material. These results
      indicate that the unique conditions provided by the RWV afford access to cellular
      processes that signify the initiation of differentiation as well as production of
      normal matrix material.

PMID- 9196895
TI  - Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of
      in vivo characteristics.
AB  - The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to
      successfully culture a cell line derived from a heterologous mixed mullerian
      tumor cell of the ovary. Although the original tumor was comprised of both
      epithelial and mesodermal components, long-term culture in conventional flasks
      established a cell line from this tumor with homogeneous epitheliallike growth
      characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall
      Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of
      tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous
      cell populations organized into three-dimensional tissuelike architecture.
      Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated
      by expression of both epithelial and mesenchymal antigens. Reverse transcription
      polymerase chain reaction amplification demonstrated the presence of mRNA for
      cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there
      are two advantages to propagation of tissue in the RWV culture system:(a) tissue
      diversification representing populations present in the original tumor, and (b)
      the three-dimensional freedom to organize tissues morphologically akin to those
      observed in vivo. These data indicate that the RWV culture system is suitable for
      generating large quantities of ovarian tumor cells in vitro that are amenable to
      immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

PMID- 9196896
TI  - Establishment of a three-dimensional human prostate organoid coculture under
      microgravity-simulated conditions: evaluation of androgen-induced growth and PSA
      expression.
AB  - A novel in vitro human prostate cancer model was established by using a coculture
      technique in which isolated human prostate fibroblasts were observed to grow as a
      mixed culture with isolated human prostate cancer cells (LNCaP) on microcarrier
      beads under microgravity-simulated conditions. This model appears to be promising
      and deserves further exploration because: (a) cocultured human prostate
      fibroblasts and cancer epithelial cells appear to undergo patterns of
      histogenesis similar to those observed in human prostate tumors and (b) unlike
      the conventional cell culture on plastic dishes, cocultured human prostate
      fibroblasts and LNCaP cells in microgravity-simulated conditions responded to the
      inductive signals of growth and differentiation from dihydrotestosterone in a
      manner similar to that observed in the in vivo condition. These results offer an
      opportunity to examine molecular mechanisms of cellular signaling in response to
      androgen stimulation during normal and aberrant human prostate development. The
      microgravity-simulated three-dimensional prostate epithelial cell culture with
      prostate fibroblasts can be further explored as an ideal in vitro model for the
      study of normal and neoplastic prostate development. This model could also be
      adopted as a drug screening program for the discovery of novel therapeutic agents
      in the treatment of human prostate cancer and benign hyperplastic growth.

PMID- 9196898
TI  - Skeletal muscle satellite cells cultured in simulated microgravity.
AB  - Satellite cells are postnatal myoblasts responsible for providing additional
      nuclei to growing or regenerating muscle cells. Satellite cells retain the
      capacity to proliferate and differentiate in vitro and, therefore, provide a
      useful model to study postnatal muscle development. Most culture systems used to
      study postnatal muscle development are limited by the two-dimensional (2-D)
      confines of the culture dish. Limiting proliferation and differentiation of
      satellite cells in 2-D could potentially limit cell-cell contacts important for
      developing the level of organization in skeletal muscle obtained in vivo.
      Culturing satellite cells on microcarrier beads suspended in the High-Aspect
      Ratio-Vessel (HARV) designed by NASA provides a low shear, three-dimensional (3
      D) environment to study muscle development. Primary cultures established from
      anterior tibialis muscles of growing rats (approximately 200 gm) were used for
      all studies and were composed of greater than 75% satellite cells. Different
      inoculation densities did not affect the proliferative potential of satellite
      cells in the HARV. Plating efficiency, proliferation, and glucose utilization
      were compared between 2-D culture and 3-D HARV culture. Plating efficiency (cells
      attached divided by cells plated x 100) was similar between the two culture
      systems. Proliferation was reduced in HARV cultures and this reduction was
      apparent for both satellite cells and nonsatellite cells. Furthermore, reduction
      in proliferation within the HARV could not be attributed to reduced substrate
      availability because glucose levels in medium from HARV and 2-D cell culture were
      similar. Morphologically, microcarrier beads within the HARV were joined together
      by cells into 3-D aggregates composed of greater than 10 beads/aggregate.
      Aggregation of beads did not occur in the absence of cells. Myotubes were often
      seen on individual beads or spanning the surface of two beads. In summary,
      proliferation and differentiation of satellite cells on microcarrier beads within
      the HARV bioreactor results in a 3-D level of organization that could provide a
      more suitable model to study postnatal muscle development than is currently
      available with standard culture methods.

PMID- 9196897
TI  - Microgravity tissue engineering.
AB  - Tissue engineering studies were done using isolated cells, three-dimensional
      polymer scaffolds, and rotating bioreactors operated under conditions of
      simulated microgravity. In particular, vessel rotation speed was adjusted such
      that 10 mm diameter x 2 mm thick cell-polymer constructs were cultivated in a
      state of continuous free-fall. Feasibility was demonstrated for two different
      cell types: cartilage and heart. Conditions of simulated microgravity promoted
      the formation of cartilaginous constructs consisting of round cells, collagen and
      glycosaminoglycan (GAG), and cardiac tissue constructs consisting of elongated
      cells that contracted spontaneously and synchronously. Potential advantages of
      using a simulated microgravity environment for tissue engineering were
      demonstrated by comparing the compositions of cartilaginous constructs grown
      under four different in vitro culture conditions: simulated microgravity in
      rotating bioreactors, solid body rotation in rotating bioreactors, turbulent
      mixing in spinner flasks, and orbital mixing in petri dishes. Constructs grown in
      simulated microgravity contained the highest fractions of total regenerated
      tissue (as a percent of construct dry weight) and of GAG, the component required
      for cartilage to withstand compressive force.

PMID- 9196899
TI  - A novel culture morphology resulting from applied mechanical strain.
AB  - To demonstrate that cells both perceive and respond to external force, a
      strain/relaxation regimen was applied to normal human fetal and aged dermal
      fibroblasts cultured as monolayers on flexible membranes. The precisely
      controlled protocol of stretch (20% elongation of the culture membrane) at 6.67
      cycles/min caused a progressive change in the monolayers, such that the original
      randomly distributed pattern of cells became a symmetric, radial distribution as
      the cell bodies aligned parallel to the applied force. High cell density
      interfered with the success of re-alignment in the fetal cell cultures observed,
      which may reflect a preference in this cell strain for cell-cell over cell-matrix
      contacts. The chronologically aged cells observed did not demonstrate this
      feature, aligning efficiently at all seeding densities examined. The role of
      microfilaments in force perception and transmission was investigated through the
      addition of cytochalasin D in graded doses. Both intercellular interactions and
      cytoskeletal integrity mediate the morphological response to mechanical strain.

PMID- 9196901
TI  - Early onset autosomal dominant myopathy with rigidity of the spine: a possible
      role for laminin beta 1?
AB  - We describe 17 individuals from seven families with a slowly progressive, early
      onset, autosomal dominant myopathy with proximal muscle weakness, calf
      hypertrophy, contractures, spinal rigidity and, in five of the adult cases, a
      cardiac conduction defect. A deficiency of the laminin beta 1 chain of the
      skeletal muscle fibres was found in the older individuals of these families, but
      not the younger members. Other laminin chains, dystrophin and the dystrophin
      associated glycoproteins were normal. The age-related deficiency of the laminin
      beta 1 is restricted to the skeletal muscle fibres and not the vascular tissue,
      suggesting that this may be a secondary phenomenon. These findings suggest that a
      laminin or a laminin-binding protein is implicated in some forms of dominant limb
      girdle myopathies.

PMID- 9196900
TI  - Changes in gravity inhibit lymphocyte locomotion through type I collagen.
AB  - Immunity relies on the circulation of lymphocytes through many different tissues
      including blood vessels, lymphatic channels, and lymphoid organs. The ability of
      lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues
      can be determined in vitro by assaying their capacity to locomote through Type I
      collagen. In an attempt to characterize potential causes of microgravity-induced
      immunosuppression, we investigated the effects of simulated microgravity on human
      lymphocyte function in vitro using a specialized rotating-wall vessel culture
      system developed at the Johnson Space Center. This very low shear culture system
      randomizes gravitational vectors and provides an in vitro approximation of
      microgravity. In the randomized gravity of the rotating-wall vessel culture
      system, peripheral blood lymphocytes did not locomote through Type I collagen,
      whereas static cultures supported normal movement. Although cells remained viable
      during the entire culture period, peripheral blood lymphocytes transferred to
      unit gravity (static culture) after 6 h in the rotating-wall vessel culture
      system were slow to recover and locomote into collagen matrix. After 72 h in the
      rotating-wall vessel culture system and an additional 72 h in static culture,
      peripheral blood lymphocytes did not recover their ability to locomote. Loss of
      locomotory activity in rotating-wall vessel cultures appears to be related to
      changes in the activation state of the lymphocytes and the expression of adhesion
      molecules. Culture in the rotating-wall vessel system blunted the ability of
      peripheral blood lymphocytes to respond to polyclonal activation with
      phytohemagglutinin. Locomotory response remained intact when peripheral blood
      lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to
      introduction into the rotating-wall vessel culture system. Thus, in addition to
      the systemic stress factors that may affect immunity, isolated lymphocytes
      respond to gravitational changes by ceasing locomotion through model
      interstitium. These in vitro investigations suggest that microgravity induces non
      stress-related changes in cell function that may be critical to immunity.
      Preliminary analysis of locomotion in true microgravity revealed a substantial
      inhibition of cellular movement in Type I collagen. Thus, the rotating-wall
      vessel culture system provides a model for analyzing the microgravity-induced
      inhibition of lymphocyte locomotion and the investigation of the mechanisms
      related to lymphocyte movement.

PMID- 9196902
TI  - Proximal myotonic dystrophy--a family with autosomal dominant muscular dystrophy,
      cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic
      syndromes?
AB  - We describe a family with an autosomal dominant, multisystem disorder, consisting
      of late-onset proximal muscular dystrophy, electrophysiological myotonia,
      cataracts, late-onset deafness and male hypogonadism. Four patients were
      available for clinical examinations. Examination of asymptomatic family members
      revealed another patient with bilateral cataracts but without definite muscle
      disorder. Five deceased members of the family had proximal muscle weakness,
      reportedly or confirmed in medical records. Molecular examination of genomic DNA
      showed no expansion of the unstable (CTG)n trinucleotide repeat on chromosome
      19q13.3 associated with myotonic dystrophy (DM). Linkage to two loci implicated
      in other myotonic disorders, the muscle chloride channel (CLCN1) gene, and the
      muscle sodium channel (SCN4A) gene, was assessed and excluded. The clinical
      findings differ from those described in proximal myotonic myopathy (PROMM), in
      terms of the more severe muscle involvement with atrophy of affected muscles and
      the hearing loss. These findings suggest phenotypic and probably genetic
      heterogeneity among the proximal myotonic syndromes.

PMID- 9196903
TI  - A European family with histidine 58 transthyretin mutation in familial amyloid
      polyneuropathy.

PMID- 9196905
TI  - Hypokalemic periodic paralysis: an autosomal dominant muscle disorder caused by
      mutations in a voltage-gated calcium channel.
AB  - Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder
      characterized by acute attacks of muscle weakness concomitant to a drop in blood
      potassium levels. Recent molecular work has shown that hypoPP is due to mutations
      in a skeletal muscle voltage-gated calcium channel: the dihydropyridine receptor
      (DHP receptor). Mutations affect segments S4 of domains II and IV, changing an
      arginine in position 528 and 1239 into an histidine, or an histidine or a glycine
      respectively. Surprisingly, expressing in vitro mutants channels in a non
      muscular environment resulted in functional calcium channels with minor
      modifications in electrophysiological properties. Expressing mutant channels in a
      muscular environment or transgenic mice might help to bridge the gap between the
      knowledge of the molecular defect and the understanding of the pathophysiology of
      the disease.

PMID- 9196904
TI  - C4342T-mutation in the SCN4A gene on chromosome 17q in a Swedish family with
      paramyotonia congenita (Eulenburg)--correlations with clinical,
      neurophysiological and muscle biopsy data.
AB  - Genetic analysis of the adult muscle sodium channel alpha-subunit, SCN4A gene on
      chromosome 17q, was performed by means of PCR technique in a Swedish family with
      paramyotonia congenita (Eulenburg) (PMC). The mutation was found in four family
      members and consisted of a C to T transition affecting the fourth domain of the
      sodium channel protein. This mutation has earlier been described in other
      families with paramyotonia congenita. All family members carrying the mutation
      had cold-induced paradoxical myotonia, myotonic bursts on EMG, and a type IIB
      atrophy on muscle biopsy. Three of them had slight CK elevation and two had
      episodes of paralysis. On the basis of clinical findings in this family,
      persistent proximal muscle weakness, myopathic EMG abnormalities, a type IIB
      atrophy on muscle biopsy and no symptoms but other signs of muscle affection,
      were earlier suggested as clinical features of PMC. However, genetic analysis
      revealed that family members with these symptoms and findings did not have the
      mutation, indicating that these features are not due to PMC.

PMID- 9196906
TI  - From mutation to myotonia in sodium channel disorders.
AB  - Hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium
      aggravated myotonias are all caused by point mutations in the alpha-subunit of a
      sodium channel expressed selectively in skeletal muscle. This review updates the
      growing list of genotype-phenotype correlations for these mutations and
      summarizes the alterations in channel function they produce. A toxin-based in
      vitro model demonstrates that subtle defects in sodium channel inactivation are
      sufficient to cause myotonia and computer modeling suggests that specific types
      of inactivation defect may predispose to paralysis or myotonia.

PMID- 9196907
TI  - Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal
      disorders of the nervous system.
AB  - Some of the most common diseases in humans occur intermittently in people who are
      otherwise healthy and active. Such disorders include migraine headache, epilepsy,
      and cardiac arrhythmias. Because electrical signals are critical to the function
      of neurons, muscle cells, and heart cells, proteins that regulate electrical
      signaling in these cells are logical sites where abnormalities might lead to
      disease. All of these diseases have prominent genetic components. Difficulty in
      understanding these diseases arises from the complexity of the clinical
      phenotypes as well as from the genetic heterogeneity that is almost certain to
      exist. Therefore, early work in may laboratory was aimed at understanding the
      pathogenesis of rare disorders that are similar in their episodic nature. These
      disorders of muscle (the periodic paralyses), lead to attacks of weakness that
      occur intermittently in otherwise normal people. We, and others, have shown that
      hyperkalemic periodic paralysis (hyperKPP) and paramyotonia congenita (PC) result
      from mutations in a gene encoding a skeletal muscle sodium channel. We have also
      shown that hypokalemic periodic paralysis (hypoKPP) is caused by mutations in a
      gene encoding a voltage-gated calcium channel. The characterization of these
      diseases as channelopathies has served as a paradigm for other episodic
      disorders. One example is periodic ataxia, which results from mutations in
      voltage-gated potassium calcium channels. Long QT syndrome, an episodic cardiac
      dysrhythmia syndrome, is known to result from mutations in either voltage-gated
      sodium or potassium channels. We have recently mapped genes that cause a familial
      paroxysmal dyskinesia (non-kinesiogenic paroxysmal dystonia/choreoathetosis) in
      humans and a reflex epilepsy in mice. The similarities among all these disorders,
      including their episodic nature, precipitating factors, and therapeutic
      responses, are striking. Understanding gained from work in these rare monogenic
      episodic disorders is not only allowing characterization of the molecular and
      physiologic basis of these diseases, but may ultimately shed light on our
      understanding of the pathophysiology of more common and genetically complex
      disorders of the central nervous system.

PMID- 9196908
TI  - Welander distal myopathy is not linked to other defined distal myopathy gene
      loci.
AB  - Welander distal myopathy is an autosomal dominant disorder with late onset that
      affects extensor muscles of the hands and the feet. The disorder is considered as
      the most prevalent of the distal myopathies and is almost only seen in Sweden and
      in some parts of Finland. On clinical, morphological and genetical grounds the
      disorder is clearly separated from other distal myopathies. We have performed
      linkage analysis with the MLINK program in a total of six families with
      microsatellite markers dispersed throughout the genome and report exclusion for
      the localisation of the gene of 64% of the human genome. These studies have
      clearly separated Welander distal myopathy from previously mapped forms of distal
      myopathy such as the Miyoshi myopathy by excluding linkage to chromosome 2. The
      region on 14q that has been suggested to house the gene of the distal myopathy
      described by Laing et al. (Am J Hum Genet 1995;56:422-7), has as well been
      excluded by several markers.

PMID- 9196909
TI  - 47th ENMC International Workshop: Treatment of Muscular Dystrophy. 13-15 December
      1996, Naarden, The Netherlands.

PMID- 9196910
TI  - 45th ENMC Workshop: Myotubular Myopathy. 13-15th September 1996, Naarden, The
      Netherlands.

PMID- 9196911
TI  - Mae III polymorphism in the NADH dehydrogenase subunit 4 gene.

PMID- 9196912
TI  - Neuromuscular disorders: gene location.

PMID- 9196913
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 9196914
TI  - A quarter century of violence in the United States. An epidemiologic assessment.
AB  - During the past quarter century violence consistently has been a major problem in
      the United States. During this period, the profile of violence has changed.
      Adolescent and young adults are assuming a substantially greater role in serious
      and fatal violent events. The increased use of firearms, particularly by male
      youth and young adults, has rendered their acts of violence more lethal.

PMID- 9196915
TI  - The developmental course of violence and aggression. Mechanisms of family and
      peer influence.
AB  - This article presents an overview of current research and thinking on the
      developmental course of aggression and violent behavior from early childhood
      through adolescence. Differing developmental trajectories are highlighted, and
      salient family and peer influences are described. Acquired social information
      processing patterns are discussed as potential mediators of the link between
      social experience in the family and peer group and individual differences in
      children's aggressive behavior. The need for developmentally sensitive models
      that focus on the interplay of family and peer experience, information processing
      patterns, and onset and chronicity of aggression is stressed.

PMID- 9196916
TI  - Genetics of aggressive and violent behavior.
AB  - This article develops the topic of the genetics of aggressive and violent
      behavior from three directions. Firstly, evidence from twin, family, and adoption
      studies will establish the case for the importance of genetically transmitted
      factors in the genesis of aggressivity from childhood through adulthood.
      Secondly, evidence from adoption studies will be presented to show that some
      environmental conditions interact with genetic factors in such a way as to
      suggest that the development of aggressivity requires that both genetic and
      environmental factors be present. Thirdly, additional and direct evidence of
      genetic factors in aggressivity is presented from the perspective of molecular
      genetics, where underlying biochemical mechanisms associated with aggressivity
      have been found to be caused by specific genes in animal models with confirmation
      of similar physiologic mechanisms in humans.

PMID- 9196917
TI  - Sociodemographic predictors of violence.
AB  - A representative sample of 25 years of research relating sociodemographic
      variables to violence is reviewed. Generalizations from those studies are applied
      to the authors' more recent research on domestic violence. Factors limiting the
      ability of the studies to be synthesized into a more meaningful whole are
      identified. Strategies to enhance the value of future studies are discussed.

PMID- 9196918
TI  - Psychological aspects of perpetrators of domestic violence and their
      relationships with the victims.
AB  - Domestic violence is a serious public health concern in the United States.
      Despite the serious and often tragically fatal consequences of spousal abuse, we
      have very little understanding about the root causes of domestic violence. We
      know even less about providing effective treatments and prevention. In this
      article, we have discussed some of the more promising individual difference
      variables that discriminate between violent and nonviolent men. We also have
      addressed some of the growing research on how violent couples are different from
      nonviolent ones. Unfortunately, methodologic limitations hamper us from being
      able to discuss definitive risk factors or predictive variables, but we can speak
      of factors associated with domestic violence. We also have discussed the
      importance of attending to important differences among violent men and violent
      couples. The complexity of battering behavior and battering relationships
      necessarily points researchers and clinicians toward multifaceted research
      designs and treatment models. The tragedy of domestic violence demands that
      science continues to address these crucial unanswered questions.

PMID- 9196919
TI  - Mental and physical health effects of intimate partner violence on women and
      children.
AB  - The battering of female partners and the concomitant emotional abuse that is
      almost always part of the coercive control have significant mental and physical
      health consequences for the women who experience this type of violence. Children
      who live in households fraught with the conflict, violence, and unpredictable
      danger of domestic violence often witness the battering of their mothers and may
      also be victims of child abuse themselves. This article highlights current
      knowledge regarding the mental and physical health effects of intimate partner
      violence on women and their children, and discusses needed directions for
      screening, intervention, research, and changes in the health care system.

PMID- 9196920
TI  - Psychophysiology of anger and violent behavior.
AB  - Antisocial behavior is a complex phenomenon that arises out of multiple causes
      involving biologic, psychological, and social forces. Moreover, different forms
      of violent antisocial behavior may each result from different biopsychosocial
      pathways. The overview of human psychophysiologic findings presented in this
      article provides some support for this notion. In particular, the finding of
      psychophysiologic underarousal (e.g., reduced resting HR and SC levels, increased
      slow-wave EEG, poor classical conditioning) is one of the most robust and best
      replicated findings in antisocial populations. The majority of these studies
      consist of populations exhibiting nonviolent antisocial behavior or milder forms
      of aggression. Findings of underarousal in institutionalized criminal samples are
      very few in number and are not well-replicated. The relationship of
      psychophysiologic underarousal to antisocial behavior, therefore, may be specific
      to covert forms of antisocial behavior and perhaps to some less severe forms of
      violent behavior. On the other hand, violence associated with anger and emotional
      aggression (which is often more impulsive, less controlled, and reactive to some
      perceived provocation) may have very different psychophysiologic underpinnings.
      It was suggested that risk factors for emotional aggression include a
      predisposition to negative affect/arousal and an inability to regulate that
      affect/arousal. It also was suggested that this effect will be most pronounced in
      individuals experiencing stressors or adverse social environments, where negative
      affect and arousal would be increased. Laboratory studies have suggested that
      overarousal may facilitate aggression in situations in which someone has been
      provoked. Clinical studies also have indicated a relationship between increased
      physiologic arousal, negative emotionality, and aggression/antisocial behavior in
      some populations, with increases in aggression in those also exposed to adverse
      home environments. Thus, the relationship of increased psychophysiologic arousal
      to antisocial behavior may be more specific to angry or emotional violence. It is
      important to note that these psychophysiologic distinctions are speculative for
      few studies actually have differentiated type of violence in their design. Pitts
      did group children according to proactive or reactive aggression and found
      reduced HR levels in both groups, but a substantial increase in HR only in the
      reactive aggressive group. Lakosina and Trunova found increased SC responsivity
      in psychopathic individuals characterized by affective violence. These studies
      provide some initial support for underarousal in proactive/instrumental
      aggression and overarousal in emotional aggression. It is important, however,
      that more studies be done with subtypes of violence to test the notion of such
      differential psychophysiologic patterns. Lastly, some definitional and
      methodologic considerations need to be mentioned. First, a distinction exists
      between physiologic arousal and reactivity. Typically, arousal refers to
      psychophysiologic activity that occurs during a resting state, whereas reactivity
      refers to activity that occurs in response to some stimulus. Although some
      studies did assess measures during a resting state, the majority of findings on
      over-arousal in relation to emotional aggression more accurately reflect
      psychophysiologic and emotional reactivity to a situation or stimulus. Second,
      arousal or reactivity are nonspecific terms that can refer to any
      psychophysiologic response system (e.g., electrodermal, cardiovascular, cortical,
      and so on). Responses from these systems typically do not correlate in the
      general population. Thus, it would be worthwhile for future studies to include
      more than one response system (as done by Raine et al) and see if the
      arousal/reactivity measures converge. If the measures converge, a general model
      of arousal or reactivity is supported. (ABSTRACT TRUNCATED)

PMID- 9196921
TI  - The neurobiology of impulsive aggression.
AB  - As noted previously, it is likely that the tendency to lash out verbally or
      physically at others is influenced by an interaction among multiple complex
      biologic factors. We need to investigate how these systems interact with each
      other to develop a more thorough understanding of the brain's influence over
      aggressive behavior. We are at a very early stage in our understanding of the
      neurobiology of aggression. There are no simple tools for studying the complex
      neurophysiology of the human brain. The studies cited in this article include
      techniques limited in their utility. As our technologies improve, discovering a
      more thorough picture of the brain's influence over aggressive behavior may be
      possible. For example, functional neuroimaging may help to localize abnormal
      neurotransmitter functioning in the brains of individuals with impulsive
      aggressive behavior. Our technologies are beginning to reveal the differential
      effects of subsystems of neurotransmitter regulation. Subtypes of serotonin
      receptors may differentially mediate impulsive aggressive behaviors. Animal
      studies suggest that 5-HT 1A receptor stimulation results in a decrease in
      aggressive behavior. As noted previously, aggressive personality-disordered
      patients show a blunted prolactin response to the 5-HT1A agonist buspirone.
      Antagonism of 5-HT 2 receptors appears to decrease aggression, and this effect
      may explain the ability of newer antipsychotic agents (which, unlike older
      antipsychotic medications, block 5-HT 2 receptors) to produce a dramatic
      reduction in aggression and agitation independent of effects on psychotic
      symptoms. Neglecting psychosocial factors in the causes of aggressive behavior
      would also be naive. Although environmental factors account for much of the
      predisposition to aggression, there have been few systematic studies to explore
      the relationship between life experiences and aggression. In addition, there have
      been no well-designed studies of the interaction between biology and an
      individual's environment in the genesis of aggressive behavior. There is some
      evidence of an association between childhood abuse and neglect and adult
      antisocial personality disorder, but this relationship might be merely an
      artifact of the genetic relationship between parental and offspring antisocial
      personality disorder. As we discussed in the introduction, one of the biggest
      hurdles in the study of the neurobiology of aggression is the lack of a consensus
      on definitions. "Intermittent Explosive Disorder" is the only category in DSM-IV
      that directly addresses individuals with problems with aggression, but the
      criteria are vague and only focus on a handful of the many patients who exhibit
      problems with aggressive behavior. It is our hope that investigators in this
      field can work together toward developing more precise and encompassing
      diagnostic criteria to study effectively both the neurobiology and treatment of
      these disorders.

PMID- 9196922
TI  - Violence and homicidal behaviors in psychiatric disorders.
AB  - Our review evaluating the relationship between violent/homicidal behaviors and
      mental illness/psychiatric disorders used many different data including that
      assessing the prevalence of violent/homicidal behaviors in former psychiatric
      inpatients (just before hospitalization, during hospitalization, and after
      discharge) as outpatients and in community samples as well as evaluating the
      prevalence rate of psychiatric disorders in people who actually engaged in
      violent/homicidal disorders (jail detainees, prison inmates, and community
      samples). Irrespective of which line of investigation, there was convincing
      evidence that violent/ homicidal behavior was associated significantly with
      mental illness. Although earlier investigations failed to control for important
      variables, such as age and sociodemographics, most studies reviewed in this
      article did control for these items, further underlining the association of
      violence and mental illness. The question of whether specific psychiatric
      diagnostic categories are associated with violent/homicidal behavior is less
      definite across the various studies reviewed. The presence of substance abuse and
      dependence and alcohol abuse and dependence as well as antisocial personality
      disorder are particularly associated with an increased risk of violent/homicidal
      behaviors. The risk for these latter behaviors in schizophrenia, mood disorders,
      and anxiety disorders may appear somewhat greater than that for a general
      population but are not of the same magnitude of that for substance abuse or
      antisocial personality disorder. Interestingly, our outpatient study found that
      homicidal behaviors were not associated with any specific psychiatric diagnosis.
      Although understanding whether specific psychiatric diagnostic categories are
      more prone to violent behaviors may be of importance, most studies have been
      shortsighted regarding this evaluation. All the studies presented in this article
      except the ECA project, presented diagnostic data where either the presence of
      one psychiatric disorder did not preclude the diagnosis of another or assigned
      subjects/patients into the severest disorder of a predetermined hierarchy of
      diagnoses or only selected their principal/primary diagnosis. Thus, the effect of
      having a solitary psychiatric disorder (only one disorder present) as well as the
      effect of comorbidity per se on the relationship of psychiatric disorders and
      violent/homicidal behaviors were unexplored. Only the ECA study by Swanson and
      colleagues reported on the effect of comorbidity. As reviewed earlier in the
      article, Swanson et al found that comorbidity of psychiatric diagnostic
      categories further increased the risk of violent/ homicidal behaviors. In most
      cases, it was many more times than simply adding the rates of either diagnosis
      alone. Because more than 54% of respondents of the National Comorbidity Survey
      study who had one DSM-III-R diagnosis also had at least a second Axis I
      diagnosis, the association of violent/homicidal behaviors to mental illness may
      even be stronger than originally believed. Within the relationship of
      violent/homicidal behaviors and mental illness, this article suggests a number of
      particular risk factors. As just reviewed, substance/alcohol abuse and antisocial
      personality disorder as well as the presence of comorbid psychiatric disorders
      are significant risk factors. Which particular comorbid illness increases the
      risk still needs further elaboration. Studies must continue to try to define and
      understand the relationship of violent/homicidal behaviors in mental illness.
      Although mental disorders per se are significantly associated with
      violent/homicidal behaviors, it is reasonable to believe that targeting certain
      subgroups of patients should be helpful. Probably the presence of psychotic
      symptoms is a significant risk factor in violent/ homicidal behaviors in the
      mentally ill. Only one of the studies reviewed in this article evaluated this
      issue. (ABSTRACT TRUNCATED)

PMID- 9196923
TI  - Psychopharmacologic treatment of pathologic aggression.
AB  - Several drugs are apparently effective in treating pathologic anger and
      aggression. Because many of the studies on aggressive populations allowed the use
      of concomitant medications, it is unclear whether the efficacy of each drug in a
      particular population is dependent on the presence of other medications, such as
      antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy
      of a particular drug in aggressive patients with neuropsychiatric conditions
      other than the ones in which some efficacy has been established. Lithium appears
      to be an effective treatment of aggression among nonepileptic prison inmates,
      mentally retarded and handicapped patients, and among conduct-disordered children
      with explosive behavior. Certainly, lithium would be the treatment of choice in
      bipolar patients with excessive irritability and anger outbursts, and it has been
      shown to be effective in this population. Anticonvulsant medications are the
      treatment of choice for patients with outbursts of rage and abnormal EEG
      findings. The efficacy of these drugs in patients without a seizure disorder,
      however, remains to be established, with the exception perhaps of valproate and
      carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in
      treating aggressive behavior in children with temper tantrums and was found to be
      effective in only a prison population. There is some evidence for the efficacy of
      carbamazepine and valproate in treating pathologic aggression in patients with
      dementia, organic brain syndrome, psychosis, and personality disorders. As
      Yudofsky et al point out in their review of the literature, although traditional
      antipsychotic drugs have been used widely to treat aggression, there is little
      evidence for their effectiveness in treating aggression beyond their sedative
      effect in agitated patients or their antiaggressive effect among patients whose
      aggression is related to active psychosis. Antipsychotic agents appear to be
      effective in treating psychotic aggressive patients, conduct-disordered children,
      and mentally retarded patients, with only modest effects in the management of
      pathologic aggression in patients with dementia. Furthermore, at least in one
      study, these drugs were found to be associated with increased aggressiveness in
      mentally retarded subjects. On the other hand, atypical antipsychotic agents
      (i.e., clozapine, risperidone, and olanzapine) may be more effective than
      traditional antipsychotic drugs in aggressive and violent populations, as they
      have shown efficacy in patients with dementia, brain injury, mental retardation,
      and personality disorders. Similarly, benzodiazepines can reduce agitation and
      irritability in elderly and demented populations, but they also can induce
      behavioral disinhibition. Therefore, one should be careful in using this class of
      drugs in patients with pathologic aggression. Beta-blockers appear to be
      effective in many different neuropsychiatric conditions. These drugs seem
      effective in reducing violent and assaultive behavior in patients with dementia,
      brain injury, schizophrenia, mental retardation, and organic brain syndrome. As
      pointed out by Campbell et al in their review of the literature, however,
      systematic research is lacking, and little is known about the efficacy and safety
      of beta-blockers in children and adolescents with pathologic aggression. Although
      widely used in the management of pathologic aggression, the use of this class of
      drugs has been limited partially by marked hypotension and bradycardia, which are
      side effects common at the higher doses. The usefulness of the antihypertensive
      drug clonidine in the treatment of pathologic aggression has not been assessed
      adequately, and only marginal benefits were observed with this drug in irritable
      autistic and conduct disorder children. Psychostimulants seem to be effective in
      reducing aggressiveness in brain-injured patients as well as in violent
      adolescents with oppositional or conduct disorders, particu

PMID- 9196924
TI  - Psychotherapeutic approaches to aggressive and violent patients.
AB  - Behavioral and cognitive-behavioral strategies and a broad range of group,
      family, couples, and milieu treatment approaches have been developed for the
      psychotherapy of aggressive and violent patients. These methods have been carried
      out in diverse settings ranging from hospitals and prisons to individual
      outpatient practices and have been applied across diverse populations including
      adults with mental retardation, dementia, and brain injury; children with
      attention deficit and conduct disorders and autism; recurrent violent offenders
      with antisocial personality disorder; and individuals with chronic psychotic
      disorders, mood disorders, or medical illnesses such as hypertension. Bridging
      these different strategies are the underlying principles of psychotherapy with
      aggressive and violent patients. These include ensuring the safety of clinician,
      patient, and potential victims as the foremost concern; developing a finely
      detailed assessment of aggressive and violent acts and of the antecedents,
      assumptions, and consequences that are attached to them; formulating well-defined
      goals and striving for clear communication to achieve consistency in the pursuit
      of these goals between therapist and patient, and among therapist and other
      clinicians, staff, and relevant family members or agencies; specifying ahead of
      time well-considered outcome measures to be used to gauge the effectiveness of
      treatment; and maintaining a healthy vigilance for countertransferential and
      similar reactions and a willingness to use consultation as an integral part of
      treatment.

PMID- 9196925
TI  - Legal issues in treating perpetrators and victims of violence.
AB  - Psychiatrists are faced increasingly with the difficult responsibility of
      evaluating perpetrators and victims of violence. The following guidelines will
      help the clinician avoid legal difficulty: 1. Become knowledgeable about your
      state statutes regarding civil commitment and duty to third parties. 2. Document
      thoroughly your risk assessment and the factors you considered in reaching your
      judgment. 3. Consider obtaining a second opinion in difficult cases. 4. Follow
      hospital policies regarding seclusion, restraints, and emergency medication of
      the patient. 5. Adhere to mandatory reporting requirements for victims of abuse.

PMID- 9196926
TI  - Macular hole surgery without face-down positioning. A pilot study.
AB  - PURPOSE: To investigate whether postoperative face-down positioning is necessary
      for successful macular hole repair. BACKGROUND: Although never proven, face-down
      positioning is strongly considered an important maneuver to achieve macular hole
      closure. Face-down posturing is inconvenient, and for patients with physical or
      mental limitations, weeks of face-down positioning may be an impossible task. A
      gas bubble that completely fills the vitreous cavity will tamponade a macular
      hole despite head position and may close a macular hole as effectively as a
      partial gas fill with face-down positioning. If face-down positioning were not
      necessary, more patients would be eligible to benefit from this surgery. METHODS:
      Thirty-three consecutive eyes in 31 patients aged 65-79 years with Stage II, III,
      or IV full-thickness macular holes underwent macular hole surgery with a complete
      15% C3F8 vitreous fill. Hole duration varied from 1 month to 10 years; in 21% of
      eyes, (seven of 33) holes had been present for more than 1 year. All phakic eyes
      (n = 25) had cataract extraction with intraocular lens insertion when macular
      hole surgery was done. No patients were positioned face down. RESULTS: The follow
      up period was 6-40 months; 73% of the patients have been observed for more than 1
      year. Preoperative hole duration did not affect hole closure rate. The success
      rate after one surgery was 79% (26 of 33 eyes), and with additional vitrectomy
      surgery, the total success rate was 85% (28 of 33 eyes). Forty-eight percent of
      eyes attained visual acuity of 20/50. Eighty percent of eyes with preoperative
      acuity of > 20/100 attained > 20/50 acuity. Significant complications included
      iris incarceration into the cataract wound during a postoperative fluid-gas
      exchange (one eye), posterior synechiae (four eyes), intraocular lens capture
      (two eyes), elevated intraocular pressure (three eyes), and retinal detachment
      (three eyes). Most of these problems can be avoided or reduced. CONCLUSION: This
      pilot study suggests that successful macular hole closure is possible without
      face-down positioning. This technique may be an alternative for patients with
      macular holes in pseudophakic eyes who are unable to assume face-down posturing.
      Combining cataract surgery with this technique for macular hole repair is
      reasonable for phakic patients who cannot maintain prone positioning. Major
      disadvantages of combined surgery include the morbidity of the second procedure
      and removal of a visually insignificant cataract. This approach should be
      considered for those patients unable to tolerate face-down positioning.

PMID- 9196927
TI  - The use of panoramic viewing system in relaxing retinotomy and retinectomy.
AB  - BACKGROUND: Retinotomies and retinectomies are surgical procedures mainly devoted
      to the peripheral retina that require optimal visibility and adequate
      magnification to make the surgeon's task easy, quick, and safe. The purpose of
      present study was to estimate to what extent the introduction of wide-angle
      viewing systems can help the surgeon perform safer and more effective retinotomy
      procedures. MATERIALS AND METHODS: The authors retrospectively analyzed the
      records of patients undergoing retinotomy procedures between 1993 and 1995 and
      divided them into two groups according to the viewing system used during the
      retinotomy procedures. Group 1 included 86 eyes that underwent surgery between
      July 1991 and June 1993 with Lander's plano-concave and prismatic lenses
      (Optikon, Rome, Italy), and group 2 included 96 eyes that underwent surgery
      between July 1993 and June 1995 with the Advanced Vitreoretinal Instruments
      system (New York, NY). Outcome measures were divided into preoperative (diagnosis
      at baseline, anterior proliferative vitreoretinopathy grade and extension, and
      visual acuity), intraoperative (size of retinotomy, number of laser spots, need
      for scleral depression, lensectomy, intraocular lens and capsule removal, and
      duration of treatment) and postoperative (anatomic success rates, visual acuity,
      postoperative intraocular pressure, and need for postoperative laser treatment
      and follow-up treatment). RESULTS: Among preoperative parameters, there were no
      significant differences between the two groups. For intraoperative parameters,
      eyes in group 2 underwent significantly shorter surgical procedures, had less of
      a need for scleral depression, and, as a group, had a higher average number of
      laser spots. For postoperative parameters, eyes in group 2 had a significantly
      lower need for laser treatment at the edge of retinotomy after surgery.
      CONCLUSION: Our results suggest that the use of a panoramic viewing system
      significantly decreases the time required for intervention, allowing more
      complete laser treatment along the edge of the retinotomy and lowering the need
      for scleral depression. The need for completion of laser treatment along the edge
      of the retinotomy after surgery also is reduced significantly, possibly
      increasing patient comfort because, especially in the early postoperative days,
      postoperative laser treatment can be extremely uncomfortable for the patient and
      difficult to perform for the surgeon. No prognostic benefit has been proven for
      any of the two groups because anatomic and visual results were overlapped.

PMID- 9196928
TI  - Branch retinal vein occlusion. Axial length and other risk factors.
AB  - OBJECTIVE: To determine the association between axial length, as a measurement of
      hyperopia, and branch retinal vein occlusion and to determine the clinical
      characteristics and other risk factors of patients with branch retinal vein
      occlusion. METHODS: A case-control study was performed using 36 patients with
      branch retinal vein occlusion and 36 age- and sex-matched control patients
      selected from a list of subjects who had undergone cataract extraction. RESULTS:
      There was essentially no difference in axial length between patients the disorder
      and control patients (23.55 mm versus 23.62 mm; P = 0.79). Although the
      intraocular pressure (IOP) among control eyes was somewhat higher than that in
      branch retinal vein occlusion eyes, the difference was not statistically
      significant (P = 0.32). Systemic hypertension was more common in patients with
      branch retinal vein occlusion (53%) than in control patients (42%) but the
      difference was not statistically significant (P = 0.35). Chronic open-angle
      glaucoma was present in 14% of patients with branch retinal vein occlusion and
      22% of control patients (P = 0.37), but this difference was not statistically
      significant. Diabetes mellitus was two times more common in controls (28%) than
      in patients with branch retinal vein occlusion (14%). This difference, however,
      also did not reach statistical significance (P = 0.13). CONCLUSIONS: Hyperopia as
      measured by axial length is not a risk factor for branch retinal vein occlusion.
      This study provides evidence that hypertension is a risk factor for branch
      retinal vein occlusion and that chronic open-angle glaucoma and diabetes mellitus
      are not risk factors for branch retinal vein occlusion.

PMID- 9196929
TI  - Axial length as a risk factor to branch retinal vein occlusion.
AB  - PURPOSE: To determine whether axial length is a factor in branch retinal vein
      occlusion. METHODS: Axial length measurements in a group of 24 patients with a
      unilateral branch retinal vein occlusion were compared with the axial length
      measurements in a control group. Axial length measurements were taken with an A
      scan; affected and unaffected eyes were measured. The control group consisted of
      24 individuals who matched the patients in the branch retinal vein occlusion
      group in age, systemic hypertension status, and diabetes mellitus status.
      RESULTS: The affected and fellow eye in patients in the branch retinal vein
      occlusion group did not differ statistically in axial length (P = 0.26). The mean
      axial length of affected eyes in the branch retinal vein occlusion group was
      22.76 +/- 0.92 mm, and the mean axial length of control eyes was 23.36 +/- 1.08
      mm. The difference in axial length between the eyes with a branch retinal vein
      occlusion and the eyes in the control group was statistically significant (P =
      0.023). CONCLUSION: The axial length of affected eyes of patients with branch
      retinal vein occlusion was on average 0.60 mm shorter than that of eyes of
      matched controls (95% confidence interval, 0.30-0.90 mm). The shorter axial
      length could be a local risk factor in the pathogenesis of a branch retinal vein
      occlusion.

PMID- 9196930
TI  - Significance of refractive status in branch retinal vein occlusion. A case
      control study.
AB  - PURPOSE: To evaluate the significance of refractive error in cases of branch
      retinal vein occlusion. METHODS: Of 354 patients with branch retinal vein
      occlusion who attended our clinic between 1989 and 1995, 75 patients with
      unilateral branch retinal vein occlusion were compared with an equal number of
      matched controls with similar inclusion and exclusion criteria. The spherical
      equivalents of the refractive errors of patients in both groups were compared
      using the chi-square test, student's t test, and multivariate logistic
      regression. RESULTS: Hypermetropia was present in 53 patients with branch retinal
      vein occlusion (70.7%) and in 33 control patients (44.0%; P = 0.0001). Myopia was
      present in 11 patients with branch retinal vein occlusion (14.7%) and in 30
      controls (40.0%; P = 0.0005). Emmetropia was present in 11 patients with branch
      retinal vein occlusion (14.7%) and in 12 controls (16.0%; P = 0.820). The odds
      ratio of developing branch retinal vein occlusion among patients with
      hypermetropia was 3.42 (95% Confidence Interval [CI], 1.62-7.2; P = 0.001) when
      compared with patients with no hypermetropia and 5.3 (95% CI, 2.1-13.3; P =
      0.0003) when compared with patients with myopia alone. CONCLUSION: Hypermetropia
      is significantly more common in patients with branch retinal vein occlusion than
      in the general population, whereas myopia is significantly less common in these
      patients.

PMID- 9196931
TI  - Ring retinal pigment epithelial window defect of the macula in central serous
      chorioretinopathy.
AB  - PURPOSE: Central serous chorioretinopathy is usually a benign disorder, in which
      resolution of serous subretinal fluid and return to a visual acuity of 20/40 or
      better is the normal outcome. In unusual cases of central serous
      chorioretinopathy, chronic subretinal fluid can lead to permanent retinal pigment
      epithelial depigmentation. In this report, we describe a ring-like (bull's eye)
      pattern of retinal pigment epithelial atrophy associated with central serous
      chorioretinopathy. METHODS: We examined eight patients (nine eyes) with central
      serous chorioretinopathy in whom retinal pigment epithelial window defects
      encircling the fovea developed. RESULTS: The average duration of symptoms before
      recognition of a circular window defect was 6 years. Visual acuity at the time of
      documentation of the ring-like window defect was 20/40 or worse in seven of nine
      (77%) eyes. Although laser photocoagulation treatment was performed in six of the
      nine eyes, vision improved two or more lines in only one eye (17%). CONCLUSION:
      Chronic central serous chorioretinopathy can cause a ring-like (bull's eye)
      pattern of retinal pigment epithelial window defects encircling the fovea. This
      pattern of retinal pigment epithelial window defect when seen in patients with
      central serous chorioretinopathy may indicate that a patient has a more severe
      form of central serous chorioretinopathy.

PMID- 9196932
TI  - Early versus late staining of microaneurysms in fluorescein angiography.
AB  - PURPOSE: To analyze the appearance and disappearance of microaneurysms in
      different phases of fluorescein angiography. METHODS: Three fluorescein
      angiograms were taken at 13-month intervals during a 26-month follow-up period
      from 13 patients with type I diabetes and mild background retinopathy. Two frames
      of the angiogram were analyzed: one from the transit phase and the other from the
      late phase of the angiogram. Individual microaneurysms were identified and
      localized from each frame using a computerized system for retrieval of the
      coordinates for each microaneurysm. Microaneurysms identified by their location
      then were analyzed in relation to the phase of the angiogram in which they were
      visualized and their disappearance during follow-up study. RESULTS: Thirty-three
      percent of the microaneurysms were visualized only in the early phase, 31% in
      only the late phase, and 36% in both phases of the fluorescein angiogram. The
      microaneurysms frequently changed their phase of appearance in the angiogram
      during follow-up study. CONCLUSION: During the 26-month follow-up period, between
      55% and 80% of the microaneurysms present at baseline disappeared. The phase of
      the baseline angiogram in which the microaneurysms were visualized did not
      determine their disappearance rate.

PMID- 9196933
TI  - Macular pattern dystrophy in patients with deafness and diabetes.
AB  - PURPOSE: To report the characteristic findings of a macular pattern dystrophy in
      patients with diabetes and deafness resulting from the mitochondrial point
      mutation at position 3243 and to expand the clinical spectrum of this condition
      by describing functional testing results. METHODS: Four diabetic patients who
      were referred to the eye department for diabetic fundus examination were found to
      harbor a macular pattern dystrophy. Further examination of visual fields; color
      contrast sensitivity; and the ear, nose, and throat; and molecular analysis of
      the mitochondrial genome were performed. Two of our patients were sisters. Their
      relatives also were examined. RESULTS: All four patients were found to harbor the
      mitochondrial point mutation at position 3243 and presented clinically with the
      phenotype of diabetes and deafness. The macular pattern dystrophy described in
      these patients seems to be typical for this condition. Results of a 9-year follow
      up study of one of the patients showed mild progression of atrophic changes. The
      overall prognosis of the retinopathy is likely to be good. CONCLUSION: These
      cases demonstrate the need for further molecular investigations when a macular
      pattern dystrophy is found in a patient with diabetes and deafness.

PMID- 9196934
TI  - Efficacy of dorzolamide hydrochloride in the management of chronic cystoid
      macular edema in patients with retinitis pigmentosa.
AB  - PURPOSE: To compare the effectiveness of topical dorzolamide hydrochloride
      (Trusopt, Merck and Co., Inc., West Point, PA), a carbonic anhydrase inhibitor,
      with that of oral acetazolamide (Diamox; Lederle Laboratories, Pearl River, NY)
      for the management of chronic cystoid macular edema in patients with retinitis
      pigmentosa. METHODS: A prospective, double-masked, crossover study was conducted
      in five patients with retinitis pigmentosa who had chronic cystoid macular edema.
      After baseline visual acuity was measured and a fluorescein angiogram was
      obtained, each patient was randomly assigned to receive either topical
      dorzolamide or a placebo for 4 weeks, followed by a crossover for the same
      period. Oral acetazolamide then was given separately to each patient for 2 weeks.
      Each phase of the study was followed by a washout period of 4 weeks, during which
      the patient was taken off all medications. At each visit, best corrected visual
      acuity was measured, a fluorescein angiogram was obtained, a subjective
      assessment of the effects on visual function, and any side effects of the
      medication or placebo were recorded in the form of a questionnaire by an
      independent observer. RESULTS: Compared with baseline or placebo values, there
      was no measurable improvement in visual acuity on the Early Treatment Diabetic
      Retinopathy Study charts with dorzolamide in any of the patients. The visual
      acuity in three of five patients, however, improved by seven letters or more with
      acetazolamide. Compared again with baseline or placebo values, fluorescein
      angiograms of two of five patients showed improvement in macular edema in both
      eyes with the use of dorzolamide, whereas all five showed improvement with
      acetazolamide. The improvement in macular edema was more marked with
      acetazolamide than with dorzolamide. The effect of dorzolamide given three times
      a day was the same as that when it was given five times a day. One patient
      indicated that dorzolamide was more effective than acetazolamide in improving
      visual function, three of five patients believed that acetazolamide was more
      effective, and one felt that both were equally effective. CONCLUSION: Dorzolamide
      provided improvement in cases of macular edema on fluorescein angiograms and
      subjective improvement of visual function in some patients with retinitis
      pigmentosa with cystoid macular edema. However, there was no measurable
      improvement in visual acuity with the topical use of this drug. Oral
      acetazolamide was found to be more effective than dorzolamide in managing macular
      edema and improving visual acuity.

PMID- 9196935
TI  - Histologic study of a shielded macula.
AB  - PURPOSE: To illustrate the histologic changes at the macula of an eye shielded
      from focused light for 76 years. Age-related macular degeneration with a central,
      subretinal, fibrous scar was present in the fellow eye. METHODS: Autopsy
      examination of both eyes of a 91-year-old man was performed. The superior half of
      the macular area of the shielded eye was studied by light microscopy, and the
      inferior half was studied by electron microscopy. Serial sections through the
      macular area of the fellow eye were prepared and studied. RESULTS: The shielded
      eye contained basal laminar deposits up to 6.0 microns in thickness and basal
      linear deposits up to 1.0 micron in thickness in the macular area. The
      photoreceptor outer and inner segments of the outer nuclear layer were intact.
      The macular area of the fellow eye contained a two-component, vascularized,
      disciform scar that measured up to 250 microns in one area, with retinal pigment
      epithelial tears at the nasal and temporal margins. Extensive photoreceptor layer
      atrophy was present. CONCLUSIONS: Such marked asymmetry of macular degeneration
      in this case may be further evidence of the role of light exposure in the
      development of age related macular degeneration.

PMID- 9196938
TI  - Traumatic retinopathy in Stargardt's disease.

PMID- 9196936
TI  - Complement-induced retinal arteriolar occlusions in the cat.
AB  - PURPOSE: To develop an animal model of complement-induced retinal vasculopathy
      and determine whether it resembles Purtscher's retinopathy. METHODS: Intravenous
      cobra venom factor was used to achieve intravascular activation of the complement
      system in cats. After a single bolus of cobra venom factor (75 units/kg), retinal
      blood flow was monitored at regular intervals by fluorescein angioscopy and
      angiography. RESULTS: Multiple small retinal arteriolar occlusions were present
      during the initial fluorescein transit of the immediate postinjection fluorescein
      study in 12 of 12 animals. Small, rapidly moving gaps in the fluorescein column
      were seen in two thirds of the animals observed continuously by fluorescein
      angioscopy. Angiographically, the obstructions were transient, and filling of the
      associated patches of capillary nonperfusion occurred within 3 minutes.
      Purtscher's-like ischemic retinal infarcts did not develop in any eye.
      Histopathologic analysis failed to demonstrate the nature of the transient
      vascular obstructive lesions, but indirect evidence suggested the possibility of
      granulocyte aggregates. CONCLUSION: Intravascular activation of the complement
      system produces transient microembolic retinal arteriolar occlusions in the cat.
      Although this model may represent a mild form of Purtscher's retinopathy, factors
      in addition to complement activation appear necessary to induce ischemic retinal
      infarcts.

PMID- 9196937
TI  - Diagnostic and therapeutic challenges.

PMID- 9196939
TI  - Spontaneous giant retinal pigment epithelial tear associated with panuveitis.

PMID- 9196940
TI  - Posttraumatic fungal endophthalmitis resulting from Scopulariopsis brevicaulis.

PMID- 9196941
TI  - Tumor-associated retinal pigment epithelial tears.

PMID- 9196942
TI  - Chronic postoperative gram-negative endophthalmitis.

PMID- 9196943
TI  - Case of rubeosis in association with proliferative vitreoretinopathy (PVR)

PMID- 9196944
TI  - Disposable intraocular endoscope lens cleaner.

PMID- 9196945
TI  - Silicone oil removal: a simple technique.

PMID- 9196946
TI  - Resurgence of pediculosis capitis?

PMID- 9196948
TI  - A new species of Phyllobothrium, parasite from Rhinoptera javanica from Waltair
      Coast, Andhra Pradesh, India.
AB  - A new species of a cestode, belonging to genus Phyllobothrium, obtained from
      spiral valve of the intestine of the elasmobranch Rhinoptera javanica is
      described. It shows remarkable differences from other known species of
      Phyllobothrium in having big scolex, bifurced and sessile nature of bothridia,
      testes number and nature of proglottids. The new species is designated as
      Phyllobothrium rhinoptera.

PMID- 9196947
TI  - [Regional analysis of human and animal hydatidosis in Chile, 1989-1993].
AB  - A descriptive study of hydatidosis, a still very prevalent zoonosis in Chile, was
      carried out with information up to 1993. Both human and animal data were
      included, the last one based on more reliable information. Regional human
      distribution up to 1991 shows persistent high notification rates in the extreme
      south of the country, Aysen and Magallanes hospital discharges, more reliable
      than notified cases, adds the IX Region of Araucania to the high risk areas, join
      with more than 30 hospitalizations per 100,000 people in 1989. Mortality case
      rate suggests strongly a very high subnotification in all the regions, mainly in
      O'Higgins. This zoonosis affects predominantly, young and middle aged adults,
      with a similar sex distribution. Cattle infection has decreased in the last 20
      years, particularly in sheep. Proportion of infected dogs also tends to show a
      lowering trend in specific studies. It appears a strong need of a national
      program for controlling this zoonosis, to be initiated with an epidemiological
      evaluation by regions and centered in health education, dogs' infection control
      with treatment and better handling of slaughterhouses.

PMID- 9196949
TI  - [Seasonal infection by metacercaria of Diplostomum (Austrodiplostomum) mordax
      (Szidat and Nani, 1951) and Tylodelphys destructor Szidat and Nani, 1951 in the
      Chilean Silverside, Basilichthys australis Eigenmann, 1927 (Pisces:Atherinidae)
      in Lake Rinihue].
AB  - Between 1993 and 1994, 129 specimens of Basilichthys australis from Lake Rinihue
      (39 degrees 50 minutes S; 72 degrees 20 minutes W) in the south of Chile were
      examined, in order to determine the prevalence and mean intensity of infections
      by Diplostomum mordax and Tylodelphys destructor metacercariae in the brain of
      fishes. Prevalence and mean intensity of D. mordax and mean intensity of T.
      destructor not showed seasonal significant differences. Prevalence of T.
      destructor was higher in summer than in winter, spring and autumn. No association
      between intensity of infection by D. mordax and T. destructor and body condition
      of the host was observed.

PMID- 9196950
TI  - [Diagnosis in 1348 patients which consulted for a probable spider bite or insect
      sting].
AB  - Accumulate experience, from 1955 to 1995, in an outpatient university
      parasitology clinic in Santiago, with 1,384 patients referred from diverse public
      and private medical institutions because of a probable spider bite or insect
      stings, is presented. It is noteworthy that only 618 (44.7%) of consultations
      corresponded to clinical conditions originated by arthropods, whereas from the
      remaining 766, 612 (44.2%) were due to a bacterial, viral or parasitic etiology
      and 154 (11.1%) were caused by physical or chemical agents. Frequency of
      diagnosis was: loxoscelism 16.6%, spider bites (excluded Loxosceles laeta) 1.3%,
      scorpion sting 0.9%, tick stings 2.2%, insect bites 23.7%, impetigo 6.6%,
      folliculitis 11.3%, boil 22.7%, erysipelas 0.1%, pustula maligna 0.3%, herpes
      simplex 2.5, palpebral herpes zoster 0.3%, acute Chagas' disease 0.4%,
      angioneurotic edema 0.1%, ecchymosis 3.0, contact dermitis 7.8% and chemical
      dermitis 0.2%. These frequencies do not indicate the real occurrence of the
      diagnosed nosologies, but what happened in a specialized outpatient clinic
      dealing cheaply with parasitic diseases and arthropod envenomations. Description
      of relevant clinical features and epidemiological considerations of pathology
      observed, conjointly with differential diagnosis are presented.

PMID- 9196951
TI  - [Chagas disease: impact of Triatoma infestans control program in Alto del Carmen,
      Huasco Province, III Region Atacama, Chile].
AB  - A control program of Triatoma infestans has been carried out in Alto del Carmen,
      an endemic chagasic rural county in the III Region, Chile. The program started in
      1988 with an attack phase consisting in a masshouse spraying with residual
      insecticide, followed by an entomological surveillance phase with health
      education for community participation and vector detection in eventually
      reinfested houses. A yearly evaluation in 1992, 1993, 1994 and 1995 was carried
      out in order to determine the effectiveness of vector control activities. In
      1992, 24.1% of dwellings was infested, whereas in 1993, 1994 and 1995 the
      infestation rates were 3.9%, 2.8% and 4.0% respectively. The similar infestation
      rates found in 1993, 1994 and 1995 suggest passive dispersion of triatomas from
      areas without surveillance. Additionally, in 1994, 110 (16.0%) out of 688
      examined people resulted serologically positive. It is noteworthy that all of the
      children in the 0-4 year age group--born after the attack phase--resulted
      serologically negative. This fact may indicate the interruption of vectorial
      transmission of Chagas' disease in Alto del Carmen county. It is concluded that
      the control activities performed in the county constitute good strategies to the
      Nacional Program of Control of T. infestans, but for the success of such a
      program it is necessary to integrate the efforts of all endemic areas with an
      active community participation.

PMID- 9196952
TI  - [Sarcocystis sp. in the diaphragm of a domestic cat (Felis catus) from Valdivia,
      Chile].
AB  - During 1987, diaphragms of 24 domestic cats from the city of Valdivia, Chile,
      were examined. In one (3.7%) cat infection by cysts of Sarcocystis sp. was
      observed. This is the first report of feline muscular infection by Sarcocystis
      sp. in Chile.

PMID- 9196953
TI  - [Presence of protozoan parasites in Argentine Patogonian autochthonous fish].

PMID- 9196954
TI  - [A new host and taxonomic notes for Baerietta chilensis
      (Cestoda:Nematotaeniidae)].

PMID- 9196955
TI  - [Gastrointestinal parasitism in the common partridge (Nothoprocta perdicaria) in
      the Nuble Zone, Chile].
AB  - A study on gastrointestinal parasitism in wild chilean partridges (Nothoprocta
      perdicaria) in the Nuble province (Chile) determined that 75% of birds were
      infected. The species Capillaria caudinflata, Subulura suctoria, Aploparaksis
      tinamoui and oocysts of Eimeria sp. were observed.

PMID- 9196956
TI  - [Intestinal parasites in two periurban populations in La Plata, Argentina].
AB  - The prevalence of intestinal parasites was studied in two urban neighborhoods
      with different socioeconomic conditions in La Plata, Argentina. Age, sex, and
      environmental factors were considered. One hundred and one hundred one children
      up to 14 years old were examined by coproparasitologic analysis. Giardia lamblia
      was the most frequent species. Overall prevalences (73.0% and 54.4%), frequencies
      of polyparasitism (45.0% and 14.8%), and prevalences of helminthic infection
      (48.0% and 12.7%) were highest in the population having significantly inferior
      sanitary and environmental conditions. A correlation with age was observed. It is
      necessary to apply management practices for the control of enteroparasitoses, in
      accordance with the corresponding characteristics of the environmental and
      sociocultural ecosistem.

PMID- 9196957
TI  - [Intestinal parasite infections in a periurban community from the Province of
      Buenos Aires, Argentina].
AB  - A survey for intestinal parasites was performed on 38 individuals within the
      urban area of La Plata City (Province of Buenos Aires, Argentina). This community
      is composed of brick-factory workers who also live in the factory premises. An
      analysis for intestinal parasites was done on fecal samples collected serially
      and by means of anal swabs and thereafter preserved in formol solution. At the
      same time, the occurrence of the parasites under study as well as that of
      commensal organisms was investigated in water and soil samples within the factory
      environs. Information was also obtained from the members of this community as
      their age, sex, birthplace, and recent travels, either abroad or to the interior
      of Argentina. The prevalence of the pathogens and commensal parasites was 89.5%.
      The frequency of protozoans and helminths was: G. lamblia 26.3%, B. hominis
      65.8%, A. lumbricoides 7.9%, H. nana 2.6%, Uncinaria sp. 7.9%, S. stercoralis
      2.6% and E. vermicularis 42.1%. None of these parasite or commensal organisms
      were present in the water samples investigated. Four out of 20 soil samples
      analyzed contained parasitic elements: T. canis eggs (one), G. lamblia cysts
      (two) and A. lumbricoides eggs (one). These results indicated that most important
      factors causing such a high prevalence of coproparasites were the poor conditions
      of personal and community hygiene in combination with the frequent travels to the
      north and the northeast of the country, regions which are endemic parasitic
      areas. The implementation of programs on health education and communal sanitation
      would contribute in the control of this health problem.

PMID- 9196958
TI  - Primary care provision of specialist services.

PMID- 9196959
TI  - Telemedicine: 'communication' by any other name?

PMID- 9196960
TI  - Keeping the meningococcus out of the media.

PMID- 9196961
TI  - General practitioners as providers of minor surgery--a success story?
AB  - BACKGROUND: It is now recognized that many minor surgical procedures can be
      appropriately performed in a general practitioner setting; the government has
      introduced a list of minor operations, for which it is prepared to pay a limited
      fee, and it is now time to see whether this service can be expanded. AIM: To
      demonstrate that a group of general practitioners (GPs) with a particular
      interest in minor surgery can offer an expanded service both to their own
      patients and also to the patients of neighbouring colleagues, whether fundholding
      or non-fundholding, within a health authority area. METHOD: The West Kent Health
      Authority awarded a contract for 500 minor operations to a group practice of five
      GPs. At the end of the first year, 511 operations had been performed, and the
      results and implications are discussed. RESULTS: The target of 500 minor
      operations was met and passed in the first year. Thirty-five neighbouring GPs
      referred their patients directly. All were offered an initial appointment within
      one week and had their operation performed within one month, unless they had
      expressed a preference for an alternative date. Several unsuspected malignancies
      were discovered-no complications were recorded, patients' and referring doctors'
      satisfaction was high and the scheme was judged to have been a success in their
      eyes. CONCLUSION: GPs can provide an efficient, cost-effective minor surgery
      service, which is popular with patients and referring colleagues. Whether this is
      the way we wish to organize minor surgery in the future needs further discussion.

PMID- 9196962
TI  - Case-control study of GP attendance rates by suicide cases with or without a
      psychiatric history.
AB  - BACKGROUND: Targets for reduction in suicide deaths have been set against a
      background of an increasing number of people committing suicide. It is often
      assumed that a reduction can be effected by increasing the detection in primary
      care of patients at risk. This presupposes that there are indicators that enable
      suicide risk to be detected reliably. AIM: To compare the characteristics of
      those who commit suicide with an age- and sex-matched control group in terms of
      level of general practitioner attendance, diagnosis and pharmacological treatment
      of mental illness, and to compare those suicides with and without a psychiatric
      history in terms of general practitioner attendance and history of
      pharmacological treatment. METHOD: From a total of 48 deaths attributed to
      suicide and undetermined causes in the Forth Valley in 1993, general practice
      case notes were located for 41. Live controls were matched to index cases by age,
      sex and practice. Information on consultations, referrals to secondary care,
      medication and diagnoses in the previous 10 years was extracted from general
      practice and, for suicides, psychiatric case notes. RESULTS: Over the 10-year
      period, suicide patients attended their general practitioner at a higher level
      than control subjects. However, the number of suicide patients who attended their
      general practitioner in the month before their death did not differ in comparison
      with control subjects over a similar period. Suicide cases, in comparison with
      control subjects, were more likely to have received a psychiatric diagnosis from
      their general practitioner, been prescribed psychotropic medication and received
      referral to specialist mental health services. Those suicide patients with a
      psychiatric history had a significantly higher number of general practitioner
      consultations than those without a psychiatric history in four out of the five
      years preceding death. Those suicide patients without a psychiatric history did
      not differ significantly from control subjects on any of the variables assessed.
      CONCLUSION: For those people committing suicide who do not have a psychiatric
      history and whose consultation patterns do not differ from the norm, it is
      difficult to suggest how general practitioners might improve their detection of
      relevant suicidal risk factors. For those patients with a psychiatric history who
      commit suicide, until we have more detailed information regarding the specific
      content of general practitioner's consultations before death and how these
      differed from other consultations of the deceased, then it is premature to assume
      that general practitioners are failing to identify indicators of impending
      suicide.

PMID- 9196963
TI  - Influenza and influenza-like illness in general practice: drawing lessons for
      surveillance from a pilot study in Paris, France.
AB  - BACKGROUND: There are two types of inflenza surveillance techniques: qualitative
      laboratory-based surveillance and quantitative medical practice-based
      surveillance. The former is of great importance in isolating new strains of the
      virus, which helps in the decision-making process concerning the composition of
      the vaccine, and the latter provides estimates of morbidity, mortality or
      economic impact as a result of infection from the influenza virus. Rapid methods
      such as immunoflourescence (IF) or immunocapture assays (ICA) are now available
      for diagnosis of influenza infections. However, little is known about the use of
      these methods for influenza surveillance purposes. AIMS: To evaluate the
      feasibility of a rapid influenza diagnosis in ambulatory conditions, and to
      investigate the therapeutical outcomes of patients suffering from influenza-like
      illness (ILI) in relation to the virological diagnoses. METHOD: During the 1994
      1995 influenza season, 130 patients presenting with ILI symptoms (< 36 hours) to
      33 general practitioners (GPs) were included in a prospective study. Two nasal
      swabs and one throat swab per patient were collected and sent to the laboratory
      within 12 hours. Information concerning therapeutical outcomes was recorded
      during examination. Specimens were analysed using the immunofluorescence (IF)
      method and antigen immunocapture assay (ICA). RESULTS: Sixteen influenza A (12%)
      and 19 influenza B (15%) infections were diagnosed. The overall rate of influenza
      positive specimens was 17% in the pre-epidemic period and 31% during the epidemic
      (P = 0.1). The rates of usable specimens for IF assay, nasal ICA and throat ICA
      were 46%, 100% and 99% respectively. The combination of these three collections
      ensured a highly sensitive influenza virological diagnosis. There were no
      differences in therapeutical outcomes between the influenza positive and negative
      cases. The GPs prescribed antibiotics in 60% of the cases for a mean duration of
      7 days (+/- 1.2). The mean duration of sick leave was 3.4 days (+/- 1.6). Twelve
      patients (four influenza positive, eight influenza negative) had been vaccinated
      at the beginning of the winter. The practitioner's intuition concerning 'which
      patient should be tested for influenza virus' did not prove useful in improving
      the aptness of virological diagnoses in the field of influenza surveillance.
      CONCLUSION: The only way to estimate the true impact of influenza is to carry out
      a systematic virological sampling based on a sensitive clinical definition and
      using sensitive laboratory methods.

PMID- 9196964
TI  - Over-the-counter drugs and prescribing in general practice.
AB  - BACKGROUND: Both the government and the pharmaceutical industry are interested in
      increasing the use of over-the-counter (OTC) medicines. The reaction on the part
      of general practitioners is more circumspect. AIM: To investigate whether
      fundholding or dispensing status and patient exemption from, or prepayment of
      prescription charges influence the behaviour of general practitioners with
      respect to prescribing preparations otherwise available OTC. METHOD: Regression
      analysis of data for all 105 Lincolnshire practices for the fiscal year 1993-94,
      using the number of items prescribed by the practice that were also available OTC
      as the outcome variable. Comparison of Audit Commission Thematic Analysis of
      Prescribing (ACTAP) data for fundholders' and non-fundholders' OTC prescribing in
      the same year. RESULTS: The prescription of medicines otherwise available OTC is
      less likely when the practice is fundholding and more likely when the practice
      has dispensing status. Prescription of such medicines also increases as the
      proportion of patients exempt from, or having prepaid prescription charges
      increases.

PMID- 9196966
TI  - The pattern of clinical advice sought by general practitioners from a medical
      consultant in clinical biochemistry.
AB  - Clinical biochemistry departments can be a valuable source of clinical advice for
      further investigations and the need for referral to specialist clinics. This
      paper outlines the pattern of clinical advice sought by general practitioners in
      a district hospital setting, and addresses some of the issues regarding seeking
      such advice and the implications for continuing medical education and training.

PMID- 9196965
TI  - Mental health care training priorities in general practice.
AB  - BACKGROUND: Mental health problems constitute a large part of general
      practitioners' (GPs') work, for which they may have received little training
      beyond their undergraduate education. They continue to find themselves criticized
      in the literature over inadequate recognition and management of these problems.
      While there is concern about the effectiveness of continuing medical education
      (CME), educational needs assessment can improve the outcome of CME programmes.
      AIM: To assess GPs' perceived educational needs regarding mental health problems.
      METHODS: A questionnaire was developed, piloted and posted to GPs (n = 380) in
      the Lambeth, Southwark and Lewisham Family Health Services Authority (FHSA) area
      in south-east Thames. In addition to demographic data, the questionnaire asked
      practitioners to select from a list of 26 mental health topics those in which
      they would like further training, their preferred educational formats and
      timetabling, and willingness to attend for training. Two postal reminders were
      sent to non-respondents. Data were analysed using SPSS. RESULTS: Altogether, 62%
      (237/380) of the GPs responded. The range for the number of topics selected was
      from zero to 26 and the mode was 5. Most frequently selected topics were
      psychiatric emergencies, somatization, counselling skills, 'heartsink' patients,
      psychosexual problems and stress management, each of which was chosen by at least
      40%. Small group work alone, and allied to a lecture, was rated as the most
      useful educational format. In all, 74% (175/237) indicated that they would be
      interested in attending a half-day training course. CONCLUSION: These results
      suggest that GPs working in the inner city recognize the importance of improving
      their skills in the care of mental health problems, and indicate which topics are
      regarded as the most important and suitable for educational interventions. A
      needs-led approach to continuing medical education of this kind will help to plan
      CME programmes relevant to GPs' needs.

PMID- 9196967
TI  - Knowledge about folic acid and the prevention of neural tube defects in two
      general practice populations.
AB  - Knowledge about the link between folic acid supplementation in pregnancy and the
      prevention of neural tube defects was assessed in women from two contrasting
      general practices using a questionnaire. The persisting lack of awareness,
      particularly in the more at-risk group from the inner city area, lends support to
      the argument in favour of the fortification of flour.

PMID- 9196968
TI  - A preliminary study to examine the adequacy of long-term treatment of depression
      and the extent of recovery in general practice.
AB  - About 1% of patients in general practice take antidepressants for long periods.
      Many receive repeat prescriptions, without review. It might be assumed that these
      patients are well and are on adequate maintenance treatment. Our findings refute
      this assumption; of 78 patients on long-term repeats, only a third were in
      remission and a fifth had Beck Depression Inventory scores suggesting persisting
      syndromal major depression. Subtherapeutic dosing of classic tricyclics was the
      norm rather than the exception. Patients on long term antidepressant treatment
      need regular review and adequate treatment to ensure remission is maintained.

PMID- 9196970
TI  - Giving feedback to questionnaire responders--an essential task?
AB  - Giving a quick feedback to responders of questionnaires, indicating how
      responders' views are similar to or different from the views expressed by their
      peers, could be considered good practice. It is relatively easy to produce
      feedback by using the research database and mail-merging a document with
      conventional word-processing software. Producing this type of feedback is likely
      to increase the respondent's involvement in a project and may even improve the
      quality of response.

PMID- 9196971
TI  - James Mackenzie Lecture 1996. Shaping our ends: the ethics of respect in a well
      led NHS.

PMID- 9196972
TI  - Spirometry in general practice.

PMID- 9196969
TI  - Benign prostatic hyperplasia.
AB  - The clinical syndrome of benign prostatic hyperplasia reflects a complex
      interplay between benign prostatic enlargement, which will affect almost all men
      by the age of 80, and the resulting outlet obstruction and lower urinary tract
      symptoms. The disease is now known to adversely affect the quality of life of
      around one man in three over the age of 50. New medical treatments and new
      surgical interventions are challenging the previous standard treatment of
      transurethral resection of prostate, which continues to have a morbidity of 17%
      and some mortality. Primary care will be increasingly involved in shared care
      with particular emphasis on monitoring of patients on watchful waiting medical
      therapy- and following operative intervention.

PMID- 9196973
TI  - Taking patient histories.

PMID- 9196974
TI  - Do GPs agree with 'old' sensible drinking limits?

PMID- 9196975
TI  - Breastfeeding and health in the western World.

PMID- 9196976
TI  - Repeat prescribing.

PMID- 9196977
TI  - Symphysis pubis dysfunction.

PMID- 9196978
TI  - Defeat depression.

PMID- 9196979
TI  - Reflux under the spotlight.

PMID- 9196980
TI  - An acutely disturbed woman.

PMID- 9196981
TI  - IBD: diagnosis and control.

PMID- 9196982
TI  - A GP guide to managing piles.

PMID- 9196983
TI  - Highlights of the year in gastroenterology.
AB  - The past 12 months have been a period of steady progress in the field of
      gastroenterology. Helicobacter pylori continues to dominate many areas of
      clinical research and the indications for eradication are increasing. A potent,
      topically-acting corticosteroid for Crohn's disease, and new hope and potential
      treatments for IBS sufferers are other developments.

PMID- 9196984
TI  - Current management of colorectal cancer.

PMID- 9196985
TI  - Matching the treatment to the patient in hypertension.

PMID- 9196986
TI  - Helping with obstructive sleep apnoea.

PMID- 9196987
TI  - The patient with shoulder problems.

PMID- 9196988
TI  - The MRCGP oral exams. Part one.

PMID- 9196989
TI  - [Cardiovascular risk factors in healthy adult men: influence of physical activity
      and dietary habits].
AB  - OBJECTIVE: To study the influence of physical activity and certain dietary habits
      on cardiovascular risk factors in middle age men. DESIGN: Prospective cross
      sectional study. SETTING: Primary care. SUBJECTS: Healthy male workers
      participating in a preventive medical examination. INTERVENTIONS: All
      participants were subjected to a physical activity inquiry, dietary recall,
      inquiry about smoking habits and anthropometric assessment. Also, blood pressure
      was measured and a fasting blood sample was obtained to assess serum total and
      HDL cholesterol, triglycerides and blood glucose. Multiple stepwise and canonical
      regressions were used to analyze data. RESULTS: Four hundred eleven subjects aged
      46.8 +/- 10 years old were studied. Twenty four percent smoked, mean body mass
      index was 26.2 +/- 2.6, mean calorie intake was 11.7 +/- 3 MJ/day and mean
      calorie expenditure 10.6 +/- 1.1 MJ/day or 1.52 +/- 0.13 times the resting
      metabolic rate. Physical activity, body mass index and fiber intake appeared as
      independent but weak predictors of total and LDL cholesterol. Alcohol intake, age
      and body mass index were predictors of HDL cholesterol and blood pressure was
      predicted by age, fiber intake and body mass index. Canonical analysis showed
      that 54% of blood pressure variation is explained by age, body mass index and
      fiber intake and that 31% of HDL cholesterol variation is explained by alcohol
      intake. CONCLUSIONS: Physical activity has a weak influence on serum total and
      LDL cholesterol. Alcohol intake is the main predictor of HDL cholesterol in these
      workers.

PMID- 9196990
TI  - [Intraoperative monitoring of gastric intramucosal pH].
AB  - BACKGROUND: Gastric mucosal pH may be a good indicator of splanchnic tissue
      oxygenation. AIM: To study the effects of abdominal surgical procedures on
      gastric mucosal pH. PATIENTS AND METHODS: Eighteen patients subjected to
      abdominal surgery were studied. All patients received general anesthesia and
      hemodynamic parameters were maintained within 20% of basal values. A tonometer
      was placed in the stomach after induction of anesthesia. Arterial blood gases and
      samples from the tonometer were obtained 30 minutes after induction and at 2
      hours of surgery. Intramucosal pH was calculated using Henderson-Haselbach
      equations. RESULTS: Basal gastric mucosal pH was 7.4 +/- 0.1 and did not change
      during surgery. Two patients had a pH persistently below 7.35 without hemodynamic
      alterations or systemic acidosis. CONCLUSIONS: Gastric mucosal pH is not modified
      by abdominal surgery and some patients have low values despite the absence of
      hemodynamic derangement.

PMID- 9196991
TI  - [Effect of pregnancy and lactation on the nutritional status of essential fatty
      acids in rat].
AB  - BACKGROUND: Pregnancy and lactation could be high risk situations for the
      development of essential fatty acid deficiencies. AIM: To study the effect of
      pregnancy and lactation on red blood cell phospholipids percentual fatty acid
      composition of virgin, pregnant and lactating rats. MATERIALS AND METHODS: Twenty
      four pregnant rats of 50 +/- 1 days of age were supplement with soy and 24 with
      fish oil during 21 days. Twelve rats of each group were sacrificed after 18 days
      of lactation, twenty four non pregnant rats received soy oil and acted as
      controls of pregnant and lactating rats. Red blood cell phospholipid fatty acid
      composition was analyzed by gas chromatography. RESULTS: The percentage of total
      omega-6 fatty acids of red blood cell phospholipid was 37.8 +/- 5.9, 32.6 +/- 0.6
      and 38.3 +/- 3.5% in non pregnant, pregnant and lactating rats respectively (p <
      0.001). The figures for total omega-3 fatty acids were 6.33 +/- 1.52, 4.31 +/-
      0.39 and 2.7 +/- 0.46 respectively (p < 0.001). There was no change in
      eicosatrienoic fatty acid percentage. Supplementation with fish oil reverted the
      decrease in omega-6 and omega-3 fatty acid percentage of pregnant and lactating
      rats. CONCLUSIONS: Pregnancy and lactation decrease the capacity to transform
      precursors of essential fatty acids in long chain polyunsaturated fatty acids.

PMID- 9196992
TI  - [Insulin tolerance test. A useful test to determine insulin resistance in obese
      hyperandrogenic women].
AB  - BACKGROUND: Insulin tolerance test is a simple method to measure insulin
      resistance that has a good correlation with glucose clamp studies. AIM: To use
      the insulin tolerance test to detect differences in insulin sensitivity between
      healthy and obese hyperandrogenic women and to correlate its results with those
      of the minimal model intravenous glucose tolerance test. PATIENTS AND METHODS:
      Five healthy women aged 27 +/- 7 years old with a body mass index of 21 +/- 2
      kg/m2 and six hyperandrogenic women aged 25 +/- 4 years old with a body mass
      index of 40 +/- 5 kg/m2 were studied after a 10 hours fast. For the insulin
      tolerance test 0.1 U/kg of crystalline insulin were injected intravenously and
      blood samples were drawn to measure glucose at -5,0,3,5,10 and 15 min. after the
      injection. Insulin resistance was calculated using the slope of descending blood
      glucose levels (SI1). For the intravenous glucose tolerance test, 29 blood
      glucose samples were obtained after an intravenous injection of 0.3 g glucose/kg
      followed by an injection of 0.02 U/kg of crystalline insulin. Insulin sensitivity
      (SI2) was calculated using Bergman's minimal model. RESULTS: Healthy women had a
      SI1 of 0.58 (range 0.53-0.63) and a SI2 of 7.9 x 10(-4) x min-1/microU/ml (range
      4.15-9.11). For hyperandrogenic women were 0.18 (range 0.06-0.29) and 0.9 x 10(
      4) x min-1/microU/ml (range 0.46-1.79), respectively. Both methods had a positive
      correlation coefficient of 0.859 (p < 0.001). CONCLUSIONS: Insulin tolerance test
      is a good method to measure insulin resistance and has a good correlation with
      the frequently sampled intravenous glucose tolerance test.

PMID- 9196993
TI  - [Acute kidney failure in patients with and without sepsis: prognosis and clinical
      course].
AB  - The purpose of this prospective study was to determine whether the course and
      prognosis of acute renal failure (ARF) in patients with and without sepsis are
      different. Two hundred fifty-two (8%) of 3086 consecutive patients admitted to a
      medical-surgical intensive care unit (ICU) developed ARE. One hundred forty-nine
      (59%) were septic and 103 (41%) were non-septic. No differences were found
      between groups regarding the incidence of oliguria, hyperkalemia,
      hypercatabolism, gastrointestinal bleeding, duration of oligria and renal
      deficit, severity of axotemia, dialysis requirements and duration of stay in the
      hospital. There were statistically significant differences between septic and non
      septic patients with respect of hyponatremia (67.8 vs 54.4%, p < 0.04),
      respiratory failure (68 vs 54%, p < 0.04), and thrombocytopenia (64 vs 48%, p <
      0.02). Mortality in septic patients was higher than in non-septics (56 vs 42.7%,
      p < 0.009). Factors associated with increased mortality in ARF septic patients
      were respiratory failure, metabolic acidosis and oliguria while in the non
      septics they were hepatic dysfunction, hyperkalemia, respiratory failure and
      infection acquired during the course of renal failure. We conclude that ARF
      developing in septic patients has a higher mortality than that of non-septic
      patients, whereas the incidence of hypercatabolism and oliguria was not different
      between both groups.

PMID- 9196994
TI  - [Hepatitis E virus infection in Chile: preliminary report].
AB  - BACKGROUND: Hepatitis E virus is an enterally transmitted virus that produces an
      acute self limited infection. AIM: To study serum antibodies against hepatitis E
      virus in different patients. PATIENTS AND METHODS: Using and ELISA technique, IgG
      antibodies against hepatitis E virus were measured in 40 alcoholics, 40
      hemophiliacs, 174 blood donors, 36 subjects with acute non A-non B-non C
      hepatitis and 66 subjects with acute hepatitis A. RESULTS: Antibodies were
      detected in one alcoholic (2.5%), 3 hemophiliacs (7.5%), 7 blood donors (4%), 3
      patients with non A-non B-non C hepatitis (8.3%) and 3 patients with acute
      hepatitis A (4.5%). CONCLUSIONS: A low frequency of hepatitis E infection was
      detected in the studied subjects.

PMID- 9196995
TI  - [Management of patients with severe pneumonia in mechanical ventilation:
      usefulness of bronchoalveolar lavage].
AB  - Bacterial pneumonia is a frequent complication in patients requiring mechanical
      ventilation (9-21%) and carries a significant mortality. The optimal management
      of these patients remains controversial. Some investigators have advocated
      invasive diagnostic testing using bronchoscopic techniques. AIM: To asses the
      diagnostic value of bronchoalveolar lavage (BAL) in patients with suspicion of
      bacterial pneumonia in mechanical ventilation. PATIENTS: We evaluated 73
      community-acquired pneumonia and 94 nosocomial pneumonia in critically ill and
      mechanically ventilated patients. RESULTS: The mortality was 50% (82 patients)
      and the principal death's cause was pulmonary sepsis (90%). 157 subjects received
      antibiotics before the microbiologic exam (94%) and 30 patients had multiple
      organ failure (MOF). Seventy of 167 BAL culture samples demonstrated microbial
      growth of > 10(4) cfu/ml (sensitivity: 41.9%). BAL culture samples isolated gram
      positive cocci in 27 cases (39%), aerobic gram-negative bacilli in 39 cases (57%)
      and P carinii in 3 cases (4%). Correlation between BAL culture and hemocultive
      results was very insignificant. Prognosis of community-acquired pneumonia and
      nosocomial pneumonia were very bad in both cases. Mortality of patients with MOF
      (73%) was higher than patients without MOF (44.8%), (p < 0.01). Mortality was
      similar in patients with BAL culture positive (48.6%) and negative (49.5%). The
      mortality rate of severe pneumonia in MV was very elevated and the BAL culture
      results didn't affect significantly the survival.

PMID- 9196996
TI  - [Predictor indices of early extubation in mechanical ventilation in patients
      treated with heart surgery].
AB  - BACKGROUND: Following open heart surgery, most patients are ventilated for 12 to
      24 hours to obtain a period of hemodynamic stability and to reduce the work of
      breathing. Some authors have proposed criteria to guide early extubation and have
      proposed physiologic parameters to predict which patients will be able to breathe
      spontaneously. AIM: To study the capacity to predict successful early extubation
      of ventilatory and gas exchange parameters. PATIENTS AND METHODS: Two hundred
      thirty patients admitted to an intensive care unit after coronary or valvular
      surgery were studied. Measurements were made through a T piece 30 minutes after
      discontinuing mechanical ventilation. RESULTS: Six patients died in the
      postoperative period. Two hundred ten patients tolerated early extubation (14 +/-
      5 h of mechanical ventilation) and 20 required prolonged mechanical ventilation
      (74 +/- 107 h). The latter had longer surgical procedures (291 +/- 65 and 240 +/-
      67 min respectively) and extracorporeal circulation times (138 +/- 42 and 104 +/-
      43 min respectively), required more vasoactive drugs, had more episodes of
      confusion and had a higher surgical risk. Tidal volume, respiratory frequency,
      maximal inspiratory pressure and blood gases at the moment of extubation were
      similar in both groups. CONCLUSIONS: Pulmonary function parameters and blood
      gases measured during a T piece trial are not good predictors of early extubation
      in cardiac surgery.

PMID- 9196997
TI  - [Tropisetron for the prevention of nausea and vomiting during chemotherapy:
      multicenter clinical study].
AB  - The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men,
      30 women) receiving cisplatin in doses of 75 mg/m2 or higher. On 279 chemotherapy
      cycles studied (max 6 per patient) 5 mg of tropisetron was administered once a
      day i.v on day 1 and p.o. on days 2 to 6. Efficacy preventing vomiting and nausea
      was measured in 24 hour period as: complete control O episodes, major control 1
      to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes.
      Satisfactory vomiting control (complete and major) was 69%, 63%, 82%, 88%, 96%
      and 96% in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and
      major) for the same days was 70%, 66%, 72%, 85%, 92% and 97%. Similar data was
      obtained for the subsequent cycles. Complete vomiting control was obtained in
      47%, 35%, 56%, 72%, 81% and 84% and for nausea in 42%, 39%, 48%, 64%, 81% and
      87%. 19 patients presented adverse effects (19.6%). Only 2 headache episodes had
      a definite relation with the antiemetic drug. 12 patients discontinued the
      medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to
      lack of collaboration, and 3 due to other reasons. We conclude that tropisetron
      allows satisfactory control of acute and delayed vomiting in a high percentage of
      patients treated with high doses of cisplatin. The drug does not have significant
      secondary effects. Tropisetron administration in only one daily dose implies an
      evident advantage and a treatment cost reduction.

PMID- 9196998
TI  - [Neuroborreliosis in Chile. Report of a child probably infected by imported
      pets].
AB  - Lyme disease, caused by the spirochete Borrelia burgdorferi, has several clinical
      manifestations and is transmitted to man by tick bites. In Chile and Latin
      America, several cases have been reported, but none with immunoblot confirmation
      or isolation of the infecting organism. We report a 9 year old boy consulting
      with bilateral facial palsy, polyradiculoneuritis with tetraparesis and meningeal
      irritation. Cerebrospinal fluid analysis showed increased protein concentration
      without pleocytosis and negative viral or bacterial cultures. IgM antibodies
      against Borrelia burgdorferi, were positive by ELISA and were confirmed by
      immunoblot at the Reference Laboratory of the University of Connecticut. The
      child had a recent contact with hamsters brought from Germany. The substantiation
      of Lyme disease existence in Chile should prompt the search and isolation of the
      causal agent.

PMID- 9196999
TI  - [Orthostatic tremor as a cause of difficulty in standing still].
AB  - Orthostatic tremor is characterized by a fine tremor of lower limb muscles that
      produces instability while standing still and alleviates on walking or sitting.
      We report two patients, aged 54 and 72 years old, in whom the tremor caused
      falls. The clinical features, a negative neurological examination, the
      alleviation on walking or sitting and the good response to clonazepam allowed the
      diagnosis. This disease should be considered in the differential diagnosis of
      standing still instability.

PMID- 9197000
TI  - [HIV infection: recommendations for the management of asymptomatic adults and of
      various clinical syndromes].
AB  - This paper presents recommendations on the care of HIV infected adults based upon
      the authors' personal experience with close to 700 patients in a
      multiprofessional pilot center. This medical care has 5 main objectives: 1)
      Promotion of good health (through standard recommendation of hygiene, health
      habits and regular checkups); 2) prevention of infectious complications (through
      detection of latent pathogens, chemoprophylaxis, vaccination and avoidance of
      risky exposures); 3) Treatment of complications (mainly infectious, through early
      diagnosis and proper treatment); 4) Delay of HIV disease progression (through
      timely and properly chosen antiretroviral therapy); 5) Reduction of HIV infection
      spread from index case to others (through promotion of responsible behavior and
      avoidance of pregnancy and HIV exposure to others). Studies for evaluating global
      health and immunologic status and carriage of potential pathogens are discussed
      as well as the criteria and timing for chemoprophylaxis for tuberculosis and P
      carinii pneumonia (PCP). Algorithms for the management of major clinical
      syndromes are presented: Diarrhea (afebrile, mostly parasitic, versus febrile,
      frequently bacterial); Pneumonia (lobar mostly bacterial versus interstitial,
      frequently PCP especially if lymphopenic and not receiving PCP prophylaxis);
      Brain mass lesion (most commonly toxoplasmosis). Finally, the evaluation and
      diagnostic possibilities of febrile patients is presented, based upon the
      immunologic status and associated symptoms.

PMID- 9197001
TI  - [Regulation of calcium and phosphorus metabolism].

PMID- 9197002
TI  - [Cellular basis of bone tissue development].

PMID- 9197003
TI  - [Molecular aspects of osteogenic phenomena].

PMID- 9197004
TI  - [Calcium requirements].

PMID- 9197005
TI  - [Bioavailability of ingested calcium].

PMID- 9197006
TI  - [Conditioning factors in bone mineralization].

PMID- 9197007
TI  - [Bone densitometry].

PMID- 9197008
TI  - [Biochemical markers of bone metabolism].

PMID- 9197009
TI  - [Epidemiology and clinical aspects of osteoporosis].

PMID- 9197010
TI  - [Prevention and treatment of osteoporosis].

PMID- 9197011
TI  - [Influence of nutrition and physical activity on bone mineralization].

PMID- 9197012
TI  - [Pediatric diseases that affect bone metabolism].

PMID- 9197013
TI  - [Alcohol, liver, and bone involvement. Hepatic osteodystrophy].

PMID- 9197014
TI  - [Food fortification with calcium].

PMID- 9197015
TI  - [Intervention of Campylobacter jejuni subsp. jejuni flagella in the adhesion to
      cellular cultures: bacteriological and immunological evidence].
AB  - The participation of the flagella of a virulent strain (O52) of Campylobacter
      jejuni subsp. jejuni in the adhesion to HEp-2 cells and their inhibition by means
      of homologous polyclonal antibodies, monoclonal anti-flagella antibodies and
      colostral natural antibodies (IgA) was studied. An aflagellated strain (T1) was
      used as negative control. Adhesion was observed in higher rates with O52 strain
      (72%) than with T1 strain (27.5%). Polyclonal, monoclonal and colostral
      antibodies inhibited O52 strain adhesion in more than 70% (p < 0.001). T1 strain
      adhesion was inhibited only by polyclonal and colostral natural antibodies. Our
      results suggest that the flagella of C. jejuni subsp. jejuni could participate
      effectively in the adhesion process. However, the inhibition of T1 strain by
      polyclonal and colostral antibodies suggests the existence of other binds of
      adhesins in the bacterial surface.

PMID- 9197016
TI  - [Urinary albumin excretion in non-insulin-dependent diabetic patients. Effects of
      an angiotensin-converting enzyme inhibitor].
AB  - BACKGROUND: Microalbuminuria in diabetic patients is diagnostic of early renal
      involvement and angiotensin converting enzyme inhibitors reduce albumin excretion
      in these subjects. AIM: To assess the effects of an angiotensin converting enzyme
      inhibitor on urinary albumin excretion in non insulin dependent diabetic
      patients. PATIENTS AND METHODS: Diabetic patients with normal blood pressure were
      randomly assigned to receive enalapril 10 mg/day or placebo and followed during
      18 months. Those with high blood pressure were randomly assigned to receive
      enalapril or acebutolol in doses necessary to normalize blood pressure and
      followed during 12 months. Every three months, urinary albumin excretion was
      measured in a four hour urine sample by radioimmunoassay. RESULTS: One hundred
      fifty two patients were recruited for the study and 46 were lost from follow up.
      In 17 subjects with normal blood pressure initial urinary albumin excretion below
      cutoff values (30 mg/24 h) and treated with enalapril, this parameter did not
      change; in 20 treated with placebo, it increased from 5.8 +/- 6.1 to 18.2 +/- 7.5
      mg/24 h. In 11 patients with normal pressure and increased initial urinary
      albumin, this parameter did not change with enalapril and increased in 10 with
      placebo from 87.3 +/- 75.1 to 253.6 +/- 61.1 mg/24 h. In hypertensive patients
      with normal urinary albumin excretion, no changes in this parameter were observed
      in those treated with acebutolol (n = 10) or enalapril (n = 14). In hypertensives
      with high urinary albumin excretion, it decreased from 119.2 +/- 8.5 to 40.0 +/-
      4.7 mg/24 h with enalapril treatment (n = 12), and no change was observed in
      those treated with acebutolol (n = 11). CONCLUSIONS: Enalapril decreases urinary
      albumin excretion in non insulin dependent diabetic patients.

PMID- 9197017
TI  - [Serum butyrylcholinesterase variants in eastern Santiago population].
AB  - BACKGROUND: Succinylcholine causes prolonged apneas in a proportion if subjects
      that have genetical defect of butyrylcholinesterase, due to the presence of
      unusual alleles in the locus BCHE. AIM: To estimate allele frequencies of three
      variants of serum butyrylcholinesterase, BCHE*U, BCHE*A and BCHE*F in an urban
      population of Santiago, Chile. SUBJECTS AND METHODS: Different phenotypes for the
      locus BCHE were determined in 300 blood samples coming from patients of a private
      clinical laboratory. The population was formed by an admixture of Amerindian and
      European (mostly Spanish) people. RESULTS: The frequency of BCHE*A was similar to
      that expected for this population, but BCHE*F frequency was greater than
      predicted. Eight subjects had the genotype BCHE AK. CONCLUSIONS: The higher
      frequency found for BCHE*F is probably due to the use of more precise detection
      techniques. Although the used method cannot distinguish BCHE UK from BCHE UU, the
      finding of individuals with BCHE AK, must lead to the suspicion that the
      frequency of the allele BCHE K is not negligible in Santiago.

PMID- 9197018
TI  - [Tripano-triatomine infection of Triatoma spinolai in a zone with epidemiological
      risk].
AB  - BACKGROUND: Triatoma spinolai is the only wild vector for Chagas disease in Chile
      and its epidemiological importance is being studied. AIM: To study the proportion
      of insects infected with Trypanosoma cruzi (tripano-triatomine index) in a zone
      with epidemiological risk in the Metropolitan Region of Chile. METHODS: Four
      hundred ninety two specimens of Triatoma spinolai were collected in four sites of
      a quarry zone, 14 kilometers north of Santiago. Their maturity and the presence
      of Trypanosoma cruzi in their intestinal contents were determined. RESULTS: Mean
      tripano-triatomine index was 26.02 +/- 2% (range 0 to 34% in different sites).
      The proportion of infected insects increased along with their maturity and 58% of
      adult specimens were infected. There was a seasonal variation of the proportion
      of infected specimens, being lower in March and June and higher in July and
      February. CONCLUSIONS: The studied zone has a potential epidemiological risk for
      the transmission of Chagas disease by Triatoma spinolai.

PMID- 9197019
TI  - [Food and nutrition knowledge of elementary and high school-age children from
      Chile's Metropolitan Region].
AB  - BACKGROUND: In Chile there is scarce food and nutrition knowledge among school
      age children. AIM: To determine the degree of food and nutrition knowledge of
      elementary and high school children and its relationship to socioeconomic status,
      sex, type of school and geographic area. SUBJECTS AND METHODS: Between 1986 and
      1987, a representative and proportional sample of 4509 children was chosen from
      the Metropolitan Region. This sample was stratified according to school grade,
      sex, type of school and geographical area. Graffar's modified method was used to
      measure socioeconomic status. Food and nutrition knowledge was assessed by a
      specific test for each grade, based on the objectives pursued by the curricular
      programs of the Ministry of Education. RESULTS: The test was applied to 4197
      children. Food and nutrition knowledge was significantly lower in the second
      subcycle of elementary school, in males, in older children from each grade, in
      rural areas, in children of low socioeconomic status and in public schools.
      CONCLUSIONS: School age children were unaware of fundamental aspects related to
      food and nutrition and curriculum programs of the Ministry of Education should be
      reformulated to overcome these deficiencies.

PMID- 9197020
TI  - [Impact of an educational manual on knowledge and attitudes of rheumatic patients
      and health care workers].
AB  - BACKGROUND: Education may induce voluntary behavioral changes in patients that
      lead to an improvement in health status. AIM: To assess the impact of the
      educational manual "Aches and Pain" on knowledge and attitudes of patients with
      chronic rheumatism and paramedics, using an instrument with 40 asseverations
      extracted from the manual. PATIENTS AND METHODS: Seventy seven patients and 42
      paramedics were studied. The assessment instrument was responded before and after
      reading chapters of the manual, selected by the authors. Knowledge was quantified
      according to the number of correct answers. Adaptation to disease, optimism and
      self help capacity were the evaluated attitudes, using a five point scale.
      RESULTS: The study was completed by 48 patients and 42 paramedics. Knowledge
      improved from 19.9 +/- 5.3 to 25.6 +/-6.15 correct answers in the former and from
      23.6 +/- 4.9 to 30.3 +/- 5.5 in the latter (p < 0.001). In patients there were
      improvements in the degree of adaptation to disease from 3.6 +/- 0.9 to 4.0 +/-
      0.8 and in self-help capacity from 4.0 +/- 0.8 to 4.3 +/- 0.8; optimism did not
      improve significantly. CONCLUSIONS: The educational manual had an impact on
      knowledge and improved rheumatic patient's attitudes towards the disease.

PMID- 9197021
TI  - [Subjective and objective evaluation of the results of laparoscopic antireflux
      surgery in patients with gastroesophageal reflux].
AB  - BACKGROUND: Laparoscopic antireflux surgery is a minimally invasive procedure
      that should have similar results than classical surgical treatment. AIM: To
      report the results of a prospective study of laparoscopic antireflux surgery in
      patients with gastroesophageal reflux. PATIENTS AND METHODS: Thirty two patients
      with gastroesophageal reflux and without Barret's esophagus, were subjected to
      endoscopy, manometry and measurement of intraesophageal pH before and after
      laparoscopic surgery. RESULTS: There were no postoperative deaths or
      complications. Gastroesophageal sphincter pressure and abdominal sphincter length
      increased from 9.1 +/- 3.9 to 13.0 +/- 3.5 mm Hg and from 8.1 +/- 6.2 to 13.5 +/-
      5.4 cm after surgery (p < 0.01). There was a decrease in acid reflux in 82% of
      patients. CONCLUSIONS: Laparoscopic antireflux surgery reproduces exactly the
      results of open surgical procedures.

PMID- 9197022
TI  - [Cardiovascular risk factors in 15 patients in chronic hemodialysis in Temuco
      city. Descriptive comparison with the general Chilean population].
AB  - BACKGROUND: Patients in chronic hemodialysis have a high mortality due to
      cardiovascular diseases. AIM: To study cardiovascular risk factors and
      nutritional status in a group of patients in maintenance hemodialysis. PATIENTS
      AND METHODS: Body mass index, blood pressure, serum levels of totals cholesterol,
      HDL cholesterol, triglycerides and albumin were measured in 15 patients (8 male)
      in maintenance hemodialysis. Data were compared with available figures for the
      normal Chilean population. RESULTS: Age ranged from 33 to 60 years old in female
      patients and from 22 to 63 years old in males. Thirteen subjects (87%) had high
      blood pressure, all had HDL cholesterol levels below 35 mg/dl, four (27%) had a
      total cholesterol over 200 mg/dl, three had triglyceride levels over 200 m/dl,
      two (13%) smoked and none were diabetic. Mean body mass index was normal, albumin
      levels were 4.16 and 4.02 g/dl and serum creatinine was 11.64 and 9.68 mg/dl in
      males and females respectively. The estimated prevalence of high blood pressure,
      hypercholesterolemia and smoking in the general Chilean population range from 9
      to 22%, from 50 to 52% and from 45 to 51% respectively. CONCLUSIONS: This group
      of patients has a high frequency of high blood pressure and low HDL cholesterol
      levels.

PMID- 9197023
TI  - [Protruding plaques of the thoracic aorta in the transesophageal echocardiogram:
      clinical and echographic characteristics].
AB  - BACKGROUND: Transesophageal echocardiography has a better sensitivity than
      conventional echocardiography for the detection of protruding atherosclerotic
      plaques of the thoracic aorta. AIM: To study the clinical and echographic
      features of protruding aortic plaques detected with transesophageal
      echocardiography. PATIENTS AND METHODS: Clinical histories of 308 patients
      subjected to transesophageal echocardiography were reviewed. Subjects with
      protruding aortic plaques > 0.5 cm were selected. RESULTS: Fifteen patients had
      protruding aortic plaques on transesophageal echocardiography and none of these
      were detected with conventional echocardiography. All these patients were in
      sinus rhythm and had high blood pressure. Ten subjects (67%) had a history of
      ischemic cerebrovascular or peripheral artery diseases (compared to 31% of
      subjects without protruding plaques) and in seven, the plaque was the only
      embolic source. Six patients (40%) smoked and 4 (27%) had coronary artery
      disease. One patient was diabetic and one had hypercholesterolemia. CONCLUSIONS:
      Transesophageal echocardiography allows the detection of protruding aortic
      plaques that are potential embolic sources in patients with vascular diseases.

PMID- 9197024
TI  - [Multiple endocrine neoplasia type 2A. Report of a case with an unusually
      aggressive outcome].
AB  - We report a 28 years old woman who consulted for diarrhea of two years and a
      thyroid nodule. A medullary thyroid carcinoma was diagnosed and a thyroidectomy
      performed. There was a local relapse two months later and distant metastases were
      found five months later. A MIBG-1131 scintigraphic image of the adrenals lead to
      the suspicion of a bilateral pheochromocytoma. The surgical resection of the
      adrenals confirmed the diagnosis. There was no response to chemotherapy and the
      patient continued with severe hypercalcemia, repeated infections, persistent
      diarrhea and cachexia, dying one year after the diagnosis. There was no family
      history of the disease. We conclude that this is a particularly aggressive
      presentation of a multiple endocrine neoplasia type 2A.

PMID- 9197025
TI  - [Asymptomatic elevation of plasmatic alkaline phosphatases secondary to benign
      familial hyperphosphatasemia in a patient].
AB  - We report a 33 years old male consulting for abdominal pain. Initial diagnostic
      work up showed high levels of alkaline phosphatases, that were confirmed in a new
      blood sample. Using electrophoresis, total alkaline phosphatases were 198 U/l
      (normal values = 30-117) and the bone fraction was 101 U/l (normal values =
      0.35). Bone scintiscan and endocrinological assessment were normal. One year
      later, the same values persisted. Studying the family, three of four brothers had
      the same alterations in alkaline phosphatases. It was concluded that these
      subjects had the rare condition known as benign familial hyperphosphatasemia.

PMID- 9197026
TI  - [Testosterone-producing adrenal carcinoma: report of 2 cases].
AB  - We report two women aged 48 and 65 years old with hirsutism and a painful
      abdominal mass. Laboratory assessment showed serum testosterone levels of 500 and
      321 ng/dl (normal values below 110 ng/ml). Abdominal CAT scans showed an adrenal
      mass in both patients. The younger woman was subjected to a surgical resection,
      the tumor relapsed two years later and the patient died. The other woman died
      during the first hospitalization. Adrenal tumors infrequently secrete
      testosterone as described in these two patients.

PMID- 9197028
TI  - [Androgen receptor gene structure and protein function. Gene structural defects
      that promote androgen resistance in men].
AB  - The human androgen receptor is a member of the superfamily of steroid hormone
      receptors and contains three functional domains: an amino-terminal region
      involved in the expression of androgen regulated genes, a central cysteine-rich
      DNA binding region and a carboxy-terminal hormone binding region. Proper
      functioning of this protein is a prerequisite for normal male sexual
      differentiation and development. Androgen action is currently studied in vitro,
      using fibroblasts culture from genital skin and complementary DNA of the androgen
      receptor gene has been recently cloned and sequenced. During recent years a
      substantial progress has been made elucidating the structure-function
      relationship of the androgen receptor and the characterization of the molecular
      defects associated with androgen insensitivity syndromes. There appears to be a
      broad correlation between the degree of receptor dysfunction caused by the
      mutation and the patient phenotype.

PMID- 9197027
TI  - [Renovascular hypertension. Radionuclide renography for detection and prediction
      of clinical response to revascularization].
AB  - The most frequently used non invasive tests in the diagnosis of renovascular
      hypertension are the measurement of peripheral blood renin before and after
      captopril administration, intravenous pyelogram, renal Doppler examination and
      radionuclide renography without and with angiotensin converting enzyme inhibitor
      administration. Measurement of renal vein renin levels and renal angiography are
      invasive tests commonly used. The latter allows an anatomical diagnosis of renal
      vein stenosis but does not give information about the functional consequences of
      such lesion and thus, does not predict the response of blood pressure to
      revascularization. Radionuclide renography has become the most useful non
      invasive diagnostic test, with a sensitivity and specificity of 83-94 and 85-97%
      respectively. It also predicts clinical response to revascularization and is
      useful for follow up after surgery or angioplasty. It also has good results in
      patients with renal failure, bilateral stenosis or stenosis in a solitary kidney
      and in transplanted patients.

PMID- 9197029
TI  - [Assessment of the use of statistical methods in health research].
AB  - BACKGROUND: Computer use has lead to a great development of statistical methods.
      AIM: To assess the use of statistical methods in Chilean medical literature.
      METHODS: Two hundred sixty four papers appeared in Revista Medica de Chile and
      Revista Chilena de Pediatria between 1983 and 1993 were reviewed. RESULTS:
      Student's "t", Fisher's, and chi 2 test are the most frequently used statistical
      methods in 67% of papers. Correlation coefficients are used in 10% of papers.
      Multivariate methods are seldom used. CONCLUSIONS: Statistical analysis of papers
      published in Chilean medical journals is restricted to very few methods.

PMID- 9197030
TI  - [Prevalence of Staphylococcus aureus among food handlers from a metropolitan
      university in Chile].
AB  - BACKGROUND: An important agent of food intoxication is Staphylococcus aureus,
      that is able to produce enterotoxins. AIM: To detect Staphylococcus aureus
      contamination in cafeteria food handlers of a Chilean University. SUBJECTS AND
      METHODS: Nose, throat, hands and nail samples from 87 food handlers were obtained
      for microbiological examination. RESULTS: Fifty seven subjects (65.5%) were
      carriers of Staphylococcus aureus. Enterotoxigenic Staphylococcus aureus was
      found in 36 subjects (41%). The most frequently found enterotoxin was type B (18
      samples) followed by type D (12 samples). Men bad a higher frequency of
      contamination than women (83 and 57% of positive samples respectively).
      CONCLUSIONS: The frequency of Staphylococcus aureus contamination among food
      handlers is high and should prompt personal and environmental hygienic measures.

PMID- 9197031
TI  - [A visit to an internist in the year 2000].

PMID- 9197032
TI  - [Emergency of fluconazole-resistant infections by Candida krusei and Candida
      glabrata in neutropenic patients].

PMID- 9197033
TI  - [The fatal disease of Napoleon Bonaparte].
AB  - Napoleon Bonaparte, soldier, general and emperor, desired the European union. He
      abdicated twice and in 1814 was confined to Santa Helena island. From the
      biographic description of bis last exile, we have extracted a description of the
      disease that lead him to die. We postulate that he had a gastric lymphoma.

PMID- 9197034
TI  - Efficacy and effectiveness of treatment.

PMID- 9197035
TI  - Intraoperative ultrasonography of liver, bile ducts and pancreas.
AB  - The use of intraoperative ultrasonography (IOUS) to evaluate liver, bile ducts
      and pancreatic disease, as compared to the results of preoperative
      ultrasonography and CT, is discussed. Forty-two patients who underwent abdominal
      surgery for suspected hepatobiliary and/or pancreatic diseases were studied. The
      intraoperative study was carried out with a portable apparatus (Aloka 500,
      Japan), using 5.0 MHz and 7.5 MHz linear sterile transducers. The main
      indications for IOUS were the search for and/or evaluation of primary hepatic
      masses, hepatic abscesses or metastases, obstructive jaundice, or neuroendocrine
      tumors. In 5 cases (38.5 percent) from the hepatobiliary group and in 7 cases
      (58.3 percent) from the pancreatic group, a difference between preoperative and
      intraoperative findings was observed. The main difference was observed in
      relation to the number and size of hepatic and pancreatic lesions. The
      relationship between the lesions and the vascular structures was evaluated
      through IOUS. The method was also used to guide surgical procedures such as
      biopsies, the alcoholization of nodules, and the drainage of abscesses. IOUS
      plays an important role in detecting small hepatic and pancreatic nodules. In the
      assessment of anatomical relationships between the lesions and the vascular
      structures, and in the performance of interventionist procedures.

PMID- 9197036
TI  - The Sexuality Project (Pro-Sex) of the Institute of Psychiatry of the HCFMUSP:
      first year of activities.
AB  - The results of one year of activities of a multidisciplinary staff comprised of
      five psychiatrists, one urologist, one gynecologist, and seven psychologists, who
      integrate the Sexuality Project (PRO-SEX) of the institute of Psychiatric.
      Hospital das Clinicas, College of Medicine, University of Sao Paulo (FMUSP), are
      presented. Different sexual disorders were evaluated and treated in 140 patients
      (116 men and 24 women). In addition, a standard protocol was established for the
      medical assistance of patients; four research projects have been initiated; and
      courses were offered to residents in psychiatry, urology, and obstetrics
      gynecology, as well as to undergraduate and postgraduate students of FMUSP. The
      PRO-SEX staff presented their research at one congress and two symposiums, and
      published four articles. Furthermore, an extensive program was established for
      1995 in order to continue the advanced medical study of human sexuality.

PMID- 9197038
TI  - Early diagnosis of melanoma by surface microscopy (dermatoscopy).
AB  - The main objective of surface microscopy is the early and accurate diagnosis of
      melanoma in its initial phases of evolution and infiltration. Since the
      development of the dermatoscope in the 1990's, surface microscopy has become a
      simple technique. Differential diagnosis of pigmented skin lesions can be
      achieved with a diagnostic sensitivity of about 90 percent, and the proper
      differentiation of pigmented melanocytic and non-melanocytic lesions, and
      malignant and benign melanocytic lesions, may also be safely determined.

PMID- 9197037
TI  - Nasal septal pediculate carcinoma in situ: differential diagnosis.
AB  - Pediculated lesions of the nasal cavities are relatively common in daily
      practice, and include inflammatory polyps, benign tumors (papillomas being the
      most common), malignant tumors, and specific processes, such as polypoid
      rhinosporidiosis. The authors describe a female patient with a warty,
      pediculated, and asymptomatic lesion in the nasal septal mucosa. The anatomo
      pathological exam showed this to be a "carcinoma in situ". The few bibliographic
      citations report only an association between the tumor and contact with wood
      dust, such as oak, ebony and beech. The patient was not exposed to these
      elements. It is important to emphasize the routine performance of a complete
      otolaryngological exam for patients seeking out specialists, in order to detect
      potentially malignant lesions whose early removal would permit a complete cure.

PMID- 9197039
TI  - Polycystic ovary syndrome: clinical and laboratory evaluation.
AB  - OBJECTIVE: To evaluate clinically, and with laboratory, tests, women with
      polycystic ovary syndrome (PCO). PATIENTS: One hundred and twelve women with PCO
      were studied. METHODS: The following data was recorded: Current age; age at
      menarche; menstrual irregularity, occurrence of similar cases in the family;
      fertility, obstetric history; body mass index (BMI); and presence of hirsutism.
      Serum measurements of follicle stimulating hormone (FSH), luteinizing hormone
      (LH), prolactin, free testosterone, and dehydroepiandrosterone sulfate were
      taken. RESULTS: All patients presented either oligomenorrhea (31 percent),
      periods of secondary amenorrhea (9 percent), or both alterations (60 percent).
      The majority of the patients were infertile (75.6 percent). The LH/FSH ratio was
      higher than 2:1 in 55 percent of the patients and higher than 3:1 in 26.2
      percent. The ultrasonographic aspect of the ovaries was considered to be normal
      in 31 percent. CONCLUSION: The main clinical feature of the PCO is the
      irregularity of menses since menarche, and that the laboratory tests would be
      important to exclude other disorders such as hyperprolactinemia or
      hyperandrogenemia caused by late-onset congenital adrenal hyperplasia.

PMID- 9197040
TI  - Arterial embolectomy in lower limbs.
AB  - Arterial embolisms in the lower limbs occur frequently, and are of great interest
      to the vascular surgeon. The authors studied 159 cases of arterial embolisms in
      lower limbs from January 1991 to July 1993. Ages varied from 12 to 98, with a
      mean of 58. Eighty patients were male and 78 were female. In most cases, etiology
      of the embolus was well-established, and mainly caused (78 percent) by atrial
      fibrillation. Occlusion was most frequent in the femoral artery (53.4 percent).
      All patients presented severe lower limb ischemia, but not gangrene, on
      admission. The duration of ischemia, between the onset of symptoms and the
      liberation of arterial flow, was in most patients (67.9 percent) less than 24
      hours. All patients were submitted to lower limb embolectomy with the Fogarty
      catheter, of which 70.9 percent were done through the femoral artery. Fasciotomy
      was performed on 48 patients due to a compartimental syndrome. Nineteen patients
      died immediately after operation; 68.4 percent due to heart failure. Twenty-three
      (16.4 percent) of the 140 surviving patients (150 operated limbs) were submitted
      to amputations after the occlusion of artery branches, which had undergone
      embolectomies. One hundred and twenty-seven limbs (84.6 percent) were preserved
      in 117 patients (83.5 percent). Eleven cases (7.3 percent) required repeated
      surgery with the Fogarty catheter. The patients with muscle tenderness,
      paralysis, or ischemia lasting longer than 24 hours had worse results in relation
      to the preservation of the limb (p < 0.05). We conclude that patients who present
      lower limb embolisms, are in good clinical condition, and who do not have any
      necrosis in the limbs, have good outcomes as to limb preservation, along with low
      complication rates, after embolectomy with the Fogarty catheter. Limb
      preservation was significantly higher in patients who did not present muscle
      tenderness, and who had normal motor activity and a ischemia duration of less
      than 24 hours.

PMID- 9197041
TI  - Excessive somnolence.
AB  - Excessive somnolence can be quite a incapacitating manifestation, and is
      frequently neglected by physicians and patients. This article reviews the
      determinant factors, the evaluation and quantification of diurnal somnolence, and
      the description and treatment of the main causes of excessive somnolence.

PMID- 9197042
TI  - Gallstone ileus as a cause of upper intestinal obstruction.
AB  - Gallstone ileus, a mechanical intestinal obstruction caused by the passage of a
      gallstone into the intestinal lumen through a fistula, although not common,
      deserves to more carefully studied due to its morbidity and mortality. Its
      incidence among older-age groups explains its association with chronic and
      degenerative diseases, which increase the complexity of the treatment choice. The
      need and appropriateness of a surgical approach to a cholecystenteric fistula to
      solve the obstructive emergency, in a one or two stage procedure, has been
      discussed in the literature. It has also been reported that gallstone ileus is an
      uncommon cause of upper intestinal obstruction. Intestinal obstruction is seen
      more frequently after a gallstone impacts at the ileocecal valve. The authors
      report a case of gallstone ileus as a cause of upper intestinal obstruction and
      discuss its diagnosis and treatment.

PMID- 9197043
TI  - Unlimited power (and other rich fantasies of researchers and clinicians)

PMID- 9197044
TI  - Family members' experiences with the nursing home placement of an older adult.
AB  - Although there is substantial literature available on a variety of aspects of
      nursing home placement, relatively little is known about the experiences of
      family members confronted with this challenge. This study involved in-depth
      interviews with nine adult family members within 2 weeks of the relocation of the
      older adult relative. Factors related to recognition of the need for placement,
      selection of a facility, managing the relocation, and effects of placement on the
      family decision-makers were explored. Results have significant implications for
      nursing practice related to the lack of advanced planning, needs for time and
      information, and supportive interventions.

PMID- 9197045
TI  - First-time mothers' perceptions of prenatal care services.
AB  - This study sought to uncover information regarding prenatal care services as
      reported by primiparas. Inadequate prenatal care has been linked with the
      delivery of low birth weight (LBW) infants and infant mortality. This secondary
      analysis of a larger study (N = 426) examined the need for and availability,
      accessibility, and use of prenatal care services by primiparas (n = 141). Results
      indicated that primiparas delivering LBW infants reported less satisfaction with
      information on birth control and less information on infant feeding. In addition,
      mothers of LBW infants reported more often than mothers of normal birthweight
      infants that transportation and finances were barriers to prenatal care.
      Childbirth preparation class was the only predictor variable for birth weight in
      this study.

PMID- 9197046
TI  - Rooming-in for elderly surgical patients.
AB  - Elderly patients are at risk for developing acute confusion during
      hospitalization. Rooming-in, an intervention frequently used for pediatric
      patients, was compared to usual care in a sample of 24 elderly patients
      hospitalized for orthopedic surgery. Although confusion during hospitalization,
      complicate rate, and length of stay did not differ between patients who did and
      did not have rooming-in, the family members and friends who roomed in were very
      satisfied with the experience. These findings suggest that rooming-in is feasible
      and highly satisfactory to the patient's family and/or friends.

PMID- 9197047
TI  - Angry? Let's talk about it!
AB  - Cognitive/perceptual, physiological, and behavioral correlates of anger
      discussion were examined in a sample of 461 health fair participants at a
      southeastern university. Subjects, who usually discussed their anger differed
      significantly from those who did not in systolic blood pressure, diastolic blood
      pressure, body mass index, aerobic exercise, perceived importance of health, and
      perceived health status. In gender-specific correlational analyses, discussion of
      anger was inversely related to women's global assessment of stress and to their
      levels of perceived stress at home and at work. This study suggests that talking
      about anger may be a health-promoting alternative to suppressing it or venting it
      outwardly after a provocation. Gender differences and implications for practice
      are discussed.

PMID- 9197048
TI  - Patients' use of health-teaching materials at three readability levels.
AB  - The extent to which patients use and learn from drug literature written at three
      different readability levels was examined. A two-way analysis of variance showed
      an interaction effect on knowledge score between the readability level of the
      leaflet and the amount of schooling subjects reported: persons with higher
      education learned most from the hardest pamphlet and persons with the least
      formal education learned the most from the easiest pamphlet. A similar
      interaction was found in testing the likelihood that patients had read the
      leaflet. The results suggest that persons with little formal education would
      benefit from teaching materials with a readability level considerably lower than
      even many "easy-to-read" health-teaching materials available today.

PMID- 9197049
TI  - Factors contributing to hope among noninstitutionalized elderly.
AB  - The purposes of this study were to describe the level of hope and to identify
      predictor variables associated with hope in adults over the age of 65 years.
      Using a descriptive correlational design, noninstitutionalized individuals (N =
      169; 67.5% female) ages 65 to 94 years (M = 75.4) were surveyed. Results showed a
      moderately high level of hope, suggesting that participants perceived a future
      that is good. A caring, health-promotion philosophy of practice, rather than an
      institutional philosophy of cure and treatment, may more actively support and
      enhance clients' hope. Social support, religious well-being, and health emerged
      as significant predictor variables in this study. Nursing interventions may
      influence these variables and, thus, enhance hope among noninstitutionalized
      elderly.

PMID- 9197050
TI  - Nurses as members of institutional review boards.

PMID- 9197051
TI  - Problems of the skin. Recognising the morbidity.

PMID- 9197052
TI  - Partnerships in practice.

PMID- 9197053
TI  - Primary skin infections.

PMID- 9197054
TI  - There is something wrong with my nail.
AB  - Nail problems are a frequent source of concern to patients and are a relatively
      common presenting complaint to general practitioners. While tinea unguium and
      psoriasis are the main causes of nail problems for the majority of patients,
      there are numerous other causes of nail dystrophies. This article aims to discuss
      some of the commoner causes of nail dystrophy. In addition it will give GPs an
      understanding of the anatomy and function of the nail and provide an approach to
      diagnosis based on morphology. Treatment will be dealt with in a subsequent
      article.

PMID- 9197055
TI  - I think I'm losing my hair.
AB  - As humans have evolved our hair has diminished to the point of being vestigial,
      yet it has assumed enormous psychological and social importance. For many, hair
      loss is synonymous with ageing, loss of attractiveness and desirability and has
      the potential to undermine self confidence and social interactions. Those
      affected are likely to seek out treatment, at any cost, both conventional and
      unconventional. The plethora of 'cures' for baldness and hair restoration clinics
      are testimony to the importance society places on a full head of hair and to the
      vulnerability of persons with hair loss.

PMID- 9197056
TI  - Could it be a drug eruption?
AB  - Drug eruptions can be a common reason for patients to present to the general
      practitioner. It has been estimated that as many as one in 40 visits to the GP
      may be related to adverse drug reactions. While many cutaneous drug reactions are
      readily recognisable, other potentially serious eruptions require the GP to have
      some knowledge of the varying clinical morphology of drug eruptions to make the
      diagnosis. It is also useful to be aware of certain groups of drugs that are
      associated with specific cutaneous reactions. In this article some of the typical
      patterns of drug reactions will be discussed, and some of the commoner causes
      listed. However, for many of these reaction patterns there are a huge number of
      possible drug causes, as well as other non drug causes that need to be
      considered.

PMID- 9197057
TI  - Practice compared. The UK and Australia.
AB  - OBJECTIVE: To compare the processes and cost of management of chronic health
      problems between a rural general practice in the UK and a similar practice in
      Australia. Patients were selected from three groups with either diabetes, asthma
      or depression. DESIGN: Case study, retrospective. This comparison was conducted
      during a 6 month practice exchange. SETTING: Wagin, Western Australia and Berwick
      upon Tweed, England. SUBJECTS: Ten people (five men, five women) were selected
      from each practice, for each disease type. Their records were culled and compared
      on the basis of how well they had satisfied the requirements of the protocols
      (where they existed) on the management of each disease. Other comparisons also
      included the number and cost of consultations, prescriptions and hospital stays.
      RESULTS: There was no apparent difference in the age/sex distributions of the
      populations studied. Comparisons of the three disease groups showed: Asthma
      results similar on most counts, except hospital admissions. Protocol uniformly
      poorly followed. Diabetes-results similar, except use/cost of prescription drugs
      which was much greater in Australia. The UK was much better following its
      protocol. Depression-Australia again used significantly more prescription drugs.
      The use and cost of GP/specialist visits was higher overall in Australia.
      CONCLUSION: This study suggests that a rural UK practice provides more cost
      effective review of chronic health problems. Further study would be warranted to
      investigate the impression that this was achieved at the expense of patient and
      doctor satisfaction.

PMID- 9197058
TI  - Self-determination in terminal care. A comparison of GP and community members'
      responses.
AB  - OBJECTIVES: To examine health practitioner and community concerns, priorities and
      preferred options regarding patient self-determination in terminal care. METHOD:
      A postal questionnaire was sent to 229 general practitioners in two areas of
      Queensland (Brisbane and Wide Bay) and to 1100 community members throughout
      Queensland. Questions covered a range of end of life decision making issues,
      including where people wish to die, the use of advance directives and proxy
      decision makers, and possible barriers to such options. RESULTS: GPs and
      community members held very different opinions on most issues: community members
      were divided between home, hospital and hospice as a preferred place to die,
      while GPs strongly favoured home as their preferred place to die. Both groups
      supported the use of advance directives and proxies, but differed significantly
      with respect to barriers preventing the use of such options. CONCLUSION:
      Clarifying differences in perceptions and preferred options between the two
      groups on end of life decision making should not only improve communication and
      interactions between GPs and their patients but also allow both groups to become
      full participants in current policy and practice debates on end of life
      decisions.

PMID- 9197059
TI  - Ross River virus infection. Diagnosis and treatment by general practitioners in
      South Australia.
AB  - OBJECTIVE: To determine the signs and symptoms used by general practitioners to
      diagnose Ross River virus (RRV) infection, to assess investigation and treatment
      patterns and to test differences between GPs, grouped by demographic
      characteristics. DESIGN AND SETTING: A postal questionnaire was sent to 264 GPs
      who had submitted serological specimens that proved to be positive for RRV to
      laboratories in Adelaide during the period October 1992 to August 1993. RESULTS:
      One hundred and seventy-four questionnaires were returned. Most had diagnosed
      between two and five cases of RRV infection (64.7%), although 20.7% of rural
      practitioners had diagnosed six or more cases. The symptom of 'pain in the
      joints' was ranked as the most important for suspecting RRV infection with joint
      effusion, rash and pyrexia ranked as important signs. Ninety-six per cent of GPs
      reported that they always performed RRV serology on patients with these symptoms.
      The most frequently cited treatments were rest (93.4%) and prescription of non
      steroidal anti inflammatory drugs (NSAIDS) (68.5%). There were no clinically
      significant differences between GPs, grouped by demographic characteristics, in
      their approach to the diagnosis or treatment of RRV infection. CONCLUSIONS: GPs
      in South Australia use similar groups of symptoms and signs to diagnose RRV
      infection. Most always used serology to confirm their clinical diagnosis and a
      large proportion performed blood tests that could establish alternative
      diagnoses.

PMID- 9197060
TI  - Depression in general practice.
AB  - Depression is the most common, serious psychological disability presenting to
      general practitioners. Its prevalence varies from 0.6 to 36% of GP encounters
      depending on the method of diagnosis. Apart from methodological differences, some
      of this variability relates to barriers in the diagnostic process. These include
      'doctor barriers' both personal and professional, 'consultation barriers', and
      real or perceived 'patient barriers'. Education and training of GPs to recognise
      and manage depression in all its guises is only one way of overcoming these
      barriers. Other ways include raising community awareness through public health
      campaigns and raising patient and doctor awareness by screening for depression in
      the course of seemingly unrelated consultations in 'at risk patients'. As 95% of
      depression is capable of being managed in general practice, GPs will need to be
      more active in this field to reduce the considerable burden of morbidity and
      mortality attributed to this condition.

PMID- 9197062
TI  - Practice tip. Looking for a liver edge or spleen.

PMID- 9197061
TI  - Never discount an animal vector.

PMID- 9197063
TI  - Vanishing point.

PMID- 9197064
TI  - Breast self examination.

PMID- 9197065
TI  - Why do(n't) aboriginal women have Pap smears?

PMID- 9197066
TI  - Obesity/overweight audit.

PMID- 9197067
TI  - The Fielding H. Garrison Lecture. "Bedside manners in the Middle Ages".

PMID- 9197069
TI  - Poliomyelitis and the neurologists: the view from England, 1896-1966.

PMID- 9197068
TI  - Gentlemanly versus scientific ideals: John Burdon Sanderson, medical education,
      and the failure of the Oxford School of Physiology.

PMID- 9197070
TI  - Recreating the body: women's physical education and the science of sex
      differences in America, 1900-1940.

PMID- 9197071
TI  - The Henry E. Sigerist Medieval Manuscript Reproduction Collection: a finding
      list.

PMID- 9197072
TI  - Graphical materials online.

PMID- 9197073
TI  - Penicillin-resistant Streptococcus pneumoniae in Ontario, 1987-1995.

PMID- 9197074
TI  - The abuse of cardiovascular procedures.

PMID- 9197075
TI  - Case report: bronchial atresia associated with pectus excavatum.

PMID- 9197077
TI  - Mentors of the past.

PMID- 9197078
TI  - The question of assisted suicide: why now?

PMID- 9197076
TI  - New generations of quinolones: with particular attention to levofloxacin.

PMID- 9197079
TI  - Physicians take collective responsibility for care.

PMID- 9197080
TI  - Who is minding the store?

PMID- 9197081
TI  - The changing female/male incidence of thyroid carcinoma in Connecticut.

PMID- 9197082
TI  - Implementation of the International Statistical Classification of Diseases and
      Related Health Problems, Tenth Revision (ICD-10).

PMID- 9197083
TI  - Cholera situation in the Americas, 1996.

PMID- 9197085
TI  - WHO/PAHO/UNESCO report. A consultation with experts on amoebiasis. Mexico City,
      Mexico 28-29 January, 1997.

PMID- 9197084
TI  - Situation of the blood banks in the region of the Americas, 1994-1995.

PMID- 9197086
TI  - Scientific Advisory Committee (SAC) meeting of the Caribbean Epidemiology Centre
      (CAREC)-1997.

PMID- 9197087
TI  - AIDS surveillance in the Americas.

PMID- 9197088
TI  - The effect of hearing impairment on the vocal characteristics of older people.
AB  - Measures of vocal intensity, frequency and harshness were compared for 19 hearing
      impaired and 21 normal-hearing people over 60 years of age. Significantly greater
      comfortable intensity levels were found in the hearing-impaired group, but the
      other measures of frequency and harshness were not significantly different. A
      large proportion of the subjects in both groups reported a history of gastro
      oesophageal reflux (GER), a condition associated with vocal fold pathology and
      hoarseness. Comparison of the GER and non-GER subjects on the measures of vocal
      function showed that the female GER speakers exhibited lower frequency on the
      vowel /u/ than the non-GER subjects. Clinicians need to be aware of the effect of
      highly prevalent disorders such as hearing impairment and GER on the voices of
      elderly speakers.

PMID- 9197089
TI  - A speaking task analysis of the dysarthria in cerebellar disease.
AB  - Cerebellar disease affects a number of skilled movements, including those in
      speech. Ataxic dysarthria, the speech disorder that typically accompanies
      cerebellar disease, was studied by acoustic methods. Control subjects and
      subjects with ataxic dysarthria were recorded while performing a number of
      speaking tasks, including sustained vowel phonation, syllable repetition,
      monosyllabic word production (intelligibility test), sentence recitation, and
      conversation. Acoustic data derived from the speech samples confirmed the
      hypothesis that temporal dysregulation is a primary component of the speech
      disorder. The data also show that the nature of the disorder varies with the
      speaking task. This result agrees with observations on other motor systems in
      subjects with cerebellar disease and may be evidence of a dissociation of
      impairments. Suggestions are offered on the selection of measures for a given
      task and on the role of the cerebellum in the regulation of speaking.

PMID- 9197090
TI  - Velopharyngeal function in association with artificial obstruction of the nose: a
      videonasendoscopic study.
AB  - Artificial obstruction of the nose can make the nasal cavity a cul-de-sac
      resonator, which has clearly audible consequences. The present study compares
      videonasendoscopic views of the velopharyngeal mechanism in test words uttered
      with the nose open and obstructed in 20 subjects with a Pierre Robin sequence and
      in 6 subjects without this sequence. A velopharyngeal flap was constructed on 12
      subjects. Videonasendoscopic findings were assessed by 3 judges with acceptable
      agreement. The results indicated that impairment of velopharyngeal function
      occurred significantly more often in subjects with a velopharyngeal flap. This
      was attributed to aerodynamic reasons. Clinical implications of the results are
      discussed.

PMID- 9197091
TI  - Developmental aspects of formant frequency and bandwidth in infants and toddlers.
AB  - Average formant frequency and formant bandwidth values are reported in a cross
      sectional sample of 20 children between 4 and 25 months of age. With the
      exception of a slight rise in F1 at 18 months of age, average F1 and F2 values
      changed little during the time period, while the average bandwidths for F1 (B1)
      and F2 (B2) were found to significantly decrease as age increased. The pattern
      observed for both average formant frequencies and formant bandwidths were
      attributed to developmental reconfiguration of the vocal tract.

PMID- 9197092
TI  - Three-dimensional phonetographic assessment of voice performance in professional
      and non-professional speakers.
AB  - For the assessment of voice performance, three-dimensional (3D) phonetograms were
      constructed using mean values of vocal pitch, vocal intensity, and phonation
      time. They were built up for groups of professional and non-professional male and
      female speakers. The 3D phonetograms of the professional and non-professional
      groups were projected into one another for the female as well as for the male
      speakers to facilitate comparison of the professional and non-professional
      groups. In addition, pitch-related cross-sections of the 3D phonetograms were
      created. These cross-sections plotted as sequences are useful to evaluate changes
      in vocal dynamics and phonation time in relation to the course of vocal pitch. In
      this contribution, it could be demonstrated that the 3D phonetograms of the non
      professional groups were completely enclosed by those of the professional groups
      who developed a greater vocal capacity. Furthermore, the cross-section sequences
      of the professional groups were obviously longer and broader than those of the
      non-professional groups. Details of group-specific differences with respect to
      the examined voice parameters are discussed.

PMID- 9197093
TI  - The use and misuse of N-of-one studies.

PMID- 9197094
TI  - The Frialit-2 implant system: five-year clinical experience in single-tooth and
      immediately postextraction applications.
AB  - In an observational study of 696 Frialit-2 implants in 376 patients that was
      carried out between 1990 and 1995, implants of varying diameters and lengths were
      delivered for a range of indications in the maxilla and mandible. Single-tooth
      replacement was performed in 42% of cases; of these, 22.4% were placed
      immediately following extraction. Study parameters (Plaque Index, Gingival Index,
      probing depth, Periotest value, and peri-implant bone loss) are reported in
      detail. Statistical analysis is based on a 97.6% rate of recall. The overall
      success rate was found to be 96% using the Kaplan-Meier statistical analysis. No
      difference was apparent between single-tooth applications and prosthesis
      restorations.

PMID- 9197096
TI  - Immediate loading of threaded implants at stage 1 surgery in edentulous arches:
      ten consecutive case reports with 1- to 5-year data.
AB  - Immediate loading of threaded implants with a fixed provisional restoration at
      stage 1 surgery was evaluated in 10 consecutive patients. The patients selected
      had to be completely edentulous and have adequate bone for a minimum of 10-mm
      long implants. A minimum of 10 implants were placed in each patient's arch. A
      minimum of five implants were submerged initially for medicolegal reasons and
      allowed to heal without loading. The remaining implants were loaded the day of
      stage 1 surgery. Once the provisional restoration was relined, it was cemented or
      screw retained. A total of 107 implants were placed in these 10 patients; 6 had
      them placed in the mandible, and 4 in the maxilla. Six patients were treated with
      Nobel Biocare implants, one with ITI Bonefit implants, two with Astra Tech
      TiOblast implants, and one with a 31 implant. Sixty-seven of 69 implants that
      were loaded integrated, and 37 of 38 submerged implants integrated. All 10
      patients have been restored with a definitive prosthesis, and all had a fixed
      provisional prosthesis from stage 1 surgery. The results of this study indicate
      that immediate loading of multiple implants rigidly splinted around a completely
      edentulous arch can be a viable treatment modality.

PMID- 9197095
TI  - Alveolar reconstruction with splitting osteotomy and microfixation of implants.
AB  - This report describes a surgical technique for reconstruction of the
      buccolingually reduced alveolar process. The technique involves the preparation
      of an artificial socket with immediate implant placement, which reduces total
      treatment time compared with two-stage procedures. Alveolar preparation comprises
      lamellar cortical splitting of the alveolus, interlamellar implant placement, and
      primary stabilization based on a microfixation technique. It was used for a wide
      range of indications involving single and multiple alveoli related to the
      partially dentate and the edentulous alveolar process. The results of 24
      Branemark standard implants and 97 ITI implants with 44 consecutively treated
      patients have been reviewed with a mean observation time of 34.3 months (range 6
      to 68 months). The main indicator for alveolar reconstruction was the narrow
      anterior maxillary arch. The 5-year cumulated success rate was 86.2%. Twelve
      implants failed during the observation period. The mean marginal bone loss was
      1.7 mm (range 0 to 7.5 mm). There was a low infection rate compared with membrane
      based GTR techniques. Treatment costs were low as a result of shorter treatment
      time.

PMID- 9197097
TI  - Vertical ridge augmentation using polylactic membranes in conjunction with
      immediate implants in periodontally compromised extraction sites: an experimental
      study in dogs.
AB  - Polylactic membranes were evaluated for vertical ridge augmentation around
      immediate implants in periodontally compromised extraction sites. Ligature
      induced periodontitis was produced in 10 adult beagle dogs. The periodontium was
      allowed to heal for 6 weeks. All premolar teeth were extracted and three implants
      were placed immediately into the extraction sockets on either side of the
      mandible so that the polished cone extended above the alveolar bone level. On one
      side of the mandible, the implants were covered with a 0.2-mm-thick polylactic
      membrane (DL-lactide-co-trimethylene carbonate in a ratio of 7:3). Histologic and
      morphometric analyses performed after 3 and 5 months revealed that the membrane
      group did not exhibit significantly greater bone-implant contact than the
      controls. The occurrence of dehiscences correlated significantly with use of the
      membrane. Use of the membrane was associated with significantly less peri-implant
      bone height after 5 months. No remnants of the membrane material could be
      identified after 3 or 5 months, indicating rapid resorption during the first
      weeks of implantation. The tested membrane material did not fulfill the
      requirements of resorption kinetics and space maintenance for guided bone
      regeneration in vertical ridge augmentation.

PMID- 9197098
TI  - Functional loads on freestanding and connected implants in three-unit mandibular
      prostheses opposing complete dentures: an in vivo study.
AB  - In vivo measurements of vertical forces and bending moments during biting and
      chewing were carried out on 10 three-unit prostheses in the posterior mandibles
      of five patients. Each patient had two prostheses, one supported by two implants
      and the other supported by one implant and one tooth. The results demonstrated no
      major difference in functional load magnitudes related to the support type. The
      distribution of load between the abutments was influenced more by the prosthesis
      geometry and implant placement than by the difference in load characteristics of
      tooth and implant. This conclusion, however, is limited to one implant connected
      to a tooth, because multiple implants form a considerably stiffer unit than do
      teeth. An increase in vertical load resulting from cantilever extensions on the
      prostheses was documented, both at bite fork measurements and during chewing. No
      substantial lateral bending was registered, probably because the flat occlusal
      surfaces and the presence of the opposing complete denture reduced lateral
      forces.

PMID- 9197099
TI  - Temperature rise during drilling through bone.
AB  - Temperature was measured during drilling in bovine cortical bone specimens. A
      surgical drill fitted with a custom-designed speedometer and mounted on a drill
      press was used to drill holes at one speed, 49,000 rpm, and at forces in the
      range of 1.5 to 9.0 N. The resulting temperatures were recorded by thermocouples
      placed at various locations. The distribution of maximum local temperature rise
      (delta T) was best fitted by the function delta T = aR-b, where R is the distance
      from the center of the drilled hole and a and b are constants that were found by
      regression analysis. It was also found that the temperature increased with force,
      up to about 4.0 N, and then decreased at forces greater than that because of
      decreased drilling time. A separate series of tests revealed that temperatures
      were higher in the longitudinal direction than in the circumferential direction;
      this difference was attributed to the anisotropic thermal properties of bone.

PMID- 9197100
TI  - Magnetic resonance imaging in patients with dental implants: a clinical report.
AB  - Magnetic resonance imaging is used more and more frequently as a diagnostic tool.
      Because high magnetic fields are used, knowledge on how these will affect
      implanted material and the patient is of great importance. Ferromagnetic
      properties of implant materials are seldom described by the manufacturer, but a
      doctor requesting magnetic resonance imaging of a patient must know about these
      properties. Not only is the composition of an alloy important, but also the size
      and shape of the metallic material as well as its position in the body. Implants
      from the Branemark System were tested; findings indicated that the implants were
      not influenced when exposed to magnetic resonance imaging. The artifacts caused
      by the implants were minor and did not jeopardize the evaluation of the scans.
      However, magnet keepers attached to the implants were found to cause major
      artifacts and must be removed before an implant patient is referred for a
      magnetic resonance imaging examination.

PMID- 9197101
TI  - Load factor control for implants in the posterior partially edentulous segment.
AB  - There are inherent biomechanical differences in the implant treatment of
      completely edentulous arches and posterior partially edentulous segments. The
      partial prosthesis does not benefit from cross-arch stabilization and is,
      therefore, more susceptible to bending loads. Because of the difference in
      mobility between teeth and implants, implants may carry a major share of load
      when mixed with teeth in the same quadrant. However, the frequency of implant
      overload in posterior partial restorations is low, and, with appropriate
      treatment planning, overload in these situations is almost always preventable. A
      checklist procedure is proposed to help the clinician enumerate and evaluate
      deleterious load factors. By screening patients for such factors in advance, the
      clinician may identify and avoid potential overload situations when conceiving
      and fabricating implant-supported posterior partial prostheses. A second
      checklist, for use at follow-up appointments, lists alarm factors that serve as
      an early warning of overload once the prosthesis is in place.

PMID- 9197103
TI  - Use of a surgical positioner for bone-anchored facial prostheses.
AB  - The use of osseointegrated implants to retain facial prostheses in craniofacial
      rehabilitation is a reliable procedure. Proper location of the implants is
      critical for fabrication of a prosthesis with ideal shape and contour. The use of
      a positioner at time of surgery can guide placement of the implants to achieve an
      optimum result. The positioner is also useful as a guide to the shape of the
      retentive element and as a quick method for obtaining a wax pattern for the
      prosthesis. This article describes-the fabrication and applications of a
      positioner.

PMID- 9197102
TI  - Tolerance measurements of various implant components.
AB  - Machining tolerance, an intrinsic characteristic that exists between machined
      implant components, identifies the amount of horizontal shift possible between
      paired components. Machining tolerances between implant components (abutment,
      gold, cylinder, impression coping, and brass abutment replicas) were measured
      with a coordinate measuring machine. The measured tolerances ranged from 22 to
      100 microns. Machining tolerances between implant components should be included
      in future studies of accuracy, because it is an inherent characteristic of the
      component itself.

PMID- 9197104
TI  - The relationship of some histologic parameters, radiographic evaluations, and
      Periotest measurements of oral implants: an experimental animal study.
AB  - The objective of this study was to analyze the efficacy and correlation between
      clinical and histologic parameters used to evaluate oral implants. After
      extraction of the premolars and a healing time of 4 months in 16 Dutch goats,
      four Branemark implants were placed in the maxillary left and right premolar
      regions. After a healing time of 6 months, followed by another 4 months with the
      permucosal abutments, the goats were sacrificed and the jaws were block-resected.
      Before histologic preparation, long-cone radiographs were made and Periotest
      scores of the implants were recorded. Bone level measured histomorphometrically
      were found to be 0.85 mm more apically, compared to that measured radiologically
      (P = .001). Furthermore, statistically significant correlations (P > 0.2) were
      not found between the Periotest values of the calcium-phosphate-coated and
      uncoated implants for (1) the first thread in contact with bone, or (2) with the
      total number of threads in contact with bone. It was concluded that the
      radiologic data overscored the real marginal bone level around screw-shaped oral
      implants, and that the Periotest device is neither able to discriminate between
      the first thread nor between the total number of threads in contact with bone.

PMID- 9197105
TI  - Dissolution of stainless steel in artificial saliva.
AB  - Dissolution of stainless steel type 304 in artificial saliva was studied by
      electrochemical methods, electron spectroscopy for chemical analysis, and atom
      absorption spectroscopy. The samples were polarized in the -400 mV (saturated
      calomel electrode) to -50 mV (saturated calomel electrode) range. The total
      thickness of the passive film was found to be 25 +/- 3 A, independent of the
      potential. The passive film consists of a duplex structure: an inner layer of
      (Cr0.5Fe0.5)2O3 and an outer layer of a mixture of Cr(OH)3 and (CrxFey)PO4.2H2O.
      The analysis indicated that 11 micrograms/cm2 of the alloying elements were
      dissolved during exposure for 1 year.

PMID- 9197106
TI  - Detection times of natural teeth and endosseous implants revealed by the method
      of reaction time.
AB  - Reaction times were employed to assess whether implants have longer detection
      times than natural teeth. A soft push was applied to an endosseous implant or to
      the corresponding natural tooth. Patients were asked for a speeded manual
      response upon the detection of the push. The temporal interval from the onset of
      the push to the onset of the manual response denoted the reaction time. This
      measure was only slightly longer for endosseous implants than for natural teeth,
      indicating that an implant's ability to detect rapid load changes is almost
      unimpaired.

PMID- 9197108
TI  - Medicaid issues.

PMID- 9197109
TI  - Intraosseous infusion performed in the prehospital setting: South Carolina's six
      year experience.
AB  - Our data do not demonstrate that a prehospital intraosseous infusion protocol
      will improve the outcome of prehospital pediatric patients with cardiac arrest.
      The number of patients in our study is too small to allow us to draw a conclusion
      as to the effect of intraosseous infusion on altering survivability of pediatric
      cardiac arrest in the prehospital setting. More study is necessary to determine
      whether there might be a group of pediatric patients with cardiac arrest or
      hypovolemic shock who could potentially benefit in a prehospital setting from
      this procedure.

PMID- 9197107
TI  - A new animal model for maxillary sinus floor augmentation: evaluation parameters.
AB  - This study describes a novel animal model of the maxillary sinus floor
      augmentation procedure used to assess bone formation during 12 weeks in response
      to a recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen
      sponge (ACS) sinus implant. A buffer-ACS implant was used as a control. Animal
      response was monitored using computerized tomography and physical, hematologic,
      gross pathologic, and histologic evaluations. The rhBMP-2/ACS implants maintained
      a relatively constant size postsurgery and showed a time-dependent increase in
      mineralization. The buffer/ACS control implants failed to mineralize and were
      resorbed by 4 weeks. The model served effectively and without complication.
      Results indicate rhBMP-2/ACS implants deserve consideration as alternatives to
      traditional grafting procedures.

PMID- 9197111
TI  - Eleanora Bennette Saunders: a pioneering psychiatrist.

PMID- 9197110
TI  - Cardiac constipation.

PMID- 9197112
TI  - Of Hegel and health care financing.

PMID- 9197113
TI  - Leonidas Michael Stokes, M.D., 1879-1945.

PMID- 9197114
TI  - "Swapping grief": the role of the laity in alternative medical encounters.

PMID- 9197115
TI  - Framing animal disease: housecats with feline urological syndrome, their owners,
      and their doctors.

PMID- 9197116
TI  - American physicians and sex research and expertise, 1900-1990.

PMID- 9197117
TI  - Longitudinal study of deinstitutionalization and the exercise of choice.
AB  - Day-to-day choices available to former institution residents with severe/profound
      developmental disabilities (movers) were assessed before and after
      deinstitutionalization and compared with peers who remained in the same
      institutions (stayers). Data were gathered annually for both groups for 3 years
      after baseline. Personal characteristics of the two groups did not differ
      significantly at baseline, except that stayers exhibited more challenging
      behavior. This was controlled by using baseline challenging behavior as a
      covariate in group comparisons. Overall, movers exercised significantly more
      choice, although groups did not differ at baseline. Effects of
      deinstitutionalization did not differ with level of disability. However, the
      absolute level of choice available to both movers and stayers was very low.

PMID- 9197118
TI  - A PASS 3 evaluation of community residences in Wales.
AB  - PASS 3 was used to evaluate 14 residential services for people with mental
      retardation. Residents had a broad range of abilities. Size of residences ranged
      from one to seven residents. PASS scores were generally associated with both
      resident's ability level and smaller size of living unit. Overall, the residences
      were shown to be well-located and reasonably home-like. However, residence
      personnel tended to lack organized means and competencies to promote resident
      development and experience. Administrative practices were also weak. Attention
      must be given to factors other than residence size, location, building
      characteristics, and staffing parameters when services are commissioned and when
      service contracts are specified and reviewed.

PMID- 9197119
TI  - Nutrition knowledge and obesity of adults in community residences.
AB  - Variation in nutrition knowledge of adults with mild or moderate mental
      retardation (30 obese, 27 nonobese) from four community agencies was examined as
      a function of their body mass and level of mental retardation. They completed a
      nutrition knowledge test adapted for individuals with mental retardation.
      Multiple regression analyses revealed significant effects of level of mental
      retardation and body mass on nutrition knowledge. Adults with mild mental
      retardation possessed greater nutrition knowledge than did those with moderate
      mental retardation, and obese individuals possessed more knowledge than did
      nonobese individuals. The unexpected relation between nutrition knowledge and
      degree of obesity implies an influential role for environmental factors in the
      development of obesity.

PMID- 9197120
TI  - Analysis of the typicalness of supported employment jobs, natural supports, and
      wage and integration outcomes.
AB  - Natural support has become a well-recognized concept to both practitioners and
      federal regulators. Although qualitative and descriptive information about
      natural supports is available, there is no commonly accepted definition and
      little quantitative documentation. Nonetheless, the notion of "natural supports"
      remains a potentially viable strategy toward improving supported employment
      outcomes. In this study the relation between employment features and outcomes for
      employees with disabilities in relation to natural support was investigated as
      was the extent to which the experiences of people with disabilities mirror
      typical employment conditions experienced by people without disabilities.

PMID- 9197121
TI  - A practical strategy to increase participation and reduce challenging behavior
      during leisure skills programming.
AB  - The effects of prompting, reinforcer sampling, and assistance on participation
      and challenging behavior of two adults with severe disabilities were examined
      under three conditions during a leisure program. For baseline, leisure materials
      were absent, but there was opportunity for social interaction. Next, leisure
      materials were provided, but participants were neither prompted nor assisted to
      use these materials. During intervention, participants sampled the materials and
      were assisted to use each item during a 5-minute prompting sequence. A reversal
      design demonstrated that the prompting sequence was associated with increased
      participation and reduced challenging behavior. These improvements were
      maintained as the frequency of the prompting sequence was reduced from four times
      to once per session.

PMID- 9197123
TI  - Effect of social and educational policies on the number of persons with mild
      mental retardation in Sweden.

PMID- 9197122
TI  - Framework for analyzing health care models serving adults with mental retardation
      and other developmental disabilities.
AB  - A conceptual framework was presented for describing, comparing, and analyzing the
      structure of health care models serving adults with mental
      retardation/developmental disabilities (MR/DD). This framework, which was drawn
      from Donabedian's (1980) work on the components of quality of health care
      structure, process, and outcome-provides a basis for comparing health service
      models according to three key domains: measures of access, comprehensiveness, and
      cost. We used this framework to describe three existing programs that use
      different models to serve this population.

PMID- 9197124
TI  - Systematic distortion of statistics as a result of racism and its effect on the
      human services system.

PMID- 9197125
TI  - Patience, trust build strong coalitions. Physicians help to establish healthy
      communities.

PMID- 9197126
TI  - IMGs set goals for AMA section.
AB  - International medical graduates have become an important part of the American
      health care structure in recent decades, but too often they remain second-class
      citizens within the medical community. Increasingly, voices within medicine have
      called for formal recognition of the unique needs of IMG physicians.

PMID- 9197127
TI  - State announces Medicaid awards. Capitation transition moves at a dizzying pace.

PMID- 9197128
TI  - Low payments jeopardize care. Medicaid reimbursement affects doctors and
      patients.

PMID- 9197129
TI  - Pregnancy and iron deficiency: unresolved issues.
AB  - Iron deficiency and iron deficiency anemia are prevalent among pregnant women.
      The extent to which iron deficiency affects maternal and neonatal health is
      uncertain. Existing data suggest that maternal iron deficiency anemia may be
      associated with adverse outcomes, including preterm delivery and higher maternal
      mortality. Further research is needed on the maternal and neonatal benefits of
      iron supplementation during pregnancy.

PMID- 9197130
TI  - Interaction of iron with other nutrients.
AB  - Iron is essential for oxygen transport, oxidative metabolism, and cellular
      growth. Interactions between iron and other dietary factors play a significant
      role in determining the adequacy of iron nutrition and have important
      implications for food fortification in developing countries. Vitamin A and
      vitamin C deficiency states may affect iron transport, metabolism, and storage
      within the body.

PMID- 9197131
TI  - Iron, anemia, and infection.
AB  - The data on the relationship between iron deficiency and infection are
      conflicting. Some researchers conclude that mild iron deficiency is beneficial
      for immunity, whereas others contend that any deficit is not good for immunity.
      Additionally, infection or inflammation generate anemia and profound changes in
      iron metabolism mediated by cytokines. These changes are important confounders to
      consider in assessments of iron status.

PMID- 9197132
TI  - Psychomotor development and behavior in iron-deficient anemic infants.
AB  - Research has shown an association between iron deficiency anemia and adverse
      effects on behavior and psychomotor development in infants and children. The
      exact mechanisms behind these associations are not fully understood. Additional
      research is necessary.

PMID- 9197133
TI  - Iron deficiency and educational deficiency.
AB  - Existing data suggest that iron deficiency anemia (IDA) is a risk factor for poor
      educational performance in schoolchildren. The synergistic effect of IDA in
      combination with other forms of malnutrition and other risk factors may affect
      educational performance more strongly. Thus, IDA and its effect on educational
      performance should be studied in the context of other risk factors.

PMID- 9197134
TI  - Daily versus weekly iron: we still might not be asking the right questions.

PMID- 9197135
TI  - A medical school honor code: what does it mean?

PMID- 9197136
TI  - Caring for the patient: a troubling paradox.

PMID- 9197137
TI  - Apathy, empathy, physicians, and Chekhov.
AB  - Healing depends on a caring, involved physician. In his story "Ward Number Six,"
      Anton Chekhov illustrated how patients suffer when physicians become apathetic.
      Reading this story may inspire physicians to resist apathy and assume greater
      responsibility for the social conditions that impact on their patients' well
      being. It may also stimulate physicians' imagination in such a way as to improve
      their ability to empathize with their patients. Finally, the act of reading
      itself--particularly reading great literature such as "Ward Number Six," can help
      rejuvenate those physicians who struggle with their own apathy.

PMID- 9197138
TI  - Medicine and poetry: a pathway of communication.

PMID- 9197139
TI  - The last physician? "The parable of the last physician".

PMID- 9197140
TI  - The other shoe with E-care: cardiac experiences fifteen years apart.

PMID- 9197141
TI  - "Felix Randal": a poem about medicine.

PMID- 9197142
TI  - Dying in America.

PMID- 9197143
TI  - Quo vadis medicina?

PMID- 9197144
TI  - A woman physician-patient: her view of Wilson's disease.

PMID- 9197145
TI  - Avenues for child advocacy.

PMID- 9197146
TI  - Altruism--a flawed morality?

PMID- 9197148
TI  - [Uncontrolled hypertension after Cushing's syndrome].

PMID- 9197147
TI  - [Papulo-nodular skin lesions associated with monoclonal IgA gammapathy].

PMID- 9197149
TI  - [Neurotoxicity of acyclovir].

PMID- 9197150
TI  - Fine-needle aspiration cytology in infectious disease.

PMID- 9197151
TI  - Epidemiological aspects of the Brazilian spotted fever: seasonal activity of
      ticks collected in an endemic area in Sao Paulo, Brazil.
AB  - Ticks were collected from vegetation and animals at monthly intervals during one
      year (1993-1994) in an endemic area of Brazilian spotted fever in the Country of
      Pedreira, State of Sao Paulo. Six species of ticks were identified Amblyomma
      cajennense, Amblyomma cooperi, Amblyomma triste, Anocentor nitens, Rhipicephalus
      sanguineus and Boophilus microplus. Only the first species was sufficiently
      numerous to permit a quantitative study with seasonal activity, although the
      distribution and source of capture of other species were observed and are
      reported. This information is correlated with the epidemiology of tick-borne
      rickettsiosis.

PMID- 9197152
TI  - Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease
      patients: I--Behavioral characterization in vitro.
AB  - In this study, we isolated Trypanosoma cruzi from chronic Chagas heart disease
      and from megaesophagus patients. The parasite stock hSLU239 (heart disease)
      yielded clones h1 and h2, whereas stock mSEU142 (megaesophagus) yielded clones
      m1, m2, m3 and m4. The parasite growth kinetics, doubling time and
      differentiation in axenic liquid medium showed broad behavioral diversity. It was
      shown that a particular pattern of behavior for a parental stock could not
      necessarily be assigned for subsequent clones. This study indicates that i) each
      Chagas disease patient is infected with several T. cruzi populations; ii) clonal
      lines derived from patient samples may have different biological characteristics
      from the original isolate; and that iii) additional behavioral and/or molecular
      markers are required for further characterization of Trypanosoma cruzi stocks and
      clones derived from Chagas disease patients in order to identify correlations
      with pathology.

PMID- 9197158
TI  - The perceptual aspect of nursing art: sources of accord and discord.
AB  - Many authors have argued that nursing art involves a perceptual aspect.
      Perception is said to allow the artfull nurse to see, or envision, possibilities
      and to apprehend meaning in patient encounters. Although many nurses appear to
      agree that nursing art involves a perceptual ability, there is no apparent
      agreement about the nature of that ability. Indeed, a philosophical analysis
      revealed that sources of discord about the perceptual aspect of nursing art
      center on questions regarding the focus of the perceptual ability, the purpose of
      nursing art, whether foreknowledge is required, and whether the artfull nurse's
      perceptions are verifiable. The debate regarding the perceptual aspect of nursing
      art has been constructed with the hope that it will foster further debate and
      analysis about nursing art. Ultimately, the resolution of the sources of discord
      will assist in decisions about how the art of nursing is best pursued and
      developed.

PMID- 9197153
TI  - Chagas' disease: an algorithm for donor screening and positive donor counseling.
AB  - Classical serological screening assays for Chagas' disease are time consuming and
      subjective. The objective of the present work is to evaluate the enzyme immuno
      assay (ELISA) methodology and to propose an algorithm for blood banks to be
      applied to Chagas' disease. Seven thousand, nine hundred and ninety nine blood
      donor samples were screened by both reverse passive hemagglutination (RPHA) and
      indirect immunofluorescence assay (IFA). Samples reactive on RPHA and/or IFA were
      submitted to supplementary RPHA, IFA and complement fixation (CFA) tests. This
      strategy allowed us to create a panel of 60 samples to evaluate the ELISA
      methodology from 3 different manufacturers. The sensitivity of the screening by
      IFA and the 3 different ELISA's was 100%. The specificity was better on ELISA
      methodology. For Chagas disease, ELISA seems to be the best test for blood donor
      screening, because it showed high sensitivity and specificity, it is not
      subjective and can be automated. Therefore, it was possible to propose an
      algorithm to screen samples and confirm donor results at the blood bank.

PMID- 9197159
TI  - A transactional perspective on critical thinking.
AB  - The quality of thinking has received much attention within the last decade. The
      scientific inquiry models introduced by Dewey, Dressel and Mayhew, and Watson
      Glaser have been expanded to incorporate such aspects as reflection, development,
      attitude, skill, and knowledge domain. Dichotomies between critical and creative
      thinking have been eased. While this scholarship on thinking has been impressive,
      current pedagogy remains focused on scientific inquiry and on received knowledge.
      In nursing the learning paradigm has been similarly focused for the past 3
      decades on a scientific inquiry model and received knowledge. The major cognitive
      approach to education and practice has been the nursing process, a linear problem
      solving paradigm equivalent to the scientific method. This linear approach does
      not fully account for how nurses think and make judgments in clinical practice.
      The Transactional Model of Critical Thinking presented in this paper addresses
      the complexity of critical thinking in nursing. The model provides an educative
      and novel vision of thinking based on a transactional view of the individual,
      personal attributes, and the environment. Components and elements of the model
      are described and suggestions made for teaching-learning and for evaluation of
      critical thinking in nursing.

PMID- 9197160
TI  - Chronic sorrow in persons with Parkinson's and their spouses.
AB  - Chronic sorrow is the grief experienced from continual loss during the trajectory
      of an illness or disability. The presence and nature of chronic sorrow were
      determined in a sample of six persons with Parkinson's disease and four of their
      spouse caregivers using the Burke NCRCS Questionnaire. Four of the afflicted
      individuals and two of the spouse caregivers reported symptoms of chronic sorrow
      that for half of them were more intense than at the time of diagnosis.
      Respondents used extensive problem-solving and emotive coping strategies to
      handle their sorrow. Most of the respondents described themselves within the
      context of the illness and the care required. Losses triggering their sorrow
      included loss of future plans, restricted social life, and inability to travel
      and participate in hobbies. Support from others was restricted mainly to
      physicians at the time of diagnosis and close family. Supportive nursing
      interventions for their grief are indicated.

PMID- 9197161
TI  - Predicting unpredictability: a model of women's processes of predicting battering
      men's violence.
AB  - This paper proposes a theoretical model of how women predict men's violence
      within the context of battering. The model was developed from a grounded theory
      study of 30 women. Participants were recruited using advertisements in free
      neighborhood newspapers. Interviews were conducted in small groups or
      individually. The analysis revealed that battered women developed sophisticated
      knowledge about and response patterns to their partners' violent behaviors. They
      identified specific changes in their partners' eyes, speech, and tone of voice
      and described specific situations that served as warning signs of potential
      violence. Once able to identify warning signs, women responded with strategies of
      avoidance, engagement, fleeing, and enlisting the help of others to avert or
      delay violent incidences. These strategies provided temporary relief but did not
      usually result in the cessation of violence.

PMID- 9197162
TI  - Hepatitis G virus.

PMID- 9197163
TI  - Management of autoimmune hepatitis.
AB  - AIH is an organ-specific autoimmune disease with a variable course. It is
      important to distinguish AIH from other liver diseases. Early diagnosis with
      appropriate management improves the quality of life as well as survival rate.

PMID- 9197164
TI  - Abdominal imaging in the diagnosis of portal hypertension.

PMID- 9197165
TI  - Prophylaxis of hepatitis B virus infection following a needle stick exposure.

PMID- 9197166
TI  - Discriminant analysis of biochemical parameters in liver disease.
AB  - Discriminant function analysis has been used to investigate the relative value of
      six biochemical parameters (plasma ferritin, C-reactive-protein, bilirubin,
      alkaline phosphatase, glutamic oxaloacetic acid transaminase and albumin) in the
      diagnosis of liver disease. This was done among four groups totalling 70 subjects
      including healthy controls and patients with acute viral hepatitis, liver
      cirrhosis and primary hepatocellular carcinoma. Albumin had most value in
      distinguishing between groups, followed cumulatively by ferritin, alkaline
      phosphatase, C-reactive protein, bilirubin and glutamic oxaloacetic acid
      transaminase. However, if data on albumin, alkaline phosphatase, bilirubin and
      glutamic oxaloacetic acid transaminase had already been routinely collected,
      there would be no advantage in collecting data on ferritin and C-reactive
      protein. Any four of the six parameters would be of about equal value in
      distinguishing between diagnostic groups. When the data on all six biochemical
      parameters was combined in an optimum way, about 66% of all individuals could be
      correctly assigned to one of the four groups using biochemical markers alone.
      While the control subjects and patients with acute viral hepatitis formed a
      relatively well defined, tight cluster (apart from two patients with acute viral
      hepatitis), patients with liver cirrhosis and primary hepatocellular carcinoma
      were almost indistinguishable, using these biochemical parameters. If the latter
      two groups were pooled, then about 86% of subjects could be correctly classified.

PMID- 9197167
TI  - Needle aspiration in large amoebic liver abscess.
AB  - The role of percutaneous needle aspiration for therapy of uncomplicated, large
      amoebic liver abscess (ALA) is not defined. Twenty nine patients of ALA with a
      cavity larger than 5 cm were randomised to two groups: (i) metronidazole 800 mg
      tid for 10 days combined with needle aspiration (group A, n = 15) and (ii)
      metronidazole therapy alone (group B, n = 14). Clinical parameters, viz, fever,
      pain and abdominal tenderness were recorded daily and graded 0 to 3 (in order of
      increasing severity). A statistically significant benefit was demonstrated in
      group A for clinical parameters evaluated. Group A patients took less time to
      become afebrile from the grade 2 level as compared to group B (3.8 +/- 1.7 days
      and 5.6 +/- 2.2 days respectively; p < 0.05). Reduction in pain intensity and
      abdominal tenderness from grade 2 to 1 also occurred earlier in group A (0.7 +/-
      0.7 days vs 2.9 +/- 0.9 days for pain, P < 0.001 and 1.7 +/- 0.8 days vs 2.9 +/-
      1.2 days for abdominal tenderness, p < 0.001). The mean duration of
      hospitalization was significantly shorter in group A as compared to group B (5.8
      +/- 0.8 days vs 7.4 +/- 1.5 days, p < 0.001). Improvement in haematological and
      biochemical variables was similar in both groups. We conclude that percutaneous
      therapeutic needle aspiration of uncomplicated, large ALA hastens clinical
      recovery.

PMID- 9197168
TI  - Histological spectrum of lymphoid follicles and aggregates in Helicobacter pylori
      gastritis.
AB  - Seventy three patients of non ulcer dyspepsia underwent upper gastrointestinal
      endoscopy with biopsy from antrum and body of stomach. The tissue was stained
      with hematoxylin eosin and warthin starry stain. The severity of gastritis was
      correlated with the presence of Helicobacter pylori and lymphoid follicles and
      aggregates. The incidence of chronic atrophic gastritis and Helicobacter pylori
      were found to be 97% and 64.1% respectively. Lymphoid follicles and aggregates
      were seen in 32.9% of chronic atrophic gastritis. Severity of gastritis with
      activity correlates with Helicobacter pylori colonisation and the presence of
      lymphoid follicles and aggregates. We have found that there is no difference
      between presence of lymphoid follicles and aggregates in Helicobacter pylori
      positive and negative gastritis. The development of lymphoid follicles probably
      represents an immune response to the colonisation of gastric mucosa by
      Helicobacter pylori.

PMID- 9197169
TI  - Primary small intestinal adenocarcinoma.
AB  - Seven patients with adeno-carcinoma of the small intestine were seen over a
      period of five years. Four were localized to the duodenum, the jejunum was
      involved in two and the ileum in one. Abdominal pain, weight loss, anemia and
      obstruction were the most common presenting complaints. Endoscopy was the primary
      diagnostic modality for the duodenal tumours. Diagnostic accuracy of barium
      contrast examination was 83%. Curative resections were performed in two patients
      and palliative surgery in the rest.

PMID- 9197170
TI  - A case of steroid refractory ulcerative colitis treated with cyclosporin.

PMID- 9197171
TI  - Nucleolar organiser regions in different colonic epithelia.
AB  - The argyrophilic technique (AgNOR) was applied to paraffin sections of 10 acute
      self-limited colitis, 15 ulcerative colitis (UC), 5 ulcerative colitis with
      indefinite dysplastic change, 10 adenomatous polyps, 20 colorectal
      adenocarcinomas and 10 normal colorectal mucosa. The mean number of nucleolar
      organiser regions (NORs) per nucleus ranged between 1.62-2.00 (95% CI 1.77-1.93)
      for normal colon, 2.47-3.80 (95% CI 2.71-3.21) for acute colitis, 1.66-2.75 (95%
      CI 2.13-2.44) for UC, 3.60-4.00 (95% CI 3.67-3.94) for UC with indefinite
      dysplasia, 3.00-4.04 (95% CI 3.41-3.81) for adenomatous polyps and 3.59-6.70 (95%
      CI 4.04-4.72) for colorectal adenocarcinoma. The differences observed were
      statistically significant. There was a significant difference of AgNOR counts
      between adenomatous polyp and UC with indefinite dysplasia in comparison to those
      observed in regenerative epithelium of acute colitis and UC without dysplasia.
      Hence the technique may be used as an adjunct to routine histology for
      delineating dysplastic changes in colonic epithelium.

PMID- 9197172
TI  - Cysto-bilio-bronchial communication in a hydatid cyst of liver.

PMID- 9197173
TI  - Carcinoma gallbladder: atypical presentations and unusual associations.
AB  - Patients with carcinoma of the gall bladder (CaGB) may have atypical
      presentations and unusual associations. Out of 324 patients with CaGB seen at a
      tertiary referral center in northern India, 26 (8%) had atypical clinical
      presentations and 34 (10%) had unusual associations. The atypical presentations
      were empyema (5), acute cholecystitis (3), post-cholecystectomy benign biliary
      stricture (3), carcinoma of the head of pancreas (3), gastric outlet obstructions
      (2) and liver abscess (1). Unusual associations were common bile duct stones
      (18), left supraclavicular lymph node metastasis (11), Mirizzi's syndrome (3),
      inguinal lymph node metastasis (1) and umbilical metastasis (1). Majority of
      these patients had advanced disease and curative resection was not possible; a
      worthwhile palliation was however possible in the majority.

PMID- 9197174
TI  - Short segment oesophago-cardiomyotomy for achalasia cardia.
AB  - Over a seven year period, 25 patients of achalasia cardia underwent a
      transabdominal short segment oesophago-cardiomyotomy. There was no operative
      mortality. Two patients had a mucosal tear, detected intraoperatively and
      promptly repaired. All patients were regularly followed up (range 1 to 7 years).
      Clinical results were excellent in 76%, good in 20% and fair in 4%. No patient
      developed reflux or required reoperation for residual dysphagia. We conclude that
      a transabdominal short segment oesophago-cardiomyotomy performed carefully is a
      safe and effective procedure in the treatment of achalasia.

PMID- 9197175
TI  - A case of appendicular diverticulitis leading to mucocele of the appendix.

PMID- 9197176
TI  - Cell cycle checkpoints and apoptosis: potential for improving radiation therapy.

PMID- 9197178
TI  - The role of the IGF-I receptor in apoptosis.

PMID- 9197177
TI  - Structure and function of interleukin-1 beta converting enzyme.
AB  - An overwhelming body of evidence has shown that IL-1 beta is a major mediator of
      inflammatory disease (Tocci and Schmidt, 1996). The discovery of ICE, a unique
      processing enzyme involved in the production of active IL-1 beta, has provided a
      new approach to specifically block the production of this potent cytokine.
      Consequently, the discovery and development of inhibitors against the enzyme
      could hold great promise therapeutically. Potent inhibitors of the enzyme would
      be useful in the treatment of a number of important inflammatory diseases and
      potentially in the management of leukemia (Arend, 1993b; Estrov and Talpaz,
      1996). A number of key questions must be answered before the therapeutic
      potential of such inhibitors can be realized. The development of a
      pharmaceutically acceptable cysteine proteinase inhibitor will almost certainly
      involve new chemical strategies gauged at safely inactivating the enzyme. For
      such inhibitors, it will be necessary to achieve selectivity for ICE from among
      the growing number of ICE family members while retaining potency. It will also be
      important to establish the level of inhibition of IL-1 beta required to achieve
      therapeutic efficacy. The studies comparing IL-1 beta- and ICE-deficient mice
      suggest that complete abrogation of IL-1 beta is required to achieve efficacy in
      models of inflammation. It is not known if this is the case in humans.
      Understanding the source of the residual IL-1 beta produced in ICE-deficient mice
      will be important in order to ascertain if a similar mechanism could generate
      active IL-1 beta in patients receiving if a ICE inhibitor. As for ICE itself, a
      number of formidable questions remain regarding its regulation and mechanism of
      activation. Answering these questions experimentally will present a major
      challenge due to the extremely low levels of enzyme present in cells. Studies on
      other family members may provide easier access to some of these questions and
      provide clues that can be applied to ICE. The components of the pathway involved
      in IL-1 trafficking and secretion are unknown, as are the mechanisms of ICE
      activation and regulation. Clearly other cellular proteins that have yet to be
      discovered will be involved in each of these processes, opening up new avenues of
      research in this field.

PMID- 9197179
TI  - Bcl-2 family proteins and the hormonal control of cell life and death in normalcy
      and neoplasia.

PMID- 9197181
TI  - Viral inhibitors of apoptosis.

PMID- 9197180
TI  - Pathways of p53-dependent apoptosis.

PMID- 9197182
TI  - Global case-detection trend in leprosy.

PMID- 9197183
TI  - Physicians and psychologists beware: have you examined your patient today?

PMID- 9197184
TI  - Ontario's health care: a pox on doctors and patients.

PMID- 9197185
TI  - Death in Monroe County in 1853.

PMID- 9197186
TI  - Diffuse malignant pleural mesotheslioma at CAMC: a retrospective study of 50
      patients.
AB  - The cases of 50 patients who were treated for pleural diffuse malignant
      mesothelioma at Charleston Area Medical Center from 1966-1992 were reviewed
      retrospectively. Diagnosis was most often made by thoracoscopy or exploratory
      thoracotomy; pleural cytology was rarely contributory. The delay in diagnosis was
      often long (median time, 2.5 months; range 1-12 months). The median survival was
      only 6 months. Six clinical variables were analyzed for prognostic significance.
      Multivariate analysis showed that stage of disease, age, histology, and smoking
      history were the most important prognostic factors. Previous asbestos exposure
      was found in 74% of the patients. There was no cure of mesothelioma, and we did
      not find any significant differences in survival among groups of patients
      subjected to the different therapeutic measures. If new active therapies are
      identified, it would be useful to compare them to a best supportive care arm in
      order to demonstrate the value of any new therapeutic approach.

PMID- 9197187
TI  - Malignant carcinoid tumor and synchronous malignant extraadrenal paraganglioloma.
AB  - Gastrointestinal carcinoid tumor is often considered the most common
      neuroendocrine tumor of the small intestine. The overall incidence of 1% in the
      general population is quite low. Extraadrenal paragangliomas are rarer still, and
      the incidence of both of these tumors in the malignant state is exceedingly rare.
      This article describes the case of a patient who had both a malignant carcinoid
      tumor as well as a malignant retroperitoneal paraganglioma occurring
      synchronously. A review of the literature concerning these tumors is also
      presented.

PMID- 9197188
TI  - The use of radiofrequency catheter ablation to cure dilated cardiomyopathy.
AB  - Incessant supraventricular tachycardia can cause a dilated cardiomyopathy. This
      article discusses the case of a 55-year-old woman whose cardiomyopathy was
      reversed when she underwent successful radiofrequency catheter ablation of a
      unifocal atrial tachycardia.

PMID- 9197190
TI  - Month devoted to awareness of Tourette syndrome.

PMID- 9197189
TI  - Co-existing endometrial adenocarcinoma and tubal ectopic pregnancy: a case
      report.
AB  - Adenocarcinoma of the endometrium co-existing with pregnancy is a rare event.
      Twelve such cases have been reported in patients with intrauterine pregnancies.
      Co-existence with tubal ectopic pregnancy is even more uncommon. Only one such
      patient with tubal ectopic pregnancy was found in the literature; the pathologic
      findings were not, however, illustrated. We report on a very rare event, co
      existing adenocarcinoma of the endometrium and ectopic tubal pregnancy, with
      illustration of the pathologic finding.

PMID- 9197191
TI  - Mid-level practitioners help physicians meet growing medical needs.

PMID- 9197193
TI  - Nurse practitioners: the American experience.

PMID- 9197192
TI  - Physician assistants (PAs) provide quality care.

PMID- 9197194
TI  - Clinical nurse specialists.

PMID- 9197195
TI  - Guidelines for the utilization of unlicensed assistive nursing personnel.
      Wisconsin Organization of Nurse Executives. Wisconsin Council of Nurse Managers.
      Wisconsin Nurses Association. Wisconsin Health and Hospital Association. State
      Medical Society of Wisconsin.

PMID- 9197196
TI  - Nurse-midwife and physician collaboration: improving opportunities to work
      towards a healthier Wisconsin.

PMID- 9197197
TI  - Testing the viability of collaborative interdisciplinary practice in community
      focused primary health care: a case study in change.

PMID- 9197198
TI  - Nurse-midwifery at Gundersen Clinic: a twenty year review.
AB  - The twenty-year experience of the Certified Nurse-Midwife (CNM) Service at
      Gundersen Lutheran Medical Center is presented. The Service was started in
      September, 1975. From 1975 through 1995, the nurse-midwives have attended 9,120
      women in labor (32.5% of all laboring women at Lutheran Hospital). During this
      time, the CNM service perinatal mortality rate was 6.8 per 1,000 births and the
      primary cesarean section rate was 5.8%. A close working relationship between
      nurse-midwives and obstetricians is thought to be one of the main factors in the
      growth, acceptance and safety of the service.

PMID- 9197199
TI  - Medical coverage analysis for Wisconsin's Olympics: the Badger State Games.
AB  - The objective of this analysis is to determine the prevalence and severity of
      injuries encountered during the 1994-96 Badger State Summer Games Finals.
      Allocation of available medical personnel can be determined with this
      information. Medical contact with an athlete required an evaluation form to be
      completed by the health care professional covering the event. Information was
      compiled and analyzed to determine injury frequency and severity. Of the 31,580
      athletes competing over the three year period in the 11 sports provided with
      medical personnel, 285 suffered a reportable injury. Soccer and basketball had
      the highest number of reported injuries with 68 and 65 injuries respectively.
      Basketball (2.00%), cycling (1.59%), wrestling (1.50%) and roller hockey (1.24%)
      had the highest injury rates. Severity of injury determined by the number of
      injuries transported to a medical facility found wrestling (23), soccer (22),
      basketball (11), and cycling (6) with the highest numbers of severe injuries.
      Wrestling (1.27%), basketball (.34%), soccer (.32%), and cycling (.21%) had the
      highest rate of severe injury. The most common sustained injuries were found to
      be sprains, strains, skin wounds, and contusions. These four types of injuries
      made up 70.18% of the injuries sustained. In conclusion, non-physician medical
      presence may be adequate coverage in most venues at multi-sport athletic
      competitions like the Badger State Games because of the relatively low frequency
      of severe injuries.

PMID- 9197201
TI  - Heart rate and blood lactate responses to submaximal treadmill exercise in the
      normally performing standardbred trotter--age and sex variations and
      predictability from the total red blood cell volume.
AB  - The purposes of this study were to elucidate the influences of age and sex on the
      heart rate (HR, bpm) and blood lactate (LA, mmol/l) related exercise tolerance
      parameters V2000 (tread ill velocity at HR 200), VLA4 (velocity at LA 4), W200
      (power output at V2000), and WLA4 (power output at VLA4), and to establish
      reference values for these in normally performing Standardbred trotting race
      horses. A further aim was to improve the predictability of individual normal
      values by correlating them with the total red blood cell volume (CV) alone or in
      combination with the blood lactate response at V200 (LA200). In total 205 horses
      were included in the study. According to their owners and/or trainers they were
      all performing satisfactorily (in racing or training) for shortly impending
      racing. The exercise test was performed on an inclined (3.5 degrees) high speed
      treadmill and consisted of four sequentially increasing speeds, each of 2 min
      duration, aiming at a final HR at or exceeding 200 bpm. HR was monitored
      continuously and recorded in parallel with blood sampling during the last 15 s of
      each speed. Blood volume determination was done with the Evans blue dye dilution
      technique immediately after the exercise test to ensure complete emptying of the
      splenic red cell reservoir. Both age and sex influenced significantly on all
      parameters. These were also all strongly dependent on the total red cell volume.
      Consequently, it was concluded that markers for work tolerance based on heart
      rate and blood lactate responses to submaximal treadmill exercise reliably
      reflect circulatory and muscle metabolic capacities. Further, individual normal
      values are predictable from the red cell volume alone with variation coefficients
      between 5 and 9.1%, or, in combination with LA200, between 4.4 and 62%.
      Disregarding the regression with CV, predictability of normal values is improved
      by considering age and sex variations.

PMID- 9197200
TI  - Pasteurella multocida osteomyelitis by a "cat lick".

PMID- 9197202
TI  - Postpartum adrenal, pituitary and ovarian functions in dairy cows.
AB  - Postpartum stress and the resumption of pituitary and ovarian functions were
      investigated in 29 dairy cows during the first month after calving.
      Adrenocorticotropic hormone (ACTH, 25 i.u., IM) challenge tests for adrenal
      function at 8 and 22 days postpartum and gonadotropin releasing hormone (GnRH, 50
      micrograms IM) challenge tests for pituitary function at 7 and 21 days postpartum
      were conducted. Ovarian function, particularly the interval to first ovulation,
      was evaluated through weekly rectal palpation and ultrasonographic examination,
      as well as thrice weekly milk progesterone levels. Elevated basal cortisol levels
      were found in 24.1% and 20.7% of cows at 8 and 22 days postpartum, respectively.
      Adrenal response to ACTH was similar at 8 and 22 days postpartum with low, medium
      and high peak responses in 13.8%, 62.1% and 24.1% of cows, respectively. A
      moderate correlation was observed between basal and peak cortisol levels. Peak
      pituitary luteinizing hormone (LH) response was low in 65.5%, medium in 27.6% and
      high in 6.9% of cows at 7 days postpartum. Pituitary responsiveness improved by
      day 21 with low in 34.5%, medium in 37.9% and high in 27.6% of cows. About a week
      after calving, a negative correlation between peak cortisol and peak LH levels
      was observed. First ovulation occurred in 28%, 48% and 17% of postpartum cows
      during the second, third and fourth week, respectively. These results indicate a
      negative effect of peak cortisol levels on pituitary responsiveness to GnRH
      stimulation during the first week, altered adrenal and pituitary function in a
      third of the cows until the third week and restoration of ovarian function in
      most cows (93%) a month after parturition.

PMID- 9197203
TI  - Clinical assessment of udder health status of sows at time of weaning with
      special reference to bacteriology and cytology in milk.
AB  - The main objective of this study was to obtain data about the frequencies of teat
      injuries, udder skin lesions and abnormal palpatory findings of the mammary
      glands at the day of weaning and 7 days after weaning. Milk samples were
      collected from mammary glands and teats without clinical changes and from glands
      and teats showing abnormal clinical appearance. Bacteriological examination was
      performed and evaluated. The total cell content (TCC) and the polymorphonuclear
      leucocytes (PMNLs) were counted and used as indicators of inflammatory response.
      Sixty per cent of the lactations showed teat injuries and (or) udder skin lesions
      irrespective of lactation number. The prevalence of palpable changes increased
      gradually from the first to the second and subsequent lactations (15%, 30% and
      60%), the increase from the first to the second and from the first to the third
      and subsequent lactations being significant or highly significant (P < 0.05 and P
      < 0.001). The average number of teats injured per 'lactation with teat injuries'
      showed a numerical but not significant decrease (3.0, 3.2 and 2.4, respectively).
      The average number of palpable changes per 'lactation with palpable changes'
      varied from 1.7 to 2.5. The teat injuries were numerically more frequent within
      the two thoracic and first three abdominal teat pairs, varying from 11% to 16%.
      The clinical appearance of the teat injuries and palpatory changes subsided
      rapidly, 76% and 49% being scored as clinically normal when the re-examination
      was performed 7 days after weaning. Irrespective of clinical group, the milk
      collected at the day of weaning yielded non- as well as alpha- and beta
      haemolytic streptococci. The beta-haemolytic streptococci turned out to be more
      frequently isolated from milk collected from clinically abnormal glands and
      teats. The limited number of secretion samples obtained and cultured 7 days after
      weaning yielded staphylococci and Actinomyces pyogenes, which indicated a
      bacterial flora known to cause infectious mastitis. A cytological comparison
      between milk from clinically normal and abnormal mammary glands and teats
      revealed almost significantly or significantly increased levels of TCC and PMNLs
      (12.17 vs. 17.76 x 10(6) cells/ml and 1.40 vs. 2.77 x 10(6) cells/ml). A
      comparison between levels of TCC and PMNLs in milk collected from the two
      clinical groups of sows, but where the bacteriological growth turned out to be
      negative, also revealed significant increases in the levels of the two cell
      parameters emanating from clinically abnormal glands and teats. The individual
      sow, but not herd or lactation, showed a significant influence on the variation
      of TCC.

PMID- 9197204
TI  - Methods for the differentiation of giant cells in canine and feline neoplasias in
      paraffin sections.
AB  - In the following study cells with at least two cell nuclei are addressed as giant
      cells. In 47 biopsies of feline neoplasias (fibrosarcoma,
      haemangioendothelsarcoma, mammary adenocarcinoma, osteoidsarcoma, complex
      sarcoma), and 25 biopsies of canine neoplasias (malignant seminoma, mammary
      adenocarcinoma, haemangioendothelsarcoma, fibrosarcoma, osteoblastic sarcoma,
      complex sarcoma) giant cells are distinguished either as neoplastic giant cells
      or as reactive (non-neoplastic) giant cells. Cell nuclei of neoplastic giant
      cells which are labelled with the monoclonal antibody MIB 1 are mitotic active;
      cell nuclei are polymorph and can show atypical mitosis; the cytoplasmic reaction
      with tartrate resistant acid phosphatase (TRAP) is negative. Negative reactions
      with MIB 1, positive TRAP staining and homogeneous cell nuclei are distinctive
      for osteoclast-like glant cells. Other non-neoplastic giant cells (e.g. foreign
      body cells, Langhans-giant cells) are negative with both MIB 1 and TRAP. Double
      staining of paraffin sections is possible. Routine formalin-fixation, embedding
      in paraffin and decalcifying tissue samples do not interfere with MIB 1
      immunoreactions or TRAP reactions. Methodological modifications that were
      necessary for the preparation of paraffin sections from canine and feline tissue
      samples are discussed. As the presence of neoplastic giant tumour cells is an
      index for a poor prognosis in human medicine, not only the entity of the tumour
      must be named, but also the exact significance of the giant cell type:, e.g.
      fibrosarcoma with osteoclast-like giant cells, hepatic carcinoma with reactive
      giant cells, malignant seminoma with neoplastic giant cells, angiosarcoma with
      both neoplastic giant cells and osteoclast-like giant cells. This would enable
      the classification of further neoplasias dealing with clinical courses of the
      diseases. Over the past years our stains have remained stable. It is possible to
      carry out retrospective investigations with archived tissue samples and make
      permanent preparations. A reclassification and a refined form of diagnosis
      (tumour and giant cell type) would be recommended.

PMID- 9197205
TI  - Pyogranulomatous pleuritis with empyema in hunting dogs.
AB  - Nine hunting breed dogs were treated for thoracic empyema of undetermined origin.
      Seven dogs returned to normal health after combined pleural drainage by modified
      Seldinger technique and long-term chemotherapy. Two were destroyed in the early
      phase of treatment. One died and one was destroyed due to recurrence. Associated
      signs in four of the dogs included thoracic wall swellings. In two of these, very
      small foreign bodies of plant origin were found intrathoracically at surgery.
      Predominantly anaerobic commensals of the mucous membranes were isolated from
      pleural exudate. Post-mortem examination in the four cases showed productive,
      pyogranulomatous intrathoracic inflammation and pleural adhesions. It is proposed
      that inhaled small plant parts, by synergism with endogenous microorganisms of
      mucous membrane origin, may be of aetiologic importance in seemingly idiopathic
      pyogranulomatous pleuritis with empyema in hunting dogs.

PMID- 9197206
TI  - Efficacy of the combination sodium ceftiofur-flumethasone in the treatment of
      experimental Pasteurella haemolytica bronchopneumonia in calves.
AB  - Severe acute bronchopneumonia was induced in 18 conventional Friesian-Holstein
      calves by inoculating them intratracheally with Pasteurella haemolytica type A1.
      Six of the calves received no treatment and served as controls. Six of the calves
      were treated with sodium ceftiofur and six were treated with sodium ceftiofur and
      flumethasone. The mortality rate in the group of calves treated with sodium
      ceftiofur and flumethasone was significantly lower and their clinical and
      haematological parameters returned to normal significantly faster than in the
      control calves and the calves treated with sodium ceftiofur alone.

PMID- 9197207
TI  - Further characterization of alpha 2-macroglobulin binding properties of
      Actinomyces pyogenes.
AB  - Binding of 125I-labelled alpha 2-macroglobulin (alpha 2M) to Actinomyces pyogenes
      was investigated. The binding of alpha 2M proved to be time dependent, saturable,
      and could be inhibited by unlabelled alpha 2M, but not by fibrinogen,
      haptoglobin, fibronectin, or albumin. The alpha 2M binding site was sensitive to
      treatment with proteolytic enzymes and heat, indicating its protein nature. The
      dissociation constant (Kd) was 4.447 x 10(-9) M, and the number of binding sites
      per bacterial cell was calculated to be 5200. The kinetic analysis indicated an
      homogeneous population of binding sites. Binding of alpha 2M to the surface of A.
      pyogenes had no significant influence on the phagocytosis of the bacteria by
      polymorphonuclear leucocytes.

PMID- 9197208
TI  - Serologic survey for antibodies to Borrelia burgdorferi in sheep, goats and dogs
      in Cordillera Province, Bolivia.
AB  - A serosurvey for antibodies to Borrelia burgdorferi using an enzyme-linked
      immunosorbent assay (ELISA) was conducted on sheep, goat and dog serum samples
      collected in Cordillera Province, Bolivia, in 1992 Sera from 98 sheep, 218 goats
      and 43 dogs were tested. The observed seroprevalence in sheep and dogs was 0.0%,
      whereas the seropositivity rate for goat serum samples was 5.0%. Upon analysing
      10 positive sera by Western immunoblotting, five reacted against the specific
      protein antigens and all of them met the criteria for positivity on the basis of
      immunoglobulin G (IgG) bands, indicating that goats in Cordillera Province were
      exposed to B. burgdorferi. These findings, which are further proof of the
      existence of B. burgdorferi infection in Bolivia, indicate the serologic analysis
      of goats as a suitable tool for Lyme borreliosis surveillance.

PMID- 9197209
TI  - Eukaryotic and prokaryotic cell functions required for invasion of Staphylococcus
      aureus into bovine mammary epithelial cells.
AB  - Eukaryotic and prokaryotic cellular functions required for invasion of
      Staphylococcus aureus into bovine mammary epithelial cells were investigated. Two
      strains of S. aureus isolated from milk of cows with clinical mastitis, a primary
      bovine mammary epithelial cell culture and a bovine mammary epithelial cell line
      were pretreated with inhibitors of nucleic acid and protein synthesis. In
      addition, mammary epithelial cells were pretreated with inhibitors of receptor
      mediated endocytosis and oxidative phosphorylation. Protein and nucleic acid
      synthesis in prokaryotic and eukaryotic cells and eukaryotic oxidative
      phosphorylation were required for invasion of S. aureus into mammary epithelial
      cells. Inhibition of receptor-mediated endocytosis caused a significant reduction
      in the number of invading S. aureus. These results suggest that invasion of S.
      aureus into bovine mammary epithelial cells occurs through a receptor-mediated
      endocytosis process. Furthermore, eukaryotic oxidative metabolism, protein
      synthesis and nucleic acid synthesis as well as bacterial protein synthesis are
      required for bacterial invasion.

PMID- 9197210
TI  - Borna disease virus (BDV), a (zoonotic?) worldwide pathogen. A review of the
      history of the disease and the virus infection with comprehensive bibliography.
AB  - A comprehensive history of Borna disease virus (BDV) and this infection,
      including the complete bibliography, is presented. Over the last 200 years,
      descriptions of this 'head disease' of horses ('Kopfkrankheit der Pferde') have
      been given. Considerable losses in the horse population (< 0.8%) led to intensive
      clinical and (neuro-)pathological investigations of this meningitis
      cerebrospinalis which occurs with faint behavioural changes, occasionally
      followed by severe neurological symptomatology and death. The broad experimental
      host range reflects infections in nature which include horses, sheep, cattle,
      cats, dogs, rodents, ostriches, and some zoo animals. BDV infections are
      associated with phylogentically old brain areas, and the retina. Occasionally,
      expression in the autonomic nervous system occurs, besides its neurotropism BDV
      can spread to peripheral organs, especially to epithelial tissues and peripheral
      blood mononuclear cells. Infections of humans that can be monitored by
      antibodies, antigens or nucleic acids in blood samples are prominent features of
      future interest. BDV, the prototype of the family Bornaviridae is an enveloped
      spherical virus carrying an 8.9 kb single-stranded, non-segmented RNA with
      negative polarity which replicates in the nucleus. These features together with
      its considerable genetic stability make this non-cytopathogenic virus an
      evolutionary 'old pathogen' in nature.

PMID- 9197211
TI  - Polymerase chain reaction (PCR) detection of porcine Chlamydia trachomatis and
      ruminant Chlamydia psittaci serovar 1 DNA in formalin-fixed intestinal specimens
      from swine.
AB  - In previous studies chlamydiae were detected immunohistologically in the gut of
      66 out of 311 pigs. The aim of the present investigation was the classification
      of these intestinal porcine chlamydiae. For the study, DNA extracted from 52
      paraffin-embedded intestinal tissues was amplified in nested polymerase chain
      reactions (PCRs) with Chlamydia omp1 genus- and species-specific primers. Some of
      the amplification products were cloned and sequenced. In 45 cases DNA could be
      amplified with genus-specific primers. Species-specific PCR and sequencing showed
      that in 42 cases the chlamydial omp1 genotype was Chlamydia trachomatis.
      Sequenced DNA fragments were 95-99% identical with the porcine strain S45. In
      three further cases sequencing analysis provided DNA sequences which were 100%
      identical with Chlamydia psittaci B577 (serovar 1) omp1 genotype. So far as the
      authors are aware this is the first report on the occurrence of C. psittaci
      serovar 1 in pigs.

PMID- 9197212
TI  - Disordered eating behavior and microvascular complications in young women with
      insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) and eating disorders are
      relatively common among young women in North America. Their coexistence could
      lead to poor metabolic control and an increased risk of the microvascular
      complications of IDDM. METHODS: We studied 91 young women with IDDM at base line
      and four to five years later to determine the prevalence and persistence of
      disordered eating behavior (on the basis of self-reported eating and weight-loss
      practices, including the intentional omission or underdosing of insulin to
      control weight) and the association of such eating disorders with metabolic
      control, diabetic retinopathy, and urinary albumin excretion. At base line, the
      mean age of the young women was 15+/-2 years and the duration of diabetes was 7+/
      4 years. RESULTS: At base line, 26 of 91 young women (29 percent) had highly or
      moderately disordered eating behavior, which persisted in 16 (18 percent) and
      improved in 10 (11 percent). Of the 65 women with normal eating behavior at base
      line (71 percent), 14 (15 percent) had disordered eating at follow-up. Omission
      or underdosing of insulin lose weight was reported by 12 of 88 young women (14
      percent) at base line and 30 (34 percent) at follow-up (P=0.003). At base line,
      the mean (+/-SD) hemoglobin A(1c) value was higher in the group with highly
      disordered eating behavior (11.1+/-1.2 percent) than in the groups whose eating
      behavior was moderately disordered (8.9+/-1.7 percent) or nondisordered (8.7+/
      1.6 percent, P<0.001). Disordered eating at base line was associated with
      retinopathy four years later (P=0.004), when 86 percent of the young women with
      highly disordered eating behavior, 43 percent of those with moderately disordered
      eating behavior, and 24 percent of those with nondisordered eating behavior had
      retinopathy. CONCLUSIONS: Disordered eating behavior is common and persistent in
      young women with IDDM and is associated with impaired metabolic control and a
      higher risk of diabetic retinopathy.

PMID- 9197213
TI  - Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular
      carcinoma in children. Taiwan Childhood Hepatoma Study Group.
AB  - BACKGROUND: A nationwide hepatitis B vaccination program was implemented in
      Taiwan in July 1984. To assess the effect of the program on the development of
      hepatocellular carcinoma, we studied the incidence of this cancer in children in
      Taiwan from 1981 to 1994. METHODS: We collected data on liver cancer in children
      from Taiwan's National Cancer Registry, which receives reports from each of the
      country's 142 hospitals with more than 50 beds. Data on childhood liver cancer
      were also obtained from Taiwan's 17 major medical centers. To prevent the
      inclusion of cases of hepatoblastoma, the primary analysis was confined to liver
      cancers in children six years of age or older. Data were also obtained on
      mortality from liver cancer among children. RESULTS: The average annual incidence
      of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70
      per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to
      0.36 between 1990 and 1994 (P<0.01). The corresponding rates of mortality from
      hepatocellular carcinoma also decreased. The incidence of hepatocellular
      carcinoma in children 6 to 9 years of age declined from 0.52 for those born
      between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001).
      CONCLUSIONS: Since the institution of Taiwan's program of universal hepatitis B
      vaccination, the incidence of hepatocellular carcinoma in children has declined.

PMID- 9197214
TI  - Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter
      Giant Cell Myocarditis Study Group Investigators.
AB  - BACKGROUND: Idiopathic giant-cell myocarditis is a rare and frequently fatal
      disorder. We used a multicenter data base to define the natural history of giant
      cell myocarditis and the effect of treatment. METHODS: We identified 63 patients
      with idiopathic giant-cell myocarditis through journal announcements and direct
      mailings to cardiovascular centers worldwide. RESULTS: The patients consisted of
      33 men and 30 women with an average age of 42.6 years; 88 percent were white, 5
      percent were black, 5 percent were Southeast Asian or Indian, and 2 percent were
      Middle Eastern. Most presented with congestive heart failure (47 patients, or 75
      percent), ventricular arrhythmia (9 patients, or 14 percent), or heart block (3
      patients, or 5 percent), although in some cases the initial symptoms resembled
      those of acute myocardial infarction (4 patients). Nineteen percent had
      associated autoimmune disorders. The rate of survival was worse than among 111
      patients with lymphocytic myocarditis in the Myocarditis Treatment Trial
      (P<0.001); among our patients, the rate of death or cardiac transplantation was
      89 percent, and median survival was only 5.5 months from the onset of symptoms.
      The 22 patients treated with corticosteroids and cyclosporine, azathioprine, or
      both therapies survived for an average of 12.3 months, as compared with an
      average of 3.0 months for the 30 patients who received no immunosuppressive
      therapy (P=0.001). Of the 34 patients who underwent heart transplantation, 9 (26
      percent) had a giant-cell infiltrate in the transplanted heart and 1 died of
      recurrent giant-cell myocarditis. CONCLUSIONS: Giant-cell myocarditis is a
      disease of relatively young, predominantly healthy adults. Patients usually die
      of heart failure and ventricular arrhythmia unless cardiac transplantation is
      performed. Despite the possibility of fatal disease recurrence, transplantation
      is the treatment of choice for most patients.

PMID- 9197215
TI  - Clinical and neuroradiographic manifestations of eastern equine encephalitis.
AB  - BACKGROUND: Eastern equine encephalitis occurs principally along the east and
      Gulf coasts of the United States. Recognition of the neuroradiographic
      manifestations of eastern equine encephalitis could hasten the diagnosis of the
      illness and speed the response to index cases. METHODS: We reviewed all cases of
      eastern equine encephalitis reported in the United States between 1988 and 1994.
      The records of 36 patients were studied, along with 57 computed tomographic (CT)
      scans and 23 magnetic resonance imaging (MRI) scans from 33 patients. RESULTS:
      The mortality rate was 36 percent, and 35 percent of the survivors were
      moderately or severely disabled. Neuroradiographic abnormalities were common and
      best visualized by MRI. Among the patients for whom MRI scans were available, the
      results were abnormal for all eight comatose patients as well as for all three
      noncomatose patients who subsequently became comatose. The CT results were
      abnormal in 21 of 32 patients with readable scans. The abnormal findings included
      focal lesions in the basal ganglia (found in 71 percent of patients on MRI, and
      in 56 percent on CT), thalami (found in 71 percent on MRI and in 25 percent on
      CT), and brain stem (found in 43 percent on MRI and in 9 percent on CT). Cortical
      lesions, meningeal enhancement, and periventricular white-matter changes were
      less common. The presence of large radiographic lesions did not predict a poor
      outcome, but either high cerebrospinal fluid white-cell counts or severe
      hyponatremia did. CONCLUSIONS: Eastern equine encephalitis produces focal
      radiographic signs. The characteristic early involvement of the basal ganglia and
      thalami distinguish this illness from herpes simplex encephalitis. MRI is a
      sensitive technique to identify the characteristic early radiographic
      manifestations of this viral encephalitis.

PMID- 9197216
TI  - Images in clinical medicine. Aortic intramural hematoma.

PMID- 9197217
TI  - Surgery of the thoracic aorta.

PMID- 9197218
TI  - Imaging of the hepatobiliary tract.

PMID- 9197219
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 20-1997. A 74-year-old man with progressive cough, dyspnea, and
      pleural thickening.

PMID- 9197220
TI  - Eating disorders and diabetic complications.

PMID- 9197221
TI  - Prevention of primary liver cancer by immunization.

PMID- 9197222
TI  - Overriding a patient's refusal of treatment after an iatrogenic complication.

PMID- 9197223
TI  - Flower development: repressing reproduction.
AB  - The homeotic genes that determine floral organ identity in plants turn out to be
      regulated by trans-acting factors related to the Polycomb-group proteins that
      have long been known as regulators of homeotic gene expression in Drosophila.

PMID- 9197224
TI  - Immune responses: tails to teach a B cell.
AB  - The cytoplasmic domains of the membrane-bound immunoglobulin gamma and epsilon
      chains appear to mediate internalization of antigen-immunoglobulin complexes,
      which allows efficient presentation of cognate antigen at the B-cell surface.

PMID- 9197225
TI  - Microtubule dynamics: treadmilling comes around again.
AB  - Although it is generally believed that microtubules have minus ends bound to the
      centrosome and free plus ends that exhibit dynamic instability, recent
      observations show that the minus ends can be free and that modulation of dynamic
      instability at both ends can result in treadmilling and flux in interphase cells.

PMID- 9197226
TI  - Sensorimotor processing: charting the frontier.
AB  - Recordings from two cortical areas in monkeys performing complex decision tasks
      have helped define more closely the interface between 'sensory' and 'motor'
      processing.

PMID- 9197227
TI  - Genetic redundancy: screening for selection in yeast.
AB  - An unexpectedly large proportion of eukaryotic genes yield no obvious mutant
      phenotype when inactivated. An ingenious new approach using yeast allows all
      genes to be screened simultaneously for the presence of weak selection against
      lack-of-function mutations.

PMID- 9197228
TI  - Insect evolution: how did insect wings originate?
AB  - Recent developmental studies aimed at elucidating the evolutionary origin of
      insect wings highlight the difficulties of identifying homology between
      dramatically different structures.

PMID- 9197229
TI  - Gap junctions: getting the message through.
AB  - Connexin proteins make intercellular channels - gap junctions - which provide a
      direct pathway for cell-cell signaling in vertebrates. Studies of mice lacking
      connexin genes have demonstrated the need for intercellular transfer of messenger
      molecules and are uncovering the specific functions of each connexin.

PMID- 9197231
TI  - Visual cortex: a cat's-eye view of the visual system.
AB  - Optical imaging data show that the cat's visual cortex contains patches of cells
      that respond to low spatial and high temporal frequencies; outside the patches,
      cells respond to high spatial and low temporal frequencies. The results suggest a
      possible anatomical substrate for psychophysically defined spatial frequency
      channels.

PMID- 9197230
TI  - Synaptic transmission: well-placed modulators.
AB  - Metabotropic glutamate receptors are involved in the modulation of synaptic
      transmission; their localization in perisynaptic areas would appear to limit
      their activation by endogenous glutamate, but recent reports suggest that this
      strategic placement allows use-dependent activation of these synaptic modulators.

PMID- 9197232
TI  - Sexual behaviour: secrets and flies.
AB  - Recent studies of Drosophila courtship mutants provide a molecular foundation for
      sexual orientation and behaviour.

PMID- 9197233
TI  - Ribozymes: red in tooth and claw.
AB  - A population of catalytic RNA molecules has been engineered to operate and evolve
      in vitro in a continuous manner. The novel continuity of the process allows the
      propagation of many generations in a very short time and without the manual
      manipulation necessary with traditional in vitro selection techniques.

PMID- 9197234
TI  - Chemokines: what chemokine is that?
AB  - The discovery of a new and unusual member of the chemokine family illustrates the
      importance of chemoattractant diversity in the regulation of leukocyte movement
      through the body. The chemokines are now divisible into four clearly defined
      subgroups on the basis of structural and functional properties.

PMID- 9197235
TI  - Laue crystallography: Lights! Camera! action!
AB  - Recent advances in the Laue method of X-ray data collection from protein crystals
      have allowed very short-lived reaction intermediates to be observed successfully.

PMID- 9197236
TI  - Protein folding: does diffusion determine the folding rate?
AB  - A major question about protein folding is whether the coming together by
      diffusion of different segments of the polypeptide chain is rate-determining.
      This seemingly simple question has been very difficult to answer experimentally,
      but a positive result has now been obtained with one small model protein.

PMID- 9197237
TI  - The intrinsic temporal properties of alpha and beta retinal ganglion cells are
      equivalent.
AB  - BACKGROUND: Mammalian retinal ganglion cells have been traditionally classified
      on the basis of morphological and functional criteria, but as yet little is known
      about the intrinsic membrane properties of these neurons. This study has
      investigated these properties by making patch-clamp recordings from
      morphologically identified ganglion cells in the intact retina. RESULTS: The
      whole-cell configuration of the patch-clamp technique was used to assess the
      temporal tuning characteristics of alpha and beta cells, the two most extensively
      studied ganglion cell classes. Fourier analysis was used to examine discharge
      patterns in response to sinusoidal currents of different frequencies (1-50 Hz).
      With few exceptions, neurons responded in a stereotypic fashion to changes in
      temporal modulation, with their output initially increasing and then decreasing
      as a function of stimulus frequency. Moreover, peak responses in both cell
      classes were obtained at equivalent temporal frequencies. At high stimulus rates,
      response probability decreased, but the spikes remained phase-locked to the
      stimulus cycle, thereby enabling populations of cells to convey temporal
      information. A small number of ganglion cells did not show an appreciable
      decrease in output as a function of stimulus frequency, but these cells were not
      confined to either ganglion cell class. CONCLUSIONS: These findings provide the
      first evidence that the intrinsic temporal properties of alpha and beta cells are
      alike. Furthermore, the responses obtained to direct current injections were
      strikingly similar to those described previously with temporally modulated visual
      stimuli, suggesting that intrinsic membrane properties may shape the visual
      responses of alpha and beta cells to a larger degree than has been commonly
      assumed.

PMID- 9197238
TI  - Constitutively active protein phosphatase 1alpha causes Rb-dependent G1 arrest in
      human cancer cells.
AB  - BACKGROUND: The retinoblastoma protein (Rb) needs to be phosphorylated by cyclin
      dependent kinases (CDKs) before mammalian cells can enter the S phase of the cell
      cycle. As protein phosphatase 1 (PP1) activates Rb and is itself a target for
      inhibitory phosphorylation by CDKs in vitro, we asked whether any effects of PP1
      on cell cycle progression depend on its phosphorylation and are mediated through
      Rb. RESULTS: Using electrotransfer of recombinant protein into Rb-positive and Rb
      negative cells, we have compared the effects of a wild-type PP1 catalytic
      subunit, PP1alpha, and a constitutively active mutant of this subunit
      (PP1alphaT320A) on G1 progression, proliferation rates, and cell viability. In
      treated cells, PP1alpha levels were elevated 6-16-fold and remained stable for at
      least 48 hours. In Rb-positive cells, PP1alphaT320A, but not PP1alpha, caused
      cell cycle arrest in late G1, which was associated with a lack of Rb
      phosphorylation. In Rb-negative cells, neither wild-type nor mutant phosphatase
      caused any change in cell cycle progression. Increased cell death was observed in
      both Rb-positive and Rb-negative cells, however, upon introduction of excess
      PP1alpha. CONCLUSIONS: The difference between the effects of wild-type and mutant
      forms of PP1alpha suggests that PP1alpha has the potential to arrest cell growth
      in G1 unless it is inactivated by periodic phosphorylation at Thr320, presumably
      by CDKs that regulate passage through the G1-S cell cycle transition. Together,
      the effects in both cell types suggest that PP1alpha requires functional Rb to
      induce growth arrest, and that possibly another pool of PP1alpha induces cell
      death. This identifies PP1 as a potential target for therapeutic anti
      proliferative strategies.

PMID- 9197239
TI  - ARF proteins mediate insulin-dependent activation of phospholipase D.
AB  - BACKGROUND: ADP-ribosylation factors (ARFs) have been shown to activate
      phospholipase D (PLD), an enzyme modulated by extracellular signals, including
      several growth factors and, in particular, insulin. We have tested the hypothesis
      that ARF proteins are involved specifically in insulin-induced activation of PLD.
      RESULTS: We found that in membranes obtained from HIRcB cells, a cell line
      derived from Rat-1 fibroblasts that overexpresses normal human insulin receptors,
      binding of the GTP analogue GTPgammaS to purified bovine or recombinant ARF was
      enhanced in the presence of insulin. Membranes obtained from cells that
      overexpressed a mutated, nonfunctional insulin receptor failed to stimulate ARF
      activation. Insulin promoted the association of ARF proteins with membranes in
      the presence of GTPgammaS in permeabilized cells. Insulin activated PLD in
      permeabilized HIRcB cells by a process that required GTPgammaS and ARF. Azido
      gamma[32P]-GTP labelling of immunoprecipitated receptors revealed the presence of
      a unique 19 kD band; ARF proteins are approximately this size, and analysis using
      specific monoclonal antibodies demonstrated that ARF proteins
      coimmunoprecipitated with the insulin receptor. Coimmunoprecipitation of ARF with
      the receptor was inhibited by guanine nucleotides and stimulated by insulin. No
      evidence of the coprecipitation of ARF with mutant receptors could be obtained
      using azido-gamma[32P]-GTP or anti-ARF antibodies. CONCLUSIONS: The activation of
      ARF proteins is stimulated by insulin and this process plays an important role in
      insulin-mediated regulation of PLD.

PMID- 9197240
TI  - Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure,
      nuclear abnormalities and senescence.
AB  - BACKGROUND: The structure-specific ERCC1/XPF endonuclease complex that contains
      the ERCC1 and XPF subunits is implicated in the repair of two distinct types of
      lesions in DNA: nucleotide excision repair (NER) for ultraviolet-induced lesions
      and bulky chemical adducts; and recombination repair of the very genotoxic
      interstrand cross-links. RESULTS: Here, we present a detailed analysis of two
      types of mice with mutations in ERCC1, one in which the gene is 'knocked out',
      and one in which the encoded protein contains a seven amino-acid carboxy-terminal
      truncation. In addition to the previously reported symptoms of severe runting,
      abnormalities of liver nuclei and greatly reduced lifespan (which appeared less
      severe in the truncation mutant), both types of ERCC1-mutant mouse exhibited an
      absence of subcutaneous fat, early onset of ferritin deposition in the spleen,
      kidney malfunction, gross abnormalities of ploidy and cytoplasmic invaginations
      in nuclei of liver and kidney, and compromised NER and cross-link repair. We also
      found that heterozygosity for ERCC1 mutations did not appear to provide a
      selective advantage for chemically induced tumorigenesis. An important clue to
      the cause of the very severe ERCC1-mutant phenotypes is our finding that ERCC1
      mutant cells undergo premature replicative senescence, unlike cells from mice
      with a defect only in NER. CONCLUSIONS: Our results strongly suggest that the
      accumulation in ERCC1-mutant mice of endogenously generated DNA interstrand cross
      links, which are normally repaired by ERCC1-dependent recombination repair,
      underlies both the early onset of cell cycle arrest and polyploidy in the liver
      and kidney. Thus, our work provides an insight into the molecular basis of ageing
      and highlights the role of ERCC1 and interstrand DNA cross-links.

PMID- 9197241
TI  - CD45 regulates Src family member kinase activity associated with macrophage
      integrin-mediated adhesion.
AB  - BACKGROUND: Adhesion of leukocytes to the extracellular matrix and to other cells
      is mediated by members of the integrin family of adhesion molecules. Src family
      kinases are activated upon integrin-mediated adhesion. In lymphocytes, CD45 is a
      leukocyte-specific transmembrane protein tyrosine phosphatase that activates Src
      family kinases associated with B-cell and T-cell antigen receptor signaling by
      constitutive dephosphorylation of the inhibitory carboxy-terminal tyrosine
      phosphorylation site. Here, we show that CD45 is also important in downregulating
      the kinase activity of Src family members during integrin-mediated adhesion in
      macrophages. RESULTS: We found that CD45 colocalized with beta2 integrin and the
      Src family kinase p53/56(lyn) to adhesion sites in bone marrow-derived
      macrophages. Macrophages from CD45(-/-) mice were unable to maintain integrin
      mediated adhesion. In adherent macrophages, absence of CD45 led to the
      hyperphosphorylation and hyperactivation of p56/59(hck) and p53/56(lyn), but not
      of p58(c-fgr). CD45 directly inactivated p59(hck) but not p56(lck) in transient
      transfection assays. Furthermore, coexpression of CD45 with p59(hck) or p56(lyn)
      containing a tyrosine to phenylalanine mutation at the carboxy-terminal negative
      regulatory site resulted in decreased tyrosine phosphorylation of the Src family
      member kinases due to dephosphorylation of the potentiating tyrosine
      phosphorylation site within the kinase domain. CONCLUSIONS: Using primary bone
      marrow macrophages, these studies demonstrate that CD45 regulates Src family
      kinases and is required to maintain macrophage adhesion. CD45 decreases Src
      family kinase activity by dephosphorylating the tyrosine residue located within
      the kinase domain.

PMID- 9197242
TI  - The surface contraction waves of Xenopus eggs reflect the metachronous cell-cycle
      state of the cytoplasm.
AB  - Activated Xenopus laevis eggs undergo a series of surface contractions in
      response to cell-cycle progression but fall to cleave unless the sperm centrosome
      is present. These surface contraction waves (SCWs) begin at the animal pole and
      progress around the egg, occur every cell cycle and precede cleavage [1] [2] [3].
      The SCWs are biphasic, comprising a relaxation phase (SCWa) and a contraction
      phase (SCWb). To investigate how these events are linked to the underlying cell
      cycle, we studied the temporal and spatial relationship between the SCWs and
      previously characterized biochemical markers of cell-cycle progression. We found
      that the relaxation phase was a response to activated maturation-promoting factor
      (MPF). In contrast, the contraction phase required inactivation of MPF and was
      blocked when MPF activity was maintained at elevated levels. We also found that a
      wave of MPF activity traveled within the cell from the animal to the vegetal
      hemisphere. Taken together, these experiments suggest that the SCWs are a local
      response to a wave of MPF activation and inactivation. The egg cytoplasm,
      therefore, is metachronous in terms of cell-cycle progression; multiple cell
      cycle states are present and spatially distinct within the egg at the same time.

PMID- 9197243
TI  - Cell growth inhibition by the Mad/Max complex through recruitment of histone
      deacetylase activity.
AB  - BACKGROUND: The organization of chromatin is crucial for the regulation of gene
      expression. In particular, both the positioning and properties of nucleosomes
      influence promoter-specific transcription. The acetylation of core histones has
      been suggested to alter the properties of nucleosomes and affect the access of
      DNA-binding transcriptional regulators to promoters. A recently identified
      mammalian histone deacetylase (HD1) shows homology to the yeast Rpd3 protein,
      which together with Sin3 affects the transcription of several genes. Mammalian
      Sin3 proteins interact with the Mad components of the Myc/Max/Mad network of cell
      growth regulators. Mad/Max complexes may recruit mammalian Rpd3-like enzymes,
      therefore, directing histone deacetylase activity to promoters and negatively
      regulating cell growth. RESULTS: We report the identification of a tetrameric
      complex composed of Max, Mad1, Sin3B and HD1. This complex has histone
      deacetylase activity which can be blocked by the histone deacetylase inhibitors
      trichostatin A and sodium butyrate. The inhibition of cell growth by Mad1 is
      enhanced by Sin3B and HD1, as measured by colony formation assays. Furthermore, a
      Mad1-induced block of S-phase progression can be overcome by trichostatin A, as
      shown in microinjection experiments. CONCLUSIONS: The recruitment of a histone
      deacetylase by sequence-specific DNA-binding proteins provides a mechanism by
      which the state of acetylation of histones in nucleosomes and hence the activity
      of specific promoters can be influenced. The finding that Mad/Max complexes
      interact with Sin3 and HD1 in vivo suggests a model for the role of Mad proteins
      in antagonizing the function of Myc proteins.

PMID- 9197244
TI  - A mammalian DNA repair enzyme that excises oxidatively damaged guanines maps to a
      locus frequently lost in lung cancer.
AB  - BACKGROUND: Guanine residues in the genome are vulnerable to attack by free
      radicals and reactive oxygen species. A major lesion thus produced, 8-oxoguanine
      (OG), causes mutations by mis-pairing with adenine during replication. In
      bacteria and budding yeast, OG is removed from the genome through the action of
      base-excision DNA repair (BER) enzymes, which catalyze expulsion of the aberrant
      base and excision of its sugar moiety from the DNA backbone. Although OG is known
      to be produced in and cleansed from mammalian genomes, the enzymes responsible
      for OG repair in these cells have remained elusive. RESULTS: Here, we report the
      cloning and biochemical characterization of mammalian BER enzymes that
      specifically target OG residues in DNA. These 8-oxoguanine DNA glycosylases,
      hOgg1 (human) and mOgg1 (murine), are homologous to each other and to yeast Ogg1.
      They also contain an active site motif - the Helix-hairpin-Helix, Gly/Pro-rich
      Asp motif - characteristic of a superfamily of BER proteins with a similar core
      fold and active site geometry. Both hOgg1 and mOgg1 exhibit exquisite selectivity
      for the base opposite OG in DNA, operating with high efficiency only on OG base
      paired to cytosine. Furthermore, hOgg1 and mOgg1 are unable to process a panel of
      alternative lesions, including 8-oxoadenine, yet bind with high affinity to
      synthetic abasic site analogs. The proteins operate through a classical
      glycosylase/lyase catalytic mechanism; mutation of a catalytically essential
      lysine residue results in loss of catalytic potency but retention of binding to
      OG-containing oligonucleotides. The hOGG1 gene is localized on the short arm of
      chromosome 3 (3p25/26) in a region commonly deleted in cancers. CONCLUSIONS:
      These results conclusively establish the existence and identity of an 8
      oxoguanine DNA glycosylase/lyase in human and murine cells, completing the triad
      of proteins that together protect mammals from the genotoxic effects of guanine
      oxidation. The observation that at least one allele of hOGG1 is commonly deleted
      in cancer cells suggests that such cells may possess a reduced capacity to
      counter the mutagenic effects of reactive oxygen species, a deficiency that could
      increase their overall genomic instability. This speculation is fueled by recent
      observations that cells constitutively active for the Ras/Raf pathway
      constitutively produce high levels of superoxide, a known generator of OG.

PMID- 9197245
TI  - The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is
      required for late syncytial division fidelity.
AB  - BACKGROUND: Cell cycle checkpoints maintain the fidelity of the somatic cell
      cycle by ensuring that one step in the cell cycle is not initiated until a
      previous step has been completed. The extent to which cell cycle checkpoints play
      a role in the initial rapid embryonic divisions of higher eukaryotes is unclear.
      The initial syncytial divisions of Drosophila embryogenesis provide an excellent
      opportunity to address this issue as they are amenable to both genetic and
      cellular analysis. In order to study the relevance of cell cycle checkpoints in
      early Drosophila embryogenesis, we have characterized the maternal-effect grapes
      (grp) mutation, which may affect feedback control during early syncytial
      divisions. RESULTS: The Drosophila grp gene encodes a predicted serine/threonine
      kinase and has significant homology to chk1/rad27, a gene required for a DNA
      damage checkpoint in Schizosaccharomyces pombe. Relative to normal embryos,
      embryos derived from grp-mutant mothers exhibit elevated levels of DNA damage.
      During nuclear cycles 12 and 13, alignment of the chromosomes on the metaphase
      plate was disrupted in grp-derived embryos, and the embryos underwent a
      progression of cytological events that were indistinguishable from those observed
      in normal syncytial embryos exposed to X-irradiation. The mutant embryos also
      failed to progress through a regulatory transition in Cdc2 activity that normally
      occurs during interphase of nuclear cycle 14. CONCLUSION: We propose that the
      primary defect in grp-derived embryos is a failure to replicate or repair DNA
      completely before mitotic entry during the late syncytial divisions. This
      suggests that wild-type grp functions in a developmentally regulated DNA
      replication/damage checkpoint operating during the late syncytial divisions.
      These results are discussed with respect to the proposed function of the
      chk1/rad27 gene.

PMID- 9197246
TI  - MASH1 maintains competence for BMP2-induced neuronal differentiation in post
      migratory neural crest cells.
AB  - BACKGROUND: The interplay between growth factors and transcription factors in
      vertebrate neurogenesis is poorly understood. MASH1 is a basic helix-loop-helix
      (bHLH) transcription factor that is essential for autonomic neurogenesis. Bone
      morphogenetic protein (BMP) 2, and its relative BMP4, have been shown to induce
      expression of MASH1 and to promote autonomic neuronal differentiation in neural
      crest stem cells. The relationship between expression of MASH1 and the neurogenic
      competence of neural crest cells has not been investigated, however. RESULTS: We
      have examined the function of MASH1 in neurogenic competence using a population
      of immuno-isolated neural-crest-derived progenitor cells. Post-migratory neural
      crest cells isolated from fetal rat gut expressed Mash1, yet comprised a mixture
      of committed neuronal precursors and non-neuronal cells. The non-neuronal cells
      remained competent to differentiate to neurons, however, if challenged with BMP2.
      Such competence declines with time and is paralleled by a decline in Mash1
      expression in the cells. Expression of endogenous Mash1 can be maintained by
      BMP2; in turn, constitutive expression of Mash1 from a retroviral vector
      maintains competence for neuronal differentiation in response to late addition of
      BMP2. CONCLUSIONS: These data suggest that MASH1 promotes competence for
      neurogenesis, in a manner similar to its homologs, the proneural genes achaete
      scute in Drosophila. They also reveal an unexpected feedback interaction between
      BMP2 and MASH1 during neuronal differentiation. MASH1 may play multiple roles at
      successive stages of development within a neurogenic lineage, only one of which
      is revealed by a loss-of-function mutation.

PMID- 9197251
TI  - The Drosophila Beat protein is related to adhesion proteins that contain
      immunoglobulin domains.

PMID- 9197253
TI  - Modular structure of the Drosophila Beat protein.

PMID- 9197259
TI  - Single polymer dynamics in an elongational flow.
AB  - The stretching of individual polymers in a spatially homogeneous velocity
      gradient was observed through use of fluorescently labeled DNA molecules. The
      probability distribution of molecular extension was determined as a function of
      time and strain rate. Although some molecules reached steady state, the average
      extension did not, even after a approximately 300-fold distortion of the
      underlying fluid element. At the highest strain rates, distinct conformational
      shapes with differing dynamics were observed. There was considerable variation in
      the onset of stretching, and chains with a dumbbell shape stretched more rapidly
      than folded ones. As the strain rate was increased, chains did not deform with
      the fluid element. The steady-state extension can be described by a model
      consisting of two beads connected by a spring representing the entropic
      elasticity of a worm-like chain, but the average dynamics cannot.

PMID- 9197261
TI  - The role of antibody concentration and avidity in antiviral protection.
AB  - Neutralizing antibodies are necessary and sufficient for protection against
      infection with vesicular stomatitis virus (VSV). The in vitro neutralization
      capacities and in vivo protective capacities of a panel of immunoglobulin G
      monoclonal antibodies to the glycoprotein of VSV were evaluated. In vitro,
      neutralizing activity correlated with avidity and with neutralization rate
      constant, a measure of on-rate. However, in vivo, protection was independent of
      immunoglobulin subclass, avidity, neutralization rate constant, and in vitro
      neutralizing activity; above a minimal avidity threshold, protection depended
      simply on a minimum serum concentration. These two biologically defined
      thresholds of antibody specificity offer hope for the development of adoptive
      therapy with neutralizing antibodies.

PMID- 9197262
TI  - Bacterial interference caused by autoinducing peptide variants.
AB  - The synthesis of virulence factors and other extracellular proteins by
      Staphylococcus aureus is globally controlled by the agr locus, which encodes a
      two-component signaling pathway whose activating ligand is an agr-encoded
      autoinducing peptide. The cognate peptides produced by some strains inhibit the
      expression of agr in other strains, and the amino acid sequences of peptide and
      receptor are markedly different between such strains, suggesting a
      hypervariability-generating mechanism. Cross-inhibition of gene expression
      represents a type of bacterial interference that could be correlated with the
      ability of one strain to exclude others from infection or colonization sites, or
      both.

PMID- 9197263
TI  - An animal model for acute and persistent Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) is a human lymphocryptovirus that causes infectious
      mononucleosis, persists asymptomatically for life in nearly all adults, and is
      associated with the development of B cell lymphomas and nasopharyngeal
      carcinomas. A highly similar rhesus lymphocryptovirus naturally endemic in rhesus
      monkeys was used to orally infect naive animals from a pathogen-free colony. This
      animal model reproduced key aspects of human EBV infection, including oral
      transmission, atypical lymphocytosis, lymphadenopathy, activation of CD23(+)
      peripheral blood B cells, sustained serologic responses to lytic and latent EBV
      antigens, latent infection in the peripheral blood, and virus persistence in
      oropharyngeal secretions. This system may be useful for studying the
      pathogenesis, prevention, and treatment of EBV infection and associated
      oncogenesis.

PMID- 9197264
TI  - Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen
      gradient.
AB  - The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric
      oxide (NO) to cysteinebeta93, forming S-nitrosohemoglobin. Deoxygenation is
      accompanied by an allosteric transition in S-nitrosohemoglobin [from the R
      (oxygenated) to the T (deoxygenated) structure] that releases the NO group. S
      nitrosohemoglobin contracts blood vessels and decreases cerebral perfusion in the
      R structure and relaxes vessels to improve blood flow in the T structure. By thus
      sensing the physiological oxygen gradient in tissues, hemoglobin exploits
      conformation-associated changes in the position of cysteinebeta93 SNO to bring
      local blood flow into line with oxygen requirements.

PMID- 9197265
TI  - In vivo endoscopic optical biopsy with optical coherence tomography.
AB  - Current medical imaging technologies allow visualization of tissue anatomy in the
      human body at resolutions ranging from 100 micrometers to 1 millimeter. These
      technologies are generally not sensitive enough to detect early-stage tissue
      abnormalities associated with diseases such as cancer and atherosclerosis, which
      require micrometer-scale resolution. Here, optical coherence tomography was
      adapted to allow high-speed visualization of tissue in a living animal with a
      catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical
      biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal
      and respiratory tracts at 10-micrometer resolution.

PMID- 9197266
TI  - Exchange of protein molecules through connections between higher plant plastids.
AB  - Individual plastids of vascular plants have generally been considered to be
      discrete autonomous entities that do not directly communicate with each other.
      However, in transgenic plants in which the plastid stroma was labeled with green
      fluorescent protein (GFP), thin tubular projections emanated from individual
      plastids and sometimes connected to other plastids. Flow of GFP between
      interconnected plastids could be observed when a single plastid or an
      interconnecting plastid tubule was photobleached and the loss of green
      fluorescence by both plastids was seen. These tubules allow the exchange of
      molecules within an interplastid communication system, which may facilitate the
      coordination of plastid activities.

PMID- 9197267
TI  - Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during
      long-term potentiation.
AB  - Long-term potentiation (LTP), a cellular model of learning and memory, requires
      calcium-dependent protein kinases. Induction of LTP increased the phosphorus-32
      labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type
      glutamate receptors (AMPA-Rs), which mediate rapid excitatory synaptic
      transmission. This AMPA-R phosphorylation appeared to be catalyzed by Ca2+- and
      calmodulin-dependent protein kinase II (CaM-KII): (i) it correlated with the
      activation and autophosphorylation of CaM-KII, (ii) it was blocked by the CaM-KII
      inhibitor KN-62, and (iii) its phosphorus-32 peptide map was the same as that of
      GluR1 coexpressed with activated CaM-KII in HEK-293 cells. This covalent
      modulation of AMPA-Rs in LTP provides a postsynaptic molecular mechanism for
      synaptic plasticity.

PMID- 9197268
TI  - Mutation in the alpha-synuclein gene identified in families with Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime
      incidence of approximately 2 percent. A pattern of familial aggregation has been
      documented for the disorder, and it was recently reported that a PD
      susceptibility gene in a large Italian kindred is located on the long arm of
      human chromosome 4. A mutation was identified in the alpha-synuclein gene, which
      codes for a presynaptic protein thought to be involved in neuronal plasticity, in
      the Italian kindred and in three unrelated families of Greek origin with
      autosomal dominant inheritance for the PD phenotype. This finding of a specific
      molecular alteration associated with PD will facilitate the detailed
      understanding of the pathophysiology of the disorder.

PMID- 9197269
TI  - Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common
      mu1 opioid receptor mechanism.
AB  - The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol
      (Delta9-THC), and of the highly addictive drug heroin on in vivo dopamine
      transmission in the nucleus accumbens were compared in Sprague-Dawley rats by
      brain microdialysis. Delta9-THC and heroin increased extracellular dopamine
      concentrations selectively in the shell of the nucleus accumbens; these effects
      were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an
      antagonist of central cannabinoid receptors, prevented the effects of Delta9-THC
      but not those of heroin. Naloxone, a generic opioid antagonist, administered
      systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused
      into the ventral tegmentum, prevented the action of cannabinoids and heroin on
      dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on
      mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism
      located in the ventral mesencephalic tegmentum.

PMID- 9197270
TI  - Activation of corticotropin-releasing factor in the limbic system during
      cannabinoid withdrawal.
AB  - Corticotropin-releasing factor (CRF) has been implicated in the mediation of the
      stress-like and negative affective consequences of withdrawal from drugs of
      abuse, such as alcohol, cocaine, and opiates. This study sought to determine
      whether brain CRF systems also have a role in cannabinoid dependence. Rats were
      treated daily for 2 weeks with the potent synthetic cannabinoid HU-210.
      Withdrawal, induced by the cannabinoid antagonist SR 141716A, was accompanied by
      a marked elevation in extracellular CRF concentration and a distinct pattern of
      Fos activation in the central nucleus of the amygdala. Maximal increases in CRF
      corresponded to the time when behavioral signs resulting from cannabinoid
      withdrawal were at a maximum. These data suggest that long-term cannabinoid
      administration alters CRF function in the limbic system of the brain, in a manner
      similar to that observed with other drugs of abuse, and also induces
      neuroadaptive processes that may result in future vulnerability to drug
      dependence.

PMID- 9197271
TI  - Receptor-mediated activation of a MAP kinase in pathogen defense of plants.
AB  - Parsley cells recognize the fungal plant pathogen Phytophthora sojae through a
      plasma membrane receptor. A pathogen-derived oligopeptide elicitor binds to this
      receptor and thereby stimulates a multicomponent defense response through
      sequential activation of ion channels and an oxidative burst. An elicitor
      responsive mitogen-activated protein (MAP) kinase was identified that acts
      downstream of the ion channels but independently or upstream of the oxidative
      burst. Upon receptor-mediated activation, the MAP kinase is translocated to the
      nucleus where it might interact with transcription factors that induce expression
      of defense genes.

PMID- 9197272
TI  - Differential requirements for survival and proliferation of CD8 naive or memory T
      cells.
AB  - The requisite molecular interactions for CD8 T cell memory were determined by
      comparison of monoclonal naive and memory CD8(+) T cells bearing the T cell
      receptor (TCR) for the HY antigen. Naive T cells required only the right major
      histocompatibility complex (MHC) class I-restricting molecule to survive; to
      expand, they also needed antigen. In contrast, for survival, memory cells did not
      require the restricting MHC allele, but needed only a nonspecific class I; for
      expansion the correct class I, but not antigen, was required. Thus, maintenance
      of CD8 T cell memory still required TCR-MHC class I interactions, but memory T
      cells may have a lower functional activation threshold that facilitates secondary
      responses.

PMID- 9197273
TI  - Distribution of the metabotropic glutamate receptor subtype mGluR5 in rat
      midbrain periaqueductal grey and relationship with ascending spinofugal
      afferents.
AB  - The periaqueductal grey matter (PAG) is known to adjust somatic and
      neurovegetative elements of the defence behaviour. We have used specific
      polyclonal antibodies to examine the distribution of the metabotropic glutamate
      receptor subtype 5 (mGluR5) in this region. Immunolabelling for mGluR5 displayed
      a net preference for dorsolateral areas at rostral and intermediate levels.
      Electronmicroscopic examination revealed that mGluR5 is expressed in neuronal
      perikarya and in dendrites receiving synaptic contacts of Gray I type. To
      investigate the possible relevance of mGluR5 to integration of somatosensory
      information, spinoannular (SA) neurones were peroxidase-labelled and their
      relationship with mGluR5-expressing PAG neurones was examined at the
      ultrastructural level. A number of synaptic terminals of the SA pathway
      established synaptic contact of asymmetric type onto mGluR5-immunoreactive
      dendrites. It is suggested that mGluR5 might be involved in the temporal
      integration of somatosensory inputs to the PAG.

PMID- 9197274
TI  - Protein kinase A inhibitor attenuates levodopa-induced motor response alterations
      in the hemi-parkinsonian rat.
AB  - Chronically administered levodopa, the standard treatment for Parkinson's
      disease, is ultimately associated with disabling alterations in motor response.
      To evaluate the possible contribution of striatal cAMP-dependent protein kinase A
      (PKA) signaling pathways to these response modifications, the acute effects of a
      PKA inhibitor, Rp-cAMPS, on motor response changes attending chronic, twice-daily
      administration of levodopa were measured in 6-hydroxydopamine lesioned hemi
      parkinsonian rats. A single intrastriatal injection of Rp-cAMPS (2.5 or 25
      microg) attenuated both the shortened duration and augmented intensity of
      levodopa-induced turning in a dose dependent manner. Rp-cAMPS completely
      normalized motor responses to a dopamine D1 agonist (SKF 38392), but had no
      effect on those to a dopamine D2 agonist (quinpirole). These results suggest that
      D1 receptor-mediated PKA activation may contribute to the development of the
      altered motor responses associated with chronic levodopa treatment.

PMID- 9197275
TI  - Reduced sympathetic sprouting occurs in dorsal root ganglia after axotomy in mice
      lacking low-affinity neurotrophin receptor.
AB  - Following sciatic nerve injury, sympathetic axons sprout into the L5 dorsal root
      ganglion (DRG). The low-affinity neurotrophin receptor (p75) is strongly
      expressed by glial cells in DRG following axotomy. We tested the hypothesis that
      p75 is involved in this sympathetic sprouting by comparing sprouting following
      sciatic nerve cut in wild-type (CD1) and p75 knockout mice. Twenty-one days after
      injury sympathetic sprouting had occurred in both mouse strains, though the
      extent of sprouting (measured as length of sprouts per unit area of DRG) was less
      in p75 knockout mice. We conclude that p75 expression enhances, but is not
      required for, sympathetic sprouting.

PMID- 9197276
TI  - GnRH inhibits neuronal activity in the ventral tegmental area of the estrogen
      primed ovariectomized rat.
AB  - In urethane-anesthetized ovariectomized rats, estrogen-sensitive descending
      neurons were identified in the midbrain ventral tegmental area (VTA), based on
      estrogen-induced changes in the excitability in antidromic responses to midbrain
      central gray stimulation. Estrogen increased the threshold and decreased the
      firing rate of the identified neurons. Responses of the identified neurons to the
      microiontophoresis of gonadotropin-releasing hormone (GnRH) or D-Phe2, D-Ala6
      GnRH, a behaviorally active analog, but not to glutamate or gamma-aminobutyric
      acid (GABA), depended on estrogen. In the ovariectomized rat, GnRH excited a few
      neurons; the analog had no effect. GnRH suppressed spontaneous or glutamate
      induced firing in almost all neurons in the estrogen-primed rat. The analog had
      mixed effects. The facilitation of female rat sexual behavior induced by infusion
      of GnRH in the VTA is due to the inhibition of VTA neurons.

PMID- 9197277
TI  - Increased A beta 42(43)-plaque deposition in early-onset familial Alzheimer's
      disease brains with the deletion of exon 9 and the missense point mutation
      (H163R) in the PS-1 gene.
AB  - Cerebral amyloid deposition is a neuropathological hallmark for Alzheimer's
      disease (AD). Immunohistochemical analysis of two A beta species (A beta 42/43
      and A beta 40) deposition was undertaken using the carboxyl end-specific
      antibodies to determine the molecular alteration of these species in the brains
      of patients whose presenilin 1 (PS-1) gene, the major causative gene for the
      early-onset familial AD, bears the point mutation (H163R) and the deletion of
      exon 9. We found a marked increase in A beta 42-plaque deposition in brains of
      patients with PS-1 mutations compared with that in brains of those with sporadic
      AD. The results of immunohistochemical analysis indicate that both mutation and
      deletion in the PS-1 gene promote deposition of A beta 42-plaques indicating the
      pathological association of PS-1 and betaAPP/A beta 42 in early-onset familial
      AD.

PMID- 9197278
TI  - Decrease of immunoreactive catalase protein in specific areas of ageing rat
      brain.
AB  - The activity of catalase, the main enzyme responsible for detoxification against
      hydrogen peroxide, decreases in specific brain areas of aged rats. The reduction
      of enzyme activity appears to be the consequence of a decreased protein
      expression rather than an impaired function of the native enzyme. In fact,
      diminution of the immunoreactive protein parallels enzyme activity decrease.
      Since the extent of decrease of both activity and protein content was observed to
      be area dependent, we hypothesise that this phenomenon may underlie, at least in
      part, the increased susceptibility of specific brain regions to oxidative insults
      observed in pathological situations related to ageing.

PMID- 9197279
TI  - Augmentation of opioid induced antinociception by the atypical antipsychotic drug
      risperidone in mice.
AB  - Risperidone is a novel atypical neuroleptic with a favorable profile of side
      effects due to its unique pharmacological activity: it exhibits both potent
      dopamine D2 and 5-HT2 receptor blocking activity, as well as high affinity for
      alpha1 and alpha2 adrenergic receptors and histamine H1 receptor. We found that
      risperidone has a potent antinociceptive effect in the tailflick assay with an
      ED50 of 26.4 mg/kg. This effect of risperidone was antagonized by naloxone (P <
      0.05). This sensitivity to naloxone indicates that at least some of the analgesic
      effects of risperidone are mediated by an opioid mechanism of action. beta-FNA
      (mu1 mu2-antagonist), naloxonazine (mu1-antagonist) and norbinaltorphamine (nor
      BNI; kappa1-analgesia) reversed risperidone antinociceptive effect (P < 0.05).
      Naltrindole (delta-antagonist) only partially reversed risperidone
      antinociceptive effect. We found that the sensitivity of risperidone
      antinociceptive effect to selective antagonists implies involvement of mu1-, mu2-
      and kappa1-opioid and to a lesser extent delta-opioid mechanisms. These results
      suggest a possible role for risperidone both in the management of pain and in the
      management of opiate withdrawal and detoxification.

PMID- 9197280
TI  - Capsazepine, a vanilloid receptor antagonist, inhibits nicotinic acetylcholine
      receptors in rat trigeminal ganglia.
AB  - Vanilloid receptors are activated by capsaicin, the pungent ingredient in hot
      pepper. They are also specifically and competitively inhibited by capsazepine
      (CPZ). To determine whether CPZ is specific to vanilloid receptors, its effects
      were tested on the currents evoked by nicotine in rat trigeminal ganglia. We
      found that 10 microM CPZ, a concentration frequently used to inhibit capsaicin's
      physiological responses attributed to capsaicin, reversibly inhibits (40%) the
      magnitude of the currents activated by 100 microM nicotine. We conclude that 10
      microM capsazepine can alter the effects of channels other than those activated
      by capsaicin, and thus caution must be used in attributing all the CPZ-sensitive
      physiological effects to those only produced by blocking of vanilloid receptors.

PMID- 9197281
TI  - trkA and trkC expression is increased in human diabetic skin.
AB  - Nerve growth factor (NGF) is reduced in epidermal keratinocytes in human diabetic
      skin, and this decrease has been related to dysfunction of cutaneous sensory
      fibres. In vitro studies show that keratinocytes express both NGF and its high
      affinity receptor, trkA, and that NGF may increase keratinocyte proliferation and
      its own expression via an autocrine loop. However, the level of trkA expression
      in vivo by keratinocytes in normal and diabetic skin is unknown. We have
      therefore measured trkA expression in calf skin biopsies from patients with early
      subclinical diabetic neuropathy and control subjects, using in situ hybridisation
      combined with image analysis quantification. Expression of trkC was also studied,
      as its endogenous ligand neurotrophin-3 (NT-3) is related to NGF, and is present
      in human epidermis. Hybridisation signal was seen for both trkA and trkC
      localised throughout the epidermal layer of control skin, with a higher density
      of silver grain deposition observed for trkA mRNA. However, in diabetic epidermis
      there was a significant increase (P < 0.001) for both trk A (control, 0.178 +/-
      0.013; diabetic, 0.304 +/- 0.032; mean silver grain counts/microm2 +/- SEM) and
      trkC expression (controls, 0.059 +/- 0.004; diabetics, 0.191 +/- 0.010). The up
      regulation of epidermal trk receptors may result from decreased autocrine
      neurotrophin action, and could represent a compensatory mechanism.

PMID- 9197282
TI  - Nicotine regulates mRNA level of tyrosine hydroxylase gene but not that of
      nicotinic acetylcholine receptor genes in PC12 cells.
AB  - To understand the molecular mechanism of nicotine addiction, we examined the mRNA
      level of the tyrosine hydroxylase (TH) gene and that of the nicotinic
      acetylcholine receptor (nAChR) genes by long-term nicotine treatment. The
      transcript levels of the four subunit genes of the nAChR (alpha3, alpha5, alpha7,
      and beta4) were down-regulated by the treatment with forskolin, whereas the mRNA
      levels of the TH gene was increased in PC12 cells. By long-term nicotine
      treatment, the mRNA level of the nAChR genes did not change, but transcript
      levels of alpha3, alpha5, alpha7, and beta4 nAChR genes were still negatively
      regulated by forskolin. However, the mRNA level of TH gene did not change by
      forskolin under long-term nicotine treatment. The TH gene may be regulated by a
      nicotine-related signaling pathway, whereas alpha3, alpha5, alpha7, and beta4
      nAChR genes may be further regulated by a protein kinase A (PKA) pathway under
      long-term nicotine treatment.

PMID- 9197283
TI  - Effects of low doses of glycosaminoglycans and insulin-like growth factor-I on
      motor neuron disease in wobbler mouse.
AB  - In this study we examined the effects of insulin-like growth factor-I (IGF-I) and
      of glycosaminoglycans (GAGs) on the progressive motor neuron disease in wobbler
      mice. After clinical diagnosis at age 3 weeks, mice received daily subcutaneous
      injections of IGF-I, or GAGs, or saline for 3 weeks. The histometric analysis
      revealed that biceps muscle fiber diameter was reduced in wobbler mice and that
      treatments with GAGs and IGF-I prevented such a drop. The number of atrophic
      small fibers was markedly reduced and that of the larger ones augmented. No
      effects on body growth and biceps muscle weight were observed. The combined AChE
      silver staining revealed that both treatments promoted intramuscular axonal
      sprouting. The typical decline of grip strength in wobbler mice was also
      prevented. This study suggests that GAGs and IGF-I administrations can retard the
      onset of motor deficit, and reduce muscle atrophy in wobbler mice.

PMID- 9197284
TI  - Neuroprotective effects of the GABA(A) receptor partial agonist U-101017 in 3
      acetylpyridine-treated rats.
AB  - The neuroprotective effects of U-101017, [7-chloro-5-[cis-3,5
      dimethylpiperazine)carbonyl]-imidazole[1,5a]quinoli ne-3-carboxylate], a GABA(A)
      receptor partial agonist, were investigated in 3-acetylpyridine (3-AP) treated
      Wistar rats. A significant (P < 0.01) reduction in both cGMP and ATP in the
      cerebellum was observed at 96 h after treatment with 3-AP (500 micromol/kg i.p.).
      Oral administration of U-101017 before and after treatment with 3-AP
      significantly attenuated 3-AP-induced decreases in cGMP and ATP, and this effect
      was dose related. Consistent with the neurochemical effect, U-101017 prevented 3
      AP-induced loss of motor coordination. Treatment with U-101017 partially, but
      significantly (P < 0.01) prevented the loss of inferior olivary neurons. U-101017
      had no significant effect on body temperature. Thus, hypothermia was not involved
      in neuroprotective effects of U-101017. Co-administration of flumazenil with each
      treatment of U-101017 blocked the neuroprotective effect of U-101017, indicating
      that it mediated neuroprotection via the benzodiazepine binding sites on the
      GABA(A) receptor complex. Delayed administration of U-101017 at various time
      intervals after treatment with 3-AP demonstrated a significant neuroprotective
      effect even at 8 h, suggesting that this drug has a wide therapeutic window.

PMID- 9197285
TI  - Nitric oxide modulates synaptic glutamate release during anoxia.
AB  - The ability of nitric oxide to enhance vesicular glutamate release during anoxia
      was examined in the present study. Whole-cell patch clamp recordings were
      obtained from CA1 pyramidal neurons in rat hippocampal slices perfused in media
      containing tetrodotoxin. These cells exhibit spontaneous inward currents
      previously identified as glutamatergic miniature excitatory postsynaptic currents
      (mEPSCs). The frequency of these mEPSCs increases during exposure to anoxia. The
      anoxia-induced increase in frequency is reduced when experiments are performed in
      the presence of the competitive nitric oxide (NO)-synthase inhibitors N(G)-nitro
      L-arginine methyl ester and N(G)-nitro-L-arginine, as well as reduced hemoglobin.
      Arginine reversed the suppression by the NO-synthase inhibitors. The N-methyl-D
      aspartate (NMDA) receptor antagonists 3-(2-carboxypiperazine-4-yl)propyl-1
      phosphonic acid and MK-801 also suppressed the anoxia-induced increase in mEPSC
      frequency. These data indicate that NMDA receptor-activated NO production may
      enhance vesicular synaptic glutamate release, which would in turn contribute to
      excitotoxicity during hypometabolic states.

PMID- 9197286
TI  - Tyrosine hydroxylase (TH)-only-immunoreactive non-catecholaminergic neurons in
      the brain of wild mice or the human TH transgenic mice do not contain GTP
      cyclohydrolase I.
AB  - We previously reported the presence of transiently tyrosine hydroxylase (TH)-only
      immunoreactive (ir), non-catecholaminergic (non-CAnergic) neurons in some brain
      regions of postnatal mice; anterior olfactory nucleus, medial geniculate nucleus,
      and spinal trigeminal nucleus, where CAnergic terminals but not cell bodies are
      present in the adult wild mouse. These transiently TH-ir brain regions of the
      postnatal wild mouse showed stable TH-immunoreactivity in the adult brain of the
      human TH transgenic (hTHTg) mice. TH expression was also observed in the nucleus
      parabigeminalis of the hTHTg mice. Using the antiserum against GTP cyclohydrolase
      I (GCH), first rate-limiting enzyme of the biosynthesis of tetrahydrobiopterin
      (BH4), the cofactor for TH, we proved that these TH-only-ir neurons in the wild
      mice and in the hTHTg mice were not stained with the antiserum against GCH. The
      results indicate that these TH-only-ir neurons which do not synthesize the BH4
      cofactor do not produce dihydroxyphenylalanine, suggesting a new unknown function
      of TH in these neurons.

PMID- 9197288
TI  - Identification and diurnal studies of pineal and serum 5-methoxytryptamine in the
      rat and quail.
AB  - Picomole to femtomole per gland/ml levels of 5-methoxytryptamine (5MT) in the
      pineal gland and serum of the rat and quail were determined, in the absence of a
      monoamine oxidase inhibitor, by using the ultra-sensitive technique of capillary
      column gas chromatography/electron-capture negative ion chemical ionization mass
      spectrometry. Diurnal rhythms of pineal 5MT with high levels at mid-light and low
      levels at mid-dark were found in both species, while serum 5MT levels showed less
      or no diurnal variations. The definitive presence of 5MT in the pineal gland and
      blood circulation provides further evidence that it is potentially a
      neurohormone. Whether 5MT is implicated in the photoperiodic responses and/or
      other physiological functions of animals, however, remains to be investigated.

PMID- 9197287
TI  - The status and organization of astrocytes, oligodendroglia and microglia in
      grafts of fetal rat cerebral cortex.
AB  - Immunohistochemical methods were used to study the status and organization of
      astrocytes, oligodendroglia and microglia in fetal cerebral cortical tissue
      grafted on to the dorsal surface of the midbrain in newborn host rats. Grafts
      were examined 1-6 months posttransplantation. All grafts contained large numbers
      of hypertrophied, intensely glial fibrillary acidic protein-positive astrocytes.
      Microglia were also activated, displaying slightly increased levels of OX-42
      immunoreactivity. The grafts consisted of lobules of gray matter which were
      separated by bands of myelinated fibres associated with large numbers of Rip
      positive oligodendroglia. These glial cells had a relatively normal morphology.
      The density of astrocytes and microglia was reduced in these white matter-like
      regions. In association with chronic changes in glial reactivity, transplants
      also expressed increased levels of chondroitin sulphate proteoglycans (CS-56
      antibody). The observed changes in glial cell phenotype and extracellular matrix
      in cortical transplants are likely to affect neuronal physiology and connectivity
      in a number of ways, and highlight the importance of studying both glia and
      neurons in order to gain a more comprehensive picture of the long-term functional
      potential of fetal brain grafts.

PMID- 9197289
TI  - Low-flow (1 l/min) sevoflurane: is it safe?

PMID- 9197290
TI  - The influence of nitric oxide in adult respiratory distress syndrome when Pv(O2)
      is varied.

PMID- 9197291
TI  - Effects of low-flow sevoflurane anesthesia on renal function: comparison with
      high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.
AB  - BACKGROUND: The safety of low-flow sevoflurane anesthesia, during which
      CF2=C(CF3)-O-CH2F (compound A) is formed by sevoflurane degradation, in humans
      has been questioned because compound A is nephrotoxic in rats. Several reports
      have evaluated renal function after closed-circuit or low-flow sevoflurane
      anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers.
      However, these are not the more sensitive tests for detecting renal damage. This
      study assessed the effects of low-flow sevoflurane anesthesia on renal function
      using not only BUN and serum creatinine but also creatinine clearance and urinary
      excretion of kidney-specific enzymes, and it compared these values with those
      obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.
      METHODS: Forty-eight patients with gastric cancer undergoing gastrectomy were
      studied. Patients were randomized to receive sevoflurane anesthesia with fresh
      gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow
      sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1
      l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was
      oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration
      of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the
      low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used
      instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted
      to eliminate rebreathing. The compound A concentration was measured by gas
      chromatography. Gas samples taken from the inspiratory limb of the circle system
      at 1-h intervals were analyzed. Blood samples were obtained before and on days 1,
      2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour
      urine samples were collected before anesthesia and for each 24-h period from 0 to
      72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and
      alanine aminopeptidase. RESULTS: The average inspired concentration of compound A
      was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this
      concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group.
      Postanesthesia BUN and serum creatinine concentrations decreased, creatinine
      clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine
      aminopeptidase excretion increased in all groups compared with preanesthesia
      values, but there were no significant differences between the low-flow
      sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal
      function parameter at any time after anesthesia. CONCLUSIONS: The only difference
      between the low-flow and high-flow sevoflurane groups was compound A formation,
      and postanesthesia laboratory data showed no significant effects of compound A
      formation during sevoflurane anesthesia on renal function. No significant effects
      on renal function were observed in either the low-flow or high-flow sevoflurane
      groups compared with the low-flow isoflurane group.

PMID- 9197292
TI  - Assessment of low-flow sevoflurane and isoflurane effects on renal function using
      sensitive markers of tubular toxicity.
AB  - BACKGROUND: Carbon dioxide absorbents degrade sevoflurane, particularly at low
      gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether
      (compound A). Compound A causes renal proximal tubular injury in rats but has had
      no effect on blood urea nitrogen (BUN) or creatinine concentrations in patients.
      This investigation compared the effects of low-flow sevoflurane and isoflurane on
      renal tubular function in surgical patients using conventional (BUN and
      creatinine) and finer indices of renal injury, specifically those biomarkers
      sensitive for compound A toxicity in rats (glucosuria, proteinuria, and enzymuria
      [N-acetyl-beta-D-glucosaminidase (NAG) and alpha-glutathione-S-transferase (alpha
      GST)]). METHODS: Consenting patients with normal preoperative renal function at
      two institutions were randomized to receive sevoflurane (n = 36) or isoflurane (n
      = 37) in oxygen and air. Total gas flow was 1 l/min, opioid doses were minimized,
      and barium hydroxide lime was used to maximize anesthetic degradation.
      Inspiratory and expiratory compound A concentrations were quantified every 30-60
      min. Blood and urine were obtained before and 24-72 h after anesthesia for
      laboratory evaluation. RESULTS: Sevoflurane and isoflurane groups were similar
      with respect to age, weight, sex, American Society of Anesthesiologists status,
      anesthetic duration (3.7 or 3.9 h), and anesthetic exposure (3.6 or 3 minimum
      alveolar concentration [MAC]-hour). Maximum inspired compound A concentration
      (mean +/- standard deviation) was 27 +/- 13 ppm (range, 10-67 ppm). Areas under
      the inspired and expired compound A concentration versus time curves (AUC) were
      79 +/- 54-ppm-h (range, 10-223 ppm-h) and 53 +/- 40 ppm-h (range, 6-159 ppm-h),
      respectively. There was no significant difference between anesthetic groups in
      postoperative serum creatinine or BUN, or urinary excretion of protein, glucose,
      NAG, proximal tubular alpha GST, or distal tubular pi GST. There was no
      significant correlation between compound A exposure (AUC) and protein, glucose,
      NAG, alpha GST, or pi GST excretion. Postoperative alanine and aspartate
      aminotransferase concentrations were not different between the anesthetic groups,
      and there were no significant correlations between compound A exposure and
      alanine or aspartate aminotransferase concentrations. CONCLUSIONS: The renal
      tubular and hepatic effects of low-flow sevoflurane and isoflurane were similar
      as assessed using both conventional measures of hepatic and renal function and
      more sensitive biochemical markers of renal tubular cell necrosis. Moderate
      duration low-flow sevoflurane anesthesia, during which compound A formation
      occurs, appears to be as safe as low-flow isoflurane anesthesia.

PMID- 9197293
TI  - Hypoxic pulmonary vasoconstriction in nonventilated lung areas contributes to
      differences in hemodynamic and gas exchange responses to inhalation of nitric
      oxide.
AB  - BACKGROUND: Enhancement of hypoxic pulmonary vasoconstriction (HPV) in
      nonventilated lung areas by almitrine increases the respiratory response to
      inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome
      (ARDS). Therefore the authors hypothesized that inhibition of HPV in
      nonventilated lung areas decreases the respiratory effects of NO. METHODS: Eleven
      patients with severe ARDS treated by venovenous extracorporeal lung assist were
      studied. Patients' lungs were ventilated at a fraction of inspired oxygen
      (F[I(O2)]) of 1.0. By varying extracorporeal blood flow, mixed venous oxygen
      tension (P[O2]; partial oxygen pressure in mixed venous blood [PV(O2)]) was
      adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal
      gas flow was adjusted to prevent changes in mixed venous carbon dioxide tension
      [PV(CO2)]). Hemodynamic and gas exchange variables were measured at each level
      before, during, and after 15 ppm NO. RESULTS: Increasing PV(O2) from 47 to 84
      mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P <
      0.05) and pulmnonary vascular resistance index (PVRI; P < 0.05) and in an
      increase in intrapulmonary shunt (Q[S]/Q[T]; P < 0.05). PV(CO2) and cardiac index
      did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high
      PV(O2), NO-induced decrease in Q(S)/Q(T) was independent of baseline PV(O2). In
      response to NO, arterial P(O2) increased more and arterial oxygen saturation
      increased less at high compared with low PV(O2). CONCLUSION: In patients with
      ARDS, HPV in nonventilated lung areas modifies the hemodynamic and respiratory
      response to NO. The stronger the HPV in nonventilated lung areas the more
      pronounced is the NO-induced decrease in PAP-PAWP. In contrast, the NO-induced
      decrease in Q(S)/Q(T) is independent of PV(O2) over a wide range of PV(O2)
      levels. The effect of NO on the arterial oxygen tension varies with the level of
      PV(O2) by virtue of its location on the oxygen dissociation curve.

PMID- 9197294
TI  - Concentration-effect relations for intravenous lidocaine infusions in human
      volunteers: effects on acute sensory thresholds and capsaicin-evoked hyperpathia.
AB  - BACKGROUND: Preclinical studies have emphasized that persistent small afferent
      input will induce a state of central facilitation that can be regulated by
      systemically administered lidocaine. The authors extended these preclinical
      studies to human volunteers by examining the concentration-dependent effects of
      intravenous lidocaine on acute sensory thresholds and facilitated processing
      induced by intradermal capsaicin. METHODS: Fifteen healthy persons received a
      lidocaine or a placebo infusion. A computer-controlled infusion pump targeted
      sequential stepwise increases in plasma lidocaine concentration steps of 1, 2,
      and 3 microg/ml. At each plasma concentration, neurosensory testing (thermal and
      von Frey hair test stimulation) were performed. After completing the tests at the
      3 microg/ml plasma lidocaine level, intradermal capsaicin was injected into the
      volar aspect of the left forearm, and the flare response and hyperalgesia to von
      Frey hair stimulation, stroking, and heat was assessed. RESULTS: The continuous
      infusion of lidocaine and placebo had no significant effect on any stimulus
      threshold. Although intravenous lidocaine resulted in a decrease in all secondary
      hyperalgesia responses, this was only significant for heat hyperalgesia.
      Intravenous lidocaine resulted in a significant decrease in the flare response
      induced by intradermal capsaicin. CONCLUSIONS: These studies suggest that the
      facilitated state induced by persistent small afferent input human pain models
      may predict the activity of agents that affect components of nociceptive
      processing that are different from those associated with the pain state evoked by
      "acute" thermal or mechanical stimuli. Such insight may be valuable in the
      efficient development of novel analgesics for both neuropathic and post-tissue
      injury pain states.

PMID- 9197295
TI  - Xenon provides faster emergence from anesthesia than does nitrous oxide
      sevoflurane or nitrous oxide-isoflurane.
AB  - BACKGROUND: Xenon, an inert gas with anesthetic properties (minimum alveolar
      concentration [MAC] = 71%), has an extremely low blood:gas partition coefficient
      (0.14). Therefore, we predicted that xenon would provide more rapid emergence
      from anesthesia than does N2O+isoflurane or N2O+sevoflurane of equivalent MAC.
      METHODS: Thirty American Society of Anesthsiologists class I or II patients
      undergoing total abdominal hysterectomy were randomly assigned to receive 60%
      xenon, 60% N2O + 0.5% isoflurane, or 60% N2O + 0.70% sevoflurane (all
      concentrations are end-tidal: n = 10 per group). After placement of an epidural
      catheter, anesthesia was induced with standardized doses of midazolam,
      thiopental, and fentanyl. Thirty minutes later, xenon, N2O+isoflurane, or
      N2O+sevoflurane was started as previously assigned. These regimens were
      supplemented with epidural anesthesia with mepivacaine so that the mean arterial
      pressure and heart rate were controlled within 20% of the preoperative values. At
      the end of operation lasting approximately 2 h, all inhalational anesthetics were
      discontinued, and the patients were allowed to awaken while breathing
      spontaneously on an 8 l/min inflow of oxygen. A blinded investigator recorded the
      time until the patient opened her eyes on command (T1), was judged ready for
      extubation (T2), could correctly state her name, her date of birth, and the name
      of the hospital (T3), and could count backward from 10 to 1 in less than 15 s
      (T4). RESULTS: Emergence times from xenon anesthesia were: T1, 3.4 +/- 0.9 min;
      T2, 3.6 +/- 1 min; T3, 5.2 +/- 1.4 min; and T4, 6.0 +/- 1.6 min (mean +/- SD).
      These were one half to one third of those from N2O+sevoflurane (T1, 6.0 +/- 1.7
      min; T4, 10.5 +/- 2.5 min) or N2O+isoflurane (T1, 7.0 +/- 1.9 min; T4, 14.3 +/-
      2.8 min) anesthesia. The three groups did not differ in terms of patient
      demographics, the duration of anesthesia, the amount of epidural mepivacaine
      administered, or the postoperative pain rating. No patient could recalls
      intraoperative events. CONCLUSIONS: Emergence from xenon anesthesia is two or
      three times faster than that from equal-MAC N2O+isoflurane or N2O+sevoflurane
      anesthesia.

PMID- 9197296
TI  - Alfentanil, but not amitriptyline, reduces pain, hyperalgesia, and allodynia from
      intradermal injection of capsaicin in humans.
AB  - BACKGROUND: Intradermal injection of capsaicin produces brief pain followed by
      hyperalgesia and allodynia in humans, and the latter effects are mediated by
      spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to
      antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought
      to determine the effect of amitriptyline alone and with the opioid alfentanil on
      hyperalgesia and allodynia produced by intradermal injection of capsaicin.
      METHODS: Forty-six healthy volunteers in the general clinical research center
      received repeated intradermal injections of capsaicin (100 microg) alone or
      before and after systemic injection of 4 mg midazolam, 25 mg amitriptyline,
      alfentanil by computer-controlled infusion, or amitriptyline plus alfentanil.
      Acute pain and areas of mechanical hyperalgesia and allodynia were determined at
      specified intervals. Blood was obtained for alfentanil and amitriptyline assay.
      RESULTS: Capsaicin injection produced acute pain followed by hyperalgesia and
      allodynia. Alfentanil reduced these pain responses in a plasma-concentration
      dependent manner, and reduction in hyperalgesia and allodynia correlated with
      reduction in acute pain. Amitriptyline alone had no effect and did not potentiate
      alfentanil. Alfentanil produced concentration-dependent nausea, an effect
      diminished by amitriptyline. DISCUSSION: These data correspond with previous
      studies in volunteers demonstrating reduction in hyperalgesia and allodynia after
      intradermal injection of capsaicin by systemically administered opioids, and they
      suggest that this reduction may be secondary to reduced nociceptive input by
      acute analgesia. These data do not support the use of acute systemic
      administration of amitriptyline for acute pain, hyperalgesia, and allodynia,
      although the roles of chronic treatment and spinal administration are being
      investigated.

PMID- 9197297
TI  - Effects of concentration and volume of 2-chloroprocaine on epidural anesthesia in
      volunteers.
AB  - BACKGROUND: Effect of local anesthetic concentration and volume on the spread and
      density of epidural anesthesia is unclear. This study was performed to delineate
      effects of a threefold difference in concentration and volume of 2-chloroprocaine
      on epidural anesthesia. METHODS: Twelve healthy volunteers underwent lumbar
      epidural anesthesia with 300 mg of 2-chloroprocaine as a 3% (10 ml) and a 1% (30
      ml) solution in a randomized, double-blind, balanced, crossover fashion. Sensory
      block was assessed with pinprick, touch (calibrated plastic filament), cold, and
      electrical stimulation. Motor block was assessed at the quadriceps and
      gastrocnemius muscles with isometric force dynamometry. Differences between
      solutions were assessed with repeated measures analysis of variance followed by
      post hoc testing. RESULTS: The number of dermatomes blocked to pinprick, touch,
      and cold was significantly greater with the 1% concentration (2 dermatomes
      greater than the 3% concentration on average, P < 0.05). Similar intensity of
      sensory block to electrical stimulation developed at the hip and knee and was
      unaffected by concentration of 2-chloroprocaine. Similar intensity of motor block
      developed at the quadriceps with both concentrations. CONCLUSIONS: Intensity of
      sensory and motor block from epidural anesthesia with 2-chloroprocaine appears to
      depend primarily on total milligram dose.

PMID- 9197298
TI  - The effect of isoflurane, halothane, sevoflurane, and thiopental/nitrous oxide on
      respiratory system resistance after tracheal intubation.
AB  - BACKGROUND: After tracheal intubation, lung resistance and therefore respiratory
      system resistance (R[rs]) routinely increase, sometimes to the point of clinical
      bronchospasm. Volatile anesthetics generally have been considered to be effective
      bronchodilators, although there are few human data comparing the efficacy of
      available agents. This study compared the bronchodilating efficacy of four
      anesthetic maintenance regimens: 1.1 minimum alveolar concentration (MAC) end
      tidal sevoflurane, isoflurane or halothane, and thiopental/nitrous oxide.
      METHODS: Sixty-six patients underwent tracheal intubation after administration of
      2 microg/kg fentanyl, 5 mg/kg thiopental, and 1 mg/kg succinylcholine. Vecuronium
      or pancuronium (0.1 mg/kg) was then given to ensure paralysis during the rest of
      the study. Postintubation R(rs) was measured using the isovolume technique.
      Maintenance anesthesia was then randomized to thiopental 0.25 mg x kg(-1) x min(
      1) plus 50% nitrous oxide, or 1.1 MAC end-tidal isoflurane, halothane, or
      sevoflurane. The R(rs) was measured after 5 and 10 min of maintenance anesthesia.
      Data were expressed as means +/- SD. RESULTS: Maintenance with thiopental/nitrous
      oxide failed to decrease R(rs), whereas all three volatile anesthetics
      significantly decreased R(rs) at 5 min with little further improvement at 10 min.
      Sevoflurane decreased R(rs) more than either halothane or isoflurane (P < 0.05;
      58 +/- 14% of the postintubation R(rs) vs. 69 +/- 20% and 75 +/- 13%,
      respectively). CONCLUSIONS: After tracheal intubation in persons without asthma,
      sevoflurane decreased R(rs) as much or more than isoflurane or halothane did
      during a 10-min exposure at 1.1 MAC.

PMID- 9197299
TI  - ORG 9487 neuromuscular block at the adductor pollicis and the laryngeal adductor
      muscles in humans.
AB  - BACKGROUND: ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a
      rapid onset of action. This study was designed to determine the neuromuscular
      blocking profile of ORG 9487 at the adductor muscles of the larynx and the
      adductor pollicis. METHODS: In 30 adults, anesthesia was induced with propofol (2
      5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block
      of the laryngeal adductor muscles was evaluated by measuring the pressure changes
      in the cuff of the tracheal tube placed between the vocal cords, and the force of
      the contraction of the adductor pollicis was measured with a force transducer.
      Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses
      of 0.75, 1.5 or 2 mg/kg (n = 10 in each group). RESULTS: Time to peak effect was
      significantly shorter at the vocal cords than at the adductor pollicis muscle (P
      < 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/-
      14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not
      significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/-
      20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P <
      0.001). Maximum block was significantly less intense at the vocal cords than at
      the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/-
      7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg).
      After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5
      min at the vocal cords and the adductor pollicis muscle, respectively, and 75%
      recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min
      at the adductor pollicis muscle. CONCLUSIONS: ORG 9487 has a rapid onset of
      action at the laryngeal adductor and the adductor pollicis muscles. Onset and
      duration of action are faster at the vocal cords than at the adductor pollicis
      muscle. However, the maximum block obtained at the laryngeal muscles was less
      than at the adductor pollicis, regardless of the dose of ORG 9487.

PMID- 9197300
TI  - Pharmacokinetics of rocuronium during the three stages of liver transplantation.
AB  - BACKGROUND: Little is known about the influence of liver transplantation on the
      pharmacokinetics of most anesthetic drugs. The authors determined the
      pharmacokinetics of rocuronium during liver transplantation and examined whether
      variability in pharmacokinetics could explain variability in recovery of
      neuromuscular function. METHODS: Twenty patients undergoing liver transplantation
      were given rocuronium, 600 microg/kg, after induction of anesthesia and again
      after perfusion of the transplanted liver. Plasma was sampled to determine
      rocuronium concentrations. Pharmacokinetic models were fit to rocuronium
      concentrations versus time data using a mixed-effects population approach.
      Various models permitted changes in clearance (Cl) or central compartment volume
      to account for changes in hepatic function and circulatory status during the
      paleohepatic, anhepatic, and neohepatic periods. Time to initial recovery of four
      twitches of the orbicularis oculi was determined. RESULTS: During the
      paleohepatic and anhepatic periods, the typical value of Cl was 2.47 ml x kg(-1)
      x min(-1) and was not influenced by the magnitude of preexisting liver disease
      (as evidenced by prothrombin time, bilirubin, serum albumin, alanine transaminase
      [ALT], and aspartate transaminase [AST]). During the neohepatic period, the
      typical value of Cl varied as a function of the duration of warm ischemia of the
      hepatic allograft and was 2.72 ml x kg(-1) x min(-1) for a patient with an
      average 60-min period of warm ischemia; time to neuromuscular recovery varied as
      a function of Cl. CONCLUSIONS: Despite prolonged hypothermic ischemia, the newly
      transplanted liver eliminates rocuronium as well as the diseased native liver
      (and comparably with historical control values). However, some patients had
      decreased rocuronium Cl during the neohepatic period, apparently a result of
      prolonged graft warm ischemia. The authors' finding of preservation of hepatic
      drug elimination in the hepatic allograft is consistent with limited data for
      other drugs evaluated during anesthesia.

PMID- 9197301
TI  - The cerebral pharmacokinetics of meperidine and alfentanil in conscious sheep.
AB  - BACKGROUND: Different opioids have different delays (hysteresis) between their
      concentrations in blood and their cerebral effects. Possible mechanisms include
      differences in their rate of penetration into the brain and differences in their
      distribution volume in the brain. There have been few in vivo studies of the
      cerebral kinetics of opioids to differentiate these mechanisms. METHODS: The
      cerebral kinetics of meperidine and alfentanil were examined using conscious
      sheep that were fitted with long-term monitoring equipment to measure relative
      changes in cerebral blood flow and opioid concentration gradients across the
      brain through frequent sampling of arterial and sagittal sinus blood. The data
      were compared using hybrid physiologic modeling with membrane-limited (consistent
      with mechanism 1) and flow-limited (consistent with mechanism 2) models of
      cerebral kinetics. RESULTS: Alfentanil had a variable effect on relative cerebral
      blood flow, whereas meperidine induced a transient increase. The arteriovenous
      concentration gradients were small after alfentanil but large after meperidine.
      The flow-limited model gave acceptable descriptions of observed sagittal sinus
      concentrations for alfentanil and meperidine, whereas the membrane-limited model
      collapsed to a flow-limited model. The half-lives of equilibrium between blood
      and brain were 6.3 and 0.8 min for meperidine and alfentanil, respectively:
      CONCLUSIONS: The rate of penetration of both opioids into the brain was rapid and
      not rate-limiting. Large differences in the cerebral distribution volume of
      meperidine and alfentanil accounted for the respective delays in their peak brain
      concentration relative to blood.

PMID- 9197302
TI  - Synergistic inhibition of muscarinic signaling by ketamine stereoisomers and the
      preservative benzethonium chloride.
AB  - BACKGROUND: Ketamine (Ketalar; Parke-Davis, Morris Plains, NJ) has been shown to
      inhibit muscarinic signaling with a median inhibitory concentration (IC50) of 5.7
      microM. Whereas Ketalar is a racemic mixture, recent interest has focused on
      clinical use of the S(+) ketamine isomer, which is three times as potent an
      analgesic as the R(-) isomer yet seems to be associated with fewer psychoactive
      side effects. Therefore, the authors studied the effects of S(+) and R(-)
      ketamine and the preservative benzethonium chloride on muscarinic signaling.
      METHODS: Rat ml muscarinic acetylcholine receptors were expressed recombinantly
      in Xenopus laevis oocytes. Ca2(+)-activated Cl- currents in response to 10(-7) M
      acetyl-beta-methylcholine were determined by two-electrode voltage clamping in
      the presence of various concentrations of ketamine and benzethonium.
      Concentration-inhibition curves were constructed and used for algebraic and
      isobolographic analysis. RESULTS: The IC50. was 125 +/- 33 microM for S(+)
      ketamine, and 91 +/- 19 microM for R(-) ketamine. This difference was not
      statistically significant, indicating that muscarinic inhibition by ketamine is
      not stereoselective. The R(-)/S(+) mixture had an IC50 of 48 +/- 1 microM, and
      thus the stereoisomers interact synergistically. When appropriate concentrations
      of benzethonium were added, an IC50 of 15 +/- 2 microM resulted. CONCLUSIONS: The
      muscarinic inhibitory action of ketamine isomers is not stereoselective. Because
      S(+) ketamine is a significantly more potent analgesic, it should have less
      muscarinic inhibitory action than R(-) ketamine when used in clinically
      equivalent doses. A significant fraction of the muscarinic inhibitory action of
      Ketalar is due to the preservative benzethonium. If reconstituted with a
      different preservative, Ketalar might be a less potent muscarinic antagonist.

PMID- 9197303
TI  - Inhibition of airway constriction by opioids is different down the isolated
      bovine airway.
AB  - BACKGROUND: Opioid agonists attenuate in isolated airways contractile responses
      to electrical field stimulation (EFS), and this attenuation is mediated by opioid
      receptors. Differences exist in the density of muscarinic and beta-adrenergic
      receptors between large and small airways. The authors hypothesized that the
      density of opioid receptors may also be different down the airway. METHODS: The
      effects of three selective opioid agonists (mu, kappa, delta) on EFS-induced
      contractions were compared between isolated bovine sublobar (4- or 5-mm inner
      diameter) and segmental (2- or 3-mm inner diameter) bronchial rings and between
      trachealis strips and bronchial rings. RESULTS: D-Ala2-N-MePhe4-Gly-ol5
      enkephalin (DAMGO; 10(-5) M), a mu-opioid agonist, attenuated EFS-induced
      contractions of isolated sublobar and segmental bronchial rings at low
      stimulating frequencies of 0.5 Hz (P < 0.001), 2 Hz (P < 0.001), and 8 Hz (P <
      0.001), but not at 32 Hz (P = 0.071). The inhibitory effect of DAMGO was
      antagonized by naloxone (10(-5) M) (P = 0.025). The selective kappa-opioid
      agonist U-50488 H (10(-5) m) attenuated EFS-induced contractions at 32 Hz (P =
      0.008) and 8 Hz (P = 0.045), but not at 2-Hz (P = 0.893) or 0.5-Hz (P = 0.145)
      contractions. The inhibitory effects of 10(-5) M U-50488 H were not antagonized
      by the highly selective kappa-antagonist 2,2'-[1,1'-biphenyl] 4,4'-diyl-bis [2
      hydroxy-4,4-dimethyl]-morpholinium (nor-BNI; 10(-5) M; P = 0.216) or naloxone
      (10[-5]) M; P = 0.065). The selective delta-agonist D-penicillamine2-D
      penicillamine5-enkephalin (DPDPE) (10(-5) M) had no inhibitory effects (P =
      0.256). The inhibitory effects of the selective mu-opioid agonist DAMGO were
      smaller (P < 0.001) and those of U-50488 H larger (P < 0.001) in trachealis
      strips compared with bronchial rings. CONCLUSIONS: The attenuation of EFS-induced
      contractions by DAMGO in isolated bovine bronchi was mediated by prejunctional
      opioid receptors. In contrast, the inhibitory effect of U-50488 H was probably
      not mediated by opioid receptors in the bronchi.

PMID- 9197304
TI  - Influences of morphine on the ventilatory response to isocapnic hypoxia.
AB  - BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory
      activity from peripheral chemoreceptors and a depressant effect from within the
      central nervous system. Morphine induces respiratory depression by affecting the
      peripheral and central carbon dioxide chemoreflex loops. There are only few
      reports on its effect on the hypoxic response. Thus the authors assessed the
      effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats
      anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide
      sensitivities of the central and peripheral chemoreflex loops. METHODS: The
      steady-state ventilatory responses to six levels of end-tidal oxygen tension
      (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon
      dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration
      of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an
      exponential function characterized by the hypoxic sensitivity and a shape
      parameter. The hypercapnic ventilatory responses, determined before and after
      administration of morphine hydrochloride, were separated into a slow central and
      a fast peripheral component characterized by a carbon dioxide sensitivity and a
      single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine
      decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110
      ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ
      from control. The ventilatory response to carbon dioxide was displaced to higher
      P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The
      central and peripheral carbon dioxide sensitivities decreased by about 30% (P <
      0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide
      sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105;
      morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at
      hyperoxia but does not depress the steady-state increase in ventilation due to
      hypoxia. The authors speculate that morphine reduces the central depressant
      effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.

PMID- 9197305
TI  - Effects of intracoronary fentanyl on left ventricular mechanoenergetics in the
      excised cross-circulated canine heart.
AB  - BACKGROUND: It is still unclear whether fentanyl directly alters left ventricular
      (LV) contractility and oxygen consumption. This is because of the difficulty in
      defining and evaluating contractility and energy use independently of ventricular
      loading conditions and heart rate in beating whole hearts. METHODS: This study
      was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl
      in six excised cross-circulated canine hearts. The authors used the framework of
      the E(max) (a contractility index)-PVA (systolic pressure-volume area, a measure
      of total mechanical energy)-VO2 (myocardial oxygen consumption per beat)
      relationship practically independent of ventricular loading conditions. The
      authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen
      content difference to calculate E(max), PVA, and VO2. They first obtained the VO2
      PVA relationship for varied LV volumes at control E(max). The authors then
      obtained the VO2-PVA relationship at a constant LV volume, whereas coronary blood
      fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they
      obtained the VO2-PVA relationship for varied LV volumes at the final dose of
      fentanyl. RESULTS: Fentanyl at any concentrations did not significantly change
      E(max), PVA, and VO2 from the control. The linear end-systolic pressure-volume
      relations and their slopes were virtually the same between the control and
      fentanyl volume loading in each heart. Further, either the slope (oxygen cost of
      PVA) or the VO2 intercept (unloaded VO2) of the linear VO2-PVA relationship
      remained unchanged by fentanyl. CONCLUSIONS: These results indicate that
      intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for
      a wide range of its blood concentration.

PMID- 9197306
TI  - Increase of glutamate uptake in astrocytes: a possible mechanism of action of
      volatile anesthetics.
AB  - BACKGROUND: Glutamate is the most ubiquitous excitatory neurotransmitter in the
      vertebrate central nervous system. Astrocytes play an important role in
      terminating glutamatergic neurotransmission by removing released glutamate from
      the synaptic cleft. The authors examined the effects of several anesthetics on
      the glutamate uptake activity of astrocytes. METHODS: Cultured astrocytes from
      hippocampi of rat embryos were incubated with solution containing [3H]glutamate,
      which was pre-equilibrated with 0-4% halothane at 37 degrees C. The uptake
      activity was evaluated as the amount of radioactivity per cell of protein.
      RESULTS: When the reaction solution was equilibrated with 4% halothane, glutamate
      uptake increased to about 165% of the control. The effect of halothane was dose
      dependent, and a significant augmentation (30-50%) of glutamate uptake was
      observed at a range in clinical use concentrations (1-2%). On the other hand, the
      uptake of gamma-aminobutyric acid, an inhibitory transmitter, was hardly affected
      by 1-4% halothane. The effect of halothane on glutamate uptake was also examined
      in neuron-rich culture, and similar augmentation was observed, although the
      extent was less than that in astrocyte culture. Biochemical subcellular fractions
      (i.e., glial plasmalemmal vesicles and synaptosomes) were also examined, however,
      only slight (not significant) increase was detected in the glutamate uptake
      activity. Other volatile anesthetics, such as enflurane, isoflurane, and
      sevoflurane, also enhanced glutamate uptake, whereas the intravenous anesthetics
      ketamine and pentobarbital showed no effect on glutamate uptake. CONCLUSIONS: The
      increase of glutamate uptake by astrocytes in the presence of volatile
      anesthetics potentially attenuates excitatory synaptic transmission in the entire
      central nervous system, a finding that may explain in part the action of volatile
      anesthetics.

PMID- 9197307
TI  - Clearance of mucus from endotracheal tubes during intratracheal pulmonary
      ventilation.
AB  - BACKGROUND: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas
      insufflation in which all gas emerges in a cephalad direction from the tip of a
      reverse-thrust catheter positioned within an endotracheal tube. In vitro
      experiments have shown that this rapid gas flow, with 5 ml/h of normal saline
      added to the gas flow, continuously removes tracheal secretions from within the
      endotracheal tube. The authors evaluated its effectiveness to remove mucus in
      long-term studies in sheep. METHODS: Fourteen healthy sheep were tracheally
      intubated and ventilated for 3 days with ITPV or with volume-controlled
      ventilation. Measurements were made of the total amount of secretions within the
      endotracheal tubes (weight gain), the protein content within the endotracheal
      tubes, and the increase in resistance to constant air flow. The structure of the
      airways was examined grossly and histologically. Three additional sheep were
      ventilated for 24 h with ITPV, and Evans Blue dye was added to the saline to
      assess the distribution of the infused saline. RESULTS: There was significantly
      less mucus in endotracheal tubes of sheep ventilated with ITPV than with
      conventional ventilation, as shown by minimal weight gain (0.70 +/- 0.14 g vs.
      2.44 +/- 0.81 g; P < 0.001), lower protein content (14.09 +/- 10.79 mg vs. 294.99
      +/- 153.06 mg; P < 0.001), and lower resistance to constant air flow (6.15 +/-
      0.54 cm H2O x 1(-1) x s(-1) vs. 15.34 +/- 5.28 cm H2O x 1(-1) x s(-1); P <
      0.001). Results of gross and histological examinations of the tracheas of animals
      in both groups were similar, and the tracheas were well preserved. More than 95%
      of the instilled saline was recovered during ITPV. Only traces of Evans Blue dye
      were found near the tip of the endotracheal tubes. CONCLUSION: Intratracheal
      pulmonary ventilation makes it possible to keep the endotracheal tubes of sheep
      ventilated for 3 days free of mucus without suctioning.

PMID- 9197308
TI  - Endobronchial vasopressin improves survival during cardiopulmonary resuscitation
      in pigs.
AB  - BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary
      resuscitation (CPR) has been shown to be more effective than optimal doses of
      epinephrine. This study evaluated the effect of endobronchial vasopressin during
      CPR. METHODS: After 4 min of untreated ventricular fibrillation and 3 min of CPR,
      21 pigs were randomized to be treated with 0.8 U/kg intravenous vasopressin (n =
      7), 0.8 U/kg endobronchial vasopressin (n = 9), or an endobronchial placebo of
      normal saline (n = 5). Defibrillation was performed 5 min after drug
      administration to attempt return of spontaneous circulation. RESULTS: All animals
      in the intravenous and endobronchial vasopressin group were resuscitated
      successfully, but only two of five animals in the placebo group were. At 2 and 5
      min after drug administration, coronary perfusion pressure in the intravenous and
      endobronchial vasopressin group was significantly higher than in the placebo
      group (50 +/- 10, 34 +/- 5 vs. 16 +/- 6 mmHg, respectively; and 35 +/- 10, 39 +/-
      10 vs. 19 +/- 5 mmHg, respectively; P < 0.05). CONCLUSIONS: Endobronchial
      vasopressin is absorbed during CPR, coronary perfusion pressure is increased
      significantly within a short period, and the chance of successful resuscitation
      is increased in this porcine model of CPR. Endobronchial vasopressin may be an
      alternative for vasopressor administration during CPR, when intravenous access is
      delayed or not available.

PMID- 9197309
TI  - The effects of heparinase 1 and protamine on platelet reactivity.
AB  - BACKGROUND: Protamine is currently the most widely used drug for the reversal of
      heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a
      possible alternative to protamine for the reversal of heparin anticoagulation.
      The authors evaluated the effects of equivalent doses of heparinase and protamine
      on platelet reactivity by measuring agonist-induced P-selectin expression.
      METHODS: After Institutional Review Board (IRB) approval, informed consent was
      obtained from 12 healthy volunteers and 8 patients undergoing surgery requiring
      cardiopulmonary bypass (CPB). Twenty-four ml of blood was obtained from each
      volunteer; 10 ml of blood was obtained from each patient before the CPB, and
      another 10 ml was obtained after CPB. Heparin was neutralized using heparinase or
      protamine. Platelet reactivity was assessed by measuring the expression of P
      selectin after stimulation of platelets with increasing concentrations of a
      thrombin receptor agonist peptide (TRAP). Data were analyzed using analysis of
      variance. P < 0.05 was considered significant. RESULTS: For the healthy
      volunteers, the activated coagulation times (ACTs) of the heparinized samples
      returned to baseline values with heparinase (12.5 U/ml) or protamine (32.5
      microg/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20
      U/ml) or protamine (50 microg/ml). The authors found no difference in the
      expression of P-selectin in samples neutralized with heparinase, but samples
      neutralized with protamine showed a significant decrease in the expression of P
      selectin when compared with heparinized samples. CONCLUSIONS: At dosages that
      reverse the anticoagulant effects of heparin, heparinase has minimal effects on
      platelets, whereas platelet reactivity was markedly inhibited by protamine.

PMID- 9197310
TI  - Laser treatment of endobronchial lesions.

PMID- 9197311
TI  - Perioperative acute renal failure associated with preoperative intake of
      ibuprofen.

PMID- 9197312
TI  - Sevoflurane inhalation induction for emergency cesarean section in a parturient
      with no intravenous access.

PMID- 9197313
TI  - Development of complex regional pain syndrome after a cervical epidural steroid
      injection.

PMID- 9197314
TI  - Perioperative cardiac dysrhythmias: diagnosis and management.

PMID- 9197315
TI  - Laparoscopic cholecystectomy in a patient with a transplanted heart.

PMID- 9197316
TI  - Response to "Iconography in anesthesiology: the importance of society seals in
      the 1920s and 1930s".

PMID- 9197317
TI  - Response to "Iconography in anesthesiology: the importance of society seals in
      the 1920s and 1930s".

PMID- 9197318
TI  - Computed tomography scan-guided neurolytic superior hypogastric block complicated
      by somatic nerve damage in a severely kyphoscoliotic patient.

PMID- 9197319
TI  - Nomenclature for computer-assisted infusion devices.

PMID- 9197321
TI  - Prognostic relevance of cell proliferative rapidity in neoplastic hemo
      lymphopathology.

PMID- 9197320
TI  - The lower limit of autoregulation: time to revise our thinking?

PMID- 9197322
TI  - Proliferative and differentiative potential of thrombopoietin-responsive
      precursors: expression of megakaryocytic and erythroid lineages.
AB  - We investigated changes in proliferative potential and surface markers during
      human megakaryocytic differentiation, using megakaryocytic cells grown by
      thrombopoietin (TPO). Cells grown in response to TPO from CD34+ cord blood cells
      in a liquid culture system expressed CD41b at a frequency of 92% and CD42b at a
      frequency of 80% on day 10, whereas cells expressing other lineage markers
      constituted less than 2.5% of this population. The cultured cells were divided
      into CD41b-/CD42b-, CD41b+/CD42b-, and CD41b+/CD42b+ cells. Comparison of their
      respective proliferative potentials showed that CD41b-/CD42b- cells generated
      megakaryocytic progeny in response to TPO to a lesser extent, but responded to
      the combination of growth factors (GFs) more intensely than CD41b+/CD42b- cells.
      Almost all CD41b+/CD42b+ cells failed to undergo cell division. In the culture
      containing GFs, some CD41b-/CD42b- cells and CD41b+/CD42b- cells gave rise to
      erythroid as well as megakaryocytic progeny. The potential of these cells to
      yield erythroid progeny in response to GFs correlated well with their expression
      of CD34. These results suggest that TPO generates precursors with a potential to
      differentiate into megakaryocytic and erythroid lineages.

PMID- 9197323
TI  - Alterations in the progenitor cell population follow recovery from myeloablative
      therapy and bone marrow transplantation.
AB  - In a previous study we showed that following recovery from bone marrow
      transplantation (BMT), there are persistent derangements in the clonogenic growth
      of hematopoietic progenitors and in the microenvironment. To characterize the
      abnormalities within the precursor cell population, selected BM CD34+ cells from
      15 patients in remission from hematological malignancies who had received
      myeloablative therapy and grafts (eight allogeneic and seven autologous) were
      tested in dose-response studies with recombinant cytokines. Preconditioning for
      transplantation was accomplished with fractionated total body irradiation (fTBI)
      at 12 Gy, cyclophosphamide at 120 mg/kg and fractionated total lymphoid
      irradiation fTLI at 6 Gy. The median mononuclear cell number infused was 0.9 x
      10(8)/kg (SD 0.31). At the time of BMT, the patient's median age was 26 (SD 8.65)
      years and eight were female. Grafts were studied at a median of 37 (SD 48.43)
      months from transplantation. The light density marrow population from the
      patients and controls was monocyte- and T-lymphocyte depleted; CD34+ precursors
      were then selected with immunomagnetic beads (median 90.2 and 92% blasts) and
      cultured in the progenitor cell assay at a cell density of 5 x 10(3) culture with
      incremental concentrations of recombinant human growth factors (rhGFs). BMT
      patients' cultures showed significantly lower colony scores at the lowest
      cytokine concentrations in both erythroid burst-forming units (BFU-Es) and
      erythroid colony forming units (CFU-Es) as well as in myeloid lineages; colony
      forming units-granulocyte macrophage (CFU-GM), and did not improve at the highest
      GF doses. No significant differences in the results were found between the
      autologous and allogeneic marrow sources. We conclude that following BMT, lineage
      restricted progenitors within the CD34+ population are significantly reduced,
      failing to recover even 8 years after transplantation.

PMID- 9197324
TI  - Risk of donor lymphocyte infusions following allogeneic bone marrow
      transplantation.
AB  - Clinical data so far suggest that the resistance to induction of graft-vs.-host
      disease (GVHD) by donor lymphocyte infusions is less prominent in allogeneic bone
      marrow transplant patients than indicated by the limited results of experimental
      studies in animals published many years ago. To confirm this apparent
      discrepancy, graded numbers of donor type splenocytes were given at various
      intervals after bone marrow transplantation to mouse radiation chimeras. The
      results were closely similar to the previously published data, in that the
      chimeras developed a high degree of tolerance, equivalent to 2-3 log protection.
      It was also observed that this tolerance can be broken by prior treatment with a
      lethal dose of cyclophosphamide. It is postulated that the leukemic cells in
      relapsed patients reduce the suppressor cell population that is responsible for
      the resistance to re-induction of GVHD.

PMID- 9197325
TI  - The MS-5 murine stromal cell line and hematopoietic growth factors synergize to
      support the megakaryocytic differentiation of embryonic stem cells.
AB  - Murine embryonic stem (ES) cells are able to differentiate into erythroid, mast,
      and granulomonocytic cells by using appropriate culture conditions. Because we
      were interested in the regulation of tissue-specific expression of the platelet
      glycoprotein IIb gene, we studied the culture conditions, aiming at the
      reproducible production of myeloid cells that included megakaryocytes (MKs) from
      ES cells. We showed that even a complex cocktail of HGFs (stem cell factor,
      interleukin 3, IL6, IL11, granulocyte colony-stimulating factor, and
      erythropoietin) is unable to induce significant myeloid differentiation in day 12
      embryoid bodies. Cocultures of MS-5 stromal cells with ES cells were slightly
      more productive than HGFs. A strong synergistic effect was observed on the growth
      of myeloid colonies and MKs when we used a combination of MS-5 cells plus the HGF
      cocktail. Conditioned medium from MS-5 cells also synergized with the HGF
      cocktail to produce a substantial number of mixed colonies containing MKs. The
      addition of fibroblast growth factor-2 (FGF-2) to the HGF cocktail plus MS-5
      nearly doubled the number of myeloid progenitors, including those with MKs.
      Thrombopoietin (TPO) alone or in any combination with MS-5 or HGFs, did not
      increase the number of MK-containing colonies. However, when TPO was added to the
      HGF cocktail + FGF-2 + MS-5, the number of MKs in liquid cultures and mixed
      colonies increased, and many exhibited a "hairy" appearance resembling
      pseudopodial proplatelet formation. Having defined the culture conditions of ES
      cells that allow the production of all the myeloid lineages including MKs, we
      conclude that the hematopoietic differentiation model of ES cells is especially
      useful for studying the regulation of expression of any gene important in early
      hematopoiesis.

PMID- 9197326
TI  - Norepinephrine protects mice from acute lethal doses of carboplatin.
AB  - We demonstrated in previous studies that adrenergic agents may affect
      hematopoiesis via high- and low-affinity alpha1-adrenoceptors present on bone
      marrow (BM) cells [1-3]. Here we show that norepinephrine administration in mice
      rescued hematopoiesis from the toxic effect of the non-cell cycle specific
      chemotherapeutic agent, carboplatin. Protection of granulocyte/macrophage colony
      forming units (GM-CFUs) was already apparent only a few hours after carboplatin
      and norepinephrine administration. On day 3, hematopoietic rescue was reflected
      by higher leukocyte and platelet counts. At its most effective dose (3 mg/kg,
      subcutaneously injected), norepinephrine protected 77% of the mice previously
      injected intravenously with 200 mg/kg of carboplatin (LD 100: 170 mg/kg).
      Simultaneous administration of the alpha1-adrenoceptor antagonist prazosin
      reduced the percentage of surviving mice to 30%, indicating that alpha1
      adrenoceptors mediated most of the norepinephrine-induced hematopoietic rescue.
      Consistently, prazosin administration also reduced blood counts and GM-CFUs. In
      vitro, norepinephrine (1 microM) rescued GM-CFUs in BM cells, although this
      effect was counteracted by low concentrations (0.1-10 nM) of prazosin. Our
      findings indicate a previously undescribed novel mechanism of hematopoietic
      regulation and may find application in preventing the myeloablative effect of
      anticancer treatments.

PMID- 9197327
TI  - Hematopoietic precursor cell exhaustion is a cause of proliferative defect in
      primitive hematopoietic stem cells (PHSC) after chemotherapy.
AB  - The authors used the competitive repopulation assay and simple statistical
      analyses to estimate concentrations of primitive hematopoietic stem cells (PHSCs)
      in the marrow of mice after chemotherapy. Single doses of cyclophosphamide (CTX)
      from 80 to 200 mg/kg were administered to C57B16/J mice. Other treatment groups
      included mice given multiple doses of CTX at the lowest dose of 80 mg/kg; mice
      given four weekly doses of vincristine (VCR) or vinblastine (VBL); mice given two
      biweekly doses of bleomycin; mice receiving cytosine arabinoside (ARA)
      administered intraperitoneally thrice daily or as a continuous infusion by Alzet
      pump for 3 days; and controls given no drug. The lowest dose of CTX (80 mg/kg),
      given once or repeatedly, spared PHSC numbers and function. The functional
      capacity of PHSCs declined significantly once doses of CTX exceeded 100 mg/kg.
      Decreases in PHSC function were usually associated with reductions in PHSC
      numbers; repopulating units, which include all repopulating cells, were similarly
      reduced. At the highest dose (33 mg/kg for 3 days), ARA caused a decline in
      marrow repopulating function. Drugs associated with mild clinical
      myelosuppression, such as VCR and VBI, did not significantly affect the
      repopulating ability of PHSCs, although VCR caused drastic declines in PHSC
      numbers. The marrow reconstitutive defects clinically-observed after chemotherapy
      may be caused partly by depletion of the PHSC pool.

PMID- 9197328
TI  - Immunological classification of chronic myeloid leukemia distinguishes chronic
      phase, imminent blastic transformation, and acute lymphoblastic leukemia.
AB  - The clinical course of chronic myeloid leukemia (CML) is highly variable and
      therefore it is difficult to predict the duration of the chronic phase. We
      studied the immunological expression of maturation patterns in 62 cases of CML
      (30 cases in clinical/cytological blast crisis (BC), 32 cases in
      clinical/cytological chronic phase (CP) by means of a double marker enzyme immuno
      assay (DM-EIA). Immunological findings were supplemented by Southern blots using
      Ig-JH-, TCRbeta- and bcr-probes. Patients in BC (n = 30) expressed high
      proportions of CD10, CD20, CD33, CD34 and low degrees of a mature myeloid marker
      (CD15). Myeloid BC bone marrow (BM) cells showed a high degree of coexpression of
      unusual, lineage restricted markers: 25% of CD15-positive cells also expressed
      markers like CD10, CD20 or CD34. In contrast, BM cells in lymphoid BC did not
      show this coexpression. In CP two groups were distinguished immunologically:
      concordant cases which were immunologically normal (n = 14) and discordant cases
      (n = 18) which showed increased proportions of unusual, lineage restricted
      markers and double labelled cells (e.g. CD15/CD34). The latter group developed
      clinical BC earlier during further follow up (p = 0.009). Cases of lymphoid BC (n
      = 11)--in contrast to acute lymphoblastic leukemia (ALL) patients (n = 21)--did
      not show coexpression of CD15/CD10, CD20, CD34. These data show that blast clones
      can be detected in CML-CP by characteristic immunological maturation defects
      several months before the clinical onset of BC. Moreover, the lymphoid "blasts"
      of CML-BC represent a relatively differentiated lymphoid population of cells
      which can be distinguished from ALL by their lack of coexpression of unusual,
      lineage restricted markers.

PMID- 9197329
TI  - Effects of vesnarinone on the bone marrow stromal cell-dependent proliferation
      and differentiation of HL60 cells in vitro.
AB  - It has been reported that vesnarinone, a new inotropic agent used in the
      treatment of cardiac failure, causes agranulocytosis as a side effect. To study
      the mechanisms by which this complication occurs, vesnarinone was introduced into
      a coculture system of HL60 and bone marrow (BM) stromal cells, in which HL60
      cells were able to differentiate into mature granulocytes with no inducible
      exogenous factors added to the culture. When HL60 cells were cocultured with the
      human BM-derived stromal cell line LP101, HL60 cells were induced to
      differentiate into mature granulocytes, and expression of the mature granulocyte
      macrophage surface antigen, CD11b was increased. Conditioned medium (CM) obtained
      from LP101 cells also showed the capacity to induce the maturation of HL60 cells,
      in a dose- and time-dependent manner. The differentiation of HL60 cells induced
      by CM was also determined by morphological analysis, expression of
      myeloperoxidase, and a nitroblue tetrazolium (NBT) reduction test. When HL60
      cells were cocultured with LP101 in the presence of vesnarinone, the CD11b
      expression was greatly suppressed. CM obtained from vesnarinone-treated LP101
      (ves-CM) lost the capacity to induce the differentiation of HL60 cells, at a
      concentration of 1 microg/mL of vesnarinone. Vesnarinone itself did not affect
      the proliferation of HL60 cells. Furthermore, the addition of vesnarinone or ves
      CM to HL60 cultures incubated with CM did not alter the induction of CD11b
      expression, suggesting that vesnarinone has no effect on HL60 cells, but that it
      inhibits stromal cells from producing soluble factor(s) required for the
      differentiation of HL60 cells to mature granulocytes. All these findings indicate
      that vesnarinone causes the hematopoietic disorder agranulocytosis, via
      impairment of stromal function.

PMID- 9197330
TI  - High-dose granulocyte-colony stimulating factor (G-CSF) in vitro induces the
      growth of high proliferative potential colony forming cells (HPP-CFC) in patients
      undergoing blood stem cell mobilization.
AB  - We evaluated the role of high-dose granulocyte colony stimulating factor (G-CSF)
      in vitro, in inducing the generation of high-proliferative potential colony
      forming cells (HPP-CFC), from either mononuclear cells or purified CD34+ cells.
      Both normal controls and patients undergoing peripheral blood stem cell (PBSC)
      mobilization and transplantation were studied. In serum-driven agar cultures, G
      CSF stimulated the proliferation of HPP-CFC in a dose dependent manner (r =
      0.92). The number of HPP-CFC was four-fold greater in mobilized patients than in
      normal controls. Purified CD34+ cells yielded 11-fold more colonies than
      mononuclear cells. HPP-CFC from mobilized patients showed replating capacity,
      giving rise to secondary colonies of more mature appearance. In serum-free
      cultures, the effect of G-CSF appeared to be mediated by synergistic interaction
      with stem cell factor. Our results suggest that G-CSF stimulates primitive
      hematopoietic cells that are detectable in increased amounts in patients
      receiving mobilization therapy. Therefore, determination of G-CSF induced HPP-CFC
      could be a useful tool in the evaluation of mobilization strategies.

PMID- 9197331
TI  - Cryptic and regulatory epitopes in CD13/aminopeptidase N.
AB  - CD13/Aminopeptidase N (APN) is a ubiquitous cell surface enzyme thought to be
      involved in downregulation of regulatory peptide signals, in binding viruses, and
      possibly in tumor invasion. Functional aspects of CD13/APN were probed using two
      monoclonal antibodies (F23 and MY7) to two distinct epitopes on the protein and
      using substrates and inhibitors of the enzyme. F23 was capable of completely
      blocking, and MY7 was capable of partially blocking, the binding of substrate to
      APN and the enzymatic activity of APN. The number of epitopes on APN was
      quantitated by flow cytometry and by radiobinding with Scatchard analysis. There
      were approximately 20,000 F23 epitopes per HL60 cell, whereas there were about
      10,000 MY7 epitopes per cell. After binding of F23 or natural peptide substrates,
      the number of MY7 epitopes increased to become equimolar with F23 epitopes,
      showing a conformational change in CD13/APN structure that reveals MY7 epitopes.
      Mild proteinase treatment also revealed the hidden epitopes and equalized epitope
      numbers. The presence of cryptic epitopes may explain the different effects of
      these antibodies on substrate binding and enzymatic activity. Competition
      analysis identified the substrate binding site as involving the zinc binding
      domain of the enzyme. The substrates blocked F23 epitopes (zinc binding domain of
      the enzyme) and MY7 epitopes, whereas inhibitors blocked only the F23 epitopes,
      and downregulated MY7 epitopes. A dimeric structure for CD13/APN, in its native,
      membrane-bound state was directly demonstrated by cross-linking with Bis
      (sulfosuccinimidyl) suberate and gel electrophoresis. Despite the conformational
      changes that increased or decreased MY7 epitopes in CD13/APN after substrate or
      inhibitor binding, neither substrates nor inhibitors caused alterations in the
      ratio of homodimers to monomers. This suggests that APN undergoes intramolecular
      conformational changes rather than gross separation of protomers during its
      regulation. A model for the conformational regulation of APN is proposed.

PMID- 9197332
TI  - Cell cycle kinetic studies in 68 patients with myelodysplastic syndromes
      following intravenous iodo- and/or bromodeoxyuridine.
AB  - Sixty-eight patients with myelodysplastic syndromes (MDS) received sequential
      infusions of iodo- and/or bromodeoxyuridine for cell kinetic analysis. Bone
      marrow biopsy sections were treated by appropriate antibodies and a labeling
      index (LI), duration of S-phase (Ts), and total cell cycle time (Tc) of myeloid
      cells were determined. The mean LI was 28.4%, Ts was 11.8 hours and Tc was 40.7
      hours. The %LI decreased as the disease evolved from refractory anemia toward
      transformation to acute leukemia (p = 0.04). Double-labeling of biopsy sections
      for apoptosis and proliferation showed that 30-90% of S-phase cells in MDS
      patients were simultaneously apoptotic or "antonymous." We conclude that MDS are
      highly proliferative disorders in which the ineffective hematopoiesis is probably
      the result of excessive apoptosis rather than slow proliferation.

PMID- 9197334
TI  - Early transplantation to a normal microenvironment prevents the development of
      Steel hematopoietic stem cell defects.
AB  - Our previous results showed that hematopoietic stem cells from 16-week-old
      Sl/Sl(d) mice are not as competitive as congenic +/+ control stem cells. Possible
      explanations for these findings are that the Steel stem cells are either
      inherently defective or lose competitive ability by residence in an environment
      lacking membrane-bound Steel factor. In the present report, any long-term effects
      of the Steel microenvironment were eradicated by transferring neonatal
      Sl(d)/Sl(d) marrow and spleen cells into an irradiated but otherwise normal adult
      hematopoietic microenvironment. Host cells were completely replaced by donor
      cells within 6 weeks. Eight months after transplantation, the Sl(d)/Sl(d) and
      similarly treated +/+ littermate control cells from the primary recipient marrow
      were competed against genetically marked normal cells in an irradiated secondary
      host. The Steel cells were as competitive as the control cells demonstrating that
      Steel stem cells are not inherently defective. Results suggest that the stem
      cells, when retained in the mutant environs into adulthood, are either reduced in
      number or phenotypically altered by lack of the membrane-bound Steel factor.

PMID- 9197333
TI  - Expression of B cell markers on SR-4987 cells derived from murine bone marrow
      stroma.
AB  - The murine cell line SR-4987 was originated in our laboratory from adherent cells
      of a long term bone marrow culture. SR-4987 cells do not express p21-ras and c
      fms products on membrane whereas secrete M-CSF, evidence a fibroblast-like
      morphology and are vimentine positive. This line shows a very poor "in vitro"
      agar clonogenicity which is not modulated by the addition of different cytokines
      and growth factors (M-CSF, GM-CSF, G-CSF, IL-3, IL-7, alpha-TNF, PDGF, and EGF).
      On the contrary, a dramatic increase in clonogenicity is observed in the presence
      of bFGF. The RT-PCR investigation evidences the mRNA encoding for bFGF, IL-7, GM
      CSF, and SCF (c-kit ligand). The analysis of CD antigen expression on SR-4987
      cell membrane indicates a phenotype (CD5+, CD44+, 45R(B220)+, sIg+, 5'
      nucleotidase+) that is consistent with a B cell feature. Our observations suggest
      that exogenous bFGF might represent an appropriate stimulus for inducing the SR
      4987 cells proliferation also in the absence of cell-substrate anchorage.
      Further, they indicate that SR-4987 cells could represent a particular
      differentiation stage in which characters of "stromal cell" and "B cell" are
      coexpressed in agreement with the hypothesis of a common stromal-hematopoietic
      differentiation.

PMID- 9197335
TI  - National Heart, Lung, and Blood Institute (NHLBI) workshop on the importance of
      minor histocompatibility antigens in marrow transplantation. September 16-17,
      1996; Bethesda, Maryland.

PMID- 9197336
TI  - Current management of the neonatal abstinence syndrome: a critical analysis of
      the evidence.
AB  - OBJECTIVE: To systematically and critically analyse and summarise the published
      evidence for the rational choice of pharmacologic treatment of the neonatal
      abstinence syndrome (NAS), a frequently observed condition in neonates born to
      mothers who are dependent on physically addicting drugs. DESIGN: Studies
      comparing different pharmacological agents for the treatment of NAS were
      identified utilising MEDLINE and additionally the references cited in pertinent
      articles. The identified studies were critically analysed regarding their study
      designs and outcome measures. The reported data for the comparative efficacy of
      the drugs were summarised and evaluated. RESULTS: Fourteen studies were
      identified, most of them comparing treatment of NAS with phenobarbital, paregoric
      or diazepam. However, none of these studies was conducted in a double-blind
      fashion. Frequently, treatment allocations were not properly randomised. Prenatal
      drug exposure varied and was often not sufficiently verified. Outcome measures
      and their evaluations differed widely. Due to the different study objectives and
      flaws in study design, a combined analysis of the published data in the form of a
      meta-analysis was not deemed possible. When attempting to compare efficacy,
      diazepam appears to be less efficacious in treating NAS than phenobarbital or
      paregoric. The relative efficacy of paregoric and phenobarbital appears to depend
      upon the antenatal exposure of the neonate and on the outcome measure of the
      study. Only two studies evaluate the efficacy of pure opioids, none of them in
      direct comparison to paregoric. It remains questionable whether paregoric, which
      contains the central stimulant camphor and a large amount of alcohol, should be
      the opioid of choice for the treatment of NAS. CONCLUSION: Most published studies
      were conducted prior to the development of clinical epidemiology and modern study
      design and thus yielded only very limited comparative data on the benefits of
      different treatment protocols. There is very little evidence regarding the
      efficacy of different pharmacological therapy regimens to treat NAS. More studies
      are required to produce the evidence needed to allow a rational choice between
      treatment modalities of NAS and thus to ensure optimal care of the neonates
      suffering from this condition.

PMID- 9197337
TI  - Cephalocaudal progression of jaundice in newborns admitted to neonatal intensive
      care units.
AB  - The influence of several clinical factors on the cephalocaudal progression of
      neonatal jaundice was investigated in 377 newborns admitted to the neonatal
      intensive care unit for various reasons. Multiple regression analysis showed
      that, beyond the relationship to the plasma bilirubin concentration, the
      cephalocaudal color gradient was significantly, negatively related to gestational
      and postnatal age. Furthermore, the cephalocaudal progression of jaundice seemed
      more extended in females compared to males. The results are in agreement with a
      theory explaining that the cephalocaudal color gradient is due to conformational
      changes in the newly formed bilirubin albumin complexes.

PMID- 9197338
TI  - Urinary nitrite excretion in low birth weight neonates with systemic inflammatory
      response syndrome.
AB  - Increased nitric oxide (NO) levels are thought to play an important role in the
      pathophysiology of the systemic inflammatory response syndrome (SIRS) which is
      caused by disseminated vascular endothelial damage. Clinical studies have shown
      that urinary nitrite (NO2-) and nitrate (NO3-) excretions can be utilized as
      indexes of NO formation. The SIRS and NO relationship was investigated in 15
      neonates with SIRS, gestational age 32.5 +/- 4.4 weeks and weight 1,737 +/- 753
      g. The control group comprised 18 neonates with a gestational age of 32.8 +/- 3.5
      weeks and a weight of 1,778 +/- 538 g. There was no significant difference in
      birth weights and gestational ages between the two groups (p > 0.05 and p >
      0.05). The urinary nitrite levels obtained in the subjects were normalized for
      urinary creatinine concentrations. The mean urinary nitrite levels in the control
      group neonates were found to be 4.22 +/- 1.8 micromol/mmol creatinine on the 1st
      day, 4.09 +/- 2.28 on the 2nd, 3.62 +/- 1.6 on the 3rd, and 4.01 +/- 1.12
      micromol/mmol creatinine on the 7th day. There were no statistically significant
      differences between these levels (p > 0.05). We determined urinary levels of
      nitrite in neonates in the study group within the first 24 h of SIRS symptoms and
      found these levels (18.35 +/- 11.16 micromol nitrite/mmol creatinine) to be
      elevated as compared with those of the control subjects on the 7th day of life (p
      < 0.0005). In conclusion, urinary nitrite excretion is significantly elevated in
      neonates with SIRS due to septic events, and these results suggest that NO might
      play a part in SIRS.

PMID- 9197340
TI  - Testicular arginine vasopressin in the developing rat: a possible physiological
      role.
AB  - Testicular immunoreactive arginine vasopressin (irAVP) has been shown to inhibit
      testosterone production by the Leydig cell in vitro. We studied pre- and
      postpubertal rats and the results are in agreement with the notion that such
      inhibition might occur in vivo and, therefore, could have physiological
      significance. Testicular irAVP and serum testosterone levels were measured in 14
      , 21-, 28-, 35-, 42-, and 70-day-old rats. The testicular irAVP concentration was
      lowest in early prepubertal rats, increased significantly to the highest level at
      35 days, then decreased at 42 days, and plateaued at 70 days of age. A pubertal
      increase in serum testosterone was observed at 42 days when AVP was decreasing.
      Thus, an inverse relationship was observed at the onset of pubertal maturation.
      These parameters were also measured in 3 groups of rats 1 week after
      hemicastration which was performed at the ages of 28, 35 and 70 days. In the 28
      day-old rats there was a significant decrease in irAVP 1 week later, in contrast
      to the intact animal, whereas hemicastration performed at 35 and 70 days of age
      had no impact on irAVP. Our data suggest that the role of AVP may be
      physiologically relevant during the peripubertal period of testicular maturation
      in the rat.

PMID- 9197339
TI  - Differences in movement quality at term among preterm and term infants.
AB  - Significant differences in movement quality at term are reported in high-risk
      preterm (n = 18), low-risk preterm (n = 21) and term (n = 20) infants. Movement
      quality was judged using 2-minute video collection of general movements; three
      parameters of movement quality could be assessed reliably in a semiquantitative
      way: fluency, spatiotemporal variability and sequencing. The parameters fluency
      and variability correlated highly with each other (r = 0.47-0.99) while their
      correlations with sequencing were less (r = 0.42-0.67). Significant differences
      on all quality parameters were noted between term, low-risk preterm and high-risk
      preterm infants (p < 0.001-0.05). The findings indicate a significant impact of
      prematurity per se and brain damage on movement quality.

PMID- 9197341
TI  - Cerebral oxygen delivery is reduced during the acidaemia associated with
      prolonged hypoxaemia in the immature ovine fetus.
AB  - Our aim was to determine the effects of 12 h of hypoxaemia on cerebral blood flow
      (CBF) and cerebral O2 delivery in ovine fetuses at 0.6 gestation. During fetal
      hypoxaemia, induced by reduced uterine blood flow, fetal SaO2 and PaO2 were
      reduced (p < 0.01) from control values of 77.0 +/- 1.6% and 27.3 +/- 1.0 mm Hg,
      respectively, to 28.4 +/- 3.4% and 15.6 +/- 0.6 mm Hg; fetal pHa decreased from
      control values of 7.37 +/- 0.01 to 7.20 +/- 0.02 at 3 h, but returned to control
      values before 12 h. CBF (ml/min/100 g) was 2.0- to 2.6-fold higher (p < 0.01)
      than control values during hypoxaemia, but only 1.7-fold higher (p < 0.01) at 3 h
      when pHa was lowest. Cerebral O2 delivery (ml/min/100 g) was lower (p < 0.01)
      than control values of 3.15 +/- 0.29 at 1.5h (2.09 +/- 0.36) and 3h (1.84 +/-
      0.22) of hypoxaemia and higher 1 h after hypoxaemia had ceased (3.81 +/- 0.22, p
      < 0.01). We conclude that the ovine fetus at 0.6 gestation is unable to sustain
      increased CBF and hence maintain cerebral O2 delivery during the first 6 h of
      hypoxaemia, a time which coincides with acidaemia; in contrast, at 6 and 12 h of
      hypoxaemia, when pHa was normal, cerebral O2 delivery was similar to control
      values. Reduced cerebral O2 delivery during the early, acidaemic, stages of
      hypoxaemia may lead to impaired neural development.

PMID- 9197342
TI  - Secretion in milk and transplacental transfer of two iodized oils, Lipiodol UF
      and Oriodol, in rabbits.
AB  - Many countries in the world are inhabited by populations suffering from iodine
      deficiency. These populations are affected by serious diseases directly related
      to iodine deficiency. Iodized oil (Lipiodol UF or Oriodol) is routinely used
      orally or intramuscularly to treat these populations, including pregnant women.
      The experiments of the present study in gravid or lactating rabbits show that
      there is transplacental transfer of iodine and secretion of iodine in milk after
      administration of iodized oil and consequently an accumulation of iodine in the
      thyroid glands of the mother, the fetus and the neonate. The advantages of
      treating pregnant women with iodized oil in the populations concerned is thus
      confirmed. The oral route can be substituted by the intramuscular route.

PMID- 9197343
TI  - Treatment of surgically induced acute liver failure by transplantation of
      conditionally immortalized hepatocytes.
AB  - The shortage of human livers available for hepatocyte isolation limits its
      clinical application. The availability of cloned, conditionally immortalized
      hepatocytes that could be grown in culture but would lose their transformed
      phenotype and provide metabolic support upon transplantation would greatly
      facilitate the treatment of acute liver failure. Toward this goal, we transduced
      isolated Lewis rat hepatocytes using a replication-defective recombinant
      retrovirus capable of transferring a gene encoding a thermolabile mutant simian
      virus 40 T antigen (SV40ts). The cloned, immortalized hepatocytes proliferate at
      33 degrees C. At the nonpermissive temperatures (37-39 degrees C), they stop
      growing and exhibit characteristics of differentiated hepatocytes. These cells
      did not produce tumors when transplanted in mice with severe combined
      immunodeficiency disease or in syngeneic rats. To induce acute liver failure,
      Lewis rats were subjected to 90% hepatectomy (Hpx) and given 5% oral dextrose.
      All rats that did not undergo hepatocyte transplantation died within 96 hr. Fifty
      percent of rats that received intrasplenic injection of 10 x 10(6) primary Lewis
      rat hepatocytes (G2, n=6) or 10 x 10(6) SV40ts-conditionally immortalized (SV40ts
      ci) hepatocytes (G3, n=8) 1 day before 90% hepatectomy survived, whereas 80% of
      rats that received an intraperitoneal injection of 200 x 10(6) primary Lewis rat
      hepatocytes (G4, n=10) or 200 x 10(6) SV40ts-ci hepatocytes (G5, n=10) on the day
      of hepatectomy survived. Survival after intraperitoneal injection of a cellular
      homogenate of 200 x 10(6) primary Lewis rat (G7, n=9) or SV40ts-ci hepatocytes
      (G8, n=10) on the day of Hpx was 33% and 40%, respectively, whereas survival
      after intraperitoneal injection of 200 x 10(6) Lewis rat bone marrow cells (G6,
      n=7) was 29%. Thus, transplanted, conditionally immortalized hepatocytes can be
      as effective as primary hepatocytes in supporting life during acute liver
      insufficiency. This work represents the first step in developing an hepatocyte
      cell line that would partially alleviate the organ-donor shortage and could be of
      potential clinical value.

PMID- 9197344
TI  - Effect of calcium antagonists on rat liver during extended cold preservation
      reperfusion.
AB  - BACKGROUND: Nisoldipine, a calcium antagonist, has been reported to improve the
      quality of grafted rat livers. We thus assessed the protective effect of two
      calcium antagonists, nisoldipine and nickel, during extended cold ischemia
      reperfusion. METHODS: Rat livers were isolated and perfused before or after 24 hr
      of cold ischemia in University of Wisconsin solution (4 degrees C) with or
      without nisoldipine or nickel. Sinusoidal endothelial cell and hepatocyte
      functions were measured by hyaluronic acid and taurocholate elimination,
      respectively. RESULTS: Similar alterations in hepatocyte and sinusoidal cell
      functions were found in all groups after cold ischemia with or without calcium
      antagonists. In a second set of experiments, liver transplantation was performed
      in two groups of rats with livers stored under identical conditions with or
      without nisoldipine. Seven of 12 animals (62.5%) in both groups survived for over
      10 days after 24-hr preservation in University of Wisconsin solution. Survival
      rates were similar in both groups. CONCLUSIONS: Calcium antagonists do not appear
      to have a direct protective effect on sinusoidal endothelial cell and hepatocyte
      functions, nor on the overall liver preservation after extended cold preservation
      reperfusion.

PMID- 9197345
TI  - Effect of graft preservation and IgM depletion on guinea pig to rat cardiac
      xenograft survival.
AB  - BACKGROUND: Heterotopic guinea pig (GP) cardiac xenografts (XG) are hyperacutely
      rejected within minutes when transplanted into rats. METHODS: In this GP to rat
      cardiac XG model, we studied the effect on graft survival of a short cold
      preservation time (1 hr at 4 degrees C) in the presence or absence of rat anti-GP
      IgM preformed antibodies. The complete depletion of circulating IgM was obtained
      by two intraperitoneal injections of anti-rat IgM monoclonal antibody (MARM-4) on
      preoperative days -3 and -1. RESULTS: When the GP cardiac XG was cold preserved
      for 1 hr before transplantation, the mean graft survival time (MST) was 13.5+/
      2.8 min, whereas without previous cold preservation, the MST was significantly
      prolonged to 51.5+/-12.3 min (P<0.001). Interestingly, the complete depletion of
      preformed circulating IgM before grafting significantly prolonged the MST of a
      cold-preserved XG to 37.1+/-11.3 min in comparison with a nondepleted recipient
      of a cold-preserved XG (P<0.02), but did not prolong the graft survival of a XG
      that was not cold preserved (42.5+/-14.1 min). To assess the effect of cold
      preservation and/or ischemia reperfusion, we intravenously injected a superoxide
      dismutase mimetic (EUK-134) just before transplantation of a cold-preserved XG.
      This antioxidant regimen improved the MST from 13.5+/-2.8 min to 35.3+/-7.3 min
      (P<0.001). These results clearly suggested that either preservation lesions or
      preformed IgM are capable of accelerating the loss of the cardiac graft function,
      but also that the presence of preformed IgM seems to be especially deleterious
      when the cardiac XG has previously been ischemically injured. Analyzing the
      histological data, we also observed that the prompt cessation of cardiac function
      seen in cold-preserved grafts was uniformly associated with massive interstitial
      hemorrhage, thereby suggesting a particular susceptibility of the GP cardiac XG
      to cold preservation. To assess the effect of preservation on the GP cardiac
      function in a nonimmunological model, we performed syngeneic GP cardiac grafts
      and found that 1 hr of cold preservation provoked massive interstitial hemorrhage
      capable of promptly inducing the cessation of the heartbeat. CONCLUSIONS:
      Overall, this study demonstrated that both ischemic lesions and immunological
      processes might induce the cessation of cardiac graft function in the GP to rat
      model and this cessation of graft function is probably often misinterpreted as a
      XG rejection only.

PMID- 9197346
TI  - Significant increase of Kuppfer cells associated with loss of Na+,K+-ATPase
      activity in rat hepatic allograft rejection.
AB  - BACKGROUND: Cholestasis is a complication that occurs during the rejection of
      liver transplants. The aim of this study was to investigate the association of
      activated Kupffer cells (KCs) and Na+,K+-ATPase activity for taurocholate
      cotransport and bile canalicular (BC) Mg++-ATPase activity for hepatobiliary
      excretion in rat liver allograft. METHODS: Quantitative analyses of KC number and
      size in relationship to enzyme activity of Na+,K+-ATPase and of BC Mg++-ATPase
      were conducted in rejected liver after allogenic transplantation and after
      prevention of rejection using cyclosporine. RESULTS: The animals were examined on
      the 10th postoperative day. In the rejection group, the number of KCs
      significantly increased more than fourfold in comparison with the number of KCs
      in the control livers. Some KCs were found in the sinusoids, but the majority
      were located in the space of Disse. Na+,K+-ATPase activity vanished from the
      basolateral plasma membrane, whereas BC Mg++-ATPase activity was restored in the
      apical domain. With immunosuppression, KCs showed the same behavior as in the
      control group, and activity of both ATPases was observed as strong electron-dense
      precipitates in basolateral and apical plasma membrane domains. CONCLUSIONS: In
      this study, we demonstrate that activated KCs migrate into the donor liver and
      release cytokines, which leads to the loss of Na+,K+-ATPase activity in the
      rejection group. BC Mg++-ATPase activity was not influenced by these mediators of
      activated macrophages. Since Na+,K+-ATPase is the cotransporter for hepatocyte
      taurocholate uptake, these data may contribute to understanding the mechanisms
      for cholestasis during hepatic allograft rejection.

PMID- 9197347
TI  - Strain variation in susceptibility to monoclonal antibody-induced transplantation
      tolerance.
AB  - BACKGROUND: We have reproducibly induced specific tolerance to multiple minor
      histocompatibility antigens with nondepleting anti-CD4 and -CD8 monoclonal
      antibodies. The tolerance induced is effective for the lifetime of the host. We
      have tested this therapy in a number of mouse strain combinations to further
      understand the mechanisms. METHODS: Various mouse strains were grafted with
      allogeneic tail skin with and without nondepleting CD4- and CD8-specific
      monoclonal antibody therapy. The grafts were monitored daily for signs of
      rejection. RESULTS: Whereas the CBA/Ca (H2k) strain can be made tolerant to skin
      grafts that are mismatched at multiple minor histocompatibility antigens
      indefinitely, using the same protocol, long-term survival of similarly mismatched
      grafts on the HW80 (B6 congenic for BALB H1) mouse strain is limited to around 8
      weeks. Interestingly, the B10.BR strain, which is also of the H2k haplotype, is
      also not readily tolerized. In addition, an F1 between the CBA/Ca and the
      resistant B10.BR strains is B10.BR-like in its susceptibility to tolerance
      induction. Susceptibility to such antibody-dependent tolerance induction is not
      related to immunogenicity because grafts mismatched at only a single minor
      antigen also do not reproducibly survive beyond 8 weeks when grafted onto HW80
      mice in the presence of the antibody therapy. CONCLUSIONS: The data strongly
      suggest that the B6/B10 genetic background confers a level of resistance to CD4-
      and CD8-specific monoclonal antibody-dependent tolerance induction.

PMID- 9197348
TI  - Cholestatic effects of cyclosporine in the rat.
AB  - BACKGROUND: Previous studies of cyclosporine-induced cholestasis were flawed by
      confounders encountered in human studies and discrepancies in acute animal
      experiments. Even the cyclosporine vehicle, polyoxyethylated castor oil
      (Cremophor EL), had been implicated in cholestasis. The purpose of this study was
      to investigate how cyclosporine affects bile salt kinetics and biliary lipid
      secretion in a rat model under steady state conditions. METHODS: Three groups of
      male Lewis rats (n=10) were given daily subcutaneous injections of either
      cyclosporine (CsA; 10 mg/kg body weight), Cremophor, or NaCl (control) for 1
      week. Twenty-four-hour bile collection was performed 18 hr after the last
      injection. The first hour's output measured bile flow and organic bile solute
      secretion rates. Bile salt pool size and basal synthesis were determined with the
      washout technique. RESULTS: CsA significantly reduced basal bile flow and bile
      salt secretion by 25%. Bile salt synthesis was suppressed 45% (CsA: 3.50+/-0.8
      micromol/g liver/24 hr vs. control: 6.31+/-1.17 micromol/g liver/24 hr; P<0.05),
      which resulted in a 28% reduction in the bile salt pool size (CsA: 16.9+/-1.9
      micromol/g liver vs. control: 23.6+/-2.0 micromol/g liver; P<0.05). Bile salt
      independent flow was significantly suppressed (29%), whereas bile salt-dependent
      flow was only modestly reduced. Biliary phospholipid output decreased 23% (CsA:
      11.7+/-0.8 nmol/min/g liver vs. control 15.2+/-1.1 nmol/min/g liver; P<0.05), but
      cholesterol secretion was unaltered, resulting in a 29% increase in the
      cholesterol saturation index (CsA: 0.40+/-0.03 vs. control 0.31+/-0.02; P<0.05).
      Cremophor had no significant effects on bile secretion or bile salt kinetics.
      CONCLUSIONS: CsA induces cholestasis by decreasing both bile flow and bile salt
      secretion. Its suppression of bile salt synthesis reduces the bile salt pool
      size. The drug inhibits bile salt and phospholipid secretion without a
      corresponding change in cholesterol secretion and thus elevates cholesterol
      saturation in bile, a potential risk for gallstone formation.

PMID- 9197349
TI  - Evaluation of pancreas transplant needle biopsy: reproducibility and revision of
      histologic grading system.
AB  - BACKGROUND: Tissue samples for the diagnosis of pancreatic allograft rejection
      are now obtained routinely through the application of the percutaneous needle
      biopsy technique. The availability of biopsy material (89% adequate for diagnosis
      in our setting) presents a challenge for pathologists who are asked to provide a
      fast and accurate diagnosis of rejection and its severity, while at the same time
      being able to differentiate rejection from other causes of graft dysfunction.
      METHODS: To differentiate rejection from other pathologic processes, 26
      histologic features were assessed in 92 biopsies performed for confirmation of
      clinical diagnosis of rejection and the results were compared with 31 protocol
      biopsies, 12 allograft pancreatectomies with non-rejection pathology, and 30
      native pancreas resections with various disease processes. RESULTS: Based on
      these comparisons, a constellation of findings relating to the vascular, septal,
      and acinar inflammation was identified for the diagnosis of rejection.
      Application of these features led us to revise our scheme for grading rejection
      (ranging from 0-normal to V-severe rejection) to include the categories of
      "inflammation of undetermined significance" and "minimal rejection." The scheme
      was used by five pathologist to grade 20 biopsies independently of any clinical
      data and the interobserver level of agreement was highly significant (kappa=0.83,
      P<0.0001). This grading scheme was applied blindly to all (183) biopsies from 77
      patients with 6-52 months of follow-up. The correlation of the highest degree of
      rejection on each patient and ultimate graft loss (0% for grades 0-I, 11.5% for
      grade II, 17.3% for grade III, 37.5% for grade IV, and 100% for grade V) was
      highly statistically significant (P<0.002). The fraction of grafts lost due to
      pure immunologic causes increased proportionally to the grade of rejection (0,
      50, 66, and 100% for grades II, III, IV, and V, respectively). CONCLUSIONS: This
      study provides strong support for the proposed pancreas rejection grading scheme
      and confirms its potential for practical use.

PMID- 9197350
TI  - Blood transfusions in liver recipients: a conundrum or a clear benefit in the
      cyclosporine/tacrolimus era?
AB  - Blood transfusions are common in patients with end-stage liver disease (ESLD),
      and their effects on sensitization, rejection, and liver graft survival are not
      well known. These effects were examined in 121 recipients of primary liver
      grafts, surviving > or = 30 days. Ninety-six (79%) patients received transfusions
      before transplantation. Transfusion recipients had significantly fewer severe or
      recurrent rejection episodes (18%), compared with patients who did not receive
      transfusions (42%, P=0.006), if the first transfusion was > or = 90 days before
      the transplant. Patients with alcoholic ESLD (n=49) had significantly fewer
      severe rejection episodes when compared with the nonalcoholic (n=72) patients
      (12% vs. 35%, P=0.004). The transfusion benefit was, however, more apparent and
      significant in the nonalcoholic (26% vs. 56% in nontransfused, P=0.02) than among
      the alcoholic recipients (6% vs. 25%, P=0.1). This finding is, most likely, due
      to a combination of a higher rate of severe rejection and the statistical power
      of the larger number of recipients in the nonalcoholic group. This finding is
      further corroborated by a multivariate analysis in which blood transfusions
      retained their benefit (P<0.05) independent of recipient's age and diagnosis.
      Graft and patient survival were not significantly different in the transfused
      versus nontransfused groups. Transfusion recipients had a higher panel antibody
      (11.4+/-23.4 vs. 2.7+/-8.1, P<0.02) but no increased risk of a positive
      crossmatch. In liver recipients, blood transfusions diminish the risk of
      rejection independent of recipient's age and the cause of ESLD.

PMID- 9197351
TI  - The Nordic multicenter double-blind randomized controlled trial of prophylactic
      ursodeoxycholic acid in liver transplant patients.
AB  - BACKGROUND: Prophylactic treatment with ursodeoxycholic acid (UDCA) has been
      reported to reduce the incidence of acute rejection after liver transplantation
      compared with historical controls. We investigated this in a prospective,
      randomized, placebo-controlled multicenter study. METHODS: Fifty-four liver
      transplant patients were allocated to the UDCA treatment group (15 mg/kg/day),
      and 48 patients were allocated to the placebo group. Trial medicine was started
      on the first postoperative day and was given for 3 months. Follow-up was for 12
      months. Treatment was stratified for adults with chronic liver disease (n=77),
      adults with acute liver failure (n=10), and children (n=15). RESULTS: The
      frequency of patients with acute rejection was 65% in the UDCA treatment group
      and 68% in the placebo group. The frequency of steroid-resistant rejection was
      similar in both groups. The probability of acute rejection, analyzed according to
      the intention-to-treat policy with Kaplan-Meier analysis, was similar in both
      treatment groups. No significant differences were found in patient survival and
      graft survival probabilities. For the biochemical markers of cholestasis, only
      gamma-glutamyltransferase was significantly improved after 2 months of UDCA
      treatment. CONCLUSIONS: The initial optimistic report of a beneficial effect of
      prophylactic treatment with UDCA on acute rejection after liver transplantation
      was not confirmed in this controlled study.

PMID- 9197352
TI  - Cytomegalovirus disease is associated with increased cost and hospital length of
      stay among orthotopic liver transplant recipients.
AB  - Cytomegalovirus (CMV) is a cause of considerable morbidity and mortality among
      orthotopic liver transplant (OLT) recipients. To study the impact of CMV on cost
      and hospital length of stay in this population, we undertook an analysis of a
      cohort of OLT recipients from four transplant centers in Boston who participated
      in a CMV prophylaxis trial. First posttransplant year hospital length of stay
      (including the hospital stay after transplantation and readmissions within 1 year
      after transplantation) was available for all 141 patients included in the study.
      In a multiple linear regression model bacteremia (P=0.0001), CMV disease
      (P=0.0007), abdominal reexploration (excluding retransplantation) (P=0.0070),
      recipient age < or = 16 years (P=0.0352), and the number of units of blood
      products (red blood cells, platelets, or fresh frozen plasma) administered during
      transplantation (P=0.0523) were shown to be independently associated with longer
      first posttransplant year hospital length of stay. Cost data for in-hospital care
      for the year beginning with admission for liver transplantation were available
      for 66 OLT recipients. Using a multiple linear regression model, development of
      CMV disease (P=0.0001), the number of units of blood products administered during
      transplantation (P=0.0001), bacteremia (P=0.0002), decreased pretransplant renal
      function (estimated by creatinine clearance) (P=0.0109), and need for
      retransplantation (P=0.0619) were shown to be independently associated with
      higher cost. These data strongly suggest that CMV disease has a direct impact on
      cost and hospital length of stay in liver transplantation.

PMID- 9197353
TI  - Cardiac allograft vasculopathy: IgM antibody responses to donor-specific vascular
      endothelium.
AB  - We have previously demonstrated that heightened cell-mediated immunity to donor
      specific endothelium was associated with an increased incidence of cardiac
      allograft vasculopathy (CAV) at 1 year postcardiac transplantation. We further
      demonstrated that the development of IgG antibody directed to donor-specific HLA
      antigens was extremely uncommon and, furthermore, had no relationship to the
      development of CAV. Subsequent studies have demonstrated a correlation between
      IgM antibody directed against endothelial cell antigens and the development of
      CAV. Accordingly, recipient serum obtained between 6 and 8 weeks (early) and 1
      year (late) after transplantation were reacted with recombinant human interferon
      (rhIFN)-gamma pretreated donor-specific human aortic endothelial cells (HAECs) in
      10 recipients with and 10 recipients without CAV at 1 year after transplantation.
      HAEC IgM binding was assessed by flow cytometry and complement fixation and HAEC
      lysis was measured using standard chromium release assays. Seven of 10 and 5 of
      10 patients with CAV had IgM detected by flow at early and late time points,
      respectively (14+/-2 and 16+/-5 mean channel shift), whereas 5 of 10 and 6 of 10
      patients without CAV had IgM detected by flow at early and late time points,
      respectively (15+/-4 and 14+/-3 mean channel shift). This finding was not
      different between groups. Despite between 50% and 70% of all patients having
      detectable IgM binding to ECs, no patient's serum was cytotoxic to its donor
      specific HAECs. We conclude that IgM antibody to endothelial cells is common (at
      low titers) after transplantation. This antibody is not cytotoxic and in this
      study provided no discrimination between those with and without chronic
      rejection.

PMID- 9197355
TI  - Impact of acute rejection and early allograft function on renal allograft
      survival.
AB  - Both acute rejection and the function of a renal allograft early after
      transplantation correlate with long-term graft survival. In this study we
      assessed the relationship between these two factors in 843 adult recipients of
      first cadaveric renal grafts, transplanted at a single institution and followed
      for a minimum of 3.5 years. Patients were divided into four groups according to
      (1) history of acute rejection (AR) during the first 6 months after
      transplantation, and (2) concentration of serum creatinine at 6 months after
      transplantation (SCr(6mo) < or > or = 2 mg/dl). Death censored allograft survival
      was not significantly different among patients without AR and with low SCr(6mo)
      (group 1, n=376), patients without AR but with an elevated SCr(6mo) (group 2,
      n=117), and patients with AR but low SCr(6mo) (group 3, n=185). In contrast,
      graft survival was significantly worse in patients with AR and an elevated
      SCr(6mo) (group 4, n=165) compared with patients in the other three groups (Cox,
      P<0.0001). The elevated SCr(6mo) in group 4 patients was not necessarily the
      consequence of AR, as 32% of patients in group 4 had a SCr at 10 days after
      transplantation (SCr(10d)), before they had AR, that was equal to or higher than
      the SCr(6mo). Based on this observation we investigated the implications of the
      SCr(10d) concentration for graft prognosis. The SCr(10d) correlated weakly with
      graft survival (Cox, P=0.05). However, an elevated SCr(10d) correlated with other
      potential risk factors for graft survival including: Older donors (P<0.0001),
      male recipients (P<0.0001), and heavier recipients (P<0.0001, all by multivariate
      regression); and posttransplant factors such as, increasing numbers of AR
      (P<0.0001), higher posttransplant blood pressure (P<0.0001), and lower doses of
      cyclosporine (P<0.0001, all by multivariate regression). In conclusion, graft
      dysfunction predicts poor graft survival only when associated with AR. Similarly,
      AR predicts a poor renal allograft survival only when associated with graft
      dysfunction. The SCr(10d) is an indicator of risk factors from both the donor and
      recipient, and an elevated SCr(10d) predicts a higher risk of acquiring
      additional risk factors early after transplantation.

PMID- 9197354
TI  - Effects of pentoxifylline on renal function and blood pressure in cardiac
      transplant recipients: a randomized trial.
AB  - BACKGROUND: The current success of cardiac transplantation is in part
      attributable to the development of effective immunosuppressive agents such as
      cyclosporine. However, concern remains regarding the potential for cyclosporine
      induced nephrotoxicity. Animal studies and early reports of renal protective
      effects of pentoxifylline in bone marrow transplant recipients prompted a
      randomized trial in cardiac transplant recipients. METHODS: Twenty-nine patients
      were randomized to receive pentoxifylline 400 mg p.o. t.i.d. or matching placebo
      for 1 year after cardiac transplantation. Renal function was assessed
      preoperatively and at 1, 6, and 12 months postoperatively. Glomerular filtration
      rate and renal plasma flow were measured with iothalamate and para
      aminohippurate, respectively. Serum creatinine was also measured. Ambulatory
      blood pressure monitoring after withdrawal of antihypertensives for 3 days was
      performed 12 months postoperatively. RESULTS: Twenty-seven patients completed the
      study. Glomerular filtration rate rose between 1 and 6 months after
      transplantation, presumably due to the reduction in goal cyclosporine level in
      that period, and then fell modestly between 6 and 12 months, presumably due to
      ongoing nephrotoxic effects of cyclosporine. No difference in glomerular
      filtration rate or creatinine was seen between pentoxifylline and placebo groups
      at any interval. Renal plasma flow increased modestly between baseline and 6
      months in the pentoxifylline group, but not in the placebo group, and then fell
      between 6 and 12 months. Serum creatinine increased between baseline and 6 months
      in both groups, apparently due to increased body weight. Results of 18-hr
      ambulatory blood pressure monitoring obtained 1 year after transplantation was
      not different between groups. CONCLUSIONS: Renal function declines only modestly
      in the first year after cardiac transplantation. Pentoxifylline did not attenuate
      this process and had no effect on blood pressure. The modest decline in renal
      function may be related to current immunosuppressive strategies.

PMID- 9197356
TI  - Postoperative production of anti-donor antibody and chronic rejection in renal
      transplantation.
AB  - To study the relevance of anti-donor antibody (ADA) to chronic rejection in
      kidney transplantation, we retrospectively examined the long-term kinetics of ADA
      by flow cytometric analysis. Among 537 recipients who underwent living-donor
      kidney transplantation between 1986 and 1994, 29 patients with chronic rejection
      (CR group) and 33 patients with stable graft function (ST group) were randomly
      selected for analysis. Patient serum taken 1 or 2 days before transplantation,
      serum taken 1 month after transplantation, and the most current serum were
      analyzed for the presence of ADA to donor T and B cells. In the CR group, IgG
      antibody to donor B cells of the most current serum was positive in 25 of 29
      patients, whereas it was positive in only 5 patients in the ST group P<0.001. The
      mean fluorescent intensity of the antibody was also significantly higher in the
      CR group than that in ST group P<0.01. In contrast, IgG antibody to donor T cells
      of the most current serum was positive in only five patients in the CR group. No
      significant difference was observed in the pretransplant and 1-month
      posttransplant sera between the CR and ST groups. We conclude that the
      posttransplant production of IgG antibody to donor B cells seemed to be highly
      relevant to chronic rejection.

PMID- 9197358
TI  - Recurrence of type I membranoproliferative glomerulonephritis after renal
      transplantation: analysis of the incidence, risk factors, and impact on graft
      survival.
AB  - BACKGROUND: The information in the medical literature on the incidence of
      recurrence of type I membranoproliferative glomerulonephritis (MPGN) after renal
      transplantation and its impact on graft survival is limited because most data are
      derived from case reports or from studies involving a small number of patients.
      METHODS: We analyzed the data from our transplant center. Among 1097 adult
      patients receiving their first allograft between 1977 and 1994, we identified 32
      patients with type I MPGN. RESULTS: A recurrence was detected in 9 of the 27
      recipients of a first cadaveric graft (33%). The cumulative incidence reached 48%
      at 4 years after transplantation when patients with graft failure from other
      causes were censored. All patients with recurrent MPGN had clinically significant
      proteinuria (>1 g/24 hr) that was first observed at a median time of 20 months
      (range, 1.5-42 months) after transplantation. Graft survival was significantly
      worse in patients with recurrence as compared with patients without recurrence.
      Mean duration of graft survival after the diagnosis of recurrence was 40 months.
      We could not detect any clinical characteristics of patients or donors that were
      associated with recurrent disease. However, an increased risk of recurrence was
      observed in patients with the HLA haplotype B8DR3. Four patients received an HLA
      identical graft from a living related donor. Recurrence occurred in three
      patients (75%), with ensuing graft loss in two. The only patient with a
      haploidentical living related graft did not have a recurrence. Five patients with
      a recurrence in the first graft received a second transplant. Recurrence was
      observed in four of these patients (80%). CONCLUSIONS: Type I MPGN recurred after
      renal transplantation in half of the patients. The incidence may be even higher
      in recipients of an identical living related donor graft and in patients
      receiving a second transplant after having experienced a recurrence in their
      first graft. Recurrence of type I MPGN has a detrimental effect on graft
      survival.

PMID- 9197357
TI  - Risk factors for delayed graft function in cadaveric kidney transplantation: a
      prospective study of renal function and graft survival after preservation with
      University of Wisconsin solution in multi-organ donors. European Multicenter
      Study Group.
AB  - BACKGROUND: Delayed graft function (DGF) remains an important complication in
      renal transplantation. In this multicenter study, we investigated the influence
      of donor and recipient factors on the occurrence of DGF and DGF's effect on long
      term graft survival. METHODS: A total of 547 transplanted kidney allografts,
      retrieved from multi-organ donors, were analyzed, and results were compared with
      literature on kidney-only donors. RESULTS: Median follow-up of patients without
      graft failure was 3.4 years. Twenty-four percent of the recipients developed DGF.
      In univariate analysis, the following factors significantly increased the
      incidence of DGF: (a) among the donor factors, mean creatinine level >120
      micromol/L and prolonged cold ischemia time (CIT); and (b) among the recipient
      factors, previous transplant(s), no intraoperative use of mannitol, poor quality
      of reperfusion, absence of intraoperative diuresis, and pretransplant anuria or
      oliguria. After stepwise logistic regression, donor age, CIT, recipient's number
      of previous transplants, and intraoperative diuresis proved to be of independent
      prognostic value for the occurrence of DGF. Overall graft survival was 91%, 87%,
      and 72% at 3 months, 1 year, and 4 years after transplantation, respectively. In
      case of DGF, graft survival was approximately 10% lower when compared with cases
      with immediate graft function (P<0.001). No difference in incidence of DGF was
      found between grafts of multi-organ donors and kidney-only donors. CONCLUSIONS:
      DGF results in an approximately 10% higher rate of graft failure. DGF incidence
      can be reduced by the administration of mannitol during transplantation, which
      minimizes CIT and optimizes donor management. Grafts from multi-organ donors and
      kidney-only donors appear to be of equal quality.

PMID- 9197359
TI  - Membranous glomerulonephritis associated with hepatitis C virus infection in
      renal transplant patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection has been described in association
      with various types of glomerular diseases, usually type I membranoproliferative
      glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this
      article, we describe the first series of MGN exhibited in renal transplant
      patients and associated with HCV infection. METHODS: From January 1980 to
      December 1994, 2045 kidney transplantations were performed in our renal
      transplant units. A retrospective analysis demonstrated an overall 20% prevalence
      of HCV virus-positive patients; 409 transplanted patients were HCV positive
      (ELISA and RIBA). RESULTS: Fifteen patients developed an allograft MGN (3.66%) 24
      months after renal transplantation. MGN appeared in the form of significant
      proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy
      demonstrated a thickening of the capillary wall, subepithelial electron-dense
      deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten
      cases were considered de novo, two cases were considered recurrent MGN, and three
      cases were considered undetermined because the primary renal disease was chronic
      glomerulonephritis. All patients showed negative antinuclear antibodies and
      cryoglobulins, normal complement, and negative rheumatoid factors. During follow
      up (an average of 2 years), 12 patients developed a progressive worsening of
      renal function, with increased serum creatinine and persistent proteinuria; 8 of
      the 12 patients returned to dialysis. Of the remaining three cases, two patients
      showed partial remission of nephrotic syndrome after high doses of steroids, and
      one patient persisted with stable renal function and proteinuria (<2 g/24 h.).
      CONCLUSIONS: In summary, HCV is preferentially associated with MGN in renal
      transplant patients, rather than with membranoproliferative glomerulonephritis as
      in the normal adult population. MGN associated with HCV infection has a similar
      clinical picture and outcome to posttransplant idiopathic de novo MGN, with
      persistent massive proteinuria and progressive deterioration of renal function.

PMID- 9197360
TI  - Clinical and economic impact of flow cytometry crossmatching in primary cadaveric
      kidney and simultaneous pancreas-kidney transplant recipients.
AB  - We retrospectively compared the clinical and financial impact of a final cross
      match by T cell flow cytometry (FXM) versus conventional complement-dependent
      cytotoxicity (CXM) in consecutive primary cadaveric kidney (K) and primary
      simultaneous cadaveric pancreas-kidney (SPK) transplant recipients. Mean follow
      up was 14 months for both the K (range, 5-22 months) and SPK (range, 5-22 months)
      recipients. There were no instances of a positive CXM result if the FXM result
      was negative. However, 18 of the 102 (18%) K recipients and 11 of the 66 (17%)
      SPK recipients were FXM positive, CXM negative, but no grafts lost to hyperacute
      rejection in this group. In addition, patient survival, graft survival, incidence
      of acute rejection, and kidney and pancreas function (immediate and late) were
      not different in the FXM-positive versus the FXM-negative groups. Charges for the
      CXM and FXM methods were compared over a 6-month period. During that period, the
      FXM charges averaged $583 less per recipient than the CXM charges (58% reduction
      in charges), and the time required to perform the FXM method was 50% of that
      required for the CXM method. These results demonstrate that a clinical pathway
      for primary transplantation that utilizes the FXM rather than the CXM final cross
      match is clinically safe, with no adverse effect on posttransplant outcome,
      reduces organ preservation time by shortening the waiting period for the final
      cross-match results, and significantly reduces the tissue typing charges.
      However, about 9% of all primary K and SPK recipients will be FXM positive, CXM
      negative on final cross-match and will be unnecessarily denied a transplant. In
      this study, we describe a method to identify these patients so that they can be
      tested by traditional CXM to avoid being denied access to donor organs.

PMID- 9197361
TI  - Early establishment of chimerism in the B and T lymphoid lineages after
      transplantation of allogeneic mobilized blood cells in leukemic patients.
AB  - BACKGROUND: The use of allogeneic recombinant human granulocyte colony
      stimulating factor (rhG-CSF)-mobilized blood cells was recently evaluated in
      patients with malignancies. METHODS: Ten patients with leukemia were transplanted
      with allogeneic blood cells from HLA-identical sex-mismatched siblings; blood
      cells were mobilized with recombinant rhG-CSF. Up to 6 months after
      transplantation, blood and bone marrow samples were obtained from the recipient
      and analyzed for the presence of donor cells, using fluorescence in situ
      hybridization with specific probes hybridizing to sex chromosomes. RESULTS:
      Analysis of blood and bone marrow smears demonstrated a complete chimera, as
      early as day 15 after transplantation. Furthermore, marrow and blood CD4+, CD8+,
      CD19+, and CD34+ cells were sorted using direct immunofluorescence and flow
      cytometry: fluorescence in situ hybridization analysis on sorted cells
      demonstrated that most progenitors and most cells in the T- and B-cell lineages
      were of donor origin as early as day 15 after transplantation. CONCLUSIONS:
      Together with recently reported results, this study demonstrates that allogeneic
      rhG-CSF-mobilized blood cells contain primitive hematopoietic progenitors that
      can repopulate all lymphoid and myeloid lineages. Establishment of chimerism
      seems to be quick and stable, including the T- and B-cell lineages. Although
      establishment of chimerism in mitogen-responsive T cells is readily assayable
      with conventional cytogenetics, our study provides additional insight on the
      reconstitution of the B lineage and T-cell subsets after allogeneic
      transplantation in patients with leukemia.

PMID- 9197362
TI  - Angiogenesis in cultured and cryopreserved pancreatic islet grafts.
AB  - BACKGROUND: The ability of rat pancreatic islets to revascularize after
      transplantation was examined via in vitro and in vivo imaging of the
      microvasculature using laser scanning confocal microscopy (LSCM). METHODS:
      Cultured or cryoprocessed islets were transplanted at the renal subcapsular site
      in rats. At various time intervals after transplantation, three-dimensional
      imaging of the graft was performed by LSCM. In vitro studies were conducted via
      microvascular corrosion casting of the grafted kidney in situations where it was
      difficult to obtain in vivo confocal data due to surgical complications. The
      vascular morphology of the islet grafts was evaluated quantitatively via digital
      image analysis algorithms to determine the morphology of the neovascular ingrowth
      and the rate of revascularization. RESULTS: In cultured islet grafts, the
      initiation of angiogenesis was observed within 1 week, characterized by the
      presence of capillary sprouts, tortuous vessels, and blood vessels with blind
      ends. The revascularization of the graft was typically completed within 2 weeks
      and could be distinguished as a network of completely perfused blood vessels
      consisting of intertwining capillaries, with surrounding arterioles and venules.
      The angiogenesis process in cryopreserved islet grafts required a longer time
      period to initiate (approximately 2 weeks), and the revascularization was
      completed in 1 week after the initiation. CONCLUSIONS: These results successfully
      demonstrate the potential of the described in vivo and in vitro LSCM techniques
      to measure the angiogenesis process in pancreatic islet grafts.

PMID- 9197363
TI  - Prevention of cyclosporine-induced nephrotoxicity with dietary glycine.
AB  - BACKGROUND: The nonessential amino acid glycine has been used previously to
      prevent hypoxic and ischemic injury to kidney tissue in vitro. Furthermore, it
      was recently shown that glycine prevents activation of macrophages and
      neutrophils in vitro. Because there is some evidence that the immunosuppressant
      cyclosporine causes nephrotoxicity through a hypoxia-reoxygenation mechanism that
      could involve infiltration and activation of macrophages and neutrophils, we
      hypothesized that dietary glycine could prevent this injury. METHODS: Rats were
      fed a diet containing glycine (5%) or a control diet for 3 days before
      cyclosporine treatment. To produce nephrotoxicity, cyclosporine (25 mg/kg daily
      by gavage) was administered for 28 days while animals were maintained on glycine
      or control diets. Serum creatinine, urea, glomerular filtration rates, and kidney
      histology were evaluated in different treatment groups. RESULTS: All rats gained
      weight; however, overall weight gain in the cyclosporine, glycine, and
      cyclosporine+glycine groups was significantly less by about 40% compared with the
      control group. Diet consumption was not statistically different between the
      groups. As expected, cyclosporine caused kidney damage in the rats fed control
      diet, reflected in significantly elevated serum urea and creatinine. In addition,
      cyclosporine treatment decreased glomerular filtration rate by nearly 70%, caused
      proximal tubular dilation and necrosis as well as increased macrophage and
      neutrophil infiltration into the kidney. Dietary glycine prevented or minimized
      kidney damage due to cyclosporine in all parameters studied nearly completely.
      Furthermore, feeding glycine for up to 1 month had no detrimental effect on
      kidney function. CONCLUSIONS: Dietary glycine is a safe and effective treatment
      to reduce the nephrotoxicity of cyclosporine.

PMID- 9197364
TI  - Fractionated dosing of cyclophosphamide for establishing long-lasting skin
      allograft survival, stable mixed chimerism, and intrathymic clonal deletion in
      mice primed with allogeneic spleen cells.
AB  - BACKGROUND: Injection of allo-spleen cells (SC) followed by a single dose of
      cyclophosphamide (CP) can induce tolerance of tumor and/or skin allografts in
      mice. To minimize the damage caused by CP, fractionation of CP that can establish
      long-lasting skin graft survival, stable mixed chimerism, and intrathymic clonal
      deletion in the host was investigated in the present study. METHODS: Allo-SC
      (10(8)) were given intravenously on day 0. CP at 200 mg/kg was given
      intraperitoneally on day 2 in a single dose (CP 200x1 group). CP at 100, 66, 50,
      40, and 33 mg/kg was given daily from day 1 through days 2, 3, 4, 5 and 6,
      respectively, in the fractionated doses (CP 100x2, 66x3, 50x4, 40x5, and 33x6
      groups; total dose=200 mg/kg). Allografting was performed on day 14. RESULTS: In
      a fully allogeneic combination of C57BL/6 (H2b)-->AKR (H2k, Mls-1a), an EL-4
      tumor (H2b) was specifically accepted to kill the AKR mice in all of the SC+CP
      200x1, 100x2, 66x3, 50x4, 40x5, and 33x6 groups (n=6), but C57BL/6 skin graft
      survival was not prolonged in any of the tumor-tolerant groups. In an H2
      identical combination of AKR-->C3H (H2k, Mls-1b), AKR skin graft survival was
      prolonged remarkably (80-90 days) in the SC+CP 200x1, 100x2, and 66x3 groups (n=5
      11), but was prolonged moderately (20-60 days) in the SC+CP 50x4 and 40x5 groups.
      In both of the SC+CP 200x1 and 66x3 groups in the AKR-->C3H combination, mixed
      chimerism was maintained for as long as 100 days after tolerance induction in
      both the spleen and thymus, associated with intrathymic clonal deletion of
      Vbeta6+ T cells. The decreases in leukocyte count, hemoglobin level, spleen
      weight, SC count, and body weight were significantly smaller in the SC+CP 66x3
      group than in the SC+CP 200x1 group. CONCLUSIONS: Fractionated CP is effective in
      ameliorating the compromised state induced by a single dose of CP. To induce a
      long-lasting skin allograft survival associated with stable mixed chimerism and
      intrathymic clonal deletion in an H2-identical combination, 200 mg/kg of CP can
      be divided into three or fewer fractions.

PMID- 9197366
TI  - En bloc pancreas and kidney transplantation in a patient with limited vascular
      access.
AB  - We report a successful en bloc pancreas and kidney transplantation on a type I
      diabetic patient with advanced peripheral arterial calcific disease, who had
      frequent life-threatening episodes of hypoglycemia. The en bloc double organ,
      created by joining the graft renal artery to the arterial Y graft of the
      pancreas, was implanted to the proximal left common iliac artery, which was the
      only site available for an arterial anastomosis. Under appropriate circumstances,
      this procedure would be an option for potential combined pancreas-kidney
      transplant recipients with severe calcific arterial disease.

PMID- 9197365
TI  - Removal of xenoreactive human anti-pig antibodies by absorption on recombinant
      mucin-containing glycoproteins carrying the Gal alpha1,3Gal epitope.
AB  - BACKGROUND: The hyperacute rejection caused by preformed natural antibodies in
      the recipient species reacting with donor species endothelial antigens is one of
      the major obstacles preventing routine use of clinical xenotransplantation. Based
      on the known structure and biosynthetic pathway of the major porcine xenoantigen,
      Gal alpha1,3Gal, we developed a novel strategy aimed at specific removal of
      human, natural anti-pig antibodies. METHODS: Cotransfection of COS cells with
      expression plasmids encoding a secreted mucin/immunoglobulin chimera and the
      porcine alpha1,3-galactosyltransferase facilitated simple immunoaffinity
      purification of a highly Gal alpha1,3Gal-substituted mucin/immunoglobulin fusion
      protein from transfected cell supernatants. RESULTS: Cotransfection of COS cells
      resulted in a mucin/Ig concentration in the supernatants ranging from 150 to 200
      ng/ml. Approximately 300 ng of mucin/Ig chimeras absorbed onto 50 microl of
      packed anti-mouse IgG agarose beads could completely remove cytotoxic human anti
      pig antibodies from 1 ml of human AB serum, as estimated in porcine endothelial
      cell cytotoxicity assays. Purified human IgG, IgM, and IgA all bound porcine
      endothelium, but only IgG and IgM were cytotoxic in the presence of rabbit
      complement. When the cytotoxicity of human IgG at 8 mg/ml and IgM at 1 mg/ml was
      completely removed by absorption on the mucin/Ig chimera, the binding to porcine
      endothelium was only partly reduced. Antibodies mediating antibody-dependent
      cellular cytotoxicity against porcine endothelium were also absorbed, indicating
      the importance of Gal alpha1,3Gal epitopes for this effect. CONCLUSIONS: We
      describe the construction and production of a new and effective Gal alpha1,3Gal
      substituted, mucin domain-containing absorber that can be used in a pretransplant
      extracorporeal immunoabsorption setting to remove anti-pig antibodies involved in
      antibody-dependent, complement- and cell-mediated cytotoxicity of pig endothelial
      cells.

PMID- 9197367
TI  - Lethal graft-versus-host disease after simultaneous kidney-pancreas
      transplantation.
AB  - BACKGROUND: This case report is the first documentation of the occurrence and
      potential source of lethal graft-versus-host disease (GVHD) after simultaneous
      kidney-pancreas transplantation. The patient was a 27-year-old African-American
      male who received an ABO-compatible, five HLA antigen-mismatched kidney-pancreas
      transplant from a 17-year-old African-American female donor, who died after
      childbirth. METHODS: Preoperative crossmatches using lymphocytotoxicity and flow
      cytometry were negative. The patient received four blood transfusions within 10
      days of transplantation. Immunosuppression consisted of OKT3 induction, and then
      cyclosporine, azathioprine, and corticosteroids. RESULTS: On postoperative day
      (POD) 9, the patient became febrile, and leukocytopenia and pancytopenia
      developed. Immunosuppression was reduced and granulocyte colony-stimulating
      factor was begun. Cultures were negative, interleukin 6 and interleukin 8 levels
      were elevated, and a cutaneous rash appeared on POD 18. A skin biopsy
      demonstrated dermatitis with focal epidermal necrosis consistent with GVHD. In an
      attempt to identify the source of GVHD, variable-number tandem repeat analysis
      fingerprinting was performed with DNA from donor splenocytes, from the skin
      biopsy, as well as from the patient's buccal mucosa. The skin biopsy showed a
      mixed variable-number tandem repeat analysis type containing DNA fragments
      matching the recipient and donor. Blood donors were excluded as a source because
      they were serologically different from the organ donor. The patient developed
      liver abnormalities and died from multiorgan failure on POD 22. CONCLUSIONS: We
      speculate that carryover of passenger donor lymphocytes within the transplanted
      organ were responsible for GVHD. Furthermore, donor traits such as sexual
      mismatching, African-American race, and alloimmune status may be important
      potential risk factors for GVHD.

PMID- 9197368
TI  - Steroid withdrawal in mycophenolate mofetil-treated renal allograft recipients.
AB  - BACKGROUND: Acute rejection is an inherent risk of the withdrawal of steroids in
      renal allograft recipients. Mycophenolate mofetil is a potent immunosuppressant
      that, when given with cyclosporine (CsA), reduces the incidence of acute
      rejection and may facilitate discontinuation of steroids without increasing the
      risk of rejection. METHODS: In an open pilot study, steroids were withdrawn from
      26 adult cadaveric kidney transplant recipients. Corticosteroids were
      discontinued between 4 and 30 (mean 17) months after transplantation, and steroid
      free follow-up ranged from 7 to 18 (mean 10) months. RESULTS: Mean CsA doses, CsA
      blood levels, and serum creatinine at the time of steroid withdrawal and at last
      patient visit after cessation of steroids were 4.2+/-1.2 mg/kg/day and 3+/-0.8
      mg/kg/day (P<0.001), 170+/-53 ng/ml and 113+/-34 ng/ml (P<0.001), and 133+/-36
      microM/L and 130+/-37 microM/L (NS), respectively. No rejection episodes occurred
      after steroid withdrawal. CONCLUSIONS: This open study shows that corticosteroids
      can be safely and successfully withdrawn from renal allograft recipients
      receiving CsA and mycophenolate mofetil.

PMID- 9197369
TI  - Treatment of posttransplant lymphoproliferative disease in the central nervous
      system of a lung transplant recipient using allogeneic leukocytes.
AB  - Posttransplant Epstein-Barr virus-related lymphoproliferative disease (PT-LPD) is
      a common and often fatal complication following solid organ and hematopoietic
      stem cell transplantation. PT-LPD following solid organ transplantation generally
      occurs in B cells of recipient origin in contrast to PT-LPD in marrow transplant
      recipients, which is exclusively of donor origin. The efficacy of adoptive
      immunotherapy using donor leukocytes to treat PT-LPD in bone marrow transplant
      recipients has recently been reported. Because PT-LPD in solid organ transplant
      recipients is generally of recipient origin, the potential application of
      adoptive immunotherapy of PT-LPD in solid organ recipients obligates the use of
      either autologous or allogeneic HLA identical leukocytes, with the attendant risk
      of organ rejection if cells mismatched with the transplanted organ are used.
      Nonirradiated allogeneic mononuclear cells from an Epstein-Barr virus (EBV)
      seropositive, HLA-identical normal sibling were used to treat a monoclonal EBV
      lymphoma of recipient origin in the central nervous system of a child who had
      undergone an HLA-mismatched cadaveric lung transplant. The patient received three
      separate mononuclear cell infusions over a 9-month period, each containing 1 x
      10(6) CD3+ mononuclear cells per kilogram. Complete clinical, radiological, and
      pathological remission was achieved with this treatment regimen. The response
      correlated with in vivo reconstitution of normal EBV-specific cytotoxic activity
      and cytotoxic T lymphocyte precursor frequency. Use of allogeneic HLA-compatible
      mononuclear cells may thus offer an additional mode of therapy for EBV-related
      lymphoproliferative disease in selected solid organ transplant recipients
      refractory to conventional therapies.

PMID- 9197370
TI  - High prevalence of GB virus-C/hepatitis G virus infection in liver transplant
      recipients.
AB  - BACKGROUND: To determine the prevalence of GB virus-C/hepatitis G virus (GBV
      C/HGV) infection in liver transplant recipients transplanted for non-hepatitis C
      virus indications, 44 patients transplanted for cryptogenic, autoimmune,
      hepatitis B, or cholestatic liver disease and 91 non-liver transplantation (LT)
      patients with similar diagnoses seen in the same study period (control group)
      were studied. METHODS: HGV RNA was detected by reverse transcription polymerase
      chain reaction with primers from the 5'-untranslated region. RESULTS: GBV-C/HGV
      RNA was commonly detected in post-LT patients compared with the control group
      (28/44 [64%] vs. 13/91 [14%]; P<0.001). GBV-C/HGV infection was not related to
      the number of blood products transfused, a particular surgeon, or a specific
      liver disease. GBV-C/HGV infection also had no significant impact on the post-LT
      clinical profile. CONCLUSIONS: We conclude that GBV-C/HGV infection is very
      common in LT recipients, but that it has minimal clinical impact in this
      population.

PMID- 9197371
TI  - Administration of exogenous interleukin-2 abrogates spontaneous rat liver
      allograft acceptance but does not affect long-term established graft survival.
AB  - BACKGROUND: Spontaneous tolerance to the orthotopic liver allograft uniformly
      occurs in the DA (RT1a) to PVG (RT1c) rat combination despite a fully allogeneic
      barrier. METHODS: To assess whether spontaneous acceptance might be the
      consequence of a T cell help deficit at the time of the first exposure of
      alloantigens to the host, we studied the effect of exogenous interleukin (IL)-2
      injections at the time of liver transplantation and during long-term follow-up.
      RESULTS: Although spontaneous acceptance of the liver allograft constantly ensued
      in the DA to PVG combination, a daily injection of recombinant IL-2 (3 x 10(5) U)
      uniformly provoked acute cellular rejection of the liver allograft and
      consequently the death of animals by postoperative day 5-6. Simultaneous to the
      graft loss, hepatic enzymes (alanine aminotransferase) increased more than 50
      fold in IL-2-treated recipients, whereas similar IL-2 treatment did not produce
      any hepatic dysfunction in syngeneic animals. By immunohistology, the expression
      of the alpha chain of the IL-2 receptor, usually undetectable in untreated
      animals, was evident on CD4 and CD8 lymphocytes infiltrating the liver graft. In
      contrast, a similar IL-2 regimen and even higher IL-2 doses (x 10(6) U) did not
      abrogate the liver allograft survival during long-term follow-up. CONCLUSIONS:
      Our results demonstrate that spontaneous rat liver allograft acceptance may be
      abolished by exogenous IL-2 injections, which suggests that an "inherent T cell
      help deficit" might be implicated in the spontaneous acceptance mechanisms of DA
      to PVG liver allografts.

PMID- 9197372
TI  - The presence of hepatitis B core antibody does not preclude kidney donation: lack
      of viral DNA in the serum and biopsies of core antibody-positive donors and
      clinical follow-up.

PMID- 9197373
TI  - The synergistic effects of cyclosporine and sirolimus (reply)

PMID- 9197374
TI  - Acquired deficiency of functional C1-esterase inhibitor in HIV type 1-infected
      patients.

PMID- 9197375
TI  - Preliminary evidence for partial restoration of immune function in HIV type 1
      infection with potent antiretroviral therapies: clues from the Fourth Conference
      on Retroviruses and Opportunistic Diseases.
AB  - Critical advances in understanding the pathogenesis and treatment of HIV-1
      infection have been made. These include the following: delineation of the
      replication kinetics of HIV in all stages of disease, underscoring the role of
      viral replication in disease pathogenesis; development of highly sensitive
      quantitative assays to determine viral load in infected individuals; and potent
      new antiretroviral drugs, the availability of which has provided a tool for the
      investigation of viral pathogenesis and immunopathogenesis, and has permitted the
      demonstration of the clinical efficacy of combination therapies. The results of
      studies of potent antiretroviral combination therapies presented at the Fourth
      Conference on Retroviruses and Opportunistic Infections (January 22-26, 1997,
      Washington, D.C.) demonstrate that such therapies are capable of at least
      partially restoring the immune system that is damaged by infection with HIV-1.
      This includes evidence for the ability of potent therapies to begin to reverse
      the abnormalities of maturation, activation, and function that are attributable
      directly or indirectly to the CD4+ helper T lymphocyte population.

PMID- 9197376
TI  - Dendrite cell-T cell mixtures, isolated from the skin and mucosae of macaques,
      support the replication of SIV.
AB  - Previous studies have shown that HIV-1 exploits dendritic cells (DCs) to
      replicate and spread among CD4+ T cells. The DCs within mucosal surfaces may be
      especially important, but these are more difficult to access. To study more
      extensively the properties of DCs and other leukocytes from skin and different
      mucosae, DCs were isolated from uninfected macaques and their sensitivity
      assessed to infection with SIV in vitro. Dendritic cells and T cells readily
      emigrated from organ cultures of macaque skin, as described previously for
      humans. In addition, characteristic cells emigrated from explants of mucosae,
      both nasopharyngeal (adenoid and tonsil) and genital (vagina and cervix). The
      macaque DCs reacted with the monoclonals that are used to study human DCs, such
      as MAbs to CD40, CD86, CD83, and the p55 protein. When SIV was added to the DC-T
      cell mixtures from these different organs, extensive replication was observed in
      all but the cervical leukocytes. SIV replication occurred without the use
      mitogens, and with virus that had been grown in a cell line in the absence of
      mitogens and IL-2. Most of the newly synthesized viral protein is observed in
      syncytia. Therefore, mixtures of DCs and T cells isolated from mucosal surfaces
      served as a naturally permissive environment for SIV replication.

PMID- 9197377
TI  - Effects of human immunodeficiency virus and colony-stimulating factors on the
      production of interleukin 6 and tumor necrosis factor alpha by
      monocyte/macrophages.
AB  - Patients infected with human immunodeficiency virus (HIV) frequently have
      increased production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF
      alpha), and these cytokines may in turn contribute to the disease pathogenesis.
      It has been hypothesized that secretion of these cytokines by HIV-exposed
      mononuclear cells or HIV-infected monocyte/macrophages (M/Ms) is the principal
      source of their overproduction in HIV-infected patients, and the present study
      was undertaken to explore this issue. We observed that in the absence of
      endotoxin or cytokines, M/Ms productively infected by HIV do not produce
      detectable IL-6 or TNF-alpha. However, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), a cytokine that enhances HIV replication in M/Ms and is
      frequently used to propagate monocytotropic strains of HIV, can induce the
      relatively long-term production of IL-6 (up to 47 U/ml) and TNF-alpha (up to 47
      pg/ml) by M/Ms, even in the absence of HIV. Also, HIV induced production of a
      relatively small (< or = 9 U/ml) quantity of IL-6 in M/Ms stimulated with
      macrophage-colony stimulating factor (M-CSF). Finally, while highly concentrated
      HIV induced production of both cytokines by either M/Ms or peripheral blood
      mononuclear cells (PBMCs), this production was almost completely eliminated when
      care was taken to avoid contamination of HIV by endotoxin. These data suggest
      that the excess IL-6 and TNF-alpha in HIV-infected patients does not simply
      result from their production by HIV-infected M/Ms and that alternative mechanisms
      are involved in this process.

PMID- 9197378
TI  - Expression of cell adhesion molecules at the surface of in vitro human
      immunodeficiency virus type 1-infected human monocytes: relationships with tumor
      necrosis factor alpha, interleukin 1beta, and interleukin 6 syntheses.
AB  - Further evidence suggests that cell adhesion molecules (CAMs) expressed on the
      surface of human immunodeficiency virus type 1 (HIV-1)-infected cells are
      regulated during lentiviral infection. To address this hypothesis we have
      investigated the kinetic pattern of CAM expression at the surface of HIV-1Ba.L
      infected human monocytes during the first 72 hr of infection. A significantly
      lower expression of CD18 and CD54 as well as a decrease in CD44 expression level
      were observed at the surface of infected monocytes when compared with mock
      infected cultures. No modification of CD11a, CD11b, CD11c, CD58, and CD62L
      expression was detected. Except for CD18, the expression of which at the cell
      surface is decreased, no modification of CD44 and CD54 expression was observed
      after heat-inactivated HIV-1 treatment of monocytes. Investigation of soluble
      forms of CAMs (sCAMs) and cytokine production in the culture supernatants of
      infected monocytes showed a peak of sCD44, TNF-alpha, IL-1beta, and IL-6 release
      between 2 and 24 hr after infection. Treatment of monocytes with monoclonal
      antibodies (MAbs) against CAMs showed that engagement of some CAMs may trigger
      TNF-alpha and IL-1beta production. In addition, pretreatment of infected
      monocytes with a TNF-alpha synthesis inhibitor, RP 55778, or with MAbs directed
      against IL-1beta, confirmed the role of TNF-alpha and IL-1beta in the regulation
      of CD18, CD44, and CD54 expression.

PMID- 9197379
TI  - Thalidomide and thalidomide analogs reduce HIV type 1 replication in human
      macrophages in vitro.
AB  - Thalidomide is currently being evaluated for efficacy in alleviating some
      manifestations of HIV-1 infection. To determine whether thalidomide has any
      direct effects on HIV-1 infection, we investigated the effect of thalidomide and
      also of three structural analogs of thalidomide on HIV-1 replication in vitro in
      human monocyte-derived macrophages. The thalidomide analogs were previously shown
      to inhibit TNF-alpha production in vitro at much lower concentrations than
      thalidomide. In HIV-1-infected macrophages treated with thalidomide or
      thalidomide analogs, viral replication was reduced by 60 to 80% as determined by
      measuring viral RT activity in the culture supernatants. In all experiments the
      analogs inhibited HIV-1 replication more efficiently than did thalidomide. The
      drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a
      decrease in NF-kappaB-binding activity in nuclear extracts of HIV-1-infected
      macrophages. The role of NF-kappaB in the drug-induced inhibition of HIV-1
      replication was confirmed using an NF-kappaB-defective mutant virus to infect
      macrophages.

PMID- 9197380
TI  - Inhibition of HIV type 1 RNA dimerization by antisense DNA corresponding to the
      17-nucleotide sequence downstream from the splice donor site of HIV type 1 RNA.
AB  - HIV-1 RNA dimerization involves at least two key regions, one located upstream
      from the splice donor (SD) site, and the other located downstream from the SD
      site. To determine the precise location and the mechanism of action of the
      downstream region, we constructed a model system using a synthetic HIV-1 RNA
      fragment (HXB2, 455-1146), which dimerized at relatively low salt concentrations
      (100 mM KCl, 1 mM MgCl2). We tested in this system antisense DNAs that are
      complementary to both the upstream and downstream regions of HIV-1 RNA for their
      possible inhibitory effects on dimerization. Antisense DNAs complementary to
      nucleotides 773-789 located downstream from the SD site effectively inhibited
      dimerization of HIV-1 RNA. These inhibitory antisense DNAs hybridized with the
      dimer form of HIV-1 RNA, and dissociated the dimer into monomers. However,
      antisense DNAs complementary to the region upstream from the SD site did not
      hybridize with the dimer, although they inhibited RNA dimerization and also
      dissociated the preformed dimer.

PMID- 9197381
TI  - Anti-HIV type 1 activity of sulfated derivatives of dextrin against primary viral
      isolates of HIV type 1 in lymphocytes and monocyte-derived macrophages.
AB  - The anti-HIV-1 activity of sulfated derivatives of dextrin was tested in
      activated peripheral blood mononuclear cells and in monocyte-derived macrophages
      using low-passage syncytium-inducing and non-syncytium-inducing primary viral
      isolates of HIV-1. All four compounds blocked infection in a dose-dependent
      manner. Dextrin 2-sulfate blocked infection with a 90% inhibitory concentration
      (IC90) of 69 microg ml(-1). The IC90 for dextrin 3-sulfate was 50 microg ml(-1)
      and for dextrin 6-sulfate was 14 microg ml(-1). Increasing the number of sulfate
      groups to three per glucan molecule (dextrin 2-, 3-, and 6-sulfate) did not
      reduce the IC90 further (13 microg ml(-1)) compared to dextrin 6-sulfate. There
      was no significant difference in the concentration required to block infection of
      activated peripheral blood mononuclear cells when compared with monocyte-derived
      macrophages, irrespective of whether low-passage syncytium-inducing or non
      syncytium-inducing primary viral isolates of HIV-1 were used. Dextrin 2-sulfate
      and dextrin 6-sulfate also reduced the transmission of HIV-1 in experiments
      performed using peripheral blood mononuclear cells from HIV-1-positive patients
      by 6- to 251-fold in a limiting dilution tissue culture infectious dose assay.
      Sulfated dextrins were not toxic to either primary lymphocytes or macrophages at
      the concentrations tested. Having previously shown that the cell surface binding
      of sulfated dextrins is dependent on the position of the negatively charged
      sulfate groups, we now show that their anti-HIV-1 activity in primary lymphocytes
      and macrophages is also dependent on the same arrangement. A phase I/II clinical
      trial of dextrin 2-sulfate is now in progress.

PMID- 9197382
TI  - Mucosal immune response to an HIV C4/V3 peptide following nasal or intestinal
      immunization of rabbits.
AB  - The HIV env-encoded synthetic peptide T1-SP10MN(A) contains immunodominant
      epitopes of the C4/V3 regions of gp120. The mucosal immunogenicity of this
      peptide in various vaccine preparations was first tested in rabbits using
      chronically isolated Thiry-Vella (T-V) ileal loops. Intestinal and serum samples
      collected from rabbits immunized via T-V loops demonstrated secretory IgA (S-IgA)
      and IgG anti-T1-SP10MN(A), respectively, when assayed by ELISA. Intranasal
      delivery of the peptide supplemented with cholera toxin (CT) resulted in serum
      IgG and S-IgA anti-T1-SP10MN(A) in vaginal and nasal secretions. This study
      further demonstrates the utility of rabbits as a convenient animal model for HIV
      vaccine research and the relationship between nasal immunization and vaginal
      immunity.

PMID- 9197383
TI  - Quinolinic acid and lymphocyte subsets in the intrathecal compartment as
      biomarkers of SIV infection and simian AIDS.
AB  - Cerebrospinal fluid (CSF) samples were collected from monkeys infected with
      SIVmac251 (SIV) or HIV-1/SIVmac chimeric viruses (SHIV(HXBc2) and SHIV(89.6P)) to
      investigate quinolinic acid (QUIN) levels in the intrathecal compartment. CSF
      levels of QUIN were elevated in the SIV-infected monkeys, especially in animals
      with end-stage disease, and in those infected with pathogenic SHIV(89.6P), but
      not after infection with the nonpathogenic construct SHIV(HXBc2). QUIN elevations
      occurred in association with reduced CD4+ and increased CD8+ lymphocytes,
      cellular alterations that were more pronounced in CSF than in the blood. These
      findings support the view that the intrathecal compartment provides a unique
      window on viral infection, and are in keeping with the a priori prediction that
      QUIN increases primarily in response to more pathogenic viral strains.

PMID- 9197384
TI  - Genetic analysis of an HIV type 2 subtype B virus from a Spanish individual with
      AIDS.

PMID- 9197386
TI  - Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated
      antigen-1 in experimental Schistosoma mansoni infection and in synchronous
      periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser
      scanning microscopy, and immunoelectron microscopy.
AB  - Adhesion molecules play an important role in inflammatory and immunological
      responses. We assessed the expression pattern of intercellular adhesion molecule
      1 (ICAM-1) and lymphocytefunction-associated antigen-1 (LFA-1) in the livers of
      mice experimentally infected with Schistosoma mansoni and in synchronous hepatic
      granulomas induced by injection of soluble egg antigen (SEA)-coupled Sepharose
      beads in a mesenteric vein of mice. By immunohistochemistry, confocal laser
      scanning microscopy, and immunoelectron microscopy, ICAM-1 was localized on
      endothelial cells, sinusoidal-lining cells (Kupffer cells and sinusoidal
      endothelium), the hepatocyte cell membrane facing Disse's space, and inflammatory
      cells in the granuloma. LFA-1 was visualized on the inflammatory cells of the
      granuloma and on phagocytic sinusoidal-lining cells, most likely Kupffer cells.
      ICAM-1- and LFA-1-immunoreactive cells were present in the granuloma as early as
      at 3 days after injection of SEA-coupled beads and persisted with time. As
      granulomas became older, nonimmunoreactive granuloma cells appeared. We conclude
      that adhesion molecules play an important role in the genesis of the schistosomal
      granuloma.

PMID- 9197385
TI  - Sequence of gp41env immunodominant region of HIV type 1 group O from west central
      Africa.

PMID- 9197387
TI  - Altered transport properties of pentamidine-resistant Leishmania donovani and L.
      amazonensis promastigotes.
AB  - Pentamidine-resistant clones of Leishmania donovani and L. amazonensis
      promastigotes were developed by increase of the drug pressure in the culture
      medium and characterized. The resistant clones could grow in 40 and 20 microM
      pentamidine as determined for L. donovani and L. amazonensis, respectively, with
      50% inhibitory concentrations (IC50 values) being 140 and 60 microM, which were
      18 and 75 times higher than those recorded for the parental clones, respectively.
      Biochemical analysis of the clones showed that the acquired pentamidine
      resistance was specific (no cross-resistance to unrelated drugs and no
      reversibility with verapamil) and stable in vitro and in vivo. Pentamidine
      resistance is related to decreased drug uptake and highly increased efflux in
      both clones of Leishmania spp., accompanied by an alteration in polyamine
      carriers. Furthermore, a modification of the uptake of pyrimidine nucleosides and
      several amino acids by these resistant clones indicates alterations in the
      surface membrane.

PMID- 9197388
TI  - Effects of the synergistic action of febantel and pyrantel on the nematode
      Heterakis spumosa: a light and transmission electron microscopy study.
AB  - The present study proved that combined administration of pyrantel and febantel to
      Heterakis spumosa-infected mice yielded clear synergistic effects (seen in a
      quicker expulsion of the worms and a significant higher degree of worm
      degeneration), whereas the different doses of both drugs never reached the same
      efficacy, when given alone. It is concluded that the synergistic action of
      pyrantel and febantel on the functions of different organs of the parasites
      (muscle, nerve, inertine etc.) seen in the rodent model - also holds for the gut
      dwelling nematodes of the dog.

PMID- 9197390
TI  - The effect of high n-3 fatty acids diets on the ultrastructural development of
      Eimeria tenella.
AB  - A study of development of Eimeria tenella in chickens fed high n-3 fatty acids (n
      3FA) diets showed ultrastructural degeneration of both asexual and sexual
      parasite stages. Abnormal shedding of asexual and sexual parasite developmental
      stages into the cecal lumen was also observed. Ultrastructural degeneration was
      characterized by cytoplasmic vacuolization, chromatin condensation within the
      nucleus, a lack of parasitophorous vacuole delineation, and, in some cases, a
      complete loss of parasite ultrastructural organization. The results of this study
      indicate that diets high in n-3FA may be useful in the control of avian coccidia.

PMID- 9197389
TI  - Differentiation of Entamoeba histolytica from E. dispar facilitated by monoclonal
      antibodies against a 150-kDa surface antigen.
AB  - Murine monoclonal antibodies (mAbs) were produced against an n-octyl-beta-D
      glucopyranoside-extracted fraction of trophozoites of Entamoeba histolytica HM
      1:IMSS. Four of the mAbs were reactive with a 150-kDa surface antigen
      characterized by Western-immunoblot analysis under nonreducing conditions. When
      the reactivity of the four mAbs with nine reference strains of E. histolytica was
      examined by an indirect fluorescence antibody test, two of the mAbs (EH3015 and
      EH3023) were found to react with all nine strains and the other two mAbs (EH3056
      and EH3126) reacted with seven strains. The four mAbs did not react with any E.
      dispar reference strain or with other enteric protozoan parasites. The reactivity
      of EH3015 and EH3023 with numerous isolates of E. histolytica and E. dispar
      collected in our laboratories was also examined. The 2 mAbs reacted with all of
      the 37 E. histolytica isolates tested but did not react with any of the 33
      isolates of E. dispar. These results indicate that common antigenic epitopes of
      E. histolytica are on the 150-kDa surface molecule and that mAbs can distinguish
      between E. histolytica and E. dispar.

PMID- 9197391
TI  - Evaluation of a gel-immunization technique used with two different Immucox
      vaccine formulations in battery and floor-pen trials with broiler chickens.
AB  - The use of a gel-immunization technique with Immucox vaccination was compared and
      evaluated against other immunization methods in battery and floor-pen
      immunization trials. Gel immunization was found to be superior to immunization by
      gavage, by spray cabinet, or by the conventional delivery method of Immucox in a
      battery trial. Significantly enhanced protection as measured by weight gain,
      coupled with the establishment of a more uniform primary immunizing infection as
      evidenced by greater intestinal lesions and increased oocyst shedding, was seen
      in gel-immunized birds. In addition, cross-protective battery trials determined
      that the strain of Eimeria maxima found in the Immucox vaccine failed to elicit
      protection against a recent field isolate of E. maxima as measured by average
      weight gain and lesion scores. A reformulation of the Immucox vaccine that
      included the field isolate of E. maxima was required to elicit a protective
      immune response against challenge by the field strain. A floor-pen experiment
      demonstrated that gel immunization of 1-day-old roaster chickens resulted in
      performance parameters of average weight gain, average bird weight, and feed
      conversion that did not differ significantly from those recorded for medicated
      nonimmunized birds.

PMID- 9197392
TI  - Morphological differences in Blastocystis cysts-an indication of different
      species?
AB  - Cyst forms of Blastocystis that show disparate morphology in relation to the
      previously described cysts were detected in faecal material from animal hosts.
      Transmission electron microscopy was performed without attempts to isolate or
      concentrate Blastocystis from the faecal material. Large, multinucleate cyst
      forms were found in faecal material from Macaca monkeys. These cyst forms
      measured up to approximately 15 microm in diameter and were often larger than
      vacuolar forms present in the same samples. Four or more nuclei were frequently
      seen in the cysts. Multiple individual cysts enclosed by a single fibrillar layer
      were found in faecal material from domestic chickens. Each individual cyst within
      the multiple cyst form measured approximately 3-4 microm in diameter and appeared
      to be uninucleate.

PMID- 9197393
TI  - Toxoplasma gondii virulence markers identified by random amplified polymorphic
      DNA polymerase chain reaction.
AB  - Genomic DNAs from 35 Toxoplasma gondii strains were amplified by random amplified
      polymorphic DNA (RAPD) polymerase chain reaction (PCR) using 18 arbitrary 10-mer
      primers. At least four primers were found to generate DNA fragments that
      discriminate the 35 T. gondii strains into a genotype of virulent strains and a
      genotype of avirulent strains. Primer B12 was found to generate a virulence
      specific fragment and primers B5, C8, and C20 were found to generate avirulence
      specific fragments, which in all cases clearly identified either the virulence
      phenotype or the avirulence phenotype, respectively. In addition, the DNA
      polymorphic bands detected were analyzed by parsimony and distance analysis. A
      similar genetic relationship among the T. gondii strains was determined by the
      two phylogenetic methods, which use completely different assumptions. Consistent
      with the division of the 35 strains into a genotype of virulent strains and a
      genotype of avirulent strains, both analyses revealed 2 clonal lineages directly
      correlated with murine virulence. These results strongly support the hypothesis
      that the genus Toxoplasma may actually contain two clonal lineages correlated
      with virulence, which have evolved independently following their initial
      separation.

PMID- 9197394
TI  - Isoenzymes of Eimeria from the domestic fowl: electrophoretic variants among
      species, strains and clones.
AB  - Electrophoretic variation of enzymes in five Eimeria spp. of the domestic fowl,
      including nine strains, ten single-sporocyst clones and two single-sporozoite
      clones of E. acervulina, three strains each of E. maxima and E. tenella, two
      strains of E. praecox and one strain of E. necatrix, were assayed using cellulose
      acetate electrophoresis. Ten enzymes [aldehyde oxidase (AO), alkaline phosphatase
      (ALP), amylase (AMY), fumarate hydratase (FUM), glucose-6-phosphate dehydrogenase
      (G6PDH), glucose phosphate isomerase (GPI), glutamate-oxaloacetate transferase
      (GOT), isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH) and
      phosphoglucomutase (PGM)] were analyzed for their ability to distinguish between
      these species and strains. Enzymatic activity of G6PDH, GPI, IDH, MDH and PGM was
      detected in all the Eimeria spp. examined. Strains within each species were
      characterized by the same electrophoretic variant of G6PDH. Electrophoretic
      variants of GPI and PGM were the most valuable in the identification of inter-
      and intra-specific variation, particularly in the field strains of E. acervulina
      and E. tenella. These two enzymes were used to examine single-sporocyst and
      single-sporozoite clones derived from two strains of E. acervulina. The enzymes
      in E. maxima appeared to be conserved, showing no variation among strains with
      the five enzymes detected. Relative mobilities, calculated as described in this
      paper, were found to be consistent between different electrophoresis runs and may
      serve as a reference when this medium is used.

PMID- 9197395
TI  - Differential responsiveness of humans with early-stage schistosomiasis
      haematobium to Schistosoma haematobium soluble adult-worm and egg antigens.
AB  - Schoolchildren (7-8 years old) infected with Schistosoma haematobium were tested
      for lymphocyte proliferative responses, in vitro granuloma formation (IVGF), and
      cytokine release in T-cell Western assays and for serum antibody reactivity by
      enzyme-linked immunosorbent assay (ELISA) and immunoblotting against S.
      haematobium soluble adult-worm (SAWA) and egg (SEA) antigens. The
      lymphoproliferative response rate of individual subjects against 10 SAWA and 15
      SEA electroseparated bands ranged from 0 to 33% and from 11 to 66%, respectively.
      The SAWA bands essentially failed to elicit significant IVGF, in contrast to the
      SEA bands, all of which were capable of inducing IVGF from peripheral blood
      mononuclear cells (PBMC) of 30-80% of individual donors. The exclusive ability of
      SEA bands to induce IVGF could not be attributed to selective release of
      interleukin 2 (IL-2), IL-4, or interferon-gamma, as SEA and SAWA bands were
      capable of eliciting release of a similar array of cytokines in supernatants of 4
      day PBMC cultures. The antibody response to SEA was stronger than that to SAWA,
      yet the proportion of SAWA bands binding humoral antibodies of individual donors
      was significantly larger than that observed for SEA. The study thus suggests that
      humans with early-stage S. haematobium infection respond poorly to SAWA but mount
      strong cellular immune responses to SEA that result in granuloma and antibody
      formation.

PMID- 9197396
TI  - The prevalence of Cryptosporidium parvum and C. muris in Mus domesticus, Apodemus
      sylvaticus and Clethrionomys glareolus in an agricultural system.
AB  - Wild mice and voles were tested for Cryptosporidium during a 2-year survey at an
      agricultural site in Warwickshire, United Kingdom. C. parvum and C. muris, the
      two cryptosporidial species known to infect mammals, were detected. Prevalence
      figures of 22%, 21% and 13% noted for C. parvum for Mus domesticus, Apodemus
      sylvaticus and Clethrionomys glareolus, respectively, were higher than those
      recorded for C. muris at 10%, 6% and 2%. C. parvum causes the sometimes severe
      diarrhoeal disease cryptosporidiosis in many hosts, but the wild rodents were
      asymptomatic. The discovery of C. muris in A. sylvaticus and C. glareolus
      confirms a wider distribution in wild rodents than has previously been reported.
      Rodents may represent a significant reservoir of Cryptosporidium with a high
      potential for infection of man and livestock due to cohabitation.

PMID- 9197397
TI  - Kinetoplast DNA minicircles are inherited from both parents in genetic crosses of
      Trypanosoma brucei.
AB  - In the order Kinetoplastida, genetic exchange has been demonstrated only in the
      genus Trypanosoma. Analysis of kinetoplast DNA (kDNA) in genetic crosses of T.
      brucei has shown that whereas maxicircles are inherited uniparentally,
      minicircles are inherited from both parents. This result was confirmed for a new
      cross of T. b. brucei and T. b. rhodesiense by restriction enzyme digestion and
      Southern analysis of purified kDNA. By hybridisation with small minicircle
      derived probes, we could demonstrate the presence of particular parental
      minicircles in the kDNA of hybrid progeny clones. All hybrid clones had inherited
      two minicircles from one parent despite two of the four clones having maxicircles
      from the other parent. The results suggest that rather than small-scale exchange
      of minicircles between parental networks, gross breakdown and reassembly of the
      minicircle network occurs during genetic exchange.

PMID- 9197398
TI  - Potentiation of the antimalarial activity of atovaquone by doxycycline against
      Plasmodium falciparum in vitro.
AB  - The effect of doxycycline, obtained from human volunteers administered
      doxycycline, on the minimum inhibitory concentration (MIC) of atovaquone was
      determined against the K1 and FC27 isolates of Plasmodium falciparum in vitro.
      Doxycycline concentrations ranging from 0.10-1.18 microg/ml added to atovaquone
      produced MIC ratios [atovaquone + doxycycline/atovaquone alone] ranging from 0.38
      to 0.70. These results suggest that the antimalarial activity of atovaquone is
      potentiated by doxycycline. Additionally, these drugs may be rational partners
      for the treatment and prophylaxis of falciparum malaria.

PMID- 9197400
TI  - Electron microscopy studies on the a-bacteroids in the fat bodies of the lantern
      bug Pyrops candelaria Linn. (Homoptera: Fulgoridae).
AB  - The ultrastructure of alpha-bacteroids in relation to the fat-body cells of the
      lantern bug Pyrops candelaria was described. The fat-body-cell cytoplasm
      contained numerous mitochondria, rough endoplasmic reticula, vacuoles, and
      storage granules. Its nucleus had scattered chromatin materials. The alpha
      bacteroid was enveloped by three membrane layers, namely, the plasma membrane,
      the cell wall, and the membrane envelope. Its cytoplasm contained amorphous dense
      bodies. The bacteroid reproduced by binary fission. Tracheoles were also found
      among fat-body cells.

PMID- 9197399
TI  - In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an
      indigenous plant in Shillong, India.
AB  - The in vitro activity of root-tuber-peel extract of Flemingia vestita, an
      indigenous plant consumed by the natives in Northeast India, was tested against
      helminth parasites. Live parasites (nematode: Ascaris suum from pigs, A.
      lumbricoides from humans, Ascaridia galli and Heterakis gallinarum from domestic
      fowl; cestode: Raillietina echinobothrida from domestic fowl; trematode:
      Paramphistomum sp. from cattle) were collected in 0.9 % physiological buffered
      saline (PBS) and maintained at 37 +/- 1 degrees C. In vitro treatment of the
      parasites with the crude extract (50 mg/ml) in PBS revealed complete
      immobilization of the trematode and cestode in about 43 and 20 min, respectively.
      However, the cuticle-covered nematodes did not show any change in physical
      activity and remained viable even after a long period of exposure to the extract.
      Exposure of R. echinobothrida to genistein (0.5 mg/ml), an active principle
      isolated from the root-tuber peel, caused spontaneous loss of movement
      (paralysis) in 4.5 h, which was slower than the time required for praziquantel,
      the reference flukicide and cestodicide. The treated parasites showed structural
      alteration in their tegumental architecture. This study suggests the vermifugal
      activity of this plant extract against trematodes and cestodes.

PMID- 9197401
TI  - Modifications in the rhythm of schizogony in Plasmodium chabaudi chabaudi
      associated with the selection of chloroquine resistance.
AB  - A high level of drug resistance was obtained with a line of Plasmodium chabaudi
      maintained under intense chloroquine selection pressure according to the
      protocols established for P. berghei. The main objective of this work was to
      verify if the characteristic asynchronous schizogonic rhythm of naturally
      resistant rodent malaria parasites was also found when the drug resistance was
      induced experimentally. The degree of resistance was evaluated through the use of
      the "2% delay test" (DT) and the schizogonic rhythm, by reference to the
      synchronicity index (SI). The strain had originally a DT of 4.26 and an SI of
      0.52. Following the application of 80 mg/kg chloroquine at each passage, as early
      as at the 8th passage the parasites rapidly became resistant and asynchronous. At
      the 17th passage the DT was 3.32 and the SI, 0.20. In the drug-resistant line the
      original indices, both the DT and the SI, were restored after deep-freezing,
      sporogony, or passage through a Percoll gradient, or simply by repeated
      intravenous subinoculations of blood. The clear correlation between
      asynchronicity and drug resistance is easily explained by the action of
      chloroquine, which favours the schizogonic cycles initiated by latent merozoites.

PMID- 9197402
TI  - Human amebic liver abscess: expression of intercellular adhesion molecules 1 and
      2 and of von Willebrand factor in endothelial cells.
AB  - Liver invasion by amebas with production of amebic liver abscess (ALA) is the
      most common extraintestinal lesion produced by the protozoan parasite Entamoeba
      histolytica. This hepatic damage is characterized by the presence of extensive
      tissue necrosis. However, little is known about the parasite and host factors
      involved in the process of tissue damage. During the early establishment of
      amebas in the liver parenchyma as well as during the extension of the tissue
      necrosis, parasites interact with sinusoidal endothelial cells. As a consequence
      of ameba-endothelial cell interactions, the latter can be activated and express
      proinflammatory factors that could be related to tissue destruction. We studied
      by immunohistochemistry the localization of antigenic molecules of E. histolytica
      trophozoites and of molecules such as intercellular adhesion molecule 1 (ICAM-1),
      ICAM-2, and von willebrand factor in activated endothelial cells of human ALA,
      which could be related to the pathophysiological mechanisms of tissue destruction
      in amebiasis.

PMID- 9197403
TI  - In vitro sensitivity of Leishmania donovani to organometallic derivatives of
      pentamidine.

PMID- 9197405
TI  - An isoamylase with neutral pH optimum from a Flavobacterium species: cloning,
      characterization and expression of the iam gene.
AB  - The gene encoding an isoamylase with neutral pH optimum (iam) from a
      Flavobacterium species was cloned using a PCR probe generated from highly
      conserved regions of amylolytic enzymes. Active isoamylase was expressed from a
      4.9-kb Pst I fragment in Escherichia coli, and was detected in the extracellular
      medium by a plate assay. The iam nucleotide sequence has an open reading frame of
      2334 nucleotides (778 amino acids) with a GC content of 69%. Sequence analysis
      suggests that transcriptional control of the Flavobacterium sp. iam gene is
      mediated through the product of a malT regulatory gene. The deduced amino acid
      sequence of iam contained an N-terminal signal peptide of 32 amino acids, and was
      61% homologous with Pseudomonas amyloderamosa isoamylase. The mature enzyme,
      which was engineered for overexpression in E. coli and purified to homogeneity,
      has a relative molecular mass of 83 kDa, a pH optimum of 6-7, and a highest rate
      of hydrolysis for glycogen (but did not cleave pullulan). Polyclonal antiserum
      generated from purified donor isoamylase cross-reacted with crude and purified
      recombinant isoamylase from E. coli. This is the first report of the cloning,
      characterization, and sequence of an novel isoamylase that has a neutral pH
      optimum. A comparison of the sequence of Flavobacterium sp. iam with acidic
      isoamylase from Pseudomonas sp. identified putative residues which may be
      associated with the pH for optimal activity of isoamylases.

PMID- 9197404
TI  - Isolation and partial characterization of a fatty-acid-binding protein from
      Ascaris suum reproductive tissue.
AB  - A 12-kDa fatty-acid-binding protein was purified to homogeneity from Ascaris suum
      reproductive tissue as confirmed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. N-terminal amino-acid-sequence analysis of the protein revealed
      its identity with the ABA-1 allergen protein isolated from A. suum pseudocoelomic
      fluid. Fatty-acid binding by the protein from A. suum reproductive tissue was
      investigated using the Lipidex 1000 assay, which revealed the presence of a
      single class of fatty-acid-binding sites with an apparent dissociation constant
      for palmitate of about 0.8 microM.

PMID- 9197406
TI  - Cloning, nucleotide sequence and transcriptional analysis of the uvrA gene from
      Neisseria gonorrhoeae.
AB  - A recombinant plasmid capable of restoring UV resistance to an Escherichia coli
      uvrA mutant was isolated from a genomic library of Neisseria gonorrhoeae.
      Sequence analysis revealed an open reading frame whose deduced amino acid
      sequence displayed significant similarity to those of the UvrA proteins of other
      bacterial species. A second open reading frame (ORF259) was identified upstream
      from, and in the opposite orientation to the gonococcal uvrA gene.
      Transcriptional fusions between portions of the gonococcal uvrA upstream region
      and a reporter gene were used to localise promoter activity in both E. coli and
      N. gonorrhoeae. The transcriptional starting points of uvrA and ORF259 were
      mapped in E. coli by primer extension analysis, and corresponding sigma70
      promoters were identified. The arrangement of the uvrA-ORF259 intergenic region
      is similar to that of the gonococcal recA-aroD intergenic region. Both contain
      inverted copies of the 10 bp neisserial DNA uptake sequence situated between
      divergently transcribed genes. However, there is no evidence that either the
      uptake sequence or the proximity of the promoters influences expression of these
      genes.

PMID- 9197407
TI  - Molecular cloning and characterization of Drosophila genes encoding small GTPases
      of the rab and rho families.
AB  - We have isolated eight genes from Drosophila, small GTPases. They can be
      classified into three rab family genes (Drab2, Drab5, Drab11) and five rho family
      genes (Drac1a, Drac1b, Drac3, Dcdc42, DrhoA). While Drac3 is a novel type of rac
      gene, others are homologues of known mammalian genes for small GTPases. Northern
      blot analyses showed that all the genes are expressed throughout all
      developmental stages from embryo to adult. In situ hybridization to embryos
      revealed that Drab2, Drac1b, and Drac3 are highly expressed in the nervous
      system, in the trunk mesoderm, and in the cephalic mesoderm, respectively. Since
      hemocytes are derived from the cephalic mesoderm, we carried out double stainings
      using a hemocyte marker anti-peroxidasin antibody and Drac3 in situ
      hybridization. We found that Drac3 is expressed in hemocyte precursor cells. In
      the Drac3 deficiency embryos, the hemocyte precursor cells start to differentiate
      normally, but never develop into mature hemocytes, indicating that Drac3 is
      essential for their maturation. The DrhoA and Dcdc42 genes complemented S.
      cerevisiae rho1 and cdc42 mutations in the same manner as human rhoA and CDC42,
      respectively. These results suggest functional similarity between Drosophila and
      mammalian small GTPase genes.

PMID- 9197408
TI  - The acetate regulatory gene facB of Aspergillus nidulans encodes a Zn(II)2Cys6
      transcriptional activator.
AB  - Genetic studies have indicated that the facB gene of Aspergillus nidulans is a
      major regulatory gene involved in acetamide and acetate utilisation. Sequencing
      of the facB gene revealed that it encodes a protein that contains an N-terminal
      GAL4-like Zn(II)2Cys6 (or C6 zinc) binuclear cluster for DNA binding, leucine
      zipper-like heptad repeat motifs and central and C-terminal acidic alpha-helical
      regions, consistent with a function as a DNA-binding transcriptional activator.
      The Zn(II)2Cys6 cluster shows strong similarity with those of the Saccharomyces
      cerevisiae carbon metabolism regulatory proteins CAT8 and SIP4. A significant
      level of similarity with CAT8 is found throughout the length of the protein,
      suggesting at least partial functional homology. The facB genes of Aspergillus
      oryzae and Aspergillus niger were also sequenced and found to be highly
      conserved. Deletion of the facB gene confirmed that it is required for growth on
      acetate as a sole carbon source. Functional dissection using deletion and fusion
      constructs and in vitro mutagenesis indicated that the Zn(II)2Cys6 cluster and
      the C-terminal end of the protein are required for function.

PMID- 9197409
TI  - Zebedee: a novel copia-Ty1 family of transposable elements in the genome of the
      medically important mosquito Aedes aegypti.
AB  - We have utilised PCR to directly identify a novel family of copia-Ty1
      retrotransposable elements (RTPs) in the genome of the mosquito Aedes aegypti.
      Two members of the family have been sequenced in their entirety and their
      structural characteristics determined. ZebedeeI is 3505 bp long and appears to be
      flanked by 21bp direct repeat sequences. A single open reading frame (ORF) of 972
      amino acids has the coding potential for a polyprotein with homology
      corresponding to the conserved amino acid motifs of Long Terminal Repeat (LTR)
      retrotransposon protease, integrase and reverse transcriptase. ZebedeeII likewise
      shares significant homology with these regions and also appears to be flanked by
      short direct terminal repeat sequences of 22 bp. Fifty copies of the 22 bp repeat
      sequence are present abutting the 5' end of ZebedeeII, with two (partial)
      representatives of this repeat sequence being present at the 3' end. The Zebedee
      family appears to have a low middle repetitive copy number in different strains
      of Ae. aegypti; and transcripts of the elements have been detected in cultured
      mosquito cells by RT-PCR. Despite the lack of a gag homologue or the LTR
      hallmarks of previously characterised copia-Ty1 RTPs, phylogenetic analyses place
      Zebedee within this group, showing considerable homology to copia from Drosophila
      melanogaster.

PMID- 9197410
TI  - The homeodomains of the heterodimeric bE and bW proteins of Ustilago maydis are
      both critical for function.
AB  - In Ustilago maydis, pathogenic development is controlled by the multiallelic b
      mating type locus. b encodes two different homeodomain proteins, bE and bW, that
      dimerize only when they originate from different alleles. The heterodimer is
      thought to act as a transcriptional regulator of pathogenicity genes. To address
      the contribution of individual homeodomains to the function of the hetereodimer,
      amino acids presumed to be critical for the function of homeodomains were altered
      by introducing deletions and single amino acid substitutions. This analysis
      demonstrated that both homeodomains are essential for function of the bE/bW
      complex. All point mutations affecting conserved amino acids in bW resulted in
      non-functional proteins. For bE the mutational analysis revealed that certain
      features of the homeodomain, like base-specific contacts and contacts to the
      sugar phosphate backbone, contribute to function. However, the structural
      requirements for function of the bE homeodomain appear to be more flexible than
      those of the bW homeodomain. We compare our data with the related systems in
      Schizophyllum commune, Coprinus cinereus and Saccharomyces cerevisiae.

PMID- 9197411
TI  - Tolerance of low pH in Schizosaccharomyces pombe requires a functioning pub1
      ubiquitin ligase.
AB  - A strain of Schizosaccharomyces pombe carrying a disrupted Na+/H+ antiporter gene
      (sod2::sup3-5), in addition to the common auxotrophic mutations, ade6-216, ura4
      D18 and leu1-32, is highly sensitive to media adjusted to pH 6.9. Reversion
      analysis of this strain yielded a group of revertants capable of growth at pH
      6.9. Two of the revertants elongated and failed to form colonies at pH 3.5.
      Genetic characterization of one of the pH-sensitive elongated strains, J227,
      showed the presence of two independently segregating mutations. One, pub1
      (protein ubiquitin ligase 1), has recently been reported as an E3 protein
      ubiquitin ligase involved in cdc25 turnover. The second has been named elp3-1
      (elongated at low pH). Genetic dissection of the original strain revealed that
      poor growth at high pH was due to the presence of the auxotrophic markers,
      suggesting a possible inhibitory effect of high pH on the function of permeases
      responsible for uptake of the necessary nutrients. Suppression of the high pH
      sensitivity required the presence of both the pub1-1 and elp3-1 mutations. While
      the pub1-1 mutation reduced the capacity of cells to tolerate relatively moderate
      concentrations of LiCl (3 mM) in liquid culture, it was capable of partially
      suppressing the extreme Li+ sensitivity caused by the sod2 disruption. Under
      these conditions, the growth of pub1-1 sod2::ura4 double mutant cells was
      improved over that of either pub1-1 or sod2::ura4 cells. The elp3-1 mutation had
      no effect on the Li+ tolerance in either wild-type or sod2::ura4 backgrounds.
      pub1-1 cells are elongated and incapable of colony formation at pH 3.5. In
      contrast, elp3-1 cells are elongated at pH 3.5 and pH 5.5 (the normal pH of
      minimal medium) but can form colonies under both conditions. J227 cells are
      significantly longer than either single mutant at pH 3.5 and do not form colonies
      but are visually similar to elp3-1 cells at pH 5.5. Complementation cloning in
      the J227 background yielded a genomic clone of pub1, allowing us to define the
      intron-exon structure of the gene. Sequences with high homology to the predicted
      amino acid sequence of pub1 have been identified in Saccharomyces cerevisiae
      (RSP5/NPI1), human (hRPF1), mouse (mNedd4), and rat (rNedd4). Based on the nature
      of our mutant selection, the pH-sensitive phenotype of the strains selected, and
      the known involvement of RSP5/ NPI1 in membrane permease turnover in S.
      cerevisiae, we hypothesize a role for pub1, either directly or indirectly, in
      regulating membrane transport processes. This is further supported by the broad
      range of effects that the pub1-1 mutation exerts on overall performance of cells
      at high and low external pH, and in the presence of toxic levels of Li+.

PMID- 9197412
TI  - The regulatory protein MucR binds to a short DNA region located upstream of the
      mucR coding region in Rhizobium meliloti.
AB  - The Rhizobium meliloti MucR protein is known to regulate the biosynthesis of the
      two exopolysaccharides, succinoglycan and galactoglucan. The mucR gene was
      successfully overexpressed in Escherichia coli BL21 cells by heat shock induction
      using a two-plasmid system. Cell extracts of the production strain contained
      about 20% of a polypeptide of 17 kDa apparent molecular mass, corresponding to
      the size expected for MucR. As shown by an electrophoretic mobility shift assay,
      these extracts were active in the specific retardation of a 219-bp DNA fragment
      including 134-bp of the non-coding region upstream of the mucR gene. Primer
      extension analysis showed that this DNA fragment was located within the
      transcribed region upstream of the mucR gene. Competition experiments revealed
      that a 44-bp sequence present within the 134-bp upstream of the mucR gene
      contained the MucR binding site. Although binding of MucR to this site exhibited
      a moderate dissociation constant of Kd approximately 1.4 x 10(-7) M, the reaction
      was highly specific since fragments containing binding sites for the homologous
      Ros protein from Agrobacterium tumefaciens were not able to compete for MucR
      binding.

PMID- 9197413
TI  - Studies on spontaneous promoter-up mutations in the transcriptional activator
      encoding gene phIR and their effects on the degradation of phenol in Escherichia
      coli and Pseudomonas putida.
AB  - The activator-encoding gene phlR was identified upstream of the plasmid-encoded
      operon for phenol degradation in Pseudomonas putida strain H by cassette
      mutagenesis and DNA sequence analysis. The deduced amino acid sequence of PHLR
      shows high homology to DmpR of P. putida sp. CF600 and to the chromosomally
      encoded PhhR of P. putida P35X reported previously. Trans-activation of phenol
      degradation was observed when phlR was overexpressed in a phlR insertion mutant.
      Transconjugants of Escherichia coli carrying pPGH11, which contains the complete
      set of phl genes, are unable to grow on phenol as carbon source. However, two
      types of mutants were selected for further characterization that were able to
      metabolize phenol as sole source of carbon and energy. In both types of mutants
      enhanced expression of phlR is responsible for the Phl+ phenotype. In type I
      (pPGH13) a deletion of 1 bp made the -35 region and the spacing between the -35
      and -10 regions of the phlR promoter more similar to the consensus structure. In
      type II (pPGH14) a duplication of the phlR 5' region was identified that includes
      part of the -35 motif and reduces the spacing between the -35 and -10 regions. In
      addition, due to the duplication of part of phlR, the distance from the phlR
      promoter to the catabolic phl operon is increased. Different transcriptional
      start sites have been identified by primer extension analysis in clones harboring
      pPGH14 or the wild type phlR. Quantitative primer extension analysis revealed
      that the greatest amount of phlR transcript is expressed from the partial, phlR
      duplication. Growth on phenol and phenol hydroxylase activity reflect the high
      level of phlR transcript in E. coli transconjugants. Overexpression of PhlR was
      also observed when pPGH14 was transferred into P. putida, and results in earlier
      induction of the phenol degradation operon relative to the wild-type strain.

PMID- 9197414
TI  - HU protein binding to the replication origin of the rolling-circle plasmid pKYM
      enhances DNA replication.
AB  - The RepK protein, which is encoded by the rolling-circle plasmid pKYM, binds to
      the PR I site in the pKYM DNA replication origin. We have identified HU as a
      protein that binds to the PR II and PR III sites in the replication-enhancing
      region which is downstream of PR I. DNA footprinting assays show that HU binds to
      these two sites only when RepK is bound to PR I, and that HU also enhances the
      binding of RepK to PR I. In vivo, pKYM was unable to transform an HU null strain.
      Two mutant RepK proteins, RepKW179Y, which contains a Trp-to-Tyr exchange at
      position 179, and RepKD277L, which contains an Asp-to-Leu mutation at residue
      277, initiate DNA replication in vivo in the absence of HU. In vitro, these
      mutant RepK proteins form more stable complexes with the pKYM origin region than
      does the wild-type RepK protein. These results indicate that HU plays a role in
      the formation of a stable RepK-origin complex, which is required for the
      initiation of pKYM DNA replication.

PMID- 9197415
TI  - Enhancement of Ty transposition at the ADH4 and ADH2 loci in meiotic yeast cells.
AB  - Genome polymorphism in the yeast Saccharomyces cerevisiae is frequently the
      result of transposition and recombination events involving Ty elements. The
      activity of these retrotransposons is closely integrated with the life cycle of
      the host. Ty transcription is repressed in diploid, but not haploid, cells and is
      induced by certain stress conditions. We have found that Ty transposition at the
      ADH4 and ADH2 loci is not only active, but 50-fold more frequent in meiotic yeast
      than in mitotic cells. These data provide a further example of the success of Ty
      elements in maximising their own chances of spread and survival while minimising
      the risks to the host yeast population.

PMID- 9197416
TI  - Analyses of Saccharomyces cerevisiae Cdc7 kinase point mutants: dominant-negative
      inhibition of DNA replication on overexpression of kinase-negative Cdc7 proteins.
AB  - Saccharomyces cerevisiae Cdc7 kinase is required for initiation of S phase, and
      its kinase activity, which is positively regulated by Dbf4 protein, reaches
      maximum at the G1/S boundary. In this study, we constructed Cdc7 point mutants
      (T281E, T281A, D182N, D163N, and T167E) and examined the effect of each mutant on
      growth. All the mutants lost the ability to complement temperature-sensitive
      growth of cdc7(ts) mutants at a low protein level, whereas T281A (putative target
      of phosphorylation) and T167E (residue involved in substrate recognition)
      restored the growth of cdc7(ts) when overproduced to a high level. Three putative
      kinase-negative mutants (T281E, D182N, and D163N) inhibited growth when
      overexpressed in a wild-type strain. Analyses of DNA content and morphology
      revealed that most cells were arrested as dumbbells with 1C DNA, indicative of a
      block in the G1 to S transition. This growth inhibition was suppressed by co
      overexpression of the wild-type Cdc7 or Dbf4 protein. Furthermore, deletion of
      the Dbf4 protein-binding region in each Cdc7 mutant resulted in loss of growth
      inhibitory effect. Thus, dominant-negative effects of T281E, D182N, and D163N on
      growth can be best explained by inactivation of the wild-type Cdc7 function
      through titration of Dbf4 by these inactive kinases. Our results are consistent
      with the notion that association of Dbf4 with Cdc7 is essential for the G1 to S
      transition in S. cerevisiae.

PMID- 9197418
TI  - A silent mutation in the ftsH gene of Escherichia coli that affects FtsH protein
      production and colicin tolerance.
AB  - Among Escherichia coli tolZ mutants tolerant to colicins E2, E3, and D, one,
      KHI10, had a high frequency of lambda lysogenization, like the tolZ21 mutant, but
      unlike tolZ21 KHI10 grew on nonfermentable carbon sources. The tolZ10 gene of
      KHI10 was cloned and sequenced, and found to have a silent mutation in the ftsH
      gene, causing an alteration of a minor codon, CUA, for Leu-5 to a suboptimal
      codon, CUC. In spite of the change in a minor codon, the amount of the FtsH
      protein present in mutant cells was much less than that in the parental strain.
      In vivo transcription of the tolZ10 gene was not decreased relative to the wild
      type ftsH gene. Analysis of other silent mutations altering the Leu-5 codon (CUA)
      to CUG or CUU (optimal and suboptimal codons, respectively) revealed that the
      decrease in concentration of FtsH was seen only with the CUC (tolZ10) codon.
      Prediction of the mRNA secondary structure suggested that the change from A to C
      extends the base pairing region longer by one base pair at the root of the stem
      structure, thus sequestering the Shine-Dalgarno sequence and decreasing the rate
      of the translational initiation of FtsH.

PMID- 9197417
TI  - The Cdk-like protein PCTAIRE-1 from mouse brain associates with p11 and 14-3-3
      proteins.
AB  - PCTAIRE-1 is a member of the cyclin-dependent kinase (cdk)-like class of
      proteins, and is localized mainly in the mammalian brain. Using the yeast two
      hybrid system we screened a mouse brain cDNA library with PCTAIRE-1 as bait, and
      isolated several clones coding for the mouse homologs of the following proteins:
      p11 (also known as calpactin I light chain) and the eta, theta (also known as
      tau) and zeta isoforms of 14-3-3 proteins. We confirmed that these four proteins
      interact with PCTAIRE-1 by demonstrating the biochemical interactions using the
      pure recombinant proteins. The fact that 14-3-3 proteins are known to interact
      with many other intracellular proteins (such as C-kinase, Raf, Bcr, P13-kinase)
      and p11 with annexin II (a major pp60(v-src) and C-kinase substrate) suggests
      that PCTAIRE-1 might be part of multiple signal transduction cascades and
      cellular protein networks.

PMID- 9197419
TI  - Cloning and genetic mapping of wheat telomere-associated sequences.
AB  - Wheat telomere-associated sequences (TASs) were cloned using a Vectorette
      approach and sequenced. Reverse primers specific to the TASs were combined with
      labelled degenerate telomere primers in PCR reactions containing total genomic
      DNA as template. Amplification products were separated on sequencing gels. In
      total, seventeen primer combinations provided 47 polymorphic fragments. Nine of
      these mapped beyond the most distal RFLP markers and defined the ends of seven
      chromosome arms. Seven of the nine terminal fragments were derived from a 118-bp
      tandem repeat, indicating that subtelomeric tandem repeat sequences provide an
      efficient means to target chromosome ends. A telomere cloning strategy and the
      terminal and interstitial location of TASs are discussed.

PMID- 9197420
TI  - Sequential functioning of Sym-13 and Sym-31, two genes affecting symbiosome
      development in root nodules of pea (Pisum sativum L.).
AB  - Two Fix- mutants of pea (Pisum sativum L.) which are unable to fix molecular
      nitrogen, E135f (sym-13) and Sprint-2Fix- (sym-31), were crossed to create the
      doubly homozygous recessive line, named RBT (sym-13, sym-31). The ultrastructural
      organization of nodules of the RBT line was compared with that of each of the two
      parental mutant lines and with the original wild-type genotypes of the cultivars
      Sparkle and Sprint-2. It was shown that the RBT line is similar to the mutant
      line Sprint-2Fix- in having abnormal symbiosome composition and bacteroids with
      relatively undifferentiated morphology. Because the phenotypic manifestation of
      the sym-31 mutant allele suppresses the phenotypic manifestation of the sym-13
      mutant allele, it is concluded that the function of the gene Sym-31 (which is
      mutated in the Sprint-2Fix- line) is necessary at an earlier stage of symbiosome
      development than the gene Sym-13 (which is mutant in the E135f line).

PMID- 9197421
TI  - Roles of RpoS (sigmaS), IHF and ppGpp in the expression of the hmp gene encoding
      the flavohemoglobin (Hmp) of Escherichia coli K-12.
AB  - The Escherichia coli K-12 gene hmp encodes the flavohemoglobin Hmp. A hmp
      promoter phi(hmp-lacZ)-operon fusion was constructed in the chromosome and its
      activity measured during the growth cycle. Logarithmically growing cultures had
      low levels of phi(hmp-lacZ) expression, which increased two-fold at the onset of
      stationary phase in rich medium. The effect was abolished in a strain carrying a
      null allele of the gene rpoS encoding the stationary phase-specific sigma subunit
      of RNA polymerase sigmaS. A himA mutation resulted in a 1.5-fold increase in
      expression of phi(hmp-lacZ) but did not affect growth phase-dependent regulation.
      A single transcriptionial start site was found for hmp, located 38 bp upstream of
      the initiation codon. Putative Fnr boxes at positions -2 to +11 occur in the hmp
      promoter region.

PMID- 9197422
TI  - The malEFG gene cluster of Streptomyces coelicolor A3(2): characterization,
      disruption and transcriptional analysis.
AB  - The malEFG gene cluster of the Gram-positive mycelial actinomycete Streptomyces
      coelicolor A3(2) was cloned and sequenced. MalEFG show only limited similarity to
      homologues involved in maltose and maltodextrin transport in other bacteria.
      Disruption of malE prevented the utilization of maltose as carbon source.
      Transcription of malE was induced by maltose and repressed by glucose.

PMID- 9197423
TI  - Association of a deletion polymorphism of the angiotensin-converting enzyme gene
      with left-ventricular hypertrophy in Japanese women with essential hypertension;
      multicenter study of 1,919 subjects.
AB  - The relationship of an insertion/deletion (I/D) polymorphism of the angiotensin
      converting enzyme (ACE) gene to left-ventricular hypertrophy in individuals with
      essential hypertension (EH) was investigated in a large population of Japanese
      men and women. The ACE genotype of 762 subjects with EH (425 men and 337 women)
      and 1,157 healthy controls (604 men and 553 women) was determined by polymerase
      chain reaction analysis. The distribution of ACE genotypes did not differ
      significantly between patients with EH and control in both men and women. For
      women with EH, the DD genotype was positively associated with the thickness of
      the interventricular septum and inversely associated with the left ventricular
      end-diastolic dimension, both determined by echocardiography. In contrast, the DD
      genotype was not associated with any echocardiographic parameter in men with EH.
      These results indicate that the DD genotype is a risk factor for left-ventricular
      hypertrophy in Japanese women with EH, but not for Japanese men.

PMID- 9197424
TI  - Long-term changes in left ventricular mass, chamber size and function after valve
      replacement in patients with severe aortic stenosis and depressed ejection
      fraction.
AB  - We studied 21 patients undergoing valve replacement for severe aortic stenosis
      and marked left ventricular dysfunction (mean ejection fraction 27 +/- 7.9%)
      without significant coronary disease or other valve diseases. At 5-60 months
      (average 26 +/- 18) after surgery, the patients underwent a clinical history,
      physical examination and a complete M-mode, two-dimensional and Doppler
      transthoracic echocardiographic study. Thirteen patients were examined with
      cardiopulmonary exercise testing. Two patients with a low preoperative
      transvalvular pressure gradient (<50 mm Hg) died postoperatively. Nineteen
      patients were tested at follow-up. All patients showed an improvement in
      functional class, an increase in ejection fraction (EF), a normalization in left
      ventricular diameters, volumes and stress indices and a reduction in left
      ventricular mass which correlated with EF increase. Cardiopulmonary exercise
      testing showed a good exercise capacity. In conclusion, in patients affected by
      severe aortic stenosis and marked preoperative left ventricular dysfunction valve
      replacement induces a favorable remodeling of the left ventricle, as shown by a
      late postoperative examination. The regression of hypertrophy is a positive event
      which correlates with the improvement in EF.

PMID- 9197425
TI  - DDD(R) pacing with automatic mode switch in patients with paroxysmal atrial
      fibrillation following AV nodal ablation.
AB  - Optimal pacing in patients with paroxysmal atrial fibrillation/flutter following
      AV node ablation remains to be determined because VVIR pacing cannot restore AV
      synchronization and conventional DDD(R) pacing cannot properly cope with atrial
      tachyarrhythmias. The objective of the present investigation was to study the
      clinical outcome of 16 of these patients who received a new DDDR pacemaker with
      an automatic mode switch (Thera DR; Medtronic) immediately after AV node
      ablation. Arrhythmia-related symptoms before ablation were palpitations in 12,
      dizziness in 10, exercise intolerance in 8, and syncope in 6 patients. Pacing
      modes at hospital discharge were DDDR (n = 14) and DDD (n = 2) with an activated
      mode switch in all patients. After 1 month 12 patients were symptom free.
      Clinical events occurred in 4 patients (palpitations in 2, dizziness in 1, chest
      pain in 1, and fatigue in 1), which could be relieved in 3 patients. At discharge
      as well as at the 1-month follow-up, Holter ECG recorded a total of 12 episodes
      of atrial fibrillation in 5 patients, which were correctly detected by the
      pacemaker and followed by mode switching. At the 3-month follow-up (n = 14), 12
      patients were symptom free and 2 continued to report symptoms which could not be
      resolved. All patients remained on an automatic mode switch in either the DDDR (n
      = 12) or DDD (n = 2) mode. There were no hints of inappropriate mode switching or
      reports of pacemaker syndrome, and there were no new symptoms related to
      automatic mode switching. The patients studied were highly symptomatic before
      implantation due to paroxysmal atrial fibrillation/flutter. After the first
      follow-up, 81% of the patients reported no symptoms. Paroxysmal atrial
      fibrillation/flutter combined with a high-degree AV-block seems no longer to be a
      contraindication for AV-synchronous pacing.

PMID- 9197426
TI  - QRS polarity on 12-lead surface ECG. A criterion for the differentiation of right
      and left posteroseptal accessory atrioventricular pathways.
AB  - In this study, we tried to disclose certain electrocardiogram (ECG) criteria that
      might be useful in the classification of posteroseptal accessory atrioventricular
      pathways as right and left in patients with pre-excitation in whom the accessory
      pathway localization was verified by subsequent successful ablation. Twenty such
      patients with posteroseptal accessory pathways (mean age 34.9 +/- 9.8; 11 male, 9
      female) were included in the study. Localization of the accessory pathway was
      right posteroseptal in 13 (65%) and left posteroseptal in 7 (35%). Common to all
      these 20 patients with posteroseptal accessory pathways was a QRS polarity
      positive in lead L1 and negative in leads D3, aVL. In patients with right
      posteroseptal accessory pathways, QRS polarity was negative in lead V1 in all and
      positive in lead V2 in 90%. On the other hand, none of the patients with left
      posteroseptal accessory pathways showed negative QRS polarity in lead V1. In
      conclusion, these findings strongly suggest that in patients with pre-excitation,
      a QRS polarity negative in lead V1 and positive in lead V2 is an important
      surface ECG finding that signifies right-sided localization of a posteroseptal
      accessory pathway. In cases with left posteroseptal accessory pathways, QRS
      polarity in leads V1 and V2 has been found to be either biphasic or positive.

PMID- 9197427
TI  - Serial prognostic capabilities of electrocardiographic indices of infarcted and
      hibernating myocardium in predicting short- and long-term outcome following
      coronary artery bypass surgery.
AB  - The present study was performed to test the hypothesis that patients with a large
      amount of ischemic (hibernating) myocardium are most likely to develop a
      perioperative myocardial infarction undergoing coronary artery bypass grafting
      (CABG). Furthermore, we evaluated the Selvester QRS scoring system as a
      postoperative prognostic tool. A relationship between a high amount of
      hibernating myocardium determined by ventriculographic and electrocardiographic
      investigations and an increased risk of perioperative myocardial infarction was
      found. The Selvester QRS scoring system used in diagnosing and prognosing after
      acute myocardial infarction was proven valid in predicting prognosis after CABG
      as well.

PMID- 9197428
TI  - Left ventricular endoaneurysmorrhaphy: effect on left ventricular size, shape and
      function.
AB  - Left ventricular (LV) endoaneurysmorrhaphy is a relatively new surgical procedure
      with excellent results. Forty-five patients underwent surgical repair of LV
      aneurysm with LV endoaneurysmorrhaphy from 1991 to 1995. The main indication for
      operation was angina pectoris (71%). Concomitant myocardial revascularization was
      performed in 97% of the patients. The operative mortality rate was 2.2%.
      Pharmacologic inotropic support was required in 31% and mechanical support in
      15%. Mean echocardiographic ejection fraction improved from 29.6% preoperatively
      to 48.3% postoperatively (p <0.001). LV end-diastolic volumes were 195 +/- 63 and
      118 +/- 44 ml before and after surgery (p <0.01). Intraoperative transesophageal
      echocardiography revealed normal or near-normal LV shape in all cases. The mean
      follow-up was 34.0 +/- 9.2 months (16-50 months) and 1 patient died 9 months
      postoperatively. We conclude that endoaneurysmorrhaphy improves LV geometry and
      function in patients with LV aneurysms and can be performed with low surgical
      risk even in patients with large aneurysms and severely depressed LV function.
      ........

PMID- 9197429
TI  - Laser versus radiofrequency catheter ablation of ventricular myocardium in dogs:
      a comparative test.
AB  - To compare the effects of laser light with those of radiofrequency (RF) current
      on ventricular myocardium, a total of 36 lesions (endocardial approach n = 10
      each and epicardial approach n = 8 each) were produced by either transcatheter
      laser (Nd:YAG, 1,064 nm, 30 W, 30 s) or RF (70 degrees C, 30 s) catheter
      applications in the beating hearts of 4 dogs. Volumes of coagulated myocardium in
      endo-/epicardial approaches were 996 +/- 73/1,075 +/- 82 (laser) and 111 +/-
      38/44 +/- 5 mm3 (RF). RF lesions showed intramural bleeding, rupture and
      dissociation of myocardial fibers, tissue vaporization with crater and thrombus
      formation. Transcatheter application of laser light produced significantly larger
      and better reproducible lesions than RF current, without undesirable effects on
      the ventricular walls.

PMID- 9197431
TI  - Pathophysiology of precordial ST-segment depression in inferior wall acute
      myocardial infarction: an echocardiographic appraisal.
AB  - Precordial ST-segment depression (PSD) in inferior wall acute myocardial
      infarction (IAMI), especially when maximal in leads V4-V6, has been shown to
      portend a higher rate of heart failure and mortality. To better understand the
      pathophysiology behind this phenomenon, we evaluated patients with a first IAMI
      by echocardiography 48-72 h after the acute event, using segmental scoring (0 =
      normal to 3 = dyskinesia) of left ventricle wall motion, and a dichotomous
      assessment of right ventricle involvement. Patients were categorized into 3
      groups: I = no PSD (n = 14); II = maximal PSD in leads V1-V3 (n = 28); III =
      maximal PSD in leads V4-V6 (n = 8). As compared with group I, patients in groups
      II-III had more severe wall motion abnormalities in inferior segments (1.36 +/-
      0.97 vs. 2.19 +/- 1.74, p = 0.04), and a similar trend for posterior and lateral
      segments (1 +/- 1.75 vs. 2 +/- 2.41, p = 0.11), translating into a worse total
      left ventricle score (2.36 +/- 2.34 vs. 4.25 +/- 4.05, p < 0.05). Frequency of
      right ventricle involvement was similar in patients with and without PSD (6 (43%)
      vs. 9 (25%), p = 0.37). Segmental scores for groups I, II, and III, respectively,
      were not different for inferior (1.36 +/- 1, 2.25 +/- 1.82 and 2 +/- 1.51, p =
      0.24), posterior and lateral (1 +/- 1.75, 1.96 +/- 2.32 and 2.13 +/- 2.9, p =
      0.38), and septal, anteroseptal and anterior segments (0 +/- 0, 0.04 +/- 0.19 and
      0.13 +/- 0.35, p = 0.28). Right ventricle abnormalities occurred in 43, 21 and
      38% of patients in groups I, II and III, respectively, p = 0.3. Thus, IAMI with
      PSD is associated with worse left ventricle wall motion. However, since patients
      with maximal PSD in leads V4-V6 do not have greater wall motion abnormalities or
      higher rate of right ventricle involvement, their poorer prognosis cannot be
      explained by worse systolic dysfunction. We propose that maximal PSD in leads V4
      V6 reflects transient diffuse ischemia and altered diastolic distensibility due
      to extensive coronary artery disease, causing increased left ventricle end
      diastolic pressure.

PMID- 9197432
TI  - Causal attribution by patients, their spouses and the physicians in relation to
      patient outcome after a first myocardial infarction: subjective and objective
      outcome.
AB  - Ninety-eight men <60 years of age with a first myocardial infarction (MI), their
      spouses and treating physicians were interviewed at the patients'
      hospitalization. The aim was to determine the three groups' perception of the
      causes of the patients' MI, and the importance of those for patient outcome 6
      months after the MI. Patients and spouses agreed in general and attributed the MI
      to similar causes, while the patients and physicians had a lower level of
      agreement. The patients tended towards the more 'social' and 'psychological'
      items, while the physicians relied on medical information. The causal
      attributions of each of the groups were more important than background variables
      when subjective and objective outcome measures were estimated.

PMID- 9197430
TI  - Effect of gallopamil on myocardial microperfusion in patients with stable effort
      angina: a randomized, cross-over, double-blind, placebo-controlled trial.
AB  - We evaluated the efficacy and safety of daily administration of gallopamil 150
      mg/day and its effects on myocardial perfusion in a medium-term, randomized,
      double-blind, cross-over, placebo-controlled trial. We studied 19 patients (17
      males and 2 females; mean age 57 +/- 6.8 years) with stable effort angina,
      angiographically documented coronary artery disease and reversible perfusion
      defects during exercise thallium-201 myocardial scintigraphy of at least one
      segment of the left ventricle. After 2 weeks of a single-blind placebo run-in
      period, during which each patient underwent at least 2 exercise tests and a 48
      hour Holter ECG recording, all patients were treated with either placebo or
      gallopamil 50 mg t.i.d. for 28 days. At the end of this period, patients crossed
      over to the alternate regimen. This phase was double blind. After treatment with
      placebo or gallopamil, patients underwent exercise tests, 24-hour Holter ECG
      recording and thallium-201 myocardial scintigraphy. Weekly angina frequency and
      trinitroglycerin (TNT) consumption and safety were also evaluated. No patients
      dropped out of the study because of major side effects. The number of total
      ischemic and symptomatic events recorded at 24-hour ECG monitoring, weekly angina
      frequency and TNT consumption were significantly reduced during gallopamil
      treatment. After gallopamil administration, exercise duration significantly
      increased (run-in: 419 +/- 116 s, placebo: 420 +/- 118 s, gallopamil: 511 +/- 144
      s; p < 0.05), and ST segment depression was significantly reduced (run-in: -1.3
      +/- 0.3 mm, placebo: -1.3 +/- 0.3 mm, gallopamil: -0.94 +/- 0.68 mm; p < 0.01),
      while heart rate, systolic blood pressure and rate-pressure product were
      unchanged at rest, at submaximal and at peak exercise. Qualitative and
      quantitative evaluation of myocardial perfusion and the myocardial uptake
      percentage of thallium-201 in ischemic zones were significantly improved by
      gallopamil treatment. These findings demonstrate that gallopamil can improve
      myocardial perfusion and reduce myocardial oxygen consumption.

PMID- 9197433
TI  - Estimation of pulmonary capillary wedge pressure from M-mode mitral echograms.
AB  - We investigated whether the isovolumic relaxation time (IRT) and an interval from
      the start of opening to the maximal amplitude of the anterior mitral leaflet in
      early diastole (D-E interval) would be useful predictors of the pulmonary
      capillary wedge pressure (PCWP). We recorded M-mode mitral echograms and
      phonocardiograms in 33 patients (aged 38-70 years) with acute myocardial
      infarction (AMI) in the coronary care unit and in 34 patients (aged 40-75 years)
      with prior myocardial infarction (OMI) during cardiac catheterization. All
      patients underwent the insertion of a flow-directed pulmonary artery catheter to
      obtain the PCWP. We measured the IRT and the D-E interval from the
      phonocardiograms and the M-mode echograms. There was no significant correlation
      between the IRT and the mean PCWP (mPCWP) in patients with AMI and in patients
      with OMI. The D-E interval was significantly and inversely correlated with the
      mPCWP (r = -0.91, p <0.0001) in all patients. The regression equation was mPCWP =
      -0.42 x (D-E) +47.9. The D-E interval of < or = 75 ms indicated a high mPCWP
      (mPCWP > or = 18 mm Hg) with high sensitivity (96%) and specificity (88%). The
      derived equation was tested in a prospective group of 32 additional patients
      (aged 43-75 years). A significant correlation was observed between the predicted
      and measured mPCWP (r = 0.91, p <0.0001). Thus, the PCWP can be estimated by
      using the D-E interval derived from M-mode mitral echograms in patients in the
      coronary care unit and in patients with chronic heart disease.

PMID- 9197434
TI  - Dobutamine stress echocardiography compared with exercise thallium-201 single
      photon emission computed tomography in detecting coronary artery disease-effect
      of exercise level on accuracy.
AB  - Dobutamine stress echocardiography (DSE) and exercise thallium-201 single-photon
      emission computed tomography (SPECT) were compared for the accuracy in detecting
      coronary artery disease (CAD) in 51 consecutive patients. Twenty-six (group 1) of
      the 51 patients achieved adequate exercise end points, and 25 (group 2) did not.
      There were 38 patients with angiographically documented CAD. The overall
      sensitivity of DSE and thallium-201 SPECT in detecting CAD was 92 and 76% (p =
      NS), and the specificity was 77 and 77% (p = NS), respectively. The sensitivity
      of DSE is the same as that of SPECT in group 1 (90 vs. 90%; p = NS) and higher
      than that of SPECT in group 2 (94 vs. 61%; p < 0.05). In patients with CAD
      without a history of acute myocardial infarction or pathological Q wave on
      resting electrocardiogram, the sensitivity of DSE is the same as that of SPECT in
      group 1 (82 vs. 82%; p = NS) and also higher than that of SPECT in group 2 (90
      vs. 40%; p = 0.03). The sensitivity in detecting individual coronary artery
      lesions with DSE and thallium-201 SPECT was not affected by the exercise level.
      The agreement between DSE and thallium SPECT in detecting patients with CAD was
      88% in group 1 (kappa = 0.69; p < 0.001) and 76% in group 2 (kappa = 0.45; p =
      0.01). The agreement in detecting vascular territories with ischemia was 68% in
      group 1 (kappa = 0.30; p < 0.01) and 75% in group 2 (kappa = 0.33; p < 0.001).
      The agreement in detecting vascular territories with a scar was 87% in group 1
      (kappa = 0.55; p < 0.001) and 85% in group 2 (kappa = 0.44; p < 0.001). In
      conclusion, the sensitivity and specificity of DSE in detecting CAD are similar
      to that of thallium-201 SPECT with an exercise level > or =85% of the maximal
      predicted heart rate. However, in patients who cannot exercise adequately, DSE is
      more accurate than thallium SPECT. The agreement between DSE and thallium SPECT
      in detecting patients with CAD and identifying ischemia of individual vascular
      territories is also affected by the exercise level.

PMID- 9197436
TI  - Clinical feasibility of echocardiographic automated border detection in
      monitoring left ventricular response to acute changes of preload in normal
      subjects.
AB  - Echocardiographic automated border detection (ABD) provides an instantaneous
      measurement of left ventricular (LV) volume and its rate of change. We tested the
      clinical feasibility of ABD in monitoring on-line LV response to acute changes in
      preload. We examined 20 healthy males in the supine position, with legs elevated,
      back in the supine position, 5 min after the inflation of blood pressure cuffs at
      the root of the four limbs, 5 min after the deflation of cuffs. End-diastolic and
      end-systolic LV volumes significantly increased with elevated legs and decreased
      during cuff inflation; ejection fraction remained unchanged. Peak filling and
      peak emptying rates did not change with elevated legs and increased significantly
      during cuff inflation. The values of LV parameters were stable in the three
      resting conditions, demonstrating a good reproducibility of the ABD technique.
      Our results demonstrate that ABD may be useful in clinical practice for
      monitoring on-line small acute changes in LV volume and function.

PMID- 9197435
TI  - Assessment of the functional significance of coronary artery stenosis by
      dobutamine-atropine stress echocardiography.
AB  - This study was performed to evaluate whether dobutamine stress echocardiography
      (DSE) can provide any additional information regarding the location and severity
      of coronary artery disease (CAD) in an individual patient. DSE was performed in
      233 patients with clinical manifestations of angina pectoris. There were 162
      patients with angiographically documented CAD defined as > or = 50% diameter
      stenosis. The severity of coronary lesions was divided into three groups: 50-75,
      76-90 and >90%. The diagnostic sensitivity in detecting left anterior descending
      artery (LAD) and right coronary artery (RCA) lesions was higher for lesion
      severity of>90% than of 50-75% (p = 0.01 for LAD and p < 0.05 for RCA). The
      diagnostic sensitivity in detecting CAD was highest among patients with proximal
      coronary lesions (89% for LAD, 64% for the left circumflex artery, and 81 % for
      the RCA). When lesion severity increased from 50-75 to >90%, wall motion scores
      at peak dose during dobutamine infusion increased from 12.3 +/- 4.3 to 18.4 +/-
      5.4 (p = 0.003) in the proximal LAD lesion group and from 10.6 +/- 2.0 to 20.4 +/
      5.9 (p < 0.0001) in the mid-distal LAD lesion group. When lesion severity
      increased from 50-75 to >90%, wall motion scores at peak dose increased from 5.9
      +/- 2.0 to 8.0 +/- 2.5 (p < 0.05) in the proximal RCA lesion group and from 5.2
      +/- 2.1 to 8.1 +/- 1.9 (p < 0.05) in the mid RCA lesion group. However, the
      change in wall motion scores did not reach statistical significance in proximal
      and distal lesions of the left circumflex artery when lesion severity increased
      from 50-75 to >90%. The correlation coefficient between quantitative wall motion
      score and Gensini's score was 0.54 (p = 0.0001) in all patients and 0.6 (p =
      0.0001) in patients without myocardial infarction. In conlcusion, the functional
      significance of lesion severity and distribution can be evaluated by DSE.
      Regional dyssynergy of LAD and RCA territories during peak-dose dobutamine
      infusion was most apparent at the stenotic level >90%.

PMID- 9197437
TI  - Hernias in trocar ports following abdominal laparoscopy. A review.
AB  - BACKGROUND: With increasing numbers of laparoscopies in gynecologic surgery as
      well as the use of larger trocars more post-operative hernias can be expected.
      Most hernias occur as Richter's hernias without peritoneal lining and contain
      small or large intestines or omentum. The incidence is around 1%, but rising with
      increasing size of trocars. About one fourth of hernias are umbilical, the rest
      located extraumbilical. RESULTS: The diagnosis is typically based on the presence
      of vomiting or nausea with an extended and painful abdomen within two weeks of
      surgery and can be established by a small bowel series. However, the course can
      be prolonged and ileus can occur up to one year following laparoscopy. In the
      majority of cases the hernial content was small intestines or omentum.
      CONCLUSIONS: In order to reduce the frequency of trocar hernias it is recommended
      to apply small trocars. Fascial closure must be done when trocars of 10 mm or
      larger have been employed and the surgeon must ensure that peritoneal tissue is
      not drawn into the trocar canals when removing the probes. Also, umbilical
      hernias must be ruled out and, if found, closure must include the complete
      fascial defect. There are several techniques available for fascial closure. It is
      concluded that all precautions including fascial suturing must be taken to reduce
      the 1% incidence of post-laparoscopy hernias.

PMID- 9197438
TI  - Short stature: an obstetric risk factor? A comparison of two villages in
      Tanzania.
AB  - BACKGROUND: A short maternal stature is associated with an increased risk of
      obstructed labor due to cephalopelvic disproportion and most antenatal programs,
      including that of Tanzania, designate short women as 'at risk'. OBJECTIVE: To
      determine mean maternal height in two obstetric populations and the effect, if
      any, of maternity care practices pertaining to maternal height, on interventions
      and outcome of pregnancy and delivery. METHODS: A community based study of
      pregnancy outcome for women in two villages in rural Tanzania of different
      profiles and ethnicity. RESULTS: In Ilula 54% of cesarean sections were in the 4%
      of women under 150 cm and 39% of short women delivered in hospital. In Ikwiriri
      23% of parturients were under 150 cm and height did not correlate to the duration
      of labor, referral patterns or Cesarean section rates. There are indications that
      fertility rate is reduced in short women in Ilula but not in Ikwiriri, a result
      of the problems and risks of Cesarean section for women living in rural areas.
      CONCLUSIONS: The distribution of maternal height in the population should be
      considered when the cut-off height for the 'at risk' designation is chosen. The
      implications of attaching an 'at risk' label is discussed and a call is made for
      regional specific and agreed risk criteria.

PMID- 9197439
TI  - The clinical significance of an absent end-diastolic velocity in the umbilical
      artery detected before the 34th week of pregnancy.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical significance of
      absent or reversed (ARED) flow detected in the late second or early third
      trimester in the umbilical artery in high-risk pregnancies. METHODS: Eighty-three
      women with hypertensive disorders of pregnancy, gestational diabetes or a
      suspected disorder of the fetus (e.g. small-for-gestational age) were included in
      this retrospective study. A constant finding of ARED flow in the umbilical artery
      was registered with the pulsed Doppler method between the 23+/-0 and 33+/-6
      gestational weeks. Perinatal mortality (PNM) rates, Apgar scores and arterial
      umbilical pH values, birth weights, the frequency of SGA, gestational ages at
      birth, NICU (=neonatal intensive care unit) days, anomalic fetuses and the mode
      of delivery were registered. Mann-Whitney U-test and chi-squared test were used
      for statistical analysis. RESULTS: The PNM in the entire group under study was
      19.3% (16 infants/fetuses). The rate of structurally or chromosomally abnormal
      fetuses was 15.7% (13 infants/fetuses). When anomalic fetuses were excluded the
      PNM was 18.6%. No non-anomalic fetuses/newborns were lost in cases in which ARED
      was detected after the 30th week. No statistically significant difference was
      observed in PNM and SGA frequencies when comparing AEDV (absent end-diastolic
      velocity) fetuses with those who had REDV (reversed end-diastolic velocity). When
      anomalic fetuses were excluded the PNM rate in the AEDV group was 8.9% compared
      with the PNM rate of 35.7% in the REDV group; (p=0.03). CONCLUSIONS: An early
      ARED finding (before the 34th week) in the umbilical artery signifies a marked
      warning signal of fetal distress. In these cases the rates of perinatal morbidity
      and mortality are very high, which is a reflection of the severity of the
      condition. The majority of fetuses can, however, be saved.

PMID- 9197440
TI  - The behavior of amidolytic factor VII in smoking and non-smoking pregnant women
      in relation to their gestational age.
AB  - OBJECTIVE: Aim of the study was to assess the behavior of factor VII by
      commercial amidolytic assay in smoking and non-smoking pregnant women, and to
      compare this with the earlier reported factor VII:C levels during pregnancy and
      to discuss the role of F VII:Am with regard to thromboembolic complication in
      smoking pregnant women. METHODS: Blood samples were obtained for 75 non-smoking
      pregnant women and 109 smoking pregnant women. For the chromogenic determination
      of F VII:Am a COA-Set F VII test kit from Kabi Vitrum was used. Correlations were
      calculated by the Spearman rank method. The Mann-Whitney-U test was used for the
      statistical comparison of the median values of the smoking and non-smoking
      groups. RESULTS: Both the smoking and non-smoking group displayed a significant
      increase of F VII:Am with gestational age (r=0.53; p<0.0001 for smokers and
      r=0.55; p=0.005 for non-smokers). The median concentration of F VII:Am was
      significantly higher in stage 3 (226%-211%) and stage 4 (262%-230%) in the
      smoking group. CONCLUSION: As elevated F VII:C levels have been described to be a
      risk factor for thrombotic events, the even higher than normally already enhanced
      plasma levels of FVII:Am in smoking pregnant women may indicate an additional
      risk for both thrombosis in the pregnant and for an increased fetal morbidity and
      even mortality caused by thrombotic processes in the uteroplacental vasculature.
      The results from the present study might be an extra argument to advise pregnant
      women not to smoke or to quit smoking during pregnancy.

PMID- 9197441
TI  - Prenatal diagnosis of urinary tract abnormalities.
AB  - BACKGROUND: To compare magnetic resonance imaging with ultrasonography for the
      diagnosis of urinary tract abnormalities. METHODS: Two cases of multicystic
      dysplastic kidney, six cases of ureteropelvic junction obstruction, and one case
      of autosomal recessive polycystic kidney disease were diagnosed on antenatal
      ultrasonography and/or magnetic resonance imaging. RESULTS: In case of
      multicystic dysplastic kidney and ureteropelvic junction obstruction,
      ultrasonography showed characteristic features of their diseases. Magnetic
      resonance imaging was insufficient to diagnose these diseases. In a case of
      autosomal recessive polycystic kidney disease, ultrasonography and magnetic
      resonance imaging were both useful to show characteristic features of this
      disease, and thus made it possible to make a correct diagnosis of the disease.
      CONCLUSIONS: For a prenatal fetal diagnosis, it is necessary to observe both
      fetal anatomy and an evolution of the fetal abnormality. The above mentioned
      three types of urinary tract abnormalities changed their anatomic configurations
      and/or texture of urinary tracts as the pregnancies progressed. To observe these
      changes, the usefulness of ultrasonography is superior to that of magnetic
      resonance imaging for the present. Although ultrasonography and magnetic
      resonance imaging show fetal urinary tract abnormalities, these instruments
      should be used properly during the period of the pregnancy on case-by-case bases.

PMID- 9197442
TI  - Risk of retained placenta: multivariate approach.
AB  - BACKGROUND: To identify important covariates related to retained placenta using
      logistic regression analysis. METHODS: The study was carried out in the King
      Khalid University Hospital, Saudi Arabia, and involved 114 women who had retained
      placenta, and 116 women with normal deliveries. Chi-square test and logistic
      regression analysis were used for analysis of data. Adequacy of predictor
      variables was examined using indices of sensitivity and specificity and plots of
      probability histograms for prediction of retained placenta among patients and
      controls. RESULTS: Logistic regression analysis highlighted multiparity, induced
      labor, small placenta, and large amount of blood loss to be significantly
      associated with retained placenta. In addition, high pregnancy number, previous
      injury to uterus, and pre-term labor related significantly to retained placenta.
      Predictor variables had sensitivity of 65.5% and 87.9% specificity and achieved
      77% overall correct classification. CONCLUSIONS: These findings could be used to
      develop a predictive procedure for identifying high-risk cases of retained
      placenta.

PMID- 9197443
TI  - Umbilical cord blood sampling--a tool for delivery quality control?
AB  - BACKGROUND: Regular cord blood analysis post partum is regarded by many as one of
      the most accurate and objective methods of auditing intrapartum care. Emergency
      cesarean sections and ventouse deliveries, due to the threat of asphyxia, are
      examples where post partum acid base data from the umbilical artery ought to be a
      must. The possibility of having cord blood analyses as a routine at all
      deliveries was investigated in this study. METHODS: During a two month period
      blood samples were drawn from both the umbilical artery and vein at all vaginal
      deliveries and cesarean sections between 8 am and 4 pm. Samples were analysed for
      a complete acid base status and lactate concentration. RESULTS: True paired
      artery-venous samples for acid base data and lactate concentrations were obtained
      from 48% of the women. Sampling was especially difficult after emergency cesarean
      section and vaginal twin deliveries. Lactate analyses gave the same information
      about the metabolic state of the newborn as did BEecf. CONCLUSIONS: Cord blood
      acid base data are a superior method of retrospective analyses of CTG-tracings
      and partographs within a quality control program relating to intra partum care.
      However, routines for cord blood sampling must be well established in both the
      delivery room and in the operating theater to obtain samples from the umbilical
      artery in cases of threatening intrapartum asphyxia. A graph for easy post partum
      documentation and interpretation of acid base data is introduced.

PMID- 9197444
TI  - High progesterone is related to effective human labor. Study of serum
      progesterone and 5alpha-pregnane-3,20-dione in normal and abnormal deliveries.
AB  - BACKGROUND: The role of progesterone levels during human labor is unclear.
      OBJECTIVE: To investigate serum concentrations of progesterone and 5alpha
      pregnane-3,20-dione in normal and abnormal deliveries. METHODS: Venous and
      umbilical cord serum samples were collected from 108 parturient women. In a
      further 49 deliveries, arterial and venous umbilical cord sera were collected
      separately. The concentrations of progesterone and 5alpha-pregnane-3,20-dione
      were determined by radioimmunoassay. The delivery modes studied were: elective
      cesarean section; oxytocin-resistant dystocia; normal but induced delivery, and
      normal spontaneous delivery. RESULTS: Progesterone concentrations in maternal and
      umbilical serum were higher following normal labor than after dystocia (p<0.005)
      and elective cesarean section (p<0.005). The maternal and umbilical progesterone
      concentrations in dystocia and elective cesarean section were between 77-43% of
      those in normal labor. The concentrations did not vary between gestational weeks
      37 and 42, within the different modes of delivery. The 5alpha-pregnane-3,20-dione
      serum concentration in the fetal compartment was twice that in the maternal
      compartment (p<0.001); its concentration in venous umbilical serum was higher
      than in corresponding arterial samples (p<0.001). No distinct differences in the
      5alpha-pregnane-3,20-dione serum concentration were found with regard to parity
      or mode of delivery. CONCLUSION: High progesterone concentrations during
      parturition appear to be related to effective labor. The findings support results
      from in vitro experiments on human term myometrium.

PMID- 9197445
TI  - Psychological adjustment of infertile women entering IVF treatment:
      differentiating aspects and influencing factors.
AB  - OBJECTIVE: To evaluate the psychological adjustment of infertile women compared
      with a control group of mothers and to determine which personal or marital
      factors influence the amount of emotional disorders in the infertile group.
      DESIGN: Cross-sectional questionnaire study with a group of infertile women and a
      group of mothers attending a routine gynecological examination. SETTING:
      Infertile women and mothers received the questionnaires after a psychological or
      medical examination respectively, at a Sterility Center in a Department of
      Obstetrics and Gynaecology. PARTICIPANTS: One hundred and twenty-two infertile
      women, entering an IVF program, and 57 mothers attending a routine care visit.
      MAIN OUTCOME MEASURES: Stressful events, self-esteem, job and marital
      satisfaction, care and control measures of intimate bond, state-trait anxiety,
      depression, psychophysiological symptoms and global emotional factor scores.
      RESULTS: The organic infertile group was higher than mothers on satisfaction with
      their relationship with their husbands, perception of care and state-anxiety. The
      emotional factor scores of infertile women, controlled for stressful events, were
      influenced by a) number of IVF-cycles and availability for adoption, b) job
      position, job satisfaction and self-esteem, c) personality dimensions. State and
      trait anxiety scores were influenced by the level of global marital satisfaction.
      CONCLUSIONS: Infertile women, entering an IVF treatment program, do not
      necessarily show signs of psychological maladjustment. Their level of state
      anxiety can be considered a situational response to the treatment stress. The
      infertility condition and its treatment can be effectively dealt with by women
      having a good personality disposition, a high level of self-esteem, who are
      satisfied with their job and relationship with their husband, and who are willing
      to adopt a child as a last solution for their maternal need.

PMID- 9197446
TI  - Reduced prevalence of cervical Chlamydia infection among women requesting
      termination.
AB  - BACKGROUND: The prevalence and pattern of Chlamydia trachomatis infection among
      women requesting induced abortion in the three year period 1992-95 was evaluated
      and compared to the results of a previous study in 1982-84, where the prevalence
      of chlamydial infection had been 13.5%. METHODS: A total of 1995 women requested
      termination, 1855 (93%) of whom were tested for Chlamydia and were included in
      the study. Two types of tests for chlamydial infection, ELISA and PCR, were used
      in two consecutive periods. In addition cultures for gonorrhea were done in each
      case. Information on age, marital status, parity, gestational age and the results
      of chlamydia and gonorrhea tests of the women and sexual partners were recorded.
      RESULTS: Chlamydia trachomatis positive women were 149 (8.0%), a significant
      reduction from the previous 1982-84 study (p<0.001). Women with positive tests
      were significantly younger (80% < or = 25 years of age; p<0.001) and more
      frequently single (86.6%; p<0.001), than those with negative tests, as in the
      previous period. Of the partners, 80.4% were contacted, and 52.1% presented for
      investigation. Of those tested 42.1% were Chlamydia positive. Four women (0.2%)
      had Neisseria gonorrhea but none of the partners. CONCLUSIONS: The prevalence of
      Chlamydia trachomatis is receding among women coming for termination of
      pregnancy. As treatment before or at operation has repeatedly been shown to be of
      benefit and since the prevalence is still considerable, continued screening of
      these women is justified.

PMID- 9197447
TI  - The prevalence and severity of climacteric symptoms and the use of different
      treatment regimens in a Swedish population.
AB  - OBJECTIVES: To determine (i) the prevalence and severity of climacteric symptoms,
      and (ii) the prevalence of treatment for climacteric complaints, in a population
      based, random sample of Swedish women aged 46-62 years. MATERIAL AND METHODS: A
      random sample of 5990 women from the birth cohorts 1946, 1942, 1938, 1934 and
      1930, resident in the city of Goteborg, was obtained from the population
      register. The women were invited by letter to complete a questionnaire concerning
      general health, reproductive history, climacteric symptoms (severity graded on a
      scale 0,1,2,3) and the treatment of climacteric complaints. The overall response
      rate was 76%. RESULTS: The prevalence of climacteric symptoms was as follows:
      vasomotor symptoms 53%, depression/irritability 57%, sleeping disturbance 52%,
      muscle/joint pain 57%, loss of libido 37% and vaginal dryness 21%. Hormone
      replacement therapy (HRT) with medium potency estrogens was currently being used
      by 13.4% and 7.7% were using low potency estrogens. Medium potency estrogens had
      previously been used by 14% and 6% had used low potency estrogens. HRT was
      reported to be effective against the most common climacteric complaints in 70%
      90%. Non-hormonal treatment regimens had been used by 45% of the women and 31-63%
      reported a positive effect on climacteric symptoms. CONCLUSIONS: Although the
      majority of peri- and postmenopausal women reported suffering from climacteric
      complaints only 21% were current users of estrogens. Non-hormonal treatment
      modalities had been used by 45% of the women and were reported to have a good
      effect on climacteric symptoms in 45% compared to up to 90% of the HRT users.

PMID- 9197448
TI  - Intrauterine administration of levonorgestrel 5 and 10 microg/24 hours in
      perimenopausal hormone replacement therapy. A randomized clinical study during
      one year.
AB  - OBJECTIVE: To investigate the clinical effects especially with regard to
      histopathology and bleeding patterns by levonorgestrel (5- or 10 microg/24 h)
      released from an intrauterine system (IUS) in combination with estradiol valerate
      (2 mg) given daily or transdermal estradiol (50 microg/24 h) in perimenopausal
      women. DESIGN: A prospective randomized single blind comparison during twelve
      months. SUBJECTS: One hundred and twelve perimenopausal women with vaso-motor
      symptoms. OUTCOME MEASURES: Histopathological assessment of the endometrium,
      ultrasonographic measurement of endometrial thickness, bleeding patterns, and
      acceptability. RESULTS: A total of 108 women started the study and 12
      discontinued. The most common reason for discontinuation was frequent bleeding
      (six women). Thus, 96 (89%) women were followed for twelve months. In both the 5-
      and 10 microg levonorgestrel IUS groups the endometrium in all women but one was
      non-proliferative after twelve months and no case of hyperplasia was found.
      Irregular bleeding was reported during the first months of treatment but
      decreased after six months. At the end of the study 62% in the 5 microg- and 61%
      in the 10 microg group were amenorrhoic. The effects on bleeding patterns did not
      differ between the two levonorgestrel dosages. CONCLUSION: Continuous combined
      HRT was well accepted in perimenopausal women when the progestogen was given in
      an IUS. IUS's releasing 5- or 10 microg/24 h levonorgestrel seemed to minimize
      the progestogenic side effects and proved to be sufficient for effective
      prevention of endometrial stimulation by estrogen treatment in HRT in
      perimenopausal women.

PMID- 9197449
TI  - Pelvic floor findings in urinary incontinence--results of conditioning using
      vaginal cones.
AB  - BACKGROUND: Conservative treatment of urinary incontinence (UI) may be more
      reliable if it is associated with improved testing of pelvic floor function. The
      results of cone training in patients and healthy controls are compared. METHODS:
      Voluntary contractions of pelvic floor muscles in 16 women with genuine stress
      incontinence, 14 with mixed stress/urge incontinence, and eight healthy controls
      were assessed by digital transvaginal palpation, manometry, and inspection using
      the so-called speculum-lift test. In addition, the capability to hold vaginal
      cones was investigated. All examinations were done before and after four-week
      cone training (Femcon 20-70 g). RESULTS: Prior to cone training, no pelvic floor
      response was recordable from eight women (27%) by palpation and from seven women
      (23%) by inspection. After training, contractions were restored in all women. The
      best post-training results were obtained by palpation (27 positive responses),
      followed by manometry (25 women, 83%), and speculum-lift test (13 women, 43%).
      The capability to hold vaginal cones was also improved. Initial weights in 15 UI
      patients (50%) were lower (cone No. 1-2) than in eight healthy women (cone No.
      5). Average contractility increased from 5 to 9.7 mmHg in patients and from 17.5
      to 23.1 mmHg in healthy women. Twenty-four patients (80%) were cured (57%) or
      improved (23%). Twenty-six asked for continuation of cone training. CONCLUSIONS:
      Pelvic floor conditioning with vaginal cones is a good alternative to poor
      acceptance or insufficient availability of conventional exercises.

PMID- 9197450
TI  - Clinical and urodynamic characteristics of women with recurrent urinary
      incontinence after Burch colposuspension.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical and urodynamic
      characteristics of women with recurrent urinary incontinence after Burch
      colposuspension. MATERIAL: Fifty women subjectively complaining of recurrent
      urinary incontinence (RUI) median 6 years after Burch colposuspension and 52
      women with primary stress urinary incontinence were examined during 1991-93.
      METHODS: The participants were assessed with medical history, uro-gynecological
      examination and urodynamic investigation consisting of pad-test,
      urethrocystoscopy, cough provocation test, cystometry, urethra profilometry and
      flowmetry. RESULTS: Women with RUI demonstrated significantly increased
      incidences of recurrent lower urinary tract infection (24% vs. 8%), lumbago and
      sciatica (66% vs. 38%), rectocele (80% vs. 21%), and enterocele (24% vs. 0%)
      compared to women with primary stress urinary incontinence. Hypermobility of the
      bladder neck and urethra and palpable contraction of the levator ani muscles was
      observed significantly more often among the women with primary stress
      incontinence (90% vs. 42% and 83% vs. 56%, respectively). The leakage in women
      with RUI was significantly less pronounced than among women with primary stress
      incontinence. Detrusor instability was found significantly more often in women
      with RUI (47.51% vs. 23%). Low urethra pressure was found in five women with RUI.
      CONCLUSION: Women with RUI after Burch colposuspension seem to have a more
      pronounced pelvic floor weakness than women with primary stress urinary
      incontinence, whereas the urinary leakage is less pronounced. Recurrent lower
      urinary tract infection, lumbago and sciatica as well as detrusor instability are
      commonly observed whereas low urethral closure pressure is rare in women with RUI
      after Burch colposuspension.

PMID- 9197451
TI  - An analysis of the factors involved in the diagnostic accuracy of colposcopically
      directed biopsy.
AB  - OBJECTIVE: To compare the results of colposcopically directed biopsy with the
      final diagnosis established by the analysis of the surgical specimen, and to
      determine the clinical and colposcopic factors on which the reliability of biopsy
      is based. MATERIAL AND METHODS: Five hundred and sixty-seven women were seen by
      the same colposcopist who also performed the directed biopsies and/or the
      endocervical curettage. The final histological diagnosis identified 29 normal
      aspects (5.2%), 58 low-grade cervical intraepithelial neoplasias (CIN) (10.2%),
      448 high-grade CINs (79.0%), 16 microinvasive cancers (2.8%) and 16 occult
      invasive cancers (2.8%). The influence of several factors--such as age, parity,
      menopause, pregnancy, history of cervical treatment, site of the squamocolumnar
      junction, localization, size and severity of the lesions--on the pertinence of
      the biopsy was studied in a uni- and multifactorial analysis. RESULTS: Colposcopy
      was satisfactory in 399 patients (70.4%) in whom the colposcopic aspect was
      consistent with the final histological diagnosis in 81.2% of cases. The global
      agreement between biopsy diagnosis and final diagnosis was observed in 89.6% of
      cases. It was 84.2% for low-grade CINs, 95.8% for high-grade CINs, 31.2% for
      microinvasive cancers and 81.2% for invasive cancers. No clinical or colposcopic
      factor could be identified as independent factor associated with the diagnostic
      agreement with the directed biopsy. Conversely, concordance of biopsy was related
      to the final diagnosis since the only independent risk factors were a high-grade
      CIN (adjusted risk ratio (ARR)=1.52, 95% CI=1.11-2.08; p=0.006) and a
      microinvasive or invasive cancer (ARR=0.56, 95% CI=0.39 0.81; p=0.002).
      CONCLUSION: To ensure that a microinvasive cancer has not been overlooked, the
      excision of high-grade CINs seems to be justified, whatever the clinical status
      and the colposcopic aspect.

PMID- 9197452
TI  - Preoperative evaluation of tumor extension in patients with recurrent cervical
      cancer.
AB  - BACKGROUND: Pelvic exenteration is an option in the treatment of locally
      recurrent cervical cancer. Various preoperative diagnostic procedures in the
      estimation of tumor invasion of the bladder and rectum or lymphonodal involvement
      were evaluated. DESIGN: The sensitivity and specificity of cystoscopy,
      intravenous pyelography, irrigoscopy, rectoscopy, and computed tomography were
      evaluated by comparing the preoperative findings with the histological result as
      the 'golden standards'. RESULTS: In the assessment of bladder invasion the
      sensitivity of cystoscopy, intravenous pyelography and computed tomography was
      22.2%, 55.6% and 55.6%, respectively. The overall sensitivity of the three
      diagnostic procedures was 77.8%. In the assessment of invasion of the rectum
      irrigoscopy, rectoscopy and CT revealed a sensitivity of 33.3%, respectively.
      Only 50% of all cases with tumor infiltration of the rectum showed positive
      results when all three diagnostic procedures were combined. The sensitivity and
      specificity of computed tomography in the diagnosis of lymphonodal involvement
      were 75% and 83.3%, respectively. CONCLUSION: We think that there is an obvious
      necessity for all diagnostic procedures for patient selection prior to pelvic
      exenteration. However, all these investigations are not conclusive but complement
      each other. Prior to pelvic exenteration, critical interpretation of all
      preoperative diagnostic procedures is mandatory, otherwise surgery results in an
      unintended palliative procedure.

PMID- 9197454
TI  - Acute intermittent porphyria precipitated by hyperemesis and metoclopramide
      treatment in pregnancy.

PMID- 9197453
TI  - Estradiol, gonadotropins, and tumor markers in ovarian cyst fluid.
AB  - BACKGROUND: The study was designed to improve the discrimination between
      functional and neoplastic ovarian cysts in order to avoid unnecessary surgery.
      METHODS: Concentrations of tumor markers (CA 125, CEA, CASA, CA 72-4) and
      hormones (estradiol, FSH, LH) in cyst fluid were detected by enzyme immuno- or
      immunoradiometric assays. Wilcoxon test was used to evaluate the correlation of
      cyst fluid markers and histology. RESULTS: One hundred and thirty-eight ovarian
      cyst aspirates were investigated. Seventy-one patients (51.5%) had functional
      cysts whereas 67 (48.5%) had benign (n=59) or malignant (n=8) cystic tumors.
      Statistically significant correlations of CA 125 (p<0.0005) and CASA (p<0.02)
      with neoplastic histology were found. No significant correlation could be
      detected between CA 72-4, CEA, or hormone values and histology. Elevated
      estradiol concentrations are suspicious for functional cysts in premenopausal
      age. Low FSH and LH levels seem to be an indicator for functional cysts in peri-
      and postmenopausal age. CONCLUSIONS: The assessed analytes could not reliably
      distinguish between functional and neoplastic ovarian cysts. Our results indicate
      that CA 125 is a marker for neoplastic histology in a proportion of ovarian
      cysts. The use of FSH and LH in the diagnosis of postmenopausal blastomas needs
      further investigation.

PMID- 9197455
TI  - Idiopathic hypereosinophilic syndrome and pregnancy.

PMID- 9197456
TI  - Listeria monocytogenes-induced liver abscess in pregnancy.

PMID- 9197457
TI  - Bilateral ovarian leiomyoma.

PMID- 9197458
TI  - Leiomyoma as a rare differential diagnosis of Paget's disease of the nipple.

PMID- 9197459
TI  - An ectopic pregnancy embedded in the myometrium of a previous cesarean section
      scar.

PMID- 9197460
TI  - Quantitative analysis of mitochondrial DNA deletion in paraffin embedded muscle
      tissues from patients with KSS and CPEO.
AB  - The percentage of common deletion of mitochondrial DNA (mtDNA) was determined
      quantitatively by a PCR-based, non-radioactive method in DNA extracted from
      formalin-fixed, paraffin-embedded skeletal muscle tissues from two patients with
      Kearns Sayre syndrome (KSS) and one with chronic progressive external
      ophthalmoplegia (CPEO). The method involved PCR cycle titration of wild-type and
      deleted mtDNA in parallel, staining of gel bands with the sensitive fluorescence
      dye SYBR Green I, and quantitation of intensity on a computer screen by the NIH
      image program. We determined 75% and 71% common deletion of mtDNA in the KSS
      patients and 35% in the CPEO patient.

PMID- 9197461
TI  - Evidence for increased hydroxylation of pyrrolidone amino acid residues in the
      cuticle of mature Onchocerca volvulus.
AB  - To determine whether morphologic changes are accompanied by variations in the
      biochemical and antigenic properties of the cuticle of Onchocerca volvulus during
      development, we isolated and compared the 2-mercaptoethanol soluble cuticular
      proteins and the insoluble cuticlin from the predominant life-cycle stages
      occurring in man. SDS-PAGE analysis, before and after digestion with collagenase
      from Achromobacter iophagus, revealed that the polypeptide composition of the 2
      mercaptoethanol-solubilised extracts from adult males and nodular microfilariae
      are quite distinct and that these extracts contained predominantly collagen-like
      proteins. Demonstrated by immunoblotting with a hyper immune patient serum pool
      (n = 107), five strongly reactive antigens with apparent molecular weights of
      126, 68, 43, 37 and 33 kDa were detected in the extracts from adult males, while
      at least eight prominent and several weakly reactive components were detected in
      the extracts from nodular microfilariae. The overall amino acid composition of
      the cuticular extracts from the various stages demonstrates that: (a) the cuticle
      of the adult male stage is rich in glycine, pyrrolidone amino acids, and acidic
      amino acids or their amides, (b) eggshells are particularly poor in proline but
      rich in serine residues (14.5%), (c) nodular microfilariae cuticular extracts are
      poor in proline but rich in valine (9.0%) and lysine (7.3%) and (d)
      hydroxyproline and hydroxylysine are present in the cuticle of adults but absent
      in the juvenile life-cycle stages (nodular microfilariae and eggs). This study
      firstly, indicates that the composition of the cuticle of O. volvulus may thus,
      be quite distinct from one parasite stage to another and secondly, that the
      maturation of the parasite in the human host may be accompanied by the extensive
      hydroxylation of prolyl residues and to a lesser extent of lysyl residues in the
      predominantly collagen-like cuticular proteins.

PMID- 9197462
TI  - Purine nucleotide metabolism: specific aspects in chronic lymphocytic leukemia
      lymphocytes.
AB  - The metabolism of purine nucleotides was studied in human peripheral blood
      lymphocytes from healthy subjects and patients with B-cell chronic lymphocytic
      leukemia. Nucleotide content was determined by HPLC. The rate of de novo
      synthesis of purine nucleotides was measured kinetically by following the
      incorporation of 14C-formate into the nucleotides of a lymphocyte suspension. The
      patterns of the main enzymes involved in purine nucleotide metabolism (those of
      the salvage pathway and catabolism) were estimated by a radiochemical method.
      Although the data expressed in relation to cells and protein showed some
      discrepancies, several common differences were evident in both cases. The main
      differences were an increase in NAD and IMP, a sharp decrease in 5'-nucleotidase
      activities and in total guanylate content and synthesis, and an increase in the
      A/G ratio in lymphocytes of patients with respect to controls. The changes in
      these parameters in CLL indicate an imbalance in purine metabolism and may play a
      specific role in the biology of the leukemia cell. They are also potential
      biochemical markers of lymphoid malignancies and may be useful in chemotherapic
      applications.

PMID- 9197463
TI  - Molecular bases of hexokinase deficiency.
AB  - Hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1; HK) deficiency is a
      rare disease where the predominant clinical effect is nonspherocytic hemolytic
      anemia. We have previously shown that the only patient for which hexokinase
      deficiency has been so far investigated at molecular level is a double
      heterozygote carrying a T1667 --> C substitution on one HK type I allele and a 96
      bp deletion (concerning nucleotides 577 to 672 in the HK cDNA sequence) in the
      other allele. To investigate whether these mutations found in the patient with
      the hexokinase variant referred to as 'HK-Melzo' could be associated with
      hexokinase deficiency, we have expressed in E. coli the wild-type human
      hexokinase type I and two different mutants carrying the T --> C nucleotide
      substitution at position 1667 and the nt 577-672 deletion, respectively. Wild
      type human recombinant hexokinase is expressed in bacterial cells as a soluble
      catalytically active enzyme that, upon purification to homogeneity, exhibited the
      same kinetic properties of human placenta hexokinase type I. Both mutant
      hexokinases were also expressed as soluble recombinant proteins under the same
      conditions, but they showed an impaired catalytic activity with respect to the
      wild-type enzyme. In particular, the T1667 --> C substitution, causing the amino
      acid change from Leu529 to Ser, is responsible for the complete loss of the
      hexokinase catalytic activity, while the 96 bp deletion causes a drastic
      reduction of the hexokinase activity. Taken together, both mutations explain the
      hexokinase deficiency found in the patient with the 'HK-Melzo' variant.

PMID- 9197464
TI  - Chemiluminescence and antioxidant levels during peroxisome proliferation by
      fenofibrate.
AB  - Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to
      mice (0.23% w/w in the diet) during 1-3 weeks and H2O2 and TBARS steady state
      concentrations, liver chemiluminescence and antioxidant levels were measured.
      Administration of fenofibrate during 2 weeks induced an increase of 89% in H2O2
      steady state concentration. Spontaneous chemiluminescence was decreased by 57%
      during fenofibrate treatment, while no significant effect was observed on TBARS
      concentration. Hydroperoxide-initiated chemiluminescence was decreased by 56%
      after 15 days of fenofibrate treatment, probably due to an increase in endogenous
      antioxidant levels. Total and oxidized glutathione increased gradually after
      fenofibrate administration, obtaining maximal increases of 67% and 58%
      respectively, after 22 days of treatment. An increase of 55% was found in
      ubiquinol levels in treated mice, as compared with the controls. alpha-tocopherol
      content was decreased by 51% in the liver of fenofibrate-treated mice. According
      to our findings, the high rate of H2O2 production associated with peroxisome
      proliferation, would not lead to an increase in lipid peroxidation. This can be
      explained by the presence of high levels of ubiquinols, which act as an
      antioxidant. The increased production of H2O2, would lead to DNA damage directly,
      and not through lipid peroxidation processes.

PMID- 9197465
TI  - The human peroxisomal multifunctional protein involved in bile acid synthesis:
      activity measurement, deficiency in Zellweger syndrome and chromosome mapping.
AB  - The dehydrogenation of 24R,25R-varanoyl-CoA, the physiological intermediate
      formed during the peroxisomal breakdown of the bile acid intermediate
      trihydroxycoprostanic acid, was studied in human liver. The reaction appeared to
      be catalyzed by two different enzymes. A first one, present in the cytosol, did
      not discriminate between the four possible varanoyl-CoA isomers and did not
      require the CoA moiety. The second enzymic activity was associated with
      peroxisomes and acted only on the 24R,25R-isomer, in which the 24-hydroxy group
      possesses the D-configuration. The D-specific dehydrogenase is part of a 79 kDa
      protein which represents the human counterpart of a recently discovered second
      multifunctional protein in rat liver peroxisomes, named multifunctional protein 2
      (MFP-2). Human MFP-2, like its rat counterpart, is also responsible for the
      formation (by hydratation) of 24R,25R-varanoyl-CoA. A deficiency of MFP-2 in
      Zellweger liver could be demonstrated immunologically by using antibodies against
      the rat enzyme and enzymically -- after removal of the cytosol -- by using
      24R,25R-varanoyl-CoA. The gene coding for MFP-2 was mapped to chromosome 5q2.3.

PMID- 9197466
TI  - Association of malaria with inactivation of alpha1,3-galactosyl transferase in
      catarrhines.
AB  - Present-day catarrhines (old world monkeys and hominoids) lack Gal alpha1-3 Gal
      beta1-4 GlcNAc-R structures (alpha-galactosyl epitopes) and produce the
      corresponding anti-galactosyl antibodies (anti-gal), while platyrrhines (new
      world monkeys) and non-primate mammals possess alpha-galactosyl epitopes and lack
      anti-gal. Anti-gal is shown to inhibit Plasmodium falciparum growth in culture in
      a concentration dependent manner. probably by binding to alpha-galactosyl
      epitopes on merozoite surface molecules and causing complement mediated damage. A
      P. falciparum-like malaria parasite may therefore have selected for the
      inactivation of an alpha 1-3 galactosyl transferase in catarrhines. The
      implications of the results for the development of clinical immunity to
      falciparum malaria are briefly discussed.

PMID- 9197467
TI  - Lead induced rise in intracellular free calcium is mediated through activation of
      protein kinase C in osteoblastic bone cells.
AB  - Lead characteristically perturbs processes linked to the calcium messenger
      system. This study was undertaken to determine the role of PKC in the Pb2+
      induced rise of [Ca2+]i. [Ca2+]i was measured using the divalent cation
      indicator, 1,2-bis(2-amino-5-fluorophenoxy) ethane N, N,N',N'-tetraacetic acid
      (5F-BAPTA) and 19F-NMR in the osteoblast cell line, ROS 17/2.8. Treatment of
      cells with Pb2+ at 1 and 5 microM produced a rise in [Ca2+]i from a basal level
      of 125 nM to 170 nM and 230 nM, respectively, while treatment with phorbol 12
      myristate 13-acetate (PMA) (10 microM), an activator of PKC, produced a rise in
      [Ca2+]i to 210 nM. Pretreatment with calphostin C, a potent and highly selective
      inhibitor of PKC activation failed to produce a change in basal [Ca2+]i and
      prevented any rise in [Ca2+]i in response to Pb2+. To determine whether Pb2+ acts
      directly on PKC, we measured the Pb2(+)-dependent activation of
      phosphatidylserine/diolein-dependent incorporation of 32P from ATP into histone
      and endogenous TCA precipitable proteins in the 100,000 X g supernatant from
      homogenized ROS 17/2.8 cells. The free concentrations of Pb2+ and Ca2+ were set
      using 5F-BAPTA; and [Ca2+] and [Pb2+] in the PKC reaction mixtures were confirmed
      by 19F-NMR. We found that Pb2+ activates PKC in the range of 10(-11)-10(-7) M,
      with an activation constant of 1.1 X 10(-10) M, whereas Ca2+ activates PKC in the
      range from 10(-8) to 10(-3) M, with an activation constant of 3.6 X 10(-7) M.
      These data suggest that Pb2+ activates PKC in ROS 17/2.8 cells and that Pb2+
      activation of PKC mediates the documented rise in [Ca2+]i and, perhaps, other
      toxic effects of Pb2+.

PMID- 9197468
TI  - The effect of histological processing on the form of iron in iron-loaded human
      tissues.
AB  - Iron-loaded human spleen tissue was immersed in neutral buffered formalin over a
      period of 200 days. Over the first 60 days, iron leached steadily from the tissue
      until 3% had been lost. Thereafter, no further iron leaching was detected.
      Comparisons of Mossbauer spectra of freeze-dried tissue and tissue freeze-dried
      after immersion in formalin for 200 days showed no evidence of chemical
      transformation of the iron remaining in the tissue. The spectra indicated a
      difference in the heme-iron to non-heme iron ratio between the two samples
      probably reflecting inhomogeneity of the ratio throughout the spleen as measured
      on the centimetre scale. Mossbauer spectra of freeze-dried samples of iron-loaded
      human liver and pancreas tissue were compared with those for samples from the
      same patient that had been processed by routine hospital procedures for histology
      and archival. These spectra showed no evidence for chemical transformation of the
      iron present in the tissues. These results demonstrate that it is feasible to use
      archived fixed and embedded human tissue samples for studies aimed at gauging the
      relative fraction of goethite-like hemosiderin present in the tissue.

PMID- 9197469
TI  - Polyunsaturated fat in the diet may improve intestinal function in patients with
      Crohn's disease.
AB  - To investigate the effect of increasing dietary polyunsaturated fat intake on fat
      absorption in Crohn's patients, normal subjects and subjects with inactive
      Crohn's disease consumed a high polyunsaturated to saturated fat ratio diet.
      Subjects participated in breath tests before and after six months of a high
      polyunsaturated to saturated (P/S) fat ratio diet to measure their response to [1
      13C] 10:0 and [1-13C] 16:0 ingested with a test meal. Whole body absorption
      oxidation of C10:0 was not affected by the diet treatment. Before diet treatment,
      whole body absorption-oxidation of C16:0 in Crohn's patients was 80% of that
      observed for control subjects. After consuming a high polyunsaturated to
      saturated fatty acid ratio diet, subjects increased oxidation of C16:0 by 85%
      compared to before the diet treatment period. It is concluded that (1) absorption
      of labelled C16:0 from a test meal is reduced in Crohn's patients, and (2)
      consumption of a high polyunsaturated to saturated fatty acid ratio diet improves
      the utilization of dietary C16:0 by Crohn's patients.

PMID- 9197470
TI  - Failure of muscle energy metabolism in a patient with adenylosuccinate lyase
      deficiency. An in vivo study by phosphorus NMR spectroscopy.
AB  - 31P-nuclear magnetic resonance spectroscopy was used to investigate in vivo the
      energy metabolism of the calf muscle in a 10-year-old patient with
      adenylosuccinate lyase deficiency and severe psychomotor retardation. The patient
      showed a markedly reduced PCr/P(i) molar ratio, known to well represent the
      cytosolic phosphorylation potential, due to low PCr and high P(i) content in
      resting muscle. Moreover, intracellular ATP concentration was significantly lower
      than in the control group both at rest and at the end of post-exercise recovery.
      The rate of patient's PCr recovery after an exercise in ischaemic conditions was
      also out of the reference range, suggesting a reduced ability of mitochondria to
      respond to metabolic needs.

PMID- 9197471
TI  - A mutant cell line resistant to Vibrio parahaemolyticus thermostable direct
      hemolysin (TDH): its potential in identification of putative receptor for TDH.
AB  - Thermostable direct hemolysin (TDH), a pore-forming toxin produced by Vibrio
      parahaemolyticus, is cytotoxic to Rat-1, a fibroblast cell line derived from rat
      embryo. Through mutagenesis of Rat-1 with nitrosoguanidine, we established a
      mutant cell line, MR-T1. MR-T1 was over 200 times more resistant to the cytotoxic
      activity of TDH than Rat-1. TDH increased membrane permeability of Rat-1 but not
      of MR-T1. Binding analysis showed that, while being able to bind to Rat-1. TDH
      failed to bind to MR-T1, indicating that MR-T1 is deficient in the putative
      receptor for TDH. Somatic hybrid cells between Rat-1 and MR-T1 were similarly
      sensitive to TDH as Rat-1. Moreover, TDH could bind to the hybrid cells as well
      as to Rat-1 cells. These results indicate that MR-T1 is promising for
      complementation cloning of a gene related to the putative receptor for TDH.

PMID- 9197472
TI  - Epithelial hyperplastic lesions--a challenging topic in laryngology.
AB  - Adequate diagnosis, treatment and prognosis of particular pathologic entities of
      the laryngeal mucosa depend entirely on the histological changes of the
      epithelium. The basis for the classification of epithelial hyperplastic lesions
      of the larynx (EHLL) is the progression of the histologic features of these
      lesions to cancer. Considering various criteria thought to be typical for the
      transformation of benign EHLL to carcinoma, they are most frequently classified
      into three different groups. However, difficulties begin with the lack of
      uniformity and inconsistency of terminology, and the fact that the
      histomorphological features and biological behavior are not always in accordance.
      It is emphasized that the surface keratosis in laryngeal pathology has no
      prognostic significance per se and that the term risky epithelium should replace
      the expression precancerosis. This term does not predict the evolution of the
      lesion in any way, and it does not exclude any possible future development; but
      it warns the laryngologist to exercise extreme caution and to follow the patient
      closely. Present knowledge of laryngeal cancer, its therapeutic options and
      consequences, force us to pay increasing attention to early detection and
      adequate treatment of EHLL.

PMID- 9197473
TI  - Morphological assessment of malignant potential of epithelial hyperplastic
      lesions.
AB  - The spectrum of conventional and advanced morphological methods for the
      assessment of malignant potential of precancerous lesions of the laryngeal mucosa
      is discussed.

PMID- 9197474
TI  - The Kambic-Gale method of assessment of epithelial hyperplastic lesions of the
      larynx in comparison with the dysplasia grade method.
AB  - Sections of vocal cord biopsies from 47 cases in whom had been previously
      assessed by a dysplasia grading system at from I to III, were reclassified
      according to the Ljubljana system. The majority of the Grade I lesions were
      reclassified as "non-risky", but a small number were put into the risky or even
      carcinoma in situ groups. While most of the Grade III cases were reclassified as
      "risky" there were a few who were assigned to a non-risky category. It is
      suggested that with the Ljubljana histological grading system a more clear-cut
      separation of cases with risk of developing vocal cord malignancy from those with
      no such risk, is possible. Attention is drawn to a lesion denoted as "large cell
      hyperplasia", which is not covered in the grading or Ljubljana categorization of
      vocal cord lesions. The malpighian cells in this lesion are enlarged to over 30
      microm in diameter, and show prominent nucleoli: apoptotic cells are prominent.
      Evidence is presented that this may be a categorical risk for the development of
      malignant changes.

PMID- 9197475
TI  - The role of p53 tumor suppressor gene in human head and neck tumorigenesis.
AB  - Molecular genetics has led to new insights into diagnosis and treatment of human
      cancer. The alterations of tumor suppressor genes like retinoblastoma, p53 and
      others may have an important role in tumorigenesis. Mutations of p53 have been
      found in a majority of human malignancies including head and neck cancer. The
      distribution of p53 is different between types of tumors, suggesting
      environmental exposure as a cause active factor. The p53 mutation in head and
      neck tumors is an early event and appears to have a hot spot region at codons 238
      248. While mutation and loss of heterozygosity at p53 are important in the
      genesis of head and neck cancer, other mechanisms such as binding of viral and
      cellular proteins to p53 are also likely to play a role.

PMID- 9197476
TI  - Apoptosis in epithelial hyperplastic laryngeal lesions.
AB  - The Fas receptor appears to be commonly expressed in all morphological types of
      epithelial laryngeal hyperplasia (HP). Fas-mediated apoptotic cell death would
      thus be a possible phenomenon in these lesions. We observed more anti-apoptotic
      bcl-2 protein in epithelia with simple HP compared to the more advanced types of
      HP. It is suggested that in simple HP there is not yet a need for an early
      selection for cell death. The observed overexpression of metallothionein (MT) in
      the basal layers of simple HP would also support such a theory. These basal cells
      are dividing, non-apoptotic cells, which have not yet been selected for death.
      All 20 cysteine residues in MT are involved in metal binding, interfering with
      the intracellular redox balance, and thereby possibly inhibiting certain
      apoptotic signals. MIB-1 positivity was found only in the atypical HP, CIS, and
      invasive carcinomas. Intuition suggests that high labelling would be associated
      with poor prognosis. The degree of apoptosis, evaluated by TUNEL, did not show
      any differences between different types of epithelia. Although TUNEL is sensitive
      and rather specific, we emphasise that all TUNEL positive cells have apoptotic
      type morphology, confirming good and appropriate use of the technique.

PMID- 9197478
TI  - Molecular biopathology of metaplastic, dysplastic, and neoplastic laryngeal
      epithelium.
AB  - In a large series of more than 100 cases of laryngeal carcinomas, the presence of
      steroid hormone receptors was demonstrated in the cytosol and in the nuclear
      fraction. Their presence was confirmed by the identification of estrogen receptor
      isophorms and by the detection of hormone-related proteins such as ER-D5. EGFr,
      and cathepsin D. These molecules were also variably expressed in normal,
      hyperplastic, and dysplastic epithelium. These data suggest a possible role of
      hormone receptors during laryngeal carcinogenesis. Finally, the presence of an
      Angiotensin II receptor was studied in neoplastic and preneoplastic laryngeal
      epithelium.

PMID- 9197477
TI  - Potential biomarkers in predicting progression of epithelial hyperplastic lesions
      of the larynx.
AB  - Factors contributing to malignant transformation of laryngeal pre-neoplastic
      lesions remain largely unknown. Potential etiologic factors may be related to a
      genetically controlled sensitivity to environmental carcinogens. In this study,
      we investigated bleomycin-induced chromosome fragility in 15 patients with
      laryngeal keratoses who experienced a malignant transformation of pre-neoplastic
      lesions during follow-up, as compared with chromosome fragility in 15 historical
      controls with no progression of laryngeal keratoses during a 10-year follow-up,
      in a match-paired analysis. Chromosomal analysis demonstrated a higher
      sensitivity to clastogens in patients with malignant progression of laryngeal pre
      neoplastic lesions than that of control patients with no evolution of their
      original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify
      possible prognostic markers we studied proliferative activity (MIB-1 expression)
      and p53 gene aberration in biopsy samples from non-invasive and invasive
      laryngeal lesions in both groups. p53 immunostaining was observed in 10/15
      (66.7%) of pre-neoplastic lesions and in 11/15 (73.3%) of metachronous laryngeal
      cancers. No differences in terms of p53 expression were noted between transformed
      and not-transformed lesions. Mutations at p53 gene were observed in 3/15 (20%) of
      pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancers analyzed. Our
      data suggest that p53 alteration is an early event in the genesis of a subset of
      laryngeal carcinomas and that there is no conclusive data about the possible
      clonal development of metachronous laryngeal carcinoma from a p53 mutated pre
      invasive disease in the same patient. MIB-1 expression was found to progressively
      increase with degree of epithelial hyperplasia and dysplasia in both transformed
      (p = 0.007) and not-transformed (p < 0.1) lesions. Surprisingly, pre-invasive
      lesions with tumor evolution showed a lower proliferative activity when compared
      with laryngeal lesions without malignant transformation (p = 0.013). These data
      suggests that subjects with pre-neoplastic laryngeal lesion showing an increased
      susceptibility to carcinogens and with less proliferative disease could be at a
      higher risk for development of laryngeal carcinoma.

PMID- 9197479
TI  - Hyperplastic lesions of the larynx. Experience of the Barcelona group.
AB  - Squamous carcinoma of the larynx arises from pre-existing lesions, the so-called
      "preneoplastic lesions". Hyperplastic lesions represent a part of their spectrum,
      from both clinical and biological points of view. On morphologic grounds, the
      most characteristic feature with prognostic value in the evaluation of
      preneoplastic lesions is dysplasia. It is not only nuclear alterations that are
      seen in the process of malignant transformation, the cytoplasmic pattern of
      cytokeratins changes through neoplastic progression, with a progressive reduction
      of the molecular weight of the produced species. Dysplasia also associates with
      gross alterations of the DNA content. This is in agreement with our finding of
      alterations of genes participating in the control of the cell cycle, p53 and
      p21(WAF1/cip1). p53 overexpression is detected in non-invasive squamous lesions
      (even in the absence of obvious dysplasia) and p21(WAF1/cip1) shows a dramatic
      change in the pattern of expression in dysplastic epithelium compared with the
      normal. However, not all genes participating in the control of the cell cycle are
      altered in early lesions. Overexpression of cyclin D1, a common phenomenon in
      advanced carcinomas, is not likely to participate in the early phases of
      neoplastic development.

PMID- 9197480
TI  - From epithelial dysplasia to squamous carcinoma in the head and neck region: an
      epidemiological assessment.
AB  - The evolution of 97 cases of epithelial dysplasia in the head and neck region was
      retrospectively controlled, with a mean follow-up of 30 months. Dysplastic
      mucosal areas were observed in the oral cavity in 11 cases, in the pharynx (oro-
      and hypopharynx) in 39 cases and in the larynx (supraglottic and glottic regions)
      in 47 cases. According to the criteria defined by the WHO the dysplasia was
      classified as mild, moderate and severe. Fifty out of the 97 patients developed a
      squamous carcinoma in the same area, demonstrating a significant direct
      correlation between age and neoplastic evolution. A direct correlation was also
      observed between severity of dysplasia and carcinomatous evolution. Further
      direct correlations were observed between degree of dysplasia, carcinomatous
      evolution and amount of exposure to cigarette smoke and alcohol.

PMID- 9197481
TI  - From epithelial dysplasia to squamous carcinoma of the head and neck region:
      evolutive and prognostic histopathological markers.
AB  - Ki67 immunoreactivity, p53 expression and apoptotic index were examined in 26 non
      malignant lesions of the head and neck region, 22 dysplastic lesions of patients
      without evidence of head and neck carcinoma during follow-up time, 24 dysplastic
      lesions of patients who subsequently developed a squamous carcinoma in the same
      area, and 42 squamous cancer cases. A directly proportional relation between Ki67
      immunoreactive pattern, apoptotic index and histological evolution from normal to
      dysplastic or neoplastic mucosa was evident. As far as p53 protein is concerned,
      its expression became higher and frequently transmural in neoplastic mucosa. A
      strict correlation between frequency and density of Ki67/p53 immunoreactivity
      according to invasive cell grading (ICG) scores and poor prognosis of patients
      were found. On the contrary, malignant cells highly expressing p53 seemed not to
      undergo apoptosis. Ki67 antigen and p53 protein detection in premalignant lesions
      and in carcinomas of the head and neck tract could be a useful marker for the
      management of patients at risk.

PMID- 9197482
TI  - New aspects in the pathology of the preneoplastic lesions of the larynx.
AB  - In our 5-year biopsy study (1991 95) 51% of keratoses and 16% of adult-onset
      papillomas contained certain degrees of dysplasia. Koilocytosis associated with
      HPV infection was prominent in papillomas and the majority of keratosis but
      negligible in cancer. Using mouse monoclonal antibody against human p53 we
      detected by immunohistochemistry mutated p53 overexpression not only in cancer
      but in some cases of keratoses and papillomas. CD44 is a multifunctional integral
      cell membrane glycoprotein and is found in many mesenchymal, epithelial and tumor
      cells. CD44 has a great number of splice variants, isoforms supposedly implicated
      in development, progression and metastasis formation of tumors. Using monoclonal
      antibody to CD44 our study suggests that the expression of pan CD44 at successive
      stages of human laryngeal carcinogenesis gives preliminary information about the
      selection advantage to the tumor cells.

PMID- 9197483
TI  - Quantitative pathology of laryngeal epithelial hyperplastic lesions.
AB  - We studied 40 laryngeal biopsies samples in order to ascertain the reliability of
      light microscopical criteria for subdividing laryngeal epithelial hyperplastic
      lesions (EHL) and carcinoma in situ as well as to determine the relationship
      between proliferative activity of their epithelial cells and the histological
      grade. The biopsies were divided into four groups in accordance with the Kambic
      Lenart classification: simple, abnormal and atypical hyperplasia and carcinoma in
      situ. 10 cases in each group were included. The morphometrical analysis was
      carried out by a semiautomatic image analysis system. The proliferative activity
      was determined by the high percentage of cell nuclear antigen (PCNA) and Ki-67
      positive epithelial cells and with counting nucleolar organizer regions (Ag-NORs)
      per nucleus. Our results suggest that measuring the nuclear area of the basal
      cells. augmented with basaloid cells and carcinomatous cells, is the most useful
      morphometrical method of differentiating three types of laryngeal EHL and
      carcinoma in situ, while the proliferative activity progressively increased with
      the degree of epithelial hyperplasia. Morphometrical methods and proliferative
      activity should be regarded as useful in conjunction with the traditional
      histopathological methods allowing more of objective grading of EHL.

PMID- 9197484
TI  - Evaluation of DNA content in epithelial hyperplastic lesions of the larynx.
AB  - Quantification of cellular DNA by image or flow cytometry has achieved acceptance
      as an objective and reproducible component of diagnostic pathology. Although the
      majority of investigations have focused on the prognostic utility of DNA content
      measurements in malignant neoplasms, the detection of abnormal DNA content can
      also be useful for the detection of early neoplasia or premalignant change.
      Several studies of laryngeal epithelial hyperplastic lesions by image cytometry
      have shown that a proportion of these lesions exhibit abnormal DNA content and
      that the incidence of this finding correlates with the degree of dysplasia or
      atypia. Similar results were obtained by flow cytometry, which has only rarely
      been used for investigation of these lesions. Although there is some evidence
      that lesions with abnormal DNA content are more likely to progress to carcinoma,
      additional studies are needed to define the clinical importance of DNA cytometry
      in hyperplastic epithelial lesions of the larynx.

PMID- 9197485
TI  - Human papillomaviruses: a study of their prevalence in the epithelial
      hyperplastic lesions of the larynx.
AB  - This study investigated the prevalence of human papillomavirus (HPV) infection in
      various laryngeal epithelial hyperplastic lesions using the Kambic classification
      from simple hyperplasia to invasive squamous cell carcinoma. For detection of HPV
      infection polymerase chain reaction (PCR) with 3 different HPV consensus primer
      sets and in situ hybridization were used. The presence of the HPV DNA was
      detected in only 2 of the 88 specimens tested: HPV type 6 was detected in 1 case
      of simple hyperplasia and HPV type 16 in 1 case of invasive squamous cell
      carcinoma. In conclusion, our study suggests that most laryngeal epithelial
      hyperplastic lesions are not associated with HPV infection and that other
      pathogenic mechanisms are more important in the etiology of these lesions.

PMID- 9197486
TI  - Problems in outpatients with laryngeal hyperplastic lesions.
AB  - The care of outpatients with epithelial hyperplastic lesions of the larynx
      presents problems of classification, treatment, continued surveillance and
      prognosis. One hundred patients who underwent microlaryngoscopy and vocal cord
      stripping from 1990 through 1995 were studied retrospectively with a follow-up
      period of 8-156 months. Twenty-eight patients with biopsy proven epithelial
      hyperplastic lesions were given 21 different pathological diagnoses exclusive of
      invasive carcinoma following 52 operative microlaryngoscopies. Prognosis was
      inferred and treatment commenced primarily on the basis of the pathology report.
      Microlaryngoscopy and stripping with and without the carbon dioxide laser,
      "watchful waiting," radiation therapy, and partial laryngectomy were all used as
      treatment modalities. Controversy remains as of choice of treatment. Encouraging
      the patient to discontinue smoking is an integral part of treatment; however,
      most patients continue to smoke. Recent changes in the United States health care
      delivery system present additional problems in surveillance of the patient.

PMID- 9197487
TI  - Laser surgery of the vocal cord.
AB  - A total of 1032 vocal cord operations have been performed by means of CO2 laser
      in the Department of Otorhinolaryngology, Head and Neck Surgery of the Semmelweis
      University of Medicine in Budapest in the past 10 years. There were 687 benign
      cases and 345 malignant cases of lesions discovered. The procedures were
      performed under general anesthesia in many instances with jet narcosis--in
      laryngomicroscopic exposure. The operations were preceded by careful objective
      diagnostics, such as videolaryngostroboscopy, fiberoscopy, voice analysis,
      airflow and resistance measurements, while the voice and breathing functions were
      monitored postoperatively. Our policy in the therapy of the benign lesions was
      always to use a minimally invasive technique, avoiding damage to the anterior
      commissure, the vocal ligament and the subglottic space. We have experienced a 3
      year survival rate in 87% of the patients with vocal cord carcinomas. According
      to the results of the past 10 years it is proven that the CO2 laser technique is
      an efficient method as well in the surgery of the benign and malignant vocal cord
      lesions, as in the bilateral vocal cord paralysis. Laser surgery might also
      prevent malignant transformation in precancerous vocal cord diseases.

PMID- 9197488
TI  - Epidemiological and clinical relief on hyperplastic lesions of the larynx.
AB  - Chronic hyperplastic laryngopathies are considered precancerous lesions because
      of their possible transformation in time into malignant epithelial neoplasia. We
      studied 130 patients affected by "hyperplastic laryngeal lesions" according to
      their semeiological characteristics. The lesions affected the vocal cords in 127
      cases and in only 3 cases the ventricular bands. All patients underwent
      microlaryngoscopy while under general anesthesia and were treated by limited
      excision (37%) or total stripping (63%). The histomorphological classification by
      Kleinsasser (7) was used. The following clinical checks showed that 30 out of 48
      patients (62.5%) treated by partial stripping recovered; in 11 the lesion
      relapsed (23%) and in 7 cases (14.5%) a carcinoma appeared. Of those cases
      treated by total stripping 65 patients (79%) recovered, 12 (15%) relapsed and 5
      (6%) showed carcinoma. In conclusion we noticed the appearance of a malignant
      lesion after surgery in 12 out of 130 cases (9.2%). The cancerization was about 3
      times more frequent in patients with histological results of degree II than in
      those with degree I (17% vs. 6%). Our study confirms that the laryngeal
      hyperplastic lesion represents a possible passage to cancer in a limited number
      of cases (< 10%), but with a triple probability for degree II dysplasia in
      respect to degree I. The patients affected by dyskeratosis, regardless of type of
      lesion, need a regular follow-up and immediate radical surgery because of the
      frequent incidence of relapse.

PMID- 9197489
TI  - Langerhans and other immunocompetent cells in vocal cord epithelial hyperplastic
      lesions of patients with chronic laryngitis.
AB  - The aim of the study was to evaluate the intraepithelial and stromal density of
      Langerhans cells and lymphoid infiltrate in different stages of carcinogenesis in
      vocal cord biopsies of 24 randomly selected patients with chronic laryngitis. The
      Langerhans and lymphoid cells were counted using immunolabelling with antibodies
      against CD1a, S100, CD3, CD20, and CD68 on paraffin-embedded sections of 24
      archival laryngeal vocal cord mucosa biopsy specimens, 6 classified as simple, 7
      as abnormal, and 11 as atypical epithelial hyperplasia. Results were
      statistically evaluated using the Kruskal-Wallis and Wilcoxon sign rank tests.
      The mean number of Langerhans cells and T lymphocytes per mm2 of cross-sectioned
      epithelium was found to increase from simple to atypical hyperplasia. There were
      statistically significant differences in Langerhans cell density between atypical
      hyperplasia and each of the other 2 grades, simple and abnormal hyperplasia, with
      p < 0.05. Our study suggests the involvement of immune mechanisms, particularly
      cell mediated, during laryngeal carcinogenesis and the possibility that the
      assessment of Langerhans cell density might be of prognostic significance.

PMID- 9197490
TI  - Langerhans cells in human papillomaviruses types 6/11 associated laryngeal
      papillomas.
AB  - Some studies have shown a reduced density of Langerhans cells (LCs) within
      epithelium infected by human papillomaviruses (HPV) types 16/18. However, data on
      a correlation between HPV types 6/11 infection and LCs have been missing. To
      solve this problem, we analysed 24 biopsy specimens of laryngeal papillomas,
      selected randomly, 20 multiple and 4 solitary. The presence of HPV 6 and 11 was
      proven by polymerase chain reaction (PCR) using 2 different sets of primers in 23
      biopsy specimens. Abnormalities of the covering stratified squamous epithelium
      were graded according to the Kambic-Gale classification. LCs were
      immunohistochemically labelled with 2 different antibodies, CD1a and S100.
      Quantitative analysis was performed to determine the density of LC per mm2 in
      different grades of epithelial abnormalities covering laryngeal papillomas.
      Although no statistically significant differences in the mean number of LCs per
      mm2 of the cross-sectioned epithelium covering laryngeal papillomas were observed
      comparing simple, abnormal and atypical hyperplasia groups, the mean number of
      LCs per mm2 in laryngeal papillomas associated with HPV types 6/11 infection
      substantially exceeded that of the vocal cord surface epithelium in patients with
      chronic laryngitis.

PMID- 9197491
TI  - Value of exfoliative cytology in differential diagnosis of epithelial
      hyperplastic lesions of the larynx.
AB  - In a comparative random study we examined material from suspicious laryngeal
      lesions from 85 patients. Material was obtained simultaneously by exfoliative
      cytology and biopsy. The diagnoses included keratosis, papilloma/papillomatosis,
      dysplasia/carcinoma in situ and invasive carcinoma. In each case we were able to
      demonstrate the cytological diagnostic criteria in the respective histological
      specimens. We illustrate this in the paper with some examples. Due to the
      excellent correlation between cytology and histology we are convinced that
      exfoliative laryngeal cytology is very significant in differential diagnosis of
      epithelial hyperplastic lesions.

PMID- 9197492
TI  - Expression of ER-D5 and EGFr in laryngeal carcinoma and pre-malignant epithelium.
AB  - The expression of estrogen receptors was biochemically assessed in a series of 46
      cases of consecutive laryngeal carcinomas. ER-D5 and EGFr were also
      immunohistochemically detected in 44 and 46 cases respectively. There was no
      correlation between the expression of these molecules and the typical anatomo
      clinical prognostic parameters of laryngeal tumors. The concomitant expression of
      estrogen receptors, ER-D5 and EGFr was also investigated in normal, hyperplastic
      and dysplastic epithelium. An increasing expression of ER-D5 and EGFr from normal
      to hyperplastic and dysplastic epithelium was noted. These data suggest a
      possible role of hormone receptors in the laryngeal carcinogenesis.

PMID- 9197493
TI  - Laryngeal papilloma--precancerous condition?
AB  - In a group of 179 patients treated for recurrent laryngeal papillomatosis 668
      surgeries were performed in the years 1982-1995 in the Department of
      Otorhinolaryngology, Head and Neck Surgery in Prague. The group was divided into
      77 patients with a juvenile form of papillomatosis and 102 patients with an adult
      form. The adult form was then divided into a multiple (65 patients) and solitary
      form (37 patients). Three patients with a juvenile form of papillomatosis were
      irradiated in advance. None of these patients developed a carcinoma. There were 3
      cases (1.7%) of carcinoma in the whole group of patients with histologically
      verified papillomas during repeated previous surgeries. All 3 patients with
      malignancy had an adult form of papillomatosis, two with a multiple form and one
      with a solitary form. The intervals between the first treatment for papilloma and
      the diagnosis of carcinoma was 8, 3 and 2 years.The rates of malignant
      transformation of papillomas vary in the literature. We suppose, that because of
      the generally long interval between the diagnosis of papilloma and that of
      carcinoma, to make a final conclusion of a certain ratio is very difficult. We
      envisage that in our group of patients with papillomatosis new cases of carcinoma
      will occur in the future.

PMID- 9197494
TI  - Epithelial hyperplastic lesions of the larynx in biopsy specimens.
AB  - Surgical biopsy files for the period 1991-92 were reviewed to determine the
      relative proportion and types of epithelial hyperplastic lesions of the larynx as
      well as sex and age distribution and correlation between clinical and
      histopathological diagnoses. In this period 203 laryngeal biopsies from 187
      patients were analyzed. Epithelial hyperplastic lesions were found in 42 males
      and 9 females. There were 39 cases with keratosis and 12 cases showing keratosis
      with atypia. Correlation between clinical diagnoses and pathohistological
      findings was established in only 5 cases (9.8%), clinically diagnosed as
      leukoplakia; an additional 5 cases (9.8%) were clinically diagnosed as chronic
      laryngitis. The majority of clinical diagnoses in cases with epithelial
      hyperplastic lesions were laryngeal neoplasm (29, 56.9%) followed by laryngeal
      polyp in 9 cases (17.6%). We conclude that for correct diagnosis the biopsy
      should be performed in all patients with clinical symptoms showing laryngoscopic
      alterations that suggest a potentially malignant lesion.

PMID- 9197495
TI  - Epidermal growth factor receptor, c-erbB-2 and p53 overexpressions in epithelial
      hyperplastic lesions of the larynx.
AB  - An immunohistochemical analysis of overexpression of epidermal growth factor
      receptor (EGFR), c-erbB-2, and p53 proteins was performed on 43 biopsies of
      laryngeal epithelial hyperplastic lesions (EHLL), classified according to the
      Kambic-Lenart classification, and in 11 cases of laryngeal carcinoma (SCCL). The
      aim of the present study was to determine whether there is a correlation between
      the staining patterns of these proteins and different grades of EHLL, and to
      reveal their possible prognostic value. We compared the staining patterns of
      atypical hyperplasia adjacent to cancer with the same type of lesions which have
      not turned malignant. p53 and EGFR overexpressions were detected in 28/54 (52%)
      and 33/54 cases (61%), respectively, and tend to increase with the degree of
      epithelial changes. The intensity of staining in various grades of EHLL adjacent
      to cancer was more pronounced than the same type of lesions which have not
      progressed to cancer. c-erbB-2 was weakly positive in the majority of cases, and
      changed from predominantly membranous in simple hyperplasia to cytoplasmic
      staining in abnormal and atypical hyperplasias. There was no significant
      statistic correlation between the amount of positive cells for all proteins and
      the grade of epithelial abnormalities. We conclude that the overexpression of
      each biomarker itself adds little predictive value over routine histomorphology,
      and cannot be regarded as a reliable prognostic factor for EHLL. However, the
      histologic characteristics of atypical hyperplasia together with the
      immunostaining patterns of EGFR and p53 up to two-thirds or more of the
      epithelial thickness could be considered a reliable pattern which correlates with
      the progression to cancer.

PMID- 9197497
TI  - Our experience with the enhanced polymer one-step staining in frozen sections.
AB  - The enhanced polymer one-step staining (EPOS) method is presented with minor
      modifications for intraoperative frozen sections. It can be applied in almost
      every department of pathology where there is a necessity, because no special
      equipment is required. The method is rapid and immunostaining can be performed in
      less than 15 min. Antibodies are available for more than 20 important tissue and
      tumor markers. Out of those, antibodies against human cytokeratin, leukocyte
      common antigen (LCA) and chromogranin A were introduced in routine work. The
      first 2 antibodies yield excellent results and are a big advantage in routine
      diagnostic work: the use of cytokeratin is useful for confirmation or exclusion
      of suspected tumor invasion, especially in cases of atypical hyperplastic
      lesions, for detection of spindle cell carcinomas, and the detection of lymph
      node micrometastases. LCA demonstration is helpful in differentiating various
      round cell tumors, such as poorly differentiated carcinomas, sarcomas, malignant
      lymphomas, and evaluation of inflammatory response. Chromogranin A may detect
      neuroendocrine differentiation in the tumors.

PMID- 9197496
TI  - Sudden death caused by laryngeal papillomatosis.
AB  - Laryngeal papillomatosis (LP) is the most frequent benign neoplasm of the larynx.
      Clinically it causes hoarseness and upper airway obstruction. Though the LP has
      the potential to endanger life by asphyxiation, this unfortunate outcome is
      extremely rare. We report the case of a 19-year-old female who suddenly died of
      asphyxiation caused by massive LP.

PMID- 9197498
TI  - Correlation of histomorphological criteria used in different classifications of
      epithelial hyperplastic lesions of the larynx.
AB  - Different classifications of epithelial hyperplastic lesions of the larynx were
      proposed, but none of them has been generally accepted. The basic distinction
      among these gradings is evaluation of carcinoma in situ as a precancerosis or a
      distinct and separate entity. In the present study, atypical hyperplasia and
      carcinoma in situ are evaluated according to the proposed histomorphological
      criteria of the Kambic-Lenart classification. In an attempt to separate more
      objectively the histomorphological differences between these 2 lesions, in
      addition to traditional light microscopical examination, we also performed
      semiquantitative analysis with statistical evaluation using the Wilcoxon signed
      rank test. These results revealed a significant morphological and statistical
      difference comparing atypical hyperplasia and carcinoma in situ on the basis of
      the following criteria: abnormal mitotic figures (p = 0.005), mitotic activity (p
      = 0.014), nuclear pleomorphism (p = 0.006), cellular atypia (p = 0.005),
      dyskeratosis (p = 0.008), and stromal infiltration (p = 0.015). These results
      confirm our view that atypical hyperplasia and carcinoma in situ are 2
      consecutive but different entities in the process of carcinonogenesis.

PMID- 9197499
TI  - Human papillomavirus infection and expression of p53 and c-erbB-2 protein in
      laryngeal papillomas.
AB  - Laryngeal papilloma (LP) is the most frequent benign laryngeal epithelial tumor
      caused by human papillomaviruses (HPV) types 6 and 11. In the present study, we
      were interested in whether we can find any prognostic markers which might reflect
      the biological behavior of the covering epithelium in LP. We focused our
      attention on the determination of HPV infection, the detection of p53 protein,
      and c-erbB-2 protein in 24 biopsy specimens of LP. We confirmed the HPV 6 and 11
      etiology in 23 of 24 LP. In these lesions the overexpression of p53 protein
      increased with the grade of epithelial abnormalities. The distribution of
      positive cells changed from scattered and focal, in simple and abnormal
      hyperplasia, to diffuse in atypical hyperplasia. It has been shown that in the
      presence of HPV types 6 and 11 found in LP, p53 can still preserve its tumor
      suppressor activity. Infection with HPV types 6 and 11 might therefore account
      for the significantly lower rate of malignant transformation in LP. Two staining
      patterns for c-erbB-2 protein were observed in the hyperplastic epithelium
      covering LP: membranous and cytoplasmic. With the increasing grade of epithelial
      abnormalities, cytoplasmic staining became predominant, and c-erbB-2 positivity
      sometimes occupied the whole epithelial thickness. This may represent either an
      alteration in the processing stability of the c-erbB-2 mRNA, gene amplification,
      or even an artefact.

PMID- 9197500
TI  - Laser induced fluorescence in diagnostics of laryngeal cancer.
AB  - Differences in autofluorescence between normal and malignant tissues offer new
      possibilities for detecting and localizing early laryngeal carcinomas. In the
      present study imaging was performed using a specially designed device that
      exploits differences in fluorescent properties of normal and cancerous tissues
      without photodynamic drugs. Fluorescence was induced by helium-cadmium laser,
      captured by an image-intensified camera and displayed on a video monitor after
      previous computerization. 40 patients were evaluated, of whom 20 had suspect
      malignancies. Laryngoscopic appearances during standard microlaryngoscopy,
      fluorescence images and computerized fluorescence intensities were compared to
      histopathological findings. The experience from this study shows that
      autofluorescence laryngoscopy may be a useful complementary method for detecting
      laryngeal malignancies.

PMID- 9197501
TI  - Adjuvant therapy with hydrolytic enzymes in recurrent laryngeal papillomatosis.
AB  - The subject of this study is systemic enzymotherapy as adjuvant treatment in
      recurrent laryngeal papillomatosis. The authors analyze their observations of 5
      adult patients with recurrent laryngeal papillomatosis when after surgical
      extirpation and subsequent application of peroral proteases there was a
      significant improvement of their clinical state and laboratory results. The
      patients have been disease-free from 10 to 18 months. In the authors' experience,
      the adjuvant enzymotherapy seems to be a suitable replacement of the
      supplementary treatment in larynx papillomatosis, and it promises to decrease the
      recurrence rate as well.

PMID- 9197502
TI  - Correlation between instability of fundamental voice frequency and malignant
      infiltration of vocal fold nerve endings.
AB  - Performing systematically acoustical objective voice analysis in patients with
      chronic chorditis and glottic cancer we detected a certain number of cases with
      exceptional acoustical pattern. In 7 of 50 patients with chronic chorditis this
      acoustical pattern was highly specific demonstrating frequent changes of
      fundamental frequency in short time interval. In 31 of 50 patients with glottic
      cancer the same phenomenon was recorded. Histology revealed in 6 of those 7
      patients with clinical diagnosis of chronic chorditis invasive cancer of the
      vocal fold. Detailed and more sophisticated techniques (PAF Halmi for elastic and
      collagen fibres and neurohistochemical technique S-100 and NSE for nerve
      elements) demonstrated mainly preserved layer structure of vocal fold lamina
      propria and infiltrated nerve endings. Such histological findings strongly
      suggest that cancer infiltration is responsible for rapid changes of fundamental
      frequency (via mucosal reflexes) although vibratory segments are regular because
      of preserved layer structure. Such findings could contribute to better
      understanding of laryngeal control mechanisms and laryngeal mucosal reflexes in
      human. Also this acoustical sign may be a useful diagnostical parameter for very
      early diagnosis of glottic cancer. This is possible because of the great
      sensitivity and complexity of phonatory function.

PMID- 9197503
TI  - The role of allergy in the etiopathogenesis of laryngeal mucosal lesions.
AB  - The results of this study showed that allergy is an important factor in the
      etiopathogenesis of laryngeal mucosal lesions. Despite adequate treatment, no
      other unfavourable factors appeared to have significant influence on the results
      of the treatment. It seems that hypersensitivity to different inhalatory and
      nutritional allergens make laryngeal mucosa more susceptible for adverse action
      of other factors: vocal misuse, gastroesophageal reflux (GER), smoking, irritants
      in the surrounding microclimate, endocrinologic disorders, etc. Acting together,
      all these factors cause the development of laryngeal mucosal lesions. In the
      treatment of noninfectious laryngitis, vocal cord nodules, polyps or Reinke's
      edema, all the stated adverse factors should be identified and suitably
      diminished or eliminated. Allergy (Ig-E-mediated and non-IgE-mediated) should be
      considered as only one of the etiopathogenetic factors.

PMID- 9197504
TI  - Histology of laryngeal mucosa.
AB  - The larynx is a complex tubular segment of the respiratory system formed by
      irregularly shaped plates of hyaline and elastic cartilage. The mucosa form two
      pairs of folds, false and true vocal cords, which extend into the lumen of the
      larynx. The laryngeal epithelium corresponding to the mechanically exposed areas
      consists of stratified squamous nonkeratinized epithelium. Suprabasally in this
      epithelium, dendritic antigen-presenting Langerhans cells (LCs) can be found. In
      the rest of the larynx, the epithelium is ciliated columnar pseudostratified with
      a rich population of goblet cells. Except in the true vocal cords, lamina propria
      consists of rather loose connective tissue and contains groups of small, branched
      tubuloalveolar glands.

PMID- 9197505
TI  - The interpretation of leukoplakia in laryngeal pathology.
AB  - Leukoplakia is only a descriptive clinical term designating a white patch or
      plaque of the mucosa and must be complemented by histology. On the other hand,
      keratosis is an exclusively histological term denoting pathological production
      and accumulation of keratin on the surface of the laryngeal epithelium.
      Leukoplakia is usually keratosis, but not always. Keratosis can mask various
      epithelial changes, from simple hyperplasia to invasive squamous carcinoma and is
      only the superficially visible manifestation of an underlying pathological
      process. Keratosis means total replacement of superficial epithelial cells by
      keratin filaments, and dissolution of the nuclei. When nuclei are retained in
      keratinized cells, the process is termed parakeratosis. Therefore, keratosis can
      be classified as a separate entity only when histopathological examination
      reveals superficial keratotic changes accompanying a normal squamous epithelium.
      To identify the presence of keratosis in various benign laryngeal entities
      divided according to severity of epithelial abnormalities, and to determine
      whether keratosis has any prognostic value, we performed a retrospective analysis
      on bioptic material on 4,291 tissue specimens over a period of 15 years. Our
      results suggest that keratosis must be considered as only one sign of the
      disorder within the complex of other pathological changes and not as a distinct
      pathological entity. For this very reason, keratinization of the epithelial
      surface was not included among significant parameters used for the grading of
      epithelial changes into the particular group according to Kambic-Lenart
      classification.

PMID- 9197506
TI  - Search for prognostic factors in head and neck cancer.
AB  - Fifteen patients with head and neck carcinoma were treated with irradiation (14
      70 Gy telecobalt). Apoptotic and mitotic index, DNA index, ratio of cells in S
      phase, p53 protein overexpression in untreated tumours as well as the changes of
      these parameters after the first 2 Gy irradiation except proliferative kinetics
      parameters were examined in order to determine the prognostic value of these
      factors. The data show that inducibility of apoptosis is very low in head and
      neck carcinomas which correlate with the unfavourable prognosis. The decrease in
      mitotic index after the first 2 Gy irradiation, which occurred in 7 cases--5 of
      them still alive--indicates a better chance for relatively longer survival. In
      immunohistochemically p53 positive tumours frequently occurring aneuploidy and
      elevated S-phase rate were found.

PMID- 9197507
TI  - The usefulness of screening in the early detection of laryngeal cancer.
AB  - Opinions are divided about screening for cancer in the early stage and for
      hyperplastic alterations of the laryngeal mucosa which may lead to cancer. In
      order to form our own opinion we conducted a laryngological survey of 100 male
      and 50 female patients aged 30-70, employed in the textile and metallurgical
      industry, most of whom were smokers. In no case did we detect cancer or any
      abnormalities that would require immediate additional diagnostic procedures. We
      are well aware that caution is required in the analysis of data obtained in a
      sample as small as ours. Nevertheless we were to find even in this small group at
      risk, at least a few patients with laryngeal mucosa which could progress into
      cancer, yet we did not detect such changes. For this reason we concluded that
      screening does not always result in the hoped for outcome. It also requires much
      time and effort. We even question the justification of yearly examinations of the
      populations at risk, even though some authors consider this to be feasible. More
      important than screening is public health education which is primarily the
      responsibility of general practitioners as well as laryngologists. The population
      has to be educated and made to understand that surgery or radiation therapy at
      early stage of cancer is almost totally curable and does not result in any
      mutilation or invalidity.

PMID- 9197508
TI  - The role of general practitioner in the detection of epithelial hyperplastic
      lesions and carcinoma of the larynx.
AB  - The present study deals with the approach of 78 general practitioners (GPs) in
      south-eastern Slovenia (mainly in Dolenjska region with population of 234,000) to
      patients with symptoms of laryngeal disease in the period 1990-95. Only 2 of the
      GPs (2.6%) examined the larynx of such patients with a laryngeal mirror, while
      the remainder failed to perform a larynx examination. None of the GPs had a rigid
      90 degrees telescope. General practitioners usually treated their patients with
      laryngeal complaints by antibiotic therapy, and in some cases also by
      inhalations. Patients with persistent laryngeal symptoms were referred to an
      otorhinolaryngologist. We have also established who (the patient, GP,
      otorhinolaryngologist) and to what extent was responsible for the delay at
      diagnosis of laryngeal cancer, and determined how many months had lapsed from
      initial symptoms to the first check-up with a GP. Our analysis has shown that in
      23 patients (20%) laryngeal cancer was detected in an advanced stage due to a
      prolonged and incorrect treatment administered by a GP. Patients with cancer of
      the glottis delayed their visit to their GP for 2 months on average, while in
      those with cancer of the supraglottis and subglottis this delay was 6 months. In
      carcinoma of the glottis, the average delay from the onset of first symptoms to
      diagnosis was 3 months, while in the case of carcinoma of the supraglottis and
      subglottis this delay was even longer than 7 months. The patients with carcinoma
      of the supraglottis and subglottis were given 2 months of antibiotic treatment by
      a GP without having the diagnosis established. We believe that the GP could
      contribute significantly towards earlier diagnosis of hyperplastic changes of the
      laryngeal mucosa, which can lead to cancer transformation, as well as to
      laryngeal cancer detection at an early stage. This could be achieved in the
      following ways: GPs should examine the patients' larynx by indirect laryngoscopy.
      In the case where they are not adequately qualified or equipped to perform the
      examination, they should refer them to an otorhinolaryngologist in due time. A
      much greater proportion of patients with symptoms of laryngeal disease would have
      appeared for the examination sooner, had the general population been offered
      regular and sufficient health education by GPs.

PMID- 9197509
TI  - T1-T2-T3 glottic tumors: fifteen years experience with CO2 laser.
AB  - This research aims at reporting the results of endoscopic treatment of glottic
      carcinomas by CO2 laser. The cases cited concern 516 patients with glottic T1-T2
      T3 carcinomas. The patients have been divided into 5 groups: a) T1a: 194 patients
      with monolateral carcinoma involving the true vocal cord who underwent simple
      cordectomy; b) T2a: 104 patients with monolateral cordal carcinoma involving the
      ventricle and the false cord; c) T1b: 127 cases of monolateral or bilateral
      carcinoma involving the anterior commissure; d) these patients underwent
      bilateral cordectomy; T2b: 54 cases of monolateral or bilateral carcinomas
      involving the anterior commissure and extending to the hypoglottic or
      supraglottic region; in these patients a bilateral extended cordectomy was
      performed; e) T3: 37 selected cases of monolateral or bilateral cordal carcinoma
      with fixed vocal cord, fixity was due to the substantial size of the tumor or to
      the infiltration of the paraglottic space; these patients underwent a monolateral
      or bilateral extended cordectomy. The following are the results at 5 years: group
      a: overall observed survival rate (OSR) was 79% and the adjusted survival rate
      (ASR) 94.5%; group b: OSR 67% and ASR 77%; group c: OSR 88.4% and ASR 96.5%;
      group d: OSR 82% and ASR 90%; group e: OSR 55% and ASR 67%. The above data are
      evidence of the fact that our surgical techniques offer similar or better
      advantages in terms of survival rate compared to the traditional procedures. It
      must be noted that endoscopic surgery of glottic tumors carried out by CO2 laser
      offers relevant benefits when compared with traditional surgery: i) rapidity of
      operation and reduced surgical trauma; ii) the possibility of avoiding
      tracheotomy; iii) the respect of the integrity of the cartilaginous skeleton; iv)
      short postoperative course and low incidence of complication; v) better
      functional results; vi) a shorter stay in hospital with positive psychological
      effects on the patients and lower social costs.

PMID- 9197510
TI  - Epidemiology of laryngeal cancer: results of the Heidelberg case-control study.
AB  - Squamous cell carcinoma of the larynx is a multifactorial disease which
      predominantly is found in males aged 50-70 years. Chronic consumption of alcohol
      and tobacco independently increase the relative risk of this type of cancer in a
      dose-dependent manner. Low educational standards and occupational training are
      associated with high risk. The majority of the cancer patients are blue collar
      workers who are exposed to a variety of hazardous working materials like
      polycylic aromatic hydrocarbons, cement dust, metal dusts, asbestos, varnish,
      lacquer, etc. Environmental exposure to airborne carcinogens like fossil fuel
      single stove emissions may increase the relative risk of laryngeal cancer. The
      regular consumption of fruit, salad and dairy products which contain considerable
      amounts of tumor protective micronutrients may decrease the risk of laryngeal
      cancer.

PMID- 9197511
TI  - Stroboscopic observation of the larynx after radiation in patients with T1
      glottic carcinoma.
AB  - We studied laryngeal video stroboscopy (LVS) system for evaluation of patients
      with glottic carcinoma (T1N0M0) before and after radiotherapy. There were 10
      patients with T1 glottic squamous cell carcinoma (9 men and 1 woman) who received
      radiotherapy at the Hitachi General Hospital. We performed LVS before and after
      radiotherapy. The presence or absence of mucosal waves (MW) was particularly
      noted. No MW were present before radiotherapy but at 1-6 months after, MW
      gradually appeared. One year after radiotherapy all patients showed MW on LVS. In
      patients with glottic carcinoma MW recovered after radiation therapy. LVS may be
      useful for the clinical follow-up of post-radiation patients for early detection
      of recurrence of glottic carcinoma.

PMID- 9197512
TI  - Bronchopulmonary changes after laryngeal cancer treatment--differentiation
      between metastatic laryngeal and second primary cancer.
AB  - The survivors of laryngeal cancer have an increased risk of second primary
      cancer, especially in the lung. Therefore, the authors were interested, if there
      is an increase of precancerous lesions or malignancies in bronchopulmonary
      biopsies of the patients after laryngeal cancer treatment. There were 70 (38
      transbronchial and 32 bronchial) of 5,097 bronchopulmonary biopsies in 58
      patients (55 men and 3 women) with history of laryngeal carcinoma. The age of the
      patients ranged from 39 to 81 years (mean value 62.5 years). The biopsies were
      performed from 1 month to 23 years after surgical treatment and/or radiation
      therapy due to squamous laryngeal carcinoma. The frequency of metaplastic,
      dysplastic and tumorous lesions was contrary to expectation a bit lower than in
      routine bronchial biopsies. But in contrast with the latter, metastases were 10
      times more common among tumorous lesions. In 19 of 58 patients malignancies
      appeared from 1 month up to 276 months after laryngectomy. Four patients had
      definitively, and another 5 very probably second primary carcinoma. Ten patients
      presented with metastases from laryngeal cancer. The possibilities to
      differentiate metastatic laryngeal and second primary carcinoma are discussed.

PMID- 9197513
TI  - Old/new differences in direct and indirect memory tests using pictures and words
      in within- and cross-form conditions: event-related potential and behavioral
      measures.
AB  - Indirect measures of repetition priming are more sensitive to changes in surface
      features than are direct measures of memory. This dissociation may reflect
      differences in the extent to which the two tasks rely on form-specific processes,
      or on the activation of different memory systems. To assess this, subjects at
      study made semantic discriminations to a mixed list of pictures and words. At
      test, half the concepts were repeated in the surface form presented at study
      while half were repeated in the other surface form. Subjects in the indirect test
      continued making the same discrimination, whereas those in the direct test
      performed a yes/no recognition task. For both tasks, significant old/new within
      form differences were found for event-related potential (ERP) and reaction time
      (RT) measures. Cross-form old/new differences were reliable only for the word
      picture condition in the direct task and only for the ERP indices. These data
      suggest that both direct and indirect memory tasks are influenced by form
      specific as well as form-non-specific processing, and that neither the transfer
      appropriate processing nor memory systems approaches can completely account for
      this pattern of results.

PMID- 9197514
TI  - Time to detect the difference between two images presented side by side.
AB  - The time to locate a difference between two artificial images presented side by
      side on a CRT screen was studied as a function of their complexity. The images
      were square lattices of black or white squares or quadrangles, in some cases
      delineated by a blue grid. Each pair differed at a single position, chosen at
      random. For images of size N x N, the median reaction time varied as cN2, from N
      = 3-15, with c being around 50 ms in the absence of grid (i.e., when the
      quadrangles were associated into continuous shapes). For N < or = 9, when the
      lattice was made irregular, performance did not deteriorate, up to a rather high
      level of irregularity. Furthermore, the presence of uncorrelated distortions in
      the left and right images did not affect performance for N < or = 6. In the
      presence of a grid, the reaction times were on average higher by 20%. The results
      taken together indicate that the detection of differences does not proceed on a
      point-by-point basis and must be mediated by some abstract shape analysis, in
      agreement with current views on short-term visual memory (e.g., Phillips, W.A.,
      On the distinction between sensory storage and short-term visual memory, Percept.
      Psychophys., 16 (1974) 283-290 [13]). In complementary experiments, the subjects
      had to judge whether two images presented side by side were the same or
      different, with N varying from 1 to 5. For N < 3, the same and the different
      responses were similar in all their statistical aspects. For N > or = 4, the
      "same" responses took a significantly larger time than the "different" responses
      and were accompanied by a significant increase in errors. The qualitative change
      from N = 3 to N = 4 is interpreted as a shift from a "single inspection" analysis
      to an obligatory scanning procedure. On the whole, we suggest that visual
      information in our simultaneous comparison task is extracted by chunks of about
      12 +/- 3 bits, and that the visual processing and matching tasks take about 50 ms
      per couple of quadrangles. In Section 4, we compare these values to the values
      obtained through other experimental paradigms.

PMID- 9197515
TI  - Commonality of processes underlying visual and verbal recognition memory.
AB  - Memory for visual and verbal material engages widely distributed systems, to a
      large degree focussed in different hemispheres. It might thus be expected that
      these disparate neuronal populations should display significantly different
      characteristics in regard to mnemonic performance. Visual memory, fundamental to
      all human beings, and whose characteristics are largely shared with macaques, was
      assayed using unique non-objective, colored images lacking ready verbal
      description and was contrasted with memory for four-letter non-offensive English
      words. The effects of memory loading, stimulus duration and long-term test
      intervals (1-2 weeks) were studied in regard to accuracy and reaction times for
      recognizing initial versus re-exposure to these two types of items. No effects of
      memory loading were apparent despite the incrementing memory load in the 240
      item, running recognition sessions. Words were better remembered than images,
      both in the long and short term, but the detailed characteristics of reaction
      times and accuracy in relation to number of intervening items, and in long-term
      memory were strikingly similar. Given the wide and well-established disparity in
      cerebral loci participating in linguistic versus image analysis, these multiple
      similarities in the pattern of mnemonic performance indicate that the underlying
      neuronal processes must be comparable for remembering either images or words.
      Furthermore, the strong link manifested between individual items across a varying
      number of intervening intervals and added items suggests that a phenomenon highly
      similar to the "stimulus specific adaptation" (SSA), displayed by units in
      macaque inferotemporal cortex, occurs for each item to be recognized. Finally,
      the significant augmentation in accuracy both in short- and long-term memory for
      images when viewing time permits saccades is explained if each saccade and
      fixational pause recruits additional neurons into the pool displaying SSA, or its
      equivalent, for the item being viewed.

PMID- 9197516
TI  - Relative alpha desynchronization and synchronization during speech perception.
AB  - Brain processes elicited by speech were studied in 10 right-handed subjects by
      means of examining the desynchronization and synchronization of the 8-10 Hz and
      10-12 Hz EEG alpha frequency bands. The subjects listened to an auditorily
      presented 5 min text passage. The text was presented both forward and backward.
      Listening to the text forward elicited alpha desynchronization in both of the
      frequency bands studied, whereas listening to the same text presented backward
      elicited synchronization in the 10-12 Hz frequency band only. Listening to the
      text forward elicited greater desynchronization than listening to the text
      backward. In the 10-12 Hz frequency band, listening to the text forward elicited
      desynchronization whereas listening to the same text backward elicited
      synchronization. This dissociation was not observed in the 8-10 Hz frequency
      band. The results suggest that the lower and upper alpha bands differ such that
      the 10-12 Hz frequency band exhibits reactivity to the presence of linguistic
      content while the 8-10 Hz band shows an unspecific response.

PMID- 9197517
TI  - Auditory evoked potentials in young patients with Down syndrome. Event-related
      potentials (P3) and histaminergic system.
AB  - Subjects with Down syndrome exhibit various types of cognitive impairment.
      Besides abnormalities in a number of neurotransmitter systems (e.g. cholinergic),
      histaminergic deficits have recently been identified. Brainstem auditory evoked
      potentials (BAEPs) and auditory event-related potentials (ERPs), were recorded
      from 10 children (aged 11-20 years) with Down syndrome and from 10 age- and sex
      matched healthy control subjects. In Down subjects, BAEPs revealed shortened
      latencies for peaks III and V with shortened interpeak latencies I-III and I-V.
      ERPs showed a delay of components N1, P2, N2 and P3. In addition, subjects with
      Down syndrome failed to show P3 amplitude reduction during repeated stimulation.
      To evaluate the cognitive effects of histaminergic dysfunction, ERPs were
      recorded from 12 healthy adults (aged 20-28 years) before and after
      antihistaminergic intervention (pheniramine) compared to placebo. Whereas
      components N1, P2, N2 remained unchanged after H1-receptor antagonism, P3 latency
      increased and P3 amplitude showed no habituation in response to repeated
      stimulation. The results suggest that the characteristic neurofunctional
      abnormalities present in children with Down syndrome must be the consequence of a
      combination of structural and neurochemical aberrations. The second finding was
      that antihistaminergic treatment affects information processing tested by ERPs
      similar to that seen with anticholinergic treatment.

PMID- 9197518
TI  - Administration of DL-2-amino-5-phosphonovaleric acid (AP5) induces transient
      inhibition of reminder-activated memory retrieval in day-old chicks.
AB  - DL-2-Amino-5-phosphonovaleric acid (50 microM) administered immediately after a
      visual reminder presented to day-old chickens between 7.5 min and 24 h following
      a single trial passive avoidance learning task produced transient losses of
      memory on retention test, an effect not observed in the absence of a reminder or
      when the reminder was given 48 h post learning. The duration of the transient
      deficits decreased with increasing interval between training and the reminder
      trial. The time of onset of memory loss after the reminder trial appeared to
      increase with increasing interval between the training and the reminder trials.
      The results suggest that, for a period of at least up to 24 h after passive
      avoidance training, retrieval of memory may lead to processes which are sensitive
      to inhibition by the NMDA receptor antagonist AP5, with the duration of
      sensitivity post retrieval decreasing as the period of memory consolidation
      increases. The results extend previously reported findings and suggest the
      possibility that consolidation of a stable memorial representation of a learning
      experience may take over several days and may entail the concurrent laying down
      of a stable retrieval mechanism.

PMID- 9197519
TI  - Integration of somatosensory and vestibular inputs in perceiving the direction of
      passive whole-body motion.
AB  - We investigated the contribution of somatosensory and vestibular inputs in the
      detection of the direction of linear whole-body displacement (1.5 m) at low
      levels of linear acceleration (peak acceleration 0.2 m/s2), in normal subjects.
      Subjects sat on a mobile robot wearing opaque goggles and headphones. They
      indicated the direction of motion by using a laser pointer held by the right hand
      at the level of the chin. Adaptation to a long-lasting static head turn (45
      degrees to the right) was used to modify the perceived head orientation relative
      to the trunk. After about 15 min the head and trunk were perceived to be aligned
      with each other. After adaptation subjects pointed in the same direction as in
      the control condition in spite of the change in the perception of the head
      orientation. Because space orientated reactions to vestibular stimuli were
      previously shown to be coded in the perceived head reference frame, these results
      indicate that somatosensory cues are also integrated in the perception of linear
      motion. Unexpectedly, after adaptation, trunk and head perceived orientations
      were attracted toward the direction of the imposed motion. This suggests that the
      internal representation of body configuration depends also upon available cues
      from the extrapersonal space.

PMID- 9197520
TI  - Blind rats are not profoundly impaired in the reference memory Morris water maze
      and cannot be clearly discriminated from rats with cognitive deficits in the cued
      platform task.
AB  - The Morris water maze is commonly used to test cognitive function in rodent
      models of neurological disorders including age-related cognitive deficits. It is
      often assumed that the most profoundly impaired aged rats may be blind due to
      retinal degeneration, and it has been reported that animals with visual sensory
      deficits can be identified based on their performance in a cued platform task.
      The results of the present study demonstrate that blind rats can perform
      surprisingly well in the reference memory version of the Morris water maze, and
      that blind rats cannot be selectively excluded based on performance in the cued
      platform task since atropine-treated rats also perform poorly in the cued
      platform task. Future studies may be able to develop screening procedures that
      help to eliminate subjects with non-cognitive deficits, but the present results
      do not support the use of the cued platform or straight swim task as screening
      procedures. Experimenters must be careful to consider the role that visual
      sensory function and other non-cognitive factors may have in performance of the
      spatial learning Morris water maze, and also the role that severe cognitive
      deficits may have in performance of the cued platform task.

PMID- 9197521
TI  - Environmental mutagens and the fundamental concept of the cause of human cancer
      (1997 Japan Prize).

PMID- 9197522
TI  - Analysis of the DPC4 gene in gastric carcinoma.
AB  - Allelic loss on chromosome 18q is involved in the progression of gastric
      carcinoma. Recently, DPC4 (deleted in pancreatic carcinoma, locus 4), a candidate
      tumor suppressor gene, has been localized at 18q21.1. This gene is inactivated in
      nearly one half of pancreatic carcinomas. We tested for DPC4 gene mutations and
      allelic status at 18q21 in 30 primary gastric carcinomas and 5 gastric carcinoma
      cell lines. Polymerase chain reaction single-strand conformation polymorphism and
      sequencing analyses revealed no DPC4 mutations in any of the primary tumors or
      cell lines. Homozygous deletion of DPC4 was observed in only 1 (MKN-45) of the 5
      (20%) cell lines. This suggests that the target gene for loss on 18q is not DPC4.
      The true tumor suppressor gene, encoded near DPC4, has yet to be identified.

PMID- 9197523
TI  - MAD-related genes on 18q21.1, Smad2 and Smad4, are altered infrequently in
      esophageal squamous cell carcinoma.
AB  - The MAD (mothers against decapentaplegic)-related genes, Smad2 (former name MADR2
      or JV18-1) and Smad4 (former name DPC4), have been identified on chromosome
      18q21.1. We analyzed 30 primary esophageal squamous cell carcinomas (ESCC) and 7
      cell lines derived from ESCC for intragenic mutations and loss of heterozygosity
      (LOH) of the Smad2 and Smad4 genes. LOH was detected in 5 of 14 (35%) informative
      cases. However, no mutations in either gene were detected in either the primary
      carcinomas or the cell lines, and only a G-to-A base transition within the 3'
      untranslated region of the Smad4 gene was observed in a carcinoma. There were no
      homozygous deletions in either of the genes in the cell lines. MAD-related genes
      on chromosome 18q21.1 are altered infrequently in ESCC.

PMID- 9197524
TI  - A randomized controlled trial for chemoprevention of gastric cancer in high-risk
      Japanese population; study design, feasibility and protocol modification.
AB  - We have initiated a population-based, double-blind, randomized controlled trial
      to examine the effects of supplementation of beta-carotene and vitamin C on the
      incidence of gastric cancer. The subjects were participants in an annual health
      screening program conducted by four municipalities in Akita prefecture, one of
      the regions with the highest mortality from gastric cancer in Japan. We measured
      their serum levels of pepsinogens (PGs) I and II, and asked persons diagnosed
      with chronic atrophic gastritis (defined as PG I < 70 ng/ml and PG I/PG II ratio
      < 3.0) to take diet supplements containing 0 or 15 mg/day beta-carotene and 50 or
      500 mg/day vitamin C for 5 years. During the first year of recruitment conducted
      in one village from June through September, 1995, 52% (635/1214) of screening
      participants had chronic atrophic gastritis and 73% (439/602) of eligible persons
      responded. However, in response to a National Cancer Institute press report
      released on January 18, 1996, indicating that two beta-carotene trials had shown
      no benefit and potential harm from the supplement, we discontinued the beta
      carotene and continued with the trial using only vitamin C. Of 397 participants
      remaining at this point, 77% (305) consented to stay in the study. The results
      indicate that a randomized controlled trial for cancer prevention is feasible in
      the Japanese asymptomatic population.

PMID- 9197525
TI  - Decrease of prostaglandin E2 and 5-bromo-2'-deoxyuridine labeling but not
      prostate tumor development by indomethacin treatment of rats given 3,2'-dimethyl
      4-aminobiphenyl and testosterone propionate.
AB  - The modifying effects of indomethacin (IM) on rat prostate carcinogenesis induced
      by 3,2'-dimethyl-4-aminobiphenyl (DMAB) were investigated. F344 rats were given
      50 mg/kg body weight of DMAB at 2-week intervals for 20 weeks and then received
      IM at a dose of 20 ppm in the drinking water for 37 weeks. Separate groups
      additionally received testosterone propionate (TP) in Silastic tubes throughout
      the experiment. DMAB alone induced carcinomas in situ in the ventral lobe and in
      combination with TP caused invasive carcinomas of the dorso-lateral and anterior
      lobes and seminal vesicles. No clear suppression by IM of development of in situ
      carcinomas or invasive carcinomas was observed. In a short-term satellite
      experiment, it was revealed that prostaglandin E2 (PGE2) levels in the dorso
      lateral prostate and seminal vesicles, but not the ventral prostate, were
      significantly reduced by IM and that TP itself also suppressed PGE2 levels. The 5
      bromo-2'-deoxyuridine labeling index in the ventral prostate was significantly
      decreased by IM administration. These results indicate that while IM can
      efficiently suppress tissue PGE2 levels, it does not inhibit tumor development in
      the prostate or seminal vesicles of rats in the present model.

PMID- 9197526
TI  - Inhibition by green tea extract of diethylnitrosamine-initiated but not choline
      deficient, L-amino acid-defined diet-associated development of putative
      preneoplastic, glutathione S-transferase placental form-positive lesions in rat
      liver.
AB  - The effects of green tea extract (GTE) on exogenous and endogenous models of rat
      liver carcinogenesis using diethylnitrosamine (DEN) and a choline-deficient, L
      amino acid-defined (CDAA) diet were studied. For the exogenous carcinogenesis
      study, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal
      dose of 200 mg/kg body weight of DEN, partially hepatectomized at week 3, and
      administered GTE at doses of 0, 0.01 and 0.1% in the drinking water from week 2
      for 10 weeks. For the endogenous carcinogenesis study, rats were fed the CDAA
      diet and simultaneously given GTE for 12 weeks. All rats were killed at the end
      of week 12. After DEN-initiation, the apparent numbers of glutathione S
      transferase placental form-positive foci, assayed as putative preneoplastic
      lesions, were decreased by the administration of GTE, though their sizes were not
      altered. In contrast, GTE did not significantly reduce the numbers of the lesions
      induced by the CDAA diet or affect their sizes. While the levels of 8
      hydroxyguanine, a parameter of oxidative DNA damage, were reduced by the GTE
      administration in both experimental models, GTE did not protect against the CDAA
      diet-associated liver tissue damage in terms of either histology or plasma marker
      enzyme levels. We conclude that, while GTE may be a possible chemopreventive
      agent for nitrosamine-initiated hepatocarcinogenesis in the absence of chronic
      hepatocyte damage, it does not significantly inhibit lesion development in
      hepatocarcinogenesis associated with the CDAA diet, a cirrhosis-associated model.

PMID- 9197527
TI  - Rare occurrence of ras and p53 gene mutations in mouse stomach tumors induced by
      N-methyl-N-nitrosourea.
AB  - The incidence of point mutations of H-, K- and N-ras and p53 oncogenes in male
      BALB/c mouse stomach tumors induced with N-methyl-N-nitrosourea (MNU) was
      examined by direct sequencing and PCR single-strand conformation polymorphism
      (PCR-SSCP). A mutation of GGT to AGT at K-ras codon 12 was found by SSCP in one
      adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9
      adenomatous hyperplastic regions, 1 squamous cell carcinoma and 4 normal-like
      stomach regions from 4 mice. No mutations were detected by direct sequencing of H
      , K- and N-ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a
      total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatous hyperplastic
      regions, 2 squamous cell carcinomas and 4 normal-like stomach regions from 6
      mice. No mutations were detected by direct sequencing of p53 oncogene at exons 5,
      6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous
      hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal-like
      stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do
      not play a role in mouse stomach carcinogenesis induced by MNU.

PMID- 9197528
TI  - Antibodies to human papillomavirus 16, 18, 58, and 6b major capsid proteins among
      Japanese females.
AB  - Among genital human papillomaviruses (HPVs), the so-called high-risk (HPV 16, 18,
      etc.) and intermediate-risk (HPV 58, etc.) viruses are believed to be
      etiologically associated with cervical cancer. To estimate the extent of
      infection with common HPVs among Japanese females, we examined 328 sera from
      healthy donors (201) and patients with cervical intraepithelial neoplasia (CIN)
      (22), cervical cancer (67), and condyloma acuminatum (CA) (38) for IgG antibodies
      against L1 capsid protein by enzyme-linked immunosorbent assay using virus-like
      particles of HPVs 16, 18, 58 and 6b (low-risk) as antigens. Antibodies
      recognizing conformational epitopes were found in the sera from both the patients
      and the healthy donors. The prevalences of anti-HPV 16, 18, and 58 antibodies in
      the sera from the patients with CIN (45%) and cervical cancer (49%), and that of
      anti-HPV 6b in the sera from the patients with CA (55%), were significantly
      higher than those in the sera from the age-matched healthy donors (12%, 14%, and
      23%, respectively). Anti-HPV 16 was not found in some of the sera from patients
      with HPV 16-DNA positive CIN or cervical cancer, suggesting that HPV infection
      may not always induce production of anti-capsid antibodies or that the level of
      antibodies may not always be maintained until development of CIN or cancer. Some
      of the sera contained antibodies against more than one type of HPV, suggesting
      that the donors had been infected with different HPVs. The type-specific
      antibodies against capsid L1 protein of one type of HPV may not be able to
      prevent infections with other types of HPVs.

PMID- 9197529
TI  - Human papillomavirus infection and risk determinants for squamous intraepithelial
      lesion and cervical cancer in Japan.
AB  - A case control design was used to investigate human papillomavirus (HPV)
      prevalence and risk factors associated with development of cervical squamous
      intraepithelial lesion (SIL) and cervical cancer (CC) in Japan. One hundred and
      twenty-three women with histologically confirmed SIL or CC were compared to a
      control group of 778 cytologically normal women. With the use of a polymerase
      chain reaction (PCR)-based method for detection of low-risk (types 6 and 11) and
      high-risk (types 16, 18, 31, 33, 35, 52 and 58) HPVs, a high prevalence of HPV
      infection was observed in smokers among the controls. Logistic regression
      analysis demonstrated that high-risk HPV infection was the most significant risk
      determinant for LSIL (OR=9.4, 95% CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC
      (OR=97, 95% CI=35-269). It also showed that unmarried women, women married for 5
      to 19 years and smokers represented high risk groups for SIL, while smokers and
      women with a history of many pregnancies/parities had increased risk for CC.
      Smoking was the only HPV infection-independent factor for CC, suggesting that
      smoking may have a carcinogenic effect on the cervix. Since neither history of
      other cancer nor family cancer history was associated with SIL or CC, genetic
      factors appear to play little role in cervical carcinogenesis. The risk for
      cervical neoplasia due to HPV infection increased after marriage in Japan,
      suggesting a role for husbands as carriers of HPV transmission. Protection from
      high-risk HPV infection may be of greatest importance for prevention of cervical
      cancer.

PMID- 9197530
TI  - Alternative splicing of the FHIT gene in colorectal cancers.
AB  - In the present study, we examined the status of the FHIT gene in 112 colorectal
      cancer and 137 colorectal adenoma specimens. In a total of 5 specimens (4
      colorectal cancers and 1 colorectal adenoma), a common smaller product was
      detected in addition to the normal size product. This smaller product had lost
      exon 4, the 5' noncoding region of the FHIT gene, owing to alternative splicing.
      Moreover, all of the 5 tumors with alternative splicing were located lower on the
      rectum than the anterior peritoneal reflection.

PMID- 9197531
TI  - PRLTS gene alterations in human prostate cancer.
AB  - Since loss of heterozygosity on 8p22-p21.3 has been found frequently in prostate
      cancer, the status of a candidate tumor suppressor gene named PRLTS gene,
      recently cloned from the same region in some human malignancies, was examined in
      the present study. DNAs were isolated from 69 Japanese prostate cancer patients
      (37 localized and 32 cancer-death cases). Loss of heterozygosity at this gene
      locus was observed in 15 of 36 (42%) localized prostate cancer patients and 22 of
      32 (69%) cancer-death patients. One cancer-death patient had a missense mutation,
      ACG-->ATG (Thr-->Met) at codon 64 in metastatic tumor tissues of pelvic lymph
      node and liver, and these tissues showed loss of the homologous allele,
      indicating that "two-hit" mutation of the PRLTS gene had occurred in this case.
      The others did not show any mutation, regardless of the presence or absence of
      loss of heterozygosity. Although loss of heterozygosity at the PRLTS gene locus
      is a relatively common abnormality, mutation of this gene is rare in prostate
      cancer.

PMID- 9197534
TI  - Mutational analysis of BRCA1 gene in ovarian and breast-ovarian cancer families
      in Japan.
AB  - We analyzed the alteration of BRCA1 in DNA obtained from 83 individuals of 13
      Japanese site-specific ovarian cancer families and 6 breast-ovarian cancer
      families. Six germline mutations were detected in 7 families, which consisted of
      4 breast-ovarian cancer and 3 site-specific ovarian cancer families, by single
      strand conformation polymorphism analysis, followed by direct sequence
      determination. The mutations included three frameshifts, two nonsense mutations,
      and one missense mutation causing loss of a zinc-binding motif. The frequency of
      loss of heterozygosity at the microsatellite markers on the BRCA1 gene was 57% (8
      of 14 cases) in site-specific ovarian cancer families, and 100% (6 of 6 cases) in
      breast-ovarian cancer families. All tumors of the patients carrying a mutation of
      BRCA1 showed deletion of wild-type alleles, implicating BRCA1 as a tumor
      suppressor gene. These results suggest that germline mutations of the BRCA1 gene
      play an important role in the carcinogenesis of breast and/or ovarian cancer in a
      majority of breast-ovarian cancer families and in some site-specific ovarian
      cancer families.

PMID- 9197532
TI  - Two transcription factors, E1AF and N-myc, correlate with the invasiveness of
      neuroblastoma cell lines.
AB  - The ets transcription factor E1AF can activate several matrix-degrading
      metalloproteinase (MMP) genes and is implicated in enhancement of tumor cell
      invasion. Here we compared the invasive activity of five human neuroblastoma cell
      lines (TGW, GOTO, SK-N-BE, SK-N-SH and SK-N-AS), which exhibit distinct levels of
      N-myc amplification, together with the expression of E1AF. Extracellular matrix
      degrading proteases and their inhibitor proteins, which play an important role in
      local invasion, were also analyzed. The activity to invade through reconstituted
      basement membrane was high in cells (TGW, GOTO, and SK-N-BE) with N-myc
      amplification, and these cells produced relatively large amounts of E1AF mRNA,
      correlating with the invasive activities. Of several matrix metalloproteinases
      (MMPs) and a tissue inhibitor of MMPs (TIMP), only membrane-bound type 1 MMP (MT1
      MMP) was specifically detected in N-myc-amplified cells, suggesting a role of MT1
      MMP in neuroblastoma cell invasion. MMP-2 (72 kD type IV collagenase), TIMP-1 and
      TIMP-2 were expressed in all five cell lines. Urokinase-type plasminogen
      activator was undetectable. These findings indicate that the transcription
      factors E1AF and N-myc are related to malignant phenotypes of neuroblastoma.

PMID- 9197535
TI  - Detection of MAGE-4 protein in sera of lung cancer patients.
AB  - We investigated the level of MAGE-4 protein in sera of patients with primary lung
      cancer to understand better the biological roles of the MAGE proteins. MAGE-4
      protein was detected as a non-degraded form in both the supernatant of a MAGE-4+
      tumor cell line and in a patient's serum. Serum level of the MAGE-4 protein in
      lung cancer patients (n=100, mean=1.17 ng/ml) was significantly higher than that
      in either patients with benign pulmonary diseases (n=80, 0.33 ng/ml) or healthy
      donors (n=68, 0.32 ng/ml). It was higher than the cutoff level (1.15 ng/ml) in 34
      of 100 cancer patients, but not in anyone in the other groups.

PMID- 9197533
TI  - Expression of interstitial collagenase (matrix metalloproteinase-1) in gastric
      cancers.
AB  - The expression of matrix metalloproteinase-1 (MMP-1) gene and the presence of MMP
      1 protein in gastric cancer were examined by in situ hybridization and
      immunohistochemistry. Expression of the interstitial collagenase (MMP-1) gene was
      detected within the stroma of the neoplastic glands, and infiltration of
      eosinophils was observed to be associated with regions of MMP-1 gene expression.
      The degree of eosinophilic infiltration correlated with the level of MMP-1 mRNA
      expression. Immunostaining showed localization of MMP-1 protein in the stromal
      cells, and additionally in the neoplastic glands. These findings indicate that
      the stromal cells may play an important role in the expression of MMP-1, and
      suggest a pathophysiological role for MMP-1 in the invasion and metastasis of
      gastric cancer.

PMID- 9197536
TI  - Detection of residual host cells in sex-mismatched bone marrow transplantation in
      various hematological diseases by fluorescence in situ hybridization.
AB  - Thirty-eight sex-mismatched bone marrow transplantation patients with various
      hematological diseases were followed-up using fluorescence in situ hybridization.
      Probes specific for various translocations, the X chromosome (DXZ1) and the whole
      Y chromosome (WCP Y), were used to assess successful engraftment and residual
      host cells. The combination of translocation and WCP Y probes enabled the
      identification of host and donor cells in addition to the identification of
      malignant vs. normal cells in the transplant recipient. Fifteen patients were
      sequentially followed up. The results obtained using the combination of
      translocation plus WCP Y probes were more reliable than those with DXZ1 plus WCP
      Y probes, or the translocation probe alone, especially when the percentage of
      residual leukemic cells detected by the translocation probe alone was around the
      cut-off level.

PMID- 9197537
TI  - Radioimmunodetection with 111In-labeled monoclonal antibody Nd2 in patients with
      pancreatic cancer.
AB  - This report summarizes results from an initial clinical evaluation of
      radioimmunodetection (RAID) in patients with pancreatic cancer using murine
      monoclonal antibody Nd2, directed against mucins from pancreatic cancer. Nd2 (2
      mg) was labeled with 111In (2 mCi) and injected into 19 patients suspected of
      having pancreatic cancer. Planar scintigrams were taken 3 days post-infusion. As
      for final diagnoses after surgery, 14 cases were pancreatic cancer, and one case
      each was chronic pancreatitis, neurilemmoma, islet cell carcinoma, cholangioma,
      and apparent absence of suspected recurrent lesion of pancreatic cancer. Of 14
      patients with pancreatic cancer, RAID was positive in 10 cases (71.4%). Cases
      other than pancreatic cancer were all negative, so the specificity was 100%.
      These results demonstrate that RAID using 111In-Nd2 can be useful in
      differentiating exocrine pancreatic cancer from benign conditions and other types
      of carcinomas in the pancreatoduodenal regions.

PMID- 9197538
TI  - Analysis of an expression profile of genes in the human adipose tissue.
AB  - Increasing evidence suggests that in addition to storing excess energy as fat,
      adipose tissue acts as an endocrine organ secreting various factors into the
      blood stream. Every time a new factor is found in adipose tissue, however, its
      implication is discussed independently, and a systematic analyses based upon a
      global view of gene expression of this tissue has not been performed. To describe
      the function of this tissue in terms of gene expression, and to find new factors,
      we performed random complementary DNA (cDNA) sequencing using a 3'-directed cDNA
      library that faithfully represents the composition of the messenger RNA (mRNA).
      Various well-known but unexpected genes, including those for gelsolin, plasma
      glutathione peroxidase (GPX-3) and carboxypeptidase E (CPE) were shown to be very
      active. By comparing the expression profile of active genes in the adipose with
      those of other tissues and with data in dbEST, we identified seven new genes that
      are specifically expressed in adipose tissue. Among these, one encoded a protein
      with collagen-like repeats and a putative secretion signal. These data can be
      used as new tools for analyses of the physiology of this tissue, as well as the
      etiology and complications of obesity.

PMID- 9197539
TI  - Chlorella virus SC-1A encodes at least five functional and one nonfunctional DNA
      methyltransferases.
AB  - Chlorella virus SC-1A encodes at least six DNA methyltransferases (MTases): four
      N6-methyldeoxyadenine (m6A) MTases, M x CviSI (TGCmA), M x CviSII (CmATG), M x
      CviSIII (TCGmA) and M x CviSIV (GmATC), one 5-methyldeoxycytosine (m5C) MTase, M
      x CviSV (approximately RCmCG), and one nonfunctional m5C MTase, M x CviSVI, which
      is homologous to the MTase M x CviJI [RGmC(T/C/G)] produced by another chlorella
      virus IL-3A. Genes encoding three of the SC-1A m6A MTases (M x CviSI, M x CviSII,
      and M x CviSIII) and the nonfunctional m5C MTase were cloned and sequenced.
      Neither M x CviSI nor M x CviSIII genes hybridized to genes for their respective
      isomethylomers, M x CviRI and M x CviBIII, from other chlorella viruses. However,
      the M x CviSII gene hybridized strongly to its M x CviAII isomethylomer gene from
      virus PBCV-1. Like the prototype chlorella virus PBCV-1, the SC-1A genome
      contains inverted terminal repeats, one of which is adjacent to the nonfunctional
      m5C MTase. The three cloned m6A MTase genes are distributed throughout the
      approx. 345 kb SC-1A genome.

PMID- 9197540
TI  - Identification of an acetolactate synthase small subunit gene in two eukaryotes.
AB  - Acetolactate synthase catalyses the first step in branched-chain amino acid
      biosynthesis. The bacterial enzyme contains two large and two small subunits but
      there is only limited and circumstantial evidence for a small subunit in the
      eukaryotic enzyme. Here this evidence is summarised and protein sequences of two
      putative eukaryotic small subunits, from a yeast and a red alga, are presented.

PMID- 9197541
TI  - Cloning and characterization of mouse Lmp3 cDNA, encoding a proteasome beta
      subunit.
AB  - We isolated and sequenced a cDNA encoding mouse proteasome subunit LMP3 from a
      macrophage cDNA library. The gene encodes a 264-amino-acid protein with a
      calculated molecular mass of 29.11 kDa and an isoelectric point (pI) of 5.44.
      Comparison of the predicted protein sequence with that of the human and rat
      homologues, N3, revealed 11 and eight changes, respectively, in the cleaved NH2
      terminal presequence of the precursor protein (pre-LMP3), and six and 10 changes,
      respectively, in the processed product. To corroborate the predicted molecular
      mass and pI, we analyzed LMP3 by immunoprecipitation with a mAb to human N3 that
      crossreacts with mouse LMP3. Precursor and processed forms of LMP3 were
      identified by 2D NEPHGE-PAGE, and their mobilities suggest the Lmp3 clone encodes
      the entire protein sequence.

PMID- 9197542
TI  - Cloning and characterization of a dextranase gene (dexS) from Streptococcus suis.
AB  - A gene (dexS) coding for a Streptococcus suis capsular type 2 dextranase (DexS)
      was detected in a recombinant gene library constructed in phage lambda ZapII, and
      its nucleotide sequence was determined. Sequence comparison showed that the dexS
      gene product had significant similarities with enzymes which hydrolyze glucose
      polymers. Moreover, conserved amino acids that are suggested to be part of the
      active site of the glucosidases are also found in DexS. The dexS gene, adjacent
      to the gene encoding a S. suis IgG-binding protein, encoded a protein of
      approximately 62 kDa which exhibited DexS activity.

PMID- 9197543
TI  - Isolation and characterization of the Neisseria meningitidis lpxD-fabZ-lpxA gene
      cluster involved in lipid A biosynthesis.
AB  - The lpxD-fabZ-lpxA gene cluster involved in lipid A biosynthesis in Neisseria
      meningitidis has been cloned and sequenced. By complementation of a temperature
      sensitive E. coli lpxD mutant, we first cloned a meningococcal chromosomal
      fragment that carries the lpxD homologue. Cloning and sequence analysis of
      chromosomal DNA downstream of lpxD revealed the presence of the fabZ and lpxA
      genes. This gene cluster shows high homology to the corresponding genes from
      several other bacterial species. The LpxA and LpxD proteins catalyze early steps
      in the lipid A biosynthetic pathway, adding the O- and N-linked 3-OH fatty acyl
      chains, respectively. In E. coli and N. meningitidis, LpxD has the same
      specificity, in both cases adding 3-OH myristoyl chains; in contrast to E. coli,
      the meningococcal LpxA protein is presumed to add 3-OH lauroyl chains instead.
      The established sequence points the way to further experiments to define the
      basis for this difference in specificity, and should allow modification of
      meningococcal lipid A biosynthesis through gene exchange.

PMID- 9197544
TI  - Genomic organization and characterization of the gene encoding bovine
      prostaglandin F2alpha receptor.
AB  - We isolated genomic clones for bovine prostaglandin (PG) F2alpha receptor by the
      standard plaque hybridization method, using the cDNA fragments of bovine
      PGF2alpha receptor (PGF2alphaR) as probe DNAs. The coding regions of this
      receptor gene were interspersed by a large intron sequence (33 kb) at the splice
      junction in the sixth transmembrane domain. The 5'-RACE experiments revealed two
      alternative transcription start points (tsp), indicating the existence of two
      potential promoter regions. The major promoter, which was named promoter region
      A, was located upstream of exon 1 and lacked the typical TATA sequence and CAAT
      box but had three GC boxes with an overall high GC content. Another putative
      promoter, region B, was found upstream of exon 2 and had both a TATA-like
      sequence and a CAAT-like box with several potential binding sites for
      transcription factors. Southern blot analysis indicated that a single copy gene
      in the haploid genome encodes PGF2alphaR. Promoter activities of these two
      putative promoter regions were assayed in the bovine luteal cells, and one of
      them (promoter region A) was activated by phorbol 12-myristate 13-acetate (TPA)
      treatment.

PMID- 9197545
TI  - Sequence and expression analysis of a Xenopus laevis cDNA which encodes a
      homologue of mammalian 14-3-3 zeta protein.
AB  - We report the cloning and characterisation of a cDNA that encodes a novel member
      of the Xenopus laevis 14-3-3 protein family. Sequence analysis reveals that the
      cDNA-encoded protein shares 84% identity with the rat, human or sheep 14-3-3zeta
      isoform, and between 66% and 77% identity with bovine, human or rat beta, bovine
      gamma, human tau, Drosophila 14-3-3 and a previously isolated Xenopus member. The
      corresponding mRNA is present in all adult tissues examined with the highest
      levels in the brain. Although the gene is expressed throughout embryogenesis,
      higher levels of mRNA accumulate after gastrulation. Whole-mount in situ
      hybridisation on tailbud stage embryo reveals strong expression of the gene in
      the head, optic vesicles, spinal cord and branchial arches with weaker expression
      in the somites. In addition, expression along the notochord is observed at stage
      45 (tadpole). This spatial and temporal expression profile along with recent
      studies implicating the importance of 14-3-3 proteins in the regulation of signal
      transduction pathways argues for a key role of this isoform in embryonic
      development.

PMID- 9197546
TI  - Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin conjugating
      enzyme: hUbc9.
AB  - Poly(ADP-ribose) polymerase (PARP) has been suggested to play a regulatory role
      in vivo, in DNA replication and/or DNA repair based mainly on its capacity to
      bind to DNA strand breaks. This interaction is modulated through auto poly(ADP
      ribosylation). However, the biological function of PARP may also involve
      interactions with proteins such as topoisomerase I or DNA polymerase alpha, which
      may or may not be themselves ADP-ribosylated. Using the yeast two-hybrid method
      search for other proteins interacting with PARP, we have isolated a full-length
      cDNA clone coding for a protein of 158 amino acid residues. This amino acid
      sequence is 66 and 56% identical to yeast ubiquitin-conjugating enzymes Hus5 and
      Ubc9 of Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively.
      Moreover, we have demonstrated that the expressed protein complements a S.
      cerevisiae yeast strain deficient for Ubc9. The protein encoded by the isolated
      cDNA is thus a new human counterpart of the ubiquitin-conjugating enzyme family
      and has been called hUbc9. The hubc9 gene locus has been assigned to the
      chromosomal location 16p13.2-p13.3. By means of two-hybrid analysis it was
      discovered that hUbc9 interacts with the automodification domain of PARP. This
      interaction was further confirmed using GST (glutathione-S-transferase) tagged
      fusion proteins: (i) in vivo, by transfecting cos7 cells with hUbc9 cloned in an
      eukaryotic expression vector, and (ii) in vitro, by mixing purified PARP with
      hUbc9 purified and expressed in bacteria. The possible significance and function
      of this interaction is discussed while taking into account the possible
      intracellular role of hUbc9.

PMID- 9197547
TI  - The avian C/EBPgamma gene encodes a highly conserved leucine zipper transcription
      factor.
AB  - The C/EBP family of transcription factors regulates viral and cellular
      CCAAT/enhancer element-mediated transcription. We report the isolation and
      characterization of genomic and cDNA clones encoding avian CCAAT/enhancer-binding
      protein-gamma (C/EBP gamma). A partial cDNA clone for a C/EBP-related gene was
      previously identified by expression library screening for proteins binding the A1
      CCAAT/enhancer motif from the avian leukosis virus long terminal repeat [W.
      Bowers and A. Ruddell (1992) J. Virol. 66, 6578-6586]. Additional cDNA and
      genomic clones were generated and sequenced to identify the complete protein
      coding sequence of this gene. Sequence analysis indicates that this gene encodes
      the avian homolog of C/EBP gamma. As with the murine C/EBP gamma homolog, the
      avian C/EBP gamma gene is comprised of two exons, with the open reading frame
      encoded in exon 2. The 150-aa C/EBP gamma protein is highly conserved, as the
      avian protein shows more than 80% identity with the murine and human homologs.
      The sequence of the initiation methionine (-3 caaAUGa +4) from the 150-aa open
      reading frame has a non-optimal Kozak initiation sequence. In vitro transcription
      and translation assay of this avian cDNA followed by radioimmunoprecipitation
      assay using a murine C/EBP gamma antiserum indicates that this non-optimal
      initiation codon is used to express a 22-kDa DNA-binding protein.

PMID- 9197548
TI  - Purification and cDNA cloning of maize HMGd reveal a novel plant chromosomal HMG
      box protein with sequence similarity to HMGa.
AB  - We have purified the chromosomal high mobility group (HMG) protein HMGd from
      maize suspension culture cells, determined the N-terminal amino acid (aa)
      sequence, and isolated the corresponding cDNA. Sequence analysis showed that the
      cDNA encoded a protein of 126 aa residues with a theoretical mass of 14,104 Da.
      The protein contains an HMG-box DNA-binding domain and a short acidic C-terminal
      tail. HMGd is in approx. 65% of its residues identical to maize HMGa, whereas it
      is only approx. 46% identical to maize HMGcl/2. The differences to the previously
      reported HMG proteins in aa sequence, in overall charge and in protein size
      indicate that we have identified a third type of plant chromosomal HMG-box
      protein belonging to the HMG1 protein family. Immunoblot analysis with a HMGd
      antiserum reveals that HMGd is expressed in all tissues tested.

PMID- 9197549
TI  - Alternative splicing in lecithin:cholesterol acyltransferase mRNA: an
      evolutionary paradigm in humans and great apes.
AB  - Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting
      reverse cholesterol transport, is expressed in liver and cultured fibroblasts.
      Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products.
      In addition to the normal transcript, we identified an alternate message with a
      splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and
      6. In humans, the alternate transcript represents 5-20% of the complete LCAT
      message in cultured fibroblasts and liver. It is present in humans and the great
      apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old
      or new world monkeys). Sequencing of intron 5 of the LCAT locus in several
      primates revealed a G-->A transition at the splice donor recognition site in the
      Alu repeat of the gibbon and a G-->A substitution in the last position of the 95
      bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions
      have been associated with exon skipping in other genes. These results demonstrate
      that alternative splicing of LCAT mRNA is variant among primates and suggest a
      potential role of Alu elements in the evolutionary diversity of proteins.

PMID- 9197550
TI  - Antibiotic resistance gene cassettes derived from the omega interposon for use in
      E. coli and Streptomyces.
AB  - Three antibiotic resistance gene cassettes, derived from the omega interposon
      (Prentki and Krisch (1984) Gene 29, 303-313) were constructed. These cassettes
      carry different antibiotic resistance genes, conferring resistance to geneticin,
      hygromycin or viomycin, flanked by short inverted repeats containing
      transcription and translation termination signals and synthetic polylinkers.
      These cassettes were designated omega aac, omega hyg and omega vph. Resistance
      phenotypes conferred by these constructions are selectable in E. coli and
      Streptomyces. These cassettes can be used for insertional mutagenesis or for
      vector construction.

PMID- 9197551
TI  - RNA secondary structure as a reusable interface to biological information
      resources.
AB  - The dissemination of biological information has become critically dependent on
      the Internet and World Wide Web (WWW), which enable distributed access to
      information in a platform independent manner. The mode of interaction between
      biologists and on-line information resources, however, has been mostly limited to
      simple interface technologies such has hypertext links, tables and forms. The
      introduction of platform-independent runtime environments facilitates the
      development of more sophisticated WWW-based user interfaces. Until recently, most
      such interfaces have been tightly coupled to the underlying computation engines,
      and not separated as reusable components. We believe that many subdisciplines of
      biology have intuitive and familiar graphical representations of knowledge that
      can serve as multipurpose user interface elements. We call such graphical idioms
      "domain graphics". In order to illustrate the power of such graphics, we have
      built a reusable interface based on the standard two dimensional (2D) layout of
      RNA secondary structure. The interface can be used to represent any pre-computed
      layout of RNA, and takes as a parameters the sets of actions to be performed as a
      user interacts with the interface. It can provide to any associated application
      program information about the base, helix, or subsequence selected by the user.
      We show the versatility of this interface by using it as a special purpose
      interface to BLAST, Medline and the RNA MFOLD search/compute engines. These
      demonstrations are available at: http://www-smi.stanford.edu/projects/helix/pubs/
      gene-combis-96/

PMID- 9197552
TI  - Epithelial wound healing of the rat cornea after excimer laser ablation.
AB  - Rats with excimer corneal ablations (ArF 193 nm, 228 pulses, diameter 3,5 mm,
      17.3 mJ per pulse, depth about 1/2 of corneal thickness) in one eye were killed
      1, 2, 4, 6 and 13 days after treatment. The other eye served as control. The cell
      number per microscopic vision field, the labelling index (LI) and the mitotic
      rate (MR) were calculated for the peripheral, midperipheral and central areas of
      the corneal epithelium. The cell number showed a uniform depression in the
      remaining corneal epithelium at Day 1, normalizing from the centre to the
      periphery. The LI was only significantly increased at Day 1, while the MR was
      statistically significantly increased peripherally at Day 2 and in all areas at
      Day 6. However, when the corneal epithelium was evaluated as a whole, the MR was
      significantly increased at days 1, 2 and 6. The proliferative response of the
      epithelium was very homogenous irregardless of the distance to the original
      lesion. Both the migratory and the proliferative phases of the healing process
      seemed to be delayed when compared to the healing of pure epithelial wounds.
      However, the initiation of an increase in DNA synthesis seems not to be delayed,
      indicating that it is primarily the G2 phase that has been prolonged with this
      ablation procedure. The stromal thickness was increased from about one half of
      the normal values immediately after the treatment to above normal values at Day
      4, thereafter decreasing to normal values at Day 13. Thus, the regenerative
      ability of the stroma is more pronounced in rats than in humans, but also in
      humans regeneration of the stroma can possibly explain the regression of the
      myopic shift seen some time after excimer laser treatment.

PMID- 9197553
TI  - UVB-induced formation of (6-4) photoproducts in the rat corneal epithelium.
AB  - The induction of DNA photoproducts in rat corneal epithelium was studied after in
      vivo exposure to different doses of ultraviolet B light at 297 nm. Affinity
      purified antibodies with a major specificity against UV-induced (6-4)
      photoproducts were used. The results indicate a dose dependent formation of (6-4)
      photoproducts. Even a minimal erythema dose (25 mJ/cm2) produced (6-4)
      photoproducts, demonstrating that DNA damage occurs in corneal tissue following
      exposure to biologically relevant doses of UVB light.

PMID- 9197554
TI  - Fluence and mutagenic side effects of excimer laser radiation applied in
      ophthalmology in human lymphocytes in vitro.
AB  - PURPOSE: To investigate the influence of different fluences in 193 and 248 nm
      excimer laser radiation on the yields of chromatid and chromosome aberrations
      induced in human lymphocytes in vitro. METHOD: Heparinized human blood was
      exposed to 193 or 248 nm excimer laser radiation. The fluence was gradually
      increased from 21 to 400 mJ/cm2 in 193 nm (constant total energy of 250 J) and
      from 150 to 377 mJ/cm2 in 248 nm radiation (constant total energy of 500 J).
      Chromatid and chromosome aberrations were then analysed microscopically. RESULTS:
      The yields of chromatid breaks and achromatic lesions depend on the fluence per
      pulse. This dependence contains a linear component, indicating a threshold of
      about 70 mJ/cm2 fluence in 193 nm and of about 250 mJ/cm2 fluence in 248 nm laser
      radiation. An increase of the yield of dicentric chromosomes could only be
      observed at the highest fluence tested (377 mJ/cm2) in the 248 nm series. Over
      126 mJ/cm2 in 193 nm radiation no lymphocytes could be cultured and therefore no
      aberrations could be found. CONCLUSIONS: Our findings show that the fluence of
      193 nm and of 248 nm excimer laser radiation has an effect on the yields of
      chromatid breaks and achromatic lesions in human lymphocytes under in vitro
      conditions.

PMID- 9197555
TI  - The corneal endothelium 12 months after photorefractive keratectomy in high
      myopia.
AB  - PURPOSE: To determine if photorefractive keratectomy with a 193 nm excimer laser
      could cause human corneal endothelial changes, mainly in high dioptric
      treatments. METHODS: 18 patients underwent a treatment ranging from 7 to 13
      diopters at the corneal apex (mean 10.3 +/- 1.4 SD) with an estimated corneal
      thinning ranging from 62 to 116 microns (mean 90.7 +/- 12 SD). In these patients
      a comparison between the number and shape of the corneal endothelial cells has
      been performed before and 12 months after PRK. RESULTS: The mean cell density was
      2818 +/- 337 mm2, before surgery, and 2894 +/- 301 mm2 after 12 months. The
      polymorphic index was 79.0 +/- 2.3, before surgery, and 81.0 +/- 5.0 after 12
      months with no significant changes (p = 0.16 and P = 0.09, respectively).
      CONCLUSIONS: These results show that photorefractive keratectomy does not cause
      any significant observable damage to the central corneal endothelium up to 12
      months after surgery, even in high myopic treatments.

PMID- 9197556
TI  - A method for separation and staining of flat mounts of human corneal endothelium.
AB  - A technique is described in which sheets of corneal endothelium are removed from
      human donor corneo-scleral discs. Celloidin solution was applied to the
      endothelial surface, allowed to dry, peeled off with the attached endothelial
      cell layer and mounted on a glass slide. Following removal of the celloidin with
      acetone, this endothelial cell flat mount was then stained with H&E and
      monoclonal antibodies to cell adhesion molecules. A pilot study of endothelial
      cell adhesion molecule expression in flat mount preparations of 14 corneas showed
      constitutive neural cell adhesion molecule (NCAM) expression, but a lower degree
      of focal expression of intercellular adhesion molecule (ICAM)-1, vascular cell
      adhesion molecule (VACM)-1, P/E-selectin and HLA-DR.

PMID- 9197557
TI  - Micropunctate fluorescein staining of the human corneal surface: microerosions or
      cystic spaces? A non-contact photomicrographic in vivo study.
AB  - PURPOSE: To study in vivo the phenomenon of micropunctate fluorescein staining of
      the human corneal surface. METHODS: Patients were examined in the slit-lamp and
      photographed by the means of photomicrography. The staining pattern of
      fluorescein was compared with that of superimposed rose bengal staining. RESULTS:
      The staining patterns showed a great correspondence. CONCLUSION: The findings
      indicate that micropunctate fluorescein staining probably reveals disruptions of
      intercellular junctions permitting penetration and accumulation of stained fluid
      beneath diseased cells in situ.

PMID- 9197559
TI  - Tear lactoferrin concentration during postoperative ocular inflammation in
      cataract surgery.
AB  - Tear lactoferrin concentration was measured by ELISA technique and followed in 30
      patients undergoing cataract surgery. On the first day following surgery, there
      was a significant decrease in tear lactoferrin concentration followed by a
      gradual return to the initial values during the postoperative observation period
      of 7 days. There was an inverse linear relationship between tear lactoferrin
      concentration and the tear secretion rate measured by a modified Schirmer I test
      (1 min) suggesting a constant lactoferrin secretion by the tear glands. Since
      lactoferrin has known antibacterial and anti-inflammatory effects, the results
      may contribute to further understanding of the microbial vulnerability or
      resistance of the eye following surgical procedures.

PMID- 9197558
TI  - Tear fluid plasmin activity of dry eye patients with Sjogren's syndrome.
AB  - Thirty-two eyes of 16 patients with verified Sjogren's syndrome were examined for
      clinical signs of dry eye. Tear fluid samples were collected for plasmin assay.
      Ophthalmologic examinations included estimation of conjunctival or corneal
      discharge, filament formation and presence of conjunctival or corneal epithelial
      defects, assessment of tear meniscus height and measurement of tear fluid break
      up time, Schirmer test, and fluorescein and Rose-Bengal staining graded by the
      van Bijsterveld score. Tear fluid plasmin activity (IU/l) was determined by a
      fluorometric assay and tear fluid flow (microl/min) was measured for calculation
      of tear fluid plasmin activity release (microIU/min). All patients had relatively
      dry eyes; the mean Schirmer test value was 5.7 +/- 0.5 mm/5 min. The mean tear
      fluid break-up time was also low, 7.7 +/- 0.5 s. The mean Bijsterveld score value
      was 2.5 +/- 0.5. Because collection of tear fluid by microcapillaries for the
      plasmin assay was difficult due to the low tear fluid flow rate, it was necessary
      to drop 20 microl of balanced salt solution topically on the cornea to aspirate a
      tear fluid sample. Despite this, the mean tear fluid plasmin activity was higher
      than in control individuals (7.75 +/- 1.51 IU/l vs. 0.73, range 0.64-0.80 IU/l).
      On the basis of these findings we conclude that elevated tear fluid proteolytic
      activity may play a role in the pathology of dry eye/ocular surface disease.

PMID- 9197560
TI  - Evaluation of conjunctival morphology in thyroid associated eye disease by use of
      impression cytology.
AB  - Thirty-one patients with the diagnosis of thyroid associated eye disease were
      included in the study. Samples were obtained from upper and temporal bulbar
      conjunctiva of both eyes by cellulose acetate filter paper. Control group
      included 20 healthy individuals. In patients with thyroid associated eye disease,
      grade 2 or 3 squamous metaplasia was observed in 32.26% of the samples obtained
      from upper bulbar conjunctiva, whereas this ratio increased to 82.26% in temporal
      bulbar area. None of the control cases showed changes of grade 2 or more. The
      evaluation of cytological changes with respect to clinical findings revealed that
      the main factor responsible for the cytological findings was inflammatory changes
      of the conjunctiva, whereas interpalpebral distance and proptosis had only a
      partial effect.

PMID- 9197561
TI  - Tumour cell proliferation after failed ruthenium plaque radiotherapy for
      posterior uveal melanoma.
AB  - Enucleation following ruthenium plaque radiotherapy for posterior uveal melanoma
      indicates failure of treatment. This study focused on the histopathological
      findings and remaining tumour cell growth fraction in 42 of 46 patients with
      failed ruthenium plaque treatment (of 266 patients treated) for melanoma of the
      choroid or ciliary body. The cause for enucleation was clinically detected tumour
      regrowth in 27 (64%) patients, treatment-related ocular side effects in 12 (29%)
      cases and the patient's personal preference in three (7%) cases. The median time
      elapsing from plaque radiotherapy to enucleation was not significantly different
      for patients with recurrent tumour growth (23 months) compared to those
      enucleated without clinical signs of regrowth (19 months). While all tumours
      showed some regressive features by histopathological examination, only five
      melanomas were completely necrotic and viable-appearing tumours cells were
      present in all of the remaining 37 (88%) irradiated tumours. Microwave processed
      PC-10 immunostainings increased the sensitivity to detect cycling cells compared
      to the sole use of mitotic cell counts. By the former technique, proliferating
      tumour cells were detected in 17 of 23 (74%) studied melanomas of eyes enucleated
      for tumour regrowth following brachytherapy. Also, the number of cycling melanoma
      cells was similar to that of non-irradiated controls managed solely by
      enucleation. In contrast, the proliferative compartments of irradiated, but non
      recurrent, posterior uveal melanomas were significantly reduced compared to those
      of matched controls. Still, cycling tumour cells were present in four of 13 (31%)
      irradiated melanomas, clinically assumed to be successfully treated.

PMID- 9197562
TI  - Effects of viscoelastics on bovine corneal endothelial cells in vitro.
AB  - PURPOSE: To evaluate the possible toxic effects of sodium hyaluronate and
      hydroxypropyl methylcellulose on corneal endothelium. METHODS: Cultured bovine
      corneal endothelial cells (BCEC) were treated with either original Healon (10
      mg/ml) or Methocel (20 mg/ml) for 1 h, or with various dilutions of these
      substances in culture medium for up to one week. The toxicity of the
      viscoelastics was assessed in terms of lactate dehydrogenase (LDH) release into
      the supernatant and of cell density. RESULTS: Neither Healon nor Methocel in a
      dilution of 2 mg/ml enhanced LDH release after 72 h incubation, when compared
      with the control in a confluent model. In a proliferation model neither diluted
      Healon nor Methocel showed apparent inhibitory or stimulatory effects on the
      growth of BCEC up to the highest concentration we tested. When a BCEC monolayer
      was covered for 1 h with either undiluted Healon or undiluted Methocel, a
      significant, though transient, higher LDH release was induced. CONCLUSION: The
      results indicate that the diluted viscoelastics are safe for long time contact
      with BCEC, but undiluted they may temporarily interfere with the metabolism of
      the cytoplasm membranes of BCEC.

PMID- 9197563
TI  - Evidence for a possible synergism between pituitary adenylate cyclase activating
      polypeptide and calcitonin gene-related peptide in porcine ophthalmic artery.
AB  - The activities of pituitary adenylate cyclase activating polypeptide (PACAP) and
      calcitonin gene-related peptide (CGRP) were investigated in isolated segments of
      porcine ophthalmic artery. In artery segments pre-contracted by prostaglandin
      F2alpha, PACAP induced a concentration dependent relaxation, but was clearly less
      potent than CGRP. When 2 x 10(-10) M CGRP (relaxation 4.3 +/- 0.8%, n = 11) and
      10(-8) M PACAP (relaxation 12.4 +/- 3.8%, n = 10) were added together, the
      subsequent relaxation was substantially increased (33.6 +/- 5.6%, p<0.0005). In
      addition, the rate of relaxation was increased. The results indicate that there
      is synergism between low concentrations of CGRP and PACAP in isolated porcine
      ophthalmic artery.

PMID- 9197564
TI  - Accuracy of IOL calculation in cataract surgery.
AB  - The accuracy of IOL calculation using the SRK II formula was studied in 515
      cataract extractions with posterior chamber IOLs. All excessively myopic patients
      (8 patients) and those where we had predicted an emmetropic postoperative result,
      from a consecutive series of 994 patients, were included. Preoperatively the
      patients were divided into different groups according to their refractive status
      and the mean postoperative refraction was calculated in each group. The mean
      postoperative refraction increased almost linearly with increasing myopic status.
      The emmetropic group achieved a mean postoperative refraction of -0.6 D, whilst
      in the most myopic group mean refraction was -1.8 D. We believe that the SRK II
      formula is inaccurate for myopic eyes, and that new formulas are needed, taking
      into account all those factors that make up the dioptric power of an eye.

PMID- 9197565
TI  - Colour vision through intraocular lens.
AB  - Fifty patients aged from 30 to 69 years (mean 54.7 +/- 11.3 years, SD) with a UV
      protected monofocal polymethylmethacrylate intraocular lens (IOL) were examined
      with the Farnsworth-Munsell 100 hue (FM 100) test and the Color Vision Meter 712
      anomaloscope. The spectral transmission of the same kind of IOLs as was used
      surgically was measured with Lambda 2 UV/VIS Spectrometer. In the FM 100 test,
      there was no significant difference between the results of the IOL eyes and
      normal eyes. However, the IOL eyes showed better error scores than the normal
      eyes in the blue-purple box IV in the FM 100 test. In the anomaloscope testing,
      the Rayleigh (red-green) equation showed no differences between the IOL patients
      and controls. In the Moreland (blue) equation, however, the mid matching point
      was significantly shifted towards more green (meaning better blue colour
      sensitivity) in the IOL eyes than in the control eyes. This is due to the
      spectral transmission of the IOLs which showed 80-90% transmission already
      starting at the wavelength of about 420 nm. In comparison, the transmission of
      the normal human lens reaches those percentages near 500 nm or even further at
      advanced age.

PMID- 9197566
TI  - Determination of the influence of effectivity upon residual astigmatism.
AB  - PURPOSE: A computing scheme is described which allows determination of the
      astigmatic contribution of ocular surface effectivity towards residual
      astigmatism. METHODS: This involves paraxial raytracing through astigmatic
      surfaces at random axes and applies the principle of astigmatic decomposition.
      Calculations are shown for averaged data from 66 normal right eyes. Frequency
      distribution graphs demonstrate individual variations. RESULTS: The averaged
      ratio of corneal thickness:anterior chamber:lens thickness cylinder power
      contributions due to effectivity (1:5:17) did not match the ratio of their
      respective intraocular distances (1:7:7); a disproportionate amount of
      astigmatism arose from lens thickness effectivity. Although previous research has
      revealed that results for individual eyes are prone to accummulative experimental
      errors, frequency distribution graphs indicate that effectivity predominantly
      yelds direct astigmatism (axis 180 degrees +/- 22.5 degrees). CONCLUSIONS: This
      computing scheme offers a means of examining the functional ocular morphology of
      astigmatic eyes.

PMID- 9197567
TI  - Cataract and high-pass resolution perimetry.
AB  - The present study describes the influence of cataract on high-pass resolution
      perimetry results. Twenty-five otherwise healthy patients were examined before
      and after cataract surgery. Their preoperative visual acuities ranged from 0.1 to
      0.8 and their mean resolution thresholds from 3.9 to 12.3 dB. Both elevated mean
      thresholds and local visual fields defects were observed. In patients with low
      grade cataract, i.e. preoperative visual acuity 0.3 to 0.65, the mean improvement
      in perimetric results after operation was approximately 1 dB. In patients with
      higher degrees of lens opacity, visual acuity 0.1 to 0.25, the difference between
      pre- and postoperative perimetry results showed a wide range, 1.4-6.2 dB. In
      conclusion, cataract induced different types of visual field defects. The general
      threshold increase due to low-grade cataract (VA > or = 0.3) could be compensated
      for by subtracting 1 dB from the measured value.

PMID- 9197568
TI  - The influence of drop size of cyclopentolate, phenylephrine and tropicamide on
      pupil dilatation and systemic side effects in infants.
AB  - In this prospective study, microdrops (mean drop volume 5.6 microl) and
      commercially available standard drops (mean drop volume 35.4 microl) of
      cyclopentolate, phenylephrine and tropicamide's clinical efficacy and systemic
      side effects were compared. Sixty-one infants requiring diagnostic pupil
      dilatation were studied for pupillary diameter, systemic blood pressure, heart
      rate and skin flushing changes related to the instillation of mydriatic drops.
      Both microdrops and standard drops of the drugs produced significant increase in
      pupillary diameter compared with the baseline (p<0.01). In cyclopentolate and
      phenylephrine groups, there was no significant pupillary diameter changes between
      microdrops and standard drops (p>0.05). Mean blood pressure increased
      significantly in infants given standard drops. There was no significant change in
      the group that was given microdrops. In our opinion, reduced volume of mydriatics
      can prevent possible side effects.

PMID- 9197569
TI  - An improved method to estimate frequency of false positive answers in
      computerized perimetry.
AB  - Reliability of patient performance in static computerized perimetry is important
      for evaluation of results. False positive answers tend to falsely increase
      measured threshold sensitivity. The frequency of false positive responses is
      traditionally measured by adding extra questions, catch trials, to the test.
      Catch trials are few and limited because of time constraints, leading to inexact
      estimates. We developed an improved method for estimation of false positive
      answers by using information already available in current ordinary computerized
      visual field testing, without increasing test time. We here describe the method
      and evaluate it in a prospectively collected material of 49 glaucoma eyes of 49
      patients. The results show that the new method reduces measurement errors
      considerably and significantly as compared with the traditional catch trials
      method. Test-retest change was only half with the new method as compared to the
      traditional method of catch trials. Furthermore, it can reduce test time by
      eliminating the need to use catch trials to estimate the frequency of false
      positive responses.

PMID- 9197570
TI  - Perimetric probability maps to separate change caused by glaucoma from that
      caused by cataract.
AB  - We describe a new method for analysis of change in glaucomatous visual fields
      with the object to differentiate between changes caused by glaucoma from those
      caused by cataract. New pattern deviation change probability maps were developed
      from a prospectively collected glaucoma material and designed to be sensitive to
      changes in localized field loss, but to be unaffected by media-induced perimetric
      change. We compared the new change probability maps with the commercially
      available total deviation change probability maps in series of Humphrey
      perimetric tests in a glaucoma material of 43 eyes of 35 patients, who had
      undergone cataract surgery. When using the total deviation maps, considerable
      differences were seen between fields obtained before and after cataract surgery.
      Much smaller differences were seen when using the new change probability maps,
      that almost eliminated the common and disturbing effect of increasing cataract.
      This new tool could be of considerable help in differentiation between
      progressive glaucomatous visual field loss and deterioration caused by increasing
      media opacities.

PMID- 9197571
TI  - The effect of heparin-surface-modification on scar-tissue formation around a
      subconjunctival polymethylmethacrylate implant in the rabbit.
AB  - PURPOSE: Excessive scar tissue formation around ocular drainage implants is a
      common cause for implant failure. The purpose of this study was to evaluate the
      effect of heparin-surface-modification of a subconjunctival
      polymethylmethacrylate implant on scar-tissue formation in the rabbit eye.
      METHODS: Plain and heparin-surface-modified polymethylmethacrylate implants were
      implanted subconjunctivally in the eyes of 13 rabbits in two groups consisting of
      8 and 5 animals. In the latter group the implants were in contact with aqueous
      humour through a fistula into the anterior chamber. RESULTS: Both unmodified and
      heparin-surface-modified polymethylmethacrylate implants were well tolerated. In
      histological sections studied by both light microscopy and transmission electron
      microscopy, heparin-surface-modification of polymethylmethacrylate implants
      seemed to diminish the formation of scar tissue around the subconjunctival
      implants. CONCLUSION: Heparin-surface-modification of polymethylmethacrylate
      implants could provide one way to affect the formation of excessive fibrous
      tissue around ocular drainage implants.

PMID- 9197572
TI  - Visual impairment in Swedish children. I. Register and prevalence data.
AB  - Knowledge of the epidemiology of visual impairment in children forms one of the
      cornerstones of pediatric ophthalmology. In contrast to e.g. the other Nordic
      countries, Sweden has had no efficient and continuous registration of visually
      impaired children. An epidemiological study on this subject has now been done,
      collecting data on all children and adolescents registered at the Low Vision
      Clinics throughout Sweden. In this work data on 2373 visually impaired children,
      0-19 years of age and living throughout Sweden are presented. Data collected in
      the study include sex, date of birth, county, ocular diagnosis, systemic
      diagnosis, classification of visual impairment, aetiology and possible additional
      impairments. The prevalence of visual impairment as defined by WHO was
      10.9/10,000 inhabitants in the current age group. A slight male preponderance was
      seen compared to the total population 0-19 years. This was not reduced when only
      non-genetic aetiological factors were taken into consideration. A total of 45% of
      the children had only a moderate visual impairment (WHO category 1), whereas
      approximately 25% were found in WHO categories 3,4 and 5, i.e. fulfilled the
      requirements for blindness. Additional impairments were found in 60% of the
      children. Mental impairment in combination with motor impairment or mental
      impairment exclusively were the most common ones seen.

PMID- 9197573
TI  - Visual impairment in Swedish children. II. Etiological factors.
AB  - The analysis of etiological factors in a group of visually impaired children is
      of considerable importance when trying to find guidelines for possible preventive
      work. In this study we present etiological data on 2373 Swedish children. Data
      have been obtained by reviewing medical records on all known children with visual
      impairment throughout the country. In accordance with similar studies from
      industrialised countries, the group with prenatal etiology was the predominant,
      comprising 64% of the material. Within this group, half the patients had a
      disease of genetic origin. A total of 50% of all patients with prenatal etiology
      had an additional impairment, but in the group with diseases of genetic origin
      this proportion was smaller, only 40%. On the other hand, many children with
      additional impairments were found among those with an unspecified prenatal
      influence. Peri-/neonatal etiologies were found in 20% of the patients. In this
      group as many as 83% had additional impairments. This was even more pronounced
      among children delivered at term. The group with infantile/juvenile etiologies
      was small, 7%, with additional impairments in 66%. In 9% of all patients the
      etiology was classified as unknown. Among these, 80% had additional impairments.
      The visual impairment tended to be more pronounced, the later the disease was
      acquired. A male preponderance was seen in most etiological subgroups and in the
      material as a whole.

PMID- 9197574
TI  - Prevalence of congenital colour blindness among Inuit in East Greenland.
AB  - PURPOSE: To establish whether congenital colour blindness among males is still
      rare in Inuit (Eskimos) as indicated previously in 1893 and 1930, especially in
      East Greenland, as demonstrated by Erik Skeller in 1950. METHODS: The study was
      comprised mainly of school children. 540 Inuit in East Greenland were compared to
      545 controls in East Greenland and Denmark examined by three sets of
      pseudoisochromatic plates (Ishihara 1932, original plate used by Skeller),
      Ishihara (1994), and standard P.P. 2 part Igaku-Shoin (1994). RESULTS: Only 1.0%
      of male Inuit (3/290) are colour blind, a significantly lower incidence than the
      8.7% among Danish males in Denmark (15/173). The prevalence was the same in the
      three control groups, Danes in East Greenland, immigrants and Danes in Denmark.
      Deuteranopia is the most common type. Females showed the same low prevalence in
      all four groups. MAJOR CONCLUSIONS: Colour blindness is still remarkably low
      among Inuit in East Greenland as compared with the present three control groups.

PMID- 9197575
TI  - Practice styles and preferences of Danish cataract surgeons--1996 survey.
AB  - A survey of the practice styles and preferences of the members of the Danish
      Ophthalmological Society with address in Denmark was performed in January 1996.
      Only ophthalmologists performing cataract surgery were asked to return the
      questionnaire. Eighty-five responses were received by the cut-off day,
      representing 24 948 cataract operations per year. The data were compared to a
      similar questionnaire analysing the 1995 practice styles and preferences.

PMID- 9197576
TI  - Rhegmatogenous retinal detachment operation after radial keratotomy.
AB  - Radial keratotomy has recently been introduced for the correction of myopia. This
      procedure does not hinder progression of the pathophysiological changes in the
      myopic eye. We hereby describe a case of rhegmatogenous retinal detachment
      operation after radial keratotomy and present the operative considerations and
      refractive results.

PMID- 9197577
TI  - Angle closure caused by multiple, bilateral iridociliary cysts.
AB  - A case of high, broad, peripheral anterior synechiae caused by multiple,
      bilateral iridociliary cysts is reported. The peripheral anterior synechia in our
      case extended to the corneal endothelium beyond Schwalbe's line, and iris atrophy
      in the region of the cysts was found. Ultrasound biomicroscopic imaging showed
      that multiple, bilateral iridociliary cysts causes elevation of the iris
      structure.

PMID- 9197578
TI  - Autosomal dominant retinitis pigmentosa with a rhodopsin mutation (Arg-135-Trp).
      Disease phenotype in a Swedish family.
AB  - We here present the clinical phenotype in 6 patients from a family with autosomal
      dominant retinitis pigmentosa found to carry a point mutation in the rhodopsin
      gene (arginine-135-tryptophan). The mutation is the second found by mutation
      screening of DNA from 20 Swedish families with dominant retinitis pigmentosa.
      With full-field electroretinography we could document a severe form of retinitis
      pigmentosa in patients belonging to the family, similar to the phenotype
      associated with the previously reported mutation (arginine-135-leucine). Our
      results indicate that different point mutations in the same region of the
      rhodopsin gene, resulting in amino acids with similar properties (both
      hydrophobic), may cause a similar clinical phenotype. Further, point mutations in
      this specific region seem to cause an agressive form of retinitis pigmentosa.

PMID- 9197579
TI  - Certification and occupational health nursing. An historical perspective.
AB  - This article is based on excerpts from the Catherine Dempsey Lecture (American
      Occupational Health Conference, 1997), delivered by A. Brian Verrall, Chairman,
      American Board for Occupational Health Nurses, Inc. (ABOHN) in recognition of the
      25th anniversary of ABOHN. The Catherine Dempsey Lecture honors the first
      president of AAOHN. The article is second in a series of three articles
      addressing credentialing to appear in AAOHN Journal. The first article,
      "Credentialing: Concerns and Issues Affecting Occupational Health Nursing," by
      Olson, Verrall, and Lundvall appeared in the May 1997 issue [45(5):231-238].

PMID- 9197580
TI  - Breastfeeding in the workplace. Building a support program for nursing mothers.

PMID- 9197581
TI  - The lift team method for reducing back injuries. A 10 hospital study.

PMID- 9197582
TI  - Workplace violence. Prevention efforts by the occupational health nurse.

PMID- 9197583
TI  - Spirometry.

PMID- 9197584
TI  - The role of electronic information in occupational health nursing.

PMID- 9197585
TI  - New nursing stereotype depicts nurses as 'thick'.

PMID- 9197586
TI  - Nail in the coffin for community care?

PMID- 9197587
TI  - Management of the diabetic patient: causes of leg ulceration.
AB  - The diabetic patient is at risk of developing numerous complications, including
      foot ulceration. The ulcer may contain a neuropathic and ischaemic element.
      Regular preventive checks can assist in early detection of foot problems. Failing
      eye sight and absence of sensation often result in patients relying on the
      healthcare professional detecting abnormalities on their behalf. The long-term
      effects of foot ulceration in the diabetic patient are immobility, septicaemia
      and amputation. Treatment options exist for the neuropathic and ischaemic foot
      but they vary in complexity. Accurate assessment and early recognition of the
      clinical signs of neuropathy and ischaemic ulceration will ensure early detection
      and optimum treatment interventions for the diabetic patient.

PMID- 9197588
TI  - Enhancing the health professional's role in requesting transplant organs.
AB  - The shortfall in organs for transplant continues in the UK. To address this
      problem, methods of organ procurement are continuously widening with the recent
      development of protocols in elective ventilation and non-heart beating donors.
      Until recently, the nurse's role in the success of organ procurement was largely
      limited to those working in intensive care units involved in cadaveric transplant
      and community-based nurses working with patients on kidney dialysis who may
      become involved with live related transplant. Involvement in organ procurement
      has now extended to nurses working in general wards and accident and emergency
      centres. It is imperative that health professionals are aware of the large
      numbers of patients for whom donors have not been found. They need to be aware of
      the possible reasons which deter relatives from giving consent for potential
      donors and prevent relatives themselves from becoming potential live donors.
      Those who are involved in the organ request process need to be alerted to the
      factors that affect the decision to give consent. It is hoped that these efforts
      will help to reduce the drastic shortage of available organs for transplant in
      the UK.

PMID- 9197589
TI  - Effects of resettlement on people with learning disabilities.
AB  - This article describes a small-scale study of the quality of life for people with
      learning disabilities after moving from a large group home with institutional
      features to community settings. The Life Experiences Checklist was chosen to
      provide objective measures of their quality of life before and after the move,
      and a semi-structured questionnaire was used to gain a more personal view of
      their life satisfaction. The results showed that the overall quality of life for
      the service users improved following resettlement. In particular, the home
      environment, leisure facilities, freedom and opportunities for service users had
      all increased significantly. Participants also reported having more choices and
      were more likely to take part in leisure and household activities. However, the
      range and quality of personal relationships experienced by the service users
      showed slight but not significant changes. These findings are discussed in
      relation to previous research, and the importance of quality evaluation is
      considered.

PMID- 9197591
TI  - Nursing care of the mechanically ventilated patient in ITU: 1.
AB  - The mechanically ventilated patient often represents the ultimate in
      vulnerability and demands the highest standards of nursing care. Not only may the
      patient be unconscious but also the artificial airway is an unnatural invasion of
      the most innate physiological mechanism--breathing, and the nurse must safeguard
      this during all aspects of care. Nursing these patients is immensely satisfying
      and varied. It ranges from caring for the patient's activities of daily living to
      carrying out the highly technical and invasive monitoring and interventions which
      require specialist knowledge and skills. This article, the first in a two-part
      series, covers the types of ventilation, suction therapy, oral and eye care,
      elimination, body position, physiotherapy and the physiological effects of
      mechanical ventilation.

PMID- 9197590
TI  - Gentle teaching as an empowering approach to challenging behaviour.
AB  - This article illustrates how gentle teaching (GT) has helped to liberate a young
      woman with severe learning disabilities and challenging behaviour and how this
      process has empowered her parents. The story of Amanda (told by her mother) is
      sadly not unique and many families are struggling at home with their son or
      daughter, with very little practical guidance and support. The author (JA) met
      Amanda's mother (IS) at a GT course run for parents in 1990, where she was acting
      as one of the facilitators. The author maintained involvement with the family
      after the course ended and regular visits were made to the home to work with
      Amanda and her parents. The visits were recorded in a diary and reflection with
      the parents took place on every visit.

PMID- 9197593
TI  - Medical investigations. 2: ERCP.

PMID- 9197594
TI  - Nurses must manage and control healthcare assistants.

PMID- 9197592
TI  - The Flo-tech range of pressure-reducing cushions.
AB  - Early rehabilitation of bed-bound patients has highlighted the need for pressure
      reducing seating to complement pressure-reducing mattresses. The technology
      within cushion manufacturing has responded with a customized contouring principle
      for cushions. This has previously only been available on an individual patient
      basis. The range of Flo-tech cushions has attempted to provide the general
      patient population with a cushion that will reduce pressure, provide support and
      improve posture. The importance of seating in pressure sore prevention cannot be
      overemphasized. The provision of pressure-reducing cushions can assist in
      providing a total package of pressure reduction for the patient.

PMID- 9197595
TI  - Why do nurses face violent assault in A&E?

PMID- 9197596
TI  - Mental health is at the centre of social change.

PMID- 9197597
TI  - I.v. access options for AIDS patients with cytomegalovirus disease.
AB  - In view of changes over the past 2 years in the intravenous (i.v.) management of
      patients with AIDS and cytomegalovirus (CMV) disease, a small study was carried
      out at the Kobler Clinic, an HIV treatment centre in London, to examine optimal
      i.v. access for CMV induction treatment. Thirty lines were analysed over a period
      of 4 months: 18 were peripherally inserted central catheters (PICCs) and 12 were
      midline catheters. Each line was monitored and evaluated for reason for choice of
      line, insertion data, line survival, patient self-administration, patient comfort
      scores, infection rate, and other difficulties encountered during treatment
      induction. The study results indicated noticeable differences between PICC and
      midline catheter performances, although a change in treatment protocol during the
      study influenced the choice of line used. There were also marked differences from
      other studies, carried out predominantly in non-HIV patients, when infection
      rate, dwell time of lines and thrombus formation were compared. Significant
      changes in practice have been implemented and further clinical studies/research
      identified.

PMID- 9197598
TI  - Patient management following suprapubic catheterization.
AB  - This article considers the issue of suprapubic catheterization and the subsequent
      care of the client. The conditions and situations where suprapubic
      catheterization may be used are outlined. A review of the literature on this
      important subject suggests that there is little research/evidence-based practice
      to support some current-day practices. The review addresses such issues as what
      suprapubic catheterization is and how it is carried out. Key issues such as
      avoidance of infection, the need for dressings and care of the insertion site are
      discussed. In particular, the gynaecological field is explored to highlight
      concern about variations and discrepancies in approaches to care of the patient
      with a suprapubic catheter in situ. Finally, a call is made for practitioners to
      base their care on research findings or evidence-based practice rather than
      tradition, ritual or heresy.

PMID- 9197599
TI  - Managed care strategy for mental health services.
AB  - In the UK, managed care is beginning to be recognized as a cost effective,
      quality-driven system which can be used to structure patient care. This article
      examines the potential use of managed care pathways in mental health services,
      focusing on clients with schizophrenia. The strengths of managed care include the
      effective coordination of healthcare resources, the clear accountable audit of
      mental health practice and the re-engineering of mental health practice to
      improve patient outcomes. Problems in designing representative care pathways and
      encouraging healthcare providers to implement care pathways are some of the
      disadvantages of this system.

PMID- 9197600
TI  - Work stress among community psychiatric nurses.
AB  - This article examines the findings of a research study on the levels and sources
      of stress among 60 community psychiatric nurses (CPNs) from six health
      authorities in the midlands area. This three-way comparative study explores the
      stress levels experienced by CPNs working with primary clients. The hypothesis
      that higher levels of stress is experienced by CPNs working with the severely
      mentally ill is supported. The stress levels experienced did appear to vary with
      the type of clients catered for. Using a questionnaire designed to measure
      individual variables, CPNs working with the severely mentally ill reported higher
      caseloads, less training, lack of respect and understanding of their role by
      others and the need for more supervision and support. Forty per cent of CPNs were
      found to be stressed according to the General Health Questionnaire (GHQ 28).
      While there is debate about where CPNs should focus their interventions and which
      clients should be prioritized, it appears that working with the severely mentally
      ill is less attractive and more stressful to CPNs. The results and suggestions
      for further research are highlighted in this article.

PMID- 9197601
TI  - Clinical electives: the challenges and benefits of student choice.
AB  - Traditionally, students have not had the opportunity to exercise choice over the
      specialty and location of their clinical placements. This is now changing but it
      requires the wholehearted commitment of students, their lecturers and all those
      in the institutions concerned. The innovation has to sit coherently within the
      largely externally prescribed curricula approved by the National Boards, the
      professional arm of conjoint validation processes. The challenges are many, but
      the benefits can be immeasurable. This article describes the experiences of one
      university in managing and planning these initiatives and examines students'
      responses to them. Significant questions are raised about developments for the
      future.

PMID- 9197602
TI  - The role of the midwife in perineal wound care following childbirth.
AB  - Midwives have an important role to play in the care of perineal wounds following
      childbirth. A wide variety of practices are carried out in this area. However,
      some current practices may not be beneficial to the promotion of wound healing.
      Midwives must realize the relevance of their care and potential impact, both
      positive and negative, of advocated treatments in wound healing. The maintenance
      of effective pain relief must be balanced with the need to promote wound healing.
      It is important that midwives recognize the need for research-based practice and
      that an audit is set up nationally to evaluate the efficacy of treatments and
      practice. Research, audit and evaluation of services are the central processes
      involved in providing effective and efficient care, as advocated by the
      Department of Health (1993).

PMID- 9197603
TI  - Medical investigations. 4: Bronchoscopy.

PMID- 9197604
TI  - What opportunities will labour provide for nurses?

PMID- 9197605
TI  - What is a life worth?

PMID- 9197606
TI  - More about AAAs.

PMID- 9197607
TI  - Silver spoons is golden.

PMID- 9197608
TI  - Pneumonia in elders.
AB  - In spite of the availability of potent antibiotics and sophisticated diagnostic
      techniques, pneumonia continues to be a serious problem among elders. Respiratory
      infections occur frequently and often are complex. Management is complicated by
      atypical clinical presentations and altered metabolism of pharmacologic agents.
      Community-acquired pneumonia and nosocomial pneumonia are caused by different
      organisms but can have similar clinical presentations. Current therapeutic
      measures and appropriateness of hospitalization are discussed. Via synthesis and
      application of this material, nurses can maximize positive outcomes by
      identifying symptoms, individualizing care, and implementing effective preventive
      education in the acute care setting, as well as in the community.

PMID- 9197609
TI  - Nursing management of elderly patients with asymptomatic bacteriuria.
AB  - Nursing management of elderly patients with asymptomatic bacteriuria encompasses
      an array of basic and complex nursing observations and interventions to eliminate
      or reduce those risk factors that contribute to persistent bacteriuria and to
      identify warning signs of an impending inflammatory response. Selected risk
      factors, the prevalence of bacteriuria in the elderly population, and nursing
      management of clients with asymptomatic bacteriuria are discussed.

PMID- 9197610
TI  - Assessing dressing ability in dementia.
AB  - Cognitive impairment can profoundly affect the skills required for activities of
      daily living (ADL). Most cognitive screening measures assess cognitive status
      rather than the cognitive functions that underlie ADL tasks. The dressing
      assessment guide (DAG) assesses the cognitive and functional abilities in
      dressing of patients with dementia. The DAG evaluates everyday and overlearned
      tasks and uses cues to provide a context for action. Nurses can easily administer
      the guide, and the resulting data provide the basis for nursing interventions.

PMID- 9197611
TI  - Preventing agitated behaviors during bath time.
AB  - Bathing people with Alzheimer's disease or other dementia is frequently
      associated with agitated and resistive behaviors. Bathing involves multiple
      competing stressors, and persons with dementia have a decreased threshold for
      tolerating stress from the environment. This article provides practical
      suggestions for decreasing environmental stressors and agitation during the
      bathing activity. Communicating respect and supporting the dignity of the person
      are emphasized.

PMID- 9197612
TI  - Identification and assistance for chemically dependent nurses working in long
      term care.
AB  - The purpose of this manuscript is to examine impaired nurses' practice, to
      identify causes, signs, and symptoms of problems, and to identify interventions
      for chemically dependent nurses employed in long-term care. The long-term care
      nurse manager has a moral, ethical, and legal responsibility to assist the
      chemically dependent nurse and to protect the resident and the facility.
      Education of nurse managers is essential to provide for intervention and
      treatment for the chemically dependent nurse. Assisting the nurse to accept
      treatment and return to practice benefits the individuals, the facility, and the
      profession. This manuscript describes step-by-step interventions for
      identification, treatment, and return to work for chemically dependent nurses.

PMID- 9197613
TI  - Review and analysis of caregiver burden and nursing home placement.
AB  - Research studies published between 1989 and 1995 were analyzed to identify
      variables that led to caregiver burden and nursing home placement of nondemented
      elders. Although the variables impact each caregiving situation differently,
      decreased functional abilities of the care receiver, interrupted sleep of the
      caregiver, or the presence of multiple factors within the caregiving situation
      were positively correlated with caregiver burden and increased risk of nursing
      home placement. Increased awareness of these issues is essential to provide
      successfully for the aging population. Health care professionals should assess
      for these factors and plan interventions. Further research is needed to better
      meet the needs of the elderly caregiver and care receiver.

PMID- 9197614
TI  - Bernita Steffl: a geriatric nurse with a talent for listening, learning, and
      leading. Interview by Priscilla Ebersole.

PMID- 9197615
TI  - New hope for stroke victims.

PMID- 9197616
TI  - Weight loss resulting from Alzheimer's disease.

PMID- 9197618
TI  - Wellness for people 65 years and better.
AB  - Wellness is within the grasp of all persons, no matter what age. Gerontological
      nurses, in care partnerships with other disciplines and business and health
      organizations, still have numerous opportunities in their communities to
      contribute to the well-being of aged individuals. Only 68% of the sentinel
      objectives established by The Public Health Service in Healthy People 2000 have
      shown improvement (Peterson, 1996). There is still room for development of the
      Healthy People 2000 initiatives and various opportunities for gerontological
      nurses to assist elders on their journey to wellness.

PMID- 9197617
TI  - Managing mental illness at home.

PMID- 9197619
TI  - The Hispanic elderly: implications for nursing care.
AB  - The elderly Hispanic population is growing and with them will also grow their
      demand for nursing care. The purpose of this article was to establish some
      general guidelines that might help the nurse have a better understanding of who
      the Hispanic elder client is. As alluded to earlier, if there is one word to
      describe the Hispanic elder client it would be "diverse." As such, the reader is
      reminded that the discussion of the factors and interventions in care outlined
      here will not apply to all Hispanic clients all of the time. The Hispanic elder
      client will act differently depending on their Hispanic subgroup heritage and on
      their special personal history. In fact, most of the literature is based on
      research with Mexican-Americans who comprise the largest group of Hispanics in
      the United States. As such, there may be some bias in an attempt to generalize
      the findings discussed here across all Hispanics. The nurse is encouraged to
      acknowledge the specific sociocultural background of each individual and to plan
      and execute sensitive, tactful interventions that help to maximize the
      individual's health while valuing their uniqueness. Finally, being in touch with
      one's own values and beliefs will help to ensure that holistic nursing be
      implemented as a tool that is both comprehensive and sensitive to the various
      factors surrounding the Hispanic elder.

PMID- 9197620
TI  - Chronic pain management of older adults in residential settings.

PMID- 9197621
TI  - Hypodermoclysis therapy. In a chronic care hospital setting.
AB  - Occasionally, elderly patients experience acute, episodic incidents of illness
      that result in dehydration or a high potential for dehydration (e.g., flu,
      diarrhea). At times, patients may be unable, or refuse, to take fluids orally.
      Enteral routes via a nasogastric tube or enteral stomach tube may also not be
      available. In the past, these patients often had to be transferred from home or
      long-term care facilities to an acute care hospital for intravenous therapy. A
      transfer of the acutely ill elderly patient to an acute care hospital is often
      very stressful to the patient and his/her family and is costly to the health care
      delivery system. Hypodermoclysis, the process of rehydrating a patient by
      providing isotonic fluids into the subcutaneous tissues over a short time period,
      provides an alternative method to deal with acute, short-term fluid deficit
      problems in the elderly. Hypodermoclysis therapy can be administered in a chronic
      care setting thus potentially decreasing the need to transfer the elderly client
      to an acute care hospital. The purpose of this study was to investigate the use
      of hypodermoclysis therapy in solving acute, or potentially acute fluid deficit
      problems, that were anticipated to be both reversible and short term in nature.
      This was carried out in an elderly population that resided in a 284-bed chronic
      care hospital in southern Ontario.

PMID- 9197622
TI  - Expanding the scope of continuity theory. Application to gerontological nursing.
AB  - Continuity Theory is a psychosocial theory of aging which posits that as middle
      aged and elderly adults adapt to changes associated with the normal aging
      process, their past experiences, decisions, and behaviors will form the
      foundation for their present and future decisions and behaviors. Regardless of
      the clinical setting, nurses working with elderly individuals may find Continuity
      Theory helpful in viewing the experience of elders in a holistic way that
      incorporates a life course perspective. By applying Continuity Theory to clinical
      practice, nurses may be better able to provide individualized, clinically
      appropriate care to elders.

PMID- 9197623
TI  - Breaking the silence: a health promotion approach to osteoporosis.

PMID- 9197624
TI  - The "Think Aloud" seminar for teaching clinical reasoning: a case study of a
      child with pharyngitis.
AB  - The "Think Aloud" seminar is a group teaching method to assist pediatric nurse
      practitioner students to develop critical thinking and clinical reasoning skills.
      Seminar proceedings simulate the iterative clinical reasoning process that occurs
      in an actual clinic or office visit. Students' requests for subjective and
      objective data must be followed by the rationale as to why the information was
      requested. This method is effective for teaching and evaluating students' skills
      in differential diagnosis and management of common illness in children. The
      process will be demonstrated with the presenting symptom of a sore throat
      followed by a description of the procedures that are used. J Pediatr Health Care.

PMID- 9197625
TI  - Preschool injuries in child care centers: nursing strategies for prevention.
AB  - Injuries to children 0 to 12 years of age pose a national health problem.
      Injuries are a particular problem in child care settings. Both research and
      anecdotal reports confirm that most injuries in the child care setting are cuts,
      scratches, and abrasions caused by falls indoors and in playgrounds. Other
      injuries are caused by human bites and motor vehicle pedestrian injuries. Child
      development centers are an obvious focal point to direct injury prevention
      services by nurses. The nurse's role in injury prevention is to educate the child
      care providers about injuries and then teach them the skills to assess and
      monitor injury prevention strategies. This article discusses the problem of
      injuries in child care centers in general and discusses injury prevention
      strategies the nurse can share with the child care provider. Educational
      resources are included to help the child care providers assess and monitor their
      own center's injury risk. J Pediatr Health Care.

PMID- 9197626
TI  - Health care of the internationally adopted child. Part 2: Chronic care long-term
      medical issues.
AB  - Internationally adopted children remain at risk throughout their lives for
      medical sequelae related to their birth and residence in a foreign country. In
      the early period after placement the most important problems are the management
      of chronic infectious diseases and malnutrition. Over time, however, many
      children will have issues related to growth, age determination, timing of
      puberty, dental care, development, and language acquisition. Chronic disease and
      ethnic health considerations pose some special problems for the adopted child
      without a personal or family history. Part 1 of this series addressed the initial
      evaluation for the newly arrived internationally adopted child, whereas part 2
      discusses the long-term management problems. J Pediatr Health Care.

PMID- 9197627
TI  - Caring for children in foster care.

PMID- 9197628
TI  - Attention deficit/hyperactivity disorder.

PMID- 9197629
TI  - Failure to thrive: a clinical guideline. University of Texas. Houston Health
      Science Center.

PMID- 9197630
TI  - Torticollis in infancy.

PMID- 9197631
TI  - Coverage and reimbursement issues for nurse practitioners.

PMID- 9197632
TI  - Contraceptive options for adolescents.

PMID- 9197633
TI  - Newborn discharge and follow-up care, National Association of Pediatric Nurse
      Associates and Practitioners.

PMID- 9197634
TI  - What nurse has been used as she or he has been prepared?

PMID- 9197635
TI  - Interdisciplinarity: the story of a journey.
AB  - Everywhere we turn, interdisciplinarity has become a key concept guiding health
      care education and practice. Granting agencies call for it. Educational and
      health policy makers extol its virtues. Accreditation agencies across health
      disciplines recommend it as a competency for the present and future. But what is
      it? How do we get it from our educational and practice systems that are
      compartmentalized by claims to discipline-specific knowledge, tradition, and the
      flow of dollars from funding sources? What is it like after we do get it? And
      most of all, why would we ever want it in the first place? We have had some
      significant experience within our Division of Health Sciences in
      interdisciplinary teaching, practice, and scholarship. Our experience was
      initially framed by implementation of one of the seven W.K. Kellogg Foundation
      Community Partnerships for Health Professions Education grants. The grant brought
      the education of medical, nursing, and other health professions students out of
      the hospital to interdisciplinary primary care experiences in and with the
      community. We will never tell you we have a straightforward prescription for
      success. Living interdisciplinarity, like living life itself, is something that
      frequently poses more questions than it answers. We will, with enthusiasm, share
      with you what we have learned in our unique journey together in hopes that you
      and your colleagues will find something useful for your own voyage into
      interdisciplinarity.

PMID- 9197636
TI  - Whence the 11 percent rule?

PMID- 9197637
TI  - Art of the paradigm shift.
AB  - How long has it been since you've had a good paradigm shift? No, it's nothing you
      can plan. Nothing you can simply tick off that perennial list of To Do's tucked
      away in your pocket or some unoccupied sulcus of your brain. Paradigm shifts
      simply happen when you are on a journey of discovery. Once they happen, they
      change forever the way you look at the world.

PMID- 9197638
TI  - Nursing education to celebrate learning.
AB  - Institutions of higher education currently face a number of challenges, from the
      increasing diversity of students, a growing disparity between what society and
      what the university defines as its core mission, and society's transition from an
      industrial economy to an information economy. As part of such institutions,
      schools of nursing will need to consider a new "business design," which may
      include: new course formats that will keep groups of students together for
      several years in the same "learning communities"; use of Internet communications
      for projects and public exhibitions and defenses of results instead of the
      regular weekly scheduled class; offering programs for learning entrepreneurship,
      business practice, management, and leadership; and establishing programs for
      working professionals that promise, deliver, and certify specified competencies.

PMID- 9197639
TI  - 50th anniversary of the Division of Nursing. U.S. Public Health Service.
AB  - The National League for Nursing is pleased to join in celebrating the 50th
      Anniversary of the Division of Nursing, U.S. Public Health Service (USPHS). The
      nursing profession and the populations served by the profession have been the
      beneficiaries of the accomplishments of the Division of Nursing and of the
      leadership provided by the directors of the Division. Many of the advances in
      education, practice, and research can indeed be attributed to the support for
      nursing provided through the important activities carried out by the Division of
      Nursing.

PMID- 9197640
TI  - A faculty on the move into the community.
AB  - Faculty at the University of Rochester School of Nursing initiated a curricular
      redesign to prepare students for the evolving demands of the health care job
      market and the changing nature of the nursing profession. The concept of the
      "Learning Community" serves as the metaphor for the new vision of clinical
      education: a set of collaborative and dynamic relationships of students, faculty,
      clinicians, health care consumers and institutional and community sites with the
      mutual responsibility for the education of students and the health of all
      partners. Students experience firsthand the new capabilities required of
      professionals in the new context of health care as more than illness care.

PMID- 9197641
TI  - Baccalaureate and Master's Degree Programs in Nursing. Accredited by the NLNAC
      1997-98.

PMID- 9197642
TI  - The history of NLN.

PMID- 9197645
TI  - Refining a physical assessment course.

PMID- 9197644
TI  - Developing a complete evaluation instrument package.

PMID- 9197643
TI  - Is cloning moral?

PMID- 9197646
TI  - A step-by-step guide to curriculum revisions.

PMID- 9197647
TI  - Dolls and balloons: creating a fetal facsimile.
AB  - A baby doll in a water-filled balloon creates an impressive fetal facsimile. This
      effective visual and tactile adjunct to lectures is simple to construct and
      inexpensive. The fetal facsimile helps engage the attention of students,
      stimulates discussion, encourages questions, and provides a means for skill
      development. Directions for constructing a fetal facsimile and tips for classroom
      use are provided.

PMID- 9197648
TI  - The genogram: a health assessment tool.

PMID- 9197649
TI  - Creating a caring community in nursing education.
AB  - In response to the call to reclaim caring in nursing, an associate of science in
      nursing degree program recently incorporated a curriculum that emphasizes the
      teaching and learning of caring. To accomplish this goal, caring groups composed
      of nursing faculty and students were established. The caring group experience
      involved the creation of a safe place in which nursing students and faculty could
      engage each other in a reciprocal dialogue of sharing and support. This article
      reports the findings of a qualitative study designed to discover and describe the
      lived experience of being in a caring group from the perspective of nursing
      students. Participants reported being more aware of the meaning and importance of
      caring in their personal and professional lives, being more accepting of others,
      and valuing caring and self-care more. They also expressed an intention to
      recreate the caring group experience in future practice settings. Conclusions
      from this study address the pedagogical measures necessary to sustain care and
      caring as the essence of nursing.

PMID- 9197650
TI  - Critical thinking strategies in the classroom: those that did and did not work.

PMID- 9197651
TI  - Career planning. The nurse educator as facilitator and career counselor.
AB  - In a rapidly changing healthcare environment, nurses approaching career planning
      need a stable core of principles and a flexible set of guidelines from which to
      consider existing and emerging opportunities. A five-stage, decision-making
      career plan is discussed.

PMID- 9197653
TI  - A change from the annotated bibliography: a reading analysis project.

PMID- 9197652
TI  - Promoting active learning in large lecture classes.
AB  - Changes in healthcare systems challenge nurse educators to prepare students for
      roles as effective care managers in collaborative practice models in hospital and
      community settings. Instructional strategies that foster student initiative,
      clinical decision-making skills, and competence with interpersonal communications
      are presented for a large undergraduate class to be taught by one faculty member.

PMID- 9197654
TI  - Teaching cultural competence. The value of experiential learning and community
      resources.
AB  - Nurse educators are responsible for developing graduates who are culturally
      competent care givers and marketable as culturally sensitive coworkers. An
      undergraduate course in transcultural nursing is described that relies heavily on
      experiential learning activities and local community resources. Student
      evaluations reveal both immediate and long-term effects of this course on
      graduates' clinical practice.

PMID- 9197655
TI  - Strategic planning in academic nursing.
AB  - Dramatic transformations are occurring in higher education. As colleges of
      nursing compete with other university colleges for limited resources, new
      strategies are needed to be successful. One university's unique strategic
      planning process is presented.

PMID- 9197657
TI  - Teaching research utilization in a baccalaureate nursing program.

PMID- 9197656
TI  - Teaching critical thinking skills to undergraduate nursing students.
AB  - Teaching nursing students to use critical thinking skills is important in today's
      changing healthcare system. Formal instruction in critical thinking theory is
      included in a professional issues nursing course for junior nursing students. The
      authors describe healthcare and non-healthcare educational activities used to
      promote application of the principles of critical thinking.

PMID- 9197658
TI  - The reflective clinician.
AB  - As students struggle to determine what is important in their lives and to
      incorporate nursing into their existence, they are encouraged to share their
      thoughts and explore new insights in a nursing/humanities course, The Reflective
      Clinician. The authors describe the rationale for placing humanities in a nursing
      curriculum and describe strategies and content to be included in the course.
      Student narratives of their perceptions of the course are offered for
      illustration and to give examples of growth experienced by the participants.

PMID- 9197659
TI  - Superhighway for the future of nursing: signposts.

PMID- 9197660
TI  - Transforming impostors into heroes. Metaphors for innovative nursing education.
AB  - Nurses negotiating professional transitions, whether they are entering an
      academic program or assuming a new role in the workplace, often feel like
      impostors. The metaphor of the hero can serve as an "antidote" to the impostor
      syndrome. The author describes an educational experience shaped around the
      impostor and hero metaphors that integrates feminist process with expressive
      methods to transform nurses' perceptions of themselves from impostors into
      heroes.

PMID- 9197661
TI  - Learner-centered group practice as a teaching model.

PMID- 9197662
TI  - How many cases can a case manager manage?

PMID- 9197663
TI  - Clinical pathways in the perioperative setting.
AB  - Clinical pathways have been implemented in a variety of health-care settings.
      They serve as a useful tool for case managers in acute care settings as well as
      ambulatory care settings, skilled care facilities, and long-term care facilities.
      The use of these tools in the perioperative setting, along with variance
      documentation and data feedback is presented here. By creating tangible
      definitions of quality in the perioperative setting, clinical pathways improve
      patient care and assure clinical consistency and continuity of care.

PMID- 9197664
TI  - The art of negotiation.

PMID- 9197665
TI  - Quality problem solving, decision making, type theory, and case managers, Part
      II.
AB  - Temperament style is one way for case managers and those with whom they interact
      to examine theirs strengths and liabilities and to improve individual and group
      problem solving, decision making, and team effectiveness. Part I examined
      components of decision making, personality theory, and described the major
      cognitive types. This article will provide the results of a study of case
      manager's types and discuss the implications of typewatching to delegation, team
      building/groups, negotiation, and problem solving.

PMID- 9197666
TI  - Fast track transurethral resection of the prostate: application of case map
      improves length of stay without compromising patient outcome.

PMID- 9197667
TI  - Implementation of collaborative practice through interdisciplinary rounds on a
      general surgery service.
AB  - Interdisciplinary teaching rounds were initiated on a general surgery service at
      a university teaching hospital. These rounds were designed to promote more
      efficient patient care by providing an opportunity for enhanced communication
      among health-care professionals. Improved collaboration is a prerequisite for
      implementation of critical paths and case management. The authors describe their
      methods of rounds development and the impact of the rounds on patient outcomes.

PMID- 9197668
TI  - Nurse and physician perspectives on clinical pathways.

PMID- 9197669
TI  - The road less traveled.

PMID- 9197670
TI  - The evolution of case management. One organization's experience.
AB  - The case management program at Stanford Health Services has evolved over the past
      5 years in response to the changing managed care marketplace and institutional
      needs. The challenge for the program has been to meet rapidly changing needs of
      both internal and external customers: patients, physicians, staff, and payers.
      The program has evolved from an inpatient model integrating discharge planning
      and utilization review, to include ambulatory case management in the clinic
      setting, management of prepaid health enrollees in the community, and clinical
      pathways. This article will describe the evolution of case management at Stanford
      and individual program components that resulted in significant savings to the
      organization.

PMID- 9197671
TI  - Computers in case management. Advancing health care delivery through technology.
AB  - Fast efficient access to patient information is an essential management tool in
      the current healthcare environment. The clinical case management computer module
      at Stanford Health Services provides and integrates essential patient data
      elements to facilitate clinical case coordination and assist the nurse case
      managers with documentation of clinical data for discharge planning and
      utilization review. Information systems such as this one are critical to the
      provision of comprehensive, cost-effective patient care management.

PMID- 9197672
TI  - Computer spreadsheets: an effective way to manage, analyze, and present quality
      indicators.

PMID- 9197673
TI  - Pain management documenting the decision making process.
AB  - From patient admission to discharge, pain is a critical symptom of concern to the
      nurse case manager. This descriptive study examined nurses' decision-making
      regarding pain management as documented in clinical records of patients after
      orthopedic surgery. Using a Nurses' Pain Management Audit Tool, data analysis
      revealed that during the first 24 hours after emergence from the Post-Anesthesia
      Care Unit, these patients received less than 50% of the narcotic doses available
      for their pain relief. Nurses documented less than 25% of the "ideal occurrences"
      possible for pain assessment, as described in the Agency for Health Care Policy
      and Research Guidelines. Incomplete databases for guiding patient outcomes of
      effective pain management were perpetuated by insufficient documentation. Nurse
      case managers could stimulate increased commitment and quality improvement in
      pain management as a crucial aspect of patient care.

PMID- 9197674
TI  - The next frontier in clinical pathways. The journey to outcomes management.
AB  - The Children's Memorial Hospital, a 265-bed pediatric hospital in Chicago,
      Illinois, is a leader in pediatric clinical pathway development. Significant
      improvements in care coordination and cost savings have been realized from the 14
      pathways implemented to date. Use of a project management methodology and
      adaptation of continuous quality improvement tools for pathway development have
      proven effective to streamline and standardize this process. Despite its success
      in pathway development, Children's Memorial Hospital has realized the need to go
      further. It is necessary to measure outcomes--real clinical, patient outcomes-
      not just financial or utilization outcomes. Solid comparative data from which
      practice changes can be made are needed. Additional ways must be found to
      facilitate movement along the care continuum. Pathways must be used consistently.
      This article will outline the process Children's Memorial Hospital used and share
      the development tools that have been implemented. Children's Memorial Hospital's
      vision for the future and the technology designed to realize that vision are
      delineated.

PMID- 9197675
TI  - Strategies for decreasing documentation: an example in maternal child health.

PMID- 9197676
TI  - How the case manager can influence the clinical information system selection
      process.
AB  - The selection and implementation of a clinical information system that provides
      meaningful patient data in a format that is usable by the clinician is a
      challenge facing many healthcare institutions. In the first issue of Nursing Case
      Management, we explored the information needs of the nurse case manager and the
      available and emerging computerized information systems tools to meet these
      specific needs. This follow-up article will focus on a typical clinical
      information system selection process; outline specific ways the nurse case
      manager can effectively influence that process; and provide examples and a
      checklist that will enable the nurse case manager to assist the institution in
      selecting and implementing the most appropriate system.

PMID- 9197677
TI  - Blood from a turnip. Financial models in case management.
AB  - The Baptist Health System has saved more than $5.4 million in a 3-year period as
      a result of its comprehensive case management program. The key to its success has
      been the pairing of financial cost data with key clinical information. Sharing
      this information with physicians and employing clinical experts as case managers
      has dramatically affected patient care across the continuum at the Baptist Health
      System. With more than 8 years of case management experience, the Baptist Health
      System's financial model has evolved into a concise method of measuring cost at
      the patient/day level. This cost information is analyzed by team members and used
      to improve patient care. At the core of this process is the case manager. By
      providing the case manager with the resources necessary, any healthcare
      institution can achieve significant financial savings and clinical process
      improvement.

PMID- 9197678
TI  - Inpatient meets ambulatory care case management: good for hospitals.

PMID- 9197679
TI  - The silent stakeholder.

PMID- 9197680
TI  - Preparing to automate the case management process.
AB  - In this article, the authors discuss case management automation and the
      preparation that an organization should be making to install such a system
      successfully. They begin with a discussion of the goals of case management
      automation, and then review the steps that all facilities with case management
      programs can undertake to standardize their process, structure their
      organization, and strategically plan for case management automation. The current
      status of case management automation efforts also is discussed. The authors
      conclude by describing the efforts of one organization to develop an integrated
      case management documentation system.

PMID- 9197681
TI  - Outcomes assessment/analysis report: a tool to measure case management services.

PMID- 9197682
TI  - A ten-step process to develop case management plans.
AB  - The use of case management plans has contained cost and improved quality of care
      successfully. However, the process of developing these plans remains a great
      challenge for healthcare executives. In this article, the author presents the
      answer to this challenge by discussing a 10-step format process that
      administrators of patient care services and case managers can adapt to their
      institutions. It also can be used by interdisciplinary team members as a
      practical guide to develop a specific case management plan. This process is
      applicable to any care setting (acute, ambulatory, long term, and home care),
      diagnosis, or procedure. It is particularly important for those organizations
      that currently do not have a deliberate and systematic process to develop case
      management plans and are struggling with how to improve the efficiency and
      productivity of interdisciplinary teams charged with developing case management
      plans.

PMID- 9197683
TI  - Patient pathways for extracorporeal shock wave lithotripsy.

PMID- 9197684
TI  - Job stress versus success factors for case management.
AB  - Job stress is all too common in the case management profession. Recognizing the
      signs and symptoms of stress and understanding its causes will help the nurse
      case manager minimize the deleterious effects of "burnout." The following article
      is an excerpt from the book. Nursing Case Management: A Practical Guide to
      Success in Managed Care. The author explores eight techniques to reduce stress
      and improve performance. The information can be used by the individual case
      manager or by supervisors and coworkers trying to help fellow case managers.

PMID- 9197685
TI  - Future healthcare: the expanding role of the occupational health nurse case
      manager.

PMID- 9197686
TI  - Case management plans and their application to maternal-child health.
AB  - The implementation of case management plans in the maternal-child health
      environment is quickly escalating as the managed care industry infiltrates the
      country. Most institutions began their initiatives in the medical-surgical arena,
      where length of stay and cost reduction opportunities pose the greatest
      challenges but also the greatest opportunities. However, recent case management
      focus in pediatrics and neonatal intensive care units have demonstrated
      successful results.

PMID- 9197687
TI  - The new government's agenda.

PMID- 9197688
TI  - South Africa celebrates democratic nursing.

PMID- 9197690
TI  - Effective change.

PMID- 9197689
TI  - Visionary countdown.

PMID- 9197691
TI  - The long goodbye.

PMID- 9197692
TI  - Reform and re-form.

PMID- 9197693
TI  - Towards evidence based practice.

PMID- 9197694
TI  - The leadership challenge in nursing.

PMID- 9197695
TI  - Management by results.

PMID- 9197696
TI  - Leadership and team building.

PMID- 9197697
TI  - The pace of change in health care delivery is faster here than elsewhere.

PMID- 9197698
TI  - Making sense of the new Government white papers.

PMID- 9197699
TI  - Abuse and bullying.

PMID- 9197700
TI  - Slaves to the system.

PMID- 9197701
TI  - Coaching for change. Realising the potential for nursing.

PMID- 9197702
TI  - The leadership challenge in nursing.

PMID- 9197703
TI  - From whiner to winner.

PMID- 9197704
TI  - Evidence based nursing.

PMID- 9197705
TI  - The nursing home market.

PMID- 9197706
TI  - The longest awaited and most predictable election of the century.

PMID- 9197707
TI  - The EC Working Time Directive.

PMID- 9197708
TI  - The power to lead.

PMID- 9197709
TI  - Lessons learned from geese.

PMID- 9197710
TI  - Leadership in learning disability nursing.

PMID- 9197711
TI  - Christine Hancock. Interview by Tom Keighley.

PMID- 9197712
TI  - New nursing structures.

PMID- 9197713
TI  - Abuse and bullying.

PMID- 9197714
TI  - Generic management.

PMID- 9197715
TI  - Concept inventing: unitary creations.

PMID- 9197716
TI  - The many faces of change: discomfort with the new.

PMID- 9197717
TI  - Qualitative research with children as participants.

PMID- 9197718
TI  - Reengineered healthcare: why nurses matter.

PMID- 9197719
TI  - Reflections on Mitchell's reflection.

PMID- 9197720
TI  - Nursing: the ontology of the discipline.
AB  - The purpose of this article is to contribute to clarifying the ontology of the
      discipline by extending existing meanings of the term nursing to propose a
      substantive definition. In this definition, nursing is viewed as an inherent
      human process of well-being, manifested by complexity and integration in human
      systems. The nature of this process and theoretical implications of the new
      nursing are presented. Nurses are invited to continue the dialogue about the
      meaning of the term and explore the implications of nursing, substantively
      defined, for their practice and science.

PMID- 9197721
TI  - Joy-sorrow: a study using the Parse research method.
AB  - The purpose of this research was to uncover a structure of the lived experience
      of joy-sorrow using the Parse research method. Eleven women over 65 years of age
      volunteered to participate in the study by engaging in audio- and videotaped
      dialogues with the researcher about the phenomenon. The structure of the lived
      experience of joy-sorrow was found to be pleasure amid adversity emerging in the
      cherished contentment of benevolent engagements. Recommendations for further
      research and practice are specified.

PMID- 9197723
TI  - A case for theory triangulation.
AB  - Although theory triangulation has not received much attention in the nursing
      literature, its deliberate, strategic use can be an invaluable guide to reviewing
      literature and designing research. It can enlarge the framing of questions for
      orderly data collection and analysis, and can lay out a route for rational,
      coherent study-clustering. An example is presented that triangulates two nursing
      theories to address a frequently studied problem--nurses' attitudes about AIDS
      care. The absence of firm theoretical footing in exploring this problem has
      limited the application of a large, continuously growing body of empirical data.
      Triangulation is suggested to organize these data, to clarify apparently
      inconsistent findings, and to guide research. The example demonstrates how the
      exploration of related questions not addressed by a single theory may be aided by
      searching for linkages among mid-range theories, including theories from other
      disciplines.

PMID- 9197722
TI  - Human patterning and chronic pain.
AB  - The purpose of this study was to explore the nature of chronic pain through
      Rogerian nursing science. A matched sample was drawn from persons within chronic
      pain management programs (N = 113) and community dwelling adults without chronic
      pain (N = 113). The Human Field Motion Tool and the Power as Knowing
      Participation in Change Tool were used as measures of pattern manifestation
      (alphas = .94). Multivariate analysis of variance revealed significant
      differences between groups on patterning measures (p < .001). Although
      sociodemographic and pain variables were included in the analysis, they were not
      found to be related to patterning differences. The results of this study provide
      support for conceptualizing chronic pain as a pattern manifestation. Determining
      implications of this finding are among recommendations for knowledge development
      in explicating a nursing science perspective on pain.

PMID- 9197724
TI  - A sense of loss: working with loss and people who have a learning disability.
AB  - For many years people with learning disabilities have had forgotten bereavements,
      forgotten grief and have often become forgotten people when it comes to
      meaningful support over the death of a loved one. This Learning Unit aims to
      explore some of the issues involved in the sensitive area of bereavement, loss
      and learning disabilities and to examine critically the role of the learning
      disability nurse in supporting this client group.

PMID- 9197725
TI  - Inappropriate relationships between nurses and patients.

PMID- 9197726
TI  - Payback time for Dobson.

PMID- 9197727
TI  - No time to drop the guard.

PMID- 9197728
TI  - Relative merits.

PMID- 9197729
TI  - Where injustice is seen to be done.

PMID- 9197730
TI  - Tomorrow's people.

PMID- 9197731
TI  - Careering off the path.

PMID- 9197732
TI  - Relationships with patients.

PMID- 9197733
TI  - Understanding schizophrenia.

PMID- 9197734
TI  - Mood swing.

PMID- 9197735
TI  - Guidance for nurses working with children.
AB  - This report sets out the RCN's guidance in response to recent cases where
      children have been harmed by nurses and other healthcare staff. Nurses are
      vulnerable to such allegations and must therefore develop strategies which
      protect both the child and the professional from false accusations.

PMID- 9197736
TI  - The ward sister/charge nurse as 'on site' manager.
AB  - The traditional role of ward sister/charge nurse has been redefined as ward
      manager with the devolving of many new responsibilities, including acting as 'on
      site' manager out of hours. Using a self-report questionnaire, the study explored
      the experiences of all ward managers performing hospital cover within one
      hospital (n = 18). Common problems encountered included arranging cover for staff
      absence at short notice and bed management. The sample group viewed the addition
      of hospital cover as an appropriate development in the role of ward manager.
      However, few gained any job satisfaction from the role, citing growing time
      commitment, increasing absence from clinical areas and feelings of stress as
      possible causes. In addition, the study highlighted the lack of preparation ward
      managers had received before involvement with hospital cover.

PMID- 9197737
TI  - Prompt treatment for chemical eye injuries.
AB  - A chemical injury to the eye requires prompt and effective treatment to minimise
      permanent damage. This article describes the types of chemical injury and
      discusses the treatments available.

PMID- 9197738
TI  - Establishing a public health nursing project.
AB  - This article, the second in our three-part series on public health, describes the
      development and operation of two public health projects in Stockport. The authors
      place these projects in the wider context of public health nursing and highlight
      some of the benefits of using the approach as a framework for community project
      work.

PMID- 9197739
TI  - Developing nursing roles.

PMID- 9197741
TI  - Violence in A&E departments.

PMID- 9197740
TI  - Clinical macronutrition.

PMID- 9197742
TI  - Changing the guard.

PMID- 9197743
TI  - Emergency witnesses.

PMID- 9197744
TI  - Nursing must fight to reclaim a valuable role in continuing care.

PMID- 9197745
TI  - Root treatment.

PMID- 9197747
TI  - Mother knows best?

PMID- 9197746
TI  - The bane of Albania.

PMID- 9197748
TI  - Platform for principles.

PMID- 9197749
TI  - A bit of a do.

PMID- 9197750
TI  - New Labour new NHS.

PMID- 9197752
TI  - Bottling out.

PMID- 9197751
TI  - The baby killer.

PMID- 9197753
TI  - New air of confidence.

PMID- 9197754
TI  - Nurses are ideally placed to become specialists in allergy treatment.

PMID- 9197755
TI  - A street with characters. Interview by Janet Snell.

PMID- 9197756
TI  - Self-development for women in the NHS.
AB  - Training in the NHS in many careers, including nursing, does not routinely
      include preparation for management. This article looks at how a group of women in
      different disciplines in one NHS trust used the Astra programme from the equal
      opportunities unit at the NHS Executive as a means of developing their managerial
      careers. After taking part in the four-month programme, participants reported
      greater self-confidence, increased assertiveness and a greater sense of clarity
      about this career development.

PMID- 9197757
TI  - Screening for cervical cancer.
AB  - As part of a continuing series on how the work of pathology laboratories
      contributes to patient care, this article looks at the Papanicolaou (Pap) or
      cervical smear test, which involves the microscopical examination of cells
      recovered by scraping the surface of the cervix. The incidence, causes and
      aetiology are described and the organisation of cervical screening is shown.
      Finally, the range of findings from a positive smear test is explained.

PMID- 9197758
TI  - Meeting the health care needs of people with learning disabilities.
AB  - This article looks at the findings of a study on how primary health care teams
      saw the health care needs of people with learning disabilities and how those
      needs were being met. Among the issues discussed is the significance of relevant
      education in an interdisciplinary setting and the potential shift of some
      specialist community learning disability nurses to the primary health care team.

PMID- 9197759
TI  - Pain relief in childbirth.
AB  - This article looks at the research into pain relief for labouring women and
      concludes that there is a long way to go before most midwives can claim their
      practice is based on reliable evidence.

PMID- 9197760
TI  - Think ahead to minimise risks of midwifery care.

PMID- 9197761
TI  - Death in the family: helping with pet bereavement.

PMID- 9197762
TI  - Animal action stations.

PMID- 9197763
TI  - Chronic obstructive pulmonary disease. The role of the nurse.

PMID- 9197764
TI  - Many roads to midwifery.

PMID- 9197765
TI  - Compensation payment to former general secretary of the Royal College of Midwives
      Julia Allison.

PMID- 9197767
TI  - The proliferation of professors.

PMID- 9197766
TI  - The milky way.

PMID- 9197768
TI  - A singular campaign.

PMID- 9197769
TI  - Broadmoor has faced another inquiry.

PMID- 9197770
TI  - Fighting shy.

PMID- 9197771
TI  - Dobson's choice.

PMID- 9197772
TI  - Danger: bully at work.

PMID- 9197773
TI  - A special kind of courage.

PMID- 9197774
TI  - Your country needs you.

PMID- 9197775
TI  - Who wants to be a nurse?

PMID- 9197776
TI  - Young people at breaking point.

PMID- 9197778
TI  - A cut too far?

PMID- 9197777
TI  - The coffee professional.

PMID- 9197779
TI  - Blood money.

PMID- 9197780
TI  - In search of the pioneers of nurse-led care.
AB  - Nurse-led services are becoming more common in the UK. The first of three
      articles comparing developments in the USA and the UK, this looks at the origins
      of nurse-led units to discover what lessons may be learnt for the changes that
      have affected the Loeb Center in New York, a pioneer in the field.

PMID- 9197781
TI  - Methods of gastric decontamination.
AB  - Gastric emptying may not be the most appropriate way to decontaminate a person
      who has self-poisoned. Other methods, including emetics, cathartics and the use
      of activated charcoals, may be more appropriate in some circumstances.

PMID- 9197782
TI  - Epilepsy: the most common serious neurological condition.
AB  - This article looks at the diagnosis and management of epilepsy. The seizures
      associated with this condition are described and the classification is
      highlighted. Finally, the treatment is explained. A second article which looks at
      the nurse's role in caring for people with epilepsy and a patient's experience
      will be published July 2.

PMID- 9197783
TI  - Chronic obstructive pulmonary disease.

PMID- 9197784
TI  - Nutrition and HIV infection.

PMID- 9197785
TI  - A healthy degree of success.

PMID- 9197786
TI  - Know how vitamins and minerals.
AB  - Children are potentially at risk of vitamin and mineral deficiency. Young
      children have high nutrient requirements relative to their body size but
      frequently are faddy eaters and have small appetites. In contrast, school age
      children usually have good appetites, but have freedom of choice over what they
      eat and consume more meals outside the home. Their food choices are increasingly
      affected by peer pressure and advertising. This is a concern, as their knowledge
      of nutrition is limited.

PMID- 9197787
TI  - Assessment and planning for older people.

PMID- 9197788
TI  - Bridging interdisciplinary expertise with interdisciplinary research.

PMID- 9197789
TI  - Pulmonary aspiration in hospitalized adults.
AB  - Until recent years, pulmonary aspiration attracted remarkably little clinical
      investigation. Although aspiration was considered a common occurrence in
      hospitalized individuals, with serious and even fatal consequences, clinicians
      had limited scientific data to guide practice. Consequently, approaches to this
      problem were based largely on unsystematic observations, intuition, and
      tradition. Recent investigations on the subjects of aspiration have increased our
      understanding of patients at risk for aspiration, the value of diagnostic
      methods, and the efficacy of interventions to prevent or limit aspirations.
      Results of these studies call to question many time-honored adages and practices.
      Considerable uncertainty remains and more investigation is necessary before
      management decisions can be characterized clearly and clinical strategies
      defined. This review focuses on pulmonary aspiration and enteral feeding in the
      critically ill adult. Factors implicated in aspiration in this population are
      highlighted and evidence to support the application of interventions prescribed
      commonly is presented.

PMID- 9197790
TI  - Aspiration in a patient receiving enteral nutrition.
AB  - This case was selected to illustrate the advantages of an interdisciplinary team
      approach when the aspiration risks of enteral tube feeding are examined for
      patients with multisystem involvement. The case reviews a 79-year-old widowed
      woman with a cervical 6 to 7 spinal cord injury requiring mechanical ventilation
      and enteral feeding. The patient had multiple complications that prolonged her
      hospital course and required interdisciplinary involvement of medical, nutrition,
      nursing, respiratory, and speech pathology services. After an initial stay at
      another hospital, she was admitted to Providence Saint Joseph Medical Center
      (PSJMC) Acute Rehabilitation and Intensive Care Units. The patient was
      transferred home with PSJMC Home Health Services, and her case was part of a
      continuous quality improvement (CQI) project population group of ventilator
      dependent patients. The purpose of the interdisciplinary CQI team was to enhance
      nutrition intervention, improve patient outcomes, and reduce costs. This teaching
      case has added to the body of information being evaluated by the CQI team on
      nutrition intervention of ventilator-dependent patients.

PMID- 9197791
TI  - Nutrition risk classification: a reproducible and valid tool for nurses.
AB  - BACKGROUND: Incorporating the nursing staff to assist with the screening process
      on admission will allow patients who are at nutritional risk to be assessed by
      registered dietitians earlier in their hospital stay. The goal of this study was
      to develop an objective, valid, reproducible nutrition screen for use by
      registered nurses (RNs) to allow for nutrition classifications of hospitalized
      patients. METHODS: The current nursing admission assessment form was modified to
      contain questions on weight loss history, percentage of ideal body weight, and
      alterations in dietary intake and gastrointestinal function. Assessments were
      completed within 48 hours of admission. On the basis of the answers to these
      questions, patients were classified as "at nutritional risk" or "low nutritional
      risk." In phase 1, to assess reproducibility of the form, a prospective study
      between staff RNs and a nutritionist was undertaken on 186 consecutive adult
      admissions. Nutrition screening and classification was done independently by both
      practitioners. In phase 2 of the study, prospective validation of the form
      contrasting prealbumin (PAB) levels with RN nutritional risk classification (n =
      56) was investigated. RESULTS: Interobserver agreement of nutrition
      classification between RN and nutritionist was 97.3% (p = .95). Twenty-nine
      patients were classified at low nutritional risk (27 normal PAB and 2 low PAB);
      27 patients were classified as at nutritional risk (16 normal PAB and 11 low PAB)
      (chi 2 = 8.9, p < .003, power 0.8). The sensitivity of the tool was 84.6%.
      CONCLUSION: To our knowledge, this is the first nutrition screening tool designed
      for staff RNs that has been tested for both validity and reproducibility.

PMID- 9197792
TI  - Serum triglycerides of breast milk-fed very-low-birth-weight infants.
AB  - Normative triglyceride levels were obtained from eighty-five infants weighing <
      1500 g. At least 80% of their nutritional intake was their own mother's breast
      milk. Triglyceride levels did not correlate with birth weight, gestational age,
      volume of milk fed, age in days, or use of milk fortifier. The 95th percentile
      triglyceride value was 2.5 mmol/L. Assuming that breast milk-fed infants have
      triglyceride in the normal range, the acceptable limit of triglyceride values in
      very-low-birth-weight infants receiving i.v. lipids could be revised upward to
      2.5 mmol/L.

PMID- 9197793
TI  - The effect of changing the total parenteral nutrition order form on resident
      physician ordering behavior.
AB  - The quality assurance process at Scott and White Hospital, Temple, Texas,
      identified a marked variation in total parenteral nutrition (TPN) prescriptions
      compared with recommendations by the Nutrition Support Service (NSS). A TPN order
      form with additive guidelines was designed to assist physicians in ordering TPN
      specific to patient needs. The effect of the change was assessed by comparing 50
      TPN patients using the old form (1990) with 50 patients for whom the new form
      (1992) was used. The groups demonstrated no difference in demographics,
      mortality, length of stay, or biochemical parameters and were reflective of all
      TPN patients treated (1990, n = 280; 1992, n = 392). A significant decrease was
      noted in overfeeding of kilocalories when resident orders were compared with NSS
      recommendations (125% +/- 24% versus 110% +/- 29%, p = .017; and amino acids
      (120% +/- 32% versus 105% +/- 29%, p = .071, mean +/- SD). This resulted in a
      decrease of 8% in the cost of delivering a patient-day of TPN. We conclude that
      changing the TPN order form to a teaching vehicle results in decreased
      overfeeding and costs.

PMID- 9197794
TI  - Management of hyperglycemia in hospitalized patients receiving parenteral
      nutrition.

PMID- 9197795
TI  - Development of a blood glucose protocol using statistical quality control
      techniques.

PMID- 9197796
TI  - Enteral feeding set connectors and adapters. Association for the Advancement of
      Medical Instrumentation.
AB  - This standard provides safety requirements for enteral feeding set connectors and
      adapters.

PMID- 9197797
TI  - Perspectives of reproductive health.
AB  - This issue of Patient Education and Counseling is dedicated to reproductive
      health. The main focus is infertility as it is experienced in different of our
      world. In western societies, medical breakthroughs give couples with fertility
      problems a good chance to have a child. However, in many developing societies
      adequate medical treatment is only available for the upper classes, and many
      women keep going to traditional healers. In addition, the social consequences of
      childlessness are much greater than in western societies. Another focus of this
      issue is negative experiences regarding pregnancy. A very distressing experience
      is late pregnancy loss. Late pregnancy loss is different from infertility with
      respect to the tangibility of an object of grief, though it may also result in
      permanent childlessness. Other aspects of negative pregnancy experiences are
      exceptional physical reactions and recurrent induced abortions. Furthermore, two
      other elements of reproductive health are addressed in this issue: STD among
      female adolescents and gender aspects of gene technology. Finally, the
      ramifications of these various aspects of reproductive health on education and
      counseling are discussed.

PMID- 9197798
TI  - Psychosocial adjustment to unsuccessful IVF and GIFT treatment.
AB  - Twenty-one couples for whom in vitro fertilisation (IVF) or GIFT treatment failed
      were followed-up 15-30 months after treatment and compared with 20 couples for
      whom IVF had been successful. Current mental health status, quality of life and
      marital adjustment were assessed via standardised questionnaires. In addition,
      couples' experiences of IVF/GIFT treatment were explored via a semi-structured
      interview. Questionnaire results showed that unsuccessful IVF/GIFT recipients
      cannot be distinguished from general population norms. However, these couples
      reported more emotional distress relative to those whom treatment had worked and
      females in particular indicated a lower quality of life. Couples who had at least
      one child prior to IVF/GIFT treatment tended to show greater emotional distress
      at follow-up. Both groups gave similar accounts of the positive and negative
      aspects of IVF/GIFT treatment, but the unsuccessful group felt less supported by
      the IVF Unit staff and were less satisfied with the counseling they received. The
      data indicate that post-treatment counseling may be particularly important for
      facilitating positive reconstructions of the IVF experience when treatment is
      unsuccessful.

PMID- 9197799
TI  - Choices and motivations of infertile couples.
AB  - When couples are confronted with infertility they may choose among several
      options: medical help, adoption, fostering, alternative medicine and focusing on
      other life goals. The frequency of choices and motivations for these options were
      investigated among 131 infertile couples. Husbands and wives answered a
      structured questionnaire. The medical option was chosen in more than 80% of the
      cases. Also, this choice is made very quickly. Other options were considered at a
      later time, and chosen much later than the medical option. The most frequently
      mentioned motive for seeking help is the desire to have a child. This motive is
      reported in all forms of help seeking Motives for medical consultation are often
      seeking information, understanding the cause of infertility and physical
      complaints. Altruistic motives are rather important when considering adoption,
      and very important when considering foster-care.

PMID- 9197800
TI  - Infertility in the Gambia: traditional and modern health care.
AB  - In order to understand the problems of unwanted infertility in a country--the
      Gambia--where the desire for children and the fertility is very high, a
      population-based survey was undertaken. All infertile women in 24 randomly
      selected enumeration areas were assessed. The study included a review of the
      problems faced and coping mechanisms employed by infertility clients and types of
      health care available for infertile couples in the different types and levels of
      the formal and traditional health system. Half of the infertile couples failed to
      seek formal health care, and they have to reach a certain level of care in order
      to properly managed. Alternative care is often sought. Child fostering is also a
      frequent solution to childlessness. In-depth interviews revealed that traditional
      care like healers and spiritual leaders are frequently consulted long before
      formal health care. This delay could be a problem in those cases where
      infertility is caused by infections.

PMID- 9197802
TI  - Gene technology: also a gender issue. Views of Dutch informed women on genetic
      screening and gene therapy.
AB  - The reported research was conceived as a pilot study to explore the views of
      women on the implications of the analysis of the human genome. The data were
      gathered by interview and questionnaire from a group of Dutch women, most likely
      to have an informed opinion. However, even women who were assumed to be informed
      express a serious lack of knowledge. Nevertheless, they mention a whole range of
      problematic issues. Overall, women are likely to think that gene technology does
      affect them differently than it does men. They draw attention to the social
      reality of women's lives, mentioning the greater responsibility of mothers for
      the embryo and childbirth and pointing to the fact that women are subjected to
      more complicated and painful examinations. In the public debate attentional for
      gender implications of gene technology is lacking. A plea is made to improve the
      quality of the debate by integrating sex and gender specific issues.

PMID- 9197803
TI  - The grief of late pregnancy loss.
AB  - We studied 46 women who had an ultrasound diagnosis of a lethal fetal anomaly
      (gestational age > or = 24 weeks). Shortly after the diagnosis, 45% of these 46
      women showed severe psychological instability established by a consensus
      diagnosis. Three months later, this percentage had diminished significantly to
      22%. The total GHQ-28 score revealed that after 4 years, 11 out of the 29
      remaining participants (38%) had a score of 5 or more, which indicated a
      clinically significant degree of general psychological distress. Depression and
      despair measured with the Perinatal Grief scale, did not decrease significantly
      over the 4-year period. Women with a strong disposition towards feelings of
      inadequacy or 'neuroticism', measured with the Dutch Personality Questionnaire,
      displayed significantly more intense grief reactions than women without such a
      strong disposition. The implications of our study are that in the face of
      (threatened) late pregnancy loss, medical care should include (i) paying
      attention to the need for medical information and emotional support and (ii)
      performing psychosocial screening of women identified as showing signs of
      inadequacy.

PMID- 9197801
TI  - Social and cultural aspects of infertility in Mozambique.
AB  - Findings of an anthropological study of socio-cultural aspects of infertility
      among members of the matrilineal ethnic group Macua in the north of Mozambique
      are presented. Infertile women apply various strategies to have a child.
      Traditional healers are visited much more often than the modern hospital, and the
      explanations the infertile women themselves give for their infertility more often
      originated from the traditional healers than from the hospital staff. Almost all
      of the interviewed women commit adultery in the hope to conceive. Some of them
      apply fostering as a partial solution for childlessness. The Macua infertile
      women experience various consequences due to their infertility, of which
      exclusion from certain social activities and traditional ceremonies is perceived
      as a very problematic one. The matrilineal kinship system means that the husband
      and his family do not mistreat and repudiate her. Infertility must be considered
      as a serious reproductive health problem in Mozambique. For the long term
      preventive measures may be more influential than curative one. The findings of
      this study can be used to elaborate culturally sensitive health education
      programmes.

PMID- 9197804
TI  - Clinical experience with patients suffering from hyperemesis gravidarum (severe
      nausea and vomiting during pregnancy): thoughts about subtyping of patients,
      treatment and counseling models.
AB  - The medical and psychological treatment of hyperemesis gravidarum (HG) is
      generally acknowledged as being difficult. It is also recognized that the somatic
      changes during pregnancy play a role in the process of HG and that psychosocial
      factors are of particular importance. The following issues have been studied:
      psychosocial stressors; personality disorders; coping mechanisms and stress
      tolerance. The reviewed studies mention many different causes of HG. Some produce
      symptoms in certain women and some will not. As a result of clinical experience
      and observation during several years treating women with HG from a broad social,
      cultural and ethnic background in a large inner-city general hospital, we have
      been able to identify several subgroups of HG patients according to personality
      pathology, psychiatric symptoms and psychosocial stress factors. Accurate
      assessment is necessary in order to be able to tailor the interventions to the
      characteristics and needs of the individual patient. For the various subgroups
      different treatment strategies are recommended.

PMID- 9197805
TI  - The role of condom motivation education in the reduction of new and reinfection
      rates of sexually transmitted diseases among inner-city female adolescents.
AB  - The purpose of this study was to document the effectiveness of small group condom
      motivation education in reducing new and reinfection rates of sexually
      transmitted diseases (STD) among female teenagers. Two hundred and five (205)
      female adolescents (age 13-20) with a current STD were studied at two sites of a
      Teen Health Clinic. There were 86 teens in the Study Group and 119 in the
      Comparison Group. Patients were sampled from December 1992 to July 1993. The
      patients in the Study Group received a condom motivation class given by the
      clinic STD educator in small groups of four or more adolescents. The Comparison
      Group, comparable in age and ethnicity, received treatment for their STD but did
      not participate in condom motivation classes. All teens were given treatment and
      condoms. The sample was followed for 6 months. The total number of patients
      returning with new infections was 21 (14.7%). The total number of patients with
      reinfections was 14 (9.8%). There were no significant differences between the
      Study and Comparison Group on return rates, new and reinfection rates or on any
      socio-demographic variables. The comparison of these groups suggests that a
      specific condom motivation class has minimal effectiveness in urban teens.
      However, almost 70% of the teens returned to the clinic for their scheduled
      visits. It is suggested that adolescent clinics which combine family planning and
      STD treatment services maintain high client enrollment and therefore may be ideal
      locations to initiate new and continuous interventions for condom use especially
      for high risk teens.

PMID- 9197807
TI  - Sacred cows.

PMID- 9197806
TI  - Multiple induced abortions: Danish experience.
AB  - Experience with 50 first time aborters, 50 second time aborters, and 50 third
      time aborters residing in an urban area of Copenhagen suggests that women having
      a repeat abortion are more similar than dissimilar to women having a first
      induced abortion. There were no differences in socioeconomic status, educational
      level, or stated reasons for choosing abortion (usually socioeconomic and family
      considerations). Though similar to first and second time aborters in their life
      situations and greater contraceptive risk-taking, third timers seemed to become
      pregnant more readily. They were also less willing to be interviewed. Related
      studies and suggestions for postabortion counseling are discussed.

PMID- 9197808
TI  - Persistent potassium problems.

PMID- 9197809
TI  - Speaking out, taking risks.

PMID- 9197810
TI  - What about home care?

PMID- 9197811
TI  - Are opioids right for chronic nonmalignant pain?

PMID- 9197814
TI  - Breaking through the barriers to domestic violence intervention.

PMID- 9197815
TI  - Hyperkalemia.

PMID- 9197816
TI  - Back to basics: helping families cope with type I diabetes.

PMID- 9197817
TI  - Clinical snapshot. Cardiogenic shock.

PMID- 9197818
TI  - A nurse explores the Internet.

PMID- 9197819
TI  - How to safely clean surgical instruments.

PMID- 9197820
TI  - Talking about death with a dying child.

PMID- 9197821
TI  - Treatment of multiple lesions of Bowen disease with isotretinoin and interferon
      alfa. Efficacy of combination chemotherapy.

PMID- 9197822
TI  - The Americans With Disabilities Act and dermatologists.
AB  - The passage and implementation of the Americans With Disabilities Act of 1990
      (ADA) has established certain rights in law for persons with disabilities,
      including patients with skin disease. For workers in workplaces employing more
      than 15 workers, management may not exclude a worker from a job unless it can be
      objectively demonstrated that their skin disease will make it impossible for them
      to perform the essential functions of the job. Employers, at their expense, are
      now required to provide those disabled with skin disease with reasonable
      accommodation to allow them to perform their jobs while having their skin
      impairment. Unless the skin impairment can be shown to place the worker or their
      fellow workers at material risk to their health, the employer may not exclude
      them from working--even if the employer is concerned that it may make their skin
      disease worse. The act applies both to new employees and those acquiring
      disabling skin disease who are employed and wish to stay at work or return to
      work. Arbitration of dispute between employees and management are the
      responsibility of the Equal Employment Opportunities Commission (EEOC), a federal
      agency responsible for the legislation.

PMID- 9197823
TI  - Persistence of T-cell clones in psoriatic lesions.
AB  - BACKGROUND: We previously demonstrated a clonal dominance in the V beta 13.1
      messages isolated from the lesional CD8+ T cells of psoriasis vulgaris, which
      suggested an interaction of V beta 13.1+ CD8+ T cells with skin antigens.
      OBJECTIVES: To determine whether the clonality observed accurately reflected a
      clonal population of infiltrating T cells or was skewed by an overabundance of
      messages from a small number of cells, and to extend our study of V beta gene
      usage by lesional CD8+ T cells to 9 new patients. DESIGN: Case study. SETTING:
      Patients were enrolled at the Psoriasis Research Institute in Palo Alto, Calif,
      and samples were analyzed at The Immune Response Corporation in Carlsbad, Calif.
      MAIN OUTCOME MEASURES: For the 2 previous patients, skin samples were sorted
      directly for V beta 13.1+ T cells, for which the T-cell receptors were sequenced.
      For the 9 new patients, CD8+ T cells were sorted and their T-cell receptor V beta
      gene usage measured using semiquantitative polymerase chain reaction with V beta
      specific primers. RESULTS: The directly sorted V beta 13.1+ T cells exhibited
      clonal dominance in both patients. The dominant V beta 13.1 clone in each patient
      was the same as that found in the previous 2 biopsy specimens for which CD8+ T
      cells were sorted. Additionally, in 8 of the 9 new patients examined, we again
      found a preferential usage of V beta 3 and/or V beta 13.1 genes by the lesional
      CD8+ T cells. CONCLUSIONS: The clonality, which was found in the V beta messages
      of the sorted CD8+ T cells, accurately reflects the dominance of these clones in
      the infiltrating T cells. Moreover, the persistence in the same patient of the
      same clone for as long as 15 months and the overrepresentation of V beta 3 and/or
      V beta 13.1 in lesional CD8+ T cells in the new patients examined support the
      pathogenic role of T cells bearing these V betas.

PMID- 9197824
TI  - Acitretin therapy is effective for psoriasis associated with human
      immunodeficiency virus infection.
AB  - OBJECTIVE: To determine the safety, tolerability, and effectiveness of a newer
      retinoid, acitretin, as monotherapy for psoriasis associated with human
      immunodeficiency virus infection (PS-HIV). DESIGN: Pilot investigation. SETTING:
      An academic medical center. PATIENTS: Eleven patients selected from volunteers
      with PS-HIV were enrolled in a 20-week treatment protocol. Two patients
      discontinued participation in the study because of worsening psoriasis; a third
      patient was unable to continue treatment after having a myocardial infarction,
      presumably unrelated to acitretin therapy. INTERVENTION: Each patient received an
      optimized dose of acitretin during the period of observation. Clinical and
      laboratory assessments were performed every 2 weeks during the trial. MAIN
      OUTCOME MEASURES: The Psoriasis Area and Severity Index was used to assess the
      clinical response to treatment. To monitor for toxic drug effects, a panel of
      laboratory parameters, including complete blood cell count, biochemistry profile,
      urinalysis, HLA typing, skin biopsy for histological examination, and T-cell
      counts, was performed. RESULTS: Six (54%) of 11 patients with PS-HIV achieved
      good to excellent responses using acitretin monotherapy. Four patients (36%)
      achieved complete clearing. There was no evidence of a correlation between the
      pretreatment measures of immunosuppression and the therapeutic response.
      Parameters of immunosuppression were not exacerbated by acitretin therapy.
      CONCLUSIONS: Acitretin is a safe and effective treatment for PS-HIV. Both skin
      and joint manifestations of PS-HIV responded to acitretin therapy in most
      patients. Optimal results were achieved with a dose of 75 mg/d. The adverse
      effects were moderate and well tolerated. Acitretin does not appear to have
      immunosuppressive properties. A formal randomized clinical trial is warranted.

PMID- 9197825
TI  - Relationship between the in vivo localization and the immunoblotting pattern of
      anti-basement membrane zone antibodies in patients with bullous pemphigoid.
AB  - OBJECTIVE: To compare the localization of anti-basement membrane zone (BMZ)
      antibodies bound in vivo with the antigenic specificities of circulating anti-BMZ
      antibodies in patients with bullous pemphigoid (BP). DESIGN: Comparison of the
      results of an examination of the skin specimens of the patients using direct
      immunoelectron microscopy and direct immunofluorescence on 1-mol/L sodium
      chloride-split skin with the results of an analysis of the corresponding serum
      samples using the immunoblot technique. SETTING: Immunodermatology department in
      a teaching hospital. PATIENTS: Thirty-six patients with typical BP and
      circulating anti-BMZ antibodies. RESULTS: Serum samples from 22 patients with BP
      indicated only BP antigen 1 in the results of immunoblot analysis. Using direct
      immunofluorescence, an analysis of the peribullous skin samples obtained from
      these 22 patients showed deposits of IgG exclusively located along the epidermal
      side of sodium chloride-split skin; the results of direct immunoelectron
      microscopic examination showed deposits of IgG located on the intracellular
      portion of hemidesmosomes in 18 (82%) of these 22 specimens, whereas 4 biopsy
      specimens had linear IgG deposits located both intracellularly and
      extracellularly along the keratinocyte plasma membrane. The results of immunoblot
      analysis of the serum samples from 5 patients with BP indicated BP antigen 2
      alone; the results of direct immunoelectron microscopic examination of
      peribullous skin samples from these 5 patients showed linear intracellular and
      extracellular deposits along the keratinocyte membrane, corresponding to an
      epidermal fluorescence labeling pattern of peribullous sodium chloride-split skin
      in 2 patients and a combined (dermal and epidermal) pattern in 3 patients.
      CONCLUSION: The 2 different patterns of reactivity of anti-BMZ antibody deposits
      bound in vivo closely corresponded to the antigenic specificities indicated in
      the corresponding serum samples of the patients. These results are in accordance
      with those previously obtained in vitro and argue for identical binding profiles
      of circulating antibodies that are bound in vivo in BP.

PMID- 9197826
TI  - Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A
      pilot dose-ranging study.
AB  - OBJECTIVE: To examine the safety and efficacy of photodynamic therapy using
      topical 5-aminolevulinic acid (ALA) and red light to treat actinic keratoses
      (AKs). DESIGN: Actinic keratoses were treated with topical ALA (concentrations of
      0%, 10%, 20%, or 30%) under occlusion for 3 hours. Before photodynamic therapy,
      sites were examined for fluorescence. Sites were irradiated with an argon pumped
      dye laser (630 nm) at fluences of 10 to 150 J/cm2. SETTING: Academic medical
      center. PATIENTS: Forty patients with 6 clinically typical, previously untreated
      AKs per patient. MAIN OUTCOME MEASURE: Complete resolution and decrease in lesion
      area of the AK relative to baseline evaluated at weeks 1, 4, 8, and 16. RESULTS:
      Three hours after ALA administration, lesions showed moderate red fluorescence.
      Cutaneous phototoxic effects, localized erythema and edema, peaked at 72 hours.
      Patients experienced mild burning and stinging during light exposure. Eight weeks
      after a single treatment using 30% ALA, there was total clearing of 91% of
      lesions on the face and scalp and 45% of lesions, on the trunk and extremities.
      No significant differences were observed in clinical responses with treatment
      using 10%, 20%, or 30% ALA. All concentrations of ALA were more effective than
      treating AKs with vehicle and light. CONCLUSIONS: Topical photodynamic therapy
      with ALA is an effective treatment of typical AKs. Complete clearing of
      nonhypertrophic AKs can be achieved with 10%, 20%, or 30% ALA that is easily
      tolerated by the patient. Lesions on the face and scalp are more effectively
      treated than lesions on the trunk and extremities. Hypertrophic AKs did not
      respond effectively.

PMID- 9197827
TI  - Trends in the population-based incidence of squamous cell carcinoma of the skin
      first diagnosed between 1984 and 1992.
AB  - OBJECTIVE: To examine the incidence of first diagnosis of invasive squamous cell
      carcinoma (SCC) of the skin over time. DESIGN: Retrospective, population-based
      incidence study. SETTING: Enumerated, geographically isolated, semiurban
      population served by the Mayo Clinic and its affiliated hospitals and the Olmsted
      Medical Center, including its affiliated hospital in Rochester, Minn. METHODS:
      Using the Rochester Epidemiology Project databases that capture virtually all
      medical care provided to the residents of Rochester, we identified and reviewed
      records of all documented residents in whom histologically proven, invasive SCC
      of the skin was first diagnosed between 1984 and 1992. Age and sex stratum
      specific rates were calculated, and age-adjusted rates observed over time for
      individuals aged 35 years or older were analyzed using Poisson regression.
      Adjusted rates were compared with the results of other studies. RESULTS: Review
      of 1630 records identified 511 incidence cases of SCC. Tumors located on the head
      and neck accounted for 66.4% of tumors in females and 72.9% in males. The annual
      age- and sex-specific incidence rates per 100,000 increased from 0 cases among
      males aged 0 to 14 years to 1286.0 cases among males aged 85 years or older. Over
      time, the annual age-adjusted incidence rates per 100,000 females rose from 46.5
      (95% confidence interval [CI], 32.4-60.6) for the 1984 to 1986 period to 99.6
      (95% CI, 80.4-118.7) for the 1990 to 1992 period and were 71.2 (95% CI, 61.7
      80.8) overall. The corresponding rates for males were 125.9 (95% CI, 95.3-156.4),
      191.0 (95% CI, 156.9-225.0), and 155.5 (95% CI, 137.0-174.0). The age- and sex
      adjusted SCC incidence rates for the period from 1987 to 1989 and 1990 to 1992
      exceeded those for the period from 1984 to 1986 (P = .03 and P < .001,
      respectively). Our age-adjusted rates for SCC were within the ranges seen in
      other white populations from temperate climates. CONCLUSION: The frequencies of
      first diagnosis of SCC are increasing at rates beyond those explainable by
      demographic shifts alone.

PMID- 9197828
TI  - The histopathology of closed and open comedones of Favre-Racouchot disease.
AB  - OBJECTIVE: To determine the distinction between a comedo and an infundibular cyst
      of Favre-Racouchot disease. SETTING: A university hospital. PATIENTS: From the 8
      patients included in the study, 19 cysts and comedones were evaluated. MAIN
      OUTCOME MEASURE: The distinguishing features between the cysts and comedones of
      Favre-Racouchot disease. RESULTS: All lesions were histologically
      indistinguishable from the primary comedones of acne vulgaris, except for the
      presence of a marked actinic elastosis in the surrounding dermis. The presence of
      a variable number of hair shafts and an abundant amount of bacteria, which was
      positive in the results of Gram staining and periodic acid-Schiff reaction and
      intermingled with sebum and eosinophilic laminated horny material within the
      dilated infundibulum, characterizes a comedo and differentiates it from an
      infundibular cyst. CONCLUSIONS: The cysts and comedones of Favre-Racouchot
      disease are closed and open comedones. They can be easily differentiated from an
      infundibular cyst by the histopathologic features rather than by the connection
      to the surface.

PMID- 9197829
TI  - Pustular and erythrodermic psoriasis complicated by acute respiratory distress
      syndrome.
AB  - BACKGROUND: The pustular and erythrodermic types of psoriasis have been
      associated with a number of systemic complications, including congestive heart
      failure and pneumonia. Acute respiratory distress syndrome (ARDS) refers to acute
      noncardiogenic pulmonary edema with hypoxemia of various causes and has been
      attributed to pulmonary capillary leak. Recently, 4 cases of generalized pustular
      or erythrodermic psoriasis have been described associated with a pulmonary
      capillary leak syndrome. OBSERVATIONS: We describe 2 additional patients, 1 with
      pustular and erythrodermic psoriasis and 1 with erythrodermic psoriasis; who
      developed ARDS. Radiographic findings, pulmonary capillary wedge pressures,
      echocardiograms, and, in one case, an open lung biopsy specimen, were consistent
      with the diagnosis of ARDS. In neither case could we document any of the common
      causes of acute respiratory failure. CONCLUSIONS: Generalized pustular and
      erythrodermic psoriasis may be complicated by ARDS. The pathogenesis of this
      complication is unclear, but proinflammatory cytokines may be involved.

PMID- 9197830
TI  - Epiluminescence microscopy. A new approach to in vivo detection of Sarcoptes
      scabiei.
AB  - BACKGROUND: The usual methods of scabies diagnosis include microscopic
      identification of the mites and their eggs and feces in skin scrapings. In many
      cases, the results of microscopic examination can be negative owing to the low
      number of parasites present in the cornified layer. Epiluminescence microscopy
      (ELM) is an in vivo technique that allows a detailed inspection of the skin, from
      the surface to the superficial papillary dermis. This is where the scabies mite
      lives. In this study, we evaluate the applicability and the usefulness of ELM for
      in vivo diagnosis of scabies. OBSERVATIONS: Sixty-five (93%) of 70 cases of
      scabies showed small, dark, triangular structures at the sites examined with ELM.
      A subtle linear segment seen below the base of the triangle was made visible by
      the presence of small air bubbles. Together, both structures resembled a jet with
      contrail. On traditional microscopic examination of the scrapings, we verified
      that the triangular structure corresponded to the pigmented anterior section of
      the mite in all cases. The linear segment observed on ELM was thought to be the
      burrow of the mite along with its eggs and fecal pellets. The cases in which the
      results of a first ELM examination were negative demonstrated positive results on
      a second ELM examination carried out 20 days later. CONCLUSION: Epiluminescence
      microscopy is a very useful tool for in vivo diagnosis of scabies because it
      permits Sarcoptes scabiei detection in only a few minutes, with no discomfort to
      the patient and with a very low number of false-negative results.

PMID- 9197831
TI  - Rheumatoid neutrophilic dermatitis.
AB  - BACKGROUND: Rheumatoid neutrophilic dermatitis (RND) is a recently recognized,
      rare cutaneous manifestation of rheumatoid arthritis. It occurs in patients with
      severe rheumatoid arthritis and is typically asymptomatic. Rheumatoid
      neutrophilic dermatitis was originally described by Ackerman in 1978. Since that
      time, 8 patients with this disease have been described in the literature.
      OBSERVATIONS: We report 2 cases of RND. Findings of skin biopsy specimens from
      both patients revealed characteristic signs of dermal leukocytosis and
      leukocytoclasia without vasculitis. The pathogenesis of the neutrophilic
      infiltrate is unclear. Processes that may play a role in the pathogenesis of RND
      include immune complex activations, cell adhesion and migration, and cytokine
      release. CONCLUSIONS: Rheumatoid neutrophilic dermatitis falls into the spectrum
      of neutrophilic vascular reactions described by Jorizzo and Daniels. Although
      early reports suggest that prominent leukocytoclasia is not a feature of RND, our
      findings confirm the observations of Lowe et al that leukocytoclasia can be seen
      in RND and may be striking. It is important for dermatologists to be aware of
      this rare manifestation of rheumatoid arthritis.

PMID- 9197832
TI  - Palpable migratory arciform erythema. Clinical morphology, histopathology,
      immunohistochemistry, and response to treatment.
AB  - BACKGROUND: Palpable migratory arciform erythema is clinically characterized by
      sharply circumscribed, infiltrated erythematous patches that tend to spread
      irregularly, resulting in arciform morphologic features. The histopathologic
      features are characterized by a patchy inflammatory perivascular and periadnexal
      T-lymphocytic infiltrate throughout the dermis. The disease runs a chronic course
      and is rarely described in the literature. OBSERVATION: Three middle-aged
      patients of both sexes had palpable migratory arciform erythema with 1, several,
      or multiple lesions on the trunk. There was a dense perivascular and periadnexal,
      predominantly lymphocytic infiltrate of the reticular dermis without any
      interstitial distribution of inflammatory cells. Absence of mucin deposits and
      plasma cells was a striking feature. The immunohistochemical profile showed an
      infiltrate dominated by T cells of polyclonal origin. In addition, polyclonal B
      cells and histiocytes were present in small numbers. In all 3 cases, oral
      antibacterial treatment resulted in a complete (2 patients) or temporary (1
      patient) resolution of skin lesions. CONCLUSIONS: Palpable migratory arciform
      erythema shows distinctive differences in clinical and pathological features and
      treatment in contrast to other diseases with cutaneous lymphocytic infiltrates,
      including lymphocytic infiltration of Jessner and Kanof. Therefore, it is likely
      a distinct disease entity.

PMID- 9197833
TI  - Endogenous retroviral sequences in the pathogenesis of systemic autoimmune
      disease.
AB  - OBJECTIVES: To update information on endogenous retroviral sequences and discuss
      their role in systemic autoimmune disease. DATA SOURCES: Articles retrieved after
      MEDLINE search and personal communications and cooperation with the Institute of
      Virology. DATA SYNTHESIS: There are 2 modes of pathogenetic mechanisms through
      which endogenous retroviral sequences could cause systemic autoimmune disease:
      expression of endogenous retroviral gene products sharing antigenic determinants
      with cellular proteins; and activation or destruction of cellular genes as a
      consequence of insertional mutagenesis. Both mechanisms have been demonstrated in
      vitro and in vivo in animal models. CONCLUSION: Investigations on endogenous
      retroviral sequences in humans may offer new insights into the pathogenesis of
      autoimmune disease.

PMID- 9197835
TI  - Vesicobullous lesions in a child. Bullous pemphigoid (BP).

PMID- 9197834
TI  - Papules and vesicles in an 18-month-old boy. Eosinophilic pustulosis (EP) of
      childhood.

PMID- 9197837
TI  - Multiple papules on the elbows. Congenital osteoma cutis.

PMID- 9197838
TI  - Immunopathogenesis of psoriasis. The road from bench to bedside is a 2-way
      street.

PMID- 9197839
TI  - Hormones, immunology, nevi, and melanoma.

PMID- 9197840
TI  - Latent Epstein-Barr virus infection is frequently detected in subcutaneous
      lymphoma associated with hemophagocytosis but not in nonfatal cytophagic
      histiocytic panniculitis.

PMID- 9197841
TI  - Anetoderma of prematurity.

PMID- 9197842
TI  - Tufted angioma: is it the same as angioblastoma (Nakagawa)?

PMID- 9197843
TI  - Effect of growth hormone therapy on melanocytic nevi in survivors of childhood
      neoplasia.

PMID- 9197844
TI  - Favre-Racouchot syndrome: a case for smokers' comedones.

PMID- 9197845
TI  - Hospitalization for skin disease improves quality of life.

PMID- 9197846
TI  - Low-calcium dialysis in calciphylaxis.

PMID- 9197847
TI  - Surgery in India.
AB  - Surgical practice in India is mostly managed by the central and state governments
      and is totally government financed, offering free medical aid. However, with the
      economic growth and affluence of the middle-class population in urban areas, more
      and more hospitals, nursing homes, and clinics managed by the private sector are
      arising in cities and towns. Privately owned hospitals are built and managed by
      large industrial houses and trusts. It is essential, according to government
      directives, for these hospitals to have certain numbers of general beds that will
      provide for the economically weaker sections of the population. Medical insurance
      is popular amongst the urban population; in addition to well-established
      insurance companies, many new medical service reimbursement organizations are
      forming. Surgical care standards are uniformly high in the larger teaching
      institutions and hospitals run by the private sector in major cities in India, in
      which superspecialty surgical care that meets worldwide standards is available in
      addition to general surgical care. These hospitals are manned by surgeons holding
      master's degrees in general surgery, superspecialties, and subspecialties. In the
      hospitals and dispensaries in rural areas, only basic surgical facilities are
      available; for major surgical procedures, the patients are referred to the
      closest urban hospitals. Therefore, the government of India is placing more and
      more emphasis on building hospitals that offer better surgical facilities away
      from the cities and towns. A diploma course in surgery is run by the National
      Board of Surgery, and these diplomates are encouraged to practice more in rural
      areas and small hospitals. Economic constraints and the population explosion are
      the biggest hurdles to progress in surgical care, teaching, and research
      activities. With the advancement in education and growth of the economy, more and
      more multinationals are walking into the field of medical care, which is proving
      to be a great boon and providing a rapid increase in the health care expansion in
      this country. The World Health Organization and the World Bank are providing
      considerable aid for disease prevention, health care provision, and research
      activities.

PMID- 9197848
TI  - The tyranny of capitation. Health care in the belly of the beast.

PMID- 9197849
TI  - Laparoscopic paraesophageal hernia repair.
AB  - BACKGROUND: Paraesophageal hernias require surgery to avoid potentially serious
      complications. OBJECTIVE: To evaluate paraesophageal hernia repair using the
      laparoscopic approach. DESIGN: Case series. SETTING: University hospital and
      foregut testing laboratory. SUBJECTS: Sixty-five consecutive patients (mean age,
      63.6 years; range, 26-90 years). Preoperative evaluation included barium
      esophagogram, endoscopy, esophageal manometry, and 24-hour pH monitoring. OUTCOME
      MEASURES: Operative complications, postoperative morbidity, follow-up symptoms
      (53 patients; mean, 18 months; range, 2-54 months) and barium esophagogram (46
      patients). RESULTS: Fifty-six patients (86%) had a type III hernia and 9 (14%)
      had a type II hernia. Twenty (65%) of 31 patients who underwent pH monitoring had
      a positive 24-hour pH score, and 24 (56%) of 43 patients who underwent manometry
      had an incompetent lower esophageal sphincter. Four patients had a gastric
      volvulus and 21 patients had more than 50% of their stomach in the chest. All
      patients underwent hernia reduction, crural repair, and fundoplication (64 Nissen
      procedures and 1 Toupet procedure). The average duration of surgery was 2 hours.
      There were 2 conversions: gastric perforation and a difficult dissection because
      of a large fibrotic sac. Other complications, all managed intraoperatively, were
      2 gastric perforations and bleeding in 6 patients. Average length of hospital
      stay was 2 days (range, 1-23 days). Early re-operation was required in 3
      patients: slipped Nissen; small-bowel obstruction due to trocar-site hernia; and
      organo-axial rotation with gastroduodenal obstruction. Four patients required
      esophageal dilatation after surgery. Forty-nine of 53 patients available for long
      term follow-up were satisfied with the results of surgery. Time to full recovery
      was 3 weeks (range, 1 week to 2 months). Seven of 46 patients experienced small
      type I hernias observed on routine follow-up esophagograms. CONCLUSIONS: Most
      paraesophageal hernias are type III. A concomitant antireflux procedure is
      recommended. Paraesophageal hernias can be managed successfully by the
      laparoscopic route with good outcome.

PMID- 9197850
TI  - Endotracheal intubation in the field improves survival in patients with severe
      head injury. Trauma Research and Education Foundation of San Diego.
AB  - OBJECTIVE: To measure the effect of prehospital endotracheal intubation on
      outcome in patients with severe head injury and the percentage of these patients
      intubated in the field under existing protocol. DESIGN: Retrospective case
      control study. SETTING: Countywide urban trauma system. PATIENTS: Trauma patients
      with blunt injury and scene Glasgow Coma Score of 8 or less, transported by
      ground ambulance with advanced life support capabilities from January 1, 1991, to
      December 31, 1995. Severe head injury was defined as head or neck Abbreviated
      Injury Scale score of 4 or greater. Isolated severe head injury was defined as
      head or neck Abbreviated Injury Scale score of 4 or greater with no other
      Abbreviated Injury Scale component greater than 3. One thousand ninety-two
      patients met initial criteria; of these, 671 had severe head injury, and 351 had
      isolated severe head injury. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Mortality and functional status sufficient for discharge to home. RESULTS: Field
      intubation was associated with significant decreases in mortality from 36% to 26%
      in the full study group, from 57% to 36% in patients with severe head injury, and
      from 50% to 23% in patients with isolated severe head injury. Rate of discharge
      to home was unaffected by field intubation. Between 50% and 60% of study patients
      were intubated under current paramedic protocol, compared with intubation rates
      of 85% to 92% for similar patients transported by aeromedical teams operating
      under expanded indications for intubation. CONCLUSIONS: Prehospital endotracheal
      intubation was associated with improved survival in patients with blunt injury
      and scene Glasgow Coma Score of 8 or less, especially those with severe head
      injury by anatomic criteria. Broadening indications for intubation by paramedical
      personnel has great potential to improve outcome in patients with severe head
      injury.

PMID- 9197851
TI  - Is cryosurgical ablation appropriate for treating hepatocellular cancer?
AB  - OBJECTIVE: To examine the feasibility and efficacy of cryosurgical ablation as
      treatment for patients with cirrhosis with unresectable hepatocellular carcinoma.
      DESIGN: Retrospective case series. SETTING: A tertiary public hospital and a
      cancer center. PATIENTS: Twelve patients with cirrhosis with hepatocellular
      carcinoma (stage II, 2; stage III, 1; stage IVA, 7; stage IVB, 2). INTERVENTIONS:
      Cryosurgical ablation of all identifiable tumors. Nine patients treated with
      curative intent were included in the survival analysis, and 3 were treated for
      palliation. Five patients were treated with preoperative intra-arterial
      chemoembolization. MAIN OUTCOME MEASURES: Perioperative complications and the
      effects of tumor stage and chemoembolization were examined. Patient survival and
      disease-free interval were calculated by life-table analysis. RESULTS: No
      perioperative deaths occurred and 1 patient had 2 postoperative complications:
      pneumonia and biloma. The mean survival has been 19 months after cryosurgical
      ablation and 29 months after diagnosis. Three of the 9 patients treated with
      curative intent died with recurrence at a mean of 17 months after cryosurgical
      ablation. Four patients are alive with recurrence at a mean of 19 months after
      cryosurgical ablation and 38 months after diagnosis. Two patients with stage II
      disease have no evidence of recurrence 10 and 32 months after cryosurgical
      ablation. CONCLUSIONS: Cryosurgical ablation is feasible and safe for treatment
      of hepatocellular carcinoma in patients with cirrhosis. The technique is
      primarily palliative but may provide a possibility of cure in patients with lower
      stage disease.

PMID- 9197852
TI  - The impact of regionalization on a surgery program in the Canadian health care
      system.
AB  - OBJECTIVE: To examine the impact of the regionalization of health care on the
      provision of surgical services in the Capital Health Region (Edmonton) of the
      province of Alberta. DESIGN: A 4-year retrospective descriptive analysis using
      data from the Canadian Institute for Health Information and from the Capital
      Health Region data banks. SETTING: To control health care costs, the provincially
      funded health care system in Alberta reformed its governance structure and
      service provision model. We studied community hospitals and an academic health
      sciences center. PATIENTS: All patients undergoing surgical care in the region.
      INTERVENTIONS: Regionalization of the organizational structure with the
      elimination of hospital boards, consolidation of services on specific sites
      within the regional system, and a major reduction in funding. OUTCOME MEASURES:
      Inpatient and day surgery procedure volumes, average length of hospital stay,
      relative value units, bed use, and mortality. RESULTS: The Capital Health Region
      has a population of 723,000 people, with 5 acute care institutions. Eighteen
      clinical programs now provide care through 2 referral hospitals and 3 community
      health centers. The reduction in operating dollars for this region was $167.1
      million from fiscal years 1992-1993 to 1996-1997. Redistribution of surgical
      services occurred on July 1, 1995, resulting in an 18% inpatient bed reduction.
      Regionally, the number of acute care beds has declined from 2.25 to 1.47 per 1000
      population (P < .001). Bed use has fallen from 637 to 442 inpatient days per 1000
      population (P < .001). The surgery volume (1995-1996) was 44770 procedures (
      3.1%). Redistribution of surgical services into high- and low-acuity settings has
      resulted in most surgeons working on 2 sites. Overall average length of hospital
      stay has decreased significantly (P < .001); however, it has increased, together
      with the average relative value units, in the institutions caring for patients
      with high-acuity surgical illnesses. Mortality remains unchanged. CONCLUSIONS:
      Regionalization and funding reductions within the surgical program in the Capital
      Health Region have resulted in a small reduction in surgical volumes. There have
      been major changes in service provision and the way surgeons practice.

PMID- 9197853
TI  - Current results of surgical therapy for chronic mesenteric ischemia.
AB  - BACKGROUND: Although recognition of chronic mesenteric ischemia has increased in
      recent years, this disorder has continued to present diagnostic and therapeutic
      challenges. OBJECTIVE: To examine the modern results of surgical
      revascularization for chronic mesenteric ischemia. DESIGN: Retrospective review.
      SETTING: University medical center. PATIENTS: The management of 24 consecutive
      patients (mean +/- SEM age, 58 +/- 3 years; 5 men, 19 women) who were undergoing
      surgical treatment of chronic mesenteric ischemia between 1986 and 1996 was
      reviewed. INTERVENTION: Surgical mesenteric revascularization. MAIN OUTCOME
      MEASURES: Postoperative course, long-term graft patency rate, and long-term
      symptom-free survival rate. RESULTS: The most frequent presenting symptoms were
      postprandial abdominal pain (18 patients [75%]) and weight loss (14 patients
      [58%]). Less specific complaints included nausea and vomiting (8 patients [33%]),
      diarrhea (7 patients [29%]), and constipation (4 patients [17%]). Atherosclerotic
      risk factors were common, including tobacco use (20 patients [83%]), coronary
      artery disease (10 patients [42%]), and hypertension (10 patients [42%]). The
      cause was identified as atherosclerosis in 21 patients, median arcuate ligament
      compression in 2 patients who were monozygotic twins, and Takayasu arteritis in 1
      patient. Lesions were localized to all 3 major visceral vessels (celiac artery,
      superior mesenteric artery [SMA], and inferior mesenteric artery) in 8 patients,
      celiac artery and SMA in 13, SMA alone in 2, and SMA and inferior mesenteric
      artery in 1. Seventeen patients underwent antegrade reconstructions from the
      supraceliac aorta to the SMA and/or celiac artery; 7 patients underwent
      revascularization by use of a retrograde bypass that originated from the
      infrarenal aorta or a prosthetic graft. There were no perioperative deaths
      although 1 patient died in the hospital 6 weeks after early graft failure and
      sepsis (overall in-hospital mortality, 4%). Follow-up ranged from 3 months to 10
      years (median, 2.4 years). The mean +/- SEM 5-year primary graft patency rate, as
      objectively documented by use of contrast angiography or duplex scanning in 19 of
      24 patients, was 78% +/- 11%. Primary failure was documented in 3 patients (at 3
      weeks, 5 months, and 7 months). Two patients required a thrombectomy; 1 of these
      patients subsequently died of an intestinal infarction. The mean +/- SEM 5-year
      survival rate by use of life-table analysis was 71% +/- 11%. No patient with a
      patent graft experienced a symptomatic recurrence. CONCLUSIONS: Chronic
      mesenteric ischemia is usually a manifestation of advanced systemic
      atherosclerosis. Symptoms almost always reflect midgut ischemia in the
      distribution of the SMA. An antegrade bypass from the supraceliac aorta can be
      performed with acceptable operative morbidity and is currently the preferred
      reconstructive technique. Surgical revascularization affords long-term symptom
      free survival in a majority of patients with chronic mesenteric ischemia.

PMID- 9197854
TI  - Blood transfusion. An independent risk factor for postinjury multiple organ
      failure.
AB  - OBJECTIVE: To determine if blood transfusion is a consistent risk factor for
      postinjury multiple organ failure (MOF), independent of other shock indexes.
      DESIGN: A 55-month inception cohort study ending on August 30, 1995. Data
      characterizing postinjury MOF were prospectively collected. Multiple logistic
      regression analysis was performed on 5 sets of data. Set 1 included admission
      data (age, sex, comorbidity, injury mechanism, Glasgow Coma Scale, Injury
      Severity Score, and systolic blood pressure determined in the emergency
      department) plus the amount of blood transfused within the first 12 hours. In the
      subsequent 4 data sets, other indexes of shock (early base deficit, early lactate
      level, late base deficit, and late lactate level) were sequentially added.
      Additionally, the same multiple logistic regression analyses were performed with
      early MOF and late MOF as the outcome variables. SETTING: Denver General
      Hospital, Denver, Colo, is a regional level I trauma center. PATIENTS: Five
      hundred thirteen consecutive trauma patients admitted to the trauma intensive
      care unit with an Injury Severity Score greater than 15 who were older than 16
      years and who survived longer than 48 hours. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: The relationship of blood transfusions and other shock indexes with the
      outcome variable, MOF. RESULTS: A dose-response relationship between early blood
      transfusion and the later development of MOF was identified. Despite the
      inclusion of other indexes of shock, blood transfusion was identified as an
      independent risk factor in 13 of the 15 multiple logistic regression models
      tested; the odds ratios were high, especially in the early MOF models.
      CONCLUSIONS: Blood transfusion is an early consistent risk factor for postinjury
      MOF, independent of other indexes of shock.

PMID- 9197855
TI  - Prognostic factors with the use of the transjugular intrahepatic portosystemic
      shunt for bleeding varices.
AB  - OBJECTIVES: To evaluate the outcome of patients undergoing the transjugular
      intrahepatic portosystemic shunt (TIPS) procedure for bleeding esophageal varices
      and to outline the factors affecting outcome. DESIGN: Uncontrolled,
      nonrandomized, retrospective study. SETTING: A 320-bed university-associated
      urban emergency adult hospital. PATIENTS: Thirty-three patients undergoing TIPS
      procedures for bleeding esophageal varices with at least 18 months of follow-up.
      Five patients (15%) had Child class B disease and 28 (85%) had Child class C
      disease. The mean transfusion requirements were 12.6 U of red blood cells, 18 U
      of fresh-frozen plasma, and 7 U of platelets. The mean portosystemic gradients
      before and after the initial TIPS procedure were 18 and 7 mm Hg, respectively.
      OUTCOME MEASURES: The incidence, time and causes of death, and recurrent variceal
      hemorrhage were correlated with various clinical and laboratory factors. RESULTS:
      By 18 months after the TIPS procedure, 16 patients (48%) died of rebleeding or
      hepatic failure. Subsequent upper gastrointestinal tract bleeding occurred in 14
      patients (42%). Of 8 in whom occlusion or stenosis of the TIPS was promptly
      corrected, all 8 survived. Of 6 in whom occlusion or stenosis of the TIPS was not
      corrected, 5 (83%) died. Laboratory values (mean +/- SD) predictive of death
      before 18 months (compared with those of patients alive at 18 months) included a
      low initial serum albumin level (22 +/- 4 vs 29 +/- 5 g/L; P < .001); an
      increased initial total bilirubin level (68 +/- 75 vs 34 +/- 20 mumol/L [4.0 +/-
      4.4 vs 2.0 +/- 1.2 mg/dL]; P = .001), and an elevated prothrombin time after
      attempts at correction (18.0 +/- 3.4 vs 14.6 +/- 1.2 seconds; P < .001).
      CONCLUSIONS: The TIPS procedure in patients with Child class C alcoholic
      cirrhosis was associated with a high incidence of death or rebleeding within 18
      months. Prompt correction of TIPS abnormalities in patients with rebleeding
      increased survival. The albumin, bilirubin, and prothrombin time values obtained
      before performance of the TIPS procedure were predictive of outcome.

PMID- 9197856
TI  - Protective effect of hypothermia and left heart bypass on spinal ischemia in the
      dog.
AB  - OBJECTIVE: To test the hypothesis that systemic hypothermia (SH) to 30 degrees C
      in combination with partial left heart bypass (PLHB) at either a high or low
      distal arterial perfusion pressure (DAPP) following 45 minutes of cross-clamp
      (XC) occlusion of the thoracic aorta will protect against clinical and
      histological spinal cord ischemia in the dog. DESIGN: A blinded, prospective,
      randomized, and controlled experimental trial. SETTING: Tertiary care center
      animal laboratory. PARTICIPANTS: Seventeen adult mongrel dogs. INTERVENTIONS: The
      animals were randomized into 5 groups: control group 1: XC plus no protection (n
      = 3); control group 2; XC plus systemic normothermia plus PLHB, with a DAPP less
      than 20 mm Hg (n = 3); treatment group 1: XC plus systemic normothermia plus
      PLHB, with a DAPP greater than 20 mm Hg (n = 3); treatment group 2: XC plus SH
      plus PLHB, with a DAPP greater than 20 mm Hg (n = 3); treatment group 3: XC plus
      SH plus PLHB, with a DAPP less than 20 mm Hg (n = 5). MAIN OUTCOME MEASURES:
      Clinical and histological neurological injury evaluation by separate blinded
      observers. RESULTS: Control animals were neurologically and histologically
      ischemic. Treatment animals were neurologically and histologically normal.
      Partial left heart bypass with a DAPP greater than 20 mm Hg prevented paraplegia,
      with either systemic normothermia or SH. Systemic hypothermia plus PLHB, even
      with a DAPP less than 20 mm Hg, protected against spinal cord ischemia during
      thoracic aortic occlusion. CONCLUSION: Systemic hypothermia to 30 degrees C
      combined with PLHB at either a high or low DAPP prevented spinal cord ischemia
      following thoracic aortic XC occlusion in our canine model and merits clinical
      trial in patients.

PMID- 9197857
TI  - Laparoscopic splenectomy for immune thrombocytopenic purpura.
AB  - OBJECTIVE: To evaluate laparoscopic splenectomy as a treatment of immune
      thrombocytopenic purpura (ITP). DESIGN: Retrospective review of 18 patients
      followed up from 1 to 30 months. SETTING: Referral center using community
      hospital. PATIENTS: Consecutive series of patients undergoing laparoscopic
      splenectomy for ITP. INTERVENTION: Laparoscopic splenectomy. MAIN OUTCOME
      MEASURE: Surgical and hematologic results. RESULTS: Eighteen patients underwent
      laparoscopic splenectomy for ITP. All procedures were completed laparoscopically.
      There was no perioperative mortality. Pancreatitis developed in 1 patient (6%);
      17 (94%) of 18 patients responded to splenectomy. The mean platelet count
      increased from 29 x 10(9) to 461 x 10(9)/L after laparoscopic splenectomy and
      stabilized at 327 x 10(9)/L (mean follow-up period, 15 months). Mean (+/- SEM)
      operative blood loss was 214 +/- 52 mL, necessitating no transfusions. Mean
      hospital stay was 2 days (range, 1-7 days). Most patients tolerated a liquid diet
      the day of the operation and a solid diet the next day. Parenteral narcotic usage
      averaged 12.3 morphine equivalent units, and 6 patients (33%) required no
      parenteral analgesia. An accessory spleen was identified in 1 patient (6%). Mean
      (+/- SEM) operative time was 130 +/- 8 minutes and was significantly less in the
      second half of our experience (117 vs 144 minutes, P = .04). CONCLUSIONS:
      Laparoscopic splenectomy is safe and effective for the management of ITP and
      allows rapid recovery. With increasing experience, operative times decrease.
      Laparoscopic splenectomy should be the treatment of choice for patients with ITP
      who require splenectomy.

PMID- 9197858
TI  - Posttraumatic empyema. Risk factor analysis.
AB  - BACKGROUND: Empyema remains a distressing complication after thoracic injury.
      OBJECTIVE: To identify high-risk factors associated with the development of
      empyema. DESIGN: Retrospective cohort review. SETTING: University hospital, level
      I trauma center. PATIENTS: Trauma patients who required tube thoracostomy (TT)
      between January 1, 1991, and November 31, 1993 (n = 584). METHODS: Data
      (demographic characteristics, injuries, chest x-ray film reports, and setting of
      TT) were assessed using a stepwise logistic regression analysis to identify risk
      factors associated with the development of post-traumatic empyema. RESULTS:
      Empyema that required decortication developed in 25 patients (4%). Factors
      predictive of development of empyema were retained hemothorax (odds ratio, 12.5;
      95% confidence interval, 0.96-163), pulmonary contusion (odds ratio, 6.3; 95%
      confidence interval, 1.53-25.8), and multiple chest tube placement (odds ratio,
      2.5; 95% confidence interval, 1.91-3.28); factors not predictive of empyema were
      severity of injury, mechanism of injury, setting in which TT was performed,
      number of days chest tubes were in place, and antibiotic drugs at the time of TT.
      CONCLUSIONS: The extent of pulmonary injury (pulmonary contusion) is an important
      predictor of empyema development. Previously implicated factors such as setting
      in which a TT was performed and mechanism of injury did not correlate with the
      development of posttraumatic empyema. Based on the results of our study, we
      recommend early drainage of the pleural space with video-assisted thoracoscopic
      techniques in patients at risk of empyema, which may spare them the morbidity of
      a thoracotomy.

PMID- 9197859
TI  - Blunt intestinal injury in children. Diagnostic and therapeutic considerations.
AB  - OBJECTIVES: To identify computed tomographic (CT) findings in children who have
      experienced blunt trauma and who have known intestinal injuries and to correlate
      these findings with the findings of the initial physical examination. DESIGN: A
      retrospective review of children (aged < 18 years) known to have an intestinal
      injury as a consequence of blunt trauma. SETTING: A university-affiliated
      children's hospital with a level 1 pediatric trauma center. PATIENTS: Children
      younger than 18 years who were admitted for examination of injuries or for
      management of complications related to intestinal injuries. INTERVENTIONS:
      Clinical and radiographic evaluation and laparotomy for intestinal injuries other
      than duodenal hematoma. MAIN OUTCOME MEASURES: The identification and correlation
      of relevant findings during the physical examination, on the CT scan, and during
      surgery. The assessment of intervals from injury to diagnosis and intervention
      and the description of associated injuries. RESULTS: Twenty-two patients
      sustained intestinal injuries as a result of blunt trauma. Most (15) of the
      patients were passengers injured in motor vehicle crashes; 14 of these patients
      were wearing seat belts. Focal blows to the abdomen from bicycle handlebars,
      hockey sticks, or falls onto blunt objects were implicated in the remaining
      patients. For 19 of the 22 patients, the initial physical examination was
      conducted at Cardinal Glennon Children's Hospital, St Louis, Mo, and 18 of the 19
      patients underwent a concurrent CT evaluation. Peritonitis was found in 5 of
      these 18 patients. Tenderness on physical examination was noted in 9 of the 18
      patients (tenderness was not noted in 3 patients, and 1 patient had unreliable
      examination findings due to a cervical spinal cord injury). Computed tomographic
      findings of pneumoperitoneum and extravasation of enteral contrast material were
      uncommon but diagnostic (in 5 patients). Free fluid in the pelvis in the absence
      of a solid organ injury, bowel wall thickening, and fluid-filled loops of bowel
      were more frequently useful signs of possible intestinal injury (in 9 of the 18
      patients) and led to earlier exploration when used in conjunction with physical
      examination as an indication for surgery. Most injuries were treated with
      segmental resection or suture repair, but enterostomies were required in 2
      patients. Complications (i.e., the need for enterostomy and fascial dehiscence)
      were seen as a result of late or missed diagnosis, which could occur as late as 4
      to 6 weeks after injury as intestinal obstruction due to stricture. CONCLUSIONS:
      The initial physical examination findings and CT evaluation can independently
      identify the presence of intestinal injury in approximately 25% of cases. In the
      remainder of cases, the awareness of the more subtle findings of bowel injury on
      a CT scan can complement the physical examination findings and potentially lead
      to a more timely intervention for bowel injury.

PMID- 9197860
TI  - National treatment trends for ductal carcinoma in situ of the breast.
AB  - OBJECTIVE: To evaluate the national treatment trends for the management of ductal
      carcinoma in situ as related to the individual characteristics of patients and to
      the reporting of demographics. DESIGN: National Cancer Data Base review.
      PATIENTS: Patients (N = 39010) who were diagnosed as having ductal carcinoma in
      situ between 1985 and 1993. MAIN OUTCOME MEASURES: Treatment principles,
      including the use of breast-preserving surgery, axillary lymph node dissection,
      and radiotherapy, as related to the following variables: age, income level, and
      ethnicity of the patient; the tumor size, grade, and anatomical subsite; year of
      diagnosis; geographic location of treatment; and hospital type and caseload.
      RESULTS: During the 8 years of analysis, the use of breast preservation therapy
      increased from 31% to 54%. Treatment selection varied to some degree with each of
      the variables examined. Tumors with favorable sizes and grades were associated
      with increased rates of breast preservation and lower rates of axillary lymph
      node dissection and radiotherapy utilization. Overall, only 45% of the patients
      who were treated with breast preservation received adjuvant radiotherapy.
      However, during this study, radiotherapy utilization increased from 38% to 54%.
      Axillary lymph node dissection was performed in 49% of the patients with a 12%
      reduction in use over time. CONCLUSIONS: Breast-preserving surgery now accounts
      for more than half of all cases of ductal carcinoma in situ followed by the
      National Cancer Data Base. However, there still remains an inappropriately high
      rate of axillary lymph node dissection and a low rate of radiotherapy
      utilization. Clinical trial results and professional education should continue to
      optimize the management of patients with ductal carcinoma in situ.

PMID- 9197861
TI  - Optimal selective sentinel lymph node dissection in primary malignant melanoma.
AB  - OBJECTIVE: To determine the optimal approach of selective sentinel lymph node
      (SLN) dissection in primary malignant melanoma. DESIGN: Consecutive patient
      study. Prior to selective SLN dissection and wide local excision of the primary
      melanoma biopsy site, technetium Tc 99m sulfur colloid was injected intradermally
      around the primary melanoma or biopsy site to mark the SLN. Isosulfan blue
      (Lymphazurin, Hirsch Industries Inc, Richmond, Va) was injected at the primary
      biopsy site immediately before the surgical procedure. SETTING: Teaching hospital
      tertiary care referral center. MAIN OUTCOME MEASURES: Successful identification
      of SLNs being defined as positive for microscopic metastatic melanoma by blue dye
      staining, radioisotope uptake, or both. RESULTS: Selective intraoperative mapping
      by gamma probe and visualization of blue dye-stained SLN(s) resulted in a 98%
      (160/163) successful identification rate. Thirty patients (18.4%) had microscopic
      metastatic melanoma of the SLN(s), 22 of whom had subsequently completed
      lymphadenectomy. In 4 (18.2%) of these 22 patients, further microscopic
      metastatic disease was found in 1 of 8 nodes, 1 of 8 nodes, 1 of 28 nodes, and 1
      of 9 nodes. No notable complications were encountered. Five recurrent cases from
      patients with SLNs without microscopic metastatic melanoma (3.8%) and 2 from
      patients with SLNs with microscopic metastatic melanoma (6%) were found during a
      median follow-up period of 463 days. A second primary melanoma developed in 2
      patients; neither had no local recurrence. CONCLUSIONS: Sequential combination of
      preoperative lymphoscintigraphy and intraoperative mapping is a reliable way to
      identify regional SLN. The frequency of microscopic metastatic melanoma of the
      SLN(s) is 18.4%. Gamma-probe--guided resection minimizes the extent of lymph node
      dissection. Further follow-up is needed to assess the outcome of this group of
      patients for regional and systemic recurrences.

PMID- 9197862
TI  - Follicular and Hurthle cell thyroid neoplasms. Is frozen-section evaluation
      worthwhile?
AB  - OBJECTIVES: To determine whether (1) frozen-section (FS) evaluation of follicular
      and Hurthle cell thyroid neoplasms (FHCNs) is accurate, (2) FS aids in
      intraoperative decision-making, and (3) FS is cost-effective. DESIGN:
      Retrospective review of patient histories and FS and paraffin-embedded slides.
      Permanent histologic sections were considered the standard criterion. Follow-up
      was achieved in 92% of patients with a mean follow-up of 5.7 years. SETTING:
      Tertiary care referral center. PATIENTS: All patients undergoing thyroidectomy
      for a suspected FHCN between January 1, 1985, and December 31, 1994. Patients
      included were those whose condition was diagnosed as FHCN, either on FS,
      permanent histologic sections, or both. MAIN OUTCOME MEASURES: Sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of FS analysts were determined. Total adjusted hospital charges were compared for
      those undergoing 1 vs 2 cancer operations. Multivariate analyses were carried out
      to determine the optimal predictive model for follicular cancer. RESULTS: The
      study group included 1023 patients (737 women and 286 men), of whom 83 (8.1%)
      were diagnosed as having a malignant FHCN on permanent section. The diagnosis of
      malignant neoplasm was correctly established in 65 (78%) of the 83 patients on
      FS, thereby permitting definitive surgical management at the first operation.
      Sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy for FS diagnosis of malignant FHCN were 78%, 99%, 90%, 98%, and 98%,
      respectively. In a multivariate analysis, FS was the most significant variable
      predictive of malignant neoplasm. Approximately $400,000 was saved in hospital
      charges by the use of FS as a result of the elimination of many 2-stage
      operations. CONCLUSION: Frozen-section evaluation of FHCN can be performed with a
      high degree of accuracy, permitting considerable cost savings.

PMID- 9197864
TI  - On knowledge of regulations for clinical trials.

PMID- 9197863
TI  - Low-dose heparin thromboembolism prophylaxis.

PMID- 9197865
TI  - What should obstetricians be doing about the Barker hypothesis?

PMID- 9197866
TI  - Customised fetal growth assessment.

PMID- 9197867
TI  - Hypoxia-ischaemia and the developing brain: hypotheses regarding the
      pathophysiology of fetal-neonatal brain damage.

PMID- 9197868
TI  - Maternal birthweight and diet in pregnancy in relation to the infant's thinness
      at birth.
AB  - OBJECTIVE: To examine how maternal diet in pregnancy and parental body size and
      birthweight influence an infant's thinness at birth measured by a low ponderal
      index. DESIGN: An observational study of newborn infants and their parents.
      SETTING: Southampton, England. POPULATION: Five hundred and thirty-eight infants
      born at term. MAIN OUTCOME MEASURE: Ponderal index at birth. RESULTS: Women who
      had a high intake of carbohydrate in early pregnancy and a low intake of dairy
      protein in late pregnancy tended to have infants that were thin at birth (P =
      0.01 and P = 0.03, respectively, in a simultaneous analysis). Women who
      themselves had a low birthweight also tended to have thin infants, ponderal index
      falling from 28.3 kg/m3 to 26.2 kg/m3 as the women's birthweights decreased from
      more than 4.0 kg to 2.5 kg or less (P < 0.0001). Tall fathers had thin infants,
      but ponderal index was not related to the women's heights or the fathers'
      birthweights. CONCLUSION: These associations may reflect constraints on placental
      development imposed by a woman's nutrition in pregnancy and during her own
      intrauterine life. Effects of the father's height may be mediated through genetic
      influences on skeletal growth.

PMID- 9197869
TI  - Significance of low birthweight for gestational age among very preterm infants.
AB  - OBJECTIVE: To estimate the risk of specific adverse neonatal events resulting
      from the combined effects of prematurity and low birthweight in very preterm
      infants (delivered at 24-31 weeks of gestation). DESIGN: A cohort study of
      specific adverse neonatal events in preterm infants born at between 24 and 31
      weeks of gestation. SETTING: Pavia, Italy. POPULATION: Two hundred and thirty
      singleton infants with sonographically confirmed gestational age, delivered at 24
      to 31 weeks of gestation. METHODS: To evaluate the impact of a lower than
      expected birthweight on selected neonatal events independently of gestational
      age, we calculated birthweight standard deviation scores (differences between
      actual birthweight and fitted birthweight divided by fitted standard deviation)
      for each week of gestation. RESULTS: After adjustment for gestational age and
      other confounders, there was a significant linear trend relating a decreasing
      birthweight SDS to an increased likelihood of neonatal death, intraventricular
      haemorrhage, severe respiratory distress syndrome, and acidosis. Compared with
      infants with SDS > or = 0 (> or = 50th centile of birthweight), infants with
      birthweight SDS < -1 (< 16th centile) had increased odds for neonatal death [odds
      ratio (OR) 3.7, 95% confidence interval (CI) 1.42-9.6], grade III-IV
      intraventricular haemorrhage (OR 17.5, 95% CI 4.04-75.9), and neonatal acidosis
      (OR 3.22, 95% CI 1.41-7.4). The significance of birthweight SDS as a predictor of
      neonatal outcome, however, was lower than that of gestational age. CONCLUSIONS: A
      lower than expected birthweight affects the likelihood of several adverse
      neonatal events in very preterm infants. However, a decreasing birthweight SDS
      affects neonatal outcome less than decreasing gestation does.

PMID- 9197870
TI  - Transvaginal Doppler ultrasound of the uteroplacental circulation in the early
      prediction of pre-eclampsia and intrauterine growth retardation.
AB  - OBJECTIVE: To evaluate the predictive value of transvaginal Doppler ultrasound
      studies of the uterine and umbilical arteries in early pregnancy, in identifying
      pregnant women at risk of subsequently developing pre-eclampsia, or the delivery
      of a small for gestational age infant. DESIGN: A multivariate logistic regression
      of Z scores of Doppler indices obtained from the uterine and umbilical arteries
      of 652 women with singleton pregnancies at 12 to 16 weeks of gestation.
      Measurements included the presence or absence of a notch, bilateral (right and
      left waveform) notching, vessel diameter, the resistance index, the pulsatility
      index, time averaged mean velocity (cm/s), maximum systolic velocity (cm/s), and
      volume flow (mL/min). Stepwise logistic regression and multivariate analysis of
      all the parameters measured was used to construct several scoring systems. MAIN
      OUTCOME MEASURES: Pre-eclampsia, birthweight, preterm delivery. RESULTS: In women
      that developed complications, there was a trend towards increased resistance and
      reduced velocity and volume flow. If bilateral notches were present there was an
      increased risk of pre-eclampsia (odds ratio [OR] 21.99, 95% CI 6.55-73.79),
      premature delivery (OR 2.38, 95% CI 1.19-4.75), and the delivery of a small for
      gestational age baby (OR 8.63, 95% CI 3.95-18.84). Using multivariate analysis, a
      seven parameter model was selected (after removal of vessel diameter, uterine and
      umbilical resistance index). This model produces a scoring system with a
      sensitivity of 92.9% and a specificity of 85.1% for the prediction of pre
      eclampsia. A three parameter model (bilateral notches, uterine resistance index,
      umbilical pulsatility index) provides similar sensitivities, but lower
      specificities, when compared with the seven parameter model. CONCLUSION: These
      data indicate that there are differences in uterine and umbilical artery Doppler
      blood flow indices at 12 to 16 weeks, in pregnancies with a normal or complicated
      outcome. Scoring systems derived from multivariate analysis of Doppler indices
      demonstrate the potential of being able to identify, in early pregnancy, a group
      of women at increased risk of the subsequent development of pre-eclampsia,
      premature delivery, or the birth of a small for gestational age baby.

PMID- 9197871
TI  - 24-hour blood pressure monitoring to evaluate the effects of nifedipine in pre
      eclampsia and in chronic hypertension in pregnancy.
AB  - OBJECTIVE: To investigate the effect of 7 to 14 days of therapy with nifedipine
      (sustained-release preparation) on the 24-hour blood pressure patterns of
      pregnant women with pre-eclampsia or chronic hypertension, and to test the
      utility of blood pressure monitoring in modulating the timing and dosage of the
      drug. DESIGN: 24-hour automatic blood pressure monitoring of pregnant women with
      pre-eclampsia or chronic hypertension before and after nifedipine treatment.
      SETTING: Centre for Prevention, Diagnosis and Treatment of Hypertension in
      Pregnancy, University of Turin, Italy. POPULATION: Sixteen pregnant women with
      pre-eclampsia and 17 with chronic hypertension. METHODS: 24-hour blood pressure
      monitoring was performed before the beginning of the therapy and after 7 to 14
      days of treatment with sustained-release nifedipine. MAIN OUTCOME MEASURES:
      Chronobiological analysis of systolic and diastolic blood pressure values was
      performed; MESOR, amplitude, acrophase, hyperbaric index, percent time elevation
      and significance of rhythm were calculated before and after treatment. RESULTS:
      6336 blood pressure measurements were analysed. Systolic and diastolic MESOR
      values were significantly decreased after nifedipine treatment both in pre
      eclampsia and in chronic hypertension. However, the antihypertensive effect of
      nifedipine in pre-eclampsia was especially pronounced during evening and night,
      while in chronic hypertension it was more constant during the 24-hour period. 24
      hour blood pressure monitoring allowed adjustment, when necessary, to the timing
      and dosage of nifedipine in accordance with the blood pressure patterns of each
      patient, using the hyperbaric index and percent time elevation as objective
      parameters for the evaluation of treatment efficacy. CONCLUSIONS: 24-hour blood
      pressure monitoring is a good method to optimise treatment, and confirms that
      nifedipine is useful for the control of maternal blood pressure in pregnancy.

PMID- 9197872
TI  - Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised
      controlled trial.
AB  - OBJECTIVE: To determine whether antioxidant therapy alters the disease process in
      severe early onset pre-eclampsia, in support of the hypothesis that increased
      lipid peroxides and reactive oxygen species production-play an important role in
      the pathogenesis of the disease. DESIGN: Randomised, double-blind, placebo
      controlled trial. SETTING: Two tertiary care, referral hospitals in Johannesburg,
      South Africa. PARTICIPANTS: Women with severe pre-eclampsia diagnosed between 24
      and 32 weeks of gestation. INTERVENTION: Combined antioxidant treatment with
      vitamin E (800 IU/day), vitamin C (1000 mg/day), and allopurinol (200 mg/day).
      MAIN OUTCOME MEASURES:  PRIMARY OUTCOMES: 1. prolongation of pregnancy and 2,
      biochemical assessment of lipid peroxides and antioxidants. SECONDARY OUTCOMES:
      data on maternal complications, side effects of treatment, infant outcomes and
      regular assessment of haematologic and renal parameters. RESULTS: The proportion
      of women delivered within 14 days in the antioxidant group was 52% (14/27)
      compared with 76% (22/29) in the placebo group (relative risk 0.68, 95%
      confidence interval 0.45-1.04). One woman in each group had eclampsia. Eleven
      women (42%) in the antioxidant and 16 (59%) in the placebo group required two
      antihypertensives for blood pressure control. Trial medications were well
      tolerated with few side effects. Lipid peroxide levels were not significantly
      altered in the antioxidant and placebo groups. Serum uric acid levels decreased
      and vitamin E levels increased significantly. CONCLUSION: The results of this
      explanatory randomised trial do not encourage the routine use of antioxidants
      against pre-eclampsia. However, further research with modified strategies such as
      earlier initiation of therapy or different combinations seem worthwhile.

PMID- 9197873
TI  - A single cervical fetal fibronectin screening test in a population at low risk
      for preterm delivery: an improvement on clinical indicators?
AB  - OBJECTIVE: To assess the accuracy of a single cervical fetal fibronectin test to
      predict spontaneous preterm delivery in an unselected antenatal population.
      DESIGN: A prospective blind cohort study. SETTING: Antenatal clinic of a teaching
      hospital in a Brussels semiurban area. PARTICIPANTS: An unselected group of 170
      women followed at the antenatal clinic. METHODS: A single cervical sample was
      obtained between 24 and 33 completed weeks of pregnancy. The fibronectin test was
      compared with clinical evaluation and their predictive properties were assessed.
      RESULTS: Fifteen women were excluded from the analysis because of elective
      preterm delivery for medical indications or loss to follow up. Of the 155
      remaining women, nine (7%) had a spontaneous preterm delivery. For a single fetal
      fibronectin test, the sensitivity was 26.7%, the specificity 95.7%, and the
      positive and negative predictive values 40.0% and 92.4%, respectively. The
      likelihood ratio of a positive was similar to that of clinical predictors of
      preterm birth (LR = 6.2; 95% CI 2.0-19.6). Sensitivities were low for both
      clinical criteria and the fetal fibronectin test. CONCLUSIONS: Because of low
      sensitivity in a low risk population, screening for preterm delivery should not
      be based on the result of a single fetal fibronectin test alone. However, due to
      its high specificity the test might be useful in avoiding unnecessary medical
      intervention.

PMID- 9197874
TI  - Effects on bone mass after eight years of hormonal replacement therapy.
AB  - OBJECTIVE: The purpose of this randomised double-blind placebo-controlled study
      over two years followed by a six year open controlled extension phase was to
      investigate the effects of hormonal replacement therapy (HRT) both continuous
      combined HRT and sequential HRT) versus no treatment on lumbar spine bone mineral
      density (L-BMD) and distal forearm bone mineral content (F-BMC). Further, bone
      mineral density of the proximal femur, lateral spine, and distal forearm was
      studied after eight years. DESIGN: Prospective study of normal, early
      postmenopausal women, initially in a double-blind, placebo controlled study,
      subsequently an open, controlled investigation. SETTING: Clinical physiology unit
      of a general second degree referral hospital. SAMPLE: Seventy-three normal, early
      postmenopausal women (HRT n = .47; placebo/untreated n = 26). METHODS: Dual
      photon absorptiometry, dual X-ray absorptiometry, single photon absorptiometry.
      MAIN OUTCOME MEASURES: HRT resulted in a significantly (P < 0.001) higher mean L
      BMD after eight years, when it was 12.1% higher than the mean initial value and
      14.8% higher than the mean bone mineral density of the untreated group. L-BMD
      increased by 14.6% in women receiving continuous combined HRT compared with 11.1%
      in those on sequential HRT but intergroup differences were not statistically
      significant. Mean F-BMC measured with SPA decreased in the HRT group and in the
      placebo/untreated group by 0.2% and 14.8% (P < 0.001), respectively. However,
      after eight years mean F-BMC was 14.5% higher in the HRT group than in the
      placebo/untreated group. The study showed after eight years for all regions of
      the distal radius and ulna a significantly higher bone mineral density value
      compared with the placebo/untreated group (P < 0.001). An especially large effect
      of HRT was found on the bone mineral density of the vertebral body of the 3rd
      lumbar vertebra (L3), this one, measured by lateral scanning, being 18.7% higher
      than that of the placebo/untreated group. For the proximal femur, only the bone
      mineral density of Ward's triangle was significantly higher in the HRT group than
      in the placebo/untreated group. CONCLUSION: Eight years of treatment with HRT
      resulted in a significant, substantial gain of bone mineral density in the lumbar
      spine. The distal radius, ulna and Ward's triangle showed a significantly higher
      bone mineral density in the HRT group compared with the placebo/untreated group.

PMID- 9197876
TI  - A study of treatment failures following large loop excision of the transformation
      zone for the treatment of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To examine the long term efficacy of large loop excision of the
      transformation zone (LLETZ) in the treatment of cervical intraepithelial
      neoplasia (CIN) and to evaluate the relative diagnostic merits of colposcopy and
      cytology in the follow up of these women. DESIGN: A retrospective examination of
      cytology, colposcopy and histology records of the first 1000 women treated with
      LLETZ in Aberdeen from 1989 to 1991. SETTING: Colposcopy Clinic Aberdeen Royal
      Infirmary, Grampian Region, Scotland. RESULTS: Nine hundred and seventy-seven
      women (97.7%) were seen for follow up at least once and 317 were followed for as
      long as four years. This comprises 2812 woman years of follow up. The incidence
      of recurrent CIN was 27/1000 woman years and the cumulative rate of recurrence at
      four years was 10.1 per 100 women. Twenty-eight of the 59 women (47%) with
      abnormal colposcopy and proven CIN had a concurrent smear that did not show
      dyskaryosis. CONCLUSIONS: LLETZ is an effective from of treatment for CIN.
      Colposcopy was useful in the follow up of these women and expedited the treatment
      of persistent disease. We recommend that any follow up protocol should include a
      colposcopic assessment and cytological follow up for at least four years
      following treatment. Further data are required to determine the risk of
      recurrence beyond this time.

PMID- 9197875
TI  - Long-term influence of different postmenopausal hormone replacement regimens on
      serum lipids and lipoprotein(a): a randomised study.
AB  - OBJECTIVE: To assess the influence of three different postmenopausal hormone
      replacement therapies on levels of serum lipids and lipoprotein(a) [Lp(a)].
      DESIGN: Open, randomised, controlled study. PARTICIPANTS: One hundred and forty
      healthy, early postmenopausal women. INTERVENTIONS: The women were randomised to
      receive continuous 17 beta-oestradiol, either orally (2 mg daily; n = 35) or
      transdermally (50 micrograms daily; n = 35), plus 10 mg dydrogesterone daily for
      14 days of each 28-day cycle; or 2.5 mg tibolone daily (n = 35). Thirty-five
      untreated women acted as controls. MAIN OUTCOME MEASURES: Fasting blood samples
      were analysed at baseline, 6, 12 and 24 months for low-density lipoprotein (LDL)
      cholesterol, high-density lipoprotein (HDL)-cholesterol, very low density
      lipoprotein (VLDL), total cholesterol, triglycerides, lipoprotein(a)[Lp(a)],
      apolipoproteins A-1, A-2 and B, fibrinogen, and antithrombin factor III. RESULTS:
      At 24 months oral oestradiol increased mean HDL cholesterol (7%; 95% CI 1-14),
      compared with no change in the transdermal group and a decrease of 26.8% in the
      tibolone group (95% CI 22.9-30.5); oral oestradiol decreased mean LDL cholesterol
      (11.8%; 95% CI 6.3-19), compared with no change in the tibolone group. Changes in
      apolipoprotein A-1 and B showed a similar pattern to HDL and LDL cholesterol,
      respectively. Oral oestradiol increased serum triglycerides (30%; 95% CI 18-42)
      after 24 months, compared with no change in the tibolone and transdermal
      oestradiol groups. Tibolone decreased serum Lp(a) by 36.6% after 24 months (95%
      CI 8.3-56.2), oral oestradiol decreased levels by 29.4% (95% CI 2-51.1), compared
      with no change in the transdermal oestradiol group. CONCLUSIONS: Oral and to a
      lesser extent transdermal oestradiol when sequentially combined with
      dydrogesterone, showed a beneficial influence on serum lipids regarding the
      cardiovascular disease risk, which was not seen with tibolone. The significance
      of Lp(a) levels on cardiovascular disease risk remains to be determined.

PMID- 9197877
TI  - Simultaneous effects of aneuploidy and oncogenic human papillomavirus on
      histological grade of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To investigate whether ploidy and oncogenic human papillomavirus types
      can be correlated with the histological grade of cervical intraepithelial
      neoplasia (CIN) in the same tissue sections. DESIGN: Histological data were
      obtained from 292 dysplastic lesions of the cervix and classified according to
      the CIN and the Bethesda terminologies. The samples were analysed using Feulgen
      stained image analysis cytometry for ploidy and Human papillomaviruses DNA typing
      by in situ hybridisation, respectively. SETTING: Colposcopy Clinic at Alfred
      Fournier Institute, Paris. POPULATION: Three hundred and forty women referred for
      an abnormal cervical smear. RESULTS: The ploidy data strongly segregate high
      grade from low grade squamous intraepithelial lesions (aneuploidy 78% versus 21%;
      P < 0.0001). There was a significant association between aneuploidy and the
      severity of the lesions (94% for CIN 3, 55% for CIN 2 and 14% for CIN 1; P <
      0.0001). Both classifications showed a significant association of histological
      grade with oncogenic human papillomavirus types (HPV 16-18-33; 20% in low grade
      and 78% in high grade squamous intraepithelial lesions, 31% and 75% in CIN 1 and
      CIN 3, respectively; P < 0.0001). The simultaneous effects of these viruses and
      ploidy demonstrate an association in aneuploid cells between the presence of
      oncogenic human papillomavirus types and histological grade (76% and 18% in high
      and low grade squamous intraepithelial lesions, respectively; P < 0.0001). Such
      an association was not observed in diploid cells (20% in both low and high grade
      squamous intraepithelial lesions). CONCLUSIONS: High risk human papillomavirus
      types do not exert and an independent effect on the histological grade of
      cervical intraepithelial neoplasia.

PMID- 9197878
TI  - The effect of long-term oestradiol implantation on bone mineral density in
      postmenopausal women who have undergone hysterectomy and bilateral oophorectomy.
AB  - Twelve women who had received oestradiol implantation on demand for at least 15
      years following hysterectomy with bilateral oophorectomy, underwent bone
      densitometry of hip and spine. Bone mass of hip and spine was significantly
      elevated above that of both the age matched mean to a degree hitherto
      undocumented. This suggests that oestrogen in high doses or over a long period
      may produce a true anabolic effect on bone mass.

PMID- 9197879
TI  - Urinary tract injuries during obstetric intervention.
AB  - A retrospective case record review of obstetric urinary tract injury in the
      Grampian region from 1976 to 1993 identified 16 cases of bladder injury (0.1 per
      1000 deliveries, 1.4 per 1000 caesarean sections and four cases of ureteric
      injury (0.03 per 1000 deliveries, 0.27 per 1000 caesarean sections). Diagnosis of
      bladder injury was immediate, but of ureteric injury often delayed. Although the
      injury rates are lower than previously reported and previously reported risk
      factors not confirmed, this audit has resulted in guidelines for junior staff,
      compliance with which will be monitored, and every case of urinary tract injury
      will be reviewed.

PMID- 9197880
TI  - Routine antenatal screening for syphilis in Lothian: a study of the results 1988
      to 1994.
AB  - A retrospective study was carried out of the cases of positive syphilis serology
      detected by routine antenatal screening within Edinburgh (and surrounding
      district) over the six years 1988 to 1994. The study demonstrated a low incidence
      of syphilis with only 15 pregnancies in 58,445 screened. In eight cases serology
      and history were suggestive of late latent syphilis and in the remainder of
      previous infection which had been treated. All women were delivered of liveborn
      infants at term without stigmata of congenital syphilis. Lack of identifiable
      risk factors in women with positive serology suggests that routine rather than
      selective screening should continue.

PMID- 9197881
TI  - Comparison of second trimester biometry in singleton and twin pregnancies
      conceived with assisted reproductive techniques.
AB  - The objective of this study was to investigate the size of singleton vs twin
      pregnancies at the time of a second trimester dating scan. The analysis included
      86 infants from 63 pregnancies achieved with assisted reproductive techniques,
      comprising 40 singletons and 46 twins. Measurements of second trimester
      biparietal diameter (n = 85) and femur length (n = 74) were plotted against the
      precisely known gestational age. A common regression line was calculated for each
      parameter and the residuals for singletons and twins were compared. Gestational
      age and weight at birth were also analysed for each group. There was no
      significant difference between singletons and twins in biparietal diameter or
      femur length in second trimester. In contrast, twins had a lower mean
      birthweight, gestational age at birth, and weight-for-gestational age centile
      compared with singletons. Singleton babies from these pregnancies had an average
      birthweight centile of 49.8% (i.e. close to the median for spontaneously
      conceived pregnancies in our population). We concluded that the same pregnancy
      dating charts can be used for singletons and twins. At corresponding gestational
      age, twins are smaller than singletons at birth because of slower growth in the
      third trimester.

PMID- 9197882
TI  - Maternal serum free beta-hCG at 10 to 14 weeks of gestation in trisomic twin
      pregnancies.
AB  - Maternal serum free beta-hCG was measured at 10 to 14 weeks of gestation in 136
      normal twin pregnancies and in 12 twin pregnancies where one or both fetuses had
      trisomy 21. The values were compared with a normal range from 4181 singleton
      pregnancies. In the normal twins the median free beta-hCG (65 ng/mL) was about
      twice as high as in singletons (34 ng/mL z = -12.1, P < 0.0001). In the trisomy
      21 group the median free beta-hCG (95 ng/mL) was significantly higher than in
      normal twins (z = 2.1, P < 0.05). However, only one of the trisomic pregnancies
      had a level above the 95th centile. In twin pregnancies maternal serum free beta
      hCG at 10 to 14 weeks of gestation is unlikely to be useful in the prediction of
      fetal trisomy 21.

PMID- 9197883
TI  - Indicators of platelet turnover in thrombocytopenic infants.
AB  - Glycocalicin has been found to be a marker of increased platelet turnover, while
      interleukin-6 may be increased in response to thrombocytopenia. We used these
      markers to study the pathophysiology of thrombocytopenia in newborn infants. Cord
      blood platelet counts were obtained from 499 infants. Thrombocytopenic infants (<
      100,000/mm3) and a control group had ELISA assays for interleukin-6 and
      glycocalicin performed. The mean levels of glycocalicin and interleukin-6 were
      elevated in cord blood of thrombocytopaenic infants. Infants with intrauterine
      growth restriction and thrombocytopaenia had no detectable glycocalicin in their
      plasma, despite elevated levels of interleukin-6. This probably reflects impaired
      thrombopoiesis in these infants.

PMID- 9197884
TI  - Churg-Strauss disease: deterioration in a twin pregnancy. Successful outcome
      following treatment with corticosteroids and cyclophosphamide.

PMID- 9197885
TI  - Uterine carcinosarcoma in association with tamoxifen therapy.

PMID- 9197886
TI  - Survival of intrauterine twins and an interstitial singleton fetus from a
      heterotopic in vitro fertilisation-embryo transfer pregnancy.

PMID- 9197887
TI  - Missed abortion versus delayed miscarriage.

PMID- 9197888
TI  - Medico-legal aspects of ureteric damage during abdominal hysterectomy.

PMID- 9197889
TI  - Anal and urinary incontinence in women with obstetric anal sphincter rupture.

PMID- 9197890
TI  - Anal and urinary incontinence in women with obstetric anal sphincter rupture.

PMID- 9197891
TI  - Using a logistic model to identify women with first-trimester spontaneous
      abortion suitable for expectant management.

PMID- 9197892
TI  - Magnesium sulphate in the treatment of eclampsia and pre-eclampsia: an overview
      of the evidence from randomised trials.

PMID- 9197893
TI  - Antenatal testing for HIV: to opt in or opt out, that is the question.

PMID- 9197894
TI  - Protective effect of depot-medroxyprogesterone acetate on surgically treated
      uterine leiomyomas: a multicentre case-control study.

PMID- 9197895
TI  - Doctors leaving the training grades in obstetrics and gynaecology: a study of the
      years 1985 to 1988.

PMID- 9197896
TI  - Early prediction of pre-eclampsia by measurement of kallikrein and creatinine on
      a random urine sample.

PMID- 9197897
TI  - Borderline ovarian cancer, bilateral surgical castration, chemotherapy and a
      normal delivery after ovum donation and in vitro fertilisation-embryo transfer.

PMID- 9197898
TI  - The combat of non-compliance during prophylactic lithium treatment.
AB  - Non-compliance is the most frequent cause of recurrence during prophylactic
      lithium treatment and is associated with poor response and high levels of
      suicidality. Non-compliance is a complex phenomenon and may have a number of
      causes. When manic-depressive patients fare badly under the conditions of so
      called 'naturalistic' trials, this usually indicates that such conditions are
      inadequate for long-term maintenance treatment. Prophylactic lithium treatment
      must be accompanied by measures to sustain compliance and counteract drop-out,
      and these measures build on three cornerstones, namely information, support and
      supervision.

PMID- 9197899
TI  - Fertility in schizophrenia: results from a contemporary US cohort.
AB  - To investigate procreation in schizophrenia, as well as gender-related
      differences, female patients with schizophrenia (n = 79, DSM-III-R criteria) were
      compared with screened female controls (n = 124) and subsequently with male
      patients (n = 86). Two outcomes were investigated: (i) the proportion of subjects
      with one or more children (an index of fertility) and (ii) the number of children
      per subject among those with one or more children (an index of fecundity).
      Multivariate analysis was used to control for confounding variables. No
      significant differences in fertility between female patients and controls were
      detected, but reduced fecundity was noted among female patients past the
      reproductive period. Male patients showed a significant reduction in both
      fertility and fecundity compared to female patients. These results suggest that
      there is a relatively small impairment of fecundity among female patients
      compared with controls, but that there are more significant gender-related
      differences in both fertility and fecundity. The latter have important
      implications for the genetics of schizophrenia.

PMID- 9197900
TI  - The hypothalamic-pituitary-thyroid axis in major depression.
AB  - We investigated the capacity of several thyroid-axis measures to distinguish
      between depressed and control subjects and determined whether these variables
      were related to antidepressant treatment response. We studied 105 subjects who
      fulfilled the DSM-III-R criteria for a current major depressive episode and 41
      volunteers with no current mental disorder. The following thyroid-axis variables
      were measured: difference between T4 levels at 09.00 hours and 13.00 hours;
      baseline TSH; maximal TSH response to 400 micrograms TRH (delta max TSH); and
      presence of a blunted delta max TSH. The T4 difference variable alone
      distinguished between depressed and control subjects. In multivariate analyses,
      T4 difference and delta max TSH were independently related to antidepressant
      treatment outcome, and predicted a modest proportion (14%) of the variance in
      outcome. The relationship between these two variables and treatment outcome was
      particularly strong in depressed male subjects who were receiving desipramine,
      for whom they accounted for 36% of the variance in treatment outcome. The T4
      difference variable both distinguished between depressed and control subjects and
      was related to treatment outcome. Although this finding requires replication, it
      is consistent with other reports of the usefulness of thyroid-axis indices
      measured at different times of day in depressed patients.

PMID- 9197901
TI  - Sensitivity of the six-item Hamilton Depression Rating Scale.
AB  - We studied the sensitivity in detecting changes of the 6-item version of the
      original 17-item Hamilton Depression Rating Scale (HAM-D) and compared it with
      the more widely used versions among 164 depressed outpatients with and without
      atypical features before and after treatment with fluoxetine. The 6-item HAM-D
      was shown to be as sensitive as the 17-, 21- and 24-item versions of this scale.
      In addition, the different versions of the HAM-D were strongly correlated with
      each other at baseline and at the endpoint. It appears that the 6-item version of
      the HAM-D allows the assessment of severity of depression with comparable
      sensitivity to the standard and more elaborate versions of the same scale.

PMID- 9197902
TI  - Alexithymia in anorexia nervosa: a controlled study using the 20-item Toronto
      Alexithymia Scale.
AB  - The 20-item Toronto Alexithymia Scale (TAS) was completed at the age of 22 years
      by individuals who had previously suffered from anorexia nervosa (AN), and also
      by members of a comparison group. The AN and comparison groups had been recruited
      from community samples. Overall, the TAS scores did not clearly discriminate
      between the two groups. However, the AN group was significantly more often
      represented among subjects with the highest TAS scores. A subgroup with empathy
      disorder tended to have particularly high scores. It is concluded that
      alexithymia, as defined using the TAS-20, is found only in a subgroup of
      individuals with AN, and possibly more often in those who are also clinically
      diagnosed as suffering from empathy disorder. The TAS-20 is not suitable for
      screening of AN in the general population.

PMID- 9197903
TI  - Parapartum mental illness: an interview follow-up study.
AB  - A total of 54 parapartum mentally ill mothers and 89 controls were followed up
      approximately 6 years after childbirth. In total, 80% of the patients avoided
      further pregnancies during the follow-up period, compared to 58% of the controls
      (non-significant difference). One-third of the patients did not live together
      with their child, compared to only 3% of the controls. Index mothers tended to
      report more problematic relationships with their children. Poor childhood
      relationships during the mother's own childhood seem to be of special
      significance for the development of these problems. This study suggests a rather
      gloomy prognosis for parapartum mental illness. The suicide rate was 4.5%. In
      total, 22% of the patients, compared to none of the controls, had been on sick
      leave during the last 3 years, or had received a disability pension owing to
      mental illness at the time of the follow-up. The readmission rate for psychiatric
      in-patient care was 46% in the patient group.

PMID- 9197905
TI  - Generalized anxiety disorder in chronic fatigue syndrome.
AB  - A structured psychiatric interview, forming part of a global psychopathological
      approach, revealed higher prevalence rates of current and lifetime psychiatric
      disorders and a higher degree of psychiatric comorbidity in patients with chronic
      fatigue syndrome (CFS) than in a medical control group. In contrast to previous
      studies, a very high prevalence of generalized anxiety disorder (GAD) was found
      in CFS, characterized by an early onset and a high rate of psychiatric
      comorbidity. It is postulated that GAD represents a susceptibility factor for the
      development of CFS. A significantly higher prevalence was also observed for the
      somatization disorder (SD) in the CFS group. Apart from a higher female-to-male
      ratio in fibromyalgia, no marked differences were observed in sociodemographic or
      illness-related features, or in psychiatric morbidity, between CFS patients with
      and without fibromyalgia. CFS patients with SD have a longer illness duration and
      a higher rate of psychiatric comorbidity. These findings are consistent with the
      suggestion of Hickie et al. (1) that chronic fatigued subjects with SD should be
      distinguished from subjects with CFS.

PMID- 9197904
TI  - Early self-experienced neuropsychological deficits and subsequent schizophrenic
      diseases: an 8-year average follow-up prospective study.
AB  - The aim of the present study was to investigate the potential predictive value of
      early self-experienced neuropsychological deficits for the subsequent development
      of schizophrenia. A total of 96 patients with DSM-III-R diagnoses of personality
      disorders (formerly called 'neurotic disorders') who had been examined for the
      presence of such subjective experiences of deficits with standardized instruments
      were re-examined for the possible development of schizophrenic symptoms. After an
      average follow-up period of about 8 years, more than 50% of the patients had
      developed schizophrenia according to DSM-III-R criteria. In 77% of cases the
      outcome 'schizophrenia vs. no schizophrenia' was correctly predicted by the
      earlier presence or absence of self-experienced disturbances of thought, speech,
      memory, perception and action. These findings suggest that certain self
      experienced neuropsychological deficits are able to indicate susceptibility to
      psychosis.

PMID- 9197906
TI  - Schizophrenia and neurotrophin-3 alleles.
AB  - Studies of brain anatomy and premorbid functioning indicate that schizophrenia
      may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3
      (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located
      in the promoter region was found to be associated with schizophrenia in a
      Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association
      with schizophrenic patients with a putative neurodevelopmental form of the
      disease. We examined Swedish schizophrenic patients (n = 109) and control
      subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent
      exonic polymorphism (at Pro55). No significant difference was found between the
      two groups. However, in a meta-analysis including the present and previous
      studies of Caucasian subjects, the A3/147-bp allele frequency was found to be
      significantly higher in the schizophrenic patients. In the present study,
      carriers of the A3/147 bp allele tended to have an earlier age of onset and to
      display more extrapyramidal symptoms. In the silent exonic polymorphism (at
      Pro55), female schizophrenic patients had higher adenine and lower guanine allele
      frequencies than control female subjects. Together with previous studies, the
      results provide some support for an association between the NT-3 gene and certain
      forms of schizophrenia. This warrants further investigation of NT-3 and other
      neurotrophic factors with additional polymorphisms and larger patient samples.

PMID- 9197907
TI  - Temperament and personality features in panic disorder with or without comorbid
      mood disorders.
AB  - Personality and temperament features, assessed with the Structured Interview for
      DSM-III-R Personality Disorders-Revised (SIDP-R) and the Tridimensional
      Personality Questionnaire (TPQ), respectively, were evaluated in 62 patients
      affected by panic disorder with (PD + MD) (n = 22) or without comorbid mood
      disorder (PD) (n = 40). A significant difference in the prevalence of personality
      disorders (PD + MD, 86% vs. PD, 62%; P < 0.05), particularly dependent (PD + DM,
      50% vs. PD, 17%; P < 0.01) and borderline (PD + DM, 9% vs. PD, 0%; P = 0.05)
      personality disorders, was observed between the groups. Moreover, patients in the
      PD + MD group had higher scores for harm avoidance (PD + MD, 22.2 +/- 5.6 vs. PD,
      26.9 +/- 5.1; P < 0.05) than patients in the PD group. The harm avoidance score
      in PD patients was significantly related to personality disorder and not to MD,
      suggesting that harm avoidance is not associated with greater severity of the
      illness. Our data confirm the hypothesis that subjects with higher harm avoidance
      scores have a greater probability of being affected by cluster C personality
      disorders and comorbid mood and anxiety disorders.

PMID- 9197908
TI  - Phototherapy is a useful adjunct in the treatment of depressed in-patients.
AB  - Phototherapy is regularly used in the treatment of seasonal affective disorder.
      There is evidence that it is also useful in the treatment of non-seasonal
      depression, but relevant controlled experiments are difficult to design. In this
      study we randomly assigned depressed in-patients to high and low levels of
      artificial light, the high levels exceeding those most commonly used in earlier
      reported trials. Both unipolar and bipolar depressions responded when
      phototherapy was used as an adjunct to pharmacotherapy, and mood improvement was
      related to the intensity of illumination, that is, patients treated with high
      levels of illumination improved significantly more than those who received low
      levels (P < 0.02). Our findings suggest that light therapy is generally
      applicable to depressive illnesses, and that the light intensities commonly used
      are suboptimal.

PMID- 9197909
TI  - The prevalence of early postpartum psychiatric morbidity in Dubai: a
      transcultural perspective.
AB  - There have been numerous studies of the prevalence of postpartum psychiatric
      illness and its putative risk factors in Western Europe and North America, but
      very few studies have been undertaken in developing countries, including the Arab
      world. A total of 95 women admitted to the New Dubai Hospital in Dubai, United
      Arab Emirates, for childbirth were studied. All subjects were assessed in the
      postpartum period using clinical and socio-cultural instruments, namely the Self
      Reporting Questionnaire (SRQ) on day 2 and the Edinburgh Postnatal Depression
      Scale (EPDS) on day 7 after delivery. The prevalence of psychiatric morbidity was
      24% according to the SRQ and 18% according to the EPDS. A number of psychosocial
      factors emerged as putative risk factors for postpartum psychiatric disturbance,
      including depressive illness. It is concluded that the prevalence of postpartum
      psychiatric morbidity and its risk factors in this Arab culture are similar to
      the results obtained in numerous previous studies conducted in industrialized
      countries. These findings have implications for the early detection and care of
      women at risk for postpartum psychiatric illness.

PMID- 9197910
TI  - Attribution in somatizers: stability and relationship to outcome at 1-year follow
      up. Grupo Morbilidad Psiquica y Psicosomatica de Zaragoza (GMPPZ).
AB  - The aim of this study was to determine whether attributional style is a stable
      pattern in somatizers, to analyse the sociodemographic and psychopathological
      characteristics that can modify it, and to study the relationship between
      attributional pattern and outcome. A total of 147 somatizers and 46
      psychologizers from a representative sample (n = 1559) of primary care patients
      in Zaragoza, Spain were followed up for 1 year. Attribution of somatic symptoms
      was a stable construct in somatizers. Patients who modified attribution were
      younger (by 15 years on average), tended to be without a partner, and had a
      shorter illness duration (by 20 months on average) than those who maintained it.
      Attribution showed no correlation with outcome at the 1-year follow-up.

PMID- 9197911
TI  - Observations on switching patients with schizophrenia to risperidone treatment.
      Risperidone Switching Study Group.
AB  - This study examined one possible strategy for switching patients to treatment
      with risperidone involving immediate cessation of current neuroleptics and
      gradual withdrawal of anticholinergic treatments. All patients received
      risperidone monotherapy for at least 4 weeks. Side-effects and symptoms were
      rated and successful switching was defined as completion of the study with no
      consistent worsening in any rating scales. Of the 41 patients entered, five
      withdrew for reasons unconnected with the study. Of the remaining 36 patients,
      64% (23 patients) were switched successfully. Overall, the rating scales showed
      significant improvements (mean score on Krawiecka scale, 11.0 to 6.6, P < 0.001),
      and side-effects decreased (mean score on Simpson & Angus scale, 5.1 to 2.9, P =
      0.004). The strategy appeared to be successful for most patients, especially
      those who had previously received depot medication. However, more gradual
      withdrawal of previous treatments, including anticholinergics, may be advisable
      in some cases.

PMID- 9197912
TI  - Paroxetine efficacy in the treatment of generalized anxiety disorder.
AB  - Recently, there has been a renewed interest in alternatives to the
      benzodiazepines for the treatment of generalized anxiety disorder (GAD). The aim
      of the present study was to compare the efficacy of paroxetine vs. imipramine and
      2'-chlordesmethyldiazepam in 81 patients with a DSM-IV diagnosis of GAD.
      Approximately two-thirds of the patients who completed the study improved greatly
      or moderately on all three active drugs. During the first 2 weeks of treatment,
      2'-chlordesmethyldiazepam treatment resulted in the greatest improvement in
      anxiety ratings. Both paroxetine and imipramine treatment resulted in more
      improvement than 2'-chlordesmethyldiazepam by the fourth week of treatment.
      Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'
      chlordesmethyldiazepam affects predominantly somatic symptoms. Our results
      suggest that paroxetine is effective for the treatment of GAD.

PMID- 9197913
TI  - Personality disorder diagnoses using DSM-III-R in a Japanese clinical sample with
      major depression.
AB  - To investigate the availability of DSM-III-R Axis-II diagnoses in Japan, DSM-III
      R personality disorders (PDs) were diagnosed in a large sample of Japanese out
      patients with major depression. The SCID-II was administered to 118 consecutive
      out-patients with major depression. In general, the frequency of PD according to
      DSM-III-R criteria in this study was within the range of frequencies reported in
      North American and European studies. However, schizoid and narcissistic PDs were
      more frequent in this study. DSM-III-R diagnoses of PD would also be potentially
      useful for assessing personality disturbance in Japan. The DSM-III-R criteria for
      schizoid and narcissistic PDs may not be suitable for Japanese samples.

PMID- 9197914
TI  - Expressed emotion from the five-minute speech sample and relapse of out-patients
      with schizophrenia.
AB  - We investigated the relationship between 9-month relapse of 40 outpatients with
      schizophrenia and expressed emotion (EE) evaluated by the Five-Minute Speech
      Sample (FMSS). The results of this study suggest that the FMSS is suitable for
      use as a convenient instrument to measure EE, although it shows more false
      positive results. Therefore borderline EE of the FMSS might have to be regarded
      as high EE.

PMID- 9197915
TI  - Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human
      semen: a possible therapeutic modality for male factor infertility?
AB  - A new approach to reduce the level of reactive oxygen species (ROS) in human
      semen by using N-acetyl-L-cysteine (NAC) was evaluated. Semen samples were
      incubated with or without NAC (1.0 mg ml-1) at room temperature. The
      chemiluminescent signal of the oxidation of luminol was detected by means of an
      MTP reader after 0, 20, 40, 60 and 120 min, respectively, using 200 microM
      luminol. In addition, the dose-dependent action of NAC (0.1, 1.0 and 5.0 mg ml-1)
      and the influence of NAC on functional sperm parameters (motility and acrosome
      reaction) were studied. ROS levels decreased significantly after 20 min
      incubation with NAC. This reduction was greater in the high ROS group (> 30000
      counts/10(7) viable sperm at t = 0) than in the low ROS group (< 30000). In
      addition, a marked dose-dependence of NAC was observed. Concerning sperm
      function, total sperm motility improved after incubation with NAC, but no
      significant change was observed with respect to the acrosome reaction. NAC (at
      concentrations of 1.0 mg ml-1) significantly reduced ROS in human semen and
      showed the possibility of improving impaired sperm function. After further
      testing NAC might be useful for the treatment of male infertility patients.

PMID- 9197916
TI  - Comparison of two staining and evaluation methods used for computerized human
      sperm morphology evaluations.
AB  - The purpose of the study was to analyse the agreement between computer analysed
      (Hamilton Thorne, IVOS Dimensions Version 3) normal sperm morphology and values
      obtained from 97 slides stained according to the Papanicolaou and Diff-Quik
      method. Liquefied semen samples were washed once by centrifugation and air dried
      smears on slides were made, which were stained according to the Papanicolaou and
      Diff-Quik method and analysed by computer. The paired t-test was used to assess
      whether any bias existed between the two methods. The limits of agreement were
      calculated using the Bland and Altman approach and a modification of this
      approach (mean-dependent limits). A significant bias of 1.6% was obtained in
      favour of higher normal sperm morphology percentages when using the Diff-Quik
      method. The standard limits of agreement were -13.4% to 16.6%, whereas the mean
      dependent limits of agreement were 1.6% [5.8 + 0.6 (mean percentage normal
      morphology)]. Statistically, the Diff-Quik and Papanicolaou staining methods
      produce different normal sperm morphology profiles. These inherent differences
      may, therefore, require the establishment of new normal sperm morphology
      thresholds for male fertility, based on clinical data, when using the Diff-Quik
      staining method in conjunction with computerized analysis.

PMID- 9197917
TI  - Serum lactate dehydrogenase isoenzyme 1 as predictor of tumor-associated death in
      patients with testicular germ cell tumours.
AB  - Serum lactate dehydrogenase iso-enzyme 1 (S-LD-1) was determined in 24 patients
      with testicular germ cell tumours who died during follow-up. Serum samples were
      obtained at the start of chemotherapy or late into the clinical course for those
      without evidence of a tumour. Seven of the eight patients with tumour-associated
      death had S-LD-1 > 150 U l-1 (median 260 U l-1 range 90-905 U l-1, as did two of
      the six who died without evidence of a tumour (median 134 U l-1 range 89-128 U l
      1) (P = 0.03, Mann-Whitney U-test, two-tailed). The remaining 10 patients had
      previously been reported as to prediction of S-LD-1 for the prognosis, and were
      evaluated only as to the reproducibility of the S-LD-1 determination. S-LD-1 was
      determined in two serum samples obtained concomitantly from eight of these 10
      patients: the difference between the two S-LD-1 determinations was median 6% of
      the average of the two S-LD-1 determinations (25-75% range 3-17%). Our study
      showed an unforeseeable high level of imprecision of the assay system.
      Nevertheless, S-LD-1 determinations in the regular monitoring of patients with
      testicular germ cell tumours may be useful for predicting tumour-associated
      deaths.

PMID- 9197918
TI  - Effects of erythropoietin, bromocryptine and hydralazine on testicular function
      in rats with chronic renal failure.
AB  - We evaluated the effects of chronic renal failure (CRF) on testicular function
      and semen physiology. A CRF model was created in 48 male rats by performance of
      five-sixths nephrectomies in two-stage procedures, and a control (group A) by two
      stage sham operation on six male rats. Seven weeks later, serum urea and
      creatinine concentrations were assessed, and the nephrectomized rats were then
      equally divided into four groups, B, C, D and E, and treated with saline,
      erythropoietin, bromocryptine and hydralazine, respectively. Seventeen weeks
      after the first surgical procedure, the number of fertile rats, the mean values
      of epididymal sperm content and motility, the outcome of in vitro fertilization,
      and peripheral serum testosterone concentrations and responses to human chorionic
      gonadotropin were significantly higher (P < 0.05) in groups A, C and D than in
      groups B and E. Serum prolactin concentration was significantly higher (P < 0.05)
      in all groups of nephrectomized rats than in group A. Our results indicate that
      bromocryptine and erythropoetin improve Leydig cell function, spermatogenesis
      epididymal sperm maturation, and sperm fertilizing capacity in rats with CRF.

PMID- 9197919
TI  - Sperm binding and ultrasound changes after operative repair of varicocele:
      correlation with fecundity.
AB  - The study was conducted to evaluate the changes in sperm binding capacity and
      ultrasound measurements of the internal spermatic vein, after operative repair of
      a varicocele. In order to clarify the effect of a varicocele on fertility, these
      changes were correlated to pregnancy achievement. Twelve infertile males with
      subnormal semen parameters and varicocele, underwent operative repair. Pre- and
      post-operatively, all had semen analysis, hemizona assay and ultrasound of the
      internal spermatic veins. The patients were divided into three subgroups
      according to pregnancy outcome, and the changes in the different evaluation tests
      after the operation were compared. Sperm concentration and motility improved post
      operatively in all three subgroups, whereas the hemizona index and
      ultrasonographic measurements improved significantly only in the subgroup that
      achieved early pregnancies (the mean post-operative percentage of normal
      morphology was significantly higher), compared to the subgroup without
      pregnancies. Unlike sperm parameters which improve after operative repair of the
      varicocele, but have no correlation to conception, sperm binding and ultrasound
      measurements of the internal spermatic veins improve significantly in cases that
      achieve early pregnancies. The use of these tests, as well as measuring the
      percentage of normal morphology, are recommended in all cases of infertility
      related varicocele.

PMID- 9197920
TI  - A quantitative morphological study of age-related changes in the donkey testis in
      the period between puberty and senium.
AB  - The testis of the donkey was used as a model to study age-related changes in the
      period between puberty and senium. From the age of 1.5 years to the middle of
      sexual maturity (5 to 6 years) a number of histophysiological features, all
      indicative of the spermatogenetic efficiency, increase continuously. Then without
      a longer-lasting plateau of maximal performance these features undergo continuous
      retrogression. Thus, the adult testis is an organ in permanent change. During its
      progressive period (1.5 to 5 years) the average testicular and tubular volumes
      treble. The increase in tubular volume is due to an increase in tubular length
      (from 700 m to 1600 m per testis) and tubular diameter (from 205 microns to 250
      microns). Parallel to this growth, the spermatogenetic efficiency of the
      seminiferous epithelium rises: the number of germ cells entering meiosis
      increases and the cell loss by apoptosis or exfoliation decreases. During the
      following regressive period of the testis (5-10 years) seminiferous epithelial
      height and tubular diameter are again gradually reduced to 70 microns and 205
      microns, respectively. The absolute number of Sertoli cells per testis decreases
      continuously from puberty onwards. The tubular lamina propria thickens with
      advancing age and at the age of 10 years, displays long irregular projections
      into the seminiferous epithelium.

PMID- 9197921
TI  - Flow cytometric determination of binding of monoclonal antibodies to human
      spermatozoa.
AB  - Although several monoclonal antibodies to sperm antigens are available, only few
      systematical reports on the appearance of distinct antibody binding structures in
      spermatozoa of infertile patients are available. We studied the binding frequency
      of six monoclonal antibodies (TUS-1, -2, -10, -17, -19, -20) by means of a flow
      cytometer in different semen samples and their possible relationship to other
      sperm parameters, in particular to the motility parameters as determined by
      computer-assisted semen analysis. The percentage of vital spermatozoa binding the
      different antibodies was 21.5% (TUS-2) to 52.1% (TUS-20). The percentage binding
      was higher in samples with normozoospermia than in those with oligo
      asthenoteratozoospermia. A significant correlation occurred between sperm
      concentration and the percentage of spermatozoa stained by TUS-2 and TUS-17;
      between motile spermatozoa and those binding TUS-17 and TUS-20; the velocity
      average path and those binding TUS-17; an inverse correlation occurred between
      the morphologically-abnormal spermatozoa and those binding TUS-20; an inverse
      correlation between TUS-17 and acrosin. We conclude from our results that
      although the antigens of the antibodies concerned are not yet characterized, the
      determination of antibody binding will give additional information on the
      functional status during capacitation and acrosome reaction of spermatozoa.

PMID- 9197922
TI  - Effects of manganese salts on the AIDS-related pathogen, Cryptosporidium parvum
      in vitro and in vivo.
AB  - The authors examined the effects of manganese salts on the interaction of the
      AIDS-related pathogen, Cryptosporidium parvum, with human ileoadenocarcinoma (HCT
      8) cells in vitro. Manganese (Mn) inhibited binding of C. parvum sporozoite
      membrane antigens to intact, fixed HCT-8 cells in a dose-dependent fashion,
      whereas Ca++, Mg++, and Zn++ salts had no effect. Manganese was also found to
      affect sporozoite penetration of live HCT-8 cells, which resulted in a dose
      dependent inhibition of parasite development. However, the levels of Mn++ needed
      in the live cell assays was approx 10-fold greater than in the fixed-cell assays.
      This inhibition of parasite development was not reversible when Ca++ or Mg++ were
      used as competitors. Oral supplementation of suckling mice infected with C.
      parvum with MnSO4 resulted in significant reductions and, in some cases,
      elimination of intestinally derived oocysts.

PMID- 9197923
TI  - Human fetal endothelial cells acquire zinc(II) from both the protein bound and
      nonprotein bound pools in serum.
AB  - To help determine physiologically important routes by which zinc (Zn) is acquired
      by human fetal vascular endothelium, the authors incubated cultured umbilical
      vein endothelial cells with 65Zn(II)-tracer labeled human fetal whole serum,
      ultrafiltrate (containing low molecular mass serum zinc complexes), and dialyzed
      serum (containing protein-bound zinc). Zinc from whole serum and from both serum
      fractions entered a rapidly labeled cellular compartment, removable by edetic
      acid (EDTA), representing Zn bound to the outside cell surface, and
      accumulatively, an EDTA-resistant compartment-probably largely internalized Zn.
      Entry of Zn into the EDTA-resistant pool from both serum fractions was strongly
      temperature-dependent, and was not via the EDTA-sensitive pool. Entry from the
      ultrafiltrate was resolvable into high affinity saturable, and non- (or hardly-)
      saturable components. Transfer from the dialyzed serum fraction was not
      significantly saturable, but only partially accounted for by nonspecific
      pinocytosis. Thus, Zn is obtained by fetal vascular endothelium partly from low
      molecular mass serum species, probably through at least one carrier-mediated
      membrane transport system; but also from Zn complexed with serum protein, via at
      least one metabolism-related route.

PMID- 9197924
TI  - The effect of boron supplementation on its urinary excretion and selected
      cardiovascular risk factors in healthy male subjects.
AB  - Boron (B) is an essential trace element for plants and its interrelationship with
      mineral and bone metabolism and endocrine function in humans has been proposed.
      Relatively little is known about the occurrence of B in the food chain and hence
      a biomarker which reflects its intake is required. Two studies were carried out
      to quantify the urinary B concentration of subjects consuming their habitual diet
      and the effect of supplementation. In addition, the effect of supplementation on
      plasma lipoprotein cholesterol concentrations and susceptibility to oxidation and
      plasma steroid hormones were determined. Boron excretion, obtained on two
      different occasions from 18 healthy male subjects, was found to be in the range
      0.35-3.53 mg/day, with no significant difference between the two occasions.
      Supplementation with 10 mg B/d for 4 wk resulted in 84% of the supplemented dose
      being recovered in the urine. Plasma estradiol concentrations increased
      significantly as a result of supplementation (51.9 +/- 21.4 to 73.9 +/- 22.2
      pmol/L; p < 0.004) and there was a trend for plasma testosterone levels to be
      increased. However, there was no difference in plasma lipids or the oxidizability
      of low-density lipoprotein. Our studies suggest that the absorption efficiency of
      B is very high and estimation of the urinary B concentration may provide a useful
      reflection of B intake. In addition, the elevation of endogenous estrogen as a
      result of supplementation suggests a protective role for B in atherosclerosis.

PMID- 9197925
TI  - Effects of boron on growing pullets.
AB  - The effect of dietary boron on bone ash content and on the ultimate shear force,
      stress, and fracture energy of the tibia, femur, humerus, and radius from white
      Leghorn pullets were investigated. There was a significant increase in the shear
      force of the tibia and femur for pullets supplemented with 50 and 100 mg/kg of
      dietary boron. There was a significant increase in the shear stress of the tibia
      at 50 and 100 mg/kg of boron, and also an increase in shear fracture energy at 50
      and 100 mg/kg boron for the femur. Tibia bone ash content increased significantly
      at 50, 100, and 200 mg/kg boron with the highest value at 50 mg/kg. Even though
      there was not a significant increase in body wt at 50 and 100 mg/kg boron, the
      pullets fed these supplements were consistently heavier than the control group.

PMID- 9197926
TI  - Enhancement of adriamycin toxicity by iron chelates is not a free radical
      mechanism.
AB  - The possible involvement of metal ions and free radicals in the cytotoxic
      mechanism of Adriamycin (ADR) was investigated, using a model system of
      Escherichia coli cells. It is shown that E. coli mediated the production of free
      radicals under anaerobic (ADR-semiquinone) and aerobic (superoxide) conditions.
      ADR-induced loss of colony-forming ability was enhanced by the addition of iron
      (Fe) chelates. These observations suggested that a Fenton-type free radical
      mechanism was responsible for ADR toxicity. However, the mortality rate was
      essentially unchanged by the exclusion of oxygen. It was also unaffected by the
      addition of H2O2, catalase, or chelating agents. Cu(II), Zn(II) or Mg(II) had no
      effect on ADR toxicity. ADR and iron chelates did not induce measurable amounts
      of DNA strand-breaks. These observations suggest a mechanism of ADR-induced cell
      killing that is enhanced by Fe chelates, but does not directly involve oxygen
      derived free radicals.

PMID- 9197927
TI  - Changes in iron, calcium, magnesium, copper, and zinc levels in different tissues
      of riboflavin-deficient rats.
AB  - To clarify the changes of mineral levels in different tissues of riboflavin
      deficient rats, Wistar rats were separated into three groups. One group was fed a
      diet ad libitum that was deficient in riboflavin. The other two were fed either
      the complete diet that was weight-matched to the riboflavin-deficient group or
      fed a complete diet ad libitum. In riboflavin-deficient rats, the hemoglobin
      concentration and riboflavin contents of blood, liver, and kidney were
      significantly decreased, compared with weight-matched and ad libitum-fed
      controls. The mineral concentrations of tissues are summarized as follows: The
      iron (Fe) concentration in the heart, liver, and spleen was decreased in the
      riboflavin-deficient group compared with the other groups. Calcium (Ca) and
      magnesium (Mg) concentrations in tibia were decreased in the riboflavin-deficient
      group compared with the other two groups. Copper (Cu) concentration was increased
      in the heart and liver, when the riboflavin-deficient group was compared with the
      other groups. Zinc (Zn) concentration was increased in tibia when the riboflavin
      deficient group was compared with the other groups.

PMID- 9197928
TI  - Determination of cadmium and lead levels in human blood of a general Czech
      population by GFAAS.
AB  - The development of a method for the direct determination of cadmium (Cd) and lead
      (Pb) in blood samples by GFAAS, is described. Samples were properly diluted by a
      matrix modifier to enable measuring both analytes in one solution. For the
      determination of Cd, a matrix-matched, and for the determination of Pb, an
      aqueous calibration was used. The precision, accuracy, and detection limits of
      this method are presented. A method is applied to the investigation, of Cd and Pb
      levels in a general Czech population, selected according to the WHO-MONICA
      project criteria. To avoid possible contaminations, samples were treated in a
      clean room class 100.

PMID- 9197929
TI  - The protective role of selenium on the toxicity of cisplatin-contained
      chemotherapy regimen in cancer patients.
AB  - The effect of selenium (Se) in reducing the toxicity of cisplatin in cancer
      patients was studied. Forty-one patients were randomized into group A (20
      patients with Se administration in first cycle of chemotherapy as study cases and
      without Se in second cycle of chemotherapy as control) and group B (21 patients
      without Se in first cycle of chemotherapy and with Se in second cycle of
      chemotherapy). The 4000 micrograms per day of Se as Seleno-Kappacarrageenan were
      administered from 4 before to 4 d after chemotherapy for study cases. The serum
      Se increased from 70.4 +/- 22.86 to 157.04 +/- 60.23 ng/mL (P < 0.001) in
      patients received Se. The cisplatin dosage was iv administration in 60-80 mg/m2
      on the first day. The results showed that the peripheral WBC counts on day 14
      after initiation of chemotherapy in study cases was significantly higher than the
      controls (3.35 +/- 2.01 vs 2.31 +/- 1.38 [x10(9)L])/L, p < 0.05). On the other
      hand, the consumption of GCSF for the cases was significantly less than the
      controls (110.1 +/- 82.2 vs 723.6 +/- 192.6 IU, p < 0.05). The volumes of blood
      transfusion for the study group were also significantly less than the controls (0
      vs 62 +/- 38 mL, p < 0.05). The nephrotoxicity of cisplatin was measured by urine
      enzymes (NAG, GGT, AAP, LAP, and ALP) were determined prior to and at 2, 24, 48,
      and 72 h after initiation of chemotherapy. The urine enzymes NAG, GGT, AAP, and
      ALP after chemotherapy for cases were significantly lower than the controls. No
      toxicity of Seleno-Kappacarrageenan was noted. The above results suggest that the
      Se can be used as an agent for reducing the nephrotoxicity and bone marrow
      suppression induced by cisplatin.

PMID- 9197930
TI  - Five-year incidence of coronal and root caries in 60-, 70- and 80-year-old
      Swedish individuals.
AB  - The 5-year incidence of caries was studied in a random sample of 60-, 70- and 80
      year-old inhabitants of Goteborg, with 69, 51 and 28 individuals in the different
      age groups. One aim of the study was to introduce a root caries index (DMFRS%) in
      which the missing root surfaces are taken into account. This study, as well as
      other recent studies, has shown that dental caries is the main reason for tooth
      extraction. The study also revealed that coronal and root caries occurred more
      frequently in elderly than younger people and the incidence of root caries was
      positively correlated with coronal caries (r = 0.3, p < 0.001) and negatively
      correlated with the number of remaining teeth (r = 0.4, p < 0.0001). The 5-year
      DMFRS% increment values increased with advancing age from 2.7 involved root
      surfaces per 100 susceptible ones in the 60-year-olds to 4.8 in the 70-year-olds
      and 10.7 in the 80-year-olds. It should be mentioned, however, that only people
      able to come to the clinic were enrolled in the study and an analysis of the
      attrition bias indicated that oral health may be worse in those who are too ill
      to participate. The frequent utilization of dental care among the participants
      was reflected in the finding of several new fillings and prosthetic crowns. Most
      of the very elderly people with carious lesions at baseline, however, had
      developed new lesions at the margins of the newly made restorations.

PMID- 9197931
TI  - Effects of fluoride level in drinking water, nutritional status, and socio
      economic status on the prevalence of developmental defects of dental enamel in
      permanent teeth in Saudi 14-year-old boys.
AB  - Fourteen-year-old boys from three regions of Saudi Arabia were surveyed in
      1992/3. These regions were Jeddah (which receives desalinated water containing
      0.22 mgF/l), Riyadh (receiving water containing 0.78 mgF/l) and Qassim (2.66
      mgF/l). For each of these urban communities an adjacent rural community was
      selected; these received water with 0.25, 0.80, and 2.71 mg/l, respectively.
      Subjects from the urban communities were classified into high, medium and low
      socio-economic status based on area of residence, income and education level of
      parents. Nutritional status was calculated from height and age using WHO methods
      and expressed as height for age percentage of the median of the reference
      population (HAM); children with HAM scores of less than 95% were classed as
      malnourished. The developmental defects of enamel index was recorded on the
      buccal surface of all permanent teeth, by one examiner. Colour photographs of
      anterior teeth were read 'blind' to investigate examiner bias between regions
      there was no bias. A total of 1,539 children were examined who had been
      continuously resident in that community. Overall, 83% of subjects had one or more
      enamel defects with a mean number of teeth affected per person of 9.6. Diffuse
      defects were the most common. Multivariate analyses revealed that all three
      variables-region, nutritional status, socio-economic status-were statistically
      significantly related to the prevalence of defects and the number of teeth
      affected: prevalence was highest in the region with the highest water fluoride
      concentration, in rural areas and in malnourished subjects. Maxillary incisor
      teeth were the most affected teeth in all regions. The findings have implications
      for those in public health who determine optimum fluoride levels in drinking
      water in Saudi Arabia and beyond.

PMID- 9197932
TI  - Passive immunization against dental plaque formation in humans: effect of a mouth
      rinse containing egg yolk antibodies (IgY) specific to Streptococcus mutans.
AB  - Passive immunization involving the delivery of antibodies specific to pathogens
      of infectious diseases to the host has been an attractive approach to establish
      protective immunity against a variety of microbial pathogens, including
      Streptococcus mutans, which is the principal etiologic agent of dental caries in
      humans. The overall purpose of the present study was to determine the
      effectiveness of a mouth rinse containing antibodies to S. mutans in preventing
      the establishment of this bacterium in dental plaque of humans. The antibodies
      were derived from egg yolks obtained from hens immunized with whole cells of S.
      mutans grown in sucrose-containing medium. The immunoglobulin derived from the
      yolks (IgY) of immunized hens was characterized in vitro and in vivo in human
      volunteers. Cross-reactivity tests showed that immune IgY reacted with every
      serotype, except serotype b, which had lost its GTase activity, when the bacteria
      were cultured in sucrose-containing medium. Immune IgY inhibited S. mutans
      adherence to saliva-coated hydroxyapatite discs by 59.2%, while control IgY
      caused an inhibition of only 8.2%. In the short-term (4-hour) test using a mouth
      rinse containing 10% sucrose, immune IgY decreased the ratio of the percentage of
      S. mutans per total streptococci in saliva. In the long-term (7-day) test using a
      mouth rinse without sucrose, the ratio in saliva was not significantly reduced in
      the volunteers using the immune IgY due to the large standard deviation. However,
      comparing the ratios of the percentage of S. mutans per total streptococci in
      plaque of individual subjects, there was a tendency for a reduction of the ratios
      in the volunteers receiving the mouth rinse containing immune IgY. These results
      support the effectiveness of IgY with specificity to S. mutans grown in the
      presence of sucrose as an efficient method to control the colonization of mutans
      streptococci in the oral cavity of humans.

PMID- 9197933
TI  - Inhibitive effect of a resin-modified glass ionomer cement on remote enamel
      artificial caries.
AB  - Glass ionomer cements (GICs) demonstrate the inhibition of caries lesions formed
      immediately adjacent to the restoration. This in vitro study was conducted to
      evaluate the distance at which a resin-modified GIC is able to exert its
      cariostatic effect on artificial enamel lesions ('remote effect'). Resin-modified
      GIC or bis-GMA resin was applied on the cervical third of the labial surface of
      10 paired halves of bovine incisors. Specimens were separately immersed for 3
      weeks in lactic acid gel which was changed every other day to reduce fluoride
      accumulation. Artificial lesions were examined by the cross-sectional
      microhardness (MHN) method. Volume percent mineral, mineral loss (delta Z value)
      and change in mineral content (delta M) were computed for each MHN profile,
      performed at distances of 0.2, 0.5, 1.0, 2.0, 4.0 and 7.0 mm from the edge of the
      materials. delta Z values of the resin-modified GIC group were significantly
      lower than those of the bis-GMA control group at all remote sites (t test, p <
      0.05). The delta M caused by resin-modified GIC was more pronounced within 1.0 mm
      from the material which suggested that the demineralization inhibition can be
      divided into the near effect (< 1.0 mm). In this in vitro study, resin-modified
      GIC provided caries resistance in bovine enamel located at a considerable
      distance from the margin of the material.

PMID- 9197934
TI  - Metastasizing extraneural tumors along the CSF pathway.
AB  - Dissemination of metastases from primarily extraneural tumors with the
      cerebrospinal fluid (CSF) is rare and most often seen in association with a
      leptomeningeal involvement. Here we present 2 cases of bronchogenic and 1 case of
      prostata carcinoma with multiple CSF metastases within the entire cerebral
      ventricles and the spinal canal.

PMID- 9197935
TI  - Abnormal expression of cell adhesion molecule L1 in migration disorders: a
      developmental immunohistochemical study.
AB  - We studied immunohistochemically the expression pattern of a neural cell adhesion
      molecule, L1, in various human migration disorders associated with
      polymicrogyria: 4 fetuses and 11 infants having Fukuyama type congenital muscular
      dystrophy (FCMD) (4 cases), Zellweger syndrome (6) or thanatophoric dysplasia (3)
      and intrauterine brain damages (2) at different development stages, comparing to
      age-matched controls. There were different patterns of L1 expression, which
      suggested at least 3 pathogenetic mechanisms: high expression associated with
      neuoraxonal overgrowth (fetal FCMD and destructive event at intermigratory
      period); delayed expression with neuronal dysmaturation and dysmyelinogenesis
      (late infantile stage of Zellweger syndrome); no expression in toxic or
      destructive brain injury (Zellweger syndrome or destructive events at inter-or
      postmigratory periods).

PMID- 9197936
TI  - Primary melanocytomas of the spinal cord: a report of seven cases.
AB  - Seven cases of primary intramedullary melanocytomas of the spinal cord are
      reported with clinical features, light microscopy, immunohistochemistry, and
      ploidy analysis. The patients ranged in age from 24 to 74 years. The tumors were
      composed predominately of spindle cells with focal aggregates of epithelioid
      cells. The nuclei were round to oval with variably prominent nucleoli. The tumors
      contained variable amounts of melanin pigment. Immunohistochemical staining with
      HMB 45 was positive in 5 cases and negative in 2. None of the tumors was
      immunoreactive for epithelial membrane antigen (EMA). The clinical outcome ranged
      from death at 9 days following surgery to 4-year survival without recurrence. The
      tumors were compared with 5 metastatic melanomas and were found to have a
      markedly different histology, S phase fractions, and proliferation indices. The
      categorization of the primary pigmented lesions of the CNS is further discussed
      in the context of dermatopathologic nomenclature. These 7 tumors appear to be a
      type of primary central nervous system neoplasm which lacks markedly anaplastic
      features and exhibits locally aggressive behavior.

PMID- 9197937
TI  - Postmortem delay and temperature conditions affect the in situ end-labeling
      (ISEL) assay in brain tissue of mice.
AB  - Apoptotic cell changes occurring under certain developmental, physiological, and
      pathological conditions have been of increasing interest during recent years. Due
      to occasional difficulties in detecting apoptosis in routinely stained sections,
      various methods have been developed to facilitate tissue examination.
      Fragmentation of DNA during the process of apoptosis is a prerequisite for
      detection in the in situ end-labeling (ISEL) procedure. It is yet unclear whether
      other mechanisms of cell change that induce DNA fragmentation such as necrosis
      and postmortem autolysis also show positive staining with the ISEL technique. To
      investigate whether the ISEL assay visualizes autolytic DNA changes along with
      apoptotic DNA fragmentation, we tested the technique on brain tissue of mice
      after different time intervals (0, 6, 12, 24, 48, 72 h) of postmortem delay (PMD)
      and at 2 different temperatures of postmortem storage (4 degrees C and room
      temperature (RT)). Our semiquantitative results show that up to 24 h of PMD no
      prominent difference in labeling is observable at both temperatures. After 48 and
      72 h of PMD at RT clusters of labeled cells begin to appear. Clusters of stained
      cells should therefore not be considered as apoptosis when using the ISEL assay.

PMID- 9197938
TI  - Ki-67 immunoreactivity in meningiomas--determination of the proliferative
      potential of meningiomas using the monoclonal antibody Ki-67.
AB  - The proliferative potential of 66 human intracranial meningiomas (15 benign, 15
      atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated
      by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This
      antibody recognizes a nuclear antigen present in human cells during all active
      phases of the cell cycle, but absent in the resting phase. The purpose of this
      retrospective study was to estimate the Ki-67-labelling index (L.I.) and see if
      this index could help discriminate between the different groups of meningiomas.
      Our results demonstrated that L.I. could discriminate between benign, bone
      invasive/atypical, brain-invasive meningiomas. In the recurrent group of
      meningiomas the L.I. decreased from the first to the last operation. We conclude
      that estimation of L.I. at the time of the operation might help identify
      meningiomas with a high growth potential and thereby give valuable information
      concerning the prognosis.

PMID- 9197939
TI  - Primary Candida albicans empyema associated with epidural hematomas in
      craniocervical junction.
AB  - The case of a 27-year-old patient with chronic candida empyema in the
      craniocervical junction is presented. Occlusive hydrocephalus at admittance,
      primary subdural candida empyema, and recurrent epidural bleedings are the
      outstanding features in the clinical course. Despite intact immunity this patient
      acquired primary candidosis of CNS. Pathological changes in dura, ventricular
      system, and CSF required multiple shunt revisions. Antimycotic therapy was
      performed with a combination of 3 antimycotics. The clinical improvement was
      prolonged by several complications.

PMID- 9197940
TI  - A new clinical tool for gait evaluation in Parkinson's disease.
AB  - This study was devised to check the feasibility and validity of a rating scale
      specifically designed to evaluate gait impairment in Parkinson's disease (RSGE).
      Demographic data, a brief questionnaire on general aspects influencing gait and
      mobility, a battery of scales (Barthel Index; Hoehn and Yahr staging; and
      Northwestern University Disability, Schwab and England, and Unified Parkinson's
      Disease Rating Scale [UPDRS]), and timed tests ("Up and Go" and "Steps x Seconds"
      tests) were recorded under protocol, as was the RSGE-Version 1.0 (23 items in
      four subscales). Fifty patients enrolled at two centers were included. Twenty
      five (50%) were simultaneously (though independently) evaluated by three
      examiners, in order to determine the interrater reliability. The mean age of the
      patients was 67.6 +/- 11.16 years, with a mean 8.18 +/- 5.58 years of disease
      duration. Motor fluctuations were present in 48% of patients. The RSGE Cronbach's
      alpha was 0.94. Only the item "Dyskinesias" was not correlated with the RSGE
      total sum. The item "Axial rigidity" showed a fair interrater reliability (kappa
      = 0.30). However, most of the RSGE items (16/23, 70%) had kappa > or = 0.65. The
      convergent validity with the applied scales was very high (Spearman r = 0.74
      0.90, p < 0.001). The highest correlation (0.90) was obtained with the UPDRS.
      Also, the RSGE correlation with timed tests was very satisfactory ("Up and Go" =
      0.81; "Steps x Seconds" = 0.70; both, p < 0.001). Factor analysis of the RSGE
      disclosed four dimensions explaining 68% of the variance. The RSGE-Version 1.0
      proved to be a valid instrument. The reliability of some items has to be
      improved, however.

PMID- 9197941
TI  - Automatic EMG-guided botulinum toxin treatment of spasticity.
AB  - Conventional electromyographic (EMG) guidance in botulinum toxin therapy can
      localize a muscle, but the amount of electrical activity is assessed only
      subjectively. We wanted to introduce a quantitative EMG criterion, according to
      which the decision for/against toxin application could be made. Turn/amplitude
      analysis (TAA) was applied to nine patients with severe paraspasticity (n = 5),
      right upper or lower limb spasticity (n = 3), or tetraspasticity (n = 1) before
      and after toxin administration. Muscles were selected for toxin application if
      both mean turns/second and mean amplitude/turn exceeded the level of 150. A mean
      Dysport dose of 116 mouse units (mu) (range 40-240 mu) was administered to each
      of the 26 muscles that met the EMG criterion. Thirty days after the injection,
      activities of daily living, pain, and TAA count improved in 89%, tone in 78%, and
      range of motion in 56% of the patients by at least 1 point on corresponding 5
      point rating scales. TAA provides a useful EMG criterion for/against botulinum
      toxin application. Muscle selection according to this criterion leads to a
      significant subjective and objective toxin effect. TAA is a valuable tool to
      determine the benefit of single and subsequent botulinum toxin injections in the
      treatment of spasticity.

PMID- 9197942
TI  - Low dose of clozapine in the treatment of dopaminergic psychosis in Parkinson's
      disease.
AB  - Dopaminergic psychosis frequently complicates the pharmacological treatment of
      Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with
      conventional neuroleptics improves psychosis but worsens parkinsonism. In an open
      label 12-month trial, the clinical antipsychotic efficacy of the atypical
      neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46
      85 years) with symptoms of dopaminergic psychosis including delusions, vivid
      dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine,
      given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to
      the minimal effective dose. In all patients, psychosis responded to very low
      clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the
      severity of psychosis. During clozapine treatment, parkinsonian disabilities and
      levodopa dosage remained statistically unchanged. During the 12-month study, no
      patient had clozapine-induced agranulocytosis or other severe side effects. These
      findings indicate that even at low doses, clozapine effectively controls
      dopaminergic psychosis in Parkinson's disease patients without compromising motor
      function.

PMID- 9197943
TI  - Mianserin, a 5-HT2a/2c and alpha 2 antagonist, in the treatment of sexual
      dysfunction induced by serotonin reuptake inhibitors.
AB  - Sexual dysfunction is commonly encountered in patients treated with
      antidepressants. The exact mechanism responsible for the sexual impairment is as
      yet unclear, although activation of the serotonergic system has been implicated.
      In the present study, we examined the effect of the 5-HT2a/2c and alpha 2
      antagonist mianserin in the treatment of patients with sexual dysfunction induced
      by serotonin reuptake inhibitors (SRIs). Mianserin 15 mg was coadministered to 15
      male subjects with new-onset sexual dysfunction who were under treatment with
      SRIs. Four major domains of sexual activity-desire, erection, orgasm, and
      satisfaction-were assessed once weekly for 4 weeks. At the end of the study, 9 of
      the 15 subjects reported a marked improvement in their sexual functioning, 2
      reported partial improvement, and only 4 subjects showed no improvement at all.
      The beneficial effects were prominent in the areas of orgasm and satisfaction and
      were usually noted within the first and second week of mianserin treatment. The
      addition of mianserin to the treatment regimen was not associated with either
      improvement or worsening of the basic psychiatric clinical status. It appears
      that the coadministration of low-dose mianserin may be an additional option in
      the treatment of sexual dysfunction induced by SRIs.

PMID- 9197944
TI  - Significant inhibition of spontaneous IgA secretion by selective peripheral-type
      benzodiazepine receptor ligands.
AB  - The in vitro effect of benzodiazepine (BZ) receptor ligands on the secretion of
      immunoglobulin isotypes IgM, IgG, and IgA by human peripheral blood mononuclear
      cells (PBMCs) was examined. It was found that the specific peripheral-type BZ
      receptor (PBR) ligands (Ro5-4864 and PK 11195) inhibit the spontaneous secretion
      of IgA by human PBMCs in a dose-dependent manner, in the micromolar range. The
      decreased secretion of IgG and IgM induced by these ligands did not reach
      significant levels. The mixed BZ ligands (diazepam and flunitrazepam) had no
      consistent or significant effect on the production of the three immunoglobulin
      isotypes tested in the current study. The central-type ligand (clonazepam) did
      not affect IgM, IgG, or IgA secretion. The significant inhibitory effect of PBR
      ligands was confined to the spontaneous secretion of IgA by human PBMCs, and no
      such effect was detected in cells stimulated by pokeweed mitogen to produce
      immunoglobulins. It seems that PBR ligands are capable of suppressing spontaneous
      IgA secretion, but fail to affect the augmented production induced by mitogen.

PMID- 9197945
TI  - Antinociceptive effects of the kappa-opioid receptor agonist RP 60180 compared
      with pentazocine in an experimental human pain model.
AB  - Agonists at kappa-opioid receptors may preserve the analgesic properties of mu
      opioidergic agonists while avoiding their major adverse effects. The present
      study was aimed to investigate the antinociceptive effects of the new kappa
      opioid receptor agonist RP 60180. An experimental pain model was used based on
      specific pain stimuli and event-related potentials. Effects of RP 60180 were
      compared to placebo and to pentazocine that served as positive control. Twenty
      healthy male volunteers participated in a placebo-controlled, randomized, double
      blind, five-way cross-over study. Single peroral doses of RP 60180 (0.1, 0.5, and
      1.0 mg), pentazocine (50 mg), and placebo were administered. Pain was induced by
      means of short pulses of gaseous CO2 applied to the nasal mucosa. In response to
      these stimuli, chemo-somatosensory event-related potentials (CSSERP) and pain
      ratings were recorded. Maximum antinociceptive effects were observed 2 h after
      the administration of 1.0 mg of RP 60180 and 50 mg of pentazocine. This was
      shortly after RP 60180 had reached the maximum plasma concentration and when
      highest plasma concentrations of pentazocine were measured. Both RP 60180 and
      pentazocine reduced pain-related CSSERP amplitudes by approximately 40% at this
      time. Pentazocine tended to produce more side effects. These results indicate the
      potential therapeutic value of kappa-agonist analgesics.

PMID- 9197946
TI  - Prolactin response to bromocriptine in flunarizine-treated migrainous women.
AB  - Flunarizine, a calcium channel blocker, is widely used in migraine prophylaxis.
      Although an antidopaminergic effect has been suggested for this drug, it is
      unclear whether the antimigraine action of flunarizine involves the dopaminergic
      system. We studied the inhibitory response of prolactin to acute administration
      of bromocriptine, a D2 dopamine receptor agonist, before and after 1 month of
      treatment with flunarizine in migrainous women. Flunarizine treatment increased
      basal prolactin levels, but it did not reduce the inhibitory response of
      prolactin to acute bromocriptine administration. These findings do not support
      the hypothesis that flunarizine acts as a direct antagonist at the D2 dopamine
      receptor.

PMID- 9197947
TI  - Variations in axial, proximal, and distal motor response to L-dopa in multisystem
      atrophy and Parkinson's disease.
AB  - The purpose of this study was to quantitatively compare the motor response to L
      dopa in Parkinson's disease (PD) and striatonigral-type multisystem atrophy (MSA)
      patients. Ten consecutive MSA patients were compared with nine PD patients
      selected to have similar overall motor compromise, age, and mental state. The
      performance of simple repetitive axial movements plus bilateral proximal and
      distal limb movements; overall motor response assessed by the Unified Parkinson
      Disease Rating Scale (UPDRS); as well as scores from the UPDRS items evaluating
      speech/facial expression, postural stability, and posture/gait were assessed 90
      min and 12 h (baseline) after L-dopa administration. The total UPDRS score, all
      subcategory scores, and all body movements improved significantly in the PD
      group. Proximal and distal limb akinesias and speech/facial expression improved
      in some MSA patients. Lack of response of axial akinesia to L-dopa in MSA
      correlates with a presumed greater loss of postsynaptic dopaminergic receptors in
      the dorsolateral putamen, while improvement in distal and proximal limb muscle
      akinesias in MSA patients may be related to relative preservation of the ventral
      putamen.

PMID- 9197948
TI  - Long-term treatment with intermitent intranasal or subcutaneous apormorphine in
      patients with levodopa-related motor fluctuations.
AB  - Twenty patients with idiopathic Parkinson's disease and disabling motor
      fluctuations were treated with intermittent subcutaneous (11 patients) or
      intranasal (nine patients) apomorphine for > 2 years. Apomorphine significantly
      reduced the mean daily "off" hours in both groups (p < 0.01) and improved "off"
      dystonia and end-of-dose and diphasic diskinesias. Unlike others authors, we
      found no difference between intranasal and subcutaneous' groups of treatment in
      the mean dose of apomorphine required to turn "on." Tolerance phenomenon to
      apomorphine could not be demonstrated in the follow-up period. Nasal crusting and
      vestibulitis observed in some patients treated intranasally were the more severe
      side effects and determined that some of them either switched to subcutaneous
      therapy or abandoned the treatment.

PMID- 9197949
TI  - Multidrug comparison (lorazepam, triazolam, zolpidem, and zopiclone) in
      situational insomnia: polysomnographic analysis by means of the cyclic
      alternating pattern.
AB  - Since homogeneous samples of insomniacs are difficult to recruit for
      pharmacotherapy studies, normal sleepers can be used to assess the protective
      effect of hypnotic drugs, under standardized nonconducive conditions. In
      particular, a noisy environment is a typical cause of situational insomnia that
      can be counteracted by a sedative-hypnotic agent. Six healthy middle-aged
      subjects (three men and three women), with no complaints about sleep, underwent a
      completely randomized double-blind series of 10 nocturnal polysomnograms with at
      least 72-h washout intervals. All subjects received a single dose of placebo,
      zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both
      under basal and under perturbed conditions. For each individual, five recordings
      were carried out under basal conditions (sound pressure level not higher than 30
      dB) and five recordings under acoustically perturbed conditions (continuous white
      noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale
      (VAS). All recordings were scored according to conventional rules (macro
      structure) and cyclic alternating pattern (CAP) methodology (microstructure).
      Statistical analysis was based on a repeated measures analysis-of-variance design
      integrated by Bonferroni adjusted probabilities. Under placebo, situational
      insomnia was confirmed by the significant increase in sleep fragmentation
      (intrasleep wakefulness) and by the significant enhancement of arousal
      instability (CAP parameters). In contrast to macrostructural information, CAP
      parameters were highly sensitive in detecting the perturbing effects of noise
      (mean CAP rate under placebo, 57%) and the protective action of hypnotic drugs
      during perturbation (mean CAP rate under active medication, 41%). Microstructural
      analysis enabled us to discriminate hypnotic drugs from placebo,
      nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from
      zolpidem. The latter, in fact, induced the lowest values of CAP rate both under
      basal (30%) and under noisy (39%) conditions and determined a significant
      decrease in electroencephalogram arousals. All CAP parameters were significantly
      correlated with the visual-analogue-scale scores for sleep quality. The use of
      CAP methodology in a highly standardized model of situational insomnia can be a
      valid alternative to conventional sleep scoring for the investigation of drug
      effects on disturbed sleep.

PMID- 9197950
TI  - Lack of effect of methylphenidate on serum growth hormone (GH), GH-binding
      protein, and insulin-like growth factor I.
AB  - The aim of this study was to assess the growth hormone (GH) axis in
      methylphenidate (MPH)-treated and untreated boys with attention-deficit and
      hyperactivity disorder (ADHD), by evaluating serum GH, GH-binding protein (GHBP)
      activity, and insulin-like growth factor I (IGF-I) levels as compared to age
      matched normal controls. Blood samples were taken from 42 boys (aged 6-16 years)
      diagnosed as having ADHD according to DSM-III-R criteria and confirmed by using
      the Schedule for Affective Disorder and Schizophrenia for school-age children
      (K[Kiddle]-SADS). A total of 21 patients were treated with MPH (5-20 mg/day; 0.15
      0.77 mg/kg/day), on a drug holiday protocol, for 1-36 months, and 21 were drug
      naive. A total of 46 age-matched normal boys at height and weight within normal
      range served as controls. No significant differences were detected between the
      MPH-treated ADHD children, the untreated ADHD children, and the control children
      on fasting serum GH levels, GHBP activity, or IGF-I levels. Active treatment with
      MPH, in ADHD children on a drug holiday protocol, does not cause changes in GH
      axis as manifested by normal values of GH, GHBP, and IGF-I.

PMID- 9197951
TI  - Pupillary changes associated with the development of stimulant-induced mania: a
      case report.
AB  - A 30-year-old cocaine-dependent man who was a subject in a study evaluating the
      anticraving efficacy of the stimulant medication diethylpropion (DEP) became
      manic during his second week on the study drug. Pupillometric changes while on
      DEP, especially changes in the total power of pupillary oscillation, were
      dramatically different than those observed in the eight other study subjects who
      did not become manic. The large changes in total power of pupillary oscillation
      occurred a few days before the patient became fully manic. Such medication
      associated changes in the total power of pupillary oscillation might be of
      utility in identifying persons at risk for manic-like adverse effects during the
      medical use of psychomotor stimulants or sympathomimetic agents.

PMID- 9197952
TI  - Deprenyl, excess mortality, and epidemiological traps.
AB  - Compared with the findings for an age-matched group not taking deprenyl, a higher
      risk of mortality in Parkinson's disease patients taking deprenyl has recently
      been reported. Since a biological basis for this observation was not apparent, an
      epidemiological explanation was sought. Expected mortality over a 6-year period
      in four hypothetical age-matched groups was determined. Although groups were age
      matched, ages of individuals within the groups varied. Variation of individual
      ages within each group, without affecting the age-match comparability, produced a
      marked variation in expected group mortality. Mortality comparisons between age
      matched groups can be invalid. This epidemiological trap might account for the
      recent unexplained high mortality observed in a group of Parkinson's disease
      patients taking deprenyl.

PMID- 9197953
TI  - Intranasal neostigmine therapy of botulinum toxin (BTX) treatment dysphagia.

PMID- 9197954
TI  - Clozapine-fluroxamine interaction.

PMID- 9197955
TI  - Role of ear piercing in metal allergic contact dermatitis.
AB  - To evaluate the effect of ear piercing on sensitization to gold and other metals,
      diagnostic patch testing with 18 metals was performed. 377 patients (65 men and
      312 women, ranging in age from 15 to 78 years; mean 34.2, S.D +/- 15.1 years)
      were patch tested; 107 had pierced earlobes. Metals were applied on the back for
      2 days, and the results read with the ICDRG scoring system 3 days after
      application. Reactions of + to +3 were regarded as positive. There were
      significantly more patients reacting to gold chloride (p < 0.001), mercuric
      chloride and nickel sulfate (p < 0.05) in patients with pierced ears than in
      those without. Statistical issues included: (i) a significant number of patients
      with pierced ears referred because of earring dermatitis; (ii) those with pierced
      ears represented a different age group from those without; (iii) a significant
      number of patients without eczema in the non-pierced ear group. However, our data
      suggests that ear piercing is a risk factor not only for nickel but also for gold
      sensitization. Gold was the second most frequent metal allergen after nickel in
      the pierced group.

PMID- 9197956
TI  - Patch test materials for mercury allergic contact dermatitis.
AB  - The objective of this study was to define adequate patch test materials to
      evaluate mercury allergic contact dermatitis. We applied 0.1% and 0.05% mercuric
      chloride, and 0.5% and 0.2% mercury in petrolatum to systemic eczematous contact
      type dermatitis (baboon syndrome), and gold-dermatitis patients. All baboon
      syndrome patients reacted not only to mercuric chloride but also to metallic
      mercury. In gold-dermatitis patients, significantly more patients reacted to
      mercuric chloride than to metallic mercury (21 of 35, 60%, versus 2 of 19, 10.5%,
      p < 0.0005). We speculated that sensitization to mercury may be of 2 types: one a
      reaction to ionized mercury only, the other to both ionized mercury and non
      ionized mercury. The possibility that the phenomenon is caused by differences in
      bioavailability or percutaneous penetration between ionized and non-ionized
      mercury cannot be ruled out, but could be explored by penetration measurement.
      For the evaluation of mercury hypersensitivity, it may be more reliable to apply
      both ionized and non-ionized mercury, rather than only mercuric chloride or
      ammoniated mercury.

PMID- 9197957
TI  - Influence of temperature on irritation in the hand/forearm immersion test.
AB  - As indicated by in vitro experiments the penetration of irritants through the
      skin is significantly influenced by the temperature of the solution. In vivo
      experiments, demonstrated equally a significant influence of temperature in
      surfactant-induced skin irritation. In order to evaluate the irritant potential
      of detergent solutions under normal user conditions, we used the hand/forearm
      immersion test. We compared 2 detergents with different anionic character in a
      repetitive immersion protocol (30 min immersion on 4 consecutive days). The
      solutions were tested at 2 temperatures (37 degrees C and 40 degrees C). The
      irritation was quantified by assessment of the stratum corneum barrier function
      (transepidermal water loss), skin redness (a* colour parameter) and skin dryness
      (capacitance method). Both detergents affected the integrity of the skin in a
      significant way. The anionic content as well as the temperature of the solutions
      were found to be determinative for the irritant potential, with a stronger
      response for higher anionic content and temperature, respectively.

PMID- 9197958
TI  - A study of dermatitis in the lacquerware industry.
AB  - Contact dermatitis from lacquer has been documented. The causative agent is a
      resin from a lacquer tree that can induce either irritation or sensitization.
      Thai and Japanese lacquer trees are 2 distinct species but are both members of
      the Anacardiaceae family. We report 3 cases of contact dermatitis from Thai
      lacquer resin. Observation and study of the lacquer plantation and working
      process at the factory were made to elucidate the aetiology of the dermatitis.

PMID- 9197959
TI  - Shoe dermatitis.
AB  - Chronic foot dermatitis can be disabling and footwear allergy is not always
      excluded as a cause, partly because patch testing to shoes and their components
      can be daunting. Once the diagnosis of shoe allergy is made, the difficult
      problem of finding suitable footwear remains. There is a lack of literature
      regarding the follow-up of these patients. We analysed the data on 55 patients
      with allergic contact dermatitis from their shoes and followed them up to see
      whether knowledge of the allergen had enabled them to find suitable footwear and
      to improve their dermatitis. The files of 55 patients with shoe allergy were
      analysed and 48 were followed up. Rubber was the commonest allergen, followed by
      chromate, p-tertiary-butylphenol-formaldehyde resin and colophony. All parts of
      the feet were affected, except the interdigital areas. The majority of patients
      suffered from hyperhidrosis. 43% were atopics, who had a super-added shoe
      allergy. The mean duration of the foot dermatitis before patch testing was 4
      years 8 months. Follow-up of 48 cases showed that 87.5% had either improved or
      resolved completely. Most of our patients were successful in finding suitable
      footwear and many differing strategies were used. All patients with foot
      dermatitis which does not respond to treatment should be patch tested to exclude
      shoe allergy.

PMID- 9197960
TI  - The major allergen of Dendropanax trifidus Makino.
AB  - Dendropanax trifidus Makino (family Araliaceae, syn. Gilibertia trifida Makino)
      has been reported as causing allergic contact dermatitis in Japan. To identify
      the major allergen, fractionated extracts of fresh leaves of Dendropanax trifidus
      were patch tested on 2 patients with hypersensitivity to the plant. Cis-9,17
      octadecadiene-12,14-diyne-1, 16-diol (I), an analog of falcarinol, was identified
      as an active component. 18 normal control subjects were patch tested with the
      leaf of Dendropanax trifidus and I diluted to 0.05% in pet. 4 of them showed
      active sensitization to the leaf of Dendropanax trifidus and I. Our results
      suggest that I is the major allergen of Dendropanax trifidus and is a strong
      sensitizer. The results of patch testing on patients and control subjects with
      the leaves of Fatsia japonica Decne. et Planch. and Hedera helix L., which also
      belong to the Araliaceae family, and urushiol are also shown.

PMID- 9197961
TI  - Barrier recovery and influence of irritant stimuli in skin treated with a
      moisturizing cream.
AB  - Moisturizers are used daily by many people to alleviate symptoms of clinically
      and subjectively dry skin. Recent studies suggest that certain ingredients in
      creams may accelerate the recovery of a disrupted barrier and decrease the skin
      susceptibility to irritant stimuli. In the present single-blind study, a
      moisturizing cream was tested for its influence both on barrier recovery in
      surfactant-damaged skin and on the susceptibility of normal skin to exposure to
      the irritant sodium lauryl sulphate (SLS). Parameters measured were
      transepidermal water loss (TEWL) and skin corneometer values, indicating degree
      of hydration. Treatment of surfactant-damaged skin with the test cream for 14
      days promoted barrier recovery, as observed as a decrease in TEWL. Skin
      corneometer values also normalized more rapidly during the treatment. In normal
      skin, use of the test cream significantly reduced TEWL after 14 days of
      treatment, and irritant reactions to SLS were significantly decreased. Skin
      corneometer values increased after only 1 application and remained elevated after
      14 days. In conclusion, the accelerated rate of recovery of surfactant-damaged
      skin and the lower degree of SLS-induced irritation in normal skin treated with
      the test cream may be of clinical relevance in attempts to reduce contact
      dermatitis due to irritant stimuli.

PMID- 9197963
TI  - Recurrent oedematous irritant contact dermatitis of the eyelids from indirect
      application of glycolic acid.

PMID- 9197962
TI  - Patch testing in discoid eczema.
AB  - We report a retrospective study of patch testing in patients with discoid eczema.
      48 patients with persistent or severe discoid eczema were patch tested. The mean
      age of patients was 45 years and the median duration of symptoms was 6 months. 24
      patients (50%) had positive patch tests, and 16 of these (33%) were considered to
      be clinically relevant. The most common allergens implicated were rubber
      chemicals, formaldehyde, neomycin, chrome, nickel (5, 2, 2, 2, 2, 2 reactions,
      respectively). 13 of 16 patients were followed up by telephone in 1996, and 8/13
      (61%) stated they had benefited from patch testing. This study suggests allergic
      contact dermatitis is relatively common in persistent discoid eczema, and
      allergen avoidance may be of benefit. We recommend patch testing should be
      considered for all patients with severe or persistent discoid eczema.

PMID- 9197964
TI  - Nickel-induced lymphocytoma cutis of the earlobe.

PMID- 9197965
TI  - Contact dermatitis from nitrocellulose in a nail varnish.

PMID- 9197966
TI  - Airborne contact dermatitis from propacetamol.

PMID- 9197968
TI  - Multiple sources of allergic contact dermatitis from parabens.

PMID- 9197967
TI  - Allergic contact dermatitis from black cumin (Nigella sativa) oil after topical
      use.

PMID- 9197969
TI  - Allergic contact dermatitis due to methiocarb (Mesurol).

PMID- 9197970
TI  - Allergic contact dermatitis from diphenylthiourea in a wet suit.

PMID- 9197971
TI  - Occupational allergic contact dermatitis from 2-tert-butylamino-4
      cyclopropylamino-6-methylthio-1,3,5-triazine.

PMID- 9197972
TI  - Contact allergy to vitamin E capsules: false-negative patch tests to vitamin E?

PMID- 9197973
TI  - Airborne contact dermatitis due to methylchloro- and methylisothiazolinone
      (MCI/MI).

PMID- 9197974
TI  - Contact allergy in psoriasis.

PMID- 9197975
TI  - Pustular contact dermatitis from fluorine in an antirust solution.

PMID- 9197976
TI  - Erysipelas-like mercury exanthem.

PMID- 9197977
TI  - The relationship between clinical patterns, and exogenous and endogenous factors,
      in hand eczema.

PMID- 9197978
TI  - Structure-activity relationships in quinoline Reissert derivatives with HIV-1
      reverse transcriptase inhibitory activity.
AB  - The relationship between the chemical structure and the HIV-1 RT inhibitory
      activity has been studied for a series of quinoline derivatives. Two methods were
      used: a standard QSAR analysis, by combining the methods of Hansch and Free
      Wilson, and an analysis using quantum chemistry indices as descriptor parameters,
      by the semiempirical method AM1. The equations obtained lead to the proposal that
      the activity of the compounds increases, mainly, with the presence of electron
      withdrawing substituents in position 6 of the quinoline ring that cause a
      decrease in the energy from the molecular orbital LUMO. In turn, this fact leads
      to the proposal that the most important interaction of these compounds with the
      HIV-1 RT is a charge transfer type interaction, with the quinoline aromatic ring
      acting as acceptor.

PMID- 9197979
TI  - Thienocycloheptapyridazines as new muscarinic agents.
AB  - A series of thienocycloheptapyridazines (3aa-dd), structurally related to
      Minaprine, was synthesized and compounds tested for their affinity towards
      muscarinic receptors. All of them showed Ki values in the micromolar range
      towards both the antagonist 3H-QNB and the agonist 3H-OXO-M, thus indicating that
      they act as antagonists at the muscarinic receptors. Moreover a theoretical study
      was performed on their interaction behaviour with a three dimensional (3-D) model
      of the human m1 muscarinic receptor.

PMID- 9197980
TI  - Synthesis and evaluation of new Reissert analogs as HIV-1 RT inhibitors. 2.
      Benzo[f]quinoline and pyridine derivatives.
AB  - The synthesis and preliminary evaluation of new benzo[f]quinoline and pyridine
      derivatives, obtained by application of the Reissert method and its
      modifications, as HIV-1 RT inhibitors and anti-infectives are presented. The most
      active products against HIV-1 RT wild type are the ethyl 2-cyano-1,2
      dihydrobenzo[f]quinoline-1-carboxylate 2b, propyl 2-cyano-1,2
      dihydrobenzo[f]quinoline-1-carboxylate 2c, and 2-cyano-1-(2'-furoyl)-1,2
      dihydrobenzo[f]quinoline 2n, which maintain their activity against the mutant
      type P236L, resulting inactive against the Y181C type. Using the data previously
      obtained by our research team for analogous series derived from quinoline as
      reference, the compounds which have now been obtained present an increase in the
      cytotoxic character attributable to the introduction of a benzene ring fused with
      the quinoline base nucleus, as well as a decrease of the activity as HIV-1 RT
      inhibitors when the quinoline benzenic ring is eliminated.

PMID- 9197981
TI  - Synthesis and evaluation of new Reissert analogs as HIV-1 reverse transcriptase
      inhibitors. 1. Quinoline and quinoxaline derivatives.
AB  - The synthesis and preliminary evaluation of new quinoline and quinoxaline
      derivatives (obtained by applying the original Reissert method, conveniently
      modified) as HIV-1 Reverse Transcriptase (RT) inhibitors are presented in this
      paper; likewise, the first structure-activity relationships are also proposed.
      Propyl 2-cyano-1(2H)-quinolin-carboxylate 2e, isopropyl 2-cyano-1 (2H)
      quinolincarboxylate 2f, butyl 2-cyano-1 (2H)-quinolincarboxylate 2g and isobutyl
      2-cyano-1 (2H)-quinolincarboxylate 2h have been selected as lead compounds. These
      compounds are active against the HIV-1 RT mutant type P236L (2f, IC50 = 1.2
      microM) and present activity as anti-infective agents in HLT41acZ-1IIIB cells,
      showing no cytotoxicity at the active concentrations.

PMID- 9197983
TI  - The European Histamine Research Society: a silver anniversary.

PMID- 9197982
TI  - [Repeat evaluation of impulsiveness in a cohort of 155 patients with obsessive
      compulsive disorder: 12 months prospective follow-up].
AB  - Relationships between OCD and impulsivity are currently under research. METHOD:
      In the phase 3 of the national study on OCD, 155 patients suffering from an OCD
      (DSM III-R criteria, score on NIMH-OC > or = 7) had entered a naturalistic follow
      up of 12 months duration. Impulsivity was assessed by using the BDS (Behavioral
      Dyscontrol Scale, offautoquestionnaire of 24 items) at day 0, 6th and 12th months
      and a semi-structured interview for Obsessive-Compulsive Related Syndrome and
      Behaviors Spectrum, as defined by Hollander (DSM III-R criteria). RESULTS:
      Impulsivity was more intense in females (mean score on BDS 35.6 vs 31.9, p =
      0.06), in patients with personal history of anxiety-depression (36.3 vs 32.3, p =
      0.04) and suicidal behavior (38.3 vs 33.2, p = 0.06) and familial history of OCD
      (37.1 vs 33.0, p = 0.07). Moreover, syndromal typology of obsessions or
      compulsions did not seem to influence impulsivity. In contrast, presence of co
      existing OC Related Syndrome was significantly linked to higher impulsivity
      score, especially with "Intermittent Explosive Syndrome" (mean score = 40.1 vs
      30.8, p < 10(-4), "Compulsive Buying" (38.5 vs 32.4, p = 0.005),
      "Hypochondriasis" (36.7 vs 32.1, p = 0.02), "Dysmorphophobia" (37.1 vs 32.4, p =
      0.02) and "Depersonnalization" (37.7 vs 32.9, p = 0.05). Paradoxically,
      impulsivity was augmented in patients with important to severe slowness syndrome
      (38.3 vs 31.8, p = 0.001). This mixed association between slowness and
      impulsivity can be an excellent testimony of "Dyscontrol" phenomenon. In 130
      patients who had received an anti-obsessional pharmacologic treatment during 12
      months follow-up, impulsivity score was gradually reduced from day 0 (mean score
      = 34.1) at M6 (24.8-22% reduction) and at M12 (20.1-36% reduction). After one
      year of follow-up, a decreased by > or = 50% of impulsivity score was observed in
      42% of obsessional patients. Finally, the response rate of OCD to pharmacotherapy
      seemed to be modulated by the dimensions of impulsivity and slowness. In fact,
      the best results after 6 months of treatment were observed in the sub-groups
      presenting high level of "impulsivity" (62-66% were responders) versus 39% in the
      sub-group with important to severe slowness.

PMID- 9197984
TI  - Angiogenesis in inflammatory disease.

PMID- 9197986
TI  - Induction of plasma hepatocyte growth factor in acute colitis of mice.
AB  - OBJECTIVE AND DESIGN: The study examined plasma levels of hepatocyte growth
      factor (HGF) in acute colitis models on mice. MATERIALS: Acute colitis was
      induced in male FVB mice (about 25 g) by intrarectal administration of 200
      microliters of 0.5% acetic acid. METHODS: Plasma was taken at 0, 12, 24, 36, 48
      and 72 h after acetic acid treatment. Plasma HGF was measured by an enzyme
      immunoassay in duplicate. RESULTS: Plasma levels of HGF at 0, 12, 24, 36, 48 and
      72 h after acetic acid administration were 0.31 +/- 0.11 ng/ml (n = 4), 0.45 +/-
      0.04 ng/ml (n = 4), 0.46 +/- 0.13 ng/ml (n = 4), 0.71 +/- 0.22 ng/ml (n = 4),
      0.82 +/- 0.15 ng/ml (n = 4) and 0.44 +/- 0.04 ng/ml (n = 4), respectively.
      Significant increases in plasma HGF levels were observed at 36 and 48 h after the
      treatment (p < 0.05, compared to at 0 h). CONCLUSIONS: Plasma HGF was induced by
      acute inflammation of colonic tissues. These findings suggest that HGF in blood
      may be one of the non-specific markers of inflammation in mice.

PMID- 9197985
TI  - The physiological role of histamine in the exocrine pancreas.
AB  - In addition to the autonomic nervous system and gut hormones, the mast cell
      mediator histamine has also been associated with exocrine pancreatic secretion.
      This review is concerned with the distribution and the physiological role of
      histamine in the control of pancreatic juice secretion. Histamine is distributed
      widely around blood vessels and acinar tissues in the pancreas and it is released
      in pancreatic juice during secretagogue stimulation. Histamine has a marked
      secretagogue effect in the exocrine pancreas of several animal species but in
      many cases the secretory effect is gender-related. The paracrine hormone exerts
      its secretory response via activation of H1 and H2 receptors on pancreatic acinar
      cells to mobilize potassium ions (K+) and cellular calcium (Ca2+) and through
      elevation of endogenous adenosine 3',5' cyclic monophosphate (cyclic AMP) levels,
      respectively. A physiological role for H3 receptors has also been associated with
      exocrine pancreatic secretion. H3 receptors are located presynaptically on
      parasympathetic nerve terminals to control the release of acetylcholine via
      restriction of Ca2+ access into nerve terminal through the N-type Ca2+ channel.
      Taken together, the results presented in this review strongly support histamine
      as a potential modulator of exocrine pancreatic function.

PMID- 9197987
TI  - Tenidap inhibits 5-lipoxygenase product formation in vitro, but this activity is
      not observed in three animal models.
AB  - OBJECTIVE AND DESIGN: The effect of tenidap on the metabolism of arachidonic acid
      via the 5-lipoxygenase (5-LO) pathway was investigated in vitro and in vivo.
      MATERIALS AND TREATMENT: In vitro (cells). Arachidonic acid (AA) stimulated rat
      basophilic leukemia, (RBL) cells; A23817 activated neutrophils (human rat, and
      rabbit), macrophages (rat), and blood (human). In vitro (enzyme activity). RBL
      cell homogenate; purified human recombinant 5-LO. In vivo: Rat (Sprague-Dawley)
      models in which peritoneal leukotriene products were measured after challenge
      with zymosan (3 animals per group), A23187 (11 animals per group), and immune
      complexes (3-5 animals per group), respectively. METHODS: 5
      Hydroxyeicosatetraenoic acid (5-HETE) and dihydroxyeicosatetraenoic acids
      (diHETEs, including LTB4) were measured as radiolabeled products (derived from
      [14C]-AA) or by absorbance at 235 or 280 nm, respectively, after separation by
      HPLC. Radiolabeled 5-HPETE was measured by a radio-TLC analyser after separation
      by thin layer chromatography (TLC). Deacylation of membrane bound [14C]-AA was
      determined by measuring radiolabel released into the extracellular medium. 5-LO
      translocation from cytosol to membrane was assessed by western analysis. Rat
      peritoneal fluid was assayed for PGE, 6-keto-PGF1 alpha, LTE4 or LTB4 content by
      EIA and for TXB2 by RIA. RESULTS: Tenidap suppressed 5-LO mediated product
      production in cultured rat basophilic leukemia (RBL-1) cells from exogenously
      supplied AA, and in human and rat neutrophils, and rat peritoneal macrophages
      stimulated with A23187 (IC50, 5-15 microM). In addition, tenidap was less potent
      in inhibiting the release of radiolabeled AA from RBL-1 cells (IC50, 180 microM),
      suggesting that the decrease in 5-LO derived products could not be explained by
      an effect on cellular mobilization of AA (i.e., phospholipase). Tenidap blocked 5
      hydroxyeicosatetraenoic acid (5-HETE) production by dissociated RBL-1 cell
      preparations (IC50, 7 microM), as well as by a 100000 x g supernatant of 5
      LO/hydroperoxidase activity, suggesting a direct effect on the 5-LO enzyme
      itself. In addition, tenidap impaired 5-LO translocation from cytosol to its
      membrane-bound docking protein (FLAP) which occurs when human neutrophils are
      stimulated with calcium ionophore, indicating a second mechanism for inhibiting
      the 5-LO pathway. Surprisingly, tenidap did not block the binding of radiolabeled
      MK-0591, an indole ligand of FLAP, to neutrophil membranes. Although its ability
      to inhibit the cyclooxygenase pathway was readily observed in whole blood and in
      vivo, tenidap's 5-LO blockade could not be demonstrated by ionophore stimulated
      human blood, nor after oral dosing in rat models in which peritoneal leukotriene
      products were measured after challenge with three different stimuli. The presence
      of extracellular proteins greatly reduced the potency of tenidap as a 5-LO
      inhibitor in vitro, suggesting that protein binding is responsible for loss of
      activity in animal models. CONCLUSIONS: Tenidap inhibits 5-lipoxygenase activity
      in vitro both directly and indirectly by interfering with its translocation from
      cytosol to the membrane compartment in neutrophils. A potential mechanism for the
      latter effect is discussed with reference to tenidap's ability to lower
      intracellular pH. Tenidap did not inhibit 5-LO pathway activity in three animal
      models.

PMID- 9197988
TI  - Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and
      in vivo.
AB  - OBJECTIVE: To investigate the effects of adenosine receptor agonists and
      antagonists on 5-HT release from rat isolated pleural mast cells and on plasma
      protein extravasation in the skin of conscious rats. In vitro METHODS: Rat
      isolated pleural mast cells were loaded with [14C] 5-HT, sensitised with mouse
      monoclonal anti-DNP and then challenged with human serum albumin-DNP. DNP
      stimulated 5-HT release from mast cells was determined. In vivo METHODS: Rats,
      loaded intravenously with [125I] human serum albumin, were injected intradermally
      with adenosine agonists at sites on the back. 30 min later plasma protein
      extravasation at each injection site was determined. RESULTS: In isolated mast
      cells, each adenosine agonist enhanced DNP-induced 5-HT release, N6-(3
      iodobenzyl)-5-(N-methyl-carboxamidoadenosine), (IB-MECA), being the most potent
      agonist. The adenosine A1/A2 antagonist, 8-phenyltheophylline (8-PT), had no
      effect on the response to IB-MECA. In contrast, 3-(4-amino-iodobenzyl)-8-[4
      [[[carboxy]methyl]oxy]phenyl]-1-propylxanthi ne, (I-ABOPX), inhibited (pA2 6.2)
      the IB-MECA responses. In the skin of conscious rats, intradermal IB-MECA
      produced a marked plasma protein extravasation (PPE) which was mimicked by N6-2
      (4-aminophenyl)-ethyladenosine (APNEA). The PPE produced by IB-MECA was not
      affected by either 8-PT or CGS15943A, but was virtually abolished by
      cyproheptadine and in rats pre-treated with Compound 48/80. CONCLUSIONS: These
      results indicate that stimulation of adenosine A3 receptors both enhances
      degranulation in vitro and directly produces degranulation of rat mast cells in
      vivo.

PMID- 9197990
TI  - Cardiovascular reactivity during verbal communication: an emerging risk factor.
AB  - Cardiovascular reactivity (CR), the abrupt increase in blood pressure and heart
      rate that occurs during stress, is emerging as a potential risk factor for
      hypertension and coronary heart disease. This article reviews the research on CR
      to verbal communication, an everyday stressor. A case study is presented to
      illustrate the usefulness of this research to clinical practice. Strategies to
      decrease CR during talking are presented.

PMID- 9197989
TI  - Dietary modulation of fatty acid composition of mast cell phospholipids does not
      affect histamine release induced by compound 48/80.
AB  - OBJECTIVE AND DESIGN: In the present study we determined the extent to which the
      degranulation process in mast cells was related to the fatty acid composition of
      membrane phospholipids. MATERIAL: Peritoneal mast cells were isolated from Wistar
      rats (3 groups of 18 animals each), fed for 6 weeks diets which differed in their
      fatty acid compositions: (i) genuine salmon oil, abundant in (n-3) fatty acids,
      (ii) sunflower seed oil, rich in (n-6) fatty acids, particularly linoleic acid,
      and (iii) hydrogenated coconut oil, rich in saturated fatty acids. METHODS: Mast
      cells (10(6)/ml) were stimulated with various concentrations of the mast cell
      degranulating agent, compound 48/80 (0.1-10 micrograms/ml). The extent of mast
      cell degranulation was quantified by determination of histamine in the
      supernatants using HPLC techniques. RESULTS: No differences in compound 48/80
      induced histamine release between the three dietary groups for any of the
      concentrations of compound 48/80 tested were found. Analysis of variance followed
      by Tukey's method for multiple comparisons was used to evaluate the effect of
      changes in the dietary fat type. CONCLUSION: These findings strongly suggest that
      in contrast to the formation of eicosanoids, the process of mast cell
      degranulation by a receptor-independent pathway is not controlled by the fatty
      acid composition of membrane phospholipids.

PMID- 9197991
TI  - Life-style changes and coronary heart disease: the influence of nonpharmacologic
      interventions.
AB  - Life-style habits such as diet and exercise can have powerful affects on the
      development and progression of coronary heart disease. This article presents
      evidence supporting the use of these two modalities in the treatment of coronary
      heart disease. Diet is discussed in terms of cholesterol, obesity, fiber, fish
      oils, and antioxidants. Exercise is discussed in terms of the preparation for and
      the components of an exercise program. Appropriate nursing interventions are
      offered for use when working with patients who must modify their dietary or
      exercise habits.

PMID- 9197992
TI  - Smoking cessation for the hospitalized cardiac patient: rationale for and report
      of a model program.
AB  - Smoking is the leading cause of preventable death in the United States, and
      smoking-related diseases are involved in more than one third of all hospital
      admissions. Smoking cessation has immediate and major health benefits for all
      individuals. Studies have demonstrated that a substantial reduction in mortality
      and morbidity can be achieved by abstinence from smoking. Interventions to reduce
      smoking must become a priority for health care providers, as physicians and
      nurses have the opportunity to interact with millions of smokers each year. The
      purpose of this article is to outline intervention strategies that nurses can use
      with smokers to encourage compliance with hospital smoking policies and to
      facilitate long-term abstinence from smoking.

PMID- 9197993
TI  - Drug therapy for hypertension and hyperlipidemia.
AB  - Coronary heart disease and other vascular complications of hypertension and
      hyperlipidemia are leading causes of morbidity and mortality and adding to health
      care costs in the United States. Nonpharmacologic and pharmacologic treatment are
      available and have been successful in reducing the frequency and severity of
      these conditions. Appropriate detection, confirmation, evaluation, and treatment
      of at-risk individuals by the health care provider are the focus of the
      discussion that follows.

PMID- 9197994
TI  - Evaluation of a nurse-based hypertension management program: screening,
      management, and outcomes.
AB  - This article reports the experience of patients with elevated blood pressure
      scheduled to be seen in a nurse-based hypertension management program in a large
      multispecialty group practice. The hypertension management program is a screening
      and follow-up program designed to improve the measurement and management of
      patients' blood pressure with standardized protocols. The cohort for this study
      of the effectiveness of the hypertension management program consisted of 200
      patients with elevated blood pressure (140 referred directly for management and
      counseling, 60 entered through screening). At entry, only 17% of the patients had
      blood pressure within controlled limits (< 140/90 mm Hg). One year after entry in
      the management phase of the program, systolic pressure had decreased an average
      of 6.20 mm Hg (P < 0.01), and 44% of patients had blood pressure within
      controlled limits (P < 0.001). These results suggest that the use of standardized
      screening techniques using multiple measurements helps to ensure that patients
      will not be unnecessarily treated. Furthermore, patients who entered the program
      successfully lowered their blood pressure and maintained the reduction over time.

PMID- 9197995
TI  - Adherence to medication, diet, and activity recommendations: from assessment to
      maintenance.
AB  - Inadequate adherence to treatment regimens has been a concern of health care
      providers for more than two decades. However, it continues to have a significant
      impact on morbidity and health care cost. Poor adherence crosses ethnic and age
      groups, socioeconomic strata, acute and chronic diseases, and treatment regimens.
      Depending on the population, the prescribed regimen, and the definition or
      measure of adherence used, rates vary from 10% to 85%. The consequences of absent
      or partial adherence are observed in the research arena and all types of clinical
      settings. Educational and behavioral strategies may prevent or remediate
      adherence problems.

PMID- 9197996
TI  - Treatment of the patient with primary familial heterozygous hypercholesterolemia.
AB  - Familial heterozygous hypercholesterolemia (FH) is a genetically linked lipid
      disorder that involves elevations in total cholesterol and LDL cholesterol. About
      5% of patients with coronary heart disease have FH. Treatment options include
      dietary therapy, weight optimization, exercise, and drug treatment. A case study
      of a patient who has undergone 4 years of treatment for FH after a diagnosis of
      coronary heart disease is presented. Nursing care was instrumental in the
      patient's compliance with and adherence to the treatment plan.

PMID- 9197997
TI  - Focus on research utilization.
AB  - This column focuses on research utilization in future issues. In this article,
      the coeditors of this column review the differences between the conduct of
      research and research utilization, describe the decision-making process for
      research utilization, and discuss the Agency for Health Care Policy and Research
      Clinical Practice Guidelines.

PMID- 9197998
TI  - Elucidation of the basic three-dimensional structure of type I interferons and
      its functional and evolutionary implications.
AB  - The scientific and personal backgrounds of the crystallographic elucidation of
      the three-dimensional structure of murine interferon-beta (Mu-IFN-beta) are
      described. This structure, elucidated in 1990, is still the only experimentally
      determined structure for type I IFNs. Model-building studies for various type I
      IFNs based on the Mu-IFN-beta structure and the arguments on the receptor-binding
      epitopes appearing since then are reviewed. An updated set of a table and a
      figure demonstrating a strong correlation between the degree of amino acid
      sequence variation in various cytokine proteins and that in their cognate
      receptor proteins is given. The origin of a remarkably larger rate of
      evolutionary change in amino acid sequences of cytokine proteins despite their
      physiologic significance is discussed in view of the cytokine network and the
      neutral theory of evolution.

PMID- 9197999
TI  - A comparison of the antiproliferative properties of recombinant human IFN-alpha 2
      and IFN-omega in human bone marrow culture.
AB  - We compared the antiproliferative effects in vitro of recombinant preparations of
      interferon-alpha 2c (IFN-alpha 2) and IFN-omega on the formation of colonies from
      bone marrow progenitor cells. Both IFNs led to statistically indistinguishable
      dose-dependent inhibitory effects when tested on bone marrow cells derived from 8
      normal donors or from 7 patients with chronic myelogenous leukemia (CML). With
      both IFNs, the cells from CML patients appeared slightly but not significantly
      more sensitive to inhibition than the cells from normal donors. These results
      suggest that under some circumstances, IFN-omega may prove an effective treatment
      for CML, for example, in those becoming resistant to IFN-alpha 2 because of the
      formation of neutralizing antibodies.

PMID- 9198000
TI  - Bidirectional effects of IFN-gamma on growth of Mycobacterium avium complex in
      murine peritoneal macrophages.
AB  - The effects of macrophage stimulation with interferon-gamma (IFN-gamma) before or
      after infection on the intracellular growth of Mycobacterium avium complex (MAC)
      were investigated. Treatment of murine peritoneal macrophages before infection
      with IFN-gamma (50 U/ml) for 24 h and 48 h, but not for 72 h, was associated with
      41% and 52% significant MAC growth inhibition, respectively. NG-monomethyl-L
      arginine (NMA) did not affect the preinfection antimycobacterial activity of IFN
      gamma, thus indicating that nitric oxide was not involved in this phenomenon. In
      contrast, treatment of macrophages with IFN-gamma (50 U/ml) for 24 h and 48 h
      after infection was ineffective, whereas treatment for 72 h caused some MAC
      growth promotion. The use of NMA suppressed the IFN-gamma-mediated MAC growth,
      suggesting that nitric oxide may affect postinfection microbicidal function of
      macrophages. These results suggest that activation of macrophages with IFN-gamma
      before or after infection may direct the course of the infection and that nitric
      oxide may be detrimental more than beneficial for MAC-infected macrophages.

PMID- 9198001
TI  - Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates
      expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial
      cells.
AB  - Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor
      found in human plasma and is a potent elastase inhibitor in various tissues,
      including lung. A1-Pi is expressed and induced in liver during inflammatory
      responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi
      production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such
      as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the
      role of these cytokines in regulating A1-Pi in lung epithelial cells. We show
      that OM, a monocyte and T cell product, can specifically and potently induce A1
      Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in
      liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western
      blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was
      also able to stimulate the expression of tissue inhibitor of metalloproteinase-1
      in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF)
      had little or no effect on A549 cells, and proinflammatory cytokines, such as IL
      1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect
      on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a
      decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6
      production was synergistically enhanced. OM was also able to stimulate A1-Pi
      production from a bronchial epithelial primary cell line, whereas an intestinal
      epithelial cell line HT29 responded to IL-6 but not OM. These results suggest
      that lung levels A1-Pi could be derived not only from liver and inflammatory
      cells but also from epithelial cells, which can be upregulated on stimulation by
      OM. This may have implications for regulation of local activity of human
      neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis.

PMID- 9198002
TI  - Effects of interferons on the production of interleukin-6 and interleukin-8 in
      human keratinocytes.
AB  - Interferons (IFNs) originally described for antiviral activity have been reported
      to have pleiotropic effects, including the ability to induce interleukin-6 (IL-6)
      and IL-8 production in several cell types. IL-6 and IL-8 are proinflammatory
      cytokines and are known to be produced by a wide variety of cells, including
      human keratinocytes. In the present study, we sought to examine the effects of
      IFNs on IL-6 and IL-8 production from human keratinocytes. IFN-gamma (10-50
      ng/ml) induced IL-6 and IL-8 production dose dependently, but no induction of IL
      6 or IL-8 was observed with either IFN-alpha or IFN-beta. Because cytokines often
      work in a cascade fashion and keratinocytes are a source of primary cytokines, IL
      1 alpha, and tumor necrosis factor-alpha (TNF-alpha), we examined whether
      combined treatment with IFN-gamma and these primary cytokines, IL-1 alpha and TNF
      alpha, had a synergistic effect on the production of IL-6 and IL-8. Combined
      treatment with IFN-gamma and IL-1 alpha induced 6-fold to 7-fold higher levels of
      IL-6 than IL-1 alpha alone. Combined treatment with IFN-gamma and TNF-alpha
      induced 11-fold to 12-fold higher levels of IL-6 than TNF-alpha alone. The same
      treatment induced 3-fold to 4-fold higher levels of IL-8 in both cases. These
      results suggest that IFN-gamma is a positive regulator for the production of IL-6
      and IL-8 from human keratinocytes and likely has an augmentative effect on skin
      inflammation.

PMID- 9198003
TI  - Interferon-beta induces S phase accumulation selectively in human transformed
      cells.
AB  - Interferons (IFNs) generally have been characterized as antiproliferative
      cytokines. The cell cycle arrest in G1/G0 phase induced by type I IFNs,
      especially IFN-alpha, was recognized as a manifestation of their
      antiproliferative effects. In this article, we report that the cell cycle block
      in G1/G0 is observed mainly in certain cell types, such as Daudi Burkitt's
      lymphoma cells. In a variety of human transformed cells, but not nontransformed
      primary cells, IFN-beta and IFN-alpha induced a significant increase in the S
      phase population. The increase appeared to be due to a continued S phase entry
      and subsequently a failure of S phase cells to transit efficiently into G2 and M
      phases. The ability of tumor cells to exhibit the S phase effect correlated with
      proper IFN signaling and loss or inactivation of the normal G1 checkpoint
      conferred by the retinoblastoma protein (pRB). Overriding the G1 checkpoint
      switched human nontransformed primary cells from nonresponsive to sensitive to
      the IFN-induced effect. Therefore, the cell cycle regulatory machinery could
      function, at least in part, as a determining factor that affects the IFN-induced
      cell cycle effect. The IFN effect in transformed cells may suggest intriguing
      prospects for combinatorial therapies for cancer.

PMID- 9198004
TI  - Expression of Fas and Fas ligand in renal grafts with acute and chronic rejection
      in the rat model.
AB  - The Fas system-based rejection mechanism has not been studied well in terms of
      cytotoxic T cell activity in graft rejection. We investigated the Fas and Fas
      ligand level in renal grafts with acute and chronic rejection in a rat model
      using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
      Fas ligand in renal allografts was detected as early as 1 day after
      transplantation in an acute rejection model. It was highly expressed at day 4 and
      began to decline at day 6 after transplantation. In contrast, Fas ligand in
      normal kidneys was almost undetectable. Fas ligand in isografts was increased,
      but the expression level was much lower than in allografts. Interestingly, when
      Fas ligand expression began to decline in renal allografts, it increased in the
      spleens of recipients. Fas ligand expression in chronically rejecting allografts
      was slightly increased, but it was stronger than in isografts. In contrast to Fas
      ligand gene expression, Fas was constitutively expressed in isografts,
      allografts, and normal kidneys. However, the Fas level in renal allografts was
      higher than in normal kidneys. Our data demonstrated that the Fas system might
      play an important role in acute and chronic rejection by causing apoptosis, and
      the spleen may eliminate the lymphocytes strongly expressing Fas ligand after
      completion of the acute rejection.

PMID- 9198005
TI  - An overview of animal toxicology studies with bicalutamide (ICI 176,334).
AB  - The toxicological profile of bicalutamide in animals following acute and chronic
      dosing is closely associated with the drug's non-steroidal anti-androgenic
      pharmacological activity. Bicalutamide produces typical effects of an anti
      androgen, including atrophy of the prostate, testis and seminal vesicles and
      Leydig cell hyperplasia resulting from inhibition of pituitary feedback by
      testosterone. Subsequent benign Leydig cell tumors were seen in rats, but Leydig
      cell hyperplasia has not been observed in patients. Bicalutamide causes liver
      enlargement and is a mixed function oxidase inducer in rodents and dogs, but not
      man. These effects lead to thyroid hypertrophy and adenoma in the rat and
      hepatocellular carcinoma in the male mouse. In vitro and in vivo genotoxicity
      studies have all given negative results. Bicalutamide also caused a reversible
      shortening of the electrocardiographic P-R interval in the dog without any
      associated pathology. This change was not detected in ECG monitoring during
      clinical trials. In conclusion, bicalutamide produced a range of pharmacological
      effects, as well as liver enlargement with enzyme induction and dog ECG changes
      in preclinical toxicity studies in rodents and dogs. Only the pharmacological
      changes were found to be relevant to human usage.

PMID- 9198006
TI  - A safety study on rat's eye after 13-week oral administration with fenitrothion.
AB  - The potential of ocular toxicity of fenitrothion (O,O-dimethyl O-4-nitrom-tolyl
      phosphorothioate) was assessed in Sprague-Dawley (Crj:CD) rats of both sexes
      receiving a diet containing the test compound at concentrations of 0, 2.5, 5, 10,
      or 30 ppm for 13 weeks. The animals were observed daily for clinical signs and
      their body weights and food consumption were measured weekly during the study. At
      termination of treatment, surviving animals were subjected to ophthalmoscopy,
      electroretinography, and biochemical analyses of plasma, erythrocyte, and brain
      cholinesterase (ChE). Histopathological examinations of ocular tissues were
      performed on all animals by light microscopy and on two animals/sex/dose by
      electron microscopy. There were no treatment-related changes in clinical signs,
      body weights, and food consumption. A significant inhibition of ChE activity was
      observed in males (plasma and erythrocyte ChE) and females (plasma, erythrocyte,
      and brain ChE) at 30 ppm and in females (plasma ChE) at 10 ppm. Ophthalmological
      and histopathological examinations revealed neither functional nor morphological
      alterations in the visual system at any dose level. Under the conditions of the
      present study, there was no evidence of ocular toxicity of fenitrothion for male
      and female rats at dose levels up to 30 ppm (1.70 mg/kg/day for males and 1.96
      mg/kg/day for females) where distinct inhibition of ChE activity was observed.

PMID- 9198007
TI  - Transfer of leptophos in hen eggs and tissues of embryonic rats.
AB  - To estimate the delayed neurotoxic effect of OPs on the next generation, we tried
      two examinations; one was on the distribution of leptophos in tissues and eggs of
      hens which are highly susceptible to the delayed neurotoxic effect of OPs but
      have no placenta, and the other was on the concentration of OPs in tissues of
      both pregnant and embryonic rats which are not susceptible to the delayed
      neurotoxic effect but have placenta, after leptophos was administered to the
      mother in both experiments. First, organophosphorus compound-induced delayed
      neurotoxicity (OPIDN) was checked in 4 hens and the concentration of leptophos
      was determined in the other 16 hens after 20 adult laying hens were given 30
      mg/kg leptophos (iv), a neurotoxic organophosphate. Three out of 4 hens treated
      with leptophos showed OPIDN. The concentration of leptophos decreased sharply in
      the blood, liver, brain and spinal cord from 24 to 48 hr after leptophos
      administration, but clearance of leptophos was relatively slow in the ovary.
      Leptophos in laid egg yolk was detected every day for 10 days, and the highest
      concentration of leptophos in egg yolk was observed on the 6th day after
      administration to hens. Secondly, in order to investigate the transfer of
      leptophos to the embryo through the placenta, we divided the thirty-two pregnant
      rats into 2 groups. The first group received 10 mg/kg leptophos intraperitoneally
      on the 17th day of pregnancy and the second received 20 mg/kg leptophos on the
      same day. The time-course of leptophos concentration in the tissues of pregnant
      and embryonic rats was checked, and the correlation between findings in the
      pregnant rats and the embryos was determined. The time-course of leptophos
      concentration in the blood, liver, brain and placenta of the rats was similar to
      that in hens. Leptophos concentration in the liver and brain of the embryos was
      equal to approximately 60% of leptophos concentration in each tissue of the
      pregnant rats, and the concentration of leptophos in the liver and brain of
      embryonic rats correlated with that in the blood and placenta of pregnant rats (p
      < 0.01). In both groups treated with 10 and 20 mg/kg leptophos, the
      concentrations of leptophos in the liver and brain of embryos were lower than
      that of pregnant rats in the early period after dosing, but the concentrations in
      embryos were inversely higher than those in pregnant rats in the latter period
      (48 hr). Compared with the biological half-lives of leptophos in the liver and
      brain of pregnant rats, these parameters in embryonic rats were 1.58 and 1.87
      times, respectively. These results indicate that some of the fat-soluble
      organophosphorus compounds readily pass through the blood-placenta barrier into
      the embryos and accumulate there. Therefore, the neurobehavioral development of
      F1 rats exposed to some organophosphorus compounds through the placenta of
      pregnant rats should be further examined.

PMID- 9198008
TI  - Low activity of aldehyde dehydrogenase (ALDH) in liver of Suncus murinus:
      possible explanation for high sensitivity to alcohol.
AB  - Suncus murinus (suncus) is an animal species highly sensitive to ethanol (Lin, S.
      C., Saito, H., Yohro, T. and Shiga, J.,J. Toxicol. Env. Health, 18: 575-587,
      1986). To elucidate the mechanism involved in sensitivity to alcohol, we
      investigated that properties of alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH) in the suncus in comparison with the rat. The activities of
      ALDH in microsomes and mitochondria of suncus livers were lower than those in rat
      livers, although the activity of cytosolic ADH was not different between the
      suncus and the rat. We propose that the high sensitivity of the suncus to alcohol
      can be accounted for, at least in part, by the low activity of ALDH in suncus
      liver.

PMID- 9198009
TI  - Single and repeated intravenous toxicity studies of pamiteplase (genetical
      recombination) in rats and monkeys.
AB  - Single and repeated intravenous toxicity studies of Pamiteplase (genetical
      recombination) YM866, a novel recombinant human tissue-type plasminogen
      activator, were conducted. No animal died from toxic effects of YM866 after
      single administration to F344 rats, squirrel monkeys and cynomolgus monkeys. Male
      and female F344 rats were given YM866 intravenously for 4 weeks at doses of 0
      (vehicle), 0.1, 0.3 and 1 mg/kg/day. An increase in platelet count, slight
      decreases in hemoglobin and hematocrit, increases in plasma phospholipids, total
      cholesterol and total protein, and liver weight were observed at 1.0 mg/kg.
      Histopathology revealed no changes in any organ except for hemorrhage at the
      injection sites. These changes recovered after 4 weeks of withdrawal. Male and
      female squirrel monkeys were given YM866 intravenously for 4 weeks at doses of 0
      (saline), 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. Prolongation of coagulation time
      at the injection site was observed at 0.3 mg/kg or more. Subcutaneous hemorrhage
      and a transient decrease in locomotor activity were observed at 1 mg/kg.
      Prolongation of coagulation time at the injection site was considered to be
      related to the pharmacological action of YM866. The results show that the
      approximate single lethal dose of YM866 is more than 60 mg/kg in rats, and more
      than 10 mg/kg in squirrel monkeys and cynomolgus monkeys. The no-toxic-effect
      level of YM866 after repeated administration for 4 weeks in rats and squirrel
      monkeys is considered to be 0.3 mg/kg.

PMID- 9198010
TI  - Differences in immune responses to a low-molecular compound in three guinea-pig
      strains.
AB  - The present experiments were undertaken to clarify the differences in humoral and
      cellular immune responses to a low-molecular compound, sodium 2,4,6
      trinitrobenznnesul fonate dihydrate (TNBS) in guinea-pig strains. Guinea pigs of
      three different strains, Hartley, Strain 2 and Strain 13, were immunized
      subcutaneously with TNBS (3 mg/body) 2 or 3 times a week, 9 times in total.
      Humoral immune responses to TNBS were assessed by passive cutaneous anaphylaxis
      (PCA) and Arthus reaction, and cellular immune response was assessed by delayed
      type hypersensitivity (DTH). Hartley guinea pigs showed high humoral immune
      responses to TNBS, whereas Strain 2 and 13 guinea pigs showed low responses.
      Strain 2 guinea pigs displayed high cellular immune response to TNBS, and Strain
      13 displayed low cellular immune responses. These results suggest that the
      pattern of humoral immune response to TNBS does not correlate with that of the
      cellular immune responses to TNBS for Strain 2 and Hartley guinea pigs.

PMID- 9198011
TI  - Influence of alkaline ionized water on rat erythrocyte hexokinase activity and
      myocardium.
AB  - Alkaline ionized water (AKW) produced by the electrolysis of tap water (TPW) was
      given to pregnant rats throughout gestation. AKW was subsequently given to
      infants as a test group until 15 weeks old to determine changes in body and organ
      weights, erythrocyte hexokinase (HK) activity and histological preparations of
      myocardiac muscle. The results were compared with those for rats given TPW. Body
      weight of male and female rats given AKWA at 3 to 11 weeks of age after birth
      significantly increased beyond control group values. Organ weights of offspring
      at 15 weeks-old showed no statistical difference for either group. HK activity,
      the rate-determining enzyme in erythrocyte glycolysis, significantly increased in
      males given AKW at 15 weeks-old. This suggests that AKW intake causes elevation
      of metabolic activity. Hyperkalemia was observed in males and females given AKW
      at 15 weeks-old. Especially in males, pathological changes of necrosis in
      myocardiac muscle were observed.

PMID- 9198012
TI  - Nasal lesions induced by intranasal administration of benzaikonium chloride in
      rats.
AB  - We investigated the lesions of nasal cavity mucous membrane caused by
      administration of 0.01, 0.05 and 0.10 w/v% Benzalkonium chloride (BZC) solutions
      in the nasal cavity of rats. No BZC-induced symptoms or nasal lesions were seen
      in the 0.01 w/v% BZC-treated group. On the other hand, BZC-induced symptoms such
      as nasal sound and rubbing the nose with forelegs were observed in the 0.05 and
      0.10 w/v% BZC-treated groups. Additionally, BZC-induced lesions, including
      epithelial desquamation, inflammation and edema, occurred in the anterior nasal
      cavity in the 0.05 and 0.10 w/v% BZC-treated groups, but these lesions were
      confined to the dorsal meatus and the adjacent nasal septum. These results
      indicate that 0.01 w/v% BZC solution has no effect on the nasal cavity mucous
      membrane. However, 0.05 and 0.10 w/v% BZC solutions induce lesions in the nasal
      cavity mucous membrane due to their irritating effect.

PMID- 9198013
TI  - Optimal phosphor thickness for portal imaging.
AB  - A theoretical approach known as quantum accounting diagram (QAD) analysis has
      been used to calculate the spatial-frequency-dependent detective quantum
      efficiency (DQE) of two portal imaging systems: one based on a video camera and
      another based on an amorphous silicon array. The spatial frequency-dependent DQEs
      have then been used to determine indices of displayed and perceived image
      quality. These indices are figures of merit that can be used to optimize the
      design of linear imaging systems. We have used this approach to determine which
      of eight phosphor screen thicknesses (ranging between 67 and 947 mg/cm2) is
      optimal for the two designs of portal imaging systems. The physical
      characteristics (i.e., detection efficiencies, gains, and MTFs) of each of the
      eight x-ray detectors have been measured and combined with the physical
      characteristics of the remaining components to calculate the theoretical DQEs. In
      turn, the DQEs have been used to calculate theoretical indices of displayed and
      perceived image quality for two types of objects: a pelvis object and a pointlike
      object. The maximal indices of displayed and perceived image quality were
      obtained with screen thickness ranging between 358 and 947 mg/cm2, depending upon
      the imaging system design and the object being imaged. Importantly, the results
      showed that there is no single optimal screen thickness. The optimal thickness
      depended upon imaging task (e.g., detecting large, low-contrast structures, or
      detecting edges and small structures). Nevertheless, the results showed that
      there were only modest improvements in the indices of image quality for phosphor
      screens thicker than 350-400 mg/cm2.

PMID- 9198014
TI  - A quantum accounting and detective quantum efficiency analysis for video-based
      portal imaging.
AB  - The quality of images generated with radiographic imaging systems can be degraded
      if an inadequate number of secondary quanta are used at any stage before
      production of the final image. A theoretical technique known as a "quantum
      accounting diagram" (QAD) analysis has been developed recently to predict the
      detective quantum efficiency (DQE) of an imaging system as a function of spatial
      frequency based on an analysis of the propagation of quanta. It is used to
      determine the "quantum sink" stage(s) (stages which degrade the DQE of an imaging
      system due to quantum noise caused by a finite number of quanta), and to suggest
      design improvements to maximize image quality. We have used this QAD analysis to
      evaluate a video-based portal imaging system to determine where changes in design
      will have the most benefit. The system consists of a thick phosphor layer bonded
      to a 1 mm thick copper plate which is viewed by a T.V. camera. The imaging system
      has been modeled as ten cascaded stages, including: (i) conversion of x-ray
      quanta to light quanta; (ii) collection of light by a lens; (iii) detection of
      light quanta by a T.V. camera; (iv) the various blurring processes involved with
      each component of the imaging system; and, (v) addition of noise from the T.V.
      camera. The theoretical DQE obtained with the QAD analysis is in excellent
      agreement with the experimental DQE determined from previously published data. It
      is shown that the DQE is degraded at low spatial frequencies (< 0.25 cycles/mm)
      by quantum sinks both in the number of detected x rays and the number of detected
      optical quanta. At higher spatial frequencies, the optical quantum sink becomes
      the limiting factor in image quality. The secondary quantum sinks can be
      prevented, up to a spatial frequency of 0.5 cycles/mm, by increasing the overall
      system gain by a factor of 9 or more, or by improving the modulation transfer
      function (MTF) of components in the optical chain.

PMID- 9198015
TI  - Intensity-modulated radiotherapy by means of static tomotherapy: a planning and
      verification study.
AB  - There is currently much research interest in developing, evaluating, and
      verifying intensity-modulation techniques. Of particular interest is how well the
      delivery of intensity-modulated profiles can be simulated by planning algorithms,
      and how accurately these profiles can be delivered given the specification
      constraints of linear accelerators. In this paper we present a planning and
      verification study based on delivering radiation in "static-tomotherapy" mode via
      the NOMOS MIMiC (Multileaf intensity-modulation collimator), which sheds some
      light on these issues. An inverse-planning algorithm was used to compute
      intensity-modulated profiles for a 9-coplanar-field plan for a body phantom. The
      algorithm makes several approximations about the form of the elementary fluence
      profile through bixels during delivery. Specifically, it is independent of the
      state of adjacent bixels (i.e., open or closed) and obeys the superposition
      principle. From the standpoint of comparing the predicted versus the delivered
      dose, these assumptions were made irrelevant by a final one-step forward dose
      calculation performed using the optimized intensity profiles. This forward dose
      calculation took into account the penumbral characteristics of the delivery
      system by decomposing the intensity profiles into the set of delivery components.
      Each component was assigned the appropriate penumbral functions thereby ensuring
      that the calculated dose distribution closely predicted the delivered dose
      distribution. The nine intensity modulated fields were delivered to a perspex
      phantom with the same geometry, containing a verification film. In general good
      agreement was found between the predicted and the measured delivered dose
      distributions. All the main features of the predicted dose distribution are seen
      in the delivered. The 90% isodoses were consistently in spatial agreement to
      within 3 mm. At the 50% isodose level consistent spatial agreement was again
      found to within 3 mm, the largest deviation being about 5 mm. The close
      correspondence between the predicted and measured dose distribution demonstrates
      the potential of the MIMiC delivery system. Our results indicate the level of
      dose conformation that is achievable in practice and the accuracy of the dose
      computation algorithm. However, this study only concerned delivery of radiation
      to a 2 cm thick slice, and the dose distribution was only verified in the central
      plane of the phantom where the film was placed. We therefore cannot comment as
      yet on what happens to the dose distribution away from the central film-plane.

PMID- 9198016
TI  - Charged photoparticle production in tissue during radiotherapy.
AB  - Photon-induced proton and alpha particle production in tissue is estimated for
      the photon energy range from 3 to 28 MeV, using the authors' previously
      established methods. It is shown that charged particle emission exceeds neutron
      emission for energies greater than 11 MeV by a factor that reaches a maximum of
      7.0 at 17 MeV. Due to uncertainties in the source data this maximum value should
      be regarded as indicative only. Above 17 MeV the neutron yield rises sharply and
      the ratio of charged particle emission to neutron emission declines to values of
      3.0 and 1.7 at 20 and 28 MeV, respectively.

PMID- 9198017
TI  - Extension of a numerical algorithm to proton dose calculations. I. Comparisons
      with Monte Carlo simulations.
AB  - A numerical algorithm originally developed for electron dose calculations [Med.
      Phys. 21, 1591 (1994)] has been modified for use with proton beams. The algorithm
      recursively propagates the proton distribution in energy, angle, and space from
      one level in an absorbing medium to another at slightly greater depth until all
      protons stop. Vavilov's theory is used to predict, at any point in the absorber,
      the broadening of the primary proton energy-spectrum. Moliere's theory is applied
      to describe the angular distribution, and it is shown that the Gaussian first
      term of Moliere's series expansion is of sufficient accuracy for dose
      calculations. These multiple scattering and energy loss distributions are sampled
      using equal probability spacing to optimize computational speed while maintaining
      calculational accuracy. Inelastic nuclear collisions along the proton
      trajectories are modeled by a simple exponential extinction. Predictions of the
      algorithm for absolute dose deposition by a 160 MeV initially monoenergetic
      proton beam are compared with the results of Monte Carlo simulations performed
      with the PTRAN code. The excellent level of agreement between the results of
      these two methods of dose calculation (< 5% dose and < 3 mm spatial deviations)
      demonstrate that dose deposition from proton beams may be computed to high
      accuracy using this algorithm without the need for extensive empirical
      measurement as input.

PMID- 9198018
TI  - Study of boron neutron capture therapy used neutron source with protons
      bombarding a thick 9Be target.
AB  - Neutron sources created by 4-, 3.5-, and 3-MeV protons striking a thick beryllium
      target were studied via the time-of-flight technique. Protons were accelerated by
      the Peking University 4.5 MV electrostatic accelerator. Two disk-shaped 9Be
      targets with thickness 1.5 and 3 mm were used in the measurements. The time-of
      flight spectra were observed at zero degrees with respect to the incident proton
      beam. The analysis to these time-of-flight spectra is given. The time-of-flight
      spectra were converted to the energy spectra and compared to a neutron spectrum
      of 7Li(p, n)7 Be reaction with incident energy 2.5 MeV, which was also measured
      in this work. Restricted by the spectrometer itself, the threshold of the
      measurements is 400 keV. The results show that by using several MeV protons
      bombarding a thick beryllium target, reactions other than 9Be(p, n)9B produce
      significant contributions to the neutron yield with energy less than 1 MeV.

PMID- 9198019
TI  - An automatic six-degree-of-freedom image registration algorithm for image-guided
      frameless stereotaxic radiosurgery.
AB  - A frameless radiosurgical treatment system has been developed by coupling an
      orthogonal pair of real-time x-ray cameras to a robotically manipulated linear
      accelerator to guide the therapy beam to treatment sites within a patient's
      cranium. The two cameras observe the position and orientation of the patient's
      head in the treatment system coordinate frame. An image registration algorithm
      compares the two real-time radiographs to a corresponding pair of digitally
      synthesized radiographs derived from a CT study of the patient. The algorithm
      determines all six degrees of translational and rotational difference between the
      position of the head in the CT coordinate frame and its position in the treatment
      room coordinate frame. This allows translation of treatment planning coordinates
      into treatment room coordinates without rigidly fixing the patient's head
      position during either the CT scan or treatment. In this paper the image
      registration algorithm is described and measurements of the precision and speed
      with which the process can determine the patient's position are reported. The
      tests have demonstrated translational uncertainty of 0.5-1.0 mm per axis and
      rotational uncertainty of 0.6-1.3 degrees per axis, accomplished in approximately
      2 s elapsed time.

PMID- 9198020
TI  - Transverse tomosynthesis on a digital simulator.
AB  - The availability of digital radiographic imaging on simulators has led to the
      investigation of a number of new imaging possibilities, including digital linear
      tomography (tomosynthesis). It has been shown that a single set of projections in
      this case is sufficient to reconstruct images from multiple planes, including
      planes tilted with respect to the tube motion. The present work examines the
      feasibility of tomosynthetic image reconstruction in transverse planes using a
      CCD-based digital radiotherapy simulator with conventional isocentric rotational
      geometry. General transformation equations were derived to permit image
      reconstruction in arbitrary transverse planes. Transverse images of the skull
      section of the humanoid phantom have been generated using a 360 degrees gantry
      sweep. Bone, air, and radiographic markers are well resolved, but the image
      quality is poor due to the suboptimal scanning geometry available on the
      simulator.

PMID- 9198021
TI  - Plane-parallel ionization chamber response in the buildup region of obliquely
      incident photon beams.
AB  - Fixed-separation plane-parallel ionization chambers have been shown to
      overestimate the dose in the buildup region of normally incident high-energy
      photon beams. This work shows that these ionization chambers exhibit an even
      greater over-response in the buildup region of obliquely incident photon beams.
      This over-response at oblique incidence is greatest at the surface of the phantom
      and increases with increasing angle of beam incidence. In addition, the magnitude
      of the over-response depends on field size, beam energy, and chamber
      construction. This study shows that plane-parallel ionization chambers can over
      respond by more than a factor of 2.3 at the phantom surface for obliquely
      incident high-energy photon fields.

PMID- 9198022
TI  - The effect of dose rate dependence of p-type silicon detectors on linac relative
      dosimetry.
AB  - Cumulative radiation damage to silicon semiconductor diode detectors can induce
      dose rate dependent sensitivity, a concern in the pulsed beam of a linac. Two p
      Si diode photon detectors were used in this study, diodes A and B. Both were
      preirradiated by the supplier to 5 kGy, with diode A receiving an estimated 8 kGy
      from measurements, and diode B, 25 kGy. At 6 MV, the PDD measured with diode B
      was lower (by 4.4% at a depth of 25 cm) than diode A. Using SSD to vary the dose
      per pulse from 0.02 to 0.64 mGy/pulse, diode A was dose rate independent (within
      2%), while the sensitivity of diode B changed by 13%. Silicon diode detectors
      should be checked regularly against ionization chambers in the pulsed beam of a
      linac, especially older high-resistivity diodes that have accumulated dose from
      high-energy photon beams.

PMID- 9198023
TI  - Effective atomic numbers of composite materials for total and partial interaction
      processes for photons, electrons, and protons.
AB  - Effective atomic numbers for total and dominant partial interaction processes of
      photons (1-50 MeV), electrons (1-50 MeV), and protons (1-200 MeV) for the
      composite materials bone (cortical), muscle (striated), water, polystyrene,
      Perspex, and Nylon-6 are derived. For photons, the effective atomic number from
      pair production in the nuclear field is greater than it is from the incoherent
      scattering. For electrons the effective atomic number from the radiative losses
      is greater than it is from the collision losses. In both of these cases however,
      the effective atomic numbers from partial interaction processes remain more or
      less the same, whereas the number from the total interaction increases with
      increasing energy. But in the energy regions from 1 to 5 MeV for photons and from
      1 to 10 MeV for electrons, the number from the total interaction remains
      approximately the same for each of these composite materials. For all these
      materials, in these energy regions the interaction is predominantly with atomic
      electrons and the contributions from the pair production for photons and
      radiative losses for electrons are small. In the case of protons the number from
      total interaction remains more or less the same in the energy region considered.
      In this energy region collisions with atomic electrons dominate, and the
      contribution to the total stopping power is mainly from this process only. Hence
      the derived effective atomic number is basically from the partial process
      involving the interactions with atomic electrons. Thus, for photons from 1 to 5
      MeV for electrons from 1 to 10 MeV and for protons from 1 to 200 MeV, the
      dosimetric data collected with composite tissue equivalent phantoms, designed on
      the basis of interaction with atomic electrons for treatment planning, will have
      less uncertainty.

PMID- 9198024
TI  - The relationship between pixel value and beam quality in photostimulable phosphor
      imaging.
AB  - Direct digital capture systems are relatively new in diagnostic imaging. Full
      utilization of these devices requires a thorough understanding of the image
      formation process. The conversion of x-ray photon energy to a digital pixel value
      in a commercially available photostimulable phosphor (PSP) imaging system is
      investigated in this paper. Pixel values measured at 16 different combinations of
      4 x-ray beam peak voltages (60, 80, 100, and 120 kVp) and 4 beam qualities are
      reported. At 60 and 80 kVp exposures were made at 2.58 x 10(-7) C/kg (1 mR); at
      100 and 120 kVp exposures were made at 5.16 x 10(-7) C/kg (2 mR). Analysis of
      variance was used to determine the statistical significance of the relationship
      between pixel value and beam quality for a given kVp and exposure. A computer
      model accounting for x-ray spectral effects that accurately predicts pixel value
      is presented. Calculated pixel value agree within 5.0% of measured values over
      the range of beam energies, exposures, and qualities.

PMID- 9198025
TI  - The finite-element method for the propagation of light in scattering media:
      frequency domain case.
AB  - A frequency domain light transport model to simulate the transillumination of a
      scattering object with radio frequency intensity modulated light is presented.
      The model is based on the diffusion approximation to the radiative transfer
      equation and uses a finite-element model to allow for complex geometries and an
      inhomogeneous distribution of absorption and scattering. It calculates the
      complex photon density within the object and the complex exitance on the boundary
      of the object. The model is validated against an analytic Green's function model
      for a circular geometry in the homogeneous case, and its accuracy is investigated
      for a range of mesh resolutions, optical parameters, and modulation frequencies.

PMID- 9198026
TI  - False-positive reduction technique for detection of masses on digital mammograms:
      global and local multiresolution texture analysis.
AB  - We investigated the application of multiresolution global and local texture
      features to reduce false-positive detection in a computerized mass detection
      program. One hundred and sixty-eight digitized mammograms were randomly and
      equally divided into training and test groups. From these mammograms, two
      datasets were formed. The first dataset (manual) contained four regions of
      interest (ROIs) selected manually from each of the mammograms. One of the four
      ROIs contained a biopsy-proven mass and the other three contained normal
      parenchyma, including dense, mixed dense/fatty, and fatty tissues. The second
      dataset (hybrid) contained the manually extracted mass ROIs, along with normal
      tissue ROIs extracted by an automated Density-Weighted Contrast Enhancement
      (DWCE) algorithm as false-positive detections. A wavelet transform was used to
      decompose an ROI into several scales. Global texture features were derived from
      the low-pass coefficients in the wavelet transformed images. Local texture
      features were calculated from the suspicious object and the peripheral
      subregions. Linear discriminant models using effective features selected from the
      global, local, or combined feature spaces were established to maximize the
      separation between masses and normal tissue. Receiver Operating Characteristic
      (ROC) analysis was conducted to evaluate the classifier performance. The
      classification accuracy using global features were comparable to that using local
      features. With both global and local features, the average area, Az, under the
      test ROC curve, reached 0.92 for the manual dataset and 0.96 for the hybrid
      dataset, demonstrating statistically significant improvement over those obtained
      with global or local features alone. The results indicated the effectiveness of
      the combined global and local features in the classification of masses and normal
      tissue for false-positive reduction.

PMID- 9198027
TI  - Computerized analysis of interstitial disease in chest radiographs: improvement
      of geometric-pattern feature analysis.
AB  - We have been developing automated computerized schemes to assist radiologists in
      interpreting chest radiographs for interstitial disease based on texture analysis
      and geometric-pattern feature analysis. In this study, we attempted to improve
      the performance of the geometric-pattern feature analysis, because the current
      classification performance with geometric-pattern feature analysis is
      considerably lower than that of texture analysis. In order to improve the
      performance in distinguishing between normal lungs and abnormal lungs with
      interstitial disease, we attempted to remove rib edges in regions of interest
      (ROIs) by using an edge detection technique, and also to reduce false positives
      by using feature analysis techniques. In addition, the effects of many parameters
      on classification performance were investigated to identify proper threshold
      levels, and subsequently the specificity of the geometric-pattern feature
      analysis was improved from 69.5% to 86.1% at a sensitivity of 95.0%. Using a
      combined rule-based method with texture analysis and geometric-pattern feature
      analysis plus the artificial neural network (ANN) method for classification, a
      high specificity of 96.1% was obtained at a sensitivity of 95.0%.

PMID- 9198028
TI  - Theoretical analysis of error propagation in triple-energy absorptiometry:
      application to measurement of lead in bone in vivo.
AB  - We propose a three component tissue decomposition for quantifying lead in bone
      from a mixture of bone and muscle in vivo using a triple-energy absorptiometric
      method. The theoretical optimization of this method, by relating signal
      uncertainty to radiation dose, requires an expression of the signal variance. The
      error propagation was therefore theoretically modeled for a counting detector,
      assuming noise dominance by quantum statistics and neglecting covariance between
      energy levels. A final expression for the lead signal variance at each energy
      level was obtained via a Jacobian matrix. The Jacobian was maximized by choosing
      the first energy as low as permissible by dose constraints below the lead K edge.
      A second optimum was achieved when the upper energy was just above and the middle
      energy was just below the lead K edge. While the signal-to-noise ratio (SNR) had
      similar behavior to that of the Jacobian as a function of middle and upper
      energies, the SNR was almost constant as a function of lower energy in the 40-60
      keV range. Hence, dose could be reduced without SNR loss. A simulated clinical
      measurement on an adult tibia using a 50 mCi 155Eu source and a 10 min
      acquisition time resulted in a standard deviation of 4 micrograms Pb/g bone mass.
      This approach can be applied to other systems containing three components,
      provided there is a K edge within the counting energy range.

PMID- 9198029
TI  - Autosomal dominant polycystic kidney disease: neoplasia in disguise?

PMID- 9198030
TI  - Nephrotoxicity of ifosfamide--moving towards understanding the molecular
      mechanisms.

PMID- 9198031
TI  - Ageing and the renin-angiotensin system.

PMID- 9198032
TI  - Antihypertensive treatment in nephropathy of type II diabetes: role of the
      pharmacological blockade of the renin-angiotensin system.

PMID- 9198033
TI  - I/D polymorphism of the angiotensin converting enzyme gene: a clue to the
      heterogeneity in the progression of renal disease and in the renal response to
      therapy?

PMID- 9198034
TI  - Pancreas transplantation: where do we stand in Europe in 1997?

PMID- 9198035
TI  - How to keep the dialysis patients normotensive? What is the secret of Tassin?

PMID- 9198036
TI  - Renal replacement therapy in an era of socioeconomic changes--report from the
      Polish Registry.

PMID- 9198037
TI  - Intrinsic renal cells are the major source of interleukin-1 beta synthesis in
      normal and diseased rat kidney.
AB  - BACKGROUND: A number of studies have demonstrated a pathological role for
      interleukin-1 (IL-1) in experimental models of glomerulonephritis, but the
      cellular pattern of renal IL-1 production remains poorly characterized. The aim
      of this study, therefore, was to identify the cell types expressing IL-1 in
      normal and diseased rat kidney. METHODS: Renal IL-1 beta expression was examined
      in normal rats and during a 21-day time course of rat accelerated anti-GBM
      glomerulonephritis by northern blotting, in situ hybridization and double
      immunohistochemistry. RESULTS: Interleukin-1 beta mRNA expression was readily
      detectable in normal rat kidney by northern blot analysis and in situ
      hybridization. Immunohistochemistry staining demonstrated constitutive IL-1 beta
      expression by glomerular endothelial cells and cortical tubular epithelial cells.
      There was a marked increase in whole kidney IL-1 beta mRNA in rat anti-GBM
      glomerulonephritis. Glomerular IL-1 beta immunostaining was upregulated, being
      expressed by podocytes, mesangial cells and infiltrating macrophages, and was
      particularly prominent within glomerular crescents. Double staining with the ED1
      antibody showed IL-1 beta expression in up to 13% of glomerular macrophages,
      whereas 48% of macrophages within crescents stained for IL-1 beta. However, the
      most marked increase in IL-1 beta expression was seen in cortical tubular
      epithelial cells, particularly in areas of tubular damage. In situ hybridization
      confirmed that tubular IL-1 beta staining was due to local cytokine synthesis
      rather than protein absorption. CONCLUSIONS: This study has identified
      constitutive IL-1 beta expression by glomerular endothelium and tubular
      epithelial cells in normal rat kidney. In addition, the marked upregulation of IL
      1 beta expression by intrinsic glomerular cells and tubules in rat anti-GBM
      disease suggests an important role for these cells in IL-1 dependent crescent
      formation and tubulointerstitial injury.

PMID- 9198038
TI  - D-penicillamine reduces renal injury in the remnant model of chronic renal
      failure in the rat.
AB  - BACKGROUND: Glomerulosclerosis and interstitial fibrosis, which are cardinal
      features of the end-stage kidney, result from accumulation of extracellular
      matrix proteins, particularly collagen, in the glomerular mesangium and renal
      interstitium. This study examined the effect of D-penicillamine (DPC), which
      inhibits collagen deposition, on disease progression in the remnant kidney.
      METHODS: Two groups of 10 rats underwent two-thirds nephrectomy and were pair-fed
      20% casein paste (Gp 1) or the same paste supplemented with 90 mg/kg body wt per
      day of DPC (Gp 2). Two further groups of five non-nephrectomized animals also
      received 20% casein paste either alone (Gp 3) or supplemented with DPC (Gp 4). In
      a further experiment, systolic blood pressure was compared at 1 and 4 weeks after
      nephrectomy in eight DPC-treated remnants and eight untreated controls. RESULTS:
      Gp 2 developed significantly less proteinuria than Gp 1 (41 +/- 9 vs 142 +/- 33
      mg/24 h at 6 weeks, P < 0.005; 136 +/- 36 vs 282 +/- 59 mg/24 h at 12 weeks, P <
      0.05). At sacrifice after 12 weeks, glomerular filtration rates were higher (1.34
      +/- 0.08 vs 1.07 +/- 0.1 ml/min, P < 0.05), kidney total collagen content was
      lower (14.9 +/- 1.5 vs 26.9 +/- 5.4 mg/kidney, P < 0.05) and glomerular
      abnormalities, interstitial fibrosis and lymphocytic infiltration were less
      marked in Gp 2 compared with Gp 1. DPC had no effect on protein excretion, total
      kidney collagen or GFR in non-nephrectomized rats, and did not influence the
      early rise in blood pressure seen after two-thirds nephrectomy. CONCLUSIONS:
      These findings demonstrate that DPC reduces renal injury in the remnant kidney,
      and raise the possibility of a therapeutic role for DPC in the treatment of
      patients with chronic renal failure.

PMID- 9198039
TI  - Expression of cell adhesion molecules in primary renal disease and renal
      allograft rejection.
AB  - BACKGROUND: In vitro studies have demonstrated that inflammatory mediators such
      as the cytokines TNF alpha and IL-1 upregulate or induce de novo expression of
      cell adhesion molecules on endothelial and epithelial cells. In the present study
      the expression of the cell adhesion molecules ICAM-1, VCAM-1, E-selectin and
      PECAM-1 was investigated in renal biopsies from patients with primary renal
      diseases (n = 66) and from renal allograft recipients (n = 42). METHODS:
      Expression of the cell adhesion molecules was determined by immunohistochemistry
      of frozen sections using monoclonal antibodies directed against PECAM-1, ICAM-1,
      VCAM-1, E-selectin and MHC class II molecules (APAAP method). RESULTS AND
      CONCLUSIONS: PECAM-1 and ICAM-1 were expressed in the renal vasculature and
      disappeared in obliterated glomeruli with endothelial cell destruction. ICAM-1
      but not PECAM-1 was upregulated in renal endothelia in acute allograft rejection
      and inflammatory primary renal diseases. Tubular de novo expression of ICAM-1 and
      VCAM-1 correlated with severe structural damage of the renal parenchyma including
      interstitial fibrosis. Vascular and/or glomerular VCAM-1 and E-selectin
      expression was pronounced in severe acute allograft rejection and also reflected
      the intensity of inflammatory reactions in primary renal diseases with or without
      autoimmune disorders. De novo expression of VCAM-1 and E-selectin in renal
      vessels and/or glomeruli and overexpression of ICAM-1 are markers of acute and
      severe inflammatory processes in biopsies from allograft recipients and patients
      with primary renal diseases.

PMID- 9198040
TI  - Von Hippel-Lindau disease: an important differential diagnosis of polycystic
      kidney disease.
AB  - Von Hippel Lindau disease is a dominantly inherited familial cancer syndrome,
      characterized by retinal, spinal, and cerebellar haemangioblastomas, renal cell
      carcinomas, and phaeochromocytomas. Cysts of the kidney and pancreas may also
      occur. We describe a large three-generation Irish family with VHL disease who
      initially presented with features typical of autosomal dominant polycystic kidney
      disease. Eight clinically affected individuals were found. Visceral complications
      were particularly prominent within the family. There were no cases of retinal
      angiomata or phaeochromocytoma. The diagnosis was confirmed by genetic linkage
      analysis in this family, although the exact mutation has yet to be defined.

PMID- 9198041
TI  - Expression of beta 1 integrins in IgA nephropathy.
AB  - AIM: To compare the expression of beta 1 integrins in renal biopsies from
      patients with IgA nephropathy with that found in normal human kidney. METHODS:
      Thirty renal biopsies from patients with IgA disease plus six control specimens
      were stained with monoclonal antibodies directed against the alpha 1, alpha 2,
      alpha 3, alpha 4, alpha 5, alpha 6, alpha v, and beta 1 integrin chains using the
      alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The intensity
      of integrin expression was graded semiquantitatively by a pathologist unaware of
      the antibody used. RESULTS: Glomerular crescents stained strongly for alpha 3,
      alpha v, and beta 1, but integrin expression was greatly reduced or absent in
      fibrotic glomeruli. There were no alterations in the intensity of mesangial cell
      staining for any of the integrins tested. There was accentuated staining for the
      alpha 2, alpha 5, alpha v, and beta 1 chains in areas of interstitial scarring
      plus alpha 2, alpha 3, alpha v, and beta 1 on damaged tubules. Inflammatory cells
      expressed alpha 4, alpha 5, and beta 1. CONCLUSIONS: In IgA nephropathy the
      interstitium is the main site of altered beta 1 integrin expression. Glomerular
      crescents also express several beta 1 integrins, but we found no differences in
      the intensity of integrin expression on mesangial cells. Altered beta 1 integrin
      expression may play a role in tubulointerstitial scarring in IgA disease. Thus
      modulation of integrin expression might attenuate this process.

PMID- 9198042
TI  - The clinical spectrum of shunt nephritis.
AB  - BACKGROUND: Shunt nephritis is an immune-complex-mediated glomerulonephritis (GN)
      associated with chronically infected ventriculoatrial shunts inserted for
      treatment of hydrocephalus. METHODS: Six patients aged 5-22 years with shunt
      nephritis are reported who have been observed between 1971 and 1994. The clinical
      course and long-term outcome are analysed in relation to the time of diagnosis
      and renal histopathology. RESULTS: The time of diagnosis of shunt nephritis
      ranged from 0.3 to 4.5 years after the last shunt operation. Diagnosis was
      delayed up to 1.5 years after the first clinical manifestations. All patients had
      signs of infection, i.e. recurrent fever, hepatosplenomegaly, anaemia, and
      cerebral symptoms. Renal manifestations consisted of haematuria (macroscopic in 3
      patients), proteinuria (heavy in 5), renal insufficiency (4) and hypertension
      (2). Decreased C3 levels, cryoglobulins, and antinuclear factors were frequent.
      Cultures of blood and cerebrospinal fluid provided growth mainly of S.
      epidermidis. Renal biopsy revealed endocapillary GN (1), membranoproliferative GN
      (1) and endocapillary/extracapillary GN with crescents (2). All patients received
      antibiotics i.v. Complete recovery was observed in three of four patients in whom
      the shunt was totally removed, supported by transient external drainage of
      cerebrospinal fluid, and followed by placement of a ventriculoperitoneal shunt.
      One child with delayed diagnosis, presenting with a serum creatinine of 3.2
      mg/dl, hypertension, and severe scarring on renal biopsy, rapidly progressed to
      irreversible ESRD within 5 months. Two patients without and only partial removal
      of the shunt died subsequently from sepsis. CONCLUSIONS: The renal outcome of
      shunt nephritis is good if early diagnosis and treatment is provided including
      i.v. antibiotics and total removal of the infected shunt. The possible
      progression to ESRD requires frequent nephrological monitoring of patients with
      ventriculoatrial shunts.

PMID- 9198043
TI  - Decreasing glomerular filtration rate--an indicator of more advanced diabetic
      glomerulopathy in the early course of microalbuminuria in IDDM adolescents?
AB  - BACKGROUND: Overt diabetic nephropathy is accompanied by a progressive decline in
      glomerular filtration rate (GFR). In this study we have investigated if a
      reduction of GFR already during the transition from normo- to microalbuminuria is
      associated with glomerular structural changes. METHODS: Seventeen adolescents (11
      girls/6 boys) with 10.5 (3.3) (mean, SD) years of IDDM were studied. GFR was
      previously measured in the normoalbuminuric stage 2-5 years prior to the renal
      biopsy, and measured again at the time for the biopsy, after in mean 1.8 years of
      microalbuminuria (15-200 micrograms/min). HbAlc and albumin excretion rate were
      measured 3 or 4 times yearly and blood pressure 1-4 times yearly between the GFR
      examinations. The associations between the yearly rate of fall in GFR and
      basement membrane (BM) thickness, mesangial and matrix volume fractions, matrix
      star volume, mean capillary diameter (CAPD), area of filtration surface
      (peripheral BM) per glomerulus, total capillary length per glomerulus, the ratio
      of peripheral BM to capillary surface, glomerular volume, and interstitial volume
      fraction were analysed. RESULTS: BM thickness and matrix star volume were
      increased in patients with, as compared to those without, a decline in GFR > or =
      6 ml/min per year (P < 0.005 respectively). Patients with previous glomerular
      hyperfiltration (> or = 135 ml/min per 1.73 m2) showed the steepest decline in
      GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering
      patients, P < 0.001. The rate of fall in GFR was positively correlated to BM
      thickness (P < 0.001), interstitial volume fraction (P = 0.02) and CAPD (P =
      0.04), mean HbAlc (P = 0.01), but not to the change in HbAlc between GFR
      examinations. CONCLUSION: A decreasing glomerular filtration rate in the early
      stage of microalbuminuria may be due to more advanced diabetic glomerulopathy
      than in IDDM patients with stable GFR.

PMID- 9198044
TI  - Is endogenous erythropoietin a pathogenetic factor in the development of
      essential hypertension?
AB  - BACKGROUND: Recent experimental studies have found that erythropoietin elicits
      vasoconstriction and proliferation of endothelial cells. We conducted the
      following study to assess the possible interactions between endogenous
      erythropoietin, systemic and renal haemodynamics at different stages of essential
      hypertension. METHODS: We examined 47 patients with borderline essential
      hypertension (age 26 +/- 3 years) and 49 patients with established essential
      hypertension WHO stage I-II (age 52 +/- 10 years), and compared them to 42
      normotensive individuals (age 26 +/- 3 years). The concentration of
      erythropoietin (radioimmunoassay), 24-h ambulatory blood pressure (Spacelab
      90207), systemic haemodynamics (Doppler sonography) and renal haemodynamics (para
      aminohippuric acid and inulin clearance) were determined. RESULTS: Erythropoietin
      was within normal range and similar among the three groups. In patients with
      established essential hypertension, a close correlation was found between
      erythropoietin and systolic (r = 0.45, P < 0.002) and diastolic (r = 0.51, P <
      0.001) ambulatory blood pressure. In contrast, ambulatory blood pressure was not
      correlated with erythropoietin in subjects with borderline hypertension. Total
      peripheral resistance (r = 0.41, P < 0.02) was linked to erythropoietin in
      established but not in borderline hypertension. However, erythropoietin was
      inversely correlated with renal plasma flow in both established and borderline
      hypertension (r = -0.33, P < 0.05, and r = -0.34, P < 0.05 respectively). In
      normotensive subjects, in contrast, erythropoietin was not correlated with any of
      the determined variables. In neither group erythropoietin was linked to the
      haematocrit or hemoglobin concentration. CONCLUSION: The correlation between
      erythropoietin and renal vascular changes which is already present in borderline
      hypertension and is confirmed in established hypertension indicates an
      involvement of erythropoietin in the development of essential hypertension. The
      presence of normal concentrations of endogenous erythropoietin in all groups
      suggests a dysregulation of erythropoietin in patients with essential
      hypertension as the pathophysiological link between erythropoietin and vascular
      changes.

PMID- 9198045
TI  - Decreased excretion of urine glycosaminoglycans as marker in renal amyloidosis.
AB  - BACKGROUND: The diagnosis of renal amyloidosis is normally established by kidney
      biopsy. In order to advance the determination of the diagnosis and the initiation
      of the therapy, fast and cheap, non-invasive diagnostic techniques are required.
      METHODS: Urine excretion of glycosaminoglycans (GAG) was measured in 10 patients
      with AA amyloidosis and 5 patients with AL amyloidosis and compared to 25
      controls with primary glomerular diseases and 22 healthy controls. The subjects
      with primary glomerular disease were matched with regard to their renal function
      and the degree of albuminuria. RESULTS: The median urine GAG to creatinine ratio
      and the median fractional GAG excretion were significantly decreased (P < 0.05)
      in both AA amyloidosis (0.21 mg/mmol and 0.053 respectively) and AL amyloidosis
      (0.33 mg/mmol and 0.077 respectively) compared to control patients with primary
      glomerular disease (1.73 mg/mmol and 0.336 respectively) and healthy controls
      (2.67 mg/mmol and 0.226 respectively). The urine GAG to creatinine ratio did not
      correlate to age, sex, serum creatinine, urine albumin, or to the plasma levels
      of acute phase proteins. CONCLUSIONS: The decreased GAG excretion in renal
      amyloidosis is probably caused both by diminished number of functioning nephrons,
      decreased GAG synthesis in functioning glomeruli, and the trapping of GAG by
      amyloid fibrils. Urinary GAG excretion may serve as an independent marker of
      renal amyloidosis. It may be used in diagnostic work-up of renal amyloidosis in
      patients with glomerular diseases and in screening of amyloidosis in patients
      with chronic inflammatory disorders, with or without signs of renal disease.

PMID- 9198046
TI  - Enhanced gene expression of scavenger receptor in peripheral blood monocytes from
      patients on cuprophane haemodialysis.
AB  - BACKGROUND: Macrophage scavenger receptor (SR) is implicated in playing a key
      role in macrophage-derived foam cell formation by taking up a large amount of
      modified low-density lipoproteins (LDL). It has also been postulated that alpha 2
      macroglobulin receptor/LDL receptor-related protein (alpha 2MG/LRP) is involved
      in the development of foam cells by taking up apo E-enriched chylomicrons and
      VLDL remnants, and lipoprotein lipase-triglyceride-rich lipoprotein complexes.
      Accumulation of these lipid-loaded monocyte/ macrophages in the subendothelial
      space is considered to be an early event of atherogenesis. Since atherogenesis is
      considered to be accelerated in dialysis patients, we attempted to investigate
      whether gene expression of SR and alpha 2MG/LRP are altered in peripheral blood
      monocytes from patients on haemodialysis with a cuprophane (Cu) or
      polymethylmethacrylate (PMMA) membranes. METHODS: Peripheral blood monocytes
      (PBM) were prepared from patients undergoing haemodialysis with a Cu membrane (n
      = 9), patients undergoing haemodialysis with a PMMA membrane (n = 9), and healthy
      controls (n = 7). In a separate experiment we examined SR gene expression in
      uraemic patients (n = 12) and healthy controls (n = 9). SR and alpha 2MG/LRP mRNA
      were semiquantitated using reverse-transcription polymerase chain reaction (RT
      PCR) assay followed by Southern blotting. RESULTS: SR mRNA expression in PBM from
      patients on chronic haemodialysis with a Cu membrane was about twofold higher
      than that in PBM from patients on chronic haemodialysis with a PMMA membrane or
      the controls (P < 0.05). alpha 2MG/LRP mRNA expression in PBM showed no
      difference among these, three groups. SR gene expression in monocytes from
      uraemic patients was not increased compared with that in the controls.
      CONCLUSION: PBM from patients under Cu membrane dialysis showed higher gene
      expression of SR than patients under PMMA membrane dialysis, uraemic patients, or
      healthy controls. This increased gene expression of SR in monocytes may be
      associated with the pathogenesis of accelerated atherosclerosis in patients on
      dialysis with a Cu membrane.

PMID- 9198048
TI  - Comparison of high-efficiency and standard haemodialysis providing equal urea
      clearances by partial and total dialysate quantification.
AB  - BACKGROUND: Short-duration high-efficiency haemodialysis has been utilized
      increasingly in recent years to deliver adequate blood urea clearances per
      dialysis session. However, high-efficiency and standard-duration haemodialysis
      schedules, which achieve equal patient urea clearances, may not represent
      equivalent dialytic therapy due to solute differences in intercompartmental
      dysequilibrium during dialysis and differences in dialysis mechanics. METHODS: To
      circumvent the effects of intercompartmental dysequilibrium and postdialysis
      rebound solute clearances were measured by direct dialysis quantification (total
      and partial dialysate collections) rather than blood clearances. High-efficiency
      haemodialysis (dialyser blood flow rate = 400 ml/min; dialysis time = 170.67 min)
      was compared with standard haemodialysis (dialyser blood flow rate = 200 ml/min;
      dialysis time = 240 min) performed in random order in six anuric patients using
      Fresenius F8 dialysers and the same haemodialysis machine. Such haemodialysis
      schedules were prescribed to provide equivalent urea clearances. RESULTS: Patient
      plasma water urea clearances measured by direct dialysis quantification were
      equivalent, whereas high efficiency haemodialysis achieved significantly lower
      phosphate clearances (P = 0.01), less net bicarbonate absorption (P = 0.01), and
      lower beta 2 microglobulin removal (P < 0.001) than standard haemodialysis.
      Estimated total dialysate effluent volumes with partial dialysate collection and
      total dialysate collection correlated closely (r = 0.95) and there were no
      differences between patient urea, creatinine and phosphate clearances measured by
      partial and total dialysate quantification. CONCLUSIONS: The data indicate that
      even if high-efficiency and standard haemodialysis provide equal whole-body urea
      clearances, delivered dialysis therapy is not equivalent. The partial dialysate
      collection method is as accurate as the cumbersome total dialysate collection
      approach and may be applied to assess delivered dialysis dose by minor
      modification of current haemodialysis machines.

PMID- 9198047
TI  - Percentage of hypochromic red blood cells as predictor of erythropoietic and iron
      response after i.v. iron supplementation in maintenance haemodialysis patients.
AB  - BACKGROUND: The percentage of hypochromic red blood cells (RBC), defined as those
      with a cellular haemoglobin < 28 g/dl has been suggested to be a sensitive marker
      of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus,
      during rHuEpo therapy an increase in hypochromic RBC to > 10% would indicate that
      more intensive iron supplementation may be required. METHODS: We investigated 70
      HD patients 57.1 +/- 15.3 years old and on maintenance HD for 66.3 +/- 47.9
      months without blood loss from gastrointestinal bleeding or from the vascular
      access, without surgery and without infectious disease or malignancy. During the
      study period of 12 weeks, each patient received in i.v. dose of 800 mg
      ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC
      were measured before and every 4 weeks after the start of the study; serum
      ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at
      the beginning (baseline) and end of the study. RESULTS: At baseline the
      percentage of hypochromic RBC was < or = 5.0% in 28 patients, > 5.0 and < or =
      10.0% in 25 patients and > 10.0% in 17 patients, suggesting functional iron
      deficiency in at least 42 patients. Nine patients had serum ferritin values < 100
      micrograms/1; nonetheless in these patients the median percentage of hypochromic
      RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can
      occur in the presence of normal amounts of hypochromic RBC. There was a
      significant correlation between serum ferritin levels and hypochromic RBC at the
      end, but not at the beginning, of the study. However, there was no correlation
      between ZPP and hypochromic RBC at any time during the study. During i.v. iron
      supplementation the rHuEpo dose could be reduced by 8.5% in patients with
      hypochromic RBC < or = 5.0%, by 11.3% in patients with hypochromic RBC > 5.0 and
      < or = 10.0% and by 23.4% in patients with hypochromic RBC > 10.0%, demonstrating
      the benefit of i.v. iron in patients with functional iron deficiency. In HD
      patients in whom serum ferritin levels remained below 290 micrograms/l until the
      end of the study, a significant reduction of the rHuEpo dosage could be obtained
      during i.v. iron therapy. This was not the case in patients with serum ferritin >
      290 micrograms/l after iron supplementation. We found that the percentage of
      hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness
      in CRP-positive patients. HD patients with hypochromic RBC > 6% and low to
      moderate increases in serum ferritin levels after i.v. iron supplementation
      significantly benefit from i.v. iron therapy compared to HD patients with
      hypochromic RBC < 6%. CONCLUSIONS: Two different aspects should be taken into
      consideration in HD patients treated with rHuEpo and concomitant i.v. iron
      therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate
      delivery of the supplemented iron to the erythropoietic system. The patient's
      percentage of hypochromic RBC and increase in serum ferritin after i.v. iron
      supplementation should be used to decide whether or not i.v. iron should be given
      and to monitor this type of therapy in HD patients.

PMID- 9198049
TI  - Relevance of conventional cardiovascular risk factors for the prediction of
      coronary artery disease in diabetic patients on renal replacement therapy.
AB  - BACKGROUND: Diabetic patients undergoing renal replacement therapy have a high
      cardiovascular mortality. As the rate of patients with diabetic nephropathy
      rises, adequate risk stratification subsequent to renal transplantation is
      warranted. It was the aim of our study to elucidate whether conventional risk
      factors are valid predictors of coronary artery disease in this group of patients
      with chronic renal failure subsequent to transplantation. METHODS AND RESULTS:
      Between 1989 and 1993, 105 consecutive diabetic patients (70 men, 35 women, 77
      type I and 28 type II diabetics, mean age 43 +/- 12 years) were examined during
      the first six months of dialysis treatment. Coronary angiography was performed in
      all patients regardless of clinical symptoms of coronary artery disease (CAD). In
      38 patients (36%) CAD was documented (single-vessel disease: 17 patients, double
      vessel disease: 6 patients, triple-vessel disease: 15 patients). Manifestations
      of coronary atherosclerosis were seen in 49 patients (47%). Angina pectoris was
      present in 9 out of 38 patients (24%), the sensitivity to detect CAD was 43% and
      52% for ST-segment depression assessed at rest. Risk factors for atherosclerosis
      like hypertension, smoking, cholesterol (total cholesterol, HDL-,LDL
      cholesterol), triglycerides as well as concentrations of lipoprotein (a) and
      fibrinogen were not significantly different in patients with or without coronary
      artery disease. Atherosclerotic manifestations of cerebral and peripheral
      arteries as well as manifestations of diabetic microangiopathy like retinopathy
      did not correlate with the prevalence of CAD. In 11 out of 38 patients (29%)
      cardiac interventions (3 x CA BG, 8 x PTCA) were performed. All of them were
      defined as transplantable after myocardial revascularisation. CONCLUSIONS:
      Clinical symptoms as well as the cardiovascular risk profile are not valid
      predictors of CAD in diabetic patients with chronic renal failure. Therefore
      coronary angiography should be performed in all diabetic patients prior to renal
      transplantation.

PMID- 9198050
TI  - Monomeric and dimeric beta 2-microglobulin may be extracted from amyloid deposits
      in vitro.
AB  - BACKGROUND: There is a controversy as to whether beta 2-microglobulin (beta 2M
      amyloid deposits may be degraded resulting in regression and cure of amyloidosis.
      We have recently reported a long-term clinical study involving transplanted
      patients suggesting that there is no resorption of amyloid deposits in vivo, even
      after correction of the primary cause of amyloidosis. To progress in the study of
      the solubility of amyloid fibrils we performed an in vitro study with the intent
      to remove protein constituents from amyloid fibrils and amyloid deposits.
      METHODS: Amyloid fibrils were prepurified from three amyloid deposits surgically
      obtained from carpal tunnel. They were incubated for 2 h with a phosphate
      buffered saline (PBS) solution containing trypsin, collagenase, kallikrein, the
      three of them, or PBS alone. The experiments were repeated in the presence of the
      antiprotease alpha 2 macroglobulin (alpha 2M). RESULTS: Several bands were
      observed when the supernatants were run through SDS-PAGE. Western blotting
      identified in these bands the presence of alpha 2M, light chains of
      immunoglobulins and beta 2M in mono- and dimeric form. The same proteins were
      solubilized with PBS alone. Equivalent results were obtained with crude amyloid
      deposits; however, beta 2M presented almost exclusively in monomeric form.
      CONCLUSIONS: These results show that the protein constituents may be recovered
      from amyloid fibrils in vitro. They also show that even the more insoluble beta
      2M dimers are resuspended by the action of PBS, with no need for proteases to
      cleave their attachment to the amyloid deposits.

PMID- 9198051
TI  - High prevalence and usual persistence of serum monoclonal immunoglobulins
      evidenced by sensitive methods in renal transplant recipients.
AB  - BACKGROUND: The occurrence of serum monoclonal immunoglobulins in kidney
      transplant recipients is well known but their significance and predictive value
      for the occurrence of lymphoma are a matter of debate. We therefore conducted a
      study of monoclonal immunoglobulins by a sensitive method during the long-term
      follow up of grafted patients. METHODS: Monoclonal immunoglobulins were
      characterized by high-resolution electrophoresis, conventional
      immunoelectrophoretic analysis, and a sensitive Western blotting procedure in the
      serum from 84 renal transplant recipients prior to grafting and subsequently,
      with a 1-8-year follow-up and excluding the patients who developed posttransplant
      lymphoma. RESULTS: Low abundance monoclonal immunoglobulins were detectable prior
      to transplantation in 56 cases (66.6%) and after graft in 72 cases (85.5%) (and
      in 1 case (1.2%) and 18 cases (21.4%) of cases respectively, by
      immunoelectrophoresis). These abnormalities were often multiple in individual
      sera. Monoclonal components detected by immunoblotting were transient in 23.8% of
      patients only (whereas those evidenced by immunoelectrophoresis usually became
      undetectable by this method) and their pattern was remarkably stable in the
      majority of cases. The frequency of post-transplant monoclonal immunoglobulins
      was higher in patients of more than 50 years of age than in younger patients. The
      appearance of monoclonal components after grafting and their transient character
      correlated with CMV infections. No correlation was found with various other
      parameters. The isotypic distribution of monoclonal immunoglobulins with an IgM,
      IgG3, and IgG1 predominance and an abnormally low kappa/lambda ratio was the same
      as that observed in various immunodeficiency states. The monoclonal
      immunoglobulin pattern in three further patients who developed post-transplant
      lymphoma was unremarkable. CONCLUSION: Monoclonal immunoglobulins hence are not
      discriminant for lymphoma and their characterization does not appear to be
      necessary in the evaluation of followed up grafted patients, at least for a
      prediction of post-transplant lymphoma.

PMID- 9198052
TI  - Intradermal versus intramuscular hepatitis b re-vaccination in non-responsive
      chronic dialysis patients: a prospective randomized study with cost-effectiveness
      evaluation.
AB  - BACKGROUND: It has been calculated that 30% of chronic uraemic patients fail to
      produce antibodies to HBsAg antigen after hepatitis B (HB) vaccination. Low-dose
      intradermal (i.d.) inoculations and supplementary intramuscular (i.m.) injections
      have been reported to improve the response rate in previous non-responder chronic
      uraemic patients, but no cost-effectiveness evaluations have been made about this
      issue. METHODS: We re-vaccinated 50 chronic dialysis patients, who did not have
      any detectable anti-HBs antibody after a reinforced protocol of hepatitis B
      vaccine given by i.m. route, with hepatitis B recombinant DNA yeast vaccine (80
      micrograms) by intradermal (25 patients) or intramuscular (25 patients)
      administration (randomly allocated). We used the same amount of HBsAg in order to
      exclude the confounding effect of the dose level administered on the immune
      response of uraemic patients. We studied, over a 20-month follow-up, the
      persistence of anti-HBs antibodies in our responder vaccinees. We made a
      comparison between the costs of our re-vaccination protocol and the other re
      vaccination strategies that have been recently suggested. RESULTS: One month
      after completion of re-vaccination protocol, seroconversion rates (100% vs 48%, P
      = 0.008) and proportion of patients who elicited protective anti-HBs titres (96%
      vs 40%, P = 0.0001) were significantly higher in i.d. compared to i.m. patients.
      The levels of anti-HBs expressed as geometric mean titres and 95% confidence
      intervals (GMT (95% CI)), were significantly increased in i.d. than in i.m.
      groups, 100 (44-187) vs 26 (14-52) mUI/ml (P = 0.018). At month 12, the
      seroconversion rates were 57 vs 14% in i.d. and i.m. groups respectively (P =
      0.158); the seroprotection rate was higher in i.d. individuals in comparison with
      i.m. patients, 50 vs 0%, P = 0.072. At month 20, the seroconversion rates were 54
      and 0% among i.d. and i.m. patients respectively (P = 0.055); the seroprotection
      rate was higher in i.d. than in i.m. group (30 vs 0%, P = 0.2). At month 20, the
      median anti-HBs titres in i.d. patients were 21 mUI/ml, and GMT (95% CI) were
      20.9 (2-54) mUI/ml. No important general or local side-effects were observed. The
      cost of our schedule was $92 US whereas the costs of other re-vaccination
      protocols ranged between 138 and $807 US. CONCLUSIONS: Our results show that the
      unresponsiveness to recombinant yeast-derived vaccine may be mostly reversed by
      repeated low-dose i.d. injections of the same agent. In spite of an equal amount
      of HBsAg received, i.d. hepatitis B re-vaccination shows higher immunogenicity
      compared to i.m. administration over a 20-month observation period. Cost
      effectiveness analysis demonstrated that the intradermal administration of HB
      vaccine is the most clinically effective re-vaccination strategy; it is also the
      most unexpensive one. We strongly recommend low-dose intradermal inoculations in
      order to re-vaccinate chronic dialysis patients who fail to respond to hepatitis
      B vaccination.

PMID- 9198053
TI  - Comparison of lactate and bicarbonate buffered haemofiltration fluids: use in
      critically ill patients.
AB  - OBJECTIVE: To compare acid-base balance, lactate concentration, and haemodynamic
      and O2 transport variables during haemofiltration with replacement fluid
      containing 44.5 mmol/l Na+ lactate or 40 mmol/l Na+ HCO3- and 3 mmol/l lactic
      acid. DESIGN: A prospective, randomized trial. SETTING: A multidisciplinary,
      adult intensive care unit in a university hospital. PATIENTS: Forty acidotic
      patients who required haemofiltration, were dependent on mechanical ventilation,
      and had PA catheters in situ. INTERVENTIONS: During haemofiltration patients
      received lactate or bicarbonate replacement fluid at a mean rate of 1.7 l/h (SD
      0.3). Arterial blood gases, plasma lactate, and haemodynamic and O2 transport
      variables were measured before and after 12 and 24 h haemofiltration.
      Ultrafiltrate was collected for lactate estimation. MEASUREMENTS AND MAIN
      RESULTS: As means (SD). The net gain of lactate was 63 mmol/h (12 mmol) with Na+
      lactate and 0 mmol/h (0.3 mmol) with Na+ HCO3-. There was a significant increase
      in pH and [lactate] in both groups, but [lactate] was higher in patients
      receiving lactate. Twenty-one patients survived to ICU discharge, these patients
      were significantly less acidotic after filtration (lactate group: 0 h: pH 7.23
      (0.09), [lactate] 2.4 mmol/l (1.7); 12 h: pH 7.34 (0.09), [lactate] 4.7 mmol/l
      (2.4); 24 h: pH 7.36 (0.07), [lactate] 4.7 mmol (2.7). HCO3 group: 0 h: pH 7.23
      (0.09), [lactate] 2.3 (1.3); 12 h: pH 7.32 (0.06), [lactate] 2.9 mmol/l (1.8); 24
      h: pH 7.35 (0.08), [lactate] 2.8 mmol/l (2.0). Base deficit: survivors: 0 h: 9
      mmol/l (4); 12 h: 2 mmol/l (3). Non-survivors: 0 h: 10 mmol/l (3); 12 h: 6 mmol/l
      (3)). Haemodynamic and O2 transport variables were not significantly affected by
      treatment group or outcome. CONCLUSIONS: The degree of correction of acidosis
      during the first 24 h of haemofiltration was determined by patients outcome but
      was not affected by the substitution of bicarbonate- for lactate-containing
      replacement fluids.

PMID- 9198054
TI  - Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal
      dialysis.
AB  - BACKGROUND: The surface-active substance dioctyl sodium sulphosuccinate (DSS) has
      been reported to increase the peritoneal clearances of urea and creatinine. This
      study investigated the effects of DSS on the fluid and solute transport
      characteristics of the peritoneum. DESIGN: A 4-h single-dwell experiment session
      of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an
      intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In
      eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was
      given to the other eight rats (control group). The transport of fluid, glucose,
      potassium, sodium, urea, phosphate and urate were analysed. RESULTS: There was a
      significant increase in the intraperitoneal volume in the DSS group. At 240 min,
      the drain volume in DSS group (33.0 +/- 2.9 ml) was significantly higher compared
      to the control group (28.8 +/- 2.1 ml, P < 0.01). This increase in the drain
      volume was mainly due to a decrease in peritoneal fluid absorption rate in the
      DSS group (0.040 +/- 0.013 ml/min) as compared to the control group (0.054 +/-
      0.010 ml/min, P < 0.05). There was no significant difference in the diffusive
      permeability and sieving coefficient for the small solutes between these two
      groups. However, the clearances for urea and sodium were higher in the DSS group,
      mainly due to the increase in the dialysate volume. CONCLUSION: Our results
      suggest that DSS significantly increases the net ultrafiltration of peritoneal
      dialysis. This effect, which was mainly due to a decrease in the fluid absorption
      rate, contributed to the increased clearances for urea and sodium. DSS did not
      alter the diffusive permeability and sieving coefficient for the small solutes.

PMID- 9198055
TI  - Reduced calcium dialysate in CAPD patients: efficacy and limitations.
AB  - BACKGROUND: The increasing use of 'reduced calcium' dialysate in CAPD patients
      treated with calcium-based phosphate binders has raised concerns that this could
      lead to negative calcium balance, worsening hyperparathyroidism, and osteopenia.
      METHODS: The present study was conducted to examine the possibilities (a) that
      1.25 mM calcium dialysate leads to negative calcium balance and worsening
      hyperparathyroidism, and (b) that conversely 1.25 mM calcium dialysate is still
      too high for some patients. We studied 22 patients who, after a 2-month run in
      using 1.75 mM calcium dialysate and aluminium hydroxide binders, entered a 3
      month phase of 1.25 mM calcium dialysate with continuation of aluminium hydroxide
      as the sole phosphate binder. The patients then entered a final 9-month phase in
      which dialysate calcium remained at 1.25 mM and calcium carbonate was substituted
      for aluminium hydroxide and progressively titrated to achieve optimum phosphate
      control. RESULTS: During the initial 3-month period, parathyroid hormone
      increased from 259, range 11-1149 to 405, range 16-1318 pg/ml (P = 0.0001) and
      ionized calcium decreased from 1.17 +/- 0.06 to 1.11 +/- 0.08 mM (P = 0.0004).
      The subsequent 9-month phase was associated with return of parathyroid hormone to
      baseline levels. Further dialysate calcium reduction to 0.6 mM was implemented in
      the four patients who became hypercalcaemic. CONCLUSION: This study has clearly
      shown that reduction of dialysate calcium to 1.25 mM can be harmful to CAPD
      patients if oral calcium availability is inadequate. It has also shown that
      dialysate calcium at 1.25 mM is a compromise, with increased risk of
      hyperparathyroidism if calcium intake is too low and, conversely, risk of
      hypercalcaemia and unacceptable increases of the Ca x Pi product in a minority of
      patients. At these extremes there is a need for a high-calcium dialysate (1.75
      mM) and a very low-calcium dialysate (0.6 mM or less), to optimize management.

PMID- 9198056
TI  - Disturbed latex immunoassays for C-reactive protein and ferritin in a renal
      transplant patient due to polyclonal IgM hypergammaglobulinaemia.
AB  - BACKGROUND: C-reactive protein (CRP) and ferritin serum levels represent routine
      laboratory parameters in the monitoring of renal failure patients. Analysis of
      CRP, ferritin and other serum proteins can be performed using latex-enhanced or
      non-latex-enhanced immunoassays. We report on a renal transplant patient with
      polyclonal IgM hypergammaglobulinaemia having markedly elevated serum CRP and
      ferritin levels (as detected by latex-enhanced immunoassays) in the absence of
      clinical signs of an infectious or malignant disorder. METHODS: CRP and ferritin
      serum levels were determined with various immunoassays with and without latex
      enhancement. To characterize the causative agent for the elevated CRP and
      ferritin values, the patient's and a control serum were fractionated by gel
      filtration on a Sephacryl S-300 column. Serum fractions were subjected to further
      analysis for reactivity in CRP and ferritin assays. In addition, patient's serum
      samples were investigated for reactivity with various other latex-based
      immunoassays (rheumatoid factor, antistreptolysin O, antistreptococcal DNase B).
      RESULTS: Using latex-enhanced CRP and ferritin immunoassays, markedly elevated
      serum levels were obtained (CRP 726 mg/l determined by turbidimetry, 398 mg/l
      determined by nephelometry; ferritin, 20,000 micrograms/l determined by
      turbidimetry). In contrast, assays without latex enhancement revealed levels
      within the normal range for both serum proteins (CRP < 5 mg/l, ferritin 52
      micrograms/l). The analysis of the patient's serum by gel filtration revealed an
      interference of the patient's IgM with latex particles used in the CRP and
      ferritin assays. CONCLUSION: Our study demonstrates that even polyclonal IgM
      hypergammaglobulinaemia can disturb a large array of latex-enhanced immunoassays
      used for routine diagnostic procedures. This is of particular interest for the
      management of allograft recipients in whom monoclonal and polyclonal
      gammaglobulinaemia are frequently observed. We therefore recommend reanalysis of
      the respective plasma proteins by latex-free assays in patients with
      hypergammaglobinaemia showing no clinical signs of an acute infectious disease or
      malignant disorder.

PMID- 9198057
TI  - Ultrasound-guided cannulation versus the landmark-guided technique for acute
      haemodialysis access.
AB  - BACKGROUND: The correct placement of large-bore venous catheters plays an
      important role in the management of haemodialysis patients. Whilst the procedure
      for landmark-based placement of these catheters is well known, the technique is
      not without significant morbidity and mortality. Complications include arterial
      puncture, haematoma, and pneumothorax. The procedure may be further complicated
      in these patients by venous thrombosis and abnormal vein position from multiple
      previous attempts at venous access. METHODS: Data on the use of ultrasound
      guidance versus anatomical landmarks for the placement of internal jugular vein
      (n = 69) and femoral vein (n = 30) dialysis access was retrospectively analysed
      over a 13-month period. Data collected included age, sex, duration on dialysis,
      number of vein cannulation sets required, number of attempts for successful
      cannulation, salvage of failed cannulation using landmark-based technique by
      ultrasound guidance, and the complication rate. RESULTS: Internal jugular vein
      cannulation using ultrasound was ultimately successful in 96.7% compared to 82%
      in the landmark group. The vein was entered on the first attempt in 83.3% of
      patients with ultrasound compared to 35.9% of the landmark group (P < 0.0001).
      Seven patients in whom the landmark technique was unsuccessful had access placed
      under ultrasound guidance. There were fewer carotid artery punctures in the
      ultrasound group (7.7 versus 0%, P = n.s.). In the femoral vein group, the vein
      was entered on the first attempt in 85.7% of patients with ultrasound compared to
      56.25% of the landmark group (P = n.s.). CONCLUSIONS: The use of ultrasound
      guidance is associated with fewer complications and is more likely to lead to
      cannulation of the vein at the first attempt in haemodialysis patients.

PMID- 9198058
TI  - Epitope-defined monoclonal antibodies against type-IV collagen for diagnosis of
      Alport's syndrome.
AB  - BACKGROUND: Alport's syndrome can be diagnosed by staining the alpha 5 chain of
      type IV collagen in kidney biopsy specimens with a monoclonal antibody. Because
      antibodies already established against the alpha 5 chain require denaturation
      treatment of cryostat sections to expose their epitopes. To save time and effort
      for staining, a new epitope-defined monoclonal antibody whose epitope is
      initially exposed on the surface of the molecule was established. METHODS: Two
      monoclonal antibodies against the triple-helical domains of the type IV collagen
      alpha 2 and alpha 5 chains were established with synthetic peptides as immunogens
      by the rat lymph node method. Their epitope were EAIQP at the positions of 675
      679 of the alpha 2 chain, and IDVEF at the positions of 251-255 of the alpha 5
      chain, respectively. They were purified with synthetic peptide-coupled affinity
      columns, and then conjugated with Texas red and FITC, respectively. RESULTS: The
      mixture of fluorochrome-conjugated antibodies was able to detect the distribution
      of the alpha 2 and alpha 5 chains in the normal and Alport kidney and skin by
      direct immunofluorescence staining with and without denaturation treatment of the
      sections. CONCLUSIONS: The direct double immunofluorescence staining of kidney
      and skin cryostat sections with the fluorochrome-conjugated antibodies is useful,
      reliable, and convenient for diagnosis of Alport's syndrome.

PMID- 9198059
TI  - Late occurrence of cysts in autosomal dominant medullary cystic kidney disease.
AB  - Medullary cystic kidney disease (MCD) is characterized by multiple renal cysts at
      the corticomedullary boundary area, by autosomal dominant inheritance, and by
      onset of chronic renal failure in the third decade of life. We report on a family
      with three affected individuals of both sexes in two generations presenting with
      end-stage renal failure at age 22-31 years. Primarily diagnoses considered
      included unclassified hereditary nephropathy and autosomal dominant polycystic
      kidney disease. Careful evaluation of all findings, initiated after investigation
      of renal morphology with CT, revealed features characteristic for MCD and led to
      the final diagnosis of MCD. We conclude that MCD is an important differential
      diagnosis for polycystic kidney disease in young adults with end-stage renal
      failure. Establishing the correct diagnosis has considerable impact for genetic
      counselling.

PMID- 9198060
TI  - Oral-facial-digital syndrome type I: an unusual cause of hereditary cystic kidney
      disease.

PMID- 9198061
TI  - Acquired Fanconi syndrome associated with IgG kappa multiple myeloma:
      observations on the mechanisms of impaired renal acid excretion.

PMID- 9198062
TI  - Severe hyperkalaemia after cotrimoxazole administration in a patient with
      hyporeninaemic hypoaldosteronism.

PMID- 9198063
TI  - Renal disease in Waldenstrom's macroglobulinaemia.

PMID- 9198064
TI  - Acute renal failure of unknown origin. Don't forget renal tuberculosis.

PMID- 9198065
TI  - Decrease in the haemoglobin level in haemodialysis patients undergoing
      antiandrogen therapy.

PMID- 9198066
TI  - Successful surgical revascularization of a kidney transplant after PTA-induced
      arterial dissection of the allograft renal artery.

PMID- 9198067
TI  - Thrombotic occlusion of ureteric stent: an unusual cause of anuria after kidney
      transplantation.

PMID- 9198068
TI  - Renal transplantation in a child with iliac vein thrombosis and absence of
      superior and inferior venae cavae.

PMID- 9198069
TI  - A proliferative vascular tumour of the skin in a kidney-transplant recipient
      (recurrent pyogenic granuloma with satellitosis).

PMID- 9198070
TI  - The diabetic foot: a frequently ignored and mismanaged problem.

PMID- 9198071
TI  - Hypocomplementaemic urticarial vasculitis.

PMID- 9198072
TI  - Vomiting, headache and seizures in a child with idiopathic nephrotic syndrome.

PMID- 9198073
TI  - Renal changes in the diabetic kidney.

PMID- 9198074
TI  - Current approach to exit-site infections in patients on peritoneal dialysis.

PMID- 9198075
TI  - Renal impairment induced by isotretinoin.

PMID- 9198076
TI  - Intracardiac thrombi in nephrotic syndrome.

PMID- 9198077
TI  - L-carnitine normalizes the reduced carnitine palmitoyl transferase activity in
      red cells from haemodialysis patients.

PMID- 9198078
TI  - High risk of severe endocarditis in patients on chronic dialysis.

PMID- 9198079
TI  - The set point of calcium-regulated PTH secretion as assessed in vivo: a
      physiological or artificial concept?

PMID- 9198080
TI  - Gastric emptying patterns of a liquid meal in newborn infants measured by
      epigastric impedance.
AB  - Epigastric impedance was used to measure the gastric emptying patterns of a
      liquid non-caloric meal (5 mL water kg-1) in 30 healthy newborn infants. Twenty
      six mature infants were examined in the first eight days of life, and four
      preterm infants were examined within 6 weeks after birth. The recordings
      consisted of two components: the emptying signal (the DC component), and a phasic
      3 cycles per minutes (CPM) signal (the AC component). In some of the infants the
      phasic 3 CPM signal was also seen during the fasting state. For mature infants
      the median half emptying time (T50) was 6.9 min. For a second meal given within
      one hour after the first meal the half emptying time was 5.5 min (P < 0.01). In
      preterm infants the emptying times were not significantly different from mature
      infants. Day-to-day variation was low with a coefficient of variation of 17% in
      nine infants. A periodic change of the impedance signal, the phasic 3 CPM signal,
      was observed after a meal in 24 of the infants. The median frequency was 3.0 CPM
      in 20 mature and 2.9 CPM in four preterm infants. In nine infants a phasic 3 CPM
      signal was also observed during the fasting state, with a median frequency of 2.9
      CPM. Measurement of gastric emptying pattern with epigastric impedance is a
      simple investigation for the evaluation of gastric emptying time and phasic
      activity in mature and preterm infants. However, the method is sensitive to
      spontaneous movements of the children, resulting in non-valid measurements in
      around one fourth of the infants.

PMID- 9198081
TI  - Colonic transit time in patients with myelomeningocele.
AB  - To evaluate colonic motility in patients with myelomeningocele, the transit time
      of radiopaque markers was studied in 22 patients with myelomeningocele and 22 age
      and sex matched controls. Mean colonic transit time was significantly longer in
      patients than in controls (103.2 +/- 49 h versus 23.3 +/- 13 h; P < 10(-7).
      Thirteen of 22 patients with myelomeningocele were severely constipated. Six
      patients had constipation secondary to delayed colonic transit, particularly in
      the left colon, and seven had increased rectosigmoid transit. The clinical
      questionnaire and particularly the frequency of bowel movements did not predict
      colonic transit. Among 13 patients with increased colonic transit, eight had more
      than five bowel movements per week and, thus, six of them did not use laxatives
      or enemas, despite the presence of faecal incontinence. There was no relationship
      between colonic transit time and the level of the spinal lesion or patient
      mobility in patients with myelomeningocele. Rectoanal dyssynergia was found in 14
      of the 22 patients, but equally often in patients with delayed rectosigmoid
      transit (4/7) as in the other patients (10/15) (P = ns). Uninhibited detrusor
      contractions were observed more often in patients with increased colonic transit
      time than in others (8/12 versus 1/8, P = 0.05). In the absence of a correlation
      between colonic transit time, clinical symptoms, anorectal motility, level of
      spinal lesion, patient mobility, evaluation of colonic transit of radiopaque
      markers should be assessed routinely in all patients with myelomeningocele to
      plan the most appropriate treatment, mainly in case of unhibited detrusor
      contractions.

PMID- 9198082
TI  - The effect of gravity on oesophageal peristalsis in humans.
AB  - Many mammalian species including non-human primates consume water in a body
      position not aided by gravity and it has been conjectured that oesophageal
      peristalsis overcomes gravity in humans. The purpose of this study was to
      determine the effects of gravity on oesophageal peristalsis in humans in response
      to water swallows. Six females (30-43 years old) and six males (27-46 years old)
      without oesophageal symptoms underwent oesophageal motility testing with
      intraluminal microtransducers placed 5, 7.5, 10 and 15 cm above the lower
      oesophageal sphincter. Subjects received ten 5 mL water swallows every 30 sec in
      the supine, standing, and head down (30 degrees) prone positions which were
      counterbalanced. Oesophageal contractile pressure (115, 98, 126 mmHg), duration
      (3.5, 3.0, 3.7 sec), onset velocity (4.7, 4.9, 4.7 cm sec-1), peak velocity (5.1,
      4.8, 4.1 cm sec-1), average upstroke (dP/dT) (78, 75, 84 mmHg sec-1), or maximum
      upstroke (132, 120, 141 mmHg sec-1) were not significantly different among the
      head down prone, upright and supine positions, respectively. The frequency of
      abnormal contractile activity was statistically different among the positions.
      More abnormal contractions (i.e. simultaneous, retrograde, non-transmitted)
      occurred in the upright position (26%) when compared to either the supine (12%, P
      = 0.005) or head down prone (13%, P = 0.013) positions. The oesophagus tends to
      function normally to water swallows when unassisted by gravity. Oesophageal
      peristaltic dysfunction to water swallows may be more pronounced when assisted by
      the force of gravity.

PMID- 9198083
TI  - Ambulatory long-term jejunal manometry in diabetic patients with cardiac
      autonomic neuropathy.
AB  - Concerning alteration of small bowel motility in diabetic patients with autonomic
      neuropathy controversial data were obtained with stationary manometry and over a
      limited period of time. The aim of our study was to examine ambulatory 24 h
      jejunal motility in 15 diabetic patients with cardiac autonomic neuropathy
      compared with data obtained in 50 healthy controls. Twenty-four hour motility was
      recorded in the proximal jejunum with a portable datalogger and tube-mounted
      miniature pressure sensors. Diurnal and nocturnal fasting motility and the motor
      response to a standardized evening meal of 600 kcal were evaluated by visual and
      computer-aided analysis. The following abnormalities were found during fasting
      motility (n = number of patients): absence of phase III over 24 h (n = 2),
      retrograde migration or simultaneous occurrence of phase III (n = 5). During
      postprandial motility irregular bursts with tonic baseline elevation (n = 3) and
      contraction frequencies below the range of controls (n = 8) occurred. Furthermore
      patients exhibited an inversion of the normal relationship between phase I and
      phase II during nocturnal MMC-cycles, and discrete clustered contractions were
      diminished (P < 0.01) in the fasting and digestive state. All patients showed at
      least one abnormal manometric finding. We conclude that small bowel motility in
      diabetic autonomic neuropathy is characterized by disturbances in the generation
      and aboral migration of phase III, an altered circadian variability of the MMC
      cycle and by postprandial hypomotility.

PMID- 9198084
TI  - Responses of the rat lower oesophageal sphincter (LOS) to vagal efferent
      activation.
AB  - Nitric oxide (NO) is a major candidate in vagal-induced LOS relaxation. Vagal
      adrenergic fibres also innervate the gastrointestinal tract including the LOS.
      This study investigates the role of these two and other mechanisms in LOS
      responses to vagal activation in the rat, and provides functional and anatomical
      evidence for a smooth muscle LOS in this species. LOS, gastric and oesophageal
      pressures were measured in urethane anaesthetized rats during vagal stimulation.
      The LOS pressure (LOSP) response to Vagal stimulation (5 mA, 10 Hz, 0.5 msec
      pulses, 5 sec) comprised three consecutive stages: (1) brief reduction of LOSP,
      (2) transient increase of LOSP and (3) prolonged reduction of LOSP. The
      influences of additive treatment with several antagonist drugs on the LOS
      response to vagal stimulation were investigated. L-NAME (100 mg kg-1) reduced
      stage 1 and increased stage 2. Subsequent treatment with either phentolamine (1
      mg kg-1) or prazosin (200 micrograms kg-1) abolished stage 1. After phentolamine,
      atropine treatment (400 micrograms kg-1) abolished stage 2. Stage 3 was evident
      throughout experiments. In five additional studies, treatment with hexamethonium
      (30 mg kg-1) abolished stages 2 and 3 leaving stage 1, which was later abolished
      by phentolamine or atropine. In the LOS response to vagal stimulation, the
      following major mechanisms are therefore evident: nicotinic transmission in both
      excitation and inhibition, alpha-adrenergic and NO-mediated inhibition,
      muscarinic excitation, and non-adrenergic, non-NO inhibition (not characterized
      further). Characteristics of these different neurotransmitter influences may be
      important in LOS relaxation associated with swallowing and gastro-oesophageal
      reflux.

PMID- 9198085
TI  - Colonic migrating motor complexes (CMMCs) in the isolated mouse colon.
AB  - Spontaneous contractions were recorded from the circular muscle layer at three
      sites along the isolated mouse colon. The interval between contractions was
      approximately 4.5 min. The mean duration of the contractions ranged from 26 sec
      in the distal colon to 45 sec in the proximal colon. Contractions migrating more
      than half the length of the colon were termed colonic migrating motor complexes
      (CMMCs). Over 90% of tissues demonstrated migration predominantly in an aboral
      direction. Hyoscine (10(-6) M) decreased the amplitude of the CMMCs by at least
      40% but had no significant effect on the interval or duration of the CMMCs.
      Nifedipine (10(-6) M) significantly decreased the amplitude of the CMMCs by 95%
      but did not alter the duration or the interval between the CMMCs. Hexamethonium
      (5 x 10(-4) M) and tetrodotoxin (TTX; 2 x 10(-6) M) abolished all CMMC activity.
      TTX increased the resting tone of the preparations. Nitro-L-arginine (10(-4) M)
      increased the resting tone of the preparations and significantly decreased the
      interval between the CMMCs by approximately 80% but had no significant effect on
      the duration of the CMMCs. The results suggest CMMCs migrate predominantly in an
      aboral direction and are neurogenic in origin. Nitric oxide may be involved in
      maintaining inhibition of the muscle between CMMCs.

PMID- 9198086
TI  - PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the
      DVC.
AB  - The pancreatic polypeptide family of hormones and neurotransmitters including
      pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) are
      emerging as potent central regulators of gastric function. There is, however,
      considerable debate concerning the mechanisms and even the direction of effects
      mediated by these peptides. Good evidence exists showing that PYY is the
      'enterogastrone' released by the ileum after feeding which acts on vagal reflex
      control circuits to reduce gastric motility (i.e. the 'ileal brake'). However,
      equally convincing evidence is available to suggest that PYY and its close
      structural relative NPY may act in the same region of the brain to increase
      gastric motility through vagal mechanisms. We hypothesize that the confounding
      observations are due to agonist effects on two different receptor types-Y1 and
      Y2, which are both present in the dorsal vagal complex (DVC) but may be accessed
      differentially by peripheral humoral (PYY) vs central (NPY) pathways. In our
      initial approach to this problem, we studied the effects of NPY, PYY, Y1 and Y2
      agonists microinjected into the DVC on gastric motility in the stimulated (by
      central thyrotropin-releasing hormone (TRH) and basal conditions. Our results
      show that Y2 agonist applied to the DVC during conditions of TRH-stimulated
      gastric motility mimicked the suppressive effects of PYY applied under the same
      conditions. Under basal conditions, Y2 agonist has no effect on motility. The DVC
      effect of the Y1 agonist is the opposite; Y1 agonist has no further effect to
      stimulate gastric motility in the TRH stimulated condition while Y1 agonist
      strongly stimulates motility from the basal condition. The effects of NPY depend
      upon the condition of study. Under TRH stimulation (maximal motility), NPY in the
      DVC reduces (but does not completely suppress) gastric motility while in the
      basal state, NPY is a strong activator of motility. These results are discussed
      in terms of the possible differential localization of Y1 vs Y2 receptors within
      the DVC and in terms of recent findings suggesting that PYY is rapidly converted
      to a Y2 agonist by a ubiquitous dipeptidyl aminopeptidase (DAP-IV).

PMID- 9198087
TI  - Superior laryngeal nerve stimulation in the cat: effect on oropharyngeal
      swallowing, oesophageal motility and lower oesophageal sphincter activity.
AB  - Superior laryngeal nerve (SLN) stimulation can activate the brainstem swallowing
      mechanism to produce a complete swallowing sequence consisting of oropharyngeal,
      oesophageal and lower oesophageal sphincter (LOS) components. However, little is
      known of the effect of SLN stimulation (peripheral-sensory input from the
      pharynx) on the characteristics of oesophageal motor activity, especially in the
      smooth muscle portion. The present study examined the effect of varying stimulus
      train length and frequency on each of the three components of the reflex. Acute
      studies were performed in urethane anaesthetized cats. Oesophageal motility was
      monitored using conventional manometric techniques, and oropharyngeal swallowing
      by the mylohyoid electromyogram. SLN stimulus train length (1-10 sec) and
      frequency (5-30 Hz) were varied independently. Increased train length or
      frequency resulted in (1) an increase in oropharyngeal swallowing and incidence
      of the complete swallowing response, (2) an increase in latency to onset of the
      oesophageal peristaltic wave, (3) reduction of the amplitude of the evoked
      peristaltic contraction in the smooth muscle portion, without altering its
      velocity, (4) increased LOS relaxation, and increased LOS after-contraction. The
      LOS contraction was abolished by atropine (100 micrograms kg-1). Therefore,
      increased SLN stimulation not only results in excitation of the central
      swallowing program and the oropharyngeal stage of swallowing, but has major
      effects on the oesophageal and LOS stages of swallowing. Afferent SLN stimuli can
      impact on the control mechanisms for each stage, to inhibit or excite the stages
      in different ways.

PMID- 9198088
TI  - The cerebral response to electrical stimuli in the oesophagus is altered by
      increasing stimulus frequencies.
AB  - Recording of cerebral evoked responses (EP) allows the assessment of visceral
      afferent pathways and gut-brain communication, but the optimal stimulation
      parameters remain to be established. The present study determined the optimal
      stimulation frequency of electrical stimulation of the oesophagus to elicit EP
      responses. In 13 healthy male volunteers (24.1 +/- 5.9 years), a 5 mm stainless
      steel electrode was placed in the distal oesophagus for electrical stimulation
      (ES). EP were recorded from 21 scalp electrodes placed according to the 10/20
      International system. ES (15 mA, 200 microseconds) were delivered in repeated
      series of 24 stimuli. Stimulus frequency was randomly altered in different series
      using a pseudologarithmic range (0.1, 0.2, 0.3, 0.5, and 1 Hz). Two series of
      stimuli were applied using each stimulation frequency. Two-dimensional
      topographic brain maps were created using interpolation techniques at each
      stimulation frequency. With increasing stimulus frequency, a significant and
      progressive decrease of EP amplitudes was observed between frequencies of 0.1 Hz
      and 1.0 Hz (P1/N2: 7.6 +/- 1.2 vs 1.4 +/- 0.3* microV, N2/P2: 17.2 +/- 1.7 vs 4.6
      +/- 0.4* microV, P2/N3: 6.9 +/- 0.7 vs 4.2 +/- 0.5* microV; * = P < 0.05). In
      addition, there was a significant shortening of the mean peak latency of the
      intercalated P2 peak (P < 0.0005), with a similar trend for the P3 peak (P <
      0.06), with increasing stimulus frequency from 0.1-1.0 Hz. Topographic brain maps
      localized the maximal early peaks (N1,P1.N2) in the paracentral cortical region
      (C3, Cz, C4), whereas the later peaks (P2 to P3) were symmetrically spread over
      the centroparietal and temporal regions (Cz, Pz, T5, T4). There was no difference
      in the cortical location of maximal EP amplitudes with increasing stimulus
      frequency. In conclusion, there is a clear relationship between stimulus
      frequency and amplitude of EP, suggesting rapid attenuation of the cerebral
      autonomic neural responses with increased electrical stimulation frequency. The
      effect of increased frequency on peak latencies suggests an alteration of
      stimulus processing in the thalamocortical region due to an altered perception of
      stimuli. Early EP peaks originate from basal structures of primarily the dominant
      hemisphere, while later peaks are localized in centroparietal cortical regions.

PMID- 9198089
TI  - [Treatment of neurological disorders with botulinum toxin: recent progress].

PMID- 9198090
TI  - [Cell transplantation for neuronal and muscular disorders].

PMID- 9198091
TI  - [Malignant syndrome in multiple system atrophy].
AB  - Five of fourteen patients with multiple system atrophy (MSA) experienced a total
      of eight episodes of malignant syndrome, three episodes in 1, two episodes in 1
      patient, and a single episode in each of the other patients. Four patients had
      extrapyramidal symptoms and required antiparkinson therapy, including
      dopaminergic agonists. Five episodes occurred in the summer season. Two were
      caused by decreased or irregular doses of antiparkinson drugs, one by
      administration of an antidepressant drug, three by complications, and two by
      elevation of body temperature of environmental origin. A patient without
      parkinsonism became febrile after administration of droxidopa, which may be a
      central pyrogenic substance that acts via the noradrenergic system.
      Administration of dopaminergic drugs and dantrolene sodium was followed by
      recovery in four episodes in three patients. One patient manifested dysautonomia
      after recovery from the malignant syndrome. Another patient with high serum
      creatine kinase levels and myoglobinuria developed renal failure requiring
      hemodialysis. Another patient died of DIC. Besides withdrawal of dopaminergic
      agents, which alter monoaminergic neuron activity, stress to the body and heating
      by a variety of factors tend to trigger the malignant syndrome in MSA.

PMID- 9198092
TI  - [Study on potentiation of nitrosourea-cytotoxicity by DNA repair enzyme
      inhibitors in human brain tumor cells].
AB  - Nitrosoureas are antitumor alkylating agents widely used in the chemotherapy of
      malignant brain tumors. However, the effectiveness of adjuvant nitrosourea
      chemotherapy has proved inadequate, failing to provide any significant
      prolongation of survival time. One of the reasons for the poor results is a drug
      resistance system in the form of the DNA repair enzyme O6-methylguanine-DNA
      methyltransferase (MGMT). O6-alkylguanine derivatives are well known to be
      inhibitors of MGMT, and inactivation of MGMT by these derivatives leads to
      increased tumor cell sensitivity to nitrosoureas. In this study, the authors
      tested the ability of O6-benzylguanine, O6-(4-, 3- and 2-fluorobenzyl) guanines,
      O6-(4-, 3- and 2-trifluoromethylbenzyl) guanines, O6-(4-, 3- and 2-pyridylmethyl)
      guanines and O6-(2- and 1-naphthylmethyl) guanines to reduce MGMT activity in SF
      188 cell-free extract by using [3H] methylated substrate DNA and analyzed their
      enhancing effect on the cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl
      3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) by using a calorimetric
      cytotoxicity assay. The MGMT activity in the SF-188 cell-free extract was 944 +/-
      43 fmol/mg protein (Mean +/- SD, n = 5). O6-(4- and 3-fluorobenzyl) guanines were
      found to be more effective in inactivating MGMT than O6-benzylguanine. O6-(4
      trifluoromethylbenzyl) guanine considerably reduced MGMT activity as did O6
      benzylguanine. O6-(3-trifluoromethylbenzyl) guanine, O6-(4- and 3-pyridylmethyl)
      guanines, and O6-(2-naphthylmethyl) guanine were intermediately effective, but O6
      (2-fluorobenzyl) guanine, O6-(2-trifluoromethylbenzyl) guanine and O6-(1
      naphthylmethyl) guanine were less effective. ACNU cytotoxicity in SF-188 cells
      was strongly enhanced by pretreatment with O6-(4- and 3-fluorobenzyl) guanines
      and O6-(4-trifluoromethylbenzyl) guanine and moderately enhanced by O6-(3-
      trifluoromethylbenzyl) guanine and O6-(4- and 3-pyridylmethyl) guanines, but not
      enhanced by O6-(2-fluorobenzyl) guanine, O6-(2-trifluoromethylbenzyl) guanine and
      O6-(1-naphthylmethyl) guanine. The test compounds were not cytotoxic at
      concentrations between 0.5 and 5.0 microM. The enhancing effects on ACNU
      cytotoxicity were consistent with the inhibition of MGMT activity after two-hour
      pretreatment with O6-arylmethylguanine derivatives. These results indicate that
      the 2-position of the O6-benzyl group plays an important role in the inactivation
      of the MGMT activity and the potentiation of ACNU cytotoxicity.

PMID- 9198093
TI  - [Motor function outcome and changes in motor impairment level of the upper limbs
      and fingers in patients with acute carotid-system cerebral infarction].
AB  - Early diagnosis of motor function status and changes in motor impairment level of
      the upper limbs and fingers in patients with acute cerebral infarction is
      important in establishing a treatment plan. This study investigated a method of
      predicting motor function outcome and changes in motor impairment based on the
      characteristics of symptoms on admission and severity according to the CT
      classification. The subjects were 309 patients with carotid-system cerebral
      infarction admitted on the day of onset of symptoms and who exhibited a low
      density area in the territory of the middle cerebral artery on CT images within 5
      day of the onset of symptoms. The motor function level was evaluated according to
      Brunnstrom's stage. The findings were as follows: 1) The motor function level of
      the upper limbs and fingers improved to stage 3 or more in patients without
      unilateral neglect. 2) Complete recovery of motor impairment of the upper limbs
      and fingers was observed in 163 patients (54.7%). Motor impairment of the upper
      limbs recovered within 3 weeks after the onset in 121 patients, and from 22 days
      to 3 months after the onset in the remaining 42 patients. Similarly, motor
      impairment of the fingers recovered within 3 weeks after the onset in 113
      patients, and between 22 days and 3 months after the onset in the remaining 50
      patients. 3) Stage 4 or higher motor impairment grade on admission was seen in
      107 (88.4%) of the patients with recovery of impaired motor function in the upper
      limbs within 3 weeks after the onset. Similarly, stage 4 or higher was seen in
      101 (89.4%) patients with recovery of impaired motor function of the fingers
      within 3 weeks after the onset. 4) Of the 44 patients with recovery of impaired
      motor function of the upper limbs between 22 days and 3 months after the onset,
      30 improved to stage 4 by 2 weeks after the onset and to stage 6 by one month.
      The remaining 12 patients improved to stage 5 by one month after the onset and to
      stage 6 by 3 months. Of the 50 patients with recovery of impaired motor function
      of the fingers between 22 days and 3 months after the onset, 44 improved to stage
      4 by 2 weeks after the onset and to stage 6 by one month. The remaining 6
      patients improved to stage 5 by one month after the onset and to stage 6 by 3
      months. 5) Progressive stroke was observed in 60 patients (20.1%). All patients
      with progressive stroke showed unilateral neglect on admission. 6) Completed
      stroke, excludise of progressive stroke, was seen in 75 patients (24.3%). In the
      patients with completed stroke, there was clearly no improvement in the motor
      impairment of the limbs and fingers over 3 months after onset. 7) It was
      difficult to predict motor function level at the time of discharge based on the
      evaluation of stage on admission and the location of the low density area on CT.
      8) Our CT classification was closely correlated with the motor function outcome
      of the upper limbs and fingers. Therefore, this classification and assessment of
      whether unilateral neglect is present on admission may be useful in predicting
      motor function outcome and changes in motor impairment of the upper limbs and
      fingers early after the onset of acute cerebral infarction.

PMID- 9198094
TI  - [Cerebral infarction due to bacterial emboli associated with methamphetamine
      abuse].
AB  - The number of stimulant-drug addicts has recently been on the rise again, and
      they are being increasingly encountered in the emergency room. There are also
      frequent reports of cerebrovascular disorders complicating drug toxicity. These
      cerebrovascular disorders have included subarachnoid hemorrhage, intracranial
      hematoma, and a few cases of cerebral infarction. Here, we report the case of a
      37-year-old male with drug toxicity, consciousness disorder, and hyperthermia. He
      was in a coma with a temperature of 43.1 degrees C and blood pressure of 58/35
      mmHg when brought to our hospital. His condition worse rapidly deteriorated, and
      he died the same day. Cerebral infarction caused by gram-positive bacillus
      embolism, not necrotizing angiitis, was found at autopsy. Because drug addicts,
      especially stimulant-drug addicts, tend to inject themselves drug under
      unsanitary conditions, the possibility of this type of complication is always
      present. This is the first such case ever reported, and is therefore regarded as
      a rare complication of stimulant-drug intoxication.

PMID- 9198095
TI  - [A patient with spontaneous intracranial hypotension--comparison between MRI
      findings and meningeal pathology].
AB  - We report a 44-year-old woman with spontaneous intracranial hypotension (SIH) who
      developed an acute, severe, nonthrobbing headache. The headache remained more
      severe in the occipital region and was markedly worse with upright posture.
      Cerebrospinal fluid (CSF) examination revealed an opening pressure of 55 mmH2O,
      and the CSF contained 38 cells/mm3 and 57 mg/dl of protein. The results of other
      laboratory examinations were unremarkable. T1-weighted MR images (MRI) of the
      head revealed an extensive diffuse pachymeningeal gadolinium enhancement and
      bilateral subdural fluid accumulation. On the 21st hospital day, a meningeal
      biopsy was performed through a right parietal craniotomy. On histologic
      examination, the dural border cell layer demonstrated nonspecific granulation
      tissue with mild inflammatory changes. The remaining layers of the dura mater and
      the arachnoid membrane showed no obvious pathological changes. We speculated that
      the inflammatory changes of the dural border cell layer correspond to the zone of
      pachymeningeal gadolinium enhancement of the MRI. The granulation tissue of the
      dural border cell layer and subdural fluid accumulation may represent secondary
      reactive phenomena, and were suspected to have been caused by downward
      displacement of the brain due to decreased intracranial pressure.

PMID- 9198096
TI  - [Brain stem glioma presenting with contralateral sensory impairment of ascending
      nature].
AB  - A case of brain stem glioma, presenting with impairment of contralateral pain
      temperature sense of ascending nature, is reported. A 38-year-old woman with
      documented neurofibromatosis type 1 (NF-1) was admitted to our hospital for
      treatment, complaining of diminished pain-temperature sense in the left lower
      extremity. On admission, the symptom was first evaluated to be due to cervical
      myelopathy although motor involvement was absent. An MRI, myelography and CT
      myelography of the cervical spine were done, demonstrating no abnormality.
      Shortly after the admission the sensory impairment progressed to the upper chest
      level and then to the upper extremity on the left. Because of her documented NF-1
      a brain CT was checked, revealing a small mass with ring enhancement in the
      dorsal midbrain on the right. On MRI, the tumor location was at the right
      dorsolateral tectal region of superficial situation. Under the diagnosis of
      midbrain glioma the tumor was partially removed by the occipital transtentorial
      approach. At operation, the tumor has grown intraaxially, having pinkish-gray
      color and central necrosis. Histologically the tumor was diagnosed as
      glioblastoma multiforme. Postoperatively she presented a definite improvement of
      the sensory impairment in the reverse order, that is from upper extremity and
      then to the lower extremity. Progression and post-treatment improvement of the
      impaired pain-temperature sense in this case suggested that the topography and
      lamination of the lateral spinothalamic tract might be present even in the dorsal
      midbrain, namely the posterior-superficial layer to be sacral segment and the
      anterior-deep layer to be cervical one.

PMID- 9198097
TI  - [Ruptured fusiform aneurysm of the basilar artery with minimal atherosclerosis-
      report of a case].
AB  - We reported a case of ruptured fusiform aneurysm of the basilar artery with
      minimal atherosclerosis. A 51-year-old man was admitted because of subarachnoid
      hemorrhage (SAH). He had no previous illness and family history. Computed
      tomographic scan revealed subarachnoid hemorrhage and a fusiform aneurysm in the
      basilar artery. Cerebral angiography confirmed the presence of the basilar
      fusiform aneurysm. After four days, the consciousness level worsened and a
      respiratory support was initiated. The patient died on the fifth hospital day.
      Autopsy was permitted only to the brain. The brain weighed 1,700 g. Massive
      subarachnoid hemorrhage was noted at the base of the brain and in the sylvian
      fissures. A large fusiform aneurysm (30 x 20 x 17 mm) was located in the proximal
      portion of the basilar artery. Atherosclerotic changes were minimal in the
      aneurysmal wall and the major extracerebral arteries. SAH was most severe around
      the aneurysm. The pons showed focal necrosis due to compression by the aneurysm.
      Microscopically, the aneurysmal wall revealed diffuse attenuation of the
      muscularis. The elastica also showed a focal defect. We suggest that in the
      present case of fusiform aneurysm, the pathogenesis is not atherosclerosis but a
      congenital defect of the muscularis and elastic lamina.

PMID- 9198098
TI  - [A case of basilar artery occlusion associated with one-and-a-half syndrome,
      paralytic pontine exotropia and WEBINO-syndrome].
AB  - We report a 79-year-old woman with basilar artery occlusion. She had a sudden
      onset of tetraplegia and disturbed consciousness, and within four days from the
      onset she showed a varied, fluctuating eye symptoms. On admission, she showed
      ocular bobbing, skew deviation with the right eye lower-positioned, upward gaze
      palsy, one-and-a-half syndrome, and paralytic pontine exotropia (PPE). On the
      third day after the onset, she showed wall-eyed bilateral internuclear
      ophthalmoplegia (WEBINO) syndrome, and on the fourth day, she showed one-and-a
      half syndrome again. Her right-gaze palsy improved repeatedly, and on the 19th
      day from the onset, only right MLF syndrome remained. Her eye symptoms fluctuated
      probably according to the distal migration of emboli, there by the responsible
      lesion and the mechanism of these eye symptoms are considered to be closely inter
      correlated. On the fourth day after onset, the magnetic resonance imaging
      revealed cerebral infarctions in bilateral middle pons, the left paramedian lower
      pons, and the right paramedian midbrain, and a hemorrhagic infarction in the
      right inferior cerebellar hemisphere. We believe that that the eye symptoms of
      this patient were caused by lesions in the paramedian midbrain or pons.

PMID- 9198099
TI  - [Magnetic resonance imaging of Kernohan's notch in chronic subdural hematoma].
AB  - Compression of the crus cerebri against the free edge of the tentorium
      contralateral to a supratentorial mass, the so-called Kernohan's notch, can be a
      cause of false localizing sign. Kernohan's notch has been thoroughly studied
      clinically and pathologically, but not radiographically. The authors describe a
      case of left chronic subdural hematoma, which resulted in left hemiparesis caused
      by Kernohan's notch. Injury to the contralateral cerebral peduncle was clearly
      shown by magnetic resonance imaging (MRI) performed in the postoperative period.
      A 43-year-old man was transferred to our hospital in deep coma with dilated
      pupils, unreactive to light. Computed tomography (CT) scans obtained on admission
      revealed a left chronic subdural hematoma and a midline shift to the right. After
      drainage and irrigation of the left chronic subdural hematoma through a single
      burr hole, his clinical condition improved gradually. But 1 month after the
      operation, mild left hemiparesis still persisted. MRI T2-weighted images
      demonstrated an abnormally increased signal area in the right cerebral peduncle.
      T1-weighted coronal images showed the anatomical relationship between the
      hypointense lesion in the right cerebral peduncle and tentorial edge. Three
      dimensional-MRI (3D-MRI) clearly demonstrated the surface image of Kernohan's
      notch. We emphasize the utility of 3D-MRI for detecting evidence of brain stem
      injury, such as Kerno han's notch.

PMID- 9198100
TI  - [Abducens palsy].

PMID- 9198101
TI  - [A 64-year-old woman with severe headache and progressive disturbance of
      consciousness].
AB  - We report a 64-year-old woman who developed nausea, headache, and consciousness
      disturbance. She was well until four years before the onset of her neurologic
      illness when (April of 1990 at her 59 years of the age) she was found to have an
      early cancer in her anterior wall of the lower stomach. Subtotal gastrectomy was
      performed and the operative result was reported as curative. Four years after the
      surgery (December of 1994 at her 64 years of the age), she noted suboccipital
      headache and nausea which had become progressively worse and she was admitted to
      our service on May 24, 1995. On admission, she appeared chronically ill but
      general physical examination was unremarkable with normal vital signs.
      Neurologically she was alert and not demented, and the higher cerebral functions
      were intact. Cranial nerves were also unremarkable. She was able to walk in
      tandem and on heels. No motor weakness or ataxia was noted. Deep tendon reflexes
      were moderately increased, however, no Babinski sign was noted. Although she had
      headache, no meningeal signs were seen. Slight superficial and vibratory sensory
      loss was noted in both feet. Routine blood work was again unremarkable except for
      slight increase in CEA to 8.3 ng/dl (N < 5 ng/dl). The opening pressure of lumbar
      CSF was 180 mm H2O and the CSF contained 39 cells/microliter, 79 mg of protein,
      and 10 mg/dl of glucose. Approximately half of the cells were atypical malignant
      cells. Plain CT was unremarkable, however, tentorial border showed enhancement
      after contrast infusion. FGS showed no malignant tumors in the stomach. She was
      treated with intravenous glycerol and whole brain radiation, however, she
      continued to complain of severe headache, and her sensorium started to be
      disturbed one month after the admission. Follow-up cranial CT scan revealed
      enlargement of the lateral and the third ventricles. Her consciousness
      progressively deteriorated and she became comatose three months after the
      admission. Repeated cranial CT scan showed enlargement of the ventricles, but no
      mass lesions were seen within the brain. She developed respiratory arrest on
      September 25 of the same year. She was discussed in a neurological CPC and the
      chief discussant arrived at the conclusion that the patient had a gastric cancer
      with meningeal seeding developing meningeal carcinomatosis. The cause of deep
      coma was ascribed to damage of cerebral cortical areas secondary to metastatic
      carcinoma cells and fibrinous materials in the surface of the brain. Postmortem
      examination revealed thickening and clouding of leptomeninges of the cerebral
      convexity. On histologic observation, patchy areas of fibrous thickening were
      seen in the cerebral leptomeninges; in such areas, adenocarcinomatous cells were
      seen scattered. The basal meninges were free of carcinoma cells, however,
      leptomeninges of the cerebellum and brain stem tegmentum contained scattered
      carcinoma cells. The lateral and the third ventricles were enlarged, however,
      insides of the brain were free of pathologies; the ependymal layer were intact.
      In the stomach no carcinoma cells were remaining. Pneumonic changes were seen in
      the right upper and the left lower lobes which appeared to be the direct cause of
      her death. No evidence of tentorial herniation was noted. The cause of her deep
      coma was not clearly determined, however, combination of hydrocephalus and
      cortical malfunction due to leptomeningeal carcinoma cell infiltration and
      fibrinous material accumulation appeared to have played a role.

PMID- 9198102
TI  - Carcinoma in basal cell adenoma of the parotid gland.
AB  - Malignant transformation of basal cell adenoma (BCA) of the parotid gland is
      rarely reported, and when occurred, may principally become manifest as a
      malignant basaloid tumor, i.e. basal cell adenocarcinoma or adenoid cystic
      carcinoma. We describe herein three cases of non-basaloid carcinoma arising in
      BCA. The incidence of this malignant tumor was 0.2% of all parotid gland tumors
      and 4.3% of BCAs in our series. One case was salivary duct carcinoma showing
      histologic evidence of transition between malignant and benign elements. The
      remaining two cases were well-encapsulated parotid gland tumors, which were
      composed of BCA and scattered foci of malignant transformation. Malignant
      components were adenocarcinoma, not otherwise specified (NOS), and sometimes
      intermixed with neoplastic myoepithelial cells included BCA cells. These two
      cases were regarded to be intracapsular carcinoma in BCA. BCA components showed
      solid, tubular and trabecular arrangements. The patients' prognosis was quite
      variable among these three cases; the first case died of disease after 27 months,
      whereas the latter two cases are alive and well for 4 and 10 years after surgery.
      Ki-67 labeling index indicated that cell proliferative activity was at least five
      times higher in carcinomas than BCAs. Non-basaloid carcinomas such as salivary
      duct carcinoma or adenocarcinoma, NOS, do develop in BCAs as in the case of a
      pleomorphic adenoma with malignant transformation, though the incidence may be
      extremely rare.

PMID- 9198103
TI  - Immunohistochemical study of secretogranin II in 62 neuroendocrine tumours of the
      digestive tract and of the pancreas in comparison with other granins.
AB  - An immunohistochemical study on 62 cases of gastrointestinal and pancreatic
      neuroendocrine tumours was performed in order to test the interest and
      specificity of a new anti-human secretogranin II antibody and compared to the
      other granin markers (chromogranin A and chromogranin B). Specific
      immunoglobulins were purified by affinity chromatography from an antiserum raised
      against a recombinant secretogranin II. Gastric tumours did not express
      secretogranin II, and ileal and appendiceal tumours only rarely expressed it
      (1/10 and 1/7 respectively), unlike the other classic neuroendocrine members of
      the granin family. In duodenal and pancreatic tumours, secretogranin II was
      detected when the other granins were also expressed. On the other hand, all
      rectal tumours expressed secretogranin II (7/7), frequently in the absence of
      chromogranin A. Though the granins expressed in tumoral tissue and in adjoining
      non tumoral tissue are mostly related, strong secretogranin II positivity
      occurred in 4 tumours while mucosa was secretogranin II negative. These
      observations highlight the interest for associating another antigranin such as
      secretogranin II to the classical markers of neuroendocrine tumours.

PMID- 9198104
TI  - Morphologic effects of neoadjuvant chemotherapy in locally advanced breast
      cancer.
AB  - The use of chemotherapy as primary treatment in early and locally advanced breast
      cancer is rising. As a result, many resected tumors were exposed to cytotoxic
      drugs in vivo. To study resulting histopathologic changes, we examined 61
      patients with locally advanced stage III breast cancer who had been treated with
      a standardized neoadjuvant polychemotherapy regimen before undergoing surgical
      resection 3 months later. Matched pairs of pre- and posttherapy breast tissue
      were evaluated for morphologic changes in the residual malignant and benign
      breast tissue compartment. A potential correlation between changes and the
      original p53 immunophenotype was examined as well. In 11 cases (18%), complete
      pathologic remission with no residual tumor in the mastectomy specimen was
      achieved. This response was not correlated to the original p53 status. The
      remaining 50 cases showed residual tumor. The most prominent histologic change
      was an increase in nuclear atypia of tumor cells (51% of the cases). This effect
      was independent of the presence or absence of nuclear p53 accumulation in the pre
      treatment specimens. Nuclear atypia was frequently accompanied by tumor cell
      enlargement (in 49% of the cases). Most commonly, a tumor with relatively small
      cells presented with large epithelioid apocrine features after treatment. In 6
      cases (13%), the mitotic rate decreased significantly, while in 12 cases (26%)
      the mitotic rate increased after chemotherapy. Elston histogrades remained
      unchanged in 70% of the cases but increased in 17% and decreased in 13%, mainly
      due to changes in mitotic rates. Extensive tumor cell vacuolization, a common
      change seen after radiotherapy, was a minor finding but was seen focally. Within
      the non-malignant compartment, lobular atrophy with hyalinization and minimal
      epithelial atypia of lobules and ducts were common. We conclude that changes in
      residual tumor and normal breast are common following systemic cytotoxic therapy.
      As neoadjuvant chemotherapy becomes mainstream management for locally advanced
      breast cancer, pathologists are required to recognize treatment induced changes.
      For correct histopathologic assessment, therapy induced morphologic alterations
      need to be distinguished from tumor-intrinsic morphologic features.

PMID- 9198105
TI  - "Diabetic mastopathy" in the male breast--a special type of gynecomastia. A
      comparative study of lymphocytic mastitis and gynecomastia.
AB  - Focal B-lymphocytic mastitis and focal fibrosis of the breast in young women have
      rarely been reported as a complication of longstanding insulin-dependent diabetes
      mellitus type I. We present two cases of "diabetic mastopathy" in male diabetics
      suffering from gynecomastia. Furthermore, these two cases were examined in
      comparison to a selected group of 6 patients showing gynecomastia with a marked
      inflammatory reaction, as well as to 24 non-selected cases of common
      gynecomastia. The lesion is interpreted as a diabetes-induced autoimmune reaction
      of the breast and may be regarded as a lympho-epithelial lesion. Its
      histopathological characteristics are a marked chronic periductal and
      perivascular mastitis with a predominance of B-lymphocytes, a focal homogenous
      fibrosis and so called "epithelioid stromal fibroblasts" within the fibrotic
      matrix. Our findings support the existance of "diabetic mastopathy" in the male
      and point out to the potentially misleading pattern of this benign tumor-like
      lesion simulating gynecomastia.

PMID- 9198106
TI  - Ultrastructural differentiation of epidermolysis bullosa subtypes and porphyria
      cutanea tarda.
AB  - Identifying subtypes of epidermolysis bullosa clinically, particularly at the
      time of disease onset, can be extremely difficult. In this investigation samples
      of intact skin from cases of epidermolysis bullosa and porphyria cutanea tarda
      were examined ultrastructurally and compared with normal tissue. The histological
      composition of the blister roof and floor surfaces was also evaluated. Three of
      the ten epidermolysis bullosa subtypes examined revealed specific features.
      Distinctive, circumscribed, clumped tonofilament bodies were present in basal
      keratinocytes from epidermolysis bullosa herpetiformis Dowling-Meara. Blister
      formation in epidermolysis bullosa simplex generalisata gravis occurred
      immediately above the dermo-epidermal junction aspect of stratum basale cells and
      thick (30 nm diameter), cross-striated anchoring fibrils were absent in
      epidermolysis bullosa dystrophica generalisata gravis. Features relating to the
      lamina densa of the dermo-epidermal junction, dermal capillaries and blister
      composition were distinctive, but not confined to a particular epidermolysis
      bullosa subtype or porphyria cutanea tarda.

PMID- 9198107
TI  - Breast carcinoma with myeloid metaplasia--a case report.
AB  - A 49 year-old female had been suffering from primary myelofibrosis since February
      1987 without receiving any treatment. In 1994, a breast mass was detected. Breast
      tumor biopsy revealed tubular carcinoma with intraductal components and
      multinucleated giant cells in the loose and myxoid stroma. The giant cells were
      thought to be megakaryocytes because both Factor VIII and platelet glycoprotein
      GP IIIa were detected in their cytoplasm. While additional mastectomy specimens
      and the axillary lymph nodes also revealed prominent myeloid metaplasia, there
      was no proliferation of the cancer cells. Granulocytic series stained for
      chloroacetate esterase and very few erythrocytic series were observed. This is
      the first case in which breast carcinoma and myeloid metaplasia coexisted in the
      same breast tumor.

PMID- 9198108
TI  - Placental site trophoblastic tumor (PSTT) initially misdiagnosed as cervical
      carcinoma.
AB  - The placental site trophoblastic tumor (PSTT) is the rarest form of trophoblastic
      disease and shows a wide spectrum of symptoms. A 32-year-old women is presented
      with PSTT after abruptio in the 7th week of gestation which was initially
      misdiagnosed as cervical carcinoma on cervical punch biopsy. Therefore, a radical
      Wertheim-Held hysterectomy was done. The uterus showed a small tumor restricted
      to the cavum with no cervical infiltration, resembling in all histologic and
      immunohistochemical features a PSTT. The pelvic lymph nodes showed no metastases.
      There was no nephrotic syndrome. The patient showed no evidence of disease
      fourteen months after hysterectomy.

PMID- 9198109
TI  - Accumulation and distribution of free folic acid content in red beet (Beta
      vulgaris L.).
AB  - Among vegetable plants, red beet contains a relatively high level of the B
      vitamin folic acid. Although many leafy green vegetables contain high levels of
      folic acid, red beet is consumed primarily as a root vegetable. Folic acid levels
      have been quantified in various vegetable plants, but little information exists
      regarding the accumulation and distribution of this vitamin in plant tissues. The
      objective of this study was to characterize free folic acid content (FFAC) in
      shoot and root tissue during growth of two red beet inbreds. Experiments were
      conducted in a greenhouse during 1993, 1994 and 1995. Two inbreds, W384 and W357,
      were planted in randomized complete blocks and shoot and root tissues were
      separately harvested at 60, 80, and 100 days after planting (DAP). Significant
      differences between years, tissue portions, and among harvest dates were
      detected, however, similar patterns in FFAC accumulation and distribution were
      observed between inbreds and years. FFAC in shoot tissue was significantly
      greater than root tissue for both inbreds. Accumulation of FFAC was linear for
      both inbreds across harvest dates for root tissue but not for shoot tissue. FFAC
      accumulation in shoot tissue increased sharply from 60 to 80 DAP but decreased
      sharply from 80 to 100 DAP. These results demonstrate that FFAC accumulates
      differentially in root and shoot tissue in a red beet plant. Maximum folic acid
      levels in shoot tissue are achieved prior to those in root tissue.

PMID- 9198110
TI  - Effect of Tulasi (Ocimum sanctum) leaf powder supplementation on blood sugar
      levels, serum lipids and tissue lipids in diabetic rats.
AB  - Tulasi leaf powder was fed at the 1% level in normal and diabetic rats for a
      period of one month to explore the effect on fasting blood sugar, uronic acid,
      total amino acids, and the lipid profile in serum and tissue lipids. The results
      indicated a significant reduction in fasting blood sugar, uronic acid, total
      amino acids, total cholesterol, triglyceride, phospholipids and total lipids. In
      liver, total cholesterol, triglyceride and total lipids were significantly
      lowered. Total lipids were significantly reduced in kidney. In heart, a
      significant fall in total cholesterol and phospholipids was observed. All these
      observations indicate the hypoglycemic and hypolipidemic effect of Tulasi in
      diabetic rats.

PMID- 9198111
TI  - Evaluation of selected food characteristics of three advanced lines of Nigerian
      soybean (Glycine max (L.) Merr.).
AB  - The seeds of three promising advanced lines of soybeans (TGx 923-2EN, TGx 1019
      2EN and TGx 1497-1D) which were part of a larger collection evaluated in
      agronomic field trials in Nigeria were selected for characterization of
      physicochemical properties, chemical composition, water absorption, cooking time
      and cooked texture as a function of soaking and cooking. Seed density, leached
      solids, swelling capacity and seed coat percentage were within a range of 1.15 to
      1.26 g per ml, 1.00 to 1.26 g per 100 g, 80.25 to 84.35 g per 100 g and 6.6 to
      10.1% w/w of dry beans, respectively. The total polyphenol content of the cream
      colored beans was similar (0.75 to 0.76 mg/g) but higher than the amount (0.60
      mg/g) found in the white beans. Cooking times varied between 71 and 96 min
      without soaking and were reduced by about 32.0% following a presoaking treatment
      in water for 12 hours at room temperature (28 +/- 1 degrees C). Small seeds
      absorbed higher amounts of water during soaking and required less cooking time
      than larger seeds. Unsoaked beans required 40 min of cooking to achieve the same
      degree of cooked texture as the soaked beans cooked for 20 min, suggesting that
      cooking times and cooked texture for all lines were improved through soaking.

PMID- 9198112
TI  - Composition and functional properties of unprocessed and locally processed seeds
      from three underutilized food sources in Nigeria.
AB  - Chemical and functional properties of unprocessed (raw) and locally processed
      seeds of Brachystegia eurycoma, Detarium microcarpum and Mucuna sloanei that
      affect their utilization as sources of human food were investigated. The seeds,
      which are underutilized food sources in Nigeria, were subjected to local
      processing methods which included roasting, boiling, dehulling/shelling, soaking
      and the changes in composition and functional properties were estimated. Chemical
      analyses showed that the crude protein contents of the raw seeds ranged from 12.2
      to 23.2%; fat varied from 4.9 to 12.0%. The level of phytic acid in the raw seeds
      (192.4-215 mg/100 g) was observed to be lower than the levels found in some
      commonly consumed pulses in Nigeria. There were no significant differences (p >
      0.05) between crude protein contents and the least gelation concentrations of the
      raw and processed samples, but processing (roasting, boiling, dehulling and
      soaking) significantly (p = 0.011) improved in vitro protein digestibility, water
      and fat absorption capacity and decreased the bulk density, nitrogen solubility
      and the phytic acid and polyphenol contents of the samples. Processed samples had
      high water (3.4-3.8 g/g) and fat (1.8-2.1 g/g) absorption capacities and hence
      may be useful as functional agents in fabricated foods such as bakery products
      and ground meat formulations.

PMID- 9198113
TI  - Chemical composition and content of antinutritional factors in Polish cultivars
      of peas.
AB  - The seeds of 15 Polish pea varieties contained from 221 to 281 g/kg crude protein
      with a mean of 240.2 +/- 3.5 g/kg dry matter (DM). The weight of 1000 pea seeds,
      depending on cultivar, ranged from 209.4 to 280.4 g. No interactive effect
      between the seed mass and the crude protein content was detected. The highest
      significant negative correlation between weight of seeds and dietary fiber
      content was r = -0.815XX. The content of dietary fiber ranged from 161.5 to 209.9
      g/kg with a mean of 187.9 +/- 3.8 g/kg. The mean gross energy of seeds was 18.1
      +/- 0.28 MJ/kg. Amino acid composition of all the cultivars was similar, which
      was indicated by a similar index of essential amino acids (EAAI) of about 69.7 +/
      0.25. Trypsin inhibitor content in seeds was from 2.83 to 7.32 TIU/mg and the
      content of phytates ranged from 6.32 to 13.36 mg/g DM. The mean content of
      polyphenols and flavanols in analysed pea cultivars was 0.92 and 0.46 mg/g,
      respectively. In the seeds of most cultivars little or no pyrimidine glucosides,
      i.e. vicine and convicine, were found. The overall mean oligosaccharide content
      was 64.3 +/- 1.8 g/kg, of which alpha-galactosides were 46.8 +/- 2.0 g/kg. The
      antinutritional factor content was not significantly correlated with protein
      content. No statistical relationship was found between crude protein and dietary
      fiber content. It was observed that pea cultivars with higher trypsin inhibitor
      activity contained significantly less flavanols (r = -0.607X) and alpha
      galactosides (r = -0.617X). The varieties with higher seed content of dietary
      fiber contained the highest amount of alpha-galactosides (r = 0.514X).

PMID- 9198114
TI  - Tissue-specific enhancement of xenobiotic detoxification enzymes in mice by
      dietary rosemary extract.
AB  - Plant foods contain nutritive and minor, nonnutritive components capable of
      inhibiting experimental carcinogenesis. Many of these cancer-protective extracts
      act by enhancing the activities of enzymes that can detoxify reactive substances.
      In the present study an extract of the spice plant rosemary was fed at
      concentrations of 0.3% and 0.6% (by weight) for 4 weeks to female A/J mice prior
      to determination of the activities of the detoxification enzymes glutathione-S
      transferase (GST) and NAD(P)H: quinone reductase (QR) in lung, liver and stomach.
      Liver activities of GST and QR, and stomach GST activity were significantly
      increased in animals fed diets containing rosemary extract. However, diets
      supplemented with rosemary extract did not affect lung GST and QR activities.
      These results indicate that components of rosemary extract have the potential to
      protect mouse liver and stomach from carcinogenic or toxic agents.

PMID- 9198115
TI  - Chemical and biological evaluation of proteins and mucilages from roots and seeds
      of Glossostemon bruguieri Desf. (Moghat).
AB  - The powdered roots of moghat (Glossostemon bruguieri) have been traditionally
      used in Eastern countries for their nutritive and therapeutic value. However, the
      biological effects of the plant constituents have not been proved on the basis of
      scientific research. The present study aimed to evaluate the content and
      composition of proteins and mucilages of the roots and seeds of moghat, as well
      as the hypoglycemic effect of the mucilages. The crude protein constituted 19.5%
      of the seeds, while it made up 4.5% of the peeled dried roots of Glossostemon
      bruguieri (Moghat). Glutamic acid, proline, leucine, phenylalanine, histidine and
      arginine were abundant in the protein of both plant parts; 72 and 83%,
      respectively. Valine, cysteine, methionine and lysine were detected only in seed
      protein. Molecular weights of the seed proteins were 50,000, 45,000 and 22,000.
      Moghat seeds contained 5.0% mucilage, while 15.75% and 29.60% were recorded in
      roots of one- and two-year-old plants, respectively. GLC investigation showed
      that both these plant parts contained rhamnose, xylose, mannose and galacturonic
      acid. Arabinose (1.8%) and glucuronic acid (14.6%) were present only in the
      seeds, while galactose constituted 33.7 to 34.5% of the root mucilage. Age of the
      roots was reflected in quantitative differences rather than qualitative ones. The
      root mucilages had remarkable hypoglycemic activity, decreasing the blood glucose
      level in diabetic rats by 54.5% within 15 days. Accordingly, moghat roots should
      be investigated as potential medical and nutritive food.

PMID- 9198116
TI  - Effect of pH and temperature on the immunogenicity of glycinin (Glycine max L.).
AB  - Sensitive immunologic techniques for the detection of alterations that occur in
      protein antigens were used to evaluate the immunogenicity of soybean glycinin
      after isolation, heat denaturation and pH alteration. The objective was to
      determine the effect of these agents on the immunogenic ability of this protein
      fraction. Immunologic assays performed on heat-denatured glycinin up to 80
      degrees C in the presence of antinative glycinin serum demonstrated that glycinin
      retains its immunogenic properties. Above 90 degrees C this biological property
      begins to disappear, with protein insolubilization and epitope modification due
      to the conformational changes imposed by temperature. A reduction in
      immunogenicity also occurred when glycinin was taken to pH 2.0 (below its pl) and
      pH 11.00 (above its pl) and exposed to high temperatures in the presence of
      native antiglycinin serum. From these data one can conclude that, at extreme pH
      values, intramolecular reactions may occur which, in combination with the
      structural disorganization caused by high temperatures, may contribute to the
      reduction of immunogenicity.

PMID- 9198117
TI  - Effect of coconut palm wine (Toddy) on carbohydrate metabolism in pregnant rats
      and fetuses.
AB  - The objective of this study was to determine the effects of an alcoholic beverage
      (Toddy) and the equivalent quantity of ethanol on carbohydrate metabolism in
      utero. Female rats were exposed to Toddy from coconut palm (24.5 ml/kg body
      weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before
      conception and throughout gestation. On the 19th day of gestation, hypoglycemia
      was seen in both the treated groups, but it was more in the Toddy-treated group.
      Synthesis of glycogen was elevated on exposure to ethanol/Toddy but its
      degradation was enhanced only in alcohol-exposed rats. Key enzymes of citric acid
      cycle and gluconeogenesis were inhibited on administration of both alcohol and
      Toddy. Activity of glycolytic enzymes were increased. Toddy seemed to potentiate
      the toxicity induced by alcohol, indicating the additive effects of congeners.

PMID- 9198118
TI  - Effect of selected Egyptian cooking methods on faba bean nutritive value and
      dietary protein utilization 2: ability of faba bean products to support
      hemoglobin response in rats.
AB  - To evaluate the dietary protein utilization and iron deficiency anemia as
      affected by the faba bean nutrient intake, a bioassay with rats was carried out
      with different experimental diets containing four faba bean products (stewed
      beans 'Medammis', deep fried dough 'Falafel', boiled germinated beans 'Nabet
      Soup' and poured paste 'Bissara') widely consumed in the Middle East. Amino acid
      composition of all faba bean products was determined and compared to raw beans.
      Severe heat-processing markedly decreased some essential amino acids, especially
      phenylalanine, cystine, methionine and tryptophan. Protein scores were 24.6,
      19.5, 29.2, 28.2 and 35.6 for raw faba beans, 'Medammis', 'Falafel', 'Nabet Soup'
      and 'Bissara', respectively. 'Bissara' possessed the highest nutritional value,
      since it had the lowest GDR value [Grams consumed of product to cover the daily
      requirements for adult man in protein (63 g) and in energy (2900 kcal)] for the
      limiting amino acids (L A A). As indicated by P S/150 values [Satisfaction of the
      daily requirements of the adult man when 150 g (one can content) are consumed of
      product] for L A A, i.e. methionine+cystine (lowest P S/150 value), the above
      mentioned faba bean products cover about 53, 77, 77 and 97% of the daily
      requirements of adult man in L A A, respectively. Fecal nitrogen excretion
      increased and true nitrogen digestibility decreased significantly (p < 0.01) with
      the inclusion of 'Medammis' in the diet. 'Nabet Soup' exhibited the highest true
      nitrogen digestibility. In contrast, the biological value of nitrogen was
      apparently unaffected. Highest blood hemoglobin level was found in rats fed diets
      containing 'Bissara', 'Falafel' and 'Nabet Soup', whereas the addition of
      'Medammis' in the diet induced a significant (p < 0.05) reduction in blood
      hemoglobin level of fed rats.

PMID- 9198119
TI  - Thrombosis in the young: epidemiology and risk factors. A focus on venous
      thrombosis.
AB  - Thrombosis occurs most often as myocardial infarction, cerebral infarction or
      venous thromboembolism, ie, deep-vein thrombosis and pulmonary embolism. The
      incidence of all types of thrombosis is strongly dependent on age. Among young
      individuals, up to age 40, venous thrombosis is the most common form of
      thrombosis. The risk factors for arterial and venous thrombosis differ, and among
      the latter disorders of hemostasis appear to be more prominent. In children
      venous thrombosis appears almost exclusively in association with venous
      catheters, with an exception of the renal vein thrombosis of the newborn, which
      has an unknown etiology. In young adults, the risk factors for venous thrombosis
      are essentially the same as in older individuals, excepting oral contraceptives,
      pregnancy and puerperium which are limited to young women. In young women, most
      venous thrombotic events can be attributed to oral contraceptives. Venous
      thrombosis is a multicausal disease: more than one risk factor needs to be
      present before thrombosis occurs. The younger an individual, the more risk
      factors are required to precipitate thrombosis: in children often three or four,
      and in young adults often two or more.

PMID- 9198120
TI  - Thrombosis in the young: effect of atherosclerotic risk factors on the risk of
      myocardial infarction associated with prothrombotic factors.
AB  - Myocardial infarction in the young provides a unique model for the investigation
      of potential interactions between atherosclerotic and prothrombotic risk factors.
      Because myocardial infarction reflects atherothrombotic disease, it is important
      to take into account factors related to atherosclerosis when examining
      prothrombotic factors as potential determinants of myocardial infarction. In
      Western societies, there are increases in both the prevalences of metabolic risk
      factors and atherosclerotic coronary disease with aging. The clinical expression
      of the thrombotic risk associated with heritable factors, such as factor V
      Leiden, as myocardial infarction appears to occur only in the presence of other
      risk factors, such as smoking and known metabolic risk factors related to
      atherosclerosis. If confirmed in other studies of factor V Leiden and with other
      mutations related to prothrombotic risk, these observations will likely have both
      etiologic and practical consequences. Finally, we suggest that efforts to
      determine whether a prothrombotic risk factor contributes "independently" to the
      risk of myocardial infarction may lead to a significant underestimation of the
      importance of the factor in the occurrence of myocardial infarction, particularly
      among clinically-important subsets of the population.

PMID- 9198121
TI  - Cerebrovascular disease in young patients.

PMID- 9198122
TI  - Viral vector-mediated gene therapy for hemophilia B.
AB  - Over the past five years, significant advances have been made in the development
      of novel viral vector systems for the treatment of hemophilia B by somatic gene
      therapy. At present, both a sustained but partial or a complete but transient
      correction of the hemophilia B phenotype have been observed in a clinically
      relevant animal model. Present efforts are being directed toward the development
      of safe, effective and persistent methods of virally-mediated gene transfer to
      achieve the complete restoration of normal hemostasis in individuals with
      hemophilia B.

PMID- 9198123
TI  - Gene therapy for hemophilia A.
AB  - Significant progress has been made on the development of gene therapy for the
      treatment of hemophilia A, a common bleeding disorder caused by subnormal levels
      of blood coagulation factor VIII (FVIII). Recent advances in gene transfer
      technology have enabled the expression of therapeutic to physiological levels of
      human FVIII in normal animals as well as hemophiliac mice and dogs. However, the
      in vivo persistence of FVIII expression was variable, ranging from one day to
      over five months. Despite recent advances in the development of hemophilia A gene
      transfer vectors, each still faces limitations to its clinical utility. Current
      research is focused on improving gene transfer vehicles and delivery methods to
      enable sustained clotting factor expression, treatment readministration, and
      circumvention of the host immune response to the treatment.

PMID- 9198125
TI  - Clinical studies with megakaryocyte growth and development factor (Mpl-ligand).
AB  - The haemopoietic growth factor mpl-ligand (also known as thrombopoietin, and
      Megakaryocyte Growth and Development Factor [MGDF] is a recently cloned and
      characterized megakaryocyte-active factor. Administration of MGDF to humans was
      associated with a dose-related increase in the platelet count with maximum levels
      observed between days 12-18. Platelets had normal appearance and functioned
      normally in assays of platelet aggregation and ATP-release. There was no evidence
      of platelet activation as assessed by platelet surface markers. The earliest
      detectable effect of MGDF was an increase in early (reticulated) platelets by day
      3-4. MGDF also hastened recovery from thrombocytopenia when given after
      myelosuppressive chemotherapy. MGDF caused mobilisation into the blood of
      progenitor cells of multiple haemopoietic lineages, and was synergistic with G
      CSF in this action after chemotherapy. MGDF was well tolerated with no adverse
      effects directly attributable to its administration. Further clinical evaluation
      is on-going.

PMID- 9198124
TI  - Thrombopoietin (Mpl-ligand) and the regulation of platelet production.
AB  - Thrombopoietin is the primary physiological regulator of platelet production. TPO
      stimulates both early and late megakaryocyte (MK) progenitors, and acts
      additively or synergistically with several cytokines on various progenitors
      including the most primitive stem cells. Much has been learn about the physiology
      of the endogenous TPO production and its regulation. TPO is constantly produced
      by the liver and kidney; its plasmatic clearance occurs by binding to the Mpl
      receptor expressed on MKs and platelets. TPO binding is followed by
      internalization and catabolism. The factor is a potent thrombopoietic agent in
      vivo and accelerates platelet recovery in several models of marrow suppression.
      Phase I clinical trials have begun. The lack of adverse effects suggests that TPO
      may join other cytokines in the clinical armamentarium. Nevertheless, several
      important areas of basic or clinical haematology remain to be explored to fully
      understand the biology of this new cytokine. For example, is TPO needed for the
      terminal stage of platelet formation? What genetic events are involved in the
      process of endomitosis? What are the physiopathological mechanisms underlying
      thrombocytopenia or thrombocytemia in human?

PMID- 9198126
TI  - Prediction of postoperative deep-vein thrombosis.
AB  - Prediction of patients at sufficiently high risk of postoperative deep vein
      thrombosis (DVT) to indicate perioperative antithrombotic prophylaxis usually
      employs only clinical risk factors. Studies of preoperative and/or postoperative
      haemostatic tests in the prediction of postoperative DVT are reviewed. In
      general, the results support the biological concept of a preoperative and
      postoperative prothrombotic tendency in patients who develop DVT. However, the
      clinical utility of such tests is unproven; so at present they cannot be
      advocated for routine preoperative or postoperative screening.

PMID- 9198127
TI  - Fibrinolytic and inflammatory markers for arterial occlusion: the evolving
      epidemiology of thrombosis and hemostasis.

PMID- 9198128
TI  - Insights into selectin function from knockout mice.
AB  - The development of animal models through gene targeting was very useful to the
      selectin field. Selectins are found on endothelium, platelets and leukocytes and,
      they mediate adhesion among these cell types. The removal of a single selectin
      gene taught us that P-selectin on the vessel wall mediates leukocyte rolling in
      the absence of inflammation and that all three selectins contribute to leukocyte
      rolling during inflammation. Similarly, P-selectin is responsible for early
      neutrophil recruitment while the other selectins contribute in later stages. The
      knockout animals also confirmed the important role of L-selectin in lymphocyte
      homing. Removal of both endothelial selectins uncovered the hidden importance of
      E-selectin in leukocyte homeostasis and showed that the endothelial selectins
      were as important for leukocyte extravasation as the leukocyte beta 2 integrins.
      The submission of selectin-deficient mice to models of various human diseases can
      provide invaluable information on conditions in which an anti-selectin therapy
      may prove beneficial.

PMID- 9198129
TI  - Vascular biology of CD36: roles of this new adhesion molecule family in different
      disease states.
AB  - The human CD36 antigen is a scavenger receptor and a celladhesion molecule
      expressed by platelets, monocytes and microvascular endothelial cells, among
      other cell types. It belongs to a new and growing family of integral membrane
      glycoproteins that recognize a wide range of ligands. CD36 has been implicated in
      hemostasis, thrombosis, malaria, inflammation, lipid metabolism and
      atherogenesis. Recently, significant advances in CD36 biology have been reported
      and new CD36-like proteins have been identified.

PMID- 9198130
TI  - The protein C pathway: new insights.

PMID- 9198131
TI  - Antiphospholipid antibodies: predictive value of laboratory tests.
AB  - aPL antibodies are a wide and heterogeneous family of autoantibodies, formerly
      believed to be directed at anionic phospholipids. In recent years they have been
      shown to be directed at plasma proteins bound to suitable (phospholipid) anionic
      surface: beta 2-GPI and prothrombin are the best known and characterized
      antigens, which are recognized by aCL antibodies and most Lupus Anticoagulants,
      respectively. The presence of these antibodies has been associated with arterial
      and venous thrombosis, recurrent miscarriages and thrombocytopenia in the so
      called "Antiphospholipid Syndrome". Retrospective and "cross-sectional" studies
      have established the role of aCL antibodies and Lupus Anticoagulants as risk
      factors for both venous and arterial thrombosis, the most common clinical
      manifestations of APS. Prospective studies performed in different patients'
      populations have validated the association between aCL antibodies and Lupus
      Anticoagulants with venous and, possibly, arterial thrombosis. Along with the
      concept of the heterogenity of aPL antibodies there is the observation that among
      Lupus Anticoagulants aCL-type A, but not LA antibodies, appear to represent a
      risk factor for thrombosis. However, informations on the predictive value of the
      various laboratory tests with respect to thrombosis are still rather limited. It
      is, therefore, necessary to continue the development and standardization of
      assays that selectively identify aPL antibodies associated with an increased risk
      of thrombosis, in order to help the clinicians to establish the most appropriate
      therapeutic strategies for the prevention of the thromboembolic complication of
      APS.

PMID- 9198132
TI  - Thrombogenic mechanisms of antiphospholipid antibodies.
AB  - These studies indicate how immunoglobulin populations that react with
      phospholipid surfaces in the absence of other cofactor molecules can selectively
      inhibit anticoagulant pathways and lead to a prothrombotic state. These studies
      combined with those of others indicating the presence of a-PE antibodies (often
      in isolation) in thrombotic patients illustrate the need to better define the
      assays to determine patients at risk. Neither the LA assays nor the anti
      cardiolipin assays presently in use may be testing for the population(s) of
      clinical importance. A better understanding of the biochemical requirements of
      the various reactions involved should help the rational design of such assays.
      The preliminary studies of Salmon, et al, also show that the genetic context of
      the patient may contribute to the thrombotic mechanism of any APA present. It is
      unlikely any single mechanism is responsible for the thrombogenic activity of all
      APAs associated with thrombosis and this will be a fertile field of investigation
      for a significant time to come.

PMID- 9198133
TI  - Targeted mutations in integrins and their ligands: their implications for
      vascular biology.

PMID- 9198134
TI  - Molecular crosstalk between adhesion receptors and proteolytic cascades in
      vascular remodelling.
AB  - The multifunctionality of adhesion receptor ligands as well as the promiscuous
      nature of vascular integrins and nonintegrin-dependent adhesive interactions
      allow ligand-receptor binding of variable strength. The cooperation with
      pericellular proteolysis cascades is required for vascular remodelling during
      angiogenesis, atherogenesis or inflammatory processes. In particular, integrin
      dependent cell contact, spreading and (trans-)migration can be modulated by ECM
      associated PAI-1 and uPA-receptor driven reactions that are intimately linked to
      the invasive potential of cells. Recently, mechanisms of molecular crosstalk
      between these receptor systems have been recognized: (a) uPA-receptor may
      directly interact with beta 1- and beta 2-integrins on circulating blood cells;
      (b) av beta 3-integrin-directly binds to a matrix metalloproteinase; (c) uPA and
      PAI-1 balance the high affinity binding of vitronectin to uPA-receptor; (d)
      vitronectin-dependent cell adhesion and migration involving alpha v-integrins or
      uPA-receptor are blocked by active PAI-1 independent of its role as protease
      inhibitor. These results are compatible with vascular injury studies in uPA- and
      PAI-1 knock-out mice and provide new targets for the treatment of diseases
      associated with imbalanced vascular remodelling.

PMID- 9198135
TI  - Integrin alpha IIb beta 3 and platelet function.

PMID- 9198136
TI  - Contact activation: a revision.
AB  - In conclusion, a revised view of the contact system has been presented. This
      system has little to do with the initiation of hemostasis. Like lupus
      anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be
      risk factors for thrombosis. BK from kininogens is a potent modulator of vascular
      biology inducing vasodilation, tissue plasminogen activator release, and
      prostacyclin liberation. Kininogens, themselves, are selective inhibitors of
      alpha-thrombin-induced platelet activation preventing alpha-thrombin from
      cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha
      thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's
      breakdown products. HK also is the pivotal protein for contact protein assembly
      on endothelium. It is the receptor for prekallikrein which when bound to HK
      becomes activated to kallikrein by an endothelial cell enzyme system independent
      of activated forms of plasma factor XII. Prekallikrein activation on endothelial
      cells results in kinetically favorable single chain urokinase and plasminogen
      activation. Thus the "physiologic, negatively charged surface" for contact system
      activation is really the assembly of these proteins on cell membranes and
      activation by membrane-associated enzymes.

PMID- 9198137
TI  - Activation of the factor VII-tissue factor pathway.
AB  - Advances in our knowledge of the biochemistry of coagulation have facilitated the
      development of sensitive and specific assays that are able to detect the
      generation of coagulation enzymes in vivo. It has been demonstrated that the
      factor VII-tissue factor pathway functions under normal conditions to generate
      factor Xa and convert prothrombin to thrombin. Furthermore, the factor VII-tissue
      factor pathway is also mainly responsible for the activation of factor IX with
      minimal contribution from the contact phase. However the relatively high levels
      of factor IXa generated are unable to convert factor X to factor Xa under basal
      conditions. Prospective studies are required to determine whether "biochemically"
      hypercoagulable individuals (i.e., those with elevated levels of free factor
      VIIa, activation peptides of factor IX, factor X, or prothrombin) are more likely
      to develop arterial or venous thrombosis.

PMID- 9198138
TI  - Factor VIIa-tissue factor: functional importance of protein-membrane
      interactions.
AB  - The first enzyme in the blood clotting cascade consists of two distinct protein
      subunits: a catalytic subunit (factor VIIa; FVIIa) and an essential regulatory
      subunit (tissue factor; TF). FVIIa is a soluble plasma protease, while TF is a
      cell-surface, integral-membrane protein. The recently reported X-ray crystal
      structure of the complex of FVIIa and the isolated extracellular domain of TF has
      provided important insights into the protein-protein interactions that bind these
      two subunits together (1). Equally important in the functioning of the TF-FVIIa
      complex, but much less well understood, are a series of protein-phospholipid
      interactions involving TF, FVIIa, and the natural substrates of this enzyme, as
      well as protein-protein interactions important in substrate recognition by TF
      FVIIa. Here we review recent studies on the membrane organization and role of
      protein-phospholipid interactions in the function of TF-FVIIa, the enzyme that
      triggers blood clotting in hemostasis and thrombosis.

PMID- 9198139
TI  - Venous thromboembolism and cancer: a two-way clinical association.
AB  - Venous thromboembolism and cancer are linked by a two way clinical association:
      venous thromboembolism may be the presenting feature of an occult cancer and
      patients with clinically overt cancer may develop a venous thromboembolic
      complication at any stage of their disease. Patients with venous thromboembolism
      in the absence of conventional risk factors have a 10% likelihood of having
      cancer. However, the value of investigating for underlying malignant disease in
      patients with idiopathic venous thrombosis who are otherwise well is still
      undefined: intensive diagnostic screening versus routine management is under
      evaluation in a randomised prospective clinical trial. Patients with cancer are
      at a high risk of developing postoperative venous thromboembolism. Therefore,
      they require prophylactic measures comparable to those usually recommended for
      major orthopaedic surgery. Both retrospective and prospective studies have
      recently focused attention on the thromboembolic risk associated with chemo-
      and/or hormone therapy in cancer patients. A prospective, double-blind,
      randomised study showed that very-low-dose warfarin is an effective and safe
      method for the prevention of thromboembolism in patients with metastatic breast
      cancer receiving chemotherapy. The evidence of lowered cancer mortality in
      patients receiving low molecular weight heparins has renewed interest in the
      antithrombotic agents as antineoplastic drugs. A multicentre study aimed at
      investigating this fascinating hypothesis is now being carried out.

PMID- 9198140
TI  - Newly diagnosed malignancy in patients with venous thromboembolism. Search or
      wait and see?
AB  - The incidence of newly diagnosed malignancy is increased in patients with
      unexplained venous thromboembolism during the first year after a thromboembolic
      event in comparison to controls (odds ratio, 3.9-36). Extensive screening with
      computed tomography, endoscopy and tumor markers can identify most of these
      undetected malignancies. However, approximately half of these can also be
      identified based on a simple clinical evaluation. Extensive screening has no
      demonstrated benefit and might actually cause harm. This consideration, combined
      with the economical and psychological costs of extensive screening leads to the
      decision not to use such screening procedures, unless indicated by clinical
      circumstances. Thus, it is appropriate to maintain a low threshold of suspicion
      for malignancy when treating patients with unexplained venous thromboembolism and
      to base the decision to perform additional diagnostic tests on the findings of an
      initial medical history, physical examination, routine laboratory tests and chest
      x-ray.

PMID- 9198141
TI  - Prevention of post-operative deep leg vein thrombosis in patients with cancer.

PMID- 9198142
TI  - Prevention of thrombotic disorders in cancer patients undergoing chemotherapy.
AB  - The etiology of thrombosis in malignancy is multi-factorial, and mechanisms
      include release of procoagulants by tumor cells, comorbid predisposing factors in
      anti-cancer drugs. The most reliable information on the incidence of
      thromboembolism in patients receiving chemotherapy comes from breast cancer. The
      rate of thrombosis in women with Stage II breast cancer receiving adjuvant
      chemotherapy is approximately 5%. The highest risk is in postmenopausal women and
      the addition of tamoxifen to chemotherapy increases the thrombotic risk over
      chemotherapy alone. The rate of thrombosis in metastatic breast cancer is likely
      to be much higher than that in Stage II breast cancer. Cancer patients with
      central venous catheters, e.g. Hickman, portacath, should receive 1 mg of
      warfarin daily. A recent trial has demonstrated that low molecular weight heparin
      can prevent catheter-related clots. There has been only one trial conducted
      evaluating prophylaxis in ambulatory cancer patients receiving chemotherapy. In
      this study, very low dose warfarin (INR 1.3-1.9) substantially reduced the risk
      of venous thromboembolism in breast cancer patients receiving chemotherapy.

PMID- 9198143
TI  - Efficacy and safety of oral anticoagulation in patients with cancer.
AB  - The treatment of venous thrombosis in patients with cancer is a common clinical
      problem. It appears that long term oral anticoagulant therapy with coumadin does
      not carry a significantly increased risk of major bleeding compared with the risk
      in patients without cancer. However, the risk of recurrent thrombosis in these
      individuals appears to be higher than in those patients without cancer.
      Nevertheless, the treatment of most patients with cancer and venous thrombosis
      with standard anticoagulant therapy is reasonable. Prospective, randomized trials
      are required to determine the optimal therapy for these patients, and, in
      particular, those that have failed traditional anticoagulation.

PMID- 9198144
TI  - Antithrombotic strategies in patients with cancer.
AB  - In recent years, a growing body of evidence has provided the convincing
      demonstration of a strong association between cancer and venous thromboembolism.
      Patients with cancer are at a remarkably higher risk of venous thromboembolism
      than patients free from malignant disorders during prolonged immobilization from
      any cause, and following surgical interventions. Standard heparin in adjusted
      doses or a low-molecular-weight heparin in doses commonly recommended for high
      risk surgical patients represent the prophylactic treatment of choice for cancer
      patients undergoing an extensive abdominal or pelvic intervention, Furthermore,
      the risk of thrombotic episodes is increased in cancer patients by chemotherapy
      and use of indwelling central venous catheters. Recent data suggest a positive
      benefit-to-risk ratio with the systematical use of fixed mini-dose of warfarin in
      both conditions. After experiencing an episode of thrombosis, cancer patients
      remain at risk of recurrence for as long as the cancer is active. Therefore, they
      should be protected by a long-term course of oral anticoagulation. The risk of
      recurrent thrombotic events despite adequate anticoagulation is markedly higher
      in patients with cancer than in those without cancer. The routine use of long
      term subcutaneous heparin for patients in whom warfarin has been ineffective. Can
      antithrombotic drugs improve survival in cancer patients? In cancer patients
      affected by deep-vein thrombosis, the treatment with low-molecular-weight
      heparins has been reported to lower mortality at a higher extent than the
      standard heparin therapy. Such an observation suggests that these agents might
      develop an antineoplastic activity.

PMID- 9198145
TI  - Molecular defects in rare bleeding disorders: hereditary haemorrhagic
      telangiectasia.
AB  - Vascular diseases may mimic coagulopathies by presenting as a haemorrhagic state.
      The archetypal example of an inherited disorder resulting in haemorrhage from
      dilated vessels of the microvasculature (telangiectasia) is Hereditary
      Haemorrhagic Telangiectasia (HHT, Rendu-Osler-Weber syndrome). This autosomal
      dominant disorder is characterised by haemorrhage from nasal, mucocutaneous and
      gastrointestinal telangiectasia, in addition to vascular anomalies in other
      organs, particularly in the pulmonary, hepatic and cerebral circulations. Linkage
      analyses have indicated there are at least three HHT loci, including the genes
      for endoglin on chromosome 9, and activin-like receptor kinase (ALK1) on
      chromosome 12. Mutations in these genes, together with recent data on the normal
      function of the encoded proteins highlight the role of TGF-b family members in
      the pathogenesis of HHT. Complimentary information from other telangiectatic
      states indicates potential precipitants, and indicate a critical role for TGF
      beta ligand-receptor interactions in vascular homeostasis.

PMID- 9198146
TI  - Inherited factor VII deficiency: molecular genetics and pathophysiology.

PMID- 9198147
TI  - Inherited factor X deficiency: molecular genetics and pathophysiology.

PMID- 9198148
TI  - Acute ischemic stroke and heparin treatments.
AB  - Several case-control studies have reported enhanced platelet activity,
      hypercoagulation and/or reduced fibrinolytic activity in patients with acute
      ischemic stroke. However, results of these studies are conflicting and do not
      allow to make recommendations regarding heparin treatment. The aim of heparin
      treatment in stroke patients is to prevent venous thromboembolic complications,
      to improve patient neurologic outcome, to reduce mortality and to prevent early
      recurrence. Unfortunately, only the first objective has been confirmed. As far as
      neurologic outcome and mortality are concerned, only trials performed since the
      CT era should be taken into account because the former ones did not rule out
      cerebral haemorrhages. The most recent clinical trials using LMWHs gave better
      results than the previous trials with UFH, but data are still conflicting and
      firm recommendations cannot be made until the results of ongoing megatriasl (such
      as IST) become available. As regards prevention of early recurrence, most authors
      agree that heparin is indicated in cardioembolic stroke.

PMID- 9198149
TI  - Antiplatelet therapy with aspirin in acute ischaemic stroke.
AB  - Antiplatelet therapy with aspirin, started within 48 hr of an acute ischaemic
      stroke, is safe and effective, avoiding about 10 deaths and early recurrent
      strokes per 1,000 patients treated. The reduction in early recurrent ischaemic
      stroke is not offset by any significant increase in intracranial haemorrhage.
      Immediate antiplatelet therapy in acute ischaemic stroke also seems to be
      associated with better long-term functional outcome, reducing the proportion of
      patients dead or dependent 6 months after the stroke. Aspirin is the only
      antiplatelet agent which has been evaluated adequately in acute ischaemic stroke.
      In this setting a dose is required which is large enough to achieve rapid
      inhibition of thromboxane biosynthesis and around 160-300 mg is required. If the
      patient can swallow safely, aspirin can be administered by mouth, if not, then
      per rectum as a suppository.

PMID- 9198150
TI  - Antithrombotic therapy of acute stroke: thrombolytic agents.
AB  - Following the initial report of the clinical use of plasminogen activators (PAs)
      in cerebrovascular thrombosis in 1958, interest in the efficacy of this approach
      accelerated only when the need for acute intervention in stroke was recognized.
      The use of PAs in acute ischemic stroke is based on the observation that
      approximately 80-90% of focal cerebral ischemic events presenting as strokes
      within 8 hr of symptom onset are due to atherothrombotic and embolic occlusions.

PMID- 9198151
TI  - Crossroads of L-arginine/arachidonate metabolism.

PMID- 9198152
TI  - Oxidized lipids in atherogenesis: formation, destruction and action.

PMID- 9198153
TI  - Tissue factor in the pathogenesis of atherosclerosis.
AB  - TF antigen and activity are found in abundance in human atherosclerotic plaques,
      particularly in the lipid-rich core. TF is also readily induced in the arterial
      wall by balloon injury and accumulates in the resulting neointima. In chronic
      atherosclerosis, the macrophage is likely to be the major source of TF within the
      plaque. TF accumulates as an early event associated with the migration of
      monocytes to the vessel wall in response to chemoattractants, such as MCP-1, and
      their differentiation into macrophages. As SMC become activated in the developing
      plaque, they provide a second source of TF. Macrophages and SMC accumulate lipid
      and become foam cells, ultimately degenerating into a necrotic core rich in TF.
      Spontaneous plaque rupture or acute interventions expose active TF in the core to
      circulating blood, triggering thrombosis. In acute arterial injury, SMC appear to
      be the chief source of TF. In normal vessels, the induction of TF in the medial
      SMC is not sufficient to generate fibrin, presumably because the TF is not
      readily accessible on the luminal surface. In contrast, endothelial denudation of
      previously injured arteries may expose intimal TF to circulating blood, resulting
      in rapid fibrin deposition. In advanced human atherosclerosis, it is likely that
      even in areas that do not contain "unstable" or "stable" plaques, the vessel wall
      is not normal and more closely resembles that of a previously injured artery
      possessing an active intima. Interventions, such as balloon angioplasty, coronary
      atherectomy, or stent placement may expose intimal TF, leading to fibrin
      deposition. As the initiator of coagulation, TF is a potential target for
      inhibiting the thrombotic complications of atherosclerosis. TFPI (reviewed in 52)
      is currently under clinical investigation as an anticoagulant and its effects on
      intimal hyperplasia in animal models are being studied. Direct factor Xa
      inhibitors, such as tick anticoagulant peptide (TAP) and leech anticoagulant
      peptide (ATS), are also under investigation (53-54). Finally, the recent
      crystallization of TF (55) and the TF:VIIa (56) should provide important new
      insights into the design of molecules for directly inhibiting TF.

PMID- 9198154
TI  - Platelet glycoprotein IIb/IIIa integrin blockade: recent clinical trials in
      interventional cardiology.

PMID- 9198155
TI  - Clinical trials with glycoprotein IIb/IIIa receptor antagonists in acute coronary
      syndromes.
AB  - Glycoprotein IIb/IIIa receptor antagonists are more potent platelet inhibitors
      than aspirin. Although important reductions in ischemic/thrombotic complications
      have been observed with these agents following coronary interventions, their
      potential value for the medical treatment of acute coronary syndromes is at
      present uncertain. The final results of large randomized studies in patients with
      acute coronary syndromes are eagerly awaited.

PMID- 9198156
TI  - Conjunctive use of platelet glycoprotein IIb/IIIa antagonists and thrombolytic
      therapy for acute myocardial infarction.

PMID- 9198157
TI  - Not just another pretty face: regulation of platelet function at the cytoplasmic
      face of integrin alpha IIb beta 3.
AB  - Integrin alpha IIb beta 3 is necessary for platelet thrombus formation by virtue
      of its ability to bind fibrinogen and von Willebrand factor in a regulated
      fashion and to mediate platelet aggregation. Moreover, alpha IIb beta 3
      transduces inward signals in response to ligand binding which promote
      cytoskeletal reorganization and other post-ligand binding events. Anchorage and
      signaling through alpha IIb beta 3 appear to be controlled by interactions of
      intracellular proteins with the cytoplasmic tails of alpha IIb and/or beta 3. The
      cytoplasmic tails and associated cytoskeletal components may function as a
      scaffold or nucleation site for the assembly of enzymes, substrates and adaptor
      molecules into a signaling complex. Identification of the components of this
      signaling complex and characterization of their dynamic interactions should lead
      to insights into the molecular basis of platelet activation defects and may
      provide a rationale for the development of new anti-thrombotic drugs.

PMID- 9198158
TI  - Phosphorylation and dephosphorylation mechanisms in platelet function: a tightly
      regulated balance.

PMID- 9198159
TI  - Protease-activated G protein-coupled receptors on human platelets and endothelial
      cells.
AB  - Extracellular proteases can trigger intracellular events via at least two members
      of the super-family of G protein coupled receptors: the thrombin receptor and PAR
      2. The two receptors have a similar structure, share a common mechanism of
      activation and may have arisen by gene duplication, but there are differences as
      well as similarities in their tissue distribution, the proteases by which they
      are activated and potentially in the consequences of their activation. Human
      platelets express the thrombin receptor, but not PAR-2, while at least some types
      of human endothelial cells express both. This review briefly summarizes current
      information about the two receptors and considers their roles in platelet and
      endothelial cell biology, their interactions with proteases, and the known
      mechanisms for receptor redistribution and replacement.

PMID- 9198160
TI  - Pathophysiology of platelet thrombin receptors.
AB  - The evidence is reviewed and a model presented for two distinct receptors being
      involved in platelet activation induced by alpha-thrombin: a high affinity
      thrombin receptor constituting approximately 50 copies of a supercomplexed form
      of GPIb coupled to phospholipase A2 and a moderate affinity receptor constituting
      approximately 2000 copies of the proteolytically activated, G protein-coupled
      seven transmembrane domain receptor coupled to phospholipase C. Reasons for the
      failure of certain studies to detect this role for GPIb are discussed.

PMID- 9198161
TI  - The unstable atherosclerotic plaque: clinical significance and therapeutic
      intervention.

PMID- 9198162
TI  - Second generation, B-domain deleted recombinant factor VIII.
AB  - A second generation recombinant factor VIII product has been developed and has
      been undergoing clinical trials since 1993. It is named r-VIII SQ and differs
      from other recombinant and plasma-derived products in that the B-domain of the
      molecule, to which no function has yet been ascribed has been deleted. It also
      has a formulation which does not include albumin. The specific activity is
      extremely high, 15,000 IU VIII:C/mg protein, and the stability of the
      reconstituted product is highly satisfactory. The pharmacokinetic properties are
      similar to those of a monoclonal purified, plasma-derived factor VIII. In
      clinical trials experience has been acquired from more than 87 previously treated
      patients on long-term treatment, 20 patients subjected to surgery and 72
      previously untreated patients. The record with regard to efficacy and safety is
      excellent but more experience is needed, especially regarding the risk of
      inhibitor development. The B-domain-deleted recombinant factor VIII has the
      potential to improve convenience and cost-benefit in haemophilia care. The safety
      margin regarding human viruses and other protein contaminants should be better
      with r-VIII SQ than with earlier products, which all contain far more human
      protein in their formulations.

PMID- 9198163
TI  - Recombinant factor IX.
AB  - Despite the introduction of recombinant preparations of factor VIII and
      recombinant factor VII and VIIa, patients with other forms of hemophilia,
      especially hemophilia B, have remained at increased risk for blood borne viruses
      because of a lack of clinically utilizable preparations of recombinant factor IX.
      This report describes the state of current tests with a recently licensed
      preparation of recombinant factor IX, BeneFix, from Genetics Institute.
      Structurally, functionally, and therapeutically, recombinant factor IX is
      comparable to monoclonal plasma-derived factor IX. The only observed difference
      between recombinant and plasma factor IX is the recovery in pharmacokinetic
      studies where recombinant factor IX recovery was approximately 72% that of a
      plasma factor IX product. This difference is attributed to be due to minor
      differences in the post-translational modification of recombinant factor IX
      compared to plasma. These studies demonstrate that recombinant factor IX is
      effective in the treatment of hemophilia B and has the safety profile expected
      from a product prepared by recombinant technology.

PMID- 9198165
TI  - Activation of ADP receptors and platelet function.

PMID- 9198164
TI  - Platelet GPIb-V-IX complex.

PMID- 9198166
TI  - Current status of activation markers in ischemic heart disease: markers of
      coagulation activation.

PMID- 9198167
TI  - Markers of platelet activation and oxidant stress in atherothrombotic disease.
AB  - Several new approaches to the study of platelet activation have been developed.
      Logically, these should be combined with novel indices of coagulant function
      (60,61) to select rational targets for antithrombotic drugs. They may also be
      invaluable in dose-finding, which has been a particular weakness in this area of
      drug development (62,63). While activation of platelets and the coagulation
      cascade are virtually simultaneous events, markers of the atherosclerosis are
      also artificially segregated from those of the complicating thrombotic process.
      Oxidant stress has been implicated in both platelet activation (64) and
      atherogenesis (65), yet our ability to study this system has been so constrained
      that we are unsure of appropriate doses of antioxidant vitamins. Novel approaches
      to this problem promise the ability to study oxidative modification of proteins
      (46,66,67), lipids (57) and DNA (45,68) in clinical studies.

PMID- 9198169
TI  - Thrombophilia as a multigenic disorder.

PMID- 9198168
TI  - Clinical impact of the plasminogen activation system in tumor invasion and
      metastasis: prognostic relevance and target for therapy.
AB  - Extravasation and intravasation of solid malignant tumors is controlled by
      attachment of tumor cells to components of the basement membrane and the
      extracellular matrix, by local proteolysis and tumor cell migration. Strong
      clinical and experimental evidence has accumulated that the tumor-associated
      serine protease plasmin, its activator uPA (urokinase-type plasminogen
      activator), the receptor uPA-R (CD87), and the inhibitors PAI-1 and PAI-2 are
      linked to cancer invasion and metastasis. In cancer, increase of uPA, uPA-R,
      and/or PAI-1 is associated with tumor progression and with shortened disease-free
      and/or overall survival in patients afflicted with malignant solid tumors. uPA
      and/or its inhibitor PAI-1 appear to be one of the strongest prognostic markers
      so far described. Strong prognostic value to predict disease recurrence and
      overall survival has been documented for patients with cancer of the breast,
      ovary, cervix, endometrium, stomach, colon, lung, bladder, kidney, brain, and
      soft-tissue. Due to the strong correlation between elevated uPA and/or PAI-1
      values in primary cancer tissues and the tumor invasion/ metastasis capacity of
      cancer cells, proteolytic factors have been selected as targets for therapy.
      Various very different approaches to interfere with the expression or reactivity
      of uPA or CD87 at the gene or protein level were successfully tested including
      antisense oligonucleotides, antibodies, enzyme inhibitors, and recombinant or
      synthetic uPA and uPA-R analogues.

PMID- 9198170
TI  - Molecular mechanisms of early inflammation.

PMID- 9198171
TI  - Leukocyte crosstalk at the vascular wall.
AB  - P-selectin is an adhesion molecule on platelets and endothelial cells that
      mediates the interaction of these cells with leukocytes. In addition to its
      docking function in cell-cell recognition, P-selectin is involved in cell
      signalling and cell communication. Upon platelet activation, P-selectin undergoes
      rapid phosphorylation and dephosphorylation. The biological role of these
      phosphorylation events within platelets is unknown. P-selectin, upon contact with
      its receptor on monocytes, initiates the de novo biosynthesis of tissue factor
      and other cytokines. Tissue factor upregulation on monocytes is mediated by PSGL
      1 and is independent of CD14, the LPS receptor.

PMID- 9198172
TI  - The role of leukocyte and endothelial adhesion molecules in ischemia-reperfusion
      injury.
AB  - Reperfusion of ischemic tissue is associated with an acute inflammatory response
      that may further exacerbate vascular and tissue damage. Compelling evidence from
      a variety of animal models indicates that neutrophils are the principle effector
      cells of the reperfusion injury and that blockade of neutrophil adhesion to
      endothelium attenuates ischemia-reperfusion injury. "Anti-adhesion" therapy may
      represent a new approach to treatment of the many diverse clinical disorders in
      which ischemia-reperfusion occurs.

PMID- 9198173
TI  - Effect of oral contraceptives on haemostasis variables.
AB  - Combined oral contraceptives (COCs) have effects on a large number of haemostasis
      variables. We have summarised literature data on effects of COCs containing 30-35
      micrograms ethinyl estradiol for the third generation of progestogens (PGs):
      desogestrel, gestodene and norgestimate. It is concluded that about 15 variables
      show a shift in distribution of the order of magnitude of their interindividual
      variation coefficient. When comparing the third generation of PGs with the second
      one (norgestrel, levonorgestrel) stronger increases are noted for the former for
      some haemostatic variables. Also differences between desogestrel and gestodene
      for factor VII were apparent. It indicates that the role of PGs in the effects of
      COCs is significant and their design may in addition to reduction of oestrogen
      dosage be important in reducing haemostatic complications. The survey on
      molecular and cellular mechanisms by which the sex steroids might operate showed
      a great lack of knowledge. Only for factor XII has a functional oestrogen
      response element in the DNA definitely been identified. The study of molecular
      markers of coagulation and fibrinolysis have shown a distinct increased
      activation of coagulation (F 1 + 2, FPA) and fibrinolysis (PAP), and an increased
      fibrin turn-over (increased FDPs); platelet products are not found increased
      (beta TG, PF-4). The increase in fibrinolysis represent a counterforce, but
      individual changes in variables in coagulation and fibrinolysis do not correlate
      indicating independent effects and no evidence for a individually regulated
      balance. A first step in further research might be in understanding the increase
      in coagulation activation (F 1 + 2) which has so far not been satisfactorily
      related to changes in blood concentrations of haemostatic factors and possibly
      local factors.

PMID- 9198174
TI  - Oral contraceptives and thrombotic disease: risk of venous thromboembolism.
AB  - Studies conducted in the first three decades after discovery of a link between
      venous thromboembolism and oral contraceptive users showed a relative risk of
      first thrombosis during oral contraceptive use of 2.9 (95% CI 0.5-17). In recent
      studies in which the sub-50 micrograms ethinyl estrodiol containing pills were
      investigated comparing current users with non-users, the RR is 3.8 for non-fatal
      deep VTE and 2.7 for superficial VTE, deep VTE and pulmonary embolism (PE)
      together and 2.1 for fatal VT and PE together. The association is attributed to
      the estrogenic component and not related to duration of pill use. The risk
      disappears once the pill has been stopped, and it is not elevated among past
      users. Smoking does not appear to be risk factor for VTE; obesity and varicose
      veins are, at the most, weak risk factors. Since a causal relationship between OC
      use and VTE is tempting, clues for unraveling the mechanism were sought in the
      hemostatic system. Studies of the coagulation system found changes in the
      activation of coagulation and fibrinolytic compartments, but within the normal
      range. An epidemiologic study showed that the risk of VTE among women using OCs
      is 30-fold increased by the presence of a mutation of factor V, called Factor V
      Leiden (5% prevalence in the Caucasian population). Selective screening for the
      mutated factor V should be limited to women with a personal or family history of
      VTE. Four epidemiologic studies showed a two-fold increase in risk of VTE with
      the use of OCs containing third-generation progestins (gestodene and
      desogestrel), relative to second-generations products (levonorgestrel). Biases
      cannot devaluate the conclusion that the increased risk of VTE in especially
      first-time and younger users of third-generation OCs is highly likely. The
      clinical consequence is therefore that second-generation OCs are the first choice
      in prescription to first-time users.

PMID- 9198175
TI  - Oral contraceptives and myocardial infarction: new evidence leaves unanswered
      questions.
AB  - Early epidemiological studies showed that current use of oral contraceptives was
      associated with a two-to four-fold increase in risk of myocardial infarction.
      More recent studies indicate that the risk has fallen and is probably below two
      fold, probably due both to changes in the formulations and to more cautious use
      of the preparations. There is inconclusive evidence of a small increase in risk
      associated with previous use of oral contraceptives. Myocardial infarction is
      rare in young women, particularly in the absence of clinical risk factors and
      cigarette smoking. It has been estimated that the population attributable risk is
      less than three events in one million women years. It has been suggested that
      preparations containing the newer progestogens, Desogestrel and Gestodene, are
      not associated with any increase in risk of myocardial infarction, but there is
      not yet sufficient evidence to test this hypothesis.

PMID- 9198177
TI  - Protein C deficiency: from gene defects to disease.
AB  - Genetic defects in the protein C pathway are associated with an increased risk
      for venous thrombosis. This review will focus on the nature of the defects in the
      protein C gene that underlie protein C deficiency and the relationship with
      thrombotic disease.

PMID- 9198176
TI  - Antithrombin: molecular basis of deficiency.
AB  - Antithrombin is a plasma protein regulator of coagulation proteinase activity,
      particularly that of thrombin. Its deficiency is a risk factor for venous
      thromboembolism. Considerable progress has been made in understanding the
      organisation and function of the antithrombin gene and protein, and the molecular
      basis of deficiency, all of which are reviewed, but briefly, here.

PMID- 9198178
TI  - Protein S deficiency.
AB  - The protein C (PC) pathway, with its cofactor protein S (PS), is an important
      natural antithrombotic mechanism. Patients with phenotypic PS deficiency may
      develop recurrent thrombosis during adulthood, with a probability of remaining
      free of thrombosis of about 50% at age 45. The molecular basis for hereditary PS
      deficiencies is highly heterogeneous, with a large spectrum of mutations that
      have various effects on the expression of the relevant allele.

PMID- 9198179
TI  - Direct thrombin inhibitors: appraisal of the antithrombotic/hemorrhagic balance.

PMID- 9198180
TI  - Clinical trials of direct thrombin inhibitors in acute ischaemic syndromes.
AB  - Unfractionated heparin is commonly used as standard therapy along with aspirin
      for the management of acute ischaemic syndromes. However, heparin has many
      limitations including a poor dose effect response and an inability to inactivate
      clot bound thrombin. Direct thrombin inhibitors inactivate clot bound thrombin
      and also prevent thrombin induced platelet aggregation. The prototypical direct
      thrombin inhibitor, hirudin, has been tested in the TIMI 9 and GUSTO II trials.
      These trials showed a 14% reduction in reinfarction at 30 days, but there was no
      effect on mortality or on the combined end point of death and nonfatal myocardial
      infarction (10.8% heparin versus 10.0% hirudin). More moderate bleeding occurred
      with hirudin than with intravenous heparin. Hirulog has been shown to increase
      the rate of TIMI grade 3 patency (from 35% to 48%, p = 0.03) at 90 minutes after
      streptokinase administration, and this is now being tested in a large mortality
      trial. Further trials are necessary to further test whether patient care can be
      improved by appropriate doses of these agents administered for an appropriate
      duration.

PMID- 9198181
TI  - Clinical trials of direct thrombin inhibitors during invasive procedures.

PMID- 9198182
TI  - Prevention of thromboembolic events in atrial fibrillation.
AB  - Nonvalvular atrial fibrillation is associated with an overall risk of stroke of
      4.5% per year. Advancing age, prior stroke or transcient cerebral ischemia,
      diabetes and hypertension are known risk factors. Ischemic stroke in patients
      with atrial fibrillation are generally more severe than ischemic stroke in
      patients with sinus rhythm. Warfarin is effective for primary and secondary
      prevention of ischemic stroke, reducing the risk by 68%. The effect of aspirin is
      still controversial, reducing the risk by 18-44%. Recent clinical trials have
      investigated the effect of warfarin given at a very low intensity either alone or
      combined with aspirin. The results from the SPAF III study demonstrated that a
      combination of mini-intensity warfarin plus aspirin was insufficient for stroke
      prevention in atrial fibrillation. Other trials now indicate, that oral
      anticoagulation at INR-values below 2.0 is not effective for stroke prevention in
      these patients. It is recommended that patients at high risk of stroke are
      treated with warfarin at an intensity of INR 2.0-3.0. Patients younger than 65
      without other risk factors can be given aspirin 325 mg/day. The present clinical
      challenge is to ensure effective and safe oral anticoagulation to patients with
      atrial fibrillation at high risk of stroke.

PMID- 9198183
TI  - Antithrombotic therapy following heart valve replacement.

PMID- 9198184
TI  - Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and
      fibrinolysis.
AB  - The thrombin thrombomodulin dependent activation of the plasma protein TAFI
      (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition of
      Fibrinolysis by the TAFIa is described. Work to date indicates that TAFIa is a
      carboxypeptidase B enzyme that suppress fibrinolysis most likely by down
      regulating the cofactor functions of partially degraded fibrin. The existence of
      TAFI provides the explanation for the apparent profibrinolytic effect of
      activated protein C. and implies the existence of an explicit molecular
      connection between the blood coagulation of fibrinolytic cascades that is
      expressed through the thrombin thrombomodulin dependent activation of TAFI. Thus,
      thrombin generation can, in principle, result in the suppression of fibrinolysis.

PMID- 9198185
TI  - Thrombomodulin structure and function.
AB  - Thrombomodulin is protein cofactor expressed on endothelial cell surfaces that
      modifies the substrate specificity of thrombin, apparently by an allosteric
      mechanism. The thrombin-thrombomodulin complex activates protein C, initiating an
      essential anticoagulant pathway. The cofactor function of membrane-associated
      thrombomodulin requires the last three of six tandemly repeated EGF-like domains
      (numbers 4, 5, and 6), as well as a Ser/Thr-rich spacer between EGF-like domain 6
      and the transmembrane domain. The Ser/Thr-rich domain is variably modified with a
      chondroitin sulfate chain that influences the affinity of thrombin binding and
      the calcium ion dependence of cofactor function. The structure of EGF-like domain
      4 has been determined by NMR spectroscopy, and the structure of a complex between
      thrombin and a peptide from thrombomodulin EGF-like domain 5 was determined by X
      ray crystallography. These structures are small steps toward an understanding of
      how thrombomodulin regulates thrombin.

PMID- 9198186
TI  - Thrombomodulin gene variations and thromboembolic disease.
AB  - Thrombomodulin (TM) is the endothelial cell cofactor for protein C activation.
      Since deficiencies of other protein C system proteins are known to cause
      thrombotic disease, then defects in the gene coding for TM could be responsible
      for inherited thrombophilia. We have searched for mutations in the TM gene among
      healthy controls as well as patients with thrombophilia and identified eight
      patients heterozygous for TM mutations that are distributed throughout the TM
      gene. We have shown that the respective TM mutation co-segregates with
      thromboembolic disease (TED) in four families. Moreover, we have demonstrated
      that the C allele in a common C/T dimorphism in the TM gene is significantly more
      frequent among survivors of premature myocardial infarction (MI) than in matched
      controls. We suggest that TM defects should be added to the list of risk factors
      in TED, and after further evaluation possibly be included in a routine laboratory
      evaluation of thrombophilia.

PMID- 9198187
TI  - The structural basis of function of the TF. VIIa complex in the cellular
      initiation of coagulation.
AB  - Cell surface tissue factor (TF), the major in vivo initiator of coagulation,
      activates coagulation by binding and allosteric activation of the serine protease
      factor. VIIa (VIIa). A graphic scheme to account for function of this initial
      bimolecular activation complex has emerged from the integration of structural
      with functional analyses. The VIIa light chain, specifically the Gla and EGF-1
      domains, form extended hydrophobic contacts with TF which account for most of the
      free energy of binding. These contacts tether VIIa and facilitate interactions of
      the protease domain with TF necessary for induction of protease function. Several
      contact residues in the VIIa protease domain-TF interface are involved in the
      activation of VIIa by complex allosteric effects. Macromolecular substrate
      zymogens interact with both the VIIa protease domain and the carboxyl-terminal
      module of TF. Docking of the VIIa Gla-domain to the latter region of TF appears
      to contribute to substrate assembly. The current data suggest an extended embrace
      between TF and VIIa to form the bimolecular enzyme TF.VIIa.

PMID- 9198188
TI  - Cytokine activation of endothelial cells: new molecules for an old paradigm.

PMID- 9198189
TI  - Cytokines: triggers of clinical thrombotic disease.

PMID- 9198190
TI  - Antibody-mediated thrombosis.

PMID- 9198191
TI  - Coagulation factor V: an old star shines again.
AB  - Blood coagulation factor V plays an important role in the regulation of thrombin
      formation. Activation of factor V by traces of activated coagulation factors
      (thrombin, factor Xa or meizothrombin) yields factor Va, the non-enzymatic
      cofactor of the prothrombinase complex. Since factor Va accelerates prothrombin
      activation under physiological conditions more than 10(4)-fold it is not
      surprising that down-regulation of factor Va cofactor activity by the protein C
      pathway is a very effective way for maintaining the hemostatic balance. In this
      paper we have reviewed the present status of structural knowledge of factor V and
      Va, the molecular changes in factor V that occur during factor V activation, the
      function of factor Va in prothrombin activation and the molecular mechanism of
      inactivation of factor Va by APC. Although considerable insight in the structure
      function relationship of factor V and Va has been achieved, the study of mutated
      factor V molecules obtained by recombinant DNA technology will undoubtedly
      resolve remaining questions. The latter is illustrated by the fact that the
      discovery of factor VaLeiden has significantly contributed to our present
      knowledge on the regulation of the cofactor activity of factor Va via the protein
      C pathway. It appears that modulation of the activity of APC by protein S and
      factor Xa will strongly affect the in vivo activity of this pathway. Factor V not
      only plays an important role in the regulation of the activity of the
      prothrombinase complex but also acts as cofactor in APC-mediated inactivation of
      factor VIIIa. This gives rise to a rather intricate mechanism of regulation of
      thrombin formation by APC that thus far has been mainly studied in model systems
      containing purified proteins. Thus, extensive studies in plasma will be required
      in order to get more insight in the in vivo regulation of thrombin formation via
      the protein C pathway.

PMID- 9198192
TI  - Platelet adhesion to collagen: an update.

PMID- 9198193
TI  - Platelet receptors for collagen.
AB  - The interaction of platelets with collagen is a complex reaction because collagen
      monomer does not have any affinity to platelets, but collagen fibrils and
      immobilized collagen bind strongly to platelets. It was postulated that a
      platelet would have multiple binding sites for collagen that would encompass
      several collagen molecules polymerized to each other. The mechanism for how these
      collagen fibrils or immobilized collagen bind to and activate platelets is still
      unknown. Two platelet glycoproteins, GP Ia/IIa (integrin alpha 2 beta 1) and GP
      VI, fulfill the following requirements for a physiological collagen receptor: 1)
      antibodies against these proteins inhibit the platelet aggregation induced by
      collagen and platelet adhesion to collagen under both static and flow conditions,
      and 2) patients whose platelets are deficient in either GP Ia/IIa or GP VI have
      been found, and their platelets show no interaction with collagen. Under flow
      conditions, which closely approximate physiological conditions under which
      thrombus formation occurs, platelets interact with vWf molecules bound to
      immobilized collagen and then the adhered platelets would react with collagen
      through their collagen receptors, resulting in activation of the platelets and
      subsequent formation of platelet aggregates. Although the details of the
      interaction of GP Ia/IIa with collagen have been investigated in recent years,
      the mechanism of the reaction between GP VI and collagen remains to be explored.

PMID- 9198194
TI  - The significance of subendothelial von Willebrand factor.
AB  - von Willebrand factor (vWf) serves to bridge between receptors on the platelet
      cytoplasmic membrane and the extracellular matrix. In addition to circulating in
      plasma, vWf is deposited into the extracellular matrix of the subendothelium
      where it is associated with type VI collagen microfibrils, but not with the
      elastin-associated microfibrils which are present in the deepest portion of the
      subendothelium at the zone of the internal elastic lamina. The reaction of
      platelets to type VI collagen in flow systems is qualitatively different from the
      shear rate dependent adhesion and aggregation response which is observed with
      fibrillar type I collagen, exhibiting a response only at low shear rates. The
      adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb
      IIIa complex. Platelets exposed to purified fibrillin-containing elastin
      associated microfibrils adhere and aggregate at low shear rates; this response
      appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the
      hypothesis that type VI collagen is a physiologically relevant binding site for
      vWf in subendothelium.

PMID- 9198195
TI  - Gene defects in 150 unrelated French cases with type 2 von Willebrand disease:
      from the patient to the gene. INSERM Network on Molecular Abnormalities in von
      Willebrand Disease.
AB  - Type 2 vWD is defined by qualitative defects of vWF and is subdivided into four
      subtypes: 2N, 2B, 2A and 2M. The characterization of 150 unrelated French cases
      with type 2 vWD emphasizes the heterogeneity of this group. In 51 cases of type
      2N vWD, new mutations were found not only in the D' domain (Cys25Tyr and
      Cys95Phe) but also in the D3 domain (Asp116Asn and Cys297Arg). In 42 cases of
      type 2B vWD, no new mutation was detected. In 45 cases with type 2A phenotype,
      three new candidate mutations were found in the A2 domain: Gln793Arg, Val841Phe
      and Leu876Pro. In addition, four new candidate mutations were detected in the A1
      domain: Cys509Gly, Arg545His, Arg552Cys and Cys695Tyr. Finally, five new
      candidate mutations were identified in 12 patients with 2M (or unclassified)
      phenotype: Leu513Pro, Gly561A1a, Glu596Lys, Arg611Leu and IIe662Phe. For all
      candidate mutations, expression studies are in progress. This study of a large
      number of French variants of vWD brings further insight into the relationship
      between phenotype and genotype.

PMID- 9198196
TI  - Gene-environment interaction in the determination of levels of haemostatic
      variables involved in thrombosis and fibrinolysis.
AB  - Functional sequence changes in the promoter of a gene may have a direct effect on
      the rate of transcription and thus on cellular or plasma levels of the protein.
      For both the beta fibrinogen gene and the plasminogen activator inhibitor-1 (PAI
      1) gene such functional variations have been described. For the fibrinogen gene a
      G/A sequence variation has been detected at position -455 of the promoter, with
      carriers of the A allele, representing roughly 20% of the population,
      consistently having 7-10% higher fibrinogen levels than those with the genotype
      G/G. For the PAI-1 gene we have detected a run of four or five Guanidine residues
      (4G/5G polymorphism), and in several published studies those homozygous for the
      4G allele (25% of the population) having levels of PAI-1 roughly 30% higher
      levels than 5G5G individuals. The magnitude of both of these genotype effects
      indicates that they are likely to be of biological significance in causing an
      elevated risk of thrombosis and reduced fibrinolysis. However the magnitude of
      these effects are modulated by several environmental factors and data will be
      presented to demonstrate interaction between genotype and presence of ischaemic
      disease and physical exercise, in the determination of an individual's plasma
      fibrinogen levels and of triglycerides and diabetes in determining levels of PAI
      1.

PMID- 9198197
TI  - Clinical relevance of polymorphic markers of arterial thrombosis.
AB  - Case-control and cross-sectional studies show that some common molecular
      variations (polymorphisms) of genes coding for proteins involved in
      atherosclerosis and thrombosis are often present in subjects who have experienced
      cerebrovascular or cardiovascular events. The clinical impact of the majority of
      polymorphic markers is disputed by prospective reports. In contrast, their
      pathophysiological implications and their role in monitoring parameters that are
      difficult to be checked by alternative means, are documented by the large
      majority of the reports. From the evidence available, there may be suggestion for
      further impact of polymorphic markers in vascular medicine. To substantiate this,
      new prospective studies that include individuals from different geographical
      areas and that take into account the statistical power, the informativeness of
      the markers, the coexistance of established risk factors and the genetic
      background of the populations analyzed, are urgently needed.

PMID- 9198198
TI  - Tissue factor pathway inhibitor: clinical deficiency states.

PMID- 9198199
TI  - Tissue factor pathway inhibitor: potential therapeutic applications.
AB  - Tissue factor pathway of coagulation plays a dominant role during normal
      haemostasis. Tissue factor pathway inhibitor (TFPI), expressed primarily by the
      microvascular endothelium, appears to be the major physiologic inhibitor of TF
      induced coagulation. TF-initiated coagulation also plays an important role in the
      pathophysiology of many diseases including coronary thrombosis, sepsis,
      disseminated intravascular coagulation, stroke, cancer, acute respiratory
      distress syndrome, and ischemia-reperfusion injury. Several animal studies have
      found a beneficial effect of anti-TF monoclonal antibodies and, recombinant TFPI
      in some of the above clinical conditions. rTFPI is presently being used in
      clinical trials in patients with sepsis and in those following microvascular
      surgery. This article discusses many of the animal studies addressing inhibition
      of TF-induced coagulation, as well as potential therapeutic uses of rTFPI in
      humans.

PMID- 9198200
TI  - Laboratory diagnosis of resistance to activated protein C (APC-resistance).

PMID- 9198201
TI  - Resistance to activated protein C caused by the factor VR506Q mutation is a
      common risk factor for venous thrombosis.
AB  - In 1993, inherited resistance to activated protein C (APC) was described as a
      novel risk factor for venous thrombosis. APC-resistance is present in 20-60% of
      venous thrombosis cases. It is caused by a single point mutation in the factor V
      gene which substitutes arginine (R) at position 506 with a glutamine (Q). The
      mutation is common in Caucasians with up to 15% prevalence in the population,
      whereas it is not found among other human races. Mutated factor V (FVR506Q,
      FV:Q506 or FV Leiden) is partially resistant to APC which results in a
      hypercoagulable state conferring a life-long increased risk of thrombosis.
      Individuals having FV:Q506 combined with other anticoagulant defects have a high
      risk of thrombosis, and it is now generally accepted that severe thrombophilia is
      a multigenetic disease. Easy functional and genetic tests for inherited APC
      resistance will profoundly influence the development of prophylactic regimens and
      hopefully result in a decreased incidence of thrombosis.

PMID- 9198202
TI  - The treatment of deep vein thrombosis and pulmonary embolism.
AB  - Deep vein thrombosis and pulmonary embolism can be considered as one clinical
      entity, termed venous thromboembolism, because of their comparable pathogenesis,
      treatment and prognosis. In this clinical spectrum of venous thromboembolism a
      gradient in severity of the disease can be recognized. Therapeutic strategies
      should be adapted to the extent of the thrombotic disease, varying from surgical
      or thrombolytic therapy in life-threatening disease to a watchful waiting
      diagnostic follow-up approach in minimal disease. In patients with established
      venous thromboembolism (low molecular weight) (LMWH), heparin should be
      initiated. An overview will be given of the safety and efficacy of the different
      therapeutic modalities such as thrombectomy, thrombolytic therapy, a watchful
      waiting diagnostic approach and unfractionated heparin. Furthermore, clinical
      studies comparing LMWH with unfractionated heparin in the initial treatment of
      venous thromboembolism will be reviewed.

PMID- 9198203
TI  - Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion.
AB  - Activated gelatinase A is reportedly associated with tumor spread. We identified
      a novel matrix metalloproteinase that localizes on the cell surface and mediate
      the activation of progelatinase A. Thus, this progelatinase A activator was named
      membrane-type matrix metalloproteinase (MT1-MMP). Following the first-discovery
      of MT1-MMP, two other MT-MMPs which can activate progelatinase A were identified
      (MT2- and MT3-MMP, respectively). Among these three MT-MMPs, MT1-MMP is most
      often overexpressed in malignant tumor tissues, including lung and stomach
      carcinomas that contain activated gelatinase A. This suggests that MT1-MMP is
      most closely associated with the activation of progelatinase A in these tumor
      tissues. The expression of MT1-MMP also induced binding of gelatinase A to the
      cell surface by functioning as a receptor. The cell surface localization of
      proteinases has advantages over pericellular proteolysis. MT1-MMP and its family
      may play a central role in the cell surface localization and activation of
      progelatinase A and via this mechanism, tumor cells use exogenous progelatinase A
      to mediate the proteolysis associated with invasion and metastasis.

PMID- 9198204
TI  - Comparative analysis of haemostatic proteinases: structural aspects of thrombin,
      factor Xa, factor IXa and protein C.

PMID- 9198205
TI  - The factor VIIa/tissue factor complex.
AB  - The tissue factor:factor VIIa (TF:F.VIIa) complex is the physiological initiator
      of blood coagulation and plays a role both in normal hemostasis and in various
      thrombotic disorders. The TF:F.VIIa crystal structure presented here shows the
      two molecules in association as a complex and provides a ready structural
      explantation for most of the complementary observations on the complex obtained
      by other techniques. This is only one F.VII structure of a series along the
      activation pathway going from zymogen F.VII, through F.VIIa alone, towards that
      in the ternary complex with a macromolecular substrate such as F.IX or F.X. To
      fully understand the activation of F.VIIa by TF will require further structural
      work, but in the meantime this structure may be used in the search for more
      effective and more specific anticoagulants.

PMID- 9198206
TI  - Structural mobility of antithrombin and its modulation by heparin.

PMID- 9198207
TI  - Hyperhomocysteinemia as a risk factor for arterial and venous disease. A review
      of evidence and relevance.
AB  - In homozygous homocystinuria due to cystathionine synthase deficiency,
      characterized by severe hyperhomocysteinemia, there is a high incidence of
      vascular complications. These observations focus on homocysteine as an
      atherogenic and thrombophilic agent. At the present time, there is also
      convincing evidence that even mild hyperhomocysteinemia is a risk factor for
      cardiovascular disease due to occlusive arterial complications. Furthermore, a
      positive association between mild hyperhomocysteinemia and the occurrence of
      venous thrombosis has been shown but needs further study. Mildly elevated
      homocysteine levels affect the arterial system independently from conventional
      risk factors. This newly- recognized factor seems equally strong in risk to
      hypercholesterolemia and smoking, while hypertension leads to a larger excess
      risk. It interacts synergistically with hypertension and smoking in a joint
      arteriosclerotic effect in patients with the concomitant presence of these risk
      factors. The homocysteine-lowering efficacy of a simple and safe vitamin regimen
      has been proven but data on the clinical outcome of such intervention are lacking
      thus far.

PMID- 9198208
TI  - Genetic predisposition to hyperhomocysteinemia: deficiency of
      methylenetetrahydrofolate reductase (MTHFR).

PMID- 9198209
TI  - Hyperhomocysteinemia and thrombosis: acquired conditions.
AB  - Hyperhomocysteinemia is a condition which, in the absence of kidney disease,
      indicates a disrupted sulfur amino acid metabolism, either because of vitamin
      (folate, B12 and B6) deficiency or a genetic defect. Epidemiological evidence
      suggests that mild hyperhomocysteinemia is associated with increased risk of
      arteriosclerotic disease and stroke. The relationship between
      hyperhomocysteinemia and thrombosis has been investigated in 10 studies involving
      a total of 1200 patients and 1200 controls. Eight of these studies demonstrated
      positive association with odds ratios that ranged from 2 to 13. This association
      was enhanced by including a methionine loading test. There is some evidence which
      suggests that hyperhomocysteinemia and APC resistance have a synergistic effect
      on the onset of thrombotic disease. Studies on the mechanism that underlies the
      relationship between thrombosis and hyperhomocysteinemia used non-physiologically
      high levels of homocysteine, rendering the data doubtful as to their patho
      physiological relevance.

PMID- 9198210
TI  - Vitamin K-dependent protein production in transgenic animals.
AB  - Vitamin K-dependent proteins are currently purified from pooled human plasma or
      produced in mammalian cell culture systems by recombinant DNA technology.
      Transgenic animals may provide an additional expression system for the production
      of these therapeutic proteins. Mice have been used to test hybrid genes which
      direct the expression of recombinant factor IX and Protein C to the mammary
      gland. Transgenic livestock have also been created that secrete into milk fully
      active Protein C at 0.3 mg/mL, and factor IX at 0.2 mg/mL. Thus, it is feasible
      to develop genetically manipulated livestock for the industrial production of
      vitamin K-dependent proteins.

PMID- 9198211
TI  - Current progress in the production of recombinant human fibrinogen in the milk of
      transgenic animals.
AB  - The mammary gland of transgenic animals has several advantages for production of
      heterologous proteins including a high cell density that results in high
      concentrations of secreted protein. While the mammary gland appears to be able to
      secrete fully assembled recombinant human fibrinogen (rhfib) at 0.1 to 5 g/l
      levels, some unassembled rhfib chains are also secreted. Presently, the
      relationship between unassembled rhfib and the coordinated translation of each
      nascent rhfib polypeptide in the mammary epithelia is unknown. The secretion of
      fully and partially assembled rhfib is widely variable among mammalian cell lines
      and where previously no cell line has been shown to secrete beta chain alone. We
      have observed that mammary epithelia can secrete B beta chain into milk as well
      as immature forms of other recombinant proteins, suggesting it likely uses a
      different secretory pathway than does the liver. This difference in secretory
      behavior is possibly due to the natural design of milk, where the precise
      regulation of post translational modifications and intracellular pools of nascent
      polypeptides needed to achieve fibrinogen assembly may be less important to
      fulfill the nutritional function of most milk proteins.

PMID- 9198212
TI  - The past, present and future of transgenic bioreactors.
AB  - Hybrid genes can control the tissue-specific synthesis of human proteins in
      transgenic animals. Thus, it is now possible to produce proteins of biomedical
      value in the body fluids or cells of transgenic livestock. In fact, the first
      transgenically produced protein, antithrombin III, is now in clinical trials and
      others will soon follow.

PMID- 9198213
TI  - How have trials of thrombolytics influenced clinical management of patients with
      acute myocardial infarction.

PMID- 9198214
TI  - Drug trials that have influenced our practice in the treatment of venous
      thromboembolism.
AB  - Heparin and oral anticoagulants have been the mainstay of antithrombotic therapy
      for the prevention and treatment of venous thromboembolism for over 50 years.
      Randomized trials have established their efficacy and have been used to refine
      the optimal dose and duration of therapy for different indications. Low-dose,
      subcutaneous, standard heparin and low molecular weight heparin (LMWH) provide
      effective primary prophylaxis, higher doses being indicated for patients who are
      at highest risk. OA is an alternative in high risk patients, particularly if
      there are persistent risk factors. Heparin and OA can be started concomitantly
      when treating patients with acute VTE. At least 4 days of adjusted dose standard
      heparin, or fixed dose LMWH, should be administered, and heparin should not be
      stopped until therapeutic OA is established. Acute DVT can be treated as an
      outpatient with fixed dose LMWH. In general, OA, with an International
      Normalization Ratio of 2.0-3.0, should be continued for 3 to 6 months. The
      optimal duration of OA may differ between patients who have VTE associated with a
      transient or a continuing (including "idiopathic") risk factors; however, this
      remains to be defined. New antithrombotic agents, such as direct thrombin
      inhibitors, are in the preliminary stages of evaluation for the prevention and
      treatment of VTE.

PMID- 9198215
TI  - The drug trials that have influenced our clinical practice in acute ischaemic
      stroke.
AB  - With the possible exception of aspirin, there are still no drug treatments which
      have been found to be so effective in randomised controlled trials, and meta
      analyses of such trials, that they should be used routinely in acute ischaemic
      stroke. The evidence on thrombolysis is tantalising but with only about 3500
      randomised patients in all the trials put together it is too early to say how,
      and for whom, this promising treatment should be used, particularly bearing in
      mind the risk of intracranial haemorrhage; the evidence so far is enough to
      persuade us to enter our patients into further large trials of thrombolysis but
      it is not enough to justify this treatment in our routine clinical practice.

PMID- 9198216
TI  - von Willebrand disease: from the bedside to therapy.
AB  - Von Willebrand's disease was recognized by a careful observant clinician.
      Research advances in blood banking technology and molecular biology, in addition
      to astute clinical observation, have led to unraveling the factor VIII molecule,
      classification of a heterogenous disease, and rational therapy.

PMID- 9198217
TI  - New treatments of von Willebrand disease: plasma derived von Willebrand factor
      concentrates.
AB  - During the past 10 years the quality of plasma derived virus inactivated products
      containing von Willebrand factor (vWF) has improved and the ratios of ristocetin
      cofactor activity (vWF:RCo) to von Willebrand factor antigen (vWF:Ag) have
      increased. There are, however, considerable variations in AHF-vWF products with
      ranges from 0.25 to 1.4 unit of vWF:RCo for each unit of vWF:Ag, and 0.5 to 5.3
      units of vWF:RCo for each factor VIIIC (FVIIIC) unit. The availability of a vWF
      product depleted of FVIII has allowed pharmacokinetic studies of the vWF protein.
      There have been no dose response studies, dosage regimens remain empirical and
      are still, except in rare instances, based on FVIIIC dosage. Current concentrates
      are as effective as cryoprecipitate in the management of patients with vWD non
      responsive to DDAVP. These concentrates should be preferred to cryoprecipitate
      which carries a risk of virus transmission.

PMID- 9198218
TI  - Recombinant von Willebrand factor.

PMID- 9198219
TI  - Modulation of thrombin's procoagulant and anticoagulant properties.
AB  - The procoagulant and anticoagulant functions of thrombin are controlled
      physiologically by allosteric changes induced by Na+ and vascular cell-surface
      TM. Key residues that mediate Na+ interaction with thrombin have been identified.
      Based on a site-directed mutagenesis approach, E229K thrombin is found to be the
      most optimal and potent PC activator with a marked shift in substrate specificity
      for PC over fibrinogen. E229K thrombin demonstrates significant anticoagulant and
      antithrombotic efficacy in animal models in vivo. Alternatively, a synthetic
      organic molecule (LY254603) has been discovered which interacts with thrombin and
      effectively modulates its functions in vitro. This new class of antithrombotic
      agents exploits the powerful natural PC anticoagulant pathway and may have a
      superior therapeutic profile than direct thrombin inhibitors.

PMID- 9198220
TI  - Signaling through G proteins in platelets: to the integrins and beyond.
AB  - Many of the agonists that cause platelet activation are thought to do so by
      interacting with G protein-coupled receptors on the platelet surface. By
      activating heterotrimeric G proteins, these receptors evoke shape change, granule
      secretion and platelet aggregation. This review provides a brief overview of
      these events, summarizes current information about the role of pleckstrin in
      events downstream from G protein-coupled receptors, and briefly considers the
      signaling pathways that couple G protein activation to the low molecular weight
      GTP-binding proteins which control cytoskeletal reorganization and fibrinogen
      receptor exposure during platelet activation.

PMID- 9198221
TI  - Thrombin, fibrin and platelets: a resonance loop in which von Willebrand factor
      is a necessary link.

PMID- 9198222
TI  - Structure and mechanism of action of the vitamin K-dependent gamma-glutamyl
      carboxylase: recent advances from mutagenesis studies.
AB  - The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the conversion of
      glutamic acid to gamma-carboxyglutamic acid in substrate proteins. The enzyme has
      recently been purified and the cDNA encoding the enzyme has been cloned. The
      availability of recombinant enzyme provides the opportunity to probe the
      mechanism of this unique enzyme. The binding sites for the gamma-carboxylation
      recognition site containing propeptide and carboxylatable glutamate residues of a
      vitamin K-dependent substrate protein have been localized to the amino-terminal
      250 residues of the enzyme. Regions of the carboxy-terminal of the enzyme are
      important for conversion of vitamin K hydroquinone to vitamin K epoxide, a
      reaction that occurs concomitantly with carboxylation and is catalyzed by the
      vitamin K-dependent carboxylase. Using pure recombinant vitamin K-dependent
      carboxylase it has been demonstrated that catalysis of vitamin K oxygenation by
      the enzyme is regulated by the availability of carboxylatable substrate.

PMID- 9198223
TI  - Characterization of the gamma-glutamyl carboxylase.
AB  - Studies on the vitamin K-dependent carboxylase are still in their infancy, but
      the cloning and purification of the enzyme have permitted a number of advances in
      our understanding of both the molecular biology, and mechanism of the
      carboxylase. Advances in our knowledge of the molecular biology of the
      carboxylase include chromosomal location, characterization of messenger RNA
      transcript(s) and the study of patients with carboxylase mutations. Our
      understanding of the mechanism of the carboxylase has been enhanced by the
      expression of peptides in E. coli which contain multiple carboxylation sites and
      more closely resemble the native carboxylase substrates. These peptides have been
      utilized to identify elements within the substrates which are critical for
      carboxylation and to demonstrate that the vitamin K-dependent carboxylase is one
      of the first examples of a processive post-translational modification enzyme.

PMID- 9198224
TI  - Vascular gene therapy in the 21st century.
AB  - The technology of gene transfer has developed rapidly and has been applied
      successfully as pharmacological therapy in animal models of human vascular
      disease. Human vascular gene therapy has not become a reality although clinical
      trials are starting. In the next century, gene therapy will find its place in the
      vascular physicians' armamentarium as new pharmacological targets are defined and
      new vectors devised for gene transfer. Vascular gene therapy, the use of gene
      transfer to treat diseases of the vascular system, excites the imagination and
      captures the public's attention because it promises at a single step almost
      magically to cure the previously uncurable. The goal has been elusive although
      the promise remains. What can we look forward to in the 21st century? Will the
      dream ever be realized or is it a fantasy that will always be out of reach? The
      sceptics argue that research into pharmacology continues to provide us with
      powerful drugs for the treatment of vascular disease. Why bother with gene
      transfer? Could not the same goals be achieved by more conventional means? These
      questions demand answers and adequate justification. In developing the response,
      we gain a clear understanding of the potential of gene therapy and thereby define
      a better set of objectives. Gene therapy in broad terms covers somatic cell and
      germ line gene therapy. Genetic manipulation of the germ line leads to the
      development of transgenic animals with specific genes that have been deleted or
      overexpressed; these animals are useful for the study of gene function. Their
      organs might also be of use for transplantation into humans. For example,
      transgenic pigs are being developed for this purpose(1). Although the study of
      transgenic animals and the field of germ line gene therapy are of great
      importance for vascular biology, they will not be covered here. This review will
      address vascular somatic gene therapy and will attempt to focus on potential
      targets, progress made in the last decade, and the steps needed to achieve
      clinical application.

PMID- 9198225
TI  - Mechanisms initiating platelet thrombus formation.
AB  - The functions of platelets depend on their ability to interest with surface
      exposed at sites of tissue damage and then with one another after activation,
      thus aggregating into thrombi. This complex process, normally beneficial to
      arrest bleeding during hemostasis, may become a cause of catastrophic disease
      when it leads to thrombotic occlusion of atherosclerotic vessels curtailing
      arterial blood flow to vital organs. Fluid dynamic conditions modulate all
      aspects of platelet response to vascular injury. At higher levels of shear
      stress, encountered both in normal vessels during normal hemostasis or in
      pathological conditions of the vasculature during thrombosis, von Willebrand
      factor becomes the essential adhesive protein for both adhesion and aggregation.
      Two platelet membrane receptors, the glycoprotein complexes Ib-IX-V and IIb-IIIa
      (integrin alpha IIb beta 3), mediate the von Willebrand factor function in a
      coordinate and synergistic manner, each contributing unique biomechanical
      properties to support thrombus formation. The developing understanding of the
      structure and mechanism of action of the key adhesive domains of von Willebrand
      factor, as well as of their cognate cellular and extracellular binding sites,
      will provide solid pathophysiological foundation for the evaluation of novel anti
      thrombotic strategies.

PMID- 9198226
TI  - Mechanisms of bleeding and thrombosis in myeloproliferative disorders.
AB  - Arterial and venous thromboses and microcirculatory disturbances such as
      erythromelalgia and neurologic and visual symptoms are the thrombotic
      manifestations occurring in Polycythaemia Vera and Essential Thrombocythaemia.
      The increased in vivo thromboxane A2 generation existing in these patients and
      the selective sensitivity of erythromelalgia to aspirin suggest that platelet
      PGG/H synthase products may be involved in transducing the increased thrombotic
      risk. The relationship between Thromboxane A2 production and thrombotic accidents
      will be investigated by the European Collaboration on Low-Dose Aspirin in
      Polycythaemia Vera (ECLAP) which will test the efficacy of low-dose aspirin by a
      randomised clinical trial. The haemorrhagic diathesis of polycythaemic and
      thrombocythaemic subjects is generally mild and spontaneous bleeding usually
      manifests in patients with very high platelet count. Its mechanism may be related
      to quantitative as well as to qualitative platelet changes. Possible mechanisms
      linking the high grade thrombocytosis to bleeding are consumption of von
      Willebrand factor and clot fragility due to a mechanical effect of the high
      platelet count or to inhibition of fibrin polymerization by platelet Glycoprotein
      Ib.

PMID- 9198227
TI  - Therapeutic dilemmas: balancing the risks of bleeding, thrombosis, and leukemic
      transformation in myeloproliferative disorders (MPD).
AB  - With these uncertainties, which patients with ET and PV should receive
      myelosuppressive therapy and accept its possible risks? Remembering the
      generalization from the literature that most patients with ET who are to have a
      catastrophic thrombosis either have it at the time of diagnosis or after
      preceding, less severe thrombotic symptoms, it is acceptable to omit
      myelosuppressive therapy in asymptomatic patients with ET. Young patients with PV
      and no thrombotic manifestations can similarly be managed with phlebotomy alone.
      There is no evidence in the literature to show that myelosuppressive therapy
      should be used simply because the platelet count is high or to prevent transition
      to myeloid metaplasia. In patients with ET or PV with previous thrombotic
      manifestations, the risk/benefit ratio probably favors myelosuppressive therapy.
      The PVSG studies also suggest that patients over the age of 70 with PV are at
      particular risk for thrombosis and should be treated with myelosuppression. No
      myelosuppressive agent has been shown to be superior to hydroxyurea. Patients who
      fail on hydroxyurea should not be treated with 32P or alkylating agents.
      Anagrelide or interferon would be more appropriate. The PVSG-05 study suggests
      that high doses of aspirin, i.e. approximately 1.0 grams per day, are not
      indicated. Trials of low dose aspirin to prevent thrombosis are encouraged. There
      is no way to predict which patients will have hemorrhagic complications and, as
      mentioned, one study suggests that there will be few (44). Patients with
      thrombocytosis and pathological bleeding, i.e. hemorrhagic thrombocythemia,
      generally improve with myelosuppressive therapy. This syndrome is to be
      distinguished from patients who bleed with normal or low platelet counts,
      generally in the setting of myeloid metaplasia (14). These patients have an
      acquired disorder of platelet function due to platelet production from abnormal
      megakaryocytes. An occasional patient will benefit from increasing the platelet
      count by splenectomy.

PMID- 9198228
TI  - Independent prostanoid biosynthetic systems associated with prostaglandin
      endoperoxide synthases-1 and -2.

PMID- 9198229
TI  - The Leiden Thrombophilia Study (LETS).

PMID- 9198230
TI  - The epidemiology of inherited thrombophilia: the VITA Project. Vicenza
      Thrombophilia and Atherosclerosis Project.

PMID- 9198231
TI  - Factor VIII inhibitors.

PMID- 9198232
TI  - Analysis of factor VIII inhibitors using hybrid human/porcine factor VIII.
AB  - Recombinant hybrid human/porcine factor VIII molecules have been used to map a
      major determinant of the epitope recognized by human anti-factor VIII A2 domain
      inhibitory antibodies to a region bounded by human fVIII residues Arg484-Ile508.
      This approach is being used to characterize the C2 domain inhibitor epitope. The
      process of creating hybrid human/porcine factor VIII molecules to map inhibitor
      epitopes produces procoagulantly active fVIII with reduced reactivity with
      clinically significant factor VIII inhibitors. This suggests that it may be
      possible to develop of a hybrid human/porcine factor VIII that is useful in the
      management of hemophilia A and acquired hemophilia.

PMID- 9198233
TI  - The fat mouse: a powerful genetic model to study elevated plasminogen activator
      inhibitor 1 in obesity/NIDDM.
AB  - Plasminogen activator inhibitor-1 is elevated in obesity and may be a risk factor
      for obesity/NIDDM related cardiovascular disease. In spite of this, little is
      known about the tissue and cellular origin of elevated PAI-1 in obesity or of the
      mediators and molecular mechanisms that regulate it. We have begun to
      systematically address these issues using genetically obese (ob/ob, db/db) mice.
      Plasma PAI-1 levels were 5-fold higher in obese mice compared to their lean
      counterparts. Subsequent RT-PCR and in situ hybridization studies suggest that
      the increased plasma PAI-1 originates primarily from the adipocyte in response to
      chronically elevated levels of tumor necrosis factor-alpha (TNF-alpha), insulin,
      and transforming growth factor-beta (TGF-beta). Thus, the signals and mechanisms
      that lead to elevated plasma PAI-1 observed in obesity are complex, and appear to
      involve interactions between multiple mediators and the adipose tissue itself.

PMID- 9198234
TI  - PAI-1, obesity, insulin resistance and risk of cardiovascular events.
AB  - Circulating (PAI-1) levels are elevated in patients with coronary heart disease
      and may play an important role in the development of atherothrombosis. Many
      clinical studies have indicated that the insulin resistance syndrome, which is a
      situation predisposing to diabetes and ischemic heart disease, may be a major
      regulator of PAI-1 expression, especially in determining plasma PAI-1 levels.
      Central obesity is a characteristic of insulin resistance and is a well
      recognized risk factor for coronary heart disease. Recently the production of PAI
      1 by adipose tissue, in particular by tissue from omentum, has been demonstrated
      and could be an important contributor to the elevated plasma PAI-1 levels
      observed in insulin resistant patients. Besides the effect of the metabolic
      status on plasma PAI-1 levels, the role of a genetic control has been emphasized,
      but according to recent results obtained in a family segregation study, its
      participation seems limited. Prospective cohort studies of patients with previous
      myocardial infarction or angina pectoris have underlined the association between
      increased plasma PAI-1 levels and the risk of coronary events, but the predictive
      capacity of PAI-1 disappears after insulin resistance marker adjustments. Taken
      together these results support the notion that PAI-1 can be a link between
      obesity, insulin resistance and cardiovascular disease.

PMID- 9198235
TI  - Fibrin tissue adhesives.
AB  - FTA is a promising adjunct treatment in many fields of surgery, mainly in
      patients with acquired and congenital bleeding disorders or in procedures with
      high risk of postoperative bleeding or leaking of air, blood, fluids. Numerous
      report exist for variety of indications, however, very few are well controlled
      and conclusive. There is controversy and contradicting data that stem from
      variability in FTA formulation the selection and design of the operative
      indication the methodology of application including the application devices and
      the skills of the surgeon. Understanding of all these differences and the
      requirements for the certain indication are important for the successful use of
      FTA. It is important to remember that FTA is a blood product and even with more
      than one viral inactivation techniques there should have a clear indication for
      its use. If no clinically important benefit is proven for a certain indication it
      means that contraindication exists.

PMID- 9198236
TI  - Models to study thrombotic disorders.
AB  - Experimental models of thrombosis and vascular injury are important research
      resources that have enhanced our understanding of this pathophysiological
      process. Animal models provide insights into the prevalence of mechanisms that
      have been outlined in isolated cell and protein studies. The availability of
      transgenic and gene knockout animals will allow to pinpoint the relative
      functional importance of single changes in specific gene products in the
      pathophysiological process. The advances generated in our understanding of
      vascular injury and blood interaction with the vascular wall will facilitate the
      formulation of new strategies for cardiovascular protection an the prevention and
      treatment of thrombosis. The importance of thrombosis is highlighted by its
      dramatic consequences, which are the concern of numerous studies aimed at
      improving both treatment and diagnosis (1-3). Ultimately these studies are based
      on the evolving research on the mechanisms of thrombus formation. Blood factors,
      vessel wall factors, and cell-cell interactions in the context of fluid dynamics
      regulate thrombus formation and should be thoroughly investigated.

PMID- 9198237
TI  - Angiogenesis: a dynamic balance of stimulators and inhibitors.
AB  - Angiogenesis, the formation of new blood vessels from a pre-existing vasculature,
      is tightly regulated in normal adults. Under physiological circumstances,
      angiogenesis occurs in only a few instances; e.g., the female reproductive system
      in response to ovulation or gestation, the normal hair cycle, etc. In these
      examples, growth of new capillaries is tightly controlled by an interplay of
      growth regulatory proteins which act either to stimulate or to inhibit blood
      vessel growth. Normally, the balance between these forces is tipped in favor of
      inhibition and consequently capillary growth is restrained. Under certain
      pathological circumstances, however, local inhibitory controls are unable to
      restrain the increased activity of angiogenic inducers. Thus, in wound healing,
      inflammation and tumors, to name just a few examples, angiogenesis is integral to
      the pathology, engendering the hope that these pathological entities could be
      regulated by pharmacological and/or genetic suppression (or enhancement) of blood
      vessel growth. This hope, in turn, has fostered interest in the molecular
      mechanisms that regulate angiogenesis. In this chapter, we have reviewed the
      current literature regarding some angiogenic stimulators and inhibitors,
      emphasizing vascular permeability factor (VPF, also known as vascular endothelial
      growth factor or VEGF), as a major angiogenic inducer, and thrombospondin (TSP)
      as the best known example of a natural inhibitor of vessel growth.

PMID- 9198238
TI  - Angiogenesis in embryos and ischemic diseases.
AB  - Angiogenic growth factors and their endothelial receptors are thought to function
      as major regulators of blood vessel formation. Vascular endothelial growth factor
      (VEGF) and its receptors, Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2), as well as
      Angiopoietin-1 and its receptor, Tie-2, represent key signal transduction systems
      involved in the regulation of embryonic vascular development. The expression of
      these molecules correlates with phases of blood vessel formation during
      embryogenesis. Inactivation of any of the genes encoding these molecules in mouse
      embryos results in defective vascular development and embryonic lethality around
      mid-gestation. In addition, the VEGF signal transduction system has been
      implicated in the regulation of pathological blood vessel growth during certain
      angiogenesis-dependent diseases that are often associated with tissue ischemia,
      such as proliferative retinopathy or solid tumor growth. This hypothesis is
      substantiated by experiments, in which the inhibition of VEGF signal transduction
      resulted in the the inhibition of neovascularization in these diseases. Thus, the
      VEGF signal transduction system represents a useful target for an anti-angiogenic
      therapy.

PMID- 9198239
TI  - New approaches to prevention of deep vein thrombosis.

PMID- 9198240
TI  - Low molecular weight heparin for the out-of-hospital treatment of venous
      thrombosis: rationale and clinical results.
AB  - LMWH preparations have been proven to be safe and effective in the out-patient
      management of acute DVT. Although LMWHs are more expensive than unfractionated
      heparin, the lack of need for laboratory monitoring of LMWHs and their potential
      for out-patient treatment more than offsets the drug related cost difference and
      results in a net cost savings in favour of LMWH. LMWHs have undergone limited
      investigation for the secondary prevention of venous thromboembolism after an
      initial in-patient course of unfractionated heparin. To data, LMWHs have been
      given in prophylactic doses in these trials. In this setting, the LMWHs are
      associated with a similar risk of bleeding as fixed, intermediate dose
      unfractionated heparin in patients with a high risk of bleeding. In patients with
      no increase in bleeding risk, fixed prophylactic dose LMWH appears to be
      associated with both a lower risk of bleeding than warfarin (target INR of 2.0 to
      3.0) and an increased risk of recurrence, although these findings need to be
      confirmed in larger trials.

PMID- 9198241
TI  - Optimal duration of oral anticoagulant therapy in venous thromboembolism.
AB  - Recent trials with sufficient statistical power have demonstrated that the
      duration of oral anticoagulation in many cases need to be extended well beyond 4
      6 weeks. Since many individual factors, as risk of hemorrhage and of recurrence,
      compliance and cost have to be weighed into a decision, it is difficult to issue
      general recommendations. Several of these factors, especially those influencing
      the risk of recurrent event are reviewed here. The ideal solutions will perhaps
      only be achieved when we have learned how to combine the optimal duration with a
      time-adjusted decrease in oral anticoagulation.

PMID- 9198242
TI  - Consequences of tissue factor pathway inhibitor gene-disruption in mice.

PMID- 9198243
TI  - Thrombomodulin gene disruption and mutation in mice.

PMID- 9198244
TI  - Disorders of hemostasis in childhood: risk factors for venous thromboembolism.
AB  - In both children and neonates with venous thrombosis, one or more predisposing
      risk factors can generally be identified. Underlying prothrombotic medical
      conditions are common in these patients. In addition, a "trigger factor" such as
      a catheter, surgery or trauma is usually present. However genetic and acquired
      coagulation abnormalities are also identified in children with venous thrombosis
      who are appropriately studied. A careful family history and assays for the LA, AT
      III, protein C, protein S and the factor V Leiden mutation should be part of the
      evaluation of infants and children with venous thrombosis.

PMID- 9198245
TI  - Arterial thromboembolic complications in paediatric patients.

PMID- 9198246
TI  - Prophylaxis in children with hemophilia: is it the optimal treatment?

PMID- 9198247
TI  - GPIIb/IIIa antagonists: pathophysiologic and therapeutic insights from studies of
      c7E3 Fab.
AB  - Platelet GPIIb/IIIa receptor antagonists have been shown to be more potent than
      aspirin in inhibiting platelet function in vitro and decreasing thrombotic
      vascular events in animal models in vivo. One of these agents (c7E3 Fab,
      abciximab, ReoPro) significantly decreased the ischemic complications of
      percutaneous coronary interventions when given in conjunction with aspirin and
      heparin to patients at high risk of such complications, and other agents
      (Integrelin and tirofiban) have shown favorable trends. This review focuses on
      what we have learned from studies of patients treated with c7E3 Fab, including
      its pharmacology, its potential mechanism(s) of action, the ability to reverse
      its effects with platelet transfusion, and the risks of hemorrhage,
      thrombocytopenia, reinjection, and performing coronary artery bypass surgery. The
      future of GPIIb/IIIa antagonists therapy is considered, including the potential
      of orally active agents.

PMID- 9198248
TI  - Antithrombotic strategies targeting thrombin activities, thrombin receptors and
      thrombin generation.
AB  - Thrombin mediates acute vascular thrombosis and subsequent vascular lesion
      formation following mechanical denuding injury or spontaneous atherosclerotic
      plaque rupture. In the process of generating thrombin Factor VII/VIIa binds
      avidly with tissue factor (TF) exposed on cellular membranes, and coagulation
      serine proteases are sequentially cleaved via macromolecular catalytic complexes
      on phospholipid surfaces. Thrombin activates platelets, blood leukocytes,
      endothelium and vascular smooth muscle cells (SMCs) by cleaving G protein-coupled
      thrombin receptors (TRs), leading to SMC intimal proliferation and synthesis of
      extracellular matrix in the local formation of stenosing neointimal vascular
      lesions. Therapeutic strategies include inactivation of bound thrombin,
      inhibition of TR activation by thrombin, and interruption of thrombin generation.
      In patients having orthopedic surgery, inactivating bound thrombin with direct
      antithrombins markedly reduces venous thromboembolic events, compared with
      heparin or its derivatives, without significant impairment of hemostasis.
      However, acute coronary syndrome patients are not benefitted when given systemic
      direct antithrombins at safe levels, because interrupting TR-dependent platelet
      thrombosis demands systemic levels of direct antithrombins that concurrently
      compromise hemostatic function. Local drug delivery strategies have yet to be
      explored. In preclinical studies: a) enhancing the formation of endogenous
      activated Protein C (APC) by Protein C-selective thrombin mutants produces
      antithrombotic levels of APC; b) inhibiting thrombin activation of TRs abolishes
      platelet recruitment in arterial thrombogenesis in nonhuman primates, while
      sparing fibrin formation in hemostatic plugs; and c) preventing thrombin
      generation by inhibiting precursor serine protease function interrupts the
      formation of both acute thrombosis and chronic stenotic lesions after denuding
      vascular damage without significant hemostatic compromise. TF antagonists appear
      to have a highly favorable efficacy:safety therapeutic relationship for
      preventing the formation of thrombosis and vascular lesions.

PMID- 9198249
TI  - Thrombolytic therapy.
AB  - Despite their widespread use in patients with acute myocardial infarction, all
      currently available thrombolytic agents suffer from a number of significant
      limitations, including resistance to reperfusion, the occurrence of acute
      coronary reocclusion and bleeding complications. Therefore, the quest for
      thrombolytic agents with a higher thrombolytic potency, specific thrombolytic
      activity and/or a better fibrin-selectivity continues. Several lines of research
      towards improvement of thrombolytic agents are being explored, including the
      construction of mutants and variants of plasminogen activators, chimeric
      plasminogen activators, or plasminogen activators from animal or bacterial
      origin. Several of these new thrombolytic agents have been evaluated in animal
      models of venous or arterial thrombosis, some in pilot studies in patients with
      acute myocardial infarction and a few in large clinical trials with mortality end
      points. Definition of their relative therapeutic benefit, against presently
      available "classical" thrombolytic agents will require further dose-finding
      studies and randomized clinical trials.

PMID- 9198250
TI  - Regulation of the tissue factor gene.
AB  - Tissue factor is a cellular receptor that initiates blood coagulation. The TF
      gene is constitutively expressed in some extravascular cell types and is
      inducibly expressed in several vascular cell types, including monocytes, vascular
      endothelial cells and vascular smooth muscle cells. Functional studies indicate
      that Sp1 controls basal TF gene expression. A distal enhancer (-227 to -172)
      containing two AP-1 sites and an NF-kappa B site mediates induction of the human
      TF promoter in monocytic cells and endothelial cells. Similarly, two AP-1 sites (
      220 to -200) regulate induction of the murine TF promoter in fibroblast-like
      cells. In contrast, proximal enhancers in the human TF (-109 to -59) and rat (
      103 to -80) TF promoters containing Egr-1 and Sp1 sites mediate induction in
      epithelial-like cells and vascular smooth muscle cells, respectively. These
      results suggest that cell type-specific pathways regulate TF gene expression.

PMID- 9198251
TI  - Tissue factor: a complex biological role.

PMID- 9198252
TI  - Tissue factor in health and disease.
AB  - Over the last years numerous studies have focussed on the in vivo expression of
      tissue factor (TF) in health and disease. The selective perivascular distribution
      of TF and the lethal effects of TF knockouts have added strong support to the
      widely accepted view that TF plays a pivotal role in the initiation of blood
      coagulation during physiological hemostasis. Inappropriate in vivo expression of
      TF, particularly by cells that do not express this protein under normal
      conditions (mainly monocyte-macrophages and endothelial cells), has been
      documented and is likely responsible for fibrin deposition in a variety of
      pathological conditions, among which sepsis-associated disseminated intravascular
      coagulation (DIC) and thromboembolic disease. In malignancy, in vivo expression
      of TF by tumor cells and/or by host cells has been implicated not only in
      intratumoral and systemic activation of blood coagulation but also in tumor
      growth and dissemination.

PMID- 9198253
TI  - Hormone replacement therapy and haemostatic function.

PMID- 9198254
TI  - Postmenopausal hormone replacement therapy and cardiovascular disease.
AB  - Cardiovascular disease is the leading cause of mortality in postmenopausal women
      in developed countries. A possible cardioprotective role of hormone replacement
      therapy (HRT) is suggested by epidemiologic studies of HRT and reduced risk of
      coronary heart disease, as well as by randomized trials of HRT and lipid
      subfractions. Estrogen has beneficial effects on the lipid profile, raising high
      density lipoprotein cholesterol levels and reducing low-density lipoprotein
      cholesterol levels each by approximately 10%. Other possible biologic mechanisms
      include beneficial effects on vascular function, oxidative status, endothelial
      dependent vasodilation, intimal hyperplasia and insulin sensitivity. Estrogen's
      net effects on coagulation and fibrinolysis are less clear. Estrogen replacement
      therapy is associated with decreased atherosclerosis in several animal models.
      However, most of the available data on HRT derive from observational studies or
      small randomized trials assessing biologic intermediates rather than clinical
      events. Further research, including large-scale randomized clinical trials, are
      required to evaluate definitively the role of estrogen replacement therapy,
      especially given uncertainties about the effects of combined estrogen-progestin
      therapy and the balance of benefits and risk of this common intervention in
      postmenopausal women.

PMID- 9198255
TI  - Gait analysis, isokinetic muscle strength measurement in patients with
      Parkinson's disease.
AB  - The aim of this study was to describe motor performance in Parkinson patients in
      relation to controls. Gait, concentric isometric and eccentric strength in the
      ankle dorsiflexors were investigated in 25 patients with Parkinson's disease and
      in 37 control subjects of the same age. In patients concentric torque was
      significantly lowered but, eccentric torque was significantly lowered in male
      patients only. Among controls a significant difference in strength was found
      between sexes. This was not found in the patient group. No correlation between
      strength tests and clinical ratings was found in the patient group. Patients
      walked with significantly lower maximum and ordinary velocity, compared with
      controls. At constant velocity, stride length was shorter, single support had a
      shorter duration. The duration for heel on to ball on in males was shorter,
      reflecting the flat foot strike of Parkinson patients. Single support and the
      duration of heel on to ball on correlated significantly to the clinical ratings
      in male but not in female patients. In the male group of patients there was a
      relation between concentric strength on the one hand and gait velocity, stride
      length and stride frequency on the other. Female patients generally had fewer
      symptoms and less deviation from their respective controls in the measurements.
      The comparatively simple neurophysiological tests presented here may be suitable
      for evaluation of patients with Parkinson's disease.

PMID- 9198256
TI  - Double-limb support and step-length asymmetry in below-knee amputees.
AB  - The sequence of gait events and symmetry of kinematic parameters between both
      lower limbs are compromised in below-knee amputees. In the present study the
      periods of double-limb support and the step length in below-knee amputees were
      investigated. The symmetry of the two periods of double-limb support occurring in
      each stride was obviously abnormal (ratio: 0.74) among temporal and distance
      parameters. The time of double-limb support (0.211 +/- 0.05 seconds) measured
      from heel-strike of the amputated leg until toe-off of the normal leg was
      significantly longer (p = 0.011) when compared with the contralateral leg (0.173
      +/- 0.04 seconds). The step length of the normal leg (0.709 +/- 0.07 m) was
      significantly (p = 0.045) shorter than that of the amputated leg (0.752 +/- 0.08
      m). Most of these differences between measured kinematic parameters can be
      explained by the limited ability of the prosthesis ankle-foot component to
      reproduce the normal functions of both foot and ankle.

PMID- 9198257
TI  - Comparison of three intensive programs for chronic low back pain patients: a
      prospective, randomized, observer-blinded study with one-year follow-up.
AB  - In a randomized, blinded study, we compared the outcome from a full-time
      functional restoration program with the outcome from shorter active
      rehabilitation programs for patients with chronic, disabling low back pain. The
      study initially included 132 patients, randomized into one of three treatment
      programs: (1) an intensive 3-week multidisciplinary program; (2) active physical
      training and back school; or (3) psychological pain management and active
      physical training. Nine of the randomized patients never started in any program,
      so the studied population consisted of 123 patients. Of these, 14 patients (11%)
      dropped out. The results presented here are at 1 year following treatment, where
      we achieved a 92% response rate, including the drop-outs. The functional
      restoration program was superior to the shorter programs as to work-ready rate,
      health care contacts, back pain level, disability level, staying physically
      active, and reduction in analgesics. There was no significant difference between
      Programs 2 and 3 in most of these parameters. As for sick leave and leg pain,
      there was no significant difference between Programs 1 and 2, although a
      difference was observed when comparing Program 3 with each of the other two.
      Conclusively, it seems that there is human, as well as economical, benefit from a
      functional restoration program compared to less intensive programs for these
      patients.

PMID- 9198258
TI  - Comorbidity of personality disorders and major depression in patients with
      somatoform pain disorders or medical illnesses with long-standing work
      disability.
AB  - The comorbidity between major depression and personality disorders in patients
      with long-standing work disability at a rehabilitation clinic was investigated.
      Sixty patients with a somatoform pain disorder and 66 patients with different
      medical illnesses were assessed by means of a self rating scale for major
      depression, and the SCID screen personality disorder questionnaire. In the total
      series, 27% of the patients had a diagnosis of major depression and 34.9% had at
      least one personality disorder. Personality disorders were significantly more
      common in patients with medical illness than in patients with a somatoform pain
      disorder. There was a high frequency of comorbidity between major depression and
      personality disorders, especially borderline and avoidant personality disorders.
      If this is due to a common pathogenetic mechanism, it could explain why SSRIs are
      effective in both depression and some personality disorders.

PMID- 9198259
TI  - Muscle strength, working capacity and effort in patients with fibromyalgia.
AB  - The objective of the study was to evaluate the physical capacity and effort in
      patients with fibromyalgia. Muscle strength and the coefficient of variation of
      the strength measurements of 181 female fibromyalgia patients and 126 healthy
      females were compared. These measurements and ergometer exercise capacity, work
      status and psychometric scoring (SCL-90-R) were correlated. The fibromyalgia
      patients exhibited significant reduction in voluntary muscle strength of the knee
      and elbow, flexors and extensors in the order of 20-30%. However, the coefficient
      of variation was higher among patients, thus indicating lower effort. The
      physical performance during an ergometer test corresponded to a maximal oxygen
      consumption of 21 ml/kg-1 x min-1. The maximal increase in heart rate was only
      63% (44-90%) of the predicted increase. Degree of effort or physical capacity did
      not correlate to psychometric scores. Work status was related to psychometric
      scoring, but not to physical capacity or effort. In conclusion, we found a low
      degree of effort but near normal physical capacity in the fibromyalgia patients.

PMID- 9198260
TI  - A randomized prospective study of vocational outcome in rehabilitation of
      patients with non-specific musculoskeletal pain: a multidisciplinary approach to
      patients identified after 90 days of sick-leave.
AB  - This study was designed to evaluate the effectiveness of a multidisciplinary
      rehabilitation programme offered to a general population with 90 days of sick
      leave due to non-specific musculoskeletal pain. The results concerning return to
      work and re-sick-listing during a follow-up period of five years were evaluated
      for Swedes and immigrants separately. Compared to a control group, the
      rehabilitation offer resulted in improved work stability after work return among
      the Swedes. The immigrants, as a group, did not benefit from the programme
      compared to the controls in primary care.

PMID- 9198261
TI  - Factors influencing vocational outcomes following stroke in Taiwan: a medical
      centre-based study.
AB  - This study was aimed at identifying the factors relating to return to work for
      stroke patients of working age in Taiwan, adjusting for confounding factors. A
      retrospective cohort study was used to test the association between patients'
      characteristics, such as medical condition at admission and sociodemographic
      factors, and the degree of return to work after stroke. Two hundred and forty
      eight consecutive stroke survivors discharged from the National Taiwan University
      Hospital participated in the follow-up survey. Variables considered likely to
      influence return to work were collected from the patients' hospital records.
      Vocational outcomes were collected via questionnaire. Return to work was
      classified into four levels: (I) no return to work; (II) limited return to work;
      (III) partial return to work; and (IV) complete return to work. Of the 248
      subjects surveyed, 105 (42.7%) subjects had not returned to work, 32 (12.9%)
      subjects had returned to work on a limited basis, 43 (17.3%) subjects had
      partially returned, and 68 (27.4%) subjects had returned to work completely.
      Cramer's V test and stepwise logistic regression were employed to examine factors
      influencing return to employment. Maximum weakness and employment institution
      were identified as the strongest predictors of return to work. In brief, nearly
      three-quarters of the patients did not resume their usual work roles after
      stroke. Maximum weakness and employment institution were the strongest predictors
      of return to work following a stroke in Taiwan.

PMID- 9198262
TI  - Peripheral muscle training in patients with clinical signs of heart failure.
AB  - The aim of the study was to evaluate, in a controlled setting, the effects of a 5
      month dynamic peripheral training programme in patients with clinical signs of
      congestive heart failure with special reference to their anaerobic threshold,
      muscle function, heart rate variability and quality of life. Twenty-four
      randomized patients with clinical signs of heart failure in NYHA II-III entered
      the study. Training resulted in a significant (p = 0.01) change in the anaerobic
      threshold, the patients' ability to lift weights (p = 0.01) and performance of
      heel-lift (p = 0.01). The heart rate recorded during the training exercises
      decreased significantly (p = 0.04). There were no significant differences in peak
      oxygen uptake, isokinetic and isometric strength, HRV and quality of life except
      for three items in the control group. The results of this study indicate that
      peripheral training is beneficial for patients with clinical signs of congestive
      heart failure.

PMID- 9198263
TI  - [A test of a hypothesis of automatic phonological processing of Kanji words].
AB  - This paper aims to examine a hypothesis that phonological processing should occur
      in Japanese Kanji words as well as in Kana words, but automatic in Kanji words.
      In Experiment 1, subjects performed concurrent articulation or finger tapping
      during a semantic processing task of Kana words with 2 to 4 phonemes, for which
      phonological processing should be indispensable. Concurrent articulation was
      found to eliminate the phoneme number effect found in the control condition, but
      finger tapping was not. This result indicates the effectiveness of concurrent
      articulation in articulatory suppression. In Experiment 2, the materials were
      changed to Kanji words, for which phonological processing had been supposed to be
      dispensable, and subjects performed the same task. The results showed no phoneme
      number effect even in the control condition, and the reaction time in the
      concurrent articulation condition was delayed significantly. These results
      suggest the existence of automatic phonological processing of Kanji words.
      Finally, the pertinence of this hypothesis was confirmed by applying it to the
      explanations of 3 kinds of Japanese dyslexia.

PMID- 9198264
TI  - [Characteristics of multimedia counseling: a study of an interactive TV system].
AB  - The purpose of this study was to investigate communication characteristics of
      multimedia counseling. Eye-contact through an interactive TV system was made
      possible, within three degrees of angle, with a camera attached on the TV
      screens. Counseling sessions with 18 clients were conducted to study differences
      among three conditions: audio only, interactive TV, and conventional face-to
      face. The variables examined were information transmission, feeling
      communication, rapport building, overall evaluation, etc. Eighty-three per cent
      of the clients positively evaluated the interactive TV system, with all of its
      indices significantly higher than the audio only condition. However, rapport
      building with the system was significantly lower than the face-to-face condition.
      Two common factors found for the conditions were defenseless communication and
      counselor warmth. A larger TV screen might facilitate rapport building. More work
      is needed to study applicability of multimedia counseling, as well as to develop
      new effective counselor styles for the kind of counseling.

PMID- 9198265
TI  - [Self-evaluation on the ability to retrieve Kanji words: a comparison between an
      aphasiac and normal subjects].
AB  - The present study investigated the accuracy of an aphasiac's self-evaluation on
      his ability to retrieve words. The aphasiac and six normal subjects were shown a
      list of words and that of drawings. The words were written in Kanji and the
      drawings could be translated into the Kanji words. For each word, the subjects
      rated the likelihood that they could write it, and for each drawing, they rated
      the likelihood that they could translate it into the Kanji word. A week later,
      they were asked to translate drawings into Kanji words, and the performance and
      self-ratings were compared. Although the aphasiac could write far less Kanji
      words than the normals, his self-rating was as high as the normals. It was
      suggested that metamnemonic judgments are based on the indirect inferential
      processes, not on the direct access to the memory-traces. In other words, the
      aphasiac might raise his rating scores when Kanji words or drawings seemed easy
      to understand.

PMID- 9198266
TI  - [Mood-congruency effects in self-relevant words].
AB  - In this experiment, one of three moods: positive, negative, neutral, was induced
      with Velten technique and music. Subjects were then presented with a word at a
      time from a list of trait words, which were pleasant, unpleasant, or neutral.
      They were to decide whether the word described their self, and respond with 'yes'
      (relevant) or 'no' (irrelevant) buttons. After the task, they were given five
      minutes for an incidental free recall test. Results indicated that induced mood
      affected memory, but not judgements of self-relevance. Mood congruent recall
      effects were found only for self-relevant words, and more self-relevant than
      irrelevant words were recalled if they were mood congruent. It was concluded that
      mood effects were different depending on whether the information was self
      relevant, and that mood-congruency effects were found only for self-relevant
      information.

PMID- 9198267
TI  - [The effects on image instructions and spontaneous use of imagery on the self
      control of skin temperature].
AB  - The aim of this study was to examine the effects of image instructions on
      subjects able to use imagery spontaneously and those unable to use them
      spontaneously, on the self-control of skin temperature. The subjects were 20
      undergraduate students. All subjects were instructed to raise their skin
      temperatures through four sessions. After the first session, subjects were
      assigned to one of the following three groups: the spontaneous image group (SI),
      instructed image group (II), and control group (C). The SI group comprised only
      of those subjects who used imagery spontaneously in the first session. Before the
      second session, the subjects in the SI and II groups were instructed to use
      imagery in the following sessions. The results showed that SI group subjects
      could raise their skin temperatures to higher levels than those in the other
      groups. These results suggest that subjects who use imagery spontaneously have a
      greater ability to control their skin temperatures, than other subjects who
      cannot raise their skin temperatures well, even if instructed in the use of
      imagery.

PMID- 9198268
TI  - [The effects of a fimbria-fornix lesion on distance discrimination in rats].
AB  - In order to study the role of hippocampus in spatial learning, fimbria-fornix
      (FF) lesioned and control rats, eight each, were trained for a distance
      discrimination task in a rectangular test box (120 x 60 x 35 cm). A rat was
      placed in a start box at one of the corners of the test box, and then released to
      choose the bottle that contained food reward. Two bottles, at the distance of 50
      cm, were placed along the walls, one short and the other long, on either side of
      the start box, and to find the reward the rat had to discriminate the distance,
      i.e., short vs. long wall of the test box. Results showed that control rats were
      able to make the discrimination, while FF rats were not. The finding suggests
      that hippocampus plays an important role in processing distance information in
      general, and distance discrimination in particular.

PMID- 9198269
TI  - [A choice of domain of judgment in acquisition of universal quantifier
      expressions].
AB  - The present paper examined whether 3-5 year old children can answer correctly to
      universal quantifier expressions which refer to elements in front of them. In
      Experiment 1, likely and unlikely situations, manipulated by entity color
      relation (e.g., likely: red flower, unlikely: black moon), were presented. The
      result showed that a large number of 4-5 year old children could not affirm the
      true but unlikely situations. In Experiment 2, the elements which did not have
      any typical color were used in the likely situations. Children made incorrect
      judgment equally to both likely and unlikely situations. However, in Experiment
      3, those children were able to affirm or negate situations in front of them
      correctly, if the elements were novel to them. These results indicate that in
      true-false judgment for universal quantifier expressions, 4-5 year old children
      tend to base their judgment on their knowledge rather than situations just in
      front of them. This phenomenon is discussed from the point of view of
      intellectual realism.

PMID- 9198270
TI  - [Review of the research on "theory of mind"].
AB  - The concept "theory of mind", first proposed by Premack and Woodruff (1978), has
      drastically changed our view of the mind. In the first half of this paper, the
      concept's history and recent developments were reviewed. Included were studies of
      non-human primates, normal children, and autistic children, in addition to some
      philosophical discussions. The "false belief" paradigm has been successful in
      understanding children older than 4 years and in characterizing children with
      high-functioning autism. But with the paradigm alone, it is difficult to explain
      the "mind" of most non-human primates, younger children, and a large part of
      autistic children. In the second half, a theoretical discussion was made to
      understand early developments of mind. The theory theory and competing theories
      of modularity, simulation, and intersubjectivity were compared concerning the
      observability of mind (of self and others), the basic mechanisms for
      understanding the mind, the indispensability of theorizing the mind, and the need
      for metarepresentation in pretend plays.

PMID- 9198271
TI  - Relationship between the time courses of power in the frequency bands of human
      sleep EEG.
AB  - The time course of the different frequency bands in the human sleep EEG spectrum
      within separate NREM and REM episodes averaged over 24 healthy subjects is
      measured and plotted with the aim of studying their inter-relationship and also
      the particularities of the beta band. In NREM, a negative sigma-delta cross
      correlation corresponding to that expected from neurophysiological data, is found
      only in the central zone of each episode. The overall correlation is found to be
      negligible. A neurophysiological explanation is proposed to account for some
      aspects of this sigma-delta relation. Below the beta frequency range in NREM, the
      sequence of build-up in power for the different frequencies is from fast to slow,
      suggesting that there may be a smooth progression in the frequency of oscillation
      of the thalamocortical neurons depending on their degree of polarization. The
      beta band is the only one showing a reciprocal relationship with delta throughout
      the NREM episode, and it is the only one not declining in the REM episode. These
      differences, together with the close similarity of the beta evolution with that
      of the REM-on neuronal activity, suggest that beta could directly reflect this
      activity.

PMID- 9198272
TI  - '1996' starting the modern era of biologics regulation: FDA's elimination of
      establishment licensure and other changes.
AB  - On May 14, 1996, the U.S. Food and Drug Administration (FDA) issued a new
      regulation eliminating the establishment licensure requirement for certain
      'specified' biologics and expanded the definition of 'manufacturer' for biologic
      products in general. These regulatory changes are a significant change in the
      history of biologics regulation and are the logical culmination to the FDA's
      recent efforts to make modern biologics regulation conform to modern biologics
      technology. This regulation essentially placed modern biologics on an equal
      regulatory and commercial footing with traditional chemical drug products.
      Executives, legal counsel of biologics manufacturers, and researchers developing
      biologics need to review their regulatory strategies and commercial agreements in
      light of these extraordinary changes.

PMID- 9198273
TI  - Artificial-capillary-system development of human alloreactive cytotoxic T
      lymphocytes that lyse brain tumours.
AB  - The production of alloreactive cytotoxic T-lymphocytes (CTL) for therapy of
      recurrent brain tumours was performed in the CELLMAX artificial capillary system
      composed of cell-culture modules containing cellulose acetate or cuprammonium
      rayon hollow fibres. Lymphocytes, obtained from the brain-tumour patient to be
      used for sensitization, were stimulated with OKT3 (anti-CD3) and interleukin-2
      (IL-2) and inoculated into the extracapillary space of artificial capillary
      modules. For allogeneic CTL production, the expanded patient lymphocytes were
      harvested, irradiated and placed into a second artificial capillary system with
      allogeneic lymphocytes from a healthy donor. In a one-way mixed lymphocyte
      reaction, CTL developed in the presence of low-concentration IL-2 (60 i.u. of IL
      2/ml). In 18-21 days the cell preparation usually displayed a predominantly CD3+,
      CD8+ phenotype, which consorted with the dual-labelled CD8/CD11a markers used to
      identify CTL. Chromium (Cr)-release assays demonstrated lysis of patient tumour
      in relation to allogeneic glioma; the response observed in cold-target-inhibition
      assays confirmed lysis of the relevant tumour by the CTL.

PMID- 9198275
TI  - Parameters influencing the expression of mature glial-cell-line-derived
      neurotrophic factor in Escherichia coli.
AB  - Factors governing expression in Escherichia coli, namely promoters, fusion
      partners, targeting signals, host strains, growth temperature of cultures and
      inducer concentrations, were investigated to elucidate their influence on the
      accumulation of mature glial-cell line-derived neurotrophic factor (GDNF). The
      present study provided evidence indicating that translational and/or post
      translational events were more important in determining overall accumulation of
      the target protein than was transcription. Under the control of the strong
      inducible tac or T7 promoter, no direct correlation between transcript abundance
      and final yield of recombinant protein was observed. GDNF was also recalcitrant
      to being produced in a soluble form in E. coli. Direct expression resulted in the
      exclusive localization of GDNF in inclusion bodies, regardless of whether the
      protein was produced in the cytoplasm or targeted to the periplasm. The fusion
      approach was found to be the most efficient method, as it resulted not only in
      the highest level of GDNF produced, albeit primarily in inclusion bodies, but
      also in the accumulation of small amounts of soluble proteins. Using different
      host strains, low inducer concentration or sub-optimal growth temperature did not
      result in any detectable shift towards solubility. Persistent localization in
      inclusion bodies, low levels of expression as a native protein and in vivo
      proteolysis of soluble fusion forms appeared to be influenced by structural
      features located at the N-terminus of GDNF. Deletion of this region was found to
      result in substantial alleviation of these problems.

PMID- 9198274
TI  - Use of pEX and pGEX bacterial heterologous protein expression systems for
      recombinant oncoprotein production and antisera generation.
AB  - In order to study the role played by known and novel genes in growth control and
      neoplasia, we here compare the pEX and pGEX bacterial expression systems for
      recombinant oncoprotein production and for generation of specific antisera. The
      results of five pEX (MS2-c-Fos, MS2-Fra-1, MS2-JunD, bgal-c-Jun and bgal-JunB)
      and two pGEX [glutathione S-transferase (GSH)-JE/MCP-1 and GST-JunD] fusion
      protein productions are presented. Higher (15-43-fold) yields are obtained with
      the pEX system, but only the pGEX system allows separation of the protein of
      interest from the fusion moiety by digestion with specific proteases. The degree
      of fusion-protein purification, as assessed by SDS/PAGE, is similar for both
      systems. Proteins produced by both systems were successfully used in the
      generation of specific antisera. The choice between the pEX and pGEX systems is
      dependent upon the specific recombinant protein produced.

PMID- 9198276
TI  - Sources and nature of heterogeneity in recombinant phenol hydroxylase derived
      from the basidiomycetous soil yeast Trichosporon cutaneum.
AB  - Preparations of the dimeric flavoenzyme phenol hydroxylase derived from
      Trichosporon cutaneum were found to contain an active tetrameric form when the
      enzyme was produced in Escherichia coli. The relative content of the tetramer was
      estimated from scans of silver-stained native PAGE gels and/or size-exclusion
      chromatography (SEC). Proportions of up to 22% of the enzyme protein, depending
      on the growth temperature and the level of added inducer, were observed in
      independent cultures as well as in purified preparations. No tetramer was ever
      seen in cell extracts or purified preparations from T. cutaneum. Traces of higher
      multimers and of possibly deamidated species were also detected in preparations
      of the recombinant enzyme. The rate of enzyme production seems to be the major
      factor in promoting formation of the tetramer, whereas the specific growth rate
      of the fermentor culture appears to be of minor importance. The dimeric and the
      tetrameric forms were purified using either SEC or ion-exchange chromatography as
      a final step. The two purified species did not interchange under a variety of
      conditions, indicating that they are not undergoing rapid equilibria. The FAD of
      either form, as isolated by SEC, was present to a lower-than-expected extent of 2
      equiv/dimer. However, by removing FAD and reconstituting the resulting
      apoproteins with the cofactor, the FAD content could be increased to 2 equiv. in
      the dimer and 3 equiv. in the tetramer. Both reconstituted forms exhibited
      absorption spectra identical with that of phenol hydroxylase from T. cutaneum as
      well as that of the recombinant enzyme. All spectra were equally perturbed by one
      equivalent of phenol per enzyme-attached FAD. The ratio of specific activities of
      the dimeric and the tetrameric forms was, however, lower than expected from the
      ratio of their FAD contents. The results are compatible with the notion that the
      tetramer consists of a native phenol hydroxylase dimer associated with a non
      native one with a decreased ability to bind FAD, either in one or both of its
      constituent 'monomers'.

PMID- 9198277
TI  - Gene replacement in Staphylococcus carnosus and Staphylococcus xylosus.
AB  - A system for high-efficiency gene replacement in Staphylococcus carnosus and
      Staphylococcus xylosus has been developed, that is based on temperature-sensitive
      Escherichia coli-Staphylococcus shuttle vectors for fragment delivery and
      erythromycin resistance cassettes to facilitate selection of genomic copies of
      disrupted genes. The approach was tested by constructing a phosphotransferase
      deficient mutant of S. carnosus and an S. xylosus mutant strain unable to utilize
      sucrose. Allelic replacements were observed at rather high frequencies, ranging
      from approximately 10% for the ptsI gene in S. carnosus up to 50% for the scrB
      gene in S. xylosus. These differences most likely reflect the length of homology
      rather than strain-specific variations in recombination efficiencies. Apart from
      the staphylococcal species tested in this study, the system appears to be
      applicable in other staphylococci.

PMID- 9198278
TI  - Identification of the pac promoter from Kluyvera citrophila.
AB  - The nucleotide sequence of the 5'-terminal region of the pac gene encoding the
      penicillin G acylase from Kluyvera citrophila ATCC 21285 has been determined. The
      transcriptional start site has been identified by primer extension analysis in a
      different position to that previously found for the homologous pac gene of
      Escherichia coli W ATCC 11105. Two nucleotide changes in the -35 box appear to be
      responsible of the promoter displacement in K. citrophila. A putative upstream
      promoter element (A+T-rich enhancer sequence) and a binding site for the cAMP
      receptor protein (CRP) were located upstream of the -35 box. Transcriptional lacZ
      and cat fusions demonstrated that pac expression was subjected to catabolite
      repression mediated by cAMP and its receptor protein. Remarkably, phenylacetic
      acid which is a potent inducer of the penicillin G acylase from E. coli, was only
      able to cause a significant induction of the pac expression in CRP+ cells
      cultured in the presence of glucose, suggesting that this effect is CRP
      dependent.

PMID- 9198279
TI  - Suppression of heterocyst differentiation in Anabaena PCC 7120 by a cosmid
      carrying wild-type genes encoding enzymes for fatty acid synthesis.
AB  - A cosmid containing a wild-type Anabaena PCC 7120 DNA fragment was found to
      suppress heterocyst differentiation, creating a Het phenotype in an otherwise
      wild-type strain. Curing of the cosmid restored the full wild-type Het+ Nif+
      phenotype. The cosmid contains at least four genes encoding proteins with
      significant sequence similarity to enzymes involved in the synthesis of fatty
      acids. Selection for Nif+ revertants of the suppressed strain yielded modified
      cosmids, one of which contained a 10.2-kb transposon, Tas1, inserted into the
      promoter region of a gene encoding a protein with acyl carrier and beta-keto
      reductase domains. This gene, called hetN, was shown previously by Black and Wolk
      (J. Bacteriol. (1994) 176, 2282-2292) to inhibit heterocyst differentiation when
      present alone on a plasmid. Oddly, hetN gene transcription is detected later than
      6 h into heterocyst differentiation.

PMID- 9198280
TI  - Cloning and characterization of the Neisseria meningitidis rfaC gene encoding
      alpha-1,5 heptosyltransferase I.
AB  - We cloned and characterized the Neisseria meningitidis rfaC gene which encodes an
      enzyme, alpha-1,5 heptosyltransferase I, involved in the synthesis of the deep
      core of the lipooligosaccharide. The N. meningitidis rfaC mutant, obtained by an
      allelic exchange, produced lipooligosaccharide which migrated faster in sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis than the lipooligosaccharide
      isolated from the wild-type N. meningitidis. The N. meningitidis rfaC mutant was
      not affected by growth in a rich microbiological medium and did not show any
      defect in adhesion to epithelial cell lines. Conversely, the rfaC mutant was
      attenuated in the infant rat model of meningococcemia, thus confirming the
      importance of intact lipooligosaccharide in the virulence of N. meningitidis.

PMID- 9198281
TI  - Glycolytic enzyme activities in Cryptosporidium parvum oocysts.
AB  - Oocysts of Cryptosporidium parvum were obtained from an experimentally infected
      newborn goat. After purification, the oocysts were homogenised and the activities
      of the glycolytic enzymes measured in the different subcellular fractions. All of
      the activities of the Embden-Meyerhoff pathway were located in the non
      sedimentable, cytoplasmic fraction. Under the conditions used, hexokinase
      activity was below the limits of detection. The pathway is also characterised by
      the presence of a pyrophosphate-dependent phosphofructokinase and a carbon
      dioxide-fixing cycle comprising phosphoenolpyruvate carboxylase, malate
      dehydrogenase and malate dehydrogenase (decarboxylating) activities. The data
      presented in this paper suggest that the infective stage of this parasite
      probably relies on substrate-level phosphorylation for energy generation.

PMID- 9198282
TI  - Identification of an elastolytic protease in stationary phase culture filtrates
      of M. tuberculosis.
AB  - Culture filtrate from M. tuberculosis grown in Sauton broth was screened at
      weekly intervals for elastase and caseinase activity. Both activities were
      detected concomitantly at 4 weeks and had similar inhibitor and pH profiles.
      Highest activity occurred between pH 6.5 and pH 7.5. Azocaseinase activity was
      linear with time between 12 and 28 h at 37 degrees C. Enzymatic activity was
      inhibited by EDTA, EGTA, dithiothreitol, ethylmaleimide, 1,10-phenanthroline,
      Zincov, N-tosyl-L-phenylalanine chloromethyl ketone, and N-methoxysuccinyl-Ala
      Ala-Pro-Val chloromethyl ketone. SDS-PAGE analysis revealed breakdown of casein
      after incubation with culture filtrate. These results indicate the presence of a
      calcium-dependent, elastolytic metalloprotease in stationary phase cultures of M.
      tuberculosis.

PMID- 9198284
TI  - Effects of carbonylcyanide-m-chlorophenylhydrazone (CCCP) and acetate on
      Escherichia coli O157:H7 and K-12: uncoupling versus anion accumulation.
AB  - Non-growing cells of Escherichia coli O157:H7 and K-12 that were incubated
      anaerobically in sodium phosphate buffer at pH 6.5 consumed glucose at a rate of
      approximately 8 mumol.(mg protein)-1.h-1 and had intracellular pH values of 7.3
      and 7.5, respectively. The uncoupler, carbonylcyanide-m-chlorophenylhydrazone
      (CCCP), caused a marked decrease in intracellular pH, ATP and potassium of both
      strains. Low concentrations of CCCP stimulated glucose consumption rate, but
      higher concentrations were inhibitory. Acetate also caused a decrease in
      intracellular pH, but it never caused a large decrease in glucose consumption
      rate. Acetate decreased the intracellular ATP of E. coli K-12, but it had no
      effect on the ATP of O157:H7. Acetate had no effect on the intracellular
      potassium of E. coli O157:H7, and acetate-treated K-12 cells had even more
      potassium than untreated controls. Based on these results, acetate and CCCP
      appear to have different effects on E. coli. The comparison of E. coli O157:H7
      and K-12 indicated that intracellular pH, acetate accumulation and intracellular
      potassium were related. E. coli K-12 maintained a higher intracellular pH than
      O157:H7, accumulated more acetate and had a greater intracellular potassium.

PMID- 9198283
TI  - M protein mediated adhesion of M type 24 Streptococcus pyogenes stimulates
      release of interleukin-6 by HEp-2 tissue culture cells.
AB  - We investigated the contributions of lipoteichoic acid and M protein to
      reversible and irreversible adhesion of group A streptococci and the effects of
      such adhesion on release of interleukin-6. Streptococci in which lipoteichoic
      acid was masked by the hyaluronate capsule were readily washed from HEp-2 cells,
      indicating no attachment. Unencapsulated, M-negative streptococci in which
      lipoteichoic acid was exposed were removed more slowly, indicating loose
      attachment. Only unencapsulated streptococci that expressed both lipoteichoic
      acid and M protein remained stably adherent to HEp-2 cells throughout multiple
      washes. Streptococci expressing both M protein and lipoteichoic acid induced
      release of interleukin-6 from HEp-2 cells, whereas an isogenic, M-negative mutant
      failed to induce release of interleukin-6. These data suggest that lipoteichoic
      acid mediates reversible adhesion and that M protein is required for irreversible
      adhesion and for inducing release of interleukin-6 from HEp-2 cells.

PMID- 9198285
TI  - Interaction between Actinobacillus actinomycetemcomitans lipopolysaccharides and
      human hemoglobin.
AB  - Actinobacillus actinomycetemcomitans, a bacterium associated with juvenile
      periodontitis, was found to use human hemoglobin as a source of iron for cell
      growth. Cultivation in the presence of hemoglobin had only a slight effect on the
      cellular protein pattern, as determined by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis analysis. Lipopolysaccharides obtained from A.
      actinomycetemcomitans were found to have a strong capacity to bind hemoglobin.
      This interaction appears not to involve the lipid A portion of the molecule as no
      inhibition was obtained when lipopolysaccharides were pre-treated with polymyxin
      B. This interaction between hemoglobin and lipopolysaccharides of A.
      actinomycetemcomitans may facilitate iron acquisition by this bacterium.

PMID- 9198286
TI  - Degradation of the cyanobacterial hepatotoxin, nodularin, under light and dark
      conditions.
AB  - The stability of the cyanobacterial hepatotoxin, nodularin, was determined during
      the incubation of purified toxin, and in nodularin-containing cell-free extracts
      and whole filaments of the nodularin-producer, Nodularia spumigena in sunlight
      and darkness. Levels of purified nodularin in aqueous solution remained
      approximately constant throughout the 9-day trials under all conditions, but
      decreased in cell-free extracts and whole filaments when incubated under all
      conditions, with losses being greatest in full sunlight, intermediate in sunlight
      minus ultraviolet wavelengths and lowest in continuous darkness. Photodegradation
      and detoxification in Artemia salina bioassays occurred when purified nodularin
      was irradiated with ultraviolet wavelengths using a laboratory lamp.

PMID- 9198287
TI  - Palmitoyl carnitine, a lysophospholipase-transacylase inhibitor, prevents Candida
      adherence in vitro.
AB  - Candida adherence is poorly understood. The results of this study indicate that
      interactions of Candida with the lyso-forms of phospholipids may be one important
      attachment mechanism. C. tropicalis and C. albicans adhered to purified
      lysophospholipids immobilized on microtiter wells, as well as to a human
      laryngeal epidermoid carcinoma (HEp-2) cell line. Adherence to both
      lysophospholipids and HEp-2 cells was significantly reduced by palmitoyl
      carnitine, a lysophospholipase-transacylase inhibitor. Over time there was a
      positive correlation between Candida adherence and its transacylase activity. The
      data suggest that palmitoyl carnitine interferes with Candida adherence to
      lysophospholipids and the HEp-2 cell line by blocking the interaction between the
      Candida-associated transacylase enzyme receptor site and its lysophospholipid
      substrate ligand.

PMID- 9198288
TI  - Hyperdynamic circulation in prehepatic portal hypertension: role of tumor
      necrosis factor-alpha.
AB  - BACKGROUND: Portal hypertension is associated with a hyperdynamic circulation
      characterized by increased cardiac output and reduced systemic vascular
      resistance. Tumor necrosis factor-alpha (TNF-alpha) is a peptide mediator
      released by mononuclear cells on activation by endotoxin, tissue injury and
      malignancy. This cytokine induces vasodilatation by activating nitric oxide
      synthesis. The aim of this study is to investigate if TNF-alpha is involved in
      the pathogenesis of hyperdynamic circulation observed in portal vein-ligated
      (PVL) rats. METHODS: Systemic and portal hemodynamics were determined in seven
      PVL and five sham-operated (SHAM) rats using a thermodilution technique. In
      addition, plasma TNF-alpha concentrations were determined in another 34 PVL and
      16 SHAM rats using commercially available enzyme-linked immunosorbent assay.
      RESULTS: PVL rats had a significantly lower mean arterial pressure (109 +/- 17
      mmHg vs. 133 +/- 12 mmHg, p < 0.001) and systemic vascular resistance (2.5 +/-
      0.6 mmHg.ml-1.min.100 g BW vs. 4.6 +/- 0.8 mmHg.ml-1.min.100 g BW, p < 0.001)
      accompanied by a significantly higher portal pressure (14 +/- 1.9 mmHg vs. 9 +/-
      2.1 mmHg, p < 0.001) and cardiac index (47.0 +/- 12.1 ml.min-1.100 g BW-1 vs.
      29.3 +/- 3.5 ml.min-1.100 g BW-1, p < 0.001) when compared with SHAM rats. Also,
      PVL rats had significantly higher plasma levels of TNF-alpha as compared with
      SHAM rats (13.8 +/- 0.9 pg/ ml vs. 11.1 +/- 0.5 pg/ml, p < 0.05). CONCLUSIONS:
      This study suggests that elevated plasma levels of TNF-alpha observed in PVL rats
      may participate in the development and/or maintenance of the hyperdynamic
      circulation occurring in prehepatic portal hypertension.

PMID- 9198289
TI  - Transitional cell and uncommon urothelial carcinoma of renal pelvis/ureter and
      bladder: low incidence of human papilloma virus.
AB  - BACKGROUND: Recently, it has been proposed that human papilloma virus (HPV)
      infection may play a role in the carcinogenesis of bladder urothelial malignancy.
      However, there is still controversy about the prevalence of HPV in such
      malignancies. With similar techniques of in situ hybridization (ISH) or
      polymerase chain reaction (PCR), either high or rare frequency have been
      detected. To evaluate the prevalence of HPV in the urothelial malignancies based
      on presentations here, 118 cases of urothelial malignancies were analysed,
      including those of the renal pelvis and ureter which have rarely been reported
      before. METHODS: Non-isotopic ISH technique was used to detect HPV on paraffin
      sections, including 51 bladder transitional cell carcinoma (TCC), 48 renal
      pelvic/ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell carcinoma, 2
      bladder undifferentiated carcinoma, 1 multiple synchronous pelvic and ureteric
      squamous cell carcinoma (SCC) and 8 bladder SCC. An FITC-labelled probe of wide
      spectrum HPV was used for screening, and probes of HPV 6/11, 16, 18, 31, 33 were
      used for typing. RESULTS: By the technique of ISH, wide spectrum HPV was detected
      in only three of the eight cases of bladder SCC. Of the three positive cases, two
      were subsequently shown to be uterine cervical SCC with bladder invasion.
      Therefore, HPV was positive in only one case of primary bladder SCC, occurring in
      a patient with systemic lupus erythematosus under steroid and cyclophosphamide
      therapy. Further subtyping was negative for HPV 6/11, 16, 18, 31, and 33. The
      result indicated that the positive staining by wide spectrum probe was caused by
      types 30, 35, 45, 51, and/or 52. HPV was not detected in any of the 51 bladder
      TCC, 48 renal pelvic/ ureter TCC, 5 bladder adenocarcinoma, 3 bladder small cell
      carcinoma, and 2 bladder undifferentiated carcinoma. CONCLUSIONS: The results are
      in agreement with the majority of recent reports which suggest that HPV is
      unlikely to be involved in the etiology of urothelial malignancies; however, it
      seems probable that immunosuppressed patients are at greater risk for HPV
      associated bladder SCC.

PMID- 9198290
TI  - Diagnostic laparoscopy: indication and benefit.
AB  - BACKGROUND: Patients with an obscure and unrelievable abdominal condition may be
      forced to receive open laparotomy for diagnosis. Diagnostic laparoscopy has been
      suggested as an alternative to diagnostic laparotomy in selected cases. The aim
      of this article is to evaluate the circumstances suitable for laparoscopic
      diagnosis of certain abdominal conditions and the possible advantages of that
      approach. METHODS: Among 256 patients undergoing elective laparoscopic operations
      using conventionally pneumoperitoneal techniques from January 1994 to June 1995,
      twenty patients received diagnostic laparoscopy. The correlation between
      preoperative diagnosis, laparoscopic diagnosis and pathologic diagnosis as well
      as the outcome of laparoscopic diagnosis and treatment have been assessed.
      RESULTS: Major indications for diagnostic laparoscopy included acute abdominal
      pain (n = 4), chronic abdominal pain (n = 6), differentiating intraabdominal
      tumor (n = 4), staging known malignancy (n = 3) and evaluating intraperitoneal
      implantation (n = 3). Two of the four patients with acute abdominal conditions,
      one of the six patients with chronic abdominal pain. Four of the seven patients
      with undifferentiated/unstaged abdominal tumors and all of the three patients
      with intraperitoneal-implanted drainage tubes had no reasons for a further
      exploratory procedure, thus preventing the morbidity or mortality which might
      occur after unnecessary laparotomy. The duration of operation and hospitalization
      was shorter than the group without laparotomy. CONCLUSIONS: Diagnostic
      laparoscopy benefits patients by avoiding unnecessary surgery, avoiding
      unnecessary delay in diagnosis and treatment and shortening the operative and
      hospitalized period. However, it provides only an alternative not a substitute
      for traditional diagnostic procedures and will never lessen the importance of
      conventional laparotomy.

PMID- 9198291
TI  - Refined fetal abdominal growth assessment in normal pregnancy: Part I. Abdominal
      anteroposterior diameter.
AB  - BACKGROUND: The assessment of the adequacy of fetal growth by parameters other
      than the abdominal anteroposterior diameter (AAPD) of the fetus has been studied
      extensively. However the designs of these studies and the statistical methods
      used appears to deserve some criticism, based on present knowledge. Noncross
      sectional cases selection, uncertainty of the fetal normality and inadequacy in
      statistical method, mostly ignored the changing property of each standard
      deviation (SD) of each gestational age (GA) which was proposed by Altman et. al.
      in 1993, are the three most common flaws in previous publishes. We tried to use
      AAPD with a strict study design as well as a reasonable statistical method to
      evaluate the fetal growth. METHODS: This study was performed in the Division of
      Maternal Fetal Medicine, National Cheng Kung University Hospital, Taiwan. The
      prenatal sonographic data of the fetuses were collected prospectively based on
      the following criteria: (1) accurate dating by knowing the maternal last
      menstration period (LMP) and early ultrasonography of the fetuses, (2) singleton
      pregnancy, (3) no fetal structural or chromosomal abnormality confirmed by
      prenatal ultrasonography and postnatal examination, (4) GA at birth was between
      37 and 41 weeks' gestation, (5) no birth asphyxia, (6) appropriate birth body
      weight, and (7) no maternal medical disease or obstetrical complication which
      might predictably interfere with fetal growth. The collected data were analyzed
      by polynomial regression test and the best-fit equation for prediction of fetal
      growth was selected. The standard deviation (SD) of each GA was modeled before
      constructing the fetal growth centile charts by Altman's method. RESULTS: A total
      of 2077 cross-sectional sonographic data meeting the above criteria were
      collected for statistical analysis. The best-fit equation for the prediction of
      fetal GA by AAPD is GA = 20.8539 - 3.36743 x AAPD + 0.86927 x (AAPD)2 - 0.03789 x
      (AAPD)3 +/- k x [1.2533 x (0.36772 + 0.10938 x AAPD)], (r = 0.97287, p < 0.0001).
      The best-fit equation for prediction of fetal AAPD by GA is AAPD = -2.49495 +
      0.38247 x GA - 1.07071 x 0.001 x (GA)2 +/- k x [1.2533 x (0.01760 + 0.01372 x
      GA)], r = 0.97122, p < 0.0001. The SD of AAPD for each complete GA was not the
      same. The fetal growth centile charts in the study are presented in this article.
      CONCLUSIONS: The SD of each complete GA changed with each specific GA. The GA of
      the fetus can be assessed accurately by measuring the AAPD alone. The utilization
      of these growth centile charts for evaluation of fetal growth is recommended.

PMID- 9198292
TI  - Clarithromycin in the combination therapy for the eradication of Helicobacter
      pylori in peptic ulcer disease.
AB  - BACKGROUND: Clarithromycin is a new macrolide antibiotic which is known to be
      highly effective in eradicating Helicobacter pylori (H. pylori). In Chinese, the
      role of clarithromycin for H. pylori is still unclear. METHODS: Between January
      1995 and February 1996, 75 patients with active H. pylori-positive duodenal ulcer
      were enrolled in this study. Three groups were randomized to have (1) 2 x 150 mg
      nizatidine twice daily, 2 x 250 mg amoxicillin four times daily, and 2 x 250 mg
      clarithromycin three times daily for two weeks (niz-amox-clar group, N = 25); or
      (2) 20 mg omeprazole twice daily plus 2 x 250 mg clarithromycin three times daily
      for two weeks (ome-clar group, N = 25); or (3) 300 mg bismuth subsalicylate four
      times daily, and 2 x 250 mg amoxicillin four times daily, 250 mg metronidazole
      four times daily for two weeks (triple therapy group, N = 25). All the patients
      received H2 receptor antagonist (150 mg nizatidine or ranitidine, or 400 mg
      cimetidine, twice daily) for the consecutive six weeks. RESULTS: The eradication
      rate of H. pylori eight weeks after the entry of study was 80%(20/25) in the niz
      amox-clar group, 76%(19/25) in the ome-clar group, 88%(22/25) in the triple
      therapy group (p < 0.05 among the three groups). The ulcer healing rates eight
      weeks after the entry of study for the niz-amox-clar, the ome-amox, and the
      triple therapy groups were 84%(21/25), 80%(20/25), and 80%(20/25), respectively
      (p < 0.05 among the three groups). The number of patients experiencing adverse
      effects in the niz-amox-clar group, the ome-clar group, and the triple therapy
      group were 10(40%), 7(28%), and 4(16%), respectively (p > 0.05 among the three
      groups). CONCLUSIONS: Both nizatidine/amoxicillin/clarithromycin and
      omeprazole/clarithromycin regimens can achieve good eradication rates and may
      provide an effective alternative anti-H. pylori treatment in duodenal ulcer
      diseases.

PMID- 9198293
TI  - Prognostic factors affecting long-term survival after partial hepatectomy for
      human hepatocellular carcinoma.
AB  - BACKGROUND: Various prognostic factors have been studied during the past few
      years to predict early tumor recurrence and survival in patients undergoing
      hepatectomy for primary hepatocellular carcinoma. However, the relationship
      between these factors and long-term survival has not been clarified. The purpose
      of this study was to identify the factors linked to long-term prognosis in
      patients with resectable hepatocellular carcinoma after hepatectomy. METHODS:
      Records of 370 patients undergoing curative hepatectomy during a period from July
      1981 to July 1994 were retrospectively reviewed. Only 110 patients with disease
      free survival > or = 36 months were eligible for long-term survival analysis.
      Their further outcomes, including disease-free survival and overall survival,
      were analyzed in correlation with various prognostic factors by Kaplan-Meier's
      method, log rank test; and Cox's regression model. Analysis of prognostic factors
      linked to early tumor recurrence after curative hepatectomy was also performed in
      324 patients who were followed up > or = 12 months. RESULTS: Tumor behaviors were
      found to be the principal prognostic factors determining the early tumor
      recurrence and patients' survival (p < 0.05). However, when long-term survival
      was analyzed, the pathological status of the liver remnant such as the presence
      or absence of hepatitis B virus infection, chronic active hepatitis, hepatocyte
      dysplasia and age (< or = 60 y/o vs. > 60 y/o), as well as preoperative liver
      function (total serum bilirubin < or = 1.5 mg/dl vs. > 1.5 mg/dl), were found to
      make significant disease-free survival differences (p < 0.05), whereas the
      factors linked to tumor behaviors and surgical factors showed no influence on
      long-term prognosis. CONCLUSIONS: Pathological status and host factors (age and
      liver function) have effect upon long-term prognosis after hepatic resection for
      hepatocellular carcinoma.

PMID- 9198294
TI  - Diagnosis of left atrial thrombus with the aid of transesophageal
      echocardiography during aortic valve replacement: a case report.
AB  - Transthoracic echocardiography and cardiac angiography are the most common tools
      used in this hospital for evaluation of cardiac disease. Yet the specificity of
      either method in detection of left atrial pathologies is unsatisfactory. In a 76
      year-old male, severe aortic regurgitation with congestive heart failure was
      impressed from preoperative studies including transthoracic echocardiography and
      cardiac angiography. However, left atrial thrombus was further detected during
      routine intraoperative transesophageal echocardiography. Surgical evacuation of a
      left atrial thrombus was done before undertaking aortic valve replacement. The
      timely finding was crucial for prevention of further complication and for
      expeditious use of definite therapy.

PMID- 9198295
TI  - Successful surgical treatment of bilateral congenital chylothorax: a case report.
AB  - A male infant was diagnosed at 19 days old to have a right chylothorax.
      Conservative management, including median-chain triglyceride (MCT) diet, total
      parenteral nutrition (TPN) and chyle drainage, were unsuccessful. The boy
      received a right thoracotomy with ligation of the thoracic duct and sutures of
      leaking lymphatic ducts at the age of 65 days. The result of the operation was
      satisfactory but left chylothorax developed six days later. Left thoracotomy was
      performed eight days later to suture the leaking lymphatic chains and finally the
      patient recovered well. Followed for one year, the patient's physical development
      was satisfactory. Prompt surgical intervention for congenital chylothorax is
      strongly recommended, if medical treatment fails.

PMID- 9198296
TI  - Transcatheter embolization of coronary artery fistula: a case report.
AB  - Coronary artery fistula is rare, but it is the most common congenital coronary
      artery anomaly with hemodynamic significance. It usually causes no symptoms in
      young patients but may be associated with symptoms and complications in older
      patients. Surgery has been the traditional treatment. In this report, a 7-year
      old girl who had a coronary artery fistula from the left circumflex coronary
      artery to the right atrium was successfully treated by percutaneous transcatheter
      technique.

PMID- 9198297
TI  - Cockayne syndrome with tetralogy of Fallot: a case report.
AB  - Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by
      growth retardation, senile-like appearance, loss of subcutaneous adipose tissue,
      photosensitive dermatitis, microcephaly, deafness, pigmentary degeneration of
      retina, disproportionately long limbs, skeletal malformations with knee
      contractures and neurologic abnormalities. This is a description of a three-year
      old boy with typical features of Cockayne syndrome complicated with tetralogy of
      Fallot, pneumonia and hepato-splenomegaly. He had been suffering from frequent
      attacks of pneumonia and had been hospitalized for several times since birth.
      Tetralogy of Fallot was diagnosed under echocardiography study and he died
      suddenly in hospital during a mydriatic procedure in the Ophthalmologic Clinic.

PMID- 9198298
TI  - Gastric adenocarcinoma with microangiopathic hemolytic anemia and disseminated
      intravascular coagulation: a case report.
AB  - The case reported was a 54-year-old woman with adenocarcinoma of the stomach who
      developed microangiopathic hemolytic anemia (MHA) and disseminated intravascular
      coagulation (DIC). Clinical and laboratory data pertaining to this patient are
      presented. The patient died of multiple organ failure on the 12th hospital day.
      Since 1962, a total of 96 cases of MHA occurring in patients with malignancy have
      been reported. About half of them occurred in patients with gastric carcinoma.
      The possible pathogenesis of MHA and disseminated intravascular coagulation in
      patients with gastric adenocarcinoma is discussed.

PMID- 9198299
TI  - Traumatic dissection of the vertebral artery: a case report.
AB  - This report concerns a patient suffering from a severe neck pain on the third day
      after a traffic accident. This condition was followed by a lateral medullary
      infarction on the next day. One week later, he was transferred to this hospital
      and dissection of the vertebral artery was disclosed. It should be emphasized
      that in case of acute cervical spine injury or severe neck pain after a major
      trauma, vertebral artery dissection should be considered, as its early diagnosis
      may have crucial therapeutic implications. In addition, the advantages of the
      combination of magnetic resonance imaging and magnetic resonance angiography as
      diagnostic tools-of-choice are emphasized.

PMID- 9198300
TI  - Diphtheria acquired during a cruise in the Baltic Sea.

PMID- 9198301
TI  - Developing a standard enhanced surveillance system for food poisoning.

PMID- 9198302
TI  - Infections with Corynebacterium diphtheriae--changing epidemiology and clinical
      manifestations. Report of the third international meeting of the European
      Laboratory Working Group on Diphtheria (ELWGD), Institute Pasteur, Paris 7-8 June
      1996.
AB  - A widespread epidemic of diphtheria began in 1990 in the former Soviet Union, in
      the context of falling immunisation rates and social disruption. Control was
      impeded by limited diagnostic resources in affected countries (mainly Russia) and
      there was a risk of spread to neighbouring countries. The European Laboratory
      Working Group on Diphtheria (ELWGD) was formed to assist in control of the
      epidemic. The ELWGD is convened by the Public Health Laboratory Service in the
      United Kingdom and includes 15 laboratories in Europe, one in North America
      (Centers for Disease Control and Prevention) and the Institute of Clinical
      Pathology and Medical Research, Sydney. At the group's last annual meeting in
      Paris, reports were presented on the progress of the epidemic, control strategies
      and improvements in laboratory diagnosis. The group discussed the increased
      carriage of, and infection with, nontoxigenic Corynebacterium diphtheriae in
      countries with high immunisation rates, including the United Kingdom and
      Australia. They also considered the possible relationship between this increase
      and the continued diphtheria outbreak in eastern Europe. Preliminary results of
      molecular typing of toxigenic and nontoxigenic isolates from many parts of the
      world were presented. It was agreed that further epidemiological investigation is
      required, using a standardised ribotyping system.

PMID- 9198303
TI  - Diphtheria--the Australian perspective.

PMID- 9198304
TI  - National Health and Medical Research Council recommendations on diphtheria
      vaccination.

PMID- 9198305
TI  - Communicable diseases surveillance.

PMID- 9198306
TI  - Genetic drift and gene flow in post-famine Ireland.
AB  - This study examines the genetic impact of the Great Famine (1846-1851) on the
      regional genetic structure of Ireland. The Great Famine resulted in a rapid
      decrease in population size throughout Ireland in a short period of time,
      increasing the possibility of genetic drift. Our study is based on migration and
      anthropometric data collected originally in the 1930s from 7211 adult Irish
      males. These data were subdivided into three time periods defined by year of
      birth: 1861-1880, 1881-1900, and 1901-1920. Within each time period the data were
      further subdivided into six geographic regions of Ireland. Estimates of Wright's
      FST were calculated from parent-offspring migration data and from 17
      anthropometric variables (10 head measures, 7 body measures). Over time, the
      average population size decreased, but average rates of migration increased. The
      estimates of FST at equilibrium from migration matrix analysis suggest that the
      net effect of these opposite effects is a reduction in among-group variation.
      Closer examination shows that within each time period the rate of convergence to
      equilibrium is slow, meaning that the expected levels of genetic homogeneity
      revealed from migration matrix analysis are not likely to be seen over short
      intervals of time. Estimates of FST from anthropometric data show either
      relatively little change in microdifferentiation or some increase, depending on
      which variables are analyzed. Investigation of a simple model of demographic and
      genetic change shows that, given the demographic changes in post-Famine Ireland,
      FST could in theory increase, decrease, or remain the same over short intervals
      of time. Overall, the Great Famine appears to have had minimal impact on the
      genetic structure of Ireland on a regional level. Comparison with studies
      focusing on local genetic structure shows the opposite. It appears that the level
      of genetic impact depends strongly on the level of analysis; local populations
      are affected to a greater extent by demographic shifts than regional populations.
      We also provide formulas for the standard errors of FST from metric traits and
      related statistics.

PMID- 9198307
TI  - Tracing prehistoric migrations by the viruses they carry: human T-cell
      lymphotropic viruses as markers of ethnic relationships.
AB  - Three reasons that HTLV-I and HTLV-II would not be expected to trace human
      migrations over extended time periods have been examined, and none has proven
      fatal to the theory. Transmission of the HTLVs (human T-cell lymphotropic
      viruses) in endemic settings highly depends on passage through breast milk, and
      this creates a pattern of distribution similar to that of mitochondrial DNA. The
      HTLVs probably evolve at variable rates, making the extent of sequence change a
      poor tool for dating human migrations. However, qualitative relationships between
      the sequence of human population separations and virus strain may be more
      regular. The uniqueness of viruses as markers of human relationship gives this
      method special value as a source of novel ideas regarding human movements and as
      independent confirmation of migration hypotheses that have been based on more
      conventional methods.

PMID- 9198308
TI  - Study of the populations of the Balearic Islands (Spain) using mtDNA RFLPs.
AB  - The Balearic archipelago (Spain) is composed of three major islands, Majorca,
      Minorca, and Ibiza. Majorca is the largest and most populous island. Minorca is
      the second largest in area and third in population, and Ibiza is the smallest of
      the three and has the second largest population. Ibiza also shows differences
      from the other two islands in its landscape, vegetation, and especially origins
      of the founding settlements. The three islands also have been settled by people
      of different cultures. We have carried out a genetic analysis at the level of
      mtDNA RFLPs in these populations and found that the three populations are
      genetically structured, with differences in the RFLP haplotype frequencies
      reflecting the different population substrata of the three islands. In this
      structure Ibiza is genetically more different from Majorca and Minorca. In
      addition, we found a new haplotype in Minorca, named haplotype 150, which seems
      to originate from haplotype 56.

PMID- 9198309
TI  - Cystic fibrosis in the Brazilian population: DF508 mutation and KM-19/XV-2C
      haplotype distribution.
AB  - We have used PCR amplification of DNA obtained from Guthrie cards to identify the
      DF508 mutation and correlate it with the allele frequencies at two polymorphic
      loci (XV-2C and KM-19) closely linked to the cystic fibrosis gene. The DNA came
      from 193 white Brazilian families affected by cystic fibrosis and living in five
      different states of Brazil. The distribution of the haplotypes derived from the
      DF508 and non-DF508 XV-2C/KM-19 genotypes indicates that 88% of the DF508 alleles
      are linked to haplotype B and suggests that high heterogeneity exists among the
      non-DF508 cystic fibrosis alleles occurring in different states. Our data can be
      used to compare linkage disequilibrium between Brazilians and other heterogeneous
      populations where the DF508 mutation frequency is low and where many different
      rare mutations account for the remaining recessive cystic fibrosis alleles.

PMID- 9198310
TI  - Low-molecular-weight acid phosphatase (ACP1), obesity, and blood lipid levels in
      subjects with non-insulin-dependent diabetes mellitus.
AB  - Low-molecular-weight acid phosphatase (ACP1) is a polymorphic protein-tyrosine
      phosphatase present in all human tissues, including adipocytes. A positive
      association between the low-activity ACP1*A/*A genotype and extreme body mass
      index has previously been shown by us in obese subjects from the population of
      Rome. We have now studied a sample of 265 subjects with non-insulin-dependent
      diabetes mellitus (NIDDM) from another Italian population. There is a significant
      interaction between ACP1, body mass index, and blood lipid level. A highly
      significant positive association between ACP1*A/*A and high body mass index
      similar to that previously observed in obese subjects from the population of Rome
      is present only in those NIDDM subjects with blood lipid levels within the normal
      range. In NIDDM subjects the low-activity ACP1*A/*A variant seems to favor the
      increase of body mass or blood lipid levels or both. The pattern of association
      is independent of sex, age at survey, age at onset of diabetes, duration of
      disease, and therapy.

PMID- 9198311
TI  - Evolution of consanguinity in the Archbishopric of Santiago de Compostela (Spain)
      during 1900-1979.
AB  - We present a study of the frequencies of the different types of consanguineous
      marriages, up to the level of second cousins, using as a source the
      ecclesiastical dispensations given from 1900 to 1979 in the Archbishopric of
      Santiago de Compostela (Galicia, Spain). We also report the rate of
      consanguinity, the average coefficient of inbreeding, and its evolution. From
      1900 to 1979, 15,739 consanguineous marriages were registered, corresponding to
      25 different categories of relationship. The rate of consanguinity of the total
      number of consanguineous marriages is 5.13% and the average coefficient of
      inbreeding is 1.94 x 10(-3), values that are within the wide range of variability
      found in other Spanish populations. Spain is characterized, with regard to the
      rest of Western Europe, by a high level of inbreeding with a late and rapid
      decrease in this factor. The most relevant aspect of the structure of
      consanguinity lies in the high frequency of marriages between close relatives:
      0.16% uncle-niece or aunt-nephew marriages and 1.62% marriages between first
      cousins, both values with respect to the total number of marriages. This
      phenomenon appears to be generalized throughout northern Spain. The evolution of
      the total consanguinity lends itself to a polynomial curve model. The fitted
      curve of the evolution of the average coefficient of inbreeding has an ascending
      branch and a descending branch, with the inflection point situated in the year
      1918; the regression lines, for both the ascending and the descending branches,
      have regression coefficients significantly different from 0 (p < 0.001).

PMID- 9198312
TI  - Nativity, race, and mortality: influence of region of birth on mortality of US
      born residents of New York City.
AB  - Among non-Hispanic black and white residents of New York City the association
      between birthplace by region (South, West/ Midwest, and Northeast) within the
      United States and mortality was determined by linking mortality records for 1988
      1992 with the 1990 United States census data for New York City. Age-adjusted
      death rates computed by birthplace for blacks and whites were examined and also
      compared with total US data. The results indicate that death rates for New
      Yorkers generally exceed those of the United States overall, and black rates
      exceed those of whites. Moreover, Southern-born blacks have substantially higher
      death rates than do blacks born in the Northeast. The most striking variations
      are for cancer and diseases of the heart. Deaths from AIDS and homicide are
      higher among blacks than among whites, but the rates for Southern-born blacks do
      not exceed those for Northeastern-born blacks. For whites those born in the South
      have higher death rates overall than those born in the Northeast, but differences
      in cause-specific mortality are less consistent than for blacks. The results
      reveal substantial heterogeneity of health status based on nativity, among blacks
      in particular. To understand the role of the related factors, both genetic and
      environmental, further population and epidemiologic studies are important.

PMID- 9198313
TI  - Offspring sex ratio in women with android body fat distribution.
AB  - The relationship between waist-to-hip ratio (WHR), several behavioral factors,
      and the number of male and female offspring was examined in a sample of 69 women.
      Two questions were examined: (1) Are hormonal differences, as indicated by
      differences in the WHR, associated with offspring sex ratio? and (2) are there
      any behavioral factors, such as coital frequency or orgasm, that are associated
      with offspring sex ratio? After statistically controlling for subject's age,
      socioeconomic status, and total number of offspring, we found that women with a
      higher WHR tended to have more sons than daughters. In addition, women who
      reported greater ease of having multiple orgasms also tended to have more sons
      than daughters. The results thus support both a hormonal and a behavioral
      influence on offspring sex ratio.

PMID- 9198314
TI  - Determinants of breast-feeding patterns in an urban society of India.
AB  - Breast feeding is the focus of rapidly growing interest in many areas of
      demographic research. However, relatively few rigorous studies on breast-feeding
      patterns and correlates in contemporary India have been published. This study
      uses data from a retrospective survey conducted in 1991-1992 to investigate
      current breast-feeding patterns and to identify the key factors that influence
      the duration of exclusive breast feeding and infant's age at the time of weaning
      in an urban Hindu society of the northeast Indian state of Assam. Applying life
      table procedures and a hazards regression model, we found evidence that the
      median duration of exclusive breast feeding and infant's age at the time of
      weaning were negatively associated with mother's education, per capita income,
      and social status of the household. Those infants who were breast-fed longer at
      night than in the daytime were also at greater risk of earlier introduction of
      non-breast-milk foods and of earlier termination of breast feeding than infants
      who were breast-fed longer during the day. Gender bias toward males in rearing
      infants prevails in this urban society, and male infants were found to have a
      significantly lower risk of early weaning than female infants.

PMID- 9198315
TI  - High frequency of the apolipoprotein E *4 allele in African pygmies and most of
      the African populations in sub-Saharan Africa.
AB  - Apolipoprotein E genotypes (alleles *2, *3, and *4) have been determined in 70
      Aka Pygmies and 470 unrelated African sub-Saharan subjects. Allele frequencies
      for Pygmies are 5.7% for APOE*2, 53.6% for APOE*3, and 40.7% for APOE*4, and the
      global proportions for sub-Saharan subjects are 11.6% for APOE*2, 70.6% for
      APOE*3, and 17.8% for APOE*4. The frequencies in some ethnic groups are
      statistically different from the overall mean in the Afar and the Isa, the Ewe
      (Togo), the Malinke (Guinea), and the Mossi; three ethnic groups have a higher
      allele frequency of APOE*4 (Fon, 29.4%; Zairians, 33.3%; Tutsi, 38.5%). The
      APOE*4 allele is considered the ancestral form because of its high frequency in
      African Pygmies and other aboriginal populations.

PMID- 9198316
TI  - Melkersson-Rosenthal syndrome--a challenge for dermatologists to participate in
      the field of oral medicine.
AB  - Melkersson-Rosenthal syndrome (MRS) is a neuro-muco-cutaneous disorder involving
      remittently both the oro-facial innervation and muco-cutaneous tissues in a
      pathosis of complex origin characterized by recurrent edema, facial or other
      palsies, and nerval dysfunctions frequently associated with plicated tongue.
      Biopsies taken from the edematous tissues often reveal a temporary pattern of
      moderate epitheloid granulomatous inflammation scattered scarcely within
      remarkable tissue edema. However, this histological pattern is not a prerequisite
      for the diagnosis of MRS. The disease usually runs an intermittent and
      unpredictable course over years or decades and may have, if the edemas involve
      the tongue or the central nervous system, an ambiguous outcome. Greatly
      disfiguring oro-facial swellings often result from secondary persistence of the
      primarily recurrent edemas. A classification on grounds of different 'major' and
      'minor signs' of MRS is proposed in the present paper. In recent years, novel
      therapeutic approaches involving either oral clofazimine or laser beam
      acupuncture (according to the principles of traditional Chinese medicine) have
      proven to be successful in some cases of MRS. Dermatology could play a larger
      role in oral medicine by taking diseases such as MRS into account in studies
      among specialties dealing with oro-facial pathoses.

PMID- 9198317
TI  - The comparative study of anti-double stranded DNA antibody levels measured by
      radioimmunoassay and enzyme-linked immunosorbent assay in systemic lupus
      erythematosus.
AB  - Anti-double stranded (ds) DNA antibody is an autoantibody specific for systemic
      lupus erythematosus (SLE). For the measurement of this antibody, radioimmunoassay
      (RIA) or enzyme-linked immunosorbent assay (ELISA) is widely used in Japan. We
      studied the correlation of anti-dsDNA levels in 158 sera from 53 SLE patients
      between RIA and ELISA. The correlation coefficient between anti-dsDNA antibody
      levels measured by RIA and ELISA was 0.736 (p < 0.001). The concordance rate of
      sera with both ELISA/RIA-positive or both ELISA/RIA-negative results was 82.3%
      (130/158 sera). Twenty sera (12.7%) of 14 patients were ELISA-positive but RIA
      positive, and 8 sera (5.0%) of 6 patients were ELISA-negative but RIA-positive.
      Our results suggest that both methods may be equally reliable for the detection
      of anti-dsDNA antibodies and that ELISA may be more sensitive than RIA. ELISA may
      be preferable because of its simplicity and convenience of the measurement
      procedure. The correlation coefficient between anti-ssDNA levels measured by
      ELISA and anti-dsDNA levels measured by RIA was 0.322 (p < 0.01), and the
      correlation coefficient between anti-ssDNA and anti-dsDNA antibody levels
      measured by ELISA was slightly higher, 0.515 (p < 0.001). These results may
      reflect the predominance of anti-DNA antibodies reactive with both ss and dsDNA
      in SLE sera. Since the clinical significance of anti-ssDNA antibodies remains
      unclear, further analysis of accumulated cases is required.

PMID- 9198318
TI  - OK-432 therapy for recalcitrant warts.
AB  - Twelve patients with warts recalcitrant to various treatment, including
      cryotherapy, were treated with OK-432 injection therapy. Six patients received
      only subcutaneous injection, three received only intralesional injection, and the
      other three received both subcutaneous and intralesional injections. Complete
      clearing of the warts occurred in nine (75%) of 12 patients, while the other
      three patients were not cured. Grouping the patients by the method of injection,
      the success rate of subcutaneous injection was 5/9 (55.6%), and that of
      intralesional injection was 4/6 (66.7%). Although five patients complained of
      mild fever and malaise, these side effects gradually disappeared during the
      repeated injections. OK-432 injection is considered as a hopeful therapy for
      recalcitrant warts.

PMID- 9198319
TI  - A case of linear IgA disease: an immunofluorescent study using confocal laser
      scan microscopy.
AB  - A 79-year-old Japanese woman presented with erythema and bullae on her trunk and
      limbs. Histological examination of the skin lesions showed subepidermal bullae
      and polymorphonuclear leukocyte infiltration into the papillary dermis. A direct
      immunofluorescent study showed the linear deposition of IgA, but not of IgG or
      IgM, in the basement membrane zone. Indirect immunofluorescence of the serum
      using confocal laser scan microscopy showed IgA, but not IgG, reactivity in the
      basement membrane zone. In double immunostaining experiments, IgA reactivity was
      also observed on the epidermal side; laminin 5 was detected on the dermal side.

PMID- 9198320
TI  - Merkel cell carcinoma and multiple Bowen's disease: incidental association or
      possible relationship to inorganic arsenic exposure?
AB  - An 81-year-old Japanese male was referred to our clinic in 1991 with multiple
      Bowen's disease. The associated hyperpigmentation of the trunk and extremities
      and palmoplantar keratotic nodules indicated that he had suffered from chronic
      arsenic poisoning. Interestingly, he was a native of Namikata in Ehime, Japan,
      where many residents have suffered from multiple Bowen's disease with internal
      malignancy. Arsenic exposure was strongly suspected. Two years later, Merkel cell
      carcinoma developed on the dorsum of his right hand, where Bowen's disease
      lesions were absent. Metastasis of this Merkel cell carcinoma led to his eventual
      death one year later. To our knowledge, this is the first report of Merkel cell
      carcinoma associated with multiple Bowen's disease. Chronic arsenic poisoning may
      be responsible for the association of these two rare skin neoplasms.

PMID- 9198321
TI  - Giant basal cell carcinomas: report of four cases and considerations.
AB  - Four cases of giant basal cell carcinoma (BCC) are reported and the problems of
      giant BCCs are briefly discussed. In particular, we consider the relationship
      between the size of the tumor and its clinical behaviour. The importance of the
      site location in tumor development the histologic subtypes involved, the
      associated findings, and problems of treatment are also discussed.

PMID- 9198322
TI  - Two cases of basal cell carcinoma arising in seborrheic keratosis.
AB  - The present study reports two cases of basal cell carcinoma arising in seborrheic
      keratosis. The first case is a seventy-three-year-old female who presented with a
      blackish nodule arising from a pigmented lesion on her chest. Histopathological
      analysis of the nodule and the pigmented lesion revealed a basal cell carcinoma
      with hair follicular differentiation and an acanthotic seborrheic keratosis,
      respectively. The second case is a seventy-year-old female with a blackish nodule
      arising from a pigmented lesion on her back. Histological analysis of the nodule
      revealed an atypical basaloid cell mass surrounded by a seborrheic keratosis
      lesion. In addition to the coexisting seborrheic keratosis with the basal cell
      carcinoma, a basaloid follicular hamartoma that showed multiple hamartomatous
      hair follicles or small cysts replaced by a branching cord or lace-like network
      of basaloid cells surrounded by fibrovascular stroma was identified. We concluded
      that both cases presented a rare combination of a seborrheic keratosis which
      underwent a malignant change to basal cell carcinoma. It appears that both basal
      cell carcinomas and seborrheic keratosis may derive from a similar source:
      pluripotential cells of either the epidermis or hair follicle epithelium.

PMID- 9198323
TI  - Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular
      elastolytic giant cell granuloma.
AB  - A 72-year-old fisherman who was positive for the HCV antibody developed an
      annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were
      diagnosed as annular elastolytic giant cell granuloma both clinically and
      histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for
      several months failed to improve the lesions. We then started dapsone, a known
      anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous
      lesions faded, and the infiltration gradually decreased. No recurrence has been
      observed for one year after the start of the therapy. Anti-oxidative therapy
      appears to be effective for annular elastolytic giant cell granuloma and could be
      an alternate therapy for refractory granulomatous disease.

PMID- 9198325
TI  - A case of multiple nevoid hypertrichosis.
AB  - Nevoid hypertrichosis is an uncommon congenital disorder consisting of terminal
      hair growth in a localized distribution on flesh-colored skin; it is not
      associated with any other systemic abnormalities. A 21-year-old male patient had
      a circumscribed area of depigmented terminal hairs on his chest which had been
      present since 1 year of age. At the age of 18, similar lesions developed on his
      left shoulder and upper arm. The underlying skin was slightly hypopigmented, and
      no other systemic abnormalities were found. Histologic examination demonstrated
      terminal hair follicles in otherwise normal skin. The number of HMB 45 positive
      melanocytes was markedly decreased in the affected skin. This case of multiple
      nevoid hypertrichosis is reported with a review of previously reported cases.

PMID- 9198324
TI  - A case of estrogen dermatitis.
AB  - A 29-year-old Korean woman had erythematous papular patches on her face for six
      months. The eruptions recurred in a cyclic fashion along with her menstruation.
      The patient responded positively to an intradermal skin test for estrogen and
      showed marked improvement with the antiestrogen drug, Tamoxifen. We concluded
      that sensitivity to her own estrogen caused this dermatitis, that an intradermal
      skin test with progesterone and estrogen should be carried out routinely in
      patients with cyclic premenstrual flares, and that tamoxifen can be used as a
      specific therapy. To the best of our knowledge, this woman is the first patient
      with estrogen dermatitis reported in Korea.

PMID- 9198326
TI  - Angiosarcoma which developed on the abdominal wall: report of a case.
AB  - We report a 68-year-old Japanese woman with angiosarcoma (AS) on the abdominal
      wall. To the best of our knowledge, she is the third such patient reported from
      Japan.

PMID- 9198327
TI  - Localized myxedema associated with diabetes mellitus.

PMID- 9198328
TI  - The use of polylactic acid polymers in local drug delivery and guided tissue
      regeneration (at Nihon University School of Dentistry on November 12, 1996).

PMID- 9198329
TI  - Evolution of AIDS and AIDS related malignancies in pediatric patients in the
      United States.
AB  - The pediatric AIDS epidemic began in the U.S.A. between 1983 and 1985. Hemophilia
      patients were among the first victims of this disease with the majority of these
      patients infected prior to 1984. At the South Texas Hemophilia Center 69 of 108
      patients less than 21 years of age demonstrated serologic evidence of infection.
      Of these patients, 6 subsequently developed malignancies between 1987 and 1994.
      Between 1992 and 1996 data was subsequently accumulated on the development of
      malignancy in HIV positive patients through the Pediatric Oncology Group, which
      to date has enrolled 24 HIV positive children with malignancy. In these studies
      the majority of patients had B cell, non-Hodgkin's lymphomas, however
      approximately 20% of the patients were identified with leiomyosarcomas.
      Histologic studies of tumors of 6 children with AIDS and leiomyosarcomas or
      leiomyoma identified the EBV receptor or CD 21 in the tumor using
      immunoperoxidase techniques, whereas similar staining was not seen in smooth
      muscle tumors from HIV negative children. In situ hybridization techniques
      identified EBV-EBER probe in the tumors from HIV positive patients. In 2 patients
      with adequate tumor tissue EBV genome was present in high concentration using PCR
      techniques and Southern blot studies showed a monoclonal and biclonal
      proliferation. Other laboratories have reported similar EBV findings in lymphomas
      from AIDS patients. Thus EBV appears to be an important cofactor in development
      of malignancy in pediatric AIDS patients.

PMID- 9198330
TI  - Effects of nonopsonized Escherichia coli on myeloperoxidase activity in medium
      used for incubation of leukocytes from patients with gingivitis and
      periodontitis.
AB  - An attempt was made to explore the myeloperoxidase (MPO) activity in medium used
      for incubation of peripheral venous blood (PVB) leukocytes from patients with
      gingivitis and periodontitis and to compare it with that of periodontally healthy
      subjects. The study population included 54 gingivitis patients (G), 52
      periodontitis patients (P) and 52 control subjects (C). All these groups were
      assessed by clinical, laboratory and statistical methods. The leukocytes were
      incubated with opsonized zymosan, Escherichia coli ATCC25922, nonopsonized E.coli
      or Staphylococcus aureus 256. The respective levels of MPO activity in incubation
      media of PVB leukocytes taken from group G patients were 598.0 +/- 29.2
      conventional units (c.u.), 640.0 +/- 26.3 c.u., 662.0 +/- 37.6 c.u. and 750.0 +/-
      40.8 c.u. (control incubation medium: 564.0 +/- 25.1 c.u.); those for group P
      patients were 672.0 +/- 34.3 c.u., 678.0 +/- 43.1 c.u., 692.0 +/- 47.9 c.u. and
      762.0 +/- 34.7 c.u. (control: 612.0 +/- 35.2 c.u.); those for group C subjects
      were 556.0 +/- 30.2 c. u., 714.0 +/- 28.2 c.u., 1276.0 +/- 69.0 c.u. and 794.0 +/
      47.1 c.u. (control: 534.0 +/- 29.0 c.u.). MPO activity was increased most
      significantly when nonopsonized E.coli was added to the incubation medium of PVB
      leukocytes taken from subjects with intact periodontium. MPO activity was
      unchanged when the leukocytes were taken from periodontitis patients.

PMID- 9198331
TI  - Injury to myenteric plexus of intestinal segments after vascular pedicle
      interruption: an experimental study in rats and rabbits.
AB  - A study was conducted in rats and rabbits to histologically evaluate the effect
      of acute and late interruption of blood supply on the myenteric plexus located
      between the circular and longitudinal layers of the muscularis externa
      (Auerbach's plexus). An intestinal segment measuring 2 cm in rats and
      approximately 8cm in rabbits was sectioned and isolated on a mesenteric vascular
      pedicle. Animals in Group underwent clamping of the vascular pedicle for 1, 2, 3,
      4, 5 or 6 h. There were 5 animals in each of these subgroups. Group: Intestinal
      segments with intact vascular pedicles were transferred from the abdominal cavity
      into the subcutaneous space. Groups with 5 animals in each underwent pedicle
      ligation immediately and at 1, 2, 3 or 4 weeks after the first operation. Three
      days later, histological studies were carried out. Injury to the myenteric plexus
      and the longitudinal muscle was observed in the viable intestinal segments when
      the mesenteric vascular pedicle was clamped for 4 to 5 h. Similar findings were
      observed when the pedicle was ligated within 1 to 2 weeks after grafting. The
      present results show that ischemia can cause injury to the myenteric plexus in
      the surviving intestine.

PMID- 9198332
TI  - Skeletal and dental changes after orthognathic surgical treatment of mandibular
      prognathism.
AB  - Ten patients with skeletal and dental Class III malocclusion with mandibular
      prognathism were treated orthodontically and surgically and the effects of the
      ramus sagittal split osteotomy technique on facial morphology and the dentofacial
      complex were investigated.

PMID- 9198333
TI  - Effect of dental cyst epithelium-conditioned medium on collagenase production by
      periodontal ligament fibroblasts.
AB  - Seven dental cyst epithelia were cultured in vitro and the conditioned media were
      analyzed for periodontal ligament fibroblast collagenase production. All the cyst
      epithelium-conditioned media stimulated fibroblast collagenase production,
      indicating that dental cyst epithelium, which is considered to be identical to
      the cell rests of Malassez, might play a role in periodontal pocket formation.

PMID- 9198334
TI  - Peripheral ameloblastoma.
AB  - A case of peripheral ameloblastoma in a 57-years-old woman is presented, along
      with a discussion of the clinical and histological characteristics of the lesion.
      After clinical and radiographic examinations, and with a differential diagnosis
      of pyogenic granuloma, an excisional biopsy was performed and the material
      collected was sent for histological examination. On the basis of the
      histopathological diagnosis, a second operation was performed with a wide safety
      margin, including bone tissue, which did not show any involvement with the
      odontogenic neoplasm.

PMID- 9198335
TI  - The effect of oxidizing water on metallic restorations in the mouth: in vitro
      reduction behavior of oxidizing water.
AB  - Mouth-rinsing with oxydized water which contains electrolytically generated
      chlorine is known to hinder dental plaque formation and growth, but it also
      accelerates the deterioration of metallic restorations in the mouth. The present
      work consists of an in vitro study to elucidate the electrochemical reactions
      involved in the reduction of oxydized water on dental alloys through a systematic
      investigation of the potentiostatic polarization behavior of dental alloy
      electrodes. The five dental alloys selected for investigation were gold alloy,
      gold alloy containing platinum, silver-palladium-gold alloy, conventional amalgam
      and high copper amalgam. The corrosion potentials of all dental alloy electrodes
      were shown to be more noble in oxydized water than in 0.1N sodium chloride
      solution. The potential differences between the corrosion potentials were
      relatively small in the case of amalgam electrodes. The polarization curves for
      all of the dental alloy electrodes in oxydized water revealed reduction currents
      of chlorine, hypochlorous acid, dissolved oxygen and oxonium ion. The reduction
      of chlorine and hypochlorous acid started at a more noble potential than that of
      dissolved oxygen. The dental alloys studied, except the amalgams, did not
      dissolve excessively at the corrosion potentials in oxydized water.

PMID- 9198336
TI  - Home community cancer care: parents' perspectives.
AB  - This article reports on the results of a survey on the needs of parents of
      children with cancer and explores the needs of the parents, the parents'
      perceived importance of the needs, and whether the needs have been met. The study
      was designed to identify any differences in needs between parents whose children
      received all of their care at the major tertiary center (n = 16) and parents
      whose children received at least some of their care in their local community (n =
      40). There were no significant differences between the two groups. Parents
      reported that their important needs for information were met, but other needs
      (financial assistance, time, and rest) were unmet. Findings indicate that health
      care providers who care for families of children with cancer need to perform
      careful individual assessments throughout the treatment period.

PMID- 9198337
TI  - The Inventory of Functional Status-Caregiver of a Child in a Body Cast.
AB  - The Inventory of Functional Status-Caregiver of a Child in a Body Cast (IFSCCBC),
      which was derived from the Roy Adaptation Model, includes subscales measuring the
      extent to which parental caregivers or their surrogates continue their usual
      household, social and community, childcare, personal care, and occupational
      activities while caring for a child in a body cast. Content validity was
      established at 90%. Internal consistency reliability ranged from 0.63 to 0.88,
      using item to subscale correlations. Subscale to total IFSCCBC score correlations
      ranged from 0.14 to 0.75. Initial construct validity testing was accomplished by
      examination of subscale to subscale correlations. The IFSCCBC may be used in
      research and clinical practice to assess the functional status of parents or
      their surrogates while they are caring for a child in a body cast.

PMID- 9198338
TI  - Health promotion and injury prevention in a child development center.
AB  - The purpose of the study was to determine if a nurse-directed health promotion
      program in a day care center increased the health of the children in the center
      and decreased injury rates. The research used a quasi-experimental time series
      design to answer the research questions. The convenience sample consisted of 29
      children between the ages of 6 weeks to 5 years who were enrolled in a university
      child care center in a metropolitan area. The subjects had their health evaluated
      by a registered nurse, using the Child Health Assessment Inventory, once per week
      for 4 consecutive weeks. The Child Health Assessment Inventory measures frequent
      childhood illnesses and injuries. At the end of this first stage of data
      collection the Health Promotion Program was given to the staff members in the
      center. The program consisted of primary care information, such as signs and
      symptoms of childhood illness, infection control, injury prevention, and first
      aid. At the conclusion of the program the children had their health evaluated
      again once per week for 4 weeks. Repeated measures ANOVA showed there was a
      significant decrease in upper respiratory illness and accidental injury rates.
      The clinical application of this research is that a nurse-directed health
      promotion program can have an impact on childhood injuries. Subsequent research
      can determine if similar health promotion classes to parents and children have a
      positive effect on health.

PMID- 9198339
TI  - The influence of length of pediatric nursing experience on key cues used to
      assess infant pain.
AB  - This study examined (1) the influence of continuing education and length of
      pediatric nursing experience on infant pain assessments, (2) length of pediatric
      nursing experience on the cues used in making these assessments, and (3) the
      relationships between cues and assessed levels of pain. The convenience sample
      consisted of 20 nurses with less than 1 year of pediatric nursing experience, 20
      nurses with more than 1 year of pediatric nursing experience but less than 5
      years, and 24 nurses with more than 5 years pediatric nursing experience. All had
      at least a Bachelor of Science in Nursing degree. Participants assessed
      videotaped infants in varying degrees of pain, as determined by an expert panel.
      Results fit with, and provide some quantitative illustration for, the model of
      clinical nursing development as described by Benner and coworkers. More
      experienced nurse participants agreed more with the expert panel on levels of
      assessed pain than the other nurse participants. Similarities and differences in
      the relationship between key cues and level of assessed pain among nurse
      participants with differing lengths of pediatric nursing experience are presented
      and discussed.

PMID- 9198340
TI  - Parent stress and coping in NICU and PICU.
AB  - The purpose of this study was to identify and compare parental perceptions of
      their stress and coping experiences with children in pediatric intensive care
      units (PICU) and the neonatal intensive care units (NICU). The sample consisted
      of 31 NICU and 20 PICU parents. Parents in both units experienced the most stress
      from alteration in their parenting role and in their infants' behavior and
      appearance. Parents of children in PICU found assistance with parenting role more
      helpful than parents of children in NICU. Parents with children in the PICU
      perceived problems-focused coping more helpful than parents with children in the
      NICU; parents of children in NICU found emotion-focused coping more helpful than
      parents of children in PICU. Parents in both units considered problem-focused
      coping more helpful than appraisal- or emotion-focused coping.

PMID- 9198341
TI  - Inadequate pain management and associated morbidity in children at home after
      tonsillectomy.
AB  - A telephone interview with the parents of 84 children who underwent tonsillectomy
      was conducted within 24 hours after discharge from an ambulatory surgery center.
      Parents were asked to rate the intensity of their child's pain and data were
      collected on the type, dose, and amount of analgesics administered, and the types
      of side effects the children experienced. The mean age of the children was 7
      years (SD = 2.31), with an equal number of boys and girls. Overall mean pain
      intensity was 1.42 (SD = 0.71) and the worst pain intensity ranged from 0 to 3
      (Mean = 1.93; SD = 0.83). Acetaminophen with codeine was the most common
      analgesic prescribed and administered. Children received an average of 3 doses in
      the first 24 hours after surgery. Seventy-seven percent of the parents stated
      that pain relief from the analgesic was adequate. Of the 23% who did not feel
      that pain control was adequate, only 7% contacted a physician. The majority of
      the children experienced restless sleep (62%), behavior changes (75%), and
      difficulty taking oral fluids because of complaints of pain (56%). Twenty-six
      percent of the children had one or more episodes of emesis. Our data suggest that
      children experience a significant amount of pain in the first 24 hours after
      tonsillectomy and that parents administer analgesics less frequently than the
      drugs are prescribed. In addition, children experience significant deleterious
      effects (i.e., poor oral fluid intake, sleep disturbance, behavioral changes, and
      emesis) associated with the undertreatment of pain, the analgesic administered,
      or the surgery itself.

PMID- 9198342
TI  - Nurses' role in the prevention of teen pregnancy.

PMID- 9198343
TI  - Streamlining discharge planning for the child with a new tracheotomy.

PMID- 9198344
TI  - Childhood enuresis: application of Orem's Self-Care Practice Model to home visits
      in Turkey.

PMID- 9198345
TI  - Amputation and reamputation of the diabetic foot.
AB  - The authors compare the level of foot amputation by age, prevalence of arterial
      disease as a precipitating factor, gender, and ethnicity in persons with diabetes
      mellitus. Medical records were abstracted for each hospitalization for a lower
      extremity amputation from January 1 to December 31, 1993, in six metropolitan
      statistical areas in south Texas. Amputation level was defined by ICD-9-CM codes
      and were categorized as foot, leg, and thigh amputations. Foot-level amputations
      were further subcategorized as hallux or first ray, middle, fifth, multiple digit
      or ray, and midfoot amputations. Only the highest amputation level for each
      individual was used in the analysis. Of 1,043 subjects undergoing a lower
      extremity amputation in south Texas in the year 1993, 477 received their
      amputation at the level of the foot. African-Americans requiring a foot-level
      amputation were at significantly higher risk to undergo a midfoot-level
      amputation than was the rest of the population. Nearly 40% of all subjects
      undergoing a foot-level amputation had a previous history of amputation. However,
      nearly 40% of subjects undergoing foot amputations had not been diagnosed either
      before or during admission with peripheral arterial occlusive disease, suggesting
      a causal pathway dependent primarily on neuropathy. This implies that better
      screening of diabetic patients with appropriate risk-directed treatment at the
      primary care level may significantly impact the large number of preventable
      diabetes-related lower extremity amputations.

PMID- 9198346
TI  - The acutely infected diabetic foot is not adequately evaluated in an inpatient
      setting.
AB  - OBJECTIVE: To evaluate the standard of evaluation and treatment of the infected
      diabetic foot ulceration at a 551-bed university teaching institution. DESIGN: A
      retrospective review of a 4-year consecutive sample (1991-1994). POPULATION: Two
      hundred fifty-five patients who were admitted to a hospital for care of an
      infected diabetic foot ulceration. Patients were subdivided into the following 4
      dichotomous variables: (1) whether the patient underwent a lower-extremity
      amputation, (2) whether the patient was admitted once or multiple times, (3)
      whether the patient underwent intraoperative debridement, and (4) whether the
      patient was admitted to medical or surgical services. RESULTS: All groups that
      were evaluated had undergone a less than adequate foot examination. Of the
      admitted patients, 31.4% did not have their pedal pulses documented; 59.7% of the
      admitted patients were not evaluated for the presence or absence of protective
      sensation. Nearly 90% of the wounds were not evaluated for involvement of
      underlying structures, and foot radiographs were not performed in 32.9% of the
      patients. There were more blood cultures ordered (62.0%) than wound cultures
      (51.4%). CONCLUSION: The results of this study highlight the need for a
      systematic, detailed lower-extremity examination for every diabetic patient who
      is admitted to a hospital, particularly those who are admitted with a primary
      diagnosis that involves a foot complication.

PMID- 9198347
TI  - Novel methodology to obtain salient biomechanical characteristics of insole
      materials.
AB  - Viscoelastic inserts are commonly used as artificial shock absorbers to prevent
      neuropathic foot ulcerations by decreasing pressure on the sole of the foot.
      Unfortunately, there is little scientific information available to guide
      physicians in the selection of appropriate insole materials. Therefore, a novel
      methodology was developed to form a rational platform for biomechanical
      characterizations of insole material durability, which consisted of in vivo gait
      analysis and in vitro bioengineering measurements. Results show significant
      differences in the compressive stiffness of the tested insoles and the rate of
      change over time in both compressive stiffness and peak pressures measured. Good
      correlations were found between pressure-time integral and Young's modulus (r2 =
      0.93), and total energy applied and Young's modulus (r2 = 0.87).

PMID- 9198349
TI  - Hyperbaric oxygen therapy and the diabetic foot.
AB  - Hyperbaric oxygen therapy is an adjunctive wound-healing modality receiving
      increasing use for problem wounds, particularly diabetic foot wounds.
      Nevertheless, few clinicians understand the physiologic basis for this modality;
      how patients are selected, or the expected results. The author reviews the
      development of hyperbaric oxygen therapy, selection of patients, and clinical
      studies of this modality for diabetic patients with foot wounds.

PMID- 9198348
TI  - The natural history of acute Charcot's arthropathy in a diabetic foot specialty
      clinic.
AB  - The aim of this longitudinal study was to report on the clinical characteristics
      and treatment course of acute Charcot's arthropathy at a tertiary care diabetic
      foot clinic. Fifty-five diabetic subjects, with a mean age of 58.6 +/- 8.5 years,
      were studied. All patients were treated with serial total contact casting until
      quiescence. Following casting and before transfer to prescription footwear,
      patients were eased into unprotected weightbearing via a removable cast walker.
      This cohort was followed for their entire treatment course and for a mean 92.6 +/
      33.7 weeks following return to shoes. Pain was the most frequent presenting
      complaint in these otherwise insensate patients (76%). The mean duration of
      casting was 18.5 +/- 10.6 weeks. Patients returned to footwear in a mean 28.3 +/-
      14.5 weeks. Nine per cent of the population had bilateral arthropathy. These
      subjects were casted significantly longer than the unilateral group (p < 0.02).
      Surgery was performed on 25% of patients, with approximately two-thirds of these
      procedures involving plantar exostectomies and one-third fusions of affected
      joints. Patients receiving surgery remained casted significantly longer than non
      surgical patients (p < 0.05). Additionally, men were casted longer than women (p
      < 0.008). Acute Charcot's arthropathy requires prompt, uncompromising reduction
      in weightbearing stress. Our data show that the ambulatory total contact cast is
      very effective for this. Regardless of the specific treatment method instituted,
      it is imperative that appropriate and aggressive treatment be undertaken
      immediately following diagnosis to help prevent progression to a profoundly
      debilitating, limb-threatening deformity.

PMID- 9198350
TI  - Diabetic foot update 1996.

PMID- 9198352
TI  - Advances in the management of urinary incontinence in children.

PMID- 9198353
TI  - Results of a search for missed cases of reportable communicable diseases using
      hospital discharge data.
AB  - To assess how reliably hospitals report serious, uncommon communicable diseases
      to the Department for Public Health, we searched the 1995 hospital discharge data
      set (HDDS) collected by the Kentucky Health Policy Board for cases of 11
      diseases. Of 17 case records found, 4 represented disease occurrences that had
      been reported to the Department; 6 represented coding errors in the HDDS; 4 were
      instances where a reportable disease had been suspected but not confirmed by
      subsequent workup; 1 case was a resident of another state; and 2 were cases of
      invasive Hemophilus influenzae infection in adults that should have been reported
      to the Department. The study found no evidence that hospitals failed to report
      vaccine-preventable diseases. There was evidence that the HDDS needs improved
      accuracy to maximize its usefulness for public health purposes.

PMID- 9198354
TI  - Manifestations of relapsing Epstein-Barr virus illness.
AB  - The Epstein-Barr Virus is well known for its pattern of communicability and
      features of clinical disease. It is a member of the herpes virus family and may
      establish a latency state in infected individuals. Characteristics of latency and
      reactivation have been well defined for both herpes and varicella. The Epstein
      Barr Virus has been shown to establish a latency state within B lymphocytes,
      salivary gland epithelium, and oropharyngeal epithelial cells. Reactivation of
      the virus from these sites could produce relapse of EBV illness. Characteristics
      of relapse are described in this report.

PMID- 9198355
TI  - A daily devotional.

PMID- 9198356
TI  - Everyday murder.

PMID- 9198357
TI  - A problem of optimal harvesting policy in two-stage age-dependent populations.
AB  - The optimal equilibrium harvesting policy is investigated for an age-dependent
      population of females whose life history consists of two stages termed eggs (or
      juveniles) and adults. Using a continuous-time linear model, we consider
      admissible harvesting policies in which a certain fraction of individuals of
      fixed ages is harvested per unit time in both stages to bring the population to
      an equilibrium level. Determination of the harvest rate that maximizes the
      sustainable yield, subject to a linear ecological or economic constraint, leads
      to a nonlinear, nonconvex optimization problem. The optimal policy is shown to
      consist of harvesting at most three ages. Thus, we say that the harvest is
      trimodal. In one stage, at most two ages are harvested, with the oldest being
      harvested completely; in the other, at most one age is harvested completely. In
      each stage, the age totally removed, if present, is older than the surplus age,
      which is the age at which the proportion of the expected number of eggs
      multiplied by the proportion of the expected number of adults first exceeds one.
      The three harvesting ages are dependent on the birth, maturation, and death rates
      and on the economic parameters of the problem. A simple algorithm to find the
      optimum harvesting strategy is described.

PMID- 9198358
TI  - Modeling the impact of HIV on the spread of tuberculosis in the United States.
AB  - Tuberculosis (TB) was thought to be safely in decline in the United States in the
      mid-1980s because the number of cases had dropped by 74% between 1953 and 1985.
      An increase in TB cases was reported, however, in 1986, and an upward trend in TB
      incidence has continued. The turnaround in TB is well correlated with the rise of
      the HIV (human immunodeficiency virus) epidemic. The purpose of this work is to
      investigate, through the use of mathematical models, the magnitude and duration
      of the effect that the HIV epidemic may have on TB. Models are developed which
      reflect the transmission dynamics of both TB and HIV, and the relative merits of
      these models are discussed. The models are then linked together to form a model
      for the combined spread of both diseases. A numerical study is performed to
      investigate the influence of certain key parameters. The effect that HIV will
      have on the general population is found to be dependent on the contact structure
      between the general population and the HIV risk groups, as well as a possible
      shift in the dynamics associated with TB transmission.

PMID- 9198359
TI  - [Protective effect of onpi-to (TJ-8117) on the expression of apoptosis in 5/6
      nephrectomized rats].
AB  - The present study was designed to clarify the effects of TJ-8117 on apoptosis in
      the glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/day), captopril (50
      mg/kg/day) and nicardipine (50 mg/kg/day) were administered as drinking water
      from the 56th day after renal ablation, and continued throughout the experiment.
      All rats were sacrificed at 13 weeks and renal tissues were removed to quantify
      histopathological and apoptotic parameters in glomeruli. TJ-8117 inhibited
      proteinuria, matrix index and decrease in the number of total cells in glomeruli
      of nephrectomized rats. In addition, the increase in apoptotic body and DNA
      fragmentation was significantly inhibited in the TJ-8117-treated group. Captopril
      and nicardipine failed to inhibit both parameters. In 400 mg/kg of the TJ-8117
      treated group, the number of Bcl -2 positive cells in the glomeruli was elevated
      compared with the 5/6 nephrectomized control group. In addition, the number of
      Bax positive cells in the TJ-8117 group was significantly suppressed in a dose
      dependent manner. These results suggest that TJ-8117 may inhibit apoptosis in the
      late stage of this model by suppressing matrix accumulation and progression of
      glomerulosclerosis. The apoptosis-preventing effect may be mediated by decreased
      expression of Bax in the glomerular cells.

PMID- 9198360
TI  - [Renal lesions of rats induced by antibodies to cultured rat glomerular
      epithelial cells and mesangial cells].
AB  - Renal lesions of rats induced by antibodies to cultured rat glomerular epithelial
      cells (GEC) and mesangial cells (GMC) were studied. Antibodies to cultured rat
      GEC and GMC were produced by immunization of rabbits with GEC and GMC
      respectively. The rats injected with anti-GEC antibody showed a small amount of
      urinary protein, glomerular deposition of rabbit IgG and subepithelial dense
      deposits observed by electron microscopy. Proteinuria was suppressed in the rats
      in which complement was depleted with cobra venom factor. Western blot analysis
      demonstrated a band of 200 KD in GEC lysates reacted with anti-GEC antibody. The
      rats injected with anti-GMC antibody showed little urinary protein, glomerular
      deposition of rabbit IgG and mesangial dense deposits. Western blot analysis
      demonstrated two bands of 43 and 14 KD in GMC lysates reacted with anti-GMC
      antibody. These data showed that the injection of anti-GEC antibody or anti-GMC
      antibody induced similar lesions to passive Heymann nephritis and anti Thy 1.1
      nephritis. This study suggested that antigenicity of structural glomerular cells
      is important as the antigens of glomerulonephritis.

PMID- 9198361
TI  - [The role of nitric oxide in two-kidney, one-clip renovascular hypertensive
      rats].
AB  - The relationship between blood pressure(BP) and nitric oxide(NO) in two-kidney,
      one-clip renovascular hypertensive rats (2K1C) was investigated. Although urinary
      NO2- + NO3-(NOx) excretion (UNOX V) increased 2 weeks after surgery (2W-2K1C),
      UNOX V decreased 4 weeks after surgery (4W-2K1C) compared with that of the
      control. UNOX V levels were restored 2 weeks after unclipping (U2K1C). BP and
      UNOX V did not change in 2K1C after treatment with L-arginine (Arg-2K1C). Aorta
      from 4W-2K1C and Arg-2K1C showed significantly decreased relaxation responses to
      acetylcholine(Ach), but Ach-induced relaxation of aorta in U2K1C returned to
      control-level responses. De-endothelialized aorta from 4W-2K1C, Arg-2K1C, and
      U2K1C had significantly decreased relaxation responses to lipopolysaccharide.
      These data suggest that: (1) transient increase of NO synthesis is accompanied by
      elevation of BP, but long-term elevation of BP decreases NO synthesis in
      endothelium and smooth muscle cells: (2) L-arginine supplement has no effect on
      the development of hypertension and on NO production by endothelium and smooth
      muscle cells in 2K1C.

PMID- 9198362
TI  - [Effects of cyclosporin A on the diurnal variation of blood pressure in patients
      with nephrotic syndrome].
AB  - We investigated the hemodynamic, renal, and hormonal effects of cyclosporin A
      (CyA) treatment (6 mg/kg per day) for 4 weeks in 12 patients with nephrotic
      syndrome (8 women: 4 men, aged 36-66 years, 3 cases of focal glomerular
      sclerosis: 9 cases of membranous nephropathy). To evaluate the effects of CyA on
      the diurnal variation of blood pressure (BP), 24-h non-invasive BP monitoring was
      performed using model ABPM-630 (Nihon Colin, Tokyo, Japan) before and during CyA
      treatment. As indices of hemodynamics, intra-arterial pressure was monitored and
      cardiac output was measured by the dye-dilution technique using a cuvette at 0
      and 4 weeks after treatment. CyA ameliorated urinary protein excretion and
      hypoproteinemia from 3.5 +/- 0.9 to 2.2 +/- 0.7 g/day, and serum protein
      concentration from 4.9 +/- 0.2 to 5.5 +/- 0.2 g/dl after 4 weeks' treatment.
      Endogenous creatinine clearance, 24-h urinary sodium excretion, and plasma renin
      activity decreased significantly at 1 week. CyA treatment raised casual BP from
      122 +/- 4/75 +/- 2 to 140 +/- 5/87 +/- 3 mmHg after 1 week and to 146 +/- 4/90 +/
      2 mmHg after 4 weeks. Before treatment 24-h ambulatory BP monitoring showed BP
      reduction at night (116 +/- 5/68 +/- 3 mmHg) compared to the daytime (124 +/-
      5/75 +/- 2 mmHg). The diurnal variation of BP disappeared during CyA treatment;
      mean daytime and nighttime pressures were 135 +/- 4/81 +/- 2, 132 +/- 5/80 +/- 3
      mmHg at 1 week and 139 +/- 5/83 +/- 3, 131 +/- 6/80 +/- 3 mmHg at 4 weeks,
      respectively. On hemodynamic study; a 4-week treatment with CyA increased mean
      arterial pressure from 91 +/- 3 to 104 +/- 3 mmHg, total peripheral resistance
      index from 2.1 +/- 0.1 to 2.5 +/- 0.1 x 10(3) dyne.sec.cm-5.m2, and unchanged
      heart rate and cardiac index. Serum Mg concentration decreased from 2.1 +/- 0.1
      to 1.7 +/- 0.1 mg/dl. These results suggest that CyA-induced hypertension is
      characterized by the loss of nocturnal decline in blood pressure, which is
      accompanied by volume retention after 1 week and systemic vasoconstriction after
      4 weeks.

PMID- 9198363
TI  - [Type III procollagen N-peptide and hyaluronate in serum and dialysate of CAPD
      patients].
AB  - Long-term CAPD may develop peritoneal fibrosis, which is thought to be related to
      permanent loss of ultrafiltration capacity and sclerosing peritonitis. In CAPD
      patients, we examined the serum (P-) and effluent (D-) levels of type III
      procollagen N-peptide (P III P) and hyaluronate (HA), which are expected to
      change concomitantly with a local increase in submesothelial extracellular matrix
      of the peritoneum. We selected 40 CAPD patients (age: 46.3 +/- 11.3 years, time
      on CAPD: 33.6 +/- 26.2 months), who were not suffering from chronic liver
      disease, any inflammatory disease, nor peritonitis during the previous month. P-P
      III P, P-HA, D-P III P, and D-HA were measured by PET (values after 4-hour
      dwelling). D/P ratios (P III P 0.330 +/- 0.137, HA 5.68 +/- 6.44) suggested that
      their source was from the peritoneum. Although neither P-P III P nor log P-HA
      value had a significant correlation with age nor time on CAPD, both had
      significantly positive correlations (p = 0.0009, 0.0005, respectively) with time
      on total dialysis (including hemodialysis). D-P III P did not have a significant
      correlation with age nor time on total dialysis but had a significantly positive
      correlation (p = 0.0098) with D/P-creatinine. Although log D-HA had significantly
      positive correlations with time on CAPD and time on total dialysis (p = 0.0007,
      0.0051, respectively), time on CAPD was first entered (F = 16.5) and time on
      total dialysis was removed (F to enter: 4) by stepwise regression analysis. In
      conclusion, a local increase in extracellular matrix of the peritoneum in CAPD
      patients, indicated by increases in P III P and HA in the effluent, may be
      related to higher peritoneal permeability and a longer duration of PD.

PMID- 9198364
TI  - [A case of nephrotic syndrome after bone marrow transplantation].
AB  - We reported a 27-year-old man who developed nephrotic syndrome 12 months after a
      bone marrow transplantation from his HLA-identical sister for chronic myelocytic
      leukemia. Anti-nuclear antibodies had been serially investigated after the bone
      marrow transplantation. They were detected in his serum 5 months before the
      appearance of proteinuria, but he tested negative at the onset of nephrotic
      syndrome. Histological analysis of the renal biopsy revealed subepithelial and
      subendothelial immune deposits in the glomerular basement membrane with increased
      mesangial matrix and cells. These findings suggested immune complex
      glomerulonephritis due to chronic graft-versus-host disease (GVHD) after bone
      marrow transplantation. In murine experimental chronic GVHD, anti-nuclear
      antibodies, which generate immune complexes that deposit or form in the kidney
      have been detected.

PMID- 9198365
TI  - [A case of necrotizing crescentic glomerulonephritis with arteritis due to
      secondary amyloidosis following rheumatoid arthritis].
AB  - A 47-year-old woman was admitted on August 4th, 1995, because of edema of the
      lower extremities. She had been suffering from RA for about 20 years and
      underwent total knee-replacements 5 years previously. On admission, nephrotic
      syndrome and rapidly progressive glomerulonephritis had developed in association
      with ileus, melena, diarrhea, dyspnea and hemoptysis. She showed a high titer of
      serum rheumatoid factor (357.0 IU/ml) and amyloid A protein (83.9 micrograms/ml)
      with positive antinuclear antibodies (homogeneous and speckled patterns).
      However, anti-neutrophil cytoplasmic autoantibody (ELISA), immune complexes and
      anti-glomerular basement membrane antibody (ELISA) were negative. Renal biopsy
      showed microscopic PN overlapping A-type positive amyloidosis. Although the
      maintenance of hemodialysis was necessary, aggressive immunosuppressive therapy
      with steroid pulse therapy and frequent plasma exchange provided a rapid
      improvement of systemic symptoms possibly due to vasculitis. We suggested that in
      this case, massive necrotizing crescentic glomerulonephritis with systemic
      arteritis developed on the basis of secondary amyloidosis due to rheumatoid
      arthritis. In such a case, even if various serum autoantibodies and immune
      complexes were negative, plasma exchange was suggested to be effective to remove
      not only pathogenic autoantibodies but also various serum inflammatory cytokines
      which may be related with severe vasculitis and glomerulitis, in addition to
      aggressive steroid therapy which may suppress the invasion of inflammatory cells
      producing these cytokines.

PMID- 9198366
TI  - [Focal segmental glomerulosclerosis presenting nephrotic syndrome and acute renal
      failure in a patient with rheumatoid arthritis].
AB  - A 45-year-old woman with rheumatoid arthritis(RA) who developed nephrotic
      syndrome and acute renal failure was reported. She first noticed polyarthritis in
      June 1990, and was diagnosed as RA. Since her RA was not controlled with
      nonsteroidal anti-inflammatory drugs (NSAID), she started taking prednisolone 10
      mg daily and received 100 mg of D-penicillamine from October 1990 with
      improvement of the RA. In March 1991, she noticed edema of the face and legs, at
      which time massive proteinuria and hematuria were first noted. Because of her
      nephrosis, she was referred to our hospital for further evaluation. Laboratory
      investigations revealed 24-hour urine proteinuria of 37 g, serum creatinine, 2.7
      mg/dl, blood urea nitrogen, 43.5 mg/dl, total protein, 4.1 g/dl, albumin, 1.5
      mg/dl, and total cholesterol, 600 mg/dl. The rheumatoid factor and anti-nuclear
      antibody were positive. Renal biopsy showed focal segmental glomerulosclerosis
      (FSGS). Her nephrotic syndrome and renal dysfunction recovered after the
      administration of prednisolone at 60 mg/day. The possible pathogenesis of FSGS in
      patients with RA was discussed.

PMID- 9198367
TI  - [A case of primary antiphospholipid antibody syndrome with severe nephrotic
      syndrome showing remarkable endothelial cell damage in the capillary lumen].
AB  - A 25-year-old woman complained of anasarca and was admitted to Sakura National
      hospital on the presumptive diagnosis of nephrotic syndrome with 10.7 g of 24
      hour urinary protein. At first, lupus nephritis with antiphospholipid antibody
      syndrome was suspected because of prolongation of APTT, existence of lupus
      anticoagulant and elevation of serum anticardiolipin antibody titer (IgM) in
      addition to positive ANA, lymphocytopenia and the biologically false positive
      test for syphilis (BFPTS). On day 28 of hospitalization, renal biopsy findings
      revealed severe endocapillary cell damage, such as swelling and proliferation of
      endothelial cells, fragmentation and double contour of the basement membrane
      walls, which were located only in the capillary lumens with a few thrombi.
      Immunofluorescent micrography revealed the absence of specific immunoglobulin or
      complement deposit. Therefore, the diagnosis of lupus nephritis was negated as
      these findings were suggestive of characteristic glomerulopathy due to primary
      antiphospholipid antibody syndrome. She was treated initially with oral
      prednisolone 60 mg and intravenous infusion of heparin 20,000 units daily.
      Moreover, cyclophosphamide 750 mg was administered intravenously as pulse therapy
      on day 13 as her serum level of CH50 had fallen suddenly, and hemodialysis was
      necessary because her renal function had deteriorated and she was suffering from
      cough and orthopnea with overhydratin. After the combined therapy, BFPTS
      disappeared and APTT returned to the normal range: dialysis treatment was not
      required further after the 4th hemodialysis. Thereafter, renal function improved
      and complete remission of nephrotic syndrome was obtained. This patient was a
      case of primary antiphospholipid antibody syndrome in which endothelial cell
      damage was located exclusively in the capillary lumens and pulse cyclophosphamide
      therapy in addition to prednisolone and anticoagulant was effective. We present
      this instructive case to promote understanding of the pathogenesis of primary
      antiphospholipid antibody syndrome.

PMID- 9198368
TI  - [Chinese herbs nephropathy in the Kansai area: a warning report].
AB  - In 1993, Vanherweghem and his associates reported cases of rapidly progressive
      renal interstitial fibrosis in young women who were administered a slimming
      regimen including Chinese herbs. Subsequently, similar cases have been reported.
      In Japan, especially in the Kansai area, several cases of Chinese herbs
      nephropathy have already been reported. We experienced a patient suffering from
      Chinese herbs nephropathy (CHN), and further detected aristolochic acids from the
      Chinese herbs taken by the patient. Aristolochic acids are known to be causative
      agents of CHN. The danger of CHN should be noted as soon as possible and drugs
      containing aristolochic acids should be prohibited.

PMID- 9198369
TI  - Bone metabolism and daily physical activity in women undergoing hemodialysis.
AB  - BACKGROUND: We investigated the relationships between bone mineral density (BMD)
      and bone metabolic markers in 41 Japanese women (age range, 23 to 85 years; mean,
      61; SD, 16) undergoing hemodialysis, and the relationship between BMD and daily
      physical activity with nutritional state in those patients. METHOD: The patients
      were divided into a group with hyperparathyroidism (intact parathyroid hormone
      [PTH] > or = 300 pg/mL, n = 9) and a group without hyperparathyroidism (intact
      PTH < 300 pg/mL, n = 32). Total BMD and spinal BMD (regional evaluation) were
      measured using dual-energy X-ray absorptiometry. We determined serum
      concentrations of intact PTH, osteocalcin (bone Gla protein) and alkaline
      phosphatase as markers of bone formation, and serum tartrate-resistant acid
      phosphatase (TRAP) as a marker of bone resorption. Mean energy expenditure per
      day was measured by calorie counters worn by the patients, and serum levels of
      total protein, albumin, cholesterol, ferritin, and blood urea nitrogen were
      measured as indices of nutritional status. RESULTS: In the group without
      hyperparathyroidism, 9 patients had a spinal BMD < 0.85 g/cm2 and were considered
      to be at risk for bone fracture. In this group, a significant correlation was
      observed between total BMD and TRAP (r = -0.52, p = 0.004). Age, duration of
      hemodialysis, dry body weight, energy expenditure per day, and serum total
      protein levels were correlated with total BMD and spinal BMD, using multiple
      regression analysis (p < 0.0001). CONCLUSIONS: In patients with low BMD, the bone
      turnover tended toward bone resorption rather than formation, without strong
      influence by parathyroid function. Energy expenditure showed a strong
      relationship to the total BMD (r = 0.32, F = 18.5), which appeared to improve
      bone turnover.

PMID- 9198370
TI  - Validation of the MCMI-III PTSD scale among combat veterans.
AB  - The new MCMI-III Posttraumatic Stress Disorder (PTSD) scale was validated on 104
      combat veterans who were divided into two groups, PTSD Treatment Group and Non
      PTSD Treatment Group. PTSD status was carefully determined by clinical interview
      and therapists' reports. The Combat Exposure Scale, the Mississippi Scale for
      Combat-related PTSD, and the Impact of Events Scale were also given. Analysis
      showed that the MCMI-III PTSD scale had a low internal consistency, but that it
      significantly differentiated the two groups and significantly correlated to those
      on other PTSD self-report scales. This scale appeared to be influenced by an
      acquiescent response style. Further validation studies are needed.

PMID- 9198371
TI  - Depression and anxiety in young children of substance abusers.
AB  - 144 5- to 13-yr.-old children of substance abusers, enrolled in an expressive
      arts therapy program, were tested for depression on the Children's Depression
      Inventory and for anxiety on the Revised Children's Manifest Anxiety Scale prior
      to treatment. Total scores for anxiety were significantly higher for girls than
      for boys; however, total depression scores did not differ between boys and girls.
      Analysis of subscale scores on each of the tests indicated several sex
      differences. Age was positively correlated with certain symptoms of depression
      for boys but not for girls. Conversely, age was negatively correlated with
      certain symptoms of anxiety for boys but not for girls. When compared to known
      norms for these assessments, girls scored significantly higher on total
      Depression but not differently than normals on total Anxiety. Boys, however,
      scored significantly lower on total Anxiety but did not score differently than
      normals on total Depression. We interpreted these findings as indicating that
      young children of substance abusers may be at risk for certain symptoms of
      anxiety and depression following their parents' addiction. Also, these symptoms
      may be manifest differently by boys and girls of various ages.

PMID- 9198372
TI  - Clinical description of children's anxiety during the Gulf War.
AB  - Interviews were carried out with 322 children, ages 5 to 16 years, to examine the
      association of war experience and their anxiety. Body language was used as
      indicator of anxiety. Girls showed significantly more discrete body movements
      than boys.

PMID- 9198373
TI  - Relationships between Schill's Self-defeating Personality Scale and Coolidge's
      Personality Disorders Inventory.
AB  - 81 men and 82 women were administered Schill's (1990) Self-defeating Personality
      Scale and Coolidge's (1992) Axis Two Inventory. As expected, Schill's and
      Coolidge's measures of self-defeating personality disorder were highly correlated
      (.70 for men and .74 for women). Scores on Schill's scale also had correlations >
      .50 with scores on six of the other personality disorder scales for men and five
      for women. This argues against self-defeating personality disorder as measured by
      Schill's scale being a distinct construct. The pattern of the correlations
      suggests that besides assessing a person's maladaptive self-defeating traits,
      Schill's measure also may assess the person's anxiety and concerns about
      interpersonal relationships.

PMID- 9198374
TI  - Characteristics and motives of adolescent volunteers in wildlife education.
AB  - The characteristics and motives of 63 suburban adolescents (20 boys, 43 girls)
      who are concerned with learning how to care for and make significant
      contributions to wildlife and the environment were assessed by telephone
      interviews. The data confirm studies of adults in that significantly more girls
      than boys became volunteers, significantly more volunteers' families than average
      families experienced caring interactions with animal life through pet ownership,
      and significantly more volunteers reported that concern for wildlife arose during
      early childhood rather than later. The data also indicate that early childhood
      experiences with pets, with adults acting as role models and providing social
      approval, and having instruction in wildlife care with peers all contributed to
      their positive attitudes toward wildlife and the pursuit of their volunteer work.
      Over-all, the results suggest that adolescents, wildlife, and the environment
      might benefit if wildlife care programs could be established for other youth such
      as inner city teenagers.

PMID- 9198375
TI  - Failure to support a test for penis envy.
AB  - Johnson (1966) reported that significantly more women than men did not comply
      with the request to return their special machine-scoring pencils after completing
      a final examination in introductory psychology. In the present replication,
      Johnson's conclusion that keeping the pencils may be manifestation of penis envy
      was not supported.

PMID- 9198376
TI  - Personality and happiness.

PMID- 9198377
TI  - K-TEA Mathematics scores of learning disabled students in resource and inclusive
      settings.
AB  - The relative effectiveness of mathematics instruction in resource rooms versus
      inclusive settings was examined with 30 boys in Grades 5 and 6 identified as
      learning disabled in mathematics. The boys were presented at the beginning of the
      school year and posttested at the end. Treatment was 45 min. of daily instruction
      in mathematics provided by six teachers for one school year. K-TEA Mathematics
      Computation and Application scores, separately compared in 2 x 2 repeated
      measures analyses of variance, were not significantly different; however, a
      significant gain was noted across settings for K-TEA Mathematics Application
      scores.

PMID- 9198378
TI  - Heart rate and heart-rate variability in patients with acute coronary heart
      disease classified on Bortner's scale as type A and type B.
AB  - We investigated heart rate and heart-rate variability in 82 patients, 60 men and
      22 women (M = 54 yr., SD = 9) with acute coronary heart disease and scores on
      Bortner's scale at hospital admission and discharge. 48 patients were classified
      by their scores on Bortner's scale as Type A and 34 as Type B. Patients with
      acute coronary heart disease classified as Type A had a significantly lower mean
      heart rate than patients with acute coronary heart disease classified as Type B
      during the day at hospital admission and discharge and during the night at
      hospital discharge. Mean heart-rate variability was also significantly higher in
      the patients with acute coronary heart disease classified as Type A than in the
      patients with acute coronary heart disease classified as Type B during the day at
      hospital admission and discharge. The differences between two groups on the
      average heart rate and heart-rate variability were not significant during the
      night at hospital admission. In our study the patients with acute coronary heart
      disease classified by scores on Bortner's scale as Type A had higher vagal tone
      and more favorable sympathovagal balance than patients classified as Type B. This
      finding may have implications for the treatment of patients with acute coronary
      heart disease and may suggest some explanation about the protective effect of
      Type A behavior also.

PMID- 9198379
TI  - Interaction of posttraumatic stress disorder and major depressive disorder among
      older combat veterans.
AB  - This study investigated the interaction of PTSD and major depressive disorder
      with common aging-related variables for a community sample of older World War II
      and Korean War veterans. Older veterans (N = 139) were divided into PTSD and
      depressed groups on the basis of interviewers' measures and compared on overall
      adjustment, social support, and health status. Only PTSD affected adjustment and
      health status.

PMID- 9198380
TI  - Is alexithymia a culture-bound construct? Validity and reliability of the
      Japanese versions of the 20-item Toronto Alexithymia Scale and modified Beth
      Israel Hospital Psychosomatic Questionnaire.
AB  - The possibility remains that alexithymia is a culture-bound construct. The
      authors examined the validity and reliability of the Japanese versions of the 20
      item Toronto Alexithymia Scale and the modified Beth Israel Hospital
      Psychosomatic Questionnaire, testing two samples of 473 college students and 149
      psychiatric outpatients. The face validity and internal consistencies were
      suggested by factor analysis, adequate internal consistency, relatively high test
      retest correlations, and high specificity and sensitivity. The Japanese versions
      of these two alexithymia scales therefore seem suitable for use among college
      students and psychiatric outpatients. However, there were several problematic
      points which may be associated with cultural differences.

PMID- 9198381
TI  - Women with high risk for breast cancer: psychological symptoms.
AB  - This pilot study compared the psychological distress of 16 women with family
      histories of breast cancer (mother, sister, daughter, aunt) and 37 women with no
      such histories, all of whom were undergoing a regular checkup in a breast health
      clinic in northern Israel. Analysis indicated that women at high risk for breast
      cancer with a suspected syndrome experienced greater psychological distress than
      the women with no such histories.

PMID- 9198382
TI  - Attitude toward medication and perceived competence among chronically psychotic
      patients.
AB  - 19 chronically psychotic outpatients who had consistently expressed doubt about
      their need for psychotropic medication provided significantly more inflated
      estimates of their performance on a problem-solving task than 18 subjects who had
      not expressed such skepticism. The findings are consistent with the view that the
      observed relationship between denial of deficits and noncompliance with treatment
      among psychotic individuals is a function of a broader pattern of self-deception.

PMID- 9198383
TI  - Motivational and behavioral correlates of life satisfaction in an elderly sample.
AB  - This study examined the relationship between self-reported life satisfaction of
      elderly persons and their motivation for competence as assessed on self-ratings
      and indirect measures of needs for achievement and affiliation. Behavioral data
      relating to frequency of engaging in mastery-type activities, social interactions
      and exercise were also gathered. This sample described themselves as content with
      their lives and healthy relative to normative levels. As predicted, there was a
      marked discrepancy between self-report and implicit measures of motivation, with
      self-reported motives being significantly correlated with satisfaction (i.e., r =
      .33 for Achievement and r = .30 for Affiliation) and implicit motives not
      significantly correlated with satisfaction. Needs for achievement and affiliation
      on the whole did not significantly correlate with actual life circumstances. The
      results suggest that competence motivation may play a small part in the
      contentment which older individuals feel in their lives.

PMID- 9198385
TI  - Black south African adolescents' attitudes about studying.
AB  - Black South African high school students (N = 523) were questioned about their
      attitudes and motivation towards studying. Analysis indicated that the students
      expressed negative attitudes toward studying and were concerned about failing.
      34% indicated a lack of interest in most school subject matter.

PMID- 9198384
TI  - An interim report on the development of the Psychological Trauma and Resources
      Scales.
AB  - The William S. Hall Psychiatric Institute Psychological Trauma and Psychological
      Resources Scales is a preliminary measure for the assessment of psychological
      trauma and psychological health from a developmental perspective. This three-part
      article (1) discusses the various rationales leading to the development of the
      scales, (2) provides a factor-analysis of responses of 336 college students, and
      (3) addresses current (N = 37) and planned efforts to establish reliability and
      validity of a more refined version.

PMID- 9198386
TI  - Age differences in WISC-III subtests of children experiencing academic
      difficulties.
AB  - WISC-III subtest scores of 180 children referred because of academic difficulties
      were analyzed for differences based on age (M = 9.6, SD = 2.7) and IQ. Rank
      orders of all subtests indicated no significant correlations across the six age
      IQ groups, suggesting that interpretation of changes in subtest rankings may
      require consideration of age and IQ, especially for such children. When data were
      organized into Acquired Knowledge, Spatial Ability, and speed-related task
      categories, analyses of variance showed a main effect for IQ. Furthermore, scores
      on Acquired Knowledge were associated with age at the lower category of IQ,
      whereas Spatial Ability and speed-related tasks were not related to age.

PMID- 9198388
TI  - Psychology of computer use: XLVII. Parameters of Internet use, abuse and
      addiction: the first 90 days of the Internet Usage Survey.
AB  - While the addictive potential of Internet usage is a topic that has attracted a
      great deal of attention, as yet little research has addressed this topic.
      Preliminary data from the Internet Usage Survey shows that most of the 563 users
      reported instances of Internet use interfering with other aspects of their lives,
      most commonly problems with managing time. A subgroup of users endorsed multiple
      usage-related problems, including several similar to those found in addictions.
      Younger users tended to have experienced more problems.

PMID- 9198387
TI  - Personality disorders in psoriasis.
AB  - Rubino and Zanna (5) have responded to our comments (1) on their report (4) on
      the association of personality disorders with psoriasis and have presented data
      comparing the personality characteristics of psoriasis patients with those in
      urticaria patients. The problems that remain with their methodology are that
      dental controls may not be equivalent to dermatologic conditions, and in the
      urticaria study, no data on premorbid functioning were provided to differentiate
      state vs trait phenomena, and they did not control for duration of illness.

PMID- 9198389
TI  - Psychometric properties of the Interpersonal Relationship Inventory with a
      homeless sample.
AB  - This paper examined the psychometric properties of the Interpersonal Relationship
      Inventory with a sample of homeless men who were first-time shelter users. The
      measure, based on social exchange theory and equity theory, has two subscales,
      one for support and the other for conflict. As yet, few measurements have been
      developed to assess conflict from within social networks. As part of a larger
      longitudinal study a sample of 166 first-time shelter users was administered the
      inventory. A student sample also filled out the inventory for comparison
      purposes. Internal consistency for both subscales was good, .90 for Support and
      .83 for Conflict. Weak interitem correlations were prevalent among many items in
      the Conflict subscale. A nearly zero correlation was found between scores on the
      Support and Conflict subscales, suggesting independence. An exploratory factor
      analysis using varimax rotation confirmed a dual factor structure. Analyses of
      variance and Scheffe contrast tests detected no statistically significant
      differences between age groups on either the Support or the Conflict subscales. A
      multiple regression analysis indicated that, when controlling for age, scores on
      the Support scale discriminated the homeless and student samples, while scores on
      the Conflict subscale do not. The Support subscale indicates excellent
      psychometric qualities, while the Conflict subscale should be refined.

PMID- 9198390
TI  - Satisfaction and trust in intimate relationships do lesbians and heterosexual
      women differ?
AB  - Although satisfaction and trust have received considerable attention in the
      literature on heterosexual relationships, little is known about lesbian
      relationships. Because females are socialized differently and acquire a different
      sexual script than males do, we predicted that lesbians would have similar goals
      regarding their relationships and, therefore, score higher on satisfaction and
      trust than heterosexual women. 50 lesbians and 50 heterosexual women were
      approached during lesbian and heterosexual social activities held at four
      colleges in the northeast and asked to complete a demographic survey and measures
      of satisfaction and trust. Findings partially supported our predictions.

PMID- 9198391
TI  - A note on measuring apprehension about writing.
AB  - Having revised Daly and Miller's 1975 unidimensional Writing Apprehension Test,
      Riffe and Stacks in 1992 proposed eight multidimensional factors derived from
      responses to 56 items in their Mass Communication Writing Apprehension Measure,
      administered to communication students to identify the various dimensions of
      apprehension about writing shared with business writers and specific to their
      major. The current authors administered the questionnaire at the beginning of an
      academic year to 419 freshmen from all undergraduate schools and majors at a
      private liberal arts university. It was hypothesized that the factors found among
      the homogeneous population of communication majors would not be replicated among
      the more heterogeneous student population. The hypothesis was partially upheld.
      Seven factors were identified. Two duplicated most items found by Riffe and
      Stacks (1992), four added items, and one was new. The results of this study
      suggest that, although the general population of students differs from students
      in mass communication, as Riffe and Stacks remarked, the groups also share
      similar content in their writing apprehension, that writing apprehension is
      multidimensional, that caution must be exercised when administering any
      instrument for the diagnostic and counseling purposes suggested by Riffe and
      Stacks, and that writing apprehension should also be investigated from the
      perspective of locus of control.

PMID- 9198392
TI  - Mathematics achievement and attitudes of senior secondary-school students in
      Transkei, South Africa.
AB  - In a study of mathematics achievement and attitudes toward mathematics, a sample
      of 266 Standard 10 (Grade 12) students (98 boys and 168 girls) from 10 senior
      secondary schools in the Umtata district of Transkei, South Africa, were
      administered a mathematics achievement test and an attitude questionnaire.
      Contrary to other studies analysis showed no significant relationship between
      students' scores on measures of mathematics achievement and attitudes.

PMID- 9198393
TI  - Comparison of the Shipley Institute of Living Scale and WAIS-R IO scores for a
      sample of public sector psychiatric inpatients.
AB  - This study examined the use of the Shipley Institute of Living Scale as a
      screening device in an intellectually low functioning psychiatric population of
      40 inpatients. Shipley IQ scores were significantly correlated .72 with Full
      Scale WAIS-R IQ scores. There was no significant difference between the mean IQ
      scores generated from the two measures. These findings suggest that the Shipley
      scale may be used in this population despite a caution by the test's publisher
      that the test should not be used in assessing intellectual functioning in
      individuals with borderline or lower intelligence.

PMID- 9198394
TI  - Parental divorce and intimate relationships of young adults.
AB  - This study examined associations among parental divorce, family conflict, sex,
      and young men's and women's achievement of intimacy. Analyses indicated that
      family conflict and sex, but not divorce, were significantly related to intimacy.
      Examination of those within the divorced group suggest that time of divorce,
      along with family conflict, were related to intimacy.

PMID- 9198395
TI  - Effects of sex of caller, implied sexual orientation of caller, and urgency on
      altruistic response using the wrong number technique.
AB  - This study using the wrong number technique focussed on the effects of sex of
      caller, sexual orientation of caller, and urgency on the altruistic response of
      making a call. In a 2 (sex) x 2 (heterosexual or homosexual) x 2 ("last quarter"
      or "no more change") factorial design the dependent variable was the number of
      seconds taken for a return telephone call. A woman or man asking for a boyfriend
      or girlfriend were helped faster than homosexual ones. Further research exploring
      the ways people of different sexual orientations are responded to is recommended.

PMID- 9198396
TI  - Weight loss for women: studies of smokers and nonsmokers using hypnosis and
      multicomponent treatments with and without overt aversion.
AB  - Study 1 compared overweight adult women smokers (n = 50) and nonsmokers (n = 50)
      in an hypnosis-based, weight-loss program. Smokers and nonsmokers achieved
      significant weight losses and decreases in Body Mass Index. Study 2 treated 100
      women either in an hypnosis only (n = 50) or an overt aversion and hypnosis (n =
      50) program. This multicomponent follow-up study replicated significant weight
      losses and declines in Body Mass Index. The overt aversion and hypnosis program
      yielded significantly lower posttreatment weights and a greater average number of
      pounds lost.

PMID- 9198397
TI  - Making attributions to the physician following closing arguments of a simulated
      medical malpractice suit: jurors' sex, health locus of control, and locus of
      authority.
AB  - This study examined jurors' health locus of control, locus of authority, sex, and
      attribution assigned to the physician in a simulated trial by subject-jurors.
      Subjects viewed videotaped closing arguments of a fictionalized medical
      malpractice case and assigned fault to each party in the case. The primary
      finding was that women tended to assign greater responsibility (57.00%) to the
      physician than did men (37.92%).

PMID- 9198398
TI  - Social correlates of suicide rates in Portugal.

PMID- 9198399
TI  - Sense of coherence, negative affectivity, and general health in farm supervisors.
AB  - Interview schedules were administered, 9 mo. apart, to 79 male first-line
      supervisors. The first included the 13-item Sense of Coherence scale (Antonovsky)
      and the PANAS, from which the Negative Affectivity scale was used; the second
      included two graphic rating scales for general health. Scores on Sense of
      Coherence and Negative Affectivity correlated -.30, indicating that the
      relationship is not always strong enough to assume that the former scale measures
      the inverse of the latter. Scores on Sense of Coherence and health ratings
      correlated .26, reducing to .25 with Negative Affectivity partialled out. This
      supports the validity of the Sense of Coherence scale as a measure of
      Antonovsky's "salutogenesis" construct.

PMID- 9198400
TI  - Psychosocial beliefs of medical students planning to specialize in family
      medicine.
AB  - The psychosocial orientation of fourth-year medical students planning careers in
      family medicine was compared to those selecting other specialties using the
      Physician Belief Scale. This scale has shown that practicing family physicians
      have a greater psychosocial orientation than those in other specialties such as
      internal medicine. The current study was done to see whether students choosing
      family medicine already have this greater orientation before they begin training
      as residents. 664 fourth-year medical students received surveys during their
      senior year and 378 (57%) returned completed surveys. Female students had a
      significantly greater psychosocial orientation than their male peers, but there
      were no significant differences between students planning residencies in family
      medicine and those selecting other residencies. The greater orientation of family
      doctors would appear to be a product of further training and experience either
      during residency or later during the actual practice of family medicine.

PMID- 9198401
TI  - Can scores on alexithymia distinguish patients with peptic ulcer and erosive
      gastritis?
AB  - This study examined alexithymic characteristics of 57 patients with peptic ulcer
      and 198 with erosive gastritis. The prevalence rate of alexithymia, as measured
      on the 20-item Toronto Alexithymia Scale, was significantly higher for the peptic
      ulcer group (51%) than for the erosive gastritis group (21%). Scores of the
      Profile of Mood States were significantly higher for the peptic ulcer group than
      for the erosive gastritis group. The alexithymia scores were significantly
      correlated with the scores on the Profile of Mood States. However, discriminant
      analysis indicated that the alexithymia scores could account for significant
      additional variance beyond mood states as measured by the Profile of Mood States.

PMID- 9198402
TI  - Comment on "catholicism and indices of social pathology in the states".
AB  - Although some indices of social pathology were associated with the proportion of
      Roman Catholics in the states in a 1980 data set, these associations were
      confounded by the association of the proportion of Roman Catholics with the
      proportion of Jews and the urban/wealth characteristics of the states.

PMID- 9198404
TI  - Empathy and reactive depression.
AB  - Empathy and reactive depression were investigated with 53 women, from 21 to 53
      years of age, who worked or planned to work as nurses, counselors, or social
      workers. Empathy was measured using the Mehrabian and Epstein Questionnaire
      Measure of Empathic Tendency. The adapted Zung Self-rating Depression Scale was
      used to measure Depressive Symptomatology, and Paykel's Scale for Life Events was
      used to identify stressful events. A narrative questionnaire elicited additional
      information to assess stressful events and to screen clinically for endogenous
      depression. Reactive Depression scores were obtained using a best fit line to
      correct Depressive Symptomatology for severity of Life Events. A significant
      modest positive correlation of 39 was found between scores on Empathy and
      Reactive Depression.

PMID- 9198403
TI  - Affective Bicultural and Global-Human Identity Scales for Mexican-American
      adolescents.
AB  - Scales were developed to measure affective aspects of Latino, American, and
      global-human identities among first- and second-generation Mexican-American
      adolescents. Participants were 84 boys and 93 girls from the Los Angeles high
      schools. 60 were born in Mexico, and 117 were born in the United States and had
      at least one parent born in Mexico. The affective Latino and American measures
      were independent and predictably related to a behaviorally oriented measure of
      acculturation. They were also used to identify Berry's four modes of
      acculturation: Separated, Assimilated, Marginalized, and Bicultural. The four
      acculturation groups rated similarly on self-esteem and academic aspiration. The
      first and second generations each scored higher on Latino identity than on
      American identity.

PMID- 9198405
TI  - Religion and psychological well-being in later life.
AB  - A sample of 50 retired civil servants completed the Bradburn Balanced Affect
      Scale together with measures of personal prayer and public church attendance. No
      significant association emerged between psychological well-being and religion.

PMID- 9198406
TI  - Sex differences in pathological gambling using gaming machines.
AB  - With recent introduction of poker machines in Australia, there have been claims
      of increases in the number of women with gambling-related problems. Research in
      the United States indicates, however, that men have a higher incidence of
      pathological gambling. The aims of this study were to ascertain among game
      machine users in a major city in Australia whether (a) more women than men
      exhibited symptoms of pathological gambling, (b) women reported higher guilt
      associated with their gambling, and (c) gamblers' self-assessment on several mood
      states was predictive of pathological gambling. A modified version of the South
      Oaks Gambling Screen was administered to 104 users of game machines (44 men, 60
      women) sampled from patrons at gaming venues in Melbourne, Australia. Data
      indicated no significant sex difference in the proportion of pathological
      gamblers or in gambling-related guilt. Self-assessment of Happiness, Propensity
      for Boredom, and Loneliness, significantly predicted scores on the South Oaks
      Gambling Screen, with Unhappiness a significant independent predictor of
      pathological gambling. This may suggest that gambling acts to fill a need in the
      lives of unhappy people or that individuals who lack control over their gambling
      report higher unhappiness. Further research is needed to discover this
      relationship.

PMID- 9198407
TI  - Temporal association of substance abuse and self-esteem.

PMID- 9198409
TI  - Longitudinal sealing ability of mineral trioxide aggregate as a root-end filling
      material.
AB  - This study evaluated the ability of mineral trioxide aggregate (MTA) to seal the
      root end effectively. Seventy-six single-rooted, extracted human teeth were
      cleaned and shaped using a step-back technique. After root-end resection and
      ultrasonic preparation, 72 root sections were randomly allocated to three groups
      and filled with dental amalgam and cavity liner, Super-EBA, or MTA. Microleakage
      was assessed at 24 h, 72 h, 2 wk, 4 wk, 8 wk, and 12 wk, using a fluid filtration
      measurement system. MTA demonstrated excellent sealing ability throughout 12 wk
      of fluid immersion, comparable with that observed for Super-EBA. Microleakage in
      the MTA group, as well as the Super-EBA group, was significantly less (p < 0.05)
      than in the amalgam group at 24 h, 72 h, and 2 wk. At the subsequent periods,
      there were no significant differences among the three materials. In this study,
      MTA was determined to be superior to amalgam, and comparable with Super-EBA in
      preventing microleakage when used as a root-end filling.

PMID- 9198408
TI  - Ambulatory care visits of physician offices, hospital outpatient departments, and
      emergency departments: United States, 1995.
AB  - OBJECTIVES: This report describes ambulatory care visits in the United States
      across three ambulatory care settings-physician offices, hospital outpatient
      departments, and hospital emergency departments. Statistics are presented on
      selected patient and visit characteristics for aggregated ambulatory care visits
      and for each setting. METHODS: The data presented in this report were collected
      by means of the 1995 National Ambulatory Medical Care Survey (NAMCS) and the 1995
      National Hospital Ambulatory Medical Care Survey (NHAMCS). These surveys are part
      of the ambulatory care component of the National Health Care Survey that measures
      health care utilization across a variety of providers. The NAMCS and NHAMCS are
      national probability sample surveys of visits to office-based physicians (NAMCS)
      and visits to the outpatient departments and emergency departments of non
      Federal, short-stay and general hospitals (NHAMCS) in the United States. Sample
      data are weighted to produce annual estimates. RESULTS: During 1995 an estimated
      860.9 million visits were made to physician offices, hospital outpatient
      departments, and hospital emergency departments in the United States, an overall
      rate of 3.3 visits per person. Visits to office-based physicians accounted for
      81.0 percent of ambulatory care utilization, followed by visits to emergency
      departments (11.2 percent) and outpatient departments (7.8 percent). Persons 75
      years and over had the highest rate of ambulatory care visits. Females had
      significantly higher rates of visits to physician offices and hospital outpatient
      departments than males did. Less than two-thirds of ambulatory care visits by
      black persons were to physician offices. There were an estimated 126.1 million
      injury-related ambulatory care visits during 1995, or 48.2 visits per 100
      persons.

PMID- 9198410
TI  - Microleakage of human saliva through dentinal tubules exposed at the cervical
      level in teeth treated endodontically.
AB  - This study investigated the possibility of saliva recontamination occurring
      between the root canal wall and sealer through dentinal tubules exposed after the
      cementum was removed at the cervical level by root planing and treatment with
      citric acid. Thirty-four extracted human maxillary anterior teeth were randomly
      placed into five groups after chemomechanical preparation and obturation with
      gutta-percha and sealer; the sealer was allowed to set for 48 h. A ring 3 mm
      high, at the cervical level, was subjected to root planing, with complete removal
      of the cementum. All specimens were coated with two layers of nail polish and two
      layers of sticky wax, except for the ring subjected to root planing that was
      treated with citric acid for 30 s. The specimens were exposed to human whole
      saliva for 20 to 80 days and then immersed in dye to determine microleakage.
      Specimens were cleared and measurements made to the maximum point of dye
      penetration. All of the specimens exposed to saliva showed leakage except for the
      negative control, wherein no dye penetration was seen. Where leakage was found,
      the dye penetrated between the canal walls and the sealer to increasing depths,
      proportional to the time of exposure to the saliva. Statistical analysis
      confirmed these data, evidencing a difference between the means, which was highly
      significant for all pairs.

PMID- 9198411
TI  - Effect of immediate and delayed post preparation on apical dye leakage using two
      different sealers.
AB  - Eighty freshly extracted teeth were endodontically prepared and filled with gutta
      percha and either a zinc oxide-eugenol-based sealer or AH26 to determine what
      effect these sealers, with widely differing properties, would have on apical
      microleakage after either immediate or delayed dowel space preparation. The teeth
      were randomly assigned to 1 of 4 groups, and the post space was made either
      immediately after filling or after being stored in 100% humidity for 1 wk. They
      were then immersed in a 2% methylene blue solution under vacuum, washed, and
      split longitudinally. The extent of dye penetration was read by five independent
      observers and the results analyzed. The only significant difference was in the
      delayed preparation group with zinc oxide-eugenol sealer, which showed greater
      leakage than the other groups.

PMID- 9198412
TI  - Evaluation of temporary restorations' microleakage by means of electrochemical
      impedance measurements.
AB  - The aim of this study was to quantify the changes in the watertightness of three
      temporary filling materials over 1 wk with a new electrochemical technique: the
      impedance a measurement technique. Forty sound extracted human maxillary teeth
      were selected and prepared for the measurements. They were divided into three
      groups in addition to positive and negative controls. The resistance, and
      therefore the watertightness, of the intact crown and the resistance after
      preparation of an endodontic access cavity were registered. After a randomization
      procedure, 12 teeth were obturated with Cavit G, 12 teeth with Fermit-N, and 12
      teeth with Intermediate Restorative Material (IRM). The changes in the resistance
      were measured first just after obturation (time 0), then after days 1, 2, 3, 4,
      and 7. The results showed that the IRM group was significantly more watertight
      than the Fermit-N group (p < 0.05) and much more than the Cavit G group (p <
      0.005).

PMID- 9198413
TI  - Diffusion of calcium through dentin.
AB  - The purpose of this research was to investigate whether calcium ions from a paste
      of calcium hydroxide [Ca(OH)2] and saline introduced into root canals diffuse
      through the dentin to reach the surface of the root. Six teeth were opened and
      submitted to a biomechanical process, after which all the smear layer was
      removed. The experiment was divided into three phases: dissolution, dissolution
      and diffusion I, and dissolution and diffusion II. Dissolution-each tooth, with
      no Ca(OH)2 paste in place, was sealed both cervically and apically and stored in
      700 ml of deonized water until calcium losses from the tooth into the water were
      stabilized. Dissolution and diffusion I-each root canal was filled with a paste
      of Ca(OH)2 and saline, sealed again apically and cervically, and returned to its
      solution. Dissolution and diffusion II-samples were divided into three parts: the
      control group or group 1, containing the original paste; group 2, in which the
      existing paste was diluted and the teeth were resealed and replaced in their
      solutions; and group 3, in which the existing paste was removed and a fresh paste
      was introduced. The diffusion was greater in group 3, followed by group 2. In the
      control group, we found a diffusion of calcium, which is statistically null. The
      results showed that calcium diffusion was observed, in the first 16 days, in all
      situations in which there was Ca(OH)2 paste inside the root canals.

PMID- 9198414
TI  - Effect of power settings on temperature change at the root surface when using a
      Holmium YAG laser in enlarging the root canal.
AB  - The aim of this study was to determine the maximum amount of power, in watts,
      that a Holmium YAG laser could deliver via a 245-micron fiberoptic to the canal
      surface and still not raise the temperature (delta T) of the cementum by > 5
      degrees C. Sixty single-rooted teeth were divided into three groups according to
      power selection (0.50, 0.75, and 1.00 W). The three main outcome variables were:
      change in apical temperature, change in coronal temperature, and maximum size of
      an endodontic file that could fit into the canal after lasing. The group means
      for apical delta T were: 1.00 W = 2.2 degrees C, 0.75 W = 2.68 degrees C, and
      0.50 W = 1.58 degrees C. The group means for coronal delta T were: 1.00 W = 1.15
      degrees C, 0.75 W = 0.99 degree C, and 0.50 W = 0.56 degree C. The group means
      for file size were: 1.00 W = 41.25, 0.75 W = 38.75, and 0.50 W = 40.75. The canal
      size was increased from a size 25 file up to approximately a size 40 file with
      all power groups. There were no significant differences between the groups for
      change in apical temperature (p = 0.32), coronal temperature (p = 0.17), or
      maximum file size (p = 0.86) when adjustments were made for tooth dimensions. In
      all groups studied, the delta T was < 5 degrees C. This represents a safe and
      predictable laser procedure.

PMID- 9198415
TI  - Immunohistochemical demonstration of prostaglandins E2, F2 alpha, and 6-keto
      prostaglandin F1 alpha in rat dental pulp with experimentally induced
      inflammation.
AB  - Using formalin-fixed and EDTA-decalcified cryostat sections, the
      immunohistochemical localization of prostaglandin (PG) E2, PGF2 alpha, and 6-keto
      PGF1 alpha (a stable metabolite of PGI2) was examined in normal rat and inflamed
      dental pulp. Inflammation was induced by opening the pulp chamber. There was no
      immunoreactivity for prostaglandins in normal dental pulp, whereas positivities
      for PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were demonstrated in the cytoplasm of
      macrophages and endothelial cells in the inflamed dental pulp. In addition to
      these cells, numerous pulp cells and odontoblasts existing in the inflamed pulp
      and its apical noninflamed area also were intensely stained for PGF2 alpha. Such
      an area with positive cells gradually extended in an apical direction with the
      progression of inflammation. These findings suggested that PG production from
      these host cells is involved in development of inflammation of rat dental pulp.

PMID- 9198416
TI  - Analysis of nickel-titanium versus stainless steel instrumentation by means of
      direct digital imaging.
AB  - This study compared step-back preparations in curved canals using nickel-titanium
      (Ni-Ti) K-files and stainless steel K-files. Forty canals in mesial roots of
      mandibular molars were embedded in casting resin and cross-sectioned at three
      levels: 1 to 2 mm from the apical foramen, middle of the curve, and coronal.
      Direct digital computer images were recorded before and after instrumentation.
      Superimposition of the images combined with digital subtraction computer software
      allowed direct measurement of area instrumented, distance of transportation, and
      shape analysis. The computer software calculated absolute center of gravity for
      each image analyzed to get a full 360-degree interpretation of the canal
      transport. Time of instrumentation was recorded. Results showed Ni-Ti files to
      cause significantly less transportation and remain more centered at the apical
      level (p < 0.05). Area removed by Ni-Ti and stainless steel files was not
      significantly different (p < 0.05). Time of instrumentation was not significantly
      different for Ni-Ti and stainless steel instruments (p < 0.05). Cross-sectional
      shape of the instrumented canal was not significantly different (p < 0.05).

PMID- 9198417
TI  - An assessment of the ability of various materials to seal furcation canals in
      molar teeth.
AB  - Ninety-seven maxillary and mandibular molar teeth were evaluated for the presence
      of naturally occurring furcation canals using the fluid filtration method. Only
      one specimen demonstrated a naturally occurring patent furcation canal. An
      artificial furcation canal was created with a 0.33-mm drill bit in the 96 teeth
      lacking naturally occurring furcation canals. Fluid filtration measurements were
      made before and after the artificial canal was made, and these served as the
      negative and positive controls for each tooth. The 96 teeth were randomly divided
      into eight equal groups, and the floor of the pulp chambers was sealed using 3 mm
      of either Tytin or Dispersalloy amalgams, Vitremer, FluoroCore, gutta-percha with
      sealer, Tytin with Ali-Bond 2 or Amalgambond, or Dispersalloy with Ali-Bond 2.
      Analysis of measured microleakage at 3 months indicated that Tytin amalgam used
      alone had significantly more microleakage than all other materials; however, this
      difference did not exist when bonding agents were used with Tytin. All materials
      leaked significantly less than the positive controls.

PMID- 9198418
TI  - Development of a quantitative sampling method for periapical exudates from human
      root canals.
AB  - A quantitative method for collection of periapical exudates on endodontic paper
      points is described. In a pilot study, it was revealed that the relationship
      between fluid volume and wetted length of paper points had a highly significant
      curvilinear relationship (p < 0.0001), and a highly significant positive linear
      relationship was found to describe eluted and absorbed interleukin (IL)-1 beta
      activities from paper points. Periapical exudates from 29 root canals with apical
      periodontitis were collected using this method, and IL-1 beta activities in
      clinical specimens were measured. Periapical exudates (0.15 to 26.7 microliters)
      were recovered, and the range of IL-1 beta concentration was 0.1 to 179.5 ng/ml.
      These results showed that this sampling method was useful to analyze
      immunological changes in periapical lesions.

PMID- 9198419
TI  - An in vivo evaluation of Root ZX electronic apex locator.
AB  - The Root ZX has been introduced recently as a device capable of performing
      accurately in the presence of sodium hypochlorite, blood, water, local
      anesthetic, and pulpal tissues. The Root ZX was used to locate the apical foramen
      in 26 root canals of vital teeth. After extraction of the teeth, a
      stereomicroscope was used to confirm visually the relationship of the tip of the
      endodontic file to the apical foramen. The Root ZX located exactly the apical
      foramen in 17 canals (65.4%), was short in 1 canal (3.8%), and was overextended
      in 8 canals (30.8%). When a potential error of +/-0.5 mm from the foramen is
      accepted as a tolerable range for the clinical application of an electronic apex
      locator, the Root ZX was able to locate the foramen within this range in 25 teeth
      for a clinical accuracy rate of 96.2%.

PMID- 9198420
TI  - Accidental swallowing of a dental clamp.

PMID- 9198421
TI  - Using rectified turpentine oil in endodontic retreatment.
AB  - A clinical technique for using rectified turpentine oil to soften and dissolve
      gutta-percha to facilitate retreatment is described. Turpentine oil should be
      heated to 160 degrees F (71 degrees C) to increase its reactivity before delivery
      to the canal space.

PMID- 9198422
TI  - Effect of calcium hydroxide and combinations of Ledermix and calcium hydroxide on
      inflamed pulp in dog teeth.
AB  - The effects of Ledermix+calcium hydroxide (Ca(OH)2) or Ca(OH)2 alone on inflamed
      pulp tissues of dogs were studied. Fifty-nine upper incisor teeth of 10 dogs were
      used. Class V cavities were prepared and filled with amalgam after placement of
      decayed dentin particles. After 7 days, the decayed dentin and alloy were
      removed, and the pulps of the teeth were exposed. Ledermix and Ca(OH)2 mixtures
      or Ca(OH)2 alone were applied to the cavities. At the end of 7, 30, and 90 days,
      the teeth were extracted and examined histopathologically. Inflammation was found
      to be more prevalent in the 7- and 30-day groups that were treated with the
      Ledermix+Ca(OH)2 combination, whereas fibrosis and necrosis were nearly similar
      in both groups. In the 90-day groups, no inflammation was seen. No difference
      between the two 90-day groups with regard to reparative dentin was found.

PMID- 9198423
TI  - Alterations in macrophages after exposure to root canal filling materials.
AB  - The process of engulfment of overextended root canal filling materials was
      investigated in rat peritoneal macrophages in vitro. Root canal filling materials
      tested were Finapec APC, Sealapex, Canals-N, and Canals. The phagocytosis rate of
      macrophages for the Finapec APC was significantly (p < 0.05) higher than that for
      other three root canal filling materials. That for Canals was the lowest. About
      95% of the cells exposed to Finapec APC were viable at 60 and 120 min. For Canals
      the percentage was 74% and 63% at 60 and 120 min, respectively. Ruffle formation
      in macrophages was observed by scanning electron microscopy after exposure to
      Finapec APC for 60 or 120 min. Many vacuoles were observed in macrophages exposed
      to Canals for 60 min. It was concluded that the phagocytic rate of macrophages
      for Canals that showed a strong cytotoxicity was lowest and that the rate for
      Finapec APC that showed a low cytotoxicity was the highest.

PMID- 9198424
TI  - Steroids reduce the periapical inflammatory and neural changes after pulpectomy.
AB  - Root canal treatment, including obturation with gutta-percha and a zinc oxide and
      eugenol sealer, was conducted, under general anesthesia, on the canine teeth of
      12 young ferrets. Six of the ferrets were given 0.5 mg/kg dexamethasone daily.
      Three months after the root canal treatment, under general anesthesia, the
      animals were perfused with fixative and the canine periapical tissues prepared
      for histological examination. The extent of periapical inflammation was measured
      and the degree of neural sprouting in the periodontal and subapical regions
      estimated. Periapical lesions in steroid-treated animals were 30% of the size of
      those in untreated animals. Innervation density in the subapical region of the
      steroid-treated animals was lower than that in the animals who did not receive
      steroids and not significantly different from controls. Reduction in periapical
      inflammation induced by systemic steroids is accompanied by a reduction in neural
      sprouting.

PMID- 9198425
TI  - Clinical evaluation of bacterial leakage of endodontic temporary filling
      materials.
AB  - This study was an in vivo comparison of the bacterial leakage associated with
      three endodontic temporary restorative materials: Cavit, Intermediate Restorative
      Material (IRM), and TERM. The access openings of 51 endodontically treated teeth
      were randomly sealed with a 4-mm thickness of one of the three materials. Three
      wk after placement of each temporary restoration, bacterial leakage was evaluated
      by sampling from beneath the temporary restoration and then culturing the samples
      both aerobically and anaerobically. Positive growth occurred in 4 of 14 TERM
      samples and in 1 of 18 IRM samples. Cavit did not demonstrate leakage in any of
      the teeth in which it was used. Cavit provided a significantly better seal than
      TERM over the study period.

PMID- 9198426
TI  - Sealing ability of five different retrograde filling materials.
AB  - The sealing ability of Amalgam, Harvard-Cement, Diaket, gold-leaf, and Ketac-Endo
      as retrofilling materials was investigated. Paper cones were fixed with Harvard
      Cement in the instrumented roots of 100 extracted human incisors. Apicectomy was
      performed and a 2-mm-deep retrograde cavity was prepared. Teeth were assigned to
      five groups (n = 20); each group received a different filling material. Surfaces
      of the roots were isolated with nail polish. Teeth, were stored in 1% methylene
      blue dye for 72 h. Roots were sectioned, and the depth of dye penetration was
      evaluated through a stereomicroscope. Retrofills with Ketac-Endo showed
      significantly less leakage compared with amalgam. There was no significant
      difference between the amalgam and Diaket groups. The sealing ability of Harvard
      Cement and gold foil was lower than amalgam. It was concluded that retrograde
      fillings with Ketac-Endo or Diaket can be considered as alternatives for amalgam.

PMID- 9198427
TI  - A scanning electron microscopic evaluation of the debridement capability of
      sodium hypochlorite at different temperatures.
AB  - The effect of raising the temperature of the irrigant solution on the smear layer
      was evaluated in the middle and apical third of 22 human upper incisors. A 5%
      sodium hypochlorite (NaOCl) solution was used at 21 degrees C and at 50 degrees
      C. After hand instrumentation and treatment with the irrigant, teeth were
      fractured into halves and examined by scanning electron microscopy.
      Characteristics of the smear layer in the two groups of specimens were compared.
      In the middle third, where NaOCl had been used at 50 degrees C, the smear layer
      was thinner and made of finer, less well-organized particles than where it had
      been used at 21 degrees C. In the apical third, the smear layer was of almost the
      same thickness in the two groups of specimens, although the particles were finer
      where the NaOCl had been used at 50 degrees C.

PMID- 9198428
TI  - Evaluation of coronal microleakage after endodontic treatment.
AB  - A new method is suggested for placing a coronal seal in the orifice of the root
      canal right after root canal therapy. Root canal therapy was done on 94 extracted
      human maxillary centrals. Three mm of the coronal gutta-percha was replaced by
      either Cavit, TERM, or amalgam with cavity varnish. After thermocycling and 2 wk
      of immersion in dye, the amount of dye penetration was measured. The results
      showed that amalgam with two coats of cavity varnish sealed significantly better
      than Cavit and TERM. However, Cavit and TERM were still significantly better than
      a positive control group.

PMID- 9198429
TI  - A comparison of canal preparation using the K-file and Lightspeed in resin
      blocks.
AB  - Twenty-four resin blocks with simulated curved canals of approximately 38 degrees
      were divided into two groups of 12 each. One group was instrumented with
      stainless steel K-files and the other group with nickel-titanium Lightspeed
      Rotary instruments. The efficiency of canal preparation was evaluated at 1, 3, 5,
      and 7 mm from the apex using magnified images (x4) of the radiographed blocks.
      The results showed that K-files caused more widening at the apical end, with a
      higher incidence of transportation, zipping, and elbow formation. The Lightspeed
      instrument stayed centered in the canals maintaining the central axis, with
      minimal incidence of transportation, elbow formation, and zipping. Thus, the
      Lightspeed instrument may be considered more suitable for efficient preparation
      of curved canals than the K-type file.

PMID- 9198430
TI  - Retrograde root filling with dentin-bonded modified resin composite.
AB  - A retrograde root-end cover with a special resin composite (Retroplast) combined
      with the dentin bonding agent Gluma (Bayer AG) has been used since 1984 by the
      authors. Its content of silver, added to promote radiopacity, has been found to
      lower the working time and storage stability of the composite and might cause
      discolorations. Since 1990, silver has therefore been replaced with ytterbium
      trifluoride, which eliminates these side effects. The purpose of this study was
      to compare the clinical results obtained with these two resin composites and to
      evaluate the healing results after several years in function. Apical fillings
      (351) with the modified Retroplast showed the following radiographic healing
      pattern 1 yr after surgery: 80% complete healing, 2% scar tissue, 12% uncertain
      healing, and 6% failure. No significant difference in this healing pattern was
      found, compared with that obtained with the silver-containing Retroplast. Cases
      with ytterbium trifluoride classified as scar tissue and uncertain healing at 1
      yr when examined at 2 to 4 yr postoperatively showed 89% complete healing. 0%
      scar tissue, 1% uncertain healing, and 9% failure. This result is significantly
      different from that obtained 1 yr after surgery. Based on calculations, it was
      predicted that with time 90% will become complete healing, whereas 10% will
      become failure.

PMID- 9198431
TI  - Anesthetic efficacy of the intraosseous injection after an inferior alveolar
      nerve block.
AB  - The purpose of this study was to determine the contribution of the intraosseous
      (IO) injection to the inferior alveolar nerve (IAN) block in human first molars.
      Using a repeated-measures design, 40 subjects randomly received either a
      combination IAN block + IO injection (on the distal of the first molar) using 2%
      lidocaine with 1:100,000 epinephrine or an IAN block+mock IO injection (gingival
      penetration only) at two successive appointments. The first molar and adjacent
      teeth, and contralateral canine (+/-controls) were blindly tested with an
      Analytic Technology pulp tester at 2-min cycles for 60 min. An 80 reading was
      used as the criterion for pulpal anesthesia. One hundred percent of the subjects
      had lip numbness with the IAN block. For the first molar, anesthetic success,
      defined as achieving an 80 reading within 15 min and keeping this reading for 60
      min, was 42% with the IAN and 90% with the IAN + IO. Anesthetic failure defined
      as never achieving two 80 readings during the 60 min was 32% with the IAN and 0%
      with the IAN + IO. The onset of anesthesia was immediate with the IO injection.
      Eighty percent of the subjects sampled had a subjective increase in heart rate
      with the IO injection. The IO injection and postinjection questionnaire recorded
      low pain ratings.

PMID- 9198432
TI  - Effect of ultrasonic vibration on post removal in extracted human premolar teeth.
AB  - The purpose of this study was to determine the effectiveness of ultrasonic
      vibration in removing Paraposts from extracted teeth. Paraposts were cemented in
      mandibular premolars to a depth of 9 mm with zinc phosphate cement and the teeth
      placed in four groups. Group 1 received no vibration. Group 2 received vibration
      for 4 min, group 3 received vibration for 12 min, and group 4 received vibration
      for 16 min. Tensile forces were applied to the posts and mean dislodgment forces
      compared. The mean force (kg) required to dislodge the Parapost in group 1 was
      24.92 +/- 1.64 SEM; in group 2, 25.01 +/- 1.80; in group 3, 24.08 +/- 2.29; and
      in group 4, 12.41 +/- 2.60. There was a significant difference between group 4
      and groups 1 to 3 (p = 0.0003). Results of this study indicate that 16 min
      ultrasonic vibration is an effective method for removing Paraposts from human
      premolar teeth.

PMID- 9198433
TI  - A new ultrasonic canal preparation system with electronic monitoring of file tip
      position.
AB  - A new ultrasonic root canal preparation system has been developed that
      electronically monitors the location of the file tip during all instrumentation
      procedures. The Root ZX has been adapted for this purpose, and its filter circuit
      effectively cuts out the large spike noise of the ultrasonic unit. During
      enlargement of the canal, the ultrasonic vibration of the file can be stopped at
      any desired position on the meter. Extracted human tooth models with
      electronically measurable canals were used to test the device. Pre- and
      postoperative shapes of the root canals were evaluated using contact
      microradiography. The autostop mechanism worked correctly. Using a weak power and
      fine files, straightening, ledge formation, and file breakage were minimal. It
      seems that this system minimized the danger of overinstrumentation and could be
      safely applied in clinical practice.

PMID- 9198434
TI  - Management of a maxillary canine with dens invaginatus and a vital pulp.
AB  - A case is presented that demonstrates successful management of a maxillary canine
      with dens invaginatus (Oehlers' type 3 invagination) with associated chronic
      periradicular periodontitis and a vital pulp. Debridement and obturation of the
      invaginated space resulted in resolution of the associated periradicular
      radiolucency. Pulp vitality was retained after endodontic treatment of the
      invagination.

PMID- 9198435
TI  - Current literature--endodontics.

PMID- 9198436
TI  - Wound healing after mucoperiosteal surgery in the cat.
AB  - The purpose of this study was to examine possible tissue-dependent differences in
      rate of healing after mucogingival flap surgery. After intrasulcular incision and
      a vertical-releasing incision distal to the maxillary and mandibular cuspids,
      buccal, full-thickness mucogingival flaps were raised in four quadrants of 10
      adult cats. The triangular flaps were left open for 30 min and then repositioned
      and sutured. Tissue reactions were studied histologically after 1, 3, 7, 14, and
      28 days of healing. Although new collagen occasionally was observed in the wound
      space in the free gingiva at 3 days, collagenous union between the cut
      dentogingival fibers and the flap seemed well established at 7 days. Flap
      reattachment to the denuded cortical bone was seen at 14 days in the region of
      the attached gingiva. In the region of the alveolar mucosa, however, residual
      coagulum and inflammatory reaction was present as late as at 28 days in several
      specimens. These observations indicate a marked difference in rate of healing
      among the different interfaces involved. These variations seem to be related to
      variations in size of the resulting wound space when a full-thickness
      mucoperiosteal flap is readapted over cervical root surfaces, alveolar bone
      crest, and denuded cortical bone, respectively.

PMID- 9198437
TI  - Interpretation of chemically created periapical lesions using direct digital
      imaging.
AB  - Perchloric acid (70%) was used to create simulated periapical lesions in tooth
      sockets of 15 dentate cadaver jaw specimens. Using the Trophy USA direct digital
      radiographic system, linear images were captured at selected time intervals after
      initial acid application and altered by contrast reversal, pseudocolor
      enhancement, and two forms of histogram equalization. The 525 total images were
      randomized for display on a computer monitor for evaluation by five endodontists.
      Images were evaluated twice by each rater, with viewings 1 to 2 wk apart.
      Statistical analysis determined interrater variability, intrarater
      reproducibility, and the relative merits of each enhancement technique. At 8, 12,
      16, and 24 h after acid application, both techniques of histogram equalization
      yielded a statistically significant improvement over reverse contrast in
      perception of periapical patholais. Linear and pseudocolor-enhanced images were
      also significantly more diagnostic than reverse contrast at 12, 16, and 24 h.
      Intrarater reproducibility showed moderate agreement, but analysis showed only a
      fair level of interrater agreement.

PMID- 9198438
TI  - Canal debridement: effectiveness of sodium hypochlorite and calcium hydroxide as
      medicaments.
AB  - The action of chemicals such as calcium hydroxide (Ca(OH)2) and sodium
      hypochlorite (NaOCl) that are used as tissue solvents may be enhanced by
      prolonged contact. The objective of this study was to determine if sealing
      Ca(OH)2 and NaOCl into the canal space would improve debridement of both the main
      canal and areas inaccessible to files. Mesial root canals of 75 freshly extracted
      mandibular molars were step-back hand-instrumented. Another six molars were
      controls. Either Ca(OH)2, NaOCl, or no medication was sealed in the canals for 1
      or 7 days. Canals were finally irrigated with H2O and prepared for histological
      evaluation. The cleanliness of main canals and inaccessible areas (isthmi and
      fins) at the apical, middle, and coronal thirds was examined, scored, and
      compared by nonparametric statistical analysis. Results showed no significant
      differences among different groups in either the 1-day or 7-day time intervals in
      either the main canal or inaccessible areas. Instrumentation combined with NaOCl
      irrigation alone accounted for the removal of tissue in the main canal. In
      conclusion, in this system, prolonged contact with Ca(OH)2 and NaOCl was
      similarly ineffective; neither contributed significantly to canal debridement.

PMID- 9198439
TI  - Transient effects of low-energy CO2 laser irradiation on dentinal impedance:
      implications for treatment of hypersensitive teeth.
AB  - This study evaluated the effect of CO2 laser irradiation on dentinal impedance by
      passing known cyclic potentials across dentinal wafers mounted as a window in an
      electrolytic cell and measuring the resulting electrical impedance. Wafers were
      equilibrated in 0.1 M of KCl. The wafer specimens were irradiated with a CO2
      laser (12 W, 0.1 ms, energy density 1.25 J/cm2). The time for impedance
      equilibration after irradiation was compared with equilibration after mounting.
      Mounted samples required 48 h to approach equilibrium in the electrolyte. After
      laser irradiation, impedance of previously equilibrated samples also required 48
      h to equilibrate. This, along with exponential curve fitting, confirmed that
      laser treatment reintroduced a transient alteration in impedance. Equilibration
      time after irradiation and the mounting were similar. Dentin desociation
      apparently caused this transient impedance. Energy dispersive X-ray analysis
      confirmed the disappearance of K+Cl- after irradiation. Therefore, laser
      irradiation may cause dentinal desociation, yielding temporary clinical relief of
      dentinal hypersensitivity until rehydration occurs.

PMID- 9198440
TI  - In vitro evaluation of the cytotoxicity of pure eugenol.
AB  - The aim of this study was to assess the cytotoxicity of pure eugenol in an in
      vitro method by diluting it to various concentrations in alcohol and determining
      the maximum noncytotoxic concentration. We used solutions of eugenol and ethyl
      alcohol that are soluble in water in any given proportion. The cytotoxicity of
      the alcohol itself was determined by using a dose-response curve for
      concentrations of between 0.017 M and 1.7 M. Various strength concentrations
      (0.015 to 947 microM) of eugenol in alcohol were prepared; 20 microliters (0.34
      M) of ethyl alcohol was added to 1 ml of cell medium. The experiment showed that
      pure eugenol is toxic for human gingival fibroblasts. Eugenol in an alcohol
      solution at concentrations of < 1.9 microM is noncytotoxic.

PMID- 9198441
TI  - Bacterial leakage in endodontics: an improved method for quantification.
AB  - A new method for studying leakage of root fillings using the bacterium
      Pseudomonas fluorescens ATCC 13525 is described. The presence of the
      microorganism is detected by fluorimetry and can thus be used to measure the
      depth of penetration from the root apex toward the crown of the tooth. This
      system, applied to a number of methods of root canal filling, showed that
      procedures involving compaction of the gutta-percha gave a more effective seal
      than the use of a paste sealer with uncondensed gutta-percha. There was no
      statistically significant difference between the leakage results from the
      lateral, vertical, and thermomechanical condensed techniques.

PMID- 9198442
TI  - Lateral condensation of small, curved root canals: comparison of two types of
      accessory cones.
AB  - This study compared the quality of the obturation of small, curved root canals
      laterally condensed with a medium-fine (MF) finger spreader and one of two types
      of accessory cones. Thirty small, curved canals of permanent molars were cleaned
      and shaped, then randomly separated into two groups. They were obturated with a
      standardized master cone and either MF conventional accessory cones of #25
      standardized accessory cones. Cross-sectional outs were made at the 2-mm and the
      4-mm apical levels. Digitized tracings were made from photomicrographic slides of
      the cross-sections to determine the percentage of gutta-percha within the canal
      areas of each cross-section. Statistical analysis revealed no significant
      difference between the two groups. Results of this study indicate there is no
      difference in the quality of obturation when using a MF finger spreader with
      either MF or #25 accessory cones.

PMID- 9198443
TI  - Enhanced surface hardness by boron implantation in Nitinol alloy.
AB  - Boron implantation into Nitinol alloy has a potential for developing improved
      Nitinol root canal instruments with excellent cutting properties, without
      affecting their superelastic bulk-mechanical properties. The surface hardness of
      nickel-titanium (NiTi) alloy, also known as "Nitinol" (50 atm% nickel+50 atm%
      titanium), has been improved by ion-beam surface modification. With an
      implantation dose of 4.8 x 10(17) boron/cm2, a high concentration of boron (30
      atm%) is incorporated into NiTi alloy by 110 keV boron ions at room temperature
      (25 degrees C). Boron-implanted and unimplanted (pure) Nitinol alloys show
      surface hardness of 7.6 +/- 0.2 and 3.2 +/- 0.2 GPa, respectively, at the
      nanoindentation depth of 0.05 micron. The ion-beam-modified NiTi alloy exceeds
      the surface hardness of stainless steel.

PMID- 9198444
TI  - Chloroform uptake by gutta-percha and assessment of its concentration in air
      during the chloroform-dip technique.
AB  - The use of chloroform as an adjunct to the practice of endodontics has been a
      matter of debate. In the present study the chloroform uptake of gutta-percha
      cones was determined by a gravimetric assay for different times of chloroform
      dip. In conjunction with an assessment of the amount of gutta-percha dissolved
      during dip, this provided an estimate of the amount of chloroform that patients
      are exposed to in clinical conditions. An assay was also performed of the
      chloroform concentration in the air in a dental office. Chloroform uptake was
      shown to increase with an increasing dipping time. There also seems to be a
      difference in this uptake between pure chloroform and a chloroform preparation
      with colophonium. The concentration levels of chloroform evaporated during the
      practice of chloroform dip within a dental office do not exceed the safety
      limits.

PMID- 9198445
TI  - A clinical study of direct pulp capping applied to carious-exposed pulps.
AB  - Direct pulp capping of carious-exposed pulp was performed on 44 teeth. We
      evaluated the success rates of these cases, and analyzed the relationships
      between the success rates and their clinical findings. Furthermore, we examined
      the length of time necessary for adequate postoperative follow-up. The success
      rate in this study was 81.8%. Age of the patients, type of teeth, responses to
      thermal stimuli and percussion, and the diameter of pulpal exposure had no
      bearing on the success rate. However, the degree of bleeding on pulpal exposure
      was related to the success rate (p = 0.042). The success rates of cases in which
      postoperative follow-up periods were 3 to 18 months were similar (80 to 83%),
      whereas those with follow-up for 21 months (91.7%) and 24 months (100%) showed
      higher success rates. These results showed that direct pulp capping was
      applicable to carious-exposed pulp, and the degree of bleeding is indicative of
      the prognosis of this treatment. The length of time necessary for adequate
      postoperative follow-up was suggested to be 21 months.

PMID- 9198446
TI  - Incidence of pulp necrosis subsequent to pulp canal obliteration from trauma of
      permanent incisors.
AB  - Little long-term data are available on the frequency by which pulp canal
      obliteration (PCO) subsequent to trauma leads to pulp necrosis (PN). In this
      study, 82 concussed, subluxated, extruded, laterally luxated, and intruded
      permanent incisors presenting with PCO were followed for a period of 7 to 22 yr
      (mean 16 yr). At final clinical examination, 51% of the observed teeth responded
      normally to electric pulp testing (EPT). An additional 40% of the teeth although
      not responding to EPT were clinically and radiographically within normal limits.
      Yellow discoloration was a frequent finding. During the observation period,
      periapical bone lesions suggesting PN developed in seven teeth (8.5%). Twenty-yr
      pulp survival rate was 84%, as determined from life-table calculations. There was
      no higher frequency of PN in obliterated teeth subjected to caries, new trauma,
      orthodontic treatment, or complete crown coverage than intact teeth. Although the
      incidence of PN in teeth displaying PCO seems to increase over the course of
      time, prophylactic endodontic intervention on a routine basis does not seem
      justified.

PMID- 9198447
TI  - Complex odontoma as a periapical and interradicular radiopacity in a primary
      molar.
AB  - Only rarely is a mature complex odontoma seen in a periapical location and in
      association with a primary tooth. Complex odontomas usually present as a
      radiopacity with a radiolucent rim. The differential diagnosis must include
      mature fibro-osseous lesions (e.g. cementoblastoma). Complex odontomas can be
      differentiated from fibro-osseous lesions because they usually present a
      nonhomogeneous radiopacity and almost always will present as solitary lesions.
      For complex odontomas located in the periapical region, the differential
      diagnosis must include idiopathic periapical osteosclerosis. In this case, the
      presence of the radiolucent rim and the presence of denser, sharper radiopacities
      produced by enamel distinguish the odontoma.

PMID- 9198449
TI  - Current literature--Endodontics.

PMID- 9198448
TI  - Patient records and referral correspondence: a time-saving method.
AB  - This article offers a time-saving method to deal with nonroutine chart entries
      and related correspondence. The doctor should dictate an abbreviated chart entry
      and utilize copies for correspondence.

PMID- 9198450
TI  - Peak expiratory flow. Proceedings of a workshop.

PMID- 9198451
TI  - [Shortened version of the Barcelona test (II): global standard score].
AB  - The aim of this study was to determine a global scoring method for a shortened
      and version of the Barcelona Neuropsychological test (TB) of 55 items. 341
      healthy volunteers, 178 male (52.19%), and 163 female (47.1%) were studied. Age
      mean: 54.80, SD = 17.44. Subjects were stratified in five groups considering age
      and education. A scale of cut-off points was selected in order to divide the
      scores of each subtest into three bands (categories): 0 (lowest), 1
      (intermediate), 2 (highest). Raw scores (possible range 0-110) were obtained and
      then were converted to a mean of 100 and SD of 15 each normative group. Tables of
      normative data were obtained for each group. This study shows the cognitive
      profiles of the TB and a global standard score related to them. This global score
      will provide new possibilities in the neuropsychological assessment of
      neurological patients.

PMID- 9198452
TI  - [Shortened version of the Barcelona test (III): criterion validity with the ADAS
      Cog].
AB  - The aim of this study was to assess the criterion validity of a global score of
      an abbreviated version of the Barcelona Test (BTA), normalized for age and
      education, as a clinical neuropsychometric test for the assessment of cognitive
      impairment. This study made a correlational analysis between test scores of the
      BTA and scores of the cognitive part of the Alzheimer's Disease Assessment Scale
      (ADAS-Cog) adjusted for age and education. It was made in a University Hospital
      (Dementia Unit). A group of 172 subjects (74 male, 98 female) was distributed
      according the Global Deterioration Stages (GDS) from 1 to 6. GDS-1 (normal
      controls), n = 60; GDS-2 (subjective complaints), n = 27; GDS-3, n = 21, GDS-4, n
      = 22; GDS-5, n = 16; GDS 6, n = 26. All dementia patients fulfilled the
      NINCDS/ADRDA criteria. BTA global scores correlated significantly with adjusted
      scores on the ADAS-Cog (r = 0.872, r2 = 0.761), p < 0.0001. The BTA has a
      criterion validity as a clinical neuropsychometric test for the study of
      cognitive impairment.

PMID- 9198453
TI  - [Ulnar neuropathy at the elbow. Diagnosis and therapeutic criteria].
AB  - Ulnar neuropathy at the elbow (UNE) is described as a nerve injury arising from
      trauma. For practical management purposes, two general types of UNE have been
      defined. One group is comprised of those cases in which identifiable bone
      deformity is present at the elbow and the other comprises cases in which only
      nerve dysfunction is found. The concept of cubital tunnel syndrome is discussed,
      as is the importance of differential diagnosis and the use of diagnostic
      electrophysiology. Nerve transposition is considered the therapeutic measure of
      choice when UNE is a consequence of anomalous elbow, and the surgical criteria
      for cases in UNE behaves like similar to carpal tunnel syndrome is discussed.
      Electrophysiology can precisely locate the site of elbow involvement, suggesting
      either simple release of the cubital tunnel or more complex surgical procedures
      such as transposition or epicondylectomy.

PMID- 9198454
TI  - [Depressive pseudodementia in early Parkinson's disease: lessons from a case with
      long-term follow-up].
AB  - A common observation in neurological practice is parkinsonism with concomitant
      cognitive decline, an association that usually arises from various underlying
      degenerative or vascular conditions, most of which are untreatable. An elderly
      woman with no history of psychiatric disease presented complaining of memory and
      cognitive impairment serious enough to interfere with daily life activities over
      the preceding year. She soon developed a predominantly left-sided tremor,
      rigidity and bradykinesia. She had had only 2 years of formal education.
      Neuropsychological assessment showed poor performance on Wechsler memory scale
      sub-items, as well as constructional apraxia, dyscalculia, reasoning difficulties
      and gross information deficits. A 3-month trial course of levodopa was followed
      by dramatic improvement in both parkinsonian symptoms and cognitive performance,
      including a 7-point gain in the Mini-Mental Status Examination score. At the same
      time, the Beck Depression Inventory score fell from 27 (baseline) to 18. Over the
      10-year follow-up period the patient developed late levodopa syndrome and a
      persistent but mild dysthymic disorder, but never manifested dementia as defined
      by DSM-III-R criteria. This patient's case illustrates three important
      principles. First, although parkinsonism is known to be preceded by depressive
      episodes, particularly in a subgroup of younger patients, the symptoms of the
      elderly patient whose Parkinson's disease is foreshadowed by depression can mimic
      depressive pseudodementia, potentially leading to diagnostic confusion. Second,
      impaired motivation and disturbances in cognitive function are different from
      mood disorders, as the former involve the mesolimbic/mesocortical dopamine
      system, explaining the beneficial effect of levodopa on motivation and cognition
      in this patient even as mood was unaffected. Finally, depressive pseudodementia
      in Parkinson's disease does not necessarily herald the development of organic
      dementia in the long term.

PMID- 9198455
TI  - [Concurrence of short and long lasting episodes of nocturnal paroxysmal dystonia
      in an epileptic patient].
AB  - We report the case of a patient with nocturnal paroxysmal dystonia (NPD) meeting
      not only the diagnostic criteria described by Lugaresi et al. in 1981, but also
      presenting with features suggestive of underlying epilepsy as well as other
      differences from the diagnostic criteria originally described for NPD, such as
      short- and long-lasting episodes and poor response to antiepileptic drugs. The
      case we describe suggests a different entity, one that is unrelated to epilepsy
      or true NPD.

PMID- 9198456
TI  - [Evoked potentials and polycythemia vera. Letter].

PMID- 9198457
TI  - [Incapacitating lumbo-sciatica with negative CT and NMR images. The utility of
      disk-CT. Letter].

PMID- 9198458
TI  - [Shortened version of the Barcelona test (I): subtests and normal profiles].
AB  - The aim of this study was to define a shortened form of the Barcelona
      neuropsychological test to be used in clinical neurology. There was a selection
      of subtests from the original test and descriptive statistics of an enlarged
      number of normal volunteers. 341 normal subjects were studied, 178 male (52.19%)
      and 163 female (47.1%). Age mean: 54.80, SD = 17.44. Education: mean 9.0 years,
      SD: 5.4. Subjects were stratified in five groups considering age and education.
      Subtest were choose according clinical criteria and considering data from a
      previous study. Five different age and education scoring profiles were defined.
      This reduced version of the Barcelona test includes the main neuropsychological
      areas and it takes only 30-45 minutes administration. The Barcelona test meets
      practical standards in neuropsychology.

PMID- 9198459
TI  - [Disturbances in mucociliary clearance after maxillary sinus surgery.
      Experimental study].
AB  - The effect of inferior nasoantral windows on mucociliary clearance, with or
      without radical surgical removal of the maxillary sinus mucosa, was evaluated in
      five New Zealand white rabbits. Mucociliary clearance was analyzed using India
      ink as a marker and observing its distribution and flow rate. Partial and radical
      surgical removal of the mucosa, nasoantral windows, and the Caldwell-Luc
      operation were performed and mucociliary transport was studied. After three
      months, mucociliary clearance was conserved after partial resection of the sinus
      mucosa and absent after radical mucosal resection.

PMID- 9198460
TI  - [Pediculated flaps: experimental study].
AB  - Seventy dorsal flaps were created in rabbits: 18 cutaneous pedicled flaps and 7
      cutaneous free flaps: 23 myocutaneous pedicled flaps and 22 myocutaneous free
      flaps. Flap viability was compared and its predictability using subjective and
      objective tests was evaluated. Pedicled flaps had a better survival rate.
      Cutaneous fluorescence was useful for predicting flap viability.

PMID- 9198461
TI  - [Functional surgery of cholesteatoma. I. Closed techniques].
AB  - A review was made of 138 ears treated with walled-up canal tympanoplasty for
      chronic otitis media with cholesteatoma. In 66.7% of the ears, two-stage
      operations were performed. Cholesteatomas were located in the attic (72.5%),
      mesotympanum (42.8%), antrum (39.1%), and mastoid (11.6%). The most common lesion
      of the ossicular chain was incus necrosis (61.6%). Total ossicular replacement
      prosthesis (TORP) (56.5%), partial ossicular replacement prosthesis (PORP)
      (21.7%), mastoid cortical bone autograft (13%), and incus autograft (8.7%) were
      used to reconstruct the ossicular chain. After three years, 56.5% of the operated
      cars were free of complications. The rest had the following complications:
      recurrence of cholesteatoma (17.4%), perforation of the neotympanum (12.5%),
      prosthesis extrusion (9.4%), and episodes of otorrhea (4.2%). The best functional
      results were obtained with autografts (cortical and incus) and TORP.

PMID- 9198462
TI  - [Treatment of chronic snoring with CO2 laser].
AB  - Laser-assisted uvulopalatoplasty (LAUP) is an effective surgical procedure for
      treating habitual snoring. It is performed under local anesthesia as an
      outpatient procedure and consists of enlarging the oropharyngeal air space and
      restructuring the uvula, velum, and pharyngeal pillars. We used LAUP in 112
      patients with upper airway resistance syndrome (UARS) (Lipman grade II) over the
      last three years and achieve a care rate of 87.5%.

PMID- 9198463
TI  - [Sequential chemotherapy and radiotherapy in the treatment of locally advanced
      carcinoma of the head and neck].
AB  - In patients with non-resectable carcinoma of the head and neck, radiotherapy
      produces an average survival of 12 months. Neoadjuvant chemotherapy followed by
      radiotherapy has been shown to prolong survival and preserve organ structure and
      function, and to reduce systemic relapses in patients with advanced, resectable
      disease. An analysis was made of 35 patients treated with sequential chemotherapy
      and radiotherapy, 20 with non-resectable disease and 15 with resectable disease
      who refused surgery. Treatment consisted of 4 cycles of cisplatin + 5-fluoruracil
      in a 96-h continuous intravenous infusion in 16 patients, and the same treatment
      with leucovorin in 19 patients. After chemotherapy, the patients underwent cobalt
      irradiation of the primary tumor and neck. Chemotherapy produced a complete
      response rate of 46% and a partial response rate of 28%, yielding an overall rate
      of 74%. After radiotherapy, the CR increased to 63%. After 92 months of maximum
      follow-up, overall survival was 20% and median survival was 25 months.
      Locoregional relapses were the main cause of treatment failure. Our results
      suggest that sequential chemo-radiotherapy achieved encouraging CR rates with no
      significant increase in toxicity, prolonged survival in non-resectable patients,
      and enabled organ preservation in patients with resectable disease.

PMID- 9198464
TI  - [Comparative, randomized, parallel clinical study of the effectiveness and safety
      of aceclofenac vs. paracetamol in the treatment of viral pharyngoamygdalitis].
AB  - The purpose of this open, controlled, and randomized study was to evaluate the
      effectiveness of aceclofenac compared with paracetamol in improving the signs and
      symptoms of viral pharyngoamygdalitis and to evaluate the safety of both drugs.
      Thirty outpatients (age range 18-65 years) with acute viral pharyngoamygdalitis
      received either aceclofenac 100 mg/12 h or paracetamol 650 mg/ 12 h per os.
      Patients were evaluated at baseline and on days 1, 3, and 7 after beginning
      treatment. The parameters of effectiveness evaluated were: severity of
      pharyngoamygdalitis, spontaneous pharyngeal pain, saliva swallowing, and duration
      of pharyngeal pain. The results showed that the aceclofenac group had a
      significant decrease in the severity of pharyngoamygdalitis and spontaneous
      pharyngeal pain after day 1 of treatment (p < 0.001), but the paracetamol group
      showed no improvement in these parameters until day 3 of treatment (p < 0.001).
      There were no adverse reactions in either group. Therefore, patients treated with
      aceclofenac showed an earlier improvement in the signs and symptoms of acute
      viral pharyngoamygdalitis than those treated with paracetamol.

PMID- 9198465
TI  - [Appropriateness of admissions and duration of stay in an ear, nose and throat
      department].
AB  - An evaluation was made of the appropriateness of hospital admissions in the ear,
      nose, and throat surgery department of a teaching hospital. One hundred fifty-two
      clinical histories were studied. Elective surgery admissions were reviewed using
      the new Appropriateness Evaluation Protocol (AEP) for elective surgery. Non
      elective admissions and the duration of the hospital stay were reviewed with the
      adult medical-surgical AEP. In the patients who underwent elective surgery,
      admission was inappropriate in 6.2% (95% confidence interval: 2.9-12.2%). Name of
      the non-elective admissions (95% confidence interval: 0-17.8%) was inappropriate.
      Nineteen per cent of hospital days were inactive (95% confidence interval: 13.3
      26.4%).

PMID- 9198466
TI  - [Berger's disease and acquired sensorineural hearing loss].
AB  - A relation between kidney and inner ear disease, specifically neurosensorial
      hearing loss, has been established. Likewise, the role of tonsillitis in certain
      glomerulonephritides is well known. A case of post-streptococcal mesangial
      glomerulonephritis with IgA deposit (Berger's disease) and neurosensorial hearing
      loss is reported. The absence of any relevant family or personal history suggests
      an immunological origin for both disorders.

PMID- 9198467
TI  - [Anomalies of the facial nerve].
AB  - An anomaly of the tympanic segment of the facial nerve in an adult cadaver
      specimen is reported. The second portion of the facial nerve crossed between the
      stapedal pillars. The rarity of this anomaly, particularly in a well constituted
      temporal bone, is discussed.

PMID- 9198468
TI  - [Malignant fibrohistiocytoma in otorhinolaryngology. Review of two cases].
AB  - Fibrohistiocytomas are soft-tissue tumors of histiocytic origin that have a
      variety of histological patterns. Although cases of malignant fibrohisticytoma
      (MFH) of the head and neck have been reported with increasing frequency in recent
      years, they can be considered rare. However, they probably are more frequent than
      thought because of the different designations that the disease has received and
      confusion among clinicians and pathologists regarding these tumors. We report two
      cases of MFH of the tonsil and larynx, respectively. The histopathological
      diagnostic criteria, therapeutic indications, and prognosis evaluation are
      described.

PMID- 9198469
TI  - [Dysphagia as a symptom of diffuse idiopathic skeletal hyperostosis (Forestier
      Rotes disease). A case report and literature review].
AB  - Swallowing disorders can be caused by cervical spine diseases, such as diffuse
      skeletal hyperostosis (DISH). This entity is diagnosed as a cause of dysphagia
      only after excluding all other possible causes. We report a case in which
      dysphagia was the initial symptom of DISH. The most important clinical and
      diagnostic aspects of the disease are discussed.

PMID- 9198470
TI  - [Mandibular actinomycosis].
AB  - We report a case of mandibular actinomycosis secondary to dental surgery in a 19
      year-old male. The major features of this clinical entity are described. Loss of
      the integrity of the oral mucosa was the determinant factor in our case.
      Systematic realization of panoramic radiographs of the jaw is proposed as a means
      of excluding lower maxillary involvement secondary to Actinomyces infection.

PMID- 9198471
TI  - [Monomorphic adenoma of basal cells in a minor salivary gland].
AB  - Tumors of the minor salivary glands represent 15% of all salivary gland tumors.
      Monomorphic adenoma is an uncommon histological type that usually is located in
      the parotid gland, minor salivary glands of the upper lip and less frequently,
      palate. The clinical and histological features of a case of palatal monomorphic
      adenoma that was diagnosed and treated in our hospital are described.

PMID- 9198472
TI  - [Surgical treatment of hairy black tongue].

PMID- 9198473
TI  - [Comments on the treatment of rhinocerebral mucormycosis].
AB  - Rhinocerebral mucormycosis is a serious infectious disease with a high mortality
      rate that requires early medical treatment. Liposomal amphotericin B is the
      medical treatment of choice because of its low renal toxicity and good tissue
      diffusion. Surgical treatment is necessary, even if all affected areas cannot be
      reached. The surgical indication should be based on individual characteristics
      and disease evolution. The case of a 56-year-old man with rhinocerebral
      mucormycosis caused by Rhizopus and treated with liposomal amphotericin B and
      extensive rhino-orbital surgical treatment is commented.

PMID- 9198474
TI  - [Activation of proto-oncogene c-fos in the auditory tract of rats stimulation
      with wide-band noise].
AB  - The pattern of expression of the proto-oncogene c-fos was mapped in the auditory
      pathway of Wistar rats kept in three different experimental conditions: a) a
      dark, soundproofed room; b) with exposure to usual environmental laboratory
      noise, and c) with exposure to wide-band noise. Under control conditions (a and
      b), scattered labeled neurons were found in the ventral periolivary nucleus,
      lateral lemniscus nuclei, inferior colliculus, medial nucleus of the medial
      geniculate body, and in three divisions of the temporal auditory cortex. Sound
      stimulation (c) increased the number of fos-like-immunoreactive (FLI) nuclei in
      all the auditory pathway structures. FLI nuclei were strong in the dorsal
      cochlear nucleus, anterior and posterior ventral cochlear nuclei, all the
      superior olivary complex nuclei, lateral lemniscus nuclei, all areas of the
      inferior colliculus, medial geniculate body, and the three temporal auditory
      areas, which showed a barrel pattern. Comparison of these results with the
      literature indicated that fos activation is not merely a sign of transitory
      neural activation, but a long-term neural processing pathway that is conditioned
      by factors such as the frequency, intensity, duration, and direction of the
      auditory stimulus.

PMID- 9198475
TI  - [Changes in the nuclear morphometry in oropharyngeal epidermoid carcinoma after
      induction chemotherapy].
AB  - A cytomorphic, stereological study was made by computerized image analysis of six
      nuclear morphometric variables and one stereological nuclear variable. Variables
      were measured on 150 randomly selected tumor cells in oropharyngeal biopsies from
      44 patients with oropharyngeal cancer who had not responded completely to
      induction chemotherapy. The nuclei of tumoral cells were larger (mean nuclear
      area, perimeter, and volume), more rounded, and had a less irregular nuclear
      contour index.

PMID- 9198476
TI  - [Anatomic features of the middle ear in the gerbil. Scanning electronic
      microscopic study].
AB  - The surgical anatomy of the middle ear was studied in 20 adult gerbils (Meriones
      unguiculatus) by microdissection and scanning electron microscopy. The most
      significant finding was a well pneumatized tympanic bulla, which facilitated the
      identification of useful anatomical landmarks for middle and inner ear
      dissection. The typical features of middle ear structures in the gerbil are
      described.

PMID- 9198477
TI  - Characterization of V3 loop of HIV type 1 spreading rapidly among injection drug
      users of Manipur, India: a molecular epidemiological perspective.

PMID- 9198478
TI  - [Toxic megacolon].

PMID- 9198479
TI  - [Bibliographic errors in Revista Espanola de Enfermedades Digestivas. A
      retrospective study of the year 1995].
AB  - OBJECTIVE: To determine the accuracy of bibliographic citation in Revista
      Espanola de Enfermedades Digestivas (REED) and compare it with other Spanish and
      international journals. METHODS: We reviewed all 1995 volumes of the REED and
      randomly selected 100 references from these volumes. Nine citations of non
      journal articles were excluded and the remaining 91 citations were carefully
      scrutinized. Each original article was compared for author's name, title of
      article, name of journal, volume number, year of publication and pages. RESULTS:
      Some type of error was detected in 61.6% of the references and on 3 occasions
      (3.3%) impeded finding to the original article. Errors were found in authors
      (37.3%); article title (16.4%), pages (6.6%), journal title (4.4%), volume (2.2%)
      and year (1%). A single error was found in 42 citations, 2 were found in 13 and 3
      were found in 1. CONCLUSIONS: REED's rate of error in references is comparable to
      the rates of other spanish and international journals. Authors should exercise
      more care in preparing bibliographies and should invest more effort in
      verification of quoted references.

PMID- 9198480
TI  - [Nonepithelial malignant degeneration of esophageal duplication].
AB  - A communicating duplication of the distal esophagus was diagnosed in an elderly
      patient. The lesion was removed and the connection with the esophageal lumen
      closed. A high grade leiomyosarcoma involving all duplication layers and the
      right pleural surface was demonstrated. This is the first reported instance of a
      nonepithelial malignant tumor in an alimentary tract duplication.

PMID- 9198481
TI  - [Famciclovir plus interferon in the treatment of a patient with chronic hepatitis
      B and severe liver failure].
AB  - The natural history of liver disease caused by persistent infection with
      hepatitis B virus (HBV) can be quite variable. The wide range of liver injury
      suggests a great degree of variability in the interaction between the replicating
      virus and possible immune responses. At the current time, Interferon is the most
      extensively studied antiviral agent for chronic hepatitis B, but because of the
      substantial number of nonresponders, relapses and side events, it continues the
      search of alternative therapies. Many nucleoside analogues agents have been found
      to have antiviral activity in vitro or in vivo. The second generation nucleoside
      analogues with the most promising potential at present include Famciclovir. We
      report the case of a patient with HBV infection in whom a reactivation of his
      disease lead to hepatic failure, analysing the possible pathogenic mechanisms
      implied and calling attention upon the excellent results achieved with a combine
      regimen of Interferon and Famciclovir.

PMID- 9198482
TI  - [Large hepatic adenoma in a male patient].
AB  - Hepatic adenoma is a benign neoplasm found in women on oral contraceptives over
      long periods of time. Its incidence in men is lower, associated with androgen on
      anabolic steroid treatment, diabetes, storage diseases (glycogenosis type I and
      VI), barbiturates and clomiphene. We report a case of a man with a large hepatic
      adenoma without previous history of predisposing factors. The treatment was
      surgical because of the uncertain behaviour of this lesion.

PMID- 9198483
TI  - [Acute pancreatitis and malabsorption with tetany secondary to Crohn's disease
      with duodenal involvement].
AB  - Involvement of the duodenum in Crohn's disease is uncommon, and the
      pathomechanism of the associated acute pancreatitis remains controversial. We
      describe a case of Crohn's disease with duodenal involvement associated with
      hyperamylasemia and malabsorption showing a favorable response to steroid
      treatment.

PMID- 9198484
TI  - [Primary actinomycosis of the abdominal wall].

PMID- 9198485
TI  - [Cholestasis: an atypical presentation of portal cavernomatosis].

PMID- 9198486
TI  - [Krukenberg's tumor secondary to gastric neoplasms].

PMID- 9198487
TI  - [Pelvic lipomatosis as differential diagnosis of intestinal occlusion].

PMID- 9198488
TI  - Atrioventricular canal: introduction.

PMID- 9198489
TI  - Pankey and Tice receive 1996 IDSA Clinician Award.

PMID- 9198490
TI  - [Sacroiliitis:the key symptom of spondylarthropathies. 2: morphological aspects].
AB  - Because of their curved course and segmental convolution of articular surfaces,
      the anatomy of the sacroiliac joints is complex. An important part of the
      diagnosis of sacroiliitis of spondyloarthropathy patients relies on radiographic
      imaging techniques: x-ray, conventional tomography, computed tomography (CT) and
      scintigraphy. Diagnosis can be difficult in early and acute stages of
      sacroiliitis because radiographic findings may be normal, although dynamic
      magnetic resonance imaging (MRI) of the sacroiliac joints certainly enables to
      detect chronic as well as acute inflammatory changes. In spondyloarthropathy
      patients with acute sacroiliitis or acute exacerbation of chronic sacroiliitis
      who do not respond to or do not tolerate non-steroidal antiinflammatory drugs, CT
      guided corticosteroid injection into the sacroiliac joints has proved to be an
      effective therapy.

PMID- 9198492
TI  - [Fractal surface analysis of intrapulmonary space-occupying lesions from high
      resolution CT studies].
AB  - PURPOSE: The visual assessment of shape and surface structures of pulmonary
      nodules (PN) (smooth edges vs. spiculae) serves as a qualitative, subjective
      criterion in differential diagnosis. These properties must be quantified by
      computer-assisted evaluation, an adequate mathematical model, and new
      quantitative shape parameters. METHODS: 12 patients were investigated by high
      resolution CT. Based on 3D reconstructions with increasing thresholds, the PN
      surface S, volume V, fractal dimension (FD = In(S)/ In(square root of V)), and
      fractal index (F1 = square root of S/ square root of V) were calculated. RESULTS:
      The relations between the reconstruction threshold and the calculated tumour
      surface, respective volume, are of a fractal nature: S = c1 x thres1/d, V = c2 x
      thres1/D (c1, c2, d, D: real constants). Whereas the absolute values of surface
      and volume strongly depend on the chosen threshold (mean volume differences of
      249%), the derived parameter of the fractal dimension for a specific PN is nearly
      constant for all thresholds under review (r = 0.998, SD = 0.05). CONCLUSIONS: FD
      and FI are new diagnostic features for the assessment of PN surface structure and
      morphology. Thus, the assessment of pulmonary nodules can be supported by new
      quantitative parameters representing surface irregularity due to invasive tumour
      growth into adjacent tissue.

PMID- 9198491
TI  - [Results of a contrast-medium supported 3D MR-angiography in respiratory arrest
      following optimization of contrast medium bolus].
AB  - PURPOSE: Reduction of the contrast material volume by optimised bolus
      administration during a breath-hold 3D MR angiography and its clinical value.
      MATERIALS AND METHODS: Breath-hold ultrafast 3D gadolinium-enhanced MR
      angiography (TR 5 ms, TE 2 ms, FA 20 degrees) of the thoracic and abdominal aorta
      was performed in 50 patients and correlated with an i.a. DSA. 25 patients (group
      1) were examined with a contrast material volume of 40 ml Gd-DTPA and three
      successive acquisitions at fixed intervals (25, 53 and 81 s) after start of the
      contrast material injection. Another group of 25 patients (group 2) received only
      20 ml Gd-DTPA and the start of the MR acquisition was determined individually by
      prior evaluation of the contrast material transit times after injection of a test
      bolus. The signal-to-noise (S/N) and contrast-to-noise (C/N) ratios were compared
      and a subjective image quality rating (0-3) by three reviewers was achieved in
      both groups. RESULTS: A total of 37 vascular pathologies were correctly detected
      by MR angiography compared to i.a. DSA. The grading of stenoses was overestimated
      in some cases. The S/N and C/N were higher in group 2 (63.2 and 50.1) than in
      group 1 (58.0 and 38.9). The subjective ratings also showed better results in
      group 2 (2.76) than in group 1 (2.20). CONCLUSION: The ultrafast gadolinium
      enhanced 3D MR angiography allowed a reliable visualisation of the thoracic and
      abdominal aorta and its branches in a single breath-hold. An optimised
      examination with a reduced contrast material volume can be achieved by an
      individual adaptation of the MR acquisition to contrast material administration
      after measurement of the contrast material transit times.

PMID- 9198493
TI  - [Determination of cartilage thickness in the ankle joint. an MRT (1.5)-anatomical
      comparative study].
AB  - PURPOSE: The aim of this study was to evaluate the accuracy of MRI in the
      measurement of cartilage thickness of the ankle joint in comparison to pathologic
      and histologic specimens. PATIENTS AND METHODS: The ankle joints of four fresh
      cadaver feet were imaged on a 1.5T MR-unit in the coronal plane. Standard T1
      weighted spin echo (SE) and a T1-weighted 3D-GE (FLASH-3D) sequence with fat
      saturation were applied. Following MR imaging, the talus was explanted and cut
      parallel to the MR images for macroscopic evaluation and histologic specimens
      were prepared. MRI measurements of the cartilage thickness of the talus were
      carried out in two ways: without and with consideration of a transition zone of
      intermediate signal intensity between hyperintense cartilage and hypointense
      cortical bone. The data were compared with the anatomic specimens as the gold
      standard expressing the difference as a percentage value. On histologic specimens
      thickness of deep calcified cartilage layer was measured. RESULTS: Measurements
      without the transition zone showed a mean underestimation of talus cartilage
      thickness of 46.8% (41.3-52.1) for T1-SE and 47.5% (43.1-52.1) for fat saturated
      FLASH-3D images. Considering the transition zone the mean values were 25.0% (23.1
      26.2) and 14.1% (6.7-21.5). The histologic specimens showed a three-fold increase
      of thickness of deep calcified cartilage layer. CONCLUSIONS: Measurements of the
      cartilage layer of the ankle joint on MR images are only accurate if the
      transition zone (calcified cartilage layer) is considered and the optimal pulse
      sequence (FLASH-3D-fat-sat) is applied.

PMID- 9198494
TI  - [Osteoporotic stress fractures of the sacrum: MR-tomography findings].
AB  - PURPOSE: Evaluation of the morphologic appearance of sacral osteoporotic
      insufficiency fractures in MRI. PATIENTS AND METHOD: 6 patients (5 female and one
      male, 54-80 years) with osteoporotic insufficiency fractures of the sacrum were
      examined with CT and MRI. Plain and contrast-enhanced T1- and T2-weighted spin
      echo images were acquired, three patients were studied with T1-weighted gradient
      echo-sequences with fat suppression. RESULTS: Fracture-lines and sclerotic areas
      of the massae laterales were visible in 5 of 6 CT examinations, one patient
      showed no abnormalities of the sacrum on the initially performed CT scans. All
      patients had a diffuse bone marrow oedema of the fractured massae laterales with
      a decreased signal on the T1-weighted spin-echo images and an increased signal on
      the T1-weighted gradient-echo images with fat suppression and in the T2-weighted
      SE-sequences. Gadopentate dimeglumine enhanced MRI images showed a remarkable
      diffuse configurated high signal of the whole sacrum in bilateral fractures (H
      pattern). An additional soft tissue mass could be excluded in each case.
      CONCLUSION: Gadopentate dimeglumine enhanced MRI of sacral insufficiency
      fractures allows early diagnosis and helps to exclude intraosseous tumour
      formation.

PMID- 9198495
TI  - [Parametrial infiltration of cervix carcinoma: diagnostic value of contrast
      enhanced fat-suppressed T1-weighted SE sequences at 1.5 tesla].
AB  - PURPOSE: To determine whether contrast-enhanced and fat-suppressed sequences
      contribute to the MR imaging diagnosis of parametrial invasion. METHODS: 21
      patients with carcinoma of the cervix were prospectively examined with a phased
      array coil and a 1.5T MR-scanner using the following sequences: transverse T2
      weighted turbo spin echo (T2-TSE), T1-weighted spin echo (T1-SE) and fat
      suppressed T1-weighted SE sequences before and after Gd-DTPA. The sequences were
      evaluated separately for the presence of parametrial invasion. Image quality and
      diagnostic confidence were classified on a scale of 0-10 (nondiagnostic
      excellent). Findings were compared to the results of the pathohistological
      examination. RESULTS: Sensitivity, specificity and diagnostic accuracy were
      highest for T2-TSE sequences (100%, 79% and 86%, respectively). Contrast-enhanced
      T1-SE sequences with fat-suppression (71%, 79%, and 76%) showed no improvement
      compared to T2-TSE. Unenhanced fat-suppressed T1-SE (100%, 30%, and 56%) and
      unenhanced T1-SE (100%, 7%, and 38%) as well as contrast-enhanced T1-SE (86%,
      20%, and 47%) were significantly worse than T2-TSE. With similar image quality (p
      < 0.05) diagnostic confidence was higher on T2-TSE than on any of the other
      sequences (p < 0.001). CONCLUSION: Considering the cost-effectiveness of the
      examination, for the MR diagnosis of parametrial invasion the use of fat
      suppressed contrast-enhanced sequences can be abandoned in favour of T2-weighted
      TSE sequences.

PMID- 9198496
TI  - [Dynamic 31phosphorus magnetic resonance spectroscopy of the quadriceps muscle:
      metabolic changes under 2 different forms of loading].
AB  - PURPOSE: The aim of the present investigation was to examine the metabolism of
      the quadriceps muscles of normal young individuals using dynamic 31phosphorus
      magnetic resonance spectroscopy. METHODS: 22 normal individuals were examined in
      a 1.5T-MRT using a 6 cm surface coil. The metabolic changes in the quadriceps
      muscle as shown by the phosphorus spectrum were evaluated during rest, exercise
      (isometric and isotonic exercise) and during a 36-second period of recovery.
      RESULTS: The Pi/PCr quotient rose from its resting value of 0.11 +/- 0.02
      following exercise to a maximum of 0.83 +/- 0.47 (isometric) or 1.40 +/- 0.59
      (isotonic) (difference p = 0.0001). Half-time recovery of Pi/PCr was 35 +/- 11 s
      or 31 +/- 10 s, respectively (p = 0.13). During the recovery phase Pi/PCr fell
      briefly but significantly below its rest value. Following an initial rise in pH,
      there was a continual fall. Minimum pH (6.68 +/- 0.21 and 6.53 +/- 0.27
      respectively; p = 0.01) occurred in the early recovery phase. The recovery
      process of pH values lasted longer following isotonic than after isometric
      exercise (half-value recovery time 229 +/- 72 s and 146 +/- 55 s, respectively; p
      = 0.001). CONCLUSION: Compared with isometric exercise, isotonic stress is more
      expensive in terms of metabolism. Dynamic 31phosphorus MRT spectroscopy can
      differentiate changes in muscle metabolism during different forms of exercise.

PMID- 9198497
TI  - [Catheter visualization in MR-tomography: initial experimental results with field
      inhomogeneity catheters].
AB  - PURPOSE: To assess the feasibility of a new developed field inhomogeneity
      catheter for interventional MR imaging in vivo. MATERIALS AND METHODS: Three
      different prototypes of a field inhomogeneity catheter were investigated in 6
      pigs. The catheters were introduced in Seldinger technique via the femoral
      vessels over a guide wire on an interventional MR system (Philips Gyroscan NT
      combined with a C-arm fluoroscopy unit [Philips BV 212]). Catheters were placed
      in veins and arteries. The catheter position was controlled by a fast gradient
      echo sequence (Turbo Field Echo [TEE]). RESULTS: Catheters were introduced over a
      guide wire without complications in all cases. Using the field inhomogeneity
      concept, catheters were easily visualised in the inferior vena cava and the aorta
      by the fast gradient echo technique on MR in all cases. Although aortic branches
      were successfully cannulated, the catheters were not displayed by the TFE
      technique due to the complex and tortuous anatomy. All animals survived the
      experiments without complications. CONCLUSION: MR guided visualization of a field
      inhomogeneity catheter is a simple concept which can be realised on each MR
      scanner and may allow intravascular MR guided interventions in future.

PMID- 9198498
TI  - [Color-coded duplex ultrasonography of the orbit in central vein thrombosis].
AB  - PURPOSE: To evaluate the haemodynamic findings of orbital vessels in patients
      with central retinal vein occlusion by colour coded duplex sonography. METHODS:
      In 24 patients suffering from central retinal vein occlusion, confirmed by
      ophthalmoscopy and fluorescence angiography, colour-coded duplex sonography of
      central retinal vein, central retinal artery, posterior ciliary arteries and
      ophthalmic artery of the affected, and the unaffected contralateral eye, was
      performed and compared to a control group (150 healthy subjects). RESULTS: In
      eyes with central retinal vein occlusion, the maximum velocity of the central
      retinal vein was on average 4.55 cm/s (+/-2.37 cm/s) and, as compared with the
      unaffected eye (mean: 6.56 +/- 1.47 cm/s) and the control group (5.97 +/- 2.37
      cm/s), reduced significantly. In the affected eyes, the end diastolic velocity of
      the central retinal artery was reduced and the pulsatility index was increased
      significantly, compared with the unaffected eyes and the control group. Compared
      with the control group, the peak systolic and end diastolic velocities of the
      ophthalmic artery were significantly reduced. CONCLUSION: In conclusion, the
      findings assessed by colour-coded duplex sonography show a flow reduction in the
      central retinal vein and an increased arterial flow resistance in the retinal
      layer. There is good correlation with the angiographic results. Moreover, flow
      reductions in the ophthalmic artery, which are not seen in ophthalmological
      examinations, can be detected by this new examination technique.

PMID- 9198499
TI  - [Experimental validation of a semi-quantitative single-layer procedure for proton
      spin tomographic imaging of regional cerebral perfusion].
AB  - PURPOSE: The aim of the present study was to validate a simple MRI-procedure for
      semiquantitative assessment of regional cerebral blood flow. MATERIALS AND
      METHODS: Unilateral cerebral ischaemia (30 minutes) in the territory of the
      middle cerebral artery was induced in 14 anesthetised rates. The MRI-experiment
      consisted in an intravenous bolus injection of gadolinium-DTPA, recording of the
      cerebral contrast kinetics with a T2*-weighted pulse sequence, and measurement of
      the maximal concentration change at a chosen reference point of time. To measure
      perfusion quantitatively, a microsphere technique, an accepted reference
      technique was used. With both methods a perfusion index related to the
      contralateral side was calculated. RESULTS: In all cases decreased perfusion was
      detected by the MRI technique. The perfusion indices correlated with a
      coefficient of correlation of r = 0.89 (p < 0.001). CONCLUSION: The results
      demonstrate that contrast-enhanced MRI with bolus injection can be implemented
      with clinical potential as a semiquantitative instrument for the assessment of
      cerebral perfusion. Regional cerebral blood volume and collateral blood flow may
      interfere with the estimate of blood flow.

PMID- 9198500
TI  - [A new needle system for the MR-guided localization and transcutaneous biopsy of
      suspicious breast lesions. In vitro studies with 1.0 tesla].
AB  - PURPOSE: Examinations of a new needle system for localisation and core biopsies
      of suspicious breast lesions, detected by MRI alone, were performed. It was
      investigated whether this new needle system could reduce and avoid artifacts.
      MATERIAL AND METHODS: The new needle system was examined by Spin Echo Sequence
      and a Fast Gradient Echo Sequence on Magnetom Impact, 1.0 Tesla (in vitro
      examinations). The sizes of the coaxial needle system on the MR images were
      examined on various slice thicknesses and with several wires in this needle
      system. RESULTS: In the Spin Echo Sequence the measured size of the coaxial
      needle is the same as its real size. In the Fast Gradient Echo Sequence the
      measured size is about double that of the real size. CONCLUSION: The presented
      coaxial system will allow improved visualisation for both preoperative
      localisation and core biopsy.

PMID- 9198501
TI  - [Protective pneumothorax in CT-guided mediastinal puncture].
AB  - PURPOSE: To achieve an extrapulmonary pathway for biopsy of mediastinal masses.
      METHODS: In 6 patients a protective, temporary pneumothorax was established
      before performing large-bore needle biopsies of mediastinal masses using a Verres
      needle. RESULTS: Transpleural, extrapulmonary access was easy to achieve. One
      patient developed a tension pneumothorax after biopsy which was drained by
      percutaneous small chest tube. Another patient showed mediastinal tumor bleeding
      through the biopsy needle. As a prophylactic measure the bleeding was stopped by
      injection of tissue glue through the biopsy needle. CONCLUSION: The use of
      protective pneumothorax allows cutting needle biopsies of mediastinal masses
      where aspiration cytology yields no secure specific diagnosis.

PMID- 9198502
TI  - [Retroperitoneal bifocal ganglioneuroma--a case report].

PMID- 9198503
TI  - [Spiral computerized tomography and stereolithographic model planning exemplified
      by a mandibular osteosarcoma].

PMID- 9198504
TI  - [Jejunum stenosis as a late sequela of small-intestinal involvement in Wegener's
      granulomatosis].

PMID- 9198505
TI  - [Meningoencephalitis caused by Bacillus cereus].

PMID- 9198506
TI  - [Continuing education regulations].

PMID- 9198507
TI  - [Must the patient fast before intravascular injection of a non-ionic contrast
      medium? Results of a controlled study].
AB  - PURPOSE: Prospective evaluation of food and fluid restriction before the
      intravascular injection of a non-ionic contrast medium. MATERIAL AND METHODS:
      1000 patients (657 men, 343 women; average age 59 +/- 1/4 5 years) undergoing
      intravascular contrast injections (CT, phlebography, angiography, urography) were
      randomly allocated to two groups. Group A had no fluid or solids for at least
      four hours before the injection (499 cases); group B were allowed unlimited food
      and fluid (501 cases). Both groups were comparable in all other respects and all
      were given the non-ionic contrast medium iopamidol (300 mg l/ml). RESULTS: The
      incidence of acute complications was 3.5%. There was, however, no statistically
      significant difference between the two groups (p = 0.29). Late adverse reactions
      were seen in 3.9% patients. There was again no difference between the two groups
      (p = 0.33). No serious or life threatening complications occurred. CONCLUSION:
      Restriction of food and fluid before intravascular injection of contrast medium
      does not reduce the number of adverse side effects. For reasons of patient
      comfort and compliance, and to achieve adequate hydration, the patient should not
      fast before injection of contrast.

PMID- 9198508
TI  - [Analysis of reject x-ray films as a quality assurance element in diagnostic
      radiology].
AB  - PURPOSE: Analysis of reject films from a large radiological department under the
      following aspects: How big is the waste of films? Where are the sources of error?
      What are the possible means of quality assurance? MATERIAL AND METHOD: During a
      total period of 9 months, separated into three quarters, 14,570 reject films were
      analysed and assigned to 4 categories ("positioning", "exposure", "reject films
      due to patients" and "others"). In addition they were classified according to the
      respective parts of the body. The influence of a "study effect" was quantified by
      the analysis before and after information of staff. RESULTS: The reject film rate
      in relation to all performed x-rays, was 9.0-13.2% of all the films taken during
      that period: of these, the failure rate (x-rays useless for diagnosis because of
      their bad quality) was between 54.2 and 57.5%. In this category, the main sources
      of error were positioning (55%) and exposure (34%). Surprisingly, the technical
      film waste amounted to 42.5-45.8% (not developed or preexposed films, x-rays of
      phantoms etc.). CONCLUSION: Wasted films due to errors occurring during taking,
      as well as technical film waste, are unavoidable. Their proportion in relation to
      the total number of films should not exceed 8%. The main approach to reducing
      cost must be to cut down technical film waste.

PMID- 9198509
TI  - [Whole body spiral CT in primary diagnosis of patients with multiple trauma in
      emergency situations].
AB  - PURPOSE: The aim of this study was to evaluate the role of a fast whole body
      helical CT scanner for primary diagnosis in trauma patients. METHODS: 27 severely
      injured patients (9 women, 18 men; mean age 43 years) were first examined with a
      helical CT scanner allowing for digital radiograms up to a length of 1024 mm and
      continuous helical scans of up to 70 seconds (slice thickness 3 to 10 mm, pitch
      factor up to 2). The primary CT diagnosis was verified either by x-ray after the
      CT examination or during the subsequent days, by abdominal ultrasound, by
      additional CT scans in the following days, and by clinical follow-up. RESULTS: CT
      showed all clinically relevant injuries of the head, spine, chest, abdomen and
      pelvis. The diagnosis and classification of vertebral fractures was performed
      immediately. 4% of the fractures of the extremities and the ribs were not seen
      primarily. 6% of the injuries were outside the CT scan field. CONCLUSION: Helical
      CT is a reliable and fast method to obtain vital information and to improve
      management planning in severely injured patients. It reduces the number of
      conventional x-ray examinations. In certain cases, additional x-rays of extremity
      fractures may be required.

PMID- 9198510
TI  - [Follow-up of Crohn's disease: can hydro-MRI replace fractionated
      gastrointestinal passage examination?].
AB  - PURPOSE: To compare the value of hydro-MRI with follow-through examinations in
      the follow-up of Crohn's disease. METHOD: 22 patients known to be suffering from
      Crohn's disease were examined via 1.5 T-MR system; an oral contrast examination
      using 1000 ml of a 2.5% mannitol solution was performed in all patients. T2
      weighted TSE sequences and T1-weighted SE sequences were performed before and
      after the intravenous injection of Gd-DTPA. To reduce movement artifacts caused
      by peristalsis of the gut, intravenous injection of 40 mg Buscopan was given. The
      findings of hydro-MRI were compared with the follow-through examinations.
      RESULTS: In the upper gastrointestinal tract, the follow-through examination
      showed clear advantages compared with hydro-MRI for the demonstration of
      inflammatory changes in the gut; Hydro-MRI was, however, somewhat more reliable
      in the ileum and colon. It was also more sensitive than the follow-through for
      the demonstration of enteric fistulae (four as compared with two cases), and in
      demonstration extraluminal changes (free fluid in six against zero, and
      inflammatory adherent loops (four against zero)). Amongst the 22 patients, hydro
      MRI was equal (in 10) or better (in 8) than the follow-through examination for
      demonstrating the intestinal manifestations of Crohn's disease, and follow
      through was better in only four. CONCLUSION: For follow-up of Crohn's disease,
      hydro-MRI is at least as good as follow-through examination, and is even
      preferable, because of the absence of radiation exposure of the usually young
      patients.

PMID- 9198511
TI  - [Ultrafast contrast-enhanced 3D MR angiography of the aorta and renal arteries in
      apnea].
AB  - PURPOSE: To determine the value of ultrafast, gadolinium-enhanced, three
      dimensional breathhold magnetic resonance angiography (MRA) in the assessment of
      the aorta and renal arteries in comparison to conventional arteriography (CA).
      PATIENTS AND METHODS: 49 patients (31 m, 18 f) were evaluated with both CA and 3D
      MRA. The 3D MRA data set consisted of 44 continuous sections, acquired in apnoea
      (23-28 s) using the following parameters: TR/TE 3.9/1.5 ms, flip angle 40
      degrees, 3/4 k-space acquisition. 0.3 mmol/kg BW gadolinium-DTPA were
      administered intravenously in a bolus, using an automated injector. A test bolus
      method was used for timing of the bolus and beginning of the data acquisition.
      Intraarterial CA was used as the gold standard in 47 patients; in two patients
      the intraoperative findings were employed as the standard of reference. CA and
      MRA were interpreted separately by two different radiologists, who were blinded
      to the results of the other examiner. RESULTS: All 11 accessory renal arteries
      were visualised on MRA. MRA-based assessment of renal artery stenosis was
      identical with CA in 31 of 41 (75%) stenoses, Sensitivity and specificity values
      for assessment of renal arterial disease were 84.4% and 96.1%, for
      haemodynamically significant lesions they amounted to 90% and 98.9%,
      respectively. CONCLUSION: The presented ultrafast contrast-enhanced 3D MRA
      technique allows for the reliable assessment of aortic and renal arterial
      morphology and pathology.

PMID- 9198512
TI  - [In vitro study of morphology of the bladder wall using MR tomography at 1.0
      Tesla: correlation with histology].
AB  - PURPOSE: Evaluation of the potential of various MR techniques to differentiate
      bladder wall layers verified by histological findings. MATERIAL AND METHOD: 6
      bladder specimens of pigs were examined in vitro using T1-weighted spin-echo
      sequences, T2-weighted Turbo-SE, fat suppressed T2-weighted SE, and inversion
      recovery sequences. The MR images were obtained before and after fixating the
      specimens in formalin. Measurements of the thickness of bladder wall layers were
      performed on both sets of MR images as well as on histological sections, RESULTS:
      T2-weighted SE images showed three layers of different signal intensities: one
      innermost band of very high signal, one inner band of low and one outer band of
      intermediate signal corresponding histologically tunica propria and two different
      muscle layers. Inversion recovery technique provided similar findings but were
      able to avoid chemical-shift artifacts. After 24 hours in formalin, the signal
      intensity relation of the two muscle layers was inverted. The thickness of total
      bladder wall was not reduced significantly. Concerning the thickness of urinary
      bladder wall, histological measurements and evaluation of MR images correlated
      well. CONCLUSION: MR imaging enables the differentiation of three bladder wall
      layers. Inversion recovery technique achieved the best image quality by avoiding
      chemical shift artifact.

PMID- 9198513
TI  - [Contrast agent enhanced duplex ultrasonography: visualization of the hepatic
      artery after orthotopic liver transplantation].
AB  - PURPOSE: A prospective study was carried out to determine whether an improved
      assessment of the anatomy and flow velocity in the hepatic artery could be
      achieved by the administration of a capillary transversing contrast agent
      (Levovist) in patients after orthotopic liver transplantation. METHODS: In 21
      (62%) of 34 patients after liver transplantation, only an insufficient
      visualisation of the hepatic artery was achieved. Therefore, a capillary
      transversing contrast agent was administered intravenously. Pre- and post
      contrast peak velocity and Doppler frequency shift in the proper hepatic artery
      were measured and image quality of colour and spectral Doppler was assessed by a
      qualitative scale. RESULTS: Image quality, with complete visualisation of hepatic
      artery in 79% (precontrast 38%) of all cases, was significantly improved (p <
      0.01 (Wilcoxon test)) by the administration of a contrast agent. CONCLUSIONS:
      Visualisation of the hepatic artery after orthotopic liver transplantation can be
      improved by the administration of Levovist. It allows a reliable measurement of
      peak velocity and Doppler frequency shift and helps to avoid further imaging.

PMID- 9198515
TI  - [Artifacts in MR imaging of the temporomandibular joint caused by dental alloys:
      a phantom model study at T1.5].
AB  - PURPOSE: The influence of dental alloys on MRI of the temporomandibular joint was
      studied using a phantom model for this joint. METHODS: At 1,5 T, 15 dental alloys
      and 14 of their most important components were investigated acquiring sagittal
      (FOV: 150 mm) and transverse (FOV: 250 mm) T1-weighted SE images. In 11 cases, T1
      and T2*-weighted FLASH images were measured additionally. The artifacts were
      assessed qualitatively as well as quantitatively, and the samples were subdivided
      into four artifact categories. RESULTS: Ag, Cu, Ga, In, Tl, Sn, Zn, amalgam, the
      precious alloys, the Au-Pd and Ag-Pd alloys showed no artifacts (category I).
      Minimal artifacts below 10 mm on transverse images (category II) were found for
      Cr, Pd, Pt and for the Ni-Cr alloy. Mn and the remaining non-precious alloys
      induced artifacts up to 30 mm (category III). Significant artifacts-more than 30
      mm-(category IV) were caused by Ni-Cr and 18/8 wires and by Co, Fe, and Ni. T2*
      weighted FLASH proved to be more susceptible for artifacts than T1-weighted SE
      and FLASH techniques. CONCLUSIONS: In contrast to dental alloys for fixed
      prosthodontics, Ni-Cr- or 18/8 wires used for orthodontic bands can influence not
      only the image quality, but also the diagnostic reliability of MRI of the
      temporomandibular joint.

PMID- 9198514
TI  - [Interventional treatment of hemobilia].
AB  - PURPOSE: Aim of the study was to assess the use of embolisation in cases of
      iatrogenic haemobilia. METHOD: In 18 patients with severe haemobilia after
      percutaneous biliary system drainage or stent implantation, an embolisation with
      minicoils (17 x) or gelfoam particles, was performed. To achieve a sufficient
      vascular obstruction, Histoacryl (4 x) or Ethibloc (1 x) were additionally used
      in five cases. A transarterial approach was used in 17 cases. In one patient, an
      approach through the biliary system was possible. RESULTS: In all cases, the
      bleeding source was identified (5 false aneurysms, three biliary leaks, 9
      irregularities at the junction of the artery and drainage catheter, 1 multiple
      collaterals at the proximal end of the stent). In 17 out of 18 cases, haemorrhage
      ceased definitely. In one case of a patient with pancreas carcinoma and
      obstruction of the portal vein as well as a simultaneous high grade stenosis of
      the hepatic artery propria, it was only possible to embolise small collaterals to
      avoid liver necrosis. This resulted in an incomplete bleeding of control. An
      infected haematoma was the only complication. It was treated by drainage over 10
      days. During an observation period ranging approximately 7.6 months, 10 of the
      patients died due to their basic illness. CONCLUSION: Embolisation is an
      effective procedure in the treatment of haemobilia, with a low complication rate.

PMID- 9198516
TI  - [Comparison of different MRT techniques in the diagnosis of degenerative
      cartilage diseases. In vitro study of 50 joint specimens of the knee at T1.5].
AB  - PURPOSE: An experimental study was performed on joint specimens of the knee to
      assess the advantages and disadvantages of 14 generally available sequences in
      cartilage imaging. METHODS: Each of the 50 surgically exposed cadaveric joints of
      the knee was examined by the following sequences: T1, proton- and T2 weighted
      spin echo(SE) sequences, proton- and T2 weighted Turbo-SE, T1 weighted SE with
      fat suppression, MTC combined with T1-weighted SE and T2 weighted FLASH-2 D,
      STIR, FISP-3 D, FLASH-3 D (with fat suppression), and MR arthrography. We
      assessed the image quality by a scale, signal to noise-ratio of cartilage and
      joint fluid, and the accuracy in detection of cartilage lesions. Pathology and
      arthroscopy were reference methods to MRI, and demonstrated grade 1-4 lesions on
      186 of 300 joint facettes. RESULTS: Advanced stages of cartilage lesions (65
      grade 3 and 4 lesions) were detected by standard SE sequences in 67-94%.
      Application of volume techniques (FISP-3 D, FLASH-3 D), high definition matrix
      (512 pixel), MTC with FLASH-2 D and MR-arthrography improved the sensitivity up
      to 82-100%. Superficial lesions (65 grade 2 lesions) were demonstrated in 3-38%,
      and on MR arthrography in 45%. Structural changes (56 Grade 1 lesions) were
      recorded on MR) in only 10%. CONCLUSIONS: With regard to standard SE sequences,
      the detectability of cartilage lesions can be improved by techniques that use 512
      matrices, selective cartilage imaging, and volume acquisition.

PMID- 9198517
TI  - [Diagnosis and follow-up of muscle injuries by means of plain and contrast
      enhanced MRT: experimental and clinical studies].
AB  - PURPOSE: To clarify the value of plain and contrast-enhanced MRI for the
      diagnosis and follow-up of muscle injuries, by means of experimental and clinical
      studies. METHOD: 24 Wistar rats were studied following standardized division of
      the calf muscles by means of MRI carried out on the first day, and also after
      one, two, three and four weeks. In addition, 16 patients with muscle injuries
      were examined (32 examinations), first between the first and fifth day of trauma,
      and subsequently over a period of two to seven weeks (average: four weeks).
      RESULTS: In the animal experiments, there was signal reduction of T1 and an
      increase of the T2-weighted signal during the acute inflammatory phase. During
      the subacute reparative phase, there was an increase of both the T1-weighted and
      T2-weighted signals. These became reduced during the chronic healing phase. Early
      differentiation between intramuscular haematomas and bleeding, surrounding oedema
      and recognition of the divided muscle fibres was possible only after the
      intravenous injection of an MR contrast medium (Gd-DTPA). Suture of the divided
      muscles resulted in more rapid healing without major defects. CONCLUSION: It is
      possible to follow up the healing process after muscle injuries by means of plain
      MR. Contrast-enhanced MR allows early evaluation of muscle abnormalities, and is
      particularly valuable for recognising the margins of the injured muscles.

PMID- 9198518
TI  - [Radiological image of lobar holoprosencephaly: a rare development disorder of
      the embryonal prosencephalon].

PMID- 9198519
TI  - [Cystic adventitial degeneration of the popliteal artery].

PMID- 9198520
TI  - [Migration of an aneurysm clip in the ventricular system].

PMID- 9198521
TI  - [Gallbladder adenocarcinoma in villous adenomatosis (papillomatosis) of the
      gallbladder and common bile duct].

PMID- 9198522
TI  - Unilateral intermittent occlusion of a bicornuate uterus in association with
      ipsilateral renal agenesis and vena cava inferior duplication.

PMID- 9198523
TI  - [Liver hematomA and liver infarction: a severe complication of HELLP syndrome].

PMID- 9198524
TI  - Chronic non-malignant pain. Consider using opioids.

PMID- 9198525
TI  - Dermacase. Becker's nevus.

PMID- 9198527
TI  - [The similar capacity for self-maintenance of clonogenic hemopoietic cells (CFU-S
      11) from the liver and peripheral blood of sexually mature mice].
AB  - The capacity of CFU-S-11, which formed colonies in the spleen on day 11 after
      transplantation to an irradiated recipient for self-maintenance, was studied. The
      indices for self-renewal of individual CFU-S from the spleen, bone marrow, and
      peripheral blood were compared in the same sexually mature donor mice by
      retransplanting the colonies isolated from the spleen parenchyma to secondary
      recipients. The number of secondary CFU-S-11 per primary CFU-S-11 originating
      from the liver hardly differed from that originating from the peripheral blood,
      but is almost twice less than for the bone marrow CFU-S-11. The conclusion was
      drawn that compartment CFU-S of the liver of adult animals contains the cells
      migrating from blood flow, which, apparently, are not dormant embryonic cells.

PMID- 9198526
TI  - [Role models of residents graduating in family medicine and in different
      specialties in Quebec].
AB  - OBJECTIVE: To describe and compare the role models of Quebec residents graduating
      from French-language faculties of family medicine and from medical specialities.
      DESIGN: Survey by mail. PARTICIPANTS: Quebec residents graduating in family
      medicine (189), medical specialities (147), and surgical specialities (64) in
      1990. MAIN OUTCOME MEASURES: Number of models chosen, social, demographic,
      professional, and personal characteristics of primary role models, role models'
      influence on students. RESULTS: Role models chosen by family medicine graduates
      more closely resemble those of their medical speciality colleagues than those of
      their surgical speciality colleagues. Family medicine graduates, particularly
      female graduates, have more difficulty choosing models. Their choices are based
      mainly on qualities that reflect a biopsychosocial approach to care and concern
      with the community aspects of medical practice. CONCLUSION: Choosing role models
      is a complex process. Medical faculty in residency programs play an important
      role in the professional identity of future physicians.

PMID- 9198528
TI  - [The effect of thyroliberin on the structural characteristics of rat
      erythrocytes].
AB  - The effect of regulatory peptide thyrotropin-releasing hormone (TRH) on the
      structure of the plasma membrane and morphology of rat erythrocytes was studied
      using a spin probe and scanning electron microscopy. EPR spectra of the spin
      probe introduced in the intramembrane space demonstrate that TRH at 10(-7) and
      10(-3) M induces structural changes in the erythrocyte membrane. Scanning
      electron microscopy showed that introduction of TRH at 10(-11), 10(-7), and 10(
      3) M in the erythrocyte suspension increased the proportion of discocytes as
      compared to the control. This effect is due to TRH-induced cell transformation in
      discocytes. The obtained data suggest that TRH affects the membrane structure and
      the morphology of erythrocytes, changes the functional activity of these cells
      and, thus, indirectly influences the rate of the oxygen supply to tissue.

PMID- 9198529
TI  - [The mutation units of loci coding for lactate dehydrogenase and their directed
      changes in the phylogenetic progression of vertebrate animals].
AB  - Comparison of the electrophoretic mobility of various alleles of Ldh-A and B loci
      within and between species demonstrated a decreased range of variation from fish
      to anuran amphibians and from anurans to mammals. Fish and mammals feature
      incompatible ranges of this variation, usually having a mobility range above and
      below the first zone of Ldh-A and B loci heterodimers, respectively. Amphibians
      feature both types of variation. Such a quality difference in allelic variation
      may result from scaling down the amino acid changes from mutation of intragenic
      regions in fish to single amino acid substitutions in mammals.

PMID- 9198530
TI  - [The possible role of the elements of protein secondary structure in adaptation
      to the action of ionizing radiation].
AB  - Changes in the secondary structure of enzymes induced by gamma-rays 60Co at doses
      not exceeding one ionization per macromolecule were studied to elucidate a
      possible role of radiation-chemical processes in the evolution of proteins. The
      data on the comparative radioresistance of various types of secondary protein
      structures, alpha-helix, parallel and anti-parallel beta-structures, and beta
      turn, were obtained by the method of circular dichroism. It was shown that beta
      turns were resistant against radiation, alpha-helix was relatively stable, and
      beta-layer underwent significant changes. The importance of these structural
      types in the evolution of proteins is discussed. A special role of beta-turn as
      structural elements fixing the confirmation of macromolecules and therefore
      responsible for adaptation of the protein structure against a constant radiation
      background is proposed.

PMID- 9198531
TI  - [The protective effect of nitric oxide in heat shock].
AB  - Hyperproduction of the endogenous vasodilator nitric oxide (NO) is a main cause
      of arterial pressure during shocks of various origin. Here we show that the
      introduction of an exogenous NO donor, dinitrosyl iron complexes, reliably
      decreases mortality in rats due to heat shock from 57% to 8%. Simultaneously,
      dinitrosyl iron complexes prevent acute hypotension, excessive inhibition of
      vasoconstrictory, and enhancement of vasodilatory reactions related to NO
      hyperproduction. We propose that the protective effect of exogenous NO is due to
      inhibition of excessive synthesis of endogenous NO according to the negative
      feedback mechanism. Since dinitrosyl iron complex is a compound in which
      endogenous NO is deposited in the body under natural conditions, this NO donor is
      a promising means of prevention and therapy of pathological states related to
      both NO efficiency and hyperproduction.

PMID- 9198532
TI  - [Roles of vasoactive factors synthetized by endothelium in pulmonary arterial
      hypertension].
AB  - Pulmonary vascular endothelium synthesizes and releases two groups of vasoactive
      substances, namely the endothelium-derived relaxing and contracting factors.
      Among the former, the effects of nitric oxide (NO), formerly known as endothelium
      derived relaxing factor (EDRF), and those of the so-called endothelium-derived
      hyperpolarizing factor (EDHF) have been extensively investigated. Among the
      latter, endothelin is probably one of the most potent endogenous
      vasoconstrictors. NO is a free radical which can be readly inactivated by
      hemoglobin. NO has all the characteristics of a gas, whereas its pharmacological
      properties are consistent with those of an endogenous nitrovasodilator.
      Therefore, inhalation of the gas NO is now considered as one of the most
      promising means to treat persistent pulmonary hypertension of the newborn. EDHF
      relaxes vascular smooth muscle through activation of ATP-dependent potassium
      channels. Both the chemical nature and the physiological role of EDHF are still
      unclear. The pharmacological properties of endothelin are far from being
      unequivocal. It is a potent vasoconstrictor, when it directly acts on vascular
      smooth muscle. However, it can also induce the release of NO and EDHF, hence
      causing vasorelaxation. These effects of endothelin are mediated by various
      transduction pathways. Activations of ET-B receptors located on endothelium on
      the one hand, and ET-A receptors located on smooth muscle on the other hand, are
      responsible for relaxation and constriction of vascular smooth muscle,
      respectively. Such highly complex cellular mechanisms highlight the need for
      further insight into the physiology of the cell related to the pulmonary
      circulation. This, in turn, will help to better define the target upon which one
      can try to correct the abnormal function of the cell underlying the
      pathophysiological processes.

PMID- 9198533
TI  - [3rd National meeting of micturition disorders in children. Paris, 26-27
      September 1996. Proceedings].

PMID- 9198534
TI  - Proceedings of the VII International Symposium on Viral Hepatitis. Madrid, Spain,
      25-27 January 1996.

PMID- 9198536
TI  - Tobacco and aging: a call for papers for the global coordinated theme issues of
      1997.

PMID- 9198535
TI  - Denitration of 2,4,6-trinitrotoluene by Pseudomonas savastanoi.
AB  - Past disposal of wastewaters containing 2,4,6-trinitrotoluene (TNT) at the former
      Nebraska Ordnance Plant has resulted in numerous acres of TNT-contaminated soil.
      Examining the microbial population of these soils revealed several TNT-tolerant
      Pseudomonas spp. We selected one species, P. savastanoi, to determine its ability
      to transform TNT. Pure culture experiments were performed in pseudomonas minimal
      medium containing 0.31 mM TNT (70 mg TNT . L(-1)) under varied nutrient and cell
      density regimes. Experiments with TNT as a sole C or N source showed that P.
      savastanoi has the ability to denitrate TNT, as evidenced by production of 2,4
      dinitrotoluene (2,4-DNT) and NO2- with time. TNT denitration and formation of 2,4
      DNT were enhanced by removing NH4+ and adding NO2- to the growth medium. In all
      experiments, 2-amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene
      (4-ADNT) appeared as incidental reduction products. Glucose addition to the
      medium enhanced 2-ADNT and 4-ADNT production and decreased denitration of TNT.
      Mid-log phase cells rapidly transformed [ring-14C(U)]TNT but were unable to
      mineralize significant quantities of TNT, as evidenced by conversion of less than
      1% of the label to 14CO2. These results indicate that P. savastanoi is a TNT
      tolerant pseudomonad that can promote TNT degradation through reductive
      denitration and nitro moiety reduction.

PMID- 9198537
TI  - Smart polymers for fat reduction and drug absorption.

PMID- 9198538
TI  - The physical chemical basis for preserving cell structure for electron microscopy
      at the molecular level and available preparatory methods.
AB  - A method to prepare tissues for electron microscopy based on the kinetic theory
      of physical chemistry makes it possible to study the structure of cells at the
      molecular level because extensive denaturation of proteins is avoided in contrast
      to using conventional preparatory methods. The highly ordered arrangement of
      mitochondrial enzymes revealed by applying this method is discussed. Low
      temperature embedding, freeze-substitution, freeze-drying combined with low
      temperature embedding and freeze-fracturing are evaluated with respect to
      conditions for protein denaturation.

PMID- 9198539
TI  - Microbial biodegradation of organic wastes containing surfactants in a continuous
      flow reactor.
AB  - In a continuous flow bioreactor seeded with microbes from municipal activated
      sludge, complete organic carbon oxidation of simulated graywater (wastewater
      produced in human residences, excluding toilet wastes) was achieved at dilution
      rates up to 0.36 h-1 in the presence of 64.1 microM linear alkylbenzenesulfonate
      (LAS) L-1. At LAS concentrations of 187 microM, the system functioned only at
      dilution rates up to 0.23 h-1, and the biomass yield was two-fold lower. There
      were physiological changes in the microbial communities under different operating
      conditions, as measured by specific contents of ATP and extracellular hydrolases
      as well as the respiratory potential of the biomass. LAS inhibited the activity
      of LAS-degrading microbes at >150 microM LAS, and the activity of other microbes
      at >75 microM LAS. Chemical analysis of graywater indicated that samples
      consisted primarily of biological polymers (proteins and polysaccharides) and
      lower concentrations of surfactants. Biological remediation of graywater is
      possible, although treatment efficiency is influenced by the operating conditions
      and wastestream composition.

PMID- 9198541
TI  - Current readings in nuclear medicine.

PMID- 9198540
TI  - Control of the bronchial circulation. Proceedings of the da Vinci Society 4th
      International Meeting. 11-14 November 1996.

PMID- 9198542
TI  - [Surgical treatment for complicated clavicle fracture].
AB  - A review of 78 patients (43 males, 25 females), aged 17-62, operated on for
      complicated fracture of the clavicle served to present indications and surgical
      techniques for this treatment. The use of a metal plate allows for stable
      fixation of the fracture, thus further management of patients with concomitant
      thoracic, pulmonary, or spinal injuries does not require plaster cast
      immobilization. Inaccurate fracture fixation with compression screw as being
      unstable necessitates plaster cast immobilization. Coexisting shoulder
      dislocation has been primarily managed surgically.

PMID- 9198543
TI  - [Mikrozespol fixator in treatment of metacarpal malunion (preliminary report)].
AB  - Results of surgical treatment in 6 patients aged 21-40 (mean 30 years) with
      metacarpal malunion are presented. External version of Mikrozespol fixator has
      been used for stabilization of the fragments. Excellent radiographic result has
      been achieved in all cases. Functional assessment revealed 5 excellent and 1 good
      result. Bony union occurred after 7 weeks; complete function returned 5 weeks
      after surgery. The authors conclude, that Mikrozespol stabilization constitutes
      an alternative method for carpal malunion treatment.

PMID- 9198544
TI  - [Range of distal spondylodesis in surgical treatment of idiopathic scoliosis
      using multisegmental instrumentation].
AB  - This presentation aim was to provide correct answer in question of range of
      spondylodesis (both proximal and distal levels) in surgical treatment of
      idiopathic scoliosis with multisegmental instrumentation. The postoperative
      evaluation o 88 patients (77 girls and 11 boys) was done according to King and
      Moe classification. Average patients age was 13.8 years (11.4-17.1) with 18.2
      months (12-29) follow-up. In 53 cases it was longer than 2 years. The
      identification of the curve pattern in both the coronal and sagittal planes will
      allow you to decide which curves to fuse. In the choice of upper fusion level one
      should keep attention to shoulder balance and presence of superior junctional
      kyphosis, extending than range of the fusion up to T2. In the lower level there
      is important to keep distal fusion mass in vertical alignment transsected by CSL
      (just like in the upper end in thoracic spine) to preserve spine compensation and
      remaining as many sa possible mobile spine segments below the fusion.

PMID- 9198545
TI  - [Mineral changes in the intervertebral disc and facet joints during aging].
AB  - The mineralogic examinations of intervertebral disc and cartilages of facet
      joints, taken from corps of the accidents victims, from the level L4-L5, were
      performed. At the moment of accident the middle age of victim was 41.2 years (4
      87 years). Scanning microscopy, atom absorption, chemical analyses and electron
      microprobe analyses were used in the examinations. As the result of examinations
      we found: demineralisation of nucleus pulposus in the intervertebral disc and two
      kinds of mineralisation of anulus fibrosus--invisible and visible. Invisible
      mineralization was found as the initial stage of visible mineralization. In the
      cartilages of fact joints, similarly as in the anulus fibrosus, the visible
      mineralization was found, characterised by the presence of the different shaped
      mineral deposits in the microscope. The invisible mineralization characterised by
      increased content of Ca and P and by changes in the chemical composition of basic
      cartilage substance Fe, Cu, Pb, Zn, Sr, Na, K. It was detected with very
      sensitive methods. The very close relations between mineralogic changes in the
      intervertebral disc and facet joints cartilages were also found. Mineralogic
      changes in degenerative changes of vertebral column outstrip the radiologic ones.

PMID- 9198548
TI  - [Osteochondritis dissecans of the patella].
AB  - Symptoms and treatment of 16 years old patient who had osteochondritis dissecans
      of the patella is discussed. The separated cartilaginous fragment has been
      surgically removed, subchondral bone multiply drilled. After 3 months of
      exercises patient returned to the normal level of physical activity.

PMID- 9198547
TI  - [Cefamandole for perioperative prophylaxis in total hip alloplasty].
AB  - The aim of this paper was to present the use of Cefamandole as one of the
      elements in perioperative prophylactics in total hip replacement. One hundred
      patients operated between 1993 and 1995 were followed-up for mean 13.5 months.
      There were 33 males and 67 females, mean age was 61.4 years. Cefamandole was
      administered according to fixed protocol for three days (first dose along with
      premedication). Mono-antibiotic therapy was sufficient in most cases. No septic
      complication occurred, no side-effects of Cefamandole were recorded. The patients
      are still being followed-up. Results achieved resemble these from the literature
      so conclusion can be made, that Cefamandole is safe and efficient drug for peri
      operative prophylactics in total hip replacement.

PMID- 9198546
TI  - [Greater trochanter epiphyseodesis in treatment of hip deformity].
AB  - A series of 29 patients (33 hips) after greater trochanter epiphyseodesis in
      treatment for hip deformity has been reviewed. An indication for this surgery was
      increasing proximal femur deformity due to the damage of subcapital growth plate
      (avascular necrosis) during the treatment for congenital dysplasia of the hip.
      The age of patients at surgery was mean 8.1 years, mean follow-up was 10.1 year.
      Clinical and radiological assessment revealed ineffectiveness of greater
      trochanter epiphyseodesis in treatment for increasing hip deformity due to
      avascular necrosis in the age group in question.

PMID- 9198549
TI  - [Arthroscopic resection of bursitis changes in the pre-patellar bursae-
      preliminary report].
AB  - The author reports an arthroscopic method of excision of pre-patellar bursae
      employed in 6 cases. The etiology of bursitis was traumatic. Postoperative follow
      up averaged 4.5 months. The cosmetic effect of the endoscopic technique is
      superior to open surgery. No persistent tender scars and hypoesthesia about the
      scars were noted. All six cases did well. The recovery time was short. The
      economic advantages are obvious: reducing costs, saving time and shortening
      hospital stay.

PMID- 9198550
TI  - [New electromyographic test in orthopedic diagnosis. Part I].
AB  - The new electromyographic test is based on fast Fourier transformation
      application for analysis of global electromyograms. Specifically designed Dynalog
      apparatus is described. Dynalog records EMG signal and transfers it to IBM-PC.
      One hundred thirty-eight global electromyograms were taken from 4 muscle groups
      (m.rectus femoris, m.deltoideus, mm. flexores antebrachii, mm. extensores
      antebrachii) in healthy individuals. Standard graphs of power distribution were
      obtained. Physiologically, at maximum voluntary contraction, power distribution
      spectrum of 4 muscles display characteristic, repeatable features. The frequency
      distribution range is 0-250 Hz. The records obtained show an ascending part (10
      50 Hz), plateau (50-100 Hz) and mildly descending one at 150 Hz, subsequently to
      250 Hz.

PMID- 9198551
TI  - [Thoracic outlet syndrome].
AB  - Results of surgical treatment for thoracic outlet syndrome in 7 patients are
      reviewed. The symptom has been caused by cervical rib in 5 cases, in 1 case by
      the first rib anomaly and in 1 case by disturbed attachment of m.scalenus
      anterior. A case of misdiagnosed cervical rib is described in details; the
      patient has been operated on peripherally and serious iatrogenic complications
      followed. Ineffectiveness of pharmacotherapy and physiotherapy is pointed out.
      Surgical treatment resulted in remission of symptoms in 6 cases; in case of
      patient with iatrogenic complications marked improvement has been achieved. The
      aim of this paper is to demonstrate, that thoracic outlet syndrome promptly
      diagnosed and surgically treated has good prognosis.

PMID- 9198552
TI  - [Alendronate--a new drug for treatment of osteoporosis].
AB  - Bisphosphonates are new drugs in the therapy of osteoporosis. Till now, several
      drugs were described, among them alendronate. General features of bisphosphonates
      and some recent results of clinical trials are presented. The authors conclude,
      that alendronate is a well tolerated new treatment option reducing the risk and
      severity of new vertebral fractures, reducing the risk of nonvertebral fractures,
      and reducing the height loss.

PMID- 9198553
TI  - [Management of fractures in multiple injuries and multiple locations (instead of
      the discussion at the XXXI Congress PTOiTr)].

PMID- 9198554
TI  - [Transplantation law--quo vadis. Will current transplantation policy in Germany
      remain intact?].

PMID- 9198555
TI  - [Topic for discussion. Ambulatory appendectomy by the established surgeon].

PMID- 9198556
TI  - [Legal prohibition of professional rivalry and protection from competition in
      medical practice].

PMID- 9198557
TI  - [Principles of perioperative responsibility].

PMID- 9198558
TI  - [Revision of the brochure "Hygiene, Accident Prevention and First Aid" and
      "Recommendations for HIV-Post-Exposure Preventive Management].

PMID- 9198559
TI  - [Must the senior physician participate in emergency service by assistants?].

PMID- 9198560
TI  - [Staging laparoscopy].
AB  - The so-called extended diagnostic laparoscopy (EDL) facilitates the comprehensive
      exploration of the abdominal cavity, thus improving the precision of the
      pretherapeutic tumor staging in gastrointestinal malignancies. EDL comprises
      visual inspection with a specific preparation of all relevant sites, laparoscopic
      sonography and retrieval of samples for biopsy and cytology. Additional relevant
      therapeutic information was obtained through EDL in 40.5% of gastric cancer
      patients. EDL could be of similar importance for diagnosing esophageal,
      hepatobiliary and pancreatic malignancies.

PMID- 9198561
TI  - [Laparoscopic resections of malignant diseases of the gastrointestinal tract].
AB  - As the importance of laparoscopic surgery for benign diseases of the
      gastrointestinal tract continues to grow, the application of this approach in
      cases of malignancy remains controversial. Although the concept of cancer
      recurrence in the area of surgical wounds is not new, the incidence of port site
      recurrence is the most obvious concern. Indications and contraindications for
      surgery as well as a standardized nomenclature describing the type of
      laparoscopic procedures being performed are some other issues that need to be
      clarified. Complete laparoscopic procedures or the combination of laparoscopy
      with open techniques can offer advantages and disadvantages that surgeons will
      have to take into consideration when making decisions. The skill of the operating
      team and the extent of disease define the boundaries of laparoscopic surgery
      possible. The continued research as well as development of intelligent
      instruments and standardized techniques might give laparoscopy a clear role in
      the treatment of abdominal malignancies.

PMID- 9198562
TI  - [Errors and risks in oncologic laparoscopic surgery].
AB  - Oncological problems associated with laparoscopic colorectal surgery with
      curative intent include port site metastases, inadequate radicality, seeding of
      tumour cells through unprotected recovery of the surgical specimen, faulty
      surgical technique, and failure to observe the technical and/or oncological
      limitations applicable to certain tumour sites. Investigations so far reported
      reveal a preponderance of mechanical pathogenesis of port site metastases caused
      by the contamination of trocar entry ports by tumour cells borne on instruments,
      trocars and resected material. This suggests that appropriate precautionary
      measures could resolve the problem. It appears that the CO2 pneumoperitoneum
      plays only a minor role in the development of port site metastases. Owing to a
      lack of long-term data, the oncological radicality of laparosopic resections for
      colorectal carcinoma cannot be assessed; merely a few reports on the number of
      lymph nodes removed during such operations have been published. Nevertheless, it
      would appear that fewer lymph nodes were removed than with comparable
      conventional surgery. However, a more accurate analysis needs to take account of
      the fact that the indication for laparoscopic surgery is determined by the size
      and location of the tumour. The many potential pitfalls and hazards of
      oncological laparoscopic surgery make it mandatory that such interventions should
      be done only within the framework of prospective clinical studies covering
      limited indications. Randomized prospective studies to cover all tumour stages
      and sites cannot be recommended.

PMID- 9198563
TI  - [Minimally invasive surgery and tumor surgery--palliative laparoscopic
      techniques].
AB  - The oncological principles of radical tumor surgery are not proven to be
      successfully applied with today's laparoscopic techniques. The value of minimal
      invasive surgery has to be critically evaluated for the radical (R0) resection of
      malignant tumors. On the other hand, there is an indication for laparoscopic
      palliation in order to minimize the surgical trauma. Many publications have
      demonstrated the technical feasibility with acceptable morbidity and mortality
      and a decreased hospital stay. For different reasons (previous operations,
      assessment of resectability, use of interventional techniques etc.) laparoscopic
      palliation obviously is realized only in a small number of patients. The most
      frequently reported operation concerns the implantation of feeding catheters into
      the stomach or jejunum. If noncurability is proven preoperatively, the rate of
      laparoscopic palliations probably could be increased, if minimal access surgery
      could take a more definite place in the wide spectrum of therapeutical options.
      The operative techniques usually can be easily performed by the laparoscopically
      experienced surgeon today. However, benefit for the patients after palliative
      laparoscopic tumor resection has not yet been proven. The best condition for
      laparoscopic palliation is the discovery of the incurable situation during
      diagnostic laparoscopy. Laparoscopic palliation should follow directly within the
      same session.

PMID- 9198564
TI  - [Value of laparoscopic technique in primary colorectal carcinoma].
AB  - Patients who had undergone elective resection for primary colorectal cancer were
      included in a prospective study. The purpose of the study was to specify the
      current role of laparoscopic surgery in the treatment of colorectal cancer.
      Therefore, the reasons for performing the resection conventionally were
      documented under the general guideline that all colorectal cancer should be
      resected laparoscopically. Of 111 patients treated in 1995, only 22 underwent a
      laparoscopic resection and 4 patients a laparoscopic-assisted resection. Age, sex
      and tumor stage were comparable between groups. Operative time was longer in the
      laparoscopy group; duration of postoperative ileus and postoperative hospital
      stay were shorter. The most frequent indications for using a conventional
      approach were rectal cancer (n = 29), adhesions (n = 15), randomly selected
      patients (n = 14) and advanced cancer (n = 12). Cardiovascular risk factors were
      not so important. Laparoscopic techniques were only applied in a minority of
      patients with colorectal cancer (24-37%). Laparoscopic sphincter-preserving
      surgery is currently not recommended for rectal cancer in the middle and lower
      rectum. General risk factors are rarely a contraindication for a laparoscopic
      approach.

PMID- 9198565
TI  - [Laparoscopic cholecystectomy in therapy of acute cholecystitis: immediate versus
      interval operation].
AB  - From January 1991 to May 1996 a total of 3,010 cholecystectomies was performed
      for cholelithiasis. Pathohistologically an acute cholecystitis was found in 483
      patients (16%). The overall proportion of laparoscopic operations has increased
      from 12.5% in 1991 to 96.6% at present. In patients with acute cholecystitis the
      proportion of laparoscopic operations has increased from initially only 1.87% up
      to 83.3%. The duration of surgery (81 min versus 54 min), rate of conversion (12%
      versus 1.07%) and rate of complications (7.76% versus 2.2%) were all
      significantly higher in cases of acute cholecystitis than in those without
      inflammation. There was no mortality in either group. Furthermore no significant
      difference was found between patients with histopathologically proven acute
      inflammation and patients with an acute episode of chronic cholecystitis. The
      duration of complaints, however, had a significant influence on surgical results.
      In patients that were either operated on within 48 h after the onset of disease
      or more than 10 days later, the length of the operation was shorter and the rates
      of conversion and complications were lower. Our results prove that laparoscopic
      cholecystectomy is also very successful in cases of acute cholecystitis, though a
      long learning curve has to be expected. Taking efficiency and economy into
      consideration, surgery within a few days of the onset of disease must be
      recommended.

PMID- 9198566
TI  - [Laparoscopically placed clips on the human cystic duct--an experimental
      comparison of dislocation between resorbable and titanium clips].
AB  - Kryopreserved specimens of cystic ducts were used for displacement tests to
      investigate the security of different laparoscopic clips. The cystic duct was
      fixed, and the transverse placed clips were distracted in axial direction and the
      forces registered. The median values of the six investigated clips ranged between
      4.1 N and 11.2 N with a highly significant difference (P < 0.001, Kruskal-Wallis
      ANOVA). In detail, both resorbable clips (polydioxanone, polyglyconate/polyglycol
      acetate) were superior to the four titanium clips (P < 0.005, Wilcoxon test). In
      addition to the advantage of complete biodegradibility, these data favour the use
      of absorbable clips because holding force is better than that of titanium clips.

PMID- 9198567
TI  - [Repeat interventions in metastases].
AB  - Between 1985 and 1994, 262 patients with metastases underwent resectional
      treatment in the Department for General and Abdominal Surgery of the University
      of Mainz. Twenty-seven patients with recurrent metastases were treated with
      repeat resections. The records of these 27 patients were reviewed and analyzed.
      After 42 repeat resections, 4 of 27 patients (14.8%) developed complications.
      Three of 27 patients died in the postoperative period (11.1%). For patients with
      R0 resection of metastases from colorectal primaries the median survival time was
      69 months after resection of the primary tumor (n = 16), 38 months after the
      first resection of metastases (n = 15), and 25 months after the second resection
      of metastases (n = 15). After the last repeat resection of metastases in each
      patient, median survival was 25 months in patients with R0 resection (n = 11),
      compared to 7 months following R1/2 resection (n = 5) (P = 0.007). Disease-free
      survival following first R0 resection of colorectal metastases (n = 15), was not
      significantly different from disease-free survival following repeated R0
      resection of colorectal metastases (n = 21). Patients with repeat resection of
      colorectal liver metastases (n = 9) had longer disease-free survival (median 18
      months) than patients with repeat resection of colorectal metastases in organs
      other than liver or lungs (median 4 months; n = 4) (P = 0.005). Repeat resections
      for metastases are characterized by low operative risk and a prognostic benefit
      for highly selected patients.

PMID- 9198568
TI  - [Recurrent pneumothorax after surgical resection treatment].
AB  - Between 1984 and 1994, 27 men and 4 women with primary spontaneous pneumothorax
      were treated surgically by excision of the bullae, without pleurectomy. The
      purpose of the present study was to establish by computed tomography (CT) of the
      lung whether the excision permanently eliminated the cause of pneumothorax. The
      median follow-up was 72 (21-127) months. There were two patients with recurrences
      (6.4%) who were operated on again. Sixteen of 31 patients had new blebs in the
      apex of the lung as documented by postoperative CT. The study indicates that
      simple excision of the bullous area cannot prevent the recurrence of blebs.

PMID- 9198570
TI  - [Effectiveness of alcoholic hand disinfectants against methicillin resistant
      Staphylococcus aureus].
AB  - In order to determine the efficacy of hand disinfectants based on alcohol against
      three MRSA strains and 3 methicillin-susceptible S. aureus strains (MSSA), 1
      propanol (60%) as well as Sterillium and Spitaderm were investigated in the
      quantitative suspension test at various dilutions and reactions times (15, 30 and
      60s). All undiluted disinfectants revealed reduction factors > 6 against MRSA and
      MSSA after 30s. Diluted disinfectants (50%) were significantly less effective
      against MRSA at short reaction times (15 s) (p < 0.05). Sterillium in a dilution
      of 50% did not reach 5 reduction factors against either MRSA or MSSA after 30 s.
      The impact of an appropriate use of hand disinfectants in order to break chains
      of infections with MRSA is obvious.

PMID- 9198569
TI  - ["Tension-free technique" in open inguinal hernia repair. A prospective,
      randomized study of postoperative pain perception ("tension-free reconstruction"
      vs. Shouldice technique)].
AB  - A prospective randomized study was performed on 64 patients suffering from
      primary inguinal hernia. Two groups were formed, each consisting of 32 patients.
      The patients either underwent tension-free surgical treatment or Shouldice
      herniorraphy. The aim of the study was to determine if the tension-free operative
      technique on inguinal hernia patients reduces postoperative pain intensity by 2
      days in comparison to the patients receiving Shouldice repair treatment. By using
      the VAS was shown that at no time was there any significant difference in the
      pain sensation levels between the two groups. The amount of pain tablets consumed
      among the patients was similar in each group. The number of complications in both
      groups was also comparable. During the postoperative follow-up of 6 days six
      patients in the tension-free surgical group and four patients in the Shouldice
      group developed uncomplicated hematomas on the 4th day, which were traced to the
      heparin medication. One patient from the Shouldice group suffered from temporary
      swelling of the scrotum. The advantage of open tension-free repair using
      extraperitoneally placed polypropylene mesh is that the technique is simple, size
      adapted, and can be carried out easily and at any time under local anesthesia.
      With regard to the lower recurrence rate of hernia as published in the American
      literature, this can only be verified by randomized studies.

PMID- 9198571
TI  - [Laparoscopic colon reposition and closure of the diaphragm in secondary
      incarcerated pre-existent diaphragmatic hernia].
AB  - We report on a 28-year-old patient, who acquired a left diaphragmatic hernia
      after suffering a motorcycle accident seven years ago. The diaphragmatic hernia
      was not diagnosed at that time. After a laparoscopic cholecystectomy performed
      for acute cholcystitis, there was herniation and secondary incarceration of a
      bowel segment into the preexistent diaphragmatic hernia. We describe laparoscopic
      surgical repositioning of the bowel segment and closure of the diaphragmatic
      defect.

PMID- 9198572
TI  - [Distal perforation of the small intestine by PEG endpiece in an inguinal hernia
      patient].
AB  - The PEG-ileus is a complication of the intestinal migration of the "bumper". The
      resulting obstruction or perforation is usually located in the ileum. Patients
      with hernias, who have a possible or known intrinsic or extrinsic stenosis or who
      have been X-rayed in the area of the small pelvis, are not suitable for the
      application of Korula's "migration"-technique with the scheduled intestinal
      elimination of the "bumper". "Bumpers" that are allowed to remain in the stomach
      for a long time lose their elasticity and frequently cause a PEG-ileus. When
      choosing the type of gastrostomy, we should consider which technique could be
      used in the case of a change or a removal of the material.

PMID- 9198573
TI  - [Madelung disease. A case report with special reference to therapy].
AB  - Madelung-Launois-Bensaude lipomatosis is a rare disease characterized by an
      enormous accumulation of fat, mainly in the region of the neck. A case is
      presented to illustrate the course of the disease and its clinical features. In
      particular, the necessity for a bilateral conservative neck dissection is
      emphasized to avoid early recurrence.

PMID- 9198574
TI  - [Infiltrating intramuscular lipoma].
AB  - Intramuscular lipomas are rare, benign unencapsulated tumors. They are also
      called infiltrating lipomas because of their infiltrative growth pattern which,
      deeply localized, seizes the skeleton muscle. The only obvious symptom is a
      palpable mass. Microscopically, monovacular fat tissue shows up between the
      muscle fiber. In extreme cases the preexisting muscle can be totally replaced by
      fat tissue. A precise pathohistological examination is needed to avoid the
      mistaken diagnosis of a well-differentiated liposarcoma. Late diagnosis, the
      extent and the localization of the tumor often do not allow for an R0 resection
      and influence the postoperative recurrence rates, which lie between 3 and 62%. R0
      resections are not desirable when postoperative severe loss of function can be
      expected. Malfunctions will slowly take place and can greatly be compensated, in
      contrast to a radical procedure with immediate loss of function.

PMID- 9198575
TI  - The molecular basis of cellular defense mechanisms. Symposium proceedings.
      Melbourne, 19-21 March 1996.

PMID- 9198576
TI  - World food summit.

PMID- 9198577
TI  - Communicating risk in a changing world.

PMID- 9198578
TI  - Planes and pollution.

PMID- 9198579
TI  - Failure of in vivo labelling of erythrocytes with technetium-99m: it is not
      Teflon that is the problem but rather the injection technique.

PMID- 9198580
TI  - Imaging of dopamine transporters in humans with technetium-99m TRODAT-1.

PMID- 9198582
TI  - Fertility and Sterility continuing medical education questions.

PMID- 9198581
TI  - Measurement of the radioactive body burden in patients receiving iodine-131
      treatment for carcinoma of the thyroid.

PMID- 9198583
TI  - Proceedings of the 9th Symposium on Signals and Signal Processing in the Immune
      System. Tihany, Hungary, September 8-12, 1996.

PMID- 9198584
TI  - In vitro study on the effect of larval excretory/secretory products and crude
      extracts from Anisakis simplex on blood coagulation.
AB  - The anticoagulant action of Anisakis simplex larvae on human blood in vitro was
      examined. Anticoagulant activity was assessed by routine screening tests that
      evaluate the overall competency of the coagulant mechanism. A slight prolongation
      of the prothrombin time (PT) was observed with the larval crude extracts.
      Prolongation of the PT was seen at a concentration of excretory/secretory (ES)
      products greater than 62.5 micrograms/ml. No prolongation of the activated
      partial thromboplastin time (PTT) was observed using crude extracts. There was a
      prolongation of the PTT with ES products at concentrations greater than 62.5
      micrograms/ml. ES products of the larvae were able to prolong coagulation times
      indicating that they contain an inhibitory or anticoagulant property. Preparation
      of crude extracts of A. simplex showed only minimal anticoagulant activity. The
      results obtained by measurements of the PT and the PTT suggest a probable
      alteration of one of the coagulation proteins namely factors Xa, IIa or Va. These
      findings suggest that the anticoagulant activity demonstrated in the ES products
      may play an important role during invasion of the gastric or intestinal mucosa by
      larvae and could have biological significance in infected patients.

PMID- 9198585
TI  - The developmental expression of cysteine proteinases in Schistosoma mansoni.
AB  - In this study several probes were used to identify and characterize cysteine
      proteinases (CP) from Schistosoma mansoni developmental stages. Proteinase
      activity was detected in all developmental stages using fluorogenic substrates.
      Specific activity was 4- to 11-fold higher against CBZ-phe-arg-AFC than against
      CBZ-arg-arg-AFC. A 32 kDa S. mansoni CP (Sm32) was identified in all stages by
      the radiolabelled active site CP inhibitor, CBZ-[125I]tyr-ala-CHN2. A second CP,
      of 31 kDa (Sm31) was only detected in adult worms, primarily female worms and
      late schistosomula. Monoclonal antibodies for Sm32 and Sm31 reacted with
      homologous CP only in adult worms and late schistosomula. This study defines the
      developmental expression of CP activity in S. mansoni.

PMID- 9198586
TI  - Trypanosome-binding proteins of the tsetse flies Glossina palpalis gambiensis and
      G. morsitans morsitans.
AB  - In this paper we describe a new, selective approach to identify protein ligand
      receptor interactions between an arthropod vector and the parasite it transmits.
      Biotinylated vector proteins were incubated with living parasites in
      physiological conditions. After extensive washing, the parasites were subjected
      to SDS-PAGE electrophoresis and the polypeptides were electroblotted onto
      nitrocellulose membrane. Staining with avidin-horseradish peroxidase revealed
      only biotin-labeled proteins from the vector which were bound to the parasite. A
      multitude of tissue-specific proteins of Glossina palpalis gambiensis and G.
      morsitans morsitans proteins, able to bind to cultured procyclic trypanosomes of
      Trypanosoma brucei spp., has been demonstrated. The relevance of these
      interactions in relation to the developmental journey of the trypanosome in the
      tsetse fly is briefly discussed.

PMID- 9198587
TI  - The effects of bistratene A on the development of Plasmodium falciparum in
      culture.
AB  - The effects of the marine ascidian compound bistratene A on in vitro cultures of
      Plasmodium falciparum were assessed. Concentrations from 0 to 1.5 micrograms ml(
      1) of the compound were tested. The parasitaemia in asynchronous cultures treated
      with bistratene A increased normally over the first 40 h, then decreased leaving
      only gametocytes. When synchronized cultures were treated with a constant dose of
      50 ng ml(-1), gametocytes developed more rapidly than they did in control
      cultures. In addition, gametocytes developed in drug-treated cultures of P.
      falciparum that normally do not produce gametocytes. Bistratene A appears to
      inhibit merozoite invasion as well as to induce gametocytogenesis.

PMID- 9198588
TI  - The value of circulating eosinophil count as a selection criteria for resistance
      of sheep to trichostrongyle parasites.
AB  - In merino sheep bred for either increased or decreased resistance to Haemonchus
      contortus, faecal worm egg counts (FEC) were lower in the resistant line (6,831
      vs 17,645 epg, P < 0.01), and circulating eosinophils (EOS) were higher, but not
      significantly so (3.40 x 10(4) ml(-1) vs 1.40 x 10(4) ml(-1), P = 0.1 1). Another
      flock was artificially infected with Trichostrongylus colubriformis and
      significant genetic variation was found in both FEC (heritability 0.40 +/- 0.11)
      and EOS (0.19 +/- 0.08). In a third flock comprising tropical sheep breeds, a
      natural challenge with T. colubriformis resulted in significant sire effects on
      FEC (heritability 0.20 +/- 0.10) but not EOS (heritability inestimable). We
      conclude that EOS offers no advantage over FEC as it selection criterion for
      resistance.

PMID- 9198589
TI  - Dot-immunogold-silver staining in the diagnosis of cysticercosis.
AB  - Dot-immunogold-silver staining (Dot-IGSS) and Dot-ELISA were used, with Taenia
      solium cyst fluid antigen, to detect specific antibodies in the sera of patients
      with cysticercosis. All 40 confirmed cases of cysticercosis were found to be
      positive when tested by 2 methods. The average titer of the sera detected by Dot
      IGSS was 1:27,470, which was significantly higher than that detected by Dot
      ELISA. The false positive rates were 2% and 4% in 50 healthy controls for Dot
      IGSS and Dot-ELISA, respectively, with a low titer of 1:20.

PMID- 9198590
TI  - Demonstration of common and stage-specific anti-Hepatozoon mocassini antibodies
      in experimentally infected unnatural lizard hosts.
AB  - This study examines the immunological response to Hepatozoon mocassini in
      lizards. Three lizard species were infected experimentally with H. mocassini.
      Baseline and post-infection (PI) sera were assayed for anti-H. mocassini meront
      and gametocyte antibody by immunohistochemistry and IFA. Seroconversion occurred
      at 38 d PI with endpoint IFA titers of 1:64. Antisera from non-parasitaemic and
      parisitaemic lizards exhibited similar affinities for merozite and gametocyte
      antigens. Antibody specific for the membranes of gametocyte-infected erythrocytes
      was demonstrated exclusively in parasitaemic lizards. The results demonstrate
      that lizards infected with snake haemogregarines mount an antibody response with
      common and stage-specific components.

PMID- 9198591
TI  - In praise of pioneers.

PMID- 9198592
TI  - Biliary tract cryptosporidiosis immunosuppressed rat model.
AB  - Rats immunosuppressed by hydrocortisone acetate and a low protein diet were
      challenged with Cryptosporidium Parvum oocysts and studied on days 10, 35 and 70
      post-infection. The biliary tract was found to be a major site of parasite
      infection. C. parvum was visible in the biliary papillary area in association
      with a proliferation of highly convoluted tubular glands. The papillary lumen was
      narrowed, and an upstream dilation with bacterial proliferation was seen. The
      liver was initially free of lesions, and subsequently exhibited late lesions of
      cholestasis. Parasites were not found in the pancreatic duct, although
      pancreatitis was frequently observed. Oocysts were consistently present in the
      distal portion of the ileum. Both challenged and unchallenged immunosuppressed
      rats, exhibited widespread focal hepatic infarcts and pyelonephritis. Other
      organs appeared free of lesions. In addition to the intestine, data identified
      the biliary tract as a major site of C. parvum infection and as a potential
      protected reservoir which may sustain a chronic infection.

PMID- 9198594
TI  - A comparison of the adult and miracidial stages of Echinostoma paraensei and E.
      caproni.
AB  - Adult Echinostoma paraensei and Echinostoma caproni were grown in outbred mice
      and golden hamsters to compare size, growth rates, infectivity, and habitat
      selection. Antagonistic responses between the 2 species were investigated by
      concurrent infections in mice. Miracidial stages were compared for developmental
      stages, hatching responses, and behaviour to light and gravity. Size differences
      and growth rates were significantly different in both mice and hamsters. Mice
      proved to be better hosts for E. caproni and hamsters for E. paraensei. In mature
      infections, E. paraensei adults localized in the duodenum and E. caproni in the
      ileum of both mice and hamsters. In concurrent infections of mice, E. paraensei
      adults were significantly smaller than in single species infections beyond 14
      days post-infection, while E. caproni adults were either equal to or larger than
      those in single species infections. On the other hand, E. paraensei were
      recovered in larger numbers in concurrent infections than in single species
      infections, while the reverse was found for infectivity of E. caproni adults.
      Miracidia of E. paraensei developed at the same rate as those of E. caproni in
      both light and dark cultures, but E. paraensei hatched much sooner when exposed
      to light. No miracidia hatched from cultures kept in the dark, indicating light
      is needed to stimulate the hatching process. All light-stimulated cultures
      exhibited a circadian hatching pattern from 1100 to 1600 hours. Cultures
      maintained in the dark past 11 days did not hatch when exposed to light.
      Miracidia of E. paraensei showed a positive phototaxis but no response to
      gravity. This comparison of life cycle stages leads us to conclude that E.
      paraensei and E. caproni are distinct species.

PMID- 9198593
TI  - Influence of organic acid excretion on cuticle pH and drug absorption by
      Haemonchus contortus.
AB  - To determine if a cuticle microenvironment pH is maintained by adult Haemonchus
      contortus, organic acid excretion kinetics and absorption kinetics of selected
      model weak acids and a weak base were measured in incubation media that varied in
      buffer capacity (0.25-20 mM HEPES or 5 mM glycine) and initial pH (7.5 or 3.5).
      To evaluate the importance of the cuticle as a pathway for organic acid excretion
      and drug absorption the pharynx was paralyzed with 1 nM ivermectin. H. contortus
      changed the media pH from initial values of 7.5 or 3.25 to an asymptotic value of
      approximately 5.6. The rate of pH change depended on the buffer capacity, but was
      not affected by chemical ligation with ivermectin. The intrinsic rate of
      excretion of organic acids (0.045 +/- 0.016 micromol/cm2 x h) was constant during
      the first 8-12 h of incubation and was independent of initial pH, buffer capacity
      or ivermectin ligation. The rates of absorption of the model weak acids, benzoic
      acid and p-nitrophenol, and the model weak base, aniline, were not affected by
      initial pH, buffer capacity or ivermectin ligation. These results suggest that H.
      contortus excretes organic acid endproducts of carbohydrate metabolism across its
      cuticle, and that these acids maintain a microenvironment pH within the water
      filled pores of the cuticle that controls the rate of adsorption of weakly acidic
      or basic drugs.

PMID- 9198595
TI  - Experimental studies on the pathway for migration and the development of Taiwan
      Taenia in domestic pigs.
AB  - The pig is the most favorable experimental intermediate host of Taiwan Taenia.
      Cysticerci in infected pigs are located in the liver except for a few
      extrahepatic ones. The present study was designed to investigate the pathway of
      migration of the oncospheres of Taiwan Taenia in the pig. In the first group,
      each of 5 Small-Ear-Miniature (SEM) and one Landrace-Small-Ear-Miniature (L-SEM)
      pigs were injected with 5000 hatched oncospheres into the ear vein. Three SEM and
      one L-SEM pigs were found to harbor 88 degenerated or calcified cysticerci only
      in the liver 51-81 days after injection. In the second group, each of 3 L-SEM
      pigs were injected with 5000 hatched oncospheres into the jugular vein. One of
      the 3 pigs was found to have 5 cysticerci (2 mature and 3 degenerated or
      calcified) only in the liver at 89 days post-injection. In the third group, each
      of 4 SEM, three L-SEM, and 3 L-SEM pigs were injected with 10,000, 10,000, and
      5000 hatched oncospheres, respectively, directly into the portal vein after
      surgical opening of the abdominal cavity. All 10 pigs were found to be infected
      with a total of 1088 cysticerci (44 mature and 1044 degenerated or calcified)
      only in the liver 23-62 days after injection. Although the sites of injection in
      these three groups were different, the liver was the only final location of the
      cysticerci. These findings give strong evidence that the oncospheres migrate to
      the liver through the venous circulation and develop in this organ.

PMID- 9198596
TI  - The effects of closantel treatment on the ultrastructure of Haemonchus contortus.
AB  - H. contortus were recovered from sheep 0-14 h after intramuscular treatment with
      closantel. Ultrastructural examination revealed that mitochondria were more
      electron dense and contained swollen cristae compared with untreated controls.
      Following treatment, the basal channels in the intestine became prominent and
      there was vesicle formation in all organs examined. In contrast, closantel
      resistant H. contortus appeared normal after drug treatment. It is likely that
      closantel affects membrane associated processes responsible for fluid and ion
      homeostasis as well as mitochondrial function. Untreated H. contortus were
      maintained in balanced salt solution for 12 h which caused lesions indicative of
      fluid imbalance, but at 23 h there were serious structural abnormalities.

PMID- 9198597
TI  - Development of chemotherapeutic model for the in vitro screening of drugs against
      Echinoccus granulosus cysts: the effects of an albendazole-albendazole sulphoxide
      combination.
AB  - This paper describes a novel experimental model for the screening of putative
      drugs against the metacestode stage of E. granulosus using hydatid cysts derived
      from in vitro culture of protoscoleces. The effects of an ABZ+ABZ.SO combination
      against cultured and murine cysts were studied with this in vitro model system.
      This treatment produced loss of turgidity of the cultured cysts in less time than
      in the murine cysts but the ultrastructural tissue damage observed in both
      cultured and murine cysts was similar. The ultrastructural changes induced by
      ABZ+ABZ.SO were: (i) vacuolation of the distal cytoplasm that extended to the
      tegumentary cells of the germinal membrane; (ii) increased number of
      mitochondria; (iii) partial loss of microtriches; (iv) increased number of
      autophagosomes; and (v) an increase in lipid deposits.

PMID- 9198598
TI  - Bulk-freezing of Theileria parva stabilates for vaccine production.
AB  - The freezing and thawing characteristics of different volume samples of freezing
      medium and Theileria parva stabilates were studied in order to identify suitable
      conditions for freezing large volumes of stabilates for use in the preparation of
      vaccines. Conventionally, 1.8 ml aliquots are used but are cumbersome to handle
      in the field preparation of trivalent vaccines. In this study, 75 ml aliquots of
      the stabilates were found to exhibit freezing and thawing characteristics similar
      to those of the 1.8 ml aliquots. Bulk freezing of 2 stabilates yielded
      sporozoites which remained infective for cattle upon thawing, induced a range of
      clinical reactions in vaccinated cattle and stimulated the development of immune
      reactions.

PMID- 9198599
TI  - Finding genetic markers for complex phenotypic traits in parasites.
AB  - The identification, mapping and eventual cloning of genes which determine or
      influence important epidemiological traits in parasites can have great benefits
      for the control of parasitic disease. In this review, strategies are outlined for
      identifying genetic markers for complex, quantitative traits. A genetic marker is
      a variable DNA sequence which co-occurs with a variable quantitative trait.
      Candidate markers are chosen because they are thought to directly influence the
      trait whereas random markers are expected to be linked to another DNA sequence
      which influences the trait. Association studies compare the value of a
      quantitative trait between different marker genotype classes in a population,
      without regard to family structure. Linkage studies compare the value of a
      quantitative trait between marker genotype classes within families or within a
      population (usually derived from a cross between inbred lines) which is
      segregating for both marker and quantitative trait loci. The most commonly used
      analytical methods for determining the significance of association or linkage
      between marker and quantitative trait loci, and for estimating parameters such as
      recombination rate and quantitative gene action, are least-squares and maximum
      likelihood. Both methods may be used to test either single markers or the
      interval between flanking markers, and both suffer from the need to minimize type
      I and type II error rates with multiple tests.

PMID- 9198600
TI  - Beta-tubulin gene polymorphism and benzimidazole resistance in trichostrongylus
      colubriformis.
AB  - The complement of beta-tubulin alleles in Trichostrongylus colubriformis
      populations was examined and found to undergo changes similar to those previously
      reported for Haemonchus contortus following selection for benzimidazole (BZ)
      resistance. Genomic DNA from BZ-resistant and -susceptible strains was probed
      with a series of overlapping fragments derived from a T. colubriformis beta
      tubulin gene. A susceptible population showed a high level of polymorphism
      (detected as RFLPs with several enzymes and directly by sequence analysis) at a
      locus, tcb-1, which appears to be the homologue of the gru-1 locus in H.
      contortus. This polymorphism disappeared following selection for BZ resistance,
      leaving a single tcb-1 allele in the resistant population. The same single allele
      was present in 2 additional, unrelated resistant populations. These data support
      the hypotheses that tcb-1 and gru-1 are major determinants of BZ susceptibility
      and hence a major target of BZ-resistance selection.

PMID- 9198601
TI  - Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis
      and other cestodes in a rural dog population in Uruguay.
AB  - A survey was undertaken to determine both the prevalence of, and reinfection
      rates with Echinococcus granulosus and other cestodes in the Department of
      Florida, Uruguay. Baseline prevalence was determined in 303 rural dogs which
      then, in 4 groups, were re-examined 2, 4, 8 or 12 months later. Baseline
      prevalences for E. granulosus, Taenia hydatigena, Taenia ovis and Dipylidium
      caninum were 13.2, 13.9, 2.3 and 13.2%, respectively. The frequency distribution
      of E. granulosus was over-dispersed. Dogs in the population became infected with
      E. granulosus between 2 and 4 months after treatment (prevalences at 2, 4, 8 and
      12 months were 0, 6.8, 18.6 and 27.9%, respectively). There was no indication
      that there was a predisposition of dogs to infection with the Odds Ratio being
      1.0. Dogs were infected with T. hydatigena and D. caninum within 2 months and
      with T. ovis between 2 and 4 months after treatment. The implications of these
      different rates of reinfection in the dog population on anthelmintic control
      strategies against cystic echinococcosis are discussed.

PMID- 9198602
TI  - Effect of Freund's adjuvants on guinea pigs infected with, or vaccinated against,
      Trichostrongylus colubriformis.
AB  - Soluble antigens that protected guinea pigs against experimental challenge with
      Trichostrongylus colubriformis were found to be less effective if injected as
      emulsions in Freund's adjuvants. This occurred despite the production of higher
      antibody titres in guinea pigs given emulsified antigen. Investigations of this
      phenomenon showed that an intraperitoneal injection of Freund's complete adjuvant
      (FCA) delayed rejection of primary infections and partially abrogated resistance
      to challenge infection. Administration of FCA/antigen emulsion to infected guinea
      pigs resulted in a prolonged blood eosinophilia which paralleled the increased
      longevity of the parasitosis. These findings suggest the need for caution in the
      selection of adjuvants for vaccination against gastrointestinal nematodes.

PMID- 9198603
TI  - Serum mast cell proteinase responses of sheep to challenge with Trichostrongylus
      colubriformis and the effect of dexamethasone treatment.
AB  - Eight-month-old random bred Romney wethered lambs were reared nematode-free in
      pens and assigned to 4 groups of 5 lambs. Lambs in 2 groups were dosed orally,
      twice a week, with 5000 Trichostrongylus colubriformis infective larvae (L3) for
      the duration of the experiment. These 2 groups were treated weekly with
      dexamethasone (0.5 mg kg(-1) body-weight), one between days -7 and 70, the other
      between days 77 and 147. A third group was dosed with L3 until anthelmintic
      treatment on day 133. A fourth group remained uninfected throughout and served as
      a control group. Nematode eggs in sheep faeces (FEC) were monitored at weekly
      intervals. Serum samples were taken twice a week and assayed for sheep mast cell
      proteinase (SMCP). Serum levels of SMCP in uninfected control sheep were 459 +/-
      190 pg ml(-1). Twenty-eight days after nematode dosing commenced, SMCP levels
      were significantly above control sheep levels and after 49 days reached a plateau
      level of 1154 +/- 364 pg ml(-1). The SMCP response persisted even after cessation
      of dosing, and SMCP levels remained significantly above control levels to the end
      of the experiment (day 213). Dexamethasone treatment prevented elevation of SMCP
      and resulted in a rapid reduction of extent SMCP levels in resistant sheep.
      Overall, serum levels of SMCP were significantly correlated (P<0.001) with
      specific anti-T. colubriformis L3 antibody in serum (r = 0.601, d.f. = 78), blood
      eosinophils (r = 0.609, d.f. = 78) and log(FEC+15) (r = -0.521, d.f. = 78). These
      results show that serum levels of SMCP correlate with other indicators of
      parasitism and may have potential use as a non-invasive indicator of
      gastrointestinal mast cell responses to nematode infection.

PMID- 9198605
TI  - The 10th NIMH International Conference on Mental Health Problems in the General
      Health Care Sector. Bethesda, Maryland, July 15-16, 1996. Abstracts.

PMID- 9198604
TI  - Drug-abbreviated infections and development of immunity against Trichostrongylus
      colubriformis in sheep.
AB  - A protective immune response without liveweight loss can be induced in sheep
      against T. colubriformis but results depend on the anthelmintic used and duration
      of immunizing infections. More than 90% protection was achieved in sheep
      immunized by three 15- or 7-day oxfendazole abbreviated infections or three 21
      day nonabbreviated infections. Only 41% protection was induced by 3-day
      oxfendazole abbreviated infections. Significantly higher worm burden and faecal
      egg counts were present after challenge in sheep immunized by 7-day levamizole
      abbreviated infections compared to 7-day oxfendazole abbreviated infection.
      Liveweight gains of sheep immunized by 15- and 7-day abbreviated infections were
      not significantly different than non infected controls. Liveweight loss seemed to
      be associated with high activity of mucus peroxidase and high numbers of
      eosinophils in the intestinal lumen. High parasite numbers seemed to be
      associated with low activity of alkaline phosphatase in mucus. Mucus peroxidase,
      arylsulphatase, larval migration inhibition of mucus, mucus or serum antibody
      against L3 excretory/secretory antigen or somatic L3, L4 and adult antigen were
      not associated with protection.

PMID- 9198606
TI  - Nomenclature for factors of the HLA system, update November/December 1996. WHO
      NOmenclature Committee for Factors of the HLA System.

PMID- 9198608
TI  - Science and sinuses.

PMID- 9198607
TI  - Electronic publishing--the next steps.

PMID- 9198609
TI  - Patient rights, provider rights: balancing the conflict.
AB  - A federal appeals court decision in an HIV discrimination case raises tough
      questions about the rights of providers vs. the rights of patients.

PMID- 9198610
TI  - [Diagnosis and disease types of diabetes mellitus].

PMID- 9198611
TI  - [Intensified treatment of diabetes mellitus and prevention of the development or
      progression of complications].

PMID- 9198612
TI  - [Abnormalities of vascular wall metabolism and arteriosclerosis].

PMID- 9198613
TI  - [Visceral fat syndrome and arteriosclerosis].

PMID- 9198614
TI  - [Abnormalities in nucleic acid metabolism and gout].

PMID- 9198615
TI  - [Calcium metabolism and osteoporosis].

PMID- 9198616
TI  - [Molecular biological analysis of hypothalamic-hypophyseal hormones].

PMID- 9198617
TI  - [Thyroid dysfunctions as autoimmune diseases].

PMID- 9198618
TI  - [Factors regulating circulation and hypertension--a molecular biological
      approach].

PMID- 9198619
TI  - [Early discovery of hepatocellular carcinoma].

PMID- 9198620
TI  - [Diagnosis and treatment of chronic pancreatitis].

PMID- 9198621
TI  - [Physiopathology, diagnosis, and treatment of inflammatory bowel diseases].

PMID- 9198622
TI  - [Physiopathology and treatment of multiple sclerosis].

PMID- 9198623
TI  - [Current status of diagnosis and treatment of senile dementia].

PMID- 9198624
TI  - [Parkinson disease--diagnosis and treatment].

PMID- 9198625
TI  - [Etiology and treatment of adrenal diseases of the current interest].

PMID- 9198627
TI  - [Etiology and treatment of hyperlipemia].

PMID- 9198626
TI  - [Diabetes mellitus and insulin resistance].

PMID- 9198629
TI  - [Drug-allergy].

PMID- 9198628
TI  - [Differential diagnosis and treatment of chronic rheumatoid arthritis].

PMID- 9198630
TI  - [Pneumonia of the aged].

PMID- 9198631
TI  - [Drug-induced pneumonitis and related diseases].

PMID- 9198632
TI  - [Treatment of hypertension with organ dysfunctions--the current trend].

PMID- 9198633
TI  - [Physiopathology and treatment of angina pectoris].

PMID- 9198634
TI  - [Cardiomyopathy and enlarged hearts of athletes].

PMID- 9198635
TI  - [Chemotherapy of leukemia].

PMID- 9198636
TI  - [Hemolytic anemia--recent findings--with special reference to erythrocyte
      membrane abnormalities].

PMID- 9198637
TI  - [Relationship between virus and bacterial infections--with special reference to
      respiratory tract infections].

PMID- 9198638
TI  - [Diagnosis and treatment of deep-seated mycosis].

PMID- 9198639
TI  - [Rapidly progressive glomerulonephritis and ANCA--anti-GBM antibody].

PMID- 9198641
TI  - [Clinical characteristics of jaundice].

PMID- 9198640
TI  - [Hemodialysis].

PMID- 9198642
TI  - [Jaundice: differential diagnosis].

PMID- 9198643
TI  - [Acute hepatitis, fulminant hepatitis, and jaundice].

PMID- 9198644
TI  - [Liver cirrhosis and jaundice].

PMID- 9198645
TI  - [Drug-induced hepatic dysfunction and jaundice].

PMID- 9198646
TI  - [Idiopathic biliary liver cirrhosis, primary sclerosing cholangitis, and
      jaundice].

PMID- 9198647
TI  - [Constitutional jaundice].

PMID- 9198648
TI  - [Progress in the instrument used for diagnosis of obstructive jaundice. 1)
      Ultrasonic endoscope].

PMID- 9198649
TI  - [Progress in instrument used for diagnosis of obstructive jaundice. 2)
      Intraductal ultrasonography].

PMID- 9198650
TI  - [Progress in instrument for diagnosis of obstructive jaundice. 3) Cholangioscopy-
      with special reference to diagnosis by an oral or percutaneous transhepatic
      cholangioscope].

PMID- 9198651
TI  - [Progress in instrument used for diagnosis of obstructive jaundice. 4. MRCP].

PMID- 9198652
TI  - [Obstructive jaundice: progress in instrument used for diagnosis. 5) CT and MRI].

PMID- 9198653
TI  - [Cholelithiasis and jaundice].

PMID- 9198654
TI  - [Malignant bile duct diseases and jaundice].

PMID- 9198656
TI  - [Medical treatment of obstructive jaundice].

PMID- 9198655
TI  - [Pancreatic diseases and jaundice].

PMID- 9198657
TI  - [Surgical treatment of obstructive jaundice].

PMID- 9198658
TI  - [Multidisciplinary treatment of obstructive jaundice in malignant diseases].

PMID- 9198659
TI  - [Obstructive jaundice: new development in the medical approach to the bile duct
      and pancreas. Discussion].

PMID- 9198660
TI  - [Case of p-ANCA-positive rapidly progressing glomerulonephritis requiring
      hemodialysis: effectiveness of anti-MPO antibody determiantion in predicting
      pulmonary hemorrhage].

PMID- 9198662
TI  - [Case of a new type of Tsutsugamushi disease associated with
      meningoencephalitis].

PMID- 9198661
TI  - [Case of diabetic nephropathy with improvement in marked systemic edema following
      continuous subcutaneous infusion of heparin].

PMID- 9198663
TI  - [Case of ectopic ACTH-producing small cell carcinoma of the lung: a reduction in
      tumor size after chemotherapy in spite of a marked rise in the plasma ACTH
      level].

PMID- 9198664
TI  - [Case of acute immune hemolytic anemia developing during fluorouracil
      administration following surgery of colonic cancer].

PMID- 9198665
TI  - [Chemokines and anti-chemokine therapy in kidney diseases].

PMID- 9198666
TI  - [Superantigens and glomerulonephritis].

PMID- 9198667
TI  - Understanding the mechanisms of sustained signaling and T cell activation.

PMID- 9198668
TI  - When do microbes stimulate rheumatoid factor?

PMID- 9198670
TI  - Contempo 1997.

PMID- 9198669
TI  - Characterization of phosphofructokinase II and regulation of fructose 2,6
      bisphosphate levels in Trichoderma reesei.
AB  - Phosphofructokinase II (PEK II) from Trichoderma reesei was partially purified
      (247-fold). The calculated Km values for fructose 6-phosphate and ATP were 0.7 mM
      and 40 microM, respectively. Upon incubation in the presence of [gamma-32P]ATP,
      the enzyme formed a radioactive phosphoprotein with molecular mass of 67 kDa in
      autoradiography analysis after SDS-PAGE. Upon incubation in the presence of ATP
      Mg and the catalytic subunit of cAMP-dependent protein kinase, its activity was
      not modified. The same result was obtained when a cell-free extract of T. reesei
      was incubated with ATP-Mg and cAMP. 2,4-Dinitrophenol caused a transient rise in
      cAMP levels in the fungal cell. The results provide evidence that the fructose
      2,6-bisphosphate level in T. reesei is independent of cAMP concentrations and not
      related to a cAMP-dependent mechanism, but to the availability of substrate
      fructose 6-phosphate.

PMID- 9198672
TI  - [Neurovegetative symptoms in infants with sleep-related respiratory disorders].
AB  - A relationship between neurovegetative symptoms and an increased risk of sudden
      infant death (SID) has been frequently described. Such symptoms are vomiting
      because of gastroesophageal reflux, breathing disorders while nutritive sucking,
      excessive sweating during sleep, prolonged apneas and apneas with associated
      symptoms, further unexplained episodes of cyanosis, pallor and loss of muscle
      tone. An acute decompensation of the cardiorespiratory autonomic system during
      sleep is currently discussed to be one of the causes of SID. Polysomnographic
      investigations are used to diagnose sleep related cardiorespiratory autonomic
      dysfunction. In this study, infants up to the age of 5 months were examined using
      polysomnography throughout their entire nocturnal sleep. The findings from 79
      infants with neurovegetative symptoms were compared with the results from 163
      healthy control children. Indications of an impaired respiratory regulation
      during sleep were shown to be significantly more frequent in infants with
      neurovegetative symptoms. In particular the occurrence of periodic breathing with
      a high frequency of periodic apnea plus a large number of acute decreases in
      oxygen saturation could be shown in infants with neurovegetative symptoms. The
      findings were most pronounced during the first 1.5 months after birth. The
      results of this investigations lead to the conclusion that, in the case of young
      infants with breathing abnormalities, neurovegetative symptoms can frequently be
      observed. The occurrence of such symptoms should therefore be a reason for a
      polysomnographic examination.

PMID- 9198671
TI  - [Simultaneous measurements of end-expiratory and transcutaneous carbon dioxide
      partial pressure in ventilated premature and newborn infants].
AB  - BACKGROUND: The aim of the present trial was to study the relationship between
      end-tidal pCO2 (p(et)CO2) and transcutaneous pCO2 (ptcCO2) after in-vivo
      calibration in ventilated newborns. PATIENTS: 61 end-tidal and transcutaneous
      pCO2 measurements were simultaneously performed in 30 ventilated preterm and term
      newborn infants (weight at birth 1862.6 +/- 981.9 g). METHOD: End-tidal pCO2 was
      measured in mainstream mode at the end of the endotracheal tubus (Novametrix 7000
      Medical Systems Inc., USA, dead volume of the chamber 0.6 ml). Transcutaneous
      pCO2 was measured by means of a Servomed (SMK 365 Hellige, FRG) analyser.
      RESULTS: The statistical analysis demonstrated a good correlation (r = 0.72, p <
      0.001) between ptcCO2 (mean +/- SD, 44.3 +/- 11.2 mmHg) and p(et)CO2 (32.4 +/-
      10.4 mmHg). A considerable difference between transcutaneous and end-tidal pCO2
      values was observed (p(tc-et)CO2 = +11.9 +/- 8.7 mmHg). This phenomenon was
      probably caused by ventilation-perfusion disturbances in the studied critically
      ill neonates. The statistical analysis revealed that the absolute magnitude of
      the P(tc-et)CO2 difference was independent from disease, episodes of spontaneous
      respiration or of respiratory frequency. CONCLUSIONS: Capnographic determination
      of P(et)CO2 provides informations about alveolar ventilation-perfusion
      disturbances. Capnography enables the on-line control of end-tidal pCO2 in
      neonates with respiratory failure. It cannot replace transcutaneous pCO2
      measurements or blood gas analysis but it can reduce its frequency in clinically
      stable patients. The analysis of the capnogram can be used to optimise artificial
      ventilation. A quantitative evaluation of the capnogram by calculation of
      Muranyi's-CO2-Index was possible only in 28% of the ventilated newborns which
      limits its value in such patients.

PMID- 9198673
TI  - [Chronic interstitial lung diseases in childhood--an overview].
AB  - The spectrum of chronic interstitial lung disease in children includes a large
      and heterogeneous group of rare disorders. This paper reviews these disorders by
      focussing on basic pathophysiological mechanisms, and by discussing the
      difficulties in the classification of these diseases. Diagnostic and therapeutic
      approaches are also listed. The overall prognosis is dubious and mortality
      remains high.

PMID- 9198674
TI  - [Arteriovenous malformations of the cervical spinal cord].
AB  - Arterio-venous malformations (AVM) of the CNS are considered uncommon lesions in
      childhood, but is a main cause for subarachnoid haemorrhage (SAH) of children. We
      report a case of a 14-year-old girl with an AVM localized in the cervical spine:
      after an acute event with SAH she shows the clinical features of a cervical
      myelopathy-syndrome. MRI and selective angiography show an AVM, originating from
      the right vertebral artery. Patients with AVM have a higher incidence of
      recurrent bleeding with SAH, hematomyelia or infarction and even cord
      compression. This grave sequel makes it necessary to treat AVM e.g. with
      embolization.

PMID- 9198675
TI  - [Cataplexy in type C Niemann-Pick disease].
AB  - Cataplexy usually occurs as a part of the tetrad of clinical phenomena of
      idiopathic narcolepsy. Symptomatic cases are rare. A 4 years old girl from
      consangineous parents had recurrent loss of muscle tone and fell to the ground,
      when she laughed. The EEG was normal. Prolonged neonatal jaundice with
      cholestasis, hepatosplenomegaly, mental regression, supranuclear ophthalmoplegia,
      and foam cells led to the diagnosis of Niemann-Pick disease type C with
      symptomatic cataplexy. Symptomatic forms of the narcolepsy-cataplexy complex
      should be considered, when there is an early onset before puberty, cataplectic
      attacks predominate the narcoleptic attacks, and when additional neurological
      symptoms occur. Symptomatic cataplexy occurs in Niemann-Pick disease type C. It
      is considered to be the result of lesions of the pontine reticular formation.

PMID- 9198676
TI  - [Diagnosis and antimicrobial therapy of bacterial meningitis. Recommendations of
      the "CNS Diseases" Study Group of the Paul Ehrlich Society of Chemotherapy e.V.
      and the German Society of Pediatric Infectiology].

PMID- 9198677
TI  - [Professor Sten Ronnberg: the extent of gambling in Sweden is surveyed in a
      research project covering several years].

PMID- 9198678
TI  - [USA: prosecutors investigate the biggest hospital corporation].

PMID- 9198679
TI  - [Misunderstanding about the role of physicians employed by the insurance
      authorities. Documentation for increased security].

PMID- 9198680
TI  - [The phenomenon "visual stress" visualized].

PMID- 9198681
TI  - [The question on euthanasia should be postponed].

PMID- 9198682
TI  - [The megaphone of power?].

PMID- 9198683
TI  - [Early discharge--a positive and safe type of care].

PMID- 9198684
TI  - [Euthanasia or long-term anesthesia?].

PMID- 9198685
TI  - [Malignant hyperthermia--genetic diagnosis is not yet possible].

PMID- 9198686
TI  - [Developmental possibilities in neurosurgery].

PMID- 9198687
TI  - [Pancreatic cancer, difficult to diagnose. Few early symptoms, often normal
      laboratory values].

PMID- 9198688
TI  - [Pain relief. A new medical specialty focused on prolonged pain].

PMID- 9198689
TI  - [Differential diagnosis in epilepsy. Anamnesis is still the most important
      guide].
AB  - Epilepsy is defined by the WHO as "a chronic brain disorder of various
      aetiologies characterised by recurrent seizures due to excessive discharge of
      cerebral neurones." There are many other episodic conditions including systemic,
      neurological and psychiatric disorders, which may be confused with epileptic
      seizures but are not the result of epileptic neuronal discharge. The principal
      differential diagnoses in cases of episodic seizures in adults and children are
      outlined in this review, and the importance of adequate history taking is
      stressed. Correct interpretation of the history is dependent upon the physician's
      recognition of the clinical features typical of epileptic seizures. Both the
      importance and the limitations of electroencephalography (EEG) are discussed. The
      contribution of EEG in cases where a diagnosis of therapy-resistant epilepsy has
      been questioned is exemplified in case studies of 42 patients, of whom 43 per
      cent were found to have psychiatric disease only, 26 per cent to have epilepsy
      only, 12 per cent to have both epileptic seizures and episodic symptoms of
      psychiatric origin, and the remaining 19 per cent to have episodic disorders of
      non-epileptic and non-psychiatric origin. The importance of adequate history
      taking before making a diagnosis of epilepsy is emphasised, as is the conclusion
      that an incorrect diagnosis of epilepsy often causes more harm than postponing
      the diagnosis until it becomes more clear.

PMID- 9198690
TI  - [Calcium and folic acid are delicate knotty questions].

PMID- 9198691
TI  - [More flexible reposition with local analgesia. Intra-articular analgesia tested
      in shoulder dislocation].

PMID- 9198692
TI  - [Nuclear medicine. Now a specialty in itself].

PMID- 9198693
TI  - "The doctor is coming--on disease, medicine and cure in art." On cure and
      doctors' failure to cure.

PMID- 9198694
TI  - [The physician is ecologic responsibility].

PMID- 9198695
TI  - [Unnecessary follow up of myoma. Bleeding disorders are specific symptoms for
      sarcoma].

PMID- 9198696
TI  - [Ramadan. A month of fasting with risk for both nocturnal overeating, dehydration
      and starving].

PMID- 9198697
TI  - ["Unknown structure" probably already described].

PMID- 9198698
TI  - [Education by medical ethics. Should be included close to the clinical reality].

PMID- 9198699
TI  - Microbial genome sequencing opens door to new world.

PMID- 9198700
TI  - Notice of duplicate publication.

PMID- 9198701
TI  - Out with the jab, in with the painless pills.

PMID- 9198702
TI  - [Comparative stability evaluation of dynamic hip screw and gamma-nail
      osteosyntheses in unstable pertrochanteric femoral osteotomies].
AB  - In 24 human cadaver femora standardized instable pertrochanteric osteotomies were
      created. The right and left femur of each pair were alternately selected for
      osteosyntheses with the gamma nail and the dynamic hip screw. Afterwards an
      examination of stability was performed. Cyclical loads were increased in 500 N
      increments to the maximum loading capacity, while the deformation rate was
      continuously measured. Radiographs were taken to prove the results of loading.
      The mean deformation was much greater in the DHS group than for the gamma nail,
      the maximum load to failure was significantly lower. Femoral shaft fractures
      caused by the loading occurred five times as often in the gamma nail
      osteosyntheses than in the DHS.

PMID- 9198703
TI  - [Does heparin modify the course of chronic abscess-forming peritonitis in the
      animal model?].
AB  - After laparotomy and inoculation of a Bacteroides fragilis suspension (2 ml with
      10(8) CFU/ml), we induced chronic abscess-forming peritonitis in rats (n = 19,
      untreated). Fifteen animals were treated with heparin 30 IU, administered s.c.
      from day 1 after inoculation of the bacteria onwards. The main groups were
      divided into three subgroups (n = 8/5/6 and n = 5/5/5), which were observed for
      3/7/14 days, respectively. On days 3 and 7, abdominal swabs were not only B.
      fragilis positive, but also showed severe polyvalent mixed infection after
      translocation of intestinal bacteria into the abdominal cavity. In the heparin
      group, B. fragilis positive swabs were reduced and translocation was inhibited (P
      < 0.05 for days 3 and 7). In the untreated group, blood cultures were B. fragilis
      positive on days 3/7/14 in 3/2/1 animals versus 0/1/1 in the heparin group.
      Adhesions were found in the untreated group in 1/4/5 animals, whereas in the
      heparin group there were no adhesions (P < 0.05 for days 7 and 14). However,
      intra-abdominal abscesses were also diminished in the heparin group (0/2/1)
      compared with the untreated animals (2/4/6, P < 0.05 for day 14). Therefore,
      heparin was shown to have a favourable influence on chronic abscess-forming
      peritonitis in an animal model.

PMID- 9198704
TI  - [Violation of patient education responsibility. Implications and outlook].
AB  - In both jurisdiction and medical science, given conditions require appropriate
      intervention, which may in turn result in norms being created. Norms, however,
      counteract individuality. An essential prerequisite for free decision--making is
      an absolute awareness of all possibilities available. Therefore the
      physician/surgeon too, is obliged to impart all relevant information to the
      patient prior to an operation to enable the patient to reach a decision, either
      to agree to or refuse the operation. This process of information transfer may
      sometimes fail on one or both sides. Treatment errors are usually classified
      according to scientific medical practice. In the case of "breach to duty in
      information patient" the final decision is the judges. As judicial decisions are
      not foreseeable, the communication between patient and surgeon thus becomes
      standardized and doctors tend to become defensive, resulting in the information
      becoming even more extensive covering all possible situations. There is no
      guarantee of success in surgery. Selective perception on the part of the patient
      is unavoidable and confidence in the relationship between patient and surgeon is
      beneficial to the patient's rehabilitation. Therefore, we should strive to
      decriminalize the preoperative talk held between surgeon and patient.

PMID- 9198705
TI  - [Gardner syndrome and thyroid gland carcinoma].

PMID- 9198706
TI  - [Gardner syndrome and thyroid gland carcinoma].
AB  - We report on the case of a 23-year-old female with a 5-year history of Gardner's
      syndrome, who developed a bifocal, papillary carcinoma of the thyroid. The
      combination of familial adenomatous polyposis with a thyroid cancer is a rare but
      well-documented association. Typically, histology reveals a multifocal, papillary
      tumour with a predominantly good prognosis. This type of carcinoma is almost
      exclusively confined to females in their second decade of life, and it may, in
      fact, precede the onset of the polyposis manifestation. Patients suffering from
      familial adenomatous polyposis should therefore undergo regular clinical
      examination of the thyroid gland. If a neoplastic lesion is suspected, immediate
      scintigraphic evaluation should be carried out, with fine-needle aspiration of
      equivocal foci if necessary, and/or intraoperative frozen section. When a
      carcinoma is found, total thyroidectomy with dissection of the central lymph
      compartments should be considered the treatment of choice because of the high
      likelihood of the tumour being multicentric.

PMID- 9198707
TI  - [Rare differential diagnosis of breast tumor. Giant cell tumor of the ribs].
AB  - We report a case of a breast tumor. As carcinoma of the breast was suspected, a
      biopsy was taken and a very rare osteoclastoma originating in the rib was
      identified. Semimalignant bone tumors tend to recur locally. The symptoms are
      nonspecific; the initial diagnosis is often made late. To differentiate the
      diagnosis, one should think about primary and secondary bone diseases and tumors
      of the organs of the thorax. In our case, the tumor was completely resected,
      including the ribs, and the defect was covered with a corium plasty. In this way,
      we are able to save the breast. We discuss different methods for covering chest
      wall defects.

PMID- 9198708
TI  - [ICPM-independent documentation of new reimbursement forms--method and 1995
      results].
AB  - The structural health care law (known as the Gesundheitsstrukturgesetz or GSG) of
      the Federal Republic of Germany has been enacted to replace the covering cost
      prices by various forms of payment. On the basis of the Godesberg Diagnosis and
      Therapy Catalogue, a new system has been developed that assesses all new
      implications of the care benefit law. With the help of intelligent plausibility
      tests, a particular case (PC) or a special rate (SR) is suggested. The
      documentation system works without ICPM numbers. The conversion of diagnosis and
      therapies to ICD-10/ICPM numbers is possible. The results of the first half of
      1995 and the second half of 1995 show that only two-fifths of operations can be
      assessed with PC or SR. Neither emphasis on certain operations nor the more
      differentiated illnesses are recognised as extra costs by the GSG regulations.
      Complete and correct documentation is achieved by a strict and stratified control
      system.

PMID- 9198709
TI  - [Diaphragm replacement. An animal experiment study].
AB  - BACKGROUND: Only a few indications exist for diaphragm replacement: aplasias,
      tumours and accidents. The defect may be so extensive that it is impossible to
      close the gap. Allogenic and autologous materials are proposed for replacement of
      the diaphragm. The disadvantages of allogenic materials are recurrence rates of
      up to 20% and a high rate of malalignment of thoracic muscles and bones; the
      implication of autologous materials requires a longer operation time and no long
      term results exist. To avoid these disadvantages, we have tested a material from
      bovine serosa, which is absorbable for a short time, for diaphragm replacement.
      METHODS: The merits of four methods of diaphragmatic hernia repair were evaluated
      in animals. One hundred Sprague-Dawley rats underwent laparotomy. The control
      group had an incision in the diaphragm with primary repair. The other four groups
      underwent partial resection of the left hemidiaphragm. The defects were repaired
      in 20 rats with lyophilized dura, in 20 with polytetrafluoroethylene (PTFE), in
      20 with autologous transversus muscle and in another 20 with absorbable serosa
      from a cow. The animals were followed up by electromyography (EMG) and post
      mortem physical and histological examinations after 3 and 6 months. RESULTS:
      Eighty-nine animals survived the operations. The EMG showed normal function for
      the absorbable material and the transversus muscle. Only scanty physiological
      waves were recorded in the PTFE group. The examination for stretching and stress
      showed good results for all materials tested. The histological examinations
      showed strong foreign body reactions in the dura and PTFE groups. The absorbable
      bovine serosa had vanished after 3 months postoperatively. CONCLUSION: We
      conclude that bovine serosa can be recommended for the treatment of diaphragmatic
      defects.

PMID- 9198710
TI  - [Morphologic correlation of functional abdominal wall mechanics after mesh
      implantation].
AB  - Modern surgical hernia repair depends increasingly on synthetic meshes for
      reconstruction of the abdominal wall. Despite the undisputed advantages of the
      synthetic meshes currently available, reports of late complications after
      implantation are accumulating. It is essential that the synthetic meshes be
      improved, but this makes a standardized animal model necessary for evaluation of
      their biocompatibility on both functional and morphological levels. In the
      present study, commercially available polypropylene and polyester meshes were
      implanted in a rat model, and detailed morphological and morphometric analysis
      were carried out. Correlations between the morphological and morphometric data
      and the function of the artificial abdominal wall were then sought. In summary,
      the data show that the mesh construction currently available are oversized and
      definitely restrict the function of the artificial abdominal wall. The degree of
      inflammation and fibrosis, the pattern of fibrosis, and the composition of the
      extracellular matrix exert decisive influences on the function. Fibrosis and
      inflammation are caused less by the material itself, however, than by its
      density, the way it is processed, and its surface. Future, that is to say second
      generated, mesh constructions should be designed with the aims of reducing the
      amount of material used and finding material-specific processing methods in mind,
      to improve the functionally and morphologically defined biocompatibility.

PMID- 9198711
TI  - [Occupational neoplasms in Poland in the years 1971-1994].
AB  - The analysis of the incidence of malignant neoplasms, recognised as occupational
      disease, in Poland during the years 1971-94 was based on occupational disease
      certificates sent obligatory to the Nofer institute of Occupational Medicine
      (Lodz) by all sanitary and epidemiological stations under the Ministry of Health
      and Social Welfare and the Polish State Railways. During the period study 1118
      occupational neoplasms were diagnosed, including 1042 cases (93.2%) of neoplasms
      in males. Among males malignant Ineoplasms of lung (36.1%), larynx (25.5%),
      bladder (14.7), skin (6%), lymphatic and haematopoietic tissue (3.4%) and pleura
      (2.9%) were most common. The rate occupational neoplasms in the total number of
      neoplasms registered accounted for 0.11% in males and 0.01% in females. PAH
      (29.1%), asbestos dust (18.8%), ionizing radiation (13.8%), chromium and its
      compounds (13.5%) and benzidine (9.8%) belong to the most frequent causes of
      malignant neoplasms in males, and ionizing radiation (31.5%) and asbestos dust
      (30.3%) in females. The number of neoplasms recognised as occupational disease is
      very low. Underestimation of occupational neoplasms is very common throughout the
      world, but it is particularly high in Poland if we take the incidence of pleura
      mesothelioma as an example. This is mainly due to: (1) the lack of clinical and
      morphological specificity of occupationally induced neoplasms; (2) a long
      latency; (3) the influence of other factors confounding the effect of
      occupational exposure; (4) a relatively small number of occupational carcinogens
      identified thus far; (5) limited knowledge of occupational carcinogens and
      criteria for occupational disease certification, and unsatisfactory interviewing
      skills among doctors who diagnose cancer disease. The identification of a harmful
      factor and the size of exposure to it, belongs to the weakest point in certifying
      the occupational background of the disease. The essential conclusions presented
      stress the urgent need for establishing the system facilitating the diagnosis and
      certification of occupational neoplasms.

PMID- 9198712
TI  - [Identification of working conditions in small enterprises. A project for
      drafting hygienic recommendations for employers--concepts for monitoring].
AB  - One of the outcomes of the transformation process which has been lasting already
      for few years is a dynamic development of so called small business. The level of
      knowledge of work hygienic and sanitary conditions in very limited in this group
      of enterprises. The research project which is being now implemented attempt a
      comprehensive identification and then evaluation of working conditions in small
      enterprises as well as the disclosure of essential failures and their sources.
      The results obtained will be used as a basis for developing hygienic
      recommendations and guidelines for employers how to improve health and hygienic
      conditions. The first step in the project implementation was to select provinces
      (voivodships) and enterprises operating there, in which the research is going to
      be carried out and to develop a research instrument in the from of a
      questionnaire which will be used to collect information on working conditions in
      enterprises selected. The questionnaire is composed of two sections: (1) an
      essential one dealing with hygienic and sanitary aspects of the work environment
      and conditions understood in their broadest sense, and (2) a supplementary one
      addressed entirely to employers and raising the question of their awareness as to
      the hazards related to the work environment.

PMID- 9198713
TI  - [Evaluation of selected functional circulation parameters of workers from various
      occupational groups exposed to electromagnetic fields of high frequency. III. 24
      h monitoring of arterial blood pressure (ABP)].
AB  - The problem of blood pressure regulation in persons occupationally exposed to
      electromagnetic fields (EMF) has not as yet been elucidated, and most data come
      from studies carried out long time ago (1960-70) in the former Soviet Union. Our
      study was aimed at verifying the Soviet data by means of modern methods. Together
      with traditional methods, a 24-h monitoring of arterial blood pressure (ABP)
      using a Medilog ABP kit (Oxford) were employed. Measurements were taken
      automatically every 0.5 h during daily activities and every 1 h during the night
      rest (about 41 measurements/day). The mean systolic and diastolic blood pressure
      and heart rate were calculated over day (BPSDOver, BPDOver, HROver), during daily
      activities (HPDD, BPSD, HRD) and during the night rest (BPSN, BPDN, HRN). The
      subjective and objective examinations were carried out as well as resting ECG and
      a 24-h Holter were performed (the results have been published earlier). The study
      covered male workers of middlewave broadcast stations (71), radioservice (40) and
      radio line stations (42). The subjects were aged 21-60 years and the duration of
      their work with devices generating high frequency EMF ranged between 1 and 42
      years. The first group of workers was exposed to EFM at the frequency of 1 Mhz,
      the second at about 150 Mhz and the third group, not exposed, served as the
      control group. The study revealed that the mean arterial blood pressure and the
      day/night blood pressure variability indicator showed no significant differences
      between the groups, whereas the daily heart rate was significantly lower in the
      workers of middlewave broadcast stations in comparison with the controls despite
      similar type of work as far as physical effort and psychic burden are concerned,
      and similar non-occupational activities. The day/night heart rate variability
      indicator was significantly lower in the groups exposed. The decreased value of
      this indicator may suggest the occurrence of disorders in the neurovegetative
      regulation. In persons employed at radioservice stations a higher incidence of
      the increased arterial blood pressure, in comparison with the control group, was
      observed.

PMID- 9198714
TI  - [Frequency of birth defects in newborns in four regions of Poland].
AB  - Records of births from registry offices in seven provinces (Walbrzych, Piotrkow
      Trybunalski, Suwalki, Krosno, Rzeszow, Przemysl, Tarnobrzeg) making four regions
      (south-western, central, north-eastern and south-eastern) were used for the
      analysis of the geographical distribution of congenital malformations. This area
      is inhabited by approximately 10% of the whole population with annual number of
      briths equal to 9% of the total number in Poland. The incidence of congenital
      malformations was analysed in 21.167 newborns taking into consideration such
      variables as smoking and other habits and occupational of parents, maternal age,
      and environmental pollution. In the cohort under study the incidence of
      malformations was different and it was as follows: Walbrzych-1.92%, Rzeszow
      1.42%, Tarnobrzeg-1.37%, Suwalki-1.23%, Krosno-1.16%, Piotrkow Trybunalski-1.12%
      and Przemysl-0.7%. The incidence of birth defects in infants born to young
      mothers (< 20 years) was 1.8% and to older ones (> 35) 1.9%. A comprehensive
      analysis of the environmental pollution revealed its highest level in the south
      western region (the Walbrzych province) in comparison with other study areas.

PMID- 9198715
TI  - [A qualitative evaluation of health risk associated with occupational inhalation
      exposure to cadmium in production plants in Poland].
AB  - In Poland several thousand people work under exposure to cadmium with different
      concentrations. The concentrations observed range between the level which is not
      determinable and the level above 0.3 mg/m3, at the MAC value equal to 0.04 mg/m3.
      In 1993 the cadmium classification was modified by the International Agency for
      Research on Cancer (IARC). Previously cadmium had been proved to be carcinogenic
      to animals (group 2B). At present it is classified in group 1, namely in the
      group of substances proved to be carcinogenic to humans. The cadmium MAC value,
      mandatory in Poland, has been set on the basis of the data on its chronic, toxic
      renal effects, but its critical effect in the form of cancer has not been taken
      into consideration. The author, using the results of epidemiological studies
      carried out by Thun et al., presented three dose-response functions which
      describe the relationship between the size of exposure and the probable incidence
      of lung cancer. The author used a linear multistage model, a Poisson model and a
      Cox proportional-hazards model; the magnitude of the risk from occupational
      exposure to concentrations equal to MAC values (0.04 mg/m3) was different for
      each model and it accounted for 9.02 x 10(-3), 2.04 x 10(-2) and 4.68 x 10(-2),
      respectively. Each of these values exceeded the acceptable level of the risk from
      occupational exposure which usually falls within 10(-3).

PMID- 9198716
TI  - [Eosinophil cationic protein in persons with contact allergy to disinfectants].
AB  - The concentration of eosinophil cationic protein (ECP) in blood serum was
      determined in 53 health service workers (women) with contact allergy to
      disinfectants and in 16 healthy women using a radioimmunological method. The mean
      ECP concentration in the study group accounted for 7.518 micrograms/l, and in the
      control group 4.893 micrograms/l. The concentration of 8.403 micrograms/l (the
      mean concentration in the control group + 2 SD) was taken as a cut off
      concentration value. In 17 (32.1%) persons with contact dermatitis, pathological
      ECP values were found. An increased ECP was observed in persons with positive
      results of prick test, especially in the case of Dermatophagoides, pollens and
      latex as well as in those with increased total IgE concentration. Our results
      indicate the involvement of immediate allergy in the incidence of contact allergy
      to disinfectants.

PMID- 9198717
TI  - [Exposure to ceramic fibers in the work environment. III. occupational exposure
      to ceramic fibers in plants which produce and apply insulation materials made of
      ceramic fibers].
AB  - The study was aimed at assessing the exposure to dust in the work environment of
      plants which produced and apply packing and insulation materials made of ceramic
      fibres. The study revealed that workers were exposed to dust containing
      respirable ceramic fibres and in some cases (production of packing cord,
      insulating tape and paperboard) respirable asbestos fibres. The mean
      concentration of respirable fibres ranged from 0.05 to 0.62 f/l cm3, and
      concentrations of total dust fell between 0.6 and 23.2 mg/m3. The mean
      concentrations of respirable fibres were usually below (0.5 f/l cm3 for
      respirable ceramic fibres with asbestos mixture; 1 f/cm3 for respirable ceramic
      fibres), and of total dust much higher (1 mg/m3 and 2 mg/m3, respectively) than
      MAC values proposed. The initial dermatological examinations (25 workers) allow
      the conclusion that contact with ceramic fibres induces in some workers acute
      dermatitis and dermal papilla.

PMID- 9198718
TI  - [Analysis of education processes in areas of public health and occupational
      medicine. Introductory premises and hypotheses].
AB  - In the first section of the work the premise encouraging the analysis of
      educational systems in the areas of public health and occupational medicine is
      presented. There is an urgent need for the education of highly personnel in these
      two fields, and the adhering of educational systems to the current needs requires
      an in-depth historical and sociological analyses as well as the evaluation and
      comparative studies. The model analysis and the research hypothesis are subject
      of the two other sections.

PMID- 9198719
TI  - [Identity of the occupational medicine physician].
AB  - The author identifies three meanings contained in the term "occupational
      medicine': medical research, the system of health care and a separate medical
      specialisation. The main interest is focused on the third meaning: occupational
      medicine as a medical specialisation and thus its basic concepts are discussed
      and defined. The scope of knowledge and skills as well as the kind of practical
      activities which endow occupational medicine with features which justify its
      significance as to be separated from other medical disciplines and to become a
      medical specialisation are indicated. Effective preventive programmes for the
      populations at risk of health impairment due to occupational exposure to harmful
      factors and to unsatisfactory working conditions are mentioned by the author as a
      basic criterion which distinguishes occupational medicine from other medical
      disciplines.

PMID- 9198720
TI  - [Problems associated with setting maximum allowable concentrations (MAC) of
      harmful substances present in the work environment].
AB  - The major aim of setting MAC values is to reduce the risk of occupational
      exposure to harmful substances to the acceptable level. In the process of setting
      MAC values, a critical analysis of the toxicological and medical literature, used
      by teams of experts who try to estimate the probability of health effects with
      different concentrations and different duration of exposures, is most essential.
      This process is usually very difficult since the epidemiological data and the
      results of animal experiments are often incomplete, and extrapolation of
      experimental results from animals to humans entails a lot of doubts. Moreover,
      one never knows which level of the risk can be considered as acceptable. That is
      why MAC values set by groups of experts cannot be treated as absolutely safe to
      the human health. They should be verified if new data on biological effect of
      substances harmful to health and new criteria for occupational risk assessment
      become available.

PMID- 9198721
TI  - [Environmental factors which impair male fertility].
AB  - Introduction of new technologies involving many chemicals does not remain free
      from the effect on the human health. Occupational acute poisoning is rare now-a
      days, but we often face many problems arising out of the late sequel to
      exposures, such as mutations, neoplasms or reproduction disorders. Numerous
      research institutes of occupational medicine are involved in the evaluation of
      the effect of environmental factors on the workers' health. Many recent
      publications emphasise that the quality of the human semen is gradually
      decreasing which is manifested by the lower number of spermatozoons (1 cm3)
      semen, a higher proportion of morphologically impaired spermatozoons and a higher
      per cent of motile spermatozoons. The quality of the semen is affected not only
      by the hazards present in the general environment, but also by the factors
      occurring in the work environment. Occupational exposure induces sometimes
      infertility of couples but more often impairs the reproduction, and this is one
      of important issues which be addressed by occupational medicine.

PMID- 9198722
TI  - [Chemical accidents and catastrophes as a source of the greatest hazard to the
      environment and human health in Poland].
AB  - The author presents sources of the greatest chemical hazards to the environment
      in Poland, among which industry and transport occupy the first two places. The
      availability of data and information on chemical hazards to the environment and
      the human health are discussed. Legislation, organisation and competences of
      institutions designed to prevent and mitigate the outcomes of chemical disasters
      are outlined. It was found that in Poland a possible danger of chemical disasters
      with serious consequences for the people and environment does really exist.
      Certain industrial installations as well as road and railway transport belong to
      the major threats. Among chemicals, ammonia, chlorine, sulphur dioxide and
      phosgene are considered as most dangerous. In Poland the Ministry of Internal
      Affairs and the Ministry of Environmental Protection, Natural Resources and
      Forestry are legally responsible for prevention and mitigation of the outcomes of
      chemical disasters.

PMID- 9198723
TI  - [Combination therapy in diuretic resistance].

PMID- 9198724
TI  - [Direct thrombin inhibitors].

PMID- 9198725
TI  - [Percutaneous therapy of kidney calculi. Current status].

PMID- 9198726
TI  - [Vectors for gene therapy].

PMID- 9198727
TI  - Brimonidine--an alpha 2-agonist for glaucoma.

PMID- 9198728
TI  - Pentosan for interstitial cystitis.

PMID- 9198729
TI  - [Discitis in childhood: integrated neuroradiological imaging in diagnosis and
      follow-up study of one case].
AB  - Discitis is an inflammatory disease of the intervertebral disc which has usually
      a benign evolution in childhood. It often recognizes an infectious etiology.
      Still discussed however is the possibility of a primitive discal involvement (not
      secondary to a vertebral inflammation) or of a non infectious etiology and the
      subsequent more correct diagnostic-therapeutic procedures. We report a case of a
      girl with discitis diagnosed early and treated with antibiotics and orthopedic
      corset, whose follow-up shows a benign evolution. We underline the importance of
      modern neuroradiological imaging: in particular, MR plays a major role in the
      inflammatory diseases of the column, both in diagnosis and in follow-up. MR scans
      of the involved disc allow frequent controls without radiogenic risks and with a
      good resolution because of the multiplanarity typical of the method.

PMID- 9198731
TI  - [Perinatal issues of diabetes in pregnancy].

PMID- 9198730
TI  - Dexfentluramine in the treatment of juvenile obesity.
AB  - BACKGROUND: The aim of this study was to investigate the potential of
      dexfenfluramine (dF) for reducing cardiovascular risk factors and improving
      compliance towards diet in a group of young patients hospitalized for essential
      obesity of high degree (BMI > or = 35). METHODS: 103 adolescents (mean age 15.4
      +/- 0.2) participated in a nine-week randomized double-blind study of dF (15 mg
      bid) versus placebo. All patients received a VLCD (2,512 kJ/day = 600 kcal/day)
      for two months. In basal conditions, and after 30 and 60 days of treatment,
      anthropometric variables (height, weight, BMI, and W/H) and cardiovascular risk
      factors (blood glucose concentration, total cholesterol, HDL-cholesterol,
      triglycerides, systolic and diastolic blood pressure) were monitored.
      Modifications in hunger and satiety were also assessed. RESULTS: During the
      treatment period, both the dF group and the placebo group presented a similar
      pattern of weight loss (BMI = dF: 36.7 +/- 0.5 vs 32.5 +/- 0.4 vs 30.1 +/- 0.4;
      placebo: 37.0 +/- 0.6 vs 33.1 +/- 0.5 vs 30.8 +/- 0.5). No important side-effects
      were recorded in either group. Blood pressure and metabolic markers decreased
      significantly in both groups. Earlier reductions in total cholesterol and
      diastolic blood pressure in dF-treated subjects were the only significant
      differences observed as compared to the patients receiving placebo (day 30 =
      total cholesterol: 120 +/- 2 (dF) vs 132 +/- 3 (placebo) mg/dI; p < 0.005;
      diastolic blood pressure: 73 +/- 1 (dF) vs 77 +/- 1 (placebo) mmHg; p < 0.01).
      However, after 60 days, these values were similar in the two groups. As far as
      non-parametric data are concerned, dF determined a reduction in hunger and an
      increase in satiety in a significantly higher number of subjects than did the
      placebo, not only after 30 days of treatment (92.8% vs 55.3% and 92.8% vs 45.5%,
      respectively; p < 0.0001), but also after two months of treatment (97.8% vs 67.4%
      and 97.8% vs 45.8%, respectively; p < 0.0001). CONCLUSIONS: These findings
      demonstrate that dF represents a useful support in the treatment of juvenile
      obesity and might ensure a better individual compliance towards restrictive
      diets, particularly in the initial "critical" stages, in the absence of important
      side-effects.

PMID- 9198732
TI  - [Psychopathological aspects in a group of children and adolescent with insulin
      dependent diabetes mellitus].
AB  - BACKGROUND: We have studied a group of children and adolescents with IDDM to
      evaluate their personality features and family relationship to point out elements
      of psychopathological risk or evident mental disorders. Our study group is
      composed of 30 subjects (age range 7-19 years) with IDDM for at least one year.
      METHODS: The methods employed were interviews to patients and their parents for
      the attitude towards the illness (done separately), Rutter scale for parents, an
      anxiety scale for children and adolescents (Busnelli) and a questionnaire about
      knowledge of diabetes (GISED). In the interviews with parents anamnestic data
      were collected with particular attention to early symptoms of mental disorder.
      Metabolic control was tested by the HbA1c measure using high pressure column
      chromatography, in the same laboratory. RESULTS AND CONCLUSIONS: On the basis of
      different results we divide our study group into three subgroups. The first (30%)
      present no mental disorder or at least reactive or transient disorder. The second
      subgroup (57%) show mild mental disorder. The third subgroup (13%) present severe
      mental disorder. In the first subgroup the adaptation to the illness was good,
      because of a normal personality, absence of past psychological disorders and good
      family relations. The second subgroup show a wider variability of symptomatology
      and 65% of these patients had some behaviour disorder in their past, which became
      more evident after diabetes onset. In the third subgroup diabetes seems to worsen
      pre-existing status of mental disorder. Metabolic control is better in the first
      subgroup than in the other two subgroups which do not differ too much one from
      the other. In conclusion, the better family relationship and personality history
      a patient had, the better adaptation to illness and metabolic control he had (1st
      Subgroup). The 2nd subgroup seems to be particularly at risk because it shows
      behaviour disorders and risk for future personality disorder. In the 3rd subgroup
      mental illness was already present even if not diagnosed at the onset of diabetes
      and needs to be treated anyway. As a matter of fact, it seems possible that the
      chronic illness points out and fixes perhaps pathological characteristics already
      present, which did not emerge until the traumatic onset of diabetes.

PMID- 9198733
TI  - [Nutritional needs of the preterm infant after hospital discharge].
AB  - The authors report their experience in the Division of Neonatology of the
      Catholic University of Rome about the choice of milk alimentation and mineral and
      vitamin supplementation before discharge and during the subsequent follow-up,
      with particular reference to very low-birthweight preterm infants (< 1500 g).
      Basing on empirical experiences, the authors emphasize the importance in current
      practice of post-conceptional age, with special regard to the kind of milk to
      choose after discharge and the time and terms of the weaning. Furthermore they
      stress nutritional, immuno-allergic and psychological advantages of human milk
      before and after hospital discharge, particularly related to the presence of long
      chain polyunsaturated fatty acid (LCP), recently known to be essential on retina
      and brain development in the preterm infant. When breast milk is not available,
      the authors confirm the efficacy, before discharge, of preterm infant formulas
      and subsequently of infant formulas and after of follow-up formulas. The authors
      hope that the directions proposed by the American Academy of Pediatrics in 1983
      will be modified in order to recommend cow-milk only after the first year of life
      of the infant. They finally suggest specific mineral and vitamin supplementations
      (iron, calcium, phosphorus, fluoride; vitamins K, D, E and folic acid), to be
      started after hospital discharge.

PMID- 9198734
TI  - [Ectopic neuroglial tissue associated with intrapulmonary congenital cystic
      adenomatoid malformation].
AB  - BACKGROUND: Few cases of ectopic neurological tissue have been reported in the
      lung. The aim of the present study was to give a brief overview of these cases
      and to examine an additional case of intrapulmonary neuroglial heterotopia. We
      have identified only sixteen similar cases in the literature. CASE DESCRIPTION:
      The object of our study was a male fetus of Asian parents at the 23rd week of
      gestation, in which ultrasound tests revealed the presence of anterior
      encephalocele. Routine postmortem examination of lung samples showed neuroglial
      tissue and a congenital adenomatoid cystic malformation of type II. The lesion
      was made up of multiple small cysts lined with columnar or ciliated cuboidal
      epithelium. A possible link between adenomatoid malformation and intrapulmonary
      neurological tissue has not so far been reported in the literature.
      Immunohistochemical analysis showed the presence in the pulmonary parenchyma of
      neuronal cells (neuron-specific enolase positive), astrocytes (glial fibrillary
      acidic protein positive) and intra-alveolar squamous cells (citokeratines
      positive), indicative of fetal aspiration of amniotic fluid. CONCLUSIONS: There
      are several possible explanations for the presence of intrapulmonary neuroglial
      heterotopia: fetal aspiration, neural crest migration defects or vascular
      embolization with implantation. However, in the view of the microscopic findings
      and at the same time recognizing the intrapulmonary aspiration of amniotic fluid,
      the authors maintain that the most likely explanation for the heterotopia is that
      of consequential multiple malformations. Moreover neuroglial ectopy and cystic
      adenomatoid congenital malformation of the lung could have appeared
      simultaneously, due to embryologic insult between the 4th and the 20th week of
      gestation.

PMID- 9198735
TI  - [The interdisciplinary approach and early surgery in the trigonocephaly].
AB  - Craniofacial surgery aims to stop the pathological process due to the presence of
      one or more malformations affecting this part of the body, in order to prevent
      and reduce the secondary damage caused by wrong development of the stricken
      structures. However, in order to achieve this goal, it is necessary to abide by
      some criteria, like the interdisciplinary nature of therapeutic procedures and
      early surgery. Since craniofacial malformations affect some anatomical areas that
      need combined approaches for diagnosing, preventing and correcting the existing
      anomalies or the possible complications, it is extremely necessary to set a
      collaboration between different medical and surgical disciplines. Surgical
      "timing", lasting from 4 to 6 months, is the basis of early surgery, which aims
      to prevent the morphostructural alterations of the part, assuring again the
      physiological growth of the stricken tissues. For this reason, craniostenosis are
      the malformation syndromes that mainly fit this kind of therapeutic protocol. In
      this document the authors describe the application of the above cited principles
      for the resolution of the stenosis of the metopic suture in 9 patients (3 males
      and 6 females), admitted to the Department of Maxillofacial Surgery of the
      University of Rome "La Sapienza".

PMID- 9198736
TI  - [Susceptibility testing of fluconazole: evaluation of a multicenter study of the
      working group "Clinical Mycology" of the German Speaking Mycological Society].
AB  - In a collaborative study for in vitro testing of fluconazole against clinical
      yeast isolates participated 21 laboratories of the working group "Clinical
      Mycology" of the German Speaking Mycological Society. In these centers, according
      to a standard test protocol 1181 clinical isolates from 1033 patients were tested
      to their susceptibility against fluconazole by microdilution, agar diffusion and
      partly by agar dilution. Approximately 600 strains (59.1%) of the collective of
      1106 isolates sent to a reference center underwent retesting in one laboratory
      (center 13). These strains demonstrated almost the same species distribution as
      the total collective. For 80% of all isolates a MIC of < or = 4 micrograms/ml and
      for 90% of the Candida albicans strains a MIC of < or = 2 micrograms/ml has been
      determined. Only approx, 9% of all isolates (4% with Candida albicans) showed a
      MIC of < or = 25 micrograms/ml. By parallel testing of 10 control strains issued
      by the reference center to the laboratories, the inter- and intra-laboratory
      comparability of the susceptibility testing of fluconazole was checked. The
      results demonstrated that under appropriate technical prerequisites and
      standardised test conditions, the methods used routinely in bacteriology
      microdilution, agar dilution and agar diffusion may also be applied in a
      reproducible way in the routine mycological laboratory for the susceptibility
      testing of yeasts.

PMID- 9198737
TI  - [Fluconazole: advances in the testing of sensitivity of yeasts. 28th Session of
      the Clinical Mycology Study Group of the German-Speaking Society of Mycology.
      Illertissen, Germany, 26-27 April 1996].

PMID- 9198738
TI  - [Criteria for a microdilution susceptibility testing method of fluconazole:
      proposal of a standardized testing method for yeasts].
AB  - For the proposal of a standardised susceptibility testing method of yeasts
      against fluconazole the laboratory experiences of the last years and the results
      of a collaborative study of 21 laboratories from Germany and Austria were
      compiled. The present paper reflects the work flow and gives advice for
      performing the microdilution method.

PMID- 9198739
TI  - [In vitro susceptibility testing of Candida species against fluconazole using the
      microdilution test with Alamar Blue].
AB  - The investigation of susceptibility of Candida species to fluconazole was
      performed in microdilution to a supplemented HR-medium. The sufficient
      reproducibility of the test was verified using special control isolates and
      isolates of patients. The excellent applicability of the method in routine
      diagnostics was evaluated by in vitro testing of susceptibility of 279 Candida
      isolates from patients being colonised or suffering from endomycoses. The Candida
      species showed different susceptibility against fluconazole: 96% of the C.
      albicans isolates were sensitive, 55% of the C. glabrata isolates had a reduced
      sensitivity, and 26% were resistant against fluconazole (MIC > 25 micrograms/ml).
      C. krusei isolates were highly resistant (9 of 11 strains).

PMID- 9198740
TI  - [Controversies in the standardization of susceptibility testing on yeasts to
      azole antimycotics].
AB  - Due to the different physical-chemical conditions of the therapeutical azoles it
      is necessary to choose an adequate testing procedure. In the group of azoles
      caused by its hydrophilia fluconazole susceptibility testing can be handled
      easily. However it is not possible to take the same test conditions for
      itraconazole as for fluconazole due to the extreme high hydrophobicity of
      itraconazole. The current recommendations of NCCLS should be considering these
      problems. Therefore it is necessary to standardize susceptibility testing for all
      azoles possible.

PMID- 9198741
TI  - [Susceptibility testing of yeasts against fluconazole: proposal for a
      standardized agar diffusion method with 25 microgram fluconazole paper discs].
AB  - This paper gives a proposal for a standardised agar diffusion susceptibility
      testing method with 25 micrograms fluconazole discs. The methodology compiles the
      results of several years of work to develop a reliable and reproducible routine
      method for the microbiology laboratory. In this proposal, in addition, the
      critics and experiences of a collaborative study for susceptibility testing of
      fluconazole with 21 laboratories from Germany and Austria are included.

PMID- 9198742
TI  - [Susceptibility testing of yeasts against fluconazole: comparison of the Etest
      method with microdilution and agar dilution].
AB  - In bacteriology, the Etest has a broad field of application in bacteriology and
      is recently available for the antimycotics fluconazole and itraconazole. By means
      of the presence of gradient concentrations of the active substance on the carrier
      material, it is possible to obtain reproducible MICs of the antimycotic
      substances. The results of susceptibility testing of 326 clinical yeast isolates
      with the Etest were compared to those MICs obtained by microdilution and agar
      dilution. A 100% concordance of the MIC markers (mode-, MIC50- and MIC90-value,
      standard deviation of the mean log2-MIC-dilution steps) was given when compared
      by a +/- 1 MIC-dilution step range with microdilution and by +/- 2 MIC-dilution
      steps with agar dilution; species dependent all strains were within 2 x standard
      deviation of the individual MIC-mean of the species. By comparison of the
      individual MIC-values maximum differences of +/- 6 MIC-dilution steps were
      obtained, where 70% of all results were within +/- 2 MIC-dilution steps, and more
      than 92% of all strains were within +/- 3 MIC-dilution steps. The Pearson's
      correlation coefficients show a good agreement of the Etest with microdilution (r
      = 0.92) resp., agar dilution (r = 0.88) demonstrate, however, clearly
      insufficient correlations (r < 0.65) to the reference methods, for species with
      difficult to read Etest inhibition zones (e.g., Candida glabrata, Candida krusei,
      Candida parapsilosis). The differences between the proposed test methods
      recommended by the NCCLS and the working group "Clinical Mycology" of the German
      Speaking Mycological Society (AG-KMYK) are tabled.

PMID- 9198743
TI  - [Fluconazole and itraconazole susceptibility testing with clinical yeast isolates
      and algae of the genus Prototheca by means of the Etest].
AB  - Preliminary own results suggest, that the Etest (produced by AB BIODISK, Solna,
      Sweden) performed on casitone medium meets the requirements of a routine test of
      yeast susceptibility to fluconazole and itraconazole. Testing of 46 clinical
      yeast isolates, of 5 strains of Exophiala dermatitidis and 4 strains of algae of
      the genus Prototheca revealed species-, genus- and strain-specific variations of
      the susceptibility to fluconazole and itraconazole. Candida glabrata was less
      susceptible to both triazoles than the other Candida species with exception of
      Candida krusei. Exophiala dermatitidis was highly susceptible to itraconazole.
      Prototheca wickerhamii and P. zopfii were resistant to both triazoles. Casitone
      medium is most appropriate for the determination of susceptibility to fluconazole
      and itraconazole by the Etest. The results of the Etest were comparable with
      those of a breakpoint test (microdilution method).

PMID- 9198744
TI  - [The Etest--an alternative to the NCLLS standard for susceptibility testing of
      yeasts?].
AB  - The Etest and the NCCLS method are not much differing in respect to their
      reproducibility. Only single observations exist on the clinical correlation of
      both tests. The correlation between both tests are known as being dependent on
      the yeast species and antifungals used. Due to the easy and simple handling the
      Etest is attractive for routine laboratories. The Etest has to be more evaluated
      before it can be generally recommended. The NCCLS method also is not validated
      until now. Different test methods should be compared thoroughly with the above
      mentioned standard.

PMID- 9198745
TI  - [Comparison of three antifungal susceptibility testing methods for the in vitro
      testing of Candida isolates from patients with HIV infection].
AB  - The MIC values of fluconazole were determined for 96 Candida isolates (56 C.
      albicans, 15 C. glabrata, 9 C. krusei and 10 C. tropicalis). The methods employed
      for antifungal susceptibility testing were: microdilution according to the
      protocol M27-P of the NCCLS (M 27-Pmicro) using RPMI 1640 medium or HR medium
      following Troke & Pye (HRmicro) as well as the agar diffusion method by means of
      the Etest (YNB agar). The in vitro results were compared with the clinical
      outcome of patients. All C. albicans isolates received from AIDS patients with
      fluconazole-refractory candidosis showed MICs of > or = 6.25 mg/ml (M27-Pmicro)
      or > or = 25 mg/ml (MRmicro) and Etest). On the other hand some MICs of C.
      albicans isolates from AIDS patients with fluconazole-sensitive candidosis were
      also beyond these breakpoints. Therefore, a possible success of a fluconazole
      therapy cannot unequivocally be predicted from the MIC value determined in vitro.

PMID- 9198746
TI  - [Fluconazole: comparison of pharmacokinetics, therapy and in vitro susceptibility
      of yeasts].
AB  - Fluconazole penetrates well into the tissues and body fluids which were examined
      and achieves rapid equilibration between the different compartments. The
      pharmacokinetics of fluconazole are independent of the dose after oral or
      intravenous administration. This finding, together with the drug's slow
      elimination (t1/2 30 h) facilitate the estimation of the therapeutically
      effective dosage. The concentrations of fluconazole measured in blood can be
      extrapolated to the concentrations in tissue (lung, brain, gynecological
      tissues), body fluids (sputum, saliva, vaginal secretions) and exudates. The
      concentration of fluconazole in cerebrospinal fluid and in the vitreous humour of
      the eye is ca. 80% of that in blood. Fluconazole is predominantly excreted in the
      urine in the unchanged form, which explains the 10 to 20 fold higher
      concentration of the drug in urine relative to blood. Although this
      pharmacokinetic profile favours the use of fluconazole in mycotic infections of
      the urinary tract it also means that the dose of the drug may have to be adapted
      to lower regimens in the systemic treatment of patients with restricted kidney
      function. The in vitro and in vivo susceptibility of the yeasts correlates with
      the concentrations of fluconazole measured in the different compartments of the
      body.

PMID- 9198747
TI  - [Plasma and tissue concentrations of fluconazole: discussion of the breakpoint
      problem].
AB  - The reliable prediction of the clinical outcome during antifungal therapy is an
      issue of paramount priority in clinical research, since there are no appropriate
      parameters available. MIC values and in the future breakpoints may serve as
      surrogate criteria if further standardization of in vitro antifungal
      susceptibility testing especially for fluconazole leading to improved
      interlaboratory reproducibility of the test results can be provided. With
      reproducible susceptibility testing methods for Candida species now being
      available, tentative fluconazole interpretative breakpoints derived from MICs
      determined by the NCCLS M27-T broth macrodilution methodology are now open for
      public commentary. Besides the proven susceptibility of the fungus, clinical
      response to antifungal therapy with fluconazole also depends to a great extent on
      the daily dosage and the corresponding plasma and tissue concentrations as well
      as the immunological status and the underlying disease of the patient. The
      promising results of a relatively small number of dose finding studies with
      fluconazole in non-neutropenic patients indicate that with daily doses up to 1000
      mg/die higher clinical response rates compared to those under lower dosages can
      be achieved. In view of future valid breakpoints, higher corresponding plasma and
      tissue levels of fluconazole should be achieved on which the therapeutic success
      depends substantially. However, this simplified concept needs several
      adjustments. Misinterpretation of MIC values and breakpoints may have as a
      consequence that patients with often life-threatening fungal infections may not
      be treated with an efficacious and better tolerated agent.

PMID- 9198748
TI  - Immunotherapy for asthma.

PMID- 9198749
TI  - Immunotherapy for asthma.

PMID- 9198750
TI  - Immunotherapy for asthma.

PMID- 9198751
TI  - Immunotherapy for asthma.

PMID- 9198752
TI  - Immunotherapy for asthma.

PMID- 9198753
TI  - Immunotherapy for asthma.

PMID- 9198754
TI  - Immunotherapy for asthma.

PMID- 9198755
TI  - A prediction rule for community-acquired pneumonia.

PMID- 9198756
TI  - A prediction rule for community-acquired pneumonia.

PMID- 9198757
TI  - The epidemic of cardiovascular disease in Eastern Europe.

PMID- 9198758
TI  - Risk of stroke after myocardial infarction.

PMID- 9198759
TI  - Risk of stroke after myocardial infarction.

PMID- 9198760
TI  - Restrictive cardiomyopathy.

PMID- 9198761
TI  - Restrictive cardiomyopathy.

PMID- 9198762
TI  - Olfactory dysfunction in multiple sclerosis.

PMID- 9198763
TI  - Insomnia.

PMID- 9198764
TI  - [A 'suppository for vomiting prevention'].
AB  - Three children, a girl aged 9 and two boys aged 2.5 and 6 years, presented with a
      stiff neck and fever. They had been treated for vomiting and diarrhoea with among
      other drugs metoclopramide or domperidone suppositories. As a result
      extrapyramidal signs had developed. These were cut by intravenous injection of
      biperiden. It is argued that gastroenteritis in children should be treated by
      oral rehydration only and that there is no place for antiemetics.

PMID- 9198765
TI  - [Unfounded doubt in laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy began to gain ground in the late eighties. The
      smaller incision led to less postoperative pain and faster recovery. By now, the
      method has become a matter of controversy: the laparoscopic operation took more
      time than the 'minilaparotomy'. This criticism can be refuted: laparoscopy gives
      faster recovery than the conventional large incision and a better view than the
      'minilaparotomy'.

PMID- 9198766
TI  - [What to do with surgically removed tissues: send it to the pathologist or put it
      in the medical waste container?].
AB  - Clinicians are sometimes in doubt whether or not to send routinely removed tissue
      to the pathologist, as not every pathological investigation produces relevant
      findings. It is not easy, however, to select specimens to be investigated. The
      cost effectiveness of pathological examination should be investigated
      prospectively in relation to other clinical diagnostic procedures, e.g. if it is
      decided that it is not cost effective to take biopsies during endoscopy, it may
      be questioned whether the endoscopy itself is cost effective.

PMID- 9198767
TI  - [Treatment of essential hyperhidrosis using thoracoscopic high dorsal
      sympathectomy].
AB  - Essential hyperhidrosis (EH) is a little-known disorder which may have a strong
      adverse effect on the patient's functioning. Conservative treatment of EH is
      often disappointing and the 'classical' surgical treatment is very radical and
      complicated. Thoracoscopic sympathectomy is efficacious in the treatment of
      palmar (and axillary) EH.

PMID- 9198768
TI  - [Activated charcoal as first-choice therapy in poisoning].
AB  - In gastrointestinal detoxication, three methods are possible: ipecac induced
      emesis, gastric lavage and administration of activated charcoal. The method of
      treatment predominantly used in the Netherlands is gastric lavage in combination
      with activated charcoal. Published evidence suggests that activated charcoal not
      preceded by gastric emptying is preferred. Additional advantages of using
      activated charcoal alone as the method of choice for gastrointestinal
      decontamination are patient friendliness, low cost and time saving because quick
      intervention by general practitioners is possible.

PMID- 9198769
TI  - [Little clinical relevance in routine pathological examination of uteri removed
      in women with prolapse symptoms].
AB  - OBJECTIVE: To study the clinical usefulness of pathological examination of the
      uteri removed from women with complaints of prolapse of the uterus. DESIGN:
      Retrospective study. SETTING: Department of Obstetrics and Gynaecology and
      Department of Pathology of the Medical Centre Alkmaar, the Netherlands. METHODS:
      Between June 1st 1990 and August 31st 1994, 221 women underwent vaginal
      hysterectomy because of prolapse of the uterus. At the SIG Zorginformatie
      national reference data were collected from the pathology archives (PALGA).
      RESULTS: No malignancy or carcinoma in situ of cervix or endometrium was found in
      the 221 women; 7 times a cervical intraepithelial neoplasia (CIN) 1 with free
      hysterectomy resection margins was seen. In the national data of 5,739 comparable
      operated women a malignancy was found in 9 (0.16%) patients while 10 (0.17%)
      specimens showed a carcinoma in situ; in one of these cases an adenocarcinoma of
      the endometrium had not been removed completely in the area of the fallopian
      tube. The unexpected finding of a cervical or uterine malignancy at histological
      examination is extremely rare (1:717 hysterectomies nationwide) if the uterus was
      surgically removed because of prolapse. CONCLUSION: The idea of omitting
      histological examination under certain conditions needs further evaluation. A
      prospective study should ascertain under what circumstances, e.g. the combination
      of a normal menstrual bleeding pattern, or absence of postmenopausal bleeding,
      with a normal cervical smear preoperatively, and normal macroscopic appearance,
      judged by the pathologist, microscopic examination can safely be omitted.

PMID- 9198770
TI  - [Complication rate in laparoscopic cholecystectomy not different for residents in
      training and surgeons].
AB  - OBJECTIVE: To assess the difference in safety of laparoscopic cholecystectomy
      performed by residents and staff surgeons. SETTING: St. Antonius Hospital,
      Nieuwegein, the Netherlands. DESIGN: Retrospective study. METHOD: Results of 649
      laparoscopic cholecystectomies performed by staff surgeons experienced in
      laparoscopic surgery, by residents under supervision of a staff surgeon, by
      residents without supervision and by inexperienced surgeons, were compared.
      RESULTS: Patients were comparable, except for liver function disorders and raised
      sedimentation rates, of which there were more in the group operated by the non
      supervised residents, compared with the staff surgeons. Average operation time
      was 57 minutes in all four groups. Non-supervised residents had more retained
      stones than staff surgeons (19 vs 6%) and reported more bleeding during surgery
      than staff surgeons (21 vs 8%). Conversion rate was the same (3.9%) in all four
      groups. Complications occurred in 5.7%; this also was the same in the four
      groups. CONCLUSION: Residents following a traditional surgical training without
      practice on animals, perform laparoscopic cholecystectomy as quickly as and with
      the same conversion and complication rates as their teachers.

PMID- 9198771
TI  - [Experiences with outpatient laparoscopic cholecystectomy].
AB  - OBJECTIVE: To determine the feasibility and desirability of laparoscopic
      cholecystectomy in day care. DESIGN: Prospective, pilot study. SETTING: Academic
      Medical Centre, Amsterdam, the Netherlands. METHOD: Fifteen patients (ASA I/II
      according to the American Society of Anesthesiologists) with symptomatic
      gallstones underwent laparoscopic cholecystectomy with the intention to discharge
      them the same day. Data were collected about: pain (visual analogue scale); pain
      medication before and after discharge; (rc)admissions; consultations of general
      practitioner or day care centre; complications; satisfaction of the patients
      about this treatment modality. RESULTS: Fourteen patients could be discharged
      after 6.2 hour (standard deviation 1.2) of observation. The pain scores and
      medication use were low. Readmissions did not take place and there were no
      consultations of general practitioners or the day care centre. These patients had
      no complications. Thirteen of them preferred day care over admission in hospital.
      One patient was admitted because of colicky pains and a common bile duct stone
      was diagnosed, which was removed endoscopically. CONCLUSION: Laparoscopic
      cholecystectomy in day care appears feasible in patients with symptomatic
      gallstones and no functional incapacities if day care facilities are present.

PMID- 9198772
TI  - [Allergy to human semen].
AB  - Two women aged 29 and 27 years, with complaints ranging from itching and swelling
      during or after cohabitation to anaphylactic symptoms comprising generalized
      urticaria, angioedema and dyspnoea, were found to be allergic to human semen. The
      total amount of serum IgE had increased in both, and the amount of semen albumin
      specific IgE in one of them; both showed a positive reaction to an intracutaneous
      test with seminal plasma. The women were given a course of hyposensitization
      treatment, after which the problems disappeared.

PMID- 9198774
TI  - ['I see, I see what you don't see' (body dysmorphic syndrome].

PMID- 9198773
TI  - [Identification of disadvantaged areas; a system for resource allocation to
      family practitioners].
AB  - OBJECTIVE: To develop a method for the identification of underprivileged areas in
      the Netherlands for resource allocation to general practitioners. DESIGN:
      Literature review and analysis of national data. SETTING: All postal codes in the
      Netherlands. METHOD: Definition of requirements of the method, selection of
      required data and calculation of deprivation scores. RESULTS: The method
      developed includes an index, based on income and number of people receiving
      income from benefit schemes, calculated for very strongly urbanized areas.
      Overall 87 four-digit postal codes were identified as underprivileged areas in
      which 875,000 people live. About one in three inhabitants of the four largest
      cities is living in such area. CONCLUSION: For the first time in the history of
      Dutch health care a national method for the identification of underprivileged
      areas was developed. This method was adopted as a basis for making enhanced
      payments to general practitioners for patients living in these areas. Taking into
      account the availability of relevant data, the method developed is the most
      feasible at this stage, but it is not yet perfect. This is especially true for
      medium sized cities. Therefore, further validation and refinement of the method
      are needed.

PMID- 9198775
TI  - [Antibiotics in otitis media with effusion].

PMID- 9198776
TI  - [50 years after Manfred Bleuler. What do we know today about late-onset
      schizophrenia(s)?].
AB  - Since Manfred Bleuler's description of the clinical picture of late onset
      schizophrenia over 50 years ago, debate has persisted as to whether it is
      justifiable to differentiate this as a valid, independent entity from the group
      of classic schizophrenic disorders with early onset. As this review shows, this
      question cannot be answered unequivocally even now. It must rather be remarked
      that we have neither been able to decisively extend our knowledge since Manfred
      Bleuler's comprehensive contribution, nor managed to achieve a much sounder basis
      methodologically. The reasons for this are the international conceptual and
      terminological confusion that has developed around this illness group, and on the
      other hand the methodological limitations of the empirical studies conducted on
      this clinical picture so far.

PMID- 9198777
TI  - [Impulsiveness and impulse control. On the psychological and psychopathological
      conceptualization].
AB  - Impulsiveness and impaired impulse control are connected with an increasing
      number of psychic disorders. While impulsiveness presents an enduring, pervasive
      predisposition of personality, the DSM-IV category of "impulse control disorder
      not elsewhere classified" is operationalized by specific dysfunctional behaviors.
      So far, the construction of impulsiveness has really not been sufficiently
      clarified. What does it means and how can one describes it. Different means of
      conceptualization are presented from a psychological and psychopathological point
      of view. Their critical review leads to the hypothesis that impulsiveness
      subsumes a specific quality of drive, on the one hand, which is closely related
      to a person's temperament and control mechanisms on the other. Drive and impulse
      control represent enduring traits that act on all levels of personality function,
      including behavior, cognitive processing and affect regulation. Finally, a model
      of impulsiveness is suggested that reflects the close interactions among drive,
      affect and cognition in the regulation of behavior.

PMID- 9198778
TI  - [Historical and current principles of the design of psychiatric clinics].
AB  - At the beginning of the 19th century, institutional care for the insane was
      established by the various German states. At first, the separation of curable and
      incurable patients influenced psychiatric care and the construction of hospitals.
      The combination of care and cure in one hospital in Illenau was a turning point
      in institutional care. Contradictory tendencies characterized the second half of
      the 19th century: the integration with general medicine in the cities, on the one
      hand, the social separation and cure in the seclusion of the countryside, on the
      other. The characteristic psychiatric construction in different countries was
      influenced by individual architects. The following building styles were dominant:
      in England, panoptic architecture; in the United States, linear staggered
      structures; in France, the "carres isols"; and in Germany, the structure of
      blocks with cross-axes. At the end of the 19th century, the system of pavilions
      was internationally accepted; occupational therapy and mental care in the
      countryside were introduced. From the First World War until the end of the 1960s,
      a standstill in psychiatric buildings was noted in Germany, and institutional
      care came under increasing criticism. There was a reorientation from the middle
      of the 1970s as a result of more effective therapeutic possibilities. A variety
      of complementary institutions, outpatient and partly inpatient therapies, which
      were recommended by the "Psychiatrie-Enquete", started to be realized. Smaller
      units and different models of integration of psychiatric care, such as building
      the hospital next to a general hospital or psychiatric wards within a general
      hospital, became relevant criteria for planning the construction of psychiatric
      hospitals, as did the integration into the community and the city. Principles of
      organization like the construction of a communicative quiet inner room, or
      grading the rooms from public to private, were structurally integrated. Specific
      structural requirements for the construction and design of psychiatric hospitals
      should be evaluated in more detail by post-occupancy methods.

PMID- 9198779
TI  - [Are self-perceivable neuropsychological deficits in patients with neuroses or
      personality disorder diagnoses indicative of later schizophrenia?].
AB  - For the first time, the present study assessed the achievable predictive value of
      early self-experienced neuropsychological deficits for the fater development of
      schizophrenia. Ninety-six patients with DSM-III-R diagnoses mainly of the
      formerly neurotic or personality disordered field, of whom 81% had shown such
      basic disorders at the time of the index examination and therefore were
      classified as persons at high risk of developing schizophrenia, were re-examined
      for schizophrenia. After an average follow-up period of about 8 years, more than
      half of the re-examined sample had developed a schizophrenic disorder according
      to DSM-III-R. The outcome of schizophrenia versus no schizophrenia was predicted
      correctly in 77% of cases by the presence or absence of self-experienced
      disturbances of perception, thought, speech or action.

PMID- 9198780
TI  - [Validity of assessment of schizophrenic basic symptoms].
AB  - A study on the concept and measurement of the basic disorders of schizophrenia is
      presented. A total of 151 male adult psychiatric inpatients (51 with a dual
      diagnosis of schizophrenia and alcoholism, 50 schizophrenics and 50 alcoholics)
      were included. The aims of this study were: (1) the replication of the previous
      finding that the Frankfurt Complaint Questionnaire (FBF) contains items that
      discriminate between schizophrenia and alcoholism; (2) an empirical comparison
      between FBF and the Bonn Scale for the Assessment of Basic Symptoms (BSABS); (3)
      testing the relationship between basic and negative versus positive symptoms, as
      measured by the Positive and Negative Syndrome Scale (PANSS). Regarding (1), the
      former result was replicated. Regarding (2), FBF subscales and BSABS categories
      were shown to be significantly but weakly related, even if identical symptoms
      were included in the inquiry. Regarding (3), FBF and BSABS were found to be more
      closely related to negative than to positive PANSS items. Theoretical
      implications and consequences for further research are discussed.

PMID- 9198781
TI  - [Event-related potentials in semantic speech processing by schizophrenic
      patients].
AB  - Event-related potentials (ERPs) can be used for high-resolution mental
      chronometry. For about 15 years, this method has been applied to the study of
      linguistic phenomena. Semantic incongruency produces a negative component at
      about 400 ms after stimulus onset, the N400. We measured the N400 component in 20
      schizophrenic patients and 20 normal control subjects performing a lexical
      decision task in which semantic distance between prime and target was varied. The
      results provide evidence of dysfunctional semantic information processing in
      schizophrenic patients, and reaction time data from previous studies can be
      interpreted within an electrophysiological framework. The N400 amplitude and
      latency data support recent spreading activation models of schizophrenic language
      dysfunction.

PMID- 9198782
TI  - [Structural affinities of the incomprehensible in schizophrenic delusion].
AB  - Schizophrenic delusion constitutes a fictive reality of its own; moreover, it
      transforms the originally experienced psychotically incomprehensible into a
      structure of meaning. It is assumed that the incomprehensible is reified in the
      actual delusion by means of structural affinities. Reciprocally, it is through
      these structural affinities that we can approximate hermeneutically to the
      characteristics of psychotic existence.

PMID- 9198783
TI  - [Multi-axial system of chapter V (F) of ICD-10. Initial results of a multicenter
      practicability and reliability study].
AB  - With the introduction of operationalized diagnostic systems the multiaxial
      approach became a more important issue. The proposed multiaxial system of ICD-10
      consists of three axes: on axis I psychiatric diagnoses are made according to the
      ICD-10 Clinical Guidelines or Diagnostic Criteria for Research. Axis II
      (Disability Diagnostic Scale, DDS) deals with impairment of psychosocial
      functioning. On axis III environmental/circumstantial and personal lifestyle
      management factors are rated. As part of the WHO international field trial,
      applicability and inter-rater reliability of the system were examined in seven
      German-speaking centers. In addition axis II was compared with the corresponding
      axis of DSM-III-R (Global Assessment of Functioning Scale). 45 German clinicians
      rated 12 case histories written in English (provided by WHO) with 488 ratings
      altogether. Diagnoses on axis I with an average percentage agreement of 65.6% and
      a mean kappa of 0.50 showed a moderate inter-rater reliability. For axis II the
      intraclass coefficient was 0.62, and that for the corresponding DSM-III axis was
      0.65: both these axes thus also had a moderate inter-rater reliability. There was
      a close correlation between the subscales and the global assessment of axis II
      there was. Wide variation was found in the psychosocial circumstances on axis
      III, the mean kappa value being 0.16. In the discussion proposals for the
      revision process for the multiaxial ICD-10 system are made.

PMID- 9198784
TI  - [Dimensional structure of the German version of the Brief Psychiatric Rating
      Scale (BPRS)].
AB  - Since the early 1960s the Brief Psychiatric Rating Scale (BPRS) has been one of
      the most frequently used standardized methods in international psychiatric
      research. The BPRS is used mainly for the rating of psychopathological symptoms
      of schizophrenic subjects. According to the results of factorial analyses, the
      original version of the BPRS is divided into five subscales, which have been
      preserved in the German translation. The validity of this original scale
      structure for the German BPRS version has not been investigated, however. A
      principal-components analysis of the 18 BPRS items carried out on the data of 301
      schizophrenics yielded four factors that are comparable with four of the original
      subscales: Thought disturbance, Hostility/suspiciousness, Anxiety/depression, and
      Anergia. These results are compared with earlier findings and similarities and
      differences are discussed.

PMID- 9198785
TI  - [Central to decentralized admission to the psychiatric hospital. Effects of
      changed admission circumstances on structure and process quality].
AB  - The study provides empirical data to compare different systems used for hospital
      admission procedures in a psychiatric clinic. The Psychiatric University Clinic
      Basel replaced its traditional central admission ward by direct admission to a
      number of different treatment settings. This change had consequences for both
      structural and procedural quality. More admissions occurred after prior notice
      had been given, and these admissions occurred more often at a time of day when
      more clinic staff were available. The rate of voluntary admissions increased, and
      the continuity of care, as measured by the number of transfers within the clinic
      during the first 5 days post-admission, was improved. These findings, which
      support an interpretation that the treatment conditions were improved, must be
      balanced against the drawback of delayed decision-making processes with, for
      example, longer waiting times for the patient. However, the continuity of
      therapeutic relationships can be increased through further changes in the
      procedural quality.

PMID- 9198786
TI  - [Psychosocial characteristics and attitudes of clients of day care centers and
      contact and counseling facilities].
AB  - Within the last 20 years, many day-care centers (Tagesstatten = TSn) and drop-in
      centers (Psychosoziale Kontakt- und Beratungsstellen = KBSn) have been set up in
      Germany. Although these institutions are widespread, there are hardly any
      empirical studies on the characteristics of their users or on their effects. In
      this study, 100 patients in TSn and KBSn in Berlin were examined. Social
      characteristics, psychopathology and attitudes of the patients were investigated.
      Almost all patients had been in psychiatric hospitals before. The current
      psychopathology varied greatly and was moderate on average. Two-thirds of the
      patients were pensioners, most of them living alone with just a few or no
      friends. Contact with other people and structured day activities were most often
      mentioned as positive aspects by the patients. The most frequent negative aspect
      was annoyance by fellow users. Patients in TSn were significantly younger and had
      higher scores on BPRS subscale anergia. In other variables, there was little
      difference between patients in the two institutions. The results suggest that
      both institutions--as intended--care for chronic mentally ill patients with poor
      social integration. For these patients they provide some compensations for a
      insufficient social network. Limitations and consequences of the findings are
      briefly discussed.

PMID- 9198787
TI  - [Early and differential diagnosis of 1,000 patients examined in a memory clinic].
AB  - The results from 1000 patients included in a consecutive sample of older persons
      showing signs of "age-related memory deficits" clearly demonstrate the necessity
      for a wide spectrum of differential diagnostic competence. The patients included
      in the study were diagnosed in succession by an interdisciplinary team of
      psychiatrists, neurologists, geriatric medical specialists, psychologists and
      gerontologists. The diagnostic process for clarification of DSM-III-R and ICD-10
      criteria are discussed in detail. In all, 49.6% of the patients were diagnosed as
      suffering from dementia of the Alzheimer type, 31% from vascular dementia and 10%
      from a mixed form. In all, 12.5% of the patients were somatically ill and 31.4%
      displayed other psychiatric conditions, 50% of which were evaluated as being
      treatable with psychotherapy. The results are primarily discussed for their
      relevance to the reality of current treatment.

PMID- 9198788
TI  - [Coincidence of Huntington chorea and epilepsy].
AB  - We report on a patient suffering from epilepsy and severe personality changes.
      Huntington disease was diagnosed by molecular-biological investigation. Clinical
      characteristics are discussed on the basis of modern concepts of the genetic
      mechanism. Neuroradiological investigation revealed marked cerebellar atrophy,
      while typical findings of Huntington disease, such as caudate nucleus volume
      loss, were lacking. The cerebellar atrophy could be attributable either to long
      term phenytoin-medication or to the pathological process itself.

PMID- 9198790
TI  - [Meeting report].

PMID- 9198789
TI  - [Transcranial magnetic stimulation. A diagnostic means from neurology as therapy
      in psychiatry?].
AB  - Transcranial magnetic stimulation (TMS) has been used since a decade to
      investigate the central motor system in the neurological routine diagnostic. From
      this experience TMS has proved to be a save and well tolerated procedure. In the
      past few years several studies investigated TMS to electrically stimulate deeper
      brain regions to find antidepressive effects in analogy to electro convulsive
      therapy (ECT). This could be of great advantage as TMS is well tolerated and does
      not require general anesthesia. There have been some case reports and also some
      controlled clinical studies on TMS as a therapeutic tool. The results of these
      studies have been promising. Many questions regarding technical and clinical
      aspects remain to be answered. In the future however TMS could be a valuable
      addition in the treatment of depression.

PMID- 9198791
TI  - [Borderline disorder and schizophrenia].

PMID- 9198792
TI  - Social play in juvenile rats after in utero exposure to morphine.
AB  - Changes in analgesia, play behavior, sexual behavior and responsiveness to stress
      and stimulants have been reported in rodents treated in utero with opiates.
      During development the endogenous opioids and opioid receptors are present in a
      tonic balance in the mammalian nervous system. The development of this balance is
      particularly sensitive to prenatal administration of opioid agonists and
      antagonists. The motivational and rewarding aspects of play behavior are probably
      controlled by endogenous opioid systems; low doses of opioids stimulate play
      behavior, whereas administration of opioid antagonists attenuates play behavior.
      We have analyzed the effect of morphine administration during the prenatal
      development of endogenous opioid systems on play behavior in juvenile rats. The
      doses of morphine used neither affected gestation of pregnant mother rats nor
      sensorimotor development of the juvenile rats. Levels of social play were
      elevated in juvenile rats after prenatal exposure to morphine. Social behaviors
      not related to play and non-social activities were not affected by the prenatal
      treatment procedure. To study these changes in more detail, social play was
      investigated using a sequential analysis in prenatally morphine-and saline
      exposed pairs. The sequential structure of behavior was not altered by the in
      utero exposure to morphine. Quantitatively, increases in behavioral transitions
      were found between behaviors related to play. The prenatal morphine treatment did
      not affect transitions between behaviors not related to play. It is concluded
      that the prenatal exposure to morphine did not affect mechanisms underlying play
      behavior itself, but is probably affecting more general phenomena like reward or
      motivation to play.

PMID- 9198793
TI  - [Current technologies in orthopedics].

PMID- 9198794
TI  - [New approaches to 3D-ultrasonographic imaging of infant hips].
AB  - Ultrasound of the infant hip is an established method in the diagnosis and
      monitoring of the treatment of congenital dysplasia of the hip (CDH). Its use as
      a screening method for CDH, early diagnosis and start of therapy results in a
      high success rate and reduces the length of the therapy. According to Graf's
      technique, the examination findings are taken from a standard plane. Assessment
      of the examined hip joint is based on information obtained from this standard
      intersection plane, which has to be representative for the whole joint
      configuration. Furthermore, the method according to Graf requires a very expert
      examiner. We report on a new approach to three dimensional ultrasound of the
      infant hip for covering and demonstrating the complete dimensions of CDH. A
      maturity disorder of the infant hip located outside the standard plane should be
      recognized by 3D ultrasound. In contrast to already existing 3D ultrasound
      systems with specially constructed transducers, we use a position sensor which,
      in conjunction with a video tape recorder, an external computer and the
      corresponding software, is able to support normal ultrasound equipment. A common
      7.5 or 5 Mhz linear transducer can be used. During the examination, the form and
      size of the femoral head is automatically analysed. The result is placed as a
      virtual sphere into the 3D data set. The quality of the examination should be
      independent of the examiner's skill.

PMID- 9198795
TI  - [Extracorporeal shock-wave therapy. Experimental basis, clinical application].
AB  - The purpose of our studies was to investigate experimentally the dose-dependent
      effects of extracorporeal shock waves on tendon and bone and to unveil
      therapeutic possibilities in tendinopathies and pseudarthroses. In animal
      experiments, both positive and negative influences were exerted by shock waves,
      depending on the initial situation and on the power of the applied shock waves.
      In prospective clinical trials positive effects were found in the treatment of
      persistent tennis elbow, plantar fasciitis, calcifying tendinitis, and
      pseudarthrosis. Our data show that extracorporeal shock waves may provide
      analgesic, resorptive and osteo-inductive reactions with nearly no side effects.
      However, the high cost of apparatus and staff prevents a routine application.
      Extracorporeal shock waves thus remain a last alternative before the indication
      is made for an operative procedure.

PMID- 9198796
TI  - [Single-image roentgen analysis for the measurement of hip endoprosthesis
      migration].
AB  - A method to determine migration of hip endoprostheses is described. Migration is
      measured by means of standard AP radiographs and therefore can also be evaluated
      in retrospective studies. Measurement is conducted in X-ray studies displayed on
      a computer screen. Enhancement of bony structures by application of filters is
      available. The developed software can be used with common commercially available
      computers and X-ray scanners, and does not require special hardware. Several
      methods to determine accuracy are described. The accuracy of the described method
      is about 1 mm (95% confidence limit), which compares favourably with other
      methods, but is less accurate than roentgen stereophotogrammetry. For other
      methods, accuracy was not determined adequately. Two years after implantation,
      revision within the first 10 years of follow-up can be predicted with a
      sensitivity and specificity of more than 80%.

PMID- 9198797
TI  - [Position identification in knee joint endoprosthesis].
AB  - In this paper we present a method for measuring the wear of the polyethylene
      inlay in knee joint endoprostheses from standard X-ray images. Our approach is to
      estimate the spatial position of the tibial and femoral components of the
      prostheses from their contours in the X-ray image. When we know the exact shape
      of these two components, we can calculate the minimal spatial distance between
      them which approximates the remaining thickness of the inlay. First results show
      that this approach might provide sufficient accuracy for the given task.

PMID- 9198798
TI  - [High definition roentgen technique. Alternative to or improvement of
      conventional roentgen technique].
AB  - X-ray images were taken of 22 patients suffering from different orthopaedic
      disease patterns using magnification with focus diameters between 0.012 and 0.100
      mm. This yielded improved resolution of detailed structures, especially in
      tumours and aseptic bone necroses. Owing to the relatively low efficiency of the
      X-ray tube (affected by the condition of the X-ray equipment), however, exposure
      times of several seconds were required, and the voltage had to be higher than in
      a conventional X-ray procedure. This resulted in a lack of sharpness owing to
      movement and a loss of contrast. Hence, the clinical use of focus diameters below
      0.1 mm does not seem to be meaningful.

PMID- 9198799
TI  - [Computer-guided robot-assisted hip endoprosthesis].
AB  - Computer-guided robot-assisted surgery in cementless total hip replacement
      requires exact preoperative planning at the 3D workstation Orthodoc. Only the
      Robodoc procedure allows the precise execution of the preoperative plan in
      surgery. Robot-assisted surgery has been undergoing clinical evaluation at the
      Berufsgenossenschaftliche Unfallklinik, Frankfurt, since November 1994. In all
      465 patients, the preoperative plan was successfully carried out
      intraoperatively. The high precision in reaming, leading to a superb bone implant
      contact, guarantees absolute initial stability and is likely to promote primary
      healing between implant and bone. The common and often published incidence of
      varus or valgus malpositioning and any fractures or fissures could be avoided
      through the use of Robodoc. Although immediate full-weight bearing was strongly
      recommended to the patients, no implant subsidence was seen in the treatment
      follow-up X ray studies.

PMID- 9198800
TI  - [Robot-assisted knee endoprosthesis].
AB  - With the development of powerful computer systems, computer-assisted medical
      diagnosis and therapy have become common over the last 10 years. Even in the
      surgical field, computer- and robotic-assisted techniques are becoming practical
      but are not yet used on a daily basis. In the orthopaedic field, computer and
      robotic assistance is used in planning and performing demanding three-dimensional
      osteotomies, setting pedicle screws in the spine and milling the femoral
      medullary canal in total hip replacement. This article introduces a computer- and
      robotic-assisted system for performing arthroplasty in total knee replacement
      procedures.

PMID- 9198801
TI  - [The use of lasers in surgical orthopedics. A current review].
AB  - In laser-assisted arthroscopic knee surgery, clinical outcome and experimental
      results are quite different. After laser treatment of local chondromalacia, large
      cartilage lesions with less tendency towards repair were more often seen than
      after conventional arthroscopic treatment. Therefore, laser treatment of
      chondromalacia cannot be recommended. Compared with conventional meniscectomy,
      laser-assisted meniscal surgery has some advantages, but there is also some risk
      of inducing gonarthrosis. Some studies show a good hemostatic effect of the laser
      and the feasibility of precise tissue cutting. On the other hand, laser treatment
      causes alteration of the tissue. The meniscal tissue becomes stiffer, which may
      promote the manifestation of gonarthrosis. Percutaneous laser disc decompression
      has been in successful clinical use since 1986 in the treatment of intervertebral
      disc prolapses. Studies of multiple orthopedic departments worldwide show a
      success rate of 75%. To guarantee the success the indications must be observed.
      The use of lasers in the arthroscopic treatment of outlet impingement syndrome
      have some advantages, too. The outcome is better than that of other arthroscopic
      techniques and there are fewer complications because of the hemostatic effect and
      the improved vision. Laser-assisted capsular shrinkage combined with arthroscopic
      labrum reattachment allows conventional laser use. Capsular shrinkage can be
      achieved with low-level laser energy. If this treatment is not successful, other
      operative techniques can be performed without restrictions.

PMID- 9198802
TI  - [Rapid prototyping. Construction of a model in the preoperative planning of
      reconstructive pelvic interventions].
AB  - X-ray or CT images allows only a limited three-dimensional orientation in
      presurgical planning. Especially for the planning of internal hemipelvectomies
      with custom-made endoprosthesis and for peri-acetabular osteotomies a high-grade
      orientation is necessary. This orientation is improved by a 3D CT-controlled
      manufactured 1:1 model of the pelvis. This enables and exact classification of
      defect and deformity, planning of resection planes, design of the suitable custom
      made implant and simulation of the operation technique as preoperative quality
      control.

PMID- 9198803
TI  - [Endoscopic treatment of intervertebral disk displacement. Percutaneous
      transforaminal access to the epidural space. Indications, technique and initial
      results].
AB  - The authors report their experiences with the percutaneous transforaminal
      approach to the epidural space. 85 patients were treated endoscopically for non
      contained lumbar herniated discs. Very good and good results of 20 patients
      (learning curve) were obtained in 65%. However, reoperation rate was 25% versus
      3% for the last 65 patients. The first 50 patients were treated under local
      anaesthesia, the last 35 patients under general anaesthesia. Operative technique
      is described in detail. Laser application in the epidural space is helpful for
      tissue ablation and to obtain hemostasis. No complications were observed. The
      main advantages of this new minimal invasive technique are, besides reduced
      morbidity, less epidural scarring and removal of the sequestered tissue under
      visual control while retaining disc tissue in the intervertebral space. Thus, the
      disadvantages of open nucleotomy with possible instability and abundant scarring
      may be avoided.

PMID- 9198804
TI  - [Perthes disease].

PMID- 9198805
TI  - [Asthma-like inflammation--a new term is needed].

PMID- 9198806
TI  - [Scandinavian guidelines for asthma. Nationalforeningen til Bekaempelse af
      Lungesygdomme].

PMID- 9198807
TI  - [The discovery of IgE and its importance for allergologists].
AB  - During the 30 years that IgE has been known the knowledge about allergy has
      improved immensely. We have now available reliable procedures for allergy
      diagnosis, standardised allergen preparations for diagnosis and treatment, an
      improved knowledge about mechanisms behind allergy and tests to monitor the
      efficiency of therapeutic procedures. New sophisticated procedures for modulation
      of IgE function and production are waiting around the corner. However, despite
      this increase in our knowledge the prevalence of allergic diseases is still
      increasing. More efforts must be dedicated to the understanding why an atopic
      individual is sensitised and how this sensitisation can be avoided by primary
      prevention.

PMID- 9198808
TI  - [Asthma or asthma-like condition?].
AB  - Asthma is currently seen as an inflammatory disease of the airways. The clinical
      characteristics are any of a variety of airway symptoms occurring in conjunction
      with bronchial obstruction (which is reversible on treatment with beta 2-agonists
      or steroids) and bronchial hyper-responsiveness. The symptoms can be triggered by
      a variety of factors and the clinical picture is not uniform. The most common
      differential diagnoses are chronic obstructive lung disease (COLD) and asthma
      like conditions unaccompanied by bronchial obstruction.

PMID- 9198809
TI  - [New drugs in asthma treatment. Leukotriene receptor blockers and leukotriene
      synthesis inhibitors].
AB  - Asthma is an inflammatory airway disease. The patient is characterised by
      increased mucus secretion, mucosal oedema, bronchial obstruction of varying
      degree and bronchial hyperresponsiveness. Several cell types and a large number
      of mediators are involved in asthma-related inflammation and constriction of the
      airways. The leukotrienes constitute an important group of mediators in asthmatic
      inflammation. The study of specific leukotriene receptor antagonists and
      biosynthesis inhibitors has not only shed light on the underlying mechanisms in
      asthma, but also opened up the way to new treatment alternatives. As zafirlukast,
      a leukotriene receptor antagonist has just been licensed in Finland, it is a
      suitable opportunity to review the importance of leukotrienes in asthma and the
      use of agents that affect them.

PMID- 9198810
TI  - [Qualitative methods in empirical health research. Focused group interview and
      participant observation].

PMID- 9198811
TI  - [Transfusion medicine--Scandinavian recommendations].

PMID- 9198812
TI  - [Authorization acknowledged in all of Scandinavia].

PMID- 9198814
TI  - Teenage kicks.

PMID- 9198813
TI  - [Apoptosis: cellular and clinical aspects].
AB  - Removal of damaged cells is essential for the maintenance of life in
      multicellular organisms. The process of self destruction, apoptosis, eliminates
      surplus or damaged cells as part of the pathophysiological defence system.
      Apoptosis is essential in structural and functional organogenesis during
      embryological development. The physiological regulation of tissue kinetics is a
      product of both cell proliferation and cell death. Internal and external
      regulatory stimuli regulate the balance between apoptosis and mitosis by genetic
      interaction. Apoptosis is characterized by condensation of chromatine as a result
      of DNA degradation, formation of blebs in the plasma and nuclear membranes,
      condensation of cytoplasma, formation of vesicular apoptotic bodies, and
      phagocytosis by neighbouring cells without inflammatory response. A number of
      observations indicate that programmed cell death plays an important role in the
      regulation of cytofunctional homeostasis and defense against accumulation of
      damaged cells, eg with DNA alterations. Dysregulation of the apoptotic gene
      program, eg by mutations, may not only lead to loss or degeneration of tissue,
      but also to hyperproliferative and tumorigenic disorders. New evidence indicates
      that apoptosis regulation is important both in aging processes and diseases such
      as: neuropathies, immunopathies, viral infections, cancer, etc. Pharmacological
      intervention designed to modulate apoptosis seems to raise new possibilities in
      the treatment of disease.

PMID- 9198815
TI  - Like a prayer.

PMID- 9198816
TI  - A poultry offering.

PMID- 9198817
TI  - Hepatitis C: it's in the blood.

PMID- 9198818
TI  - [Biotransformation of phenazone and sulfadimidine as markers of liver metabolism
      of drug and xenobiotic oxidation and acetylation in women with breast cancer].
AB  - The aim of our study was to determine phenazone pharmacokinetics as an index of
      hepatic microsomal enzymes activity and acetylation phenotype in women with
      breast cancer. Phenazone test was made in 41 women with breast cancer and in 25
      healthy women as a control group. Acetylation phenotype was measured in 40 women
      with breast cancer and in 25 healthy women as a control group. The plasma
      concentration of phenazone was estimated by the spectrophotometric method of
      Brodie and associates. Acetylation phenotype was determined by the Bratton
      Marshall method in Varley's modification. The mean phenazone half-life time
      (t0,5), shortened significantly and the mean elimination rate constant (K)
      increased in women compared with a group of healthy persons. Mean clearance rate
      was increased in women with breast cancer too, compared with a group of healthy
      women. Acceleration of phenazone elimination may suggest that in patients with
      breast cancer elimination of the other drugs metabolized by the pathway similar
      to phenazone also may be changed. This should be considered in selection of their
      dosage. We have observed the predominance of rapid acetylators in women with
      breast cancer comparing with healthy persons. This difference was not
      statistically significant. Our results of acetylation phenotype in women with
      breast cancer suggests that rapid acetylation may be a factor of susceptibility
      to breast cancer.

PMID- 9198819
TI  - [The effect of glucose and mannitol on transperitoneal transport; in vitro
      studies].
AB  - The changes of peritoneal absorption and excretion of urea, uric acid and
      gentamicin caused by glucose or mannitol have been analysed. These modification
      were differentiated, depended on the type of transported molecule, used osmotic
      agent and time of its activity as well as transfer direction. For example,
      glucose caused the increase of uric acid absorption and the decrease of urea
      excretion by about 40%. In contrast, mannitol didn't change the uric acid
      transport, but lowered the bidirectional transfer of urea. The mean values of
      gentamicin transport diminished after application of glucose or mannitol. This
      lowering was smaller in comparison with isoosmolar conditions. The reasons of
      above modifications are complex. It supposes that in vitro the direct physical
      action of hyperosmolality, metabolic activity of glucose and membrane effect of
      gentamicin balanced the solvent drag process. Furthermore, the heterogenecity of
      glucose and mannitol influence on the transperitoneal compounds transport are
      related to the transport rates (mechanism) of the examined osmotic agents and/or
      their metabolic activity.

PMID- 9198820
TI  - [Biostimulating laser therapy as one method of treating bone and joint diseases].
AB  - An assessment of medium power semi-conductor laser treatment effectiveness was
      evaluated in 205 patients (132 females and 73 males) aged 57 to 75 (mean 62.5)
      years with pain syndrome in a course of hip, knee, shoulder, elbow, temporo
      maxillaris and vertebral joints degenerative changes. Procedures were performed 3
      times a week using punctual technique, sweeping and scanning. Total number of
      procedures ranged from 8 to 20 and radiation energy dose was 4 to 12 J/cm2.
      Favourable therapy effect was demonstrated as pain and oedema disappearance in
      about 40% of patients; insignificant therapeutic effect was achieved in 46.3% and
      lack of affect in 13.7% of individuals.

PMID- 9198821
TI  - [Non-infectious complications during treatment with continuous peritoneal
      dialysis (CAPD)].
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is an established effective
      method of maintenance in patients with end-stage failure. Because of the
      increasing number of patients treated by this method it is essential to study
      complications of long-term CAPD, treatment which are connected with high
      intraabdominal pressure, peritoneal membrane response to non-physiological
      solutions and systemic metabolic changes.

PMID- 9198822
TI  - [The effect of magnesium on blood coagulation--state of the art literature review
      from 1959 to 1995].
AB  - The effect of magnesium on coagulation system is still an interesting subject for
      investigations. Shionoya in his publication (1927) reported for the first time
      possible inhibitory effect of magnesium on coagulation system. Since then, a
      large number of studies were undertaken to explain the mechanisms of influence of
      Mg++ on plasma coagulation, platelet function and fibrinolysis. In recent
      decades, the effect of magnesium on coagulation has led to controversy in a wide
      range of scientific publications. At present, series of experiments are
      undertaken in laboratories using modern methodology to evaluate the possible
      effect of magnesium on coagulation. The results of Anders's and Frisch's study
      reported here support the theory of the authors, who found no change in
      coagulation in the presence of physiological concentration of magnesium in blood
      serum. The influence on the final results, often contradictory, could have:
      different type of study (in vitro or in vivo), the object of the study (human
      being, animal), concentrations of magnesium (in most of cases non-physiologic and
      toxic) and out of date methodology. In majority of reported here studies there
      were no control groups, and clinical trials were not a double blind studies.

PMID- 9198823
TI  - [Current capabilities and procedures for diagnosing lung neoplasms].
AB  - Lung cancer is the most common malignant cancer in males and it's incidence is
      rapidly rising in females. Factors linked to this are associated with cigarette
      smoking, urbanization along with atmospheric pollution. The lack of success in
      the treatment of lung cancer has to do with in many cases late diagnosis at the
      stage when surgical treatment is not possible and radio and chemotherapy being of
      minimal effectiveness. The WHO has proposed the following classification of lung
      cancer: 1. Squamous cell carcinoma; 2. Small cell carcinoma; 3. Adenocarcinoma;
      4. Giant cell carcinoma; 5. Adeno-squamous cell carcinoma 6. Carcinoid. 7.
      Carcinoma of mucous gland. 8. Others. Early physical signs of lung cancer are:
      cough (50-80% of patients), dyspnea (10-15%), chest pain (15-20%), hemoptysis (20
      50%), recurrent pneumonia and bronchitis (30-50%). More serious clinical signs
      associated with growth of the neoplasm are hoarseness, pleural effusion, vena
      cava superior syndrome, and Pancoast's syndrome. The growing neoplasm secrets
      many biochemical substances, which are them activity passed on the bloodstream or
      make their way into the blood as a result of degeneration of the tumor. These
      substances may then be detected in the patient's plasma and act as markers of
      malignant disease. The characteristics of these markers is varied, e.g.:
      hormones, enzymes and tissue antigens. Methods used in the diagnosis of lung
      cancer which should be stressed, are apart from the obvious physical examination
      are chest x-rays, ultrasound, CAT scans, nuclear magnetic resonance, PET scans,
      and scintigraphy. Fine needle aspiration in changes in the peripheral regions,
      cytology of sputum, bronchial lavage, cytogenetic analysis. This underlines the
      need for prophylaxis, particularly the cessation of cigarette smoking.

PMID- 9198824
TI  - [Metastasis of clear cell carcinoma of the kidney to the thyroid gland].
AB  - We preset three patients operated on at our hospital with diagnosed metastasis
      clear cell carcinoma of the kidney to the thyroid gland 5, 6, and 9 years after
      nefrectomy. Patients were operated on because of nodular goiter and metastases
      were diagnosed intraoperatively (frozen section) at two cases and postoperatively
      in the remaining care (diagnosis made by pathologist-microscopic examination). A
      radical thyroidectomy was employed without chemio- or radiotherapy which is now
      recommended as a method of treatment of clear cell carcinoma metastasis.

PMID- 9198825
TI  - [Monoclonal gammapathy in a population of patients from the Regional Hospital in
      Dabrowa Tarnowska].

PMID- 9198826
TI  - [The inside story of the II edition of the History of Medicine by Wladyslaw
      Szumowski].

PMID- 9198827
TI  - [Evaluation of treatment outcome after nicergoline and pentoxifylline in patients
      with ischemic stroke].
AB  - The study has been taken up to compare the effect of treatment with nicergoline
      or pentoxifylline and typical treatment in early ischaemic stroke. The study
      included 121 patients aged 42-75, with the ischaemic stroke confirmed by CT scan,
      in early stage of stroke (within 24 hours after onset). Excluded from the study
      were patients with severe physical diseases. The patients were divided into three
      groups. Group I was treated typically, group II was given both typical treatment
      and nicergoline during 30 days, with a daily dose 8 mg i.v. within the first 5
      days followed by an oral delivery with a dose of 30 mg per day during the
      following 25 days. Group III had been profited from a typical, appropriate
      therapy and pentoxifylline delivery during 30 days as well, with a daily dose of
      1200 mg i.v. within the first 5 days followed by an oral dose of 800 mg
      subsequent days. The neurological state was assessed according to the European
      Stroke Scale (ESS), general fitness according to the Karnofsky Scale (KS) at the
      admission and after 30 days of the treatment. After 30 days of the treatment, no
      statistically essential differences between all study groups was found in: 1)
      mortality, 2) mean survival time, 3) neurological state, 4) patients general
      fitness. According to the above results the beneficial influence of nicergoline
      and pentoxiphylline treatment of ischaemic stroke was not confirmed.

PMID- 9198828
TI  - [Primary malignant lymphoma of the thyroid gland--diagnosis and treatment
      tactics].
AB  - The paper presents clinical signs, diagnosis, treatment and therapeutic results
      in the group of 10 patients with at primary malignant lymphoma of the thyroid
      gland. There were presented up to date methods of diagnosis and treatment with
      includes chemio- and radiotherapy. In authors opinion progress in imaging
      technics cyto- and histopathology, and potentiality of complex treatment allows
      us to avoid from surgery in most cases of malignant lymphoma of the thyroid.

PMID- 9198829
TI  - [Evaluation of the efficacy of treatment with exogenous thyroxin in patients
      after thyroidectomy].
AB  - The study was performed in 228 patients after thyroidectomy, including 101
      individuals permanently treated with thyroxin and 127 ones in whom treatment with
      thyroxin was started on the average 5 years after surgery. Control group
      consisted of 35 patients after thyroidectomy, average 2 years after surgery, not
      treated with thyroxin. Stump volumes and serum TSH concentrations were
      significantly higher in the patients who began treatment a long time after
      surgery (mean after 5 years) when compared with the control group (mean after 2
      years). It was proven that treatment with thyroxin led to significant decrease of
      the stump volume and to serum TSH normalisation. Treatment with thyroxin was
      successive in not all patients with nodular regrowth; in some of them despite
      using suppressive doses of thyroxin, progression of the lesions occurred, what
      claimed for different regrowth etiology. In spite of high serum TSH
      concentrations in 132 patients, only in 60 of them clinical manifestation of
      hyperthyroidism was observed. Treatment with thyroxin should be recognised as
      reasonable in prophylaxis and therapy of patients after thyroidectomy.

PMID- 9198830
TI  - [Relationship between the iron status of the pregnant woman and her body size and
      body composition before and during pregnancy].
AB  - For the analysis the relationship of the iron status of 86 pregnant women and
      size and composition body factors before and during pregnancy were made
      anthropometric, hematological and iron status indices. There were significant
      relations between pregestational body weight, height, body mass index and body
      weight, body composition in pregnancy and the values of iron status indicators in
      blood throughout gestation.

PMID- 9198831
TI  - [Incorrect caloric-nitrogen composition of parenteral nutrition solutions as a
      factor for causing liver damage--an animal model].
AB  - The experiment were carried out on 40, 3-week old rats who received solutions of
      aminoacids, glucose, fat, electrolytes, trace elements and vitamins. The ratio of
      non-protein calories to grams of nitrogen was: Group I-75:1, Group II-200:1,
      Group III-500:1. Control Group IV was on standard Murigan chow. The analysis
      included the following parameters: body mass, serum albumin concentration, GOT,
      GPT and ECH, and microscopic liver studies. The results show that body mass
      increases in Group I-III (7.5 g, SD 2.18; 1.45 g, SD 2.33; 1.85 g, SD 1.56
      respectively) were significantly lower when compared to the controls (11.6 g, SD
      2.72), with p < 0.001. Blood serum albumin concentration values were lower in
      Group I, II and III, and transaminase activity was elevated in comparison to the
      controls. Histological analysis showed mitochondrial damage and parenchymal
      degeneration with proliferation of Browicz-Kupfer cells in Group I and III
      animals, and no structural hepatic changes in Group II and in the controls. The
      results suggest a relationship between the above disturbances and the composition
      of the administrated solutions.

PMID- 9198832
TI  - [Fibroscopic bronchoscopy in intensive care].
AB  - The field of application for fibreoptic bronchoscopy (FB) in the intensive care
      unit has been extended since the generalised introduction of fibroscopes of 4.9
      mm in diameter (previously called paediatric fibroscopes). Paediatric and
      neonatal intensive care units have benefited from the availability in the market
      of these small endoscopes for 3.5 and 2.2 mm. The protected brush and alveolar
      lavage (LBA) enables a specific diagnosis to be made in bacterial pneumonia
      acquired during ventilation. The sensitivity of these techniques however is
      insufficient to be able to recommend their use as routine. Inversely, the FB with
      LBA remains a fundamental feature in the diagnosis of opportunistic infections in
      pneumonia. For the treatment of atelectasis, FB is overall not superior to
      physiotherapy. Aspiration with a fibroscope can however be recommended straight
      away in cases of alteration in blood gasses if cough is ineffective or if the
      atelectasis complicates endobronchial bleeding. The FB enables problems with
      difficult intubation to be resolved or for the positioning of probes. The
      conditions under which this is performed are more delicate than in routine
      anaesthesia (in cases of urgency, hypoxia). In the case of respiratory burns,
      tracheobronchial fracture and post intubation stenosis, FB enables both the
      diagnosis to be established and the level at which the lesion occurs. In
      paediatric intensive care, a fibroscope of 3.5 mm is used for performing LBA
      (opportunistic pneumonias), difficult intubation (facial dysmorphia), endoscopic
      diagnoses, in particular where there is a suspicion of an endobronchial foreign
      body, the assessment of unexplained dyspnoea (tracheal stenosis by vascular ring)
      and obstructive lesions. In neonatal intensive care, a fibroscope of 2.2 mm is
      used for difficult intubation and the localisation of lesions induced by
      ventilation.

PMID- 9198833
TI  - [Anorexia associated with bronchial cancer].
AB  - Anorexia is a frequent complaint in patients suffering from bronchial cancer. It
      is linked to multiple factors, organic, biological and psychological. The
      treatment of anorexia implies an involvement with all these factors. If it
      persists, it may be improved by corticosteroids or by derivatives of progesterone
      independently of the control of the tumour process.

PMID- 9198834
TI  - [Value of plasma D-dimer assays in the diagnosis of venous thromboembolism].
AB  - The diagnostic usefulness of measuring plasma D-dimers using the ELISA method and
      the latex agglutination test has been prospectively evaluated in 117 patients
      hospitalized for suspicion of acute venous thrombo-embolism (AVTE): pulmonary
      embolism was suspected in 80 patients and the remaining 37 had a suspicion of
      deep vein thrombosis of the lower limbs. The diagnosis of AVTE was confirmed in
      50% of the patients, all of whom underwent gold standard invasive investigation
      i.e. pulmonary angiography and/or contrast venography. The sensitivity,
      specificity, negative predictive value and positive predictive value of a D
      dimers plasma concentration exceeding 500 ng/ml for the diagnosis of AVTE were
      respectively 98, 58, 97 and 70% when using the ELISA method, and 86, 71, 84 and
      75% when using the latex assay. In 47 patients whose lung scans yielded
      abnormalities of indeterminate probability of pulmonary embolism, the sensitivity
      of the ELISA method was very high (94%), but that of latex assay was low (67%).
      Our results demonstrate that measuring the plasma D-dimers by the latex assay
      should not be used in the diagnosis of AVTE. On the other hand, the ELISA method
      might be of great interest in the diagnostic strategy of AVTE, as a normal
      concentration of D-dimers rules out almost definitely the diagnosis of AVTE, and
      hence, spares from performing invasive investigations.

PMID- 9198835
TI  - [Post hydatid chronic cor pulmonale].
AB  - We report a case in a patient aged 28 admitted with haemoptysis and dyspnoea. The
      chest x-ray showed multiple disseminated hydatid cysts throughout the lung
      fields. Computerized tomography and an abdominal echo found a hydatid cyst of the
      liver in contact with inferior vena cava which was probably responsible for the
      secondary pulmonary dissemination. Subsequently there was a multiplication of the
      lesions with rupture and infection of several cysts. After two years the disease
      progressed into chronic respiratory failure with the appearance of chronic cor
      pulmonale. The respiratory state rapidly worsened with several episodes of
      cardiorespiratory failure. Death occurred six months after the appearance of CPC.

PMID- 9198836
TI  - [Endovascular closure of a foramen ovale after a right pneumonectomy].
AB  - We report the case of a patient, 62-year-old, with a non small cell lung cancer
      treated by right pneumonectomy followed by chemo and radiotherapy. After surgery
      appeared a refractory hypoxemia increasing with supine position. Cardiac
      catheterism showed a right left shunt by reopening of the "foramen ovale". We
      have performed foramen's occlusion by endovascular method with prothetic material
      with good result until the death, 14 months later, by neoplasic evolution.

PMID- 9198837
TI  - [Severe bronchial stenosis with upstream bronchiectasis in an arc welder: causal
      relation or epiphenomenon?].
AB  - This case concerns an arc welder who presented suppurative bronchiectasis and
      episodes of purulent left side pleurisy in relation to cystic bronchiectasis of
      the left lower lobe and a very severe stenosis at the origin of the main left
      bronchus. The medicolegal problem was to assess the causal relationship between
      these lesions and occupational exposure. They do not come under the heading of
      table 44 of the General List and we made this the aim of discretionary award in
      front of a regional committee of compensation for occupational disease.

PMID- 9198838
TI  - [Pulmonary and musculo-cutaneous thigh actinomycosis].
AB  - We report a case of actinomycosis presenting with both a thigh abscess and a
      pulmonary lesion. Diagnosis was obtained by biopsy of this abscess, showing
      sulfur granules and further identification of Actinomyces israelii together with
      Actinobacillus actinomycetemcomitans in culture. Furthermore. Actinomyces
      israelii was isolated from bronchial secretions.

PMID- 9198840
TI  - [Dyspnea in a pneumonectomy patient].

PMID- 9198841
TI  - [Intense and rapidly progressive dyspnea].

PMID- 9198839
TI  - [Cushing syndrome and small cell carcinoma. Three case reports].
AB  - Paraneoplastic Cushing's syndrome associated with small cell carcinoma is a poor
      prognosis factor. Opportunistic infections are an important factor of morbidity
      and mortality. Therefore antiadrenal medications are necessary before initiating
      cytotoxic chemotherapy. The report of three recent cases will emphasize the need
      of special management of this disease.

PMID- 9198843
TI  - [Comments on methods and costs of disease management. Necessary research, but
      difficult].

PMID- 9198842
TI  - [New wave of chemotherapeutic agents: update in pulmonary oncology].

PMID- 9198844
TI  - [Primary pulmonary lymphoma].
AB  - There are three distinct clinico-anatomical entities today covered by the
      definition of a primary clonal pulmonary lymphoid proliferation. These are
      pulmonary lymphomas of B cell phenotype, of low grade malignancy, B cell
      lymphomas of high grade malignancy and finally lymphomatoid granulomatosis whose
      clonal characteristic is sometimes difficult to confirm. This general review aims
      to specify the pathophysiological, diagnostic, prognostic and therapeutic aspects
      of these different types. Low grade B cell lymphoma is the most common pulmonary
      lymphoma. Their development depends on mucosa associated lymphoid tissue. They
      are most often indolent and present as a chronic alveolar opacity. Their
      prognosis is excellent and the modalities of treatment are discussed (no therapy,
      surgery or monochemotherapy). High grade B cell pulmonary lymphomas are much
      rarer and may result from the transformation of a low grade lymphoma or arise in
      a particular situation such as imunodepression. Their prognosis is poor and the
      therapeutic possibilities depend most often on the underlying disease. The
      presence of lymphomatoid granulomatosis in this group of pulmonary lymphomas is
      debatable. The demonstration of a clonal character of this proliferation is
      practically never obtained and there is often extra pulmonary disease. The
      prognosis of this type of illness is extremely variable because certain studies
      have shown a cure using corticosteroids and cyclophosphamide whilst others have
      found that the disease is always fatal in spite of using strong polychemotherapy.

PMID- 9198845
TI  - [Hematopoietic growth factors and anti-infective respiratory defenses].
AB  - Colony-Stimulating Factors (CSFs) are a family of glycoproteins that are required
      for the proliferation and differentiation of hematopoietic progenitor cells.
      Among these factors, G-CSF and GM-CSF are principally involved in the production
      of neutrophils. They have been demonstrated to be effective in correcting
      neutropenia during cytotoxic chemotherapy or bone marrow transplantations. Beside
      their hematopoietic action, recent data indicate that G-CSF and GM-CSF also have
      stimulatory effects on mature neutrophils function. The functional properties of
      neutrophils that are enhanced by G-CSF and GM-CSF are those related primarily to
      the host's defense against microorganisms. For Gm-CSF those stimulatory effects
      also concern the macrophages. Investigations of several animal models of severe
      bacterial infection and specially pneumonia have indicated that exogenous
      recombinant G-CSF or GM-CSF can significantly enhance host defenses and improve
      rates of survival. Trials of recombinant G-CSF in combination with antibiotics
      for the treatment of severe pneumonia in noneutropenic patients have recently
      been initiated. First results confirm the good tolerance of recombinant G-CSF.
      Further prospective studies are required to determine the effectiveness and the
      conditions of administration of G-CSF and GM-CSF in this indication.

PMID- 9198846
TI  - [What is your diagnosis? Septic pulmonary embolism, right-sided pleural
      effusion].

PMID- 9198847
TI  - [Are diuretics still up-to-date?].

PMID- 9198848
TI  - [Pharmacology of potassium-sparing diuretics].
AB  - Potassium sparing diuretics in combination with thiazides represent a
      therapeutical enrichment if applied correctly that is with respect to
      contraindications, interactions (especially with ACE-inhibitors and AT1
      antagonists) and to pharmacokinetic properties. Triamterene has to be
      administered twice a day while amiloride and spironolactone are effective for 24
      hours. Of course, pharmacokinetic parameters of potassium sparing diuretics have
      to be considered also in fixed combinations.

PMID- 9198849
TI  - [The clinical spectrum of potassium-sparing diuretics].
AB  - The role of potassium-sparing diuretics in the treatment of hypertension is
      discussed. The results of two newer case-control studies showing both an
      increased risk for sudden cardiac death in patients receiving non-potassium
      sparing diuretics compared to those receiving potassium-sparing diuretics are
      presented. As a consequence of these studies thiazides should be given only at a
      low dose or in combination with a potassium-sparing agent. Data from several
      large intervention trials in elderly patients with hypertension show that
      treatment of high blood pressure with potassium-sparing diuretics is clearly
      beneficial since cerebral and cardiac events are both significantly reduced.
      Finally, potassium-sparing diuretics, especially spironolactone, play an
      important role in controlling high blood pressure in patients with primary
      aldosteronism. The presentation of a case report demonstrates, that development
      of resistance toward medical treatment may be due to elevated aldosterone levels
      and suppressed plasma renin activity and that the addition of spironolactone
      efficiently reduces elevated blood pressure values in this condition.

PMID- 9198850
TI  - [Significance of diuretics in the treatment of hypertension].
AB  - Due to new therapeutic substances the use of diuretics in the treatment of
      hypertension is decreasing slowly over the last few years. Nevertheless diuretics
      still represent one important cornerstone in the therapy of most forms of high
      blood pressure. Metabolic side effects of diuretics are often used as an argument
      against their clinical use. Indeed the diuretic therapy may lead as a function of
      the dosage and the duration of the therapy to an increase of total cholesterol
      and an impairment of the glucose tolerance. Spironolactone and other potassium
      sparing diuretics are "lipid-neutral". These metabolic side effects of the
      diuretics can be counterbalanced by the implementation of non-pharmacological
      means of blood pressure therapy. Body weight control seems to be of central
      importance. Therapy resistant forms of hypertension may be caused by many
      different pathogenetic mechanisms. Besides other reasons (such as secondary
      hypertension, non compliance ect) volume overload may represent one of the most
      important reasons of resistant forms of hypertension. Diuretics, especially also
      the aldosterone antagonists, play a central role in the control of most
      situations associated with volume overload in the setting of essential
      hypertension.

PMID- 9198853
TI  - [Are diuretics in the treatment of portal hypertension rational?].
AB  - When ascites develops in a patient with cirrhosis his probability to survive the
      following 2 years amounts to 50%. It is determined essentially by the residual
      functional capacity of the liver. In 80 to 90% of patients ascites due to portal
      hypertension can be managed by salt restriction and diuretics. Aldosterone
      antagonists are more efficient and have fewer side effects than loop diuretics.
      They may lower portal tension by an additional direct effect on the vasculature.
      A daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because
      (prerenal) renal failure may become a threat. If diuretics are insufficient or
      when a rapid therapeutic success is needed paracentesis of 4-6.1 is a safe option
      if intravascular volume is substituted simultaneously. Albumin has proven
      superior to other plasma expanders (protection of renal function, survival). Only
      in the few patients whose ascites is intractable by the forementioned measures
      should alternatives such as peritoneo-, venous or porto-systemic shunts (nowadays
      mostly by interventional techniques via a transjugular catheter) be evaluated.
      The only treatment which not only attacks ascites symptomatically but also
      corrects the underlying disease is liver transplantation.

PMID- 9198851
TI  - [Spironolactone: renaissance of anti-aldosterone therapy in heart failure?].
AB  - Mortality of patients with severe congestive heart failure (CHF) is still high
      despite combined treatment with angiotensin-converting enzyme (ACE) inhibitors,
      diuretics, and digitalis. Further therapeutic regimens are needed which include
      reversal of adverse myocardial remodeling and subsequent ventricular dysfunction.
      One third of all patients with CHF have diastolic left ventricular (LV)
      dysfunction with preserved systolic function. In these patients myocardial
      collagen matrix is the major determinant of myocardial stiffness and therefore
      diastolic function. Cardiac fibroblasts, expressing mRNA for types I and III
      collagens which are the major fibrillar proteins of the myocardial collagen
      network and for matrix metalloproteinase (MMP) 1 which is the key enzyme for
      interstitial collagen degradation, are controlled by the renin-angiotensin
      aldosterone (RAAS) system irrespective of hemodynamics and cardiac myocyte
      growth. In the rat with primary or secondary hyperaldosteronism, myocardial
      fibrosis occurs in the pressure overloaded, hypertrophied left and in the
      normotensive, nonhypertrophic right ventricle. In contrast, no fibrosis is found
      in either ventricle of rats with infrarenal aortic banding, when the RAAS is not
      activated, despite comparable systemic hypertension and LV hypertrophy. In
      cultured cardiac fibroblasts, either effector hormone of the RAAS, angiotensin
      (Ang) II and aldosterone (Aldo) stimulate collagen synthesis measured by 3H
      proline incorporation under serum-free conditions. Aldo is able to stimulate
      collagen synthesis normalized per total protein synthesis in a dose-dependent
      manner and at concentrations (10(-9) M) which are comparable to stimulated states
      in vivo (e.g., CHF). While Aldo does not affect collagen degradation AngII
      significantly inhibits, MMP 1 activity that would lead to further accumulation of
      collagen in the myocardium. Specific AngII type I or Aldo receptor antagonists
      are able to abolish the AngII or Aldo-mediated increase in collagen synthesis,
      respectively. In vivo in rats with primary or secondary hyperaldosteronism, the
      Aldo antagonist spironolactone has been shown to prevent myocardial fibrosis in
      both ventricles irrespective of the development of LV hypertrophy and
      hypertension. Thus, in vivo and in vitro evidence could be provided that the
      mineralocorticoid. Aldo, plays a pivotal role in promoting myocardial fibrosis
      and can be antagonized by its competitive receptor blocker, spironolactone. This
      may be of particular clinical relevance in treating patients with CHF where the
      RAAS is activated leading to myocardial fibrosis with subsequent deterioration of
      myocardial function. Clinical trials are needed to confirm these experimental
      data. If the ongoing RALES mortality study will prove that survival and/or
      morbidity of patients with CHF are improved by combined ACE
      inhibitor/spironolactone treatment a renaissance of anti-aldosterone therapy in
      patients with CHF would occur.

PMID- 9198852
TI  - [Diuretics in the treatment of heart failure: current pathophysiological
      aspects].
AB  - From a pathophysiologic point of view heart failure can be divided into systolic
      and diastolic dysfunction. Systolic dysfunction is characterized by a decreased
      ejection fraction and increased chamber volume which can be typically found in
      young people with congestive cardiomyopathy. Diastolic dysfunction is associated
      with an enhanced filling pressure but with a normal systolic pump function. This
      disorder can be typically found in elderly patients with myocardial hypertrophy.
      Treatment of congestive heart failure includes. 1.) reduction of central blood
      volume (preload reduction) 2.) decrease of peripheral resistance afterload
      reduction) 3.) regression of myocardial hypertrophy (improving myocardial
      stiffness) 4.) maintenance of atrial contraction (atrial kick) 5.) decrease of
      heart rate (prolongation of diastolic filling time and increase in contractility)
      6.) improvement of LV relaxation (positive lusitropic effect) and 7.) prevention
      of myocardial ischemia (improvement in contractility and relaxation). The primary
      goal of medical therapy is symptomatic improvement. Reduction in morbidity and
      mortality is only a secondary consideration. To achieve this goal ACE-inhibitors
      and in certain cases betablockers (cave: neg. inotropic action) are suited best.
      Additionally, digitalis-especially in the presence of atrial fibrillation- and
      vasodilators can be used to further improve quality of life. In the case of
      severe heart failure with or without atrial fibrillation oral anticoagulation is
      indicated to prevent systemic embolication. Diuretics are often used for
      symptomatic improvement but have no effect on long-term survival. Aldosterone
      antagonists (e.g, spironolactone) have a beneficial effect on LV remodeling and
      probably also on mortality. The role of endothelin antagonists and atriopeptidase
      inhibitors in the treatment of heart failure are not yet clear.

PMID- 9198854
TI  - [The hospice movement].

PMID- 9198855
TI  - [Symptom control and palliative care].

PMID- 9198856
TI  - [Pain treatment: current status and perspectives].

PMID- 9198857
TI  - [Delirium in palliative care].

PMID- 9198858
TI  - [Palliative and supportive care: at the frontiers of medical omnipotence].
AB  - Cancer patients have physical, social, spiritual and emotional needs. They may
      suffer from severe physical symptoms, from social isolation, spiritual
      abandonment, and emotions such as sadness and anxiety, or feelings of deception,
      helplessness, anger and guilt. In some of them, the disease is rapidly
      progressing and ultimately they die. Their demanding care evokes intense feelings
      in health care providers, the more since these incurable patients represent a
      challenge, which could be condensed under the heading "the challenge of medical
      omnipotence". We suppose that the way health care providers cope with these
      circumstances has a profound influence on the way these patients are cared for.
      The attitudes towards the emerging heterogeneous movement of palliative and
      supportive care and towards its different models of implementation can be viewed
      from this point of view. We try to demonstrate these interrelations and to
      discuss the danger that may arise if they remain obscure and unreflected.

PMID- 9198859
TI  - [Palliative care and pediatrics: between abandonment and desperation].

PMID- 9198860
TI  - [Palliative care and AIDS: support].

PMID- 9198862
TI  - [Palliative care. Education and interdisciplinary cooperation].

PMID- 9198861
TI  - [Euthanasia: a lame solution to a real problem].

PMID- 9198863
TI  - [Education in palliative care].

PMID- 9198865
TI  - [Spiritual support in palliative care. Emergence of a pastoral need between a
      religious crisis in society and the autonomic spiritual will in the patient].

PMID- 9198864
TI  - [Spiritual and religious support in palliative care: how to define it].

PMID- 9198866
TI  - [In the field. 1. Creating a need or waiting to be called?].

PMID- 9198867
TI  - [In the field. 2. Spiritual support of patients in the palliative stage in a
      university hospital].

PMID- 9198868
TI  - [A chaplain in a palliative care center: professional grief and resources].

PMID- 9198869
TI  - [Spiritual support: what physicians and caregivers say...].

PMID- 9198871
TI  - [Voluntary work experience in CESCO. Center for Continuous Care of the University
      Institute of Geriatrics].

PMID- 9198870
TI  - [Voluntary work. The need for initial and continued training of voluntary
      workers].

PMID- 9198872
TI  - ["Luciole"--ecumenical team for support of persons in the final stage of life at
      CHUV ].

PMID- 9198873
TI  - [Supporting life: an original experience for voluntary work].

PMID- 9198874
TI  - [Physiotherapists in palliative care are in the midst of transformation. Can
      these changes be encouraged?].

PMID- 9198875
TI  - [Palliative care and pediatrics. Management of a sick child at home: the
      Association Romande de Soins Pediatriques Specialises a Domicile].

PMID- 9198876
TI  - [Palliative care in a medico-social establishment].

PMID- 9198877
TI  - [Mobile team for palliative care in Geneva].

PMID- 9198878
TI  - [A palliative care center and approach to death in Valais: l'Antenne Francois
      Xavier Bagnoud].

PMID- 9198879
TI  - [Palliative home care in Tessin--an example: Lugano Hospice].

PMID- 9198880
TI  - [Developing a multidisciplinary support group for terminal care in the canton of
      Neuchatel].

PMID- 9198881
TI  - [The patient's turn to speak].

PMID- 9198882
TI  - [The patient's words].

PMID- 9198883
TI  - [Secondary prevention in patients before and after percutaneous transluminal
      coronary angioplasty: 5-year follow-up].
AB  - Several studies have demonstrated substantial risk reduction by risk factor
      modification in patients with established coronary artery disease. The number of
      studies investigating the implementation of risk factor intervention in clinical
      practice, however, is limited. We have, therefore, recorded drug use and
      cardiovascular risk factors in all 148 patients who had undergone percutaneous
      coronary angioplasty (PTCA) in 1989 at the University Hospital, Zurich, on
      hospital admission, after 6 months and 5 years later. Most patients had
      antithrombotic treatment with little change over time (78%, 87% and 83% on
      admission, after 6 months and after 5 years respectively, p = 0.27). The use of
      beta-blockers decreased moderately after 5 years (73%, 81% and 61% respectively,
      p < 0.01). Calcium channel blockers were used frequently without significant
      change in the follow-up period (56%, 50% and 46%, p = 0.25). Five years after
      PTCA, 91% of patients with a history of hypertension were on antihypertensive
      drugs. The use of lipid-lowering drugs increased markedly (5%, 16% and 33%
      respectively, p < 0.01). However, only a small proportion of patients qualifying
      for lipid-lowering drugs according to Swiss guidelines were treated. The
      proportion of current smokers decreased from 26% on hospital admission in 1989 to
      12% in 1994. We conclude that in our study population secondary prevention was
      generally satisfactorily implemented. However, better monitoring and treatment of
      increased lipid levels is mandatory.

PMID- 9198884
TI  - [Gastrin and its role in the development of ulcer disease].
AB  - Helicobacter pylori infected patients have increased gastrin release which shows
      a marked fall after cure of the infection. Recent studies indicate that
      inflammatory cells and cytokines play an important role in the pathogenesis of
      Helicobacter-associated hypergastrinemia. Views differ regarding the impact of
      gastrin on acid secretion. Current evidence suggests that gastrin is responsible
      for at least some of the increased acid secretion seen in duodenal ulcer
      patients.

PMID- 9198885
TI  - [Compulsory psychiatric drug therapy in Switzerland--legislation and reality
      exemplified by a few clinical cases].
AB  - We discuss the existing or desired legal basis for forced medical treatment in
      psychiatry, in the light of supranational, international and Swiss law. Four
      situations in which forced medical treatment may occur are described and
      illustrated with case reports. A distinction is drawn between treatment against a
      destructive will, treatment against lack of will, treatment against an antisocial
      will, and long-term treatment against a chronic destructive will. Finally,
      proposals for improved Swiss legislation on forced psychopharmacological
      treatment are discussed.

PMID- 9198886
TI  - [Increased cancer incidence in terminal kidney failure: potential pathogenetic
      mechanisms].
AB  - Increased incidence of cancer in various sites is observed in patients with end
      stage renal disease. A multitude of carcinogenic factors directly or indirectly
      associated with the disease may be involved. Impaired function of the immune
      system as well as impaired antioxidant defence, accumulation of carcinogenic
      compounds partly due to impaired renal elimination, and chronic infection and
      inflammation are found with increased prevalence in these patients and may
      contribute to enhanced tumor formation. Furthermore, factors associated with the
      dialysis treatment, such as bio-incompatibility reactions due to complement
      activating membranes, immunosuppressive medication in the course of prior
      unsuccessful renal transplantation, and impairment of DNA repair may also act in
      concert to accelerate malignant transformation.

PMID- 9198887
TI  - [Conservative therapy in thoracic outlet syndrome. Literature review and
      pathogenetic considerations].
AB  - Due to the broad clinical presentation and the lack of generally accepted
      diagnostic criteria, thoracic outlet syndrome (TOS) is a disputed diagnosis.
      Various surgical techniques have been described and investigated as treatment for
      TOS, whereas only a few studies have reported the outcome after a conservative
      approach. Based on the literature, the pathophysiology of TOS and the impact of
      conservative therapy are discussed. Our personal experience has shown that after
      early diagnosis and implementation this treatment is a safe and valuable
      therapeutical option in TOS based on the correction of a postural and functional
      disturbance of the upper thoracic aperture underlying the pathogenic process.
      Successful conservative treatment may also be considered as further diagnostic
      evidence for TOS.

PMID- 9198888
TI  - [Sudden death in hypertrophic obstructive and non-obstructive cardiomyopathy: can
      it be prevented?].
AB  - Sudden cardiac death constitutes the most devastating aspect of obstructive and
      non-obstructive hypertrophic cardiomyopathy. Loss of consciousness and family
      history of sudden cardiac death should alert the physician to the risk of sudden
      death. ECG, morphological and hemodynamic assessment, and exploration of central
      nervous activity are of little use in stratifying the risk of sudden cardiac
      death. Loss of consciousness associated with nonsustained ventricular tachycardia
      and inducible sustained ventricular arrhythmia identify patients at very high
      risk of sudden cardiac death. Nevertheless, many variable factors are involved in
      the pathophysiology of sudden cardiac death, and hence risk stratification of
      sudden cardiac death in patients with hypertrophic cardiomyopathy remains a very
      difficult clinical challenge.

PMID- 9198889
TI  - [Pneumocystis carinii pneumonia in a, until now, healthy 46-year-old HIV-negative
      man].
AB  - A 46-year-old male patient was referred from a peripheral hospital with a 5 days
      history of high fever, dyspnea and respiratory deterioration. Direct
      immunofluorescence examination of bronchoalveolar fluid repeatedly showed
      clusters of Pneumocystis carinii. High-dose sulfamethoxazole-trimethoprim therapy
      was initiated and the patient recovered promptly during the following days. This
      otherwise healthy patient's past history was unremarkable in terms of prior
      infectious diseases. There was no evidence of immunodeficiency and he was not
      taking medication. Antibodies against HIV-1 were repeatedly negative, as were the
      assay for p24-antigen, PCR for HIV-DNA and HIV culture. Subpopulations of
      lymphocytes showed normal values. Analysis of the IgG fractions revealed a
      decreased subclass 2 fraction. Functional assays showed decreased biological
      binding capacity of this subclass 2 IgG to polysaccharide antigens. A four-fold
      increase of cytomegalovirus (CMV) IgG titer suggested a concomitant CMV infection
      or reactivation. As CMV infection is known to cause transient cellular
      immunodeficiency, reactivated CMV infection, in concert with IgG subclass 2
      deficiency, could be a predisposing factor for P. carinii infection in this
      patient.

PMID- 9198891
TI  - [Aspiration of a wasp in the right lower lobe of the lung].

PMID- 9198890
TI  - [Pharmacotherapy of arteriosclerosis and its complications. Effect of ACE
      inhibitors and HMG-CoA-reductase inhibitors].
AB  - Atherosclerosis and its consequences account for most of the morbidity and
      mortality in Western countries. 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, knowledge on the cellular and molecular
      mechanisms of these cells and their alterations by cardiovascular risk factors
      and in atherosclerosis has greatly expanded. In particular, it has become clear
      that endothelial cells play a crucial role in the regulation of platelet
      function, coagulation, and vascular tone and structure. Interestingly,
      endothelial dysfunction occurs early, particularly if cardiovascular risk factors
      such as hyperlipidemia, hypertension and diabetes are present. This could lead to
      adhesion of circulating platelets and monocytes and increased accumulation of
      lipids in the intima, as well as increased contraction, migration and
      proliferation of vascular smooth muscle cells. One of the enzymes with a key role
      in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located
      on the endothelial cell membrane and is responsible for the conversion of
      angiotensin I into angiotensin II, as well as for the breakdown of bradykinin.
      While the antihypertensive effect of ACE inhibitors probably contributes to their
      antiatherogenic effects, other mechanisms are likely to be of greater importance.
      These direct antiatherogenic effects attributable to ACE inhibition are related
      to their vasculoprotective properties, including antiproliferative and
      antimitogenic activity, effects on endothelial function, protection against
      plaque rupture, antithrombotic effects, and possible antioxidant properties.
      There is overwhelming evidence to demonstrate the beneficial effects of long-term
      ACE inhibitor treatment in heart failure, acutely for suspected myocardial
      infarction (MI), and following MI in patients with left ventricular dysfunction.
      Hypercholesterolemia is a health risk, and epidemiological studies have shown a
      line between total cholesterol levels and the risk of cardiac events. Studies
      have shown that lowering the levels of total and low-density lipoprotein
      cholesterol using HMG-CoA reductase inhibitors can result in a decrease in
      cardiac morbidity and mortality. Angiographic studies of coronary arteries have
      demonstrated a disparity between the decrease in cardiac events and the extent of
      regression of coronary artery lesions. Mechanisms other than the regression of
      coronary stenosis may therefore be important in the beneficial effect of
      cholesterol lowering. It may be of major importance that lipid-lowering therapy
      is associated with improved endothelial function and decreased platelet activity.
      Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective
      properties which may explain their beneficial effects on cardiovascular morbidity
      and mortality.

PMID- 9198893
TI  - [Sentinel headache: a premonitory symptom too often unrecognized in intracranial
      ruptured aneurysm].
AB  - Headache is a common complaint in emergency departments, but only a small
      percentage of patients have a serious disease. Nevertheless, some forms of
      headache, such as "warning headaches", need special attention. By far the most
      common symptom associated with aneurysmal minor bleed (warning leak) is a sudden
      headache that is considered to be a warning symptom of impending aneurysmal
      rupture. In the presence of sudden severe headache with or without meningeal
      signs or nausea, subarachnoid hemorrhage should always be considered. Recognition
      of these warning headaches probably offers the best opportunity of reducing the
      otherwise serious mortality and morbidity of aneurysmal subarachnoid hemorrhage.
      This report describes 7 non-consecutive patients presenting warning headaches
      before major aneurysm rupture. Based on our experience and a review of the
      literature, we recommend a management algorithm for patients presenting with
      sudden severe headache.

PMID- 9198892
TI  - [Epidemiology of osteoporosis].
AB  - Osteoporosis is a systemic disease of the skeleton characterized by decreased
      bone mass and a disturbed microarchitecture of the bone. Its consequences is an
      increase in fracture risk. In women, the risk of experiencing an osteoporotic
      fracture once in life is twice as high (30-40%) as in men. In a model using
      population-based data, it is estimated that 54% of 50-year-old women present an
      osteoporotic fracture once in their remaining life. Typical osteoporotic
      fractures involve vertebral bodies, the proximal femur and the forearm. The
      number of fractures caused by osteoporosis is steadily increasing, due to greater
      life expectancy in particular. In addition, there is a secular increase in the
      incidence of fractures. In Switzerland, the number of fractures of the hip per
      year increased from 5,500 in 1980 to 9,800 in 1990 (VESKA data). The consequences
      of these fractures for the patients and their life quality and the direct and
      indirect effects on society are generally underestimated. Mortality and morbidity
      are both increased in comparison with unfractured persons of the same age. One of
      the most serious consequences of hip fractures is the loss of functional
      independence in the elderly; 10% of patients lose their functional independence
      after such fractures, and about 10% need to be placed in homes. Fractures of the
      waist lead to hospitalization in about 70% of patients aged over 85, and in many
      patients with forearm fractures algodystrophy occurs. Hip fractures are
      responsible for about 175,000 days in hospital per year for all Switzerland.
      Applied to all fractures caused by osteoporosis, this number may be much higher.
      Lack of epidemiological data, insufficient methods of investigation and the
      symptomless and silent development of osteoporosis in its beginnings have in many
      respects led to severe underestimation of this disease in the past. The extension
      of this growing worldwide health problem has only recently become apparent in
      Switzerland, essentially because of increasing life expectancy. The frequency of
      hip fractures is well documented in Switzerland and comparable with that in the
      US. It justifies in itself the development of a strategy for prevention and
      treatment. But because osteoporosis is a systemic disease of the skeleton,
      additional Swiss data on fractures other than that of the hip, such as vertebral
      and forearm fractures, would be of great interest, especially in the sector of
      ambulatory medicine.

PMID- 9198894
TI  - [Regional differences in referral for heart transplantation].
AB  - Although cardiac transplantation is a well established means of treating end
      stage heart disease, only selected patients receive this therapy. The aim of this
      study was, therefore, to investigate the frequency of referrals for and performed
      cardiac transplantations and to assess the prognosis of patients from the
      different regions of German-speaking Switzerland. From the beginning of 1989 to
      October 1995, 401 patients, aged 49 +/- 12 years, were referred to the University
      Hospital of Zurich for evaluation of the possibility of cardiac transplantation.
      149 (37%) of them were transplanted. Transplanted patients had greater cardiac
      impairment than those who were not transplanted. There was no differences in age
      or underlying diseases. More patients from the south-eastern part of Switzerland
      were referred than from the north-eastern part. In contrast to this, the
      frequency of transplanted patients was similar to all parts of Switzerland.
      Survival rate was not related to the origin of transplanted patients (1-year
      survival 80%, 5-year survival 73%) whereas overall survival in patients who were
      not transplanted was significantly worse (1-year survival 64%, 5-year survival
      45%) and differed between the various parts of our catchment area. Patients from
      regions with a high referral rate had better survival. Patients who lived in or
      near big cities were less frequently referred and had worse survival. Also,
      survival was related to the number of follow-up controls in the specialized
      clinic for heart failure and heart transplantation. In 1989 and 1994, years in
      which more than 30 patients were transplanted at our institute, only 4 of 69
      (5.8%) died while waiting for transplantation, whereas during the other years 25
      of 132 (18.9%) died (odds ratio = 0.26; p = 0.01). Moreover, the time from
      listing to transplantation was significantly shorter in 1989 and 1994 (50 +/- 66
      vs. 95 +/- 134 days, p = 0.001). CONCLUSIONS: Patients from the different parts
      of our catchment area were not equally referred for heart transplantation. The
      better survival of non-transplanted patients from regions with a high referral
      rate suggests that the possibility of transplantation is taken into account
      earlier and more frequently. Follow-up controls of these patients in a
      specialized centre seem to be useful since these patients have a better outcome.
      Nevertheless, the recruitment of donors remains the unsolved problem.

PMID- 9198895
TI  - Lung cancer in U.S. males.

PMID- 9198896
TI  - Profile: Raymond V. Damadian. Scanning the horizon.

PMID- 9198897
TI  - Early hominid fossils from Africa.
AB  - A new species of Australopithecus, the ancestor of Homo, pushes back the origins
      of bipedalism to some four million years ago.

PMID- 9198898
TI  - [Renal transplantation in patients over 60 years of age. An increasing clinical
      reality].
AB  - The elevation of the uremic population age, the longer survival of dialysis, the
      increasing number of elderly donors, together with the safer surgical,
      anesthesiological and immunological procedures have led all over the word to an
      improvement of over 60s patients transplantation program, with very good results.
      The authors present their own experience of renal transplantation in elderly
      recipients and a review of what is reported in the literature on the question.

PMID- 9198899
TI  - [Transitional carcinoma of the ureter and urinary tuberculosis].
AB  - Tumors of the renal pelvis are rare neoplasms: their yearly incidence is 1.4
      cases per 100,000 men and 0.6 cases per 100,000 women. The annual incidence of
      renal tuberculosis is 13 cases per 100,000 persons. The likelihood of both
      diseases occurring in the same kidney is extremely remote. We report on a case of
      ureter transitional cell carcinoma developed in a patient with tuberculosis
      stenosis of the same ureter, small retracted bladder and destruction of the
      opposite kidney. Total uterectomy, augmentation ileocaecocystoplasty and
      contralateral nephrectomy were performed. Literature is briefly reviewed and is
      underlined too the paradoxical simultaneous occurrence of transitional cell
      carcinoma and active tuberculosis infection, while the use of the bacillus of
      Calmette-Guerin is being advocated in the treatment of urotelial tumors.

PMID- 9198900
TI  - [Renal angiolipoma associated with bilateral double ureter. A clinical case].
AB  - Renal angiomyolipoma is a rare renal tumor usually associated with tuberous
      sclerosis, a syndrome characterized by adenoma sebaceum, mental insufficiency and
      epilepsy. The authors present a rare case of renal angio-myolipoma associated
      with bilateral double ureter, in a young male patient not affected by tuberous
      sclerosis. Histologically, the angiomyolipoma is defined by the presence of
      smooth muscular cells, new formed vessels and fat. Clinical diagnosis requires
      the utilization of various imaging techniques, like intravenous pyelogram,
      ultrasonic scan, CT scan, and FNA (Fine Needle Aspiration). In the
      histopathologic diagnosis of angiomyolipoma the use of immunohistochemical
      techniques with different antibodies has been helpful, for the necessity to
      differentiate angiomyolipoma from other epithelial tumors, as renal cell
      carcinoma and sarcomatous neoplasms. As for as treatment is concerned, the
      indication for surgery is still maintained by two factors not affected by these
      diagnostic improvements: tumor size and presence of symptoms. Tumor size is an
      important predictive growth factor of the tumor. In the absence of symptoms a
      close follow-up with ultrasonographic scan may be indicated, keeping in mind the
      possible presence of a synchronous renal cell carcinoma. Hemorrhage can be a
      fatal complication of renal angiomyolipoma, requiring emergency surgery or
      embolization.

PMID- 9198901
TI  - [Emphysematous pyelonephritis. A clinical case successfully treated with
      percutaneous drainage].
AB  - Emphysematous pyelonephritis is an unusual and serious infection, associated with
      the formation of gas by choliphormi bacteria. The authors present a case of
      monolateral emphysematous pyelonephritis in an obese and diabetic patient, put
      under observation and treated successfully through percutaneous drainage and
      antibiotic therapy.

PMID- 9198902
TI  - [Nephrogenic metaplasia. A particular clinical and anatomopathologic entity].
AB  - Two cases of nephrogenic adenoma are presented. The authors consider nephrogenic
      metaplasia as a reaction to inflammatory agents and point out the importance of
      differential diagnosis with nephrogenic adenocarcinoma, in which a different
      surgical procedure is requested.

PMID- 9198903
TI  - Metastatic tumor of the spermatic cord from a primary silent colorectal
      adenocarcinoma.
AB  - Tumors of the spermatic cord are indeed rare and 91% are of mesenchymal origin.
      Nearly all epithelial tumors are metastases with the primary tumor located in the
      gastrointestinal tract, prostate, kidney. In 9.5% of cases, initial symptoms are
      localized to the metastatic site prior to the discovery of the primary tumor.
      When a diagnosis of epithelial malignant tumor of the spermatic cord is made an
      investigation for the primary site must be performed. We report a case of
      metastatic tumor of the right spermatic cord occurring as first clinical
      manifestation of a silent adenocarcinoma of the sigmoid colon.

PMID- 9198904
TI  - [Uroangiographic contrast media, today. Elements of interest for the urologist].
AB  - Uroangiographic contrast media, as well as magnetic resonance or ultrasound
      contrast agents, are substances which are able to artificially enhance the
      contrast between different tissues, or between normal tissue and pathological
      areas. The design of ionic and nonionic, monomeric or dimeric, iodobenzene
      derivatives is outlined with attention given to historical developments and
      breakthroughs. Relationships between physicochemical properties (osmolality,
      viscosity, molecular structure, etc.) and pharmacological profile are described.
      Nonionic compounds display favourable physicochemical characteristics: high water
      solubility, low osmolality and viscosity and good systemic tolerability. Recent
      surveys on adverse reactions to uroangiographic iodinated contrast media have
      shown that the risk of severe reactions is about six times lower with nonionic
      than ionic X-ray contrast agents. The pathogenetic mechanisms of adverse
      reactions, generally classified as either anaphylactoid or osmotoxic and
      chemotoxic, are still not well understood. It has been proposed that
      leukotrienes, prostaglandins, kinins, etc., may be involved. Nitric oxide appears
      to play a crucial role in the final common pathway by which anaphylaxis-like
      reactions occur in response to contrast agent administration. The margin of
      safety (median lethal dose/diagnostic dose) for nonionic compounds is two- to
      three-fold greater than for ionic compounds. As a look at the future, an approach
      to molecules potentially useful as "blood pool X-ray contrast agents" is based on
      iodinated dendrimeric macromolecules, in which the core is triazacyclononane and
      branches are represented by trioodobenzene derivatives.

PMID- 9198905
TI  - [The use of sucralfate in radiation oncology].
AB  - PURPOSE: Radiotherapy, a cornerstone in the management of head and neck cancer,
      pelvic cancer, and esophageal cancer is associated with a marked mucosal
      toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical
      symptoms of radiation induced mucosal damage. Because there is no known way to
      obviate radiation mucositis all efforts to prevent aggravation and accelerate
      healing of mucosal changes are of great importance. Numerous agents including
      antimicrobials, local and systemic analgesics, antiinflammatory drugs,
      antidiarrheal drugs, in combination with intensive dietetic care are used to
      relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex
      sucralfate were suggested for the prevention and treatment of mucosal reactions.
      Since sucralfate protects ulcerated epithelium by coating, liberates protective
      prostaglandins and increases the local availability of protective factors this
      drug might directly interact with the pathogenesis of mucositis. PATIENTS AND
      METHOD: The results of available studies are analysed and discussed. RESULTS: The
      results of several studies indicate that sucralfate treatment especially during
      radiotherapy for pelvic cancer leads to a significant amelioration of clinical
      symptoms and morphological changes. An application of sucralfate during
      radiotherapy of head and neck cancer reveals only limited benefits in most
      studies performed. CONCLUSION: Nevertheless sucralfate is a safe, cheap and
      active drug for the prevention and treatment of radiation mucositis especially in
      patients with pelvic irradiation.

PMID- 9198906
TI  - [Planned 3-dimensional low-volume conformal irradiation of a local prostatic
      carcinoma].
AB  - AIM: Recent data have shown a significant reduction of acute side effects by
      means of a three-dimensional planned conformal radiotherapy of carcinoma of the
      prostate compared to treatment techniques used before. Theoretically, an
      optimized field coverage of the planning target volume should result in a
      reduction of treated bladder and rectum volumes. We studied the effects of
      individualized blocks on treatment volumes, planning target volumes, irradiated
      bladder and rectum volumes on basis of three-dimensional treatment planning by
      means of beam's-eye-view technique. PATIENTS AND METHOD: We compared dose-volume
      histograms of 2 different planning models, a (fictitious) open 4-field-box
      technique and a technique with conformal blocked fields designed from the beam's
      eye-view display (prescribed dose 66 Gy, daily single fraction 2 Gy). Plans of
      115 patients with localized prostate cancer treated from January 1994 to February
      1996 were analyzed. RESULTS: Using individualized fields treatment volume
      (covered by the 90%-isodose) was reduced by 23% on the average in comparison to
      the planning model without blocks. The averaged difference of treated volume and
      planning target volume, as a grade of efficiency of conformation, was reduced by
      38% (496 cm3 303 cm3) using individualized blocks. 23% of the treated bladder
      volume and 13% of the treated rectum volume had been saved on the average.
      Nevertheless, at least 11.5% of the bladder volume and 27.6% of the contoured
      rectum volume were treated with the prescribed dose (55 Gy = 100%). CONCLUSIONS:
      The comparison of dose-volume-histogram-data showed that especially high dose
      volumes of organs at risk had been saved by means of individualized blocks
      created from the beam's-eye-view. The blocks did not affect the dose distribution
      of the planning target volume adversely. Consequently the impact of these data on
      the extent of side effects and local tumor control has to be proven.

PMID- 9198907
TI  - [Telethermographic studies on the effect of immunoglobulins (Beriglobin) on heat
      radiation behavior in radiodermatitis].
AB  - BACKGROUND: Immunoglobulines are supposed to have a soothing effect on the degree
      of dermatitides and mucositides caused by irradiation. Research so far has been
      based on empiric information or reports of case studies mostly basing on
      subjective criteria. This study reports on objective thermographic measuring of
      heat radiation of dermatitides developing in the course of radiotherapy in case
      of female patients receiving postoperative radiotherapy after breast preserving
      operation on mamma carcinoma. Idea behind this is that immunglobulines affect
      inflammations of skin induced by irradiation, then also one of theses parameters,
      in this case heat, would be subject to change. PATIENTS AND METHOD: Sixteen
      patients received 10 ml Beriglobin before first and 5 ml after 5th and 10th
      radiation (corresponds to 0 Gy, 10 Gy and 20 Gy) as intragluteal injection.
      Before starting with radiation as well as after 10 Gy respectively applied, upper
      bodies of patients were examined thermographically until final dose of 50 Gy was
      reached. Here temperature progress on upper body halves exposed to irradiation
      was compared with the untreated halves as well as with upper bodies of control
      group consisting of 20 patients who had received no immunoglobuline injections.
      RESULTS: Patients who received immunoglobuline injections showed no differences
      in their skin temperature progress in comparison with the control group (Table 1,
      Figure 1). Skin temperature at the beginning as well as temperature progress
      during treatment and temperature at the end of treatment were identical in both
      groups. Also the relative temperature increase (temperature of body half subject
      to irradiation minus temperature of the other body half) was identical in both
      therapy groups (Table 2, Figure 2). CONCLUSION: Immunoglobulines (Beriglobin) do
      not influence the course of thermal radiation due to dermatitis developing during
      a series of irradiation treatments. This results in the conclusion, that
      immunoglobulines do not have any influence in the vasodilative part of dermatitis
      and vasodilative redness respectively.

PMID- 9198908
TI  - [Oxygen pressure distribution in lymph node metastases and the changes during
      acute respiratory hypoxia].
AB  - PURPOSE: The radiosensitivity of tissues is essentially influenced by hypoxia.
      Based on the oxygen effect a new therapeutic modality has been developed to
      protect healthy tissues while hypoxic breathing during irradiation. PATIENTS AND
      METHOD: The effect of hypoxic breathing (8.1% O2) on the pO2 in metastatic lymph
      nodes was studied in 14 patients. Tissue oxygenation was assessed using a
      polarographic electrode system. RESULTS: The median pO2 was 19.6 mm Hg prior to
      hypoxic breathing with a great intra- and intertumoral variability. The relative
      frequency of pO2-values < 5 mm Hg was between 0 and 88%. During hypoxic breathing
      we registered no significant changes in the mean, the median or the pO2 values <
      5 mm Hg. CONCLUSIONS: In metastatic lymph nodes can be found chronic hypoxia with
      great inter- and intratumoral pO2 variability. The hypoxic breathing (8.1% O2)
      shows no significant modifications of the tumor oxygenation with increased pO2
      variability. This fact explains the experimental and clinical experience, that
      the hypoxic breathing (8 to 10% O2) protects the healthy tissue without changes
      in the radiosensitivity of chronic hypoxic tumor tissue.

PMID- 9198909
TI  - [The results of primary radiotherapy in vaginal carcinoma].
AB  - BACKGROUND: Cancer of the vagina is the least frequent primary malignant tumor of
      the female genital tract except carcinoma of the fallopian tube. Radiation
      therapy is the preferred treatment in most cases. PATIENTS AND METHOD: Between
      1965 and 1991, 39 patients (median age 66 years) with primary carcinoma of the
      vagina were treated with radiation therapy at our clinic. The mean observation
      period was 37 months. Classification according to the FIGO yielded a stage I in
      43%, stage II in 24%, stage III in 22% and stage IV in 11%. Histological
      differentiation resulted in 35 squamous cell carcinomas and 4 adenocarcinomas. In
      69%, the tumor was found on the posterior or lateral wall of the vagina, in 43%
      it arose from the upper third of the vagina. Standard therapy consisted of
      combined brachy- and teletherapy. Most of the brachytherapy applications were
      performed with a radium source. RESULTS: Median survival was 37 months,
      calculated according to the Kaplan-Meier method. The 5-year actuarial survival
      rate for all stages was 41% (stage 1: 62%, stage II: 44%, stage III: 25%). Sixty
      eight percent of all patients achieved a complete remission, 19% a partial
      response. Significant prognostic factors were stage of disease and histological
      grading. CONCLUSION: Our results demonstrate the value of radiation therapy for
      the treatment of primary carcinoma of the vagina. Combined treatment with both
      external beam radiation and brachytherapy should be preferred.

PMID- 9198910
TI  - [A reply to the comment by K. R. Trott in Strahlenther. Onkol. 173 (1997), 146
      147 on the article by Strnad et al.: "The regression of Yoshida sarcoma during
      normoxia and hypoxia after fractionated irradiation" in Strahlenther. Onkol. 173
      (1997), 141-145].

PMID- 9198911
TI  - [Radical lymph node excision in endometrial carcinoma: the restriction of pelvic
      irradiation to node-positive cases?].

PMID- 9198912
TI  - [The quality of life after cystectomy or conservative therapy in bladder
      carcinomas].

PMID- 9198913
TI  - [Increased radiosensitivity in demonstrated p53 mutations in oral cavity
      carcinoma cell lines].

PMID- 9198914
TI  - [The postoperative T classification (pT) of primary vocal cord carcinomas and its
      significance for clinical classification (cT)].

PMID- 9198915
TI  - [Can breast cancer be prevented by drugs?].

PMID- 9198916
TI  - [Mental retardation. Progress in the search of causes means new challenge for the
      clinician].

PMID- 9198917
TI  - [Active sick-listing--an alternative to be used more often].

PMID- 9198918
TI  - [Sick leave II for backache--municipality of Kristiansand. A one-year follow up
      with and without an outpatient program].
AB  - 186 patients from Kristiansand who had been certified as sick for more than eight
      weeks because of low back pain were recruited consecutively and studied over a
      period of one year. 91 of these patients participated for three weeks in an out
      patient programme involving physical activity and theoretical education. The
      control group (95 patients) consisted of 65 patients recruited before the
      treatment group and 30 recruited after the treatment group. The duration of
      certified sick leave was reported by the national Insurance Office of
      Kristiansand. The subjective ratings of low back pain, function and quality of
      life were stated by all subjects at the time of inclusion in the study and again
      after six and 12 months. The treatment group also stated their subjective
      assessment after the three weeks of intervention. The results show a significant
      improvement of low back pain, function and quality of life in the treatment group
      only, both following the intervention and after one year. 15% of the treatment
      group were still certified as unfit for work after one year, as against 23% of
      the one and 26% of the other control group. These differences were not, however,
      statistically significant.

PMID- 9198919
TI  - [Healthier population or stricter physicians? An analysis of reduced sick leave
      in a small community].
AB  - The study More restrictive doctors or a more healthy population?, is an analysis
      of a decrease in the absence of sickness in 1994 in a community with 5,000
      inhabitants, located in Buskerud county, Norway. A variety of methods were used
      to illustrate possible contributing factors. Among possible local causes of the
      decrease is the work at the local national Insurance Office. Every person judged
      to be at risk for long-term absence from work due to illness was followed up in a
      close cooperation with the local doctors. As a result, the doctors became more
      conscious of their work in connection with certified sick leave and adopted a
      more restrictive attitude towards absence from work because of illness. This
      study has provided information and experience of interest to the local health
      services, the public health services and the National Insurance Offices.

PMID- 9198920
TI  - [Antibiotic treatment of newborn infants. Experiences from a neonatal
      department].
AB  - We have studied all newborns admitted to our neonatal intensive care unit during
      1993 and treated with intravenous antibiotics. Patient-files were examined for
      all available data at admission, focusing on factors predisposing for infection,
      symptoms, additional diagnoses, laboratory tests, bacteriology and antibacterial
      treatment. Antibiotics were given to 126 (28%) patients, of whom 90 were
      suspected of having an infection on admission. 57 of these were discharged with
      an infection-related diagnosis. 33 patients received prophylactic antibiotics, of
      whom three later developed infection. Retrospectively, 53 patients had proven or
      very probable infection. Fourteen patients tested blood culture positive. In our
      material the incidence of septicaemia was 0.45% of all newborn. Both the
      frequency of treatment and the incidence of septicaemia are consistent with the
      findings in earlier reports. We find that our material contains an unacceptably
      high frequency of false negative blood cultures. Recently published data show
      that the incidence of positive blood cultures is proportional to the amount of
      blood extracted.

PMID- 9198922
TI  - [Surfactant treatment of acute pulmonary failure. Other indications than neonatal
      distress syndrome].
AB  - In 1959 Avery and Mead suggested internationally that respiratory failure in
      premature infants is due to lack of surfactant. Surfactant is a phospholipid
      protein complex that is synthesised and stored in alveolar type II pneumocytes in
      the lungs. The main function of surfactant is to reduce surface tension in the
      lungs and make respiratory effort easier. Since 1959 much of scientific work has
      been done in this field, and there is now increasing evidence to support the
      theory that surfactant is important for normal lung function. Therefore
      surfactant insufficiency plays a major role in acute respiratory failure of any
      etiology. In this paper we focus on other possible indications for surfactant
      replacement therapy, and describe a patient with meconium aspiration syndrome
      which was treated successfully with exogenous natural surfactant.

PMID- 9198921
TI  - [Natural surfactant in routine treatment of neonatal respiratory distress
      syndrome. Experiences from two central hospitals].
AB  - Regular use of surfactant in the treatment of respiratory distress syndrome
      started in Norwegian neonatal intensive care units in 1992. The authors present
      the results for the first 70 babies with respiratory distress syndrome who were
      treated with natural surfactant from 1991 to 1994 at two level II hospitals.
      Median time of administration dropped from eight hours after birth in 1991 to
      three hours in 1994. Treatment soon after birth leads to a greater reduction in
      oxygen requirement. 12 children died, all of them very immature after complicated
      pregnancies. The total mortality in babies with a birth weight of less than 1,500
      grams was 7%. The incidence of severe bronchopulmonary dysplasia was markedly
      reduced and the total number of days on a ventilator was reduced by 50%. Use of
      surfactant was not associated with more complications. Severe respiratory
      distress syndrome should be prevented with antenatal steroids, and treated early
      postnatally with natural surfactant.

PMID- 9198924
TI  - [Better survival in neuroblastoma?].
AB  - This study compares the five year absolute survival rates among neuroblastoma
      patients treated at the National Hospital, Oslo, during two periods of time, 1985
      90 and 1967-81. The treatment regimens differed, the main difference was more
      radical operations and more intensive chemotherapy during the period 1985-90 (n =
      27) than in 1967-81 (n = 58). The intensified treatment was accomplished without
      operative mortality and without lethal complications associated with the
      cytostatic medication. For localized neuroblastoma the survival rate rose from
      64% to 93%. The results obtained for disseminated neuroblastoma (Evans' stage IV)
      remained poor, however, with survival rates of 0% in 1967-81 and 17% in 1985-90.

PMID- 9198923
TI  - [Cytomegalovirus infection in neonates. Diagnosis and therapeutic experiences].
AB  - Approximately 0.5-1% of all newborns are born infected with cytomegalovirus
      (CMV), but of these only one out of ten show symptoms at birth, most often with
      hepatosplenomegaly, thrombocytopenia, and/or brain affection. Of the remaining
      nine, one may later develop sequelae with hearing loss and/or mental retardation.
      CMV infection may also be acquired perinatally or in the newborn period, and may
      cause pneumonia and/or sepsis, possibly also gastrointestinal symptoms like blood
      in the stool, and poor weight-gain. We have diagnosed CMV infection in ten
      neonates and infants, and describe these patients in terms of symptoms, diagnosis
      and treatment. Ganciclovir is being tested in clinical trials as a treatment for
      congenital CMV infection, and was given to two of our patients with apparently
      good results.

PMID- 9198925
TI  - [Small fiber neuropathy].
AB  - A common sign of distal small fibre neuropathy is dysesthesias, especially
      burning sensation distally in the extremities. These symptoms are often difficult
      to treat with conventional analgesics. In the course of the disease, the patient
      may become less sensitive to pain and changes in temperature, but clinical signs
      may nevertheless be minor and often difficult to detect by clinical examination.
      Dysautonomic features are also common. Selective affection of small fibres may
      occur in the form of pure small fibre neuropathy, but this may also be an early
      manifestation of general sensorimotor polyneuropathy. Common causes are diabetes
      mellitus, alcoholism, and amyloidosis. Abnormalities in small diameter fibres may
      be detected by quantitative sensory testing of temperature and pain thresholds,
      and by autonomic tests. We describe four patients with polyneuropathy with a
      predominance of small fibre involvement.

PMID- 9198926
TI  - [Hemangioma and vascular malformations. Diagnosis and treatment].
AB  - The authors discuss the dilemmas associated with diagnosis and treatment of
      haemangiomas and vascular malformations. The complexity of these conditions too
      often sends the patients wandering from one specialist to another in search of an
      optimal therapeutic approach. We have established a multidisciplinary team to
      facilitate interspecialty communication on diagnosis, natural history, and
      therapy.

PMID- 9198927
TI  - [Professional conditions and satisfaction in general practice in 1993. Practice
      profile of Norwegian primary physicians].
AB  - European study of General Practice (GP) task profiles was carried out in 30
      European countries in 1993. We analyzed the Norwegian results. 164 primary care
      physicians, 51% of a random sample, answered a questionnaire. 147 kept a diary on
      their practice for one week. Compared with results from two earlier studies
      performed 15 years ago, the proportion of female GPs had doubled to 25%, there
      were more group practices, more time was spent on vocational training and
      continuous education, and night service was less frequent than in 1978. 45% were
      specialists in general practice and 7% in community medicine. Job satisfaction
      was high, and highest for women, fee-for-service GPs on contract, and GPs who
      cooperated with other health professionals.

PMID- 9198928
TI  - [Working hours and productivity of curative services in general practice in 1993.
      Practice profile of Norwegian primary physicians].
AB  - In a survey of task profiles in General Practice 164 general practitioners (GPs)
      in Norway, 51% of a random sample, answered a questionnaire and 147 doctors also
      kept a diary on their practice for one week, specifying their activities
      throughout the day. Men reported working more hours per week than women, and
      practitioners working on a fee-for-service basis had more consultations than
      colleagues on a fixed salary. Fixed salary GPs spent more time on emergency
      service. More women than men had part time jobs. The number of GPs has doubled
      from 1978 to 1993, but the total workload for a GP is approximately the same. The
      population must have doubled its consumption of primary health care services over
      this 15 year period.

PMID- 9198929
TI  - [Is there a basis for prevention of breast cancer with drugs?].
AB  - The anti-oestrogen drug tamoxifen has led to one of the most important
      improvements in therapy for breast cancer patients achieved during the last
      decades. Tamoxifen reduces risk of relapse and improves survival in women with
      breast cancer. In addition, tamoxifen has favourable effects on the lipoprotein
      metabolism, reduces morbidity and death from myocardial infarction, and
      stabilizes bone density in women after menopause. Owing to the good therapeutic
      results in breast cancer patients and the additional favourable effects of
      tamoxifen, studies were started among healthy women with elevated risk of breast
      cancer. The intention was to examine whether tamoxifen could reduce the risk of
      breast cancer development in healthy women. Recent studies, however, have
      demonstrated higher risk of endometrium cancer in breast cancer patients treated
      with tamoxifen, and higher risk of histological abnormalities in the endometrium
      in healthy women. Prevention trials, when tamoxifen is given to healthy women,
      are disputed, owing to the apparent carcinogenic effect of tamoxifen.

PMID- 9198930
TI  - [Can anything good come out of the DRG system? A tool for analyses in health
      economics?].

PMID- 9198931
TI  - [Primary health service, for good and bad].

PMID- 9198932
TI  - [Surgical treatment of ectopic pregnancy].

PMID- 9198933
TI  - [Risk prevention].

PMID- 9198934
TI  - [Short-term treatment with naproxen].

PMID- 9198935
TI  - [Reflections on pain treatment].

PMID- 9198936
TI  - [Defensive medical research].

PMID- 9198937
TI  - [Telemedicine--cost and benefit].

PMID- 9198938
TI  - [The gamma knife (radiation knife)--a progress in the treatment of cerebral
      metastases].

PMID- 9198939
TI  - [Obstructive lung disease in hospital].

PMID- 9198940
TI  - [Obstructive lung disease in a department of pulmonary medicine during the period
      1979-80].
AB  - Trends in the hospital care of patients with obstructive lung disease at the
      Department of Respiratory Medicine, Vest-Agder Central Hospital are surveyed for
      the period 1970 to end of 1988. Information was obtained from annals,
      computerised lists and patient records. The number of beds was reduced from 56-58
      during the 1970s to 29 in 1988. The stay in hospital averaged 20 days in 1970 and
      was down to five days for asthmatics and some ten days for the rest in 1988.
      Parallel to these changes these were more re-admissions during the 1980s. For a
      minority of 17 patients admitted to the department in 1988 the number of
      admissions in the course of the year totalled 165. Mean age increased from 50
      years for both sexes in 1970 to 60 years for women and 65 years for men in 1988.
      Start of symptoms before 20 years of age occurred in less than 20% of the
      patients, and the frequency of allergics was far below the figures often stated
      for the whole population. There was a marked discrepancy between the diagnostic
      labels used by general practitioners and the ones used by general practitioners
      tendency for general practitioners to label patients as asthmatics more often
      than the hospital doctors did.

PMID- 9198941
TI  - [Cerebral metastases treated with stereotaxic gamma radiation. 6-year experience
      with the "gamma knife" at the Haukeland hospital].
AB  - During the last 6 years we have treated 32 patients with 45 metastases to the
      brain in the Gamma Knife unit. 21 of these were treated exclusively with the
      Gamma Knife. The remaining 11 patients received radiosurgery for recurrent
      disease after surgery and whole-brain irradiation (six patients), new metastases
      after whole-brain irradiation alone (three patients) or for local regrowth after
      surgery (two patients). The range of tumour volume was 0.1-43.3 cm3 (median 2.4
      cm3). Marginal tumour dose was 5-30 Gy (median and mean: 25 Gy) to the 30-70%
      isodose-volume line according to tumour volume and localization. 19 patients died
      during the period of follow-up. Only three patients died from their intracranial
      metastases. Thus, local growth control was achieved in 29 patients. 16 patients
      died from extracranial manifestations. The average survival time for the patients
      who died during the observation period was 11 (1-37 months), and the survival
      time for patients still alive was 10-75 (median 14, average 29) months. Mean
      observation period for all patients was 17 (1-75) months. Brain metastases are
      physically and biologically ideal lesions to treat with radiosurgery.
      Stereotactic radiosurgery applied to radiographically small and distinct
      metastases is safe, non-invasive and highly effective. The treatment requires
      only a short stay in hospital, and is much less inconvenient to the patient than
      open surgery or whole-brain irradiation. Radiosurgery can be used on lesions
      inaccessible to open neurosurgery or resistant to classical fractionated
      radiotherapy. Gamma Knife treatment has become our first choice for patients with
      less than four intracranial metastases with diameters less than 3-3.5 cm.

PMID- 9198942
TI  - [Anisomelia. Clinical consequences and treatment].
AB  - The hypothesis that a causal relationship exists between unequal leg length and
      disorders in the back or lower extremities has been hard to prove. However, at
      the present time there is scientific documentation of an association between a
      difference in length of more than 1 cm and low back pain. Thus, in children with
      one leg one centimetre or more longer than the other, and in adults with
      symptoms, the discrepancy should be adjusted, especially if a lumbar scoliosis in
      the standing position has been documented radiographically. A difference in
      length of less than 2 cm should be treated by raising the shoe. An established or
      estimated difference of more than this is usually corrected by surgery, either by
      epiphysiodesis or by shortening or lengthening osteotomy. In adults with a
      moderate difference in leg length, a raised shoe test is recommended in order to
      evaluate the effect of a correction in practice before osteotomy is performed.

PMID- 9198943
TI  - [Abnormality as differential diagnosis in atlas fracture].
AB  - In some patients, suspected fractures of the cranial part of the cervical spine
      are difficult to diagnose properly without the use of computed tomography or MT.
      In addition to imaging and positioning problems, the possibility of anomalies of
      the atlas vertebra may complicate the diagnostic considerations. Proper knowledge
      of such anomalies may facilitate the diagnostic procedures. The diagnostic
      problems are discussed, and are illustrated through two patients recently
      examined in our department.

PMID- 9198944
TI  - [Self-reported chronic muscle pain among women in Oslo].
AB  - The prevalence and epidemiological features of chronic muscle pain were
      investigated in a cross-sectional postal survey of 2,664 females aged 25-55
      years, out of a random sample of 4,000 females in Oslo, Norway. The three-month
      prevalence of chronic widespread musculoskeletal pain was 22%, while 25% reported
      chronic localised pain. Chronic widespread pain was significantly associated with
      a number of sociodemographic factors, whereas no such associations were found for
      localised pain. Other health complaints, insomnia and low satisfaction with life,
      were more common among women with widespread pain than among women with localised
      pain.

PMID- 9198945
TI  - [Does teleradiography in primary health care reduce costs? An analysis based on
      utilization of radiographic examination in the municipality of Alta].
AB  - In a remote community in Norway all patients who had radiological examination in
      1993 were identified. Based on data from a sample of these patients, the costs to
      society of three options were calculated: i) the existing system: simple fracture
      diagnostics at the remote site, all other examinations at the nearest hospital;
      ii) teleradiology: most examinations at the remote site; iii) all examinations at
      the nearest hospital. Excluding costs common to the three options, the estimated
      annual cost was NOK 915,000 for the existing system, NOK 1235,000 for the
      teleradiology option and NOK 1170,000 for the "all-at-hospital"-option.
      Teleradiology services to remote primary health care do not appear to save costs.
      However, teleradiology may be justified on the grounds that it increases equity
      of access to care as well as the quality of health care in remote communities.

PMID- 9198946
TI  - [Bad breath from the oral cavity].
AB  - Halitosis, or bad breath, is a clinical problem for many people. In the majority
      of cases the problem has been shown to originate in the oral cavity. All
      conditions that favour the retention of anaerobic, mainly gram-negative, bacteria
      will predispose for the development of bad breath. In addition to periodontal
      pockets, the most important retention site is the dorsum of the tongue with its
      numerous papillae. The bacteria metabolize sulphur-containing amino acids to
      yield the volatile sulphur-containing compounds hydrogen sulphide and
      methylmercaptane. These substances have an offensive odour in very low
      concentrations. The sulphur compounds may also damage the surrounding tissue
      directly, and thereby contribute to the initiation and development of periodontal
      disease. During the night and between meals the conditions are optimal for odour
      production. The importance of regular meals is therefore emphasized. To
      supplement conventional oral hygienic measures the patients are advised to brush
      their tongue. The use of oral care products which contain metal ions, especially
      zinc, will inhibit odour formation because of the affinity of the metal ion to
      sulphur. It is also possible to measure the level of volatile sulphur-containing
      compounds in the air in the mouth directly by means of a portable sulphide
      monitor. Dentists and physicians are both advised to discuss the problem of
      halitosis with their patients, since this should be regarded as an important
      aspect of the patient's health.

PMID- 9198947
TI  - [Quality assurance in rheumatology. Evaluation of a team work model between
      general practitioners and a rheumatologist].
AB  - The intention of the project was to heighten the theoretical and practical skills
      of general practitioners in the care of patients with musceloskeletal problems.
      Six general practitioners and a rheumatologist participated. The rheumatologist
      joined the general practitioners at two health centres, which he visited on two
      occasions with an interval of six months. The patient and case history were
      presented by the local physician, and an additional historical and physical
      examination was performed by the rheumatologist. The physicians were trained in
      relevant examination techniques. The study was evaluated by means of
      questionnaires to the doctors and interviews with six patients. The theoretical
      knowledge of the general practitioners increased by an average of 23%. Both
      general practitioner and rheumatologist observed improvement in examination
      techniques. This parameter was not specifically evaluated. The patients
      appreciated the way in which they were treated. They found that the first and
      second line health care served as a smooth-working team. The cost of this project
      was low. The model is being continued at the request of the general
      practitioners.

PMID- 9198948
TI  - [Vasculitis and malignant diseases].
AB  - Approximately 1 - 7% of all patients with cutaneous vasculitis have an associated
      malignant disease. In such cases, vasculitis most often accompanies myelo- and
      lymphoproliferative diseases. Histologically, leukocytoclastic or panarteritis
      nodosa-like vasculitis are the most frequently observed types, and in most
      instances manifest clinically as palpable purpura. Malignancy should be suspected
      if the clinical picture does not fit into any well defined category of connective
      tissue disease, and when drugs and infection are excluded as causes of the
      vasculitis. The author discusses possible mechanisms of paramalignant vasculitis.

PMID- 9198949
TI  - [Increased concentration on research of women's health].

PMID- 9198950
TI  - [Crisis of academic medicine].

PMID- 9198951
TI  - [University medicine in Silicon Valley].

PMID- 9198953
TI  - [Death diagnosis and hypothermia].

PMID- 9198952
TI  - [Postpoliomyelitis syndrome].

PMID- 9198954
TI  - [Where does geriatric care go?].

PMID- 9198956
TI  - [Archiving of radiologic pictures].

PMID- 9198955
TI  - [Clearing after erroneously administered racemic adrenaline].

PMID- 9198957
TI  - [Culture and health].

PMID- 9198958
TI  - [Taxonomy of European and Persian fallow deer on the basis of bone remains in
      Turkey].
AB  - The site of Sirkeli Hoyuk is located on the Cukurova-Plain in southern Turkey
      upon the river Ceyhan. During the excavation bones were recovered from strata
      that date from the Chalkolithikum (4th millenium B.C.) to Hellenistic-Roman Times
      (2nd/1st century B.C.). The analysis of these remains evaluates the nutritional
      habits of the Hoyuk inhabitants and the reconstruction of the former landscape.
      Apparently it consisted of a vast steppe with gallery forests along the rivers
      and fens. The identification of the deer bones posed considerable problems,
      because the site is located in the region, where the distribution areas of
      European and Persian Fallow Deer overlap. Up to now these cervides were usually
      regarded as two different species. Antler morphology as well as size variation in
      the bones of prehistoric Fallow Deer suggest a closer relationship between the
      two forms, for which a subspecific status is proposed.

PMID- 9198959
TI  - [Case report. House-cat, castrated male, sixteen-and-a-half years old].

PMID- 9198960
TI  - [Federal investigations on the distribution and in vitro resistance of udder
      pathogenic bacteria in the milk of cows with subclinical mastitis].
AB  - 1644 quarter milk samples of 948 dairy cows with subclinical mastitis, collected
      from 63 veterinary practices all over Germany origined by 262 livestocks with
      problems in udder health were examined semiquantitatively by "Aulendorfer
      Mastitistest" for cell count and additionally bacteriologically. Potentially
      udder pathogenic bacteria were tested for in vitro-sensitivity to penicillin G,
      ampicillin, oxacillin, cefacetril, tylosin, neomycin, gentamicin, polymyxin B and
      enrofloxacin. 24.5% of all tested milk samples were bacteriologically negative.
      In 35.3% of the bacteriological positive milk samples Staphylococcus (S) aureus
      was detected. Enterococci, Streptococcus (Sc.) uberis, Sc. dysgalactiae and Sc.
      agalactiae were found in 8.9%, 8.2%, 8.1% and 4.9% of all positive milk samples,
      respectively. G-streptococci were found only occasionally. Apathogenic bacteria
      like coagulase-negative staphylococci, micrococci, aerobic bacilli and
      coryneforms were detected in 45.0% of all positive milk samples.
      Enterobacteriaceae (E. coli, klebsiella spp., proteus spp. and other coliforms)
      were isolated in 3.3% of all cases and should be considered as insignificant for
      the subclinical mastitis of dairy cows in Germany. Against S. aureus cefacetril
      and oxacillin were mostly effective in vitro, whereas penicillin G was
      ineffective because 40% of these bacteria are penicillinase-positive.
      Streptococci and enterococci were mostly sensitive to cefacetril, oxacillin,
      penicillin G and ampicillin. Concerning the distribution of bacteria regional
      differences were recognized. Regional differences concerning in vitro-sensitivity
      were negligible. The results are discussed.

PMID- 9198961
TI  - [Sucking and drinking behavior as criteria of vitality in newborn calves].
AB  - Newborn dairy calves (n = 82) were investigated for relations between frequency
      and intensity of sucking movements at the one hand and course of parturition,
      values of a modified Apgar-Score, time between birth and first standing as well
      as parameters in the blood (lactate, glucose, immunoglobulins, pH, base excess,
      pCO2) and the incidence of newborn diseases at the other hand. In another group
      101 dairy and 533 crossbred calves (dairy x beef) were compared with regard to
      the course of parturition, vitality, sucking behaviour and the ability to stand
      and drink without help 12 hours post natum. Sucking behaviour can be recommended
      as a criterion of vitality alone or as part of a modified Apgar-Score. A
      frequency of 80 and more intensive sucking movements/min sucking time and the
      ability to stand and drink without human help within 12 hours post natum are
      physiological. In milk x beef crossbred calves this ability can be impaired even
      in cases of normal birth.

PMID- 9198962
TI  - [Purulent inflammation of the fetlock joint in cattle--treatment by joint
      resection].
AB  - A surgical method for the treatment of purulent inflammation of the fetlock joint
      in cattle is reported. The method involves opening of the diseased joint and
      complete removal of diseased tissues (articular resection). Three of four cattle
      with purulent inflammation of the fetlock joint could be successfully treated
      using this procedure. Following complete removal of the fetlock joint
      ossification took place. The use of the limb was little affected in all gait
      types following the ossification of the fetlock joint. One cow was not healed,
      since it was not possible to resect the affected tissues completely.

PMID- 9198963
TI  - [Parasitic infections and herd fertility. An overview].
AB  - The negative impact of a parasitic infection not only affects the weight gain of
      the replacement heifer, but also her reproductive performance and hence the
      productivity of a cow-calf herd. A parasitic infection in the period between
      weaning and first service can put at risk the continuous weight gain essential
      for early reproductive maturity at 14-15 months. If, as a herd measurement, the
      so-called "critical minimum bodyweight" is not achieved by the timing set in the
      insemination or service plan, negative economic effects result, in the form of
      prolonged service periods and longer calving patterns. An effective parasite
      control plan in this critical time frame results in securing a high level of
      fertility. Such a parasite control programme should be carried out as a strategic
      measure, taking into account the age of the animal (susceptibility) and the
      natural risk of infection (pasture contamination). The treatment at the end of
      the grazing period at the time of housing is of particular importance.

PMID- 9198964
TI  - [Predictive value of back fat thickness for body fat content in cattle].
AB  - Back fat thickness was measured at six points in 251 beef heifers aged 3 to 17
      months, in 27 beef bulls aged 15 months and in 200 SMR-cows of different age.
      This was paralleled by estimation of body composition based on total body water
      analysis. All groups of animals showed the same pattern of back fat thickness for
      the measuring points investigated. This lead to the result of one optimum
      measuring point for determination of back fat thickness, which will be described.
      The portion of body fat relative to body weight change showed great variations in
      dependence on age. Therefore live weight is of limited relevance for the
      estimation of body condition. The correlation coefficients between back fat
      thickness and body fat content were estimated to be between 0.80 and 0.87 for all
      groups investigated. Change in back fat thickness by 1 mm corresponded to gain or
      loss of around 5 kg body fat in all animal groups. Hence, measurement of back fat
      thickness is a suitable method for objective estimation of body condition.

PMID- 9198965
TI  - [Breeding hygiene regimen and fertility performance in a swine herd of 400].
AB  - A specific breeding schedule and the subsequent reproductive performance in a 400
      swine breeding herd over five years is described. The reduction of the nursing
      time from 49 to 28 days increased the number of litters per anno to 2.4 and of
      weaned piglets by six. The reproductive management is based on the 7-day-breeding
      schedule. Each week 22 to 23 animals are inseminated, among them eight gilts
      every 14 days. Mating gilts only every 14 days reduce the cost for
      transportation. The zoo- and biotechnique is as follows: Sows: weaning on
      Wednesday; 24 h later 900 IE pregnant mare serum gonadotropin (PMSG) i.m.,
      artificial insemination (AI) on Monday or Tuesday (two times), pregnancy
      diagnosis by transcutaneous ultrasonography on day 23/24 post insemination.
      Gilts: transportation (gilts are bought-in) exactly four weeks before
      insemination; on Saturday/ Sunday transportation induced heat; 23 days after
      transportation (18th/19th day of female cycle), on Friday 900 IE PMSG (with sows
      simultaneously); on Monday 150 micrograms GnRH-analogue i.m.; on
      Wednesday/Thursday AI (two times; the 2nd AI 14 h after the first), pregnancy
      diagnosis by transcutaneous ultrasonography on day 23/24 post insemination.

PMID- 9198966
TI  - [Appearance of antibodies against Borrelia burgdorferi in different populations
      of pigeons (Columba livia var. domestica vel urbana].
AB  - Borrelia burgdorferi, the causative agent of Lyme borreliosis, can infect both
      mammals and birds. The purpose of the present survey was to determine the
      presence of antibodies against B. burgdorferi in different populations of
      pigeons. 1043 sera from pigeons (carrier-, urban-, show-pigeons) were examined by
      standard serological methods. B.burgdorferi shows crossreaction with B. anserina.
      Therefore all sera were evaluated by IFAT and ELISA for both Borrelia species.
      The results demonstrate no evidence for the pigeons (Columba livia var. domestica
      vel urbana) to be reservoir for Borrelia burgdorferi.

PMID- 9198967
TI  - [Anatomy of the fetlock joint in horses by means of joint casts].
AB  - The equine fetlock joint cavity shows ten pouches. The dorsal recess, which is
      oriented to the proximal side, is separated from those three pouches, which show
      to the distal direction, by several capsular folds. These folds are documented by
      means of sagittal sections through the fetlock joint. A medial/lateral recess is
      covered by the deep part of the collateral ligament of the fetlock joint. The
      collateral ligaments as well as the sesamoidean collateral ligaments are closely
      connected with the joint capsule, from which two capsular folds are separated.
      Between the part of the sesamoidean collateral ligament, that inserts to the
      metacarpus/metatarsus and the part that inserts to the proximal phalanx, the
      fetlock joint cavity pouches as Recessus palmaris/plantaris distalis
      medialis/lateralis. The palmar/plantar distal pouch, which lies in the median
      line, is covered by the Ligamentum sesamoideum rectum. This recess is narrowed
      down by the cruciated sesamoidean ligaments. The dominant palmar/plantar proximal
      recess is subdivided into several small pouches by strings or bands of the joint
      capsule, which can already be seen with an unaided eye.

PMID- 9198968
TI  - [Minimal-flow anesthesia in the dog].
AB  - Many veterinary practices possess an anesthetic machine with a rebreathing
      system, and therefore the facility to induce anesthesia under more cost-effective
      reduced fresh gas flow conditions in a semi-closed system. However, as the fresh
      gas flow is frequently far too high, the rebreathing element is used rarely or
      not at all, making the anesthesia unnecessarily expensive. The relationships
      between the fresh gas setting and the final concentrations of expired air are
      discussed, and experience in 53 dogs with minimal flow anesthesia (500 ml/min),
      an extreme variant of anesthesia induction using a semi-closed system with
      minimal excess gas volume and a high proportion of rebreathed gas, is described.

PMID- 9198969
TI  - [Intascleral silicone prosthesis in the dog: a retrospective study of 22 cases].
AB  - Over a period of five years 28 dog eyes were treated by evisceration and
      implantation of an intrascleral silicone prosthesis. During an average follow-up
      period of 2.93 years the only complication noted was a mild entropion in one
      case. The majority of dog owners were satisfied with the cosmetic result. All of
      them would again opt for this procedure and prefer it to an enucleation. The
      postoperative management was well tolerated by both animals and owners. After
      careful preoperative work-up and ruling-out of intraocular neoplasms,
      evisceration/prosthesis is a simple and practical method to salvage buphthalmic
      eyes and globes with beginning phthisis bulbi. Intraocular tumors and septic
      endophthalmitis are the two principal contraindications. In addition, eyes with
      deep or even perforated corneal ulcers should not be fitted with an intrascleral
      prosthesis.

PMID- 9198970
TI  - [Canine hypothyroidism: detection of anti-thyroglobulin autoantibodies].
AB  - An enzyme-linked immunosorbent assay was established to detect autoantibodies in
      canine patients with hypothyroidism. Thyroglobulin, purified from thyroid glands
      of euthanized, healthy dogs, was used as antigen. Utilizing this test system,
      sera of 39 patients with hypothyroidism were screened for the presence of
      thyroglobulin specific autoantibodies. Positive titers were found in 38% of these
      dogs, whereas 18 out of 72 patients (25%) with other internal diseases showed a
      positive reaction. In addition 21 healthy dogs were tested for the presence of
      anti-thyroglobulin autoantibodies. Three dogs were found to be positive in the
      ELISA. Development of autoantibody titers was followed up in four cases over a
      period of one year. A steady decline of autoantibody titers was observed in three
      patients with hypothyroidism, whereas titers of one healthy dog remained high
      over this period.

PMID- 9198971
TI  - [Examination of commercial hedgehog feed for its quality (acceptance,
      digestibility, and nutritional composition)].
AB  - Six commercial hedgehog feedstuffs were evaluated (palatability, composition and
      digestibility of crude nutrients and minerals). 14 healthy adult hedgehogs were
      fed these products and one self mixed diet based on minced beef and egg. The
      composition of all commercial diets was very similar. The components used mostly
      were cereal products but also animals like insects and prawns were seen. Gross
      energy was between 1.9 and 2.3 MJ/100 g DM. The concentrations of the minerals
      were partly very low (Ca, P) and in some products the relation between Ca and P
      was unsuitable. Even with individual differences between the animals the
      palatability of the self mixed diet was generally higher. Contrary to the self
      mixed diet the digestibility of crude protein of the commercial feed was moderate
      (93 vs. 73-77%). Crude fat was highly digestible (80-92%). In spite of a low
      activity of amylase in pancreas and chyme the digestibility of the nitrogen free
      extracts was very high (67-86%), probably due to thermal processing of the
      cereals. Since crude fibre has a negative effect on total digestibility (r = 
      0.78) its concentration should be under 3% in the whole diet. The average net
      absorption rates of minerals were: Ca: +/-0%; P: 50%; Mg: 24%; K: 85% and Na:
      80%. Based on this knowledge first recommendations for the composition of
      nutritionally balanced complete feeds are given.

PMID- 9198972
TI  - [Short evaluation of the QBC-Vet Autoread System].
AB  - The QBC-Vet Autoread-System (QBC = Quantitative Buffy Coat) is an advanced
      version of the OBC-Vet Haematology-System, to which an automatic reader and a
      printer have been added. In addition to the determination of haematocrit,
      haemoglobin, MCHC, white blood cell, granulocyte, lympho-/monocyte and platelet
      counts, measurement of eosinophils and neutrophils in dogs, and the estimation of
      reticulocytes and nucleated red blood cells in both dogs and cats are possible.
      The aim of this study was to evaluate the QBC-Vet Autoread-System with respect to
      its suitability in veterinary practice. Samples collected from 213 mostly ill
      animals were analysed and the results compared with conventionally measured
      values. The system was found to be easy both in handling and interpretation of
      results. Accuracy was found to be good for the majority of the parameters
      (correlation coefficients: haematocrit r > 0.96, WBC r > 0.89). The printed buffy
      coat profile was found to be very useful to verify accuracy of results
      immediately and to prevent misinterpretations. Although this is a preliminary
      study with a small number of samples, the QBC-Vet Autoread-System was found to be
      a true improvement over the older system and will be very useful in veterinary
      practices.

PMID- 9198973
TI  - [Cat-scratch disease: historical, clinical, phylogenetic and taxonomic aspects].
AB  - The cat-scratch disease (CSD) is known as a nosological entity since 1950. It was
      diagnosed by the clinical symptoms, epidemiologic data, and the intracutaneous
      test of Hanger and Rose. The aetiologic agent is Bartonella (formerly
      Rochalimaea) henselae occurring in thirty to fifty percent of healthy cats. The
      gramnegative alpha-2-proteobacteria cause the CSD but also fever in healthy
      humans. Patients suffering from AIDS show bacillary angiomatosis, bacillary
      peliosis hepatis, endocarditis, and septicemia. There is an open question for
      other aetiologic agents causing CSD as cofactors. For example, Afipia felis is
      found to a certain extent from patients suffering from CSD. Furthermore, Rothia
      dentocariosa was isolated in lymphnodes of CSD patients, and also other
      grampositive rods may play an important role together with B. henselae in CSD.

PMID- 9198974
TI  - [The characteristics of the postmortem dynamics of human body temperature].

PMID- 9198975
TI  - [An expert study of the action of an explosion on the human body].

PMID- 9198976
TI  - [A hemin study of hemorrhages in the area of stab-cutting wounds].

PMID- 9198977
TI  - [Experience in using hair as the object of study in forensic medical molecular
      genetic expertise].
AB  - It is possible to overcome the difficulties in expert evaluation of hairs by
      using molecular genetic methods of analysis at the level of DNA. We assessed the
      possibility of using hair for forensic genetic identification of relation and
      personality identification. The efficacy of using just individual hairs in
      analysis has been demonstrated. The stability of results was evaluated and the
      possible artefacts caused by low content of DNA and its possible degradation
      detected and corrected.

PMID- 9198979
TI  - [The 4th All-Russian Congress of Forensic Physicians].

PMID- 9198978
TI  - [The diagnosis of human sex and body height from fragmented bone remains
      (Methodological Recommendations No. 94/267 approved by the Ministry of Health and
      the Medical Industry of Russia 3 July 95)].

PMID- 9198980
TI  - [The complex detection of AB(O)-system antigens and of keratin polymorphism in
      the forensic medical study of hair].
AB  - Hair proteins were extracted by buffer consisting of 8 M urea, 0.025 M
      dithiothreitol, 2% sodium dodecylsulfate, and 0.01 M tris-HCl pH 10.4. The
      proteins were analyzed by gradient polyacrylamide gel electrophoresis. A single 5
      cm hair, previously subjected to AB0 blood group analysis by the absorption
      elution test, was sufficient for assessing the keratin phenotype. It is possible
      to determine the AB(0) antigens and detect the keratin phenotype in the same hair
      fragments.

PMID- 9198981
TI  - [The detection of the Glm(1) antigen by the indirect immunofluorescence reaction
      in a quantitative modification].
AB  - Quantitative modification of indirect immunofluorescence test permits the
      detection of Glm(1) antigen in spots on material evidence in much lower
      concentrations than are detectable by the routine method. Use of the Stat
      software helps objectively assess the test results after mathematical processing
      thereof and reliably judge about the presence of the Glm(1) antigen in the tested
      material.

PMID- 9198982
TI  - [The assessment of the degree of severity of isolated and combined injuries to
      the nose].

PMID- 9198983
TI  - [The characteristics of extracting 4-methyl-2,6-dinitrophenol and 2-(1
      methylpropyl)-4,6-dinitrophenol from aqueous solutions].

PMID- 9198984
TI  - [The coordination of the forensic medical service with the medical criminology
      subdivisions of internal affairs organs in the personal identification of
      unidentified corpses].
AB  - In order to improve the cooperation between medical criminology departments of
      the organs of home affairs and forensic medical service in personality
      identification of unidentified corpses, the authors propose amendments to the
      routine procedure regulated by documents of the Ministry of Home Affairs of the
      Russian Federation, for these documents are in need of serious correction and
      revision, so that they conform to the judicial legislation and other documents.

PMID- 9198986
TI  - [Experience in the organization of joint research work with research institutes
      and practical departments].

PMID- 9198985
TI  - [The coordination of the forensic medical service with the obligatory medical
      insurance funds].

PMID- 9198987
TI  - [The verification of the conclusions of an expert (expertise on corpses)].

PMID- 9198988
TI  - [The use of the complexometric indicator glycine cresol red as a stain in
      neurohistology].

PMID- 9198989
TI  - [The procedural characteristics in identifying the parts of a dismembered human
      corpse and meat products].

PMID- 9198990
TI  - [Isolated trauma of the pancreas and splenic artery].
AB  - Isolated ruptures of the pancreas and splenic artery resulted from a strike to
      the abdomen with a blunt instrument. The patient (aged 36 years) died in 24 h
      from slow bleeding from the ruptured splenic artery into the omental sac cavity
      closed with adhesions.

PMID- 9198991
TI  - [The establishment of the cause of death from bites by animal teeth under unknown
      circumstances of the trauma].

PMID- 9198992
TI  - [The completion of the work on collecting and classifying the Russian literature
      on forensic medicine].

PMID- 9198993
TI  - [Problems with the order of admittance to the performance of the professional
      activities of forensic medical experts].

PMID- 9198994
TI  - [The mechanism of the formation and the morphological characteristics of intra
      brain stem hemorrhages in craniocerebral trauma].

PMID- 9198995
TI  - [Sports medicine service in Denmark].

PMID- 9198997
TI  - [A dermatologist on the Internet].

PMID- 9198996
TI  - [Hip fractures].

PMID- 9198998
TI  - [Latex allergy].
AB  - Latex allergy has been described with increasing frequency throughout the last
      years. The prevalence in Denmark is not yet known. The growing frequency is
      partly explained by the extensive use of latex-containing products (especially
      gloves), which has followed the appearance of the HIV-epidemic. The symptoms of
      latex allergy are usually those produced by type-I hypersensitivity. Type-IV
      allergy (contact dermatitis) to rubber chemicals is well described but is not
      directly associated with the latex proteins. The allergens in latex have nearly
      been identified; diagnostic tools are known but are not yet satisfactory. Cross
      reacting antigens are found in banana, kiwi, avocado, chestnut and other plants.
      It is concluded, that attention to latex allergy has to be intensified and the
      risk factors reduced, especially concerning the health care units.

PMID- 9198999
TI  - [Treatment of colorectal cancer with monoclonal antibodies].
AB  - This article reviews the treatment of colorectal carcinoma with monoclonal
      antibodies. Since the late seventies, several hundred patients with advanced
      disease have been treated with unconjugated antibodies, especially Mab 17-1A. The
      response rate of the studies has been less than 10%. In contrast, Mab given as
      adjuvant treatment for Duke's C colorectal carcinoma increased the five year
      survival with 30%. The actions of different types of immunoconjugates are
      reviewed.

PMID- 9199000
TI  - [Continuing medical education via questionnaire studies. Three pilot projects for
      anesthesiology, cardiology and neurology].
AB  - The Danish Medical Association and the scientific societies have initiated three
      studies to evaluate the use of questionnaires for continuous medical education.
      One study was a questionnaire in anaesthesiology with 30 questions with answers
      yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study
      was in cardiology with a multiple choice questionnaire, sent to 300 general
      practitioners and 75 specialists in internal medicine outside cardiology. One
      study concerned the educational value of State-of-the-Art articles about
      neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association)
      sent to 500 doctors outside neurology. All questionnaires were sent anonymously,
      with one general reminder. For the anaesthesiology study 234 questionnaires were
      returned (40.5%). In the cardiology study 195 questionnaires were returned (52%).
      For the study on neurology 278 answered (56%). Only about half of the
      questionnaires were returned for the three studies, and a lot of effort and
      resources were put into the studies. An extension from these small pilot studies
      to a general systematic continuous methodology with updated questionnaires in the
      postgraduate medical education seems troublesome. An optional self-registration
      for medical education such as The Canadian "Mocomp concept" might be a more
      realistic suggestion.

PMID- 9199001
TI  - [Injury pattern in a sports club with its own sports physician].
AB  - As the first Danish athletic association, TST-79 in 1995 appointed a permanent
      sports doctor for use by all its members. We publish the results of the first
      year. Seventeen percent of all handball players and 11% of all football players
      were seen in the consultation. The athletes were between 10 and 69 years old.
      Seventy-eight percent of the injured athletes could be diagnosed, instructed and,
      if necessary, treated after one consultation. Eight percent were sent for further
      examination at a hospital. Ultrasound examinations were necessary for
      establishing the diagnosis in 10% of the injured athletes. Some of the injuries
      were serious, and would probably not have been seen if the athletes did not have
      the possibility of consulting a sports doctor. This would increase the risk of
      chronic injury. It is suggested that a permanent arrangement with a sports doctor
      is an economically reasonable investment.

PMID- 9199003
TI  - [Thymomoa in Denmark].
AB  - This is a descriptive study of thymomas notified to the national Danish Cancer
      Registry and registered by the departments of pathology during the years 1943
      1993. A total of 433 cases of benign and malignant thymomas were included over
      these 50 years with an increase of the incidence to a stable rate of
      2.5/million/year from start to 1973. The male:female ratio is 1:1. While the age
      specific incidence rate for persons below 40 years is constantly low throughout
      the period of investigation, a doubling of the rate is registered for persons
      between 70 and 79 during the period 1978-1993. The incidence rate in Copenhagen
      is much higher compared to other regions of Denmark. The above-mentioned increase
      in incidence is due mainly to an underreporting of benign thymomas during the
      first period of investigation (1943-1977), but may also be due to improved
      diagnostic capabilities and to more uniform methods of registration during the
      last period (1978-1993).

PMID- 9199002
TI  - [How valid are self-reported intakes of beer, wine and spirits in population
      studies?].
AB  - In order to compare data on intake of wine, beer and spirits from a frequency
      questionnaire with intake of each type of alcoholic beverage estimated from a
      dietary interview, a randomly selected sub-sample of 244 women and 249 men aged
      35-65 years was cross-sectionally studied. The sample was a sub-sample of the
      Danish MONICA study. Mean outcome measure in the study was the differences in
      intake of beer, wine and spirits as reported by the frequency questionnaire and
      the diet history interview. We found an overall agreement between the two
      methods, with very little or no systematic variation for all three alcoholic
      beverages. We conclude that compared to a more time and money consuming thorough
      dietary interview, the traditional frequency questionnaires seem to sufficiently
      capture intakes of different types of alcohol. Bias in alcohol reporting by the
      frequency questionnaire does not seem responsible for the recently found
      decreased mortality among subjects with a daily intake of wine, nor the increased
      mortality from drinking of spirits.

PMID- 9199004
TI  - [Prenatal and postnatal prevalence of Turner syndrome. A registry-based study].
AB  - The prevalence of Turner's syndrome in Denmark 1970-1993 was studied and the
      validity of prenatal diagnosis was assessed. The study was conducted on prenatal
      and postnatal Turner's syndrome in the Danish Cytogenetic Central Register. All
      registered Turner's syndrome karyotypes (100 prenatal cases and 215 postnatal
      cases) at the Danish Cytogenetic Central Register were included. The main outcome
      measures were prevalence of Turner's syndrome karyotypes among prenatally tested
      fetuses and Turner's syndrome among liveborn infants. The results showed that
      among infant girls, prevalence of Turner's syndrome was 32/100,000. Among female
      fetuses tested by amniocentesis, prevalence of Turner's syndrome karyotypes was
      176/100,000 (relative risk of syndrome, 6.74 compared with prevalence among
      untested pregnancies). Among female fetuses tested by chorion villus sampling,
      prevalence of syndrome karyotypes was 392/100,000 (relative risk, 16.8). We
      excluded prenatal tests referred because of results of ultrasound scanning: among
      fetuses tested by amniocentesis revised relative risk was 5.68, while revised
      relative risk among fetuses tested by chorion villus sampling was 13.3. For 29
      fetuses with prenatal diagnosis of possible Turner's syndrome, pregnancy was
      allowed to continue and 24 of the children were live born. Thirteen of the
      liveborn children were karyotyped postnatally, and the diagnosis of Turner's
      syndrome had to be revised for eight, seven being normal girls and one boy. This
      gives a tentative predictive value of amniocentesis in the diagnosis of Turner's
      syndrome between 21% and 67%. There was no significant relation between mother's
      age and risk of Turner's syndrome. In conclusion, a discrepancy between prenatal
      and postnatal prevalence of Turner's syndrome challenges the specificity of
      prenatal examination in diagnosing Turner's syndrome.

PMID- 9199006
TI  - [Latex allergy in children].
AB  - More than a thousand cases of type-1 latex allergy have been presented. In
      children the condition is most often described in patients with spina bifida. Six
      cases of latex allergy in atopic children are presented. Five of these had food
      allergies, especially to banana. The allergy was verified with prick-test, LHR
      test and measurement of specific IgE. It is concluded that attention to latex
      allergy in atopic children has to be intensified. Prick-test with standardised
      latex extracts is the preferred method for diagnosis of the allergy. Latex
      dummies, latex toys, balloons etc, have to be avoided.

PMID- 9199005
TI  - [Experience with daily single dose administration of gentamicin].
AB  - The purpose of the study was to evaluate the effect and side-effects of once
      daily (OD) administration of gentamicin. The study was a retrospective analysis
      of patients treated with gentamicin OD for at least two days for proven or
      suspected infection. Of the 101 patients included, 60 were female, and the median
      age was 64 years (range: 20-90 years). Median duration of treatment was six days
      (2-63 days). All patients received combination therapy with two (36 patients),
      three (64 patients) or four (one patient) antibiotics, apart from gentamicin
      usually ampicillin, cefuroxime and/or metronidazole. Gentamicin doses were
      usually 240 mg on a fixed basis, but reduced in patients with pre-treatment
      impairment of serum-creatinine. Bacteriological cultures were taken in 90% of the
      patients, of which 59% were positive, most often with Enterobacteriaceae (57%) or
      other Gram-negative rods (11%). Effect of antibiotic treatment was seen in 82% of
      the patients. Nephrotoxicity defined as a 44 umol/l increase in serum-creatinine
      during treatment was found in five patients (5%). Ototoxicity, i.e. clinical
      signs of tinnitus, dizziness and/or impaired hearing, was reported in two
      patients. In conclusion, gentamicin OD with 240 mg is easy to administer, appears
      to be sufficient with regard to effect and has a low frequency of side-effects.

PMID- 9199007
TI  - [Lyme neuro-borreliosis in a 66-year old women. Differential diagnosis of
      cerebral metastases and cerebral infarction].
AB  - A 66-year-old woman with medically treated hypertension and a recent operation
      for breast cancer was admitted because of burning pain localized between her
      shoulder blades and a paretic, dysaesthetic right arm. CSF examination revealed
      lymphocytic pleocytosis and specific IgM Borrelia burgdorferi antibodies. CT was
      normal. The patient was treated intravenously with high doses of penicillin for
      14 days, and within one month of admission she had recovered completely
      neurologically. During the first days of treatment a drop in blood pressure, ECG
      changes, and further neurological changes were observed, but disappeared
      spontaneously within three days. The patient did not recall a tick bite, and the
      case illustrates that neuroborreliosis may be a differential diagnosis to stroke
      or cerebral neoplasms in elderly patients.

PMID- 9199008
TI  - [Screening for life--in general practice].

PMID- 9199009
TI  - [Prevention of non-insulin-dependent diabetes mellitus].

PMID- 9199010
TI  - [Evidence-based medicine and disseminated intravascular coagulation (DIC)].

PMID- 9199011
TI  - [Diagnostic invasive examination in primary lung cancer].

PMID- 9199012
TI  - [Postoperative nausea and vomiting--an economical consideration].

PMID- 9199013
TI  - [Lightning (and electric) injuries].

PMID- 9199014
TI  - [Apoplexy].

PMID- 9199015
TI  - [Anticoagulation in cerebral ischemia?].

PMID- 9199016
TI  - [Anastomosis leakage--risk factors].

PMID- 9199017
TI  - [Do NSAIDs damage articular cartilage?].

PMID- 9199018
TI  - [EDTA chelation--a medical treatment and a surgical problem].

PMID- 9199019
TI  - [Laser treatment in dermatology].

PMID- 9199020
TI  - [Vaginal cytology in gynecology].

PMID- 9199021
TI  - [Depression].

PMID- 9199022
TI  - [A rheumatologist on the Internet].

PMID- 9199023
TI  - [Dermatological laser treatment. A review of therapeutic possibilities and
      equipment].
AB  - Laser light is monochromatic light that is delivered either in order to perform a
      precise thermal destruction of specific skin components or in order to ablate
      skin in an unspecific, but highly controlled way. Optimal dermatological laser
      treatment requires carefully selected laser wavelengths for specific indications.
      It is recommended that laser treatment of vascular lesions such as naevus
      flammeus and haemangiomas is carried out in early childhood. In laser treatment
      of benign, pigmented lesions it is important to distinguish between epidermal and
      dermal lesions, since treatment response as well as optimal laser wavelengths
      depend on this subclassification. The treatment of tattoos is undertaken by
      different laser types, of which the most optimal can be selected by skin
      reflectance measurements. Novel fields of indications for dermatological laser
      therapy are verrucae vulgares, erythematous hypertrophic scars, undesired hair
      growth, and wrinkled, photoaged facial skin.

PMID- 9199024
TI  - [Morphine metabolism--pharmacokinetics and pharmacodynamics].
AB  - With the increasing use of morphine, growing interest for the clinical
      implications of its metabolites, morphine-3-glucuronide (M-3-G) and morphine-6
      glucuronide (M-6-G) has emerged in the literature. M-6-G binds to the opioid
      receptor and has analgesic properties in man. Clinical studies have not delivered
      strong evidence of significant correlation between the concentration of morphine
      and its glucuronides in plasma and cerebrospinal fluid and pharmacodynamics such
      as analgesia. There is no clinical evidence to indicate that M-6-G has a
      pronounced respiratory depressing effect in man, while the literature contains
      conflicting reports with regard to other side-effects. M-3-G does not bind to the
      m-opioid receptor and consequently has no antinociceptive effects. Studies in
      rodents have shown that morphine, M-6-G and especially M-3-G may induce
      hyperalgesia, allodynia and myoclonus. It is assumed that these side effects are
      caused by a spinal antiglycinergic mechanism. The role of M-3-G in morphine
      antagonism and development of tolerance has not yet been settled. As M-3-G and M
      6-G are eliminated by the kidneys, renal insufficiency will lead to accumulation
      of these. Accordingly dosage should be reduced or other opioids be considered in
      such cases.

PMID- 9199025
TI  - [Renal insufficiency in myelomatosis. Prognostic factors and survival].
AB  - Clinical features, occurrence and reversibility of renal failure, response to
      treatment and survival duration in 190 multiple myeloma patients were reviewed in
      a retrospective study based on hospital records. Renal failure was present in 27%
      of the patients and constituted an important prognostic factor. Reversibility of
      renal failure occurred in 52% of the patients and was more frequent in those with
      low serum creatinine, hypercalcaemia, high erythrocyte sedimentation rate and
      high level of IgA. Response to chemotherapy resulted in a prolonged survival,
      whereas recovery of renal function did not significantly affect survival.

PMID- 9199026
TI  - [Intrauterine growth retardation and premature delivery. The effect of smoking
      and psychosocial factors].
AB  - The purpose of the study is to investigate the influence of psychosocial stress,
      maternal schooling, social support, psychological well-being, alcohol and smoking
      on intrauterine growth retardation and premature delivery. At a Copenhagen
      university hospital 2432 consecutive Danish-speaking women in 20th week of
      pregnancy completed a questionnaire including the General Health Questionnaire
      and Severity of Psychosocial Stressor Scale and questions about social network,
      education, smoking and drinking habits. In 212 cases (8.7%) the women delivered
      before day 259 of gestation. In a multiple logistic regression model, pre-term
      delivery proved to be associated with psychosocial stress and poor school
      education. In 152 cases (6.3%) infants had a birth weight below the defined 10th
      percentile. In a multiple logistic regression model, IUGR was associated with
      smoking. In preventive programmes, such as anti-smoking campaigns, it should be
      kept in mind that women who smoke are also the least educated and have the
      poorest support from a social network.

PMID- 9199027
TI  - [Thromboembolic complications after ambulatory herniotomy].
AB  - Thromboembolism is a serious complication of surgery and prophylaxis is therefore
      recommended. This study examines a new aspect of the problem, the incidence of
      thromboembolism after day-case surgery. From 1982 to 1992, 2281 patients
      underwent day-case repair for inguinal hernia management. Hospital admission for
      thromboembolism within the first 30 days after surgery was identified by computer
      linkage to the National In-Patient register, which contains details of all
      hospital admissions in Denmark. One patient developed non-fatal pulmonary
      embolism. No other patients were admitted to hospital with venous thromboembolism
      within 30 days of herniorrhaphy. It is concluded that there is no need for
      routine prophylaxis for thromboembolism in day-case hernia surgery.

PMID- 9199028
TI  - [Patients with early stages of endometrial cancer should be spared adjuvant
      radiotherapy. Danish Endometrial Cancer Group].
AB  - In an attempt to create uniform nationwide guidelines for the management of all
      stages of endometrial carcinoma, and to limit the use of adjuvant radiation
      therapy in stage I disease to high-risk patients only, a protocol was developed
      by the Danish Endometrial Cancer group (DEMCA). From September 1986 through
      August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the
      endometrium have been treated according to this protocol. This figure represents
      all endometrial carcinomas diagnosed in Denmark during this two-year period. The
      primary treatment was total abdominal hysterectomy and bilateral salpingo
      oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no
      macroscopic residual tumour and/or microscopic tumor tissue in the resection
      margins was found following surgery. Based on surgery and histopathology, these
      patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n
      = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative
      radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III
      (Group 1) cases received external radiation therapy. Recurrence rate at 68-92
      months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk,
      30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17
      vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61
      months). In this population-based investigation it has been shown that P-stage
      low-risk patients are adequately treated by total abdominal hysterectomy and
      bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation
      therapy is necessary.

PMID- 9199029
TI  - [Hysterectomy in a Danish population. Weight-related factors, psychological
      factors and life style variables].
AB  - The aim was to assess risk factors for hysterectomy performed for benign
      conditions. In a prevalence study, 2301 Danish women were selected at random in
      1982. Information about weight and slimming history, life-styles, psychological
      factors, gynaecological history, and social background were obtained. In an
      incidence study, the cohort was followed from 1982 to 1990 to assess the
      incidence of hysterectomy. In the prevalence study, weight cycling (recurrent
      weight loss and weight gain of more than 5 kg) was associated with hysterectomy
      for benign disease (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.99)
      independently of overweight, smoking, oral contraceptives, psychological and
      social factors. In the incidence study, weight cycling was the only significant
      weight-related risk factor for hysterectomy performed for benign disease
      (adjusted relative risk 2.49, 95% confidence interval 1.10-5.60), explaining the
      relation between hysterectomy and psychological factors. Weight cycling might be
      an important risk factor for premenopausal hysterectomy performed for benign
      conditions.

PMID- 9199030
TI  - [Should recurrent Cytomegalovirus infections in patients with liver
      transplantation be treated?].
AB  - Cytomegalovirus (CMV) is the single most important viral pathogen in organ
      transplantation. Treatment strategy for CMV infection and disease is not well
      established in transplantation. We report a case of primary CMV infection and two
      relapses in a woman with a liver transplant in whom spontaneous clearing of the
      second CMV relapse was seen. A 23 year-old CMV-seronegative woman received a
      liver transplant with a CMV-negative organ. Six weeks after transplantation she
      had her primary CMV infection proved by seroconversion and virus isolation. She
      had no clinical symptoms. Treatment with ganciclovir for five weeks resulted in
      declining CMV-antigen positive cells from 300/200.000 PMNs to CMV-antigen
      negativity. Only a slight antibody response was seen. At week 13 the first
      relapse occurred evidenced by antigenaemia. Ganciclovir was reinstituted for six
      weeks resulting in reduced antigenaemia. At week 22 liver biopsy was performed
      due to slightly elevated ALAT. The biopsy showed evidence of focal CMV hepatitis
      and blood analysis showed 120 CMV-antigen positive cells/200.000 PMNs. In spite
      of this, ganciclovir was not reinstituted, but the immunosuppressive treatment
      was reduced to a minimum to stimulate the patient's immune response to CMV.
      During the following months the patient gradually developed IgG antibody, cleared
      the antigen and levels of liver enzymes returned to normal. We suggest that
      ganciclovir treatment, may be omitted in cases of relapse with minimal clinical
      symptoms, slight antigenaemia and a beginning antibody response and that, the
      immunosuppressive treatment should be reduced instead. Such an approach requires
      careful clinical monitoring of the patient.

PMID- 9199031
TI  - [Osteochondritis dissecans of the acetabulum].
AB  - A case of osteochondritis dissecans (OD) of the acetabulum in a 14-year-old girl
      is presented. The initial clinical manifestation was hip pain and restricted
      movements of the joint. Magnetic Resonance Imaging confirmed the diagnosis. The
      patient was treated conservatively, using crutches. One year after the first
      examination, no clinical improvements were found. X-rays of the hip showed
      increased sclerosis around the osteochondritis-segment, indicating incipient
      healing. The patient is still conservatively treated, with regular clinical
      examinations. The diagnosis should be remembered in the case of patients with
      unexplained hip-pain, and may require magnetic resonance imaging for
      confirmation.

PMID- 9199032
TI  - [Better health for mother and child. A nation-wide study of pregnant women and
      newborn infants].

PMID- 9199033
TI  - [Is the Ugeskrift for Laeger a scientific journal or a forum for an exclusive
      group of physicians?].

PMID- 9199034
TI  - [Vesico-renal reflux].

PMID- 9199035
TI  - [Renal cell carcinoma].

PMID- 9199036
TI  - [Status of organ preserving surgery in renal cell carcinoma].
AB  - Nephron-sparing surgery in renal cell carcinoma is an accepted approach in
      patients with bilateral carcinomas, solitary kidneys and in patients with chronic
      renal failure in whom radical nephrectomy would necessitate immediate renal
      replacement therapy (mandatory indications). Because of the improvement of
      operative techniques-like renal perfusion in hypothermia or work-bench surgery
      over 95% of patients can spared dialysis even if multiple tumors or locally
      advanced renal cancer is present. Based on the excellent outcome of nephron
      sparing surgery in mandatory indications (5-year survival rates over 80%),
      several centers advocate extending the use of partial nephrectomy to selected
      patients with a normal opposite kidney (elective indications). Several reports on
      nephron-sparing surgery in elective indications with a median follow-up time of
      40 months document similar survival rates compared to radical nephrectomy.
      Nevertheless, due to the low incidence of bilateral renal carcinomas (under 2%),
      only 2 of 100 patients would benefit from this approach. Furthermore, local
      recurrence after nephron-sparing surgery occurs mostly after 4 years (late
      recurrence); therefore, it seems doubtful whether the short follow-up times
      really reveal the the true recurrence rate. The prognosis after development of a
      local recurrence is poor.

PMID- 9199037
TI  - [Renal cell carcinoma with vena cava involvement. Surgical strategies and
      results].
AB  - The elaboration of new operative procedures established in the last decade has
      led to an improved prognosis in patients with renal cell carcinoma with vena
      caval extension. We report on our personal operative experience in over 100
      patients and present the current analysis of 76 patients with renal carcinoma
      with vena caval extension seen in our institution between 1985 and 1996. Sixty
      six patients underwent nephrectomy and removal of vena caval tumor thrombi.
      Actuarial 5-year survival for patients without metastasis was 38%. For patients
      with tumor stages between I and III, 5-year survival was between 40 and 50% and
      was not significantly related to the rostral extent of the tumor thrombus. The
      relatively poor outcome for patients with tumor thrombi invading the right atrium
      was caused by a high perioperative mortality (50%). For patients with distant
      metastases, medium survival time was 10.5 months, implying that radical surgery
      is useless in cases of distant metastases.

PMID- 9199038
TI  - [Brain metastases in renal cell carcinoma. Results of treatment and prognosis].
AB  - Brain metastases develop as a late manifestation of renal cell cancer (RCC) and
      pose an increasing challenge to urologists as a result of the more frequent
      prolonged survival of patients with advanced RCC. Therapeutic options, including
      surgical resection and radiotherapy, were analyzed retrospectively to assess
      survival and to identify factors influencing prognosis in a group of 90 patients
      treated either by brain metastasectomy (n = 64) or radiotherapy (n = 26). The
      analysis confirmed that the overall median survival was a disappointing 461 days
      and the 1-year survival rate was 31% for patients treated by surgical resection
      and 310 days and 15% respectively for patients treated by radiotherapy. However,
      a subgroup of patients who, benefitted significantly from aggressive treatment of
      metastases could be defined. The following favorable prognostic factors showed a
      trend toward improved survival: (1) metachronous appearance of brain metastases
      more than 1 year after nephrectomy (P < 0.0001), (2) good patient performance
      (Karnofsky > 70) (P < 0.0002), (3) patient's age under 50 years (P < 0.05), (4)
      solitary lesions (P < 0.05), (5) minimal or no neurological deficit (P < 0.05),
      and (6) the absence of/or minimal extracranial metastases (P < 0.05). No
      influence of lesion size and localization (infratentorial vs supratentorial) on
      survival was detected. Surgical treatment of recurrent brain tumors (n = 17)
      yielded and additional median survival advantage of 8 months as compared to
      untreated patients (n = 16). Our results suggest that, especially in patients
      with good prognostic criteria, a radical metastasectomy plus vigorous surgery of
      local recurrences and, if required, subsequent systemic immuno- or
      chemoimmunotherapy should be performed. In patients with poor prognosis,
      stereotactic radiosurgery is recommended for palliation and survival
      prolongation.

PMID- 9199039
TI  - [The clinical significance of renal cell carcinoma in dialysis dependent patients
      in comparison with kidney transplant recipients].
AB  - The clinical relevance of de novo Renal Cell Cancer was compared in chronic
      hemodialysis patients and renal allograft recipients. Clinical course of these
      patients was followed for 15 years. 21 of 788 patients who underwent radical
      nephrectomy were suffering from renal insufficiency at the time of surgery.
      Evaluated data included clinical symptoms; tumor histology and clinical course.
      19 patients received chronic hemodialysis treatment. 7 patients demonstrated
      stable function of the allograft. 92% of patients receiving hemodialysis
      treatment did not show metastasis and none died of renal cell carcinoma. On the
      contrary, 71% of patients who underwent renal transplantation showed advanced
      tumor disease or metastasis. 3 patients have died of RCC. Aggressive tumor growth
      of RCC requires close follow up in patients who received a renal allograft.

PMID- 9199040
TI  - [Immunotherapy of metastatic renal cell carcinoma. Is clinical use justified in
      view of outcome, side effects and costs?].
AB  - The immunogenic potential of renal cell carcinoma and the resistance of its
      metastases against chemotherapy, radiation and hormonal treatment have led to the
      development of a great number and variety of different strategies, summarized
      under the term immunotherapy. Objective remissions can be expected in about 20
      40% of patients. Another 30-40% show stable disease for a limited time, only
      occasionally for longer. Most results are from uncontrolled phase II studies. A
      cancer cure can usually not be expected, long-term remissions are rare (5%), and
      high remission rates are only observed in studies with strong patient selection.
      Some authors have reported a higher survival rate in patients treated with IL-2
      or IFN. Survival of patients with objective remissions is significantly improved.
      A standard therapy cannot be defined. Even presuming an increased survival rate,
      the toxicity, which can lead to a dramatic reduction in quality of life, and the
      high costs have to be considered carefully. We think that in view of the lack of
      therapeutic alternatives, the improving efficacy, the potential survival benefit,
      the reduction of toxicity and the perspectives, immunotherapy is essential in the
      treatment of metastatic renal cell carcinoma. Its use should be confined to
      clinical studies.

PMID- 9199041
TI  - [Influence of DNA ploidy and grading on survival in primary metastatic prostate
      carcinoma].
AB  - An aneuploid pattern of prostatic cancer defined by flow cytometry was shown to
      be of value in predicting progression rates and patient survival times. We
      evaluated the long-term value of DNA analysis in prostatic cancer in 61 patients
      with advanced disease. We performed flow cytometry on 61 fresh prostate specimens
      obtained-from a transrectal needle biopsy or a transurethral resection. All
      patients received antihormonal therapy. Time until death was evaluated in all
      patients. Of the DNA histograms analyzed, 37% showed a diploid pattern, 63% an
      non-diploid pattern, and 37% a tetraploid or hypertetraploid pattern. Kaplan
      Meier plots were generated for analysis of the probability of survival. Mean
      survival time was 44 months for patients with diploid (range 1-126 months) and 40
      months for patients with non-diploid tumors (range 1-96 months). This difference
      is not statistically significant. However, the combination of non-diploid and low
      differentiated (G3) tumors reduced survival time significantly (mean 20 months,
      range 1-62 months). There was no patient with combination of a diploid and highly
      differentiated tumor.

PMID- 9199042
TI  - [Urologic tumors in Germany. Initial data of 56,013 cases from clinical cancer
      registers].
AB  - Since 1985 a special work group involved in the coordination of hospital cancer
      registries in Germany (AKKK) has been collecting, storing and analysing data on
      tumour patients, received from cancer centres, oncological departments and
      specialised practices. The documentation of tumour patients is based, among other
      things, on information concerning localisation, histological findings and tumour
      spread. The data are stored in a central database administered by the work group.
      At present it contains data on approximately 500,000 oncological patients. In the
      period from 1987 to 1992, 56,013 initial entries were made concerning patients
      with urological tumours. Of these cases, tumours of the kidney (n = 11,424)
      constituted 20.4%. In 94.6% of the cases, histological investigation revealed a
      renal cell carcinoma-pT1: 5.8%; pT2: 53.6%, pT3: 37.2% and pT4: 3.4%. Tumours of
      the urinary bladder (n = 16,246) constituted 29.0% of all urological tumours. In
      93.8% of the cases a transitional cell carcinoma was detected-pTis: 1.0%; pTa:
      36.9%; pT1: 29.6%; pT2: 16.9%; pT3: 11.4%; pT4: 4.4%. Transitional cell
      carcinomas of the ureter or of the collecting system (n = 1,846) constituted 3.3%
      of the cases. The proportion of testicular tumours (n = 6,594) amounted to 11.8%;
      53.6% of these germ-cell tumours (n = 6,281) were seminomas and 46.6% were non
      seminomas. In all, 66.3% of the cases were lymph-node negative. Tumours of the
      prostate (n = 19,903) constituted 35.5% of the cases. In the period from 1987 to
      1992, the proportion of lymph-node-positive prostate carcinomas decreased from
      39.8% to 16.2%. The detailed analysis of these data shows how the hospital cancer
      registries can support the discussion regarding diagnosis and therapy of
      urological tumours.

PMID- 9199043
TI  - [Long-term results of wall stent implantation in benign prostatic hyperplasia and
      high risk status].
AB  - The implantation of a Wallstent prosthesis is a minimally invasive alternative to
      conventional TUR-P for the treatment of infravesical obstruction owing to benign
      prostatic hyperplasia. We report on the long-term follow-up of 37 patients with a
      high-risk status for TUR-P who have been implanted since May 1990. The ASA status
      was: ASA I: 0, ASA II: 2, ASA III: 17 and ASA IV: 18 patients. The median follow
      up is now 38.5 months. Directly after implantation, a medium increase in the
      maximum flow-rate from 7.5 ml/s to 16.9 ml/s was documented. Residual urine was
      reduced from 120 to 24.2 ml on average. After 12, 18, 24 and 36 months, average
      maximum flow rates of 16.1, 16.7, 12.0 and 11.6 ml/s were evaluated. The
      corresponding residual urine was 50.3, 121.1, 56.8 and 65 ml, respectively. Also,
      micturition frequency decreased from 12.4 preoperatively to 8.3, 7.6, 8.0, and
      8.4 per day on average. Nearly all patients reported perineal discomfort in the
      1st weeks after implantation. For this reason, the stent had to be removed in 1
      patient on the 45th postoperative day. In addition, a dislocated stent had to be
      replaced in 2 patients. Six of 15 retention patients presented with persisting
      detrusor dysfunction after implantation and were therefore discharged with a
      suprapubic tube. Endoscopic controls showed complete urothelial coverage in 78%
      of our patients after 6 months. After 18 months all stents were completely
      covered. Long-term follow-up showed reobstruction in 6 of 37 patients (16.7%) and
      signs of incontinence in 4 of 37 (10.8%). The late complication rate is therefore
      calculated at 27.5%. Stent-related deaths could not be found. We conclude that
      Wallstent implantation into the prostatic urethra is an alternative to TUR-P for
      patients at high risk from surgery. The good postoperative results also remain
      stable during long-term follow-up.

PMID- 9199044
TI  - [Treatment and follow-up of patients with squamous epithelial carcinoma of the
      penis].
AB  - Since squamous cell carcinoma of the penis is rare, prospective trials do not
      exist. Therefore, new treatment strategies have to be developed. Based on our
      experience with the treatment of 22 patients with penile squamous cell carcinoma,
      we describe our therapeutic approaches. Ten patients with superficial disease (T1
      2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to
      90%. In patients with extensive disease (T3-4 or N1-3) a partial or total
      penectomy was performed. After initial antibiotic therapy for 4 weeks, patients
      underwent inguinal lymph-node dissection and if the nodes were positive,
      additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph
      node metastases surgical resection was performed, covering the wound with a
      musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n =
      1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and
      with T3-4N1-3 (n = 8) 25%. Patients with distant metastases received inductive
      systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective
      responses occurred in 22% (1 CR, 1 PR) of 9 patients. These results suggest that
      immediate radical surgery with lymph-node dissection is the best treatment for
      squamous cell carcinoma of the penis.

PMID- 9199045
TI  - [Post-traumatic priapism in a 10-year-old boy].
AB  - The case of a 10-year-old boy with post-traumatic priapism after perineal trauma
      is presented. Interdisciplinary treatment using angiography and selective
      catheter embolization for juvenile high-flow priapism is demonstrated. The
      literature and the diagnostic possibilities resulting from color duplex
      sonography are discussed.

PMID- 9199046
TI  - [Transurethral laser ablation of the prostate in high risk patients with
      obstructive benign prostatic hyperplasia. Perioperative morbidity and 6 month
      outcome in 72 patients].
AB  - Between November 1993 and September 1995, we carried out visual laser ablation of
      the prostate (VLAP) in 72 high-risk patients (ASA 3-4; severe cardiovascular
      and/or pulmonary diseases) aged 60-88 years (mean 76.7 years); the prostate
      volume was 22-136 ml (mean 56 ml). The urinary peak flow rates (Qmax.) ranged
      from 2 to 15 ml/s (mean 4.4 ml/s) preoperatively; 42 patients (58.3%) suffered
      from acute urinary retention for up to 2 weeks and had an indwelling catheter.
      The residual urinary volume (RUV) was 0-320 ml (mean 142.3 ml) in those 30
      patients with spontaneous micturition. The International Prostate Symptom Score
      (IPSS) ranged from 10 to 33 (mean 21.8). In the first 37 patients, pressure-flow
      studies were carried out only in cases of doubt to verify obstruction. In the
      last 35 patients, pressure-flow studies were carried out in every case.
      Perioperatively, there was no appearance of blood loss of absorption of
      irrigation fluid. None of our patients needed transfusions or intensive care
      perioperatively. Further complications were not severe and could be handled
      without problems. In two patients with large benign prostate hypertrophy (BPH) a
      second operation (VLAP, no conventional transurethral prostatectomy) was
      necessary. After 6 weeks, 29.4% of the patients suffered from symptomatic urinary
      tract infections (UTI). After 6 months, only 7.1% of the patients had symptomatic
      UTI. After 6 weeks (n = 61), Qmax. was 6-34 ml/s (mean 15.3 ml/s), RUV was 0-230
      ml (mean 51.5 ml), and the IPSS was 12.3 (8-28). After 3 months (n = 54), Qmax.
      was 9-45 ml/s (mean 19.8 ml/s), RUV was 0-96 ml (mean 31.6 ml), and the IPSS was
      1-23 (mean 7.4). After 6 months (n = 52) Qmax. was 12-33 ml/s (mean 20.4 ml), RUV
      was 0-53 ml (mean 26.4 ml), and the IPSS was 1-12 (mean 4.1). VLAP provided no
      further risks for our high-risk patients, while Qmax., RUV, and IPSS were
      improved noticeably (improvement of more than 75%). It represents a step forward
      in the treatment of obstructive BPH in high-risk patients. Particularly in high
      risk patients with cardiac diseases, this procedure lessens the perioperative
      risk. Despite the minimal appearance of UTI after 6 months, UTI seemed to be the
      most important complication during the first few weeks after VLAP by virtue of
      the bothersome symptoms.

PMID- 9199047
TI  - [Magnetic resonance urography. First clinical results].
AB  - We report our preliminary results using a new magnetic resonance imaging
      technique for visualization of the urinary tract. Using the paramagnetic contrast
      medium gadolinium diethylene triamine penta-acetic acid (DTPA), we were able to
      obtain images of the urinary tract comparable to those obtained by conventional
      excretory urography. The major advantage of our technique is that besides good
      morphologic visualization, the excretion of gadolinium-DTPA can be studied
      simultaneously. We demonstrate our preliminary results in selected cases.

PMID- 9199049
TI  - [Radiation exposure in digital micturition cystourethrography in children. How
      much exposure by fluoroscopy?].
AB  - OBJECTIVE: Determination of the proportion of the dose-area product caused by
      fluoroscopy at voiding cystourethrography in children, using digital image
      intensifier technology. PATIENTS AND METHODS: Using computer-assisted dosimetry,
      we determined the dose-area product and the respective proportions of the dose
      area product caused by fluoroscopy and radiography as well as the number of
      radiographs taken at a given examination of 40 children (8 children less than 2
      years old, 15 children between 2 and 6 years old and 17 children between 6 and 15
      years old). RESULTS: The computer software program correctly differentiated
      between fluoroscopy and radiography in 80% of cases. Incorrect results were
      primarily observed in newborns and young children. The total radiation dose
      ranged in relation to patient age from 22 to 651 cGy x cm2. Fluoroscopy was
      responsible for an average 78% of the applied radiation dose. CONCLUSION:
      Computer-assisted dosimetry is useful in determining the proportion of the dose
      area product caused by fluoroscopy in older children undergoing voiding
      cystourethrography. When image intensifier technology is used, this accounts for
      more than 75% of the total radiation dose. The method is not suitable for use in
      small children.

PMID- 9199048
TI  - [Microsurgical testicular denervation as therapy option in chronic testalgia].
AB  - Chronic testicular pain represents a challenging urological chronic pain syndrome
      in terms of adequate diagnosis and therapy. Reported success rates of 55-73% and
      10-40% of conservative and surgical interventions are extremely low. We report on
      microsurgical testicular denervation as therapeutic option in patients with
      chronic testicular pain (CTP). 12 consecutive patients with CTP were included in
      our study. After complete diagnostic workup and positive response to testicular
      nerve blockade, all patients underwent surgery: the cremasteric muscle was
      dissected by electrocautery, the periadventitial layer of the testicular artery
      was dissected over a length of 2-3 cm. After a median follow-up of 20.6 months (4
      62) 11/12 patients (92%) are pain free. None of the patients suffered from intraa
      or postoperative complications. Based on our experience microsurgical testicular
      denervation should be performed in patients with CTP and no underlying organic
      disease. However, the high success rate of our surgical procedure can only be
      maintained if the selection of suitable patients is performed very carefully and
      a specific organic origin of CTP has been excluded prior to surgery.

PMID- 9199050
TI  - [X-ray diagnostic features of giant bleeding ulcers in stomach and duodenum].
AB  - The study was based on the analysis of clinical, X-ray, and morphological
      examinations made in 64 patients with giant gastric and duodenal ulcers. All the
      patients were admitted for gastroduodenal hemorrhage. Among the examinees, there
      were 28 patients with giant ulcer of the stomach and 26 with that of the
      duodenum. The authors present the methods of X-ray examinations and the X-ray
      symptomatology of giant ulcers of the stomach and duodenum. Gastroscopic and X
      ray examinations were comparatively analyzed. The paper gives evidence that the X
      ray examination has many advantages in estimating the size and ratio of ulcers to
      the adjacent organs and tissues. The paper outlines giant duodenal ulcers. The
      authors identify two groups of patients with giant ulcers of the duodenal bulb,
      which differ in its size and the extent of deformity. One of valid signs of the
      penetration of giant ulcers is not only their size, but their depth and fixation
      to the adjacent organs and tissues.

PMID- 9199051
TI  - [Transabdominal ultrasound study of stomach and duodenum: standardization and
      potentialities].
AB  - The paper presents an original procedure for transabdominal ultrasound
      examination of the stomach and duodenum, which yields an objective piece of
      information on the status of all wall layers of the above organs. The procedure
      is rather easy-to-use, noninvasive, and well tolerable. Its efficiency is
      confirmed by the date of examination of 46 patients.

PMID- 9199052
TI  - [Computed tomography in the diagnosis of salivary gland neoplasms].
AB  - To evaluate the efficiency of computed tomography (CT) in the diagnosis of
      salivary neoplasms, 68 patients (50 with benign tumors of the salivary glands, 10
      with theirs malignant tumors, 8 with salivary cysts) were examined. The authors
      revealed the high informative value of CT in the diagnosis of salivary bulky
      lesions. CT defined the site of a tumor, the benign or malignant pattern of its
      growth, the extent of tumorous invasion. The diagnostic value of CT in the
      diagnosis of salivary glands was as follows: its sensitivity, specificity, and
      accuracy were 97.0, 81.8, and 94.9%, respectively.

PMID- 9199053
TI  - [Radiation diagnosis of spleen diseases].
AB  - The paper deals with the diagnosis of splenic diseases by using the currently
      available techniques. Based on the examination of a large group including 391
      patients with various benign and malignant splenic diseases, the authors showed
      that despite the fact that primary diseases of the spleen are comparatively
      rarely encountered, nevertheless, early diagnosis of its lesions is of great
      importance for the diagnosis of various systemic diseases and abnormalities of
      primary organ processes. Based on the data available in the literature and their
      own findings, the authors concluded that at the earliest stages of their
      preclinical development, splenic tumors can be now diagnosed by a complete
      package of up-to-date diagnostic tools. Ultrasonic and computerized tomographies
      are of the highest informative value. However, diagnostic puncture is required in
      some cases. The paper details the semiotics of a wide range of splenic
      pathological processes by applying all currently available techniques of
      radiation diagnosis.

PMID- 9199054
TI  - [Present day radiation diagnosis of renal tumors and cysts].
AB  - The paper discusses the present-day radiation diagnosis of renal bulky
      formations: tumors and cysts. Based on the study of a great body of clinical data
      on 708 patients, the authors showed the potentialities of routine X-ray and
      currently available radiation techniques in the diagnosis of benign and malignant
      tumors and cysts of the kidney. Based on the data available in the literature and
      their own findings, the authors concluded that at the earliest stages of their
      preclinical development, tumors can be today diagnosed by a complete package of
      up-to-date diagnostic tools. Ultrasonic and computerized tomographies are of the
      highest informative value in diagnosing tumors and cystic formations. However, in
      some cases, a diagnosis is made via a routine excretory urography, angiography
      and needle biopsy. Excretory urography is of limited value for the diagnosis of
      renal bulky formations and it is used as an auxiliary mainly when a pathological
      process takes place in the renal hilus area. Angiography retains its significance
      as a supplementary technique. In the vast majority of cases, an accurate
      nosological diagnosis can be made on the basis of evaluation of the pattern of
      blood supply (the presence of abnormal vessels and their topographic features).
      The paper details the semiotics of a wide range of renal bulky processes by
      applying all currently available techniques of radiation diagnosis.

PMID- 9199055
TI  - [X-ray endoscopic semiotics and diagnostic algorithm of radiation studies of
      preneoplastic gastric mucosa changes].
AB  - The X-ray endoscopic semiotics of precancerous gastric mucosal changes
      (epithelial dysplasia, intestinal epithelial rearrangement) was examined by the
      results of 1574 gastric examination. A diagnostic algorithm was developed for
      radiation studies in the diagnosis of the above pathology.

PMID- 9199056
TI  - [Symptom of asymmetric bladder filling defect in the presence of ureteral
      prevesical calculus].
AB  - Examining descending cystograms in 357 patients with renal colic caused by
      calculi in the ureteral prevesical portion revealed that 34 (9.5%) had the
      asymmetric bladder filling defect which was ipsilateral to the calculus. In 11
      patients with the calculi strangulating in the ureteral ostium, the outlines of
      filling defect took the form of a rim around the calculus. Echography provides
      direct ultrasonic evidence for a calculus in 186 (52%) patients and the
      asymmetric shape of the bladder only in 1 patient. The described symptom caused
      by urinary detrusor spasm and, in some cases, by perifocal tissue edema at the
      site of the ureteral ostium with its strangulated calculus may serve as indirect
      evidence for a lower ureteral calculus.

PMID- 9199057
TI  - [Use of ultravist to examine the gastrointestinal tract in patients with
      emergency abdominal pathology].
AB  - The paper deals with the results of using the nonionic water soluble contrast
      agents ultravist 300 and ultravist 370 (Schoring, Germany) to examine the
      gastrointestinal tract (GIT) in 21 patients with acute abdominal abnormality. GIT
      contrasting was made in 9 patients in the early postoperative period and in 12
      patients on their admission to the Institute. The examinations revealed the high
      contrast rate of the above agent when administered into the stomach and upper
      small intestine, which excluded failure of gastroenteroanastomic sutures and the
      sutured gastric wall in 2 patients, established, in terms of gastric displacement
      and deformity, left-sided subdiaphragmatic abscess, and in terms of transposition
      of a portion of the gastric fornix into the pleural cavity, rupture of the left
      diaphragm, and to exclude diaphragmatic rupture with closed abdominal injury. The
      revealed important quality of ultravist within a short time (1-2 hours) to
      contrast the small intestine and enter the colon enabled differential diagnosis
      to be made between complete and partial small intestinal ileus and between early
      comissural small intestinal ileus and postoperative intestinal paresis. Ultravist
      contrast studies allowed the authors to avoid an emergency operative intervention
      and to follow up the resolution of ileus during medical therapy.

PMID- 9199058
TI  - [To diagnosis of giant hepato-choledochal cysts].

PMID- 9199060
TI  - [Medical professional policy--possibilities and outlook].

PMID- 9199059
TI  - [Potentialities of present day computed tomography in diagnosis of stomach
      cancer].
AB  - Based on the findings of 206 examinations, the authors advance their opinion of
      the role of X-ray computed tomography (XRCT) in the diagnosis of gastric cancer.
      The authors think that if their developed procedure for X-ray computed tomography
      based on the use of usual air as the only contrast agent by measuring it out in
      doses and administering into the gastric at CT scanning, which is called
      pneumoroentgenocomputered tomography (PRCT), is employed, it, preserving all the
      traditional, already known, advances of XRCT additionally yields highly valuable
      information on a direct damage to the gastric wall itself. The findings suggest
      that PRCT is especially effective in intramurally growing gastric cancers, the so
      called squamous carcinomas, which are hardly differentiated for diagnosis and
      which are most common. Noteworthy is the fact that in seemingly unquestionable
      exophytic gastric cancer, detecting intramural tumorous infiltration adjacent to
      the exophyte, PRCT thus provides evidence that the exophyte revealed is the
      peculiar top of an iceberg, whose base shows a significant exophytic gastric
      carcinoma.

PMID- 9199061
TI  - [Dysplasia and therapy factors in hip developmental disorders].

PMID- 9199062
TI  - [Orthopedic surgery in HIV-positive patients in Zambia].

PMID- 9199063
TI  - [Exercise therapy in postural weakness].

PMID- 9199064
TI  - [COX-2 inhibition: latest on NSAID].

PMID- 9199065
TI  - [Juridical and professional requirements for the acknowledgement of occupational
      diseases].

PMID- 9199066
TI  - [Science and economy in orthopedics and physiotherapy].

PMID- 9199067
TI  - [Age-related force distribution at the proximal end of the femur in normally
      growing children].
AB  - In a group of normally developed children and adolescents the age dependent
      distribution of forces at the proximal end of the femur was to be described. The
      results should explain why the shape of the proximal end of the femur changes
      significantly during the time of growth and why the neck shaft angle decreases.
      The method applied was the biomechanical computation analyzing in the coronal
      plane according to Pauwels' biomechanical hip model. The necessary age relevant
      data was derived from 675 anteroposterior pelvis radiographs of healthy children
      of both sexes and of varying age. The following can be put down as a result: 1.
      The proximal end of the femur is stressed by two resultant forces: the hip
      resultant force R controls the growth of the capital growth plate, the
      trochanteric resultant force RT regulates the growth of the greater trochanter
      growth plate. 2. During the growing period the hip resultant force R adjusts
      itself less vertically: during the second year of life it inclines at an average
      of 11,6 degrees towards the vertical, towards the end of the growing period it is
      incident with an inclination angle of 20 degrees. With the older child the
      magnitude of the hip resultant force R decreases in relation to the exerting body
      weight. 3. During the time of growth the trochanteric resultant force RT
      maintains its direction stability with inclination angles of 50-52 degrees
      towards the vertical. Its magnitude increases significantly (in relation to the
      exerting body weight). 4. From age 2 to 10 the projected neck shaft angle
      decreases from an average of 148.2 degrees to 133.7 degrees and usually remains
      stable. It can be concluded that the shape of the proximal end of the femur is
      determined by the muscle forces stimulating the greater trochanter apophysis and
      by gravity. With increasing age the growth of the greater trochanter apophysis
      shifts the insertions of abductor muscles laterally. As a result the directions
      of the hip abductors and the hip resultant force R incline. The neck shaft angle
      decreases consecutively.

PMID- 9199068
TI  - [Intertrochanteric flexion osteotomy and allo-arthroplasty in femur head
      necrosis. A comparative retrospective study].
AB  - Intertrochanteric flexion osteotomy and total hip arthroplasty are the most
      frequent operative treatments of advanced osteonecrosis of the femoral head in
      adults. In a retrospective study the postoperative results of intertrochanteric
      osteotomy and total hip arthroplasty were determined in 68 cases. The evaluation
      was based on the modified Harris-Hip-Score, the clinical examination and the
      radiological classification of the ARCO. The patients after osteotomy showed
      significantly worse subjective results. After osteotomy an increase of the stage
      of osteonecrosis was found in 73% of the patients. There was no correlation
      between clinical result and radiological stage of osteonecrosis. In spite of a
      better preoperative situation the results after osteotomy compared to hip
      arthroplasty were disappointing in many cases. The postoperative result did not
      depend on the preoperative stage of the osteonecrosis. The new classification
      system of the ARCO, which includes the very important MRI, proved to be very
      suitable and practicable. Based on our results it seems to be reasonable, to
      restrict the indication for intertrochanteric flexion osteotomy to cases of low
      stage osteonecrosis and carry out cementless total hip arthroplasty primarily in
      all others.

PMID- 9199069
TI  - [Reproducibility in the roentgenological assessment of coxarthritis].
AB  - The "German Society of Orthopaedic Surgery and Traumatology (DGOT)" is trying to
      support the application of standardized and reproducible criteria in diagnosis
      and therapy of osteoarthritis. As radiographs are a primary measure of outcome at
      present, the objective of this study was to investigate the reproducibility of
      radiologic assessment in hip osteoarthritis using different radiographic
      variables. 3 investigators read 100 hip joints on 50 pelvis radiographs at two
      time-points for the presence and severity of individual radiographic features:
      joint space narrowing (JSN), osteophytes, sklerosis, subchondral cysts and
      deformity of the femoral head. Additionally the summary grade of Kellgren and
      Lawrence (1963) and Scott et al (1992) was assessed. Intra- and inter-rater
      reliability were calculated by intra-class-correlation-co-efficient (ICC). The
      results regarding intra- and inter-rater-reliability show excellent values for
      superior JSN, femoral head deformity and the summary score. The radiologic
      assessment of medial JSN, osteophytes and acetabular sklerosis depends on the
      level of the investigator's experience. Perifoveal osteophytes and subchondral
      cysts do not seem to be have sufficient reproducibility. The results of our
      investigation show, that a reliable radiological classification of the severity
      of hip osteoarthritis is possible by assessment of certain individual
      radiographic features or a summary grade.

PMID- 9199070
TI  - [Retrospective study on femoral neck lengthening osteotomy].
AB  - Our retrospect study refers to the problem of improved flexibility of the hip
      joint, elongation of the leg as well as decrease of pain. Patients suffering from
      Coxa vara, a high positioned Trochanter and a short neck of the femur underwent
      triple osteotomy with a distal transposition of the Trochanter major. All 8
      patients had a thorough clinical (according to the scheme by Merle de Aubigne)
      and radiological postoperative checkup. The results were analyzed and showed an
      average increase of the length in leg of 1.9 cm and and average increase of
      capacity of abduction of 11 degrees. From these findings we draw the conclusion
      that triple osteotomy operation should be performed only on patients whose hip
      joints are free from arthrosis or show only insignificant symptoms of arthrosis.

PMID- 9199071
TI  - [Validity and reproducibility of osteodensitometric DEXA-measurements following
      total hip endoprosthesis].
AB  - For the determination of reproducibility of bone densitometric measurements we
      performed a measurement according to the DEXA- method. 35 patients after
      implantation of total hip replacement were examined with a Lunar DPX-L. We
      received a maximum reproduction error of 1.2% according to the GRUEN-analysis.
      The operated hip of 17 patients showed an increase in bone density between 5 and
      18% by the implantation of an arthroplasty compared to the preoperative values.
      The non-operated prosthesis-corrected hip showed a reproduction error of 3.8% in
      ROI 1 in 17 patients, otherwise a maximum of 1.3%. Considering an interfemoral
      difference in bone density of up to 20%, differences in periprosthetic bone
      density of up to 40% compared to the contralateral side can be within the normal
      range in a retrospective measurement. Therefore retrospective determination of
      bone density after cementless hip arthroplasty only is of limited value. Only
      prospective analysis can provide reliable information about the actual loss of
      bone density.

PMID- 9199072
TI  - [Dislocation of total hip endoprosthesis with special reference to various
      techniques].
AB  - 1238 primary total hip replacements for arthritis were performed in our hospital
      from 1980 until 1988. 26 dislocations (2.1%) were registered during this period.
      No differences became obvious regarding age, sex, type of prosthesis and
      different concepts of postoperative treatment. After the posterior approach
      dislocations occurred in 18 (3.1%) of the cases, 8 dislocations (1.2%) were found
      after the transgluteal approach. The dislocation rate was significantly higher
      for the posterior approach. Derotation braces were not able to decrease the risk
      of redislocation. Most of the dislocations happened during the first
      postoperative week. The most frequent occasions were rotation of the operated leg
      while lying in bed and deep sitting positions. Performing the posterior approach
      for primary total hip arthroplasty the surgeon has to realize the higher
      dislocation rate.

PMID- 9199073
TI  - [Cryotherapy as analgesic technique in direct, postoperative treatment following
      elective joint replacement].
AB  - The application of crushed ice or hydrogenated silicate, a micro-crystalline
      substitute has been used as a method to treat posttraumatic and postoperative
      irritations of the locomotor system for a long time. Closed systems using pumps
      can be viewed as further development as they enable continuous, water-free
      cooling of operating areas. The analgetic effect of postoperative cold therapy
      was evaluated in a prospective clinical trial, including 312 patients after total
      knee or hip arthroplasty. Conventional cold packs, consisting of microcrystalline
      silicate were compared to a continuous applicable closed system. Continuous
      cryotherapy resulted in a depression of skin temperature to 12 degrees C, whereas
      intermittent cooling only caused a mean temperature decrease of 1 degree C.
      Clinically continuous cold application leads to a more than 50% decrease of
      analgetic demands in both, systemic and regional application (p < 0.001). This
      observation was found in a significant correlation with patient's pain sensation
      as well as primary range of motion. Intermittent cryotherapy was found to be
      ineffective in postoperative pain relieve in hip- and adequate in knee
      arthroplasty patients. We could not report an influence on postoperative blood
      loss, as discussed in previous reports.

PMID- 9199074
TI  - [Comparison between low-molecular and unfractionated heparin in the prevention of
      thrombosis in patients with total endoprosthetic replacement of hip and knee
      joint].
AB  - PURPOSE: Thrombosis-prophylaxies with heparins after total hip arthroplasty (THP)
      and total knee arthroplasty (TKA) is well accepted. The aim of this study was to
      compare the low molecular weight heparin (Enoxaparin) with PTT adjusted
      unfractionated heparin (Na-heparin). METHODS: In a prospective study of 226
      patients after THA and TKA, we performed physical examination and ultrasound in
      compression and duplex technique one day before surgery and at the 7th and 14th
      day after surgery. 120 patients received Enoxaparin 1 x 40 mg per day in fixed
      dosage. 106 patients received Na-heparin 3 x 5000 IE. Since PTT did not reach 40
      seconds, Na-heparin dosage was increased to 3 x 7500 IE. RESULTS: The overall
      thrombosis rate was 4% (n = 9), in the Enoxaparin group 2.9% for the 70 THA and
      10% for the 50 TKA. Thrombosis occurred in the group of unfractionated heparin
      (PTT adjusted) in 1.8% after THA and in 2% after TKA. In TKA, there is
      statistical difference between the two heparin groups. CONCLUSION: In the
      thrombosis prophylaxis of TKA, PTT adjusted unfractionated heparin is superior to
      low molecular weight heparin in fixed dosage.

PMID- 9199075
TI  - [The Gottinger minipig as an animal model in hip endoprosthesis. Anatomy,
      anesthesia, operation results].
AB  - The Gottingen mini swine is a good experimental animal. The electrolytes and the
      bone healing rate is comparable to human. The weight of the animals should be 30
      45 kg. All surgery is performed under endotracheal general anaesthesia without
      any complication. There is minimal blood loss because blood pressure is only
      40/80 mmHg. We used the anterolateral approach. The feature peculiarity of this
      animal model are: 1. Skin incision should start 10 cm cranial to the tail and
      should be curved. 2. The osteotomy of the head is V-shaped in maximal external
      rotation. 3. The acetabulum is prepared with a 23.5 mm reamer. 4. The stem should
      be implanted first. After completion of the preliminary test operations, 10
      animals were operated in the described standard manner. During one year follow-up
      there was only one radiological cup-loosening.

PMID- 9199076
TI  - [Comparison of knee ligament scores and rating systems].
AB  - The results of the treatment of knee instabilities are evaluated by different
      scoring systems including subjective and/or objective criteria. Because of their
      number and their different criteria a comparison between the scoring systems is
      still a problem. The aim of this study was to analyze 14 different scoring
      systems and prove the comparison of the commonly used rating scales. 116 patients
      with anterior or anterior-medial knee instabilities were followed up at least 2
      years postoperatively. The evaluation was performed according to the criteria of
      the used rating-scales. The Lysholm I scoring system showed the highest mean
      total score (92 points). The scales that gave the highest correlation were the
      Cincinnati and ARPEGE scoring system (r = 0.97). The Lysholm I Scale and the
      Barrack Scale correlated least well (r = 0.711). This study documents that a
      transfer of results from one scoring system to another is not possible. A
      comparison between these scoring systems is only possible after adjusting the
      total points, the quality and the quantity of each criterion and component of the
      scoring system. This can done by using a standardized rating scale like the IKDC
      score.

PMID- 9199077
TI  - [Patellar hypertension syndrome--nomenclature, diagnosis and therapy].
AB  - PURPOSE: Complaints in the area of the patella have been abundantly described in
      the literature. However, a uniform nomenclature with regard to either diagnosis
      or therapy does not exist. METHODS: With the help of a standardized measuring
      method (intrapatellar pressure measurement and provocation test), it is possible
      to describe and classify patellar pain. An intrapatellar pressure increase over
      25 mmHg and/or a positive provocation test defines the term of Patella
      Hypertension Syndrome. RESULTS: Within a prospective study we carried out a
      special intraosseous drilling in 20 cases with the typical symptoms of the
      Patella Hypertension Syndrome. The drilling, which was carried out via the Hoffa
      fat body from distal, resulted in a distinct alleviation of symptoms in all cases
      and even in a complete absence of pain in most cases. This phenomenon was
      objectified by a pressure-check-up after 6 weeks, 6 months and 1 year following
      the drilling. In all 20 cases so far examined a decrease of between 40-70% of the
      original pressure level was achieved. In all cases the postoperative artificial
      pressure increase (provocation test) of the intraosseous pressure did not lead to
      the typical pain symptoms. CONCLUSION: We therefore have a relatively minor
      operation at our disposal enabling us to achieve an impressive therapeutic
      success, in cases where conventional treatment was neither causal nor successful.

PMID- 9199078
TI  - [Angiological complications following high tibial head correcting osteotomy--a
      case report].
AB  - Vascular complications following orthopedic procedures at the lower extremity are
      mainly thrombotic or thromboembolic events. Damages to vascular structures during
      operations close to the knee joint, like injuries of the popliteal artery, are
      extremely rare and receive a reserved consideration in the evaluation of
      postoperative complications. The extent of the vessel injury affects the grade of
      clinical symptoms-from acute arterial bleeding as far as slowly developing
      disturbances of haemodynamic, with effects to the different functions and pattern
      of the concerned tissues. Arterial bleeding into muscle compartments do not
      necessarily appear as an acute emergency, therefore it may occasionally be
      difficult to place the clinical symptoms into the right context of
      pathophysiological processes. In the present case a deep vein thrombosis of the
      affected extremity was initiated by a haemorrhage into the fossa popliteal and
      the compartments of the lower leg after injury of the popliteal artery.
      Subsequently a compartment syndrome, a false aneurysm of the popliteal artery and
      an arteriovenous fistula from popliteal artery into a lower leg vein developed.

PMID- 9199079
TI  - [Arthroscopic therapy of the unstable shoulder joint--acceptance and critical
      considerations].
AB  - PURPOSE: The purpose of this study was to document and to present the acceptance
      of arthroscopically performed stabilising procedures of the glenohumeral joint.
      METHOD: In a nationwide survey of instructors of the association of arthroscopy,
      members of the arthroscopy group of the german orthopedic society, and orthopedic
      and trauma surgeons with special interest in joint surgery we evaluated the
      current treatment modalities for patients with unstable shoulder joints. RESULTS:
      After an average of 2.09 +/- 1.0 shoulder redislocations surgery is recommended.
      The Bankart-operation (63.4%) is the favourite procedure for open surgery. In a
      descended order the Weber rotation-osteotomie, the Putti-Platt operation, the Max
      Lange procedure, and in a minimal amount of the cases the Bristow-procedure are
      performed. Looking at the arthroscopic procedures, the distribution is much more
      equal. The Caspari technique is used by 27.6% and the Morgan technique by 25.1%.
      Bone anchors are used by 20.4% and the Suretac is used by 18.9% of the surgeons.
      The anchor knot technique (8%) is only rarely performed. In case of an elongated
      capsule the majority of the surgeons would not perform arthroscopic surgery.
      42.4% of the surgeons judge the arthroscopic technique less secure. However,
      38.9% do not see any difference to open procedures. CONCLUSION: Taking the
      available information, arthroscopic stabilising procedures seems to have slightly
      inferior results compared to standard open surgery. The Bankart procedure with or
      without a capsular shift is still the golden standard.

PMID- 9199080
TI  - [Thoracic outlet syndrome--an interdisciplinary topic. Experience with diagnosis
      and therapy in a 15-year patient cohort (80 trans-axillary resections of the 1st
      rib in 67 patients) and a literature review].
AB  - Because of its wide variety of symptoms, the neurovascular compression syndrome
      of the upper thoracic aperture or thoracic outlet syndrome (TOS) has to be
      distinguished from several differential diagnoses, especially orthopedic ones. It
      is mainly characterized by pressure lesion of the brachial plexus and secondly,
      by accompanying vascular damages. An indication for surgery exists in cases of
      persisting or increasing complaints or function loss of shoulder, arm or hand
      muscles as well as in cases with occurrence of vascular damage. The treatment of
      choice consists of transaxillary resection of the first rib. This report presents
      a record of our results after transaxillary surgery and compares them to the
      results given in current international literature. During the last few years 3031
      cases of transaxillary resections (13-473 cases) were described in international
      literature. The average follow-up period was 7.8 years (2-22 years). The results
      were good in 81.4% (50-93%) of the cases. From 02/80 to 03/94, we treated 67
      patients with altogether 80 thoracic outlet syndromes (TOS). Each of them was
      treated similarly with extensive transaxillary resection of the first rib,
      excision of fibrous bands and, if necessary, of cervical ribs. Our results after
      surgery (84.5% of complete resolution or improvement of symptoms) compare
      favorably to those given by other authors. The average follow-up period was 6.6
      years (0.5-14 years). Our results confirm, that transaxillary resection of the
      first rib is the method of choice in the treatment of thoracic outlet syndromes.

PMID- 9199082
TI  - IXth Belgian Week of Gastroenterology. 1997. Abstracts.

PMID- 9199081
TI  - [Radiological determination of femoral rotation deformity--computerized
      tomography, optimized measurement accuracy and exposure dosage].
AB  - 58 Patients, suspicious to have rotation deformity of the femur, were examined.
      To compare the value of diagnostic methods in measuring the degree of malrotation
      we estimated this degree using clinical examination and calculated the
      anteversion of the femoral neck, taking radiographs in the technique of Dunn and
      Rippstein, and a modified method of computed tomography. Only in twelve cases the
      direction of malrotation was corresponding in all three methods, although
      considerable variations in quantitative results were noted. Maintaining the exact
      position of the patient, necessary to get reproducible results using conventional
      X-ray technique, was impossible in most cases of patients with posttraumatic
      joint-stiffness and malalignment. Determination of femoral neck anteversion using
      this modified method of CT is a quick, reproducible technique to calculate the
      degree of malrotation, insensitive to the position of the patient. By means of
      this CT method it was possible to approach the highest accuracy in precise
      preoperative planing. Furthermore the radiation exposure could be reduced in a
      range of 20%-40%.

PMID- 9199083
TI  - [Positional impedance tests with acetazolamide: a clinical test for evaluating
      endolymphatic hydrops].
AB  - The authors report on the possible advantages acetazolamide, in conjunction with
      Positional Impedenzometry, can provide in the detection of minor labyrinthine
      hydrops and major labyrinthine fluid tension disorders. This study was carried
      out using the case/control method. The subjects were selected on the basis of
      symptoms and clinical examination revealing signs of endolymphatic hydrops. Tonal
      audiometry and positional impedenzometry according to Marullo were performed both
      before (pre-test) and after i.v. administration of 500 mg sodium acetazolamide
      (post-ACZ1 and post-ACZ2). Audiometry showed that in 77.2% of the cases there was
      a significant variation in threshold. In positional impedenzometry the average
      post-ACZ1 (delta PISC went from 22.06% (pre-test) to 13.16% and the post-ACZ2
      (delta PISC went to 23.15%). On the other hand no significant changes were seen
      in the controls. Some hypotheses are offered on the mechanisms giving rise to
      these effects and particular attention is focused on the effect acetazolamide has
      on the carbon dioxide in the endolymphatic sac. In conclusion the authors
      consider the advantages this method offers over the "classical" tests used in
      diagnosing Meniere's Disease and minor hydrops.

PMID- 9199084
TI  - ["Silent" gastroesophageal reflux and upper airway pathologies in childhood].
AB  - In children, gastroesophageal reflux (GER) plays an important role in both acute
      and chronic upper airway disorders including stridor, chronic cough, recurrent
      upper respiratory infections, obstructive apnea, laryngospasm, and wheezing.
      Diagnosis may prove difficult unless there is reason to suspect GER and one is
      aware of the concept of "silent" GER. This paper presents our experience with
      chronic and/or recurrent respiratory disorders of uncertain origin and without
      gastrointestinal symptoms in children. Thirty-two pediatric patients with upper
      respiratory symptoms were evaluated. Out-patient 24-hour intraesophageal pH was
      monitored and 56% of the patients underwent pharyngo-laryngeal fibroscopy. The
      patients were divided into two subgroups: Group A (18 patients < 6 months of age)
      and Group B (14 patients > 6 months). All the patients tested positive for GER
      with a mean Reflux Index of 21.5. The most common symptoms in Group A were apnea
      cianosis and stridor while they were chronic cough for group B. The present study
      confirms the association between GER and respiratory disease and between GER
      respiratory-related symptoms and patient age. Emphasis is placed on the
      importance of otolaryngological diagnostic procedures and 24-hour pH
      gastroesophageal monitoring in evaluating patients with respiratory disorders
      related to silent GER.

PMID- 9199085
TI  - [An oropharyngeal-esophageal scintigraphic study of deglutition].
AB  - The aim of the present work was to evaluate whether oro-pharyngeal-esophageal
      scintigraphy could be used in the dynamic study of the various phases of
      deglutition and to determine whether it could be applied in
      otorhinolaryngological practice along with videofluoroscopy and videoendoscopy.
      The patients were divided into four different groups according to clinical
      features and the scintigraphic data were analyzed on this basis. Emphasis is
      placed on the ease of this technique, its tolerability and the low level of
      radiation. It is pointed out that scintigraphy is quite useful in determinating
      the exact percentage of the bolus inhaled into the trachealbronchial branch and
      in measuring the transit time of the various phases of deglutition in detail. In
      patients affected by upper airway-digestive tract neoplasms it is, therefore,
      possible to make a semiquantitative evaluation of the results of surgery.
      Moreover, with this method the results of any rehabilitation can be measured as
      well as the onset of compensation mechanisms.

PMID- 9199087
TI  - [Radical radiotherapy in T2N0 glottic laryngeal carcinomas].
AB  - The present work analyzes the clinical results obtained at the Istituto del Radio
      in Brescia, Italy, using radiotherapy in the treatment of T2N0 glottic
      carcinomas. The analysis covers a sampling of 127 patients who had been treated
      using fixed field with 60Co or linear accelerator (high energy photons) technique
      delivering a minimum target dose of 60 Gy over the course of a 6-week period; 200
      cGy a day. The purpose of the present study was to evaluate: treatment response 3
      months after treatment was suspended using the WHO nomenclature; Overall Survival
      Rate and Actuarial Disease-Free Survival Rate at five and ten years from the end
      of treatment comparing the results obtained in cases of T2a and T2b; biological
      cost of treatment in terms of late recurrences. Three months after treatment had
      ended, a complete response was seen in 95% of the patients. The overall survival
      was 85% at five years while the NED survival was 67% at five years. Surgical
      salvage made it possible to treat 44% of those who did not respond to
      radiotherapy or who had a recurrence. Late recurrence rate was 4.7%. The clinical
      results are slightly lower than those obtained in the literature for surgical
      series in terms of survival probability. They were, however, certainly better in
      terms of good vocal preservation.

PMID- 9199086
TI  - [Cytokeratin and vimentin expression in laryngeal squamous cell carcinoma].
AB  - The present study employed immunohistochemical methods to study the cytokeratin
      (ck) and vimentin expression in 40 cases of laryngeal squamous cell carcinoma.
      Specific monoclonal isoform antibodies and mixes of antibodies vs. a specific
      molecule were used in order to determine what cytokeratins were present as
      accurately as possible. In this sampling two ck patterns were identified based on
      whether the ck pair 8/18 was present or not. The ck 8/18 positive cases were
      further broken down into three sub-groups based on the expression of one of the
      following: the ck 4/13 pair, ck 1/10 pair or vimentin. A statistically
      significant relationship was found between these sub-groups, the site at which
      the neoplasm arose and the tendency toward regional metastases. Moreover, it was
      found that the presence of ck 13 in a squamous cell carcinoma is correlated with
      the less aggressive forms, as indicated in the literature.

PMID- 9199088
TI  - [Case report: pleomorphic adenoma of the lateral nasal wall].
AB  - Pleomorphic adenoma is a tumor which most often originates from one of the major
      salivary glands; it is rarely located in the lacrymal glands and it is highly
      exceptional in the nasal cavity. Cases of pleomorphic adenoma in the nasal cavity
      have been described by Spiro (40 cases), Compagno and Wong (40 cases) and Suzuki
      et al. (41 cases). This type of tumor generally originates from the septal mucosa
      even though the seromucosal glands are mostly located in the lateral nasal wall.
      This pathology is more frequently found in females. The clinical signs of this
      tumor are non specific, slow unilateral nasal occlusion, rhinorrhea and, at
      times, epistaxis. Evolution is generally local although locoregional and distant
      metastases have been described in the literature. This sort of tumor has no
      specific appearance and thus diagnosis is based on histology. Indeed,
      microscopically nasal pleomorphic adenoma differs from salivary gland adenoma for
      the predominance of the cellular component over the connective component. The
      epithelial cells are small, oval-shaped and often arranged in cordons; they are
      sometimes organized in small acinous structures. The connective component can be
      mixoid, condroid or collagenous; follicles with squamous metaplasia and mitosis
      are rare. Histologically differentiating this disorder from olfactory esthesione
      uroblastoma can prove difficult; the lack of extra cellular neurifibrillar
      structures, neurotubules and neurosecretory granules in nasal pleomorphic adenoma
      are the main distinguishing criteria. The present work reports a case of a 45
      year-old man who had suffered of an increasing unilateral nasal obstruction from
      1 year. Endoscopic examination showed a smooth surface neoplasm involving the
      entire nasal cavity. CT scan showed the deformation of the medial bone wall of
      the maxillary sinus and of the ethmoid although without any osteolysis. Median
      maxillectomy surgical exeresis of the neoplasm was performed with the facial
      degloving technique. Histology revealed a 5 cm pleomorphic adenoma originating
      from the lateral nasal wall. This origin is extremely rare because this tumor
      generally originates in the nasal septum. Immunohistochemical stains proved
      positive for epithelial membrane antigen (MNF 116), for myoepithelial cells
      (PS100) and for stromal cells (Vimentine) with the epithelial elements
      predominating. After 9 months of follow-up the patient is still disease free.

PMID- 9199089
TI  - [Wegener granulomatosis: a clinical case with parossistic positional vertigo due
      to involvement of the lateral semicircular canal].
AB  - The ear is involved in more than 20% of all cases of Wegener Granulomatosis
      (W.G.): such involvement takes place either through direct proliferation of the
      necrotic-granulomatosis tissue in the middle ear, or is a consequence of
      perieustachian tube infiltration from the rhinopharnyx. The inner ear is affected
      later and it is not clear as to exactly how. The present paper deals with the
      case of a 63-year-old woman who had a year been suffering from bilateral ear
      pain, and persistent otorrhea with typical signs of purulent chronic middle-ear
      otitis. During the course of the illness the patient complained of atypical
      paroxymal positional vertigo, compatible with cupulolithiasis of the semi
      circular horizontal canal (as per E.N.G. recording). Transoral biopsy of the
      rhinopharynx and of the left nasal fossa revealed histopathological signs
      compatible with W.G.. In the light of post-mortem temporal bone studies performed
      by Friemann and Blatt on W.G. patients the present case could lead to further
      studies regarding the advancement of this pathological process within the middle
      and inner ears and the etiopathogenetic mechanisms involved. In particular,
      during the course of W.G., the appearance of benign paroxymal positional vertigo
      through cupulolithiasis of the semicircular horizontal canal may be justified: a)
      by the progressive involvement of the posterior labyrinth structures affecting
      the semicircular canals prior to the lateral canal and running on to the
      posterior canal; b) by the discovery of proteiform material in the labyrinthine
      fluids.

PMID- 9199090
TI  - [Congenital intranasal cephalocele: diagnosis and treatment].
AB  - The term cephalocele indicates a rare congenital malformation in which
      intracranial contents are extended through a defect in the cranium and dura
      mater. Intranasal cephaloceles belong to the group of basal cephaloceles. They
      can easily be misdiagnosed as nasal polyps and this can be potentially fatal
      after erroneous polypectomy. Three cases of transethmoidal cephalocele are
      presented, each with intermittent cerebrospinal fluid (CSF) rhinorrhea. The
      presence of a positive 2-transferrin-band in the immunological tests performed on
      the nasal fluid proved particularly helpful in diagnosing CSF. Other clinical
      sings were nasal obstruction associated with a solid intranasal mass, recurrent
      sinusitis and extensive pneumocephalus associated with headache after forceful
      nose-blowing. In all cases CT-scan delineated the osseous defect in the anterior
      skull-base, although MRI proved superior in soft-tissue resolution and
      multiplanar scanning. In one case surgery was a frontal craniotomy combined with
      endonasal endoscopic ethmoidectomy while in the other two a transethmoid approach
      was used. The present report emphasizes the distinctive clinical features of
      congenital intranasal cephaloceles and indicates the diagnostic and surgical
      procedures.

PMID- 9199091
TI  - [Allergic fungal sinusitis: is this rare disease an allergy or infection?].
AB  - Allergic Fungal Sinusitis (AFS) is a newly recognized form of benign, non
      invasive sinusitis the histopathologic features of which are similar to those of
      allergic bronchopulmonary aspergillosis. AFS is a rare condition. However,
      because treatment and prognosis vary widely, it is important that this disorder
      be recognized and differentiated from chronic bacterial sinusitis and other forms
      of fungal sinusitis. AFS does not discriminate by age although it is primarily
      found in young adults. AFS patients are usually atopic, often having a history of
      asthma and nasal polyposis. Many have suffered from the symptoms of chronic
      sinusitis for years while others have had multiple sinus surgery. Radiographs
      reveal the involvement of multiple sinuses, often with bone destruction.
      Laboratory findings support an allergic state with a marked increase in
      eosinophilia and total IgE. At times RAST testing proves positive for fungi and
      immediate cutaneous reactivity to fungi is also present. Histologic review of the
      sinus contents reveals characteristic "allergic mucin", with numerous
      eosinophiles, Charcot-Leyden crystals and fungal hyphae, without any fungi tissue
      invasion. A wide variety of fungal agents has been implicated, although the
      majority belong the Dematiacee family. Those patients with allergic mucin but no
      documented fungi are indicated as having AFS-like syndrome. The pathogenesis of
      AFS is uncertain. There is controversy in the literature as to what role
      hypersensitivity (Gell and Coombs type I and type III responses) in infection
      play. To date current therapeutic recommendations include complete exenteration
      of all allergic mucin. Adjunctive, short-term systemic steroids often prove
      useful and nasal steroid spray should be continued for long term. Systemic
      antifungal agents are not recommended in AFS. Recurrence is common and thus close
      clinical, endoscopic and radiographic follow-up is important. The
      clinicopathologic features of one patient with AFS are reported and
      etiopathogenetic problems are discussed. The presented case showed a positive
      culture with negative immunological testing (RAST-positive and immediate
      cutaneous reactivity to fungal antigen), thus confirming the pathogenetic
      hypothesis of the saprophytic fungal growth in an atopic patient.

PMID- 9199092
TI  - [Laryngeal amyloidosis: a case report].
AB  - Laryngeal amyloidosis is a rare, benign disease of the larynx the histology and
      clinical progression are uncertain. The present work reports a personal case of
      systemic amyloidosis principally involving the larynx. After a brief review of
      the literature regarding the classification of amyloidosis, its pathology and
      clinical implications are updated; in addition the present treatment modalities,
      diagnostic elements and prognosis are taken into consideration. In particular,
      the paper views the importance of a multidisciplinary approach in dealing with
      all patients presenting an organ-limited form of this disease as well as the
      application and advantages of carbon dioxide laser during the course of
      endoscopic surgery.

PMID- 9199093
TI  - [The ancient therapy of scrofula: the royal touch].

PMID- 9199094
TI  - [Rendu-Osler disease. Letter].

PMID- 9199095
TI  - [Medical research. Letter].

PMID- 9199097
TI  - International workshop on nutritional attitudes and practices of primary care
      physicians. Heelsum, Netherlands, December 11-13, 1995. Proceedings.

PMID- 9199096
TI  - Re: The birth of CT.

PMID- 9199098
TI  - [Carotid chemodectoma].

PMID- 9199099
TI  - [Secretory middle ear otitis with severe sensorineural deafness].
AB  - Secretory middle ear otitis is of difficult assessment in children with severe
      hearing impairment. This otitis, very frequent in infants and children,
      influences negatively the auditive capacity and apprenticeship as well. Our study
      deals with the prevalence and severity of the secretive middle ear otitis in an
      scholar population handicapped by a heavy hypoacusia. Demographically, etiologic
      and seasonal correlations are considered in the paper. The outcome shows a high
      incidence of the condition, an inversely relation with the age, an evident
      seasonal distribution and the absence of correlation between etiology of middle
      ear disease and sensorineural deafness.

PMID- 9199100
TI  - [Verrucous carcinoma of the larynx. An analysis of 20 years of experience].
AB  - Retrospective study about 10 verrucous carcinomas of the larynx surgically
      treated in a 20-year-term. This variety accounted por the 1.9 percent of the
      cancers seen in that period of time. Tabagism and alcoholism predominated in 8
      and 6 patients respectively. Glottis was the localization and dysphony the
      paramount symptom. In the paper are emphasized the most important histologic
      features. Koilocytosis was present in 6 cases. Four patients developed a second
      tumor of epidermoid carcinoma type. No one exitus due to the verrucous growth.
      Only in 3 the death was attributed to the second malignancy.

PMID- 9199101
TI  - [Granular cell tumor of the larynx].
AB  - Granular cell tumor is an unusual growth of probably neuroectodermal
      histogenesis, first reported by Abrikossoff in 1926 with the name of myoblastoma.
      Of the about 1200 cases reported since, the 50 percent were found in the head and
      neck. Of second mentioned 10 percent had a laryngeal sitting. A case of glottic
      granular cell tumor surgically removed with free borders is presented.
      Bibliographical review.

PMID- 9199102
TI  - [The importance of psychological profile of patients with tinnitus].
AB  - We performed a psychological profile study in 43 patients showing tinnitus as
      only symptom. We have employed two different questionnaires, EPI and STAI, to
      evaluate the state of neuroticism, extroversion and anxiety. The score of
      neuroticism and anxiety are very important in order to get and individual
      treatment.

PMID- 9199103
TI  - [New advances in inner ear diagnostic imaging].
AB  - Recent applications of magnetic resonance in the ear pathology are described.
      Attention is drawn to the new magnetic resonance sequences in two and three
      dimensions and their contribution to the understanding of anatomy and pathology
      of the inner ear, especially the membranous labyrinth.

PMID- 9199104
TI  - [An increase of plasma cells in the regenerated mucous membrane of maxillary
      sinus. Experimental study].
AB  - In ten albino New Zealand rabbits we studied in the regenerated mucosa of the
      maxillary sinus what happens after three months of radical removal of sinus
      mucosa. The study was realized by light and electronic microscopy, with special
      attention to the plasma cells around the submucosal glands. There is an increased
      of plasma cells, in a proportion of 10:1.

PMID- 9199105
TI  - [Labyrinthine complications of chronic cholesteatoma in middle ear otitis].
AB  - Account clinic and therapeutic of one case, seen and treated by the A., of
      labyrinthine complication (labyrinthine fistula) secondary from an otic
      cholesteatoma encroaching the mastoid process. Its medicosurgical importance is
      emphasized.

PMID- 9199106
TI  - [Anxiety and vertigo].
AB  - AIM OF THE STUDY: To determinate the prevalence of anxiety associated with
      vertigo of vestibular origin. DESIGN: A retrospective study. SETTING: Patients
      from Salamanca's University Hospital (Neuro-Otology). PATIENTS: 138 patients with
      asymptomatic vestibular dysfunction (group A: with filiated disease and group B:
      with unfiliated disease). INSTRUMENTATION: Structured anamnese and STAI
      questionnary (State-Trait-Anxiety-Scale) were realized in the whole collective.
      RESULTS: Anxiety (elevated score in STAI-scale) was detected in 48.6% patients
      and more differences between groups A and B were not significant. With logistic
      regression anxiety is related with previous symptomatological experiences and
      subjective global incapacity. Anxiety is clearly connected with the symptoms in
      the intercritic periods. CONCLUSION: Anxiety is associated with vestibular
      disease and it follows a parallel course.

PMID- 9199107
TI  - [Magnetic resonance and metastatic neck adenopathies. Usefulness of the technique
      for cervical staging].
AB  - 25 patients with epidermoid carcinoma of the larynx underwent staging of cervical
      adenopathies by magnetic resonance imaging (MRI). All patients subsequently
      underwent neck dissection. The MRI results were compared with the
      histopathological findings ans those gained through previous palpation. MRI
      correctly staged 54.1% of patients with a sensitivity of 66% and a specificity of
      74%.

PMID- 9199108
TI  - [Hypoacusis and diabetes type II].
AB  - The relation between diabetes mellitus and hypoacusis is discussed since Jordao,
      who firstly pointed out to this association in 1854. The disparity of results
      according several studies are due, after other AA., to the heterogeneous of
      groups considered. Our study was done resorting to a patients selection and their
      classification in 2 homogeneous groups following different parameters: age; sex;
      years of course; verified angiopathic complications: peripheric vasculopathy,
      microalbuminuria, altered creatinine clearance; malady control: glycosylated
      hemoglobin. The task consisted in the study of audiometric tracings in 40
      patients in order to verify statistic differences of auditive thresholds between
      the established groups. These courses corresponding to a sensorineural hearing
      loss with a deep in high tones. But no significatively worse thresholds in
      patients suffering other angiopathic disorders were detected.

PMID- 9199109
TI  - [Vernet's syndrome as an early manifestation of systemic erythematous lupus].
AB  - Report of one case of Vernet's syndrome (involving the IX, X and XIth cranial
      nerves) in a young woman, as early sing of SEL. The patient presented the 4
      criteria suggested by the American Society in order to diagnose SEL: arthritis,
      serositis, positive anti-nuclear antibodies and anemia. The AA. carry out a study
      in search of other cases sitting in the larynx and a perusal about
      etiopathogenical theories as well. Hinting, for the clinical picture, of being it
      due to a localised vasculitis of vasa nervorum, a treatment with corticoids and
      pentoxifylline was ordered, being the outcome, after 3 weeks, the eradication of
      ENT syndrome.

PMID- 9199110
TI  - [A rare case of angiolymphoid intramasseteric hyperplasia].
AB  - A white caucasian male 38-year-old has come to our Department with an
      intramasseterin neoformation. The histopathological report has been angiolymphoid
      hyperplasia. Surgical approach is discussed considering at the same time the
      peculiarity of this rare type of intervention.

PMID- 9199111
TI  - [Endoscopic surgery of turbinates and nasal obstruction].
AB  - Nasal blockage is one of the most habitual symptoms in otolaryngologist office
      and the concha nasalis inferior hypertrophy the commonest cause of the trouble.
      Cases in which medical treatment is refractory, surgery could be an optional
      resort in accordance of a great deal of specialists. The possibility of give rise
      to atrophic rhinitis or even ozenatous lesions has been refraining this surgery
      lately. In our series are contemplated the outcomes of several surgical
      procedures as mode of management of the hypertrophy of the lower turbinal. In the
      article are assessed the results of several surgical techniques dealing with
      hypertrophy of concha nasalis inferior. 75 patients were operated under
      endoscopic control. Some underwent a submucous decompression (SD) other partial
      resection (PR). Results at half and long term of both techniques-the conservative
      one (SD) and that a little more aggressive (PR)-are compared, and so are the
      factors conditioning the selection of the surgical procedure done. We consider
      the partial resection of the inferior concha, under endoscopic vision, as the
      best way for improving the nose obstruction due to inferior concha hypertrophy,
      provided conservative measures are not wise at all. Furthermore because with our
      own hands we reach very good outcomes, both in breathing and nasal comfort. Only
      the patient's age may influence the last decision.

PMID- 9199112
TI  - [Infantile capillary hemangioma of the outer ala nasi. Report of a case].
AB  - We report a case of inferior turbinate capilar hemangioma in a 12-year-old
      patient. Clinical and radiological findings are commented and the limited
      literature up to the present is reviewed. We think that the present publication
      is opportune because of the patient's age and the nature and origin of the mass.
      Surgery appears to be the elective treatment in most cases.

PMID- 9199113
TI  - [Morphological and morphometric study of sphenoidal sinus].
AB  - Thanks to the help of anatomical dissections and imaging techniques we way
      present this paper in which are described the morphologic characteristics of the
      sinus, its pneumatization types more frequently encountered, the traits more
      noteworthy related to the intersinusal partition and bone crests inside the sinus
      as well the distances detaching the sinus from the anterior wall of the sella
      turcica and clivus, through which wall the sinus cavity keeps in touch with noble
      cranial structures as the hypophysis and the brain stem. Ultimately our outcomes
      are compared with those given by other researchers.

PMID- 9199114
TI  - [Chronological development of the sphenoidal sinus].
AB  - In this paper are exposed the main characteristics of the sphenoidal sinus rise,
      through a follow-up of its growth during the life-span of the first 20 years of
      life. For so doing the AA. studied the antero-posterior diameters, the vertical
      greatest diameter and the several distances detaching this sinus from other
      important anatomical references, as well the various degrees of pneumatization
      that the cavity may reach according as the years go over.

PMID- 9199115
TI  - [Release of the septum in endoscopic nasosinusal surgery].
AB  - Systematical partial liberation of the septal cartilage through limited resection
      of the perpendicular plate of the ethmoid and/or vomer, as prior of endoscopic
      nasosinusal surgery, eases the exposure and approach to the whole sinusal
      complex, especially to maxillary sinus, so facilitating and shortening the length
      of the procedure. Furthermore facilitates the entrance inside the surgical cavity
      during cures, also decreases the patient's nuisances and hinder the occurrence of
      some complications, as postoperative synechiae.

PMID- 9199116
TI  - [Treatment results and prognostic significance of selected clinical and
      laboratory features in children diagnosed with malignant lymphoma].
AB  - The clinical picture and results of treating malignant lymphoma in children,
      diagnosed and treated at the Pediatric Institute of Pomeranian Medical Academy in
      Szczecin during the period between May 1979 and February 1992, were analyzed. The
      studied group consisted of 33 children (23 boys, 10 girls) aged between 41-169
      months (median 112 months, mean 110 months) having Hodgkin's lymphoma (HL), and
      35 children (26 boys, 9 girls), aged between 35-171 months (median 101 months,
      mean 104 months), with non-Hodgkin's lymphoma (NHL). Till 1987 the children with
      HL were treated according to MOPP program, and since 1988 with MVPP/B-DOPA. Two
      children were treated according to COMP and ABVD programs. The NHL children were
      treated till 1985 with LSA2L2 or COAMP, and from 1986 with BFM-NHL 86 with the
      modification of methotrexate doses. The duration of observation involving HL
      cases ranged from 2 to 156 months (median 76, mean 78 months), that covering NHL
      cases from 3 to 153 months (median 28 months, mean 44 months). It was proved that
      the results of HL treatment in the Pediatric Institute of Pomeranian Medical
      Academy in Szczecin were comparable with the results of other centers. The
      probability of event free survival (EFS) for the whole group was 0.818, for
      children treated by MOPP program was 0.888, for children with MVPP/B-DOPA was
      0.900. Unfortunately, the results of NHL treatment in our center in Szczecin are
      worse than those of other hematologic-oncologic institutions. The EFS was 0.550.
      The reason why our results were poor in treating NHL in our center was: delay in
      beginning the remission-inducing treatment because of diagnostic difficulties
      (especially in smaller hospitals): prolongation of the first remission-inducing
      therapy over 14 days, mainly due to generalized infection, generalized diathesis
      haemorrhagica with bleeding from the alimentary tract, and finally the need of
      modifying the treatment program BFM 86 concerning primarily the lowering of
      methotrexate doses from 5 g/m2 to 0.5 g/m2. That was necessary in view of our
      inability of monitoring the level of methotrexate in blood. All of those findings
      suggest the necessity of: 1) earlier proper diagnosis; the physicians taking care
      of children should be aware of high incidence of such neoplasms in children,
      especially with atypical clinical presentation; 2) full realization of the
      therapeutic program (particularly remission-inducing one). A general real
      improvement of the treatment conditions in hospitals is indispensable. The actual
      work has proved that in HL the detrimental prognostic factors included; the age
      above 10 years and histological type of nodular sclerosis. Children older than 10
      years had lower EFS (1.0 vs 0.65; p < 0.05). EFS in histological type of nodular
      sclerosis was also lower namely (0.925 vs 0.600; p < 0.05). In the NHL group the
      bad prognostic factors were the age over 10 years and proliferation of T-cells.
      Patients older than 10 years displayed statistically lower EFS (0.709 vs 0.288; p
      < 0.05). The children with T-NHL had also lower EFS (0.621 vs 0.187; p < 0.05).
      It is necessary that the prognosis in these children should be substantially
      improved by elaborating treatment programme being adjusted to cope with the risk
      factors.

PMID- 9199117
TI  - [Selected components of the kallikrein-kinin system and of the renin-angiotensin
      aldosterone system in offspring of parents with hypertension].
AB  - Essential hypertension is a very common disease in the world. Although the
      various systemic, local, genetic and environmental factors are known to be
      involved in its pathogenesis, others remain obscure. In offspring of hypertensive
      parents many biochemical abnormalities have been found distinguishing these
      persons from subjects without family history of hypertension. Recently, the
      correlation between a positive family history of hypertension and urinary
      kallikrein excretion has been reported. OBJECTIVE: 1. To determine selected
      components of the kallikrein-kinin system and renin-angiotensin system in
      normotensive offspring of hypertensive parents and in normotensive offspring of
      normotensive parents as control group. 2. To determine abnormalities of
      biochemical indicators known as the predictors of hypertension in offspring of
      hypertensive parents. The study was performed on 85 normotensive young slim (body
      mass index < 25) adults. They were subdivided into 4 groups: 21 subjects with no
      family history of hypertension as controls, 23 offspring of hypertensive mothers,
      27 offspring of hypertensive fathers, and 14 offspring of both hypertensive
      parents. After medical history, physical examination and routine biochemistry,
      the following parameters have been measured: plasma renin activity and
      aldosterone concentration in basic conditions, and after 40 mg furosemide i.v.,
      plasma angiotensin 1 converting enzyme activity, plasma prekallikrein level, Na/K
      ATPase activity and 24-hours urinary excretion of renal kallikrein, sodium,
      potassium and chloride. Tables 1-5. RESULTS: 1. No significant differences
      concerning the body mass index, plasma prekallikrein level, plasma renin activity
      and aldosterone concentration in basic conditions, and after 40 mg furosemide
      i.v., urinary sodium, potassium and chloride were found between controls and
      subjects with family history of hypertension as well as between controls and
      offspring of hypertensive mothers, fathers and both hypertensive parents. 2. The
      diastolic and mean arterial pressure in children of both hypertensive parents was
      in high normal range, but was significantly higher as compared to controls. 3.
      Compared to the control group, urinary kallikrein excretion was significantly
      lower in subjects with family history of hypertension, especially in offspring of
      both hypertensive parents. CONCLUSIONS: 1. The significant decrease of urinary
      kallikrein excretion distinguished the subjects with the family history of
      hypertension, especially offspring of both hypertensive parents. Low kallikrein
      excretion is often associated with diastolic blood pressure in high normal range.
      2. The co-existence of low kallikrein excretion and high normal diastolic blood
      pressure may be useful in predicting the higher risk for arterial hypertension to
      develop. 3. In offspring of hypertensive parents the impairment of kallikrein
      kinin system refers mainly to the tissue component. No changes have been found in
      plasma component of this system.

PMID- 9199118
TI  - [The influence of chronic exposure to carbon disulfide on metabolism of
      catecholamines and serotonin in women].
AB  - Due to more frequent occurrence of the idiopathic arterial hypertension of
      borderline type (18.97% of screened women), with values varying from 18.7/12.0 to
      21.3/12.7 kPa (140/90-160/95 mm Hg), in women chronically exposed to carbon
      disulfide as compared to the control group (8.5% women), we decided to
      investigate the activity of sympathetic-adrenal nad serotoninergic systems that
      play an important role in the haemostasis of cardiovascular system. The aim of
      the presented study is to evaluate the linear correlation between: 1) serum
      dopamine-beta hydroxylase activity and the dopamine concentration in plasma as
      well as 24-hours adrenaline and noradrenaline excretion in the urine; and 2)
      between catechol-0-methyltransferase and monoaminoxidase activity and the 24
      hours excretion of catecholamine in the urine; next the serum and platelet
      concentration of serotonin and the arterial blood pressure in women chronically
      exposed to carbon disulfide. The investigations were performed on 140 women, aged
      22 to 55, who were divided into two groups: group-I the control group, covered 50
      women employed in the Industrial Clothing Factory "Dana" in Szczecin. Group II
      the study group, consisted of women employed in the Synthetic Fibres Factory
      "Wiskord" in Szczecin-Zydowce, in the carbon disulfide (CS2) atmosphere in
      concentration from 9.36 to 23.4 mg/m3. The microclimate conditions of the
      production halls in both groups were similar (Tab. 1). It has been observed that
      in women chronically exposed to CS2 plasma dopamine concentration (p < 0.001) and
      DBH serum activity (p < 0.001) are significantly lower as compared to the control
      group parameters (Tab. 2). Also dopamine concentration and DBH activity are lower
      in all subgroups of women exposed to CS2 (Tab. 3). In women working in the CS2
      atmosphere, 24-hours excretion of adrenaline is significantly lower (p < 0.001)
      as compared to the control group. Parameters for 24-hours noradrenaline and VMA
      excretion in the urine do not show any statistical significance (Tab. 4). Plasma
      (p < 0.001) and platelet (p < 0.001) concentration of serotonin is significantly
      higher in women exposed to CS2. However, 24-hours 5-HIAA excretion in the urine
      in women of group II is higher than in group I, but does not give evidence of any
      statistical significance (Tab. 6). Both serum (p < 0.001) and platelet (p <
      0.001) MAO activity is significantly lower in women chronically exposed to CS2.
      Also COMT erythrocyte activity is significantly lower (p < 0.001) in the studied
      group women (Tab. 8). The women working in the CS2 evaporation display
      significantly higher serum concentration of total (p < 0.001), bound (p < 0.001)
      and free (p < 0.001) tryptophane (Tab. 9). In women exposed to CS2, serum
      concentration of zinc (p < 0.001) and copper ions (p < 0.001) is significantly
      lower (Tab. 10). In comparison to the control group parameters, the women exposed
      to CS2 claim values of systolic and diastolic arterial blood pressure being
      insignificantly higher. However, in women working in CS2 atmosphere the
      coefficients of linear correlation between plasma (r = 0.59; p < 0.001) and
      platelet (r = 0.73; p < 0.001) serotonin concentration and the systolic arterial
      blood pressure, as well as plasma (r = 0.065; p < 0.001) and platelet (r = 0.72;
      p < 0.001) serotonin concentration and the diastolic arterial blood pressure are
      significantly higher (Tab. 11). Significantly positive linear correlation between
      serotonin concentration and arterial blood pressure in women chronically exposed
      to CS2 may suggest the important role of this amine in the pathogenesis of
      arterial hypertension.

PMID- 9199119
TI  - [An attempt to evaluate prognosis in cases of metastasis from laryngeal and
      hypopharyngeal carcinoma to cervical lymph nodes].
AB  - The objective of the paper was the retrospective evaluation of oncological
      results after dissection radical (RND), modified (MND) and selective (SND) on
      cervical lymph nodes in laryngeal and hypopharyngeal carcinoma. On the basis of
      obtained study results, an answer was sought whether and what prognostic factors
      in metastases to the regional cervical lymph nodes should influence the choice of
      therapeutic method, and the survival. The study material comprised 986 patients
      treated during the period 1970-1991 in the Department of Otolaryngology-PAM in
      Szczecin due to laryngeal and hypopharyngeal carcinoma. In this group, apart from
      treating the primary changes, the cervical lymph nodes were operated on (Neck
      Dissection-ND). Data concerning the patients were obtained from: a/ case
      histories, b/ follow-up, c/ correspondence, d/ USC data. Clinical status of
      cervical lymph nodes, their histopathological state were assessed
      postoperatively. The patients' survival period after the treatment of carcinoma
      was estimated too. The occurrence of neoplastic disease recurrence in cervical
      lymph nodes was also taken into consideration. All data were collected in
      Personal Computer memory IBC (PC 386). In processing the data use was made of
      calculating and data base program Medikus. A linear regression model was
      elaborated for investigating the degree to which certain factors influence the
      appearance of nodal recurrence. Hierarchy was established for the factors whose
      influence on the occurrence of recurrence was the strongest. It becomes apparent
      from the accomplished studies that metastases to the regional cervical lymph
      nodes occurred most frequently in hypopharyngeal cancers (81.6%). The clinical
      assessment is burdened with an error claiming 31% of discrepancy as compared to
      results of histopathological examination (Tab. 3). Occult metastases were
      recorded in hypopharyngeal carcinoma about 20%, and in glottic one about 13%. It
      was revealed that the presence of metastases in lymph nodes, an increase
      affecting the stage of pT and pN reduced the chances of survival in a significant
      manner (Tab. 7 and 8). The greatest influence on the appearance of nodal
      recurrence was exerted by the following factors: number of metastatic nodes, size
      of nodes, component N, mode of treatment. It has been disclosed that the risk of
      nodal recurrence increases sixfold with the rise of factor N, twofold with the
      rise of the number of metastatic nodes, and 1,6 fold when the size of nodes
      increases by 1 cm. No differences were observed in the percentages of survivals
      following the operative treatment RND and MND, with the stage being N1-2 (Fig.
      1). Radiotherapy applied after MND and RND failed to exert any meaningful
      positive influence on the overall percentage of survivals (Tab. 4). As compared
      with therapeutic dissection, better oncological results, scored after
      prophylactic removal of cervical lymphatic system, provide the basis for elective
      performance of prophylactic procedures in hypopharyngeal and laryngeal
      carcinomata.

PMID- 9199120
TI  - [Evaluation of results from radiotherapy and combined treatment of laryngeal
      cancer (surgery and radiotherapy) considering differentiation of procedures with
      respect to lymph nodes in the neck].
AB  - The aim of the work was to estimate the therapeutic results in patients with
      laryngeal cancer treated by combined method (surgery and radiotherapy) and
      radiotherapy alone. In the group of patients treated by combined method the
      randomised clinical study, concerning regional lymph nodes arrangement, has been
      performed (Tab. 5). The control group of patients was treated, as before, by
      radical neck dissection (RND), or modified neck dissection (MND), or regional
      modified neck dissection (RMND), depending on the advancement of the tumor and
      lymph nodes involvement, combined with moderate postoperative dose of irradiation
      (5000-5500 cGy). Adversely, the study group was subjected to more conservative
      surgery, namely MND, or RMND, or LAC (lymphadenectomy) combined with
      postoperative, slightly higher, dose of irradiation (5500-6000 cGy) (Tab. 6).
      Clinical material of 213 patients, treated between 1986-1990 at the Laryngology
      Department and Radiotherapy Department of Pomeranian Medical Academy, has been
      analysed. There were 84 patients in the study group, 68 in the control group, and
      61 in exclusively irradiated group. The patients treated only surgically as well
      as those irradiated palliatively were excluded. The best results of treatment
      have been obtained in the study group (3-year survival 78%, and 5-year survival
      69%), worse in the control group (3-year survival 62%, and 5-year survival 51%)
      and the worst in the exclusively irradiated group (3-year 51%, and 5-year 44%)
      (Fig. 4). The most frequent cause of failure was local and loco regional relapse.
      The acute and late radiation morbidity, according to RTOG/EORTC classification,
      has been also analysed. In the majority of patients only slight and moderate (1
      and 2 grade), in some patients 3 grade, and in 2 patients 4 grade morbidity has
      been observed.

PMID- 9199121
TI  - [Optimization of dose distribution in combined irradiation of uterine cervix
      cancer with gamma-ray cesium-137 and X-9 MeV].
AB  - This study concerns the optimization of the dose distribution in all variants of
      combined irradiation of uterine cervix cancer which are used in our Clinic (Tab.
      1). The analysis of the doses of radiation in reference points as well as isodose
      distribution in the whole irradiated area has been done. All variants of combined
      irradiation and the localization of applicators in the intracavitary irradiation
      and field's arrangement of external beam irradiation have been shown. The second
      part of the study analyzes the physical parameters in conventional intracavitary
      irradiation by modified Manchester method in comparison with the Selectron-LDR
      (Tab. 5). The dose distribution around the applicators has been compared too. The
      biological equivalence of the doses in application of different dose rate sources
      has been estimated according to the principles of LQ-model (Tab. 3, 4). Relations
      between the reference point doses and such parameters as the length of
      intrauterine sond (Fig. 2), the size of applied ovoids (Fig. 3), the distance
      between them (Fig. 5) and the treatment sources' positions in the ovoids (Fig. 4)
      have been calculated. The dose distribution in all variants of combined
      irradiation of uteri cervix cancer has been demonstrated (Fig. 6). Total absorbed
      dose in the point A, as well as in the reference points of bladder, rectum and
      para-aortic, external iliac and common iliac lymph nodes have been calculated
      (Tab. 5). The position of regional lymph nodes was defined with the use of
      lymphography, two orthogonal radiograms and CT. In the last part of the work,
      after optimization of physical irradiation parameters and their biological
      equivalents, the dose distribution in all variants of combined irradiation has
      been calculated (Fig. 7). CONCLUSIONS: 1. The LQ-model allows to calculate the
      biological equivalent of total physical dose in combined irradiation when
      intracavitary irradiation is realised with different dose rate sources, and
      external beam therapy with different doses per fraction. 2. The use of the
      smallest ovoids in intracavitary irradiation leads to increased dose in the
      bladder and rectum. The use of small ovoids increases the dose only in the
      bladder in comparison to utilisation of medium and large ovoids. In such cases
      individual treatment planning is necessary. 3. The external iliac nodes are
      located above the points defined in the Fletcher lymphatic trapezoid. Therefore
      the lateral fields of pelvis lymph nodes irradiation should be at least 10 cm
      wide. 4. Depending on clinical advancement of uterine cervix cancer the
      optimisation of combined irradiation allows to obtain the desired dose in the
      target volume as well as in regional lymph nodes in each variant of irradiation.

PMID- 9199122
TI  - [Evaluating the efficacy of selected programs for prophylaxis of caries and
      periodontal diseases in school children with special reference to guidelines for
      oral cavity hygiene].
AB  - Endeavouring to improve the oral cavity soundness in 7-8 year-old children, an
      attempt was made to elaborate three prophylactic-educational programs with the
      possibility to apply them in school conditions. The aim of the work was to
      evaluate the efficacy of the said programs in the field of oral cavity hygiene,
      the status of periodontium and dental caries, as well as to observe the moulding
      of consciousness and correct hygiene habits. The clinical and questionnaire
      studies covered 255 pupils of two elementary schools in Szczecin. For the first 2
      3 years of their lives the majority of children used tap water having been
      fluoridated to optimal level. The pupils of both schools were receiving planned
      stomatological treatment and contact fluoridation. The clinical evaluation was
      accomplished on the basis of 18-month-long observation of the increase in the
      number of teeth and dental surface with caries (DMFt and DMFs), status of
      periodontium (ind. GI) and state of hygiene (ind. OHI-S and QH). The tooth
      brushing method applied by children was additionally observed. The questionnaire
      studies were employed for estimating the changes in the health consciousness and
      hygienic habits. The three selected programs were implemented in three groups of
      studied children (Tab. 1). Program I was based on II individual, motivating
      instructions of tooth brushing. The main motivating factor was each time
      colouring of the bacterial plaque. Programs II and III were expanded by
      educational activity among children and parents. Program III was additionally
      enriched by professional cleaning of teeth, sealing and intensive conservative
      treatment. The above programs were carried out in cooperation of school
      stomatologist, teachers and V year stomatology students and girl pupils training
      for hygienists. The high frequency and intensity, hardly fair hygiene of the oral
      cavity and improper habits, having been disclosed in 7-year-old children during
      preliminary examinations, indicated that there was an urgent need to intensify
      the educational-prophylactic-therapeutic procedures. After 18-month-long studies
      it appeared that program I was effective with regard to improving hygiene
      (reduction of ind. QH by about 13%) (Fig. 1) and the status of gums (reduction of
      ind. GI by about 54%) (Fig. 2), however, it failed to exert any effective
      influence on the reduction of caries. Programs II and III were found to be
      effective with respect to the improvement of hygiene (reduction of ind. QH about
      18 and 20%) (Fig. 1), status of gums (reduction of ind. GI about 67 and 67%)
      (Fig. 2) as well as reduction of caries (about 68 and 56%). Thus, for the
      exploitation under school conditions each of the three evaluated programs may be
      engaged, but the most recommendable would be program II or III. The actual
      studies have also shown the possibility of obtaining a distinct improvement in
      hygiene in a short time, however, a longer period of time was necessary to
      stabilize it. Moreover, the process of introducing a correct method of brushing
      the teeth appeared to be relatively difficult, but it was much easier to achieve
      that in the children who up to now have made use of partly correct method than in
      those who used an incorrect one. The implementation of the selected programs had
      stronger influence on the correction of health consciousness and weaker on the
      moulding of the habits of brushing the teeth with appropriate frequency. Reverse
      proportional dependence was also revealed to exist between caries intensity in
      children studied and the education of their parents.

PMID- 9199124
TI  - [Bibliography of publications of scientific workers from the Pomeranian Medical
      Academy for the year 1994].

PMID- 9199123
TI  - [Concentration and distribution of fluorine in hen's eggs as an aspect of
      selected biological parameters].
AB  - The actual paper presents the method and results of studies concerning the
      content and decomposition of fluorine compounds in the component structures of
      eggs and in the bone system of a domestic hen, as well as its progeny under
      conditions of increased content of these compounds in the drinking water. The
      objective of the paper has been: 1) determining the effect of environmental
      contamination (NaF in drinking water) exerted on the presence of fluorine in
      eggs, 2) defining the distribution of fluorine in component structures of the
      egg, 3) studying the fluorine effect on selected physical parameters of eggs, 4)
      determination of fluorine content in tibial bones of laying hens, after receiving
      NaF in drinking water, and to compare the tibial bone composition in hens and
      their progeny with control groups, 5) analyzing the share of fluorine compounds
      in the construction of skeleton and beaks of chicks. The conceptions of the work
      were elaborated on the basis of results stemming from an accomplished
      experimental breeding of domestic hens in a semi-intensive system. The experiment
      proceeded 4 weeks. A part of eggs obtained by breeding was designed for hatching.
      Due to the requirements associated with analyzing the skeleton, all the
      experimental birds, including the chicks, were assigned for further analyses. The
      material, obtained in this way, (bones of hens, chicks, eggs) was subsequently
      subjected to detailed studies. According to the conceptions of the paper the
      selected physical parameters of eggs were studied, therein resistance tests,
      using specialized apparatuses. Fluoride was determined potentiometrically, by
      applying fluoride ion selective electrode, while the metallic elements by aid of
      atomic spectrophotometer (Tab. 1-5, Fig. 1). Finally, the following conclusions
      were presented, namely: 1. The egg shell in hens plays an essential role in
      binding fluorine compounds and constitutes one of the means of their fast
      elimination from the organism. 2. Egg shells may provide an easily accessible
      bioindicator for the exposure of birds to fluorine compound, particularly with
      regard to a given species. 3. Moderately increased fluorine content in the shells
      of eggs fails to influence their thickness and does not cause any changes in
      their resistance to decay. 4. In conditions of increased exposure of hens to
      fluorine compounds, no elevation in the accumulation of this element was
      disclosed in the substance, which is evidence that there is a lack of apparent
      influence of local contamination by emissions of fluorine compounds exerted on
      nutritional usefulness of eggs. 5. Comparison of fluorine content in the bones of
      chicks, stemming from hens being given water with NaF to drink, with control hens
      points to a significant rise in fluoride accumulation in progeny of hens, exposed
      to sodium fluoride action. That may have a negative influence on their correct
      development.

PMID- 9199125
TI  - [Comparative pharmacokinetics of theophylline in hyperlipidemia in animals and
      humans].
AB  - The incidence of hereditary hyperlipidemia amounts to about 8% and rises when
      secondary causes of lipid metabolism disturbances are taken into consideration.
      In contemporary literature there is paucity of data on the influence of
      hyperlipidemia on pharmacokinetics of drugs. That is especially important in the
      case of drugs characterized by a narrow therapeutic index, such as theophylline,
      which can be administered to patients affected by an altered lipid status. The
      investigation was aimed at evaluating the feasibility of an animal model of
      hyperlipidemia for pharmacokinetic studies of theophylline in humans suffering
      from lipid metabolism disturbances. The study was carried out on male rabbits
      divided into two groups: a control and an experimental one, fed on a high-fat
      diet. Humans were also ascribed to two groups: controls and those affected by
      primary, mixed-form of hyperlipidemia. The animals were given theophylline
      intravenously in a single dose of 12 mg/kg, whereas humans received intravenously
      injected theophylline in a single dose of 3.5 mg/kg. Blood was sampled after 5,
      10, 15, 30, 45 minutes and 1, 2, 4, 6, 8, 12, 24 hours following theophylline
      administration. FPIA method was used to determine blood serum concentrations of
      theophylline (Tab. 1,3). The two-compartment open model for intravenous
      administration was applied for calculations. Considerable alterations of
      theophylline pharmacokinetics in humans suffering from mixed form of
      hyperlipidemia were observed (Tab. 4), whereas no marked changes were noted in
      animals with alimentary-induced hyperlipidemia (Tab. 2). In hyperlipidemic
      rabbits theophylline behaves as lipophilic agent, despite its poor penetration
      into the adipose tissue. A considerable decrease in area under the concentration
      time curve of theophylline, increase in transfer constants as well as accelerated
      elimination of the drug were observed in humans with mixed form of
      hyperlipidemia. The behaviour of theophylline in hyperlipidemic rabbits was
      different from that in patients with mixed form of hyperlipidemia. Comparison of
      theophylline pharmacokinetics in hyperlipidemic animals and in human subjects
      revealed that an animal model of hyperlipidemia was inappropriate for studying
      the effect of lipid metabolism disturbances on pharmacokinetics of drugs as it is
      shown in the study on theophylline. This can be explained, to some extent, by
      different mechanisms of hyperlipidemia in rabbits and in humans. Hyperlipidemia
      in rabbits was induced by alimentary factors, while in humans lipid metabolism
      disturbances were of primary origin. Basing on the results of the present study
      it may be suggested that there are no general rules for anticipating the
      influence of hyperlipidemia on the pharmacokinetics of drugs in various
      organisms. Therefore, it is most likely that studies on the influence of
      hyperlipidemia on the pharmacokinetics of drugs should be performed for every
      particular drug separately.

PMID- 9199126
TI  - [The effect of experimental extrahepatic cholestasis on absorption, distribution
      and elimination of digoxin].
AB  - Clinical observations indicate an increased number of post-operative
      complications and deaths in jaundiced patients. The patient may require some
      simultaneous treatment of concomitant ailments, among which cardiovascular
      diseases occur rather frequently. Some of the drugs administered then, like
      digoxin, are, in spite of being predominantly eliminated via the kidneys,
      metabolized in the liver, secreted into the bile or participating in the
      enterohepatic circulation. The changed pharmacokinetics of such drugs, in the
      case of mechanical jaundice, may be due to an altered liver status which can
      affect the function of the kidneys. The aim of the study was to evaluate the
      pharmacokinetics of digoxin administered both intravenously and into the stomach,
      in the state of mechanical, extrahepatic cholestasis. The study was carried out
      on male rabbits, divided randomly into four groups: the first two (experimental
      and control) were administered digoxin intragastrically and the next two groups
      (experimental and control)-intravenously (Tab. 1). The animals of the
      experimental groups had the bile ducts ligated, whereas the controls were sham
      operated on. Digoxin was given to all the animals 4 days before the operation and
      6 days after the surgery, in a dose of 0.02 mg/kg. Blood samples were collected
      ten times for 24 hours after the drug administration. Digoxin concentrations were
      determined by FPIA method, and pharmacokinetic parameters were calculated by the
      two compartment open model for intragastric drug administration, and by the
      noncompartmental analysis for intravenous route. The levels of serum total
      bilirubin, creatinine, urea, glucose, albumin and activities of alanine,
      aspartate aminotransferases and alkaline phosphatase were estimated in all of the
      animals. The rabbits were sacrificed at the end of the study i.e. on the 7th day
      after the operation. The kidneys and the livers were weighed and examined macro-
      and microscopically. The laboratory tests as well as the anatomopathological
      investigations showed the symptoms of cholestasis and the hepatorenal syndrome
      (Tab. 2, 3). The blood serum concentrations of digoxin, both after intragastric
      and intravenous administration, were statistically higher during the whole
      observation period in the animals with obstructive cholestasis versus the
      controls (Tab. 4, 6). There were no significant alterations of digoxin parameters
      in the animals of the control groups, measured prior to and after the surgery. In
      the jaundiced animals, however, most of the pharmacokinetic parameters were
      markedly changed as compared with the preoperative values. In the rabbits which
      were given digoxin intragastrically, an increase in area under the plasma
      concentration-time curve (AUC) and in the peak concentration of the drug (Cmax)
      was noted (Tab. 5). Besides, the prolongation of mean residence time (MRT) and
      decrease in total body clearance (Cl) as well as apparent volume of distribution
      (Vz), were observed, as compared to the sham-operated controls. After the
      intravenous administration the following changes took place (Tab. 7): an increase
      in AUC, the prolongation of elimination half-life (t1/2 lambda z) and decrease in
      the total body clearance. All the above differences were statistically
      significant. Thus, digoxin, a drug predominantly eliminated via the kidney
      undergoes an impaired elimination in obstructive cholestasis. Basing on the
      results of the present study, the following statements could be expressed: (1)
      experimental, extrahepatic jaundice alters the pharmacokinetics of digoxin given
      intragastrically as well as intravenously; (2) the administration of therapeutic
      dose of digoxin in the state of mechanical jaundice may lead to its overdose; (3)
      obstruction of the common bile duct should indicate the necessity of monitoring
      the serum concentration of digoxin; (4) extrahepatic cholestasis may induce
      hepatorenal syndrome.

PMID- 9199127
TI  - [Evaluation of using statistical methods in selected national medical journals].
AB  - The paper covers the performed evaluation of frequency with which the statistical
      methods were applied in analyzed works having been published in six selected,
      national medical journals in the years 1988-1992. For analysis the following
      journals were chosen, namely: Klinika Oczna, Medycyna Pracy, Pediatria Polska,
      Polski Tygodnik Lekarski, Roczniki Panstwowego Zakladu Higieny, Zdrowie
      Publiczne. Appropriate number of works up to the average in the remaining medical
      journals was randomly selected from respective volumes of Pol. Tyg. Lek. The
      studies did not include works wherein the statistical analysis was not
      implemented, which referred both to national and international publications. That
      exemption was also extended to review papers, casuistic ones, reviews of books,
      handbooks, monographies, reports from scientific congresses, as well as papers on
      historical topics. The number of works was defined in each volume. Next, analysis
      was performed to establish the mode of finding out a suitable sample in
      respective studies, differentiating two categories: random and target selections.
      Attention was also paid to the presence of control sample in the individual
      works. In the analysis attention was also focussed on the existence of sample
      characteristics, setting up three categories: complete, partial and lacking. In
      evaluating the analyzed works an effort was made to present the results of
      studies in tables and figures (Tab. 1, 3). Analysis was accomplished with regard
      to the rate of employing statistical methods in analyzed works in relevant
      volumes of six selected, national medical journals for the years 1988-1992,
      simultaneously determining the number of works, in which no statistical methods
      were used. Concurrently the frequency of applying the individual statistical
      methods was analyzed in the scrutinized works. Prominence was given to
      fundamental statistical methods in the field of descriptive statistics (measures
      of position, measures of dispersion) as well as most important methods of
      mathematical statistics such as parametric tests of significance, analysis of
      variance (in single and dual classifications). non-parametric tests of
      significance, correlation and regression. The works, in which use was made of
      either multiple correlation or multiple regression or else more complex methods
      of studying the relationship for two or more numbers of variables, were
      incorporated into the works whose statistical methods were constituted by
      correlation and regression as well as other methods, e.g. statistical methods
      being used in epidemiology (coefficients of incidence and morbidity,
      standardization of coefficients, survival tables) factor analysis conducted by
      Jacobi-Hotellng's method, taxonomic methods and others. On the basis of the
      performed studies it has been established that the frequency of employing
      statistical methods in the six selected national, medical journals in the years
      1988-1992 was 61.1-66.0% of the analyzed works (Tab. 3), and they generally were
      almost similar to the frequency provided in English language medical journals. On
      a whole, no significant differences were disclosed in the frequency of applied
      statistical methods (Tab. 4) as well as in frequency of random tests (Tab. 3) in
      the analyzed works, appearing in the medical journals in respective years 1988
      1992. The most frequently used statistical methods in analyzed works for 1988
      1992 were the measures of position 44.2-55.6% and measures of dispersion 32.5
      38.5% as well as parametric tests of significance 26.3-33.1% of the works
      analyzed (Tab. 4). For the purpose of increasing the frequency and reliability of
      the used statistical methods, the didactics should be widened in the field of
      biostatistics at medical studies and postgraduation training designed for
      physicians and scientific-didactic workers.

PMID- 9199128
TI  - [The level of alcohol and titre of A and B group substances of the ABO system in
      blood samples infected by some strains of Escherichia coli].
AB  - Evaluating the results of sectional blood examinations for ethyl alcohol content
      is difficult due to the proceeding putrid and fermentative processes, in
      consequence of which endogenic ethyl alcohol is produced. Some difficulties also
      arise from estimating the results of serological investigations concerning the
      biological traces having been changed by putrefaction, where the presence of
      heterogenic antigens may be suspected. The putrid-fermentative processes are
      linked with the activity of microorganisms, particularly bacteria and yeast-like
      fungi. The first part of the paper deals with the bacterial flora in 50 sectional
      blood samples taken for routine determinations of ethyl alcohol content, thus
      with added sodium fluoride as bacteriostatic agent. The identification of the
      microorganisms cultured on differentiating and selectively differentiating media
      was carried out on the basis of the culture appearance, specimens stained by
      Gram's method, as well as biochemical examinations. From 16 studied samples of
      the sectional blood no strain of bacteria was cultured, mixed bacterial flora was
      isolated from the remaining ones (Tab. 1). Most numerous were Gram-negative
      bacteria (71%) among which E.coli appeared most frequently. Gram-positive claimed
      28% of the cultured microflora, while anaerobes hardly 4%. In the second part of
      the paper, the selected strains of E. coli pertaining to serological groups: 02,
      04, 06, 08, 09, 022, 025 were studied with regard to their possibility to produce
      ethanol as well as antigens A and B of AB0 system. E.coli strains were grown on
      broth medium containing glucose in concentration of from 0.00 to 27.75 mmol/l and
      human blood of 0 group collected from blood-donors on sodium citrate and CPD
      preservative with glucose in its content. Ethanol concentration in cultures was
      determined after 24 and 72 hours of incubation, by gas chromatography method, and
      glucose by enzymatic method. In serological investigations the material consisted
      of linen pieces being covered with 72-hour cultures of E.coli on broth and human
      blood of group 0. The study for the presence of the group substances A and B of
      AB0 system was performed by absorption method according to Holzer, and by
      absorption and elution method. In consequence of the studies it has been
      ascertained that sodium fluoride added as a bacteriostatic agent does not
      entirely inhibit the growth of bacteria, and especially bacteria Gram-negative
      appeared to be least sensitive to its action (Tab. 1). Selected strains of E.coli
      have differed with regard to the efficiency of ethanol production (Tab. 2). The
      level of produced ethanol depended on glucose concentration in the medium,
      temperature and the incubation time (Tab. 2, 3, 4 and Fig. 1). Under almost
      similar conditions the same strains produce more alcohol than on blood, which may
      give rise to supposition that the blood modifies the metabolism of bacteria (Tab.
      4 and 5). The cultures of selected strains studied failed to reveal the presence
      of heteroantigens with properties of antigen A and B of AB0 system.

PMID- 9199163
TI  - Chromatin dynamics in interphase nuclei and its implications for nuclear
      structure.
AB  - Translational dynamics of chromatin in interphase nuclei of living Swiss 3T3 and
      HeLa cells was studied using fluorescence microscopy and fluorescence recovery
      after photobleaching. Chromatin was fluorescently labeled using dihydroethidium,
      a membrane-permeant derivative of ethidium bromide. After labeling, a laser was
      used to bleach small (approximately 0.4 microm radius) spots in the
      heterochromatin and euchromatin of cells of both types. These spots were observed
      to persist for >1 h, implying that interphase chromatin is immobile over distance
      scales >/=0.4 microm. Over very short times (<1 s), a partial fluorescence
      recovery within the spots was observed. This partial recovery is attributed to
      independent dye motion, based on comparison with results obtained using ethidium
      homodimer-1, which binds essentially irreversibly to nucleic acids. The
      immobility observed here is consistent with chromosome confinement to domains in
      interphase nuclei. This immobility may reflect motion-impeding steric
      interactions that arise in the highly concentrated nuclear milieu or outright
      attachment of the chromatin to underlying nuclear substructures, such as
      nucleoli, the nuclear lamina, or the nuclear matrix.

PMID- 9199164
TI  - Physiological regulation of membrane protein sorting late in the secretory
      pathway of Saccharomyces cerevisiae.
AB  - In mammalian cells, extracellular signals can regulate the delivery of particular
      proteins to the plasma membrane. We have discovered a novel example of regulated
      protein sorting in the late secretory pathway of Saccharomyces cerevisiae. In
      yeast cells grown on either ammonia or urea medium, the general amino acid
      permease (Gap1p) is transported from the Golgi complex to the plasma membrane,
      whereas, in cells grown on glutamate medium, Gap1p is transported from the Golgi
      to the vacuole. We have also found that sorting of Gap1p in the Golgi is
      controlled by SEC13, a gene previously shown to encode a component of the COPII
      vesicle coat. In sec13 mutants grown on ammonia, Gap1p is transported from the
      Golgi to the vacuole, instead of to the plasma membrane. Deletion of PEP12, a
      gene required for vesicular transport from the Golgi to the prevacuolar
      compartment, counteracts the effect of the sec13 mutation and partially restores
      Gap1p transport to the plasma membrane. Together, these studies demonstrate that
      both a nitrogen-sensing mechanism and Sec13p control Gap1p transport from the
      Golgi to the plasma membrane.

PMID- 9199165
TI  - The lumenal domain of Sec63p stimulates the ATPase activity of BiP and mediates
      BiP recruitment to the translocon in Saccharomyces cerevisiae.
AB  - We studied the molecular nature of the interaction between the integral membrane
      protein Sec63p and the lumenal Hsp70 BiP to elucidate their role in the process
      of precursor transit into the ER of Saccharomyces cerevisiae. A lumenal stretch
      of Sec63p with homology to the Escherichia coli protein DnaJ is the likely region
      of interface between Sec63p and BiP. This domain, purified as a fusion protein
      (63Jp) with glutathione S-transferase (GST), mediated a stable ATP-dependent
      binding interaction between 63Jp and BiP and stimulated the ATPase activity of
      BiP. The interaction was highly selective because only BiP was retained on
      immobilized 63Jp when detergent-solubilized microsomes were mixed with ATP and
      the fusion protein. GST alone was inactive in these assays. Additionally, a GST
      fusion containing a point mutation in the lumenal domain of Sec63p did not
      interact with BiP. Finally, we found that the soluble Sec63p lumenal domain
      inhibited efficient precursor import into proteoliposomes reconstituted so as to
      incorporate both BiP and the fusion protein. We conclude that the lumenal domain
      of Sec63p is sufficient to mediate enzymatic interaction with BiP and that this
      interaction positioned at the translocation apparatus or translocon at the
      lumenal face of the ER is vital for protein translocation into the ER.

PMID- 9199166
TI  - Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery
      of post-Golgi vesicles.
AB  - The small GTPase Sec4p is required for vesicular transport at the post-Golgi
      stage of yeast secretion. Here we present evidence that mutations in SEC2, itself
      an essential gene that acts at the same stage of the secretory pathway, cause
      Sec4p to mislocalize as a result of a random rather than a polarized accumulation
      of vesicles. Sec2p and Sec4p interact directly, with the nucleotide-free
      conformation of Sec4p being the preferred state for interaction with Sec2p. Sec2p
      functions as an exchange protein, catalyzing the dissociation of GDP from Sec4
      and promoting the binding of GTP. We propose that Sec2p functions to couple the
      activation of Sec4p to the polarized delivery of vesicles to the site of
      exocytosis.

PMID- 9199167
TI  - The yeast v-SNARE Vti1p mediates two vesicle transport pathways through
      interactions with the t-SNAREs Sed5p and Pep12p.
AB  - Membrane traffic in eukaryotic cells requires that specific v-SNAREs on transport
      vesicles interact with specific t-SNAREs on target membranes. We identified a
      novel Saccharomyces cerevisiae v-SNARE (Vti1p) encoded by the essential gene,
      VTI1. Vti1p interacts with the prevacuolar t-SNARE Pep12p to direct Golgi to
      prevacuolar traffic. vti1-1 mutant cells missorted and secreted the soluble
      vacuolar hydrolase carboxypeptidase Y (CPY) rapidly and reversibly when vti1-1
      cells were shifted to the restrictive temperature. However, overexpression of
      Pep12p suppressed the CPY secretion defect exhibited by vti1-1 cells at 36
      degrees C. Characterization of a second vti1 mutant, vti1-11, revealed that Vti1p
      also plays a role in membrane traffic at a cis-Golgi stage. vti1-11 mutant cells
      displayed a growth defect and accumulated the ER and early Golgi forms of both
      CPY and the secreted protein invertase at the nonpermissive temperature.
      Overexpression of the yeast cis-Golgi t-SNARE Sed5p suppressed the accumulation
      of the ER form of CPY but did not lead to CPY transport to the vacuole in vti1-11
      cells. Overexpression of Sed5p allowed growth in the absence of Vti1p. In vitro
      binding and coimmunoprecipitation studies revealed that Vti1p interacts directly
      with the two t-SNAREs, Sed5p and Pep12p. These data suggest that Vti1p plays a
      role in cis-Golgi membrane traffic, which is essential for yeast viability, and a
      nonessential role in the fusion of Golgi-derived vesicles with the prevacuolar
      compartment. Therefore, a single v-SNARE can interact functionally with two
      different t-SNAREs in directing membrane traffic in yeast.

PMID- 9199168
TI  - The first 35 amino acids and fatty acylation sites determine the molecular
      targeting of endothelial nitric oxide synthase into the Golgi region of cells: a
      green fluorescent protein study.
AB  - Catalytically active endothelial nitric oxide synthase (eNOS) is located on the
      Golgi complex and in the caveolae of endothelial cells (EC). Mislocalization of
      eNOS caused by mutation of the N-myristoylation or cysteine palmitoylation sites
      impairs production of stimulated nitric oxide (NO), suggesting that intracellular
      targeting is critical for optimal NO production. To investigate the molecular
      determinants of eNOS targeting in EC, we constructed eNOS-green fluorescent
      protein (GFP) chimeras to study its localization in living and fixed cells. The
      full-length eNOS-GFP fusion colocalized with a Golgi marker, mannosidase II, and
      retained catalytic activity compared to wild-type (WT) eNOS, suggesting that the
      GFP tag does not interfere with eNOS localization or function. Experiments with
      different size amino-terminal fusion partners coupled to GFP demonstrated that
      the first 35 amino acids of eNOS are sufficient to target GFP into the Golgi
      region of NIH 3T3 cells. Additionally, the unique (Gly-Leu)5 repeat located
      between the palmitoylation sites (Cys-15 and -26) of eNOS is necessary for its
      palmitoylation and thus localization, but not for N-myristoylation, membrane
      association, and NOS activity. The palmitoylation-deficient mutants displayed a
      more diffuse fluorescence pattern than did WT eNOS-GFP, but still were associated
      with intracellular membranes. Biochemical studies also showed that the
      palmitoylation-deficient mutants are associated with membranes as tightly as WT
      eNOS. Mutation of the N-myristoylation site Gly-2 (abolishing both N
      myristoylation and palmitoylation) caused the GFP fusion protein to distribute
      throughout the cell as GFP alone, consistent with its primarily cytosolic nature
      in biochemical studies. Therefore, eNOS targets into the Golgi region of NIH 3T3
      cells via the first 35 amino acids, including N-myristoylation and palmitoylation
      sites, and its overall membrane association requires N-myristoylation but not
      cysteine palmitoylation. These results suggest a novel role for fatty acylation
      in the specific compartmentalization of eNOS and most likely, for other dually
      acylated proteins, to the Golgi complex.

PMID- 9199169
TI  - The Chlamydomonas mating type plus fertilization tubule, a prototypic cell fusion
      organelle: isolation, characterization, and in vitro adhesion to mating type
      minus gametes.
AB  - In the biflagellated alga Chlamydomonas, adhesion and fusion of the plasma
      membranes of gametes during fertilization occurs via an actin-filled, microvillus
      like cell protrusion. Formation of this approximately 3-microm-long fusion
      organelle, the Chlamydomonas fertilization tubule, is induced in mating type plus
      (mt+) gametes during flagellar adhesion with mating type minus (mt-) gametes.
      Subsequent adhesion between the tip of the mt+ fertilization tubule and the apex
      of a mating structure on mt- gametes is followed rapidly by fusion of the plasma
      membranes and zygote formation. In this report, we describe the isolation and
      characterization of fertilization tubules from mt+ gametes activated for cell
      fusion. Fertilization tubules were detached by homogenization of activated mt+
      gametes in an EGTA-containing buffer and purified by differential centrifugation
      followed by fractionation on sucrose and Percoll gradients. As determined by
      fluorescence microscopy of samples stained with a fluorescent probe for
      filamentous actin, the method yielded 2-3 x 10(6) fertilization tubules/microg
      protein, representing up to a 360-fold enrichment of these organelles.
      Examination by negative stain electron microscopy demonstrated that the purified
      fertilization tubules were morphologically indistinguishable from fertilization
      tubules on intact, activated mt+ gametes, retaining both the extracellular fringe
      and the internal array of actin filaments. Several proteins, including actin as
      well as two surface proteins identified by biotinylation studies, copurified with
      the fertilization tubules. Most importantly, the isolated mt+ fertilization
      tubules bound to the apical ends of activated mt- gametes between the two
      flagella, the site of the mt- mating structure; a single fertilization tubule
      bound per cell, binding was specific for gametes, and fertilization tubules
      isolated from trypsin-treated, activated mt+ gametes did not bind to activated mt
      gametes.

PMID- 9199170
TI  - IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links
      microfilaments.
AB  - Activated forms of the GTPases, Rac and Cdc42, are known to stimulate formation
      of microfilament-rich lamellipodia and filopodia, respectively, but the
      underlying mechanisms have remained obscure. We now report the purification and
      characterization of a protein, IQGAP1, which is likely to mediate effects of
      these GTPases on microfilaments. Native IQGAP1 purified from bovine adrenal
      comprises two approximately 190-kD subunits per molecule plus substoichiometric
      calmodulin. Purified IQGAP1 bound directly to F-actin and cross-linked the actin
      filaments into irregular, interconnected bundles that exhibited gel-like
      properties. Exogenous calmodulin partially inhibited binding of IQGAP1 to F
      actin, and was more effective in the absence, than in the presence of calcium.
      Immunofluorescence microscopy demonstrated cytochalasin D-sensitive
      colocalization of IQGAP1 with cortical microfilaments. These results, in
      conjunction with prior evidence that IQGAP1 binds directly to activated Rac and
      Cdc42, suggest that IQGAP1 serves as a direct molecular link between these
      GTPases and the actin cytoskeleton, and that the actin-binding activity of IQGAP1
      is regulated by calmodulin.

PMID- 9199172
TI  - Human Bcl-2 reverses survival defects in yeast lacking superoxide dismutase and
      delays death of wild-type yeast.
AB  - We expressed the human anti-apoptotic protein, Bcl-2, in Saccharomyces cerevisiae
      to investigate its effects on antioxidant protection and stationary phase
      survival. Yeast lacking copper-zinc superoxide dismutase (sod1Delta) show a
      profound defect in entry into and survival during stationary phase even under
      conditions optimal for survival of wild-type strains (incubation in water after
      stationary phase is reached). Expression of Bcl-2 in the sod1Delta strain caused
      a large improvement in viability at entry into stationary phase, as well as
      increased resistance to 100% oxygen and increased catalase activity. In addition,
      Bcl-2 expression reduced mutation frequency in both wild-type and sod1Delta
      strains. In another set of experiments, wild-type yeast incubated in expired
      minimal medium instead of water lost viability quickly; expression of Bcl-2
      significantly delayed this stationary phase death. Our results demonstrate that
      Bcl-2 has activities in yeast that are similar to activities it is known to
      possess in mammalian cells: (a) stimulation of antioxidant protection and (b)
      delay of processes leading to cell death.

PMID- 9199171
TI  - Kinetochore fiber maturation in PtK1 cells and its implications for the
      mechanisms of chromosome congression and anaphase onset.
AB  - Kinetochore microtubules (kMts) are a subset of spindle microtubules that bind
      directly to the kinetochore to form the kinetochore fiber (K-fiber). The K-fiber
      in turn interacts with the kinetochore to produce chromosome motion toward the
      attached spindle pole. We have examined K-fiber maturation in PtK1 cells using
      same-cell video light microscopy/serial section EM. During congression, the
      kinetochore moving away from its spindle pole (i.e., the trailing kinetochore)
      and its leading, poleward moving sister both have variable numbers of kMts, but
      the trailing kinetochore always has at least twice as many kMts as the leading
      kinetochore. A comparison of Mt numbers on sister kinetochores of congressing
      chromosomes with their direction of motion, as well as distance from their
      associated spindle poles, reveals that the direction of motion is not determined
      by kMt number or total kMt length. The same result was observed for oscillating
      metaphase chromosomes. These data demonstrate that the tendency of a kinetochore
      to move poleward is not positively correlated with the kMt number. At late
      prometaphase, the average number of Mts on fully congressed kinetochores is 19.7
      +/- 6.7 (n = 94), at late metaphase 24.3 +/- 4.9 (n = 62), and at early anaphase
      27.8 +/- 6.3 (n = 65). Differences between these distributions are statistically
      significant. The increased kMt number during early anaphase, relative to late
      metaphase, reflects the increased kMt stability at anaphase onset. Treatment of
      late metaphase cells with 1 microM taxol inhibits anaphase onset, but produces
      the same kMt distribution as in early anaphase: 28.7 +/- 7. 4 (n = 54). Thus, a
      full complement of kMts is not sufficient to induce anaphase onset. We also
      measured the time course for kMt acquisition and determined an initial rate of
      1.9 kMts/min. This rate accelerates up to 10-fold during the course of K-fiber
      maturation, suggesting an increased concentration of Mt plus ends in the vicinity
      of the kinetochore at late metaphase and/or cooperativity for kMt acquisition.

PMID- 9199174
TI  - Identification of a novel, putative Rho-specific GDP/GTP exchange factor and a
      RhoA-binding protein: control of neuronal morphology.
AB  - The small GTP-binding protein Rho has been implicated in the control of neuronal
      morphology. In N1E-115 neuronal cells, the Rho-inactivating C3 toxin stimulates
      neurite outgrowth and prevents actomyosin-based neurite retraction and cell
      rounding induced by lysophosphatidic acid (LPA), sphingosine-1-phosphate, or
      thrombin acting on their cognate G protein-coupled receptors. We have identified
      a novel putative GDP/GTP exchange factor, RhoGEF (190 kD), that interacts with
      both wild-type and activated RhoA, but not with Rac or Cdc42. RhoGEF, like
      activated RhoA, mimics receptor stimulation in inducing cell rounding and in
      preventing neurite outgrowth. Furthermore, we have identified a 116-kD protein,
      p116(Rip), that interacts with both the GDP- and GTP-bound forms of RhoA in N1E
      115 cells. Overexpression of p116(Rip) stimulates cell flattening and neurite
      outgrowth in a similar way to dominant-negative RhoA and C3 toxin. Cells
      overexpressing p116(Rip) fail to change their shape in response to LPA, as is
      observed after Rho inactivation. Our results indicate that (a) RhoGEF may link G
      protein-coupled receptors to RhoA activation and ensuing neurite retraction and
      cell rounding; and (b) p116(Rip) inhibits RhoA-stimulated contractility and
      promotes neurite outgrowth.

PMID- 9199173
TI  - Brain myosin V is a synaptic vesicle-associated motor protein: evidence for a
      Ca2+-dependent interaction with the synaptobrevin-synaptophysin complex.
AB  - Brain myosin V is a member of a widely distributed class of unconventional
      myosins that may be of central importance to organelle trafficking in all
      eukaryotic cells. Molecular constituents that target this molecular motor to
      organelles have not been previously identified. Using a combination of
      immunopurification, extraction, cross-linking, and coprecipitation assays, we
      demonstrate that the tail domain of brain myosin V forms a stable complex with
      the synaptic vesicle membrane proteins, synaptobrevin II and synaptophysin. While
      myosin V was principally bound to synaptic vesicles during rest, this putative
      transport complex was promptly disassembled upon the depolarization-induced entry
      of Ca2+ into intact nerve endings. Coimmunoprecipitation assays further indicate
      that Ca2+ disrupts the in vitro binding of synaptobrevin II to synaptophysin in
      the presence but not in the absence of Mg2+. We conclude that hydrophilic forces
      reversibly couple the myosin V tail to a biochemically defined class of
      organelles in brain nerve terminals.

PMID- 9199175
TI  - Delayed development of nervous system in mice homozygous for disrupted
      microtubule-associated protein 1B (MAP1B) gene.
AB  - Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated
      proteins (MAPs), is a major component of the neuronal cytoskeleton. It is
      expressed at high levels in immature neurons during growth of their axons, which
      indicates that it plays a crucial role in neuronal morphogenesis and neurite
      extension. To better define the role of MAP1B in vivo, we have used gene
      targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption
      exhibit no overt abnormalities in their development and behavior, while
      homozygotes showed a slightly decreased brain weight and delayed nervous system
      development. Our data indicate that while MAP1B is not essential for survival, it
      is essential for normal time course development of the murine nervous system.
      These conclusions are very different from those of a previous MAP1B gene
      targeting study (Edelmann, W., M. Zervas, P. Costello, L. Roback, I. Fischer, A.
      Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl.
      Acad. Sci. USA. 93: 1270-1275). In this previous effort, homozygotes died before
      reaching 8-d embryos, while heterozygotes showed severely abnormal phenotypes in
      their nervous systems. Because the gene targeting event in these mice produced a
      gene encoding a 571-amino acid truncated product of MAP1B, it seems likely that
      the phenotypes seen arise from the truncated MAP1B product acting in a dominant
      negative fashion, rather than a loss of MAP1B function.

PMID- 9199176
TI  - Induced expression of trimerized intracellular domains of the human tumor
      necrosis factor (TNF) p55 receptor elicits TNF effects.
AB  - The various biological activities of tumor necrosis factor (TNF) are mediated by
      two receptors, one of 55 kD (TNF-R55) and one of 75 kD (TNF-R75). Although the
      phenotypic and molecular responses elicited by TNF in different cell types are
      fairly well characterized, the signaling pathways leading to them are so far only
      partly understood. To further unravel these processes, we focused on TNF-R55,
      which is responsible for mediating most of the known TNF effects. Since several
      studies have demonstrated the importance of receptor clustering and consequently
      of close association of the intracellular domains for signaling, we addressed the
      question of whether clustering of the intracellular domains of TNF-R55 (TNF-R55i)
      needs to occur in structural association with the inner side of the cell
      membrane, where many signaling mediators are known to reside. Therefore, we
      investigated whether induced intracellular clustering of only TNF-R55i would be
      sufficient to initiate and generate a full TNF response, without the need for a
      full-length receptor molecule or a transmembrane region. Our results provide
      clear evidence that inducible forced trimerization of either TNF-R55i or only the
      death domain elicits an efficient TNF response, comprising activation of the
      nuclear factor kappaB, induction of interleukin-6, and cell killing.

PMID- 9199177
TI  - ZAP-70 protein tyrosine kinase is constitutively targeted to the T cell cortex
      independently of its SH2 domains.
AB  - ZAP-70 is a nonreceptor protein tyrosine kinase that is essential for signaling
      via the T cell antigen receptor (TCR). ZAP-70 becomes phosphorylated and
      activated by LCK protein tyrosine kinase after interaction of its two NH2
      terminal SH2 domains with tyrosine-phosphorylated subunits of the activated TCR.
      In this study, the localization of ZAP-70 was investigated by immunofluorescence
      and confocal microscopy. ZAP-70 was found to be localized to the cell cortex in a
      diffuse band under the plasma membrane in unstimulated T cells, and this
      localization was not detectably altered by TCR stimulation. Analysis of mutants
      indicated that ZAP-70 targeting was independent of its SH2 domains but required
      its active kinase domain. The specific compartmentalization of ZAP-70 suggests
      that it may interact with an anchoring protein in the cell cortex via its hinge
      or kinase domains. It is likely that the maintenance of high concentrations of
      ZAP-70 at the cell cortex, that only has to move a short distance to interact
      with phophorylated TCR subunits, facilitates rapid initiation of signaling by the
      TCR. In addition, as the major increase in tyrosine phosphorylation induced by
      the TCR also occurs at the cell cortex (Ley, S.C., M. Marsh, C.R. Bebbington, K.
      Proudfoot, and P. Jordan. 1994. J. Cell. Biol. 125:639-649), ZAP-70 may be
      localized close to its downstream targets.

PMID- 9199178
TI  - Dynamics of beta-catenin interactions with APC protein regulate epithelial
      tubulogenesis.
AB  - Epithelial tubulogenesis involves complex cell rearrangements that require
      control of both cell adhesion and migration, but the molecular mechanisms
      regulating these processes during tubule development are not well understood.
      Interactions of the cytoplasmic protein, beta-catenin, with several molecular
      partners have been shown to be important for cell signaling and cell-cell
      adhesion. To examine if beta-catenin has a role in tubulogenesis, we tested the
      effect of expressing NH2-terminal deleted beta-catenins in an MDCK epithelial
      cell model for tubulogenesis. After one day of treatment, hepatocyte growth
      factor/scatter factor (HGF/ SF)-stimulated MDCK cysts initiated tubulogenesis by
      forming many long cell extensions. Expression of NH2-terminal deleted beta
      catenins inhibited formation of these cell extensions. Both DeltaN90 beta
      catenin, which binds to alpha-catenin, and DeltaN131 beta-catenin, which does not
      bind to alpha-catenin, inhibited formation of cell extensions and tubule
      development, indicating that a function of beta-catenin distinct from its role in
      cadherin-mediated cell-cell adhesion is important for tubulogenesis. In cell
      extensions from parental cysts, adenomatous polyposis coli (APC) protein was
      localized in linear arrays and in punctate clusters at the tips of extensions.
      Inhibition of cell extension formation correlated with the colocalization and
      accumulation of NH2-terminal deleted beta-catenin in APC protein clusters and the
      absence of linear arrays of APC protein. Continued HGF/ SF treatment of parental
      cell MDCK cysts resulted in cell proliferation and reorganization of cell
      extensions into multicellular tubules. Similar HGF/SF treatment of cysts derived
      from cells expressing NH2-terminal deleted beta-catenins resulted in cells that
      proliferated but formed cell aggregates (polyps) within the cyst rather than
      tubules. Our results demonstrate an unexpected role for beta-catenin in cell
      migration and indicate that dynamic beta-catenin-APC protein interactions are
      critical for regulating cell migration during epithelial tubulogenesis.

PMID- 9199180
TI  - Calcineurin: not just a simple protein phosphatase.
AB  - Calcineurin is a Ca2+ calmodulin dependent protein phosphatase which has an
      important role in the control of intracellular Ca2+ signalling. The protein is a
      heterodimer of one catalytic (CnA) subunit and one regulatory (CnB) subunit. As
      suggested by the protein sequence and confirmed by the crystallographic
      structure, the catalytic subunit of calcineurin (CnA) has high homologies with
      other protein phosphatases. The regulatory subunit (CnB) belongs to the EF-hand
      Ca2+ binding protein family. Despite its similarity with calmodulin, it has a
      different tertiary structure. Calcineurin is the target of two important
      immunosuppressant drugs: cyclosporin A and FK506. Subsequently, a detailed
      clarification of the role of calcineurin in the cytokine mediated activation of
      the T-cells has been possible. The understanding of the role of calcineurin in
      other cells, in particular neurons, is also progressing rapidly.

PMID- 9199179
TI  - Cross talk between adhesion molecules: control of N-cadherin activity by
      intracellular signals elicited by beta1 and beta3 integrins in migrating neural
      crest cells.
AB  - During embryonic development, cell migration and cell differentiation are
      associated with dynamic modulations both in time and space of the repertoire and
      function of adhesion receptors, but the nature of the mechanisms responsible for
      their coordinated occurrence remains to be elucidated. Thus, migrating neural
      crest cells adhere to fibronectin in an integrin-dependent manner while
      maintaining reduced N-cadherin-mediated intercellular contacts. In the present
      study we provide evidence that, in these cells, the control of N-cadherin may
      rely directly on the activity of integrins involved in the process of cell
      motion. Prevention of neural crest cell migration using RGD peptides or
      antibodies to fibronectin and to beta1 and beta3 integrins caused rapid N
      cadherin-mediated cell clustering. Restoration of stable intercellular contacts
      resulted essentially from the recruitment of an intracellular pool of N-cadherin
      molecules that accumulated into adherens junctions in tight association with the
      cytoskeleton and not from the redistribution of a preexisting pool of surface N
      cadherin molecules. In addition, agents that cause elevation of intracellular
      Ca2+ after entry across the plasma membrane were potent inhibitors of cell
      aggregation and reduced the N-cadherin- mediated junctions in the cells. Finally,
      elevated serine/ threonine phosphorylation of catenins associated with N-cadherin
      accompanied the restoration of intercellular contacts. These results indicate
      that, in migrating neural crest cells, beta1 and beta3 integrins are at the
      origin of a cascade of signaling events that involve transmembrane Ca2+ fluxes,
      followed by activation of phosphatases and kinases, and that ultimately control
      the surface distribution and activity of N-cadherin. Such a direct coupling
      between adhesion receptors by means of intracellular signals may be significant
      for the coordinated interplay between cell-cell and cell-substratum adhesion that
      occurs during embryonic development, in wound healing, and during tumor invasion
      and metastasis.

PMID- 9199181
TI  - Sequence and copy number of the Xanthomonas campestris pv. campestris gene
      encoding 16S rRNA.
AB  - A 6.7-kb Sau3A1 fragment containing ribosomal RNA genes was cloned from the
      chromosome of Xanthomonas campestris pv. campestris strain 17 by a PCR-based
      strategy. Nucleotide sequence was determined for the 16S rRNA gene (1,544 nt).
      This gene has a G+C content of 54.9% which is similar to the 16S rRNA genes of
      Escherichia coli and Pseudomonas aeruginosa but different from the value reported
      for the whole X. campestris chromosome (64%). Sequence alignment revealed that
      AGGAGG is consensus for ribosome binding, with the internal GGAG to be paired
      most frequently with the anti-Shine-Dalgarno sequence. This consensus sequence
      was found in the regions upstream from the initiation codon of 98 Xanthomonas
      genes among 116 aligned, but not in the remaining genes. This suggests that about
      16% of the Xanthomonas genes do not possess typical ribosome binding sites and
      another mechanism may be required for recognition of correct translation
      initiation sites. Two rrn operons were detected in Xc17 chromosome by pulsed
      field gel electrophoresis and Southern hybridization.

PMID- 9199182
TI  - Advanced glycation end products induce specific glycoprotein alterations in
      retinal microvascular cells.
AB  - In order to investigate the mechanisms involved in diabetic retinopathy, we
      studied the effects of advanced glycosylation end products (AGE) on retinal
      microvascular cell glycoproteins. Bovine retinal pericytes (BRP) and endothelial
      cells (BREC) were incubated in the presence of AGE-modified albumin and cell
      glycoproteins analyzed by lectin affinoblotting and metabolic radiolabeling with
      sugar precursors. Selective modifications in the glycoprotein sugar chains were
      observed mainly in BREC and for a 210 kDa membrane glycoprotein. Indeed, a 40%
      decrease of alpha(2,3) sialic acid, beta(1,3) galactose or alpha(1,6) fucose
      content was observed without significant protein amount changes. These
      glycoprotein alterations were related to the concentration of AGE. Neither BRP
      nor BREC glycoproteins were modified when cells were incubated with high glucose
      or fructose concentrations. These results suggest a new diabetic pathogenic
      mechanism in which a protein post-translational modification, in this case
      glycation, could modify another post-translational process such as the enzymatic
      glycosylation.

PMID- 9199183
TI  - Increased oxidative damage to mitochondrial DNA following chronic ethanol
      consumption.
AB  - Ethanol consumption adversely affects the structural and functional integrity of
      hepatic mitochondria. Some of these effects may arise from the increased cellular
      levels of oxidizing radicals induced by ethanol feeding. Since DNA is a potential
      target of free radical damage, we investigated the effect of chronic ethanol
      feeding on oxidative modification of mtDNA. Mitochondria were isolated from the
      livers of control and ethanol-fed rats and the mtDNA analyzed for the presence of
      8-hydroxydeoxyguanosine (8-OHdG). A 21% increase in the level of 8-OHdG was
      detected in mtDNA from animals that had been fed an ethanol-containing diet for
      42-76 days (control, 3.98 +/- 0.5; ethanol, 4.8 +/- 0.9 8-OHdG/100,000dG). This
      difference increased to 43% in animals that had been fed ethanol for 105-164 days
      (control, 6.9 +/- 1.0; ethanol, 9.9 +/- 1.1 8-OHdG/100,000dG). This increase in
      mtDNA oxidation was accompanied by a decrease in the recovery of mtDNA (42-76
      days: control, 88 +/- 11; ethanol 76 +/- 8 ng/mg mitochondrial protein; 105-164
      days: control, 88 +/- 13; ethanol 62 +/- 14 ng/mg mitochondrial protein). The
      data presented demonstrate that chronic ethanol feeding leads to increased
      oxidative damage of hepatic mtDNA. This may in turn result in progressive mtDNA
      mutations and deletions and impaired mitochondrial function.

PMID- 9199184
TI  - Action of mitochondrial endonuclease G on DNA damaged by L-ascorbic acid,
      peplomycin, and cis-diamminedichloroplatinum (II).
AB  - Mitochondrial DNA (mtDNA) suffers extensive damage from the environment, however,
      the enzymes involved in the repair of mtDNA are still unknown. Here, we partially
      purified mitochondrial endonuclease G (Endo G) from the bovine heart, and
      examined the action of Endo G on damaged DNA. Treatment of DNA with L-ascorbic
      acid or peplomycin, that introduces single-strand breaks through active oxygen
      radicals, greatly enhanced the susceptibility to nucleolytic attacks from Endo G.
      The enzyme cleaved at or near sites where single-strand breaks were present in
      the opposite strand. Cisplatin-mediated DNA damage, which causes intrastrand
      crosslinks between adjacent guanine residues, also facilitated Endo G digestion,
      indicating that the enzyme can recognize local distortions in the duplex DNA
      introduced by adducts. These nucleolytic properties of Endo G in vitro suggest
      its possible involvement in the maintenance of mtDNA by eliminating defective
      genomes from the multicopy pool.

PMID- 9199186
TI  - Molecular characterization of the gene coding for threonine dehydrogenase in
      Xanthomonas campestris.
AB  - The Xanthomonas campestris pv. campestris 17 gene tdh, which codes for the
      threonine dehydrogenase (TDH), was cloned and sequenced. The deduced gene
      product, a polypeptide consisting of 340 amino acids (Mr = 37,048), has 63.5%
      identity to the E. coli TDH in amino acid sequence and shares residue
      conservation with the alcohol/polyol dehydrogenases from different organisms. TDH
      activity was not detectable in the tdh mutant constructed by gene replacement;
      however, the enzyme activity in the mutant complemented in trans by a plasmid
      containing the complete tdh sequence was increased by 15 folds over Xc17.
      Northern blot analysis detected an mRNA with a size similar to that of the Xc17
      tdh coding region, suggesting that the tdh gene-containing transcript may be
      monocistronic.

PMID- 9199185
TI  - Non-genomic mechanisms of glucocorticoid inhibition of adrenocorticotropin
      secretion: possible involvement of GTP-binding protein.
AB  - We investigated non-genomic mechanisms of glucocorticoid negative feedback
      regulation on pituitary corticotroph cells using the AtT20 mouse corticotroph
      tumor cell line. A synthetic glucocorticoid dexamethasone (100 nM) potently
      suppressed forskolin-induced cAMP generation, adrenocorticotropin (ACTH)
      secretion, and proopiomelanocortin gene expression. When de novo gene expression
      was inhibited by actinomycin D (1 microM), dexamethasone still suppressed cAMP
      efflux and ACTH release, although less potently. Interestingly, under the same
      conditions, pretreatment of the cells with pertussis toxin (50 ng/ml) completely
      abolished the suppressive effect of dexamethasone on both parameters. These
      results suggest that non-genomic and genomic mechanisms are involved in the
      glucocorticoid negative regulation of ACTH expression, and a pertussis toxin
      sensitive GTP-binding protein might, at least partly, participate in the non
      genomic effect.

PMID- 9199187
TI  - Generation of active oxygen species from advanced glycation end-products (AGE)
      under ultraviolet light A (UVA) irradiation.
AB  - To clarify a possible role of advanced glycation end-products (AGE) on photoaging
      of human skin, the interaction between AGE and ultraviolet A light (UVA) was
      examined from both a biological and chemical perspective. Human dermal
      fibroblasts that were exposed to UVA in the presence of AGE bound with bovine
      serum albumin (AGE-BSA) exhibited a significant decrease of cell viability as
      compared to control cells, which were exposed to UVA in the absence of AGE-BSA.
      Further, UVA-irradiated AGE-BSA reduced nitroblue tetrazolium to its formazan,
      but the reaction was inhibited by addition of superoxide dismutase in the system.
      UVA dose-dependent formation of H2O2 in AGE-BSA was also observed. An ESR spin
      trapping study revealed the generation of unstable free radicals in AGE-BSA under
      UVA irradiation. After addition of Fe2+ in the system, an ESR spectrum due to the
      formation of hydroxyl radicals was observed. On the basis of these results, the
      authors propose that AGE is an important factor for promoting photoaging in the
      skin via generation of active oxygen species involving .O2-, H2O2, and .OH.

PMID- 9199188
TI  - Accelerated endothelialization by local delivery of recombinant human vascular
      endothelial growth factor reduces in-stent intimal formation.
AB  - Endothelium plays an important role in vascular smooth muscle cell proliferation
      and thrombus deposition. We thus hypothesized that local delivery of recombinant
      human vascular endothelial growth factor (rhVEGF) might reduce in-stent intimal
      formation. Balloon injury followed by Palmaz-Schatz stent implantation was
      performed in the external iliac artery of 30 New Zealand rabbits. Animals were
      then randomized to: 1) no local delivery (Control group, n=10); 2) local delivery
      via a channel balloon catheter of 100 microg rhVEGF165 (VEGF group, n=10); or 3)
      local delivery of the vehicle solution (Vehicle group, n=10). Animals were
      sacrificed 28 days later and morphometric analysis was performed. Maximal intimal
      area was reduced from 1.47+/-0.12 mm2 and 1.44+/-0.10 mm2 in the Control and
      Vehicle groups, respectively, to 0.87+/-0.06 mm2 in the VEGF group (p<.001).
      Accelerated endothelialization by local delivery of an endothelial-specific
      growth factor, rhVEGF, significantly reduces in-stent intimal formation and could
      constitute an attractive alternative to direct antiproliferative strategies.

PMID- 9199190
TI  - Cloning and characterization of the 5'-flanking region of the human dopamine D4
      receptor gene.
AB  - Dopamine D4 receptor (DRD4) has received attention in terms of pathogenesis of
      schizophrenia and association with human personalities. We isolated the human
      DRD4 gene containing the 5'-flanking region and determined its sequence. Analysis
      of the DRD4 transcripts by 5'-RACE (5'-rapid amplification of cDNA ends) revealed
      a region of the transcription initiation located between -501 and -436 relative
      to the first nucleotide of the initiation codon. There is a CpG island spanning
      from -900 to +500 but no TATA or CAAT boxes in the 5'-flanking region. Functional
      analysis of the 5'-flanking region of the DRD4 gene by a transient expression
      method revealed the presence of a negative modulator between -770 and -679. The
      region between -591 and -123 gave the highest transcriptional activity in IMR32
      (neuroblastoma) and Y-79 (retinoblastoma) cells but not in HeLa cells, suggesting
      that this housekeeping gene-like promoter regulates the cell-type specific gene
      expression.

PMID- 9199189
TI  - Novel pathway of insulin signaling involving Stat1alpha in Hep3B cells.
AB  - STAT proteins are important transcription factors that regulate cell growth and
      differentiation. To elucidate the molecular mechanisms of insulin actions, we
      have studied how insulin activates STAT proteins in Hep3B cells. Insulin rapidly
      phosphorylated Stat1alpha at tyrosine residues and increased its specific binding
      activities to a GAS/ISRE consensus oligonucleotide. IL-4 also phosphorylated
      Stat1alpha and increased DNA binding activities to the same Stat1alpha responsive
      element. There was no increase in tyrosine phosphorylation of JAK family of
      kinases following insulin stimulation. In contrast, IL-4 stimulated tyrosine
      phosphorylation of JAK1, JAK2 and tyk2 in this cell line. These data indicate
      that insulin receptor signaling can activate the transcriptional regulatory
      function of STAT protein, and that insulin actions on Stat1alpha are mediated
      through signaling pathways independent of JAK family of kinases.

PMID- 9199191
TI  - Molecular cloning and expression of human alpha2,8-sialyltransferase (hST8Sia V).
AB  - The cDNA encoding human alpha2,8-sialyltransferase (hST8Sia V) which exhibits
      activity toward gangliosides, GM1b, GD1a, GT1b, and GD3, was isolated by
      screening of human brain cDNA library with a DNA probe generated from the cDNA
      sequence of mouse ST8Sia V (mST8Sia V) and by 5'-RACE of mRNA from human brain
      tissue. Comparative analysis of this cDNA with mST8Sia V showed that each
      sequence of the predicted coding region contains 84% identity in both nucleotide
      and amino acid. Northern analysis of this cDNA indicated that, in contrast to
      mST8Sia V, two different sizes of transcripts corresponding to 11 and 2.5 kb were
      expressed in both human fetal and adult brain, while the transcript of 2.5 kb was
      detected only in adult heart and skeletal muscle. The enzyme expressed in COS
      cells showed a substrate specificity very similar to that of mST8Sia V.

PMID- 9199192
TI  - Facilitation of Ca2+ action potential frequency by a small G protein Rab3A in rat
      pituitary GH3 cells.
AB  - GH3 pituitary cells have high tendency to exhibit spontaneous Ca2+ action
      potentials and their frequency (Ca2+ APF) is increased by treatment with
      thyrotropin-releasing hormone (TRH). Although spontaneous Ca2+ firing was thought
      to be significant for the induction of oscillations in cytosolic Ca2+
      concentration ([Ca2+]i), little attempt to elucidate the mechanism has been done
      so far. We demonstrate here that spontaneous Ca2+ APF in GH3 cells was increased
      1.5-3 fold, comparable to that for TRH, by injection of guanosine 5'-0-3
      thiotriphosphate (GTPgammaS), rab3A effector domain peptide, and phorbol
      dibutyrate (PDBu), whereas guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), H-rab5
      peptide, ras peptide, and 4 alpha-phorbol did not. The enhancement of Ca2+ firing
      by rab3A effector domain peptide was blocked by a protein kinase C (PKC)
      inhibitor, PKC(19-36). The present study suggests that the spontaneous Ca2+APF
      may be controlled by small G protein phosphorylated by PKC.

PMID- 9199193
TI  - Synergistic responses of steroidal estrogens in vitro (yeast) and in vivo
      (turtles).
AB  - Many environmental agents exert estrogenic activity. Previous studies from our
      laboratories demonstrated that certain combinations of environmental estrogens
      (i) reverse the sex of male turtle embryos in a synergistic manner (Bergeron et
      al., (1994) Environ. Hlth Perspect. 102, 780-782), and (ii) synergistically
      transactivate the human estrogen receptor (hER) in yeast and mammalian cells
      (Arnold et al., (1996) Science 272, 1489-1492). Because our findings with
      synthetic estrogens suggested that combinations of naturally-occurring steroidal
      estrogens might also produce synergistic activity of the ER, we used the same
      model systems to measure the activity of combinations of steroidal estrogens. The
      activity of combinations of estrone, estradiol-17beta or estradiol-17alpha in
      yeast strains expressing hER was synergistic at submaximal concentrations of both
      estrogenic compounds. However, synergy was not observed with mixtures of
      estrogens when the concentration of one of the estrogens alone was maximally
      active in yeast. Ligand-binding assays in yeast performed with various
      radiolabeled estrogens suggested that multiple estrogens may interact with the
      receptor. The estrogen-dependent process of sex-reversal of turtle embryos
      incubated at a male-producing temperature was used to determine whether steroidal
      estrogens also had synergistic activity in vivo. In this instance, a combination
      of estriol and estradiol-17beta was effective in reversing the gonadal sex of
      turtle embryos from males to females in a synergistic manner. Our results suggest
      that the synergy of some combinations of estrogens, synthetic or steroidal, may
      play a role in the estrogen-dependent process of sexual development in certain
      species.

PMID- 9199194
TI  - Novel quantitative trait loci for blood pressure and related traits on rat
      chromosomes 1, 10, and 18.
AB  - Hypertension and diabetes mellitus are known to be frequently associated. The
      genetic dissection of diseases such as hypertension or diabetes mellitus is
      possible by using experimental crosses, which allow identification of loci
      influencing phenotypic traits (quantitative trait loci - QTLs). In this study the
      spontaneously hypertensive rat (SHR) and spontaneously diabetic, but normotensive
      rat (BB/OK) were crossed and the F2 population was analysed in order to search
      for QTLs on selected chromosomes (1, 10, 18) for blood pressure and some
      metabolic traits related to diabetes, renal function and hypertension. There were
      3 regions found on chromosome 1 which showed linkage to blood pressure. The
      strongest evidence for linkage was observed between loci Igf2 and D1Mgh12. On
      chromosome 10 there was a QTL for blood pressure found between Ppy and Abp and on
      chromosome 18 there were three regions (Ttr-Grl, Tilp-Gja1, Olf-D18Mit9) with
      linkage to blood pressure. Since the 24 hr albumin and phosphate excretion
      correlated with blood pressure in F2 hybrids, the same regions were linked to
      both parameters. Region with linkage to serum concentrations of cholesterol
      (probably located beyond the terminal marker Ttr of the linkage group) were also
      found. The results of this study with a new F2(BB x SHR) population confirm the
      existence of previously described blood pressure loci (Sa and Bp2) and showed
      novel QTLs on chromosomes 1, 10 and 18.

PMID- 9199195
TI  - The mitochondrion as a primary site of action of glucocorticoids: mitochondrial
      nucleotide sequences, showing similarity to hormone response elements, confer
      dexamethasone inducibility to chimaeric genes transfected in LATK- cells.
AB  - The hypothesis of a primary action of steroid hormones on mitochondrial gene
      expression has been supported by the detection of the glucocorticoid receptor in
      liver mitochondria and the demonstration of the interaction of the receptor with
      putative mitochondrial HREs. We now show that two putative mitochondrial
      glucocorticoid response elements present within the cytochrome oxidase subunit I
      gene (GREI and GREII), linked to a thymidine kinase promoter and to the CAT gene,
      transfected to LATK- cells, confer dexamethasone inducibility to the CAT gene. As
      the plasmids were stably transfected, hormone induction was analysed in the
      nuclear background. This effect is dose dependent and is abolished by the
      glucocorticoid antagonist RU38486.

PMID- 9199196
TI  - Multiple cadherins are expressed in human fibroblasts.
AB  - Although the cell-cell adhesiveness of fibroblasts is thought to be related to
      wound healing, the molecular basis of this adhesiveness is still unknown. We
      isolated five kinds of cadherin fragments from the cDNA of human fibroblasts by
      polymerase chain reaction (PCR). Two of the five were known cadherins: PC43, a
      protocadherin containing six cadherin repeats in the extracelluar domain, and
      human Fat, which is the human homologue of the Drosophila tumor suppressor Fat.
      The other three were novel cadherin fragments, and we named them cadherins FIB1,
      FIB2, and FIB3. The expressions of cadherins including E-, P-, and N-cadherin,
      PC43, human Fat, and cadherins FIB1, FIB2, and FIB3 were compared in human
      fibroblasts, human melanocytes, and human epidermal keratinocytes. The latter six
      cadherins were expressed in human fibroblasts, and cadherins FIB1 and FIB2 were
      fibroblast-specific. These results suggest that diverse cadherin molecules may
      contribute to the cell-cell adhesion in human fibroblasts.

PMID- 9199197
TI  - Significant downregulation of the major swine xenoantigen by N
      acetylglucosaminyltransferase III gene transfection.
AB  - Introduction of the beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III
      (GnT-III) gene into swine endothelial cells (SEC) reduced their susceptibility to
      normal human serum (NHS) in complement-mediated cell lysis and also suppressed
      the antigenicity to human natural antibodies as evidenced by flow cytometric
      analysis, as well as Griffonia simplicifolia 1 isolectin (1B4 lectin) binding to
      the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (the alpha-galactosyl epitope). Western
      blot analysis indicated that proteins smaller than 66 kDa had diminished
      reactivity to NHS and 1B4 lectin. GnT-III, a key enzyme involved in branch
      formation of N-linked sugars, was found to downregulate the expression of
      xenoantigen, suggesting that this approach may be of value in clinical
      xenotransplantation in the future.

PMID- 9199198
TI  - Activation of NFkappaB is essential but not sufficient to stimulate mitogenesis
      of vascular smooth muscle cells.
AB  - This study investigates the role of the transcription factor NFkappaB in thrombin
      and thrombin receptor activating peptide (TRAP, SFLLRNPNDKYEPYF)-induced
      mitogenesis of cultured bovine coronary artery smooth muscle cells (SMC).
      Stimulation of resting cells by thrombin (10 nM) or TRAP (10-100 microM) resulted
      in a comparable time-dependent activation of NFkappaB as detected by Western
      blotting and electrophoretic mobility shift assay (EMSA) of nuclear extracts. The
      NFkappaB activation was antagonized by N-acetyl-L-cysteine (20 mM) and
      pentoxifylline (0.5 mM). Thrombin caused a 3-4-fold increase in [3H]thymidine
      incorporation within 24 h which was prevented by inhibitors of NFkappaB
      activation. In contrast, TRAP did not cause any mitogenic response. These results
      demonstrate that activation of NFkappaB is an essential but not a sufficient
      signal for SMC mitogenesis.

PMID- 9199199
TI  - Glycosaminoglycans can influence fibroblast growth factor-2 mitogenicity without
      significant growth factor binding.
AB  - Fibroblast growth factors are important heparin binding, mitogenic proteins. The
      binding site in heparin and heparan sulfate for fibroblast growth factor-2 (basic
      fibroblast growth factor) has been described as rich in glucosamine-2-sulfate 1-
      >4 linked to iduronic acid-2-sulfate. The glucosamine residue in the heparin
      binding site is also 6-sulfated. A new glycosaminoglycan, acharan sulfate, has
      been chemically modified to prepare a polysaccharide, N-sulfoacharan sulfate,
      consisting of glucosamine-2-sulfate 1-->4 linked to iduronic acid-2-sulfate.
      Acharan sulfate binds very weakly to fibroblast growth factor-2 while N
      sulfoacharan sulfate binds with nearly the same affinity as heparin. Mitogenicity
      studies were performed using heparan sulfate-free cells stably transfected with
      fibroblast growth factor receptor-1. Acharan sulfate inhibits heparin's
      enhancement of fibroblast growth factor-2 mitogenic activity, without affecting
      cell viability, while N-sulfoacharan sulfate shows heparin-like activity but at a
      greatly reduced level. These results suggest additional mechanisms not requiring
      high affinity glycosaminoglycan binding to fibroblast growth factor-2 may be
      important in its mitogenic activity.

PMID- 9199200
TI  - 5-HPETE is a potent inhibitor of neuronal Na+, K(+)-ATPase activity.
AB  - The effects of 1 microM concentrations of arachidonic acid hydroperoxide (HPETES)
      products of 5-, 12- and 15-lipoxygenase on Na+, K(+)-ATPase activity were
      investigated in synaptosomal membrane preparations from rat cerebral cortex. 5
      HPETE inhibited Na+, K(+)-ATPase activity by up to 67 %. In contrast, 12-HPETE
      and 15-HPETE did not inhibit Na+, K(+)-ATPase activity. In addition, neither 5
      HETE or LTA4 inhibited Na+, K(+)-ATPase activity. Dose-response studies indicated
      that 5-HPETE was a potent (IC25 = 10(-8) M) inhibitor of Na+, K(+)-ATPase
      activity. These findings indicate that 5-HPETE inhibits Na+, K(+)-ATPase activity
      by a mechanism that is dependent on the hydroperoxide position and independent of
      further metabolism by 5-lipoxygenase. It is proposed that 5-HPETE production by 5
      lipoxygenase and subsequent inhibition of neuronal Na+, K(+)-ATPase activity may
      be a mechansim for modulating synaptic transmission.

PMID- 9199201
TI  - Photoaffinity labeling of yeast farnesyl protein transferase and enzymatic
      synthesis of a Ras protein incorporating a photoactive isoprenoid.
AB  - Farnesyl protein transferase (FPTase) catalyzes the covalent attachment of a
      farnesyl (C15) group from farnesyl pyrophosphate (FPP) to a specific cysteine
      residue of Ras and several other proteins. In this report, photoactive farnesyl
      and geranylgeranyl pyrophosphate analogs 2-diazo-3,3,3-trifluoropropionyloxy
      geranyl pyrophosphate (DATFP-GPP) and 2-diazo-3,3,3-trifluoropropionyloxy
      farnesyl pyrophosphate (DATFP-FPP) were used to study the active site of
      Saccharomyces cerevisiae FPTase. Both analogs are substrates for the enzyme, and
      upon irradiation, DATFP-GPP inhibits FPTase activity in a time-dependent manner.
      Photoinactivation by DATFP-GPP is prevented by the presence of the natural
      substrate FPP. Photolysis of radiolabeled DATFP-GPP results in preferential
      labeling of the beta subunit of FPTase, suggesting that this subunit is involved
      in recognition of FPP. Of particular importance, DATFP-GPP and DATFP-FPP were
      used to enzymatically transfer the photoactive isoprenoid moieties to peptides
      and to Ras; such molecules should be useful for identifying cellular components
      which specifically recognize farnesylated Ras and other prenylated proteins.

PMID- 9199202
TI  - Inhibition of Grb2 and Crkl proteins results in growth inhibition of Philadelphia
      chromosome positive leukemic cells.
AB  - The Bcr-Abl oncoprotein is necessary for the growth of Philadelphia chromosome
      positive (Ph+) leukemic cells. The Bcr-Abl protein has been found to bind to
      SH2/SH3-containing adaptor proteins such as Grb2 and Crkl, and these complexes
      are believed to activate various signaling pathways. Grb2 and Crkl are important
      for the Bcr-Abl-mediated transformation of rat fibroblasts and murine
      hematopoietic cells. We have used liposomes to deliver nuclease-resistant
      antisense oligonucleotides (oligos) that are specific for the GRB2 or CRKL mRNA
      to leukemic cells to specifically downregulate Grb2 or Crkl protein expression.
      We found that by downregulating Grb2 or Crkl protein expression, Grb2 or Crkl
      antisense oligos could selectively inhibit the growth of Bcr-Abl positive cells,
      but not that of Bcr-Abl negative cells. Our data, together with other
      investigators' data, strongly indicate that Grb2 and Crkl are vital for the
      maintenance of cell growth in Ph+ leukemias.

PMID- 9199203
TI  - Insulin-like growth factor I induces tumor hexokinase RNA expression in cancer
      cells.
AB  - Increased glycolysis is a characteristic of cancer cells. Though less efficient
      in energy production, it ensures continuous supply of energy and
      phosphometabolites for biosynthesis enabling metastatic and less vascularized
      cancer cells to proliferate even under hypoxic conditions. Since hexokinase is
      the first rate limiting enzyme in the glycolytic pathway, elevated levels of Type
      II like hexokinase in tumors are of great significance in this context. Under
      normal conditions insulin regulates expression of hexokinase Type II isoenzyme,
      which is predominantly expressed in muscle. On the other hand cancer cells
      overexpress insulin-like growth factors and their receptors which mimic many
      activities of insulin. This prompted us to examine a hypothesis that insulin-like
      growth factors may be responsible for overexpression of tumor hexokinase. Our
      experiments demonstrate that insulin-like growth factor I indeed induces
      hexokinase gene expression in a concentration and time dependent manner in two
      cancer cell lines we studied.

PMID- 9199204
TI  - Regulation of cytokine-induced iNOS expression by a hairpin oligonucleotide in
      murine cerebral endothelial cells.
AB  - Inducible nitric oxide synthase (iNOS) is expressed in response to cytokines by a
      number of cell types participating in CNS inflammation, including brain cerebral
      endothelial cells. NF-kappaB, a transcription factor, mediates effector actions
      of pro-inflammatory cytokines. A combination of tumor necrosis factor alpha (TNF
      alpha) and interferon gamma (IFN-gamma) enhanced the expression of iNOS in murine
      cerebral endothelial cells (MCECs). In an attempt to modulate TNF-alpha+IFN-gamma
      induced expression of iNOS in MCECs, we designed a double-strand hairpin (hp)
      oligonucleotide carrying the NF-kappaB motif. This hp oligonucleotide inhibited
      NF-kappaB binding activity and decreased both iNOS mRNA and protein expression
      induced by TNF-alpha+IFN-gamma. As a control, a mutant hp oligonucleotide was
      without effect. The present study confirms the role of transcription factor NF
      kappaB in iNOS expression induced by TNF-alpha+IFN-gamma in MCECs. More
      importantly, it demonstrates that an appropriately designed hp oligonucleotide is
      an effective tool to modulate iNOS expression and may be of potential
      pharmacological use.

PMID- 9199205
TI  - Identification of serine 380 as the major site of autophosphorylation of Xenopus
      pp90rsk.
AB  - Rsk is a 90-kDa protein kinase that is activated by phosphorylation by MAP kinase
      at the end of a well-established signaling cascade. Rsk has two conserved
      catalytic kinase domains. The amino terminal kinase domain is responsible for
      phosphorylation of exogenous substrates. The carboxyl terminal domain of rsk has
      a basal autophosphorylation activity which can be detected when recombinant
      protein is incubated with [gamma-32P]ATP. The manner in which rsk activity is
      controlled by site specific phosphorylation is largely unknown. We show that rsk
      can autophosphorylate through an intermolecular mechanism. Autophosphorylation
      occurs primarily on serine 380, in a highly conserved region of rsk between its
      two kinase domains. That site of autophosphorylation is similar to sites found in
      other serine/threonine kinases, which are also regulated by phosphorylation at
      that corresponding site. The carboxyl terminal kinase domain of rsk becomes a
      potential candidate kinase involved in phosphorylating and regulating the
      activity of those other kinases through their conserved domains.

PMID- 9199206
TI  - CpG methylation inactivates the transcriptional activity of the promoter of the
      human p53 tumor suppressor gene.
AB  - Alterations of the methylation patterns of DNA are common in cancer cells and
      could conceivably comprise a subset of causal events in the carcinogenesis
      process. Although it has previously been shown that methylation of CpG islands in
      the 5'-control regions of tumor suppressor genes such as p16, Von Hippel-Lindau
      (VHL) syndrome gene, and the retinoblastoma (RB) gene can suppress expression and
      function of these gene products, the elements that control the expression of the
      p53 gene have not been examined in detail. In this study we examined the effect
      of CpG methylation in a region of the p53 promoter containing major transcription
      start sites. A region of the p53 promoter (from -199 to +142) containing 15 CpG
      dinucleotides was placed in a pCAT reporter plasmid and reporter activity was
      assessed in host CV-1 cells. We show for the first time that transcriptional
      activation of the p53 tumor suppressor gene, as assessed by a reporter plasmid
      construct, can be down-regulated by cytosine methylation in the basal promoter
      region. We believe these data suggest a role for methylation of CpG sequences in
      the regulation of transcription of p53. This implies that the tumor suppressor
      gene p53 could, therefore, contribute to carcinogenesis by inactivation via
      methylation of a key element in cell cycle control.

PMID- 9199207
TI  - Molecular cloning of a 1alpha,25-dihydroxyvitamin D3-inducible transcript (DDVit
      1) in human blood monocytes.
AB  - The differentiation and activation of monocytes (MO) and monocytic cells is
      modulated by 1alpha,25-dihydroxyvitamin D3 (Vitamin D3). In order to investigate
      early effects on the differentiation process of MO, we used the mRNA Differential
      Display technology to identify genes that are induced in freshly isolated human
      blood MO cultured for 4 hours with Vitamin D3. A cDNA fragment was isolated and
      Northern analysis confirmed a low expression of this cDNA at about 1,4 kb in MO
      which was increased by the addition of Vitamin D3. Using the rapid amplification
      of cDNA Ends (RACE)-PCR we got a transcript (DDVit 1) of a length of 1251 bp
      containing an open reading frame that encodes a putative 16,5 kD protein.
      Database search revealed an identity with a possible enterocyte differentiation
      promoting factor with a length of 1177 bp that has not been further
      characterized. Therefore DDVit 1 may be a differentiation promoting factor for
      the monocytic lineage. Further investigations will clarify the role of this
      protein in the differentiation process of MO.

PMID- 9199208
TI  - Biglycan gene promoter activity in osteosarcoma cells is regulated by cyclic AMP.
AB  - The pericellular proteoglycan biglycan is among the major secretory products of
      osteoblasts and articular chondrocytes but the regulatory agents and signal
      transduction pathways that ultimately lead to alterations in biglycan gene
      expression are poorly defined. We report here on the transcriptional up
      regulation of biglycan in MG-63 osteosarcoma cells by agents that increase
      intracellular cAMP levels. Transfection of these cells with biglycan promoter
      luciferase reporter fusion genes and subsequent treatment with forskolin or the
      cAMP analog 8-Bromo-cAMP resulted in an up to 3.8-fold stimulation of biglycan
      promoter activity. This effect could be prevented with the compound KT5720, a
      specific inhibitor of the cAMP-dependent protein kinase. Up-regulation of
      transcription is also reflected at the level of mRNA expression, since biglycan
      mRNA steady state levels in MG-63 cells increased approximately 2-fold after 24
      hours of forskolin treatment. These data suggest that elevated levels of
      intracellular cAMP increase transcription from the biglycan promoter in bone
      cells and implicate for the first time the cAMP/protein kinase A signal
      transduction pathway in the regulation of biglycan gene expression.

PMID- 9199209
TI  - Arachidonic acid stimulates prostate cancer cell growth: critical role of 5
      lipoxygenase.
AB  - Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-6 poly
      unsaturated fatty acids, was found to be an effective stimulator of human
      prostate cancer cell growth in vitro at micromolar concentrations. Selective
      blockade of the different metabolic pathways of arachidonic acid (e.g. ibuprofen
      for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12
      lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth
      stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase
      specific inhibitors, AA861 and MK886, but not by others. Addition of the
      eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of
      prostate cancer cell growth similar to that of arachidonic acid, whereas the
      leukotrienes were ineffective. Moreover, the 5-series of eicosatetraenoids could
      reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed
      with arachidonic acid showed a dramatic increase in the production of 5-HETEs
      which is effectively blocked by MK886. These experimental observations suggest
      that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway
      to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects
      on human prostate cancer cells.

PMID- 9199210
TI  - Active site architecture of polymorphic forms of human glutathione S-transferase
      P1-1 accounts for their enantioselectivity and disparate activity in the
      glutathione conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-ox y-7,8,9,10
      tetrahydrobenzo(a)pyrene.
AB  - In this study, we demonstrate that the active site architecture of the human
      glutathione (GSH) S-transferase Pi (GSTP1-1) accounts for its enantioselectivity
      in the GSH conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9, 10
      tetrahydrobenzo(a) pyrene (anti-BPDE), the ultimate carcinogen of benzo(a)pyrene.
      Furthermore, we report that the two polymorphic forms of human GSTP1-1, differing
      in their primary structure by a single amino acid in position 104, have disparate
      activity toward (+)-anti-BPDE, which can also be rationalized in terms of their
      active site structures. When concentration of (+)-anti-BPDE, which among four
      BPDE isomers is the most potent carcinogen, was varied and GSH concentration was
      kept constant at 2 mM (saturating concentration), both forms of hGSTP1-1 [hGSTP1
      1(V104) and hGSTP1-1(I104)] obeyed Michaelis-Menten kinetics. The V(max) of GSH
      conjugation of (+)-anti-BPDE was approximately 3.4-fold higher for hGSTP1-1(V104)
      than for hGSTP1-1(I104). Adherence to Michaelis-Menten kinetics was also observed
      for both isoforms when (-)-anti-BPDE, which is a weak carcinogen, was used as the
      variable substrate. However, (-)-anti-BPDE was a relatively poor substrate for
      both isoforms as compared with (+)-anti-BPDE. Moreover, there were no significant
      differences between hGSTP1-1(V104) and hGSTP1-1(I104) in either V(max) or K(m)
      for (-)-anti-BPDE. The mechanism of differences in kinetic properties and
      enantioselectivity of hGSTP1-1 variants toward anti-BPDE was investigated by
      modeling of the two proteins with conjugation product molecules in their active
      sites. Molecular modeling studies revealed that the differences in catalytic
      properties of hGSTP1-1 variants as well as the enantioselectivity of hGSTP1-1 in
      the GSH conjugation of anti-BPDE can be rationalized in terms of the architecture
      of their active sites. Our results suggest that the population polymorphism of
      hGSTP1-1 variants with disparate enzyme activities may, at least in part, account
      for the differential susceptibility of individuals to carcinogens such as anti
      BPDE and possibly other similar carcinogens.

PMID- 9199211
TI  - A calcium-dependent nitric oxide synthase and NMDA R1 glutamate receptor in the
      ink gland of Sepia officinalis: a hint to a regulatory role of nitric oxide in
      melanogenesis?
AB  - Histochemical, immunohistochemical, and biochemical evidence is reported showing
      that the ink gland of the cuttlefish Sepia officinalis contains a calcium
      dependent isoform of nitric oxide synthase as well as an NMDA R1 receptor subunit
      localized for the most part in the immature inner cells of the epithelial layer
      of the gland. These results may be taken to implicate a hitherto unrecognized
      regulatory role of the glutamate-nitric oxide pathway in the maturation and
      metabolic activity of melanin-producing cells in the cephalopod defense system.

PMID- 9199212
TI  - D-aspartic acid localization during postnatal development of rat adrenal gland.
AB  - Developmental changes in cellular localization of D-aspartic acid (D-Asp) were
      investigated in rat adrenal gland with polyclonal anti-D-Asp antibody. At 1 and 3
      weeks of age, immunoreactivity (IR) toward this amino acid was intense in the
      cytoplasm of cells in the zona fasciculata (ZF) and zona reticularis (ZR) of the
      adrenal cortex but was less so in the zona glomerulosa (ZG). Conversely at 8
      weeks of age, intense IR was observed in the ZG and less in the ZF and ZR. In the
      adrenal medulla, IR was evident in large clusters of cells which were identified
      as adrenaline-storing cells. The emergence of D-Asp in specific types of cells at
      distinct periods of development of rat adrenal gland suggests that this amino
      acid may have a physiological role in the maturation of the organ.

PMID- 9199213
TI  - Expression of members of the novel membrane linked metalloproteinase family ADAM
      in cells derived from a range of haematological malignancies.
AB  - ADAMs (A disintegrin and metalloproteinase) are a recently discovered family of
      proteins with significant primary sequence similarity to the reprolysin family of
      snake venomases. These ADAMs closest known homologues are the type III reprolysin
      enzymes which have been demonstrated to be, among other things potent type IV
      collagenases. ADAMs are putative membrane linked proteins with several domains
      including a metalloproteinase domain, a potential integrin binding domain, a
      cysteine rich sequence and an EGF like sequence. They have been implicated in a
      wide variety of functions including basement membrane degradation and cell-cell
      and cell-matrix interactions. We have used RT-PCR and Northern blotting to
      characterise the expression of members of this family in cells derived from a
      variety of haematological malignancies including leukaemia (HL60 and Jurkat),
      erythroleukaemia (K562), lymphoma (U937 and Cupillo) and myeloma (U266B1). We
      find clear expression of four members of this novel family of proteins but note
      differences in the expression levels of each member. The ADAMs known as MADM
      (ADAM10), MCMP (ADAM12, MDC9) and Metargidin (ADAM15) which all possess
      potentially active metalloproteinase domains are expressed in all these cell
      types to significant levels. The putative tumour suppressor gene MDC (ADAM11) is
      expressed at very low levels in all cells examined. As ADAMs may have both
      potential metalloproteinase activity and adhesive domains we wish to explore the
      role of these proteins with regard to pathophysiology of haematological
      malignancy such as egression of leukaemic cells from the bone marrow.

PMID- 9199214
TI  - A brief history of people and events related to atomic weapons testing in the
      Marshall Islands.
AB  - The events related to nuclear testing in the Marshall Islands began at the end of
      WWII when the U.S. began an initiative to determine the effect of nuclear weapons
      on naval vessels and on the performance of military personnel. The first tests
      took place in 1946 even though the area known as Micronesia was not entrusted to
      the U.S. by the United Nations until 1947. Beginning with the first relocation of
      the Bikini people to Rongerik Atoll in 1946, the saga of the Marshall Islands
      involvement in the atomic age began. Although the testing program was limited to
      the years 1946 through 1958, many of the consequences and events related to the
      testing program continued over the decades since. That story is still ongoing
      with programs currently underway to attempt to resettle previously displaced
      communities, remediate contaminated islands, and to settle claims of damages to
      individuals and communities. The history of the years subsequent to 1958 are a
      mixed chronicle of a few original scientific investigations aimed at
      understanding the coral atoll environment, continued surveillance of the acutely
      exposed Marshallese, some efforts at cleanup and remediation, numerous monitoring
      programs and many studies repeated either for credibility purposes, to satisfy
      international demands or because the changing state of knowledge of radiation
      protection has necessitated us to rethink earlier beliefs and conclusions about
      late health effects and social consequences. The objective of this paper is to
      briefly note many of the historical and political events, scientific studies,
      persons and publications from 1946 to the present that relate to atomic weapons
      testing in the Marshall Islands.

PMID- 9199215
TI  - Monitoring distant fallout: the role of the Atomic Energy Commission Health and
      Safety Laboratory during the Pacific tests, with special attention to the events
      following BRAVO.
AB  - The fallout from test BRAVO in March 1954 has had scientific, political, and
      social implications that have continued for more than 40 years. The test resulted
      in serious injury to the people of the Marshall Islands and 23 men on a nearby
      Japanese fishing boat. Prior to BRAVO there was insufficient appreciation of the
      dangers of fallout to people living downwind from surface or near-surface
      explosions of megaton weapons. In the absence of sufficient preplanning for
      fallout monitoring beyond the test-sites of earlier smaller yield tests, and as a
      result of the concern of the photographic film manufacturers, the Atomic Energy
      Commission Health and Safety Laboratory, now the Department of Energy
      Environmental Measurements Laboratory, was requested to develop a program of
      fallout surveillance. Beginning with Operation IVY in 1952, these surveys
      included aerial monitoring of the islands of the mid and western Pacific, as well
      as establishment of fallout monitoring stations in the United States and abroad.
      The first evidence of the post-BRAVO fallout was detected by a Atomic Energy
      Commission Health and Safety Laboratory instrument installed on the atoll of
      Rongerik, where 28 military personnel were stationed. The results of radiation
      surveys conducted immediately after BRAVO, as well as the reports of medical
      investigations, radioecological studies, and dose reconstruction that have been
      conducted by many laboratories over the years have been available from the
      beginning in unclassified form. However, from the time of the fallout, and
      continuing to the present, there have been many unanswered questions about what
      happened during the hours immediately after the fallout was reported. No formal
      investigation of the circumstances of the fallout was ever conducted, and there
      were serious misrepresentations of the facts in the official statements made at
      the time.

PMID- 9199216
TI  - A history of the people of Bikini following nuclear weapons testing in the
      Marshall Islands: with recollections and views of elders of Bikini Atoll.
AB  - The people of Bikini Atoll were moved from their homeland in 1946 to make way for
      the testing of 23 nuclear weapons by the United States government, beginning with
      the world's fourth atomic detonation. The subsequent half-century exodus of the
      Bikini people included a 2-y stay on Rongerik Atoll, where near starvation
      resulted, and a 6-mo sojourn on Kwajalein Atoll, where they lived in tents beside
      a runway used by the U.S. military. In 1948, they were finally relocated to Kili,
      a small, isolated, 200-acre island owned by the U.S. Trust Territory government.
      Numerous hardships have been faced there, not the least of which was the loss of
      skills required for self-sustenance. Located 425 miles south of Bikini, Kili
      Island is without a sheltered lagoon. Thus for six months of the year, fishing
      and sailing become futile endeavors. Because of the residual radioactive
      contamination from the nuclear testing, the majority of the Bikinian population
      still resides on Kili today. One attempt was made to resettle Bikini in the late
      1960's when President Lyndon B. Johnson, on recommendations from the Atomic
      Energy Commission, declared Bikini Atoll safe for habitation. In 1978, however,
      it was discovered by the U.S. Department of Energy that in the span of only one
      year, some of the returned islanders were showing a 75% increase in their body
      burdens of 137Cs. In 1978, the people residing on Bikini were moved again, this
      time to a small island in Majuro Atoll. In the early 1980's, the Bikinians filed
      a class action lawsuit against the U.S. government for damages arising out of the
      nuclear testing program. Although the claim was dismissed, eventually a $90
      million trust fund was established for their local government. Since then the
      leaders of the people of Bikini residing on Kili Island and Majuro Atoll have
      been confronted with the immense responsibility of determining how to clean their
      atoll while at the same time maintaining the health and welfare of their
      displaced population. For the community and their leaders, grappling with these
      technical decisions has created a life of strife, debate and conflict-and an
      uncertain future. Now, a radiological cleanup of Bikini is expected to begin
      sometime within 1997. The objective of this paper, with the support of the views
      and the recollections of elder Bikinians, is to recount the history and discuss
      issues facing the first displaced people of the nuclear age.

PMID- 9199217
TI  - The Northern Marshall Islands Radiological Survey: data and dose assessments.
AB  - Fallout from atmospheric nuclear tests, especially from those conducted at the
      Pacific Proving Grounds between 1946 and 1958, contaminated areas of the Northern
      Marshall Islands. A radiological survey at some Northern Marshall Islands was
      conducted from September through November 1978 to evaluate the extent of residual
      radioactive contamination. The atolls included in the Northern Marshall Islands
      Radiological Survey (NMIRS) were Likiep, Ailuk, Utirik, Wotho, Ujelang, Taka,
      Rongelap, Rongerik, Bikar, Ailinginae, and Mejit and Jemo Islands. The original
      test sites, Bikini and Enewetak Atolls, were also visited on the survey. An
      aerial survey was conducted to determine the external gamma exposure rate.
      Terrestrial (soil, food crops, animals, and native vegetation), cistern and well
      water samples, and marine (sediment, seawater, fish and clams) samples were
      collected to evaluate radionuclide concentrations in the atoll environment.
      Samples were processed and analyzed for 137Cs, 90Sr, 239+240Pu and 241Am. The
      dose from the ingestion pathway was calculated using the radionuclide
      concentration data and a diet model for local food, marine, and water
      consumption. The ingestion pathway contributes 70% to 90% of the estimated dose.
      Approximately 95% of the dose is from 137Cs. 90Sr is the second most significant
      radionuclide via ingestion. External gamma exposure from 137Cs accounts for about
      10% to 30% of the dose. 239+240Pu and 241Am are the major contributors to dose
      via the inhalation pathway; however, inhalation accounts for only about 1% of the
      total estimated dose, based on surface soil levels and resuspension studies. All
      doses are computed for concentrations decay corrected to 1996. The maximum annual
      effective dose from manmade radionuclides at these atolls ranges from .02 mSv y(
      1) to 2.1 mSv y(-1). The background dose in the Marshall Islands is estimated to
      be 2.4 mSv y(-1). The combined dose from both background and bomb related
      radionuclides ranges from slightly over 2.4 mSv y(-1) to 4.5 mSv y(-1). The 50-y
      integral dose ranges from 0.5 to 65 mSv.

PMID- 9199218
TI  - Past and present levels of some radionuclides in fish from Bikini and Enewetak
      Atolls.
AB  - Bikini and Enewetak were the sites in the Northern Marshall Islands that were
      used by the United States as testing grounds for nuclear devices between 1946 and
      1958. The testing produced close-in fallout debris that was contaminated with
      different radionuclides and which entered the aquatic environment. The
      contaminated lagoon sediments became a reservoir and source term of manmade
      radionuclides for the resident marine organisms. This report contains a summary
      of all the available data on the concentrations of 137Cs, 60Co and 207Bi in flesh
      samples of reef and pelagic fish collected from Bikini and Enewetak Atolls
      between 1964 and 1995. The selection of these three radionuclides for discussion
      is based on the fact that these are the only radionuclides that have been
      routinely detected by gamma spectrometry in flesh samples from all fish for the
      last 20 y. Flesh from fish is an important source of food in the Marshallese
      diet. These radionuclides along with the transuranic radionuclides and 90Sr
      contribute most of the small radiological dose from ingesting marine foods. Some
      basic relationships among concentrations in different tissues and organs are
      discussed. The reef fish can be used as indicator species because their body
      burden is derived from feeding, over a lifetime, within a relatively small
      contaminated area of the lagoon. Therefore, the emphasis of this report is to use
      this extensive and unique concentration data base to describe the effective half
      lives and cycling for the radionuclides in the marine environments during the 31
      y period between 1964 and 1995. The results from an analysis of the radionuclide
      concentrations in the flesh samples indicate the removal rates for the 3
      radionuclides are significantly different. 137Cs is removed from the lagoons with
      an effective half life of 9-12 y. Little 60Co is mobilized to the water column so
      that it is depleted in both environments, primarily through radioactive decay.
      The properties of 207Bi are different at Enewetak and Bikini. At Enewetak the
      radionuclide is lost from the environment with an effective half live of 5.1 y.
      At Bikini only radioactive decay can account for the rate at which the
      radionuclide is lost from the lagoon. The difference in the binding properties of
      the sedimentary materials for 207Bi among the two Atolls is not understood.

PMID- 9199219
TI  - Findings of the first comprehensive radiological monitoring program of the
      Republic of the Marshall Islands.
AB  - The Marshall Islands was the primary site of the United States atomic weapons
      testing program in the Pacific. From 1946 through 1958, 66 atomic weapons were
      detonated in the island country. For several decades, monitoring was conducted by
      the U.S. Department of Energy (or its predecessor agencies) on the test site
      atolls and neighboring atolls. However, 70% of the land area of the over 1,200
      islands in the Marshall Islands was never systematically monitored prior to 1990.
      For the 5-y period from 1990 through 1994, the Government of the Republic of the
      Marshall Islands undertook an independent program to assess the radiological
      conditions throughout its 29 atolls. The scientific work was performed under the
      auspices of the Section 177 Agreement of the Compact of Free Association, U.S.
      public law 99-239, signed in 1986 by President Ronald Reagan. Although the total
      land area of the nations is a scant 180 km2, the islands are distributed over 6 x
      10(5) km2 of ocean. Consequently, logistics and instrumentation were main
      considerations, in addition to cultural and language issues. The core of the
      monitoring program was in-situ gamma spectrometry measurements made on more than
      400 islands. Native foods including coconuts and other tropical fruits were
      sampled as well as more than 200 soil profiles and more than 800 surface soil
      samples. The fruits, soil profiles and surface soil samples have been analyzed
      for all gamma emitters with an emphasis on determining concentrations of 137Cs;
      the surface soil samples were also analyzed for 239+240Pu. All measurements were
      conducted in a radiological laboratory built in the capital city of the Marshall
      Islands specifically for the purposes of this study. The program was extensively
      assisted in the field and in the laboratory by Marshallese workers. The
      interpretation of environmental radiation data in the Marshall Islands required
      thoughtful analysis because the atolls lie along a latitude and precipitation
      gradient that effected the deposition of local and global fallout. The objective
      of this paper is to report findings for all atolls of the Marshall Islands on the
      137Cs areal inventory (Bq m(-2)) and the external effective dose-rate (mSv y(
      1)), the projected internal effective dose-rate (mSv y(-1)) from an assumed diet
      model, and surface soil concentrations of 239,240Pu (Bq kg(-1)) for selected
      northern atolls. Interpretation is also provided on the degree of contamination
      above global fallout levels. This report provides the first comprehensive summary
      of the radiological conditions throughout the Marshall Islands.

PMID- 9199220
TI  - 137Cs exposure in the Marshallese populations: an assessment based on whole-body
      counting measurements (1989-1994).
AB  - The Marshall Islands were the site of numerous tests of nuclear weapons by the
      United States. From 1946 to 1958, nuclear devices were detonated at Enewetak and
      Bikini Atolls. Following the inadvertent contamination of the northern islands
      downwind of the 1954 Bravo Test, Brookhaven National Laboratory became involved
      in the medical care and the radiological safety of the affected populations. One
      important technique employed in assessing the internally deposited radionuclides
      is whole-body counting. To estimate current and future exposures to 137Cs, data
      from 1989 to 1994 were analyzed and are reported in this paper. During this
      period, 3,618 measurements were made for the Marshallese. The cesium body
      contents were assumed to result from a series of chronic intakes. Also, it was
      assumed that cesium activity in the body reaches a plateau that is maintained
      over 365 d. We estimated the annual effective dose rate for each population,
      derived from the recommendations of the International Commission on Radiological
      Protection. The average 137Cs uptake measured by the whole-body counting method
      varies from one population to another; it was consistent with measurements of
      external exposure rate. The analysis, though based on limited data, indicates
      that there is no statistical support for a seasonal effect on 137Cs uptake. The
      critical population group for cesium uptake is adult males. Within the 5-y
      monitoring period, all internal exposures to 137Cs were less than 0.2 mSv y(-1).
      Similarly, a persistent average cesium effective dose rate of 2 microSv y(-1) was
      determined for Majuro residents.

PMID- 9199221
TI  - An updated dose assessment for resettlement options at Bikini Atoll--a U.S.
      nuclear test site.
AB  - On 1 March 1954, a nuclear weapon test, code-named BRAVO, conducted at Bikini
      Atoll in the northern Marshall Islands contaminated the major residence island.
      There has been a continuing effort since 1977 to refine dose assessments for
      resettlement options at Bikini Atoll. Here we provide a radiological dose
      assessment for the main residence island, Bikini, using extensive radionuclide
      concentration data derived from analysis of food crops, ground water, cistern
      water, fish and other marine species, animals, air, and soil collected at Bikini
      Island as part of our continuing research and monitoring program that began in
      1978. The unique composition of coral soil greatly alters the relative
      contribution of 137Cs and 90Sr to the total estimated dose relative to
      expectations based on North American and European soils. Without counter
      measures, 137Cs produces 96% of the estimated dose for returning residents,
      mostly through uptake from the soil to terrestrial food crops but also from
      external gamma exposure. The doses are calculated assuming a resettlement date of
      1999. The estimated maximum annual effective dose for current island conditions
      is 4.0 mSv when imported foods, which are now an established part of the diet,
      are available. The 30-, 50-, and 70-y integral effective doses are 91 mSv, 130
      mSv, and 150 mSv, respectively. A detailed uncertainty analysis for these dose
      estimates is presented in a companion paper in this issue. We have evaluated
      various countermeasures to reduce 137Cs in food crops. Treatment with potassium
      reduces the uptake of 137Cs into food crops, and therefore the ingestion dose, to
      about 5% of pretreatment levels and has essentially no negative environmental
      consequences. We have calculated the dose for the rehabilitation scenario where
      the top 40 cm of soil is removed in the housing and village area, and the rest of
      the island is treated with potassium fertilizer; the maximum annual effective
      dose is 0.41 mSv and the 30-, 50-, and 70-y integral effective doses are 9.8 mSv,
      14 mSv, and 16 mSv, respectively.

PMID- 9199222
TI  - Uncertainty and variability in updated estimates of potential dose and risk at a
      U.S. nuclear test site--Bikini Atoll.
AB  - Uncertainty and interindividual variability were assessed in estimated doses for
      a rehabilitation scenario for Bikini Island at Bikini Atoll, in which the top 40
      cm of soil would be removed in the housing and village area, and the rest of the
      island would be treated with potassium fertilizer, prior to an assumed
      resettlement date of 1999. Doses were estimated for ingested 137Cs and 90Sr,
      external gamma-exposure, and inhalation+ingestion of 241Am + 239+240Pu. Two
      dietary scenarios were considered: imported foods are available (IA); imported
      foods are unavailable with only local foods consumed (IUA). After approximately 5
      y of Bikini residence under either IA or IUA assumptions, upper and lower 95%
      confidence limits on interindividual variability in calculated dose were
      estimated to lie within a approximately threefold factor of its in population
      average value; upper and lower 95% confidence limits on uncertainty in calculated
      dose were estimated to lie within a approximately twofold factor of its expected
      value. For reference, the expected values of population-average dose at age 70 y
      were estimated to be 16 and 52 mSv under IA and IUA dietary assumptions,
      respectively. Assuming that 200 Bikini resettlers would be exposed to local foods
      (under both IA and IUA assumptions), the maximum 1-y dose received by any Bikini
      resident is most likely to be approximately 2 and 8 mSv under the IA and IUA
      assumptions, respectively. Under the most likely dietary scenario, involving
      access to imported foods, this analysis indicates that it is most likely that no
      additional cancer fatalities (above those normally expected) would arise from the
      increased radiation exposures considered.

PMID- 9199223
TI  - Assessment of plutonium exposure in the Enewetak population by urinalysis.
AB  - Since 1980, the inhabitants of Enewetak Atoll have been monitored periodically by
      scientists from Brookhaven National Laboratory for internally deposited
      radioactive material. In 1989, the establishment of fission track analysis and of
      a protocol for shipboard collection of 24-h urine samples significantly improved
      our ability to assess the internal uptake of plutonium. The purpose of this
      report is to show the distribution of plutonium concentrations in urine collected
      in 1989 and 1991, and to assess the associated committed effective doses for the
      Enewetak population based on a long-term chronic uptake of low-level plutonium.
      To estimate dose, we derived the plutonium dose-per-unit-uptake coefficients
      based on the dosimetric system of the International Commission on Radiological
      Protection. Assuming a continuous uptake, an integrated Jones's plutonium urine
      excretion function was developed to interpret the Enewetak urine data. The
      Appendix shows how these values were derived. The committed effective doses were
      0.2 mSv, calculated from the 1991 average plutonium content in 69 urine samples.

PMID- 9199225
TI  - The use of comparative 137Cs body burden estimates from environmental data/models
      and whole body counting to evaluate diet models for the ingestion pathway.
AB  - Rongelap and Utirik Atolls were contaminated on 1 March 1954, by a U.S. nuclear
      test at Bikini Atoll code named BRAVO. The people at both atolls were removed
      from their atolls in the first few days after the detonation and were returned to
      their atolls at different times. Detailed studies have been carried out over the
      years by Lawrence Livermore National Laboratory (LLNL) to determine the
      radiological conditions at the atolls and estimate the doses to the populations.
      The contribution of each exposure pathway and radionuclide have been evaluated.
      All dose assessments show that the major potential contribution to the estimated
      dose is 137Cs uptake via the terrestrial food chain. Brookhaven National
      Laboratory (BNL) has carried out an extensive whole body counting program at both
      atolls over several years to directly measure the 137Cs body burden. Here we
      compare the estimates of the body burdens from the LLNL environmental method with
      body burdens measured by the BNL whole body counting method. The combination of
      the results from both methods is used to evaluate proposed diet models to
      establish more realistic dose assessments. Very good agreement is achieved
      between the two methods with a diet model that includes both local and imported
      foods. Other diet models greatly overestimate the body burdens (i.e., dose)
      observed by whole body counting. The upper 95% confidence limit of
      interindividual variability around the population mean value based on the
      environmental method is similar to that calculated from direct measurement by
      whole body counting. Moreover, the uncertainty in the population mean value based
      on the environmental method is in very good agreement with the whole body
      counting data. This provides additional confidence in extrapolating the estimated
      doses calculated by the environmental method to other islands and atolls.

PMID- 9199224
TI  - A comparison of independently conducted dose assessments to determine compliance
      and resettlement options for the people of Rongelap Atoll.
AB  - Rongelap Island was the home of Marshallese people numbering less than 120 in
      1954; 67 were on the island and severely exposed to radioactive fallout from an
      atomic weapons test in March of that year. Those resident on Rongelap were
      evacuated 50 h after the test, returned 3 y later, then voluntarily left their
      home island in 1985 due to their ongoing fear of radiation exposure from residual
      radioactive contamination. Following international negotiations in 1991, a
      Memorandum of Understanding (MOU) was signed in early 1992 between the Republic
      of the Marshall Islands Government, the Rongelap Atoll Local Government, the U.S.
      Department of Energy, and the U.S. Department of the Interior. In this MOU it was
      agreed that the Republic of the Marshall Islands, with the aid of the U.S.
      Department of Energy, would carry out independent dose assessments for the
      purpose of assisting and advising the Rongelap community on radiological issues
      related to a safe resettlement of Rongelap. The MOU enacted two action levels
      which were agreed to be used to establish whether mitigation should be considered
      as a condition for resettlement of Rongelap Island: (1) no individual should
      receive an annual dose in the future of 1 mSv or more, above that from natural
      background radiation, assuming that his/her diet consists of only locally
      produced foods, and (2) the total surface soil concentration of plutonium and
      other transuranic elements must be less than 629 Bq kg(-1) (averaged over the top
      5 cm). Environmental radiological data and dietary information were collected
      over two years (1992-1993) for the purpose of predicting future potential doses
      to Rongelapese who might resettle. In 1994, four independent assessments were
      reported, including one from each of the following entities: Marshall Islands
      Nationwide Radiological Study; Lawrence Livermore National Laboratory; an
      independent advisor from the United Kingdom (MCT); and a committee of the
      National Research Council. All four assessments concluded that possibly more than
      25% of the adult population could exceed the 1 mSv y(-1) dose level based on
      strict utilization of a local food diet. The purpose of this report is to
      summarize the methodology, assumptions, and findings from each of four
      assessments; to summarize the recommendations related to mitigation and
      resettlement options; to discuss unique programmatic aspects of the study; and to
      consider the implications of the findings to the future of the Rongelap people.

PMID- 9199226
TI  - Gastrointestinal absorption of plutonium by the Marshall Islanders.
AB  - The gastrointestinal absorption constant (f1) is a critical parameter in
      assessing systemic uptake following the ingestion of a radioactive material and
      in monitoring such intakes. This study addresses the latter, particularly for
      plutonium, and from environmental measurements derives an f1 value of 4 x 10(-4)
      for the Marshallese population. The uncertainty associated with the methodology
      and measurements used in this f1 value assessment is evaluated. This evaluation
      takes into account the results from 24-h urine samples and the particular
      lifestyle of the Marshallese. Plutonium intake resulting from soil consumption is
      a primary parameter in this evaluation; for this study, it was assumed to be 500
      mg d(-1). The f1 value determined here is consistent with the values in ICRP
      Publication 67 of 5x10(-4) for ages 1 to adult, and is the same as that suggested
      by the NRPB.

PMID- 9199227
TI  - Historical events associated with fallout from Bravo Shot--Operation Castle and
      25 Y of medical findings.
AB  - The events prior to Bravo Shot-Operation Castle that led to a decision not to
      evacuate the Marshallese prior to testing the thermonuclear bombs are presented
      as are the actions taken after the fallout incident in evacuating the exposed
      Marshallese and the military personnel. The initial medical effects (findings
      during first 6 wk after exposure) are briefly described and are followed by
      description of long term effects, namely, induction of one case of fatal acute
      myeloid leukemia and a large number of thyroid tumors (benign and malignant) in
      addition to hypothyroidism in adults and children and two cases of cretinism. The
      hypothyroidism and cretinism responded well to administration of oral thyroxine.
      During the first 25 y, there was also much unrest and political agitation
      initiated by exposed and unexposed Marshallese who were very unhappy as a result
      of relocation and inability to return to their homelands and feeling that all
      illness and deaths were due to the mysterious radiation, which they
      understandably did not understand. The difficulties in part were ameliorated by
      financial aid from the U.S. Congress. In view of one of us (EPC), no one agency
      or person in the U.S. Government was willing to take the responsibility for care
      of the Marshallese and its financing. The exposed and nonexposed Marshallese had
      their lifestyle changed, some of their homelands made uninhabitable for several
      years and could aptly be called "nuclear nomads," an expression coined by others.

PMID- 9199228
TI  - Mortality of veteran participants in the CROSSROADS nuclear test.
AB  - Operation CROSSROADS, conducted at Bikini Atoll in 1946, was the first post World
      War II test of nuclear weapons. Mortality experience of 40,000 military veteran
      participants in CROSSROADS was compared to that of a similar cohort of
      nonparticipating veterans. All-cause mortality of the participants was slightly
      increased over nonparticipants by 5% (p < .001). Smaller increases in participant
      mortality for all malignancies (1.4%, p = 0.26) or leukemia (2.0%, p = 0.9) were
      not statistically significant. These results do not support a hypothesis that
      radiation had increased participant cancer mortality over that of
      nonparticipants.

PMID- 9199229
TI  - Thyroid disease among the Rongelap and Utirik population--an update.
AB  - In 1954, 253 Marshallese were accidentally exposed to fallout radiation from the
      hydrogen bomb, BRAVO. The Marshall Islands Medical Program (MIMP) was established
      by the Department of Energy in 1955 to monitor and treat radiation-related
      disease pursuant to this accident. Medical teams from Brookhaven National
      Laboratory, a federal institution, regularly visit the Marshall Islands to give
      medical care to the exposed population. The most significant complication of the
      exposure has been found to be thyroid disease due to the ingestion of radioactive
      iodides from the fallout. In 1963 the first thyroid nodules were found in
      Rongelap subjects and in 1969 in Utirik. Non-neoplastic adenomatous nodules were
      associated with higher doses of radiation and neoplastic nodules developed in
      individuals receiving lower doses of radiation. Women were more susceptible to
      the development of palpable thyroid nodules than men. In 1994 the MIMP initiated
      examination of the thyroid by ultrasound to supplement the clinical examination.
      One hundred and sixty-four patients were evaluated. No significant differences
      were found in the incidence of thyroid nodules or the mean nodule count between
      the three groups of Rongelap and Utirik exposed and a comparison patient
      population. There was no significant difference in the incidence of thyroid
      nodules in males vs. females. Five exposed patients were referred for surgical
      excision of a nodule detected only by ultrasound. These ultrasound findings are
      unexpected in that females are known to have a higher incidence of thyroid
      disease than males and we expected that the incidence of ultrasound nodules would
      be higher in the exposed population.